WO2015157070A2 - Crispr/cas-related methods and compositions for treating cystic fibrosis - Google Patents

Abstract

CRISPR/CAS-related compositions and methods for treatment of Cystic Fibrosis (CF).

Description

CRISPR/CAS-RELATED METHODS AND COMPOSITIONS FOR TREATING

CYSTIC FIBROSIS

REFERENCE TO RELATED APPLICATIONS

The present application claims the benefit of U.S. Provisional Application No.

61/977,488, filed April 9, 2014, the contents of which are hereby incorporated by reference in their entirety.

FIELD OF THE INVENTION

The invention relates to CRISPR/CAS-related methods and components for editing of target nucleic acid sequence, and applications thereof in connection with Cystic Fibrosis (CF) CF-like disease.

BACKGROUND

Cystic fibrosis (CF) is an autosomal recessive, hereditary disease caused by defects in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The CFTR gene encodes a cAMP-gated channel that is involved in chloride and bicarbonate transport. It regulates sodium transport through inhibition of the epithelial sodium channel, which is encoded by the SCNN1A gene. CFTR is expressed on the apical surface of epithelial cells in the airway, gastrointestinal tract, reproductive tract, sweat glands and submucosal glands.

CF affects one in 3,500 children born in the United States. It is the most common fatal autosomal recessive disease in individuals of European descent (Tobias 2011; Essential Medical Genetics, John Wiley & Sons, ed. p. 312). There are approximately 30,000 subjects in the United States with the disease (From The Cystic Fibrosis Foundation; cff.org, accessed on 3/19/2015).

The most common mutation in the CFTR gene is a deletion of the three nucleotides encoding Phenylalanine (F) at position 508 of the CFTR protein (also sometime referred to herein as "F508del"). This mutation is the causative mutation in approximately two-thirds of CF cases. The remaining cases are caused by at least 1000 different mutations, many of which cause a less severe form of the disease.

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5535.1 Subjects having CF can present at birth or in early infancy with pancreatic insufficiency. Pancreatic dysfunction leads to malabsorption of fat and fat-soluble vitamins, which causes poor growth as well as gallstones and biliary disease. The lung manifestations of the disease can be more severe but may present slightly after pancreatic manifestations, in infancy or early childhood. Aberrant chloride and sodium transport due to decreased CFTR activity causes lowered apical surface fluid levels in the lungs, which leads to "sticky" mucous and lower airway obstruction. Subjects having CF or CF-like disease suffer from frequent infections due to inability to clear mucous. Local inflammatory mediators try to clear the infection but have difficulty. The triad of inflammation, infection and obstruction leads to progressive destruction of the lung parenchyma. Eventually, many subjects having CF or CF-like disease die in their late 30' s due to respiratory failure.

Current treatments for CF or CF-like disease delay lung destruction and slow disease progression. Treatments for the pulmonary manifestations of CF or CF-like disease include: antibiotics (oral, inhaled and intravenous), CFTR modulators (including CFTR potentiators), DNase, chest physiotherapy to loosen secretions and anti-inflammatory therapeutics. Treatment of the gastrointestinal manifestations includes supplemental gut soluble vitamins, high calorie diet and oral pancreatic enzymes. Subjects who develop diabetes are treated with insulin injections or an insulin pump. At the end stage, patients may benefit from lung transplant. Lung transplant may be combined with liver and/or pancreatic transplant.

Current treatments do not reverse the damage to the lungs or cure CF or CF-like disease.

The average life expectancy for subjects having CF or CF-like disease is 37 years of age

(MacKenzie et al, 2014; Annals of Internal Medicine 161(4):233-41). 80% of patients with CF or CF-like disease die from end-stage lung disease.

In spite of current therapies, there is a need for a therapy that prevents or delays the progression of disease in CF or CF-like disease.

SUMMARY OF THE INVENTION

Methods and compositions discussed herein provide for the treatment and prevention of Cystic Fibrosis (CF) and CF-like disease. The approach described herein aims to restore CFTR channel function, restore chloride, bicarbonate and/or sodium balance, and/or decrease mucous viscosity within the lungs, airways, gastrointestinal tract and reproductive tract.

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5535.1 CFTR modulators (both approved and in development) improve the functioning of mutant CFTR. These therapeutics improve CFTR functioning but do not return functionality to wild type levels. The approach described herein is expected to restore CFTR function through complete correction of the gene.

Gene therapy approaches are in development that deliver the CFTR channel gene to the lungs of CF or CF-like disease patients. However, gene therapy may require constant readministration over the course of the lifetime of a subject due to high cell turnover in target epithelial cells. The approach described herein is expected to restore CFTR function and/or ameliorate SCNN1A disinhibition permanently through one, two or several doses.

The CFTR gene encodes a 180-kDA cAMP-gated chloride (C1-) channel. The channel has six transmembrane spanning domains and is expressed by epithelial cells, lymphocytes and cardiac myocytes. The CFTR regulates the viscosity of mucous through its activity in the epithelial cells of the lungs, gastrointestinal tract and reproductive tract. Mutations in the CFTR result in decreased CFTR activity. Decreased CFTR activity can lead to aberrant ion transport, which gives rise to various disease symptoms in the lungs and other tissues, such as

accumulation of sticky mucus, airway obstruction, infection and inflammation. Correction of CFTR mutations will ameliorate or cure lung, gastrointestinal and/or reproductive symptoms of CF or CF-like disease.

The SCNN1A gene encodes the alpha subunit of the epithelial sodium channel (ENaC). The channel, comprised of alpha, beta and gamma subunits, regulates sodium transport into epithelial cells, including the epithelium of the lungs, sweat glands and kidneys. Mutations in the SCNN1A gene, (e.g. Vail 14ILE) have been shown to cause CF-like disease, characterized by pulmonary disease, including bronchiectasis. Mutations in SCNN1A also cause

pseudohypoaldosteronism, a severe disease of the kidney. Pseudohypoaldosteronism is due to defective sodium transport within kidney epithelial cells; it is not caused by defective sodium transport in other tissues. The methods described herein include the targeted knockout of SCNN1A in the lung, gastrointestinal tract and/or reproductive tract. The methods described herein will not target kidney epithelium and will avoid the negative consequences of SCNN1A mutations within the kidney epithelium. One mutation in the SCNN1A gene, a 1477T>G substitution (W493R) has been identified in subjects who also have a mutation in CFTR. This mutation is associated with a severe CF or CF-like disease phenotype, including severe

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5535.1 bronchiectasis, chronic bronchitis and/or severe gastrointestinal symptoms. This mutation has been found to be associated with 4-fold overactivity of the ENaC channel (Azad et al., 2009; Human Mutation 30: 1093-1103). Overactivity of the SCNNlA-encoded ENaC channel can contribute to CF and CF-like disease. In all subjects, the CFTR is involved in inhibition of ENaC. CFTR mutations in subjects with CF or CF-like disease leads to ENaC disinhibition, leading to overactivity of the ENaC channel. ENaC overactivity can lead to further reduction in viscosity of mucous in CF or CF-like disease subjects, as more sodium is absorbed at the apical surface of epithelial cells, followed by increased fluid absorption from the mucous layer within the lung (Baker et al., 2012; Medicine & Science in Sports and Exercise 44(12): 2315-2321). Increased fluid absorption from the mucous layer reduces mucous viscosity. Inhibition of ENaC through SCNN1A knockout and/or knockdown in subjects with CF or CF-like disease can ameliorate the symptoms of CF or CF-like disease. Mutations in the CFTR gene (also known as ABC35, ATP-binding cassette sub-family C, member 7, CFTR/MRP, dJ760C5.1 , MRP 7 and TNR-CFTR) have been shown to cause CF and/or CF-like disease. Mutations in the CFTR gene leading to CF and/or CF-like disease can be described based on their target position in the CFTR protein. In an embodiment, the target position is F508, e.g., F508del (also sometimes referred to herein as "AF508"), in the CFTR protein, which corresponds to a deletion of three nucleotides c.l521_1523delCTT in the CFTR gene (e.g., c.l521_1523delCTT (p.Phe508delPhe)). In an embodiment, the target position is G551, e.g., G551D, in the CFTR protein, which corresponds to c. l652G>A in the CFTR gene. In an embodiment, the target position is G542, e.g., G542X, in the CFTR protein, which corresponds to c. l624G>T in the CFTR gene. In an embodiment, the target position is N1303, e.g., N1303K, in the CFTR protein, which corresponds to c.3909C>G in the CFTR gene. In an embodiment, the target position is Rl 17, e.g., Rl 17H, in the CFTR protein, which corresponds to c.350G>A in the CFTR gene. In an embodiment, the target position is W1282, e.g., W1282X, in the CFTR protein, which corresponds to c. c.3846G>A in the CFTR gene. In an embodiment, the target position is R553, e.g., R553X, in the CFTR protein, which corresponds to c.l657C>T in the CFTR gene. In an embodiment, the target position is c.3717+12191, also known as c.3849+10kb, which corresponds to 3717+12191C>T in the CFTR gene. In an embodiment, the target position is c.2657+5, also known as c.2789+5, which corresponds to 2657+5G>A in the CFTR gene. In an embodiment, the target position is c.3140-26, also known as c.3272-26, which corresponds to c.3140-26A>G in the CFTR gene.

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5535.1 Overactivity of the SCNNIA gene has been shown to contribute to bronchiectasis, bronchitis, and gastrointestinal symptoms in subjects with CF and in subjects with CF-like disease. In another aspect, methods and compositions discussed herein may be used to alter the SCNNIA gene (also known as sodium channel, non-voltage-gated 1 alpha subunit; amiloride- sensitive epithelial sodium channel alpha subunit; BESC2; ENaCa; SCNEA; SCNN1;

ENaCalpha) to treat or prevent CF or CF-like disease, by targeting the SCNNIA gene, e.g., the non-coding or coding regions, e.g., a promoter region, or a transcribed sequence, e.g., intronic or exonic sequence. In an embodiment, the target position is VI 14, which corresponds to VI 141 in the SCNNIA gene. SCNNIA encodes an epithelial sodium channel, ENaC, that is negatively regulated by CFTR. In subjects with CFTR mutations, knocking out or knocking down the SCNNIA gene in certain cells will reduce or reverse the effect of defective CFTR. In subjects with no CFTR mutations but CF-like disease caused by SCNNIA mutations or other mechanisms, knocking out or knocking down the SCNNIA gene in certain cells will improve the viscosity of mucous and ameliorate disease.

Methods and compositions disclosed herein provide a number of approaches for treating or preventing CF and/or CF-like disease. As is discussed in more detail below, methods described herein provide for treating or preventing CF or CF-like disease by correcting a target position in the CFTR gene to provide corrected, or functional, e.g., wild type, CFTR. Other methods described herein allow for treating or preventing CF or CF-like disease by inducing or introducing a mutation that reduces the level of functional SCNNIA gene product.

In one aspect, methods and compositions discussed herein, provide for the correction of the underlying cause of CF or CF-like disease, e.g., the correction of a mutation at a target position in the CFTR gene, e.g., correction of a mutation in the CFTR gene that corresponds to amino acid position 508, e.g., an F508 deletion (F508del), in CFTR protein.

"CF target mutant position", as used herein, refers to a target position in the CFTR gene, which, if mutated, can result in a mutant protein and give rise to CF or CF-like disease. In an embodiment, the target position comprises one, two, or three nucleotides. In an embodiment, the CF target mutant position is a position in the CFTR gene at which a change can give rise to a mutant protein having a mutation at F508, e.g., F508del. In an embodiment, the CF target mutant position is a position in the CFTR gene at which a change can give rise to a mutant protein having a mutation at G551, e.g., G551D. In an embodiment, the CF target mutant

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5535.1 position is a position in the CFTR gene at which a change can give rise to a mutant protein having a mutation at G542, e.g., G542X, in the CFTR protein, which corresponds to c. l624G>T in the CFTR gene. In an embodiment, the CF target mutant position is a position in the CFTR gene at which a change can give rise to a mutant protein having a mutation at N1303, e.g., N1303K, in the CFTR protein, which corresponds to c.3909C>G in the CFTR gene. In an embodiment, the CF target mutant position is a position in the CFTR gene at which a change can give rise to a mutant protein having a mutation at Rl 17, e.g., Rl 17H, in the CFTR protein, which corresponds to c.350G>A in the CFTR gene. In an embodiment, the CF target mutant position is a position in the CFTR gene at which a change can give rise to a mutant protein having a mutation at W1282, e.g., W1282X, in the CFTR protein, which corresponds to c. c.3846G>A in the CFTR gene. In an embodiment, the CF target mutant position is a position in the CFTR gene at which a change can give rise to a mutant protein having a mutation at R553, e.g., R553X, in the CFTR protein, which corresponds to c. l657C>T in the CFTR gene. In an embodiment, the CF target mutant position is c.3717+12191, also known as c.3849+10kb, which corresponds to 3717+12191C>T in the CFTR gene. In an embodiment, the CF target mutant position is c.2657+5, also known as c.2789+5, which corresponds to 2657+5G>A in the CFTR gene. In an embodiment, the CF target mutant position is c.3140-26, also known as c.3272-26, which corresponds to c.3140-26 A>G in the CFTR gene. In an embodiment, the CF target mutant position is a position in the SCNN1A gene at which a change can give rise to a mutant protein having a mutation at VI 14, which corresponds to VI 141 in the SCNN1A gene.

While some of the disclosure herein is presented in the context of the mutation in the CFTR gene that gives rise to an F508 mutant protein (e.g., a F508del mutant protein) ,a G551 mutant protein (e.g., a G551D mutant protein), a G542 mutant protein (e.g., G542X mutant protein), a N1303 mutant protein (e.g., a N1303K mutant protein), a Rl 17 mutant protein (e.g., an Rl 17H mutant protein), a W1282 mutant protein (e.g., a W1282X mutant protein), an R553 mutant protein (e.g., an R553X mutant protein), a c.2789+5bp intronic mutant (e.g., a c.2789+5bp G>A mutant), or a c.3272-26bp intronic mutant (e.g., a c.3272-26bp A>G mutant), the methods and compositions herein are broadly applicable to any mutation, e.g., a point mutation or a deletion, in the CFTR gene that gives rise to CF or CF-like disease.

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5535.1 While not wishing to be bound by theory, it is believed that, in an embodiment, a mutation at a CF target mutant position is corrected by homology directed repair (HDR), as described herein.

In another aspect, methods and compositions discussed herein may be used to alter the SCNNIA gene (also known as sodium channel, non-voltage-gated 1 alpha subunit) to treat or prevent CF or CF-like disease, by targeting the SCNNIA gene, e.g., the non-coding or coding regions, e.g., a promoter region, or a transcribed sequence, e.g., intronic or exonic sequence. SCNNIA encodes an epithelial sodium channel that is negatively regulated by CFTR. By knocking out the SCNNIA gene in certain cells, the effect of defective CFTR can be reduced or reversed.

In another aspect, the methods and compositions discussed herein may be used to alter the SCNNIA gene to treat or prevent CF or CF-like disease by targeting the coding sequence of the SCNNIA gene. In one embodiment, the gene, e.g., the coding sequence of the SCNNIA gene, is targeted to knockout the gene, e.g., to eliminate expression of the gene, e.g., to knockout one or both alleles of the SCNNIA gene, e.g., by induction of an alteration comprising a deletion or mutation in the SCNNIA gene. In an embodiment, the method provides an alteration that comprises an insertion or deletion.

In an embodiment, coding region, e.g., an early coding region, of the SCNNIA gene, is targeted for alteration and knockout. In one embodiment, an early coding region of the SCNNIA gene is targeted to knockout the SCNNIA gene. In an embodiment, targeting affects both alleles of the SCNNIA gene. In an embodiment, targeting affects one allele of the SCNNIA gene. In an embodiment, a targeted knockout approach reduces or eliminates expression of functional SCNNIA gene product. In an embodiment, the method provides an alteration in the SCNNIA gene that comprises an insertion or deletion.

In another aspect, the methods and compositions discussed herein may be used to alter the SCNNIA gene to treat or prevent CF or CF-like disease by targeting non-coding sequence of the SCNNIA gene, e.g., promoter, an enhancer, an intron, 3'UTR, and/or polyadenylation signal. In an embodiment, the gene, e.g., the non-coding sequence of the SCNNIA gene, is targeted to knockout the gene, e.g., to eliminate expression of the gene, e.g., to knockout one or both alleles of the SCNNIA gene, e.g., by induction of an alteration comprising a deletion or mutation in the

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5535.1 SCNNIA gene. In an embodiment, the method provides an alteration that comprises an insertion or deletion.

As described herein, in an embodiment, a targeted knockout approach is mediated by non-homologous end joining (NHEJ) using a CRISPR/Cas system comprising an enzymatically active Cas9 (eaCas9).

"CF target knockout position", as used herein, refers to a position in the SCNNIA gene, which if altered by NHEJ-mediated alteration, results in alleviation of a symptom of CF or CF- like disease. In an embodiment, the alteration results in reduction or elimination of expression of functional SCNNIA gene product. In an embodiment, the position is in the SCNNIA coding region, e.g., an early coding region.

In an embodiment, the promoter region of the SCNNIA gene is targeted to knock down the expression of the SCNNIA gene. This type of alteration is also sometimes referred to as "knocking down" the SCNNIA gene. While not wishing to be bound by theory, in an

embodiment, a targeted knockdown approach is mediated by a CRISPR/Cas system comprising a Cas9 molecule, e.g., an enzymatically inactive Cas9 (eiCas9) molecule or an eiCas9 fusion protein (e.g., an eiCas9 fused to a transcription repressor domain or chromatin modifying protein), as described herein. In an embodiment, the SCNNIA gene is targeted to alter (e.g., to block, reduce, or decrease) the transcription of the SCNNIA gene. In another embodiment, the SCNNIA gene is targeted to alter the chromatin structure (e.g., one or more histone and/or DNA modifications) of the SCNNIA gene. In an embodiment, a CF targe knockdown position is targeted by genome editing using the CRISPR/Cas9 system. In an embodiment, one or more gRNA molecules comprising a targeting domain are configured to target an enzymatically inactive Cas9 (eiCas9) or an eiCas9 fusion protein (e.g., an eiCas9 fused to a transcription repressor domain), sufficiently close to a CF target knockdown position to reduce, decrease or repress expression of the SCNNIA gene.

"CF target knockdown position", as used herein, refers to a position in the SCNNIA gene, which if targeted, e.g., by an eiCas9 molecule or an eiCas9 fusion described herein, results in reduction or elimination of expression of functional SCNNIA gene product. In an embodiment, the transcription of the SCNNIA gene is reduced or eliminated. In another embodiment, the chromatin structure of the SCNNIA gene is altered.

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5535.1 "CF target knockin position", as used herein, refers to a sequence, which if modified by the insertion of CFTR sequence, results in an optimization of CFTR activity, e.g., by resulting in a CFTR sequence that encodes a protein having wild type activity. Exemplary CF target knockin position include: CFTR sequence within intron 2, into which, e.g., can be introduced CFTR sequence that codes for CFTR exons 3-27; and sequence within CFTR intron 10, into which sequence that codes for CFTR exons 11-27 can be introduced. In an embodiment, a CF target knockin position includes CFTR intronic sequence between a second and a third exon (e.g., intron 2), and CFTR sequence encoding the third exon through the final exon (exon 27), is introduced, resulting in a CFTR sequence that is free of one or more cryptic splice sites and that encodes a CFTR protein having wild type activity. In an embodiment, a CF target knockin position, is a position which is upstream of a mutation, or upsteam of an intron having a mutation, and introduction of wild-type CFTR sequence results in a CFTR sequence that is free of the mutation. In an embodiment the CF target knockin position is in CFTR intronic sequence: between exon2 and exon 3; or between exon 10 and exon 11. In an embodiment, the resulting CFTR sequence comprises subject sequence upstream from the CF target knockin position and newly introduced sequence downstream from the CF target knockin position, which taken together, encode a CFTR protein having wild type activity. In an embodiment, the point of insertion is 3' to a splice donor site and 5' from a splice acceptor site. In an embodiment, CFTR sequence encoding exons 3-27 is inserted under control of the promoter, e.g., at the transcription start site. In an embodiment, CFTR sequence introduced can exclude introns, e.g., a sequence encoding exons, but without introns, is inserted, e.g., CFTR CDNA sequence is introduced.

"CF target position", as used herein, refers to a CF target mutant position, CF target knockout position, CF target knockdown position, and/or CF target knockin position, as described herein.

In one aspect, disclosed herein is a gRNA molecule, e.g., an isolated or non-naturally occurring gRNA molecule, comprising a targeting domain which is complementary with a target domain from the CFTR gene or SCNNIA gene.

In an embodiment, the targeting domain of the gRNA molecule is configured to provide a cleavage event, e.g., a double strand break or a single strand break, sufficiently close to a CF target position in the CFTR gene or SCNNIA gene to allow alteration, e.g., alteration associated with, respectively, HDR or NHEJ, of a CF target position in the CFTR gene or SCNNIA gene. In

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5535.1 an embodiment, the targeting domain is configured such that a cleavage event, e.g., a double strand or single strand break, is positioned within 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 225, 250, or 300 nucleotides of a CF target position. The break, e.g., a double strand or single strand break, can be positioned upstream or downstream of a CF target position in the CFTR gene or SCNN1A gene.

In an embodiment, a second gRNA molecule comprising a second targeting domain is configured to provide a cleavage event, e.g., a double strand break or a single strand break, sufficiently close to the CF target position in the CFTR gene or SCNN1A gene, to allow alteration, e.g., alteration associated with, respectively, HDR or NHEJ, of the CF target position in the CFTR gene or SCNN1A gene, either alone or in combination with the break positioned by said first gRNA molecule. In an embodiment, the targeting domains of the first and second gRNA molecules are configured such that a cleavage event, e.g., a double strand or single strand break, is positioned, independently for each of the gRNA molecules, within 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 225, 250, or 300 nucleotides of the target position. In an embodiment, the breaks, e.g., double strand or single strand breaks, are positioned on both sides of a nucleotide of a CF target position in the CFTR gene or SCNN1A gene. In an embodiment, the breaks, e.g., double strand or single strand breaks, are positioned on one side, e.g., upstream or downstream, of a nucleotide of a CF target position in the CFTR gene or SCNN1A gene.

In an embodiment, a single strand break is accompanied by an additional single strand break, positioned by a second gRNA molecule, as discussed below. For example, the targeting domains are configured such that a cleavage event, e.g., the two single strand breaks, are positioned within 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 225, 250, or 300 nucleotides of a CF target position. In an embodiment, the first and second gRNA molecules are configured such, that when guiding a Cas9 molecule, e.g., a Cas9 nickase, a single strand break will be accompanied by an additional single strand break, positioned by a second gRNA, sufficiently close to one another to result in alteration of a CF target position in the CFTR gene or SCNN1A gene. In an embodiment, the first and second gRNA molecules are configured such that a single strand break positioned by said second gRNA is within 10, 20, 30, 40, or 50 nucleotides of the break positioned by said first gRNA molecule, e.g., when the Cas9 molecule is a nickase. In an embodiment, the two gRNA molecules are configured to position

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5535.1 cuts at the same position, or within a few nucleotides of one another, on different strands, e.g., essentially mimicking a double strand break.

In an embodiment, a double strand break can be accompanied by an additional double strand break, positioned by a second gRNA molecule, as is discussed below. For example, the targeting domain of a first gRNA molecule is configured such that a double strand break is positioned upstream of a CF target position in the CFTR gene or SCNNIA gene, e.g., within 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 225, 250, or 300 nucleotides of the target position; and the targeting domain of a second gRNA molecule is configured such that a double strand break is positioned downstream of a CF target position in the CFTR gene or SCNNIA gene, e.g., within 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 225, 250, or 300 nucleotides of the target position.

In an embodiment, a double strand break can be accompanied by two additional single strand breaks, positioned by a second gRNA molecule and a third gRNA molecule. For example, the targeting domain of a first gRNA molecule is configured such that a double strand break is positioned upstream of a CF target position in the CFTR gene or SCNNIA gene, e.g., within 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 225, 250, or 300 nucleotides of the target position; and the targeting domains of a second and third gRNA molecule are configured such that two single strand breaks are positioned downstream of a CF target position in the CFTR gene or SCNNIA gene, e.g., within 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 225, 250, or 300 nucleotides of the target position. In an embodiment, the targeting domain of the first, second and third gRNA molecules are configured such that a cleavage event, e.g., a double strand or single strand break, is positioned, independently for each of the gRNA molecules.

In an embodiment, a first and second single strand breaks can be accompanied by two additional single strand breaks positioned by a third gRNA molecule and a fourth gRNA molecule. For example, the targeting domain of a first and second gRNA molecule are configured such that two single strand breaks are positioned upstream of a CF target position in the CFTR gene or SCNNIA gene, e.g., within 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 225, 250, or 300 nucleotides of the target position; and the targeting domains of a third and fourth gRNA molecule are configured such that two single strand breaks are positioned downstream of a CF target position in the CFTR gene or SCNNIA gene, e.g.,

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5535.1 within 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 225, 250, or 300 nucleotides of the target position.

It is contemplated herein that, in an embodiment, when multiple gRNAs are used to generate (1) two single stranded breaks in close proximity, (2) two double stranded breaks, e.g., flanking a CF target position, e.g., a mutation (e.g., to remove a piece of DNA, e.g., to introduce a deletion mutation) or to create more than one indel in the gene, e.g., in a coding region, e.g., an early coding region, (3) one double stranded break and two paired nicks flanking a CF target position, e.g., a mutation (e.g., to remove a piece of DNA, e.g., to introduce a deletion mutation) or (4) four single stranded breaks, two on each side of a position, e.g., a mutation, that they are targeting the same CF target position. It is further contemplated herein that multiple gRNAs may be used to target more than one CF target position (e.g., mutation) in the same gene.

In an embodiment, the targeting domain of the first gRNA molecule and the targeting domain of the second gRNA molecules are complementary to opposite strands of the target nucleic acid molecule. In an embodiment, the gRNA molecule and the second gRNA molecule are configured such that the PAMs are oriented outward.

In an embodiment, the targeting domain of a gRNA molecule is configured to avoid unwanted target chromosome elements, such as repeat elements, e.g., Alu repeats, in the target domain. The gRNA molecule may be a first, second, third and/or fourth gRNA molecule, as described herein.

In an embodiment, the targeting domain of a gRNA molecule is configured to position a cleavage event sufficiently far from a preselected nucleotide, e.g., the nucleotide of a coding region, such that the nucleotide is not altered. In an embodiment, the targeting domain of a gRNA molecule is configured to position an intronic cleavage event sufficiently far from an intron/exon border, or naturally occurring splice signal, to avoid alteration of the exonic sequence or unwanted splicing events. The gRNA molecule may be a first, second, third and/or fourth gRNA molecule, as described herein.

In an embodiment, a CF target mutant position, e.g., a deletion in the CFTR gene, e.g., at F508, e.g., F508del, is targeted, e.g., for correction. In an embodiment, the targeting domain of a gRNA molecule comprises a sequence that is the same as, or differs by no more than 1, 2, 3, 4, or 5 nucleotides from, a targeting domain sequence from any one of Tables 1A-1E, lOA-lOC, 11A-11E or 12A-12C. In some embodiments, the targeting domain is independently selected

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5535.1 from those in Tables 1A-1E, lOA-lOC, 11A-11E or 12A-12C. For example, in certain embodiments, the targeting domain is independently selected from:

GAGGGUAAAAUUAAGCACAG (SEQ ID NO: 387);

AGUUUCUUACCUCUUCUAGU (SEQ ID NO: 388);

AAUGGUGCCAGGCAUAAUCC (SEQ ID NO: 389);

GGUAAAAUUAAGCACAG (SEQ ID NO: 390);

AGCAUGCCAACUAGAAG (SEQ ID NO: 391); or

GUAUCUAUAUUCAUCAU (SEQ ID NO: 392).

In an embodiment, when the CF target mutant position is F508, e.g., F508del, and two gRNAs are used to position two breaks, e.g., two single stranded breaks, in the target nucleic acid sequence, each guide RNA is independently selected from one of Tables 1A-1E, lOA-lOC, 11A-11E or 12A-12C.

In an embodiment, a CF target mutant position, e.g., a mutation in the CFTR gene, e.g., at G551, e.g., G551D, is targeted, e.g., for correction. In an embodiment, the targeting domain of a gRNA molecule comprises a sequence that is the same as, or differs by no more than 1, 2, 3, 4, or 5 nucleotides from, a targeting domain sequence from any one of Tables 2A-2E, 16A-16D, 17A-17E, or 18A-18C. In some embodiments, the targeting domain is independently selected from those in Tables 2A-2E, 16A-16D, 17A-17E, or 18A-18C. For example, in certain embodiments, the targeting domain is independently selected from:

GAGAAAGACAAUAUAGUUCU (SEQ ID NO: 453);

GGUGGAAUCACACUGAGUGG (SEQ ID NO: 454);

CCCACUAGCCAUAAAACCCC (SEQ ID NO: 455);

GGUGGAAUCACACUGAG (SEQ ID NO: 456);

GGAAUCACACUGAGUGG (SEQ ID NO: 457);

GGGGUUUUAUGGCUAGU (SEQ ID NO: 458); or

ACUAGCCAUAAAACCCC (SEQ ID NO: 459).

In an embodiment, more than one gRNA is used to position breaks, e.g., two single stranded breaks or two double stranded breaks, or a combination of single strand and double strand breaks, e.g., to create one or more indels, in the target nucleic acid sequence. In an embodiment, the targeting domain of each guide RNA is independently selected from one of Tables 2A-2E, 16A-16D, 17A-17E, or 18A-18C.

13

5535.1 In an embodiment, a mutation in the CFTR gene, e.g., at N1303, e.g., N1303K, is targeted, e.g., for correction. In an embodiment, the targeting domain of a gRNA molecule comprises a sequence that is the same as, or differs by no more than 1, 2, 3, 4, or 5 nucleotides from, a targeting domain sequence from any one of Tables 19A-19D, 20A-20E, or 21A-21B. In some embodiments, the targeting domain is independently selected from those in Tables 19A- 19D, 20A-20E, or 21A-21B. . For example, in certain embodiments, the targeting domain is selected from:

GGAGUGAUCAAGAAAUA (SEQ ID NO: 2223);

GAGUACCCUAACAUACC (SEQ ID NO: 2224);

GUGUGUGCACAACUUUAAAA (SEQ ID NO: 2225);

GGAAAGUUGCAGAUGAGGUA (SEQ ID NO: 2226);

GAACUUGAUGGUAAGUACAU (SEQ ID NO: 2227); or

GCUAUAUCAGCCAUUUGUGU (SEQ ID NO: 2228).

In an embodiment, when the CF target mutant position is N1303, e.g., N1303K, and two gRNAs are used to position two breaks, e.g., two single stranded breaks, in the target nucleic acid sequence, each guide RNA is independently selected from one of Tables 19A-19D, 20A- 20E, or 21A-21B.

In an embodiment, a mutation in the CFTR gene, e.g., at W1282, e.g., W1282X, is targeted, e.g., for correction. In an embodiment, the targeting domain of a gRNA molecule comprises a sequence that is the same as, or differs by no more than 1, 2, 3, 4, or 5 nucleotides from, a targeting domain sequence from any one of Tables 28A-28D, 29A-29E, or 30A-30B. In some embodiments, the targeting domain is independently selected from those in Tables 28A- 28D, 29A-29E, or 30A-30B. For example, in certain embodiments, the targeting domain is selected from:

GAAUUAUGUUUAUGGCA (SEQ ID NO: 2993);

GGAGAAAUCCAGAUCGA (SEQ ID NO: 2994);

GGCCUCUUGGGAAGAAC (SEQ ID NO: 2995);

GUCCUUUUGCUCACCUG (SEQ ID NO: 2996);

GAUCGAUGGUGUGUCUU (SEQ ID NO: 2997);

GAAGGAGAAAUCCAGAUCGA (SEQ ID NO: 2998);

GUGGGCCUCUUGGGAAGAAC (SEQ ID NO: 2999).

14

5535.1 In an embodiment, when the CF target mutant position is W1282, e.g., W1282X, and two gRNAs are used to position two breaks, e.g., two single stranded breaks, in the target nucleic acid sequence, each guide RNA is independently selected from one of Tables 28A-28D, 29A- 29E, or 30A-30B.

In an embodiment, a mutation in the CFTR gene, e.g., at R553, e.g., R553X, is targeted, e.g., for correction. In an embodiment, the targeting domain of a gRNA molecule comprises a sequence that is the same as, or differs by no more than 1, 2, 3, 4, or 5 nucleotides from, a targeting domain sequence from any one of Tables 25A-25D, 26A-26E, or 27A-27D. In some embodiments, the targeting domain is independently selected from those in Tables 25A-25D, 26A-26E, or 27A-27D. For example, in certain embodiments, the targeting domain is selected from:

GCUUUAUAUUCUGUUUC (SEQ ID NO: 466);

GGUGGAAUCACACUGAG (SEQ ID NO: 456);

GGAAUCACACUGAGUGG (SEQ ID NO: 457);

GUUCAAAAUUUCAACUG (SEQ ID NO: 464);

GGUGAAUAACUAAUUAU (SEQ ID NO: 465);

GGGGUUUUAUGGCUAGU (SEQ ID NO: 458);

GAGCAAGAAUUUCUUUAGCA (SEQ ID NO: 462);

GACAAUAUAGUUCUUGGAGA (SEQ ID NO: 460);

GAAGGUGGAAUCACACUGAG (SEQ ID NO: 461);

GGUGGAAUCACACUGAGUGG (SEQ ID NO: 454); or

GAGAAAGACAAUAUAGUUCU (SEQ ID NO: 453).

In an embodiment, when the CF target mutant position is R553, e.g., R553X, and two gRNAs are used to position two breaks, e.g., two single stranded breaks, in the target nucleic acid sequence, each guide RNA is independently selected from one of Tables 25A-25D, 26A- 26E, or 27A-27D.

In an embodiment, a mutation in the CFTR gene, e.g., at 371 7+1 21 91 C>T, also known as 3849+10kbC>T is targeted, e.g., for correction. In an embodiment, the targeting domain of a gRNA molecule comprises a sequence that is the same as, or differs by no more than 1, 2, 3, 4, or 5 nucleotides from, a targeting domain sequence from any one of Tables 34A-34D, 35A-35D, or 36A-36D. In some embodiments, the targeting domain is independently selected from those

15

5535.1 in Tables 34A-34D, 35A-35D, or 36A-36D. For example, in certain embodiments, the targeting domain is selected from:

GAGUAAGACACCCUGAA (SEQ ID NO: 3344);

GAUUUCUGGAGACCACA (SEQ ID NO: 3345);

GGUUUUAGCUAUUACUC (SEQ ID NO: 3346);

GUAGUUGAAUCAUUCAG (SEQ ID NO: 3347);

GAACUCAGUUUUUAGGU (SEQ ID NO: 3348);

GAAAGGAAAUGUUCUAUUCA (SEQ ID NO: 3349);

GUUUUUAGGUUGGGAAAGAC (SEQ ID NO: 3350);

GCACAUAAUAAUUAGUUUCC (SEQ ID NO: 3351);

GAGAACUCAGUUUUUAGGUU (SEQ ID NO: 3352); or

GAAAACACUGACUUAGAUUU (SEQ ID NO: 3353).

In an embodiment, when the CF target mutant position is 371 7+121 91 C>T and two gRNAs are used to position two breaks, e.g., two single stranded breaks, in the target nucleic acid sequence, each guide RNA is independently selected from one of Tables 34A-34D, 35A- 35D, or 36A-36D.

In an embodiment, a mutation in the CFTR gene, e.g., at 2657+5G>A, also known as 2789+5G>A is targeted, e.g., for correction. In an embodiment, the targeting domain of a gRNA molecule comprises a sequence that is the same as, or differs by no more than 1, 2, 3, 4, or 5 nucleotides from, a targeting domain sequence from any one of Tables 4A-4D, 5A-5E, or 6A-6C. In some embodiments, the targeting domain is independently selected from those in Tables 4A-4D, 5A-5E, or 6A-6C. For example, in certain embodiments, the targeting domain is selected from:

GAAGCAGCCACCUGGAA (SEQ ID NO: 937);

GGAAUAUUCACUUUCCA (SEQ ID NO: 938);

GAAUUUAGAUGUGGGCA (SEQ ID NO: 939);

GUGUCUUGUUCCAUUCC (SEQ ID NO: 940);

GUGGGCAUGGGAGGAAU (SEQ ID NO: 941);

GUUGUGCUGUGGCUCCU (SEQ ID NO: 942);

GAUGUGAAUUUAGAUGU (SEQ ID NO: 943);

GACCCAGGAACACAAAGCAA (SEQ ID NO: 944);

16

5535.1 GUGUCACCUCACCCAACUAA (SEQ ID NO: 945);

GUGUCUUGUUCCAUUCCAGG (SEQ ID NO: 946);

GAUGUGGGCAUGGGAGGAAU (SEQ ID NO: 947);

GUGAAUUUAGAUGUGGGCAU (SEQ ID NO: 948).

In an embodiment, when the CF target mutant position is 2657+5G>A and two gRNAs are used to position two breaks, e.g., two single stranded breaks, in the target nucleic acid sequence, each guide RNA is independently selected from one of Tables 4A-4D, 5A-5E, or 6A- 6C.

In an embodiment, a mutation in the CFTR gene, e.g., at 3140-26A>G, also known as 3272-26A>G, is targeted, e.g., for correction. In an embodiment, the targeting domain of a gRNA molecule comprises a sequence that is the same as, or differs by no more than 1, 2, 3, 4, or 5 nucleotides from, a targeting domain sequence from any one of Tables 7A-7D, 8A-8E, or 9A-9B. In some embodiments, the targeting domain is independently selected from those in Tables 7A-7D, 8A-8E, or 9A-9B. For example, in certain embodiments, the targeting domain is selected from:

GUAAGGCUGCCGUCCGA (SEQ ID NO: 1282);

GGAAAUAUUUCACAGGC (SEQ ID NO: 1283);

GUAAAUUCAGAGCUUUG (SEQ ID NO: 1284);

GGACACUUCGUGCCUUCGGA (SEQ ID NO: 1285);

GGAACCAGCGCAGUGUUGAC (SEQ ID NO: 1286);

GUAACAAGAUGAGUGAAAAU (SEQ ID NO: 1287).

In an embodiment, when the CF target mutant position is 3140-26 A>G and two gRNAs are used to position two breaks, e.g., two single stranded breaks, in the target nucleic acid sequence, each guide RNA is independently selected from one of Tables 7A-7D, 8A-8E, or 9A- 9B.

In another embodiment, a CF target knockout position, e.g., a position in the coding region, e.g., the early coding region, of the SCNN1A gene is targeted, e.g., for knockout. In an embodiment, the targeting domain comprises a sequence that is the same as, or differs by no more than 1, 2, 3, 4, or 5 nucleotides from, a targeting domain sequence from any one of Tables 3A-3D, 43A-43E, 44A-44G, or 45A-45E. In an embodiment, the targeting domain is

17

5535.1 independently selected from those in Tables 3A-3D, 43A-43E, 44A-44G, or 45A-45E. In another embodiment, the targeting domain is independently selected from:

GCCCAUACCAGGUCUCAUGG (SEQ ID NO: 497);

CCAUACCAGGUCUCAUGGAG (SEQ ID NO: 498);

GCCCUCCACAGUCCACUCCA (SEQ ID NO: 499);

CCCCUCCAUGAGACCUGGUA (SEQ ID NO: 500);

AUACCAGGUCUCAUGGA (SEQ ID NO: 501); or

CUCCAUGAGACCUGGUA (SEQ ID NO: 502).

In an embodiment, when the CF target knockout position is the SCNNIA coding region, e.g., early coding region, and more than one gRNA is used to position breaks, e.g., two single stranded breaks or two double stranded breaks, or a combination of single strand and double strand breaks, e.g., to create one or more indels, in the target nucleic acid sequence, each guide RNA is independently selected from one of Tables 3A-3D, 43A-43E, 44A-44G, or 45A-45E.

In an embodiment, the targeting domain of the gRNA molecule is configured to target an enzymatically inactive Cas9 (eiCas9) molecule or an eiCas9 fusion protein (e.g., an eiCas9 fused to a transcription repressor domain), sufficiently close to a SCNNIA transcription start site (TSS) to reduce (e.g., block) transcription, e.g., transcription initiation or elongation, binding of one or more transcription enhancers or activators, and/or RNA polymerase. In an embodiment, the targeting domain is configured to target between 1000 bp upstream and 1000 bp downstream (e.g., between 500 bp upstream and 1000 bp downstream, between 1000 bp upstream and 500 bp downstream, between 500 bp upstream and 500 bp downstream, within 500 bp upstream, or within 500 bp downstream) of the TSS of the SCNNIA gene. One or more gRNAs may be used to target an eiCas9 to the promoter region of the SCNNIA gene.

In an embodiment, when the SCNNIA promoter region is targeted, e.g., for knockdown, the targeting domain can comprise a sequence that is the same as, or differs by no more than 1, 2, 3, 4, or 5 nucleotides from, a targeting domain sequence from any one of Tables 46A-46E, 47A- 47G, or 48A-48E. In an embodiment, the targeting domain is independently selected from those in Tables 46A-46E, 47A-47G, or 48A-48E.

In an embodiment, the targeting domain is independently selected from those in Table 46A. In an embodiment, the targeting domain is independently selected from those in Table

18

5535.1 47A. In an embodiment, the targeting domain is independently selected from those in Table 48A.

In an embodiment, when the CF target knockdown position is the SCNN1A promoter region and more than one gRNA is used to position an eiCas9 molecule or an eiCas9-fusion protein (e.g., an eiCas9-transcription repressor domain fusion protein), in the target nucleic acid sequence, the targeting domain for each guide RNA is independently selected from one of

Tables 46A-46E, 47A-47G, or 48A-48E.

In an embodiment, the gRNA, e.g., a gRNA comprising a targeting domain, which is complementary with the CFTR gene or SCNN1A gene, is a modular gRNA. In other

embodiments, the gRNA is a unimolecular or chimeric gRNA.

In an embodiment, the targeting domain which is complementary with a target domain from the CF target position in the CFTR gene or SCNN1A gene is 16 nucleotides or more in length. In an embodiment, the targeting domain is 16 nucleotides in length. In an embodiment, the targeting domain is 17 nucleotides in length. In another embodiment, the targeting domain is 18 nucleotides in length. In still another embodiment, the targeting domain is 19 nucleotides in length. In still another embodiment, the targeting domain is 20 nucleotides in length. In still another embodiment, the targeting domain is 21 nucleotides in length. In still another embodiment, the targeting domain is 22 nucleotides in length. In still another embodiment, the targeting domain is 23 nucleotides in length. In still another embodiment, the targeting domain is 24 nucleotides in length. In still another embodiment, the targeting domain is 25 nucleotides in length. In still another embodiment, the targeting domain is 26 nucleotides in length.

In an embodiment, the targeting domain comprises 16 nucleotides.

In an embodiment, the targeting domain comprises 17 nucleotides.

In an embodiment, the targeting domain comprises 18 nucleotides.

In an embodiment, the targeting domain comprises 19 nucleotides.

In an embodiment, the targeting domain comprises 20 nucleotides.

In an embodiment, the targeting domain comprises 21 nucleotides.

In an embodiment, the targeting domain comprises 22 nucleotides.

In an embodiment, the targeting domain comprises 23 nucleotides.

In an embodiment, the targeting domain comprises 24 nucleotides.

In an embodiment, the targeting domain comprises 25 nucleotides.

19

5535.1 In an embodiment, the targeting domain comprises 26 nucleotides.

A gRNA as described herein may comprise from 5' to 3': a targeting domain

(comprising a "core domain", and optionally a "secondary domain"); a first complementarity domain; a linking domain; a second complementarity domain; a proximal domain; and a tail domain. In some embodiments, the proximal domain and tail domain are taken together as a single domain.

In an embodiment, a gRNA comprises a linking domain of no more than 25 nucleotides in length; a proximal and tail domain, that taken together, are at least 20 nucleotides in length; and a targeting domain equal to or greather than 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or 26nucleotides in length.

In another embodiment, a gRNA comprises a linking domain of no more than 25 nucleotides in length; a proximal and tail domain, that taken together, are at least 30 nucleotides in length; and a targeting domain equal to or greather than 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or 26nucleotides in length.

In another embodiment, a gRNA comprises a linking domain of no more than 25 nucleotides in length; a proximal and tail domain, that taken together, are at least 35 nucleotides in length; and a targeting domain equal to or greather than 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or 26nucleotides in length.

In another embodiment, a gRNA comprises a linking domain of no more than 25 nucleotides in length; a proximal and tail domain, that taken together, are at least 40 nucleotides in length; and a targeting domain equal to or greather than 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or 26nucleotides in length.

A cleavage event, e.g., a double strand or single strand break, is generated by a Cas9 molecule. The Cas9 molecule may be an enzymatically active Cas9 (eaCas9) molecule, e.g., an eaCas9 molecule that forms a double strand break in a target nucleic acid or an eaCas9 molecule forms a single strand break in a target nucleic acid (e.g., a nickase molecule).

In an embodiment, the eaCas9 molecule catalyzes a double strand break.

In some embodiments, the eaCas9 molecule comprises HNH-like domain cleavage activity but has no, or no significant, N-terminal RuvC-like domain cleavage activity. In this case, the eaCas9 molecule is an HNH-like domain nickase, e.g., the eaCas9 molecule comprises a mutation at D10, e.g., D10A. In other embodiments, the eaCas9 molecule comprises N-

20

5535.1 terminal RuvC-like domain cleavage activity but has no, or no significant, HNH-like domain cleavage activity. In an embodiment, the eaCas9 molecule is an N-terminal RuvC-like domain nickase, e.g., the eaCas9 molecule comprises a mutation at H840, e.g., H840A. In an

embodiment, the eaCas9 molecule is an N-terminal RuvC-like domain nickase, e.g., the eaCas9 molecule comprises a mutation at N863, e.g., an N863A mutation.

In an embodiment, a single strand break is formed in the strand of the target nucleic acid to which the targeting domain of said gRNA is complementary. In another embodiment, a single strand break is formed in the strand of the target nucleic acid other than the strand to which the targeting domain of said gRNA is complementary.

In another aspect, disclosed herein is a nucleic acid, e.g., an isolated or non-naturally occurring nucleic acid, e.g., DNA, that comprises (a) a sequence that encodes a gRNA molecule comprising a targeting domain that is complementary with a target domain, e.g., with a CF target position, in the CFTR gene or SCNNIA gene as disclosed herein.

In an embodiment, the nucleic acid encodes a gRNA molecule, e.g., a first gRNA molecule, comprising a targeting domain configured to provide a cleavage event, e.g., a double strand break or a single strand break, sufficiently close to a CF target position in the CFTR gene or SCNNIA gene to allow alteration, e.g., alteration associated with, respectively, HDR or NHEJ, of a CF target position in the CFTR gene or SCNNIA gene.

In an embodiment, the nucleic acid encodes a gRNA molecule, e.g., a first gRNA molecule, comprising a targeting domain configured to target an enzymatically inactive Cas9

(eiCas9) molecule or an eiCas9 fustion protein (e.g., an eiCas9 fused to a transcription repressor domain), sufficiently close to a CF knockdown target position to reduce, decrease or repress expression of the SCNNIA gene.

In an embodiment, the nucleic acid encodes a gRNA molecule, e.g., the first gRNA molecule, comprising a targeting domain comprising a sequence that is the same as, or differs by no more than 1, 2, 3, 4, or 5 nucleotides from, a targeting domain sequence as described herein, e.g., from any one of Tables 1A-1E, 2A-2E, 3A-3D, 4A-4D, 5A-5E, 6A-6C, 7A-7D, 8A-8E, 9A-9B, lOA-lOC, 11A-11E, 12A-12C, 13A-13D, 14A-14E, 15A-15C, or 16A-16D, 17A-17E, 18A-18C, 19A-19D, 20A-20E, 21A-21B, 22A-22D, 23A-23E, 24A-24D, 25A-25D, 26A-26E, 27A-27D, 28A-28D, 29A-29E, 30A-30B, 31A-31D, 32A-32D, 33A-33B, 34A-34D, 35A-35D, 36A-36D, 37A-37D, 38A-38E, 39A-39D, 40A-40D, 41A-41E, 42A-42D, 43A-43E, 44A-44G,

21

5535.1 45A-45E, 46A-46E, 47A-47G, or 48A-48E. In an embodiment, the nucleic acid encodes a gRNA molecule comprising a targeting domain as described herein, e.g., that is selected from those in Tables 1A-1E, 2A-2E, 3A-3D, 4A-4D, 5A-5E, 6A-6C, 7A-7D, 8A-8E, 9A-9B, 10A- 10C, 11A-11E, 12A-12C, 13A-13D, 14A-14E, 15A-15C, or 16A-16D, 17A-17E, 18A-18C, 19A-19D, 20A-20E, 21A-21B, 22A-22D, 23A-23E, 24A-24D, 25A-25D, 26A-26E, 27A-27D, 28A-28D, 29A-29E, 30A-30B, 31A-31D, 32A-32D, 33A-33B, 34A-34D, 35A-35D, 36A-36D, 37A-37D, 38A-38E, 39A-39D, 40A-40D, 41A-41E, 42A-42D, 43A-43E, 44A-44G, 45A-45E, 46A-46E, 47A-47G, or 48A-48E.

In an embodiment, the nucleic acid encodes a modular gRNA, e.g., one or more nucleic acids encode a modular gRNA. In another embodiment, the nucleic acid encodes a chimeric gRNA. The nucleic acid may encode a gRNA, e.g., the first gRNA molecule, comprising a targeting domain comprising 16 nucleotides or more in length. In an embodiment, the nucleic acid encodes a gRNA, e.g., the first gRNA molecule, comprising a targeting domain that is 16 nucleotides in length. In another embodiment, the nucleic acid encodes a gRNA, e.g., the first gRNA molecule, comprising a targeting domain that is 17 nucleotides in length. In yet another embodiment, the nucleic acid encodes a gRNA, e.g., the first gRNA molecule, comprising a targeting domain that is 18 nucleotides in length. In still another embodiment, the nucleic acid encodes a gRNA, e.g., the first gRNA molecule, comprising a targeting domain that is 19 nucleotides in length. In still another embodiment, the nucleic acid encodes a gRNA, e.g., the first gRNA molecule, comprising a targeting domain that is 20 nucleotides in length. In still another embodiment, the nucleic acid encodes a gRNA, e.g., the first gRNA molecule, comprising a targeting domain that is 21 nucleotides in length. In still another embodiment, the nucleic acid encodes a gRNA, e.g., the first gRNA molecule, comprising a targeting domain that is 22 nucleotides in length. In still another embodiment, the nucleic acid encodes a gRNA, e.g., the first gRNA molecule, comprising a targeting domain that is 23 nucleotides in length. In still another embodiment, the nucleic acid encodes a gRNA, e.g., the first gRNA molecule, comprising a targeting domain that is 24 nucleotides in length. In still another embodiment, the nucleic acid encodes a gRNA, e.g., the first gRNA molecule, comprising a targeting domain that is 25 nucleotides in length. In still another embodiment, the nucleic acid encodes a gRNA, e.g., the first gRNA molecule, comprising a targeting domain that is 26 nucleotides in length.

In an embodiment, the targeting domain comprises 16 nucleotides.

22

5535.1 In an embodiment, the targeting domain comprises 17 nucleotides.

In an embodiment, the targeting domain comprises 18 nucleotides.

In an embodiment, the targeting domain comprises 19 nucleotides.

In an embodiment, the targeting domain comprises 20 nucleotides.

In an embodiment, the targeting domain comprises 21 nucleotides.

In an embodiment, the targeting domain comprises 22 nucleotides.

In an embodiment, the targeting domain comprises 23 nucleotides.

In an embodiment, the targeting domain comprises 24 nucleotides.

In an embodiment, the targeting domain comprises 25 nucleotides.

In an embodiment, the targeting domain comprises 26 nucleotides.

In an embodiment, a nucleic acid encodes a gRNA comprising from

domain (comprising a "core domain", and optionally a "secondary domain"); a first

complementarity domain; a linking domain; a second complementarity domain; a proximal domain; and a tail domain. In some embodiments, the proximal domain and tail domain are taken together as a single domain.

In an embodiment, a nucleic acid encodes a gRNA e.g., the first gRNA molecule, comprising a linking domain of no more than 25 nucleotides in length; a proximal and tail domain, that taken together, are at least 20 nucleotides in length; and a targeting domain equal to or greater than 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or 26 nucleotides in length.

In an embodiment, a nucleic acid encodes a gRNA e.g., the first gRNA molecule, comprising a linking domain of no more than 25 nucleotides in length; a proximal and tail domain, that taken together, are at least 30 nucleotides in length; and a targeting domain equal to or greater than 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or 26 nucleotides in length.

In an embodiment, a nucleic acid encodes a gRNA e.g., the first gRNA molecule, comprising a linking domain of no more than 25 nucleotides in length; a proximal and tail domain, that taken together, are at least 35 nucleotides in length; and a targeting domain equal to or greater than 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or 26 nucleotides in length.

In an embodiment, a nucleic acid encodes a gRNA comprising e.g., the first gRNA molecule, a linking domain of no more than 25 nucleotides in length; a proximal and tail domain, that taken together, are at least 40 nucleotides in length; and a targeting domain equal to or greater than 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or 26 nucleotides in length.

23

5535.1 In an embodiment, a nucleic acid comprises (a) a sequence that encodes a gRNA molecule, e.g., the first gRNA molecule, comprising a targeting domain that is complementary with a target domain in the CFTR gene or SCNN1A gene as disclosed herein, and further comprising (b) a sequence that encodes a Cas9 molecule.

The Cas9 molecule may be a nickase molecule, an enzymatically activating Cas9

(eaCas9) molecule, e.g., an eaCas9 molecule that forms a double strand break in a target nucleic acid and/or an eaCas9 molecule forms a single strand break in a target nucleic acid. In an embodiment, a single strand break is formed in the strand of the target nucleic acid to which the targeting domain of said gRNA is complementary. In another embodiment, a single strand break is formed in the strand of the target nucleic acid other than the strand to which to which the targeting domain of said gRNA is complementary.

In an embodiment, the eaCas9 molecule catalyzes a double strand break.

In an embodiment, the eaCas9 molecule comprises HNH-like domain cleavage activity but has no, or no significant, N-terminal RuvC-like domain cleavage activity. In another embodiment, the said eaCas9 molecule is an HNH-like domain nickase, e.g., the eaCas9 molecule comprises a mutation at D10, e.g., D10A. In another embodiment, the eaCas9 molecule comprises N-terminal RuvC-like domain cleavage activity but has no, or no significant, HNH-like domain cleavage activity. In another embodiment, the eaCas9 molecule is an N- terminal RuvC-like domain nickase, e.g., the eaCas9 molecule comprises a mutation at H840, e.g., H840A. In another embodiment, the eaCas9 molecule is an N-terminal RuvC-like domain nickase, e.g., the eaCas9 molecule comprises a mutation at N863, e.g., an N863A mutation.

A nucleic acid disclosed herein may comprise (a) a sequence that encodes a gRNA molecule comprising a targeting domain that is complementary with a target domain in the CFTR and/or SCNN1A gene as disclosed herein; (b) a sequence that encodes a Cas9 molecule.

In an embodiment, the Cas9 molecule is an enzymatically active Cas9 (eaCas9) molecule.

In an embodiment, the Cas9 molecule is an enzymatically inactive Cas9 (eiCas9) molecule or a modified eiCas9 molecule, e.g., the eiCas9 molecule is fused to Kriippel-associated box (KRAB) to generate an eiCas9-KRAB fusion protein molecule.

A nucleic acid disclosed herein may comprise (a) a sequence that encodes a gRNA molecule comprising a targeting domain that is complementary with a target domain in the CFTR gene or SCNN1A gene as disclosed herein; (b) a sequence that encodes a Cas9 molecule; and

24

5535.1 further may comprise (c)(i) a sequence that encodes a second gRNA molecule described herein having a targeting domain that is complementary to a second target domain of the CFTR gene or SCNNIA gene, and optionally, (c)(ii) a sequence that encodes a third gRNA molecule described herein having a targeting domain that is complementary to a third target domain of the CFTR gene or SCNNIA gene; and optionally, (c)(iii) a sequence that encodes a fourth gRNA molecule described herein having a targeting domain that is complementary to a fourth target domain of the CFTR gene or SCNNIA gene.

In an embodiment, a nucleic acid encodes a second gRNA molecule comprising a targeting domain configured to provide a cleavage event, e.g., a double strand break or a single strand break, sufficiently close to a CF target position in the CFTR gene or SCNNIA gene, to allow alteration, e.g., alteration associated with, respectively, HDR or NHEJ, of a CF target position in the CFTR gene or SCNNIA gene, either alone or in combination with the break positioned by said first gRNA molecule.

In an embodiment, a nucleic acid encodes a second gRNA molecule comprising a targeting domain configured to target an enzymatically inactive Cas9 (eiCas9) molecule or an eiCas9 fustion protein (e.g., an eiCas9 fused to a transcription repressor domain), sufficiently close to a CF knockdown target position to reduce, decrease or repress expression of the SCNNIA gene.

In an embodiment, a nucleic acid encodes a third gRNA molecule comprising a targeting domain configured to provide a cleavage event, e.g., a double strand break or a single strand break, sufficiently close to a CF target position in the CFTR gene or SCNNIA gene to allow alteration, e.g., alteration associated with, respectively, HDR or NHEJ, of a CF target position in the CFTR gene or SCNNIA gene, either alone or in combination with the break positioned by the first and/or second gRNA molecule.

In an embodiment, a nucleic acid encodes a third gRNA molecule comprising a targeting domain configured to target an enzymatically inactive Cas9 (eiCas9) molecule or an eiCas9 fustion protein (e.g., an eiCas9 fused to a transcription repressor domain), sufficiently close to a CF knockdown target position to reduce, decrease or repress expression of the SCNNIA gene.

In an embodiment, a nucleic acid encodes a fourth gRNA molecule comprising a targeting domain configured to provide a cleavage event, e.g., a double strand break or a single strand break, sufficiently close to a CF target position in the CFTR gene or SCNNIA gene to

25

5535.1 allow alteration, e.g., alteration associated with, respectively, HDR or NHEJ, of a CF target position in the CFTR gene or SCNN1A gene, either alone or in combination with the break positioned by the first gRNA molecule, the second gRNA molecule and/or the third gRNA molecule.

In an embodiment, the nucleic acid encodes a second gRNA molecule. The second gRNA is selected to target the same CF target position as the first gRNA molecule. Optionally, the nucleic acid may encode a third gRNA, and further optionally, the nucleic acid may encode a fourth gRNA molecule. The third gRNA molecule and the fourth gRNA molecule are selected to target the same CF target position as the first and second gRNA molecules.

In an embodiment, the nucleic acid encodes a second gRNA molecule comprising a targeting domain comprising a sequence that is the same as, or differs by no more than 1, 2, 3, 4, or 5 nucleotides from, a targeting domain sequence from one of Tables 1A-1E, 2A-2E, 3A-3D, 4A-4D, 5A-5E, 6A-6C, 7A-7D, 8A-8E, 9A-9B, lOA-lOC, 11A-11E, 12A-12C, 13A-13D, 14A- 14E, 15A-15C, or 16A-16D, 17A-17E, 18A-18C, 19A-19D, 20A-20E, 21A-21B, 22A-22D, 23A-23E, 24A-24D, 25A-25D, 26A-26E, 27A-27D, 28A-28D, 29A-29E, 30A-30B, 31A-31D, 32A-32D, 33A-33B, 34A-34D, 35A-35D, 36A-36D, 37A-37D, 38A-38E, 39A-39D, 40A-40D, 41A-41E, 42A-42D, 43A-43E, 44A-44G, 45A-45E, 46A-46E, 47A-47G, or 48A-48E. In an embodiment, the nucleic acid encodes a second gRNA molecule comprising a targeting domain selected from those in Tables 1A-1E, 2A-2E, 3A-3D, 4A-4D, 5A-5E, 6A-6C, 7A-7D, 8A-8E, 9A-9B, lOA-lOC, 11A-11E, 12A-12C, 13A-13D, 14A-14E, 15A-15C, or 16A-16D, 17A-17E, 18A-18C, 19A-19D, 20A-20E, 21A-21B, 22A-22D, 23A-23E, 24A-24D, 25A-25D, 26A-26E, 27A-27D, 28A-28D, 29A-29E, 30A-30B, 31A-31D, 32A-32D, 33A-33B, 34A-34D, 35A-35D, 36A-36D, 37A-37D, 38A-38E, 39A-39D, 40A-40D, 41A-41E, 42A-42D, 43A-43E, 44A-44G, 45A-45E, 46A-46E, 47A-47G, or 48A-48E. In an embodiment, when a third or fourth gRNA molecule are present, the third and fourth gRNA molecules may independently comprise a targeting domain comprising a sequence that is the same as, or differs by no more than 1, 2, 3, 4, or 5 nucleotides from, a targeting domain sequence from one of Tables 1A-1E, 2A-2E, 3A-3D, 4A-4D, 5A-5E, 6A-6C, 7A-7D, 8A-8E, 9A-9B, lOA-lOC, 11A-11E, 12A-12C, 13A-13D, 14A- 14E, 15A-15C, or 16A-16D, 17A-17E, 18A-18C, 19A-19D, 20A-20E, 21A-21B, 22A-22D, 23A-23E, 24A-24D, 25A-25D, 26A-26E, 27A-27D, 28A-28D, 29A-29E, 30A-30B, 31A-31D, 32A-32D, 33A-33B, 34A-34D, 35A-35D, 36A-36D, 37A-37D, 38A-38E, 39A-39D, 40A-40D,

26

5535.1 41A-41E, 42A-42D, 43A-43E, 44A-44G, 45A-45E, 46A-46E, 47A-47G, or 48A-48E. In a further embodiment, when a third or fourth gRNA molecule are present, the third and fourth gRNA molecules may independently comprise a targeting domain selected from those in Tables 1A-1E, 2A-2E, 3A-3D, 4A-4D, 5A-5E, 6A-6C, 7A-7D, 8A-8E, 9A-9B, lOA-lOC, 11A-11E, 12A-12C, 13A-13D, 14A-14E, 15A-15C, or 16A-16D, 17A-17E, 18A-18C, 19A-19D, 20A- 20E, 21A-21B, 22A-22D, 23A-23E, 24A-24D, 25A-25D, 26A-26E, 27A-27D, 28A-28D, 29A- 29E, 30A-30B, 31A-31D, 32A-32D, 33A-33B, 34A-34D, 35A-35D, 36A-36D, 37A-37D, 38A- 38E, 39A-39D, 40A-40D, 41A-41E, 42A-42D, 43A-43E, 44A-44G, 45A-45E, 46A-46E, 47A- 47G, or 48A-48E.

In an embodiment, the nucleic acid encodes a second gRNA which is a modular gRNA, e.g., wherein one or more nucleic acid molecules encode a modular gRNA. In another embodiment, the nucleic acid encoding a second gRNA is a chimeric gRNA. In another embodiment, when a nucleic acid encodes a third or fourth gRNA, the third and fourth gRNA may be a modular gRNA or a chimeric gRNA. When multiple gRNAs are used, any

combination of modular or chimeric gRNAs may be used.

A nucleic acid may encode a second, a third, and/or a fourth gRNA, each independently, comprising a targeting domain comprising 16 nucleotides or more in length. In an embodiment, the nucleic acid encodes a second gRNA comprising a targeting domain that is 16 nucleotides in length. In an embodiment, the nucleic acid encodes a second gRNA comprising a targeting domain that is 17 nucleotides in length. In another embodiment, the nucleic acid encodes a second gRNA comprising a targeting domain that is 18 nucleotides in length. In still another embodiment, the nucleic acid encodes a second gRNA comprising a targeting domain that is 19 nucleotides in length. In still another embodiment, the nucleic acid encodes a second gRNA comprising a targeting domain that is 20 nucleotides in length. In still another embodiment, the nucleic acid encodes a second gRNA comprising a targeting domain that is 21 nucleotides in length. In still another embodiment, the nucleic acid encodes a second gRNA comprising a targeting domain that is 22 nucleotides in length. In still another embodiment, the nucleic acid encodes a second gRNA comprising a targeting domain that is 23 nucleotides in length. In still another embodiment, the nucleic acid encodes a second gRNA comprising a targeting domain that is 24 nucleotides in length. In still another embodiment, the nucleic acid encodes a second gRNA comprising a targeting domain that is 25 nucleotides in length. In still another

27

5535.1 embodiment, the nucleic acid encodes a second gRNA comprising a targeting domain that is 26 nucleotides in length.

In an embodiment, the targeting domain comprises 16 nucleotides.

In an embodiment, the targeting domain comprises 17 nucleotides.

In an embodiment, the targeting domain comprises 18 nucleotides.

In an embodiment, the targeting domain comprises 19 nucleotides.

In an embodiment, the targeting domain comprises 20 nucleotides.

In an embodiment, the targeting domain comprises 21 nucleotides.

In an embodiment, the targeting domain comprises 22 nucleotides.

In an embodiment, the targeting domain comprises 23 nucleotides.

In an embodiment, the targeting domain comprises 24 nucleotides.

In an embodiment, the targeting domain comprises 25 nucleotides.

In an embodiment, the targeting domain comprises 26 nucleotides.

In an embodiment, a nucleic acid encodes a second, a third, and/or

independently, comprising from 5' to 3': a targeting domain (comprising a "core domain", and optionally a "secondary domain"); a first complementarity domain; a linking domain; a second complementarity domain; a proximal domain; and a tail domain. In some embodiments, the proximal domain and tail domain are taken together as a single domain.

In an embodiment, a nucleic acid encodes a second, a third, and/or a fourth gRNA comprising a linking domain of no more than 25 nucleotides in length; a proximal and tail domain, that taken together, are at least 20 nucleotides in length; and a targeting domain equal to or greater thanl6, 17, 18, 19, 20, 21, 22, 23, 24, 25 or 26nucleotides in length.

In an embodiment, a nucleic acid encodes a second, a third, and/or a fourth gRNA comprising a linking domain of no more than 25 nucleotides in length; a proximal and tail domain, that taken together, are at least 30 nucleotides in length; and a targeting domain equal to or greater thanl6, 17, 18, 19, 20, 21, 22, 23, 24, 25 or 26nucleotides in length.

In an embodiment, a nucleic acid encodes a second, a third, and/or a fourth gRNA comprising a linking domain of no more than 25 nucleotides in length; a proximal and tail domain, that taken together, are at least 35 nucleotides in length; and a targeting domain equal to or greater thanl6, 17, 18, 19, 20, 21, 22, 23, 24, 25 or 26nucleotides in length.

28

5535.1 In an embodiment, a nucleic acid encodes a second, a third, and/or a fourth gRNA comprising a linking domain of no more than 25 nucleotides in length; a proximal and tail domain, that taken together, are at least 40 nucleotides in length; and a targeting domain equal to or greater thanl6, 17, 18, 19, 20, 21, 22, 23, 24, 25 or 26nucleotides in length.

In an embodiment, when the CFTR gene is corrected by HDR, the nucleic acid encodes

(a) a sequence that encodes a gRNA molecule comprising a targeting domain that is

complementary with a target domain in the CFTR gene as disclosed herein; (b) a sequence that encodes a Cas9 molecule; optionally, (c)(i) a sequence that encodes a second gRNA molecule described herein having a targeting domain that is complementary to a second target domain of the CFTR gene, and further optionally, (c)(ii) a sequence that encodes a third gRNA molecule described herein having a targeting domain that is complementary to a third target domain of the CFTR gene; and still further optionally, (c)(iii) a sequence that encodes a fourth gRNA molecule described herein having a targeting domain that is complementary to a fourth target domain of the CFTR gene; and further may comprise (d) a template nucleic acid, e.g., a template nucleic acid described herein.

In an embodiment, the template nucleic acid is a single stranded nucleic acid. In another embodiment, the template nucleic acid is a double stranded nucleic acid. In an embodiment, the template nucleic acid comprises a nucleotide sequence, e.g., of one or more nucleotides, that will be added to or will template a change in the target nucleic acid. In another embodiment, the template nucleic acid comprises a nucleotide sequence that may be used to modify the target position. In another embodiment, the template nucleic acid comprises a nucleotide sequence, e.g., of one or more nucleotides, that corresponds to wild type sequence of the target nucleic acid, e.g., of the target position.

The template nucleic acid may comprise a replacement sequence, e.g., a replacement sequence from the Table 49. In some embodiments, the template nucleic acid comprises a 5' homology arm, e.g., a 5' homology arm from Table 49. In other embodiments, the template nucleic acid comprises a 3' homology arm, e.g., a 3' homology arm from Table 49.

In an embodiment, a nucleic acid encodes (a) a sequence that encodes a gRNA molecule comprising a targeting domain that is complementary with a target domain in the CFTR gene or SCNNIA gene as disclosed herein, and (b) a sequence that encodes a Cas9 molecule, e.g., a Cas9 molecule described herein. In an embodiment, (a) and (b) are present on the same nucleic acid

29

5535.1 molecule, e.g., the same vector, e.g., the same viral vector, e.g., the same adeno-associated virus (AAV) vector. In an embodiment, the nucleic acid molecule is an AAV vector. Exemplary AAV vectors that may be used in any of the described compositions and methods include an AAV2 vector, a modified AAV2 vector, an AAV3 vector, a modified AAV3 vector, an AAV6 vector, a modified AAV6 vector, an AAV8 vector and an AAV9 vector.

In another embodiment, (a) is present on a first nucleic acid molecule, e.g. a first vector, e.g., a first viral vector, e.g., a first AAV vector; and (b) is present on a second nucleic acid molecule, e.g., a second vector, e.g., a second vector, e.g., a second AAV vector. The first and second nucleic acid molecules may be AAV vectors.

In another embodiment, the nucleic acid may further comprise (c) a sequence that encodes a second, third and/or fourth gRNA molecule as described herein. In another embodiment, the nucleic acid comprises (a), (b) and (c)(i). Each of (a) and (c)(i) may be present on the same nucleic acid molecule, e.g., the same vector, e.g., the same viral vector, e.g., the same adeno-associated virus (AAV) vector. In an embodiment, the nucleic acid molecule is an AAV vector.

In another embodiment, (a) and (c)(i) are on different vectors. For example, (a) may be present on a first nucleic acid molecule, e.g. a first vector, e.g., a first viral vector, e.g., a first AAV vector; and (c)(i) may be present on a second nucleic acid molecule, e.g., a second vector, e.g., a second vector, e.g., a second AAV vector. In an embodiment, the first and second nucleic acid molecules are AAV vectors.

In another embodiment, each of (a), (b), and (c)(i) are present on the same nucleic acid molecule, e.g., the same vector, e.g., the same viral vector, e.g., an AAV vector. In an embodiment, the nucleic acid molecule is an AAV vector. In an alternate embodiment, one of (a), (b), and (c)(i) is encoded on a first nucleic acid molecule, e.g., a first vector, e.g., a first viral vector, e.g., a first AAV vector; and a second and third of (a), (b), and (c)(i) is encoded on a second nucleic acid molecule, e.g., a second vector, e.g., a second vector, e.g., a second AAV vector. The first and second nucleic acid molecule may be AAV vectors.

In an embodiment, (a) is present on a first nucleic acid molecule, e.g., a first vector, e.g., a first viral vector, a first AAV vector; and (b) and (c)(i) are present on a second nucleic acid molecule, e.g., a second vector, e.g., a second vector, e.g., a second AAV vector. The first and second nucleic acid molecule may be AAV vectors.

30

5535.1 In another embodiment, (b) is present on a first nucleic acid molecule, e.g., a first vector, e.g., a first viral vector, e.g., a first AAV vector; and (a) and (c)(i) are present on a second nucleic acid molecule, e.g., a second vector, e.g., a second vector, e.g., a second AAV vector. The first and second nucleic acid molecule may be AAV vectors.

In another embodiment, (c)(i) is present on a first nucleic acid molecule, e.g., a first vector, e.g., a first viral vector, e.g., a first AAV vector; and (b) and (a) are present on a second nucleic acid molecule, e.g., a second vector, e.g., a second vector, e.g., a second AAV vector. The first and second nucleic acid molecule may be AAV vectors.

In another embodiment, each of (a), (b) and (c)(i) are present on different nucleic acid molecules, e.g., different vectors, e.g., different viral vectors, e.g., different AAV vector. For example, (a) may be on a first nucleic acid molecule, (b) on a second nucleic acid molecule, and (c)(i) on a third nucleic acid molecule. The first, second and third nucleic acid molecule may be AAV vectors.

In another embodiment, when a third and/or fourth gRNA molecule are present, each of (a), (b), (c)(i), (c)(ii) and (c)(iii) may be present on the same nucleic acid molecule, e.g., the same vector, e.g., the same viral vector, e.g., an AAV vector. In an embodiment, the nucleic acid molecule is an AAV vector. In an alternate embodiment, each of (a), (b), (c)(i), (c)(ii) and

(c) (iii) may be present on the different nucleic acid molecules, e.g., different vectors, e.g., the different viral vectors, e.g., different AAV vectors. In a further embodiment, each of (a), (b), (c)(i), (c)(ii) and (c)(iii) may be present on more than one nucleic acid molecule, but fewer than five nucleic acid molecules, e.g., AAV vectors.

In another embodiment, when (d) a template nucleic acid is present, each of (a), (b), and

(d) may be present on the same nucleic acid molecule, e.g., the same vector, e.g., the same viral vector, e.g., an AAV vector. In an embodiment, the nucleic acid molecule is an AAV vector. In an alternate embodiment, each of (a), (b), and (d) may be present on the different nucleic acid molecules, e.g., different vectors, e.g., the different viral vectors, e.g., different AAV vectors. In a further embodiment, each of (a), (b), and (d) may be present on more than one nucleic acid molecule, but fewer than three nucleic acid molecules, e.g., AAV vectors.

In another embodiment, when (d) a template nucleic acid is present, each of (a), (b), (c)(i) and (d) may be present on the same nucleic acid molecule, e.g., the same vector, e.g., the same viral vector, e.g., an AAV vector. In an embodiment, the nucleic acid molecule is an AAV

31

5535.1 vector. In an alternate embodiment, each of (a), (b), (c)(i) and (d) may be present on the different nucleic acid molecules, e.g., different vectors, e.g., the different viral vectors, e.g., different AAV vectors. In a further embodiment, each of (a), (b), (c)(i) and (d) may be present on more than one nucleic acid molecule, but fewer than four nucleic acid molecules, e.g., AAV vectors.

In another embodiment, when (d) a template nucleic acid is present, each of (a), (b),

(c) (i), (c)(ii) and (d) may be present on the same nucleic acid molecule, e.g., the same vector, e.g., the same viral vector, e.g., an AAV vector. In an embodiment, the nucleic acid molecule is an AAV vector. In an alternate embodiment, each of (a), (b), (c)(i), (c)(ii) and (d) may be present on the different nucleic acid molecules, e.g., different vectors, e.g., the different viral vectors, e.g., different AAV vectors. In a further embodiment, each of (a), (b), (c)(i), (c)(ii) and

(d) may be present on more than one nucleic acid molecule, but fewer than five nucleic acid molecules, e.g., AAV vectors.

In another embodiment, when (d) a template nucleic acid is present, each of (a), (b), (c)(i), (c)(ii), (c)(iii) and (d) may be present on the same nucleic acid molecule, e.g., the same vector, e.g., the same viral vector, e.g., an AAV vector. In an embodiment, the nucleic acid molecule is an AAV vector. In an alternate embodiment, each of (a), (b), (c)(i), (c)(ii), (c)(iii) and (d) may be present on the different nucleic acid molecules, e.g., different vectors, e.g., the different viral vectors, e.g., different AAV vectors. In a further embodiment, each of (a), (b), (c)(i), (c)(ii), (c)(iii) and (d) may be present on more than one nucleic acid molecule, but fewer than six nucleic acid molecules, e.g., AAV vectors.

The nucleic acids described herein may comprise a promoter operably linked to the sequence that encodes the gRNA molecule of (a), e.g., a promoter described herein. The nucleic acid may further comprise a second promoter operably linked to the sequence that encodes the second, third and/or fourth gRNA molecule of (c), e.g., a promoter described herein. The promoter and second promoter differ from one another. In some embodiments, the promoter and second promoter are the same.

The nucleic acids described herein may further comprise a promoter operably linked to the sequence that encodes the Cas9 molecule of (b), e.g., a promoter described herein.

In another aspect, disclosed herein is a composition comprising (a) a gRNA molecule comprising a targeting domain that is complementary with a target domain in the CFTR gene or

32

5535.1 SCNN1A gene, as described herein. The composition of (a) may further comprise (b) a Cas9 molecule, e.g., a Cas9 molecule as described herein. A composition of (a) and (b) may further comprise (c) a second, third and/or fourth gRNA molecule, e.g., a second, third and/or fourth gRNA molecule described herein. A composition of (a), (b) and (c) may further comprise (d) a template nucleic acid, e.g., a template nucleic acid described herein. In an embodiment, the composition is a pharmaceutical composition. The compositions described herein, e.g., pharmaceutical compositions described herein, can be used in the treatment or prevention of CF or CF-like disease in a subject, e.g., in accordance with a method disclosed herein.

In another aspect, disclosed herein is a method of altering a cell, e.g., altering the structure, e.g., altering the sequence, of a target nucleic acid of a cell, comprising contacting said cell with: (a) a gRNA that targets the CFTR gene or SCNN1A gene, e.g., a gRNA as described herein; (b) a Cas9 molecule, e.g., a Cas9 molecule as described herein; and optionally, (c) a second, third and/or fourth gRNA that targets CFTR gene or SCNN1A gene, e.g., a second, third and/or fourth gRNA as described herein; and optionally, (d) a template nucleic acid, e.g., a template nucleic acid as described herein.

In an embodiment, the method comprises contacting said cell with (a) and (b).

In an embodiment, the method comprises contacting said cell with (a), (b), and (c). In an embodiment, the method comprises contacting said cell with (a), (b), (c) and (d). The gRNA of (a) and optionally (c) may be selected from any of Tables 1A-1E, 2A-2E, 3A-3D, 4A-4D, 5A-5E, 6A-6C, 7A-7D, 8A-8E, 9A-9B, lOA-lOC, 11A-11E, 12A-12C, 13A- 13D, 14A-14E, 15A-15C, or 16A-16D, 17A-17E, 18A-18C, 19A-19D, 20A-20E, 21A-21B, 22A-22D, 23A-23E, 24A-24D, 25A-25D, 26A-26E, 27A-27D, 28A-28D, 29A-29E, 30A-30B, 31A-31D, 32A-32D, 33A-33B, 34A-34D, 35A-35D, 36A-36D, 37A-37D, 38A-38E, 39A-39D, 40A-40D, 41A-41E, 42A-42D, 43A-43E, 44A-44G, 45A-45E, 46A-46E, 47A-47G, or 48A- 48E, or a gRNA that differs by no more than 1, 2, 3, 4, or 5 nucleotides from, a targeting domain sequence from any of Tables 1A-1E, 2A-2E, 3A-3D, 4A-4D, 5A-5E, 6A-6C, 7A-7D, 8A-8E, 9A-9B, lOA-lOC, 11A-11E, 12A-12C, 13A-13D, 14A-14E, 15A-15C, or 16A-16D, 17A-17E, 18A-18C, 19A-19D, 20A-20E, 21A-21B, 22A-22D, 23A-23E, 24A-24D, 25A-25D, 26A-26E, 27A-27D, 28A-28D, 29A-29E, 30A-30B, 31A-31D, 32A-32D, 33A-33B, 34A-34D, 35A-35D, 36A-36D, 37A-37D, 38A-38E, 39A-39D, 40A-40D, 41A-41E, 42A-42D, 43A-43E, 44A-44G, 45A-45E, 46A-46E, 47A-47G, or 48A-48E.

33

5535.1 In an embodiment, the method comprises contacting a cell from a subject suffering from or likely to develop CF or CF-like disease. The cell may be from a subject having a mutation at a CF target position in the CFTR gene or a subject which would benefit from having a mutation at a CF target position in the SCNN1A gene.

In an embodiment, the cell being contacted in the disclosed method is an epithelial cell, e.g., a pulmonary epithelial cell, e.g., a bronchial epithelial cell or an alveolar epithelial cell. The contacting may be performed ex vivo and the contacted cell may be returned to the subject's body after the contacting step. In other embodiments, the contacting step may be performed in vivo.

In an embodiment, the method of altering a cell as described herein comprises acquiring knowledge of the sequence at a CF target position in said cell, prior to the contacting step.

Acquiring knowledge of the sequence at a CF target position in the cell may be by sequencing the CFTR gene or SCNN1A gene, or a portion of the CFTR gene or SCNN1A gene.

In an embodiment, the contacting step of the method comprises contacting the cell with a nucleic acid, e.g., a vector, e.g., an AAV vector, that expresses at least one of (a), (b), and (c). In an embodiment, the contacting step of the method comprises contacting the cell with a nucleic acid, e.g., a vector, e.g., an AAV vector, that expresses each of (a), (b), and (c). In another embodiment, the contacting step of the method comprises delivering to the cell a Cas9 molecule of (b) and a nucleic acid which encodes a gRNA of (a) and optionally, a second gRNA (c)(i) and further optionally, a third gRNA (c)(ii) and/or fourth gRNA (c)(iii)).

In an embodiment, the contacting step of the method comprises contacting the cell with a nucleic acid, e.g., a vector, e.g., an AAV vector, that expresses at least one of (a), (b), (c) and (d). In an embodiment, the contacting step of the method comprises contacting the cell with a nucleic acid, e.g., a vector, e.g., an AAV vector, that expresses each of (a), (b), and (c). In another embodiment, the contacting step of the method comprises delivering to the cell a Cas9 molecule of (b), a nucleic acid which encodes a gRNA of (a) and a template nucleic acid of (d), and optionally, a second gRNA (c)(i) and further optionally, a third gRNA (c)(ii) and/or fourth gRNA (c)(iii).

In an embodiment, contacting comprises contacting the cell with a nucleic acid, e.g., a vector, e.g., an AAV vector, e.g., an AAV2 vector, a modified AAV2 vector, an AAV3 vector, a modified AAV3 vector, an AAV6 vector, a modified AAV6 vector, an AAV8 vector or an AAV9 vector, as described herein.

In an embodiment, contacting comprises delivering to the cell a Cas9 molecule of (b), as a protein or an mRNA, and a nucleic acid which encodes a gRNA of (a) and optionally a second, third and/or fourth gRNA of (c).

In an embodiment, contacting comprises delivering to the cell a Cas9 molecule of (b), as a protein or an mRNA, said gRNA of (a), as an RNA, and optionally said second, third and/or fourth gRNA of (c), as an RNA.

In an embodiment, contacting comprises delivering to the cell a gRNA of (a) as an RNA, optionally the second, third and/or fourth gRNA of (c) as an RNA, and a nucleic acid that encodes the Cas9 molecule of (b).

In another aspect, disclosed herein is a method of treating or preventing a subject suffering from or likely to develop CF or CF-like disease, e.g., altering the structure, e.g., sequence, of a target nucleic acid of the subject, comprising contacting the subject (or a cell from the subject) with:

(a) a gRNA that targets the CFTR gene or SCNN1A gene, e.g., a gRNA disclosed herein;

(b) a Cas9 molecule, e.g., a Cas9 molecule disclosed herein; and

optionally, (c)(i) a second gRNA that targets the CFTR gene or SCNN1A gene, e.g., a second gRNA disclosed herein, and

further optionally, (c)(ii) a third gRNA, and still further optionally, (c)(iii) a fourth gRNA that target the CFTR gene or SCNN1A gene, e.g., a third and fourth gRNA disclosed herein.

The method of treating a subject may further comprise contacting the subject (or a cell from the subject) with (d) a template nucleic acid, e.g., a template nucleic acid disclosed herein. A template nucleic acid is used when the method of treating a subject uses HDR to alter the sequence of the target nucleic acid of the subject.

In some embodiments, contacting comprises contacting with (a) and (b).

In some embodiments, contacting comprises contacting with (a), (b), and (c)(i).

In some embodiments, contacting comprises contacting with (a), (b), (c)(i) and (c)(ii).

In some embodiments, contacting comprises contacting with (a), (b), (c)(i), (c)(ii) and (c)(iii).

In some embodiments, contacting comprises contacting with (a), (b), (c)(i) and (d). In some embodiments, contacting comprises contacting with (a), (b), (c)(i), (c)(ii) and

(d).

In some embodiments, contacting comprises contacting with (a), (b), (c)(i), (c)(ii), (c)(iii) and (d).

The gRNA of (a) or (c) (e.g., (c)(i), (c)(ii), or (c)(iii)) may be selected from any of Tables

1A-1E, 2A-2E, 3A-3D, 4A-4D, 5A-5E, 6A-6C, 7A-7D, 8A-8E, 9A-9B, lOA-lOC, 11A-11E, 12A-12C, 13A-13D, 14A-14E, 15A-15C, or 16A-16D, 17A-17E, 18A-18C, 19A-19D, 20A- 20E, 21A-21B, 22A-22D, 23A-23E, 24A-24D, 25A-25D, 26A-26E, 27A-27D, 28A-28D, 29A- 29E, 30A-30B, 31A-31D, 32A-32D, 33A-33B, 34A-34D, 35A-35D, 36A-36D, 37A-37D, 38A- 38E, 39A-39D, 40A-40D, 41A-41E, 42A-42D, 43A-43E, 44A-44G, 45A-45E, 46A-46E, 47A- 47G, or 48A-48E, or a gRNA that differs by no more than 1, 2, 3, 4, or 5 nucleotides from, a targeting domain sequence from any of Tables 1A-1E, 2A-2E, 3A-3D, 4A-4D, 5A-5E, 6A-6C, 7A-7D, 8A-8E, 9A-9B, lOA-lOC, 11A-11E, 12A-12C, 13A-13D, 14A-14E, 15A-15C, or 16A- 16D, 17A-17E, 18A-18C, 19A-19D, 20A-20E, 21A-21B, 22A-22D, 23A-23E, 24A-24D, 25A- 25D, 26A-26E, 27A-27D, 28A-28D, 29A-29E, 30A-30B, 31A-31D, 32A-32D, 33A-33B, 34A- 34D, 35A-35D, 36A-36D, 37A-37D, 38A-38E, 39A-39D, 40A-40D, 41A-41E, 42A-42D, 43A- 43E, 44A-44G, 45A-45E, 46A-46E, 47A-47G, or 48A-48E.

In an embodiment, the method comprises acquiring knowledge of the sequence (e.g., a mutation) of a CF target position in said subject.

In an embodiment, the method comprises acquiring knowledge of the sequence (e.g., a mutation) of a CF target position in said subject by sequencing the CFTR gene or SCNNIA gene or a portion of the CFTR gene or SCNNIA gene.

In an embodiment, the method comprises correcting a mutation at a CF target position in the CFTR gene.

In an embodiment, the method comprises correcting a mutation at a CF target position in the CFTR gene by HDR.

In an embodiment, the method comprises introducing a mutation at a CF target position in the SCNNIA gene.

In an embodiment, the method comprises introducing a mutation at a CF target position in the SCNNIA gene by NHEJ.

36

5535.1 When the method comprises correcting the mutation at a CF target position by HDR, a Cas9 of (b), at least one guide RNA, e.g., a guide RNA of (a) and a template nucleic acid of (d) are included in the contacting step.

In an embodiment, a cell of the subject is contacted ex vivo with (a), (b), (d) and optionally (c). In an embodiment, said cell is returned to the subject's body.

In an embodiment, a cell of the subject is contacted is in vivo with (a), (b) (d) and optionally (c)(i), further optionally (c)(ii), and still further optionally (c)(iii).

In an embodiment, the cell of the subject is contacted in vivo by inhalation delivery, e.g., via nebulizer, of (a), (b), (d) and optionally (c)(i), further optionally (c)(ii), and still further optionally (c)(iii).

In an embodiment, the cell of the subject is contacted in vivo by intravenous delivery of (a), (b), (d) and optionally (c)(i), further optionally (c)(ii), and still further optionally (c)(iii).

In an embodiment, the cell of the subject is contacted in vivo by intraparenchymal delivery of (a), (b), (d) and optionally (c)(i), further optionally (c)(ii), and still further optionally (c)(iii), e.g., to lung tissue or bronchial tree.

In an embodiment, the contacting step comprises contacting the subject with a nucleic acid, e.g., a vector, e.g., an AAV vector, described herein, e.g., a nucleic acid that encodes at least one of (a), (b), (d) and optionally (c)(i), further optionally (c)(ii), and still further optionally

(c) (iii).

In an embodiment, the contacting step comprises delivering to said subject said Cas9 molecule of (b), as a protein or mRNA, and a nucleic acid which encodes (a), a nucleic acid of

(d) and optionally (c)(i), further optionally (c)(ii), and still further optionally (c)(iii).

In an embodiment, the contacting step comprises delivering to the subject the Cas9 molecule of (b), as a protein or mRNA, the gRNA of (a), as an RNA, a nucleic acid of (d) and optionally the second gRNA of (c)(i), further optionally said third gRNA of (c)(ii), and still further optionally said fourth gRNA of (c)(iii), as an RNA.

In an embodiment, the contacting step comprises delivering to the subject the gRNA of (a), as an RNA, optionally said second gRNA of (c)(i), further optionally said third gRNA of (c)(ii), and still further optionally said fourth gRNA of (c)(iii), as an RNA, a nucleic acid that encodes the Cas9 molecule of (b), and a nucleic acid of (d).

37

5535.1 When the method comprises (1) introducing a mutation at a CF target position by NHEJ or (2) knocking down expression of the SCNN1A gene by targeting the promoter region, a Cas9 of (b) and at least one guide RNA, e.g., a guide RNA of (a) are included in the contacting step.

In an embodiment, a cell of the subject is contacted ex vivo with (a), (b) and optionally (c)(i), further optionally (c)(ii), and still further optionally (c)(iii). In an embodiment, said cell is returned to the subject's body.

In an embodiment, a population of cells from a subject is contacted ex vivo with (a), (b) and optionally (c)(i), further optionally (c)(ii), and still further optionally (c)(iii) and/or (d) to correct the F508del or G551D mutation in the CFTR gene and a second population of cells from the subject is contacted ex vivo with (a), (b) and optionally (c)(i), further optionally (c)(ii), and still further optionally (c)(iii), to introduce a mutation in the SCNN1A gene to knockout the SCNN1A gene. A mixture of the two cell populations may be returned to the subject's body to treat or prevent CF or CF-like disease.

In an embodiment, a cell of the subject is contacted is in vivo with (a), (b) and optionally (c)(i), further optionally (c)(ii), and still further optionally (c)(iii) and/or (d). In an embodiment, the cell of the subject is contacted in vivo by inhalation delivery, e.g., via nebulizer, of (a), (b) and optionally (c)(i), further optionally (c)(ii), and still further optionally (c)(iii) and/or (d). In an embodiment, the cell of the subject is contacted in vivo by intravenous delivery of (a), (b) and optionally (c)(i), further optionally (c)(ii), and still further optionally (c)(iii) and/or (d). In an embodiment, the cell of the subject is contacted in vivo by intraparenchymal delivery of (a), (b) and optionally (c)(i), further optionally (c)(ii), and still further optionally (c)(iii) and/or (d), e.g., to lung tissue or bronchial tree.

In an embodiment, contacting comprises contacting the subject with a nucleic acid, e.g., a vector, e.g., an AAV vector, described herein, e.g., a nucleic acid that encodes at least one of (a), (b), and optionally (c)(i), further optionally (c)(ii), and still further optionally (c)(iii) and/or (d).

In an embodiment, contacting comprises delivering to said subject said Cas9 molecule of (b), as a protein or mRNA, and a nucleic acid which encodes (a) and optionally (c)(i), further optionally (c)(ii), and still further optionally (c)(iii) and/or (d).

In an embodiment, contacting comprises delivering to the subject the Cas9 molecule of (b), as a protein or mRNA, the gRNA of (a), as an RNA, and optionally the second gRNA of

38

5535.1 (c) (i), further optionally said third gRNA of (c)(ii), and still further optionally said fourth gRNA of (c)(iii), as an RNA, and further optionally the template nucleic acid of (d) as a DNA.

In an embodiment, contacting comprises delivering to the subject the gRNA of (a), as an RNA, optionally said second gRNA of (c)(i), further optionally said third gRNA of (c)(ii), and still further optionally said fourth gRNA of (c)(iii), as an RNA, and a nucleic acid that encodes the Cas9 molecule of (b), and optionally a nucleic acid that encodes the template nucleic acid of

(d) .

In another aspect, disclosed herein is a reaction mixture comprising a gRNA molecule, a nucleic acid, or a composition described herein, and a cell, e.g., a cell from a subject having, or likely to develop CF or CF-like disease, or a subject having a mutation at a CF target position in the CFTR gene, or a cell from a subject which would benefit from having a mutation at a CF target position in the SCNN1A gene.

In another aspect, disclosed herein is a kit comprising, (a) a gRNA molecule described herein, or nucleic acid that encodes the gRNA, and one or more of the following:

(b) a Cas9 molecule, e.g., a Cas9 molecule described herein, or a nucleic acid or mRNA that encodes the Cas9;

(c)(i) a second gRNA molecule, e.g., a second gRNA molecule described herein or a nucleic acid that encodes (c)(i);

(c)(ii) a third gRNA molecule, e.g., a second gRNA molecule described herein or a nucleic acid that encodes (c)(ii);

(c) (iii) a fourth gRNA molecule, e.g., a second gRNA molecule described herein or a nucleic acid that encodes (c)(iii); and

(d) a template nucleic acid, e.g, a template nucleic acid described herein.

In an embodiment, the kit comprises nucleic acid, e.g., an AAV vector, that encodes one or more of (a), (b), (c)(i), (c)(ii), (c)(iii) and (d).

In another aspect, disclosed herein is non-naturally occurring template nucleic acid described herein.

In yet another aspect, disclosed herein is a gRNA molecule, e.g., a gRNA molecule described herein, for use in treating or preventing CF or CF-like disease in a subject, e.g., in accordance with a method of treating or preventing CF or CF-like disease as described herein.

39

5535.1 In an embodiment, the gRNA molecule in used in combination with a Cas9 molecule, e.g., a Cas9 molecule described herein. Additionally or alternatively, in an embodiment, the gRNA molecule is used in combination with a second, third and/or fouth gRNA molecule, e.g., a second, third and/or fouth gRNA molecule described herein.

In still another aspect, disclosed herein is use of a gRNA molecule, e.g., a gRNA molecule described herein, in the manufacture of a medicament for treating or preventing CF or CF-like disease in a subject, e.g., in accordance with a method of treating or preventing CF or CF-like disease as described herein.

In an embodiment, the medicament comprises a Cas9 molecule, e.g., a Cas9 molecule described herein. Additionaly or alternatively, in an embodiment, the medicament comprises a second, third and/or fouth gRNA molecule, e.g., a second, third and/or fouth gRNA molecule described herein.

The gRNA molecules and methods, as disclosed herein, can be used in combination with a governing gRNA molecule. As used herein, a governing gRNA molecule refers to a gRNA molecule comprising a targeting domain which is complementary to a target domain on a nucleic acid that encodes a component of the CRISPR/Cas system introduced into a cell or subject. For example, the methods described herein can further include contacting a cell or subject with a governing gRNA molecule or a nucleic acid encoding a governing molecule. In an embodiment, the governing gRNA molecule targets a nucleic acid that encodes a Cas9 molecule or a nucleic acid that encodes a target gene gRNA molecule. In an embodiment, the governing gRNA comprises a targeting domain that is complementary to a target domain in a sequence that encodes a Cas9 component, e.g., a Cas9 molecule or target gene gRNA molecule. In an embodiment, the target domain is designed with, or has, minimal homology to other nucleic acid sequences in the cell, e.g., to minimize off-target cleavage. For example, the targeting domain on the governing gRNA can be selected to reduce or minimize off-target effects. In an embodiment, a target domain for a governing gRNA can be disposed in the control or coding region of a Cas9 molecule or disposed between a control region and a transcribed region. In an embodiment, a target domain for a governing gRNA can be disposed in the control or coding region of a target gene gRNA molecule or disposed between a control region and a transcribed region for a target gene gRNA. While not wishing to be bound by theory, in an embodiment, it is believed that altering, e.g., inactivating, a nucleic acid that encodes a Cas9 molecule or a

40

5535.1 nucleic acid that encodes a target gene gRNA molecule can be effected by cleavage of the targeted nucleic acid sequence or by binding of a Cas9 molecule/governing gRNA molecule complex to the targeted nucleic acid sequence.

The compositions, reaction mixtures and kits, as disclosed herein, can also include a governing gRNA molecule, e.g., a governing gRNA molecule disclosed herein.

Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, suitable methods and materials are described below. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting.

Headings, including numeric and alphabetical headings and subheadings, are for organization and presentation and are not intended to be limiting.

Other features and advantages of the invention will be apparent from the detailed description, drawings, and from the claims.

BRIEF DESCRIPTION OF THE DRAWINGS Figs. 1A-1I are representations of several exemplary gRNAs.

Fig. 1A depicts a modular gRNA molecule derived in part (or modeled on a sequence in part) from Streptococcus pyogenes (S. pyogenes) as a duplexed structure (SEQ ID NOS: 42 and 43, respectively, in order of appearance);

Fig. IB depicts a unimolecular (or chimeric) gRNA molecule derived in part from S. pyogenes as a duplexed structure (SEQ ID NO: 44);

Fig. 1C depicts a unimolecular gRNA molecule derived in part from S. pyogenes as a duplexed structure (SEQ ID NO: 45);

Fig. ID depicts a unimolecular gRNA molecule derived in part from S. pyogenes as a duplexed structure (SEQ ID NO: 46);

Fig. IE depicts a unimolecular gRNA molecule derived in part from S. pyogenes as a duplexed structure (SEQ ID NO: 47);

41

5535.1 Fig. IF depicts a modular gRNA molecule derived in part from Streptococcus thermophilus (S. thermophilus) as a duplexed structure (SEQ ID NOS: 48 and 49, respectively, in order of appearance);

Fig. 1G depicts an alignment of modular gRNA molecules of S. pyogenes and S.

thermophilus (SEQ ID NOS: 50-53, respectively, in order of appearance).

Figs. 1H-1I depicts additional exemplary structures of unimolecular gRNA molecules. Fig. 1H shows an exemplary structure of a unimolecular gRNA molecule derived in part from S. pyogenes as a duplexed structure (SEQ ID NO: 45). Fig. II shows an exemplary structure of a unimolecular gRNA molecule derived in part from S. aureus as a duplexed structure (SEQ ID NO: 40).

Figs. 2A-2G depict an alignment of Cas9 sequences from Chylinski et al. (RNA Biol. 2013; 10(5): 726-737). The N-terminal RuvC-like domain is boxed and indicated with a "Y". The other two RuvC-like domains are boxed and indicated with a "B". The HNH-like domain is boxed and indicated by a "G". Sm: S. mutans (SEQ ID NO: 1); Sp: S. pyogenes (SEQ ID NO: 2); St: S. thermophilus (SEQ ID NO: 3); Li: L. innocua (SEQ ID NO: 4). Motif: this is a motif based on the four sequences: residues conserved in all four sequences are indicated by single letter amino acid abbreviation; "*" indicates any amino acid found in the corresponding position of any of the four sequences; and "-" indicates any amino acid, e.g., any of the 20 naturally occurring amino acids, or absent.

Figs. 3A-3B show an alignment of the N-terminal RuvC-like domain from the Cas9 molecules disclosed in Chylinski et al (SEQ ID NOS: 54-103, respectively, in order of appearance). The last line of Fig. 3B identifies 4 highly conserved residues.

Figs. 4A-4B show an alignment of the N-terminal RuvC-like domain from the Cas9 molecules disclosed in Chylinski et al. with sequence outliers removed (SEQ ID NOS: 104-177, respectively, in order of appearance). The last line of Fig. 4B identifies 3 highly conserved residues.

Figs. 5A-5C show an alignment of the HNH-like domain from the Cas9 molecules disclosed in Chylinski et al (SEQ ID NOS: 178-252, respectively, in order of appearance). The last line of Fig. 5C identifies conserved residues.

Figs. 6A-6B show an alignment of the HNH-like domain from the Cas9 molecules disclosed in Chylinski et al. with sequence outliers removed (SEQ ID NOS: 253-302,

42

5535.1 respectively, in order of appearance). The last line of Fig. 6B identifies 3 highly conserved residues.

Figs. 7A-7B depict an alignment of Cas9 sequences from S. pyogenes and Neisseria meningitidis (N. meningitidis). The N-terminal RuvC-like domain is boxed and indicated with a "Y". The other two RuvC-like domains are boxed and indicated with a "B". The HNH-like domain is boxed and indicated with a "G". Sp: S. pyogenes; Nm: N. meningitidis. Motif: this is a motif based on the two sequences: residues conserved in both sequences are indicated by a single amino acid designation; "*" indicates any amino acid found in the corresponding position of any of the two sequences; "-" indicates any amino acid, e.g., any of the 20 naturally occurring amino acids, and "-" indicates any amino acid, e.g., any of the 20 naturally occurring amino acids, or absent.

Fig. 8 shows a nucleic acid sequence encoding Cas9 of N. meningitidis (SEQ ID NO: 303). Sequence indicated by an "R" is an SV40 NLS; sequence indicated as "G" is an HA tag; and sequence indicated by an "O" is a synthetic NLS sequence; the remaining (unmarked) sequence is the open reading frame (ORF).

Figs. 9A and 9B are schematic representations of the domain organization of S. pyogenes Cas 9. Fig. 9A shows the organization of the Cas9 domains, including amino acid positions, in reference to the two lobes of Cas9 (recognition (REC) and nuclease (NUC) lobes). Fig. 9B shows the percent homology of each domain across 83 Cas9 orthologs.

DETAILED DESCRIPTION

Definitions

"CF target mutant position", as used herein, refers to a target position in the CFTR gene, which, if mutated, can result in a mutant protein and give rise to CF or CF-like disease. In an embodiment, the target position comprises one, two, or three nucleotides. In an embodiment, the CF target mutant position is a position in the CFTR gene at which a change can give rise to a mutant protein having a mutation at F508, e.g., F508del. In an embodiment, the CF target mutant position is a position in the CFTR gene at which a change can give rise to a mutant protein having a mutation at G551, e.g., G551D. In an embodiment, the CF target mutant position is a position in the CFTR gene at which a change can give rise to a mutant protein having a mutation at G542, e.g., G542X, in the CFTR protein, which corresponds to c. l624G>T

43

5535.1 in the CFTR gene. In an embodiment, the CF target mutant position is a position in the CFTR gene at which a change can give rise to a mutant protein having a mutation at N1303, e.g., N1303K, in the CFTR protein, which corresponds to c.3909C>G in the CFTR gene. In an embodiment, the CF target mutant position is a position in the CFTR gene at which a change can give rise to a mutant protein having a mutation at Rl 17, e.g., Rl 17H, in the CFTR protein, which corresponds to c.350G>A in the CFTR gene. In an embodiment, the CF target mutant position is a position in the CFTR gene at which a change can give rise to a mutant protein having a mutation at W1282, e.g., W1282X, in the CFTR protein, which corresponds to c. c.3846G>A in the CFTR gene. In an embodiment, the CF target mutant position is a position in the CFTR gene at which a change can give rise to a mutant protein having a mutation at R553, e.g., R553X, in the CFTR protein, which corresponds to c. l657C>T in the CFTR gene. In an embodiment, the CF target mutant position is c.3717+12191, also known as c.3849+10kb, which corresponds to 3717+12191C>T in the CFTR gene. In an embodiment, the CF target mutant position is c.2657+5, also known as c.2789+5, which corresponds to 2657+5G>A in the CFTR gene. In an embodiment, the CF target mutant position is c.3140-26, also known as c.3272-26, which corresponds to c.3140-26 A>G in the CFTR gene. In an embodiment, the CF target mutant position is a position in the SCNNIA gene at which a change can give rise to a mutant protein having a mutation at VI 14, which corresponds to VI 141 in the SCNNIA gene.

"CF target knockout position", as used herein, refers to a position in the CFTR and/or SCNNIA gene, which if altered by NHEJ-mediated alteration, results in alleviation of a symptom of CF or CF-like disease. In an embodiment, the alteration restores expression of functional CFTR gene product. In an embodiment, the position is in the CFTR non-coding region, e.g., an intronic region (e.g., the alternation corrects a cryptic splice site). In an embodiment, the alteration results in reduction or elimination of expression of functional SCNNIA gene product. In an embodiment, the position is in the SCNNIA coding region, e.g., an early coding region.

"CF target knockdown position", as used herein, refers to a position in the SCNNIA gene, which if targeted, e.g., by an eiCas9 molecule or an eiCas9 fusion described herein, results in reduction or elimination of expression of functional SCNNIA gene product. In an embodiment, the transcription of the SCNNIA gene is reduced or eliminated. In another embodiment, the chromatin structure of the SCNNIA gene is altered. In an embodiment, the position is in the

SCNNIA early coding region sequence. In an embodiment, a position in early coding region of

44

5535.1 the SCNN1A gene is targeted by an enzymatically inactive Cas9 (eiCas9) molecule or an eiCas9- fusion protein, as described herein.

"CF target knockin position", as used herein, refers to a sequence, which if modified by the insertion of CFTR sequence, results in an optimization of CFTR activity, e.g., by resulting in a CFTR sequence that encodes a protein having wild type activity. Exemplary CF target knockin position include: CFTR sequence within intron 2, into which, e.g., can be introduced CFTR sequence that codes for CFTR exons 3-27; and sequence within CFTR intron 10, into which sequence that codes for CFTR exons 11-27 can be introduced. In an embodiment, a CF target knockin position includes CFTR intronic sequence between a second and a third exon (e.g., intron 2), and CFTR sequence encoding the third exon through the final exon (exon 27), is introduced, resulting in a CFTR sequence that is free of one or more cryptic splice sites and that encodes a CFTR protein having wild type activity. In an embodiment, a CF target knockin position, is a position which is upstream of a mutation, or upsteam of an intron having a mutation, and introduction of wild-type CFTR sequence results in a CFTR sequence that is free of the mutation. In an embodiment the CF target knockin position is in CFTR intronic sequence: between exon2 and exon 3; or between exon 10 and exon 11. In an embodiment, the resulting CFTR sequence comprises subject sequence upstream from the CF target knockin position and newly introduced sequence downstream from the CF target knockin position, which taken together, encode a CFTR protein having wild type activity. In an embodiment, the point of insertion is 3' to a splice donor site and 5' from a splice acceptor site. In an embodiment, CFTR sequence encoding exons 3-27 is inserted under control of the promoter, e.g., at the transcription start site. In an embodiment, CFTR sequence introduced can exclude introns, e.g., a sequence encoding exons, but without introns, is inserted, e.g., CFTR CDNA sequence is introduced.

"CF target position", as used herein, refers to a CF target mutant position, CF target knockout position, CF target knockdown position, and/or CF target knockin position, as described herein.

"Domain", as used herein, is used to describe segments of a protein or nucleic acid. Unless otherwise indicated, a domain is not required to have any specific functional property.

Calculations of homology or sequence identity between two sequences (the terms are used interchangeably herein) are performed as follows. The sequences are aligned for optimal comparison purposes (e.g., gaps can be introduced in one or both of a first and a second amino

45

5535.1 acid or nucleic acid sequence for optimal alignment and non-homologous sequences can be disregarded for comparison purposes). The optimal alignment is determined as the best score using the GAP program in the GCG software package with a Blossum 62 scoring matrix with a gap penalty of 12, a gap extend penalty of 4, and a frame shift gap penalty of 5. The amino acid residues or nucleotides at corresponding amino acid positions or nucleotide positions are then compared. When a position in the first sequence is occupied by the same amino acid residue or nucleotide as the corresponding position in the second sequence, then the molecules are identical at that position. The percent identity between the two sequences is a function of the number of identical positions shared by the sequences.

"Governing gRNA molecule", as used herein, refers to a gRNA molecule that comprises a targeting domain that is complementary to a target domain on a nucleic acid that comprises a sequence that encodes a component of the CRISPR/Cas system that is introduced into a cell or subject. A governing gRNA does not target an endogenous cell or subject sequence. In an embodiment, a governing gRNA molecule comprises a targeting domain that is complementary with a target sequence on: (a) a nucleic acid that encodes a Cas9 molecule; (b) a nucleic acid that encodes a gRNA which comprises a targeting domain that targets the CFTR or SCNN1A gene (a target gene gRNA); or on more than one nucleic acid that encodes a CRISPR/Cas component, e.g., both (a) and (b). In an embodiment, a nucleic acid molecule that encodes a CRISPR/Cas component, e.g., that encodes a Cas9 molecule or a target gene gRNA, comprises more than one target domain that is complementary with a governing gRNA targeting domain. While not wishing to be bound by theory, in an embodiment, it is believed that a governing gRNA molecule complexes with a Cas9 molecule and results in Cas9 mediated inactivation of the targeted nucleic acid, e.g., by cleavage or by binding to the nucleic acid, and results in cessation or reduction of the production of a CRISPR/Cas system component. In an embodiment, the Cas9 molecule forms two complexes: a complex comprising a Cas9 molecule with a target gene gRNA, which complex will alter the CFTR or SCNN1A gene; and a complex comprising a Cas9 molecule with a governing gRNA molecule, which complex will act to prevent further production of a CRISPR/Cas system component, e.g., a Cas9 molecule or a target gene gRNA molecule. In an embodiment, a governing gRNA molecule/Cas9 molecule complex binds to or promotes cleavage of a control region sequence, e.g., a promoter, operably linked to a sequence that encodes a Cas9 molecule, a sequence that encodes a transcribed region, an exon, or an

46

5535.1 intron, for the Cas9 molecule. In an embodiment, a governing gRNA molecule/Cas9 molecule complex binds to or promotes cleavage of a control region sequence, e.g., a promoter, operably linked to a gRNA molecule, or a sequence that encodes the gRNA molecule. In an embodiment, the governing gRNA, e.g., a Cas9-targeting governing gRNA molecule, or a target gene gRNA- targeting governing gRNA molecule, limits the effect of the Cas9 molecule/target gene gRNA molecule complex-mediated gene targeting. In an embodiment, a governing gRNA places temporal, level of expression, or other limits, on activity of the Cas9 molecule/target gene gRNA molecule complex. In an embodiment, a governing gRNA reduces off-target or other unwanted activity. In an embodiment, a governing gRNA molecule inhibits, e.g., entirely or substantially entirely inhibits, the production of a component of the Cas9 system and thereby limits, or governs, its activity.

"Modulator", as used herein, refers to an entity, e.g., a drug, that can alter the activity (e.g., enzymatic activity, transcriptional activity, or translational activity), amount, distribution, or structure of a subject molecule or genetic sequence. In an embodiment, modulation comprises cleavage, e.g., breaking of a covalent or non-covalent bond, or the forming of a covalent or non- covalent bond, e.g., the attachment of a moiety, to the subject molecule. In an embodiment, a modulator alters the, three dimensional, secondary, tertiary, or quaternary structure, of a subject molecule. A modulator can increase, decrease, initiate, or eliminate a subject activity.

"Large molecule", as used herein, refers to a molecule having a molecular weight of at least 2, 3, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100 kD. Large molecules include proteins, polypeptides, nucleic acids, biologies, and carbohydrates.

"Polypeptide", as used herein, refers to a polymer of amino acids having less than 100 amino acid residues. In an embodiment, it has less than 50, 20, or 10 amino acid residues.

"Reference molecule", e.g., a reference Cas9 molecule or reference gRNA, as used herein, refers to a molecule to which a subject molecule, e.g., a subject Cas9 molecule of subject gRNA molecule, e.g., a modified or candidate Cas9 molecule is compared. For example, a Cas9 molecule can be characterized as having no more than 10% of the nuclease activity of a reference Cas9 molecule. Examples of reference Cas9 molecules include naturally occurring unmodified Cas9 molecules, e.g., a naturally occurring Cas9 molecule such as a Cas9 molecule of S.

pyogenes, S. aureus or S. thermophilus. In an embodiment, the reference Cas9 molecule is the naturally occurring Cas9 molecule having the closest sequence identity or homology with the

47

5535.1 Cas9 molecule to which it is being compared. In an embodiment, the reference Cas9 molecule is a sequence, e.g., a naturally occurring or known sequence, which is the parental form on which a change, e.g., a mutation has been made.

"Replacement", or "replaced", as used herein with reference to a modification of a molecule does not require a process limitation but merely indicates that the replacement entity is present.

"Small molecule", as used herein, refers to a compound having a molecular weight less than about 2 kD, e.g., less than about 2 kD, less than about 1.5 kD, less than about 1 kD, or less than about 0.75 kD.

"Subject", as used herein, may mean either a human or non-human animal. The term includes, but is not limited to, mammals (e.g., humans, other primates, pigs, rodents (e.g., mice and rats or hamsters), rabbits, guinea pigs, cows, horses, cats, dogs, sheep, and goats). In an embodiment, the subject is a human. In other embodiments, the subject is poultry.

"Treat", "treating" and "treatment", as used herein, mean the treatment of a disease in a mammal, e.g., in a human, including (a) inhibiting the disease, i.e., arresting or preventing its development; (b) relieving the disease, i.e., causing regression of the disease state; and (c) curing the disease.

"X" as used herein in the context of an amino acid sequence, refers to any amino acid (e.g., any of the twenty natural amino acids) unless otherwise specified. Cystic Fibrosis and CF-like Disease

Cystic fibrosis (CF) is an autosomal recessive hereditary disease caused by defects in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The CFTR gene encodes a cAMP-gated channel that is involved in chloride and bicarbonate transport. It regulates sodium transport through inhibition of the epithelial sodium channel, which is encoded by the SCNN1A gene. CFTR is expressed on the apical surface of epithelial cells in the airway, gastrointestinal tract, reproductive tract, sweat glands and submucosal glands.

Subjects having CF or CF-like disease may present at birth or in early infancy with pancreatic insufficiency. Pancreatic dysfunction leads to malabsorption of fat and fat-soluble vitamins, which causes poor growth as well as gallstones and biliary disease. The lung manifestations of the disease can be more severe but may present slightly after pancreatic manifestations, in infancy or early childhood. Aberrant chloride and sodium transport due to

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5535.1 decreased CFTR activity causes lowered apical surface fluid levels in the lungs, which leads to "sticky" mucous and lower airway obstruction. Subjects having CF or CF-like disease suffer from frequent infections due to inability to clear mucous. Local inflammatory mediators try to clear the infection but have difficulty. The triad of inflammation, infection and obstruction leads to progressive destruction of the lung parenchyma. Eventually, many subjects having CF or CF- like disease die in their late 30' s due to respiratory failure.

Current treatments for CF or CF-like disease can increase the life expectancy of subjects with CF or CF-like disease. These treatments delay lung destruction and slow disease progression. These treatments do not reverse the damage to the lungs or cure CF or CF-like disease. Subjects having CF or CF-like disease eventually suffer from end-stage lung disease.

Treatments for the pulmonary manifestations of CF or CF-like disease include:

antibiotics (oral, inhaled and intravenous), CFTR modulators (including CFTR potentiators), DNase, chest physiotherapy to loosen secretions and anti-inflammatory therapeutics. Treatment of the gastrointestinal manifestations includes supplemental gut soluble vitamins, high calorie diet and oral pancreatic enzymes. Subjects who develop diabetes are treated with insulin injections or an insulin pump. At the end stage, patients may benefit from lung transplant. Lung transplant may be combined with liver and/or pancreatic transplant. The average life expectancy for subjects having CF or CF-like disease is nearing 40 years of age.

Methods and compositions discussed herein provide for the treatment and prevention of Cystic Fibrosis (CF) and CF-like disease. The approach described herein aims to restore CFTR channel function, restore chloride, bicarbonate and/or sodium balance, and/or decrease mucous viscosity within the lungs, airways, gastrointestinal tract and reproductive tract.

CFTR modulators (both approved and in development) improve the functioning of mutant CFTR. These therapeutics improve CFTR functioning but do not return functionality to wild type levels. The approach described herein is expected to restore CFTR function through complete correction of the gene.

Gene therapy approaches are in development that deliver the CFTR channel gene to the lungs of CF patients. However, gene therapy may require constant readministration over the course of the lifetime of a subject due to high cell turnover in target epithelial cells. The approach described herein is expected to restore CFTR function and/or ameliorate SCNN1A disinhibition permanently through one, two or several doses.

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5535.1 The CFTR gene encodes a 180-kDA cAMP-gated chloride (C1-) channel. The channel has six transmembrane spanning domains and is expressed by epithelial cells, lymphocytes and cardiac myocytes. The CFTR regulates the viscosity of mucous through its activity in the epithelial cells of the lungs, gastrointestinal tract and reproductive tract. Mutations in the CFTR result in decreased CFTR activity. Decreased CFTR activity can lead to aberrant ion transport, which gives rise to various disease symptoms in the lungs and other tissues, such as

accumulation of sticky mucus, airway obstruction, infection and inflammation. Correction of CFTR mutations will ameliorate or cure lung, gastrointestinal and/or reproductive symptoms of CF.

The SCNN1A gene encodes the alpha subunit of the epithelial sodium channel (ENaC).

The channel, comprised of alpha, beta and gamma subunits, regulates sodium transport into epithelial cells, including the epithelium of the lungs, sweat glands and kidneys. Mutations in the SCNN1A gene, (e.g. Vail 14ILE) have been shown to cause CF-like disease, characterized by pulmonary disease, including bronchiectasis. Mutations in SCNN1A also cause

pseudohypoaldosteronism, a severe disease of the kidney. Pseudohypoaldosteronism is due to defective sodium transport within kidney epithelial cells; it is not caused by defective sodium transport in other tissues. The methods described herein include the targeted knockout of SCNN1A in the lung, gastrointestinal tract and/or reproductive tract. The methods described herein will not target kidney epithelium and will avoid the negative consequences of SCNN1A mutations within the kidney epithelium. One mutation in the SCNN1A gene, a 1477T>G substitution (W493R) has been identified in subjects who also have a mutation in CFTR. This mutation is associated with a severe CF phenotype, including severe bronchiectasis, chronic bronchitis and/or severe gastrointestinal symptoms. This mutation has been found to be associated with 4-fold overactivity of the ENaC channel (Azad et al., 2009; Human Mutation 30: 1093-1103). Overactivity of the SCNNlA-encoded ENaC channel can contribute to CF and CF- like disease. In all subjects, the CFTR is involved in inhibition of ENaC. CFTR mutations in subjects with CF or CF-like disease leads to ENaC disinhibition, leading to overactivity of the ENaC channel. ENaC overactivity can lead to further reduction in viscosity of mucous in CF or CF-like disease subjects, as more sodium is absorbed at the apical surface of epithelial cells, followed by increased fluid absorption from the mucous layer within the lung (Baker et al., 2012; Medicine & Science in Sports and Exercise 44(12): 2315-2321). Increased fluid absorption from

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5535.1 the mucous layer reduces mucous viscosity. Inhibition of ENaC through SCNNIA knockout and/or knockdown in subjects with CF or CF-like disease can ameliorate the symptoms of CF or CF-like disease.

One common mutation in the CFTR gene is a deletion of the three nucleotides encoding Phenylalanine (F) at position 508 of the CFTR protein F508del (also sometime referred to herein as "F508del" or "delF508"). This mutation is the causative mutation in approximately two-thirds of CF cases. The remaining cases are caused by at least 1000 different mutations, many of which cause a less severe form of the disease.

Overactivity of the SCNNIA gene has been shown to contribute to bronchiectasis, bronchitis, and gastrointestinal symptoms in subjects with CF and in subjects with CF-like disease. In another aspect, methods and compositions discussed herein may be used to alter the SCNNIA gene (also known as sodium channel, non-voltage-gated 1 alpha subunit; amiloride- sensitive epithelial sodium channel alpha subunit; BESC2; ENaCa; SCNEA; SCNN1;

ENaCalpha) to treat or prevent CF or CF-like disease, by targeting the SCNNIA gene, e.g., the non-coding or coding regions, e.g., a promoter region, or a transcribed sequence, e.g., intronic or exonic sequence. In an embodiment, the target position is VI 14, which corresponds to VI 141 in the SCNNIA gene. SCNNIA encodes an epithelial sodium channel, ENaC, that is negatively regulated by CFTR. In subjects with CFTR mutations, knocking out or knocking down the SCNNIA gene in certain cells will reduce or reverse the effect of defective CFTR. In subjects with no CFTR mutations but CF-like disease caused by SCNNIA mutations or other mechanisms, knocking out or knocking down the SCNNIA gene in certain cells will improve the viscosity of mucous and ameliorate disease.

Methods to Treat or Prevent Cystic Fibrosis and Cystic Fibrosis-like Disease

Correction of the CFTR mutation (e.g., F508 deletion, e.g., G551D substitution, e.g.,

G542X nonsense mutation, e.g., N1303K substitution, e.g., R117H substitution, e.g., W1282X nonsense mutation, e.g., R553X nonsense mutation, e.g., 3849+10kbC>T substitution, e.g., 2789+5G>A substitution, e.g., 3273-26A>G substitution) or inactivationor knockdown of the SCNNIA gene, e.g., using the methods disclosed herein, can ameliorate the disease. In an embodiment, the method leads to normalized ion transport, less viscous mucous, and/or reduced mucous plugging and inflammation, e.g., early in the disease course. In an embodiment, the

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5535.1 method results in fewer infections, decreased lung tissue destruction, and/or slowing in progression of disease. In an embodiment, the method improves mucous production and/or reduce frequency and/or length of infections, e.g., in later stages of the disease. In an embodiment, the method reduces or prevents further damage by ameliorating the triad of inflammation, infection and obstruction. In an embodiment, the method delays progression of the disease. In an embodiment, the method reduces or prevents further damage by ameliorating the triad of inflammation, infection and obstruction. In an embodiment, the method leads to normalized ion transport, and restoration of fertility. In an embodiment, the method leads to normalized ion transport, and improved gastrointestinal motility, absorption, and/or function.

Disclosed herein are the approaches to treat or prevent CF or CF-like disease, using the compositions and methods described herein.

While not wishing to be bound by theory, it is believed that, in an embodiment described herein, the CFTR channel is corrected and chloride and bicarbonate balance restored, e.g., within the lung, e.g., within the airway, e.g., within the gastrointestinal tract, e.g., within the

reproductive tract, e.g., in the hepatobiliary epithelium, e.g. in the pancreas. CFTR modulators (both approved and in development) improve the functioning of mutant CFTR. These therapeutics improve CFTR functioning but do not return functionality to wild type levels.

In an embodiment, the approach described herein restores CFTR function through complete correction of the CFTR gene. In another embodiment, the approach described herein inactivates the SCNN1A gene, e.g., in the pulmonary epithelium, e.g., in the airway epithelium, e.g., in the gastrointestinal epithelium, e.g. in the reproductive epithelium, e.g., in the

hepatobiliary epithelium, e.g. in the pancreatic ducts, in order to inhibit the abnormal sodium ion transport associated with reduced CFTR activity and/or in order to inhibit abnormal sodium ion transport associated with overactive ENaC activity. In an embodiment, these two approaches are combined to treat or prevent CF or CF-like disease. In an embodiment, the approaches described herein provide advantages over CFTR modulators.

It is contemplated that the compositions disclosed herein may be administered once or more than once (e.g., 2, 3, 4, 5, or more times) to correct a mutation in the CFTR gene or to inactivate or knock-down the SCNN1A gene. It is further contemplated that when the compositions disclosed herein are administered more than one time that the multiple

administrations are intended to increase the number of cells (e.g., the number of cells in the subject) containing the corrected form of the CFTR gene and/or the inactivated/knocked-down form of the SCNNIA gene, thereby increasing the effectiveness of the treatment.

The methods of treatment described herein can be initiated for subjects at all stages of the disease. In an embodiment, the treatment is initiated after disease onset, e.g., as the subject presents with lung infections, wheezing and obstructed airways, and/or pancreatic insufficiency, decreased gastrointestinal function, malabsorption, and/or infertility. While not wishing to be bound by theory, in an embodiment, repair of the CFTR gene or inactivation/knock-down of the SCNNIA gene after disease onset but early in the disease course reduces or prevents progression of the disease. In an embodiment, the method comprises treating a subject with advanced disease. In an embodiment, the method reduces or prevents further progression of symptoms, with or without reversing pathology.

In an embodiment, the treatment is initiated prior to disease onset. In another embodiment, the treatment is initiated at an early stage of the disease, e.g., before the subject has noticed any decline in function or symptoms.

In an embodiment, treatment is initiated in utero.

In an embodiment, treatment is initiated after birth.

In an embodiment, treatment is initiated prior to the age of 1.

In an embodiment, treatment is initiated prior to the age of 2.

In an embodiment, treatment is initiated prior to the age of 5.

In an embodiment, treatment is initiated prior to the age of 10.

In an embodiment, the subject has tested positive for a mutation in the CFTR gene, e.g., a mutation described herein.

In an embodiment, the subject has tested positive for a mutation in the SCNNIA gene, e.g., a mutation described herein.

In an embodiment, the treatment is initiated at appearance of a symptom of CF or CF-like disease, e.g., any of the following symptoms: frequent lung infections, chronic cough, sputum production, or chronic wheeze. In an embodiment, the subject has a positive "sweat test" or elevated sweat Chloride indicating dysfunction of the CFTR channel and/or overactivity of the SCNNIA channel. In an embodiment, the subject has an elevated sweat Chloride, bronchiectasis and is found to have no mutation in the CFTR gene. In an embodiment, the treatment is initiated if the subject is tested positive for a defect, e.g., a genetic defect, in the CFTR gene.

In an embodiment, the treatment is initiated if the subject is tested positive for a defect, e.g., a genetic defect, in the SCNN1A gene.

In an embodiment, the treatment is initiated if a family member of the subject has been diagnosed with CF or CF-like disease. In an embodiment, the subject has a symptom or sign of CF or CF-like disease. In an embodiment, the subject has a mutation in the CFTR gene, e.g., a mutation described herein.

In an embodiment, the treatment is initiated at the appearance of any of the following findings consistent with CF or CF-like disease, including but not limited to, obstructive lung disease on lung function tests; persistent colonization with B. cepacia, P. aeruginosa and S. aureus and other CF-related pathogens; chronic radiologic abnormalities on chest x-ray; or chronic sinusitis.

In an embodiment, the method comprises initiating treatment at the appearance of any of the following gastrointestinal findings consistent with CF or CF-like disease, including but not limited to: failure to thrive, steatorrhea, hypoproteinemia, vitamin deficiency due to fat- soluble vitamin malabsorption, meconium ileus, rectal prolapse, malabsorption, pancreatic insufficiency, pancreatitis, or chronic hepatobiliary disease. Evidence of chronic hepatobiliary disease can include, e.g., elevated transaminases and/or hyperbilirubinemia.

In an embodiment, a cell is treated ex vivo. In an embodiment, the cell is returned to the subject.

In an embodiment, it is contemplated herein that a population of cells from a subject may be contacted ex vivo to correct a mutation in the CFTR gene, e.g., F508del, e.g., G542X, e.g., G551D, e.g., N1303K, e.g., R117H, e.g., W1282X, e.g., R553X, e.g., 3849+10kbC>T, e.g., 2789+5G>A, e.g., 3273-26A>G, and a second population of cells from the subject is contacted ex vivo to introduce a mutation in the SCNN1A gene to knockout or knockdown SCNN1A. A mixture of the two cell populations may be returned to the subject's body to prevent or treat CF or CF-like disease.

In an embodiment, the cell is harvested from epidermis, pulmonary tree, hepatobiliary tree, gastrointestinal tract, reproductive tract, or other organ. In an embodiment, the cell is reprogrammed to an induced pluripotent stem (iPS) cell. In an embodiment, the iPS cell is differentiated into airway epithelium, pulmonary epithelium, submucosal glands, submucosal ducts, biliary epithelium, gastrointestinal epithelium, pancreatic duct cells, reproductive epithelium, epidydimal cells, and/or cells of the hepatobiliary tree, e.g., clara cells, e.g., ciliated cells, e.g., goblet cells, e.g., basal cells, e.g., acinus cells, e.g., bronchioalveolar stem cell e.g., lung epithelial cells, e.g., nasal epithelial cells, e.g., tracheal epithelial cells, e.g., bronchial epithelial cells, e.g., enteroendocrine cells, e.g., Brunner's gland cells, e.g., epididymal epithelium. In an embodiment, the CFTR gene in the cell is corrected with the method described herein. In an embodiment, the SCNNIA gene in the cell is corrected with the method described herein. In an embodiment, the CFTR gene and the SCNNIA gene in the cell is corrected with the method described herein. In an embodiment, the cell is re-introduced into an appropriate location in the subject, e.g., airway, pulmonary tree, bile duct system, gastrointestinal tract, pancreas, hepatobiliary tree, and/or reproductive tract.

In an embodiment, an autologous stem cell can be treated ex vivo, differentiated into airway epithelium, pulmonary epithelium, submucosal glands, submucosal ducts, biliary epithelium, gastrointestinal epithelium, pancreatic duct cells, reproductive epithelium, epidydimal cells, and/or cells of the hepatobiliary tree, e.g., clara cells, e.g., ciliated cells, e.g., goblet cells, e.g., basal cells, e.g., acinus cells, e.g., bronchioalveolar stem cell e.g., lung epithelial cells, e.g., nasal epithelial cells, e.g., tracheal epithelial cells, e.g., bronchial epithelial cells, e.g., enteroendocrine cells, e.g., Brunner's gland cells, e.g., epididymal epithelium, and transplanted into the subject.

In an embodiment, a heterologous stem cell can be treated ex vivo, differentiated into airway epithelium, pulmonary epithelium, submucosal glands, submucosal ducts, biliary epithelium, gastrointestinal epithelium, pancreatic duct cells, reproductive epithelium, epidydimal cells, and/or cells of the hepatobiliary tree, e.g., clara cells, e.g., ciliated cells, e.g., goblet cells, e.g., basal cells, e.g., acinus cells, e.g., bronchioalveolar stem cell e.g., lung epithelial cells, e.g., nasal epithelial cells, e.g., tracheal epithelial cells, e.g., bronchial epithelial cells, e.g., enteroendocrine cells, e.g., Brunner's gland cells, e.g., epididymal epithelium, and transplanted into the subject.

In an embodiment, the method described herein comprises delivery of gRNA or other components described herein, e.g., a Cas9 molecule and a template nucleic acid, by inhalation, e.g., via nebulizer. In an embodiment, the method described herein comprises delivery of gRNA or other components described herein, e.g., a Cas9 molecule and a template nucleic acid by intravenous administration. In an embodiment, the method described herein comprises delivery of gRNA or other components described herein, e.g., a Cas9 molecule and a template nucleic acid by intraparenchymal injection into lung tissue. In an embodiment, the method described herein comprises delivery of gRNA or other components described herein, e.g., a Cas9 molecule and a template nucleic acid, by intraparenchymal, intralveolar, intrabronchial, intratracheal injection into the trachea, bronchial tree and/or alveoli. In an embodiment, the method described herein comprises delivery of gRNA or other components described herein, e.g., a Cas9 molecule and a template nucleic acid, by intravenous, intraparenchymal or other directed injection or administration to any of the following locations: the portal circulation, liver parenchyma, pancreas, pancreatic duct, bile duct, jejunum, ileum, duodenum, stomach, upper intestine, lower intestine, gastrointestinal tract, epididymis, or reproductive tract.

In an embodiment, a gRNA or other components described herein, e.g., a Cas9 molecule and a template nucleic acid are delivered, e.g., to a subject, by AAV, e.g., via nebulizer, or via nasal spray or inhaled, with or without accelerants to aid in absorption. In an embodiment, a gRNA or other components described herein, e.g., a Cas9 molecule and a template nucleic acid are delivered, e.g., to a subject, by Sendai virus, adenovirus, lentivirus or other modified or unmodified viral delivery particle.

In an embodiment, a gRNA or other components described herein, e.g., a Cas9 molecule and a template nucleic acid are delivered, e.g., to a subject, via nebulizer or jet nebulizer, nasal spray, or inhalation. In an embodiment, a gRNA or other components described herein, e.g., a Cas9 molecule and a template nucleic acid, is formulated in an aerosolized cationic liposome, lipid nanoparticle, lipoplex, non-lipid polymer complex or dry powder, e.g., for delivery via nebulizer, with or without accelerants to aid in absorption.

In an embodiment, a gRNA or other components described herein, e.g., a Cas9 molecule and a template nucleic acid are delivered, e.g., to a subject, via liposome GL67A. GL67A is described, e.g., www.cfgenetherapy.org.uk/clinical/product.html; Eastman et al., Hum Gene Ther. 1997 Apr 10; 8(6):765-73.

Disclosed herein are methods for altering the CF target position in the CFTR and/or SCNN1A genes.

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5535.1 Methods and compositions disclosed herein provide a number of approaches for treating or preventing CF and CF-like disease. In an embodiment, methods described herein provide for treating or preventing CF and CF-like disease by correcting a target position in the CFTR gene to provide corrected, or functional, e.g., wild type, CFTR. In an embodiment, methods described herein allow for treating or preventing CF and CF-like disease by inducing or introducing a mutation that reduces the level of functional SCNN1A gene product. In subjects with CF or CF- like disease, these methods can be used alone, e.g. CFTR correction, e.g., SCNN1A knockout or knockdown, or in combination, e.g., CFTR correction with SCNN1A knockout or knockdown.

Several approaches are detailed in the following, including target positions and mutations amenable to approach. In the description below, approaches 1, 2 and 3 (e.g., 3A and 3B) correspond to methods to alter CFTR. In the description below, approach 4 and 6 correspond to methods to alter SCNN1A. One or more of the approaches can be used alone or in combination. For example, approaches 1, 2, and 3 can be used alone or approach 1 can be combined with approach 4, or approach 2 can be combined with approach 4 or approach 3 (e.g., 3 A or 3B) can be combined with approach 4.

Methods to Alter CFTR

In one aspect, methods and compositions discussed herein, provide for the correction of the underlying cause of CF or CF-like disease, e.g., the correction of a mutation at a target position in the CFTR gene.

As disclosed herein, the CFTR gene can be altered by gene editing, e.g., using CRISPR- Cas9 mediated methods as described herein. Methods and compositions discussed herein, provide for altering a CF target position in the CFTR gene. A CF target position can be altered by gene editing, e.g., using CRISPR-Cas9 mediated methods to alter the CFTR gene.

In an embodiment, while some of the disclosure herein is presented in the context of the mutation in the CFTR gene that gives rise to an F508 mutant protein (e.g., F508del mutant protein) or a G551 mutant protein (e.g., G551D mutant protein), or a G542 mutant protein (e.g., G542X mutant protein), or a mutant protein (e.g., mutant protein), or a N1303 mutant protein (e.g., N1303K mutant protein), or a Rl 17 mutant protein (e.g., Rl 17H mutant protein), or a W1282 mutant protein (e.g., W1282X mutant protein), or a R553 mutant protein (e.g., R553X mutant protein), or a c.3717+12191 mutant protein (e.g., c.3717+12191C>T mutant protein), or a

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5535.1 c.2657+5 mutant protein (e.g., c.2657+5G>A mutant protein), or a c.3140-26 mutant protein (e.g., c.3140-26 A>G mutant protein), the methods and compositions herein are broadly applicable to any mutation, e.g., a point mutation or a deletion, in the CFTR gene that gives rise to CF or CF-like disease.

The alteration of the CFTR gene can be mediated by any mechanism. Exemplary mechanisms that can be associated with the alteration of the CFTR gene include, but are not limited to, non-homologous end joining (e.g., classical or alternative), microhomology-mediated end joining (MMEJ), homology-directed repair (e.g., endogenous donor template mediated), SDSA (synthesis dependent strand annealing) or single strand annealing or single strand invasion, all with or without the addition of an endogenous- promoter driven cDNA encoding the CFTR gene.

Approach 1: In an embodiment, one approach to treat or prevent CF or CF-like disease is to repair (i.e., correct) one or more mutations in the CFTR gene, e.g., by HDR. While not wishing to be bound by theory, it is believed that correction of the mutation(s) (e.g., mediated by HDR) restore the mutant CFTR gene to its wild type state. In an embodiment, single stranded oligonucleotides (ssODNs) are used as a donor template. In another embodiment, double stranded DNA donor is used as a donor template. Donor templates contain DNA sequence which, upon incorporation, result in the expression of a functional version of the CFTR protein. In an embodiment, one CFTR allele is repaired in the subject. In another embodiment, both CFTR alleles are repaired in the subject. In one aspect, methods and compositions discussed herein, provide for the correction of the underlying genetic cause of CF or CF-like disease, e.g., the correction of a mutation at a target position in the CFTR gene, e.g., correction of a mutation (e.g., delF508, G551DG542X, N1303K, R117H, W1282X, or R553X) in the CFTR gene.

Mutations in the CFTR gene amenable to the approach described herein include, but are not limited to any of the following mutations, e.g., F508del, G551D, G542X, N1303K, R117H, W1282X, or R553X.

In an embodiment, the homology-directed repair of genomic sequence including the mutation at the CF target position (e.g., F508del, G551D, G542X, N1303K, R117H, W1282X, or R553X) gives rise to alteration of the CFTR gene. This approach leads to the cessation of production of mutant CFTR channel and results in the production of wild-type CFTR channel.

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5535.1 This approach will prevent the development or progression of lung, gastrointestinal and/or reproductive disease in subjects with CFTR mutations.

In an embodiment, the method provides for the correction of a mutation at a target position in the CFTR gene, e.g., correction of a mutation, e.g., an F508del, G551D, G542X, N1303K, Rl 17H, W1282X, or R553X substitution in the CFTR gene. As described herein, in an embodiment, the method comprises the introduction of one or more breaks (e.g., single strand breaks or double strand breaks) sufficiently close to (e.g., either 5' or 3' to) the target position in the CFTR gene, e.g., F508del, G551D, G542X, N1303K, R117H, W1282X, or R553X.

In an embodiment, the targeting domain of the gRNA molecule is configured to provide a cleavage event, e.g., a double strand break or a single strand break, sufficiently close to (e.g., either 5' or 3' to) the target position in the CFTR gene, e.g., F508del, G551D, G542X, N1303K, R117H, W1282X, or R553X to allow correction, e.g., an alteration in the CFTR gene, e.g., an alternation associated with HDR. In an embodiment, the targeting domain is configured such that a cleavage event, e.g., a double strand or single strand break, is positioned within 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450 or 500 nucleotides of the target position in the CFTR gene, e.g., F508del, G551D, G542X, N1303K, Rl 17H, W1282X, or R553X. The break, e.g., a double strand or single strand break, can be positioned upstream or downstream of the target position in the CFTR gene, e.g., F508del, G551D, G542X, N1303K, R117H, W1282X, or R553X.

In an embodiment, a second, third and/or fourth gRNA molecule is configured to provide a cleavage event, e.g., a double strand break or a single strand break, sufficiently close to (e.g., either 5' or 3' to) the target position in the CFTR gene, e.g., F508del, G551D, G542X, N1303K, Rl 17H, W1282X, or R553X to allow correction, e.g., an alteration associated with HDR in the CFTR gene. In an embodiment, the targeting domain is configured such that a cleavage event, e.g., a double strand or single strand break, is positioned within 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450 or 500 nucleotides of the target position in the CFTR gene, e.g., F508del, G551D, G542X, N1303K, R117H, W1282X, or R553X. The break, e.g., a double strand or single strand break, can be positioned upstream or downstream of the target position in the CFTR gene, e.g., F508del, G551D, G542X, N1303K, Rl 17H, W1282X, or R553X.

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5535.1 In an embodiment, a single strand break is accompanied by an additional single strand break, positioned by a second, third and/or fourth gRNA molecule, as discussed below. For example, The targeting domains bind configured such that a cleavage event, e.g., the two single strand breaks, are positioned within 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450 or 500 nucleotides of the target position in the CFTR gene, e.g., F508del, G551D, G542X, N1303K, R117H, W1282X, or R553X. In an embodiment, the first and second gRNA molecules are configured such, that when guiding a Cas9 nickase, a single strand break will be accompanied by an additional single strand break, positioned by a second gRNA, sufficiently close to one another to result in an alteration of the target position in the CFTR gene, e.g., F508del, G551D, G542X, N1303K, R117H, W1282X, or R553X. In an embodiment, the first and second gRNA molecules are configured such that a single strand break positioned by said second gRNA is within 10, 20, 30, 40, or 50 nucleotides of the break positioned by said first gRNA molecule, e.g., when the Cas9 is a nickase. In an embodiment, the two gRNA molecules are configured to position cuts at the same position, or within a few nucleotides of one another, on different strands, e.g., essentially mimicking a double strand break.

In an embodiment, a double strand break can be accompanied by an additional double strand break, positioned by a second, third and/or fourth gRNA molecule, as is discussed below. For example, the targeting domain of a first gRNA molecule is configured such that a double strand break is positioned upstream of the target position in the CFTR gene, e.g., F508del,

G551D, G542X, N1303K, R117H, W1282X, or R553X, e.g., within 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450 or 500 nucleotides of the target position; and the targeting domain of a second gRNA molecule is configured such that a double strand break is positioned downstream the target position in the CFTR gene, e.g., F508del, G551D, G542X, N1303K, R117H, W1282X, or R553X, e.g., within 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450 or 500 nucleotides of the target position.

In an embodiment, a double strand break can be accompanied by two additional single strand breaks, positioned by a second gRNA molecule and a third gRNA molecule. For example, the targeting domain of a first gRNA molecule is configured such that a double strand break is positioned upstream of the target position in the CFTR gene, e.g., F508del, G551D,

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5535.1 G542X, N1303K, R117H, W1282X, or R553X, e.g., within 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450 or 500 nucleotides of the target position; and the targeting domains of a second and third gRNA molecule are configured such that two single strand breaks are positioned downstream of the target position in the CFTR gene, e.g., F508del, G551D, G542X, N1303K, R117H, W1282X, or R553X, e.g., within 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450 or 500 nucleotides of the target position. In an embodiment, the targeting domain of the first, second and third gRNA molecules are configured such that a cleavage event, e.g., a double strand or single strand break, is positioned, independently for each of the gRNA molecules.

In an embodiment, a first and second single strand breaks can be accompanied by two additional single strand breaks positioned by a third gRNA molecule and a fourth gRNA molecule. For example, the targeting domain of a first and second gRNA molecule are configured such that two single strand breaks are positioned upstream of the target position in the CFTR gene, e.g., F508del, G551D, G542X, N1303K, R117H, W1282X, or R553X, e.g., within 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450 or 500 nucleotides of the target position in the CFTR gene, e.g., F508del, G551D, G542X, N1303K, Rl 17H, W1282X, or R553X; and the targeting domains of a third and fourth gRNA molecule are configured such that two single strand breaks are positioned downstream of the target position in the CFTR gene, e.g., F508del, G551D, G542X, N1303K, R117H, W1282X, or R553X, e.g., within 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450 or 500 nucleotides of the target position in the CFTR gene, e.g., F508del, G551D, G542X, N1303K, R117H, W1282X, or R553X.

In an embodiment, a single strand break is introduced (e.g., positioned by one gRNA molecule) at or in close proximity to a CF target position in the CFTR gene. In an embodiment, a single gRNA molecule (e.g., with a Cas9 nickase) is used to create a single strand break at or in close proximity to the CF target position, e.g., the gRNA is configured such that the single strand break is positioned either upstream (e.g., within 200 bp upstream) or downstream (e.g., within 200 bp downstream) of the CF target position. In an embodiment, the break is positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, a double strand break is introduced (e.g., positioned by one gRNA molecule) at or in close proximity to a CF target position in the CFTR gene. In an embodiment,

61

5535.1 a single gRNA molecule (e.g., with a Cas9 nuclease other than a Cas9 nickase) is used to create a double strand break at or in close proximity to the CF target position, e.g., the gRNA molecule is configured such that the double strand break is positioned either upstream (e.g., within 200 bp upstream) or downstream of (e.g., within 200 bp downstream) of a CF target position. In an embodiment, the break is positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, two single strand breaks are introduced (e.g., positioned by two gRNA molecules) at or in close proximity to a CF target position in the CFTR gene. In an embodiment, two gRNA molecules (e.g., with one or two Cas9 nickcases) are used to create two single strand breaks at or in close proximity to the CF target position, e.g., the gRNAs molecules are configured such that both of the single strand breaks are positioned upstream (e.g., within 200 bp upstream) or downstream (e.g., within 200 bp downstream) of the CF target position. In another embodiment, two gRNA molecules (e.g., with two Cas9 nickcases) are used to create two single strand breaks at or in close proximity to the CF target position, e.g., the gRNAs molecules are configured such that one single strand break is positioned upstream (e.g., within 200 bp upstream) and a second single strand break is positioned downstream (e.g., within 200 bp downstream) of the CF target position. In an embodiment, the breaks are positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, two double strand breaks are introduced (e.g., positioned by two gRNA molecules) at or in close proximity to a CF target position in the CFTR gene. In an embodiment, two gRNA molecules (e.g., with one or two Cas9 nucleases that are not Cas9 nickases) are used to create two double strand breaks to flank a CF target position, e.g., the gRNA molecules are configured such that one double strand break is positioned upstream (e.g., within 200 bp upstream) and a second double strand break is positioned downstream (e.g., within 200 bp downstream) of the CF target position. In an embodiment, the breaks are positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, one double strand break and two single strand breaks are introduced (e.g., positioned by three gRNA molecules) at or in close proximity to a CF target position in the CFTR gene. In an embodiment, three gRNA molecules (e.g., with a Cas9 nuclease other than a Cas9 nickase and one or two Cas9 nickases) to create one double strand break and two single strand breaks to flank an CF target position, e.g., the gRNA molecules are configured such that

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5535.1 the double strand break is positioned upstream or downstream of (e.g., within 200 bp upstream or downstream) of the CF target position, and the two single strand breaks are positioned at the opposite site, e.g., downstream or upstream (within 200 bp downstream or upstream), of the CF target position. In an embodiment, the breaks are positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, four single strand breaks are introduced (e.g., positioned by four gRNA molecules) at or in close proximity to a CF target position in the CFTR gene. In an embodiment, four gRNA molecule (e.g., with one or more Cas9 nickases are used to create four single strand breaks to flank an CF target position in the CFTR gene, e.g., the gRNA molecules are configured such that a first and second single strand breaks are positioned upstream (e.g., within 200 bp upstream) of the CF target position, and a third and a fourth single stranded breaks are positioned downstream (e.g., within 200 bp downstream) of the CF target position. In an embodiment, the breaks are positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, two or more (e.g., three or four) gRNA molecules are used with one

Cas9 molecule. In another embodiment, when two or more (e.g., three or four) gRNAs are used with two or more Cas9 molecules, at least one Cas9 molecule is from a different species than the other Cas9 molecule(s). For example, when two gRNA molecules are used with two Cas9 molecules, one Cas9 molecule can be from one species and the other Cas9 molecule can be from a different species. Both Cas9 species are used to generate a single or double-strand break, as desired.

Approach 2: HDR-mediated knockin of cDNA to alter the CFTR gene. In an

embodiment, a CF target knockin position is altered. Altering the CF target knockin position refers to homology-directed knockin of genomic sequence, including the delivery of cDNA template of contiguous exons (X+1) through exon 27 of CFTR gene, wherein exon X is any exon between exon 1 and exon 27. Targeted knockin of CFTR cDNA leads to the cessation of production of mutant or truncated CFTR protein and results in the production of functional CFTR protein. In an embodiment, a donor template is provided to mediate HDR-mediated knockin. In an embodiment, said donor template comprise homology arms, splice acceptor, contiguous coding sequence of exons (X+1) through exon 27 of CFTR gene and polyadenylation

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5535.1 signal. While not wishing to be bound by theory, it is believed that correction of the mutation(s) (e.g., mediated by HDR) retore the mutant CFTR gene to its wild type state. In another embodiment, double stranded DNA donor is used as a donor template. Donor templates contain DNA sequence which, upon incorporation, would result in the expression of a functional version of the CFTR protein. In an embodiment, one CFTR allele is repaired in the subject. In another embodiment, both CFTR alleles are repaired in the subject. In one aspect, methods and compositions discussed herein, provide for the correction of the underlying genetic cause of CF or CF-like disease, e.g., the correction of a mutation at a CF target position in the CFTR gene, e.g., correction of a mutation. This approach leads to the cessation of production of mutant or truncated CFTR protein and results in the production of functional CFTR protein. This approach prevents the development or progression of lung, gastrointestinal and/or reproductive disease in a subject due to the cessation of production of mutant CFTR protein and restoration of functional CFTR protein production. This approach cures and/or prevents the progression of lung, gastrointestinal and/or reproductive disease in any subject with CF or CF-like disease deficiency who has a mutation in exon (X+l) through exon 27 of the CFTR gene, or in any subject who has a mutation in an intronic or exonic region of the CFTR gene that is after exon X.

In an embodiment, homology-directed repair of the CFTR gene in any subjects with CF mutations in exons 3 through 27 and introns 2 through 26 by targeting intronic region between exons 2 and 3 and with delivery of a homology-directed repair template including homology arms, splice acceptor, coding sequence of contiguous exons 3-27 of CFTR gene and

polyadenylation signal.

In an embodiment, the CF target position is the intronic region between exons 2 and 3. Altering the CF target position refers to homology-directed repair of genomic sequence including the delivery of cDNA template of exons 3-27 of CFTR gene. This approach cures and/or prevents the progression of lung, gastrointestinal and/or reproductive disease in any subject with CF or CF-like disease deficiency who has a mutation in exons 3-27 of the CFTR gene, or in any subject who has a mutation in an intronic or exonic region of the CFTR gene that is on or after the second intron, including but not limited to the following mutations: e.g., F508del,

G551D,G542X, N1303K, R117H, W1282X, R553X, c.3717+12191C>T, 2657+5G>A, or c.3140-26A>G.

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5535.1 In an embodiment, the CF target position is the intronic region between exons 10 and 11. Altering the CF target position refers to homology-directed repair of genomic sequence including the delivery of cDNA template of exons 11-27 of CFTR gene. This approach cures and/or prevents the progression of lung, gastrointestinal and/or reproductive disease in any subject with CF or CF-like disease deficiency who has a mutation in exons 11-27 of the CFTR gene, or in any subject who has a mutation in an intronic or exonic region of the CFTR gene that is on or after the second intron, including but not limited to the following mutations: e.g., F508del.

In an embodiment, the method provides for the correction of a mutation at a target position in the CFTR gene, e.g., F508del, G551D,G542X, N1303K, R117H, W1282X, R553X, c.3717+12191C>T, 2657+5G>A, or c.3140-26A>G. As described herein, in one embodiment, the method comprises the introduction of one or more breaks (e.g., single strand breaks or double strand breaks) sufficiently close to (e.g., either 5' or 3' to) the target position in the CFTR gene, e.g., intron 2 or intron 10.

In an embodiment, the targeting domain of the gRNA molecule is configured to provide a cleavage event, e.g., a double strand break or a single strand break, sufficiently close to (e.g., either 5' or 3' to) the target position e.g., intron 2 or intron 10 allow correction, e.g., an alteration in the CFTR gene, e.g., an alternation associated with HDR. In an embodiment, the targeting domain is configured such that a cleavage event, e.g., a double strand or single strand break, is positioned within 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, or 200 nucleotides of the target position in the CFTR gene, e.g., intron 2 or intron 10. The break, e.g., a double strand or single strand break, can be positioned upstream or downstream of the target position in the CFTR gene, e.g., intron 2 or intron 10.

In an embodiment, a second, third and/or fourth gRNA molecule is configured to provide a cleavage event, e.g., a double strand break or a single strand break, sufficiently close to (e.g., either 5' or 3' to) the target position e.g., intron 2 or intron 10 to allow correction, e.g., an alteration associated with HDR in the CFTR gene. In an embodiment, the targeting domain is configured such that a cleavage event, e.g., a double strand or single strand break, is positioned within 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, or 200 nucleotides of the target position in the CFTR gene, e.g., intron 2 or intron 10. The break, e.g., a double strand or single strand break, can be positioned upstream or downstream of the target position in the CFTR gene, e.g., intron 2 or intron 10.

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5535.1 In an embodiment, a single strand break is accompanied by an additional single strand break, positioned by a second, third and/or fourth gRNA molecule, as discussed below. For example, The targeting domains bind configured such that a cleavage event, e.g., the two single strand breaks, are positioned within 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, or 200 nucleotides of the target position in the CFTR gene, e.g., intron 2 or intron 10. In an embodiment, the first and second gRNA molecules are configured such, that when guiding a Cas9 nickase, a single strand break will be accompanied by an additional single strand break, positioned by a second gRNA, sufficiently close to one another to result in an alteration of the target position in the CFTR gene, e.g., intron 2 or intron 10. In an embodiment, the first and second gRNA molecules are configured such that a single strand break positioned by said second gRNA is within 10, 20, 30, 40, or 50 nucleotides of the break positioned by said first gRNA molecule, e.g., when the Cas9 is a nickase. In an embodiment, the two gRNA molecules are configured to position cuts at the same position, or within a few nucleotides of one another, on different strands, e.g., essentially mimicking a double strand break.

In an embodiment, a double strand break can be accompanied by an additional double strand break, positioned by a second, third and/or fourth gRNA molecule, as is discussed below. For example, the targeting domain of a first gRNA molecule is configured such that a double strand break is positioned upstream of the target position in the CFTR gene, e.g., intron 2 or intron 10, e.g., within 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, or 200 nucleotides of the target position; and the targeting domain of a second gRNA molecule is configured such that a double strand break is positioned downstream the target position in the CFTR gene, e.g., intron 2 or intron 10, e.g., within 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, or 200 nucleotides of the target position.

In an embodiment, a double strand break can be accompanied by two additional single strand breaks, positioned by a second gRNA molecule and a third gRNA molecule. For example, the targeting domain of a first gRNA molecule is configured such that a double strand break is positioned upstream of the target position in the CFTR gene, e.g., intron 2 or intron 10 e.g., within 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, or 200 nucleotides of the target position; and the targeting domains of a second and third gRNA molecule are configured such that two single strand breaks are positioned downstream of the target position in the CFTR gene, e.g., intron 2 or intron 10, e.g., within 1, 2, 3, 4, 5, 10, 15, 20,

66

5535.1 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, or 200 nucleotides of the target position. In an embodiment, the targeting domain of the first, second and third gRNA molecules are configured such that a cleavage event, e.g., a double strand or single strand break, is positioned,

independently for each of the gRNA molecules.

In an embodiment, a first and second single strand breaks can be accompanied by two additional single strand breaks positioned by a third gRNA molecule and a fourth gRNA molecule. For example, the targeting domain of a first and second gRNA molecule are configured such that two single strand breaks are positioned upstream of the target position in the CFTR gene, e.g., intron 2 or intron 10, e.g., within 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, or 200 nucleotides of the target position in the CFTR gene, e.g., intron 2 or intron 10; and the targeting domains of a third and fourth gRNA molecule are configured such that two single strand breaks are positioned downstream of the target position in the CFTR gene, e.g., intron 2 or intron 10, e.g., within 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, or 200 nucleotides of the target position in the CFTR gene, e.g., intron 2 or intron 10.

In an embodiment, a single strand break is introduced (e.g., positioned by one gRNA molecule) at or in close proximity to a CF target position in the CFTR gene. In an embodiment, a single gRNA molecule (e.g., with a Cas9 nickase) is used to create a single strand break at or in close proximity to the CF target position, e.g., the gRNA is configured such that the single strand break is positioned either upstream (e.g., within 200 bp upstream) or downstream (e.g., within 200 bp downstream) of the CF target position. In an embodiment, the break is positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, a double strand break is introduced (e.g., positioned by one gRNA molecule) at or in close proximity to a CF target position in the CFTR gene. In an embodiment, a single gRNA molecule (e.g., with a Cas9 nuclease other than a Cas9 nickase) is used to create a double strand break at or in close proximity to the CF target position, e.g., the gRNA molecule is configured such that the double strand break is positioned either upstream (e.g., within 200 bp upstream) or downstream of (e.g., within 200 bp downstream) of a CF target position. In an embodiment, the break is positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

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5535.1 In an embodiment, two single strand breaks are introduced (e.g., positioned by two gRNA molecules) at or in close proximity to a CF target position in the CFTR gene. In an embodiment, two gRNA molecules (e.g., with one or two Cas9 nickcases) are used to create two single strand breaks at or in close proximity to the CF target position, e.g., the gRNAs molecules are configured such that both of the single strand breaks are positioned upstream (e.g., within 200 bp upstream) or downstream (e.g., within 200 bp downstream) of the CF target position. In another embodiment, two gRNA molecules (e.g., with two Cas9 nickcases) are used to create two single strand breaks at or in close proximity to the CF target position, e.g., the gRNAs molecules are configured such that one single strand break is positioned upstream (e.g., within 200 bp upstream) and a second single strand break is positioned downstream (e.g., within 200 bp downstream) of the CF target position. In an embodiment, the breaks are positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, two double strand breaks are introduced (e.g., positioned by two gRNA molecules) at or in close proximity to a CF target position in the CFTR gene. In an embodiment, two gRNA molecules (e.g., with one or two Cas9 nucleases that are not Cas9 nickases) are used to create two double strand breaks to flank a CF target position, e.g., the gRNA molecules are configured such that one double strand break is positioned upstream (e.g., within 200 bp upstream) and a second double strand break is positioned downstream (e.g., within 200 bp downstream) of the CF target position. In an embodiment, the breaks are positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, one double strand break and two single strand breaks are introduced (e.g., positioned by three gRNA molecules) at or in close proximity to a CF target position in the CFTR gene. In an embodiment, three gRNA molecules (e.g., with a Cas9 nuclease other than a Cas9 nickase and one or two Cas9 nickases) to create one double strand break and two single strand breaks to flank an CF target position, e.g., the gRNA molecules are configured such that the double strand break is positioned upstream or downstream of (e.g., within 200 bp upstream or downstream) of the CF target position, and the two single strand breaks are positioned at the opposite site, e.g., downstream or upstream (within 200 bp downstream or upstream), of the CF target position. In an embodiment, the breaks are positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

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5535.1 In an embodiment, four single strand breaks are introduced (e.g., positioned by four gRNA molecules) at or in close proximity to a CF target position in the CFTR gene. In an embodiment, four gRNA molecule (e.g., with one or more Cas9 nickases are used to create four single strand breaks to flank an CF target position in the CFTR gene, e.g., the gRNA molecules are configured such that a first and second single strand breaks are positioned upstream (e.g., within 200 bp upstream) of the CF target position, and a third and a fourth single stranded breaks are positioned downstream (e.g., within 200 bp downstream) of the CF target position. In an embodiment, the breaks are positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, two or more (e.g., three or four) gRNA molecules are used with one

Cas9 molecule. In another embodiment, when two or more (e.g., three or four) gRNAs are used with two or more Cas9 molecules, at least one Cas9 molecule is from a different species than the other Cas9 molecule(s). For example, when two gRNA molecules are used with two Cas9 molecules, one Cas9 molecule can be from one species and the other Cas9 molecule can be from a different species. Both Cas9 species are used to generate a single or double-strand break, as desired.

Approach 3A: In an embodiment, Cas9-mediated removal and/or disruption of an intronic segment of DNA, within a CFTR intron, to restore post-transcriptional processing accuracy, e.g., without the use of homology-directed repair. CFTR mutations (e.g.,

c.3717+12191C>T, e.g., 2657+5G>A, e.g., c.3140-26A>G) can cause abbarent post- transcriptional processing, such as missplicing by the creation of novel splice sites which can lead to the early truncation of non-functional CFTR protein resulting in aberrant CFTR channel formation. In one aspect, methods and compositions discussed herein, provide for altering the CF target position in the CFTR gene. The CF target position (e.g. c.3717+12191, also known as c.3849+10kb, e.g., c.2657+5, also known as c.2789+5, e.g., C.3140-26A, also known as c.3272- 26) can be altered, e.g., by non-homologous end-joining mediated removal and/or disruption of a splice site mutation. In the case of a subject with a 3717+12191C>T mutation, the CF target position is 500bp upstream and/or downstream of c.3717+12191 within intron 22. In the case of a subject with a c.2657+5G>A mutation, the CF target position is 200bp upstream within exon 16, and intron 16 and intron 15 and/or downstream of c.2657+5 within intron 16. In the case of a

69

5535.1 subject with a c.3140-26A>G mutation, the CF target position is 200bp upstream and/or downstream of c.3140-26 within intron 19 and exon 20. The removal, disruption and/or repair of a splice site mutation will restore accurate splicing and cease production of aberrant truncation of CFTR protein. This approach will lead to the cessation of production of truncatednon-functional CFTR channel and will lead to the production of wild-type CFTR channel. This approach will prevent the development or progression of lung, gastrointestinal and/or reproductive disease in subjects with CFTR mutations.

In an embodiment, methods and compositions discussed herein, provide for altering the CF target position in the CFTR gene. The alteration can be achieved by (1) break- induced introduction of an indel (also referred to herein as NHEJ-mediated introduction of an indel) in close proximity to or including a CF target position (e.g., c.3717+12191C>T, 2657+5G>A, or c.3140-26A>G), or (2) break-induced deletion (also referred to herein as NHEJ-mediated deletion) of genomic sequence including the mutation at a CF target position (e.g.,

c.3717+12191C>T, 2657+5G>A, or c.3140-26A>G). Both approaches give rise to the loss or destruction of the abbarent post- transcriptional processing.

In an embodiment, the method comprises introducing a break-induced indel in close proximity to or including the CF target position (e.g., c.3717+12191C>T, 2657+5G>A, or c.3140-26A>G). As described herein, in one embodiment, the method comprises the

introduction of a double strand break sufficiently close to (e.g., either 5' or 3' to) the CF target position (e.g., c.3717+12191C>T, 2657+5G>A, or c.3140-26A>G), such that the break-induced indel could be reasonably expected to span the mutation. A single gRNAs, e.g., unimolecular (or chimeric) or modular gRNA molecules, is configured to position a double strand break sufficiently close to the CF target position in the CFTR gene. The double strand break may be positioned within 500 nucleotides (e.g., within 1, 2, 3, 4, 5, 10, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 100, 200, 300, 400 or 500 nucleotides) upstream of the CF target poistion, or within 500 nucleotides (e.g., within 1, 2, 3, 4, 5, 10, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 100, 200, 300, 400 or 500 nucleotides) downstream of the CF target position. While not wishing to be bound by theory, in an embodiment, it is believed that NHEJ-mediated repair of the double strand break allows for the NHEJ-mediated introduction of an indel in close proximity to or including the CF target position.

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5535.1 In another embodiment, the method comprises the introduction of a pair of single strand breaks sufficiently close to (either 5' or 3' to, respectively) the mutation at the CF target position (e.g., c.3717+12191C>T, 2657+5G>A, or c.3140-26A>G), such that the break-induced indel could be reasonably expected to span the mutation. Two gRNAs, e.g., unimolecular (or chimeric) or modular gRNA molecules, are configured to position the two single strand breaks sufficiently close to the CF target position in the CFTR gene. In an embodiment, the pair of single strand breaks is positioned within 500 nucleotides (e.g., within 1, 2, 3, 4, 5, 10, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 100, 200, 300, 400 or 500 nucleotides) upstream of the CF target position, or within 500 nucleotides (e.g., within 1, 2, 3, 4, 5, 10, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 100, 200, 300, 400 or 500 nucleotides) downstream of the CF target position. While not wishing to be bound by theory, in an embodiment, it is believed that NHEJ mediated repair of the pair of single strand breaks allows for the NHEJ-mediated introduction of an indel in close proximity to or including the CF target position. In an embodiment, the pair of single strand breaks may be accompanied by an additional double strand break, positioned by a third gRNA molecule, as is discussed below. In another embodiment, the pair of single strand breaks may be accompanied by two additional single strand breaks positioned by a third gRNA molecule and a fourth gRNA molecule, as is discussed below.

In another embodiment, the method comprises the introduction of two sets of breaks (e.g., a pair of double strand breaks targeted by two gRNAs) sufficiently close to (either 5' or 3' to, respectively) the mutation at the CF target position (e.g., c.3717+12191C>T, 2657+5G>A, or c.3140-26A>G). such that the break-induced indel could be reasonably expected to span the mutation. Two gRNAs, e.g., unimolecular (or chimeric) or modular gRNA molecules, are configured to position the two sets of breaks (e.g., a pair of double strand breaks) sufficiently close to the CF target position in the CFTR gene. In an embodiment, the pair of single strand breaks is positioned within 500 nucleotides (e.g., within 1, 2, 3, 4, 5, 10, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 100, 200, 300, 400 or 500 nucleotides) upstream of the CF target position, or within 500 nucleotides (e.g., within 1, 2, 3, 4, 5, 10, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 100, 200, 300, 400 or 500 nucleotides) downstream of the CF target position. While not wishing to be bound by theory, in an embodiment, it is believed that NHEJ mediated repair of two sets of breaks (e.g., a pair of double strand breaks) allows for the NHEJ-mediated introduction of an indel in close proximity to or including the CF target position.

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5535.1 In another embodiment, the method comprises the introduction of two sets of breaks (e.g., one double strand break and a pair of single strand breaks targeted by three gRNAs) sufficiently close to (either 5' or 3' to, respectively) the mutation at the CF target position (e.g., c.3717+12191C>T, 2657+5G>A, or c.3140-26A>G). such that the break-induced indel could be reasonably expected to span the mutation. Two gRNAs, e.g., unimolecular (or chimeric) or modular gRNA molecules, are configured to position the two sets of breaks (e.g., one double strand break and a pair of single strand breaks) sufficiently close to the CF target position in the CFTR gene. In an embodiment, the pair of single strand breaks is positioned within 500 nucleotides (e.g., within 1, 2, 3, 4, 5, 10, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 100, 200, 300, 400 or 500 nucleotides) upstream of the CF target position, or within 500 nucleotides (e.g., within 1, 2, 3, 4, 5, 10, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 100, 200, 300, 400 or 500 nucleotides) downstream of the CF target position. While not wishing to be bound by theory, in an

embodiment, it is believed that NHEJ mediated repair of two sets of breaks (e.g., one double strand break and a pair of single strand breaks) allows for the NHEJ-mediated introduction of an indel in close proximity to or including the CF target position.

In another embodiment, the method comprises the introduction of two sets of breaks (e.g., two pairs of single strand breaks targeted by four gRNAs) sufficiently close to (either 5' or 3' to, respectively) the mutation at the CF target position (e.g., c.3717+12191C>T, 2657+5G>A, or c.3140-26A>G). such that the break-induced indel could be reasonably expected to span the mutation. Two gRNAs, e.g., unimolecular (or chimeric) or modular gRNA molecules, are configured to position the two sets of breaks (e.g., two pairs of single strand breaks s)

sufficiently close to the CF target position in the CFTR gene. In an embodiment, the pair of single strand breaks is positioned within 500 nucleotides (e.g., within 1, 2, 3, 4, 5, 10, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 100, 200, 300, 400 or 500 nucleotides) upstream of the CF target position, or within 500 nucleotides (e.g., within 1, 2, 3, 4, 5, 10, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 100, 200, 300, 400 or 500 nucleotides) downstream of the CF target position. While not wishing to be bound by theory, in an embodiment, it is believed that NHEJ mediated repair of two sets of breaks (e.g., two pairs of single strand breaks) allows for the NHEJ-mediated introduction of an indel in close proximity to or including the CF target position.

In an embodiment, a single strand break is introduced (e.g., positioned by one gRNA molecule) at or in close proximity to a CF target position in the CFTR gene. In an embodiment,

72

5535.1 a single gRNA molecule (e.g., with a Cas9 nickase) is used to create a single strand break at or in close proximity to the CF target position, e.g., the gRNA is configured such that the single strand break is positioned either upstream (e.g., within 500 bp, e.g., within 200 bp upstream) or downstream (e.g., within 500 bp, e.g., within 200 bp downstream) of the CF target position. In an embodiment, the break is positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, a double strand break is introduced (e.g., positioned by one gRNA molecule) at or in close proximity to a CF target position in the CFTR gene. In an embodiment, a single gRNA molecule (e.g., with a Cas9 nuclease other than a Cas9 nickase) is used to create a double strand break at or in close proximity to the CF target position, e.g., the gRNA molecule is configured such that the double strand break is positioned either upstream (e.g., within 500 bp, e.g., within 200 bp upstream) or downstream of (e.g., within 500 bp, e.g., within 200 bp downstream) of a CF target position. In an embodiment, the break is positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, two single strand breaks are introduced (e.g., positioned by two gRNA molecules) at or in close proximity to a CF target position in the CFTR gene. In an embodiment, two gRNA molecules (e.g., with one or two Cas9 nickcases) are used to create two single strand breaks at or in close proximity to the CF target position, e.g., the gRNAs molecules are configured such that both of the single strand breaks are positioned upstream (e.g., within 500 bp, e.g., within 200 bp upstream) or downstream (e.g., within 500 bp, e.g., within 200 bp downstream) of the CF target position. In another embodiment, two gRNA molecules (e.g., with two Cas9 nickcases) are used to create two single strand breaks at or in close proximity to the CF target position, e.g., the gRNAs molecules are configured such that one single strand break is positioned upstream (e.g., within 500 bp, e.g., within 200 bp upstream) and a second single strand break is positioned downstream (e.g., within 500 bp, e.g., within 200 bp downstream) of the CF target position. In an embodiment, the breaks are positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, two double strand breaks are introduced (e.g., positioned by two gRNA molecules) at or in close proximity to a CF target position in the CFTR gene. In an embodiment, two gRNA molecules (e.g., with one or two Cas9 nucleases that are not Cas9 nickases) are used to create two double strand breaks to flank a CF target position, e.g., the

73

5535.1 gRNA molecules are configured such that one double strand break is positioned upstream (e.g., within 500 bp, e.g., within 200 bp upstream) and a second double strand break is positioned downstream (e.g., within 500 bp, e.g., within 200 bp downstream) of the CF target position. In an embodiment, the breaks are positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, one double strand break and two single strand breaks are introduced (e.g., positioned by three gRNA molecules) at or in close proximity to a CF target position in the CFTR gene. In an embodiment, three gRNA molecules (e.g., with a Cas9 nuclease other than a Cas9 nickase and one or two Cas9 nickases) to create one double strand break and two single strand breaks to flank an CF target position, e.g., the gRNA molecules are configured such that the double strand break is positioned upstream or downstream of (e.g., within 500 bp, e.g., within 200 bp upstream or downstream) of the CF target position, and the two single strand breaks are positioned at the opposite site, e.g., downstream or upstream (within 200 bp downstream or upstream), of the CF target position. In an embodiment, the breaks are positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, four single strand breaks are introduced (e.g., positioned by four gRNA molecules) at or in close proximity to a CF target position in the CFTR gene. In an embodiment, four gRNA molecule (e.g., with one or more Cas9 nickases are used to create four single strand breaks to flank an CF target position in the CFTR gene, e.g., the gRNA molecules are configured such that a first and second single strand breaks are positioned upstream (e.g., within 500 bp, e.g., within 200 bp upstream) of the CF target position, and a third and a fourth single stranded breaks are positioned downstream (e.g., within 500 bp, e.g., within 200 bp downstream) of the CF target position. In an embodiment, the breaks are positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, two or more (e.g., three or four) gRNA molecules are used with one

Cas9 molecule. In another embodiment, when two or more (e.g., three or four) gRNAs are used with two or more Cas9 molecules, at least one Cas9 molecule is from a different species than the other Cas9 molecule(s). For example, when two gRNA molecules are used with two Cas9 molecules, one Cas9 molecule can be from one species and the other Cas9 molecule can be from a different species. Both Cas9 species are used to generate a single or double-strand break, as desired.

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5535.1 In an embodiment, a single strand break is introduced (e.g., positioned by one gRNA molecule) at or in close proximity to a CF target position in the CFTR gene. In an embodiment, a single gRNA molecule (e.g., with a Cas9 nickase) is used to create a single strand break at or in close proximity to the CF target position, e.g., the gRNA is configured such that the single strand break is positioned either upstream (e.g., within 500 bp upstream) or downstream (e.g., within 500 bp downstream) of the CF target position. In an embodiment, the break is positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, a double strand break is introduced (e.g., positioned by one gRNA molecule) at or in close proximity to a CF target position in the CFTR gene. In an embodiment, a single gRNA molecule (e.g., with a Cas9 nuclease other than a Cas9 nickase) is used to create a double strand break at or in close proximity to the CF target position, e.g., the gRNA molecule is configured such that the double strand break is positioned either upstream (e.g., within 500 bp upstream) or downstream of (e.g., within 500 bp downstream) of a CF target position. In an embodiment, the break is positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, two single strand breaks are introduced (e.g., positioned by two gRNA molecules) at or in close proximity to a CF target position in the CFTR gene. In an embodiment, two gRNA molecules (e.g., with one or two Cas9 nickcases) are used to create two single strand breaks at or in close proximity to the CF target position, e.g., the gRNAs molecules are configured such that both of the single strand breaks are positioned upstream (e.g., within 500 bp upstream) or downstream (e.g., within 500 bp downstream) of the CF target position. In another embodiment, two gRNA molecules (e.g., with two Cas9 nickcases) are used to create two single strand breaks at or in close proximity to the CF target position, e.g., the gRNAs molecules are configured such that one single strand break is positioned upstream (e.g., within 500 bp upstream) and a second single strand break is positioned downstream (e.g., within 500 bp downstream) of the CF target position. In an embodiment, the breaks are positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, two double strand breaks are introduced (e.g., positioned by two gRNA molecules) at or in close proximity to a CF target position in the CFTR gene. In an embodiment, two gRNA molecules (e.g., with one or two Cas9 nucleases that are not Cas9 nickases) are used to create two double strand breaks to flank a CF target position, e.g., the

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5535.1 gRNA molecules are configured such that one double strand break is positioned upstream (e.g., within 500 bp upstream) and a second double strand break is positioned downstream (e.g., within 500 bp downstream) of the CF target position. In an embodiment, the breaks are positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, one double strand break and two single strand breaks are introduced

(e.g., positioned by three gRNA molecules) at or in close proximity to a CF target position in the CFTR gene. In an embodiment, three gRNA molecules (e.g., with a Cas9 nuclease other than a Cas9 nickase and one or two Cas9 nickases) to create one double strand break and two single strand breaks to flank an CF target position, e.g., the gRNA molecules are configured such that the double strand break is positioned upstream or downstream of (e.g., within 500 bp upstream or downstream) of the CF target position, and the two single strand breaks are positioned at the opposite site, e.g., downstream or upstream (within 500 bp downstream or upstream), of the CF target position. In an embodiment, the breaks are positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, four single strand breaks are introduced (e.g., positioned by four gRNA molecules) at or in close proximity to a CF target position in the CFTR gene. In an embodiment, four gRNA molecule (e.g., with one or more Cas9 nickases are used to create four single strand breaks to flank an CF target position in the CFTR gene, e.g., the gRNA molecules are configured such that a first and second single strand breaks are positioned upstream (e.g., within 500 bp upstream) of the CF target position, and a third and a fourth single stranded breaks are positioned downstream (e.g., within 500 bp downstream) of the CF target position. In an embodiment, the breaks are positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, two or more (e.g., three or four) gRNA molecules are used with one Cas9 molecule. In another embodiment, when two or more (e.g., three or four) gRNAs are used with two or more Cas9 molecules, at least one Cas9 molecule is from a different species than the other Cas9 molecule(s). For example, when two gRNA molecules are used with two Cas9 molecules, one Cas9 molecule can be from one species and the other Cas9 molecule can be from a different species. Both Cas9 species are used to generate a single or double-strand break, as desired.

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5535.1 Approach 3B: In an embodiment, Cas9-mediated removal and/or disruption of an intronic segment of DNA, within a CFTR intron, to restore post-transcriptional processing accuracy, e.g., with the use of homology-directed repair. CFTR mutations e.g., c.2657+5 (also known as c.2789+5), or C.3140-26A (also known as c.3272-26) can cause abbarent post- transcriptional processing, such as missplicing by the creation of novel splice sites which can lead to production of non-functional CFTR protein resulting in aberrant CFTR channel formation. In one aspect, methods and compositions discussed herein, provide for altering the CF target position in the CFTR gene. The CF target position (e.g., c.2657+5, e.g., C.3140-26A) can be altered by non-homologous end-joining mediated removal of a splice site mutation. In the case of a subject with a c.2657+5G>A mutation, the CF target position is 200 bp upstream and/or downstream of c.2657+5 within within exon 16, and intron 16 and intron 15. In the case of a subject with a c.3140-26A>G mutation, the CF target position is 200 bp upstream and/or downstream of c.3140-26 within exon 20 and intron 19. In an embodiment, in a subject with a target mutation in close proximity to an exon (including, but not limited to the mutations, e.g., 2789+5G>A, e.g., 3272-26A>G), approach may include Cas-9 mediated removal and/or disruption of an intronic segment at or near the target site with homology-directed repair with delivery of Cas9 nuclease (or nickase, or dead-Cas9), CRISPR-gRNAs, and homology-directed repair donor templates. In an embodiment, the donor template will be comprised of a single- strand oligonucleotide donor of 50 NT to 200 NT (or more as the technology becomes available). In an embodiment, the donor template will be comprised of a double- strand DNA donor with homology arms of length 700 bps to 1200 bps. The repair of a splice site mutation will restore accurate splicing and cease aberrant truncation of CFTR transcript. This approach will lead to the cessation of production of truncated CFTR channel and will lead to the production of wild-type CFTR channel. This approach will prevent the development or progression of lung,

gastrointestinal and/or reproductive disease in subjects with CFTR mutations.

In an embodiment, the method comprises the introduction of a double strand break sufficiently close to (e.g., either 5' or 3' to) the CF target position (e.g., c2657+5G>A, or c.3140- 26A>G), such that the break-induced indel could be reasonably expected to span the mutation. A single gRNAs, e.g., unimolecular (or chimeric) or modular gRNA molecules, is configured to position a double strand break sufficiently close to the CF target position in the CFTR gene (e.g., 2657+5G>A, or c.3140-26A>G). The double strand break may be positioned within 200

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5535.1 nucleotides (e.g., within 1, 2, 3, 4, 5, 10, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 100, or 200 nucleotides) upstream of the CF target poistion, or within 500 nucleotides (e.g., within 1, 2, 3, 4, 5, 10, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 100, or 200 nucleotides) downstream of the CF target position. While not wishing to be bound by theory, in an embodiment, it is believed that HDR mediated repair of the break(s) restores the functional CFTR protein.

In another embodiment, the method comprises the introduction of a pair of single strand breaks sufficiently close to (either 5' or 3' to, respectively) the mutation at the CF target position (e.g., c2657+5G>A, or c.3140-26A>G), such that the break- induced indel could be reasonably expected to span the mutation. Two gRNAs, e.g., unimolecular (or chimeric) or modular gRNA molecules, are configured to position the two single strand breaks sufficiently close to the CF target position in the CFTR gene. In an embodiment, the pair of single strand breaks is positioned within 500 nucleotides (e.g., within 1, 2, 3, 4, 5, 10, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 100, or 200 nucleotides) upstream of the CF target position, or within 500 nucleotides (e.g., within 1, 2, 3, 4, 5, 10, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 100, or 200 nucleotides)

downstream of the CF target position. While not wishing to be bound by theory, in an

embodiment, it is believed that HDR mediated repair of the break(s) restores the functional CFTR protein. In an embodiment, the pair of single strand breaks may be accompanied by an additional double strand break, positioned by a third gRNA molecule, as is discussed below. In another embodiment, the pair of single strand breaks may be accompanied by two additional single strand breaks positioned by a third gRNA molecule and a fourth gRNA molecule, as is discussed below.

In another embodiment, the method comprises the introduction of two sets of breaks (e.g., a pair of double strand breaks targeted by two gRNAs) sufficiently close to (either 5' or 3' to, respectively) the mutation at the CF target position (e.g., c2657+5G>A, or c.3140-26A>G), such that the break-induced indel could be reasonably expected to span the mutation. Two gRNAs, e.g., unimolecular (or chimeric) or modular gRNA molecules, are configured to position the two sets of breaks (e.g., a pair of double strand breaks) sufficiently close to the CF target position in the CFTR gene. In an embodiment, the pair of single strand breaks is positioned within 500 nucleotides (e.g., within 1, 2, 3, 4, 5, 10, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 100, or 200 nucleotides) upstream of the CF target position, or within 500 nucleotides (e.g., within 1, 2, 3, 4, 5, 10, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 100, or 200 nucleotides) downstream of the CF

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5535.1 target position. While not wishing to be bound by theory, in an embodiment, it is believed that HDR mediated repair of the break(s) restores the functional CFTR protein.

In another embodiment, the method comprises the introduction of two sets of breaks (e.g., one double strand break and a pair of single strand breaks targeted by three gRNAs) sufficiently close to (either 5' or 3' to, respectively) the mutation at the CF target position (e.g., c2657+5G>A, or c.3140-26A>G), such that the break- induced indel could be reasonably expected to span the mutation. Two gRNAs, e.g., unimolecular (or chimeric) or modular gRNA molecules, are configured to position the two sets of breaks (e.g., one double strand break and a pair of single strand breaks) sufficiently close to the CF target position in the CFTR gene. In an embodiment, the pair of single strand breaks is positioned within 500 nucleotides (e.g., within 1, 2, 3, 4, 5, 10, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 100, or 200 nucleotides) upstream of the CF target position, or within 500 nucleotides (e.g., within 1, 2, 3, 4, 5, 10, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 100, or 200 nucleotides) downstream of the CF target position. While not wishing to be bound by theory, in an embodiment, it is believed that HDR mediated repair of the break(s) restores the functional CFTR protein.

In another embodiment, the method comprises the introduction of two sets of breaks (e.g., two pairs of single strand breaks targeted by four gRNAs) sufficiently close to (either 5' or 3' to, respectively) the mutation at the CF target position (e.g., c2657+5G>A, or c.3140-26A>G), such that the break-induced indel could be reasonably expected to span the mutation. Two gRNAs, e.g., unimolecular (or chimeric) or modular gRNA molecules, are configured to position the two sets of breaks (e.g., two pairs of single strand breaks s) sufficiently close to the CF target position in the CFTR gene. In an embodiment, the pair of single strand breaks is positioned within 500 nucleotides (e.g., within 1, 2, 3, 4, 5, 10, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 100, or 200 nucleotides) upstream of the CF target position, or within 500 nucleotides (e.g., within 1, 2, 3, 4, 5, 10, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 100, or 200 nucleotides) downstream of the CF target position. While not wishing to be bound by theory, in an embodiment, it is believed that HDR mediated repair of the break(s) restores the functional CFTR protein.

In an embodiment, a single strand break is introduced (e.g., positioned by one gRNA molecule) at or in close proximity to a CF target position in the CFTR gene. In an embodiment, a single gRNA molecule (e.g., with a Cas9 nickase) is used to create a single strand break at or in close proximity to the CF target position, e.g., the gRNA is configured such that the single strand

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5535.1 break is positioned either upstream (e.g., within 200 bp upstream) or downstream (e.g., within 200 bp downstream) of the CF target position. In an embodiment, the break is positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, a double strand break is introduced (e.g., positioned by one gRNA molecule) at or in close proximity to a CF target position in the CFTR gene. In an embodiment, a single gRNA molecule (e.g., with a Cas9 nuclease other than a Cas9 nickase) is used to create a double strand break at or in close proximity to the CF target position, e.g., the gRNA molecule is configured such that the double strand break is positioned either upstream (e.g., within 200 bp upstream) or downstream of (e.g., within 200 bp downstream) of a CF target position. In an embodiment, the break is positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, two single strand breaks are introduced (e.g., positioned by two gRNA molecules) at or in close proximity to a CF target position in the CFTR gene. In an embodiment, two gRNA molecules (e.g., with one or two Cas9 nickcases) are used to create two single strand breaks at or in close proximity to the CF target position, e.g., the gRNAs molecules are configured such that both of the single strand breaks are positioned upstream (e.g., within 200 bp upstream) or downstream (e.g., within 200 bp downstream) of the CF target position. In another embodiment, two gRNA molecules (e.g., with two Cas9 nickcases) are used to create two single strand breaks at or in close proximity to the CF target position, e.g., the gRNAs molecules are configured such that one single strand break is positioned upstream (e.g., within 200 bp upstream) and a second single strand break is positioned downstream (e.g., within 200 bp downstream) of the CF target position. In an embodiment, the breaks are positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, two double strand breaks are introduced (e.g., positioned by two gRNA molecules) at or in close proximity to a CF target position in the CFTR gene. In an embodiment, two gRNA molecules (e.g., with one or two Cas9 nucleases that are not Cas9 nickases) are used to create two double strand breaks to flank a CF target position, e.g., the gRNA molecules are configured such that one double strand break is positioned upstream (e.g., within 200 bp upstream) and a second double strand break is positioned downstream (e.g., within 200 bp downstream) of the CF target position. In an embodiment, the breaks are positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

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5535.1 In an embodiment, one double strand break and two single strand breaks are introduced (e.g., positioned by three gRNA molecules) at or in close proximity to a CF target position in the CFTR gene. In an embodiment, three gRNA molecules (e.g., with a Cas9 nuclease other than a Cas9 nickase and one or two Cas9 nickases) to create one double strand break and two single strand breaks to flank an CF target position, e.g., the gRNA molecules are configured such that the double strand break is positioned upstream or downstream of (e.g., within 200 bp upstream or downstream) of the CF target position, and the two single strand breaks are positioned at the opposite site, e.g., downstream or upstream (within 200 bp downstream or upstream), of the CF target position. In an embodiment, the breaks are positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, four single strand breaks are introduced (e.g., positioned by four gRNA molecules) at or in close proximity to a CF target position in the CFTR gene. In an embodiment, four gRNA molecule (e.g., with one or more Cas9 nickases are used to create four single strand breaks to flank an CF target position in the CFTR gene, e.g., the gRNA molecules are configured such that a first and second single strand breaks are positioned upstream (e.g., within 200 bp upstream) of the CF target position, and a third and a fourth single stranded breaks are positioned downstream (e.g., within 200 bp downstream) of the CF target position. In an embodiment, the breaks are positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, two or more (e.g., three or four) gRNA molecules are used with one

Cas9 molecule. In another embodiment, when two or more (e.g., three or four) gRNAs are used with two or more Cas9 molecules, at least one Cas9 molecule is from a different species than the other Cas9 molecule(s). For example, when two gRNA molecules are used with two Cas9 molecules, one Cas9 molecule can be from one species and the other Cas9 molecule can be from a different species. Both Cas9 species are used to generate a single or double-strand break, as desired.

When two or more gRNAs are used to position two or more cleavage events, e.g., double strand or single strand breaks, in a target nucleic acid, it is contemplated that the two or more cleavage events may be made by the same or different Cas9 proteins. For example, when two gRNAs are used to position two double strand breaks, a single Cas9 nuclease may be used to create both double strand breaks. When two or more gRNAs are used to position two or more

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5535.1 single stranded breaks (single strand breaks), a single Cas9 nickase may be used to create the two or more single strand breaks. When two or more gRNAs are used to position at least one double strand break and at least one single strand break, two Cas9 proteins may be used, e.g., one Cas9 nuclease and one Cas9 nickase. It is contemplated that when two or more Cas9 proteins are used that the two or more Cas9 proteins may be delivered sequentially to control specificity of a double strand versus a single strand break at the desired position in the target nucleic acid.

In some embodiments, the targeting domain of the first gRNA molecule and the targeting domain of the second gRNA molecule hybridize to the target domain through complementary base pairing to opposite strands of the target nucleic acid molecule. In some embodiments, the gRNA molecule and the second gRNA molecule are configured such that the PAMs are oriented outward.

In an embodiment, the targeting domain of a gRNA molecule is configured to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat, or the endogenous CFTR splice sites, in the target domain. The gRNA molecule may be a first, second, third and/or fourth gRNA molecule.

In an embodiment, the targeting domain of a gRNA molecule is configured to position a cleavage event sufficiently far from a preselected nucleotide, e.g., the nucleotide of a coding region, such that the nucleotide is not altered. In an embodiment, the targeting domain of a gRNA molecule is configured to position an intronic cleavage event sufficiently far from an intron/exon border, or naturally occurring splice signal, to avoid alteration of the exonic sequence or unwanted splicing events. The gRNA molecule may be a first, second, third and/or fourth gRNA molecule, as described herein.

In an embodiment, the targeting domain of said gRNA molecule is configured to position a cleavage event sufficiently far from a preselected nucleotide, e.g., the nucleotide of a coding region, such that the nucleotide is not be altered. In an embodiment, the targeting domain of said gRNA molecule is configured to position an intronic cleavage event sufficiently far from an intron/exon border, or naturally occurring splice signal, to avoid alteration of the exonic sequence or unwanted splicing events.

Methods to Alter SCNN1A

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5535.1 As disclosed herein, the SCNNIA gene can be altered by gene editing, e.g., using CRISPR-Cas9 mediated methods as described herein. A CF or CF-like target position can be altered by gene editing, e.g., using CRISPR-Cas9 mediated methods to alter the SCNNIA gene. The alteration of the SCNNIA gene can be mediated by any mechanism. In an embodiment, CRISPR-Cas9 mediated methods to knockdown or knockout the SCNNIA gene may be applied to any subject with any CF mutation, including but not limited to, e.g., F508del, e.g., G551D, e.g., G542X, e.g., N1303K, e.g., R117H, e.g., W1282X, e.g., R553X, e.g., c.3717+12191, e.g., c.2657+5, e.g., C.3140-26A and/or any subject with any CF-like mutation, including but not limited to a SCNNIA mutation, e.g., VI 141. Exemplary mechanisms that can be associated with the alteration of the SCNNA1 gene include, but are not limited to, non-homologous end joining (e.g., classical or alternative), microhomology-mediated end joining (MMEJ), SDSA (synthesis dependent strand annealing) or single strand annealing or single strand invasion, all with or without the alteration of the CFTR gene, including but not limited to the addition of an endogenous- promoter driven cDNA encoding the CFTR gene, or homology-directed repair mediated correction of mutations within the CFTR gene or CRISPR-cas9 mediated repair of splice mutations within the CFTR gene.

As disclosed herein, the SCNNIA gene can be targeted (e.g., altered) by gene editing, e.g., using CRISPR-Cas9 mediated methods as described herein.

Methods and compositions discussed herein, provide for targeting (e.g., altering) a CF target position in the SCNNIA gene. A CF target position can be targeted (e.g., altered) by gene editing, e.g., using CRISPR-Cas9 mediated methods to target (e.g. alter) the SCNNIA gene.

Disclosed herein are methods for targeting (e.g., altering) a SCNNIA target position in the SCNNIA gene. Targeting (e.g., altering) the CF target position is achieved, e.g., by:

(1) knocking out the SCNNIA gene byinsertion or deletion (e.g., NHEJ-mediated insertion or deletion) of one or more nucleotides in close proximity to or within the early coding region of the SCNNIA gene, or

(2) knocking down the SCNNIA gene mediated by enzymatically inactive Cas9 (eiCas9) molecule or an eiCas9-fusion protein by targeting non-coding region, e.g., a promoter region, of the gene.

All approaches give rise to targeting (e.g., alteration) of the SCNNIA gene.

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5535.1 In an embodiment, methods described herein introduce one or more breaks near the early coding region in at least one allele of the SCNNIA gene. In another embodiment, methods described herein introduce two or more breaks to flank at least a portion of the SCNNIA gene. The two or more breaks remove (e.g., delete) a genomic sequence including at least a portion of the SCNNIA gene. In another embodiment, methods described herein comprise knocking down the SCNNIA gene mediated by enzymatically inactive Cas9 (eiCas9) molecule or an eiCas9- fusion protein by targeting the promoter region of SCNNIA target knockdown position. All methods described herein result in targeting (e.g., alteration) of the SCNNIA gene.

The targeting (e.g., alteration) of the SCNNIA gene can be mediated by any mechanism. Exemplary mechanisms that can be associated with the alteration of the SCNNIA gene include, but are not limited to, non-homologous end joining (e.g., classical or alternative),

microhomology-mediated end joining (MMEJ), homology-directed repair (e.g., endogenous donor template mediated), SDSA (synthesis dependent strand annealing), single strand annealing or single strand invasion.

Approach 4: Knocking out SCNNIA by introducing an indel or a deletion in the SCNNIA gene

In an embodiment, the method comprises introducing an insertion or deletion of one more nucleotides in close proximity to the SCNNIA target knockout position (e.g., the early coding region) of the SCNNIA gene. As described herein, in one embodiment, the method comprises the introduction of one or more breaks (e.g., single strand breaks or double strand breaks) sufficiently close to (e.g., either 5' or 3' to) the early coding region of the CF target knockout position, such that the break-induced indel could be reasonably expected to span the CF target knockout position (e.g., the early coding region in the SCNNIA gene). While not wishing to be bound by theory, it is believed that NHEJ-mediated repair of the break(s) allows for the NHEJ- mediated introduction of an indel in close proximity to within the early coding region of the CF target knockout position.

In an embodiment, the method comprises introducing a deletion of a genomic sequence comprising at least a portion of the SCNNIA gene. As described herein, in an embodiment, the method comprises the introduction of two double stand breaks - one 5' and the other 3' to (i.e., flanking) the CF target position. In an embodiment, two gRNAs, e.g., unimolecular (or

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5535.1 chimeric) or modular gRNA molecules, are configured to position the two double strand breaks on opposite sides of the CF target knockout position in the SCNN1A gene.

In an embodiment, a single strand break is introduced (e.g., positioned by one gRNA molecule) at or in close proximity to a CF target position in the SCNN1A gene. In an

embodiment, a single gRNA molecule (e.g., with a Cas9 nickase) is used to create a single strand break at or in close proximity to the CF target position, e.g., the gRNA is configured such that the single strand break is positioned either upstream (e.g., within 500 bp upstream, e.g., within 200 bp upstream) or downstream (e.g., within 500 bp downstream, e.g., within 200 bp downstream) of the CF target position. In an embodiment, the break is positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, a double strand break is introduced (e.g., positioned by one gRNA molecule) at or in close proximity to a CF target position in the SCNN1A gene. In an

embodiment, a single gRNA molecule (e.g., with a Cas9 nuclease other than a Cas9 nickase) is used to create a double strand break at or in close proximity to the CF target position, e.g., the gRNA molecule is configured such that the double strand break is positioned either upstream

(e.g., within 500 bp upstream, upstream) or downstream of (e.g., within 500 bp downstream) of a CF target position. In an embodiment, the break is positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, two single strand breaks are introduced (e.g., positioned by two gRNA molecules) at or in close proximity to a CF target position in the SCNN1A gene. In an embodiment, two gRNA molecules (e.g., with one or two Cas9 nickcases) are used to create two single strand breaks at or in close proximity to the CF target position, e.g., the gRNAs molecules are configured such that both of the single strand breaks are positioned e.g., within 500 bp upstream, upstream) or downstream (e.g., within 500 bp downstream downstream) of the CF target position. In another embodiment, two gRNA molecules (e.g., with two Cas9 nickcases) are used to create two single strand breaks at or in close proximity to the SCNN1A target position, e.g., the gRNAs molecules are configured such that one single strand break is positioned upstream (e.g., within 500 bp upstream) and a second single strand break is positioned downstream (e.g., within 500 bp downstream) of the SCNN1A target position. In an

embodiment, the breaks are positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

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5535.1 In an embodiment, two double strand breaks are introduced (e.g., positioned by two gRNA molecules) at or in close proximity to a CF target position in the SCNN1A gene. In an embodiment, two gRNA molecules (e.g., with one or two Cas9 nucleases that are not Cas9 nickases) are used to create two double strand breaks to flank a CF target position, e.g., the gRNA molecules are configured such that one double strand break is positioned upstream (e.g., within500 bp upstream) and a second double strand break is positioned downstream (e.g., within 500 bp downstream) of the SCNN1A target position. In an embodiment, the breaks are positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, one double strand break and two single strand breaks are introduced

(e.g., positioned by three gRNA molecules) at or in close proximity to a CF target position in the SCNN1A gene. In an embodiment, three gRNA molecules (e.g., with a Cas9 nuclease other than a Cas9 nickase and one or two Cas9 nickases) to create one double strand break and two single strand breaks to flank a CF target position, e.g., the gRNA molecules are configured such that the double strand break is positioned upstream or downstream of (e.g., within 500 bp upstreamor downstream) of the SCNN1A target position, and the two single strand breaks are positioned at the opposite site, e.g., downstream or upstrea m (e.g., within 500 bp downstream or upstream), of the CF target position. In an embodiment, the breaks are positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, four single strand breaks are introduced (e.g., positioned by four gRNA molecules) at or in close proximity to a CF target position in the SCNN1A gene. In an embodiment, four gRNA molecule (e.g., with one or more Cas9 nickases are used to create four single strand breaks to flank a CF target position in the SCNN1A gene, e.g., the gRNA molecules are configured such that a first and second single strand breaks are positioned upstream (e.g., within 500 bp upstream) of the CF target position, and a third and a fourth single stranded breaks are positioned downstream (e.g., within500 bp downstream) of the CF target position. In an embodiment, the breaks are positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, two or more (e.g., three or four) gRNA molecules are used with one Cas9 molecule. In another embodiment, when two ore more (e.g., three or four) gRNAs are used with two or more Cas9 molecules, at least one Cas9 molecule is from a different species than the

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5535.1 other Cas9 molecule(s). For example, when two gRNA molecules are used with two Cas9 molecules, one Cas9 molecule can be from one species and the other Cas9 molecule can be from a different species. Both Cas9 species are used to generate a single or double-strand break, as desired.

Approach 5: Knocking down SCNN1A mediated by an enzymatically inactive Cas9 (eiCas9) molecule

A targeted knockdown approach reduces or eliminates expression of functional SCNN1A gene product. As described herein, in an embodiment, a targeted knockdown is mediated by targeting an enzymatically inactive Cas9 (eiCas9) molecule or an eiCas9 fused to a transcription repressor domain or chromatin modifying protein to alter transcription, e.g., to block, reduce, or decrease transcription, of the SCNN1A gene.

Methods and compositions discussed herein may be used to alter the expression of the SCNN1A gene to treat or prevent CF or CF-like disease by targeting a promoter region of the SCNN1A gene. In an embodiment, the promoter region is targeted to knock down expression of the SCNN1A gene. A targeted knockdown approach reduces or eliminates expression of functional SCNN1A gene product. As described herein, in an embodiment, a targeted

knockdown is mediated by targeting an enzymatically inactive Cas9 (eiCas9) or an eiCas9 fused to a transcription repressor domain or chromatin modifying protein to alter transcription, e.g., to block, reduce, or decrease transcription, of the SCNN1A gene. In an embodiment, one or more eiCas9 molecules may be used to block binding of one or more endogenous transcription factors. In another embodiment, an eiCas9 molecule can be fused to a chromatin modifying protein. Altering chromatin status can result in decreased expression of the target gene. One or more eiCas9 molecules fused to one or more chromatin modifying proteins may be used to alter chromatin status.

An eiCas9mediated knock down of one of two SCNN1A allele/s by targeting the transcription start site of SCNN1A gene in exon I of all transcripts (including 500 bp upstream and downstream of transcription start site on all transcripts). This approach is performed in any subject with CF or CF-like disease, with or without a CFTR mutation and a WT or mutant SCNN1A. The CF or CF-like target position is at or near the transcription start site of the

SCNN1A gene. Or, altering the CF or CF-like target position refers to delivering a dCas9 that

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5535.1 sterically hinders transcription of either or both SCNNIA allele/s. This approach gives rise to the loss or destruction of transcription of the SCNNIA gene. This approach will lead to the reduction or cessation of production of ENaC. This approach will prevent the disinhibition of the ENaC channel in subjects with CF or CF-like disease. The viscosity of lung, gastrointestinal and reproductive tract mucous in subjects with CF or CF-like disease will not be further increased. This will lead to a reduction in viscosity of mucous within the lung, gastrointestinal and reproductive tract mucous in subjects with CF or CF-like disease. This approach will prevent the progression of CF and CF-like disease.

I. gRNA Molecules

A gRNA molecule, as that term is used herein, refers to a nucleic acid that promotes the specific targeting or homing of a gRNA molecule/Cas9 molecule complex to a target nucleic acid. gRNA molecules can be unimolecular (having a single RNA molecule), sometimes referred to herein as "chimeric" gRNAs, or modular (comprising more than one, and typically two, separate RNA molecules). A gRNA molecule comprises a number of domains. The gRNA molecule domains are described in more detail below.

Several exemplary gRNA structures, with domains indicated thereon, are provided in Figs. 1A-1G. While not wishing to be bound by theory, in an embodiment, with regard to the three dimensional form, or intra- or inter-strand interactions of an active form of a gRNA, regions of high complementarity are sometimes shown as duplexes in Figs. 1A-1G and other depictions provided herein.

In an embodiment, a unimolecular, or chimeric, gRNA comprises, preferably from 5' to

3':

a targeting domain (which is complementary to a target nucleic acid in the CFTR gene or SCNNIA gene, e.g., a targeting domain as described herein, e.g., a targeting domain from any of Tables 1A-1E, 2A-2E, 3A-3D, 4A-4D, 5A- 5E, 6A-6C, 7A-7D, 8A-8E, 9A-9B, lOA-lOC, 11A-11E, 12A-12C, 13A- 13D, 14A-14E, 15A-15C, or 16A-16D, 17A-17E, 18A-18C, 19A-19D, 20A-20E, 21A-21B, 22A-22D, 23A-23E, 24A-24D, 25A-25D, 26A-26E,

27A-27D, 28A-28D, 29A-29E, 30A-30B, 31A-31D, 32A-32D, 33A-33B,

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5535.1 34A-34D, 35A-35D, 36A-36D, 37A-37D, 38A-38E, 39A-39D, 40A-40D, 41A-41E, 42A-42D, 43A-43E, 44A-44G, 45A-45E, 46A-46E, 47A-47G, and 48A-48E;

a first complementarity domain;

a linking domain;

a second complementarity domain (which is complementary to the first

complementarity domain);

a proximal domain; and

optionally, a tail domain.

In an embodiment, a modular gRNA comprises:

a first strand comprising, preferably from 5' to 3' ;

a targeting domain (which is complementary to a target nucleic acid in the CFTR gene or SCNNIA gene, e.g., a targeting domain as described herein, e.g., a targeting domain from any of Tables 1A-1E, 2A-2E, 3A-3D, 4A-4D, 5A-5E, 6A- 6C, 7A-7D, 8A-8E, 9A-9B, lOA-lOC, 11A-11E, 12A-12C, 13A-13D, 14A-14E, 15A-15C, or 16A-16D, 17A-17E, 18A-18C, 19A-19D, 20A-20E, 21A-21B, 22A-22D, 23A-23E, 24A-24D, 25A-25D, 26A-26E, 27A-27D, 28A-28D, 29A- 29E, 30A-30B, 31A-31D, 32A-32D, 33A-33B, 34A-34D, 35A-35D, 36A-36D, 37A-37D, 38A-38E, 39A-39D, 40A-40D, 41A-41E, 42A-42D, 43A-43E, 44A- 44G, 45A-45E, 46A-46E, 47A-47G, or 48A-48E); and

a first complementarity domain; and

a second strand, comprising, preferably from 5' to 3':

optionally, a 5' extension domain;

a second complementarity domain;

a proximal domain; and

optionally, a tail domain.

The domains are discussed briefly below.

The Targeting Domain Figs. 1A-1G provide examples of the placement of targeting domains.

The targeting domain comprises a nucleotide sequence that is complementary, e.g., at least 80, 85, 90, or 95% complementary, e.g., fully complementary, to the target sequence on the target nucleic acid. The targeting domain is part of an RNA molecule and will therefore comprise the base uracil (U), while any DNA encoding the gRNA molecule will comprise the base thymine (T). While not wishing to be bound by theory, in an embodiment, it is believed that the complementarity of the targeting domain with the target sequence contributes to specificity of the interaction of the gRNA molecule/Cas9 molecule complex with a target nucleic acid. It is understood that in a targeting domain and target sequence pair, the uracil bases in the targeting domain will pair with the adenine bases in the target sequence. In an embodiment, the target domain itself comprises in the 5' to 3' direction, an optional secondary domain, and a core domain. In an embodiment, the core domain is fully complementary with the target sequence. In an embodiment, the targeting domain is 5 to 50 nucleotides in length. The strand of the target nucleic acid with which the targeting domain is complementary is referred to herein as the complementary strand. Some or all of the nucleotides of the domain can have a modification, e.g., a modification found in Section VIII herein.

In an embodiment, the targeting domain is 16 nucleotides in length.

In an embodiment, the targeting domain is 17 nucleotides in length.

In an embodiment, the targeting domain is 18 nucleotides in length.

In an embodiment, the targeting domain is 19 nucleotides in length.

In an embodiment, the targeting domain is 20 nucleotides in length.

In an embodiment, the targeting domain is 21 nucleotides in length.

In an embodiment, the targeting domain is 22 nucleotides in length.

In an embodiment, the targeting domain is 23 nucleotides in length.

In an embodiment, the targeting domain is 24 nucleotides in length.

In an embodiment, the targeting domain is 25 nucleotides in length.

In an embodiment, the targeting domain is 26 nucleotides in length.

In an embodiment, the targeting domain comprises 16 nucleotides.

In an embodiment, the targeting domain comprises 17 nucleotides.

In an embodiment, the targeting domain comprises 18 nucleotides.

In an embodiment, the targeting domain comprises 19 nucleotides.

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5535.1 In an embodiment, the targeting domain comprises 20 nucleotides.

In an embodiment, the targeting domain comprises 21 nucleotides.

In an embodiment, the targeting domain comprises 22 nucleotides.

In an embodiment, the targeting domain comprises 23 nucleotides.

In an embodiment, the targeting domain comprises 24 nucleotides.

In an embodiment, the targeting domain comprises 25 nucleotides.

In an embodiment, the targeting domain comprises 26 nucleotides.

Targeting domains are discussed in more detail below. The First Complementarity Domain

Figs. 1A-1G provide examples of first complementarity domains.

The first complementarity domain is complementary with the second complementarity domain, and in an embodiment, has sufficient complementarity to the second complementarity domain to form a duplexed region under at least some physiological conditions. In an embodiment, the first complementarity domain is 5 to 30 nucleotides in length. In an

embodiment, the first complementarity domain is 5 to 25 nucleotides in length. In an

embodiment, the first complementary domain is 7 to 25 nucleotides in length. In an

embodiment, the first complementary domain is 7 to 22 nucleotides in length. In an

embodiment, the first complementary domain is 7 to 18 nucleotides in length. In an

embodiment, the first complementary domain is 7 to 15 nucleotides in length. In an

embodiment, the first complementary domain is 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25 nucleotides in length.

In an embodiment, the first complementarity domain comprises 3 subdomains, which, in the 5' to 3' direction are: a 5' subdomain, a central subdomain, and a 3' subdomain. In an embodiment, the 5' subdomain is 4 to 9, e.g., 4, 5, 6, 7, 8 or 9 nucleotides in length. In an embodiment, the central subdomain is 1, 2, or 3, e.g., 1, nucleotide in length. In an embodiment, the 3' subdomain is 3 to 25, e.g., 4 to 22, 4 to 18, or 4 to 10, or 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25 nucleotides in length.

The first complementarity domain can share homology with, or be derived from, a naturally occurring first complementarity domain. In an embodiment, it has at least 50%

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5535.1 homology with a first complementarity domain disclosed herein, e.g., an S. pyogenes, S. aureus or S. thermophilus, first complementarity domain.

Some or all of the nucleotides of the domain can have a modification, e.g., a modification found in Section VIII herein.

First complementarity domains are discussed in more detail below.

The Linking Domain

Figs. 1A-1G provide examples of linking domains.

A linking domain serves to link the first complementarity domain with the second complementarity domain of a unimolecular gRNA. The linking domain can link the first and second complementarity domains covalently or non-covalently. In an embodiment, the linkage is covalent. In an embodiment, the linking domain covalently couples the first and second complementarity domains, see, e.g., Figs. IB-IE. In an embodiment, the linking domain is, or comprises, a covalent bond interposed between the first complementarity domain and the second complementarity domain. Typically the linking domain comprises one or more, e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10 nucleotides.

In modular gRNA molecules the two molecules are associated by virtue of the

hybridization of the complementarity domains see e.g., Fig. 1A.

A wide variety of linking domains are suitable for use in unimolecular gRNA molecules. Linking domains can consist of a covalent bond, or be as short as one or a few nucleotides, e.g., 1, 2, 3, 4, or 5 nucleotides in length. In an embodiment, a linking domain is 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, or 25 or more nucleotides in length. In an embodiment, a linking domain is 2 to 50, 2 to 40, 2 to 30, 2 to 20, 2 to 10, or 2 to 5 nucleotides in length. In an embodiment, a linking domain shares homology with, or is derived from, a naturally occurring sequence, e.g., the sequence of a tracrRNA that is 5' to the second complementarity domain. In an embodiment, the linking domain has at least 50% homology with a linking domain disclosed herein.

Some or all of the nucleotides of the domain can have a modification, e.g., a modification found in Section VIII herein.

Linking domains are discussed in more detail below.

The 5' Extension Domain

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5535.1 In an embodiment, a modular gRNA can comprise additional sequence, 5' to the second complementarity domain, referred to herein as the 5' extension domain, see, e.g., Fig. 1A. In an embodiment, the 5' extension domain is, 2 to 10, 2 to 9, 2 to 8, 2 to 7, 2 to 6, 2 to 5, 2 to 4 nucleotides in length. In an embodiment, the 5' extension domain is 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more nucleotides in length.

The Second Complementarity Domain

Figs. 1A-1G provide examples of second complementarity domains.

The second complementarity domain is complementary with the first complementarity domain, and in an embodiment, has sufficient complementarity to the second complementarity domain to form a duplexed region under at least some physiological conditions. In an embodiment, e.g., as shown in Figs. 1A-1B, the second complementarity domain can include sequence that lacks complementarity with the first complementarity domain, e.g., sequence that loops out from the duplexed region.

In an embodiment, the second complementarity domain is 5 to 27 nucleotides in length.

In an embodiment, it is longer than the first complementarity region. In an embodiment the second complementary domain is 7 to 27 nucleotides in length. In an embodiment, the second complementary domain is 7 to 25 nucleotides in length. In an embodiment, the second complementary domain is 7 to 20 nucleotides in length. In an embodiment, the second complementary domain is 7 to 17 nucleotides in length. In an embodiment, the complementary domain is 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 or 25 nucleotides in length.

In an embodiment, the second complementarity domain comprises 3 subdomains, which, in the 5' to 3' direction are: a 5' subdomain, a central subdomain, and a 3' subdomain. In an embodiment, the 5' subdomain is 3 to 25, e.g., 4 to 22, 4 tol8, or 4 to 10, or 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25 nucleotides in length. In an embodiment, the central subdomain is 1, 2, 3, 4 or 5, e.g., 3, nucleotides in length. In an embodiment, the 3' subdomain is 4 to 9, e.g., 4, 5, 6, 7, 8 or 9 nucleotides in length.

In an embodiment, the 5' subdomain and the 3' subdomain of the first complementarity domain, are respectively, complementary, e.g., fully complementary, with the 3' subdomain and the 5' subdomain of the second complementarity domain.

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5535.1 The second complementarity domain can share homology with or be derived from a naturally occurring second complementarity domain. In an embodiment, it has at least 50% homology with a second complementarity domain disclosed herein, e.g., an S. pyogenes, S. aureus or S. thermophilus, first complementarity domain.

Some or all of the nucleotides of the domain can have a modification, e.g., a modification found in Section VIII herein.

A Proximal domain

Figs. 1A-1G provide examples of proximal domains.

In an embodiment, the proximal domain is 5 to 20 nucleotides in length. In an embodiment, the proximal domain can share homology with or be derived from a naturally occurring proximal domain. In an embodiment, it has at least 50% homology with a proximal domain disclosed herein, e.g., an S. pyogenes, S. aureus or S. thermophilus, proximal domain.

Some or all of the nucleotides of the domain can have a modification, e.g., a modification found in Section VIII herein.

A Tail Domain

Figs. 1A-1G provide examples of tail domains.

As can be seen by inspection of the tail domains in Figs. 1A-1E, a broad spectrum of tail domains are suitable for use in gRNA molecules. In an embodiment, the tail domain is 0 (absent), 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 nucleotides in length. In embodiment, the tail domain nucleotides are from or share homology with sequence from the 5' end of a naturally occurring tail domain, see e.g., Fig. ID or Fig. IE. In an embodiment, the tail domain includes sequences that are complementary to each other and which, under at least some physiological conditions, form a duplexed region.

In an embodiment, the tail domain is absent or is 1 to 50 nucleotides in length. In an embodiment, the tail domain can share homology with or be derived from a naturally occurring proximal tail domain. In an embodiment, it has at least 50% homology with a tail domain disclosed herein, e.g., an S. pyogenes, S. aureus or S. thermophilus, tail domain.

In an embodiment, the tail domain includes nucleotides at the 3' end that are related to the method of in vitro or in vivo transcription. When a T7 promoter is used for in vitro

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5535.1 transcription of the gRNA, these nucleotides may be any nucleotides present before the 3' end of the DNA template. When a U6 promoter is used for in vivo transcription, these nucleotides may be the sequence UUUUUU. When alternate pol-III promoters are used, these nucleotides may be various numbers or uracil bases or may include alternate bases.

The domains of gRNA molecules are described in more detail below.

The Targeting Domain

The "targeting domain" of the gRNA is complementary to the "target domain" on the target nucleic acid. The strand of the target nucleic acid comprising the nucleotide sequence complementary to the core domain of the gRNA is referred to herein as the "complementary strand" of the target nucleic acid. Guidance on the selection of targeting domains can be found, e.g., in Fu Y et al, Nat Biotechnol 2014 (doi: 10.1038/nbt.2808) and Sternberg SH et al., Nature 2014 (doi: 10.1038/naturel3011).

In an embodiment, the targeting domain is 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or 26 nucleotides in length.

In an embodiment, the targeting domain is 16 nucleotides in length.

In an embodiment, the targeting domain is 17 nucleotides in length.

In an embodiment, the targeting domain is 18 nucleotides in length.

In an embodiment, the targeting domain is 19 nucleotides in length.

In an embodiment, the targeting domain is 20 nucleotides in length.

In an embodiment, the targeting domain is 21 nucleotides in length.

In an embodiment, the targeting domain is 22 nucleotides in length.

In an embodiment, the targeting domain is 23 nucleotides in length.

In an embodiment, the targeting domain is 24 nucleotides in length.

In an embodiment, the targeting domain is 25 nucleotides in length.

In an embodiment, the targeting domain is 26 nucleotides in length.

In an embodiment, the targeting domain comprises 16 nucleotides.

In an embodiment, the targeting domain comprises 17 nucleotides.

In an embodiment, the targeting domain comprises 18 nucleotides.

In an embodiment, the targeting domain comprises 19 nucleotides.

In an embodiment, the targeting domain comprises 20 nucleotides.

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5535.1 In an embodiment, the targeting domain comprises 21 nucleotides.

In an embodiment, the targeting domain comprises 22 nucleotides.

In an embodiment, the targeting domain comprises 23 nucleotides.

In an embodiment, the targeting domain comprises 24 nucleotides.

In an embodiment, the targeting domain comprises 25 nucleotides.

In an embodiment, the targeting domain comprises 26 nucleotides.

In an embodiment, the targeting domain is 10 +/-5, 20+/-5, 30+/-5, 40+/-5, 50+/-5, 60+/- 5, 70+/-5, 80+/-5, 90+/-5, or 100+/-5 nucleotides, in length.

In an embodiment, the targeting domain is 20+/-5 nucleotides in length.

In an embodiment, the targeting domain is 20+/- 10, 30+/- 10, 40+/- 10, 50+/- 10, 60+/- 10,

70+/- 10, 80+/- 10, 90+/- 10, or 100+/- 10 nucleotides, in length.

In an embodiment, the targeting domain is 30+/- 10 nucleotides in length.

In an embodiment, the targeting domain is 10 to 100, 10 to 90, 10 to 80, 10 to 70, 10 to 60, 10 to 50, 10 to 40, 10 to 30, 10 to 20 or 10 to 15 nucleotides in length. In another embodiment, the targeting domain is 20 to 100, 20 to 90, 20 to 80, 20 to 70, 20 to 60, 20 to 50, 20 to 40, 20 to 30, or 20 to 25 nucleotides in length.

Typically the targeting domain has full complementarity with the target sequence. In an embodiment the targeting domain has or includes 1, 2, 3, 4, 5, 6, 7 or 8 nucleotides that are not complementary with the corresponding nucleotide of the targeting domain.

In an embodiment, the target domain includes 1, 2, 3, 4 or 5 nucleotides that are complementary with the corresponding nucleotide of the targeting domain within 5 nucleotides of its 5' end. In an embodiment, the target domain includes 1, 2, 3, 4 or 5 nucleotides that are complementary with the corresponding nucleotide of the targeting domain within 5 nucleotides of its 3' end.

In an embodiment, the target domain includes 1, 2, 3, or 4 nucleotides that are not complementary with the corresponding nucleotide of the targeting domain within 5 nucleotides of its 5' end. In an embodiment, the target domain includes 1, 2, 3, or 4 nucleotides that are not complementary with the corresponding nucleotide of the targeting domain within 5 nucleotides of its 3' end.

In an embodiment, the degree of complementarity, together with other properties of the gRNA, is sufficient to allow targeting of a Cas9 molecule to the target nucleic acid.

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5535.1 In an embodiment, the targeting domain comprises two consecutive nucleotides that are not complementary to the target domain ("non-complementary nucleotides"), e.g., two consecutive noncomplementary nucleotides that are within 5 nucleotides of the 5' end of the targeting domain, within 5 nucleotides of the 3' end of the targeting domain, or more than 5 nucleotides away from one or both ends of the targeting domain.

In an embodiment, no two consecutive nucleotides within 5 nucleotides of the 5' end of the targeting domain, within 5 nucleotides of the 3' end of the targeting domain, or within a region that is more than 5 nucleotides away from one or both ends of the targeting domain, are not complementary to the targeting domain.

In an embodiment, there are no noncomplementary nucleotides within 5 nucleotides of the 5' end of the targeting domain, within 5 nucleotides of the 3' end of the targeting domain, or within a region that is more than 5 nucleotides away from one or both ends of the targeting domain.

In an embodiment, the targeting domain nucleotides do not comprise modifications, e.g., modifications of the type provided in Section VIII. However, in an embodiment, the targeting domain comprises one or more modifications, e.g., modifications that it render it less susceptible to degradation or more bio-compatible, e.g., less immunogenic. By way of example, the backbone of the targeting domain can be modified with a phosphorothioate, or other

modification(s) from Section VIII. In an embodiment, a nucleotide of the targeting domain can comprise a 2' modification, e.g., a 2-acetylation, e.g., a 2' methylation, or other modification(s) from Section VIII.

In an embodiment, the targeting domain includes 1, 2, 3, 4, 5, 6, 7 or 8 or more modifications. In an embodiment, the targeting domain includes 1, 2, 3, or 4 modifications within 5 nucleotides of its 5' end. In an embodiment, the targeting domain comprises as many as 1, 2, 3, or 4 modifications within 5 nucleotides of its 3' end.

In an embodiment, the targeting domain comprises modifications at two consecutive nucleotides, e.g., two consecutive nucleotides that are within 5 nucleotides of the 5' end of the targeting domain, within 5 nucleotides of the 3' end of the targeting domain, or more than 5 nucleotides away from one or both ends of the targeting domain.

In an embodiment, no two consecutive nucleotides are modified within 5 nucleotides of the 5' end of the targeting domain, within 5 nucleotides of the 3' end of the targeting domain, or

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5535.1 within a region that is more than 5 nucleotides away from one or both ends of the targeting domain. In an embodiment, no nucleotide is modified within 5 nucleotides of the 5' end of the targeting domain, within 5 nucleotides of the 3' end of the targeting domain, or within a region that is more than 5 nucleotides away from one or both ends of the targeting domain.

Modifications in the targeting domain can be selected so as to not interfere with targeting efficacy, which can be evaluated by testing a candidate modification in the system described in Section IV. gRNAs having a candidate targeting domain having a selected length, sequence, degree of complementarity, or degree of modification, can be evaluated in a system in Section IV. The candidate targeting domain can be placed, either alone, or with one or more other candidate changes in a gRNA molecule/Cas9 molecule system known to be functional with a selected target and evaluated.

In an embodiment, all of the modified nucleotides are complementary to and capable of hybridizing to corresponding nucleotides present in the target domain. In another embodiment,

I, 2, 3, 4, 5, 6, 7 or 8 or more modified nucleotides are not complementary to or capable of hybridizing to corresponding nucleotides present in the target domain.

In an embodiment, the targeting domain comprises, preferably in the 5'→3' direction: a secondary domain and a core domain. These domains are discussed in more detail below.

The Core Domain and Secondary Domain of the Targeting Domain

The "core domain" of the targeting domain is complementary to the "core domain target" on the target nucleic acid. In an embodiment, the core domain comprises about 8 to about 13 nucleotides from the 3' end of the targeting domain (e.g., the most 3' 8 to 13 nucleotides of the targeting domain).

In an embodiment, the core domain and targeting domain, are independently, 6 +1-2, 1+1- 2, 8+/-2, 9+/-2, 10+/-2, 11+/-2, 12+/-2, 13+/-2, 14+/-2, 15+/-2, or 16+-2, nucleotides in length.

In an embodiment, the core domain and targeting domain, are independently, 10+/-2 nucleotides in length.

In an embodiment, the core domain and targeting domain, are independently, 10+/-4 nucleotides in length.

In an embodiment, the core domain and targeting domain are independently 6, 7, 8, 9, 10,

I I, 12, 13, 14, 15, 16, 17, or 18 nucleotides in length.

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5535.1 In an embodiment, the core domain and targeting domain are independently 3 to 20, 4 to 20, 5 to 20, 6 to 20, 7 to 20, 8 to 20, 9 to 20 10 to 20 or 15 to 20 nucleotides in length.

In an embodiment, the core domain and targeting domain are independently 3 to 15, e.g., 6 to 15, 7 to 14, 7 to 13, 6 to 12, 7 to 12, 7 to 11, 7 to 10, 8 to 14, 8 to 13, 8 to 12, 8 to 11, 8 to 10 or 8 to 9 nucleotides in length.

The core domain is complementary with the core domain target. Typically the core domain has exact complementarity with the core domain target. In some embodiments, the core domain can have 1, 2, 3, 4 or 5 nucleotides that are not complementary with the corresponding nucleotide of the core domain. In an embodiment, the degree of complementarity, together with other properties of the gRNA, is sufficient to allow targeting of a Cas9 molecule to the target nucleic acid.

The "secondary domain" of the targeting domain of the gRNA is complementary to the "secondary domain target" of the target nucleic acid.

In an embodiment, the secondary domain is positioned 5' to the core domain.

In an embodiment, the secondary domain is absent or optional.

In an embodiment, if the targeting domain is 26 nucleotides in length and the core domain (counted from the 3' end of the targeting domain) is 8 to 13 nucleotides in length, the secondary domain is 12 to 17 nucleotides in length.

In an embodiment, if the targeting domain is 25 nucleotides in length and the core domain (counted from the 3' end of the targeting domain) is 8 to 13 nucleotides in length, the secondary domain is 12 to 17 nucleotides in length.

In an embodiment, if the targeting domain is 24 nucleotides in length and the core domain (counted from the 3' end of the targeting domain) is 8 to 13 nucleotides in length, the secondary domain is 11 to 16 nucleotides in length.

In an embodiment, if the targeting domain is 23 nucleotides in length and the core domain (counted from the 3' end of the targeting domain) is 8 to 13 nucleotides in length, the secondary domain is 10 to 15 nucleotides in length.

In an embodiment, if the targeting domain is 22 nucleotides in length and the core domain (counted from the 3' end of the targeting domain) is 8 to 13 nucleotides in length, the secondary domain is 9 to 14 nucleotides in length.

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5535.1 In an embodiment, if the targeting domain is 21 nucleotides in length and the core domain (counted from the 3' end of the targeting domain) is 8 to 13 nucleotides in length, the secondary domain is 8 to 13 nucleotides in length.

In an embodiment, if the targeting domain is 20 nucleotides in length and the core domain (counted from the 3' end of the targeting domain) is 8 to 13 nucleotides in length, the secondary domain is 7 to 12 nucleotides in length.

In an embodiment, if the targeting domain is 19 nucleotides in length and the core domain (counted from the 3' end of the targeting domain) is 8 to 13 nucleotides in length, the secondary domain is 6 to 11 nucleotides in length.

In an embodiment, if the targeting domain is 18 nucleotides in length and the core domain (counted from the 3' end of the targeting domain) is 8 to 13 nucleotides in length, the secondary domain is 5 to 10 nucleotides in length.

In an embodiment, if the targeting domain is 17 nucleotides in length and the core domain (counted from the 3' end of the targeting domain) is 8 to 13 nucleotides in length, the secondary domain is 4 to 9 nucleotides in length.

In an embodiment, if the targeting domain is 16 nucleotides in length and the core domain (counted from the 3' end of the targeting domain) is 8 to 13 nucleotides in length, the secondary domain is 3 to 8 nucleotides in length.

In an embodiment, the secondary domain is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 nucleotides in length.

The secondary domain is complementary with the secondary domain target. Typically the secondary domain has exact complementarity with the secondary domain target. In an embodiment, the secondary domain can have 1, 2, 3, 4 or 5 nucleotides that are not

complementary with the corresponding nucleotide of the secondary domain. In an embodiment, the degree of complementarity, together with other properties of the gRNA, is sufficient to allow targeting of a Cas9 molecule to the target nucleic acid.

In an embodiment, the core domain nucleotides do not comprise modifications, e.g., modifications of the type provided in Section VIII. However, in an embodiment, the core domain comprises one or more modifications, e.g., modifications that it render it less susceptible to degradation or more bio-compatible, e.g., less immunogenic. By way of example, the backbone of the core domain can be modified with a phosphorothioate, or other modification(s)

100

5535.1 from Section VIII. In an embodiment a nucleotide of the core domain can comprise a 2' modification, e.g., a 2-acetylation, e.g., a 2' methylation, or other modification(s) from Section VIII. Typically, a core domain will contain no more than 1, 2, or 3 modifications.

Modifications in the core domain can be selected so as to not interfere with targeting efficacy, which can be evaluated by testing a candidate modification in the system described in Section IV. gRNAs having a candidate core domain having a selected length, sequence, degree of complementarity, or degree of modification, can be evaluated in the system described at Section IV. The candidate core domain can be placed, either alone, or with one or more other candidate changes in a gRNA molecule/Cas9 molecule system known to be functional with a selected target and evaluated.

In an embodiment, the secondary domain nucleotides do not comprise modifications, e.g., modifications of the type provided in Section VIII. However, in an embodiment, the secondary domain comprises one or more modifications, e.g., modifications that render it less susceptible to degradation or more bio-compatible, e.g., less immunogenic. By way of example, the backbone of the secondary domain can be modified with a phosphorothioate, or other modification(s) from Section VIII. In an embodiment a nucleotide of the secondary domain can comprise a 2' modification, e.g., a 2-acetylation, e.g., a 2' methylation, or other modification(s) from Section VIII. Typically, a secondary domain will contain no more than 1, 2, or 3 modifications.

Modifications in the secondary domain can be selected so as to not interfere with targeting efficacy, which can be evaluated by testing a candidate modification in the system described in Section IV. gRNAs having a candidate secondary domain having a selected length, sequence, degree of complementarity, or degree of modification, can be evaluated in the system described at Section IV. The candidate secondary domain can be placed, either alone, or with one or more other candidate changes in a gRNA molecule/Cas9 molecule system known to be functional with a selected target and evaluated.

In an embodiment, (1) the degree of complementarity between the core domain and its target, and (2) the degree of complementarity between the secondary domain and its target, may differ. In an embodiment, (1) may be greater than (2). In an embodiment, (1) may be less than (2). In an embodiment, (1) and (2) are the same, e.g., each may be completely complementary with its target.

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5535.1 In an embodiment, (1) the number of modifications (e.g., modifications from Section VIII) of the nucleotides of the core domain and (2) the number of modifications (e.g., modifications from Section VIII) of the nucleotides of the secondary domain may differ. In an embodiment, (1) may be less than (2). In an embodiment, (1) may be greater than (2). In an embodiment, (1) and (2) may be the same, e.g., each may be free of modifications.

The First and Second Complementarity Domains

The first complementarity domain is complementary with the second complementarity domain.

Typically the first domain does not have exact complementarity with the second complementarity domain target. In some embodiments, the first complementarity domain can have 1, 2, 3, 4 or 5 nucleotides that are not complementary with the corresponding nucleotide of the second complementarity domain. In an embodiment, 1, 2, 3, 4, 5 or 6, e.g., 3 nucleotides, will not pair in the duplex, and, e.g., form a non-duplexed or looped-out region. In an embodiment, an unpaired, or loop-out, region, e.g., a loop-out of 3 nucleotides, is present on the second complementarity domain. In an embodiment, the unpaired region begins 1, 2, 3, 4, 5, or 6, e.g., 4, nucleotides from the 5' end of the second complementarity domain.

In an embodiment, the degree of complementarity, together with other properties of the gRNA, is sufficient to allow targeting of a Cas9 molecule to the target nucleic acid.

In an embodiment, the first and second complementarity domains are:

independently, 6 +1-2, 1+1-2, 8+/-2, 9+1-2, 10+/-2, 11+/-2, 12+/-2, 13+/-2, 14+/-2, 15+/-2, 16+/-2, 17+/-2, 18+/-2, 19+/-2, or 20+/-2, 21+/-2, 22+/-2, 23+/-2, or 24+/-2 nucleotides in length;

independently, 6, 7, 8, 9, 10, 11, 12, 13, 14, 14, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, or 26, nucleotides in length; or

independently, 5 to 24, 5 to 23, 5 to 22, 5 to 21, 5 to 20, 7 to 18, 9 to 16, or 10 to 14 nucleotides in length.

In an embodiment, the second complementarity domain is longer than the first complementarity domain, e.g., 2, 3, 4, 5, or 6, e.g., 6, nucleotides longer.

In an embodiment, the first and second complementary domains, independently, do not comprise modifications, e.g., modifications of the type provided in Section VIII.

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5535.1 In an embodiment, the first and second complementary domains, independently, comprise one or more modifications, e.g., modifications that the render the domain less susceptible to degradation or more bio-compatible, e.g., less immunogenic. By way of example, the backbone of the domain can be modified with a phosphorothioate, or other modification(s) from Section VIII. In an embodiment a nucleotide of the domain can comprise a 2'

modification, e.g., a 2-acetylation, e.g., a 2' methylation, or other modification(s) from Section VIII.

In an embodiment, the first and second complementary domains, independently, include 1, 2, 3, 4, 5, 6, 7 or 8 or more modifications. In an embodiment, the first and second

complementary domains, independently, include 1, 2, 3, or 4 modifications within 5 nucleotides of its 5' end. In an embodiment, the first and second complementary domains, independently, include as many as 1, 2, 3, or 4 modifications within 5 nucleotides of its 3' end.

In an embodiment, the first and second complementary domains, independently, include modifications at two consecutive nucleotides, e.g., two consecutive nucleotides that are within 5 nucleotides of the 5' end of the domain, within 5 nucleotides of the 3' end of the domain, or more than 5 nucleotides away from one or both ends of the domain. In an embodiment, the first and second complementary domains, independently, include no two consecutive nucleotides that are modified, within 5 nucleotides of the 5' end of the domain, within 5 nucleotides of the 3' end of the domain, or within a region that is more than 5 nucleotides away from one or both ends of the domain. In an embodiment, the first and second complementary domains, independently, include no nucleotide that is modified within 5 nucleotides of the 5' end of the domain, within 5 nucleotides of the 3' end of the domain, or within a region that is more than 5 nucleotides away from one or both ends of the domain.

Modifications in a complementarity domain can be selected so as to not interfere with targeting efficacy, which can be evaluated by testing a candidate modification in the system described in Section IV. gRNAs having a candidate complementarity domain having a selected length, sequence, degree of complementarity, or degree of modification, can be evaluated in the system described in Section IV. The candidate complementarity domain can be placed, either alone, or with one or more other candidate changes in a gRNA molecule/Cas9 molecule system known to be functional with a selected target and evaluated.

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5535.1 In an embodiment, the first complementarity domain has at least 60, 70, 80, 85%, 90% or 95% homology with, or differs by no more than 1, 2, 3, 4, 5, or 6 nucleotides from, a reference first complementarity domain, e.g., a naturally occurring, e.g., an S. pyogenes, S. aureus or S. thermophilus, first complementarity domain, or a first complementarity domain described herein, e.g., from Figs. 1A-1G.

In an embodiment, the second complementarity domain has at least 60, 70, 80, 85%, 90%, or 95% homology with, or differs by no more than 1, 2, 3, 4, 5, or 6 nucleotides from, a reference second complementarity domain, e.g., a naturally occurring, e.g., an S. pyogenes, S. aureus or S. thermophilus, second complementarity domain, or a second complementarity domain described herein, e.g., from Figs. 1A-1G.

The duplexed region formed by first and second complementarity domains is typically 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 or 22 base pairs in length (excluding any looped out or unpaired nucleotides).

In some embodiments, the first and second complementarity domains, when duplexed, comprise 11 paired nucleotides, for example, in the gRNA sequence (one paired strand underlined, one bolded):

NNNNNNNNNNNNNNNNNNNNGUUUUAGAGCUAGAAAUAGCAAGUUAAAAUAAGG CUAGUCCGUUAUCAACUUGAAAAAGUGGCACCGAGUCGGUGC (SEQ ID NO: 5).

In some embodiments, the first and second complementarity domains, when duplexed, comprise 15 paired nucleotides, for example in the gRNA sequence (one paired strand underlined, one bolded):

NNNNNNNNNNNNNNNNNNNNGUUUUAGAGCUAUGCUGAAAAGCAUAGCAAGUUA AAAUAAGGCUAGUCCGUUAUCAACUUGAAAAAGUGGCACCGAGUCGGUGC (SEQ ID NO: 27).

In some embodiments the first and second complementarity domains, when duplexed, comprise 16 paired nucleotides, for example in the gRNA sequence (one paired strand underlined, one bolded):

NNNNNNNNNNNNNNNNNNNNGUUUUAGAGCUAUGCUGGAAACAGCAUAGCAAGU UAAAAUAAGGCUAGUCCGUUAUCAACUUGAAAAAGUGGCACCGAGUCGGUGC

(SEQ ID NO: 28).

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5535.1 In some embodiments the first and second complementarity domains, when duplexed, comprise 21 paired nucleotides, for example in the gRNA sequence (one paired strand underlined, one bolded):

NNNNNNNNNNNNNNNNNNNNGUUUUAGAGCUAUGCUGUUUUGGAAACAAAACAG CAUAGCAAGUUAAAAUAAGGCUAGUCCGUUAUCAACUUGAAAAAGUGGCACCGA GUCGGUGC (SEQ ID NO: 29).

In some embodiments, nucleotides are exchanged to remove poly-U tracts, for example in the gRNA sequences (exchanged nucleotides underlined):

NNNNNNNNNNNNNNNNNNNNGUAUUAGAGCUAGAAAUAGCAAGUUAAUAUAAGG CUAGUCCGUUAUCAACUUGAAAAAGUGGCACCGAGUCGGUGC (SEQ ID NO: 30);

NNNNNNNNNNNNNNNNNNNNGUUUAAGAGCUAGAAAUAGCAAGUUUAAAUAAGG CUAGUCCGUUAUCAACUUGAAAAAGUGGCACCGAGUCGGUGC (SEQ ID NO: 31); or NNNNNNNNNNNNNNNNNNNNGUAUUAGAGCUAUGCUGUAUUGGAAACAAUACAG CAUAGCAAGUUAAUAUAAGGCUAGUCCGUUAUCAACUUGAAAAAGUGGCACCGA GUCGGUGC (SEQ ID NO: 32).

The 5' Extension Domain

In an embodiment, a modular gRNA can comprise additional sequence, 5' to the second complementarity domain. In an embodiment, the 5' extension domain is 2 to 10, 2 to 9, 2 to 8, 2 to 7, 2 to 6, 2 to 5, or 2 to 4 nucleotides in length. In an embodiment, the 5' extension domain is 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more nucleotides in length.

In an embodiment, the 5' extension domain nucleotides do not comprise modifications, e.g., modifications of the type provided in Section VIII. However, in an embodiment, the 5' extension domain comprises one or more modifications, e.g., modifications that it render it less susceptible to degradation or more bio-compatible, e.g., less immunogenic. By way of example, the backbone of the 5' extension domain can be modified with a phosphorothioate, or other modification(s) from Section VIII. In an embodiment, a nucleotide of the 5' extension domain can comprise a 2' modification, e.g., a 2-acetylation, e.g., a 2' methylation, or other

modification(s) from Section VIII.

In an embodiment, the 5' extension domain can comprise as many as 1, 2, 3, 4, 5, 6, 7 or

8 modifications. In an embodiment, the 5' extension domain comprises as many as 1, 2, 3, or 4

105

5535.1 modifications within 5 nucleotides of its 5' end, e.g., in a modular gRNA molecule. In an embodiment, the 5' extension domain comprises as many as 1, 2, 3, or 4 modifications within 5 nucleotides of its 3' end, e.g., in a modular gRNA molecule.

In an embodiment, the 5' extension domain comprises modifications at two consecutive nucleotides, e.g., two consecutive nucleotides that are within 5 nucleotides of the 5' end of the 5' extension domain, within 5 nucleotides of the 3' end of the 5' extension domain, or more than 5 nucleotides away from one or both ends of the 5' extension domain. In an embodiment, no two consecutive nucleotides are modified within 5 nucleotides of the 5' end of the 5' extension domain, within 5 nucleotides of the 3' end of the 5' extension domain, or within a region that is more than 5 nucleotides away from one or both ends of the 5' extension domain. In an embodiment, no nucleotide is modified within 5 nucleotides of the 5' end of the 5' extension domain, within 5 nucleotides of the 3' end of the 5' extension domain, or within a region that is more than 5 nucleotides away from one or both ends of the 5' extension domain.

Modifications in the 5' extension domain can be selected so as to not interfere with gRNA molecule efficacy, which can be evaluated by testing a candidate modification in the system described in Section IV. gRNAs having a candidate 5' extension domain having a selected length, sequence, degree of complementarity, or degree of modification, can be evaluated in the system described at Section IV. The candidate 5' extension domain can be placed, either alone, or with one or more other candidate changes in a gRNA molecule/Cas9 molecule system known to be functional with a selected target and evaluated.

In an embodiment, the 5' extension domain has at least 60, 70, 80, 85, 90 or 95% homology with, or differs by no more than 1, 2, 3, 4, 5, or 6 nucleotides from, a reference 5' extension domain, e.g., a naturally occurring, e.g., an S. pyogenes, or S. aureus S. thermophilus, 5' extension domain, or a 5' extension domain described herein, e.g., from Figs. 1A-1G.

The Linking Domain

In a unimolecular gRNA molecule the linking domain is disposed between the first and second complementarity domains. In a modular gRNA molecule, the two molecules are associated with one another by the complementarity domains.

In an embodiment, the linking domain is 10 +/-5, 20+/-5, 30+/-5, 40+/-5, 50+/-5, 60+/-5,

70+/-5, 80+/-5, 90+/-5, or 100+/-5 nucleotides, in length.

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5535.1 In an embodiment, the linking domain is 20+/- 10, 30+/- 10, 40+/- 10, 50+/- 10, 60+/- 10, 70+/- 10, 80+/- 10, 90+/- 10, or 100+/- 10 nucleotides, in length.

In an embodiment, the linking domain is 10 to 100, 10 to 90, 10 to 80, 10 to 70, 10 to 60, 10 to 50, 10 to 40, 10 to 30, 10 to 20 or 10 to 15 nucleotides in length. In other embodiments, the linking domain is 20 to 100, 20 to 90, 20 to 80, 20 to 70, 20 to 60, 20 to 50, 20 to 40, 20 to 30, or 20 to 25 nucleotides in length.

In an embodiment, the linking domain is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 17, 18, 19, or 20 nucleotides in length.

In an embodiment, the linking domain is a covalent bond.

In an embodiment, the linking domain comprises a duplexed region, typically adjacent to or within 1, 2, or 3 nucleotides of the 3' end of the first complementarity domain and/or the 5- end of the second complementarity domain. In an embodiment, the duplexed region can be 20+/-10 base pairs in length. In an embodiment, the duplexed region can be 10+/-5, 15+/-5, 20+/-5, or 30+/-5 base pairs in length. In an embodiment, the duplexed region can be 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 base pairs in length.

Typically the sequences forming the duplexed region have exact complementarity with one another, though in some embodiments as many as 1, 2, 3, 4, 5, 6, 7 or 8 nucleotides are not complementary with the corresponding nucleotides.

In an embodiment, the linking domain nucleotides do not comprise modifications, e.g., modifications of the type provided in Section VIII. However, in an embodiment, the linking domain comprises one or more modifications, e.g., modifications that it render it less susceptible to degradation or more bio-compatible, e.g., less immunogenic. By way of example, the backbone of the linking domain can be modified with a phosphorothioate, or other

modification(s) from Section VIII. In an embodiment a nucleotide of the linking domain can comprise a 2' modification, e.g., a 2-acetylation, e.g., a 2' methylation, or other modification(s) from Section VIII. In some embodiments, the linking domain can comprise as many as 1, 2, 3, 4, 5, 6, 7 or 8 modifications.

Modifications in a linking domain can be selected so as to not interfere with targeting efficacy, which can be evaluated by testing a candidate modification in the system described in Section IV. gRNAs having a candidate linking domain having a selected length, sequence, degree of complementarity, or degree of modification, can be evaluated a system described in

107

5535.1 Section IV. A candidate linking domain can be placed, either alone, or with one or more other candidate changes in a gRNA molecule/Cas9 molecule system known to be functional with a selected target and evaluated.

In an embodiment, the linking domain has at least 60, 70, 80, 85, 90 or 95% homology with, or differs by no more than 1, 2, 3, 4, 5 ,or 6 nucleotides from, a reference linking domain, e.g., a linking domain described herein, e.g., from Figs. 1A-1G.

The Proximal Domain

In an embodiment, the proximal domain is 6 +1-2, 1+1-2, 8+/-2, 9+1-2, 10+/-2, 11+/-2, 12+/-2, 13+/-2, 14+/-2, 14+/-2, 16+/-2, 17+/-2, 18+/-2, 19+/-2, or 20+/-2 nucleotides in length.

In an embodiment, the proximal domain is 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or 26 nucleotides in length.

In an embodiment, the proximal domain is 5 to 20, 7, to 18, 9 to 16, or 10 to 14 nucleotides in length.

In an embodiment, the proximal domain nucleotides do not comprise modifications, e.g., modifications of the type provided in Section VIII. However, in an embodiment, the proximal domain comprises one or more modifications, e.g., modifications that it render it less susceptible to degradation or more bio-compatible, e.g., less immunogenic. By way of example, the backbone of the proximal domain can be modified with a phosphorothioate, or other

modification(s) from Section VIII. In an embodiment a nucleotide of the proximal domain can comprise a 2' modification, e.g., a 2-acetylation, e.g., a 2' methylation, or other modification(s) from Section VIII.

In an embodiment, the proximal domain can comprise as many as 1, 2, 3, 4, 5, 6, 7 or 8 modifications. In an embodiment, the proximal domain comprises as many as 1, 2, 3, or 4 modifications within 5 nucleotides of its 5' end, e.g., in a modular gRNA molecule. In an embodiment, the target domain comprises as many as 1, 2, 3, or 4 modifications within 5 nucleotides of its 3' end, e.g., in a modular gRNA molecule.

In an embodiment, the proximal domain comprises modifications at two consecutive nucleotides, e.g., two consecutive nucleotides that are within 5 nucleotides of the 5' end of the proximal domain, within 5 nucleotides of the 3' end of the proximal domain, or more than 5 nucleotides away from one or both ends of the proximal domain. In an embodiment, no two

108

5535.1 consecutive nucleotides are modified within 5 nucleotides of the 5' end of the proximal domain, within 5 nucleotides of the 3' end of the proximal domain, or within a region that is more than 5 nucleotides away from one or both ends of the proximal domain. In an embodiment, no nucleotide is modified within 5 nucleotides of the 5' end of the proximal domain, within 5 nucleotides of the 3' end of the proximal domain, or within a region that is more than 5 nucleotides away from one or both ends of the proximal domain.

Modifications in the proximal domain can be selected so as to not interfere with gRNA molecule efficacy, which can be evaluated by testing a candidate modification in the system described in Section IV. gRNAs having a candidate proximal domain having a selected length, sequence, degree of complementarity, or degree of modification, can be evaluated in the system described at Section IV. The candidate proximal domain can be placed, either alone, or with one or more other candidate changes in a gRNA molecule/Cas9 molecule system known to be functional with a selected target and evaluated.

In an embodiment, the proximal domain has at least 60, 70, 80, 85 90 or 95% homology with, or differs by no more than 1, 2, 3, 4, 5 , or 6 nucleotides from, a reference proximal domain, e.g., a naturally occurring, e.g., an S. pyogenes, S. aureus or S. thermophilus, proximal domain, or a proximal domain described herein, e.g., from Figs. 1A-1G.

The Tail Domain

In an embodiment, the tail domain is 10 +/-5, 20+/-5, 30+/-5, 40+/-5, 50+/-5, 60+/-5,

70+/-5, 80+/-5, 90+/-5, or 100+/-5 nucleotides, in length.

In an embodiment, the tail domain is 20+/-5 nucleotides in length.

In an embodiment, the tail domain is 20+/- 10, 30+/- 10, 40+/- 10, 50+/- 10, 60+/- 10, 70+/- 10, 80+/- 10, 90+/- 10, or 100+/- 10 nucleotides, in length.

In an embodiment, the tail domain is 25+/- 10 nucleotides in length.

In an embodiment, the tail domain is 10 to 100, 10 to 90, 10 to 80, 10 to 70, 10 to 60, 10 to 50, 10 to 40, 10 to 30, 10 to 20 or 10 to 15 nucleotides in length.

In other embodiments, the tail domain is 20 to 100, 20 to 90, 20 to 80, 20 to 70, 20 to 60, 20 to 50, 20 to 40, 20 to 30, or 20 to 25 nucleotides in length.

In an embodiment, the tail domain is 1 to 20, 1 to 15, 1 to 10, or 1 to 5 nucleotides in length.

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5535.1 In an embodiment, the tail domain nucleotides do not comprise modifications, e.g., modifications of the type provided in Section VIII. However, in an embodiment, the tail domain comprises one or more modifications, e.g., modifications that it render it less susceptible to degradation or more bio-compatible, e.g., less immunogenic. By way of example, the backbone of the tail domain can be modified with a phosphorothioate, or other modification(s) from

Section VIII. In an embodiment a nucleotide of the tail domain can comprise a 2' modification, e.g., a 2-acetylation, e.g., a 2' methylation, or other modification(s) from Section VIII.

In some embodiments, the tail domain can have as many as 1, 2, 3, 4, 5, 6, 7 or 8 modifications. In an embodiment, the target domain comprises as many as 1, 2, 3, or 4 modifications within 5 nucleotides of its 5' end. In an embodiment, the target domain comprises as many as 1, 2, 3, or 4 modifications within 5 nucleotides of its 3' end.

In an embodiment, the tail domain comprises a tail duplex domain, which can form a tail duplexed region. In an embodiment, the tail duplexed region can be 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 base pairs in length. In an embodiment, a further single stranded domain, exists 3' to the tail duplexed domain. In an embodiment, this domain is 3, 4, 5, 6, 7, 8, 9, or 10 nucleotides in length. In an embodiment it is 4 to 6 nucleotides in length.

In an embodiment, the tail domain has at least 60, 70, 80, or 90% homology with, or differs by no more than 1, 2, 3, 4, 5 ,or 6 nucleotides from, a reference tail domain, e.g., a naturally occurring, e.g., an S. pyogenes, S. aureus or S. thermophilus, tail domain, or a tail domain described herein, e.g., from Figs. 1A-1G.

In an embodiment, the proximal and tail domain, taken together, comprise the following sequences:

AAGGCUAGUCCGUUAUCAACUUGAAAAAGUGGCACCGAGUCGGUGCU (SEQ ID NO: 33), or

AAGGCUAGUCCGUUAUCAACUUGAAAAAGUGGCACCGAGUCGGUGGUGC (SEQ ID NO: 34), or

AAGGCUAGUCCGUUAUCAACUUGAAAAAGUGGCACCGAGUCGGUGCGGAUC (SEQ ID NO: 35), or

AAGGCUAGUCCGUUAUCAACUUGAAAAAGUG (SEQ ID NO: 36), or

AAGGCUAGUCCGUUAUCA (SEQ ID NO: 37), or

AAGGCUAGUCCG (SEQ ID NO: 38).

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5535.1 In an embodiment, the tail domain comprises the 3' sequence UUUUUU, e.g., if a U6 promoter is used for transcription.

In an embodiment, the tail domain comprises the 3' sequence UUUU, e.g., if an HI promoter is used for transcription.

In an embodiment, tail domain comprises variable numbers of 3' Us depending, e.g., on the termination signal of the pol-III promoter used.

In an embodiment, the tail domain comprises variable 3' sequence derived from the DNA template if a T7 promoter is used.

In an embodiment, the tail domain comprises variable 3' sequence derived from the DNA template, e.g., if in vitro transcription is used to generate the RNA molecule.

In an embodiment, the tail domain comprises variable 3' sequence derived from the DNA template, e., if a pol-II promoter is used to drive transcription.

Modifications in the tail domain can be selected so as to not interfere with targeting efficacy, which can be evaluated by testing a candidate modification in the system described in Section IV. gRNAs having a candidate tail domain having a selected length, sequence, degree of complementarity, or degree of modification, can be evaluated in the system described in Section IV. The candidate tail domain can be placed, either alone, or with one or more other candidate changes in a gRNA molecule/Cas9 molecule system known to be functional with a selected target and evaluated.

In an embodiment, the tail domain comprises modifications at two consecutive nucleotides, e.g., two consecutive nucleotides that are within 5 nucleotides of the 5' end of the tail domain, within 5 nucleotides of the 3' end of the tail domain, or more than 5 nucleotides away from one or both ends of the tail domain. In an embodiment, no two consecutive nucleotides are modified within 5 nucleotides of the 5' end of the tail domain, within 5 nucleotides of the 3' end of the tail domain, or within a region that is more than 5 nucleotides away from one or both ends of the tail domain. In an embodiment, no nucleotide is modified within 5 nucleotides of the 5' end of the tail domain, within 5 nucleotides of the 3' end of the tail domain, or within a region that is more than 5 nucleotides away from one or both ends of the tail domain.

In an embodiment a gRNA has the following structure:

111

5535.1 5' [targeting domain] -[first complementarity domain] -[linking domain] -[second complementarity domain] -[proximal domain] -[tail domain] -3'

wherein, the targeting domain comprises a core domain and optionally a secondary domain, and is 10 to 50 nucleotides in length;

the first complementarity domain is 5 to 25 nucleotides in length and, In an embodiment has at least 50, 60, 70, 80, 85, 90 or 95% homology with a reference first complementarity domain disclosed herein;

the linking domain is 1 to 5 nucleotides in length;

the second complementarity domain is 5 to 27 nucleotides in length and, in an embodiment has at least 50, 60, 70, 80, 85, 90 or 95% homology with a reference second complementarity domain disclosed herein;

the proximal domain is 5 to 20 nucleotides in length and, in an embodiment has at least 50, 60, 70, 80, 85, 90 or 95% homology with a reference proximal domain disclosed herein; and the tail domain is absent or a nucleotide sequence is 1 to 50 nucleotides in length and, in an embodiment has at least 50, 60, 70, 80, 85, 90 or 95% homology with a reference tail domain disclosed herein.

Exemplary Chimeric gRNAs

In an embodiment, a unimolecular, or chimeric, gRNA comprises, preferably from 5' to a targeting domain (which is complementary to a target nucleic acid);

a first complementarity domain, e.g., comprising 15, 16, 17, 18, 19, 20, 21, 22,

23, 24, 25, or 26 nucleotides;

a linking domain;

a second complementarity domain (which is complementary to the first complementarity domain);

a proximal domain; and

a tail domain,

wherein,

(a) the proximal and tail domain, when taken together, comprise at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides;

112

5535.1 (b) there are at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides 3' to the last nucleotide of the second complementarity domain; or

(c) there are at least 16, 19, 21, 26, 31, 32, 36, 41, 46, 50, 51, or 54 nucleotides 3' to the last nucleotide of the second complementarity domain that is complementary to its corresponding nucleotide of the first complementarity domain.

In an embodiment, the sequence from (a), (b), or (c), has at least 60, 75, 80, 85, 90, 95, or 99% homology with the corresponding sequence of a naturally occurring gRNA, or with a gRNA described herein.

In an embodiment, the proximal and tail domain, when taken together, comprise at least

15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides.

In an embodiment, there are at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides 3' to the last nucleotide of the second complementarity domain.

In an embodiment, there are at least 16, 19, 21, 26, 31, 32, 36, 41, 46, 50, 51, or 54 nucleotides 3' to the last nucleotide of the second complementarity domain that is

complementary to its corresponding nucleotide of the first complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or 26 nucleotides (e.g., 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or 26 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or 26 nucleotides in length.

In an embodiment, the targeting domain comprises, has, or consists of, 16 nucleotides (e.g., 16 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 16 nucleotides in length.

In an embodiment, the targeting domain comprises, has, or consists of, 17 nucleotides (e.g., 17 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 17 nucleotides in length.

In an embodiment, the targeting domain comprises, has, or consists of, 18 nucleotides (e.g., 18 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 18 nucleotides in length.

113

5535.1 In an embodiment, the targeting domain comprises, has, or consists of, 19 nucleotides (e.g., 19 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 19 nucleotides in length.

In an embodiment, the targeting domain comprises, has, or consists of, 20 nucleotides (e.g., 20 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 20 nucleotides in length.

In an embodiment, the targeting domain comprises, has, or consists of, 21 nucleotides (e.g., 21 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 21 nucleotides in length.

In an embodiment, the targeting domain comprises, has, or consists of, 22 nucleotides

(e.g., 22 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 22 nucleotides in length.

In an embodiment, the targeting domain comprises, has, or consists of, 23 nucleotides (e.g., 23 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 23 nucleotides in length.

In an embodiment, the targeting domain comprises, has, or consists of, 24 nucleotides (e.g., 24 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 24 nucleotides in length.

In an embodiment, the targeting domain comprises, has, or consists of, 25 nucleotides (e.g., 25 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 25 nucleotides in length.

In an embodiment, the targeting domain comprises, has, or consists of, 26 nucleotides (e.g., 26 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 26 nucleotides in length.

In an embodiment, the targeting domain comprises, has, or consists of, 16 nucleotides

(e.g., 16 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 16 nucleotides in length; and the proximal and tail domain, when taken together, comprise at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides.

In an embodiment, the targeting domain comprises, has, or consists of, 16 nucleotides (e.g., 16 consecutive nucleotides) having complementarity with the target domain, e.g., the

114

5535.1 targeting domain is 16 nucleotides in length; and there are at least 15, 18, 20, 25, 30, 31, 35, 40,

45, 49, 50, or 53 nucleotides 3' to the last nucleotide of the second complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 16 nucleotides (e.g., 16 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 16 nucleotides in length; and there are at least 16, 19, 21, 26, 31, 32, 36, 41,

46, 50, 51, or 54 nucleotides 3' to the last nucleotide of the second complementarity domain that is complementary to its corresponding nucleotide of the first complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 17 nucleotides (e.g., 17 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 17 nucleotides in length; and the proximal and tail domain, when taken together, comprise at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides.

In an embodiment, the targeting domain comprises, has, or consists of, 17 nucleotides (e.g., 17 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 17 nucleotides in length; and there are at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides 3' to the last nucleotide of the second complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 17 nucleotides (e.g., 17 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 17 nucleotides in length; and there are at least 16, 19, 21, 26, 31, 32, 36, 41, 46, 50, 51, or 54 nucleotides 3' to the last nucleotide of the second complementarity domain that is complementary to its corresponding nucleotide of the first complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 18 nucleotides (e.g., 18 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 18 nucleotides in length; and the proximal and tail domain, when taken together, comprise at leastl5, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides.

In an embodiment, the targeting domain comprises, has, or consists of, 18 nucleotides

(e.g., 18 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 18 nucleotides in length; and there are at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides 3' to the last nucleotide of the second complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 18 nucleotides (e.g., 18 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 18 nucleotides in length; and there are at least 16, 19, 21, 26, 31, 32, 36, 41,

115

5535.1 46, 50, 51, or 54 nucleotides 3' to the last nucleotide of the second complementarity domain that is complementary to its corresponding nucleotide of the first complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 19 nucleotides (e.g., 19 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 19 nucleotides in length; and the proximal and tail domain, when taken together, comprise at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides.

In an embodiment, the targeting domain comprises, has, or consists of, 19 nucleotides (e.g., 19 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 19 nucleotides in length; and there are at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides 3' to the last nucleotide of the second complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 19 nucleotides (e.g., 19 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 19 nucleotides in length; and there are at least 16, 19, 21, 26, 31, 32, 36, 41, 46, 50, 51, or 54 nucleotides 3' to the last nucleotide of the second complementarity domain that is complementary to its corresponding nucleotide of the first complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 20 nucleotides (e.g., 20 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 20 nucleotides in length; and the proximal and tail domain, when taken together, comprise at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides.

In an embodiment, the targeting domain comprises, has, or consists of, 20 nucleotides

(e.g., 20 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 20 nucleotides in length; and there are at least 15, 18, 20, 25, 30, 31, 35, 40,

45, 49, 50, or 53 nucleotides 3' to the last nucleotide of the second complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 20 nucleotides (e.g., 20 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 20 nucleotides in length; and there are at least 16, 19, 21, 26, 31, 32, 36, 41,

46, 50, 51, or 54 nucleotides 3' to the last nucleotide of the second complementarity domain that is complementary to its corresponding nucleotide of the first complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 21 nucleotides (e.g., 21 consecutive nucleotides) having complementarity with the target domain, e.g., the

116

5535.1 targeting domain is 21 nucleotides in length; and the proximal and tail domain, when taken together, comprise at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides.

In an embodiment, the targeting domain comprises, has, or consists of, 21 nucleotides (e.g., 21 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 21 nucleotides in length; and there are at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides 3' to the last nucleotide of the second complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 21 nucleotides (e.g., 21 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 21 nucleotides in length; and there are at least 16, 19, 21, 26, 31, 32, 36, 41, 46, 50, 51, or 54 nucleotides 3' to the last nucleotide of the second complementarity domain that is complementary to its corresponding nucleotide of the first complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 22 nucleotides (e.g., 22 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 22 nucleotides in length; and the proximal and tail domain, when taken together, comprise at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides.

In an embodiment, the targeting domain comprises, has, or consists of, 22 nucleotides (e.g., 22 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 22 nucleotides in length; and there are at least 15, 18, 20, 25, 30, 31, 35, 40,

45, 49, 50, or 53 nucleotides 3' to the last nucleotide of the second complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 22 nucleotides

(e.g., 22 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 22 nucleotides in length; and there are at least 16, 19, 21, 26, 31, 32, 36, 41,

46, 50, 51, or 54 nucleotides 3' to the last nucleotide of the second complementarity domain that is complementary to its corresponding nucleotide of the first complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 23 nucleotides

(e.g., 23 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 23 nucleotides in length; and the proximal and tail domain, when taken together, comprise at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides.

In an embodiment, the targeting domain comprises, has, or consists of, 23 nucleotides (e.g., 23 consecutive nucleotides) having complementarity with the target domain, e.g., the

117

5535.1 targeting domain is 23 nucleotides in length; and there are at least 15, 18, 20, 25, 30, 31, 35, 40,

45, 49, 50, or 53 nucleotides 3' to the last nucleotide of the second complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 23 nucleotides (e.g., 23 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 23 nucleotides in length; and there are at least 16, 19, 21, 26, 31, 32, 36, 41,

46, 50, 51, or 54 nucleotides 3' to the last nucleotide of the second complementarity domain that is complementary to its corresponding nucleotide of the first complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 24 nucleotides (e.g., 24 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 24 nucleotides in length; and the proximal and tail domain, when taken together, comprise at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides.

In an embodiment, the targeting domain comprises, has, or consists of, 24 nucleotides (e.g., 24 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 24 nucleotides in length; and there are at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides 3' to the last nucleotide of the second complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 24 nucleotides (e.g., 24 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 24 nucleotides in length; and there are at least 16, 19, 21, 26, 31, 32, 36, 41, 46, 50, 51, or 54 nucleotides 3' to the last nucleotide of the second complementarity domain that is complementary to its corresponding nucleotide of the first complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 25 nucleotides (e.g., 25 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 25 nucleotides in length; and the proximal and tail domain, when taken together, comprise at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides.

In an embodiment, the targeting domain comprises, has, or consists of, 25 nucleotides

(e.g., 25 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 25 nucleotides in length; and there are at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides 3' to the last nucleotide of the second complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 25 nucleotides (e.g., 25 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 25 nucleotides in length; and there are at least 16, 19, 21, 26, 31, 32, 36, 41,

118

5535.1 46, 50, 51, or 54 nucleotides 3' to the last nucleotide of the second complementarity domain that is complementary to its corresponding nucleotide of the first complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 26 nucleotides (e.g., 26 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 26 nucleotides in length; and the proximal and tail domain, when taken together, comprise at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides.

In an embodiment, the targeting domain comprises, has, or consists of, 26 nucleotides (e.g., 26 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 26 nucleotides in length; and there are at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides 3' to the last nucleotide of the second complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 26 nucleotides (e.g., 26 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 26 nucleotides in length; and there are at least 16, 19, 21, 26, 31, 32, 36, 41, 46, 50, 51, or 54 nucleotides 3' to the last nucleotide of the second complementarity domain that is complementary to its corresponding nucleotide of the first complementarity domain.

In an embodiment, the unimolecular, or chimeric, gRNA molecule (comprising a targeting domain, a first complementary domain, a linking domain, a second complementary domain, a proximal domain and, optionally, a tail domain) comprises the following sequence in which the targeting domain is depicted as 20 Ns but could be any sequence and range in length from 16 to 26 nucleotides and in which the gRNA sequence is followed by 6 Us, which serve as a termination signal for the U6 promoter, but which could be either absent or fewer in number: NNNNNNNNNNNNNNNNNNNNGUUUUAGAGCUAGAAAUAGCAAGUUAAAAUAAGG CUAGUCCGUUAUCAACUUGAAAAAGUGGCACCGAGUCGGUGCUUUUUU (SEQ ID NO: 45). In an embodiment, the unimolecular, or chimeric, gRNA molecule is a S. pyogenes gRNA molecule.

In some embodiments, the unimolecular, or chimeric, gRNA molecule (comprising a targeting domain, a first complementary domain, a linking domain, a second complementary domain, a proximal domain and, optionally, a tail domain) comprises the following sequence in which the targeting domain is depicted as 20 Ns but could be any sequence and range in length from 16 to 26 nucleotides and in which the gRNA sequence is followed by 6 Us, which serve as a termination signal for the U6 promoter, but which could be either absent or fewer in number:

119

5535.1 NNNNNNNNNNNNNNNNNNNNGUUUUAGUACUCUGGAAACAGAAUCUACUAAAAC AAGGCAAAAUGCCGUGUUUAUCUCGUCAACUUGUUGGCGAGAUUUUUU (SEQ ID NO: 40). In an embodiment, the unimolecular, or chimeric, gRNA molecule is a S. aureus gRNA molecule.

Exemplary Modular gRNAs

In an embodiment, a modular gRNA comprises:

a first strand comprising, preferably from 5' to 3' ;

a targeting domain, e.g., comprising 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, or 26 nucleotides;

a first complementarity domain; and

a second strand, comprising, preferably from 5' to 3':

optionally a 5' extension domain;

a second complementarity domain;

a proximal domain; and

a tail domain,

wherein:

(a) the proximal and tail domain, when taken together, comprise

at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides; (b) there are at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides 3' to the last nucleotide of the second complementarity domain; or

(c) there are at least 16, 19, 21, 26, 31, 32, 36, 41, 46, 50, 51, or 54 nucleotides 3' to the last nucleotide of the second complementarity domain that is complementary to its corresponding nucleotide of the first complementarity domain.

In an embodiment, the sequence from (a), (b), or (c), has at least 60, 75, 80, 85, 90, 95, or 99% homology with the corresponding sequence of a naturally occurring gRNA, or with a gRNA described herein.

In an embodiment, the proximal and tail domain, when taken together, comprise at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides.

120

5535.1 In an embodiment, there are at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides 3' to the last nucleotide of the second complementarity domain.

In an embodiment, there are at least 16, 19, 21, 26, 31, 32, 36, 41, 46, 50, 51, or 54 nucleotides 3' to the last nucleotide of the second complementarity domain that is

complementary to its corresponding nucleotide of the first complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or 26 nucleotides (e.g., 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or 26 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or 26 nucleotides in length.

In an embodiment, the targeting domain comprises, has, or consists of, 16 nucleotides

(e.g., 16 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 16 nucleotides in length.

In an embodiment, the targeting domain comprises, has, or consists of, 17 nucleotides (e.g., 17 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 17 nucleotides in length.

In an embodiment, the targeting domain comprises, has, or consists of, 18 nucleotides (e.g., 18 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 18 nucleotides in length.

In an embodiment, the targeting domain comprises, has, or consists of, 19 nucleotides (e.g., 19 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 19 nucleotides in length.

In an embodiment, the targeting domain comprises, has, or consists of, 20 nucleotides (e.g., 20 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 20 nucleotides in length.

In an embodiment, the targeting domain comprises, has, or consists of, 21 nucleotides

(e.g., 21 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 21 nucleotides in length.

In an embodiment, the targeting domain comprises, has, or consists of, 22 nucleotides (e.g., 22 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 22 nucleotides in length.

121

5535.1 In an embodiment, the targeting domain comprises, has, or consists of, 23 nucleotides (e.g., 23 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 23 nucleotides in length.

In an embodiment, the targeting domain comprises, has, or consists of, 24 nucleotides (e.g., 24 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 24 nucleotides in length.

In an embodiment, the targeting domain comprises, has, or consists of, 25 nucleotides (e.g., 25 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 25 nucleotides in length.

In an embodiment, the targeting domain comprises, has, or consists of, 26 nucleotides

(e.g., 26 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 26 nucleotides in length.

In an embodiment, the targeting domain comprises, has, or consists of, 16 nucleotides (e.g., 16 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 16 nucleotides in length; and the proximal and tail domain, when taken together, comprise at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides.

In an embodiment, the targeting domain comprises, has, or consists of, 16 nucleotides (e.g., 16 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 16 nucleotides in length; and there are at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides 3' to the last nucleotide of the second complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 16 nucleotides (e.g., 16 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 16 nucleotides in length; and there are at least 16, 19, 21, 26, 31, 32, 36, 41, 46, 50, 51, or 54 nucleotides 3' to the last nucleotide of the second complementarity domain that is complementary to its corresponding nucleotide of the first complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 17 nucleotides (e.g., 17 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 17 nucleotides in length; and the proximal and tail domain, when taken together, comprise at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides.

In an embodiment, the targeting domain comprises, has, or consists of, 17 nucleotides

(e.g., 17 consecutive nucleotides) having complementarity with the target domain, e.g., the

122

5535.1 targeting domain is 17 nucleotides in length; and there are at least 15, 18, 20, 25, 30, 31, 35, 40,

45, 49, 50, or 53 nucleotides 3' to the last nucleotide of the second complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 17 nucleotides (e.g., 17 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 17 nucleotides in length; and there are at least 16, 19, 21, 26, 31, 32, 36, 41,

46, 50, 51, or 54 nucleotides 3' to the last nucleotide of the second complementarity domain that is complementary to its corresponding nucleotide of the first complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 18 nucleotides (e.g., 18 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 18 nucleotides in length; and the proximal and tail domain, when taken together, comprise at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides.

In an embodiment, the targeting domain comprises, has, or consists of, 18 nucleotides (e.g., 18 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 18 nucleotides in length; and there are at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides 3' to the last nucleotide of the second complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 18 nucleotides (e.g., 18 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 18 nucleotides in length; and there are at least 16, 19, 21, 26, 31, 32, 36, 41, 46, 50, 51, or 54 nucleotides 3' to the last nucleotide of the second complementarity domain that is complementary to its corresponding nucleotide of the first complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 19 nucleotides (e.g., 19 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 19 nucleotides in length; and the proximal and tail domain, when taken together, comprise at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides.

In an embodiment, the targeting domain comprises, has, or consists of, 19 nucleotides

(e.g., 19 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 19 nucleotides in length; and there are at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides 3' to the last nucleotide of the second complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 19 nucleotides (e.g., 19 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 19 nucleotides in length; and there are at least 16, 19, 21, 26, 31, 32, 36, 41,

123

5535.1 46, 50, 51, or 54 nucleotides 3' to the last nucleotide of the second complementarity domain that is complementary to its corresponding nucleotide of the first complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 20 nucleotides (e.g., 20 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 20 nucleotides in length; and the proximal and tail domain, when taken together, comprise at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides.

In an embodiment, the targeting domain comprises, has, or consists of, 20 nucleotides (e.g., 20 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 20 nucleotides in length; and there are at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides 3' to the last nucleotide of the second complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 20 nucleotides (e.g., 20 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 20 nucleotides in length; and there are at least 16, 19, 21, 26, 31, 32, 36, 41, 46, 50, 51, or 54 nucleotides 3' to the last nucleotide of the second complementarity domain that is complementary to its corresponding nucleotide of the first complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 21 nucleotides (e.g., 21 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 21 nucleotides in length; and the proximal and tail domain, when taken together, comprise at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides.

In an embodiment, the targeting domain comprises, has, or consists of, 21 nucleotides

(e.g., 21 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 21 nucleotides in length; and there are at least 15, 18, 20, 25, 30, 31, 35, 40,

45, 49, 50, or 53 nucleotides 3' to the last nucleotide of the second complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 21 nucleotides (e.g., 21 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 21 nucleotides in length; and there are at least 16, 19, 21, 26, 31, 32, 36, 41,

46, 50, 51, or 54 nucleotides 3' to the last nucleotide of the second complementarity domain that is complementary to its corresponding nucleotide of the first complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 22 nucleotides (e.g., 22 consecutive nucleotides) having complementarity with the target domain, e.g., the

124

5535.1 targeting domain is 22 nucleotides in length; and the proximal and tail domain, when taken together, comprise at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides.

In an embodiment, the targeting domain comprises, has, or consists of, 22 nucleotides (e.g., 22 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 22 nucleotides in length; and there are at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides 3' to the last nucleotide of the second complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 22 nucleotides (e.g., 22 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 22 nucleotides in length; and there are at least 16, 19, 21, 26, 31, 32, 36, 41, 46, 50, 51, or 54 nucleotides 3' to the last nucleotide of the second complementarity domain that is complementary to its corresponding nucleotide of the first complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 23 nucleotides (e.g., 23 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 23 nucleotides in length; and the proximal and tail domain, when taken together, comprise at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides.

In an embodiment, the targeting domain comprises, has, or consists of, 23 nucleotides (e.g., 23 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 23 nucleotides in length; and there are at least 15, 18, 20, 25, 30, 31, 35, 40,

45, 49, 50, or 53 nucleotides 3' to the last nucleotide of the second complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 23 nucleotides

(e.g., 23 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 23 nucleotides in length; and there are at least 16, 19, 21, 26, 31, 32, 36, 41,

46, 50, 51, or 54 nucleotides 3' to the last nucleotide of the second complementarity domain that is complementary to its corresponding nucleotide of the first complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 24 nucleotides

(e.g., 24 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 24 nucleotides in length; and the proximal and tail domain, when taken together, comprise at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides.

In an embodiment, the targeting domain comprises, has, or consists of, 24 nucleotides (e.g., 24 consecutive nucleotides) having complementarity with the target domain, e.g., the

125

5535.1 targeting domain is 24 nucleotides in length; and there are at least 15, 18, 20, 25, 30, 31, 35, 40,

45, 49, 50, or 53 nucleotides 3' to the last nucleotide of the second complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 24 nucleotides (e.g., 24 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 24 nucleotides in length; and there are at least 16, 19, 21, 26, 31, 32, 36, 41,

46, 50, 51, or 54 nucleotides 3' to the last nucleotide of the second complementarity domain that is complementary to its corresponding nucleotide of the first complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 25 nucleotides (e.g., 25 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 25 nucleotides in length; and the proximal and tail domain, when taken together, comprise at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides.

In an embodiment, the targeting domain comprises, has, or consists of, 25 nucleotides (e.g., 25 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 25 nucleotides in length; and there are at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides 3' to the last nucleotide of the second complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 25 nucleotides (e.g., 25 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 25 nucleotides in length; and there are at least 16, 19, 21, 26, 31, 32, 36, 41, 46, 50, 51, or 54 nucleotides 3' to the last nucleotide of the second complementarity domain that is complementary to its corresponding nucleotide of the first complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 26 nucleotides (e.g., 26 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 26 nucleotides in length; and the proximal and tail domain, when taken together, comprise at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides.

In an embodiment, the targeting domain comprises, has, or consists of, 26 nucleotides

(e.g., 26 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 26 nucleotides in length; and there are at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides 3' to the last nucleotide of the second complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 26 nucleotides (e.g., 26 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 26 nucleotides in length; and there are at least 16, 19, 21, 26, 31, 32, 36, 41,

126

5535.1 46, 50, 51, or 54 nucleotides 3' to the last nucleotide of the second complementarity domain that is complementary to its corresponding nucleotide of the first complementarity domain.

II. Methods for Designing gRNAs

Methods for designing gRNAs are described herein, including methods for selecting, designing and validating target domains. Exemplary targeting domains are also provided herein. Targeting Domains discussed herein can be incorporated into the gRNAs described herein.

Methods for selection and validation of target sequences as well as off-target analyses are described, e.g., in Mali et al., 2013 SCIENCE 339(6121): 823-826; Hsu et al. NAT BIOTECHNOL, 31(9): 827-32; Fu et al., 2014 NAT BIOTECHNOL, doi: 10.1038/nbt.2808. PubMed PMID:

24463574; Heigwer et al., 2014 NAT METHODS l l(2): 122-3. doi: 10.1038/nmeth.2812. PubMed PMID: 24481216; Bae et al., 2014 BIOINFO MATICS PubMed PMID: 24463181; Xiao A et al., 2014 BIOINFORMATICS PubMed PMID: 24389662.

For example, a software tool can be used to optimize the choice of gRNA within a user' s target sequence, e.g., to minimize total off-target activity across the genome. Off target activity may be other than cleavage. For each possible gRNA choice using S. pyogenes Cas9, the tool can identify all off-target sequences (preceding either NAG or NGG PAMs) across the genome that contain up to certain number (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10) of mismatched base-pairs. The cleavage efficiency at each off-target sequence can be predicted, e.g., using an

experimentally-derived weighting scheme. Each possible gRNA is then ranked according to its total predicted off-target cleavage; the top-ranked gRNAs represent those that are likely to have the greatest on-target and the least off-target cleavage. Other functions, e.g., automated reagent design for CRISPR construction, primer design for the on-target Surveyor assay, and primer design for high-throughput detection and quantification of off-target cleavage via next-gen sequencing, can also be included in the tool. Candidate gRNA molecules can be evaluated by art-known methods or as described in Section IV herein.

The Targeting Domains discussed herein can be incorporated into the gRNAs described herein.

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5535.1 Strategies to identify gRNAs for S. pyogenes, S. Aureus, and N. meningitidis to knock out the SCNN1A gene

As an example, three strategies were utilized to identify gRNAs for use with S. pyogenes, S. aureus and N. meningitidis Cas9 enzymes.

In the first strategy, guide RNAs (gRNAs) for use with the S. pyogenes Cas9 (Tables 3A-

3C) were identified using the publically available web-based ZiFiT server (Fu et al., Improving CRISPR-Cas nuclease specificity using truncated guide RNAs. Nat Biotechnol. 2014 Jan 26. doi: 10.1038/nbt.2808. PubMed PMID: 24463574, for the original references see Sander et al., 2007, NAR 35:W599-605; Sander et al., 2010, NAR 38: W462-8). In addition to identifying potential gRNA sites adjacent to PAM sequences, the software also identifies all PAM adjacent sequences that differ by 1, 2, 3 or more nucleotides from the selected gRNA sites. Genomic DNA sequence for each gene was obtained from the UCSC Genome browser and sequences were screened for repeat elements using the publically available Repeat-Masker program. RepeatMmasker searches input DNA sequences for repeated elements and regions of low complexity. The output is a detailed annotation of the repeats present in a given query sequence. Following

identification, gRNAs for use with a S. pyogenes Cas9 were ranked into 3 or 4 tiers, as described below.

The gRNAs in tier 1 were selected based on their distance to the target site and their orthogonality in the genome (based on the ZiFiT identification of close matches in the human genome containing an NGG PAM). As an example, for all targets, both 17-mer and 20-mer gRNAs were designed. gRNAs were also selected both for single-gRNA nuclease cutting and for the dual gRNA nickase strategy. Criteria for selecting gRNAs and the determination for which gRNAs can be used for which strategy is based on several considerations:

1. For the dual nickase strategy, gRNA pairs should be oriented on the DNA such that PAMs are facing out and cutting with the D10A Cas9 nickase will result in 5' overhangs.

2. An assumption that cleaving with dual nickase pairs will result in deletion of the

entire intervening sequence at a reasonable frequency. However, it will also often result in indel mutations at the site of only one of the gRNAs. Candidate pair members can be tested for how efficiently they remove the entire sequence versus just causing indel mutations at the site of one gRNA.

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5535.1 While it can be desirable to have gRNAs start with a 5' G, this requirement was relaxed for some gRNAs in tier 1 in order to identify guides in the correct orientation, within a reasonable distance to the mutation and with a high level of orthogonality. In order to find a pair for the dual-nickase strategy it was necessary to either extend the distance from the mutation or remove the requirement for the 5'G. For selection of tier 2 gRNAs, the distance restriction was relaxed in some cases such that a longer sequence was scanned, but the 5'G was required for all gRNAs. Whether or not the distance requirement was relaxed depended on how many sites were found within the original search window. Tier 3 uses the same distance restriction as tier 2, but removes the requirement for a 5'G. Note that tiers are non-inclusive (each gRNA is listed only once).

As discussed above, gRNAs were identified for single-gRNA nuclease cleavage as well as for a dual-gRNA paired "nickase" strategy, as indicated.

gRNAs for use with the S. aureus (Tables 3D) Cas9s were identified manually by scanning genomic DNA sequence for the presence of PAM sequences. These gRNAs were not separated into tiers, but are provided in single lists for each species.

In a second strategy, Guide RNAs (gRNAs) for use with S. pyogenes, S. aureus and N. meningitidis Cas9s were identified using a DNA sequence searching algorithm. Guide RNA design was carried out using a custom guide RNA design software based on the public tool cas- offinder (reference:Cas-OFFinder: a fast and versatile algorithm that searches for potential off- target sites of Cas9 RNA-guided endonucleases., Bioinformatics. 2014 Feb 17. Bae S, Park J, Kim JS. PMID:24463181). Said custom guide RNA design software scores guides after calculating their genomewide off-target propensity. Typically matches ranging from perfect matches to 7 mismatches are considered for guides ranging in length from 17 to 24. Once the off- target sites are computationally determined , an aggregate score is calculated for each guide and summarized in a tabular output using a web-interface. In addition to identifying potential gRNA sites adjacent to PAM sequences, the software also identifies all PAM adjacent sequences that differ by 1, 2, 3 or more nucleotides from the selected gRNA sites. Genomic DNA sequence for each gene was obtained from the UCSC Genome browser and sequences were screened for repeat elements using the publically available RepeatMasker program. RepeatMasker searches

129

5535.1 input DNA sequences for repeated elements and regions of low complexity. The output is a detailed annotation of the repeats present in a given query sequence.

Following identification, gRNAs were ranked into tiers based on their distance to the target site, their orthogonality and presence of a 5' G (based on identification of close matches in the human genome containing a relavant PAM (e.g., in the case of S. pyogenes, a NGG PAM, in the case of S. aureus, a NNGRRT or NNGRRV PAM, and in the case of N. meningitidis, a NNNNGATT or NNNNGCTT PAM). Orthogonality refers to the number of sequences in the human genome that contain a minimum number of mismatches to the target sequence. A "high level of orthogonality" or "good orthogonality" may, for example, refer to 20-mer gRNAs that have no identical sequences in the human genome besides the intended target, nor any sequences that contain one or two mismatches in the target sequence. Targeting domains with good orthogonality are selected to minimize off-target DNA cleavage.

As an example, for S. pyogenes and N. meningitidis targets, 17-mer, or 20-mer gRNAs were designed. As another example, for S. aureus targets, 18-mer, 19-mer, 20-mer, 21-mer, 22- mer, 23-mer and 24-mer gRNAs were designed. Targeting domains, disclosed herein, may comprise the 17-mer described in Tables 43A-43E, 44A-44G or 45A-45E, e.g., the targeting domains of 18 or more nucleotides may comprise the 17-mer gRNAs described in Tables 43A- 43E, 44A-44G or 45A-45E. Targeting domains, disclosed herein, may comprises the 18-mer described in Tables 43A-43E, 44A-44G or 45A-45E, e.g., the targeting domains of 19 or more nucleotides may comprise the 18-mer gRNAs described in Tables 43A-43E, 44A-44G or 45A- 45E. Targeting domains, disclosed herein, may comprises the 19-mer described in Tables 43A- 43E, 44A-44G or 45A-45E, e.g., the targeting domains of 20 or more nucleotides may comprise the 19-mer gRNAs described in Tables 43A-43E, 44A-44G or 45A-45E. Targeting domains, disclosed herein, may comprises the 20-mer gRNAs described in Tables 43A-43E, 44A-44G or 45A-45E, e.g., the targeting domains of 21 or more nucleotides may comprise the 20-mer gRNAs described in Tables 43A-43E, 44A-44G or 45A-45E. Targeting domains, disclosed herein, may comprises the 21-mer described in Tables 43A-43E, 44A-44G or 45A-45E, e.g., the targeting domains of 22 or more nucleotides may comprise the 21-mer gRNAs described in

Tables 43A-43E, 44A-44G or 45A-45E. Targeting domains, disclosed herein, may comprises the 22-mer described in Tables 43A-43E, 44A-44G or 45A-45E, e.g., the targeting domains of 23 or more nucleotides may comprise the 22-mer gRNAs described in Tables 43A-43E, 44A-

130

5535.1 44G or 45A-45E. Targeting domains, disclosed herein, may comprises the 23-mer described in Tables 43A-43E, 44A-44G or 45A-45E,e.g., the targeting domains of 24 or more nucleotides may comprise the 23-mer gRNAs described in Tables 43A-43E, 44A-44G or 45A-45E.

Targeting domains, disclosed herein, may comprises the 24-mer described in Tables 43A-43E, 44A-44G or 45A-45E, e.g., the targeting domains of 25 or more nucleotides may comprise the 24-mer gRNAs described in Tables 43A-43E, 44A-44G or 45A-45E. gRNAs were identified for both single-gRNA nuclease cleavage and for a dual-gRNA paired "nickase" strategy. Criteria for selecting gRNAs and the determination for which gRNAs can be used for the dual-gRNA paired "nickase" strategy is based on two considerations:

1. gRNA pairs should be oriented on the DNA such that PAMs are facing out and

cutting with the D10A Cas9 nickase will result in 5' overhangs.

2. An assumption that cleaving with dual nickase pairs will result in deletion of the entire intervening sequence at a reasonable frequency. However, cleaving with dual nickase pairs can also result in indel mutations at the site of only one of the gRNAs. Candidate pair members can be tested for how efficiently they remove the entire sequence versus causing indel mutations at the site of one gRNA.

The targeting domains discussed herein can be incorporated into the gRNAs described herein. gRNAs were identified and ranked into 5 tiers for S. pyogenes (Tables 43A-43E), and N. meningitidis (Tables 45A-45E); and 7 tiers for S. aureus (Tables 44A-44G). For S. pyogenes, and N. meningitidis, the targeting domain for tier 1 gRNA molecules were selected based on (1) distance to a target site (e.g., start codon), e.g., within 500bp (e.g., downstream) of the target site (e.g., start codon), (2) a high level of orthogonality and (3) the presence of 5'G. The targeting domain for tier 2 gRNA molecules were selected based on (1) distance to a target site (e.g., start codon), e.g., within 500bp (e.g., downstream) of the target site (e.g., start codon) and (2) a high level of orthogonality. The targeting domain for tier 3 gRNA molecules were selected based on (1) distance to a target site (e.g., start codon), e.g., within 500bp (e.g., downstream) of the target site (e.g., start codon) and (2) the presence of 5'G. The targeting domain for tier 4 gRNA molecules were selected based on distance to a target site (e.g., start codon), e.g., within 500bp (e.g., downstream) of the target site (e.g., start codon). The targeting domain for tier 5 gRNA molecules were selected based on distance to the target site (e.g., start codon), e.g., within reminder of the coding sequence, e.g., downstream of the first 500bp of coding sequence (e.g.,

131

5535.1 anywhere from +500 (relative to the start codon) to the stop codon). For S. aureus, the targeting domain for tier 1 gRNA molecules were selected based on (1) distance to a target site (e.g., start codon), e.g., within 500bp (e.g., downstream) of the target site (e.g., start codon), (2) a high level of orthogonality, (3) the presence of 5'G and (4) PAM is NNGRRT. The targeting domain for tier 2 gRNA molecules were selected based on (1) distance to a target site (e.g., start codon), e.g., within 500bp (e.g., downstream) of the target site (e.g., start codon), (2) a high level of orthogonality, and (3) PAM is NNGRRT. The targeting domain for tier 3 gRNA molecules were selected based on (1) distance to a target site (e.g., start codon), e.g., within 500bp (e.g., downstream) of the target site (e.g., start codon) and (2) PAM is NNGRRT. The targeting domain for tier 4 gRNA molecules were selected based on (1) distance to a target site (e.g., start codon), e.g., within 500bp (e.g., downstream) of the target site (e.g., start codon) and (2) PAM is NNGRRV. The targeting domain for tier 5 gRNA molecules were selected based on (1) distance to the target site (e.g., start codon), e.g., within reminder of the coding sequence, e.g.,

downstream of the first 500bp of coding sequence (e.g., anywhere from +500 (relative to the start codon) to the stop codon), (2) the presence of 5'G and (3) PAM is NNGRRT. The targeting domain for tier 6 gRNA molecules were selected based on (1) distance to the target site (e.g., start codon), e.g., within reminder of the coding sequence, e.g., downstream of the first 500bp of coding sequence (e.g., anywhere from +500 (relative to the start codon) to the stop codon) and (2) PAM is NNGRRT. The targeting domain for tier 7 gRNA molecules were selected based on (1) distance to the target site (e.g., start codon), e.g., within reminder of the coding sequence, e.g., downstream of the first 500bp of coding sequence (e.g., anywhere from +500 (relative to the start codon) to the stop codon) and (2) PAM is NNGRRV. Note that tiers are non-inclusive (each gRNA is listed only once for the strategy). In certain instances, no gRNA was identified based on the criteria of the particular tier.

Strategies to identify gRNAs for S. pyogenes, S. Aureus, and N. meningitidis to knock down the SCNN1A gene

As an example, three strategies were utilized to identify gRNAs for use with S. pyogenes, S. aureus and N. meningitidis Cas9 enzymes.

Guide RNAs (gRNAs) for use with S. pyogenes, S. aureus and N. meningitidis Cas9s were identified using a DNA sequence searching algorithm. Guide RNA design was carried out

132

5535.1 using a custom guide RNA design software based on the public tool cas-offinder (reference:Cas- OFFinder: a fast and versatile algorithm that searches for potential off-target sites of Cas9 RNA- guided endonucleases., Bioinformatics. 2014 Feb 17. Bae S, Park J, Kim JS. PMID:24463181). Said custom guide RNA design software scores guides after calculating their genomewide off- target propensity. Typically matches ranging from perfect matches to 7 mismatches are considered for guides ranging in length from 17 to 24. Once the off-target sites are

computationally determined , an aggregate score is calculated for each guide and summarized in a tabular output using a web-interface. In addition to identifying potential gRNA sites adjacent to PAM sequences, the software also identifies all PAM adjacent sequences that differ by 1, 2, 3 or more nucleotides from the selected gRNA sites. Genomic DNA sequence for each gene was obtained from the UCSC Genome browser and sequences were screened for repeat elements using the publically available RepeatMasker program. RepeatMasker searches input DNA sequences for repeated elements and regions of low complexity. The output is a detailed annotation of the repeats present in a given query sequence.

Following identification, gRNAs were ranked into tiers based on their distance to the target site, their orthogonality and presence of a 5' G (based on identification of close matches in the human genome containing a relavant PAM (e.g., in the case of S. pyogenes, a NGG PAM, in the case of S. aureus, a NNGRRT or NNGRRV PAM, and in the case of N. meningitidis, a NNNNGATT or NNNNGCTT PAM). Orthogonality refers to the number of sequences in the human genome that contain a minimum number of mismatches to the target sequence. A "high level of orthogonality" or "good orthogonality" may, for example, refer to 20-mer gRNAs that have no identical sequences in the human genome besides the intended target, nor any sequences that contain one or two mismatches in the target sequence. Targeting domains with good orthogonality are selected to minimize off-target DNA cleavage.

As an example, for S. pyogenes and N. meningitidis targets, 17-mer, or 20-mer gRNAs were designed. As another example, for S. aureus targets, 18-mer, 19-mer, 20-mer, 21-mer, 22- mer, 23-mer and 24-mer gRNAs were designed. Targeting domains, disclosed herein, may comprise the 17-mer described in Tables 46A-46E, 47A-47G or 48A-48E, e.g., the targeting domains of 18 or more nucleotides may comprise the 17-mer gRNAs described in Tables 46A- 46E, 47A-47G or 48A-48E. Targeting domains, disclosed herein, may comprises the 18-mer described in Tables 46A-46E, 47A-47G or 48A-48E, e.g., the targeting domains of 19 or more

133

5535.1 nucleotides may comprise the 18-mer gRNAs described in Tables 46A-46E, 47A-47G or 48A- 48E. Targeting domains, disclosed herein, may comprises the 19-mer described in Tables 46A- 46E, 47A-47G or 48A-48E, e.g., the targeting domains of 20 or more nucleotides may comprise the 19-mer gRNAs described in Tables 46A-46E, 47A-47G or 48A-48E. Targeting domains, disclosed herein, may comprises the 20-mer gRNAs described in Tables 46A-46E, 47A-47G or 48A-48E, e.g., the targeting domains of 21 or more nucleotides may comprise the 20-mer gRNAs described in Tables 46A-46E, 47A-47G or 48A-48E. Targeting domains, disclosed herein, may comprises the 21-mer described in Tables 46A-46E, 47A-47G or 48A-48E, e.g., the targeting domains of 22 or more nucleotides may comprise the 21-mer gRNAs described in

Tables 46A-46E, 47A-47G or 48A-48E. Targeting domains, disclosed herein, may comprises the 22-mer described in Tables 46A-46E, 47A-47G or 48A-48E, e.g., the targeting domains of 23 or more nucleotides may comprise the 22-mer gRNAs described in Tables 46A-46E, 47A- 47G or 48A-48E. Targeting domains, disclosed herein, may comprises the 23-mer described in Tables 46A-46E, 47A-47G or 48A-48E,e.g., the targeting domains of 24 or more nucleotides may comprise the 23-mer gRNAs described in Tables 46A-46E, 47A-47G or 48A-48E.

Targeting domains, disclosed herein, may comprises the 24-mer described in Tables 46A-46E, 47A-47G or 48A-48E, e.g., the targeting domains of 25 or more nucleotides may comprise the 24-mer gRNAs described in Tables 46A-46E, 47A-47G or 48A-48E.

The targeting domains discussed herein can be incorporated into the gRNAs described herein. gRNAs were identified and ranked into 5 tiers for S. pyogenes (Tables 46A-46E), and N. meningitidis (Tables 48A-48E); and 7 tiers for S. aureus (Tables 47A-47G). For S. pyogenes, and N. meningitidis, the targeting domain for tier 1 gRNA molecules were selected based on (1) distance to a target site, e.g., within 500 bp (e.g., upstream or downstream) of a transcription start site (TSS), (2) a high level of orthogonality and (3) the presence of 5'G. The targeting domain for tier 2 gRNA molecules were selected based on (1) distance to a target site, e.g., within 500 bp (e.g., upstream or downstream) of a transcription start site (TSS) and (2) a high level of orthogonality. The targeting domain for tier 3 gRNA molecules were selected based on (1) distance to a target site, e.g., within 500 bp (e.g., upstream or downstream) of a transcription start site (TSS) and (2) the presence of 5'G. The targeting domain for tier 4 gRNA molecules were selected based on distance to a target site, e.g., within 500 bp (e.g., upstream or downstream) of a transcription start site (TSS). The targeting domain for tier 5 gRNA molecules were selected

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5535.1 based on distance to the target site, e.g., within the additional 500 bp (e.g., upstream or downstream) of a transcription start site (TSS), e.g., extending to lkb upstream and downstream of a TSS. For S. aureus, the targeting domain for tier 1 gRNA molecules were selected based on (1) distance to a target site, e.g., within 500 bp (e.g., upstream or downstream) of a transcription start site (TSS), (2) a high level of orthogonality, (3) the presence of 5'G and (4) PAM is

NNGRRT. The targeting domain for tier 2 gRNA molecules were selected based on (1) distance to a target site, e.g., within 500 bp (e.g., upstream or downstream) of a transcription start site (TSS), (2) a high level of orthogonality, and (3) PAM is NNGRRT. The targeting domain for tier 3 gRNA molecules were selected based on (1) distance to a target site, e.g., within 500 bp (e.g., upstream or downstream) of a transcription start site (TSS) and (2) PAM is NNGRRT. The targeting domain for tier 4 gRNA molecules were selected based on (1) distance to a target site, e.g., within 500 bp (e.g., upstream or downstream) of a transcription start site (TSS) and (2) PAM is NNGRRV. The targeting domain for tier 5 gRNA molecules were selected based on (1) distance to the target site, e.g., within the additional 500 bp (e.g., upstream or downstream) of a transcription start site (TSS), e.g., extending to lkb upstream and downstream of a TSS , (2) the presence of 5'G and (3) PAM is NNGRRT. The targeting domain for tier 6 gRNA molecules were selected based on (1) distance to the target site, e.g., within the additional 500 bp (e.g., upstream or downstream) of a transcription start site (TSS), e.g., extending to lkb upstream and downstream of a TSS and (2) PAM is NNGRRT. The targeting domain for tier 7 gRNA molecules were selected based on (1) distance to the target site, e.g., within the additional 500 bp (e.g., upstream or downstream) of a transcription start site (TSS), e.g., extending to lkb upstream and downstream of a TSS and (2) PAM is NNGRRV. Note that tiers are non-inclusive (each gRNA is listed only once for the strategy). In certain instances, no gRNA was identified based on the criteria of the particular tier.

Strategies to identify gRNAs for S. pyogenes, S. Aureus, and N. for correcting a mutation (e.g., delF508, G551D, G542X, N1303K, R117H, W1282X, R553X, 2789+5G->A, or 3272-26A->G) in the CFTR gene

As an example, three strategies were utilized to identify gRNAs for use with S. pyogenes, S. aureus and N. meningitidis Cas9 enzymes.

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5535.1 In the first strategy, guide RNAs (gRNAs) for use with the S. pyogenes Cas9 (Tables 1A- 1C or 2A-2C) were identified using the publically available web-based ZiFiT server (Fu et al., Improving CRISPR-Cas nuclease specificity using truncated guide RNAs. Nat Biotechnol. 2014 Jan 26. doi: 10.1038/nbt.2808. PubMed PMID: 24463574, for the original references see Sander et al., 2007, NAR 35:W599-605; Sander et al., 2010, NAR 38: W462-8). In addition to identifying potential gRNA sites adjacent to PAM sequences, the software also identifies all PAM adjacent sequences that differ by 1, 2, 3 or more nucleotides from the selected gRNA sites. Genomic DNA sequence for each gene was obtained from the UCSC Genome browser and sequences were screened for repeat elements using the publically available Repeat-Masker program. RepeatMmasker searches input DNA sequences for repeated elements and regions of low complexity. The output is a detailed annotation of the repeats present in a given query sequence. Following identification, gRNAs for use with a S. pyogenes Cas9 were ranked into 3 or 4 tiers, as described below.

The gRNAs in tier 1 were selected based on their distance to the target site and their orthogonality in the genome (based on the ZiFiT identification of close matches in the human genome containing an NGG PAM). As an example, for all targets, both 17-mer and 20-mer gRNAs were designed. gRNAs were also selected both for single-gRNA nuclease cutting and for the dual gRNA nickase strategy. Criteria for selecting gRNAs and the determination for which gRNAs can be used for which strategy is based on several considerations:

3. For the dual nickase strategy, gRNA pairs should be oriented on the DNA such that

PAMs are facing out and cutting with the D10A Cas9 nickase will result in 5' overhangs.

4. An assumption that cleaving with dual nickase pairs will result in deletion of the

entire intervening sequence at a reasonable frequency. However, it will also often result in indel mutations at the site of only one of the gRNAs. Candidate pair members can be tested for how efficiently they remove the entire sequence versus just causing indel mutations at the site of one gRNA.

While it can be desirable to have gRNAs start with a 5' G, this requirement was relaxed for some gRNAs in tier 1 in order to identify guides in the correct orientation, within a reasonable distance to the mutation and with a high level of orthogonality. In order to find a pair for the dual-nickase strategy it was necessary to either extend the distance from the mutation or

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5535.1 remove the requirement for the 5'G. For selection of tier 2 gRNAs, the distance restriction was relaxed in some cases such that a longer sequence was scanned, but the 5'G was required for all gRNAs. Whether or not the distance requirement was relaxed depended on how many sites were found within the original search window. Tier 3 uses the same distance restriction as tier 2, but removes the requirement for a 5'G. Note that tiers are non-inclusive (each gRNA is listed only once).

As discussed above, gRNAs were identified for single-gRNA nuclease cleavage as well as for a dual-gRNA paired "nickase" strategy, as indicated.

gRNAs for use with the N. meningitidis (Tables IE or 2E) and S. aureus (Tables ID or 2D) Cas9s were identified manually by scanning genomic DNA sequence for the presence of PAM sequences. These gRNAs were not separated into tiers, but are provided in single lists for each species.

In a second strategy, Guide RNAs (gRNAs) for use with S. pyogenes, S. aureus and N. meningitidis Cas9s were identified using a DNA sequence searching algorithm. Guide RNA design was carried out using a custom guide RNA design software based on the public tool cas- offinder (reference:Cas-OFFinder: a fast and versatile algorithm that searches for potential off- target sites of Cas9 RNA-guided endonucleases., Bioinformatics. 2014 Feb 17. Bae S, Park J, Kim JS. PMID:24463181). Said custom guide RNA design software scores guides after calculating their genomewide off-target propensity. Typically matches ranging from perfect matches to 7 mismatches are considered for guides ranging in length from 17 to 24. Once the off- target sites are computationally determined , an aggregate score is calculated for each guide and summarized in a tabular output using a web-interface. In addition to identifying potential gRNA sites adjacent to PAM sequences, the software also identifies all PAM adjacent sequences that differ by 1, 2, 3 or more nucleotides from the selected gRNA sites. Genomic DNA sequence for each gene was obtained from the UCSC Genome browser and sequences were screened for repeat elements using the publically available RepeatMasker program. RepeatMasker searches input DNA sequences for repeated elements and regions of low complexity. The output is a detailed annotation of the repeats present in a given query sequence.

Following identification, gRNAs were ranked into tiers based on their distance to the target site, their orthogonality and presence of a 5' G (based on identification of close matches in

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5535.1 the human genome containing a relavant PAM (e.g., in the case of S. pyogenes, a NGG PAM, in the case of S. aureus, a NNGRRT or NNGRRV PAM, and in the case of N. meningitidis, a NNNNGATT or NNNNGCTT PAM). Orthogonality refers to the number of sequences in the human genome that contain a minimum number of mismatches to the target sequence. A "high level of orthogonality" or "good orthogonality" may, for example, refer to 20-mer gRNAs that have no identical sequences in the human genome besides the intended target, nor any sequences that contain one or two mismatches in the target sequence. Targeting domains with good orthogonality are selected to minimize off-target DNA cleavage.

As an example, for S. pyogenes and N. meningitidis targets, 17-mer, or 20-mer gRNAs were designed. As another example, for S. aureus targets, 18-mer, 19-mer, 20-mer, 21-mer, 22- mer, 23-mer and 24-mer gRNAs were designed. Targeting domains, disclosed herein, may comprise the 17-mer described in Tables 4A-4D, 5A-5E, 6A-6C, 7A-7D, 8A-8E, 9A-9B, 10A- 10C, 11A-11E, 12A-12C, 13A-13D, 14A-14E, 15A-15C, or 16A-16D, 17A-17E, 18A-18C, 19A-19D, 20A-20E, 21A-21B, 22A-22D, 23A-23E, 24A-24D, 25A-25D, 26A-26E, 27A-27D, 28A-28D, 29A-29E, or 30A-30B, e.g., the targeting domains of 18 or more nucleotides may comprise the 17-mer gRNAs described in Tables 4A-4D, 5A-5E, 6A-6C, 7A-7D, 8A-8E, 9A- 9B, lOA-lOC, 11A-11E, 12A-12C, 13A-13D, 14A-14E, 15A-15C, or 16A-16D, 17A-17E, 18A- 18C, 19A-19D, 20A-20E, 21A-21B, 22A-22D, 23A-23E, 24A-24D, 25A-25D, 26A-26E, 27A- 27D, 28A-28D, 29A-29E, or 30A-30B. Targeting domains, disclosed herein, may comprises the 18-mer described in Tables 4A-4D, 5A-5E, 6A-6C, 7A-7D, 8A-8E, 9A-9B, lOA-lOC, 11A- 11E, 12A-12C, 13A-13D, 14A-14E, 15A-15C, or 16A-16D, 17A-17E, 18A-18C, 19A-19D, 20A-20E, 21A-21B, 22A-22D, 23A-23E, 24A-24D, 25A-25D, 26A-26E, 27A-27D, 28A-28D, 29A-29E, or 30A-30B, e.g., the targeting domains of 19 or more nucleotides may comprise the 18-mer gRNAs described in Tables 4A-4D, 5A-5E, 6A-6C, 7A-7D, 8A-8E, 9A-9B, lOA-lOC, 11A-11E, 12A-12C, 13A-13D, 14A-14E, 15A-15C, or 16A-16D, 17A-17E, 18A-18C, 19A- 19D, 20A-20E, 21A-21B, 22A-22D, 23A-23E, 24A-24D, 25A-25D, 26A-26E, 27A-27D, 28A- 28D, 29A-29E, or 30A-30B. Targeting domains, disclosed herein, may comprises the 19-mer described in Tables 4A-4D, 5A-5E, 6A-6C, 7A-7D, 8A-8E, 9A-9B, lOA-lOC, 11A-11E, 12A- 12C, 13A-13D, 14A-14E, 15A-15C, or 16A-16D, 17A-17E, 18A-18C, 19A-19D, 20A-20E, 21A-21B, 22A-22D, 23A-23E, 24A-24D, 25A-25D, 26A-26E, 27A-27D, 28A-28D, 29A-29E, or 30A-30B, e.g., the targeting domains of 20 or more nucleotides may comprise the 19-mer

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5535.1 gRNAs described in Tables 4A-4D, 5A-5E, 6A-6C, 7A-7D, 8A-8E, 9A-9B, lOA-lOC, 11A- 11E, 12A-12C, 13A-13D, 14A-14E, 15A-15C, or 16A-16D, 17A-17E, 18A-18C, 19A-19D, 20A-20E, 21A-21B, 22A-22D, 23A-23E, 24A-24D, 25A-25D, 26A-26E, 27A-27D, 28A-28D, 29A-29E, or 30A-30B. Targeting domains, disclosed herein, may comprises the 20-mer gRNAs described in Tables 4A-4D, 5A-5E, 6A-6C, 7A-7D, 8A-8E, 9A-9B, lOA-lOC, 11A-11E, 12A- 12C, 13A-13D, 14A-14E, 15A-15C, or 16A-16D, 17A-17E, 18A-18C, 19A-19D, 20A-20E, 21A-21B, 22A-22D, 23A-23E, 24A-24D, 25A-25D, 26A-26E, 27A-27D, 28A-28D, 29A-29E, or 30A-30B, e.g., the targeting domains of 21 or more nucleotides may comprise the 20-mer gRNAs described in Tables 4A-4D, 5A-5E, 6A-6C, 7A-7D, 8A-8E, 9A-9B, lOA-lOC, 11A- HE, 12A-12C, 13A-13D, 14A-14E, 15A-15C, or 16A-16D, 17A-17E, 18A-18C, 19A-19D, 20A-20E, 21A-21B, 22A-22D, 23A-23E, 24A-24D, 25A-25D, 26A-26E, 27A-27D, 28A-28D, 29A-29E, or 30A-30B. Targeting domains, disclosed herein, may comprises the 21-mer described in Tables 4A-4D, 5A-5E, 6A-6C, 7A-7D, 8A-8E, 9A-9B, lOA-lOC, 11A-11E, 12A- 12C, 13A-13D, 14A-14E, 15A-15C, or 16A-16D, 17A-17E, 18A-18C, 19A-19D, 20A-20E, 21A-21B, 22A-22D, 23A-23E, 24A-24D, 25A-25D, 26A-26E, 27A-27D, 28A-28D, 29A-29E, or 30A-30B, e.g., the targeting domains of 22 or more nucleotides may comprise the 21-mer gRNAs described in Tables 4A-4D, 5A-5E, 6A-6C, 7A-7D, 8A-8E, 9A-9B, lOA-lOC, 11A- 11E, 12A-12C, 13A-13D, 14A-14E, 15A-15C, or 16A-16D, 17A-17E, 18A-18C, 19A-19D, 20A-20E, 21A-21B, 22A-22D, 23A-23E, 24A-24D, 25A-25D, 26A-26E, 27A-27D, 28A-28D, 29A-29E, or 30A-30B. Targeting domains, disclosed herein, may comprises the 22-mer described in Tables 4A-4D, 5A-5E, 6A-6C, 7A-7D, 8A-8E, 9A-9B, lOA-lOC, 11A-11E, 12A- 12C, 13A-13D, 14A-14E, 15A-15C, or 16A-16D, 17A-17E, 18A-18C, 19A-19D, 20A-20E, 21A-21B, 22A-22D, 23A-23E, 24A-24D, 25A-25D, 26A-26E, 27A-27D, 28A-28D, 29A-29E, or 30A-30B, e.g., the targeting domains of 23 or more nucleotides may comprise the 22-mer gRNAs described in Tables 4A-4D, 5A-5E, 6A-6C, 7A-7D, 8A-8E, 9A-9B, lOA-lOC, 11A- 11E, 12A-12C, 13A-13D, 14A-14E, 15A-15C, or 16A-16D, 17A-17E, 18A-18C, 19A-19D, 20A-20E, 21A-21B, 22A-22D, 23A-23E, 24A-24D, 25A-25D, 26A-26E, 27A-27D, 28A-28D, 29A-29E, or 30A-30B. Targeting domains, disclosed herein, may comprises the 23-mer described in Tables 4A-4D, 5A-5E, 6A-6C, 7A-7D, 8A-8E, 9A-9B, lOA-lOC, 11A-11E, 12A- 12C, 13A-13D, 14A-14E, 15A-15C, or 16A-16D, 17A-17E, 18A-18C, 19A-19D, 20A-20E, 21A-21B, 22A-22D, 23A-23E, 24A-24D, 25A-25D, 26A-26E, 27A-27D, 28A-28D, 29A-29E,

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5535.1 or 30A-30B,e.g., the targeting domains of 24 or more nucleotides may comprise the 23-mer gRNAs described in Tables 4A-4D, 5A-5E, 6A-6C, 7A-7D, 8A-8E, 9A-9B, lOA-lOC, 11A- 11E, 12A-12C, 13A-13D, 14A-14E, 15A-15C, or 16A-16D, 17A-17E, 18A-18C, 19A-19D, 20A-20E, 21A-21B, 22A-22D, 23A-23E, 24A-24D, 25A-25D, 26A-26E, 27A-27D, 28A-28D, 29A-29E, or 30A-30B. Targeting domains, disclosed herein, may comprises the 24-mer described in Tables 4A-4D, 5A-5E, 6A-6C, 7A-7D, 8A-8E, 9A-9B, lOA-lOC, 11A-11E, 12A- 12C, 13A-13D, 14A-14E, 15A-15C, or 16A-16D, 17A-17E, 18A-18C, 19A-19D, 20A-20E, 21A-21B, 22A-22D, 23A-23E, 24A-24D, 25A-25D, 26A-26E, 27A-27D, 28A-28D, 29A-29E, or 30A-30B, e.g., the targeting domains of 25 or more nucleotides may comprise the 24-mer gRNAs described in Tables 4A-4D, 5A-5E, 6A-6C, 7A-7D, 8A-8E, 9A-9B, lOA-lOC, 11A- 11E, 12A-12C, 13A-13D, 14A-14E, 15A-15C, or 16A-16D, 17A-17E, 18A-18C, 19A-19D, 20A-20E, 21A-21B, 22A-22D, 23A-23E, 24A-24D, 25A-25D, 26A-26E, 27A-27D, 28A-28D, 29A-29E, or 30A-30B. gRNAs were identified for both single-gRNA nuclease cleavage and for a dual-gRNA paired "nickase" strategy. Criteria for selecting gRNAs and the determination for which gRNAs can be used for the dual-gRNA paired "nickase" strategy is based on two considerations:

1. gRNA pairs should be oriented on the DNA such that PAMs are facing out and

cutting with the D10A Cas9 nickase will result in 5' overhangs.

2. An assumption that cleaving with dual nickase pairs will result in deletion of the entire intervening sequence at a reasonable frequency. However, cleaving with dual nickase pairs can also result in indel mutations at the site of only one of the gRNAs. Candidate pair members can be tested for how efficiently they remove the entire sequence versus causing indel mutations at the site of one gRNA.

The targeting domains discussed herein can be incorporated into the gRNAs described herein.

In an embodiment, gRNAs were identified and ranked into 4 tiers for S. pyogenes

(Tables 4A-4D, 7A-7D, lOA-lOC, 13A-13D, 16A-16D, 19A-19D, 12A-12D, 22A-22D, 25A- 25D or 28A-28D), and N. meningitidis (Tables 6A-6C, 9A-9B, 12A-12C, 15A-15C, 18A-18C, 21A-21B, 24A-24D, 27A-27D, or 30A-30B); and 5 tiers for S. aureus (Tables 5A-5E, 8A-8E, 11A-11E, 14A-14E, 17A-17E, 20A-20E, 23A-23E, 26A-26E, or 29A-29E). For S. pyogenes, and N. meningitidis, the targeting domaior tier 1 gRNA molecules were selected based on (1) distance to a target site, e.g., within 200 bp from a mutation (e.g., delF508, G551D, G542X,

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5535.1 N1303K, R117H, W1282X, R553X, 2789+5G->A, or 3272-26A->G) , (2) a high level of orthogonality and (3) the presence of 5'G. The targeting domain for tier 2 gRNA molecules were selected based on (1) distance to a target site, e.g., within 200 bp from a mutation (e.g., delF508, G551D, G542X, N1303K, R117H, W1282X, R553X, 2789+5G->A, or 3272-26A->G) and (2) a high level of orthogonality. The targeting domain for tier 3 gRNA molecules were selected based on (1) distance to a target site, e.g., within 200 bp from a mutation (e.g., delF508, G551D, G542X, N1303K, R117H, W1282X, R553X, 2789+5G->A, or 3272-26A->G) and (2) the presence of 5'G. The targeting domain for tier 4 gRNA molecules were selected based on distance to a target site, e.g., within 200 bp from a mutation (e.g., delF508, G551D, G542X, N1303K, Rl 17H, W1282X, R553X, 2789+5G->A, or 3272-26A->G) . For S. aureus, the targeting domain for tier 1 gRNA molecules were selected based on (1) distance to a target site, e.g., within 200 bp from a mutation (e.g., delF508, G551D, G542X, N1303K, R117H, W1282X, R553X, 2789+5G->A, or 3272-26A->G) , (2) a high level of orthogonality, (3) the presence of 5'G and (4) PAM is NNGRRT. The targeting domain for tier 2 gRNA molecules were selected based on (1) distance to a target site, e.g., within 200 bp from a mutation (e.g., delF508, G551D, G542X, N1303K, R117H, W1282X, R553X, 2789+5G->A, or 3272-26A->G) , (2) a high level of orthogonality, and (3) PAM is NNGRRT. The targeting domain for tier 3 gRNA molecules were selected based on (1) distance to a target site, e.g., within 200 bp from a mutation (e.g., delF508, G551D, G542X, N1303K, R117H, W1282X, R553X, 2789+5G->A, or 3272-26A->G) , (2) the presence of a 5'G and (2) PAM is NNGRRT. The targeting domain for tier 4 gRNA molecules were selected based on (1) distance to a target site, e.g., within 200 bp from a mutation (e.g., delF508, G551D, G542X, N1303K, R117H, W1282X, R553X, 2789+5G->A, or 3272-26A->G) and (2) PAM is NNGRRT. The targeting domain for tier 5 gRNA molecules were selected based on (1) (1) distance to a target site, e.g., within 200 bp from a mutation (e.g., delF508, G551D, G542X, N1303K, R117H, W1282X, R553X, 2789+5G->A, or 3272-26A->G) and (2) PAM is NNGRRV. Note that tiers are non-inclusive (each gRNA is listed only once for the strategy). In certain instances, no gRNA was identified based on the criteria of the particular tier.

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5535.1 Strategies to identify gRNAs for S. pyogenes, S. Aureus, and N. meningitidis for targeting an intronic mutation (e.g., 3849+10kbC->T or 3272-26A->G) regions of the CFTR gene (e.g., mediated by NHEJ)

As an example, three strategies were utilized to identify gRNAs for use with S. pyogenes, S. aureus and N. meningitidis Cas9 enzymes.

Guide RNAs (gRNAs) for use with S. pyogenes, S. aureus and N. meningitidis Cas9s were identified using a DNA sequence searching algorithm. Guide RNA design was carried out using a custom guide RNA design software based on the public tool cas-offinder (reference:Cas- OFFinder: a fast and versatile algorithm that searches for potential off-target sites of Cas9 RNA- guided endonucleases., Bioinformatics. 2014 Feb 17. Bae S, Park J, Kim JS. PMID:24463181). Said custom guide RNA design software scores guides after calculating their genomewide off- target propensity. Typically matches ranging from perfect matches to 7 mismatches are considered for guides ranging in length from 17 to 24. Once the off-target sites are

computationally determined, an aggregate score is calculated for each guide and summarized in a tabular output using a web-interface. In addition to identifying potential gRNA sites adjacent to PAM sequences, the software also identifies all PAM adjacent sequences that differ by 1, 2, 3 or more nucleotides from the selected gRNA sites. Genomic DNA sequence for each gene was obtained from the UCSC Genome browser and sequences were screened for repeat elements using the publically available RepeatMasker program. RepeatMasker searches input DNA sequences for repeated elements and regions of low complexity. The output is a detailed annotation of the repeats present in a given query sequence.

Following identification, gRNAs were ranked into tiers based on their distance to the target site, their orthogonality and presence of a 5' G (based on identification of close matches in the human genome containing a relavant PAM (e.g., in the case of S. pyogenes, a NGG PAM, in the case of S. aureus, a NNGRRT or NNGRRV PAM, and in the case of N. meningitidis, a

NNNNGATT or NNNNGCTT PAM). Orthogonality refers to the number of sequences in the human genome that contain a minimum number of mismatches to the target sequence. A "high level of orthogonality" or "good orthogonality" may, for example, refer to 20-mer gRNAs that have no identical sequences in the human genome besides the intended target, nor any sequences that contain one or two mismatches in the target sequence. Targeting domains with good orthogonality are selected to minimize off-target DNA cleavage.

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5535.1 As an example, for S. pyogenes and N. meningitidis targets, 17-mer, or 20-mer gRNAs were designed. As another example, for S. aureus targets, 18-mer, 19-mer, 20-mer, 21-mer, 22- mer, 23-mer and 24-mer gRNAs were designed. Targeting domains, disclosed herein, may comprise the 17-mer described in Tables 31A-31D, 32A-32D, 33A-33B, 34A-34D, 35A-35D, 36A-36D, e.g., the targeting domains of 18 or more nucleotides may comprise the 17-mer gRNAs described in Tables 31A-31D, 32A-32D, 33A-33B, 34A-34D, 35A-35D, 36A-36D. Targeting domains, disclosed herein, may comprises the 18-mer described in Tables 31A-31D, 32A-32D, 33A-33B, 34A-34D, 35A-35D, 36A-36D, e.g., the targeting domains of 19 or more nucleotides may comprise the 18-mer gRNAs described in Tables 31A-31D, 32A-32D, 33A- 33B, 34A-34D, 35A-35D, 36A-36D. Targeting domains, disclosed herein, may comprises the 19-mer described in Tables 31A-31D, 32A-32D, 33A-33B, 34A-34D, 35A-35D, 36A-36D, e.g., the targeting domains of 20 or more nucleotides may comprise the 19-mer gRNAs described in Tables 31A-31D, 32A-32D, 33A-33B, 34A-34D, 35A-35D, 36A-36D. Targeting domains, disclosed herein, may comprises the 20-mer gRNAs described in Tables 31A-31D, 32A-32D, 33A-33B, 34A-34D, 35A-35D, 36A-36D, e.g., the targeting domains of 21 or more nucleotides may comprise the 20-mer gRNAs described in Tables 31A-31D, 32A-32D, 33A-33B, 34A-34D, 35A-35D, 36A-36D. Targeting domains, disclosed herein, may comprises the 21-mer described in Tables 31A-31D, 32A-32D, 33A-33B, 34A-34D, 35A-35D, 36A-36D, e.g., the targeting domains of 22 or more nucleotides may comprise the 21-mer gRNAs described in Tables 31 A- 31D, 32A-32D, 33A-33B, 34A-34D, 35A-35D, 36A-36D. Targeting domains, disclosed herein, may comprises the 22-mer described in Tables 31A-31D, 32A-32D, 33A-33B, 34A-34D, 35A- 35D, 36A-36D, e.g., the targeting domains of 23 or more nucleotides may comprise the 22-mer gRNAs described in Tables 31A-31D, 32A-32D, 33A-33B, 34A-34D, 35A-35D, 36A-36D. Targeting domains, disclosed herein, may comprises the 23-mer described in Tables 31A-31D, 32A-32D, 33A-33B, 34A-34D, 35A-35D, 36A-36D,e.g., the targeting domains of 24 or more nucleotides may comprise the 23-mer gRNAs described in Tables 31A-31D, 32A-32D, 33A- 33B, 34A-34D, 35A-35D, 36A-36D. Targeting domains, disclosed herein, may comprises the 24-mer described in Tables 31A-31D, 32A-32D, 33A-33B, 34A-34D, 35A-35D, 36A-36D, e.g., the targeting domains of 25 or more nucleotides may comprise the 24-mer gRNAs described in Tables 31A-31D, 32A-32D, 33A-33B, 34A-34D, 35A-35D, 36A-36D. gRNAs were identified for both single-gRNA nuclease cleavage and for a dual-gRNA paired "nickase" strategy. Criteria

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5535.1 for selecting gRNAs and the determination for which gRNAs can be used for the dual-gRNA paired "nickase" strategy is based on two considerations:

1. gRNA pairs should be oriented on the DNA such that PAMs are facing out and

cutting with the D10A Cas9 nickase will result in 5' overhangs.

2. An assumption that cleaving with dual nickase pairs will result in deletion of the entire intervening sequence at a reasonable frequency. However, cleaving with dual nickase pairs can also result in indel mutations at the site of only one of the gRNAs. Candidate pair members can be tested for how efficiently they remove the entire sequence versus causing indel mutations at the site of one gRNA.

The targeting domains discussed herein can be incorporated into the gRNAs described herein.

In an embodiment, gRNAs were identified and ranked into 4 tiers for S. pyogenes

(Tables 31A-31D or 34A-34D), and N. meningitidis (Tables 33A-33B or 36A-36D); and 4 tiers for S. aureus (Tables 32A-32D or 35A-35D). For S. pyogenes, and N. meningitidis, the targeting domain for tier 1 gRNA molecules were selected based on (1) distance to a target site, e.g., within 500bp, e.g., within 200 bp from a mutation (e.g., 3849+10kbC->T or 3272-26A- >G), (2) a high level of orthogonality and (3) the presence of 5'G. The targeting domain for tier 2 gRNA molecules were selected based on (1) distance to a target site, e.g., within 500bp, e.g., within 200 bp from a mutation (e.g., 3849+10kbC->T or 3272-26A->G) and (2) a high level of orthogonality. The targeting domain for tier 3 gRNA molecules were selected based on (1) distance to a target site, e.g., within 500bp, e.g., within 200 bp from a mutation (e.g.,

3849+10kbC->T or 3272-26A->G) and (2) the presence of 5'G. The targeting domain for tier 4 gRNA molecules were selected based on distance to a target site, e.g., within 500bp, e.g., within 200 bp from a mutation (e.g., 3849+10kbC->T or 3272-26A->G). For S. aureus, the targeting domain for tier 1 gRNA molecules were selected based on (1) distance to a target site, e.g., within 500bp, e.g., within 200 bp from a mutation (e.g., 3849+10kbC->T or 3272-26A->G), (2) a high level of orthogonality, (3) the presence of 5'G and (4) PAM is NNGRRT. The targeting domain for tier 2 gRNA molecules were selected based on (1) distance to a target site, e.g., within 500bp, e.g., within 200 bp from a mutation (e.g., 3849+10kbC->T or 3272-26A->G), (2) a high level of orthogonality, and (3) PAM is NNGRRT. The targeting domain for tier 3 gRNA molecules were selected based on (1) distance to a target site, e.g., within 500bp, e.g., within 200 bp from a mutation (e.g., 3849+10kbC->T or 3272-26A->G) and (2) PAM is NNGRRT. The

144

5535.1 targeting domain for tier 4 gRNA molecules were selected based on (1) (1) distance to a target site, e.g., within 500bp, e.g., within 200 bp from a mutation (e.g., 3849+10kbC->T or 3272- 26A->G) and (2) PAM is NNGRRV. Note that tiers are non-inclusive (each gRNA is listed only once for the strategy). In certain instances, no gRNA was identified based on the criteria of the particular tier.

Strategies to identify gRNAs for S. pyogenes, S. Aureus, and N. for targeting an intronic region (e.g., intron 2 or intron 10) of the CFTR gene (e.g., mediated by cDNA)

Guide RNAs (gRNAs) for use with S. pyogenes, S. aureus and N. meningitidis Cas9s were identified using a DNA sequence searching algorithm. Guide RNA design was carried out using a custom guide RNA design software based on the public tool cas-offinder (reference:Cas- OFFinder: a fast and versatile algorithm that searches for potential off-target sites of Cas9 RNA- guided endonucleases., Bioinformatics. 2014 Feb 17. Bae S, Park J, Kim JS. PMID:24463181). Said custom guide RNA design software scores guides after calculating their genomewide off- target propensity. Typically matches ranging from perfect matches to 7 mismatches are considered for guides ranging in length from 17 to 24. Once the off-target sites are

computationally determined , an aggregate score is calculated for each guide and summarized in a tabular output using a web-interface. In addition to identifying potential gRNA sites adjacent to PAM sequences, the software also identifies all PAM adjacent sequences that differ by 1, 2, 3 or more nucleotides from the selected gRNA sites. Genomic DNA sequence for each gene was obtained from the UCSC Genome browser and sequences were screened for repeat elements using the publically available RepeatMasker program. RepeatMasker searches input DNA sequences for repeated elements and regions of low complexity. The output is a detailed annotation of the repeats present in a given query sequence.

Following identification, gRNAs were ranked into tiers based on their distance to the target site, their orthogonality and presence of a 5' G (based on identification of close matches in the human genome containing a relavant PAM (e.g., in the case of S. pyogenes, a NGG PAM, in the case of S. aureus, a NNGRRT or NNGRRV PAM, and in the case of N. meningitidis, a NNNNGATT or NNNNGCTT PAM). Orthogonality refers to the number of sequences in the human genome that contain a minimum number of mismatches to the target sequence. A "high level of orthogonality" or "good orthogonality" may, for example, refer to 20-mer gRNAs that

145

5535.1 have no identical sequences in the human genome besides the intended target, nor any sequences that contain one or two mismatches in the target sequence. Targeting domains with good orthogonality are selected to minimize off-target DNA cleavage.

As an example, for S. pyogenes and N. meningitidis targets, 17-mer, or 20-mer gRNAs were designed. As another example, for S. aureus targets, 18-mer, 19-mer, 20-mer, 21-mer, 22- mer, 23-mer and 24-mer gRNAs were designed. Targeting domains, disclosed herein, may comprise the 17-mer described in Tables 37A-37D, 38A-38E, 39A-39D, 40A-40D, 41A-41E, or 42A-42D, e.g., the targeting domains of 18 or more nucleotides may comprise the 17-mer gRNAs described in Tables 37A-37D, 38A-38E, 39A-39D, 40A-40D, 41A-41E, or 42A-42D. Targeting domains, disclosed herein, may comprises the 18-mer described in Tables 37A-37D, 38A-38E, 39A-39D, 40A-40D, 41A-41E, or 42A-42D, e.g., the targeting domains of 19 or more nucleotides may comprise the 18-mer gRNAs described in Tables 37A-37D, 38A-38E, 39A- 39D, 40A-40D, 41A-41E, or 42A-42D. Targeting domains, disclosed herein, may comprises the 19-mer described in Tables 37A-37D, 38A-38E, 39A-39D, 40A-40D, 41A-41E, or 42A-42D, e.g., the targeting domains of 20 or more nucleotides may comprise the 19-mer gRNAs described in Tables 37A-37D, 38A-38E, 39A-39D, 40A-40D, 41A-41E, or 42A-42D. Targeting domains, disclosed herein, may comprises the 20-mer gRNAs described in Tables 37A-37D, 38A-38E, 39A-39D, 40A-40D, 41A-41E, or 42A-42D, e.g., the targeting domains of 21 or more nucleotides may comprise the 20-mer gRNAs described in Tables 37A-37D, 38A-38E, 39A- 39D, 40A-40D, 41A-41E, or 42A-42D. Targeting domains, disclosed herein, may comprises the 21-mer described in Tables 37A-37D, 38A-38E, 39A-39D, 40A-40D, 41A-41E, or 42A-42D, e.g., the targeting domains of 22 or more nucleotides may comprise the 21-mer gRNAs described in Tables 37A-37D, 38A-38E, 39A-39D, 40A-40D, 41A-41E, or 42A-42D. Targeting domains, disclosed herein, may comprises the 22-mer described in Tables 37A-37D, 38A-38E, 39A-39D, 40A-40D, 41A-41E, or 42A-42D, e.g., the targeting domains of 23 or more nucleotides may comprise the 22-mer gRNAs described in Tables 37A-37D, 38A-38E, 39A-39D, 40A-40D, 41A-41E, or 42A-42D. Targeting domains, disclosed herein, may comprises the 23-mer described in Tables 37A-37D, 38A-38E, 39A-39D, 40A-40D, 41A-41E, or 42A-42D,e.g., the targeting domains of 24 or more nucleotides may comprise the 23-mer gRNAs described in

Tables 37A-37D, 38A-38E, 39A-39D, 40A-40D, 41A-41E, or 42A-42D. Targeting domains, disclosed herein, may comprises the 24-mer described in Tables 37A-37D, 38A-38E, 39A-39D,

146

5535.1 40A-40D, 41A-41E, or 42A-42D, e.g., the targeting domains of 25 or more nucleotides may comprise the 24-mer gRNAs described in Tables 37A-37D, 38A-38E, 39A-39D, 40A-40D,

41A-41E, or 42A-42D. gRNAs were identified for both single-gRNA nuclease cleavage and for a dual-gRNA paired "nickase" strategy. Criteria for selecting gRNAs and the determination for which gRNAs can be used for the dual-gRNA paired "nickase" strategy is based on two considerations:

1. gRNA pairs should be oriented on the DNA such that PAMs are facing out and

cutting with the D10A Cas9 nickase will result in 5' overhangs.

2. An assumption that cleaving with dual nickase pairs will result in deletion of the entire intervening sequence at a reasonable frequency. However, cleaving with dual nickase pairs can also result in indel mutations at the site of only one of the gRNAs. Candidate pair members can be tested for how efficiently they remove the entire sequence versus causing indel mutations at the site of one gRNA.

The targeting domains discussed herein can be incorporated into the gRNAs described herein.

In an embodiment, gRNAs were identified and ranked into 4 tiers for S. pyogenes

(Tables 37A-37D or 40A-40D), and N. meningitidis (Tables 39A-39D or 42A-42D); and 4 tiers for S. aureus (Tables 38A-38E or 41A-41E). For S. pyogenes, and N. meningitidis, the targeting domain for tier 1 gRNA molecules were selected based on (1) target position, e.g., intron 2 or intron 10, (2) a high level of orthogonality and (3) the presence of 5'G. The targeting domain for tier 2 gRNA molecules were selected based on (1) target position, e.g., intron 2 or intron 10 and (2) a high level of orthogonality. The targeting domain for tier 3 gRNA molecules were selected based on (1) target position, e.g., intron 2 or intron 10 and (2) the presence of 5'G. The targeting domain for tier 4 gRNA molecules were selected based on target position, e.g., intron 2 or intron 10. For S. aureus, the targeting domain for tier 1 gRNA molecules were selected based on (1) target position, e.g., intron 2 or intron 10, (2) a high level of orthogonality, (3) the presence of 5'G and (4) PAM is NNGRRT. The targeting domain for tier 2 gRNA molecules were selected based on (1) target position, e.g., intron 2 or intron 10, (2) a high level of orthogonality, and (3) PAM is NNGRRT. The targeting domain for tier 3 gRNA molecules were selected based on (1) target position, e.g., intron 2 or intron 10, (2) the presence of a 5'G and (2) PAM is NNGRRT. The targeting domain for tier 4 gRNA molecules were selected based on (1) target position, e.g., intron 2 or intron 10 and (2) PAM is NNGRRT. The targeting domain for tier 5 gRNA molecules

147

5535.1 were selected based on (1) (1) target position, e.g., intron 2 or intron 10 and (2) PAM is

NNGRRV. Note that tiers are non-inclusive (each gRNA is listed only once for the strategy). In certain instances, no gRNA was identified based on the criteria of the particular tier.

In an embodiment, two or more (e.g., three or four) gRNA molecules are used with one Cas9 molecule. In another embodiment, when two or more (e.g., three or four) gRNAs are used with two or more Cas9 molecules, at least one Cas9 molecule is from a different species than the other Cas9 molecule(s). For example, when two gRNA molecules are used with two Cas9 molecules, one Cas9 molecule can be from one species and the other Cas9 molecule can be from a different species. Both Cas9 species are used to generate a single or double-strand break, as desired.

Any of the targeting domains in the tables described herein can be used with a Cas9 nickase molecule to generate a single strand break.

Any of the targeting domains in the tables described herein can be used with a Cas9 nuclease molecule to generate a double strand break.

When two gRNAs designed for use to target two Cas9 molecules, one Cas9 can be one species, the second Cas9 can be from a different species. Both Cas9 species are used to generate a single or double- strand break, as desired.

It is contemplated herein that any upstream gRNA described herein may be paired with any downstream gRNA described herein. When an upstream gRNA designed for use with one species of Cas9 is paired with a downstream gRNA designed for use from a different species of Cas9, both Cas9 species are used to generate a single or double-strand break, as desired.

Exemplary Targeting Domains

Table 1A provides exemplary targeting domains for the F508del target position in the CFTR gene selected according to the first tier parameters. The targeting domains are selected based on close proximity to mutation and orthogonality in the human genome. It is contemplated herein that the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. pyogenes Cas9 molecule that gives double stranded cleavage. Any of the targeting domains in the table can be used with a S. pyogenes Cas9 single- stranded break nucleases (nickases). In an embodiment, dual targeting is used to create two nicks on opposite DNA strands by using S. pyogenes Cas9 nickases with

148

5535.1 two targeting domains that are complementary to opposite DNA strands, e.g., a gRNA comprising any minus strand targeting domain may be paired any gRNA comprising a plus strand targeting domain provided that the two gRNAs are oriented on the DNA such that PAMs face outward and the distance between the 5' ends of the gRNAs is 0-50bp. In an embodiment, two 17-mer RNAs are used to target two Cas9 nucleases or two Cas9 nickases, e.g., CFTR-18 and CFTR- 16 are used.

Table 1A

Table IB provides exemplary targeting domains for the F508del target position in the CFTR gene selected according to the second tier parameters. The targeting domains are selected based on the presence of a 5' G and reasonable proximity to mutation. It is contemplated herein that the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. pyogenes Cas9 molecule that gives double stranded cleavage. Any of the targeting domains in the table can be used with a S. pyogenes Cas9 single- stranded break nucleases (nickases). In an embodiment, dual targeting is used to create two nicks on opposite DNA strands by using S. pyogenes Cas9 nickases with two targeting domains that are complementary to opposite DNA strands, e.g., a gRNA comprising any minus strand targeting domain may be paired any gRNA comprising a plus strand targeting domain provided that the two gRNAs are oriented on the DNA such that PAMs face outward and the distance between the 5' ends of the gRNAs is 0-50bp.

Table IB

149

5535.1 CFT -24 - GAUAAUGACCUAAUAAUGAU 20 395

CFTR-29 - GGGAGAACUGGAGCCUUCAG 20 396

CFTR-30 - GGAGAACUGGAGCCUUCAGA 20 397

CFTR-37 + GUAGACUAACCGAUUGAAUA 20 398

CFTR-44 + GUCAUUAUCAAAUCACGCUC 20 399

CFTR-50 - GGUGAUUAUGGGAGAAC 17 400

CFTR-52 - GAACUGGAGCCUUCAGA 17 401

CFTR-57 - GGGUAAGCUACUGUGAA 17 402

CFTR-59 + G ACU AACCG AU UG AAU A 17 403

CFTR-60 + GAGCCAAAUAUAUAAUU 17 404

Table 1C provides exemplary targeting domains for the F508del target position in the CFTR gene selected according to the third tier parameters. The targeting domains are selected based on reasonable proximity to mutation. It is contemplated herein that the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. pyogenes Cas9 molecule that gives double stranded cleavage. Any of the targeting domains in the table can be used with a S. pyogenes Cas9 single- stranded break nucleases (nickases). In an embodiment, dual targeting is used to create two nicks on opposite DNA strands by using S. pyogenes Cas9 nickases with two targeting domains that are complementary to opposite DNA strands, e.g., a gRNA comprising any minus strand targeting domain may be paired any gRNA comprising a plus strand targeting domain provided that the two gRNAs are oriented on the DNA such that PAMs face outward and the distance between the 5' ends of the gRNAs is 0-50bp.

Table 1C

150

5535.1 CFT -13 - UCUGUUCUCAGUUUUCC 17 413

CFTR-14 - UUUUCCUGGAUUAUGCC 17 414

CFTR-15 - AAAGAAAAUAUCAUCUU 17 415

CFTR-16 - AGCAUGCCAACUAGAAG 17 391

CFTR-17 + UUCUUACCUCUUCUAGU 17 416

CFTR-20 + UUUUCUUUAAUGGUGCC 17 417

CFTR-22 + UUAAUUUUACCCUCUGA 17 418

CFTR-23 - UGAUAAUGACCUAAUAAUGA 20 419

CFTR-25 - UUUCCAGACUUCACUUCUAA 20 420

CFTR-26 - UUCACUUCUAAUGGUGAUUA 20 421

CFTR-27 - UCACUUCUAAUGGUGAUUAU 20 422

CFTR-28 - AAUGGUGAUUAUGGGAGAAC 20 423

CFTR-31 - CACUACCCAAAUUAUAUAUU 20 424

CFTR-32 - UAUUUGGCUCCAUAUUCAAU 20 425

CFTR-33 - AUAUAUUUAUGUUUCCUCUA 20 426

CFTR-34 - UAUAUUUAUGUUUCCUCUAU 20 427

CFTR-35 - UAUGGGUAAGCUACUGUGAA 20 428

CFTR-36 + UCACAGUAGCUUACCCAUAG 20 429

CFTR-38 + AUGG AGCCAAAU AU AU AAU U 20 430

CFTR-39 + UGGAGCCAAAUAUAUAAUUU 20 431

CFTR-40 + AUAUAAUUUGGGUAGUGUGA 20 432

CFTR-41 + UAUAAUUUGGGUAGUGUGAA 20 433

CFTR-42 + UCACCAU U AG AAG UG AAG UC 20 434

CFTR-43 + AAAUAAAACCCAUCAUUAUU 20 435

CFTR-45 - UAAUGACCUAAUAAUGA 17 436

CFTR-46 - AAUGACCUAAUAAUGAU 17 437

CFTR-47 - CCAGACUUCACUUCUAA 17 438

CFTR-48 - ACUUCUAAUGGUGAUUA 17 439

CFTR-49 - CUUCUAAUGGUGAUUAU 17 440

CFTR-51 - AGAACUGGAGCCUUCAG 17 441

CFTR-53 - UACCCAAAUUAUAUAUU 17 442

CFTR-54 - UUGGCUCCAUAUUCAAU 17 443

CFTR-55 - UAUUUAUGUUUCCUCUA 17 444

CFTR-56 - AUUUAUGUUUCCUCUAU 17 445

CFTR-58 + CAGUAGCUUACCCAUAG 17 446

CFTR-61 + AGCCAAAU AUAUAAUUU 17 447

CFTR-62 + UAAUUUGGGUAGUGUGA 17 448

CFTR-63 + AAUUUGGGUAGUGUGAA 17 449

CFTR-64 + CCAUUAGAAGUGAAGUC 17 450

CFTR-65 + UAAAACCCAUCAUUAUU 17 451

CFTR-66 + AUUAUCAAAUCACGCUC 17 452

151

5535.1 Table ID provides exemplary targeting domains for the F508del target position in the CFTR gene selected based on reasonable proximity to mutation. It is contemplated herein that the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. aureus Cas9 molecule that gives double stranded cleavage. Any of the targeting domains in the table can be used with a S. aureus Cas9 single- stranded break nucleases (nickases). In an embodiment, dual targeting is used to create two nicks on opposite DNA strands by using S. aureus Cas9 nickases with two targeting domains that are complementary to opposite DNA strands, e.g., a gRNA comprising any minus strand targeting domain may be paired any gRNA comprising a plus strand targeting domain provided that the two gRNAs are oriented on the DNA such that PAMs face outward and the distance between the 5' ends of the gRNAs is 0-50bp.

Table ID

152

5535.1 CFT -134 - UCCUCUAUGGGUAAGCUACU 20 674

CFTR-135 - CUAUGGGUAAGCUACUGUGA 20 675

CFTR-136 + GGUCAUUAUCAAAUCACGCU 20 676

CFTR-42 + UCACCAUUAGAAGUGAAGUC 20 434

CFTR-138 + AU CACC AU U AG AAG UG AAG U 20 677

CFTR-139 + UCCCAUAAUCACCAUUAGAA 20 678

CFTR-140 + AGUUCUCCCAUAAUCACCAU 20 679

CFTR-141 + ACUGUGCUUAAUUUUACCCU 20 680

CFTR-142 + CCAGGAAAACUGAGAACAGA 20 681

CFTR-143 + UAAUCCAGGAAAACUGAGAA 20 682

CFTR-144 + AGGCAUAAUCCAGGAAAACU 20 683

CFTR-145 + CCAGGCAUAAUCCAGGAAAA 20 684

CFTR-10 + AAUGGUGCCAGGCAUAAUCC 20 389

CFTR-147 + UAAUGGUGCCAGGCAUAAUC 20 685

CFTR-7 + UCUGUAUCUAUAUUCAUCAU 20 409

CFTR-149 + UUCUGUAUCUAUAUUCAUCA 20 686

CFTR-150 + UAUAUAAUUUGGGUAGUGUG 20 687

CFTR-151 + AAAUAUAUAAUUUGGGUAGU 20 688

CFTR-152 + UAUGGAGCCAAAUAUAUAAU 20 689

CFTR-37 + GUAGACUAACCGAUUGAAUA 20 398

CFTR-154 + UGUAGACUAACCGAUUGAAU 20 690

CFTR-155 + AAUAUAUGUAGACUAACCGA 20 691

CFTR-36 + UCACAGUAGCUUACCCAUAG 20 429

CFTR-157 + U UCACAG U AGCU U ACCCAU A 20 692

CFTR-158 + CAUUCACAGUAGCUUACCCA 20 693

CFTR-159 - UUGGAGGCAAGUGAAUC 17 694

CFTR-160 - AUAAUGACCUAAUAAUG 17 695

CFTR-161 - CACUUCUAAUGGUGAUU 17 696

CFTR-48 - ACUUCUAAUGGUGAUUA 17 439

CFTR-49 - CUUCUAAUGGUGAUUAU 17 440

CFTR-164 - UCUAAUGGUGAUUAUGG 17 697

CFTR-165 - UGGUGAUUAUGGGAGAA 17 698

CFTR-50 - GGUGAUUAUGGGAGAAC 17 400

CFTR-167 - GGGAGAACUGGAGCCUU 17 699

CFTR-168 - GAGAACUGGAGCCUUCA 17 700

CFTR-169 - GGGUAAAAUUAAGCACA 17 701

CFTR-12 - GGUAAAAUUAAGCACAG 17 390

CFTR-171 - AA AA U U AAG C AC AG U G G 17 702

CFTR-172 - UUCUGUUCUCAGUUUUC 17 703

CFTR-173 - UAUGCCUGGCACCAUUA 17 704

CFTR-174 - CUUUGGUGUUUCCUAUG 17 705

CFTR-175 - UAUGAUGAAUAUAGAUA 17 706

CFTR-176 - C A U C AA AG CAUGCCAAC 17 707

153

5535.1 CFT -177 - CAAAGCAUGCCAACUAG 17 708

CFTR-178 - UGCCAACUAGAAGAGGU 17 709

CFTR-179 - AAGAGGUAAGAAACUAU 17 710

CFTR-180 - ACUUUUUGAUUAUGCAU 17 711

CFTR-181 - AUAUUUAUGUUUCCUCU 17 712

CFTR-182 - UCUAUGGGUAAGCUACU 17 713

CFTR-183 - UGGGUAAGCUACUGUGA 17 714

CFTR-184 + CAUUAUCAAAUCACGCU 17 715

CFTR-64 + CCAUUAGAAGUGAAGUC 17 450

CFTR-186 + ACCAUUAGAAGUGAAGU 17 716

CFTR-187 + CAUAAUCACCAUUAGAA 17 717

CFTR-188 + UCUCCCAUAAUCACCAU 17 718

CFTR-189 + GUGCUUAAUUUUACCCU 17 719

CFTR-190 + GGAAAACUGAGAACAGA 17 720

CFTR-191 + UCCAGGAAAACUGAGAA 17 721

CFTR-192 + CAUAAUCCAGGAAAACU 17 722

CFTR-193 + GGCAUAAUCCAGGAAAA 17 723

CFTR-21 + GGUGCCAGGCAUAAUCC 17 394

CFTR-195 + UGGUGCCAGGCAUAAUC 17 724

CFTR-18 + GUAUCUAUAUUCAUCAU 17 392

CFTR-197 + UGUAUCUAUAUUCAUCA 17 725

CFTR-198 + AUAAUUUGGGUAGUGUG 17 726

CFTR-199 + UAUAUAAUUUGGGUAGU 17 727

CFTR-200 + GGAGCCAAAUAUAUAAU 17 728

CFTR-59 + GACUAACCGAUUGAAUA 17 403

CFTR-202 + AG ACU AACCG AU UGAAU 17 729

CFTR-203 + AUAUGUAGACUAACCGA 17 730

CFTR-58 + CAGUAGCUUACCCAUAG 17 446

CFTR-205 + ACAGUAGCUUACCCAUA 17 731

CFTR-206 + UCACAGUAGCUUACCCA 17 732

Table IE provides exemplary targeting domains for the F508del target position in the CFTR gene selected based on reasonable proximity to mutation. It is contemplated herein that the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a N. meningitidis Cas9 molecule that gives

154

5535.1 double stranded cleavage. Any of the targeting domains in the table can be used with a N.

meningitidis Cas9 single- stranded break nucleases (nickases). In an embodiment, dual targeting is used to create two nicks on opposite DNA strands by using N. meningitidis Cas9 nickases with two targeting domains that are complementary to opposite DNA strands, e.g., a gRNA comprising any minus strand targeting domain may be paired any gRNA comprising a plus strand targeting domain provided that the two gRNAs are oriented on the DNA such that PAMs face outward and the distance between the 5' ends of the gRNAs is 0-50bp.

Table IE

Table 2A provides exemplary targeting domains for the G551D target position in the

CFTR gene selected according to the first tier parameters. The targeting domains are selected based close proximity to mutation and orthogonality in the human genome. It is contemplated herein that the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. pyogenes Cas9 molecule that gives double stranded cleavage. Any of the targeting domains in the table can be used with a S. pyogenes Cas9 single- stranded break nucleases (nickases). In an embodiment, dual targeting is used to create two nicks on opposite DNA strands by using S. pyogenes Cas9 nickases with two targeting domains that are complementary to opposite DNA strands, e.g., a gRNA comprising any minus strand targeting domain may be paired any gRNA comprising a plus

155

5535.1 strand targeting domain provided that the two gRNAs are oriented on the DNA such that PAMs face outward and the distance between the 5' ends of the gRNAs is 0-50bp.

Table 2A

Table 2B provides exemplary targeting domains for the G551D target position in the CFTR gene selected according to the second tier parameters. The targeting domains are selected based on the presence of a 5' G and reasonable proximity to mutation. It is contemplated herein that the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. pyogenes Cas9 molecule that gives double stranded cleavage. Any of the targeting domains in the table can be used with a S. pyogenes Cas9 single- stranded break nucleases (nickases). In an embodiment, dual targeting is used to create two nicks on opposite DNA strands by using S. pyogenes Cas9 nickases with two targeting domains that are complementary to opposite DNA strands, e.g., a gRNA comprising any minus strand targeting domain may be paired any gRNA comprising a plus strand targeting domain provided that the two gRNAs are oriented on the DNA such that PAMs face outward and the distance between the 5' ends of the gRNAs is 0-50bp.

Table 2B

156

5535.1 CFT -102 - GGAAUUGAAAAAAUCCU 17 467

CFTR-103 - GAAUUGAAAAAAUCCUG 17 468

CFTR-109 + GUCUUUCUCUGCAAACU 17 469

Table 2C provides exemplary targeting domains for the G551D target position in the CFTR gene selected according to the third tier parameters. The targeting domains are selected based on reasonable proximity to mutation. It is contemplated herein that the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. pyogenes Cas9 molecule that gives double stranded cleavage. Any of the targeting domains in the table can be used with a S. pyogenes Cas9 single- stranded break nucleases (nickases). In an embodiment, dual targeting is used to create two nicks on opposite DNA strands by using S. pyogenes Cas9 nickases with two targeting domains that are complementary to opposite DNA strands, e.g., a gRNA comprising any minus strand targeting domain may be paired any gRNA comprising a plus strand targeting domain provided that the two gRNAs are oriented on the DNA such that PAMs face outward and the distance between the 5' ends of the gRNAs is 0-50bp.

Table 2C

157

5535.1 CFT -93 - AAAGACAAUAUAGUUCU 17 488

CFTR-94 - AAUAUAGUUCUUGGAGA 17 489

CFTR-95 - AUAGUUCUUGGAGAAGG 17 490

CFTR-98 - CAAGAAUU UCU U UAGCA 17 491

CFTR-101 - UGGAAUUGAAAAAAUCC 17 492

CFTR-104 - AAAAUCCUGGGGUUUUA 17 493

CFTR-105 - UGGGGUUUUAUGGCUAG 17 494

CFTR-107 - UUAAGAACUAUAAAUAA 17 495

CFTR-110 + CUCAAUCUGAAUUUGAA 17 496

Table 2D provides exemplary targeting domains for the G551D target position in the CFTR gene selected based on reasonable proximity to mutation. It is contemplated herein that the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. aureus Cas9 molecule that gives double stranded cleavage. Any of the targeting domains in the table can be used with a S. aureus Cas9 single- stranded break nucleases (nickases). In an embodiment, dual targeting is used to create two nicks on opposite DNA strands by using S. aureus Cas9 nickases with two targeting domains that are complementary to opposite DNA strands, e.g., a gRNA comprising any minus strand targeting domain may be paired any gRNA comprising a plus strand targeting domain provided that the two gRNAs are oriented on the DNA such that PAMs face outward and the distance between the 5' ends of the gRNAs is 0-50bp.

Table 2D

158

5535.1 CFT -232 - AGAAGGUGGAAUCACACUGA 20 743

CFTR-74 - GAAGGUGGAAUCACACUGAG 20 461

CFTR-234 - AUCACACUGAGUGGAGGUCA 20 744

CFTR-235 - CUGAGUGGAGGUCAACGAGC 20 745

CFTR-236 - GCAAGAAUUUCUUUAGCAAG 20 746

CFTR-237 - UAUUGCUUUAUAUUCUGUUU 20 747

CFTR-78 - AUUGCUUUAUAUUCUGUUUC 20 476

CFTR-239 - UUUAUAUUCUGUUUCUGGAA 20 748

CFTR-240 - UUUCUGGAAUUGAAAAAAUC 20 749

CFTR-79 - U UCUGGAAU UG AAAAAAUCC 20 477

CFTR-242 - AUCCUGGGGUUUUAUGGCUA 20 750

CFTR-243 - GGUUUUAUGGCUAGUGGGUU 20 751

CFTR-244 - GUGGGUUAAGAAUCACAUUU 20 752

CFTR-245 + CUUUAACCACAGUUGAAAUU 20 753

CFTR-246 + CACUAUUGCUUUAACCACAG 20 754

CFTR-247 + UUAGUAUGCUCAAUCUGAAU 20 755

CFTR-248 + UCACUUUUAGUAUGCUCAAU 20 756

CFTR-249 + UUACCAAAAAUAGAAAAUUA 20 757

CFTR-250 + U AU U ACCAAAAAU AG AAAAU 20 758

CFTR-251 + AGAUGUCCUAUUACCAAAAA 20 759

CFTR-87 + AUUGUCUUUCUCUGCAAACU 20 483

CFTR-253 + UAUUGUCUUUCUCUGCAAAC 20 760

CFTR-254 + AGUGUGAUUCCACCUUCUCC 20 761

CFTR-255 + AUUAGUUAUUCACCUUGCUA 20 762

CFTR-256 + AAUGUCUGUAAUUUUUUUAC 20 763

CFTR-257 + AAACAGAAUAUAAAGCAAUA 20 764

CFTR-258 + AGAAACAGAAUAUAAAGCAA 20 765

CFTR-259 + GAUUUUUU CAAU U CC AG AAA 20 766

CFTR-260 + CCCCAGGAUUUUUUCAAUUC 20 767

CFTR-261 - GUGAUAUAUGAUUACAU 17 768

CFTR-262 - AUAUAUGAUUACAUUAG 17 769

CFTR-90 - UAUAUGAUUACAUUAGA 17 485

159

5535.1 CFT -264 - UGCCU U UCAAAU UCAGA 17 770

CFTR-265 - UUUUCUAUUUUUGGUAA 17 771

CFTR-266 - GGACAUCUCCAAGUUUG 17 772

CFTR-267 - ACAUCUCCAAGUUUGCA 17 773

CFTR-268 - GAAAGACAAUAUAGUUC 17 774

CFTR-93 - AAAGACAAUAUAGUUCU 17 488

CFTR-270 - AGACAAUAUAGUUCUUG 17 775

CFTR-271 - UAUAGUUCUUGGAGAAG 17 776

CFTR-95 - AUAGUUCUUGGAGAAGG 17 490

CFTR-273 - GAGAAGGUGGAAUCACA 17 777

CFTR-274 - AGGUGGAAUCACACUGA 17 778

CFTR-96 - GGUGGAAUCACACUGAG 17 456

CFTR-276 - ACACUGAGUGGAGGUCA 17 779

CFTR-277 - AGUGGAGGUCAACGAGC 17 780

CFTR-278 - AGAAUUUCUUUAGCAAG 17 781

CFTR-279 - UGCUUUAUAUUCUGUUU 17 782

CFTR-100 - GCUUUAUAUUCUGUUUC 17 466

CFTR-281 - AUAUUCUGUUUCUGGAA 17 783

CFTR-282 - CUGGAAUUGAAAAAAUC 17 784

CFTR-101 - UGGAAUUGAAAAAAUCC 17 492

CFTR-284 - CUGGGGUUUUAUGGCUA 17 785

CFTR-285 - UUUAUGGCUAGUGGGUU 17 786

CFTR-286 - GGUUAAGAAUCACAUUU 17 787

CFTR-287 + U AACC AC AG U U G A AA U U 17 788

CFTR-288 + U AU UGCU U U AACCACAG 17 789

CFTR-289 + GUAUGCUCAAUCUGAAU 17 790

CFTR-290 + CUUUUAGUAUGCUCAAU 17 791

CFTR-291 + CCAAAAAUAGAAAAUUA 17 792

CFTR-292 + UACCAAAAAUAGAAAAU 17 793

CFTR-293 + UGUCCUAUUACCAAAAA 17 794

CFTR-109 + GUCUUUCUCUGCAAACU 17 469

CFTR-295 + UGUCUUUCUCUGCAAAC 17 795

CFTR-296 + GUGAUUCCACCUUCUCC 17 796

CFTR-297 + AGUUAUUCACCUUGCUA 17 797

CFTR-298 + GUCUGUAAUUUUUUUAC 17 798

CFTR-299 + CAGAAUAUAAAGCAAUA 17 799

CFTR-300 + AACAGAAUAUAAAGCAA 17 800

CFTR-301 + U U U U U CAAU UCC AG AAA 17 801

CFTR-302 + CAGGAUUUUUUCAAUUC 17 802

160

5535.1 Table 2E provides exemplary targeting domains for the G551D target position in the CFTR gene selected based on reasonable proximity to mutation. It is contemplated herein that the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a N. meningitidis Cas9 molecule that gives double stranded cleavage. Any of the targeting domains in the table can be used with a N.

meningitidis Cas9 single- stranded break nucleases (nickases). In an embodiment, dual targeting is used to create two nicks on opposite DNA strands by using N. meningitidis Cas9 nickases with two targeting domains that are complementary to opposite DNA strands, e.g., a gRNA comprising any minus strand targeting domain may be paired any gRNA comprising a plus strand targeting domain provided that the two gRNAs are oriented on the DNA such that PAMs face outward and the distance between the 5' ends of the gRNAs is 0-50bp.

Table 2E

Table 3A provides exemplary targeting domains for knocking out the SCNN1A gene selected according to the first tier parameters. The targeting domains are selected based close proximity to start codon and orthogonality in the human genome. It is contemplated herein that the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. pyogenes Cas9 molecule that gives double stranded cleavage. Any of the targeting domains in the table can be used with a S.

pyogenes Cas9 single- stranded break nucleases (nickases). In an embodiment, dual targeting is used to create two nicks on opposite DNA strands by using S. pyogenes Cas9 nickases with two targeting domains that are complementary to opposite DNA strands, e.g., a gRNA comprising

161

5535.1 any minus strand targeting domain may be paired any gRNA comprising a plus strand targeting domain provided that the two gRNAs are oriented on the DNA such that PAMs face outward and the distance between the 5' ends of the gRNAs is 0-50bp. In an embodiment, two 20-mer RNAs are used to target two Cas9 nucleases or two Cas9 nickases, e.g., SCNNlA-78 and SCNNlA-9 are used.

Table 3A

Table 3B provides exemplary targeting domains for knocking out the SCNN1A gene selected according to the second tier parameters. The targeting domains are selected based on the presence of a 5' G and reasonable proximity to start codon. It is contemplated herein that the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. pyogenes Cas9 molecule that gives double stranded cleavage. Any of the targeting domains in the table can be used with a S.

pyogenes Cas9 single- stranded break nucleases (nickases). In an embodiment, dual targeting is used to create two nicks on opposite DNA strands by using S. pyogenes Cas9 nickases with two targeting domains that are complementary to opposite DNA strands, e.g., a gRNA comprising any minus strand targeting domain may be paired any gRNA comprising a plus strand targeting domain provided that the two gRNAs are oriented on the DNA such that PAMs face outward and the distance between the 5' ends of the gRNAs is 0-50bp. In an embodiment, two 20-mer RNAs are used to target two Cas9 nucleases or two Cas9 nickases, e.g., SCNNlA-78 and SCNNlA-9 are used.

Table 3B

162

5535.1 SCNNlA-7 - GGGGAACAAGCUGGAGGAGC 20 504

SCNNlA-10 - GUCCACUCCAGGGCUCAUGA 20 505

SCNNlA-14 - GGGGAACAAGCGUGAGGAGC 20 506

SCNNlA-15 - GGGAACAAGCGUGAGGAGCA 20 507

SCNNlA-16 - GGAACAAGCGUGAGGAGCAG 20 508

SCNNlA-19 - GGGGCUGGGCCCCGAACCUG 20 509

SCNNlA-21 - GGCGCCCCAGCAGCCCACGG 20 510

SCNNlA-22 - GCCCCAGCAGCCCACGGCGG 20 511

SCNNlA-24 - GCAGCCCACGGCGGAGGAGG 20 512

SCNNlA-31 - GUGCUGUGGCUCUGCACCUU 20 513

SCNNlA-32 - GCACCUUUGGCAUGAUGUAC 20 514

SCNNlA-33 - GGCAUGAUGUACUGGCAAUU 20 515

SCNNlA-36 + GUAGGGAUUGAGGGUGCAGA 20 516

SCNNlA-37 + GAGGGUGCAGAUGGUCACUG 20 517

SCNNlA-39 + GGGUGCAGAUGGUCACUGCG 20 518

SCNNlA-42 + GAGGUUGAUGUUGAGGCUGA 20 519

SCNNlA-44 + GGUUGAUGUUGAGGCUGACG 20 520

SCNNlA-47 + GAGCCACAGCACUGCCCAGA 20 521

SCNNlA-51 + GGUUGUGCUGGGAGCACACC 20 522

SCNNlA-56 + GCGGAUGGCGCCGUGGAUGG 20 523

SCNNlA-58 + GAACUCGAAGAGCUCUCGGU 20 524

SCNNlA-62 + GGAGCGGUGGAACUCGAUCA 20 525

SCNNlA-68 + GUGGGCUGCUGGGGCGCCGC 20 526

SCNNlA-71 + GCUGGGGCGCCGCAGGUUCG 20 527

SCNNlA-76 + GCCCUGGAGUGGACUGUGGA 20 528

SCNNlA-80 - GCCCAUACCAGGUCUCA 17 529

SCNNlA-85 - GGAGGGGAACAAGCUGG 17 530

SCNNlA-86 - GAACAAGCUGGAGGAGC 17 531

SCNNlA-92 - GAAGGGGAACAAGCGUG 17 532

SCNNlA-93 - GAACAAGCGUGAGGAGC 17 533

SCNNlA-96 - GCGUGAGGAGCAGGGGC 17 534

SCNNlA-98 - GCUGGGCCCCGAACCUG 17 535

SCNNlA-99 - GGCGCCCCAGCAGCCCA 17 536

SCNNlA-100 - GCCCCAGCAGCCCACGG 17 537

SCNNlA-102 - GCAGCCCACGGCGGAGG 17 538

SCNNlA-103 - GCCCACGGCGGAGGAGG 17 539

SCNNlA-106 - GCACAACCGCAUGAAGA 17 540

SCNNlA-107 - GCAUGAAGACGGCCUUC 17 541

SCNNlA-115 + GGGAUUGAGGGUGCAGA 17 542

SCNNlA-116 + GGUGCAGAUGGUCACUG 17 543

SCNNlA-117 + GUGCAGAUGGUCACUGC 17 544

SCNNlA-121 + GUUGAUGUUGAGGCUGA 17 545

SCNNlA-131 + GCUGGGAGCACACCAGG 17 546

163

5535.1 SCNNlA-132 + GGAGCACACCAGGCGGA 17 547

SCNNlA-134 + GCGGAUGGCGCCGUGGA 17 548

SCNNlA-135 + GAUGGCGCCGUGGAUGG 17 549

SCNNlA-139 + GCUCUCGGUAGGAGCGG 17 550

SCNNlA-141 + GCGGUGGAACUCGAUCA 17 551

SCNNlA-142 + GGCCUCCUCCUCCGCCG 17 552

SCNNlA-143 + GCCUCCUCCUCCGCCGU 17 553

SCNNlA-147 + GGCUGCUGGGGCGCCGC 17 554

SCNNlA-150 + GGGGCGCCGCAGGUUCG 17 555

Table 3C provides exemplary targeting domains for knocking out the SCNN1A gene selected according to the third tier parameters. The targeting domains are selected based on reasonable proximity to start codon. It is contemplated herein that the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. pyogenes Cas9 molecule that gives double stranded cleavage. Any of the targeting domains in the table can be used with a S. pyogenes Cas9 single- stranded break nucleases (nickases). In an embodiment, dual targeting is used to create two nicks on opposite DNA strands by using S. pyogenes Cas9 nickases with two targeting domains that are complementary to opposite DNA strands, e.g., a gRNA comprising any minus strand targeting domain may be paired any gRNA comprising a plus strand targeting domain provided that the two gRNAs are oriented on the DNA such that PAMs face outward and the distance between the 5' ends of the gRNAs is 0-50bp. In an embodiment, two 20-mer RNAs are used to target two Cas9 nucleases or two Cas9 nickases, e.g., SCNNlA-78 and SCNNlA-9 are used. Table 3C

164

5535.1 SCNNlA-23 - CCAGCAGCCCACGGCGGAGG 20 566

SCNNlA-25 - UGCAACAACACCACCAUCCA 20 567

SCNNlA-26 - CAUCCACGGCGCCAUCCGCC 20 568

SCNNlA-27 - CCAGCACAACCGCAUGAAGA 20 569

SCNNlA-28 - ACCGCAUGAAGACGGCCUUC 20 570

SCNNlA-29 - CCGCAUGAAGACGGCCUUCU 20 571

SCNNlA-30 - CGGCCUUCUGGGCAGUGCUG 20 572

SCNNlA-34 - UGGCAAUUCGGCCUGCUUUU 20 573

SCNNlA-35 - CCUCAACAUCAACCUCAACU 20 574

SCNNlA-38 + AGGGUGCAGAUGGUCACUGC 20 575

SCNNlA-40 + AGACGAGCUUGUCCGAGUUG 20 576

SCNNlA-41 + CCGAGUUGAGGUUGAUGUUG 20 577

SCNNlA-43 + AGGUUGAUGUUGAGGCUGAC 20 578

SCNNlA-45 + UGAAGUACUCUCCGAAAAGC 20 579

SCNNlA-46 + UUGCCAGUACAUCAUGCCAA 20 580

SCNNlA-48 + CCCAGAAGGCCGUCUUCAUG 20 581

SCNNlA-49 + CCGUCUUCAUGCGGUUGUGC 20 582

SCNNlA-50 + CGUCUUCAUGCGGUUGUGCU 20 583

SCNNlA-52 + UGUGCUGGGAGCACACCAGG 20 584

SCNNlA-53 + CUGGGAGCACACCAGGCGGA 20 585

SCNNlA-54 + ACACCAGGCGGAUGGCGCCG 20 586

SCNNlA-55 + CAGGCGGAUGGCGCCGUGGA 20 587

SCNNlA-57 + AGAAGAACUCGAAGAGCUCU 20 588

SCNNlA-59 + CGAAGAGCUCUCGGUAGGAG 20 589

SCNNlA-60 + AGAGCUCUCGGUAGGAGCGG 20 590

SCNNlA-61 + AGGAGCGGUGGAACUCGAUC 20 591

SCNNlA-63 + CAGGGCCUCCUCCUCCGCCG 20 592

SCNNlA-64 + AGGGCCUCCUCCUCCGCCGU 20 593

SCNNlA-65 + CCUCCUCCGCCGUGGGCUGC 20 594

SCNNlA-66 + CUCCUCCGCCGUGGGCUGCU 20 595

SCNNlA-67 + UCCUCCGCCGUGGGCUGCUG 20 596

SCNNlA-69 + CUGCUGGGGCGCCGCAGGUU 20 597

SCNNlA-70 + UGCUGGGGCGCCGCAGGUUC 20 598

SCNNlA-72 + UUGUUCCCCUUCAUGAGCCC 20 599

SCNNlA-73 + CCCCUUCAUGAGCCCUGGAG 20 600

SCNNlA-74 + AUGAGCCCUGGAGUGGACUG 20 601

SCNNlA-75 + AGCCCUGGAGUGGACUGUGG 20 602

SCNNlA-77 + UUGUUCCCCUCCAUGAGACC 20 603

SCNNlA-79 + CCCUCCAUGAGACCUGGUAU 20 604

SCNNlA-81 - CAUACCAGGUCUCAUGG 17 605

SCNNlA-83 - UACCAGGUCUCAUGGAG 17 606

SCNNlA-84 - CAUGGAGGGGAACAAGC 17 607

165

5535.1 SCNNlA-87 - CCUCCACAGUCCACUCC 17 608

SCNNlA-88 - CUCCACAGUCCACUCCA 17 609

SCNNlA-89 - CACUCCAGGGCUCAUGA 17 610

SCNNlA-90 - ACUCCAGGGCUCAUGAA 17 611

SCNNlA-91 - CUCCAGGGCUCAUGAAG 17 612

SCNNlA-94 - AACAAGCGUGAGGAGCA 17 613

SCNNlA-95 - ACAAGCGUGAGGAGCAG 17 614

SCNNlA-97 - CGUGAGGAGCAGGGGCU 17 615

SCNNlA-101 - CCAGCAGCCCACGGCGG 17 616

SCNNlA-104 - AACAAC ACCACC AU CC A 17 617

SCNNlA-105 - CCACGGCGCCAUCCGCC 17 618

SCNNlA-108 - CAUGAAGACGGCCUUCU 17 619

SCNNlA-109 - CCUUCUGGGCAGUGCUG 17 620

SCNNlA-110 - CUGUGGCUCUGCACCUU 17 621

SCNNlA-111 - CCUUUGGCAUGAUGUAC 17 622

SCNNlA-112 - AUGAUGUACUGGCAAUU 17 623

SCNNlA-113 - CAAUUCGGCCUGCUUUU 17 624

SCNNlA-114 - CAAC AU CAACCU CAAC U 17 625

SCNNlA-118 + UGCAGAUGGUCACUGCG 17 626

SCNNlA-119 + CGAGCUUGUCCGAGUUG 17 627

SCNNlA-120 + AGUUGAGGUUGAUGUUG 17 628

SCNNlA-122 + UUGAUGUUGAGGCUGAC 17 629

SCNNlA-123 + UGAUGUUGAGGCUGACG 17 630

SCNNlA-124 + AGUACUCUCCGAAAAGC 17 631

SCNNlA-125 + CCAGUACAUCAUGCCAA 17 632

SCNNlA-126 + CCACAGCACUGCCCAGA 17 633

SCNNlA-127 + AGAAGGCCGUCUUCAUG 17 634

SCNNlA-128 + UCUUCAUGCGGUUGUGC 17 635

SCNNlA-129 + CUUCAUGCGGUUGUGCU 17 636

SCNNlA-130 + UGUGCUGGGAGCACACC 17 637

SCNNlA-133 + CCAGGCGGAUGGCGCCG 17 638

SCNNlA-136 + AGAACUCGAAGAGCUCU 17 639

166

5535.1 SCNNlA-137 + CUCGAAGAGCUCUCGGU 17 640

SCNNlA-138 + AGAGCUCUCGGUAGGAG 17 641

SCNNlA-140 + AGCGGUGGAACUCGAUC 17 642

SCNNlA-144 + CCUCCGCCGUGGGCUGC 17 643

SCNNlA-145 + CUCCGCCGUGGGCUGCU 17 644

SCNNlA-146 + UCCGCCGUGGGCUGCUG 17 645

SCNNlA-148 + CUGGGGCGCCGCAGGUU 17 646

SCNNlA-149 + UGGGGCGCCGCAGGUUC 17 647

SCNNlA-151 + UUCCCCUUCAUGAGCCC 17 648

SCNNlA-152 + CUUCAUGAGCCCUGGAG 17 649

SCNNlA-153 + AGCCCUGGAGUGGACUG 17 650

SCNNlA-154 + CCUGGAGUGGACUGUGG 17 651

SCNNlA-155 + CUGGAGUGGACUGUGGA 17 652

SCNNlA-156 + UUCCCCUCCAUGAGACC 17 653

SCNNlA-158 + UCCAUGAGACCUGGUAU 17 654

Table 3D provides exemplary targeting domains for knocking out the SCNN1A gene selected based on reasonable proximity to the start codon. It is contemplated herein that the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. aureus Cas9 molecule that gives double stranded cleavage. Any of the targeting domains in the table can be used with a S. aureus Cas9 single- stranded break nucleases (nickases). In an embodiment, dual targeting is used to create two nicks on opposite DNA strands by using S. aureus Cas9 nickases with two targeting domains that are complementary to opposite DNA strands, e.g., a gRNA comprising any minus strand targeting domain may be paired any gRNA comprising a plus strand targeting domain provided that the two gRNAs are oriented on the DNA such that PAMs face outward and the distance between the 5' ends of the gRNAs is 0-50bp.

Table 3D

167

5535.1 SCNNlA-165 - GUCUCAUGGAGGGGAACAAG 20 805

SCNNlA-5 - UCUCAUGGAGGGGAACAAGC 20 557

SCNNlA-167 - UCAUGGAGGGGAACAAGCUG 20 806

SCNNlA-6 - CAUGGAGGGGAACAAGCUGG 20 558

SCNNlA-169 - AGGGGAACAAGCUGGAGGAG 20 807

SCNNlA-170 - UAGCCCUCCACAGUCCACUC 20 808

SCNNlA-171 - CACAGUCCACUCCAGGGCUC 20 809

SCNNlA-172 - AGUCCACUCCAGGGCUCAUG 20 810

SCNNlA-10 - GUCCACUCCAGGGCUCAUGA 20 505

SCNNlA-11 - UCCACUCCAGGGCUCAUGAA 20 560

SCNNlA-12 - CCACUCCAGGGCUCAUGAAG 20 561

SCNNlA-176 - GCUCAUGAAGGGGAACAAGC 20 811

SCNNlA-177 - UCAUGAAGGGGAACAAGCGU 20 812

SCNNlA-13 - CAUGAAGGGGAACAAGCGUG 20 562

SCNNlA-179 - AGGGGAACAAGCGUGAGGAG 20 813

SCNNlA-14 - GGGGAACAAGCGUGAGGAGC 20 506

SCNNlA-181 - ACAAGCGUGAGGAGCAGGGG 20 814

SCNNlA-182 - UGAGGAGCAGGGGCUGGGCC 20 815

SCNNlA-183 - CGGCGCCCCAGCAGCCCACG 20 816

SCNNlA-21 - GGCGCCCCAGCAGCCCACGG 20 510

SCNNlA-185 - CGCCCCAGCAGCCCACGGCG 20 817

SCNNlA-22 - GCCCCAGCAGCCCACGGCGG 20 511

SCNNlA-187 - CCCAGCAGCCCACGGCGGAG 20 818

SCNNlA-23 - CCAGCAGCCCACGGCGGAGG 20 566

SCNNlA-189 - GGCGGAGGAGGAGGCCCUGA 20 819

SCNNlA-190 - AUCGAGUUCCACCGCUCCUA 20 820

SCNNlA-191 - CGAGUUCCACCGCUCCUACC 20 821

SCNNlA-192 - CCGCUCCUACCGAGAGCUCU 20 822

SCNNlA-193 - UGUGCUCCCAGCACAACCGC 20 823

SCNNlA-194 - AACCGCAUGAAGACGGCCUU 20 824

SCNNlA-195 - CUGGCAAUUCGGCCUGCUUU 20 825

SCNNlA-34 - UGGCAAUUCGGCCUGCUUUU 20 573

SCNNlA-197 - GCAAUUCGGCCUGCUUUUCG 20 826

SCNNlA-198 - GCCUCAACAUCAACCUCAAC 20 827

SCNNlA-199 + UCCCCUCCAUGAGACCUGGU 20 828

SCNNlA-200 + CCUCCAGCUUGUUCCCCUCC 20 829

SCNNlA-201 + UGGAGUGGACUGUGGAGGGC 20 830

SCNNlA-202 + GAGCCCUGGAGUGGACUGUG 20 831

SCNNlA-74 + AUGAGCCCUGGAGUGGACUG 20 601

SCNNlA-204 + CAUGAGCCCUGGAGUGGACU 20 832

SCNNlA-205 + UCCCCUUCAUGAGCCCUGGA 20 833

SCNNlA-72 + UUGUUCCCCUUCAUGAGCCC 20 599

SCNNlA-207 + CUUGUUCCCCUUCAUGAGCC 20 834

168

5535.1 SCNNlA-208 + CCUCACGCUUGUUCCCCUUC 20 835

SCNNlA-69 + CUGCUGGGGCGCCGCAGGUU 20 597

SCNNlA-210 + GCUGCUGGGGCGCCGCAGGU 20 836

SCNNlA-65 + CCUCCUCCGCCGUGGGCUGC 20 594

SCNNlA-212 + UCCUCCUCCGCCGUGGGCUG 20 837

SCNNlA-213 + UCAGGGCCUCCUCCUCCGCC 20 838

SCNNlA-214 + UAGGAGCGGUGGAACUCGAU 20 839

SCNNlA-60 + AGAGCUCUCGGUAGGAGCGG 20 590

SCNNlA-216 + AAGAGCUCUCGGUAGGAGCG 20 840

SCNNlA-58 + GAACUCGAAGAGCUCUCGGU 20 524

SCNNlA-218 + AGAACUCGAAGAGCUCUCGG 20 841

SCNNlA-219 + U G U U G U U GC AG AAG AAC UCG 20 842

SCNNlA-220 + UGGUGUUGUUGCAGAAGAAC 20 843

SCNNlA-221 + GGAUGGUGGUGUUGUUGCAG 20 844

SCNNlA-222 + CGUGGAUGGUGGUGUUGUUG 20 845

SCNNlA-223 + CACACCAGGCGGAUGGCGCC 20 846

SCNNlA-224 + UUGUGCUGGGAGCACACCAG 20 847

SCNNlA-50 + CGUCUUCAUGCGGUUGUGCU 20 583

SCNNlA-49 + CCGUCUUCAUGCGGUUGUGC 20 582

SCNNlA-227 + GCCGUCUUCAUGCGGUUGUG 20 848

SCNNlA-228 + UGCAGAGCCACAGCACUGCC 20 849

SCNNlA-229 + AGUACAUCAUGCCAAAGGUG 20 850

SCNNlA-230 + AGUACUCUCCGAAAAGCAGG 20 851

SCNNlA-231 + CGGGGUAGCUGAAGUACUCU 20 852

SCNNlA-232 + UGUUGAGGCUGACGGGGUAG 20 853

SCNNlA-42 + GAGGUUGAUGUUGAGGCUGA 20 519

SCNNlA-234 + UGAGGUUGAUGUUGAGGCUG 20 854

SCNNlA-235 + UGUCCGAGUUGAGGUUGAUG 20 855

SCNNlA-236 + GGAAGACGAGCUUGUCCGAG 20 856

SCNNlA-237 + UGCGGGGAAGACGAGCUUGU 20 857

SCNNlA-238 + AGAUGGUCACUGCGGGGAAG 20 858

SCNNlA-39 + GGGUGCAGAUGGUCACUGCG 20 518

SCNNlA-38 + AGGGUGCAGAUGGUCACUGC 20 575

169

5535.1 SCNNlA-37 + GAGGGUGCAGAUGGUCACUG 20 517

SCNNlA-242 + UGAGGGUGCAGAUGGUCACU 20 859

SCNNlA-243 - AGCCCAUACCAGGUCUC 17 860

SCNNlA-80 - GCCCAUACCAGGUCUCA 17 529

SCNNlA-245 - CCAUACCAGGUCUCAUG 17 861

SCNNlA-81 - CAUACCAGGUCUCAUGG 17 605

SCNNlA-82 - AUACCAGGUCUCAUGGA 17 501

SCNNlA-83 - UACCAGGUCUCAUGGAG 17 606

SCNNlA-249 - UCAUGGAGGGGAACAAG 17 862

SCNNlA-84 - CAUGGAGGGGAACAAGC 17 607

SCNNlA-251 - UGGAGGGGAACAAGCUG 17 863

SCNNlA-85 - GGAGGGGAACAAGCUGG 17 530

SCNNlA-253 - GGAACAAGCUGGAGGAG 17 864

SCNNlA-254 - CCCUCCACAGUCCACUC 17 865

SCNNlA-255 - AGUCCACUCCAGGGCUC 17 866

SCNNlA-256 - CCACUCCAGGGCUCAUG 17 867

SCNNlA-89 - CACUCCAGGGCUCAUGA 17 610

SCNNlA-90 - ACUCCAGGGCUCAUGAA 17 611

SCNNlA-91 - CUCCAGGGCUCAUGAAG 17 612

SCNNlA-260 - CAUGAAGGGGAACAAGC 17 868

SCNNlA-261 - UGAAGGGGAACAAGCGU 17 869

SCNNlA-92 - GAAGGGGAACAAGCGUG 17 532

SCNNlA-263 - GGAACAAGCGUGAGGAG 17 870

SCNNlA-93 - GAACAAGCGUGAGGAGC 17 533

SCNNlA-265 - AGCGUGAGGAGCAGGGG 17 871

SCNNlA-266 - GGAGCAGGGGCUGGGCC 17 872

SCNNlA-267 - CGCCCCAGCAGCCCACG 17 873

SCNNlA-100 - GCCCCAGCAGCCCACGG 17 537

SCNNlA-269 - CCCAGCAGCCCACGGCG 17 874

SCNNlA-101 - CCAGCAGCCCACGGCGG 17 616

SCNNlA-271 - AGCAGCCCACGGCGGAG 17 875

SCNNlA-102 - GCAGCCCACGGCGGAGG 17 538

170

5535.1 SCNNlA-273 - GGAGGAGGAGGCCCUGA 17 876

SCNNlA-274 - GAGUUCCACCGCUCCUA 17 877

SCNNlA-275 - GUUCCACCGCUCCUACC 17 878

SCNNlA-276 - CUCCUACCGAGAGCUCU 17 879

SCNNlA-277 - GCUCCCAGCACAACCGC 17 880

SCNNlA-278 - CGCAUGAAGACGGCCUU 17 881

SCNNlA-279 - GCAAUUCGGCCUGCUUU 17 882

SCNNlA-113 - CAAUUCGGCCUGCUUUU 17 624

SCNNlA-281 - AUUCGGCCUGCUUUUCG 17 883

SCNNlA-282 - U CAAC AU CAACCU CAAC 17 884

SCNNlA-283 + CCUCCAUGAGACCUGGU 17 885

SCNNlA-284 + CCAGCUUGUUCCCCUCC 17 886

SCNNlA-285 + AGUGGACUGUGGAGGGC 17 887

SCNNlA-286 + CCCUGGAGUGGACUGUG 17 888

SCNNlA-153 + AGCCCUGGAGUGGACUG 17 650

SCNNlA-288 + GAGCCCUGGAGUGGACU 17 889

SCNNlA-289 + CCUUCAUGAGCCCUGGA 17 890

SCNNlA-151 + UUCCCCUUCAUGAGCCC 17 648

SCNNlA-291 + GUUCCCCUUCAUGAGCC 17 891

SCNNlA-292 + CACGCUUGUUCCCCUUC 17 892

SCNNlA-148 + CUGGGGCGCCGCAGGUU 17 646

SCNNlA-294 + GCUGGGGCGCCGCAGGU 17 893

SCNNlA-144 + CCUCCGCCGUGGGCUGC 17 643

SCNNlA-296 + UCCUCCGCCGUGGGCUG 17 894

SCNNlA-297 + GGGCCUCCUCCUCCGCC 17 895

SCNNlA-298 + GAGCGGUGGAACUCGAU 17 896

SCNNlA-139 + GCUCUCGGUAGGAGCGG 17 550

SCNNlA-300 + AGCUCUCGGUAGGAGCG 17 897

SCNNlA-137 + CUCGAAGAGCUCUCGGU 17 640

SCNNlA-302 + ACUCGAAGAGCUCUCGG 17 898

SCNNlA-303 + UGUUGCAGAAGAACUCG 17 899

SCNNlA-304 + U G U U G U U GC AG AAG AAC 17 900

171

5535.1 SCNNlA-305 + UGGUGGUGUUGUUGCAG 17 901

SCNNlA-306 + GGAUGGUGGUGUUGUUG 17 902

SCNNlA-307 + ACCAGGCGGAUGGCGCC 17 903

SCNNlA-308 + U G C U G G G AG C AC ACC AG 17 904

SCNNlA-129 + CUUCAUGCGGUUGUGCU 17 636

SCNNlA-128 + UCUUCAUGCGGUUGUGC 17 635

SCNNlA-311 + GUCUUCAUGCGGUUGUG 17 905

SCNNlA-312 + AGAGCCACAGCACUGCC 17 906

SCNNlA-313 + ACAUCAUGCCAAAGGUG 17 907

SCNNlA-314 + ACUCUCCGAAAAGCAGG 17 908

SCNNlA-315 + GGUAGCUGAAGUACUCU 17 909

SCNNlA-316 + UGAGGCUGACGGGGUAG 17 910

SCNNlA-121 + GUUGAUGUUGAGGCUGA 17 545

SCNNlA-318 + GGUUGAUGUUGAGGCUG 17 911

SCNNlA-319 + CCGAGUUGAGGUUGAUG 17 912

SCNNlA-320 + AGACGAGCUUGUCCGAG 17 913

SCNNlA-321 + GGGGAAGACGAGCUUGU 17 914

SCNNlA-322 + UGGUCACUGCGGGGAAG 17 915

SCNNlA-118 + UGCAGAUGGUCACUGCG 17 626

SCNNlA-117 + GUGCAGAUGGUCACUGC 17 544

SCNNlA-116 + GGUGCAGAUGGUCACUG 17 543

SCNNlA-326 + GGGUGCAGAUGGUCACU 17 916

Table 4A provides exemplary targeting domains for correcting a mutation (e.g., 2789+5G) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., 2789+5G), have a high level of orthogonality and start with a 5'G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 4A

172

5535.1 CFTR-2789-3 - GAAUUUAGAUGUGGGCA 17 939

CFTR-2789-4 - GUGUCUUGU UCCAUUCC 17 940

CFTR-2789-5 - GUGGGCAUGGGAGGAAU 17 941

CFTR-2789-6 - GUUGUGCUG UGGCUCCU 17 942

CFTR-2789-7 - GAUGUGAAUUUAGAUGU 17 943

CFTR-2789-8 - GACCCAGGAACACAAAGCAA 20 944

CFTR-2789-9 + GUGUCACCUCACCCAACUAA 20 945

CFTR-2789-10 - GUGUCUUGU UCCAUUCCAGG 20 946

CFTR-2789-11 - GAUGUGGGCAUGGGAGGAAU 20 947

CFTR-2789-12 - GUGAAU UUAGAUGUGGGCAU 20 948

Table 4B provides exemplary targeting domains for correcting a mutation (e.g., 2789+5G) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., 2789+5G) and have a high level of orthogonality. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 4B

173

5535.1 CFTR-2789-30 - CCAGGUGGCUGCUUCU U 17 966

CFTR-2789-31 - AU AU UGG U ACACACAU CAAA 20 967

CFTR-2789-32 + A A AG AAGCAGCCACCUGGAA 20 968

CFTR-2789-33 + ACAAUCUACACAAUAGGACA 20 969

CFTR-2789-34 - UGUGAAUUUAGAUGUGGGCA 20 970

CFTR-2789-35 + UGAUGUGUGUACCAAUAUCA 20 971

CFTR-2789-36 - AUUAUGGUAGUGGAAAGAUA 20 972

CFTR-2789-37 - UUCAUUUCUCCCAAGCAUUA 20 973

CFTR-2789-38 + CAACCAAAGAAGCAGCCACC 20 974

CFTR-2789-39 - ACUGUGUCU UGUUCCAUUCC 20 975

CFTR-2789-40 + CUUCCU UUGCU UUGUGUUCC 20 976

CFTR-2789-41 + UACAAUACAUACAAACAUAG 20 977

CFTR-2789-42 - UCUCCCAAGCAUUAUGGUAG 20 978

CFTR-2789-43 - AAUUUAGAUGUGGGCAUGGG 20 979

CFTR-2789-44 - CUGCUUCUUUGGU UGUGCUG 20 980

CFTR-2789-45 - UGAUGACCAUUAGUUGGGUG 20 981

CFTR-2789-46 - AAUUGUGUGUACCUUGAUAU 20 982

CFTR-2789-47 - UUGGUUGUGCUGUGGCUCCU 20 983

CFTR-2789-48 + CUUUCCACUACCAUAAUGCU 20 984

CFTR-2789-49 - UUUAAAUGAUGACCAUUAGU 20 985

CFTR-2789-50 - UGUGAUGUGAAUUUAGAUGU 20 986

CFTR-2789-51 + UUUCCACUACCAUAAUGCUU 20 987

CFTR-2789-52 - AUUCCAGGUGGCUGCU UCUU 20 988

CFTR-2789-53 - UUAAAUGAUGACCAUUAGUU 20 989

Table 4C provides exemplary targeting domains for correcting a mutation (e.g., 2789+5G) in the CFTR gene selected according to the third tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., 2789+5G) and start with a 5'G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 4C

174

5535.1 Table 4D provides exemplary targeting domains for correcting a mutation (e.g., 2789+5G) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., 2789+5G). It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase). Table 4D

Table 5A provides exemplary targeting domains for correcting a mutation (e.g.,

2789+5G) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., 2789+5G), have a high level of orthogonality, start with a 5'G, and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 5A

175

5535.1 Length

CFTR-2789-71 + G AU U ACAAU ACAU ACAAACAU A 22 1007

CFTR-2789-72 + GGAUUACAAUACAUACAAACAUA 23 1008

CFTR-2789-73 - GCUGUGGCUCCUUGGAAA 18 1009

CFTR-2789-74 - GUGCUGUGGCUCCUUGGAAA 20 1010

CFTR-2789-75 - GUUGUGCUGUGGCUCCUUGGAAA 23 1011

CFTR-2789-76 - GGUUGUGCUGUGGCUCCUUGGAAA 24

1012

CFTR-2789-77 - GUUUAAAUGAUGACCAUUAG 20 1013

CFTR-2789-78 - GUACACACAUCAAAUGGUGUGAU 23 1014

CFTR-2789-79 - GGUACACACAUCAAAUGGUGUGAU 24 1015

Table 5B provides exemplary targeting domains for correcting a mutation (e.g., 2789+5G) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., 2789+5G), have a high level of orthogonality and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 5B

176

5535.1 CFTR-2789-95 - UUGUGCUGUGGCUCCUUGGAAA 22 1031

CFTR-2789-96 - UUAAAUGAUGACCAUUAG 18 1032

CFTR-2789-97 - UUUAAAUGAUGACCAUUAG 19 1033

CFTR-2789-98 - UGUUUAAAUGAUGACCAUUAG 21 1034

CFTR-2789-99 - UUGUUUAAAUGAUGACCAUUAG 22 1035

CFTR-2789-

- UUUGUUUAAAUGAUGACCAUUAG 23

100 1036

CFTR-2789-

- UUUUGUUUAAAUGAUGACCAUUAG 24

101 1037

CFTR-2789-

- UUUAGAUGUGGGCAUGGG 18

102 1038

CFTR-2789-

- AUUUAGAUGUGGGCAUGGG 19

103 1039

CFTR-2789-43 - AAUUUAGAUGUGGGCAUGGG 20 979

CFTR-2789-

- CACAUCAAAUGGUGUGAU 18

104 1040

CFTR-2789-

- ACACAUCAAAUGGUGUGAU 19

105 1041

CFTR-2789-

- CACACAUCAAAUGGUGUGAU 20

106 1042

CFTR-2789-

- ACA CACAUCAAAUGGUGUGAU 21

107 1043

CFTR-2789-

- UACACACAUCAAAUGGUGUGAU 22

108 1044

Table 5C provides exemplary targeting domains for correcting a mutation (e.g., 2789+5G) in the CFTR gene selected according to the third tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., 2789+5G), starts with a 5'G and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 5C

177

5535.1 110

CFTR-2789-

+ GCACAACCAAAGAAGCAGCCACC 23

111 1047

CFTR-2789-

- GAAUUUAGAUGUGGGCAUGGG 21

112 1048

CFTR-2789-

- GUGAAUUUAGAUGUGGGCAUGGG 23

113 1049

Table 5D provides exemplary targeting domains for correcting a mutation (e.g., 2789+5G) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., 2789+5G), and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 5D

178

5535.1 CFTR-2789-

+ UGGAGGAGCUAGGACUAC 18

123 1059

CFTR-2789-

+ UGUGGAGGAGCUAGGACUAC 20

67 1003

CFTR-2789-

+ ACAACCAAAG AAG CAGCCACC 21

124 1060

CFTR-2789-

+ CACAACCAAAG AAG CAGCCACC 22

125 1061

CFTR-2789-

+ AGCACAACCAAAGAAGCAGCCACC 24

126 1062

CFTR-2789-

+ AUCUUCCUUUGCUUUGUGUUC 21

127 1063

CFTR-2789-

+ CAUCUUCCUUUGCUUUGUGUUC 22

128 1064

CFTR-2789-

+ UCAUCUUCCUUUGCUUUGUGUUC 23

129 1065

CFTR-2789-

+ UUCAUCUUCCUUUGCUUUGUGUUC 24

130 1066

CFTR-2789-

- UGAAUUUAGAUGUGGGCAUGGG 22

131 1067

CFTR-2789-

- UGUGAAUUUAGAUGUGGGCAUGGG 24

132 1068

Table 5E provides exemplary targeting domains for correcting a mutation (e.g.,

2789+5G) in the CFTR gene selected according to the fifth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., 2789+5G), and PAM is NNGRRV. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 5E

179

5535.1 135

CFTR-2789-

+ AAUAAAACACAAUCUACACAA 21

136 1072

CFTR-2789-

+ AAAUAAAACACAAUCUACACAA 22

137 1073

CFTR-2789-

+ GAAAUAAAACACAAUCUACACAA 23

138 1074

CFTR-2789-

+ AGAAAUAAAACACAAUCUACACAA 24

139 1075

CFTR-2789-

+ AU U ACAAU AU U U AAU CAA 18

140 1076

CFTR-2789-

+ G AU U ACAAU AU U U AAU CAA 19

141 1077

CFTR-2789-

+ GGAUUACAAUAUUUAAUCAA 20

142 1078

CFTR-2789-

+ UGGAUUACAAUAUUUAAUCAA 21

143 1079

CFTR-2789-

+ GUGGAUUACAAUAUUUAAUCAA 22

144 1080

CFTR-2789-

+ AG UGG AU U ACAAU AU U U AAU CAA 23

145 1081

CFTR-2789-

+ UAGUGGAUUACAAUAUUUAAUCAA 24

146 1082

CFTR-2789-

+ CCAUAAUGCUUGGGAGAA 18

147 1083

CFTR-2789-

+ ACCAUAAUGCUUGGGAGAA 19

148 1084

CFTR-2789-

+ UACCAUAAUGCUUGGGAGAA 20

149 1085

CFTR-2789-

+ CUACCAUAAUGCUUGGGAGAA 21

150 1086

CFTR-2789-

+ ACUACCAUAAUGCUUGGGAGAA 22

151 1087

CFTR-2789-

+ CACU ACCAUAAUGCUUGGGAGAA 23

152 1088

CFTR-2789-

+ CCACUACCAUAAUGCUUGGGAGAA 24

153 1089

CFTR-2789-

+ AGAAGCAGCCACCUGGAA 18

154 1090

CFTR-2789-

+ AAGAAGCAGCCACCUGGAA 19

155 1091

CFTR-2789-

+ A A AG AAGCAGCCACCUGGAA 20

32 968

180

5535.1 CFTR-2789-

+ CAA AG AAG CAG CC ACC U G G AA 21

156 1092

CFTR-2789-

+ CCAAAGAAGCAGCCACCUGGAA 22

157 1093

CFTR-2789-

+ ACCAAAGAAGCAGCCACCUGGAA 23

158 1094

CFTR-2789-

+ AACCAAAGAAGCAGCCACCUGGAA 24

159 1095

CFTR-2789-

+ GGAGCCACAGCACAACCA 18

160 1096

CFTR-2789-

+ AG GAG CC ACAG CAC AACCA 19

161 1097

CFTR-2789-

+ AAG GAG CC ACAG CAC AACCA 20

162 1098

CFTR-2789-

+ CAAGGAGCCACAGCACAACCA 21

163 1099

CFTR-2789-

+ CCAAGGAGCCACAGCACAACCA 22

164 1100

CFTR-2789-

+ U CC A AG G AG C C A C AG C A C A AC C A 23

165 1101

CFTR-2789-

+ UUCCAAGGAGCCACAGCACAACCA 24

166 1102

CFTR-2789-

+ UGGAAUAUUCACUUUCCA 18

167 1103

CFTR-2789-

+ AUGGAAUAUUCACUUUCCA 19

168 1104

CFTR-2789-

+ CAUGGAAUAUUCACUUUCCA 20

65 1001

CFTR-2789-

+ ACAUGGAAUAUUCACUUUCCA 21

169 1105

CFTR-2789-

+ GACAUGGAAUAUUCACUUUCCA 22

170 1106

CFTR-2789-

+ GGACAUGGAAUAUUCACUUUCCA 23

171 1107

CFTR-2789-

+ AGGACAUGGAAUAUUCACUUUCCA 24

172 1108

CFTR-2789-

+ AAGAAGCAGCCACCUGGA 18

173 1109

CFTR-2789-

+ AAAGAAGCAGCCACCUGGA 19

174 1110

CFTR-2789-

+ CAAAGAAGCAGCCACCUGGA 20

175 1111

CFTR-2789- + CCAAAGAAGCAGCCACCUGGA 21 1112

181

5535.1 176

CFTR-2789-

+ ACCAAAGAAGCAGCCACCUGGA 22

177 1113

CFTR-2789-

+ A AC C A A AG AAGCAGCCACCUGGA 23

178 1114

CFTR-2789-

+ CAACCAAAGAAGCAGCCACCUGGA 24

179 1115

CFTR-2789-

+ GUGGAGGAGCUAGGACUA 18

180 1116

CFTR-2789-

+ UGUGGAGGAGCUAGGACUA 19

181 1117

CFTR-2789-

+ CUGUGGAGGAGCUAGGACUA 20

182 1118

CFTR-2789-

+ A ACC AAAG AAG CAG CCAC 18

183 1119

CFTR-2789-

+ CAACCAAAG AAG CAG CCAC 19

184 1120

CFTR-2789-

+ ACAACCAAAGAAGCAGCCAC 20

185 1121

CFTR-2789-

+ CACAACCAAAGAAGCAGCCAC 21

186 1122

CFTR-2789-

+ G CACAACCAAAG AAGCAG CCAC 22

187 1123

CFTR-2789-

+ AG CACAACCAAAG AAG CAG CCAC 23

188 1124

CFTR-2789-

+ CAG CACAACCAAAG AAG CAG CCAC 24

189 1125

CFTR-2789-

+ CAAUCUACACAAUAGGAC 18

190 1126

CFTR-2789-

+ ACAAUCUACACAAUAGGAC 19

191 1127

CFTR-2789-

+ CACAAUCUACACAAUAGGAC 20

192 1128

CFTR-2789-

+ ACACAAUCUACACAAUAGGAC 21

193 1129

CFTR-2789-

+ AACACAAUCUACACAAUAGGAC 22

194 1130

CFTR-2789-

+ AAACACAAUCUACACAAUAGGAC 23

195 1131

CFTR-2789-

+ AAAACACAAUCUACACAAUAGGAC 24

196 1132

CFTR-2789-

+ AUGGAAUAUUCACUUUCC 18

197 1133

182

5535.1 CFTR-2789-

+ CAUGGAAUAUUCACUUUCC 19

198 1134

CFTR-2789-

+ ACAUGGAAUAUUCACUUUCC 20

199 1135

CFTR-2789-

+ GACAUGGAAUAUUCACUUUCC 21

200 1136

CFTR-2789-

+ GGACAUGGAAUAUUCACUUUCC 22

201 1137

CFTR-2789-

+ AGGACAUGGAAUAUUCACUUUCC 23

202 1138

CFTR-2789-

+ UAGGACAUGGAAUAUUCACUUUCC 24

203 1139

CFTR-2789-

+ UUUCCACUACCAUAAUGC 18

204 1140

CFTR-2789-

+ CUUUCCACUACCAUAAUGC 19

205 1141

CFTR-2789-

+ UCUUUCCACUACCAUAAUGC 20

206 1142

CFTR-2789-

+ AUCUUUCCACUACCAUAAUGC 21

207 1143

CFTR-2789-

+ UAUCUUUCCACUACCAUAAUGC 22

208 1144

CFTR-2789-

+ UUAUCUUUCCACUACCAUAAUGC 23

209 1145

CFTR-2789-

+ CUUAUCUUUCCACUACCAUAAUGC 24

210 1146

CFTR-2789-

+ CACUACCAUAAUGCUUGG 18

211 1147

CFTR-2789-

+ CCACUACCAUAAUGCUUGG 19

212 1148

CFTR-2789-

+ UCCACUACCAUAAUGCUUGG 20

213 1149

CFTR-2789-

+ UUCCACUACCAUAAUGCUUGG 21

214 1150

CFTR-2789-

+ UUUCCACUACCAUAAUGCUUGG 22

215 1151

CFTR-2789-

+ CUUUCCACUACCAUAAUGCUUGG 23

216 1152

CFTR-2789-

+ UCUUUCCACUACCAUAAUGCUUGG 24

217 1153

CFTR-2789-

+ UUCCACUACCAUAAUGCU 18

218 1154

CFTR-2789- + UUUCCACUACCAUAAUGCU 19 1155

183

5535.1 219

CFTR-2789-

+ CUU UCCACUACCAUAAUGCU 20

48 984

CFTR-2789-

+ UCU UUCCACUACCAUAAUGCU 21

220 1156

CFTR-2789-

+ AUCUUUCCACUACCAUAAUGCU 22

221 1157

CFTR-2789-

+ UAUCUUUCCACUACCAUAAUGCU 23

222 1158

CFTR-2789-

+ U UAUCUUUCCACUACCAUAAUGCU 24

223 1159

CFTR-2789-

+ UCCACUACCAUAAUGCUU 18

224 1160

CFTR-2789-

+ U UCCACUACCAUAAUGCUU 19

225 1161

CFTR-2789-

+ U UUCCACUACCAUAAUGCUU 20

51 987

CFTR-2789-

+ CUU UCCACUACCAUAAUGCUU 21

226 1162

CFTR-2789-

+ UCU UUCCACUACCAUAAUGCUU 22

227 1163

CFTR-2789-

+ AUCUUUCCACUACCAUAAUGCUU 23

228 1164

CFTR-2789-

+ UAUCUUUCCACUACCAUAAUGCUU 24

229 1165

CFTR-2789-

- CCCAGGAACACAAAGCAA 18

230 1166

CFTR-2789-

- ACCCAG G A ACAC AAAG C AA 19

231 1167

CFTR-2789-8 - GACCCAGGAACACAAAGCAA 20 944

CFTR-2789-

- GGACCCAGGAACACAAAGCAA 21

232 1168

CFTR-2789-

- U G G ACCCAG GAACACAA AG C AA 22

233 1169

CFTR-2789-

- CUGGACCCAGGAACACAAAGCAA 23

234 1170

CFTR-2789-

- GCUGGACCCAGGAACACAAAGCAA 24

235 1171

CFTR-2789-

- ACCCAGGAACACAAAGCA 18

236 1172

CFTR-2789-

- GACCCAGGAACACAAAGCA 19

237 1173

CFTR-2789- - GGACCCAGGAACACAAAGCA 20 1174

184

5535.1 238

CFTR-2789-

- UGGACCCAGGAACACAAAGCA 21

239 1175

CFTR-2789-

- CUGGACCCAGGAACACAAAGCA 22

240 1176

CFTR-2789-

- GCUGGACCCAGGAACACAAAGCA 23

241 1177

CFTR-2789-

- UGCUGGACCCAGGAACACAAAGCA 24

242 1178

CFTR-2789-

- UGAAUUUAGAUGUGGGCA 18

243 1179

CFTR-2789-

- GUGAAUUUAGAUGUGGGCA 19

244 1180

CFTR-2789-

- UGUGAAUUUAGAUGUGGGCA 20

34 970

CFTR-2789-

- AUGUGAAUUUAGAUGUGGGCA 21

245 1181

CFTR-2789-

- GAUGUGAAUUUAGAUGUGGGCA 22

246 1182

CFTR-2789-

- UGAUGUGAAUUUAGAUGUGGGCA 23

247 1183

CFTR-2789-

- GUGAUGUGAAUUUAGAUGUGGGCA 24

248 1184

CFTR-2789-

- CUCCCAAGCAUUAUGGUA 18

249 1185

CFTR-2789-

- UCUCCCAAGCAUUAUGGUA 19

250 1186

CFTR-2789-

- UUCUCCCAAGCAUUAUGGUA 20

251 1187

CFTR-2789-

- UUUCUCCCAAGCAUUAUGGUA 21

252 1188

CFTR-2789-

- AUUUCUCCCAAGCAUUAUGGUA 22

253 1189

CFTR-2789-

- CAUUUCUCCCAAGCAUUAUGGUA 23

254 1190

CFTR-2789-

- UCAUUUCUCCCAAGCAUUAUGGUA 24

255 1191

CFTR-2789-

- UGGUUGUGCUGUGGCUCC 18

256 1192

CFTR-2789-

- UUGGUUGUGCUGUGGCUCC 19

257 1193

CFTR-2789-

- UUUGGUUGUGCUGUGGCUCC 20

258 1194

185

5535.1 CFTR-2789-

- CUUUGGUUGUGCUGUGGCUCC 21

259 1195

CFTR-2789-

- UCUUUGGUUGUGCUGUGGCUCC 22

260 1196

CFTR-2789-

- UUCUUUGGU UGUGCUGUGGCUCC 23

261 1197

CFTR-2789-

- CUUCUUUGGUUGUGCUGUGGCUCC 24

262 1198

CFTR-2789-

- GUGAAUUUAGAUGUGGGC 18

263 1199

CFTR-2789-

- UGUGAAUUUAGAUGUGGGC 19

264 1200

CFTR-2789-

- AUGUGAAUUUAGAUGUGGGC 20

265 1201

CFTR-2789-

- GAUGUGAAUUUAGAUGUGGGC 21

266 1202

CFTR-2789-

- UGAUGUGAAUUUAGAUGUGGGC 22

267 1203

CFTR-2789-

- GUGAUGUGAAUUUAGAUGUGGGC 23

268 1204

CFTR-2789-

- UGUGAUGUGAAUUUAGAUGUGGGC 24

269 1205

CFTR-2789-

- AACACAAAGCAAAGGAAG 18

270 1206

CFTR-2789-

- GAACACAAAGCAAAGGAAG 19

271 1207

CFTR-2789-

- GGAACACAAAGCAAAGGAAG 20

272 1208

CFTR-2789-

- AGGAACACAAAGCAAAGGAAG 21

273 1209

CFTR-2789-

- CAGGAACACAAAGCAAAGGAAG 22

274 1210

CFTR-2789-

- CCAGG AACACAAAGCAAAGGAAG 23

275 1211

CFTR-2789-

- CCCAGG AACACAAAGCAAAGGAAG 24

276 1212

CFTR-2789-

- UGGGCAUGGGAGGAAUAG 18

277 1213

CFTR-2789-

- GUGGGCAUGGGAGGAAUAG 19

278 1214

CFTR-2789-

- UGUGGGCAUGGGAGGAAUAG 20

279 1215

CFTR-2789- - AUGUGGGCAUGGGAGGAAUAG 21 1216

186

5535.1 280

CFTR-2789-

- GAUGUGGGCAUGGGAGGAAUAG 22

281 1217

CFTR-2789-

- AGAUGUGGGCAUGGGAGGAAUAG 23

282 1218

CFTR-2789-

- UAGAUGUGGGCAUGGGAGGAAUAG 24

283 1219

CFTR-2789-

- UCCCAAGCAUUAUGGUAG 18

284 1220

CFTR-2789-

- CUCCCAAGCAUUAUGGUAG 19

285 1221

CFTR-2789-

- UCUCCCAAGCAUUAUGGUAG 20

42 978

CFTR-2789-

- UUCUCCCAAGCAUUAUGGUAG 21

286 1222

CFTR-2789-

- UU UCUCCCAAGCAUUAUGGUAG 22

287 1223

CFTR-2789-

- AUUUCUCCCAAGCAUUAUGGUAG 23

288 1224

CFTR-2789-

- CAU UUCUCCCAAGCAUUAUGGUAG 24

289 1225

CFTR-2789-

- AUUUAGAUGUGGGCAUGG 18

290 1226

CFTR-2789-

- AAUUUAGAUGUGGGCAUGG 19

291 1227

CFTR-2789-

- GAAUUUAGAUGUGGGCAUGG 20

292 1228

CFTR-2789-

- UGAAUUUAGAUGUGGGCAUGG 21

293 1229

CFTR-2789-

- GUGAAUUUAGAUGUGGGCAUGG 22

294 1230

CFTR-2789-

- UGUGAAUUUAGAUGUGGGCAUGG 23

295 1231

CFTR-2789-

- AUGUGAAUUUAGAUGUGGGCAUGG 24

296 1232

CFTR-2789-

- AUGAUGACCAUUAGUUGG 18

297 1233

CFTR-2789-

- AAUGAUGACCAUUAGU UGG 19

298 1234

CFTR-2789-

- AAAUGAUGACCAUUAGUUGG 20

299 1235

CFTR-2789-

- UAAAUGAUGACCAUUAGUUGG 21

300 1236

187

5535.1 CFTR-2789-

- UUAAAUGAUGACCAUUAGUUGG 22

301 1237

CFTR-2789-

- UUUAAAUGAUGACCAUUAGUUGG 23

302 1238

CFTR-2789-

- GUUUAAAUGAUGACCAUUAGUUGG 24

303 1239

CFTR-2789-

- GAAUUUAGAUGUGGGCAU 18

304 1240

CFTR-2789-

- UGAAUUUAGAUGUGGGCAU 19

305 1241

CFTR-2789-

- GUGAAUUUAGAUGUGGGCAU 20

12 948

CFTR-2789-

- UGUGAAUUUAGAUGUGGGCAU 21

306 1242

CFTR-2789-

- AUGUGAAUUUAGAUGUGGGCAU 22

307 1243

CFTR-2789-

- GAUGUGAAUUUAGAUGUGGGCAU 23

308 1244

CFTR-2789-

- UGAUGUGAAUUUAGAUGUGGGCAU 24

309 1245

CFTR-2789-

- UGUGAUGUGAAUUUAGAU 18

310 1246

CFTR-2789-

- GUGUGAUGUGAAUUUAGAU 19

311 1247

CFTR-2789-

- GGUGUGAUGUGAAUUUAGAU 20

312 1248

CFTR-2789-

- UGGUGUGAUGUGAAUUUAGAU 21

313 1249

CFTR-2789-

- AUGGUGUGAUGUGAAUUUAGAU 22

314 1250

CFTR-2789-

- AAUGGUGUGAUGUGAAUUUAGAU 23

315 1251

CFTR-2789-

- AAAUGGUGUGAUGUGAAUUUAGAU 24

316 1252

CFTR-2789-

- GGUUGUGCUGUGGCUCCU 18

317 1253

CFTR-2789-

- UGGUUGUGCUGUGGCUCCU 19

318 1254

CFTR-2789-

- UUGGUUGUGCUGUGGCUCCU 20

47 983

CFTR-2789-

- UUUGGUUGUGCUGUGGCUCCU 21

319 1255

CFTR-2789- - CUUUGGUUGUGCUGUGGCUCCU 22 1256

188

5535.1 320

CFTR-2789-

- UCUUUGGUUGUGCUGUGGCUCCU 23

321 1257

CFTR-2789-

- UUCUUUGGUUGUGCUGUGGCUCCU 24

322 1258

CFTR-2789-

- AGGAAUAGGUGAAGAUGU 18

323 1259

CFTR-2789-

- GAGGAAUAGGUGAAGAUGU 19

324 1260

CFTR-2789-

- GGAGGAAUAGGUGAAGAUGU 20

325 1261

CFTR-2789-

- GGGAGGAAUAGGUGAAGAUGU 21

326 1262

CFTR-2789-

- UGGGAGGAAUAGGUGAAGAUGU 22

327 1263

CFTR-2789-

- AUGGGAGGAAUAGGUGAAGAUGU 23

328 1264

CFTR-2789-

- CAUGGGAGGAAUAGGUGAAGAUGU 24

329 1265

Table 6A provides exemplary targeting domains for correcting a mutation (e.g., 2789+5G) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., 2789+5G), have a high level of orthogonality and start with a 5'G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 6A

Table 6B provides exemplary targeting domains for correcting a mutation (e.g., 2789+5G) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., 2789+5G) and have a high level of

189

5535.1 orthogonality. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 6B

Table 6C provides exemplary targeting domains for correcting a mutation (e.g.,

2789+5G) in the CFTR gene selected according to the third tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., 2789+5G) and start with a 5'G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 6C

Table 6D provides exemplary targeting domains for correcting a mutation (e.g.,

2789+5G) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., 2789+5G). It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base

190

5535.1 pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 6D

Table 7A provides exemplary targeting domains for correcting a mutation (e.g., 3272- 26A->G) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., 3272-26A->G), have a high level of orthogonality and start with a 5'G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 7A

Table 7B provides exemplary targeting domains for correcting a mutation (e.g., 3272-

26A->G) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., 3272-26A->G) and have a high level of orthogonality. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

191

5535.1 Table 7B

Table 7C provides exemplary targeting domains for correcting a mutation (e.g., 3272- 6A->G) in the CFTR gene selected according to the third tier parameters. The targeting

192

5535.1 domains bind within 200 bp from a mutation (e.g., 3272-26A->G) and start with a 5'G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 7C

Table 7D provides exemplary targeting domains for correcting a mutation (e.g., 3272- 26A->G) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., 3272-26A->G). It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 7D

Table 8A provides exemplary targeting domains for correcting a mutation (e.g., 3272- 26A->G) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., 3272-26A->G), have a high level of orthogonality, start with a 5'G, and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of

193

5535.1 the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 8A

Table 8B provides exemplary targeting domains for correcting a mutation (e.g., 3272-

26A->G) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., 3272-26A->G), have a high level of orthogonality and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 8B

194

5535.1 CFTR-3272-69 + UUUUUUCACACUGGUGCCAUUCU 23 1350

CFTR-3272-70 + UUUUUUUCACACUGGUGCCAUUCU 24 1351

CFTR-3272-71 - ACAAAUCAUAUCUAUUCA 18 1352

CFTR-3272-72 - AACAAAUCAUAUCUAUUCA 19 1353

CFTR-3272-73 - UAACAAAUCAUAUCUAU UCA 20 1354

CFTR-3272-74 - AUAACAAAUCAUAUCUAUUCA 21 1355

CFTR-3272-75 - AAUAACAAAUCAUAUCUAUUCA 22 1356

CFTR-3272-76 - AAAUAACAAAUCAUAUCUAUUCA 23 1357

CFTR-3272-77 - AAAAUAACAAAUCAUAUCUAUUCA 24 1358

CFTR-3272-78 - UGGAAAUAUUUCACAGGC 18 1359

CFTR-3272-79 - AUGGAAAUAUUUCACAGGC 19 1360

CFTR-3272-33 - UAUGGAAAUAUUUCACAGGC 20 1314

CFTR-3272-80 - ACUGCGCUGGUUCCAAAU 18 1361

CFTR-3272-81 - CACUGCGCUGGUUCCAAAU 19 1362

CFTR-3272-82 - ACACUGCGCUGGUUCCAAAU 20 1363

CFTR-3272-83 - AACACUGCGCUGGUUCCAAAU 21 1364

CFTR-3272-84 - CAACACUGCGCUGGUUCCAAAU 22 1365

CFTR-3272-85 - UCAACACUGCGCUGGUUCCAAAU 23 1366

CFTR-3272-86 - ACUCUGUUCCACAAAGCU 18 1367

CFTR-3272-87 - AACUCUGUUCCACAAAGCU 19 1368

CFTR-3272-88 - AAACUCUGUUCCACAAAGCU 20 1369

Table 8C provides exemplary targeting domains for correcting a mutation (e.g., 3272- 26A->G) in the CFTR gene selected according to the third tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., 3272-26A->G), start with a 5'G and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 8C

195

5535.1 Table 8D provides exemplary targeting domains for correcting a mutation (e.g., 3272- 26A->G) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., 3272-26A->G), and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 8D

196

5535.1 107

CFTR-3272-

- CUCUGGUAGCCAAGU A A A A A A A 22

108 1389

CFTR-3272-

- UCUCUGGUAGCCAAGU A A A A A A A 23

109 1390

CFTR-3272-

- AUCUCUGGUAGCCAAGUAAAAAAA 24

110 1391

CFTR-3272-

- CUAUGGAAAUAUUUCACAGGC 21

111 1392

CFTR-3272-

- UCUAUGGAAAUAUUUCACAGGC 22

112 1393

CFTR-3272-

- UUCUAUGGAAAUAUUUCACAGGC 23

113 1394

CFTR-3272-

- UUUCUAUGGAAAUAUUUCACAGGC 24

114 1395

CFTR-3272-

- UGAAACUCUGUUCCACAAAGCU 22

115 1396

CFTR-3272-

- U UGAAACUC U G U U CC AC AAAG C U 23

116 1397

CFTR-3272-

- UUUGAAACUCUGUUCCACAAAGCU 24

117 1398

Table 8E provides exemplary targeting domains for correcting a mutation (e.g., 3272- 26A->G) in the CFTR gene selected according to the fifth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., 3272-26A->G), and PAM is NNGRRV. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 8E

197

5535.1 CFTR-3272-

+ UUGUAACAAGAUGAGUGAAAA 21

121 1402

CFTR-3272-

+ CUUGUAACAAGAUGAGUGAAAA 22

122 1403

CFTR-3272-

+ GCUUGUAACAAGAUGAGUGAAAA 23

123 1404

CFTR-3272-

+ AGCUUGUAACAAGAUGAGUGAAAA 24

124 1405

CFTR-3272-

+ GCCUGUGAAAUAUUUCCA 18

125 1406

CFTR-3272-

+ UGCCUGUGAAAUAUUUCCA 19

126 1407

CFTR-3272-

+ CUGCCUGUGAAAUAUUUCCA 20

127 1408

CFTR-3272-

+ CCUGCCUGUGAAAUAUUUCCA 21

128 1409

CFTR-3272-

+ UCCUGCCUGUGAAAUAUUUCCA 22

129 1410

CFTR-3272-

+ CUCCUGCCUGUGAAAUAUUUCCA 23

130 1411

CFTR-3272-

+ ACUCCUGCCUGUGAAAUAUUUCCA 24

131 1412

CFTR-3272-

+ UUACUUGGCUACCAGAGA 18

132 1413

CFTR-3272-

+ UUUACUUGGCUACCAGAGA 19

133 1414

CFTR-3272-

+ UUUUACUUGGCUACCAGAGA 20

25 1306

CFTR-3272-

+ UUUUUACUUGGCUACCAGAGA 21

134 1415

CFTR-3272-

+ UUUUUUACUUGGCUACCAGAGA 22

135 1416

CFTR-3272-

+ UUUUUUUACUUGGCUACCAGAGA 23

136 1417

CFTR-3272-

+ CUUUUUUUACUUGGCUACCAGAGA 24

137 1418

CFTR-3272-

+ AAGCUUGUAACAAGAUGA 18

138 1419

CFTR-3272-

+ UAAGCUUGUAACAAGAUGA 19

139 1420

CFTR-3272-

+ UUAAGCUUGUAACAAGAUGA 20

140 1421

CFTR-3272- + UUUAAGCUUGUAACAAGAUGA 21 1422

198

5535.1 141

CFTR-3272-

+ UUUUAAGCUUGUAACAAGAUGA 22

142 1423

CFTR-3272-

+ CUUUUAAGCUUGUAACAAGAUGA 23

143 1424

CFTR-3272-

+ CCUUUUAAGCUUGUAACAAGAUGA 24

144 1425

CFTR-3272-

+ CUUUUUUUACUUGGCUAC 18

145 1426

CFTR-3272-

+ UCUUUUUUUACUUGGCUAC 19

146 1427

CFTR-3272-

+ CUCUUUUUUUACUUGGCUAC 20

147 1428

CFTR-3272-

+ CCUCUUUUUUUACUUGGCUAC 21

148 1429

CFTR-3272-

+ CCCUCUUUUUUUACUUGGCUAC 22

149 1430

CFTR-3272-

+ ACCCUCUUUUUUUACUUGGCUAC 23

150 1431

CFTR-3272-

+ UACCCUCUUUUUUUACUUGGCUAC 24

151 1432

CFTR-3272-

+ CGCAGUGUUGACAGGUAC 18

152 1433

CFTR-3272-

+ GCGCAGUGUUGACAGGUAC 19

153 1434

CFTR-3272-

+ AGCGCAGUGUUGACAGGUAC 20

154 1435

CFTR-3272-

+ CAGCGCAGUGUUGACAGGUAC 21

155 1436

CFTR-3272-

+ CCAGCGCAGUGUUGACAGGUAC 22

156 1437

CFTR-3272-

+ ACCAGCGCAGUGUUGACAGGUAC 23

157 1438

CFTR-3272-

+ AACCAGCGCAGUGUUGACAGGUAC 24

158 1439

CFTR-3272-

+ UUUCAUAAUAUCUUGUAC 18

159 1440

CFTR-3272-

+ AUUUCAUAAUAUCUUGUAC 19

160 1441

CFTR-3272-

+ AAUUUCAUAAUAUCUUGUAC 20

161 1442

CFTR-3272-

+ UAAUUUCAUAAUAUCUUGUAC 21

162 1443

199

5535.1 CFTR-3272-

+ GUAAUUUCAUAAUAUCUUGUAC 22

163 1444

CFTR-3272-

+ UGUAAUUUCAUAAUAUCUUGUAC 23

164 1445

CFTR-3272-

+ AUGUAAUUUCAUAAUAUCUUGUAC 24

165 1446

CFTR-3272-

+ AGGCUGCCGUCCGAAGGC 18

166 1447

CFTR-3272-

+ AAGGCUGCCGUCCGAAGGC 19

167 1448

CFTR-3272-

+ UAAGGCUGCCGUCCGAAGGC 20

168 1449

CFTR-3272-

+ GU AAGGCUGCCGUCCGAAGGC 21

169 1450

CFTR-3272-

+ AGUAAGGCUGCCGUCCGAAGGC 22

170 1451

CFTR-3272-

+ AAGUAAGGCUGCCGUCCGAAGGC 23

171 1452

CFTR-3272-

+ AAAGUAAGGCUGCCGUCCGAAGGC 24

172 1453

CFTR-3272-

+ UUUACUUGGCUACCAGAG 18

173 1454

CFTR-3272-

+ UUUUACUUGGCUACCAGAG 19

174 1455

CFTR-3272-

+ UUUUUACUUGGCUACCAGAG 20

175 1456

CFTR-3272-

+ UUUUUUACUUGGCUACCAGAG 21

176 1457

CFTR-3272-

+ UUUUUUUACUUGGCUACCAGAG 22

177 1458

CFTR-3272-

+ CUUUUUUUACUUGGCUACCAGAG 23

178 1459

CFTR-3272-

+ UCUUUUUUUACUUGGCUACCAGAG 24

179 1460

CFTR-3272-

+ UGUAAAUUCAGAGCUUUG 18

180 1461

CFTR-3272-

+ AUGUAAAUUCAGAGCUUUG 19

181 1462

CFTR-3272-

+ UAUGUAAAUUCAGAGCUUUG 20

35 1316

CFTR-3272-

+ GUAUGUAAAUUCAGAGCUUUG 21

182 1463

CFTR-3272- + AGUAUGUAAAUUCAGAGCUUUG 22 1464

200

5535.1 183

CFTR-3272-

+ CAGUAUGUAAAUUCAGAGCUUUG 23

184 1465

CFTR-3272-

+ GCAGUAUGUAAAUUCAGAGCUUUG 24

185 1466

CFTR-3272-

+ UACUUGGCUACCAGAGAU 18

186 1467

CFTR-3272-

+ UUACUUGGCUACCAGAGAU 19

187 1468

CFTR-3272-

+ UUUACUUGGCUACCAGAGAU 20

37 1318

CFTR-3272-

+ UUUUACUUGGCUACCAGAGAU 21

188 1469

CFTR-3272-

+ UUUUUACUUGGCUACCAGAGAU 22

189 1470

CFTR-3272-

+ UUUUUUACUUGGCUACCAGAGAU 23

190 1471

CFTR-3272-

+ UUUUUUUACUUGGCUACCAGAGAU 24

191 1472

CFTR-3272-

+ AAAAUUGGACUCCUGCCU 18

192 1473

CFTR-3272-

+ GAAAAUUGGACUCCUGCCU 19

193 1474

CFTR-3272-

+ UGAAAAUUGGACUCCUGCCU 20

194 1475

CFTR-3272-

+ GUGAAAAUUGGACUCCUGCCU 21

195 1476

CFTR-3272-

+ AGUGAAAAUUGGACUCCUGCCU 22

196 1477

CFTR-3272-

+ GAGUGAAAAUUGGACUCCUGCCU 23

197 1478

CFTR-3272-

+ UGAGUGAAAAUUGGACUCCUGCCU 24

198 1479

CFTR-3272-

+ UCAAAGUAAGGCUGCCGU 18

199 1480

CFTR-3272-

+ UUCAAAGUAAGGCUGCCGU 19

200 1481

CFTR-3272-

+ UUUCAAAGUAAGGCUGCCGU 20

201 1482

CFTR-3272-

+ GUUUCAAAGUAAGGCUGCCGU 21

202 1483

CFTR-3272-

+ AGUUUCAAAGUAAGGCUGCCGU 22

203 1484

201

5535.1 CFTR-3272-

+ GAGUUUCAAAGUAAGGCUGCCGU 23

204 1485

CFTR-3272-

+ AGAGUUUCAAAGUAAGGCUGCCGU 24

205 1486

CFTR-3272-

+ GUUGGCAGUAUGUAAAUU 18

206 1487

CFTR-3272-

+ AGUUGGCAGUAUGUAAAUU 19

207 1488

CFTR-3272-

+ CAGU UGGCAGUAUGUAAAUU 20

208 1489

CFTR-3272-

+ CCAGU UGGCAGUAUGUAAAUU 21

209 1490

CFTR-3272-

+ ACCAGUUGGCAGUAUGUAAAUU 22

210 1491

CFTR-3272-

+ AACCAGUUGGCAGUAUGUAAAUU 23

211 1492

CFTR-3272-

+ G AACCAG U UGG CAG U AUG U AAAU U 24

212 1493

CFTR-3272-

+ AUGUAAAUUCAGAGCUUU 18

213 1494

CFTR-3272-

+ UAUGUAAAUUCAGAGCUUU 19

214 1495

CFTR-3272-

+ GUAUGUAAAUUCAGAGCUUU 20

215 1496

CFTR-3272-

+ AGUAUGUAAAUUCAGAGCUUU 21

216 1497

CFTR-3272-

+ CAGUAUGUAAAUUCAGAGCUUU 22

217 1498

CFTR-3272-

+ GCAGUAUGUAAAUUCAGAGCUUU 23

218 1499

CFTR-3272-

+ GGCAGUAUGUAAAUUCAGAGCUUU 24

219 1500

CFTR-3272-

- CUGGUAGC C A AG U A A A A A 18

220 1501

CFTR-3272-

- UCUGGUAGCCAAGU A A A A A 19

221 1502

CFTR-3272-

- CUCUGGUAGCCAAGU A A A A A 20

222 1503

CFTR-3272-

- UCUCUGGUAGCCAAGUAAAAA 21

223 1504

CFTR-3272-

- AUCUCUGGUAGCCAAGUAAAAA 22

224 1505

CFTR-3272- - CAUCUCUGGUAGCCAAGU A A A A A 23 1506

202

5535.1 225

CFTR-3272-

- CCAUCUCUGGUAGCCAAGUAAAAA 24

226 1507

CFTR-3272-

- ACACUGCGCUGGUUCCAA 18

227 1508

CFTR-3272-

- AACACUGCGCUGGUUCCAA 19

228 1509

CFTR-3272-

- CAACACUGCGCUGGUUCCAA 20

229 1510

CFTR-3272-

- UCAACACUGCGCUGGUUCCAA 21

230 1511

CFTR-3272-

- GUCAACACUGCGCUGGU UCCAA 22

231 1512

CFTR-3272-

- UGUCAACACUGCGCUGGUUCCAA 23

232 1513

CFTR-3272-

- CUGUCAACACUGCGCUGGUUCCAA 24

233 1514

CFTR-3272-

- GCUGGU UCCAAAUGAGAA 18

234 1515

CFTR-3272-

- CGCUGGU UCCAAAUGAGAA 19

235 1516

CFTR-3272-

- GCGCUGGU UCCAAAUGAGAA 20

236 1517

CFTR-3272-

- UGCGCUGGUUCCAAAUGAGAA 21

237 1518

CFTR-3272-

- CUGCGCUGGUUCCAAAUGAGAA 22

238 1519

CFTR-3272-

- ACUGCGCUGGUUCCAAAUGAGAA 23

239 1520

CFTR-3272-

- CACUGCGCUGGUUCCAAAUGAGAA 24

240 1521

CFTR-3272-

- AUCUUGUUACAAGCUUAA 18

241 1522

CFTR-3272-

- CAUCUUGUUACAAGCUUAA 19

242 1523

CFTR-3272-

- UCAUCUUGUUACAAGCUUAA 20

243 1524

CFTR-3272-

- CUCAUCUUGUUACAAGCUUAA 21

244 1525

CFTR-3272-

- ACUCAUCUUGUUACAAGCUUAA 22

245 1526

CFTR-3272-

- CACUCAUCUUGUUACAAGCUUAA 23

246 1527

203

5535.1 CFTR-3272-

- UCACUCAUCUUGUUACAAGCUUAA 24

247 1528

CFTR-3272-

- UAUUUGCAGUGUUUUCUA 18

248 1529

CFTR-3272-

- UUAUUUGCAGUGUUUUCUA 19

249 1530

CFTR-3272-

- GUUAUUUGCAGUGUUUUCUA 20

42 1323

CFTR-3272-

- UGUUAUUUGCAGUGUUUUCUA 21

250 1531

CFTR-3272-

- AUGUUAUUUGCAGUGU UUUCUA 22

251 1532

CFTR-3272-

- UAUGUUAUUUGCAGUGUUUUCUA 23

252 1533

CFTR-3272-

- UUAUGUUAUUUGCAGUGUUUUCUA 24

253 1534

CFTR-3272-

- AUGGAAAUAUUUCACAGG 18

254 1535

CFTR-3272-

- UAUGGAAAUAUUUCACAGG 19

255 1536

CFTR-3272-

- CUAUGGAAAUAUUUCACAGG 20

256 1537

CFTR-3272-

- UCUAUGGAAAUAUUUCACAGG 21

257 1538

CFTR-3272-

- UUCUAUGGAAAUAUUUCACAGG 22

258 1539

CFTR-3272-

- UU UCUAUGGAAAUAUU UCACAGG 23

259 1540

CFTR-3272-

- UU UUCUAUGGAAAUAU UUCACAGG 24

260 1541

CFTR-3272-

- UACAAGCUUAAAAGGACU 18

261 1542

CFTR-3272-

- UUACAAGCUUAAAAGGACU 19

262 1543

CFTR-3272-

- GU UACAAGCUUAAAAGGACU 20

263 1544

CFTR-3272-

- UGUUACAAGCUUAAAAGGACU 21

264 1545

CFTR-3272-

- U UG U UACAAGCU U AAAAGG ACU 22

265 1546

CFTR-3272-

- CUUGUUACAAGCUUAAAAGGACU 23

266 1547

CFTR-3272- - UCUUGUUACAAGCUUAAAAGGACU 24 1548

204

5535.1 267

CFTR-3272-

- UCGGACGGCAGCCU UACU 18

268 1549

CFTR-3272-

- UUCGGACGGCAGCCUUACU 19

269 1550

CFTR-3272-

- CUUCGGACGGCAGCCUUACU 20

270 1551

CFTR-3272-

- CCUUCGGACGGCAGCCU UACU 21

271 1552

CFTR-3272-

- GCCUUCGGACGGCAGCCUUACU 22

272 1553

CFTR-3272-

- UGCCUUCGGACGGCAGCCUUACU 23

273 1554

CFTR-3272-

- GUGCCU UCGGACGGCAGCCUUACU 24

274 1555

CFTR-3272-

- UAUGGACACUUCGUGCCU 18

275 1556

CFTR-3272-

- CUAUGGACACUUCGUGCCU 19

276 1557

CFTR-3272-

- ACUAUGGACACUUCGUGCCU 20

277 1558

CFTR-3272-

- GACUAUGGACACUUCGUGCCU 21

278 1559

CFTR-3272-

- GGACUAUGGACACUUCGUGCCU 22

279 1560

CFTR-3272-

- AGGACUAUGGACACUUCGUGCCU 23

280 1561

CFTR-3272-

- AAGGACUAUGGACACUUCGUGCCU 24

281 1562

CFTR-3272-

- UUAUUUGCAGUGU UUUCU 18

282 1563

CFTR-3272-

- GU UAUUUGCAGUGUUU UCU 19

283 1564

CFTR-3272-

- UGUUAUUUGCAGUGUU UUCU 20

284 1565

CFTR-3272-

- AUGUUAUUUGCAGUGUUUUCU 21

285 1566

CFTR-3272-

- UAUGUUAUUUGCAGUGUUUUCU 22

286 1567

CFTR-3272-

- UUAUGUUAUUUGCAGUGUUUUCU 23

287 1568

CFTR-3272-

- UU UAUGUUAUUUGCAGUGUUUUCU 24

288 1569

205

5535.1 CFTR-3272-

- U C A A AG A A U G G C AC C AG U 18

289 1570

CFTR-3272-

- UUCAAAGAAUGGCACCAGU 19

290 1571

CFTR-3272-

- AUUCAAAGAAUGGCACCAGU 20

291 1572

CFTR-3272-

- UAUUCAAAGAAUGGCACCAGU 21

292 1573

CFTR-3272-

- CUAUUCAAAGAAUGGCACCAGU 22

293 1574

CFTR-3272-

- U C U A U U C A A AG A A UGGCACCAGU 23

294 1575

CFTR-3272-

- AUCUAUUCAAAGAAUGGCACCAGU 24

295 1576

CFTR-3272-

- UUUCAGGUACAAGAUAUU 18

296 1577

CFTR-3272-

- UUUUCAGGUACAAGAUAUU 19

297 1578

CFTR-3272-

- UUUUUCAGGUACAAGAUAUU 20

298 1579

CFTR-3272-

- CUUUUUCAGGUACAAGAUAUU 21

299 1580

CFTR-3272-

- UCUUUUUCAGGUACAAGAUAUU 22

300 1581

CFTR-3272-

- GUCUUUUUCAGGUACAAGAUAUU 23

301 1582

CFTR-3272-

- AGUCUUUUUCAGGUACAAGAUAUU 24

302 1583

Table 9A provides exemplary targeting domains for correcting a mutation (e.g., 3272- 26A->G) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., 3272-26A->G) and have a high level of orthogonality. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 9A

206

5535.1 Length

CFTR-3272-303 - AUGGCACCAGUGUGAAA 17 1584

CFTR-3272-304 + UGCCAUUCUUUGAAUAG 17 1585

CFTR-3272-305 + UUGGCAGUAUGUAAAUU 17 1586

CFTR-3272-306 + AAGUGUCCAUAGUCCUU 17 1587

CFTR-3272-307 - AGAAUGGCACCAGUGUGAAA 20 1588

CFTR-3272-308 + UGGUGCCAUUCUUUGAAUAG 20 1589

CFTR-3272-309 + ACGAAGUGUCCAUAGUCCUU 20 1590

Table 9B provides exemplary targeting domains for correcting a mutation (e.g., 3272- 26A->G) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., 3272-26A->G). It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 9B

Table 10A provides exemplary targeting domains for correcting a mutation (e.g., deltaF508) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., deltaF508), have a high level of orthogonality and start with a 5'G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 10A

207

5535.1 1st Tier

Target Site

gRNA Name DNA Strand Targeting Domain

Length Seq ID

CFTR-

- GGGUAAGCUACUGUGAA 17

DeltaF508-l 402

CFTR-

- GAACUGGAGCCUUCAGA 17

DeltaF508-2 401

CFTR-

+ GACUAACCGAUUGAAUA 17

DeltaF508-3 403

CFTR-

- GGUGAUUAUGGGAGAAC 17

DeltaF508-4 400

CFTR-

+ GGUGCCAGGCAUAAUCC 17

DeltaF508-5 394

CFTR-

- G G U A A A A U U A AG C AC AG 17

DeltaF508-6 390

CFTR-

+ GUAUCUAUAUUCAUCAU 17

DeltaF508-7 392

CFTR-

+ GAGCCAAAUAUAUAAUU 17

DeltaF508-8 404

CFTR-

- GGAGAACUGGAGCCUUCAGA 20

DeltaF508-9 397

CFTR-

+ GUAGACUAACCGAUUGAAUA 20

DeltaF508-10 398

CFTR-

+ GUCAUUAUCAAAUCACGCUC 20

DeltaF508-ll 399

CFTR-

- G AG G G U A A A A U U A AG C AC AG 20

DeltaF508-12 387

CFTR-

- GGGAGAACUGGAGCCUUCAG 20

DeltaF508-13 396

CFTR-

- GAUAAUGACCUAAUAAUGAU 20

DeltaF508-14 395

Table 10B provides exemplary targeting domains for correcting a mutation (e.g., deltaF508) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., deltaF508) and have a high level of orthogonality. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 10B

208

5535.1 2nd Tier

Target Site

gRNA Name DNA Strand Targeting Domain

Length Seq ID

CFTR-

+ AAUUUGGGUAGUGUGAA 17

DeltaF508-15 449

CFTR-

- CCAGACUUCACUUCUAA 17

DeltaF508-16 438

CFTR-

- UAAUGACCUAAUAAUGA 17

DeltaF508-17 436

CFTR-

+ UUAAUUUUACCCUCUGA 17

DeltaF508-18 418

CFTR-

+ UAAUUUGGGUAGUGUGA 17

DeltaF508-19 448

CFTR-

- UUUUCCUGGAUUAUGCC 17

DeltaF508-20 414

CFTR-

+ UUUUCUUUAAUGGUGCC 17

DeltaF508-21 417

CFTR-

- UCUGUUCUCAGUUUUCC 17

DeltaF508-22 413

CFTR-

+ AUUAUCAAAUCACGCUC 17

DeltaF508-23 452

CFTR-

+ CCAUUAGAAGUGAAGUC 17

DeltaF508-24 450

CFTR-

- AGCAUGCCAACUAGAAG 17

DeltaF508-25 391

CFTR-

- AGAACUGGAGCCUUCAG 17

DeltaF508-26 441

CFTR-

+ CAGUAGCUUACCCAUAG 17

DeltaF508-27 446

CFTR-

- UUGGCUCCAUAUUCAAU 17

DeltaF508-28 443

CFTR-

- CUUCUAAUGGUGAUUAU 17

DeltaF508-29 440

CFTR-

+ UUCUUACCUCUUCUAGU 17

DeltaF508-30 416

CFTR-

- UACCCAAAUUAUAUAUU 17

DeltaF508-31 442

CFTR-

- UAUGGGUAAGCUACUGUGAA 20

DeltaF508-32 428

CFTR-

+ UAUAAUUUGGGUAGUGUGAA 20

DeltaF508-33 433

CFTR-

- UUUCCAGACUUCACUUCUAA 20

DeltaF508-34 420

209

5535.1 CFTR-

+ ACCAAUGAUAUUUUCU UUAA 20

DeltaF508-35 1597

CFTR-

- UGAUAAUGACCUAAUAAUGA 20

DeltaF508-36 419

CFTR-

+ UGCU UAAUUUUACCCUCUGA 20

DeltaF508-37 412

CFTR-

+ AUAUAAUUUGGGUAGUGUGA 20

DeltaF508-38 432

CFTR-

- UUCACUUCUAAUGGUGAUUA 20

DeltaF508-39 421

CFTR-

- AAUGGUGAUUAUGGGAGAAC 20

DeltaF508-40 423

CFTR-

- CAGU UUUCCUGGAUUAUGCC 20

DeltaF508-41 406

CFTR-

+ AUAUUUUCUUUAAUGGUGCC 20

DeltaF508-42 411

CFTR-

+ AAUGGUGCCAGGCAUAAUCC 20

DeltaF508-43 389

CFTR-

- CAU UCUGUUCUCAGUU UUCC 20

DeltaF508-44 405

CFTR-

+ UCACCAUUAGAAGUGAAGUC 20

DeltaF508-45 434

CFTR-

- C A A AG C A U G C C A AC U AG A AG 20

DeltaF508-46 408

CFTR-

+ UCACAGUAGCUUACCCAUAG 20

DeltaF508-47 429

CFTR-

- UAUUUGGCUCCAUAUUCAAU 20

DeltaF508-48 425

CFTR-

+ UCUGUAUCUAUAUUCAUCAU 20

DeltaF508-49 409

CFTR-

- ACCAUUAAAGAAAAUAUCAU 20

DeltaF508-50 1598

CFTR-

- UCACUUCUAAUGGUGAUUAU 20

DeltaF508-51 422

CFTR-

+ AGUUUCUUACCUCUUCUAGU 20

DeltaF508-52 388

CFTR-

+ AUGGAGCCAAAUAUAUAAUU 20

DeltaF508-53 430

CFTR-

- CACUACCCAAAUUAUAUAUU 20

DeltaF508-54 424

210

5535.1 Table IOC provides exemplary targeting domains for correcting a mutation (e.g., deltaF508) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., deltaF508). It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table IOC

Table 11A provides exemplary targeting domains for correcting a mutation (e.g. deltaF508) in the CFTR gene selected according to the first tier parameters. The targetin domains bind within 200 bp from a mutation (e.g., deltaF508), have a high level of

211

5535.1 orthogonality, start with a 5'G, and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 11A

Table 11B provides exemplary targeting domains for correcting a mutation (e.g., deltaF508) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., deltaF508), have a high level of orthogonality and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting

212

5535.1 domains in the Table can be used with a S. aureus Cas9 molecule that generates stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 11B

213

5535.1 CFTR-

+ AUGGAGCCAAAUAUAUAAU 19

DeltaF508-97 1626

CFTR-

+ UAUGGAGCCAAAUAUAUAAU 20

DeltaF508-98 689

CFTR-

+ AUAUGGAGCCAAAUAUAUAAU 21

DeltaF508-99 1627

CFTR- DeltaF508- + AAUAUGGAGCCAAAUAUAUAAU 22

100 1628

CFTR- DeltaF508- + UGAAUAUGGAGCCAAAUAUAUAAU 24

101 1629

CFTR- DeltaF508- + UCAUUAUCAAAUCACGCU 18

102 1630

CFTR- DeltaF508- + AGGUCAUUAUCAAAUCACGCU 21

103 1631

CFTR- DeltaF508- + UAGGUCAUUAUCAAAUCACGCU 22

104 1632

CFTR- DeltaF508- + UUAGGUCAUUAUCAAAUCACGCU 23

105 1633

CFTR- DeltaF508- + AUUAGGUCAUUAUCAAAUCACGCU 24

106 1634

CFTR- DeltaF508- - UGGGAGAACUGGAGCCUUCA 20

107 661

CFTR- DeltaF508- - AUGGGUAAGCUACUGUGA 18

108 1635

CFTR- DeltaF508- - UAUGGGUAAGCUACUGUGA 19

109 1636

CFTR- DeltaF508- - CUAUGGGUAAGCUACUGUGA 20

110 675

CFTR- DeltaF508- - UCUAUGGGUAAGCUACUGUGA 21

111 1637

214

5535.1 CFTR- DeltaF508- - CUCUAUGGGUAAGCUACUGUGA 22

112 1638

CFTR- DeltaF508- - CCUCUAUGGGUAAGCUACUGUGA 23

113 1639

CFTR- DeltaF508- - UCCUCUAUGGGUAAGCUACUGUGA 24

114 1640

CFTR- DeltaF508- - AUUCUGUUCUCAGUUUUC 18

115 1641

CFTR- DeltaF508- - CAUUCUGUUCUCAGUUUUC 19

116 1642

CFTR- DeltaF508- - UCAUUCUGUUCUCAGUUUUC 20

117 664

CFTR- DeltaF508- - UUCAUUCUGUUCUCAGUUUUC 21

118 1643

CFTR- DeltaF508- - UUUCAUUCUGUUCUCAGUUUUC 22

119 1644

CFTR- DeltaF508- - AUUUCAUUCUGUUCUCAGUUUUC 23

120 1645

CFTR- DeltaF508- - AAUUUCAUUCUGUUCUCAGUUUUC 24

121 1646

CFTR- DeltaF508- - U A A A A UUAAGCACAGUGG 18

122 1647

CFTR- DeltaF508- - AGGGUAAAAUUAAGCACAGUGG 22

123 1648

CFTR- DeltaF508- - AGAGGGUAAAAUUAAGCACAGUGG 24

124 1649

CFTR- DeltaF508- - UGAUAAUGACCUAAUAAUG 19

125 1650

215

5535.1 CFTR- DeltaF508- - UUGAUAAUGACCUAAUAAUG 20

126 656

CFTR- DeltaF508- - UUUGAUAAUGACCUAAUAAUG 21

127 1651

CFTR- DeltaF508- - AUUUGAUAAUGACCUAAUAAUG 22

128 1652

CFTR- DeltaF508- - UGAUUUGAUAAUGACCUAAUAAUG 24

129 1653

CFTR- DeltaF508- - UCAUUGGUGUUUCCUAUG 18

130 1654

CFTR- DeltaF508- - AUCAUUGGUGUUUCCUAUG 19

131 1655

CFTR- DeltaF508- - UAUCAUUGGUGUUUCCUAUG 20

132 1656

CFTR- DeltaF508- - AUAUCAUUGGUGUUUCCUAUG 21

133 1657

CFTR- DeltaF508- - AAUAUCAUUGGUGUUUCCUAUG 22

134 1658

CFTR- DeltaF508- - AAAUAUCAUUGGUGUUUCCUAUG 23

135 1659

CFTR- DeltaF508- - AAAAUAUCAUUGGUGUUUCCUAUG 24

136 1660

CFTR- DeltaF508- - CUCUAUGGGUAAGCUACU 18

137 1661

CFTR- DeltaF508- - CCUCUAUGGGUAAGCUACU 19

138 1662

CFTR- DeltaF508- - UCCUCUAUGGGUAAGCUACU 20

139 674

216

5535.1 CFTR- DeltaF508- - UUCCUCUAUGGGUAAGCUACU 21

140 1663

CFTR- DeltaF508- - UUUCCUCUAUGGGUAAGCUACU 22

141 1664

CFTR- DeltaF508- - UGUUUCCUCUAUGGGUAAGCUACU 24

142 1665

CFTR- DeltaF508- - UAUAUUUAUGUUUCCUCU 18

143 1666

CFTR- DeltaF508- - AUAUAUUUAUGUUUCCUCU 19

144 1667

CFTR- DeltaF508- - CAUAUAUUUAUGUUUCCUCU 20

145 673

CFTR- DeltaF508- - ACAUAUAUUUAUGUUUCCUCU 21

146 1668

CFTR- DeltaF508- - UACAUAUAUUUAUGUUUCCUCU 22

147 1669

CFTR- DeltaF508- - CUACAUAUAUUUAUGUUUCCUCU 23

148 1670

CFTR- DeltaF508- - UCUACAUAUAUUUAUGUUUCCUCU 24

149 1671

Table 11C provides exemplary targeting domains for correcting a mutation (e.g., deltaF508) in the CFTR gene selected according to the third tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., deltaF508), start with a 5'G and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 11C

3rd Tier

217

5535.1 Target Site gRNA Name DNA Strand Targeting Domain

Length Seq ID

CFTR-

+ GCAUAAUCCAGGAAAACUGAGAA 23

DeltaF508-150 1672

CFTR-

+ GGCAUAAUCCAGGAAAACUGAGAA 24

DeltaF508-151 1673

Table 11D provides exemplary targeting domains for correcting a mutation (e.g., deltaF508) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., deltaF508), and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 11D

Table HE provides exemplary targeting domains for correcting a mutation (e.g., deltaF508) in the CFTR gene selected according to the fifth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., deltaF508), and PAM is NNGRRV. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with

218

5535.1 a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table HE

219

5535.1 CFTR- DeltaF508- + UUCUCCCAUAAUCACCAUUAGAA 23

170 1690

CFTR- DeltaF508- + GUUCUCCCAUAAUCACCAUUAGAA 24

171 1691

CFTR- DeltaF508- + UUCACAGUAGCUUACCCA 18

172 1692

CFTR- DeltaF508- + AUUCACAGUAGCUUACCCA 19

173 1693

CFTR- DeltaF508- + CAUUCACAGUAGCUUACCCA 20

174 693

CFTR- DeltaF508- + CCAUUCACAGUAGCUUACCCA 21

175 1694

CFTR- DeltaF508- + UCCAUUCACAGUAGCUUACCCA 22

176 1695

CFTR- DeltaF508- + AUCCAUUCACAGUAGCUUACCCA 23

177 1696

CFTR- DeltaF508- + GAUCCAUUCACAGUAGCUUACCCA 24

178 1697

CFTR- DeltaF508- + CUGUAUCUAUAUUCAUCA 18

179 1698

CFTR- DeltaF508- + UCUGUAUCUAUAUUCAUCA 19

180 1699

CFTR- DeltaF508- + UUCUGUAUCUAUAUUCAUCA 20

181 686

CFTR- DeltaF508- + CUUCUGUAUCUAUAUUCAUCA 21

182 1700

CFTR- DeltaF508- + GCUUCUGUAUCUAUAUUCAUCA 22

183 1701

220

5535.1 CFTR- DeltaF508- + CGCUUCUGUAUCUAUAUUCAUCA 23

184 1702

CFTR- DeltaF508- + ACGCUUCUGUAUCUAUAUUCAUCA 24

185 1703

CFTR- DeltaF508- + AGGAAAACUGAGAACAGA 18

186 1704

CFTR- DeltaF508- + CAGGAAAACUGAGAACAGA 19

187 1705

CFTR- DeltaF508- + CCAGGAAAACUGAGAACAGA 20

188 681

CFTR- DeltaF508- + UCCAGGAAAACUGAGAACAGA 21

189 1706

CFTR- DeltaF508- + AUCCAGGAAAACUGAGAACAGA 22

190 1707

CFTR- DeltaF508- + AAUCCAGGAAAACUGAGAACAGA 23

191 1708

CFTR- DeltaF508- + UAAUCCAGGAAAACUGAGAACAGA 24

192 1709

CFTR- DeltaF508- + AGACUAACCGAUUGAAUA 18

193 1710

CFTR- DeltaF508- + UAGACUAACCGAUUGAAUA 19

194 1711

CFTR-

+ GU AGACUAACCGAUUGAAUA 20

DeltaF508-10 398

CFTR- DeltaF508- + UGUAGACUAACCGAUUGAAUA 21

195 1712

CFTR- DeltaF508- + AUGUAGACUAACCGAUUGAAUA 22

196 1713

CFTR-

+ UAUGUAGACUAACCGAUUGAAUA 23

DeltaF508- 1714

221

5535.1 197

CFTR- DeltaF508- + AUAUGUAGACUAACCGAUUGAAUA 24

198 1715

CFTR- DeltaF508- + CACAGUAGCUUACCCAUA 18

199 1716

CFTR- DeltaF508- + UCACAGUAGCUUACCCAUA 19

200 1717

CFTR- DeltaF508- + U UCACAGUAGCU UACCCAUA 20

201 692

CFTR- DeltaF508- + AUUCACAGUAGCUUACCCAUA 21

202 1718

CFTR- DeltaF508- + CAUUCACAGUAGCUUACCCAUA 22

203 1719

CFTR- DeltaF508- + CCAUUCACAGUAGCUUACCCAUA 23

204 1720

CFTR- DeltaF508- + UCCAUUCACAGUAGCUUACCCAUA 24

205 1721

CFTR- DeltaF508- + UGGUGCCAGGCAUAAUCC 18

206 1722

CFTR- DeltaF508- + AUGGUGCCAGGCAUAAUCC 19

207 1723

CFTR-

+ AAUGGUGCCAGGCAUAAUCC 20

DeltaF508-43 389

CFTR- DeltaF508- + UAAUGGUGCCAGGCAUAAUCC 21

208 1724

CFTR- DeltaF508- + UUAAUGGUGCCAGGCAUAAUCC 22

209 1725

CFTR- DeltaF508- + UUUAAUGGUGCCAGGCAUAAUCC 23

210 1726

222

5535.1 CFTR- DeltaF508- + CUU UAAUGGUGCCAGGCAUAAUCC 24

211 1727

CFTR- DeltaF508- + AUGGUGCCAGGCAUAAUC 18

212 1728

CFTR- DeltaF508- + AAUGGUGCCAGGCAUAAUC 19

213 1729

CFTR- DeltaF508- + UAAUGGUGCCAGGCAUAAUC 20

214 685

CFTR- DeltaF508- + U UAAUGGUGCCAGGCAUAAUC 21

215 1730

CFTR- DeltaF508- + U UUAAUGGUGCCAGGCAUAAUC 22

216 1731

CFTR- DeltaF508- + CUUUAAUGGUGCCAGGCAUAAUC 23

217 1732

CFTR- DeltaF508- + UCU UUAAUGGUGCCAGGCAUAAUC 24

218 1733

CFTR- DeltaF508- + ACCAUUAGAAGUGAAGUC 18

219 1734

CFTR- DeltaF508- + CACCAU U AG AAG UG AAG U C 19

220 1735

CFTR-

+ UCACCAUUAGAAGUGAAGUC 20

DeltaF508-45 434

CFTR- DeltaF508- + AUCACCAUUAGAAGUGAAGUC 21

221 1736

CFTR- DeltaF508- + AAUCACCAUUAGAAGUGAAGUC 22

222 1737

CFTR- DeltaF508- + UAAUCACCAUUAGAAGUGAAGUC 23

223 1738

CFTR-

+ AU AAU CACCAU U AG AAG UG AAG U C 24

DeltaF508- 1739

223

5535.1 CFTR- DeltaF508- + ACAGUAGCUUACCCAUAG 18

225 1740

CFTR- DeltaF508- + CACAGUAGCUUACCCAUAG 19

226 1741

CFTR-

+ UCACAGUAGCUUACCCAUAG 20

DeltaF508-47 429

CFTR- DeltaF508- + U UCACAGUAGCU UACCCAUAG 21

227 1742

CFTR- DeltaF508- + AUUCACAGUAGCUUACCCAUAG 22

228 1743

CFTR- DeltaF508- + CAUUCACAGUAGCUUACCCAUAG 23

229 1744

CFTR- DeltaF508- + CCAU UCACAGUAGCUUACCCAUAG 24

230 1745

CFTR- DeltaF508- + UAGACUAACCGAUUGAAU 18

231 1746

CFTR- DeltaF508- + GUAGACUAACCGAUUGAAU 19

232 1747

CFTR- DeltaF508- + UGUAGACUAACCGAUUGAAU 20

233 690

CFTR- DeltaF508- + AUGUAGACUAACCGAUUGAAU 21

234 1748

CFTR- DeltaF508- + UAUGUAGACUAACCGAU UGAAU 22

235 1749

CFTR- DeltaF508- + AUAUGUAGACUAACCGAUUGAAU 23

236 1750

CFTR- DeltaF508- + UAUAUGUAGACUAACCGAUUGAAU 24

237 1751

224

5535.1 CFTR- DeltaF508- + UUCUCCCAUAAUCACCAU 18

238 1752

CFTR- DeltaF508- + GU UCUCCCAUAAUCACCAU 19

239 1753

CFTR- DeltaF508- + AGUUCUCCCAUAAUCACCAU 20

240 679

CFTR- DeltaF508- + CAGU UCUCCCAUAAUCACCAU 21

241 1754

CFTR- DeltaF508- + CCAGU UCUCCCAUAAUCACCAU 22

242 1755

CFTR- DeltaF508- + UCCAGUUCUCCCAUAAUCACCAU 23

243 1756

CFTR- DeltaF508- + CUCCAGU UCUCCCAUAAUCACCAU 24

244 1757

CFTR- DeltaF508- + UGUAUCUAUAUUCAUCAU 18

245 1758

CFTR- DeltaF508- + CUGUAUCUAUAUUCAUCAU 19

246 1759

CFTR-

+ UCUGUAUCUAUAUUCAUCAU 20

DeltaF508-49 409

CFTR- DeltaF508- + UUCUGUAUCUAUAUUCAUCAU 21

247 1760

CFTR- DeltaF508- + CUUCUGUAUCUAUAUUCAUCAU 22

248 1761

CFTR- DeltaF508- + GCUUCUGUAUCUAUAU UCAUCAU 23

249 1762

CFTR- DeltaF508- + CGCUUCUGUAUCUAUAUUCAUCAU 24

250 1763

CFTR-

+ GCAUAAUCCAGGAAAACU 18

DeltaF508- 1764

225

5535.1 251

CFTR- DeltaF508- + GGCAUAAUCCAGGAAAACU 19

252 1765

CFTR- DeltaF508- + AGGCAUAAUCCAGGAAAACU 20

253 683

CFTR- DeltaF508- + CAGGCAUAAUCCAGGAAAACU 21

254 1766

CFTR- DeltaF508- + CCAGGCAUAAUCCAGGAAAACU 22

255 1767

CFTR- DeltaF508- + GCCAGGCAUAAUCCAGGAAAACU 23

256 1768

CFTR- DeltaF508- + UGCCAGGCAUAAUCCAGGAAAACU 24

257 1769

CFTR- DeltaF508- + UGUGCUUAAUUU UACCCU 18

258 1770

CFTR- DeltaF508- + CUGUGCUUAAU UUUACCCU 19

259 1771

CFTR- DeltaF508- + ACUGUGCUUAAUUUUACCCU 20

260 680

CFTR- DeltaF508- + CACUGUGCUUAAUUUUACCCU 21

261 1772

CFTR- DeltaF508- + CCACUGUGCUUAAUUUUACCCU 22

262 1773

CFTR- DeltaF508- + UCCACUGUGCUUAAUUUUACCCU 23

263 1774

CFTR- DeltaF508- + UUCCACUGUGCUUAAUUUUACCCU 24

264 1775

CFTR-

+ CACCAU U AG AAG UG AAG U 18

DeltaF508- 1776

226

5535.1 265

CFTR- DeltaF508- + U CACCAU U AG AAG UG AAG U 19

266 1777

CFTR- DeltaF508- + AUCACCAUUAGAAGUGAAGU 20

267 677

CFTR- DeltaF508- + AAUCACCAUUAGAAGUGAAGU 21

268 1778

CFTR- DeltaF508- + UAAUCACCAUUAGAAGUGAAGU 22

269 1779

CFTR- DeltaF508- + AUAAUCACCAUUAGAAGUGAAGU 23

270 1780

CFTR- DeltaF508- + CAUAAUCACCAUUAGAAGUGAAGU 24

271 1781

CFTR- DeltaF508- + AUAUAUAAUUUGGGUAGU 18

272 1782

CFTR- DeltaF508- + AAUAUAUAAUUUGGGUAGU 19

273 1783

CFTR- DeltaF508- + AAAUAUAUAAUUUGGGUAGU 20

274 688

CFTR- DeltaF508- + CAAAUAUAUAAUUUGGGUAGU 21

275 1784

CFTR- DeltaF508- + CCAAAUAUAUAAUUUGGGUAGU 22

276 1785

CFTR- DeltaF508- + GCCAAAUAUAUAAUUUGGGUAGU 23

277 1786

CFTR- DeltaF508- + AGCCAAAUAUAUAAUUUGGGUAGU 24

278 1787

CFTR-

- AUGGUGAUUAUGGGAGAA 18

DeltaF508- 1788

227

5535.1 279

CFTR- DeltaF508- - AAUGGUGAUUAUGGGAGAA 19

280 1789

CFTR- DeltaF508- - UAAUGGUGAUUAUGGGAGAA 20

281 659

CFTR- DeltaF508- - CUAAUGGUGAUUAUGGGAGAA 21

282 1790

CFTR- DeltaF508- - UCUAAUGGUGAUUAUGGGAGAA 22

283 1791

CFTR- DeltaF508- - UUCUAAUGGUGAUUAUGGGAGAA 23

284 1792

CFTR- DeltaF508- - CUUCUAAUGGUGAUUAUGGGAGAA 24

285 1793

CFTR- DeltaF508- - AGGG U AAAAU UAAGCACA 18

286 1794

CFTR- DeltaF508- - GAGGGUAAAAUUAAGCACA 19

287 1795

CFTR- DeltaF508- - AGAGGGU AAAAU UAAGCACA 20

288 662

CFTR- DeltaF508- - CAGAGGGUAAAAUUAAGCACA 21

289 1796

CFTR- DeltaF508- - UCAGAGGGU A A A A U U A AG CACA 22

290 1797

CFTR- DeltaF508- - U U CAG AGGG U AAAAU U AAG CACA 23

291 1798

CFTR- DeltaF508- - CUUCAGAGGGUAAAAU UAAGCACA 24

292 1799

CFTR-

- CUAUGAUGAAUAUAGAUA 18

DeltaF508- 1800

228

5535.1 293

CFTR- DeltaF508- - CCUAUGAUGAAUAUAGAUA 19

294 1801

CFTR- DeltaF508- - UCCUAUGAUGAAUAUAGAUA 20

295 667

CFTR- DeltaF508- - UUCCUAUGAUGAAUAUAGAUA 21

296 1802

CFTR- DeltaF508- - UUUCCUAUGAUGAAUAUAGAUA 22

297 1803

CFTR- DeltaF508- - GU UUCCUAUGAUGAAUAUAGAUA 23

298 1804

CFTR- DeltaF508- - UGUUUCCUAUGAUGAAUAUAGAUA 24

299 1805

CFTR- DeltaF508- - UUAUGCCUGGCACCAUUA 18

300 1806

CFTR- DeltaF508- - AUUAUGCCUGGCACCAU UA 19

301 1807

CFTR- DeltaF508- - GAUUAUGCCUGGCACCAUUA 20

302 665

CFTR- DeltaF508- - GGAUUAUGCCUGGCACCAUUA 21

303 1808

CFTR- DeltaF508- - UGGAUUAUGCCUGGCACCAUUA 22

304 1809

CFTR- DeltaF508- - CUGGAUUAUGCCUGGCACCAUUA 23

305 1810

CFTR- DeltaF508- - CCUGGAUUAUGCCUGGCACCAUUA 24

306 1811

CFTR-

- CACUUCUAAUGGUGAUUA 18

DeltaF508- 1812

229

5535.1 307

CFTR- DeltaF508- - UCACUUCUAAUGGUGAUUA 19

308 1813

CFTR-

- UUCACUUCUAAUGGUGAUUA 20

DeltaF508-39 421

CFTR- DeltaF508- - CUUCACUUCUAAUGGUGAUUA 21

309 1814

CFTR- DeltaF508- - ACUUCACUUCUAAUGGUGAUUA 22

310 1815

CFTR- DeltaF508- - GACUUCACUUCUAAUGGUGAUUA 23

311 1816

CFTR- DeltaF508- - AGACUUCACUUCUAAUGGUGAUUA 24

312 1817

CFTR- DeltaF508- - UCAUCAAAGCAUGCCAAC 18

313 1818

CFTR- DeltaF508- - G U C A U C A A AG CAUGCCAAC 19

314 1819

CFTR- DeltaF508- - CGUCAUCAAAGCAUGCCAAC 20

315 668

CFTR- DeltaF508- - GCGUCAUCAAAGCAUGCCAAC 21

316 1820

CFTR- DeltaF508- - AGCGUCAUCAAAGCAUGCCAAC 22

317 1821

CFTR- DeltaF508- - AAG CG U CAU C AAAG C AU G CCAAC 23

318 1822

CFTR- DeltaF508- - G AAG CG U CAU CAAAGCAUG CCAAC 24

319 1823

CFTR- DeltaF508- - UGGUGAUUAUGGGAGAAC 18

320 1824

230

5535.1 CFTR- DeltaF508- - AUGGUGAUUAUGGGAGAAC 19

321 1825

CFTR-

- AAUGGUGAUUAUGGGAGAAC 20

DeltaF508-40 423

CFTR- DeltaF508- - UAAUGGUGAUUAUGGGAGAAC 21

322 1826

CFTR- DeltaF508- - CUAAUGGUGAUUAUGGGAGAAC 22

323 1827

CFTR- DeltaF508- - UCUAAUGGUGAUUAUGGGAGAAC 23

324 1828

CFTR- DeltaF508- - UUCUAAUGGUGAUUAUGGGAGAAC 24

325 1829

CFTR- DeltaF508- - AUUGGAGGCAAGUGAAUC 18

326 1830

CFTR- DeltaF508- - AAUUGGAGGCAAGUGAAUC 19

327 1831

CFTR- DeltaF508- - UAAUUGGAGGCAAGUGAAUC 20

328 655

CFTR- DeltaF508- - GGG UAAAAU UAAG CACAG 18

329 1832

CFTR- DeltaF508- - AG G G U A A A A U U A AG C AC AG 19

330 1833

CFTR-

- GAGGG UAAAAU UAAGCACAG 20

DeltaF508-12 387

CFTR- DeltaF508- - AG AG G G U A A A A U U A AG CACAG 21

331 1834

CFTR- DeltaF508- - CAGAGGGUAAAAUUAAGCACAG 22

332 1835

CFTR- DeltaF508- - UCAGAGGGUAAAAUUAAGCACAG 23

333 1836

231

5535.1 CFTR- DeltaF508- - U UCAGAGGGUAAAAUUAAGCACAG 24

334 1837

CFTR- DeltaF508- - UCAAAGCAUGCCAACUAG 18

335 1838

CFTR- DeltaF508- - A U C A A AG C A U G C C A AC U AG 19

336 1839

CFTR- DeltaF508- - CAUCAAAGCAUGCCAACUAG 20

337 669

CFTR- DeltaF508- - U C A U C A A AG C A U G C C A AC U AG 21

338 1840

CFTR- DeltaF508- - GUCAUCAAAGCAUGCCAACUAG 22

339 1841

CFTR- DeltaF508- - CGUCAUCAAAGCAUGCCAACUAG 23

340 1842

CFTR- DeltaF508- - GCGUCAUCAAAGCAUGCCAACUAG 24

341 1843

CFTR- DeltaF508- - UUCUAAUGGUGAUUAUGG 18

342 1844

CFTR- DeltaF508- - CUUCUAAUGGUGAUUAUGG 19

343 1845

CFTR- DeltaF508- - ACUUCUAAUGGUGAU UAUGG 20

344 658

CFTR- DeltaF508- - CACUUCUAAUGGUGAU UAUGG 21

345 1846

CFTR- DeltaF508- - UCACUUCUAAUGGUGAUUAUGG 22

346 1847

CFTR- DeltaF508- - UUCACUUCUAAUGGUGAUUAUGG 23

347 1848

232

5535.1 CFTR- DeltaF508- - CUUCACUUCUAAUGGUGAUUAUGG 24

348 1849

CFTR- DeltaF508- - AACUUUUUGAUUAUGCAU 18

349 1850

CFTR- DeltaF508- - AAACUUUUUGAUUAUGCAU 19

350 1851

CFTR- DeltaF508- - AAAACUUUUUGAUUAUGCAU 20

351 672

CFTR- DeltaF508- - GAAAACUUUUUGAUUAUGCAU 21

352 1852

CFTR- DeltaF508- - UGAAAACUUUUUGAUUAUGCAU 22

353 1853

CFTR- DeltaF508- - GUGAAAACUUUUUGAUUAUGCAU 23

354 1854

CFTR- DeltaF508- - UGUGAAAACUUUUUGAUUAUGCAU 24

355 1855

CFTR- DeltaF508- - GAAGAGGUAAGAAACUAU 18

356 1856

CFTR- DeltaF508- - AGAAGAGGUAAGAAACUAU 19

357 1857

CFTR- DeltaF508- - UAGAAGAGGUAAGAAACUAU 20

358 671

CFTR- DeltaF508- - CUAGAAGAGGUAAGAAACUAU 21

359 1858

CFTR- DeltaF508- - ACU AGAAGAGGUAAGAAACUAU 22

360 1859

CFTR- DeltaF508- - AACUAGAAGAGGUAAGAAACUAU 23

361 1860

233

5535.1 CFTR- DeltaF508- - CAACUAGAAGAGGUAAGAAACUAU 24

362 1861

CFTR- DeltaF508- - ACU UCUAAUGGUGAUUAU 18

363 1862

CFTR- DeltaF508- - CACUUCUAAUGGUGAUUAU 19

364 1863

CFTR-

- UCACUUCUAAUGGUGAUUAU 20

DeltaF508-51 422

CFTR- DeltaF508- - UUCACUUCUAAUGGUGAUUAU 21

365 1864

CFTR- DeltaF508- - CUUCACUUCUAAUGGUGAUUAU 22

366 1865

CFTR- DeltaF508- - ACU UCACUUCUAAUGGUGAUUAU 23

367 1866

CFTR- DeltaF508- - GACU UCACUUCUAAUGGUGAUUAU 24

368 1867

CFTR- DeltaF508- - AUGCCAACUAGAAGAGGU 18

369 1868

CFTR- DeltaF508- - CAUGCCAACUAGAAGAGGU 19

370 1869

CFTR- DeltaF508- - GCAUGCCAACUAGAAGAGGU 20

371 670

CFTR- DeltaF508- - AGCAUGCCAACUAGAAGAGGU 21

372 1870

CFTR- DeltaF508- - AAGCAUGCCAACUAGAAGAGGU 22

373 1871

CFTR- DeltaF508- - A A AG CAUGCCAACUAGAAGAGGU 23

374 1872

CFTR-

- CAAAGCAUGCCAACUAGAAGAGGU 24

DeltaF508- 1873

234

5535.1 375

CFTR- DeltaF508- - UCACU UCUAAUGGUGAUU 18

376 1874

CFTR- DeltaF508- - UUCACUUCUAAUGGUGAUU 19

377 1875

CFTR- DeltaF508- - CUUCACUUCUAAUGGUGAUU 20

378 657

CFTR- DeltaF508- - ACUUCACUUCUAAUGGUGAUU 21

379 1876

CFTR- DeltaF508- - GACUUCACUUCUAAUGGUGAUU 22

380 1877

CFTR- DeltaF508- - AGACUUCACUUCUAAUGGUGAUU 23

381 1878

CFTR- DeltaF508- - CAGACU UCACUUCUAAUGGUGAUU 24

382 1879

CFTR- DeltaF508- - UGGGAGAACUGGAGCCUU 18

383 1880

CFTR- DeltaF508- - AUGGGAGAACUGGAGCCUU 19

384 1881

CFTR- DeltaF508- - UAUGGGAGAACUGGAGCCUU 20

385 660

CFTR- DeltaF508- - UUAUGGGAGAACUGGAGCCUU 21

386 1882

CFTR- DeltaF508- - AUUAUGGGAGAACUGGAGCCUU 22

387 1883

CFTR- DeltaF508- - GAUUAUGGGAGAACUGGAGCCUU 23

388 1884

CFTR-

- UGAUUAUGGGAGAACUGGAGCCUU 24

DeltaF508- 1885

235

5535.1

Table 12A provides exemplary targeting domains for correcting a mutation (e.g., deltaF508) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., deltaF508), have a high level of orthogonality and start with a 5'G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 12A

Table 12B provides exemplary targeting domains for correcting a mutation (e.g., deltaF508) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., deltaF508) and have a high level of orthogonality. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 12B

236

5535.1 CFTR-

+ CUUACCUCUUCUAGUUG 17

DeltaF508-394 1887

CFTR-

- UU UCCAGACUUCACUUCUAA 20

DeltaF508-34 420

CFTR-

- UGGAGGCAAGUGAAUCCUGA 20

DeltaF508-395 917

CFTR-

+ U UCUAGUUGGCAUGCUUUGA 20

DeltaF508-396 1888

CFTR-

+ AGGUCAUUAUCAAAUCACGC 20

DeltaF508-397 920

CFTR-

- UAAGAAACUAUGUGAAAACU 20

DeltaF508-398 919

Table 12C provides exemplary targeting domains for correcting a mutation (e.g., deltaF508) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., deltaF508). It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 12C

237

5535.1 Table 13A provides exemplary targeting domains for correcting a mutation (e.g., G542X) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., G542X), have a high level of orthogonality and start with a 5'G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break

(Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 13A

Table 13B provides exemplary targeting domains for correcting a mutation (e.g., G542X) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., G542X) and have a high level of orthogonality. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 13B

238

5535.1 CFTR-G542X-

- UAUAUGAUUACAUUAGA 17

12 485

CFTR-G542X-

- AAAAUCCUGGGGUUUUA 17

13 493

CFTR-G542X-

+ ACUAGCCAUAAAACCCC 17

14 459

CFTR-G542X-

- UGGGGUUUUAUGGCUAG 17

15 494

CFTR-G542X-

- AUAGUUCUUUGAGAAGG 17

16 1892

CFTR-G542X-

+ AUGCUCAAUCUGAAUUUGAA 20

17 484

CFTR-G542X-

- UGAUAUAUGAUUACAUUAGA 20

18 471

CFTR-G542X-

+ CCCACUAGCCAUAAAACCCC 20

19 455

CFTR-G542X-

- UUCUGGAAUUGAAAAAAUCC 20

20 477

CFTR-G542X-

- CUGGAAUUGAAAAAAUCCUG 20

21 479

CFTR-G542X-

- CAAGGUGAAUAACUAAU UAU 20

22 475

CFTR-G542X-

- CCUGGGGU UUUAUGGCUAGU 20

23 481

Table 13C provides exemplary targeting domains for correcting a mutation (e.g., G542X) in the CFTR gene selected according to the third tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., G542X) and start with a 5'G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through

complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 13C

239

5535.1 25

CFTR-G542X-

- GGAAUUGAAAAAAUCCU 17

26 467

CFTR-G542X-

- GACAAUAUAGUUCUUUGAGA 20

27 1893

CFTR-G542X-

- GAAAAAAUCCUGGGGUUUUA 20

28 463

Table 13D provides exemplary targeting domains for correcting a mutation (e.g., G542X) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., G542X). It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 13D

240

5535.1 CFTR-G542X-

+ AUUGUCUUUCUCUGCAAACU 20

40 483

CFTR-G542X-

- UCUGGAAUUGAAAAAAUCCU 20

41 478

CFTR-G542X-

- ACUCUCUAAUU UUCUAU UUU 20

42 472

Table 14A provides exemplary targeting domains for correcting a mutation (e.g., G542X) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., G542X), have a high level of orthogonality, start with a 5'G, and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 14A

241

5535.1 53

Table 14B provides exemplary targeting domains for correcting a mutation (e.g., G542X) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., G542X), have a high level of orthogonality and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 14B

242

5535.1 CFTR-G542X-

+ U UAACCCACUAGCCAUAAAACCC 23

67 1918

CFTR-G542X-

+ CUUAACCCACUAGCCAUAAAACCC 24

68 1919

CFTR-G542X-

+ ACUUUUAGUAUGCUCAAU 18

69 1920

CFTR-G542X-

+ CACUUUUAGUAUGCUCAAU 19

70 1921

CFTR-G542X-

+ UCACUUUUAGUAUGCUCAAU 20

71 756

CFTR-G542X-

+ AGUCACUUUUAGUAUGCUCAAU 22

72 1922

CFTR-G542X-

+ AGAGUCACUUUUAGUAUGCUCAAU 24

73 1923

CFTR-G542X-

- CCUGGGGU UUUAUGGCUA 18

74 1924

CFTR-G542X-

- UCCUGGGGUUUUAUGGCUA 19

75 1925

CFTR-G542X-

- AUCCUGGGGUUUUAUGGCUA 20

76 750

CFTR-G542X-

- AAUCCUGGGGUUUUAUGGCUA 21

77 1926

CFTR-G542X-

- AAAUCCUGGGGUUUUAUGGCUA 22

78 1927

CFTR-G542X-

- AAAAUCCUGGGGUUUUAUGGCUA 23

79 1928

CFTR-G542X-

- AAAAAUCCUGGGGUUUUAUGGCUA 24

80 1929

CFTR-G542X-

- UGAGUGGAGGUCAACGAGC 19

81 1930

CFTR-G542X-

- CUGAGUGGAGGUCAACGAGC 20

82 745

CFTR-G542X-

- UGCUUUAUAUUCUGUUUC 18

83 1931

CFTR-G542X-

- UUGCUUUAUAUUCUGU UUC 19

84 1932

CFTR-G542X-

- AUUGCUUUAUAUUCUGUUUC 20

35 476

CFTR-G542X-

- UAUUGCUUUAUAUUCUGUUUC 21

85 1933

CFTR-G542X-

- CUAUUGCUUUAUAUUCUGUUUC 22

86 1934

CFTR-G542X- - UCUAUUGCU UUAUAUUCUGUUUC 23 1935

243

5535.1 87

CFTR-G542X-

- CUCUAUUGCUUUAUAU UCUGUUUC 24

88 1936

CFTR-G542X-

- AAGAAUUUCUUUAGCAAG 18

89 1937

CFTR-G542X-

- CAAGAAUUUCUUUAGCAAG 19

90 1938

CFTR-G542X-

- AGCAAGAAUUUCUUUAGCAAG 21

91 1939

CFTR-G542X-

- CG AG CAAGAAU U U CU U U AG CAAG 23

92 1940

CFTR-G542X-

- ACG AG CAAGAAU U U CU U UAGCAAG 24

93 1941

CFTR-G542X-

- UU UUAUGGCUAGUGGGUU 18

94 1942

CFTR-G542X-

- UGGGGUUUUAUGGCUAGUGGGUU 23

95 1943

CFTR-G542X-

- CUGGGGUUUUAUGGCUAGUGGGUU 24

96 1944

Table 14C provides exemplary targeting domains for correcting a mutation (e.g., G542X) in the CFTR gene selected according to the third tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., G542X), start with a 5'G and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 14C

244

5535.1 CFTR-G542X-

- GACAAUAUAGUUCUUUGAGAAGG 23

101 1949

Table 14D provides exemplary targeting domains for correcting a mutation (e.g., G542X) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., G542X), and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 14D

245

5535.1 114

CFTR-G542X-

- UCUUUGAGAAGGUGGAAUCACA 22

115 1962

CFTR-G542X-

- UUCUUUGAGAAGGUGGAAUCACA 23

116 1963

CFTR-G542X-

- CUGGAAUUGAAAAAAUCC 18

117 1964

CFTR-G542X-

- UCUGGAAUUGAAAAAAUCC 19

118 1965

CFTR-G542X-

- UUCUGGAAUUGAAAAAAUCC 20

20 477

CFTR-G542X-

- UUUCUGGAAUUGAAAAAAUCC 21

119 1966

CFTR-G542X-

- UGUUUCUGGAAUUGAAAAAAUCC 23

120 1967

CFTR-G542X-

- CUGUUUCUGGAAUUGAAAAAAUCC 24

121 1968

CFTR-G542X-

- ACUGAGUGGAGGUCAACGAGC 21

122 1969

CFTR-G542X-

- CACUGAGUGGAGGUCAACGAGC 22

123 1970

CFTR-G542X-

- ACACUGAGUGGAGGUCAACGAGC 23

124 1971

CFTR-G542X-

- CACACUGAGUGGAGGUCAACGAGC 24

125 1972

CFTR-G542X-

- UAUAGUUCUUUGAGAAGG 18

126 1973

CFTR-G542X-

- AUAUAGUUCUUUGAGAAGG 19

127 1974

CFTR-G542X-

- AAUAUAGUUCUUUGAGAAGG 20

37 1897

CFTR-G542X-

- CAAUAUAGUUCUUUGAGAAGG 21

128 1975

CFTR-G542X-

- ACAAUAUAGUUCUUUGAGAAGG 22

129 1976

CFTR-G542X-

- AG ACAAU AU AG U U CU U UG AG AAGG 24

130 1977

Table 14E provides exemplary targeting domains for correcting a mutation (e.g., G542X) in the CFTR gene selected according to the fifth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., G542X), and PAM is NNGRRV. It is contemplated herein

246

5535.1 that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with ; aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 14E

247

5535.1 147

CFTR-G542X-

+ CAGUGUGAUUCCACCUUCUCA 21

148 1993

CFTR-G542X-

+ UCAGUGUGAUUCCACCUUCUCA 22

149 1994

CFTR-G542X-

+ CUCAGUGUGAUUCCACCUUCUCA 23

150 1995

CFTR-G542X-

+ ACUCAGUGUGAUUCCACCUUCUCA 24

151 1996

CFTR-G542X-

+ ACAGAAUAUAAAGCAAUA 18

152 1997

CFTR-G542X-

+ AACAGAAUAUAAAGCAAUA 19

153 1998

CFTR-G542X-

+ A A AC AG A A U A U A A AG C A A U A 20

154 764

CFTR-G542X-

+ G A A AC AG A A U A U A A AG C A A U A 21

155 1999

CFTR-G542X-

+ AGAAACAGAAUAUAAAGCAAUA 22

156 2000

CFTR-G542X-

+ C AG A A AC AG A A U A U A A AG C A A U A 23

157 2001

CFTR-G542X-

+ CCAGAAACAGAAUAUAAAGCAAUA 24

158 2002

CFTR-G542X-

+ UAGUUAUUCACCUUGCUA 18

159 2003

CFTR-G542X-

+ UUAGUUAUUCACCUUGCUA 19

160 2004

CFTR-G542X-

+ AUUAGUUAUUCACCUUGCUA 20

161 762

CFTR-G542X-

+ AAUUAGUUAUUCACCU UGCUA 21

162 2005

CFTR-G542X-

+ UAAUUAGUUAUUCACCUUGCUA 22

163 2006

CFTR-G542X-

+ AUAAUUAGUUAUUCACCUUGCUA 23

164 2007

CFTR-G542X-

+ AAUAAUUAGUUAUUCACCUUGCUA 24

165 2008

CFTR-G542X-

+ UUGUCUUUCUCUGCAAAC 18

166 2009

CFTR-G542X-

+ AUUGUCUUUCUCUGCAAAC 19

167 2010

CFTR-G542X-

+ UAUUGUCUUUCUCUGCAAAC 20

168 760

248

5535.1 CFTR-G542X-

+ AUAUUGUCUUUCUCUGCAAAC 21

169 2011

CFTR-G542X-

+ UAUAUUGUCUUUCUCUGCAAAC 22

170 2012

CFTR-G542X-

+ CUAUAUUGUCU UUCUCUGCAAAC 23

171 2013

CFTR-G542X-

+ ACUAUAUUGUCUUUCUCUGCAAAC 24

172 2014

CFTR-G542X-

+ CCAGGAUUUUU UCAAU UC 18

173 2015

CFTR-G542X-

+ CCCAGGAUUU UUUCAAU UC 19

174 2016

CFTR-G542X-

+ CCCCAGGAU UUUUUCAAUUC 20

175 767

CFTR-G542X-

+ ACCCCAGGAUUUUUUCAAUUC 21

176 2017

CFTR-G542X-

+ AACCCCAGGAUUUUUUCAAUUC 22

177 2018

CFTR-G542X-

+ AAACCCCAGG AU UUUUUCAAUUC 23

178 2019

CFTR-G542X-

+ AAAACCCCAGG AU U U U U U CAAU U C 24

179 2020

CFTR-G542X-

+ CUAUUGCUUUAACCACAG 18

180 2021

CFTR-G542X-

+ ACUAUUGCUUUAACCACAG 19

181 2022

CFTR-G542X-

+ CACUAUUGCUUUAACCACAG 20

182 754

CFTR-G542X-

+ ACACUAUUGCUU UAACCACAG 21

183 2023

CFTR-G542X-

+ CACACUAUUGCUUUAACCACAG 22

184 2024

CFTR-G542X-

+ U CACACU AU UG CU U U AACCACAG 23

185 2025

CFTR-G542X-

+ AUCACACUAUUGCUUUAACCACAG 24

186 2026

CFTR-G542X-

+ U U ACCAAAAAU AG AAAAU 18

187 2027

CFTR-G542X-

+ AUUACCAAAAAUAGAAAAU 19

188 2028

CFTR-G542X-

+ UAU U ACCAAAAAU AGAAAAU 20

189 758

CFTR-G542X- + CU AU U ACCAAAAAU AG AAAAU 21 2029

249

5535.1 190

CFTR-G542X-

+ CCU AUU ACCAAAAAU AGAAAAU 22

191 2030

CFTR-G542X-

+ UCCUAUUACCAAAAAUAGAAAAU 23

192 2031

CFTR-G542X-

+ G U CCU AU U ACCAAAAAU AG AAAAU 24

193 2032

CFTR-G542X-

+ AGUAUGCUCAAUCUGAAU 18

194 2033

CFTR-G542X-

+ UAGUAUGCUCAAUCUGAAU 19

195 2034

CFTR-G542X-

+ U UAGUAUGCUCAAUCUGAAU 20

196 755

CFTR-G542X-

+ U UUAGUAUGCUCAAUCUGAAU 21

197 2035

CFTR-G542X-

+ U UUUAGUAUGCUCAAUCUGAAU 22

198 2036

CFTR-G542X-

+ CUU UUAGUAUGCUCAAUCUGAAU 23

199 2037

CFTR-G542X-

+ ACUUUUAGUAUGCUCAAUCUGAAU 24

200 2038

CFTR-G542X-

+ UGUCUUUCUCUGCAAACU 18

201 2039

CFTR-G542X-

+ UUGUCUUUCUCUGCAAACU 19

202 2040

CFTR-G542X-

+ AUUGUCUUUCUCUGCAAACU 20

40 483

CFTR-G542X-

+ UAUUGUCUUUCUCUGCAAACU 21

203 2041

CFTR-G542X-

+ AUAUUGUCUUUCUCUGCAAACU 22

204 2042

CFTR-G542X-

+ UAUAUUGUCUUUCUCUGCAAACU 23

205 2043

CFTR-G542X-

+ CUAUAUUGUCU UUCUCUGCAAACU 24

206 2044

CFTR-G542X-

+ U U AACCACAG UUGAAAU U 18

207 2045

CFTR-G542X-

+ U U U AACCACAG UUGAAAU U 19

208 2046

CFTR-G542X-

+ CUUU AACCACAG UUGAAAU U 20

209 753

CFTR-G542X-

+ G CU U U AACCACAG UUGAAAU U 21

210 2047

250

5535.1 CFTR-G542X-

+ UGCUUUAACCACAGUUGAAAUU 22

211 2048

CFTR-G542X-

+ U UGCUUUAACCACAGUUGAAAUU 23

212 2049

CFTR-G542X-

+ AU UG CU U U AACCACAG U UG AAAU U 24

213 2050

CFTR-G542X-

- UAUAUUCUGUUUCUGGAA 18

214 2051

CFTR-G542X-

- UUAUAUUCUGUUUCUGGAA 19

215 2052

CFTR-G542X-

- UU UAUAUUCUGUUUCUGGAA 20

216 748

CFTR-G542X-

- CUUUAUAUUCUGUUUCUGGAA 21

217 2053

CFTR-G542X-

- GCUU UAUAUUCUGUUUCUGGAA 22

218 2054

CFTR-G542X-

- UGCU UUAUAUUCUGUU UCUGGAA 23

219 2055

CFTR-G542X-

- UUGCUUUAUAUUCUGU UUCUGGAA 24

220 2056

CFTR-G542X-

- AAAUUGCAUUUGAAAUAA 18

221 2057

CFTR-G542X-

- UAAAUUGCAUUUGAAAUAA 19

222 2058

CFTR-G542X-

- AUAAAUUGCAUUUGAAAUAA 20

34 1896

CFTR-G542X-

- AUUUUCUAUUU UUGGUAA 18

223 2059

CFTR-G542X-

- AAUUUUCUAUUUUUGGUAA 19

224 2060

CFTR-G542X-

- UAAUUUUCUAUUUUUGGUAA 20

225 736

CFTR-G542X-

- CUAAUUUUCUAU UUUUGGUAA 21

226 2061

CFTR-G542X-

- UCUAAUUUUCUAUUUUUGGUAA 22

227 2062

CFTR-G542X-

- CUCUAAUUUUCUAUUUUUGGUAA 23

228 2063

CFTR-G542X-

- UCUCUAAUUUUCUAUUUUUGGUAA 24

229 2064

CFTR-G542X-

- GACAUCUCCAAGUUUGCA 18

230 2065

CFTR-G542X- - GGACAUCUCCAAGU UUGCA 19 2066

251

5535.1 231

CFTR-G542X-

- AGGACAUCUCCAAGUUUGCA 20

232 738

CFTR-G542X-

- UAGGACAUCUCCAAGUU UGCA 21

233 2067

CFTR-G542X-

- AUAGGACAUCUCCAAGU UUGCA 22

234 2068

CFTR-G542X-

- AAUAGGACAUCUCCAAGUUUGCA 23

235 2069

CFTR-G542X-

- UAAUAGGACAUCUCCAAGUUUGCA 24

236 2070

CFTR-G542X-

- CACACUGAGUGGAGGUCA 18

237 2071

CFTR-G542X-

- UCACACUGAGUGGAGGUCA 19

238 2072

CFTR-G542X-

- AUCACACUGAGUGGAGGUCA 20

239 744

CFTR-G542X-

- AAUCACACUGAGUGGAGGUCA 21

240 2073

CFTR-G542X-

- GAAUCACACUGAGUGGAGGUCA 22

241 2074

CFTR-G542X-

- GGAAUCACACUGAGUGGAGGUCA 23

242 2075

CFTR-G542X-

- UGGAAUCACACUGAGUGGAGGUCA 24

243 2076

CFTR-G542X-

- GUGCCU UUCAAAUUCAGA 18

244 2077

CFTR-G542X-

- UGUGCCUUUCAAAUUCAGA 19

245 2078

CFTR-G542X-

- AUGUGCCUU UCAAAUUCAGA 20

246 735

CFTR-G542X-

- GAUGUGCCUU UCAAAU UCAGA 21

247 2079

CFTR-G542X-

- AGAUGUGCCUUUCAAAUUCAGA 22

248 2080

CFTR-G542X-

- AAGAUGUGCCUUUCAAAUUCAGA 23

249 2081

CFTR-G542X-

- GAAGAUGUGCCUUUCAAAUUCAGA 24

250 2082

CFTR-G542X-

- AUAUAUGAUUACAUUAGA 18

251 2083

CFTR-G542X-

- GAUAUAUGAUUACAUUAGA 19

252 2084

252

5535.1 CFTR-G542X-

- UGAUAUAUGAUUACAUUAGA 20

18 471

CFTR-G542X-

- GUGAUAUAUGAUUACAUUAGA 21

253 2085

CFTR-G542X-

- UGUGAUAUAUGAUUACAUUAGA 22

254 2086

CFTR-G542X-

- GUGUGAUAUAUGAUUACAUUAGA 23

255 2087

CFTR-G542X-

- AGUGUGAUAUAUGAUUACAUUAGA 24

256 2088

CFTR-G542X-

- AAGGUGGAAUCACACUGA 18

257 2089

CFTR-G542X-

- GAAGGUGGAAUCACACUGA 19

258 2090

CFTR-G542X-

- AGAAGGUGGAAUCACACUGA 20

259 743

CFTR-G542X-

- GAGAAGGUGGAAUCACACUGA 21

260 2091

CFTR-G542X-

- UGAGAAGGUGGAAUCACACUGA 22

261 2092

CFTR-G542X-

- UUGAGAAGGUGGAAUCACACUGA 23

262 2093

CFTR-G542X-

- UU UGAGAAGGUGGAAUCACACUGA 24

263 2094

CFTR-G542X-

- UAAAUUGCAUUUGAAAUA 18

264 2095

CFTR-G542X-

- AUAAAUUGCAUUUGAAAUA 19

265 2096

CFTR-G542X-

- AAUAAAUUGCAUUUGAAAUA 20

266 2097

CFTR-G542X-

- UCUGGAAUUGAAAAAAUC 18

267 2098

CFTR-G542X-

- UUCUGGAAUUGAAAAAAUC 19

268 2099

CFTR-G542X-

- UUUCUGGAAUUGAAAAAAUC 20

269 749

CFTR-G542X-

- GU UUCUGGAAUUGAAAAAAUC 21

270 2100

CFTR-G542X-

- UGUUUCUGGAAUUGAAAAAAUC 22

271 2101

CFTR-G542X-

- CUGU UUCUGGAAUUGAAAAAAUC 23

272 2102

CFTR-G542X- - UCUGUUUCUGGAAUUGAAAAAAUC 24 2103

253

5535.1 273

CFTR-G542X-

- AUAUAGUUCUUUGAGAAG 18

274 2104

CFTR-G542X-

- AAUAUAGUUCUUUGAGAAG 19

275 2105

CFTR-G542X-

- CAAUAUAGUUCUUUGAGAAG 20

276 2106

CFTR-G542X-

- ACAAUAUAGUUCUUUGAGAAG 21

277 2107

CFTR-G542X-

- GACAAUAUAGUUCUUUGAGAAG 22

278 2108

CFTR-G542X-

- AG ACAAU AU AG U U CU U UG AG AAG 23

279 2109

CFTR-G542X-

- AAG ACAAU AU AG U U CU U UG AG AAG 24

280 2110

CFTR-G542X-

- AGGUGGAAUCACACUGAG 18

281 2111

CFTR-G542X-

- AAGGUGGAAUCACACUGAG 19

282 2112

CFTR-G542X-

- GAAGGUGGAAUCACACUGAG 20

8 461

CFTR-G542X-

- AGAAGGUGGAAUCACACUGAG 21

283 2113

CFTR-G542X-

- GAGAAGGUGGAAUCACACUGAG 22

284 2114

CFTR-G542X-

- UGAGAAGGUGGAAUCACACUGAG 23

285 2115

CFTR-G542X-

- UUGAGAAGGUGGAAUCACACUGAG 24

286 2116

CFTR-G542X-

- GAUAUAUGAUUACAUUAG 18

287 2117

CFTR-G542X-

- UGAUAUAUGAUUACAU UAG 19

288 2118

CFTR-G542X-

- GUGAUAUAUGAUUACAUUAG 20

289 734

CFTR-G542X-

- UGUGAUAUAUGAUUACAUUAG 21

290 2119

CFTR-G542X-

- GUGUGAUAUAUGAUUACAUUAG 22

291 2120

CFTR-G542X-

- AGUGUGAUAUAUGAUUACAUUAG 23

292 2121

CFTR-G542X-

- UAGUGUGAUAUAUGAUUACAUUAG 24

293 2122

254

5535.1 CFTR-G542X-

- AGGACAUCUCCAAGUUUG 18

294 2123

CFTR-G542X-

- UAGGACAUCUCCAAGUU UG 19

295 2124

CFTR-G542X-

- AUAGGACAUCUCCAAGU UUG 20

296 737

CFTR-G542X-

- AAUAGGACAUCUCCAAGUUUG 21

297 2125

CFTR-G542X-

- UAAUAGGACAUCUCCAAGUUUG 22

298 2126

CFTR-G542X-

- GU AAUAGGACAUCUCCAAGUUUG 23

299 2127

CFTR-G542X-

- GGUAAUAGGACAUCUCCAAGUUUG 24

300 2128

CFTR-G542X-

- UGUGAUAUAUGAUUACAU 18

301 2129

CFTR-G542X-

- GUGUGAUAUAUGAUUACAU 19

302 2130

CFTR-G542X-

- AGUGUGAUAUAUGAUUACAU 20

303 733

CFTR-G542X-

- UAGUGUGAUAUAUGAU UACAU 21

304 2131

CFTR-G542X-

- AUAGUGUGAUAUAUGAUUACAU 22

305 2132

CFTR-G542X-

- AAUAGUGUGAUAUAUGAUUACAU 23

306 2133

CFTR-G542X-

- CAAUAGUGUGAUAUAUGAUUACAU 24

307 2134

CFTR-G542X-

- GAAAGACAAUAUAGUUCU 18

308 2135

CFTR-G542X-

- AG AAAG ACAAU AU AG U U CU 19

309 2136

CFTR-G542X-

- GAGAAAGACAAUAUAGUUCU 20

310 453

CFTR-G542X-

- AG AG AAAG ACAAU AU AG U U CU 21

311 2137

CFTR-G542X-

- CAGAGAAAGACAAUAUAGUUCU 22

312 2138

CFTR-G542X-

- GCAG AG AAAG ACAAU AU AG U U CU 23

313 2139

CFTR-G542X-

- UGCAGAGAAAGACAAUAUAGUUCU 24

314 2140

CFTR-G542X- - AAG ACAAU AU AG U U CU U U 18 2141

255

5535.1 315

CFTR-G542X-

- AAAGACAAUAUAGUUCUUU 19

316 2142

CFTR-G542X-

- GAAAGACAAUAUAGUUCUUU 20

317 2143

CFTR-G542X-

- AG AAAG ACAAU AU AG U U CU U U 21

318 2144

CFTR-G542X-

- GAGAAAGACAAUAUAGUUCUUU 22

319 2145

CFTR-G542X-

- AG AG AAAG ACAAU AU AG U U CU U U 23

320 2146

CFTR-G542X-

- CAG AG AAAG ACAAU AU AG U U CU U U 24

321 2147

CFTR-G542X-

- UUGCUUUAUAUUCUGUUU 18

322 2148

CFTR-G542X-

- AUUGCUUUAUAUUCUGUUU 19

323 2149

CFTR-G542X-

- UAUUGCUUUAUAUUCUGUUU 20

324 747

CFTR-G542X-

- CUAUUGCUUUAUAUUCUGUUU 21

325 2150

CFTR-G542X-

- UCUAUUGCUUUAUAUUCUGUUU 22

326 2151

CFTR-G542X-

- CUCUAUUGCUUUAUAUUCUGUUU 23

327 2152

CFTR-G542X-

- UCUCUAUUGCUUUAUAUUCUGUUU 24

328 2153

Table 15A provides exemplary targeting domains for correcting a mutation (e.g., G542X) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., G542X), have a high level of orthogonality and start with a 5'G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 15A

256

5535.1 CFTR-G542X-

+ GUAAUCAUAUAUCACAC 17

329 2154

CFTR-G542X-

- GGU UAAAGCAAUAGUGUGAU 20

330 927

Table 15B provides exemplary targeting domains for correcting a mutation (e.g., G542X) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., G542X) and have a high level of orthogonality. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 15B

Table 15C provides exemplary targeting domains for correcting a mutation (e.g., G542X) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., G542X). It is contemplated herein that in an

257

5535.1 embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break

(Cas9 nickase).

Table 15C

Table 16A provides exemplary targeting domains for correcting a mutation (e.g., G551D) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., G551D), have a high level of orthogonality and start with a 5'G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break

(Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 16A

258

5535.1 Table 16B provides exemplary targeting domains for correcting a mutation (e.g., G551D) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., G551D) and have a high level of orthogonality. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 16B

259

5535.1 24

CFTR-G551D-

- CAAGGUGAAUAACUAAUUAU 20

25 475

CFTR-G551D-

- CCUGGGGUUUUAUGGCUAGU 20

26 481

Table 16C provides exemplary targeting domains for correcting a mutation (e.g., G551D) in the CFTR gene selected according to the third tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., G551D) and start with a 5'G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through

complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 16C

Table 16D provides exemplary targeting domains for correcting a mutation (e.g., G551D) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., G551D). It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 16D

260

5535.1 CFTR-G551D-

- U UAAGAACUAUAAAUAA 17

31 495

CFTR-G551D-

- UGGAAUUGAAAAAAUCC 17

32 492

CFTR-G551D-

- UUUCUAUUUUUGGUAAU 17

33 487

CFTR-G551D-

- CUCUAAUUUUCUAUUUU 17

34 486

CFTR-G551D-

- CAUU UAAGAACUAUAAAUAA 20

35 482

CFTR-G551D-

- AUUGCUUUAUAUUCUGUUUC 20

36 476

CFTR-G551D-

- UCCUGGGGUUUUAUGGCUAG 20

37 480

CFTR-G551D-

- AAUGUUCAAAAUUUCAACUG 20

38 470

CFTR-G551D-

- AAUUUUCUAUUUUUGGUAAU 20

39 473

CFTR-G551D-

+ AUUGUCUUUCUCUGCAAACU 20

40 483

CFTR-G551D-

- UCUGGAAUUGAAAAAAUCCU 20

41 478

CFTR-G551D-

- ACUCUCUAAUUUUCUAUUUU 20

42 472

Table 17A provides exemplary targeting domains for correcting a mutation (e.g., G551D) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., G551D), have a high level of orthogonality, start with a 5'G, and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 17A

261

5535.1 44

CFTR-G551D-

+ GUCACUUUUAGUAUGCUCAAU 21

45 1899

CFTR-G551D-

+ GAGUCACUUUUAGUAUGCUCAAU 23

46 1900

CFTR-G551D-

- GGAGAAGGUGGAAUCACA 18

47 2160

CFTR-G551D-

- GUUCUUGGAGAAGGUGGAAUCACA 24

48 2161

CFTR-G551D-

- GCAAGAAUUUCUUUAGCAAG 20

49 746

CFTR-G551D-

- GAG CAAGAAU U U CU UUAGCAAG 22

50 1902

CFTR-G551D-

- GACAAUAUAGUUCUUGGAGAAGG 23

51 2162

CFTR-G551D-

- GUUUUAUGGCUAGUGGGUU 19

52 1903

CFTR-G551D-

- GGUUUUAUGGCUAGUGGGUU 20

53 751

CFTR-G551D-

- GGGUUUUAUGGCUAGUGGGUU 21

54 1904

CFTR-G551D-

- GGGGUUUUAUGGCUAGUGGGUU 22

55 1905

Table 17B provides exemplary targeting domains for correcting a mutation (e.g., G551D) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., G551D), have a high level of orthogonality and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 17B

262

5535.1 CFTR-G551D-

+ AGGAUUUUUUCAAUU CCAG AAA 22

58 1908

CFTR-G551D-

+ CAGG AU U U U U U CAAU U CCAG AAA 23

59 1909

CFTR-G551D-

+ CCAGG AU U U U U U CAAU U CCAG AAA 24

60 1910

CFTR-G551D-

+ UGUCUGUAAUUUUUUUAC 18

61 1911

CFTR-G551D-

+ AUGUCUGUAAUUUUUUUAC 19

62 1912

CFTR-G551D-

+ AAUGUCUGUAAUUUUUUUAC 20

63 763

CFTR-G551D-

+ CCACUAGCCAUAAAACCC 18

64 1913

CFTR-G551D-

+ CCCACUAGCCAUAAAACCC 19

65 1914

CFTR-G551D-

+ ACCCACUAGCCAUAAAACCC 20

66 1915

CFTR-G551D-

+ AACCCACUAGCCAUAAAACCC 21

67 1916

CFTR-G551D-

+ UAACCCACUAGCCAUAAAACCC 22

68 1917

CFTR-G551D-

+ UUAACCCACUAGCCAUAAAACCC 23

69 1918

CFTR-G551D-

+ CUUAACCCACUAGCCAUAAAACCC 24

70 1919

CFTR-G551D-

+ ACUUUUAGUAUGCUCAAU 18

71 1920

CFTR-G551D-

+ CACUUUUAGUAUGCUCAAU 19

72 1921

CFTR-G551D-

+ UCACUUUUAGUAUGCUCAAU 20

73 756

CFTR-G551D-

+ AGUCACUUUUAGUAUGCUCAAU 22

74 1922

CFTR-G551D-

+ AGAGUCACUUUUAGUAUGCUCAAU 24

75 1923

CFTR-G551D-

- UGGAGAAGGUGGAAUCACA 19

76 2163

CFTR-G551D-

- UUGGAGAAGGUGGAAUCACA 20

77 742

CFTR-G551D-

- CUUGGAGAAGGUGGAAUCACA 21

78 2164

CFTR-G551D- - UCUUGGAGAAGGUGGAAUCACA 22 2165

263

5535.1 79

CFTR-G551D-

- UUCUUGGAGAAGGUGGAAUCACA 23

80 2166

CFTR-G551D-

- CCUGGGGUUUUAUGGCUA 18

81 1924

CFTR-G551D-

- UCCUGGGGUUUUAUGGCUA 19

82 1925

CFTR-G551D-

- AUCCUGGGGUUUUAUGGCUA 20

83 750

CFTR-G551D-

- AAUCCUGGGGUUUUAUGGCUA 21

84 1926

CFTR-G551D-

- AAAUCCUGGGGUUUUAUGGCUA 22

85 1927

CFTR-G551D-

- AAAAUCCUGGGGUUUUAUGGCUA 23

86 1928

CFTR-G551D-

- AAAAAUCCUGGGGUUUUAUGGCUA 24

87 1929

CFTR-G551D-

- UGCUUUAUAUUCUGUUUC 18

88 1931

CFTR-G551D-

- UUGCUUUAUAUUCUGUUUC 19

89 1932

CFTR-G551D-

- AUUGCUUUAUAUUCUGUUUC 20

36 476

CFTR-G551D-

- UAUUGCUUUAUAUUCUGUUUC 21

90 1933

CFTR-G551D-

- CUAUUGCUUUAUAUUCUGUUUC 22

91 1934

CFTR-G551D-

- UCUAUUGCUUUAUAUUCUGUUUC 23

92 1935

CFTR-G551D-

- CUCUAUUGCUUUAUAUUCUGUUUC 24

93 1936

CFTR-G551D-

- AAGAAUUUCUUUAGCAAG 18

94 1937

CFTR-G551D-

- CAAGAAUUUCUUUAGCAAG 19

95 1938

CFTR-G551D-

- AGCAAGAAUUUCUUUAGCAAG 21

96 1939

CFTR-G551D-

- CG AGCAAG AAU U U CU U U AGCAAG 23

97 1940

CFTR-G551D-

- ACG AGCAAG AAU U U CU U U AG CAAG 24

98 1941

CFTR-G551D-

- UAUAGUUCUUGGAGAAGG 18

99 2167

264

5535.1 CFTR-G551D-

- AUAUAGUUCUUGGAGAAGG 19

100 2168

CFTR-G551D-

- AAUAUAGUUCUUGGAGAAGG 20

23 474

CFTR-G551D-

- CAAUAUAGUUCUUGGAGAAGG 21

101 2169

CFTR-G551D-

- ACAAUAUAGUUCUUGGAGAAGG 22

102 2170

CFTR-G551D-

- AGACAAUAUAGUUCUUGGAGAAGG 24

103 2171

CFTR-G551D-

- UUUUAUGGCUAGUGGGUU 18

104 1942

CFTR-G551D-

- UGGGGUUUUAUGGCUAGUGGGUU 23

105 1943

CFTR-G551D-

- CUGGGGUUUUAUGGCUAGUGGGUU 24

106 1944

Table 17C provides exemplary targeting domains for correcting a mutation (e.g., G551D) in the CFTR gene selected according to the third tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., G551D), start with a 5'G and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 17C

Table 17D provides exemplary targeting domains for correcting a mutation (e.g

G551D) in the CFTR gene selected according to the fourth tier parameters. The targetin

265

5535.1 domains bind within 200 bp from a mutation (e.g., G551D), and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 17D

266

5535.1 CFTR-G551D-

- CUGAGUGGAGAUCAACGAGC 20

126 2174

CFTR-G551D-

- ACUGAGUGGAGAUCAACGAGC 21

127 2175

CFTR-G551D-

- CACUGAGUGGAGAUCAACGAGC 22

128 2176

CFTR-G551D-

- ACACUGAGUGGAGAUCAACGAGC 23

129 2177

CFTR-G551D-

- CACACUGAGUGGAGAUCAACGAGC 24

130 2178

Table 17E provides exemplary targeting domains for correcting a mutation (e.g., G551D) in the CFTR gene selected according to the fifth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., G551D), and PAM is NNGRRV. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through

complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 17E

267

5535.1 139

CFTR-G551D-

+ AGAAACAGAAUAUAAAGCAA 20

140 765

CFTR-G551D-

+ C AG A A AC AG A A U A U A A AG C A A 21

141 1986

CFTR-G551D-

+ C C AG A A AC AG A A U A U A A AG C A A 22

142 1987

CFTR-G551D-

+ UCCAGAAACAGAAUAUAAAGCAA 23

143 1988

CFTR-G551D-

+ UUCCAGAAACAGAAUAUAAAGCAA 24

144 1989

CFTR-G551D-

+ ACAGAAUAUAAAGCAAUA 18

145 1997

CFTR-G551D-

+ A AC AG A A U A U A A AG C A A U A 19

146 1998

CFTR-G551D-

+ AAACAGAAUAUAAAGCAAUA 20

147 764

CFTR-G551D-

+ G A A AC AG A A U A U A A AG C A A U A 21

148 1999

CFTR-G551D-

+ AG A A AC AG A A U A U A A AG C A A U A 22

149 2000

CFTR-G551D-

+ C AG A A AC AG A A U A U A A AG C A A U A 23

150 2001

CFTR-G551D-

+ CCAGAAACAGAAUAUAAAGCAAUA 24

151 2002

CFTR-G551D-

+ UAGUUAUUCACCUUGCUA 18

152 2003

CFTR-G551D-

+ UUAGUUAUUCACCUUGCUA 19

153 2004

CFTR-G551D-

+ AUUAGUUAUUCACCUUGCUA 20

154 762

CFTR-G551D-

+ AAUUAGUUAUUCACCUUGCUA 21

155 2005

CFTR-G551D-

+ UAAUUAGUUAUUCACCUUGCUA 22

156 2006

CFTR-G551D-

+ AUAAUUAGUUAUUCACCUUGCUA 23

157 2007

CFTR-G551D-

+ AAUAAUUAGUUAUUCACCUUGCUA 24

158 2008

CFTR-G551D-

+ UUGUCUUUCUCUGCAAAC 18

159 2009

CFTR-G551D-

+ AUUGUCUUUCUCUGCAAAC 19

160 2010

268

5535.1 CFTR-G551D-

+ UAUUGUCUUUCUCUGCAAAC 20

161 760

CFTR-G551D-

+ AUAUUGUCUUUCUCUGCAAAC 21

162 2011

CFTR-G551D-

+ UAUAUUGUCUUUCUCUGCAAAC 22

163 2012

CFTR-G551D-

+ CUAUAUUGUCUUUCUCUGCAAAC 23

164 2013

CFTR-G551D-

+ ACUAUAUUGUCUUUCUCUGCAAAC 24

165 2014

CFTR-G551D-

+ UGUGAUUCCACCUUCUCC 18

166 2179

CFTR-G551D-

+ GUGUGAUUCCACCUUCUCC 19

167 2180

CFTR-G551D-

+ AGUGUGAUUCCACCUUCUCC 20

168 761

CFTR-G551D-

+ CAGUGUGAUUCCACCUUCUCC 21

169 2181

CFTR-G551D-

+ UCAGUGUGAUUCCACCUUCUCC 22

170 2182

CFTR-G551D-

+ CUCAGUGUGAUUCCACCUUCUCC 23

171 2183

CFTR-G551D-

+ ACUCAGUGUGAUUCCACCUUCUCC 24

172 2184

CFTR-G551D-

+ CCAGGAUUUUUUCAAUUC 18

173 2015

CFTR-G551D-

+ CCCAGGAUUUUUUCAAUUC 19

174 2016

CFTR-G551D-

+ CCCCAGG AU U U U U U CAAU U C 20

175 767

CFTR-G551D-

+ ACCCCAGGAUUUUUUCAAUUC 21

176 2017

CFTR-G551D-

+ AACCCCAGGAUUUUUUCAAUUC 22

177 2018

CFTR-G551D-

+ AAACCCCAGGAUUUUUUCAAUUC 23

178 2019

CFTR-G551D-

+ AAAACCCCAGG AU UUUUUCAAUUC 24

179 2020

CFTR-G551D-

+ CUAUUGCUUUAACCACAG 18

180 2021

CFTR-G551D-

+ ACUAUUGCUUUAACCACAG 19

181 2022

CFTR-G551D- + CACUAUUGCUUUAACCACAG 20 754

269

5535.1 182

CFTR-G551D-

+ ACACUAUUGCUUUAACCACAG 21

183 2023

CFTR-G551D-

+ CACACUAUUGCUUUAACCACAG 22

184 2024

CFTR-G551D-

+ U CACACU AU UG CU U U AACCACAG 23

185 2025

CFTR-G551D-

+ AUCACACUAUUGCUUUAACCACAG 24

186 2026

CFTR-G551D-

+ U U ACCAAAAAU AGAAAAU 18

187 2027

CFTR-G551D-

+ AU U ACCAAAAAU AG AAAAU 19

188 2028

CFTR-G551D-

+ U AU U ACCAAAAAU AG AAAAU 20

189 758

CFTR-G551D-

+ CUAUU ACCAAAAAU AG AAAAU 21

190 2029

CFTR-G551D-

+ CCU AUU ACCAAAAAU AG AAAAU 22

191 2030

CFTR-G551D-

+ U CCU AU U ACCAAAAAU AG AAAAU 23

192 2031

CFTR-G551D-

+ G U CCU AU U ACCAAAAAU AG AAAAU 24

193 2032

CFTR-G551D-

+ AGUAUGCUCAAUCUGAAU 18

194 2033

CFTR-G551D-

+ UAGUAUGCUCAAUCUGAAU 19

195 2034

CFTR-G551D-

+ UUAGUAUGCUCAAUCUGAAU 20

196 755

CFTR-G551D-

+ UUUAGUAUGCUCAAUCUGAAU 21

197 2035

CFTR-G551D-

+ UUUUAGUAUGCUCAAUCUGAAU 22

198 2036

CFTR-G551D-

+ CUUUUAGUAUGCUCAAUCUGAAU 23

199 2037

CFTR-G551D-

+ ACUUUUAGUAUGCUCAAUCUGAAU 24

200 2038

CFTR-G551D-

+ UGUCUUUCUCUGCAAACU 18

201 2039

CFTR-G551D-

+ UUGUCUUUCUCUGCAAACU 19

202 2040

CFTR-G551D-

+ AUUGUCUUUCUCUGCAAACU 20

40 483

270

5535.1 CFTR-G551D-

+ UAUUGUCUUUCUCUGCAAACU 21

203 2041

CFTR-G551D-

+ AUAUUGUCUUUCUCUGCAAACU 22

204 2042

CFTR-G551D-

+ UAUAUUGUCUUUCUCUGCAAACU 23

205 2043

CFTR-G551D-

+ CUAUAUUGUCUUUCUCUGCAAACU 24

206 2044

CFTR-G551D-

+ U U AACCACAG UUGAAAU U 18

207 2045

CFTR-G551D-

+ UUUAACCACAGU U G AAA U U 19

208 2046

CFTR-G551D-

+ CU U U AACCACAG UUGAAAU U 20

209 753

CFTR-G551D-

+ GCUUU AACCACAG UUGAAAU U 21

210 2047

CFTR-G551D-

+ UGCUUUAACCACAGUUGAAAUU 22

211 2048

CFTR-G551D-

+ U UG CU U U AACCACAG UUGAAAU U 23

212 2049

CFTR-G551D-

+ AUUGCUUUAACCACAGUUGAAAUU 24

213 2050

CFTR-G551D-

- UAUAUUCUGUUUCUGGAA 18

214 2051

CFTR-G551D-

- UUAUAUUCUGUUUCUGGAA 19

215 2052

CFTR-G551D-

- UUUAUAUUCUGUUUCUGGAA 20

216 748

CFTR-G551D-

- CUUUAUAUUCUGUUUCUGGAA 21

217 2053

CFTR-G551D-

- GCUUUAUAUUCUGUUUCUGGAA 22

218 2054

CFTR-G551D-

- UGCUUUAUAUUCUGUUUCUGGAA 23

219 2055

CFTR-G551D-

- UUGCUUUAUAUUCUGUUUCUGGAA 24

220 2056

CFTR-G551D-

- AUUUUCUAUUUUUGGUAA 18

221 2059

CFTR-G551D-

- AAUUUUCUAUUUUUGGUAA 19

222 2060

CFTR-G551D-

- UAAUUUUCUAUUUUUGGUAA 20

223 736

CFTR-G551D- - CUAAUUUUCUAUUUUUGGUAA 21 2061

271

5535.1 224

CFTR-G551D-

- UCUAAUUUUCUAUUUU UGGUAA 22

225 2062

CFTR-G551D-

- CUCUAAUUUUCUAUUU UUGGUAA 23

226 2063

CFTR-G551D-

- UCUCUAAUUU UCUAUU UUUGGUAA 24

227 2064

CFTR-G551D-

- GACAUCUCCAAGU UUGCA 18

228 2065

CFTR-G551D-

- GGACAUCUCCAAGUUUGCA 19

229 2066

CFTR-G551D-

- AGGACAUCUCCAAGU UUGCA 20

230 738

CFTR-G551D-

- UAGGACAUCUCCAAGUUUGCA 21

231 2067

CFTR-G551D-

- AUAGGACAUCUCCAAGUUUGCA 22

232 2068

CFTR-G551D-

- AAUAGGACAUCUCCAAGUUUGCA 23

233 2069

CFTR-G551D-

- UAAUAGGACAUCUCCAAGUUUGCA 24

234 2070

CFTR-G551D-

- CACACU G AG UGG AG AU CA 18

235 2185

CFTR-G551D-

- UCACACUGAGUGGAGAUCA 19

236 2186

CFTR-G551D-

- AUCACACUGAGUGGAGAUCA 20

237 2187

CFTR-G551D-

- AAUCACACUGAGUGGAGAUCA 21

238 2188

CFTR-G551D-

- GAAUCACACUGAGUGGAGAUCA 22

239 2189

CFTR-G551D-

- GGAAUCACACUGAGUGGAGAUCA 23

240 2190

CFTR-G551D-

- UGGAAUCACACUGAGUGGAGAUCA 24

241 2191

CFTR-G551D-

- GUGCCUUUCAAAUUCAGA 18

242 2077

CFTR-G551D-

- UGUGCCUU UCAAAUUCAGA 19

243 2078

CFTR-G551D-

- AUGUGCCUUUCAAAUUCAGA 20

244 735

CFTR-G551D-

- GAUGUGCCUUUCAAAUUCAGA 21

245 2079

272

5535.1 CFTR-G551D-

- AGAUGUGCCUUUCAAAUUCAGA 22

246 2080

CFTR-G551D-

- AAGAUGUGCCUUUCAAAUUCAGA 23

247 2081

CFTR-G551D-

- GAAGAUGUGCCUUUCAAAUUCAGA 24

248 2082

CFTR-G551D-

- AUAUAUGAUUACAUUAGA 18

249 2083

CFTR-G551D-

- GAUAUAUGAUUACAUUAGA 19

250 2084

CFTR-G551D-

- UGAUAUAUGAUUACAU UAGA 20

20 471

CFTR-G551D-

- GUGAUAUAUGAUUACAUUAGA 21

251 2085

CFTR-G551D-

- UGUGAUAUAUGAUUACAUUAGA 22

252 2086

CFTR-G551D-

- GUGUGAUAUAUGAUUACAUUAGA 23

253 2087

CFTR-G551D-

- AGUGUGAUAUAUGAUUACAUUAGA 24

254 2088

CFTR-G551D-

- AAGGUGGAAUCACACUGA 18

255 2089

CFTR-G551D-

- GAAGGUGGAAUCACACUGA 19

256 2090

CFTR-G551D-

- AGAAGGUGGAAUCACACUGA 20

257 743

CFTR-G551D-

- GAGAAGGUGGAAUCACACUGA 21

258 2091

CFTR-G551D-

- GGAGAAGGUGGAAUCACACUGA 22

259 2192

CFTR-G551D-

- UGGAGAAGGUGGAAUCACACUGA 23

260 2193

CFTR-G551D-

- UUGGAGAAGGUGGAAUCACACUGA 24

261 2194

CFTR-G551D-

- UCUGGAAUUGAAAAAAUC 18

262 2098

CFTR-G551D-

- UUCUGGAAUUGAAAAAAUC 19

263 2099

CFTR-G551D-

- UU UCUGGAAUUGAAAAAAUC 20

264 749

CFTR-G551D-

- GUUUCUGGAAUUGAAAAAAUC 21

265 2100

CFTR-G551D- - UGUUUCUGGAAUUGAAAAAAUC 22 2101

273

5535.1 266

CFTR-G551D-

- CUGUUUCUGGAAUUGAAAAAAUC 23

267 2102

CFTR-G551D-

- UCUGUUUCUGGAAUUGAAAAAAUC 24

268 2103

CFTR-G551D-

- AGAAAGACAAUAUAGUUC 18

269 2195

CFTR-G551D-

- GAGAAAGACAAUAUAGUUC 19

270 2196

CFTR-G551D-

- AGAGAAAGACAAUAUAGUUC 20

271 739

CFTR-G551D-

- CAG AG AAAG ACAAU AU AG U U C 21

272 2197

CFTR-G551D-

- GCAGAGAAAGACAAUAUAGUUC 22

273 2198

CFTR-G551D-

- UGCAGAGAAAGACAAUAUAGUUC 23

274 2199

CFTR-G551D-

- UUGCAGAGAAAGACAAUAUAGUUC 24

275 2200

CFTR-G551D-

- AUAUAGUUCUUGGAGAAG 18

276 2201

CFTR-G551D-

- AAUAUAGUUCUUGGAGAAG 19

277 2202

CFTR-G551D-

- CAAUAUAGUUCUUGGAGAAG 20

278 741

CFTR-G551D-

- ACAAUAUAGUUCUUGGAGAAG 21

279 2203

CFTR-G551D-

- GACAAUAUAGUUCUUGGAGAAG 22

280 2204

CFTR-G551D-

- AGACAAUAUAGUUCUUGGAGAAG 23

281 2205

CFTR-G551D-

- AAG ACAAU AU AG U U CU U GG AG AAG 24

282 2206

CFTR-G551D-

- AGGUGGAAUCACACUGAG 18

283 2111

CFTR-G551D-

- AAGGUGGAAUCACACUGAG 19

284 2112

CFTR-G551D-

- GAAGGUGGAAUCACACUGAG 20

8 461

CFTR-G551D-

- AGAAGGUGGAAUCACACUGAG 21

285 2113

CFTR-G551D-

- GAGAAGGUGGAAUCACACUGAG 22

286 2114

274

5535.1 CFTR-G551D-

- GGAGAAGGUGGAAUCACACUGAG 23

287 2207

CFTR-G551D-

- UGGAGAAGGUGGAAUCACACUGAG 24

288 2208

CFTR-G551D-

- GAUAUAUGAUUACAUUAG 18

289 2117

CFTR-G551D-

- UGAUAUAUGAUUACAUUAG 19

290 2118

CFTR-G551D-

- GUGAUAUAUGAUUACAUUAG 20

291 734

CFTR-G551D-

- UGUGAUAUAUGAUUACAUUAG 21

292 2119

CFTR-G551D-

- GUGUGAUAUAUGAUUACAUUAG 22

293 2120

CFTR-G551D-

- AGUGUGAUAUAUGAUUACAUUAG 23

294 2121

CFTR-G551D-

- UAGUGUGAUAUAUGAUUACAUUAG 24

295 2122

CFTR-G551D-

- AAGACAAUAUAGUUCUUG 18

296 2209

CFTR-G551D-

- AAAGACAAUAUAGUUCUUG 19

297 2210

CFTR-G551D-

- GAAAGACAAUAUAGUUCUUG 20

298 740

CFTR-G551D-

- AGAAAGACAAUAUAGUUCUUG 21

299 2211

CFTR-G551D-

- GAGAAAGACAAUAUAGUUCUUG 22

300 2212

CFTR-G551D-

- AG AG AAAG ACAAU AU AG U U CU UG 23

301 2213

CFTR-G551D-

- CAG AG AAAG ACAAU AU AG U U CU UG 24

302 2214

CFTR-G551D-

- AGGACAUCUCCAAGUUUG 18

303 2123

CFTR-G551D-

- UAGGACAUCUCCAAGUUUG 19

304 2124

CFTR-G551D-

- AUAGGACAUCUCCAAGUUUG 20

305 737

CFTR-G551D-

- AAUAGGACAUCUCCAAGUUUG 21

306 2125

CFTR-G551D-

- UAAUAGGACAUCUCCAAGUUUG 22

307 2126

CFTR-G551D- - GUAAUAGGACAUCUCCAAGUUUG 23 2127

275

5535.1 308

CFTR-G551D-

- GGUAAUAGGACAUCUCCAAGUUUG 24

309 2128

CFTR-G551D-

- UGUGAUAUAUGAUUACAU 18

310 2129

CFTR-G551D-

- GUGUGAUAUAUGAUUACAU 19

311 2130

CFTR-G551D-

- AGUGUGAUAUAUGAUUACAU 20

312 733

CFTR-G551D-

- UAGUGUGAUAUAUGAUUACAU 21

313 2131

CFTR-G551D-

- AUAGUGUGAUAUAUGAUUACAU 22

314 2132

CFTR-G551D-

- AAUAGUGUGAUAUAUGAUUACAU 23

315 2133

CFTR-G551D-

- CAAUAGUGUGAUAUAUGAUUACAU 24

316 2134

CFTR-G551D-

- G AAAG ACAAU AU AG U U CU 18

317 2135

CFTR-G551D-

- AGAAAGACAAUAUAGUUCU 19

318 2136

CFTR-G551D-

- GAG AAAG ACAAU AU AG U U CU 20

9 453

CFTR-G551D-

- AGAGAAAGACAAUAUAGUUCU 21

319 2137

CFTR-G551D-

- CAG AG AAAG ACAAU AU AG U U CU 22

320 2138

CFTR-G551D-

- GCAGAGAAAGACAAUAUAGUUCU 23

321 2139

CFTR-G551D-

- UGCAGAGAAAGACAAUAUAGUUCU 24

322 2140

CFTR-G551D-

- GGGU U AAG AAU CACAU U U 18

323 2215

CFTR-G551D-

- UGGGUUAAGAAUCACAUUU 19

324 2216

CFTR-G551D-

- GUGGGUUAAGAAUCACAUUU 20

325 752

CFTR-G551D-

- AGUGGGUUAAGAAUCACAUUU 21

326 2217

CFTR-G551D-

- UAGUGGGUUAAGAAUCACAUUU 22

327 2218

CFTR-G551D-

- CUAGUGGGUUAAGAAUCACAUUU 23

328 2219

276

5535.1 CFTR-G551D-

- GCUAGUGGGUUAAGAAUCACAUUU 24

329 2220

CFTR-G551D-

- UUGCUUUAUAUUCUGUUU 18

330 2148

CFTR-G551D-

- AUUGCUUUAUAUUCUGUUU 19

331 2149

CFTR-G551D-

- UAUUGCUUUAUAUUCUGUUU 20

332 747

CFTR-G551D-

- CUAUUGCUUUAUAUUCUGUUU 21

333 2150

CFTR-G551D-

- UCUAUUGCUUUAUAUUCUGUUU 22

334 2151

CFTR-G551D-

- CUCUAUUGCUUUAUAUUCUGUUU 23

335 2152

CFTR-G551D-

- UCUCUAUUGCUUUAUAUUCUGUUU 24

336 2153

Table 18A provides exemplary targeting domains for correcting a mutation (e.g., G551D) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., G551D), have a high level of orthogonality and start with a 5'G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 18A

Table 18B provides exemplary targeting domains for correcting a mutation (e.g., G551D) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., G551D) and have a high level of orthogonality. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with

277

5535.1 a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 18B

Table 18C provides exemplary targeting domains for correcting a mutation (e.g.,

G551D) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., G551D). It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 18C

278

5535.1 CFTR-G551D-

- AAUUACAGACAUUUCUC 17

349 2158

CFTR-G551D-

+ CCAUUAUUUAUAGUUCUUAA 20

350 931

CFTR-G551D-

+ UGCUCGUUGAUCUCCACUCA 20

351 2222

CFTR-G551D-

- AAAAAUUACAGACAUUUCUC 20

352 2159

Table 19A provides exemplary targeting domains for correcting a mutation (e.g., N1303K) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., N1303K), have a high level of orthogonality and start with a 5'G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 19A

Table 19B provides exemplary targeting domains for correcting a mutation (e.g., N1303K) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., N1303K) and have a high level of

orthogonality. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the

279

5535.1 Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 19B

Table 19C provides exemplary targeting domains for correcting a mutation (e.g N1303K) in the CFTR gene selected according to the third tier parameters. The targetin domains bind within 200 bp from a mutation (e.g., N1303K) and start with a 5'G. It is

280

5535.1 contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 19C

Table 19D provides exemplary targeting domains for correcting a mutation (e.g., N1303K) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., N1303K). It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 19D

281

5535.1 31

CFTR-N 1303K-

- UAACUGAAAUGAUUUUGAAA 20

32 2254

CFTR-N 1303K-

- CUAACUGAAAUGAUUU UGAA 20

33 2255

CFTR-N 1303K-

- AAU AU U U U ACAAU ACAAU AA 20

34 2256

CFTR-N 1303K-

- UAAAAUUUGAGAGAACUUGA 20

35 2257

CFTR-N 1303K-

- AAAU AU U U U ACAAU ACAAU A 20

36 2258

CFTR-N 1303K-

- AUGGAGUACCCUAACAUACC 20

37 2259

CFTR-N 1303K-

- UAGAAAGUAUUUAUUUUUUC 20

38 2260

CFTR-N 1303K-

- AACUGAAAUGAUUUUGAAAG 20

39 2261

CFTR-N 1303K-

- AGUUGGAUCCCUAUGAACAG 20

40 2262

CFTR-N 1303K-

- UGGAACAUUUAG A A A A A AG U 20

41 2263

Table 20A provides exemplary targeting domains for correcting a mutation (e.g., N1303K) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., N1303K), have a high level of orthogonality, start with a 5'G, and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 20A

282

5535.1 CFTR-N1303K-

- GCUAACUGAAAUGAUU UUGAA 21

44 2266

CFTR-N1303K-

- GCUGCUAACUGAAAUGAUUUUGAA 24

45 2267

CFTR-N1303K-

- GAACUUGAUGGUAAGUAC 18

46 2268

CFTR-N1303K-

- GAGAACUUGAUGGUAAGUAC 20

47 2269

CFTR-N1303K-

- GAGAGAACUUGAUGGUAAGUAC 22

48 2270

Table 20B provides exemplary targeting domains for correcting a mutation (e.g., N1303K) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., N1303K), have a high level of orthogonality and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 20B

283

5535.1 56

CFTR-N 1303K-

- AGAACUUGAUGGUAAGUAC 19

57 2279

CFTR-N 1303K-

- AGAGAACUUGAUGGUAAGUAC 21

58 2280

CFTR-N 1303K-

- UGAGAGAACUUGAUGGUAAGUAC 23

59 2281

CFTR-N 1303K-

- UUGAGAGAACUUGAUGGUAAGUAC 24

60 2282

Table 20C provides exemplary targeting domains for correcting a mutation (e.g., N1303K) in the CFTR gene selected according to the third tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., N1303K), start with a 5'G and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 20C

Table 20D provides exemplary targeting domains for correcting a mutation (e.g., N1303K) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., N1303K), and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 20D

4th Tier

284

5535.1 Target Site gRNA Name DNA Strand Targeting Domain

Length Seq ID

CFTR-N1303K-

+ ACAUGCACACAAAGUGUG 18

65 2287

CFTR-N1303K-

+ U ACAU G CAC ACAAAG U G U G 19

66 2288

CFTR-N1303K-

+ AUACAUGCACACAAAGUGUG 20

67 2289

CFTR-N1303K-

+ CAUACAUGCACACAAAGUGUG 21

68 2290

CFTR-N1303K-

+ ACAUACAUGCACACAAAGUGUG 22

69 2291

CFTR-N1303K-

+ CACAUACAUGCACACAAAGUGUG 23

70 2292

CFTR-N1303K-

+ ACACAUACAUGCACACAAAGUGUG 24

71 2293

CFTR-N1303K-

+ AG AAAAG AAG AAG AAAG U 18

72 2294

CFTR-N1303K-

+ AAG AAAAG AAG AAG AAAG U 19

73 2295

CFTR-N1303K-

+ AAAG AAAAG AAG AAG AAAG U 20

74 2296

CFTR-N1303K-

+ AAAAG AAAAG AAG AAG AAAG U 21

75 2297

CFTR-N1303K-

+ AAAAAG AAAAG AAG AAG AAAG U 22

76 2298

CFTR-N1303K-

+ AAAAAAG AAAAG AAG AAG AAAG U 23

77 2299

CFTR-N1303K-

+ CAAAAAAG AAAAG AAG AAG AAAG U 24

78 2300

CFTR-N1303K-

+ UCAGCCAUUUGUGUUGGU 18

79 2301

CFTR-N1303K-

+ AUCAGCCAUUUGUGUUGGU 19

80 2302

CFTR-N1303K-

+ UAUCAGCCAUUUGUGU UGGU 20

81 2303

CFTR-N1303K-

+ AUAUCAGCCAUUUGUGUUGGU 21

82 2304

CFTR-N1303K-

+ UAUAUCAGCCAUU UGUGUUGGU 22

83 2305

CFTR-N1303K-

+ CUAUAUCAGCCAUUUGUGUUGGU 23

84 2306

CFTR-N1303K- - UGUGUGUGCACAACUUUAAAA 21 2307

285

5535.1 85

CFTR-N1303K-

- AUGUGUGUGCACAACU UUAAAA 22

86 2308

CFTR-N1303K-

- UAUGUGUGUGCACAACUUUAAAA 23

87 2309

CFTR-N1303K-

- AACUGAAAUGAUUUUGAA 18

88 2310

CFTR-N1303K-

- UAACUGAAAUGAUUUUGAA 19

89 2311

CFTR-N1303K-

- CUAACUGAAAUGAUUU UGAA 20

33 2255

CFTR-N1303K-

- UGGAACAUUUAGAAAAAAG 19

90 2312

CFTR-N1303K-

- CUGGAACAUUUAGAAAAAAG 20

91 2313

CFTR-N1303K-

- UCUGGAACAUUUAGAAAAAAG 21

92 2314

CFTR-N1303K-

- U U CUGG AACAU U U AG AAAAAAG 22

93 2315

CFTR-N1303K-

- UU UCUGGAACAUUUAGAAAAAAG 23

94 2316

CFTR-N1303K-

- U U U U CUGG AACAU U U AG AAAAAAG 24

95 2317

CFTR-N1303K-

- UUGGAUCCCUAUGAACAG 18

96 2318

CFTR-N1303K-

- AGUUGGAUCCCUAUGAACAG 20

40 2262

CFTR-N1303K-

- AAGUUGGAUCCCUAUGAACAG 21

97 2319

CFTR-N1303K-

- AAAGUUGGAUCCCUAUGAACAG 22

98 2320

CFTR-N1303K-

- AAAAGUUGGAUCCCUAUGAACAG 23

99 2321

CFTR-N1303K-

- AAAAAGUUGGAUCCCUAUGAACAG 24

100 2322

Table 20E provides exemplary targeting domains for correcting a mutation (e.g., N1303K) in the CFTR gene selected according to the fifth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., N1303K), and PAM is NNGRRV. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with

286

5535.1 a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 20E

287

5535.1 CFTR-

+ UUCUUGAUCACUCCACUGUUCA 22

N1303K-119 2341

CFTR-

+ UUUCUUGAUCACUCCACUGUUCA 23

N1303K-120 2342

CFTR-

+ AUUUCUUGAUCACUCCACUGUUCA 24

N1303K-121 2343

CFTR-

+ ACUUUUUUCUAAAUGUUC 18

N1303K-122 2344

CFTR-

+ AACUUUUUUCUAAAUGUUC 19

N1303K-123 2345

CFTR-

+ CAACUUUUUUCUAAAUGUUC 20

N1303K-124 2346

CFTR-

+ CCAACUUUUUUCUAAAUGUUC 21

N1303K-125 2347

CFTR-

+ UCCAACUUUUUUCUAAAUGUUC 22

N1303K-126 2348

CFTR-

+ AUCCAACUUUUUUCUAAAUGUUC 23

N1303K-127 2349

CFTR-

+ GAUCCAACUUUUUUCUAAAUGUUC 24

N1303K-128 2350

CFTR-

+ U A U AG C A A A A A AG A A A AG 18

N1303K-129 2351

CFTR-

+ C U A U AG C A A A A A AG A A A AG 19

N1303K-130 2352

CFTR-

+ U C U A U AG C A A A A A AG A A A AG 20

N1303K-131 2353

CFTR-

+ UUCUAUAG C A A A A A AG A A A AG 21

N1303K-132 2354

CFTR-

+ UUUCUAUAG C A A A A A AG A A A AG 22

N1303K-133 2355

CFTR-

+ CUUUCUAUAG C A A A A A AG A A A AG 23

N1303K-134 2356

CFTR-

+ ACUUUCUAUAGCAAAAAAGAAAAG 24

N1303K-135 2357

CFTR-

+ AU UG U AAAAU AU U U CAAG 18

N1303K-136 2358

CFTR-

+ U AU UG U AAAAU AU U U CAAG 19

N1303K-137 2359

CFTR-

+ GUAUUGUAAAAUAUUUCAAG 20

N1303K-138 2360

CFTR-

+ UGUAUUGUAAAAUAUUUCAAG 21

N1303K-139 2361

CFTR- + UUGUAUUGUAAAAUAUUUCAAG 22 2362

288

5535.1 N1303K-140

CFTR-

+ AUUGUAUUGUAAAAUAUUUCAAG 23

N1303K-141 2363

CFTR-

+ UAUUGUAUUGUAAAAUAUUUCAAG 24

N1303K-142 2364

CFTR-

+ AGCAAAAAAGAAAAGAAG 18

N1303K-143 2365

CFTR-

+ U AG C A A A A A AG A A A AG AAG 19

N1303K-144 2366

CFTR-

+ AU AGCAAAAAAGAAAAGAAG 20

N1303K-145 2367

CFTR-

+ UAU AGCAAAAAAGAAAAGAAG 21

N1303K-146 2368

CFTR-

+ C U A U AG C A A A A A AG A A A AG A AG 22

N1303K-147 2369

CFTR-

+ UCUAU AGCAAAAAAGAAAAGAAG 23

N1303K-148 2370

CFTR-

+ UUCUAUAGCAAAAAAGAAAAGAAG 24

N1303K-149 2371

CFTR-

+ G AAAAAU U AU U U U AAAAU 18

N1303K-150 2372

CFTR-

+ AG AAAAAU U AU U U U AAAAU 19

N1303K-151 2373

CFTR-

+ U AG AAAAAU U AU U U U AAAAU 20

N1303K-152 2374

CFTR-

+ G U AG AAAAAU U AU U U U AAAAU 21

N1303K-153 2375

CFTR-

+ AG U AG AAAAAU U AU U U U AAAAU 22

N1303K-154 2376

CFTR-

+ AAG U AG AAAAAU U AU U U U AAAAU 23

N1303K-155 2377

CFTR-

+ CAAG U AG AAAAAU U AU U U U AAAAU 24

N1303K-156 2378

CFTR-

- UGUGUGCACAACUUUAAA 18

N1303K-157 2379

CFTR-

- GUGUGUGCACAACUUUAAA 19

N1303K-158 2380

CFTR-

- UGUGUGUGCACAACUUUAAA 20

N1303K-159 2381

CFTR-

- AUGUGUGUGCACAACUUUAAA 21

N1303K-160 2382

CFTR-

- UAUGUGUGUGCACAACUUUAAA 22

N1303K-161 2383

289

5535.1 CFTR-

- GUAUGUGUGUGCACAACUUUAAA 23

N1303K-162 2384

CFTR-

- UGUAUGUGUGUGCACAACUUUAAA 24

N 1303K-163 2385

CFTR-

- U AU U U U ACAAU ACAAU AA 18

N 1303K-164 2386

CFTR-

- AU AU U U U ACAAU ACAAU AA 19

N 1303K-165 2387

CFTR-

- AAU AU U U U ACAAU ACAAU AA 20

N 1303K-34 2256

CFTR-

- AAAU AU U U U ACAAU ACAAU AA 21

N 1303K-166 2388

CFTR-

- G AAAU AU U U U ACAAU ACAAU AA 22

N 1303K-167 2389

CFTR-

- UG AAAU AU U U U ACAAU ACAAU AA 23

N 1303K-168 2390

CFTR-

- U U G AAAU AU U U U ACAAU ACAAU AA 24

N 1303K-169 2391

CFTR-

- AUGAGGUAAGGCUGCUAA 18

N 1303K-170 2392

CFTR-

- GAUGAGGUAAGGCUGCUAA 19

N 1303K-171 2393

CFTR-

- AGAUGAGGUAAGGCUGCUAA 20

N 1303K-172 2394

CFTR-

- CAGAUGAGGUAAGGCUGCUAA 21

N 1303K-173 2395

CFTR-

- GCAGAUGAGGUAAGGCUGCUAA 22

N 1303K-174 2396

CFTR-

- UGCAGAUGAGGUAAGGCUGCUAA 23

N 1303K-175 2397

CFTR-

- UUGCAGAUGAGGUAAGGCUGCUAA 24

N 1303K-176 2398

CFTR-

- GU UGGAUCCCUAUGAACA 18

N 1303K-177 2399

CFTR-

- AGUUGGAUCCCUAUGAACA 19

N 1303K-178 2400

CFTR-

- AAGUUGGAUCCCUAUGAACA 20

N 1303K-179 2401

CFTR-

- AAAGUUGGAUCCCUAUGAACA 21

N 1303K-180 2402

CFTR-

- AAAAGUUGGAUCCCUAUGAACA 22

N 1303K-181 2403

CFTR- - AAAAAGUUGGAUCCCUAUGAACA 23 2404

290

5535.1 N1303K-182

CFTR-

- AAAAAAGUUGGAUCCCUAUGAACA 24

N1303K-183 2405

CFTR-

- U AAAAU AU U AAAAU U UG A 18

N1303K-184 2406

CFTR-

- AU AAAAU AUU AAAAU UUGA 19

N1303K-185 2407

CFTR-

- GAU AAAAU AUU AAAAU UUGA 20

N1303K-186 2408

CFTR-

- UG AU AAAAU AU U AAAAU UUGA 21

N1303K-187 2409

CFTR-

- AUGAUAAAAUAUUAAAAUUUGA 22

N1303K-188 2410

CFTR-

- CAU GAU AAAAU AU U AAAAU UUGA 23

N1303K-189 2411

CFTR-

- ACAUG AU AAAAU AU U AAAAU UUGA 24

N1303K-190 2412

CFTR-

- UAACUGAAAUGAUUUUGA 18

N1303K-191 2413

CFTR-

- CUAACUGAAAUGAUUUUGA 19

N1303K-192 2414

CFTR-

- GCUAACUGAAAUGAUUUUGA 20

N1303K-193 2415

CFTR-

- UGCUAACUGAAAUGAUUUUGA 21

N1303K-194 2416

CFTR-

- CUGCUAACUGAAAUGAUUUUGA 22

N1303K-195 2417

CFTR-

- GCUGCUAACUGAAAUGAUUUUGA 23

N1303K-196 2418

CFTR-

- GGCUGCUAACUGAAAUGAUUUUGA 24

N1303K-197 2419

CFTR-

- UGGAGUGAUCAAGAAAUA 18

N1303K-198 2420

CFTR-

- GUGGAGUGAUCAAGAAAUA 19

N1303K-199 2421

CFTR-

- AGUGGAGUGAUCAAGAAAUA 20

N1303K-18 2240

CFTR-

- CAGUGGAGUGAUCAAGAAAUA 21

N1303K-200 2422

CFTR-

- ACAGUGGAGUGAUCAAGAAAUA 22

N1303K-201 2423

CFTR-

- AACAGUGGAGUGAUCAAGAAAUA 23

N1303K-202 2424

291

5535.1 CFTR-

- GAACAGUGGAGUGAUCAAGAAAUA 24

N1303K-203 2425

CFTR-

- AUAUUUUACAAUACAAUA 18

N1303K-204 2426

CFTR-

- AAU AU U U U ACAAU ACAAU A 19

N1303K-205 2427

CFTR-

- AAAUAU U U U ACAAU ACAAU A 20

N1303K-36 2258

CFTR-

- G AAAU AU U U U ACAAU ACAAU A 21

N1303K-206 2428

CFTR-

- UG AAAUAU U U U ACAAU ACAAU A 22

N1303K-207 2429

CFTR-

- U UG AAAU AU U U U ACAAU ACAAU A 23

N1303K-208 2430

CFTR-

- CUUGAAAUAUUUUACAAUACAAUA 24

N1303K-209 2431

CFTR-

- UUCUUUUCUUUUUUGCUA 18

N1303K-210 2432

CFTR-

- CUUCUUUUCUUUUUUGCUA 19

N1303K-211 2433

CFTR-

- UCUUCUUUUCUUUUUUGCUA 20

N1303K-212 2434

CFTR-

- UUCUUCUUUUCUUUUUUGCUA 21

N1303K-213 2435

CFTR-

- CUUCUUCUUUUCUUUUUUGCUA 22

N1303K-214 2436

CFTR-

- UCUUCUUCUUUUCUUUUUUGCUA 23

N1303K-215 2437

CFTR-

- UUCUUCUUCUUUUCUUUUUUGCUA 24

N1303K-216 2438

CFTR-

- UGGAGUACCCUAACAUAC 18

N1303K-217 2439

CFTR-

- AUGGAGUACCCUAACAUAC 19

N1303K-218 2440

CFTR-

- AAUGGAGUACCCUAACAUAC 20

N1303K-219 2441

CFTR-

- AAAUGGAGUACCCUAACAUAC 21

N1303K-220 2442

CFTR-

- AAAAUGGAGUACCCUAACAUAC 22

N1303K-221 2443

CFTR-

- UAAAAUGGAGUACCCUAACAUAC 23

N1303K-222 2444

CFTR- - UUAAAAUGGAGUACCCUAACAUAC 24 2445

292

5535.1 N1303K-223

CFTR-

- UUAAAAUAAUUUUUCUAC 18

N1303K-224 2446

CFTR-

- U U UAAAAUAAU U U U U CU AC 19

N1303K-225 2447

CFTR-

- U U U UAAAAUAAU U U U U CU AC 20

N1303K-226 2448

CFTR-

- AU U U UAAAAUAAU U U U U CU AC 21

N1303K-227 2449

CFTR-

- UAUUUUAAAAUAAUUUUUCUAC 22

N1303K-228 2450

CFTR-

- UUAUUUUAAAAUAAUUUUUCUAC 23

N1303K-229 2451

CFTR-

- CUUAUUUUAAAAUAAUUUUUCUAC 24

N1303K-230 2452

CFTR-

- GGAGUACCCUAACAUACC 18

N1303K-231 2453

CFTR-

- UGGAGUACCCUAACAUACC 19

N1303K-232 2454

CFTR-

- AUGGAGUACCCUAACAUACC 20

N1303K-37 2259

CFTR-

- AAUGGAGUACCCUAACAUACC 21

N1303K-233 2455

CFTR-

- AAAUGGAGUACCCUAACAUACC 22

N1303K-234 2456

CFTR-

- AAAAUGGAGUACCCUAACAUACC 23

N1303K-235 2457

CFTR-

- UAAAAUGGAGUACCCUAACAUACC 24

N1303K-236 2458

CFTR-

- AUGAACAGUGGAGUGAUC 18

N1303K-237 2459

CFTR-

- UAUGAACAGUGGAGUGAUC 19

N1303K-238 2460

CFTR-

- CUAUGAACAGUGGAGUGAUC 20

N1303K-239 2461

CFTR-

- CCUAUGAACAGUGGAGUGAUC 21

N1303K-240 2462

CFTR-

- CCCUAUGAACAGUGGAGUGAUC 22

N1303K-241 2463

CFTR-

- UCCCUAUGAACAGUGGAGUGAUC 23

N1303K-242 2464

CFTR-

- AUCCCUAUGAACAGUGGAGUGAUC 24

N1303K-243 2465

293

5535.1 CFTR-

- GAAAGUAUUUAUUUUUUC 18

N1303K-244 2466

CFTR-

- AGAAAGUAUUUAUUUUUUC 19

N 1303K-245 2467

CFTR-

- UAGAAAGUAUUUAUUUUUUC 20

N 1303K-38 2260

CFTR-

- AUAGAAAGUAUUUAUUUUUUC 21

N 1303K-246 2468

CFTR-

- UAUAGAAAGUAUUUAUUUUUUC 22

N 1303K-247 2469

CFTR-

- CUAUAGAAAGUAUUUAUUUUUUC 23

N 1303K-248 2470

CFTR-

- GCUAUAGAAAGUAUUUAUUUUUUC 24

N 1303K-249 2471

CFTR-

- AAAUAUGGAAAGUUGCAG 18

N 1303K-250 2472

CFTR-

- GAAAUAUGGAAAGUUGCAG 19

N 1303K-251 2473

CFTR-

- AGAAAUAUGGAAAGUUGCAG 20

N 1303K-252 2474

CFTR-

- A AG AAA U A U G G A A AG U U G C AG 21

N 1303K-253 2475

CFTR-

- C A AG AAA U A U G G A A AG U U G C AG 22

N 1303K-254 2476

CFTR-

- UCAAGAAAUAUGGAAAGUUGCAG 23

N 1303K-255 2477

CFTR-

- AUCAAGAAAUAUGGAAAGUUGCAG 24

N 1303K-256 2478

CFTR-

- AUGAUAAAAUAUUAAAAU 18

N 1303K-257 2479

CFTR-

- CAUGAUAAAAUAUUAAAAU 19

N 1303K-258 2480

CFTR-

- ACAUGAUAAAAUAUUAAAAU 20

N 1303K-259 2481

CFTR-

- GUGGAGUGAUCAAGAAAU 18

N 1303K-260 2482

CFTR-

- AGUGGAGUGAUCAAGAAAU 19

N 1303K-261 2483

CFTR-

- CAGUGGAGUGAUCAAGAAAU 20

N 1303K-262 2484

CFTR-

- ACAGUGGAGUGAUCAAGAAAU 21

N 1303K-263 2485

CFTR- - AACAGUGGAGUGAUCAAGAAAU 22 2486

294

5535.1 N1303K-264

CFTR-

- GAACAGUGGAGUGAUCAAGAAAU 23

N 1303K-265 2487

CFTR-

- UGAACAGUGGAGUGAUCAAGAAAU 24

N 1303K-266 2488

CFTR-

- AAU AU U U U ACAAU ACAAU 18

N 1303K-267 2489

CFTR-

- AAAU AU U U U ACAAU ACAAU 19

N 1303K-268 2490

CFTR-

- G AAAU AU U U U ACAAU ACAAU 20

N 1303K-269 2491

CFTR-

- UG AAAU AU U U U ACAAU ACAAU 21

N 1303K-270 2492

CFTR-

- U U G AAAU AU U U U ACAAU ACAAU 22

N 1303K-271 2493

CFTR-

- CU U G AAAU AU U U U ACAAU ACAAU 23

N 1303K-272 2494

CFTR-

- ACUUGAAAUAUUUUACAAUACAAU 24

N 1303K-273 2495

CFTR-

- GAAAAAAGUUGGAUCCCU 18

N 1303K-274 2496

CFTR-

- AGAAAAAAGUUGGAUCCCU 19

N 1303K-275 2497

CFTR-

- UAGAAAAAAGUUGGAUCCCU 20

N 1303K-276 2498

CFTR-

- UUAGAAAAAAGUUGGAUCCCU 21

N 1303K-277 2499

CFTR-

- UUUAGAAAAAAGUUGGAUCCCU 22

N 1303K-278 2500

CFTR-

- AU U U AG AAAAAAG UUGGAUCCCU 23

N 1303K-279 2501

CFTR-

- CAU U U AG AAAAAAG UUGGAUCCCU 24

N 1303K-280 2502

CFTR-

- UAUUUUUUCUGGAACAUU 18

N 1303K-281 2503

CFTR-

- UUAUUUUUUCUGGAACAUU 19

N 1303K-282 2504

CFTR-

- UUUAUUUUUUCUGGAACAUU 20

N 1303K-283 2505

CFTR-

- AUUUAUUUUUUCUGGAACAUU 21

N 1303K-284 2506

CFTR-

- UAUUUAUUUUUUCUGGAACAUU 22

N 1303K-285 2507

295

5535.1 CFTR-

- GUAUUUAUUUUUUCUGGAACAUU 23

N1303K-286 2508

CFTR-

- AGUAUUUAUUUUUUCUGGAACAUU 24

N1303K-287 2509

CFTR-

- CUGCUAACUGAAAUGAUU 18

N1303K-288 2510

CFTR-

- GCUGCUAACUGAAAUGAUU 19

N1303K-289 2511

CFTR-

- GGCUGCUAACUGAAAUGAUU 20

N1303K-290 2512

CFTR-

- AGGCUGCUAACUGAAAUGAUU 21

N1303K-291 2513

CFTR-

- AAGGCUGCUAACUGAAAUGAUU 22

N1303K-292 2514

CFTR-

- UAAGGCUGCUAACUGAAAUGAUU 23

N1303K-293 2515

CFTR-

- GUAAGGCUGCUAACUGAAAUGAUU 24

N1303K-294 2516

CFTR-

- G AU AAAAU AU UAAAAU U U 18

N1303K-295 2517

CFTR-

- UG AU AAAAU AU UAAAAU U U 19

N1303K-296 2518

CFTR-

- AUG AU AAAAU AU UAAAAU U U 20

N1303K-297 2519

CFTR-

- AGAAAGUAUUUAUUUUUU 18

N1303K-298 2520

CFTR-

- UAGAAAGUAUUUAUUUUUU 19

N1303K-299 2521

CFTR-

- AUAGAAAGUAUUUAUUUUUU 20

N1303K-300 2522

CFTR-

- UAUAGAAAGUAUUUAUUUUUU 21

N1303K-301 2523

CFTR-

- CUAUAGAAAGUAUUUAUUUUUU 22

N1303K-302 2524

CFTR-

- GCUAUAGAAAGUAUUUAUUUUUU 23

N1303K-303 2525

CFTR-

- UGCUAUAGAAAGUAUUUAUUUUUU 24

N1303K-304 2526

Table 21A provides exemplary targeting domains for correcting a mutation (e.g., N1303K) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., N1303K), have a high level of orthogonality and start

296

5535.1 with a 5'G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 21A

Table 21B provides exemplary targeting domains for correcting a mutation (e.g., N1303K) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., N1303K) and have a high level of

orthogonality. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 21B

Table 22A provides exemplary targeting domains for correcting a mutation (e.g., Rl 17H) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., Rl 17H), have a high level of orthogonality and start with a 5'G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 22A

I 1st Tier I

297

5535.1 Target Site gRNA Name DNA Strand Targeting Domain

Length Seq ID

CFTR-R117H-1 + GUGAUGAAGGCCAAAAA 17 2529

CFTR-R117H-2 + GGUGACUUCCUACAAAA 17 2530

CFTR-R117H-3 + GCCAUGGGGCCUGUGCA 17 2531

CFTR-R117H-4 + GCAUUCCAAUGUGAUGA 17 2532

CFTR-R117H-5 - GUAAUACUUCCUUGCAC 17 2533

CFTR-R117H-6 + GUGACUUCCUACAAAAG 17 2534

CFTR-R117H-7 - GCCUUCUCUUUAUUGUG 17 2535

CFTR-R117H-8 - GCGAUUUAUCUAGGCAU 17 2536

CFTR-R117H-9 - GUACAGCCUCUCUUACU 17 2537

CFTR-R117H-10 + GAAGGCCAAAAAUGGCU 17 2538

CFTR-R117H-11 + GAGAGGCUGUACUGCUU 17 2539

CFTR-R117H-12 + GAUACAGAAUAUAUGUGCCA 20 2540

CFTR-R117H-13 - GUCUUGUGUUGAAAUUCUCA 20 2541

CFTR-R117H-14 + GUGUCCUCACAAUAAAGAGA 20 2542

CFTR-R117H-15 - GCAGUACAGCCUCUCUUACU 20 2543

CFTR-R117H-16 + GAUGAAGGCCAAAAAUGGCU 20 2544

CFTR-R117H-17 + GGCCAAAAAUGGCUGGGUGU 20 2545

Table 22B provides exemplary targeting domains for correcting a mutation (e.g., Rl 17H) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., Rl 17H) and have a high level of orthogonality. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 22B

298

5535.1 CFTR-R117H-

+ UCCUCACAAUAAAGAGA 17

22 2550

CFTR-R117H-

- AGUACAGCCUCUCUUAC 17

23 2551

CFTR-R117H-

- CAUAGCUUCCUAUGACC 17

24 2552

CFTR-R117H-

+ UGAAGGCCAAAAAUGGC 17

25 2553

CFTR-R117H-

+ UGUUCCUCCUUGUUAUC 17

26 2554

CFTR-R117H-

- CUUGUGUUGAAAUUCUC 17

27 2555

CFTR-R117H-

+ AUUCUUCCCAGUAAGAG 17

28 2556

CFTR-R117H-

+ AGACUUUUCAUCUUUAG 17

29 2557

CFTR-R117H-

- UGACCCGGAUAACAAGG 17

30 2558

CFTR-R117H-

- UUUGGCCUUCAUCACAU 17

31 2559

CFTR-R117H-

+ CAGAAUAUAUGUGCCAU 17

32 2560

CFTR-R117H-

+ CUUGUUAUCCGGGUCAU 17

33 2561

CFTR-R117H-

- UCUAUCGCGAUUUAUCU 17

34 2562

CFTR-R117H-

+ CAAAAAUGGCUGGGUGU 17

35 2563

CFTR-R117H-

- CUACACCCAGCCAUUUU 17

36 2564

CFTR-R117H-

+ AAUGUGAUGAAGGCCAAAAA 20

37 2565

CFTR-R117H-

+ UUUGGUGACUUCCUACAAAA 20

38 2566

CFTR-R117H-

+ CUUUGGUGACUUCCUACAAA 20

39 2567

CFTR-R117H-

- UUCCUAUGACCCGGAUAACA 20

40 2568

CFTR-R117H-

- ACUUCCUUGCACAGGCCCCA 20

41 2569

CFTR-R117H-

+ UGUGCCAUGGGGCCUGUGCA 20

42 2570

CFTR-R117H- + UCUGCAUUCCAAUGUGAUGA 20 2571

299

5535.1 43

CFTR-R117H-

- AAGGUAAUACUUCCUUGCAC 20

44 2572

CFTR-R117H-

- AGCAGUACAGCCUCUCU UAC 20

45 2573

CFTR-R117H-

- AAUCAUAGCUUCCUAUGACC 20

46 2574

CFTR-R117H-

+ UGAUGAAGGCCAAAAAUGGC 20

47 2575

CFTR-R117H-

- AGUCUUGUGUUGAAAUUCUC 20

48 2576

CFTR-R117H-

+ U UGGUGACUUCCUACAAAAG 20

49 2577

CFTR-R117H-

+ AUGAUUCUUCCCAGUAAGAG 20

50 2578

CFTR-R117H-

+ CUUAAAAUGAGUUUAUAUAG 20

51 2579

CFTR-R117H-

+ ACAAGACUU UUCAUCUU UAG 20

52 2580

CFTR-R117H-

- CUAUGACCCGGAUAACAAGG 20

53 2581

CFTR-R117H-

+ UACAGAAUAUAUGUGCCAUG 20

54 2582

CFTR-R117H-

- UAUGCCUUCUCUUUAU UGUG 20

55 2583

CFTR-R117H-

- AUUUUUGGCCUUCAUCACAU 20

56 2584

CFTR-R117H-

+ AUACAGAAUAUAUGUGCCAU 20

57 2585

CFTR-R117H-

- AUCGCGAUUUAUCUAGGCAU 20

58 2586

CFTR-R117H-

+ CUCCUUGUUAUCCGGGUCAU 20

59 2587

CFTR-R117H-

+ UAAGAGAGGCUGUACUGCUU 20

60 2588

CFTR-R117H-

- CUCCUACACCCAGCCAU UUU 20

61 2589

Table 22C provides exemplary targeting domains for correcting a mutation (e.g., Rl 17H) in the CFTR gene selected according to the third tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., Rl 17H) and start with a 5'G. It is contemplated herein that

300

5535.1 in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 22C

Table 22D provides exemplary targeting domains for correcting a mutation (e.g., Rl 17H) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., Rl 17H). It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 22D

301

5535.1 71

CFTR-R117H-

+ AGUGUUCCUCCUUGUUAUCC 20

72 2600

CFTR-R117H-

- CACUCUAUCGCGAUUUAUCU 20

73 2601

CFTR-R117H-

- CUCUGUUUUUCCCCUUUUGU 20

74 2602

Table 23A provides exemplary targeting domains for correcting a mutation (e.g., Rl 17H) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., Rl 17H), have a high level of orthogonality, start with a 5'G, and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 23A

302

5535.1 CFTR-R117H-

- GAAAAGUCUUGUGUUGAAAUUCU 23

85 2613

Table 23B provides exemplary targeting domains for correcting a mutation (e.g., Rl 17H) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., Rl 17H), have a high level of orthogonality and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 23B

303

5535.1 98

CFTR-R117H-

+ AUUAAAACAUGUACGAUA 18

99 2627

CFTR-R117H-

+ CAUUAAAACAUGUACGAUA 19

100 2628

CFTR-R117H-

+ ACAUUAAAACAUGUACGAUA 20

101 2629

CFTR-R117H-

+ UUAAAAUGAGUUUAUAUA 18

102 2630

CFTR-R117H-

+ CUUAAAAUGAGUUUAUAUA 19

103 2631

CFTR-R117H-

+ ACUUAAAAUGAGUUUAUAUA 20

104 2632

CFTR-R117H-

+ UGAUGAAGGCCAAAAAUGG 19

105 2633

CFTR-R117H-

+ UGUGAUGAAGGCCAAAAAUGG 21

106 2634

CFTR-R117H-

+ AUGUGAUGAAGGCCAAAAAUGG 22

107 2635

CFTR-R117H-

+ AAUGUGAUGAAGGCCAAAAAUGG 23

108 2636

CFTR-R117H-

+ CAAUGUGAUGAAGGCCAAAAAUGG 24

109 2637

CFTR-R117H-

+ UUUCUCAUAAAAUACCCU 18

110 2638

CFTR-R117H-

+ AUUUCUCAUAAAAUACCCU 19

111 2639

CFTR-R117H-

+ UAUUUCUCAUAAAAUACCCU 20

112 2640

CFTR-R117H-

- AUCAUAGCUUCCUAUGAC 18

113 2641

CFTR-R117H-

- AAUCAUAGCUUCCUAUGAC 19

114 2642

CFTR-R117H-

- AGAAUCAUAGCUUCCUAUGAC 21

115 2643

CFTR-R117H-

- AAGAAUCAUAGCUUCCUAUGAC 22

116 2644

CFTR-R117H-

- ACAGCCUCUCUUACUGGG 18

117 2645

CFTR-R117H-

- UACAGCCUCUCUUACUGGG 19

118 2646

CFTR-R117H-

- AGUACAGCCUCUCUUACUGGG 21

119 2647

304

5535.1 CFTR-R117H-

- CAGUACAGCCUCUCUUACUGGG 22

120 2648

CFTR-R117H-

- AGCAGUACAGCCUCUCUUACUGGG 24

121 2649

CFTR-R117H-

- UUUUGGCCUUCAUCACAU 18

122 2650

CFTR-R117H-

- UUUUUGGCCUUCAUCACAU 19

123 2651

CFTR-R117H-

- AUUUUUGGCCUUCAUCACAU 20

56 2584

CFTR-R117H-

- CAUUUUUGGCCUUCAUCACAU 21

124 2652

CFTR-R117H-

- CCAUUUUUGGCCUUCAUCACAU 22

125 2653

CFTR-R117H-

- AGCCAUUUUUGGCCUUCAUCACAU 24

126 2654

CFTR-R117H-

- AGUCUUGUGUUGAAAUUCU 19

127 2655

CFTR-R117H-

- AAGUCUUGUGUUGAAAUUCU 20

128 2656

CFTR-R117H-

- AAAGUCUUGUGUUGAAAUUCU 21

129 2657

CFTR-R117H-

- AAAAGUCUUGUGUUGAAAUUCU 22

130 2658

CFTR-R117H-

- UGAAAAGUCUUGUGUUGAAAUUCU 24

131 2659

Table 23C provides exemplary targeting domains for correcting a mutation (e.g., Rl 17H) in the CFTR gene selected according to the third tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., Rl 17H), start with a 5'G and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 23C

305

5535.1 132

CFTR-R117H-

+ GAGACUUAAAAUGAGUUUAUAUA 23

133 2661

CFTR-R117H-

+ GGAGACUUAAAAUGAGUUUAUAUA 24

134 2662

CFTR-R117H-

+ GAGUGUUCCUCCUUGUUAU 19

135 2663

CFTR-R117H-

+ GAUAGAGUGUUCCUCCUUGUUAU 23

136 2664

Table 23D provides exemplary targeting domains for correcting a mutation (e.g., Rl 17H) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., Rl 17H), and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through

complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 23D

306

5535.1 CFTR-R117H-

+ CAUUUAUUUCUCAUAAAAUACCCU 24

146 2674

CFTR-R117H-

- UCACAUUGGAAUGCAGAU 18

147 2675

CFTR-R117H-

- AUCACAUUGGAAUGCAGAU 19

148 2676

CFTR-R117H-

- CAUCACAUUGGAAUGCAGAU 20

149 2677

CFTR-R117H-

- UCAUCACAUUGGAAUGCAGAU 21

150 2678

CFTR-R117H-

- UUCAUCACAUUGGAAUGCAGAU 22

151 2679

CFTR-R117H-

- CUUCAUCACAUUGGAAUGCAGAU 23

152 2680

CFTR-R117H-

- CCUUCAUCACAUUGGAAUGCAGAU 24

153 2681

Table 23E provides exemplary targeting domains for correcting a mutation (e.g., Rl 17H) in the CFTR gene selected according to the fifth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., Rl 17H), and PAM is NNGRRV. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through

complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 23E

307

5535.1 159

CFTR-R117H-

+ UGACUUCCUACAAAAGGGGAAAAA 24

160 2688

CFTR-R117H-

+ UGGUGACUUCCUACAAAA 18

161 2689

CFTR-R117H-

+ UUGGUGACUUCCUACAAAA 19

162 2690

CFTR-R117H-

+ UUUGGUGACUUCCUACAAAA 20

38 2566

CFTR-R117H-

+ CUUUGGUGACUUCCUACAAAA 21

163 2691

CFTR-R117H-

+ GCUUUGGUGACUUCCUACAAAA 22

164 2692

CFTR-R117H-

+ UGCUUUGGUGACUUCCUACAAAA 23

165 2693

CFTR-R117H-

+ CUGCUUUGGUGACUUCCUACAAAA 24

166 2694

CFTR-R117H-

+ UUGGUGACUUCCUACAAA 18

167 2695

CFTR-R117H-

+ UUUGGUGACUUCCUACAAA 19

168 2696

CFTR-R117H-

+ CUUUGGUGACUUCCUACAAA 20

39 2567

CFTR-R117H-

+ GCUUUGGUGACUUCCUACAAA 21

169 2697

CFTR-R117H-

+ UGCUUUGGUGACUUCCUACAAA 22

170 2698

CFTR-R117H-

+ CUGCUUUGGUGACUUCCUACAAA 23

171 2699

CFTR-R117H-

+ ACUGCUUUGGUGACUUCCUACAAA 24

172 2700

CFTR-R117H-

+ CAGUGUCCUCACAAUAAA 18

173 2701

CFTR-R117H-

+ GCAGUGUCCUCACAAUAAA 19

174 2702

CFTR-R117H-

+ AGCAGUGUCCU C ACAAU AAA 20

175 2703

CFTR-R117H-

+ G AG C AG U G U CC U C ACAA U AAA 21

176 2704

CFTR-R117H-

+ GGAGCAGUGUCCUCACAAUAAA 22

177 2705

CFTR-R117H-

+ AGGAGCAGUGUCCUCACAAU AAA 23

178 2706

308

5535.1 CFTR-R117H-

+ UAGGAGCAGUGUCCUCACAAUAAA 24

179 2707

CFTR-R117H-

+ UUUGGUGACUUCCUACAA 18

180 2708

CFTR-R117H-

+ CUUUGGUGACUUCCUACAA 19

181 2709

CFTR-R117H-

+ GCUUUGGUGACUUCCUACAA 20

182 2710

CFTR-R117H-

+ UGCUUUGGUGACUUCCUACAA 21

183 2711

CFTR-R117H-

+ CUGCUUUGGUGACUUCCUACAA 22

184 2712

CFTR-R117H-

+ ACUGCUUUGGUGACUUCCUACAA 23

185 2713

CFTR-R117H-

+ UACUGCUUUGGUGACUUCCUACAA 24

186 2714

CFTR-R117H-

+ UAUGAUUCUUCCCAGUAA 18

187 2715

CFTR-R117H-

+ CUAUGAUUCUUCCCAGUAA 19

188 2716

CFTR-R117H-

+ GCUAUGAUUCUUCCCAGUAA 20

189 2717

CFTR-R117H-

+ AGCUAUGAUUCUUCCCAGUAA 21

190 2718

CFTR-R117H-

+ AAGCUAUGAUUCUUCCCAGUAA 22

191 2719

CFTR-R117H-

+ GAAGCUAUGAUUCUUCCCAGUAA 23

192 2720

CFTR-R117H-

+ GGAAGCUAUGAUUCUUCCCAGUAA 24

193 2721

CFTR-R117H-

+ U ACAAAAG GG G AAAAAC A 18

194 2722

CFTR-R117H-

+ CUACAAAAGGGGAAAAACA 19

195 2723

CFTR-R117H-

+ CCUACAAAAGGGGAAAAACA 20

196 2724

CFTR-R117H-

+ UCCUACAAAAGGGGAAAAACA 21

197 2725

CFTR-R117H-

+ UUCCUACAAAAGGGGAAAAACA 22

198 2726

CFTR-R117H-

+ CUUCCUACAAAAGGGGAAAAACA 23

199 2727

CFTR-R117H- + ACUUCCUACAAAAGGGGAAAAACA 24 2728

309

5535.1 200

CFTR-R117H-

+ UACAGAAUAUAUGUGCCA 18

201 2729

CFTR-R117H-

+ AUACAGAAUAUAUGUGCCA 19

202 2730

CFTR-R117H-

+ GAUACAGAAUAUAUGUGCCA 20

12 2540

CFTR-R117H-

+ CGAUACAGAAUAUAUGUGCCA 21

203 2731

CFTR-R117H-

+ ACGAUACAGAAUAUAUGUGCCA 22

204 2732

CFTR-R117H-

+ UACGAUACAGAAUAUAUGUGCCA 23

205 2733

CFTR-R117H-

+ GUACGAUACAGAAUAUAUGUGCCA 24

206 2734

CFTR-R117H-

+ UGCCAUGGGGCCUGUGCA 18

207 2735

CFTR-R117H-

+ GUGCCAUGGGGCCUGUGCA 19

208 2736

CFTR-R117H-

+ UGUGCCAUGGGGCCUGUGCA 20

42 2570

CFTR-R117H-

+ AUGUGCCAUGGGGCCUGUGCA 21

209 2737

CFTR-R117H-

+ UAUGUGCCAUGGGGCCUGUGCA 22

210 2738

CFTR-R117H-

+ AUAUGUGCCAUGGGGCCUGUGCA 23

211 2739

CFTR-R117H-

+ UAUAUGUGCCAUGGGGCCUGUGCA 24

212 2740

CFTR-R117H-

+ UCCUUGUUAUCCGGGUCA 18

213 2741

CFTR-R117H-

+ CUCCUUGUUAUCCGGGUCA 19

214 2742

CFTR-R117H-

+ CCUCCUUGUUAUCCGGGUCA 20

215 2743

CFTR-R117H-

+ UCCUCCUUGUUAUCCGGGUCA 21

216 2744

CFTR-R117H-

+ UUCCUCCUUGUUAUCCGGGUCA 22

217 2745

CFTR-R117H-

+ GUUCCUCCUUGUUAUCCGGGUCA 23

218 2746

CFTR-R117H-

+ UGUUCCUCCUUGUUAUCCGGGUCA 24

219 2747

310

5535.1 CFTR-R117H-

+ AGCAGUGUCCUCACAAUA 18

220 2748

CFTR-R117H-

+ GAGCAGUGUCCUCACAAUA 19

221 2749

CFTR-R117H-

+ GGAGCAGUGUCCUCACAAUA 20

222 2750

CFTR-R117H-

+ AGGAGCAGUGUCCUCACAAUA 21

223 2751

CFTR-R117H-

+ UAGGAGCAGUGUCCUCACAAUA 22

224 2752

CFTR-R117H-

+ GU AGGAGCAGUGUCCUCACAAUA 23

225 2753

CFTR-R117H-

+ UGUAGGAGCAGUGUCCUCACAAUA 24

226 2754

CFTR-R117H-

+ ACUUAAAAUGAGUUUAUA 18

227 2755

CFTR-R117H-

+ GACUUAAAAUGAGUUUAUA 19

228 2756

CFTR-R117H-

+ AGACUUAAAAUGAGUUUAUA 20

229 2757

CFTR-R117H-

+ GAGACUUAAAAUGAGUUUAUA 21

230 2758

CFTR-R117H-

+ GGAGACUUAAAAUGAGUUUAUA 22

231 2759

CFTR-R117H-

+ AGGAGACUUAAAAUGAGUUUAUA 23

232 2760

CFTR-R117H-

+ GAGGAGACUUAAAAUGAGUUUAUA 24

233 2761

CFTR-R117H-

+ CAAGACUUUUCAUCUUUA 18

234 2762

CFTR-R117H-

+ ACAAGACUUUUCAUCUUUA 19

235 2763

CFTR-R117H-

+ CACAAG ACU UUUCAUCUUUA 20

236 2764

CFTR-R117H-

+ ACACAAGACUUUUCAUCUUUA 21

237 2765

CFTR-R117H-

+ AACACAAGACUUUUCAUCUUUA 22

238 2766

CFTR-R117H-

+ CAACACAAG ACU U UUCAUCUUUA 23

239 2767

CFTR-R117H-

+ U CAACACAAG ACU UUUCAUCUUUA 24

240 2768

CFTR-R117H- + UAUUUCUCAUAAAAUACC 18 2769

311

5535.1 241

CFTR-R117H-

+ UUAUUUCUCAUAAAAUACC 19

242 2770

CFTR-R117H-

+ UUUAUUUCUCAUAAAAUACC 20

243 2771

CFTR-R117H-

+ AUUUAUUUCUCAUAAAAUACC 21

244 2772

CFTR-R117H-

+ CAUUUAUUUCUCAUAAAAUACC 22

245 2773

CFTR-R117H-

+ UCAUUUAUUUCUCAUAAAAUACC 23

246 2774

CFTR-R117H-

+ UUCAUUUAUUUCUCAUAAAAUACC 24

247 2775

CFTR-R117H-

+ AUACAGAAUAUAUGUGCC 18

248 2776

CFTR-R117H-

+ GAUACAGAAUAUAUGUGCC 19

249 2777

CFTR-R117H-

+ CGAUACAGAAUAUAUGUGCC 20

250 2778

CFTR-R117H-

+ ACGAUACAGAAUAUAUGUGCC 21

251 2779

CFTR-R117H-

+ UACGAUACAGAAUAUAUGUGCC 22

252 2780

CFTR-R117H-

+ GUACGAUACAGAAUAUAUGUGCC 23

253 2781

CFTR-R117H-

+ UGUACGAUACAGAAUAUAUGUGCC 24

254 2782

CFTR-R117H-

+ GUGCCAUGGGGCCUGUGC 18

255 2783

CFTR-R117H-

+ UGUGCCAUGGGGCCUGUGC 19

256 2784

CFTR-R117H-

+ AUGUGCCAUGGGGCCUGUGC 20

257 2785

CFTR-R117H-

+ UAUGUGCCAUGGGGCCUGUGC 21

258 2786

CFTR-R117H-

+ AUAUGUGCCAUGGGGCCUGUGC 22

259 2787

CFTR-R117H-

+ UAUAUGUGCCAUGGGGCCUGUGC 23

260 2788

CFTR-R117H-

+ AUAUAUGUGCCAUGGGGCCUGUGC 24

261 2789

CFTR-R117H-

+ GGUGACUUCCUACAAAAG 18

262 2790

312

5535.1 CFTR-R117H-

+ UGGUGACUUCCUACAAAAG 19

263 2791

CFTR-R117H-

+ UUGGUGACUUCCUACAAAAG 20

49 2577

CFTR-R117H-

+ UUUGGUGACUUCCUACAAAAG 21

264 2792

CFTR-R117H-

+ CUUUGGUGACUUCCUACAAAAG 22

265 2793

CFTR-R117H-

+ GCUUUGGUGACUUCCUACAAAAG 23

266 2794

CFTR-R117H-

+ UGCUUUGGUGACUUCCUACAAAAG 24

267 2795

CFTR-R117H-

+ AAGACUUUUCAUCUUUAG 18

268 2796

CFTR-R117H-

+ CAAGACUUUUCAUCUUUAG 19

269 2797

CFTR-R117H-

+ ACAAGACUUUUCAUCUUUAG 20

52 2580

CFTR-R117H-

+ CACAAGACUUUUCAUCUUUAG 21

270 2798

CFTR-R117H-

+ ACA CAAGACUUUUCAUCUUUAG 22

271 2799

CFTR-R117H-

+ AACACAAG ACU U UUCAUCUUUAG 23

272 2800

CFTR-R117H-

+ CAACACAAG ACU U UUCAUCUUUAG 24

273 2801

CFTR-R117H-

+ GCCAAAAAUGGCUGGGUG 18

274 2802

CFTR-R117H-

+ GGCCAAAAAUGGCUGGGUG 19

275 2803

CFTR-R117H-

+ AGGCCAAAAAUGGCUGGGUG 20

276 2804

CFTR-R117H-

+ AAGGCCAAAAAUGGCUGGGUG 21

277 2805

CFTR-R117H-

+ GAAGGCCAAAAAUGGCUGGGUG 22

278 2806

CFTR-R117H-

+ UGAAGGCCAAAAAUGGCUGGGUG 23

279 2807

CFTR-R117H-

+ AUGAAGGCCAAAAAUGGCUGGGUG 24

280 2808

CFTR-R117H-

+ CAUCUGCAUUCCAAUGUG 18

281 2809

CFTR-R117H- + UCAUCUGCAUUCCAAUGUG 19 2810

313

5535.1 282

CFTR-R117H-

+ CUCAUCUGCAUUCCAAUGUG 20

283 2811

CFTR-R117H-

+ UCUCAUCUGCAUUCCAAUGUG 21

284 2812

CFTR-R117H-

+ UUCUCAUCUGCAUUCCAAUGUG 22

285 2813

CFTR-R117H-

+ AUUCUCAUCUGCAUUCCAAUGUG 23

286 2814

CFTR-R117H-

+ UAUUCUCAUCUGCAUUCCAAUGUG 24

287 2815

CFTR-R117H-

+ CCUUGUUAUCCGGGUCAU 18

288 2816

CFTR-R117H-

+ UCCUUGUUAUCCGGGUCAU 19

289 2817

CFTR-R117H-

+ CUCCUUGUUAUCCGGGUCAU 20

59 2587

CFTR-R117H-

+ CCUCCUUGUUAUCCGGGUCAU 21

290 2818

CFTR-R117H-

+ UCCUCCUUGUUAUCCGGGUCAU 22

291 2819

CFTR-R117H-

+ UUCCUCCUUGUUAUCCGGGUCAU 23

292 2820

CFTR-R117H-

+ GUUCCUCCUUGUUAUCCGGGUCAU 24

293 2821

CFTR-R117H-

+ GCUAUGAUUCUUCCCAGU 18

294 2822

CFTR-R117H-

+ AGCUAUGAUUCUUCCCAGU 19

295 2823

CFTR-R117H-

+ AAGCUAUGAUUCUUCCCAGU 20

296 2824

CFTR-R117H-

+ GAAGCUAUGAUUCUUCCCAGU 21

297 2825

CFTR-R117H-

+ GGAAGCUAUGAUUCUUCCCAGU 22

298 2826

CFTR-R117H-

+ AGGAAGCUAUGAUUCUUCCCAGU 23

299 2827

CFTR-R117H-

+ UAGGAAGCUAUGAUUCUUCCCAGU 24

300 2828

CFTR-R117H-

+ CCAAAAAUGGCUGGGUGU 18

301 2829

CFTR-R117H-

+ GCCAAAAAUGGCUGGGUGU 19

302 2830

314

5535.1 CFTR-R117H-

+ GGCCAAAAAUGGCUGGGUGU 20

17 2545

CFTR-R117H-

+ AGGCCAAAAAUGGCUGGGUGU 21

303 2831

CFTR-R117H-

+ AAGGCCAAAAAUGGCUGGGUGU 22

304 2832

CFTR-R117H-

+ GAAGGCCAAAAAUGGCUGGGUGU 23

305 2833

CFTR-R117H-

+ UGAAGGCCAAAAAUGGCUGGGUGU 24

306 2834

CFTR-R117H-

+ CACAAGACUUUUCAUCUU 18

307 2835

CFTR-R117H-

+ ACACAAGACUUUUCAUCUU 19

308 2836

CFTR-R117H-

+ AACACAAG ACU U U U CAU CU U 20

309 2837

CFTR-R117H-

+ CAACACAAG ACU UUUCAUCUU 21

310 2838

CFTR-R117H-

+ UCAACACAAGACUUUUCAUCUU 22

311 2839

CFTR-R117H-

+ U U CAACACAAG AC U UUUCAUCUU 23

312 2840

CFTR-R117H-

+ U U U CAACACAAG AC U UUUCAUCUU 24

313 2841

CFTR-R117H-

- GUAUUUUAUGAGAAAUAA 18

314 2842

CFTR-R117H-

- GGUAUUUUAUGAGAAAUAA 19

315 2843

CFTR-R117H-

- GGGUAUUUUAUGAGAAAUAA 20

316 2844

CFTR-R117H-

- AGGGUAUUUUAUGAGAAAUAA 21

317 2845

CFTR-R117H-

- CAGGGUAUUUUAUGAGAAAUAA 22

318 2846

CFTR-R117H-

- UCAGGGUAUUUUAUGAGAAAUAA 23

319 2847

CFTR-R117H-

- CUCAGGGUAUUUUAUGAGAAAUAA 24

320 2848

CFTR-R117H-

- CCUAUGACCCGGAUAACA 18

321 2849

CFTR-R117H-

- UCCUAUGACCCGGAUAACA 19

322 2850

CFTR-R117H- - UUCCUAUGACCCGGAUAACA 20 2568

315

5535.1 40

CFTR-R117H-

- CUUCCUAUGACCCGGAUAACA 21

323 2851

CFTR-R117H-

- GCUUCCUAUGACCCGGAUAACA 22

324 2852

CFTR-R117H-

- AGCU UCCUAUGACCCGGAUAACA 23

325 2853

CFTR-R117H-

- UAGCUUCCUAUGACCCGGAUAACA 24

326 2854

CFTR-R117H-

- UU UUUGGCCUUCAUCACA 18

327 2855

CFTR-R117H-

- AUUUUUGGCCUUCAUCACA 19

328 2856

CFTR-R117H-

- CAU UUUUGGCCUUCAUCACA 20

329 2857

CFTR-R117H-

- CCAUU UUUGGCCU UCAUCACA 21

330 2858

CFTR-R117H-

- GCCAUUUUUGGCCUUCAUCACA 22

331 2859

CFTR-R117H-

- AGCCAUUUUUGGCCUUCAUCACA 23

332 2860

CFTR-R117H-

- CAGCCAUUUU UGGCCUUCAUCACA 24

333 2861

CFTR-R117H-

- GCAGUACAGCCUCUCU UA 18

334 2862

CFTR-R117H-

- AGCAGUACAGCCUCUCU UA 19

335 2863

CFTR-R117H-

- AAGCAGUACAGCCUCUCUUA 20

336 2864

CFTR-R117H-

- AAAGCAGUACAGCCUCUCUUA 21

337 2865

CFTR-R117H-

- CAAAGCAGUACAGCCUCUCUUA 22

338 2866

CFTR-R117H-

- CCAAAGCAGUACAGCCUCUCUUA 23

339 2867

CFTR-R117H-

- ACCAAAGCAGUACAGCCUCUCUUA 24

340 2868

CFTR-R117H-

- UCCUAUGACCCGGAUAAC 18

341 2869

CFTR-R117H-

- UUCCUAUGACCCGGAUAAC 19

342 2870

CFTR-R117H-

- CUUCCUAUGACCCGGAUAAC 20

343 2871

316

5535.1 CFTR-R117H-

- GCUUCCUAUGACCCGGAUAAC 21

344 2872

CFTR-R117H-

- AGCUUCCUAUGACCCGGAUAAC 22

345 2873

CFTR-R117H-

- UAGCUUCCUAUGACCCGGAUAAC 23

346 2874

CFTR-R117H-

- AUAGCUUCCUAUGACCCGGAUAAC 24

347 2875

CFTR-R117H-

- CAGUACAGCCUCUCUUAC 18

348 2876

CFTR-R117H-

- GCAGUACAGCCUCUCU UAC 19

349 2877

CFTR-R117H-

- AGCAGUACAGCCUCUCUUAC 20

45 2573

CFTR-R117H-

- AAGCAGUACAGCCUCUCUUAC 21

350 2878

CFTR-R117H-

- AAAGCAGUACAGCCUCUCUUAC 22

351 2879

CFTR-R117H-

- CAAAGCAGUACAGCCUCUCUUAC 23

352 2880

CFTR-R117H-

- CCAAAGCAGUACAGCCUCUCUUAC 24

353 2881

CFTR-R117H-

- UUUAAGUCUCCUCUAAAG 18

354 2882

CFTR-R117H-

- UUUUAAGUCUCCUCUAAAG 19

355 2883

CFTR-R117H-

- AUUUUAAGUCUCCUCUAAAG 20

356 2884

CFTR-R117H-

- CAU UUUAAGUCUCCUCUAAAG 21

357 2885

CFTR-R117H-

- UCAUUUUAAGUCUCCUCUAAAG 22

358 2886

CFTR-R117H-

- CUCAUUUUAAGUCUCCUCUAAAG 23

359 2887

CFTR-R117H-

- ACUCAUUUUAAGUCUCCUCUAAAG 24

360 2888

CFTR-R117H-

- UAUGACCCGGAUAACAAG 18

361 2889

CFTR-R117H-

- CUAUGACCCGGAUAACAAG 19

362 2890

CFTR-R117H-

- CCUAUGACCCGGAUAACAAG 20

363 2891

CFTR-R117H- - UCCUAUGACCCGGAUAACAAG 21 2892

317

5535.1 364

CFTR-R117H-

- UUCCUAUGACCCGGAUAACAAG 22

365 2893

CFTR-R117H-

- CUUCCUAUGACCCGGAUAACAAG 23

366 2894

CFTR-R117H-

- GCUUCCUAUGACCCGGAUAACAAG 24

367 2895

CFTR-R117H-

- CAUCACAUUGGAAUGCAG 18

368 2896

CFTR-R117H-

- UCAUCACAUUGGAAUGCAG 19

369 2897

CFTR-R117H-

- UUCAUCACAUUGGAAUGCAG 20

370 2898

CFTR-R117H-

- CUUCAUCACAUUGGAAUGCAG 21

371 2899

CFTR-R117H-

- CCUUCAUCACAUUGGAAUGCAG 22

372 2900

CFTR-R117H-

- GCCUUCAUCACAUUGGAAUGCAG 23

373 2901

CFTR-R117H-

- GGCCUUCAUCACAUUGGAAUGCAG 24

374 2902

CFTR-R117H-

- AUGACCCGGAUAACAAGG 18

375 2903

CFTR-R117H-

- UAUGACCCGGAUAACAAGG 19

376 2904

CFTR-R117H-

- CUAUGACCCGGAUAACAAGG 20

53 2581

CFTR-R117H-

- CCUAUGACCCGGAUAACAAGG 21

377 2905

CFTR-R117H-

- UCCUAUGACCCGGAUAACAAGG 22

378 2906

CFTR-R117H-

- UUCCU AUGACCCGGAUAACAAGG 23

379 2907

CFTR-R117H-

- CUUCCUAUGACCCGGAUAACAAGG 24

380 2908

CFTR-R117H-

- AAGAUGAAAAGUCUUGUG 18

381 2909

CFTR-R117H-

- AAAGAUGAAAAGUCUUGUG 19

382 2910

CFTR-R117H-

- UAAAGAUGAAAAGUCUUGUG 20

383 2911

CFTR-R117H-

- CUAAAGAUGAAAAGUCUUGUG 21

384 2912

318

5535.1 CFTR-R117H-

- UCUAAAGAUGAAAAGUCUUGUG 22

385 2913

CFTR-R117H-

- CUCUAAAGAUGAAAAGUCUUGUG 23

386 2914

CFTR-R117H-

- CCUCUAAAGAUGAAAAGUCUUGUG 24

387 2915

CFTR-R117H-

- UCUGUUUUUCCCCUUUUG 18

388 2916

CFTR-R117H-

- CUCUGUUUUUCCCCUUUUG 19

389 2917

CFTR-R117H-

- UCUCUGUUUUUCCCCUUUUG 20

390 2918

CFTR-R117H-

- UUCUCUGUUUUUCCCCUUUUG 21

391 2919

CFTR-R117H-

- UUUCUCUGUUUUUCCCCUUUUG 22

392 2920

CFTR-R117H-

- AUUUCUCUGUUUUUCCCCUUUUG 23

393 2921

CFTR-R117H-

- AAUUUCUCUGUUUUUCCCCUUUUG 24

394 2922

CFTR-R117H-

- AUGUUUAGUUUGAUUUAU 18

395 2923

CFTR-R117H-

- UAUGUUUAGUUUGAUUUAU 19

396 2924

CFTR-R117H-

- CUAUGUUUAGUUUGAUUUAU 20

397 2925

CFTR-R117H-

- GCUAUGUUUAGUUUGAUUUAU 21

398 2926

CFTR-R117H-

- AGCUAUGUUUAGUUUGAUUUAU 22

399 2927

CFTR-R117H-

- UAGCUAUGUUUAGUUUGAUUUAU 23

400 2928

CFTR-R117H-

- AUAGCUAUGUUUAGUUUGAUUUAU 24

401 2929

CFTR-R117H-

- AUUCUCAGGGUAUUUUAU 18

402 2930

CFTR-R117H-

- AAUUCUCAGGGUAUUUUAU 19

403 2931

CFTR-R117H-

- AAAUUCUCAGGGUAUUUUAU 20

404 2932

CFTR-R117H-

- GAAAUUCUCAGGGUAUUUUAU 21

405 2933

CFTR-R117H- - UGAAAUUCUCAGGGUAUUUUAU 22 2934

319

5535.1 406

CFTR-R117H-

- UUGAAAUUCUCAGGGUAUUUUAU 23

407 2935

CFTR-R117H-

- GUUGAAAUUCUCAGGGUAUUUUAU 24

408 2936

CFTR-R117H-

- AGUACAGCCUCUCUUACU 18

409 2937

CFTR-R117H-

- CAGUACAGCCUCUCUUACU 19

410 2938

CFTR-R117H-

- GCAGUACAGCCUCUCUUACU 20

15 2543

CFTR-R117H-

- AGCAGUACAGCCUCUCUUACU 21

411 2939

CFTR-R117H-

- AAGCAGUACAGCCUCUCUUACU 22

412 2940

CFTR-R117H-

- AAAGCAGUACAGCCUCUCUUACU 23

413 2941

CFTR-R117H-

- CAAAGCAGUACAGCCUCUCUUACU 24

414 2942

CFTR-R117H-

- AUGCCUUCUCUUUAUUGU 18

415 2943

CFTR-R117H-

- UAUGCCUUCUCUUUAUUGU 19

416 2944

CFTR-R117H-

- UUAUGCCUUCUCUUUAUUGU 20

417 2945

CFTR-R117H-

- CUUAUGCCUUCUCUUUAUUGU 21

418 2946

CFTR-R117H-

- GCUUAUGCCUUCUCUUUAUUGU 22

419 2947

CFTR-R117H-

- GGCUUAUGCCUUCUCUUUAUUGU 23

420 2948

CFTR-R117H-

- AGGCUUAUGCCUUCUCUUUAUUGU 24

421 2949

CFTR-R117H-

- CUGUUUUUCCCCUUUUGU 18

422 2950

CFTR-R117H-

- UCUGUUUUUCCCCUUUUGU 19

423 2951

CFTR-R117H-

- CUCUGUUUUUCCCCUUUUGU 20

74 2602

CFTR-R117H-

- UCUCUGUUUUUCCCCUUUUGU 21

424 2952

CFTR-R117H-

- UUCUCUGUUUUUCCCCUUUUGU 22

425 2953

320

5535.1 CFTR-R117H-

- UUUCUCUGUUUUUCCCCUUUUGU 23

426 2954

CFTR-R117H-

- AUUUCUCUGUUUUUCCCCUUUUGU 24

427 2955

CFTR-R117H-

- UUAUGCCUUCUCUUUAUU 18

428 2956

CFTR-R117H-

- CUUAUGCCUUCUCUUUAUU 19

429 2957

CFTR-R117H-

- GCUUAUGCCUUCUCUUUAUU 20

430 2958

CFTR-R117H-

- GGCUUAUGCCUUCUCUUUAUU 21

431 2959

CFTR-R117H-

- AGGCUUAUGCCUUCUCUUUAUU 22

432 2960

CFTR-R117H-

- UAGGCUUAUGCCUUCUCUUUAUU 23

433 2961

CFTR-R117H-

- AUAGGCUUAUGCCUUCUCUUUAUU 24

434 2962

CFTR-R117H-

- AAAUUCUCAGGGUAUUUU 18

435 2963

CFTR-R117H-

- GAAAUUCUCAGGGUAUUUU 19

436 2964

CFTR-R117H-

- UGAAAUUCUCAGGGUAUUUU 20

437 2965

CFTR-R117H-

- UUGAAAUUCUCAGGGUAUUUU 21

438 2966

CFTR-R117H-

- GUUGAAAUUCUCAGGGUAUUUU 22

439 2967

CFTR-R117H-

- UGUUGAAAUUCUCAGGGUAUUUU 23

440 2968

CFTR-R117H-

- GUGUUGAAAUUCUCAGGGUAUUUU 24

441 2969

Table 24A provides exemplary targeting domains for correcting a mutation (e.g., Rl 17H) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., Rl 17H), have a high level of orthogonality and start with a 5'G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

321

5535.1 Table 24A

Table 24B provides exemplary targeting domains for correcting a mutation (e.g., Rl 17H) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., Rl 17H) and have a high level of orthogonality. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 24B

Table 24C provides exemplary targeting domains for correcting a mutation (e.g., Rl 17H) in the CFTR gene selected according to the third tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., Rl 17H) and start with a 5'G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9

322

5535.1 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 24C

Table 24D provides exemplary targeting domains for correcting a mutation (e.g., Rl 17H) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., Rl 17H). It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 24D

Table 25A provides exemplary targeting domains for correcting a mutation (e.g., R553X) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., R553X), have a high level of orthogonality and start with a 5'G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 25A

323

5535.1 1st Tier

Target Site

gRNA Name DNA Strand Targeting Domain

Length Seq ID

CFTR-R553X-1 - GCUUUAUAUUCUGUUUC 17 466

CFTR-R553X-2 - GGUGGAAUCACACUGAG 17 456

CFTR-R553X-3 - GGAAUCACACUGAGUGG 17 457

CFTR-R553X-4 - GUUCAAAAUUUCAACUG 17 464

CFTR-R553X-5 - GGUGAAUAACUAAUUAU 17 465

CFTR-R553X-6 - GGGGUUUUAUGGCUAGU 17 458

CFTR-R553X-7 - GAGCAAGAAUUUCUUUAGCA 20 462

CFTR-R553X-8 - GACAAUAUAGUUCUUGGAGA 20 460

CFTR-R553X-9 - GAAGGUGGAAUCACACUGAG 20 461

CFTR-R553X-10 - GGUGGAAUCACACUGAGUGG 20 454

CFTR-R553X-11 - GAGAAAGACAAUAUAGUUCU 20 453

Table 25B provides exemplary targeting domains for correcting a mutation (e.g., R553X) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., R553X) and have a high level of orthogonality. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 25B

324

5535.1 CFTR-R553X-25 - AAUAUAGUUCUUGGAGAAGG 20 474

CFTR-R553X-26 - CUGGAAUUGAAAAAAUCCUG 20 479

CFTR-R553X-27 - CAAGGUGAAUAACUAAU UAU 20 475

CFTR-R553X-28 - CCUGGGGU UUUAUGGCUAGU 20 481

Table 25C provides exemplary targeting domains for correcting a mutation (e.g., R553X) in the CFTR gene selected according to the third tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., R553X) and start with a 5'G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 25C

Table 25D provides exemplary targeting domains for correcting a mutation (e.g., R553X) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., R553X). It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 25D

325

5535.1 CFTR-R553X-38 - AUUGCUUUAUAUUCUGUUUC 20 476

CFTR-R553X-39 - UCCUGGGGUUUUAUGGCUAG 20 480

CFTR-R553X-40 - AAUUUUCUAUUUUUGGUAAU 20 473

CFTR-R553X-41 + AUUGUCUUUCUCUGCAAACU 20 483

CFTR-R553X-42 - UCUGGAAUUGAAAAAAUCCU 20 478

CFTR-R553X-43 - ACUCUCUAAUU UUCUAU UUU 20 472

Table 26A provides exemplary targeting domains for correcting a mutation (e.g., R553X) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., R553X), have a high level of orthogonality, start with a 5'G, and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 26A

326

5535.1 54

CFTR-R553X-

- GGGGUUUUAUGGCUAGUGGGUU 22

55 1905

Table 26B provides exemplary targeting domains for correcting a mutation (e.g., R553X) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., R553X), have a high level of orthogonality and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 26B

327

5535.1 CFTR-R553X-

+ UAACCCACUAGCCAUAAAACCC 22

68 1917

CFTR-R553X-

+ U UAACCCACUAGCCAUAAAACCC 23

69 1918

CFTR-R553X-

+ CUUAACCCACUAGCCAUAAAACCC 24

70 1919

CFTR-R553X-

+ ACUUUUAGUAUGCUCAAU 18

71 1920

CFTR-R553X-

+ CACUUUUAGUAUGCUCAAU 19

72 1921

CFTR-R553X-

+ UCACUUUUAGUAUGCUCAAU 20

73 756

CFTR-R553X-

+ AGUCACUUUUAGUAUGCUCAAU 22

74 1922

CFTR-R553X-

+ AGAGUCACUUUUAGUAUGCUCAAU 24

75 1923

CFTR-R553X-

- UGGAGAAGGUGGAAUCACA 19

76 2163

CFTR-R553X-

- UUGGAGAAGGUGGAAUCACA 20

77 742

CFTR-R553X-

- CUUGGAGAAGGUGGAAUCACA 21

78 2164

CFTR-R553X-

- UCU UGGAGAAGGUGGAAUCACA 22

79 2165

CFTR-R553X-

- UUCUUGGAGAAGGUGGAAUCACA 23

80 2166

CFTR-R553X-

- CCUGGGGU UUUAUGGCUA 18

81 1924

CFTR-R553X-

- UCCUGGGGUUUUAUGGCUA 19

82 1925

CFTR-R553X-

- AUCCUGGGGUUUUAUGGCUA 20

83 750

CFTR-R553X-

- AAUCCUGGGGUUUUAUGGCUA 21

84 1926

CFTR-R553X-

- AAAUCCUGGGGUUUUAUGGCUA 22

85 1927

CFTR-R553X-

- AAAAUCCUGGGGUUUUAUGGCUA 23

86 1928

CFTR-R553X-

- AAAAAUCCUGGGGUUUUAUGGCUA 24

87 1929

CFTR-R553X-

- UGCUUUAUAUUCUGUUUC 18

88 1931

CFTR-R553X- - UUGCUUUAUAUUCUGU UUC 19 1932

328

5535.1 89

CFTR-R553X-

- AUUGCUUUAUAUUCUGUUUC 20

38 476

CFTR-R553X-

- UAUUGCUUUAUAUUCUGUUUC 21

90 1933

CFTR-R553X-

- CUAUUGCUUUAUAUUCUGUUUC 22

91 1934

CFTR-R553X-

- UCUAUUGCUUUAUAUUCUGUUUC 23

92 1935

CFTR-R553X-

- CUCUAUUGCUUUAUAU UCUGUUUC 24

93 1936

CFTR-R553X-

- AAGAAUUUCUUUAGCAAG 18

94 1937

CFTR-R553X-

- CAAGAAUUUCUUUAGCAAG 19

95 1938

CFTR-R553X-

- UAUAGUUCUUGGAGAAGG 18

96 2167

CFTR-R553X-

- AUAUAGUUCUUGGAGAAGG 19

97 2168

CFTR-R553X-

- AAUAUAGUUCUUGGAGAAGG 20

25 474

CFTR-R553X-

- CAAUAUAGUUCUUGGAGAAGG 21

98 2169

CFTR-R553X-

- ACAAUAUAGUUCUUGGAGAAGG 22

99 2170

CFTR-R553X-

- AGACAAUAUAGUUCUUGGAGAAGG 24

100 2171

CFTR-R553X-

- UU UUAUGGCUAGUGGGUU 18

101 1942

CFTR-R553X-

- UGGGGUUUUAUGGCUAGUGGGUU 23

102 1943

CFTR-R553X-

- CUGGGGUUUUAUGGCUAGUGGGUU 24

103 1944

Table 26C provides exemplary targeting domains for correcting a mutation (e.g., R553X) in the CFTR gene selected according to the third tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., R553X), start with a 5'G and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with

329

5535.1 a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 26C

Table 26D provides exemplary targeting domains for correcting a mutation (e.g., R553X) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., R553X), and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through

complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 26D

330

5535.1 CFTR-R553X-

+ CU AU U ACCAAAAAU AG AAAAU U A 23

114 1954

CFTR-R553X-

+ CCU AU U ACCAAAAAU AG AAAAU U A 24

115 1955

CFTR-R553X-

+ AAAUGUCUGUAAUUUUUUUAC 21

116 1956

CFTR-R553X-

+ AGAAAUGUCUGUAAUU UUUUUAC 23

117 1957

CFTR-R553X-

- CUGGAAUUGAAAAAAUCC 18

118 1964

CFTR-R553X-

- UCUGGAAUUGAAAAAAUCC 19

119 1965

CFTR-R553X-

- UUCUGGAAUUGAAAAAAUCC 20

24 477

CFTR-R553X-

- UUUCUGGAAUUGAAAAAAUCC 21

120 1966

CFTR-R553X-

- UGUUUCUGGAAUUGAAAAAAUCC 23

121 1967

CFTR-R553X-

- CUGUUUCUGGAAUUGAAAAAAUCC 24

122 1968

CFTR-R553X-

- UGAGUGGAGGUCAAUGAGC 19

123 2983

CFTR-R553X-

- CUGAGUGGAGGUCAAUGAGC 20

124 2984

CFTR-R553X-

- ACUGAGUGGAGGUCAAUGAGC 21

125 2985

CFTR-R553X-

- CACUGAGUGGAGGUCAAUGAGC 22

126 2986

CFTR-R553X-

- ACACUGAGUGGAGGUCAAUGAGC 23

127 2987

CFTR-R553X-

- CACACUGAGUGGAGGUCAAUGAGC 24

128 2988

CFTR-R553X-

- AGCAAGAAUUUCUUUAGCAAG 21

129 1939

CFTR-R553X-

- UGAGCAAGAAUUUCUUUAGCAAG 23

130 2989

CFTR-R553X-

- AUGAGCAAGAAUUUCU UUAGCAAG 24

131 2990

Table 26E provides exemplary targeting domains for correcting a mutation (e.g., R553X) in the CFTR gene selected according to the fifth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., R553X), and PAM is NNGRRV. It is contemplated herein

331

5535.1 that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with ; aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 26E

332

5535.1 148

CFTR-R553X-

+ G A A AC AG A A U A U A A AG C A A U A 21

149 1999

CFTR-R553X-

+ AGAAACAGAAUAUAAAGCAAUA 22

150 2000

CFTR-R553X-

+ C AG A A AC AG A A U A U A A AG C A A U A 23

151 2001

CFTR-R553X-

+ CCAGAAACAGAAUAUAAAGCAAUA 24

152 2002

CFTR-R553X-

+ UAGUUAUUCACCUUGCUA 18

153 2003

CFTR-R553X-

+ UUAGUUAUUCACCUUGCUA 19

154 2004

CFTR-R553X-

+ AUUAGUUAUUCACCUUGCUA 20

155 762

CFTR-R553X-

+ AAUUAGUUAUUCACCU UGCUA 21

156 2005

CFTR-R553X-

+ UAAUUAGUUAUUCACCUUGCUA 22

157 2006

CFTR-R553X-

+ AUAAUUAGUUAUUCACCUUGCUA 23

158 2007

CFTR-R553X-

+ AAUAAUUAGUUAUUCACCUUGCUA 24

159 2008

CFTR-R553X-

+ UUGUCUUUCUCUGCAAAC 18

160 2009

CFTR-R553X-

+ AUUGUCUUUCUCUGCAAAC 19

161 2010

CFTR-R553X-

+ UAUUGUCUUUCUCUGCAAAC 20

162 760

CFTR-R553X-

+ AUAUUGUCUUUCUCUGCAAAC 21

163 2011

CFTR-R553X-

+ UAUAUUGUCUUUCUCUGCAAAC 22

164 2012

CFTR-R553X-

+ CUAUAUUGUCU UUCUCUGCAAAC 23

165 2013

CFTR-R553X-

+ ACUAUAUUGUCUUUCUCUGCAAAC 24

166 2014

CFTR-R553X-

+ UGUGAUUCCACCUUCUCC 18

167 2179

CFTR-R553X-

+ GUGUGAUUCCACCUUCUCC 19

168 2180

CFTR-R553X-

+ AGUGUGAUUCCACCUUCUCC 20

169 761

333

5535.1 CFTR-R553X-

+ CAGUGUGAUUCCACCUUCUCC 21

170 2181

CFTR-R553X-

+ UCAGUGUGAUUCCACCU UCUCC 22

171 2182

CFTR-R553X-

+ CUCAGUGUGAUUCCACCUUCUCC 23

172 2183

CFTR-R553X-

+ ACUCAGUGUGAUUCCACCUUCUCC 24

173 2184

CFTR-R553X-

+ CCAGGAUUUUU UCAAU UC 18

174 2015

CFTR-R553X-

+ CCCAGGAUUU UUUCAAU UC 19

175 2016

CFTR-R553X-

+ CCCCAGGAU UUUUUCAAUUC 20

176 767

CFTR-R553X-

+ ACCCCAGGAUUUUUUCAAUUC 21

177 2017

CFTR-R553X-

+ AACCCCAGGAUUUUUUCAAUUC 22

178 2018

CFTR-R553X-

+ AAACCCCAGG AU UUUUUCAAUUC 23

179 2019

CFTR-R553X-

+ AAAACCCCAGG AU U U U U U CAAU U C 24

180 2020

CFTR-R553X-

+ CUAUUGCUUUAACCACAG 18

181 2021

CFTR-R553X-

+ ACUAUUGCUUUAACCACAG 19

182 2022

CFTR-R553X-

+ CACUAUUGCUUUAACCACAG 20

183 754

CFTR-R553X-

+ ACACUAUUGCUU UAACCACAG 21

184 2023

CFTR-R553X-

+ CACACUAUUGCUUUAACCACAG 22

185 2024

CFTR-R553X-

+ U CACACU AU UG CU U U AACCACAG 23

186 2025

CFTR-R553X-

+ AUCACACUAUUGCUUUAACCACAG 24

187 2026

CFTR-R553X-

+ U U ACCAAAAAU AG AAAAU 18

188 2027

CFTR-R553X-

+ AUUACCAAAAAUAGAAAAU 19

189 2028

CFTR-R553X-

+ UAU U ACCAAAAAU AGAAAAU 20

190 758

CFTR-R553X- + CU AU U ACCAAAAAU AG AAAAU 21 2029

334

5535.1 191

CFTR-R553X-

+ CCU AUU ACCAAAAAU AGAAAAU 22

192 2030

CFTR-R553X-

+ UCCUAUUACCAAAAAUAGAAAAU 23

193 2031

CFTR-R553X-

+ G U CCU AU U ACCAAAAAU AG AAAAU 24

194 2032

CFTR-R553X-

+ AGUAUGCUCAAUCUGAAU 18

195 2033

CFTR-R553X-

+ UAGUAUGCUCAAUCUGAAU 19

196 2034

CFTR-R553X-

+ U UAGUAUGCUCAAUCUGAAU 20

197 755

CFTR-R553X-

+ U UUAGUAUGCUCAAUCUGAAU 21

198 2035

CFTR-R553X-

+ U UUUAGUAUGCUCAAUCUGAAU 22

199 2036

CFTR-R553X-

+ CUU UUAGUAUGCUCAAUCUGAAU 23

200 2037

CFTR-R553X-

+ ACUUUUAGUAUGCUCAAUCUGAAU 24

201 2038

CFTR-R553X-

+ UGUCUUUCUCUGCAAACU 18

202 2039

CFTR-R553X-

+ UUGUCUUUCUCUGCAAACU 19

203 2040

CFTR-R553X-

+ AUUGUCUUUCUCUGCAAACU 20

41 483

CFTR-R553X-

+ UAUUGUCUUUCUCUGCAAACU 21

204 2041

CFTR-R553X-

+ AUAUUGUCUUUCUCUGCAAACU 22

205 2042

CFTR-R553X-

+ UAUAUUGUCUUUCUCUGCAAACU 23

206 2043

CFTR-R553X-

+ CUAUAUUGUCU UUCUCUGCAAACU 24

207 2044

CFTR-R553X-

+ U U AACCACAG UUGAAAU U 18

208 2045

CFTR-R553X-

+ U U U AACCACAG UUGAAAU U 19

209 2046

CFTR-R553X-

+ CUUU AACCACAG UUGAAAU U 20

210 753

CFTR-R553X-

+ G CU U U AACCACAG UUGAAAU U 21

211 2047

335

5535.1 CFTR-R553X-

+ UGCUUUAACCACAGUUGAAAUU 22

212 2048

CFTR-R553X-

+ U UGCUUUAACCACAGUUGAAAUU 23

213 2049

CFTR-R553X-

+ AU UG CU U U AACCACAG U UG AAAU U 24

214 2050

CFTR-R553X-

- UAUAUUCUGUUUCUGGAA 18

215 2051

CFTR-R553X-

- UUAUAUUCUGUUUCUGGAA 19

216 2052

CFTR-R553X-

- UU UAUAUUCUGUUUCUGGAA 20

217 748

CFTR-R553X-

- CUUUAUAUUCUGUUUCUGGAA 21

218 2053

CFTR-R553X-

- GCUU UAUAUUCUGUUUCUGGAA 22

219 2054

CFTR-R553X-

- UGCU UUAUAUUCUGUU UCUGGAA 23

220 2055

CFTR-R553X-

- UUGCUUUAUAUUCUGU UUCUGGAA 24

221 2056

CFTR-R553X-

- AUUUUCUAUUU UUGGUAA 18

222 2059

CFTR-R553X-

- AAUUUUCUAUUUUUGGUAA 19

223 2060

CFTR-R553X-

- UAAUUUUCUAUUUUUGGUAA 20

224 736

CFTR-R553X-

- CUAAUUUUCUAU UUUUGGUAA 21

225 2061

CFTR-R553X-

- UCUAAUUUUCUAUUUUUGGUAA 22

226 2062

CFTR-R553X-

- CUCUAAUUUUCUAUUUUUGGUAA 23

227 2063

CFTR-R553X-

- UCUCUAAUUUUCUAUUUUUGGUAA 24

228 2064

CFTR-R553X-

- GACAUCUCCAAGUUUGCA 18

229 2065

CFTR-R553X-

- GGACAUCUCCAAGUUUGCA 19

230 2066

CFTR-R553X-

- AGGACAUCUCCAAGUUUGCA 20

231 738

CFTR-R553X-

- UAGGACAUCUCCAAGUU UGCA 21

232 2067

CFTR-R553X- - AUAGGACAUCUCCAAGU UUGCA 22 2068

336

5535.1 233

CFTR-R553X-

- AAUAGGACAUCUCCAAGUUUGCA 23

234 2069

CFTR-R553X-

- UAAUAGGACAUCUCCAAGUUUGCA 24

235 2070

CFTR-R553X-

- CACACUGAGUGGAGGUCA 18

236 2071

CFTR-R553X-

- UCACACUGAGUGGAGGUCA 19

237 2072

CFTR-R553X-

- AUCACACUGAGUGGAGGUCA 20

238 744

CFTR-R553X-

- AAUCACACUGAGUGGAGGUCA 21

239 2073

CFTR-R553X-

- GAAUCACACUGAGUGGAGGUCA 22

240 2074

CFTR-R553X-

- GGAAUCACACUGAGUGGAGGUCA 23

241 2075

CFTR-R553X-

- UGGAAUCACACUGAGUGGAGGUCA 24

242 2076

CFTR-R553X-

- GUGCCU UUCAAAUUCAGA 18

243 2077

CFTR-R553X-

- UGUGCCUUUCAAAUUCAGA 19

244 2078

CFTR-R553X-

- AUGUGCCUU UCAAAUUCAGA 20

245 735

CFTR-R553X-

- GAUGUGCCUU UCAAAU UCAGA 21

246 2079

CFTR-R553X-

- AGAUGUGCCUUUCAAAUUCAGA 22

247 2080

CFTR-R553X-

- AAGAUGUGCCUUUCAAAUUCAGA 23

248 2081

CFTR-R553X-

- GAAGAUGUGCCUUUCAAAUUCAGA 24

249 2082

CFTR-R553X-

- AUAUAUGAUUACAUUAGA 18

250 2083

CFTR-R553X-

- GAUAUAUGAUUACAUUAGA 19

251 2084

CFTR-R553X-

- UGAUAUAUGAUUACAUUAGA 20

22 471

CFTR-R553X-

- GUGAUAUAUGAUUACAUUAGA 21

252 2085

CFTR-R553X-

- UGUGAUAUAUGAUUACAUUAGA 22

253 2086

337

5535.1 CFTR-R553X-

- GUGUGAUAUAUGAUUACAUUAGA 23

254 2087

CFTR-R553X-

- AGUGUGAUAUAUGAUUACAUUAGA 24

255 2088

CFTR-R553X-

- AAGGUGGAAUCACACUGA 18

256 2089

CFTR-R553X-

- GAAGGUGGAAUCACACUGA 19

257 2090

CFTR-R553X-

- AGAAGGUGGAAUCACACUGA 20

258 743

CFTR-R553X-

- GAGAAGGUGGAAUCACACUGA 21

259 2091

CFTR-R553X-

- GGAGAAGGUGGAAUCACACUGA 22

260 2192

CFTR-R553X-

- UGGAGAAGGUGGAAUCACACUGA 23

261 2193

CFTR-R553X-

- UUGGAGAAGGUGGAAUCACACUGA 24

262 2194

CFTR-R553X-

- UCUGGAAUUGAAAAAAUC 18

263 2098

CFTR-R553X-

- UUCUGGAAUUGAAAAAAUC 19

264 2099

CFTR-R553X-

- UUUCUGGAAUUGAAAAAAUC 20

265 749

CFTR-R553X-

- GU UUCUGGAAUUGAAAAAAUC 21

266 2100

CFTR-R553X-

- UGUUUCUGGAAUUGAAAAAAUC 22

267 2101

CFTR-R553X-

- CUGU UUCUGGAAUUGAAAAAAUC 23

268 2102

CFTR-R553X-

- UCUGUUUCUGGAAUUGAAAAAAUC 24

269 2103

CFTR-R553X-

- AG AAAG ACAAU AU AG U U C 18

270 2195

CFTR-R553X-

- G AG AAAG ACAAU AU AG U U C 19

271 2196

CFTR-R553X-

- AG AG AAAG ACAAU AU AG U U C 20

272 739

CFTR-R553X-

- CAGAGAAAGACAAUAUAGUUC 21

273 2197

CFTR-R553X-

- GCAG AG AAAG ACAAU AU AG U U C 22

274 2198

CFTR-R553X- - UGCAGAGAAAGACAAUAUAGUUC 23 2199

338

5535.1 275

CFTR-R553X-

- U UG CAG AG AAAG ACAAU AU AG U U C 24

276 2200

CFTR-R553X-

- AUAUAGUUCUUGGAGAAG 18

277 2201

CFTR-R553X-

- AAUAUAGUUCUUGGAGAAG 19

278 2202

CFTR-R553X-

- CAAUAUAGUUCUUGGAGAAG 20

279 741

CFTR-R553X-

- ACAAUAUAGUUCUUGGAGAAG 21

280 2203

CFTR-R553X-

- GACAAUAUAGUUCUUGGAGAAG 22

281 2204

CFTR-R553X-

- AGACAAUAUAGUUCUUGGAGAAG 23

282 2205

CFTR-R553X-

- AAGACAAUAUAGUUCUUGGAGAAG 24

283 2206

CFTR-R553X-

- AGGUGGAAUCACACUGAG 18

284 2111

CFTR-R553X-

- AAGGUGGAAUCACACUGAG 19

285 2112

CFTR-R553X-9 - GAAGGUGGAAUCACACUGAG 20 461

CFTR-R553X-

- AGAAGGUGGAAUCACACUGAG 21

286 2113

CFTR-R553X-

- GAGAAGGUGGAAUCACACUGAG 22

287 2114

CFTR-R553X-

- GGAGAAGGUGGAAUCACACUGAG 23

288 2207

CFTR-R553X-

- UGGAGAAGGUGGAAUCACACUGAG 24

289 2208

CFTR-R553X-

- GAUAUAUGAUUACAUUAG 18

290 2117

CFTR-R553X-

- UGAUAUAUGAUUACAU UAG 19

291 2118

CFTR-R553X-

- GUGAUAUAUGAUUACAUUAG 20

292 734

CFTR-R553X-

- UGUGAUAUAUGAUUACAUUAG 21

293 2119

CFTR-R553X-

- GUGUGAUAUAUGAUUACAUUAG 22

294 2120

CFTR-R553X-

- AGUGUGAUAUAUGAUUACAUUAG 23

295 2121

339

5535.1 CFTR-R553X-

- UAGUGUGAUAUAUGAUUACAUUAG 24

296 2122

CFTR-R553X-

- AAGACAAUAUAGUUCUUG 18

297 2209

CFTR-R553X-

- AAAG ACAAU AU AG U U CU UG 19

298 2210

CFTR-R553X-

- GAAAGACAAUAUAGUUCUUG 20

299 740

CFTR-R553X-

- AG AAAG ACAAU AU AG U U CU UG 21

300 2211

CFTR-R553X-

- GAG AAAG ACAAU AU AG U U CU UG 22

301 2212

CFTR-R553X-

- AGAGAAAGACAAUAUAGUUCUUG 23

302 2213

CFTR-R553X-

- CAGAGAAAGACAAUAUAGUUCUUG 24

303 2214

CFTR-R553X-

- AGGACAUCUCCAAGUUUG 18

304 2123

CFTR-R553X-

- UAGGACAUCUCCAAGUU UG 19

305 2124

CFTR-R553X-

- AUAGGACAUCUCCAAGU UUG 20

306 737

CFTR-R553X-

- AAUAGGACAUCUCCAAGUUUG 21

307 2125

CFTR-R553X-

- UAAUAGGACAUCUCCAAGUUUG 22

308 2126

CFTR-R553X-

- GU AAUAGGACAUCUCCAAGUUUG 23

309 2127

CFTR-R553X-

- GGUAAUAGGACAUCUCCAAGUUUG 24

310 2128

CFTR-R553X-

- UGUGAUAUAUGAUUACAU 18

311 2129

CFTR-R553X-

- GUGUGAUAUAUGAUUACAU 19

312 2130

CFTR-R553X-

- AGUGUGAUAUAUGAUUACAU 20

313 733

CFTR-R553X-

- UAGUGUGAUAUAUGAU UACAU 21

314 2131

CFTR-R553X-

- AUAGUGUGAUAUAUGAUUACAU 22

315 2132

CFTR-R553X-

- AAUAGUGUGAUAUAUGAUUACAU 23

316 2133

CFTR-R553X- - CAAUAGUGUGAUAUAUGAUUACAU 24 2134

340

5535.1 317

CFTR-R553X-

- GAAAGACAAUAUAGUUCU 18

318 2135

CFTR-R553X-

- AG AAAG ACAAU AU AG U U CU 19

319 2136

CFTR-R553X-

- GAGAAAGACAAUAUAGUUCU 20

11 453

CFTR-R553X-

- AG AG AAAG ACAAU AU AG U U CU 21

320 2137

CFTR-R553X-

- CAGAGAAAGACAAUAUAGUUCU 22

321 2138

CFTR-R553X-

- GCAG AG AAAG ACAAU AU AG U U CU 23

322 2139

CFTR-R553X-

- UGCAGAGAAAGACAAUAUAGUUCU 24

323 2140

CFTR-R553X-

- GGGU UAAGAAUCACAU UU 18

324 2215

CFTR-R553X-

- UGGGUUAAGAAUCACAUUU 19

325 2216

CFTR-R553X-

- GUGGGUUAAGAAUCACAUUU 20

326 752

CFTR-R553X-

- AGUGGGUUAAGAAUCACAUUU 21

327 2217

CFTR-R553X-

- UAGUGGGUUAAGAAUCACAUUU 22

328 2218

CFTR-R553X-

- CUAGUGGGUUAAGAAUCACAUUU 23

329 2219

CFTR-R553X-

- GCUAGUGGGUUAAGAAUCACAUUU 24

330 2220

CFTR-R553X-

- UUGCUUUAUAUUCUGU UU 18

331 2148

CFTR-R553X-

- AUUGCUUUAUAUUCUGUUU 19

332 2149

CFTR-R553X-

- UAUUGCUUUAUAUUCUGUUU 20

333 747

CFTR-R553X-

- CUAUUGCUU UAUAUUCUGUUU 21

334 2150

CFTR-R553X-

- UCUAUUGCU UUAUAUUCUGUUU 22

335 2151

CFTR-R553X-

- CUCUAUUGCUUUAUAUUCUGUUU 23

336 2152

CFTR-R553X-

- UCUCUAUUGCUUUAUAUUCUGUUU 24

337 2153

341

5535.1 Table 27 A provides exemplary targeting domains for correcting a mutation (e.g., R553X) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., R553X), have a high level of orthogonality and start with a 5'G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 27

Table 27B provides exemplary targeting domains for correcting a mutation (e.g., R553X) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., R553X) and have a high level of orthogonality. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 27B

342

5535.1 CFTR-R553X-

+ AAUGUAAUCAUAUAUCACAC 20

344 2156

CFTR-R553X-

+ AACCCACUAGCCAUAAAACC 20

345 930

CFTR-R553X-

+ ACAUGAAUGACAUUUACAGC 20

346 2157

Table 27C provides exemplary targeting domains for correcting a mutation (e.g., R553X) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., R553X). It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 27C

Table 28A provides exemplary targeting domains for correcting a mutation (e.g., W1282X) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., W1282X), have a high level of orthogonality and start with a 5'G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting

343

5535.1 domains in the Table lean be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 28A

Table 28B provides exemplary targeting domains for correcting a mutation (e.g.,

W1282X) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., W1282X) and have a high level of orthogonality. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table lean be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 28B

344

5535.1 CFTR-W1282X-

+ CUAUAAGGUAAAAGUGA 17

11 3003

CFTR-W1282X-

- UAACUUUGCAACAGUGA 17

12 3004

CFTR-W1282X-

+ CAAGAGGCCCACCUAUA 17

13 3005

CFTR-W1282X-

- CUUUGGAGUGAUACCAC 17

14 3006

CFTR-W1282X-

+ CUAUGAGAAAACUGCAC 17

15 3007

CFTR-W1282X-

+ AAGACACACCAUCGAUC 17

16 3008

CFTR-W1282X-

- UUGGGAAGAACUGGAUC 17

17 3009

CFTR-W1282X-

+ AUCCAGUUCUUCCCAAG 17

18 3010

CFTR-W1282X-

- CACUUUUACCUUAUAGG 17

19 3011

CFTR-W1282X-

- CAGUGCAGUUUUCUCAU 17

20 3012

CFTR-W1282X-

+ UAUAAGGUAAAAGUGAU 17

21 3013

CFTR-W1282X-

+ UCACUUCUGUGACAUAU 17

22 3014

CFTR-W1282X-

- CAUCACUUUUACCUUAU 17

23 3015

CFTR-W1282X-

- CUUAUAGGUGGGCCUCU 17

24 3016

CFTR-W1282X-

- AGAUCGAUGGUGUGUCU 17

25 3017

CFTR-W1282X-

- ACUUUUACCUUAUAGGU 17

26 3018

CFTR-W1282X-

- UUAUAGGUGGGCCUCUU 17

27 3019

CFTR-W1282X-

- AAAGGACUUAGCCAGAAAAA 20

28 3020

CFTR-W1282X-

+ CACCUGUGGUAUCACUCCAA 20

29 3021

CFTR-W1282X-

- ACUGAAUUAUGUUUAUGGCA 20

30 3022

CFTR-W1282X-

- UCUUGGGAAGAACUGGAUCA 20

31 3023

CFTR-W1282X- - UUGAGACUACUGAACACUGA 20 3024

345

5535.1 32

CFTR-W1282X-

+ CACCUAUAAGGUAAAAGUGA 20

33 3025

CFTR-W1282X-

+ UCCCAAGAGGCCCACCUAUA 20

34 3026

CFTR-W1282X-

- ACAAUACUGAAUUAUGUUUA 20

35 3027

CFTR-W1282X-

- AGCCUU UGGAGUGAUACCAC 20

36 3028

CFTR-W1282X-

+ UGCCUAUGAGAAAACUGCAC 20

37 3029

CFTR-W1282X-

+ CCCAAGACACACCAUCGAUC 20

38 3030

CFTR-W1282X-

- CUCUUGGGAAGAACUGGAUC 20

39 3031

CFTR-W1282X-

+ UAAUUUAGUUGCCUUU UUUC 20

40 3032

CFTR-W1282X-

+ CUGAUCCAGUUCUUCCCAAG 20

41 3033

CFTR-W1282X-

- CAUCACUUUUACCUUAUAGG 20

42 3034

CFTR-W1282X-

+ UAAGUCCUUUUGCUCACCUG 20

43 3035

CFTR-W1282X-

- CUCCAGUGCAGUUUUCUCAU 20

44 3036

CFTR-W1282X-

+ ACCUAUAAGGUAAAAGUGAU 20

45 3037

CFTR-W1282X-

- UCCCAUCACU UUUACCU UAU 20

46 3038

CFTR-W1282X-

- UACCU UAUAGGUGGGCCUCU 20

47 3039

CFTR-W1282X-

- UCCAGAUCGAUGGUGUGUCU 20

48 3040

CFTR-W1282X-

- AUCACUUUUACCUUAUAGGU 20

49 3041

CFTR-W1282X-

- CCAGAUCGAUGGUGUGUCUU 20

50 3042

Table 28C provides exemplary targeting domains for correcting a mutation (e.g., W1282X) in the CFTR gene selected according to the third tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., W1282X) and start with a 5'G. It is

346

5535.1 contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table lean be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 28C

Table 28D provides exemplary targeting domains for correcting a mutation (e.g., W1282X) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., W1282X). It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table lean be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 28D

347

5535.1 59

CFTR-W1282X-

- ACCUUAUAGGUGGGCCUCUU 20

60 3052

Table 29A provides exemplary targeting domains for correcting a mutation (e.g., W1282X) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., W1282X), have a high level of orthogonality, start with a 5'G, and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table lean be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 29A

Table 29B provides exemplary targeting domains for correcting a mutation (e.g., W1282X) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., W1282X), have a high level of orthogonality and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain

348

5535.1 hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table lean be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 29B

349

5535.1 CFTR-

+ AUCCCAAGACACACCAUCGAU 21

W1282X-86 3078

CFTR-

+ AAUCCCAAGACACACCAUCGAU 22

W1282X-87 3079

CFTR-

+ UGAAUCCCAAGACACACCAUCGAU 24

W1282X-88 3080

CFTR-

- UGGGCCUCU UGGGAAGAA 18

W1282X-89 3081

CFTR-

- AGGUGGGCCUCUUGGGAAGAA 21

W1282X-90 3082

CFTR-

- UAGGUGGGCCUCUUGGGAAGAA 22

W1282X-91 3083

CFTR-

- AUAGGUGGGCCUCUUGGGAAGAA 23

W1282X-92 3084

CFTR-

- UAUAGGUGGGCCUCUUGGGAAGAA 24

W1282X-93 3085

CFTR-

- UGGGAAGAACUGGAUCAGGG 20

W1282X-94 3086

CFTR-

- UUGGGAAGAACUGGAUCAGGG 21

W1282X-95 3087

CFTR-

- CUUGGGAAGAACUGGAUCAGGG 22

W1282X-96 3088

CFTR-

- UCUUGGGAAGAACUGGAUCAGGG 23

W1282X-97 3089

CFTR-

- CUCUUGGGAAGAACUGGAUCAGGG 24

W1282X-98 3090

CFTR-

- CAGAUCGAUGGUGUGUCU 18

W1282X-99 3091

CFTR-

- CCAGAUCGAUGGUGUGUCU 19

W1282X-100 3092

CFTR-

- UCCAGAUCGAUGGUGUGUCU 20

W1282X-48 3040

CFTR-

- AUCCAGAUCGAUGGUGUGUCU 21

W1282X-101 3093

CFTR-

- AAUCCAGAUCGAUGGUGUGUCU 22

W1282X-102 3094

CFTR-

- AAAUCCAGAUCGAUGGUGUGUCU 23

W1282X-103 3095

Table 29C provides exemplary targeting domains for correcting a mutation (e.g., W1282X) in the CFTR gene selected according to the third tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., W1282X), start with a 5'G and PAM is

350

5535.1 NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table lean be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 29C

Table 29D provides exemplary targeting domains for correcting a mutation (e.g., W1282X) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., W1282X), and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table lean be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 29D

351

5535.1 CFTR-

+ UUUCCUUCACUGUUGCAAAGUUA 23

W1282X-112 3104

CFTR-

+ CUUUCCUUCACUGUUGCAAAGUUA 24

W1282X-113 3105

CFTR-

+ CAG AG U AAU AUG AAU U U C 18

W1282X-114 3106

CFTR-

+ UGCAGAGUAAUAUGAAUUUC 20

W1282X-115 3107

CFTR-

+ AUGCAUAACAAAUAUAUUUUG 21

W1282X-116 3108

CFTR-

+ AAUGCAUAACAAAUAUAUUUUG 22

W1282X-117 3109

CFTR-

+ CAAUG CAU AACAAAU AU AU U U UG 23

W1282X-118 3110

CFTR-

+ AAAU AU AU U U UG CAG AG U AAU 21

W1282X-119 3111

CFTR-

+ CAAAUAUAUUUUGCAGAGUAAU 22

W1282X-120 3112

CFTR-

+ ACAAAU AU AU U U UG CAG AG U AAU 23

W1282X-121 3113

CFTR-

+ AACAAAU AU AU U U UGCAG AG U AAU 24

W1282X-122 3114

CFTR-

- ACAGUGAAGGAAAGCCUU 18

W1282X-123 3115

CFTR-

- AACAG UGAAGGAAAG CC U U 19

W1282X-124 3116

CFTR-

- CAACAGUGAAGGAAAGCCUU 20

W1282X-59 3051

CFTR-

- U G CAACAG UGAAGGAAAG CC U U 22

W1282X-125 3117

CFTR-

- U U G CAACAG U G AAG G AA AG CCU U 23

W1282X-126 3118

CFTR-

- UUUGCAACAGUGAAGG A A AG C C U U 24

W1282X-127 3119

Table 29E provides exemplary targeting domains for correcting a mutation (e.g., W1282X) in the CFTR gene selected according to the fifth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., W1282X), and PAM is NNGRRV. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table lean be used

352

5535.1 with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 29E

353

5535.1 CFTR-

+ CUUCCCUGAUCCAGUUCUUCCC 22

W1282X-145 3137

CFTR-

+ UCUUCCCUGAUCCAGUUCUUCCC 23

W1282X-146 3138

CFTR-

+ CUCUUCCCUGAUCCAGUUCUUCCC 24

W1282X-147 3139

CFTR-

+ UAUGAGAAAACUGCACUG 18

W1282X-148 3140

CFTR-

+ CUAUGAGAAAACUGCACUG 19

W1282X-149 3141

CFTR-

+ CCUAUGAGAAAACUGCACUG 20

W1282X-150 3142

CFTR-

+ GCCUAUGAGAAAACUGCACUG 21

W1282X-151 3143

CFTR-

+ UGCCUAUGAGAAAACUGCACUG 22

W1282X-152 3144

CFTR-

+ CUGCCUAUGAGAAAACUGCACUG 23

W1282X-153 3145

CFTR-

+ UCUGCCUAUGAGAAAACUGCACUG 24

W1282X-154 3146

CFTR-

+ ACCUAUAAGGUAAAAGUG 18

W1282X-155 3147

CFTR-

+ CACCUAUAAGGUAAAAGUG 19

W1282X-156 3148

CFTR-

+ CCACCUAUAAGGUAAAAGUG 20

W1282X-157 3149

CFTR-

+ CCCACCUAUAAGGUAAAAGUG 21

W1282X-158 3150

CFTR-

+ GCCCACCUAUAAGGUAAAAGUG 22

W1282X-159 3151

CFTR-

+ GGCCCACCUAUAAGGUAAAAGUG 23

W1282X-160 3152

CFTR-

+ AGGCCCACCUAUAAGGUAAAAGUG 24

W1282X-161 3153

CFTR-

+ GACAUCUUUUCUGCCUAU 18

W1282X-162 3154

CFTR-

+ AGACAUCUUUUCUGCCUAU 19

W1282X-163 3155

CFTR-

+ GAGACAUCUUUUCUGCCUAU 20

W1282X-164 3156

CFTR-

+ AGAGACAUCUUUUCUGCCUAU 21

W1282X-165 3157

354

5535.1 CFTR-

+ UAGAGACAUCUUUUCUGCCUAU 22

W1282X-166 3158

CFTR-

+ UUAGAGACAUCUUUUCUGCCUAU 23

W1282X-167 3159

CFTR-

+ UUUAGAGACAUCUUUUCUGCCUAU 24

W1282X-168 3160

CFTR-

+ GAGACAUCUUUUCUGCCU 18

W1282X-169 3161

CFTR-

+ AGAGACAUCUUUUCUGCCU 19

W1282X-170 3162

CFTR-

+ UAGAGACAUCUUUUCUGCCU 20

W1282X-171 3163

CFTR-

+ UUAGAGACAUCUUUUCUGCCU 21

W1282X-172 3164

CFTR-

+ UUUAGAGACAUCUUUUCUGCCU 22

W1282X-173 3165

CFTR-

+ UUUUAGAGACAUCUUUUCUGCCU 23

W1282X-174 3166

CFTR-

+ CUUUUAGAGACAUCUUUUCUGCCU 24

W1282X-175 3167

CFTR-

- GAUACCACAGGUGAGCAA 18

W1282X-176 3168

CFTR-

- UGAUACCACAGGUGAGCAA 19

W1282X-177 3169

CFTR-

- GUGAUACCACAGGUGAGCAA 20

W1282X-178 3170

CFTR-

- AGUGAUACCACAGGUGAGCAA 21

W1282X-179 3171

CFTR-

- GAGUGAUACCACAGGUGAGCAA 22

W1282X-180 3172

CFTR-

- GGAGUGAUACCACAGGUGAGCAA 23

W1282X-181 3173

CFTR-

- UGGAGUGAUACCACAGGUGAGCAA 24

W1282X-182 3174

CFTR-

- UUCAAUAACUUUGCAACA 18

W1282X-183 3175

CFTR-

- AUUCAAUAACUUUGCAACA 19

W1282X-184 3176

CFTR-

- GAUUCAAUAACUUUGCAACA 20

W1282X-185 3177

CFTR-

- GGAUUCAAUAACUUUGCAACA 21

W1282X-186 3178

355

5535.1 CFTR-

- GGGAUUCAAUAACUUUGCAACA 22

W1282X-187 3179

CFTR-

- UGGGAUUCAAUAACUUUGCAACA 23

W1282X-188 3180

CFTR-

- UUGGGAUUCAAUAACUUUGCAACA 24

W1282X-189 3181

CFTR-

- UUUUGAGACUACUGAACA 18

W1282X-190 3182

CFTR-

- UUUUUGAGACUACUGAACA 19

W1282X-191 3183

CFTR-

- UUUUUUGAGACUACUGAACA 20

W1282X-192 3184

CFTR-

- CUUUUUUGAGACUACUGAACA 21

W1282X-193 3185

CFTR-

- GCUUUUUUGAGACUACUGAACA 22

W1282X-194 3186

CFTR-

- AGCUUUUUUGAGACUACUGAACA 23

W1282X-195 3187

CFTR-

- CAGCUUUUUUGAGACUACUGAACA 24

W1282X-196 3188

CFTR-

- UUGGGAAGAACUGGAUCA 18

W1282X-197 3189

CFTR-

- CUUGGGAAGAACUGGAUCA 19

W1282X-198 3190

CFTR-

- UCUUGGGAAGAACUGGAUCA 20

W1282X-31 3023

CFTR-

- CUCUUGGGAAGAACUGGAUCA 21

W1282X-199 3191

CFTR-

- CCUCUUGGGAAGAACUGGAUCA 22

W1282X-200 3192

CFTR-

- GCCUCUUGGGAAGAACUGGAUCA 23

W1282X-201 3193

CFTR-

- GGCCUCUUGGGAAGAACUGGAUCA 24

W1282X-202 3194

CFTR-

- CAUGGUACCUAUAUGUCA 18

W1282X-203 3195

CFTR-

- GCAUGGUACCUAUAUGUCA 19

W1282X-204 3196

CFTR-

- GGCAUGGUACCUAUAUGUCA 20

W1282X-205 3197

CFTR-

- UGGCAUGGUACCUAUAUGUCA 21

W1282X-206 3198

356

5535.1 CFTR-

- AUGGCAUGGUACCUAUAUGUCA 22

W1282X-207 3199

CFTR-

- UAUGGCAUGGUACCUAUAUGUCA 23

W1282X-208 3200

CFTR-

- UUAUGGCAUGGUACCUAUAUGUCA 24

W1282X-209 3201

CFTR-

- GAGACUACUGAACACUGA 18

W1282X-210 3202

CFTR-

- UGAGACUACUGAACACUGA 19

W1282X-211 3203

CFTR-

- UUGAGACUACUGAACACUGA 20

W1282X-32 3024

CFTR-

- UUUGAGACUACUGAACACUGA 21

W1282X-212 3204

CFTR-

- UUUUGAGACUACUGAACACUGA 22

W1282X-213 3205

CFTR-

- UUUUUGAGACUACUGAACACUGA 23

W1282X-214 3206

CFTR-

- UUUUUUGAGACUACUGAACACUGA 24

W1282X-215 3207

CFTR-

- AUAACUUUGCAACAGUGA 18

W1282X-216 3208

CFTR-

- AAUAACUUUGCAACAGUGA 19

W1282X-217 3209

CFTR-

- CAAUAACUUUGCAACAGUGA 20

W1282X-58 3050

CFTR-

- UCAAUAACUUUGCAACAGUGA 21

W1282X-218 3210

CFTR-

- UUCAAUAACUUUGCAACAGUGA 22

W1282X-219 3211

CFTR-

- AU U CAAU AACU U UG CAACAG UG A 23

W1282X-220 3212

CFTR-

- GAUUCAAUAACUUUGCAACAGUGA 24

W1282X-221 3213

CFTR-

- UCAGCUUUUUUGAGACUA 18

W1282X-222 3214

CFTR-

- AUCAGCUUUUUUGAGACUA 19

W1282X-223 3215

CFTR-

- UAUCAGCUUUUUUGAGACUA 20

W1282X-224 3216

CFTR-

- UUAUCAGCUUUUUUGAGACUA 21

W1282X-225 3217

357

5535.1 CFTR-

- GU UAUCAGCUU UUUUGAGACUA 22

W1282X-226 3218

CFTR-

- UGUUAUCAGCU UUUUUGAGACUA 23

W1282X-227 3219

CFTR-

- UUGUUAUCAGCUUUUUUGAGACUA 24

W1282X-228 3220

CFTR-

- UGAGCAAAAGGACUUAGC 18

W1282X-229 3221

CFTR-

- G U G AG CAAAAG G AC U U AG C 19

W1282X-230 3222

CFTR-

- GGUGAGCAAAAGGACU UAGC 20

W1282X-231 3223

CFTR-

- AGGUGAGCAAAAGGACUUAGC 21

W1282X-232 3224

CFTR-

- CAG G U G AG CAAAAG G AC U U AG C 22

W1282X-233 3225

CFTR-

- ACAGG U G AG CAAAAG G AC U U AG C 23

W1282X-234 3226

CFTR-

- CACAGGUGAGCAAAAGGACUUAGC 24

W1282X-235 3227

CFTR-

- CUUGGGAAGAACUGGAUC 18

W1282X-236 3228

CFTR-

- UCU UGGGAAGAACUGGAUC 19

W1282X-237 3229

CFTR-

- CUCUUGGGAAGAACUGGAUC 20

W1282X-39 3031

CFTR-

- CCUCUUGGGAAGAACUGGAUC 21

W1282X-238 3230

CFTR-

- GCCUCUUGGGAAGAACUGGAUC 22

W1282X-239 3231

CFTR-

- GGCCUCUUGGGAAGAACUGGAUC 23

W1282X-240 3232

CFTR-

- GGGCCUCUUGGGAAGAACUGGAUC 24

W1282X-241 3233

CFTR-

- UAUUUGAUACUUGUACUC 18

W1282X-242 3234

CFTR-

- CUAUUUGAUACUUGUACUC 19

W1282X-243 3235

CFTR-

- GCUAUUUGAUACU UGUACUC 20

W1282X-244 3236

CFTR-

- UGCUAUUUGAUACUUGUACUC 21

W1282X-245 3237

358

5535.1 CFTR-

- CUGCUAUUUGAUACUUGUACUC 22

W1282X-246 3238

CFTR-

- ACUGCUAUUUGAUACU UGUACUC 23

W1282X-247 3239

CFTR-

- UACUGCUAUUUGAUACUUGUACUC 24

W1282X-248 3240

CFTR-

- ACCUUAUAGGUGGGCCUC 18

W1282X-249 3241

CFTR-

- UACCUUAUAGGUGGGCCUC 19

W1282X-250 3242

CFTR-

- UUACCUUAUAGGUGGGCCUC 20

W1282X-251 3243

CFTR-

- UU UACCUUAUAGGUGGGCCUC 21

W1282X-252 3244

CFTR-

- UU UUACCUUAUAGGUGGGCCUC 22

W1282X-253 3245

CFTR-

- CUUUUACCUUAUAGGUGGGCCUC 23

W1282X-254 3246

CFTR-

- ACUUUUACCUUAUAGGUGGGCCUC 24

W1282X-255 3247

CFTR-

- CCAGAUCGAUGGUGUGUC 18

W1282X-256 3248

CFTR-

- UCCAGAUCGAUGGUGUGUC 19

W1282X-257 3249

CFTR-

- AUCCAGAUCGAUGGUGUGUC 20

W1282X-258 3250

CFTR-

- AAUCCAGAUCGAUGGUGUGUC 21

W1282X-259 3251

CFTR-

- AAAUCCAGAUCGAUGGUGUGUC 22

W1282X-260 3252

CFTR-

- GAAAUCCAGAUCGAUGGUGUGUC 23

W1282X-261 3253

CFTR-

- AGAAAUCCAGAUCGAUGGUGUGUC 24

W1282X-262 3254

CFTR-

- GACUACUGAACACUGAAG 18

W1282X-263 3255

CFTR-

- AGACUACUGAACACUGAAG 19

W1282X-264 3256

CFTR-

- GAGACUACUGAACACUGAAG 20

W1282X-265 3257

CFTR-

- UGAGACUACUGAACACUGAAG 21

W1282X-266 3258

359

5535.1 CFTR-

- UUGAGACUACUGAACACUGAAG 22

W1282X-267 3259

CFTR-

- UUUGAGACUACUGAACACUGAAG 23

W1282X-268 3260

CFTR-

- UU UUGAGACUACUGAACACUGAAG 24

W1282X-269 3261

CFTR-

- UU UGGAGUGAUACCACAG 18

W1282X-270 3262

CFTR-

- CUU UGGAGUGAUACCACAG 19

W1282X-271 3263

CFTR-

- CCUUUGGAGUGAUACCACAG 20

W1282X-272 3264

CFTR-

- GCCUUUGGAGUGAUACCACAG 21

W1282X-273 3265

CFTR-

- AGCCUUUGGAGUGAUACCACAG 22

W1282X-274 3266

CFTR-

- AAGCCU UUGGAGUGAUACCACAG 23

W1282X-275 3267

CFTR-

- AAAGCCUUUGGAGUGAUACCACAG 24

W1282X-276 3268

CFTR-

- AUCACUUUUACCUUAUAG 18

W1282X-277 3269

CFTR-

- CAUCACUUUUACCUUAUAG 19

W1282X-278 3270

CFTR-

- CCAUCACU UUUACCUUAUAG 20

W1282X-279 3271

CFTR-

- CCCAUCACUUUUACCUUAUAG 21

W1282X-280 3272

CFTR-

- UCCCAUCACUUUUACCUUAUAG 22

W1282X-281 3273

CFTR-

- AUCCCAUCACUUUUACCUUAUAG 23

W1282X-282 3274

CFTR-

- GAUCCCAUCACUUUUACCUUAUAG 24

W1282X-283 3275

CFTR-

- GUGCAGUUUUCUCAUAGG 18

W1282X-284 3276

CFTR-

- AGUGCAGUUUUCUCAUAGG 19

W1282X-285 3277

CFTR-

- CAGUGCAGUUUUCUCAUAGG 20

W1282X-286 3278

CFTR-

- CCAGUGCAGUUUUCUCAUAGG 21

W1282X-287 3279

360

5535.1 CFTR-

- UCCAGUGCAGU UUUCUCAUAGG 22

W1282X-288 3280

CFTR-

- CUCCAGUGCAGUUUUCUCAUAGG 23

W1282X-289 3281

CFTR-

- UCUCCAGUGCAGUUUUCUCAUAGG 24

W1282X-290 3282

CFTR-

- AUAGGUGGGCCUCUUGGG 18

W1282X-291 3283

CFTR-

- UAUAGGUGGGCCUCUUGGG 19

W1282X-292 3284

CFTR-

- UUAUAGGUGGGCCUCU UGGG 20

W1282X-293 3285

CFTR-

- CUUAUAGGUGGGCCUCUUGGG 21

W1282X-294 3286

CFTR-

- CCUUAUAGGUGGGCCUCUUGGG 22

W1282X-295 3287

CFTR-

- ACCUUAUAGGUGGGCCUCUUGGG 23

W1282X-296 3288

CFTR-

- UACCU UAUAGGUGGGCCUCUUGGG 24

W1282X-297 3289

CFTR-

- UGAGACUACUGAACACUG 18

W1282X-298 3290

CFTR-

- UUGAGACUACUGAACACUG 19

W1282X-299 3291

CFTR-

- UU UGAGACUACUGAACACUG 20

W1282X-300 3292

CFTR-

- UU UUGAGACUACUGAACACUG 21

W1282X-301 3293

CFTR-

- UUUUUGAGACUACUGAACACUG 22

W1282X-302 3294

CFTR-

- UUUUUUGAGACUACUGAACACUG 23

W1282X-303 3295

CFTR-

- CUU UUUUGAGACUACUGAACACUG 24

W1282X-304 3296

CFTR-

- AAUAACUUUGCAACAGUG 18

W1282X-305 3297

CFTR-

- CAAUAACUUUGCAACAGUG 19

W1282X-306 3298

CFTR-

- UCAAUAACUUUGCAACAGUG 20

W1282X-307 3299

CFTR-

- UUCAAUAACUUUGCAACAGUG 21

W1282X-308 3300

361

5535.1 CFTR-

- AUUCAAUAACUUUGCAACAGUG 22

W1282X-309 3301

CFTR-

- G AU U CAAU AACU UUGCAACAGUG 23

W1282X-310 3302

CFTR-

- GGAUUCAAUAACUUUGCAACAGUG 24

W1282X-311 3303

CFTR-

- UCU UGGGAAGAACUGGAU 18

W1282X-312 3304

CFTR-

- CUCUUGGGAAGAACUGGAU 19

W1282X-313 3305

CFTR-

- CCUCUUGGGAAGAACUGGAU 20

W1282X-314 3306

CFTR-

- GCCUCU UGGGAAGAACUGGAU 21

W1282X-315 3307

CFTR-

- GGCCUCU UGGGAAGAACUGGAU 22

W1282X-316 3308

CFTR-

- GGGCCUCUUGGGAAGAACUGGAU 23

W1282X-317 3309

CFTR-

- UGGGCCUCU UGGGAAGAACUGGAU 24

W1282X-318 3310

CFTR-

- AACAGUGAAGG AAAG C C U 18

W1282X-319 3311

CFTR-

- CAACAGUGAAGGAAAGCCU 19

W1282X-320 3312

CFTR-

- GCAACAGUGAAGGAAAGCCU 20

W1282X-321 3313

CFTR-

- U G CAAC AG U G A AG G AAAG C C U 21

W1282X-322 3314

CFTR-

- UUGCAACAGUGAAGGAAAGCCU 22

W1282X-323 3315

CFTR-

- U U U G CAAC AG U G A AG G AAAG CC U 23

W1282X-324 3316

CFTR-

- C U U U G CAAC AG U G AAG G AAAG CC U 24

W1282X-325 3317

CFTR-

- CCUUAUAGGUGGGCCUCU 18

W1282X-326 3318

CFTR-

- ACCUUAUAGGUGGGCCUCU 19

W1282X-327 3319

CFTR-

- UACCU UAUAGGUGGGCCUCU 20

W1282X-47 3039

CFTR-

- UUACCUUAUAGGUGGGCCUCU 21

W1282X-328 3320

362

5535.1 CFTR-

- U UUACCUUAUAGGUGGGCCUCU 22

W1282X-329 3321

CFTR-

- UU UUACCUUAUAGGUGGGCCUCU 23

W1282X-330 3322

CFTR-

- CUU UUACCUUAUAGGUGGGCCUCU 24

W1282X-331 3323

CFTR-

- CUUAUAGGUGGGCCUCUU 18

W1282X-332 3324

CFTR-

- CCUUAUAGGUGGGCCUCUU 19

W1282X-333 3325

CFTR-

- ACCUUAUAGGUGGGCCUCUU 20

W1282X-60 3052

CFTR-

- UACCU UAUAGGUGGGCCUCUU 21

W1282X-334 3326

CFTR-

- UUACCUUAUAGGUGGGCCUCUU 22

W1282X-335 3327

CFTR-

- UU UACCUUAUAGGUGGGCCUCUU 23

W1282X-336 3328

CFTR-

- UU UUACCUUAUAGGUGGGCCUCUU 24

W1282X-337 3329

CFTR-

- ACUUUGUUAUCAGCUUUU 18

W1282X-338 3330

CFTR-

- UACUUUGUUAUCAGCUUUU 19

W1282X-339 3331

CFTR-

- GUACUUUGUUAUCAGCUUUU 20

W1282X-340 3332

CFTR-

- AGUACUUUGUUAUCAGCUUUU 21

W1282X-341 3333

CFTR-

- GAGUACUUUGUUAUCAGCUUUU 22

W1282X-342 3334

CFTR-

- AGAGUACUUUGUUAUCAGCUUUU 23

W1282X-343 3335

CFTR-

- AAGAGUACUUUGUUAUCAGCUUUU 24

W1282X-344 3336

Table 30A provides exemplary targeting domains for correcting a mutation (e.g., W1282X) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., W1282X), have a high level of orthogonality and start with a 5'G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting

363

5535.1 domains in the Table lean be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 30A

Table 30B provides exemplary targeting domains for correcting a mutation (e.g.,

W1282X) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., W1282X) and have a high level of orthogonality. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table lean be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 30B

Table 31A provides exemplary targeting domains for correcting a mutation (e.g., 3272- 26->G) in the CFTR gene selected according to the first tier parameters. The targeting domains

364

5535.1 bind within 200 bp from a mutation (e.g., 3272-26->G), have a high level of orthogonality and start with a 5'G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 31A

Table 31B provides exemplary targeting domains for correcting a mutation (e.g., 3272- 26->G) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., 3272-26->G) and have a high level of orthogonality. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 31B

365

5535.1 CFTR-3272-17 - CUAAUUUAGUCUU UUUC 17 1298

CFTR-3272-18 + CAUAUCACAAAUGUCAU 17 1299

CFTR-3272-19 + ACUUGGCUACCAGAGAU 17 1300

CFTR-3272-20 + UACCCUCUUU UUUUACU 17 1301

CFTR-3272-21 + CAGG U ACAAG AACCAG U 17 1302

CFTR-3272-22 - UGGACACUUCG UGCCU U 17 1303

CFTR-3272-23 - CAUCUUGUUACAAGCUUAAA 20 1304

CFTR-3272-24 - AAUCAUAUCUAUUCAAAGAA 20 1305

CFTR-3272-25 + UUUUACUUGGCUACCAGAGA 20 1306

CFTR-3272-26 + AAAGUAAGGCUGCCGUCCGA 20 1307

CFTR-3272-27 - UUACAAGCUUAAAAGGACUA 20 1308

CFTR-3272-28 + UGGAACAGAGUUU C A A AG U A 20 1309

CFTR-3272-29 - UGAAU UUACAUACUGCCAAC 20 1310

CFTR-3272-30 + U AAA AAG CUUUUUUUCACAC 20 1311

CFTR-3272-31 - UUUCUAUGGAAAUAUUUCAC 20 1312

CFTR-3272-32 - UGUACCUGUCAACACUGCGC 20 1313

CFTR-3272-33 - UAUGGAAAUAUUUCACAGGC 20 1314

CFTR-3272-34 - UGGUAGCCAAGU A A A A A A AG 20 1315

CFTR-3272-35 + UAUGUAAAUUCAGAGCUUUG 20 1316

CFTR-3272-36 + AAUCAUAUCACAAAUGUCAU 20 1317

CFTR-3272-37 + UUUACUUGGCUACCAGAGAU 20 1318

CFTR-3272-38 + AGUUACCCUCU UUUUU UACU 20 1319

CFTR-3272-39 + UGACAGGUACAAGAACCAGU 20 1320

CFTR-3272-40 - CUAUGGACACU UCGUGCCUU 20 1321

Table 31C provides exemplary targeting domains for correcting a mutation (e.g., 3272- 26->G) in the CFTR gene selected according to the third tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., 3272-26->G) and start with a 5'G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 31C

366

5535.1 Table 31D provides exemplary targeting domains for correcting a mutation (e.g., 3272- 26->G) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., 3272-26->G). It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 31D

Table 32A provides exemplary targeting domains for correcting a mutation (e.g., 3272- 26->G) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., 3272-26->G), have a high level of orthogonality, start with a 5'G, and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 32A

Table 32B provides exemplary targeting domains for correcting a mutation (e.g., 3272- 26->G) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., 3272-26->G), have a high level of

367

5535.1 orthogonality and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 32B

368

5535.1 CFTR-3272-83 - AACACUGCGCUGGUUCCAAAU 21 1364

CFTR-3272-84 - CAACACUGCGCUGGUUCCAAAU 22 1365

CFTR-3272-85 - UCAACACUGCGCUGGUUCCAAAU 23 1366

CFTR-3272-86 - ACUCUGUUCCACAAAGCU 18 1367

CFTR-3272-87 - AACUCUGUUCCACAAAGCU 19 1368

CFTR-3272-88 - AAACUCUGUUCCACAAAGCU 20 1369

Table 32C provides exemplary targeting domains for correcting a mutation (e.g., 3272- 26->G) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., 3272-26->G), and PAM is NNGRRT. It is

contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 32C

369

5535.1 CFTR-3272-108 - UCUCUGGUAGCCAAGU A A A A A A A 23 1390

CFTR-3272-109 - AUCUCUGGUAGCCAAGUAAAAAAA 24 1391

CFTR-3272-110 - CUAUGGAAAUAUUUCACAGGC 21 1392

CFTR-3272-111 - UCUAUGGAAAUAUUUCACAGGC 22 1393

CFTR-3272-112 - UUCUAUGGAAAUAUUUCACAGGC 23 1394

CFTR-3272-113 - UUUCUAUGGAAAUAUUUCACAGGC 24 1395

CFTR-3272-114 - GAAACUCUGUUCCACAAAGCU 21 1373

CFTR-3272-115 - UGAAACUCUGUUCCACAAAGCU 22 1396

CFTR-3272-116 - U UGAAACUC U G U U CC AC AAAG C U 23 1397

CFTR-3272-117 - UUUGAAACUCUGUUCCACAAAGCU 24 1398

Table 32D provides exemplary targeting domains for correcting a mutation (e.g., 3272- 26->G) in the CFTR gene selected according to the fifth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., 3272-26->G), and PAM is NNGRRV. It is

contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 32D

370

5535.1 CFTR-3272-

+ UGCCUGUGAAAUAUUUCCA 19

126 1407

CFTR-3272-

+ CUGCCUGUGAAAUAUUUCCA 20

127 1408

CFTR-3272-

+ CCUGCCUGUGAAAUAUUUCCA 21

128 1409

CFTR-3272-

+ UCCUGCCUGUGAAAUAUUUCCA 22

129 1410

CFTR-3272-

+ CUCCUGCCUGUGAAAUAUUUCCA 23

130 1411

CFTR-3272-

+ ACUCCUGCCUGUGAAAUAUUUCCA 24

131 1412

CFTR-3272-

+ UUACUUGGCUACCAGAGA 18

132 1413

CFTR-3272-

+ UUUACUUGGCUACCAGAGA 19

133 1414

CFTR-3272-

+ UUUUACUUGGCUACCAGAGA 20

25 1306

CFTR-3272-

+ UUUUUACUUGGCUACCAGAGA 21

134 1415

CFTR-3272-

+ UUUUUUACUUGGCUACCAGAGA 22

135 1416

CFTR-3272-

+ UUUUUUUACUUGGCUACCAGAGA 23

136 1417

CFTR-3272-

+ CUUUUUUUACUUGGCUACCAGAGA 24

137 1418

CFTR-3272-

+ AAGCUUGUAACAAGAUGA 18

138 1419

CFTR-3272-

+ UAAGCUUGUAACAAGAUGA 19

139 1420

CFTR-3272-

+ UUAAGCUUGUAACAAGAUGA 20

140 1421

CFTR-3272-

+ UUUAAGCUUGUAACAAGAUGA 21

141 1422

CFTR-3272-

+ UUUUAAGCUUGUAACAAGAUGA 22

142 1423

CFTR-3272-

+ CUU UUAAGCUUGUAACAAGAUGA 23

143 1424

CFTR-3272-

+ CCUUUUAAGCUUGUAACAAGAUGA 24

144 1425

CFTR-3272-

+ CUUUUUUUACUUGGCUAC 18

145 1426

CFTR-3272- + UCUUUUUUUACUUGGCUAC 19 1427

371

5535.1 146

CFTR-3272-

+ CUCUUUUUUUACUUGGCUAC 20

147 1428

CFTR-3272-

+ CCUCUUUUUUUACUUGGCUAC 21

148 1429

CFTR-3272-

+ CCCUCUUUUUUUACUUGGCUAC 22

149 1430

CFTR-3272-

+ ACCCUCUUUUUUUACUUGGCUAC 23

150 1431

CFTR-3272-

+ UACCCUCUUUUUUUACUUGGCUAC 24

151 1432

CFTR-3272-

+ CGCAGUGUUGACAGGUAC 18

152 1433

CFTR-3272-

+ GCGCAGUGUUGACAGGUAC 19

153 1434

CFTR-3272-

+ AGCGCAGUGUUGACAGGUAC 20

154 1435

CFTR-3272-

+ CAGCGCAGUGUUGACAGGUAC 21

155 1436

CFTR-3272-

+ CCAGCGCAGUGUUGACAGGUAC 22

156 1437

CFTR-3272-

+ ACCAGCGCAGUGUUGACAGGUAC 23

157 1438

CFTR-3272-

+ AACCAGCGCAGUGUUGACAGGUAC 24

158 1439

CFTR-3272-

+ UUUCAUAAUAUCUUGUAC 18

159 1440

CFTR-3272-

+ AUUUCAUAAUAUCUUGUAC 19

160 1441

CFTR-3272-

+ AAUUUCAUAAUAUCUUGUAC 20

161 1442

CFTR-3272-

+ UAAUUUCAUAAUAUCUUGUAC 21

162 1443

CFTR-3272-

+ GUAAUUUCAUAAUAUCUUGUAC 22

163 1444

CFTR-3272-

+ UGUAAUUUCAUAAUAUCUUGUAC 23

164 1445

CFTR-3272-

+ AUGUAAUUUCAUAAUAUCUUGUAC 24

165 1446

CFTR-3272-

+ AGGCUGCCGUCCGAAGGC 18

166 1447

CFTR-3272-

+ AAGGCUGCCGUCCGAAGGC 19

167 1448

372

5535.1 CFTR-3272-

+ UAAGGCUGCCGUCCGAAGGC 20

168 1449

CFTR-3272-

+ GUAAGGCUGCCGUCCGAAGGC 21

169 1450

CFTR-3272-

+ AGUAAGGCUGCCGUCCGAAGGC 22

170 1451

CFTR-3272-

+ AAGUAAGGCUGCCGUCCGAAGGC 23

171 1452

CFTR-3272-

+ AAAGUAAGGCUGCCGUCCGAAGGC 24

172 1453

CFTR-3272-

+ UUUACUUGGCUACCAGAG 18

173 1454

CFTR-3272-

+ UUUUACUUGGCUACCAGAG 19

174 1455

CFTR-3272-

+ UUUUUACUUGGCUACCAGAG 20

175 1456

CFTR-3272-

+ UUUUUUACUUGGCUACCAGAG 21

176 1457

CFTR-3272-

+ UUUUUUUACUUGGCUACCAGAG 22

177 1458

CFTR-3272-

+ CUUUUUUUACUUGGCUACCAGAG 23

178 1459

CFTR-3272-

+ UCUUUUUUUACUUGGCUACCAGAG 24

179 1460

CFTR-3272-

+ UGUAAAUUCAGAGCUUUG 18

180 1461

CFTR-3272-

+ AUGUAAAUUCAGAGCUUUG 19

181 1462

CFTR-3272-

+ UAUGUAAAUUCAGAGCUUUG 20

35 1316

CFTR-3272-

+ GUAUGUAAAUUCAGAGCUUUG 21

182 1463

CFTR-3272-

+ AGUAUGUAAAUUCAGAGCUUUG 22

183 1464

CFTR-3272-

+ CAGUAUGUAAAUUCAGAGCUUUG 23

184 1465

CFTR-3272-

+ GCAGUAUGUAAAUUCAGAGCUUUG 24

185 1466

CFTR-3272-

+ UACUUGGCUACCAGAGAU 18

186 1467

CFTR-3272-

+ UUACUUGGCUACCAGAGAU 19

187 1468

CFTR-3272- + UUUACUUGGCUACCAGAGAU 20 1318

373

5535.1 37

CFTR-3272-

+ UUUUACUUGGCUACCAGAGAU 21

188 1469

CFTR-3272-

+ UUUUUACUUGGCUACCAGAGAU 22

189 1470

CFTR-3272-

+ UUUUUUACUUGGCUACCAGAGAU 23

190 1471

CFTR-3272-

+ UUUUUUUACUUGGCUACCAGAGAU 24

191 1472

CFTR-3272-

+ AAAAUUGGACUCCUGCCU 18

192 1473

CFTR-3272-

+ GAAAAUUGGACUCCUGCCU 19

193 1474

CFTR-3272-

+ UGAAAAUUGGACUCCUGCCU 20

194 1475

CFTR-3272-

+ GUGAAAAUUGGACUCCUGCCU 21

195 1476

CFTR-3272-

+ AGUGAAAAUUGGACUCCUGCCU 22

196 1477

CFTR-3272-

+ GAGUGAAAAUUGGACUCCUGCCU 23

197 1478

CFTR-3272-

+ UGAGUGAAAAUUGGACUCCUGCCU 24

198 1479

CFTR-3272-

+ UCAAAGUAAGGCUGCCGU 18

199 1480

CFTR-3272-

+ UUCAAAGUAAGGCUGCCGU 19

200 1481

CFTR-3272-

+ UUUCAAAGUAAGGCUGCCGU 20

201 1482

CFTR-3272-

+ GUUUCAAAGUAAGGCUGCCGU 21

202 1483

CFTR-3272-

+ AGUUUCAAAGUAAGGCUGCCGU 22

203 1484

CFTR-3272-

+ GAGUUUCAAAGUAAGGCUGCCGU 23

204 1485

CFTR-3272-

+ AGAGUUUCAAAGUAAGGCUGCCGU 24

205 1486

CFTR-3272-

+ GUUGGCAGUAUGUAAAUU 18

206 1487

CFTR-3272-

+ AGUUGGCAGUAUGUAAAUU 19

207 1488

CFTR-3272-

+ CAGUUGGCAGUAUGUAAAUU 20

208 1489

374

5535.1 CFTR-3272-

+ CCAGU UGGCAGUAUGUAAAUU 21

209 1490

CFTR-3272-

+ ACCAGUUGGCAGUAUGUAAAUU 22

210 1491

CFTR-3272-

+ AACCAGUUGGCAGUAUGUAAAUU 23

211 1492

CFTR-3272-

+ G AACCAG U UGG CAG U AUG U AAAU U 24

212 1493

CFTR-3272-

+ AUGUAAAUUCAGAGCUUU 18

213 1494

CFTR-3272-

+ UAUGUAAAUUCAGAGCUUU 19

214 1495

CFTR-3272-

+ GUAUGUAAAUUCAGAGCUUU 20

215 1496

CFTR-3272-

+ AGUAUGUAAAUUCAGAGCUUU 21

216 1497

CFTR-3272-

+ CAGUAUGUAAAUUCAGAGCUUU 22

217 1498

CFTR-3272-

+ GCAGUAUGUAAAUUCAGAGCUUU 23

218 1499

CFTR-3272-

+ GGCAGUAUGUAAAUUCAGAGCUUU 24

219 1500

CFTR-3272-

- CUGGUAGC C A AG U A A A A A 18

220 1501

CFTR-3272-

- UCUGGUAGCCAAGU A A A A A 19

221 1502

CFTR-3272-

- CUCUGGUAGCCAAGU A A A A A 20

222 1503

CFTR-3272-

- UCUCUGGUAGCCAAGUAAAAA 21

223 1504

CFTR-3272-

- AUCUCUGGUAGCCAAGUAAAAA 22

224 1505

CFTR-3272-

- CAUCUCUGGUAGCCAAGU A A A A A 23

225 1506

CFTR-3272-

- CCAUCUCUGGUAGCCAAGUAAAAA 24

226 1507

CFTR-3272-

- ACACUGCGCUGGUUCCAA 18

227 1508

CFTR-3272-

- AACACUGCGCUGGUUCCAA 19

228 1509

CFTR-3272-

- CAACACUGCGCUGGUUCCAA 20

229 1510

CFTR-3272- - UCAACACUGCGCUGGU UCCAA 21 1511

375

5535.1 230

CFTR-3272-

- GUCAACACUGCGCUGGU UCCAA 22

231 1512

CFTR-3272-

- UGUCAACACUGCGCUGGUUCCAA 23

232 1513

CFTR-3272-

- CUGUCAACACUGCGCUGGUUCCAA 24

233 1514

CFTR-3272-

- GCUGGU UCCAAAUGAGAA 18

234 1515

CFTR-3272-

- CGCUGGU UCCAAAUGAGAA 19

235 1516

CFTR-3272-

- GCGCUGGU UCCAAAUGAGAA 20

236 1517

CFTR-3272-

- UGCGCUGGUUCCAAAUGAGAA 21

237 1518

CFTR-3272-

- CUGCGCUGGUUCCAAAUGAGAA 22

238 1519

CFTR-3272-

- ACUGCGCUGGUUCCAAAUGAGAA 23

239 1520

CFTR-3272-

- CACUGCGCUGGUUCCAAAUGAGAA 24

240 1521

CFTR-3272-

- AUCUUGUUACAAGCUUAA 18

241 1522

CFTR-3272-

- CAUCUUGUUACAAGCUUAA 19

242 1523

CFTR-3272-

- UCAUCUUGUUACAAGCUUAA 20

243 1524

CFTR-3272-

- CUCAUCUUGUUACAAGCUUAA 21

244 1525

CFTR-3272-

- ACUCAUCUUGUUACAAGCUUAA 22

245 1526

CFTR-3272-

- CACUCAUCUUGUUACAAGCUUAA 23

246 1527

CFTR-3272-

- UCACUCAUCUUGUUACAAGCUUAA 24

247 1528

CFTR-3272-

- UAUUUGCAGUGUUUUCUA 18

248 1529

CFTR-3272-

- UUAUUUGCAGUGUUUUCUA 19

249 1530

CFTR-3272-

- GUUAUUUGCAGUGUUUUCUA 20

42 1323

CFTR-3272-

- UGUUAUUUGCAGUGUUUUCUA 21

250 1531

376

5535.1 CFTR-3272-

- AUGUUAUUUGCAGUGU UUUCUA 22

251 1532

CFTR-3272-

- UAUGUUAUUUGCAGUGUUUUCUA 23

252 1533

CFTR-3272-

- UUAUGUUAUUUGCAGUGUUUUCUA 24

253 1534

CFTR-3272-

- AUGGAAAUAUUUCACAGG 18

254 1535

CFTR-3272-

- UAUGGAAAUAUUUCACAGG 19

255 1536

CFTR-3272-

- CUAUGGAAAUAUUUCACAGG 20

256 1537

CFTR-3272-

- UCUAUGGAAAUAUUUCACAGG 21

257 1538

CFTR-3272-

- UUCUAUGGAAAUAUUUCACAGG 22

258 1539

CFTR-3272-

- UU UCUAUGGAAAUAUU UCACAGG 23

259 1540

CFTR-3272-

- UU UUCUAUGGAAAUAU UUCACAGG 24

260 1541

CFTR-3272-

- UACAAGCUUAAAAGGACU 18

261 1542

CFTR-3272-

- UUACAAGCUUAAAAGGACU 19

262 1543

CFTR-3272-

- GU UACAAGCUUAAAAGGACU 20

263 1544

CFTR-3272-

- UGUUACAAGCUUAAAAGGACU 21

264 1545

CFTR-3272-

- U UG U UACAAGCU U AAAAGG ACU 22

265 1546

CFTR-3272-

- CUUGUUACAAGCUUAAAAGGACU 23

266 1547

CFTR-3272-

- UCUUGUUACAAGCUUAAAAGGACU 24

267 1548

CFTR-3272-

- UCGGACGGCAGCCU UACU 18

268 1549

CFTR-3272-

- UUCGGACGGCAGCCUUACU 19

269 1550

CFTR-3272-

- CUUCGGACGGCAGCCUUACU 20

270 1551

CFTR-3272-

- CCUUCGGACGGCAGCCU UACU 21

271 1552

CFTR-3272- - GCCUUCGGACGGCAGCCUUACU 22 1553

377

5535.1 272

CFTR-3272-

- UGCCUUCGGACGGCAGCCUUACU 23

273 1554

CFTR-3272-

- GUGCCU UCGGACGGCAGCCUUACU 24

274 1555

CFTR-3272-

- UAUGGACACUUCGUGCCU 18

275 1556

CFTR-3272-

- CUAUGGACACUUCGUGCCU 19

276 1557

CFTR-3272-

- ACUAUGGACACUUCGUGCCU 20

277 1558

CFTR-3272-

- GACUAUGGACACUUCGUGCCU 21

278 1559

CFTR-3272-

- GGACUAUGGACACUUCGUGCCU 22

279 1560

CFTR-3272-

- AGGACUAUGGACACUUCGUGCCU 23

280 1561

CFTR-3272-

- AAGGACUAUGGACACUUCGUGCCU 24

281 1562

CFTR-3272-

- UUAUUUGCAGUGU UUUCU 18

282 1563

CFTR-3272-

- GU UAUUUGCAGUGUUU UCU 19

283 1564

CFTR-3272-

- UGUUAUUUGCAGUGUU UUCU 20

284 1565

CFTR-3272-

- AUGUUAUUUGCAGUGUUUUCU 21

285 1566

CFTR-3272-

- UAUGUUAUUUGCAGUGUUUUCU 22

286 1567

CFTR-3272-

- UUAUGUUAUUUGCAGUGUUUUCU 23

287 1568

CFTR-3272-

- UU UAUGUUAUUUGCAGUGUUUUCU 24

288 1569

CFTR-3272-

- U C A A AG A A U G G C AC C AG U 18

289 1570

CFTR-3272-

- UUCAAAGAAUGGCACCAGU 19

290 1571

CFTR-3272-

- AUUCAAAGAAUGGCACCAGU 20

291 1572

CFTR-3272-

- UAUUCAAAGAAUGGCACCAGU 21

292 1573

CFTR-3272-

- CUAUUCAAAGAAUGGCACCAGU 22

293 1574

378

5535.1 CFTR-3272-

- UCUAUUCAAAGAAUGGCACCAGU 23

294 1575

CFTR-3272-

- AUCUAUUCAAAGAAUGGCACCAGU 24

295 1576

CFTR-3272-

- UUUCAGGUACAAGAUAUU 18

296 1577

CFTR-3272-

- UUUUCAGGUACAAGAUAUU 19

297 1578

CFTR-3272-

- UUUUUCAGGUACAAGAUAUU 20

298 1579

CFTR-3272-

- CUUUUUCAGGUACAAGAUAUU 21

299 1580

CFTR-3272-

- UCUUUUUCAGGUACAAGAUAUU 22

300 1581

CFTR-3272-

- GUCUUUUUCAGGUACAAGAUAUU 23

301 1582

CFTR-3272-

- AGUCUUUUUCAGGUACAAGAUAUU 24

302 1583

Table 33A provides exemplary targeting domains for correcting a mutation (e.g., 3272- 26->G) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., 3272-26->G) and have a high level of orthogonality. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break

(Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 33A

379

5535.1 Table 33B provides exemplary targeting domains for correcting a mutation (e.g., 3272- 26->G) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., 3272-26->G). It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 33B

Table 34A provides exemplary targeting domains for correcting a mutation (e.g.,

3849+10kbC->T) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within 500 bp from a mutation (e.g., 3849+10kbC->T), have a high level of orthogonality and start with a 5'G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 34A

380

5535.1 CFTR-3849-7 + GUUUUUAGGUUGGGAAAGAC 20 3350

CFTR-3849-8 + GCACAUAAUAAUUAGUUUCC 20 3351

CFTR-3849-9 + GAGAACUCAGUUUUUAGGUU 20 3352

CFTR-3849-10 - GAAAACACUGACUUAGAUUU 20 3353

Table 34B provides exemplary targeting domains for correcting a mutation (e.g., 3849+10kbC->T) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within 500 bp from a mutation (e.g., 3849+10kbC->T) and have a high level of orthogonality. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 34B

381

5535.1 CFTR-3849-34 - CAACAUUCUCAGGGAGG 17 3377

CFTR-3849-35 - AUCCAACAUUCUCAGGG 17 3378

CFTR-3849-36 + AUACAAUAUACCAUAUG 17 3379

CFTR-3849-37 - CAAUUAUAAUCACCUUG 17 3380

CFTR-3849-38 - UCUAUCUUGAUAAACAU 17 3381

CFTR-3849-39 - UAGUUGAAUCAUUCAGU 17 3382

CFTR-3849-40 + CUCCUCCCUGAGAAUGU 17 3383

CFTR-3849-41 - AAACAAG AAG ACU U UG U 17 3384

CFTR-3849-42 + AACUCAGUUUUUAGGUU 17 3385

CFTR-3849-43 - AAC AAG AAG AC U U U G U U 17 3386

CFTR-3849-44 - AACACUGACU UAGAUUU 17 3387

CFTR-3849-45 - UUUAAGGUCUAUACUU U 17 3388

CFTR-3849-46 - CAUCUGUUGCAGUAUUAAAA 20 3389

CFTR-3849-47 + U AU U U U CAAG AG ACU ACAAA 20 3390

CFTR-3849-48 + AUAUCUGACACAUUU UUCAA 20 3391

CFTR-3849-49 + AAUCU UUGGUUUAGCU UUAA 20 3392

CFTR-3849-50 - CUUGAUU UCUGGAGACCACA 20 3393

CFTR-3849-51 + UGACACAU UUUUCAAAGGCA 20 3394

CFTR-3849-52 - AUCUUGAUCCAACAUUCUCA 20 3395

CFTR-3849-53 + CAU U U U AAU ACUG CAACAG A 20 3396

CFTR-3849-54 + UCUCAGUGAUCUGUUGAAUA 20 3397

CFTR-3849-55 - CU U AAU CAAAAU U CCU CAU A 20 3398

CFTR-3849-56 - ACCAGCAGUUCAAUGAUAUA 20 3399

CFTR-3849-57 - AAAACACUGACUUAGAUUUA 20 3400

CFTR-3849-58 - AGAUAUUUGAUAGUACUUUA 20 3401

CFTR-3849-59 + UUUCAAAGGCAAGGAAUCAC 20 3402

CFTR-3849-60 - UAUUGUAUAUAUCACAGUAC 20 3403

CFTR-3849-61 - CAACAGAUCACUGAGAAGCC 20 3404

CFTR-3849-62 - AAGCCUGGAAAAACAAAUCC 20 3405

CFTR-3849-63 + UUUCCGGGAU UUGUUU UUCC 20 3406

CFTR-3849-64 + UCCUUAUAUCAUUGAACUGC 20 3407

CFTR-3849-65 - UGUCUUAAAAGCUUAU UUGC 20 3408

CFTR-3849-66 + AAAGGUUUUAGCUAUUACUC 20 3409

CFTR-3849-67 - UAUCUUGAUCCAACAUUCUC 20 3410

CFTR-3849-68 - UGACUUGUCAUCUUGAUUUC 20 3411

CFTR-3849-69 + UGAAUAGAACAUUUCCUUUC 20 3412

CFTR-3849-70 + UUGGGAAAGACUGGAUGAAG 20 3413

CFTR-3849-71 + UCAAAUAUCUAUUUAAUCAG 20 3414

CFTR-3849-72 - A A AG UAGUUGAAUCAUUCAG 20 3415

CFTR-3849-73 - AUCCAACAUUCUCAGGGAGG 20 3416

CFTR-3849-74 - UUGAUCCAACAUUCUCAGGG 20 3417

CFTR-3849-75 - AUUCAAUUAUAAUCACCUUG 20 3418

382

5535.1 CFTR-3849-76 - AUGUCU UAAAAGCUUAUUUG 20 3419

CFTR-3849-77 - UUUUCUAUCUUGAUAAACAU 20 3420

CFTR-3849-78 + AGAGAACUCAGUUUUUAGGU 20 3421

CFTR-3849-79 + CACCUCCUCCCUGAGAAUGU 20 3422

CFTR-3849-80 - UAUAAACAAGAAGACUUUGU 20 3423

CFTR-3849-81 + AAGUUAAACAGUGUUGAAUU 20 3424

CFTR-3849-82 - AUAAACAAGAAGACUUUGUU 20 3425

CFTR-3849-83 + AACAA AG C AAACAAG U AU U U 20 3426

CFTR-3849-84 - UACUUUAAGGUCUAUACUUU 20 3427

Table 34C provides exemplary targeting domains for correcting a mutation (e.g., 3849+10kbC->T) in the CFTR gene selected according to the third tier parameters. The targeting domains bind within 500 bp from a mutation (e.g., 3849+10kbC->T) and start with a 5'G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 34C

Table 34D provides exemplary targeting domains for correcting a mutation (e.g., 3849+10kbC->T) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within 500 bp from a mutation (e.g., 3849+10kbC->T). It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 34D

383

5535.1 4th Tier

Target Site

gRNA Name DNA Strand Targeting Domain

Length Seq ID

CFTR-3849-91 - UUUUUUUCUGAAGAAAA 17 3434

CFTR-3849-92 + U U U AU CAAG AU AG AAAA 17 3435

CFTR-3849-93 - CUGUUGCAGUAUUAAAA 17 3436

CFTR-3849-94 + U U U CAAG AG ACU ACAAA 17 3437

CFTR-3849-95 - AUUUUUUUCUGAAGAAA 17 3438

CFTR-3849-96 + CACAUUUUU C A A AG G C A 17 3439

CFTR-3849-97 - AAUUUAUAAGAAUAUCA 17 3440

CFTR-3849-98 + UAGAACAUUUCCUUUCA 17 3441

CFTR-3849-99 - AAUCAAAAUUCCUCAUA 17 3442

CFTR-3849-100 - UAUUUGAUAGUACUUUA 17 3443

CFTR-3849-101 - CCUGGAAAAACAAAUCC 17 3444

CFTR-3849-102 - CUUGUCAUCUUGAUUUC 17 3445

CFTR-3849-103 - UUUUUUCUGAAGAAAAG 17 3446

CFTR-3849-104 + UAUUUUUCAUUACCUUG 17 3447

CFTR-3849-105 - UCUUAAAAGCUUAUUUG 17 3448

CFTR-3849-106 + U U A U CAAG A U AG A A A A U 17 3449

CFTR-3849-107 + UUAAACAGUGUUGAAUU 17 3450

CFTR-3849-108 + A AAG C AAA CAAG U AU U U 17 3451

CFTR-3849-109 + UAGAGAACUCAGUUUUU 17 3452

CFTR-3849-110 + AUGUUUAUCAAGAUAGAAAA 20 3453

CFTR-3849-111 - AGUAUUUUUUUCUGAAGAAA 20 3454

CFTR-3849-112 + AACUG AAAU U U AG AU CCACA 20 3455

CFTR-3849-113 - AAUAAUUUAUAAGAAUAUCA 20 3456

CFTR-3849-114 + AGUCUUCUUGUUUAUAUAAC 20 3457

CFTR-3849-115 - UAUUUUUUUCUGAAGAAAAG 20 3458

CFTR-3849-116 + UAUAUACAAUAUACCAUAUG 20 3459

CFTR-3849-117 + AAUUAUUUUUCAUUACCUUG 20 3460

CFTR-3849-118 + UGUUUAUCAAGAUAGAAAAU 20 3461

CFTR-3849-119 - AAGUAGUUGAAUCAUUCAGU 20 3462

CFTR-3849-120 + AGAGGCAAUUUGUAAAUCUU 20 3463

CFTR-3849-121 + UUUUAGAGAACUCAGUUUUU 20 3464

Table 35A provides exemplary targeting domains for correcting a mutation (e.g., 3849+10kbC->T) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within 500 bp from a mutation (e.g., 3849+10kbC->T), have a high level of orthogonality, start with a 5'G, and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base

384

5535.1 pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 35A

385

5535.1 139

CFTR-3849-

- GCAGUUCAAUGAUAUAAGGAAAC 23

140 3483

CFTR-3849-

- GUAAUGAAAAAUAAUUAC 18

141 3484

CFTR-3849-

- GG U AAUG AAAAAU AAU U AC 19

142 3485

CFTR-3849-

- GAAAUAAUUUAUAAGAAUAUC 21

143 3486

CFTR-3849-

- GAUAAACAUUGGUGUAAAGUAG 22

144 3487

CFTR-3849-

- GUUAUAUAAACAAGAAGACUUUG 23

145 3488

CFTR-3849-

- GAAAACACUGACUUAGAUU 19

146 3489

CFTR-3849-

- GUACUUUAAGGUCUAUACUU 20

147 3490

CFTR-3849-

- GAUAGUACUUUAAGGUCUAUACUU 24

148 3491

CFTR-3849-

- GAUUCAAUUAUAAUCACCUU 20

149 3492

Table 35B provides exemplary targeting domains for correcting a mutation (e.g., 3849+10kbC->T) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within 500 bp from a mutation (e.g., 3849+10kbC->T), have a high level of orthogonality and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 35B

386

5535.1 CFTR-3849-

+ AUCCACAAGGUGAUUAUAA 19

152 3495

CFTR-3849-

+ AUAUGCUGCUUAUACCCA 18

153 3496

CFTR-3849-

+ AAUAUGCUGCUUAUACCCA 19

154 3497

CFTR-3849-

+ ACACAUUUUUCAAAGGCA 18

155 3498

CFTR-3849-

+ UGACACAUUUUUCAAAGGCA 20

51 3394

CFTR-3849-

+ CUGACACAUUUUUCAAAGGCA 21

156 3499

CFTR-3849-

+ UCUGACACAUUUUUCAAAGGCA 22

157 3500

CFTR-3849-

+ AUCUGACACAUUU UUCAAAGGCA 23

158 3501

CFTR-3849-

+ UAUCUGACACAUU UUUCAAAGGCA 24

159 3502

CFTR-3849-

+ UUUUUAGGUUGGGAAAGA 18

160 3503

CFTR-3849-

+ AGUUUUUAGGUUGGGAAAGA 20

161 3504

CFTR-3849-

+ CAGUUUUUAGGUUGGGAAAGA 21

162 3505

CFTR-3849-

+ UCAGUUUUUAGGU UGGGAAAGA 22

163 3506

CFTR-3849-

+ CUCAGUUUUUAGGUUGGGAAAGA 23

164 3507

CFTR-3849-

+ ACUCAGUUUUUAGGUUGGGAAAGA 24

165 3508

CFTR-3849-

+ CUGUAAUUGCAUUGUACC 18

166 3509

CFTR-3849-

+ AGCUGUAAUUGCAUUGUACC 20

167 3510

CFTR-3849-

+ UAGCUGUAAUUGCAUUGUACC 21

168 3511

CFTR-3849-

+ CUAGCUGUAAUUGCAU UGUACC 22

169 3512

CFTR-3849-

+ UGCUAGCUGUAAUUGCAUUGUACC 24

170 3513

CFTR-3849-

+ UGAUCUGUUGAAUAAGGC 18

171 3514

CFTR-3849- + AGUGAUCUGUUGAAUAAGGC 20 3515

387

5535.1 172

CFTR-3849-

+ CAGUGAUCUGUUGAAUAAGGC 21

173 3516

CFTR-3849-

+ UCAGUGAUCUGU UGAAUAAGGC 22

174 3517

CFTR-3849-

+ CUCAGUGAUCUGUUGAAUAAGGC 23

175 3518

CFTR-3849-

+ UCUCAGUGAUCUGUUGAAUAAGGC 24

176 3519

CFTR-3849-

+ CACAU AAU AAU U AG U U U C 18

177 3520

CFTR-3849-

+ UGGCACAUAAUAAUUAGUUUC 21

178 3521

CFTR-3849-

+ CUGGCACAUAAUAAUUAGUUUC 22

179 3522

CFTR-3849-

+ ACUGGCACAUAAUAAUUAGUUUC 23

180 3523

CFTR-3849-

+ AACUGGCACAUAAUAAUUAGUUUC 24

181 3524

CFTR-3849-

+ ACCUCCUCCCUGAGAAUG 18

182 3525

CFTR-3849-

+ CACCUCCUCCCUGAGAAUG 19

183 3526

CFTR-3849-

+ UGCACCUCCUCCCUGAGAAUG 21

184 3527

CFTR-3849-

+ AUGCACCUCCUCCCUGAGAAUG 22

185 3528

CFTR-3849-

+ AAUGCACCUCCUCCCUGAGAAUG 23

186 3529

CFTR-3849-

+ CAAUGCACCUCCUCCCUGAGAAUG 24

187 3530

CFTR-3849-

+ AAGUCCAGAUUUAUCAUG 18

188 3531

CFTR-3849-

+ UAAGUCCAGAUUUAUCAUG 19

189 3532

CFTR-3849-

+ U UAAG U CCAG AU U U AU CAUG 20

190 3533

CFTR-3849-

+ AUUAAGUCCAGAUUUAUCAUG 21

191 3534

CFTR-3849-

+ UGAUUAAGUCCAGAUU UAUCAUG 23

192 3535

CFTR-3849-

+ U UGAUUAAGUCCAGAU UUAUCAUG 24

193 3536

388

5535.1 CFTR-3849-

+ UAUACAAUAUACCAUAUG 18

194 3537

CFTR-3849-

+ AUAUACAAUAUACCAUAUG 19

195 3538

CFTR-3849-

+ UAUAUACAAUAUACCAUAUG 20

116 3459

CFTR-3849-

+ AUAUAUACAAUAUACCAUAUG 21

196 3539

CFTR-3849-

+ UGAUAUAUACAAUAUACCAUAUG 23

197 3540

CFTR-3849-

+ AGGCUUCUCAGUGAUCUG 18

198 3541

CFTR-3849-

+ CAGGCUUCUCAGUGAUCUG 19

199 3542

CFTR-3849-

+ CCAGGCUUCUCAGUGAUCUG 20

200 3543

CFTR-3849-

+ UCCAGGCU UCUCAGUGAUCUG 21

201 3544

CFTR-3849-

+ U UCCAGGCUUCUCAGUGAUCUG 22

202 3545

CFTR-3849-

+ U UUCCAGGCUUCUCAGUGAUCUG 23

203 3546

CFTR-3849-

+ U UUUCCAGGCUUCUCAGUGAUCUG 24

204 3547

CFTR-3849-

+ UGUUGAAAGUUAAACAGUG 19

205 3548

CFTR-3849-

+ AUGUUGAAAGUUAAACAGUG 20

206 3549

CFTR-3849-

+ UAUGUUGAAAGUUAAACAGUG 21

207 3550

CFTR-3849-

+ AUAUGUUGAAAGUUAAACAGUG 22

208 3551

CFTR-3849-

+ AAUAUGUUGAAAGUUAAACAGUG 23

209 3552

CFTR-3849-

+ UAAUAUGUUGAAAGUUAAACAGUG 24

210 3553

CFTR-3849-

+ UGUUUGUGCUGAUAUGAU 18

211 3554

CFTR-3849-

+ AGGUGUUUGUGCUGAUAUGAU 21

212 3555

CFTR-3849-

+ UAGGUGUUUGUGCUGAUAUGAU 22

213 3556

CFTR-3849- + UUAGGUGUUUGUGCUGAUAUGAU 23 3557

389

5535.1 214

CFTR-3849-

+ UUUAGGUGUUUGUGCUGAUAUGAU 24

215 3558

CFTR-3849-

+ UCAAUGCACCUCCUCCCU 18

216 3559

CFTR-3849-

+ UUCAAUGCACCUCCUCCCU 19

217 3560

CFTR-3849-

+ CUUCAAUGCACCUCCUCCCU 20

218 3561

CFTR-3849-

+ ACU UCAAUGCACCUCCUCCCU 21

219 3562

CFTR-3849-

+ AACUUCAAUGCACCUCCUCCCU 22

220 3563

CFTR-3849-

+ UAACUUCAAUGCACCUCCUCCCU 23

221 3564

CFTR-3849-

+ AUAACUUCAAUGCACCUCCUCCCU 24

222 3565

CFTR-3849-

+ U UAAUGAAACAUAGUAUU 18

223 3566

CFTR-3849-

+ AUUAAUGAAACAUAGUAUU 19

224 3567

CFTR-3849-

+ UAUUAAUGAAACAUAGUAUU 20

225 3568

CFTR-3849-

+ UUAUUAAUGAAACAUAGUAUU 21

226 3569

CFTR-3849-

+ AUUAUUAAUGAAACAUAGUAUU 22

227 3570

CFTR-3849-

+ AAUUAUUAAUGAAACAUAGUAUU 23

228 3571

CFTR-3849-

+ UAAUUAUUAAUGAAACAUAGUAUU 24

229 3572

CFTR-3849-

+ CAUGAAUAGAACAUUUCCUUU 21

230 3573

CFTR-3849-

+ CCAU G AAU AG AACAU U U CCU U U 22

231 3574

CFTR-3849-

+ ACCAUGAAUAGAACAUUUCCUUU 23

232 3575

CFTR-3849-

+ UACCAUGAAUAGAACAUUUCCUUU 24

233 3576

CFTR-3849-

- UCUUUCCCAACCUAAAAA 18

234 3577

CFTR-3849-

- AGUCUUUCCCAACCUAAAAA 20

235 3578

390

5535.1 CFTR-3849-

- CAGUCUUUCCCAACCUAAAAA 21

236 3579

CFTR-3849-

- CCAGUCUU UCCCAACCUAAAAA 22

237 3580

CFTR-3849-

- UCCAGUCU UUCCCAACCUAAAAA 23

238 3581

CFTR-3849-

- AUCCAGUCUU UCCCAACCUAAAAA 24

239 3582

CFTR-3849-

- AAGUAGUUGAAUCAUUCA 18

240 3583

CFTR-3849-

- AAAGUAGUUGAAUCAUUCA 19

241 3584

CFTR-3849-

- UAAAGUAGUUGAAUCAUUCA 20

242 3585

CFTR-3849-

- AUUGUAUAUAUCACAGUA 18

243 3586

CFTR-3849-

- UAUUGUAUAUAUCACAGUA 19

244 3587

CFTR-3849-

- AUAUUGUAUAUAUCACAGUA 20

245 3588

CFTR-3849-

- UCAAUGAUAUAAGGAAAC 18

246 3589

CFTR-3849-

- UUCAAUGAUAUAAGGAAAC 19

247 3590

CFTR-3849-

- AGUUCAAUGAUAUAAGGAAAC 21

248 3591

CFTR-3849-

- CAGUUCAAUGAUAUAAGGAAAC 22

249 3592

CFTR-3849-

- AGCAGUUCAAUGAUAUAAGGAAAC 24

250 3593

CFTR-3849-

- AGGUAAUGAAAAAUAAUUAC 20

251 3594

CFTR-3849-

- AGAAAUAAUUUAUAAGAAUAUC 22

252 3595

CFTR-3849-

- CAG AAAU AAU U U AU AAG AAU AU C 23

253 3596

CFTR-3849-

- UCAGAAAUAAUUUAUAAGAAUAUC 24

254 3597

CFTR-3849-

- AACAUUGGUGUAAAGUAG 18

255 3598

CFTR-3849-

- AAACAUUGGUGUAAAGUAG 19

256 3599

CFTR-3849- - UAAACAUUGGUGUAAAGUAG 20 3600

391

5535.1 257

CFTR-3849-

- AUAAACAUUGGUGUAAAGUAG 21

258 3601

CFTR-3849-

- UGAUAAACAUUGGUGUAAAGUAG 23

259 3602

CFTR-3849-

- U U GAU AAACAU UGG UG U AAAG U AG 24

260 3603

CFTR-3849-

- UGUUGCAGUAUUAAAAUG 18

261 3604

CFTR-3849-

- CUGU UGCAGUAU UAAAAUG 19

262 3605

CFTR-3849-

- UCUGUUGCAGUAUUAAAAUG 20

263 3606

CFTR-3849-

- AUCUGUUGCAGUAUUAAAAUG 21

264 3607

CFTR-3849-

- CAUCUGUUGCAGUAUUAAAAUG 22

265 3608

CFTR-3849-

- CCAUCUGU UGCAGUAU UAAAAUG 23

266 3609

CFTR-3849-

- UCCAUCUGUUGCAGUAUUAAAAUG 24

267 3610

CFTR-3849-

- AU AAACAAG AAG ACU U UG 18

268 3611

CFTR-3849-

- UAU AAACAAG AAG ACU U UG 19

269 3612

CFTR-3849-

- AUAUAAACAAGAAGACUUUG 20

270 3613

CFTR-3849-

- U AU AU AAACAAG AAG ACU U UG 21

271 3614

CFTR-3849-

- U U AU AU AAACAAG AAG ACU U UG 22

272 3615

CFTR-3849-

- AG U U AU AU AAACAAG AAG ACU U UG 24

273 3616

CFTR-3849-

- AAAACACUGACUUAGAU U 18

274 3617

CFTR-3849-

- AG AAAACACUG ACU U AG AU U 20

275 3618

CFTR-3849-

- UAGAAAACACUGACUUAGAUU 21

276 3619

CFTR-3849-

- UUAGAAAACACUGACUUAGAUU 22

277 3620

CFTR-3849-

- AUUAGAAAACACUGACUUAGAUU 23

278 3621

392

5535.1 CFTR-3849-

- UAUUAGAAAACACUGACUUAGAUU 24

279 3622

CFTR-3849-

- ACU UUAAGGUCUAUACUU 18

280 3623

CFTR-3849-

- UACUUUAAGGUCUAUACUU 19

281 3624

CFTR-3849-

- AGUACUUUAAGGUCUAUACUU 21

282 3625

CFTR-3849-

- UAGUACUUUAAGGUCUAUACUU 22

283 3626

CFTR-3849-

- AUAGUACUUUAAGGUCUAUACUU 23

284 3627

CFTR-3849-

- U U CAAU UAUAAUCACCU U 18

285 3628

CFTR-3849-

- AUUCAAUUAUAAUCACCUU 19

286 3629

CFTR-3849-

- AGAUUCAAUUAUAAUCACCUU 21

287 3630

CFTR-3849-

- AAGAUUCAAUUAUAAUCACCUU 22

288 3631

CFTR-3849-

- A A AG A U U CAAU UAUAAUCACCUU 23

289 3632

CFTR-3849-

- AAAAGAU U CAAU UAUAAUCACCUU 24

290 3633

Table 35C provides exemplary targeting domains for correcting a mutation (e.g., 3849+10kbC->T) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within 500 bp from a mutation (e.g., 3849+10kbC->T), and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 35C

393

5535.1 292

CFTR-3849-

+ CCAAUG U U UAU CAAG AU AG AAAA 23

293 3636

CFTR-3849-

+ ACCAAUG U U UAU CAAG AU AG AAAA 24

294 3637

CFTR-3849-

+ AGAUCCACAAGGUGAUUAUAA 21

295 3638

CFTR-3849-

+ UAGAUCCACAAGGUGAUUAUAA 22

296 3639

CFTR-3849-

+ UUAGAUCCACAAGGUGAUUAUAA 23

297 3640

CFTR-3849-

+ UUUAGAUCCACAAGGUGAUUAUAA 24

298 3641

CFTR-3849-

+ AGAAUAUGCUGCUUAUACCCA 21

299 3642

CFTR-3849-

+ GAGAAUAUGCUGCUUAUACCCA 22

300 3643

CFTR-3849-

+ UGAGAAUAUGCUGCUUAUACCCA 23

301 3644

CFTR-3849-

+ UUGAGAAUAUGCUGCU UAUACCCA 24

302 3645

CFTR-3849-

+ G AAU AG AACAU U U CCU U U 18

303 3646

CFTR-3849-

+ UGAAUAGAACAUUUCCUUU 19

304 3647

CFTR-3849-

+ AUGAAUAGAACAUUUCCUUU 20

305 3648

CFTR-3849-

- GUAAAGUAGUUGAAUCAUUCA 21

306 3649

CFTR-3849-

- UGUAAAGUAGUUGAAUCAUUCA 22

307 3650

CFTR-3849-

- GUGUAAAGUAGUUGAAUCAUUCA 23

308 3651

CFTR-3849-

- GGUGUAAAGUAGUUGAAUCAUUCA 24

309 3652

CFTR-3849-

- UAUAUUGUAUAUAUCACAGUA 21

310 3653

CFTR-3849-

- GUAUAUUGUAUAUAUCACAGUA 22

311 3654

CFTR-3849-

- GGUAUAUUGUAUAUAUCACAGUA 23

312 3655

CFTR-3849-

- UGGUAUAUUGUAUAUAUCACAGUA 24

313 3656

394

5535.1 CFTR-3849-

- AAGGUAAUGAAAAAUAAUUAC 21

314 3657

CFTR-3849-

- C A AG G U A A U G A A A A A U A A U U AC 22

315 3658

CFTR-3849-

- ACAAGG U AAUG AAAAAU AAU U AC 23

316 3659

CFTR-3849-

- CACAAGGUAAUGAAAAAUAAUUAC 24

317 3660

CFTR-3849-

- AUAAUUUAUAAGAAUAUC 18

318 3661

CFTR-3849-

- AAUAAUUUAUAAGAAUAUC 19

319 3662

CFTR-3849-

- AAAUAAUUUAUAAGAAUAUC 20

320 3663

CFTR-3849-

- AU U U CAG AAAU AAU U U AU 18

321 3664

CFTR-3849-

- AAU U U CAG AAAU AAU U U AU 19

322 3665

CFTR-3849-

- AAAU U U CAG AAAU AAU U U AU 20

323 3666

CFTR-3849-

- G AAAU U U CAG AAAU AAU U U AU 21

324 3667

CFTR-3849-

- AG AAAU U U CAG AAAU AAU U U AU 22

325 3668

CFTR-3849-

- CAG AAAU U U CAG AAAU AAU U U AU 23

326 3669

CFTR-3849-

- A CAG AAAU U U CAG AAAU AAU U U AU 24

327 3670

Table 35D provides exemplary targeting domains for correcting a mutation (e.g., 3849+10kbC->T) in the CFTR gene selected according to the fifth tier parameters. The targeting domains bind within 500 bp from a mutation (e.g., 3849+10kbC->T), and PAM is NNGRRV. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 35D

395

5535.1 Length

CFTR-3849-

+ U U U U CAAG AG ACU ACAAA 18

328 3671

CFTR-3849-

+ AU U U U CAAG AG ACU ACAAA 19

329 3672

CFTR-3849-47 + U AU U U U CAAG AG ACU ACAAA 20 3390

CFTR-3849-

+ G U AU U U U CAAG AG ACU ACAAA 21

330 3673

CFTR-3849-

+ UGUAUUUUCAAGAGACUACAAA 22

331 3674

CFTR-3849-

+ CUGUAUUUU CAAG AG ACU ACAAA 23

332 3675

CFTR-3849-

+ UCUGUAUUUUCAAGAGACUACAAA 24

333 3676

CFTR-3849-

+ UGUUUAUCAAGAUAGAAA 18

334 3677

CFTR-3849-

+ AUG U U U AU CAAG AU AG AAA 19

335 3678

CFTR-3849-

+ AAUGUUUAUCAAGAUAGAAA 20

336 3679

CFTR-3849-

+ CAAUGUUUAUCAAGAUAGAAA 21

337 3680

CFTR-3849-

+ CCAAUG U U U AU CAAG AU AG AAA 22

338 3681

CFTR-3849-

+ ACCAAUGUUUAUCAAGAUAGAAA 23

339 3682

CFTR-3849-

+ CACCAAUG U U U AU CAAG AU AG AAA 24

340 3683

CFTR-3849-

+ AUUUUCAAGAGACUACAA 18

341 3684

CFTR-3849-

+ UAUUUUCAAGAGACUACAA 19

342 3685

CFTR-3849-

+ GU AUUUUCAAGAGACUACAA 20

343 3686

CFTR-3849-

+ UGUAUUUUCAAGAGACUACAA 21

344 3687

CFTR-3849-

+ CUGUAUUUUCAAGAGACUACAA 22

345 3688

CFTR-3849-

+ UCUGUAUUUU CAAG AG ACU ACAA 23

346 3689

CFTR-3849-

+ U UCUGUAUUUU CAAG AG ACU ACAA 24

347 3690

CFTR-3849- + AUCAAGAUGACAAGUCAA 18 3691

396

5535.1 348

CFTR-3849-

+ AAUCAAGAUGACAAGUCAA 19

349 3692

CFTR-3849-

+ AAAUCAAGAUGACAAGUCAA 20

350 3693

CFTR-3849-

+ GAAAUCAAGAUGACAAGUCAA 21

351 3694

CFTR-3849-

+ AGAAAUCAAGAUGACAAGUCAA 22

352 3695

CFTR-3849-

+ C AG AAA U C A AG A U G AC A AG U C A A 23

353 3696

CFTR-3849-

+ CCAGAAAUCAAGAUGACAAGUCAA 24

354 3697

CFTR-3849-

+ AUUGCAUUGUACCAUGAA 18

355 3698

CFTR-3849-

+ AAUUGCAUUGUACCAUGAA 19

356 3699

CFTR-3849-

+ UAAUUGCAUUGUACCAUGAA 20

357 3700

CFTR-3849-

+ GUAAUUGCAUUGUACCAUGAA 21

358 3701

CFTR-3849-

+ UGUAAUUGCAUUGUACCAUGAA 22

359 3702

CFTR-3849-

+ CUGUAAUUGCAUUGUACCAUGAA 23

360 3703

CFTR-3849-

+ GCUGUAAUUGCAU UGUACCAUGAA 24

361 3704

CFTR-3849-

+ CAAAUAUCUAUUUAAUCA 18

362 3705

CFTR-3849-

+ UCAAAUAUCUAUUUAAUCA 19

363 3706

CFTR-3849-

+ AUCAAAUAUCUAUUUAAUCA 20

364 3707

CFTR-3849-

+ UAUCAAAUAUCUAUUUAAUCA 21

365 3708

CFTR-3849-

+ CUAUCAAAUAUCUAUUUAAUCA 22

366 3709

CFTR-3849-

+ ACUAUCAAAUAUCUAUUUAAUCA 23

367 3710

CFTR-3849-

+ UACUAUCAAAUAUCUAUUUAAUCA 24

368 3711

CFTR-3849-

+ UCUGGUUUCCUUAUAUCA 18

369 3712

397

5535.1 CFTR-3849-

+ CUCUGGUU UCCUUAUAUCA 19

370 3713

CFTR-3849-

+ ACUCUGGUUUCCU UAUAUCA 20

371 3714

CFTR-3849-

+ UACUCUGGUUUCCUUAUAUCA 21

372 3715

CFTR-3849-

+ U UACUCUGGUUUCCUUAUAUCA 22

373 3716

CFTR-3849-

+ AUUACUCUGGU UUCCU UAUAUCA 23

374 3717

CFTR-3849-

+ UAUUACUCUGGUUUCCUUAUAUCA 24

375 3718

CFTR-3849-

+ CACCAAUG U U U AU CAAG A 18

376 3719

CFTR-3849-

+ ACACCAAUG U U U AU CAAG A 19

377 3720

CFTR-3849-

+ U ACACCAAUG U U U AU CAAG A 20

378 3721

CFTR-3849-

+ UUACACCAAUGUU UAUCAAGA 21

379 3722

CFTR-3849-

+ UUUACACCAAUGU UUAUCAAGA 22

380 3723

CFTR-3849-

+ CUU UACACCAAUGUUUAUCAAGA 23

381 3724

CFTR-3849-

+ ACU U U ACACCAAUG U U U AU CAAG A 24

382 3725

CFTR-3849-

+ UUUUAAUACUGCAACAGA 18

383 3726

CFTR-3849-

+ AUUUUAAUACUGCAACAGA 19

384 3727

CFTR-3849-53 + CAU U U U AAU ACUG CAACAG A 20 3396

CFTR-3849-

+ CCAUUUUAAUACUGCAACAGA 21

385 3728

CFTR-3849-

+ ACCAUUUUAAUACUGCAACAGA 22

386 3729

CFTR-3849-

+ CACCAU UUUAAUACUGCAACAGA 23

387 3730

CFTR-3849-

+ UCACCAUUUUAAUACUGCAACAGA 24

388 3731

CFTR-3849-

+ UAUUAAUGAAACAUAGUA 18

389 3732

CFTR-3849-

+ UUAUUAAUGAAACAUAGUA 19

390 3733

398

5535.1 CFTR-3849-

+ AUUAUUAAUGAAACAUAGUA 20

391 3734

CFTR-3849-

+ AAU U AU U AAUG AAACAU AG U A 21

392 3735

CFTR-3849-

+ UAAUUAUUAAUGAAACAUAGUA 22

393 3736

CFTR-3849-

+ UUAAUUAUUAAUGAAACAUAGUA 23

394 3737

CFTR-3849-

+ AUUAAUUAUUAAUGAAACAUAGUA 24

395 3738

CFTR-3849-

+ UAUCUCUAUUAAUUAUUA 18

396 3739

CFTR-3849-

+ AUAUCUCUAUUAAUUAUUA 19

397 3740

CFTR-3849-

+ UAUAUCUCUAUUAAUUAUUA 20

398 3741

CFTR-3849-

+ AUAUAUCUCUAUUAAUUAUUA 21

399 3742

CFTR-3849-

+ CAUAUAUCUCUAUUAAUUAUUA 22

400 3743

CFTR-3849-

+ UCAUAUAUCUCUAUUAAUUAUUA 23

401 3744

CFTR-3849-

+ UUCAUAUAUCUCUAUUAAUUAUUA 24

402 3745

CFTR-3849-

+ AAAAU ACU AAAAU U U U U A 18

403 3746

CFTR-3849-

+ AAAAAU ACU AAAAU U U U U A 19

404 3747

CFTR-3849-

+ AAAAAAU ACU AAAAU U U U U A 20

405 3748

CFTR-3849-

+ AAAAAAAU ACU AAAAU U U U U A 21

406 3749

CFTR-3849-

+ G AAAAAAAU ACU AAAAU U U U U A 22

407 3750

CFTR-3849-

+ AG AAAAAAAU ACU AAAAU U U U U A 23

408 3751

CFTR-3849-

+ CAG AAAAAAAU ACU AAAAU U U U U A 24

409 3752

CFTR-3849-

+ CUUCAAUGCACCUCCUCC 18

410 3753

CFTR-3849-

+ ACU UCAAUGCACCUCCUCC 19

411 3754

CFTR-3849- + AACUUCAAUGCACCUCCUCC 20 3755

399

5535.1 412

CFTR-3849-

+ UAACUUCAAUGCACCUCCUCC 21

413 3756

CFTR-3849-

+ AUAACUUCAAUGCACCUCCUCC 22

414 3757

CFTR-3849-

+ AAUAACUUCAAUGCACCUCCUCC 23

415 3758

CFTR-3849-

+ UAAUAACUUCAAUGCACCUCCUCC 24

416 3759

CFTR-3849-

+ GACACAUUUUUCAAAGGC 18

417 3760

CFTR-3849-

+ UGACACAUUUUU CAAAG G C 19

418 3761

CFTR-3849-

+ CUGACACAUUUU UCAAAGGC 20

419 3762

CFTR-3849-

+ UCUGACACAUUU UUCAAAGGC 21

420 3763

CFTR-3849-

+ AUCUGACACAUUUUUCAAAGGC 22

421 3764

CFTR-3849-

+ UAUCUGACACAUUUUUCAAAGGC 23

422 3765

CFTR-3849-

+ AUAUCUGACACAUUU UUCAAAGGC 24

423 3766

CFTR-3849-

+ AUUAAGUCCAGAUUUAUC 18

424 3767

CFTR-3849-

+ GAUUAAGUCCAGAUUUAUC 19

425 3768

CFTR-3849-

+ UGAUUAAGUCCAGAUU UAUC 20

426 3769

CFTR-3849-

+ U UGAUUAAGUCCAGAU UUAUC 21

427 3770

CFTR-3849-

+ U UUGAUUAAGUCCAGAUUUAUC 22

428 3771

CFTR-3849-

+ U UUUGAUUAAGUCCAGAUUUAUC 23

429 3772

CFTR-3849-

+ AUUUUGAUUAAGUCCAGAUUUAUC 24

430 3773

CFTR-3849-

+ UCAUUACCUUGUGGUCUC 18

431 3774

CFTR-3849-

+ UUCAUUACCUUGUGGUCUC 19

432 3775

CFTR-3849-

+ UUUCAUUACCUUGUGGUCUC 20

433 3776

400

5535.1 CFTR-3849-

+ UUUUCAUUACCUUGUGGUCUC 21

434 3777

CFTR-3849-

+ UUUUUCAUUACCUUGUGGUCUC 22

435 3778

CFTR-3849-

+ AUUUUUCAUUACCUUGUGGUCUC 23

436 3779

CFTR-3849-

+ UAUUUUUCAUUACCUUGUGGUCUC 24

437 3780

CFTR-3849-

+ UGAAAUUUCUGUAUUUUC 18

438 3781

CFTR-3849-

+ CUGAAAUUUCUGUAU UUUC 19

439 3782

CFTR-3849-

+ UCUGAAAUUUCUGUAUUUUC 20

440 3783

CFTR-3849-

+ UUCUGAAAUUUCUGUAUUUUC 21

441 3784

CFTR-3849-

+ UUUCUGAAAUUUCUGUAUUUUC 22

442 3785

CFTR-3849-

+ AUUUCUGAAAUUUCUGUAUUUUC 23

443 3786

CFTR-3849-

+ UAUUUCUGAAAUUUCUGUAUUUUC 24

444 3787

CFTR-3849-

+ AUUUUAAUACUGCAACAG 18

445 3788

CFTR-3849-

+ CAUUUUAAUACUGCAACAG 19

446 3789

CFTR-3849-

+ CCAU U U U AAU ACU GCAACAG 20

447 3790

CFTR-3849-

+ ACCAUUUUAAUACUGCAACAG 21

448 3791

CFTR-3849-

+ CACCAUUUUAAUACUGCAACAG 22

449 3792

CFTR-3849-

+ U CACCAU U U U AAU ACUG CAACAG 23

450 3793

CFTR-3849-

+ CUCACCAU UUUAAUACUGCAACAG 24

451 3794

CFTR-3849-

+ GAGAACUCAGUUUUUAGG 18

452 3795

CFTR-3849-

+ AGAGAACUCAGUUUUUAGG 19

453 3796

CFTR-3849-

+ UAGAGAACUCAGUUUU UAGG 20

454 3797

CFTR-3849- + UUAGAGAACUCAGUUU UUAGG 21 3798

401

5535.1 455

CFTR-3849-

+ U UUAGAGAACUCAGUU UUUAGG 22

456 3799

CFTR-3849-

+ U U U U AG AG AACU CAG U U U U U AGG 23

457 3800

CFTR-3849-

+ U U U U U AG AG AACU CAG U U U U U AGG 24

458 3801

CFTR-3849-

+ UAGGUUGGGAAAGACUGG 18

459 3802

CFTR-3849-

+ UUAGGUUGGGAAAGACUGG 19

460 3803

CFTR-3849-

+ UUUAGGUUGGGAAAGACUGG 20

461 3804

CFTR-3849-

+ UUUUAGGUUGGGAAAGACUGG 21

462 3805

CFTR-3849-

+ UUUUUAGGUUGGGAAAGACUGG 22

463 3806

CFTR-3849-

+ GUUUUUAGGUUGGGAAAGACUGG 23

464 3807

CFTR-3849-

+ AGUUUUUAGGUUGGGAAAGACUGG 24

465 3808

CFTR-3849-

+ UUCAAGAGACUACAAAUG 18

466 3809

CFTR-3849-

+ U U U CAAG AG ACU ACAAAUG 19

467 3810

CFTR-3849-

+ U U U U CAAG AG ACU ACAAAUG 20

468 3811

CFTR-3849-

+ AUUUUCAAGAGACUACAAAUG 21

469 3812

CFTR-3849-

+ UAUUUUCAAGAGACUACAAAUG 22

470 3813

CFTR-3849-

+ G U AU U U U CAAG AG ACU ACAAAUG 23

471 3814

CFTR-3849-

+ UGUAUUUUCAAGAGACUACAAAUG 24

472 3815

CFTR-3849-

+ GU UGGGAAAGACUGGAUG 18

473 3816

CFTR-3849-

+ GGU UGGGAAAGACUGGAUG 19

474 3817

CFTR-3849-

+ AGGUUGGGAAAGACUGGAUG 20

475 3818

CFTR-3849-

+ UAGGUUGGGAAAGACUGGAUG 21

476 3819

402

5535.1 CFTR-3849-

+ UUAGGUUGGGAAAGACUGGAUG 22

477 3820

CFTR-3849-

+ U UUAGGUUGGGAAAGACUGGAUG 23

478 3821

CFTR-3849-

+ U UUUAGGUUGGGAAAGACUGGAUG 24

479 3822

CFTR-3849-

+ AUAAAUCAAAAUAAUAUG 18

480 3823

CFTR-3849-

+ GAUAAAUCAAAAUAAUAUG 19

481 3824

CFTR-3849-

+ AGAUAAAUCAAAAUAAUAUG 20

482 3825

CFTR-3849-

+ AAGAUAAAUCAAAAUAAUAUG 21

483 3826

CFTR-3849-

+ CAAGAUAAAUCAAAAUAAUAUG 22

484 3827

CFTR-3849-

+ UCAAGAUAAAUCAAAAUAAUAUG 23

485 3828

CFTR-3849-

+ AUCAAGAUAAAUCAAAAUAAUAUG 24

486 3829

CFTR-3849-

+ AUCAAAUAUCUAUUUAAU 18

487 3830

CFTR-3849-

+ UAUCAAAUAUCUAUUUAAU 19

488 3831

CFTR-3849-

+ CUAUCAAAUAUCUAUUUAAU 20

489 3832

CFTR-3849-

+ ACUAUCAAAUAUCUAUU UAAU 21

490 3833

CFTR-3849-

+ UACUAUCAAAUAUCUAU UUAAU 22

491 3834

CFTR-3849-

+ GUACUAUCAAAUAUCUAUUUAAU 23

492 3835

CFTR-3849-

+ AGUACUAUCAAAUAUCUAUUUAAU 24

493 3836

CFTR-3849-

+ AUAUAUACAAUAUACCAU 18

494 3837

CFTR-3849-

+ GAUAUAUACAAUAUACCAU 19

495 3838

CFTR-3849-

+ UGAUAUAUACAAUAUACCAU 20

496 3839

CFTR-3849-

+ GUGAUAUAUACAAUAUACCAU 21

497 3840

CFTR-3849- + UGUGAUAUAUACAAUAUACCAU 22 3841

403

5535.1 498

CFTR-3849-

+ CUGUGAUAUAUACAAUAUACCAU 23

499 3842

CFTR-3849-

+ ACUGUGAUAUAUACAAUAUACCAU 24

500 3843

CFTR-3849-

+ AUAUACAAUAUACCAUAU 18

501 3844

CFTR-3849-

+ UAUAUACAAUAUACCAUAU 19

502 3845

CFTR-3849-

+ AUAUAUACAAUAUACCAUAU 20

503 3846

CFTR-3849-

+ GAUAUAUACAAUAUACCAUAU 21

504 3847

CFTR-3849-

+ UGAUAUAUACAAUAUACCAUAU 22

505 3848

CFTR-3849-

+ GUGAUAUAUACAAUAUACCAUAU 23

506 3849

CFTR-3849-

+ UGUGAUAUAUACAAUAUACCAUAU 24

507 3850

CFTR-3849-

+ AGAACUCAGUUUUUAGGU 18

508 3851

CFTR-3849-

+ GAGAACUCAGUUUUUAGGU 19

509 3852

CFTR-3849-78 + AGAGAACUCAGUUUUUAGGU 20 3421

CFTR-3849-

+ UAGAGAACUCAGUUUU UAGGU 21

510 3853

CFTR-3849-

+ U UAGAGAACUCAGUUU UUAGGU 22

511 3854

CFTR-3849-

+ U U U AG AG AACU CAG UU UUUAGGU 23

512 3855

CFTR-3849-

+ U U U U AG AG AACU CAG U UUUUAGGU 24

513 3856

CFTR-3849-

+ GAACUCAGUUUUUAGGUU 18

514 3857

CFTR-3849-

+ AGAACUCAGUUUUUAGGUU 19

515 3858

CFTR-3849-9 + GAG AACU CAG U U U U U AGG U U 20 3352

CFTR-3849-

+ AGAGAACUCAGUUUUUAGGUU 21

516 3859

CFTR-3849-

+ UAGAGAACUCAGUUUU UAGGUU 22

517 3860

CFTR-3849-

+ U U AG AG AACU CAG UUU UUAGGUU 23

518 3861

404

5535.1 CFTR-3849-

+ U U U AG AG AACU CAG UU UUUAGGUU 24

519 3862

CFTR-3849-

+ UAUUCUUAUAAAUUAU UU 18

520 3863

CFTR-3849-

+ AUAUUCUUAUAAAUUAUUU 19

521 3864

CFTR-3849-

+ GAUAUUCUUAUAAAUUAUUU 20

522 3865

CFTR-3849-

+ UGAUAUUCUUAUAAAU UAUUU 21

523 3866

CFTR-3849-

+ UUGAUAUUCUUAUAAAUUAUUU 22

524 3867

CFTR-3849-

+ CUUGAUAUUCUUAUAAAUUAUUU 23

525 3868

CFTR-3849-

+ CCUUGAUAUUCUUAUAAAUUAUUU 24

526 3869

CFTR-3849-

+ G CACAU AAU AAU U AG U U U 18

527 3870

CFTR-3849-

+ GGCACAUAAUAAUUAGU UU 19

528 3871

CFTR-3849-

+ UGGCACAUAAUAAUUAGUUU 20

529 3872

CFTR-3849-

+ CUGGCACAUAAUAAUUAGUUU 21

530 3873

CFTR-3849-

+ ACUGGCACAUAAUAAUUAGUUU 22

531 3874

CFTR-3849-

+ AACUGGCACAUAAUAAUUAGUUU 23

532 3875

CFTR-3849-

+ UAACUGGCACAUAAUAAUUAGUUU 24

533 3876

CFTR-3849-

+ AAAAAAU ACU AAAAU U U U 18

534 3877

CFTR-3849-

+ AAAAAAAU ACU AAAAU U U U 19

535 3878

CFTR-3849-

+ G AAAAAAAU ACU AAAAU U U U 20

536 3879

CFTR-3849-

+ AG AAAAAAAU ACU AAAAU U U U 21

537 3880

CFTR-3849-

+ CAG AAAAAAAU ACU AAAAU U U U 22

538 3881

CFTR-3849-

+ U CAG AAAAAAAU ACU AAAAU U U U 23

539 3882

CFTR-3849- + U U CAG AAAAAAAU ACU AAAAU U U U 24 3883

405

5535.1 540

CFTR-3849-

- AUUUUUUUCUGAAGAAAA 18

541 3884

CFTR-3849-

- UAUUUUUUUCUGAAGAAAA 19

542 3885

CFTR-3849-87 - GUAUUUUUUUCUGAAGAAAA 20 3430

CFTR-3849-

- AGUAUUUUUUUCUGAAGAAAA 21

543 3886

CFTR-3849-

- UAGUAUUUUUUU CUGAAGAAAA 22

544 3887

CFTR-3849-

- UUAGUAUUUUUUUCUGAAGAAAA 23

545 3888

CFTR-3849-

- UU UAGUAUUUUUU UCUGAAGAAAA 24

546 3889

CFTR-3849-

- UAUUUUUUUCUGAAGAAA 18

547 3890

CFTR-3849-

- GUAUUUUUUUCUGAAGAAA 19

548 3891

CFTR-3849-

- AGUAUUUUUUUCUGAAGAAA 20

111 3454

CFTR-3849-

- UAGUAUUUUUUUCUGAAGAAA 21

549 3892

CFTR-3849-

- UUAGUAUUUUUUUCUGAAGAAA 22

550 3893

CFTR-3849-

- UU UAGUAUUUUUU UCUGAAGAAA 23

551 3849

CFTR-3849-

- UU UUAGUAUUUUU UUCUGAAGAAA 24

552 3895

CFTR-3849-

- GUAUUUUUUUCUGAAGAA 18

553 3896

CFTR-3849-

- AGUAUUUUUUUCUGAAGAA 19

554 3897

CFTR-3849-

- UAGUAUUUUUUUCUGAAGAA 20

555 3898

CFTR-3849-

- UUAGUAUUUUUUUCUGAAGAA 21

556 3899

CFTR-3849-

- UUUAGUAUUUUUUUCUGAAGAA 22

557 3900

CFTR-3849-

- UUUUAGUAUUUUUUUCUGAAGAA 23

558 3901

CFTR-3849-

- AUUUUAGUAUUUUU UUCUGAAGAA 24

559 3902

CFTR-3849- - UGAGUAAGACACCCUGAA 18 3903

406

5535.1 560

CFTR-3849-

- GUGAGUAAGACACCCUGAA 19

561 3904

CFTR-3849-88 - GGUGAGUAAGACACCCUGAA 20 3431

CFTR-3849-

- UGGUGAGUAAGACACCCUGAA 21

562 3905

CFTR-3849-

- AUGGUGAGUAAGACACCCUGAA 22

563 3906

CFTR-3849-

- AAUGGUGAGUAAGACACCCUGAA 23

564 3907

CFTR-3849-

- AAAUGGUGAGUAAGACACCCUGAA 24

565 3908

CFTR-3849-

- UGUUUCAUUAAUAAUUAA 18

566 3909

CFTR-3849-

- AUGUUUCAUUAAUAAU UAA 19

567 3910

CFTR-3849-

- UAUGUUUCAUUAAUAAUUAA 20

568 3911

CFTR-3849-

- CUAUGUUUCAU UAAUAAUUAA 21

569 3912

CFTR-3849-

- ACUAUGUUUCAUUAAUAAUUAA 22

570 3913

CFTR-3849-

- UACUAUGUUUCAUUAAUAAUUAA 23

571 3914

CFTR-3849-

- AUACUAUGUUUCAU UAAUAAUUAA 24

572 3915

CFTR-3849-

- UCUCAGGGAGGAGGUGCA 18

573 3916

CFTR-3849-

- UUCUCAGGGAGGAGGUGCA 19

574 3917

CFTR-3849-

- AUUCUCAGGGAGGAGGUGCA 20

575 3918

CFTR-3849-

- CAU UCUCAGGGAGGAGGUGCA 21

576 3919

CFTR-3849-

- ACAUUCUCAGGGAGGAGGUGCA 22

577 3920

CFTR-3849-

- AACAUUCUCAGGGAGGAGGUGCA 23

578 3921

CFTR-3849-

- CAACAUUCUCAGGGAGGAGGUGCA 24

579 3922

CFTR-3849-

- GCCUUAUUCAACAGAUCA 18

580 3923

CFTR-3849- - AGCCUUAUUCAACAGAUCA 19 3924

407

5535.1 581

CFTR-3849-

- UAGCCUUAUUCAACAGAUCA 20

582 3925

CFTR-3849-

- CUAGCCUUAU UCAACAGAUCA 21

583 3926

CFTR-3849-

- UCUAGCCU UAUUCAACAGAUCA 22

584 3927

CFTR-3849-

- CUCUAGCCUUAUUCAACAGAUCA 23

585 3928

CFTR-3849-

- ACUCUAGCCUUAUUCAACAGAUCA 24

586 3929

CFTR-3849-

- CUUGAUCCAACAUUCUCA 18

587 3930

CFTR-3849-

- UCU UGAUCCAACAUUCUCA 19

588 3931

CFTR-3849-52 - AUCUUGAUCCAACAUUCUCA 20 3395

CFTR-3849-

- UAUCUUGAUCCAACAUUCUCA 21

589 3932

CFTR-3849-

- UUAUCUUGAUCCAACAU UCUCA 22

590 3933

CFTR-3849-

- UUUAUCUUGAUCCAACAUUCUCA 23

591 3934

CFTR-3849-

- AUUUAUCUUGAUCCAACAUUCUCA 24

592 3935

CFTR-3849-

- GUGAGUAAGACACCCUGA 18

593 3936

CFTR-3849-

- GGUGAGUAAGACACCCUGA 19

594 3937

CFTR-3849-

- UGGUGAGUAAGACACCCUGA 20

595 3938

CFTR-3849-

- AUGGUGAGUAAGACACCCUGA 21

596 3939

CFTR-3849-

- AAUGGUGAGUAAGACACCCUGA 22

597 3940

CFTR-3849-

- AAAUGGUGAGUAAGACACCCUGA 23

598 3941

CFTR-3849-

- AAAAUGGUGAGUAAGACACCCUGA 24

599 3942

CFTR-3849-

- UGUAGUCUCUUGAAAAUA 18

600 3943

CFTR-3849-

- UUGUAGUCUCUUGAAAAUA 19

601 3944

CFTR-3849- - UUUGUAGUCUCUUGAAAAUA 20 3945

408

5535.1 602

CFTR-3849-

- AUUUGUAGUCUCUUGAAAAUA 21

603 3946

CFTR-3849-

- CAUUUGUAGUCUCUUGAAAAUA 22

604 3947

CFTR-3849-

- CCAUU UGUAGUCUCU UGAAAAUA 23

605 3948

CFTR-3849-

- UCCAU UUGUAGUCUCUUGAAAAUA 24

606 3949

CFTR-3849-

- CAGCAGUUCAAUGAUAUA 18

607 3950

CFTR-3849-

- CCAGCAGU UCAAUGAUAUA 19

608 3951

CFTR-3849-56 - ACCAGCAGUUCAAUGAUAUA 20 3399

CFTR-3849-

- UACCAGCAGUUCAAUGAUAUA 21

609 3952

CFTR-3849-

- UUACCAGCAGUUCAAUGAUAUA 22

610 3953

CFTR-3849-

- AUUACCAGCAGUUCAAUGAUAUA 23

611 3954

CFTR-3849-

- CAUUACCAGCAGUUCAAUGAUAUA 24

612 3955

CFTR-3849-

- UCUGGAGACCACAAGGUA 18

613 3956

CFTR-3849-

- UUCUGGAGACCACAAGGUA 19

614 3957

CFTR-3849-

- UUUCUGGAGACCACAAGGUA 20

615 3958

CFTR-3849-

- AUUUCUGGAGACCACAAGGUA 21

616 3959

CFTR-3849-

- GAUUUCUGGAGACCACAAGGUA 22

617 3960

CFTR-3849-

- UGAUUUCUGGAGACCACAAGGUA 23

618 3961

CFTR-3849-

- UUGAUUUCUGGAGACCACAAGGUA 24

619 3962

CFTR-3849-

- UGUGCCAGUUAUAUAAAC 18

620 3963

CFTR-3849-

- AUGUGCCAGUUAUAUAAAC 19

621 3964

CFTR-3849-

- UAUGUGCCAGUUAUAUAAAC 20

622 3965

CFTR-3849- - UUAUGUGCCAGUUAUAUAAAC 21 3966

409

5535.1 623

CFTR-3849-

- AUUAUGUGCCAGU UAUAUAAAC 22

624 3967

CFTR-3849-

- UAUUAUGUGCCAGUUAUAUAAAC 23

625 3968

CFTR-3849-

- UUAUUAUGUGCCAGUUAUAUAAAC 24

626 3969

CFTR-3849-

- AAUGGUGAGUAAGACACC 18

627 3970

CFTR-3849-

- AAAUGGUGAGUAAGACACC 19

628 3971

CFTR-3849-

- AAAAUGGUGAGUAAGACACC 20

629 3972

CFTR-3849-

- UAAAAUGGUGAGUAAGACACC 21

630 3973

CFTR-3849-

- UUAAAAUGGUGAGUAAGACACC 22

631 3974

CFTR-3849-

- AU UAAAAUGGUGAGUAAGACACC 23

632 3975

CFTR-3849-

- UAUUAAAAUGGUGAGUAAGACACC 24

633 3976

CFTR-3849-

- ACAGAUCACUGAGAAGCC 18

634 3977

CFTR-3849-

- AACAGAUCACUGAGAAGCC 19

635 3978

CFTR-3849-61 - CAACAGAUCACUGAGAAGCC 20 3404

CFTR-3849-

- UCAACAGAUCACUGAGAAGCC 21

636 3979

CFTR-3849-

- UUCAACAGAUCACUGAGAAGCC 22

637 3980

CFTR-3849-

- AUUCAACAGAUCACUGAGAAGCC 23

638 3981

CFTR-3849-

- UAUUCAACAGAUCACUGAGAAGCC 24

639 3982

CFTR-3849-

- GCCUGGAAAAACAAAUCC 18

640 3983

CFTR-3849-

- AGCCUGGAAAAACAAAUCC 19

641 3984

CFTR-3849-62 - AAGCCUGGAAAAACAAAUCC 20 3405

CFTR-3849-

- GAAGCCUGGAAAAACAAAUCC 21

642 3985

CFTR-3849-

- AGAAGCCUGGAAAAACAAAUCC 22

643 3986

410

5535.1 CFTR-3849-

- GAGAAGCCU G G A A A A AC A A A U C C 23

644 3987

CFTR-3849-

- UGAGAAGCCUGGAAAAACAAAUCC 24

645 3988

CFTR-3849-

- AACAGAUCACUGAGAAGC 18

646 3989

CFTR-3849-

- CAACAGAUCACUGAGAAGC 19

647 3990

CFTR-3849-

- UCAACAGAUCACUGAGAAGC 20

648 3991

CFTR-3849-

- UUCAACAGAUCACUGAGAAGC 21

649 3992

CFTR-3849-

- AUUCAACAGAUCACUGAGAAGC 22

650 3993

CFTR-3849-

- UAUUCAACAGAUCACUGAGAAGC 23

651 3994

CFTR-3849-

- UUAUUCAACAGAUCACUGAGAAGC 24

652 3995

CFTR-3849-

- UCU UAAAAGCUUAUUUGC 18

653 3996

CFTR-3849-

- GUCUUAAAAGCUUAUU UGC 19

654 3997

CFTR-3849-65 - UGUCUUAAAAGCUUAU UUGC 20 3408

CFTR-3849-

- AUGUCUUAAAAGCUUAUUUGC 21

655 3998

CFTR-3849-

- UAUGUCUUAAAAGCUUAUUUGC 22

656 3999

CFTR-3849-

- GUAUGUCUUAAAAGCUUAUUUGC 23

657 4000

CFTR-3849-

- GGUAUGUCUUAAAAGCUUAUUUGC 24

658 4001

CFTR-3849-

- AG CC U G G AAAAAC AAAU C 18

659 4002

CFTR-3849-

- AAGCCUGGAAAAACAAAUC 19

660 4003

CFTR-3849-

- GAAGCCUGGAAAAACAAAUC 20

661 4004

CFTR-3849-

- AGAAGCCUGGAAAAACAAAUC 21

662 4005

CFTR-3849-

- GAGAAGCCU G G A A A A AC A A A U C 22

663 4006

CFTR-3849-

- UGAGAAGCCUGGAAAAACAAAUC 23

664 4007

411

5535.1 CFTR-3849-

- CUGAGAAGCCUGGAAAAACAAAUC 24

665 4008

CFTR-3849-

- UUCUCCAU UUGUAGUCUC 18

666 4009

CFTR-3849-

- UU UCUCCAUUUGUAGUCUC 19

667 4010

CFTR-3849-

- CUU UCUCCAUUUGUAGUCUC 20

668 4011

CFTR-3849-

- GCUU UCUCCAUUUGUAGUCUC 21

669 4012

CFTR-3849-

- UGCU UUCUCCAUUUGUAGUCUC 22

670 4013

CFTR-3849-

- CUGCUU UCUCCAUUUGUAGUCUC 23

671 4014

CFTR-3849-

- ACUGCUUUCUCCAU UUGUAGUCUC 24

672 4015

CFTR-3849-

- UCUUGAUCCAACAUUCUC 18

673 4016

CFTR-3849-

- AUCUUGAUCCAACAUUCUC 19

674 4017

CFTR-3849-67 - UAUCUUGAUCCAACAUUCUC 20 3410

CFTR-3849-

- UUAUCUUGAUCCAACAUUCUC 21

675 4018

CFTR-3849-

- UU UAUCUUGAUCCAACAUUCUC 22

676 4019

CFTR-3849-

- AUUUAUCUUGAUCCAACAUUCUC 23

677 4020

CFTR-3849-

- GAUUUAUCUUGAUCCAACAUUCUC 24

678 4021

CFTR-3849-

- ACUUGUCAUCUUGAUUUC 18

679 4022

CFTR-3849-

- GACU UGUCAUCUUGAU UUC 19

680 4023

CFTR-3849-68 - UGACUUGUCAUCUUGAUUUC 20 3411

CFTR-3849-

- UUGACUUGUCAUCUUGAUUUC 21

681 4024

CFTR-3849-

- GU UGACUUGUCAUCUUGAUUUC 22

682 4025

CFTR-3849-

- AGUUGACUUGUCAUCU UGAUUUC 23

683 4026

CFTR-3849-

- CAGUUGACUUGUCAUCUUGAUUUC 24

684 4027

CFTR-3849- - UUUU UUUCUGAAGAAAAG 18 4028

412

5535.1 685

CFTR-3849-

- AUUUUUUUCUGAAGAAAAG 19

686 4029

CFTR-3849-

- UAUUUUUUU CUG AAG AAAAG 20

115 3458

CFTR-3849-

- GU AUUUUUUUCUGAAGAAAAG 21

687 4030

CFTR-3849-

- AGUAUUUUUUUCUGAAGAAAAG 22

688 4031

CFTR-3849-

- UAGUAUUUUUUU CUG AAG AAAAG 23

689 4032

CFTR-3849-

- UU AG UAUUUUUUU CUG AAG AAAAG 24

690 4033

CFTR-3849-

- UGAUCCAACAUUCUCAGG 18

691 4034

CFTR-3849-

- UUGAUCCAACAUUCUCAGG 19

692 4035

CFTR-3849-

- CUUGAUCCAACAUUCUCAGG 20

693 4036

CFTR-3849-

- UCUUGAUCCAACAUUCUCAGG 21

694 4037

CFTR-3849-

- AUCUUGAUCCAACAUUCUCAGG 22

695 4038

CFTR-3849-

- UAUCUUGAUCCAACAUUCUCAGG 23

696 4039

CFTR-3849-

- UUAUCUUGAUCCAACAUUCUCAGG 24

697 4040

CFTR-3849-

- GAUCCAACAUUCUCAGGG 18

698 4041

CFTR-3849-

- UGAUCCAACAUUCUCAGGG 19

699 4042

CFTR-3849-74 - UUGAUCCAACAUUCUCAGGG 20 3417

CFTR-3849-

- CUUGAUCCAACAUUCUCAGGG 21

700 4043

CFTR-3849-

- UCUUGAUCCAACAUUCUCAGGG 22

701 4044

CFTR-3849-

- AUCUUGAUCCAACAUUCUCAGGG 23

702 4045

CFTR-3849-

- UAUCUUGAUCCAACAUUCUCAGGG 24

703 4046

CFTR-3849-

- UAAGGUCUAUACUUU UGG 18

704 4047

CFTR-3849- - UUAAGGUCUAUACUU UUGG 19 4048

413

5535.1 705

CFTR-3849-

- UUUAAGGUCUAUACUUUUGG 20

706 4049

CFTR-3849-

- CUUUAAGGUCUAUACUUUUGG 21

707 4050

CFTR-3849-

- ACUUUAAGGUCUAUACUUUUGG 22

708 4051

CFTR-3849-

- UACUUUAAGGUCUAUACUUUUGG 23

709 4052

CFTR-3849-

- GUACUUUAAGGUCUAUACUUUUGG 24

710 4053

CFTR-3849-

- UUUUAGUAUUUUUUUCUG 18

711 4054

CFTR-3849-

- AUUUUAGUAUUUUUUUCUG 19

712 4055

CFTR-3849-

- AAUUUUAGUAUUUUUUUCUG 20

713 4056

CFTR-3849-

- AAAUUUUAGUAUUUUUUUCUG 21

714 4057

CFTR-3849-

- AAAAUUUUAGUAUUUUUUUCUG 22

715 4058

CFTR-3849-

- AAAAAUUUUAGUAUUUUUUUCUG 23

716 4059

CFTR-3849-

- UAAAAAUUUUAGUAUUUUUUUCUG 24

717 4060

CFTR-3849-

- GUCUUAAAAGCUUAUUUG 18

718 4061

CFTR-3849-

- UGUCUUAAAAGCUUAUUUG 19

719 4062

CFTR-3849-76 - AUGUCUUAAAAGCUUAUUUG 20 3419

CFTR-3849-

- UAUGUCUUAAAAGCUUAUUUG 21

720 4063

CFTR-3849-

- GUAUGUCUUAAAAGCUUAUUUG 22

721 4064

CFTR-3849-

- GGUAUGUCUUAAAAGCUUAUUUG 23

722 4065

CFTR-3849-

- GGGUAUGUCUUAAAAGCUUAUUUG 24

723 4066

CFTR-3849-

- AAUAAUUAAUAGAGAUAU 18

724 4067

CFTR-3849-

- UAAUAAUUAAUAGAGAUAU 19

725 4068

CFTR-3849- - UUAAUAAUUAAUAGAGAUAU 20 4069

414

5535.1 726

CFTR-3849-

- AUUAAUAAUUAAUAGAGAUAU 21

727 4070

CFTR-3849-

- CAU UAAUAAUUAAUAGAGAUAU 22

728 4071

CFTR-3849-

- UCAUUAAUAAUUAAUAGAGAUAU 23

729 4072

CFTR-3849-

- UUCAUUAAUAAUUAAUAGAGAUAU 24

730 4073

CFTR-3849-

- CCAG CAG U U CAAUG AU AU 18

731 4074

CFTR-3849-

- ACCAGCAGUUCAAUGAUAU 19

732 4075

CFTR-3849-

- UACCAGCAGUUCAAUGAUAU 20

733 4076

CFTR-3849-

- UUACCAGCAGUUCAAUGAUAU 21

734 4077

CFTR-3849-

- AUUACCAGCAGUUCAAUGAUAU 22

735 4078

CFTR-3849-

- CAU UACCAGCAGU UCAAUGAUAU 23

736 4079

CFTR-3849-

- GCAU UACCAGCAGUUCAAUGAUAU 24

737 4080

CFTR-3849-

- GAGGUGCAUUGAAGUUAU 18

738 4081

CFTR-3849-

- GGAGGUGCAUUGAAGU UAU 19

739 4082

CFTR-3849-

- AGGAGGUGCAUUGAAGUUAU 20

740 4083

CFTR-3849-

- GAGGAGGUGCAUUGAAGUUAU 21

741 4084

CFTR-3849-

- GGAGGAGGUGCAUUGAAGUUAU 22

742 4085

CFTR-3849-

- GGGAGGAGGUGCAUUGAAGUUAU 23

743 4086

CFTR-3849-

- AGGGAGGAGGUGCAUUGAAGUUAU 24

744 4087

CFTR-3849-

- CUUAUUCAACAGAUCACU 18

745 4088

CFTR-3849-

- CCUUAUUCAACAGAUCACU 19

746 4089

CFTR-3849-

- GCCUUAUUCAACAGAUCACU 20

747 4090

415

5535.1 CFTR-3849-

- AGCCU UAUUCAACAGAUCACU 21

748 4091

CFTR-3849-

- UAGCCU UAUUCAACAGAUCACU 22

749 4092

CFTR-3849-

- CUAGCCU UAUUCAACAGAUCACU 23

750 4093

CFTR-3849-

- UCUAGCCUUAUUCAACAGAUCACU 24

751 4094

CFTR-3849-

- ACCAGUGAUUCCUUGCCU 18

752 4095

CFTR-3849-

- AACCAGUGAUUCCUUGCCU 19

753 4096

CFTR-3849-

- AAACCAGUGAUUCCU UGCCU 20

754 4097

CFTR-3849-

- CAAACCAGUGAUUCCUUGCCU 21

755 4098

CFTR-3849-

- ACAAACCAGUGAUUCCUUGCCU 22

756 4099

CFTR-3849-

- UACAAACCAGUGAUUCCUUGCCU 23

757 4100

CFTR-3849-

- GUACAAACCAGUGAUUCCUUGCCU 24

758 4101

CFTR-3849-

- AUCUUGAUCCAACAUUCU 18

759 4102

CFTR-3849-

- UAUCUUGAUCCAACAUUCU 19

760 4103

CFTR-3849-

- UUAUCUUGAUCCAACAU UCU 20

761 4104

CFTR-3849-

- UUUAUCUUGAUCCAACAUUCU 21

762 4105

CFTR-3849-

- AUUUAUCUUGAUCCAACAUUCU 22

763 4106

CFTR-3849-

- GAUUUAUCUUGAUCCAACAUUCU 23

764 4107

CFTR-3849-

- UGAUUUAUCUUGAUCCAACAUUCU 24

765 4108

CFTR-3849-

- U UG AAAAU ACAG AAAU U U 18

766 4109

CFTR-3849-

- CUUGAAAAUACAGAAAUUU 19

767 4110

CFTR-3849-

- UCUUGAAAAUACAGAAAUUU 20

768 4111

CFTR-3849- - CUCUUGAAAAUACAGAAAUUU 21 4112

416

5535.1 769

CFTR-3849-

- U CU CU UG AAAAU ACAG AAAU U U 22

770 4113

CFTR-3849-

- G U CU CU UG AAAAU ACAG AAAU U U 23

771 4114

CFTR-3849-

- AG U CU CU UG AAAAU ACAG AAAU U U 24

772 4115

CFTR-3849-

- GACUUGUCAUCUUGAUUU 18

773 4116

CFTR-3849-

- UGACUUGUCAUCUUGAUUU 19

774 4117

CFTR-3849-

- UUGACUUGUCAUCUUGAUUU 20

775 4118

CFTR-3849-

- GUUGACUUGUCAUCUUGAUUU 21

776 4119

CFTR-3849-

- AGUUGACUUGUCAUCUUGAUUU 22

777 4120

CFTR-3849-

- CAGUUGACUUGUCAUCUUGAUUU 23

778 4121

CFTR-3849-

- UCAGUUGACUUGUCAUCUUGAUUU 24

779 4122

CFTR-3849-

- UGUCUUAAAAGCUUAUUU 18

780 4123

CFTR-3849-

- AUGUCUUAAAAGCUUAUUU 19

781 4124

CFTR-3849-

- UAUGUCUUAAAAGCUUAUUU 20

782 4125

CFTR-3849-

- GUAUGUCUUAAAAGCUUAUUU 21

783 4126

CFTR-3849-

- GGUAUGUCUUAAAAGCUUAUUU 22

784 4127

CFTR-3849-

- GGGUAUGUCUUAAAAGCUUAUUU 23

785 4128

CFTR-3849-

- AGGGUAUGUCUUAAAAGCUUAUUU 24

786 4129

CFTR-3849-

- AAAUUUUAGUAUUUUUUU 18

787 4130

CFTR-3849-

- AAAAUUUUAGUAUUUUUUU 19

788 4131

CFTR-3849-

- AAAAAUUUUAGUAUUUUUUU 20

789 4132

CFTR-3849-

- UAAAAAUUUUAGUAUUUUUUU 21

790 4133

417

5535.1 CFTR-3849-

- CUAAAAAU UUUAGUAUUUUUUU 22

791 4134

CFTR-3849-

- UCUAAAAAUUUUAGUAUUUUUUU 23

792 4135

CFTR-3849-

- CUCUAAAAAUUUUAGUAUUUUUUU 24

793 4136

Table 36A provides exemplary targeting domains for correcting a mutation (e.g., 3849+10kbC->T) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within 500 bp from a mutation (e.g., 3849+10kbC->T), have a high level of orthogonality and start with a 5'G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 36A

Table 36B provides exemplary targeting domains for correcting a mutation (e.g., 3849+10kbC->T) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within 500 bp from a mutation (e.g., 3849+10kbC->T) and have a high level of orthogonality. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 36B

418

5535.1 2nd Tier

Target Site

gRNA Name DNA Strand Targeting Domain

Length Seq ID

CFTR-3849-803 + UAGAGUACUUCCCGCAA 17 4146

CFTR-3849-804 + AUAUACCAUAUGAGGAA 17 4147

CFTR-3849-13 + UGAAAU U U AG AU CCACA 17 3356

CFTR-3849-805 - UUUCAGUUGACUUGUCA 17 4148

CFTR-3849-806 + ACAUAGUAUUGAGAAUA 17 4149

CFTR-3849-807 - U AACU U U CAACAU AU U A 17 4150

CFTR-3849-808 - CUUUGUUGGGUACAAAC 17 4151

CFTR-3849-809 - AACCU U UAAAGCUAAAC 17 4152

CFTR-3849-810 - CACAGUACUGGAUAGUC 17 4153

CFTR-3849-811 + AAUUUGUAAAUCUUUGG 17 4154

CFTR-3849-812 + UUUAGGUGUUUGUGCUG 17 4155

CFTR-3849-813 - UACUUUUGGAUGAACUU 17 4156

CFTR-3849-814 + CACAU AAU AAU U AG U U U 17 4157

CFTR-3849-815 + ACAAUAUACCAUAUGAGGAA 20 4158

CFTR-3849-112 + AACUG AAAU U U AG AU CCACA 20 3455

CFTR-3849-816 - AAAUUUCAGUUGACUUGUCA 20 4159

CFTR-3849-817 - AGACUUUGUUGGGUACAAAC 20 4160

CFTR-3849-818 - U AAAACCU U UAAAGCUAAAC 20 4161

CFTR-3849-819 - UAUCACAGUACUGGAUAGUC 20 4162

CFTR-3849-820 + UAUGAGGAAUUUUGAUUAAG 20 4163

CFTR-3849-821 - AUAGAGAUAUAUGAA CACAU 20 4164

CFTR-3849-822 + AUAUGCUGCUUAUACCCACU 20 4165

CFTR-3849-823 - CUAUACUUUUGGAUGAACUU 20 4166

CFTR-3849-824 - UUAGAUUUAGGGUAUGUCUU 20 4167

CFTR-3849-529 + UGGCACAUAAUAAUUAGUUU 20 3872

Table 36C provides exemplary targeting domains for correcting a mutation (e.g., 3849+10kbC->T) in the CFTR gene selected according to the third tier parameters. The targeting domains bind within 500 bp from a mutation (e.g., 3849+10kbC->T) and start with a 5'G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 36C

419

5535.1 Length

CFTR-3849-825 - GAAAUAAU U UAUAAGAAUAU 20 4168

Table 36D provides exemplary targeting domains for correcting a mutation (e.g., 3849+10kbC->T) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within 500 bp from a mutation (e.g., 3849+10kbC->T). It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 36D

Table 37A provides exemplary targeting domains for correcting a mutation (e.g., 3272- 26->G) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within intron 2, have a high level of orthogonality and start with a 5'G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 37A

420

5535.1 CFTR-lntron2-4 + GACUAUGAGUGGCCCAA 17 15104

CFTR-lntron2-5 - GCCUUGCUCUCUAGGAA 17 15105

CFTR-lntron2-6 + GCUCUAAAUCACUCUAA 17 15106

CFTR-lntron2-7 - GGGAAGUCUUAAGGUAA 17 15107

CFTR-lntron2-8 + G U U ACCAU AAG UAAACA 17 15108

CFTR-lntron2-9 + GCAAAGAGUUCUAACCA 17 15109

CFTR-lntron2-

- GGAACUCAAUGGGACCA 17

10 15110

CFTR-lntron2-

- GCUCAAUUUUGUGACCA 17

11 15111

CFTR-lntron2-

+ GCCAGGGUCACUUCCCA 17

12 15112

CFTR-lntron2-

+ GUAGAGGAUUCAAUCCA 17

13 15113

CFTR-lntron2-

+ GACCUCAGCUGGAAUCA 17

14 15114

CFTR-lntron2-

+ GUAGUUACCUGAGGAGA 17

15 15115

CFTR-lntron2-

- GGAGAAGCAUGUGGGGA 17

16 15116

CFTR-lntron2-

+ GUCCCAUUGAGUUCCUA 17

17 15117

CFTR-lntron2-

- GCAAAUGCCAUGAGGUA 17

18 15118

CFTR-lntron2-

+ GAGGUCUCUAGUGACCC 17

19 15119

CFTR-lntron2-

+ GCAAUACAGACCUCAGC 17

20 15120

CFTR-lntron2-

- GAAACCUGUAGCAUUGC 17

21 15121

CFTR-lntron2-

+ GAUUCAUGUUCUCUAUC 17

22 15122

CFTR-lntron2-

- GAAUUUGCAGAAUUAUC 17

23 15123

CFTR-lntron2-

- GACCUUGCCUUCUCCUC 17

24 15124

CFTR-lntron2-

- GUUCCAAGAUUGUAGUC 17

25 15125

CFTR-lntron2-

+ G G U U C A A U G U G A A A A AG 17

26 15126

CFTR-lntron2-

+ GUAAUAGGCCGGGGCAG 17

27 15127

CFTR-lntron2- + GCUUUACGUUUCAUCAG 17 15128

421

5535.1 28

CFTR-lntron2-

+ GAGAGAUUCUUUAUGGG 17

29 15129

CFTR-lntron2-

- GAUCUGGGCCUGGUAUG 17

30 15130

CFTR-lntron2-

- GGCCUUAGGAACUCAAU 17

31 15131

CFTR-lntron2-

- GGUAACUUGACAGUAAU 17

32 15132

CFTR-lntron2-

+ GAUCCUAACCUUUUGAU 17

33 15133

CFTR-lntron2-

+ GUGAAACUUGAACAACU 17

34 15134

CFTR-lntron2-

- GAACUAUGUGAAGACCU 17

35 15135

CFTR-lntron2-

+ GGUGGCAUUUGAGUCCU 17

36 15136

CFTR-lntron2-

- GUAUUGCCUUGCUCUCU 17

37 15137

CFTR-lntron2-

- GAAUGAU U AAU CAG AG U 17

38 15138

CFTR-lntron2-

+ GGUGAUGUGGUUCUAGU 17

39 15139

CFTR-lntron2-

- GGUGGAGAACUGGCCUU 17

40 15140

CFTR-lntron2-

- GAGUGACAUACCAUUUU 17

41 15141

CFTR-lntron2-

+ GCCUUCAAAAUGCCAAAAAA 20

42 15142

CFTR-lntron2-

+ GAGGUACAAAGUACCAAAAA 20

43 15143

CFTR-lntron2-

+ G UG U ACAU AAACCAACAAAA 20

44 15144

CFTR-lntron2-

- GGUAAUUAGGCUUUAUAGAA 20

45 15145

CFTR-lntron2-

+ GCAAUGUAGUUUUAGGAACA 20

46 15146

CFTR-lntron2-

+ GGAGCAAAGAGUUCUAACCA 20

47 15147

CFTR-lntron2-

+ GAAGCCAGGGUCACUUCCCA 20

48 15148

CFTR-lntron2-

+ GGAUUUUUCACAUUUAGCCA 20

49 15149

422

5535.1 CFTR-lntron2-

- GAUUCACACUUCUAAGAUCA 20

50 15150

CFTR-lntron2-

- GCCCUCAAGUGGUUGCCAGA 20

51 15151

CFTR-lntron2-

+ GGGGUAGUUACCUGAGGAGA 20

52 15152

CFTR-lntron2-

- GGUGGAGAAGCAUGUGGGGA 20

53 15153

CFTR-lntron2-

- GAGUAACCAAAUGUUAUGGA 20

54 15154

CFTR-lntron2-

- GGGAAUGAUUAAUCAGAGUA 20

55 15155

CFTR-lntron2-

- GUACUCCCUGGGAAGUCUUA 20

56 15156

CFTR-lntron2-

+ GGAAACUGAGAGAUUCUUUA 20

57 15157

CFTR-lntron2-

- GAGUCUCGUGCCAACAGCAC 20

58 15158

CFTR-lntron2-

+ GUAAAUUGGGUUUCUGUCAC 20

59 15159

CFTR-lntron2-

+ GAAAGUGAAG U AG AG AG ACC 20

60 15160

CFTR-lntron2-

- GCACCCUUGGGAAGUGACCC 20

61 15161

CFTR-lntron2-

- GCUAACAUUCUCUGCUCUCC 20

62 15162

CFTR-lntron2-

+ GUUAAUGUUCUUCAACCAUC 20

63 15163

CFTR-lntron2-

- GACCAGCU U U CU ACAU AAAG 20

64 15164

CFTR-lntron2-

+ GUGUUGUUAUAUUUCAUAAG 20

65 15165

CFTR-lntron2-

+ GGAGUAAUAGGCCGGGGCAG 20

66 15166

CFTR-lntron2-

+ GUCACUUCCCAAGGGUGCAG 20

67 15167

CFTR-lntron2-

- GAUAAAAGGGUGAGUGAAGG 20

68 15168

CFTR-lntron2-

- GAACUAUGUGAAGACCUAGG 20

69 15169

CFTR-lntron2-

- GUUUACCUAGUUCUUCCUUG 20

70 15170

CFTR-lntron2- + GGUCGGGGAAUUUCUUUAAU 20 15171

423

5535.1 71

CFTR-lntron2-

+ GUCACAAAAUUGAGCCAGAU 20

72 15172

CFTR-lntron2-

+ GAAACUGAGAGAUUCUUUAU 20

73 15173

CFTR-lntron2-

- GAGUCAUAGUGCUUACCCCU 20

74 15174

CFTR-lntron2-

- GCUCUCAUUAGCAAGCUUCU 20

75 15175

CFTR-lntron2-

+ GUAGGUGAUGUGGUUCUAGU 20

76 15176

CFTR-lntron2-

- GAAGAGUGACAUACCAUUUU 20

77 15177

Table 37B provides exemplary targeting domains for correcting a mutation (e.g., 3272- 26->G) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within intron 2 and have a high level of orthogonality. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through

complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 37B

424

5535.1 CFTR-lntron2-

- UGGCCUUAGGAACUCAA 17

85 15185

CFTR-lntron2-

+ CCAGGCCCAGAUCAGAA 17

86 15186

CFTR-lntron2-

- AAUUAGGCUUUAUAGAA 17

87 15187

CFTR-lntron2-

+ ACGGAAGUAAUGUAGAA 17

88 15188

CFTR-lntron2-

+ UAACCUUUUGAUUGGAA 17

89 15189

CFTR-lntron2-

+ UGACUACAAUCUUGGAA 17

90 15190

CFTR-lntron2-

+ CACGAUUUACUUCAUAA 17

91 15191

CFTR-lntron2-

- UGGUAACUUGACAGUAA 17

92 15192

CFTR-lntron2-

+ UCGGGGAAUUUCUUUAA 17

93 15193

CFTR-lntron2-

+ AUGUAGUUUUAGGAACA 17

94 15194

CFTR-lntron2-

+ AAAU U U CAUG AACCACA 17

95 15195

CFTR-lntron2-

+ U GAAAAAG U GG U CC ACA 17

96 15196

CFTR-lntron2-

+ UGAGGGCCAUGGUCACA 17

97 15197

CFTR-lntron2-

- UAACUGCCUUGUGACCA 17

98 15198

CFTR-lntron2-

+ AGACUAUGAGUGGCCCA 17

99 15199

CFTR-lntron2-

- UAAAACUACAUUGCCCA 17

100 15200

CFTR-lntron2-

+ UACCUUAAGACUUCCCA 17

101 15201

CFTR-lntron2-

+ UUUUUCACAUUUAGCCA 17

102 15202

CFTR-lntron2-

+ CAACCACUUGAGGGCCA 17

103 15203

CFTR-lntron2-

+ CUGGCAAUCUCUAAGCA 17

104 15204

CFTR-lntron2-

+ ACCAUUCCUAGAGAGCA 17

105 15205

CFTR-lntron2- + UACCUGAGGAGAAGGCA 17 15206

425

5535.1 106

CFTR-lntron2-

- UCACACUUCUAAGAUCA 17

107 15207

CFTR-lntron2-

+ AAAGUAUCCCUACCUCA 17

108 15208

CFTR-lntron2-

+ UCACAAAAUCCAUCUCA 17

109 15209

CFTR-lntron2-

- UUAAGGACCACGAAAGA 17

110 15210

CFTR-lntron2-

- CUCAAGUGGUUGCCAGA 17

111 15211

CFTR-lntron2-

+ ACCAGGCCCAGAUCAGA 17

112 15212

CFTR-lntron2-

- UAAUUAGGCUUUAUAGA 17

113 15213

CFTR-lntron2-

- UAACCAAAUGUUAUGGA 17

114 15214

CFTR-lntron2-

- UGCCAGUUAAUGAAUGA 17

115 15215

CFTR-lntron2-

+ AUCUGGCAACCACUUGA 17

116 15216

CFTR-lntron2-

- UCAUUAGCAAGCUUCUA 17

117 15217

CFTR-lntron2-

- UCUCAGCUCCUGAAGUA 17

118 15218

CFTR-lntron2-

- AAUGAUUAAUCAGAGUA 17

119 15219

CFTR-lntron2-

- AGAGCCAUGUUUACUUA 17

120 15220

CFTR-lntron2-

- CUCCCUGGGAAGUCUUA 17

121 15221

CFTR-lntron2-

- UGAGUAACCAAAUGUUA 17

122 15222

CFTR-lntron2-

- CUUUGCUCCUAUCUUUA 17

123 15223

CFTR-lntron2-

+ AACUGAGAGAUUCUUUA 17

124 15224

CFTR-lntron2-

+ UUAAAUAGUCUGAAAAC 17

125 15225

CFTR-lntron2-

- AGACCUAGGUGGAGAAC 17

126 15226

CFTR-lntron2-

+ UCUACCUGGCAUGUAAC 17

127 15227

426

5535.1 CFTR-lntron2-

+ CUCCAUCAUUCAUUAAC 17

128 15228

CFTR-lntron2-

- UCUCGUGCCAACAGCAC 17

129 15229

CFTR-lntron2-

- CUUAAGGUAAUGGCUAC 17

130 15230

CFTR-lntron2-

+ CUCUCCAGCAAUGCUAC 17

131 15231

CFTR-lntron2-

+ AACGUAUGGGUUUGUAC 17

132 15232

CFTR-lntron2-

+ AGCAAAGAGUUCUAACC 17

133 15233

CFTR-lntron2-

+ AUAAGGCAAAUGCCACC 17

134 15234

CFTR-lntron2-

- AGGACUCAAAUGCCACC 17

135 15235

CFTR-lntron2-

+ AG UG AAG U AG AG AG ACC 17

136 15236

CFTR-lntron2-

+ UAGUAGGACCACAUACC 17

137 15237

CFTR-lntron2-

+ AGAGGAGAUAUUCUACC 17

138 15238

CFTR-lntron2-

- CCCUUGGGAAGUGACCC 17

139 15239

CFTR-lntron2-

- CUAAAACUACAUUGCCC 17

140 15240

CFTR-lntron2-

- AAUACAAAUGUACUCCC 17

141 15241

CFTR-lntron2-

- UACAUAAAGUGGGUCCC 17

142 15242

CFTR-lntron2-

+ UUACCUUAAGACUUCCC 17

143 15243

CFTR-lntron2-

+ UUAUGAAAUGUGAAGCC 17

144 15244

CFTR-lntron2-

+ UAAAGGAGUAAUAGGCC 17

145 15245

CFTR-lntron2-

- CAUGCUUAGAGAUUGCC 17

146 15246

CFTR-lntron2-

+ ACUUAGAUAUUCAAAGC 17

147 15247

CFTR-lntron2-

+ CACUUUAUGUAGAAAGC 17

148 15248

CFTR-lntron2- + UGUUCAAUAAUAGAAGC 17 15249

427

5535.1 149

CFTR-lntron2-

- U A A U AAA U AC A A U C AG C 17

150 15250

CFTR-lntron2-

+ CUAAAGGAGUAAUAGGC 17

151 15251

CFTR-lntron2-

- AUUAAUCAGAGUAGGGC 17

152 15252

CFTR-lntron2-

- UGGCAUUUGCCUUAUGC 17

153 15253

CFTR-lntron2-

- UAAACAUAAUCCAUUGC 17

154 15254

CFTR-lntron2-

+ AAUGUUCUUCAACCAUC 17

155 15255

CFTR-lntron2-

+ CCCUUUUAUCUGGCAUC 17

156 15256

CFTR-lntron2-

- AAGAACAUUAACCUAUC 17

157 15257

CFTR-lntron2-

+ UCACUCACCCUUUUAUC 17

158 15258

CFTR-lntron2-

+ UAUGACUCAAGAGUCUC 17

159 15259

CFTR-lntron2-

+ UAUGUAGAAAGCUGGUC 17

160 15260

CFTR-lntron2-

+ AGGUCUUCACAUAGUUC 17

161 15261

CFTR-lntron2-

- CAGCUUUCUACAUAAAG 17

162 15262

CFTR-lntron2-

+ ACUAUGAGUGGCCCAAG 17

163 15263

CFTR-lntron2-

- UGACCAUGGCCCUCAAG 17

164 15264

CFTR-lntron2-

+ UUGUUAUAUUUCAUAAG 17

165 15265

CFTR-lntron2-

+ ACUUCCCAAGGGUGCAG 17

166 15266

CFTR-lntron2-

+ AUGCUUUCCACUCAGAG 17

167 15267

CFTR-lntron2-

+ UCAUUCUAGACUAUGAG 17

168 15268

CFTR-lntron2-

- U C A A AG A A U U A AG C U AG 17

169 15269

CFTR-lntron2-

- CAUUAGCAAGCUUCUAG 17

170 15270

428

5535.1 CFTR-lntron2-

+ ACACUGCAGUUAUGUAG 17

171 15271

CFTR-lntron2-

+ AAAGGAGUAAUAGGCCG 17

172 15272

CFTR-lntron2-

+ AGGAGAAGGCAAGGUCG 17

173 15273

CFTR-lntron2-

+ AAGGGCUCCUUCUUUCG 17

174 15274

CFTR-lntron2-

- CUAUGUGAAGACCUAGG 17

175 15275

CFTR-lntron2-

+ AGAGAUUCUUUAUGGGG 17

176 15276

CFTR-lntron2-

- UGGAGAAGCAUGUGGGG 17

177 15277

CFTR-lntron2-

- CAAAUGUUAUGGAUGGG 17

178 15278

CFTR-lntron2-

+ UAGUUUUAGGAACAUGG 17

179 15279

CFTR-lntron2-

+ UGAGAGAUUCUUUAUGG 17

180 15280

CFTR-lntron2-

- ACUCAAAUGCCACCUGG 17

181 15281

CFTR-lntron2-

+ UAAAUUGAAUCAACAUG 17

182 15282

CFTR-lntron2-

- UGUGUGCAAAUGCCAUG 17

183 15283

CFTR-lntron2-

- AAAGGUGGAGAAGCAUG 17

184 15284

CFTR-lntron2-

+ AAUGGGGUAGUUACCUG 17

185 15285

CFTR-lntron2-

- AGCCAUGAUUCCAGCUG 17

186 15286

CFTR-lntron2-

- UCUACAUUACUUCCGUG 17

187 15287

CFTR-lntron2-

+ AUCUUGGAACGGAUGUG 17

188 15288

CFTR-lntron2-

+ CAUCUGGCAACCACUUG 17

189 15289

CFTR-lntron2-

+ CCUAUUCUAGGCACUUG 17

190 15290

CFTR-lntron2-

- UACCUAGUUCUUCCUUG 17

191 15291

CFTR-lntron2- - UUGGUGCUAACAAUUUG 17 15292

429

5535.1 192

CFTR-lntron2-

+ UACUUAAGCUAGUAAAU 17

193 15293

CFTR-lntron2-

- CCCCAAGUGCCUAGAAU 17

194 15294

CFTR-lntron2-

+ CACUCUAAAGGAGUAAU 17

195 15295

CFTR-lntron2-

+ CGGGGAAUUUCUUUAAU 17

196 15296

CFTR-lntron2-

+ UCGUGGUCCUUAAAGAU 17

197 15297

CFTR-lntron2-

+ ACAAAAUUGAGCCAGAU 17

198 15298

CFTR-lntron2-

- UGGGGAGGGAAAUAGAU 17

199 15299

CFTR-lntron2-

- AACCAAAUGUUAUGGAU 17

200 15300

CFTR-lntron2-

+ AAAAU AAU AG AACG U AU 17

201 15301

CFTR-lntron2-

- AAAAGG AACG AAU U U AU 17

202 15302

CFTR-lntron2-

+ ACUGAGAGAUUCUUUAU 17

203 15303

CFTR-lntron2-

+ AACCACAAGGAAGAACU 17

204 15304

CFTR-lntron2-

- AUAGUCUAGAAUGAACU 17

205 15305

CFTR-lntron2-

+ AGGCCAGUUCUCCACCU 17

206 15306

CFTR-lntron2-

- UUGUACCUCUGCACCCU 17

207 15307

CFTR-lntron2-

+ AGGUCUCUAGUGACCCU 17

208 15308

CFTR-lntron2-

- UCAUAGUGCUUACCCCU 17

209 15309

CFTR-lntron2-

- AUACAAAUGUACUCCCU 17

210 15310

CFTR-lntron2-

- UGUACACACCCCUUCCU 17

211 15311

CFTR-lntron2-

+ CUUAGAUAUUCAAAGCU 17

212 15312

CFTR-lntron2-

- UUAAUCAGAGUAGGGCU 17

213 15313

430

5535.1 CFTR-lntron2-

+ UAUCCUGACUACAAUCU 17

214 15314

CFTR-lntron2-

+ UCUCUAAGCAUGGAUCU 17

215 15315

CFTR-lntron2-

- ACCACAUCACCUACUCU 17

216 15316

CFTR-lntron2-

+ AUGACUCAAGAGUCUCU 17

217 15317

CFTR-lntron2-

- CUCAUUAGCAAGCUUCU 17

218 15318

CFTR-lntron2-

+ U UG U U AG CACCAAG AG U 17

219 15319

CFTR-lntron2-

- CAAAGAAU U AAG CU AG U 17

220 15320

CFTR-lntron2-

- AAGGUGGAGAAGCAUGU 17

221 15321

CFTR-lntron2-

+ CAUCAGGCCUGUGCUGU 17

222 15322

CFTR-lntron2-

- CAUUGAACCCAUUUUGU 17

223 15323

CFTR-lntron2-

+ ACUUAAGCUAGUAAAUU 17

224 15324

CFTR-lntron2-

+ CUCCCAUCCAUAACAUU 17

225 15325

CFTR-lntron2-

- UGUACCUCUGCACCCUU 17

226 15326

CFTR-lntron2-

- CAUAGUGCUUACCCCUU 17

227 15327

CFTR-lntron2-

- U U U CC AAU CAAAAG G U U 17

228 15328

CFTR-lntron2-

- AGGCCUGAUGCCAGAUAAAA 20

229 15329

CFTR-lntron2-

+ CUUCUCCAU C A A AG GAG AAA 20

230 15330

CFTR-lntron2-

- AUCCAUGAUGGAAUGUGAAA 20

231 15331

CFTR-lntron2-

- CAGGCCUGAUGCCAGAUAAA 20

232 15332

CFTR-lntron2-

+ AGCCUUUUUUCUCUUCACAA 20

233 15333

CFTR-lntron2-

+ CUAGGUAAACAAUUAGACAA 20

234 15334

CFTR-lntron2- + U CACAU U U AGCCAAGG ACAA 20 15335

431

5535.1 235

CFTR-l ntron2-

+ CUAGACUAUGAGUGGCCCAA 20

236 15336

CFTR-l ntron2-

+ AAGCCAGGGUCACUUCCCAA 20

237 15337

CFTR-l ntron2-

+ ACU UGUCAAUAUACCUGCAA 20

238 15338

CFTR-l ntron2-

+ AGACUCACCUUCUCCAUCAA 20

239 15339

CFTR-l ntron2-

- AUUCACACUUCUAAGAUCAA 20

240 15340

CFTR-l ntron2-

- AACUGGCCUUAGGAACUCAA 20

241 15341

CFTR-l ntron2-

+ AUACCAGGCCCAGAUCAGAA 20

242 15342

CFTR-l ntron2-

- UAGCUCUGUGUGUGAGAGAA 20

243 15343

CFTR-l ntron2-

+ CACACGGAAGUAAUGUAGAA 20

244 15344

CFTR-l ntron2-

- AUUGCCUUGCUCUCUAGGAA 20

245 15345

CFTR-l ntron2-

+ UCCUAACCUUUUGAUUGGAA 20

246 15346

CFTR-l ntron2-

+ UCCUGACUACAAUCUUGGAA 20

247 15347

CFTR-l ntron2-

- CAGAUAAAAGGGUGAGUGAA 20

248 15348

CFTR-l ntron2-

+ AUACACGAUUUACUUCAUAA 20

249 15349

CFTR-l ntron2-

+ AUGGCUCUAAAUCACUCUAA 20

250 15350

CFTR-l ntron2-

- UUAUGGUAACUUGACAGUAA 20

251 15351

CFTR-l ntron2-

- CCUGGGAAGUCUUAAGGUAA 20

252 15352

CFTR-l ntron2-

+ CUACUAAAAUCAUGUAUUAA 20

253 15353

CFTR-l ntron2-

+ AGGUCGGGGAAUUUCUUUAA 20

254 15354

CFTR-l ntron2-

+ CAAG U U ACCAU AAG UAAACA 20

255 15355

CFTR-l ntron2-

+ AUGUGAAAAAGUGGUCCACA 20

256 15356

432

5535.1 CFTR-l ntron2-

+ ACU UGAGGGCCAUGGUCACA 20

257 15357

CFTR-l ntron2-

- UUAGGAACUCAAUGGGACCA 20

258 15358

CFTR-l ntron2-

- UCAUAACUGCCUUGUGACCA 20

259 15359

CFTR-l ntron2-

- CUGGCUCAAUUUUGUGACCA 20

260 15360

CFTR-l ntron2-

+ UCUAGACUAUGAGUGGCCCA 20

261 15361

CFTR-l ntron2-

- UCCUAAAACUACAUUGCCCA 20

262 15362

CFTR-l ntron2-

+ CAUUACCUUAAGACUUCCCA 20

263 15363

CFTR-l ntron2-

+ AGUUAUGAAAUGUGAAGCCA 20

264 15364

CFTR-l ntron2-

+ UGGCAACCACUUGAGGGCCA 20

265 15365

CFTR-l ntron2-

+ UAUGUAGAGGAUUCAAUCCA 20

266 15366

CFTR-l ntron2-

+ AGCCUGGCAAUCUCUAAGCA 20

267 15367

CFTR-l ntron2-

+ ACUACCAUUCCUAGAGAGCA 20

268 15368

CFTR-l ntron2-

+ AGUUACCUGAGGAGAAGGCA 20

269 15369

CFTR-l ntron2-

+ ACAGACCUCAGCUGGAAUCA 20

270 15370

CFTR-l ntron2-

+ AGCCAUUUCACAUUCCAUCA 20

271 15371

CFTR-l ntron2-

+ AACAAAGUAUCCCUACCUCA 20

272 15372

CFTR-l ntron2-

+ U UUUCACAAAAUCCAUCUCA 20

273 15373

CFTR-l ntron2-

- UCUUUAAGGACCACGAAAGA 20

274 15374

CFTR-l ntron2-

+ CAUACCAGGCCCAGAUCAGA 20

275 15375

CFTR-l ntron2-

+ CAAAGGAGAAAUGGAUCAGA 20

276 15376

CFTR-l ntron2-

- UCUUAUUAGAGACCAUGAGA 20

277 15377

CFTR-l ntron2- - CAUGUGGGGAGGGAAAUAGA 20 15378

433

5535.1 278

CFTR-lntron2-

- AGGUAAUUAGGCUUUAUAGA 20

279 15379

CFTR-lntron2-

+ UCAGAUGGGAAAGCCAAGGA 20

280 15380

CFTR-lntron2-

- CUUUGCCAGUUAAUGAAUGA 20

281 15381

CFTR-lntron2-

- AAGUUUUAAUUGGAUGCUGA 20

282 15382

CFTR-lntron2-

- CCAGAUAAAAGGGUGAGUGA 20

283 15383

CFTR-lntron2-

+ ACCAUCUGGCAACCACUUGA 20

284 15384

CFTR-lntron2-

- CUGAUCCAUUUCUCCUUUGA 20

285 15385

CFTR-lntron2-

- UCCUUUUUUUGGCAUUUUGA 20

286 15386

CFTR-lntron2-

+ UCAGAGUAAGAAGCU AAA U A 20

287 15387

CFTR-lntron2-

- AUCCCCAAGUGCCUAGAAUA 20

288 15388

CFTR-lntron2-

+ UUGGUCCCAUUGAGUUCCUA 20

289 15389

CFTR-lntron2-

- CUCUCAUUAGCAAGCUUCUA 20

290 15390

CFTR-lntron2-

- ACAUCUCAGCUCCUGAAGUA 20

291 15391

CFTR-lntron2-

- UGUGCAAAUGCCAUGAGGUA 20

292 15392

CFTR-lntron2-

- UUUAGAGCCAUGUUUACUUA 20

293 15393

CFTR-lntron2-

- CUCUGAGUAACCAAAUGUUA 20

294 15394

CFTR-lntron2-

- ACUCUUUGCUCCUAUCUUUA 20

295 15395

CFTR-lntron2-

+ ACAU U AAAU AG UCUGAAAAC 20

296 15396

CFTR-lntron2-

+ AUGGGGGAUACAGUGAAAAC 20

297 15397

CFTR-lntron2-

- UGAAGACCUAGGUGGAGAAC 20

298 15398

CFTR-lntron2-

+ UAUUCUACCUGGCAUGUAAC 20

299 15399

434

5535.1 CFTR-lntron2-

+ UGGCUCCAUCAUUCAUUAAC 20

300 15400

CFTR-lntron2-

- CUGGUUUUAUUUUCUCAGAC 20

301 15401

CFTR-lntron2-

- AGUCUUAAGGUAAUGGCUAC 20

302 15402

CFTR-lntron2-

+ UAUCUCUCCAGCAAUGCUAC 20

303 15403

CFTR-lntron2-

+ UAGAACGUAUGGGUUUGUAC 20

304 15404

CFTR-lntron2-

+ AGG AGCAAAG AG U U CU AACC 20

305 15405

CFTR-lntron2-

+ AGCAUAAGGCAAAUGCCACC 20

306 15406

CFTR-lntron2-

- CCAAGGACUCAAAUGCCACC 20

307 15407

CFTR-lntron2-

+ UUCUAGUAGGACCACAUACC 20

308 15408

CFTR-lntron2-

+ CUGAGAGGAGAUAUUCUACC 20

309 15409

CFTR-lntron2-

+ UAAGAGGUCUCUAGUGACCC 20

310 15410

CFTR-lntron2-

- UUCCUAAAACUACAUUGCCC 20

311 15411

CFTR-lntron2-

- UUGAAUACAAAUGUACUCCC 20

312 15412

CFTR-lntron2-

- UUCUACAUAAAGUGGGUCCC 20

313 15413

CFTR-lntron2-

+ CCAUUACCUUAAGACUUCCC 20

314 15414

CFTR-lntron2-

+ CAGUUAUGAAAUGUGAAGCC 20

315 15415

CFTR-lntron2-

- CUUCCCUUCUGAUCUGGGCC 20

316 15416

CFTR-lntron2-

- AUCCAUGCUUAGAGAUUGCC 20

317 15417

CFTR-lntron2-

+ AAAACUUAGAUAUUCAAAGC 20

318 15418

CFTR-lntron2-

+ ACCCACUUUAUGUAGAAAGC 20

319 15419

CFTR-lntron2-

+ AAGUGUUCAAUAAUAGAAGC 20

320 15420

CFTR-lntron2- - ACUUAAUAAAUACAAUCAGC 20 15421

435

5535.1 321

CFTR-l ntron2-

+ AAGGCAAUACAGACCUCAGC 20

322 15422

CFTR-l ntron2-

- AUGAUUAAUCAGAGUAGGGC 20

323 15423

CFTR-l ntron2-

- AUAUAAACAUAAUCCAUUGC 20

324 15424

CFTR-l ntron2-

- AUAGAAACCUGUAGCAU UGC 20

325 15425

CFTR-l ntron2-

- AAACUUCUUCCCUUCUGAUC 20

326 15426

CFTR-l ntron2-

- UUGAAGAACAUUAACCUAUC 20

327 15427

CFTR-l ntron2-

+ UCAGAUUCAUGUUCUCUAUC 20

328 15428

CFTR-l ntron2-

- UCUGAAUUUGCAGAAU UAUC 20

329 15429

CFTR-l ntron2-

- CCCGACCUUGCCUUCUCCUC 20

330 15430

CFTR-l ntron2-

+ CACUAUGACUCAAGAGUCUC 20

331 15431

CFTR-l ntron2-

- UCCGUUCCAAGAUUGUAGUC 20

332 15432

CFTR-l ntron2-

+ CCUGAGGAGAAGGCAAGGUC 20

333 15433

CFTR-l ntron2-

+ CUUUAUGUAGAAAGCUGGUC 20

334 15434

CFTR-l ntron2-

+ CCUAGGUCUUCACAUAGUUC 20

335 15435

CFTR-l ntron2-

+ AUGGGUUCAAUGUGAAAAAG 20

336 15436

CFTR-l ntron2-

+ UAGACUAUGAGUGGCCCAAG 20

337 15437

CFTR-l ntron2-

- UUGUGACCAUGGCCCUCAAG 20

338 15438

CFTR-l ntron2-

- CU U U CAU U AACAG AAAU CAG 20

339 15439

CFTR-l ntron2-

+ AAGGCUUUACGUUUCAUCAG 20

340 15440

CFTR-l ntron2-

+ AUGAUGCUUUCCACUCAGAG 20

341 15441

CFTR-l ntron2-

+ AGUUCAUUCUAGACUAUGAG 20

342 15442

436

5535.1 CFTR-lntron2-

+ UUCCACUCAGAGUGGCUGAG 20

343 15443

CFTR-lntron2-

- CUCCUCUCAGCCACUCUGAG 20

344 15444

CFTR-lntron2-

- UAUUCAAAGAAUUAAGCUAG 20

345 15445

CFTR-lntron2-

- UCUCAUUAGCAAGCUUCUAG 20

346 15446

CFTR-lntron2-

+ UGCACACUGCAGUUAUGUAG 20

347 15447

CFTR-lntron2-

+ UCUAAAGGAGUAAUAGGCCG 20

348 15448

CFTR-lntron2-

+ CUGAGGAGAAGGCAAGGUCG 20

349 15449

CFTR-lntron2-

+ AUAAGGCAAAUGCCACCAGG 20

350 15450

CFTR-lntron2-

+ CUGAGAGAUUCUUUAUGGGG 20

351 15451

CFTR-lntron2-

- AACCAAAUGUUAUGGAUGGG 20

352 15452

CFTR-lntron2-

+ ACUGAGAGAUUCUUUAUGGG 20

353 15453

CFTR-lntron2-

+ UUUAAAUUGAAUCAACAUGG 20

354 15454

CFTR-lntron2-

+ AUGUAGUUUUAGGAACAUGG 20

355 15455

CFTR-lntron2-

+ AACUGAGAGAUUCUUUAUGG 20

356 15456

CFTR-lntron2-

- AGGACUCAAAUGCCACCUGG 20

357 15457

CFTR-lntron2-

+ UUUUAAAUUGAAUCAACAUG 20

358 15458

CFTR-lntron2-

+ AGCACCAAGAGUAGGUGAUG 20

359 15459

CFTR-lntron2-

- UCUGAUCUGGGCCUGGUAUG 20

360 15460

CFTR-lntron2-

+ AAACUGAGAGAUUCUUUAUG 20

361 15461

CFTR-lntron2-

+ UAGAAUGGGGUAGUUACCUG 20

362 15462

CFTR-lntron2-

- UGGAGCCAUGAUUCCAGCUG 20

363 15463

CFTR-lntron2- - UAAGUUUUAAUUGGAUGCUG 20 15464

437

5535.1 364

CFTR-lntron2-

- CUUUCUACAUUACUUCCGUG 20

365 15465

CFTR-lntron2-

+ ACAAUCUUGGAACGGAUGUG 20

366 15466

CFTR-lntron2-

+ AACCAUCUGGCAACCACUUG 20

367 15467

CFTR-lntron2-

- CUCUUGGUGCUAACAAUUUG 20

368 15468

CFTR-lntron2-

+ UGUACAUAAACCAACAAAAU 20

369 15469

CFTR-lntron2-

+ AUUUACUUAAGCUAGUAAAU 20

370 15470

CFTR-lntron2-

- ACUGGCCUUAGGAACUCAAU 20

371 15471

CFTR-lntron2-

- CAAGUUCAAAAUAAUAUAAU 20

372 15472

CFTR-lntron2-

- UAUGGUAACUUGACAGUAAU 20

373 15473

CFTR-lntron2-

+ AAUCACUCUAAAGGAGUAAU 20

374 15474

CFTR-lntron2-

+ CUUUCGUGGUCCUUAAAGAU 20

375 15475

CFTR-lntron2-

+ AAAGGAGAAAUGGAUCAGAU 20

376 15476

CFTR-lntron2-

- AUGUGGGGAGGGAAAUAGAU 20

377 15477

CFTR-lntron2-

- AGUAACCAAAUGUUAUGGAU 20

378 15478

CFTR-lntron2-

+ AAGGAUCCUAACCUUUUGAU 20

379 15479

CFTR-lntron2-

+ ACAAAAAUAAUAGAACGUAU 20

380 15480

CFTR-lntron2-

- AAU AAAAGG AACG AAU U U AU 20

381 15481

CFTR-lntron2-

+ UGGGUGAAACUUGAACAACU 20

382 15482

CFTR-lntron2-

+ AUGAACCACAAGGAAGAACU 20

383 15483

CFTR-lntron2-

- CUCAUAGUCUAGAAUGAACU 20

384 15484

CFTR-lntron2-

- AGCUUCUAUUAUUGAACACU 20

385 15485

438

5535.1 CFTR-lntron2-

+ CUAAGGCCAGUUCUCCACCU 20

386 15486

CFTR-lntron2-

- CCUGAACUAUGUGAAGACCU 20

387 15487

CFTR-lntron2-

+ AAGAGGUCUCUAGUGACCCU 20

388 15488

CFTR-lntron2-

- UGAAUACAAAUGUACUCCCU 20

389 15489

CFTR-lntron2-

+ CCAGGUGGCAUUUGAGUCCU 20

390 15490

CFTR-lntron2-

- AAGAAGGAGCCCUUUGUCCU 20

391 15491

CFTR-lntron2-

- UUAUGUACACACCCCUUCCU 20

392 15492

CFTR-lntron2-

+ AAACUUAGAUAUUCAAAGCU 20

393 15493

CFTR-lntron2-

- UGAUUAAUCAGAGUAGGGCU 20

394 15494

CFTR-lntron2-

+ UCAUAUCCUGACUACAAUCU 20

395 15495

CFTR-lntron2-

+ CAAUCUCUAAGCAUGGAUCU 20

396 15496

CFTR-lntron2-

- AACUUCUUCCCUUCUGAUCU 20

397 15497

CFTR-lntron2-

- AGAACCACAUCACCUACUCU 20

398 15498

CFTR-lntron2-

- UCUGUAUUGCCUUGCUCUCU 20

399 15499

CFTR-lntron2-

+ ACUAUGACUCAAGAGUCUCU 20

400 15500

CFTR-lntron2-

- ACCAGCUUUCUACAUAAAGU 20

401 15501

CFTR-lntron2-

+ AAAUUGUUAGCACCAAGAGU 20

402 15502

CFTR-lntron2-

- AGGGAAUGAUUAAUCAGAGU 20

403 15503

CFTR-lntron2-

- AUUCAAAGAAUUAAGCUAGU 20

404 15504

CFTR-lntron2-

+ ACCUGAGGAGAAGGCAAGGU 20

405 15505

CFTR-lntron2-

- AGAAAGGUGGAGAAGCAUGU 20

406 15506

CFTR-lntron2- + UGGCAUCAGGCCUGUGCUGU 20 15507

439

5535.1 407

CFTR-lntron2-

- UCACAUUGAACCCAUUUUGU 20

408 15508

CFTR-lntron2-

- AUAGAUGGGAAAAGGUAAUU 20

409 15509

CFTR-lntron2-

+ AACCUCCCAUCCAUAACAUU 20

410 15510

CFTR-lntron2-

+ UCAACUCAAUGUUUUUACUU 20

411 15511

CFTR-lntron2-

- CUUUGUACCUCUGCACCCUU 20

412 15512

CFTR-lntron2-

- AGUCAUAGUGCUUACCCCUU 20

413 15513

CFTR-lntron2-

- CUAGGUGGAGAACUGGCCUU 20

414 15514

CFTR-lntron2-

- UCCUUUCCAAUCAAAAGGUU 20

415 15515

CFTR-lntron2-

+ ACCCUGGGCAAUGUAGUUUU 20

416 15516

Table 37C provides exemplary targeting domains for correcting a mutation (e.g., 3272- 26->G) in the CFTR gene selected according to the third tier parameters. The targeting domains bind within intron 2 and start with a 5'G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 37C

440

5535.1 CFTR-lntron2-

- GUUGAAUGAAUCCAUGA 17

422 15522

CFTR-lntron2-

- GAUAAAAGGGUGAGUGA 17

423 15523

CFTR-lntron2-

+ GAGUAAGAAGCUAAAUA 17

424 15524

CFTR-lntron2-

- GAAUAGGGCCUGGCAUA 17

425 15525

CFTR-lntron2-

+ GGGGAUACAGUGAAAAC 17

426 15526

CFTR-lntron2-

- GUUUUAUUUUCUCAGAC 17

427 15527

CFTR-lntron2-

+ GAGAAUCACUUGAACCC 17

428 15528

CFTR-lntron2-

+ GAGAUUCGCUUGAACCC 17

429 15529

CFTR-lntron2-

- GUCUCGCUGUGUCACCC 17

430 15530

CFTR-lntron2-

- GGCGUGAGCCACUGCCC 17

431 15531

CFTR-lntron2-

- GUCUUGCUCUGUUGCCC 17

432 15532

CFTR-lntron2-

+ GG AG U U CAAG ACCAGCC 17

433 15533

CFTR-lntron2-

- GCAUGCACCACCAGGCC 17

434 15534

CFTR-lntron2-

- GUGCCUAGAAUAGGGCC 17

435 15535

CFTR-lntron2-

- GUUUUGCUAUGCUGGCC 17

436 15536

CFTR-lntron2-

- GUUUCGCCAUGUUGGCC 17

437 15537

CFTR-lntron2-

- GCACUCGCCACAAUGCC 17

438 15538

CFTR-lntron2-

+ GAGGAGAAGGCAAGGUC 17

439 15539

CFTR-lntron2-

+ GCAGAUCACUUGAGGUC 17

440 15540

CFTR-lntron2-

+ GGUGGAAACCAUACUUC 17

441 15541

CFTR-lntron2-

+ G A A A AG AAGUAACAGGG 17

442 15542

CFTR-lntron2- - GUUUUAAUUGGAUGCUG 17 15543

441

5535.1 CFTR-lntron2-

+ GGCGGGCAGAUCACUUG 17

444 15544

CFTR-lntron2-

+ GGUGGGCAGAUCACUUG 17

445 15545

CFTR-lntron2-

+ GAAAGAAAAAAUAGAAU 17

446 15546

CFTR-lntron2-

- G U U CAAAAU AAU AU AAU 17

447 15547

CFTR-lntron2-

+ GGAGAAAUGGAUCAGAU 17

448 15548

CFTR-lntron2-

+ GCCCUAUUCUAGGCACU 17

449 15549

CFTR-lntron2-

- GUGGAGUUUCGCCAUGU 17

450 15550

CFTR-lntron2-

- GAUGGGAAAAGGUAAUU 17

451 15551

CFTR-lntron2-

- GUUUUUUAUUUUUUAUU 17

452 15552

CFTR-lntron2-

- GUGUAAUGGUGCAAUUU 17

453 15553

CFTR-lntron2-

- GGAGGGAAAUAGAUGGGAAA 20

454 15554

CFTR-lntron2-

+ GAAAAAU U U CAUG AACCACA 20

455 15555

CFTR-lntron2-

+ GAGAAAAUAAAACCAGCAUA 20

456 15556

CFTR-lntron2-

- GACUACAGGCAUGCACCACC 20

457 15557

CFTR-lntron2-

- GGGGUUUUGCUAUGCUGGCC 20

458 15558

CFTR-lntron2-

- GGAGUUUCGCCAUGUUGGCC 20

459 15559

CFTR-lntron2-

- GCCUCAGCCUCUCGAGUAGC 20

460 15560

CFTR-lntron2-

+ GCUACUCGAGAGGCUGAGGC 20

461 15561

CFTR-lntron2-

- GAGACGGGGUUUUGCUAUGC 20

462 15562

CFTR-lntron2-

+ GCCUGUAGUCCCAGCUACUC 20

463 15563

CFTR-lntron2-

+ GACUUUGUUUUUAAAAGUAG 20

464 15564

442

5535.1 CFTR-lntron2-

- GGCUAAUUUUUGUAGAGACG 20

465 15565

CFTR-lntron2-

+ GAGAUUCGCUUGAACCCAGG 20

466 15566

CFTR-lntron2-

- GAGAAAGGUGGAGAAGCAUG 20

467 15567

CFTR-lntron2-

- GAAAGGUGGAGAAGCAUGUG 20

468 15568

CFTR-lntron2-

+ GGCCCUAUUCUAGGCACUUG 20

469 15569

CFTR-lntron2-

+ GCACCAUUACACUCCAGCCU 20

470 15570

CFTR-lntron2-

+ GCAUUUUGGGAGGCCAAGGU 20

471 15571

CFTR-lntron2-

- GUGUGCAAAUGCCAUGAGGU 20

472 15572

CFTR-lntron2-

- GAUGUGGAGUUUCGCCAUGU 20

473 15573

CFTR-lntron2-

- GCCUUGGCCUCCCAAAGUGU 20

474 15574

CFTR-lntron2-

- GGAGUGUAAUGGUGCAAUUU 20

475 15575

CFTR-lntron2-

+ GCCACUAAUCCCAACACUUU 20

476 15576

Table 37D provides exemplary targeting domains for correcting a mutation (e.g., 3272- 26->G) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within intron 2. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 37D

443

5535.1 479

CFTR-lntron2-

- UUUCCUUUCCAAUCAAA 17

480 15580

CFTR-lntron2-

+ UGUCACUGGCAAUCAAA 17

481 15581

CFTR-lntron2-

+ CUCCAUCAAAGGAGAAA 17

482 15582

CFTR-lntron2-

- CAUGAUGGAAUGUGAAA 17

483 15583

CFTR-lntron2-

- UAGCUUAAGUAAAUAAA 17

484 15584

CFTR-lntron2-

+ CUUUUUUCUCUUCACAA 17

485 15585

CFTR-lntron2-

- CUCUGUGUGUGAGAGAA 17

486 15586

CFTR-lntron2-

+ U G A A AG A A A A A A U AG A A 17

487 15587

CFTR-lntron2-

+ AUGGGAAAGCCAAGGAA 17

488 15588

CFTR-lntron2-

- AUAAAAGGGUGAGUGAA 17

489 15589

CFTR-lntron2-

+ ACAAACAAAAAACAUAA 17

490 15590

CFTR-lntron2-

+ UUUGUAUUCAAAUAUAA 17

491 15591

CFTR-lntron2-

- AG U U CAAAAU AAU AU AA 17

492 15592

CFTR-lntron2-

- CCCAGGCUGGAGUGUAA 17

493 15593

CFTR-lntron2-

+ CUAAAAUCAUGUAUUAA 17

494 15594

CFTR-lntron2-

+ U U U AAAU UG AAU CAACA 17

495 15595

CFTR-lntron2-

+ U AAG AAAAG AAG U AACA 17

496 15596

CFTR-lntron2-

+ AUCAGAUGGGAAAGCCA 17

497 15597

CFTR-lntron2-

+ UAUGAAAUGUGAAGCCA 17

498 15598

CFTR-lntron2-

+ AACACUUUGGGAGGCCA 17

499 15599

CFTR-lntron2-

+ AGCAUUUUGGGAGGCCA 17

500 15600

444

5535.1 CFTR-lntron2-

+ CAUUUCACAUUCCAUCA 17

501 15601

CFTR-lntron2-

+ AGGAGAAAUGGAUCAGA 17

502 15602

CFTR-lntron2-

- UUCUCCUUUGAUGGAGA 17

503 15603

CFTR-lntron2-

- UAUUAGAGACCAUGAGA 17

504 15604

CFTR-lntron2-

- UUUUAAUUGGAUGCUGA 17

505 15605

CFTR-lntron2-

- AUCCAUUUCUCCUUUGA 17

506 15606

CFTR-lntron2-

- UUUUUUUGGCAUUUUGA 17

507 15607

CFTR-lntron2-

- CCCAAGUGCCUAGAAUA 17

508 15608

CFTR-lntron2-

+ AAAAUAAAACCAGCAUA 17

509 15609

CFTR-lntron2-

+ AAAAAUAAUAGAACGUA 17

510 15610

CFTR-lntron2-

- UGAUACAUUUGUAUUUA 17

511 15611

CFTR-lntron2-

+ AU AAG AAAAG AAG U AAC 17

512 15612

CFTR-lntron2-

+ AAUUGGGUUUCUGUCAC 17

513 15613

CFTR-lntron2-

- CUAAUUUUUGUAGAGAC 17

514 15614

CFTR-lntron2-

- UGAGUAGCUGGGACUAC 17

515 15615

CFTR-lntron2-

- CGAGUAGCUGGGUUUAC 17

516 15616

CFTR-lntron2-

- UACAGGCAUGCACCACC 17

517 15617

CFTR-lntron2-

+ AGAUUUGAAGACAAGCC 17

518 15618

CFTR-lntron2-

+ ACCACUACACUCCAGCC 17

519 15619

CFTR-lntron2-

+ ACCAUUACACUCCAGCC 17

520 15620

CFTR-lntron2-

+ AAAUACAAAAAUUAGCC 17

521 15621

CFTR-lntron2- + CUCUACAAAAAUUAGCC 17 15622

445

5535.1 522

CFTR-lntron2-

+ CAAAAAUUAGCCAGGCC 17

523 15623

CFTR-lntron2-

- CCCUUCUGAUCUGGGCC 17

524 15624

CFTR-lntron2-

- AGUACCUGUUACAUGCC 17

525 15625

CFTR-lntron2-

+ AGUAUAUACCAUAUGCC 17

526 15626

CFTR-lntron2-

- CUGCAAACUCUGCCUCC 17

527 15627

CFTR-lntron2-

- AACAUUCUCUGCUCUCC 17

528 15628

CFTR-lntron2-

- CUGCAAACUUCGUCUCC 17

529 15629

CFTR-lntron2-

- UCAGCCUCUCGAGUAGC 17

530 15630

CFTR-lntron2-

- UCAGUCUCCUGAGUAGC 17

531 15631

CFTR-lntron2-

+ CUUUGGGAGGCCAAGGC 17

532 15632

CFTR-lntron2-

- CGCUGUGUCACCCAGGC 17

533 15633

CFTR-lntron2-

- UGCUCUGUUGCCCAGGC 17

534 15634

CFTR-lntron2-

- UGCUAUGCUGGCCAGGC 17

535 15635

CFTR-lntron2-

- CGCCAUGUUGGCCAGGC 17

536 15636

CFTR-lntron2-

+ ACUCGAGAGGCUGAGGC 17

537 15637

CFTR-lntron2-

- UUGGCCUCCCAAAAUGC 17

538 15638

CFTR-lntron2-

- ACGGGGUUUUGCUAUGC 17

539 15639

CFTR-lntron2-

- CUUCUUCCCUUCUGAUC 17

540 15640

CFTR-lntron2-

+ UGUAGUCCCAGCUACUC 17

541 15641

CFTR-lntron2-

+ CCAAAUGUGUAUUUUUC 17

542 15642

CFTR-lntron2-

+ UGGGAAAGCCAAGGAAG 17

543 15643

446

5535.1 CFTR-lntron2-

- UAAAAGGGUGAGUGAAG 17

544 15644

CFTR-lntron2-

- UCAUUAACAGAAAUCAG 17

545 15645

CFTR-lntron2-

+ AAACCCAGCUACUCGAG 17

546 15646

CFTR-lntron2-

+ CACUCAGAGUGGCUGAG 17

547 15647

CFTR-lntron2-

- CUCUCAGCCACUCUGAG 17

548 15648

CFTR-lntron2-

+ UUCAAAGCUGGGCAUAG 17

549 15649

CFTR-lntron2-

+ UUUGUUUUUAAAAGUAG 17

550 15650

CFTR-lntron2-

- CCCAGGCUGGAGUGUAG 17

551 15651

CFTR-lntron2-

- CAAAGUGUUGGGAUUAG 17

552 15652

CFTR-lntron2-

- UAAUUUUUGUAGAGACG 17

553 15653

CFTR-lntron2-

- UGUGUGUGAGAGAAAGG 17

554 15654

CFTR-lntron2-

+ ACUUUGGGAGGCCAAGG 17

555 15655

CFTR-lntron2-

+ AUUUUGGGAGGCCAAGG 17

556 15656

CFTR-lntron2-

- AAAAGGGUGAGUGAAGG 17

557 15657

CFTR-lntron2-

+ AGGCAAAUGCCACCAGG 17

558 15658

CFTR-lntron2-

+ AUUCGCUUGAACCCAGG 17

559 15659

CFTR-lntron2-

+ AAUCCCAACACUUUGGG 17

560 15660

CFTR-lntron2-

+ AAUCCCAGCAUUUUGGG 17

561 15661

CFTR-lntron2-

+ AAAUUGAAUCAACAUGG 17

562 15662

CFTR-lntron2-

+ AAAUUAGCCAGGCCUGG 17

563 15663

CFTR-lntron2-

+ A A AG A A A A A A U AG A A U G 17

564 15664

CFTR-lntron2- - UUGUAUUUUAGUAGAUG 17 15665

447

5535.1 565

CFTR-lntron2-

+ ACCAAG AG U AGG UG AU G 17

566 15666

CFTR-lntron2-

+ CUGAGAGAUUCUUUAUG 17

567 15667

CFTR-lntron2-

- U A C AG A A A AG C A A AC U G 17

568 15668

CFTR-lntron2-

+ AGCUACUCGAGAGGCUG 17

569 15669

CFTR-lntron2-

- AGGUGGAGAAGCAUGUG 17

570 15670

CFTR-lntron2-

+ AAAUUAGCCAGGCAUUG 17

571 15671

CFTR-lntron2-

+ ACAUAAACCAACAAAAU 17

572 15672

CFTR-lntron2-

- UUCUUUUCU U AU AAAAU 17

573 15673

CFTR-lntron2-

+ UUGAAUUGAAGUAAAAU 17

574 15674

CFTR-lntron2-

- AAUAUCUAAGUUUUAAU 17

575 15675

CFTR-lntron2-

+ UUAAAUUGAAUCAACAU 17

576 15676

CFTR-lntron2-

+ UUUCUUUUAAAUACUAU 17

577 15677

CFTR-lntron2-

- CAAAAUGCUGGGAUUAU 17

578 15678

CFTR-lntron2-

- UGUUUUUUAUUUUUUAU 17

579 15679

CFTR-lntron2-

- UUCUAUUAUUGAACACU 17

580 15680

CFTR-lntron2-

- AAGUGAUCUGCCCACCU 17

581 15681

CFTR-lntron2-

+ CCACUACACUCCAGCCU 17

582 15682

CFTR-lntron2-

+ CCAUUACACUCCAGCCU 17

583 15683

CFTR-lntron2-

- AAGUGAUCUGCCCGCCU 17

584 15684

CFTR-lntron2-

- UGCAAACUCUGCCUCCU 17

585 15685

CFTR-lntron2-

- UGCAAACUUCGUCUCCU 17

586 15686

448

5535.1 CFTR-lntron2-

- AAGGAGCCCUUUGUCCU 17

587 15687

CFTR-lntron2-

- CAGCCUCUCGAGUAGCU 17

588 15688

CFTR-lntron2-

- CAGUCUCCUGAGUAGCU 17

589 15689

CFTR-lntron2-

- UGGCCUCCCAAAAUGCU 17

590 15690

CFTR-lntron2-

- UUCUUCCCUUCUGAUCU 17

591 15691

CFTR-lntron2-

+ AUGCCAGGCCCUAUUCU 17

592 15692

CFTR-lntron2-

- AGCUUUCUACAUAAAGU 17

593 15693

CFTR-lntron2-

+ UUUUGGGAGGCCAAGGU 17

594 15694

CFTR-lntron2-

+ UGAGGAGAAGGCAAGGU 17

595 15695

CFTR-lntron2-

- UGCAAAUGCCAUGAGGU 17

596 15696

CFTR-lntron2-

- UUGGCCUCCCAAAGUGU 17

597 15697

CFTR-lntron2-

- CCUGAAAAAUACACAUU 17

598 15698

CFTR-lntron2-

+ CACUAAUCCCAACACUU 17

599 15699

CFTR-lntron2-

+ CCCUAUUCUAGGCACUU 17

600 15700

CFTR-lntron2-

+ ACUCAAUGUUUUUACUU 17

601 15701

CFTR-lntron2-

- UGGCCUCCCAAAGUGUU 17

602 15702

CFTR-lntron2-

+ CUAUAAUCCCAGCAUUU 17

603 15703

CFTR-lntron2-

- AAUUUAUUGAAAUAUUU 17

604 15704

CFTR-lntron2-

+ ACUAAUCCCAACACUUU 17

605 15705

CFTR-lntron2-

+ UAUAAUCCCAGCAUUUU 17

606 15706

CFTR-lntron2-

+ CUGGGCAAUGUAGUUUU 17

607 15707

CFTR-lntron2- - AAUUCAUUUCCUUUUUU 17 15708

449

5535.1 608

CFTR-lntron2-

- UUCCUUUGUGAAGAGAAAAA 20

609 15709

CFTR-lntron2-

+ CACAUUUAGCCAAGGACAAA 20

610 15710

CFTR-lntron2-

- CAGUUUCCUUUCCAAUCAAA 20

611 15711

CFTR-lntron2-

+ UUCUGUCACUGGCAAUCAAA 20

612 15712

CFTR-lntron2-

- U ACU AG CU UAAG U AAAU AAA 20

613 15713

CFTR-lntron2-

+ CUAUGAAAGAAAAAAUAGAA 20

614 15714

CFTR-lntron2-

+ CAGAUGGGAAAGCCAAGGAA 20

615 15715

CFTR-lntron2-

+ CAAACAAACAAAAAACAUAA 20

616 15716

CFTR-lntron2-

+ ACAUUUGUAUUCAAAUAUAA 20

617 15717

CFTR-lntron2-

- ACAAG U U CAAAAU AAU AU AA 20

618 15718

CFTR-lntron2-

- UUGCCCAGGCUGGAGUGUAA 20

619 15719

CFTR-lntron2-

+ CAAGACCAGCCUGGCCAACA 20

620 15720

CFTR-lntron2-

+ U U U U U U AAAU UG AAU CAACA 20

621 15721

CFTR-lntron2-

+ UUAUAAGAAAAGAAGUAACA 20

622 15722

CFTR-lntron2-

+ UGGAUCAGAUGGGAAAGCCA 20

623 15723

CFTR-lntron2-

+ CCCAACACUUUGGGAGGCCA 20

624 15724

CFTR-lntron2-

+ CCCAGCAUUUUGGGAGGCCA 20

625 15725

CFTR-lntron2-

- CUGGCUAAUUUUUGUAGAGA 20

626 15726

CFTR-lntron2-

- CAUUUCUCCUUUGAUGGAGA 20

627 15727

CFTR-lntron2-

- UUUGUUGAAUGAAUCCAUGA 20

628 15728

CFTR-lntron2-

- CUAGAAUAGGGCCUGGCAUA 20

629 15729

450

5535.1 CFTR-l ntron2-

+ AACAAAAAUAAUAGAACGUA 20

630 15730

CFTR-l ntron2-

- AUGUGAUACAUUUGUAUUUA 20

631 15731

CFTR-l ntron2-

+ U U U AU AAG AAAAG AAG U AAC 20

632 15732

CFTR-l ntron2-

- UGGCUAAUUUUUGUAGAGAC 20

633 15733

CFTR-l ntron2-

- UCCUGAGUAGCUGGGACUAC 20

634 15734

CFTR-l ntron2-

- UCUCGAGUAGCUGGGU UUAC 20

635 15735

CFTR-l ntron2-

+ CAGGAGAAUCACUUGAACCC 20

636 15736

CFTR-l ntron2-

+ ACUGAGAUUCGCUUGAACCC 20

637 15737

CFTR-l ntron2-

- AGAGUCUCGCUGUGUCACCC 20

638 15738

CFTR-l ntron2-

- AGUGGCGUGAGCCACUGCCC 20

639 15739

CFTR-l ntron2-

- AGAGUCUUGCUCUGUUGCCC 20

640 15740

CFTR-l ntron2-

+ CUGAGAUUUGAAGACAAGCC 20

641 15741

CFTR-l ntron2-

+ UCAGGAGUUCAAGACCAGCC 20

642 15742

CFTR-l ntron2-

+ CACACCACUACACUCCAGCC 20

643 15743

CFTR-l ntron2-

+ UGCACCAUUACACUCCAGCC 20

644 15744

CFTR-l ntron2-

+ C U A A A A U AC A A A A A U U AG C C 20

645 15745

CFTR-l ntron2-

+ CGUCUCUACAAAAAUUAGCC 20

646 15746

CFTR-l ntron2-

- CAGGCAUGCACCACCAGGCC 20

647 15747

CFTR-l ntron2-

+ CUACAAAAAUUAGCCAGGCC 20

648 15748

CFTR-l ntron2-

+ CUCUAAAGGAGUAAUAGGCC 20

649 15749

CFTR-l ntron2-

- CAAGUGCCUAGAAUAGGGCC 20

650 15750

CFTR-l ntron2- - CAGGCACUCGCCACAAUGCC 20 15751

451

5535.1 651

CFTR-lntron2-

- UUGAGUACCUGUUACAUGCC 20

652 15752

CFTR-lntron2-

+ UUGAGUAUAUACCAUAUGCC 20

653 15753

CFTR-lntron2-

- UCACUGCAAACUCUGCCUCC 20

654 15754

CFTR-lntron2-

- UCACUGCAAACUUCGUCUCC 20

655 15755

CFTR-lntron2-

- AUCUCAGUCUCCUGAGUAGC 20

656 15756

CFTR-lntron2-

+ ACACUUUGGGAGGCCAAGGC 20

657 15757

CFTR-lntron2-

- UCUCGCUGUGUCACCCAGGC 20

658 15758

CFTR-lntron2-

- UCUUGCUCUGUUGCCCAGGC 20

659 15759

CFTR-lntron2-

- UUUUGCUAUGCUGGCCAGGC 20

660 15760

CFTR-lntron2-

- UUUCGCCAUGUUGGCCAGGC 20

661 15761

CFTR-lntron2-

+ ACUCUAAAGGAGUAAUAGGC 20

662 15762

CFTR-lntron2-

- ACCUUGGCCUCCCAAAAUGC 20

663 15763

CFTR-lntron2-

- UGGUGGCAUUUGCCUUAUGC 20

664 15764

CFTR-lntron2-

+ UCACCCUUUUAUCUGGCAUC 20

665 15765

CFTR-lntron2-

+ CCUUCACUCACCCUUUUAUC 20

666 15766

CFTR-lntron2-

+ CGGGCAGAUCACUUGAGGUC 20

667 15767

CFTR-lntron2-

+ UGGGCAGAUCACUUGAGGUC 20

668 15768

CFTR-lntron2-

+ CAUGGUGGAAACCAUACUUC 20

669 15769

CFTR-lntron2-

+ AAACCAAAUGUGUAUUUUUC 20

670 15770

CFTR-lntron2-

+ AGAUGGGAAAGCCAAGGAAG 20

671 15771

CFTR-lntron2-

- AGAUAAAAGGGUGAGUGAAG 20

672 15772

452

5535.1 CFTR-lntron2-

+ UGUAAACCCAGCUACUCGAG 20

673 15773

CFTR-lntron2-

+ AUAUUCAAAGCUGGGCAUAG 20

674 15774

CFTR-lntron2-

- UCACCCAGGCUGGAGUGUAG 20

675 15775

CFTR-lntron2-

- UCCCAAAGUGUUGGGAUUAG 20

676 15776

CFTR-lntron2-

+ ACAAAGGGCUCCUUCUUUCG 20

677 15777

CFTR-lntron2-

- CUCUGUGUGUGAGAGAAAGG 20

678 15778

CFTR-lntron2-

+ AACACUUUGGGAGGCCAAGG 20

679 15779

CFTR-lntron2-

+ AGCAUUUUGGGAGGCCAAGG 20

680 15780

CFTR-lntron2-

+ UAAGAAAAGAAGUAACAGGG 20

681 15781

CFTR-lntron2-

- AGGUGGAGAAGCAUGUGGGG 20

682 15782

CFTR-lntron2-

+ ACUAAUCCCAACACUUUGGG 20

683 15783

CFTR-lntron2-

+ UAUAAUCCCAGCAUUUUGGG 20

684 15784

CFTR-lntron2-

+ CAAAAAUUAGCCAGGCCUGG 20

685 15785

CFTR-lntron2-

+ AUGAAAGAAAAAAUAGAAUG 20

686 15786

CFTR-lntron2-

- UGGUGUGUGCAAAUGCCAUG 20

687 15787

CFTR-lntron2-

- UUUUUGUAUUUUAGUAGAUG 20

688 15788

CFTR-lntron2-

- U U U U AC AG AAAAG CAAAC U G 20

689 15789

CFTR-lntron2-

+ CCCAGCUACUCGAGAGGCUG 20

690 15790

CFTR-lntron2-

+ C A A A A A UUAGCCAGGCAUUG 20

691 15791

CFTR-lntron2-

+ CAAGGCGGGCAGAUCACUUG 20

692 15792

CFTR-lntron2-

+ CAAGGUGGGCAGAUCACUUG 20

693 15793

CFTR-lntron2- - UACUUCUUUUCUUAUAAAAU 20 15794

453

5535.1 694

CFTR-lntron2-

+ UUGUUGAAUUGAAGUAAAAU 20

695 15795

CFTR-lntron2-

+ UAUGAAAGAAAAAAUAGAAU 20

696 15796

CFTR-lntron2-

- UAUCCCCAAGUGCCUAGAAU 20

697 15797

CFTR-lntron2-

- UUGAAUAUCUAAGUUUUAAU 20

698 15798

CFTR-lntron2-

+ U U U U U AAAU UG AAU CAACAU 20

699 15799

CFTR-lntron2-

+ UGUUUUCUUUUAAAUACUAU 20

700 15800

CFTR-lntron2-

- UCCCAAAAUGCUGGGAUUAU 20

701 15801

CFTR-lntron2-

- UUUUGUUUUUUAUUUUUUAU 20

702 15802

CFTR-lntron2-

+ CAGGCCCUAUUCUAGGCACU 20

703 15803

CFTR-lntron2-

- CUCAAGUGAUCUGCCCACCU 20

704 15804

CFTR-lntron2-

- ACUUUGUACCUCUGCACCCU 20

705 15805

CFTR-lntron2-

+ ACACCACUACACUCCAGCCU 20

706 15806

CFTR-lntron2-

- CUCAAGUGAUCUGCCCGCCU 20

707 15807

CFTR-lntron2-

- CACUGCAAACUCUGCCUCCU 20

708 15808

CFTR-lntron2-

- CACUGCAAACUUCGUCUCCU 20

709 15809

CFTR-lntron2-

- CCUCAGCCUCUCGAGUAGCU 20

710 15810

CFTR-lntron2-

- UCUCAGUCUCCUGAGUAGCU 20

711 15811

CFTR-lntron2-

- CCUUGGCCUCCCAAAAUGCU 20

712 15812

CFTR-lntron2-

+ CAUAUGCCAGGCCCUAUUCU 20

713 15813

CFTR-lntron2-

+ UUUACUUAAGCUAGUAAAUU 20

714 15814

CFTR-lntron2-

- U U U CCUG AAAAAU ACACAU U 20

715 15815

454

5535.1 CFTR-lntron2-

- UUUGUUUUUUAUUUUUUAUU 20

716 15816

CFTR-lntron2-

+ CGCCACUAAUCCCAACACUU 20

717 15817

CFTR-lntron2-

+ AGGCCCUAUUCUAGGCACUU 20

718 15818

CFTR-lntron2-

- CCUUGGCCUCCCAAAGUGUU 20

719 15819

CFTR-lntron2-

+ CACCUAUAAUCCCAGCAUUU 20

720 15820

CFTR-lntron2-

- UGAAAUUUAUUGAAAUAUUU 20

721 15821

CFTR-lntron2-

+ ACCUAUAAUCCCAGCAUUUU 20

722 15822

CFTR-lntron2-

- UUAAAUUCAUUUCCUUUUUU 20

723 15823

Table 38A provides exemplary targeting domains for correcting a mutation (e.g., 3272- 26->G) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within intron 2, have a high level of orthogonality, start with a 5'G, and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 38A

455

5535.1 729

CFTR-lntron2-

+ GCCUUUUUUCUCUUCACAA 19

730 15830

CFTR-lntron2-

+ GAAAGCCUUUUUUCUCUUCACAA 23

731 15831

CFTR-lntron2-

+ GGCUCUAAAUCACUCUAA 18

732 15832

CFTR-lntron2-

+ GCAUUUGAGUCCUUGGUCCCA 21

733 15833

CFTR-lntron2-

+ GGCAUUUGAGUCCUUGGUCCCA 22

734 15834

CFTR-lntron2-

+ GUGGCAUUUGAGUCCUUGGUCCCA 24

735 15835

CFTR-lntron2-

+ GCCAUUACCUUAAGACUUCCCA 22

736 15836

CFTR-lntron2-

+ GUAGAGAGACCAGGAGAGCA 20

737 15837

CFTR-lntron2-

+ GUCCUUAAAGAUAGGAGCA 19

738 15838

CFTR-lntron2-

+ GGUCCUUAAAGAUAGGAGCA 20

739 15839

CFTR-lntron2-

+ GUGGUCCUUAAAGAUAGGAGCA 22

740 15840

CFTR-lntron2-

+ GAACUUGUCAAUAUACCUGCA 21

741 15841

CFTR-lntron2-

+ GCACACUGCAGUUAUGUA 18

742 15842

CFTR-lntron2-

+ GUUUGCACACUGCAGUUAUGUA 22

743 15843

CFTR-lntron2-

+ GGUUUGCACACUGCAGUUAUGUA 23

744 15844

CFTR-lntron2-

+ GGUCGGGGAAUUUCUUUA 18

745 15845

CFTR-lntron2-

+ GCAAGGUCGGGGAAUUUCUUUA 22

746 15846

CFTR-lntron2-

+ GGCAAGGUCGGGGAAUUUCUUUA 23

747 15847

CFTR-lntron2-

+ G CCACAAAU UG U U AG CACC 19

748 15848

CFTR-lntron2-

+ GUGCCACAAAUUGUUAGCACC 21

749 15849

CFTR-lntron2-

+ GGUGCCACAAAUUGUUAGCACC 22

750 15850

456

5535.1 CFTR-lntron2-

+ GAAGCCAGGGUCACUUCCC 19

751 15851

CFTR-lntron2-

+ GUGAAGCCAGGGUCACUUCCC 21

752 15852

CFTR-lntron2-

+ GCAGUUAUGAAAUGUGAAGC 20

753 15853

CFTR-lntron2-

+ GGCAGUUAUGAAAUGUGAAGC 21

754 15854

CFTR-lntron2-

+ GCCUGGCAAUCUCUAAGC 18

755 15855

CFTR-lntron2-

+ GACAAGCCUGGCAAUCUCUAAGC 23

756 15856

CFTR-lntron2-

+ GGCAAUACAGACCUCAGC 18

757 15857

CFTR-lntron2-

+ GCAAGGCAAUACAGACCUCAGC 22

758 15858

CFTR-lntron2-

+ GAGCAAGGCAAUACAGACCUCAGC 24

759 15859

CFTR-lntron2-

+ GCCAUUUCACAUUCCAUC 18

760 15860

CFTR-lntron2-

+ GCUAGCCAUUUCACAUUCCAUC 22

761 15861

CFTR-lntron2-

+ GGGUAAGCACUAUGACUC 18

762 15862

CFTR-lntron2-

+ GGGGUAAGCACUAUGACUC 19

763 15863

CFTR-lntron2-

+ GCACUAUGACUCAAGAGUCUC 21

764 15864

CFTR-lntron2-

+ GAGGAGAAGGCAAGGUCG 18

765 15865

CFTR-lntron2-

+ GUUUGUACUGGCAUAGCAUUG 21

766 15866

CFTR-lntron2-

+ GGUUUGUACUGGCAUAGCAUUG 22

767 15867

CFTR-lntron2-

+ GGGUUUGUACUGGCAUAGCAUUG 23

768 15868

CFTR-lntron2-

+ GCAAAUGCCACCAGGUGGCAU 21

769 15869

CFTR-lntron2-

+ GGCAAAUGCCACCAGGUGGCAU 22

770 15870

CFTR-lntron2-

+ GAUAAUGAUGCUUUCCACU 19

771 15871

CFTR-lntron2- + GCCUAGUUCAUUCUAGACU 19 15872

457

5535.1 772

CFTR-lntron2-

+ GCUACUCCCACUAGCUUAAUUCU 23

773 15873

CFTR-lntron2-

+ GCCCUUGAUCUUAGAAGU 18

774 15874

CFTR-lntron2-

+ GGCCCUUGAUCUUAGAAGU 19

775 15875

CFTR-lntron2-

+ GCUGGCCCUUGAUCUUAGAAGU 22

776 15876

CFTR-lntron2-

- GACCAGCUUUCUACAUAAA 19

777 15877

CFTR-lntron2-

- GGACCAGCUUUCUACAUAAA 20

778 15878

CFTR-lntron2-

- GACCGGACCAGCUUUCUACAUAAA 24

779 15879

CFTR-lntron2-

- GCACAGGCCUGAUGCCAGAUAA 22

780 15880

CFTR-lntron2-

- GCUUUGAAUAUCUAAGUUUUAA 22

781 15881

CFTR-lntron2-

- G AAAAAU ACACAU UUGGUUUCA 22

782 15882

CFTR-lntron2-

- G C U U A AG U AAA U A A A AG G A 19

783 15883

CFTR-lntron2-

- GCUCAAUUUUGUGACCAUGGA 21

784 15884

CFTR-lntron2-

- GGCUCAAUUUUGUGACCAUGGA 22

785 15885

CFTR-lntron2-

- GUUUUAAUUGGAUGCUGA 18

786 15886

CFTR-lntron2-

- GAAUGGUAGUCCCCCCCAUA 20

787 15887

CFTR-lntron2-

- GGAAUGGUAGUCCCCCCCAUA 21

788 15888

CFTR-lntron2-

- GACAAGUUCAAAAUAAUAUA 20

789 15889

CFTR-lntron2-

- GCUCUCAUUAGCAAGCUUCUA 21

790 15890

CFTR-lntron2-

- GGCUCUCAUUAGCAAGCUUCUA 22

791 15891

CFTR-lntron2-

- GGGCUCUCAUUAGCAAGCUUCUA 23

792 15892

CFTR-lntron2-

- GUUCAAAAUAAUAUAAUGGGUA 22

793 15893

458

5535.1 CFTR-lntron2-

- GAUAAUAUACUUUGCCAGUUA 21

794 15894

CFTR-lntron2-

- GAGAUAAUAUACUUUGCCAGUUA 23

795 15895

CFTR-lntron2-

- GUAUUUAUGGCCAGAUAGAGAAC 23

796 15896

CFTR-lntron2-

- GAUGUAUCCCCAAGUGCC 18

797 15897

CFTR-lntron2-

- GUUCCUAAAACUACAUUGCC 20

798 15898

CFTR-lntron2-

- GAAAAAUCCCAGAGACUC 18

799 15899

CFTR-lntron2-

- GUGAAAAAUCCCAGAGACUC 20

800 15900

CFTR-lntron2-

- GCCAGAUAAAAGGGUGAGUGAAG 23

801 15901

CFTR-lntron2-

- GUCUUAUUAGAGACCAUGAG 20

802 15902

CFTR-lntron2-

- GCCUGAUGCCAGAUAAAAGG 20

803 15903

CFTR-lntron2-

- GUACCUGUUACAUGCCAGG 19

804 15904

CFTR-lntron2-

- GAGUACCUGUUACAUGCCAGG 21

805 15905

CFTR-lntron2-

- GAAUGAUUAAUCAGAGUAGGG 21

806 15906

CFTR-lntron2-

- GGAAUGAUUAAUCAGAGUAGGG 22

807 15907

CFTR-lntron2-

- GGGAAUGAUUAAUCAGAGUAGGG 23

808 15908

CFTR-lntron2-

- GAACAUGAAUCUGAAUUUG 19

809 15909

CFTR-lntron2-

- GCCAGAUAGAGAACAUGAAU 20

810 15910

CFTR-lntron2-

- GAUGCUGAGGGAAUGAUUAAU 21

811 15911

CFTR-lntron2-

- GGAUGCUGAGGGAAUGAUUAAU 22

812 15912

CFTR-lntron2-

- GCUUUCAAAACCUUUAUAU 19

813 15913

CFTR-lntron2-

- GAAUAUCUCCUCUCAGCCACU 21

814 15914

CFTR-lntron2- - GUAGAAUAUCUCCUCUCAGCCACU 24 15915

459

5535.1 815

CFTR-lntron2-

- GCUCCAUAUUUAGCUUCUUACU 22

816 15916

CFTR-lntron2-

- GUCUGUAUUGCCUUGCUCUCU 21

817 15917

CFTR-lntron2-

- GGUCUGUAUUGCCUUGCUCUCU 22

818 15918

CFTR-lntron2-

- GAGGUCUGUAUUGCCUUGCUCUCU 24

819 15919

CFTR-lntron2-

- GUUUCCUUUCCAAUCAAAAGGU 22

820 15920

CFTR-lntron2-

- GCCCCGGCCUAUUACUCCUU 20

821 15921

CFTR-lntron2-

- GUCAGGAUAUGAACUUUUU 19

822 15922

CFTR-lntron2-

- GUAGUCAGGAUAUGAACUUUUU 22

823 15923

Table 38B provides exemplary targeting domains for correcting a mutation (e.g., 3272- 26->G) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within intron 2, have a high level of orthogonality and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 38B

460

5535.1 CFTR-lntron2-

+ UUUAUUUACUUAAGCUAGUAAA 22

829 15929

CFTR-lntron2-

+ UUUUAUUUACUUAAGCUAGUAAA 23

830 15930

CFTR-lntron2-

+ CUUUUAUUUACUUAAGCUAGUAAA 24

831 15931

CFTR-lntron2-

+ CCUUUUUUCUCUUCACAA 18

832 15932

CFTR-lntron2-

+ AGCCUUUUUUCUCUUCACAA 20

233 15333

CFTR-lntron2-

+ AAGCCUUUUUUCUCUUCACAA 21

833 15933

CFTR-lntron2-

+ AAAGCCUUUUUUCUCUUCACAA 22

834 15934

CFTR-lntron2-

+ UGAAAGCCUUUUUUCUCUUCACAA 24

835 15935

CFTR-lntron2-

+ ACCUUCUCCAUCAAAGGAGAA 21

836 15936

CFTR-lntron2-

+ CACCUUCUCCAUCAAAGGAGAA 22

837 15937

CFTR-lntron2-

+ U CACCU U CU CCAU CAAAGG AG AA 23

838 15938

CFTR-lntron2-

+ CUCACCUUCUCCAUCAAAGGAGAA 24

839 15939

CFTR-lntron2-

+ UGGCUCUAAAUCACUCUAA 19

840 15940

CFTR-lntron2-

+ AUGGCUCUAAAUCACUCUAA 20

250 15350

CFTR-lntron2-

+ CAUGGCUCUAAAUCACUCUAA 21

841 15941

CFTR-lntron2-

+ ACAUGGCUCUAAAUCACUCUAA 22

842 15942

CFTR-lntron2-

+ AACAUGGCUCUAAAUCACUCUAA 23

843 15943

CFTR-lntron2-

+ AAACAUGGCUCUAAAUCACUCUAA 24

844 15944

CFTR-lntron2-

+ UAGACUAUGAGUGGCCCA 18

845 15945

CFTR-lntron2-

+ CUAGACUAUGAGUGGCCCA 19

846 15946

CFTR-lntron2-

+ UCUAGACUAUGAGUGGCCCA 20

261 15361

CFTR-lntron2- + UUCUAGACUAUGAGUGGCCCA 21 15947

461

5535.1 847

CFTR-lntron2-

+ AUUCUAGACUAUGAGUGGCCCA 22

848 15948

CFTR-lntron2-

+ CAUUCUAGACUAUGAGUGGCCCA 23

849 15949

CFTR-lntron2-

+ UCAUUCUAGACUAUGAGUGGCCCA 24

850 15950

CFTR-lntron2-

+ UUUGAGUCCUUGGUCCCA 18

851 15951

CFTR-lntron2-

+ AUUUGAGUCCUUGGUCCCA 19

852 15952

CFTR-lntron2-

+ CAUUUGAGUCCUUGGUCCCA 20

853 15953

CFTR-lntron2-

+ UGGCAUUUGAGUCCUUGGUCCCA 23

854 15954

CFTR-lntron2-

+ UUACCUUAAGACUUCCCA 18

855 15955

CFTR-lntron2-

+ AUUACCUUAAGACUUCCCA 19

856 15956

CFTR-lntron2-

+ CAUUACCUUAAGACUUCCCA 20

263 15363

CFTR-lntron2-

+ CCAUUACCUUAAGACUUCCCA 21

857 15957

CFTR-lntron2-

+ AGCCAUUACCUUAAGACUUCCCA 23

858 15958

CFTR-lntron2-

+ UAGCCAUUACCUUAAGACUUCCCA 24

859 15959

CFTR-lntron2-

+ AGAGAGACCAGGAGAGCA 18

860 15960

CFTR-lntron2-

+ UAGAGAGACCAGGAGAGCA 19

861 15961

CFTR-lntron2-

+ UCCUUAAAGAUAGGAGCA 18

862 15962

CFTR-lntron2-

+ UGGUCCUUAAAGAUAGGAGCA 21

863 15963

CFTR-lntron2-

+ CGUGGUCCUUAAAGAUAGGAGCA 23

864 15964

CFTR-lntron2-

+ UCGUGGUCCUUAAAGAUAGGAGCA 24

865 15965

CFTR-lntron2-

+ CUUGUCAAUAUACCUGCA 18

866 15966

CFTR-lntron2-

+ ACUUGUCAAUAUACCUGCA 19

867 15967

462

5535.1 CFTR-lntron2-

+ AACUUGUCAAUAUACCUGCA 20

868 15968

CFTR-lntron2-

+ UGAACUUGUCAAUAUACCUGCA 22

869 15969

CFTR-lntron2-

+ UUGAACUUGUCAAUAUACCUGCA 23

870 15970

CFTR-lntron2-

+ UUUGAACUUGUCAAUAUACCUGCA 24

871 15971

CFTR-lntron2-

+ AGAUGGGAAAGCCAAGGA 18

872 15972

CFTR-lntron2-

+ CAGAUGGGAAAGCCAAGGA 19

873 15973

CFTR-lntron2-

+ UCAGAUGGGAAAGCCAAGGA 20

280 15380

CFTR-lntron2-

+ CCUGACUACAAUCUUGGA 18

874 15974

CFTR-lntron2-

+ UCCUGACUACAAUCUUGGA 19

875 15975

CFTR-lntron2-

+ AUCCUGACUACAAUCUUGGA 20

876 15976

CFTR-lntron2-

+ UAUCCUGACUACAAUCUUGGA 21

877 15977

CFTR-lntron2-

+ AUAUCCUGACUACAAUCUUGGA 22

878 15978

CFTR-lntron2-

+ CAUAUCCUGACUACAAUCUUGGA 23

879 15979

CFTR-lntron2-

+ UCAUAUCCUGACUACAAUCUUGGA 24

880 15980

CFTR-lntron2-

+ UGCACACUGCAGUUAUGUA 19

881 15981

CFTR-lntron2-

+ UUGCACACUGCAGUUAUGUA 20

882 15982

CFTR-lntron2-

+ UUUGCACACUGCAGUUAUGUA 21

883 15983

CFTR-lntron2-

+ UGGUUUGCACACUGCAGUUAUGUA 24

884 15984

CFTR-lntron2-

+ AGGUCGGGGAAUUUCUUUA 19

885 15985

CFTR-lntron2-

+ AAGGUCGGGGAAUUUCUUUA 20

886 15986

CFTR-lntron2-

+ CAAGGUCGGGGAAUUUCUUUA 21

887 15987

463

5535.1 CFTR-lntron2-

+ AGGCAAGGUCGGGGAAUUUCUUUA 24

888 15988

CFTR-lntron2-

+ CCACAAAUUGUUAGCACC 18

889 15989

CFTR-lntron2-

+ UGCCACAAAUUGUUAGCACC 20

890 15990

CFTR-lntron2-

+ UGGUGCCACAAAUUGUUAGCACC 23

891 15991

CFTR-lntron2-

+ UUGGUGCCACAAAUUGUUAGCACC 24

892 15992

CFTR-lntron2-

+ AAGCCAGGGUCACUUCCC 18

893 15993

CFTR-lntron2-

+ UGAAGCCAGGGUCACUUCCC 20

894 15994

CFTR-lntron2-

+ UGUGAAGCCAGGGUCACUUCCC 22

895 15995

CFTR-lntron2-

+ AUGUGAAGCCAGGGUCACUUCCC 23

896 15996

CFTR-lntron2-

+ AAUGUGAAGCCAGGGUCACUUCCC 24

897 15997

CFTR-lntron2-

+ AGUUAUGAAAUGUGAAGC 18

898 15998

CFTR-lntron2-

+ CAGUUAUGAAAUGUGAAGC 19

899 15999

CFTR-lntron2-

+ AGGCAGUUAUGAAAUGUGAAGC 22

900 16000

CFTR-lntron2-

+ AAGGCAGUUAUGAAAUGUGAAGC 23

901 16001

CFTR-lntron2-

+ CAAGGCAGUUAUGAAAUGUGAAGC 24

902 16002

CFTR-lntron2-

+ AGCCUGGCAAUCUCUAAGC 19

903 16003

CFTR-lntron2-

+ AAGCCUGGCAAUCUCUAAGC 20

904 16004

CFTR-lntron2-

+ CAAGCCUGGCAAUCUCUAAGC 21

905 16005

CFTR-lntron2-

+ ACAAGCCUGGCAAUCUCUAAGC 22

906 16006

CFTR-lntron2-

+ AGACAAGCCUGGCAAUCUCUAAGC 24

907 16007

CFTR-lntron2-

+ AGGCAAUACAGACCUCAGC 19

908 16008

CFTR-lntron2- + AAGGCAAUACAGACCUCAGC 20 15422

464

5535.1 322

CFTR-lntron2-

+ CAAGGCAAUACAGACCUCAGC 21

909 16009

CFTR-lntron2-

+ AGCAAGGCAAUACAGACCUCAGC 23

910 16010

CFTR-lntron2-

+ AGCCAUUUCACAUUCCAUC 19

911 16011

CFTR-lntron2-

+ UAGCCAUUUCACAUUCCAUC 20

912 16012

CFTR-lntron2-

+ CUAGCCAUUUCACAUUCCAUC 21

913 16013

CFTR-lntron2-

+ UGCUAGCCAUUUCACAUUCCAUC 23

914 16014

CFTR-lntron2-

+ AUGCUAGCCAUUUCACAUUCCAUC 24

915 16015

CFTR-lntron2-

+ AGGGGUAAGCACUAUGACUC 20

916 16016

CFTR-lntron2-

+ AAGGGGUAAGCACUAUGACUC 21

917 16017

CFTR-lntron2-

+ CAAGGGGUAAGCACUAUGACUC 22

918 16018

CFTR-lntron2-

+ CCAAGGGGUAAGCACUAUGACUC 23

919 16019

CFTR-lntron2-

+ CCCAAGGGGUAAGCACUAUGACUC 24

920 16020

CFTR-lntron2-

+ CUAUGACUCAAGAGUCUC 18

921 16021

CFTR-lntron2-

+ ACUAUGACUCAAGAGUCUC 19

922 16022

CFTR-lntron2-

+ CACUAUGACUCAAGAGUCUC 20

331 15431

CFTR-lntron2-

+ AGCACUAUGACUCAAGAGUCUC 22

923 16023

CFTR-lntron2-

+ AAGCACUAUGACUCAAGAGUCUC 23

924 16024

CFTR-lntron2-

+ UAAGCACUAUGACUCAAGAGUCUC 24

925 16025

CFTR-lntron2-

+ UGAGGAGAAGGCAAGGUCG 19

926 16026

CFTR-lntron2-

+ CUGAGGAGAAGGCAAGGUCG 20

349 15449

CFTR-lntron2-

+ UUAAAUUGAAUCAACAUG 18

927 16027

465

5535.1 CFTR-lntron2-

+ UUUAAAUUGAAUCAACAUG 19

928 16028

CFTR-lntron2-

+ UUUUAAAUUGAAUCAACAUG 20

358 15458

CFTR-lntron2-

+ UGUACUGGCAUAGCAUUG 18

929 16029

CFTR-lntron2-

+ UUGUACUGGCAUAGCAUUG 19

930 16030

CFTR-lntron2-

+ UUUGUACUGGCAUAGCAUUG 20

931 16031

CFTR-lntron2-

+ UGGGUUUGUACUGGCAUAGCAUUG 24

932 16032

CFTR-lntron2-

+ AGGCAAAUGCCACCAGGUGGCAU 23

933 16033

CFTR-lntron2-

+ AAGGCAAAUGCCACCAGGUGGCAU 24

934 16034

CFTR-lntron2-

+ AUAAUGAUGCUUUCCACU 18

935 16035

CFTR-lntron2-

+ AGAUAAUGAUGCUUUCCACU 20

936 16036

CFTR-lntron2-

+ CCUAGUUCAUUCUAGACU 18

937 16037

CFTR-lntron2-

+ AGCCUAGUUCAUUCUAGACU 20

938 16038

CFTR-lntron2-

+ CAGCCUAGUUCAUUCUAGACU 21

939 16039

CFTR-lntron2-

+ UCAGCCUAGUUCAUUCUAGACU 22

940 16040

CFTR-lntron2-

+ CUCAGCCUAGUUCAUUCUAGACU 23

941 16041

CFTR-lntron2-

+ ACUCAGCCUAGUUCAUUCUAGACU 24

942 16042

CFTR-lntron2-

+ CCAUAACAUUUGGUUACU 18

943 16043

CFTR-lntron2-

+ UCCAUAACAUUUGGUUACU 19

944 16044

CFTR-lntron2-

+ AUCCAUAACAUUUGGUUACU 20

945 16045

CFTR-lntron2-

+ CAUCCAUAACAUUUGGUUACU 21

946 16046

CFTR-lntron2-

+ CCAUCCAUAACAUUUGGUUACU 22

947 16047

CFTR-lntron2- + CCCAUCCAUAACAUUUGGUUACU 23 16048

466

5535.1 948

CFTR-lntron2-

+ UCCCAUCCAUAACAUUUGGUUACU 24

949 16049

CFTR-lntron2-

+ UCCCACUAGCUUAAUUCU 18

950 16050

CFTR-lntron2-

+ CUCCCACUAGCUUAAUUCU 19

951 16051

CFTR-lntron2-

+ ACUCCCACUAGCUUAAUUCU 20

952 16052

CFTR-lntron2-

+ UACUCCCACUAGCUUAAUUCU 21

953 16053

CFTR-lntron2-

+ CUACUCCCACUAGCUUAAUUCU 22

954 16054

CFTR-lntron2-

+ UGCUACUCCCACUAGCUUAAUUCU 24

955 16055

CFTR-lntron2-

+ UGGCCCUUGAUCUUAGAAGU 20

956 16056

CFTR-lntron2-

+ CUGGCCCUUGAUCUUAGAAGU 21

957 16057

CFTR-lntron2-

+ AGCUGGCCCUUGAUCUUAGAAGU 23

958 16058

CFTR-lntron2-

+ AAGCUGGCCCUUGAUCUUAGAAGU 24

959 16059

CFTR-lntron2-

- ACCAGCUUUCUACAUAAA 18

960 16060

CFTR-lntron2-

- CGGACCAGCUUUCUACAUAAA 21

961 16061

CFTR-lntron2-

- CCGGACCAGCUUUCUACAUAAA 22

962 16062

CFTR-lntron2-

- ACCGGACCAGCUUUCUACAUAAA 23

963 16063

CFTR-lntron2-

- AGGCCUGAUGCCAGAUAA 18

964 16064

CFTR-lntron2-

- CAGGCCUGAUGCCAGAUAA 19

965 16065

CFTR-lntron2-

- ACAGGCCUGAUGCCAGAUAA 20

966 16066

CFTR-lntron2-

- CACAGGCCUGAUGCCAGAUAA 21

967 16067

CFTR-lntron2-

- AGCA CAGGCCUGAUGCCAGAUAA 23

968 16068

CFTR-lntron2-

- CAGCACAGGCCUGAUGCCAGAUAA 24

969 16069

467

5535.1 CFTR-lntron2-

- CUUUGAAUAUCUAAGUUUUAA 21

970 16070

CFTR-lntron2-

- AGCUUUGAAUAUCUAAGUUUUAA 23

971 16071

CFTR-lntron2-

- CAG CU U UG AAU AU CU AAG U U U U AA 24

972 16072

CFTR-lntron2-

- UGCACCAAAGUAAAAACA 18

973 16073

CFTR-lntron2-

- U U G C ACCAAAG U AAAAACA 19

974 16074

CFTR-lntron2-

- AU UG CACCAAAG U AAAAACA 20

975 16075

CFTR-lntron2-

- UAU UG CACCAAAG U AAAAACA 21

976 16076

CFTR-lntron2-

- U UAU UG CACCAAAG U AAAAACA 22

977 16077

CFTR-lntron2-

- AUUAUUGCACCAAAGUAAAAACA 23

978 16078

CFTR-lntron2-

- AAU UAU UG CACCAAAG U AAAAACA 24

979 16079

CFTR-lntron2-

- AAAAAUACACAUUUGGUUUCA 21

980 16080

CFTR-lntron2-

- UGAAAAAUACACAUUUGGUUUCA 23

981 16081

CFTR-lntron2-

- CUG AAAAAU ACACAU UUGGUUUCA 24

982 16082

CFTR-lntron2-

- CU U AAG U AAA U A A A AG G A 18

983 16083

CFTR-lntron2-

- AGCUUAAGUAAAUAAAAGGA 20

984 16084

CFTR-lntron2-

- CAAUUUUGUGACCAUGGA 18

985 16085

CFTR-lntron2-

- UCAAUUUUGUGACCAUGGA 19

986 16086

CFTR-lntron2-

- CUCAAUUUUGUGACCAUGGA 20

987 16087

CFTR-lntron2-

- UGGCUCAAUUUUGUGACCAUGGA 23

988 16088

CFTR-lntron2-

- CUGGCUCAAUUUUGUGACCAUGGA 24

989 16089

CFTR-lntron2-

- AGUUUUAAUUGGAUGCUGA 19

990 16090

CFTR-lntron2- - AAGUUUUAAUUGGAUGCUGA 20 15382

468

5535.1 282

CFTR-lntron2-

- UAAGUUUUAAUUGGAUGCUGA 21

991 16091

CFTR-lntron2-

- CUAAGUUUUAAUUGGAUGCUGA 22

992 16092

CFTR-lntron2-

- UCUAAGUUUUAAUUGGAUGCUGA 23

993 16093

CFTR-lntron2-

- AUCUAAGUUUUAAUUGGAUGCUGA 24

994 16094

CFTR-lntron2-

- AUGGUAGUCCCCCCCAUA 18

995 16095

CFTR-lntron2-

- AAUGGUAGUCCCCCCCAUA 19

996 16096

CFTR-lntron2-

- AGGAAUGGUAGUCCCCCCCAUA 22

997 16097

CFTR-lntron2-

- UAGGAAUGGUAGUCCCCCCCAUA 23

998 16098

CFTR-lntron2-

- CUAGGAAUGGUAGUCCCCCCCAUA 24

999 16099

CFTR-lntron2-

- CAAG UU CAAAAU AAU AU A 18

1000 16100

CFTR-lntron2-

- ACAAG U U CAAAAU AAU AU A 19

1001 16101

CFTR-lntron2-

- UGACAAGUUCAAAAUAAUAUA 21

1002 16102

CFTR-lntron2-

- UUGACAAGUUCAAAAUAAUAUA 22

1003 16103

CFTR-lntron2-

- AU UG ACAAG U U CAAAAU AAU AU A 23

1004 16104

CFTR-lntron2-

- U AU UG ACAAG U U CAAAAU AAU AU A 24

1005 16105

CFTR-lntron2-

- CUCAUUAGCAAGCUUCUA 18

1006 16106

CFTR-lntron2-

- UCUCAUUAGCAAGCUUCUA 19

1007 16107

CFTR-lntron2-

- CUCUCAUUAGCAAGCUUCUA 20

290 15390

CFTR-lntron2-

- AGGGCUCUCAUUAGCAAGCUUCUA 24

1008 16108

CFTR-lntron2-

- AAAAUAAUAUAAUGGGUA 18

1009 16109

CFTR-lntron2-

- CAAAAUAAUAUAAUGGGUA 19

1010 16110

469

5535.1 CFTR-lntron2-

- UCAAAAUAAUAUAAUGGGUA 20

1011 16111

CFTR-lntron2-

- U U CAAAAU AAU AU AAUGGG U A 21

1012 16112

CFTR-lntron2-

- AGUUCAAAAUAAUAUAAUGGGUA 23

1013 16113

CFTR-lntron2-

- AAG U U CAAAAU AAU AU AAUGGG U A 24

1014 16114

CFTR-lntron2-

- AAUAUACUUUGCCAGUUA 18

1015 16115

CFTR-lntron2-

- UAAUAUACUUUGCCAGUUA 19

1016 16116

CFTR-lntron2-

- AUAAUAUACUUUGCCAGUUA 20

1017 16117

CFTR-lntron2-

- AGAUAAUAUACUUUGCCAGUUA 22

1018 16118

CFTR-lntron2-

- AGAGAUAAUAUACUUUGCCAGUUA 24

1019 16119

CFTR-lntron2-

- UAUGGCCAGAUAGAGAAC 18

1020 16120

CFTR-lntron2-

- UUAUGGCCAGAUAGAGAAC 19

1021 16121

CFTR-lntron2-

- UUUAUGGCCAGAUAGAGAAC 20

1022 16122

CFTR-lntron2-

- AUUUAUGGCCAGAUAGAGAAC 21

1023 16123

CFTR-lntron2-

- UAUUUAUGGCCAGAUAGAGAAC 22

1024 16124

CFTR-lntron2-

- UGUAUUUAUGGCCAGAUAGAGAAC 24

1025 16125

CFTR-lntron2-

- UGGCUCAAUUUUGUGACC 18

1026 16126

CFTR-lntron2-

- CUGGCUCAAUUUUGUGACC 19

1027 16127

CFTR-lntron2-

- UCUGGCUCAAUUUUGUGACC 20

1028 16128

CFTR-lntron2-

- AUCUGGCUCAAUUUUGUGACC 21

1029 16129

CFTR-lntron2-

- UAUCUGGCUCAAUUUUGUGACC 22

1030 16130

CFTR-lntron2-

- CUAUCUGGCUCAAUUUUGUGACC 23

1031 16131

470

5535.1 CFTR-lntron2-

- CCUAUCUGGCUCAAUUUUGUGACC 24

1032 16132

CFTR-lntron2-

- UGAUGUAUCCCCAAGUGCC 19

1033 16133

CFTR-lntron2-

- AUGAUGUAUCCCCAAGUGCC 20

1034 16134

CFTR-lntron2-

- UCCUAAAACUACAUUGCC 18

1035 16135

CFTR-lntron2-

- UUCCUAAAACUACAUUGCC 19

1036 16136

CFTR-lntron2-

- UGUUCCUAAAACUACAUUGCC 21

1037 16137

CFTR-lntron2-

- AUGUUCCUAAAACUACAUUGCC 22

1038 16138

CFTR-lntron2-

- CAUGUUCCUAAAACUACAUUGCC 23

1039 16139

CFTR-lntron2-

- CCAUGUUCCUAAAACUACAUUGCC 24

1040 16140

CFTR-lntron2-

- UGAAAAAUCCCAGAGACUC 19

1041 16141

CFTR-lntron2-

- UGUGAAAAAUCCCAGAGACUC 21

1042 16142

CFTR-lntron2-

- AUGUGAAAAAUCCCAGAGACUC 22

1043 16143

CFTR-lntron2-

- AAUGUGAAAAAUCCCAGAGACUC 23

1044 16144

CFTR-lntron2-

- AAAUGUGAAAAAUCCCAGAGACUC 24

1045 16145

CFTR-lntron2-

- CUUGGGCCACUCAUAGUC 18

1046 16146

CFTR-lntron2-

- CCUUGGGCCACUCAUAGUC 19

1047 16147

CFTR-lntron2-

- CCCUUGGGCCACUCAUAGUC 20

1048 16148

CFTR-lntron2-

- CCCCUUGGGCCACUCAUAGUC 21

1049 16149

CFTR-lntron2-

- ACCCCUUGGGCCACUCAUAGUC 22

1050 16150

CFTR-lntron2-

- UACCCCUUGGGCCACUCAUAGUC 23

1051 16151

CFTR-lntron2-

- UUACCCCUUGGGCCACUCAUAGUC 24

1052 16152

471

5535.1 CFTR-lntron2-

- AUUUCUCCUUUGAUGGAGAAG 21

1053 16153

CFTR-lntron2-

- CAUUUCUCCUUUGAUGGAGAAG 22

1054 16154

CFTR-lntron2-

- CCAUUUCUCCUUUGAUGGAGAAG 23

1055 16155

CFTR-lntron2-

- UCCAUUUCUCCUUUGAUGGAGAAG 24

1056 16156

CFTR-lntron2-

- CAGAUAAAAGGGUGAGUGAAG 21

1057 16157

CFTR-lntron2-

- CCAGAUAAAAGGGUGAGUGAAG 22

1058 16158

CFTR-lntron2-

- UGCCAGAUAAAAGGGUGAGUGAAG 24

1059 16159

CFTR-lntron2-

- CUUAUUAGAGACCAUGAG 18

1060 16160

CFTR-lntron2-

- UCUUAUUAGAGACCAUGAG 19

1061 16161

CFTR-lntron2-

- UGUCUUAUUAGAGACCAUGAG 21

1062 16162

CFTR-lntron2-

- UUGUCUUAUUAGAGACCAUGAG 22

1063 16163

CFTR-lntron2-

- UUUGUCUUAUUAGAGACCAUGAG 23

1064 16164

CFTR-lntron2-

- AUUUGUCUUAUUAGAGACCAUGAG 24

1065 16165

CFTR-lntron2-

- CUGAUGCCAGAUAAAAGG 18

1066 16166

CFTR-lntron2-

- CCUGAUGCCAGAUAAAAGG 19

1067 16167

CFTR-lntron2-

- UACCUGUUACAUGCCAGG 18

1068 16168

CFTR-lntron2-

- AGUACCUGUUACAUGCCAGG 20

1069 16169

CFTR-lntron2-

- UGAGUACCUGUUACAUGCCAGG 22

1070 16170

CFTR-lntron2-

- UUGAGUACCUGUUACAUGCCAGG 23

1071 16171

CFTR-lntron2-

- UUUGAGUACCUGUUACAUGCCAGG 24

1072 16172

CFTR-lntron2-

- AGUCUAGAAUGAACUAGG 18

1073 16173

472

5535.1 CFTR-lntron2-

- UAGUCUAGAAUGAACUAGG 19

1074 16174

CFTR-lntron2-

- AUAGUCUAGAAUGAACUAGG 20

1075 16175

CFTR-lntron2-

- CAUAGUCUAGAAUGAACUAGG 21

1076 16176

CFTR-lntron2-

- UCAUAGUCUAGAAUGAACUAGG 22

1077 16177

CFTR-lntron2-

- CUCAUAGUCUAGAAUGAACUAGG 23

1078 16178

CFTR-lntron2-

- ACUCAUAGUCUAGAAUGAACUAGG 24

1079 16179

CFTR-lntron2-

- UGAUUAAUCAGAGUAGGG 18

1080 16180

CFTR-lntron2-

- AUGAUUAAUCAGAGUAGGG 19

1081 16181

CFTR-lntron2-

- AAUGAUUAAUCAGAGUAGGG 20

1082 16182

CFTR-lntron2-

- AGGGAAUGAUUAAUCAGAGUAGGG 24

1083 16183

CFTR-lntron2-

- UUUAUUGAAAUAUUUUGG 18

1084 16184

CFTR-lntron2-

- AUUUAUUGAAAUAUUUUGG 19

1085 16185

CFTR-lntron2-

- AAUUUAUUGAAAUAUUUUGG 20

1086 16186

CFTR-lntron2-

- AACAUGAAUCUGAAUUUG 18

1087 16187

CFTR-lntron2-

- AGAACAUGAAUCUGAAUUUG 20

1088 16188

CFTR-lntron2-

- CAGAUAGAGAACAUGAAU 18

1089 16189

CFTR-lntron2-

- CCAGAUAGAGAACAUGAAU 19

1090 16190

CFTR-lntron2-

- UGGUAACUUGACAGUAAU 18

1091 16191

CFTR-lntron2-

- AUGGUAACUUGACAGUAAU 19

1092 16192

CFTR-lntron2-

- UAUGGUAACUUGACAGUAAU 20

373 15473

CFTR-lntron2-

- UUAUGGUAACUUGACAGUAAU 21

1093 16193

473

5535.1 CFTR-lntron2-

- CUUAUGGUAACUUGACAGUAAU 22

1094 16194

CFTR-lntron2-

- ACUUAUGGUAACUUGACAGUAAU 23

1095 16195

CFTR-lntron2-

- UACUUAUGGUAACUUGACAGUAAU 24

1096 16196

CFTR-lntron2-

- UGGAUGCUGAGGGAAUGAUUAAU 23

1097 16197

CFTR-lntron2-

- UUGGAUGCUGAGGGAAUGAUUAAU 24

1098 16198

CFTR-lntron2-

- CUUUCAAAACCUUUAUAU 18

1099 16199

CFTR-lntron2-

- UGCUUUCAAAACCUUUAUAU 20

1100 16200

CFTR-lntron2-

- UAUCUCCUCUCAGCCACU 18

1101 16201

CFTR-lntron2-

- AUAUCUCCUCUCAGCCACU 19

1102 16202

CFTR-lntron2-

- AAUAUCUCCUCUCAGCCACU 20

1103 16203

CFTR-lntron2-

- AGAAUAUCUCCUCUCAGCCACU 22

1104 16204

CFTR-lntron2-

- UAGAAUAUCUCCUCUCAGCCACU 23

1105 16205

CFTR-lntron2-

- CAUAUUUAGCUUCUUACU 18

1106 16206

CFTR-lntron2-

- CCAUAUUUAGCUUCUUACU 19

1107 16207

CFTR-lntron2-

- UCCAUAUUUAGCUUCUUACU 20

1108 16208

CFTR-lntron2-

- CUCCAUAUUUAGCUUCUUACU 21

1109 16209

CFTR-lntron2-

- UGCUCCAUAUUUAGCUUCUUACU 23

1110 16210

CFTR-lntron2-

- CUGCUCCAUAUUUAGCUUCUUACU 24

1111 16211

CFTR-lntron2-

- UGUAUUGCCUUGCUCUCU 18

1112 16212

CFTR-lntron2-

- CUGUAUUGCCUUGCUCUCU 19

1113 16213

CFTR-lntron2-

- UCUGUAUUGCCUUGCUCUCU 20

399 15499

474

5535.1 CFTR-lntron2-

- AGGUCUGUAUUGCCUUGCUCUCU 23

1114 16214

CFTR-lntron2-

- U CAAAG AAU U AAG CU AG U 18

1115 16215

CFTR-lntron2-

- U U CAAAG AAU U AAG CU AG U 19

1116 16216

CFTR-lntron2-

- AUUCAAAGAAUUAAGCUAGU 20

404 15504

CFTR-lntron2-

- UAUUCAAAGAAUUAAGCUAGU 21

1117 16217

CFTR-lntron2-

- UU AUUCAAAGAAUUAAGCUAGU 22

1118 16218

CFTR-lntron2-

- U U U AU U CAAAG AAU U AAG CU AG U 23

1119 16219

CFTR-lntron2-

- U U U U AU U CAAAG AAU U AAG CU AG U 24

1120 16220

CFTR-lntron2-

- CCG U U CCAAG AU UG U AG U 18

1121 16221

CFTR-lntron2-

- U CCG U U CCAAG AU UG U AG U 19

1122 16222

CFTR-lntron2-

- AUCCGUUCCAAGAUUGUAGU 20

1123 16223

CFTR-lntron2-

- CAU CCG U U CCAAG AU UG U AG U 21

1124 16224

CFTR-lntron2-

- ACAUCCGUUCCAAGAUUGUAGU 22

1125 16225

CFTR-lntron2-

- CACAUCCGUUCCAAGAUUGUAGU 23

1126 16226

CFTR-lntron2-

- ACACAUCCGUUCCAAGAUUGUAGU 24

1127 16227

CFTR-lntron2-

- CCUUUCCAAUCAAAAGGU 18

1128 16228

CFTR-lntron2-

- U CC U U U CC AAU CAAAAG G U 19

1129 16229

CFTR-lntron2-

- UU CCUUUCCAAUCAAAAGGU 20

1130 16230

CFTR-lntron2-

- UUUCCUUUCCAAUCAAAAGGU 21

1131 16231

CFTR-lntron2-

- AGUUUCCUUUCCAAUCAAAAGGU 23

1132 16232

CFTR-lntron2-

- CAGUUUCCUUUCCAAUCAAAAGGU 24

1133 16233

475

5535.1 CFTR-lntron2-

- CCCGGCCUAUUACUCCUU 18

1134 16234

CFTR-lntron2-

- CCCCGGCCUAUUACUCCUU 19

1135 16235

CFTR-lntron2-

- UGCCCCGGCCUAUUACUCCUU 21

1136 16236

CFTR-lntron2-

- CUGCCCCGGCCUAUUACUCCUU 22

1137 16237

CFTR-lntron2-

- ACUGCCCCGGCCUAUUACUCCUU 23

1138 16238

CFTR-lntron2-

- CACUGCCCCGGCCUAUUACUCCUU 24

1139 16239

CFTR-lntron2-

- UCUGAGUAACCAAAUGUU 18

1140 16240

CFTR-lntron2-

- CUCUGAGUAACCAAAUGUU 19

1141 16241

CFTR-lntron2-

- ACUCUGAGUAACCAAAUGUU 20

1142 16242

CFTR-lntron2-

- UACUCUGAGUAACCAAAUGUU 21

1143 16243

CFTR-lntron2-

- UUACUCUGAGUAACCAAAUGUU 22

1144 16244

CFTR-lntron2-

- CUUACUCUGAGUAACCAAAUGUU 23

1145 16245

CFTR-lntron2-

- UCUUACUCUGAGUAACCAAAUGUU 24

1146 16246

CFTR-lntron2-

- UCAGGAUAUGAACUUUUU 18

1147 16247

CFTR-lntron2-

- AGUCAGGAUAUGAACUUUUU 20

1148 16248

CFTR-lntron2-

- UAGUCAGGAUAUGAACUUUUU 21

1149 16249

CFTR-lntron2-

- UGUAGUCAGGAUAUGAACUUUUU 23

1150 16250

CFTR-lntron2-

- UUGUAGUCAGGAUAUGAACUUUUU 24

1151 16251

Table 38C provides exemplary targeting domains for correcting a mutation (e.g., 3272- 26->G) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within intron 2, start with a 5'G and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through

476

5535.1 complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 38C

477

5535.1 CFTR-lntron2-

+ GUGGGCAGAUCACUUGAGGUC 21

1169 16269

CFTR-lntron2-

+ GGUGGGCAGAUCACUUGAGGUC 22

1170 16270

CFTR-lntron2-

+ GCUACUCGAGAGGCUGAGGCAG 22

1171 16271

CFTR-lntron2-

+ GAUUCGCUUGAACCCAGGAGG 21

1172 16272

CFTR-lntron2-

+ GAGAUUCGCUUGAACCCAGGAGG 23

1173 16273

CFTR-lntron2-

+ GAGAUAAUGAUGCUUUCCACU 21

1174 16274

CFTR-lntron2-

+ GCCCUAUUCUAGGCACUU 18

1175 16275

CFTR-lntron2-

+ GGCCCUAUUCUAGGCACUU 19

1176 16276

CFTR-lntron2-

+ GCCAGGCCCUAUUCUAGGCACUU 23

1177 16277

CFTR-lntron2-

- GCAAACUCUGCCUCCUGGGUUCAA 24

1178 16278

CFTR-lntron2-

- GGCUAAUUUUUGUAGAGA 18

1179 16279

CFTR-lntron2-

- GCCUGGCUAAUUUUUGUAGAGA 22

1180 16280

CFTR-lntron2-

- GGCCUGGCUAAUUUUUGUAGAGA 23

1181 16281

CFTR-lntron2-

- GUUGCUGUUGUUUUUGAGA 19

1182 16282

CFTR-lntron2-

- GUUGUUGCUGUUGUUUUUGAGA 22

1183 16283

CFTR-lntron2-

- GUGUUGUUUGUUUUUGAGA 19

1184 16284

CFTR-lntron2-

- GUUUGUGUUGUUUGUUUUUGAGA 23

1185 16285

CFTR-lntron2-

- GUUUUGUUUUUUAUUUUUUA 20

1186 16286

CFTR-lntron2-

- GUUUAUGAUGUAUCCCCAAGUGCC 24

1187 16287

CFTR-lntron2-

- GUCUCGCUGUGUCACCCAGGC 21

1188 16288

CFTR-lntron2-

- GAGUCUCGCUGUGUCACCCAGGC 23

1189 16289

478

5535.1 CFTR-lntron2-

- GUCUUGCUCUGUUGCCCAGGC 21

1190 16290

CFTR-lntron2-

- GAGUCUUGCUCUGUUGCCCAGGC 23

1191 16291

CFTR-lntron2-

- GCCCACCUUGGCCUCCCAAAAUGC 24

1192 16292

CFTR-lntron2-

- GAUUCUCCUGCCUCAGCCUC 20

1193 16293

CFTR-lntron2-

- GUGAUUCUCCUGCCUCAGCCUC 22

1194 16294

CFTR-lntron2-

- GCUCACUGCAAACUCUGCCUC 21

1195 16295

CFTR-lntron2-

- GUUCAAGCGAAUCUCAGUCUC 21

1196 16296

CFTR-lntron2-

- GGUUCAAGCGAAUCUCAGUCUC 22

1197 16297

CFTR-lntron2-

- GGGUUCAAGCGAAUCUCAGUCUC 23

1198 16298

CFTR-lntron2-

- GCUCACUGCAAACUUCGUCUC 21

1199 16299

CFTR-lntron2-

- GGCUCACUGCAAACUUCGUCUC 22

1200 16300

CFTR-lntron2-

- GAUAAAAGGGUGAGUGAAG 19

1201 16301

CFTR-lntron2-

- GCCUCAGCCUCUCGAGUAG 19

1202 16302

CFTR-lntron2-

- GGCCUGAUGCCAGAUAAAAGG 21

1203 16303

CFTR-lntron2-

- GAAAUUUAUUGAAAUAUUUUGG 22

1204 16304

CFTR-lntron2-

- GAGAACAUGAAUCUGAAUUUG 21

1205 16305

CFTR-lntron2-

- GUAUAUACUCAAUAAAUAUUUG 22

1206 16306

CFTR-lntron2-

- GGUAUAUACUCAAUAAAUAUUUG 23

1207 16307

CFTR-lntron2-

- GGCCAGAUAGAGAACAUGAAU 21

1208 16308

CFTR-lntron2-

- GCUGAGGGAAUGAUUAAU 18

1209 16309

CFTR-lntron2-

- GAGCCACUAUGCCCAGCU 18

1210 16310

479

5535.1 CFTR-lntron2-

- GUGAGCCACUAUGCCCAGCU 20

1211 16311

CFTR-lntron2-

- GUGUGAGCCACUAUGCCCAGCU 22

1212 16312

CFTR-lntron2-

- GGUGUGAGCCACUAUGCCCAGCU 23

1213 16313

CFTR-lntron2-

- GUGCAAAUGCCAUGAGGU 18

1214 16314

CFTR-lntron2-

- GUGUGCAAAUGCCAUGAGGU 20

472 15572

CFTR-lntron2-

- GUGUGUGCAAAUGCCAUGAGGU 22

1215 16315

CFTR-lntron2-

- GGUGUGUGCAAAUGCCAUGAGGU 23

1216 16316

CFTR-lntron2-

- GCCUUGGCCUCCCAAAGUGU 20

474 15574

CFTR-lntron2-

- GCCCGCCUUGGCCUCCCAAAGUGU 24

1217 16317

Table 38D provides exemplary targeting domains for correcting a mutation (e.g., 3272- 26->G) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within intron 2, and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 38D

480

5535.1 CFTR-lntron2-

+ UAUUUACUUAAGCUAGUAAA 20

1223 16323

CFTR-lntron2-

+ AUAGGUAUAUUUUUUAAA 18

1224 16324

CFTR-lntron2-

+ AAUAGGUAUAUUUUUUAAA 19

1225 16325

CFTR-lntron2-

+ AAAU AGG UAUAUUUUU U AAA 20

1226 16326

CFTR-lntron2-

+ AAAAU AGG UAUAUUUUU U AAA 21

1227 16327

CFTR-lntron2-

+ U AAAAU AGG UAUAUUUUU U AAA 22

1228 16328

CFTR-lntron2-

+ AG U AAAAU AGG UAUAUUUUU U AAA 24

1229 16329

CFTR-lntron2-

+ UCUGUCACUGGCAAUCAA 18

1230 16330

CFTR-lntron2-

+ UUCUGUCACUGGCAAUCAA 19

1231 16331

CFTR-lntron2-

+ UUUCUGUCACUGGCAAUCAA 20

1232 16332

CFTR-lntron2-

+ UGGGUUUCUGUCACUGGCAAUCAA 24

1233 16333

CFTR-lntron2-

+ UUCUCCAUCAAAGGAGAA 18

1234 16334

CFTR-lntron2-

+ CUUCUCCAUCAAAGGAGAA 19

1235 16335

CFTR-lntron2-

+ CCUUCUCCAUCAAAGGAGAA 20

1236 16336

CFTR-lntron2-

+ AUGAAAGAAAAAAUAGAA 18

1237 16337

CFTR-lntron2-

+ UAUGAAAGAAAAAAUAGAA 19

1238 16338

CFTR-lntron2-

+ CUAUGAAAGAAAAAAUAGAA 20

614 15714

CFTR-lntron2-

+ AG C U A U G A A AG A A A A A A U AG A A 22

1239 16339

CFTR-lntron2-

+ UAGCUAUGAAAGAAAAAAUAGAA 23

1240 16340

CFTR-lntron2-

+ U UAGCUAUGAAAGAAAAAAUAGAA 24

1241 16341

CFTR-lntron2-

+ AAA U G CCA A A A A A AG G A A 18

1242 16342

481

5535.1 CFTR-lntron2-

+ A A A A U G C C A A A A A AAG G A A 19

1243 16343

CFTR-lntron2-

+ C A A A A U G CCA A A A A A AG G A A 20

1244 16344

CFTR-lntron2-

+ U C A A A A U G CCA A A A A A AG G A A 21

1245 16345

CFTR-lntron2-

+ U U C A A A A U G CCA A A A A A AG G A A 22

1246 16346

CFTR-lntron2-

+ CUUCAAAAUGCCAAAAAAAGGAA 23

1247 16347

CFTR-lntron2-

+ CCUUCAAAAUGCCAAAAAAAGGAA 24

1248 16348

CFTR-lntron2-

+ AACAAACAAAAAACAUAA 18

1249 16349

CFTR-lntron2-

+ AAACAAACAAAAAACAUAA 19

1250 16350

CFTR-lntron2-

+ CAAACAAACAAAAAACAUAA 20

616 15716

CFTR-lntron2-

+ ACAAACAAACAAAAAACAUAA 21

1251 16351

CFTR-lntron2-

+ CACAAACAAACAAAAAACAUAA 22

1252 16352

CFTR-lntron2-

+ ACACAAACAAACAAAAAACAUAA 23

1253 16353

CFTR-lntron2-

+ AACACAAACAAACAAAAAACAUAA 24

1254 16354

CFTR-lntron2-

+ U UAU AAG AAAAG AAG UAA 18

1255 16355

CFTR-lntron2-

+ U U UAU AAG AAAAG AAG UAA 19

1256 16356

CFTR-lntron2-

+ U U U UAU AAG AAAAG AAG UAA 20

1257 16357

CFTR-lntron2-

+ AU U U UAU AAG AAAAG AAG UAA 21

1258 16358

CFTR-lntron2-

+ AAUUU UAU AAG AAAAG AAG UAA 22

1259 16359

CFTR-lntron2-

+ CAAU U U UAU AAG AAAAG AAG UAA 23

1260 16360

CFTR-lntron2-

+ CCAAU U U UAU AAG AAAAG AAG UAA 24

1261 16361

CFTR-lntron2-

+ AGUAGAGAGACCAGGAGAGCA 21

1262 16362

482

5535.1 CFTR-lntron2-

+ AAGUAGAGAGACCAGGAGAGCA 22

1263 16363

CFTR-lntron2-

+ UGAAGUAGAGAGACCAGGAGAGCA 24

1264 16364

CFTR-lntron2-

+ AUCAGAUGGGAAAGCCAAGGA 21

1265 16365

CFTR-lntron2-

+ UGGAUCAGAUGGGAAAGCCAAGGA 24

1266 16366

CFTR-lntron2-

+ UCAUUCAACAAAUAUUUA 18

1267 16367

CFTR-lntron2-

+ UUCAUUCAACAAAUAUUUA 19

1268 16368

CFTR-lntron2-

+ AUUCAUUCAACAAAUAUUUA 20

1269 16369

CFTR-lntron2-

+ UGG AU U CAU U CAACAAAU AU U U A 23

1270 16370

CFTR-lntron2-

+ AUGGAUUCAUUCAACAAAUAUUUA 24

1271 16371

CFTR-lntron2-

+ ACACCACUACACUCCAGC 18

1272 16372

CFTR-lntron2-

+ CACACCACUACACUCCAGC 19

1273 16373

CFTR-lntron2-

+ UCACACCACUACACUCCAGC 20

1274 16374

CFTR-lntron2-

+ AUCACACCACUACACUCCAGC 21

1275 16375

CFTR-lntron2-

+ AGAUCACACCACUACACUCCAGC 23

1276 16376

CFTR-lntron2-

+ CGGGCAGAUCACUUGAGGUC 20

667 15767

CFTR-lntron2-

+ AGGCGGGCAGAUCACUUGAGGUC 23

1277 16377

CFTR-lntron2-

+ AAGGCGGGCAGAUCACUUGAGGUC 24

1278 16378

CFTR-lntron2-

+ UGGGCAGAUCACUUGAGGUC 20

668 15768

CFTR-lntron2-

+ AGGUGGGCAGAUCACUUGAGGUC 23

1279 16379

CFTR-lntron2-

+ AAGGUGGGCAGAUCACUUGAGGUC 24

1280 16380

CFTR-lntron2-

+ CUCGAGAGGCUGAGGCAG 18

1281 16381

483

5535.1 CFTR-lntron2-

+ ACUCGAGAGGCUGAGGCAG 19

1282 16382

CFTR-lntron2-

+ UACUCGAGAGGCUGAGGCAG 20

1283 16383

CFTR-lntron2-

+ CUACUCGAGAGGCUGAGGCAG 21

1284 16384

CFTR-lntron2-

+ AGCU ACUCGAGAGGCUGAGGCAG 23

1285 16385

CFTR-lntron2-

+ CAGCUACUCGAGAGGCUGAGGCAG 24

1286 16386

CFTR-lntron2-

+ CCUGAGGAGAAGGCAAGGUCG 21

1287 16387

CFTR-lntron2-

+ ACCUGAGGAGAAGGCAAGGUCG 22

1288 16388

CFTR-lntron2-

+ UACCUGAGGAGAAGGCAAGGUCG 23

1289 16389

CFTR-lntron2-

+ UUACCUGAGGAGAAGGCAAGGUCG 24

1290 16390

CFTR-lntron2-

+ UCGCUUGAACCCAGGAGG 18

1291 16391

CFTR-lntron2-

+ UUCGCUUGAACCCAGGAGG 19

1292 16392

CFTR-lntron2-

+ AUUCGCUUGAACCCAGGAGG 20

1293 16393

CFTR-lntron2-

+ AGAUUCGCUUGAACCCAGGAGG 22

1294 16394

CFTR-lntron2-

+ UGAGAUUCGCUUGAACCCAGGAGG 24

1295 16395

CFTR-lntron2-

+ UUUUUAAAUUGAAUCAACAUG 21

1296 16396

CFTR-lntron2-

+ UUUUUUAAAUUGAAUCAACAUG 22

1297 16397

CFTR-lntron2-

+ AU U U U U U AAAU UG AAU CAACAUG 23

1298 16398

CFTR-lntron2-

+ U AU U U U U U AAAU UG AAU CAACAUG 24

1299 16399

CFTR-lntron2-

+ AAUUAGCCAGGCAUUGUG 18

1300 16400

CFTR-lntron2-

+ AAAUUAGCCAGGCAUUGUG 19

1301 16401

CFTR-lntron2-

+ AAAAUUAGCCAGGCAUUGUG 20

1302 16402

484

5535.1 CFTR-lntron2-

+ A A A A A UUAGCCAGGCAUUGUG 21

1303 16403

CFTR-lntron2-

+ C A A A A A UUAGCCAGGCAUUGUG 22

1304 16404

CFTR-lntron2-

+ ACAAAAAUUAGCCAGGCAUUGUG 23

1305 16405

CFTR-lntron2-

+ UACAAAAAUUAGCCAGGCAUUGUG 24

1306 16406

CFTR-lntron2-

+ AAUGCCACCAGGUGGCAU 18

1307 16407

CFTR-lntron2-

+ AAAUGCCACCAGGUGGCAU 19

1308 16408

CFTR-lntron2-

+ CAAAUGCCACCAGGUGGCAU 20

1309 16409

CFTR-lntron2-

+ AGAGAUAAUGAUGCUUUCCACU 22

1310 16410

CFTR-lntron2-

+ UAGAGAUAAUGAUGCUUUCCACU 23

1311 16411

CFTR-lntron2-

+ AUAGAGAUAAUGAUGCUUUCCACU 24

1312 16412

CFTR-lntron2-

+ UAUAUUUUCUAUUAUAGU 18

1313 16413

CFTR-lntron2-

+ AUAUAUUUUCUAUUAUAGU 19

1314 16414

CFTR-lntron2-

+ UAUAUAUUUUCUAUUAUAGU 20

1315 16415

CFTR-lntron2-

+ UUAUAUAUUUUCUAUUAUAGU 21

1316 16416

CFTR-lntron2-

+ AUUAUAUAUUUUCUAUUAUAGU 22

1317 16417

CFTR-lntron2-

+ AAUUAUAUAUUUUCUAUUAUAGU 23

1318 16418

CFTR-lntron2-

+ AAAUUAUAUAUUUUCUAUUAUAGU 24

1319 16419

CFTR-lntron2-

+ A C A A A A A U A A U AG A ACG U 18

1320 16420

CFTR-lntron2-

+ AACAAAAAU AAU AG AACG U 19

1321 16421

CFTR-lntron2-

+ AAACAAAAAUAAUAGAACGU 20

1322 16422

CFTR-lntron2-

+ AAAACAAAAAU AAU AG AACG U 21

1323 16423

485

5535.1 CFTR-lntron2-

+ CAAAACAAAAAUAAUAGAACGU 22

1324 16424

CFTR-lntron2-

+ ACAAAACAAAAAU AAU AG AACG U 23

1325 16425

CFTR-lntron2-

+ AACAAAACAAAAAUAAUAGAACGU 24

1326 16426

CFTR-lntron2-

+ AGGCCCUAUUCUAGGCACUU 20

718 15818

CFTR-lntron2-

+ CAGGCCCUAUUCUAGGCACUU 21

1327 16427

CFTR-lntron2-

+ CCAGGCCCUAUUCUAGGCACUU 22

1328 16428

CFTR-lntron2-

+ UGCCAGGCCCUAUUCUAGGCACUU 24

1329 16429

CFTR-lntron2-

- UCUGCCUCCUGGGUUCAA 18

1330 16430

CFTR-lntron2-

- CUCUGCCUCCUGGGUUCAA 19

1331 16431

CFTR-lntron2-

- ACUCUGCCUCCUGGGUUCAA 20

1332 16432

CFTR-lntron2-

- AACUCUGCCUCCUGGGUUCAA 21

1333 16433

CFTR-lntron2-

- AAACUCUGCCUCCUGGGUUCAA 22

1334 16434

CFTR-lntron2-

- CAAACUCUGCCUCCUGGGUUCAA 23

1335 16435

CFTR-lntron2-

- UGAAUAUCUAAGUUUUAA 18

1336 16436

CFTR-lntron2-

- UUGAAUAUCUAAGUUUUAA 19

1337 16437

CFTR-lntron2-

- UUUGAAUAUCUAAGUUUUAA 20

1338 16438

CFTR-lntron2-

- UUUUAUUGAUUUUAUUCA 18

1339 16439

CFTR-lntron2-

- UUUUUAUUGAUUUUAUUCA 19

1340 16440

CFTR-lntron2-

- AUUUUUAUUGAUUUUAUUCA 20

1341 16441

CFTR-lntron2-

- UAUUUUUAUUGAUUUUAUUCA 21

1342 16442

CFTR-lntron2-

- UUAUUUUUAUUGAUUUUAUUCA 22

1343 16443

486

5535.1 CFTR-lntron2-

- UUUAUUUUUAUUGAUUUUAUUCA 23

1344 16444

CFTR-lntron2-

- CUUUAUUUUUAUUGAUUUUAUUCA 24

1345 16445

CFTR-lntron2-

- AAUACACAUUUGGUUUCA 18

1346 16446

CFTR-lntron2-

- AAAUACACAUUUGGUUUCA 19

1347 16447

CFTR-lntron2-

- AAAAU ACACAU UUGGUUUCA 20

1348 16448

CFTR-lntron2-

- UGGCUAAUUUUUGUAGAGA 19

1349 16449

CFTR-lntron2-

- CUGGCUAAUUUUUGUAGAGA 20

626 15726

CFTR-lntron2-

- CCUGGCUAAUUUUUGUAGAGA 21

1350 16450

CFTR-lntron2-

- AGGCCUGGCUAAUUUUUGUAGAGA 24

1351 16451

CFTR-lntron2-

- UUGCUGUUGUUUUUGAGA 18

1352 16452

CFTR-lntron2-

- UGUUGCUGUUGUUUUUGAGA 20

1353 16453

CFTR-lntron2-

- UUGUUGCUGUUGUUUUUGAGA 21

1354 16454

CFTR-lntron2-

- UGUUGUUGCUGUUGUUUUUGAGA 23

1355 16455

CFTR-lntron2-

- UUGUUGUUGCUGUUGUUUUUGAGA 24

1356 16456

CFTR-lntron2-

- UGUUGUUUGUUUUUGAGA 18

1357 16457

CFTR-lntron2-

- UGUGUUGUUUGUUUUUGAGA 20

1358 16458

CFTR-lntron2-

- UUGUGUUGUUUGUUUUUGAGA 21

1359 16459

CFTR-lntron2-

- UUUGUGUUGUUUGUUUUUGAGA 22

1360 16460

CFTR-lntron2-

- UGUUUGUGUUGUUUGUUUUUGAGA 24

1361 16461

CFTR-lntron2-

- U AG CU UAAG U AAA U A A A AG G A 21

1362 16462

CFTR-lntron2-

- CUAGCUUAAGU AAA U A A A AG G A 22

1363 16463

487

5535.1 CFTR-lntron2-

- ACUAGCUUAAGUAAAUAAAAGGA 23

1364 16464

CFTR-lntron2-

- UACUAGCUUAAGUAAAUAAAAGGA 24

1365 16465

CFTR-lntron2-

- UGUUGAAUGAAUCCAUGA 18

1366 16466

CFTR-lntron2-

- UUGUUGAAUGAAUCCAUGA 19

1367 16467

CFTR-lntron2-

- UUUGUUGAAUGAAUCCAUGA 20

628 15728

CFTR-lntron2-

- AUUUGUUGAAUGAAUCCAUGA 21

1368 16468

CFTR-lntron2-

- UAUUUGUUGAAUGAAUCCAUGA 22

1369 16469

CFTR-lntron2-

- AUAUUUGUUGAAUGAAUCCAUGA 23

1370 16470

CFTR-lntron2-

- AAUAUUUGUUGAAUGAAUCCAUGA 24

1371 16471

CFTR-lntron2-

- UCAAUAAAUAUUUGUUGA 18

1372 16472

CFTR-lntron2-

- CUCAAUAAAUAUUUGUUGA 19

1373 16473

CFTR-lntron2-

- ACUCAAUAAAUAUUUGUUGA 20

1374 16474

CFTR-lntron2-

- UACUCAAUAAAUAUUUGUUGA 21

1375 16475

CFTR-lntron2-

- AUACUCAAUAAAUAUUUGUUGA 22

1376 16476

CFTR-lntron2-

- UAUACUCAAUAAAUAUUUGUUGA 23

1377 16477

CFTR-lntron2-

- AUAUACUCAAUAAAUAUUUGUUGA 24

1378 16478

CFTR-lntron2-

- UUUGUUUUUUAUUUUUUA 18

1379 16479

CFTR-lntron2-

- UUUUGUUUUUUAUUUUUUA 19

1380 16480

CFTR-lntron2-

- UGUUUUGUUUUUUAUUUUUUA 21

1381 16481

CFTR-lntron2-

- UUGUUUUGUUUUUUAUUUUUUA 22

1382 16482

CFTR-lntron2-

- UUUGUUUUGUUUUUUAUUUUUUA 23

1383 16483

488

5535.1 CFTR-lntron2-

- CUUUGUUUUGUUUUUUAUUUUUUA 24

1384 16484

CFTR-lntron2-

- UAUGAUGUAUCCCCAAGUGCC 21

1385 16485

CFTR-lntron2-

- UUAUGAUGUAUCCCCAAGUGCC 22

1386 16486

CFTR-lntron2-

- UUUAUGAUGUAUCCCCAAGUGCC 23

1387 16487

CFTR-lntron2-

- UCGCUGUGUCACCCAGGC 18

1388 16488

CFTR-lntron2-

- CUCGCUGUGUCACCCAGGC 19

1389 16489

CFTR-lntron2-

- UCUCGCUGUGUCACCCAGGC 20

658 15758

CFTR-lntron2-

- AGUCUCGCUGUGUCACCCAGGC 22

1390 16490

CFTR-lntron2-

- AGAGUCUCGCUGUGUCACCCAGGC 24

1391 16491

CFTR-lntron2-

- UUGCUCUGUUGCCCAGGC 18

1392 16492

CFTR-lntron2-

- CUUGCUCUGUUGCCCAGGC 19

1393 16493

CFTR-lntron2-

- UCUUGCUCUGUUGCCCAGGC 20

659 15759

CFTR-lntron2-

- AGUCUUGCUCUGUUGCCCAGGC 22

1394 16494

CFTR-lntron2-

- AGAGUCUUGCUCUGUUGCCCAGGC 24

1395 16495

CFTR-lntron2-

- CUUGGCCUCCCAAAAUGC 18

1396 16496

CFTR-lntron2-

- CCUUGGCCUCCCAAAAUGC 19

1397 16497

CFTR-lntron2-

- ACCUUGGCCUCCCAAAAUGC 20

663 15763

CFTR-lntron2-

- CACCUUGGCCUCCCAAAAUGC 21

1398 16498

CFTR-lntron2-

- CCACCUUGGCCUCCCAAAAUGC 22

1399 16499

CFTR-lntron2-

- CCCACCUUGGCCUCCCAAAAUGC 23

1400 16500

CFTR-lntron2-

- UUCUCCUGCCUCAGCCUC 18

1401 16501

489

5535.1 CFTR-lntron2-

- AUUCUCCUGCCUCAGCCUC 19

1402 16502

CFTR-lntron2-

- UGAUUCUCCUGCCUCAGCCUC 21

1403 16503

CFTR-lntron2-

- AGUGAUUCUCCUGCCUCAGCCUC 23

1404 16504

CFTR-lntron2-

- AAGUGAUUCUCCUGCCUCAGCCUC 24

1405 16505

CFTR-lntron2-

- CACUGCAAACUCUGCCUC 18

1406 16506

CFTR-lntron2-

- UCACUGCAAACUCUGCCUC 19

1407 16507

CFTR-lntron2-

- CUCACUGCAAACUCUGCCUC 20

1408 16508

CFTR-lntron2-

- AGCUCACUGCAAACUCUGCCUC 22

1409 16509

CFTR-lntron2-

- CAGCUCACUGCAAACUCUGCCUC 23

1410 16510

CFTR-lntron2-

- UCAGCUCACUGCAAACUCUGCCUC 24

1411 16511

CFTR-lntron2-

- CAAGCGAAUCUCAGUCUC 18

1412 16512

CFTR-lntron2-

- UCAAGCGAAUCUCAGUCUC 19

1413 16513

CFTR-lntron2-

- UUCAAGCGAAUCUCAGUCUC 20

1414 16514

CFTR-lntron2-

- UGGGUUCAAGCGAAUCUCAGUCUC 24

1415 16515

CFTR-lntron2-

- CACUGCAAACUUCGUCUC 18

1416 16516

CFTR-lntron2-

- UCACUGCAAACUUCGUCUC 19

1417 16517

CFTR-lntron2-

- CUCACUGCAAACUUCGUCUC 20

1418 16518

CFTR-lntron2-

- UGGCUCACUGCAAACUUCGUCUC 23

1419 16519

CFTR-lntron2-

- UUGGCUCACUGCAAACUUCGUCUC 24

1420 16520

CFTR-lntron2-

- UCUCCUUUGAUGGAGAAG 18

1421 16521

CFTR-lntron2-

- UUCUCCUUUGAUGGAGAAG 19

1422 16522

490

5535.1 CFTR-lntron2-

- UUUCUCCUUUGAUGGAGAAG 20

1423 16523

CFTR-lntron2-

- AUAAAAGGGUGAGUGAAG 18

1424 16524

CFTR-lntron2-

- AGAUAAAAGGGUGAGUGAAG 20

672 15772

CFTR-lntron2-

- CCUCAGCCUCUCGAGUAG 18

1425 16525

CFTR-lntron2-

- UGCCUCAGCCUCUCGAGUAG 20

1426 16526

CFTR-lntron2-

- CUGCCUCAGCCUCUCGAGUAG 21

1427 16527

CFTR-lntron2-

- CCUGCCUCAGCCUCUCGAGUAG 22

1428 16528

CFTR-lntron2-

- UCCUGCCUCAGCCUCUCGAGUAG 23

1429 16529

CFTR-lntron2-

- CUCCUGCCUCAGCCUCUCGAGUAG 24

1430 16530

CFTR-lntron2-

- AGGCCUGAUGCCAGAUAAAAGG 22

1431 16531

CFTR-lntron2-

- CAGGCCUGAUGCCAGAUAAAAGG 23

1432 16532

CFTR-lntron2-

- ACAGGCCUGAUGCCAGAUAAAAGG 24

1433 16533

CFTR-lntron2-

- AAAUUUAUUGAAAUAUUUUGG 21

1434 16534

CFTR-lntron2-

- UGAAAUUUAUUGAAAUAUUUUGG 23

1435 16535

CFTR-lntron2-

- UUGAAAUUUAUUGAAAUAUUUUGG 24

1436 16536

CFTR-lntron2-

- UUUGUAUUUUAGUAGAUG 18

1437 16537

CFTR-lntron2-

- UUUUGUAUUUUAGUAGAUG 19

1438 16538

CFTR-lntron2-

- UUUUUGUAUUUUAGUAGAUG 20

688 15788

CFTR-lntron2-

- AUUUUUGUAUUUUAGUAGAUG 21

1439 16539

CFTR-lntron2-

- AAUUUUUGUAUUUUAGUAGAUG 22

1440 16540

CFTR-lntron2-

- UAAUUUUUGUAUUUUAGUAGAUG 23

1441 16541

491

5535.1 CFTR-lntron2-

- CUAAUUUUUGUAUUUUAGUAGAUG 24

1442 16542

CFTR-lntron2-

- AGAGAACAUGAAUCUGAAUUUG 22

1443 16543

CFTR-lntron2-

- UAGAGAACAUGAAUCUGAAUUUG 23

1444 16544

CFTR-lntron2-

- AUAGAGAACAUGAAUCUGAAUUUG 24

1445 16545

CFTR-lntron2-

- AUACUCAAUAAAUAUUUG 18

1446 16546

CFTR-lntron2-

- UAUACUCAAUAAAUAUUUG 19

1447 16547

CFTR-lntron2-

- AUAUACUCAAUAAAUAUUUG 20

1448 16548

CFTR-lntron2-

- UAUAUACUCAAUAAAUAUUUG 21

1449 16549

CFTR-lntron2-

- UGGUAUAUACUCAAUAAAUAUUUG 24

1450 16550

CFTR-lntron2-

- UGGCCAGAUAGAGAACAUGAAU 22

1451 16551

CFTR-lntron2-

- AUGGCCAGAUAGAGAACAUGAAU 23

1452 16552

CFTR-lntron2-

- UAUGGCCAGAUAGAGAACAUGAAU 24

1453 16553

CFTR-lntron2-

- UGCUGAGGGAAUGAUUAAU 19

1454 16554

CFTR-lntron2-

- AUGCUGAGGGAAUGAUUAAU 20

1455 16555

CFTR-lntron2-

- UUGCUUUCAAAACCUUUAUAU 21

1456 16556

CFTR-lntron2-

- UUUGCUUUCAAAACCUUUAUAU 22

1457 16557

CFTR-lntron2-

- AUUUGCUUUCAAAACCUUUAUAU 23

1458 16558

CFTR-lntron2-

- UAUUUGCUUUCAAAACCUUUAUAU 24

1459 16559

CFTR-lntron2-

- UGAGCCACUAUGCCCAGCU 19

1460 16560

CFTR-lntron2-

- UGUGAGCCACUAUGCCCAGCU 21

1461 16561

CFTR-lntron2-

- AGGUGUGAGCCACUAUGCCCAGCU 24

1462 16562

492

5535.1 CFTR-lntron2-

- UGUGCAAAUGCCAUGAGGU 19

1463 16563

CFTR-lntron2-

- UGUGUGCAAAUGCCAUGAGGU 21

1464 16564

CFTR-lntron2-

- UGGUGUGUGCAAAUGCCAUGAGGU 24

1465 16565

CFTR-lntron2-

- CUUGGCCUCCCAAAGUGU 18

1466 16566

CFTR-lntron2-

- CCUUGGCCUCCCAAAGUGU 19

1467 16567

CFTR-lntron2-

- CGCCUUGGCCUCCCAAAGUGU 21

1468 16568

CFTR-lntron2-

- CCGCCUUGGCCUCCCAAAGUGU 22

1469 16569

CFTR-lntron2-

- CCCGCCUUGGCCUCCCAAAGUGU 23

1470 16570

CFTR-lntron2-

- UGUAAAAAUUGUAUAUUU 18

1471 16571

CFTR-lntron2-

- AUGUAAAAAUUGUAUAUUU 19

1472 16572

CFTR-lntron2-

- AAUGUAAAAAUUGUAUAUUU 20

1473 16573

CFTR-lntron2-

- AAAUG U AAAAAU UG U AU AU U U 21

1474 16574

CFTR-lntron2-

- CAAAUG U AAAAAU UG U AU AU U U 22

1475 16575

CFTR-lntron2-

- ACAAAUG U AAAAAU UG U AU AU U U 23

1476 16576

CFTR-lntron2-

- AACAAAUG U AAAAAU UG U AU AU U U 24

1477 16577

Table 3 8E provides exemplary targeting domains for correcting a mutation (e.g., 3272-

26->G) in the CFTR gene selected according to the fifth tier parameters. The targeting domains bind within intron 2, and PAM is NNGRRV. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 38E

493

5535.1 CFTR-

+ C U U C A A A A U G C C A A A A A A 18

lntron2-1478 16578

CFTR-

+ CC U U C A A A A U G C C A A A A A A 19

lntron2-1479 16579

CFTR-

+ G CC U U C A A A A U G C C A A A A A A 20

lntron2-42 15142

CFTR-

+ U G CC U U CAAAAUG CC AAAAAA 21

Intron2-1480 16580

CFTR-

+ UUGCCUUCAAAAUGCCAAAAAA 22

lntron2-1481 16581

CFTR-

+ UUUGCCUUCAAAAUGCCAAAAAA 23

lntron2-1482 16582

CFTR-

+ CUUUGCCUUCAAAAUGCCAAAAAA 24

lntron2-1483 16583

CFTR-

+ CCU U CAAAAUG CCAAAAA 18

lntron2-1484 16584

CFTR-

+ GCCUUCAAAAUGCCAAAAA 19

lntron2-1485 16585

CFTR-

+ U G CC U U CAAAAUG CCAAAAA 20

lntron2-1486 16586

CFTR-

+ U U G CC U U C A A A A U G C C A A A A A 21

lntron2-1487 16587

CFTR-

+ UUUGCCUUCAAAAUGCCAAAAA 22

lntron2-1488 16588

CFTR-

+ CUUUGCCUUCAAAAUGCCAAAAA 23

lntron2-1489 16589

CFTR-

+ ACUUUGCCUUCAAAAUGCCAAAAA 24

Intron2-1490 16590

CFTR-

+ CAAUCCAUGGU C AC A A A A 18

lntron2-1491 16591

CFTR-

+ UCAAUCCAUGGUCACAAAA 19

lntron2-1492 16592

CFTR-

+ UUCAAUCCAUGGUCACAAAA 20

lntron2-1493 16593

CFTR-

+ AUUCAAUCCAUGGUCACAAAA 21

lntron2-1494 16594

CFTR-

+ GAUUCAAUCCAUGGUCACAAAA 22

lntron2-1495 16595

CFTR-

+ GGAUUCAAUCCAUGGUCACAAAA 23

lntron2-1496 16596

CFTR-

+ AGGAUUCAAUCCAUGGUCACAAAA 24

lntron2-1497 16597

494

5535.1 CFTR-

+ UGGGGGAUACAGUGAAAA 18

lntron2-1498 16598

CFTR-

+ AUGGGGGAUACAGUGAAAA 19

lntron2-1499 16599

CFTR-

+ CAUGGGGGAUACAGUGAAAA 20

Intron2-1500 16600

CFTR-

+ ACAUGGGGGAUACAGUGAAAA 21

Intron2-1501 16601

CFTR-

+ AACAUGGGGGAUACAGUGAAAA 22

Intron2-1502 16602

CFTR-

+ CAA CAUGGGGGAUACAGUGAAAA 23

Intron2-1503 16603

CFTR-

+ UCAACAUGGGGGAUACAGUGAAAA 24

Intron2-1504 16604

CFTR-

+ AUUAAAGGUCUUUGAAAA 18

Intron2-1505 16605

CFTR-

+ UAUUAAAGGUCUUUGAAAA 19

Intron2-1506 16606

CFTR-

+ GU AUUAAAGGUCUUUGAAAA 20

Intron2-1507 16607

CFTR-

+ UGUAUUAAAGGUCUUUGAAAA 21

Intron2-1508 16608

CFTR-

+ AUGUAUUAAAGGUCUUUGAAAA 22

Intron2-1509 16609

CFTR-

+ CAUGUAUUAAAGGUCUUUGAAAA 23

Intron2-1510 16610

CFTR-

+ UCAUGUAUUAAAGGUCUUUGAAAA 24

lntron2-1511 16611

CFTR-

+ GUUUGCUUUUCUGUAAAA 18

lntron2-1512 16612

CFTR-

+ AGUUUGCUUUUCUGUAAAA 19

lntron2-1513 16613

CFTR-

+ CAGUUUGCUUUUCUGUAAAA 20

lntron2-1514 16614

CFTR-

+ UCAGUUUGCUUUUCUGUAAAA 21

lntron2-1515 16615

CFTR-

+ CUCAGUUUGCUUUUCUGUAAAA 22

lntron2-1516 16616

CFTR-

+ CCUCAGUUUGCUUUUCUGUAAAA 23

lntron2-1517 16617

CFTR-

+ GCCUCAGUUUGCUUUUCUGUAAAA 24

lntron2-1518 16618

495

5535.1 CFTR-

+ UUUUGAUUGGAAAGGAAA 18

lntron2-1519 16619

CFTR-

+ CUUUUGAUUGGAAAGGAAA 19

Intron2-1520 16620

CFTR-

+ CCUUUUGAUUGGAAAGGAAA 20

lntron2-1521 16621

CFTR-

+ ACCUUUUGAUUGGAAAGGAAA 21

lntron2-1522 16622

CFTR-

+ AACCUUUUGAUUGGAAAGGAAA 22

lntron2-1523 16623

CFTR-

+ UAACCUUUUGAUUGGAAAGGAAA 23

lntron2-1524 16624

CFTR-

+ CUAACCUUUUGAUUGGAAAGGAAA 24

lntron2-1525 16625

CFTR-

+ GCUGAGAUGUAAAUGAAA 18

lntron2-1526 16626

CFTR-

+ AGCUGAGAUGUAAAUGAAA 19

lntron2-1527 16627

CFTR-

+ GAGCUGAGAUGUAAAUGAAA 20

lntron2-1528 16628

CFTR-

+ GGAGCUGAGAUGUAAAUGAAA 21

lntron2-1529 16629

CFTR-

+ AGGAGCUGAGAUGUAAAUGAAA 22

Intron2-1530 16630

CFTR-

+ CAGGAGCUGAGAUGUAAAUGAAA 23

lntron2-1531 16631

CFTR-

+ UCAGGAGCUGAGAUGUAAAUGAAA 24

lntron2-1532 16632

CFTR-

+ GGGAUACAUCAUAAACAA 18

lntron2-1533 16633

CFTR-

+ GGGGAUACAUCAUAAACAA 19

lntron2-1534 16634

CFTR-

+ UGGGGAUACAUCAUAAACAA 20

lntron2-1535 16635

CFTR-

+ UUGGGGAUACAUCAUAAACAA 21

lntron2-1536 16636

CFTR-

+ CUUGGGGAUACAUCAUAAACAA 22

lntron2-1537 16637

CFTR-

+ ACU UGGGGAUACAUCAUAAACAA 23

lntron2-1538 16638

CFTR-

+ CACUUGGGGAUACAUCAUAAACAA 24

lntron2-1539 16639

496

5535.1 CFTR-

+ ACACUCCAGCCUGGGCAA 18

Intron2-1540 16640

CFTR-

+ UACACUCCAGCCUGGGCAA 19

lntron2-1541 16641

CFTR-

+ UUACACUCCAGCCUGGGCAA 20

lntron2-1542 16642

CFTR-

+ AUUACACUCCAGCCUGGGCAA 21

lntron2-1543 16643

CFTR-

+ CAUUACACUCCAGCCUGGGCAA 22

lntron2-1544 16644

CFTR-

+ CCAUUACACUCCAGCCUGGGCAA 23

lntron2-1545 16645

CFTR-

+ ACCAUUACACUCCAGCCUGGGCAA 24

lntron2-1546 16646

CFTR-

+ ACUCACCUUCUCCAUCAA 18

lntron2-1547 16647

CFTR-

+ GACUCACCUUCUCCAUCAA 19

lntron2-1548 16648

CFTR-

+ AGACUCACCUUCUCCAUCAA 20

lntron2-239 15339

CFTR-

+ CAGACUCACCUUCUCCAUCAA 21

lntron2-1549 16649

CFTR-

+ GCAGACUCACCUUCUCCAUCAA 22

Intron2-1550 16650

CFTR-

+ AGCAGACUCACCUUCUCCAUCAA 23

lntron2-1551 16651

CFTR-

+ GAGCAGACUCACCUUCUCCAUCAA 24

lntron2-1552 16652

CFTR-

+ AU ACCAAU U U U AU AAG AA 18

lntron2-1553 16653

CFTR-

+ AAU ACCAAU U U U AU AAG AA 19

lntron2-1554 16654

CFTR-

+ AAAU ACCAAU U U U AU AAG AA 20

lntron2-1555 16655

CFTR-

+ CAAAU ACCAAU U U U AU AAG AA 21

lntron2-1556 16656

CFTR-

+ U CAAAU ACCAAU U U U AU AAG AA 22

lntron2-1557 16657

CFTR-

+ U U CAAAU ACCAAU U U U AU AAG AA 23

lntron2-1558 16658

CFTR-

+ U U U CAAAU ACCAAU U U U AU AAG AA 24

lntron2-1559 16659

497

5535.1 CFTR-

+ ACCAGGCCCAGAUCAGAA 18

Intron2-1560 16660

CFTR-

+ UACCAGGCCCAGAUCAGAA 19

lntron2-1561 16661

CFTR-

+ AUACCAGGCCCAGAUCAGAA 20

lntron2-242 15342

CFTR-

+ CAU ACCAGGCCCAGAUCAGAA 21

lntron2-1562 16662

CFTR-

+ ACAUACCAGGCCCAGAUCAGAA 22

lntron2-1563 16663

CFTR-

+ CACAUACCAGGCCCAGAUCAGAA 23

lntron2-1564 16664

CFTR-

+ CCACAU ACCAGGCCCAGAUCAGAA 24

lntron2-1565 16665

CFTR-

+ CUAACCUUUUGAUUGGAA 18

lntron2-1566 16666

CFTR-

+ CCUAACCUUUUGAUUGGAA 19

lntron2-1567 16667

CFTR-

+ UCCUAACCUUUUGAUUGGAA 20

lntron2-246 15346

CFTR-

+ AUCCUAACCUUUUGAUUGGAA 21

lntron2-1568 16668

CFTR-

+ GAUCCUAACCUUUUGAUUGGAA 22

lntron2-1569 16669

CFTR-

+ GGAUCCUAACCUUUUGAUUGGAA 23

Intron2-1570 16670

CFTR-

+ AGGAUCCUAACCUUUUGAUUGGAA 24

lntron2-1571 16671

CFTR-

+ UGGCAUAGCAUUGUUGAA 18

lntron2-1572 16672

CFTR-

+ CUGGCAUAGCAUUGUUGAA 19

lntron2-1573 16673

CFTR-

+ ACUGGCAUAGCAUUGUUGAA 20

lntron2-1574 16674

CFTR-

+ UACUGGCAUAGCAUUGUUGAA 21

lntron2-1575 16675

CFTR-

+ GUACUGGCAUAGCAUUGUUGAA 22

lntron2-1576 16676

CFTR-

+ UGUACUGGCAUAGCAUUGUUGAA 23

lntron2-1577 16677

CFTR-

+ UUGUACUGGCAUAGCAUUGUUGAA 24

lntron2-1578 16678

498

5535.1 CFTR-

+ AAAACAAAACAAAAAUAA 18

lntron2-1579 16679

CFTR-

+ CAAAACAAAACAAAAAUAA 19

Intron2-1580 16680

CFTR-

+ ACAAAACAAAACAAAAAUAA 20

lntron2-1581 16681

CFTR-

+ AACAAAACAAAACAAAAAUAA 21

lntron2-1582 16682

CFTR-

+ AAACAAAACAAAACAAAAAUAA 22

lntron2-1583 16683

CFTR-

+ AAAA CAAAACAAAACAAAAAUAA 23

lntron2-1584 16684

CFTR-

+ AAAAACAAAACAAAACAAAAAUAA 24

lntron2-1585 16685

CFTR-

+ A C AC C A AG U G U U C A A U A A 18

lntron2-1586 16686

CFTR-

+ CAC ACC AAG U G U U CAAU AA 19

lntron2-1587 16687

CFTR-

+ ACACACCAAG UG U U CAAU AA 20

lntron2-1588 16688

CFTR-

+ CACACACCAAGUGUUCAAUAA 21

lntron2-1589 16689

CFTR-

+ GCACACACCAAGUGUUCAAUAA 22

Intron2-1590 16690

CFTR-

+ UGCACACACCAAGUGUUCAAUAA 23

lntron2-1591 16691

CFTR-

+ UUGCACACACCAAGUGUUCAAUAA 24

lntron2-1592 16692

CFTR-

+ UCAGGAGCUGAGAUGUAA 18

lntron2-1593 16693

CFTR-

+ UUCAGGAGCUGAGAUGUAA 19

lntron2-1594 16694

CFTR-

+ CUUCAGGAGCUGAGAUGUAA 20

lntron2-1595 16695

CFTR-

+ ACUUCAGGAGCUGAGAUGUAA 21

lntron2-1596 16696

CFTR-

+ UACUUCAGGAGCUGAGAUGUAA 22

lntron2-1597 16697

CFTR-

+ AUACUUCAGGAGCUGAGAUGUAA 23

lntron2-1598 16698

CFTR-

+ CAUACUUCAGGAGCUGAGAUGUAA 24

lntron2-1599 16699

499

5535.1 CFTR-

+ GGAAAUGAAUUUAAUUAA 18

Intron2-1600 16700

CFTR-

+ AGGAAAUGAAUUUAAUUAA 19

Intron2-1601 16701

CFTR-

+ AAGG AAAUG AAU U U AAU U AA 20

Intron2-1602 16702

CFTR-

+ AAAGGAAAUGAAUUUAAUUAA 21

Intron2-1603 16703

CFTR-

+ AAAAGG AAAUG AAU U U AAU U AA 22

Intron2-1604 16704

CFTR-

+ AAAAAGG AAAUG AAU U U AAU U AA 23

Intron2-1605 16705

CFTR-

+ AAAAAAGGAAAUGAAUUUAAUUAA 24

Intron2-1606 16706

CFTR-

+ U U U U AAAU UG AAU CAACA 18

Intron2-1607 16707

CFTR-

+ U U U U U AAAU UG AAU CAACA 19

Intron2-1608 16708

CFTR-

+ U U U U U U AAAU UG AAU CAACA 20

lntron2-621 15721

CFTR-

+ AUUUUUUAAAUUGAAUCAACA 21

Intron2-1609 16709

CFTR-

+ UAUUUUUUAAAUUGAAUCAACA 22

Intron2-1610 16710

CFTR-

+ AUAUUUUU U AAAU UG AAU CAACA 23

lntron2-1611 16711

CFTR-

+ UAUAUUUUU U AAAU UG AAU CAACA 24

lntron2-1612 16712

CFTR-

+ CCACCUUUCUCUCACACA 18

lntron2-1613 16713

CFTR-

+ UCCACCUUUCUCUCACACA 19

lntron2-1614 16714

CFTR-

+ CUCCACCUUUCUCUCACACA 20

lntron2-1615 16715

CFTR-

+ UCUCCACCUUUCUCUCACACA 21

lntron2-1616 16716

CFTR-

+ UUCUCCACCUUUCUCUCACACA 22

lntron2-1617 16717

CFTR-

+ CUUCUCCACCUUUCUCUCACACA 23

lntron2-1618 16718

CFTR-

+ GCUUCUCCACCUUUCUCUCACACA 24

lntron2-1619 16719

500

5535.1 CFTR-

+ UCCAGCCUGGGUGACACA 18

Intron2-1620 16720

CFTR-

+ CUCCAGCCUGGGUGACACA 19

lntron2-1621 16721

CFTR-

+ ACUCCAGCCUGGGUGACACA 20

lntron2-1622 16722

CFTR-

+ CACUCCAGCCUGGGUGACACA 21

lntron2-1623 16723

CFTR-

+ ACACUCCAGCCUGGGUGACACA 22

lntron2-1624 16724

CFTR-

+ UACACUCCAGCCUGGGUGACACA 23

lntron2-1625 16725

CFTR-

+ CUACACUCCAGCCUGGGUGACACA 24

lntron2-1626 16726

CFTR-

+ AAAAU U U CAUG AACCACA 18

lntron2-1627 16727

CFTR-

+ AAAAAU U U CAUG AACCACA 19

lntron2-1628 16728

CFTR-

+ GAAAAAU U U CAUG AACCACA 20

lntron2-455 15555

CFTR-

+ UGAAAAAUUUCAUGAACCACA 21

lntron2-1629 16729

CFTR-

+ AUGAAAAAUUUCAUGAACCACA 22

Intron2-1630 16730

CFTR-

+ GAUGAAAAAUUUCAUGAACCACA 23

lntron2-1631 16731

CFTR-

+ AGAUGAAAAAUUUCAUGAACCACA 24

lntron2-1632 16732

CFTR-

+ G U GAAAAAG U GG U CC AC A 18

lntron2-1633 16733

CFTR-

+ U G U GAAAAAG U GG U CC AC A 19

lntron2-1634 16734

CFTR-

+ AUGUGAAAAAGUGGUCCACA 20

lntron2-256 15356

CFTR-

+ AAUGUGAAAAAGUGGUCCACA 21

lntron2-1635 16735

CFTR-

+ C A A U G U G A A A A AG UGGUCCACA 22

lntron2-1636 16736

CFTR-

+ UCAAUGUGAAAAAGUGGUCCACA 23

lntron2-1637 16737

CFTR-

+ UUCAAUGUGAAAAAGUGGUCCACA 24

lntron2-1638 16738

501

5535.1 CFTR-

+ GCCUUUUUUCUCUUCACA 18

lntron2-1639 16739

CFTR-

+ AGCCUUUUUUCUCUUCACA 19

Intron2-1640 16740

CFTR-

+ AAGCCUUUUUUCUCUUCACA 20

lntron2-1641 16741

CFTR-

+ AAAGCCUUUUUUCUCUUCACA 21

lntron2-1642 16742

CFTR-

+ GAAAGCCUUUUUUCUCUUCACA 22

lntron2-1643 16743

CFTR-

+ UGAAAGCCUUUUUUCUCUUCACA 23

lntron2-1644 16744

CFTR-

+ AUGAAAGCCUUUUUUCUCUUCACA 24

lntron2-1645 16745

CFTR-

+ CACAU U U AG CCAAGG ACA 18

lntron2-1646 16746

CFTR-

+ UCACAUUUAGCCAAGGACA 19

lntron2-1647 16747

CFTR-

+ UUCACAUUUAGCCAAGGACA 20

lntron2-1648 16748

CFTR-

+ UUUCACAUUUAGCCAAGGACA 21

lntron2-1649 16749

CFTR-

+ U U U U CACAU U U AGCCAAGG ACA 22

Intron2-1650 16750

CFTR-

+ U U U U U CACAU U U AGCCAAGG ACA 23

lntron2-1651 16751

CFTR-

+ AU U U U U CACAU U U AG CCAAGG ACA 24

lntron2-1652 16752

CFTR-

+ AUCAACAUGGGGGAUACA 18

lntron2-1653 16753

CFTR-

+ AAUCAACAUGGGGGAUACA 19

lntron2-1654 16754

CFTR-

+ GAAUCAACAUGGGGGAUACA 20

lntron2-1655 16755

CFTR-

+ UGAAUCAACAUGGGGGAUACA 21

lntron2-1656 16756

CFTR-

+ UUGAAUCAACAUGGGGGAUACA 22

lntron2-1657 16757

CFTR-

+ AUUGAAUCAACAUGGGGGAUACA 23

lntron2-1658 16758

CFTR-

+ AAUUGAAUCAACAUGGGGGAUACA 24

lntron2-1659 16759

502

5535.1 CFTR-

+ GAUCAGAUGGGAAAGCCA 18

Intron2-1660 16760

CFTR-

+ GGAUCAGAUGGGAAAGCCA 19

lntron2-1661 16761

CFTR-

+ UGGAUCAGAUGGGAAAGCCA 20

lntron2-623 15723

CFTR-

+ AUGGAUCAGAUGGGAAAGCCA 21

lntron2-1662 16762

CFTR-

+ AAUGGAUCAGAUGGGAAAGCCA 22

lntron2-1663 16763

CFTR-

+ AAAUGGAUCAGAUGGGAAAGCCA 23

lntron2-1664 16764

CFTR-

+ GAAAUGGAUCAGAUGGGAAAGCCA 24

lntron2-1665 16765

CFTR-

+ CAGGAGACGAAGUUUGCA 18

lntron2-1666 16766

CFTR-

+ CCAGGAGACGAAGUUUGCA 19

lntron2-1667 16767

CFTR-

+ CCCAGGAGACGAAGUUUGCA 20

lntron2-1668 16768

CFTR-

+ ACCCAGGAGACGAAGUUUGCA 21

lntron2-1669 16769

CFTR-

+ AACCCAGG AG ACG AAG U U UG CA 22

Intron2-1670 16770

CFTR-

+ G AACCCAGG AG ACG AAG U U UG CA 23

lntron2-1671 16771

CFTR-

+ UGAACCCAGGAGACGAAGUUUGCA 24

lntron2-1672 16772

CFTR-

+ CAGGAGGCAGAGUUUGCA 18

lntron2-1673 16773

CFTR-

+ CCAGGAGGCAGAGUUUGCA 19

lntron2-1674 16774

CFTR-

+ CCCAGGAGGCAGAGUUUGCA 20

lntron2-1675 16775

CFTR-

+ ACCCAGGAGGCAGAGUUUGCA 21

lntron2-1676 16776

CFTR-

+ AACCCAGGAGGCAGAGUUUGCA 22

lntron2-1677 16777

CFTR-

+ GAACCCAGGAGGCAGAGUUUGCA 23

lntron2-1678 16778

CFTR-

+ UGAACCCAGGAGGCAGAGUUUGCA 24

lntron2-1679 16779

503

5535.1 CFTR-

+ GACUCACCUUCUCCAUCA 18

Intron2-1680 16780

CFTR-

+ AGACUCACCUUCUCCAUCA 19

lntron2-1681 16781

CFTR-

+ CAGACUCACCUUCUCCAUCA 20

lntron2-1682 16782

CFTR-

+ GCAGACUCACCUUCUCCAUCA 21

lntron2-1683 16783

CFTR-

+ AGCAGACUCACCUUCUCCAUCA 22

lntron2-1684 16784

CFTR-

+ GAGCAGACUCACCUUCUCCAUCA 23

lntron2-1685 16785

CFTR-

+ GGAGCAGACUCACCUUCUCCAUCA 24

lntron2-1686 16786

CFTR-

+ UUUCGUGGUCCUUAAAGA 18

lntron2-1687 16787

CFTR-

+ CUUUCGUGGUCCUUAAAGA 19

lntron2-1688 16788

CFTR-

+ UCUUUCGUGGUCCUUAAAGA 20

lntron2-1689 16789

CFTR-

+ UUCUUUCGUGGUCCUUAAAGA 21

Intron2-1690 16790

CFTR-

+ CUUCUUUCGUGGUCCUUAAAGA 22

lntron2-1691 16791

CFTR-

+ CCUUCUUUCGUGGUCCUUAAAGA 23

lntron2-1692 16792

CFTR-

+ UCCUUCUUUCGUGGUCCUUAAAGA 24

lntron2-1693 16793

CFTR-

+ UACCAGGCCCAGAUCAGA 18

lntron2-1694 16794

CFTR-

+ AUACCAGGCCCAGAUCAGA 19

lntron2-1695 16795

CFTR-

+ CAUACCAGGCCCAGAUCAGA 20

lntron2-275 15375

CFTR-

+ ACAUACCAGGCCCAGAUCAGA 21

lntron2-1696 16796

CFTR-

+ CACAUACCAGGCCCAGAUCAGA 22

lntron2-1697 16797

CFTR-

+ CCACAUACCAGGCCCAGAUCAGA 23

lntron2-1698 16798

CFTR-

+ ACCACAUACCAGGCCCAGAUCAGA 24

lntron2-1699 16799

504

5535.1 CFTR-

+ AAGGAGAAAUGGAUCAGA 18

Intron2-1700 16800

CFTR-

+ AAAGGAGAAAUGGAUCAGA 19

Intron2-1701 16801

CFTR-

+ CAAAGGAGAAAUGGAUCAGA 20

lntron2-276 15376

CFTR-

+ U C A A AG GAG AAA UGGAUCAGA 21

Intron2-1702 16802

CFTR-

+ AUCAAAGGAGAAAUGGAUCAGA 22

Intron2-1703 16803

CFTR-

+ CAUCAAAGGAGAAAUGGAUCAGA 23

Intron2-1704 16804

CFTR-

+ CCAUCAAAGGAGAAAUGGAUCAGA 24

Intron2-1705 16805

CFTR-

+ CAUCAUAAACAAAAGAGA 18

Intron2-1706 16806

CFTR-

+ ACAUCAUAAACAAAAGAGA 19

Intron2-1707 16807

CFTR-

+ UACAUCAUAAACAAAAGAGA 20

Intron2-1708 16808

CFTR-

+ AUACAUCAUAAACAAAAGAGA 21

Intron2-1709 16809

CFTR-

+ GAUACAUCAUAAACAAAAGAGA 22

Intron2-1710 16810

CFTR-

+ GGAUACAUCAUAAACAAAAGAGA 23

lntron2-1711 16811

CFTR-

+ GGGAUACAUCAUAAACAAAAGAGA 24

lntron2-1712 16812

CFTR-

+ UCCCAGCUACUCAGGAGA 18

lntron2-1713 16813

CFTR-

+ GUCCCAGCUACUCAGGAGA 19

lntron2-1714 16814

CFTR-

+ AGUCCCAGCUACUCAGGAGA 20

lntron2-1715 16815

CFTR-

+ UAGUCCCAGCUACUCAGGAGA 21

lntron2-1716 16816

CFTR-

+ GUAGUCCCAGCUACUCAGGAGA 22

lntron2-1717 16817

CFTR-

+ UGUAGUCCCAGCUACUCAGGAGA 23

lntron2-1718 16818

CFTR-

+ CUGUAGUCCCAGCUACUCAGGAGA 24

lntron2-1719 16819

505

5535.1 CFTR-

+ UAUGAAAGAAAAAAUAGA 18

Intron2-1720 16820

CFTR-

+ CUAUGAAAGAAAAAAUAGA 19

lntron2-1721 16821

CFTR-

+ G C U A U G A A AG A A A A A A U AG A 20

lntron2-1722 16822

CFTR-

+ AGCUAUGAAAGAAAAAAUAGA 21

lntron2-1723 16823

CFTR-

+ U AG C U A U G A A AG A A A A A A U AG A 22

lntron2-1724 16824

CFTR-

+ U U AGCUAUGAAAGAAAAAAUAGA 23

lntron2-1725 16825

CFTR-

+ GUUAGCUAUGAAAGAAAAAAUAGA 24

lntron2-1726 16826

CFTR-

+ GAUACAGUGAAAACUGGA 18

lntron2-1727 16827

CFTR-

+ GGAUACAGUGAAAACUGGA 19

lntron2-1728 16828

CFTR-

+ GGGAUACAGUGAAAACUGGA 20

lntron2-1729 16829

CFTR-

+ GGGGAUACAGUGAAAACUGGA 21

Intron2-1730 16830

CFTR-

+ GGGGGAUACAGUGAAAACUGGA 22

lntron2-1731 16831

CFTR-

+ UGGGGGAUACAGUGAAAACUGGA 23

lntron2-1732 16832

CFTR-

+ AUGGGGGAUACAGUGAAAACUGGA 24

lntron2-1733 16833

CFTR-

+ CCUAACCUUUUGAUUGGA 18

lntron2-1734 16834

CFTR-

+ UCCUAACCUUUUGAUUGGA 19

lntron2-1735 16835

CFTR-

+ AUCCUAACCUUUUGAUUGGA 20

lntron2-1736 16836

CFTR-

+ GAUCCUAACCUUUUGAUUGGA 21

lntron2-1737 16837

CFTR-

+ GGAUCCUAACCUUUUGAUUGGA 22

lntron2-1738 16838

CFTR-

+ AGGAUCCUAACCUUUUGAUUGGA 23

lntron2-1739 16839

CFTR-

+ AAGGAUCCUAACCUUUUGAUUGGA 24

Intron2-1740 16840

506

5535.1 CFTR-

+ AGAGAAUGUUAGCUAUGA 18

lntron2-1741 16841

CFTR-

+ CAGAGAAUGUUAGCUAUGA 19

lntron2-1742 16842

CFTR-

+ GCAGAGAAUGUUAGCUAUGA 20

lntron2-1743 16843

CFTR-

+ AGCAGAGAAUGUUAGCUAUGA 21

lntron2-1744 16844

CFTR-

+ GAGCAGAGAAUGUUAGCUAUGA 22

lntron2-1745 16845

CFTR-

+ AGAGCAGAGAAUGUUAGCUAUGA 23

lntron2-1746 16846

CFTR-

+ GAGAGCAGAGAAUGUUAGCUAUGA 24

lntron2-1747 16847

CFTR-

+ UCCACUCAGAGUGGCUGA 18

lntron2-1748 16848

CFTR-

+ UUCCACUCAGAGUGGCUGA 19

lntron2-1749 16849

CFTR-

+ UUUCCACUCAGAGUGGCUGA 20

Intron2-1750 16850

CFTR-

+ CUUUCCACUCAGAGUGGCUGA 21

lntron2-1751 16851

CFTR-

+ GCUUUCCACUCAGAGUGGCUGA 22

lntron2-1752 16852

CFTR-

+ UGCUUUCCACUCAGAGUGGCUGA 23

lntron2-1753 16853

CFTR-

+ AUGCUUUCCACUCAGAGUGGCUGA 24

lntron2-1754 16854

CFTR-

+ AGGAUCCUAACCUUUUGA 18

lntron2-1755 16855

CFTR-

+ AAGGAUCCUAACCUUUUGA 19

lntron2-1756 16856

CFTR-

+ AAAGGAUCCUAACCUUUUGA 20

lntron2-1757 16857

CFTR-

+ AAAAGGAUCCUAACCUUUUGA 21

lntron2-1758 16858

CFTR-

+ CAAAAGGAUCCUAACCUUUUGA 22

lntron2-1759 16859

CFTR-

+ UCAAAAGGAUCCUAACCUUUUGA 23

Intron2-1760 16860

CFTR-

+ AUCAAAAGGAUCCUAACCUUUUGA 24

lntron2-1761 16861

507

5535.1 CFTR-

+ AGAGUAAGAAGCU AAA U A 18

lntron2-1762 16862

CFTR-

+ C AG AG U A AG A AG C U AAA U A 19

lntron2-1763 16863

CFTR-

+ UCAGAGUAAGAAGCUAAAUA 20

lntron2-287 15387

CFTR-

+ CUCAGAGUAAGAAGCUAAAUA 21

lntron2-1764 16864

CFTR-

+ ACUCAGAGUAAGAAGCU AAA U A 22

lntron2-1765 16865

CFTR-

+ UACUCAGAGUAAGAAGCUAAAUA 23

lntron2-1766 16866

CFTR-

+ UUACUCAGAGUAAGAAGCUAAAUA 24

lntron2-1767 16867

CFTR-

+ AAACAAACAAAAAACAUA 18

lntron2-1768 16868

CFTR-

+ CAAACAAACAAAAAACAUA 19

lntron2-1769 16869

CFTR-

+ ACAAACAAACAAAAAACAUA 20

Intron2-1770 16870

CFTR-

+ CACAAACAAACAAAAAACAUA 21

lntron2-1771 16871

CFTR-

+ ACACAAACAAACAAAAAACAUA 22

lntron2-1772 16872

CFTR-

+ AACACAAACAAACAAAAAACAUA 23

lntron2-1773 16873

CFTR-

+ CAACACAAACAAACAAAAAACAUA 24

lntron2-1774 16874

CFTR-

+ GUUUUCUUUUAAAUACUA 18

lntron2-1775 16875

CFTR-

+ UGUUUUCUUUUAAAUACUA 19

lntron2-1776 16876

CFTR-

+ CUGUUUUCUUUUAAAUACUA 20

lntron2-1777 16877

CFTR-

+ UCUGUUUUCUUUUAAAUACUA 21

lntron2-1778 16878

CFTR-

+ UUCUGUUUUCUUUUAAAUACUA 22

lntron2-1779 16879

CFTR-

+ UUUCUGUUUUCUUUUAAAUACUA 23

Intron2-1780 16880

CFTR-

+ CUUUCUGUUUUCUUUUAAAUACUA 24

lntron2-1781 16881

508

5535.1 CFTR-

+ GGGGGACUACCAUUCCUA 18

lntron2-1782 16882

CFTR-

+ GGGGGGACUACCAUUCCUA 19

lntron2-1783 16883

CFTR-

+ GGGGGGGACUACCAUUCCUA 20

lntron2-1784 16884

CFTR-

+ UGGGGGGGACUACCAUUCCUA 21

lntron2-1785 16885

CFTR-

+ AUGGGGGGGACUACCAUUCCUA 22

lntron2-1786 16886

CFTR-

+ UAUGGGGGGGACUACCAUUCCUA 23

lntron2-1787 16887

CFTR-

+ UUAUGGGGGGGACUACCAUUCCUA 24

lntron2-1788 16888

CFTR-

+ UCCCCUAGAAGCUUGCUA 18

lntron2-1789 16889

CFTR-

+ AUCCCCUAGAAGCUUGCUA 19

Intron2-1790 16890

CFTR-

+ CAUCCCCUAGAAGCUUGCUA 20

lntron2-1791 16891

CFTR-

+ GCAUCCCCUAGAAGCUUGCUA 21

lntron2-1792 16892

CFTR-

+ GGCAUCCCCUAGAAGCUUGCUA 22

lntron2-1793 16893

CFTR-

+ UGGCAUCCCCUAGAAGCUUGCUA 23

lntron2-1794 16894

CFTR-

+ UUGGCAUCCCCUAGAAGCUUGCUA 24

lntron2-1795 16895

CFTR-

+ UGGCUCUAAAUCACUCUA 18

lntron2-1796 16896

CFTR-

+ AUGGCUCUAAAUCACUCUA 19

lntron2-1797 16897

CFTR-

+ CAUGGCUCUAAAUCACUCUA 20

lntron2-1798 16898

CFTR-

+ ACAUGGCUCUAAAUCACUCUA 21

lntron2-1799 16899

CFTR-

+ AACAUGGCUCUAAAUCACUCUA 22

Intron2-1800 16900

CFTR-

+ AAACAUGGCUCUAAAUCACUCUA 23

Intron2-1801 16901

CFTR-

+ UAAACAUGGCUCUAAAUCACUCUA 24

Intron2-1802 16902

509

5535.1 CFTR-

+ GUAAAUGAAAGUGAAGUA 18

Intron2-1803 16903

CFTR-

+ UGUAAAUGAAAGUGAAGUA 19

Intron2-1804 16904

CFTR-

+ AUGUAAAUGAAAGUGAAGUA 20

Intron2-1805 16905

CFTR-

+ GAUGUAAAUGAAAGUGAAGUA 21

Intron2-1806 16906

CFTR-

+ AGAUGUAAAUGAAAGUGAAGUA 22

Intron2-1807 16907

CFTR-

+ GAGAUGUAAAUGAAAGUGAAGUA 23

Intron2-1808 16908

CFTR-

+ UGAGAUGUAAAUGAAAGUGAAGUA 24

Intron2-1809 16909

CFTR-

+ CUUAAUUUUCAAACUGUA 18

Intron2-1810 16910

CFTR-

+ UCUUAAUUUUCAAACUGUA 19

lntron2-1811 16911

CFTR-

+ AUCUUAAUUUUCAAACUGUA 20

lntron2-1812 16912

CFTR-

+ CAUCUUAAUUUUCAAACUGUA 21

lntron2-1813 16913

CFTR-

+ UCAUCUUAAUUUUCAAACUGUA 22

lntron2-1814 16914

CFTR-

+ AUCAUCUUAAUUUUCAAACUGUA 23

lntron2-1815 16915

CFTR-

+ UAUCAUCUUAAUUUUCAAACUGUA 24

lntron2-1816 16916

CFTR-

+ UGCCACUGAUUUCUGUUA 18

lntron2-1817 16917

CFTR-

+ UUGCCACUGAUUUCUGUUA 19

lntron2-1818 16918

CFTR-

+ AUUGCCACUGAUUUCUGUUA 20

lntron2-1819 16919

CFTR-

+ UAUUGCCACUGAUUUCUGUUA 21

Intron2-1820 16920

CFTR-

+ UUAUUGCCACUGAUUUCUGUUA 22

lntron2-1821 16921

CFTR-

+ GUUAUUGCCACUGAUUUCUGUUA 23

lntron2-1822 16922

CFTR-

+ AGUUAUUGCCACUGAUUUCUGUUA 24

lntron2-1823 16923

510

5535.1 CFTR-

+ AAACUGAGAGAUUCUUUA 18

lntron2-1824 16924

CFTR-

+ GAAACUGAGAGAUUCUUUA 19

lntron2-1825 16925

CFTR-

+ GGAAACUGAGAGAUUCUUUA 20

lntron2-57 15157

CFTR-

+ AGGAAACUGAGAGAUUCUUUA 21

lntron2-1826 16926

CFTR-

+ AAGGAAACUGAGAGAUUCUUUA 22

lntron2-1827 16927

CFTR-

+ AAAGGAAACUGAGAGAUUCUUUA 23

lntron2-1828 16928

CFTR-

+ G AAAGG AAACUG AG AG AU U CU U U A 24

lntron2-1829 16929

CFTR-

+ GGGGGAUACAGUGAAAAC 18

Intron2-1830 16930

CFTR-

+ UGGGGGAUACAGUGAAAAC 19

lntron2-1831 16931

CFTR-

+ AUGGGGGAUACAGUGAAAAC 20

lntron2-297 15397

CFTR-

+ CAUGGGGGAUACAGUGAAAAC 21

lntron2-1832 16932

CFTR-

+ ACAUGGGGGAUACAGUGAAAAC 22

lntron2-1833 16933

CFTR-

+ AACAUGGGGGAUACAGUGAAAAC 23

lntron2-1834 16934

CFTR-

+ CAACAUGGGGGAUACAGUGAAAAC 24

lntron2-1835 16935

CFTR-

+ UUCUUUAAUGGGUGAAAC 18

lntron2-1836 16936

CFTR-

+ UUUCUUUAAUGGGUGAAAC 19

lntron2-1837 16937

CFTR-

+ AUUUCUUUAAUGGGUGAAAC 20

lntron2-1838 16938

CFTR-

+ AAUUUCUUUAAUGGGUGAAAC 21

lntron2-1839 16939

CFTR-

+ GAAUUUCUUUAAUGGGUGAAAC 22

Intron2-1840 16940

CFTR-

+ GGAAUUUCUUUAAUGGGUGAAAC 23

lntron2-1841 16941

CFTR-

+ GGGAAUUUCUUUAAUGGGUGAAAC 24

lntron2-1842 16942

511

5535.1 CFTR-

+ U U U U U AAAU UG AAU CAAC 18

lntron2-1843 16943

CFTR-

+ U U U U U U AAAU UG AAU CAAC 19

lntron2-1844 16944

CFTR-

+ AU U U U U U AAAU UG AAU CAAC 20

lntron2-1845 16945

CFTR-

+ UAUUUUUUAAAUUGAAUCAAC 21

lntron2-1846 16946

CFTR-

+ AUAUUUUUUAAAUUGAAUCAAC 22

lntron2-1847 16947

CFTR-

+ UAUAUUUUU U AAAU UG AAU CAAC 23

lntron2-1848 16948

CFTR-

+ GUAUAUUUUUUAAAUUGAAUCAAC 24

lntron2-1849 16949

CFTR-

+ G G AG C A A AG AGUUCUAAC 18

Intron2-1850 16950

CFTR-

+ AGG AGCAAAG AG U U CU AAC 19

lntron2-1851 16951

CFTR-

+ UAGGAGCAAAGAGUUCUAAC 20

lntron2-1852 16952

CFTR-

+ AUAGGAGCAAAGAGUUCUAAC 21

lntron2-1853 16953

CFTR-

+ GAUAGGAGCAAAGAGUUCUAAC 22

lntron2-1854 16954

CFTR-

+ AG AU AGG AGCAAAG AG U U CU AAC 23

lntron2-1855 16955

CFTR-

+ AAGAUAGGAGCAAAGAGUUCUAAC 24

lntron2-1856 16956

CFTR-

+ CAACCAUCUGGCAACCAC 18

lntron2-1857 16957

CFTR-

+ UCAACCAUCUGGCAACCAC 19

lntron2-1858 16958

CFTR-

+ UUCAACCAUCUGGCAACCAC 20

lntron2-1859 16959

CFTR-

+ CU UCAACCAUCUGGCAACCAC 21

Intron2-1860 16960

CFTR-

+ UCU UCAACCAUCUGGCAACCAC 22

lntron2-1861 16961

CFTR-

+ UUCUUCAACCAUCUGGCAACCAC 23

lntron2-1862 16962

CFTR-

+ GUUCUUCAACCAUCUGGCAACCAC 24

lntron2-1863 16963

512

5535.1 CFTR-

+ AAAAAU U U CAUG AACCAC 18

lntron2-1864 16964

CFTR-

+ GAAAAAU U U CAUG AACCAC 19

lntron2-1865 16965

CFTR-

+ UGAAAAAUUUCAUGAACCAC 20

lntron2-1866 16966

CFTR-

+ AUGAAAAAUUUCAUGAACCAC 21

lntron2-1867 16967

CFTR-

+ GAUGAAAAAUUUCAUGAACCAC 22

lntron2-1868 16968

CFTR-

+ AGAUGAAAAAUUUCAUGAACCAC 23

lntron2-1869 16969

CFTR-

+ GAGAUGAAAAAUUUCAUGAACCAC 24

Intron2-1870 16970

CFTR-

+ UGUGAAAAAGUGGUCCAC 18

lntron2-1871 16971

CFTR-

+ AUGUGAAAAAGUGGUCCAC 19

lntron2-1872 16972

CFTR-

+ AAUGUGAAAAAGUGGUCCAC 20

lntron2-1873 16973

CFTR-

+ CAAUGUGAAAAAGUGGUCCAC 21

lntron2-1874 16974

CFTR-

+ UCAAUGUGAAAAAGUGGUCCAC 22

lntron2-1875 16975

CFTR-

+ UUCAAUGUGAAAAAGUGGUCCAC 23

lntron2-1876 16976

CFTR-

+ GUUCAAUGUGAAAAAGUGGUCCAC 24

lntron2-1877 16977

CFTR-

+ AGGCCCUAUUCUAGGCAC 18

lntron2-1878 16978

CFTR-

+ CAGGCCCUAUUCUAGGCAC 19

lntron2-1879 16979

CFTR-

+ CCAGGCCCUAUUCUAGGCAC 20

Intron2-1880 16980

CFTR-

+ GCCAGGCCCUAUUCUAGGCAC 21

lntron2-1881 16981

CFTR-

+ UGCCAGGCCCUAUUCUAGGCAC 22

lntron2-1882 16982

CFTR-

+ AUGCCAGGCCCUAUUCUAGGCAC 23

lntron2-1883 16983

CFTR-

+ UAUGCCAGGCCCUAUUCUAGGCAC 24

lntron2-1884 16984

513

5535.1 CFTR-

+ CUGAGGCAGGAGAAUCAC 18

lntron2-1885 16985

CFTR-

+ GCUGAGGCAGGAGAAUCAC 19

lntron2-1886 16986

CFTR-

+ GGCUGAGGCAGGAGAAUCAC 20

lntron2-1887 16987

CFTR-

+ AGGCUGAGGCAGGAGAAUCAC 21

lntron2-1888 16988

CFTR-

+ GAGGCUGAGGCAGGAGAAUCAC 22

lntron2-1889 16989

CFTR-

+ AGAGGCUGAGGCAGGAGAAUCAC 23

Intron2-1890 16990

CFTR-

+ GAGAGGCUGAGGCAGGAGAAUCAC 24

lntron2-1891 16991

CFTR-

+ CCAAGGCGGGCAGAUCAC 18

lntron2-1892 16992

CFTR-

+ GCCAAGGCGGGCAGAUCAC 19

lntron2-1893 16993

CFTR-

+ GGCCAAGGCGGGCAGAUCAC 20

lntron2-1894 16994

CFTR-

+ AGGCCAAGGCGGGCAGAUCAC 21

lntron2-1895 16995

CFTR-

+ GAGGCCAAGGCGGGCAGAUCAC 22

lntron2-1896 16996

CFTR-

+ GGAGGCCAAGGCGGGCAGAUCAC 23

lntron2-1897 16997

CFTR-

+ GGGAGGCCAAGGCGGGCAGAUCAC 24

lntron2-1898 16998

CFTR-

+ CCAAGGUGGGCAGAUCAC 18

lntron2-1899 16999

CFTR-

+ GCCAAGGUGGGCAGAUCAC 19

Intron2-1900 17000

CFTR-

+ GGCCAAGGUGGGCAGAUCAC 20

Intron2-1901 17001

CFTR-

+ AGGCCAAGGUGGGCAGAUCAC 21

Intron2-1902 17002

CFTR-

+ GAGGCCAAGGUGGGCAGAUCAC 22

Intron2-1903 17003

CFTR-

+ GGAGGCCAAGGUGGGCAGAUCAC 23

Intron2-1904 17004

CFTR-

+ GGGAGGCCAAGGUGGGCAGAUCAC 24

Intron2-1905 17005

514

5535.1 CFTR-

+ AAAGUGAAG U AG AG AG AC 18

Intron2-1906 17006

CFTR-

+ GAAAGUGAAG U AG AG AG AC 19

Intron2-1907 17007

CFTR-

+ U GAAAGUGAAG U AG AG AG AC 20

Intron2-1908 17008

CFTR-

+ AUGAAAGUGAAGUAGAGAGAC 21

Intron2-1909 17009

CFTR-

+ AAUGAAAGUGAAGUAGAGAGAC 22

Intron2-1910 17010

CFTR-

+ AAA U G A A AG UGAAGUAGAGAGAC 23

lntron2-1911 17011

CFTR-

+ UAAAUGAAAGUGAAGUAGAGAGAC 24

lntron2-1912 17012

CFTR-

+ GCCUGUAAACCCAGCUAC 18

lntron2-1913 17013

CFTR-

+ UGCCUGUAAACCCAGCUAC 19

lntron2-1914 17014

CFTR-

+ GUGCCUGUAAACCCAGCUAC 20

lntron2-1915 17015

CFTR-

+ AGUGCCUGUAAACCCAGCUAC 21

lntron2-1916 17016

CFTR-

+ GAGUGCCUGUAAACCCAGCUAC 22

lntron2-1917 17017

CFTR-

+ CGAGUGCCUGUAAACCCAGCUAC 23

lntron2-1918 17018

CFTR-

+ GCGAGUGCCUGUAAACCCAGCUAC 24

lntron2-1919 17019

CFTR-

+ AUAGAAUGGGGUAGUUAC 18

Intron2-1920 17020

CFTR-

+ AAUAGAAUGGGGUAGUUAC 19

lntron2-1921 17021

CFTR-

+ AAAUAGAAUGGGGUAGUUAC 20

lntron2-1922 17022

CFTR-

+ AAAAUAGAAUGGGGUAGUUAC 21

lntron2-1923 17023

CFTR-

+ AAAAAUAGAAUGGGGUAGUUAC 22

lntron2-1924 17024

CFTR-

+ AAAAAAUAGAAUGGGGUAGUUAC 23

lntron2-1925 17025

CFTR-

+ GAAAAAAUAGAAUGGGGUAGUUAC 24

lntron2-1926 17026

515

5535.1 CFTR-

+ AGGAGAAUCACUUGAACC 18

lntron2-1927 17027

CFTR-

+ CAGGAGAAUCACUUGAACC 19

lntron2-1928 17028

CFTR-

+ GCAGGAGAAUCACUUGAACC 20

lntron2-1929 17029

CFTR-

+ GGCAGGAGAAUCACUUGAACC 21

Intron2-1930 17030

CFTR-

+ AGGCAGGAGAAUCACUUGAACC 22

lntron2-1931 17031

CFTR-

+ GAGGCAGGAGAAUCACUUGAACC 23

lntron2-1932 17032

CFTR-

+ UGAGGCAGGAGAAUCACUUGAACC 24

lntron2-1933 17033

CFTR-

+ CUGAGAUUCGCUUGAACC 18

lntron2-1934 17034

CFTR-

+ ACUGAGAUUCGCUUGAACC 19

lntron2-1935 17035

CFTR-

+ GACUGAGAUUCGCUUGAACC 20

lntron2-1936 17036

CFTR-

+ AGACUGAGAUUCGCUUGAACC 21

lntron2-1937 17037

CFTR-

+ GAGACUGAGAUUCGCUUGAACC 22

lntron2-1938 17038

CFTR-

+ GGAGACUGAGAUUCGCUUGAACC 23

lntron2-1939 17039

CFTR-

+ AGGAGACUGAGAUUCGCUUGAACC 24

Intron2-1940 17040

CFTR-

+ GAG C A A AG AGUUCUAACC 18

lntron2-1941 17041

CFTR-

+ GGAGCAAAGAGUUCUAACC 19

lntron2-1942 17042

CFTR-

+ AGGAGCAAAGAGUUCUAACC 20

Intron2-305 15405

CFTR-

+ UAGGAGCAAAGAGUUCUAACC 21

lntron2-1943 17043

CFTR-

+ AUAGGAGCAAAGAGUUCUAACC 22

lntron2-1944 17044

CFTR-

+ GAUAGGAGCAAAGAGUUCUAACC 23

lntron2-1945 17045

CFTR-

+ AGAUAGGAGCAAAGAGUUCUAACC 24

lntron2-1946 17046

516

5535.1 CFTR-

+ AAGUGAAGUAGAGAGACC 18

lntron2-1947 17047

CFTR-

+ AAAGUGAAGUAGAGAGACC 19

lntron2-1948 17048

CFTR-

+ GAAAGUGAAGUAGAGAGACC 20

Intron2-60 15160

CFTR-

+ UGAAAGUGAAGUAGAGAGACC 21

lntron2-1949 17049

CFTR-

+ AUGAAAGUGAAGUAGAGAGACC 22

Intron2-1950 17050

CFTR-

+ AAUGAAAGUGAAGUAGAGAGACC 23

lntron2-1951 17051

CFTR-

+ AAAUGAAAGUGAAGUAGAGAGACC 24

lntron2-1952 17052

CFTR-

+ AAGAGGUCUCUAGUGACC 18

lntron2-1953 17053

CFTR-

+ UAAGAGGUCUCUAGUGACC 19

lntron2-1954 17054

CFTR-

+ AUAAGAGGUCUCUAGUGACC 20

lntron2-1955 17055

CFTR-

+ CAU AAGAGGUCUCUAGUGACC 21

lntron2-1956 17056

CFTR-

+ UCAUAAGAGGUCUCUAGUGACC 22

lntron2-1957 17057

CFTR-

+ UUCAUAAGAGGUCUCUAGUGACC 23

lntron2-1958 17058

CFTR-

+ UUUCAUAAGAGGUCUCUAGUGACC 24

lntron2-1959 17059

CFTR-

+ GGAGAAUCACUUGAACCC 18

Intron2-1960 17060

CFTR-

+ AGGAGAAUCACUUGAACCC 19

lntron2-1961 17061

CFTR-

+ CAGGAGAAUCACUUGAACCC 20

lntron2-636 15736

CFTR-

+ GCAGGAGAAUCACUUGAACCC 21

lntron2-1962 17062

CFTR-

+ GGCAGGAGAAUCACUUGAACCC 22

lntron2-1963 17063

CFTR-

+ AGGCAGGAGAAUCACUUGAACCC 23

lntron2-1964 17064

CFTR-

+ GAGGCAGGAGAAUCACUUGAACCC 24

lntron2-1965 17065

517

5535.1 CFTR-

+ UGAGAUUCGCUUGAACCC 18

lntron2-1966 17066

CFTR-

+ CUGAGAUUCGCUUGAACCC 19

lntron2-1967 17067

CFTR-

+ ACUGAGAUUCGCUUGAACCC 20

lntron2-637 15737

CFTR-

+ GACUGAGAUUCGCUUGAACCC 21

lntron2-1968 17068

CFTR-

+ AGACUGAGAUUCGCUUGAACCC 22

lntron2-1969 17069

CFTR-

+ GAGACUGAGAUUCGCUUGAACCC 23

Intron2-1970 17070

CFTR-

+ GGAGACUGAGAUUCGCUUGAACCC 24

lntron2-1971 17071

CFTR-

+ AUGGAUCUUGGCAUCCCC 18

lntron2-1972 17072

CFTR-

+ CAUGGAUCUUGGCAUCCCC 19

lntron2-1973 17073

CFTR-

+ GCAUGGAUCUUGGCAUCCCC 20

lntron2-1974 17074

CFTR-

+ AGCAUGGAUCUUGGCAUCCCC 21

lntron2-1975 17075

CFTR-

+ AAGCAUGGAUCUUGGCAUCCCC 22

lntron2-1976 17076

CFTR-

+ UAAGCAUGGAUCUUGGCAUCCCC 23

lntron2-1977 17077

CFTR-

+ CUAAGCAUGGAUCUUGGCAUCCCC 24

lntron2-1978 17078

CFTR-

+ CUAGACUAUGAGUGGCCC 18

lntron2-1979 17079

CFTR-

+ UCUAGACUAUGAGUGGCCC 19

Intron2-1980 17080

CFTR-

+ UUCUAGACUAUGAGUGGCCC 20

lntron2-1981 17081

CFTR-

+ AUUCUAGACUAUGAGUGGCCC 21

lntron2-1982 17082

CFTR-

+ CAUUCUAGACUAUGAGUGGCCC 22

lntron2-1983 17083

CFTR-

+ UCAUUCUAGACUAUGAGUGGCCC 23

lntron2-1984 17084

CFTR-

+ UUCAUUCUAGACUAUGAGUGGCCC 24

lntron2-1985 17085

518

5535.1 CFTR-

+ AUUACCUUAAGACUUCCC 18

lntron2-1986 17086

CFTR-

+ CAUUACCUUAAGACUUCCC 19

lntron2-1987 17087

CFTR-

+ CCAUUACCUUAAGACUUCCC 20

lntron2-314 15414

CFTR-

+ GCCAUUACCUUAAGACUUCCC 21

lntron2-1988 17088

CFTR-

+ AGCCAUUACCUUAAGACUUCCC 22

lntron2-1989 17089

CFTR-

+ UAGCCAUUACCUUAAGACUUCCC 23

Intron2-1990 17090

CFTR-

+ GUAGCCAUUACCUUAAGACUUCCC 24

lntron2-1991 17091

CFTR-

+ GGAUCAGAUGGGAAAGCC 18

lntron2-1992 17092

CFTR-

+ UGGAUCAGAUGGGAAAGCC 19

lntron2-1993 17093

CFTR-

+ AUGGAUCAGAUGGGAAAGCC 20

lntron2-1994 17094

CFTR-

+ AAUGGAUCAGAUGGGAAAGCC 21

lntron2-1995 17095

CFTR-

+ AAAUGGAUCAGAUGGGAAAGCC 22

lntron2-1996 17096

CFTR-

+ GAAAUGGAUCAGAUGGGAAAGCC 23

lntron2-1997 17097

CFTR-

+ AGAAAUGGAUCAGAUGGGAAAGCC 24

lntron2-1998 17098

CFTR-

+ GAUUUUUCACAUUUAGCC 18

lntron2-1999 17099

CFTR-

+ GGAUUUUUCACAUUUAGCC 19

Intron2-2000 17100

CFTR-

+ GGGAUUUUUCACAUUUAGCC 20

Intron2-2001 17101

CFTR-

+ UGGGAUUUUUCACAUUUAGCC 21

Intron2-2002 17102

CFTR-

+ CUGGGAUUUUUCACAUUUAGCC 22

Intron2-2003 17103

CFTR-

+ UCUGGGAUUUUUCACAUUUAGCC 23

Intron2-2004 17104

CFTR-

+ CUCUGGGAUUUUUCACAUUUAGCC 24

Intron2-2005 17105

519

5535.1 CFTR-

+ GGGGGGGACUACCAUUCC 18

Intron2-2006 17106

CFTR-

+ UGGGGGGGACUACCAUUCC 19

Intron2-2007 17107

CFTR-

+ AUGGGGGGGACUACCAUUCC 20

Intron2-2008 17108

CFTR-

+ UAUGGGGGGGACUACCAUUCC 21

Intron2-2009 17109

CFTR-

+ UUAUGGGGGGGACUACCAUUCC 22

Intron2-2010 17110

CFTR-

+ UUUAUGGGGGGGACUACCAUUCC 23

Intron2-2011 17111

CFTR-

+ CUUUAUGGGGGGGACUACCAUUCC 24

Intron2-2012 17112

CFTR-

+ CAUUACCUUAAGACUUCC 18

Intron2-2013 17113

CFTR-

+ CCAUUACCUUAAGACUUCC 19

Intron2-2014 17114

CFTR-

+ GCCAU UACCUUAAGACUUCC 20

Intron2-2015 17115

CFTR-

+ AGCCAUUACCUUAAGACUUCC 21

Intron2-2016 17116

CFTR-

+ UAGCCAUUACCUUAAGACUUCC 22

Intron2-2017 17117

CFTR-

+ GUAGCCAUUACCUUAAGACUUCC 23

Intron2-2018 17118

CFTR-

+ AGUAGCCAUUACCUUAAGACUUCC 24

Intron2-2019 17119

CFTR-

+ GCACCAUUACACUCCAGC 18

Intron2-2020 17120

CFTR-

+ UGCACCAUUACACUCCAGC 19

Intron2-2021 17121

CFTR-

+ UUGCACCAUUACACUCCAGC 20

Intron2-2022 17122

CFTR-

+ AUUGCACCAUUACACUCCAGC 21

Intron2-2023 17123

CFTR-

+ AAUUGCACCAUUACACUCCAGC 22

Intron2-2024 17124

CFTR-

+ AAAUUGCACCAUUACACUCCAGC 23

Intron2-2025 17125

CFTR-

+ AAAAUUGCACCAUUACACUCCAGC 24

Intron2-2026 17126

520

5535.1 CFTR-

+ CAGGAGACUGAGAUUCGC 18

Intron2-2027 17127

CFTR-

+ UCAGGAGACUGAGAUUCGC 19

Intron2-2028 17128

CFTR-

+ CUCAGGAGACUGAGAUUCGC 20

Intron2-2029 17129

CFTR-

+ ACUCAGGAGACUGAGAUUCGC 21

Intron2-2030 17130

CFTR-

+ UACUCAGGAGACUGAGAUUCGC 22

Intron2-2031 17131

CFTR-

+ CUACUCAGGAGACUGAGAUUCGC 23

Intron2-2032 17132

CFTR-

+ GCUACUCAGGAGACUGAGAUUCGC 24

Intron2-2033 17133

CFTR-

+ UACUCGAGAGGCUGAGGC 18

Intron2-2034 17134

CFTR-

+ CUACUCGAGAGGCUGAGGC 19

Intron2-2035 17135

CFTR-

+ GCUACUCGAGAGGCUGAGGC 20

lntron2-461 15561

CFTR-

+ AGCUACUCGAGAGGCUGAGGC 21

Intron2-2036 17136

CFTR-

+ CAGCUACUCGAGAGGCUGAGGC 22

Intron2-2037 17137

CFTR-

+ CCAGCUACUCGAGAGGCUGAGGC 23

Intron2-2038 17138

CFTR-

+ CCCAGCUACUCGAGAGGCUGAGGC 24

Intron2-2039 17139

CFTR-

+ U CU AAAGG AG U AAU AGG C 18

Intron2-2040 17140

CFTR-

+ CUCUAAAGGAGUAAUAGGC 19

Intron2-2041 17141

CFTR-

+ ACUCUAAAGGAGUAAUAGGC 20

lntron2-662 15762

CFTR-

+ CACUCUAAAGGAGUAAUAGGC 21

Intron2-2042 17142

CFTR-

+ UCACUCUAAAGGAGUAAUAGGC 22

Intron2-2043 17143

CFTR-

+ AUCACUCUAAAGGAGUAAUAGGC 23

Intron2-2044 17144

CFTR-

+ AAUCACUCUAAAGGAGUAAUAGGC 24

Intron2-2045 17145

521

5535.1 CFTR-

+ CAGGCCUGUGCUGUUGGC 18

Intron2-2046 17146

CFTR-

+ UCAGGCCUGUGCUGUUGGC 19

Intron2-2047 17147

CFTR-

+ AUCAGGCCUGUGCUGUUGGC 20

Intron2-2048 17148

CFTR-

+ CAUCAGGCCUGUGCUGUUGGC 21

Intron2-2049 17149

CFTR-

+ GCAUCAGGCCUGUGCUGUUGGC 22

Intron2-2050 17150

CFTR-

+ GGCAUCAGGCCUGUGCUGUUGGC 23

Intron2-2051 17151

CFTR-

+ UGGCAUCAGGCCUGUGCUGUUGGC 24

Intron2-2052 17152

CFTR-

+ CAUAUCCUGACUACAAUC 18

Intron2-2053 17153

CFTR-

+ UCAUAUCCUGACUACAAUC 19

Intron2-2054 17154

CFTR-

+ UUCAUAUCCUGACUACAAUC 20

Intron2-2055 17155

CFTR-

+ GUUCAUAUCCUGACUACAAUC 21

Intron2-2056 17156

CFTR-

+ AGUUCAUAUCCUGACUACAAUC 22

Intron2-2057 17157

CFTR-

+ AAGUUCAUAUCCUGACUACAAUC 23

Intron2-2058 17158

CFTR-

+ AAAGUUCAUAUCCUGACUACAAUC 24

Intron2-2059 17159

CFTR-

+ CUGUAAACCCAGCUACUC 18

Intron2-2060 17160

CFTR-

+ CCUGUAAACCCAGCUACUC 19

Intron2-2061 17161

CFTR-

+ GCCUGUAAACCCAGCUACUC 20

Intron2-2062 17162

CFTR-

+ UGCCUGUAAACCCAGCUACUC 21

Intron2-2063 17163

CFTR-

+ GUGCCUGUAAACCCAGCUACUC 22

Intron2-2064 17164

CFTR-

+ AGUGCCUGUAAACCCAGCUACUC 23

Intron2-2065 17165

CFTR-

+ GAGUGCCUGUAAACCCAGCUACUC 24

Intron2-2066 17166

522

5535.1 CFTR-

+ CUGUAGUCCCAGCUACUC 18

Intron2-2067 17167

CFTR-

+ CCUGUAGUCCCAGCUACUC 19

Intron2-2068 17168

CFTR-

+ GCCUGUAGUCCCAGCUACUC 20

lntron2-463 15563

CFTR-

+ UGCCUGUAGUCCCAGCUACUC 21

Intron2-2069 17169

CFTR-

+ AUGCCUGUAGUCCCAGCUACUC 22

Intron2-2070 17170

CFTR-

+ CAUGCCUGUAGUCCCAGCUACUC 23

Intron2-2071 17171

CFTR-

+ GCAUGCCUGUAGUCCCAGCUACUC 24

Intron2-2072 17172

CFTR-

+ UGAGGAGAAGGCAAGGUC 18

Intron2-2073 17173

CFTR-

+ CUGAGGAGAAGGCAAGGUC 19

Intron2-2074 17174

CFTR-

+ CCUGAGGAGAAGGCAAGGUC 20

lntron2-333 15433

CFTR-

+ ACCUGAGGAGAAGGCAAGGUC 21

Intron2-2075 17175

CFTR-

+ UACCUGAGGAGAAGGCAAGGUC 22

Intron2-2076 17176

CFTR-

+ UUACCUGAGGAGAAGGCAAGGUC 23

Intron2-2077 17177

CFTR-

+ GUUACCUGAGGAGAAGGCAAGGUC 24

Intron2-2078 17178

CFTR-

+ UGGUGGAAACCAUACUUC 18

Intron2-2079 17179

CFTR-

+ AUGGUGGAAACCAUACUUC 19

Intron2-2080 17180

CFTR-

+ CAUGGUGGAAACCAUACUUC 20

lntron2-669 15769

CFTR-

+ ACAUGGUGGAAACCAUACUUC 21

Intron2-2081 17181

CFTR-

+ AACAUGGUGGAAACCAUACUUC 22

Intron2-2082 17182

CFTR-

+ GAACAUGGUGGAAACCAUACUUC 23

Intron2-2083 17183

CFTR-

+ GGAACAUGGUGGAAACCAUACUUC 24

Intron2-2084 17184

523

5535.1 CFTR-

+ UCACAUAGUUCAGGCUUC 18

Intron2-2085 17185

CFTR-

+ UUCACAUAGUUCAGGCUUC 19

Intron2-2086 17186

CFTR-

+ CUUCACAUAGUUCAGGCUUC 20

Intron2-2087 17187

CFTR-

+ UCUUCACAUAGUUCAGGCUUC 21

Intron2-2088 17188

CFTR-

+ GUCUUCACAUAGUUCAGGCUUC 22

Intron2-2089 17189

CFTR-

+ GGUCUUCACAUAGUUCAGGCUUC 23

Intron2-2090 17190

CFTR-

+ AGGUCUUCACAUAGUUCAGGCUUC 24

Intron2-2091 17191

CFTR-

+ ACAG AG AUG AAAAAU U U C 18

Intron2-2092 17192

CFTR-

+ U ACAG AG AUG AAAAAU U U C 19

Intron2-2093 17193

CFTR-

+ GUACAGAGAUGAAAAAUUUC 20

Intron2-2094 17194

CFTR-

+ UGUACAGAGAUGAAAAAUUUC 21

Intron2-2095 17195

CFTR-

+ CUGUACAGAGAUGAAAAAUUUC 22

Intron2-2096 17196

CFTR-

+ ACUG U ACAG AG AUG AAAAAU U U C 23

Intron2-2097 17197

CFTR-

+ AACUGUACAGAGAUGAAAAAUUUC 24

Intron2-2098 17198

CFTR-

+ ACCAAAUGUGUAUUUUUC 18

Intron2-2099 17199

CFTR-

+ AACCAAAUGUGUAUUUUUC 19

Intron2-2100 17200

CFTR-

+ AAACCAAAUGUGUAUUUUUC 20

Intron2-670 15770

CFTR-

+ GAAACCAAAUGUGUAUUUUUC 21

Intron2-2101 17201

CFTR-

+ UGAAACCAAAUGUGUAUUUUUC 22

Intron2-2102 17202

CFTR-

+ CUGAAACCAAAUGUGUAUUUUUC 23

Intron2-2103 17203

CFTR-

+ UCUGAAACCAAAUGUGUAUUUUUC 24

Intron2-2104 17204

524

5535.1 CFTR-

+ UCACCUUCUCCAUCAAAG 18

Intron2-2105 17205

CFTR-

+ CUCACCUUCUCCAUCAAAG 19

Intron2-2106 17206

CFTR-

+ ACUCACCUUCUCCAUCAAAG 20

Intron2-2107 17207

CFTR-

+ GACUCACCUUCUCCAUCAAAG 21

Intron2-2108 17208

CFTR-

+ AGACUCACCUUCUCCAUCAAAG 22

Intron2-2109 17209

CFTR-

+ CAGACUCACCUUCUCCAUCAAAG 23

Intron2-2110 17210

CFTR-

+ GCAGACUCACCUUCUCCAUCAAAG 24

lntron2-2111 17211

CFTR-

+ AAACU U AG AU AU U CAAAG 18

lntron2-2112 17212

CFTR-

+ AAAACU U AG AU AU U CAAAG 19

lntron2-2113 17213

CFTR-

+ U AAAACU U AG AU AU U CAAAG 20

lntron2-2114 17214

CFTR-

+ U U AAAACU U AG AU AU U CAAAG 21

lntron2-2115 17215

CFTR-

+ AU U AAAACU U AG AU AU U CAAAG 22

lntron2-2116 17216

CFTR-

+ AAU U AAAACU U AG AU AU U CAAAG 23

lntron2-2117 17217

CFTR-

+ CAAU U AAAACU U AG AU AU U CAAAG 24

lntron2-2118 17218

CFTR-

+ ACACUUUGGGAGGCCAAG 18

lntron2-2119 17219

CFTR-

+ AACACUUUGGGAGGCCAAG 19

Intron2-2120 17220

CFTR-

+ CAACACUUUGGGAGGCCAAG 20

lntron2-2121 17221

CFTR-

+ CCAACACUUUGGGAGGCCAAG 21

lntron2-2122 17222

CFTR-

+ CCCAACACUUUGGGAGGCCAAG 22

lntron2-2123 17223

CFTR-

+ UCCCAACACUUUGGGAGGCCAAG 23

lntron2-2124 17224

CFTR-

+ AUCCCAACACUUUGGGAGGCCAAG 24

lntron2-2125 17225

525

5535.1 CFTR-

+ GCAUUUUGGGAGGCCAAG 18

lntron2-2126 17226

CFTR-

+ AGCAUUUUGGGAGGCCAAG 19

lntron2-2127 17227

CFTR-

+ CAG CA U U U U GG G AG G CCAAG 20

lntron2-2128 17228

CFTR-

+ CCAGCAUUUUGGGAGGCCAAG 21

lntron2-2129 17229

CFTR-

+ CCCAGCAUUUUGGGAGGCCAAG 22

Intron2-2130 17230

CFTR-

+ UCCCAGCAUUUUGGGAGGCCAAG 23

lntron2-2131 17231

CFTR-

+ AUCCCAGCAUUUUGGGAGGCCAAG 24

lntron2-2132 17232

CFTR-

+ AUGUAAAUGAAAGUGAAG 18

lntron2-2133 17233

CFTR-

+ GAUGUAAAUGAAAGUGAAG 19

lntron2-2134 17234

CFTR-

+ AGAUGUAAAUGAAAGUGAAG 20

lntron2-2135 17235

CFTR-

+ GAGAUGUAAAUGAAAGUGAAG 21

lntron2-2136 17236

CFTR-

+ UGAGAUGUAAAUGAAAGUGAAG 22

lntron2-2137 17237

CFTR-

+ CUGAGAUGUAAAUGAAAGUGAAG 23

lntron2-2138 17238

CFTR-

+ GCUGAGAUGUAAAUGAAAGUGAAG 24

lntron2-2139 17239

CFTR-

+ UAAAGGAGUAAUACACAG 18

Intron2-2140 17240

CFTR-

+ AUAAAGGAGUAAUACACAG 19

lntron2-2141 17241

CFTR-

+ CAUAAAGGAGUAAUACACAG 20

lntron2-2142 17242

CFTR-

+ ACAUAAAGGAGUAAUACACAG 21

lntron2-2143 17243

CFTR-

+ AACAUAAAGGAGUAAUACACAG 22

lntron2-2144 17244

CFTR-

+ AAACAUAAAGGAGUAAUACACAG 23

lntron2-2145 17245

CFTR-

+ AAAACAUAAAGGAGUAAUACACAG 24

lntron2-2146 17246

526

5535.1 CFTR-

+ GUGAAGUAGAGAGACCAG 18

lntron2-2147 17247

CFTR-

+ AGUGAAGUAGAGAGACCAG 19

lntron2-2148 17248

CFTR-

+ AAGUGAAG U AG AG AG ACCAG 20

lntron2-2149 17249

CFTR-

+ AAAGUGAAGUAGAGAGACCAG 21

Intron2-2150 17250

CFTR-

+ GAAAGUGAAG U AG AG AG ACCAG 22

lntron2-2151 17251

CFTR-

+ UGAAAGUGAAGUAGAGAGACCAG 23

lntron2-2152 17252

CFTR-

+ AUGAAAGUGAAGUAGAGAGACCAG 24

lntron2-2153 17253

CFTR-

+ AUACCAGGCCCAGAUCAG 18

lntron2-2154 17254

CFTR-

+ CAUACCAGGCCCAGAUCAG 19

lntron2-2155 17255

CFTR-

+ ACAUACCAGGCCCAGAUCAG 20

lntron2-2156 17256

CFTR-

+ CACAUACCAGGCCCAGAUCAG 21

lntron2-2157 17257

CFTR-

+ CCACAUACCAGGCCCAGAUCAG 22

lntron2-2158 17258

CFTR-

+ ACCA CAUACCAGGCCCAGAUCAG 23

lntron2-2159 17259

CFTR-

+ GACCACAUACCAGGCCCAGAUCAG 24

Intron2-2160 17260

CFTR-

+ A A AG GAG AAA U G G A U C AG 18

lntron2-2161 17261

CFTR-

+ CAAAGGAGAAAUGGAUCAG 19

lntron2-2162 17262

CFTR-

+ UCAAAGGAGAAAUGGAUCAG 20

lntron2-2163 17263

CFTR-

+ A U C A A AG GAG AAA U G G A U C AG 21

lntron2-2164 17264

CFTR-

+ C A U C A A AG GAG AAA U G G A U C AG 22

lntron2-2165 17265

CFTR-

+ C C A U C A A AG GAG AAA UGGAUCAG 23

lntron2-2166 17266

CFTR-

+ UCCAUCAAAGGAGAAAUGGAUCAG 24

lntron2-2167 17267

527

5535.1 CFTR-

+ AGGCAAUACAGACCUCAG 18

lntron2-2168 17268

CFTR-

+ AAGGCAAUACAGACCUCAG 19

lntron2-2169 17269

CFTR-

+ CAAGGCAAUACAGACCUCAG 20

Intron2-2170 17270

CFTR-

+ GCAAGGCAAUACAGACCUCAG 21

lntron2-2171 17271

CFTR-

+ AGCAAGGCAAUACAGACCUCAG 22

lntron2-2172 17272

CFTR-

+ GAGCAAGGCAAUACAGACCUCAG 23

lntron2-2173 17273

CFTR-

+ AGAGCAAGGCAAUACAGACCUCAG 24

lntron2-2174 17274

CFTR-

+ U U U U CAAACUG U ACAG AG 18

lntron2-2175 17275

CFTR-

+ AUUUUCAAACUGUACAGAG 19

lntron2-2176 17276

CFTR-

+ AAU U U U CAAACUG U ACAG AG 20

lntron2-2177 17277

CFTR-

+ U AAU U U U CAAACUG U ACAG AG 21

lntron2-2178 17278

CFTR-

+ U U AAU U U U CAAACUG U ACAG AG 22

lntron2-2179 17279

CFTR-

+ CUUAAUUUU CAAACUG U ACAG AG 23

Intron2-2180 17280

CFTR-

+ UCUUAAUUUU CAAACUG U ACAG AG 24

lntron2-2181 17281

CFTR-

+ GUAGAGAGACCAGGAGAG 18

lntron2-2182 17282

CFTR-

+ AGUAGAGAGACCAGGAGAG 19

lntron2-2183 17283

CFTR-

+ AAGUAGAGAGACCAGGAGAG 20

lntron2-2184 17284

CFTR-

+ GAAGUAGAGAGACCAGGAGAG 21

lntron2-2185 17285

CFTR-

+ UGAAGUAGAGAGACCAGGAGAG 22

lntron2-2186 17286

CFTR-

+ GUGAAGUAGAGAGACCAGGAGAG 23

lntron2-2187 17287

CFTR-

+ AG UG AAG U AG AG AG ACCAGG AG AG 24

lntron2-2188 17288

528

5535.1 CFTR-

+ AUCACUUGAACCCAGGAG 18

lntron2-2189 17289

CFTR-

+ AAUCACUUGAACCCAGGAG 19

Intron2-2190 17290

CFTR-

+ GAAUCACUUGAACCCAGGAG 20

lntron2-2191 17291

CFTR-

+ AGAAUCACUUGAACCCAGGAG 21

lntron2-2192 17292

CFTR-

+ GAGAAUCACUUGAACCCAGGAG 22

lntron2-2193 17293

CFTR-

+ GGAGAAUCACUUGAACCCAGGAG 23

lntron2-2194 17294

CFTR-

+ AGGAGAAUCACUUGAACCCAGGAG 24

lntron2-2195 17295

CFTR-

+ GAAACCAUACUUCAGGAG 18

lntron2-2196 17296

CFTR-

+ GGAAACCAUACUUCAGGAG 19

lntron2-2197 17297

CFTR-

+ UGGAAACCAUACUUCAGGAG 20

lntron2-2198 17298

CFTR-

+ GUGGAAACCAUACUUCAGGAG 21

lntron2-2199 17299

CFTR-

+ GGUGGAAACCAUACUUCAGGAG 22

Intron2-2200 17300

CFTR-

+ UGGUGGAAACCAUACUUCAGGAG 23

Intron2-2201 17301

CFTR-

+ AUGGUGGAAACCAUACUUCAGGAG 24

Intron2-2202 17302

CFTR-

+ AUGGGGUAGUUACCUGAG 18

Intron2-2203 17303

CFTR-

+ AAUGGGGUAGUUACCUGAG 19

Intron2-2204 17304

CFTR-

+ GAAUGGGGUAGUUACCUGAG 20

Intron2-2205 17305

CFTR-

+ AGAAUGGGGUAGUUACCUGAG 21

Intron2-2206 17306

CFTR-

+ UAGAAUGGGGUAGUUACCUGAG 22

Intron2-2207 17307

CFTR-

+ AUAGAAUGGGGUAGUUACCUGAG 23

Intron2-2208 17308

CFTR-

+ AAUAGAAUGGGGUAGUUACCUGAG 24

Intron2-2209 17309

529

5535.1 CFTR-

+ CCACUCAGAGUGGCUGAG 18

Intron2-2210 17310

CFTR-

+ UCCACUCAGAGUGGCUGAG 19

lntron2-2211 17311

CFTR-

+ UUCCACUCAGAGUGGCUGAG 20

lntron2-343 15443

CFTR-

+ UUUCCACUCAGAGUGGCUGAG 21

lntron2-2212 17312

CFTR-

+ CUUUCCACUCAGAGUGGCUGAG 22

lntron2-2213 17313

CFTR-

+ GCUUUCCACUCAGAGUGGCUGAG 23

lntron2-2214 17314

CFTR-

+ UGCUUUCCACUCAGAGUGGCUGAG 24

lntron2-2215 17315

CFTR-

+ GGCAGAGUUUGCAGUGAG 18

lntron2-2216 17316

CFTR-

+ AGGCAGAGUUUGCAGUGAG 19

lntron2-2217 17317

CFTR-

+ GAGGCAGAGUUUGCAGUGAG 20

lntron2-2218 17318

CFTR-

+ GGAGGCAGAGUUUGCAGUGAG 21

lntron2-2219 17319

CFTR-

+ AGGAGGCAGAGUUUGCAGUGAG 22

Intron2-2220 17320

CFTR-

+ CAGGAGGCAGAGUUUGCAGUGAG 23

lntron2-2221 17321

CFTR-

+ CCAGGAGGCAGAGUUUGCAGUGAG 24

lntron2-2222 17322

CFTR-

+ UAGGUGAUGUGGUUCUAG 18

lntron2-2223 17323

CFTR-

+ GUAGGUGAUGUGGUUCUAG 19

lntron2-2224 17324

CFTR-

+ AGUAGGUGAUGUGGUUCUAG 20

lntron2-2225 17325

CFTR-

+ GAGUAGGUGAUGUGGUUCUAG 21

lntron2-2226 17326

CFTR-

+ AGAGUAGGUGAUGUGGUUCUAG 22

lntron2-2227 17327

CFTR-

+ AAGAGUAGGUGAUGUGGUUCUAG 23

lntron2-2228 17328

CFTR-

+ CAAGAGUAGGUGAUGUGGUUCUAG 24

lntron2-2229 17329

530

5535.1 CFTR-

+ AUUUCAUGAACCACAAGG 18

I ntron2-2230 17330

CFTR-

+ AAUUUCAUGAACCACAAGG 19

lntron2-2231 17331

CFTR-

+ AAAU U U CAUG AACCACAAGG 20

lntron2-2232 17332

CFTR-

+ AAAAUUUCAUGAACCACAAGG 21

lntron2-2233 17333

CFTR-

+ AAAAAU U U CAUG AACCACAAGG 22

lntron2-2234 17334

CFTR-

+ GAAAAAUUUCAUGAACCACAAGG 23

lntron2-2235 17335

CFTR-

+ UGAAAAAUUUCAUGAACCACAAGG 24

lntron2-2236 17336

CFTR-

+ C AG A U GG G AAAG CCAAG G 18

lntron2-2237 17337

CFTR-

+ UCAGAUGGGAAAGCCAAGG 19

lntron2-2238 17338

CFTR-

+ AUCAGAUGGGAAAGCCAAGG 20

lntron2-2239 17339

CFTR-

+ GAUCAGAUGGGAAAGCCAAGG 21

Intron2-2240 17340

CFTR-

+ GGAUCAGAUGGGAAAGCCAAGG 22

lntron2-2241 17341

CFTR-

+ UGGAUCAGAUGGGAAAGCCAAGG 23

lntron2-2242 17342

CFTR-

+ AUGGAUCAGAUGGGAAAGCCAAGG 24

lntron2-2243 17343

CFTR-

+ CCUGAGGAGAAGGCAAGG 18

lntron2-2244 17344

CFTR-

+ ACCUGAGGAGAAGGCAAGG 19

lntron2-2245 17345

CFTR-

+ UACCUGAGGAGAAGGCAAGG 20

lntron2-2246 17346

CFTR-

+ UUACCUGAGGAGAAGGCAAGG 21

lntron2-2247 17347

CFTR-

+ GU UACCUGAGGAGAAGGCAAGG 22

lntron2-2248 17348

CFTR-

+ AGUUACCUGAGGAGAAGGCAAGG 23

lntron2-2249 17349

CFTR-

+ UAGUUACCUGAGGAGAAGGCAAGG 24

Intron2-2250 17350

531

5535.1 CFTR-

+ AAG AAAAG AAG U AACAGG 18

l ntron2-2251 17351

CFTR-

+ U AAG AAAAG AAG U AACAGG 19

lntron2-2252 17352

CFTR-

+ AUAAGAAAAGAAGUAACAGG 20

lntron2-2253 17353

CFTR-

+ UAUAAGAAAAGAAGUAACAGG 21

lntron2-2254 17354

CFTR-

+ U U AUAAGAAAAGAAGUAACAGG 22

lntron2-2255 17355

CFTR-

+ U UUAUAAGAAAAGAAGUAACAGG 23

lntron2-2256 17356

CFTR-

+ U U U UAU AAG AAAAG AAG U AACAGG 24

lntron2-2257 17357

CFTR-

+ ACCCAGCUACUCGAGAGG 18

lntron2-2258 17358

CFTR-

+ AACCCAGCUACUCGAGAGG 19

lntron2-2259 17359

CFTR-

+ AAACCCAGCUACUCGAGAGG 20

Intron2-2260 17360

CFTR-

+ UAAACCCAGCUACUCGAGAGG 21

lntron2-2261 17361

CFTR-

+ GUAAACCCAGCUACUCGAGAGG 22

lntron2-2262 17362

CFTR-

+ UGUAAACCCAGCUACUCGAGAGG 23

lntron2-2263 17363

CFTR-

+ CUGUAAACCCAGCUACUCGAGAGG 24

lntron2-2264 17364

CFTR-

+ CUACUCGAGAGGCUGAGG 18

lntron2-2265 17365

CFTR-

+ GCUACUCGAGAGGCUGAGG 19

lntron2-2266 17366

CFTR-

+ AGCUACUCGAGAGGCUGAGG 20

lntron2-2267 17367

CFTR-

+ CAGCUACUCGAGAGGCUGAGG 21

lntron2-2268 17368

CFTR-

+ CCAGCUACUCGAGAGGCUGAGG 22

lntron2-2269 17369

CFTR-

+ CCCAGCUACUCGAGAGGCUGAGG 23

Intron2-2270 17370

CFTR-

+ ACCCAGCUACUCGAGAGGCUGAGG 24

lntron2-2271 17371

532

5535.1 CFTR-

+ CUCUAAAGGAGUAAUAGG 18

lntron2-2272 17372

CFTR-

+ ACUCUAAAGGAGUAAUAGG 19

lntron2-2273 17373

CFTR-

+ CACUCUAAAGGAGUAAUAGG 20

lntron2-2274 17374

CFTR-

+ UCACUCUAAAGGAGUAAUAGG 21

lntron2-2275 17375

CFTR-

+ AUCACUCUAAAGGAGUAAUAGG 22

lntron2-2276 17376

CFTR-

+ AAUCACUCUAAAGGAGUAAUAGG 23

lntron2-2277 17377

CFTR-

+ AAAUCACUCUAAAGGAGUAAUAGG 24

lntron2-2278 17378

CFTR-

+ AGGCCCAGAUCAGAAGGG 18

lntron2-2279 17379

CFTR-

+ CAGGCCCAGAUCAGAAGGG 19

Intron2-2280 17380

CFTR-

+ CCAGGCCCAGAUCAGAAGGG 20

lntron2-2281 17381

CFTR-

+ ACCAGGCCCAGAUCAGAAGGG 21

lntron2-2282 17382

CFTR-

+ UACCAGGCCCAGAUCAGAAGGG 22

lntron2-2283 17383

CFTR-

+ AUACCAGGCCCAGAUCAGAAGGG 23

lntron2-2284 17384

CFTR-

+ CAUACCAGGCCCAGAUCAGAAGGG 24

lntron2-2285 17385

CFTR-

+ AGAAAAGAAGUAACAGGG 18

lntron2-2286 17386

CFTR-

+ AAGAAAAGAAGUAACAGGG 19

lntron2-2287 17387

CFTR-

+ UAAGAAAAGAAGUAACAGGG 20

lntron2-681 15781

CFTR-

+ AU AAGAAAAGAAGUAACAGGG 21

lntron2-2288 17388

CFTR-

+ UAU AAGAAAAGAAGUAACAGGG 22

lntron2-2289 17389

CFTR-

+ UUAUAAGAAAAGAAGUAACAGGG 23

Intron2-2290 17390

CFTR-

+ UUUAUAAGAAAAGAAGUAACAGGG 24

lntron2-2291 17391

533

5535.1 CFTR-

+ UGAGAGAUUCUUUAUGGG 18

lntron2-2292 17392

CFTR-

+ CUGAGAGAUUCUUUAUGGG 19

lntron2-2293 17393

CFTR-

+ ACUGAGAGAUUCUUUAUGGG 20

lntron2-353 15453

CFTR-

+ AACUGAGAGAUUCUUUAUGGG 21

lntron2-2294 17394

CFTR-

+ AAACUGAGAGAUUCUUUAUGGG 22

lntron2-2295 17395

CFTR-

+ GAAACUGAGAGAUUCUUUAUGGG 23

lntron2-2296 17396

CFTR-

+ GGAAACUGAGAGAUUCUUUAUGGG 24

lntron2-2297 17397

CFTR-

+ GGGGAAUUUCUUUAAUGG 18

lntron2-2298 17398

CFTR-

+ CGGGGAAUUUCUUUAAUGG 19

lntron2-2299 17399

CFTR-

+ UCGGGGAAUUUCUUUAAUGG 20

Intron2-2300 17400

CFTR-

+ GUCGGGGAAUUUCUUUAAUGG 21

Intron2-2301 17401

CFTR-

+ GGUCGGGGAAUUUCUUUAAUGG 22

Intron2-2302 17402

CFTR-

+ AGGUCGGGGAAUUUCUUUAAUGG 23

Intron2-2303 17403

CFTR-

+ AAGGUCGGGGAAUUUCUUUAAUGG 24

Intron2-2304 17404

CFTR-

+ GUAGUUUUAGGAACAUGG 18

Intron2-2305 17405

CFTR-

+ UGUAGUUUUAGGAACAUGG 19

Intron2-2306 17406

CFTR-

+ AUGUAGUUUUAGGAACAUGG 20

lntron2-355 15455

CFTR-

+ AAUGUAGUUUUAGGAACAUGG 21

Intron2-2307 17407

CFTR-

+ CAAUGUAGUUUUAGGAACAUGG 22

Intron2-2308 17408

CFTR-

+ GCAAUGUAGUUUUAGGAACAUGG 23

Intron2-2309 17409

CFTR-

+ GGCAAUGUAGUUUUAGGAACAUGG 24

Intron2-2310 17410 CFTR-

+ CUGAGAGAUUCUUUAUGG 18

lntron2-2311 17411

CFTR-

+ ACUGAGAGAUUCUUUAUGG 19

lntron2-2312 17412

CFTR-

+ AACUGAGAGAUUCUUUAUGG 20

lntron2-356 15456

CFTR-

+ AAACUGAGAGAUUCUUUAUGG 21

lntron2-2313 17413

CFTR-

+ GAAACUGAGAGAUUCUUUAUGG 22

lntron2-2314 17414

CFTR-

+ GGAAACUGAGAGAUUCUUUAUGG 23

lntron2-2315 17415

CFTR-

+ AGGAAACUGAGAGAUUCUUUAUGG 24

lntron2-2316 17416

CFTR-

+ AAAUAGUCUGAAAACUGG 18

lntron2-2317 17417

CFTR-

+ UAAAUAGUCUGAAAACUGG 19

lntron2-2318 17418

CFTR-

+ UUAAAUAGUCUGAAAACUGG 20

lntron2-2319 17419

CFTR-

+ AUUAAAUAGUCUGAAAACUGG 21

Intron2-2320 17420

CFTR-

+ CAUUAAAUAGUCUGAAAACUGG 22

lntron2-2321 17421

CFTR-

+ ACAUUAAAUAGUCUGAAAACUGG 23

lntron2-2322 17422

CFTR-

+ GACAUUAAAUAGUCUGAAAACUGG 24

lntron2-2323 17423

CFTR-

+ GCUUUCCACUCAGAGUGG 18

lntron2-2324 17424

CFTR-

+ UGCUUUCCACUCAGAGUGG 19

lntron2-2325 17425

CFTR-

+ AUGCUUUCCACUCAGAGUGG 20

lntron2-2326 17426

CFTR-

+ GAUGCUUUCCACUCAGAGUGG 21

lntron2-2327 17427

CFTR-

+ UGAUGCUUUCCACUCAGAGUGG 22

lntron2-2328 17428

CFTR-

+ AUGAUGCUUUCCACUCAGAGUGG 23

lntron2-2329 17429

CFTR-

+ AAUGAUGCUUUCCACUCAGAGUGG 24

Intron2-2330 17430 CFTR-

+ GUCCACACGGAAGUAAUG 18

lntron2-2331 17431

CFTR-

+ GGUCCACACGGAAGUAAUG 19

lntron2-2332 17432

CFTR-

+ UGGUCCACACGGAAGUAAUG 20

lntron2-2333 17433

CFTR-

+ GUGGUCCACACGGAAGUAAUG 21

lntron2-2334 17434

CFTR-

+ AGUGGUCCACACGGAAGUAAUG 22

lntron2-2335 17435

CFTR-

+ AAGUGGUCCACACGGAAGUAAUG 23

lntron2-2336 17436

CFTR-

+ AAAGUGGUCCACACGGAAGUAAUG 24

lntron2-2337 17437

CFTR-

+ ACCAGCCUGGCCAACAUG 18

lntron2-2338 17438

CFTR-

+ GACCAGCCUGGCCAACAUG 19

lntron2-2339 17439

CFTR-

+ AGACCAGCCUGGCCAACAUG 20

Intron2-2340 17440

CFTR-

+ AAGACCAGCCUGGCCAACAUG 21

lntron2-2341 17441

CFTR-

+ CAAGACCAGCCUGGCCAACAUG 22

lntron2-2342 17442

CFTR-

+ UCAAGACCAGCCUGGCCAACAUG 23

lntron2-2343 17443

CFTR-

+ UUCAAGACCAGCCUGGCCAACAUG 24

lntron2-2344 17444

CFTR-

+ UGUAGUUUUAGGAACAUG 18

lntron2-2345 17445

CFTR-

+ AUGUAGUUUUAGGAACAUG 19

lntron2-2346 17446

CFTR-

+ AAUGUAGUUUUAGGAACAUG 20

lntron2-2347 17447

CFTR-

+ CAAUGUAGUUUUAGGAACAUG 21

lntron2-2348 17448

CFTR-

+ GCAAUGUAGUUUUAGGAACAUG 22

lntron2-2349 17449

CFTR-

+ GGCAAUGUAGUUUUAGGAACAUG 23

Intron2-2350 17450

CFTR-

+ GGGCAAUGUAGUUUUAGGAACAUG 24

lntron2-2351 17451

536

5535.1 CFTR-

+ UUGCACACUGCAGUUAUG 18

lntron2-2352 17452

CFTR-

+ UUUGCACACUGCAGUUAUG 19

lntron2-2353 17453

CFTR-

+ GUUUGCACACUGCAGUUAUG 20

lntron2-2354 17454

CFTR-

+ GGUUUGCACACUGCAGUUAUG 21

lntron2-2355 17455

CFTR-

+ UGGUUUGCACACUGCAGUUAUG 22

lntron2-2356 17456

CFTR-

+ GUGGUUUGCACACUGCAGUUAUG 23

lntron2-2357 17457

CFTR-

+ UGUGGUUUGCACACUGCAGUUAUG 24

lntron2-2358 17458

CFTR-

+ CCAGGGACCCACUUUAUG 18

lntron2-2359 17459

CFTR-

+ ACCAGGGACCCACUUUAUG 19

Intron2-2360 17460

CFTR-

+ AACCAGGGACCCACUUUAUG 20

lntron2-2361 17461

CFTR-

+ UAACCAGGGACCCACUUUAUG 21

lntron2-2362 17462

CFTR-

+ CUAACCAGGGACCCACUUUAUG 22

lntron2-2363 17463

CFTR-

+ UCUAACCAGGGACCCACUUUAUG 23

lntron2-2364 17464

CFTR-

+ UUCUAACCAGGGACCCACUUUAUG 24

lntron2-2365 17465

CFTR-

+ ACUGAGAGAUUCUUUAUG 18

lntron2-2366 17466

CFTR-

+ AACUGAGAGAUUCUUUAUG 19

lntron2-2367 17467

CFTR-

+ AAACUGAGAGAUUCUUUAUG 20

lntron2-361 15461

CFTR-

+ GAAACUGAGAGAUUCUUUAUG 21

lntron2-2368 17468

CFTR-

+ GGAAACUGAGAGAUUCUUUAUG 22

lntron2-2369 17469

CFTR-

+ AGGAAACUGAGAGAUUCUUUAUG 23

Intron2-2370 17470

CFTR-

+ AAGGAAACUGAGAGAUUCUUUAUG 24

lntron2-2371 17471

537

5535.1 CFTR-

+ GAAUGGGGUAGUUACCUG 18

lntron2-2372 17472

CFTR-

+ AGAAUGGGGUAGUUACCUG 19

lntron2-2373 17473

CFTR-

+ UAGAAUGGGGUAGUUACCUG 20

lntron2-362 15462

CFTR-

+ AUAGAAUGGGGUAGUUACCUG 21

lntron2-2374 17474

CFTR-

+ AAUAGAAUGGGGUAGUUACCUG 22

lntron2-2375 17475

CFTR-

+ AAAUAGAAUGGGGUAGUUACCUG 23

lntron2-2376 17476

CFTR-

+ AAAAUAGAAUGGGGUAGUUACCUG 24

lntron2-2377 17477

CFTR-

+ GGUCACUUCCCAAGGGUG 18

lntron2-2378 17478

CFTR-

+ GGGUCACUUCCCAAGGGUG 19

lntron2-2379 17479

CFTR-

+ AGGGUCACUUCCCAAGGGUG 20

Intron2-2380 17480

CFTR-

+ CAGGGUCACUUCCCAAGGGUG 21

lntron2-2381 17481

CFTR-

+ CCAGGGUCACUUCCCAAGGGUG 22

lntron2-2382 17482

CFTR-

+ GCCAGGGUCACUUCCCAAGGGUG 23

lntron2-2383 17483

CFTR-

+ AGCCAGGGUCACUUCCCAAGGGUG 24

lntron2-2384 17484

CFTR-

+ UAAAGGUCUUUGAAAAAU 18

lntron2-2385 17485

CFTR-

+ U U AAAGG U CU U UG AAAAAU 19

lntron2-2386 17486

CFTR-

+ AUUAAAGGUCUUUGAAAAAU 20

lntron2-2387 17487

CFTR-

+ UAUUAAAGGUCUUUGAAAAAU 21

lntron2-2388 17488

CFTR-

+ GUAUUAAAGGUCUUUGAAAAAU 22

lntron2-2389 17489

CFTR-

+ UGUAUUAAAGGUCUUUGAAAAAU 23

Intron2-2390 17490

CFTR-

+ AUG U AU U AAAGG U CU U UG AAAAAU 24

lntron2-2391 17491

538

5535.1 CFTR-

+ ACAAGG CAG U U AUG AAAU 18

lntron2-2392 17492

CFTR-

+ CACAAGG CAG U U AUG AAAU 19

lntron2-2393 17493

CFTR-

+ U CACAAGG CAG U U AUG AAAU 20

lntron2-2394 17494

CFTR-

+ GUCACAAGGCAGUUAUGAAAU 21

lntron2-2395 17495

CFTR-

+ GGUCACAAGGCAGUUAUGAAAU 22

lntron2-2396 17496

CFTR-

+ UGGUCACAAGGCAGUUAUGAAAU 23

lntron2-2397 17497

CFTR-

+ AUGGUCACAAGGCAGUUAUGAAAU 24

lntron2-2398 17498

CFTR-

+ CAGAGUAAGAAGCUAAAU 18

lntron2-2399 17499

CFTR-

+ UCAGAGUAAGAAGCU AAA U 19

Intron2-2400 17500

CFTR-

+ CUCAGAGUAAGAAGCUAAAU 20

Intron2-2401 17501

CFTR-

+ ACUCAGAGUAAGAAGCUAAAU 21

Intron2-2402 17502

CFTR-

+ UACUCAGAGUAAGAAGCUAAAU 22

Intron2-2403 17503

CFTR-

+ UUACUCAGAGUAAGAAGCUAAAU 23

Intron2-2404 17504

CFTR-

+ GUUACUCAGAGUAAGAAGCUAAAU 24

Intron2-2405 17505

CFTR-

+ CAACAAAAUGGGUUCAAU 18

Intron2-2406 17506

CFTR-

+ CCAACAAAAUGGGUUCAAU 19

Intron2-2407 17507

CFTR-

+ ACCAACAAAAUGGGUUCAAU 20

Intron2-2408 17508

CFTR-

+ AACCAACAAAAUGGGUUCAAU 21

Intron2-2409 17509

CFTR-

+ AAACCAACAAAAUGGGUUCAAU 22

Intron2-2410 17510

CFTR-

+ UAAACCAACAAAAUGGGUUCAAU 23

lntron2-2411 17511

CFTR-

+ AUAAACCAACAAAAUGGGUUCAAU 24

lntron2-2412 17512

539

5535.1 CFTR-

+ CCCUAGAAGCUUGCUAAU 18

lntron2-2413 17513

CFTR-

+ CCCCUAGAAGCUUGCUAAU 19

lntron2-2414 17514

CFTR-

+ UCCCCUAGAAGCUUGCUAAU 20

lntron2-2415 17515

CFTR-

+ AUCCCCUAGAAGCUUGCUAAU 21

lntron2-2416 17516

CFTR-

+ CAUCCCCUAGAAGCUUGCUAAU 22

lntron2-2417 17517

CFTR-

+ GCAUCCCCUAGAAGCUUGCUAAU 23

lntron2-2418 17518

CFTR-

+ GGCAUCCCCUAGAAGCUUGCUAAU 24

lntron2-2419 17519

CFTR-

+ U U U AAAU UG AAU CAACAU 18

Intron2-2420 17520

CFTR-

+ U U U U AAAU UG AAU CAACAU 19

lntron2-2421 17521

CFTR-

+ U U U U U AAAU UG AAU CAACAU 20

lntron2-699 15799

CFTR-

+ U U U U U U AAAU UG AAU CAACAU 21

lntron2-2422 17522

CFTR-

+ AU U U U U U AAAU UG AAU CAACAU 22

lntron2-2423 17523

CFTR-

+ U AU U U U U U AAAU UG AAU CAACAU 23

lntron2-2424 17524

CFTR-

+ AUAUUUUU U AAAU UG AAU CAACAU 24

lntron2-2425 17525

CFTR-

+ GGUGUUGUUAUAUUUCAU 18

lntron2-2426 17526

CFTR-

+ AGGUGUUGUUAUAUUUCAU 19

lntron2-2427 17527

CFTR-

+ AAGGUGUUGUUAUAUUUCAU 20

lntron2-2428 17528

CFTR-

+ AAAGGUGUUGUUAUAUUUCAU 21

lntron2-2429 17529

CFTR-

+ GAAAGGUGUUGUUAUAUUUCAU 22

Intron2-2430 17530

CFTR-

+ AGAAAGGUGUUGUUAUAUUUCAU 23

lntron2-2431 17531

CFTR-

+ UAGAAAGGUGUUGUUAUAUUUCAU 24

lntron2-2432 17532

540

5535.1 CFTR-

+ UUCGUGGUCCUUAAAGAU 18

lntron2-2433 17533

CFTR-

+ UUUCGUGGUCCUUAAAGAU 19

lntron2-2434 17534

CFTR-

+ CUUUCGUGGUCCUUAAAGAU 20

lntron2-375 15475

CFTR-

+ UCUUUCGUGGUCCUUAAAGAU 21

lntron2-2435 17535

CFTR-

+ UUCUUUCGUGGUCCUUAAAGAU 22

lntron2-2436 17536

CFTR-

+ CUUCUUUCGUGGUCCUUAAAGAU 23

lntron2-2437 17537

CFTR-

+ CCUUCUUUCGUGGUCCUUAAAGAU 24

lntron2-2438 17538

CFTR-

+ CACAUACCAGGCCCAGAU 18

lntron2-2439 17539

CFTR-

+ CCACAUACCAGGCCCAGAU 19

Intron2-2440 17540

CFTR-

+ ACCACAUACCAGGCCCAGAU 20

lntron2-2441 17541

CFTR-

+ GACCACAUACCAGGCCCAGAU 21

lntron2-2442 17542

CFTR-

+ GGACCACAUACCAGGCCCAGAU 22

lntron2-2443 17543

CFTR-

+ AGGACCACAUACCAGGCCCAGAU 23

lntron2-2444 17544

CFTR-

+ UAGGACCACAUACCAGGCCCAGAU 24

lntron2-2445 17545

CFTR-

+ AGGAGAAAUGGAUCAGAU 18

lntron2-2446 17546

CFTR-

+ AAGGAGAAAUGGAUCAGAU 19

lntron2-2447 17547

CFTR-

+ AAAGGAGAAAUGGAUCAGAU 20

lntron2-376 15476

CFTR-

+ C A A AG GAG AAA UGGAUCAGAU 21

lntron2-2448 17548

CFTR-

+ U C A A AG GAG AAA UGGAUCAGAU 22

lntron2-2449 17549

CFTR-

+ AUCAAAGGAGAAAUGGAUCAGAU 23

Intron2-2450 17550

CFTR-

+ CAUCAAAGGAGAAAUGGAUCAGAU 24

lntron2-2451 17551

541

5535.1 CFTR-

+ GUAAUACACAGCUGAGAU 18

lntron2-2452 17552

CFTR-

+ AGUAAUACACAGCUGAGAU 19

lntron2-2453 17553

CFTR-

+ GAGUAAUACACAGCUGAGAU 20

lntron2-2454 17554

CFTR-

+ GGAGUAAUACACAGCUGAGAU 21

lntron2-2455 17555

CFTR-

+ AGGAGUAAUACACAGCUGAGAU 22

lntron2-2456 17556

CFTR-

+ AAGGAGUAAUACACAGCUGAGAU 23

lntron2-2457 17557

CFTR-

+ AAAGGAGUAAUACACAGCUGAGAU 24

lntron2-2458 17558

CFTR-

+ GGAUCCUAACCUUUUGAU 18

lntron2-2459 17559

CFTR-

+ AGGAUCCUAACCUUUUGAU 19

Intron2-2460 17560

CFTR-

+ AAGGAUCCUAACCUUUUGAU 20

lntron2-379 15479

CFTR-

+ AAAGGAUCCUAACCUUUUGAU 21

lntron2-2461 17561

CFTR-

+ AAAAGGAUCCUAACCUUUUGAU 22

lntron2-2462 17562

CFTR-

+ CAAAAGGAUCCUAACCUUUUGAU 23

lntron2-2463 17563

CFTR-

+ UCAAAAGGAUCCUAACCUUUUGAU 24

lntron2-2464 17564

CFTR-

+ UUUUCUUUUAAAUACUAU 18

lntron2-2465 17565

CFTR-

+ GUUUUCUUUUAAAUACUAU 19

lntron2-2466 17566

CFTR-

+ UGUUUUCUUUUAAAUACUAU 20

Intron2-700 15800

CFTR-

+ CUGUUUUCUUUUAAAUACUAU 21

lntron2-2467 17567

CFTR-

+ UCUGUUUUCUUUUAAAUACUAU 22

lntron2-2468 17568

CFTR-

+ UUCUGUUUUCUUUUAAAUACUAU 23

lntron2-2469 17569

CFTR-

+ UUUCUGUUUUCUUUUAAAUACUAU 24

Intron2-2470 17570

542

5535.1 CFTR-

+ AACUGAGAGAUUCUUUAU 18

lntron2-2471 17571

CFTR-

+ AAACUGAGAGAUUCUUUAU 19

lntron2-2472 17572

CFTR-

+ GAAACUGAGAGAUUCUUUAU 20

lntron2-73 15173

CFTR-

+ GGAAACUGAGAGAUUCUUUAU 21

lntron2-2473 17573

CFTR-

+ AGGAAACUGAGAGAUUCUUUAU 22

lntron2-2474 17574

CFTR-

+ AAGGAAACUGAGAGAUUCUUUAU 23

lntron2-2475 17575

CFTR-

+ AAAGGAAACUGAGAGAUUCUUUAU 24

lntron2-2476 17576

CFTR-

+ U U CAAAU ACCAAU U U U AU 18

lntron2-2477 17577

CFTR-

+ U U U CAAAU ACCAAU U U U AU 19

lntron2-2478 17578

CFTR-

+ AU U U CAAAU ACCAAU U U U AU 20

lntron2-2479 17579

CFTR-

+ AAUUU CAAAU ACCAAU U U U AU 21

Intron2-2480 17580

CFTR-

+ AAAU U U CAAAU ACCAAU U U U AU 22

lntron2-2481 17581

CFTR-

+ U AAAU U U CAAAU ACCAAU U U U AU 23

lntron2-2482 17582

CFTR-

+ AU AAAU U U CAAAU ACCAAU U U U AU 24

lntron2-2483 17583

CFTR-

+ UUGAUUGGAAAGGAAACU 18

lntron2-2484 17584

CFTR-

+ UUUGAUUGGAAAGGAAACU 19

lntron2-2485 17585

CFTR-

+ UUUUGAUUGGAAAGGAAACU 20

lntron2-2486 17586

CFTR-

+ CUUUUGAUUGGAAAGGAAACU 21

lntron2-2487 17587

CFTR-

+ CCUUUUGAUUGGAAAGGAAACU 22

lntron2-2488 17588

CFTR-

+ ACCU UUUGAUUGGAAAGGAAACU 23

lntron2-2489 17589

CFTR-

+ AACCUUUUGAUUGGAAAGGAAACU 24

Intron2-2490 17590

543

5535.1 CFTR-

+ GCCACUAAUCCCAACACU 18

l ntron2-2491 17591

CFTR-

+ CGCCACUAAUCCCAACACU 19

lntron2-2492 17592

CFTR-

+ ACGCCACUAAUCCCAACACU 20

lntron2-2493 17593

CFTR-

+ CACGCCACUAAUCCCAACACU 21

lntron2-2494 17594

CFTR-

+ UCACGCCACUAAUCCCAACACU 22

lntron2-2495 17595

CFTR-

+ CUCACGCCACUAAUCCCAACACU 23

lntron2-2496 17596

CFTR-

+ GCUCACGCCACUAAUCCCAACACU 24

lntron2-2497 17597

CFTR-

+ GGCCCUAU UCUAGGCACU 18

lntron2-2498 17598

CFTR-

+ AGGCCCUAUUCUAGGCACU 19

lntron2-2499 17599

CFTR-

+ CAGGCCCUAUUCUAGGCACU 20

I ntron2-703 15803

CFTR-

+ CCAGGCCCUAU UCUAGGCACU 21

Intron2-2500 17600

CFTR-

+ GCCAGGCCCUAUUCUAGGCACU 22

Intron2-2501 17601

CFTR-

+ UGCCAGGCCCUAUUCUAGGCACU 23

Intron2-2502 17602

CFTR-

+ AUGCCAGGCCCUAUUCUAGGCACU 24

Intron2-2503 17603

CFTR-

+ CCUGUAGUCCCAGCUACU 18

Intron2-2504 17604

CFTR-

+ GCCUGUAGUCCCAGCUACU 19

Intron2-2505 17605

CFTR-

+ UGCCUGUAGUCCCAGCUACU 20

Intron2-2506 17606

CFTR-

+ AUGCCUGUAGUCCCAGCUACU 21

Intron2-2507 17607

CFTR-

+ CAUGCCUGUAGUCCCAGCUACU 22

Intron2-2508 17608

CFTR-

+ GCAUGCCUGUAGUCCCAGCUACU 23

Intron2-2509 17609

CFTR-

+ UGCAUGCCUGUAGUCCCAGCUACU 24

Intron2-2510 17610

544

5535.1 CFTR-

+ AGAAUGGGGUAGUUACCU 18

lntron2-2511 17611

CFTR-

+ UAGAAUGGGGUAGUUACCU 19

lntron2-2512 17612

CFTR-

+ AUAGAAUGGGGUAGUUACCU 20

lntron2-2513 17613

CFTR-

+ AAUAGAAUGGGGUAGUUACCU 21

lntron2-2514 17614

CFTR-

+ AAAUAGAAUGGGGUAGUUACCU 22

lntron2-2515 17615

CFTR-

+ AAAAUAGAAUGGGGUAGUUACCU 23

lntron2-2516 17616

CFTR-

+ AAAAAUAGAAUGGGGUAGUUACCU 24

lntron2-2517 17617

CFTR-

+ GAGCAGAGAAUGUUAGCU 18

lntron2-2518 17618

CFTR-

+ AGAGCAGAGAAUGUUAGCU 19

lntron2-2519 17619

CFTR-

+ GAGAGCAGAGAAUGUUAGCU 20

Intron2-2520 17620

CFTR-

+ GGAGAGCAGAGAAUGUUAGCU 21

lntron2-2521 17621

CFTR-

+ AGGAGAGCAGAGAAUGUUAGCU 22

lntron2-2522 17622

CFTR-

+ CAGGAGAGCAGAGAAUGUUAGCU 23

lntron2-2523 17623

CFTR-

+ CCAGGAGAGCAGAGAAUGUUAGCU 24

lntron2-2524 17624

CFTR-

+ UUUCCACUCAGAGUGGCU 18

lntron2-2525 17625

CFTR-

+ CUUUCCACUCAGAGUGGCU 19

lntron2-2526 17626

CFTR-

+ GCUUUCCACUCAGAGUGGCU 20

lntron2-2527 17627

CFTR-

+ UGCUUUCCACUCAGAGUGGCU 21

lntron2-2528 17628

CFTR-

+ AUGCUUUCCACUCAGAGUGGCU 22

lntron2-2529 17629

CFTR-

+ GAUGCUUUCCACUCAGAGUGGCU 23

Intron2-2530 17630

CFTR-

+ UGAUGCUUUCCACUCAGAGUGGCU 24

lntron2-2531 17631

545

5535.1 CFTR-

+ AUAUCCUGACUACAAUCU 18

lntron2-2532 17632

CFTR-

+ CAUAUCCUGACUACAAUCU 19

lntron2-2533 17633

CFTR-

+ UCAUAUCCUGACUACAAUCU 20

lntron2-395 15495

CFTR-

+ UUCAUAUCCUGACUACAAUCU 21

lntron2-2534 17634

CFTR-

+ GUUCAUAUCCUGACUACAAUCU 22

lntron2-2535 17635

CFTR-

+ AGUUCAUAUCCUGACUACAAUCU 23

lntron2-2536 17636

CFTR-

+ AAGUUCAUAUCCUGACUACAAUCU 24

lntron2-2537 17637

CFTR-

+ GAAGCUGGCCCUUGAUCU 18

lntron2-2538 17638

CFTR-

+ AGAAGCUGGCCCUUGAUCU 19

lntron2-2539 17639

CFTR-

+ UAGAAGCUGGCCCUUGAUCU 20

Intron2-2540 17640

CFTR-

+ AUAGAAGCUGGCCCUUGAUCU 21

lntron2-2541 17641

CFTR-

+ AAUAGAAGCUGGCCCUUGAUCU 22

lntron2-2542 17642

CFTR-

+ UAAUAGAAGCUGGCCCUUGAUCU 23

lntron2-2543 17643

CFTR-

+ AUAAUAGAAGCUGGCCCUUGAUCU 24

lntron2-2544 17644

CFTR-

+ GCAAAGUAUAUUAUCUCU 18

lntron2-2545 17645

CFTR-

+ GGCAAAGUAUAUUAUCUCU 19

lntron2-2546 17646

CFTR-

+ UGGCAAAGUAUAUUAUCUCU 20

lntron2-2547 17647

CFTR-

+ CUGGCAAAGUAUAUUAUCUCU 21

lntron2-2548 17648

CFTR-

+ ACUGGCAAAGUAUAUUAUCUCU 22

lntron2-2549 17649

CFTR-

+ AACUGGCAAAGUAUAUUAUCUCU 23

Intron2-2550 17650

CFTR-

+ UAACUGGCAAAGUAUAUUAUCUCU 24

lntron2-2551 17651

546

5535.1 CFTR-

+ ACUAUGACUCAAGAGUCU 18

lntron2-2552 17652

CFTR-

+ CACUAUGACUCAAGAGUCU 19

lntron2-2553 17653

CFTR-

+ GCACUAUGACUCAAGAGUCU 20

lntron2-2554 17654

CFTR-

+ AGCACUAUGACUCAAGAGUCU 21

lntron2-2555 17655

CFTR-

+ AAGCACUAUGACUCAAGAGUCU 22

lntron2-2556 17656

CFTR-

+ UAAGCACUAUGACUCAAGAGUCU 23

lntron2-2557 17657

CFTR-

+ GUAAGCACUAUGACUCAAGAGUCU 24

lntron2-2558 17658

CFTR-

+ AUCAUGUAUUAAAGGUCU 18

lntron2-2559 17659

CFTR-

+ AAUCAUGUAUUAAAGGUCU 19

Intron2-2560 17660

CFTR-

+ AAAUCAUGUAUUAAAGGUCU 20

lntron2-2561 17661

CFTR-

+ AAAAUCAUGUAUUAAAGGUCU 21

lntron2-2562 17662

CFTR-

+ UAAAAUCAUGUAUUAAAGGUCU 22

lntron2-2563 17663

CFTR-

+ CUAAAAUCAUGUAUUAAAGGUCU 23

lntron2-2564 17664

CFTR-

+ ACUAAAAUCAUGUAUUAAAGGUCU 24

lntron2-2565 17665

CFTR-

+ AGAAAGCUGGUCCGGUCU 18

lntron2-2566 17666

CFTR-

+ UAGAAAGCUGGUCCGGUCU 19

lntron2-2567 17667

CFTR-

+ GUAGAAAGCUGGUCCGGUCU 20

lntron2-2568 17668

CFTR-

+ UGUAGAAAGCUGGUCCGGUCU 21

lntron2-2569 17669

CFTR-

+ AUGUAGAAAGCUGGUCCGGUCU 22

Intron2-2570 17670

CFTR-

+ UAUGUAGAAAGCUGGUCCGGUCU 23

lntron2-2571 17671

CFTR-

+ UUAUGUAGAAAGCUGGUCCGGUCU 24

lntron2-2572 17672

547

5535.1 CFTR-

+ U CU AAU AAG ACAAAU U CU 18

lntron2-2573 17673

CFTR-

+ CUCUAAUAAGACAAAUUCU 19

lntron2-2574 17674

CFTR-

+ UCUCUAAUAAGACAAAUUCU 20

lntron2-2575 17675

CFTR-

+ GUCUCUAAUAAGACAAAUUCU 21

lntron2-2576 17676

CFTR-

+ GGUCUCUAAUAAGACAAAUUCU 22

lntron2-2577 17677

CFTR-

+ UGGUCUCUAAUAAGACAAAUUCU 23

lntron2-2578 17678

CFTR-

+ AUGGUCUCUAAUAAGACAAAUUCU 24

lntron2-2579 17679

CFTR-

+ CAUUUGGUUACUCAGAGU 18

Intron2-2580 17680

CFTR-

+ ACAUUUGGUUACUCAGAGU 19

lntron2-2581 17681

CFTR-

+ AACAUUUGGUUACUCAGAGU 20

lntron2-2582 17682

CFTR-

+ UAACAUUUGGUUACUCAGAGU 21

lntron2-2583 17683

CFTR-

+ AUAACAUUUGGUUACUCAGAGU 22

lntron2-2584 17684

CFTR-

+ CAUAACAUUUGGUUACUCAGAGU 23

lntron2-2585 17685

CFTR-

+ CCAU AACAU U UGG U U ACU CAG AG U 24

lntron2-2586 17686

CFTR-

+ G AAU AG ACAU U AAAU AG U 18

lntron2-2587 17687

CFTR-

+ AGAAUAGACAUUAAAUAGU 19

lntron2-2588 17688

CFTR-

+ AAG AAU AG ACAU U AAAU AG U 20

lntron2-2589 17689

CFTR-

+ U AAG AAU AG ACAU U AAAU AG U 21

Intron2-2590 17690

CFTR-

+ G U AAG AAU AG ACAU U AAAU AG U 22

lntron2-2591 17691

CFTR-

+ AG U AAG AAU AG ACAU U AAAU AG U 23

lntron2-2592 17692

CFTR-

+ U AG U AAG AAU AG ACAU U AAAU AG U 24

lntron2-2593 17693

548

5535.1 CFTR-

+ CUGAGGAGAAGGCAAGGU 18

lntron2-2594 17694

CFTR-

+ CCUGAGGAGAAGGCAAGGU 19

lntron2-2595 17695

CFTR-

+ ACCUGAGGAGAAGGCAAGGU 20

Intron2-405 15505

CFTR-

+ UACCUGAGGAGAAGGCAAGGU 21

lntron2-2596 17696

CFTR-

+ UUACCUGAGGAGAAGGCAAGGU 22

lntron2-2597 17697

CFTR-

+ GU UACCUGAGGAGAAGGCAAGGU 23

lntron2-2598 17698

CFTR-

+ AGUUACCUGAGGAGAAGGCAAGGU 24

lntron2-2599 17699

CFTR-

+ GGGCAGAUCACUUGAGGU 18

Intron2-2600 17700

CFTR-

+ CGGGCAGAUCACUUGAGGU 19

Intron2-2601 17701

CFTR-

+ GCGGGCAGAUCACUUGAGGU 20

Intron2-2602 17702

CFTR-

+ GGCGGGCAGAUCACUUGAGGU 21

Intron2-2603 17703

CFTR-

+ AGGCGGGCAGAUCACUUGAGGU 22

Intron2-2604 17704

CFTR-

+ AAGGCGGGCAGAUCACUUGAGGU 23

Intron2-2605 17705

CFTR-

+ CAAGGCGGGCAGAUCACUUGAGGU 24

Intron2-2606 17706

CFTR-

+ UGGGCAGAUCACUUGAGGU 19

Intron2-2607 17707

CFTR-

+ GUGGGCAGAUCACUUGAGGU 20

Intron2-2608 17708

CFTR-

+ GGUGGGCAGAUCACUUGAGGU 21

Intron2-2609 17709

CFTR-

+ AGGUGGGCAGAUCACUUGAGGU 22

Intron2-2610 17710

CFTR-

+ AAGGUGGGCAGAUCACUUGAGGU 23

lntron2-2611 17711

CFTR-

+ CAAGGUGGGCAGAUCACUUGAGGU 24

lntron2-2612 17712

CFTR-

+ GUAGAAAGCUGGUCCGGU 18

lntron2-2613 17713

549

5535.1 CFTR-

+ UGUAGAAAGCUGGUCCGGU 19

lntron2-2614 17714

CFTR-

+ AUGUAGAAAGCUGGUCCGGU 20

lntron2-2615 17715

CFTR-

+ UAUGUAGAAAGCUGGUCCGGU 21

lntron2-2616 17716

CFTR-

+ UUAUGUAGAAAGCUGGUCCGGU 22

lntron2-2617 17717

CFTR-

+ UUUAUGUAGAAAGCUGGUCCGGU 23

lntron2-2618 17718

CFTR-

+ CUUUAUGUAGAAAGCUGGUCCGGU 24

lntron2-2619 17719

CFTR-

+ ACCUAUAAUCCCAGCAUU 18

Intron2-2620 17720

CFTR-

+ CACCUAUAAUCCCAGCAUU 19

lntron2-2621 17721

CFTR-

+ ACACCUAUAAUCCCAGCAUU 20

lntron2-2622 17722

CFTR-

+ CACACCUAUAAUCCCAGCAUU 21

lntron2-2623 17723

CFTR-

+ UCACACCUAUAAUCCCAGCAUU 22

lntron2-2624 17724

CFTR-

+ CUCACACCUAUAAUCCCAGCAUU 23

lntron2-2625 17725

CFTR-

+ GCUCACACCUAUAAUCCCAGCAUU 24

lntron2-2626 17726

CFTR-

+ AAUACCCAUUAUAUUAUU 18

lntron2-2627 17727

CFTR-

+ CAAUACCCAUUAUAUUAUU 19

lntron2-2628 17728

CFTR-

+ UCAAUACCCAUUAUAUUAUU 20

lntron2-2629 17729

CFTR-

+ UUCAAUACCCAUUAUAUUAUU 21

Intron2-2630 17730

CFTR-

+ AUUCAAUACCCAUUAUAUUAUU 22

lntron2-2631 17731

CFTR-

+ UAUUCAAUACCCAUUAUAUUAUU 23

lntron2-2632 17732

CFTR-

+ AUAUUCAAUACCCAUUAUAUUAUU 24

lntron2-2633 17733

CFTR-

+ CCACUAAUCCCAACACUU 18

lntron2-2634 17734

550

5535.1 CFTR-

+ GCCACUAAUCCCAACACUU 19

l ntron2-2635 17735

CFTR-

+ CGCCACUAAUCCCAACACUU 20

l ntron2-717 15817

CFTR-

+ ACGCCACUAAUCCCAACACUU 21

lntron2-2636 17736

CFTR-

+ CACGCCACUAAUCCCAACACUU 22

lntron2-2637 17737

CFTR-

+ UCACGCCACUAAUCCCAACACUU 23

lntron2-2638 17738

CFTR-

+ CUCACGCCACUAAUCCCAACACUU 24

lntron2-2639 17739

CFTR-

+ ACCAUCUGGCAACCACU U 18

Intron2-2640 17740

CFTR-

+ AACCAUCUGGCAACCACUU 19

lntron2-2641 17741

CFTR-

+ CAACCAUCUGGCAACCACUU 20

lntron2-2642 17742

CFTR-

+ UCAACCAUCUGGCAACCACUU 21

lntron2-2643 17743

CFTR-

+ UUCAACCAUCUGGCAACCACUU 22

lntron2-2644 17744

CFTR-

+ CUUCAACCAUCUGGCAACCACUU 23

lntron2-2645 17745

CFTR-

+ UCU UCAACCAUCUGGCAACCACUU 24

lntron2-2646 17746

CFTR-

+ AUGGUGGAAACCAUACU U 18

lntron2-2647 17747

CFTR-

+ CAUGGUGGAAACCAUACUU 19

lntron2-2648 17748

CFTR-

+ ACAUGGUGGAAACCAUACUU 20

lntron2-2649 17749

CFTR-

+ AACAUGGUGGAAACCAUACUU 21

Intron2-2650 17750

CFTR-

+ GAACAUGGUGGAAACCAUACUU 22

lntron2-2651 17751

CFTR-

+ GGAACAUGGUGGAAACCAUACUU 23

lntron2-2652 17752

CFTR-

+ AGGAACAUGGUGGAAACCAUACUU 24

lntron2-2653 17753

CFTR-

+ C A U G G U C AC A AG G C AG U U 18

lntron2-2654 17754

551

5535.1 CFTR-

+ CCAUGGUCACAAGGCAGUU 19

lntron2-2655 17755

CFTR-

+ GCCAUGGUCACAAGGCAGUU 20

lntron2-2656 17756

CFTR-

+ GGCCAUGGUCACAAGGCAGUU 21

lntron2-2657 17757

CFTR-

+ GGGCCAUGGUCACAAGGCAGUU 22

lntron2-2658 17758

CFTR-

+ AGGGCCAUGGUCACAAGGCAGUU 23

lntron2-2659 17759

CFTR-

+ GAGGGCCAUGGUCACAAGGCAGUU 24

Intron2-2660 17760

CFTR-

+ UAUUCAAAUAUAAAGGUU 18

lntron2-2661 17761

CFTR-

+ GUAUUCAAAUAUAAAGGUU 19

lntron2-2662 17762

CFTR-

+ UGUAUUCAAAUAUAAAGGUU 20

lntron2-2663 17763

CFTR-

+ UUGUAUUCAAAUAUAAAGGUU 21

lntron2-2664 17764

CFTR-

+ UUUGUAUUCAAAUAUAAAGGUU 22

lntron2-2665 17765

CFTR-

+ AUUUGUAUU CAAAU AU AAAGG U U 23

lntron2-2666 17766

CFTR-

+ CAUUUGUAUUCAAAUAUAAAGGUU 24

lntron2-2667 17767

CFTR-

+ CCUAUAAUCCCAGCAUUU 18

lntron2-2668 17768

CFTR-

+ ACCUAUAAUCCCAGCAUUU 19

lntron2-2669 17769

CFTR-

+ CACCUAUAAUCCCAGCAUUU 20

Intron2-720 15820

CFTR-

+ ACACCUAUAAUCCCAGCAUUU 21

Intron2-2670 17770

CFTR-

+ CACACCUAUAAUCCCAGCAUUU 22

lntron2-2671 17771

CFTR-

+ UCACACCUAUAAUCCCAGCAUUU 23

lntron2-2672 17772

CFTR-

+ CUCACACCUAUAAUCCCAGCAUUU 24

lntron2-2673 17773

CFTR-

+ CACUAAUCCCAACACUUU 18

lntron2-2674 17774 CFTR-

+ CCACU AAU CCCAACACU U U 19

lntron2-2675 17775

CFTR-

+ GCCACUAAUCCCAACACUUU 20

lntron2-476 15576

CFTR-

+ CGCCACUAAUCCCAACACUUU 21

lntron2-2676 17776

CFTR-

+ ACGCCACUAAUCCCAACACUUU 22

lntron2-2677 17777

CFTR-

+ CACGCCACUAAUCCCAACACUUU 23

lntron2-2678 17778

CFTR-

+ U CACGCCACU AAU CCCAACACU U U 24

lntron2-2679 17779

CFTR-

+ GAAACUGAGAGAUUCUUU 18

Intron2-2680 17780

CFTR-

+ GGAAACUGAGAGAUUCUUU 19

lntron2-2681 17781

CFTR-

+ AGGAAACUGAGAGAUUCUUU 20

lntron2-2682 17782

CFTR-

+ AAGGAAACUGAGAGAUUCUUU 21

lntron2-2683 17783

CFTR-

+ AAAGG AAACUG AG AG AU U CU U U 22

lntron2-2684 17784

CFTR-

+ GAAAGGAAACUGAGAGAUUCUUU 23

lntron2-2685 17785

CFTR-

+ GGAAAGGAAACUGAGAGAUUCUUU 24

lntron2-2686 17786

CFTR-

+ CCCUGGGCAAUGUAGUUU 18

lntron2-2687 17787

CFTR-

+ ACCCUGGGCAAUGUAGUUU 19

lntron2-2688 17788

CFTR-

+ GACCCUGGGCAAUGUAGUUU 20

lntron2-2689 17789

CFTR-

+ UGACCCUGGGCAAUGUAGUUU 21

Intron2-2690 17790

CFTR-

+ GUGACCCUGGGCAAUGUAGUUU 22

lntron2-2691 17791

CFTR-

+ AGUGACCCUGGGCAAUGUAGUUU 23

lntron2-2692 17792

CFTR-

+ UAGUGACCCUGGGCAAUGUAGUUU 24

lntron2-2693 17793

CFTR-

+ CUAUAAUCCCAGCAUUUU 18

lntron2-2694 17794 CFTR-

+ CCUAUAAUCCCAGCAUUUU 19

lntron2-2695 17795

CFTR-

+ ACCUAUAAUCCCAGCAUUUU 20

lntron2-722 15822

CFTR-

+ CACCUAUAAUCCCAGCAUUUU 21

lntron2-2696 17796

CFTR-

+ ACACCUAUAAUCCCAGCAUUUU 22

lntron2-2697 17797

CFTR-

+ CACACCUAUAAUCCCAGCAUUUU 23

lntron2-2698 17798

CFTR-

+ UCACACCUAUAAUCCCAGCAUUUU 24

lntron2-2699 17799

CFTR-

+ CCUGGGCAAUGUAGUUUU 18

Intron2-2700 17800

CFTR-

+ CCCUGGGCAAUGUAGUUUU 19

Intron2-2701 17801

CFTR-

+ ACCCUGGGCAAUGUAGUUUU 20

lntron2-416 15516

CFTR-

+ GACCCUGGGCAAUGUAGUUUU 21

Intron2-2702 17802

CFTR-

+ UGACCCUGGGCAAUGUAGUUUU 22

Intron2-2703 17803

CFTR-

+ GUGACCCUGGGCAAUGUAGUUUU 23

Intron2-2704 17804

CFTR-

+ AGUGACCCUGGGCAAUGUAGUUUU 24

Intron2-2705 17805

CFTR-

+ AACCAAAUGUGUAUUUUU 18

Intron2-2706 17806

CFTR-

+ AAACCAAAUGUGUAUUUUU 19

Intron2-2707 17807

CFTR-

+ GAAACCAAAUGUGUAUUUUU 20

Intron2-2708 17808

CFTR-

+ UGAAACCAAAUGUGUAUUUUU 21

Intron2-2709 17809

CFTR-

+ CUGAAACCAAAUGUGUAUUUUU 22

Intron2-2710 17810

CFTR-

+ UCUGAAACCAAAUGUGUAUUUUU 23

lntron2-2711 17811

CFTR-

+ CUCUGAAACCAAAUGUGUAUUUUU 24

lntron2-2712 17812

CFTR-

- AU AG U AU U U AAAAG AAAA 18

lntron2-2713 17813

554

5535.1 CFTR-

- UAUAGUAUU U AAAAG AAAA 19

lntron2-2714 17814

CFTR-

- CUAUAGUAUU U AAAAG AAAA 20

lntron2-2715 17815

CFTR-

- CCUAUAGUAUU U AAAAG AAAA 21

lntron2-2716 17816

CFTR-

- UCCUAUAGUAUU U AAAAG AAAA 22

lntron2-2717 17817

CFTR-

- UUCCUAUAGUAUU U AAAAG AAAA 23

lntron2-2718 17818

CFTR-

- GUUCCUAUAGUAUUUAAAAGAAAA 24

lntron2-2719 17819

CFTR-

- AUUUUACAG AAAAG C A A A 18

Intron2-2720 17820

CFTR-

- U AU U U UACAG AAAAG CAAA 19

lntron2-2721 17821

CFTR-

- CUAUUUUACAG AAAAG C A A A 20

lntron2-2722 17822

CFTR-

- UCUAUUUUACAG AAAAG CAAA 21

lntron2-2723 17823

CFTR-

- CUCUAUUUUACAGAAAAGCAAA 22

lntron2-2724 17824

CFTR-

- UCUCUAUUU U AC AG A A A AG CAAA 23

lntron2-2725 17825

CFTR-

- AUCUCUAUUUUACAGAAAAGCAAA 24

lntron2-2726 17826

CFTR-

- UGAUUUUAGUAGUUGAAA 18

lntron2-2727 17827

CFTR-

- AUGAUUUUAGUAGUUGAAA 19

lntron2-2728 17828

CFTR-

- CAUGAUUUUAGUAGUUGAAA 20

lntron2-2729 17829

CFTR-

- ACAUGAUUUUAGUAGUUGAAA 21

Intron2-2730 17830

CFTR-

- UACAUGAUUUUAGUAGUUGAAA 22

lntron2-2731 17831

CFTR-

- AUACAUGAUUUUAGUAGUUGAAA 23

lntron2-2732 17832

CFTR-

- AAUACAUGAUUUUAGUAGUUGAAA 24

lntron2-2733 17833

CFTR-

- CU AG CU UAAG U AAAU AAA 18

lntron2-2734 17834

555

5535.1 CFTR-

- ACUAGCUUAAGUAAAUAAA 19

lntron2-2735 17835

CFTR-

- UACUAGCUUAAGUAAAUAAA 20

lntron2-613 15713

CFTR-

- UUACUAGCUUAAGUAAAUAAA 21

lntron2-2736 17836

CFTR-

- U U U ACU AG CU UAAG U AAAU AAA 22

lntron2-2737 17837

CFTR-

- AUUUACUAGCUUAAGUAAAUAAA 23

lntron2-2738 17838

CFTR-

- AAUUUACUAGCUUAAGUAAAUAAA 24

lntron2-2739 17839

CFTR-

- CUGGCCUUAGGAACUCAA 18

Intron2-2740 17840

CFTR-

- ACUGGCCUUAGGAACUCAA 19

lntron2-2741 17841

CFTR-

- AACUGGCCUUAGGAACUCAA 20

lntron2-241 15341

CFTR-

- GAACUGGCCUUAGGAACUCAA 21

lntron2-2742 17842

CFTR-

- AGAACUGGCCUUAGGAACUCAA 22

lntron2-2743 17843

CFTR-

- GAGAACUGGCCUUAGGAACUCAA 23

lntron2-2744 17844

CFTR-

- GGAGAACUGGCCUUAGGAACUCAA 24

lntron2-2745 17845

CFTR-

- AUCCCCAAGUGCCUAGAA 18

lntron2-2746 17846

CFTR-

- UAUCCCCAAGUGCCUAGAA 19

lntron2-2747 17847

CFTR-

- GUAUCCCCAAGUGCCUAGAA 20

lntron2-2748 17848

CFTR-

- UGUAUCCCCAAGUGCCUAGAA 21

lntron2-2749 17849

CFTR-

- AUGUAUCCCCAAGUGCCUAGAA 22

Intron2-2750 17850

CFTR-

- GAUGUAUCCCCAAGUGCCUAGAA 23

lntron2-2751 17851

CFTR-

- UGAUGUAUCCCCAAGUGCCUAGAA 24

lntron2-2752 17852

CFTR-

- GAUAAAAGGGUGAGUGAA 18

lntron2-2753 17853

556

5535.1 CFTR-

- AGAUAAAAGGGUGAGUGAA 19

lntron2-2754 17854

CFTR-

- CAGAUAAAAGGGUGAGUGAA 20

lntron2-248 15348

CFTR-

- CCAGAUAAAAGGGUGAGUGAA 21

lntron2-2755 17855

CFTR-

- GCCAGAUAAAAGGGUGAGUGAA 22

lntron2-2756 17856

CFTR-

- UGCCAGAUAAAAGGGUGAGUGAA 23

lntron2-2757 17857

CFTR-

- AUGCCAGAUAAAAGGGUGAGUGAA 24

lntron2-2758 17858

CFTR-

- AUUUUAUUCCUUUGUGAA 18

lntron2-2759 17859

CFTR-

- UAUUUUAUUCCUUUGUGAA 19

Intron2-2760 17860

CFTR-

- AUAUUUUAUUCCUUUGUGAA 20

lntron2-2761 17861

CFTR-

- GAUAUUUUAUUCCUUUGUGAA 21

lntron2-2762 17862

CFTR-

- AGAUAUUUUAUUCCUUUGUGAA 22

lntron2-2763 17863

CFTR-

- GAGAUAUUUUAUUCCUUUGUGAA 23

lntron2-2764 17864

CFTR-

- AGAGAUAUUUUAUUCCUUUGUGAA 24

lntron2-2765 17865

CFTR-

- ACU AG CU UAAG UAAAUAA 18

lntron2-2766 17866

CFTR-

- UACUAGCUUAAGUAAAUAA 19

lntron2-2767 17867

CFTR-

- U U ACU AG CU UAAG UAAAUAA 20

lntron2-2768 17868

CFTR-

- U U U ACU AG CU UAAG UAAAUAA 21

lntron2-2769 17869

CFTR-

- AUUUACUAGCU UAAG UAAAUAA 22

Intron2-2770 17870

CFTR-

- AAU U U ACU AG CU UAAG UAAAUAA 23

lntron2-2771 17871

CFTR-

- CAAUUUACUAGCUUAAGUAAAUAA 24

lntron2-2772 17872

CFTR-

- UGUCUAUUCUUACUAUAA 18

lntron2-2773 17873

557

5535.1 CFTR-

- AUGUCUAUUCUUACUAUAA 19

lntron2-2774 17874

CFTR-

- AAUGUCUAUUCUUACUAUAA 20

lntron2-2775 17875

CFTR-

- UAAUGUCUAUUCUUACUAUAA 21

lntron2-2776 17876

CFTR-

- UUAAUGUCUAUUCUUACUAUAA 22

lntron2-2777 17877

CFTR-

- UUUAAUGUCUAUUCUUACUAUAA 23

lntron2-2778 17878

CFTR-

- AUUUAAUGUCUAUUCUUACUAUAA 24

lntron2-2779 17879

CFTR-

- AUGGUAACUUGACAGUAA 18

Intron2-2780 17880

CFTR-

- UAUGGUAACUUGACAGUAA 19

lntron2-2781 17881

CFTR-

- UUAUGGUAACUUGACAGUAA 20

lntron2-251 15351

CFTR-

- CUUAUGGUAACUUGACAGUAA 21

lntron2-2782 17882

CFTR-

- ACUUAUGGUAACUUGACAGUAA 22

lntron2-2783 17883

CFTR-

- UACUUAUGGUAACUUGACAGUAA 23

lntron2-2784 17884

CFTR-

- UUACUUAUGGUAACUUGACAGUAA 24

lntron2-2785 17885

CFTR-

- AAAAAAGG CUUU CAU UAA 18

lntron2-2786 17886

CFTR-

- G A A A A A AG GCUUUCAUUAA 19

lntron2-2787 17887

CFTR-

- AGAAAAAAGGCUUUCAUUAA 20

lntron2-2788 17888

CFTR-

- GAGAAAAAAGGCUUUCAUUAA 21

lntron2-2789 17889

CFTR-

- AG AG AAAAAAGG CU U U CAU UAA 22

Intron2-2790 17890

CFTR-

- AAG AG A A A A A AG GCUUUCAUUAA 23

lntron2-2791 17891

CFTR-

- G AAG AG AAAAAAGG CU U U CAU UAA 24

lntron2-2792 17892

CFTR-

- AGAGUAGGGCUGGGUUAA 18

lntron2-2793 17893

558

5535.1 CFTR-

- CAGAGUAGGGCUGGGUUAA 19

lntron2-2794 17894

CFTR-

- UCAGAGUAGGGCUGGGUUAA 20

lntron2-2795 17895

CFTR-

- AUCAGAGUAGGGCUGGGUUAA 21

lntron2-2796 17896

CFTR-

- AAUCAGAGUAGGGCUGGGUUAA 22

lntron2-2797 17897

CFTR-

- UAAUCAGAGUAGGGCUGGGUUAA 23

lntron2-2798 17898

CFTR-

- UUAAUCAGAGUAGGGCUGGGUUAA 24

lntron2-2799 17899

CFTR-

- UGUUCCUAUAGUAUUUAA 18

Intron2-2800 17900

CFTR-

- GUGUUCCUAUAGUAUUUAA 19

Intron2-2801 17901

CFTR-

- GGUGUUCCUAUAGUAUUUAA 20

Intron2-2802 17902

CFTR-

- UGGUGUUCCUAUAGUAUUUAA 21

Intron2-2803 17903

CFTR-

- CUGGUGUUCCUAUAGUAUUUAA 22

Intron2-2804 17904

CFTR-

- GCUGGUGUUCCUAUAGUAUUUAA 23

Intron2-2805 17905

CFTR-

- AGCUGGUGUUCCUAUAGUAUUUAA 24

Intron2-2806 17906

CFTR-

- GUGGACCACUUUUUCACA 18

Intron2-2807 17907

CFTR-

- UGUGGACCACUUUUUCACA 19

Intron2-2808 17908

CFTR-

- GUGUGGACCACUUUUUCACA 20

Intron2-2809 17909

CFTR-

- CGUGUGGACCACUUUUUCACA 21

Intron2-2810 17910

CFTR-

- CCGUGUGGACCACUUUUUCACA 22

lntron2-2811 17911

CFTR-

- UCCGUGUGGACCACUUUUUCACA 23

lntron2-2812 17912

CFTR-

- UUCCGUGUGGACCACUUUUUCACA 24

lntron2-2813 17913

CFTR-

- GAAAUGGCUAGCAUUACA 18

lntron2-2814 17914

559

5535.1 CFTR-

- UGAAAUGGCUAGCAUUACA 19

lntron2-2815 17915

CFTR-

- GUGAAAUGGCUAGCAUUACA 20

lntron2-2816 17916

CFTR-

- UGUGAAAUGGCUAGCAUUACA 21

lntron2-2817 17917

CFTR-

- AUGUGAAAUGGCUAGCAUUACA 22

lntron2-2818 17918

CFTR-

- AAUGUGAAAUGGCUAGCAUUACA 23

lntron2-2819 17919

CFTR-

- GAAUGUGAAAUGGCUAGCAUUACA 24

Intron2-2820 17920

CFTR-

- ACUGGCCUUAGGAACUCA 18

lntron2-2821 17921

CFTR-

- AACUGGCCUUAGGAACUCA 19

lntron2-2822 17922

CFTR-

- GAACUGGCCUUAGGAACUCA 20

lntron2-2823 17923

CFTR-

- AGAACUGGCCUUAGGAACUCA 21

lntron2-2824 17924

CFTR-

- GAGAACUGGCCUUAGGAACUCA 22

lntron2-2825 17925

CFTR-

- GGAGAACUGGCCUUAGGAACUCA 23

lntron2-2826 17926

CFTR-

- UGGAGAACUGGCCUUAGGAACUCA 24

lntron2-2827 17927

CFTR-

- AAAG CAAAC U G AG G C U C A 18

lntron2-2828 17928

CFTR-

- A A A AG C A A AC U G AG G C U C A 19

lntron2-2829 17929

CFTR-

- GAAAAGCAAACUGAGGCUCA 20

Intron2-2830 17930

CFTR-

- AG AAAAG CAAAC U GAG G C U CA 21

lntron2-2831 17931

CFTR-

- CAGAAAAG CAAAC U GAG G C U CA 22

lntron2-2832 17932

CFTR-

- ACAGAAAAGCAAACUGAGGCUCA 23

lntron2-2833 17933

CFTR-

- UACAGAAAAGCAAACUGAGGCUCA 24

lntron2-2834 17934

CFTR-

- U U U AAGG ACCACG AAAG A 18

lntron2-2835 17935

560

5535.1 CFTR-

- CU U U AAGG ACCACG AAAG A 19

lntron2-2836 17936

CFTR-

- UCUUUAAGGACCACGAAAGA 20

lntron2-274 15374

CFTR-

- AUCUUUAAGGACCACGAAAGA 21

lntron2-2837 17937

CFTR-

- UAUCUUUAAGGACCACGAAAGA 22

lntron2-2838 17938

CFTR-

- CUAUCUUUAAGGACCACGAAAGA 23

lntron2-2839 17939

CFTR-

- CCUAUCUUUAAGGACCACGAAAGA 24

Intron2-2840 17940

CFTR-

- UUUGUAUUUAUGGCCAGA 18

lntron2-2841 17941

CFTR-

- AUUUGUAUUUAUGGCCAGA 19

lntron2-2842 17942

CFTR-

- CAUUUGUAUUUAUGGCCAGA 20

lntron2-2843 17943

CFTR-

- ACAUUUGUAUUUAUGGCCAGA 21

lntron2-2844 17944

CFTR-

- UACAUUUGUAUUUAUGGCCAGA 22

lntron2-2845 17945

CFTR-

- AUACAUUUGUAUUUAUGGCCAGA 23

lntron2-2846 17946

CFTR-

- GAUACAUUUGUAUUUAUGGCCAGA 24

lntron2-2847 17947

CFTR-

- UGGUUUUAUUUUCUCAGA 18

lntron2-2848 17948

CFTR-

- CUGGUUUUAUUUUCUCAGA 19

lntron2-2849 17949

CFTR-

- GCUGGUUUUAUUUUCUCAGA 20

Intron2-2850 17950

CFTR-

- UGCUGGUUUUAUUUUCUCAGA 21

lntron2-2851 17951

CFTR-

- AUGCUGGUUUUAUUUUCUCAGA 22

lntron2-2852 17952

CFTR-

- UAUGCUGGUUUUAUUUUCUCAGA 23

lntron2-2853 17953

CFTR-

- UUAUGCUGGUUUUAUUUUCUCAGA 24

lntron2-2854 17954

CFTR-

- UGUGGGGAGGGAAAUAGA 18

lntron2-2855 17955

561

5535.1 CFTR-

- AUGUGGGGAGGGAAAUAGA 19

lntron2-2856 17956

CFTR-

- CAUGUGGGGAGGGAAAUAGA 20

lntron2-278 15378

CFTR-

- GCAUGUGGGGAGGGAAAUAGA 21

lntron2-2857 17957

CFTR-

- AGCAUGUGGGGAGGGAAAUAGA 22

lntron2-2858 17958

CFTR-

- AAGCAUGUGGGGAGGGAAAUAGA 23

lntron2-2859 17959

CFTR-

- GAAGCAUGUGGGGAGGGAAAUAGA 24

Intron2-2860 17960

CFTR-

- GGCCACUCAUAGUCUAGA 18

lntron2-2861 17961

CFTR-

- GGGCCACUCAUAGUCUAGA 19

lntron2-2862 17962

CFTR-

- UGGGCCACUCAUAGUCUAGA 20

lntron2-2863 17963

CFTR-

- UUGGGCCACUCAUAGUCUAGA 21

lntron2-2864 17964

CFTR-

- CUUGGGCCACUCAUAGUCUAGA 22

lntron2-2865 17965

CFTR-

- CCUUGGGCCACUCAUAGUCUAGA 23

lntron2-2866 17966

CFTR-

- CCCUUGGGCCACUCAUAGUCUAGA 24

lntron2-2867 17967

CFTR-

- UAUCUUUAAGGACCACGA 18

lntron2-2868 17968

CFTR-

- CUAUCUUUAAGGACCACGA 19

lntron2-2869 17969

CFTR-

- CCUAUCUUUAAGGACCACGA 20

Intron2-2870 17970

CFTR-

- UCCUAUCUUUAAGGACCACGA 21

lntron2-2871 17971

CFTR-

- CUCCUAUCUUUAAGGACCACGA 22

lntron2-2872 17972

CFTR-

- GCUCCUAUCUUUAAGGACCACGA 23

lntron2-2873 17973

CFTR-

- UGCUCCUAUCUUUAAGGACCACGA 24

lntron2-2874 17974

CFTR-

- UGGAGAAGCAUGUGGGGA 18

lntron2-2875 17975

562

5535.1 CFTR-

- GUGGAGAAGCAUGUGGGGA 19

lntron2-2876 17976

CFTR-

- GGUGGAGAAGCAUGUGGGGA 20

lntron2-53 15153

CFTR-

- AGGUGGAGAAGCAUGUGGGGA 21

lntron2-2877 17977

CFTR-

- AAGGUGGAGAAGCAUGUGGGGA 22

lntron2-2878 17978

CFTR-

- AAAGGUGGAGAAGCAUGUGGGGA 23

lntron2-2879 17979

CFTR-

- GAAAGGUGGAGAAGCAUGUGGGGA 24

Intron2-2880 17980

CFTR-

- GUAACCAAAUGUUAUGGA 18

lntron2-2881 17981

CFTR-

- AGUAACCAAAUGUUAUGGA 19

lntron2-2882 17982

CFTR-

- GAGUAACCAAAUGUUAUGGA 20

lntron2-54 15154

CFTR-

- UGAGUAACCAAAUGUUAUGGA 21

lntron2-2883 17983

CFTR-

- CUGAGUAACCAAAUGUUAUGGA 22

lntron2-2884 17984

CFTR-

- UCUGAGUAACCAAAUGUUAUGGA 23

lntron2-2885 17985

CFTR-

- CUCUGAGUAACCAAAUGUUAUGGA 24

lntron2-2886 17986

CFTR-

- UUGCCAGUUAAUGAAUGA 18

lntron2-2887 17987

CFTR-

- UUUGCCAGUUAAUGAAUGA 19

lntron2-2888 17988

CFTR-

- CUUUGCCAGUUAAUGAAUGA 20

lntron2-281 15381

CFTR-

- ACUUUGCCAGUUAAUGAAUGA 21

lntron2-2889 17989

CFTR-

- UACUUUGCCAGUUAAUGAAUGA 22

Intron2-2890 17990

CFTR-

- AUACUUUGCCAGUUAAUGAAUGA 23

lntron2-2891 17991

CFTR-

- UAUACUUUGCCAGUUAAUGAAUGA 24

lntron2-2892 17992

CFTR-

- UCCUCUCAGCCACUCUGA 18

lntron2-2893 17993

563

5535.1 CFTR-

- CUCCUCUCAGCCACUCUGA 19

lntron2-2894 17994

CFTR-

- UCUCCUCUCAGCCACUCUGA 20

lntron2-2895 17995

CFTR-

- AUCUCCUCUCAGCCACUCUGA 21

lntron2-2896 17996

CFTR-

- UAUCUCCUCUCAGCCACUCUGA 22

lntron2-2897 17997

CFTR-

- AUAUCUCCUCUCAGCCACUCUGA 23

lntron2-2898 17998

CFTR-

- AAUAUCUCCUCUCAGCCACUCUGA 24

lntron2-2899 17999

CFTR-

- CCUUUUGAUUGCCAGUGA 18

Intron2-2900 18000

CFTR-

- UCCUUUUGAUUGCCAGUGA 19

Intron2-2901 18001

CFTR-

- AUCCUUUUGAUUGCCAGUGA 20

Intron2-2902 18002

CFTR-

- GAUCCUUUUGAUUGCCAGUGA 21

Intron2-2903 18003

CFTR-

- GGAUCCUUUUGAUUGCCAGUGA 22

Intron2-2904 18004

CFTR-

- AGGAUCCUUUUGAUUGCCAGUGA 23

Intron2-2905 18005

CFTR-

- UAGGAUCCUUUUGAUUGCCAGUGA 24

Intron2-2906 18006

CFTR-

- AGAUAAAAGGGUGAGUGA 18

Intron2-2907 18007

CFTR-

- CAGAUAAAAGGGUGAGUGA 19

Intron2-2908 18008

CFTR-

- CCAGAUAAAAGGGUGAGUGA 20

lntron2-283 15383

CFTR-

- GCCAGAUAAAAGGGUGAGUGA 21

Intron2-2909 18009

CFTR-

- UGCCAGAUAAAAGGGUGAGUGA 22

Intron2-2910 18010

CFTR-

- AUGCCAGAUAAAAGGGUGAGUGA 23

lntron2-2911 18011

CFTR-

- GAUGCCAGAUAAAAGGGUGAGUGA 24

lntron2-2912 18012

CFTR-

- UGCCAGAUAAAAGGGUGA 18

lntron2-2913 18013

564

5535.1 CFTR-

- AUGCCAGAUAAAAGGGUGA 19

lntron2-2914 18014

CFTR-

- GAUGCCAGAUAAAAGGGUGA 20

lntron2-2915 18015

CFTR-

- UGAUGCCAGAUAAAAGGGUGA 21

lntron2-2916 18016

CFTR-

- CUGAUGCCAGAUAAAAGGGUGA 22

lntron2-2917 18017

CFTR-

- CCUGAUGCCAGAUAAAAGGGUGA 23

lntron2-2918 18018

CFTR-

- GCCUGAUGCCAGAUAAAAGGGUGA 24

lntron2-2919 18019

CFTR-

- GGUUAGCUCUGUGUGUGA 18

Intron2-2920 18020

CFTR-

- AGGUUAGCUCUGUGUGUGA 19

lntron2-2921 18021

CFTR-

- GAGGUUAGCUCUGUGUGUGA 20

lntron2-2922 18022

CFTR-

- GGAGGUUAGCUCUGUGUGUGA 21

lntron2-2923 18023

CFTR-

- GGGAGGUUAGCUCUGUGUGUGA 22

lntron2-2924 18024

CFTR-

- UGGGAGGUUAGCUCUGUGUGUGA 23

lntron2-2925 18025

CFTR-

- AUGGGAGGUUAGCUCUGUGUGUGA 24

lntron2-2926 18026

CFTR-

- GAUCCAUUUCUCCUUUGA 18

lntron2-2927 18027

CFTR-

- UGAUCCAUUUCUCCUUUGA 19

lntron2-2928 18028

CFTR-

- CUGAUCCAUUUCUCCUUUGA 20

lntron2-285 15385

CFTR-

- UCUGAUCCAUUUCUCCUUUGA 21

lntron2-2929 18029

CFTR-

- AUCUGAUCCAUUUCUCCUUUGA 22

Intron2-2930 18030

CFTR-

- CAUCUGAUCCAUUUCUCCUUUGA 23

lntron2-2931 18031

CFTR-

- CCAUCUGAUCCAUUUCUCCUUUGA 24

lntron2-2932 18032

CFTR-

- UGUAUUUAUGGCCAGAUA 18

lntron2-2933 18033

565

5535.1 CFTR-

- UUGUAUUUAUGGCCAGAUA 19

lntron2-2934 18034

CFTR-

- UUUGUAUUUAUGGCCAGAUA 20

lntron2-2935 18035

CFTR-

- AUUUGUAUUUAUGGCCAGAUA 21

lntron2-2936 18036

CFTR-

- CAUUUGUAUUUAUGGCCAGAUA 22

lntron2-2937 18037

CFTR-

- ACAUUUGUAUUUAUGGCCAGAUA 23

lntron2-2938 18038

CFTR-

- UACAUUUGUAUUUAUGGCCAGAUA 24

lntron2-2939 18039

CFTR-

- AUUCAAAGAAUUAAGCUA 18

Intron2-2940 18040

CFTR-

- UAUUCAAAGAAUUAAGCUA 19

lntron2-2941 18041

CFTR-

- UUAUUCAAAGAAUUAAGCUA 20

lntron2-2942 18042

CFTR-

- UU UAUUCAAAGAAUUAAGCUA 21

lntron2-2943 18043

CFTR-

- U U U U AU U CAAAG AAU U AAG CU A 22

lntron2-2944 18044

CFTR-

- AUUUUAUUCAAAGAAUUAAGCUA 23

lntron2-2945 18045

CFTR-

- GAUUUUAUU CAAAG AAU U AAG CU A 24

lntron2-2946 18046

CFTR-

- UAUGGUAACUUGACAGUA 18

lntron2-2947 18047

CFTR-

- UUAUGGUAACUUGACAGUA 19

lntron2-2948 18048

CFTR-

- CUUAUGGUAACUUGACAGUA 20

lntron2-2949 18049

CFTR-

- ACU UAUGGUAACUUGACAGUA 21

Intron2-2950 18050

CFTR-

- UACUUAUGGUAACUUGACAGUA 22

lntron2-2951 18051

CFTR-

- UUACUUAUGGUAACUUGACAGUA 23

lntron2-2952 18052

CFTR-

- UUUACUUAUGGUAACUUGACAGUA 24

lntron2-2953 18053

CFTR-

- U U CAAG U U U CACCCAU U A 18

lntron2-2954 18054

566

5535.1 CFTR-

- GUUCAAGUUUCACCCAUUA 19

lntron2-2955 18055

CFTR-

- UGUUCAAGUUUCACCCAUUA 20

lntron2-2956 18056

CFTR-

- UUGUUCAAGUUUCACCCAUUA 21

lntron2-2957 18057

CFTR-

- GUUGUUCAAGUUUCACCCAUUA 22

lntron2-2958 18058

CFTR-

- AGUUGUUCAAGUUUCACCCAUUA 23

lntron2-2959 18059

CFTR-

- AAGUUGUUCAAGUUUCACCCAUUA 24

Intron2-2960 18060

CFTR-

- AAGGGCCAGCUUCUAUUA 18

lntron2-2961 18061

CFTR-

- CAAGGGCCAGCUUCUAUUA 19

lntron2-2962 18062

CFTR-

- UCAAGGGCCAGCUUCUAUUA 20

lntron2-2963 18063

CFTR-

- AUCAAGGGCCAGCUUCUAUUA 21

lntron2-2964 18064

CFTR-

- GAUCAAGGGCCAGCUUCUAUUA 22

lntron2-2965 18065

CFTR-

- AGAUCAAGGGCCAGCUUCUAUUA 23

lntron2-2966 18066

CFTR-

- AAGAUCAAGGGCCAGCUUCUAUUA 24

lntron2-2967 18067

CFTR-

- AUUGGUAUUUGAAAUUUA 18

lntron2-2968 18068

CFTR-

- AAUUGGUAUUUGAAAUUUA 19

lntron2-2969 18069

CFTR-

- AAAUUGGUAUUUGAAAUUUA 20

Intron2-2970 18070

CFTR-

- AAAAUUGGUAUUUGAAAUUUA 21

lntron2-2971 18071

CFTR-

- UAAAAUUGGUAUUUGAAAUUUA 22

lntron2-2972 18072

CFTR-

- AUAAAAUUGGUAUUUGAAAUUUA 23

lntron2-2973 18073

CFTR-

- U AU AAAAU UGG U AU U U G AAAU U U A 24

lntron2-2974 18074

CFTR-

- AAAGGUAAUUAGGCUUUA 18

lntron2-2975 18075

567

5535.1 CFTR-

- AAAAGGUAAUUAGGCUUUA 19

lntron2-2976 18076

CFTR-

- GAAAAGGUAAUUAGGCUUUA 20

lntron2-2977 18077

CFTR-

- GGAAAAGG UAAUUAGGCUUUA 21

lntron2-2978 18078

CFTR-

- GGGAAAAGGUAAUUAGGCUUUA 22

lntron2-2979 18079

CFTR-

- UGGGAAAAGGUAAUUAGGCUUUA 23

Intron2-2980 18080

CFTR-

- AUGGGAAAAGGUAAUUAGGCUUUA 24

lntron2-2981 18081

CFTR-

- AUCAUUAUCUCUAUUUUA 18

lntron2-2982 18082

CFTR-

- CAUCAUUAUCUCUAUUUUA 19

lntron2-2983 18083

CFTR-

- GCAUCAUUAUCUCUAUUUUA 20

lntron2-2984 18084

CFTR-

- AGCAUCAUUAUCUCUAUUUUA 21

lntron2-2985 18085

CFTR-

- AAGCAUCAUUAUCUCUAUUUUA 22

lntron2-2986 18086

CFTR-

- AAAGCAUCAUUAUCUCUAUUUUA 23

lntron2-2987 18087

CFTR-

- GAAAGCAUCAUUAUCUCUAUUUUA 24

lntron2-2988 18088

CFTR-

- UACAUUGCCCAGGGUCAC 18

lntron2-2989 18089

CFTR-

- CUACAUUGCCCAGGGUCAC 19

Intron2-2990 18090

CFTR-

- ACUACAUUGCCCAGGGUCAC 20

lntron2-2991 18091

CFTR-

- AACUACAUUGCCCAGGGUCAC 21

lntron2-2992 18092

CFTR-

- AAACUACAUUGCCCAGGGUCAC 22

lntron2-2993 18093

CFTR-

- AAAACUACAUUGCCCAGGGUCAC 23

lntron2-2994 18094

CFTR-

- UAAAACUACAUUGCCCAGGGUCAC 24

lntron2-2995 18095

CFTR-

- CCUGGUAUGUGGUCCUAC 18

lntron2-2996 18096

568

5535.1 CFTR-

- GCCUGGUAUGUGGUCCUAC 19

lntron2-2997 18097

CFTR-

- GGCCUGGUAUGUGGUCCUAC 20

lntron2-2998 18098

CFTR-

- GGGCCUGGUAUGUGGUCCUAC 21

lntron2-2999 18099

CFTR-

- UGGGCCUGGUAUGUGGUCCUAC 22

Intron2-3000 18100

CFTR-

- CUGGGCCUGGUAUGUGGUCCUAC 23

Intron2-3001 18101

CFTR-

- UCUGGGCCUGGUAUGUGGUCCUAC 24

Intron2-3002 18102

CFTR-

- UUUGUCUUAUUAGAGACC 18

Intron2-3003 18103

CFTR-

- AUUUGUCUUAUUAGAGACC 19

Intron2-3004 18104

CFTR-

- AAUUUGUCUUAUUAGAGACC 20

Intron2-3005 18105

CFTR-

- GAAUUUGUCUUAUUAGAGACC 21

Intron2-3006 18106

CFTR-

- AGAAUUUGUCUUAUUAGAGACC 22

Intron2-3007 18107

CFTR-

- GAGAAUUUGUCUUAUUAGAGACC 23

Intron2-3008 18108

CFTR-

- AGAGAAUUUGUCUUAUUAGAGACC 24

Intron2-3009 18109

CFTR-

- CUCCUAUCUUUAAGGACC 18

Intron2-3010 18110

CFTR-

- GCUCCUAUCUUUAAGGACC 19

Intron2-3011 18111

CFTR-

- UGCUCCUAUCUUUAAGGACC 20

Intron2-3012 18112

CFTR-

- UUGCUCCUAUCUUUAAGGACC 21

Intron2-3013 18113

CFTR-

- UUUGCUCCUAUCUUUAAGGACC 22

Intron2-3014 18114

CFTR-

- CUUUGCUCCUAUCUUUAAGGACC 23

Intron2-3015 18115

CFTR-

- UCUUUGCUCCUAUCUUUAAGGACC 24

Intron2-3016 18116

CFTR-

- UAGGAACUCAAUGGGACC 18

Intron2-3017 18117

569

5535.1 CFTR-

- UUAGGAACUCAAUGGGACC 19

Intron2-3018 18118

CFTR-

- CUUAGGAACUCAAUGGGACC 20

Intron2-3019 18119

CFTR-

- CCUUAGGAACUCAAUGGGACC 21

Intron2-3020 18120

CFTR-

- GCCUUAGGAACUCAAUGGGACC 22

Intron2-3021 18121

CFTR-

- GGCCUUAGGAACUCAAUGGGACC 23

Intron2-3022 18122

CFTR-

- UGGCCUUAGGAACUCAAUGGGACC 24

Intron2-3023 18123

CFTR-

- CUUUGUACCUCUGCACCC 18

Intron2-3024 18124

CFTR-

- ACUUUGUACCUCUGCACCC 19

Intron2-3025 18125

CFTR-

- UACUUUGUACCUCUGCACCC 20

Intron2-3026 18126

CFTR-

- GUACUUUGUACCUCUGCACCC 21

Intron2-3027 18127

CFTR-

- GGUACUUUGUACCUCUGCACCC 22

Intron2-3028 18128

CFTR-

- UGGUACUUUGUACCUCUGCACCC 23

Intron2-3029 18129

CFTR-

- UUGGUACUUUGUACCUCUGCACCC 24

Intron2-3030 18130

CFTR-

- AGUCAUAGUGCUUACCCC 18

Intron2-3031 18131

CFTR-

- GAGUCAUAGUGCUUACCCC 19

Intron2-3032 18132

CFTR-

- UGAGUCAUAGUGCUUACCCC 20

Intron2-3033 18133

CFTR-

- UUGAGUCAUAGUGCUUACCCC 21

Intron2-3034 18134

CFTR-

- CUUGAGUCAUAGUGCUUACCCC 22

Intron2-3035 18135

CFTR-

- UCUUGAGUCAUAGUGCUUACCCC 23

Intron2-3036 18136

CFTR-

- CUCUUGAGUCAUAGUGCUUACCCC 24

Intron2-3037 18137

CFTR-

- GAAUACAAAUGUACUCCC 18

Intron2-3038 18138

570

5535.1 CFTR-

- UGAAUACAAAUGUACUCCC 19

Intron2-3039 18139

CFTR-

- UUGAAUACAAAUGUACUCCC 20

lntron2-312 15412

CFTR-

- UUUGAAUACAAAUGUACUCCC 21

Intron2-3040 18140

CFTR-

- AUUUGAAUACAAAUGUACUCCC 22

Intron2-3041 18141

CFTR-

- UAUUUGAAUACAAAUGUACUCCC 23

Intron2-3042 18142

CFTR-

- AUAUUUGAAUACAAAUGUACUCCC 24

Intron2-3043 18143

CFTR-

- UUGGUGUGUGCAAAUGCC 18

Intron2-3044 18144

CFTR-

- CUUGGUGUGUGCAAAUGCC 19

Intron2-3045 18145

CFTR-

- ACUUGGUGUGUGCAAAUGCC 20

Intron2-3046 18146

CFTR-

- CACUUGGUGUGUGCAAAUGCC 21

Intron2-3047 18147

CFTR-

- ACACUUGGUGUGUGCAAAUGCC 22

Intron2-3048 18148

CFTR-

- AACACUUGGUGUGUGCAAAUGCC 23

Intron2-3049 18149

CFTR-

- GAACACUUGGUGUGUGCAAAUGCC 24

Intron2-3050 18150

CFTR-

- GCUAAAUGUGAAAAAUCC 18

Intron2-3051 18151

CFTR-

- GGCUAAAUGUGAAAAAUCC 19

Intron2-3052 18152

CFTR-

- UGGCUAAAUGUGAAAAAUCC 20

Intron2-3053 18153

CFTR-

- UUGGCUAAAUGUGAAAAAUCC 21

Intron2-3054 18154

CFTR-

- CUUGGCUAAAUGUGAAAAAUCC 22

Intron2-3055 18155

CFTR-

- CCUUGGCUAAAUGUGAAAAAUCC 23

Intron2-3056 18156

CFTR-

- UCCUUGGCUAAAUGUGAAAAAUCC 24

Intron2-3057 18157

CFTR-

- UGAAUACAAAUGUACUCC 18

Intron2-3058 18158

571

5535.1 CFTR-

- UUGAAUACAAAUGUACUCC 19

Intron2-3059 18159

CFTR-

- UUUGAAUACAAAUGUACUCC 20

Intron2-3060 18160

CFTR-

- AUUUGAAUACAAAUGUACUCC 21

Intron2-3061 18161

CFTR-

- UAUUUGAAUACAAAUGUACUCC 22

Intron2-3062 18162

CFTR-

- AUAUUUGAAUACAAAUGUACUCC 23

Intron2-3063 18163

CFTR-

- UAUAUUUGAAUACAAAUGUACUCC 24

Intron2-3064 18164

CFTR-

- UUUAUUGGCUCAUGAAGC 18

Intron2-3065 18165

CFTR-

- AUUUAUUGGCUCAUGAAGC 19

Intron2-3066 18166

CFTR-

- AAUUUAUUGGCUCAUGAAGC 20

Intron2-3067 18167

CFTR-

- GAAUUUAUUGGCUCAUGAAGC 21

Intron2-3068 18168

CFTR-

- CGAAUUUAUUGGCUCAUGAAGC 22

Intron2-3069 18169

CFTR-

- ACGAAUUUAUUGGCUCAUGAAGC 23

Intron2-3070 18170

CFTR-

- AACGAAUUUAUUGGCUCAUGAAGC 24

Intron2-3071 18171

CFTR-

- CUCAGUCUCCUGAGUAGC 18

Intron2-3072 18172

CFTR-

- UCUCAGUCUCCUGAGUAGC 19

Intron2-3073 18173

CFTR-

- AUCUCAGUCUCCUGAGUAGC 20

lntron2-656 15756

CFTR-

- AAUCUCAGUCUCCUGAGUAGC 21

Intron2-3074 18174

CFTR-

- GAAUCUCAGUCUCCUGAGUAGC 22

Intron2-3075 18175

CFTR-

- CGAAUCUCAGUCUCCUGAGUAGC 23

Intron2-3076 18176

CFTR-

- GCGAAUCUCAGUCUCCUGAGUAGC 24

Intron2-3077 18177

CFTR-

- AGUGUUGGGAUUAGUGGC 18

Intron2-3078 18178

572

5535.1 CFTR-

- AAGUGUUGGGAUUAGUGGC 19

Intron2-3079 18179

CFTR-

- AAAGUGUUGGGAUUAGUGGC 20

Intron2-3080 18180

CFTR-

- CAAAGUGUUGGGAUUAGUGGC 21

Intron2-3081 18181

CFTR-

- CCAAAGUGUUGGGAUUAGUGGC 22

Intron2-3082 18182

CFTR-

- CCCAAAGUGUUGGGAUUAGUGGC 23

Intron2-3083 18183

CFTR-

- UCCCAAAGUGUUGGGAUUAGUGGC 24

Intron2-3084 18184

CFTR-

- AGAAACCUGUAGCAUUGC 18

Intron2-3085 18185

CFTR-

- UAGAAACCUGUAGCAUUGC 19

Intron2-3086 18186

CFTR-

- AUAGAAACCUGUAGCAUUGC 20

lntron2-325 15425

CFTR-

- CAU AGAAACCUGUAGCAUUGC 21

Intron2-3087 18187

CFTR-

- ACAUAGAAACCUGUAGCAUUGC 22

Intron2-3088 18188

CFTR-

- UACAUAGAAACCUGUAGCAUUGC 23

Intron2-3089 18189

CFTR-

- UUACAUAGAAACCUGUAGCAUUGC 24

Intron2-3090 18190

CFTR-

- AUUCACACUUCUAAGAUC 18

Intron2-3091 18191

CFTR-

- GAUUCACACUUCUAAGAUC 19

Intron2-3092 18192

CFTR-

- AGAUUCACACUUCUAAGAUC 20

Intron2-3093 18193

CFTR-

- CAGAUUCACACUUCUAAGAUC 21

Intron2-3094 18194

CFTR-

- GCAGAUUCACACUUCUAAGAUC 22

Intron2-3095 18195

CFTR-

- AGCAGAUUCACACUUCUAAGAUC 23

Intron2-3096 18196

CFTR-

- UAGCAGAUUCACACUUCUAAGAUC 24

Intron2-3097 18197

CFTR-

- UCAUUUACAUCUCAGCUC 18

Intron2-3098 18198

573

5535.1 CFTR-

- UUCAUUUACAUCUCAGCUC 19

Intron2-3099 18199

CFTR-

- UUUCAUUUACAUCUCAGCUC 20

Intron2-3100 18200

CFTR-

- CUUUCAUUUACAUCUCAGCUC 21

Intron2-3101 18201

CFTR-

- ACUUUCAUUUACAUCUCAGCUC 22

Intron2-3102 18202

CFTR-

- CACUUUCAUUUACAUCUCAGCUC 23

Intron2-3103 18203

CFTR-

- UCACUUUCAUUUACAUCUCAGCUC 24

Intron2-3104 18204

CFTR-

- GAACGAAUUUAUUGGCUC 18

Intron2-3105 18205

CFTR-

- GGAACGAAUUUAUUGGCUC 19

Intron2-3106 18206

CFTR-

- AGGAACGAAUUUAUUGGCUC 20

Intron2-3107 18207

CFTR-

- AAGGAACGAAUUUAUUGGCUC 21

Intron2-3108 18208

CFTR-

- AAAGGAACGAAUUUAUUGGCUC 22

Intron2-3109 18209

CFTR-

- AAAAGGAACGAAUUUAUUGGCUC 23

Intron2-3110 18210

CFTR-

- UAAAAGGAACGAAUUUAUUGGCUC 24

lntron2-3111 18211

CFTR-

- CUGUAUUGCCUUGCUCUC 18

lntron2-3112 18212

CFTR-

- UCUGUAUUGCCUUGCUCUC 19

lntron2-3113 18213

CFTR-

- GUCUGUAUUGCCUUGCUCUC 20

lntron2-3114 18214

CFTR-

- GGUCUGUAUUGCCUUGCUCUC 21

lntron2-3115 18215

CFTR-

- AGGUCUGUAUUGCCUUGCUCUC 22

lntron2-3116 18216

CFTR-

- GAGGUCUGUAUUGCCUUGCUCUC 23

lntron2-3117 18217

CFTR-

- UGAGGUCUGUAUUGCCUUGCUCUC 24

lntron2-3118 18218

CFTR-

- AUGCUGGCCAGGCUGGUC 18

lntron2-3119 18219

574

5535.1 CFTR-

- UAUGCUGGCCAGGCUGGUC 19

Intron2-3120 18220

CFTR-

- CUAUGCUGGCCAGGCUGGUC 20

lntron2-3121 18221

CFTR-

- GCUAUGCUGGCCAGGCUGGUC 21

lntron2-3122 18222

CFTR-

- UGCUAUGCUGGCCAGGCUGGUC 22

lntron2-3123 18223

CFTR-

- UUGCUAUGCUGGCCAGGCUGGUC 23

lntron2-3124 18224

CFTR-

- UUUGCUAUGCUGGCCAGGCUGGUC 24

lntron2-3125 18225

CFTR-

- AUGUUGGCCAGGCUGGUC 18

lntron2-3126 18226

CFTR-

- CAUGUUGGCCAGGCUGGUC 19

lntron2-3127 18227

CFTR-

- CCAUGUUGGCCAGGCUGGUC 20

lntron2-3128 18228

CFTR-

- GCCAUGUUGGCCAGGCUGGUC 21

lntron2-3129 18229

CFTR-

- CGCCAUGUUGGCCAGGCUGGUC 22

Intron2-3130 18230

CFTR-

- UCGCCAUGUUGGCCAGGCUGGUC 23

lntron2-3131 18231

CFTR-

- UUCGCCAUGUUGGCCAGGCUGGUC 24

lntron2-3132 18232

CFTR-

- CUCUCAUUAGCAAGCUUC 18

lntron2-3133 18233

CFTR-

- GCUCUCAUUAGCAAGCUUC 19

lntron2-3134 18234

CFTR-

- GGCUCUCAUUAGCAAGCUUC 20

lntron2-3135 18235

CFTR-

- GGGCUCUCAUUAGCAAGCUUC 21

lntron2-3136 18236

CFTR-

- AGGGCUCUCAUUAGCAAGCUUC 22

lntron2-3137 18237

CFTR-

- AAGGGCUCUCAUUAGCAAGCUUC 23

lntron2-3138 18238

CFTR-

- GAAGGGCUCUCAUUAGCAAGCUUC 24

lntron2-3139 18239

CFTR-

- AGUUCUUCCUUGUGGUUC 18

Intron2-3140 18240

575

5535.1 CFTR-

- UAGUUCUUCCUUGUGGUUC 19

lntron2-3141 18241

CFTR-

- CUAGUUCUUCCUUGUGGUUC 20

lntron2-3142 18242

CFTR-

- CCUAGUUCUUCCUUGUGGUUC 21

lntron2-3143 18243

CFTR-

- ACCUAGUUCUUCCUUGUGGUUC 22

lntron2-3144 18244

CFTR-

- UACCUAGUUCUUCCUUGUGGUUC 23

lntron2-3145 18245

CFTR-

- UUACCUAGUUCUUCCUUGUGGUUC 24

lntron2-3146 18246

CFTR-

- UCUGUGUGUGAGAGAAAG 18

lntron2-3147 18247

CFTR-

- CUCUGUGUGUGAGAGAAAG 19

lntron2-3148 18248

CFTR-

- GCUCUGUGUGUGAGAGAAAG 20

lntron2-3149 18249

CFTR-

- AGCUCUGUGUGUGAGAGAAAG 21

Intron2-3150 18250

CFTR-

- UAGCUCUGUGUGUGAGAGAAAG 22

lntron2-3151 18251

CFTR-

- UUAGCUCUGUGUGUGAGAGAAAG 23

lntron2-3152 18252

CFTR-

- GUUAGCUCUGUGUGUGAGAGAAAG 24

lntron2-3153 18253

CFTR-

- CUUUAAGGACCACGAAAG 18

lntron2-3154 18254

CFTR-

- UCUUUAAGGACCACGAAAG 19

lntron2-3155 18255

CFTR-

- AU CU U U AAGG ACCACG AAAG 20

lntron2-3156 18256

CFTR-

- U AU CU U U AAGG ACCACG AAAG 21

lntron2-3157 18257

CFTR-

- CUAUCUUUAAGGACCACGAAAG 22

lntron2-3158 18258

CFTR-

- CCUAUCUU U AAGG ACCACG AAAG 23

lntron2-3159 18259

CFTR-

- UCCUAUCUUUAAGGACCACGAAAG 24

Intron2-3160 18260

CFTR-

- AUGGAGCCAUGAUUCCAG 18

lntron2-3161 18261

576

5535.1 CFTR-

- GAUGGAGCCAUGAUUCCAG 19

lntron2-3162 18262

CFTR-

- UGAUGGAGCCAUGAUUCCAG 20

lntron2-3163 18263

CFTR-

- AUGAUGGAGCCAUGAUUCCAG 21

lntron2-3164 18264

CFTR-

- AAUGAUGGAGCCAUGAUUCCAG 22

lntron2-3165 18265

CFTR-

- GAAUGAUGGAGCCAUGAUUCCAG 23

lntron2-3166 18266

CFTR-

- UGAAUGAUGGAGCCAUGAUUCCAG 24

lntron2-3167 18267

CFTR-

- GGGAAUGAUUAAUCAGAG 18

lntron2-3168 18268

CFTR-

- AGGGAAUGAUUAAUCAGAG 19

lntron2-3169 18269

CFTR-

- GAGGGAAUGAUUAAUCAGAG 20

Intron2-3170 18270

CFTR-

- UGAGGGAAUGAUUAAUCAGAG 21

lntron2-3171 18271

CFTR-

- CUGAGGGAAUGAUUAAUCAGAG 22

lntron2-3172 18272

CFTR-

- GCUGAGGGAAUGAUUAAUCAGAG 23

lntron2-3173 18273

CFTR-

- UGCUGAGGGAAUGAUUAAUCAGAG 24

lntron2-3174 18274

CFTR-

- UGGCUAAUUUUUGUAGAG 18

lntron2-3175 18275

CFTR-

- CUGGCUAAUUUUUGUAGAG 19

lntron2-3176 18276

CFTR-

- CCUGGCUAAUUUUUGUAGAG 20

lntron2-3177 18277

CFTR-

- GCCUGGCUAAUUUUUGUAGAG 21

lntron2-3178 18278

CFTR-

- GGCCUGGCUAAUUUUUGUAGAG 22

lntron2-3179 18279

CFTR-

- AGGCCUGGCUAAUUUUUGUAGAG 23

Intron2-3180 18280

CFTR-

- CAGGCCUGGCUAAUUUUUGUAGAG 24

lntron2-3181 18281

CFTR-

- CCUCUCAGCCACUCUGAG 18

lntron2-3182 18282

577

5535.1 CFTR-

- UCCUCUCAGCCACUCUGAG 19

lntron2-3183 18283

CFTR-

- CUCCUCUCAGCCACUCUGAG 20

lntron2-344 15444

CFTR-

- UCUCCUCUCAGCCACUCUGAG 21

lntron2-3184 18284

CFTR-

- AUCUCCUCUCAGCCACUCUGAG 22

lntron2-3185 18285

CFTR-

- UAUCUCCUCUCAGCCACUCUGAG 23

lntron2-3186 18286

CFTR-

- AUAUCUCCUCUCAGCCACUCUGAG 24

lntron2-3187 18287

CFTR-

- AUGUGGGGAGGGAAAUAG 18

lntron2-3188 18288

CFTR-

- CAUGUGGGGAGGGAAAUAG 19

lntron2-3189 18289

CFTR-

- GCAUGUGGGGAGGGAAAUAG 20

Intron2-3190 18290

CFTR-

- AGCAUGUGGGGAGGGAAAUAG 21

lntron2-3191 18291

CFTR-

- AAGCAUGUGGGGAGGGAAAUAG 22

lntron2-3192 18292

CFTR-

- GAAGCAUGUGGGGAGGGAAAUAG 23

lntron2-3193 18293

CFTR-

- AGAAGCAUGUGGGGAGGGAAAUAG 24

lntron2-3194 18294

CFTR-

- GGUAAUUAGGCUUUAUAG 18

lntron2-3195 18295

CFTR-

- AGGUAAUUAGGCUUUAUAG 19

lntron2-3196 18296

CFTR-

- AAGGUAAUUAGGCUUUAUAG 20

lntron2-3197 18297

CFTR-

- AAAGGUAAUUAGGCUUUAUAG 21

lntron2-3198 18298

CFTR-

- AAAAGGUAAUUAGGCUUUAUAG 22

lntron2-3199 18299

CFTR-

- GAAAAGGUAAUUAGGCUUUAUAG 23

Intron2-3200 18300

CFTR-

- GGAAAAGGUAAUUAGGCUUUAUAG 24

Intron2-3201 18301

CFTR-

- AACUAUGUGAAGACCUAG 18

Intron2-3202 18302

578

5535.1 CFTR-

- GAACUAUGUGAAGACCUAG 19

Intron2-3203 18303

CFTR-

- UGAACUAUGUGAAGACCUAG 20

Intron2-3204 18304

CFTR-

- CUGAACUAUGUGAAGACCUAG 21

Intron2-3205 18305

CFTR-

- CCUGAACUAUGUGAAGACCUAG 22

Intron2-3206 18306

CFTR-

- GCCUGAACUAUGUGAAGACCUAG 23

Intron2-3207 18307

CFTR-

- AGCCUGAACUAUGUGAAGACCUAG 24

Intron2-3208 18308

CFTR-

- U U CAAAG AAU UAAGCU AG 18

Intron2-3209 18309

CFTR-

- A U U CAAAG A A UUAAGCUAG 19

Intron2-3210 18310

CFTR-

- U A U U CAAAG A A UUAAGCUAG 20

lntron2-345 15445

CFTR-

- UUAUUCAAAGAAUUAAGCUAG 21

lntron2-3211 18311

CFTR-

- UUUAUUCAAAGAAUUAAGCUAG 22

lntron2-3212 18312

CFTR-

- UUUUAUUCAAAGAAUUAAGCUAG 23

lntron2-3213 18313

CFTR-

- AUUUUAUU CAAAG AAU U AAG CU AG 24

lntron2-3214 18314

CFTR-

- UCUCAGUCUCCUGAGUAG 18

lntron2-3215 18315

CFTR-

- AUCUCAGUCUCCUGAGUAG 19

lntron2-3216 18316

CFTR-

- AAUCUCAGUCUCCUGAGUAG 20

lntron2-3217 18317

CFTR-

- GAAUCUCAGUCUCCUGAGUAG 21

lntron2-3218 18318

CFTR-

- CGAAUCUCAGUCUCCUGAGUAG 22

lntron2-3219 18319

CFTR-

- GCGAAUCUCAGUCUCCUGAGUAG 23

Intron2-3220 18320

CFTR-

- AGCGAAUCUCAGUCUCCUGAGUAG 24

lntron2-3221 18321

CFTR-

- AAUACAUGAUUUUAGUAG 18

lntron2-3222 18322

579

5535.1 CFTR-

- UAAUACAUGAUUUUAGUAG 19

lntron2-3223 18323

CFTR-

- UUAAUACAUGAUUUUAGUAG 20

lntron2-3224 18324

CFTR-

- UUUAAUACAUGAUUUUAGUAG 21

lntron2-3225 18325

CFTR-

- CUUUAAUACAUGAUUUUAGUAG 22

lntron2-3226 18326

CFTR-

- CCUUUAAUACAUGAUUUUAGUAG 23

lntron2-3227 18327

CFTR-

- ACCUUUAAUACAUGAUUUUAGUAG 24

lntron2-3228 18328

CFTR-

- CUGUGUGUGAGAGAAAGG 18

lntron2-3229 18329

CFTR-

- UCUGUGUGUGAGAGAAAGG 19

Intron2-3230 18330

CFTR-

- CUCUGUGUGUGAGAGAAAGG 20

lntron2-678 15778

CFTR-

- GCUCUGUGUGUGAGAGAAAGG 21

lntron2-3231 18331

CFTR-

- AGCUCUGUGUGUGAGAGAAAGG 22

lntron2-3232 18332

CFTR-

- UAGCUCUGUGUGUGAGAGAAAGG 23

lntron2-3233 18333

CFTR-

- UUAGCUCUGUGUGUGAGAGAAAGG 24

lntron2-3234 18334

CFTR-

- CUCGCUGUGUCACCCAGG 18

lntron2-3235 18335

CFTR-

- UCUCGCUGUGUCACCCAGG 19

lntron2-3236 18336

CFTR-

- GUCUCGCUGUGUCACCCAGG 20

lntron2-3237 18337

CFTR-

- AGUCUCGCUGUGUCACCCAGG 21

lntron2-3238 18338

CFTR-

- GAGUCUCGCUGUGUCACCCAGG 22

lntron2-3239 18339

CFTR-

- AGAGUCUCGCUGUGUCACCCAGG 23

Intron2-3240 18340

CFTR-

- CAGAGUCUCGCUGUGUCACCCAGG 24

lntron2-3241 18341

CFTR-

- CUUGCUCUGUUGCCCAGG 18

lntron2-3242 18342

580

5535.1 CFTR-

- UCUUGCUCUGUUGCCCAGG 19

lntron2-3243 18343

CFTR-

- GUCUUGCUCUGUUGCCCAGG 20

lntron2-3244 18344

CFTR-

- AGUCUUGCUCUGUUGCCCAGG 21

lntron2-3245 18345

CFTR-

- GAGUCUUGCUCUGUUGCCCAGG 22

lntron2-3246 18346

CFTR-

- AGAGUCUUGCUCUGUUGCCCAGG 23

lntron2-3247 18347

CFTR-

- CAGAGUCUUGCUCUGUUGCCCAGG 24

lntron2-3248 18348

CFTR-

- UGUGCAAAUGCCAUGAGG 18

lntron2-3249 18349

CFTR-

- GUGUGCAAAUGCCAUGAGG 19

Intron2-3250 18350

CFTR-

- UGUGUGCAAAUGCCAUGAGG 20

lntron2-3251 18351

CFTR-

- GUGUGUGCAAAUGCCAUGAGG 21

lntron2-3252 18352

CFTR-

- GGUGUGUGCAAAUGCCAUGAGG 22

lntron2-3253 18353

CFTR-

- UGGUGUGUGCAAAUGCCAUGAGG 23

lntron2-3254 18354

CFTR-

- UUGGUGUGUGCAAAUGCCAUGAGG 24

lntron2-3255 18355

CFTR-

- ACUAUGUGAAGACCUAGG 18

lntron2-3256 18356

CFTR-

- AACUAUGUGAAGACCUAGG 19

lntron2-3257 18357

CFTR-

- GAACUAUGUGAAGACCUAGG 20

lntron2-69 15169

CFTR-

- UGAACUAUGUGAAGACCUAGG 21

lntron2-3258 18358

CFTR-

- CUGAACUAUGUGAAGACCUAGG 22

lntron2-3259 18359

CFTR-

- CCUGAACUAUGUGAAGACCUAGG 23

Intron2-3260 18360

CFTR-

- GCCUGAACUAUGUGAAGACCUAGG 24

lntron2-3261 18361

CFTR-

- GUGGAGAAGCAUGUGGGG 18

lntron2-3262 18362

581

5535.1 CFTR-

- GGUGGAGAAGCAUGUGGGG 19

lntron2-3263 18363

CFTR-

- AGGUGGAGAAGCAUGUGGGG 20

lntron2-682 15782

CFTR-

- AAGGUGGAGAAGCAUGUGGGG 21

lntron2-3264 18364

CFTR-

- AAAGGUGGAGAAGCAUGUGGGG 22

lntron2-3265 18365

CFTR-

- GAAAGGUGGAGAAGCAUGUGGGG 23

lntron2-3266 18366

CFTR-

- AGAAAGGUGGAGAAGCAUGUGGGG 24

lntron2-3267 18367

CFTR-

- GGUGGAGAAGCAUGUGGG 18

lntron2-3268 18368

CFTR-

- AGGUGGAGAAGCAUGUGGG 19

lntron2-3269 18369

CFTR-

- AAGGUGGAGAAGCAUGUGGG 20

Intron2-3270 18370

CFTR-

- AAAGGUGGAGAAGCAUGUGGG 21

lntron2-3271 18371

CFTR-

- GAAAGGUGGAGAAGCAUGUGGG 22

lntron2-3272 18372

CFTR-

- AGAAAGGUGGAGAAGCAUGUGGG 23

lntron2-3273 18373

CFTR-

- GAGAAAGGUGGAGAAGCAUGUGGG 24

lntron2-3274 18374

CFTR-

- CAAGUGGUUGCCAGAUGG 18

lntron2-3275 18375

CFTR-

- UCAAGUGGUUGCCAGAUGG 19

lntron2-3276 18376

CFTR-

- CUCAAGUGGUUGCCAGAUGG 20

lntron2-3277 18377

CFTR-

- CCUCAAGUGGUUGCCAGAUGG 21

lntron2-3278 18378

CFTR-

- CCCUCAAGUGGUUGCCAGAUGG 22

lntron2-3279 18379

CFTR-

- GCCCUCAAGUGGUUGCCAGAUGG 23

Intron2-3280 18380

CFTR-

- GGCCCUCAAGUGGUUGCCAGAUGG 24

lntron2-3281 18381

CFTR-

- AGUAACCAAAUGUUAUGG 18

lntron2-3282 18382

582

5535.1 CFTR-

- GAGUAACCAAAUGUUAUGG 19

lntron2-3283 18383

CFTR-

- UGAGUAACCAAAUGUUAUGG 20

lntron2-3284 18384

CFTR-

- CUGAGUAACCAAAUGUUAUGG 21

lntron2-3285 18385

CFTR-

- UCUGAGUAACCAAAUGUUAUGG 22

lntron2-3286 18386

CFTR-

- CUCUGAGUAACCAAAUGUUAUGG 23

lntron2-3287 18387

CFTR-

- ACUCUGAGUAACCAAAUGUUAUGG 24

lntron2-3288 18388

CFTR-

- CCUUGGCCUCCCAAAAUG 18

lntron2-3289 18389

CFTR-

- ACCUUGGCCUCCCAAAAUG 19

Intron2-3290 18390

CFTR-

- CACCUUGGCCUCCCAAAAUG 20

lntron2-3291 18391

CFTR-

- CCACCUUGGCCUCCCAAAAUG 21

lntron2-3292 18392

CFTR-

- CCCACCUUGGCCUCCCAAAAUG 22

lntron2-3293 18393

CFTR-

- GCCCACCUUGGCCUCCCAAAAUG 23

lntron2-3294 18394

CFTR-

- UGCCCACCUUGGCCUCCCAAAAUG 24

lntron2-3295 18395

CFTR-

- UUUGCCAGUUAAUGAAUG 18

lntron2-3296 18396

CFTR-

- CUUUGCCAGUUAAUGAAUG 19

lntron2-3297 18397

CFTR-

- ACUUUGCCAGUUAAUGAAUG 20

lntron2-3298 18398

CFTR-

- UACUUUGCCAGUUAAUGAAUG 21

lntron2-3299 18399

CFTR-

- AUACUUUGCCAGUUAAUGAAUG 22

Intron2-3300 18400

CFTR-

- UAUACUUUGCCAGUUAAUGAAUG 23

Intron2-3301 18401

CFTR-

- AUAUACUUUGCCAGUUAAUGAAUG 24

Intron2-3302 18402

CFTR-

- UUGUUGAAUGAAUCCAUG 18

Intron2-3303 18403

583

5535.1 CFTR-

- UUUGUUGAAUGAAUCCAUG 19

Intron2-3304 18404

CFTR-

- AUUUGUUGAAUGAAUCCAUG 20

Intron2-3305 18405

CFTR-

- UAUUUGUUGAAUGAAUCCAUG 21

Intron2-3306 18406

CFTR-

- AUAUUUGUUGAAUGAAUCCAUG 22

Intron2-3307 18407

CFTR-

- AAUAUUUGUUGAAUGAAUCCAUG 23

Intron2-3308 18408

CFTR-

- AAAUAUUUGUUGAAUGAAUCCAUG 24

Intron2-3309 18409

CFTR-

- GAAAGGUGGAGAAGCAUG 18

Intron2-3310 18410

CFTR-

- AGAAAGGUGGAGAAGCAUG 19

lntron2-3311 18411

CFTR-

- GAGAAAGGUGGAGAAGCAUG 20

lntron2-467 15567

CFTR-

- AGAGAAAGGUGGAGAAGCAUG 21

lntron2-3312 18412

CFTR-

- GAGAGAAAGGUGGAGAAGCAUG 22

lntron2-3313 18413

CFTR-

- UGAGAGAAAGGUGGAGAAGCAUG 23

lntron2-3314 18414

CFTR-

- GUGAGAGAAAGGUGGAGAAGCAUG 24

lntron2-3315 18415

CFTR-

- CUAAGUUUUAAUUGGAUG 18

lntron2-3316 18416

CFTR-

- UCUAAGUUUUAAUUGGAUG 19

lntron2-3317 18417

CFTR-

- AUCUAAGUUUUAAUUGGAUG 20

lntron2-3318 18418

CFTR-

- UAUCUAAGUUUUAAUUGGAUG 21

lntron2-3319 18419

CFTR-

- AUAUCUAAGUUUUAAUUGGAUG 22

Intron2-3320 18420

CFTR-

- AAUAUCUAAGUUUUAAUUGGAUG 23

lntron2-3321 18421

CFTR-

- GAAUAUCUAAGUUUUAAUUGGAUG 24

lntron2-3322 18422

CFTR-

- UCCAUUUCUCCUUUGAUG 18

lntron2-3323 18423

584

5535.1 CFTR-

- AUCCAUUUCUCCUUUGAUG 19

lntron2-3324 18424

CFTR-

- GAUCCAUUUCUCCUUUGAUG 20

lntron2-3325 18425

CFTR-

- UGAUCCAUUUCUCCUUUGAUG 21

lntron2-3326 18426

CFTR-

- CUGAUCCAUUUCUCCUUUGAUG 22

lntron2-3327 18427

CFTR-

- UCUGAUCCAUUUCUCCUUUGAUG 23

lntron2-3328 18428

CFTR-

- AUCUGAUCCAUUUCUCCUUUGAUG 24

lntron2-3329 18429

CFTR-

- UAAUGGGAAUAACCACUG 18

Intron2-3330 18430

CFTR-

- GUAAUGGGAAUAACCACUG 19

lntron2-3331 18431

CFTR-

- AGUAAUGGGAAUAACCACUG 20

lntron2-3332 18432

CFTR-

- CAGUAAUGGGAAUAACCACUG 21

lntron2-3333 18433

CFTR-

- ACAGUAAUGGGAAUAACCACUG 22

lntron2-3334 18434

CFTR-

- GACAGUAAUGGGAAUAACCACUG 23

lntron2-3335 18435

CFTR-

- UGACAGUAAUGGGAAUAACCACUG 24

lntron2-3336 18436

CFTR-

- AGUUUUAAUUGGAUGCUG 18

lntron2-3337 18437

CFTR-

- AAGUUUUAAUUGGAUGCUG 19

lntron2-3338 18438

CFTR-

- UAAGUUUUAAUUGGAUGCUG 20

lntron2-364 15464

CFTR-

- CUAAGUUUUAAUUGGAUGCUG 21

lntron2-3339 18439

CFTR-

- UCUAAGUUUUAAUUGGAUGCUG 22

Intron2-3340 18440

CFTR-

- AUCUAAGUUUUAAUUGGAUGCUG 23

lntron2-3341 18441

CFTR-

- UAUCUAAGUUUUAAUUGGAUGCUG 24

lntron2-3342 18442

CFTR-

- AAACCUGUAGCAUUGCUG 18

lntron2-3343 18443

585

5535.1 CFTR-

- GAAACCUGUAGCAUUGCUG 19

lntron2-3344 18444

CFTR-

- AGAAACCUGUAGCAUUGCUG 20

lntron2-3345 18445

CFTR-

- UAGAAACCUGUAGCAUUGCUG 21

lntron2-3346 18446

CFTR-

- AUAGAAACCUGUAGCAUUGCUG 22

lntron2-3347 18447

CFTR-

- CAUAGAAACCUGUAGCAUUGCUG 23

lntron2-3348 18448

CFTR-

- ACAUAGAAACCUGUAGCAUUGCUG 24

lntron2-3349 18449

CFTR-

- CCUUGGCCUCCCAAAGUG 18

Intron2-3350 18450

CFTR-

- GCCUUGGCCUCCCAAAGUG 19

lntron2-3351 18451

CFTR-

- CGCCUUGGCCUCCCAAAGUG 20

lntron2-3352 18452

CFTR-

- CCGCCUUGGCCUCCCAAAGUG 21

lntron2-3353 18453

CFTR-

- CCCGCCUUGGCCUCCCAAAGUG 22

lntron2-3354 18454

CFTR-

- GCCCGCCUUGGCCUCCCAAAGUG 23

lntron2-3355 18455

CFTR-

- UGCCCGCCUUGGCCUCCCAAAGUG 24

lntron2-3356 18456

CFTR-

- CAGAUAAAAGGGUGAGUG 18

lntron2-3357 18457

CFTR-

- CCAGAUAAAAGGGUGAGUG 19

lntron2-3358 18458

CFTR-

- GCCAGAUAAAAGGGUGAGUG 20

lntron2-3359 18459

CFTR-

- UGCCAGAUAAAAGGGUGAGUG 21

Intron2-3360 18460

CFTR-

- AUGCCAGAUAAAAGGGUGAGUG 22

lntron2-3361 18461

CFTR-

- GAUGCCAGAUAAAAGGGUGAGUG 23

lntron2-3362 18462

CFTR-

- UGAUGCCAGAUAAAAGGGUGAGUG 24

lntron2-3363 18463

CFTR-

- GUGUGUGAGAGAAAGGUG 18

lntron2-3364 18464

586

5535.1 CFTR-

- UGUGUGUGAGAGAAAGGUG 19

lntron2-3365 18465

CFTR-

- CUGUGUGUGAGAGAAAGGUG 20

lntron2-3366 18466

CFTR-

- UCUGUGUGUGAGAGAAAGGUG 21

lntron2-3367 18467

CFTR-

- CUCUGUGUGUGAGAGAAAGGUG 22

lntron2-3368 18468

CFTR-

- GCUCUGUGUGUGAGAGAAAGGUG 23

lntron2-3369 18469

CFTR-

- AGCUCUGUGUGUGAGAGAAAGGUG 24

Intron2-3370 18470

CFTR-

- UAUGUGAAGACCUAGGUG 18

lntron2-3371 18471

CFTR-

- CUAUGUGAAGACCUAGGUG 19

lntron2-3372 18472

CFTR-

- ACUAUGUGAAGACCUAGGUG 20

lntron2-3373 18473

CFTR-

- AACUAUGUGAAGACCUAGGUG 21

lntron2-3374 18474

CFTR-

- GAACUAUGUGAAGACCUAGGUG 22

lntron2-3375 18475

CFTR-

- UGAACUAUGUGAAGACCUAGGUG 23

lntron2-3376 18476

CFTR-

- CUGAACUAUGUGAAGACCUAGGUG 24

lntron2-3377 18477

CFTR-

- AAGGUGGAGAAGCAUGUG 18

lntron2-3378 18478

CFTR-

- AAAGGUGGAGAAGCAUGUG 19

lntron2-3379 18479

CFTR-

- GAAAGGUGGAGAAGCAUGUG 20

lntron2-468 15568

CFTR-

- AGAAAGGUGGAGAAGCAUGUG 21

Intron2-3380 18480

CFTR-

- GAGAAAGGUGGAGAAGCAUGUG 22

lntron2-3381 18481

CFTR-

- AGAGAAAGGUGGAGAAGCAUGUG 23

lntron2-3382 18482

CFTR-

- GAGAGAAAGGUGGAGAAGCAUGUG 24

lntron2-3383 18483

CFTR-

- AUAUUUUAUUCCUUUGUG 18

lntron2-3384 18484

587

5535.1 CFTR-

- GAUAUUUUAUUCCUUUGUG 19

lntron2-3385 18485

CFTR-

- AGAUAUUUUAUUCCUUUGUG 20

lntron2-3386 18486

CFTR-

- GAGAUAUUUUAUUCCUUUGUG 21

lntron2-3387 18487

CFTR-

- AGAGAUAUUUUAUUCCUUUGUG 22

lntron2-3388 18488

CFTR-

- UAGAGAUAUUUUAUUCCUUUGUG 23

lntron2-3389 18489

CFTR-

- UUAGAGAUAUUUUAUUCCUUUGUG 24

Intron2-3390 18490

CFTR-

- UAGAAACCUGUAGCAUUG 18

lntron2-3391 18491

CFTR-

- AUAGAAACCUGUAGCAUUG 19

lntron2-3392 18492

CFTR-

- CAUAGAAACCUGUAGCAUUG 20

lntron2-3393 18493

CFTR-

- ACAUAGAAACCUGUAGCAUUG 21

lntron2-3394 18494

CFTR-

- UACAUAGAAACCUGUAGCAUUG 22

lntron2-3395 18495

CFTR-

- UUACAUAGAAACCUGUAGCAUUG 23

lntron2-3396 18496

CFTR-

- AUUACAUAGAAACCUGUAGCAUUG 24

lntron2-3397 18497

CFTR-

- GUGGUUGCCAGAUGGUUG 18

lntron2-3398 18498

CFTR-

- AGUGGUUGCCAGAUGGUUG 19

lntron2-3399 18499

CFTR-

- AAGUGGUUGCCAGAUGGUUG 20

Intron2-3400 18500

CFTR-

- CAAGUGGUUGCCAGAUGGUUG 21

Intron2-3401 18501

CFTR-

- UCAAGUGGUUGCCAGAUGGUUG 22

Intron2-3402 18502

CFTR-

- CUCAAGUGGUUGCCAGAUGGUUG 23

Intron2-3403 18503

CFTR-

- CCUCAAGUGGUUGCCAGAUGGUUG 24

Intron2-3404 18504

CFTR-

- UGAUCCAUUUCUCCUUUG 18

Intron2-3405 18505

588

5535.1 CFTR-

- CUGAUCCAUUUCUCCUUUG 19

Intron2-3406 18506

CFTR-

- UCUGAUCCAUUUCUCCUUUG 20

Intron2-3407 18507

CFTR-

- AUCUGAUCCAUUUCUCCUUUG 21

Intron2-3408 18508

CFTR-

- CAUCUGAUCCAUUUCUCCUUUG 22

Intron2-3409 18509

CFTR-

- CCAUCUGAUCCAUUUCUCCUUUG 23

Intron2-3410 18510

CFTR-

- CCCAUCUGAUCCAUUUCUCCUUUG 24

lntron2-3411 18511

CFTR-

- AGGCCUGGCUAAUUUUUG 18

lntron2-3412 18512

CFTR-

- CAGGCCUGGCUAAUUUUUG 19

lntron2-3413 18513

CFTR-

- CCAGGCCUGGCUAAUUUUUG 20

lntron2-3414 18514

CFTR-

- ACCAGGCCUGGCUAAUUUUUG 21

lntron2-3415 18515

CFTR-

- CACCAGGCCUGGCUAAUUUUUG 22

lntron2-3416 18516

CFTR-

- CCACCAGGCCUGGCUAAUUUUUG 23

lntron2-3417 18517

CFTR-

- ACCACCAGGCCUGGCUAAUUUUUG 24

lntron2-3418 18518

CFTR-

- CUUUGUCCUUGGCUAAAU 18

lntron2-3419 18519

CFTR-

- CCUUUGUCCUUGGCUAAAU 19

Intron2-3420 18520

CFTR-

- CCCUUUGUCCUUGGCUAAAU 20

lntron2-3421 18521

CFTR-

- GCCCUUUGUCCUUGGCUAAAU 21

lntron2-3422 18522

CFTR-

- AGCCCUUUGUCCUUGGCUAAAU 22

lntron2-3423 18523

CFTR-

- GAGCCCUUUGUCCUUGGCUAAAU 23

lntron2-3424 18524

CFTR-

- GGAGCCCUUUGUCCUUGGCUAAAU 24

lntron2-3425 18525

CFTR-

- AUGAAUCCAUGAUGGAAU 18

lntron2-3426 18526

589

5535.1 CFTR-

- AAUGAAUCCAUGAUGGAAU 19

lntron2-3427 18527

CFTR-

- GAAUGAAUCCAUGAUGGAAU 20

lntron2-3428 18528

CFTR-

- UGAAUGAAUCCAUGAUGGAAU 21

lntron2-3429 18529

CFTR-

- UUGAAUGAAUCCAUGAUGGAAU 22

Intron2-3430 18530

CFTR-

- GU UGAAUGAAUCCAUGAUGGAAU 23

lntron2-3431 18531

CFTR-

- UGUUGAAUGAAUCCAUGAUGGAAU 24

lntron2-3432 18532

CFTR-

- AGAAAGGUGGAGAAGCAU 18

lntron2-3433 18533

CFTR-

- GAGAAAGGUGGAGAAGCAU 19

lntron2-3434 18534

CFTR-

- AGAGAAAGGUGGAGAAGCAU 20

lntron2-3435 18535

CFTR-

- GAGAGAAAGGUGGAGAAGCAU 21

lntron2-3436 18536

CFTR-

- UGAGAGAAAGGUGGAGAAGCAU 22

lntron2-3437 18537

CFTR-

- GUGAGAGAAAGGUGGAGAAGCAU 23

lntron2-3438 18538

CFTR-

- UGUGAGAGAAAGGUGGAGAAGCAU 24

lntron2-3439 18539

CFTR-

- GUGGGGAGGGAAAUAGAU 18

Intron2-3440 18540

CFTR-

- UGUGGGGAGGGAAAUAGAU 19

lntron2-3441 18541

CFTR-

- AUGUGGGGAGGGAAAUAGAU 20

lntron2-377 15477

CFTR-

- CAUGUGGGGAGGGAAAUAGAU 21

lntron2-3442 18542

CFTR-

- GCAUGUGGGGAGGGAAAUAGAU 22

lntron2-3443 18543

CFTR-

- AGCAUGUGGGGAGGGAAAUAGAU 23

lntron2-3444 18544

CFTR-

- AAGCAUGUGGGGAGGGAAAUAGAU 24

lntron2-3445 18545

CFTR-

- UUUUGUAUUUUAGUAGAU 18

lntron2-3446 18546

590

5535.1 CFTR-

- UUUUUGUAUUUUAGUAGAU 19

lntron2-3447 18547

CFTR-

- AUUUUUGUAUUUUAGUAGAU 20

lntron2-3448 18548

CFTR-

- AAUUUUUGUAUUUUAGUAGAU 21

lntron2-3449 18549

CFTR-

- UAAUUUUUGUAUUUUAGUAGAU 22

Intron2-3450 18550

CFTR-

- CUAAUUUUUGUAUUUUAGUAGAU 23

lntron2-3451 18551

CFTR-

- GCUAAUUUUUGUAUUUUAGUAGAU 24

lntron2-3452 18552

CFTR-

- CAAGAUUGUAGUCAGGAU 18

lntron2-3453 18553

CFTR-

- CCAAGAUUGUAGUCAGGAU 19

lntron2-3454 18554

CFTR-

- UCCAAGAUUGUAGUCAGGAU 20

lntron2-3455 18555

CFTR-

- U U CCAAG AU UG U AG U CAGG AU 21

lntron2-3456 18556

CFTR-

- GU UCCAAGAUUGUAGUCAGGAU 22

lntron2-3457 18557

CFTR-

- CG U U CCAAG AU UG U AG U CAGG AU 23

lntron2-3458 18558

CFTR-

- CCGUUCCAAGAUUGUAGUCAGGAU 24

lntron2-3459 18559

CFTR-

- UAACCAAAUGUUAUGGAU 18

Intron2-3460 18560

CFTR-

- GUAACCAAAUGUUAUGGAU 19

lntron2-3461 18561

CFTR-

- AGUAACCAAAUGUUAUGGAU 20

lntron2-378 15478

CFTR-

- GAGUAACCAAAUGUUAUGGAU 21

lntron2-3462 18562

CFTR-

- UGAGUAACCAAAUGUUAUGGAU 22

lntron2-3463 18563

CFTR-

- CUGAGUAACCAAAUGUUAUGGAU 23

lntron2-3464 18564

CFTR-

- UCUGAGUAACCAAAUGUUAUGGAU 24

lntron2-3465 18565

CFTR-

- AACUUCUUCCCUUCUGAU 18

lntron2-3466 18566

591

5535.1 CFTR-

- AAACUUCUUCCCUUCUGAU 19

lntron2-3467 18567

CFTR-

- AAAACUUCUUCCCUUCUGAU 20

lntron2-3468 18568

CFTR-

- UAAAACUUCUUCCCUUCUGAU 21

lntron2-3469 18569

CFTR-

- AUAAAACUUCUUCCCUUCUGAU 22

Intron2-3470 18570

CFTR-

- AAUAAAACUUCUUCCCUUCUGAU 23

lntron2-3471 18571

CFTR-

- GAAUAAAACUUCUUCCCUUCUGAU 24

lntron2-3472 18572

CFTR-

- UCAUGAAGCCUGAACUAU 18

lntron2-3473 18573

CFTR-

- CUCAUGAAGCCUGAACUAU 19

lntron2-3474 18574

CFTR-

- GCUCAUGAAGCCUGAACUAU 20

lntron2-3475 18575

CFTR-

- GGCUCAUGAAGCCUGAACUAU 21

lntron2-3476 18576

CFTR-

- UGGCUCAUGAAGCCUGAACUAU 22

lntron2-3477 18577

CFTR-

- UUGGCUCAUGAAGCCUGAACUAU 23

lntron2-3478 18578

CFTR-

- AUUGGCUCAUGAAGCCUGAACUAU 24

lntron2-3479 18579

CFTR-

- UUCUUAUAAAAUUGGUAU 18

Intron2-3480 18580

CFTR-

- UUUCUUAUAAAAUUGGUAU 19

lntron2-3481 18581

CFTR-

- UUUUCUUAUAAAAUUGGUAU 20

lntron2-3482 18582

CFTR-

- CUUUUCUUAUAAAAUUGGUAU 21

lntron2-3483 18583

CFTR-

- UCUUUUCUUAUAAAAUUGGUAU 22

lntron2-3484 18584

CFTR-

- UUCUUUUCUUAUAAAAUUGGUAU 23

lntron2-3485 18585

CFTR-

- CUUCUUUUCUUAUAAAAUUGGUAU 24

lntron2-3486 18586

CFTR-

- UCAGAGAAUUUGUCUUAU 18

lntron2-3487 18587

592

5535.1 CFTR-

- UUCAGAGAAUUUGUCUUAU 19

lntron2-3488 18588

CFTR-

- UUUCAGAGAAUUUGUCUUAU 20

lntron2-3489 18589

CFTR-

- GUUUCAGAGAAUUUGUCUUAU 21

Intron2-3490 18590

CFTR-

- GGUUUCAGAGAAUUUGUCUUAU 22

lntron2-3491 18591

CFTR-

- UGGUUUCAGAGAAUUUGUCUUAU 23

lntron2-3492 18592

CFTR-

- UUGGUUUCAGAGAAUUUGUCUUAU 24

lntron2-3493 18593

CFTR-

- UUUGUACCUCUGCACCCU 18

lntron2-3494 18594

CFTR-

- CUUUGUACCUCUGCACCCU 19

lntron2-3495 18595

CFTR-

- ACUUUGUACCUCUGCACCCU 20

Intron2-705 15805

CFTR-

- UACUUUGUACCUCUGCACCCU 21

lntron2-3496 18596

CFTR-

- GUACUUUGUACCUCUGCACCCU 22

lntron2-3497 18597

CFTR-

- GGUACUUUGUACCUCUGCACCCU 23

lntron2-3498 18598

CFTR-

- UGGUACUUUGUACCUCUGCACCCU 24

lntron2-3499 18599

CFTR-

- AAUACAAAUGUACUCCCU 18

Intron2-3500 18600

CFTR-

- GAAUACAAAUGUACUCCCU 19

Intron2-3501 18601

CFTR-

- UGAAUACAAAUGUACUCCCU 20

lntron2-389 15489

CFTR-

- UUGAAUACAAAUGUACUCCCU 21

Intron2-3502 18602

CFTR-

- UUUGAAUACAAAUGUACUCCCU 22

Intron2-3503 18603

CFTR-

- AUUUGAAUACAAAUGUACUCCCU 23

Intron2-3504 18604

CFTR-

- UAUUUGAAUACAAAUGUACUCCCU 24

Intron2-3505 18605

CFTR-

- UAGGUGGAGAACUGGCCU 18

Intron2-3506 18606

593

5535.1 CFTR-

- CUAGGUGGAGAACUGGCCU 19

Intron2-3507 18607

CFTR-

- CCUAGGUGGAGAACUGGCCU 20

Intron2-3508 18608

CFTR-

- ACCUAGGUGGAGAACUGGCCU 21

Intron2-3509 18609

CFTR-

- GACCUAGGUGGAGAACUGGCCU 22

Intron2-3510 18610

CFTR-

- AGACCUAGGUGGAGAACUGGCCU 23

lntron2-3511 18611

CFTR-

- AAGACCUAGGUGGAGAACUGGCCU 24

lntron2-3512 18612

CFTR-

- GAAAAG CAAAC U G AG G C U 18

lntron2-3513 18613

CFTR-

- AG AAAAG CAAAC U GAG G C U 19

lntron2-3514 18614

CFTR-

- CAGAAAAG CAAAC U GAG G C U 20

lntron2-3515 18615

CFTR-

- A C AG AAAAG C A A AC U G AG G C U 21

lntron2-3516 18616

CFTR-

- U A C AG AAAAG C A A AC U G AG G C U 22

lntron2-3517 18617

CFTR-

- U U AC AG AAAAG C A A AC U G AG G C U 23

lntron2-3518 18618

CFTR-

- UUUACAGAAAAGCAAACUGAGGCU 24

lntron2-3519 18619

CFTR-

- GAUGCCAAGAUCCAUGCU 18

Intron2-3520 18620

CFTR-

- GGAUGCCAAGAUCCAUGCU 19

lntron2-3521 18621

CFTR-

- GGGAUGCCAAGAUCCAUGCU 20

lntron2-3522 18622

CFTR-

- GGGGAUGCCAAGAUCCAUGCU 21

lntron2-3523 18623

CFTR-

- AGGGGAUGCCAAGAUCCAUGCU 22

lntron2-3524 18624

CFTR-

- UAGGGGAUGCCAAGAUCCAUGCU 23

lntron2-3525 18625

CFTR-

- CUAGGGGAUGCCAAGAUCCAUGCU 24

lntron2-3526 18626

CFTR-

- AAGUUUUAAUUGGAUGCU 18

lntron2-3527 18627

594

5535.1 CFTR-

- UAAGUUUUAAUUGGAUGCU 19

lntron2-3528 18628

CFTR-

- CUAAGUUUUAAUUGGAUGCU 20

lntron2-3529 18629

CFTR-

- UCUAAGUUUUAAUUGGAUGCU 21

Intron2-3530 18630

CFTR-

- AUCUAAGUUUUAAUUGGAUGCU 22

lntron2-3531 18631

CFTR-

- UAUCUAAGUUUUAAUUGGAUGCU 23

lntron2-3532 18632

CFTR-

- AUAUCUAAGUUUUAAUUGGAUGCU 24

lntron2-3533 18633

CFTR-

- UCUCAUUAGCAAGCUUCU 18

lntron2-3534 18634

CFTR-

- CUCUCAUUAGCAAGCUUCU 19

lntron2-3535 18635

CFTR-

- GCUCUCAUUAGCAAGCUUCU 20

lntron2-75 15175

CFTR-

- GGCUCUCAUUAGCAAGCUUCU 21

lntron2-3536 18636

CFTR-

- GGGCUCUCAUUAGCAAGCUUCU 22

lntron2-3537 18637

CFTR-

- AGGGCUCUCAUUAGCAAGCUUCU 23

lntron2-3538 18638

CFTR-

- AAGGGCUCUCAUUAGCAAGCUUCU 24

lntron2-3539 18639

CFTR-

- UUUUCAUCUCUGUACAGU 18

Intron2-3540 18640

CFTR-

- UUUUUCAUCUCUGUACAGU 19

lntron2-3541 18641

CFTR-

- AUUUUUCAUCUCUGUACAGU 20

lntron2-3542 18642

CFTR-

- AAUUUUUCAUCUCUGUACAGU 21

lntron2-3543 18643

CFTR-

- AAAUUUUUCAUCUCUGUACAGU 22

lntron2-3544 18644

CFTR-

- GAAAUUUUUCAUCUCUGUACAGU 23

lntron2-3545 18645

CFTR-

- UGAAAUUUUUCAUCUCUGUACAGU 24

lntron2-3546 18646

CFTR-

- UUUCUACAUUACUUCCGU 18

lntron2-3547 18647

595

5535.1 CFTR-

- CUUUCUACAUUACUUCCGU 19

lntron2-3548 18648

CFTR-

- CCUUUCUACAUUACUUCCGU 20

lntron2-3549 18649

CFTR-

- ACCUUUCUACAUUACUUCCGU 21

Intron2-3550 18650

CFTR-

- CACCUUUCUACAUUACUUCCGU 22

lntron2-3551 18651

CFTR-

- ACACCUUUCUACAUUACUUCCGU 23

lntron2-3552 18652

CFTR-

- AACACCUUUCUACAUUACUUCCGU 24

lntron2-3553 18653

CFTR-

- AAUGCUGGGAUUAUAGGU 18

lntron2-3554 18654

CFTR-

- AAAUGCUGGGAUUAUAGGU 19

lntron2-3555 18655

CFTR-

- AAAAUGCUGGGAUUAUAGGU 20

lntron2-3556 18656

CFTR-

- CAAAAUGCUGGGAUUAUAGGU 21

lntron2-3557 18657

CFTR-

- CCAAAAUGCUGGGAUUAUAGGU 22

lntron2-3558 18658

CFTR-

- CCCAAAAUGCUGGGAUUAUAGGU 23

lntron2-3559 18659

CFTR-

- UCCCAAAAUGCUGGGAUUAUAGGU 24

Intron2-3560 18660

CFTR-

- AUAAAGUGGGUCCCUGGU 18

lntron2-3561 18661

CFTR-

- CAUAAAGUGGGUCCCUGGU 19

lntron2-3562 18662

CFTR-

- ACAUAAAGUGGGUCCCUGGU 20

lntron2-3563 18663

CFTR-

- UACAUAAAGUGGGUCCCUGGU 21

lntron2-3564 18664

CFTR-

- CUACAUAAAGUGGGUCCCUGGU 22

lntron2-3565 18665

CFTR-

- UCUACAUAAAGUGGGUCCCUGGU 23

lntron2-3566 18666

CFTR-

- UUCUACAUAAAGUGGGUCCCUGGU 24

lntron2-3567 18667

CFTR-

- AAAGGUGGAGAAGCAUGU 18

lntron2-3568 18668

596

5535.1 CFTR-

- GAAAGGUGGAGAAGCAUGU 19

lntron2-3569 18669

CFTR-

- AG A A AG GUGGAGAAGCAUGU 20

Intron2-406 15506

CFTR-

- GAGAAAGGUGGAGAAGCAUGU 21

Intron2-3570 18670

CFTR-

- AGAGAAAGGUGGAGAAGCAUGU 22

lntron2-3571 18671

CFTR-

- GAGAGAAAGGUGGAGAAGCAUGU 23

lntron2-3572 18672

CFTR-

- UGAGAGAAAGGUGGAGAAGCAUGU 24

lntron2-3573 18673

CFTR-

- GGGAGGUUAGCUCUGUGU 18

lntron2-3574 18674

CFTR-

- UGGGAGGUUAGCUCUGUGU 19

lntron2-3575 18675

CFTR-

- AUGGGAGGUUAGCUCUGUGU 20

lntron2-3576 18676

CFTR-

- GAUGGGAGGUUAGCUCUGUGU 21

lntron2-3577 18677

CFTR-

- GGAUGGGAGGUUAGCUCUGUGU 22

lntron2-3578 18678

CFTR-

- UGGAUGGGAGGUUAGCUCUGUGU 23

lntron2-3579 18679

CFTR-

- AUGGAUGGGAGGUUAGCUCUGUGU 24

Intron2-3580 18680

CFTR-

- GAGGUUAGCUCUGUGUGU 18

lntron2-3581 18681

CFTR-

- GGAGGUUAGCUCUGUGUGU 19

lntron2-3582 18682

CFTR-

- GGGAGGUUAGCUCUGUGUGU 20

lntron2-3583 18683

CFTR-

- UGGGAGGUUAGCUCUGUGUGU 21

lntron2-3584 18684

CFTR-

- AUGGGAGGUUAGCUCUGUGUGU 22

lntron2-3585 18685

CFTR-

- GAUGGGAGGUUAGCUCUGUGUGU 23

lntron2-3586 18686

CFTR-

- GGAUGGGAGGUUAGCUCUGUGUGU 24

lntron2-3587 18687

CFTR-

- AACUAAAGUAACACCAUU 18

lntron2-3588 18688

597

5535.1 CFTR-

- AAACU AAAG U AACACCAU U 19

lntron2-3589 18689

CFTR-

- AAAACUAAAGUAACACCAUU 20

Intron2-3590 18690

CFTR-

- G AAAACU AAAG U AACACCAU U 21

lntron2-3591 18691

CFTR-

- UG AAAACU AAAG U AACACCAU U 22

lntron2-3592 18692

CFTR-

- G UG AAAACU AAAG U AACACCAU U 23

lntron2-3593 18693

CFTR-

- UG UG AAAACU AAAG U AACACCAU U 24

lntron2-3594 18694

CFTR-

- UUUCCUUUUUUUGGCAUU 18

lntron2-3595 18695

CFTR-

- AUUUCCUUUUUUUGGCAUU 19

lntron2-3596 18696

CFTR-

- CAUUUCCUUUUUUUGGCAUU 20

lntron2-3597 18697

CFTR-

- UCAUUUCCUUUUUUUGGCAUU 21

lntron2-3598 18698

CFTR-

- UUCAUUUCCUUUUUUUGGCAUU 22

lntron2-3599 18699

CFTR-

- AUUCAUUUCCUUUUUUUGGCAUU 23

Intron2-3600 18700

CFTR-

- AAUUCAUUUCCUUUUUUUGGCAUU 24

Intron2-3601 18701

CFTR-

- UACUCCUUUAGAGUGAUU 18

Intron2-3602 18702

CFTR-

- UUACUCCUUUAGAGUGAUU 19

Intron2-3603 18703

CFTR-

- AUUACUCCUUUAGAGUGAUU 20

Intron2-3604 18704

CFTR-

- UAUUACUCCUUUAGAGUGAUU 21

Intron2-3605 18705

CFTR-

- CUAUUACUCCUUUAGAGUGAUU 22

Intron2-3606 18706

CFTR-

- CCUAUUACUCCUUUAGAGUGAUU 23

Intron2-3607 18707

CFTR-

- GCCUAUUACUCCUUUAGAGUGAUU 24

Intron2-3608 18708

CFTR-

- GAAAUUUAUUGAAAUAUU 18

Intron2-3609 18709

598

5535.1 CFTR-

- UGAAAUUUAUUGAAAUAUU 19

Intron2-3610 18710

CFTR-

- UUGAAAUUUAUUGAAAUAUU 20

lntron2-3611 18711

CFTR-

- UUUGAAAUUUAUUGAAAUAUU 21

lntron2-3612 18712

CFTR-

- AUUUGAAAUUUAUUGAAAUAUU 22

lntron2-3613 18713

CFTR-

- UAUUUGAAAUUUAUUGAAAUAUU 23

lntron2-3614 18714

CFTR-

- GUAUUUGAAAUUUAUUGAAAUAUU 24

lntron2-3615 18715

CFTR-

- AAUUAAGAUGAUAAUAUU 18

lntron2-3616 18716

CFTR-

- AAAUUAAGAUGAUAAUAUU 19

lntron2-3617 18717

CFTR-

- AAAAUUAAGAUGAUAAUAUU 20

lntron2-3618 18718

CFTR-

- GAAAAUUAAGAUGAUAAUAUU 21

lntron2-3619 18719

CFTR-

- UGAAAAUUAAGAUGAUAAUAUU 22

Intron2-3620 18720

CFTR-

- U U GAAAAU U AAG AUG AU AAU AU U 23

lntron2-3621 18721

CFTR-

- UUUGAAAAUUAAGAUGAUAAUAUU 24

lntron2-3622 18722

CFTR-

- UUGUACCUCUGCACCCUU 18

lntron2-3623 18723

CFTR-

- UUUGUACCUCUGCACCCUU 19

lntron2-3624 18724

CFTR-

- CUUUGUACCUCUGCACCCUU 20

lntron2-412 15512

CFTR-

- ACUUUGUACCUCUGCACCCUU 21

lntron2-3625 18725

CFTR-

- UACUUUGUACCUCUGCACCCUU 22

lntron2-3626 18726

CFTR-

- GUACUUUGUACCUCUGCACCCUU 23

lntron2-3627 18727

CFTR-

- GGUACUUUGUACCUCUGCACCCUU 24

lntron2-3628 18728

CFTR-

- AGGUGGAGAACUGGCCUU 18

lntron2-3629 18729

599

5535.1 CFTR-

- UAGGUGGAGAACUGGCCUU 19

Intron2-3630 18730

CFTR-

- CUAGGUGGAGAACUGGCCUU 20

lntron2-414 15514

CFTR-

- CCUAGGUGGAGAACUGGCCUU 21

lntron2-3631 18731

CFTR-

- ACCUAGGUGGAGAACUGGCCUU 22

lntron2-3632 18732

CFTR-

- GACCUAGGUGGAGAACUGGCCUU 23

lntron2-3633 18733

CFTR-

- AGACCUAGGUGGAGAACUGGCCUU 24

lntron2-3634 18734

CFTR-

- GGUCACUAGAGACCUCUU 18

lntron2-3635 18735

CFTR-

- GGGUCACUAGAGACCUCUU 19

lntron2-3636 18736

CFTR-

- AGGGUCACUAGAGACCUCUU 20

lntron2-3637 18737

CFTR-

- CAGGGUCACUAGAGACCUCUU 21

lntron2-3638 18738

CFTR-

- CCAGGGUCACUAGAGACCUCUU 22

lntron2-3639 18739

CFTR-

- CCCAGGGUCACUAGAGACCUCUU 23

Intron2-3640 18740

CFTR-

- GCCCAGGGUCACUAGAGACCUCUU 24

lntron2-3641 18741

CFTR-

- AAAUUUAUUGAAAUAUUU 18

lntron2-3642 18742

CFTR-

- GAAAUUUAUUGAAAUAUUU 19

lntron2-3643 18743

CFTR-

- UGAAAUUUAUUGAAAUAUUU 20

lntron2-721 15821

CFTR-

- U U GAAAU U U AU UG AAAU AU U U 21

lntron2-3644 18744

CFTR-

- UUUGAAAUUUAUUGAAAUAUUU 22

lntron2-3645 18745

CFTR-

- AUUUGAAAUUUAUUGAAAUAUUU 23

lntron2-3646 18746

CFTR-

- UAUUUGAAAUUUAUUGAAAUAUUU 24

lntron2-3647 18747

CFTR-

- GAGAUAUUUUAUUCCUUU 18

lntron2-3648 18748

600

5535.1 CFTR-

- AGAGAUAUUUUAUUCCUUU 19

lntron2-3649 18749

CFTR-

- UAGAGAUAUUUUAUUCCUUU 20

Intron2-3650 18750

CFTR-

- UUAGAGAUAUUUUAUUCCUUU 21

lntron2-3651 18751

CFTR-

- UUUAGAGAUAUUUUAUUCCUUU 22

lntron2-3652 18752

CFTR-

- AUUUAGAGAUAUUUUAUUCCUUU 23

lntron2-3653 18753

CFTR-

- UAUUUAGAGAUAUUUUAUUCCUUU 24

lntron2-3654 18754

CFTR-

- CUCUUUGCUCCUAUCUUU 18

lntron2-3655 18755

CFTR-

- ACUCUUUGCUCCUAUCUUU 19

lntron2-3656 18756

CFTR-

- AACUCUUUGCUCCUAUCUUU 20

lntron2-3657 18757

CFTR-

- GAACUCUUUGCUCCUAUCUUU 21

lntron2-3658 18758

CFTR-

- AGAACUCUUUGCUCCUAUCUUU 22

lntron2-3659 18759

CFTR-

- UAGAACUCUUUGCUCCUAUCUUU 23

Intron2-3660 18760

CFTR-

- UUAGAACUCUUUGCUCCUAUCUUU 24

lntron2-3661 18761

CFTR-

- AAAAU ACACAU U UGG U U U 18

lntron2-3662 18762

CFTR-

- AAAAAUACACAUUUGGUUU 19

lntron2-3663 18763

CFTR-

- GAAAAAUACACAUUUGGUUU 20

lntron2-3664 18764

CFTR-

- UGAAAAAUACACAUUUGGUUU 21

lntron2-3665 18765

CFTR-

- CUG AAAAAU ACACAU U U GG U U U 22

lntron2-3666 18766

CFTR-

- CCUG AAAAAU ACACAU U UGG U U U 23

lntron2-3667 18767

CFTR-

- U CCUG AAAAAU ACACAU U UGG U U U 24

lntron2-3668 18768

CFTR-

- UUGUUGUUGCUGUUGUUU 18

lntron2-3669 18769

601

5535.1 CFTR-

- GUUGUUGUUGCUGUUGUUU 19

Intron2-3670 18770

CFTR-

- UGUUGUUGUUGCUGUUGUUU 20

lntron2-3671 18771

CFTR-

- UUGUUGUUGUUGCUGUUGUUU 21

lntron2-3672 18772

CFTR-

- GUUGUUGUUGUUGCUGUUGUUU 22

lntron2-3673 18773

CFTR-

- UGUUGUUGUUGUUGCUGUUGUUU 23

lntron2-3674 18774

CFTR-

- UUGUUGUUGUUGUUGCUGUUGUUU 24

lntron2-3675 18775

CFTR-

- UGUUUGUGUUGUUUGUUU 18

lntron2-3676 18776

CFTR-

- UUGUUUGUGUUGUUUGUUU 19

lntron2-3677 18777

CFTR-

- UUUGUUUGUGUUGUUUGUUU 20

lntron2-3678 18778

CFTR-

- GUUUGUUUGUGUUGUUUGUUU 21

lntron2-3679 18779

CFTR-

- UGUUUGUUUGUGUUGUUUGUUU 22

Intron2-3680 18780

CFTR-

- UUGUUUGUUUGUGUUGUUUGUUU 23

lntron2-3681 18781

CFTR-

- UUUGUUUGUUUGUGUUGUUUGUUU 24

lntron2-3682 18782

CFTR-

- GACCAUGAGAUGGAUUUU 18

lntron2-3683 18783

CFTR-

- AGACCAUGAGAUGGAUUUU 19

lntron2-3684 18784

CFTR-

- GAGACCAUGAGAUGGAUUUU 20

lntron2-3685 18785

CFTR-

- AGAGACCAUGAGAUGGAUUUU 21

lntron2-3686 18786

CFTR-

- UAGAGACCAUGAGAUGGAUUUU 22

lntron2-3687 18787

CFTR-

- UU AGAGACCAUGAGAUGGAUUUU 23

lntron2-3688 18788

CFTR-

- AUUAGAGACCAUGAGAUGGAUUUU 24

lntron2-3689 18789

602

5535.1 Table 39A provides exemplary targeting domains for correcting a mutation (e.g., 3272- 26->G) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within intron 2, have a high level of orthogonality and start with a 5'G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 39A

603

5535.1 Table 39B provides exemplary targeting domains for correcting a mutation (e.g., 3272- 26->G) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within intron 2 and have a high level of orthogonality. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 39B

604

5535.1 CFTR-lntron2-

+ AAAGGAGUAAUACACAG 17

3716 18816

CFTR-lntron2-

- CACU U CU AAG AU CAAGG 17

3717 18817

CFTR-lntron2-

- UUAAUUGGAUGCUGAGG 17

3718 18818

CFTR-lntron2-

- UUAUUUUCUCAGACCGG 17

3719 18819

CFTR-lntron2-

- UCCAUGCUUAGAGAUUG 17

3720 18820

CFTR-lntron2-

- U U U CAAAG ACCU UUAAU 17

3721 18821

CFTR-lntron2-

- CUAGGGGAUGCCAAGAU 17

3722 18822

CFTR-lntron2-

- UGAAGUAAAUCGUGUAU 17

3723 18823

CFTR-lntron2-

+ UGAUUGGAAAGGAAACU 17

3724 18824

CFTR-lntron2-

- AUGCCAAGAUCCAUGCU 17

3725 18825

CFTR-lntron2-

- AUUAAGCUAGUGGGAGU 17

3726 18826

CFTR-lntron2-

+ CUAGGUCUUCACAUAGU 17

3727 18827

CFTR-lntron2-

- CAAACCACACAUCCGUU 17

3728 18828

CFTR-lntron2-

- AAAUAGAUGGGAAAAGGUAA 20

3729 18829

CFTR-lntron2-

- AGUUUUCACUGUAUCCCCCA 20

3730 18830

CFTR-lntron2-

- UCCCAGAGACUCUUGAGUCA 20

3731 18831

CFTR-lntron2-

- UGUCUUAUUAGAGACCAUGA 20

3732 18832

CFTR-lntron2-

+ UUUCAAUUAACCCAGCCCUA 20

3733 18833

CFTR-lntron2-

- AAUCUGAAUUUGCAGAAUUA 20

3734 18834

CFTR-lntron2-

- CCCGGCCUAUUACUCCUUUA 20

3735 18835

CFTR-lntron2-

+ AACU AGG U AAACAAU U AG AC 20

3736 18836

605

5535.1 CFTR-lntron2-

- CUGCACCCUUGGGAAGUGAC 20

3737 18837

CFTR-lntron2-

- AUCUGGCUCAAUUUUGUGAC 20

3738 18838

CFTR-lntron2-

+ CAAUCAAAAGGAUCCUAACC 20

3739 18839

CFTR-lntron2-

+ U U AAAU ACU AU AGGAACACC 20

3740 18840

CFTR-lntron2-

+ AGUGUGAAUCUGCUACUCCC 20

3741 18841

CFTR-lntron2-

- CAAUCAAAAGGUUAGGAUCC 20

3742 18842

CFTR-lntron2-

+ CAUAAAGGAGUAAUACACAG 20

2142 17242

CFTR-lntron2-

- UCACACUUCUAAGAUCAAGG 20

3743 18843

CFTR-lntron2-

+ CUAGCCAUUUCACAUUCCAU 20

3744 18844

CFTR-lntron2-

- CUUCUAGGGGAUGCCAAGAU 20

3745 18845

CFTR-lntron2-

+ UUUUGAUUGGAAAGGAAACU 20

2486 17586

CFTR-lntron2-

+ CAUGGAUCUUGGCAUCCCCU 20

3746 18846

CFTR-lntron2-

- AGAAUUAAGCUAGUGGGAGU 20

3747 18847

CFTR-lntron2-

+ CACCUAGGUCUUCACAUAGU 20

3748 18848

CFTR-lntron2-

+ UUUGCACACUGCAGUUAUGU 20

3749 18849

CFTR-lntron2-

- CAGUGACAGAAACCCAAUUU 20

3750 18850

Table 39C provides exemplary targeting domains for correcting a mutation (e.g., 3272- 26->G) in the CFTR gene selected according to the third tier parameters. The targeting domains bind within intron 2 and start with a 5'G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 39C

606

5535.1 3rd Tier

Target Site

gRNA Name DNA Strand Targeting Domain

Length Seq ID

CFTR-lntron2-

- GUUAAUGAAUGAUGGAG 17

3751 18851

CFTR-lntron2-

+ GCCAUUUCACAUUCCAU 17

3752 18852

Table 39D provides exemplary targeting domains for correcting a mutation (e.g., 3272- 26->G) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within intron 2. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 39D

607

5535.1 CFTR-lntron2-

- AGGUGUGAGCCACUAUG 17

3764 18864

CFTR-lntron2-

- CUUGGCCUCCCAAAGUG 17

3765 18865

CFTR-lntron2-

+ CUAUGACUCAAGAGUCU 17

3766 18866

CFTR-lntron2-

- UG ACAG AAACCCAAU U U 17

3767 18867

CFTR-lntron2-

- AAG AAAACAG AAAG U U U 17

3768 18868

CFTR-lntron2-

- AUAUUAAACUUUAUUUU 17

3769 18869

CFTR-lntron2-

+ AAGCCAGAUAAUUCUGCAAA 20

3770 18870

CFTR-lntron2-

- UAUUCCUUUGUGAAGAGAAA 20

3771 18871

CFTR-lntron2-

+ U U U CUG U AAAAU AG AG AU AA 20

3772 18872

CFTR-lntron2-

+ UAUUAUCUCUCUGAGCCUCA 20

3773 18873

CFTR-lntron2-

+ AGUCCCAGCUACUCAGGAGA 20

1715 16815

CFTR-lntron2-

- UUAUAGAAGGGCUCUCAUUA 20

3774 18874

CFTR-lntron2-

+ UCCCAUCUAUUUCCCUCCCC 20

3775 18875

CFTR-lntron2-

+ UGUAUUUAUUAAGUUAUUGC 20

3776 18876

CFTR-lntron2-

- AAACUUCGUCUCCUGGGUUC 20

3777 18877

CFTR-lntron2-

- CCAGUUAAUGAAUGAUGGAG 20

3778 18878

CFTR-lntron2-

+ CAGCUACUCAGGAGACUGAG 20

3779 18879

CFTR-lntron2-

- CACCUUGGCCUCCCAAAAUG 20

3291 18391

CFTR-lntron2-

- UAUAGGUGUGAGCCACUAUG 20

3780 18880

CFTR-lntron2-

- CGCCUUGGCCUCCCAAAGUG 20

3352 18452

CFTR-lntron2-

- AGAUCCAUGCUUAGAGAUUG 20

3781 18881

608

5535.1 CFTR-lntron2-

- AUUUUUCAAAGACCUUUAAU 20

3782 18882

CFTR-lntron2-

+ AAGGUUUUGAAAGCAAAUAU 20

3783 18883

CFTR-lntron2-

- UUAUGAAGUAAAUCGUGUAU 20

3784 18884

CFTR-lntron2-

- U AAAAG AAAACAG AAAG U U U 20

3785 18885

CFTR-lntron2-

- AAGAUAUUAAACUUUAUUUU 20

3786 18886

Table 40A provides exemplary targeting domains for correcting a mutation (e.g., 3272- 26->G) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within intron 10, have a high level of orthogonality and start with a 5'G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 40A

609

5535.1 9

CFTR-lntronlO-

- GUGCCACUAGUGAUGCA 17

10 18896

CFTR-lntronlO-

- GUACAAGUCUAGUUUCA 17

11 18897

CFTR-lntronlO-

- GGCUGGUAGUGUGAAGA 17

12 18898

CFTR-lntronlO-

+ GUGAUGCAGACAACAGA 17

13 18899

CFTR-lntronlO-

+ GACUAAAACUGAGUAGA 17

14 18900

CFTR-lntronlO-

+ GGUACAAAUUUCAGGGA 17

15 18901

CFTR-lntronlO-

+ GUCUCUCUAAGGUGUGA 17

16 18902

CFTR-lntronlO-

+ GUUCUUAGGGUGGGAUA 17

17 18903

CFTR-lntronlO-

- GUGUAGGGGUUAGCCUA 17

18 18904

CFTR-lntronlO-

+ GCCUAUCACCUAGGCUA 17

19 18905

CFTR-lntronlO-

+ GUGUGAGGGUCUCUCUA 17

20 18906

CFTR-lntronlO-

- GACUGAAAGCUGGCUUA 17

21 18907

CFTR-lntronlO-

+ G U AUG U AGG AAAACAAC 17

22 18908

CFTR-lntronlO-

+ GUAUUAAGUAUAGCCAC 17

23 18909

CFTR-lntronlO-

- GUGAGAUUAGAGGCCAC 17

24 18910

CFTR-lntronlO-

- GAUGAGCAGAUAAUUAC 17

25 18911

CFTR-lntronlO-

+ GUAUCUCCAAAUAUGCC 17

26 18912

CFTR-lntronlO-

- GAAUGAAUGUGGUAUCC 17

27 18913

CFTR-lntronlO-

+ GACAUCAGUUGGGUUCC 17

28 18914

CFTR-lntronlO-

+ GUUGGAUGAGGGAAUGC 17

29 18915

CFTR-lntronlO-

+ GCUAUUUAAACAGAAUC 17

30 18916

610

5535.1 CFTR-lntronlO-

- GACUGACUAUACCUGUC 17

31 18917

CFTR-lntronlO-

- GUCUAUUGUGCCAGUUC 17

32 18918

CFTR-lntronlO-

+ GAAUUGG UACAAAU U U C 17

33 18919

CFTR-lntronlO-

- GAUGAUUCCAAGCU UUC 17

34 18920

CFTR-lntronlO-

+ GAUAUCUUAGGUCAAAG 17

35 18921

CFTR-lntronlO-

- GUCUAGUUUCAAGGAAG 17

36 18922

CFTR-lntronlO-

+ GCUAAAGUAUUACCCAG 17

37 18923

CFTR-lntronlO-

- GGCAUUCUAAGUAUUAG 17

38 18924

CFTR-lntronlO-

- GUCAGAGAAGUAAUCGG 17

39 18925

CFTR-lntronlO-

- GAAGUAAUCGGCGGUGG 17

40 18926

CFTR-lntronlO-

+ GCUACCUUGGUUGGAUG 17

41 18927

CFTR-lntronlO-

- GAUUGUCAUUUUAGCUG 17

42 18928

CFTR-lntronlO-

+ GAAAUGGGGUAUAAGUG 17

43 18929

CFTR-lntronlO-

- GAUGGUAUUGCAGGGUG 17

44 18930

CFTR-lntronlO-

- GAGCCAAAAAUUGGGUG 17

45 18931

CFTR-lntronlO-

- GGCAUCUCACCAGUGUG 17

46 18932

CFTR-lntronlO-

+ GGUCUCUCUAAGGUGUG 17

47 18933

CFTR-lntronlO-

- GGUAAGCUCAAGCAUUG 17

48 18934

CFTR-lntronlO-

- GUAUUUACCAUAUAUUG 17

49 18935

CFTR-lntronlO-

- GGUUUCCACUCAACAAU 17

50 18936

CFTR-lntronlO-

- GCUGGUAGUGUGAAGAU 17

51 18937

CFTR-lntronlO- - GUGCAAAGCUUUCAGAU 17 18938

611

5535.1 52

CFTR-lntronlO-

- GAAGGGUGUUAUCAACU 17

53 18939

CFTR-lntronlO-

- GAAUUGAAUAUGAGACU 17

54 18940

CFTR-lntronlO-

- GGAAGGCAGUGGUCCCU 17

55 18941

CFTR-lntronlO-

- GUGAAAAUAUCACUUCU 17

56 18942

CFTR-lntronlO-

- GGAGCCAAAAAUUGGGU 17

57 18943

CFTR-lntronlO-

+ GGAUUGGCUACCUUGGU 17

58 18944

CFTR-lntronlO-

- GUCACUGUAUUGUCUGU 17

59 18945

CFTR-lntronlO-

- GCAUCUCACCAGUGUGU 17

60 18946

CFTR-lntronlO-

+ GAAG U AG AAG AACU AU U 17

61 18947

CFTR-lntronlO-

+ GUUUGUCUUAGAUUAU U 17

62 18948

CFTR-lntronlO-

- GAUUAGCUUAUAUACU U 17

63 18949

CFTR-lntronlO-

- GAAGGCAGUGGUCCCUU 17

64 18950

CFTR-lntronlO-

+ GAGUGCAUAAAGGUUGAAAA 20

65 18951

CFTR-lntronlO-

- GCUAUUCUGUAGGGAGACAA 20

66 18952

CFTR-lntronlO-

- GAUACUAAAUAAGUUAGCAA 20

67 18953

CFTR-lntronlO-

- GAGGGUUGAUAAGAAGAGAA 20

68 18954

CFTR-lntronlO-

- GCCGUUUACUAGAAAGAUAA 20

69 18955

CFTR-lntronlO-

- GGGUGUAGGGGUUAGCCUAA 20

70 18956

CFTR-lntronlO-

- GGGGCUGGAUAAGAUUCUAA 20

71 18957

CFTR-lntronlO-

+ GGUAUAAGUGUGGAGUGUAA 20

72 18958

CFTR-lntronlO-

- GGAAGAUCCAAUAGGAUUAA 20

73 18959

612

5535.1 CFTR-lntronlO-

- GGCUGGCAUAGAGUAAGACA 20

74 18960

CFTR-lntronlO-

- GGCUAUUCUGUAGGGAGACA 20

75 18961

CFTR-lntronlO-

+ GAAGUGUUUAAAUAUUCCCA 20

76 18962

CFTR-lntronlO-

+ GUGCUAUUUAAACAGAAUCA 20

77 18963

CFTR-lntronlO-

+ GGAUUGCUUGAUGUUAUUCA 20

78 18964

CFTR-lntronlO-

- GAUGUACAAGUCUAGUUUCA 20

79 18965

CFTR-lntronlO-

- GGGGGCUGGUAGUGUGAAGA 20

80 18966

CFTR-lntronlO-

+ GCUGUGAUGCAGACAACAGA 20

81 18967

CFTR-lntronlO-

- G C A AG U G C A A AG CUUUCAGA 20

82 18968

CFTR-lntronlO-

- GGCAUAGAGUAAGACAGGGA 20

83 18969

CFTR-lntronlO-

+ GUUGUUCUUAGGGUGGGAUA 20

84 18970

CFTR-lntronlO-

- GGGGUGUAGGGGUUAGCCUA 20

85 18971

CFTR-lntronlO-

- GUCUGGUUUGAAGAACAGUA 20

86 18972

CFTR-lntronlO-

+ GCCAGGUUAAGUUGUUCUUA 20

87 18973

CFTR-lntronlO-

- GAG U U U U AAACAG AAG U AAC 20

88 18974

CFTR-lntronlO-

+ GACUGAAACUCCCCACACAC 20

89 18975

CFTR-lntronlO-

+ GCUAAGAGACUCCUGAAUCC 20

90 18976

CFTR-lntronlO-

+ GU UUUAGUAGAAACCUAAUC 20

91 18977

CFTR-lntronlO-

- GGAUUAGGGAAUGCAGACUC 20

92 18978

CFTR-lntronlO-

- GGAGUCUAUUGUGCCAGUUC 20

93 18979

CFTR-lntronlO-

+ GCUUGACAUCAGUUGGGUUC 20

94 18980

CFTR-lntronlO- - GAUAAGAUUCU A A AG G A A AG 20 18981

613

5535.1 95

CFTR-lntronlO-

+ GGGUCAAUUGUAUUAGCAAG 20

96 18982

CFTR-lntronlO-

+ GGCU UAACCCAUCUAUUAAG 20

97 18983

CFTR-lntronlO-

+ GCAUAUUGGACCAGACACAG 20

98 18984

CFTR-lntronlO-

- GCAUAUGAGAAAAGUCACAG 20

99 18985

CFTR-lntronlO-

+ GCCUAGAUGAUUAUUAAUAG 20

100 18986

CFTR-lntronlO-

- GUAAUCGGCGGUGGAGGUAG 20

101 18987

CFTR-lntronlO-

+ GAUCAAUAAUAGAGACAAGG 20

102 18988

CFTR-lntronlO-

- GUCUAGUUUCAAGGAAGAGG 20

103 18989

CFTR-lntronlO-

- GU UUACUAACUCAAUCUAGG 20

104 18990

CFTR-lntronlO-

- GUCAGAGAAGUAAUCGGCGG 20

105 18991

CFTR-lntronlO-

- GGGCUGGUAGUGUGAAGAUG 20

106 18992

CFTR-lntronlO-

+ G U U ACAU AAAAAG AG AGG UG 20

107 18993

CFTR-lntronlO-

+ GAGGGUCUCUCUAAGGUGUG 20

108 18994

CFTR-lntronlO-

- GCUU UGAAGGAAGAUCCAAU 20

109 18995

CFTR-lntronlO-

- GAGCU UUCUAGUAUUAGAAU 20

110 18996

CFTR-lntronlO-

- GGGGCUGGUAGUGUGAAGAU 20

111 18997

CFTR-lntronlO-

- GUCU UUUCCUCUUAAUAGAU 20

112 18998

CFTR-lntronlO-

- GCAGAAGGGUGUUAUCAACU 20

113 18999

CFTR-lntronlO-

- GAAGAAUUGAAUAUGAGACU 20

114 19000

CFTR-lntronlO-

+ GU UACAACAGUCUUUAUACU 20

115 19001

CFTR-lntronlO-

+ GUUACCUGGAUUGGCUACCU 20

116 19002

614

5535.1 CFTR-lntronlO-

+ GU UACUCAGUCCAGAAAGCU 20

117 19003

CFTR-lntronlO-

- GGAGUUUACUAACUCAAUCU 20

118 19004

CFTR-lntronlO-

- GAUUAGGGAAUGCAGACUCU 20

119 19005

CFTR-lntronlO-

+ GGAAAGUUGUCCAAGAUAGU 20

120 19006

CFTR-lntronlO-

- GUAUUAGAGGUUAAGGAGGU 20

121 19007

CFTR-lntronlO-

- GGAAGCAGUGCUGCUGCUGU 20

122 19008

CFTR-lntronlO-

- GAAGUCACUGUAUUGUCUGU 20

123 19009

CFTR-lntronlO-

- GU UACCCAAUAAAAAAAAUU 20

124 19010

CFTR-lntronlO-

- GCUUUCAGGAG CCA A A A A U U 20

125 19011

CFTR-lntronlO-

- GGCUGCCUUUUAGUAGUAUU 20

126 19012

CFTR-lntronlO-

- GAGGAAGGCAGUGGUCCCUU 20

127 19013

CFTR-lntronlO-

- GU UUUGGAUGGAGCUUGGUU 20

128 19014

CFTR-lntronlO-

- GGGU UUGAUUAGAUAAAUUU 20

129 19015

CFTR-lntronlO-

- GUUGUUAUCUCUGAAAUUUU 20

130 19016

CFTR-lntronlO-

+ GGGCUCCCCCACCCAAUU UU 20

131 19017

Table 40B provides exemplary targeting domains for correcting a mutation (e.g., 3272- 26->G) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within intron 10 and have a high level of orthogonality. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through

complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 40B

615

5535.1 2nd Tier

Target Site

gRNA Name DNA Strand Targeting Domain

Length Seq ID

CFTR-lntronlO-

+ AGCUAUGCCCUUAAAAA 17

132 19018

CFTR-lntronlO-

- AUCAUCUAGGCUGCAAA 17

133 19019

CFTR-lntronlO-

- ACCUUCAUGUUGAUAAA 17

134 19020

CFTR-lntronlO-

+ UUCCUAAUACUACUAAA 17

135 19021

CFTR-lntronlO-

- UAUUAGAAUGGGCUAAA 17

136 19022

CFTR-lntronlO-

+ UCACGUGGUGUUUUAAA 17

137 19023

CFTR-lntronlO-

+ UACCAUUAUCUACACAA 17

138 19024

CFTR-lntronlO-

- AUUCUGUAGGGAGACAA 17

139 19025

CFTR-lntronlO-

- ACUAAAUAAG U UAGCAA 17

140 19026

CFTR-lntronlO-

+ AG CC AG CU U U CAG U CAA 17

141 19027

CFTR-lntronlO-

- UGUUGAUAAAGGGUCAA 17

142 19028

CFTR-lntronlO-

- ACUGAUGUCAAGCAGAA 17

143 19029

CFTR-lntronlO-

- UUUAGUAGUAUUAGGAA 17

144 19030

CFTR-lntronlO-

- UAAGAAAGACUCCUGAA 17

145 19031

CFTR-lntronlO-

+ A AG CAA AG AG U G C A U A A 17

146 19032

CFTR-lntronlO-

- ACCCAUUGUGUAGAUAA 17

147 19033

CFTR-lntronlO-

- AACCUUCAUGUUGAUAA 17

148 19034

CFTR-lntronlO-

- UUGGUGUAGUUCUAUAA 17

149 19035

CFTR-lntronlO-

- UGUAGGGGUUAGCCUAA 17

150 19036

CFTR-lntronlO-

+ AUAAGUGUGGAGUGUAA 17

151 19037

616

5535.1 CFTR-lntronlO-

- AGAUCCAAUAGGAUUAA 17

152 19038

CFTR-lntronlO-

+ UCAACUUUAUCUGUUAA 17

153 19039

CFTR-lntronlO-

+ UACCUUUCAAUGUUUAA 17

154 19040

CFTR-lntronlO-

- UAGCAAUGGUCUAAACA 17

155 19041

CFTR-lntronlO-

+ ACAAUCAAAUGGGAACA 17

156 19042

CFTR-lntronlO-

+ ACCUAUAAGGAAUAACA 17

157 19043

CFTR-lntronlO-

- UGGCAUAGAGUAAGACA 17

158 19044

CFTR-lntronlO-

- UAUUCUGUAGGGAGACA 17

159 19045

CFTR-lntronlO-

+ UUACAAUUCUUAUUACA 17

160 19046

CFTR-lntronlO-

- AUUCCCUCAUCCAACCA 17

161 19047

CFTR-lntronlO-

+ UAAAGACUUCACCCUCA 17

162 19048

CFTR-lntronlO-

+ AAGCCAGCUUUCAGUCA 17

163 19049

CFTR-lntronlO-

+ AUCUAAAAGCUAAUUCA 17

164 19050

CFTR-lntronlO-

+ UUGCUUGAUGU UAUUCA 17

165 19051

CFTR-lntronlO-

- UCUAGUUUCAAGGAAGA 17

166 19052

CFTR-lntronlO-

- AACUGAUGUCAAGCAGA 17

167 19053

CFTR-lntronlO-

- AG U G C A A AG C U U U C AG A 17

168 19054

CFTR-lntronlO-

+ ACCCUUUAUCAACAUGA 17

169 19055

CFTR-lntronlO-

+ CUACCUUGGUUGGAUGA 17

170 19056

CFTR-lntronlO-

- AUGAAAAGCAGCUAUGA 17

171 19057

CFTR-lntronlO-

- UUAAAGAAUGACUGUGA 17

172 19058

617

5535.1 CFTR-lntronlO-

- CGGUGUCU UCUGAAAUA 17

173 19059

CFTR-lntronlO-

+ CUAGAUGAUUAUUAAUA 17

174 19060

CFTR-lntronlO-

- ACUAAUUGUAGUACAUA 17

175 19061

CFTR-lntronlO-

+ AAAUUACAGAACCUAUA 17

176 19062

CFTR-lntronlO-

- UGAUCAUUGCCUCACUA 17

177 19063

CFTR-lntronlO-

- AGUGCUCGUAAAGACUA 17

178 19064

CFTR-lntronlO-

- UGACCUAAGAUAUCCUA 17

179 19065

CFTR-lntronlO-

- AAUCGGCGGUGGAGGUA 17

180 19066

CFTR-lntronlO-

+ ACUCUAUUUAGAGUGUA 17

181 19067

CFTR-lntronlO-

+ AGGUUAAGUUGUUCUUA 17

182 19068

CFTR-lntronlO-

+ UAUCAACAUGAAGGUUA 17

183 19069

CFTR-lntronlO-

- CUAAGUAUUAGAGGUUA 17

184 19070

CFTR-lntronlO-

+ CUAUUAUUCAACAUUUA 17

185 19071

CFTR-lntronlO-

+ UCU UUACGAGCACUUUA 17

186 19072

CFTR-lntronlO-

+ CAAGCCUGUAUUGUUUA 17

187 19073

CFTR-lntronlO-

+ CU U ACCG U AAU AG CAAC 17

188 19074

CFTR-lntronlO-

+ UCAUCACUUGCCUGAAC 17

189 19075

CFTR-lntronlO-

+ AACCUAUAAGGAAUAAC 17

190 19076

CFTR-lntronlO-

- CUUAUUCUUGUAAUAAC 17

191 19077

CFTR-lntronlO-

- UUUCUGGACUGAGUAAC 17

192 19078

CFTR-lntronlO-

+ UGAAACUCCCCACACAC 17

193 19079

618

5535.1 CFTR-lntronlO-

+ CGUAUUUCAGAAGACAC 17

194 19080

CFTR-lntronlO-

- CAU U U CAACU U AU ACAC 17

195 19081

CFTR-lntronlO-

- UUCUGUUUAAAUAGCAC 17

196 19082

CFTR-lntronlO-

- AUAGAAUUUUGCAUCAC 17

197 19083

CFTR-lntronlO-

- CUGGCAUAGAGUAAGAC 17

198 19084

CFTR-lntronlO-

+ UG U U CU U CAAACCAG AC 17

199 19085

CFTR-lntronlO-

- AGUGCCUAGCACUUGAC 17

200 19086

CFTR-lntronlO-

+ UACAACAGUCUUUAUAC 17

201 19087

CFTR-lntronlO-

- CAAAU U CCAAG ACU U AC 17

202 19088

CFTR-lntronlO-

- CU AAGAA CAACU UAACC 17

203 19089

CFTR-lntronlO-

+ CUACUUCCACUACUACC 17

204 19090

CFTR-lntronlO-

- CUAACACCUACCCUACC 17

205 19091

CFTR-lntronlO-

+ U UACUGUGAAUGGUGCC 17

206 19092

CFTR-lntronlO-

- ACCAAGGUAGCCAAUCC 17

207 19093

CFTR-lntronlO-

+ AAGAGACUCCUGAAUCC 17

208 19094

CFTR-lntronlO-

+ UAUAGCUCUGAUAAUCC 17

209 19095

CFTR-lntronlO-

- AAGACAGCUGGCUAUCC 17

210 19096

CFTR-lntronlO-

+ AUUAGCAAGUGGACUCC 17

211 19097

CFTR-lntronlO-

- UUCUUUUGAUAUACUCC 17

212 19098

CFTR-lntronlO-

- UGCCCUUGACUGAAAGC 17

213 19099

CFTR-lntronlO-

- UAAAUUUGGUGUCAGGC 17

214 19100

619

5535.1 CFTR-lntronlO-

- UAGUGUGAAGAUGGGGC 17

215 19101

CFTR-lntronlO-

+ UCAUGUUAGACAUAUGC 17

216 19102

CFTR-lntronlO-

+ CAAGACUUCACACCUGC 17

217 19103

CFTR-lntronlO-

- AGCAGACCCAAAUCUGC 17

218 19104

CFTR-lntronlO-

+ AUUUAUCUCGAAAUUGC 17

219 19105

CFTR-lntronlO-

+ U U AG U AG AAACCU AAU C 17

220 19106

CFTR-lntronlO-

- UUAGGGAAUGCAGACUC 17

221 19107

CFTR-lntronlO-

- AGCUGUGCAUUU UCCUC 17

222 19108

CFTR-lntronlO-

- ACUAAGGCUUAUUUCUC 17

223 19109

CFTR-lntronlO-

- UAACUUUUCUUAUUGUC 17

224 19110

CFTR-lntronlO-

- ACCAAAACU UUAUUGUC 17

225 19111

CFTR-lntronlO-

- CUGGCUAUCCAGGAUUC 17

226 19112

CFTR-lntronlO-

+ UGACAUCAGUUGGGUUC 17

227 19113

CFTR-lntronlO-

+ UCAAUUGUAUUAGCAAG 17

228 19114

CFTR-lntronlO-

- AGUAGGCUUCCUAUAAG 17

229 19115

CFTR-lntronlO-

+ U UAACCCAUCUAUUAAG 17

230 19116

CFTR-lntronlO-

+ UAUUGGACCAGACACAG 17

231 19117

CFTR-lntronlO-

- CUAGUUUCAAGGAAGAG 17

232 19118

CFTR-lntronlO-

+ UACCAAAUUGUAUUGAG 17

233 19119

CFTR-lntronlO-

+ ACACCAAAU U U AU UG AG 17

234 19120

CFTR-lntronlO-

+ AAAG U UG U CCAAG AU AG 17

235 19121

620

5535.1 CFTR-lntronlO-

+ U UUCCGUGCAUCACUAG 17

236 19122

CFTR-lntronlO-

- CUUGAUCCAGGUAGUAG 17

237 19123

CFTR-lntronlO-

- AUCGGCGGUGGAGGUAG 17

238 19124

CFTR-lntronlO-

- AAGAGAAAGGGGUGUAG 17

239 19125

CFTR-lntronlO-

- UCUCUGGGUGAGAUUAG 17

240 19126

CFTR-lntronlO-

+ AUCAACAUGAAGGUUAG 17

241 19127

CFTR-lntronlO-

- U G U G AG A A A A AG U U U AG 17

242 19128

CFTR-lntronlO-

- AAAUCAGUGCUUUUUCG 17

243 19129

CFTR-lntronlO-

+ CAAUAAUAGAGACAAGG 17

244 19130

CFTR-lntronlO-

- AGUAUUAGAGGUUAAGG 17

245 19131

CFTR-lntronlO-

- U U CAACU U AU ACACAGG 17

246 19132

CFTR-lntronlO-

- AUUAGAGGUUAAGGAGG 17

247 19133

CFTR-lntronlO-

- UACUAACUCAAUCUAGG 17

248 19134

CFTR-lntronlO-

- UCGGCGGUGGAGGUAGG 17

249 19135

CFTR-lntronlO-

- AGAGAAGUAAUCGGCGG 17

250 19136

CFTR-lntronlO-

- CAUAGAGUAAGACAGGG 17

251 19137

CFTR-lntronlO-

+ UUAAGUUGUUCUUAGGG 17

252 19138

CFTR-lntronlO-

- AGGAGCCAAAAAUUGGG 17

253 19139

CFTR-lntronlO-

- AGCCAAAAAUUGGGUGG 17

254 19140

CFTR-lntronlO-

- CUGGUAGUGUGAAGAUG 17

255 19141

CFTR-lntronlO-

- UAUCAAUAUCUAAGAUG 17

256 19142

621

5535.1 CFTR-lntronlO-

+ AUCUGUUAGUAAUGCUG 17

257 19143

CFTR-lntronlO-

- UUAAGGGCAUAGCUCUG 17

258 19144

CFTR-lntronlO-

+ AACUCAGUACCAUAGUG 17

259 19145

CFTR-lntronlO-

+ CUGU UAGUAAUGCUGUG 17

260 19146

CFTR-lntronlO-

- CAUCUCACCAGUGUGUG 17

261 19147

CFTR-lntronlO-

- CUCUCU UUUAACUAUUG 17

262 19148

CFTR-lntronlO-

+ UGAGUGGAAAUUUUUUG 17

263 19149

CFTR-lntronlO-

- U U U C AG G AG C C A A A A A U 17

264 19150

CFTR-lntronlO-

+ ACCAUUAUCUACACAAU 17

265 19151

CFTR-lntronlO-

- AUGGGCUAAAGGGCAAU 17

266 19152

CFTR-lntronlO-

- CUU UCUAGUAUUAGAAU 17

267 19153

CFTR-lntronlO-

+ AUGGCAUGAGUACGAAU 17

268 19154

CFTR-lntronlO-

+ CCUAGAUGAUUAUUAAU 17

269 19155

CFTR-lntronlO-

- UUUUCCUCUUAAUAGAU 17

270 19156

CFTR-lntronlO-

+ AAAAAAGUUACCUGGAU 17

271 19157

CFTR-lntronlO-

+ UUAUCCAUUAAUCCUAU 17

272 19158

CFTR-lntronlO-

+ AAUGCUUGACCACUUAU 17

273 19159

CFTR-lntronlO-

- UCCCUGU UAUUCCUUAU 17

274 19160

CFTR-lntronlO-

+ ACAACAGUCUUUAUACU 17

275 19161

CFTR-lntronlO-

+ UUGCUUCACCUGCUACU 17

276 19162

CFTR-lntronlO-

+ AUCUUAUAGAGAUUACU 17

277 19163

622

5535.1 CFTR-lntronlO-

+ UUUUGAGCCUAUCACCU 17

278 19164

CFTR-lntronlO-

+ ACCUGGAUUGGCUACCU 17

279 19165

CFTR-lntronlO-

+ CACU UGUUGACAGUCCU 17

280 19166

CFTR-lntronlO-

+ ACU CAG U CC AG AAAG C U 17

281 19167

CFTR-lntronlO-

+ ACUCAUAAGGGACCGCU 17

282 19168

CFTR-lntronlO-

- AAAUUUGGUGUCAGGCU 17

283 19169

CFTR-lntronlO-

+ AGCCUAUCACCUAGGCU 17

284 19170

CFTR-lntronlO-

+ UAUACCUGUCAAGUGCU 17

285 19171

CFTR-lntronlO-

- CCUAU UAAUAAUCAUCU 17

286 19172

CFTR-lntronlO-

- UAGGGAAUGCAGACUCU 17

287 19173

CFTR-lntronlO-

+ UAGAGAGAAACAUCUCU 17

288 19174

CFTR-lntronlO-

- CUAAGGCUUAUUUCUCU 17

289 19175

CFTR-lntronlO-

+ UAAUUGCCAGUAAGUCU 17

290 19176

CFTR-lntronlO-

+ AUUUUCUCGGUAUUUCU 17

291 19177

CFTR-lntronlO-

- AUUUUUGACUAUACAGU 17

292 19178

CFTR-lntronlO-

+ U UCUGCU UGACAUCAGU 17

293 19179

CFTR-lntronlO-

+ ACCAAAUUGUAUUGAGU 17

294 19180

CFTR-lntronlO-

+ AAGUUGUCCAAGAUAGU 17

295 19181

CFTR-lntronlO-

- CAAAU AG AG AUG U U AG U 17

296 19182

CFTR-lntronlO-

+ UGUGAAUGGUGCCAGGU 17

297 19183

CFTR-lntronlO-

- UAAUCGGCGGUGGAGGU 17

298 19184

623

5535.1 CFTR-lntronlO-

- UGAUGGUAUUGCAGGGU 17

299 19185

CFTR-lntronlO-

+ AUGGUGCCAGGUAGGGU 17

300 19186

CFTR-lntronlO-

+ UAAGUUGUUCUUAGGGU 17

301 19187

CFTR-lntronlO-

- UUGACUAUACAGUGGGU 17

302 19188

CFTR-lntronlO-

+ AAAGCUGUUUCGUAUGU 17

303 19189

CFTR-lntronlO-

+ UCUGUUAGUAAUGCUGU 17

304 19190

CFTR-lntronlO-

- AGCAGUGCUGCUGCUGU 17

305 19191

CFTR-lntronlO-

- UU UUUAGGCUAU UCUGU 17

306 19192

CFTR-lntronlO-

- U U C AG G AG C C A A A A A U U 17

307 19193

CFTR-lntronlO-

- ACCCACU CAAU ACAAU U 17

308 19194

CFTR-lntronlO-

- AUGCUAAUAAUACAAUU 17

309 19195

CFTR-lntronlO-

- AAUAUCACCAACUCAU U 17

310 19196

CFTR-lntronlO-

+ AUCUCUGCAAACAUAU U 17

311 19197

CFTR-lntronlO-

- ACUUAACCUGGCAUAUU 17

312 19198

CFTR-lntronlO-

+ CAACUAACAUCUCUAUU 17

313 19199

CFTR-lntronlO-

- UGCCUU UUAGUAGUAU U 17

314 19200

CFTR-lntronlO-

+ CAAUGGUUGUCUGUAU U 17

315 19201

CFTR-lntronlO-

+ AUACUUAGAAUGCCCUU 17

316 19202

CFTR-lntronlO-

- UUGCAGGGUGGGGCCU U 17

317 19203

CFTR-lntronlO-

- AUGUGCAAAAAUAGCUU 17

318 19204

CFTR-lntronlO-

+ CAGGUUAAGUUGUUCU U 17

319 19205

624

5535.1 CFTR-lntronlO-

- U U AG U U AGCAU AAAG U U 17

320 19206

CFTR-lntronlO-

+ UCUGCUUGACAUCAGUU 17

321 19207

CFTR-lntronlO-

+ U U AU CAACAUG AAGG U U 17

322 19208

CFTR-lntronlO-

- AGUGCUUUUUCGAGGU U 17

323 19209

CFTR-lntronlO-

- UUGGAUGGAGCUUGGUU 17

324 19210

CFTR-lntronlO-

+ UUCAUGGAAAGCUUGU U 17

325 19211

CFTR-lntronlO-

- UUGUGUACUUGUGAUU U 17

326 19212

CFTR-lntronlO-

- UAUGCACUCUUUGCU UU 17

327 19213

CFTR-lntronlO-

+ UCCUGACAAUAAAGUUU 17

328 19214

CFTR-lntronlO-

- UGGAUGGAGCUUGGUUU 17

329 19215

CFTR-lntronlO-

- AGAGCUAUAUUGUGUU U 17

330 19216

CFTR-lntronlO-

+ CUCCCCCACCCAAUUUU 17

331 19217

CFTR-lntronlO-

+ CAGAGCUAUGCCCUUAAAAA 20

332 19218

CFTR-lntronlO-

- UGCU UCAGAAGUCUAUAAAA 20

333 19219

CFTR-lntronlO-

- AUAAUCAUCUAGGCUGCAAA 20

334 19220

CFTR-lntronlO-

+ C AG C U A A A A U G AC A A U C A A A 20

335 19221

CFTR-lntronlO-

- CGUGUUAUUCAGCCAAUAAA 20

336 19222

CFTR-lntronlO-

- CUAACCUUCAUGUUGAUAAA 20

337 19223

CFTR-lntronlO-

+ CCAUUCCUAAUACUACUAAA 20

338 19224

CFTR-lntronlO-

- UAGUAUUAGAAUGGGCUAAA 20

339 19225

CFTR-lntronlO-

+ CCCAUUAUCUUUCUAGUAAA 20

340 19226

625

5535.1 CFTR-lntronlO-

- UUAAUGGAUAAGUUGAACAA 20

341 19227

CFTR-lntronlO-

+ U UUUACCAUUAUCUACACAA 20

342 19228

CFTR-lntronlO-

- CUAGGUUUAAUUUUGUACAA 20

343 19229

CFTR-lntronlO-

+ AAGUGUUUAAAUAUUCCCAA 20

344 19230

CFTR-lntronlO-

+ U C A A A AG A A U A AG G C A U C A A 20

345 19231

CFTR-lntronlO-

+ AUAAGCCAGCUUUCAGUCAA 20

346 19232

CFTR-lntronlO-

- CCAACUGAUGUCAAGCAGAA 20

347 19233

CFTR-lntronlO-

- AGAGCUUUCUAGUAU UAGAA 20

348 19234

CFTR-lntronlO-

+ CUAAAACUGAGUAGAAGGAA 20

349 19235

CFTR-lntronlO-

- CCUUUUAGUAGUAUUAGGAA 20

350 19236

CFTR-lntronlO-

- AAUUAAGAAAGACUCCUGAA 20

351 19237

CFTR-lntronlO-

- AGUGGCCUUUAAACAUUGAA 20

352 19238

CFTR-lntronlO-

- AAUG U AG U AU U AAACCAU AA 20

353 19239

CFTR-lntronlO-

+ CUAAAGCAAAGAGUGCAUAA 20

354 19240

CFTR-lntronlO-

- AUAACCCAUUGUGUAGAUAA 20

355 19241

CFTR-lntronlO-

- CCUAACCU UCAUGUUGAUAA 20

356 19242

CFTR-lntronlO-

- AUUUUGGUGUAGUUCUAUAA 20

357 19243

CFTR-lntronlO-

- UU UGACCUAAGAUAUCCUAA 20

358 19244

CFTR-lntronlO-

- CUAGUAUUAGAAUGGGCUAA 20

359 19245

CFTR-lntronlO-

+ UUGGGUAACAAUAAUAUUAA 20

360 19246

CFTR-lntronlO-

+ AAUUCAACUUUAUCUGUUAA 20

361 19247

626

5535.1 CFTR-lntronlO-

- AGUUAGCAAUGGUCUAAACA 20

362 19248

CFTR-lntronlO-

+ AUGACAAUCAAAUGGGAACA 20

363 19249

CFTR-lntronlO-

+ AGAACCUAUAAGGAAUAACA 20

364 19250

CFTR-lntronlO-

- AG U U U U AAACAG AAG U AACA 20

365 19251

CFTR-lntronlO-

- UGCAUUCCCUCAUCCAACCA 20

366 19252

CFTR-lntronlO-

+ UACUAAAGACUUCACCCUCA 20

367 19253

CFTR-lntronlO-

+ CAUAAGCCAGCUUUCAGUCA 20

368 19254

CFTR-lntronlO-

+ UAAAUCUAAAAGCUAAUUCA 20

369 19255

CFTR-lntronlO-

+ ACGAAUUGG UACAAAU U U CA 20

370 19256

CFTR-lntronlO-

- AUAAGAUUCU A AAG G A A AG A 20

371 19257

CFTR-lntronlO-

- AAGUCUAGUUUCAAGGAAGA 20

372 19258

CFTR-lntronlO-

- CCCAACUGAUGUCAAGCAGA 20

373 19259

CFTR-lntronlO-

+ ACUGACUAAAACUGAGUAGA 20

374 19260

CFTR-lntronlO-

+ UGGCUACCUUGGUUGGAUGA 20

375 19261

CFTR-lntronlO-

- CC AG U U CAG G CAAG U G A U G A 20

376 19262

CFTR-lntronlO-

- CUUAUGAAAAGCAGCUAUGA 20

377 19263

CFTR-lntronlO-

- UUGUUAAAGAAUGACUGUGA 20

378 19264

CFTR-lntronlO-

+ AGGGUCUCUCUAAGGUGUGA 20

379 19265

CFTR-lntronlO-

- AACCGGUGUCUUCUGAAAUA 20

380 19266

CFTR-lntronlO-

+ AGGAGUAUAU C A A A AG A A U A 20

381 19267

CFTR-lntronlO-

+ AGUCCUCUGUGCUU UGAAUA 20

382 19268

627

5535.1 CFTR-lntronlO-

- CCCAUAAAUGUUGAAUAAUA 20

383 19269

CFTR-lntronlO-

+ AGCCUAGAUGAUUAUUAAUA 20

384 19270

CFTR-lntronlO-

- UAUUGAUCAUUGCCUCACUA 20

385 19271

CFTR-lntronlO-

- UAAAGUGCUCGUAAAGACUA 20

386 19272

CFTR-lntronlO-

- CUUUGACCUAAGAUAUCCUA 20

387 19273

CFTR-lntronlO-

+ UGAGCCUAUCACCUAGGCUA 20

388 19274

CFTR-lntronlO-

- AGUAAUCGGCGGUGGAGGUA 20

389 19275

CFTR-lntronlO-

- UGUUUUUAGGCUAUUCUGUA 20

390 19276

CFTR-lntronlO-

+ AGCACUCUAUUUAGAGUGUA 20

391 19277

CFTR-lntronlO-

- UAAGAAGAGAAAGGGGUGUA 20

392 19278

CFTR-lntronlO-

+ CAAUUAGUUUUAUGCCAUUA 20

393 19279

CFTR-lntronlO-

- UUGCAGGAGGUGAGGGAUUA 20

394 19280

CFTR-lntronlO-

- CUUGACUGAAAGCUGGCUUA 20

395 19281

CFTR-lntronlO-

+ CUU UAUCAACAUGAAGGUUA 20

396 19282

CFTR-lntronlO-

- AUUCUAAGUAUUAGAGGUUA 20

397 19283

CFTR-lntronlO-

+ CCCCUAUUAUUCAACAUUUA 20

398 19284

CFTR-lntronlO-

+ UAGUCUUUACGAGCACUUUA 20

399 19285

CFTR-lntronlO-

- AGAAAGAUAAUGGGAGAAAC 20

400 19286

CFTR-lntronlO-

+ UACGAUAUAAGAAAUGAAAC 20

401 19287

CFTR-lntronlO-

+ UUCGUAUGUAGGAAAACAAC 20

402 19288

CFTR-lntronlO-

+ CAGAACCUAUAAGGAAUAAC 20

403 19289

628

5535.1 CFTR-lntronlO-

- UAGCUUAUUCUUGUAAUAAC 20

404 19290

CFTR-lntronlO-

- AUGAAACUGUUAUAAUUAAC 20

405 19291

CFTR-lntronlO-

+ CUCCGUAUUUCAGAAGACAC 20

406 19292

CFTR-lntronlO-

- UAUCAUUUCAACU UAUACAC 20

407 19293

CFTR-lntronlO-

+ UUAGUAUUAAGUAUAGCCAC 20

408 19294

CFTR-lntronlO-

- UGGGUGAGAUUAGAGGCCAC 20

409 19295

CFTR-lntronlO-

- UGAUUCUGUU UAAAUAGCAC 20

410 19296

CFTR-lntronlO-

- AGUAUAGAAUUUUGCAUCAC 20

411 19297

CFTR-lntronlO-

- AGGCUGGCAUAGAGUAAGAC 20

412 19298

CFTR-lntronlO-

+ UACUGUUCU UCAAACCAGAC 20

413 19299

CFTR-lntronlO-

+ UGUUACAACAGUCUUUAUAC 20

414 19300

CFTR-lntronlO-

- AUUGAUGAGCAGAUAAUUAC 20

415 19301

CFTR-lntronlO-

- UUACAAAU UCCAAGACU U AC 20

416 19302

CFTR-lntronlO-

+ UACAAAUAUUGACUAUUUAC 20

417 19303

CFTR-lntronlO-

- ACCCUAAGAACAACUUAACC 20

418 19304

CFTR-lntronlO-

+ AUACUACUUCCACUACUACC 20

419 19305

CFTR-lntronlO-

- ACACUAACACCUACCCUACC 20

420 19306

CFTR-lntronlO-

+ AG AU ACU AAAAAAAG U U ACC 20

421 19307

CFTR-lntronlO-

+ UCU UUACUGUGAAUGGUGCC 20

422 19308

CFTR-lntronlO-

- CCAACCAAGGUAGCCAAUCC 20

423 19309

CFTR-lntronlO-

+ CAAUAUAGCUCUGAUAAUCC 20

424 19310

629

5535.1 CFTR-lntronlO-

- AGUGAAUGAAUGUGGUAUCC 20

425 19311

CFTR-lntronlO-

+ UGUAUUAGCAAGUGGACUCC 20

426 19312

CFTR-lntronlO-

+ CUUGACAUCAGU UGGGUUCC 20

427 19313

CFTR-lntronlO-

- AGUAAGGAGGUCACUGAGGC 20

428 19314

CFTR-lntronlO-

- AGUUUCAAGGAAGAGGGGGC 20

429 19315

CFTR-lntronlO-

- UGGUAGUGUGAAGAUGGGGC 20

430 19316

CFTR-lntronlO-

+ U UGGUUGGAUGAGGGAAUGC 20

431 19317

CFTR-lntronlO-

+ UUUUCAUGUUAGACAUAUGC 20

432 19318

CFTR-lntronlO-

+ AGUGCUAUUUAAACAGAAUC 20

433 19319

CFTR-lntronlO-

- AAAAGCUGUGCAUUUUCCUC 20

434 19320

CFTR-lntronlO-

- AAGACUAAGGCUUAUUUCUC 20

435 19321

CFTR-lntronlO-

- UGGGACUGACUAUACCUGUC 20

436 19322

CFTR-lntronlO-

+ AAUAGAGACAAGGUGGUGUC 20

437 19323

CFTR-lntronlO-

- CACUCAAUAAAUUUGGUGUC 20

438 19324

CFTR-lntronlO-

- UUCUAACUUU UCUUAU UGUC 20

439 19325

CFTR-lntronlO-

- AGGACCAAAACUUUAUUGUC 20

440 19326

CFTR-lntronlO-

- CAGCUGGCUAUCCAGGAUUC 20

441 19327

CFTR-lntronlO-

+ UAUUAAGAGGAAAAGACUUC 20

442 19328

CFTR-lntronlO-

+ UACGAAUUGGUACAAAUUUC 20

443 19329

CFTR-lntronlO-

- CUUACUGGCAAUUAAAUUUC 20

444 19330

CFTR-lntronlO-

+ UUGAUAAAUAAUUGCCUUUC 20

445 19331

630

5535.1 CFTR-lntronlO-

+ CCUAAAAACAUUAGCCAAAG 20

446 19332

CFTR-lntronlO-

+ UAGGAUAUCUUAGGUCAAAG 20

447 19333

CFTR-lntronlO-

+ UAGGGUGGGAUAUGGAGAAG 20

448 19334

CFTR-lntronlO-

- CAAGUCUAGUUUCAAGGAAG 20

449 19335

CFTR-lntronlO-

- UUUCCAUAUUCAAAGCACAG 20

450 19336

CFTR-lntronlO-

+ ACAGCUAAAGUAUUACCCAG 20

451 19337

CFTR-lntronlO-

- AGUCUAUAUUUGUUUUCCAG 20

452 19338

CFTR-lntronlO-

+ UGCUAUUUAAACAGAAUCAG 20

453 19339

CFTR-lntronlO-

+ AUAUUGUUACAUAAAAAGAG 20

454 19340

CFTR-lntronlO-

- AG U CU AG U U U CAAGG AAG AG 20

455 19341

CFTR-lntronlO-

+ AAUUACCAAAUUGUAUUGAG 20

456 19342

CFTR-lntronlO-

+ CUGACACCAAAUUUAU UGAG 20

457 19343

CFTR-lntronlO-

- CCAUAAAUGUUGAAUAAUAG 20

458 19344

CFTR-lntronlO-

+ UGGAAAGUUGUCCAAGAUAG 20

459 19345

CFTR-lntronlO-

+ ACUUUUCCGUGCAUCACUAG 20

460 19346

CFTR-lntronlO-

- UGGCUUGAUCCAGGUAGUAG 20

461 19347

CFTR-lntronlO-

- AUUUCUCUGGGUGAGAUUAG 20

462 19348

CFTR-lntronlO-

- AAGGGCAUUCUAAGUAUUAG 20

463 19349

CFTR-lntronlO-

- AGCUAUGAAGGCAGAGUUAG 20

464 19350

CFTR-lntronlO-

+ U UUAUCAACAUGAAGGUUAG 20

465 19351

CFTR-lntronlO-

- AUAAAAUCAGUGCUUUUUCG 20

466 19352

631

5535.1 CFTR-lntronlO-

- CUAAGUAUUAGAGGUUAAGG 20

467 19353

CFTR-lntronlO-

- CAU U U CAACU U AU ACACAGG 20

468 19354

CFTR-lntronlO-

+ U UGUUACAUAAAAAGAGAGG 20

469 19355

CFTR-lntronlO-

- AGUAUUAGAGGUUAAGGAGG 20

470 19356

CFTR-lntronlO-

- UAAUCGGCGGUGGAGGUAGG 20

471 19357

CFTR-lntronlO-

- ACUGUCAGAGAAGUAAUCGG 20

472 19358

CFTR-lntronlO-

- AUUCUGUAGGGAGACAAGGG 20

473 19359

CFTR-lntronlO-

- UGGCAUAGAGUAAGACAGGG 20

474 19360

CFTR-lntronlO-

+ AGGUUAAGUUGUUCUUAGGG 20

475 19361

CFTR-lntronlO-

- UUCAGGAGCCAAAAAUUGGG 20

476 19362

CFTR-lntronlO-

- AGAGAAGUAAUCGGCGGUGG 20

477 19363

CFTR-lntronlO-

- AGGAGCCAAAAAUUGGGUGG 20

478 19364

CFTR-lntronlO-

- ACAAAGCUAGUGAAUGAAUG 20

479 19365

CFTR-lntronlO-

- AUUUAUCAAUAUCUAAGAUG 20

480 19366

CFTR-lntronlO-

+ U UGGCUACCUUGGUUGGAUG 20

481 19367

CFTR-lntronlO-

+ CCUAUUAUUCAACAUUUAUG 20

482 19368

CFTR-lntronlO-

+ CACGAAUAUAUUCUU UUAUG 20

483 19369

CFTR-lntronlO-

- UUUGAUUGUCAUUUUAGCUG 20

484 19370

CFTR-lntronlO-

+ AUCAUCUGUUAGUAAUGCUG 20

485 19371

CFTR-lntronlO-

- UUUUUAAGGGCAUAGCUCUG 20

486 19372

CFTR-lntronlO-

+ AAGGAAAUGGGGUAUAAGUG 20

487 19373

632

5535.1 CFTR-lntronlO-

+ UAAAACUCAGUACCAUAGUG 20

488 19374

CFTR-lntronlO-

- CAGGAGCCAAAAAUUGGGUG 20

489 19375

CFTR-lntronlO-

+ CAUCUGUUAGUAAUGCUGUG 20

490 19376

CFTR-lntronlO-

- UAUGGCAUCUCACCAGUGUG 20

491 19377

CFTR-lntronlO-

- UGGCAUCUCACCAGUGUGUG 20

492 19378

CFTR-lntronlO-

- UACGGUAAGCUCAAGCAUUG 20

493 19379

CFTR-lntronlO-

- UUGGUAUUUACCAUAUAUUG 20

494 19380

CFTR-lntronlO-

- UUGCUCUCUUUUAACUAUUG 20

495 19381

CFTR-lntronlO-

+ UAUUGAGUGGAAAUUU UUUG 20

496 19382

CFTR-lntronlO-

- UGCUUUCAGGAG CCA A A A A U 20

497 19383

CFTR-lntronlO-

+ AG C U A A A A U G AC A A U C A A A U 20

498 19384

CFTR-lntronlO-

- AGAAUGGGCUAAAGGGCAAU 20

499 19385

CFTR-lntronlO-

+ UGUAUGGCAUGAGUACGAAU 20

500 19386

CFTR-lntronlO-

- CCG U U U ACU AG AAAG AU AAU 20

501 19387

CFTR-lntronlO-

- AAUACUGU CAG AG AAG U AAU 20

502 19388

CFTR-lntronlO-

+ CAGCCUAGAUGAUUAU UAAU 20

503 19389

CFTR-lntronlO-

- C A AG U G C A A AG CUUUCAGAU 20

504 19390

CFTR-lntronlO-

+ CUAAAAAAAGUUACCUGGAU 20

505 19391

CFTR-lntronlO-

+ UCU UUGUGUUAACAAAAUAU 20

506 19392

CFTR-lntronlO-

+ AACUUAUCCAUUAAUCCUAU 20

507 19393

CFTR-lntronlO-

+ ACAAAUGCUUGACCACU UAU 20

508 19394

633

5535.1 CFTR-lntronlO-

+ CCCUAU UAUUCAACAUU UAU 20

509 19395

CFTR-lntronlO-

+ U U CU U U AACAAACCU U U U AU 20

510 19396

CFTR-lntronlO-

- AGCUUAUUCUUGUAAUAACU 20

511 19397

CFTR-lntronlO-

+ CACUUGCU UCACCUGCUACU 20

512 19398

CFTR-lntronlO-

+ AAAAUCUUAUAGAGAUUACU 20

513 19399

CFTR-lntronlO-

+ UUUUUUUGAGCCUAUCACCU 20

514 19400

CFTR-lntronlO-

- AGAGGAAGGCAGUGGUCCCU 20

515 19401

CFTR-lntronlO-

+ AGGCACUUGUUGACAGUCCU 20

516 19402

CFTR-lntronlO-

- AACAGGUUUUGGAUGGAGCU 20

517 19403

CFTR-lntronlO-

+ AAAACUCAUAAGGGACCGCU 20

518 19404

CFTR-lntronlO-

- AAUAAAUUUGGUGUCAGGCU 20

519 19405

CFTR-lntronlO-

+ U UGAGCCUAUCACCUAGGCU 20

520 19406

CFTR-lntronlO-

- UUCAAAUUAUUUCUACUGCU 20

521 19407

CFTR-lntronlO-

+ UAAUAUACCUGUCAAGUGCU 20

522 19408

CFTR-lntronlO-

- UCCCCUAUUAAUAAUCAUCU 20

523 19409

CFTR-lntronlO-

- UCUUGCU UUUCCCACUAUCU 20

524 19410

CFTR-lntronlO-

- AGACUAAGGCUUAUUUCUCU 20

525 19411

CFTR-lntronlO-

+ AUUUAAUUGCCAGUAAGUCU 20

526 19412

CFTR-lntronlO-

+ AAUAAUUUGAACAACAUUCU 20

527 19413

CFTR-lntronlO-

- UAUGUGAAAAUAUCACUUCU 20

528 19414

CFTR-lntronlO-

+ CCCUUCUGCU UGACAUCAGU 20

529 19415

634

5535.1 CFTR-lntronlO-

+ AGUCAGUUUUAUUU UUCAGU 20

530 19416

CFTR-lntronlO-

+ UGUACAUUUUCCUAAUGAGU 20

531 19417

CFTR-lntronlO-

+ AUUACCAAAUUGUAUUGAGU 20

532 19418

CFTR-lntronlO-

- AGUAGUGGAAGUAGUAUAGU 20

533 19419

CFTR-lntronlO-

+ UACUGUGAAUGGUGCCAGGU 20

534 19420

CFTR-lntronlO-

+ UGUUACAUAAAAAGAGAGGU 20

535 19421

CFTR-lntronlO-

- AAGUAAUCGGCGGUGGAGGU 20

536 19422

CFTR-lntronlO-

- UCAGGAGCCAAAAAUUGGGU 20

537 19423

CFTR-lntronlO-

+ CCUGGAUUGGCUACCUUGGU 20

538 19424

CFTR-lntronlO-

+ U UAAAAGCUGUUUCGUAUGU 20

539 19425

CFTR-lntronlO-

+ UCAUCUGUUAGUAAUGCUGU 20

540 19426

CFTR-lntronlO-

- AUGUUUUUAGGCUAUUCUGU 20

541 19427

CFTR-lntronlO-

- AUGGCAUCUCACCAGUGUGU 20

542 19428

CFTR-lntronlO-

- CUUACCCACUCAAUACAAUU 20

543 19429

CFTR-lntronlO-

- AAAAAUAUCACCAACUCAUU 20

544 19430

CFTR-lntronlO-

+ AAGAUCUCUGCAAACAUAUU 20

545 19431

CFTR-lntronlO-

- ACAACUUAACCUGGCAUAUU 20

546 19432

CFTR-lntronlO-

+ AUCCAACUAACAUCUCUAUU 20

547 19433

CFTR-lntronlO-

+ CAUCAAUGGUUGUCUGUAUU 20

548 19434

CFTR-lntronlO-

- CAGAAGUAACAGGGCCACUU 20

549 19435

CFTR-lntronlO-

- AUAGAUUAGCUUAUAUACUU 20

550 19436

635

5535.1 CFTR-lntronlO-

+ CUAAUACUUAGAAUGCCCUU 20

551 19437

CFTR-lntronlO-

- UAGAUGUGCAAAAAUAGCUU 20

552 19438

CFTR-lntronlO-

+ UGCCAGGUUAAGUUGUUCUU 20

553 19439

CFTR-lntronlO-

+ CCUUCUGCUUGACAUCAGUU 20

554 19440

CFTR-lntronlO-

+ CCUUUAUCAACAUGAAGGUU 20

555 19441

CFTR-lntronlO-

- AUCAGUGCUUUUUCGAGGUU 20

556 19442

CFTR-lntronlO-

+ UAAUUCAUGGAAAGCUUGUU 20

557 19443

CFTR-lntronlO-

- CAUUUGUGUACUUGUGAUUU 20

558 19444

CFTR-lntronlO-

+ AGAUCUCUGCAAACAUAUUU 20

559 19445

CFTR-lntronlO-

- CUUUAUGCACUCUUUGCUUU 20

560 19446

CFTR-lntronlO-

+ UUCUCCUGACAAUAAAGUUU 20

561 19447

CFTR-lntronlO-

- AUAAUGGGAGAAACAGGUUU 20

562 19448

CFTR-lntronlO-

- UUUUGGAUGGAGCUUGGUUU 20

563 19449

CFTR-lntronlO-

- AUCAGAGCUAUAUUGUGUUU 20

564 19450

CFTR-lntronlO-

- CCACUUUGGCUAAUGUUUUU 20

565 19451

Table 40C provides exemplary targeting domains for correcting a mutation (e.g., 3272- 26->G) in the CFTR gene selected according to the third tier parameters. The targeting domains bind within intron 10 and start with a 5'G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 40C

636

5535.1 Length

CFTR-lntronlO-

+ GACCAUCCCGGCUAAAA 17

566 19452

CFTR-lntronlO-

- G U UG AU AAG AAG AG AAA 17

567 19453

CFTR-lntronlO-

- GAUGUUUAUUUAUGAAA 17

568 19454

CFTR-lntronlO-

- GUUAUUCAGCCAAUAAA 17

569 19455

CFTR-lntronlO-

- GGUUUAAUUUUGUACAA 17

570 19456

CFTR-lntronlO-

+ GACUAAUCACCUCCCAA 17

571 19457

CFTR-lntronlO-

+ GUUCUCACAUGGCAGAA 17

572 19458

CFTR-lntronlO-

- GGUUGAUAAGAAGAGAA 17

573 19459

CFTR-lntronlO-

+ GAGGGAAUGCAGGAGAA 17

574 19460

CFTR-lntronlO-

+ GGGAGGCUGAAGCGGAA 17

575 19461

CFTR-lntronlO-

+ GGAUUUCAACAUAUGAA 17

576 19462

CFTR-lntronlO-

+ GGUAACAAUAAUAUUAA 17

577 19463

CFTR-lntronlO-

- GACCAGCGUGGGCAACA 17

578 19464

CFTR-lntronlO-

+ GUACAGUGGUGCAAUCA 17

579 19465

CFTR-lntronlO-

- GAAGGAAGGAAGUAAGA 17

580 19466

CFTR-lntronlO-

- G A A AG C A A UAGUAGAGA 17

581 19467

CFTR-lntronlO-

- GUAGGAGGAAGGAAGGA 17

582 19468

CFTR-lntronlO-

- GGAAGUAGGAGGAAGGA 17

583 19469

CFTR-lntronlO-

- GAAAAAGAAAGAGAGGA 17

584 19470

CFTR-lntronlO-

- GAAAGGAAGUAGGAGGA 17

585 19471

CFTR-lntronlO-

+ GUCCCAGCUACUUGGGA 17

586 19472

637

5535.1 CFTR-lntronlO-

- GUAUUCUAUCAUAUGGA 17

587 19473

CFTR-lntronlO-

- G AG AAACAGG U U U UGG A 17

588 19474

CFTR-lntronlO-

- GU UCAGGCAAGUGAUGA 17

589 19475

CFTR-lntronlO-

+ GGGUGAGGGUCUCUCUA 17

590 19476

CFTR-lntronlO-

+ GUGAAUGGUGCCAGGUA 17

591 19477

CFTR-lntronlO-

- GAAGAGAAAGGGGUGUA 17

592 19478

CFTR-lntronlO-

+ G AAAAAAAAU U CAAAAC 17

593 19479

CFTR-lntronlO-

+ GAUAUAAGAAAUGAAAC 17

594 19480

CFTR-lntronlO-

- GUAUUUUUAGUAGAGAC 17

595 19481

CFTR-lntronlO-

+ GGAGAAUGGCGUGAACC 17

596 19482

CFTR-lntronlO-

+ GAGAAUGGCGUGAACCC 17

597 19483

CFTR-lntronlO-

+ GUCUCACUCUGUCACCC 17

598 19484

CFTR-lntronlO-

- GUCUUACUCUGUCACCC 17

599 19485

CFTR-lntronlO-

+ GAGAAUUGCUUGAGCCC 17

600 19486

CFTR-lntronlO-

- GUCUCGCUCUGUCGCCC 17

601 19487

CFTR-lntronlO-

+ GCCACUGCACUCCAGCC 17

602 19488

CFTR-lntronlO-

+ GGAGAAUUGCUUGAGCC 17

603 19489

CFTR-lntronlO-

- GCCACUGCACUCUAGCC 17

604 19490

CFTR-lntronlO-

+ GUUUCACUGUGUUAGCC 17

605 19491

CFTR-lntronlO-

- GUUUCACCGUUUUAGCC 17

606 19492

CFTR-lntronlO-

- GCGCCCGCCACUACGCC 17

607 19493

638

5535.1 CFTR-lntronlO-

- GCGUGAGCCACCGCGCC 17

608 19494

CFTR-lntronlO-

- GU UUCACCAUGUUGGCC 17

609 19495

CFTR-lntronlO-

- GGAGAUCAAGACCAUCC 17

610 19496

CFTR-lntronlO-

+ GGAGAUCGAGACCAUCC 17

611 19497

CFTR-lntronlO-

- GUGAAUUGCUUGAGUCC 17

612 19498

CFTR-lntronlO-

- GGU UUCACCGUUUUAGC 17

613 19499

CFTR-lntronlO-

- GGCUGGAGUGCAGUGGC 17

614 19500

CFTR-lntronlO-

+ GCACCCGCCAUCACGUC 17

615 19501

CFTR-lntronlO-

+ GGGCGGAUCACGAGGUC 17

616 19502

CFTR-lntronlO-

- GCAUGAGCCACUGUGUC 17

617 19503

CFTR-lntronlO-

+ GGUGGGAUAUGGAGAAG 17

618 19504

CFTR-lntronlO-

+ G U A A U AG C A AC AG G A AG 17

619 19505

CFTR-lntronlO-

- GAUUUUUGACUAUACAG 17

620 19506

CFTR-lntronlO-

- GAGUUAGAGGAAGGCAG 17

621 19507

CFTR-lntronlO-

+ GU UUGUGUUUUUUGUAG 17

622 19508

CFTR-lntronlO-

+ GAGGCGGGCGGAUCACG 17

623 19509

CFTR-lntronlO-

- GAGUCAAAAAUUAUACG 17

624 19510

CFTR-lntronlO-

- GGAGUUUGAGACCAGCG 17

625 19511

CFTR-lntronlO-

- GAACAAAGACUUGCAGG 17

626 19512

CFTR-lntronlO-

+ GGCGUGAACCCGGGAGG 17

627 19513

CFTR-lntronlO-

- G G A AG A A AG G A AG U AG G 17

628 19514

639

5535.1 CFTR-lntronlO-

- GUGAUGGUAUUGCAGGG 17

629 19515

CFTR-lntronlO-

- GAAGAAAGAAGGAAAUG 17

630 19516

CFTR-lntronlO-

- GAGGUGAUUAGUCCAUG 17

631 19517

CFTR-lntronlO-

+ GAGGCAGGCAGAUCAUG 17

632 19518

CFTR-lntronlO-

+ GAAUAUAUUCUUUUAUG 17

633 19519

CFTR-lntronlO-

+ G U AG C A A A U G A U A A A A U 17

634 19520

CFTR-lntronlO-

- GU UUACUAACUCAAUCU 17

635 19521

CFTR-lntronlO-

+ GUGCAGUGGCGCGAUCU 17

636 19522

CFTR-lntronlO-

- GCACAGUGGUGCGAUCU 17

637 19523

CFTR-lntronlO-

- GUGCAGUGGCGGGAUCU 17

638 19524

CFTR-lntronlO-

- GCUGUGCAUUUUCCUCU 17

639 19525

CFTR-lntronlO-

- GAGUUUGAGACCAGCGU 17

640 19526

CFTR-lntronlO-

+ GUGUUUUUUGUAGAGGU 17

641 19527

CFTR-lntronlO-

- GUACUACUGUAAUAAUU 17

642 19528

CFTR-lntronlO-

- GCAGGAGGUGAGGGAUU 17

643 19529

CFTR-lntronlO-

- GUUAUCUCUGAAAUUU U 17

644 19530

CFTR-lntronlO-

+ GAAUGCAGGAGAAUGGAAAA 20

645 19531

CFTR-lntronlO-

+ GUGUUCUCACAUGGCAGAAA 20

646 19532

CFTR-lntronlO-

+ GCAUCACGUGGUGUUU UAAA 20

647 19533

CFTR-lntronlO-

+ GGGAGGCUGAGGCAGGAGAA 20

648 19534

CFTR-lntronlO-

+ GAUGAGGGAAUGCAGGAGAA 20

649 19535

640

5535.1 CFTR-lntronlO-

- GGGAGACAAGGGAGGAAGCA 20

650 19536

CFTR-lntronlO-

+ GGCUGGGAAGUCCAAGAUCA 20

651 19537

CFTR-lntronlO-

- GAAGUAGGAGGAAGGAAGGA 20

652 19538

CFTR-lntronlO-

- GAAGAAAGGAAGUAGGAGGA 20

653 19539

CFTR-lntronlO-

+ GUAGUCCCAGCUACUUGGGA 20

654 19540

CFTR-lntronlO-

- GGGAGGUGAUUAGUCCAUGA 20

655 19541

CFTR-lntronlO-

- GACUGUUUAUGUUAUCUGUA 20

656 19542

CFTR-lntronlO-

- GCCACUUCCUGUUGCUAUUA 20

657 19543

CFTR-lntronlO-

- GUGUGUAUAUGUGUGUAUUA 20

658 19544

CFTR-lntronlO-

+ GUUCAAGCCUGUAUUGUUUA 20

659 19545

CFTR-lntronlO-

+ GAGCUUACCGUAAUAGCAAC 20

660 19546

CFTR-lntronlO-

+ GCAGGAGAAUGGCGUGAACC 20

661 19547

CFTR-lntronlO-

- GCAUAUAUAUAUUUUUAACC 20

662 19548

CFTR-lntronlO-

- GACAGAGUCUUACUGUCACC 20

663 19549

CFTR-lntronlO-

- GGAGUCUCGCUCUGUCGCCC 20

664 19550

CFTR-lntronlO-

+ GCAGGAGAAUUGCUUGAGCC 20

665 19551

CFTR-lntronlO-

+ GGAGUUUCACUGUGUUAGCC 20

666 19552

CFTR-lntronlO-

- GGGGU UUCACCGUUUUAGCC 20

667 19553

CFTR-lntronlO-

- GGGGU UUCACCAUGUUGGCC 20

668 19554

CFTR-lntronlO-

+ GAUGUAUCUCCAAAUAUGCC 20

669 19555

CFTR-lntronlO-

- GGAUGCCCU UGACUGAAAGC 20

670 19556

641

5535.1 CFTR-lntronlO-

- GAACACAGCAGGAAGACAGC 20

671 19557

CFTR-lntronlO-

- GCCUCACCCUCCCAAGUAGC 20

672 19558

CFTR-lntronlO-

- GCCUCAGCCUCCCAAGUAGC 20

673 19559

CFTR-lntronlO-

- GGAAGAGUCUUCCAAGUAGC 20

674 19560

CFTR-lntronlO-

+ GCCUCAGCCUCCCGAGUAGC 20

675 19561

CFTR-lntronlO-

+ GUUUGCCAUGUUGCCCACGC 20

676 19562

CFTR-lntronlO-

- GAGUCUUACUGUCACCAGGC 20

677 19563

CFTR-lntronlO-

- GCACUUUUGGAGGCAGAGGC 20

678 19564

CFTR-lntronlO-

+ GCACUUUGGGAGGCCGAGGC 20

679 19565

CFTR-lntronlO-

- GCUACUCGGGAGGCUGAGGC 20

680 19566

CFTR-lntronlO-

+ GCUACUUGGGAGGCUGAGGC 20

681 19567

CFTR-lntronlO-

+ GCUACUUGGGAGGGUGAGGC 20

682 19568

CFTR-lntronlO-

+ GAUUUCAACAUAUGAAUGGC 20

683 19569

CFTR-lntronlO-

+ GUGCAAGACUUCACACCUGC 20

684 19570

CFTR-lntronlO-

- GCUUCAGCCUCCCAAAGUGC 20

685 19571

CFTR-lntronlO-

- GCCUCGGCCUCCCAAAGUGC 20

686 19572

CFTR-lntronlO-

- GCCCGUAGUCCCAGCUACUC 20

687 19573

CFTR-lntronlO-

+ GGCGGGCGGAUCACGAGGUC 20

688 19574

CFTR-lntronlO-

+ GAAUUUAUUUCUCACAGUUC 20

689 19575

CFTR-lntronlO-

+ GUGUGUGUGUGUCCUUGUUC 20

690 19576

CFTR-lntronlO-

- GGGUUGAUAAGAAGAGAAAG 20

691 19577

642

5535.1 CFTR-lntronlO-

- GAUCACCUGAGCCUGAGAAG 20

692 19578

CFTR-lntronlO-

- G A A AG A AG G A AG G A AG U A AG 20

693 19579

CFTR-lntronlO-

- G U CACC AG G C U G G AG CACAG 20

694 19580

CFTR-lntronlO-

- GUGGAUUUUUGACUAUACAG 20

695 19581

CFTR-lntronlO-

- GCAGAGUUAGAGGAAGGCAG 20

696 19582

CFTR-lntronlO-

+ GCCGAGGCGGGCGGAUCACG 20

697 19583

CFTR-lntronlO-

- GUGGAGUCAAAAAUUAUACG 20

698 19584

CFTR-lntronlO-

+ GAAAUGAAACAGGCCGGGCG 20

699 19585

CFTR-lntronlO-

- GAGAAUGGCGUGAACCCAGG 20

700 19586

CFTR-lntronlO-

+ GU UUGUGUUUUUUGUAGAGG 20

701 19587

CFTR-lntronlO-

+ GAGAAUGGCGUGAACCCGGG 20

702 19588

CFTR-lntronlO-

+ GAGAAUUGCUUGAGCCCGGG 20

703 19589

CFTR-lntronlO-

- GUUCAGGCAAGUGAUGAUGG 20

704 19590

CFTR-lntronlO-

+ GCCGAGGCAGGCAGAUCAUG 20

705 19591

CFTR-lntronlO-

- GAACAG U AAGG AGG U CACUG 20

706 19592

CFTR-lntronlO-

- GGUGAUGGUAUUGCAGGGUG 20

707 19593

CFTR-lntronlO-

- G G C U C A A A A A A A A A A A A A A U 20

708 19594

CFTR-lntronlO-

- GCACCACUGUACCCUAGCCU 20

709 19595

CFTR-lntronlO-

- GCGCCACUGCACUCUAGCCU 20

710 19596

CFTR-lntronlO-

- GGAGCACAGUGGUGCGAUCU 20

711 19597

CFTR-lntronlO-

- GGAGUGCAGUGGCGGGAUCU 20

712 19598

643

5535.1 CFTR-lntronlO-

- GCUACUUGGGAGGCUGAGGU 20

713 19599

CFTR-lntronlO-

+ GGUUAAGUUGUUCUUAGGGU 20

714 19600

CFTR-lntronlO-

- GAGACGGGGUUUCACCAUGU 20

715 19601

CFTR-lntronlO-

- GCCUCGGCCUCCCAAAGUGU 20

716 19602

CFTR-lntronlO-

- GCAAUGCUAAUAAUACAAUU 20

717 19603

CFTR-lntronlO-

+ GAUCAAGGUGCCAGCAGAUU 20

718 19604

CFTR-lntronlO-

+ GUUUCCAAAUUUUUUUUAUU 20

719 19605

CFTR-lntronlO-

+ GCCUGUAGUCCCAGCUACUU 20

720 19606

CFTR-lntronlO-

- GUAUUGCAGGGUGGGGCCUU 20

721 19607

CFTR-lntronlO-

+ GCCUGUAAUCCCAACACUUU 20

722 19608

CFTR-lntronlO-

+ GCCUAUAAACCCAGCACUUU 20

723 19609

CFTR-lntronlO-

+ GCCUGUAAUCCCAGCACUUU 20

724 19610

CFTR-lntronlO-

- GAACACUUUAUAGUUUUUUU 20

725 19611

Table 40D provides exemplary targeting domains for correcting a mutation (e.g., 3272- 26->G) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within intron 10. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 40D

644

5535.1 CFTR-lntronlO-

+ UAUGAUUUUAUGAAAAA 17

727 19613

CFTR-lntronlO-

+ UGCAGGAGAAUGG A A A A 17

728 19614

CFTR-lntronlO-

+ UGCAUAAAGGUUGAAAA 17

729 19615

CFTR-lntronlO-

- UUCAGAAGUCUAU A A A A 17

730 19616

CFTR-lntronlO-

- A AAG AAAAAAC AG C AAA 17

731 19617

CFTR-lntronlO-

+ AG U AAAAAAAAAU CAAA 17

732 19618

CFTR-lntronlO-

+ CUAAAAUGACAAUCAAA 17

733 19619

CFTR-lntronlO-

+ A A A AG C U G A A AG U CAAA 17

734 19620

CFTR-lntronlO-

+ AUUCAAUGAAAAAGAAA 17

735 19621

CFTR-lntronlO-

+ U UCUCACAUGGCAGAAA 17

736 19622

CFTR-lntronlO-

- UAAACACUUCUGAGAAA 17

737 19623

CFTR-lntronlO-

+ UAAACAAACAAAGGAAA 17

738 19624

CFTR-lntronlO-

+ AUUAUCUUUCUAGUAAA 17

739 19625

CFTR-lntronlO-

+ ACCAAAUAAACAAACAA 17

740 19626

CFTR-lntronlO-

- AUGGAUAAGUUGAACAA 17

741 19627

CFTR-lntronlO-

- AUUAGGAAAAUGUACAA 17

742 19628

CFTR-lntronlO-

+ UG U U UAAAUAU U CCCAA 17

743 19629

CFTR-lntronlO-

+ A A AG A A U A AG G C A U C A A 17

744 19630

CFTR-lntronlO-

+ AAAUAUAUU CAAA AG A A 17

745 19631

CFTR-lntronlO-

+ UGAGAGACAGUAAAGAA 17

746 19632

CFTR-lntronlO-

- AAGGAAAUGAGGAAGAA 17

747 19633

645

5535.1 CFTR-lntronlO-

+ AGGCUGAGGCAGGAGAA 17

748 19634

CFTR-lntronlO-

+ AAACUGAGUAGAAGGAA 17

749 19635

CFTR-lntronlO-

+ U UUCUCUUUACUGUGAA 17

750 19636

CFTR-lntronlO-

+ A AG A A A AG U A U C A A U A A 17

751 19637

CFTR-lntronlO-

+ CAG UG ACU U CAU AAU AA 17

752 19638

CFTR-lntronlO-

+ AUAGAGAAAACUCAUAA 17

753 19639

CFTR-lntronlO-

+ ACAAAAAUUAAAACUAA 17

754 19640

CFTR-lntronlO-

+ U CU AG AAAACAAUG U AA 17

755 19641

CFTR-lntronlO-

- AG AU AAAG U UG AAU U AA 17

756 19642

CFTR-lntronlO-

+ AAGCCUGUAUUGUUUAA 17

757 19643

CFTR-lntronlO-

- AUUUUGACCAUUU UUAA 17

758 19644

CFTR-lntronlO-

+ UACCAUCCUGGCCAACA 17

759 19645

CFTR-lntronlO-

- UUAUAGCAGCCUGAACA 17

760 19646

CFTR-lntronlO-

- UU UAAACAGAAGUAACA 17

761 19647

CFTR-lntronlO-

+ AGAGAGAACUGCUCACA 17

762 19648

CFTR-lntronlO-

+ CCUGCUGUGUUCUCACA 17

763 19649

CFTR-lntronlO-

- UGAAAUCCUAAUUCCCA 17

764 19650

CFTR-lntronlO-

- UUUAUUUUUAUAUUCCA 17

765 19651

CFTR-lntronlO-

- AGACAAGGGAGGAAGCA 17

766 19652

CFTR-lntronlO-

+ UCAACAUAUGAAUGGCA 17

767 19653

CFTR-lntronlO-

- UACAGGCUUGAACUGCA 17

768 19654

646

5535.1 CFTR-lntronlO-

- AAGGUGAUGGUAUUGCA 17

769 19655

CFTR-lntronlO-

+ CU AU U U AAACAG AAU CA 17

770 19656

CFTR-lntronlO-

+ UGGGAAGUCCAAGAUCA 17

771 19657

CFTR-lntronlO-

+ UUCACUAAAAUAAUUCA 17

772 19658

CFTR-lntronlO-

+ UAUAUUUUAUGCAUUCA 17

773 19659

CFTR-lntronlO-

- AUAAGCCACACAGUUCA 17

774 19660

CFTR-lntronlO-

+ U UGAGCCCAGGAGUUCA 17

775 19661

CFTR-lntronlO-

+ AAUUGGUACAAAUUUCA 17

776 19662

CFTR-lntronlO-

- AGAGGAAGGAAGAAAGA 17

777 19663

CFTR-lntronlO-

- AG A U U C U A A AG G A A AG A 17

778 19664

CFTR-lntronlO-

- AAG G AAG G AAG G AAAG A 17

779 19665

CFTR-lntronlO-

+ UGUAUUUUUAGUAGAGA 17

780 19666

CFTR-lntronlO-

- UUUUUUUUU UUUUGAGA 17

781 19667

CFTR-lntronlO-

- CUUUUCCUCUUAAUAGA 17

782 19668

CFTR-lntronlO-

+ A U A U U C A A A AG AAAG G A 17

783 19669

CFTR-lntronlO-

- AAGGAAGGAAAGAAGGA 17

784 19670

CFTR-lntronlO-

+ CACUGUGUUAGCCAGGA 17

785 19671

CFTR-lntronlO-

- CACCAUGUUGGCCAGGA 17

786 19672

CFTR-lntronlO-

- AAGGCAGAGUUAGAGGA 17

787 19673

CFTR-lntronlO-

- AAAAUUAUACUAUAGGA 17

788 19674

CFTR-lntronlO-

- AUAGAGUAAGACAGGGA 17

789 19675

647

5535.1 CFTR-lntronlO-

- CACCGUUU UAGCCGGGA 17

790 19676

CFTR-lntronlO-

- UGGACUGAGUAACUGGA 17

791 19677

CFTR-lntronlO-

- AUAUAUGUGUGUCUGGA 17

792 19678

CFTR-lntronlO-

- AGGUGAUUAGUCCAUGA 17

793 19679

CFTR-lntronlO-

+ UGGCAUAGCUGCACUGA 17

794 19680

CFTR-lntronlO-

- AAAUUAGCCAGACGUGA 17

795 19681

CFTR-lntronlO-

- CCUAAUUCCCAAGGUGA 17

796 19682

CFTR-lntronlO-

- AGACUUGCAGGAGGUGA 17

797 19683

CFTR-lntronlO-

+ AUGGCAGAAAGGGGUGA 17

798 19684

CFTR-lntronlO-

- UUCAGGACAUGCUUUGA 17

799 19685

CFTR-lntronlO-

+ U UCAAUUCUUCAAAAUA 17

800 19686

CFTR-lntronlO-

+ AGUAUAUCAAAAGAAUA 17

801 19687

CFTR-lntronlO-

+ CCUCUGUGCUUUGAAUA 17

802 19688

CFTR-lntronlO-

- AUAAAUGUUGAAUAAUA 17

803 19689

CFTR-lntronlO-

- CAUAGUAUUCUAUCAUA 17

804 19690

CFTR-lntronlO-

+ CAUAGAGAAAACUCAUA 17

805 19691

CFTR-lntronlO-

+ CUGCAGACCUCAAUAUA 17

806 19692

CFTR-lntronlO-

- AAGUUUCUCAUCUUAUA 17

807 19693

CFTR-lntronlO-

+ CCGAGUAGCUGGGACUA 17

808 19694

CFTR-lntronlO-

- UGGUUUGAAGAACAGUA 17

809 19695

CFTR-lntronlO-

- UGUUUAUGUUAUCUGUA 17

810 19696

648

5535.1 CFTR-lntronlO-

- UUUUAGGCUAUUCUGUA 17

811 19697

CFTR-lntronlO-

+ ACUAGUGGCACUUUGUA 17

812 19698

CFTR-lntronlO-

+ U UAGUUUUAUGCCAUUA 17

813 19699

CFTR-lntronlO-

- CAGGAGGUGAGGGAUUA 17

814 19700

CFTR-lntronlO-

- ACU UCCUGUUGCUAUUA 17

815 19701

CFTR-lntronlO-

- UGUAUAUGUGUGUAUUA 17

816 19702

CFTR-lntronlO-

+ AUGUUAUUCAAGGUUUA 17

817 19703

CFTR-lntronlO-

- CAU UUUGACCAU UUUUA 17

818 19704

CFTR-lntronlO-

- AAGAUAAUGGGAGAAAC 17

819 19705

CFTR-lntronlO-

+ UGUGGCUUAUAAACAAC 17

820 19706

CFTR-lntronlO-

- U U U U AAACAG AAG U AAC 17

821 19707

CFTR-lntronlO-

- AAACUGUUAUAAUUAAC 17

822 19708

CFTR-lntronlO-

- UGACCCUUAAACAAUAC 17

823 19709

CFTR-lntronlO-

+ CAAGUAGCUGGGACUAC 17

824 19710

CFTR-lntronlO-

+ CGAGUAGCUGGGACUAC 17

825 19711

CFTR-lntronlO-

- CAAAGUGCUGGGAUUAC 17

826 19712

CFTR-lntronlO-

- CAAAGUGUUGGGAUUAC 17

827 19713

CFTR-lntronlO-

+ UGCAAUAUGCAAUUUAC 17

828 19714

CFTR-lntronlO-

+ AAAUAUUGACUAUUUAC 17

829 19715

CFTR-lntronlO-

- UAUAUAUAUUUUUAACC 17

830 19716

CFTR-lntronlO-

- AGAGUCUUACUGUCACC 17

831 19717

649

5535.1 CFTR-lntronlO-

+ U ACU AAAAAAAG U U ACC 17

832 19718

CFTR-lntronlO-

+ AAAGGUCAAUUGAGCCC 17

833 19719

CFTR-lntronlO-

- UGCAAGCUCCGCCUCCC 17

834 19720

CFTR-lntronlO-

- UGCAACCUCUGCCUCCC 17

835 19721

CFTR-lntronlO-

+ ACCACUGUGCUCCAGCC 17

836 19722

CFTR-lntronlO-

+ ACCACUGAAGUUCAGCC 17

837 19723

CFTR-lntronlO-

+ AAUACAAAAAAUUAGCC 17

838 19724

CFTR-lntronlO-

+ AAGAAAUGAAACAGGCC 17

839 19725

CFTR-lntronlO-

+ AGAGAUCAAUACCAUCC 17

840 19726

CFTR-lntronlO-

- UGAUGGUGGCUUGAUCC 17

841 19727

CFTR-lntronlO-

+ CGCUGGUCUCAAACUCC 17

842 19728

CFTR-lntronlO-

- CUGUAACCUUGAACUCC 17

843 19729

CFTR-lntronlO-

- CUGCAAGCUCCGCCUCC 17

844 19730

CFTR-lntronlO-

- CUGCAACCUCUGCCUCC 17

845 19731

CFTR-lntronlO-

+ CUGCAAGUUCUGCCUCC 17

846 19732

CFTR-lntronlO-

- CCAUG U G AG AACACAG C 17

847 19733

CFTR-lntronlO-

- CAC AG C AG G AAG ACAG C 17

848 19734

CFTR-lntronlO-

- AGUGCAGCUAUGCCAGC 17

849 19735

CFTR-lntronlO-

- U U U U AAAACAAAAU AGC 17

850 19736

CFTR-lntronlO-

- AAACAAAAGAAAAUAGC 17

851 19737

CFTR-lntronlO-

- UCACCCUCCCAAGUAGC 17

852 19738

650

5535.1 CFTR-lntronlO-

+ UCAGCCUCCCAAGUAGC 17

853 19739

CFTR-lntronlO-

- AG AG U CU U CCAAG U AG C 17

854 19740

CFTR-lntronlO-

+ UCAGCCUCCCGAGUAGC 17

855 19741

CFTR-lntronlO-

+ AAA U AC A A A A A A U U AG C 17

856 19742

CFTR-lntronlO-

+ UGCCAUGUUGCCCACGC 17

857 19743

CFTR-lntronlO-

+ UAAGAAAUGAAACAGGC 17

858 19744

CFTR-lntronlO-

- UCU UACUGUCACCAGGC 17

859 19745

CFTR-lntronlO-

- CGCUCUGUCGCCCAGGC 17

860 19746

CFTR-lntronlO-

- CUU UUGGAGGCAGAGGC 17

861 19747

CFTR-lntronlO-

+ CUUUGGGAGGCCGAGGC 17

862 19748

CFTR-lntronlO-

+ CUCACAGUUCUGGAGGC 17

863 19749

CFTR-lntronlO-

- AAGGAGGUCACUGAGGC 17

864 19750

CFTR-lntronlO-

- ACUCGGGAGGCUGAGGC 17

865 19751

CFTR-lntronlO-

+ ACUUGGGAGGCUGAGGC 17

866 19752

CFTR-lntronlO-

+ ACU UGGGAGGGUGAGGC 17

867 19753

CFTR-lntronlO-

- UUCAAGGAAGAGGGGGC 17

868 19754

CFTR-lntronlO-

+ U UCAACAUAUGAAUGGC 17

869 19755

CFTR-lntronlO-

- UAGCCAGACGUGAUGGC 17

870 19756

CFTR-lntronlO-

+ UAGCCGGGCGUAGUGGC 17

871 19757

CFTR-lntronlO-

- UCAGCCUCCCAAAGUGC 17

872 19758

CFTR-lntronlO-

- UCGGCCUCCCAAAGUGC 17

873 19759

651

5535.1 CFTR-lntronlO-

- CAAGGUGAUGGUAUUGC 17

874 19760

CFTR-lntronlO-

- UU UGAACAAAGACUUGC 17

875 19761

CFTR-lntronlO-

- CGUAGUCCCAGCUACUC 17

876 19762

CFTR-lntronlO-

+ CUCCACU UCUCAGGCUC 17

877 19763

CFTR-lntronlO-

+ AUAGAGAGAAACAUCUC 17

878 19764

CFTR-lntronlO-

+ UGCAGCCUCCACU UCUC 17

879 19765

CFTR-lntronlO-

+ AGAGACAAGGUGGUGUC 17

880 19766

CFTR-lntronlO-

- UCAAUAAAUUUGGUGUC 17

881 19767

CFTR-lntronlO-

- AUGUAUAUAUGUGUGUC 17

882 19768

CFTR-lntronlO-

+ UCU UUCUAAU UUCAUUC 17

883 19769

CFTR-lntronlO-

- AGGAAGUGAUCAGAUUC 17

884 19770

CFTR-lntronlO-

+ UAAGAGGAAAAGACUUC 17

885 19771

CFTR-lntronlO-

+ UUUAUUUCUCACAGUUC 17

886 19772

CFTR-lntronlO-

+ UGUGUGUGUCCUUGUUC 17

887 19773

CFTR-lntronlO-

- ACUGGCAAUUAAAUUUC 17

888 19774

CFTR-lntronlO-

- UCU UUUGAAUAUAUU UC 17

889 19775

CFTR-lntronlO-

+ AUAAAUAAUUGCCUUUC 17

890 19776

CFTR-lntronlO-

- AUUAUAACACUGCUU UC 17

891 19777

CFTR-lntronlO-

+ AAAAUUUGUUUUCUU UC 17

892 19778

CFTR-lntronlO-

+ AAAAACAUUAGCCAAAG 17

893 19779

CFTR-lntronlO-

+ UCUCACAUGGCAG A A AG 17

894 19780

652

5535.1 CFTR-lntronlO-

- U UGAU AAG AAGAG AAAG 17

895 19781

CFTR-lntronlO-

- A AG A U U C U A A AG G A A AG 17

896 19782

CFTR-lntronlO-

- UGAAUUUUUUUUCCAAG 17

897 19783

CFTR-lntronlO-

- CACCUGAGCCUGAGAAG 17

898 19784

CFTR-lntronlO-

+ ACU UUGGGAGGCUGAAG 17

899 19785

CFTR-lntronlO-

+ A A A A A U U C AC A A A U A AG 17

900 19786

CFTR-lntronlO-

- AAAU U AG AAAG AAU AAG 17

901 19787

CFTR-lntronlO-

- A A A A A U A A A A A U A U A AG 17

902 19788

CFTR-lntronlO-

- AGAAGGAAGGAAGUAAG 17

903 19789

CFTR-lntronlO-

- C C A U A U U C A A AG C AC AG 17

904 19790

CFTR-lntronlO-

- ACCAGGCUGGAGCACAG 17

905 19791

CFTR-lntronlO-

+ UUAAUGGCUGUGCACAG 17

906 19792

CFTR-lntronlO-

- UAUGAGAAAAGUCACAG 17

907 19793

CFTR-lntronlO-

+ CCUAGGCUAGGGUACAG 17

908 19794

CFTR-lntronlO-

+ UGUUUAAAACUCUCCAG 17

909 19795

CFTR-lntronlO-

- CUAUAUUUGUUUUCCAG 17

910 19796

CFTR-lntronlO-

+ AG G AAAG GAG G U AG CAG 17

911 19797

CFTR-lntronlO-

+ UUGAGCCCGGGAGGCAG 17

912 19798

CFTR-lntronlO-

- AGCACU UUUGGAGGCAG 17

913 19799

CFTR-lntronlO-

+ CAACAUAUGAAUGGCAG 17

914 19800

CFTR-lntronlO-

+ CCCAGGCUAGAGUGCAG 17

915 19801

653

5535.1 CFTR-lntronlO-

- CCCAGGCUGGAGUGCAG 17

916 19802

CFTR-lntronlO-

- UGUCAGGCUGGGUGCAG 17

917 19803

CFTR-lntronlO-

+ U AU U U AAACAG AAU CAG 17

918 19804

CFTR-lntronlO-

- AAUGUUAAUUUAUU CAG 17

919 19805

CFTR-lntronlO-

- CCCAGGCUGAACUUCAG 17

920 19806

CFTR-lntronlO-

+ U UGUUACAUAAAAAGAG 17

921 19807

CFTR-lntronlO-

- AACAGAAAAAGAAAGAG 17

922 19808

CFTR-lntronlO-

- AAAUUAUACUAUAGGAG 17

923 19809

CFTR-lntronlO-

+ AAUAGCCUAUUGUUGAG 17

924 19810

CFTR-lntronlO-

- UAAAUGUUGAAUAAUAG 17

925 19811

CFTR-lntronlO-

+ UAGAUGAUUAUUAAUAG 17

926 19812

CFTR-lntronlO-

- UAAAAAGUGAUCUCUAG 17

927 19813

CFTR-lntronlO-

+ AAAUUAGCCGGGCGUAG 17

928 19814

CFTR-lntronlO-

- UAUGAAGGCAGAGUUAG 17

929 19815

CFTR-lntronlO-

+ AGAUGAUUAGCAUCACG 17

930 19816

CFTR-lntronlO-

- UAUUUUUAGUAGAGACG 17

931 19817

CFTR-lntronlO-

+ AACACUUUGGGAGGCCG 17

932 19818

CFTR-lntronlO-

+ AGCACUUUGGGAGGCCG 17

933 19819

CFTR-lntronlO-

+ AUGAAACAGGCCGGGCG 17

934 19820

CFTR-lntronlO-

+ A A A A A A A A A U C A A A AG G 17

935 19821

CFTR-lntronlO-

+ CUGAGUAGAAGGAAAGG 17

936 19822

654

5535.1 CFTR-lntronlO-

- U UUGAAGAACAG UAAGG 17

937 19823

CFTR-lntronlO-

- AAUGGCGUGAACCCAGG 17

938 19824

CFTR-lntronlO-

- UAGUUUCAAGGAAGAGG 17

939 19825

CFTR-lntronlO-

+ U U ACAU AAAAAG AG AGG 17

940 19826

CFTR-lntronlO-

+ UGUGUUUUU UGUAGAGG 17

941 19827

CFTR-lntronlO-

+ ACU UUGGGAGGCCGAGG 17

942 19828

CFTR-lntronlO-

- UACUUGGGAGGCUGAGG 17

943 19829

CFTR-lntronlO-

- AAAAAUUAUACUAUAGG 17

944 19830

CFTR-lntronlO-

+ AAACAGGCCGGGCGCGG 17

945 19831

CFTR-lntronlO-

- CUGUAGGGAGACAAGGG 17

946 19832

CFTR-lntronlO-

+ AAUGGCGUGAACCCGGG 17

947 19833

CFTR-lntronlO-

+ AAUUGCUUGAGCCCGGG 17

948 19834

CFTR-lntronlO-

+ UGGGAGGCCGAGGCGGG 17

949 19835

CFTR-lntronlO-

- AGUCCCAGCUACUCGGG 17

950 19836

CFTR-lntronlO-

- UGGGAGGCUGAGGUGGG 17

951 19837

CFTR-lntronlO-

+ AGUCCCAGCUACUUGGG 17

952 19838

CFTR-lntronlO-

+ AAUCCCAACACUU UGGG 17

953 15660

CFTR-lntronlO-

+ AAACCCAGCACUUUGGG 17

954 19839

CFTR-lntronlO-

+ AAUCCCAGCACUUUGGG 17

955 19840

CFTR-lntronlO-

- AGGGUGGGGCCUUUGGG 17

956 19841

CFTR-lntronlO-

- CAGGCAAGUGAUGAUGG 17

957 19842

655

5535.1 CFTR-lntronlO-

- UUAGCCAGACGUGAUGG 17

958 19843

CFTR-lntronlO-

+ AUUUCUCACAGUUCUGG 17

959 19844

CFTR-lntronlO-

- CUGAGCCUGAGAAGUGG 17

960 19845

CFTR-lntronlO-

- AGGCUGGAGUGCAGUGG 17

961 19846

CFTR-lntronlO-

+ U UAGCCGGGCGUAGUGG 17

962 19847

CFTR-lntronlO-

- AAAAUAGCUGGGUGUGG 17

963 19848

CFTR-lntronlO-

+ UCAAAAAAUAUUUGUGG 17

964 19849

CFTR-lntronlO-

- AAUCCUAGCACUUUUGG 17

965 19850

CFTR-lntronlO-

- AAUUUUAUAUAGAAAUG 17

966 19851

CFTR-lntronlO-

+ AACAAACAAAGGAAAUG 17

967 19852

CFTR-lntronlO-

- AAGCUAGUGAAUGAAUG 17

968 19853

CFTR-lntronlO-

+ AUUAUUCAACAUUUAUG 17

969 19854

CFTR-lntronlO-

- CAGUAAGGAGGUCACUG 17

970 19855

CFTR-lntronlO-

- AGCUACUCGGGAGGCUG 17

971 19856

CFTR-lntronlO-

+ AGCUACUUGGGAGGCUG 17

972 19857

CFTR-lntronlO-

+ C A A A A A UUAGCUGAGUG 17

973 19858

CFTR-lntronlO-

+ A C A U A A A A AG AG AG G U G 17

974 19859

CFTR-lntronlO-

+ UGUUUUUUGUAGAGGUG 17

975 19860

CFTR-lntronlO-

- AAGACUUGCAGGAGGUG 17

976 19861

CFTR-lntronlO-

+ AGCUACUUGGGAGGGUG 17

977 19862

CFTR-lntronlO-

+ CAUGGCAGAAAGGGGUG 17

978 19863

656

5535.1 CFTR-lntronlO-

- AAGAAAAUAGCUGGGUG 17

979 19864

CFTR-lntronlO-

+ AAAUACCAUGAACUGUG 17

980 19865

CFTR-lntronlO-

- U U U AU AAAAAAU AAU UG 17

981 19866

CFTR-lntronlO-

+ U AU U C AAAAAAU AU U UG 17

982 19867

CFTR-lntronlO-

- ACAUUGGAAAAUUUUUG 17

983 19868

CFTR-lntronlO-

- UAGUAGUUAAGUUUUUG 17

984 19869

CFTR-lntronlO-

- U C A A A A A A A A A A A A A A U 17

985 19870

CFTR-lntronlO-

+ UAAAAUGACAAUCAAAU 17

986 19871

CFTR-lntronlO-

+ CUAUUUGGAUGUCAAAU 17

987 19872

CFTR-lntronlO-

+ AAACAAACAAAGGAAAU 17

988 19873

CFTR-lntronlO-

- UUGAAGGAAGAUCCAAU 17

989 19874

CFTR-lntronlO-

- CAUAAAUGUUGAAUAAU 17

990 19875

CFTR-lntronlO-

- U U U ACU AG AAAG AU AAU 17

991 19876

CFTR-lntronlO-

- ACUG U CAG AG AAG U AAU 17

992 19877

CFTR-lntronlO-

- UUUUUCAGUUAAUACAU 17

993 19878

CFTR-lntronlO-

+ UACAAUUCUUAUUACAU 17

994 19879

CFTR-lntronlO-

- ACAGGCUUGAACUGCAU 17

995 19880

CFTR-lntronlO-

- ACCCUAGCCUAGGUGAU 17

996 19881

CFTR-lntronlO-

+ U UGUGUUAACAAAAUAU 17

997 19882

CFTR-lntronlO-

+ AAUAUAUAUAUGCAUAU 17

998 19883

CFTR-lntronlO-

- U U AAAAAAU U AU ACU AU 17

999 19884

657

5535.1 CFTR-lntronlO-

- AAAGUUUCUCAUCUUAU 17

1000 19885

CFTR-lntronlO-

+ UAUUAUUCAACAUUUAU 17

1001 19886

CFTR-lntronlO-

- CAAAGUGCUGGGUU UAU 17

1002 19887

CFTR-lntronlO-

+ UCAGACUUUUAUUUUAU 17

1003 19888

CFTR-lntronlO-

+ U U U AACAAACCU U U U AU 17

1004 19889

CFTR-lntronlO-

+ UUCCAAAUUUUU UUUAU 17

1005 19890

CFTR-lntronlO-

- UUAUUCUUGUAAUAACU 17

1006 19891

CFTR-lntronlO-

- CCGUAGUCCCAGCUACU 17

1007 19892

CFTR-lntronlO-

+ CUGUAGUCCCAGCUACU 17

1008 19893

CFTR-lntronlO-

+ CUGCAAUACCAUCACCU 17

1009 19894

CFTR-lntronlO-

+ CCACUGCACUCCAGCCU 17

1010 19895

CFTR-lntronlO-

+ CCACUGAAGUUCAGCCU 17

1011 19896

CFTR-lntronlO-

- CCACUGUACCCUAGCCU 17

1012 19897

CFTR-lntronlO-

- CCACUGCACUCUAGCCU 17

1013 19898

CFTR-lntronlO-

- UCGUGAUCCGCCCGCCU 17

1014 19899

CFTR-lntronlO-

- UCAUGAUCUGCCUGCCU 17

1015 19900

CFTR-lntronlO-

- UGUAACCUUGAACUCCU 17

1016 19901

CFTR-lntronlO-

+ UGCAAGUUCUGCCUCCU 17

1017 19902

CFTR-lntronlO-

- AGGUUUUGGAUGGAGCU 17

1018 19903

CFTR-lntronlO-

- A AC A A A AG A A A A U AG C U 17

1019 19904

CFTR-lntronlO-

- CACCCUCCCAAGUAGCU 17

1020 19905

658

5535.1 CFTR-lntronlO-

+ CAGCCUCCCAAGUAGCU 17

1021 19906

CFTR-lntronlO-

+ CAGCCUCCCGAGUAGCU 17

1022 19907

CFTR-lntronlO-

+ UCACAGUUCUGGAGGCU 17

1023 19908

CFTR-lntronlO-

- AAAUUAUUUCUACUGCU 17

1024 19909

CFTR-lntronlO-

+ CUGCCUCCAAAAGUGCU 17

1025 19910

CFTR-lntronlO-

- CAGCCUCCCAAAGUGCU 17

1026 19911

CFTR-lntronlO-

- CGGCCUCCCAAAGUGCU 17

1027 19912

CFTR-lntronlO-

- AAAAAAG UUGAGUUGCU 17

1028 19913

CFTR-lntronlO-

- UGCUGGCACCUUGAUCU 17

1029 19914

CFTR-lntronlO-

- UGCUUUUCCCACUAUCU 17

1030 19915

CFTR-lntronlO-

+ AAUUUGAACAACAUUCU 17

1031 19916

CFTR-lntronlO-

+ U UUUUCAUUAUGAUUCU 17

1032 19917

CFTR-lntronlO-

+ CUUUUUCUUAAUUUUCU 17

1033 19918

CFTR-lntronlO-

- UGAGGAAGAAAGGAAGU 17

1034 19919

CFTR-lntronlO-

- UCUGCAAUUGUAUCAGU 17

1035 19920

CFTR-lntronlO-

+ CAGUUUUAUUUU UCAGU 17

1036 19921

CFTR-lntronlO-

+ ACAUUUUCCUAAUGAGU 17

1037 19922

CFTR-lntronlO-

- AGUGGAAGUAGUAUAGU 17

1038 19923

CFTR-lntronlO-

+ U ACAU AAAAAG AG AGG U 17

1039 19924

CFTR-lntronlO-

- UUAGAGGUUAAGGAGGU 17

1040 19925

CFTR-lntronlO-

- ACUUGGGAGGCUGAGGU 17

1041 19926

659

5535.1 CFTR-lntronlO-

- ACGGGGUUUCACCAUGU 17

1042 19927

CFTR-lntronlO-

- UCGGCCUCCCAAAGUGU 17

1043 19928

CFTR-lntronlO-

- AGAAGAGAAAGGGGUGU 17

1044 19929

CFTR-lntronlO-

- ACCCAAU AAAAAAAAU U 17

1045 19930

CFTR-lntronlO-

- U U U CCACU CAAUAAAU U 17

1046 19931

CFTR-lntronlO-

+ CCAUCACCUUGGGAAUU 17

1047 19932

CFTR-lntronlO-

- CACUAUUGAUUGACAUU 17

1048 19933

CFTR-lntronlO-

+ CAAGGUGCCAGCAGAUU 17

1049 19934

CFTR-lntronlO-

- UAUUCUUUUUAGAGAUU 17

1050 19935

CFTR-lntronlO-

- UACUUUUCUUCCUGAU U 17

1051 19936

CFTR-lntronlO-

- UUUUCAUUGAAUGUAUU 17

1052 19937

CFTR-lntronlO-

- UCCUU UGUUUGUUUAUU 17

1053 19938

CFTR-lntronlO-

+ CAGACUUUUAUUUUAU U 17

1054 19939

CFTR-lntronlO-

+ UCCAAAUUUUUU UUAUU 17

1055 19940

CFTR-lntronlO-

+ CUGUAAUCCCAACACUU 17

1056 19941

CFTR-lntronlO-

- AAGUAACAGGGCCACUU 17

1057 19942

CFTR-lntronlO-

+ CUAUAAACCCAGCACUU 17

1058 19943

CFTR-lntronlO-

+ CUGUAAUCCCAGCACUU 17

1059 19944

CFTR-lntronlO-

- AAUUGAAUAUGAGACUU 17

1060 19945

CFTR-lntronlO-

+ UGUAGUCCCAGCUACUU 17

1061 19946

CFTR-lntronlO-

+ UGCAAUACCAUCACCUU 17

1062 19947

660

5535.1 CFTR-lntronlO-

+ AUGUUAAAUUUUCCCUU 17

1063 19948

CFTR-lntronlO-

+ U UCCCU UAGGAUAUCU U 17

1064 19949

CFTR-lntronlO-

- AAGCAAGGAGAUGAGUU 17

1065 19950

CFTR-lntronlO-

- CGGCCUCCCAAAGUGUU 17

1066 19951

CFTR-lntronlO-

- UGUUAUCUCUGAAAUU U 17

1067 19952

CFTR-lntronlO-

- UUUGAUUAGAUAAAUU U 17

1068 19953

CFTR-lntronlO-

- UCAAUAUUUUGGAAUU U 17

1069 19954

CFTR-lntronlO-

- ACUAUUGAUUGACAUU U 17

1070 19955

CFTR-lntronlO-

+ AAGGUGCCAGCAGAUUU 17

1071 19956

CFTR-lntronlO-

- UAGUUUUAUCAAUAUU U 17

1072 19957

CFTR-lntronlO-

+ UCUCUGCAAACAUAUUU 17

1073 19958

CFTR-lntronlO-

- CAU UAUUCAUGAUAUUU 17

1074 19959

CFTR-lntronlO-

- UUUCAUUGAAUGUAUUU 17

1075 19960

CFTR-lntronlO-

+ UGUAAUCCCAACACUUU 17

1076 19961

CFTR-lntronlO-

+ UAUAAACCCAGCACUUU 17

1077 19962

CFTR-lntronlO-

+ UGUAAUCCCAGCACUUU 17

1078 19963

CFTR-lntronlO-

- UGUAAUCCUAGCACUUU 17

1079 19964

CFTR-lntronlO-

- UGCAGGGUGGGGCCUU U 17

1080 19965

CFTR-lntronlO-

- UUUAACUGAAUAUCUUU 17

1081 19966

CFTR-lntronlO-

- AUGGGAGAAACAGGUUU 17

1082 19967

CFTR-lntronlO-

- AUACAUUGGAAAAUUU U 17

1083 19968

661

5535.1 CFTR-lntronlO-

- CAAUAUUUUGGAAUUU U 17

1084 19969

CFTR-lntronlO-

- U ACAU UGG AAAAU U U U U 17

1085 19970

CFTR-lntronlO-

- CUUUGGCUAAUGUUUUU 17

1086 19971

CFTR-lntronlO-

- CACUU UAUAGUUU UUUU 17

1087 19972

CFTR-lntronlO-

+ ACAAACAAAGAAACAAAAAA 20

1088 19973

CFTR-lntronlO-

+ ACAUAUGAUUUUAUGAAAAA 20

1089 19974

CFTR-lntronlO-

+ CGAGACCAUCCCGGCUAAAA 20

1090 19975

CFTR-lntronlO-

- UAGAAAGAAAAAACAGCAAA 20

1091 19976

CFTR-lntronlO-

+ AU U AG U AAAAAAAAAU CAAA 20

1092 19977

CFTR-lntronlO-

+ AAG AAAAG CUG AAAG U CAAA 20

1093 19978

CFTR-lntronlO-

+ UACAUUCAAUGAAAAAGAAA 20

1094 19979

CFTR-lntronlO-

- AGGGUUGAUAAGAAGAGAAA 20

1095 19980

CFTR-lntronlO-

- AUUUAAACACUUCUGAGAAA 20

1096 19981

CFTR-lntronlO-

+ AAAUAAACAAACAAAGGAAA 20

1097 19982

CFTR-lntronlO-

- AAGGAUGUUUAUUUAUGAAA 20

1098 19983

CFTR-lntronlO-

+ AAAACCAAAUAAACAAACAA 20

1099 19984

CFTR-lntronlO-

- CUCAUUAGGAAAAUGUACAA 20

1100 19985

CFTR-lntronlO-

+ AUGGACUAAUCACCUCCCAA 20

1101 19986

CFTR-lntronlO-

- UCAUGUUGAUAAAGGGUCAA 20

1102 19987

CFTR-lntronlO-

+ CUGAAAUAUAUU CAAA AG A A 20

1103 19988

CFTR-lntronlO-

+ AGAUGAGAGACAGUAAAGAA 20

1104 19989

662

5535.1 CFTR-lntronlO-

- AAGAAGGAAAUGAGGAAGAA 20

1105 19990

CFTR-lntronlO-

+ UGUGUUCUCACAUGGCAGAA 20

1106 19991

CFTR-lntronlO-

+ U UUGGGAGGCUGAAGCGGAA 20

1107 19992

CFTR-lntronlO-

+ UUAGGAUUUCAACAUAUGAA 20

1108 19993

CFTR-lntronlO-

+ ACAUUUCUCUUUACUGUGAA 20

1109 19994

CFTR-lntronlO-

+ AGGAAGAAAAGUAUCAAUAA 20

1110 19995

CFTR-lntronlO-

+ AUACAGUGACUUCAUAAUAA 20

1111 19996

CFTR-lntronlO-

+ AACAUAGAGAAAACUCAUAA 20

1112 19997

CFTR-lntronlO-

+ UGAACAAAAAUUAAAACUAA 20

1113 19998

CFTR-lntronlO-

+ UUUUCUAGAAAACAAUGUAA 20

1114 19999

CFTR-lntronlO-

- AACAG AU AAAG U UG AAU U AA 20

1115 20000

CFTR-lntronlO-

+ UGUUACCUU UCAAUGUUUAA 20

1116 20001

CFTR-lntronlO-

+ UUCAAGCCUGUAUUGUUUAA 20

1117 20002

CFTR-lntronlO-

- AUCAUUUUGACCAUUUUUAA 20

1118 20003

CFTR-lntronlO-

+ CAAUACCAUCCUGGCCAACA 20

1119 20004

CFTR-lntronlO-

- UGAGACCAGCGUGGGCAACA 20

1120 20005

CFTR-lntronlO-

- UUGUUAUAGCAGCCUGAACA 20

1121 20006

CFTR-lntronlO-

+ UGGAGAGAGAACUGCUCACA 20

1122 20007

CFTR-lntronlO-

+ CUUCCUGCUGUGUUCUCACA 20

1123 20008

CFTR-lntronlO-

+ AAUGAUCAAUAAUAGAGACA 20

1124 20009

CFTR-lntronlO-

+ AUUUUACAAUUCUUAUUACA 20

1125 20010

663

5535.1 CFTR-lntronlO-

- UGUUGAAAUCCUAAUUCCCA 20

1126 20011

CFTR-lntronlO-

- UUCUUUAUU UUUAUAUUCCA 20

1127 20012

CFTR-lntronlO-

+ AUUUCAACAUAUGAAUGGCA 20

1128 20013

CFTR-lntronlO-

- AAAGUGCCACUAGUGAUGCA 20

1129 20014

CFTR-lntronlO-

- CAA U ACAG G C U U G AAC U G CA 20

1130 20015

CFTR-lntronlO-

- CCCAAGGUGAUGGUAU UGCA 20

1131 20016

CFTR-lntronlO-

+ AGGGUACAGUGGUGCAAUCA 20

1132 20017

CFTR-lntronlO-

+ UGCUUCACUAAAAUAAUUCA 20

1133 20018

CFTR-lntronlO-

+ ACAUAUAUUUUAUGCAUUCA 20

1134 20019

CFTR-lntronlO-

- UUUAUAAGCCACACAGUUCA 20

1135 20020

CFTR-lntronlO-

+ CAAUUGAGCCCAGGAGUUCA 20

1136 20021

CFTR-lntronlO-

- AAGAGAGGAAGGAAGAAAGA 20

1137 20022

CFTR-lntronlO-

- AGGAAGGAAGGAAGGAAAGA 20

1138 20023

CFTR-lntronlO-

- A A AG A AG G A AG G A AG U A AG A 20

1139 20024

CFTR-lntronlO-

- AAUGAAAGCAAUAGUAGAGA 20

1140 20025

CFTR-lntronlO-

+ UUUUGUAUUUUUAGUAGAGA 20

1141 20026

CFTR-lntronlO-

- UUUUUUUUU UUUUUUUGAGA 20

1142 20027

CFTR-lntronlO-

- AGUCUUUUCCUCUUAAUAGA 20

1143 20028

CFTR-lntronlO-

+ AAUAUAUU CAA A AG A A AG G A 20

1144 20029

CFTR-lntronlO-

- AG G AAG G AAG G AAAG AAG G A 20

1145 20030

CFTR-lntronlO-

- AAAGGAAGUAGGAGGAAGGA 20

1146 20031

664

5535.1 CFTR-lntronlO-

+ U UUCACUGUGUUAGCCAGGA 20

1147 20032

CFTR-lntronlO-

- UU UCACCAUGUUGGCCAGGA 20

1148 20033

CFTR-lntronlO-

- ACAGAAAAAGAAAGAGAGGA 20

1149 20034

CFTR-lntronlO-

- AUGAAGGCAGAGUUAGAGGA 20

1150 20035

CFTR-lntronlO-

- UAAAAAAUUAUACUAUAGGA 20

1151 20036

CFTR-lntronlO-

+ AUUGGUACAAAUUUCAGGGA 20

1152 20037

CFTR-lntronlO-

- UU UCACCGUUUUAGCCGGGA 20

1153 20038

CFTR-lntronlO-

- AUAGUAUUCUAUCAUAUGGA 20

1154 20039

CFTR-lntronlO-

- UUCUGGACUGAGUAACUGGA 20

1155 20040

CFTR-lntronlO-

- UGUAUAUAUGUGUGUCUGGA 20

1156 20041

CFTR-lntronlO-

- UGGGAGAAACAGGUUU UGGA 20

1157 20042

CFTR-lntronlO-

+ U UGACCCUUUAUCAACAUGA 20

1158 20043

CFTR-lntronlO-

+ UGCUGGCAUAGCUGCACUGA 20

1159 20044

CFTR-lntronlO-

- AAAAAAUUAGCCAGACGUGA 20

1160 20045

CFTR-lntronlO-

- AAUCCUAAUUCCCAAGGUGA 20

1161 20046

CFTR-lntronlO-

- CAAAGACUUGCAGGAGGUGA 20

1162 20047

CFTR-lntronlO-

+ CACAUGGCAGAAAGGGGUGA 20

1163 20048

CFTR-lntronlO-

- AGAUUCAGGACAUGCUUUGA 20

1164 20049

CFTR-lntronlO-

+ AUAUUCAAUUCUUCAAAAUA 20

1165 20050

CFTR-lntronlO-

- AAAACU AAU UG U AG U ACAU A 20

1166 20051

CFTR-lntronlO-

- AUGCAUAGUAUUCUAUCAUA 20

1167 20052

665

5535.1 CFTR-lntronlO-

+ AAACAUAGAGAAAACUCAUA 20

1168 20053

CFTR-lntronlO-

+ UAGCUGCAGACCUCAAUAUA 20

1169 20054

CFTR-lntronlO-

+ CAAAAAUUACAGAACCUAUA 20

1170 20055

CFTR-lntronlO-

- AAAAAGUUUCUCAUCUUAUA 20

1171 20056

CFTR-lntronlO-

+ CUCCCGAGUAGCUGGGACUA 20

1172 20057

CFTR-lntronlO-

+ AAGGGGUGAGGGUCUCUCUA 20

1173 20058

CFTR-lntronlO-

+ AAGGUGUGAGGGUCUCUCUA 20

1174 20059

CFTR-lntronlO-

+ ACUGUGAAUGGUGCCAGGUA 20

1175 20060

CFTR-lntronlO-

+ AUCACUAGUGGCACUUUGUA 20

1176 20061

CFTR-lntronlO-

+ UUGAUGUUAUUCAAGGUUUA 20

1177 20062

CFTR-lntronlO-

- UAUCAUUUUGACCAUU UUUA 20

1178 20063

CFTR-lntronlO-

+ U U G G AAAAAAAAU U CAAAAC 20

1179 20064

CFTR-lntronlO-

+ CUGUGUGGCUUAUAAACAAC 20

1180 20065

CFTR-lntronlO-

+ CCAUCAUCACUUGCCUGAAC 20

1181 20066

CFTR-lntronlO-

- AGCUUUCUGGACUGAGUAAC 20

1182 20067

CFTR-lntronlO-

- UU UGUAUUUUUAGUAGAGAC 20

1183 20068

CFTR-lntronlO-

- ACAAGUGCCUAGCACUUGAC 20

1184 20069

CFTR-lntronlO-

- AAUUGACCCU U AAACAAU AC 20

1185 20070

CFTR-lntronlO-

+ UCCCAAGUAGCUGGGACUAC 20

1186 20071

CFTR-lntronlO-

+ UCCCGAGUAGCUGGGACUAC 20

1187 20072

CFTR-lntronlO-

- UCCCAAAGUGCUGGGAU UAC 20

1188 20073

666

5535.1 CFTR-lntronlO-

- UCCCAAAGUGUUGGGAUUAC 20

1189 20074

CFTR-lntronlO-

+ UACUGCAAUAUGCAAUU UAC 20

1190 20075

CFTR-lntronlO-

+ CAGGAGAAUGGCGUGAACCC 20

1191 20076

CFTR-lntronlO-

+ AGAGUCUCACUCUGUCACCC 20

1192 20077

CFTR-lntronlO-

- UAGGUCUUACUCUGUCACCC 20

1193 20078

CFTR-lntronlO-

+ CGGAAAGGUCAAUUGAGCCC 20

1194 20079

CFTR-lntronlO-

+ CAGGAGAAUUGCUUGAGCCC 20

1195 20080

CFTR-lntronlO-

- CACUGCAAGCUCCGCCUCCC 20

1196 20081

CFTR-lntronlO-

- CACUGCAACCUCUGCCUCCC 20

1197 20082

CFTR-lntronlO-

+ CCCGCCACUGCACUCCAGCC 20

1198 20083

CFTR-lntronlO-

+ CGCACCACUGUGCUCCAGCC 20

1199 20084

CFTR-lntronlO-

+ CACACCACU G AAG U U CAG CC 20

1200 20085

CFTR-lntronlO-

- CGCGCCACUGCACUCUAGCC 20

1201 20086

CFTR-lntronlO-

+ AAAAAUACAAAAAAUUAGCC 20

1202 20087

CFTR-lntronlO-

- CAGGCGCCCGCCACUACGCC 20

1203 20088

CFTR-lntronlO-

- CAGGCGUGAGCCACCGCGCC 20

1204 20089

CFTR-lntronlO-

+ UAUAAGAAAUGAAACAGGCC 20

1205 20090

CFTR-lntronlO-

- UUAGGAGAUCAAGACCAUCC 20

1206 20091

CFTR-lntronlO-

+ UCAGGAGAUCGAGACCAUCC 20

1207 20092

CFTR-lntronlO-

+ UCAAGAGAUCAAUACCAUCC 20

1208 20093

CFTR-lntronlO-

- UGAUGAUGGUGGCU UGAUCC 20

1209 20094

667

5535.1 CFTR-lntronlO-

- AGGAAGACAGCUGGCUAUCC 20

1210 20095

CFTR-lntronlO-

+ CCACGCUGGUCUCAAACUCC 20

1211 20096

CFTR-lntronlO-

- UCACUGUAACCUUGAACUCC 20

1212 20097

CFTR-lntronlO-

- UUAUUCUUU UGAUAUACUCC 20

1213 20098

CFTR-lntronlO-

- UCACUGCAAGCUCCGCCUCC 20

1214 20099

CFTR-lntronlO-

- UCACUGCAACCUCUGCCUCC 20

1215 20100

CFTR-lntronlO-

+ UCACUGCAAGUUCUGCCUCC 20

1216 20101

CFTR-lntronlO-

- CAGGUGAAUUGCUUGAGUCC 20

1217 20102

CFTR-lntronlO-

- CUGCCAUGUGAGAACACAGC 20

1218 20103

CFTR-lntronlO-

- AUCAGUGCAGCUAUGCCAGC 20

1219 20104

CFTR-lntronlO-

- AGCU U U U AAAACAAAAU AG C 20

1220 20105

CFTR-lntronlO-

- CACAAACAAAAGAAAAUAGC 20

1221 20106

CFTR-lntronlO-

+ ACCUCAGCCUCCCAAGUAGC 20

1222 20107

CFTR-lntronlO-

+ UAAAAAUACAAAAAAUUAGC 20

1223 20108

CFTR-lntronlO-

- CGGGGUUUCACCGUUU UAGC 20

1224 20109

CFTR-lntronlO-

+ AUAUAAGAAAUGAAACAGGC 20

1225 20110

CFTR-lntronlO-

- UCUCGCUCUGUCGCCCAGGC 20

1226 20111

CFTR-lntronlO-

- CAAUAAAUUUGGUGUCAGGC 20

1227 20112

CFTR-lntronlO-

+ ACACUUUGGGAGGCCGAGGC 20

1228 20113

CFTR-lntronlO-

+ UUUCUCACAGUUCUGGAGGC 20

1229 20114

CFTR-lntronlO-

- AAUUAGCCAGACGUGAUGGC 20

1230 20115

668

5535.1 CFTR-lntronlO-

- CCAGGCUGGAGUGCAGUGGC 20

1231 20116

CFTR-lntronlO-

+ AAUUAGCCGGGCGUAGUGGC 20

1232 20117

CFTR-lntronlO-

- CUUAGCAGACCCAAAUCUGC 20

1233 20118

CFTR-lntronlO-

+ UUCAUUUAUCUCGAAAUUGC 20

1234 20119

CFTR-lntronlO-

- UCCCAAGGUGAUGGUAUUGC 20

1235 20120

CFTR-lntronlO-

- ACAUUUGAACAAAGACUUGC 20

1236 20121

CFTR-lntronlO-

+ AGCCUCCACU UCUCAGGCUC 20

1237 20122

CFTR-lntronlO-

+ UAUAUAGAGAGAAACAUCUC 20

1238 20123

CFTR-lntronlO-

+ CACUGCAGCCUCCACU UCUC 20

1239 20124

CFTR-lntronlO-

+ CGGGCACCCGCCAUCACGUC 20

1240 20125

CFTR-lntronlO-

- UAGGCAUGAGCCACUGUGUC 20

1241 20126

CFTR-lntronlO-

- UGUAUGUAUAUAUGUGUGUC 20

1242 20127

CFTR-lntronlO-

+ UAUUCUUUCUAAUUUCAUUC 20

1243 20128

CFTR-lntronlO-

- AGUAGGAAGUGAUCAGAUUC 20

1244 20129

CFTR-lntronlO-

- CUUUCUUUUGAAUAUAUUUC 20

1245 20130

CFTR-lntronlO-

- AAAGAUGAUUCCAAGCUUUC 20

1246 20131

CFTR-lntronlO-

- UUCAUUAUAACACUGCUUUC 20

1247 20132

CFTR-lntronlO-

+ AAGAAAAUUUGUUUUCUUUC 20

1248 20133

CFTR-lntronlO-

+ UGUUCUCACAUGGCAGAAAG 20

1249 20134

CFTR-lntronlO-

- UU UUGAAUUUUUU UUCCAAG 20

1250 20135

CFTR-lntronlO-

+ ACCGUAAUAGCAACAGGAAG 20

1251 20136

669

5535.1 CFTR-lntronlO-

+ AGCACUUUGGGAGGCUGAAG 20

1252 20137

CFTR-lntronlO-

+ A A A A A A A A U U C AC A A A U A AG 20

1253 20138

CFTR-lntronlO-

- AUGAAAUUAGAAAGAAUAAG 20

1254 20139

CFTR-lntronlO-

- A U C A A A A A U A A A A A U A U A AG 20

1255 20140

CFTR-lntronlO-

- AUCAGUAGGCUUCCUAUAAG 20

1256 20141

CFTR-lntronlO-

+ AUAUUAAUGGCUGUGCACAG 20

1257 20142

CFTR-lntronlO-

+ UCACCUAGGCUAGGGUACAG 20

1258 20143

CFTR-lntronlO-

+ UUCUGUUUAAAACUCUCCAG 20

1259 20144

CFTR-lntronlO-

+ AG AAG G AAAG G AG G U AG CAG 20

1260 20145

CFTR-lntronlO-

+ UGCUUGAGCCCGGGAGGCAG 20

1261 20146

CFTR-lntronlO-

- CCUAGCACU UUUGGAGGCAG 20

1262 20147

CFTR-lntronlO-

+ U UUCAACAUAUGAAUGGCAG 20

1263 20148

CFTR-lntronlO-

+ UCACCCAGGCUAGAGUGCAG 20

1264 20149

CFTR-lntronlO-

- UCGCCCAGGCUGGAGUGCAG 20

1265 20150

CFTR-lntronlO-

- UGGUGUCAGGCUGGGUGCAG 20

1266 20151

CFTR-lntronlO-

- AGGAAUGUUAAUUUAUUCAG 20

1267 20152

CFTR-lntronlO-

- UCACCCAGGCUGAACUUCAG 20

1268 20153

CFTR-lntronlO-

- ACAAACAGAAAAAGAAAGAG 20

1269 20154

CFTR-lntronlO-

- AAAAAAUUAUACUAUAGGAG 20

1270 20155

CFTR-lntronlO-

+ ACUAAUAGCCUAUUGUUGAG 20

1271 20156

CFTR-lntronlO-

- CAGUAAAAAGUGAUCUCUAG 20

1272 20157

670

5535.1 CFTR-lntronlO-

+ AAAAAAUUAGCCGGGCGUAG 20

1273 20158

CFTR-lntronlO-

- AAGAAGAGAAAGGGGUGUAG 20

1274 20159

CFTR-lntronlO-

+ UUUGUUUGUGUUUUUUGUAG 20

1275 20160

CFTR-lntronlO-

- AAA U G U G AG A A A A AG U U U AG 20

1276 20161

CFTR-lntronlO-

+ CGGAGAUGAUUAGCAUCACG 20

1277 20162

CFTR-lntronlO-

- UUGUAUUUUUAGUAGAGACG 20

1278 20163

CFTR-lntronlO-

+ CCCAACACU UUGGGAGGCCG 20

1279 20164

CFTR-lntronlO-

+ CCCAGCACUUUGGGAGGCCG 20

1280 20165

CFTR-lntronlO-

- CCAGGAGUUUGAGACCAGCG 20

1281 20166

CFTR-lntronlO-

+ AG U AAAAAAAAAU CAAAAGG 20

1282 20167

CFTR-lntronlO-

+ AAACUGAGUAGAAGGAAAGG 20

1283 20168

CFTR-lntronlO-

- UGGUUUGAAGAACAGUAAGG 20

1284 20169

CFTR-lntronlO-

- UU UGAACAAAGACUUGCAGG 20

1285 20170

CFTR-lntronlO-

+ AGCACUUUGGGAGGCCGAGG 20

1286 20171

CFTR-lntronlO-

+ AAUGGCGUGAACCCGGGAGG 20

1287 20172

CFTR-lntronlO-

- AGCUACUUGGGAGGCUGAGG 20

1288 20173

CFTR-lntronlO-

- U U AAAAAAU UAUACUAUAGG 20

1289 20174

CFTR-lntronlO-

- UGAGGAAGAAAGGAAGUAGG 20

1290 20175

CFTR-lntronlO-

+ AUGAAACAGGCCGGGCGCGG 20

1291 20176

CFTR-lntronlO-

- AAGGUGAUGGUAUUGCAGGG 20

1292 20177

CFTR-lntronlO-

+ CUU UGGGAGGCCGAGGCGGG 20

1293 20178

671

5535.1 CFTR-lntronlO-

- CGUAGUCCCAGCUACUCGGG 20

1294 20179

CFTR-lntronlO-

- ACUUGGGAGGCUGAGGUGGG 20

1295 20180

CFTR-lntronlO-

+ UGUAGUCCCAGCUACUUGGG 20

1296 20181

CFTR-lntronlO-

+ UGUAAUCCCAACACUUUGGG 20

1297 20182

CFTR-lntronlO-

+ UAUAAACCCAGCACU UUGGG 20

1298 20183

CFTR-lntronlO-

+ UGUAAUCCCAGCACUUUGGG 20

1299 20184

CFTR-lntronlO-

- UGCAGGGUGGGGCCUU UGGG 20

1300 20185

CFTR-lntronlO-

- AAAUUAGCCAGACGUGAUGG 20

1301 20186

CFTR-lntronlO-

+ U UUAUUUCUCACAGUUCUGG 20

1302 20187

CFTR-lntronlO-

- CACCUGAGCCUGAGAAGUGG 20

1303 20188

CFTR-lntronlO-

- CCCAGGCUGGAGUGCAGUGG 20

1304 20189

CFTR-lntronlO-

+ AAAUUAGCCGGGCGUAGUGG 20

1305 20190

CFTR-lntronlO-

- AAGAAAAUAGCUGGGUGUGG 20

1306 20191

CFTR-lntronlO-

+ UAUUCAAAAAAUAUUUGUGG 20

1307 20192

CFTR-lntronlO-

- UGUAAUCCUAGCACUUU UGG 20

1308 20193

CFTR-lntronlO-

- AGGAAUUUUAUAUAGAAAUG 20

1309 20194

CFTR-lntronlO-

+ AUAAACAAACAAAGGAAAUG 20

1310 20195

CFTR-lntronlO-

- AAGGAAGAAAGAAGGAAAUG 20

1311 20196

CFTR-lntronlO-

- UGGGAGGUGAUUAGUCCAUG 20

1312 20197

CFTR-lntronlO-

- CCCAGCUACUCGGGAGGCUG 20

1313 20198

CFTR-lntronlO-

+ CCCAGCUACU UGGGAGGCUG 20

1314 20199

672

5535.1 CFTR-lntronlO-

+ AUACAAAAAUUAGCUGAGUG 20

1315 20200

CFTR-lntronlO-

+ UUGUGUUUU UUGUAGAGGUG 20

1316 20201

CFTR-lntronlO-

- ACAAAGACUUGCAGGAGGUG 20

1317 20202

CFTR-lntronlO-

+ CCCAGCUACUUGGGAGGGUG 20

1318 20203

CFTR-lntronlO-

+ UCACAUGGCAGAAAGGGGUG 20

1319 20204

CFTR-lntronlO-

- C A A A AG A A A A UAGCUGGGUG 20

1320 20205

CFTR-lntronlO-

+ ACAAAAUACCAUGAACUGUG 20

1321 20206

CFTR-lntronlO-

- AU U U U U AU AAAAAAU AAU UG 20

1322 20207

CFTR-lntronlO-

+ AUCUAUUCAAAAAAUAUUUG 20

1323 20208

CFTR-lntronlO-

- AAUACAUUGGAAAAUUUUUG 20

1324 20209

CFTR-lntronlO-

- UAUUAGUAGUUAAGUUUUUG 20

1325 20210

CFTR-lntronlO-

+ AUAGUAGCAAAUGAUAAAAU 20

1326 20211

CFTR-lntronlO-

+ UCUCUAUU UGGAUGUCAAAU 20

1327 20212

CFTR-lntronlO-

+ AAUAAACAAACAAAGGAAAU 20

1328 20213

CFTR-lntronlO-

- UAAGGUUUCCACUCAACAAU 20

1329 20214

CFTR-lntronlO-

+ U UUACCAUUAUCUACACAAU 20

1330 20215

CFTR-lntronlO-

- CCCCAUAAAUGUUGAAUAAU 20

1331 20216

CFTR-lntronlO-

- UU UUUUUUCAGUUAAUACAU 20

1332 20217

CFTR-lntronlO-

+ U UUUACAAUUCUUAUUACAU 20

1333 20218

CFTR-lntronlO-

- AAUACAGGCUUGAACUGCAU 20

1334 20219

CFTR-lntronlO-

- UGUACCCUAGCCUAGGUGAU 20

1335 20220

673

5535.1 CFTR-lntronlO-

+ AAAAAUAUAUAUAUGCAUAU 20

1336 20221

CFTR-lntronlO-

- CUAUUAAAAAAUUAUACUAU 20

1337 20222

CFTR-lntronlO-

- UUCUCCCUGUUAU UCCUUAU 20

1338 20223

CFTR-lntronlO-

- UAAAAAGUUUCUCAUCUUAU 20

1339 20224

CFTR-lntronlO-

- UCCCAAAGUGCUGGGUUUAU 20

1340 20225

CFTR-lntronlO-

+ UUCUCAGACU UUUAUUUUAU 20

1341 20226

CFTR-lntronlO-

+ AGUUUCCAAAUUUU UUUUAU 20

1342 20227

CFTR-lntronlO-

- UGCCCGUAGUCCCAGCUACU 20

1343 20228

CFTR-lntronlO-

+ CGCCUGUAGUCCCAGCUACU 20

1344 20229

CFTR-lntronlO-

+ UGCCUGUAGUCCCAGCUACU 20

1345 17606

CFTR-lntronlO-

+ ACCCUGCAAUACCAUCACCU 20

1346 20230

CFTR-lntronlO-

+ CCGCCACUGCACUCCAGCCU 20

1347 20231

CFTR-lntronlO-

+ ACACCACUGAAGUUCAGCCU 20

1348 20232

CFTR-lntronlO-

- ACCUCGUGAUCCGCCCGCCU 20

1349 20233

CFTR-lntronlO-

- ACCUCAUGAUCUGCCUGCCU 20

1350 20234

CFTR-lntronlO-

- CACUGUAACCU UGAACUCCU 20

1351 20235

CFTR-lntronlO-

+ CACUGCAAGUUCUGCCUCCU 20

1352 20236

CFTR-lntronlO-

- ACAAACAAAAGAAAAUAGCU 20

1353 20237

CFTR-lntronlO-

- CCUCACCCUCCCAAGUAGCU 20

1354 20238

CFTR-lntronlO-

+ CCUCAGCCUCCCAAGUAGCU 20

1355 20239

CFTR-lntronlO-

+ CCUCAGCCUCCCGAGUAGCU 20

1356 20240

674

5535.1 CFTR-lntronlO-

+ U UCUCACAGUUCUGGAGGCU 20

1357 20241

CFTR-lntronlO-

+ CCUCUGCCUCCAAAAGUGCU 20

1358 20242

CFTR-lntronlO-

- CUUCAGCCUCCCAAAGUGCU 20

1359 20243

CFTR-lntronlO-

- CCUCGGCCUCCCAAAGUGCU 20

1360 20244

CFTR-lntronlO-

- A AG A A A A A AG UUGAGUUGCU 20

1361 20245

CFTR-lntronlO-

+ AGAGUGCAGUGGCGCGAUCU 20

1362 20246

CFTR-lntronlO-

- AUCUGCUGGCACCUUGAUCU 20

1363 20247

CFTR-lntronlO-

- AAAGCUGUGCAUUUUCCUCU 20

1364 20248

CFTR-lntronlO-

+ AUAUAGAGAGAAACAUCUCU 20

1365 20249

CFTR-lntronlO-

+ AUAUUUUUCAUUAUGAUUCU 20

1366 20250

CFTR-lntronlO-

+ U UAAUUUUCUCGGUAU UUCU 20

1367 20251

CFTR-lntronlO-

+ UUACUUUUUCUUAAUUUUCU 20

1368 20252

CFTR-lntronlO-

- AAAUGAGGAAGAAAGGAAGU 20

1369 20253

CFTR-lntronlO-

- UGGAUUUUUGACUAUACAGU 20

1370 20254

CFTR-lntronlO-

- ACAUCUGCAAUUGUAUCAGU 20

1371 20255

CFTR-lntronlO-

- AU CCAAAU AG AG AUG U U AG U 20

1372 20256

CFTR-lntronlO-

- CAGG AG U U UG AG ACCAG CG U 20

1373 20257

CFTR-lntronlO-

+ UUUGUGUUU UUUGUAGAGGU 20

1374 20258

CFTR-lntronlO-

- AGGUGAUGGUAUUGCAGGGU 20

1375 20259

CFTR-lntronlO-

+ UGAAUGGUGCCAGGUAGGGU 20

1376 20260

CFTR-lntronlO-

- UUUUUGACUAUACAGUGGGU 20

1377 20261

675

5535.1 CFTR-lntronlO-

- A U A AG A AG AG A A AG G G G U G U 20

1378 20262

CFTR-lntronlO-

- AAAUUUCCACUCAAUAAAUU 20

1379 20263

CFTR-lntronlO-

+ AUACCAUCACCUUGGGAAUU 20

1380 20264

CFTR-lntronlO-

- AUGGUACUACUGUAAUAAUU 20

1381 20265

CFTR-lntronlO-

- AAUCACUAUUGAUUGACAUU 20

1382 20266

CFTR-lntronlO-

- UU UUAUUCU UUUUAGAGAUU 20

1383 20267

CFTR-lntronlO-

- CUUGCAGGAGGUGAGGGAUU 20

1384 20268

CFTR-lntronlO-

- UGAUACUUUUCUUCCUGAUU 20

1385 20269

CFTR-lntronlO-

+ AU AG AAG U AG AAG AACU AU U 20

1386 20270

CFTR-lntronlO-

- UCUUUUUCAUUGAAUGUAUU 20

1387 20271

CFTR-lntronlO-

+ UCUGUUUGUCUUAGAU UAUU 20

1388 20272

CFTR-lntronlO-

- AUUUCCUU UGUUUGUU UAUU 20

1389 20273

CFTR-lntronlO-

+ UCUCAGACUU UUAUUUUAUU 20

1390 20274

CFTR-lntronlO-

+ UGCCUGUAAUCCCAACACUU 20

1391 20275

CFTR-lntronlO-

+ UGCCUAUAAACCCAGCACUU 20

1392 20276

CFTR-lntronlO-

+ CGCCUGUAAUCCCAGCACUU 20

1393 20277

CFTR-lntronlO-

- AAGAAUUGAAUAUGAGACUU 20

1394 20278

CFTR-lntronlO-

+ CCCUGCAAUACCAUCACCUU 20

1395 20279

CFTR-lntronlO-

+ AAAAUGUUAAAUUUUCCCUU 20

1396 20280

CFTR-lntronlO-

+ AUUUUCCCUUAGGAUAUCUU 20

1397 20281

CFTR-lntronlO-

- CUU UUAGUUAGCAUAAAGUU 20

1398 20282

676

5535.1 CFTR-lntronlO-

- AGGAAGCAAGGAGAUGAGUU 20

1399 20283

CFTR-lntronlO-

- CCUCGGCCUCCCAAAGUGUU 20

1400 20284

CFTR-lntronlO-

- AGUUGUUAUCUCUGAAAUUU 20

1401 20285

CFTR-lntronlO-

- UUAUCAAUAUUUUGGAAUUU 20

1402 20286

CFTR-lntronlO-

- AUCACUAUUGAUUGACAUUU 20

1403 20287

CFTR-lntronlO-

+ AUCAAGGUGCCAGCAGAUUU 20

1404 20288

CFTR-lntronlO-

- AAAUAGUUUUAUCAAUAUUU 20

1405 20289

CFTR-lntronlO-

- CAUCAUUAUUCAUGAUAUUU 20

1406 20290

CFTR-lntronlO-

- CUUUUUCAUUGAAUGUAUUU 20

1407 20291

CFTR-lntronlO-

- ACU UGUAAUCCUAGCACUUU 20

1408 20292

CFTR-lntronlO-

- UAUUGCAGGGUGGGGCCUUU 20

1409 20293

CFTR-lntronlO-

- AAAUUUAACUGAAUAUCUUU 20

1410 20294

CFTR-lntronlO-

- U U AAU ACAU UGG AAAAU U U U 20

1411 20295

CFTR-lntronlO-

- UAUCAAUAUUUUGGAAUUUU 20

1412 20296

CFTR-lntronlO-

- U AAU ACAU UGG AAAAU U U U U 20

1413 20297

Table 41A provides exemplary targeting domains for correcting a mutation (e.g., 3272- 26->G) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within intron 10, have a high level of orthogonality, start with a 5'G, and PAM is

NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 41A

677

5535.1 1st Tier

Target Site

gRNA Name DNA Strand Targeting Domain

Length Seq ID

CFTR- IntronlO- + GAUAAUACUACUGACUAAAA 20

1414 20298

CFTR- IntronlO- + GUAACUCCAGUGCUAUUUAAA 21

1415 20299

CFTR- IntronlO- + GGUAACUCCAGUGCUAUUUAAA 22

1416 20300

CFTR- IntronlO- + GACUCCAGGAGUAUAUCAA 19

1417 20301

CFTR- IntronlO- + GGACUCCAGGAGUAUAUCAA 20

1418 20302

CFTR- IntronlO- + GUGGACUCCAGGAGUAUAUCAA 22

1419 20303

CFTR- IntronlO- + GAUGAGAGACAGUAAAGAA 19

1420 20304

CFTR- IntronlO- + GCUAUUUUUGCACAUCUAUCA 21

1421 20305

CFTR- IntronlO- + GCUACCUUGGUUGGAUGA 18

1422 20306

CFTR- IntronlO- + GGCUACCUUGGUUGGAUGA 19

1423 20307

CFTR- IntronlO- + GAUUGGCUACCUUGGUUGGAUGA 23

1424 20308

CFTR- IntronlO- + GGAUUGGCUACCUUGGUUGGAUGA 24

1425 20309

CFTR- IntronlO- + GAAUAUCCAUCCAUAUGA 18

1426 20310

678

5535.1 CFTR- IntronlO- + GUUACAACAGUCUUUAUA 18

1427 20311

CFTR- IntronlO- + GUUCAACUUAUCCAUUAAUCCUA 23

1428 20312

CFTR- IntronlO- + GAUACAAAUUACCAAAUUGUA 21

1429 20313

CFTR- IntronlO- + GCACCCAGCCUGACACCAAAUUUA 24

1430 20314

CFTR- IntronlO- + GUACAAAUAUUGACUAUUUA 20

1431 20315

CFTR- IntronlO- + GCAAGUACAAAUAUUGACUAUUUA 24

1432 20316

CFTR- IntronlO- + GAGCUCAUAUUAGUGAAC 18

1433 20317

CFTR- IntronlO- + GAUACUAAAAAAAGUUAC 18

1434 20318

CFTR- IntronlO- + GUAUUAGCAAGUGGACUCC 19

1435 20319

CFTR- IntronlO- + GCACUCUAUUUAGAGUGUAUGGC 23

1436 20320

CFTR- IntronlO- + GAAAAGGCUCUUUAUAAUGC 20

1437 20321

CFTR- IntronlO- + GCUAAGAGACUCCUGAAUC 19

1438 20322

CFTR- IntronlO- + GUCUGCUAAGAGACUCCUGAAUC 23

1439 20323

CFTR- IntronlO- + GGUCUGCUAAGAGACUCCUGAAUC 24

1440 20324

679

5535.1 CFTR- IntronlO- + G U AG AAG ACCU AAAU AU C 18

1441 20325

CFTR- IntronlO- + GAUGUAGAAGACCUAAAUAUC 21

1442 20326

CFTR- IntronlO- + GAAGAUGUAGAAGACCUAAAUAUC 24

1443 20327

CFTR- IntronlO- + GGGUCUGCUAAGAGACUC 18

1444 20328

CFTR- IntronlO- + GAUUUGGGUCUGCUAAGAGACUC 23

1445 20329

CFTR- IntronlO- + GAUAUUUUUCAUUAUGAUUC 20

1446 20330

CFTR-

+ GCUUGACAUCAGUUGGGUUC 20

lntronlO-94 18980

CFTR- IntronlO- + GAUAAAUAAUUGCCUUUC 18

1447 20331

CFTR- IntronlO- + GAUAUUGAUAAAUAAUUGCCUUUC 24

1448 20332

CFTR- IntronlO- + GUUGGAUGAGGGAAUGCAG 19

1449 20333

CFTR- IntronlO- + GGUUGGAUGAGGGAAUGCAG 20

1450 20334

CFTR- IntronlO- + GAAUUGAUCUUGAAGACAUACG 22

1451 20335

CFTR- IntronlO- + GCCUAGAUGAUUAUUAAUAGGG 22

1452 20336

CFTR- IntronlO- + GUUAAGUUGUUCUUAGGG 18

1453 20337

CFTR-

+ GGUUAAGUUGUUCUUAGGG 19

IntronlO- 20338

680

5535.1 1454

CFTR- IntronlO- + GCCAGGUUAAGUUGUUCUUAGGG 23

1455 20339

CFTR- IntronlO- + GUUACCUGGAUUGGCUACCUUGG 23

1456 20340

CFTR- IntronlO- + GGAAAUGGGGUAUAAGUG 18

1457 20341

CFTR-

+ G U U ACAU AAAAAG AG AGG UG 20

lntronlO-107 18993

CFTR- IntronlO- + GCUAAUAGCUUAUUCUAUACAU 22

1458 20342

CFTR- IntronlO- + GAGCUAAUAGCUUAUUCUAUACAU 24

1459 20343

CFTR- IntronlO- + GAAUAAUGAUGUACAUUUAAUAU 23

1460 20344

CFTR- IntronlO- + GUAAUGGAAACACUAUAUAU 20

1461 20345

CFTR- IntronlO- + GUACAUCCAACUAACAUCUCUAU 23

1462 20346

CFTR- IntronlO- + GGAAAAUGU UAAAU U U U CCCU 21

1463 20347

CFTR- IntronlO- + GCACUUGUUGACAGUCCU 18

1464 20348

CFTR- IntronlO- + GGCACUUGUUGACAGUCCU 19

1465 20349

CFTR- IntronlO- + GCUAGGCACUUGUUGACAGUCCU 23

1466 20350

CFTR-

+ GUUACUCAGUCCAGAAAGCU 20

lntronlO-117 19003

681

5535.1 CFTR- IntronlO- + GUGCAAGUCCUCUGUGCU 18

1467 20351

CFTR- IntronlO- + GCCAGGUUAAGUUGUUCU 18

1468 20352

CFTR- IntronlO- + GAGGGUCUCUCUAAGGUGU 19

1469 20353

CFTR- IntronlO- + GUGAGGGUCUCUCUAAGGUGU 21

1470 20354

CFTR- IntronlO- + GGUGAGGGUCUCUCUAAGGUGU 22

1471 20355

CFTR- IntronlO- + GGGUGAGGGUCUCUCUAAGGUGU 23

1472 20356

CFTR- IntronlO- + GGGGUGAGGGUCUCUCUAAGGUGU 24

1473 20357

CFTR- IntronlO- + GGAAAUCAGCACUCUAUU 18

1474 20358

CFTR- IntronlO- + GGGAAAUCAGCACUCUAUU 19

1475 20359

CFTR- IntronlO- + GGGGAAAUCAGCACUCUAUU 20

1476 20360

CFTR- IntronlO- + GUGGGGAAAUCAGCACUCUAUU 22

1477 20361

CFTR- IntronlO- + GUAACUCUUUAUUCACUU 18

1478 20362

CFTR- IntronlO- - GCUUUCAGGAG CCA A A A A 18

1479 20363

CFTR- IntronlO- - GAUAAGAUUCUAAAGGAAA 19

1480 20364

682

5535.1 CFTR- IntronlO- - GGAUAAGAUUCUAAAGGAAA 20

1481 20365

CFTR- IntronlO- - GCUGGAUAAGAUUCUAAAGGAAA 23

1482 20366

CFTR- IntronlO- - GGCUGGAUAAGAUUCUAAAGGAAA 24

1483 20367

CFTR- IntronlO- - GUACUCAUGCCAUACACUCUAAA 23

1484 20368

CFTR- IntronlO- - GCUUUGAAGGAAGAUCCAA 19

1485 20369

CFTR- IntronlO- - GGAGAACCAUAUUUUGAAGAA 21

1486 20370

CFTR- IntronlO- - G AGG AG AACCAU AU U U UG AAG AA 23

1487 20371

CFTR- IntronlO- - GGGUUGAUAAGAAGAGAA 18

1488 20372

CFTR-

- GAGGGUUGAUAAGAAGAGAA 20

lntronlO-68 18954

CFTR- IntronlO- - GAAAGAGGGUUGAUAAGAAGAGAA 24

1489 20373

CFTR- IntronlO- - GUACUUGCUCUCUGACCACAUAA 23

1490 20374

CFTR- IntronlO- - GUAUAUGAUAUACUCUUAA 19

1491 20375

CFTR- IntronlO- - GAUGUAUAUGAUAUACUCUUAA 22

1492 20376

CFTR- IntronlO- - GGAUGUAUAUGAUAUACUCUUAA 23

1493 20377

CFTR-

- GUAUAGAAUUUUGCAUCA 18

IntronlO- 20378

683

5535.1 1494

CFTR- IntronlO- - GGUAGUAAUUGUGUUUCA 18

1495 20379

CFTR- IntronlO- - GAAAAGGUAGUAAUUGUGUUUCA 23

1496 20380

CFTR- IntronlO- - GAUCUAGCUAAAAUAUAAGA 20

1497 20381

CFTR- IntronlO- - GAUUCCAAGCUUUCUGGA 18

1498 20382

CFTR- IntronlO- - GAUAUACUCUUAAGUGAAUA 20

1499 20383

CFTR- IntronlO- - GAUGGAUAUUCUAUGAUAUA 20

1500 20384

CFTR- IntronlO- - GGAUGGAUAUUCUAUGAUAUA 21

1501 20385

CFTR- IntronlO- - GUUUUUGCUUGCUUUUUAUA 20

1502 20386

CFTR- IntronlO- - GUCUGAGAAGACAAAGCUA 19

1503 20387

CFTR- IntronlO- - GUAAUCGGCGGUGGAGGUA 19

1504 20388

CFTR- IntronlO- - GAAGUAAUCGGCGGUGGAGGUA 22

1505 20389

CFTR- IntronlO- - GAGAAGUAAUCGGCGGUGGAGGUA 24

1506 20390

CFTR- IntronlO- - GAUCAUUGCCUCACUAUGGUA 21

1507 20391

CFTR-

- GUAAUAACUGGGACUCAUAUGUA 23

IntronlO- 20392

684

5535.1 1508

CFTR- IntronlO- - GAAGAUCCAAUAGGAUUA 18

1509 20393

CFTR- IntronlO- - GGAAGAUCCAAUAGGAUUA 19

1510 20394

CFTR- IntronlO- - GAAGGAAGAUCCAAUAGGAUUA 22

1511 20395

CFTR- IntronlO- - GCAGGAGGUGAGGGAUUA 18

1512 20396

CFTR- IntronlO- - GUUAGCAAUGGUCUAAAC 18

1513 20397

CFTR- IntronlO- - GAUUCUGUUUAAAUAGCAC 19

1514 20398

CFTR- IntronlO- - GAGAAGGUCAAACUUGAC 18

1515 20399

CFTR- IntronlO- - GUAGAGAAGGUCAAACUUGAC 21

1516 20400

CFTR- IntronlO- - GCCUUAUUCUUUUGAUAUACUCC 23

1517 20401

CFTR- IntronlO- - GUCUUGCGCUUAUGAAACUUCC 22

1518 20402

CFTR- IntronlO- - G C U U U U A A A AC A A A A U AG C 19

1519 20403

CFTR- IntronlO- - GGAAGACAGCUGGCUAUC 18

1520 20404

CFTR- IntronlO- - GCAGGAAGACAGCUGGCUAUC 21

1521 20405

CFTR-

- GCUGGCUAUCCAGGAUUC 18

IntronlO- 20406

685

5535.1 1522

CFTR- IntronlO- - GACAGCUGGCUAUCCAGGAUUC 22

1523 20407

CFTR- IntronlO- - GUUCUGUAAUUUUUGCUUC 19

1524 20408

CFTR- IntronlO- - GGUUCUGUAAUUUUUGCUUC 20

1525 20409

CFTR- IntronlO- - GACUUUGUAGUGAUCUUC 18

1526 20410

CFTR- IntronlO- - GAAGACUUUGUAGUGAUCUUC 21

1527 20411

CFTR- IntronlO- - GAGAAGACUUUGUAGUGAUCUUC 23

1528 20412

CFTR- IntronlO- - GGAGAAGACUUUGUAGUGAUCUUC 24

1529 20413

CFTR- IntronlO- - GCUUUUCAAAAUACUUUC 18

1530 20414

CFTR- IntronlO- - GAAGCUUUUCAAAAUACUUUC 21

1531 20415

CFTR- IntronlO- - GUAACAGUACAAGAAAAAAG 20

1532 20416

CFTR-

- GCAUAUGAGAAAAGUCACAG 20

lntronlO-99 18985

CFTR- IntronlO- - GGCAUAUGAGAAAAGUCACAG 21

1533 20417

CFTR- IntronlO- - GAACCCAACUGAUGUCAAGCAG 22

1534 20418

CFTR- IntronlO- - GGAACCCAACUGAUGUCAAGCAG 23

1535 20419

686

5535.1 CFTR- IntronlO- - GUAUUAGAGGUUAAGGAG 18

1536 20420

CFTR- IntronlO- - GUCUUUUCCUCUUAAUAG 18

1537 20421

CFTR- IntronlO- - GAAGUCUUUUCCUCUUAAUAG 21

1538 20422

CFTR- IntronlO- - G A A A AG CAGCUAUGAAGG 18

1539 20423

CFTR- IntronlO- - GCUUAUGAAAAGCAGCUAUGAAGG 24

1540 20424

CFTR- IntronlO- - GGCAUAGAGUAAGACAGG 18

1541 20425

CFTR- IntronlO- - GCUGGCAUAGAGUAAGACAGG 21

1542 20426

CFTR- IntronlO- - GGCUGGCAUAGAGUAAGACAGG 22

1543 20427

CFTR- IntronlO- - GAGGCUGGCAUAGAGUAAGACAGG 24

1544 20428

CFTR- IntronlO- - GGUAGUGUGAAGAUGGGG 18

1545 20429

CFTR- IntronlO- - GCUGGUAGUGUGAAGAUGGGG 21

1546 20430

CFTR- IntronlO- - GGCUGGUAGUGUGAAGAUGGGG 22

1547 20431

CFTR- IntronlO- - GGGCUGGUAGUGUGAAGAUGGGG 23

1548 20432

CFTR- IntronlO- - GGGGCUGGUAGUGUGAAGAUGGGG 24

1549 20433

687

5535.1 CFTR- IntronlO- - GGGAAUGCAGACUCUGGG 18

1550 20434

CFTR- IntronlO- - GAUUAGGGAAUGCAGACUCUGGG 23

1551 20435

CFTR- IntronlO- - GGAUUAGGGAAUGCAGACUCUGGG 24

1552 20436

CFTR- IntronlO- - GGGGGAGCCCCAUAAAUG 18

1553 20437

CFTR- IntronlO- - GUGGGGGAGCCCCAUAAAUG 20

1554 20438

CFTR- IntronlO- - GUGAGAUUAGAGGCCACUG 19

1555 20439

CFTR- IntronlO- - GGUGAGAUUAGAGGCCACUG 20

1556 20440

CFTR- IntronlO- - GCACAUAUGUUCAGACUG 18

1557 20441

CFTR- IntronlO- - GACUUGCACAUAUGUUCAGACUG 23

1558 20442

CFTR- IntronlO- - GGACUUGCACAUAUGUUCAGACUG 24

1559 20443

CFTR- IntronlO- - GCAUCUCACCAGUGUGUG 18

1560 20444

CFTR- IntronlO- - GGCAUCUCACCAGUGUGUG 19

1561 20445

CFTR- IntronlO- - GAGGAGAACCAUAUUUUG 18

1562 20446

CFTR- IntronlO- - GAUGAGGAGAACCAUAUUUUG 21

1563 20447

688

5535.1 CFTR- IntronlO- - GCCCCAUAAAUGUUGAAUAAU 21

1564 20448

CFTR- IntronlO- - GAGCCCCAUAAAUGUUGAAUAAU 23

1565 20449

CFTR- IntronlO- - GGAGCCCCAUAAAUGUUGAAUAAU 24

1566 20450

CFTR- IntronlO- - GAUUUUUUCCCAUGUAAU 18

1567 20451

CFTR- IntronlO- - GAAUCACUAUUGAUUGACAU 20

1568 20452

CFTR- IntronlO- - GUAGUUUCUAUUAAUAGAU 19

1569 20453

CFTR- IntronlO- - GUGUAGUUUCUAUUAAUAGAU 21

1570 20454

CFTR- IntronlO- - GAAAGAGCUUUCUAGUAU 18

1571 20455

CFTR- IntronlO- - GAGAAAGAGCUUUCUAGUAU 20

1572 20456

CFTR- IntronlO- - GUUCAAAUUAUUUCUACUGCU 21

1573 20457

CFTR- IntronlO- - GUUGUUCAAAUUAUUUCUACUGCU 24

1574 20458

CFTR- IntronlO- - GUAAAGACUAAGGCUUAUUUCU 22

1575 20459

CFTR- IntronlO- - GAUAAGAAGAGAAAGGGGUGU 21

1576 20460

CFTR- IntronlO- - GUUGAUAAGAAGAGAAAGGGGUGU 24

1577 20461

689

5535.1 CFTR- IntronlO- - GUUGUUAUCUCUGAAAUU 18

1578 20462

CFTR- IntronlO- - GCUAUUACGGUAAGCUCAAGCAUU 24

1579 20463

CFTR- IntronlO- - GCUGCCUUUUAGUAGUAUU 19

1580 20464

CFTR-

- GGCUGCCUUUUAGUAGUAUU 20

lntronlO-126 19012

CFTR- IntronlO- - GAGGCUGCCUUUUAGUAGUAUU 22

1581 20465

CFTR- IntronlO- - GGAGGCUGCCUUUUAGUAGUAUU 23

1582 20466

CFTR- IntronlO- - GAAUAGAUUAGCUUAUAUACUU 22

1583 20467

CFTR- IntronlO- - GUUAGAGGAAGGCAGUGGUCCCUU 24

1584 20468

CFTR- IntronlO- - GAUGUGCAAAAAUAGCUU 18

1585 20469

CFTR- IntronlO- - GAUAGAUGUGCAAAAAUAGCUU 22

1586 20470

CFTR- IntronlO- - GUUACAUGACCUUCCUUUCUU 21

1587 20471

CFTR- IntronlO- - GAUAAUGGGAGAAACAGGUU 20

1588 20472

CFTR- IntronlO- - GCACUGGAGUUACCUGUU 18

1589 20473

CFTR- IntronlO- - GCAAAU AG UUUUAUCAAUAUUU 22

1590 20474

CFTR-

- GUUUUGGAUGGAGCUUGGUUU 21

IntronlO- 20475

690

5535.1 1591

CFTR- IntronlO- - GGUUUUGGAUGGAGCUUGGUUU 22

1592 20476

CFTR- IntronlO- - GUCCUCCACAAAUAUUUU 18

1593 20477

Table 41B provides exemplary targeting domains for correcting a mutation (e.g., 3272- 26->G) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within intron 10, have a high level of orthogonality and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 41B

691

5535.1 1600

CFTR- IntronlO- + UAACUCCAGUGCUAUUUAAA 20

1601 20485

CFTR- IntronlO- + AGGUAACUCCAGUGCUAUUUAAA 23

1602 20486

CFTR- IntronlO- + CAGGUAACUCCAGUGCUAUUUAAA 24

1603 20487

CFTR- IntronlO- + ACUCCAGGAGUAUAUCAA 18

1604 20488

CFTR- IntronlO- + UGGACUCCAGGAGUAUAUCAA 21

1605 20489

CFTR- IntronlO- + AGUGGACUCCAGGAGUAUAUCAA 23

1606 20490

CFTR- IntronlO- + AAGUGGACUCCAGGAGUAUAUCAA 24

1607 20491

CFTR- IntronlO- + AUGAGAGACAGUAAAGAA 18

1608 20492

CFTR- IntronlO- + AGAUGAGAGACAGUAAAGAA 20

1104 19989

CFTR- IntronlO- + AGGGUGGGAUAUGGAGAA 18

1609 20493

CFTR- IntronlO- + UAGGGUGGGAUAUGGAGAA 19

1610 20494

CFTR- IntronlO- + UUAGGGUGGGAUAUGGAGAA 20

1611 20495

CFTR- IntronlO- + UUUACCAUUAUCUACACA 18

1612 20496

CFTR-

+ UUUUACCAUUAUCUACACA 19

IntronlO- 20497

692

5535.1 1613

CFTR- IntronlO- + UUUUUACCAUUAUCUACACA 20

1614 20498

CFTR- IntronlO- + UAGUGAACUAGAGUCACA 18

1615 20499

CFTR- IntronlO- + UUAGUGAACUAGAGUCACA 19

1616 20500

CFTR- IntronlO- + AUUAGUGAACUAGAGUCACA 20

1617 20501

CFTR- IntronlO- + UAUUAGUGAACUAGAGUCACA 21

1618 20502

CFTR- IntronlO- + AUAUUAGUGAACUAGAGUCACA 22

1619 20503

CFTR- IntronlO- + CAUAUUAGUGAACUAGAGUCACA 23

1620 20504

CFTR- IntronlO- + UCAUAUUAGUGAACUAGAGUCACA 24

1621 20505

CFTR- IntronlO- + UGGAGAAGAGGAUGACCA 18

1622 20506

CFTR- IntronlO- + AUGGAGAAGAGGAUGACCA 19

1623 20507

CFTR- IntronlO- + UAUGGAGAAGAGGAUGACCA 20

1624 20508

CFTR- IntronlO- + AGAGACACACCUAAAGCA 18

1625 20509

CFTR- IntronlO- + AAGAGACACACCUAAAGCA 19

1626 20510

CFTR-

+ AAAGAGACACACCUAAAGCA 20

IntronlO- 20511

693

5535.1 1627

CFTR- IntronlO- + UAGUGAUUCAUUAUAUCA 18

1628 20512

CFTR- IntronlO- + AUAGUGAUUCAUUAUAUCA 19

1629 20513

CFTR- IntronlO- + AAUAGUGAUUCAUUAUAUCA 20

1630 20514

CFTR- IntronlO- + AUUUUUGCACAUCUAUCA 18

1631 20515

CFTR- IntronlO- + UAUUUUUGCACAUCUAUCA 19

1632 20516

CFTR- IntronlO- + CUAUUUUUGCACAUCUAUCA 20

1633 20517

CFTR- IntronlO- + AGCUAUUUUUGCACAUCUAUCA 22

1634 20518

CFTR- IntronlO- + AAGCUAUUUUUGCACAUCUAUCA 23

1635 20519

CFTR- IntronlO- + AAAGCUAUUUUUGCACAUCUAUCA 24

1636 20520

CFTR- IntronlO- + AAAAGGCAGCCUCCUAGA 18

1637 20521

CFTR- IntronlO- + UAAAAGGCAGCCUCCUAGA 19

1638 20522

CFTR- IntronlO- + CUAAAAGGCAGCCUCCUAGA 20

1639 20523

CFTR-

+ UGGCUACCUUGGUUGGAUGA 20

lntronlO-375 19261

CFTR- IntronlO- + UUGGCUACCUUGGUUGGAUGA 21

1640 20524

694

5535.1 CFTR- IntronlO- + AUUGGCUACCUUGGUUGGAUGA 22

1641 20525

CFTR- IntronlO- + AGAAUAUCCAUCCAUAUGA 19

1642 20526

CFTR- IntronlO- + UAGAAUAUCCAUCCAUAUGA 20

1643 20527

CFTR- IntronlO- + AUAGAAUAUCCAUCCAUAUGA 21

1644 20528

CFTR- IntronlO- + CAUAGAAUAUCCAUCCAUAUGA 22

1645 20529

CFTR- IntronlO- + UCAUAGAAUAUCCAUCCAUAUGA 23

1646 20530

CFTR- IntronlO- + AUCAUAGAAUAUCCAUCCAUAUGA 24

1647 20531

CFTR- IntronlO- + AUUACCAAAUUGUAUUGA 18

1648 20532

CFTR- IntronlO- + AAUUACCAAAUUGUAUUGA 19

1649 20533

CFTR- IntronlO- + AAAUUACCAAAUUGUAUUGA 20

1650 20534

CFTR- IntronlO- + AAAAUUACAGAACCUAUA 18

1651 20535

CFTR- IntronlO- + AAAAAU U ACAG AACCU AU A 19

1652 20536

CFTR- IntronlO- + CAAAAAUUACAGAACCUAUA 20

1170 20055

CFTR- IntronlO- + UGUUACAACAGUCUUUAUA 19

1653 20537

695

5535.1 CFTR- IntronlO- + UUGUUACAACAGUCUUUAUA 20

1654 20538

CFTR- IntronlO- + UCCUCCCUUGUCUCCCUA 18

1655 20539

CFTR- IntronlO- + UUCCUCCCUUGUCUCCCUA 19

1656 20540

CFTR- IntronlO- + CUUCCUCCCUUGUCUCCCUA 20

1657 20541

CFTR- IntronlO- + ACUUAUCCAUUAAUCCUA 18

1658 20542

CFTR- IntronlO- + AACUUAUCCAUUAAUCCUA 19

1659 20543

CFTR- IntronlO- + CAACUUAUCCAUUAAUCCUA 20

1660 20544

CFTR- IntronlO- + UCAACUUAUCCAUUAAUCCUA 21

1661 20545

CFTR- IntronlO- + UUCAACUUAUCCAUUAAUCCUA 22

1662 20546

CFTR- IntronlO- + UGUUCAACUUAUCCAUUAAUCCUA 24

1663 20547

CFTR- IntronlO- + ACAAAU U ACCAAAU UG U A 18

1664 20548

CFTR- IntronlO- + U ACAAAU U ACCAAAU UGU A 19

1665 20549

CFTR- IntronlO- + AU ACAAAU U ACCAAAU UG U A 20

1666 20550

CFTR- IntronlO- + U GAU ACAAAU U ACCAAAU UG U A 22

1667 20551

696

5535.1 CFTR- IntronlO- + CUGAUACAAAUUACCAAAUUGUA 23

1668 20552

CFTR- IntronlO- + UCUGAUACAAAUUACCAAAUUGUA 24

1669 20553

CFTR- IntronlO- + AGCCUGACACCAAAUUUA 18

1670 20554

CFTR- IntronlO- + CAGCCUGACACCAAAUUUA 19

1671 20555

CFTR- IntronlO- + CCAGCCUGACACCAAAUUUA 20

1672 20556

CFTR- IntronlO- + CCCAGCCUGACACCAAAUUUA 21

1673 20557

CFTR- IntronlO- + ACCCAGCCUGACACCAAAUUUA 22

1674 20558

CFTR- IntronlO- + CACCCAG CCUG ACACCAAAU U U A 23

1675 20559

CFTR- IntronlO- + ACAAAUAUUGACUAUUUA 18

1676 20560

CFTR- IntronlO- + UACAAAUAUUGACUAUUUA 19

1677 20561

CFTR- IntronlO- + AGUACAAAUAUUGACUAUUUA 21

1678 20562

CFTR- IntronlO- + AAGUACAAAUAUUGACUAUUUA 22

1679 20563

CFTR- IntronlO- + CAAGUACAAAUAUUGACUAUUUA 23

1680 20564

CFTR- IntronlO- + AGAGCUCAUAUUAGUGAAC 19

1681 20565

697

5535.1 CFTR- IntronlO- + CAGAGCUCAUAUUAGUGAAC 20

1682 20566

CFTR- IntronlO- + UCAGAGCUCAUAUUAGUGAAC 21

1683 20567

CFTR- IntronlO- + AUCAGAGCUCAUAUUAGUGAAC 22

1684 20568

CFTR- IntronlO- + UAUCAGAGCUCAUAUUAGUGAAC 23

1685 20569

CFTR- IntronlO- + UUAUCAGAGCUCAUAUUAGUGAAC 24

1686 20570

CFTR- IntronlO- + UCUAUUAAUAGAAACUAC 18

1687 20571

CFTR- IntronlO- + AUCUAUUAAUAGAAACUAC 19

1688 20572

CFTR- IntronlO- + AAUCUAUUAAUAGAAACUAC 20

1689 20573

CFTR- IntronlO- + UAAUCUAUUAAUAGAAACUAC 21

1690 20574

CFTR- IntronlO- + CUAAUCUAUUAAUAGAAACUAC 22

1691 20575

CFTR- IntronlO- + UCUAAUCUAUUAAUAGAAACUAC 23

1692 20576

CFTR- IntronlO- + CUCUAAUCUAUUAAUAGAAACUAC 24

1693 20577

CFTR- IntronlO- + UACUACUUCCACUACUAC 18

1694 20578

CFTR- IntronlO- + AUACUACUUCCACUACUAC 19

1695 20579

698

5535.1 CFTR- IntronlO- + UAUACUACUUCCACUACUAC 20

1696 20580

CFTR- IntronlO- + CUAUACUACUUCCACUACUAC 21

1697 20581

CFTR- IntronlO- + ACUAUACUACUUCCACUACUAC 22

1698 20582

CFTR- IntronlO- + UACUAUACUACUUCCACUACUAC 23

1699 20583

CFTR- IntronlO- + CUACUAUACUACUUCCACUACUAC 24

1700 20584

CFTR- IntronlO- + AUGAGUCCCAGUUAUUAC 18

1701 20585

CFTR- IntronlO- + UAUGAGUCCCAGUUAUUAC 19

1702 20586

CFTR- IntronlO- + AUAUGAGUCCCAGUUAUUAC 20

1703 20587

CFTR- IntronlO- + CAUAUGAGUCCCAGUUAUUAC 21

1704 20588

CFTR- IntronlO- + ACAUAUGAGUCCCAGUUAUUAC 22

1705 20589

CFTR- IntronlO- + UACAUAUGAGUCCCAGUUAUUAC 23

1706 20590

CFTR- IntronlO- + AUACAUAUGAGUCCCAGUUAUUAC 24

1707 20591

CFTR- IntronlO- + AGAUACUAAAAAAAGUUAC 19

1708 20592

CFTR- IntronlO- + A AG A U AC U A A A A A A AG U U AC 20

1709 20593

699

5535.1 CFTR- IntronlO- + UAUUAGCAAGUGGACUCC 18

1710 20594

CFTR-

+ UGUAUUAGCAAGUGGACUCC 20

lntronlO-426 19312

CFTR- IntronlO- + UUGUAUUAGCAAGUGGACUCC 21

1711 20595

CFTR- IntronlO- + AUUGUAUUAGCAAGUGGACUCC 22

1712 20596

CFTR- IntronlO- + AAUUGUAUUAGCAAGUGGACUCC 23

1713 20597

CFTR- IntronlO- + CAAUUGUAUUAGCAAGUGGACUCC 24

1714 20598

CFTR- IntronlO- + UGAGCCUAUCACCUAGGC 18

1715 20599

CFTR- IntronlO- + UUGAGCCUAUCACCUAGGC 19

1716 20600

CFTR- IntronlO- + UUUGAGCCUAUCACCUAGGC 20

1717 20601

CFTR- IntronlO- + CUAUUUAGAGUGUAUGGC 18

1718 20602

CFTR- IntronlO- + UCUAUUUAGAGUGUAUGGC 19

1719 20603

CFTR- IntronlO- + CUCUAUUUAGAGUGUAUGGC 20

1720 20604

CFTR- IntronlO- + ACUCUAUUUAGAGUGUAUGGC 21

1721 20605

CFTR- IntronlO- + CACUCUAUUUAGAGUGUAUGGC 22

1722 20606

CFTR-

+ AGCACUCUAUUUAGAGUGUAUGGC 24

IntronlO- 20607

700

5535.1 1723

CFTR- IntronlO- + AAAGGCUCUUUAUAAUGC 18

1724 20608

CFTR- IntronlO- + AAAAGGCUCUUUAUAAUGC 19

1725 20609

CFTR- IntronlO- + AGAAAAGGCUCUUUAUAAUGC 21

1726 20610

CFTR- IntronlO- + AAGAAAAGGCUCUUUAUAAUGC 22

1727 20611

CFTR- IntronlO- + AAAGAAAAGGCUCUUUAUAAUGC 23

1728 20612

CFTR- IntronlO- + AAAAGAAAAGGCUCUUUAUAAUGC 24

1729 20613

CFTR- IntronlO- + CUAAGAGACUCCUGAAUC 18

1730 20614

CFTR- IntronlO- + UGCUAAGAGACUCCUGAAUC 20

1731 20615

CFTR- IntronlO- + CUGCUAAGAGACUCCUGAAUC 21

1732 20616

CFTR- IntronlO- + UCUGCUAAGAGACUCCUGAAUC 22

1733 20617

CFTR- IntronlO- + UGUAGAAGACCUAAAUAUC 19

1734 20618

CFTR- IntronlO- + AUGUAGAAGACCUAAAUAUC 20

1735 20619

CFTR- IntronlO- + AGAUGUAGAAGACCUAAAUAUC 22

1736 20620

CFTR-

+ AAGAUGUAGAAGACCUAAAUAUC 23

IntronlO- 20621

701

5535.1 1737

CFTR- IntronlO- + UGGGUCUGCUAAGAGACUC 19

1738 20622

CFTR- IntronlO- + UUGGGUCUGCUAAGAGACUC 20

1739 20623

CFTR- IntronlO- + UUUGGGUCUGCUAAGAGACUC 21

1740 20624

CFTR- IntronlO- + AUUUGGGUCUGCUAAGAGACUC 22

1741 20625

CFTR- IntronlO- + AGAUUUGGGUCUGCUAAGAGACUC 24

1742 20626

CFTR- IntronlO- + UACUAUUGCUUUCAUUAAGUC 21

1743 20627

CFTR- IntronlO- + CUACUAUUGCUUUCAUUAAGUC 22

1744 20628

CFTR- IntronlO- + UCUACUAUUGCUUUCAUUAAGUC 23

1745 20629

CFTR- IntronlO- + CUCUACUAUUGCUUUCAUUAAGUC 24

1746 20630

CFTR- IntronlO- + UAGAGACAAGGUGGUGUC 18

1747 20631

CFTR- IntronlO- + AUAGAGACAAGGUGGUGUC 19

1748 20632

CFTR-

+ AAUAGAGACAAGGUGGUGUC 20

lntronlO-437 19323

CFTR- IntronlO- + UAAUAGAGACAAGGUGGUGUC 21

1749 20633

CFTR- IntronlO- + AUAAUAGAGACAAGGUGGUGUC 22

1750 20634

702

5535.1 CFTR- IntronlO- + AAUAAUAGAGACAAGGUGGUGUC 23

1751 20635

CFTR- IntronlO- + CAAUAAUAGAGACAAGGUGGUGUC 24

1752 20636

CFTR- IntronlO- + UAUUUUUCAUUAUGAUUC 18

1753 20637

CFTR- IntronlO- + AUAUUUUUCAUUAUGAUUC 19

1754 20638

CFTR- IntronlO- + UUGACAUCAGUUGGGUUC 18

1755 20639

CFTR- IntronlO- + CUUGACAUCAGUUGGGUUC 19

1756 20640

CFTR- IntronlO- + UGCUUGACAUCAGUUGGGUUC 21

1757 20641

CFTR- IntronlO- + CUGCUUGACAUCAGUUGGGUUC 22

1758 20642

CFTR- IntronlO- + UCUGCUUGACAUCAGUUGGGUUC 23

1759 20643

CFTR- IntronlO- + UUCUGCUUGACAUCAGUUGGGUUC 24

1760 20644

CFTR- IntronlO- + UGAUAAAUAAUUGCCUUUC 19

1761 20645

CFTR-

+ UUGAUAAAUAAUUGCCUUUC 20

Intron 10-445 19331

CFTR- IntronlO- + AUUGAUAAAUAAUUGCCUUUC 21

1762 20646

CFTR- IntronlO- + UAUUGAUAAAUAAUUGCCUUUC 22

1763 20647

CFTR-

+ AUAUUGAUAAAUAAUUGCCUUUC 23

IntronlO- 20648

703

5535.1 1764

CFTR- IntronlO- + UUGGAUGAGGGAAUGCAG 18

1765 20649

CFTR- IntronlO- + UGGUUGGAUGAGGGAAUGCAG 21

1766 20650

CFTR- IntronlO- + UUGGUUGGAUGAGGGAAUGCAG 22

1767 20651

CFTR- IntronlO- + CUUGGUUGGAUGAGGGAAUGCAG 23

1768 20652

CFTR- IntronlO- + CCUUGGUUGGAUGAGGGAAUGCAG 24

1769 20653

CFTR- IntronlO- + CCUUCUGCUUGACAUCAG 18

1770 20654

CFTR- IntronlO- + CCCUUCUGCUUGACAUCAG 19

1771 20655

CFTR- IntronlO- + ACCCUUCUGCUUGACAUCAG 20

1772 20656

CFTR- IntronlO- + CACCCUUCUGCUUGACAUCAG 21

1773 20657

CFTR- IntronlO- + ACACCCUUCUGCUUGACAUCAG 22

1774 20658

CFTR- IntronlO- + AACACCCUUCUGCUUGACAUCAG 23

1775 20659

CFTR- IntronlO- + UAACACCCUUCUGCUUGACAUCAG 24

1776 20660

CFTR- IntronlO- + AAUUGAUCUUGAAGACAUACG 21

1777 20661

CFTR-

+ AGAAUUGAUCUUGAAGACAUACG 23

IntronlO- 20662

704

5535.1 1778

CFTR- IntronlO- + UAGAAUUGAUCUUGAAGACAUACG 24

1779 20663

CFTR- IntronlO- + ACUGUGAAUGGUGCCAGG 18

1780 20664

CFTR- IntronlO- + UACUGUGAAUGGUGCCAGG 19

1781 20665

CFTR- IntronlO- + UUACUGUGAAUGGUGCCAGG 20

1782 20666

CFTR- IntronlO- + UUUACUGUGAAUGGUGCCAGG 21

1783 20667

CFTR- IntronlO- + CUUUACUGUGAAUGGUGCCAGG 22

1784 20668

CFTR- IntronlO- + UCUUUACUGUGAAUGGUGCCAGG 23

1785 20669

CFTR- IntronlO- + CUCUUUACUGUGAAUGGUGCCAGG 24

1786 20670

CFTR- IntronlO- + AGAUGAUUAUUAAUAGGG 18

1787 20671

CFTR- IntronlO- + UAGAUGAUUAUUAAUAGGG 19

1788 20672

CFTR- IntronlO- + CUAGAUGAUUAUUAAUAGGG 20

1789 20673

CFTR- IntronlO- + CCUAGAUGAUUAUUAAUAGGG 21

1790 20674

CFTR- IntronlO- + AGCCUAGAUGAUUAUUAAUAGGG 23

1791 20675

CFTR-

+ CAGCCUAGAUGAUUAUUAAUAGGG 24

IntronlO- 20676

705

5535.1 1792

CFTR-

+ AGGUUAAGUUGUUCUUAGGG 20

lntronlO-475 19361

CFTR- IntronlO- + CAGGUUAAGUUGUUCUUAGGG 21

1793 20677

CFTR- IntronlO- + CCAGGUUAAGUUGUUCUUAGGG 22

1794 20678

CFTR- IntronlO- + UGCCAGGUUAAGUUGUUCUUAGGG 24

1795 20679

CFTR- IntronlO- + UAACAAACCUUUUAUUGG 18

1796 20680

CFTR- IntronlO- + U U AACAAACCU UUUAUUGG 19

1797 20681

CFTR- IntronlO- + U U U AACAAACCU UUUAUUGG 20

1798 20682

CFTR- IntronlO- + CUGGAUUGGCUACCUUGG 18

1799 20683

CFTR- IntronlO- + CCUGGAUUGGCUACCUUGG 19

1800 20684

CFTR- IntronlO- + ACCUGGAUUGGCUACCUUGG 20

1801 20685

CFTR- IntronlO- + UACCUGGAUUGGCUACCUUGG 21

1802 20686

CFTR- IntronlO- + UUACCUGGAUUGGCUACCUUGG 22

1803 20687

CFTR- IntronlO- + AGUUACCUGGAUUGGCUACCUUGG 24

1804 20688

CFTR- IntronlO- + AGGAAAUGGGGUAUAAGUG 19

1805 20689

706

5535.1 CFTR-

+ AAGGAAAUGGGGUAUAAGUG 20

Intron 10-487 19373

CFTR- IntronlO- + UACAUAAAAAGAGAGGUG 18

1806 20690

CFTR- IntronlO- + UUACAUAAAAAGAGAGGUG 19

1807 20691

CFTR- IntronlO- + UGUUACAUAAAAAGAGAGGUG 21

1808 20692

CFTR- IntronlO- + UUGUUACAUAAAAAGAGAGGUG 22

1809 20693

CFTR- IntronlO- + AUUGUUACAUAAAAAGAGAGGUG 23

1810 20694

CFTR- IntronlO- + UAUUGUUACAUAAAAAGAGAGGUG 24

1811 20695

CFTR- IntronlO- + ACAGUUUCAUCUUACUUG 18

1812 20696

CFTR- IntronlO- + AACAGUUUCAUCUUACUUG 19

1813 20697

CFTR- IntronlO- + UAACAGUUUCAUCUUACUUG 20

1814 20698

CFTR- IntronlO- + AUAACAGUUUCAUCUUACUUG 21

1815 20699

CFTR- IntronlO- + UAUAACAGUUUCAUCUUACUUG 22

1816 20700

CFTR- IntronlO- + UUAUAACAGUUUCAUCUUACUUG 23

1817 20701

CFTR- IntronlO- + AUUAUAACAGUUUCAUCUUACUUG 24

1818 20702

CFTR-

+ UAUUACAUGGGAAAAAAU 18

IntronlO- 20703

707

5535.1 1819

CFTR- IntronlO- + UUAUUACAUGGGAAAAAAU 19

1820 20704

CFTR- IntronlO- + CUUAUUACAUGGGAAAAAAU 20

1821 20705

CFTR- IntronlO- + UCUUAUUACAUGGGAAAAAAU 21

1822 20706

CFTR- IntronlO- + UUCUUAUUACAUGGGAAAAAAU 22

1823 20707

CFTR- IntronlO- + AUUCUUAUUACAUGGGAAAAAAU 23

1824 20708

CFTR- IntronlO- + AAUUCUUAUUACAUGGGAAAAAAU 24

1825 20709

CFTR- IntronlO- + AUAGCUUAUUCUAUACAU 18

1826 20710

CFTR- IntronlO- + AAUAGCUUAUUCUAUACAU 19

1827 20711

CFTR- IntronlO- + UAAUAGCUUAUUCUAUACAU 20

1828 20712

CFTR- IntronlO- + CUAAUAGCUUAUUCUAUACAU 21

1829 20713

CFTR- IntronlO- + AGCUAAUAGCUUAUUCUAUACAU 23

1830 20714

CFTR- IntronlO- + AUGAUGUACAUUUAAUAU 18

1831 20715

CFTR- IntronlO- + AAUGAUGUACAUUUAAUAU 19

1832 20716

CFTR-

+ UAAUGAUGUACAUUUAAUAU 20

IntronlO- 20717

708

5535.1 1833

CFTR- IntronlO- + AUAAUGAUGUACAUUUAAUAU 21

1834 20718

CFTR- IntronlO- + AAUAAUGAUGUACAUUUAAUAU 22

1835 20719

CFTR- IntronlO- + UGAAUAAUGAUGUACAUUUAAUAU 24

1836 20720

CFTR- IntronlO- + AGAUCUCUGCAAACAUAU 18

1837 20721

CFTR- IntronlO- + AAGAUCUCUGCAAACAUAU 19

1838 20722

CFTR- IntronlO- + UAAGAUCUCUGCAAACAUAU 20

1839 20723

CFTR- IntronlO- + AUAAGAUCUCUGCAAACAUAU 21

1840 20724

CFTR- IntronlO- + CAUAAGAUCUCUGCAAACAUAU 22

1841 20725

CFTR- IntronlO- + ACAUAAGAUCUCUGCAAACAUAU 23

1842 20726

CFTR- IntronlO- + UACAUAAGAUCUCUGCAAACAUAU 24

1843 20727

CFTR- IntronlO- + AAUGGAAACACUAUAUAU 18

1844 20728

CFTR- IntronlO- + UAAUGGAAACACUAUAUAU 19

1845 20729

CFTR- IntronlO- + UGUAAUGGAAACACUAUAUAU 21

1846 20730

CFTR-

+ AUGUAAUGGAAACACUAUAUAU 22

IntronlO- 20731

709

5535.1 1847

CFTR- IntronlO- + AAUGUAAUGGAAACACUAUAUAU 23

1848 20732

CFTR- IntronlO- + CAAUGUAAUGGAAACACUAUAUAU 24

1849 20733

CFTR- IntronlO- + UCCAACUAACAUCUCUAU 18

1850 20734

CFTR- IntronlO- + AUCCAACUAACAUCUCUAU 19

1851 20735

CFTR- IntronlO- + CAUCCAACUAACAUCUCUAU 20

1852 20736

CFTR- IntronlO- + ACAU CCAACU AACAU CU CU AU 21

1853 20737

CFTR- IntronlO- + UACAUCCAACUAACAUCUCUAU 22

1854 20738

CFTR- IntronlO- + UGUACAUCCAACUAACAUCUCUAU 24

1855 20739

CFTR- IntronlO- + UCCUUAACCUCUAAUACU 18

1856 20740

CFTR- IntronlO- + CUCCUUAACCUCUAAUACU 19

1857 20741

CFTR- IntronlO- + CCUCCUUAACCUCUAAUACU 20

1858 20742

CFTR- IntronlO- + ACCUCCUUAACCUCUAAUACU 21

1859 20743

CFTR- IntronlO- + CACCUCCUUAACCUCUAAUACU 22

1860 20744

CFTR-

+ CCACCUCCUUAACCUCUAAUACU 23

IntronlO- 20745

710

5535.1 1861

CFTR- IntronlO- + CCCACCUCCUUAACCUCUAAUACU 24

1862 20746

CFTR- IntronlO- + UGGAAAAUGUUAAAUUUUCCCU 22

1863 20747

CFTR- IntronlO- + CUGGAAAAUGUUAAAUUUUCCCU 23

1864 20748

CFTR- IntronlO- + UCUGGAAAAUGUUAAAUUUUCCCU 24

1865 20749

CFTR-

+ AGGCACUUGUUGACAGUCCU 20

lntronlO-516 19402

CFTR- IntronlO- + UAGGCACUUGUUGACAGUCCU 21

1866 20750

CFTR- IntronlO- + CUAGGCACUUGUUGACAGUCCU 22

1867 20751

CFTR- IntronlO- + UGCUAGGCACUUGUUGACAGUCCU 24

1868 20752

CFTR- IntronlO- + UACUCAGUCCAGAAAGCU 18

1869 20753

CFTR- IntronlO- + UUACUCAGUCCAGAAAGCU 19

1870 20754

CFTR- IntronlO- + UGUGCAAGUCCUCUGUGCU 19

1871 20755

CFTR- IntronlO- + AUGUGCAAGUCCUCUGUGCU 20

1872 20756

CFTR- IntronlO- + UAUGUGCAAGUCCUCUGUGCU 21

1873 20757

CFTR- IntronlO- + AUAUGUGCAAGUCCUCUGUGCU 22

1874 20758

711

5535.1 CFTR- IntronlO- + CAUAUGUGCAAGUCCUCUGUGCU 23

1875 20759

CFTR- IntronlO- + ACAUAUGUGCAAGUCCUCUGUGCU 24

1876 20760

CFTR- IntronlO- + UUAAUUGCCAGUAAGUCU 18

1877 20761

CFTR- IntronlO- + UUUAAUUGCCAGUAAGUCU 19

1878 20762

CFTR-

+ AUUUAAUUGCCAGUAAGUCU 20

lntronlO-526 19412

CFTR- IntronlO- + UGCCAGGUUAAGUUGUUCU 19

1879 20763

CFTR- IntronlO- + AUGCCAGGUUAAGUUGUUCU 20

1880 20764

CFTR- IntronlO- + AGAGUGUAUGGCAUGAGU 18

1881 20765

CFTR- IntronlO- + UAGAGUGUAUGGCAUGAGU 19

1882 20766

CFTR- IntronlO- + UUAGAGUGUAUGGCAUGAGU 20

1883 20767

CFTR- IntronlO- + UUUAGAGUGUAUGGCAUGAGU 21

1884 20768

CFTR- IntronlO- + AUUUAGAGUGUAUGGCAUGAGU 22

1885 20769

CFTR- IntronlO- + UAUUUAGAGUGUAUGGCAUGAGU 23

1886 20770

CFTR- IntronlO- + CUAUUUAGAGUGUAUGGCAUGAGU 24

1887 20771

CFTR-

+ AGGGUCUCUCUAAGGUGU 18

IntronlO- 20772

712

5535.1 1888

CFTR- IntronlO- + UGAGGGUCUCUCUAAGGUGU 20

1889 20773

CFTR- IntronlO- + UGGGGAAAUCAGCACUCUAUU 21

1890 20774

CFTR- IntronlO- + UGUGGGGAAAUCAGCACUCUAUU 23

1891 20775

CFTR- IntronlO- + CUGUGGGGAAAUCAGCACUCUAUU 24

1892 20776

CFTR- IntronlO- + UGUAACUCUUUAUUCACUU 19

1893 20777

CFTR- IntronlO- + UUGUAACUCUUUAUUCACUU 20

1894 20778

CFTR- IntronlO- + UUUGUAACUCUUUAUUCACUU 21

1895 20779

CFTR- IntronlO- + UUUUGUAACUCUUUAUUCACUU 22

1896 20780

CFTR- IntronlO- + AUUUUGUAACUCUUUAUUCACUU 23

1897 20781

CFTR- IntronlO- + CAUUUUGUAACUCUUUAUUCACUU 24

1898 20782

CFTR- IntronlO- + UAUCAACCCUCUUUCCUU 18

1899 20783

CFTR- IntronlO- + UUAUCAACCCUCUUUCCUU 19

1900 20784

CFTR- IntronlO- + CUUAUCAACCCUCUUUCCUU 20

1901 20785

CFTR-

+ UCUUAUCAACCCUCUUUCCUU 21

IntronlO- 20786

713

5535.1 1902

CFTR- IntronlO- + UUCUUAUCAACCCUCUUUCCUU 22

1903 20787

CFTR- IntronlO- + CUUCUUAUCAACCCUCUUUCCUU 23

1904 20788

CFTR- IntronlO- + UCUUCUUAUCAACCCUCUUUCCUU 24

1905 20789

CFTR- IntronlO- + U U U AU CAACAUG AAGG U U 18

1906 20790

CFTR- IntronlO- + CUUUAUCAACAUGAAGGUU 19

1907 20791

CFTR-

+ CCUUUAUCAACAUGAAGGUU 20

lntronlO-555 19441

CFTR- IntronlO- - UGCUUUCAGGAG CCAAAAA 19

1908 20792

CFTR- IntronlO- - C U G C U U U CAG G AG CCAAAAA 20

1909 20793

CFTR- IntronlO- - ACUGCUUUCAGGAGCCAAAAA 21

1910 20794

CFTR- IntronlO- - CACUGCUUU CAG GAG CCAAAAA 22

1911 20795

CFTR- IntronlO- - ACACUGCUUUCAGGAGCCAAAAA 23

1912 20796

CFTR- IntronlO- - AACACUG CU U U CAGG AG CCAAAAA 24

1913 20797

CFTR- IntronlO- - UUAAACACUUCUGAGAAA 18

1914 20798

CFTR- IntronlO- - UUUAAACACUUCUGAGAAA 19

1915 20799

714

5535.1 CFTR- IntronlO- - AUUUAAACACUUCUGAGAAA 20

1096 19981

CFTR- IntronlO- - AUAAGAUUCU A A AG G AAA 18

1916 20800

CFTR- IntronlO- - UGGAUAAGAUUCUAAAGGAAA 21

1917 20801

CFTR- IntronlO- - CUGGAUAAGAUUCUAAAGGAAA 22

1918 20802

CFTR- IntronlO- - CAUGCCAUACACUCUAAA 18

1919 20803

CFTR- IntronlO- - UCAUGCCAUACACUCUAAA 19

1920 20804

CFTR- IntronlO- - CUCAUGCCAUACACUCUAAA 20

1921 20805

CFTR- IntronlO- - ACUCAUGCCAUACACUCUAAA 21

1922 20806

CFTR- IntronlO- - UACUCAUGCCAUACACUCUAAA 22

1923 20807

CFTR- IntronlO- - CGUACUCAUGCCAUACACUCUAAA 24

1924 20808

CFTR- IntronlO- - AGGUUUAAUUUUGUACAA 18

1925 20809

CFTR- IntronlO- - UAGGUUUAAUUUUGUACAA 19

1926 20810

CFTR-

- CUAGGUUUAAUUUUGUACAA 20

lntronlO-343 19229

CFTR- IntronlO- - UCUAGGUUUAAUUUUGUACAA 21

1927 20811

CFTR-

- UUCUAGGUUUAAUUUUGUACAA 22

IntronlO- 20812

715

5535.1 1928

CFTR- IntronlO- - CUUCUAGGUUUAAUUUUGUACAA 23

1929 20813

CFTR- IntronlO- - ACUUCUAGGUUUAAUUUUGUACAA 24

1930 20814

CFTR- IntronlO- - CUUUGAAGGAAGAUCCAA 18

1931 20815

CFTR- IntronlO- - UGCUUUGAAGGAAGAUCCAA 20

1932 20816

CFTR- IntronlO- - UAAUCAUCUAGGCUGCAA 18

1933 20817

CFTR- IntronlO- - AUAAUCAUCUAGGCUGCAA 19

1934 20818

CFTR- IntronlO- - AAUAAUCAUCUAGGCUGCAA 20

1935 20819

CFTR- IntronlO- - UAAUAAUCAUCUAGGCUGCAA 21

1936 20820

CFTR- IntronlO- - UUAAUAAUCAUCUAGGCUGCAA 22

1937 20821

CFTR- IntronlO- - AUUAAUAAUCAUCUAGGCUGCAA 23

1938 20822

CFTR- IntronlO- - UAUUAAUAAUCAUCUAGGCUGCAA 24

1939 20823

CFTR- IntronlO- - AGG AG AACCAU AU U U U G AAG AA 22

1940 20824

CFTR- IntronlO- - UGAGGAGAACCAUAUUUUGAAGAA 24

1941 20825

CFTR-

- AGGGUUGAUAAGAAGAGAA 19

IntronlO- 20826

716

5535.1 1942

CFTR- IntronlO- - AGAGGGUUGAUAAGAAGAGAA 21

1943 20827

CFTR- IntronlO- - AAGAGGGUUGAUAAGAAGAGAA 22

1944 20828

CFTR- IntronlO- - AAAGAGGGUUGAUAAGAAGAGAA 23

1945 20829

CFTR- IntronlO- - UGCUCUCUGACCACAUAA 18

1946 20830

CFTR- IntronlO- - UUGCUCUCUGACCACAUAA 19

1947 20831

CFTR- IntronlO- - CUUGCUCUCUGACCACAUAA 20

1948 20832

CFTR- IntronlO- - ACUUGCUCUCUGACCACAUAA 21

1949 20833

CFTR- IntronlO- - UACUUGCUCUCUGACCACAUAA 22

1950 20834

CFTR- IntronlO- - UGUACUUGCUCUCUGACCACAUAA 24

1951 20835

CFTR- IntronlO- - UAUAUGAUAUACUCUUAA 18

1952 20836

CFTR- IntronlO- - UGUAUAUGAUAUACUCUUAA 20

1953 20837

CFTR- IntronlO- - AUGUAUAUGAUAUACUCUUAA 21

1954 20838

CFTR- IntronlO- - CGGAUGUAUAUGAUAUACUCUUAA 24

1955 20839

CFTR-

- AACU CAU U AGG AAAAUG U ACA 21

IntronlO- 20840

717

5535.1 1956

CFTR- IntronlO- - CAACUCAUUAGGAAAAUGUACA 22

1957 20841

CFTR- IntronlO- - CCAACUCAUUAGGAAAAUGUACA 23

1958 20842

CFTR- IntronlO- - ACCAACU CAU U AGG AAAAUG U ACA 24

1959 20843

CFTR- IntronlO- - A U G A AG U U A A A A AC A U C A 18

1960 20844

CFTR- IntronlO- - UAUGAAGUU A A A A AC A U C A 19

1961 20845

CFTR- IntronlO- - AUAUGAAGUUAAAAACAUCA 20

1962 20846

CFTR- IntronlO- - AGUAUAGAAUUUUGCAUCA 19

1963 20847

CFTR- IntronlO- - UAGUAUAGAAUUUUGCAUCA 20

1964 20848

CFTR- IntronlO- - AGGUAGUAAUUGUGUUUCA 19

1965 20849

CFTR- IntronlO- - AAGGUAGUAAUUGUGUUUCA 20

1966 20850

CFTR- IntronlO- - AAAGGUAGUAAUUGUGUUUCA 21

1967 20851

CFTR- IntronlO- - AAAAGGUAGUAAUUGUGUUUCA 22

1968 20852

CFTR- IntronlO- - UGAAAAGGUAGUAAUUGUGUUUCA 24

1969 20853

CFTR-

- AGAGCCUUUUCUUUUUCA 18

IntronlO- 20854

718

5535.1 1970

CFTR- IntronlO- - AAGAGCCUUUUCUUUUUCA 19

1971 20855

CFTR- IntronlO- - AAAGAGCCUUUUCUUUUUCA 20

1972 20856

CFTR- IntronlO- - UCUAGCUAAAAUAUAAGA 18

1973 20857

CFTR- IntronlO- - AUCUAGCUAAAAUAUAAGA 19

1974 20858

CFTR- IntronlO- - CUUGACCAGAAUGAAAUUAGA 21

1975 20859

CFTR- IntronlO- - ACUUGACCAGAAUGAAAUUAGA 22

1976 20860

CFTR- IntronlO- - AACUUGACCAGAAUGAAAUUAGA 23

1977 20861

CFTR- IntronlO- - AAACUUGACCAGAAUGAAAUUAGA 24

1978 20862

CFTR- IntronlO- - AGGAAAAUGUACAAAGGA 18

1979 20863

CFTR- IntronlO- - UAGGAAAAUGUACAAAGGA 19

1980 20864

CFTR- IntronlO- - UU AGGAAAAUGUACAAAGGA 20

1981 20865

CFTR- IntronlO- - UGAUUCCAAGCUUUCUGGA 19

1982 20866

CFTR- IntronlO- - AUGAUUCCAAGCUUUCUGGA 20

1983 20867

CFTR-

- UAUACUCUUAAGUGAAUA 18

IntronlO- 20868

719

5535.1 1984

CFTR- IntronlO- - AUAUACUCUUAAGUGAAUA 19

1985 20869

CFTR- IntronlO- - UGAUAUACUCUUAAGUGAAUA 21

1986 20870

CFTR- IntronlO- - AUGAUAUACUCUUAAGUGAAUA 22

1987 20871

CFTR- IntronlO- - UAUGAUAUACUCUUAAGUGAAUA 23

1988 20872

CFTR- IntronlO- - AUAUGAUAUACUCUUAAGUGAAUA 24

1989 20873

CFTR- IntronlO- - CUAACCUUCAUGUUGAUA 18

1990 20874

CFTR- IntronlO- - CCUAACCUUCAUGUUGAUA 19

1991 20875

CFTR- IntronlO- - CCCUAACCUUCAUGUUGAUA 20

1992 20876

CFTR- IntronlO- - UGGAUAUUCUAUGAUAUA 18

1993 20877

CFTR- IntronlO- - AUGGAUAUUCUAUGAUAUA 19

1994 20878

CFTR- IntronlO- - UGGAUGGAUAUUCUAUGAUAUA 22

1995 20879

CFTR- IntronlO- - AUGGAUGGAUAUUCUAUGAUAUA 23

1996 20880

CFTR- IntronlO- - UAUGGAUGGAUAUUCUAUGAUAUA 24

1997 20881

CFTR-

- AUACUUUCUAGAAUUAUA 18

IntronlO- 20882

720

5535.1 1998

CFTR- IntronlO- - AAUACUUUCUAGAAUUAUA 19

1999 20883

CFTR- IntronlO- - AAAUACUUUCUAGAAUUAUA 20

2000 20884

CFTR- IntronlO- - UUUUGCUUGCUUUUUAUA 18

2001 20885

CFTR- IntronlO- - UUUUUGCUUGCUUUUUAUA 19

2002 20886

CFTR- IntronlO- - UCUGAGAAGACAAAGCUA 18

2003 20887

CFTR- IntronlO- - AGUCUGAGAAGACAAAGCUA 20

2004 20888

CFTR- IntronlO- - AAGUCUGAGAAGACAAAGCUA 21

2005 20889

CFTR- IntronlO- - AAAGUCUGAGAAGACAAAGCUA 22

2006 20890

CFTR- IntronlO- - A AAAG U C U GAG AAG AC AAAG C U A 23

2007 20891

CFTR- IntronlO- - UAAAAGUCUGAGAAGACAAAGCUA 24

2008 20892

CFTR- IntronlO- - AGUGAAGCAAUAUUAGUA 18

2009 20893

CFTR- IntronlO- - UAGUGAAGCAAUAUUAGUA 19

2010 20894

CFTR- IntronlO- - UU AGUGAAGCAAUAUUAGUA 20

2011 20895

CFTR-

- UUUAGUGAAGCAAUAUUAGUA 21

IntronlO- 20896

721

5535.1 2012

CFTR- IntronlO- - UUUUAGUGAAGCAAUAUUAGUA 22

2013 20897

CFTR- IntronlO- - AUUUUAGUGAAGCAAUAUUAGUA 23

2014 20898

CFTR- IntronlO- - UAUUUUAGUGAAGCAAUAUUAGUA 24

2015 20899

CFTR- IntronlO- - UAAUCGGCGGUGGAGGUA 18

2016 20900

CFTR-

- AGUAAUCGGCGGUGGAGGUA 20

lntronlO-389 19275

CFTR- IntronlO- - AAGUAAUCGGCGGUGGAGGUA 21

2017 20901

CFTR- IntronlO- - AGAAGUAAUCGGCGGUGGAGGUA 23

2018 20902

CFTR- IntronlO- - CAUUGCCUCACUAUGGUA 18

2019 20903

CFTR- IntronlO- - UCAUUGCCUCACUAUGGUA 19

2020 20904

CFTR- IntronlO- - AUCAUUGCCUCACUAUGGUA 20

2021 20905

CFTR- IntronlO- - UGAUCAUUGCCUCACUAUGGUA 22

2022 20906

CFTR- IntronlO- - UUGAUCAUUGCCUCACUAUGGUA 23

2023 20907

CFTR- IntronlO- - AUUGAUCAUUGCCUCACUAUGGUA 24

2024 20908

CFTR- IntronlO- - AACUGGGACUCAUAUGUA 18

2025 20909

722

5535.1 CFTR- IntronlO- - UAACUGGGACUCAUAUGUA 19

2026 20910

CFTR- IntronlO- - AUAACUGGGACUCAUAUGUA 20

2027 20911

CFTR- IntronlO- - AAUAACUGGGACUCAUAUGUA 21

2028 20912

CFTR- IntronlO- - UAAUAACUGGGACUCAUAUGUA 22

2029 20913

CFTR- IntronlO- - UGUAAUAACUGGGACUCAUAUGUA 24

2030 20914

CFTR- IntronlO- - AGGAAGAUCCAAUAGGAUUA 20

2031 20915

CFTR- IntronlO- - AAGGAAGAUCCAAUAGGAUUA 21

2032 20916

CFTR- IntronlO- - UGAAGGAAGAUCCAAUAGGAUUA 23

2033 20917

CFTR- IntronlO- - UUGAAGGAAGAUCCAAUAGGAUUA 24

2034 20918

CFTR- IntronlO- - UGCAGGAGGUGAGGGAUUA 19

2035 20919

CFTR-

- UUGCAGGAGGUGAGGGAUUA 20

lntronlO-394 19280

CFTR- IntronlO- - CAGCCAAUAAAAGGUUUGUUA 21

2036 20920

CFTR- IntronlO- - UCAGCCAAUAAAAGGUUUGUUA 22

2037 20921

CFTR- IntronlO- - U U CAG CCAAU AAAAGG U U UG U U A 23

2038 20922

CFTR-

- AUUCAGCCAAUAAAAGGUUUGUUA 24

IntronlO- 20923

723

5535.1 2039

CFTR- IntronlO- - AGUUAGCAAUGGUCUAAAC 19

2040 20924

CFTR- IntronlO- - AAGUUAGCAAUGGUCUAAAC 20

2041 20925

CFTR- IntronlO- - AUUCUGUUUAAAUAGCAC 18

2042 20926

CFTR-

- UGAUUCUGUUUAAAUAGCAC 20

lntronlO-410 19296

CFTR- IntronlO- - CUGAUUCUGUUUAAAUAGCAC 21

2043 20927

CFTR- IntronlO- - CCUGAUUCUGUUUAAAUAGCAC 22

2044 20928

CFTR- IntronlO- - CCCUGAUUCUGUUUAAAUAGCAC 23

2045 20929

CFTR- IntronlO- - CCCCUGAUUCUGUUUAAAUAGCAC 24

2046 20930

CFTR- IntronlO- - AGAGAAGGUCAAACUUGAC 19

2047 20931

CFTR- IntronlO- - UAGAGAAGGUCAAACUUGAC 20

2048 20932

CFTR- IntronlO- - AGUAGAGAAGGUCAAACUUGAC 22

2049 20933

CFTR- IntronlO- - U AG U AG AG AAGG U CAAACU UG AC 23

2050 20934

CFTR- IntronlO- - AUAGUAGAGAAGGUCAAACUUGAC 24

2051 20935

CFTR- IntronlO- - CUCUAUAUAAAGUGAUCC 18

2052 20936

724

5535.1 CFTR- IntronlO- - UCUCUAUAUAAAGUGAUCC 19

2053 20937

CFTR- IntronlO- - CUCUCUAUAUAAAGUGAUCC 20

2054 20938

CFTR- IntronlO- - UCUCUCUAUAUAAAGUGAUCC 21

2055 20939

CFTR- IntronlO- - UUCUCUCUAUAUAAAGUGAUCC 22

2056 20940

CFTR- IntronlO- - UUUCUCUCUAUAUAAAGUGAUCC 23

2057 20941

CFTR- IntronlO- - AUUUCUCUCUAUAUAAAGUGAUCC 24

2058 20942

CFTR- IntronlO- - AUUCUUUUGAUAUACUCC 18

2059 20943

CFTR- IntronlO- - UAUUCUUUUGAUAUACUCC 19

2060 20944

CFTR- IntronlO- - UUAUUCUUUUGAUAUACUCC 20

1213 20098

CFTR- IntronlO- - CUUAUUCUUUUGAUAUACUCC 21

2061 20945

CFTR- IntronlO- - CCUUAUUCUUUUGAUAUACUCC 22

2062 20946

CFTR- IntronlO- - UGCCUUAUUCUUUUGAUAUACUCC 24

2063 20947

CFTR- IntronlO- - UGCGCUUAUGAAACUUCC 18

2064 20948

CFTR- IntronlO- - UUGCGCUUAUGAAACUUCC 19

2065 20949

725

5535.1 CFTR- IntronlO- - CUUGCGCUUAUGAAACUUCC 20

2066 20950

CFTR- IntronlO- - UCUUGCGCUUAUGAAACUUCC 21

2067 20951

CFTR- IntronlO- - UGUCUUGCGCUUAUGAAACUUCC 23

2068 20952

CFTR- IntronlO- - AUGUCUUGCGCUUAUGAAACUUCC 24

2069 20953

CFTR- IntronlO- - AAACCAAACAAGCUUUCC 18

2070 20954

CFTR- IntronlO- - AAAACCAAACAAG CU U U CC 19

2071 20955

CFTR- IntronlO- - UAAAACCAAACAAGCUUUCC 20

2072 20956

CFTR- IntronlO- - CU U U U AAAACAAAAU AG C 18

2073 20957

CFTR- IntronlO- - AGCU U U U AAAACAAAAU AG C 20

1220 20105

CFTR- IntronlO- - AGGAAGACAGCUGGCUAUC 19

2074 20958

CFTR- IntronlO- - CAGGAAGACAGCUGGCUAUC 20

2075 20959

CFTR- IntronlO- - AGCAGGAAGACAGCUGGCUAUC 22

2076 20960

CFTR- IntronlO- - CAGCAGGAAGACAGCUGGCUAUC 23

2077 20961

CFTR- IntronlO- - ACAGCAGGAAGACAGCUGGCUAUC 24

2078 20962

726

5535.1 CFTR- IntronlO- - AGCUGGCUAUCCAGGAUUC 19

2079 20963

CFTR-

- CAGCUGGCUAUCCAGGAUUC 20

lntronlO-441 19327

CFTR- IntronlO- - ACAGCUGGCUAUCCAGGAUUC 21

2080 20964

CFTR- IntronlO- - AGACAGCUGGCUAUCCAGGAUUC 23

2081 20965

CFTR- IntronlO- - AAGACAGCUGGCUAUCCAGGAUUC 24

2082 20966

CFTR- IntronlO- - UUCUGUAAUUUUUGCUUC 18

2083 20967

CFTR- IntronlO- - AGACUUUGUAGUGAUCUUC 19

2084 20968

CFTR- IntronlO- - AAGACUUUGUAGUGAUCUUC 20

2085 20969

CFTR- IntronlO- - AGAAGACUUUGUAGUGAUCUUC 22

2086 20970

CFTR- IntronlO- - AGCUUUUCAAAAUACUUUC 19

2087 20971

CFTR- IntronlO- - AAGCUUUUCAAAAUACUUUC 20

2088 20972

CFTR- IntronlO- - UGAAGCUUUUCAAAAUACUUUC 22

2089 20973

CFTR- IntronlO- - UUGAAGCUUUUCAAAAUACUUUC 23

2090 20974

CFTR- IntronlO- - CUUGAAGCUUUUCAAAAUACUUUC 24

2091 20975

CFTR-

- AACAG U ACAAG AAAAAAG 18

IntronlO- 20976

727

5535.1 2092

CFTR- IntronlO- - UAACAGUACAAGAAAAAAG 19

2093 20977

CFTR- IntronlO- - UGCCAUUAACAGAUAAAG 18

2094 20978

CFTR- IntronlO- - U U GCCAU U AACAG AU AAAG 19

2095 20979

CFTR- IntronlO- - UU UGCCAUUAACAGAUAAAG 20

2096 20980

CFTR- IntronlO- - AUAUGAGAAAAGUCACAG 18

2097 20981

CFTR- IntronlO- - CAUAUGAGAAAAGUCACAG 19

2098 20982

CFTR- IntronlO- - UGGCAUAUGAGAAAAGUCACAG 22

2099 20983

CFTR- IntronlO- - AUGGCAUAUGAGAAAAGUCACAG 23

2100 20984

CFTR- IntronlO- - AAUGGCAUAUGAGAAAAGUCACAG 24

2101 20985

CFTR- IntronlO- - CCAACUGAUGUCAAGCAG 18

2102 20986

CFTR- IntronlO- - CCCAACUGAUGU CAAG C AG 19

2103 20987

CFTR- IntronlO- - ACCCAACUGAUGUCAAGCAG 20

2104 20988

CFTR- IntronlO- - AACCCAACUGAUGUCAAGCAG 21

2105 20989

CFTR-

- CGGAACCCAACUGAUGUCAAGCAG 24

IntronlO- 20990

728

5535.1 2106

CFTR- IntronlO- - AGUAUUAGAGGUUAAGGAG 19

2107 20991

CFTR- IntronlO- - AAGUAUUAGAGGUUAAGGAG 20

2108 20992

CFTR- IntronlO- - UAAGUAUUAGAGGUUAAGGAG 21

2109 20993

CFTR- IntronlO- - CUAAGUAUUAGAGGUUAAGGAG 22

2110 20994

CFTR- IntronlO- - UCUAAGUAUUAGAGGUUAAGGAG 23

2111 20995

CFTR- IntronlO- - UUCUAAGUAUUAGAGGUUAAGGAG 24

2112 20996

CFTR- IntronlO- - AGUCUUUUCCUCUUAAUAG 19

2113 20997

CFTR- IntronlO- - AAGUCUUUUCCUCUUAAUAG 20

2114 20998

CFTR- IntronlO- - UGAAGUCUUUUCCUCUUAAUAG 22

2115 20999

CFTR- IntronlO- - CUGAAGUCUUUUCCUCUUAAUAG 23

2116 21000

CFTR- IntronlO- - CCUGAAGUCUUUUCCUCUUAAUAG 24

2117 21001

CFTR- IntronlO- - UGAAAAGCAGCUAUGAAGG 19

2118 21002

CFTR- IntronlO- - AUGAAAAGCAGCUAUGAAGG 20

2119 21003

CFTR-

- UAUGAAAAGCAGCUAUGAAGG 21

IntronlO- 21004

729

5535.1 2120

CFTR- IntronlO- - UUAUGAAAAGCAGCUAUGAAGG 22

2121 21005

CFTR- IntronlO- - CUUAUGAAAAGCAGCUAUGAAGG 23

2122 21006

CFTR- IntronlO- - U U U CAACU U AU ACACAGG 18

2123 21007

CFTR- IntronlO- - AUUUCAACUUAUACACAGG 19

2124 21008

CFTR-

- CAU U U CAACU UAU ACACAGG 20

lntronlO-468 19354

CFTR- IntronlO- - UCAUUUCAACUUAUACACAGG 21

2125 21009

CFTR- IntronlO- - AUCAUUUCAACUUAUACACAGG 22

2126 21010

CFTR- IntronlO- - UAUCAUUUCAACUUAUACACAGG 23

2127 21011

CFTR- IntronlO- - AUAUCAUUUCAACUUAUACACAGG 24

2128 21012

CFTR- IntronlO- - UGGCAUAGAGUAAGACAGG 19

2129 21013

CFTR- IntronlO- - CUGGCAUAGAGUAAGACAGG 20

2130 21014

CFTR- IntronlO- - AGGCUGGCAUAGAGUAAGACAGG 23

2131 21015

CFTR- IntronlO- - AAUAAAUUUGGUGUCAGG 18

2132 21016

CFTR- IntronlO- - CAAUAAAUUUGGUGUCAGG 19

2133 21017

730

5535.1 CFTR- IntronlO- - UCAAUAAAUUUGGUGUCAGG 20

2134 21018

CFTR- IntronlO- - CUCAAUAAAUUUGGUGUCAGG 21

2135 21019

CFTR- IntronlO- - ACUCAAUAAAUUUGGUGUCAGG 22

2136 21020

CFTR- IntronlO- - CACUCAAUAAAUUUGGUGUCAGG 23

2137 21021

CFTR- IntronlO- - CCACUCAAUAAAUUUGGUGUCAGG 24

2138 21022

CFTR- IntronlO- - UGGUAGUGUGAAGAUGGGG 19

2139 21023

CFTR- IntronlO- - CUGGUAGUGUGAAGAUGGGG 20

2140 21024

CFTR- IntronlO- - AGGGAAUGCAGACUCUGGG 19

2141 21025

CFTR- IntronlO- - UAGGGAAUGCAGACUCUGGG 20

2142 21026

CFTR- IntronlO- - UU AGGGAAUGCAGACUCUGGG 21

2143 21027

CFTR- IntronlO- - AUUAGGGAAUGCAGACUCUGGG 22

2144 21028

CFTR- IntronlO- - UGGGGGAGCCCCAUAAAUG 19

2145 21029

CFTR- IntronlO- - UUUUUAUGUAACAAUAUG 18

2146 21030

CFTR- IntronlO- - CUUUUUAUGUAACAAUAUG 19

2147 21031

731

5535.1 CFTR- IntronlO- - UCUUUUUAUGUAACAAUAUG 20

2148 21032

CFTR- IntronlO- - CUCUUUUUAUGUAACAAUAUG 21

2149 21033

CFTR- IntronlO- - UCUCUUUUUAUGUAACAAUAUG 22

2150 21034

CFTR- IntronlO- - CUCUCUUUUUAUGUAACAAUAUG 23

2151 21035

CFTR- IntronlO- - CCUCUCUUUUUAUGUAACAAUAUG 24

2152 21036

CFTR- IntronlO- - UGAGAUUAGAGGCCACUG 18

2153 21037

CFTR- IntronlO- - UGCACAUAUGUUCAGACUG 19

2154 21038

CFTR- IntronlO- - UUGCACAUAUGUUCAGACUG 20

2155 21039

CFTR- IntronlO- - CUUGCACAUAUGUUCAGACUG 21

2156 21040

CFTR- IntronlO- - ACUUGCACAUAUGUUCAGACUG 22

2157 21041

CFTR- IntronlO- - UGUUAAAGAAUGACUGUG 18

2158 21042

CFTR- IntronlO- - UUGUUAAAGAAUGACUGUG 19

2159 21043

CFTR- IntronlO- - UU UGUUAAAGAAUGACUGUG 20

2160 21044

CFTR-

- UGGCAUCUCACCAGUGUGUG 20

lntronlO-492 19378

CFTR-

- AUGGCAUCUCACCAGUGUGUG 21

IntronlO- 21045

732

5535.1 2161

CFTR- IntronlO- - UAUGGCAUCUCACCAGUGUGUG 22

2162 21046

CFTR- IntronlO- - UUAUGGCAUCUCACCAGUGUGUG 23

2163 21047

CFTR- IntronlO- - CUUAUGGCAUCUCACCAGUGUGUG 24

2164 21048

CFTR- IntronlO- - UGAGGAGAACCAUAUUUUG 19

2165 21049

CFTR- IntronlO- - AUGAGGAGAACCAUAUUUUG 20

2166 21050

CFTR- IntronlO- - AGAUGAGGAGAACCAUAUUUUG 22

2167 21051

CFTR- IntronlO- - AAGAUGAGGAGAACCAUAUUUUG 23

2168 21052

CFTR- IntronlO- - UAAGAUGAGGAGAACCAUAUUUUG 24

2169 21053

CFTR- IntronlO- - CCAUAAAUGUUGAAUAAU 18

2170 21054

CFTR- IntronlO- - CCCAUAAAUGUUGAAUAAU 19

2171 21055

CFTR- IntronlO- - CCCCAUAAAUGUUGAAUAAU 20

1331 20216

CFTR- IntronlO- - AGCCCCAUAAAUGUUGAAUAAU 22

2172 21056

CFTR- IntronlO- - AGAUUUUUUCCCAUGUAAU 19

2173 21057

CFTR-

- CAGAUUUUUUCCCAUGUAAU 20

IntronlO- 21058

733

5535.1 2174

CFTR- IntronlO- - AUCACUAUUGAUUGACAU 18

2175 21059

CFTR- IntronlO- - AAUCACUAUUGAUUGACAU 19

2176 21060

CFTR- IntronlO- - UGAAUCACUAUUGAUUGACAU 21

2177 21061

CFTR- IntronlO- - AUGAAUCACUAUUGAUUGACAU 22

2178 21062

CFTR- IntronlO- - AAUGAAUCACUAUUGAUUGACAU 23

2179 21063

CFTR- IntronlO- - UAAUGAAUCACUAUUGAUUGACAU 24

2180 21064

CFTR- IntronlO- - UAGUUUCUAUUAAUAGAU 18

2181 21065

CFTR- IntronlO- - UGUAGUUUCUAUUAAUAGAU 20

2182 21066

CFTR- IntronlO- - CGUGUAGUUUCUAUUAAUAGAU 22

2183 21067

CFTR- IntronlO- - UCGUGUAGUUUCUAUUAAUAGAU 23

2184 21068

CFTR- IntronlO- - UUCGUGUAGUUUCUAUUAAUAGAU 24

2185 21069

CFTR- IntronlO- - AGAAAGAGCUUUCUAGUAU 19

2186 21070

CFTR- IntronlO- - AAAGCUGUGCAUUUUCCU 18

2187 21071

CFTR-

- AAAAGCUGUGCAUUUUCCU 19

IntronlO- 21072

734

5535.1 2188

CFTR- IntronlO- - AAAAAGCUGUGCAUUUUCCU 20

2189 21073

CFTR- IntronlO- - UGUUCAAAUUAUUUCUACUGCU 22

2190 21074

CFTR- IntronlO- - UUGUUCAAAUUAUUUCUACUGCU 23

2191 21075

CFTR- IntronlO- - UGUAGGCUAUAUGUAUCU 18

2192 21076

CFTR- IntronlO- - CUGUAGGCUAUAUGUAUCU 19

2193 21077

CFTR- IntronlO- - UCUGUAGGCUAUAUGUAUCU 20

2194 21078

CFTR- IntronlO- - AGACUAAGGCUUAUUUCU 18

2195 21079

CFTR- IntronlO- - AAGACUAAGGCUUAUUUCU 19

2196 21080

CFTR- IntronlO- - AAAGACUAAGGCUUAUUUCU 20

2197 21081

CFTR- IntronlO- - UAAAGACUAAGGCUUAUUUCU 21

2198 21082

CFTR- IntronlO- - CGUAAAGACUAAGGCUUAUUUCU 23

2199 21083

CFTR- IntronlO- - UCGUAAAGACUAAGGCUUAUUUCU 24

2200 21084

CFTR- IntronlO- - A AG A AG AG A A AG G G G U G U 18

2201 21085

CFTR-

- U A AG A AG AG A A AG G G G U G U 19

IntronlO- 21086

735

5535.1 2202

CFTR- IntronlO- - A U A AG A AG AG A A AG G G G U G U 20

1378 20262

CFTR- IntronlO- - UGAUAAGAAGAGAAAGGGGUGU 22

2203 21087

CFTR- IntronlO- - UUGAUAAGAAGAGAAAGGGGUGU 23

2204 21088

CFTR- IntronlO- - AGUUGUUAUCUCUGAAAUU 19

2205 21089

CFTR- IntronlO- - AAGUUGUUAUCUCUGAAAUU 20

2206 21090

CFTR- IntronlO- - CAAGUUGUUAUCUCUGAAAUU 21

2207 21091

CFTR- IntronlO- - UCAAGUUGUUAUCUCUGAAAUU 22

2208 21092

CFTR- IntronlO- - AUCAAGUUGUUAUCUCUGAAAUU 23

2209 21093

CFTR- IntronlO- - UAUCAAGUUGUUAUCUCUGAAAUU 24

2210 21094

CFTR- IntronlO- - ACGGUAAGCUCAAGCAUU 18

2211 21095

CFTR- IntronlO- - UACGGUAAGCUCAAGCAUU 19

2212 21096

CFTR- IntronlO- - UUACGGUAAGCUCAAGCAUU 20

2213 21097

CFTR- IntronlO- - AUUACGGUAAGCUCAAGCAUU 21

2214 21098

CFTR-

- UAUUACGGUAAGCUCAAGCAUU 22

IntronlO- 21099

736

5535.1 2215

CFTR- IntronlO- - CUAUUACGGUAAGCUCAAGCAUU 23

2216 21100

CFTR- IntronlO- - CUGCCUUUUAGUAGUAUU 18

2217 21101

CFTR- IntronlO- - AGGCUGCCUUUUAGUAGUAUU 21

2218 21102

CFTR- IntronlO- - AGGAGGCUGCCUUUUAGUAGUAUU 24

2219 21103

CFTR- IntronlO- - AGAUUAGCUUAUAUACUU 18

2220 21104

CFTR- IntronlO- - UAGAUUAGCUUAUAUACUU 19

2221 21105

CFTR-

- AUAGAUUAGCUUAUAUACUU 20

lntronlO-550 19436

CFTR- IntronlO- - AAUAGAUUAGCUUAUAUACUU 21

2222 21106

CFTR- IntronlO- - UGAAUAGAUUAGCUUAUAUACUU 23

2223 21107

CFTR- IntronlO- - UUGAAUAGAUUAGCUUAUAUACUU 24

2224 21108

CFTR- IntronlO- - UUUUCCAAGCGGUCCCUU 18

2225 21109

CFTR- IntronlO- - UUUUUCCAAGCGGUCCCUU 19

2226 21110

CFTR- IntronlO- - UUUUUUCCAAGCGGUCCCUU 20

2227 21111

CFTR- IntronlO- - UUUUUUUCCAAGCGGUCCCUU 21

2228 21112

737

5535.1 CFTR- IntronlO- - UUUUUUUUCCAAGCGGUCCCUU 22

2229 21113

CFTR- IntronlO- - AUUUUUUUUCCAAGCGGUCCCUU 23

2230 21114

CFTR- IntronlO- - AAUUUUUUUUCCAAGCGGUCCCUU 24

2231 21115

CFTR- IntronlO- - AGAGGAAGGCAGUGGUCCCUU 21

2232 21116

CFTR- IntronlO- - UAGAGGAAGGCAGUGGUCCCUU 22

2233 21117

CFTR- IntronlO- - UUAGAGGAAGGCAGUGGUCCCUU 23

2234 21118

CFTR- IntronlO- - AGAUGUGCAAAAAUAGCUU 19

2235 21119

CFTR-

- UAGAUGUGCAAAAAUAGCUU 20

lntronlO-552 19438

CFTR- IntronlO- - AUAGAUGUGCAAAAAUAGCUU 21

2236 21120

CFTR- IntronlO- - UGAUAGAUGUGCAAAAAUAGCUU 23

2237 21121

CFTR- IntronlO- - AUGAUAGAUGUGCAAAAAUAGCUU 24

2238 21122

CFTR- IntronlO- - ACAUGACCUUCCUUUCUU 18

2239 21123

CFTR- IntronlO- - UACAUGACCUUCCUUUCUU 19

2240 21124

CFTR- IntronlO- - UUACAUGACCUUCCUUUCUU 20

2241 21125

CFTR-

- UGUUACAUGACCUUCCUUUCUU 22

IntronlO- 21126

738

5535.1 2242

CFTR- IntronlO- - CUGUUACAUGACCUUCCUUUCUU 23

2243 21127

CFTR- IntronlO- - UCUGUUACAUGACCUUCCUUUCUU 24

2244 21128

CFTR- IntronlO- - UAAUGGGAGAAACAGGUU 18

2245 21129

CFTR- IntronlO- - AUAAUGGGAGAAACAGGUU 19

2246 21130

CFTR- IntronlO- - AGCACUGGAGUUACCUGUU 19

2247 21131

CFTR- IntronlO- - UAGCACUGGAGUUACCUGUU 20

2248 21132

CFTR- IntronlO- - AUAGCACUGGAGUUACCUGUU 21

2249 21133

CFTR- IntronlO- - AAUAGCACUGGAGUUACCUGUU 22

2250 21134

CFTR- IntronlO- - AAAUAGCACUGGAGUUACCUGUU 23

2251 21135

CFTR- IntronlO- - UAAAUAGCACUGGAGUUACCUGUU 24

2252 21136

CFTR- IntronlO- - CAAAUAGUUUUAUCAAUAUUU 21

2253 21137

CFTR- IntronlO- - UGCAAAUAGUUUUAUCAAUAUUU 23

2254 21138

CFTR- IntronlO- - CUGCAAAUAGUUUUAUCAAUAUUU 24

2255 21139

CFTR-

- UUGGAUGGAGCUUGGUUU 18

IntronlO- 21140

739

5535.1 2256

CFTR- IntronlO- - UUUGGAUGGAGCUUGGUUU 19

2257 21141

CFTR-

- UUUUGGAUGGAGCUUGGUUU 20

lntronlO-563 19449

CFTR- IntronlO- - AGGUUUUGGAUGGAGCUUGGUUU 23

2258 21142

CFTR- IntronlO- - CAGGUUUUGGAUGGAGCUUGGUUU 24

2259 21143

CFTR- IntronlO- - UG U CCU CCACAAAU AU U U U 19

2260 21144

CFTR- IntronlO- - AUGUCCUCCACAAAUAUUUU 20

2261 21145

Table 41C provides exemplary targeting domains for correcting a mutation (e.g., 3272- 26->G) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within intron 10, start with a 5'G and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through

complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 41C

740

5535.1 CFTR- IntronlO- + GGACAGAUGAGAGACAGUAAAGAA 24

2265 21149

CFTR- IntronlO- + GUGUUCUCACAUGGCAGAA 19

2266 21150

CFTR- IntronlO- + GCUGUGUUCUCACAUGGCAGAA 22

2267 21151

CFTR- IntronlO- + GUUCUUAGGGUGGGAUAUGGAGAA 24

2268 21152

CFTR- IntronlO- + G A AG A A A AG U A U C A A U A A 18

2269 21153

CFTR- IntronlO- + GGAAGAAAAGUAUCAAUAA 19

2270 21154

CFTR- IntronlO- + GUUUUUACCAUUAUCUACACA 21

2271 21155

CFTR- IntronlO- + GAUAUGGAGAAGAGGAUGACCA 22

2272 21156

CFTR- IntronlO- + GGAUAUGGAGAAGAGGAUGACCA 23

2273 21157

CFTR- IntronlO- + GGGAUAUGGAGAAGAGGAUGACCA 24

2274 21158

CFTR- IntronlO- + GAAGUUCAGCCUGGGUGA 18

2275 21159

CFTR- IntronlO- + GCAAAAAUUACAGAACCUAUA 21

2276 21160

CFTR- IntronlO- + GAAGCAAAAAUUACAGAACCUAUA 24

2277 21161

CFTR- IntronlO- + GCUUCCUCCCUUGUCUCCCUA 21

2278 21162

741

5535.1 CFTR- IntronlO- + GUCUUCUCAGACUUUUAUUUUA 22

2279 21163

CFTR- IntronlO- + GUUUCCAAAUUUUUUUUA 18

2280 21164

CFTR- IntronlO- + GACAAGUUUCCAAAUUUUUUUUA 23

2281 21165

CFTR- IntronlO- + GUGUGGCUUAUAAACAAC 18

2282 21166

CFTR- IntronlO- + GAACUGUGUGGCUUAUAAACAAC 23

2283 21167

CFTR- IntronlO- + GAAGAUACUAAAAAAAGUUAC 21

2284 21168

CFTR- IntronlO- + GGAAGAUACUAAAAAAAGUUAC 22

2285 21169

CFTR- IntronlO- + GGGAAGAUACUAAAAAAAGUUAC 23

2286 21170

CFTR- IntronlO- + GAAAGGUCAAUUGAGCCC 18

2287 21171

CFTR- IntronlO- + GGAAAGGUCAAUUGAGCCC 19

2288 21172

CFTR- IntronlO- + GCGGAAAGGUCAAUUGAGCCC 21

2289 21173

CFTR- IntronlO- + GAAGCGGAAAGGUCAAUUGAGCCC 24

2290 21174

CFTR- IntronlO- + GCUACUUGGAAGACUCUUCC 20

2291 21175

CFTR- IntronlO- + GAUCACACCACUGAAGUUCAGC 22

2292 21176

742

5535.1 CFTR- IntronlO- + GAGUUUCACUGUGUUAGC 18

2293 21177

CFTR- IntronlO- + GGAGUUUCACUGUGUUAGC 19

2294 21178

CFTR- IntronlO- + GACGGAGUUUCACUGUGUUAGC 22

2295 21179

CFTR- IntronlO- + GAGACGGAGUUUCACUGUGUUAGC 24

2296 21180

CFTR- IntronlO- + GUCUCACUCUGUCACCCAGGC 21

2297 21181

CFTR- IntronlO- + GAGUCUCACUCUGUCACCCAGGC 23

2298 21182

CFTR- IntronlO- + GCCUCUGCCUCCAAAAGUGC 20

2299 21183

CFTR- IntronlO- + GCCAUUCUCCUGCCUCAGCCUC 22

2300 21184

CFTR- IntronlO- + GCUCACUGCAAGUUCUGCCUC 21

2301 21185

CFTR- IntronlO- + GGCUCACUGCAAGUUCUGCCUC 22

2302 21186

CFTR- IntronlO- + GAUCUUCCUUCAAAGCAUGUC 21

2303 21187

CFTR- IntronlO- + GGAUCUUCCUUCAAAGCAUGUC 22

2304 21188

CFTR- IntronlO- + GUGAUAUUUUUCAUUAUGAUUC 22

2305 21189

CFTR- IntronlO- + GGUGAUAUUUUUCAUUAUGAUUC 23

2306 21190

743

5535.1 CFTR- IntronlO- + GCUACUUGGGAGGCUGAGGCAG 22

2307 21191

CFTR- IntronlO- + GCUACUUGGGAGGGUGAGGCAG 22

2308 21192

CFTR-

+ GUUUGUGUUUUUUGUAGAGG 20

lntronlO-701 19587

CFTR- IntronlO- + GCACUUUGGGAGGCCGAGGCGG 22

2309 21193

CFTR- IntronlO- + GAACAAAAAUUAAAACUAAUGG 22

2310 21194

CFTR- IntronlO- + GUGAACAAAAAUUAAAACUAAUGG 24

2311 21195

CFTR- IntronlO- + GUAGUCCCAGCUACUUGG 18

2312 21196

CFTR- IntronlO- + GCCUGUAGUCCCAGCUACUUGG 22

2313 21197

CFTR- IntronlO- + GUGCCUGUAGUCCCAGCUACUUGG 24

2314 21198

CFTR- IntronlO- + GCAAUACCAUCACCUUGGGAAU 22

2315 21199

CFTR- IntronlO- + GAAUUAGGAUUUCAACAU 18

2316 21200

CFTR- IntronlO- + GGAAUUAGGAUUUCAACAU 19

2317 21201

CFTR- IntronlO- + GGGAAUUAGGAUUUCAACAU 20

2318 21202

CFTR- IntronlO- + GAUCAAGGUGCCAGCAGAU 19

2319 21203

CFTR-

+ GUGAUAGUUGCACAACUAU 19

IntronlO- 21204

744

5535.1 2320

CFTR- IntronlO- + GGUGAUAGUUGCACAACUAU 20

2321 21205

CFTR- IntronlO- + GAGGUGAUAGUUGCACAACUAU 22

2322 21206

CFTR- IntronlO- + GGAGGUGAUAGUUGCACAACUAU 23

2323 21207

CFTR- IntronlO- + GUUUAUUUACAUUUCUCUUUACU 23

2324 21208

CFTR- IntronlO- + GAAAAUGU UAAAU U U U CCCU 20

2325 21209

CFTR- IntronlO- + GAAAU U U AAU UGCCAG UAAG U CU 23

2326 21210

CFTR- IntronlO- + GUUCUCACAUGGCAGAAAGGGGU 23

2327 21211

CFTR- IntronlO- + GCAUCACUAGUGGCACUUUGU 21

2328 21212

CFTR- IntronlO- + GUGCAUCACUAGUGGCACUUUGU 23

2329 21213

CFTR- IntronlO- + GACCCUUUAUCAACAUGAAGGUU 23

2330 21214

CFTR- IntronlO- + GAAAUAUAGAUUUAAUCUUAUUU 23

2331 21215

CFTR- IntronlO- + GGAAAUAUAGAUUUAAUCUUAUUU 24

2332 21216

CFTR- IntronlO- + GUAUUUCUAGGCUAGACAGUUU 22

2333 21217

CFTR-

+ GGUAUUUCUAGGCUAGACAGUUU 23

IntronlO- 21218

745

5535.1 2334

CFTR- IntronlO- + GUUCAAGCCUGUAUUGUUU 19

2335 21219

CFTR- IntronlO- + GCAGUUCAAGCCUGUAUUGUUU 22

2336 21220

CFTR- IntronlO- - G AAU AU U U AAACACU U CUG AG AAA 24

2337 21221

CFTR- IntronlO- - GACAUGCUUUGAAGGAAGAUCCAA 24

2338 21222

CFTR- IntronlO- - G AACCAU AU U U UG AAG AA 18

2339 21223

CFTR- IntronlO- - G AG AACCAU AU U U UG AAG AA 20

2340 21224

CFTR- IntronlO- - GUAUAUUAUAGAAAUUUAA 19

2341 21225

CFTR- IntronlO- - GGUAUAUUAUAGAAAUUUAA 20

2342 21226

CFTR- IntronlO- - GACAGGUAUAUUAUAGAAAUUUAA 24

2343 21227

CFTR- IntronlO- - GUGGAUUUUUGACUAUACA 19

2344 21228

CFTR- IntronlO- - GAGGUCACUGAGGCUGGCA 19

2345 21229

CFTR- IntronlO- - GGAGGUCACUGAGGCUGGCA 20

2346 21230

CFTR- IntronlO- - GUAAGGAGGUCACUGAGGCUGGCA 24

2347 21231

CFTR-

- GAUAUGAAGUUAAAAACAUCA 21

IntronlO- 21232

746

5535.1 2348

CFTR- IntronlO- - GAGAUAUGAAGUUAAAAACAUCA 23

2349 21233

CFTR- IntronlO- - GG AG AU AUG AAG U U AAAAACAU CA 24

2350 21234

CFTR- IntronlO- - GACCAGAAUGAAAUUAGA 18

2351 21235

CFTR- IntronlO- - GAUGAUUCCAAGCUUUCUGGA 21

2352 21236

CFTR- IntronlO- - G AAAU AAAU U U AAAG ACAUG A 21

2353 21237

CFTR- IntronlO- - GG AAAU AAAU U U AAAG ACAUG A 22

2354 21238

CFTR- IntronlO- - G AGG AAAU AAAU U U AAAG ACAUG A 24

2355 21239

CFTR- IntronlO- - GAGAAGACAAAGCUAGUGA 19

2356 21240

CFTR- IntronlO- - GUCUGAGAAGACAAAGCUAGUGA 23

2357 21241

CFTR- IntronlO- - GCACUCUAGCCUGGGUGA 18

2358 21242

CFTR- IntronlO- - GCCACUGCACUCUAGCCUGGGUGA 24

2359 21243

CFTR- IntronlO- - GCACCCCUAACCUUCAUGUUGAUA 24

2360 21244

CFTR- IntronlO- - GACUUGCAGGAGGUGAGGGAUUA 23

2361 21245

CFTR-

- GCCAAUAAAAGGUUUGUUA 19

IntronlO- 21246

747

5535.1 2362

CFTR- IntronlO- - GCAUAUAUAUAUUUUUAAC 19

2363 21247

CFTR- IntronlO- - GUGGAGUCAAAAAUUAUAC 19

2364 21248

CFTR- IntronlO- - GUUUAGUGCAAUGCCAUAAACC 22

2365 21249

CFTR- IntronlO- - GAAAAAGUAAGAUAUGCC 18

2366 21250

CFTR- IntronlO- - GGUGAAUUGCUUGAGUCC 18

2367 21251

CFTR- IntronlO- - GCAGGUGAAUUGCUUGAGUCC 21

2368 21252

CFTR- IntronlO- - GGCAGGUGAAUUGCUUGAGUCC 22

2369 21253

CFTR- IntronlO- - GAGGCAGGUGAAUUGCUUGAGUCC 24

2370 21254

CFTR- IntronlO- - GAAAACAAAUUUUCUUUGUUUUCC 24

2371 21255

CFTR- IntronlO- - GCGCCACUGCACUCUAGC 18

2372 21256

CFTR- IntronlO- - GAUCGCGCCACUGCACUCUAGC 22

2373 21257

CFTR- IntronlO- - GAGAUCGCGCCACUGCACUCUAGC 24

2374 21258

CFTR- IntronlO- - GGGUUUCACCGUUUUAGC 18

2375 21259

CFTR-

- GGGGUUUCACCGUUUUAGC 19

IntronlO- 21260

748

5535.1 2376

CFTR- IntronlO- - GACGGGGUUUCACCGUUUUAGC 22

2377 21261

CFTR- IntronlO- - GAGACGGGGUUUCACCGUUUUAGC 24

2378 21262

CFTR- IntronlO- - GUCUCGCUCUGUCGCCCAGGC 21

2379 21263

CFTR- IntronlO- - GAGUCUCGCUCUGUCGCCCAGGC 23

2380 21264

CFTR- IntronlO- - GGAGUCUCGCUCUGUCGCCCAGGC 24

2381 21265

CFTR- IntronlO- - GGGUUUCACCAUGUUGGC 18

2382 21266

CFTR- IntronlO- - GGGGUUUCACCAUGUUGGC 19

2383 21267

CFTR- IntronlO- - GACGGGGUUUCACCAUGUUGGC 22

2384 21268

CFTR- IntronlO- - GAGACGGGGUUUCACCAUGUUGGC 24

2385 21269

CFTR-

- GCCUCGGCCUCCCAAAGUGC 20

lntronlO-686 19572

CFTR- IntronlO- - GCCCGCCUCGGCCUCCCAAAGUGC 24

2386 21270

CFTR- IntronlO- - GCAGAGGCAGGUGAAUUGC 19

2387 21271

CFTR- IntronlO- - GGCAGAGGCAGGUGAAUUGC 20

2388 21272

CFTR- IntronlO- - GAGGCAGAGGCAGGUGAAUUGC 22

2389 21273

749

5535.1 CFTR- IntronlO- - GGAGGCAGAGGCAGGUGAAUUGC 23

2390 21274

CFTR- IntronlO- - GCUCACUGCAAGCUCCGCCUC 21

2391 21275

CFTR- IntronlO- - GGCUCACUGCAAGCUCCGCCUC 22

2392 21276

CFTR- IntronlO- - G U UG U AACAG U ACAAG AAAAAAG 23

2393 21277

CFTR- IntronlO- - GCUUUGCCAUUAACAGAUAAAG 22

2394 21278

CFTR- IntronlO- - GCACUUUUGGAGGCAGAGGCAG 22

2395 21279

CFTR- IntronlO- - GCUACUCGGGAGGCUGAGGCAG 22

2396 21280

CFTR- IntronlO- - GACAAGGGAGGAAGCAAGGAG 21

2397 21281

CFTR- IntronlO- - GAGACAAGGGAGGAAGCAAGGAG 23

2398 21282

CFTR- IntronlO- - GGAGACAAGGGAGGAAGCAAGGAG 24

2399 21283

CFTR- IntronlO- - GACAUCCAAAUAGAGAUGUUAG 22

2400 21284

CFTR- IntronlO- - GCAUAGAGUAAGACAGGGAGGG 22

2401 21285

CFTR- IntronlO- - GGCAUAGAGUAAGACAGGGAGGG 23

2402 21286

CFTR- IntronlO- - GCAUAGUAUUCUAUCAUAUGG 21

2403 21287

750

5535.1 CFTR- IntronlO- - GAUGCAUAGUAUUCUAUCAUAUGG 24

2404 21288

CFTR- IntronlO- - GCUUUCUGGACUGAGUAACUGG 22

2405 21289

CFTR- IntronlO- - GUAUAUAUGUGUGUCUGG 18

2406 21290

CFTR- IntronlO- - GUAUGUAUAUAUGUGUGUCUGG 22

2407 21291

CFTR- IntronlO- - GCCCAGGCUGGAGUGCAGUGG 21

2408 21292

CFTR- IntronlO- - GUCGCCCAGGCUGGAGUGCAGUGG 24

2409 21293

CFTR- IntronlO- - GCUACUUGGGAGGCUGAGGUGG 22

2410 21294

CFTR- IntronlO- - GGUGGGGGAGCCCCAUAAAUG 21

2411 21295

CFTR- IntronlO- - GGGUGGGGGAGCCCCAUAAAUG 22

2412 21296

CFTR- IntronlO- - GGGUGAGAUUAGAGGCCACUG 21

2413 21297

CFTR- IntronlO- - GCUUCAGCCUCCCAAAGUG 19

2414 21298

CFTR- IntronlO- - GAACAAAGACUUGCAGGAGGUG 22

2415 21299

CFTR- IntronlO- - GUUUGUUAAAGAAUGACUGUG 21

2416 21300

CFTR- IntronlO- - GGUUUGUUAAAGAAUGACUGUG 22

2417 21301

751

5535.1 CFTR- IntronlO- - GCUAUUAGUAGUUAAGUUUUUG 22

2418 21302

CFTR- IntronlO- - GGCUAUUAGUAGUUAAGUUUUUG 23

2419 21303

CFTR- IntronlO- - GGGAGGUGAUUAGUCCAU 18

2420 21304

CFTR- IntronlO- - GCCUUUGGGAGGUGAUUAGUCCAU 24

2421 21305

CFTR- IntronlO- - GAUGCAUAGUAUUCUAUCAU 20

2422 21306

CFTR- IntronlO- - GAUGAGAAAGAGCUUUCUAGUAU 23

2423 21307

CFTR- IntronlO- - GUCUGUAGGCUAUAUGUAUCU 21

2424 21308

CFTR-

- GCCUCGGCCUCCCAAAGUGU 20

lntronlO-716 19602

CFTR- IntronlO- - GCCUGCCUCGGCCUCCCAAAGUGU 24

2425 21309

CFTR- IntronlO- - GGAAGGCAGUGGUCCCUU 18

2426 21310

CFTR-

- GAGGAAGGCAGUGGUCCCUU 20

lntronlO-127 19013

CFTR- IntronlO- - GAAGCAAGGAGAUGAGUU 18

2427 21311

CFTR- IntronlO- - GGAAGCAAGGAGAUGAGUU 19

2428 21312

CFTR- IntronlO- - GAGGAAGCAAGGAGAUGAGUU 21

2429 21313

CFTR- IntronlO- - GGAGGAAGCAAGGAGAUGAGUU 22

2430 21314

752

5535.1 CFTR- IntronlO- - GGGAGGAAGCAAGGAGAUGAGUU 23

2431 21315

CFTR- IntronlO- - GAAAGAUAAUGGGAGAAACAGGUU 24

2432 21316

CFTR- IntronlO- - GCAUGGGUCCACUUAUUU 18

2433 21317

CFTR- IntronlO- - GAACUGCAUGGGUCCACUUAUUU 23

2434 21318

CFTR- IntronlO- - GCUUUUUUGUUGUUUUUCUAGUUU 24

2435 21319

CFTR- IntronlO- - G U U AAU ACAU UGG AAAAU U U U 21

2436 21320

CFTR- IntronlO- - GUAUGUCCUCCACAAAUAUUUU 22

2437 21321

Table 41D provides exemplary targeting domains for correcting a mutation (e.g., 3272- 26->G) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within intron 10, and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 41D

753

5535.1 2440

CFTR- IntronlO- + CAACAAAAAAG CGAAGAAAAA 21

2441 21325

CFTR- IntronlO- + ACAACAAAAAAGCGAAGAAAAA 22

2442 21326

CFTR- IntronlO- + AACAACAAAAAAG CGAAGAAAAA 23

2443 21327

CFTR- IntronlO- + AAACAACAAAAAAGCGAAGAAAAA 24

2444 21328

CFTR- IntronlO- + AUACAUAUGAUUUUAUGAAAA 21

2445 21329

CFTR- IntronlO- + CAUACAUAUGAUUUUAUGAAAA 22

2446 21330

CFTR- IntronlO- + ACAUACAUAUGAUUUUAUGAAAA 23

2447 21331

CFTR- IntronlO- + UACAUACAUAUGAUUUUAUGAAAA 24

2448 21332

CFTR- IntronlO- + AGAUAAUACUACUGACUAAAA 21

2449 21333

CFTR- IntronlO- + AAGAUAAUACUACUGACUAAAA 22

2450 21334

CFTR- IntronlO- + AAAGAUAAUACUACUGACUAAAA 23

2451 21335

CFTR- IntronlO- + AAAAGAUAAUACUACUGACUAAAA 24

2452 21336

CFTR- IntronlO- + AUAAACAAACAAAGGAAA 18

2453 21337

CFTR-

+ AAUAAACAAACAAAGGAAA 19

IntronlO- 21338

754

5535.1 2454

CFTR- IntronlO- + AAAUAAACAAACAAAGGAAA 20

1097 19982

CFTR- IntronlO- + CAAAUAAACAAACAAAGGAAA 21

2455 21339

CFTR- IntronlO- + CCAAAUAAACAAACAAAGGAAA 22

2456 21340

CFTR- IntronlO- + ACCAAAUAAACAAACAAAGGAAA 23

2457 21341

CFTR- IntronlO- + AACCAAAUAAACAAACAAAGGAAA 24

2458 21342

CFTR- IntronlO- + UAAGACCUAAUCUCUAAA 18

2459 21343

CFTR- IntronlO- + AGUAAGACCUAAUCUCUAAA 20

2460 21344

CFTR- IntronlO- + AGAGUAAGACCUAAUCUCUAAA 22

2461 21345

CFTR- IntronlO- + CAGAGUAAGACCUAAUCUCUAAA 23

2462 21346

CFTR- IntronlO- + ACAGAGUAAGACCUAAUCUCUAAA 24

2463 21347

CFTR- IntronlO- + CAGAUGAGAGACAGUAAAGAA 21

2464 21348

CFTR- IntronlO- + ACAGAUGAGAGACAGUAAAGAA 22

2465 21349

CFTR- IntronlO- + UGUUCUCACAUGGCAGAA 18

2466 21350

CFTR-

+ UGUGUUCUCACAUGGCAGAA 20

IntronlO- 19991

755

5535.1 1106

CFTR- IntronlO- + CUGUGUUCUCACAUGGCAGAA 21

2467 21351

CFTR- IntronlO- + UGCUGUGUUCUCACAUGGCAGAA 23

2468 21352

CFTR- IntronlO- + CUGCUGUGUUCUCACAUGGCAGAA 24

2469 21353

CFTR- IntronlO- + CUUAGGGUGGGAUAUGGAGAA 21

2470 21354

CFTR- IntronlO- + UCUUAGGGUGGGAUAUGGAGAA 22

2471 21355

CFTR- IntronlO- + UUCUUAGGGUGGGAUAUGGAGAA 23

2472 21356

CFTR- IntronlO- + AG G A AG A A A AG U A U C A A U A A 20

1110 19995

CFTR- IntronlO- + C AG G A AG A A A AG U A U C A A U A A 21

2473 21357

CFTR- IntronlO- + U C AG G A AG A A A AG U A U C A A U A A 22

2474 21358

CFTR- IntronlO- + A U C AG G A AG A A A AG U A U C A A U A A 23

2475 21359

CFTR- IntronlO- + AAUCAGGAAGAAAAGUAUCAAUAA 24

2476 21360

CFTR- IntronlO- + AGUUUUUACCAUUAUCUACACA 22

2477 21361

CFTR- IntronlO- + AAGUUUUUACCAUUAUCUACACA 23

2478 21362

CFTR-

+ CAAG U U U U U ACCAU UAU CU ACACA 24

IntronlO- 21363

756

5535.1 2479

CFTR- IntronlO- + AUAUGGAGAAGAGGAUGACCA 21

2480 21364

CFTR- IntronlO- + AAAAGAGACACACCUAAAGCA 21

2481 21365

CFTR- IntronlO- + UAAAAGAGACACACCUAAAGCA 22

2482 21366

CFTR- IntronlO- + CUAAAAGAGACACACCUAAAGCA 23

2483 21367

CFTR- IntronlO- + ACUAAAAGAGACACACCUAAAGCA 24

2484 21368

CFTR- IntronlO- + CAAUAGUGAUUCAUUAUAUCA 21

2485 21369

CFTR- IntronlO- + UCAAUAGUGAUUCAUUAUAUCA 22

2486 21370

CFTR- IntronlO- + AUCAAUAGUGAUUCAUUAUAUCA 23

2487 21371

CFTR- IntronlO- + AAUCAAUAGUGAUUCAUUAUAUCA 24

2488 21372

CFTR- IntronlO- + UUGUAUUUUUAGUAGAGA 18

2489 21373

CFTR- IntronlO- + UUUGUAUUUUUAGUAGAGA 19

2490 21374

CFTR- IntronlO- + UUUUGUAUUUUUAGUAGAGA 20

1141 20026

CFTR- IntronlO- + UUUUUGUAUUUUUAGUAGAGA 21

2491 21375

CFTR-

+ UUUUUUGUAUUUUUAGUAGAGA 22

IntronlO- 21376

757

5535.1 2492

CFTR- IntronlO- + AUUUUUUGUAUUUUUAGUAGAGA 23

2493 21377

CFTR- IntronlO- + AAUUUUUUGUAUUUUUAGUAGAGA 24

2494 21378

CFTR- IntronlO- + UAUUUAUUUAUUUAGAGA 18

2495 21379

CFTR- IntronlO- + UUAUUUAUUUAUUUAGAGA 19

2496 21380

CFTR- IntronlO- + UUUAUUUAUUUAUUUAGAGA 20

2497 21381

CFTR- IntronlO- + AUUUAUUUAUUUAUUUAGAGA 21

2498 21382

CFTR- IntronlO- + UAUUUAUUUAUUUAUUUAGAGA 22

2499 21383

CFTR- IntronlO- + UUAUUUAUUUAUUUAUUUAGAGA 23

2500 21384

CFTR- IntronlO- + UUUAUUUAUUUAUUUAUUUAGAGA 24

2501 21385

CFTR- IntronlO- + ACUAAAAGGCAGCCUCCUAGA 21

2502 21386

CFTR- IntronlO- + UACUAAAAGGCAGCCUCCUAGA 22

2503 21387

CFTR- IntronlO- + CUACUAAAAGGCAGCCUCCUAGA 23

2504 21388

CFTR- IntronlO- + ACUACUAAAAGGCAGCCUCCUAGA 24

2505 21389

CFTR-

+ UGAAGUUCAGCCUGGGUGA 19

IntronlO- 21390

758

5535.1 2506

CFTR- IntronlO- + CUGAAGUUCAGCCUGGGUGA 20

2507 21391

CFTR- IntronlO- + ACUGAAGUUCAGCCUGGGUGA 21

2508 21392

CFTR- IntronlO- + CACUGAAGUUCAGCCUGGGUGA 22

2509 21393

CFTR- IntronlO- + CCACUGAAGUUCAGCCUGGGUGA 23

2510 21394

CFTR- IntronlO- + ACCACUGAAGUUCAGCCUGGGUGA 24

2511 21395

CFTR- IntronlO- + CAAAUUACCAAAUUGUAUUGA 21

2512 21396

CFTR- IntronlO- + ACAAAU U ACCAAAU UG U AU UG A 22

2513 21397

CFTR- IntronlO- + UACAAAUUACCAAAUUGUAUUGA 23

2514 21398

CFTR- IntronlO- + AUACAAAUUACCAAAUUGUAUUGA 24

2515 21399

CFTR- IntronlO- + AGCAAAAAUUACAGAACCUAUA 22

2516 21400

CFTR- IntronlO- + AAGCAAAAAUUACAGAACCUAUA 23

2517 21401

CFTR- IntronlO- + UUUGUUACAACAGUCUUUAUA 21

2518 21402

CFTR- IntronlO- + UUUUGUUACAACAGUCUUUAUA 22

2519 21403

CFTR-

+ CUUUUGUUACAACAGUCUUUAUA 23

IntronlO- 21404

759

5535.1 2520

CFTR- IntronlO- + UCUUUUGUUACAACAGUCUUUAUA 24

2521 21405

CFTR- IntronlO- + UGCUUCCUCCCUUGUCUCCCUA 22

2522 21406

CFTR- IntronlO- + UUGCUUCCUCCCUUGUCUCCCUA 23

2523 21407

CFTR- IntronlO- + CUUGCUUCCUCCCUUGUCUCCCUA 24

2524 21408

CFTR- IntronlO- + CCUUUGUACAUUUUCCUA 18

2525 21409

CFTR- IntronlO- + UCCUUUGUACAUUUUCCUA 19

2526 21410

CFTR- IntronlO- + AUCCUUUGUACAUUUUCCUA 20

2527 21411

CFTR- IntronlO- + AAUCCUUUGUACAUUUUCCUA 21

2528 21412

CFTR- IntronlO- + CAAUCCUUUGUACAUUUUCCUA 22

2529 21413

CFTR- IntronlO- + UCAAUCCUUUGUACAUUUUCCUA 23

2530 21414

CFTR- IntronlO- + UUCAAUCCUUUGUACAUUUUCCUA 24

2531 21415

CFTR- IntronlO- + AG AU AAAAU UAUAAAU U A 18

2532 21416

CFTR- IntronlO- + AAGAUAAAAU UAUAAAU U A 19

2533 21417

CFTR-

+ AAAGAU AAAAU UAUAAAU U A 20

IntronlO- 21418

760

5535.1 2534

CFTR- IntronlO- + U AAAG AU AAAAU U AU AAAU U A 21

2535 21419

CFTR- IntronlO- + AU AAAG AU AAAAU U AU AAAU U A 22

2536 21420

CFTR- IntronlO- + AAU AAAG AU AAAAU U AU AAAU U A 23

2537 21421

CFTR- IntronlO- + U AAU AAAG AU AAAAU U AU AAAU U A 24

2538 21422

CFTR- IntronlO- + UCUCAGACUUUUAUUUUA 18

2539 21423

CFTR- IntronlO- + UUCUCAGACUUUUAUUUUA 19

2540 21424

CFTR- IntronlO- + CUUCUCAGACUUUUAUUUUA 20

2541 21425

CFTR- IntronlO- + UCUUCUCAGACUUUUAUUUUA 21

2542 21426

CFTR- IntronlO- + UGUCUUCUCAGACUUUUAUUUUA 23

2543 21427

CFTR- IntronlO- + UUGUCUUCUCAGACUUUUAUUUUA 24

2544 21428

CFTR- IntronlO- + AGUUUCCAAAUUUUUUUUA 19

2545 21429

CFTR- IntronlO- + AAGUUUCCAAAUUUUUUUUA 20

2546 21430

CFTR- IntronlO- + CAAGUUUCCAAAUUUUUUUUA 21

2547 21431

CFTR-

+ ACAAGUUUCCAAAUUUUUUUUA 22

IntronlO- 21432

761

5535.1 2548

CFTR- IntronlO- + AGACAAGUUUCCAAAUUUUUUUUA 24

2549 21433

CFTR- IntronlO- + UGUGUGGCUUAUAAACAAC 19

2550 21434

CFTR- IntronlO- + CUGUGUGGCUUAUAAACAAC 20

1180 20065

CFTR- IntronlO- + ACUGUGUGGCUUAUAAACAAC 21

2551 21435

CFTR- IntronlO- + AACUGUGUGGCUUAUAAACAAC 22

2552 21436

CFTR- IntronlO- + UGAACUGUGUGGCUUAUAAACAAC 24

2553 21437

CFTR- IntronlO- + UGGGAAGAUACUAAAAAAAGUUAC 24

2554 21438

CFTR- IntronlO- + CGGAAAGGUCAAUUGAGCCC 20

1194 20079

CFTR- IntronlO- + AGCGGAAAGGUCAAUUGAGCCC 22

2555 21439

CFTR- IntronlO- + AAGCGGAAAGGUCAAUUGAGCCC 23

2556 21440

CFTR- IntronlO- + UACUUGGAAGACUCUUCC 18

2557 21441

CFTR- IntronlO- + CUACUUGGAAGACUCUUCC 19

2558 21442

CFTR- IntronlO- + UGCUACUUGGAAGACUCUUCC 21

2559 21443

CFTR-

+ CUGCUACUUGGAAGACUCUUCC 22

IntronlO- 21444

762

5535.1 2560

CFTR- IntronlO- + CCUGCUACUUGGAAGACUCUUCC 23

2561 21445

CFTR- IntronlO- + ACCUGCUACUUGGAAGACUCUUCC 24

2562 21446

CFTR- IntronlO- + ACACCACUGAAGUUCAGC 18

2563 21447

CFTR- IntronlO- + CACACCACUGAAGUUCAGC 19

2564 21448

CFTR- IntronlO- + UCACACCACUGAAGUUCAGC 20

2565 21449

CFTR- IntronlO- + AUCACACCACUGAAGUUCAGC 21

2566 21450

CFTR- IntronlO- + UGAUCACACCACUGAAGUUCAGC 23

2567 21451

CFTR- IntronlO- + AUGAUCACACCACUGAAGUUCAGC 24

2568 21452

CFTR- IntronlO- + CGGAGUUUCACUGUGUUAGC 20

2569 21453

CFTR- IntronlO- + ACGGAGUUUCACUGUGUUAGC 21

2570 21454

CFTR- IntronlO- + AGACGGAGUUUCACUGUGUUAGC 23

2571 21455

CFTR- IntronlO- + UCACUCUGUCACCCAGGC 18

2572 21456

CFTR- IntronlO- + CUCACUCUGUCACCCAGGC 19

2573 21457

CFTR-

+ UCUCACUCUGUCACCCAGGC 20

IntronlO- 21458

763

5535.1 2574

CFTR- IntronlO- + AGUCUCACUCUGUCACCCAGGC 22

2575 21459

CFTR- IntronlO- + AGAGUCUCACUCUGUCACCCAGGC 24

2576 21460

CFTR- IntronlO- + UUUUGAGCCUAUCACCUAGGC 21

2577 21461

CFTR- IntronlO- + UUUUUGAGCCUAUCACCUAGGC 22

2578 21462

CFTR- IntronlO- + UUUUUUGAGCCUAUCACCUAGGC 23

2579 21463

CFTR- IntronlO- + UUUUUUUGAGCCUAUCACCUAGGC 24

2580 21464

CFTR- IntronlO- + CUCUGCCUCCAAAAGUGC 18

2581 21465

CFTR- IntronlO- + CCUCUGCCUCCAAAAGUGC 19

2582 21466

CFTR- IntronlO- + UGCCUCUGCCUCCAAAAGUGC 21

2583 21467

CFTR- IntronlO- + CUGCCUCUGCCUCCAAAAGUGC 22

2584 21468

CFTR- IntronlO- + CCUGCCUCUGCCUCCAAAAGUGC 23

2585 21469

CFTR- IntronlO- + ACCUGCCUCUGCCUCCAAAAGUGC 24

2586 21470

CFTR- IntronlO- + UUCUCCUGCCUCAGCCUC 18

2587 16501

CFTR-

+ AUUCUCCUGCCUCAGCCUC 19

IntronlO- 16502

764

5535.1 2588

CFTR- IntronlO- + CAUUCUCCUGCCUCAGCCUC 20

2589 21471

CFTR- IntronlO- + CCAUUCUCCUGCCUCAGCCUC 21

2590 21472

CFTR- IntronlO- + CGCCAUUCUCCUGCCUCAGCCUC 23

2591 21473

CFTR- IntronlO- + ACGCCAUUCUCCUGCCUCAGCCUC 24

2592 21474

CFTR- IntronlO- + CACUGCAAGUUCUGCCUC 18

2593 21475

CFTR- IntronlO- + UCACUGCAAGUUCUGCCUC 19

2594 21476

CFTR- IntronlO- + CUCACUGCAAGUUCUGCCUC 20

2595 21477

CFTR- IntronlO- + CGGCUCACUGCAAGUUCUGCCUC 23

2596 21478

CFTR- IntronlO- + UCGGCUCACUGCAAGUUCUGCCUC 24

2597 21479

CFTR- IntronlO- + UAUUGCUUUCAUUAAGUC 18

2598 21480

CFTR- IntronlO- + CUAUUGCUUUCAUUAAGUC 19

2599 21481

CFTR- IntronlO- + ACUAUUGCUUUCAUUAAGUC 20

2600 21482

CFTR- IntronlO- + CUUCCUUCAAAGCAUGUC 18

2601 21483

CFTR-

+ UCUUCCUUCAAAGCAUGUC 19

IntronlO- 21484

765

5535.1 2602

CFTR- IntronlO- + AUCUUCCUUCAAAGCAUGUC 20

2603 21485

CFTR- IntronlO- + UGGAUCUUCCUUCAAAGCAUGUC 23

2604 21486

CFTR- IntronlO- + UUGGAUCUUCCUUCAAAGCAUGUC 24

2605 21487

CFTR- IntronlO- + UGAUAUUUUUCAUUAUGAUUC 21

2606 21488

CFTR- IntronlO- + UGGUGAUAUUUUUCAUUAUGAUUC 24

2607 21489

CFTR- IntronlO- + CUUGGGAGGCUGAGGCAG 18

2608 21490

CFTR- IntronlO- + ACUUGGGAGGCUGAGGCAG 19

2609 21491

CFTR- IntronlO- + UACUUGGGAGGCUGAGGCAG 20

2610 21492

CFTR- IntronlO- + CUACUUGGGAGGCUGAGGCAG 21

2611 21493

CFTR- IntronlO- + AGCUACUUGGGAGGCUGAGGCAG 23

2612 21494

CFTR- IntronlO- + CAGCUACUUGGGAGGCUGAGGCAG 24

2613 21495

CFTR- IntronlO- + CUUGGGAGGGUGAGGCAG 18

2614 21496

CFTR- IntronlO- + ACUUGGGAGGGUGAGGCAG 19

2615 21497

CFTR-

+ UACUUGGGAGGGUGAGGCAG 20

IntronlO- 21498

766

5535.1 2616

CFTR- IntronlO- + CUACUUGGGAGGGUGAGGCAG 21

2617 21499

CFTR- IntronlO- + AGCUACUUGGGAGGGUGAGGCAG 23

2618 21500

CFTR- IntronlO- + CAGCUACUUGGGAGGGUGAGGCAG 24

2619 21501

CFTR- IntronlO- + UAAAAAUACAAAAAUUAG 18

2620 21502

CFTR- IntronlO- + CU AAAAAU ACAAAAAU U AG 19

2621 21503

CFTR- IntronlO- + ACU AAAAAU ACAAAAAU U AG 20

2622 21504

CFTR- IntronlO- + U ACU AAAAAU ACAAAAAU U AG 21

2623 21505

CFTR- IntronlO- + CU ACU AAAAAU ACAAAAAU U AG 22

2624 21506

CFTR- IntronlO- + UCUACUAAAAAUACAAAAAUUAG 23

2625 21507

CFTR- IntronlO- + CUCUACUAAAAAUACAAAAAUUAG 24

2626 21508

CFTR- IntronlO- + UGAUCUUGAAGACAUACG 18

2627 21509

CFTR- IntronlO- + UUGAUCUUGAAGACAUACG 19

2628 21510

CFTR- IntronlO- + AUUGAUCUUGAAGACAUACG 20

2629 21511

CFTR-

+ UUGUGUUUUUUGUAGAGG 18

IntronlO- 21512

767

5535.1 2630

CFTR- IntronlO- + UUUGUGUUUUUUGUAGAGG 19

2631 21513

CFTR- IntronlO- + UGUUUGUGUUUUUUGUAGAGG 21

2632 21514

CFTR- IntronlO- + UUGUUUGUGUUUUUUGUAGAGG 22

2633 21515

CFTR- IntronlO- + UUUGUUUGUGUUUUUUGUAGAGG 23

2634 21516

CFTR- IntronlO- + UUUUGUUUGUGUUUUUUGUAGAGG 24

2635 21517

CFTR- IntronlO- + UUUGGGAGGCCGAGGCGG 18

2636 21518

CFTR- IntronlO- + CUUUGGGAGGCCGAGGCGG 19

2637 21519

CFTR- IntronlO- + ACUUUGGGAGGCCGAGGCGG 20

2638 21520

CFTR- IntronlO- + CACUUUGGGAGGCCGAGGCGG 21

2639 21521

CFTR- IntronlO- + AGCACUUUGGGAGGCCGAGGCGG 23

2640 21522

CFTR- IntronlO- + CAGCACUUUGGGAGGCCGAGGCGG 24

2641 21523

CFTR- IntronlO- + AAAAAUUAAAACUAAUGG 18

2642 21524

CFTR- IntronlO- + CAAAAAUUAAAACUAAUGG 19

2643 21525

CFTR-

+ ACAAAAAUUAAAACUAAUGG 20

IntronlO- 21526

768

5535.1 2644

CFTR- IntronlO- + AACAAAAAUUAAAACUAAUGG 21

2645 21527

CFTR- IntronlO- + UGAACAAAAAUUAAAACUAAUGG 23

2646 21528

CFTR- IntronlO- + CUUUAACAAACCUUUUAUUGG 21

2647 21529

CFTR- IntronlO- + UCUUUAACAAACCUUUUAUUGG 22

2648 21530

CFTR- IntronlO- + UUCUUUAACAAACCUUUUAUUGG 23

2649 21531

CFTR- IntronlO- + AUUCUUUAACAAACCUUUUAUUGG 24

2650 21532

CFTR- IntronlO- + UGUAGUCCCAGCUACUUGG 19

2651 21533

CFTR- IntronlO- + CUGUAGUCCCAGCUACUUGG 20

2652 21534

CFTR- IntronlO- + CCUGUAGUCCCAGCUACUUGG 21

2653 21535

CFTR- IntronlO- + UGCCUGUAGUCCCAGCUACUUGG 23

2654 21536

CFTR- IntronlO- + AAAGGAAAUGGGGUAUAAGUG 21

2655 21537

CFTR- IntronlO- + CAAAGGAAAUGGGGUAUAAGUG 22

2656 21538

CFTR- IntronlO- + ACAAAGGAAAUGGGGUAUAAGUG 23

2657 21539

CFTR-

+ AACAAAGGAAAUGGGGUAUAAGUG 24

IntronlO- 21540

769

5535.1 2658

CFTR- IntronlO- + ACUACUAAUAGCCUAUUG 18

2659 21541

CFTR- IntronlO- + AACUACUAAUAGCCUAUUG 19

2660 21542

CFTR- IntronlO- + UAACUACUAAUAGCCUAUUG 20

2661 21543

CFTR- IntronlO- + UUAACUACUAAUAGCCUAUUG 21

2662 21544

CFTR- IntronlO- + CUUAACUACUAAUAGCCUAUUG 22

2663 21545

CFTR- IntronlO- + ACUUAACUACUAAUAGCCUAUUG 23

2664 21546

CFTR- IntronlO- + AACUUAACUACUAAUAGCCUAUUG 24

2665 21547

CFTR- IntronlO- + UAAAACUAAUGGCAGAAU 18

2666 21548

CFTR- IntronlO- + U UAAAACUAAUGGCAGAAU 19

2667 21549

CFTR- IntronlO- + AUUAAAACUAAUGGCAGAAU 20

2668 21550

CFTR- IntronlO- + AAUUAAAACUAAUGGCAGAAU 21

2669 21551

CFTR- IntronlO- + AAAU UAAAACUAAUGGCAGAAU 22

2670 21552

CFTR- IntronlO- + AAAAUUAAAACUAAUGGCAGAAU 23

2671 21553

CFTR-

+ AAAAAUUAAAACUAAUGGCAGAAU 24

IntronlO- 21554

770

5535.1 2672

CFTR- IntronlO- + UACCAUCACCUUGGGAAU 18

2673 21555

CFTR- IntronlO- + AUACCAUCACCUUGGGAAU 19

2674 21556

CFTR- IntronlO- + AAUACCAUCACCUUGGGAAU 20

2675 21557

CFTR- IntronlO- + CAAUACCAUCACCUUGGGAAU 21

2676 21558

CFTR- IntronlO- + UGCAAUACCAUCACCUUGGGAAU 23

2677 21559

CFTR- IntronlO- + CUGCAAUACCAUCACCUUGGGAAU 24

2678 21560

CFTR- IntronlO- + UGGGAAUUAGGAUUUCAACAU 21

2679 21561

CFTR- IntronlO- + UUGGGAAUUAGGAUUUCAACAU 22

2680 21562

CFTR- IntronlO- + CUUGGGAAUUAGGAUUUCAACAU 23

2681 21563

CFTR- IntronlO- + CCUUGGGAAUUAGGAUUUCAACAU 24

2682 21564

CFTR- IntronlO- + AUCAAGGUGCCAGCAGAU 18

2683 21565

CFTR- IntronlO- + AGAUCAAGGUGCCAGCAGAU 20

2684 21566

CFTR- IntronlO- + AAGAUCAAGGUGCCAGCAGAU 21

2685 21567

CFTR-

+ CAAGAUCAAGGUGCCAGCAGAU 22

IntronlO- 21568

771

5535.1 2686

CFTR- IntronlO- + CCAAGAUCAAGGUGCCAGCAGAU 23

2687 21569

CFTR- IntronlO- + UCCAAGAUCAAGGUGCCAGCAGAU 24

2688 21570

CFTR- IntronlO- + UGAUAGUUGCACAACUAU 18

2689 21571

CFTR- IntronlO- + AGGUGAUAGUUGCACAACUAU 21

2690 21572

CFTR- IntronlO- + AGGAGGUGAUAGUUGCACAACUAU 24

2691 21573

CFTR- IntronlO- + UUUACAUUUCUCUUUACU 18

2692 21574

CFTR- IntronlO- + AUUUACAUUUCUCUUUACU 19

2693 21575

CFTR- IntronlO- + UAUUUACAUUUCUCUUUACU 20

2694 21576

CFTR- IntronlO- + UUAUUUACAUUUCUCUUUACU 21

2695 21577

CFTR- IntronlO- + UUUAUUUACAUUUCUCUUUACU 22

2696 21578

CFTR- IntronlO- + UGUUUAUUUACAUUUCUCUUUACU 24

2697 21579

CFTR- IntronlO- + AAAUGUUAAAUUUUCCCU 18

2698 21580

CFTR- IntronlO- + AAAAUGUUAAAUUUUCCCU 19

2699 21581

CFTR-

+ AGUUACUCAGUCCAGAAAGCU 21

IntronlO- 21582

772

5535.1 2700

CFTR- IntronlO- + CAGUUACUCAGUCCAGAAAGCU 22

2701 21583

CFTR- IntronlO- + CCAGUUACUCAGUCCAGAAAGCU 23

2702 21584

CFTR- IntronlO- + U CCAG U U ACU CAG U CCAG AAAG CU 24

2703 21585

CFTR- IntronlO- + AAUUUAAUUGCCAGUAAGUCU 21

2704 21586

CFTR- IntronlO- + AAAU U U AAU UGCCAG UAAG U CU 22

2705 21587

CFTR- IntronlO- + UGAAAUUUAAUUGCCAGUAAGUCU 24

2706 21588

CFTR- IntronlO- + UAUGCCAGGUUAAGUUGUUCU 21

2707 21589

CFTR- IntronlO- + AUAUGCCAGGUUAAGUUGUUCU 22

2708 21590

CFTR- IntronlO- + AAUAUGCCAGGUUAAGUUGUUCU 23

2709 21591

CFTR- IntronlO- + AAAUAUGCCAGGUUAAGUUGUUCU 24

2710 21592

CFTR- IntronlO- + CACAUGGCAGAAAGGGGU 18

2711 21593

CFTR- IntronlO- + UCACAUGGCAGAAAGGGGU 19

2712 21594

CFTR- IntronlO- + CUCACAUGGCAGAAAGGGGU 20

2713 21595

CFTR-

+ UCUCACAUGGCAGAAAGGGGU 21

IntronlO- 21596

773

5535.1 2714

CFTR- IntronlO- + UUCUCACAUGGCAGAAAGGGGU 22

2715 21597

CFTR- IntronlO- + UGUUCUCACAUGGCAGAAAGGGGU 24

2716 21598

CFTR- IntronlO- + UCACUAGUGGCACUUUGU 18

2717 21599

CFTR- IntronlO- + AUCACUAGUGGCACUUUGU 19

2718 21600

CFTR- IntronlO- + CAUCACUAGUGGCACUUUGU 20

2719 21601

CFTR- IntronlO- + UGCAUCACUAGUGGCACUUUGU 22

2720 21602

CFTR- IntronlO- + CGUGCAUCACUAGUGGCACUUUGU 24

2721 21603

CFTR- IntronlO- + CUGCAAUACCAUCACCUU 18

2722 21604

CFTR- IntronlO- + CCUGCAAUACCAUCACCUU 19

2723 21605

CFTR- IntronlO- + CCCUGCAAUACCAUCACCUU 20

1395 20279

CFTR- IntronlO- + ACCCUGCAAUACCAUCACCUU 21

2724 21606

CFTR- IntronlO- + CACCCUGCAAUACCAUCACCUU 22

2725 21607

CFTR- IntronlO- + CCACCCUGCAAUACCAUCACCUU 23

2726 21608

CFTR-

+ CCCACCCUGCAAUACCAUCACCUU 24

IntronlO- 21609

774

5535.1 2727

CFTR- IntronlO- + A U A A A AG A A A U G CAAG U U 18

2728 21610

CFTR- IntronlO- + AAU A A A AG A A A U G CAAG U U 19

2729 21611

CFTR- IntronlO- + U A A U AAAAG AAA U G C A AG U U 20

2730 21612

CFTR- IntronlO- + A U A A U A A A AG A A A U G CAAG U U 21

2731 21613

CFTR- IntronlO- + UAUAAUAAAAGAAAUGCAAGUU 22

2732 21614

CFTR- IntronlO- + U UAU AAU AAAAG AAAUG CAAG U U 23

2733 21615

CFTR- IntronlO- + CU UAU AAU AAAAG AAAUG CAAG U U 24

2734 21616

CFTR- IntronlO- + CCCUUUAUCAACAUGAAGGUU 21

2735 21617

CFTR- IntronlO- + ACCCUUUAUCAACAUGAAGGUU 22

2736 21618

CFTR- IntronlO- + UGACCCUUUAUCAACAUGAAGGUU 24

2737 21619

CFTR- IntronlO- + AUAGAUUUAAUCUUAUUU 18

2738 21620

CFTR- IntronlO- + UAUAGAUUUAAUCUUAUUU 19

2739 21621

CFTR- IntronlO- + AUAUAGAUUUAAUCUUAUUU 20

2740 21622

CFTR-

+ AAUAUAGAUUUAAUCUUAUUU 21

IntronlO- 21623

775

5535.1 2741

CFTR- IntronlO- + AAAUAUAGAUUUAAUCUUAUUU 22

2742 21624

CFTR- IntronlO- + UUCUAGGCUAGACAGUUU 18

2743 21625

CFTR- IntronlO- + UUUCUAGGCUAGACAGUUU 19

2744 21626

CFTR- IntronlO- + AUUUCUAGGCUAGACAGUUU 20

2745 21627

CFTR- IntronlO- + UAUUUCUAGGCUAGACAGUUU 21

2746 21628

CFTR- IntronlO- + CGGUAUUUCUAGGCUAGACAGUUU 24

2747 21629

CFTR- IntronlO- + UUCAAGCCUGUAUUGUUU 18

2748 21630

CFTR- IntronlO- + AGUUCAAGCCUGUAUUGUUU 20

2749 21631

CFTR- IntronlO- + CAGUUCAAGCCUGUAUUGUUU 21

2750 21632

CFTR- IntronlO- + UGCAGUUCAAGCCUGUAUUGUUU 23

2751 21633

CFTR- IntronlO- + AUGCAGUUCAAGCCUGUAUUGUUU 24

2752 21634

CFTR- IntronlO- - UAUUUAAACACUUCUGAGAAA 21

2753 21635

CFTR- IntronlO- - AUAUUUAAACACUUCUGAGAAA 22

2754 21636

CFTR-

- AAU AU U U AAACACU U CUG AG AAA 23

IntronlO- 21637

776

5535.1 2755

CFTR- IntronlO- - AUGCUUUGAAGGAAGAUCCAA 21

2756 21638

CFTR- IntronlO- - CAUGCUUUGAAGGAAGAUCCAA 22

2757 21639

CFTR- IntronlO- - ACAUGCUUUGAAGGAAGAUCCAA 23

2758 21640

CFTR- IntronlO- - AG AACCAU AU U U UG AAG AA 19

2759 21641

CFTR- IntronlO- - UAUAUUAUAGAAAUUUAA 18

2760 21642

CFTR- IntronlO- - AGGUAUAUUAUAGAAAUUUAA 21

2761 21643

CFTR- IntronlO- - CAGGUAUAUUAUAGAAAUUUAA 22

2762 21644

CFTR- IntronlO- - ACAGGUAUAUUAUAGAAAUUUAA 23

2763 21645

CFTR- IntronlO- - UGGAUUUUUGACUAUACA 18

2764 21646

CFTR- IntronlO- - CGUGGAUUUUUGACUAUACA 20

2765 21647

CFTR- IntronlO- - ACGUGGAUUUUUGACUAUACA 21

2766 21648

CFTR- IntronlO- - UACGUGGAUUUUUGACUAUACA 22

2767 21649

CFTR- IntronlO- - AUACGUGGAUUUUUGACUAUACA 23

2768 21650

CFTR-

- UAUACGUGGAUUUUUGACUAUACA 24

IntronlO- 21651

777

5535.1 2769

CFTR- IntronlO- - UCAUUAGGAAAAUGUACA 18

2770 21652

CFTR- IntronlO- - CUCAUUAGGAAAAUGUACA 19

2771 21653

CFTR- IntronlO- - ACUCAUUAGGAAAAUGUACA 20

2772 21654

CFTR- IntronlO- - AGGUCACUGAGGCUGGCA 18

2773 21655

CFTR- IntronlO- - AGGAGGUCACUGAGGCUGGCA 21

2774 21656

CFTR- IntronlO- - AAGGAGGUCACUGAGGCUGGCA 22

2775 21657

CFTR- IntronlO- - UAAGGAGGUCACUGAGGCUGGCA 23

2776 21658

CFTR- IntronlO- - AGAUAUGAAGUUAAAAACAUCA 22

2777 21659

CFTR- IntronlO- - UUAGUAUAGAAUUUUGCAUCA 21

2778 21660

CFTR- IntronlO- - AUUAGUAUAGAAUUUUGCAUCA 22

2779 21661

CFTR- IntronlO- - UAUUAGUAUAGAAUUUUGCAUCA 23

2780 21662

CFTR- IntronlO- - AUAUUAGUAUAGAAUUUUGCAUCA 24

2781 21663

CFTR- IntronlO- - UAAAGAGCCUUUUCUUUUUCA 21

2782 21664

CFTR-

- AUAAAGAGCCUUUUCUUUUUCA 22

IntronlO- 21665

778

5535.1 2783

CFTR- IntronlO- - UAUAAAGAGCCUUUUCUUUUUCA 23

2784 21666

CFTR- IntronlO- - UUAUAAAGAGCCUUUUCUUUUUCA 24

2785 21667

CFTR- IntronlO- - AGAUCUAGCUAAAAUAUAAGA 21

2786 21668

CFTR- IntronlO- - AAGAUCUAGCUAAAAUAUAAGA 22

2787 21669

CFTR- IntronlO- - AAAGAUCUAGCUAAAAUAUAAGA 23

2788 21670

CFTR- IntronlO- - AAAAGAUCUAGCUAAAAUAUAAGA 24

2789 21671

CFTR- IntronlO- - AUUUUUGUAUUUUUAGUAGAGA 22

2790 21672

CFTR- IntronlO- - AAUUUUUGUAUUUUUAGUAGAGA 23

2791 21673

CFTR- IntronlO- - UAAUUUUUGUAUUUUUAGUAGAGA 24

2792 21674

CFTR- IntronlO- - UUACUAUUAUUUUUGAGA 18

2793 21675

CFTR- IntronlO- - AUUACUAUUAUUUUUGAGA 19

2794 21676

CFTR- IntronlO- - UAUUACUAUUAUUUUUGAGA 20

2795 21677

CFTR- IntronlO- - AUAUUACUAUUAUUUUUGAGA 21

2796 21678

CFTR-

- AAUAUUACUAUUAUUUUUGAGA 22

IntronlO- 21679

779

5535.1 2797

CFTR- IntronlO- - UAAUAUUACUAUUAUUUUUGAGA 23

2798 21680

CFTR- IntronlO- - UUAAUAUUACUAUUAUUUUUGAGA 24

2799 21681

CFTR- IntronlO- - UUUUUUUUUUUUUUGAGA 18

2800 21682

CFTR- IntronlO- - UUUUUUUUUUUUUUUGAGA 19

2801 21683

CFTR- IntronlO- - UUUUUUUUUUUUUUUUGAGA 20

1142 20027

CFTR- IntronlO- - UUUUUUUUUUUUUUUUUGAGA 21

2802 21684

CFTR- IntronlO- - UUUUUUUUUUUUUUUUUUGAGA 22

2803 21685

CFTR- IntronlO- - UUUUUUUUUUUUUUUUUUUGAGA 23

2804 21686

CFTR- IntronlO- - UUUUUUUUUUUUUUUUUUUUGAGA 24

2805 21687

CFTR- IntronlO- - UGACCAGAAUGAAAUUAGA 19

2806 21688

CFTR- IntronlO- - UUGACCAGAAUGAAAUUAGA 20

2807 21689

CFTR- IntronlO- - AUUAGGAAAAUGUACAAAGGA 21

2808 21690

CFTR- IntronlO- - CAUUAGGAAAAUGUACAAAGGA 22

2809 21691

CFTR-

- U C A U U AG G A A A A U G U AC A A AG G A 23

IntronlO- 21692

780

5535.1 2810

CFTR- IntronlO- - CUCAUUAGGAAAAUGUACAAAGGA 24

2811 21693

CFTR- IntronlO- - AGAUGAUUCCAAGCUUUCUGGA 22

2812 21694

CFTR- IntronlO- - AAGAUGAUUCCAAGCUUUCUGGA 23

2813 21695

CFTR- IntronlO- - AAAGAUGAUUCCAAGCUUUCUGGA 24

2814 21696

CFTR- IntronlO- - AUAAAUUUAAAGACAUGA 18

2815 21697

CFTR- IntronlO- - AAUAAAU U U AAAG ACAUG A 19

2816 21698

CFTR- IntronlO- - AAAUAAAU U U AAAG ACAUG A 20

2817 21699

CFTR- IntronlO- - AGGAAAUAAAU U U AAAG ACAUG A 23

2818 21700

CFTR- IntronlO- - AGAAGACAAAGCUAGUGA 18

2819 21701

CFTR- IntronlO- - UGAGAAGACAAAGCUAGUGA 20

2820 21702

CFTR- IntronlO- - CUGAGAAGACAAAGCUAGUGA 21

2821 21703

CFTR- IntronlO- - UCUGAGAAGACAAAGCUAGUGA 22

2822 21704

CFTR- IntronlO- - AGUCUGAGAAGACAAAGCUAGUGA 24

2823 21705

CFTR-

- UGCACUCUAGCCUGGGUGA 19

IntronlO- 21706

781

5535.1 2824

CFTR- IntronlO- - CUGCACUCUAGCCUGGGUGA 20

2825 21707

CFTR- IntronlO- - ACUGCACUCUAGCCUGGGUGA 21

2826 21708

CFTR- IntronlO- - CACUGCACUCUAGCCUGGGUGA 22

2827 21709

CFTR- IntronlO- - CCACUGCACUCUAGCCUGGGUGA 23

2828 21710

CFTR- IntronlO- - CCCCUAACCUUCAUGUUGAUA 21

2829 21711

CFTR- IntronlO- - ACCCCUAACCUUCAUGUUGAUA 22

2830 21712

CFTR- IntronlO- - CACCCCUAACCUUCAUGUUGAUA 23

2831 21713

CFTR- IntronlO- - AAAAUACUUUCUAGAAUUAUA 21

2832 21714

CFTR- IntronlO- - CAAAAUACUUUCUAGAAUUAUA 22

2833 21715

CFTR- IntronlO- - UCAAAAUACUUUCUAGAAUUAUA 23

2834 21716

CFTR- IntronlO- - U U CAAAAU ACU U UCUAGAAUUAUA 24

2835 21717

CFTR- IntronlO- - CGUUUUUGCUUGCUUUUUAUA 21

2836 21718

CFTR- IntronlO- - ACGUUUUUGCUUGCUUUUUAUA 22

2837 21719

CFTR-

- CACGUUUUUGCUUGCUUUUUAUA 23

IntronlO- 21720

782

5535.1 2838

CFTR- IntronlO- - UCACGUUUUUGCUUGCUUUUUAUA 24

2839 21721

CFTR- IntronlO- - CUUGCAGGAGGUGAGGGAUUA 21

2840 21722

CFTR- IntronlO- - ACUUGCAGGAGGUGAGGGAUUA 22

2841 21723

CFTR- IntronlO- - AGACUUGCAGGAGGUGAGGGAUUA 24

2842 21724

CFTR- IntronlO- - CCAAUAAAAGGUUUGUUA 18

2843 21725

CFTR- IntronlO- - AGCCAAUAAAAGGUUUGUUA 20

2844 21726

CFTR- IntronlO- - UAAGUUAGCAAUGGUCUAAAC 21

2845 21727

CFTR- IntronlO- - AUAAGUUAGCAAUGGUCUAAAC 22

2846 21728

CFTR- IntronlO- - AAU AAG U U AGCAAUGG U CU AAAC 23

2847 21729

CFTR- IntronlO- - AAAUAAGUUAGCAAUGGUCUAAAC 24

2848 21730

CFTR- IntronlO- - UAAACUUUGUUUUUCAAC 18

2849 21731

CFTR- IntronlO- - UUAAACUUUGUUUUUCAAC 19

2850 21732

CFTR- IntronlO- - UUUAAACUUUGUUUUUCAAC 20

2851 21733

CFTR-

- AUUUAAACUUUGUUUUUCAAC 21

IntronlO- 21734

783

5535.1 2852

CFTR- IntronlO- - UAUUUAAACUUUGUUUUUCAAC 22

2853 21735

CFTR- IntronlO- - AUAUUUAAACUUUGUUUUUCAAC 23

2854 21736

CFTR- IntronlO- - CAUAUUUAAACUUUGUUUUUCAAC 24

2855 21737

CFTR- IntronlO- - CAUAUAUAUAUUUUUAAC 18

2856 21738

CFTR- IntronlO- - UGCAUAUAUAUAUUUUUAAC 20

2857 21739

CFTR- IntronlO- - AUGCAUAUAUAUAUUUUUAAC 21

2858 21740

CFTR- IntronlO- - UAUGCAUAUAUAUAUUUUUAAC 22

2859 21741

CFTR- IntronlO- - AUAUGCAUAUAUAUAUUUUUAAC 23

2860 21742

CFTR- IntronlO- - AAUAUGCAUAUAUAUAUUUUUAAC 24

2861 21743

CFTR- IntronlO- - UGGAGUCAAAAAUUAUAC 18

2862 21744

CFTR- IntronlO- - UGUGGAGUCAAAAAUUAUAC 20

2863 21745

CFTR- IntronlO- - UUGUGGAGUCAAAAAUUAUAC 21

2864 21746

CFTR- IntronlO- - UUUGUGGAGUCAAAAAUUAUAC 22

2865 21747

CFTR-

- UU UUGUGGAGUCAAAAAUUAUAC 23

IntronlO- 21748

784

5535.1 2866

CFTR- IntronlO- - UUUUUGUGGAGUCAAAAAUUAUAC 24

2867 21749

CFTR- IntronlO- - AGUGCAAUGCCAUAAACC 18

2868 21750

CFTR- IntronlO- - UAGUGCAAUGCCAUAAACC 19

2869 21751

CFTR- IntronlO- - UUAGUGCAAUGCCAUAAACC 20

2870 21752

CFTR- IntronlO- - UUUAGUGCAAUGCCAUAAACC 21

2871 21753

CFTR- IntronlO- - UGUUUAGUGCAAUGCCAUAAACC 23

2872 21754

CFTR- IntronlO- - AUGUUUAGUGCAAUGCCAUAAACC 24

2873 21755

CFTR- IntronlO- - AGAAAAAGUAAGAUAUGCC 19

2874 21756

CFTR- IntronlO- - A AG A A A A AG UAAGAUAUGCC 20

2875 21757

CFTR- IntronlO- - UAAGAAAAAGUAAGAUAUGCC 21

2876 21758

CFTR- IntronlO- - UUAAGAAAAAGUAAGAUAUGCC 22

2877 21759

CFTR- IntronlO- - AUUAAGAAAAAGUAAGAUAUGCC 23

2878 21760

CFTR- IntronlO- - AAUUAAGAAAAAGUAAGAUAUGCC 24

2879 21761

CFTR-

- AGGUGAAUUGCUUGAGUCC 19

IntronlO- 21762

785

5535.1 2880

CFTR- IntronlO- - CAGGUGAAUUGCUUGAGUCC 20

1217 20102

CFTR- IntronlO- - AGGCAGGUGAAUUGCUUGAGUCC 23

2881 21763

CFTR- IntronlO- - CUAAAACCAAACAAGCUUUCC 21

2882 21764

CFTR- IntronlO- - ACU AAAACC AAACAAG C U U U CC 22

2883 21765

CFTR- IntronlO- - UACUAAAACCAAACAAGCUUUCC 23

2884 21766

CFTR- IntronlO- - CUACUAAAACCAAACAAGCUUUCC 24

2885 21767

CFTR- IntronlO- - AAAUUUUCUUUGUUUUCC 18

2886 21768

CFTR- IntronlO- - CAAAUUUUCUUUGUUUUCC 19

2887 21769

CFTR- IntronlO- - ACAAAUUUUCUUUGUUUUCC 20

2888 21770

CFTR- IntronlO- - AACAAAUUUUCUUUGUUUUCC 21

2889 21771

CFTR- IntronlO- - AAACAAAUUUUCUUUGUUUUCC 22

2890 21772

CFTR- IntronlO- - AAAACAAAUUUUCUUUGUUUUCC 23

2891 21773

CFTR- IntronlO- - CAGCUUUU A A A AC A A A A U AG C 21

2892 21774

CFTR-

- ACAGCUUUUAAAACAAAAUAGC 22

IntronlO- 21775

786

5535.1 2893

CFTR- IntronlO- - AACAG CU U U U AAAACAAAAU AG C 23

2894 21776

CFTR- IntronlO- - AAACAGCUUUUAAAACAAAAUAGC 24

2895 21777

CFTR- IntronlO- - CGCGCCACUGCACUCUAGC 19

2896 21778

CFTR- IntronlO- - UCGCGCCACUGCACUCUAGC 20

2897 21779

CFTR- IntronlO- - AUCGCGCCACUGCACUCUAGC 21

2898 21780

CFTR- IntronlO- - AGAUCGCGCCACUGCACUCUAGC 23

2899 21781

CFTR- IntronlO- - CGGGGUUUCACCGUUUUAGC 20

1224 20109

CFTR- IntronlO- - ACGGGGUUUCACCGUUUUAGC 21

2900 21782

CFTR- IntronlO- - AGACGGGGUUUCACCGUUUUAGC 23

2901 21783

CFTR- IntronlO- - UCGCUCUGUCGCCCAGGC 18

2902 21784

CFTR- IntronlO- - CUCGCUCUGUCGCCCAGGC 19

2903 21785

CFTR- IntronlO- - UCUCGCUCUGUCGCCCAGGC 20

1226 20111

CFTR- IntronlO- - AGUCUCGCUCUGUCGCCCAGGC 22

2904 21786

CFTR-

- CGGGGUUUCACCAUGUUGGC 20

IntronlO- 21787

787

5535.1 2905

CFTR- IntronlO- - ACGGGGUUUCACCAUGUUGGC 21

2906 21788

CFTR- IntronlO- - AGACGGGGUUUCACCAUGUUGGC 23

2907 21789

CFTR- IntronlO- - AAUACAGGCUUGAACUGC 18

2908 21790

CFTR- IntronlO- - CAAUACAGGCUUGAACUGC 19

2909 21791

CFTR- IntronlO- - ACAAUACAGGCUUGAACUGC 20

2910 21792

CFTR- IntronlO- - AACAAUACAGGCUUGAACUGC 21

2911 21793

CFTR- IntronlO- - AAACAAUACAGGCUUGAACUGC 22

2912 21794

CFTR- IntronlO- - UAAACAAUACAGGCUUGAACUGC 23

2913 21795

CFTR- IntronlO- - UUAAACAAUACAGGCUUGAACUGC 24

2914 21796

CFTR- IntronlO- - CUCGGCCUCCCAAAGUGC 18

2915 21797

CFTR- IntronlO- - CCUCGGCCUCCCAAAGUGC 19

2916 21798

CFTR- IntronlO- - CGCCUCGGCCUCCCAAAGUGC 21

2917 21799

CFTR- IntronlO- - CCGCCUCGGCCUCCCAAAGUGC 22

2918 21800

CFTR-

- CCCGCCUCGGCCUCCCAAAGUGC 23

IntronlO- 21801

788

5535.1 2919

CFTR- IntronlO- - CAGAGGCAGGUGAAUUGC 18

2920 21802

CFTR- IntronlO- - AGGCAGAGGCAGGUGAAUUGC 21

2921 21803

CFTR- IntronlO- - UGGAGGCAGAGGCAGGUGAAUUGC 24

2922 21804

CFTR- IntronlO- - CACUGCAAGCUCCGCCUC 18

2923 21805

CFTR- IntronlO- - UCACUGCAAGCUCCGCCUC 19

2924 21806

CFTR- IntronlO- - CUCACUGCAAGCUCCGCCUC 20

2925 21807

CFTR- IntronlO- - CGGCUCACUGCAAGCUCCGCCUC 23

2926 21808

CFTR- IntronlO- - UCGGCUCACUGCAAGCUCCGCCUC 24

2927 21809

CFTR- IntronlO- - AGGUUCUGUAAUUUUUGCUUC 21

2928 21810

CFTR- IntronlO- - UAGGUUCUGUAAUUUUUGCUUC 22

2929 21811

CFTR- IntronlO- - AUAGGUUCUGUAAUUUUUGCUUC 23

2930 21812

CFTR- IntronlO- - UAUAGGUUCUGUAAUUUUUGCUUC 24

2931 21813

CFTR- IntronlO- - UGUAACAGUACAAGAAAAAAG 21

2932 21814

CFTR-

- U U G U AACAG U ACAAG AAAAAAG 22

IntronlO- 21815

789

5535.1 2933

CFTR- IntronlO- - AG U UG U AACAG U ACAAG AAAAAAG 24

2934 21816

CFTR- IntronlO- - CUUUGCCAUUAACAGAUAAAG 21

2935 21817

CFTR- IntronlO- - UGCUUUGCCAUUAACAGAUAAAG 23

2936 21818

CFTR- IntronlO- - UUGCUUUGCCAUUAACAGAUAAAG 24

2937 21819

CFTR- IntronlO- - UUUUGGAGGCAGAGGCAG 18

2938 21820

CFTR- IntronlO- - CUUUUGGAGGCAGAGGCAG 19

2939 21821

CFTR- IntronlO- - ACUUUUGGAGGCAGAGGCAG 20

2940 21822

CFTR- IntronlO- - CACUUUUGGAGGCAGAGGCAG 21

2941 21823

CFTR- IntronlO- - AGCACUUUUGGAGGCAGAGGCAG 23

2942 21824

CFTR- IntronlO- - UAGCACUUUUGGAGGCAGAGGCAG 24

2943 21825

CFTR- IntronlO- - CUCGGGAGGCUGAGGCAG 18

2944 21826

CFTR- IntronlO- - ACUCGGGAGGCUGAGGCAG 19

2945 21827

CFTR- IntronlO- - UACUCGGGAGGCUGAGGCAG 20

2946 21828

CFTR-

- CUACUCGGGAGGCUGAGGCAG 21

IntronlO- 21829

790

5535.1 2947

CFTR- IntronlO- - AGCUACUCGGGAGGCUGAGGCAG 23

2948 21830

CFTR- IntronlO- - CAGCUACUCGGGAGGCUGAGGCAG 24

2949 21831

CFTR- IntronlO- - AAGGGAGGAAGCAAGGAG 18

2950 21832

CFTR- IntronlO- - CAAGG G AG G AAG CAAG G AG 19

2951 21833

CFTR- IntronlO- - ACAAGGGAGGAAGCAAGGAG 20

2952 21834

CFTR- IntronlO- - AGACAAGGGAGGAAGCAAGGAG 22

2953 21835

CFTR- IntronlO- - ACAAACAAAAGAAAAUAG 18

2954 21836

CFTR- IntronlO- - CACAAACAAAAGAAAAUAG 19

2955 21837

CFTR- IntronlO- - ACACAAACAAAAGAAAAUAG 20

2956 21838

CFTR- IntronlO- - AACACAAACAAAAGAAAAUAG 21

2957 21839

CFTR- IntronlO- - AAACACAAACAAAAGAAAAUAG 22

2958 21840

CFTR- IntronlO- - AAAACACAAACAAAAGAAAAUAG 23

2959 21841

CFTR- IntronlO- - AAAAACACAAACAAAAGAAAAUAG 24

2960 21842

CFTR-

- U CCAAAU AG AG AUG U U AG 18

IntronlO- 21843

791

5535.1 2961

CFTR- IntronlO- - AUCCAAAUAGAGAUGUUAG 19

2962 21844

CFTR- IntronlO- - CAUCCAAAUAGAGAUGUUAG 20

2963 21845

CFTR- IntronlO- - ACAU CCAAAU AG AG AUG U U AG 21

2964 21846

CFTR- IntronlO- - UGACAUCCAAAUAGAGAUGUUAG 23

2965 21847

CFTR- IntronlO- - UUGACAUCCAAAUAGAGAUGUUAG 24

2966 21848

CFTR- IntronlO- - AGAGUAAGACAGGGAGGG 18

2967 21849

CFTR- IntronlO- - UAGAGUAAGACAGGGAGGG 19

2968 21850

CFTR- IntronlO- - AUAGAGUAAGACAGGGAGGG 20

2969 21851

CFTR- IntronlO- - CAUAGAGUAAGACAGGGAGGG 21

2970 21852

CFTR- IntronlO- - UGGCAUAGAGUAAGACAGGGAGGG 24

2971 21853

CFTR- IntronlO- - UAGUAUUCUAUCAUAUGG 18

2972 21854

CFTR- IntronlO- - AUAGUAUUCUAUCAUAUGG 19

2973 21855

CFTR- IntronlO- - CAUAGUAUUCUAUCAUAUGG 20

2974 21856

CFTR-

- UGCAUAGUAUUCUAUCAUAUGG 22

IntronlO- 21857

792

5535.1 2975

CFTR- IntronlO- - AUGCAUAGUAUUCUAUCAUAUGG 23

2976 21858

CFTR- IntronlO- - UCUGGACUGAGUAACUGG 18

2977 21859

CFTR- IntronlO- - UUCUGGACUGAGUAACUGG 19

2978 21860

CFTR- IntronlO- - UUUCUGGACUGAGUAACUGG 20

2979 21861

CFTR- IntronlO- - CUUUCUGGACUGAGUAACUGG 21

2980 21862

CFTR- IntronlO- - AGCUUUCUGGACUGAGUAACUGG 23

2981 21863

CFTR- IntronlO- - AAGCUUUCUGGACUGAGUAACUGG 24

2982 21864

CFTR- IntronlO- - UGUAUAUAUGUGUGUCUGG 19

2983 21865

CFTR- IntronlO- - AUGUAUAUAUGUGUGUCUGG 20

2984 21866

CFTR- IntronlO- - UAUGUAUAUAUGUGUGUCUGG 21

2985 21867

CFTR- IntronlO- - UGUAUGUAUAUAUGUGUGUCUGG 23

2986 21868

CFTR- IntronlO- - AUGUAUGUAUAUAUGUGUGUCUGG 24

2987 21869

CFTR- IntronlO- - CAGGCUGGAGUGCAGUGG 18

2988 21870

CFTR-

- CCAGGCUGGAGUGCAGUGG 19

IntronlO- 21871

793

5535.1 2989

CFTR- IntronlO- - CCCAGGCUGGAGUGCAGUGG 20

1304 20189

CFTR- IntronlO- - CGCCCAGGCUGGAGUGCAGUGG 22

2990 21872

CFTR- IntronlO- - UCGCCCAGGCUGGAGUGCAGUGG 23

2991 21873

CFTR- IntronlO- - CUUGGGAGGCUGAGGUGG 18

2992 21874

CFTR- IntronlO- - ACUUGGGAGGCUGAGGUGG 19

2993 21875

CFTR- IntronlO- - UACUUGGGAGGCUGAGGUGG 20

2994 21876

CFTR- IntronlO- - CUACUUGGGAGGCUGAGGUGG 21

2995 21877

CFTR- IntronlO- - AGCUACUUGGGAGGCUGAGGUGG 23

2996 21878

CFTR- IntronlO- - CAGCUACUUGGGAGGCUGAGGUGG 24

2997 21879

CFTR- IntronlO- - UGGGUGGGGGAGCCCCAUAAAUG 23

2998 21880

CFTR- IntronlO- - UUGGGUGGGGGAGCCCCAUAAAUG 24

2999 21881

CFTR- IntronlO- - AAUUAGCCAGACGUGAUG 18

3000 21882

CFTR- IntronlO- - AAAUUAGCCAGACGUGAUG 19

3001 21883

CFTR-

- AAAAUUAGCCAGACGUGAUG 20

IntronlO- 21884

794

5535.1 3002

CFTR- IntronlO- - AAAAAUUAGCCAGACGUGAUG 21

3003 21885

CFTR- IntronlO- - A A A A A A UUAGCCAGACGUGAUG 22

3004 21886

CFTR- IntronlO- - C A A A A A A UUAGCCAGACGUGAUG 23

3005 21887

CFTR- IntronlO- - ACAAAAAAUUAGCCAGACGUGAUG 24

3006 21888

CFTR- IntronlO- - UGGGUGAGAUUAGAGGCCACUG 22

3007 21889

CFTR- IntronlO- - CUGGGUGAGAUUAGAGGCCACUG 23

3008 21890

CFTR- IntronlO- - UCUGGGUGAGAUUAGAGGCCACUG 24

3009 21891

CFTR- IntronlO- - CUUCAGCCUCCCAAAGUG 18

3010 21892

CFTR- IntronlO- - CGCUUCAGCCUCCCAAAGUG 20

3011 21893

CFTR- IntronlO- - CCGCUUCAGCCUCCCAAAGUG 21

3012 21894

CFTR- IntronlO- - UCCGCUUCAGCCUCCCAAAGUG 22

3013 21895

CFTR- IntronlO- - UUCCGCUUCAGCCUCCCAAAGUG 23

3014 21896

CFTR- IntronlO- - UUUCCGCUUCAGCCUCCCAAAGUG 24

3015 21897

CFTR-

- AAAGACUUGCAGGAGGUG 18

IntronlO- 21898

795

5535.1 3016

CFTR- IntronlO- - CAAAGACUUGCAGGAGGUG 19

3017 21899

CFTR- IntronlO- - ACAAAGACUUGCAGGAGGUG 20

1317 20202

CFTR- IntronlO- - AACAAAGACUUGCAGGAGGUG 21

3018 21900

CFTR- IntronlO- - UGAA CAAAGACUUGCAGGAGGUG 23

3019 21901

CFTR- IntronlO- - UUGAACAAAGACUUGCAGGAGGUG 24

3020 21902

CFTR- IntronlO- - AGGUUUGUUAAAGAAUGACUGUG 23

3021 21903

CFTR- IntronlO- - AAGGUUUGUUAAAGAAUGACUGUG 24

3022 21904

CFTR- IntronlO- - CCCAAGGUGAUGGUAUUG 18

3023 21905

CFTR- IntronlO- - UCCCAAGGUGAUGGUAUUG 19

3024 21906

CFTR- IntronlO- - UUCCCAAGGUGAUGGUAUUG 20

3025 21907

CFTR- IntronlO- - AUUCCCAAGGUGAUGGUAUUG 21

3026 21908

CFTR- IntronlO- - AAUUCCCAAGGUGAUGGUAUUG 22

3027 21909

CFTR- IntronlO- - UAAUUCCCAAGGUGAUGGUAUUG 23

3028 21910

CFTR-

- CUAAUUCCCAAGGUGAUGGUAUUG 24

IntronlO- 21911

796

5535.1 3029

CFTR- IntronlO- - UUAGUAGUUAAGUUUUUG 18

3030 21912

CFTR- IntronlO- - AUUAGUAGUUAAGUUUUUG 19

3031 21913

CFTR- IntronlO- - UAUUAGUAGUUAAGUUUUUG 20

1325 20210

CFTR- IntronlO- - CUAUUAGUAGUUAAGUUUUUG 21

3032 21914

CFTR- IntronlO- - AGGCUAUUAGUAGUUAAGUUUUUG 24

3033 21915

CFTR- IntronlO- - UCAGAUUUUUUCCCAUGUAAU 21

3034 21916

CFTR- IntronlO- - UUCAGAUUUUUUCCCAUGUAAU 22

3035 21917

CFTR- IntronlO- - AUUCAGAUUUUUUCCCAUGUAAU 23

3036 21918

CFTR- IntronlO- - AAUUCAGAUUUUUUCCCAUGUAAU 24

3037 21919

CFTR- IntronlO- - UGGGAGGUGAUUAGUCCAU 19

3038 21920

CFTR- IntronlO- - UUGGGAGGUGAUUAGUCCAU 20

3039 21921

CFTR- IntronlO- - UUUGGGAGGUGAUUAGUCCAU 21

3040 21922

CFTR- IntronlO- - CUUUGGGAGGUGAUUAGUCCAU 22

3041 21923

CFTR-

- CCUUUGGGAGGUGAUUAGUCCAU 23

IntronlO- 21924

797

5535.1 3042

CFTR- IntronlO- - UGCAUAGUAUUCUAUCAU 18

3043 21925

CFTR- IntronlO- - AUGCAUAGUAUUCUAUCAU 19

3044 21926

CFTR- IntronlO- - AGAUGCAUAGUAUUCUAUCAU 21

3045 21927

CFTR- IntronlO- - UAGAUGCAUAGUAUUCUAUCAU 22

3046 21928

CFTR- IntronlO- - AUAGAUGCAUAGUAUUCUAUCAU 23

3047 21929

CFTR- IntronlO- - AAUAGAUGCAUAGUAUUCUAUCAU 24

3048 21930

CFTR- IntronlO- - UGAGAAAGAGCUUUCUAGUAU 21

3049 21931

CFTR- IntronlO- - AUGAGAAAGAGCUUUCUAGUAU 22

3050 21932

CFTR- IntronlO- - AGAUGAGAAAGAGCUUUCUAGUAU 24

3051 21933

CFTR- IntronlO- - UAAAAAGCUGUGCAUUUUCCU 21

3052 21934

CFTR- IntronlO- - UUAAAAAGCUGUGCAUUUUCCU 22

3053 21935

CFTR- IntronlO- - UUUAAAAAGCUGUGCAUUUUCCU 23

3054 21936

CFTR- IntronlO- - UUUUAAAAAGCUGUGCAUUUUCCU 24

3055 21937

CFTR-

- CAAAUUAUUUCUACUGCU 18

IntronlO- 21938

798

5535.1 3056

CFTR- IntronlO- - UCAAAUUAUUUCUACUGCU 19

3057 21939

CFTR-

- UUCAAAUUAUUUCUACUGCU 20

lntronlO-521 19407

CFTR- IntronlO- - UGUCUGUAGGCUAUAUGUAUCU 22

3058 21940

CFTR- IntronlO- - UUGUCUGUAGGCUAUAUGUAUCU 23

3059 21941

CFTR- IntronlO- - AUUGUCUGUAGGCUAUAUGUAUCU 24

3060 21942

CFTR- IntronlO- - CUCGGCCUCCCAAAGUGU 18

3061 21943

CFTR- IntronlO- - CCUCGGCCUCCCAAAGUGU 19

3062 21944

CFTR- IntronlO- - UGCCUCGGCCUCCCAAAGUGU 21

3063 21945

CFTR- IntronlO- - CUGCCUCGGCCUCCCAAAGUGU 22

3064 21946

CFTR- IntronlO- - CCUGCCUCGGCCUCCCAAAGUGU 23

3065 21947

CFTR- IntronlO- - AGGAAGGCAGUGGUCCCUU 19

3066 21948

CFTR- IntronlO- - AGGAAGCAAGGAGAUGAGUU 20

1399 20283

CFTR- IntronlO- - AGGGAGGAAGCAAGGAGAUGAGUU 24

3067 21949

CFTR- IntronlO- - AGAUAAUGGGAGAAACAGGUU 21

3068 21950

799

5535.1 CFTR- IntronlO- - AAGAUAAUGGGAGAAACAGGUU 22

3069 21951

CFTR- IntronlO- - AAAGAUAAUGGGAGAAACAGGUU 23

3070 21952

CFTR- IntronlO- - AUAGUUUUAUCAAUAUUU 18

3071 21953

CFTR- IntronlO- - AAUAGUUUUAUCAAUAUUU 19

3072 21954

CFTR- IntronlO- - AAAU AG UUUUAUCAAUAUUU 20

1405 20289

CFTR- IntronlO- - UGCAUGGGUCCACUUAUUU 19

3073 21955

CFTR- IntronlO- - CUGCAUGGGUCCACUUAUUU 20

3074 21956

CFTR- IntronlO- - ACUGCAUGGGUCCACUUAUUU 21

3075 21957

CFTR- IntronlO- - AACUGCAUGGGUCCACUUAUUU 22

3076 21958

CFTR- IntronlO- - UGAACUGCAUGGGUCCACUUAUUU 24

3077 21959

CFTR- IntronlO- - UUGUUGUUUUUCUAGUUU 18

3078 21960

CFTR- IntronlO- - UUUGUUGUUUUUCUAGUUU 19

3079 21961

CFTR- IntronlO- - UUUUGUUGUUUUUCUAGUUU 20

3080 21962

CFTR- IntronlO- - UUUUUGUUGUUUUUCUAGUUU 21

3081 21963

800

5535.1 CFTR- IntronlO- - UUUUUUGUUGUUUUUCUAGUUU 22

3082 21964

CFTR- IntronlO- - CUUUUUUGUUGUUUUUCUAGUUU 23

3083 21965

CFTR- IntronlO- - AAUACAUUGGAAAAUUUU 18

3084 21966

CFTR- IntronlO- - UAAUACAUUGGAAAAUUUU 19

3085 21967

CFTR- IntronlO- - U U AAU ACAU UGG AAAAU U U U 20

1411 20295

CFTR- IntronlO- - AG U U AAU ACAU UGG AAAAU U U U 22

3086 21968

CFTR- IntronlO- - CAGU UAAUACAUUGGAAAAUUUU 23

3087 21969

CFTR- IntronlO- - U CAG U U AAU ACAU UGG AAAAU U U U 24

3088 21970

CFTR- IntronlO- - UAUGUCCUCCACAAAUAUUUU 21

3089 21971

CFTR- IntronlO- - AGUAUGUCCUCCACAAAUAUUUU 23

3090 21972

CFTR- IntronlO- - AAGUAUGUCCUCCACAAAUAUUUU 24

3091 21973

Table 41E provides exemplary targeting domains for correcting a mutation (e.g., 3272- 26->G) in the CFTR gene selected according to the fifth tier parameters. The targeting domains bind within intron 10, and PAM is NNGRRV. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 41E

801

5535.1 5th Tier

Target Site

gRNA Name DNA Strand Targeting Domain

Length Seq ID

CFTR- IntronlO- + AAAAAAAAAAAAAAAAAA 18

3092 21974

CFTR- IntronlO- + AAAAAAAAAAAAAAAAAAA 19

3093 21975

CFTR- IntronlO- + AAAAAAAAAAAAAAAAAAAA 20

3094 21976

CFTR- IntronlO- + AAAAAAAAAAAAAAAAAAAAA 21

3095 21977

CFTR- IntronlO- + AAAAAAAAAAAAAAAAAAAAAA 22

3096 21978

CFTR- IntronlO- + AAAAAAAAAAAAAAAAAAAAAAA 23

3097 21979

CFTR- IntronlO- + CAAAAAAAAAAAAAAAAAAAAAAA 24

3098 21980

CFTR- IntronlO- + U AG AAAAAC AACAAAAAA 18

3099 21981

CFTR- IntronlO- + CUAGAAAAACAACAAAAAA 19

3100 21982

CFTR- IntronlO- + ACUAGAAAAACAACAAAAAA 20

3101 21983

CFTR- IntronlO- + AACUAGAAAAACAACAAAAAA 21

3102 21984

CFTR- IntronlO- + AAACUAGAAAAACAACAAAAAA 22

3103 21985

CFTR- IntronlO- + AAAACUAGAAAAACAACAAAAAA 23

3104 21986

802

5535.1 CFTR- IntronlO- + AAAAACUAGAAAAACAACAAAAAA 24

3105 21987

CFTR- IntronlO- + CAAACAAAGAAACAAAAA 18

3106 21988

CFTR- IntronlO- + ACAAACAAAGAAACAAAAA 19

3107 21989

CFTR- IntronlO- + U ACAAAC AAAG AAAC AAAAA 20

3108 21990

CFTR- IntronlO- + AUACAAACAAAGAAACAAAAA 21

3109 21991

CFTR- IntronlO- + AAUACAAACAAAGAAACAAAAA 22

3110 21992

CFTR- IntronlO- + AAAUACAAACAAAGAAACAAAAA 23

3111 21993

CFTR- IntronlO- + UAAAUACAAACAAAGAAACAAAAA 24

3112 21994

CFTR- IntronlO- + CAU AU UG U U ACAU AAAAA 18

3113 21995

CFTR- IntronlO- + GCAUAUUGUUACAUAAAAA 19

3114 21996

CFTR- IntronlO- + UGCAUAUUGUUACAUAAAAA 20

3115 21997

CFTR- IntronlO- + CUGCAUAUUGUUACAUAAAAA 21

3116 21998

CFTR- IntronlO- + UCUGCAUAUUGUUACAUAAAAA 22

3117 21999

CFTR- IntronlO- + CUCUGCAUAUUGUUACAUAAAAA 23

3118 22000

803

5535.1 CFTR- IntronlO- + ACUCUGCAUAUUGUUACAUAAAAA 24

3119 22001

CFTR- IntronlO- + G U G C A U A A AG G U U G A A A A 18

3120 22002

CFTR- IntronlO- + AGUGCAUAAAGGUUGAAAA 19

3121 22003

CFTR-

+ GAGUGCAUAAAGGUUGAAAA 20

lntronlO-65 18951

CFTR- IntronlO- + AGAGUGCAUAAAGGUUGAAAA 21

3122 22004

CFTR- IntronlO- + A AG AG U G C A U A A AG G U U G A A A A 22

3123 22005

CFTR- IntronlO- + AAAGAGUGCAU A A AG G U U G A A A A 23

3124 22006

CFTR- IntronlO- + CAAAGAGUGCAUAAAGGUUGAAAA 24

3125 22007

CFTR- IntronlO- + U U U CCU CAAU AG U UAAAA 18

3126 22008

CFTR- IntronlO- + AUUUCCUCAAUAGUUAAAA 19

3127 22009

CFTR- IntronlO- + UAUUUCCUCAAUAGUUAAAA 20

3128 22010

CFTR- IntronlO- + UUAUUUCCUCAAUAGUUAAAA 21

3129 22011

CFTR- IntronlO- + UUUAUUUCCUCAAUAGUUAAAA 22

3130 22012

CFTR- IntronlO- + AUUUAUUUCCUCAAUAGUUAAAA 23

3131 22013

CFTR-

+ AAUUUAUUUCCUCAAUAGUUAAAA 24

IntronlO- 22014

804

5535.1 3132

CFTR- IntronlO- + UAGU AAAAAAAAAU CAAA 18

3133 22015

CFTR- IntronlO- + U U AG U AAAAAAAAAU CAAA 19

3134 22016

CFTR- IntronlO- + A U U AG U A A A A A A A A A U CAAA 20

1092 19977

CFTR- IntronlO- + AAU U AG U A A A A A A A A A U CAAA 21

3135 22017

CFTR- IntronlO- + AAAU UAGU AAAAAAAAAU CAAA 22

3136 22018

CFTR- IntronlO- + AAAAU U AG U AAAAAAAAAU CAAA 23

3137 22019

CFTR- IntronlO- + CAAAAUUAGUAAAAAAAAAUCAAA 24

3138 22020

CFTR- IntronlO- + GCUAAAAUGACAAUCAAA 18

3139 22021

CFTR- IntronlO- + AGCUAAAAUGACAAUCAAA 19

3140 22022

CFTR-

+ CAGCUAAAAUGACAAUCAAA 20

lntronlO-335 19221

CFTR- IntronlO- + ACAGCUAAAAUGACAAUCAAA 21

3141 22023

CFTR- IntronlO- + CACAGCUAAAAUGACAAUCAAA 22

3142 22024

CFTR- IntronlO- + CCACAGCUAAAAUGACAAUCAAA 23

3143 22025

CFTR- IntronlO- + ACCACAGCUAAAAUGACAAUCAAA 24

3144 22026

805

5535.1 CFTR- IntronlO- + AGGAUAUCUUAGGUCAAA 18

3145 22027

CFTR- IntronlO- + UAGGAUAUCUUAGGUCAAA 19

3146 22028

CFTR- IntronlO- + UUAGGAUAUCUUAGGUCAAA 20

3147 22029

CFTR- IntronlO- + CUU AGGAUAUCUUAGGUCAAA 21

3148 22030

CFTR- IntronlO- + CCUUAGGAUAUCUUAGGUCAAA 22

3149 22031

CFTR- IntronlO- + CCCUUAGGAUAUCUUAGGUCAAA 23

3150 22032

CFTR- IntronlO- + UCCCUUAGGAUAUCUUAGGUCAAA 24

3151 22033

CFTR- IntronlO- + AAUGCAGGAGAAUGGAAA 18

3152 22034

CFTR- IntronlO- + GAAUGCAGGAGAAUGGAAA 19

3153 22035

CFTR- IntronlO- + GGAAUGCAGGAGAAUGGAAA 20

3154 22036

CFTR- IntronlO- + GGGAAUGCAGGAGAAUGGAAA 21

3155 22037

CFTR- IntronlO- + AGGGAAUGCAGGAGAAUGGAAA 22

3156 22038

CFTR- IntronlO- + GAGGGAAUGCAGGAGAAUGGAAA 23

3157 22039

CFTR- IntronlO- + UGAGGGAAUGCAGGAGAAUGGAAA 24

3158 22040

806

5535.1 CFTR- IntronlO- + C A A A U AC A U U C A A U G AAA 18

3159 22041

CFTR- IntronlO- + CCAAAUACAUUCAAUGAAA 19

3160 22042

CFTR- IntronlO- + CCCAAAUACAUUCAAUGAAA 20

3161 22043

CFTR- IntronlO- + GCCCAAAUACAUUCAAUGAAA 21

3162 22044

CFTR- IntronlO- + GGCCCAAAUACAUUCAAUGAAA 22

3163 22045

CFTR- IntronlO- + AGGCCCAAAUACAUUCAAUGAAA 23

3164 22046

CFTR- IntronlO- + CAGG CCCAAAU ACAU U CAAUG AAA 24

3165 22047

CFTR- IntronlO- + AGUGCAUAAAGGUUGAAA 18

3166 22048

CFTR- IntronlO- + GAGUGCAUAAAGGUUGAAA 19

3167 22049

CFTR- IntronlO- + AGAGUGCAU A A AG G U U G A A A 20

3168 22050

CFTR- IntronlO- + AAGAGUGCAUAAAGGUUGAAA 21

3169 22051

CFTR- IntronlO- + A A AG AG U G C A U A A AG G U U G AAA 22

3170 22052

CFTR- IntronlO- + CAAAGAGUGCAUAAAGGUUGAAA 23

3171 22053

CFTR- IntronlO- + GCAAAGAGUGCAUAAAGGUUGAAA 24

3172 22054

807

5535.1 CFTR- IntronlO- + UGCAUAUUGUUACAUAAA 18

3173 22055

CFTR- IntronlO- + CUGCAUAUUGUUACAUAAA 19

3174 22056

CFTR- IntronlO- + UCUGCAUAUUGUUACAUAAA 20

3175 22057

CFTR- IntronlO- + CUCUGCAUAUUGUUACAUAAA 21

3176 22058

CFTR- IntronlO- + ACUCUGCAUAUUGUUACAUAAA 22

3177 22059

CFTR- IntronlO- + AACUCUGCAUAUUGUUACAUAAA 23

3178 22060

CFTR- IntronlO- + AAACUCUGCAUAUUGUUACAUAAA 24

3179 22061

CFTR- IntronlO- + UCGUAUGUAGGAAAACAA 18

3180 22062

CFTR- IntronlO- + UUCGUAUGU AG G A A A A C A A 19

3181 22063

CFTR- IntronlO- + UUUCGUAUGUAGGAAAACAA 20

3182 22064

CFTR- IntronlO- + GUUUCGUAUGUAGGAAAACAA 21

3183 22065

CFTR- IntronlO- + UGUUUCGUAUGUAGGAAAACAA 22

3184 22066

CFTR- IntronlO- + CUGUUUCGUAUGUAGGAAAACAA 23

3185 22067

CFTR- IntronlO- + GCUGUUUCGUAUGUAGGAAAACAA 24

3186 22068

808

5535.1 CFTR- IntronlO- + AACCAAAUAAACAAACAA 18

3187 22069

CFTR- IntronlO- + AAACCAAAUAAACAAACAA 19

3188 22070

CFTR- IntronlO- + A A A AC C A A A U AAACAAACAA 20

1099 19984

CFTR- IntronlO- + AAAAACCAAAUAAACAAACAA 21

3189 22071

CFTR- IntronlO- + UAAAAACCAAAUAAACAAACAA 22

3190 22072

CFTR- IntronlO- + G UAAAAACCAAAUAAACAAACAA 23

3191 22073

CFTR- IntronlO- + AGUAAAAACCAAAUAAACAAACAA 24

3192 22074

CFTR- IntronlO- + UGUGUGGCUUAUAAACAA 18

3193 22075

CFTR- IntronlO- + CUGUGUGGCUUAUAAACAA 19

3194 22076

CFTR- IntronlO- + ACUGUGUGGCUUAUAAACAA 20

3195 22077

CFTR- IntronlO- + AACUGUGUGGCUUAUAAACAA 21

3196 22078

CFTR- IntronlO- + GAACUGUGUGGCUUAUAAACAA 22

3197 22079

CFTR- IntronlO- + UGAACUGUGUGGCUUAUAAACAA 23

3198 22080

CFTR- IntronlO- + AUGAACUGUGUGGCUUAUAAACAA 24

3199 22081

809

5535.1 CFTR- IntronlO- + CAGCUGUGAUGCAGACAA 18

3200 22082

CFTR- IntronlO- + UCAGCUGUGAUGCAGACAA 19

3201 22083

CFTR- IntronlO- + UUCAGCUGUGAUGCAGACAA 20

3202 22084

CFTR- IntronlO- + CUUCAGCUGUGAUGCAGACAA 21

3203 22085

CFTR- IntronlO- + GCUUCAGCUGUGAUGCAGACAA 22

3204 22086

CFTR- IntronlO- + UGCUUCAGCUGUGAUGCAGACAA 23

3205 22087

CFTR- IntronlO- + CUGCUUCAGCUGUGAUGCAGACAA 24

3206 22088

CFTR- IntronlO- + UAAUGAGUU ACAAU ACAA 18

3207 22089

CFTR- IntronlO- + U U AAUG AG U U ACAAU ACAA 19

3208 22090

CFTR- IntronlO- + AU U AAUG AG U U ACAAU ACAA 20

3209 22091

CFTR- IntronlO- + AAU U AAUG AG U U ACAAU ACAA 21

3210 22092

CFTR- IntronlO- + AAAU U AAUG AG U U ACAAU ACAA 22

3211 22093

CFTR- IntronlO- + U AAAU U AAUG AG U U ACAAU ACAA 23

3212 22094

CFTR- IntronlO- + AU AAAU U AAUG AG U U ACAAU ACAA 24

3213 22095

810

5535.1 CFTR- IntronlO- + AGCUUACCGUAAUAGCAA 18

3214 22096

CFTR- IntronlO- + GAGCUUACCGUAAUAGCAA 19

3215 22097

CFTR- IntronlO- + UGAGCUUACCGUAAUAGCAA 20

3216 22098

CFTR- IntronlO- + UUGAGCUUACCGUAAUAGCAA 21

3217 22099

CFTR- IntronlO- + CUUGAGCUUACCGUAAUAGCAA 22

3218 22100

CFTR- IntronlO- + GCUUGAGCUUACCGUAAUAGCAA 23

3219 22101

CFTR- IntronlO- + UGCUUGAGCUUACCGUAAUAGCAA 24

3220 22102

CFTR- IntronlO- + GGUCAAUUGUAUUAGCAA 18

3221 22103

CFTR- IntronlO- + GGGUCAAUUGUAUUAGCAA 19

3222 22104

CFTR- IntronlO- + AGGGUCAAUUGUAUUAGCAA 20

3223 22105

CFTR- IntronlO- + AAGGGUCAAUUGUAUUAGCAA 21

3224 22106

CFTR- IntronlO- + U AAGGG U CAAU UG U AU U AG CAA 22

3225 22107

CFTR- IntronlO- + U U AAGGG U CAAU UG U AU U AG CAA 23

3226 22108

CFTR- IntronlO- + U U U AAGGG U CAAU UG U AU U AG CAA 24

3227 22109

811

5535.1 CFTR- IntronlO- + UUAGU AAAAAAAAAU CAA 18

3228 22110

CFTR- IntronlO- + AU U AG U AAAAAAAAAU CAA 19

3229 22111

CFTR- IntronlO- + AAUUAGU AAAAAAAAAU CAA 20

3230 22112

CFTR- IntronlO- + AAAU U AG U AAAAAAAAAU CAA 21

3231 22113

CFTR- IntronlO- + AAAAUUAGU AAAAAAAAAU CAA 22

3232 22114

CFTR- IntronlO- + CAAAAU U AG U AAAAAAAAAU CAA 23

3233 22115

CFTR- IntronlO- + ACAAAAUUAGUAAAAAAAAAUCAA 24

3234 22116

CFTR- IntronlO- + AG C U A A A A U G AC A A U C A A 18

3235 22117

CFTR- IntronlO- + C AG C U A A A A U G AC A A U C A A 19

3236 22118

CFTR- IntronlO- + A C AG C U A A A A U G AC A A U C A A 20

3237 22119

CFTR- IntronlO- + CACAGCUAAAAUGACAAUCAA 21

3238 22120

CFTR- IntronlO- + C C AC AG C U A A A A U G AC A A U CAA 22

3239 22121

CFTR- IntronlO- + ACCACAGCUAAAAUGACAAUCAA 23

3240 22122

CFTR- IntronlO- + UACCACAGCUAAAAUGACAAUCAA 24

3241 22123

812

5535.1 CFTR- IntronlO- + CUGAAGCGG A A AG G U C A A 18

3242 22124

CFTR- IntronlO- + G C U G A AG CG G A A AG G U C A A 19

3243 22125

CFTR- IntronlO- + GGCUGAAGCGGAAAGGUCAA 20

3244 22126

CFTR- IntronlO- + AGGCUGAAGCGGAAAGGUCAA 21

3245 22127

CFTR- IntronlO- + G AG G C UGAAG CG G AAAG G U CAA 22

3246 22128

CFTR- IntronlO- + GGAGGCUGAAGCGGAAAGGUCAA 23

3247 22129

CFTR- IntronlO- + GGGAGGCUGAAGCGGAAAGGUCAA 24

3248 22130

CFTR- IntronlO- + CACCUGAAAUAUAUUCAA 18

3249 22131

CFTR- IntronlO- + UCACCUGAAAUAUAUUCAA 19

3250 22132

CFTR- IntronlO- + AUCACCUGAAAUAUAUUCAA 20

3251 22133

CFTR- IntronlO- + UAUCACCUGAAAUAUAUUCAA 21

3252 22134

CFTR- IntronlO- + AUAUCACCUGAAAUAUAUUCAA 22

3253 22135

CFTR- IntronlO- + AAUAUCACCUGAAAUAUAUUCAA 23

3254 22136

CFTR- IntronlO- + UAAUAUCACCUGAAAUAUAUUCAA 24

3255 22137

813

5535.1 CFTR- IntronlO- + AAAAAAAAAAAAAAAGAA 18

3256 22138

CFTR- IntronlO- + AAAAAAAAAAAAAAAAGAA 19

3257 22139

CFTR- IntronlO- + AAAAAAAAAAAAAAAAAGAA 20

3258 22140

CFTR- IntronlO- + AAAAAAAAAAAAAAAAAAGAA 21

3259 22141

CFTR- IntronlO- + AAAAAAAAAAAAAAAAAAAGAA 22

3260 22142

CFTR- IntronlO- + AAAAAAAAAAAAAAAAAAAAGAA 23

3261 22143

CFTR- IntronlO- + AAAAAAAAAAAAAAAAAAAAAGAA 24

3262 22144

CFTR- IntronlO- + GAAAUAUAUU CAAAAG AA 18

3263 22145

CFTR- IntronlO- + UGAAAUAUAUUCAAAAGAA 19

3264 22146

CFTR- IntronlO- + CUGAAAUAUAUUCAAAAGAA 20

1103 19988

CFTR- IntronlO- + CCUGAAAUAUAUUCAAAAGAA 21

3265 22147

CFTR- IntronlO- + ACCUGAAAUAUAUUCAAAAGAA 22

3266 22148

CFTR- IntronlO- + CACCUGAAAUAUAUUCAAAAGAA 23

3267 22149

CFTR- IntronlO- + U CACCUG AAAU AU AU U CAAAAG AA 24

3268 22150

814

5535.1 CFTR- IntronlO- + AAAAAUACGAUAUAAGAA 18

3269 22151

CFTR- IntronlO- + CAAAAAUACGAUAUAAGAA 19

3270 22152

CFTR- IntronlO- + GCAAAAAUACGAUAUAAGAA 20

3271 22153

CFTR- IntronlO- + UGCAAAAAUACGAUAUAAGAA 21

3272 22154

CFTR- IntronlO- + U UGCAAAAAU ACG AU AU AAG AA 22

3273 22155

CFTR- IntronlO- + GUUGCAAAAAUACGAUAUAAGAA 23

3274 22156

CFTR- IntronlO- + AGUUGCAAAAAUACGAUAUAAGAA 24

3275 22157

CFTR- IntronlO- + UGAGGGAAUGCAGGAGAA 18

3276 22158

CFTR- IntronlO- + AUGAGGGAAUGCAGGAGAA 19

3277 22159

CFTR-

+ GAUGAGGGAAUGCAGGAGAA 20

lntronlO-649 19535

CFTR- IntronlO- + GGAUGAGGGAAUGCAGGAGAA 21

3278 22160

CFTR- IntronlO- + UGGAUGAGGGAAUGCAGGAGAA 22

3279 22161

CFTR- IntronlO- + UUGGAUGAGGGAAUGCAGGAGAA 23

3280 22162

CFTR- IntronlO- + GUUGGAUGAGGGAAUGCAGGAGAA 24

3281 22163

CFTR-

+ AAUAAACAAACAAAGGAA 18

IntronlO- 22164

815

5535.1 3282

CFTR- IntronlO- + AAAUAAACAAACAAAGGAA 19

3283 22165

CFTR- IntronlO- + C A A A U A A AC A A AC A A AG G A A 20

3284 22166

CFTR- IntronlO- + CCAAAUAAACAAACAAAGGAA 21

3285 22167

CFTR- IntronlO- + ACCAAAUAAACAAACAAAGGAA 22

3286 22168

CFTR- IntronlO- + AACCAAAUAAACAAACAAAGGAA 23

3287 22169

CFTR- IntronlO- + AAACCAAAUAAACAAACAAAGGAA 24

3288 22170

CFTR- IntronlO- + A A A AC U GAGUAGAAGGAA 18

3289 22171

CFTR- IntronlO- + U A A A AC U GAGUAGAAGGAA 19

3290 22172

CFTR-

+ CUAAAACUGAGUAGAAGGAA 20

lntronlO-349 19235

CFTR- IntronlO- + ACUAAAACUGAGUAGAAGGAA 21

3291 22173

CFTR- IntronlO- + GACUAAAACUGAGUAGAAGGAA 22

3292 22174

CFTR- IntronlO- + UGACUAAAACUGAGUAGAAGGAA 23

3293 22175

CFTR- IntronlO- + CUGACUAAAACUGAGUAGAAGGAA 24

3294 22176

CFTR- IntronlO- + UAAACAGAAUCAGGGGAA 18

3295 22177

816

5535.1 CFTR- IntronlO- + U U A A AC AG A A U C AG G G G A A 19

3296 22178

CFTR- IntronlO- + U U U A A AC AG A A U C AG G G G A A 20

3297 22179

CFTR- IntronlO- + AUUUAAACAGAAUCAGGGGAA 21

3298 22180

CFTR- IntronlO- + UAUUUAAACAGAAUCAGGGGAA 22

3299 22181

CFTR- IntronlO- + CUAUUUAAACAGAAUCAGGGGAA 23

3300 22182

CFTR- IntronlO- + GCUAUUUAAACAGAAUCAGGGGAA 24

3301 22183

CFTR- IntronlO- + GCACUUUGGGAGGCUGAA 18

3302 22184

CFTR- IntronlO- + AGCACUUUGGGAGGCUGAA 19

3303 22185

CFTR- IntronlO- + CAGCACUUUGGGAGGCUGAA 20

3304 22186

CFTR- IntronlO- + CCAGCACUUUGGGAGGCUGAA 21

3305 22187

CFTR- IntronlO- + CCCAGCACUUUGGGAGGCUGAA 22

3306 22188

CFTR- IntronlO- + ACCCAGCACUUUGGGAGGCUGAA 23

3307 22189

CFTR- IntronlO- + AACCCAGCACUUUGGGAGGCUGAA 24

3308 22190

CFTR- IntronlO- + GUACAUUUAAUAUCUGAA 18

3309 22191

817

5535.1 CFTR- IntronlO- + UGUACAUUUAAUAUCUGAA 19

3310 22192

CFTR- IntronlO- + AUGUACAUUUAAUAUCUGAA 20

3311 22193

CFTR- IntronlO- + GAUGUACAUUUAAUAUCUGAA 21

3312 22194

CFTR- IntronlO- + UGAUGUACAUUUAAUAUCUGAA 22

3313 22195

CFTR- IntronlO- + AUGAUGUACAUUUAAUAUCUGAA 23

3314 22196

CFTR- IntronlO- + AAUGAUGUACAUUUAAUAUCUGAA 24

3315 22197

CFTR- IntronlO- + A A A A A A A U U C AC A A A U A A 18

3316 22198

CFTR- IntronlO- + AAAAAAAAUUCACAAAUAA 19

3317 22199

CFTR- IntronlO- + GAAAAAAAAUUCACAAAUAA 20

3318 22200

CFTR- IntronlO- + UGAAAAAAAAUUCACAAAUAA 21

3319 22201

CFTR- IntronlO- + CUGAAAAAAAAUUCACAAAUAA 22

3320 22202

CFTR- IntronlO- + ACUGAAAAAAAAUUCACAAAUAA 23

3321 22203

CFTR- IntronlO- + AACUGAAAAAAAAUUCACAAAUAA 24

3322 22204

CFTR- IntronlO- + UGAGGCAAUGAUCAAUAA 18

3323 22205

818

5535.1 CFTR- IntronlO- + GUGAGGCAAUGAUCAAUAA 19

3324 22206

CFTR- IntronlO- + AGUGAGGCAAUGAUCAAUAA 20

3325 22207

CFTR- IntronlO- + UAGUGAGGCAAUGAUCAAUAA 21

3326 22208

CFTR- IntronlO- + AUAGUGAGGCAAUGAUCAAUAA 22

3327 22209

CFTR- IntronlO- + CAUAGUGAGGCAAUGAUCAAUAA 23

3328 22210

CFTR- IntronlO- + CCAUAGUGAGGCAAUGAUCAAUAA 24

3329 22211

CFTR- IntronlO- + AGAACCUAUAAGGAAUAA 18

3330 22212

CFTR- IntronlO- + CAGAACCUAUAAGGAAUAA 19

3331 22213

CFTR- IntronlO- + ACAGAACCUAUAAGGAAUAA 20

3332 22214

CFTR- IntronlO- + UACAGAACCUAUAAGGAAUAA 21

3333 22215

CFTR- IntronlO- + U UACAGAACCUAUAAGGAAUAA 22

3334 22216

CFTR- IntronlO- + AUUACAGAACCUAUAAGGAAUAA 23

3335 22217

CFTR- IntronlO- + AAUUACAGAACCUAUAAGGAAUAA 24

3336 22218

CFTR- IntronlO- + ACAGUGACUUCAUAAUAA 18

3337 22219

819

5535.1 CFTR- IntronlO- + UACAGUGACUUCAUAAUAA 19

3338 22220

CFTR- IntronlO- + AUACAGUGACUUCAUAAUAA 20

1111 19996

CFTR- IntronlO- + AAUACAGUGACUUCAUAAUAA 21

3339 22221

CFTR- IntronlO- + CAAUACAGUGACUUCAUAAUAA 22

3340 22222

CFTR- IntronlO- + ACAAUACAGUGACUUCAUAAUAA 23

3341 22223

CFTR- IntronlO- + GACAAUACAGUGACUUCAUAAUAA 24

3342 22224

CFTR- IntronlO- + UUACACUACUUAUAAUAA 18

3343 22225

CFTR- IntronlO- + U U U ACACU ACU U AU AAU AA 19

3344 22226

CFTR- IntronlO- + UUUUACACUACUUAUAAUAA 20

3345 22227

CFTR- IntronlO- + AUUUUACACUACUUAUAAUAA 21

3346 22228

CFTR- IntronlO- + UAUUUUACACUACUUAUAAUAA 22

3347 22229

CFTR- IntronlO- + AUAUUUUACACUACUUAUAAUAA 23

3348 22230

CFTR- IntronlO- + GAUAUUUUACACUACUUAUAAUAA 24

3349 22231

CFTR- IntronlO- + CAAGUAGAAAAAAGAUAA 18

3350 22232

820

5535.1 CFTR- IntronlO- + G C A AG U AG A A A A A AG A U A A 19

3351 22233

CFTR- IntronlO- + AGCAAGUAGAAAAAAGAUAA 20

3352 22234

CFTR- IntronlO- + AAGCAAGUAG A A A A A AG A U A A 21

3353 22235

CFTR- IntronlO- + A A AG C A AG U AG A A A A A AG A U A A 22

3354 22236

CFTR- IntronlO- + CAAAGCAAGUAGAAAAAAGAUAA 23

3355 22237

CFTR- IntronlO- + GCAAAGCAAGUAGAAAAAAGAUAA 24

3356 22238

CFTR- IntronlO- + AUAAUAUACAAGAUAUAA 18

3357 22239

CFTR- IntronlO- + AAUAAUAUACAAGAUAUAA 19

3358 22240

CFTR- IntronlO- + UAAUAAUAUACAAGAUAUAA 20

3359 22241

CFTR- IntronlO- + GUAAUAAUAUACAAGAUAUAA 21

3360 22242

CFTR- IntronlO- + AG UAAUAAUAUACAAGAUAUAA 22

3361 22243

CFTR- IntronlO- + UAGUAAUAAUAUACAAGAUAUAA 23

3362 22244

CFTR- IntronlO- + CUAGUAAUAAUAUACAAGAUAUAA 24

3363 22245

CFTR- IntronlO- + UAACUUUAUGCUAACUAA 18

3364 22246

821

5535.1 CFTR- IntronlO- + CUAACUUUAUGCUAACUAA 19

3365 22247

CFTR- IntronlO- + CCUAACUUUAUGCUAACUAA 20

3366 22248

CFTR- IntronlO- + ACCUAACUUUAUGCUAACUAA 21

3367 22249

CFTR- IntronlO- + AACCUAACUUUAUGCUAACUAA 22

3368 22250

CFTR- IntronlO- + AAACCUAACUUUAUGCUAACUAA 23

3369 22251

CFTR- IntronlO- + CAAACCUAACUUUAUGCUAACUAA 24

3370 22252

CFTR- IntronlO- + AG U AAAG U AACAAAG UAA 18

3371 22253

CFTR- IntronlO- + CAG U AAAG U AACAAAG UAA 19

3372 22254

CFTR- IntronlO- + U CAG UAAAGU AACAAAG UAA 20

3373 22255

CFTR- IntronlO- + A U C AG U AAAG U AACAAAG U A A 21

3374 22256

CFTR- IntronlO- + U A U C AG U AAAG U AACAAAG U A A 22

3375 22257

CFTR- IntronlO- + U UAU CAG UAAAGU AACAAAG UAA 23

3376 22258

CFTR- IntronlO- + U U UAU CAG U AAAG U AACAAAG UAA 24

3377 22259

CFTR- IntronlO- + AG C U A A U AAA U AAAG U A A 18

3378 22260

822

5535.1 CFTR- IntronlO- + A AG C U A A U AAA U AAAG U A A 19

3379 22261

CFTR- IntronlO- + AAAG CU AAU AAAU AAAG UAA 20

3380 22262

CFTR- IntronlO- + UAAAGCU AAU AAAU AAAG UAA 21

3381 22263

CFTR- IntronlO- + U U AAAG CU AAU AAAU AAAG UAA 22

3382 22264

CFTR- IntronlO- + U U U AAAG CU AAU AAAU AAAG UAA 23

3383 22265

CFTR- IntronlO- + AUUUAAAGCUAAUAAAUAAAGUAA 24

3384 22266

CFTR- IntronlO- + UUCUAGAAAACAAUGUAA 18

3385 22267

CFTR- IntronlO- + U U U CU AG AAAACAAUG UAA 19

3386 22268

CFTR- IntronlO- + U U U U CU AG AAAACAAUG UAA 20

1114 19999

CFTR- IntronlO- + AUUUUCUAGAAAACAAUGUAA 21

3387 22269

CFTR- IntronlO- + GAUUUUCUAGAAAACAAUGUAA 22

3388 22270

CFTR- IntronlO- + AG AU U U U CU AG AAAACAAUG UAA 23

3389 22271

CFTR- IntronlO- + CAG AU U U U CU AG AAAACAAUG UAA 24

3390 22272

CFTR- IntronlO- + UAUAAGUGUGGAGUGUAA 18

3391 22273

823

5535.1 CFTR- IntronlO- + GUAUAAGUGUGGAGUGUAA 19

3392 22274

CFTR-

+ GGUAUAAGUGUGGAGUGUAA 20

lntronlO-72 18958

CFTR- IntronlO- + GGGUAUAAGUGUGGAGUGUAA 21

3393 22275

CFTR- IntronlO- + GGGGUAUAAGUGUGGAGUGUAA 22

3394 22276

CFTR- IntronlO- + UGGGGUAUAAGUGUGGAGUGUAA 23

3395 22277

CFTR- IntronlO- + AUGGGGUAUAAGUGUGGAGUGUAA 24

3396 22278

CFTR- IntronlO- + UGAACUCUAAUCUAUUAA 18

3397 22279

CFTR- IntronlO- + UUGAACUCUAAUCUAUUAA 19

3398 22280

CFTR- IntronlO- + AUUGAACUCUAAUCUAUUAA 20

3399 22281

CFTR- IntronlO- + AAUUGAACUCUAAUCUAUUAA 21

3400 22282

CFTR- IntronlO- + GAAUUGAACUCUAAUCUAUUAA 22

3401 22283

CFTR- IntronlO- + UGAAUUGAACUCUAAUCUAUUAA 23

3402 22284

CFTR- IntronlO- + CUGAAUUGAACUCUAAUCUAUUAA 24

3403 22285

CFTR- IntronlO- + GCUUAACCCAUCUAUUAA 18

3404 22286

CFTR-

+ GGCUUAACCCAUCUAUUAA 19

IntronlO- 22287

824

5535.1 3405

CFTR- IntronlO- + UGGCUUAACCCAUCUAUUAA 20

3406 22288

CFTR- IntronlO- + UUGGCUUAACCCAUCUAUUAA 21

3407 22289

CFTR- IntronlO- + GUUGGCUUAACCCAUCUAUUAA 22

3408 22290

CFTR- IntronlO- + AGUUGGCUUAACCCAUCUAUUAA 23

3409 22291

CFTR- IntronlO- + CAGUUGGCUUAACCCAUCUAUUAA 24

3410 22292

CFTR- IntronlO- + AAUUUUCCAAUGUAUUAA 18

3411 22293

CFTR- IntronlO- + AAAU UUUCCAAUGUAUUAA 19

3412 22294

CFTR- IntronlO- + AAAAUUUUCCAAUGUAUUAA 20

3413 22295

CFTR- IntronlO- + AAAAAU UUUCCAAUGUAUUAA 21

3414 22296

CFTR- IntronlO- + CAAAAAU UUUCCAAUGUAUUAA 22

3415 22297

CFTR- IntronlO- + CCAAAAAU U U U CCAAUG U AU U AA 23

3416 22298

CFTR- IntronlO- + CCCAAAAAUUUUCCAAUGUAUUAA 24

3417 22299

CFTR- IntronlO- + AGCCUAGAUGAUUAUUAA 18

3418 22300

CFTR-

+ CAGCCUAGAUGAUUAUUAA 19

IntronlO- 22301

825

5535.1 3419

CFTR- IntronlO- + GCAGCCUAGAUGAUUAUUAA 20

3420 22302

CFTR- IntronlO- + UGCAGCCUAGAUGAUUAUUAA 21

3421 22303

CFTR- IntronlO- + UUGCAGCCUAGAUGAUUAUUAA 22

3422 22304

CFTR- IntronlO- + UUUGCAGCCUAGAUGAUUAUUAA 23

3423 22305

CFTR- IntronlO- + UUUUGCAGCCUAGAUGAUUAUUAA 24

3424 22306

CFTR- IntronlO- + UAUUUCCUCAAUAGUUAA 18

3425 22307

CFTR- IntronlO- + UUAUUUCCUCAAUAGUUAA 19

3426 22308

CFTR- IntronlO- + UUUAUUUCCUCAAUAGUUAA 20

3427 22309

CFTR- IntronlO- + AUUUAUUUCCUCAAUAGUUAA 21

3428 22310

CFTR- IntronlO- + AAUUUAUUUCCUCAAUAGUUAA 22

3429 22311

CFTR- IntronlO- + AAAU UUAUUUCCUCAAUAGUUAA 23

3430 22312

CFTR- IntronlO- + U AAAU UUAUUUCCUCAAUAGUUAA 24

3431 22313

CFTR- IntronlO- + CAACAUUCUUGGAAAACA 18

3432 22314

CFTR-

+ ACAACAUUCUUGGAAAACA 19

IntronlO- 22315

826

5535.1 3433

CFTR- IntronlO- + AACAACAUUCUUGGAAAACA 20

3434 22316

CFTR- IntronlO- + GAACAACAUUCUUGGAAAACA 21

3435 22317

CFTR- IntronlO- + UGAACAACAUUCUUGGAAAACA 22

3436 22318

CFTR- IntronlO- + UUGAACAACAUUCUUGGAAAACA 23

3437 22319

CFTR- IntronlO- + U U UG AACAACAU U CU U GG AAAACA 24

3438 22320

CFTR- IntronlO- + AAUGAAACAAAUAAAACA 18

3439 22321

CFTR- IntronlO- + AAAUGAAACAAAUAAAACA 19

3440 22322

CFTR- IntronlO- + GAAAUGAAACAAAUAAAACA 20

3441 22323

CFTR- IntronlO- + AGAAAUGAAACAAAUAAAACA 21

3442 22324

CFTR- IntronlO- + AAGAAAUGAAACAAAUAAAACA 22

3443 22325

CFTR- IntronlO- + AAAGAAAUGAAACAAAUAAAACA 23

3444 22326

CFTR- IntronlO- + AAAAGAAAUGAAACAAAUAAAACA 24

3445 22327

CFTR- IntronlO- + AAACCAAAUAAACAAACA 18

3446 22328

CFTR-

+ AAAACCAAAUAAACAAACA 19

IntronlO- 22329

827

5535.1 3447

CFTR- IntronlO- + AAAAACCAAAUAAACAAACA 20

3448 22330

CFTR- IntronlO- + UAAAAACCAAAUAAACAAACA 21

3449 22331

CFTR- IntronlO- + GUAAAAACCAAAUAAACAAACA 22

3450 22332

CFTR- IntronlO- + AG UAAAAACCAAAUAAACAAACA 23

3451 22333

CFTR- IntronlO- + AAGUAAAAACCAAAUAAACAAACA 24

3452 22334

CFTR- IntronlO- + AAACUGUAAAUACAAACA 18

3453 22335

CFTR- IntronlO- + AAAACUGUAAAUACAAACA 19

3454 22336

CFTR- IntronlO- + UAAAACUGUAAAUACAAACA 20

3455 22337

CFTR- IntronlO- + UUAAAACUGUAAAUACAAACA 21

3456 22338

CFTR- IntronlO- + CUUAAAACUGUAAAUACAAACA 22

3457 22339

CFTR- IntronlO- + ACUUAAAACUGUAAAUACAAACA 23

3458 22340

CFTR- IntronlO- + AACUUAAAACUGUAAAUACAAACA 24

3459 22341

CFTR- IntronlO- + GACAAUCAAAUGGGAACA 18

3460 22342

CFTR-

+ UGACAAUCAAAUGGGAACA 19

IntronlO- 22343

828

5535.1 3461

CFTR-

+ AUGACAAUCAAAUGGGAACA 20

lntronlO-363 19249

CFTR- IntronlO- + AAUGACAAUCAAAUGGGAACA 21

3462 22344

CFTR- IntronlO- + AAAUGACAAUCAAAUGGGAACA 22

3463 22345

CFTR- IntronlO- + AAAAUGACAAUCAAAUGGGAACA 23

3464 22346

CFTR- IntronlO- + UAAAAUGACAAUCAAAUGGGAACA 24

3465 22347

CFTR- IntronlO- + AACCUAUAAGGAAUAACA 18

3466 22348

CFTR- IntronlO- + GAACCUAUAAGGAAUAACA 19

3467 22349

CFTR-

+ AGAACCUAUAAGGAAUAACA 20

lntronlO-364 19250

CFTR- IntronlO- + CAGAACCUAUAAGGAAUAACA 21

3468 22350

CFTR- IntronlO- + ACAGAACCUAUAAGGAAUAACA 22

3469 22351

CFTR- IntronlO- + UACAGAACCUAUAAGGAAUAACA 23

3470 22352

CFTR- IntronlO- + UUACAGAACCUAUAAGGAAUAACA 24

3471 22353

CFTR- IntronlO- + GAGAGAGAACUGCUCACA 18

3472 22354

CFTR- IntronlO- + GGAGAGAGAACUGCUCACA 19

3473 22355

829

5535.1 CFTR- IntronlO- + UGGAGAGAGAACUGCUCACA 20

1122 20007

CFTR- IntronlO- + CUGGAGAGAGAACUGCUCACA 21

3474 22356

CFTR- IntronlO- + ACUGGAGAGAGAACUGCUCACA 22

3475 22357

CFTR- IntronlO- + UACUGGAGAGAGAACUGCUCACA 23

3476 22358

CFTR- IntronlO- + UUACUGGAGAGAGAACUGCUCACA 24

3477 22359

CFTR- IntronlO- + UUUACAAUUCUUAUUACA 18

3478 22360

CFTR- IntronlO- + UUUUACAAUUCUUAUUACA 19

3479 22361

CFTR- IntronlO- + AUUUUACAAUUCUUAUUACA 20

1125 20010

CFTR- IntronlO- + AAUUUUACAAUUCUUAUUACA 21

3480 22362

CFTR- IntronlO- + AAAU U U U ACAAU U CU U AU U ACA 22

3481 22363

CFTR- IntronlO- + UAAAUUUUACAAUUCUUAUUACA 23

3482 22364

CFTR- IntronlO- + G U AAAU U U U ACAAU U CU U AU U ACA 24

3483 22365

CFTR- IntronlO- + CAGGAGUUCAAGGUUACA 18

3484 22366

CFTR- IntronlO- + CCAGGAGUUCAAGGUUACA 19

3485 22367

830

5535.1 CFTR- IntronlO- + CCCAG GAG U U CAAG G U U ACA 20

3486 22368

CFTR- IntronlO- + GCCCAGG AG U U CAAGG U U ACA 21

3487 22369

CFTR- IntronlO- + AGCCCAGGAGUUCAAGGUUACA 22

3488 22370

CFTR- IntronlO- + GAGCCCAGGAGUUCAAGGUUACA 23

3489 22371

CFTR- IntronlO- + U GAG CCCAG GAG U U CAAG G U U AC A 24

3490 22372

CFTR- IntronlO- + UGAGCUAUGAUCACACCA 18

3491 22373

CFTR- IntronlO- + GUGAGCUAUGAUCACACCA 19

3492 22374

CFTR- IntronlO- + AGUGAGCUAUGAUCACACCA 20

3493 22375

CFTR- IntronlO- + CAGUGAGCUAUGAUCACACCA 21

3494 22376

CFTR- IntronlO- + ACAGUGAGCUAUGAUCACACCA 22

3495 22377

CFTR- IntronlO- + UACAGUGAGCUAUGAUCACACCA 23

3496 22378

CFTR- IntronlO- + UUACAGUGAGCUAUGAUCACACCA 24

3497 22379

CFTR- IntronlO- + GGCCUCUAAUCUCACCCA 18

3498 22380

CFTR- IntronlO- + UGGCCUCUAAUCUCACCCA 19

3499 22381

831

5535.1 CFTR- IntronlO- + GUGGCCUCUAAUCUCACCCA 20

3500 22382

CFTR- IntronlO- + AGUGGCCUCUAAUCUCACCCA 21

3501 22383

CFTR- IntronlO- + CAGUGGCCUCUAAUCUCACCCA 22

3502 22384

CFTR- IntronlO- + CCAGUGGCCUCUAAUCUCACCCA 23

3503 22385

CFTR- IntronlO- + UCCAGUGGCCUCUAAUCUCACCCA 24

3504 22386

CFTR- IntronlO- + CAGCUAAAGUAUUACCCA 18

3505 22387

CFTR- IntronlO- + ACAGCUAAAG U AU U ACCCA 19

3506 22388

CFTR- IntronlO- + UACAGCUAAAGUAUUACCCA 20

3507 22389

CFTR- IntronlO- + AU ACAG CU AAAG U AU U ACCCA 21

3508 22390

CFTR- IntronlO- + UAUACAGCUAAAGUAUUACCCA 22

3509 22391

CFTR- IntronlO- + AUAUACAGCUAAAGUAUUACCCA 23

3510 22392

CFTR- IntronlO- + AAUAUACAGCUAAAGUAUUACCCA 24

3511 22393

CFTR- IntronlO- + AGUGUUUAAAUAUUCCCA 18

3512 22394

CFTR- IntronlO- + AAGUGUUUAAAUAUUCCCA 19

3513 22395

CFTR- + G AAG UG U U U AAAU AU U CCCA 20 18962

832

5535.1 lntronlO-76

CFTR- IntronlO- + AGAAGUGUUUAAAUAUUCCCA 21

3514 22396

CFTR- IntronlO- + CAGAAGUGUUUAAAUAUUCCCA 22

3515 22397

CFTR- IntronlO- + U CAG AAG UG U U U AAAU AU U CCCA 23

3516 22398

CFTR- IntronlO- + CUCAGAAGUGUUUAAAUAUUCCCA 24

3517 22399

CFTR- IntronlO- + UAGUAUUAAGUAUAGCCA 18

3518 22400

CFTR- IntronlO- + UUAGUAUUAAGUAUAGCCA 19

3519 22401

CFTR- IntronlO- + AUUAGUAUUAAGUAUAGCCA 20

3520 22402

CFTR- IntronlO- + UAUUAGUAUUAAGUAUAGCCA 21

3521 22403

CFTR- IntronlO- + UUAUUAGUAUUAAGUAUAGCCA 22

3522 22404

CFTR- IntronlO- + GUUAUUAGUAUUAAGUAUAGCCA 23

3523 22405

CFTR- IntronlO- + AGUUAUUAGUAUUAAGUAUAGCCA 24

3524 22406

CFTR- IntronlO- + UGAGUAUACUUUAUGCCA 18

3525 22407

CFTR- IntronlO- + GUGAGUAUACUUUAUGCCA 19

3526 22408

CFTR- IntronlO- + UGUGAGUAUACUUUAUGCCA 20

3527 22409

833

5535.1 CFTR- IntronlO- + AUGUGAGUAUACUUUAUGCCA 21

3528 22410

CFTR- IntronlO- + UAUGUGAGUAUACUUUAUGCCA 22

3529 22411

CFTR- IntronlO- + CUAUGUGAGUAUACUUUAUGCCA 23

3530 22412

CFTR- IntronlO- + ACUAUGUGAGUAUACUUUAUGCCA 24

3531 22413

CFTR- IntronlO- + GAAGGAAAGGAGGUAGCA 18

3532 22414

CFTR- IntronlO- + AG AAG G AAAG GAG G U AG CA 19

3533 22415

CFTR- IntronlO- + U AG AAG G AAAG GAG G U AG CA 20

3534 22416

CFTR- IntronlO- + G U AG AAG G AAAG GAG G U AG CA 21

3535 22417

CFTR- IntronlO- + AGUAGAAGGAAAGGAGGUAGCA 22

3536 22418

CFTR- IntronlO- + GAGUAGAAGGAAAGGAGGUAGCA 23

3537 22419

CFTR- IntronlO- + U G AG U AG AAG G AAAG GAG G U AG CA 24

3538 22420

CFTR- IntronlO- + UUCAACAUAUGAAUGGCA 18

3539 22421

CFTR- IntronlO- + UUUCAACAUAUGAAUGGCA 19

3540 22422

CFTR- IntronlO- + AUUUCAACAUAUGAAUGGCA 20

1128 20013

834

5535.1 CFTR- IntronlO- + GAUUUCAACAUAUGAAUGGCA 21

3541 22423

CFTR- IntronlO- + GGAUUUCAACAUAUGAAUGGCA 22

3542 22424

CFTR- IntronlO- + AGGAUUUCAACAUAUGAAUGGCA 23

3543 22425

CFTR- IntronlO- + UAGGAUUUCAACAUAUGAAUGGCA 24

3544 22426

CFTR- IntronlO- + CGGGAGGCGGAGCUUGCA 18

3545 22427

CFTR- IntronlO- + CCGGGAGGCGGAGCUUGCA 19

3546 22428

CFTR- IntronlO- + CCCGGGAGGCGGAGCUUGCA 20

3547 22429

CFTR- IntronlO- + ACCCGGGAGGCGGAGCUUGCA 21

3548 22430

CFTR- IntronlO- + AACCCGGGAGGCGGAGCUUGCA 22

3549 22431

CFTR- IntronlO- + GAACCCGGGAGGCGGAGCUUGCA 23

3550 22432

CFTR- IntronlO- + UGAACCCGGGAGGCGGAGCUUGCA 24

3551 22433

CFTR- IntronlO- + CGGGAGGCAGAGGUUGCA 18

3552 22434

CFTR- IntronlO- + CCGGGAGGCAGAGGUUGCA 19

3553 22435

CFTR- IntronlO- + CCCGGGAGGCAGAGGUUGCA 20

3554 22436

835

5535.1 CFTR- IntronlO- + GCCCGGGAGGCAGAGGUUGCA 21

3555 22437

CFTR- IntronlO- + AGCCCGGGAGGCAGAGGUUGCA 22

3556 22438

CFTR- IntronlO- + GAGCCCGGGAGGCAGAGGUUGCA 23

3557 22439

CFTR- IntronlO- + UGAGCCCGGGAGGCAGAGGUUGCA 24

3558 22440

CFTR- IntronlO- + GCUAUUUAAACAGAAUCA 18

3559 22441

CFTR- IntronlO- + UG CU AU U U AAACAG AAU CA 19

3560 22442

CFTR-

+ GUGCUAUUUAAACAGAAUCA 20

lntronlO-77 18963

CFTR- IntronlO- + AGUGCUAUUUAAACAGAAUCA 21

3561 22443

CFTR- IntronlO- + CAGUGCUAUUUAAACAGAAUCA 22

3562 22444

CFTR- IntronlO- + CCAGUGCUAUUUAAACAGAAUCA 23

3563 22445

CFTR- IntronlO- + UCCAGUGCUAUUUAAACAGAAUCA 24

3564 22446

CFTR- IntronlO- + AGUACAAAAGGACUAUCA 18

3565 22447

CFTR- IntronlO- + UAGUACAAAAGGACUAUCA 19

3566 22448

CFTR- IntronlO- + AUAGUACAAAAGGACUAUCA 20

3567 22449

CFTR-

+ GAUAGUACAAAAGGACUAUCA 21

IntronlO- 22450

836

5535.1 3568

CFTR- IntronlO- + UGAUAGUACAAAAGGACUAUCA 22

3569 22451

CFTR- IntronlO- + AUGAUAGUACAAAAGGACUAUCA 23

3570 22452

CFTR- IntronlO- + GAUGAUAGUACAAAAGGACUAUCA 24

3571 22453

CFTR- IntronlO- + UUAGGAUAUCUUAGGUCA 18

3572 22454

CFTR- IntronlO- + CUUAGGAUAUCUUAGGUCA 19

3573 22455

CFTR- IntronlO- + CCUUAGGAUAUCUUAGGUCA 20

3574 22456

CFTR- IntronlO- + CCCUUAGGAUAUCUUAGGUCA 21

3575 22457

CFTR- IntronlO- + UCCCUUAGGAUAUCUUAGGUCA 22

3576 22458

CFTR- IntronlO- + UUCCCUUAGGAUAUCUUAGGUCA 23

3577 22459

CFTR- IntronlO- + UUUCCCUUAGGAUAUCUUAGGUCA 24

3578 22460

CFTR- IntronlO- + UAUUCUUUUAUGUGGUCA 18

3579 22461

CFTR- IntronlO- + AUAUUCUUUUAUGUGGUCA 19

3580 22462

CFTR- IntronlO- + UAUAUUCUUUUAUGUGGUCA 20

3581 22463

CFTR-

+ AUAUAUUCUUUUAUGUGGUCA 21

IntronlO- 22464

837

5535.1 3582

CFTR- IntronlO- + AAUAUAUUCUUUUAUGUGGUCA 22

3583 22465

CFTR- IntronlO- + GAAUAUAUUCUUUUAUGUGGUCA 23

3584 22466

CFTR- IntronlO- + CGAAUAUAUUCUUUUAUGUGGUCA 24

3585 22467

CFTR- IntronlO- + CU U CACU AAAAU AAU U CA 18

3586 22468

CFTR- IntronlO- + GCUUCACUAAAAUAAUUCA 19

3587 22469

CFTR- IntronlO- + UGCUUCACUAAAAUAAUUCA 20

1133 20018

CFTR- IntronlO- + UUGCUUCACUAAAAUAAUUCA 21

3588 22470

CFTR- IntronlO- + AUUGCUUCACUAAAAUAAUUCA 22

3589 22471

CFTR- IntronlO- + UAUUGCUUCACUAAAAUAAUUCA 23

3590 22472

CFTR- IntronlO- + AUAUUGCUUCACUAAAAUAAUUCA 24

3591 22473

CFTR- IntronlO- + AAUCUAAAAGCUAAUUCA 18

3592 22474

CFTR- IntronlO- + AAAUCUAAAAGCUAAUUCA 19

3593 22475

CFTR-

+ UAAAUCUAAAAGCUAAUUCA 20

lntronlO-369 19255

CFTR- IntronlO- + GU AAAUCUAAAAGCUAAUUCA 21

3594 22476

838

5535.1 CFTR- IntronlO- + AGUAAAUCUAAAAGCUAAUUCA 22

3595 22477

CFTR- IntronlO- + AAGUAAAUCUAAAAGCUAAUUCA 23

3596 22478

CFTR- IntronlO- + UAAGUAAAUCUAAAAGCUAAUUCA 24

3597 22479

CFTR- IntronlO- + CAGG CCCAAAU ACAU U CA 18

3598 22480

CFTR- IntronlO- + GCAGGCCCAAAUACAUUCA 19

3599 22481

CFTR- IntronlO- + UGCAGGCCCAAAUACAUUCA 20

3600 22482

CFTR- IntronlO- + AUGCAGGCCCAAAUACAUUCA 21

3601 22483

CFTR- IntronlO- + UAUGCAGGCCCAAAUACAUUCA 22

3602 22484

CFTR- IntronlO- + AUAUGCAGGCCCAAAUACAUUCA 23

3603 22485

CFTR- IntronlO- + CAUAUGCAGGCCCAAAUACAUUCA 24

3604 22486

CFTR- IntronlO- + GAAUUGG UACAAAU U U CA 18

3605 22487

CFTR- IntronlO- + CGAAUUGGUACAAAUUUCA 19

3606 22488

CFTR-

+ ACGAAUUGGUACAAAUUUCA 20

lntronlO-370 19256

CFTR- IntronlO- + UACGAAUUGGUACAAAUUUCA 21

3607 22489

CFTR-

+ GU ACGAAUUGGUACAAAUUUCA 22

IntronlO- 22490

839

5535.1 3608

CFTR- IntronlO- + AGUACGAAUUGGUACAAAUUUCA 23

3609 22491

CFTR- IntronlO- + GAGUACGAAUUGGUACAAAUUUCA 24

3610 22492

CFTR- IntronlO- + UGAAAUAUAUUCAAAAGA 18

3611 22493

CFTR- IntronlO- + CUGAAAUAUAUUCAAAAGA 19

3612 22494

CFTR- IntronlO- + CCUGAAAUAUAUUCAAAAGA 20

3613 22495

CFTR- IntronlO- + ACCUGAAAUAUAUUCAAAAGA 21

3614 22496

CFTR- IntronlO- + CACCUGAAAUAUAUUCAAAAGA 22

3615 22497

CFTR- IntronlO- + UCACCUGAAAUAUAUUCAAAAGA 23

3616 22498

CFTR- IntronlO- + AUCACCUGAAAUAUAUUCAAAAGA 24

3617 22499

CFTR- IntronlO- + GAUGAGAGACAGUAAAGA 18

3618 22500

CFTR- IntronlO- + AGAUGAGAGACAGUAAAGA 19

3619 22501

CFTR- IntronlO- + CAGAUGAGAGACAGUAAAGA 20

3620 22502

CFTR- IntronlO- + ACAGAUGAGAGACAGUAAAGA 21

3621 22503

CFTR-

+ GACAGAUGAGAGACAGUAAAGA 22

IntronlO- 22504

840

5535.1 3622

CFTR- IntronlO- + GGACAGAUGAGAGACAGUAAAGA 23

3623 22505

CFTR- IntronlO- + UGGACAGAUGAGAGACAGUAAAGA 24

3624 22506

CFTR- IntronlO- + AAU AAU AACAU U U U AAG A 18

3625 22507

CFTR- IntronlO- + AAAU AAU AACAU U U U AAG A 19

3626 22508

CFTR- IntronlO- + AAAAU AAU AACAU U U U AAG A 20

3627 22509

CFTR- IntronlO- + AAAAAU AAU AACAU U U U AAG A 21

3628 22510

CFTR- IntronlO- + G AAAAAU AAU AACAU U U U AAG A 22

3629 22511

CFTR- IntronlO- + AG AAAAAU AAU AACAU U U U AAG A 23

3630 22512

CFTR- IntronlO- + AAG AAAAAU AAU AACAU U U U AAG A 24

3631 22513

CFTR- IntronlO- + UCCAGCCUGGGCGACAGA 18

3632 22514

CFTR- IntronlO- + CUCCAGCCUGGGCGACAGA 19

3633 22515

CFTR- IntronlO- + ACUCCAGCCUGGGCGACAGA 20

3634 22516

CFTR- IntronlO- + CACUCCAGCCUGGGCGACAGA 21

3635 22517

CFTR-

+ GCACUCCAGCCUGGGCGACAGA 22

IntronlO- 22518

841

5535.1 3636

CFTR- IntronlO- + UGCACUCCAGCCUGGGCGACAGA 23

3637 22519

CFTR- IntronlO- + CUGCACUCCAGCCUGGGCGACAGA 24

3638 22520

CFTR- IntronlO- + GUGUUCUCACAUGGCAGA 18

3639 22521

CFTR- IntronlO- + UGUGUUCUCACAUGGCAGA 19

3640 22522

CFTR- IntronlO- + CUGUGUUCUCACAUGGCAGA 20

3641 22523

CFTR- IntronlO- + GCUGUGUUCUCACAUGGCAGA 21

3642 22524

CFTR- IntronlO- + UGCUGUGUUCUCACAUGGCAGA 22

3643 22525

CFTR- IntronlO- + CUGCUGUGUUCUCACAUGGCAGA 23

3644 22526

CFTR- IntronlO- + CCUGCUGUGUUCUCACAUGGCAGA 24

3645 22527

CFTR- IntronlO- + UGAAUGGCAGGGGAGAGA 18

3646 22528

CFTR- IntronlO- + AUGAAUGGCAGGGGAGAGA 19

3647 22529

CFTR- IntronlO- + UAUGAAUGGCAGGGGAGAGA 20

3648 22530

CFTR- IntronlO- + AUAUGAAUGGCAGGGGAGAGA 21

3649 22531

CFTR-

+ CAUAUGAAUGGCAGGGGAGAGA 22

IntronlO- 22532

842

5535.1 3650

CFTR- IntronlO- + ACAUAUGAAUGGCAGGGGAGAGA 23

3651 22533

CFTR- IntronlO- + AACAUAUGAAUGGCAGGGGAGAGA 24

3652 22534

CFTR- IntronlO- + AUGAGGGAAUGCAGGAGA 18

3653 22535

CFTR- IntronlO- + GAUGAGGGAAUGCAGGAGA 19

3654 22536

CFTR- IntronlO- + GGAUGAGGGAAUGCAGGAGA 20

3655 22537

CFTR- IntronlO- + UGGAUGAGGGAAUGCAGGAGA 21

3656 22538

CFTR- IntronlO- + UUGGAUGAGGGAAUGCAGGAGA 22

3657 22539

CFTR- IntronlO- + GUUGGAUGAGGGAAUGCAGGAGA 23

3658 22540

CFTR- IntronlO- + GGUUGGAUGAGGGAAUGCAGGAGA 24

3659 22541

CFTR- IntronlO- + GAUCACGAGGUCAGGAGA 18

3660 22542

CFTR- IntronlO- + GGAUCACGAGGUCAGGAGA 19

3661 22543

CFTR- IntronlO- + CGGAUCACGAGGUCAGGAGA 20

3662 22544

CFTR- IntronlO- + GCGGAUCACGAGGUCAGGAGA 21

3663 22545

CFTR-

+ GGCGGAUCACGAGGUCAGGAGA 22

IntronlO- 22546

843

5535.1 3664

CFTR- IntronlO- + GGGCGGAUCACGAGGUCAGGAGA 23

3665 22547

CFTR- IntronlO- + CGGGCGGAUCACGAGGUCAGGAGA 24

3666 22548

CFTR- IntronlO- + UAGGAAAACAACUGGAGA 18

3667 22549

CFTR- IntronlO- + GUAGGAAAACAACUGGAGA 19

3668 22550

CFTR- IntronlO- + UGUAGGAAAACAACUGGAGA 20

3669 22551

CFTR- IntronlO- + AUGUAGGAAAACAACUGGAGA 21

3670 22552

CFTR- IntronlO- + UAUGUAGGAAAACAACUGGAGA 22

3671 22553

CFTR- IntronlO- + GUAUGUAGGAAAACAACUGGAGA 23

3672 22554

CFTR- IntronlO- + CGUAUGUAGGAAAACAACUGGAGA 24

3673 22555

CFTR- IntronlO- + UAUGCAAUUUACUGGAGA 18

3674 22556

CFTR- IntronlO- + AUAUGCAAUUUACUGGAGA 19

3675 22557

CFTR- IntronlO- + AAUAUGCAAUUUACUGGAGA 20

3676 22558

CFTR- IntronlO- + CAAUAUGCAAUUUACUGGAGA 21

3677 22559

CFTR-

+ GCAAUAUGCAAUUUACUGGAGA 22

IntronlO- 22560

844

5535.1 3678

CFTR- IntronlO- + UGCAAUAUGCAAUUUACUGGAGA 23

3679 22561

CFTR- IntronlO- + CUGCAAUAUGCAAUUUACUGGAGA 24

3680 22562

CFTR- IntronlO- + GAACUAGAGUCACAUAGA 18

3681 22563

CFTR- IntronlO- + UGAACUAGAGUCACAUAGA 19

3682 22564

CFTR- IntronlO- + GUGAACUAGAGUCACAUAGA 20

3683 22565

CFTR- IntronlO- + AGUGAACUAGAGUCACAUAGA 21

3684 22566

CFTR- IntronlO- + UAGUGAACUAGAGUCACAUAGA 22

3685 22567

CFTR- IntronlO- + U U AG UG AACU AG AG U CACAU AG A 23

3686 22568

CFTR- IntronlO- + AUUAGUGAACUAGAGUCACAUAGA 24

3687 22569

CFTR- IntronlO- + AUUGAUUAUAUAUAUAGA 18

3688 22570

CFTR- IntronlO- + UAUUGAUUAUAUAUAUAGA 19

3689 22571

CFTR- IntronlO- + AUAUUGAUUAUAUAUAUAGA 20

3690 22572

CFTR- IntronlO- + UAUAUUGAUUAUAUAUAUAGA 21

3691 22573

CFTR-

+ GUAUAUUGAUUAUAUAUAUAGA 22

IntronlO- 22574

845

5535.1 3692

CFTR- IntronlO- + UGUAUAUUGAUUAUAUAUAUAGA 23

3693 22575

CFTR- IntronlO- + AUGUAUAUUGAUUAUAUAUAUAGA 24

3694 22576

CFTR- IntronlO- + AGGAUCACUUUAUAUAGA 18

3695 22577

CFTR- IntronlO- + UAGGAUCACUUUAUAUAGA 19

3696 22578

CFTR- IntronlO- + CUAGGAUCACUUUAUAUAGA 20

3697 22579

CFTR- IntronlO- + UCUAGGAUCACUUUAUAUAGA 21

3698 22580

CFTR- IntronlO- + UUCUAGGAUCACUUUAUAUAGA 22

3699 22581

CFTR- IntronlO- + AUUCUAGGAUCACUUUAUAUAGA 23

3700 22582

CFTR- IntronlO- + GAUUCUAGGAUCACUUUAUAUAGA 24

3701 22583

CFTR- IntronlO- + UGACUAAAACUGAGUAGA 18

3702 22584

CFTR- IntronlO- + CUGACUAAAACUGAGUAGA 19

3703 22585

CFTR-

+ ACUGACUAAAACUGAGUAGA 20

lntronlO-374 19260

CFTR- IntronlO- + UACUGACUAAAACUGAGUAGA 21

3704 22586

CFTR- IntronlO- + CUACUGACUAAAACUGAGUAGA 22

3705 22587

846

5535.1 CFTR- IntronlO- + ACUACUGACUAAAACUGAGUAGA 23

3706 22588

CFTR- IntronlO- + UACUACUGACUAAAACUGAGUAGA 24

3707 22589

CFTR- IntronlO- + GCACUCCAGCCUGGGCGA 18

3708 22590

CFTR- IntronlO- + UGCACUCCAGCCUGGGCGA 19

3709 22591

CFTR- IntronlO- + CUGCACUCCAGCCUGGGCGA 20

3710 22592

CFTR- IntronlO- + ACUGCACUCCAGCCUGGGCGA 21

3711 22593

CFTR- IntronlO- + CACUGCACUCCAGCCUGGGCGA 22

3712 22594

CFTR- IntronlO- + CCACUGCACUCCAGCCUGGGCGA 23

3713 22595

CFTR- IntronlO- + GCCACUGCACUCCAGCCUGGGCGA 24

3714 22596

CFTR- IntronlO- + UGACUUCAUAAUAAAGGA 18

3715 22597

CFTR- IntronlO- + GUGACUUCAUAAUAAAGGA 19

3716 22598

CFTR- IntronlO- + AGUGACUUCAUAAUAAAGGA 20

3717 22599

CFTR- IntronlO- + CAGUGACUUCAUAAUAAAGGA 21

3718 22600

CFTR- IntronlO- + ACAGUGACUUCAUAAUAAAGGA 22

3719 22601

847

5535.1 CFTR- IntronlO- + UACAGUGACUUCAUAAUAAAGGA 23

3720 22602

CFTR- IntronlO- + AUACAGUGACUUCAUAAUAAAGGA 24

3721 22603

CFTR- IntronlO- + AUGCAGACAACAGAAGGA 18

3722 22604

CFTR- IntronlO- + GAUGCAGACAACAGAAGGA 19

3723 22605

CFTR- IntronlO- + UGAUGCAGACAACAGAAGGA 20

3724 22606

CFTR- IntronlO- + GUG AUGCAGACAACAGAAGGA 21

3725 22607

CFTR- IntronlO- + UGUGAUGCAGACAACAGAAGGA 22

3726 22608

CFTR- IntronlO- + CUGUGAUGCAGACAACAGAAGGA 23

3727 22609

CFTR- IntronlO- + GCUGUGAUGCAGACAACAGAAGGA 24

3728 22610

CFTR- IntronlO- + UAAAACUGAGUAGAAGGA 18

3729 22611

CFTR- IntronlO- + CUAAAACUGAGUAGAAGGA 19

3730 22612

CFTR- IntronlO- + ACUAAAACUGAGUAGAAGGA 20

3731 22613

CFTR- IntronlO- + GACUAAAACUGAGUAGAAGGA 21

3732 22614

CFTR- IntronlO- + UGACUAAAACUGAGUAGAAGGA 22

3733 22615

848

5535.1 CFTR- IntronlO- + CUGACUAAAACUGAGUAGAAGGA 23

3734 22616

CFTR- IntronlO- + ACUGACUAAAACUGAGUAGAAGGA 24

3735 22617

CFTR- IntronlO- + UGUAGGAAAACAACUGGA 18

3736 22618

CFTR- IntronlO- + AUGUAGGAAAACAACUGGA 19

3737 22619

CFTR- IntronlO- + UAUGUAGGAAAACAACUGGA 20

3738 22620

CFTR- IntronlO- + GU AUGUAGGAAAACAACUGGA 21

3739 22621

CFTR- IntronlO- + CGUAUGUAGGAAAACAACUGGA 22

3740 22622

CFTR- IntronlO- + UCGUAUGUAGGAAAACAACUGGA 23

3741 22623

CFTR- IntronlO- + UUCGUAUGUAGGAAAACAACUGGA 24

3742 22624

CFTR- IntronlO- + AAUAUGCAAUUUACUGGA 18

3743 22625

CFTR- IntronlO- + CAAUAUGCAAUUUACUGGA 19

3744 22626

CFTR- IntronlO- + GCAAUAUGCAAUUUACUGGA 20

3745 22627

CFTR- IntronlO- + UGCAAUAUGCAAUUUACUGGA 21

3746 22628

CFTR- IntronlO- + CUGCAAUAUGCAAUUUACUGGA 22

3747 22629

849

5535.1 CFTR- IntronlO- + ACUGCAAUAUGCAAUUUACUGGA 23

3748 22630

CFTR- IntronlO- + UACUGCAAUAUGCAAUUUACUGGA 24

3749 22631

CFTR- IntronlO- + UUUCAUCUUACUUGAUGA 18

3750 22632

CFTR- IntronlO- + GUUUCAUCUUACUUGAUGA 19

3751 22633

CFTR- IntronlO- + AGUUUCAUCUUACUUGAUGA 20

3752 22634

CFTR- IntronlO- + CAGUUUCAUCUUACUUGAUGA 21

3753 22635

CFTR- IntronlO- + ACAGUUUCAUCUUACUUGAUGA 22

3754 22636

CFTR- IntronlO- + AACAGUUUCAUCUUACUUGAUGA 23

3755 22637

CFTR- IntronlO- + UAACAGUUUCAUCUUACUUGAUGA 24

3756 22638

CFTR- IntronlO- + U G ACACCAAAU U U AU UG A 18

3757 22639

CFTR- IntronlO- + CUGACACCAAAUUUAUUGA 19

3758 22640

CFTR- IntronlO- + CCUGACACCAAAUUUAUUGA 20

3759 22641

CFTR- IntronlO- + GCCUGACACCAAAUUUAUUGA 21

3760 22642

CFTR- IntronlO- + AGCCUGACACCAAAUUUAUUGA 22

3761 22643

850

5535.1 CFTR- IntronlO- + CAGCCUGACACCAAAUUUAUUGA 23

3762 22644

CFTR- IntronlO- + CCAGCCUGACACCAAAUUUAUUGA 24

3763 22645

CFTR- IntronlO- + CUAAUAGCCUAUUGUUGA 18

3764 22646

CFTR- IntronlO- + ACUAAUAGCCUAUUGUUGA 19

3765 22647

CFTR- IntronlO- + UACUAAUAGCCUAUUGUUGA 20

3766 22648

CFTR- IntronlO- + CUACUAAUAGCCUAUUGUUGA 21

3767 22649

CFTR- IntronlO- + ACUACUAAUAGCCUAUUGUUGA 22

3768 22650

CFTR- IntronlO- + AACUACUAAUAGCCUAUUGUUGA 23

3769 22651

CFTR- IntronlO- + UAACUACUAAUAGCCUAUUGUUGA 24

3770 22652

CFTR- IntronlO- + CCUUGGAAUAUAAAAAUA 18

3771 22653

CFTR- IntronlO- + UCCUUGGAAUAUAAAAAUA 19

3772 22654

CFTR- IntronlO- + GUCCUUGGAAUAUAAAAAUA 20

3773 22655

CFTR- IntronlO- + AGUCCUUGGAAUAUAAAAAUA 21

3774 22656

CFTR- IntronlO- + CAGUCCUUGGAAUAUAAAAAUA 22

3775 22657

851

5535.1 CFTR- IntronlO- + ACAGUCCUUGGAAUAUAAAAAUA 23

3776 22658

CFTR- IntronlO- + GACAGUCCUUGGAAUAUAAAAAUA 24

3777 22659

CFTR- IntronlO- + CUUUGUGUUAACAAAAUA 18

3778 22660

CFTR- IntronlO- + UCUUUGUGUUAACAAAAUA 19

3779 22661

CFTR- IntronlO- + UUCUUUGUGUUAACAAAAUA 20

3780 22662

CFTR- IntronlO- + GUUCUUUGUGUUAACAAAAUA 21

3781 22663

CFTR- IntronlO- + UGUUCUUUGUGUUAACAAAAUA 22

3782 22664

CFTR- IntronlO- + UUGUUCUUUGUGUUAACAAAAUA 23

3783 22665

CFTR- IntronlO- + GUUGUUCUUUGUGUUAACAAAAUA 24

3784 22666

CFTR- IntronlO- + GGAAGAAAAGUAUCAAUA 18

3785 22667

CFTR- IntronlO- + AGGAAGAAAAGUAUCAAUA 19

3786 22668

CFTR- IntronlO- + C AG G A AG A A A AG U A U C A A U A 20

3787 22669

CFTR- IntronlO- + U C AG G A AG A A A AG U A U C A A U A 21

3788 22670

CFTR- IntronlO- + A U C AG G A AG A A A AG U A U C A A U A 22

3789 22671

852

5535.1 CFTR- IntronlO- + AAUCAGGAAGAAAAGUAUCAAUA 23

3790 22672

CFTR- IntronlO- + UAAUCAGGAAGAAAAGUAUCAAUA 24

3791 22673

CFTR- IntronlO- + UCCUCUGUGCUUUGAAUA 18

3792 22674

CFTR- IntronlO- + GUCCUCUGUGCUUUGAAUA 19

3793 22675

CFTR-

+ AGUCCUCUGUGCUUUGAAUA 20

lntronlO-382 19268

CFTR- IntronlO- + AAGUCCUCUGUGCUUUGAAUA 21

3794 22676

CFTR- IntronlO- + CAAGUCCUCUGUGCUUUGAAUA 22

3795 22677

CFTR- IntronlO- + GCAAGUCCUCUGUGCUUUGAAUA 23

3796 22678

CFTR- IntronlO- + UGCAAGUCCUCUGUGCUUUGAAUA 24

3797 22679

CFTR- IntronlO- + UACAGUGACUUCAUAAUA 18

3798 22680

CFTR- IntronlO- + AUACAGUGACUUCAUAAUA 19

3799 22681

CFTR- IntronlO- + AAUACAGUGACUUCAUAAUA 20

3800 22682

CFTR- IntronlO- + CAAUACAGUGACUUCAUAAUA 21

3801 22683

CFTR- IntronlO- + ACAAUACAGUGACUUCAUAAUA 22

3802 22684

CFTR-

+ GACAAUACAGUGACUUCAUAAUA 23

IntronlO- 22685

853

5535.1 3803

CFTR- IntronlO- + AGACAAUACAGUGACUUCAUAAUA 24

3804 22686

CFTR- IntronlO- + CCUAGAUGAUUAUUAAUA 18

3805 22687

CFTR- IntronlO- + GCCUAGAUGAUUAUUAAUA 19

3806 22688

CFTR-

+ AGCCUAGAUGAUUAUUAAUA 20

lntronlO-384 19270

CFTR- IntronlO- + CAGCCUAGAUGAUUAUUAAUA 21

3807 22689

CFTR- IntronlO- + GCAGCCUAGAUGAUUAUUAAUA 22

3808 22690

CFTR- IntronlO- + UGCAGCCUAGAUGAUUAUUAAUA 23

3809 22691

CFTR- IntronlO- + UUGCAGCCUAGAUGAUUAUUAAUA 24

3810 22692

CFTR- IntronlO- + UAGUAUAAUUUUUUAAUA 18

3811 22693

CFTR- IntronlO- + AUAGUAUAAUUUUUUAAUA 19

3812 22694

CFTR- IntronlO- + UAUAGUAUAAUUUUUUAAUA 20

3813 22695

CFTR- IntronlO- + CUAUAGUAUAAUUUUUUAAUA 21

3814 22696

CFTR- IntronlO- + CCUAUAGUAUAAUUUUUUAAUA 22

3815 22697

CFTR- IntronlO- + UCCUAUAGUAUAAUUUUUUAAUA 23

3816 22698

854

5535.1 CFTR- IntronlO- + CUCCUAUAGUAUAAUUUUUUAAUA 24

3817 22699

CFTR- IntronlO- + UGAAACAAAUAAAACAUA 18

3818 22700

CFTR- IntronlO- + AUGAAACAAAUAAAACAUA 19

3819 22701

CFTR- IntronlO- + AAUGAAACAAAUAAAACAUA 20

3820 22702

CFTR- IntronlO- + AAAUGAAACAAAUAAAACAUA 21

3821 22703

CFTR- IntronlO- + GAAAUGAAACAAAUAAAACAUA 22

3822 22704

CFTR- IntronlO- + AGAAAUGAAACAAAUAAAACAUA 23

3823 22705

CFTR- IntronlO- + AAGAAAUGAAACAAAUAAAACAUA 24

3824 22706

CFTR- IntronlO- + CUAAAACUCAGUACCAUA 18

3825 22707

CFTR- IntronlO- + GCUAAAACUCAGUACCAUA 19

3826 22708

CFTR- IntronlO- + AGCUAAAACUCAGUACCAUA 20

3827 22709

CFTR- IntronlO- + AAGCUAAAACUCAGUACCAUA 21

3828 22710

CFTR- IntronlO- + UAAGCUAAAACUCAGUACCAUA 22

3829 22711

CFTR- IntronlO- + AUAAGCUAAAACUCAGUACCAUA 23

3830 22712

855

5535.1 CFTR- IntronlO- + AAUAAGCUAAAACUCAGUACCAUA 24

3831 22713

CFTR- IntronlO- + AAAAUAUAUAUAUGCAUA 18

3832 22714

CFTR- IntronlO- + AAAAAUAUAUAUAUGCAUA 19

3833 22715

CFTR- IntronlO- + UAAAAAUAUAUAUAUGCAUA 20

3834 22716

CFTR- IntronlO- + UUAAAAAUAUAUAUAUGCAUA 21

3835 22717

CFTR- IntronlO- + GU UAAAAAUAUAUAUAUGCAUA 22

3836 22718

CFTR- IntronlO- + GGUUAAAAAUAUAUAUAUGCAUA 23

3837 22719

CFTR- IntronlO- + AGGUUAAAAAUAUAUAUAUGCAUA 24

3838 22720

CFTR- IntronlO- + ACAUAGAGAAAACUCAUA 18

3839 22721

CFTR- IntronlO- + AACAUAGAGAAAACUCAUA 19

3840 22722

CFTR- IntronlO- + AAACAUAGAGAAAACUCAUA 20

1168 20053

CFTR- IntronlO- + AAAACAUAGAGAAAACUCAUA 21

3841 22723

CFTR- IntronlO- + UAAAACAUAGAGAAAACUCAUA 22

3842 22724

CFTR- IntronlO- + AUAAAACAUAGAGAAAACUCAUA 23

3843 22725

856

5535.1 CFTR- IntronlO- + AAUAAAACAUAGAGAAAACUCAUA 24

3844 22726

CFTR- IntronlO- + GGAAAGUUGUCCAAGAUA 18

3845 22727

CFTR- IntronlO- + UGGAAAGUUGUCCAAGAUA 19

3846 22728

CFTR- IntronlO- + AUGGAAAGUUGUCCAAGAUA 20

3847 22729

CFTR- IntronlO- + UAUGGAAAGUUGUCCAAGAUA 21

3848 22730

CFTR- IntronlO- + AUAUGGAAAGUUGUCCAAGAUA 22

3849 22731

CFTR- IntronlO- + AAUAUGGAAAGUUGUCCAAGAUA 23

3850 22732

CFTR- IntronlO- + GAAUAUGGAAAGUUGUCCAAGAUA 24

3851 22733

CFTR- IntronlO- + UGUUCUUAGGGUGGGAUA 18

3852 22734

CFTR- IntronlO- + UUGUUCUUAGGGUGGGAUA 19

3853 22735

CFTR-

+ GU UGUUCUUAGGGUGGGAUA 20

lntronlO-84 18970

CFTR- IntronlO- + AGUUGUUCUUAGGGUGGGAUA 21

3854 22736

CFTR- IntronlO- + AAGUUGUUCUUAGGGUGGGAUA 22

3855 22737

CFTR- IntronlO- + UAAGUUGUUCUUAGGGUGGGAUA 23

3856 22738

CFTR-

+ UUAAGUUGUUCUUAGGGUGGGAUA 24

IntronlO- 22739

857

5535.1 3857

CFTR- IntronlO- + AUAUUGAUUAUAUAUAUA 18

3858 22740

CFTR- IntronlO- + UAUAUUGAUUAUAUAUAUA 19

3859 22741

CFTR- IntronlO- + GUAUAUUGAUUAUAUAUAUA 20

3860 22742

CFTR- IntronlO- + UGUAUAUUGAUUAUAUAUAUA 21

3861 22743

CFTR- IntronlO- + AUGUAUAUUGAUUAUAUAUAUA 22

3862 22744

CFTR- IntronlO- + AAUGUAUAUUGAUUAUAUAUAUA 23

3863 22745

CFTR- IntronlO- + AAAUGUAUAUUGAUUAUAUAUAUA 24

3864 22746

CFTR- IntronlO- + GUAUAUUGAUUAUAUAUA 18

3865 22747

CFTR- IntronlO- + UGUAUAUUGAUUAUAUAUA 19

3866 22748

CFTR- IntronlO- + AUGUAUAUUGAUUAUAUAUA 20

3867 22749

CFTR- IntronlO- + AAUGUAUAUUGAUUAUAUAUA 21

3868 22750

CFTR- IntronlO- + AAAUGUAUAUUGAUUAUAUAUA 22

3869 22751

CFTR- IntronlO- + AAAAUGUAUAUUGAUUAUAUAUA 23

3870 22752

CFTR-

+ AAAAAUGUAUAUUGAUUAUAUAUA 24

IntronlO- 22753

858

5535.1 3871

CFTR- IntronlO- + CUAGGAUCACUUUAUAUA 18

3872 22754

CFTR- IntronlO- + UCUAGGAUCACUUUAUAUA 19

3873 22755

CFTR- IntronlO- + UUCUAGGAUCACUUUAUAUA 20

3874 22756

CFTR- IntronlO- + AUUCUAGGAUCACUUUAUAUA 21

3875 22757

CFTR- IntronlO- + GAUUCUAGGAUCACUUUAUAUA 22

3876 22758

CFTR- IntronlO- + UGAUUCUAGGAUCACUUUAUAUA 23

3877 22759

CFTR- IntronlO- + AUGAUUCUAGGAUCACUUUAUAUA 24

3878 22760

CFTR- IntronlO- + CCUGAAAGCAGUGUUAUA 18

3879 22761

CFTR- IntronlO- + UCCUGAAAGCAGUGUUAUA 19

3880 22762

CFTR- IntronlO- + CUCCUGAAAGCAGUGUUAUA 20

3881 22763

CFTR- IntronlO- + GCUCCUGAAAGCAGUGUUAUA 21

3882 22764

CFTR- IntronlO- + GGCUCCUGAAAGCAGUGUUAUA 22

3883 22765

CFTR- IntronlO- + UGGCUCCUGAAAGCAGUGUUAUA 23

3884 22766

CFTR-

+ UUGGCUCCUGAAAGCAGUGUUAUA 24

IntronlO- 22767

859

5535.1 3885

CFTR- IntronlO- + UUCUAGGAUCACUUUAUA 18

3886 22768

CFTR- IntronlO- + AUUCUAGGAUCACUUUAUA 19

3887 22769

CFTR- IntronlO- + GAUUCUAGGAUCACUUUAUA 20

3888 22770

CFTR- IntronlO- + UGAUUCUAGGAUCACUUUAUA 21

3889 22771

CFTR- IntronlO- + AUGAUUCUAGGAUCACUUUAUA 22

3890 22772

CFTR- IntronlO- + UAUGAUUCUAGGAUCACUUUAUA 23

3891 22773

CFTR- IntronlO- + UUAUGAUUCUAGGAUCACUUUAUA 24

3892 22774

CFTR- IntronlO- + GACAGAUGAGAGACAGUA 18

3893 22775

CFTR- IntronlO- + GGACAGAUGAGAGACAGUA 19

3894 22776

CFTR- IntronlO- + UGGACAGAUGAGAGACAGUA 20

3895 22777

CFTR- IntronlO- + AUGGACAGAUGAGAGACAGUA 21

3896 22778

CFTR- IntronlO- + AAUGGACAGAUGAGAGACAGUA 22

3897 22779

CFTR- IntronlO- + AAAUGGACAGAUGAGAGACAGUA 23

3898 22780

CFTR-

+ AAAAUGGACAGAUGAGAGACAGUA 24

IntronlO- 22781

860

5535.1 3899

CFTR- IntronlO- + UUUCUAGAAAACAAUGUA 18

3900 22782

CFTR- IntronlO- + UUUUCUAGAAAACAAUGUA 19

3901 22783

CFTR- IntronlO- + AUUUUCUAGAAAACAAUGUA 20

3902 22784

CFTR- IntronlO- + GAUUUUCUAGAAAACAAUGUA 21

3903 22785

CFTR- IntronlO- + AGAUUUUCUAGAAAACAAUGUA 22

3904 22786

CFTR- IntronlO- + CAG AU U U U CU AG AAAACAAUG U A 23

3905 22787

CFTR- IntronlO- + ACAG AU U U U CU AG AAAACAAUG U A 24

3906 22788

CFTR- IntronlO- + GUAUAAGUGUGGAGUGUA 18

3907 22789

CFTR- IntronlO- + GGUAUAAGUGUGGAGUGUA 19

3908 22790

CFTR- IntronlO- + GGGUAUAAGUGUGGAGUGUA 20

3909 22791

CFTR- IntronlO- + GGGGUAUAAGUGUGGAGUGUA 21

3910 22792

CFTR- IntronlO- + UGGGGUAUAAGUGUGGAGUGUA 22

3911 22793

CFTR- IntronlO- + AUGGGGUAUAAGUGUGGAGUGUA 23

3912 22794

CFTR-

+ AAUGGGGUAUAAGUGUGGAGUGUA 24

IntronlO- 22795

861

5535.1 3913

CFTR- IntronlO- + UUCUUGAAG C A A A A A U U A 18

3914 22796

CFTR- IntronlO- + AUUCUUGAAGCAAAAAUUA 19

3915 22797

CFTR- IntronlO- + UAUUCUUGAAGCAAAAAUUA 20

3916 22798

CFTR- IntronlO- + AUAUUCUUGAAGCAAAAAUUA 21

3917 22799

CFTR- IntronlO- + AAU AU U CU UG AAGCAAAAAU U A 22

3918 22800

CFTR- IntronlO- + CAAU AU U CU UG AAG CAAAAAU U A 23

3919 22801

CFTR- IntronlO- + GCAAUAUUCUUGAAGCAAAAAUUA 24

3920 22802

CFTR- IntronlO- + CUGAAU AACACGCCAU U A 18

3921 22803

CFTR- IntronlO- + GCUGAAUAACACGCCAUUA 19

3922 22804

CFTR- IntronlO- + GGCUGAAUAACACGCCAUUA 20

3923 22805

CFTR- IntronlO- + UGGCUGAAUAACACGCCAUUA 21

3924 22806

CFTR- IntronlO- + UUGGCUGAAUAACACGCCAUUA 22

3925 22807

CFTR- IntronlO- + AUUGGCUGAAUAACACGCCAUUA 23

3926 22808

CFTR-

+ UAUUGGCUGAAUAACACGCCAUUA 24

IntronlO- 22809

862

5535.1 3927

CFTR- IntronlO- + UUAUCAGAGCUCAUAUUA 18

3928 22810

CFTR- IntronlO- + UUUAUCAGAGCUCAUAUUA 19

3929 22811

CFTR- IntronlO- + UUUUAUCAGAGCUCAUAUUA 20

3930 22812

CFTR- IntronlO- + AUUUUAUCAGAGCUCAUAUUA 21

3931 22813

CFTR- IntronlO- + GAUUUUAUCAGAGCUCAUAUUA 22

3932 22814

CFTR- IntronlO- + UGAUUUUAUCAGAGCUCAUAUUA 23

3933 22815

CFTR- IntronlO- + CUGAUUUUAUCAGAGCUCAUAUUA 24

3934 22816

CFTR- IntronlO- + CAAAUGCUUGACCACUUA 18

3935 22817

CFTR- IntronlO- + ACAAAUGCUUGACCACUUA 19

3936 22818

CFTR- IntronlO- + CACAAAUGCUUGACCACUUA 20

3937 22819

CFTR- IntronlO- + ACA CAAAUGCUUGACCACUUA 21

3938 22820

CFTR- IntronlO- + UACACAAAUGCUUGACCACUUA 22

3939 22821

CFTR- IntronlO- + GUACACAAAUGCUUGACCACUUA 23

3940 22822

CFTR-

+ AGUACACAAAUGCUUGACCACUUA 24

IntronlO- 22823

863

5535.1 3941

CFTR- IntronlO- + AU U AAU AACAAAAU CU U A 18

3942 22824

CFTR- IntronlO- + U AU U AAU AACAAAAU CU U A 19

3943 22825

CFTR- IntronlO- + AUAUUAAUAACAAAAUCUUA 20

3944 22826

CFTR- IntronlO- + AAU AU U AAU AACAAAAU CU U A 21

3945 22827

CFTR- IntronlO- + UAAUAUUAAUAACAAAAUCUUA 22

3946 22828

CFTR- IntronlO- + GUAAUAUUAAUAACAAAAUCUUA 23

3947 22829

CFTR- IntronlO- + AGUAAUAUUAAUAACAAAAUCUUA 24

3948 22830

CFTR- IntronlO- + ACAUAUUUGGGUAAGUUA 18

3949 22831

CFTR- IntronlO- + AACAUAUUUGGGUAAGUUA 19

3950 22832

CFTR- IntronlO- + AAACAUAUUUGGGUAAGUUA 20

3951 22833

CFTR- IntronlO- + CAAACAUAUUUGGGUAAGUUA 21

3952 22834

CFTR- IntronlO- + GCAAACAUAUUUGGGUAAGUUA 22

3953 22835

CFTR- IntronlO- + UGCAAACAUAUUUGGGUAAGUUA 23

3954 22836

CFTR-

+ CUGCAAACAUAUUUGGGUAAGUUA 24

IntronlO- 22837

864

5535.1 3955

CFTR- IntronlO- + ACUGCAAUAUGCAAUUUA 18

3956 22838

CFTR- IntronlO- + UACUGCAAUAUGCAAUUUA 19

3957 22839

CFTR- IntronlO- + UUACUGCAAUAUGCAAUUUA 20

3958 22840

CFTR- IntronlO- + UUUACUGCAAUAUGCAAUUUA 21

3959 22841

CFTR- IntronlO- + UUUUACUGCAAUAUGCAAUUUA 22

3960 22842

CFTR- IntronlO- + UUUUUACUGCAAUAUGCAAUUUA 23

3961 22843

CFTR- IntronlO- + CUUUUUACUGCAAUAUGCAAUUUA 24

3962 22844

CFTR- IntronlO- + CCUAUUAUUCAACAUUUA 18

3963 22845

CFTR- IntronlO- + CCCUAUUAUUCAACAUUUA 19

3964 22846

CFTR-

+ CCCCUAUUAUUCAACAUUUA 20

lntronlO-398 19284

CFTR- IntronlO- + ACCCCUAUUAUUCAACAUUUA 21

3965 22847

CFTR- IntronlO- + AACCCCUAUUAUUCAACAUUUA 22

3966 22848

CFTR- IntronlO- + AAACCCCUAUUAUUCAACAUUUA 23

3967 22849

CFTR- IntronlO- + CAAACCCCU AU U AU U CAACAU U U A 24

3968 22850

865

5535.1 CFTR- IntronlO- + U A A A A AG C A AG C A A A A AC 18

3969 22851

CFTR- IntronlO- + AUAAAAAG CAAG CAAAAAC 19

3970 22852

CFTR- IntronlO- + U A U A A A A AG C A AG C A A A A AC 20

3971 22853

CFTR- IntronlO- + GUAUAAAAAGCAAGCAAAAAC 21

3972 22854

CFTR- IntronlO- + U G U A U A A A A AG CAAG CAAAAAC 22

3973 22855

CFTR- IntronlO- + C U G U A U A A A A AG CAAG CAAAAAC 23

3974 22856

CFTR- IntronlO- + UCUGUAUAAAAAGCAAGCAAAAAC 24

3975 22857

CFTR- IntronlO- + AACAUCUAACUCAAAAAC 18

3976 22858

CFTR- IntronlO- + AAACAUCUAACUCAAAAAC 19

3977 22859

CFTR- IntronlO- + CAAACAUCUAACUCAAAAAC 20

3978 22860

CFTR- IntronlO- + UCAAACAUCUAACUCAAAAAC 21

3979 22861

CFTR- IntronlO- + GUCAAACAUCUAACUCAAAAAC 22

3980 22862

CFTR- IntronlO- + CG U CA AACAU C U AAC U CAAAAAC 23

3981 22863

CFTR- IntronlO- + GCGUCAAACAUCUAACUCAAAAAC 24

3982 22864

866

5535.1 CFTR- IntronlO- + CGUAUGUAGGAAAACAAC 18

3983 22865

CFTR- IntronlO- + UCGUAUGUAGGAAAACAAC 19

3984 22866

CFTR-

+ UUCGUAUGUAGGAAAACAAC 20

lntronlO-402 19288

CFTR- IntronlO- + UUUCGUAUGUAGGAAAACAAC 21

3985 22867

CFTR- IntronlO- + GUUUCGUAUGUAGGAAAACAAC 22

3986 22868

CFTR- IntronlO- + UGUUUCGUAUGUAGGAAAACAAC 23

3987 22869

CFTR- IntronlO- + CUGUUUCGUAUGUAGGAAAACAAC 24

3988 22870

CFTR- IntronlO- + GCUUACCGUAAUAGCAAC 18

3989 22871

CFTR- IntronlO- + AGCUUACCGUAAUAGCAAC 19

3990 22872

CFTR-

+ GAGCUUACCGUAAUAGCAAC 20

lntronlO-660 19546

CFTR- IntronlO- + UGAGCUUACCGUAAUAGCAAC 21

3991 22873

CFTR- IntronlO- + UUGAGCUUACCGUAAUAGCAAC 22

3992 22874

CFTR- IntronlO- + CUUGAGCUUACCGUAAUAGCAAC 23

3993 22875

CFTR- IntronlO- + GCUUGAGCUUACCGUAAUAGCAAC 24

3994 22876

CFTR- IntronlO- + CAUUGACCCUUUAUCAAC 18

3995 22877

867

5535.1 CFTR- IntronlO- + CCAUUGACCCUUUAUCAAC 19

3996 22878

CFTR- IntronlO- + ACCAUUGACCCUUUAUCAAC 20

3997 22879

CFTR- IntronlO- + UACCAUUGACCCUUUAUCAAC 21

3998 22880

CFTR- IntronlO- + AUACCAUUGACCCUUUAUCAAC 22

3999 22881

CFTR- IntronlO- + UAUACCAUUGACCCUUUAUCAAC 23

4000 22882

CFTR- IntronlO- + AUAUACCAUUGACCCUUUAUCAAC 24

4001 22883

CFTR- IntronlO- + UGACAAUCAAAUGGGAAC 18

4002 22884

CFTR- IntronlO- + AUGACAAUCAAAUGGGAAC 19

4003 22885

CFTR- IntronlO- + AAUGACAAUCAAAUGGGAAC 20

4004 22886

CFTR- IntronlO- + AAAUGACAAUCAAAUGGGAAC 21

4005 22887

CFTR- IntronlO- + AAAAUGACAAUCAAAUGGGAAC 22

4006 22888

CFTR- IntronlO- + UAAAAUGACAAUCAAAUGGGAAC 23

4007 22889

CFTR- IntronlO- + CUAAAAUGACAAUCAAAUGGGAAC 24

4008 22890

CFTR- IntronlO- + CAGGAGAAUGGCGUGAAC 18

4009 22891

868

5535.1 CFTR- IntronlO- + GCAGGAGAAUGGCGUGAAC 19

4010 22892

CFTR- IntronlO- + GGCAGGAGAAUGGCGUGAAC 20

4011 22893

CFTR- IntronlO- + AGGCAGGAGAAUGGCGUGAAC 21

4012 22894

CFTR- IntronlO- + GAGGCAGGAGAAUGGCGUGAAC 22

4013 22895

CFTR- IntronlO- + UGAGGCAGGAGAAUGGCGUGAAC 23

4014 22896

CFTR- IntronlO- + CUGAGGCAGGAGAAUGGCGUGAAC 24

4015 22897

CFTR- IntronlO- + GAACCUAUAAGGAAUAAC 18

4016 22898

CFTR- IntronlO- + AGAACCUAUAAGGAAUAAC 19

4017 22899

CFTR-

+ CAGAACCUAUAAGGAAUAAC 20

lntronlO-403 19289

CFTR- IntronlO- + ACAGAACCUAUAAGGAAUAAC 21

4018 22900

CFTR- IntronlO- + UACAGAACCUAUAAGGAAUAAC 22

4019 22901

CFTR- IntronlO- + U UACAGAACCUAUAAGGAAUAAC 23

4020 22902

CFTR- IntronlO- + AUUACAGAACCUAUAAGGAAUAAC 24

4021 22903

CFTR- IntronlO- + AAAAUAUGCGAGAACCAC 18

4022 22904

CFTR-

+ AAAAAUAUGCGAGAACCAC 19

IntronlO- 22905

869

5535.1 4023

CFTR- IntronlO- + GAAAAAUAUGCGAGAACCAC 20

4024 22906

CFTR- IntronlO- + UGAAAAAUAUGCGAGAACCAC 21

4025 22907

CFTR- IntronlO- + AUGAAAAAUAUGCGAGAACCAC 22

4026 22908

CFTR- IntronlO- + GAUGAAAAAUAUGCGAGAACCAC 23

4027 22909

CFTR- IntronlO- + UGAUGAAAAAUAUGCGAGAACCAC 24

4028 22910

CFTR- IntronlO- + AGUAUUAAGUAUAGCCAC 18

4029 22911

CFTR- IntronlO- + UAGUAUUAAGUAUAGCCAC 19

4030 22912

CFTR-

+ UUAGUAUUAAGUAUAGCCAC 20

lntronlO-408 19294

CFTR- IntronlO- + AUUAGUAUUAAGUAUAGCCAC 21

4031 22913

CFTR- IntronlO- + UAUUAGUAUUAAGUAUAGCCAC 22

4032 22914

CFTR- IntronlO- + UUAUUAGUAUUAAGUAUAGCCAC 23

4033 22915

CFTR- IntronlO- + GUUAUUAGUAUUAAGUAUAGCCAC 24

4034 22916

CFTR- IntronlO- + UUUAAUAAAUAAUAUCAC 18

4035 22917

CFTR- IntronlO- + UUUUAAUAAAUAAUAUCAC 19

4036 22918

870

5535.1 CFTR- IntronlO- + AU U U U AAU AAAU AAU AU CAC 20

4037 22919

CFTR- IntronlO- + AAU U U U AAU AAAU AAU AU CAC 21

4038 22920

CFTR- IntronlO- + AAAU U U U AAU AAAU AAU AU CAC 22

4039 22921

CFTR- IntronlO- + U AAAU U U U AAU AAAU AAU AU CAC 23

4040 22922

CFTR- IntronlO- + U U AAAU U U U AAU AAAU AAU AU CAC 24

4041 22923

CFTR- IntronlO- + GGAGAGAGAACUGCUCAC 18

4042 22924

CFTR- IntronlO- + UGGAGAGAGAACUGCUCAC 19

4043 22925

CFTR- IntronlO- + CUGGAGAGAGAACUGCUCAC 20

4044 22926

CFTR- IntronlO- + ACUGGAGAGAGAACUGCUCAC 21

4045 22927

CFTR- IntronlO- + UACUGGAGAGAGAACUGCUCAC 22

4046 22928

CFTR- IntronlO- + UUACUGGAGAGAGAACUGCUCAC 23

4047 22929

CFTR- IntronlO- + UUUACUGGAGAGAGAACUGCUCAC 24

4048 22930

CFTR- IntronlO- + AAGACAUUUAAUGUAGAC 18

4049 22931

CFTR- IntronlO- + CAAG ACAU U U AAUG U AG AC 19

4050 22932

871

5535.1 CFTR- IntronlO- + GCAAGACAUUUAAUGUAGAC 20

4051 22933

CFTR- IntronlO- + CGCAAGACAUUUAAUGUAGAC 21

4052 22934

CFTR- IntronlO- + GCGCAAGACAUUUAAUGUAGAC 22

4053 22935

CFTR- IntronlO- + AGCGCAAGACAUUUAAUGUAGAC 23

4054 22936

CFTR- IntronlO- + AAGCGCAAGACAUUUAAUGUAGAC 24

4055 22937

CFTR- IntronlO- + UUUAGCCCAUUCUAAUAC 18

4056 22938

CFTR- IntronlO- + CUUUAGCCCAUUCUAAUAC 19

4057 22939

CFTR- IntronlO- + CCUUUAGCCCAUUCUAAUAC 20

4058 22940

CFTR- IntronlO- + CCCUUUAGCCCAUUCUAAUAC 21

4059 22941

CFTR- IntronlO- + GCCCUUUAGCCCAUUCUAAUAC 22

4060 22942

CFTR- IntronlO- + UGCCCUUUAGCCCAUUCUAAUAC 23

4061 22943

CFTR- IntronlO- + UUGCCCUUUAGCCCAUUCUAAUAC 24

4062 22944

CFTR- IntronlO- + UAUUUGUGGAGGACAUAC 18

4063 22945

CFTR- IntronlO- + AUAUUUGUGGAGGACAUAC 19

4064 22946

872

5535.1 CFTR- IntronlO- + AAUAUUUGUGGAGGACAUAC 20

4065 22947

CFTR- IntronlO- + AAAUAUUUGUGGAGGACAUAC 21

4066 22948

CFTR- IntronlO- + AAAAUAUUUGUGGAGGACAUAC 22

4067 22949

CFTR- IntronlO- + AAAAAUAUUUGUGGAGGACAUAC 23

4068 22950

CFTR- IntronlO- + AAAAAAUAUUUGUGGAGGACAUAC 24

4069 22951

CFTR- IntronlO- + GCCUGUAGUCCCAGCUAC 18

4070 22952

CFTR- IntronlO- + CGCCUGUAGUCCCAGCUAC 19

4071 22953

CFTR- IntronlO- + GCGCCUGUAGUCCCAGCUAC 20

4072 22954

CFTR- IntronlO- + GGCGCCUGUAGUCCCAGCUAC 21

4073 22955

CFTR- IntronlO- + GGGCGCCUGUAGUCCCAGCUAC 22

4074 22956

CFTR- IntronlO- + CGGGCGCCUGUAGUCCCAGCUAC 23

4075 22957

CFTR- IntronlO- + GCGGGCGCCUGUAGUCCCAGCUAC 24

4076 22958

CFTR- IntronlO- + UGCCUGUAGUCCCAGCUAC 19

4077 22959

CFTR- IntronlO- + GUGCCUGUAGUCCCAGCUAC 20

4078 22960

873

5535.1 CFTR- IntronlO- + CGUGCCUGUAGUCCCAGCUAC 21

4079 22961

CFTR- IntronlO- + GCGUGCCUGUAGUCCCAGCUAC 22

4080 22962

CFTR- IntronlO- + UGCGUGCCUGUAGUCCCAGCUAC 23

4081 22963

CFTR- IntronlO- + GUGCGUGCCUGUAGUCCCAGCUAC 24

4082 22964

CFTR- IntronlO- + ACUUGCUUCACCUGCUAC 18

4083 22965

CFTR- IntronlO- + CACUUGCUUCACCUGCUAC 19

4084 22966

CFTR- IntronlO- + GCACUUGCUUCACCUGCUAC 20

4085 22967

CFTR- IntronlO- + UGCACUUGCUUCACCUGCUAC 21

4086 22968

CFTR- IntronlO- + UUGCACUUGCUUCACCUGCUAC 22

4087 22969

CFTR- IntronlO- + UUUGCACUUGCUUCACCUGCUAC 23

4088 22970

CFTR- IntronlO- + CUUUGCACUUGCUUCACCUGCUAC 24

4089 22971

CFTR- IntronlO- + AAAUCUUAUAGAGAUUAC 18

4090 22972

CFTR- IntronlO- + AAAAUCUUAUAGAGAUUAC 19

4091 22973

CFTR- IntronlO- + CAAAAU CU U AU AG AG AU U AC 20

4092 22974

874

5535.1 CFTR- IntronlO- + ACAAAAUCUUAUAGAGAUUAC 21

4093 22975

CFTR- IntronlO- + AACAAAAU CU U AU AG AG AU U AC 22

4094 22976

CFTR- IntronlO- + UAACAAAAUCUUAUAGAGAUUAC 23

4095 22977

CFTR- IntronlO- + AUAACAAAAUCUUAUAGAGAUUAC 24

4096 22978

CFTR- IntronlO- + UUUUACAAUUCUUAUUAC 18

4097 22979

CFTR- IntronlO- + AUUUUACAAUUCUUAUUAC 19

4098 22980

CFTR- IntronlO- + AAUUUUACAAUUCUUAUUAC 20

4099 22981

CFTR- IntronlO- + AAAUUUUACAAUUCUUAUUAC 21

4100 22982

CFTR- IntronlO- + UAAAUUUUACAAUUCUUAUUAC 22

4101 22983

CFTR- IntronlO- + GUAAAUUUUACAAUUCUUAUUAC 23

4102 22984

CFTR- IntronlO- + AG U AAAU U U U ACAAU UCUUAUUAC 24

4103 22985

CFTR- IntronlO- + CUGCAAUAUGCAAUUUAC 18

4104 22986

CFTR- IntronlO- + ACUGCAAUAUGCAAUUUAC 19

4105 22987

CFTR- IntronlO- + UACUGCAAUAUGCAAUUUAC 20

1190 20075

875

5535.1 CFTR- IntronlO- + UUACUGCAAUAUGCAAUUUAC 21

4106 22988

CFTR- IntronlO- + UUUACUGCAAUAUGCAAUUUAC 22

4107 22989

CFTR- IntronlO- + UUUUACUGCAAUAUGCAAUUUAC 23

4108 22990

CFTR- IntronlO- + UUUUUACUGCAAUAUGCAAUUUAC 24

4109 22991

CFTR- IntronlO- + U U UG U ACAAAAU U AAACC 18

4110 22992

CFTR- IntronlO- + CU U UG U ACAAAAU U AAACC 19

4111 22993

CFTR- IntronlO- + CCU UUGU ACAAAAU U AAACC 20

4112 22994

CFTR- IntronlO- + UCCUUUGUACAAAAUUAAACC 21

4113 22995

CFTR- IntronlO- + UUCCUUUGUACAAAAUUAAACC 22

4114 22996

CFTR- IntronlO- + AUUCCUUUGUACAAAAUUAAACC 23

4115 22997

CFTR- IntronlO- + AAU U CCU U UG U ACAAAAU U AAACC 24

4116 22998

CFTR- IntronlO- + AGGAGAAUGGCGUGAACC 18

4117 22999

CFTR- IntronlO- + CAGGAGAAUGGCGUGAACC 19

4118 23000

CFTR-

+ GCAGGAGAAUGGCGUGAACC 20

lntronlO-661 19547

CFTR-

+ GGCAGGAGAAUGGCGUGAACC 21

IntronlO- 23001

876

5535.1 4119

CFTR- IntronlO- + AGGCAGGAGAAUGGCGUGAACC 22

4120 23002

CFTR- IntronlO- + GAGGCAGGAGAAUGGCGUGAACC 23

4121 23003

CFTR- IntronlO- + UGAGGCAGGAGAAUGGCGUGAACC 24

4122 23004

CFTR- IntronlO- + GGUCUUGAUCUCCUAACC 18

4123 23005

CFTR- IntronlO- + UGGUCUUGAUCUCCUAACC 19

4124 23006

CFTR- IntronlO- + AUGGUCUUGAUCUCCUAACC 20

4125 23007

CFTR- IntronlO- + GAUGGUCUUGAUCUCCUAACC 21

4126 23008

CFTR- IntronlO- + GGAUGGUCUUGAUCUCCUAACC 22

4127 23009

CFTR- IntronlO- + AGGAUGGUCUUGAUCUCCUAACC 23

4128 23010

CFTR- IntronlO- + CAGGAUGGUCUUGAUCUCCUAACC 24

4129 23011

CFTR- IntronlO- + CCCUGCAAUACCAUCACC 18

4130 23012

CFTR- IntronlO- + ACCCUGCAAUACCAUCACC 19

4131 23013

CFTR- IntronlO- + CACCCUGCAAUACCAUCACC 20

4132 23014

CFTR-

+ CCACCCUGCAAUACCAUCACC 21

IntronlO- 23015

877

5535.1 4133

CFTR- IntronlO- + CCCACCCUGCAAUACCAUCACC 22

4134 23016

CFTR- IntronlO- + CCCCACCCUGCAAUACCAUCACC 23

4135 23017

CFTR- IntronlO- + GCCCCACCCUGCAAUACCAUCACC 24

4136 23018

CFTR- IntronlO- + GUGGCCUCUAAUCUCACC 18

4137 23019

CFTR- IntronlO- + AGUGGCCUCUAAUCUCACC 19

4138 23020

CFTR- IntronlO- + CAGUGGCCUCUAAUCUCACC 20

4139 23021

CFTR- IntronlO- + CCAGUGGCCUCUAAUCUCACC 21

4140 23022

CFTR- IntronlO- + UCCAGUGGCCUCUAAUCUCACC 22

4141 23023

CFTR- IntronlO- + CUCCAGUGGCCUCUAAUCUCACC 23

4142 23024

CFTR- IntronlO- + UCUCCAGUGGCCUCUAAUCUCACC 24

4143 23025

CFTR- IntronlO- + CUGCUAUAACAAAAUACC 18

4144 23026

CFTR- IntronlO- + GCUGCUAUAACAAAAUACC 19

4145 23027

CFTR- IntronlO- + GGCUGCUAUAACAAAAUACC 20

4146 23028

CFTR-

+ AGGCUGCUAUAACAAAAUACC 21

IntronlO- 23029

878

5535.1 4147

CFTR- IntronlO- + CAGGCUGCUAUAACAAAAUACC 22

4148 23030

CFTR- IntronlO- + UCAGGCUGCUAUAACAAAAUACC 23

4149 23031

CFTR- IntronlO- + UUCAGGCUGCUAUAACAAAAUACC 24

4150 23032

CFTR- IntronlO- + UACAGCUAAAGUAUUACC 18

4151 23033

CFTR- IntronlO- + AUACAGCUAAAGUAUUACC 19

4152 23034

CFTR- IntronlO- + UAUACAGCUAAAGUAUUACC 20

4153 23035

CFTR- IntronlO- + AUAUACAGCUAAAGUAUUACC 21

4154 23036

CFTR- IntronlO- + AAUAUACAGCUAAAGUAUUACC 22

4155 23037

CFTR- IntronlO- + UAAUAUACAGCUAAAGUAUUACC 23

4156 23038

CFTR- IntronlO- + AUAAUAUACAGCUAAAGUAUUACC 24

4157 23039

CFTR- IntronlO- + GGAGAAUGGCGUGAACCC 18

4158 23040

CFTR- IntronlO- + AGGAGAAUGGCGUGAACCC 19

4159 23041

CFTR- IntronlO- + CAGGAGAAUGGCGUGAACCC 20

1191 20076

CFTR-

+ GCAGGAGAAUGGCGUGAACCC 21

IntronlO- 23042

879

5535.1 4160

CFTR- IntronlO- + GGCAGGAGAAUGGCGUGAACCC 22

4161 23043

CFTR- IntronlO- + AGGCAGGAGAAUGGCGUGAACCC 23

4162 23044

CFTR- IntronlO- + GAGGCAGGAGAAUGGCGUGAACCC 24

4163 23045

CFTR- IntronlO- + GGAGAAUUGCUUGAGCCC 18

4164 23046

CFTR- IntronlO- + AGGAGAAUUGCUUGAGCCC 19

4165 23047

CFTR- IntronlO- + CAGGAGAAUUGCUUGAGCCC 20

1195 20080

CFTR- IntronlO- + GCAGGAGAAUUGCUUGAGCCC 21

4166 23048

CFTR- IntronlO- + GGCAGGAGAAUUGCUUGAGCCC 22

4167 23049

CFTR- IntronlO- + AGGCAGGAGAAUUGCUUGAGCCC 23

4168 23050

CFTR- IntronlO- + GAGGCAGGAGAAUUGCUUGAGCCC 24

4169 23051

CFTR- IntronlO- + AAGUGUUUAAAUAUUCCC 18

4170 23052

CFTR- IntronlO- + GAAGUGUUUAAAUAUUCCC 19

4171 23053

CFTR- IntronlO- + AGAAGUGUUUAAAUAUUCCC 20

4172 23054

CFTR-

+ CAGAAGUGUUUAAAUAUUCCC 21

IntronlO- 23055

880

5535.1 4173

CFTR- IntronlO- + UCAGAAGUGUUUAAAUAUUCCC 22

4174 23056

CFTR- IntronlO- + CUCAGAAGUGUUUAAAUAUUCCC 23

4175 23057

CFTR- IntronlO- + UCUCAGAAGUGUUUAAAUAUUCCC 24

4176 23058

CFTR- IntronlO- + GGAAAGGUCAAUUGAGCC 18

4177 23059

CFTR- IntronlO- + CGGAAAGGUCAAUUGAGCC 19

4178 23060

CFTR- IntronlO- + GCGGAAAGGUCAAUUGAGCC 20

4179 23061

CFTR- IntronlO- + AGCGGAAAGGUCAAUUGAGCC 21

4180 23062

CFTR- IntronlO- + AAGCGGAAAGGUCAAUUGAGCC 22

4181 23063

CFTR- IntronlO- + GAAGCGGAAAGGUCAAUUGAGCC 23

4182 23064

CFTR- IntronlO- + UGAAGCGGAAAGGUCAAUUGAGCC 24

4183 23065

CFTR- IntronlO- + AGGAGAAUUGCUUGAGCC 18

4184 23066

CFTR- IntronlO- + CAGGAGAAUUGCUUGAGCC 19

4185 23067

CFTR-

+ GCAGGAGAAUUGCUUGAGCC 20

lntronlO-665 19551

CFTR- IntronlO- + GGCAGGAGAAUUGCUUGAGCC 21

4186 23068

881

5535.1 CFTR- IntronlO- + AGGCAGGAGAAUUGCUUGAGCC 22

4187 23069

CFTR- IntronlO- + GAGGCAGGAGAAUUGCUUGAGCC 23

4188 23070

CFTR- IntronlO- + UGAGGCAGGAGAAUUGCUUGAGCC 24

4189 23071

CFTR- IntronlO- + GGCACUUGUUGACAGUCC 18

4190 23072

CFTR- IntronlO- + AGGCACUUGUUGACAGUCC 19

4191 23073

CFTR- IntronlO- + UAGGCACUUGUUGACAGUCC 20

4192 23074

CFTR- IntronlO- + CUAGGCACUUGUUGACAGUCC 21

4193 23075

CFTR- IntronlO- + GCUAGGCACUUGUUGACAGUCC 22

4194 23076

CFTR- IntronlO- + UGCUAGGCACUUGUUGACAGUCC 23

4195 23077

CFTR- IntronlO- + GUGCUAGGCACUUGUUGACAGUCC 24

4196 23078

CFTR- IntronlO- + CUACCAGCCCCCUCUUCC 18

4197 23079

CFTR- IntronlO- + ACUACCAGCCCCCUCUUCC 19

4198 23080

CFTR- IntronlO- + CACUACCAGCCCCCUCUUCC 20

4199 23081

CFTR- IntronlO- + ACACUACCAGCCCCCUCUUCC 21

4200 23082

882

5535.1 CFTR- IntronlO- + CACACUACCAGCCCCCUCUUCC 22

4201 23083

CFTR- IntronlO- + UCACACUACCAGCCCCCUCUUCC 23

4202 23084

CFTR- IntronlO- + UUCACACUACCAGCCCCCUCUUCC 24

4203 23085

CFTR- IntronlO- + CAAGAUAGUGGG A A A AG C 18

4204 23086

CFTR- IntronlO- + CCAAGAUAGUGGG A A A AG C 19

4205 23087

CFTR- IntronlO- + UCCAAGAUAGUGGGAAAAGC 20

4206 23088

CFTR- IntronlO- + GUCCAAGAUAGUGGGAAAAGC 21

4207 23089

CFTR- IntronlO- + UGUCCAAGAUAGUGGGAAAAGC 22

4208 23090

CFTR- IntronlO- + UUGUCCAAGAUAGUGGGAAAAGC 23

4209 23091

CFTR- IntronlO- + GUUGUCCAAGAUAGUGGGAAAAGC 24

4210 23092

CFTR- IntronlO- + UUACUCAGUCCAGAAAGC 18

4211 23093

CFTR- IntronlO- + G U U ACU CAG U CCAGAAAG C 19

4212 23094

CFTR- IntronlO- + AGUUACUCAGUCCAGAAAGC 20

4213 23095

CFTR- IntronlO- + CAGUUACUCAGUCCAG A A AG C 21

4214 23096

883

5535.1 CFTR- IntronlO- + CCAGUUACUCAGUCCAGAAAGC 22

4215 23097

CFTR- IntronlO- + U CCAG U U ACU CAG U CCAG AAAG C 23

4216 23098

CFTR- IntronlO- + U U CCAG U U ACU CAG U CCAG AAAGC 24

4217 23099

CFTR- IntronlO- + CCGCCACUGCACUCCAGC 18

4218 23100

CFTR- IntronlO- + CCCGCCACUGCACUCCAGC 19

4219 23101

CFTR- IntronlO- + UCCCGCCACUGCACUCCAGC 20

4220 23102

CFTR- IntronlO- + AUCCCGCCACUGCACUCCAGC 21

4221 23103

CFTR- IntronlO- + GAUCCCGCCACUGCACUCCAGC 22

4222 23104

CFTR- IntronlO- + AGAUCCCGCCACUGCACUCCAGC 23

4223 23105

CFTR- IntronlO- + GAGAUCCCGCCACUGCACUCCAGC 24

4224 23106

CFTR- IntronlO- + CAGGAGAAUUGCUUGAGC 18

4225 23107

CFTR- IntronlO- + GCAGGAGAAUUGCUUGAGC 19

4226 23108

CFTR- IntronlO- + GGCAGGAGAAUUGCUUGAGC 20

4227 23109

CFTR- IntronlO- + AGGCAGGAGAAUUGCUUGAGC 21

4228 23110

884

5535.1 CFTR- IntronlO- + GAGGCAGGAGAAUUGCUUGAGC 22

4229 23111

CFTR- IntronlO- + UGAGGCAGGAGAAUUGCUUGAGC 23

4230 23112

CFTR- IntronlO- + GUGAGGCAGGAGAAUUGCUUGAGC 24

4231 23113

CFTR- IntronlO- + ACCUCAGCCUCCCAAGUAGC 20

1222 20107

CFTR- IntronlO- + CACCUCAGCCUCCCAAGUAGC 21

4232 23114

CFTR- IntronlO- + CCACCUCAGCCUCCCAAGUAGC 22

4233 23115

CFTR- IntronlO- + CCCACCUCAGCCUCCCAAGUAGC 23

4234 23116

CFTR- IntronlO- + UCCCACCUCAGCCUCCCAAGUAGC 24

4235 23117

CFTR- IntronlO- + CUCAGCCUCCCGAGUAGC 18

4236 23118

CFTR- IntronlO- + CCUCAGCCUCCCGAGUAGC 19

4237 23119

CFTR-

+ GCCUCAGCCUCCCGAGUAGC 20

lntronlO-675 19561

CFTR- IntronlO- + UGCCUCAGCCUCCCGAGUAGC 21

4238 23120

CFTR- IntronlO- + CUGCCUCAGCCUCCCGAGUAGC 22

4239 23121

CFTR- IntronlO- + CCUGCCUCAGCCUCCCGAGUAGC 23

4240 23122

CFTR-

+ UCCUGCCUCAGCCUCCCGAGUAGC 24

IntronlO- 23123

885

5535.1 4241

CFTR- IntronlO- + AAACUCAUAAGGGACCGC 18

4242 23124

CFTR- IntronlO- + AAAACUCAUAAGGGACCGC 19

4243 23125

CFTR- IntronlO- + GAAAACUCAUAAGGGACCGC 20

4244 23126

CFTR- IntronlO- + AGAAAACUCAUAAGGGACCGC 21

4245 23127

CFTR- IntronlO- + GAGAAAACUCAUAAGGGACCGC 22

4246 23128

CFTR- IntronlO- + AGAGAAAACUCAUAAGGGACCGC 23

4247 23129

CFTR- IntronlO- + UAGAGAAAACUCAUAAGGGACCGC 24

4248 23130

CFTR- IntronlO- + UCUCACAGUUCUGGAGGC 18

4249 23131

CFTR- IntronlO- + UUCUCACAGUUCUGGAGGC 19

4250 23132

CFTR- IntronlO- + UUUCUCACAGUUCUGGAGGC 20

1229 20114

CFTR- IntronlO- + AUUUCUCACAGUUCUGGAGGC 21

4251 23133

CFTR- IntronlO- + UAUUUCUCACAGUUCUGGAGGC 22

4252 23134

CFTR- IntronlO- + UUAUUUCUCACAGUUCUGGAGGC 23

4253 23135

CFTR-

+ UUUAUUUCUCACAGUUCUGGAGGC 24

IntronlO- 23136

886

5535.1 4254

CFTR- IntronlO- + UACUUGGGAGGCUGAGGC 18

4255 23137

CFTR- IntronlO- + CUACUUGGGAGGCUGAGGC 19

4256 23138

CFTR-

+ GCUACUUGGGAGGCUGAGGC 20

lntronlO-681 19567

CFTR- IntronlO- + AGCUACUUGGGAGGCUGAGGC 21

4257 23139

CFTR- IntronlO- + CAGCUACUUGGGAGGCUGAGGC 22

4258 23140

CFTR- IntronlO- + CCAGCUACUUGGGAGGCUGAGGC 23

4259 23141

CFTR- IntronlO- + CCCAGCUACUUGGGAGGCUGAGGC 24

4260 23142

CFTR- IntronlO- + UACUUGGGAGGGUGAGGC 18

4261 23143

CFTR- IntronlO- + CUACUUGGGAGGGUGAGGC 19

4262 23144

CFTR-

+ GCUACUUGGGAGGGUGAGGC 20

lntronlO-682 19568

CFTR- IntronlO- + AGCUACUUGGGAGGGUGAGGC 21

4263 23145

CFTR- IntronlO- + CAGCUACUUGGGAGGGUGAGGC 22

4264 23146

CFTR- IntronlO- + CCAGCUACUUGGGAGGGUGAGGC 23

4265 23147

CFTR- IntronlO- + CCCAGCUACUUGGGAGGGUGAGGC 24

4266 23148

887

5535.1 CFTR- IntronlO- + CUGAGGCAGGAGAAUGGC 18

4267 23149

CFTR- IntronlO- + GCUGAGGCAGGAGAAUGGC 19

4268 23150

CFTR- IntronlO- + GGCUGAGGCAGGAGAAUGGC 20

4269 23151

CFTR- IntronlO- + AGGCUGAGGCAGGAGAAUGGC 21

4270 23152

CFTR- IntronlO- + GAGGCUGAGGCAGGAGAAUGGC 22

4271 23153

CFTR- IntronlO- + GGAGGCUGAGGCAGGAGAAUGGC 23

4272 23154

CFTR- IntronlO- + GGGAGGCUGAGGCAGGAGAAUGGC 24

4273 23155

CFTR- IntronlO- + UUUCAACAUAUGAAUGGC 18

4274 23156

CFTR- IntronlO- + AUUUCAACAUAUGAAUGGC 19

4275 23157

CFTR-

+ GAUUUCAACAUAUGAAUGGC 20

lntronlO-683 19569

CFTR- IntronlO- + GGAUUUCAACAUAUGAAUGGC 21

4276 23158

CFTR- IntronlO- + AGGAUUUCAACAUAUGAAUGGC 22

4277 23159

CFTR- IntronlO- + UAGGAUUUCAACAUAUGAAUGGC 23

4278 23160

CFTR- IntronlO- + UUAGGAUUUCAACAUAUGAAUGGC 24

4279 23161

CFTR-

+ AAUGGCUAUCCACAAUGC 18

IntronlO- 23162

888

5535.1 4280

CFTR- IntronlO- + AAAUGGCUAUCCACAAUGC 19

4281 23163

CFTR- IntronlO- + UAAAUGGCUAUCCACAAUGC 20

4282 23164

CFTR- IntronlO- + UUAAAUGGCUAUCCACAAUGC 21

4283 23165

CFTR- IntronlO- + UUUAAAUGGCUAUCCACAAUGC 22

4284 23166

CFTR- IntronlO- + UUUUAAAUGGCUAUCCACAAUGC 23

4285 23167

CFTR- IntronlO- + GUUUUAAAUGGCUAUCCACAAUGC 24

4286 23168

CFTR- IntronlO- + GGUUGGAUGAGGGAAUGC 18

4287 23169

CFTR- IntronlO- + UGGUUGGAUGAGGGAAUGC 19

4288 23170

CFTR-

+ UUGGUUGGAUGAGGGAAUGC 20

lntronlO-431 19317

CFTR- IntronlO- + CUUGGUUGGAUGAGGGAAUGC 21

4289 23171

CFTR- IntronlO- + CCUUGGUUGGAUGAGGGAAUGC 22

4290 23172

CFTR- IntronlO- + ACCUUGGUUGGAUGAGGGAAUGC 23

4291 23173

CFTR- IntronlO- + UACCUUGGUUGGAUGAGGGAAUGC 24

4292 23174

CFTR- IntronlO- + ACAUGAUGAAAAAUAUGC 18

4293 23175

889

5535.1 CFTR- IntronlO- + AACAUGAUGAAAAAUAUGC 19

4294 23176

CFTR- IntronlO- + AAACAUGAUGAAAAAUAUGC 20

4295 23177

CFTR- IntronlO- + UAAACAUGAUGAAAAAUAUGC 21

4296 23178

CFTR- IntronlO- + CUAAACAUGAUGAAAAAUAUGC 22

4297 23179

CFTR- IntronlO- + ACUAAACAUGAUGAAAAAUAUGC 23

4298 23180

CFTR- IntronlO- + CACUAAACAUGAUGAAAAAUAUGC 24

4299 23181

CFTR- IntronlO- + CAAUUUUAAUAAAACUGC 18

4300 23182

CFTR- IntronlO- + UCAAUUUUAAUAAAACUGC 19

4301 23183

CFTR- IntronlO- + AUCAAUUUUAAUAAAACUGC 20

4302 23184

CFTR- IntronlO- + CAUCAAUUUUAAUAAAACUGC 21

4303 23185

CFTR- IntronlO- + UCAUCAAUUUUAAUAAAACUGC 22

4304 23186

CFTR- IntronlO- + CUCAUCAAUUUUAAUAAAACUGC 23

4305 23187

CFTR- IntronlO- + GCUCAUCAAUUUUAAUAAAACUGC 24

4306 23188

CFTR- IntronlO- + GUGAGGCAGGAGAAUUGC 18

4307 23189

890

5535.1 CFTR- IntronlO- + GGUGAGGCAGGAGAAUUGC 19

4308 23190

CFTR- IntronlO- + GGGUGAGGCAGGAGAAUUGC 20

4309 23191

CFTR- IntronlO- + AGGGUGAGGCAGGAGAAUUGC 21

4310 23192

CFTR- IntronlO- + GAGGGUGAGGCAGGAGAAUUGC 22

4311 23193

CFTR- IntronlO- + GGAGGGUGAGGCAGGAGAAUUGC 23

4312 23194

CFTR- IntronlO- + GGGAGGGUGAGGCAGGAGAAUUGC 24

4313 23195

CFTR- IntronlO- + GCCACCAUCAUCACUUGC 18

4314 23196

CFTR- IntronlO- + AGCCACCAUCAUCACUUGC 19

4315 23197

CFTR- IntronlO- + AAGCCACCAUCAUCACUUGC 20

4316 23198

CFTR- IntronlO- + CAAGCCACCAUCAUCACUUGC 21

4317 23199

CFTR- IntronlO- + UCAAGCCACCAUCAUCACUUGC 22

4318 23200

CFTR- IntronlO- + AUCAAGCCACCAUCAUCACUUGC 23

4319 23201

CFTR- IntronlO- + GAUCAAGCCACCAUCAUCACUUGC 24

4320 23202

CFTR- IntronlO- + A C A A AG U A AC AG A A A A U C 18

4321 23203

891

5535.1 CFTR- IntronlO- + AACAAAG U AACAG AAAAU C 19

4322 23204

CFTR- IntronlO- + U AACAAAG U AACAG AAAAU C 20

4323 23205

CFTR- IntronlO- + GU AACAAAG U AACAG AAAAU C 21

4324 23206

CFTR- IntronlO- + AG U AACAAAG U AACAG AAAAU C 22

4325 23207

CFTR- IntronlO- + AAG U AACAAAG U AACAG AAAAU C 23

4326 23208

CFTR- IntronlO- + AAAG U AACAAAG U AACAG AAAAU C 24

4327 23209

CFTR- IntronlO- + UGCUAUUUAAACAGAAUC 18

4328 23210

CFTR- IntronlO- + GUGCUAUUUAAACAGAAUC 19

4329 23211

CFTR-

+ AGUGCUAUUUAAACAGAAUC 20

lntronlO-433 19319

CFTR- IntronlO- + CAGUGCUAUUUAAACAGAAUC 21

4330 23212

CFTR- IntronlO- + CCAGUGCUAUUUAAACAGAAUC 22

4331 23213

CFTR- IntronlO- + UCCAGUGCUAUUUAAACAGAAUC 23

4332 23214

CFTR- IntronlO- + CUCCAGUGCUAUUUAAACAGAAUC 24

4333 23215

CFTR- IntronlO- + UUUAGUAGAAACCUAAUC 18

4334 23216

CFTR-

+ UUUUAGUAGAAACCUAAUC 19

IntronlO- 23217

892

5535.1 4335

CFTR-

+ G U U U U AG U AG AAACCU AAU C 20

Intronl0-91 18977

CFTR- IntronlO- + GG U U U U AG U AG AAACCU AAU C 21

4336 23218

CFTR- IntronlO- + UGGUUUUAGUAGAAACCUAAUC 22

4337 23219

CFTR- IntronlO- + UUGGUUUUAGUAGAAACCUAAUC 23

4338 23220

CFTR- IntronlO- + UUUGGUUUUAGUAGAAACCUAAUC 24

4339 23221

CFTR- IntronlO- + GGCCGAGGCAGGCAGAUC 18

4340 23222

CFTR- IntronlO- + AGGCCGAGGCAGGCAGAUC 19

4341 23223

CFTR- IntronlO- + GAGGCCGAGGCAGGCAGAUC 20

4342 23224

CFTR- IntronlO- + GGAGGCCGAGGCAGGCAGAUC 21

4343 23225

CFTR- IntronlO- + GGGAGGCCGAGGCAGGCAGAUC 22

4344 23226

CFTR- IntronlO- + UGGGAGGCCGAGGCAGGCAGAUC 23

4345 23227

CFTR- IntronlO- + UUGGGAGGCCGAGGCAGGCAGAUC 24

4346 23228

CFTR- IntronlO- + GGCCGAGGCGGGCGGAUC 18

4347 23229

CFTR- IntronlO- + AGGCCGAGGCGGGCGGAUC 19

4348 23230

893

5535.1 CFTR- IntronlO- + GAGGCCGAGGCGGGCGGAUC 20

4349 23231

CFTR- IntronlO- + GGAGGCCGAGGCGGGCGGAUC 21

4350 23232

CFTR- IntronlO- + GGGAGGCCGAGGCGGGCGGAUC 22

4351 23233

CFTR- IntronlO- + UGGGAGGCCGAGGCGGGCGGAUC 23

4352 23234

CFTR- IntronlO- + UUGGGAGGCCGAGGCGGGCGGAUC 24

4353 23235

CFTR- IntronlO- + UCUAUCAUAGAAUUGAUC 18

4354 23236

CFTR- IntronlO- + AUCUAUCAUAGAAUUGAUC 19

4355 23237

CFTR- IntronlO- + CAUCUAUCAUAGAAUUGAUC 20

4356 23238

CFTR- IntronlO- + ACAUCUAUCAUAGAAUUGAUC 21

4357 23239

CFTR- IntronlO- + CACAUCUAUCAUAGAAUUGAUC 22

4358 23240

CFTR- IntronlO- + GCACAUCUAUCAUAGAAUUGAUC 23

4359 23241

CFTR- IntronlO- + UGCACAUCUAUCAUAGAAUUGAUC 24

4360 23242

CFTR- IntronlO- + AUACUGGGUUCAUUUAUC 18

4361 23243

CFTR- IntronlO- + UAUACUGGGUUCAUUUAUC 19

4362 23244

894

5535.1 CFTR- IntronlO- + UUAUACUGGGUUCAUUUAUC 20

4363 23245

CFTR- IntronlO- + UUUAUACUGGGUUCAUUUAUC 21

4364 23246

CFTR- IntronlO- + CUUUAUACUGGGUUCAUUUAUC 22

4365 23247

CFTR- IntronlO- + UCUUUAUACUGGGUUCAUUUAUC 23

4366 23248

CFTR- IntronlO- + GUCUUUAUACUGGGUUCAUUUAUC 24

4367 23249

CFTR- IntronlO- + CACGCUGGUCUCAAACUC 18

4368 23250

CFTR- IntronlO- + CCACGCUGGUCUCAAACUC 19

4369 23251

CFTR- IntronlO- + CCCACGCUGGUCUCAAACUC 20

4370 23252

CFTR- IntronlO- + GCCCACGCUGGUCUCAAACUC 21

4371 23253

CFTR- IntronlO- + UGCCCACGCUGGUCUCAAACUC 22

4372 23254

CFTR- IntronlO- + UUGCCCACGCUGGUCUCAAACUC 23

4373 23255

CFTR- IntronlO- + GUUGCCCACGCUGGUCUCAAACUC 24

4374 23256

CFTR- IntronlO- + GUAUUAGCAAGUGGACUC 18

4375 23257

CFTR- IntronlO- + UGUAUUAGCAAGUGGACUC 19

4376 23258

895

5535.1 CFTR- IntronlO- + UUGUAUUAGCAAGUGGACUC 20

4377 23259

CFTR- IntronlO- + AUUGUAUUAGCAAGUGGACUC 21

4378 23260

CFTR- IntronlO- + AAUUGUAUUAGCAAGUGGACUC 22

4379 23261

CFTR- IntronlO- + CAAUUGUAUUAGCAAGUGGACUC 23

4380 23262

CFTR- IntronlO- + UCAAUUGUAUUAGCAAGUGGACUC 24

4381 23263

CFTR- IntronlO- + ACUAAAGACUUCACCCUC 18

4382 23264

CFTR- IntronlO- + UACUAAAGACUUCACCCUC 19

4383 23265

CFTR- IntronlO- + UUACUAAAGACUUCACCCUC 20

4384 23266

CFTR- IntronlO- + UUUACUAAAGACUUCACCCUC 21

4385 23267

CFTR- IntronlO- + AUUUACUAAAGACUUCACCCUC 22

4386 23268

CFTR- IntronlO- + CAUUUACUAAAGACUUCACCCUC 23

4387 23269

CFTR- IntronlO- + UCAUUUACUAAAGACUUCACCCUC 24

4388 23270

CFTR- IntronlO- + CCACCCAAUUUUUGGCUC 18

4389 23271

CFTR- IntronlO- + CCCACCCAAUUUUUGGCUC 19

4390 23272

896

5535.1 CFTR- IntronlO- + CCCCACCCAAUUUUUGGCUC 20

4391 23273

CFTR- IntronlO- + CCCCCACCCAAUUUUUGGCUC 21

4392 23274

CFTR- IntronlO- + UCCCCCACCCAAUUUUUGGCUC 22

4393 23275

CFTR- IntronlO- + CUCCCCCACCCAAUUUUUGGCUC 23

4394 23276

CFTR- IntronlO- + GCUCCCCCACCCAAUUUUUGGCUC 24

4395 23277

CFTR- IntronlO- + UAUAGAGAGAAACAUCUC 18

4396 23278

CFTR- IntronlO- + AUAUAGAGAGAAACAUCUC 19

4397 23279

CFTR- IntronlO- + UAUAUAGAGAGAAACAUCUC 20

1238 20123

CFTR- IntronlO- + AUAUAUAGAGAGAAACAUCUC 21

4398 23280

CFTR- IntronlO- + UAUAUAUAGAGAGAAACAUCUC 22

4399 23281

CFTR- IntronlO- + AUAUAUAUAGAGAGAAACAUCUC 23

4400 23282

CFTR- IntronlO- + UAUAUAUAUAGAGAGAAACAUCUC 24

4401 23283

CFTR- IntronlO- + UUUAAUUGCCAGUAAGUC 18

4402 23284

CFTR- IntronlO- + AUUUAAUUGCCAGUAAGUC 19

4403 23285

897

5535.1 CFTR- IntronlO- + AAUUUAAUUGCCAGUAAGUC 20

4404 23286

CFTR- IntronlO- + AAAUUUAAUUGCCAGUAAGUC 21

4405 23287

CFTR- IntronlO- + GAAAUUUAAUUGCCAGUAAGUC 22

4406 23288

CFTR- IntronlO- + UGAAAUUUAAUUGCCAGUAAGUC 23

4407 23289

CFTR- IntronlO- + CUGAAAUUUAAUUGCCAGUAAGUC 24

4408 23290

CFTR- IntronlO- + CCUUCCAGUUACUCAGUC 18

4409 23291

CFTR- IntronlO- + UCCUUCCAGUUACUCAGUC 19

4410 23292

CFTR- IntronlO- + AUCCUUCCAGUUACUCAGUC 20

4411 23293

CFTR- IntronlO- + UAUCCUUCCAGUUACUCAGUC 21

4412 23294

CFTR- IntronlO- + UUAUCCUUCCAGUUACUCAGUC 22

4413 23295

CFTR- IntronlO- + UUUAUCCUUCCAGUUACUCAGUC 23

4414 23296

CFTR- IntronlO- + AUUUAUCCUUCCAGUUACUCAGUC 24

4415 23297

CFTR- IntronlO- + AUAAGCCAGCUUUCAGUC 18

4416 23298

CFTR- IntronlO- + CAUAAGCCAGCUUUCAGUC 19

4417 23299

898

5535.1 CFTR- IntronlO- + CCAUAAGCCAGCUUUCAGUC 20

4418 23300

CFTR- IntronlO- + GCCAUAAGCCAGCUUUCAGUC 21

4419 23301

CFTR- IntronlO- + UGCCAUAAGCCAGCUUUCAGUC 22

4420 23302

CFTR- IntronlO- + AUGCCAUAAGCCAGCUUUCAGUC 23

4421 23303

CFTR- IntronlO- + GAUGCCAUAAGCCAGCUUUCAGUC 24

4422 23304

CFTR- IntronlO- + CGGGCGGAUCACGAGGUC 18

4423 23305

CFTR- IntronlO- + GCGGGCGGAUCACGAGGUC 19

4424 23306

CFTR-

+ GGCGGGCGGAUCACGAGGUC 20

lntronlO-688 19574

CFTR- IntronlO- + AGGCGGGCGGAUCACGAGGUC 21

4425 23307

CFTR- IntronlO- + GAGGCGGGCGGAUCACGAGGUC 22

4426 23308

CFTR- IntronlO- + CGAGGCGGGCGGAUCACGAGGUC 23

4427 23309

CFTR- IntronlO- + CCGAGGCGGGCGGAUCACGAGGUC 24

4428 23310

CFTR- IntronlO- + CAGGCAGAUCAUGAGGUC 18

4429 23311

CFTR- IntronlO- + GCAGGCAGAUCAUGAGGUC 19

4430 23312

CFTR-

+ GGCAGGCAGAUCAUGAGGUC 20

IntronlO- 23313

899

5535.1 4431

CFTR- IntronlO- + AGGCAGGCAGAUCAUGAGGUC 21

4432 23314

CFTR- IntronlO- + GAGGCAGGCAGAUCAUGAGGUC 22

4433 23315

CFTR- IntronlO- + CGAGGCAGGCAGAUCAUGAGGUC 23

4434 23316

CFTR- IntronlO- + CCGAGGCAGGCAGAUCAUGAGGUC 24

4435 23317

CFTR- IntronlO- + GCUUCACUAAAAUAAUUC 18

4436 23318

CFTR- IntronlO- + UGCUUCACUAAAAUAAUUC 19

4437 23319

CFTR- IntronlO- + UUGCUUCACUAAAAUAAUUC 20

4438 23320

CFTR- IntronlO- + AUUGCUUCACUAAAAUAAUUC 21

4439 23321

CFTR- IntronlO- + UAUUGCUUCACUAAAAUAAUUC 22

4440 23322

CFTR- IntronlO- + AUAUUGCUUCACUAAAAUAAUUC 23

4441 23323

CFTR- IntronlO- + AAUAUUGCUUCACUAAAAUAAUUC 24

4442 23324

CFTR- IntronlO- + GAUUAUUCGGUAUAAUUC 18

4443 23325

CFTR- IntronlO- + AGAUUAUUCGGUAUAAUUC 19

4444 23326

CFTR-

+ UAGAUUAUUCGGUAUAAUUC 20

IntronlO- 23327

900

5535.1 4445

CFTR- IntronlO- + UUAGAUUAUUCGGUAUAAUUC 21

4446 23328

CFTR- IntronlO- + CUUAGAUUAUUCGGUAUAAUUC 22

4447 23329

CFTR- IntronlO- + UCUUAGAUUAUUCGGUAUAAUUC 23

4448 23330

CFTR- IntronlO- + GUCUUAGAUUAUUCGGUAUAAUUC 24

4449 23331

CFTR- IntronlO- + AAAUCUAAAAGCUAAUUC 18

4450 23332

CFTR- IntronlO- + UAAAUCUAAAAGCUAAUUC 19

4451 23333

CFTR- IntronlO- + GUAAAUCUAAAAGCUAAUUC 20

4452 23334

CFTR- IntronlO- + AGUAAAUCUAAAAGCUAAUUC 21

4453 23335

CFTR- IntronlO- + A AG U AAA U C U A A A AG C U A A U U C 22

4454 23336

CFTR- IntronlO- + UAAGUAAAUCUAAAAGCUAAUUC 23

4455 23337

CFTR- IntronlO- + AUAAGUAAAUCUAAAAGCUAAUUC 24

4456 23338

CFTR- IntronlO- + AUAAUUUGAACAACAUUC 18

4457 23339

CFTR- IntronlO- + AAUAAU U UG AACAACAU U C 19

4458 23340

CFTR-

+ AAAUAAU U UG AACAACAU U C 20

IntronlO- 23341

901

5535.1 4459

CFTR- IntronlO- + G AAAU AAU U UG AACAACAU U C 21

4460 23342

CFTR- IntronlO- + AG AAAU AAU U UG AACAACAU U C 22

4461 23343

CFTR- IntronlO- + U AG AAAU AAU U UG AACAACAU U C 23

4462 23344

CFTR- IntronlO- + G U AG AAAU AAU U UG AACAACAU U C 24

4463 23345

CFTR- IntronlO- + AUUUAAAAAGCAAUAUUC 18

4464 23346

CFTR- IntronlO- + AAU U U AAAAAG CAAU AUUC 19

4465 23347

CFTR- IntronlO- + AAAU U U AAAAAG C A A U A U U C 20

4466 23348

CFTR- IntronlO- + U AAA U U U AAAAAG C A A U A U U C 21

4467 23349

CFTR- IntronlO- + U U AAAU U U AAAAAG C A A U A U U C 22

4468 23350

CFTR- IntronlO- + AU U AAAU U U AAAAAG CAAU AU U C 23

4469 23351

CFTR- IntronlO- + U AU U AAAU U U AAAAAG CAAU AU U C 24

4470 23352

CFTR- IntronlO- + ACACAAUGGGUUAUAUUC 18

4471 23353

CFTR- IntronlO- + UACACAAUGGGUUAUAUUC 19

4472 23354

CFTR-

+ CUACACAAUGGGUUAUAUUC 20

IntronlO- 23355

902

5535.1 4473

CFTR- IntronlO- + UCUACACAAUGGGUUAUAUUC 21

4474 23356

CFTR- IntronlO- + AUCUACACAAUGGGUUAUAUUC 22

4475 23357

CFTR- IntronlO- + UAUCUACACAAUGGGUUAUAUUC 23

4476 23358

CFTR- IntronlO- + UUAUCUACACAAUGGGUUAUAUUC 24

4477 23359

CFTR- IntronlO- + AGUAUUUUGAAAAGCUUC 18

4478 23360

CFTR- IntronlO- + AAGUAUUUUGAAAAGCUUC 19

4479 23361

CFTR- IntronlO- + AAAGUAUUUUGAAAAGCUUC 20

4480 23362

CFTR- IntronlO- + GAAAGUAUUUUGAAAAGCUUC 21

4481 23363

CFTR- IntronlO- + AGAAAGUAUUUUGAAAAGCUUC 22

4482 23364

CFTR- IntronlO- + UAGAAAGUAUUUUGAAAAGCUUC 23

4483 23365

CFTR- IntronlO- + CUAGAAAGUAUUUUGAAAAGCUUC 24

4484 23366

CFTR- IntronlO- + AUUUAUUUCUCACAGUUC 18

4485 23367

CFTR- IntronlO- + AAUUUAUUUCUCACAGUUC 19

4486 23368

CFTR-

+ GAAUUUAUUUCUCACAGUUC 20

lntronlO-689 19575

903

5535.1 CFTR- IntronlO- + GGAAUUUAUUUCUCACAGUUC 21

4487 23369

CFTR- IntronlO- + AGGAAUUUAUUUCUCACAGUUC 22

4488 23370

CFTR- IntronlO- + CAGGAAUUUAUUUCU CACAG U U C 23

4489 23371

CFTR- IntronlO- + ACAGGAAUUUAUUUCUCACAGUUC 24

4490 23372

CFTR- IntronlO- + CGAAUUGGUACAAAUUUC 18

4491 23373

CFTR- IntronlO- + ACG AAU UGG U ACAAAU U U C 19

4492 23374

CFTR-

+ UACGAAUUGGUACAAAUUUC 20

Intron 10-443 19329

CFTR- IntronlO- + GUACGAAUUGGUACAAAUUUC 21

4493 23375

CFTR- IntronlO- + AG U ACG AAU UGG U ACAAAU U U C 22

4494 23376

CFTR- IntronlO- + GAG U ACG AAU UGG U ACAAAU U U C 23

4495 23377

CFTR- IntronlO- + UGAGUACGAAUUGGUACAAAUUUC 24

4496 23378

CFTR- IntronlO- + GAAAAUUUGUUUUCUUUC 18

4497 23379

CFTR- IntronlO- + AGAAAAUUUGUUUUCUUUC 19

4498 23380

CFTR- IntronlO- + AAGAAAAUUUGUUUUCUUUC 20

1248 20133

CFTR-

+ AAAGAAAAUUUGUUUUCUUUC 21

IntronlO- 23381

904

5535.1 4499

CFTR- IntronlO- + CAAAGAAAAUUUGUUUUCUUUC 22

4500 23382

CFTR- IntronlO- + ACAAAGAAAAUUUGUUUUCUUUC 23

4501 23383

CFTR- IntronlO- + AACAAAGAAAAUUUGUUUUCUUUC 24

4502 23384

CFTR- IntronlO- + U CAAAG CU ACAG AU U U U C 18

4503 23385

CFTR- IntronlO- + AUCAAAGCUACAGAUUUUC 19

4504 23386

CFTR- IntronlO- + AAUCAAAGCUACAGAUUUUC 20

4505 23387

CFTR- IntronlO- + AAAUCAAAGCUACAGAUUUUC 21

4506 23388

CFTR- IntronlO- + UAAAUCAAAGCUACAGAUUUUC 22

4507 23389

CFTR- IntronlO- + AUAAAUCAAAGCUACAGAUUUUC 23

4508 23390

CFTR- IntronlO- + UAUAAAUCAAAGCUACAGAUUUUC 24

4509 23391

CFTR- IntronlO- + UUGCUUUAU UAAGAAAAG 18

4510 23392

CFTR- IntronlO- + AUUGCUUUAUUAAGAAAAG 19

4511 23393

CFTR- IntronlO- + GAUUGCUUUAUUAAGAAAAG 20

4512 23394

CFTR-

+ UGAUUGCUUUAUUAAGAAAAG 21

IntronlO- 23395

905

5535.1 4513

CFTR- IntronlO- + CUGAUUGCUUUAUUAAGAAAAG 22

4514 23396

CFTR- IntronlO- + GCUGAUUGCUUUAUUAAGAAAAG 23

4515 23397

CFTR- IntronlO- + UGCUGAUUGCUUUAUUAAGAAAAG 24

4516 23398

CFTR- IntronlO- + GGAUAUCUUAGGUCAAAG 18

4517 23399

CFTR- IntronlO- + AGGAUAUCUUAGGUCAAAG 19

4518 23400

CFTR-

+ UAGGAUAUCUUAGGUCAAAG 20

Intron 10-447 19333

CFTR- IntronlO- + UUAGGAUAUCUUAGGUCAAAG 21

4519 23401

CFTR- IntronlO- + CUU AGGAUAUCUUAGGUCAAAG 22

4520 23402

CFTR- IntronlO- + CCUUAGGAUAUCUUAGGUCAAAG 23

4521 23403

CFTR- IntronlO- + CCCUUAGGAUAUCUUAGGUCAAAG 24

4522 23404

CFTR- IntronlO- + UGUUAAUGG C A A AG C A AG 18

4523 23405

CFTR- IntronlO- + CUGUUAAUGGCAAAGCAAG 19

4524 23406

CFTR- IntronlO- + UCUGUUAAUGGCAAAGCAAG 20

4525 23407

CFTR- IntronlO- + AUCUGUUAAUGGCAAAGCAAG 21

4526 23408

906

5535.1 CFTR- IntronlO- + UAUCUGUUAAUGGCAAAGCAAG 22

4527 23409

CFTR- IntronlO- + UUAUCUGUUAAUGGCAAAGCAAG 23

4528 23410

CFTR- IntronlO- + UUUAUCUGUUAAUGGCAAAGCAAG 24

4529 23411

CFTR- IntronlO- + UUGGGUAAGUUAUAGAAG 18

4530 23412

CFTR- IntronlO- + UUUGGGUAAGUUAUAGAAG 19

4531 23413

CFTR- IntronlO- + AUUUGGGUAAGUUAUAGAAG 20

4532 23414

CFTR- IntronlO- + UAUUUGGGUAAGUUAUAGAAG 21

4533 23415

CFTR- IntronlO- + AUAUUUGGGUAAGUUAUAGAAG 22

4534 23416

CFTR- IntronlO- + CAUAUUUGGGUAAGUUAUAGAAG 23

4535 23417

CFTR- IntronlO- + ACAUAUUUGGGUAAGUUAUAGAAG 24

4536 23418

CFTR- IntronlO- + CACUUUGGGAGGCUGAAG 18

4537 23419

CFTR- IntronlO- + GCACUUUGGGAGGCUGAAG 19

4538 23420

CFTR- IntronlO- + AGCACUUUGGGAGGCUGAAG 20

1252 20137

CFTR- IntronlO- + CAGCACUUUGGGAGGCUGAAG 21

4539 23421

907

5535.1 CFTR- IntronlO- + CCAGCACUUUGGGAGGCUGAAG 22

4540 23422

CFTR- IntronlO- + CCCAGCACUUUGGGAGGCUGAAG 23

4541 23423

CFTR- IntronlO- + ACCCAGCACUUUGGGAGGCUGAAG 24

4542 23424

CFTR- IntronlO- + UACUAUUUUCCCUAUAAG 18

4543 23425

CFTR- IntronlO- + AUACUAUUUUCCCUAUAAG 19

4544 23426

CFTR- IntronlO- + CAUACUAUUUUCCCUAUAAG 20

4545 23427

CFTR- IntronlO- + ACAUACUAUUUUCCCUAUAAG 21

4546 23428

CFTR- IntronlO- + GACAUACUAUUUUCCCUAUAAG 22

4547 23429

CFTR- IntronlO- + UGACAUACUAUUUUCCCUAUAAG 23

4548 23430

CFTR- IntronlO- + UUGACAUACUAUUUUCCCUAUAAG 24

4549 23431

CFTR- IntronlO- + AUUCCUCCUGUGUAUAAG 18

4550 23432

CFTR- IntronlO- + AAUUCCUCCUGUGUAUAAG 19

4551 23433

CFTR- IntronlO- + AAAUUCCUCCUGUGUAUAAG 20

4552 23434

CFTR- IntronlO- + GAAAUUCCUCCUGUGUAUAAG 21

4553 23435

908

5535.1 CFTR- IntronlO- + AGAAAUUCCUCCUGUGUAUAAG 22

4554 23436

CFTR- IntronlO- + GAGAAAUUCCUCCUGUGUAUAAG 23

4555 23437

CFTR- IntronlO- + AGAGAAAUUCCUCCUGUGUAUAAG 24

4556 23438

CFTR- IntronlO- + CUUAACCCAUCUAUUAAG 18

4557 23439

CFTR- IntronlO- + GCUUAACCCAUCUAUUAAG 19

4558 23440

CFTR-

+ GGCUUAACCCAUCUAUUAAG 20

lntronlO-97 18983

CFTR- IntronlO- + UGGCUUAACCCAUCUAUUAAG 21

4559 23441

CFTR- IntronlO- + UUGGCUUAACCCAUCUAUUAAG 22

4560 23442

CFTR- IntronlO- + GUUGGCUUAACCCAUCUAUUAAG 23

4561 23443

CFTR- IntronlO- + AGUUGGCUUAACCCAUCUAUUAAG 24

4562 23444

CFTR- IntronlO- + CUGUGAUGCAGACAACAG 18

4563 23445

CFTR- IntronlO- + GCUGUGAUGCAGACAACAG 19

4564 23446

CFTR- IntronlO- + AGCUGUGAUGCAGACAACAG 20

4565 23447

CFTR- IntronlO- + CAGCUGUGAUGCAGACAACAG 21

4566 23448

CFTR-

+ UCAGCUGUGAUGCAGACAACAG 22

IntronlO- 23449

909

5535.1 4567

CFTR- IntronlO- + UUCAGCUGUGAUGCAGACAACAG 23

4568 23450

CFTR- IntronlO- + C U U CAG CUGUGAUG CAG AC AACAG 24

4569 23451

CFTR- IntronlO- + AGAAUGGAAAAUGGACAG 18

4570 23452

CFTR- IntronlO- + GAGAAUGGAAAAUGGACAG 19

4571 23453

CFTR- IntronlO- + GGAGAAUGGAAAAUGGACAG 20

4572 23454

CFTR- IntronlO- + AGGAGAAUGGAAAAUGGACAG 21

4573 23455

CFTR- IntronlO- + CAGGAGAAUGGAAAAUGGACAG 22

4574 23456

CFTR- IntronlO- + GCAGGAGAAUGGAAAAUGGACAG 23

4575 23457

CFTR- IntronlO- + UGCAGGAGAAUGGAAAAUGGACAG 24

4576 23458

CFTR- IntronlO- + AGCUAAAGUAUUACCCAG 18

4577 23459

CFTR- IntronlO- + CAGCUAAAGUAUUACCCAG 19

4578 23460

CFTR-

+ ACAGCUAAAG U AU U ACCCAG 20

lntronlO-451 19337

CFTR- IntronlO- + UACAGCUAAAG U AU U ACCCAG 21

4579 23461

CFTR- IntronlO- + AUACAGCUAAAGUAUUACCCAG 22

4580 23462

910

5535.1 CFTR- IntronlO- + UAUACAGCUAAAGUAUUACCCAG 23

4581 23463

CFTR- IntronlO- + AUAUACAGCUAAAGUAUUACCCAG 24

4582 23464

CFTR- IntronlO- + GAUAAAAAUUCCAAGCAG 18

4583 23465

CFTR- IntronlO- + U G A U A A A A A U U C C A AG C AG 19

4584 23466

CFTR- IntronlO- + A U G A U A A A A A U U C C A AG C AG 20

4585 23467

CFTR- IntronlO- + A A U G A U A A A A A UUCCAAGCAG 21

4586 23468

CFTR- IntronlO- + A A A U G A U A A A A A U U C C A AG C AG 22

4587 23469

CFTR- IntronlO- + AAAAUGAUAAAAAUUCCAAGCAG 23

4588 23470

CFTR- IntronlO- + AAAAAUGAUAAAAAUUCCAAGCAG 24

4589 23471

CFTR- IntronlO- + AAG G AAAG G AG G U AG CAG 18

4590 23472

CFTR- IntronlO- + GAAGGAAAGGAGGUAGCAG 19

4591 23473

CFTR- IntronlO- + AGAAGGAAAGGAGGUAGCAG 20

1260 20145

CFTR- IntronlO- + UAGAAGGAAAGGAGGUAGCAG 21

4592 23474

CFTR- IntronlO- + G U AG AAG G AAAG GAG G U AG CAG 22

4593 23475

911

5535.1 CFTR- IntronlO- + AGUAGAAGGAAAGGAGGUAGCAG 23

4594 23476

CFTR- IntronlO- + GAGUAGAAGGAAAGGAGGUAGCAG 24

4595 23477

CFTR- IntronlO- + UCAACAUAUGAAUGGCAG 18

4596 23478

CFTR- IntronlO- + UUCAACAUAUGAAUGGCAG 19

4597 23479

CFTR- IntronlO- + UUUCAACAUAUGAAUGGCAG 20

1263 20148

CFTR- IntronlO- + AUUUCAACAUAUGAAUGGCAG 21

4598 23480

CFTR- IntronlO- + GAUUUCAACAUAUGAAUGGCAG 22

4599 23481

CFTR- IntronlO- + GGAUUUCAACAUAUGAAUGGCAG 23

4600 23482

CFTR- IntronlO- + AGGAUUUCAACAUAUGAAUGGCAG 24

4601 23483

CFTR- IntronlO- + CU AU U U AAACAG AAU CAG 18

4602 23484

CFTR- IntronlO- + GCUAUUUAAACAGAAUCAG 19

4603 23485

CFTR-

+ UG CU AU U U AAACAG AAU CAG 20

lntronlO-453 19339

CFTR- IntronlO- + GUGCUAUUUAAACAGAAUCAG 21

4604 23486

CFTR- IntronlO- + AGUGCUAUUUAAACAGAAUCAG 22

4605 23487

CFTR-

+ CAGUGCUAUUUAAACAGAAUCAG 23

IntronlO- 23488

912

5535.1 4606

CFTR- IntronlO- + CCAGUGCUAUUUAAACAGAAUCAG 24

4607 23489

CFTR- IntronlO- + CAUAAUAAGACAGCUCAG 18

4608 23490

CFTR- IntronlO- + ACAUAAUAAGACAGCUCAG 19

4609 23491

CFTR- IntronlO- + AACAUAAUAAGACAGCUCAG 20

4610 23492

CFTR- IntronlO- + A A AC A U A A U A AG AC AG C U C AG 21

4611 23493

CFTR- IntronlO- + AAAACAUAAUAAGACAGCUCAG 22

4612 23494

CFTR- IntronlO- + CAAAACAUAAUAAGACAGCUCAG 23

4613 23495

CFTR- IntronlO- + ACAAAACAUAAUAAGACAGCUCAG 24

4614 23496

CFTR- IntronlO- + AAGAGGAAAAGACUUCAG 18

4615 23497

CFTR- IntronlO- + UAAGAGGAAAAGACUUCAG 19

4616 23498

CFTR- IntronlO- + UUAAGAGGAAAAGACUUCAG 20

4617 23499

CFTR- IntronlO- + AU U AAG AGG AAAAG ACU U CAG 21

4618 23500

CFTR- IntronlO- + U AU U AAG AGG AAAAG ACU U CAG 22

4619 23501

CFTR-

+ CUAUUAAGAGGAAAAGACUUCAG 23

IntronlO- 23502

913

5535.1 4620

CFTR- IntronlO- + U CU AU U AAG AGG AAAAG ACU U CAG 24

4621 23503

CFTR- IntronlO- + UGUUACAUAAAAAGAGAG 18

4622 23504

CFTR- IntronlO- + UUGUUACAUAAAAAGAGAG 19

4623 23505

CFTR- IntronlO- + AU UG U U ACAU AAAAAG AG AG 20

4624 23506

CFTR- IntronlO- + U AU UG U U ACAU AAAAAG AG AG 21

4625 23507

CFTR- IntronlO- + AUAUUGUUACAUAAAAAGAGAG 22

4626 23508

CFTR- IntronlO- + CAUAUUGUUACAUAAAAAGAGAG 23

4627 23509

CFTR- IntronlO- + GCAUAUUGUUACAUAAAAAGAGAG 24

4628 23510

CFTR- IntronlO- + UUUGUAUUUUUAGUAGAG 18

4629 23511

CFTR- IntronlO- + UUUUGUAUUUUUAGUAGAG 19

4630 23512

CFTR- IntronlO- + UUUUUGUAUUUUUAGUAGAG 20

4631 23513

CFTR- IntronlO- + UUUUUUGUAUUUUUAGUAGAG 21

4632 23514

CFTR- IntronlO- + AUUUUUUGUAUUUUUAGUAGAG 22

4633 23515

CFTR-

+ AAUUUUUUGUAUUUUUAGUAGAG 23

IntronlO- 23516

914

5535.1 4634

CFTR- IntronlO- + UAAUUUUUUGUAUUUUUAGUAGAG 24

4635 23517

CFTR- IntronlO- + UUUGUGUUUUUUGUAGAG 18

4636 23518

CFTR- IntronlO- + GUUUGUGUUUUUUGUAGAG 19

4637 23519

CFTR- IntronlO- + UGUUUGUGUUUUUUGUAGAG 20

4638 23520

CFTR- IntronlO- + UUGUUUGUGUUUUUUGUAGAG 21

4639 23521

CFTR- IntronlO- + UUUGUUUGUGUUUUUUGUAGAG 22

4640 23522

CFTR- IntronlO- + UUUUGUUUGUGUUUUUUGUAGAG 23

4641 23523

CFTR- IntronlO- + CUUUUGUUUGUGUUUUUUGUAGAG 24

4642 23524

CFTR- IntronlO- + GCACUUUGGGAGGCCGAG 18

4643 23525

CFTR- IntronlO- + AGCACUUUGGGAGGCCGAG 19

4644 23526

CFTR- IntronlO- + CAGCACUUUGGGAGGCCGAG 20

4645 23527

CFTR- IntronlO- + CCAGCACUUUGGGAGGCCGAG 21

4646 23528

CFTR- IntronlO- + CCCAGCACUUUGGGAGGCCGAG 22

4647 23529

CFTR-

+ UCCCAGCACUUUGGGAGGCCGAG 23

IntronlO- 23530

915

5535.1 4648

CFTR- IntronlO- + AUCCCAGCACUUUGGGAGGCCGAG 24

4649 23531

CFTR- IntronlO- + CUAAUGGCAGAAUUCGAG 18

4650 23532

CFTR- IntronlO- + ACUAAUGGCAGAAUUCGAG 19

4651 23533

CFTR- IntronlO- + AACUAAUGGCAGAAUUCGAG 20

4652 23534

CFTR- IntronlO- + AAACUAAUGGCAGAAUUCGAG 21

4653 23535

CFTR- IntronlO- + AAAACUAAUGGCAGAAUUCGAG 22

4654 23536

CFTR- IntronlO- + UAAAACUAAUGGCAGAAUUCGAG 23

4655 23537

CFTR- IntronlO- + UUAAAACUAAUGGCAGAAUUCGAG 24

4656 23538

CFTR- IntronlO- + AUGGCGUGAACCCGGGAG 18

4657 23539

CFTR- IntronlO- + AAUGGCGUGAACCCGGGAG 19

4658 23540

CFTR- IntronlO- + GAAUGGCGUGAACCCGGGAG 20

4659 23541

CFTR- IntronlO- + AGAAUGGCGUGAACCCGGGAG 21

4660 23542

CFTR- IntronlO- + GAGAAUGGCGUGAACCCGGGAG 22

4661 23543

CFTR-

+ GGAGAAUGGCGUGAACCCGGGAG 23

IntronlO- 23544

916

5535.1 4662

CFTR- IntronlO- + AGGAGAAUGGCGUGAACCCGGGAG 24

4663 23545

CFTR- IntronlO- + UUAGGGUGGGAUAUGGAG 18

4664 23546

CFTR- IntronlO- + CUUAGGGUGGGAUAUGGAG 19

4665 23547

CFTR- IntronlO- + UCUUAGGGUGGGAUAUGGAG 20

4666 23548

CFTR- IntronlO- + UUCUUAGGGUGGGAUAUGGAG 21

4667 23549

CFTR- IntronlO- + GUUCUUAGGGUGGGAUAUGGAG 22

4668 23550

CFTR- IntronlO- + UGUUCUUAGGGUGGGAUAUGGAG 23

4669 23551

CFTR- IntronlO- + UUGUUCUUAGGGUGGGAUAUGGAG 24

4670 23552

CFTR- IntronlO- + CUACUGACUAAAACUGAG 18

4671 23553

CFTR- IntronlO- + ACUACUGACUAAAACUGAG 19

4672 23554

CFTR- IntronlO- + UACUACUGACUAAAACUGAG 20

4673 23555

CFTR- IntronlO- + AUACUACUGACUAAAACUGAG 21

4674 23556

CFTR- IntronlO- + AAUACUACUGACUAAAACUGAG 22

4675 23557

CFTR-

+ UAAUACUACUGACUAAAACUGAG 23

IntronlO- 23558

917

5535.1 4676

CFTR- IntronlO- + AUAAUACUACUGACUAAAACUGAG 24

4677 23559

CFTR- IntronlO- + GGCGGAGCUUGCAGUGAG 18

4678 23560

CFTR- IntronlO- + AGGCGGAGCUUGCAGUGAG 19

4679 23561

CFTR- IntronlO- + GAGGCGGAGCUUGCAGUGAG 20

4680 23562

CFTR- IntronlO- + GGAGGCGGAGCUUGCAGUGAG 21

4681 23563

CFTR- IntronlO- + GGGAGGCGGAGCUUGCAGUGAG 22

4682 23564

CFTR- IntronlO- + CGGGAGGCGGAGCUUGCAGUGAG 23

4683 23565

CFTR- IntronlO- + CCGGGAGGCGGAGCUUGCAGUGAG 24

4684 23566

CFTR- IntronlO- + GGCAGAGGUUGCAGUGAG 18

4685 23567

CFTR- IntronlO- + AGGCAGAGGUUGCAGUGAG 19

4686 23568

CFTR- IntronlO- + GAGGCAGAGGUUGCAGUGAG 20

4687 23569

CFTR- IntronlO- + GGAGGCAGAGGUUGCAGUGAG 21

4688 23570

CFTR- IntronlO- + GGGAGGCAGAGGUUGCAGUGAG 22

4689 23571

CFTR-

+ CGGGAGGCAGAGGUUGCAGUGAG 23

IntronlO- 23572

918

5535.1 4690

CFTR- IntronlO- + CCGGGAGGCAGAGGUUGCAGUGAG 24

4691 23573

CFTR- IntronlO- + G ACACCAAAU U U AU UG AG 18

4692 23574

CFTR- IntronlO- + U G ACACCAAAU U U AU UG AG 19

4693 23575

CFTR-

+ CUG ACACCAAAU U U AU U GAG 20

lntronlO-457 19343

CFTR- IntronlO- + CCUGACACCAAAUUUAUUGAG 21

4694 23576

CFTR- IntronlO- + GCCUGACACCAAAUUUAUUGAG 22

4695 23577

CFTR- IntronlO- + AGCCUGACACCAAAUUUAUUGAG 23

4696 23578

CFTR- IntronlO- + CAGCCUGACACCAAAUUUAUUGAG 24

4697 23579

CFTR- IntronlO- + UAAUAGCCUAUUGUUGAG 18

4698 23580

CFTR- IntronlO- + CUAAUAGCCUAUUGUUGAG 19

4699 23581

CFTR- IntronlO- + ACUAAUAGCCUAUUGUUGAG 20

1271 20156

CFTR- IntronlO- + UACUAAUAGCCUAUUGUUGAG 21

4700 23582

CFTR- IntronlO- + CUACUAAUAGCCUAUUGUUGAG 22

4701 23583

CFTR- IntronlO- + ACUACUAAUAGCCUAUUGUUGAG 23

4702 23584

919

5535.1 CFTR- IntronlO- + AACUACUAAUAGCCUAUUGUUGAG 24

4703 23585

CFTR- IntronlO- + CUAGAUGAUUAUUAAUAG 18

4704 23586

CFTR- IntronlO- + CCUAGAUGAUUAUUAAUAG 19

4705 23587

CFTR-

+ GCCUAGAUGAUUAUUAAUAG 20

lntronlO-100 18986

CFTR- IntronlO- + AGCCUAGAUGAUUAUUAAUAG 21

4706 23588

CFTR- IntronlO- + CAGCCUAGAUGAUUAUUAAUAG 22

4707 23589

CFTR- IntronlO- + GCAGCCUAGAUGAUUAUUAAUAG 23

4708 23590

CFTR- IntronlO- + UGCAGCCUAGAUGAUUAUUAAUAG 24

4709 23591

CFTR- IntronlO- + GAAAGUUGUCCAAGAUAG 18

4710 23592

CFTR- IntronlO- + GGAAAGUUGUCCAAGAUAG 19

4711 23593

CFTR-

+ UGGAAAGUUGUCCAAGAUAG 20

lntronlO-459 19345

CFTR- IntronlO- + AUGGAAAGUUGUCCAAGAUAG 21

4712 23594

CFTR- IntronlO- + UAUGGAAAGUUGUCCAAGAUAG 22

4713 23595

CFTR- IntronlO- + AUAUGGAAAGUUGUCCAAGAUAG 23

4714 23596

CFTR- IntronlO- + AAUAUGGAAAGUUGUCCAAGAUAG 24

4715 23597

920

5535.1 CFTR- IntronlO- + CCUCAGCCUCCCAAGUAG 18

4716 23598

CFTR- IntronlO- + ACCUCAGCCUCCCAAGUAG 19

4717 23599

CFTR- IntronlO- + CACCUCAGCCUCCCAAGUAG 20

4718 23600

CFTR- IntronlO- + CCACCUCAGCCUCCCAAGUAG 21

4719 23601

CFTR- IntronlO- + CCCACCUCAGCCUCCCAAGUAG 22

4720 23602

CFTR- IntronlO- + UCCCACCUCAGCCUCCCAAGUAG 23

4721 23603

CFTR- IntronlO- + CUCCCACCUCAGCCUCCCAAGUAG 24

4722 23604

CFTR- IntronlO- + GGUAAGUUAUAGAAGUAG 18

4723 23605

CFTR- IntronlO- + GGG UAAG U U AU AG AAG U AG 19

4724 23606

CFTR- IntronlO- + UGGGUAAGUUAUAGAAGUAG 20

4725 23607

CFTR- IntronlO- + UUGGGUAAGUUAUAGAAGUAG 21

4726 23608

CFTR- IntronlO- + UUUGGGUAAGUUAUAGAAGUAG 22

4727 23609

CFTR- IntronlO- + AUUUGGGUAAGUUAUAGAAGUAG 23

4728 23610

CFTR- IntronlO- + UAUUUGGGUAAGUUAUAGAAGUAG 24

4729 23611

921

5535.1 CFTR- IntronlO- + CCUCAGCCUCCCGAGUAG 18

4730 23612

CFTR- IntronlO- + GCCUCAGCCUCCCGAGUAG 19

4731 23613

CFTR- IntronlO- + UGCCUCAGCCUCCCGAGUAG 20

4732 23614

CFTR- IntronlO- + CUGCCUCAGCCUCCCGAGUAG 21

4733 23615

CFTR- IntronlO- + CCUGCCUCAGCCUCCCGAGUAG 22

4734 23616

CFTR- IntronlO- + UCCUGCCUCAGCCUCCCGAGUAG 23

4735 23617

CFTR- IntronlO- + CUCCUGCCUCAGCCUCCCGAGUAG 24

4736 23618

CFTR- IntronlO- + CUGACUAAAACUGAGUAG 18

4737 23619

CFTR- IntronlO- + ACUGACUAAAACUGAGUAG 19

4738 23620

CFTR- IntronlO- + UACUGACUAAAACUGAGUAG 20

4739 23621

CFTR- IntronlO- + CUACUGACUAAAACUGAGUAG 21

4740 23622

CFTR- IntronlO- + ACUACUGACUAAAACUGAGUAG 22

4741 23623

CFTR- IntronlO- + UACUACUGACUAAAACUGAGUAG 23

4742 23624

CFTR- IntronlO- + AUACUACUGACUAAAACUGAGUAG 24

4743 23625

922

5535.1 CFTR- IntronlO- + U AG AAG G AAAG G AG G U AG 18

4744 23626

CFTR- IntronlO- + G U AG AAGG AAAGG AGG U AG 19

4745 23627

CFTR- IntronlO- + AGUAGAAGGAAAGGAGGUAG 20

4746 23628

CFTR- IntronlO- + GAGUAGAAGGAAAGGAGGUAG 21

4747 23629

CFTR- IntronlO- + UGAGUAGAAGGAAAGGAGGUAG 22

4748 23630

CFTR- IntronlO- + CUGAGUAGAAGGAAAGGAGGUAG 23

4749 23631

CFTR- IntronlO- + ACUGAGUAGAAGGAAAGGAGGUAG 24

4750 23632

CFTR- IntronlO- + AGGGAGAAAUGUAUGUAG 18

4751 23633

CFTR- IntronlO- + CAGGGAGAAAUGUAUGUAG 19

4752 23634

CFTR- IntronlO- + ACAGGGAGAAAUGUAUGUAG 20

4753 23635

CFTR- IntronlO- + AACAGGGAGAAAUGUAUGUAG 21

4754 23636

CFTR- IntronlO- + UAA CAGGGAGAAAUGUAUGUAG 22

4755 23637

CFTR- IntronlO- + AUAACAGGGAGAAAUGUAUGUAG 23

4756 23638

CFTR- IntronlO- + AAUAACAGGGAGAAAUGUAUGUAG 24

4757 23639

923

5535.1 CFTR- IntronlO- + AAAAAU ACAAAAAAU U AG 18

4758 23640

CFTR- IntronlO- + U AAAAAU ACAAAAAAU U AG 19

4759 23641

CFTR- IntronlO- + CU AAAAAU ACAAAAAAU U AG 20

4760 23642

CFTR- IntronlO- + ACU AAAAAU ACAAAAAAU U AG 21

4761 23643

CFTR- IntronlO- + U ACU AAAAAU ACAAAAAAU U AG 22

4762 23644

CFTR- IntronlO- + CU ACU AAAAAU ACAAAAAAU U AG 23

4763 23645

CFTR- IntronlO- + UCUACUAAAAAUACAAAAAAUUAG 24

4764 23646

CFTR- IntronlO- + AAGCUUGUUUGGUUUUAG 18

4765 23647

CFTR- IntronlO- + AAAGCUUGUUUGGUUUUAG 19

4766 23648

CFTR- IntronlO- + GAAAGCUUGUUUGGUUUUAG 20

4767 23649

CFTR- IntronlO- + GGAAAGCUUGUUUGGUUUUAG 21

4768 23650

CFTR- IntronlO- + UGGAAAGCUUGUUUGGUUUUAG 22

4769 23651

CFTR- IntronlO- + AUGGAAAGCUUGUUUGGUUUUAG 23

4770 23652

CFTR- IntronlO- + CAUGGAAAGCUUGUUUGGUUUUAG 24

4771 23653

924

5535.1 CFTR- IntronlO- + AAUUUUUUGUAUUUUUAG 18

4772 23654

CFTR- IntronlO- + UAAUUUUUUGUAUUUUUAG 19

4773 23655

CFTR- IntronlO- + CUAAUUUUUUGUAUUUUUAG 20

4774 23656

CFTR- IntronlO- + GCUAAUUUUUUGUAUUUUUAG 21

4775 23657

CFTR- IntronlO- + GGCUAAUUUUUUGUAUUUUUAG 22

4776 23658

CFTR- IntronlO- + UGGCUAAUUUUUUGUAUUUUUAG 23

4777 23659

CFTR- IntronlO- + CUGGCUAAUUUUUUGUAUUUUUAG 24

4778 23660

CFTR- IntronlO- + ACCAUCCCGGCUAAAACG 18

4779 23661

CFTR- IntronlO- + GACCAUCCCGGCUAAAACG 19

4780 23662

CFTR- IntronlO- + AGACCAUCCCGGCUAAAACG 20

4781 23663

CFTR- IntronlO- + GAGACCAUCCCGGCUAAAACG 21

4782 23664

CFTR- IntronlO- + CGAGACCAUCCCGGCUAAAACG 22

4783 23665

CFTR- IntronlO- + UCGAGACCAUCCCGGCUAAAACG 23

4784 23666

CFTR- IntronlO- + AUCGAGACCAUCCCGGCUAAAACG 24

4785 23667

925

5535.1 CFTR- IntronlO- + AAAAAC AACAAAAAAG CG 18

4786 23668

CFTR- IntronlO- + G A AAAACAAC AAAAAAG CG 19

4787 23669

CFTR- IntronlO- + AG AAAAAC AACAAAAAAG CG 20

4788 23670

CFTR- IntronlO- + U AG AAAAAC AACAAAAAAG CG 21

4789 23671

CFTR- IntronlO- + CUAGAAAAACAACAAAAAAGCG 22

4790 23672

CFTR- IntronlO- + ACUAGAAAAACAACAAAAAAGCG 23

4791 23673

CFTR- IntronlO- + AACUAGAAAAACAACAAAAAAGCG 24

4792 23674

CFTR- IntronlO- + GCAAAGAGUGCAUAAAGG 18

4793 23675

CFTR- IntronlO- + AG C A A AG AG U G C A U A A AG G 19

4794 23676

CFTR- IntronlO- + AAGCAAAGAGUGCAUAAAGG 20

4795 23677

CFTR- IntronlO- + AAAG CAAAG AG UG CAU AAAGG 21

4796 23678

CFTR- IntronlO- + U A A AG C A A AG AG U G C A U A A AG G 22

4797 23679

CFTR- IntronlO- + CUAAAGCAAAGAGUGCAUAAAGG 23

4798 23680

CFTR- IntronlO- + CCUAAAGCAAAGAGUGCAUAAAGG 24

4799 23681

926

5535.1 CFTR- IntronlO- + UAUAAGAAAUGAAACAGG 18

4800 23682

CFTR- IntronlO- + AUAUAAGAAAUGAAACAGG 19

4801 23683

CFTR- IntronlO- + GAUAUAAGAAAUGAAACAGG 20

4802 23684

CFTR- IntronlO- + CGAUAUAAGAAAUGAAACAGG 21

4803 23685

CFTR- IntronlO- + ACGAUAUAAGAAAUGAAACAGG 22

4804 23686

CFTR- IntronlO- + UACGAUAUAAGAAAUGAAACAGG 23

4805 23687

CFTR- IntronlO- + AUACGAUAUAAGAAAUGAAACAGG 24

4806 23688

CFTR- IntronlO- + CCUAUAAGGAAUAACAGG 18

4807 23689

CFTR- IntronlO- + ACCUAUAAGGAAUAACAGG 19

4808 23690

CFTR- IntronlO- + AACCUAUAAGGAAUAACAGG 20

4809 23691

CFTR- IntronlO- + GAACCUAUAAGGAAUAACAGG 21

4810 23692

CFTR- IntronlO- + AGAACCUAUAAGGAAUAACAGG 22

4811 23693

CFTR- IntronlO- + CAGAACCUAUAAGGAAUAACAGG 23

4812 23694

CFTR- IntronlO- + ACAGAACCUAUAAGGAAUAACAGG 24

4813 23695

927

5535.1 CFTR- IntronlO- + AGUAGAAACCUAAUCAGG 18

4814 23696

CFTR- IntronlO- + UAGUAGAAACCUAAUCAGG 19

4815 23697

CFTR- IntronlO- + UUAGUAGAAACCUAAUCAGG 20

4816 23698

CFTR- IntronlO- + UUUAGUAGAAACCUAAUCAGG 21

4817 23699

CFTR- IntronlO- + UUUUAGUAGAAACCUAAUCAGG 22

4818 23700

CFTR- IntronlO- + G U U U U AG U AG AAACCU AAU CAGG 23

4819 23701

CFTR- IntronlO- + GG U U U U AG U AG AAACCU AAU CAGG 24

4820 23702

CFTR- IntronlO- + GAAAGGAGGUAGCAGAGG 18

4821 23703

CFTR- IntronlO- + GGAAAGGAGGUAGCAGAGG 19

4822 23704

CFTR- IntronlO- + AGGAAAGGAGGUAGCAGAGG 20

4823 23705

CFTR- IntronlO- + AAGGAAAGGAGGUAGCAGAGG 21

4824 23706

CFTR- IntronlO- + GAAGGAAAGGAGGUAGCAGAGG 22

4825 23707

CFTR- IntronlO- + AGAAGGAAAGGAGGUAGCAGAGG 23

4826 23708

CFTR- IntronlO- + UAGAAGGAAAGGAGGUAGCAGAGG 24

4827 23709

928

5535.1 CFTR- IntronlO- + GUUACAUAAAAAGAGAGG 18

4828 23710

CFTR- IntronlO- + UGUU ACAU AAAAAG AGAGG 19

4829 23711

CFTR-

+ UUGUU ACAU AAAAAG AGAGG 20

lntronlO-469 19355

CFTR- IntronlO- + AUUGUUACAUAAAAAGAGAGG 21

4830 23712

CFTR- IntronlO- + UAUUGUUACAUAAAAAGAGAGG 22

4831 23713

CFTR- IntronlO- + AU AU UG U U ACAU AAAAAG AG AGG 23

4832 23714

CFTR- IntronlO- + CAU AU UG U U ACAU AAAAAG AG AGG 24

4833 23715

CFTR- IntronlO- + UGGCGUGAACCCGGGAGG 18

4834 23716

CFTR- IntronlO- + AUGGCGUGAACCCGGGAGG 19

4835 23717

CFTR- IntronlO- + AAUGGCGUGAACCCGGGAGG 20

1287 20172

CFTR- IntronlO- + GAAUGGCGUGAACCCGGGAGG 21

4836 23718

CFTR- IntronlO- + AGAAUGGCGUGAACCCGGGAGG 22

4837 23719

CFTR- IntronlO- + GAGAAUGGCGUGAACCCGGGAGG 23

4838 23720

CFTR- IntronlO- + GGAGAAUGGCGUGAACCCGGGAGG 24

4839 23721

CFTR-

+ UUGCUUGAGCCCGGGAGG 18

IntronlO- 23722

929

5535.1 4840

CFTR- IntronlO- + AUUGCUUGAGCCCGGGAGG 19

4841 23723

CFTR- IntronlO- + AAUUGCUUGAGCCCGGGAGG 20

4842 23724

CFTR- IntronlO- + GAAUUGCUUGAGCCCGGGAGG 21

4843 23725

CFTR- IntronlO- + AGAAUUGCUUGAGCCCGGGAGG 22

4844 23726

CFTR- IntronlO- + GAGAAUUGCUUGAGCCCGGGAGG 23

4845 23727

CFTR- IntronlO- + GGAGAAUUGCUUGAGCCCGGGAGG 24

4846 23728

CFTR- IntronlO- + UCCCAGCUACUUGGGAGG 18

4847 23729

CFTR- IntronlO- + GUCCCAGCUACUUGGGAGG 19

4848 23730

CFTR- IntronlO- + AGUCCCAGCUACUUGGGAGG 20

4849 23731

CFTR- IntronlO- + UAGUCCCAGCUACUUGGGAGG 21

4850 23732

CFTR- IntronlO- + GUAGUCCCAGCUACUUGGGAGG 22

4851 23733

CFTR- IntronlO- + UGUAGUCCCAGCUACUUGGGAGG 23

4852 23734

CFTR- IntronlO- + CUGUAGUCCCAGCUACUUGGGAGG 24

4853 23735

CFTR-

+ UCCCAACACUUUGGGAGG 18

IntronlO- 23736

930

5535.1 4854

CFTR- IntronlO- + AUCCCAACACUUUGGGAGG 19

4855 23737

CFTR- IntronlO- + AAUCCCAACACUUUGGGAGG 20

4856 23738

CFTR- IntronlO- + UAAUCCCAACACUUUGGGAGG 21

4857 23739

CFTR- IntronlO- + GU AAUCCCAACACUUUGGGAGG 22

4858 23740

CFTR- IntronlO- + UGUAAUCCCAACACUUUGGGAGG 23

4859 23741

CFTR- IntronlO- + CUGUAAUCCCAACACUUUGGGAGG 24

4860 23742

CFTR- IntronlO- + ACCCAGCACUUUGGGAGG 18

4861 23743

CFTR- IntronlO- + AACCCAGCACUUUGGGAGG 19

4862 23744

CFTR- IntronlO- + AAACCCAGCACUUUGGGAGG 20

4863 23745

CFTR- IntronlO- + UAAACCCAGCACUUUGGGAGG 21

4864 23746

CFTR- IntronlO- + AUAAACCCAGCACUUUGGGAGG 22

4865 23747

CFTR- IntronlO- + UAUAAACCCAGCACUUUGGGAGG 23

4866 23748

CFTR- IntronlO- + CUAUAAACCCAGCACUUUGGGAGG 24

4867 23749

CFTR-

+ UCCCAGCACUUUGGGAGG 18

IntronlO- 23750

931

5535.1 4868

CFTR- IntronlO- + AUCCCAGCACUUUGGGAGG 19

4869 23751

CFTR- IntronlO- + AAUCCCAGCACUUUGGGAGG 20

4870 23752

CFTR- IntronlO- + UAAUCCCAGCACUUUGGGAGG 21

4871 23753

CFTR- IntronlO- + GU AAUCCCAGCACUUUGGGAGG 22

4872 23754

CFTR- IntronlO- + UGUAAUCCCAGCACUUUGGGAGG 23

4873 23755

CFTR- IntronlO- + CUGUAAUCCCAGCACUUUGGGAGG 24

4874 23756

CFTR- IntronlO- + UUCUCACAGUUCUGGAGG 18

4875 23757

CFTR- IntronlO- + UUUCUCACAGUUCUGGAGG 19

4876 23758

CFTR- IntronlO- + AUUUCUCACAGUUCUGGAGG 20

4877 23759

CFTR- IntronlO- + UAUUUCUCACAGUUCUGGAGG 21

4878 23760

CFTR- IntronlO- + UUAUUUCUCACAGUUCUGGAGG 22

4879 23761

CFTR- IntronlO- + UUUAUUUCUCACAGUUCUGGAGG 23

4880 23762

CFTR- IntronlO- + AUUUAUUUCUCACAGUUCUGGAGG 24

4881 23763

CFTR-

+ CAGCUACUUGGGAGGCUGAGG 21

IntronlO- 23764

932

5535.1 4882

CFTR- IntronlO- + CCAGCUACUUGGGAGGCUGAGG 22

4883 23765

CFTR- IntronlO- + CCCAGCUACUUGGGAGGCUGAGG 23

4884 23766

CFTR- IntronlO- + UCCCAGCUACUUGGGAGGCUGAGG 24

4885 23767

CFTR- IntronlO- + CUACUUGGGAGGGUGAGG 18

4886 23768

CFTR- IntronlO- + GCUACUUGGGAGGGUGAGG 19

4887 23769

CFTR- IntronlO- + AGCUACUUGGGAGGGUGAGG 20

4888 23770

CFTR- IntronlO- + CAGCUACUUGGGAGGGUGAGG 21

4889 23771

CFTR- IntronlO- + CCAGCUACUUGGGAGGGUGAGG 22

4890 23772

CFTR- IntronlO- + CCCAGCUACUUGGGAGGGUGAGG 23

4891 23773

CFTR- IntronlO- + UCCCAGCUACUUGGGAGGGUGAGG 24

4892 23774

CFTR- IntronlO- + GGUUAAGUUGUUCUUAGG 18

4893 23775

CFTR- IntronlO- + AGGUUAAGUUGUUCUUAGG 19

4894 23776

CFTR- IntronlO- + CAGGUUAAGUUGUUCUUAGG 20

4895 23777

CFTR-

+ CCAGGUUAAGUUGUUCUUAGG 21

IntronlO- 23778

933

5535.1 4896

CFTR- IntronlO- + GCCAGGUUAAGUUGUUCUUAGG 22

4897 23779

CFTR- IntronlO- + UGCCAGGUUAAGUUGUUCUUAGG 23

4898 23780

CFTR- IntronlO- + AUGCCAGGUUAAGUUGUUCUUAGG 24

4899 23781

CFTR- IntronlO- + CUCACAUGGCAGAAAGGG 18

4900 23782

CFTR- IntronlO- + UCUCACAUGGCAGAAAGGG 19

4901 23783

CFTR- IntronlO- + UUCUCACAUGGCAGAAAGGG 20

4902 23784

CFTR- IntronlO- + GUUCUCACAUGGCAGAAAGGG 21

4903 23785

CFTR- IntronlO- + UGUUCUCACAUGGCAGAAAGGG 22

4904 23786

CFTR- IntronlO- + GUGUUCUCACAUGGCAGAAAGGG 23

4905 23787

CFTR- IntronlO- + UGUGUUCUCACAUGGCAGAAAGGG 24

4906 23788

CFTR- IntronlO- + AACAUAUGAAUGGCAGGG 18

4907 23789

CFTR- IntronlO- + CAACAUAUGAAUGGCAGGG 19

4908 23790

CFTR- IntronlO- + UCAACAUAUGAAUGGCAGGG 20

4909 23791

CFTR-

+ UUCAACAUAUGAAUGGCAGGG 21

IntronlO- 23792

934

5535.1 4910

CFTR- IntronlO- + UUUCAACAUAUGAAUGGCAGGG 22

4911 23793

CFTR- IntronlO- + AUUUCAACAUAUGAAUGGCAGGG 23

4912 23794

CFTR- IntronlO- + GAUUUCAACAUAUGAAUGGCAGGG 24

4913 23795

CFTR- IntronlO- + UUGGUACAAAUUUCAGGG 18

4914 23796

CFTR- IntronlO- + AUUGGUACAAAUUUCAGGG 19

4915 23797

CFTR- IntronlO- + AAUUGGUACAAAUUUCAGGG 20

4916 23798

CFTR- IntronlO- + GAAUUGGUACAAAUUUCAGGG 21

4917 23799

CFTR- IntronlO- + CGAAUUGGUACAAAUUUCAGGG 22

4918 23800

CFTR- IntronlO- + ACGAAUUGGUACAAAUUUCAGGG 23

4919 23801

CFTR- IntronlO- + UACGAAUUGGUACAAAUUUCAGGG 24

4920 23802

CFTR- IntronlO- + AUUUCAACAUAUGAAUGG 18

4921 23803

CFTR- IntronlO- + GAUUUCAACAUAUGAAUGG 19

4922 23804

CFTR- IntronlO- + GGAUUUCAACAUAUGAAUGG 20

4923 23805

CFTR-

+ AGGAUUUCAACAUAUGAAUGG 21

IntronlO- 23806

935

5535.1 4924

CFTR- IntronlO- + UAGGAUUUCAACAUAUGAAUGG 22

4925 23807

CFTR- IntronlO- + UUAGGAUUUCAACAUAUGAAUGG 23

4926 23808

CFTR- IntronlO- + AUUAGGAUUUCAACAUAUGAAUGG 24

4927 23809

CFTR- IntronlO- + UGCUGUGUUCUCACAUGG 18

4928 23810

CFTR- IntronlO- + CUGCUGUGUUCUCACAUGG 19

4929 23811

CFTR- IntronlO- + CCUGCUGUGUUCUCACAUGG 20

4930 23812

CFTR- IntronlO- + UCCUGCUGUGUUCUCACAUGG 21

4931 23813

CFTR- IntronlO- + UUCCUGCUGUGUUCUCACAUGG 22

4932 23814

CFTR- IntronlO- + CUUCCUGCUGUGUUCUCACAUGG 23

4933 23815

CFTR- IntronlO- + UCUUCCUGCUGUGUUCUCACAUGG 24

4934 23816

CFTR- IntronlO- + AUUGGCUACCUUGGUUGG 18

4935 23817

CFTR- IntronlO- + GAUUGGCUACCUUGGUUGG 19

4936 23818

CFTR- IntronlO- + GGAUUGGCUACCUUGGUUGG 20

4937 23819

CFTR-

+ UGGAUUGGCUACCUUGGUUGG 21

IntronlO- 23820

936

5535.1 CFTR- IntronlO- + CUGGAUUGGCUACCUUGGUUGG 22

4939 23821

CFTR- IntronlO- + CCUGGAUUGGCUACCUUGGUUGG 23

4940 23822

CFTR- IntronlO- + ACCUGGAUUGGCUACCUUGGUUGG 24

4941 23823

CFTR- IntronlO- + UGGUUGGAUGAGGGAAUG 18

4942 23824

CFTR- IntronlO- + UUGGUUGGAUGAGGGAAUG 19

4943 23825

CFTR- IntronlO- + CUUGGUUGGAUGAGGGAAUG 20

4944 23826

CFTR- IntronlO- + CCUUGGUUGGAUGAGGGAAUG 21

4945 23827

CFTR- IntronlO- + ACCUUGGUUGGAUGAGGGAAUG 22

4946 23828

CFTR- IntronlO- + UACCUUGGUUGGAUGAGGGAAUG 23

4947 23829

CFTR- IntronlO- + CUACCUUGGUUGGAUGAGGGAAUG 24

4948 23830

CFTR- IntronlO- + GAAAGCAGUGUUAUAAUG 18

4949 23831

CFTR- IntronlO- + UGAAAGCAGUGUUAUAAUG 19

4950 23832

CFTR- IntronlO- + CUGAAAGCAGUGUUAUAAUG 20

4951 23833

CFTR-

+ CCUGAAAGCAGUGUUAUAAUG 21

IntronlO- 23834

937

5535.1 4952

CFTR- IntronlO- + UCCUGAAAGCAGUGUUAUAAUG 22

4953 23835

CFTR- IntronlO- + CUCCUGAAAGCAGUGUUAUAAUG 23

4954 23836

CFTR- IntronlO- + GCUCCUGAAAGCAGUGUUAUAAUG 24

4955 23837

CFTR- IntronlO- + GGCAUUGCACUAAACAUG 18

4956 23838

CFTR- IntronlO- + UGGCAUUGCACUAAACAUG 19

4957 23839

CFTR- IntronlO- + AUGGCAUUGCACUAAACAUG 20

4958 23840

CFTR- IntronlO- + UAUGGCAUUGCACUAAACAUG 21

4959 23841

CFTR- IntronlO- + UUAUGGCAUUGCACUAAACAUG 22

4960 23842

CFTR- IntronlO- + UUUAUGGCAUUGCACUAAACAUG 23

4961 23843

CFTR- IntronlO- + GUUUAUGGCAUUGCACUAAACAUG 24

4962 23844

CFTR- IntronlO- + ACCAUCCUGGCCAACAUG 18

4963 23845

CFTR- IntronlO- + UACCAUCCUGGCCAACAUG 19

4964 23846

CFTR- IntronlO- + AUACCAUCCUGGCCAACAUG 20

4965 23847

CFTR-

+ AAUACCAUCCUGGCCAACAUG 21

IntronlO- 23848

938

5535.1 4966

CFTR- IntronlO- + CAAUACCAUCCUGGCCAACAUG 22

4967 23849

CFTR- IntronlO- + UCAAUACCAUCCUGGCCAACAUG 23

4968 23850

CFTR- IntronlO- + AUCAAUACCAUCCUGGCCAACAUG 24

4969 23851

CFTR- IntronlO- + A A A AG AUAAGUGAAGAUG 18

4970 23852

CFTR- IntronlO- + AAAAAGAUAAGUGAAGAUG 19

4971 23853

CFTR- IntronlO- + A A A A A AG AUAAGUGAAGAUG 20

4972 23854

CFTR- IntronlO- + GAAAAAAGAUAAGUGAAGAUG 21

4973 23855

CFTR- IntronlO- + AGAAAAAAGAUAAGUGAAGAUG 22

4974 23856

CFTR- IntronlO- + UAGAAAAAAGAUAAGUGAAGAUG 23

4975 23857

CFTR- IntronlO- + GUAGAAAAAAGAUAAGUGAAGAUG 24

4976 23858

CFTR- IntronlO- + GGCUACCUUGGUUGGAUG 18

4977 23859

CFTR- IntronlO- + UGGCUACCUUGGUUGGAUG 19

4978 23860

CFTR-

+ UUGGCUACCUUGGUUGGAUG 20

lntronlO-481 19367

CFTR- IntronlO- + AUUGGCUACCUUGGUUGGAUG 21

4979 23861

939

5535.1 CFTR- IntronlO- + GAUUGGCUACCUUGGUUGGAUG 22

4980 23862

CFTR- IntronlO- + GGAUUGGCUACCUUGGUUGGAUG 23

4981 23863

CFTR- IntronlO- + UGGAUUGGCUACCUUGGUUGGAUG 24

4982 23864

CFTR- IntronlO- + UUCUUAGGGUGGGAUAUG 18

4983 23865

CFTR- IntronlO- + GUUCUUAGGGUGGGAUAUG 19

4984 23866

CFTR- IntronlO- + UGUUCUUAGGGUGGGAUAUG 20

4985 23867

CFTR- IntronlO- + UUGUUCUUAGGGUGGGAUAUG 21

4986 23868

CFTR- IntronlO- + GUUGUUCUUAGGGUGGGAUAUG 22

4987 23869

CFTR- IntronlO- + AGUUGUUCUUAGGGUGGGAUAUG 23

4988 23870

CFTR- IntronlO- + AAGUUGUUCUUAGGGUGGGAUAUG 24

4989 23871

CFTR- IntronlO- + UAAAAGCUGUUUCGUAUG 18

4990 23872

CFTR- IntronlO- + UUAAAAGCUGUUUCGUAUG 19

4991 23873

CFTR- IntronlO- + UUUAAAAGCUGUUUCGUAUG 20

4992 23874

CFTR- IntronlO- + UUUUAAAAGCUGUUUCGUAUG 21

4993 23875

940

5535.1 CFTR- IntronlO- + GUUUUAAAAGCUGUUUCGUAUG 22

4994 23876

CFTR- IntronlO- + UGUUUUAAAAGCUGUUUCGUAUG 23

4995 23877

CFTR- IntronlO- + UUGUUUUAAAAGCUGUUUCGUAUG 24

4996 23878

CFTR- IntronlO- + UAUGUAGGAAAACAACUG 18

4997 23879

CFTR- IntronlO- + GUAUGUAGGAAAACAACUG 19

4998 23880

CFTR- IntronlO- + CGUAUGUAGGAAAACAACUG 20

4999 23881

CFTR- IntronlO- + UCGUAUGUAGGAAAACAACUG 21

5000 23882

CFTR- IntronlO- + UUCGUAUGUAGGAAAACAACUG 22

5001 23883

CFTR- IntronlO- + UUUCGUAUGUAGGAAAACAACUG 23

5002 23884

CFTR- IntronlO- + GUUUCGUAUGUAGGAAAACAACUG 24

5003 23885

CFTR- IntronlO- + GAAACUCCCCACACACUG 18

5004 23886

CFTR- IntronlO- + UGAAACUCCCCACACACUG 19

5005 23887

CFTR- IntronlO- + CUGAAACUCCCCACACACUG 20

5006 23888

CFTR- IntronlO- + ACUGAAACUCCCCACACACUG 21

5007 23889

941

5535.1 CFTR- IntronlO- + GACUGAAACUCCCCACACACUG 22

5008 23890

CFTR- IntronlO- + GGACUGAAACUCCCCACACACUG 23

5009 23891

CFTR- IntronlO- + AGGACUGAAACUCCCCACACACUG 24

5010 23892

CFTR- IntronlO- + GCAAUAUGCAAUUUACUG 18

5011 23893

CFTR- IntronlO- + UGCAAUAUGCAAUUUACUG 19

5012 23894

CFTR- IntronlO- + CUGCAAUAUGCAAUUUACUG 20

5013 23895

CFTR- IntronlO- + ACUGCAAUAUGCAAUUUACUG 21

5014 23896

CFTR- IntronlO- + UACUGCAAUAUGCAAUUUACUG 22

5015 23897

CFTR- IntronlO- + UUACUGCAAUAUGCAAUUUACUG 23

5016 23898

CFTR- IntronlO- + UUUACUGCAAUAUGCAAUUUACUG 24

5017 23899

CFTR- IntronlO- + CAUCUGUUAGUAAUGCUG 18

5018 23900

CFTR- IntronlO- + UCAUCUGUUAGUAAUGCUG 19

5019 23901

CFTR-

+ AUCAUCUGUUAGUAAUGCUG 20

lntronlO-485 19371

CFTR- IntronlO- + UAUCAUCUGUUAGUAAUGCUG 21

5020 23902

CFTR-

+ AUAUCAUCUGUUAGUAAUGCUG 22

IntronlO- 23903

942

5535.1 5021

CFTR- IntronlO- + AAUAUCAUCUGUUAGUAAUGCUG 23

5022 23904

CFTR- IntronlO- + UAAUAUCAUCUGUUAGUAAUGCUG 24

5023 23905

CFTR- IntronlO- + AAUUAGCCGGGCGUAGUG 18

5024 23906

CFTR- IntronlO- + AAAUUAGCCGGGCGUAGUG 19

5025 23907

CFTR- IntronlO- + AAAAUUAGCCGGGCGUAGUG 20

5026 23908

CFTR- IntronlO- + AAAAAUUAGCCGGGCGUAGUG 21

5027 23909

CFTR- IntronlO- + AAAAAAUUAGCCGGGCGUAGUG 22

5028 23910

CFTR- IntronlO- + CAAAAAAUUAGCCGGGCGUAGUG 23

5029 23911

CFTR- IntronlO- + ACAAAAAAUUAGCCGGGCGUAGUG 24

5030 23912

CFTR- IntronlO- + UCUGUUAGUAAUGCUGUG 18

5031 23913

CFTR- IntronlO- + AUCUGUUAGUAAUGCUGUG 19

5032 23914

CFTR-

+ CAUCUGUUAGUAAUGCUGUG 20

lntronlO-490 19376

CFTR- IntronlO- + UCAUCUGUUAGUAAUGCUGUG 21

5033 23915

CFTR- IntronlO- + AUCAUCUGUUAGUAAUGCUGUG 22

5034 23916

943

5535.1 CFTR- IntronlO- + UAUCAUCUGUUAGUAAUGCUGUG 23

5035 23917

CFTR- IntronlO- + AUAUCAUCUGUUAGUAAUGCUGUG 24

5036 23918

CFTR- IntronlO- + AUUCAAAAAAUAUUUGUG 18

5037 23919

CFTR- IntronlO- + UAUUCAAAAAAUAUUUGUG 19

5038 23920

CFTR- IntronlO- + CUAUUCAAAAAAUAUUUGUG 20

5039 23921

CFTR- IntronlO- + UCUAUUCAAAAAAUAUUUGUG 21

5040 23922

CFTR- IntronlO- + AUCUAUUCAAAAAAUAUUUGUG 22

5041 23923

CFTR- IntronlO- + AAUCUAUUCAAAAAAUAUUUGUG 23

5042 23924

CFTR- IntronlO- + UAAUCUAUUCAAAAAAUAUUUGUG 24

5043 23925

CFTR- IntronlO- + CUAUUCAAAAAAUAUUUG 18

5044 23926

CFTR- IntronlO- + UCUAUUCAAAAAAUAUUUG 19

5045 23927

CFTR- IntronlO- + AUCUAUUCAAAAAAUAUUUG 20

1323 20208

CFTR- IntronlO- + AAU CU AU U CAAAAAAU AU U UG 21

5046 23928

CFTR- IntronlO- + UAAUCUAUU CAAAAAAU AU U UG 22

5047 23929

944

5535.1 CFTR- IntronlO- + CUAAUCUAUUCAAAAAAUAUUUG 23

5048 23930

CFTR- IntronlO- + GCUAAUCUAUUCAAAAAAUAUUUG 24

5049 23931

CFTR- IntronlO- + CUUAUAUUUUUAUUUUUG 18

5050 23932

CFTR- IntronlO- + ACUUAUAUUUUUAUUUUUG 19

5051 23933

CFTR- IntronlO- + CACUUAUAUUUUUAUUUUUG 20

5052 23934

CFTR- IntronlO- + CCACUUAUAUUUUUAUUUUUG 21

5053 23935

CFTR- IntronlO- + GCCACUUAUAUUUUUAUUUUUG 22

5054 23936

CFTR- IntronlO- + GGCCACUUAUAUUUUUAUUUUUG 23

5055 23937

CFTR- IntronlO- + AGGCCACUUAUAUUUUUAUUUUUG 24

5056 23938

CFTR- IntronlO- + UUUUGUUUGUGUUUUUUG 18

5057 23939

CFTR- IntronlO- + CUUUUGUUUGUGUUUUUUG 19

5058 23940

CFTR- IntronlO- + UCUUUUGUUUGUGUUUUUUG 20

5059 23941

CFTR- IntronlO- + UUCUUUUGUUUGUGUUUUUUG 21

5060 23942

CFTR- IntronlO- + UUUCUUUUGUUUGUGUUUUUUG 22

5061 23943

945

5535.1 CFTR- IntronlO- + UUUUCUUUUGUUUGUGUUUUUUG 23

5062 23944

CFTR- IntronlO- + AUUUUCUUUUGUUUGUGUUUUUUG 24

5063 23945

CFTR- IntronlO- + CUAAAAUGACAAUCAAAU 18

5064 23946

CFTR- IntronlO- + GCUAAAAUGACAAUCAAAU 19

5065 23947

CFTR-

+ AGCUAAAAUGACAAUCAAAU 20

lntronlO-498 19384

CFTR- IntronlO- + CAGCUAAAAUGACAAUCAAAU 21

5066 23948

CFTR- IntronlO- + ACAGCUAAAAUGACAAUCAAAU 22

5067 23949

CFTR- IntronlO- + CACAGCUAAAAUGACAAUCAAAU 23

5068 23950

CFTR- IntronlO- + CCACAGCUAAAAUGACAAUCAAAU 24

5069 23951

CFTR- IntronlO- + AACAAUACAAAGAUAAAU 18

5070 23952

CFTR- IntronlO- + UAACAAUACAAAGAUAAAU 19

5071 23953

CFTR- IntronlO- + U UAACAAUACAAAGAUAAAU 20

5072 23954

CFTR- IntronlO- + U U UAACAAUACAAAGAUAAAU 21

5073 23955

CFTR- IntronlO- + AU U UAACAAUACAAAGAUAAAU 22

5074 23956

CFTR-

+ G AU U UAACAAUACAAAGAUAAAU 23

IntronlO- 23957

946

5535.1 5075

CFTR- IntronlO- + AG AU U U AACAAU ACAAAG AU AAAU 24

5076 23958

CFTR- IntronlO- + GUUAUAUGUCCUGACAAU 18

5077 23959

CFTR- IntronlO- + UGUUAUAUGUCCUGACAAU 19

5078 23960

CFTR- IntronlO- + AUGUUAUAUGUCCUGACAAU 20

5079 23961

CFTR- IntronlO- + UAUGUUAUAUGUCCUGACAAU 21

5080 23962

CFTR- IntronlO- + AUAUGUUAUAUGUCCUGACAAU 22

5081 23963

CFTR- IntronlO- + AAUAUGUUAUAUGUCCUGACAAU 23

5082 23964

CFTR- IntronlO- + AAAUAUGUUAUAUGUCCUGACAAU 24

5083 23965

CFTR- IntronlO- + GUGCUAUUUAAACAGAAU 18

5084 23966

CFTR- IntronlO- + AGUGCUAUUUAAACAGAAU 19

5085 23967

CFTR- IntronlO- + CAG UG CU AU U U AAACAG AAU 20

5086 23968

CFTR- IntronlO- + CCAGUGCUAUU U AAACAG AAU 21

5087 23969

CFTR- IntronlO- + UCCAGUGCUAUUUAAACAGAAU 22

5088 23970

CFTR-

+ CUCCAGUGCUAUUUAAACAGAAU 23

IntronlO- 23971

947

5535.1 5089

CFTR- IntronlO- + ACU CCAG UG CU AU U U AAACAG AAU 24

5090 23972

CFTR- IntronlO- + GUCCUCUGUGCUUUGAAU 18

5091 23973

CFTR- IntronlO- + AGUCCUCUGUGCUUUGAAU 19

5092 23974

CFTR- IntronlO- + AAGUCCUCUGUGCUUUGAAU 20

5093 23975

CFTR- IntronlO- + CAAGUCCUCUGUGCUUUGAAU 21

5094 23976

CFTR- IntronlO- + GCAAGUCCUCUGUGCUUUGAAU 22

5095 23977

CFTR- IntronlO- + UGCAAGUCCUCUGUGCUUUGAAU 23

5096 23978

CFTR- IntronlO- + GUGCAAGUCCUCUGUGCUUUGAAU 24

5097 23979

CFTR- IntronlO- + CCAAGCAGUAGAAAUAAU 18

5098 23980

CFTR- IntronlO- + UCCAAGCAGUAGAAAUAAU 19

5099 23981

CFTR- IntronlO- + UUCCAAGCAGUAGAAAUAAU 20

5100 23982

CFTR- IntronlO- + A U U C C A AG C AG U AG A A A U A A U 21

5101 23983

CFTR- IntronlO- + AAUUCCAAGCAGUAGAAAUAAU 22

5102 23984

CFTR-

+ AAAUUCCAAGCAGUAGAAAUAAU 23

IntronlO- 23985

948

5535.1 5103

CFTR- IntronlO- + AAAAUUCCAAGCAGUAGAAAUAAU 24

5104 23986

CFTR- IntronlO- + U U U U AG U AG AAACCU AAU 18

5105 23987

CFTR- IntronlO- + GUUUUAGUAGAAACCUAAU 19

5106 23988

CFTR- IntronlO- + GG U U U U AG U AG AAACCU AAU 20

5107 23989

CFTR- IntronlO- + UGGUUUUAGUAGAAACCUAAU 21

5108 23990

CFTR- IntronlO- + UUGGUUUUAGUAGAAACCUAAU 22

5109 23991

CFTR- IntronlO- + UUUGGUUUUAGUAGAAACCUAAU 23

5110 23992

CFTR- IntronlO- + GUUUGGUUUUAGUAGAAACCUAAU 24

5111 23993

CFTR- IntronlO- + GCCUAGAUGAUUAUUAAU 18

5112 23994

CFTR- IntronlO- + AGCCUAGAUGAUUAUUAAU 19

5113 23995

CFTR-

+ CAGCCUAGAUGAUUAUUAAU 20

lntronlO-503 19389

CFTR- IntronlO- + GCAGCCUAGAUGAUUAUUAAU 21

5114 23996

CFTR- IntronlO- + UGCAGCCUAGAUGAUUAUUAAU 22

5115 23997

CFTR- IntronlO- + UUGCAGCCUAGAUGAUUAUUAAU 23

5116 23998

949

5535.1 CFTR- IntronlO- + UUUGCAGCCUAGAUGAUUAUUAAU 24

5117 23999

CFTR- IntronlO- + UUACAAUUCUUAUUACAU 18

5118 24000

CFTR- IntronlO- + UUUACAAUUCUUAUUACAU 19

5119 24001

CFTR- IntronlO- + UUUUACAAUUCUUAUUACAU 20

1333 20218

CFTR- IntronlO- + AUUUUACAAUUCUUAUUACAU 21

5120 24002

CFTR- IntronlO- + AAUUUUACAAUUCUUAUUACAU 22

5121 24003

CFTR- IntronlO- + AAAU U U U ACAAU U CU U AU U ACAU 23

5122 24004

CFTR- IntronlO- + UAAAUUUUACAAUUCUUAUUACAU 24

5123 24005

CFTR- IntronlO- + AGGUAUAGUCAGUCCCAU 18

5124 24006

CFTR- IntronlO- + CAGGUAUAGUCAGUCCCAU 19

5125 24007

CFTR- IntronlO- + ACAGGUAUAGUCAGUCCCAU 20

5126 24008

CFTR- IntronlO- + GACAGGUAUAGUCAGUCCCAU 21

5127 24009

CFTR- IntronlO- + AGACAGGUAUAGUCAGUCCCAU 22

5128 24010

CFTR- IntronlO- + CAGACAGGUAUAGUCAGUCCCAU 23

5129 24011

950

5535.1 CFTR- IntronlO- + CCAGACAGGUAUAGUCAGUCCCAU 24

5130 24012

CFTR- IntronlO- + AACAUAGAGAAAACUCAU 18

5131 24013

CFTR- IntronlO- + AAACAUAGAGAAAACUCAU 19

5132 24014

CFTR- IntronlO- + AAAACAUAGAGAAAACUCAU 20

5133 24015

CFTR- IntronlO- + UAAAACAUAGAGAAAACUCAU 21

5134 24016

CFTR- IntronlO- + AUAAAACAUAGAGAAAACUCAU 22

5135 24017

CFTR- IntronlO- + AAUAAAACAUAGAGAAAACUCAU 23

5136 24018

CFTR- IntronlO- + AAAUAAAACAUAGAGAAAACUCAU 24

5137 24019

CFTR- IntronlO- + CUAUUUUCCCUAUAAGAU 18

5138 24020

CFTR- IntronlO- + ACUAUUUUCCCUAUAAGAU 19

5139 24021

CFTR- IntronlO- + UACUAUUUUCCCUAUAAGAU 20

5140 24022

CFTR- IntronlO- + AUACUAUUUUCCCUAUAAGAU 21

5141 24023

CFTR- IntronlO- + CAUACUAUUUUCCCUAUAAGAU 22

5142 24024

CFTR- IntronlO- + ACAUACUAUUUUCCCUAUAAGAU 23

5143 24025

951

5535.1 CFTR- IntronlO- + GACAUACUAUUUUCCCUAUAAGAU 24

5144 24026

CFTR- IntronlO- + AAUGGAAAAUGGACAGAU 18

5145 24027

CFTR- IntronlO- + GAAUGGAAAAUGGACAGAU 19

5146 24028

CFTR- IntronlO- + AGAAUGGAAAAUGGACAGAU 20

5147 24029

CFTR- IntronlO- + GAGAAUGGAAAAUGGACAGAU 21

5148 24030

CFTR- IntronlO- + GGAGAAUGGAAAAUGGACAGAU 22

5149 24031

CFTR- IntronlO- + AGGAGAAUGGAAAAUGGACAGAU 23

5150 24032

CFTR- IntronlO- + CAGGAGAAUGGAAAAUGGACAGAU 24

5151 24033

CFTR- IntronlO- + UUGUUCUUAGGGUGGGAU 18

5152 24034

CFTR- IntronlO- + GUUGUUCUUAGGGUGGGAU 19

5153 24035

CFTR- IntronlO- + AGUUGUUCUUAGGGUGGGAU 20

5154 24036

CFTR- IntronlO- + AAGUUGUUCUUAGGGUGGGAU 21

5155 24037

CFTR- IntronlO- + UAAGUUGUUCUUAGGGUGGGAU 22

5156 24038

CFTR- IntronlO- + UUAAGUUGUUCUUAGGGUGGGAU 23

5157 24039

952

5535.1 CFTR- IntronlO- + GUUAAGUUGUUCUUAGGGUGGGAU 24

5158 24040

CFTR- IntronlO- + UGGCUACCUUGGUUGGAU 18

5159 24041

CFTR- IntronlO- + UUGGCUACCUUGGUUGGAU 19

5160 24042

CFTR- IntronlO- + AUUGGCUACCUUGGUUGGAU 20

5161 24043

CFTR- IntronlO- + GAUUGGCUACCUUGGUUGGAU 21

5162 24044

CFTR- IntronlO- + GGAUUGGCUACCUUGGUUGGAU 22

5163 24045

CFTR- IntronlO- + UGGAUUGGCUACCUUGGUUGGAU 23

5164 24046

CFTR- IntronlO- + CUGGAUUGGCUACCUUGGUUGGAU 24

5165 24047

CFTR- IntronlO- + AAACAUGAUGAAAAAUAU 18

5166 24048

CFTR- IntronlO- + UAAACAUGAUGAAAAAUAU 19

5167 24049

CFTR- IntronlO- + CUAAACAUGAUGAAAAAUAU 20

5168 24050

CFTR- IntronlO- + ACUAAACAUGAUGAAAAAUAU 21

5169 24051

CFTR- IntronlO- + CACUAAACAUGAUGAAAAAUAU 22

5170 24052

CFTR- IntronlO- + GCACUAAACAUGAUGAAAAAUAU 23

5171 24053

953

5535.1 CFTR- IntronlO- + UGCACUAAACAUGAUGAAAAAUAU 24

5172 24054

CFTR- IntronlO- + UUUGUGUUAACAAAAUAU 18

5173 24055

CFTR- IntronlO- + CUUUGUGUUAACAAAAUAU 19

5174 24056

CFTR-

+ UCUUUGUGUUAACAAAAUAU 20

lntronlO-506 19392

CFTR- IntronlO- + UUCUUUGUGUUAACAAAAUAU 21

5175 24057

CFTR- IntronlO- + GUUCUUUGUGUUAACAAAAUAU 22

5176 24058

CFTR- IntronlO- + UGUUCUUUGUGUUAACAAAAUAU 23

5177 24059

CFTR- IntronlO- + UUGUUCUUUGUGUUAACAAAAUAU 24

5178 24060

CFTR- IntronlO- + GUUGCAAAAAUACGAUAU 18

5179 24061

CFTR- IntronlO- + AGUUGCAAAAAUACGAUAU 19

5180 24062

CFTR- IntronlO- + GAGUUGCAAAAAUACGAUAU 20

5181 24063

CFTR- IntronlO- + GGAGUUGCAAAAAUACGAUAU 21

5182 24064

CFTR- IntronlO- + AGGAGUUGCAAAAAUACGAUAU 22

5183 24065

CFTR- IntronlO- + AAGGAGUUGCAAAAAUACGAUAU 23

5184 24066

CFTR-

+ AAAGGAGUUGCAAAAAUACGAUAU 24

IntronlO- 24067

954

5535.1 5185

CFTR- IntronlO- + AAAAAU U ACAG AACCU AU 18

5186 24068

CFTR- IntronlO- + CAAAAAUUACAGAACCUAU 19

5187 24069

CFTR- IntronlO- + GCAAAAAUUACAGAACCUAU 20

5188 24070

CFTR- IntronlO- + AG CAAAAAUUACAGAACCUAU 21

5189 24071

CFTR- IntronlO- + AAGCAAAAAUU ACAG AACCU AU 22

5190 24072

CFTR- IntronlO- + GAAGCAAAAAUUACAGAACCUAU 23

5191 24073

CFTR- IntronlO- + UGAAGCAAAAAUUACAGAACCUAU 24

5192 24074

CFTR- IntronlO- + AAAUGCUUGACCACUUAU 18

5193 24075

CFTR- IntronlO- + CAAAUGCUUGACCACUUAU 19

5194 24076

CFTR-

+ ACAAAUGCUUGACCACUUAU 20

lntronlO-508 19394

CFTR- IntronlO- + CACAAAUGCUUGACCACUUAU 21

5195 24077

CFTR- IntronlO- + ACA CAAAUGCUUGACCACUUAU 22

5196 24078

CFTR- IntronlO- + UACACAAAUGCUUGACCACUUAU 23

5197 24079

CFTR- IntronlO- + GUACACAAAUGCUUGACCACUUAU 24

5198 24080

955

5535.1 CFTR- IntronlO- + AAAAAGCACUGAUUUUAU 18

5199 24081

CFTR- IntronlO- + GAAAAAGCACUGAUUUUAU 19

5200 24082

CFTR- IntronlO- + CGAAAAAGCACUGAUUUUAU 20

5201 24083

CFTR- IntronlO- + UCGAAAAAGCACUGAUUUUAU 21

5202 24084

CFTR- IntronlO- + CUCGAAAAAGCACUGAUUUUAU 22

5203 24085

CFTR- IntronlO- + CCUCGAAAAAGCACUGAUUUUAU 23

5204 24086

CFTR- IntronlO- + ACCUCGAAAAAGCACUGAUUUUAU 24

5205 24087

CFTR- IntronlO- + ACAAAG AU U U AU AU AACU 18

5206 24088

CFTR- IntronlO- + AACAAAG AU U U AU AU AACU 19

5207 24089

CFTR- IntronlO- + G AACAAAG AU U U AU AU AACU 20

5208 24090

CFTR- IntronlO- + U G AACAAAG AU U U AU AU AACU 21

5209 24091

CFTR- IntronlO- + G UG AACAAAG AU U U AU AU AACU 22

5210 24092

CFTR- IntronlO- + AG UG AACAAAG AU U U AU AU AACU 23

5211 24093

CFTR- IntronlO- + CAGUGAACAAAGAUUUAUAUAACU 24

5212 24094

956

5535.1 CFTR- IntronlO- + GCCUGUAAUCCCAACACU 18

5213 24095

CFTR- IntronlO- + UGCCUGUAAUCCCAACACU 19

5214 24096

CFTR- IntronlO- + AUGCCUGUAAUCCCAACACU 20

5215 24097

CFTR- IntronlO- + CAUGCCUGUAAUCCCAACACU 21

5216 24098

CFTR- IntronlO- + UCAUGCCUGUAAUCCCAACACU 22

5217 24099

CFTR- IntronlO- + CUCAUGCCUGUAAUCCCAACACU 23

5218 24100

CFTR- IntronlO- + GCUCAUGCCUGUAAUCCCAACACU 24

5219 24101

CFTR- IntronlO- + GCCUAUAAACCCAGCACU 18

5220 24102

CFTR- IntronlO- + UGCCUAUAAACCCAGCACU 19

5221 24103

CFTR- IntronlO- + AUGCCUAUAAACCCAGCACU 20

5222 24104

CFTR- IntronlO- + CAUGCCUAUAAACCCAGCACU 21

5223 24105

CFTR- IntronlO- + UCAUGCCUAUAAACCCAGCACU 22

5224 24106

CFTR- IntronlO- + CUCAUGCCUAUAAACCCAGCACU 23

5225 24107

CFTR- IntronlO- + GCUCAUGCCUAUAAACCCAGCACU 24

5226 24108

957

5535.1 CFTR- IntronlO- + GCCUGUAAUCCCAGCACU 18

5227 24109

CFTR- IntronlO- + CGCCUGUAAUCCCAGCACU 19

5228 24110

CFTR- IntronlO- + ACGCCUGUAAUCCCAGCACU 20

5229 24111

CFTR- IntronlO- + CACGCCUGUAAUCCCAGCACU 21

5230 24112

CFTR- IntronlO- + UCACGCCUGUAAUCCCAGCACU 22

5231 24113

CFTR- IntronlO- + CUCACGCCUGUAAUCCCAGCACU 23

5232 24114

CFTR- IntronlO- + GCUCACGCCUGUAAUCCCAGCACU 24

5233 24115

CFTR- IntronlO- + UCCCGAGUAGCUGGGACU 18

5234 24116

CFTR- IntronlO- + CUCCCGAGUAGCUGGGACU 19

5235 24117

CFTR- IntronlO- + CCUCCCGAGUAGCUGGGACU 20

5236 24118

CFTR- IntronlO- + GCCUCCCGAGUAGCUGGGACU 21

5237 24119

CFTR- IntronlO- + AGCCUCCCGAGUAGCUGGGACU 22

5238 24120

CFTR- IntronlO- + CAGCCUCCCGAGUAGCUGGGACU 23

5239 24121

CFTR- IntronlO- + UCAGCCUCCCGAGUAGCUGGGACU 24

5240 24122

958

5535.1 CFTR- IntronlO- + CCUGUAGUCCCAGCUACU 18

5241 17604

CFTR- IntronlO- + GCCUGUAGUCCCAGCUACU 19

5242 17605

CFTR- IntronlO- + CGCCUGUAGUCCCAGCUACU 20

1344 20229

CFTR- IntronlO- + GCGCCUGUAGUCCCAGCUACU 21

5243 24123

CFTR- IntronlO- + GGCGCCUGUAGUCCCAGCUACU 22

5244 24124

CFTR- IntronlO- + GGGCGCCUGUAGUCCCAGCUACU 23

5245 24125

CFTR- IntronlO- + CGGGCGCCUGUAGUCCCAGCUACU 24

5246 24126

CFTR- IntronlO- + UGCCUGUAGUCCCAGCUACU 20

1345 17606

CFTR- IntronlO- + CGUGCCUGUAGUCCCAGCUACU 22

5247 24127

CFTR- IntronlO- + GCGUGCCUGUAGUCCCAGCUACU 23

5248 24128

CFTR- IntronlO- + UGCGUGCCUGUAGUCCCAGCUACU 24

5249 24129

CFTR- IntronlO- + CUUGCUUCACCUGCUACU 18

5250 24130

CFTR- IntronlO- + ACUUGCUUCACCUGCUACU 19

5251 24131

CFTR-

+ CACUUGCUUCACCUGCUACU 20

lntronlO-512 19398

CFTR-

+ GCACUUGCUUCACCUGCUACU 21

IntronlO- 24132

959

5535.1 5252

CFTR- IntronlO- + UGCACUUGCUUCACCUGCUACU 22

5253 24133

CFTR- IntronlO- + UUGCACUUGCUUCACCUGCUACU 23

5254 24134

CFTR- IntronlO- + UUUGCACUUGCUUCACCUGCUACU 24

5255 24135

CFTR- IntronlO- + AAUCUUAUAGAGAUUACU 18

5256 24136

CFTR- IntronlO- + AAAUCUUAUAGAGAUUACU 19

5257 24137

CFTR-

+ AAAAUCUUAUAGAGAUUACU 20

lntronlO-513 19399

CFTR- IntronlO- + CAAAAUCUUAUAGAGAUUACU 21

5258 24138

CFTR- IntronlO- + ACAAAAUCUUAUAGAGAUUACU 22

5259 24139

CFTR- IntronlO- + AACAAAAU CU UAU AG AG AU U ACU 23

5260 24140

CFTR- IntronlO- + UAACAAAAUCUUAUAGAGAUUACU 24

5261 24141

CFTR- IntronlO- + CCUGCAAUACCAUCACCU 18

5262 24142

CFTR- IntronlO- + CCCUGCAAUACCAUCACCU 19

5263 24143

CFTR- IntronlO- + ACCCUGCAAUACCAUCACCU 20

1346 20230

CFTR- IntronlO- + CACCCUGCAAUACCAUCACCU 21

5264 24144

960

5535.1 CFTR- IntronlO- + CCACCCUGCAAUACCAUCACCU 22

5265 24145

CFTR- IntronlO- + CCCACCCUGCAAUACCAUCACCU 23

5266 24146

CFTR- IntronlO- + CCCCACCCUGCAAUACCAUCACCU 24

5267 24147

CFTR- IntronlO- + AACUCAUAAGGGACCGCU 18

5268 24148

CFTR- IntronlO- + AAACUCAUAAGGGACCGCU 19

5269 24149

CFTR-

+ AAAACUCAUAAGGGACCGCU 20

lntronlO-518 19404

CFTR- IntronlO- + GAAAACUCAUAAGGGACCGCU 21

5270 24150

CFTR- IntronlO- + AGAAAACUCAUAAGGGACCGCU 22

5271 24151

CFTR- IntronlO- + GAGAAAACUCAUAAGGGACCGCU 23

5272 24152

CFTR- IntronlO- + AGAGAAAACUCAUAAGGGACCGCU 24

5273 24153

CFTR- IntronlO- + CUCACAGUUCUGGAGGCU 18

5274 24154

CFTR- IntronlO- + UCUCACAGUUCUGGAGGCU 19

5275 24155

CFTR- IntronlO- + UUCUCACAGUUCUGGAGGCU 20

1357 20241

CFTR- IntronlO- + UUUCUCACAGUUCUGGAGGCU 21

5276 24156

CFTR-

+ AUUUCUCACAGUUCUGGAGGCU 22

IntronlO- 24157

961

5535.1 5277

CFTR- IntronlO- + UAUUUCUCACAGUUCUGGAGGCU 23

5278 24158

CFTR- IntronlO- + UUAUUUCUCACAGUUCUGGAGGCU 24

5279 24159

CFTR- IntronlO- + UCAUCUGUUAGUAAUGCU 18

5280 24160

CFTR- IntronlO- + AUCAUCUGUUAGUAAUGCU 19

5281 24161

CFTR- IntronlO- + UAUCAUCUGUUAGUAAUGCU 20

5282 24162

CFTR- IntronlO- + AUAUCAUCUGUUAGUAAUGCU 21

5283 24163

CFTR- IntronlO- + AAUAUCAUCUGUUAGUAAUGCU 22

5284 24164

CFTR- IntronlO- + UAAUAUCAUCUGUUAGUAAUGCU 23

5285 24165

CFTR- IntronlO- + AUAAUAUCAUCUGUUAGUAAUGCU 24

5286 24166

CFTR- IntronlO- + AGCAGAUUUGGGUCUGCU 18

5287 24167

CFTR- IntronlO- + CAGCAGAUUUGGGUCUGCU 19

5288 24168

CFTR- IntronlO- + CCAGCAGAUUUGGGUCUGCU 20

5289 24169

CFTR- IntronlO- + GCCAGCAGAUUUGGGUCUGCU 21

5290 24170

CFTR-

+ UGCCAGCAGAUUUGGGUCUGCU 22

IntronlO- 24171

962

5535.1 5291

CFTR- IntronlO- + GUGCCAGCAGAUUUGGGUCUGCU 23

5292 24172

CFTR- IntronlO- + GGUGCCAGCAGAUUUGGGUCUGCU 24

5293 24173

CFTR- IntronlO- + AUAUAGAGAGAAACAUCU 18

5294 24174

CFTR- IntronlO- + UAUAUAGAGAGAAACAUCU 19

5295 24175

CFTR- IntronlO- + AUAUAUAGAGAGAAACAUCU 20

5296 24176

CFTR- IntronlO- + UAUAUAUAGAGAGAAACAUCU 21

5297 24177

CFTR- IntronlO- + AUAUAUAUAGAGAGAAACAUCU 22

5298 24178

CFTR- IntronlO- + UAUAUAUAUAGAGAGAAACAUCU 23

5299 24179

CFTR- IntronlO- + UUAUAUAUAUAGAGAGAAACAUCU 24

5300 24180

CFTR- IntronlO- + AUAGAGAGAAACAUCUCU 18

5301 24181

CFTR- IntronlO- + UAUAGAGAGAAACAUCUCU 19

5302 24182

CFTR- IntronlO- + AUAUAGAGAGAAACAUCUCU 20

1365 20249

CFTR- IntronlO- + UAUAUAGAGAGAAACAUCUCU 21

5303 24183

CFTR-

+ AUAUAUAGAGAGAAACAUCUCU 22

IntronlO- 24184

963

5535.1 5304

CFTR- IntronlO- + UAUAUAUAGAGAGAAACAUCUCU 23

5305 24185

CFTR- IntronlO- + AUAUAUAUAGAGAGAAACAUCUCU 24

5306 24186

CFTR- IntronlO- + AU U AAU U U U AAAAAU U CU 18

5307 24187

CFTR- IntronlO- + AAU U AAU U U U AAAAAU U CU 19

5308 24188

CFTR- IntronlO- + G AAU U AAU U U U AAAAAU U CU 20

5309 24189

CFTR- IntronlO- + AG AAU U AAU U U U AAAAAU U CU 21

5310 24190

CFTR- IntronlO- + CAG AAU U AAU U U U AAAAAU U CU 22

5311 24191

CFTR- IntronlO- + GCAG AAU U AAU U U U AAAAAU U CU 23

5312 24192

CFTR- IntronlO- + CG CAG AAU U AAU U U U AAAAAU U CU 24

5313 24193

CFTR- IntronlO- + UAAUUUGAACAACAUUCU 18

5314 24194

CFTR- IntronlO- + AUAAUUUGAACAACAUUCU 19

5315 24195

CFTR-

+ AAU AAU U UG AACAACAU U CU 20

lntronlO-527 19413

CFTR- IntronlO- + AAAUAAUUUGAACAACAUUCU 21

5316 24196

CFTR- IntronlO- + GAAAUAAUUUGAACAACAUUCU 22

5317 24197

964

5535.1 CFTR- IntronlO- + AG AAAU AAU U UG AACAACAU U CU 23

5318 24198

CFTR- IntronlO- + U AG AAAU AAU U UG AACAACAU U CU 24

5319 24199

CFTR- IntronlO- + UUAGUAAACUCCGUUUCU 18

5320 24200

CFTR- IntronlO- + GUUAGUAAACUCCGUUUCU 19

5321 24201

CFTR- IntronlO- + AGUUAGUAAACUCCGUUUCU 20

5322 24202

CFTR- IntronlO- + GAGUUAGUAAACUCCGUUUCU 21

5323 24203

CFTR- IntronlO- + UGAGUUAGUAAACUCCGUUUCU 22

5324 24204

CFTR- IntronlO- + UUGAGUUAGUAAACUCCGUUUCU 23

5325 24205

CFTR- IntronlO- + AUUGAGUUAGUAAACUCCGUUUCU 24

5326 24206

CFTR- IntronlO- + CCUGACAAUAAGAAAAGU 18

5327 24207

CFTR- IntronlO- + UCCUGACAAUAAGAAAAGU 19

5328 24208

CFTR- IntronlO- + GU CCUGACAAUAAGAAAAGU 20

5329 24209

CFTR- IntronlO- + UGUCCUGACAAUAAGAAAAGU 21

5330 24210

CFTR- IntronlO- + AUGUCCUGACAAUAAGAAAAGU 22

5331 24211

965

5535.1 CFTR- IntronlO- + UAUGUCCUGACAAUAAGAAAAGU 23

5332 24212

CFTR- IntronlO- + AUAUGUCCUGACAAUAAGAAAAGU 24

5333 24213

CFTR- IntronlO- + AGUGCUAGGAUUACAAGU 18

5334 24214

CFTR- IntronlO- + AAGUGCUAGGAUUACAAGU 19

5335 24215

CFTR- IntronlO- + AAAGUGCUAGGAUUACAAGU 20

5336 24216

CFTR- IntronlO- + AAAAGUGCUAGGAUUACAAGU 21

5337 24217

CFTR- IntronlO- + C A A A AG UGCUAGGAUUA C A AG U 22

5338 24218

CFTR- IntronlO- + CCAAAAGUGCUAGGAUUACAAGU 23

5339 24219

CFTR- IntronlO- + UCCAAAAGUGCUAGGAUUACAAGU 24

5340 24220

CFTR- IntronlO- + AGGAAAUGGGGUAUAAGU 18

5341 24221

CFTR- IntronlO- + AAGGAAAUGGGGUAUAAGU 19

5342 24222

CFTR- IntronlO- + AAAGGAAAUGGGGUAUAAGU 20

5343 24223

CFTR- IntronlO- + CAAAGGAAAUGGGGUAUAAGU 21

5344 24224

CFTR- IntronlO- + ACAAAGGAAAUGGGGUAUAAGU 22

5345 24225

966

5535.1 CFTR- IntronlO- + AACAAAGGAAAUGGGGUAUAAGU 23

5346 24226

CFTR- IntronlO- + AAACAAAGGAAAUGGGGUAUAAGU 24

5347 24227

CFTR- IntronlO- + ACAGAAAUAU U CAGCAG U 18

5348 24228

CFTR- IntronlO- + GACAGAAAUAU U CAGCAG U 19

5349 24229

CFTR- IntronlO- + AGACAGAAAUAUUCAGCAGU 20

5350 24230

CFTR- IntronlO- + G AG AC AG AAA UAUUCAGCAGU 21

5351 24231

CFTR- IntronlO- + AGAGACAGAAAUAUUCAGCAGU 22

5352 24232

CFTR- IntronlO- + GAGAGACAGAAAUAUUCAGCAGU 23

5353 24233

CFTR- IntronlO- + GGAGAGACAGAAAUAUUCAGCAGU 24

5354 24234

CFTR- IntronlO- + AAAGUUGUCCAAGAUAGU 18

5355 24235

CFTR- IntronlO- + GAAAGUUGUCCAAGAUAGU 19

5356 24236

CFTR-

+ GGAAAGUUGUCCAAGAUAGU 20

lntronlO-120 19006

CFTR- IntronlO- + UGGAAAGUUGUCCAAGAUAGU 21

5357 24237

CFTR- IntronlO- + AUGGAAAGUUGUCCAAGAUAGU 22

5358 24238

CFTR-

+ UAUGGAAAGUUGUCCAAGAUAGU 23

IntronlO- 24239

967

5535.1 5359

CFTR- IntronlO- + AUAUGGAAAGUUGUCCAAGAUAGU 24

5360 24240

CFTR- IntronlO- + CUUUAUCAACAUGAAGGU 18

5361 24241

CFTR- IntronlO- + CCUUUAUCAACAUGAAGGU 19

5362 24242

CFTR- IntronlO- + CCCUUUAUCAACAUGAAGGU 20

5363 24243

CFTR- IntronlO- + ACCCUUUAUCAACAUGAAGGU 21

5364 24244

CFTR- IntronlO- + GACCCUUUAUCAACAUGAAGGU 22

5365 24245

CFTR- IntronlO- + UGACCCUUUAUCAACAUGAAGGU 23

5366 24246

CFTR- IntronlO- + UUGACCCUUUAUCAACAUGAAGGU 24

5367 24247

CFTR- IntronlO- + UGAGGGUCUCUCUAAGGU 18

5368 24248

CFTR- IntronlO- + GUGAGGGUCUCUCUAAGGU 19

5369 24249

CFTR- IntronlO- + GGUGAGGGUCUCUCUAAGGU 20

5370 24250

CFTR- IntronlO- + GGGUGAGGGUCUCUCUAAGGU 21

5371 24251

CFTR- IntronlO- + GGGGUGAGGGUCUCUCUAAGGU 22

5372 24252

CFTR-

+ AGGGGUGAGGGUCUCUCUAAGGU 23

IntronlO- 24253

968

5535.1 5373

CFTR- IntronlO- + AAGGGGUGAGGGUCUCUCUAAGGU 24

5374 24254

CFTR- IntronlO- + UUACAUAAAAAGAGAGGU 18

5375 24255

CFTR- IntronlO- + GUUACAUAAAAAGAGAGGU 19

5376 24256

CFTR-

+ UGUUACAUAAAAAGAGAGGU 20

lntronlO-535 19421

CFTR- IntronlO- + UUGUUACAUAAAAAGAGAGGU 21

5377 24257

CFTR- IntronlO- + AUUGUUACAUAAAAAGAGAGGU 22

5378 24258

CFTR- IntronlO- + U AU UG U U ACAU AAAAAG AG AGG U 23

5379 24259

CFTR- IntronlO- + AU AU UG U U ACAU AAAAAG AG AGG U 24

5380 24260

CFTR- IntronlO- + GCGGGCGGAUCACGAGGU 18

5381 24261

CFTR- IntronlO- + GGCGGGCGGAUCACGAGGU 19

5382 24262

CFTR- IntronlO- + AGGCGGGCGGAUCACGAGGU 20

5383 24263

CFTR- IntronlO- + GAGGCGGGCGGAUCACGAGGU 21

5384 24264

CFTR- IntronlO- + CGAGGCGGGCGGAUCACGAGGU 22

5385 24265

CFTR- IntronlO- + CCGAGGCGGGCGGAUCACGAGGU 23

5386 24266

969

5535.1 CFTR- IntronlO- + GCCGAGGCGGGCGGAUCACGAGGU 24

5387 24267

CFTR- IntronlO- + UAUAUUCUUUUAUGUGGU 18

5388 24268

CFTR- IntronlO- + AUAUAUUCUUUUAUGUGGU 19

5389 24269

CFTR- IntronlO- + AAUAUAUUCUUUUAUGUGGU 20

5390 24270

CFTR- IntronlO- + GAAUAUAUUCUUUUAUGUGGU 21

5391 24271

CFTR- IntronlO- + CGAAUAUAUUCUUUUAUGUGGU 22

5392 24272

CFTR- IntronlO- + ACGAAUAUAUUCUUUUAUGUGGU 23

5393 24273

CFTR- IntronlO- + CACGAAUAUAUUCUUUUAUGUGGU 24

5394 24274

CFTR- IntronlO- + AAAAGCUGUUUCGUAUGU 18

5395 24275

CFTR- IntronlO- + UAAAAGCUGUUUCGUAUGU 19

5396 24276

CFTR-

+ UUAAAAGCUGUUUCGUAUGU 20

lntronlO-539 19425

CFTR- IntronlO- + UUUAAAAGCUGUUUCGUAUGU 21

5397 24277

CFTR- IntronlO- + UUUUAAAAGCUGUUUCGUAUGU 22

5398 24278

CFTR- IntronlO- + GUUUUAAAAGCUGUUUCGUAUGU 23

5399 24279

CFTR-

+ UGUUUUAAAAGCUGUUUCGUAUGU 24

IntronlO- 24280

970

5535.1 5400

CFTR- IntronlO- + AUCUGUUAGUAAUGCUGU 18

5401 24281

CFTR- IntronlO- + CAUCUGUUAGUAAUGCUGU 19

5402 24282

CFTR-

+ UCAUCUGUUAGUAAUGCUGU 20

lntronlO-540 19426

CFTR- IntronlO- + AUCAUCUGUUAGUAAUGCUGU 21

5403 24283

CFTR- IntronlO- + UAUCAUCUGUUAGUAAUGCUGU 22

5404 24284

CFTR- IntronlO- + AUAUCAUCUGUUAGUAAUGCUGU 23

5405 24285

CFTR- IntronlO- + AAUAUCAUCUGUUAGUAAUGCUGU 24

5406 24286

CFTR- IntronlO- + AUAGAGACAAGGUGGUGU 18

5407 24287

CFTR- IntronlO- + AAUAGAGACAAGGUGGUGU 19

5408 24288

CFTR- IntronlO- + UAAUAGAGACAAGGUGGUGU 20

5409 24289

CFTR- IntronlO- + AUAAUAGAGACAAGGUGGUGU 21

5410 24290

CFTR- IntronlO- + AAUAAUAGAGACAAGGUGGUGU 22

5411 24291

CFTR- IntronlO- + CAAUAAUAGAGACAAGGUGGUGU 23

5412 24292

CFTR- IntronlO- + UCAAUAAUAGAGACAAGGUGGUGU 24

5413 24293

971

5535.1 CFTR- IntronlO- + G A AAG AAAAU G U U U U U G U 18

5414 24294

CFTR- IntronlO- + AGAAAGAAAAUGUUUUUGU 19

5415 24295

CFTR- IntronlO- + A AG A A AG A A A A UGUUUUUGU 20

5416 24296

CFTR- IntronlO- + UAAGAAAGAAAAUGUUUUUGU 21

5417 24297

CFTR- IntronlO- + UUAAGAAAGAAAAUGUUUUUGU 22

5418 24298

CFTR- IntronlO- + UUUAAGAAAGAAAAUGUUUUUGU 23

5419 24299

CFTR- IntronlO- + U U U U AAG AAAG AAAAUG U U U U UG U 24

5420 24300

CFTR- IntronlO- + UGGCUUAACCCAUCUAUU 18

5421 24301

CFTR- IntronlO- + UUGGCUUAACCCAUCUAUU 19

5422 24302

CFTR- IntronlO- + GUUGGCUUAACCCAUCUAUU 20

5423 24303

CFTR- IntronlO- + AGUUGGCUUAACCCAUCUAUU 21

5424 24304

CFTR- IntronlO- + CAGUUGGCUUAACCCAUCUAUU 22

5425 24305

CFTR- IntronlO- + UCAGUUGGCUUAACCCAUCUAUU 23

5426 24306

CFTR- IntronlO- + UUCAGUUGGCUUAACCCAUCUAUU 24

5427 24307

972

5535.1 CFTR- IntronlO- + AUAAUUCUAGAAAGUAUU 18

5428 24308

CFTR- IntronlO- + UAUAAUUCUAGAAAGUAUU 19

5429 24309

CFTR- IntronlO- + GU AUAAUUCUAGAAAGUAUU 20

5430 24310

CFTR- IntronlO- + GGUAUAAUUCUAGAAAGUAUU 21

5431 24311

CFTR- IntronlO- + CGGUAUAAUUCUAGAAAGUAUU 22

5432 24312

CFTR- IntronlO- + UCGGUAUAAUUCUAGAAAGUAUU 23

5433 24313

CFTR- IntronlO- + UUCGGUAUAAUUCUAGAAAGUAUU 24

5434 24314

CFTR- IntronlO- + UUUAUUUAUUUAUUUAUU 18

5435 24315

CFTR- IntronlO- + AUUUAUUUAUUUAUUUAUU 19

5436 24316

CFTR- IntronlO- + UAUUUAUUUAUUUAUUUAUU 20

5437 24317

CFTR- IntronlO- + UUAUUUAUUUAUUUAUUUAUU 21

5438 24318

CFTR- IntronlO- + UUUAUUUAUUUAUUUAUUUAUU 22

5439 24319

CFTR- IntronlO- + AUUUAUUUAUUUAUUUAUUUAUU 23

5440 24320

CFTR- IntronlO- + UAUUUAUUUAUUUAUUUAUUUAUU 24

5441 24321

973

5535.1 CFTR- IntronlO- + UUUGCUGAUUGCUUUAUU 18

5442 24322

CFTR- IntronlO- + AUUUGCUGAUUGCUUUAUU 19

5443 24323

CFTR- IntronlO- + AAUUUGCUGAUUGCUUUAUU 20

5444 24324

CFTR- IntronlO- + AAAUUUGCUGAUUGCUUUAUU 21

5445 24325

CFTR- IntronlO- + GAAAUUUGCUGAUUGCUUUAUU 22

5446 24326

CFTR- IntronlO- + GGAAAUUUGCUGAUUGCUUUAUU 23

5447 24327

CFTR- IntronlO- + AGGAAAUUUGCUGAUUGCUUUAUU 24

5448 24328

CFTR- IntronlO- + CCUGUAAUCCCAACACUU 18

5449 24329

CFTR- IntronlO- + GCCUGUAAUCCCAACACUU 19

5450 24330

CFTR- IntronlO- + UGCCUGUAAUCCCAACACUU 20

1391 20275

CFTR- IntronlO- + AUGCCUGUAAUCCCAACACUU 21

5451 24331

CFTR- IntronlO- + CAUGCCUGUAAUCCCAACACUU 22

5452 24332

CFTR- IntronlO- + UCAUGCCUGUAAUCCCAACACUU 23

5453 24333

CFTR- IntronlO- + CUCAUGCCUGUAAUCCCAACACUU 24

5454 24334

974

5535.1 CFTR- IntronlO- + CCUAUAAACCCAGCACUU 18

5455 24335

CFTR- IntronlO- + GCCUAUAAACCCAGCACUU 19

5456 24336

CFTR- IntronlO- + UGCCUAUAAACCCAGCACUU 20

1392 20276

CFTR- IntronlO- + AUGCCUAUAAACCCAGCACUU 21

5457 24337

CFTR- IntronlO- + CAUGCCUAUAAACCCAGCACUU 22

5458 24338

CFTR- IntronlO- + UCAUGCCUAUAAACCCAGCACUU 23

5459 24339

CFTR- IntronlO- + CUCAUGCCUAUAAACCCAGCACUU 24

5460 24340

CFTR- IntronlO- + CCUGUAAUCCCAGCACUU 18

5461 24341

CFTR- IntronlO- + GCCUGUAAUCCCAGCACUU 19

5462 24342

CFTR- IntronlO- + CGCCUGUAAUCCCAGCACUU 20

1393 20277

CFTR- IntronlO- + ACGCCUGUAAUCCCAGCACUU 21

5463 24343

CFTR- IntronlO- + CACGCCUGUAAUCCCAGCACUU 22

5464 24344

CFTR- IntronlO- + UCACGCCUGUAAUCCCAGCACUU 23

5465 24345

CFTR- IntronlO- + CUCACGCCUGUAAUCCCAGCACUU 24

5466 24346

975

5535.1 CFTR- IntronlO- + GAACCAUUUUAUAGACUU 18

5467 24347

CFTR- IntronlO- + GGAACCAUUUUAUAGACUU 19

5468 24348

CFTR- IntronlO- + AGGAACCAUUUUAUAGACUU 20

5469 24349

CFTR- IntronlO- + AAGGAACCAUUUUAUAGACUU 21

5470 24350

CFTR- IntronlO- + CAAGGAACCAUUUUAUAGACUU 22

5471 24351

CFTR- IntronlO- + ACAAGGAACCAUUUUAUAGACUU 23

5472 24352

CFTR- IntronlO- + AACAAGGAACCAUUUUAUAGACUU 24

5473 24353

CFTR- IntronlO- + CUGUAGUCCCAGCUACUU 18

5474 24354

CFTR- IntronlO- + CCUGUAGUCCCAGCUACUU 19

5475 24355

CFTR-

+ GCCUGUAGUCCCAGCUACUU 20

lntronlO-720 19606

CFTR- IntronlO- + CGCCUGUAGUCCCAGCUACUU 21

5476 24356

CFTR- IntronlO- + GCGCCUGUAGUCCCAGCUACUU 22

5477 24357

CFTR- IntronlO- + GGCGCCUGUAGUCCCAGCUACUU 23

5478 24358

CFTR- IntronlO- + GGGCGCCUGUAGUCCCAGCUACUU 24

5479 24359

CFTR-

+ UGCCUGUAGUCCCAGCUACUU 21

IntronlO- 24360

976

5535.1 5480

CFTR- IntronlO- + GUGCCUGUAGUCCCAGCUACUU 22

5481 24361

CFTR- IntronlO- + CGUGCCUGUAGUCCCAGCUACUU 23

5482 24362

CFTR- IntronlO- + GCGUGCCUGUAGUCCCAGCUACUU 24

5483 24363

CFTR- IntronlO- + AAUUUAUUUCUCACAGUU 18

5484 24364

CFTR- IntronlO- + GAAUUUAUUUCUCACAGUU 19

5485 24365

CFTR- IntronlO- + GGAAUUUAUUUCUCACAGUU 20

5486 24366

CFTR- IntronlO- + AGGAAUUUAUUUCUCACAGUU 21

5487 24367

CFTR- IntronlO- + CAGGAAUUUAUUUCUCACAGUU 22

5488 24368

CFTR- IntronlO- + ACAGGAAUUUAUUUCUCACAGUU 23

5489 24369

CFTR- IntronlO- + AACAGG AAU U U AU U U CU CACAG U U 24

5490 24370

CFTR- IntronlO- + CUUGACAUCAGUUGGGUU 18

5491 24371

CFTR- IntronlO- + GCUUGACAUCAGUUGGGUU 19

5492 24372

CFTR- IntronlO- + UGCUUGACAUCAGUUGGGUU 20

5493 24373

CFTR-

+ CUGCUUGACAUCAGUUGGGUU 21

IntronlO- 24374

977

5535.1 5494

CFTR- IntronlO- + UCUGCUUGACAUCAGUUGGGUU 22

5495 24375

CFTR- IntronlO- + UUCUGCUUGACAUCAGUUGGGUU 23

5496 24376

CFTR- IntronlO- + CUUCUGCUUGACAUCAGUUGGGUU 24

5497 24377

CFTR- IntronlO- + AAAAU AU ACCCAAAAU U U 18

5498 24378

CFTR- IntronlO- + U AAAAU AU ACCCAAAAU U U 19

5499 24379

CFTR- IntronlO- + AU AAAAU AU ACCCAAAAU U U 20

5500 24380

CFTR- IntronlO- + UAU AAAAU AU ACCCAAAAU U U 21

5501 24381

CFTR- IntronlO- + AUAU AAAAU AU ACCCAAAAU U U 22

5502 24382

CFTR- IntronlO- + AAUAU AAAAU AU ACCCAAAAU U U 23

5503 24383

CFTR- IntronlO- + AAAU AU AAAAU AU ACCCAAAAU U U 24

5504 24384

CFTR- IntronlO- + ACGAAUUGGUACAAAUUU 18

5505 24385

CFTR- IntronlO- + UACGAAUUGGUACAAAUUU 19

5506 24386

CFTR- IntronlO- + GU ACGAAUUGGUACAAAUUU 20

5507 24387

CFTR-

+ AGUACGAAUUGGUACAAAUUU 21

IntronlO- 24388

978

5535.1 5508

CFTR- IntronlO- + GAGUACGAAUUGGUACAAAUUU 22

5509 24389

CFTR- IntronlO- + UGAGUACGAAUUGGUACAAAUUU 23

5510 24390

CFTR- IntronlO- + AUGAGUACGAAUUGGUACAAAUUU 24

5511 24391

CFTR- IntronlO- + CCCUAUUAUUCAACAUUU 18

5512 24392

CFTR- IntronlO- + CCCCUAUUAUUCAACAUUU 19

5513 24393

CFTR- IntronlO- + ACCCCUAUUAUUCAACAUUU 20

5514 24394

CFTR- IntronlO- + AACCCCUAUUAUUCAACAUUU 21

5515 24395

CFTR- IntronlO- + AAACCCCU AU U AU U CAACAU U U 22

5516 24396

CFTR- IntronlO- + CAAACCCCU AU U AU U CAACAU U U 23

5517 24397

CFTR- IntronlO- + UCAAACCCCUAUUAUUCAACAUUU 24

5518 24398

CFTR- IntronlO- + U CU AU U CAAAAAAU AU U U 18

5519 24399

CFTR- IntronlO- + AUCUAUUCAAAAAAUAUUU 19

5520 24400

CFTR- IntronlO- + AAUCUAUUCAAAAAAUAUUU 20

5521 24401

CFTR-

+ UAAUCUAUU CAAAAAAU AU U U 21

IntronlO- 24402

979

5535.1 5522

CFTR- IntronlO- + CUAAUCUAUUCAAAAAAUAUUU 22

5523 24403

CFTR- IntronlO- + GCUAAUCUAUUCAAAAAAUAUUU 23

5524 24404

CFTR- IntronlO- + AGCUAAUCUAUUCAAAAAAUAUUU 24

5525 24405

CFTR- IntronlO- + CGAGUUAUCUCCGUAUUU 18

5526 24406

CFTR- IntronlO- + ACGAGUUAUCUCCGUAUUU 19

5527 24407

CFTR- IntronlO- + CACGAGUUAUCUCCGUAUUU 20

5528 24408

CFTR- IntronlO- + UCACGAGUUAUCUCCGUAUUU 21

5529 24409

CFTR- IntronlO- + GUCACGAGUUAUCUCCGUAUUU 22

5530 24410

CFTR- IntronlO- + AGUCACGAGUUAUCUCCGUAUUU 23

5531 24411

CFTR- IntronlO- + AAGUCACGAGUUAUCUCCGUAUUU 24

5532 24412

CFTR- IntronlO- + CUGUAAUCCCAACACUUU 18

5533 24413

CFTR- IntronlO- + CCUGUAAUCCCAACACUUU 19

5534 24414

CFTR-

+ GCCUGUAAUCCCAACACUUU 20

lntronlO-722 19608

CFTR- IntronlO- + UGCCUGUAAUCCCAACACUUU 21

5535 24415

980

5535.1 CFTR- IntronlO- + AUGCCUGUAAUCCCAACACUUU 22

5536 24416

CFTR- IntronlO- + CAUGCCUGUAAUCCCAACACUUU 23

5537 24417

CFTR- IntronlO- + UCAUGCCUGUAAUCCCAACACUUU 24

5538 24418

CFTR- IntronlO- + CUAUAAACCCAGCACUUU 18

5539 24419

CFTR- IntronlO- + CCUAUAAACCCAGCACUUU 19

5540 24420

CFTR-

+ GCCUAUAAACCCAGCACUUU 20

lntronlO-723 19609

CFTR- IntronlO- + UGCCUAUAAACCCAGCACUUU 21

5541 24421

CFTR- IntronlO- + AUGCCUAUAAACCCAGCACUUU 22

5542 24422

CFTR- IntronlO- + CAUGCCUAUAAACCCAGCACUUU 23

5543 24423

CFTR- IntronlO- + UCAUGCCUAUAAACCCAGCACUUU 24

5544 24424

CFTR- IntronlO- + CUGUAAUCCCAGCACUUU 18

5545 24425

CFTR- IntronlO- + CCUGUAAUCCCAGCACUUU 19

5546 24426

CFTR-

+ GCCUGUAAUCCCAGCACUUU 20

lntronlO-724 19610

CFTR- IntronlO- + CGCCUGUAAUCCCAGCACUUU 21

5547 24427

CFTR- IntronlO- + ACGCCUGUAAUCCCAGCACUUU 22

5548 24428

981

5535.1 CFTR- IntronlO- + CACGCCUGUAAUCCCAGCACUUU 23

5549 24429

CFTR- IntronlO- + UCACGCCUGUAAUCCCAGCACUUU 24

5550 24430

CFTR- IntronlO- + UGAUAAAUAAUUGCCUUU 18

5551 24431

CFTR- IntronlO- + UUGAUAAAUAAUUGCCUUU 19

5552 24432

CFTR- IntronlO- + AUUGAUAAAUAAUUGCCUUU 20

5553 24433

CFTR- IntronlO- + UAUUGAUAAAUAAUUGCCUUU 21

5554 24434

CFTR- IntronlO- + AUAUUGAUAAAUAAUUGCCUUU 22

5555 24435

CFTR- IntronlO- + GAUAUUGAUAAAUAAUUGCCUUU 23

5556 24436

CFTR- IntronlO- + AGAUAUUGAUAAAUAAUUGCCUUU 24

5557 24437

CFTR- IntronlO- + AAAUAAGCCUUAGUCUUU 18

5558 24438

CFTR- IntronlO- + GAAAUAAGCCUUAGUCUUU 19

5559 24439

CFTR- IntronlO- + AGAAAUAAGCCUUAGUCUUU 20

5560 24440

CFTR- IntronlO- + GAGAAAUAAGCCUUAGUCUUU 21

5561 24441

CFTR- IntronlO- + AG AG AAAU AAGCCU U AG U CU U U 22

5562 24442

982

5535.1 CFTR- IntronlO- + CAG AG AAAU AAGCCU U AG U CU U U 23

5563 24443

CFTR- IntronlO- + CCAGAGAAAUAAGCCUUAGUCUUU 24

5564 24444

CFTR- IntronlO- + AGAAAAUUUGUUUUCUUU 18

5565 24445

CFTR- IntronlO- + AAGAAAAUUUGUUUUCUUU 19

5566 24446

CFTR- IntronlO- + AAAGAAAAUUUGUUUUCUUU 20

5567 24447

CFTR- IntronlO- + CAAAGAAAAUUUGUUUUCUUU 21

5568 24448

CFTR- IntronlO- + ACAAAG AAAAU UUGUUUUCUUU 22

5569 24449

CFTR- IntronlO- + AACAAAGAAAAUUUGUUUUCUUU 23

5570 24450

CFTR- IntronlO- + AAACAAAG AAAAU UUGUUUUCUUU 24

5571 24451

CFTR- IntronlO- + G AAAAAU AAU AACAU U U U 18

5572 24452

CFTR- IntronlO- + AG AAAAAU AAU AACAU U U U 19

5573 24453

CFTR- IntronlO- + AAG AAAAAU AAU AACAU U U U 20

5574 24454

CFTR- IntronlO- + AAAG AAAAAU AAU AACAU U U U 21

5575 24455

CFTR- IntronlO- + AAAAG AAAAAU AAU AACAU U U U 22

5576 24456

983

5535.1 CFTR- IntronlO- + U AAAAG AAAAAU AAU AACAU U U U 23

5577 24457

CFTR- IntronlO- + AU AAAAG AAAAAU AAU AACAU U U U 24

5578 24458

CFTR- IntronlO- + AUACAUACAUAUGAUUUU 18

5579 24459

CFTR- IntronlO- + UAUACAUACAUAUGAUUUU 19

5580 24460

CFTR- IntronlO- + AUAUACAUACAUAUGAUUUU 20

5581 24461

CFTR- IntronlO- + UAUAUACAUACAUAUGAUUUU 21

5582 24462

CFTR- IntronlO- + AUAUAUACAUACAUAUGAUUUU 22

5583 24463

CFTR- IntronlO- + CAUAUAUACAUACAUAUGAUUUU 23

5584 24464

CFTR- IntronlO- + ACAUAUAUACAUACAUAUGAUUUU 24

5585 24465

CFTR- IntronlO- + CACCAAUUUUUUUUUUUU 18

5586 24466

CFTR- IntronlO- + ACACCAAUUUUUUUUUUUU 19

5587 24467

CFTR- IntronlO- + AACACCAAUUUUUUUUUUUU 20

5588 24468

CFTR- IntronlO- + AAACACCAAUUUUUUUUUUUU 21

5589 24469

CFTR- IntronlO- + CAAACACCAAUUUUUUUUUUUU 22

5590 24470

984

5535.1 CFTR- IntronlO- + GCAAACACCAAUUUUUUUUUUUU 23

5591 24471

CFTR- IntronlO- + UGCAAACACCAAUUUUUUUUUUUU 24

5592 24472

CFTR- IntronlO- - UAAAAAUGUUAAUGAAAA 18

5593 24473

CFTR- IntronlO- - GUAAAAAUGUUAAUGAAAA 19

5594 24474

CFTR- IntronlO- - GG UAAAAAUGUUAAUGAAAA 20

5595 24475

CFTR- IntronlO- - AGGUAAAAAUGUUAAUGAAAA 21

5596 24476

CFTR- IntronlO- - UAGGUAAAAAUGUUAAUGAAAA 22

5597 24477

CFTR- IntronlO- - GUAGGUAAAAAUGUUAAUGAAAA 23

5598 24478

CFTR- IntronlO- - UGUAGGUAAAAAUGUUAAUGAAAA 24

5599 24479

CFTR- IntronlO- - AU U U AU UAAAAU U UAAAA 18

5600 24480

CFTR- IntronlO- - U AU U U AU UAAAAU U UAAAA 19

5601 24481

CFTR- IntronlO- - UUAUUUAU UAAAAU U UAAAA 20

5602 24482

CFTR- IntronlO- - AUUAUUUAU UAAAAU U UAAAA 21

5603 24483

CFTR- IntronlO- - UAUUAUUUAU UAAAAU U UAAAA 22

5604 24484

985

5535.1 CFTR- IntronlO- - AUAUUAUUUAU U AAAAU U U AAAA 23

5605 24485

CFTR- IntronlO- - GAUAUUAUUUAU U AAAAU U U AAAA 24

5606 24486

CFTR- IntronlO- - CGAAUAAUCUAAGACAAA 18

5607 24487

CFTR- IntronlO- - CCGAAUAAUCUAAGACAAA 19

5608 24488

CFTR- IntronlO- - ACCGAAUAAUCUAAGACAAA 20

5609 24489

CFTR- IntronlO- - UACCGAAUAAUCUAAGACAAA 21

5610 24490

CFTR- IntronlO- - AUACCGAAUAAUCUAAGACAAA 22

5611 24491

CFTR- IntronlO- - UAUACCGAAUAAUCUAAGACAAA 23

5612 24492

CFTR- IntronlO- - UUAUACCGAAUAAUCUAAGACAAA 24

5613 24493

CFTR- IntronlO- - GCCUAUUUGACAUCCAAA 18

5614 24494

CFTR- IntronlO- - UGCCUAUUUGACAUCCAAA 19

5615 24495

CFTR- IntronlO- - AUGCCUAUUUGACAUCCAAA 20

5616 24496

CFTR- IntronlO- - AAUGCCUAUUUGACAUCCAAA 21

5617 24497

CFTR- IntronlO- - AAAUGCCUAUUUGACAUCCAAA 22

5618 24498

986

5535.1 CFTR- IntronlO- - GAAAUGCCUAUUUGACAUCCAAA 23

5619 24499

CFTR- IntronlO- - UGAAAUGCCUAUUUGACAUCCAAA 24

5620 24500

CFTR- IntronlO- - GACAAACAGAAAAAGAAA 18

5621 24501

CFTR- IntronlO- - AGACAAACAGAAAAAGAAA 19

5622 24502

CFTR- IntronlO- - AAGACAAACAGAAAAAGAAA 20

5623 24503

CFTR- IntronlO- - UAAGACAAACAGAAAAAGAAA 21

5624 24504

CFTR- IntronlO- - CUAAGACAAACAGAAAAAGAAA 22

5625 24505

CFTR- IntronlO- - UCUAAGACAAACAGAAAAAGAAA 23

5626 24506

CFTR- IntronlO- - AUCUAAGACAAACAGAAAAAGAAA 24

5627 24507

CFTR- IntronlO- - AUCUAAGACAAACAGAAA 18

5628 24508

CFTR- IntronlO- - AAUCUAAGACAAACAGAAA 19

5629 24509

CFTR- IntronlO- - UAAUCUAAGACAAACAGAAA 20

5630 24510

CFTR- IntronlO- - AUAAUCUAAGACAAACAGAAA 21

5631 24511

CFTR- IntronlO- - AAUAAUCUAAGACAAACAGAAA 22

5632 24512

987

5535.1 CFTR- IntronlO- - GAAUAAUCUAAGACAAACAGAAA 23

5633 24513

CFTR- IntronlO- - CGAAUAAUCUAAGACAAACAGAAA 24

5634 24514

CFTR- IntronlO- - GGCACCAUUCACAGUAAA 18

5635 24515

CFTR- IntronlO- - UGGCACCAUUCACAGUAAA 19

5636 24516

CFTR- IntronlO- - CUGGCACCAUUCACAGUAAA 20

5637 24517

CFTR- IntronlO- - CCUGGCACCAUUCACAGUAAA 21

5638 24518

CFTR- IntronlO- - ACCUGGCACCAUUCACAGUAAA 22

5639 24519

CFTR- IntronlO- - UACCUGGCACCAUUCACAGUAAA 23

5640 24520

CFTR- IntronlO- - CUACCUGGCACCAUUCACAGUAAA 24

5641 24521

CFTR- IntronlO- - CCACUGGAGAGUUUUAAA 18

5642 24522

CFTR- IntronlO- - GCCACUGGAGAGUUUUAAA 19

5643 24523

CFTR- IntronlO- - GGCCACUGGAGAGUUUUAAA 20

5644 24524

CFTR- IntronlO- - AGGCCACUGGAGAGUUUUAAA 21

5645 24525

CFTR- IntronlO- - GAGGCCACUGGAGAGUUUUAAA 22

5646 24526

988

5535.1 CFTR- IntronlO- - AGAGGCCACUGGAGAGUUUUAAA 23

5647 24527

CFTR- IntronlO- - UAGAGGCCACUGGAGAGUUUUAAA 24

5648 24528

CFTR- IntronlO- - UACAAAAAACACAAACAA 18

5649 24529

CFTR- IntronlO- - CUACAAAAAACACAAACAA 19

5650 24530

CFTR- IntronlO- - UCUACAAAAAACACAAACAA 20

5651 24531

CFTR- IntronlO- - CUCUACAAAAAACACAAACAA 21

5652 24532

CFTR- IntronlO- - CCUCUACAAAAAACACAAACAA 22

5653 24533

CFTR- IntronlO- - ACCUCUACAAAAAACACAAACAA 23

5654 24534

CFTR- IntronlO- - CACCUCUACAAAAAACACAAACAA 24

5655 24535

CFTR- IntronlO- - UAAAGACUGUUGUAACAA 18

5656 24536

CFTR- IntronlO- - AUAAAGACUGUUGUAACAA 19

5657 24537

CFTR- IntronlO- - UAUAAAGACUGUUGUAACAA 20

5658 24538

CFTR- IntronlO- - GU AUAAAGACUGUUGUAACAA 21

5659 24539

CFTR- IntronlO- - AGUAUAAAGACUGUUGUAACAA 22

5660 24540

989

5535.1 CFTR- IntronlO- - CAGUAUAAAGACUGUUGUAACAA 23

5661 24541

CFTR- IntronlO- - CCAGUAUAAAGACUGUUGUAACAA 24

5662 24542

CFTR- IntronlO- - UAUUCUGUAGGGAGACAA 18

5663 24543

CFTR- IntronlO- - CUAUUCUGUAGGGAGACAA 19

5664 24544

CFTR-

- GCUAUUCUGUAGGGAGACAA 20

lntronlO-66 18952

CFTR- IntronlO- - GGCUAUUCUGUAGGGAGACAA 21

5665 24545

CFTR- IntronlO- - AGGCUAUUCUGUAGGGAGACAA 22

5666 24546

CFTR- IntronlO- - UAGGCUAUUCUGUAGGGAGACAA 23

5667 24547

CFTR- IntronlO- - UUAGGCUAUUCUGUAGGGAGACAA 24

5668 24548

CFTR- IntronlO- - AUAGAUGGGUUAAGCCAA 18

5669 24549

CFTR- IntronlO- - AAUAGAUGGGUUAAGCCAA 19

5670 24550

CFTR- IntronlO- - UAAUAGAUGGGUUAAGCCAA 20

5671 24551

CFTR- IntronlO- - UUAAUAGAUGGGUUAAGCCAA 21

5672 24552

CFTR- IntronlO- - CUUAAUAGAUGGGUUAAGCCAA 22

5673 24553

CFTR-

- UCUUAAUAGAUGGGUUAAGCCAA 23

IntronlO- 24554

990

5535.1 5674

CFTR- IntronlO- - CUCUUAAUAGAUGGGUUAAGCCAA 24

5675 24555

CFTR- IntronlO- - AG AAAG AAAAAACAG CAA 18

5676 24556

CFTR- IntronlO- - UAGAAAGAAAAAACAGCAA 19

5677 24557

CFTR- IntronlO- - U U AG AAAG AAAAAACAG CAA 20

5678 24558

CFTR- IntronlO- - AU UAGAAAGAAAAAACAGCAA 21

5679 24559

CFTR- IntronlO- - GAU UAGAAAGAAAAAACAGCAA 22

5680 24560

CFTR- IntronlO- - AGAUUAGAAAGAAAAAACAGCAA 23

5681 24561

CFTR- IntronlO- - UAGAUUAGAAAGAAAAAACAGCAA 24

5682 24562

CFTR- IntronlO- - ACUGUUGUAACAAAAGAA 18

5683 24563

CFTR- IntronlO- - GACUGUUGUAACAAAAGAA 19

5684 24564

CFTR- IntronlO- - AGACUGUUGUAACAAAAGAA 20

5685 24565

CFTR- IntronlO- - AAGACUGUUGUAACAAAAGAA 21

5686 24566

CFTR- IntronlO- - AAAG AC U G U U G UAACAAAAGAA 22

5687 24567

CFTR-

- UAAAGACUGUUGUAACAAAAGAA 23

IntronlO- 24568

991

5535.1 5688

CFTR- IntronlO- - A U AAAG AC U G U U G U AAC AAAAG AA 24

5689 24569

CFTR- IntronlO- - GAAGGAAAUGAGGAAGAA 18

5690 24570

CFTR- IntronlO- - AGAAGGAAAUGAGGAAGAA 19

5691 24571

CFTR- IntronlO- - AAGAAGGAAAUGAGGAAGAA 20

1105 19990

CFTR- IntronlO- - AAAGAAGGAAAUGAGGAAGAA 21

5692 24572

CFTR- IntronlO- - GAAAGAAGGAAAUGAGGAAGAA 22

5693 24573

CFTR- IntronlO- - AGAAAGAAGGAAAUGAGGAAGAA 23

5694 24574

CFTR- IntronlO- - AAGAAAGAAGGAAAUGAGGAAGAA 24

5695 24575

CFTR- IntronlO- - AAAGAGGGUUGAUAAGAA 18

5696 24576

CFTR- IntronlO- - GAAAGAGGGUUGAUAAGAA 19

5697 24577

CFTR- IntronlO- - GGAAAGAGGGUUGAUAAGAA 20

5698 24578

CFTR- IntronlO- - AGGAAAGAGGGUUGAUAAGAA 21

5699 24579

CFTR- IntronlO- - AAGGAAAGAGGGUUGAUAAGAA 22

5700 24580

CFTR-

- AAAGGAAAGAGGGUUGAUAAGAA 23

IntronlO- 24581

992

5535.1 5701

CFTR- IntronlO- - UAAAGGAAAGAGGGUUGAUAAGAA 24

5702 24582

CFTR- IntronlO- - AUCACCUGAGCCUGAGAA 18

5703 24583

CFTR- IntronlO- - GAUCACCUGAGCCUGAGAA 19

5704 24584

CFTR- IntronlO- - GGAUCACCUGAGCCUGAGAA 20

5705 24585

CFTR- IntronlO- - AGGAUCACCUGAGCCUGAGAA 21

5706 24586

CFTR- IntronlO- - GAGGAUCACCUGAGCCUGAGAA 22

5707 24587

CFTR- IntronlO- - GGAGGAUCACCUGAGCCUGAGAA 23

5708 24588

CFTR- IntronlO- - GGGAGGAUCACCUGAGCCUGAGAA 24

5709 24589

CFTR- IntronlO- - UUUAAACACUUCUGAGAA 18

5710 24590

CFTR- IntronlO- - AUUUAAACACUUCUGAGAA 19

5711 24591

CFTR- IntronlO- - UAUUUAAACACUUCUGAGAA 20

5712 24592

CFTR- IntronlO- - AUAUUUAAACACUUCUGAGAA 21

5713 24593

CFTR- IntronlO- - AAUAUUUAAACACUUCUGAGAA 22

5714 24594

CFTR-

- GAAUAUUUAAACACUUCUGAGAA 23

IntronlO- 24595

993

5535.1 5715

CFTR- IntronlO- - GGAAUAUUUAAACACUUCUGAGAA 24

5716 24596

CFTR- IntronlO- - AAGGAAUUUUAUAUAGAA 18

5717 24597

CFTR- IntronlO- - AAAGG AAU UUUAUAUAGAA 19

5718 24598

CFTR- IntronlO- - CAAAGGAAUUUUAUAUAGAA 20

5719 24599

CFTR- IntronlO- - ACAAAGG AAU UUUAUAUAGAA 21

5720 24600

CFTR- IntronlO- - U ACAAAGG AAU UUUAUAUAGAA 22

5721 24601

CFTR- IntronlO- - G U ACAAAGG AAU U U U AU AU AG AA 23

5722 24602

CFTR- IntronlO- - UGUACAAAGGAAUUUUAUAUAGAA 24

5723 24603

CFTR- IntronlO- - AAGUCUAGUUUCAAGGAA 18

5724 24604

CFTR- IntronlO- - CAAG U C U AG U U U CAAG G AA 19

5725 24605

CFTR- IntronlO- - ACAAGUCUAGUUUCAAGGAA 20

5726 24606

CFTR- IntronlO- - UACAAG U CU AG U U U CAAGG AA 21

5727 24607

CFTR- IntronlO- - GUACAAGUCUAGUUUCAAGGAA 22

5728 24608

CFTR-

- UGUACAAGUCUAGUUUCAAGGAA 23

IntronlO- 24609

994

5535.1 5729

CFTR- IntronlO- - AUG U ACAAG U CU AG U U U CAAGG AA 24

5730 24610

CFTR- IntronlO- - GAAGGAAGAAAGAAGGAA 18

5731 24611

CFTR- IntronlO- - GGAAGGAAGAAAGAAGGAA 19

5732 24612

CFTR- IntronlO- - AGGAAGGAAGAAAGAAGGAA 20

5733 24613

CFTR- IntronlO- - GAGGAAGGAAGAAAGAAGGAA 21

5734 24614

CFTR- IntronlO- - AGAGGAAGGAAGAAAGAAGGAA 22

5735 24615

CFTR- IntronlO- - GAGAGGAAGGAAGAAAGAAGGAA 23

5736 24616

CFTR- IntronlO- - AGAGAGGAAGGAAGAAAGAAGGAA 24

5737 24617

CFTR- IntronlO- - UUUUAGUAGUAUUAGGAA 18

5738 24618

CFTR- IntronlO- - CUUUUAGUAGUAUUAGGAA 19

5739 24619

CFTR-

- CCUUUUAGUAGUAUUAGGAA 20

lntronlO-350 19236

CFTR- IntronlO- - GCCUUUUAGUAGUAUUAGGAA 21

5740 24620

CFTR- IntronlO- - UGCCUUUUAGUAGUAUUAGGAA 22

5741 24621

CFTR- IntronlO- - CUGCCUUUUAGUAGUAUUAGGAA 23

5742 24622

995

5535.1 CFTR- IntronlO- - GCUGCCUUUUAGUAGUAUUAGGAA 24

5743 24623

CFTR- IntronlO- - U G AAA U U AG A A AG A A U A A 18

5744 24624

CFTR- IntronlO- - AUGAAAUUAGAAAGAAUAA 19

5745 24625

CFTR- IntronlO- - AAUGAAAUUAGAAAGAAUAA 20

5746 24626

CFTR- IntronlO- - GAAUGAAAUUAGAAAGAAUAA 21

5747 24627

CFTR- IntronlO- - AGAAUGAAAUUAGAAAGAAUAA 22

5748 24628

CFTR- IntronlO- - CAGAAUGAAAUUAGAAAGAAUAA 23

5749 24629

CFTR- IntronlO- - CCAGAAUGAAAUUAGAAAGAAUAA 24

5750 24630

CFTR- IntronlO- - AAAUAUAAGAUUGAAUAA 18

5751 24631

CFTR- IntronlO- - AAAAUAUAAGAUUGAAUAA 19

5752 24632

CFTR- IntronlO- - UAAAAUAUAAGAUUGAAUAA 20

5753 24633

CFTR- IntronlO- - CU AAAAUAUAAGAUUGAAUAA 21

5754 24634

CFTR- IntronlO- - GCUAAAAUAUAAGAUUGAAUAA 22

5755 24635

CFTR- IntronlO- - AGCUAAAAUAUAAGAUUGAAUAA 23

5756 24636

996

5535.1 CFTR- IntronlO- - UAGCUAAAAUAUAAGAUUGAAUAA 24

5757 24637

CFTR- IntronlO- - CCCAUAAAUGUUGAAUAA 18

5758 24638

CFTR- IntronlO- - CCCCAUAAAUGUUGAAUAA 19

5759 24639

CFTR- IntronlO- - GCCCCAUAAAUGUUGAAUAA 20

5760 24640

CFTR- IntronlO- - AGCCCCAUAAAUGUUGAAUAA 21

5761 24641

CFTR- IntronlO- - GAGCCCCAUAAAUGUUGAAUAA 22

5762 24642

CFTR- IntronlO- - GGAGCCCCAUAAAUGUUGAAUAA 23

5763 24643

CFTR- IntronlO- - GGGAGCCCCAUAAAUGUUGAAUAA 24

5764 24644

CFTR- IntronlO- - AGCUUAUUCUUGUAAUAA 18

5765 24645

CFTR- IntronlO- - UAGCUUAUUCUUGUAAUAA 19

5766 24646

CFTR- IntronlO- - UUAGCUUAUUCUUGUAAUAA 20

5767 24647

CFTR- IntronlO- - UUUAGCUUAUUCUUGUAAUAA 21

5768 24648

CFTR- IntronlO- - UUUUAGCUUAUUCUUGUAAUAA 22

5769 24649

CFTR- IntronlO- - GUUUUAGCUUAUUCUUGUAAUAA 23

5770 24650

997

5535.1 CFTR- IntronlO- - AGUUUUAGCUUAUUCUUGUAAUAA 24

5771 24651

CFTR- IntronlO- - CGUUUACUAGAAAGAUAA 18

5772 24652

CFTR- IntronlO- - CCGUUUACUAGAAAGAUAA 19

5773 24653

CFTR-

- GCCGUUUACUAGAAAGAUAA 20

lntronlO-69 18955

CFTR- IntronlO- - UGCCGUUUACUAGAAAGAUAA 21

5774 24654

CFTR- IntronlO- - G UG CCG U U U ACU AG AAAG AU AA 22

5775 24655

CFTR- IntronlO- - UGUGCCGUUUACUAGAAAGAUAA 23

5776 24656

CFTR- IntronlO- - AUGUGCCGUUUACUAGAAAGAUAA 24

5777 24657

CFTR- IntronlO- - CCUGCAAUUUCGAGAUAA 18

5778 24658

CFTR- IntronlO- - GCCUGCAAUUUCGAGAUAA 19

5779 24659

CFTR- IntronlO- - UGCCUGCAAUUUCGAGAUAA 20

5780 24660

CFTR- IntronlO- - UUGCCUGCAAUUUCGAGAUAA 21

5781 24661

CFTR- IntronlO- - GUUGCCUGCAAUUUCGAGAUAA 22

5782 24662

CFTR- IntronlO- - AGUUGCCUGCAAUUUCGAGAUAA 23

5783 24663

CFTR-

- CAGUUGCCUGCAAUUUCGAGAUAA 24

IntronlO- 24664

998

5535.1 5784

CFTR- IntronlO- - AGAUUAGUGUCUUUAUAA 18

5785 24665

CFTR- IntronlO- - GAGAUUAGUGUCUUUAUAA 19

5786 24666

CFTR- IntronlO- - UGAGAUUAGUGUCUUUAUAA 20

5787 24667

CFTR- IntronlO- - AUGAGAUUAGUGUCUUUAUAA 21

5788 24668

CFTR- IntronlO- - AAUGAGAUUAGUGUCUUUAUAA 22

5789 24669

CFTR- IntronlO- - AAAUGAGAUUAGUGUCUUUAUAA 23

5790 24670

CFTR- IntronlO- - UAAAUGAGAUUAGUGUCUUUAUAA 24

5791 24671

CFTR- IntronlO- - UGACCUAAGAUAUCCUAA 18

5792 24672

CFTR- IntronlO- - UUGACCUAAGAUAUCCUAA 19

5793 24673

CFTR-

- UUUGACCUAAGAUAUCCUAA 20

lntronlO-358 19244

CFTR- IntronlO- - CUUUGACCUAAGAUAUCCUAA 21

5794 24674

CFTR- IntronlO- - UCUUUGACCUAAGAUAUCCUAA 22

5795 24675

CFTR- IntronlO- - CUCUUUGACCUAAGAUAUCCUAA 23

5796 24676

CFTR- IntronlO- - CCUCUUUGACCUAAGAUAUCCUAA 24

5797 24677

999

5535.1 CFTR- IntronlO- - GGCUGGAUAAGAUUCUAA 18

5798 24678

CFTR- IntronlO- - GGGCUGGAUAAGAUUCUAA 19

5799 24679

CFTR-

- GGGGCUGGAUAAGAUUCUAA 20

Intronl0-71 18957

CFTR- IntronlO- - UGGGGCUGGAUAAGAUUCUAA 21

5800 24680

CFTR- IntronlO- - AUGGGGCUGGAUAAGAUUCUAA 22

5801 24681

CFTR- IntronlO- - GAUGGGGCUGGAUAAGAUUCUAA 23

5802 24682

CFTR- IntronlO- - AGAUGGGGCUGGAUAAGAUUCUAA 24

5803 24683

CFTR- IntronlO- - AG U U U U AAACAG AAG U AA 18

5804 24684

CFTR- IntronlO- - G AG U U U U AAACAG AAG U AA 19

5805 24685

CFTR- IntronlO- - AG AG U U U U AAACAG AAG U AA 20

5806 24686

CFTR- IntronlO- - G AG AG U U U U AAACAG AAG U AA 21

5807 24687

CFTR- IntronlO- - GG AG AG U U U U AAACAG AAG U AA 22

5808 24688

CFTR- IntronlO- - UGG AG AG U U U U AAACAG AAG U AA 23

5809 24689

CFTR- IntronlO- - CUGG AG AG U U U U AAACAG AAG U AA 24

5810 24690

CFTR-

- A AAG AAG G AAG G AAG U AA 18

IntronlO- 24691

1000

5535.1 5811

CFTR- IntronlO- - G A AAG AAG G AAG G AAG U AA 19

5812 24692

CFTR- IntronlO- - G G A A AG A AG G A AG G A AG U AA 20

5813 24693

CFTR- IntronlO- - AGGAAAGAAGGAAGGAAGUAA 21

5814 24694

CFTR- IntronlO- - A AG G A A AG A AG G AAG G AAG U A A 22

5815 24695

CFTR- IntronlO- - GAAGGAAAGAAGGAAGGAAGUAA 23

5816 24696

CFTR- IntronlO- - GGAAGGAAAGAAGGAAGGAAGUAA 24

5817 24697

CFTR- IntronlO- - GCUUUCUGGACUGAGUAA 18

5818 24698

CFTR- IntronlO- - AGCUUUCUGGACUGAGUAA 19

5819 24699

CFTR- IntronlO- - AAGCUUUCUGGACUGAGUAA 20

5820 24700

CFTR- IntronlO- - CAAGCUUUCUGGACUGAGUAA 21

5821 24701

CFTR- IntronlO- - CCAAGCUUUCUGGACUGAGUAA 22

5822 24702

CFTR- IntronlO- - UCCAAGCUUUCUGGACUGAGUAA 23

5823 24703

CFTR- IntronlO- - UUCCAAGCUUUCUGGACUGAGUAA 24

5824 24704

CFTR-

- GGGUGAAGUCUUUAGUAA 18

IntronlO- 24705

1001

5535.1 5825

CFTR- IntronlO- - AGGGUGAAGUCUUUAGUAA 19

5826 24706

CFTR- IntronlO- - GAGGGUGAAGUCUUUAGUAA 20

5827 24707

CFTR- IntronlO- - UGAGGGUGAAGUCUUUAGUAA 21

5828 24708

CFTR- IntronlO- - AUGAGGGUGAAGUCUUUAGUAA 22

5829 24709

CFTR- IntronlO- - CAUGAGGGUGAAGUCUUUAGUAA 23

5830 24710

CFTR- IntronlO- - CCAUGAGGGUGAAGUCUUUAGUAA 24

5831 24711

CFTR- IntronlO- - AUAAGUGGCCUUUAAACA 18

5832 24712

CFTR- IntronlO- - UAUAAGUGGCCUUUAAACA 19

5833 24713

CFTR- IntronlO- - AUAUAAGUGGCCUUUAAACA 20

5834 24714

CFTR- IntronlO- - AAUAUAAGUGGCCUUU AAACA 21

5835 24715

CFTR- IntronlO- - AAAUAUAAGUGGCCUUUAAACA 22

5836 24716

CFTR- IntronlO- - AAAAUAUAAGUGGCCUUUAAACA 23

5837 24717

CFTR- IntronlO- - AAAAAU AU AAG UGG CCU U U AAACA 24

5838 24718

CFTR-

- ACCAUCCUGGCUAACACA 18

IntronlO- 24719

1002

5535.1 5839

CFTR- IntronlO- - GACCAUCCUGGCUAACACA 19

5840 24720

CFTR- IntronlO- - AGACCAUCCUGGCUAACACA 20

5841 24721

CFTR- IntronlO- - AAGACCAUCCUGGCUAACACA 21

5842 24722

CFTR- IntronlO- - CAAGACCAUCCUGGCUAACACA 22

5843 24723

CFTR- IntronlO- - UCAAGACCAUCCUGGCUAACACA 23

5844 24724

CFTR- IntronlO- - AUCAAGACCAUCCUGGCUAACACA 24

5845 24725

CFTR- IntronlO- - CAAUAUUUUGUUAACACA 18

5846 24726

CFTR- IntronlO- - CCAAU AU U U UG U U AACACA 19

5847 24727

CFTR- IntronlO- - U CCAAU AU U U UG U U AACACA 20

5848 24728

CFTR- IntronlO- - U U CCAAU AU U U UG U U AACACA 21

5849 24729

CFTR- IntronlO- - U U U CCAAU AU U U UG U U AACACA 22

5850 24730

CFTR- IntronlO- - GUUUCCAAUAUUUUGUUAACACA 23

5851 24731

CFTR- IntronlO- - UGUUUCCAAUAUUUUGUUAACACA 24

5852 24732

CFTR-

- UUCCAUAUUCAAAGCACA 18

IntronlO- 24733

1003

5535.1 5853

CFTR- IntronlO- - UUUCCAUAUUCAAAGCACA 19

5854 24734

CFTR- IntronlO- - CUUUCCAUAUUCAAAGCACA 20

5855 24735

CFTR- IntronlO- - ACUUUCCAUAUUCAAAGCACA 21

5856 24736

CFTR- IntronlO- - AACU UUCCAUAUU CAAAG CACA 22

5857 24737

CFTR- IntronlO- - CAACU U U CCAU AU U CAAAGCACA 23

5858 24738

CFTR- IntronlO- - ACAACUUUCCAUAUUCAAAGCACA 24

5859 24739

CFTR- IntronlO- - CAUAUGAGAAAAGUCACA 18

5860 24740

CFTR- IntronlO- - GCAUAUGAGAAAAGUCACA 19

5861 24741

CFTR- IntronlO- - GGCAUAUGAGAAAAGUCACA 20

5862 24742

CFTR- IntronlO- - UGGCAUAUGAGAAAAGUCACA 21

5863 24743

CFTR- IntronlO- - AUGGCAUAUGAGAAAAGUCACA 22

5864 24744

CFTR- IntronlO- - AAUGGCAUAUGAGAAAAGUCACA 23

5865 24745

CFTR- IntronlO- - CAAUGGCAUAUGAGAAAAGUCACA 24

5866 24746

CFTR-

- CUGGCAUAGAGUAAGACA 18

IntronlO- 24747

1004

5535.1 5867

CFTR- IntronlO- - GCUGGCAUAGAGUAAGACA 19

5868 24748

CFTR-

- GGCUGGCAUAGAGUAAGACA 20

lntronlO-74 18960

CFTR- IntronlO- - AGGCUGGCAUAGAGUAAGACA 21

5869 24749

CFTR- IntronlO- - GAGGCUGGCAUAGAGUAAGACA 22

5870 24750

CFTR- IntronlO- - UGAGGCUGGCAUAGAGUAAGACA 23

5871 24751

CFTR- IntronlO- - CUGAGGCUGGCAUAGAGUAAGACA 24

5872 24752

CFTR- IntronlO- - CUAUUCUGUAGGGAGACA 18

5873 24753

CFTR- IntronlO- - GCUAUUCUGUAGGGAGACA 19

5874 24754

CFTR-

- GGCUAUUCUGUAGGGAGACA 20

lntronlO-75 18961

CFTR- IntronlO- - AGGCUAUUCUGUAGGGAGACA 21

5875 24755

CFTR- IntronlO- - UAGGCUAUUCUGUAGGGAGACA 22

5876 24756

CFTR- IntronlO- - UUAGGCUAUUCUGUAGGGAGACA 23

5877 24757

CFTR- IntronlO- - UUUAGGCUAUUCUGUAGGGAGACA 24

5878 24758

CFTR- IntronlO- - UUUUUUUCAGUUAAUACA 18

5879 24759

1005

5535.1 CFTR- IntronlO- - UUUUUUUUCAGUUAAUACA 19

5880 24760

CFTR- IntronlO- - AUUUUUUUUCAGUUAAUACA 20

5881 24761

CFTR- IntronlO- - AAUUUUUUUUCAGUUAAUACA 21

5882 24762

CFTR- IntronlO- - GAAUUUUUUUUCAGUUAAUACA 22

5883 24763

CFTR- IntronlO- - UGAAUUUUUUUUCAGUUAAUACA 23

5884 24764

CFTR- IntronlO- - GUGAAUUUUUUUUCAGUUAAUACA 24

5885 24765

CFTR- IntronlO- - AUCAUUUCAACUUAUACA 18

5886 24766

CFTR- IntronlO- - UAUCAUUUCAACUUAUACA 19

5887 24767

CFTR- IntronlO- - AUAUCAUUUCAACUUAUACA 20

5888 24768

CFTR- IntronlO- - AAUAUCAUUUCAACUUAUACA 21

5889 24769

CFTR- IntronlO- - AAAUAUCAUUUCAACUUAUACA 22

5890 24770

CFTR- IntronlO- - AAAAUAUCAUUUCAACUUAUACA 23

5891 24771

CFTR- IntronlO- - U AAAAU AU CAU U U CAACU U AU ACA 24

5892 24772

CFTR- IntronlO- - UAGGUUUAAUUUUGUACA 18

5893 24773

1006

5535.1 CFTR- IntronlO- - CUAGGUUUAAUUUUGUACA 19

5894 24774

CFTR- IntronlO- - UCUAGGUUUAAUUUUGUACA 20

5895 24775

CFTR- IntronlO- - UUCUAGGUUUAAUUUUGUACA 21

5896 24776

CFTR- IntronlO- - CUUCUAGGUUUAAUUUUGUACA 22

5897 24777

CFTR- IntronlO- - ACUUCUAGGUUUAAUUUUGUACA 23

5898 24778

CFTR- IntronlO- - CACUUCUAGGUUUAAUUUUGUACA 24

5899 24779

CFTR- IntronlO- - GGGUGAGAUUAGAGGCCA 18

5900 24780

CFTR- IntronlO- - UGGGUGAGAUUAGAGGCCA 19

5901 24781

CFTR- IntronlO- - CUGGGUGAGAUUAGAGGCCA 20

5902 24782

CFTR- IntronlO- - UCUGGGUGAGAUUAGAGGCCA 21

5903 24783

CFTR- IntronlO- - CUCUGGGUGAGAUUAGAGGCCA 22

5904 24784

CFTR- IntronlO- - UCUCUGGGUGAGAUUAGAGGCCA 23

5905 24785

CFTR- IntronlO- - UUCUCUGGGUGAGAUUAGAGGCCA 24

5906 24786

CFTR- IntronlO- - CUUUCCAUAUUCAAAGCA 18

5907 24787

1007

5535.1 CFTR- IntronlO- - ACUUUCCAUAUUCAAAGCA 19

5908 24788

CFTR- IntronlO- - AACUUUCCAUAUUCAAAGCA 20

5909 24789

CFTR- IntronlO- - CAACU UUCCAUAUU CAAAGCA 21

5910 24790

CFTR- IntronlO- - ACAACUUUCCAUAUUCAAAGCA 22

5911 24791

CFTR- IntronlO- - G ACAACU UUCCAUAUU CAAAGCA 23

5912 24792

CFTR- IntronlO- - GG ACAACU U U CCAU AU U CAAAG CA 24

5913 24793

CFTR- IntronlO- - GAGACAAGGGAGGAAGCA 18

5914 24794

CFTR- IntronlO- - GGAGACAAGGGAGGAAGCA 19

5915 24795

CFTR-

- GGGAGACAAGGGAGGAAGCA 20

lntronlO-650 19536

CFTR- IntronlO- - AGGGAGACAAGGGAGGAAGCA 21

5916 24796

CFTR- IntronlO- - UAGGGAGACAAGGGAGGAAGCA 22

5917 24797

CFTR- IntronlO- - GUAGGGAGACAAGGGAGGAAGCA 23

5918 24798

CFTR- IntronlO- - UGUAGGGAGACAAGGGAGGAAGCA 24

5919 24799

CFTR- IntronlO- - GAUUCUGUUUAAAUAGCA 18

5920 24800

CFTR-

- UGAUUCUGUUUAAAUAGCA 19

IntronlO- 24801

1008

5535.1 5921

CFTR- IntronlO- - CUGAUUCUGUUUAAAUAGCA 20

5922 24802

CFTR- IntronlO- - CCUGAUUCUGUUUAAAUAGCA 21

5923 24803

CFTR- IntronlO- - CCCUGAUUCUGUUUAAAUAGCA 22

5924 24804

CFTR- IntronlO- - CCCCUGAUUCUGUUUAAAUAGCA 23

5925 24805

CFTR- IntronlO- - UCCCCUGAUUCUGUUUAAAUAGCA 24

5926 24806

CFTR- IntronlO- - AGUGCCACUAGUGAUGCA 18

5927 24807

CFTR- IntronlO- - AAGUGCCACUAGUGAUGCA 19

5928 24808

CFTR- IntronlO- - AAAGUGCCACUAGUGAUGCA 20

1129 20014

CFTR- IntronlO- - CAAAGUGCCACUAGUGAUGCA 21

5929 24809

CFTR- IntronlO- - ACAAAGUGCCACUAGUGAUGCA 22

5930 24810

CFTR- IntronlO- - UACAAAGUGCCACUAGUGAUGCA 23

5931 24811

CFTR- IntronlO- - AUACAAAGUGCCACUAGUGAUGCA 24

5932 24812

CFTR- IntronlO- - UGAGAAGUGGAGGCUGCA 18

5933 24813

CFTR-

- CUGAGAAGUGGAGGCUGCA 19

IntronlO- 24814

1009

5535.1 5934

CFTR- IntronlO- - CCUGAGAAGUGGAGGCUGCA 20

5935 24815

CFTR- IntronlO- - GCCUGAGAAGUGGAGGCUGCA 21

5936 24816

CFTR- IntronlO- - AGCCUGAGAAGUGGAGGCUGCA 22

5937 24817

CFTR- IntronlO- - GAGCCUGAGAAGUGGAGGCUGCA 23

5938 24818

CFTR- IntronlO- - UGAGCCUGAGAAGUGGAGGCUGCA 24

5939 24819

CFTR- IntronlO- - CAGGAGGCAGAACUUGCA 18

5940 24820

CFTR- IntronlO- - CCAGGAGGCAGAACUUGCA 19

5941 24821

CFTR- IntronlO- - CCCAGGAGGCAGAACUUGCA 20

5942 24822

CFTR- IntronlO- - ACCCAGGAGGCAGAACUUGCA 21

5943 24823

CFTR- IntronlO- - AACCCAGGAGGCAGAACUUGCA 22

5944 24824

CFTR- IntronlO- - GAACCCAGGAGGCAGAACUUGCA 23

5945 24825

CFTR- IntronlO- - UGAACCCAGGAGGCAGAACUUGCA 24

5946 24826

CFTR- IntronlO- - GGCAUAUGAGAAAAGUCA 18

5947 24827

CFTR-

- UGGCAUAUGAGAAAAGUCA 19

IntronlO- 24828

1010

5535.1 5948

CFTR- IntronlO- - AUGGCAUAUGAGAAAAGUCA 20

5949 24829

CFTR- IntronlO- - AAUGGCAUAUGAGAAAAGUCA 21

5950 24830

CFTR- IntronlO- - CAAUGGCAUAUGAGAAAAGUCA 22

5951 24831

CFTR- IntronlO- - ACAAUGGCAUAUGAGAAAAGUCA 23

5952 24832

CFTR- IntronlO- - AACAAUGGCAUAUGAGAAAAGUCA 24

5953 24833

CFTR- IntronlO- - AG AACAG U AAGG AGG U CA 18

5954 24834

CFTR- IntronlO- - AAG AACAG U AAGG AGG U CA 19

5955 24835

CFTR- IntronlO- - GAAGAACAGUAAGGAGGUCA 20

5956 24836

CFTR- IntronlO- - UGAAGAACAGUAAGGAGGUCA 21

5957 24837

CFTR- IntronlO- - UUGAAGAACAGUAAGGAGGUCA 22

5958 24838

CFTR- IntronlO- - U U U G AAG AACAG U AAG GAG G U C A 23

5959 24839

CFTR- IntronlO- - G U U UG AAG AACAG U AAGG AGG U CA 24

5960 24840

CFTR- IntronlO- - GAGGGUAGAAUACUGUCA 18

5961 24841

CFTR-

- GGAGGGUAGAAUACUGUCA 19

IntronlO- 24842

1011

5535.1 5962

CFTR- IntronlO- - GGGAGGGUAGAAUACUGUCA 20

5963 24843

CFTR- IntronlO- - AGGGAGGGUAGAAUACUGUCA 21

5964 24844

CFTR- IntronlO- - CAGGGAGGGUAGAAUACUGUCA 22

5965 24845

CFTR- IntronlO- - ACAGGGAGGGUAGAAUACUGUCA 23

5966 24846

CFTR- IntronlO- - GACAGGGAGGGUAGAAUACUGUCA 24

5967 24847

CFTR- IntronlO- - UGUACAAGUCUAGUUUCA 18

5968 24848

CFTR- IntronlO- - AUGUACAAGUCUAGUUUCA 19

5969 24849

CFTR-

- GAUGUACAAGUCUAGUUUCA 20

lntronlO-79 18965

CFTR- IntronlO- - GGAUGUACAAGUCUAGUUUCA 21

5970 24850

CFTR- IntronlO- - UGGAUGUACAAGUCUAGUUUCA 22

5971 24851

CFTR- IntronlO- - UUGGAUGUACAAGUCUAGUUUCA 23

5972 24852

CFTR- IntronlO- - GUUGGAUGUACAAGUCUAGUUUCA 24

5973 24853

CFTR- IntronlO- - AAGACAAACAGAAAAAGA 18

5974 24854

CFTR- IntronlO- - UAAGACAAACAGAAAAAGA 19

5975 24855

1012

5535.1 CFTR- IntronlO- - CUAAGACAAACAGAAAAAGA 20

5976 24856

CFTR- IntronlO- - UCUAAGACAAACAGAAAAAGA 21

5977 24857

CFTR- IntronlO- - AUCUAAGACAAACAGAAAAAGA 22

5978 24858

CFTR- IntronlO- - AAUCUAAGACAAACAGAAAAAGA 23

5979 24859

CFTR- IntronlO- - UAAUCUAAGACAAACAGAAAAAGA 24

5980 24860

CFTR- IntronlO- - CAAACAGAAAAAGAAAGA 18

5981 24861

CFTR- IntronlO- - ACAAACAGAAAAAGAAAGA 19

5982 24862

CFTR- IntronlO- - GACAAACAGAAAAAGAAAGA 20

5983 24863

CFTR- IntronlO- - AGACAAACAGAAAAAGAAAGA 21

5984 24864

CFTR- IntronlO- - AAGACAAACAGAAAAAGAAAGA 22

5985 24865

CFTR- IntronlO- - UAAGACAAACAGAAAAAGAAAGA 23

5986 24866

CFTR- IntronlO- - CUAAGACAAACAGAAAAAGAAAGA 24

5987 24867

CFTR- IntronlO- - GAGAGGAAGGAAGAAAGA 18

5988 24868

CFTR- IntronlO- - AGAGAGGAAGGAAGAAAGA 19

5989 24869

1013

5535.1 CFTR- IntronlO- - AAGAGAGGAAGGAAGAAAGA 20

1137 20022

CFTR- IntronlO- - AAAGAGAGGAAGGAAGAAAGA 21

5990 24870

CFTR- IntronlO- - GAAAGAGAGGAAGGAAGAAAGA 22

5991 24871

CFTR- IntronlO- - AGAAAGAGAGGAAGGAAGAAAGA 23

5992 24872

CFTR- IntronlO- - AAGAAAGAGAGGAAGGAAGAAAGA 24

5993 24873

CFTR- IntronlO- - G AAG G AAG G AAG G AAAG A 18

5994 24874

CFTR- IntronlO- - GGAAGGAAGGAAGGAAAGA 19

5995 24875

CFTR- IntronlO- - AG G AAG G AAG G AAG G AAAG A 20

1138 20023

CFTR- IntronlO- - G AG G AAG G AAG G AAG G AAAG A 21

5996 24876

CFTR- IntronlO- - GGAGGAAGGAAGGAAGGAAAGA 22

5997 24877

CFTR- IntronlO- - AG GAG G AAG G AAG G AAG G AAAG A 23

5998 24878

CFTR- IntronlO- - U AG GAG G AAG G AAG G AAG G AAAG A 24

5999 24879

CFTR- IntronlO- - GUCUAGUUUCAAGGAAGA 18

6000 24880

CFTR- IntronlO- - AGUCUAGUUUCAAGGAAGA 19

6001 24881

1014

5535.1 CFTR-

- AAGUCUAGUUU C A AG G A AG A 20

lntronlO-372 19258

CFTR- IntronlO- - CAAGUCUAGUUUCAAGGAAGA 21

6002 24882

CFTR- IntronlO- - ACAAGUCUAGUUUCAAGGAAGA 22

6003 24883

CFTR- IntronlO- - UACAAGUCUAGUUUCAAGGAAGA 23

6004 24884

CFTR- IntronlO- - GUACAAGUCUAGUUUCAAGGAAGA 24

6005 24885

CFTR- IntronlO- - GAAAGAGAGGAAGGAAGA 18

6006 24886

CFTR- IntronlO- - AGAAAGAGAGGAAGGAAGA 19

6007 24887

CFTR- IntronlO- - AAGAAAGAGAGGAAGGAAGA 20

6008 24888

CFTR- IntronlO- - A A AG A A AG AG AGGAAGGAAGA 21

6009 24889

CFTR- IntronlO- - AAAAGAAAGAGAGGAAGGAAGA 22

6010 24890

CFTR- IntronlO- - AAAAAGAAAGAGAGGAAGGAAGA 23

6011 24891

CFTR- IntronlO- - GAAAAAGAAAGAGAGGAAGGAAGA 24

6012 24892

CFTR- IntronlO- - AGAAGGAAAUGAGGAAGA 18

6013 24893

CFTR- IntronlO- - AAGAAGGAAAUGAGGAAGA 19

6014 24894

CFTR-

- AAAGAAGGAAAUGAGGAAGA 20

IntronlO- 24895

1015

5535.1 6015

CFTR- IntronlO- - G A A AG A AG G AAA UGAGGAAGA 21

6016 24896

CFTR- IntronlO- - AGAAAGAAGGAAAUGAGGAAGA 22

6017 24897

CFTR- IntronlO- - AAGAAAGAAGGAAAUGAGGAAGA 23

6018 24898

CFTR- IntronlO- - GAAGAAAGAAGGAAAUGAGGAAGA 24

6019 24899

CFTR- IntronlO- - GGGCUGGUAGUGUGAAGA 18

6020 24900

CFTR- IntronlO- - GGGGCUGGUAGUGUGAAGA 19

6021 24901

CFTR-

- GGGGGCUGGUAGUGUGAAGA 20

Intronl0-80 18966

CFTR- IntronlO- - AGGGGGCUGGUAGUGUGAAGA 21

6022 24902

CFTR- IntronlO- - GAGGGGGCUGGUAGUGUGAAGA 22

6023 24903

CFTR- IntronlO- - AGAGGGGGCUGGUAGUGUGAAGA 23

6024 24904

CFTR- IntronlO- - AAGAGGGGGCUGGUAGUGUGAAGA 24

6025 24905

CFTR- IntronlO- - AGAAGGAAGGAAGUAAGA 18

6026 24906

CFTR- IntronlO- - A AG A AG G A AG G A AG U A AG A 19

6027 24907

CFTR- IntronlO- - AAAGAAGGAAGGAAGUAAGA 20

1139 20024

1016

5535.1 CFTR- IntronlO- - G A A AG A AG G A AG G A AG U A AG A 21

6028 24908

CFTR- IntronlO- - G G A A AG A AG G A AG G A AG UAAGA 22

6029 24909

CFTR- IntronlO- - AGGAAAGAAGGAAGGAAGUAAGA 23

6030 24910

CFTR- IntronlO- - AAGGAAAGAAGGAAGGAAGUAAGA 24

6031 24911

CFTR- IntronlO- - GGCUGGCAUAGAGUAAGA 18

6032 24912

CFTR- IntronlO- - AGGCUGGCAUAGAGUAAGA 19

6033 24913

CFTR- IntronlO- - GAGGCUGGCAUAGAGUAAGA 20

6034 24914

CFTR- IntronlO- - UGAGGCUGGCAUAGAGUAAGA 21

6035 24915

CFTR- IntronlO- - CUGAGGCUGGCAUAGAGUAAGA 22

6036 24916

CFTR- IntronlO- - ACUGAGGCUGGCAUAGAGUAAGA 23

6037 24917

CFTR- IntronlO- - CACUGAGGCUGGCAUAGAGUAAGA 24

6038 24918

CFTR- IntronlO- - UCUAGCCUGGGUGACAGA 18

6039 24919

CFTR- IntronlO- - CUCUAGCCUGGGUGACAGA 19

6040 24920

CFTR- IntronlO- - ACUCUAGCCUGGGUGACAGA 20

6041 24921

1017

5535.1 CFTR- IntronlO- - CACUCUAGCCUGGGUGACAGA 21

6042 24922

CFTR- IntronlO- - GCACUCUAGCCUGGGUGACAGA 22

6043 24923

CFTR- IntronlO- - UGCACUCUAGCCUGGGUGACAGA 23

6044 24924

CFTR- IntronlO- - CUGCACUCUAGCCUGGGUGACAGA 24

6045 24925

CFTR- IntronlO- - AGGUCAAACUUGACCAGA 18

6046 24926

CFTR- IntronlO- - AAGGUCAAACUUGACCAGA 19

6047 24927

CFTR- IntronlO- - GAAGGUCAAACUUGACCAGA 20

6048 24928

CFTR- IntronlO- - AGAAGGUCAAACUUGACCAGA 21

6049 24929

CFTR- IntronlO- - GAGAAGGUCAAACUUGACCAGA 22

6050 24930

CFTR- IntronlO- - AGAGAAGGUCAAACUUGACCAGA 23

6051 24931

CFTR- IntronlO- - UAGAGAAGGUCAAACUUGACCAGA 24

6052 24932

CFTR- IntronlO- - AAUU U AACAU U U U CCAGA 18

6053 24933

CFTR- IntronlO- - AAAU U U AACAU U U U CCAGA 19

6054 24934

CFTR- IntronlO- - AAAAU U U AACAU U U U CCAGA 20

6055 24935

1018

5535.1 CFTR- IntronlO- - G AAAAU U U AACAU U U U CCAG A 21

6056 24936

CFTR- IntronlO- - GG AAAAU U U AACAU U U U CCAG A 22

6057 24937

CFTR- IntronlO- - GGG AAAAU U U AACAU U U U CCAG A 23

6058 24938

CFTR- IntronlO- - AGGG AAAAU U U AACAU U U U CCAG A 24

6059 24939

CFTR- IntronlO- - A AG U G C A A AG C U U U C AG A 18

6060 24940

CFTR- IntronlO- - CAAG U G CAAAG C U U U C AG A 19

6061 24941

CFTR-

- GCAAGUG CAAAG CU U U C AG A 20

lntronlO-82 18968

CFTR- IntronlO- - AG CAAG U G CAAAG C U U U C AG A 21

6062 24942

CFTR- IntronlO- - AAG CAAG U G CAAAG C U U U C AG A 22

6063 24943

CFTR- IntronlO- - GAAGCAAGUGCAAAGCUUUCAGA 23

6064 24944

CFTR- IntronlO- - UGAAGCAAGUG CAAAG C U U U C AG A 24

6065 24945

CFTR- IntronlO- - AGGGUUGAUAAGAAGAGA 18

6066 24946

CFTR- IntronlO- - GAGGGUUGAUAAGAAGAGA 19

6067 24947

CFTR- IntronlO- - AGAGGGUUGAUAAGAAGAGA 20

6068 24948

CFTR-

- AAGAGGGUUGAUAAGAAGAGA 21

IntronlO- 24949

1019

5535.1 6069

CFTR- IntronlO- - AAAGAGGGUUGAUAAGAAGAGA 22

6070 24950

CFTR- IntronlO- - GAAAGAGGGUUGAUAAGAAGAGA 23

6071 24951

CFTR- IntronlO- - GGAAAGAGGGUUGAUAAGAAGAGA 24

6072 24952

CFTR- IntronlO- - AUCAAAUUAGAGAUGAGA 18

6073 24953

CFTR- IntronlO- - AAUCAAAUUAGAGAUGAGA 19

6074 24954

CFTR- IntronlO- - GAAUCAAAUUAGAGAUGAGA 20

6075 24955

CFTR- IntronlO- - AGAAUCAAAUUAGAGAUGAGA 21

6076 24956

CFTR- IntronlO- - AAGAAUCAAAUUAGAGAUGAGA 22

6077 24957

CFTR- IntronlO- - AAAGAAUCAAAUUAGAGAUGAGA 23

6078 24958

CFTR- IntronlO- - GAAAGAAUCAAAUUAGAGAUGAGA 24

6079 24959

CFTR- IntronlO- - A A A A A A UAGUAGAUUAGA 18

6080 24960

CFTR- IntronlO- - GAAAAAAUAGUAGAUUAGA 19

6081 24961

CFTR- IntronlO- - U G A A A A A A UAGUAGAUUAGA 20

6082 24962

CFTR-

- CUGAAAAAAUAGUAGAUUAGA 21

IntronlO- 24963

1020

5535.1 6083

CFTR- IntronlO- - UCUGAAAAAAUAGUAGAUUAGA 22

6084 24964

CFTR- IntronlO- - AUCUGAAAAAAUAGUAGAUUAGA 23

6085 24965

CFTR- IntronlO- - CAU CUG AAAAAAU AG U AG AU U AG A 24

6086 24966

CFTR- IntronlO- - GAGCUUUCUAGUAUUAGA 18

6087 24967

CFTR- IntronlO- - AGAGCUUUCUAGUAUUAGA 19

6088 24968

CFTR- IntronlO- - AAGAGCUUUCUAGUAUUAGA 20

6089 24969

CFTR- IntronlO- - AAAGAGCUUUCUAGUAUUAGA 21

6090 24970

CFTR- IntronlO- - GAAAGAGCUUUCUAGUAUUAGA 22

6091 24971

CFTR- IntronlO- - AGAAAGAGCUUUCUAGUAUUAGA 23

6092 24972

CFTR- IntronlO- - GAGAAAGAGCUUUCUAGUAUUAGA 24

6093 24973

CFTR- IntronlO- - GGAUAAGAUUCUAAAGGA 18

6094 24974

CFTR- IntronlO- - UGGAUAAGAUUCUAAAGGA 19

6095 24975

CFTR- IntronlO- - CUGGAUAAGAUUCUAAAGGA 20

6096 24976

CFTR-

- GCUGGAUAAGAUUCUAAAGGA 21

IntronlO- 24977

1021

5535.1 6097

CFTR- IntronlO- - GGCUGGAUAAGAUUCUAAAGGA 22

6098 24978

CFTR- IntronlO- - GGGCUGGAUAAGAUUCUAAAGGA 23

6099 24979

CFTR- IntronlO- - GGGGCUGGAUAAGAUUCUAAAGGA 24

6100 24980

CFTR- IntronlO- - GAAGGAAGGAAAGAAGGA 18

6101 24981

CFTR- IntronlO- - GGAAGGAAGGAAAGAAGGA 19

6102 24982

CFTR- IntronlO- - AGGAAGGAAGGAAAGAAGGA 20

1145 20030

CFTR- IntronlO- - AAG G AAG G AAG G AAAG AAG G A 21

6103 24983

CFTR- IntronlO- - GAAGGAAGGAAGG A A AG A AG G A 22

6104 24984

CFTR- IntronlO- - GGAAGGAAGGAAGGAAAGAAGGA 23

6105 24985

CFTR- IntronlO- - AGGAAGGAAGGAAGGAAAGAAGGA 24

6106 24986

CFTR- IntronlO- - GGAGGAAGGAAGGAAGGA 18

6107 24987

CFTR- IntronlO- - AGGAGGAAGGAAGGAAGGA 19

6108 24988

CFTR- IntronlO- - UAGGAGGAAGGAAGGAAGGA 20

6109 24989

CFTR-

- GU AGGAGGAAGGAAGGAAGGA 21

IntronlO- 24990

1022

5535.1 6110

CFTR- IntronlO- - AG U AGG AGG AAGG AAGG AAGG A 22

6111 24991

CFTR- IntronlO- - AAGUAGGAGGAAGGAAGGAAGGA 23

6112 24992

CFTR- IntronlO- - GAAGUAGGAGGAAGGAAGGAAGGA 24

6113 24993

CFTR- IntronlO- - AGUAGGAGGAAGGAAGGA 18

6114 24994

CFTR- IntronlO- - AAG U AGG AGG AAGG AAGG A 19

6115 24995

CFTR-

- GAAG U AGG AGG AAGG AAGG A 20

lntronlO-652 19538

CFTR- IntronlO- - GGAAGUAGGAGGAAGGAAGGA 21

6116 24996

CFTR- IntronlO- - AGGAAGUAGGAGGAAGGAAGGA 22

6117 24997

CFTR- IntronlO- - AAGGAAGUAGGAGGAAGGAAGGA 23

6118 24998

CFTR- IntronlO- - AAAGGAAGUAGGAGGAAGGAAGGA 24

6119 24999

CFTR- IntronlO- - AGGAAGUAGGAGGAAGGA 18

6120 25000

CFTR- IntronlO- - AAGGAAGUAGGAGGAAGGA 19

6121 25001

CFTR- IntronlO- - AAAGGAAGUAGGAGGAAGGA 20

1146 20031

CFTR- IntronlO- - GAAAGGAAGUAGGAGGAAGGA 21

6122 25002

1023

5535.1 CFTR- IntronlO- - AGAAAGGAAGUAGGAGGAAGGA 22

6123 25003

CFTR- IntronlO- - AAGAAAGGAAGUAGGAGGAAGGA 23

6124 25004

CFTR- IntronlO- - GAAGAAAGGAAGUAGGAGGAAGGA 24

6125 25005

CFTR- IntronlO- - UUAGAAAGAAUAAGAGGA 18

6126 25006

CFTR- IntronlO- - AUUAGAAAGAAUAAGAGGA 19

6127 25007

CFTR- IntronlO- - AAUUAGAAAGAAUAAGAGGA 20

6128 25008

CFTR- IntronlO- - AAAU U AG AAAG AAU AAG AGG A 21

6129 25009

CFTR- IntronlO- - GAAAUUAGAAAGAAUAAGAGGA 22

6130 25010

CFTR- IntronlO- - UGAAAUUAGAAAGAAUAAGAGGA 23

6131 25011

CFTR- IntronlO- - AUGAAAUUAGAAAGAAUAAGAGGA 24

6132 25012

CFTR- IntronlO- - AGAAAAAGAAAGAGAGGA 18

6133 25013

CFTR- IntronlO- - CAGAAAAAGAAAGAGAGGA 19

6134 25014

CFTR- IntronlO- - A C AG A A A A AG A A AG AG AG G A 20

1149 20034

CFTR- IntronlO- - AACAGAAAAAGAAAGAGAGGA 21

6135 25015

1024

5535.1 CFTR- IntronlO- - A A AC AG A A A A AG A A AG AG AG G A 22

6136 25016

CFTR- IntronlO- - CAAACAGAAAAAGAAAGAGAGGA 23

6137 25017

CFTR- IntronlO- - ACAAACAGAAAAAGAAAGAGAGGA 24

6138 25018

CFTR- IntronlO- - AGAAAGGAAGUAGGAGGA 18

6139 25019

CFTR- IntronlO- - AAGAAAGGAAGUAGGAGGA 19

6140 25020

CFTR-

- GAAGAAAGGAAGUAGGAGGA 20

lntronlO-653 19539

CFTR- IntronlO- - GGAAGAAAGGAAGUAGGAGGA 21

6141 25021

CFTR- IntronlO- - AGG AAGAAAGGAAGUAGGAGGA 22

6142 25022

CFTR- IntronlO- - GAGGAAGAAAGGAAGUAGGAGGA 23

6143 25023

CFTR- IntronlO- - UGAGGAAGAAAGGAAGUAGGAGGA 24

6144 25024

CFTR- IntronlO- - CUUUUAGUAGUAUUAGGA 18

6145 25025

CFTR- IntronlO- - CCUUUUAGUAGUAUUAGGA 19

6146 25026

CFTR- IntronlO- - GCCUUUUAGUAGUAUUAGGA 20

6147 25027

CFTR- IntronlO- - UGCCUUUUAGUAGUAUUAGGA 21

6148 25028

CFTR-

- CUGCCUUUUAGUAGUAUUAGGA 22

IntronlO- 25029

1025

5535.1 6149

CFTR- IntronlO- - GCUGCCUUUUAGUAGUAUUAGGA 23

6150 25030

CFTR- IntronlO- - GGCUGCCUUUUAGUAGUAUUAGGA 24

6151 25031

CFTR- IntronlO- - GGAGAAACAGGUUUUGGA 18

6152 25032

CFTR- IntronlO- - GGGAGAAACAGGUUUUGGA 19

6153 25033

CFTR- IntronlO- - UGGGAGAAACAGGUUUUGGA 20

1157 20042

CFTR- IntronlO- - AUGGGAGAAACAGGUUUUGGA 21

6154 25034

CFTR- IntronlO- - AAUGGGAGAAACAGGUUUUGGA 22

6155 25035

CFTR- IntronlO- - UAAUGGGAGAAACAGGUUUUGGA 23

6156 25036

CFTR- IntronlO- - AUAAUGGGAGAAACAGGUUUUGGA 24

6157 25037

CFTR- IntronlO- - AUCACUGGAUGCCCUUGA 18

6158 25038

CFTR- IntronlO- - CAUCACUGGAUGCCCUUGA 19

6159 25039

CFTR- IntronlO- - GCAUCACUGGAUGCCCUUGA 20

6160 25040

CFTR- IntronlO- - UGCAUCACUGGAUGCCCUUGA 21

6161 25041

CFTR-

- UUGCAUCACUGGAUGCCCUUGA 22

IntronlO- 25042

1026

5535.1 6162

CFTR- IntronlO- - UUUGCAUCACUGGAUGCCCUUGA 23

6163 25043

CFTR- IntronlO- - UUUUGCAUCACUGGAUGCCCUUGA 24

6164 25044

CFTR- IntronlO- - AUUCAGGACAUGCUUUGA 18

6165 25045

CFTR- IntronlO- - GAUUCAGGACAUGCUUUGA 19

6166 25046

CFTR- IntronlO- - AGAUUCAGGACAUGCUUUGA 20

1164 20049

CFTR- IntronlO- - CAGAUUCAGGACAUGCUUUGA 21

6167 25047

CFTR- IntronlO- - UCAGAUUCAGGACAUGCUUUGA 22

6168 25048

CFTR- IntronlO- - AUCAGAUUCAGGACAUGCUUUGA 23

6169 25049

CFTR- IntronlO- - GAUCAGAUUCAGGACAUGCUUUGA 24

6170 25050

CFTR- IntronlO- - CUGUCUAGCCUAGAAAUA 18

6171 25051

CFTR- IntronlO- - ACUGUCUAGCCUAGAAAUA 19

6172 25052

CFTR- IntronlO- - AACUGUCUAGCCUAGAAAUA 20

6173 25053

CFTR- IntronlO- - AAACUGUCUAGCCUAGAAAUA 21

6174 25054

CFTR-

- CAAACUGUCUAGCCUAGAAAUA 22

IntronlO- 25055

1027

5535.1 6175

CFTR- IntronlO- - ACAAACUGUCUAGCCUAGAAAUA 23

6176 25056

CFTR- IntronlO- - CACAAACUGUCUAGCCUAGAAAUA 24

6177 25057

CFTR- IntronlO- - CCGGUGUCUUCUGAAAUA 18

6178 25058

CFTR- IntronlO- - ACCGGUGUCUUCUGAAAUA 19

6179 25059

CFTR-

- AACCGGUGUCUUCUGAAAUA 20

lntronlO-380 19266

CFTR- IntronlO- - UAACCGGUGUCUUCUGAAAUA 21

6180 25060

CFTR- IntronlO- - UUAACCGGUGUCUUCUGAAAUA 22

6181 25061

CFTR- IntronlO- - AUUAACCGGUGUCUUCUGAAAUA 23

6182 25062

CFTR- IntronlO- - AAUUAACCGGUGUCUUCUGAAAUA 24

6183 25063

CFTR- IntronlO- - AGUGAUCCUAGAAUCAUA 18

6184 25064

CFTR- IntronlO- - AAGUGAUCCUAGAAUCAUA 19

6185 25065

CFTR- IntronlO- - AAAGUGAUCCUAGAAUCAUA 20

6186 25066

CFTR- IntronlO- - UAAAGUGAUCCUAGAAUCAUA 21

6187 25067

CFTR- IntronlO- - AUAAAGUGAUCCUAGAAUCAUA 22

6188 25068

1028

5535.1 CFTR- IntronlO- - UAUAAAGUGAUCCUAGAAUCAUA 23

6189 25069

CFTR- IntronlO- - AUAUAAAGUGAUCCUAGAAUCAUA 24

6190 25070

CFTR- IntronlO- - CCGUUUACUAGAAAGAUA 18

6191 25071

CFTR- IntronlO- - GCCGUUUACUAGAAAGAUA 19

6192 25072

CFTR- IntronlO- - UGCCGUUUACUAGAAAGAUA 20

6193 25073

CFTR- IntronlO- - GUGCCGUUUACUAGAAAGAUA 21

6194 25074

CFTR- IntronlO- - UGUGCCGUUUACUAGAAAGAUA 22

6195 25075

CFTR- IntronlO- - AUGUGCCGUUUACUAGAAAGAUA 23

6196 25076

CFTR- IntronlO- - AAUGUGCCGUUUACUAGAAAGAUA 24

6197 25077

CFTR- IntronlO- - CUUGGUAUUUACCAUAUA 18

6198 25078

CFTR- IntronlO- - GCUUGGUAUUUACCAUAUA 19

6199 25079

CFTR- IntronlO- - UGCUUGGUAUUUACCAUAUA 20

6200 25080

CFTR- IntronlO- - UUGCUUGGUAUUUACCAUAUA 21

6201 25081

CFTR- IntronlO- - GUUGCUUGGUAUUUACCAUAUA 22

6202 25082

1029

5535.1 CFTR- IntronlO- - AGUUGCUUGGUAUUUACCAUAUA 23

6203 25083

CFTR- IntronlO- - GAGUUGCUUGGUAUUUACCAUAUA 24

6204 25084

CFTR- IntronlO- - UUACACUCUAGCAUUAUA 18

6205 25085

CFTR- IntronlO- - AUUACACUCUAGCAUUAUA 19

6206 25086

CFTR- IntronlO- - AAUUACACUCUAGCAUUAUA 20

6207 25087

CFTR- IntronlO- - UAAUUACACUCUAGCAUUAUA 21

6208 25088

CFTR- IntronlO- - AUAAUUACACUCUAGCAUUAUA 22

6209 25089

CFTR- IntronlO- - UAUAAUUACACUCUAGCAUUAUA 23

6210 25090

CFTR- IntronlO- - UUAUAAUUACACUCUAGCAUUAUA 24

6211 25091

CFTR- IntronlO- - AAAGUUUCUCAUCUUAUA 18

6212 25092

CFTR- IntronlO- - AAAAGUUUCUCAUCUUAUA 19

6213 25093

CFTR- IntronlO- - AAAAAGUUUCUCAUCUUAUA 20

1171 20056

CFTR- IntronlO- - UAAAAAGUUUCUCAUCUUAUA 21

6214 25094

CFTR- IntronlO- - UUAAAAAGUUUCUCAUCUUAUA 22

6215 25095

1030

5535.1 CFTR- IntronlO- - UUUAAAAAGUUUCUCAUCUUAUA 23

6216 25096

CFTR- IntronlO- - AUUUAAAAAGUUUCUCAUCUUAUA 24

6217 25097

CFTR- IntronlO- - GUACAAAGGAAUUUUAUA 18

6218 25098

CFTR- IntronlO- - UGUACAAAGGAAUUUUAUA 19

6219 25099

CFTR- IntronlO- - UUGUACAAAGGAAUUUUAUA 20

6220 25100

CFTR- IntronlO- - UU UGUACAAAGGAAUUUUAUA 21

6221 25101

CFTR- IntronlO- - UUUUGUACAAAGGAAUUUUAUA 22

6222 25102

CFTR- IntronlO- - AU U U UG U ACAAAGG AAU U U U AU A 23

6223 25103

CFTR- IntronlO- - AAU U U UG U ACAAAGG AAU U U U AU A 24

6224 25104

CFTR- IntronlO- - CUUGCUCUCUUUUAACUA 18

6225 25105

CFTR- IntronlO- - ACUUGCUCUCUUUUAACUA 19

6226 25106

CFTR- IntronlO- - AACUUGCUCUCUUUUAACUA 20

6227 25107

CFTR- IntronlO- - AAACUUGCUCUCUUUUAACUA 21

6228 25108

CFTR- IntronlO- - AAAACUUGCUCUCUUUUAACUA 22

6229 25109

1031

5535.1 CFTR- IntronlO- - AAAAACUUGCUCUCUUUUAACUA 23

6230 25110

CFTR- IntronlO- - UAAAAACUUGCUCUCUUUUAACUA 24

6231 25111

CFTR- IntronlO- - U AU U AAAAAAU U AU ACU A 18

6232 25112

CFTR- IntronlO- - CU AU U AAAAAAU U AU ACU A 19

6233 25113

CFTR- IntronlO- - ACUAUUAAAAAAUUAUACUA 20

6234 25114

CFTR- IntronlO- - CACU AU U AAAAAAU UAU ACU A 21

6235 25115

CFTR- IntronlO- - U CACU AU U AAAAAAU UAU ACU A 22

6236 25116

CFTR- IntronlO- - U U CACU AU U AAAAAAU UAU ACU A 23

6237 25117

CFTR- IntronlO- - GUUCACUAUUAAAAAAUUAUACUA 24

6238 25118

CFTR- IntronlO- - UUGACCUAAGAUAUCCUA 18

6239 25119

CFTR- IntronlO- - UUUGACCUAAGAUAUCCUA 19

6240 25120

CFTR-

- CUUUGACCUAAGAUAUCCUA 20

lntronlO-387 19273

CFTR- IntronlO- - UCUUUGACCUAAGAUAUCCUA 21

6241 25121

CFTR- IntronlO- - CUCUUUGACCUAAGAUAUCCUA 22

6242 25122

CFTR-

- CCUCUUUGACCUAAGAUAUCCUA 23

IntronlO- 25123

1032

5535.1 6243

CFTR- IntronlO- - UCCUCUUUGACCUAAGAUAUCCUA 24

6244 25124

CFTR- IntronlO- - UAGUAUUAGAAUGGGCUA 18

6245 25125

CFTR- IntronlO- - CUAGUAUUAGAAUGGGCUA 19

6246 25126

CFTR- IntronlO- - UCUAGUAUUAGAAUGGGCUA 20

6247 25127

CFTR- IntronlO- - UUCUAGUAUUAGAAUGGGCUA 21

6248 25128

CFTR- IntronlO- - UUUCUAGUAUUAGAAUGGGCUA 22

6249 25129

CFTR- IntronlO- - CUUUCUAGUAUUAGAAUGGGCUA 23

6250 25130

CFTR- IntronlO- - GCUUUCUAGUAUUAGAAUGGGCUA 24

6251 25131

CFTR- IntronlO- - GGGCUGGAUAAGAUUCUA 18

6252 25132

CFTR- IntronlO- - GGGGCUGGAUAAGAUUCUA 19

6253 25133

CFTR- IntronlO- - UGGGGCUGGAUAAGAUUCUA 20

6254 25134

CFTR- IntronlO- - AUGGGGCUGGAUAAGAUUCUA 21

6255 25135

CFTR- IntronlO- - GAUGGGGCUGGAUAAGAUUCUA 22

6256 25136

CFTR-

- AGAUGGGGCUGGAUAAGAUUCUA 23

IntronlO- 25137

1033

5535.1 6257

CFTR- IntronlO- - AAGAUGGGGCUGGAUAAGAUUCUA 24

6258 25138

CFTR- IntronlO- - CUGGUUUGAAGAACAGUA 18

6259 25139

CFTR- IntronlO- - UCUGGUUUGAAGAACAGUA 19

6260 25140

CFTR-

- GUCUGGUUUGAAGAACAGUA 20

lntronlO-86 18972

CFTR- IntronlO- - UGUCUGGUUUGAAGAACAGUA 21

6261 25141

CFTR- IntronlO- - CUGUCUGGUUUGAAGAACAGUA 22

6262 25142

CFTR- IntronlO- - CCUGUCUGGUUUGAAGAACAGUA 23

6263 25143

CFTR- IntronlO- - ACCUGUCUGGUUUGAAGAACAGUA 24

6264 25144

CFTR- IntronlO- - CUGGCACCAUUCACAGUA 18

6265 25145

CFTR- IntronlO- - CCUGGCACCAUUCACAGUA 19

6266 25146

CFTR- IntronlO- - ACCUGGCACCAUUCACAGUA 20

6267 25147

CFTR- IntronlO- - UACCUGGCACCAUUCACAGUA 21

6268 25148

CFTR- IntronlO- - CUACCUGGCACCAUUCACAGUA 22

6269 25149

CFTR- IntronlO- - CCUACCUGGCACCAUUCACAGUA 23

6270 25150

1034

5535.1 CFTR- IntronlO- - CCCUACCUGGCACCAUUCACAGUA 24

6271 25151

CFTR- IntronlO- - U U A A U G A A AG C A A U AG U A 18

6272 25152

CFTR- IntronlO- - CUUAAUGAAAGCAAUAGUA 19

6273 25153

CFTR- IntronlO- - ACUUAAUGAAAGCAAUAGUA 20

6274 25154

CFTR- IntronlO- - GACUUAAUGAAAGCAAUAGUA 21

6275 25155

CFTR- IntronlO- - UGACUUAAUGAAAGCAAUAGUA 22

6276 25156

CFTR- IntronlO- - GUGACUUAAUGAAAGCAAUAGUA 23

6277 25157

CFTR- IntronlO- - CGUGACUUAAUGAAAGCAAUAGUA 24

6278 25158

CFTR- IntronlO- - GGCUUGAUCCAGGUAGUA 18

6279 25159

CFTR- IntronlO- - UGGCUUGAUCCAGGUAGUA 19

6280 25160

CFTR- IntronlO- - GUGGCUUGAUCCAGGUAGUA 20

6281 25161

CFTR- IntronlO- - GGUGGCUUGAUCCAGGUAGUA 21

6282 25162

CFTR- IntronlO- - UGGUGGCUUGAUCCAGGUAGUA 22

6283 25163

CFTR- IntronlO- - AUGGUGGCUUGAUCCAGGUAGUA 23

6284 25164

1035

5535.1 CFTR- IntronlO- - GAUGGUGGCUUGAUCCAGGUAGUA 24

6285 25165

CFTR- IntronlO- - UUUUUAGGCUAUUCUGUA 18

6286 25166

CFTR- IntronlO- - GUUUUUAGGCUAUUCUGUA 19

6287 25167

CFTR-

- UGUUUUUAGGCUAUUCUGUA 20

lntronlO-390 19276

CFTR- IntronlO- - AUGUUUUUAGGCUAUUCUGUA 21

6288 25168

CFTR- IntronlO- - AAUGUUUUUAGGCUAUUCUGUA 22

6289 25169

CFTR- IntronlO- - UAAUGUUUUUAGGCUAUUCUGUA 23

6290 25170

CFTR- IntronlO- - CUAAUGUUUUUAGGCUAUUCUGUA 24

6291 25171

CFTR- IntronlO- - CACUUGACAGGUAUAUUA 18

6292 25172

CFTR- IntronlO- - GCACUUGACAGGUAUAUUA 19

6293 25173

CFTR- IntronlO- - AGCACUUGACAGGUAUAUUA 20

6294 25174

CFTR- IntronlO- - UAGCACUUGACAGGUAUAUUA 21

6295 25175

CFTR- IntronlO- - CUAGCACUUGACAGGUAUAUUA 22

6296 25176

CFTR- IntronlO- - CCUAGCACUUGACAGGUAUAUUA 23

6297 25177

CFTR-

- GCCUAGCACUUGACAGGUAUAUUA 24

IntronlO- 25178

1036

5535.1 6298

CFTR- IntronlO- - GAGAUAACUCGUGACUUA 18

6299 25179

CFTR- IntronlO- - GGAGAUAACUCGUGACUUA 19

6300 25180

CFTR- IntronlO- - CGGAGAUAACUCGUGACUUA 20

6301 25181

CFTR- IntronlO- - ACGGAGAUAACUCGUGACUUA 21

6302 25182

CFTR- IntronlO- - UACGGAGAUAACUCGUGACUUA 22

6303 25183

CFTR- IntronlO- - AUACGGAGAUAACUCGUGACUUA 23

6304 25184

CFTR- IntronlO- - AAUACGGAGAUAACUCGUGACUUA 24

6305 25185

CFTR- IntronlO- - U U UAU AAAAG AAACCU U A 18

6306 25186

CFTR- IntronlO- - CU U UAU AAAAG AAACCU U A 19

6307 25187

CFTR- IntronlO- - U CU U UAU AAAAG AAACCU U A 20

6308 25188

CFTR- IntronlO- - G U CU U UAU AAAAG AAACCU U A 21

6309 25189

CFTR- IntronlO- - UG U CU U UAU AAAAG AAACCU U A 22

6310 25190

CFTR- IntronlO- - G UG U CU U UAU AAAAG AAACCU U A 23

6311 25191

CFTR-

- AGUGUCUUUAUAAAAGAAACCUUA 24

IntronlO- 25192

1037

5535.1 6312

CFTR- IntronlO- - AGAGACCCUCACACCUUA 18

6313 25193

CFTR- IntronlO- - GAGAGACCCUCACACCUUA 19

6314 25194

CFTR- IntronlO- - AGAGAGACCCUCACACCUUA 20

6315 25195

CFTR- IntronlO- - UAGAGAGACCCUCACACCUUA 21

6316 25196

CFTR- IntronlO- - UUAGAGAGACCCUCACACCUUA 22

6317 25197

CFTR- IntronlO- - CUUAGAGAGACCCUCACACCUUA 23

6318 25198

CFTR- IntronlO- - CCUUAGAGAGACCCUCACACCUUA 24

6319 25199

CFTR- IntronlO- - AAAAAGUUUCUCAUCUUA 18

6320 25200

CFTR- IntronlO- - UAAAAAGUUUCUCAUCUUA 19

6321 25201

CFTR- IntronlO- - UUAAAAAGUUUCUCAUCUUA 20

6322 25202

CFTR- IntronlO- - UUUAAAAAGUUUCUCAUCUUA 21

6323 25203

CFTR- IntronlO- - AUUUAAAAAGUUUCUCAUCUUA 22

6324 25204

CFTR- IntronlO- - AAU U U AAAAAG UUUCUCAUCUUA 23

6325 25205

CFTR-

- UAAUUUAAAAAGUUUCUCAUCUUA 24

IntronlO- 25206

1038

5535.1 6326

CFTR- IntronlO- - GCUAUGAAGGCAGAGUUA 18

6327 25207

CFTR- IntronlO- - AGCUAUGAAGGCAGAGUUA 19

6328 25208

CFTR- IntronlO- - CAGCUAUGAAGGCAGAGUUA 20

6329 25209

CFTR- IntronlO- - GCAGCUAUGAAGGCAGAGUUA 21

6330 25210

CFTR- IntronlO- - AGCAGCUAUGAAGGCAGAGUUA 22

6331 25211

CFTR- IntronlO- - AAGCAGCUAUGAAGGCAGAGUUA 23

6332 25212

CFTR- IntronlO- - AAAGCAGCUAUGAAGGCAGAGUUA 24

6333 25213

CFTR- IntronlO- - UCUAAGUAUUAGAGGUUA 18

6334 25214

CFTR- IntronlO- - UUCUAAGUAUUAGAGGUUA 19

6335 25215

CFTR-

- AUUCUAAGUAUUAGAGGUUA 20

lntronlO-397 19283

CFTR- IntronlO- - CAU UCUAAGUAUUAGAGGUUA 21

6336 25216

CFTR- IntronlO- - GCAU UCUAAGUAUUAGAGGUUA 22

6337 25217

CFTR- IntronlO- - GGCAUUCUAAGUAUUAGAGGUUA 23

6338 25218

CFTR- IntronlO- - GGGCAUUCUAAGUAUUAGAGGUUA 24

6339 25219

1039

5535.1 CFTR- IntronlO- - CUGUAGGUAAAAAUGUUA 18

6340 25220

CFTR- IntronlO- - GCUGUAGGUAAAAAUGUUA 19

6341 25221

CFTR- IntronlO- - UGCUGUAGGUAAAAAUGUUA 20

6342 25222

CFTR- IntronlO- - CUGCUGUAGGUAAAAAUGUUA 21

6343 25223

CFTR- IntronlO- - GCUGCUGUAGGUAAAAAUGUUA 22

6344 25224

CFTR- IntronlO- - UGCUGCUGUAGGUAAAAAUGUUA 23

6345 25225

CFTR- IntronlO- - CUGCUGCUGUAGGUAAAAAUGUUA 24

6346 25226

CFTR- IntronlO- - U AAG AAU UG U AAAAU U U A 18

6347 25227

CFTR- IntronlO- - AU AAG AAU UG U AAAAU U U A 19

6348 25228

CFTR- IntronlO- - AAU AAG AAU UG U AAAAU U U A 20

6349 25229

CFTR- IntronlO- - U AAU AAG AAU UG U AAAAU U U A 21

6350 25230

CFTR- IntronlO- - G U AAU AAG AAU UG U AAAAU U U A 22

6351 25231

CFTR- IntronlO- - UG U AAU AAG AAU UG U AAAAU U U A 23

6352 25232

CFTR- IntronlO- - AUG U AAU AAG AAU UG U AAAAU U U A 24

6353 25233

1040

5535.1 CFTR- IntronlO- - CUUCCUUGAAUUAUUUUA 18

6354 25234

CFTR- IntronlO- - ACUUCCUUGAAUUAUUUUA 19

6355 25235

CFTR- IntronlO- - AACUUCCUUGAAUUAUUUUA 20

6356 25236

CFTR- IntronlO- - AAACUUCCUUGAAUUAUUUUA 21

6357 25237

CFTR- IntronlO- - GAAACUUCCUUGAAUUAUUUUA 22

6358 25238

CFTR- IntronlO- - UGAAACUUCCUUGAAUUAUUUUA 23

6359 25239

CFTR- IntronlO- - AUGAAACUUCCUUGAAUUAUUUUA 24

6360 25240

CFTR- IntronlO- - UGUUAUAGCAGCCUGAAC 18

6361 25241

CFTR- IntronlO- - UUGUUAUAGCAGCCUGAAC 19

6362 25242

CFTR- IntronlO- - UUUGUUAUAGCAGCCUGAAC 20

6363 25243

CFTR- IntronlO- - UUUUGUUAUAGCAGCCUGAAC 21

6364 25244

CFTR- IntronlO- - AUUUUGUUAUAGCAGCCUGAAC 22

6365 25245

CFTR- IntronlO- - UAUUUUGUUAUAGCAGCCUGAAC 23

6366 25246

CFTR- IntronlO- - GUAUUUUGUUAUAGCAGCCUGAAC 24

6367 25247

1041

5535.1 CFTR- IntronlO- - GCUUAUUCUUGUAAUAAC 18

6368 25248

CFTR- IntronlO- - AGCUUAUUCUUGUAAUAAC 19

6369 25249

CFTR-

- UAGCUUAUUCUUGUAAUAAC 20

Intron 10-404 19290

CFTR- IntronlO- - UUAGCUUAUUCUUGUAAUAAC 21

6370 25250

CFTR- IntronlO- - UUUAGCUUAUUCUUGUAAUAAC 22

6371 25251

CFTR- IntronlO- - UUUUAGCUUAUUCUUGUAAUAAC 23

6372 25252

CFTR- IntronlO- - GUUUUAGCUUAUUCUUGUAAUAAC 24

6373 25253

CFTR- IntronlO- - GGCCUGCAUAUGUCUAAC 18

6374 25254

CFTR- IntronlO- - GGGCCUGCAUAUGUCUAAC 19

6375 25255

CFTR- IntronlO- - UGGGCCUGCAUAUGUCUAAC 20

6376 25256

CFTR- IntronlO- - UUGGGCCUGCAUAUGUCUAAC 21

6377 25257

CFTR- IntronlO- - UUUGGGCCUGCAUAUGUCUAAC 22

6378 25258

CFTR- IntronlO- - AUUUGGGCCUGCAUAUGUCUAAC 23

6379 25259

CFTR- IntronlO- - UAUUUGGGCCUGCAUAUGUCUAAC 24

6380 25260

CFTR-

- CUUUCUGGACUGAGUAAC 18

IntronlO- 25261

1042

5535.1 6381

CFTR- IntronlO- - GCUUUCUGGACUGAGUAAC 19

6382 25262

CFTR- IntronlO- - AGCUUUCUGGACUGAGUAAC 20

1182 20067

CFTR- IntronlO- - AAGCUUUCUGGACUGAGUAAC 21

6383 25263

CFTR- IntronlO- - CAAGCUUUCUGGACUGAGUAAC 22

6384 25264

CFTR- IntronlO- - CCAAGCUUUCUGGACUGAGUAAC 23

6385 25265

CFTR- IntronlO- - UCCAAGCUUUCUGGACUGAGUAAC 24

6386 25266

CFTR- IntronlO- - UCAUUUCAACUUAUACAC 18

6387 25267

CFTR- IntronlO- - AUCAUUUCAACUUAUACAC 19

6388 25268

CFTR-

- UAUCAUUUCAACUUAUACAC 20

lntronlO-407 19293

CFTR- IntronlO- - AUAUCAUUUCAACUUAUACAC 21

6389 25269

CFTR- IntronlO- - AAUAUCAUUUCAACUUAUACAC 22

6390 25270

CFTR- IntronlO- - AAAUAUCAUUUCAACUUAUACAC 23

6391 25271

CFTR- IntronlO- - AAAAU AU CAU U U CAACU UAU ACAC 24

6392 25272

CFTR- IntronlO- - GGUGAGAUUAGAGGCCAC 18

6393 25273

1043

5535.1 CFTR- IntronlO- - GGGUGAGAUUAGAGGCCAC 19

6394 25274

CFTR-

- UGGGUGAGAUUAGAGGCCAC 20

lntronlO-409 19295

CFTR- IntronlO- - CUGGGUGAGAUUAGAGGCCAC 21

6395 25275

CFTR- IntronlO- - UCUGGGUGAGAUUAGAGGCCAC 22

6396 25276

CFTR- IntronlO- - CUCUGGGUGAGAUUAGAGGCCAC 23

6397 25277

CFTR- IntronlO- - UCUCUGGGUGAGAUUAGAGGCCAC 24

6398 25278

CFTR- IntronlO- - CUGAGGUGGGAGGAUCAC 18

6399 25279

CFTR- IntronlO- - GCUGAGGUGGGAGGAUCAC 19

6400 25280

CFTR- IntronlO- - GGCUGAGGUGGGAGGAUCAC 20

6401 25281

CFTR- IntronlO- - AGGCUGAGGUGGGAGGAUCAC 21

6402 25282

CFTR- IntronlO- - GAGGCUGAGGUGGGAGGAUCAC 22

6403 25283

CFTR- IntronlO- - GGAGGCUGAGGUGGGAGGAUCAC 23

6404 25284

CFTR- IntronlO- - GGGAGGCUGAGGUGGGAGGAUCAC 24

6405 25285

CFTR- IntronlO- - GUUUGUCUUUAAUUUCAC 18

6406 25286

CFTR-

- GGUUUGUCUUUAAUUUCAC 19

IntronlO- 25287

1044

5535.1 6407

CFTR- IntronlO- - AGGUUUGUCUUUAAUUUCAC 20

6408 25288

CFTR- IntronlO- - UAGGUUUGUCUUUAAUUUCAC 21

6409 25289

CFTR- IntronlO- - UUAGGUUUGUCUUUAAUUUCAC 22

6410 25290

CFTR- IntronlO- - GUUAGGUUUGUCUUUAAUUUCAC 23

6411 25291

CFTR- IntronlO- - AGUUAGGUUUGUCUUUAAUUUCAC 24

6412 25292

CFTR- IntronlO- - GG AAAU AAAU U U AAAG AC 18

6413 25293

CFTR- IntronlO- - AGG AAAU AAAU U U AAAG AC 19

6414 25294

CFTR- IntronlO- - G AGG AAAU AAAU U U AAAG AC 20

6415 25295

CFTR- IntronlO- - UG AGGAAAU AAAU UU AAAG AC 21

6416 25296

CFTR- IntronlO- - U U G AGG AAAU AAAU U U AAAG AC 22

6417 25297

CFTR- IntronlO- - AU UG AGG AAAU AAAU U U AAAG AC 23

6418 25298

CFTR- IntronlO- - U AU UG AGG AAAU AAAU U U AAAG AC 24

6419 25299

CFTR- IntronlO- - GCUGGCAUAGAGUAAGAC 18

6420 25300

CFTR-

- GGCUGGCAUAGAGUAAGAC 19

IntronlO- 25301

1045

5535.1 6421

CFTR-

- AGGCUGGCAUAGAGUAAGAC 20

lntronlO-412 19298

CFTR- IntronlO- - GAGGCUGGCAUAGAGUAAGAC 21

6422 25302

CFTR- IntronlO- - UGAGGCUGGCAUAGAGUAAGAC 22

6423 25303

CFTR- IntronlO- - CUGAGGCUGGCAUAGAGUAAGAC 23

6424 25304

CFTR- IntronlO- - ACUGAGGCUGGCAUAGAGUAAGAC 24

6425 25305

CFTR- IntronlO- - GCUAUUCUGUAGGGAGAC 18

6426 25306

CFTR- IntronlO- - GGCUAUUCUGUAGGGAGAC 19

6427 25307

CFTR- IntronlO- - AGGCUAUUCUGUAGGGAGAC 20

6428 25308

CFTR- IntronlO- - UAGGCUAUUCUGUAGGGAGAC 21

6429 25309

CFTR- IntronlO- - UU AGGCUAUUCUGUAGGGAGAC 22

6430 25310

CFTR- IntronlO- - UUUAGGCUAUUCUGUAGGGAGAC 23

6431 25311

CFTR- IntronlO- - UUUUAGGCUAUUCUGUAGGGAGAC 24

6432 25312

CFTR- IntronlO- - AAGAAUUGAAUAUGAGAC 18

6433 25313

CFTR- IntronlO- - GAAGAAUUGAAUAUGAGAC 19

6434 25314

1046

5535.1 CFTR- IntronlO- - UGAAGAAUUGAAUAUGAGAC 20

6435 25315

CFTR- IntronlO- - UUGAAGAAUUGAAUAUGAGAC 21

6436 25316

CFTR- IntronlO- - UUUGAAGAAUUGAAUAUGAGAC 22

6437 25317

CFTR- IntronlO- - UUUUGAAGAAUUGAAUAUGAGAC 23

6438 25318

CFTR- IntronlO- - AUUUUGAAGAAUUGAAUAUGAGAC 24

6439 25319

CFTR- IntronlO- - GCCCGUAGUCCCAGCUAC 18

6440 25320

CFTR- IntronlO- - UGCCCGUAGUCCCAGCUAC 19

6441 25321

CFTR- IntronlO- - GUGCCCGUAGUCCCAGCUAC 20

6442 25322

CFTR- IntronlO- - GGUGCCCGUAGUCCCAGCUAC 21

6443 25323

CFTR- IntronlO- - GGGUGCCCGUAGUCCCAGCUAC 22

6444 25324

CFTR- IntronlO- - CGGGUGCCCGUAGUCCCAGCUAC 23

6445 25325

CFTR- IntronlO- - GCGGGUGCCCGUAGUCCCAGCUAC 24

6446 25326

CFTR- IntronlO- - UGUGCCUGUAGUCCCAGCUAC 21

6447 25327

CFTR- IntronlO- - GUGUGCCUGUAGUCCCAGCUAC 22

6448 25328

1047

5535.1 CFTR- IntronlO- - UGUGUGCCUGUAGUCCCAGCUAC 23

6449 25329

CFTR- IntronlO- - GUGUGUGCCUGUAGUCCCAGCUAC 24

6450 25330

CFTR- IntronlO- - GAAAAG UUGUAACAG U AC 18

6451 25331

CFTR- IntronlO- - GGAAAAGUUGUAACAGUAC 19

6452 25332

CFTR- IntronlO- - CGGAAAAG UUGUAACAG U AC 20

6453 25333

CFTR- IntronlO- - ACGGAAAAGUUGUAACAGUAC 21

6454 25334

CFTR- IntronlO- - CACGG AAAAG UUGUAACAG U AC 22

6455 25335

CFTR- IntronlO- - GCACGGAAAAGUUGUAACAGUAC 23

6456 25336

CFTR- IntronlO- - UGCACGGAAAAGUUGUAACAGUAC 24

6457 25337

CFTR- IntronlO- - GAUAAAUGUGCCGUUUAC 18

6458 25338

CFTR- IntronlO- - GGAUAAAUGUGCCGUUUAC 19

6459 25339

CFTR- IntronlO- - AGGAUAAAUGUGCCGUUUAC 20

6460 25340

CFTR- IntronlO- - AAGGAUAAAUGUGCCGUUUAC 21

6461 25341

CFTR- IntronlO- - GAAGGAUAAAUGUGCCGUUUAC 22

6462 25342

1048

5535.1 CFTR- IntronlO- - GGAAGGAUAAAUGUGCCGUUUAC 23

6463 25343

CFTR- IntronlO- - UGGAAGGAUAAAUGUGCCGUUUAC 24

6464 25344

CFTR- IntronlO- - UCAUAGCUCACUGUAACC 18

6465 25345

CFTR- IntronlO- - AUCAUAGCUCACUGUAACC 19

6466 25346

CFTR- IntronlO- - GAUCAUAGCUCACUGUAACC 20

6467 25347

CFTR- IntronlO- - UGAUCAUAGCUCACUGUAACC 21

6468 25348

CFTR- IntronlO- - GUGAUCAUAGCUCACUGUAACC 22

6469 25349

CFTR- IntronlO- - UGUGAUCAUAGCUCACUGUAACC 23

6470 25350

CFTR- IntronlO- - GUGUGAUCAUAGCUCACUGUAACC 24

6471 25351

CFTR- IntronlO- - GUCUAGCCUAGAAAUACC 18

6472 25352

CFTR- IntronlO- - UGUCUAGCCUAGAAAUACC 19

6473 25353

CFTR- IntronlO- - CUGUCUAGCCUAGAAAUACC 20

6474 25354

CFTR- IntronlO- - ACUGUCUAGCCUAGAAAUACC 21

6475 25355

CFTR- IntronlO- - AACUGUCUAGCCUAGAAAUACC 22

6476 25356

1049

5535.1 CFTR- IntronlO- - AAACUGUCUAGCCUAGAAAUACC 23

6477 25357

CFTR- IntronlO- - CAAACUGUCUAGCCUAGAAAUACC 24

6478 25358

CFTR- IntronlO- - GAGGAAGGCAGUGGUCCC 18

6479 25359

CFTR- IntronlO- - AGAGGAAGGCAGUGGUCCC 19

6480 25360

CFTR- IntronlO- - UAGAGGAAGGCAGUGGUCCC 20

6481 25361

CFTR- IntronlO- - UU AGAGGAAGGCAGUGGUCCC 21

6482 25362

CFTR- IntronlO- - GUUAGAGGAAGGCAGUGGUCCC 22

6483 25363

CFTR- IntronlO- - AGUUAGAGGAAGGCAGUGGUCCC 23

6484 25364

CFTR- IntronlO- - GAGUUAGAGGAAGGCAGUGGUCCC 24

6485 25365

CFTR- IntronlO- - CUCACAAACUGUCUAGCC 18

6486 25366

CFTR- IntronlO- - ACUCACAAACUGUCUAGCC 19

6487 25367

CFTR- IntronlO- - AACUCACAAACUGUCUAGCC 20

6488 25368

CFTR- IntronlO- - AAACUCACAAACUGUCUAGCC 21

6489 25369

CFTR- IntronlO- - AAAACUCACAAACUGUCUAGCC 22

6490 25370

1050

5535.1 CFTR- IntronlO- - AAAAACUCACAAACUGUCUAGCC 23

6491 25371

CFTR- IntronlO- - AAAAAACUCACAAACUGUCUAGCC 24

6492 25372

CFTR- IntronlO- - UGAAUGAAUGUGGUAUCC 18

6493 25373

CFTR- IntronlO- - GUGAAUGAAUGUGGUAUCC 19

6494 25374

CFTR-

- AGUGAAUGAAUGUGGUAUCC 20

lntronlO-425 19311

CFTR- IntronlO- - UAGUGAAUGAAUGUGGUAUCC 21

6495 25375

CFTR- IntronlO- - CUAGUGAAUGAAUGUGGUAUCC 22

6496 25376

CFTR- IntronlO- - GCUAGUGAAUGAAUGUGGUAUCC 23

6497 25377

CFTR- IntronlO- - AGCUAGUGAAUGAAUGUGGUAUCC 24

6498 25378

CFTR- IntronlO- - UUGGGAGGUGAUUAGUCC 18

6499 25379

CFTR- IntronlO- - UUUGGGAGGUGAUUAGUCC 19

6500 25380

CFTR- IntronlO- - CUUUGGGAGGUGAUUAGUCC 20

6501 25381

CFTR- IntronlO- - CCUUUGGGAGGUGAUUAGUCC 21

6502 25382

CFTR- IntronlO- - GCCUUUGGGAGGUGAUUAGUCC 22

6503 25383

CFTR-

- GGCCUUUGGGAGGUGAUUAGUCC 23

IntronlO- 25384

1051

5535.1 6504

CFTR- IntronlO- - GGGCCUUUGGGAGGUGAUUAGUCC 24

6505 25385

CFTR- IntronlO- - UCUUUAUUUUUAUAUUCC 18

6506 25386

CFTR- IntronlO- - UUCUUUAUUUUUAUAUUCC 19

6507 25387

CFTR- IntronlO- - CUUCUUUAUUUUUAUAUUCC 20

6508 25388

CFTR- IntronlO- - UCUUCUUUAUUUUUAUAUUCC 21

6509 25389

CFTR- IntronlO- - GUCUUCUUUAUUUUUAUAUUCC 22

6510 25390

CFTR- IntronlO- - UGUCUUCUUUAUUUUUAUAUUCC 23

6511 25391

CFTR- IntronlO- - AUGUCUUCUUUAUUUUUAUAUUCC 24

6512 25392

CFTR- IntronlO- - GUUGUCAAAUGUCCUUCC 18

6513 25393

CFTR- IntronlO- - UGUUGUCAAAUGUCCUUCC 19

6514 25394

CFTR- IntronlO- - AUGUUGUCAAAUGUCCUUCC 20

6515 25395

CFTR- IntronlO- - GAUGUUGUCAAAUGUCCUUCC 21

6516 25396

CFTR- IntronlO- - AGAUGUUGUCAAAUGUCCUUCC 22

6517 25397

CFTR-

- UAGAUGUUGUCAAAUGUCCUUCC 23

IntronlO- 25398

1052

5535.1 6518

CFTR- IntronlO- - GUAGAUGUUGUCAAAUGUCCUUCC 24

6519 25399

CFTR- IntronlO- - CUUUUUUUAGUAUCUUCC 18

6520 25400

CFTR- IntronlO- - ACUUUUUUUAGUAUCUUCC 19

6521 25401

CFTR- IntronlO- - AACUUUUUUUAGUAUCUUCC 20

6522 25402

CFTR- IntronlO- - UAACUUUUUUUAGUAUCUUCC 21

6523 25403

CFTR- IntronlO- - GUAACUUUUUUUAGUAUCUUCC 22

6524 25404

CFTR- IntronlO- - GGUAACUUUUUUUAGUAUCUUCC 23

6525 25405

CFTR- IntronlO- - AGGUAACUUUUUUUAGUAUCUUCC 24

6526 25406

CFTR- IntronlO- - GGAGACAAGGGAGGAAGC 18

6527 25407

CFTR- IntronlO- - GGGAGACAAGGGAGGAAGC 19

6528 25408

CFTR- IntronlO- - AGGGAGACAAGGGAGGAAGC 20

6529 25409

CFTR- IntronlO- - UAGGGAGACAAGGGAGGAAGC 21

6530 25410

CFTR- IntronlO- - GUAGGGAGACAAGGGAGGAAGC 22

6531 25411

CFTR-

- UGUAGGGAGACAAGGGAGGAAGC 23

IntronlO- 25412

1053

5535.1 6532

CFTR- IntronlO- - CUGUAGGGAGACAAGGGAGGAAGC 24

6533 25413

CFTR- IntronlO- - GCCAUGUGAGAACACAGC 18

6534 25414

CFTR- IntronlO- - UGCCAUGUGAGAACACAGC 19

6535 25415

CFTR- IntronlO- - CUGCCAUGUGAGAACACAGC 20

1218 20103

CFTR- IntronlO- - UCUGCCAUGUGAGAACACAGC 21

6536 25416

CFTR- IntronlO- - UUCUGCCAUGUGAGAACACAGC 22

6537 25417

CFTR- IntronlO- - UUUCUGCCAUGUGAGAACACAGC 23

6538 25418

CFTR- IntronlO- - CUUUCUGCCAUGUGAGAACACAGC 24

6539 25419

CFTR- IntronlO- - CAGGAGUUUGAGACCAGC 18

6540 25420

CFTR- IntronlO- - CCAGGAGUUUGAGACCAGC 19

6541 25421

CFTR- IntronlO- - UCCAGGAGUUUGAGACCAGC 20

6542 25422

CFTR- IntronlO- - GUCCAGGAGUUUGAGACCAGC 21

6543 25423

CFTR- IntronlO- - AGUCCAGGAGUUUGAGACCAGC 22

6544 25424

CFTR-

- G AG U CCAGG AG U U UG AG ACCAGC 23

IntronlO- 25425

1054

5535.1 6545

CFTR- IntronlO- - UGAGUCCAGGAGUUUGAGACCAGC 24

6546 25426

CFTR- IntronlO- - GUAUUUUGUUAUAGCAGC 18

6547 25427

CFTR- IntronlO- - GGUAUUUUGUUAUAGCAGC 19

6548 25428

CFTR- IntronlO- - UGGUAUUUUGUUAUAGCAGC 20

6549 25429

CFTR- IntronlO- - AUGGUAUUUUGUUAUAGCAGC 21

6550 25430

CFTR- IntronlO- - CAUGGUAUUUUGUUAUAGCAGC 22

6551 25431

CFTR- IntronlO- - UCAUGGUAUUUUGUUAUAGCAGC 23

6552 25432

CFTR- IntronlO- - UUCAUGGUAUUUUGUUAUAGCAGC 24

6553 25433

CFTR- IntronlO- - UGGGAGGAUCACCUGAGC 18

6554 25434

CFTR- IntronlO- - GUGGGAGGAUCACCUGAGC 19

6555 25435

CFTR- IntronlO- - GGUGGGAGGAUCACCUGAGC 20

6556 25436

CFTR- IntronlO- - AGGUGGGAGGAUCACCUGAGC 21

6557 25437

CFTR- IntronlO- - GAGGUGGGAGGAUCACCUGAGC 22

6558 25438

CFTR-

- UGAGGUGGGAGGAUCACCUGAGC 23

IntronlO- 25439

1055

5535.1 6559

CFTR- IntronlO- - CUGAGGUGGGAGGAUCACCUGAGC 24

6560 25440

CFTR- IntronlO- - CUCACCCUCCCAAGUAGC 18

6561 25441

CFTR- IntronlO- - CCUCACCCUCCCAAGUAGC 19

6562 25442

CFTR-

- GCCUCACCCUCCCAAGUAGC 20

lntronlO-672 19558

CFTR- IntronlO- - UGCCUCACCCUCCCAAGUAGC 21

6563 25443

CFTR- IntronlO- - CUGCCUCACCCUCCCAAGUAGC 22

6564 25444

CFTR- IntronlO- - CCUGCCUCACCCUCCCAAGUAGC 23

6565 25445

CFTR- IntronlO- - UCCUGCCUCACCCUCCCAAGUAGC 24

6566 25446

CFTR- IntronlO- - CUCAGCCUCCCAAGUAGC 18

6567 25447

CFTR- IntronlO- - CCUCAGCCUCCCAAGUAGC 19

6568 25448

CFTR-

- GCCUCAGCCUCCCAAGUAGC 20

lntronlO-673 19559

CFTR- IntronlO- - UGCCUCAGCCUCCCAAGUAGC 21

6569 25449

CFTR- IntronlO- - CUGCCUCAGCCUCCCAAGUAGC 22

6570 25450

CFTR- IntronlO- - CCUGCCUCAGCCUCCCAAGUAGC 23

6571 25451

1056

5535.1 CFTR- IntronlO- - UCCUGCCUCAGCCUCCCAAGUAGC 24

6572 25452

CFTR- IntronlO- - CCCUUAAACAAUACAGGC 18

6573 25453

CFTR- IntronlO- - ACCCU U AAACAAU ACAGGC 19

6574 25454

CFTR- IntronlO- - GACCCUUAAACAAUACAGGC 20

6575 25455

CFTR- IntronlO- - UG ACCCU U AAACAAU ACAGGC 21

6576 25456

CFTR- IntronlO- - UUGACCCUUAAACAAUACAGGC 22

6577 25457

CFTR- IntronlO- - AUUGACCCUUAAACAAUACAGGC 23

6578 25458

CFTR- IntronlO- - AAU UG ACCCU U AAACAAU ACAGG C 24

6579 25459

CFTR- IntronlO- - AGUGCUGGGAUUACAGGC 18

6580 25460

CFTR- IntronlO- - AAGUGCUGGGAUUACAGGC 19

6581 25461

CFTR- IntronlO- - AAAGUGCUGGGAUUACAGGC 20

6582 25462

CFTR- IntronlO- - CAAAGUGCUGGGAUUACAGGC 21

6583 25463

CFTR- IntronlO- - CCAAAGUGCUGGGAUUACAGGC 22

6584 25464

CFTR- IntronlO- - CCCAAAGUGCUGGGAUUACAGGC 23

6585 25465

1057

5535.1 CFTR- IntronlO- - UCCCAAAGUGCUGGGAUUACAGGC 24

6586 25466

CFTR- IntronlO- - AGUGUUGGGAUUACAGGC 18

6587 25467

CFTR- IntronlO- - AAGUGUUGGGAUUACAGGC 19

6588 25468

CFTR- IntronlO- - AAAGUGUUGGGAUUACAGGC 20

6589 25469

CFTR- IntronlO- - CAAAGUGUUGGGAUUACAGGC 21

6590 25470

CFTR- IntronlO- - CCAAAGUGUUGGGAUUACAGGC 22

6591 25471

CFTR- IntronlO- - CCCAAAGUGUUGGGAUUACAGGC 23

6592 25472

CFTR- IntronlO- - UCCCAAAGUGUUGGGAUUACAGGC 24

6593 25473

CFTR- IntronlO- - GUCUUACUGUCACCAGGC 18

6594 25474

CFTR- IntronlO- - AGUCUUACUGUCACCAGGC 19

6595 25475

CFTR-

- GAGUCUUACUGUCACCAGGC 20

lntronlO-677 19563

CFTR- IntronlO- - AGAGUCUUACUGUCACCAGGC 21

6596 25476

CFTR- IntronlO- - CAGAGUCUUACUGUCACCAGGC 22

6597 25477

CFTR- IntronlO- - ACAGAGUCUUACUGUCACCAGGC 23

6598 25478

CFTR-

- GACAGAGUCUUACUGUCACCAGGC 24

IntronlO- 25479

1058

5535.1 6599

CFTR- IntronlO- - UACUCGGGAGGCUGAGGC 18

6600 25480

CFTR- IntronlO- - CUACUCGGGAGGCUGAGGC 19

6601 25481

CFTR-

- GCUACUCGGGAGGCUGAGGC 20

lntronlO-680 19566

CFTR- IntronlO- - AGCUACUCGGGAGGCUGAGGC 21

6602 25482

CFTR- IntronlO- - CAGCUACUCGGGAGGCUGAGGC 22

6603 25483

CFTR- IntronlO- - CCAGCUACUCGGGAGGCUGAGGC 23

6604 25484

CFTR- IntronlO- - CCCAGCUACUCGGGAGGCUGAGGC 24

6605 25485

CFTR- IntronlO- - AGUGCUGGGUUUAUAGGC 18

6606 25486

CFTR- IntronlO- - AAGUGCUGGGUUUAUAGGC 19

6607 25487

CFTR- IntronlO- - AAAGUGCUGGGUUUAUAGGC 20

6608 25488

CFTR- IntronlO- - CAAAGUGCUGGGUUUAUAGGC 21

6609 25489

CFTR- IntronlO- - CCAAAGUGCUGGGUUUAUAGGC 22

6610 25490

CFTR- IntronlO- - CCCAAAGUGCUGGGUUUAUAGGC 23

6611 25491

CFTR- IntronlO- - UCCCAAAGUGCUGGGUUUAUAGGC 24

6612 25492

1059

5535.1 CFTR- IntronlO- - AAGUGCCACUAGUGAUGC 18

6613 25493

CFTR- IntronlO- - AAAGUGCCACUAGUGAUGC 19

6614 25494

CFTR- IntronlO- - CAAAGUGCCACUAGUGAUGC 20

6615 25495

CFTR- IntronlO- - ACAAAGUGCCACUAGUGAUGC 21

6616 25496

CFTR- IntronlO- - UACAAAGUGCCACUAGUGAUGC 22

6617 25497

CFTR- IntronlO- - AUACAAAGUGCCACUAGUGAUGC 23

6618 25498

CFTR- IntronlO- - CAUACAAAGUGCCACUAGUGAUGC 24

6619 25499

CFTR- IntronlO- - UCAAAUUAUUUCUACUGC 18

6620 25500

CFTR- IntronlO- - UUCAAAUUAUUUCUACUGC 19

6621 25501

CFTR- IntronlO- - GUUCAAAUUAUUUCUACUGC 20

6622 25502

CFTR- IntronlO- - UGUUCAAAUUAUUUCUACUGC 21

6623 25503

CFTR- IntronlO- - UUGUUCAAAUUAUUUCUACUGC 22

6624 25504

CFTR- IntronlO- - GUUGUUCAAAUUAUUUCUACUGC 23

6625 25505

CFTR- IntronlO- - UGUUGUUCAAAUUAUUUCUACUGC 24

6626 25506

1060

5535.1 CFTR- IntronlO- - AUUUGAACAAAGACUUGC 18

6627 25507

CFTR- IntronlO- - CAUUUGAACAAAGACUUGC 19

6628 25508

CFTR- IntronlO- - ACAUUUG AACAAAG ACU UGC 20

1236 20121

CFTR- IntronlO- - AACAUUUGAACAAAGACUUGC 21

6629 25509

CFTR- IntronlO- - UAACAUUUGAACAAAGACUUGC 22

6630 25510

CFTR- IntronlO- - G U AACAU U UG AACAAAG ACU UG C 23

6631 25511

CFTR- IntronlO- - G G U AACAU U U G AACAAAG AC U UGC 24

6632 25512

CFTR- IntronlO- - G AG U U U ACU AACU CAAU C 18

6633 25513

CFTR- IntronlO- - GGAGUUUACUAACUCAAUC 19

6634 25514

CFTR- IntronlO- - CGGAGUUUACUAACUCAAUC 20

6635 25515

CFTR- IntronlO- - ACGGAGUUUACUAACUCAAUC 21

6636 25516

CFTR- IntronlO- - AACGGAGUUUACUAACUCAAUC 22

6637 25517

CFTR- IntronlO- - AAACGGAGUUUACUAACUCAAUC 23

6638 25518

CFTR- IntronlO- - G AAACGG AG U U U ACU AACU CAAU C 24

6639 25519

1061

5535.1 CFTR- IntronlO- - UCUGCUGGCACCUUGAUC 18

6640 25520

CFTR- IntronlO- - AUCUGCUGGCACCUUGAUC 19

6641 25521

CFTR- IntronlO- - AAUCUGCUGGCACCUUGAUC 20

6642 25522

CFTR- IntronlO- - AAAUCUGCUGGCACCUUGAUC 21

6643 25523

CFTR- IntronlO- - CAAAUCUGCUGGCACCUUGAUC 22

6644 25524

CFTR- IntronlO- - CCAAAUCUGCUGGCACCUUGAUC 23

6645 25525

CFTR- IntronlO- - CCCAAAUCUGCUGGCACCUUGAUC 24

6646 25526

CFTR- IntronlO- - CUUGCUUUUCCCACUAUC 18

6647 25527

CFTR- IntronlO- - UCUUGCUUUUCCCACUAUC 19

6648 25528

CFTR- IntronlO- - UUCUUGCUUUUCCCACUAUC 20

6649 25529

CFTR- IntronlO- - CUUCUUGCUUUUCCCACUAUC 21

6650 25530

CFTR- IntronlO- - GCUUCUUGCUUUUCCCACUAUC 22

6651 25531

CFTR- IntronlO- - UGCUUCUUGCUUUUCCCACUAUC 23

6652 25532

CFTR- IntronlO- - UUGCUUCUUGCUUUUCCCACUAUC 24

6653 25533

1062

5535.1 CFTR- IntronlO- - GUGAAUGAAUGUGGUAUC 18

6654 25534

CFTR- IntronlO- - AGUGAAUGAAUGUGGUAUC 19

6655 25535

CFTR- IntronlO- - UAGUGAAUGAAUGUGGUAUC 20

6656 25536

CFTR- IntronlO- - CUAGUGAAUGAAUGUGGUAUC 21

6657 25537

CFTR- IntronlO- - GCUAGUGAAUGAAUGUGGUAUC 22

6658 25538

CFTR- IntronlO- - AGCUAGUGAAUGAAUGUGGUAUC 23

6659 25539

CFTR- IntronlO- - AAGCUAGUGAAUGAAUGUGGUAUC 24

6660 25540

CFTR- IntronlO- - CACUGUAACCUUGAACUC 18

6661 25541

CFTR- IntronlO- - UCACUGUAACCUUGAACUC 19

6662 25542

CFTR- IntronlO- - CUCACUGUAACCUUGAACUC 20

6663 25543

CFTR- IntronlO- - GCUCACUGUAACCUUGAACUC 21

6664 25544

CFTR- IntronlO- - AGCUCACUGUAACCUUGAACUC 22

6665 25545

CFTR- IntronlO- - UAGCUCACUGUAACCUUGAACUC 23

6666 25546

CFTR- IntronlO- - AUAGCUCACUGUAACCUUGAACUC 24

6667 25547

1063

5535.1 CFTR- IntronlO- - AGAAAUUAAGAAAGACUC 18

6668 25548

CFTR- IntronlO- - UAGAAAUUAAGAAAGACUC 19

6669 25549

CFTR- IntronlO- - A U AG AAA U U A AG A A AG AC U C 20

6670 25550

CFTR- IntronlO- - AAUAGAAAUUAAGAAAGACUC 21

6671 25551

CFTR- IntronlO- - AAAUAGAAAUUAAGAAAGACUC 22

6672 25552

CFTR- IntronlO- - AAAAUAGAAAUUAAGAAAGACUC 23

6673 25553

CFTR- IntronlO- - GAAAAUAGAAAUUAAGAAAGACUC 24

6674 25554

CFTR- IntronlO- - AUUAGGGAAUGCAGACUC 18

6675 25555

CFTR- IntronlO- - GAUUAGGGAAUGCAGACUC 19

6676 25556

CFTR-

- GGAUUAGGGAAUGCAGACUC 20

lntronlO-92 18978

CFTR- IntronlO- - GGGAUUAGGGAAUGCAGACUC 21

6677 25557

CFTR- IntronlO- - AGGGAUUAGGGAAUGCAGACUC 22

6678 25558

CFTR- IntronlO- - GAGGGAUUAGGGAAUGCAGACUC 23

6679 25559

CFTR- IntronlO- - UGAGGGAUUAGGGAAUGCAGACUC 24

6680 25560

CFTR-

- UAUUCUUUUGAUAUACUC 18

IntronlO- 25561

1064

5535.1 6681

CFTR- IntronlO- - UUAUUCUUUUGAUAUACUC 19

6682 25562

CFTR- IntronlO- - CUUAUUCUUUUGAUAUACUC 20

6683 25563

CFTR- IntronlO- - CCUUAUUCUUUUGAUAUACUC 21

6684 25564

CFTR- IntronlO- - GCCUUAUUCUUUUGAUAUACUC 22

6685 25565

CFTR- IntronlO- - UGCCUUAUUCUUUUGAUAUACUC 23

6686 25566

CFTR- IntronlO- - AUGCCUUAUUCUUUUGAUAUACUC 24

6687 25567

CFTR- IntronlO- - CCGUAGUCCCAGCUACUC 18

6688 25568

CFTR- IntronlO- - CCCGUAGUCCCAGCUACUC 19

6689 25569

CFTR-

- GCCCGUAGUCCCAGCUACUC 20

lntronlO-687 19573

CFTR- IntronlO- - UGCCCGUAGUCCCAGCUACUC 21

6690 25570

CFTR- IntronlO- - GUGCCCGUAGUCCCAGCUACUC 22

6691 25571

CFTR- IntronlO- - GGUGCCCGUAGUCCCAGCUACUC 23

6692 25572

CFTR- IntronlO- - GGGUGCCCGUAGUCCCAGCUACUC 24

6693 25573

CFTR- IntronlO- - CUUGGACUUCCCAGCCUC 18

6694 25574

1065

5535.1 CFTR- IntronlO- - UCUUGGACUUCCCAGCCUC 19

6695 25575

CFTR- IntronlO- - AUCUUGGACUUCCCAGCCUC 20

6696 25576

CFTR- IntronlO- - GAUCUUGGACUUCCCAGCCUC 21

6697 25577

CFTR- IntronlO- - UGAUCUUGGACUUCCCAGCCUC 22

6698 25578

CFTR- IntronlO- - UUGAUCUUGGACUUCCCAGCCUC 23

6699 25579

CFTR- IntronlO- - CUUGAUCUUGGACUUCCCAGCCUC 24

6700 25580

CFTR- IntronlO- - CACUGCAACCUCUGCCUC 18

6701 25581

CFTR- IntronlO- - UCACUGCAACCUCUGCCUC 19

6702 25582

CFTR- IntronlO- - CUCACUGCAACCUCUGCCUC 20

6703 25583

CFTR- IntronlO- - GCUCACUGCAACCUCUGCCUC 21

6704 25584

CFTR- IntronlO- - GGCUCACUGCAACCUCUGCCUC 22

6705 25585

CFTR- IntronlO- - CGGCUCACUGCAACCUCUGCCUC 23

6706 25586

CFTR- IntronlO- - UCGGCUCACUGCAACCUCUGCCUC 24

6707 25587

CFTR- IntronlO- - AAAAAGUUUAGUGGUCUC 18

6708 25588

1066

5535.1 CFTR- IntronlO- - GAAAAAGUUUAGUGGUCUC 19

6709 25589

CFTR- IntronlO- - AGAAAAAGUUUAGUGGUCUC 20

6710 25590

CFTR- IntronlO- - GAGAAAAAGUUUAGUGGUCUC 21

6711 25591

CFTR- IntronlO- - UGAGAAAAAGUUUAGUGGUCUC 22

6712 25592

CFTR- IntronlO- - GUGAGAAAAAGUUUAGUGGUCUC 23

6713 25593

CFTR- IntronlO- - UGUGAGAAAAAGUUUAGUGGUCUC 24

6714 25594

CFTR- IntronlO- - AGGUGAAUUGCUUGAGUC 18

6715 25595

CFTR- IntronlO- - CAGGUGAAUUGCUUGAGUC 19

6716 25596

CFTR- IntronlO- - GCAGGUGAAUUGCUUGAGUC 20

6717 25597

CFTR- IntronlO- - GGCAGGUGAAUUGCUUGAGUC 21

6718 25598

CFTR- IntronlO- - AGGCAGGUGAAUUGCUUGAGUC 22

6719 25599

CFTR- IntronlO- - GAGGCAGGUGAAUUGCUUGAGUC 23

6720 25600

CFTR- IntronlO- - AGAGGCAGGUGAAUUGCUUGAGUC 24

6721 25601

CFTR- IntronlO- - UAUGUAUAUAUGUGUGUC 18

6722 25602

1067

5535.1 CFTR- IntronlO- - GUAUGUAUAUAUGUGUGUC 19

6723 25603

CFTR- IntronlO- - UGUAUGUAUAUAUGUGUGUC 20

1242 20127

CFTR- IntronlO- - AUGUAUGUAUAUAUGUGUGUC 21

6724 25604

CFTR- IntronlO- - UAUGUAUGUAUAUAUGUGUGUC 22

6725 25605

CFTR- IntronlO- - AUAUGUAUGUAUAUAUGUGUGUC 23

6726 25606

CFTR- IntronlO- - CAUAUGUAUGUAUAUAUGUGUGUC 24

6727 25607

CFTR- IntronlO- - GACCAAAACUUUAUUGUC 18

6728 25608

CFTR- IntronlO- - GGACCAAAACUUUAUUGUC 19

6729 25609

CFTR-

- AGGACCAAAACUUUAUUGUC 20

Intron 10-440 19326

CFTR- IntronlO- - AAGGACCAAAACUUUAUUGUC 21

6730 25610

CFTR- IntronlO- - AAAGG ACCAAAACU UUAUUGUC 22

6731 25611

CFTR- IntronlO- - AAAAGGACCAAAACUUUAUUGUC 23

6732 25612

CFTR- IntronlO- - CAAAAGGACCAAAACUUUAUUGUC 24

6733 25613

CFTR- IntronlO- - CAUUAUAACACUGCUUUC 18

6734 25614

CFTR-

- UCAUUAUAACACUGCUUUC 19

IntronlO- 25615

1068

5535.1 6735

CFTR- IntronlO- - UUCAUUAUAACACUGCUUUC 20

1247 20132

CFTR- IntronlO- - CUUCAUUAUAACACUGCUUUC 21

6736 25616

CFTR- IntronlO- - UCUUCAUUAUAACACUGCUUUC 22

6737 25617

CFTR- IntronlO- - CUCUUCAUUAUAACACUGCUUUC 23

6738 25618

CFTR- IntronlO- - GCUCUUCAUUAUAACACUGCUUUC 24

6739 25619

CFTR- IntronlO- - AUGUACAAGUCUAGUUUC 18

6740 25620

CFTR- IntronlO- - GAUGUACAAGUCUAGUUUC 19

6741 25621

CFTR- IntronlO- - GGAUGUACAAGUCUAGUUUC 20

6742 25622

CFTR- IntronlO- - UGGAUGUACAAGUCUAGUUUC 21

6743 25623

CFTR- IntronlO- - UUGGAUGUACAAGUCUAGUUUC 22

6744 25624

CFTR- IntronlO- - GUUGGAUGUACAAGUCUAGUUUC 23

6745 25625

CFTR- IntronlO- - AGUUGGAUGUACAAGUCUAGUUUC 24

6746 25626

CFTR- IntronlO- - GGAAAAU U U AACAU U U U C 18

6747 25627

CFTR-

- GGGAAAAU U U AACAU U U U C 19

IntronlO- 25628

1069

5535.1 6748

CFTR- IntronlO- - AGGG AAAAU U U AACAU U U U C 20

6749 25629

CFTR- IntronlO- - AAGGG AAAAU U U AACAU U U U C 21

6750 25630

CFTR- IntronlO- - U AAGGG AAAAU U U AACAU U U U C 22

6751 25631

CFTR- IntronlO- - CU AAGGG AAAAU U U AACAU U U U C 23

6752 25632

CFTR- IntronlO- - CCU AAGGG AAAAU U U AACAU U U U C 24

6753 25633

CFTR- IntronlO- - UUCCAUUACAUUGUUUUC 18

6754 25634

CFTR- IntronlO- - UUUCCAUUACAUUGUUUUC 19

6755 25635

CFTR- IntronlO- - GUUUCCAUUACAUUGUUUUC 20

6756 25636

CFTR- IntronlO- - UGUUUCCAUUACAUUGUUUUC 21

6757 25637

CFTR- IntronlO- - GUGUUUCCAUUACAUUGUUUUC 22

6758 25638

CFTR- IntronlO- - AGUGUUUCCAUUACAUUGUUUUC 23

6759 25639

CFTR- IntronlO- - UAGUGUUUCCAUUACAUUGUUUUC 24

6760 25640

CFTR- IntronlO- - AU U AAAAU AUAUAAAAAG 18

6761 25641

CFTR-

- AAU U AAAAU AUAUAAAAAG 19

IntronlO- 25642

1070

5535.1 6762

CFTR- IntronlO- - AAAU U A A A A U A U A U A A A A AG 20

6763 25643

CFTR- IntronlO- - AAAAU U A A A A U A U A U A AAA AG 21

6764 25644

CFTR- IntronlO- - GAAAAU U AAAAU AUAUAAAAAG 22

6765 25645

CFTR- IntronlO- - UGAAAAUUAAAAUAUAUAAAAAG 23

6766 25646

CFTR- IntronlO- - AUGAAAAUUAAAAUAUAUAAAAAG 24

6767 25647

CFTR- IntronlO- - AGAGAGGAAGGAAGAAAG 18

6768 25648

CFTR- IntronlO- - AAGAGAGGAAGGAAGAAAG 19

6769 25649

CFTR- IntronlO- - AAAGAGAGGAAGGAAGAAAG 20

6770 25650

CFTR- IntronlO- - GAAAGAGAGGAAGG AAG AAAG 21

6771 25651

CFTR- IntronlO- - AG AAAG AG AG G AAG G AAG AAAG 22

6772 25652

CFTR- IntronlO- - AAGAAAGAGAGGAAGGAAGAAAG 23

6773 25653

CFTR- IntronlO- - A AAG AAAG AG AG G AAG G AAG AAAG 24

6774 25654

CFTR- IntronlO- - GGAAGGAAGGAAGGAAAG 18

6775 25655

CFTR-

- AGGAAGGAAGGAAGG AAAG 19

IntronlO- 25656

1071

5535.1 6776

CFTR- IntronlO- - GAGGAAGGAAGGAAGGAAAG 20

6777 25657

CFTR- IntronlO- - GG AG G AAG G AAG G AAG G AAAG 21

6778 25658

CFTR- IntronlO- - AGGAGGAAGGAAGGAAGGAAAG 22

6779 25659

CFTR- IntronlO- - UAGGAGGAAGGAAGGAAGGAAAG 23

6780 25660

CFTR- IntronlO- - GUAGGAGGAAGGAAGGAAGGAAAG 24

6781 25661

CFTR- IntronlO- - AACCCAACUGAUGUCAAG 18

6782 25662

CFTR- IntronlO- - GAACCCAACUGAUGUCAAG 19

6783 25663

CFTR- IntronlO- - GGAACCCAACUGAUGUCAAG 20

6784 25664

CFTR- IntronlO- - CGGAACCCAACUGAUGUCAAG 21

6785 25665

CFTR- IntronlO- - CCGGAACCCAACUGAUGUCAAG 22

6786 25666

CFTR- IntronlO- - CCCGGAACCCAACUGAUGUCAAG 23

6787 25667

CFTR- IntronlO- - UCCCGGAACCCAACUGAUGUCAAG 24

6788 25668

CFTR- IntronlO- - UCACCUGAGCCUGAGAAG 18

6789 25669

CFTR-

- AUCACCUGAGCCUGAGAAG 19

IntronlO- 25670

1072

5535.1 6790

CFTR-

- GAUCACCUGAGCCUGAGAAG 20

lntronlO-692 19578

CFTR- IntronlO- - GGAUCACCUGAGCCUGAGAAG 21

6791 25671

CFTR- IntronlO- - AGGAUCACCUGAGCCUGAGAAG 22

6792 25672

CFTR- IntronlO- - GAGGAUCACCUGAGCCUGAGAAG 23

6793 25673

CFTR- IntronlO- - GGAGGAUCACCUGAGCCUGAGAAG 24

6794 25674

CFTR- IntronlO- - AAUGAGGAAGAAAGGAAG 18

6795 25675

CFTR- IntronlO- - AAAUGAGGAAGAAAGGAAG 19

6796 25676

CFTR- IntronlO- - GAAAUGAGGAAGAAAGGAAG 20

6797 25677

CFTR- IntronlO- - G G AAA U G AG G A AG A A AG G A AG 21

6798 25678

CFTR- IntronlO- - AG G A A A U G AG G A AG A A AG G A AG 22

6799 25679

CFTR- IntronlO- - AAGGAAAUGAGGAAGAAAGGAAG 23

6800 25680

CFTR- IntronlO- - GAAGGAAAUGAGGAAGAAAGGAAG 24

6801 25681

CFTR- IntronlO- - AG U CU AG U U U CAAGG AAG 18

6802 25682

CFTR- IntronlO- - AAG U CU AG U U U CAAGG AAG 19

6803 25683

1073

5535.1 CFTR-

- CAAG U C U AG U U U CAAGGAAG 20

Intron 10-449 19335

CFTR- IntronlO- - A C A AG UCUAGUUU C A AG G A AG 21

6804 25684

CFTR- IntronlO- - UACAAG U CU AG U U U CAAGGAAG 22

6805 25685

CFTR- IntronlO- - GUACAAGUCUAGUUUCAAGGAAG 23

6806 25686

CFTR- IntronlO- - UGUACAAGUCUAGUUUCAAGGAAG 24

6807 25687

CFTR- IntronlO- - GGGGCUGGUAGUGUGAAG 18

6808 25688

CFTR- IntronlO- - GGGGGCUGGUAGUGUGAAG 19

6809 25689

CFTR- IntronlO- - AGGGGGCUGGUAGUGUGAAG 20

6810 25690

CFTR- IntronlO- - GAGGGGGCUGGUAGUGUGAAG 21

6811 25691

CFTR- IntronlO- - AGAGGGGGCUGGUAGUGUGAAG 22

6812 25692

CFTR- IntronlO- - AAGAGGGGGCUGGUAGUGUGAAG 23

6813 25693

CFTR- IntronlO- - GAAGAGGGGGCUGGUAGUGUGAAG 24

6814 25694

CFTR- IntronlO- - GAAAU U AG AAAG AAU AAG 18

6815 25695

CFTR- IntronlO- - U G AAA U U AG A A AG A A U A AG 19

6816 25696

CFTR-

- AUGAAAUUAGAAAGAAUAAG 20

IntronlO- 20139

1074

5535.1 1254

CFTR- IntronlO- - AAUGAAAUUAGAAAGAAUAAG 21

6817 25697

CFTR- IntronlO- - GAAUGAAAUUAGAAAGAAUAAG 22

6818 25698

CFTR- IntronlO- - AGAAUGAAAUUAGAAAGAAUAAG 23

6819 25699

CFTR- IntronlO- - CAGAAUGAAAUUAGAAAGAAUAAG 24

6820 25700

CFTR- IntronlO- - AUAGGAUUAAUGGAUAAG 18

6821 25701

CFTR- IntronlO- - AAUAGGAUUAAUGGAUAAG 19

6822 25702

CFTR- IntronlO- - CAAUAGGAUUAAUGGAUAAG 20

6823 25703

CFTR- IntronlO- - CCAAUAGGAUUAAUGGAUAAG 21

6824 25704

CFTR- IntronlO- - UCCAAUAGGAUUAAUGGAUAAG 22

6825 25705

CFTR- IntronlO- - AUCCAAUAGGAUUAAUGGAUAAG 23

6826 25706

CFTR- IntronlO- - GAUCCAAUAGGAUUAAUGGAUAAG 24

6827 25707

CFTR- IntronlO- - GGAAAGAGGGUUGAUAAG 18

6828 25708

CFTR- IntronlO- - AGGAAAGAGGGUUGAUAAG 19

6829 25709

CFTR-

- A AG G A A AG AGGGUUGAUAAG 20

IntronlO- 25710

1075

5535.1 6830

CFTR- IntronlO- - AAAGGAAAGAGGGUUGAUAAG 21

6831 25711

CFTR- IntronlO- - UAAAGGAAAGAGGGUUGAUAAG 22

6832 25712

CFTR- IntronlO- - CUAAAGGAAAGAGGGUUGAUAAG 23

6833 25713

CFTR- IntronlO- - UCUAAAGGAAAGAGGGUUGAUAAG 24

6834 25714

CFTR- IntronlO- - UAUUUAUCAAUAUCUAAG 18

6835 25715

CFTR- IntronlO- - UUAUUUAUCAAUAUCUAAG 19

6836 25716

CFTR- IntronlO- - AUUAUUUAUCAAUAUCUAAG 20

6837 25717

CFTR- IntronlO- - AAUUAUUUAUCAAUAUCUAAG 21

6838 25718

CFTR- IntronlO- - CAAU U AU U U AU CAAU AU CU AAG 22

6839 25719

CFTR- IntronlO- - GCAAUUAUUUAUCAAUAUCUAAG 23

6840 25720

CFTR- IntronlO- - GGCAAUUAUUUAUCAAUAUCUAAG 24

6841 25721

CFTR- IntronlO- - GCUCAUUCAUCAAGUAAG 18

6842 25722

CFTR- IntronlO- - UGCUCAUUCAUCAAGUAAG 19

6843 25723

CFTR-

- AUGCUCAUUCAUCAAGUAAG 20

IntronlO- 25724

1076

5535.1 6844

CFTR- IntronlO- - AAUGCUCAUUCAUCAAGUAAG 21

6845 25725

CFTR- IntronlO- - AAAUGCUCAUUCAUCAAGUAAG 22

6846 25726

CFTR- IntronlO- - CAAAUGCUCAUUCAUCAAGUAAG 23

6847 25727

CFTR- IntronlO- - UCAAAUGCUCAUUCAUCAAGUAAG 24

6848 25728

CFTR- IntronlO- - A AG AAG G AAG G AAG UAAG 18

6849 25729

CFTR- IntronlO- - A A AG A AG G A AG G A AG U A AG 19

6850 25730

CFTR-

- G A AAG AAG G AAG G AAG UAAG 20

lntronlO-693 19579

CFTR- IntronlO- - G G A AAG AAG G AAG G AAG UAAG 21

6851 25731

CFTR- IntronlO- - AGGAAAGAAGGAAGG AAG UAAG 22

6852 25732

CFTR- IntronlO- - AAGGAAAGAAGGAAGGAAGUAAG 23

6853 25733

CFTR- IntronlO- - GAAGGAAAGAAGGAAGGAAGUAAG 24

6854 25734

CFTR- IntronlO- - UGCCAUGUGAGAACACAG 18

6855 25735

CFTR- IntronlO- - CUGCCAUGUGAGAACACAG 19

6856 25736

CFTR- IntronlO- - UCUGCCAUGUGAGAACACAG 20

6857 25737

1077

5535.1 CFTR- IntronlO- - UUCUGCCAUGUGAGAACACAG 21

6858 25738

CFTR- IntronlO- - UUUCUGCCAUGUGAGAACACAG 22

6859 25739

CFTR- IntronlO- - CUUUCUGCCAUGUGAGAACACAG 23

6860 25740

CFTR- IntronlO- - CCUUUCUGCCAUGUGAGAACACAG 24

6861 25741

CFTR- IntronlO- - AUUUCAACUUAUACACAG 18

6862 25742

CFTR- IntronlO- - CAU U U CAACU U AU ACACAG 19

6863 25743

CFTR- IntronlO- - UCAUUUCAACUUAUACACAG 20

6864 25744

CFTR- IntronlO- - AUCAUUUCAACUUAUACACAG 21

6865 25745

CFTR- IntronlO- - UAUCAUUUCAACUUAUACACAG 22

6866 25746

CFTR- IntronlO- - AUAUCAUUUCAACUUAUACACAG 23

6867 25747

CFTR- IntronlO- - AAU AU CAU U U CAACU UAU ACACAG 24

6868 25748

CFTR- IntronlO- - CUGUUGUCUGCAUCACAG 18

6869 25749

CFTR- IntronlO- - UCUGUUGUCUGCAUCACAG 19

6870 25750

CFTR- IntronlO- - UUCUGUUGUCUGCAUCACAG 20

6871 25751

1078

5535.1 CFTR- IntronlO- - CUUCUGUUGUCUGCAUCACAG 21

6872 25752

CFTR- IntronlO- - CCUUCUGUUGUCUGCAUCACAG 22

6873 25753

CFTR- IntronlO- - UCCUUCUGUUGUCUGCAUCACAG 23

6874 25754

CFTR- IntronlO- - GUCCUUCUGUUGUCUGCAUCACAG 24

6875 25755

CFTR- IntronlO- - GAGUCUUCCAAGUAGCAG 18

6876 25756

CFTR- IntronlO- - AG AG U CU U CCAAG U AG CAG 19

6877 25757

CFTR- IntronlO- - AAG AG U CU U CCAAG U AG CAG 20

6878 25758

CFTR- IntronlO- - GAAGAG UCUU CCAAG U AG CAG 21

6879 25759

CFTR- IntronlO- - GGAAGAGUCUUCCAAGUAGCAG 22

6880 25760

CFTR- IntronlO- - GGGAAGAGUCUUCCAAGUAGCAG 23

6881 25761

CFTR- IntronlO- - UGGGAAGAGUCUUCCAAGUAGCAG 24

6882 25762

CFTR- IntronlO- - CCAAAACU U U AU UG U CAG 18

6883 25763

CFTR- IntronlO- - ACCAAAACUUUAUUGUCAG 19

6884 25764

CFTR- IntronlO- - GACCAAAACUUUAUUGUCAG 20

6885 25765

1079

5535.1 CFTR- IntronlO- - GGACCAAAACUUUAUUGUCAG 21

6886 25766

CFTR- IntronlO- - AGGACCAAAACUUUAUUGUCAG 22

6887 25767

CFTR- IntronlO- - AAGGACCAAAACUUUAUUGUCAG 23

6888 25768

CFTR- IntronlO- - AAAGGACCAAAACUUUAUUGUCAG 24

6889 25769

CFTR- IntronlO- - CAAGUG CAAAGCU U U CAG 18

6890 25770

CFTR- IntronlO- - G C A AG U G C A A AG C U U U C AG 19

6891 25771

CFTR- IntronlO- - AG C A AG U G C A A AG C U U U C AG 20

6892 25772

CFTR- IntronlO- - A AG CAAGUG C A A AG C U U U C AG 21

6893 25773

CFTR- IntronlO- - G A AG C A AG U G C A A AG C U U U C AG 22

6894 25774

CFTR- IntronlO- - U G A AG C A AG U G C A A AG C U U U C AG 23

6895 25775

CFTR- IntronlO- - GUGAAGCAAGUG C A A AG C U U U C AG 24

6896 25776

CFTR- IntronlO- - AAACAGAAAAAGAAAGAG 18

6897 25777

CFTR- IntronlO- - CAAACAGAAAAAGAAAGAG 19

6898 25778

CFTR- IntronlO- - ACAAACAGAAAAAGAAAGAG 20

1269 20154

1080

5535.1 CFTR- IntronlO- - GACAAACAGAAAAAGAAAGAG 21

6899 25779

CFTR- IntronlO- - AGACAAACAGAAAAAGAAAGAG 22

6900 25780

CFTR- IntronlO- - AAGACAAACAGAAAAAGAAAGAG 23

6901 25781

CFTR- IntronlO- - UAAGACAAACAGAAAAAGAAAGAG 24

6902 25782

CFTR- IntronlO- - AUUUUUGUAUUUUUAGUAGAG 21

6903 25783

CFTR- IntronlO- - AAUUUUUGUAUUUUUAGUAGAG 22

6904 25784

CFTR- IntronlO- - UAAUUUUUGUAUUUUUAGUAGAG 23

6905 25785

CFTR- IntronlO- - CUAAUUUUUGUAUUUUUAGUAGAG 24

6906 25786

CFTR- IntronlO- - GAAAGAAUCAAAUUAGAG 18

6907 25787

CFTR- IntronlO- - UGAAAGAAUCAAAUUAGAG 19

6908 25788

CFTR- IntronlO- - A U G A A AG A A U C A A A U U AG AG 20

6909 25789

CFTR- IntronlO- - CAUGAAAGAAUCAAAUUAGAG 21

6910 25790

CFTR- IntronlO- - ACAUGAAAGAAUCAAAUUAGAG 22

6911 25791

CFTR- IntronlO- - GACAUGAAAGAAUCAAAUUAGAG 23

6912 25792

1081

5535.1 CFTR- IntronlO- - AGACAUGAAAGAAUCAAAUUAGAG 24

6913 25793

CFTR- IntronlO- - AACAAAGACUUGCAGGAG 18

6914 25794

CFTR- IntronlO- - GAACAAAGACUUGCAGGAG 19

6915 25795

CFTR- IntronlO- - UGAACAAAGACUUGCAGGAG 20

6916 25796

CFTR- IntronlO- - UUGAACAAAGACUUGCAGGAG 21

6917 25797

CFTR- IntronlO- - UUUGAACAAAGACUUGCAGGAG 22

6918 25798

CFTR- IntronlO- - AUUUGAACAAAGACUUGCAGGAG 23

6919 25799

CFTR- IntronlO- - CAU U U G AAC AAAG AC U U G CAG GAG 24

6920 25800

CFTR- IntronlO- - AUCAAUAUCUAAGAUGAG 18

6921 25801

CFTR- IntronlO- - UAUCAAUAUCUAAGAUGAG 19

6922 25802

CFTR- IntronlO- - UU AUCAAUAUCUAAGAUGAG 20

6923 25803

CFTR- IntronlO- - UU UAUCAAUAUCUAAGAUGAG 21

6924 25804

CFTR- IntronlO- - AUUUAUCAAUAUCUAAGAUGAG 22

6925 25805

CFTR- IntronlO- - UAUUUAUCAAUAUCUAAGAUGAG 23

6926 25806

1082

5535.1 CFTR- IntronlO- - UUAUUUAUCAAUAUCUAAGAUGAG 24

6927 25807

CFTR- IntronlO- - GCUACUUGGGAGGCUGAG 18

6928 25808

CFTR- IntronlO- - AGCUACUUGGGAGGCUGAG 19

6929 25809

CFTR- IntronlO- - CAGCUACUUGGGAGGCUGAG 20

6930 25810

CFTR- IntronlO- - CCAGCUACUUGGGAGGCUGAG 21

6931 25811

CFTR- IntronlO- - CCCAGCUACUUGGGAGGCUGAG 22

6932 25812

CFTR- IntronlO- - UCCCAGCUACUUGGGAGGCUGAG 23

6933 25813

CFTR- IntronlO- - GUCCCAGCUACUUGGGAGGCUGAG 24

6934 25814

CFTR- IntronlO- - GGCAGAACUUGCAGUGAG 18

6935 25815

CFTR- IntronlO- - AGGCAGAACUUGCAGUGAG 19

6936 25816

CFTR- IntronlO- - GAGGCAGAACUUGCAGUGAG 20

6937 25817

CFTR- IntronlO- - GGAGGCAGAACUUGCAGUGAG 21

6938 25818

CFTR- IntronlO- - AGGAGGCAGAACUUGCAGUGAG 22

6939 25819

CFTR- IntronlO- - CAGGAGGCAGAACUUGCAGUGAG 23

6940 25820

1083

5535.1 CFTR- IntronlO- - CCAGGAGGCAGAACUUGCAGUGAG 24

6941 25821

CFTR- IntronlO- - UUUUUUUUUUUUUUUGAG 18

6942 25822

CFTR- IntronlO- - UUUUUUUUUUUUUUUUGAG 19

6943 25823

CFTR- IntronlO- - UUUUUUUUUUUUUUUUUGAG 20

6944 25824

CFTR- IntronlO- - UUUUUUUUUUUUUUUUUUGAG 21

6945 25825

CFTR- IntronlO- - UUUUUUUUUUUUUUUUUUUGAG 22

6946 25826

CFTR- IntronlO- - UUUUUUUUUUUUUUUUUUUUGAG 23

6947 25827

CFTR- IntronlO- - UUUUUUUUUUUUUUUUUUUUUGAG 24

6948 25828

CFTR- IntronlO- - G C U U U U A A A AC A A A A U AG 18

6949 25829

CFTR- IntronlO- - AGCU U U U AAAACAAAAU AG 19

6950 25830

CFTR- IntronlO- - CAG CU U U U AAAACAAAAU AG 20

6951 25831

CFTR- IntronlO- - ACAG CU U U U AAAACAAAAU AG 21

6952 25832

CFTR- IntronlO- - AACAGCU U U U AAAACAAAAU AG 22

6953 25833

CFTR- IntronlO- - AAACAG CU U U U AAAACAAAAU AG 23

6954 25834

1084

5535.1 CFTR- IntronlO- - G AAACAGCU U U U AAAACAAAAU AG 24

6955 25835

CFTR- IntronlO- - ACUUAAUGAAAGCAAUAG 18

6956 25836

CFTR- IntronlO- - GACUUAAUGAAAGCAAUAG 19

6957 25837

CFTR- IntronlO- - UGACUUAAUGAAAGCAAUAG 20

6958 25838

CFTR- IntronlO- - GUGACUUAAUGAAAGCAAUAG 21

6959 25839

CFTR- IntronlO- - CGUGACUUAAUGAAAGCAAUAG 22

6960 25840

CFTR- IntronlO- - UCGUGACUUAAUGAAAGCAAUAG 23

6961 25841

CFTR- IntronlO- - CUCGUGACUUAAUGAAAGCAAUAG 24

6962 25842

CFTR- IntronlO- - U AAAAAAU U AU ACU AU AG 18

6963 25843

CFTR- IntronlO- - U U AAAAAAU U AU ACU AU AG 19

6964 25844

CFTR- IntronlO- - AU U AAAAAAU U AU ACU AU AG 20

6965 25845

CFTR- IntronlO- - UAUUAAAAAAUUAUACUAUAG 21

6966 25846

CFTR- IntronlO- - CUAUUAAAAAAUUAUACUAUAG 22

6967 25847

CFTR- IntronlO- - ACUAUUAAAAAAUUAUACUAUAG 23

6968 25848

1085

5535.1 CFTR- IntronlO- - CACUAUUAAAAAAUUAUACUAUAG 24

6969 25849

CFTR- IntronlO- - GUAGUGGAAGUAGUAUAG 18

6970 25850

CFTR- IntronlO- - AGUAGUGGAAGUAGUAUAG 19

6971 25851

CFTR- IntronlO- - UAGUAGUGGAAGUAGUAUAG 20

6972 25852

CFTR- IntronlO- - GUAGUAGUGGAAGUAGUAUAG 21

6973 25853

CFTR- IntronlO- - GGUAGUAGUGGAAGUAGUAUAG 22

6974 25854

CFTR- IntronlO- - AGGUAGUAGUGGAAGUAGUAUAG 23

6975 25855

CFTR- IntronlO- - CAGGUAGUAGUGGAAGUAGUAUAG 24

6976 25856

CFTR- IntronlO- - CCUCACCCUCCCAAGUAG 18

6977 25857

CFTR- IntronlO- - GCCUCACCCUCCCAAGUAG 19

6978 25858

CFTR- IntronlO- - UGCCUCACCCUCCCAAGUAG 20

6979 25859

CFTR- IntronlO- - CUGCCUCACCCUCCCAAGUAG 21

6980 25860

CFTR- IntronlO- - CCUGCCUCACCCUCCCAAGUAG 22

6981 25861

CFTR- IntronlO- - UCCUGCCUCACCCUCCCAAGUAG 23

6982 25862

1086

5535.1 CFTR- IntronlO- - CUCCUGCCUCACCCUCCCAAGUAG 24

6983 25863

CFTR- IntronlO- - GCCUCAGCCUCCCAAGUAG 19

6984 25864

CFTR- IntronlO- - UGCCUCAGCCUCCCAAGUAG 20

6985 25865

CFTR- IntronlO- - CUGCCUCAGCCUCCCAAGUAG 21

6986 25866

CFTR- IntronlO- - CCUGCCUCAGCCUCCCAAGUAG 22

6987 25867

CFTR- IntronlO- - UCCUGCCUCAGCCUCCCAAGUAG 23

6988 25868

CFTR- IntronlO- - CUCCUGCCUCAGCCUCCCAAGUAG 24

6989 25869

CFTR- IntronlO- - GAGGAAGAAAGGAAGUAG 18

6990 25870

CFTR- IntronlO- - UGAGGAAGAAAGGAAGUAG 19

6991 25871

CFTR- IntronlO- - AUGAGGAAGAAAGGAAGUAG 20

6992 25872

CFTR- IntronlO- - AAUGAGGAAGAAAGGAAGUAG 21

6993 25873

CFTR- IntronlO- - AAAUGAGGAAGAAAGGAAGUAG 22

6994 25874

CFTR- IntronlO- - GAAAUGAGGAAGAAAGGAAGUAG 23

6995 25875

CFTR- IntronlO- - GGAAAUGAGGAAGAAAGGAAGUAG 24

6996 25876

1087

5535.1 CFTR- IntronlO- - GCUUGAUCCAGGUAGUAG 18

6997 25877

CFTR- IntronlO- - GGCUUGAUCCAGGUAGUAG 19

6998 25878

CFTR-

- UGGCUUGAUCCAGGUAGUAG 20

lntronlO-461 19347

CFTR- IntronlO- - GUGGCUUGAUCCAGGUAGUAG 21

6999 25879

CFTR- IntronlO- - GGUGGCUUGAUCCAGGUAGUAG 22

7000 25880

CFTR- IntronlO- - UGGUGGCUUGAUCCAGGUAGUAG 23

7001 25881

CFTR- IntronlO- - AUGGUGGCUUGAUCCAGGUAGUAG 24

7002 25882

CFTR- IntronlO- - CUAUGAAGGCAGAGUUAG 18

7003 25883

CFTR- IntronlO- - GCUAUGAAGGCAGAGUUAG 19

7004 25884

CFTR-

- AGCUAUGAAGGCAGAGUUAG 20

lntronlO-464 19350

CFTR- IntronlO- - CAGCUAUGAAGGCAGAGUUAG 21

7005 25885

CFTR- IntronlO- - GCAGCUAUGAAGGCAGAGUUAG 22

7006 25886

CFTR- IntronlO- - AGCAGCUAUGAAGGCAGAGUUAG 23

7007 25887

CFTR- IntronlO- - AAGCAGCUAUGAAGGCAGAGUUAG 24

7008 25888

CFTR- IntronlO- - GGGGUUUCACCGUUUUAG 18

7009 25889

1088

5535.1 CFTR- IntronlO- - CGGGGUUUCACCGUUUUAG 19

7010 25890

CFTR- IntronlO- - ACGGGGUUUCACCGUUUUAG 20

7011 25891

CFTR- IntronlO- - GACGGGGUUUCACCGUUUUAG 21

7012 25892

CFTR- IntronlO- - AGACGGGGUUUCACCGUUUUAG 22

7013 25893

CFTR- IntronlO- - G AG ACGGGG U U U CACCG U U U U AG 23

7014 25894

CFTR- IntronlO- - AGAGACGGGGUUUCACCGUUUUAG 24

7015 25895

CFTR- IntronlO- - UAAUUUUUGUAUUUUUAG 18

7016 25896

CFTR- IntronlO- - CUAAUUUUUGUAUUUUUAG 19

7017 25897

CFTR- IntronlO- - GCUAAUUUUUGUAUUUUUAG 20

7018 25898

CFTR- IntronlO- - AGCUAAUUUUUGUAUUUUUAG 21

7019 25899

CFTR- IntronlO- - CAGCUAAUUUUUGUAUUUUUAG 22

7020 25900

CFTR- IntronlO- - UCAGCUAAUUUUUGUAUUUUUAG 23

7021 25901

CFTR- IntronlO- - CUCAGCUAAUUUUUGUAUUUUUAG 24

7022 25902

CFTR- IntronlO- - CGGCUAAUUUUUUGUAUUUUUAG 23

7023 25903

1089

5535.1 CFTR- IntronlO- - CCGGCUAAUUUUUUGUAUUUUUAG 24

7024 25904

CFTR- IntronlO- - UCAGAGAAGUAAUCGGCG 18

7025 25905

CFTR- IntronlO- - GUCAGAGAAGUAAUCGGCG 19

7026 25906

CFTR- IntronlO- - UGUCAGAGAAGUAAUCGGCG 20

7027 25907

CFTR- IntronlO- - CUGUCAGAGAAGUAAUCGGCG 21

7028 25908

CFTR- IntronlO- - ACUGUCAGAGAAGUAAUCGGCG 22

7029 25909

CFTR- IntronlO- - UACUGUCAGAGAAGUAAUCGGCG 23

7030 25910

CFTR- IntronlO- - AUACUGUCAGAGAAGUAAUCGGCG 24

7031 25911

CFTR- IntronlO- - UUCUGUAGGGAGACAAGG 18

7032 25912

CFTR- IntronlO- - AUUCUGUAGGGAGACAAGG 19

7033 25913

CFTR- IntronlO- - UAUUCUGUAGGGAGACAAGG 20

7034 25914

CFTR- IntronlO- - CUAUUCUGUAGGGAGACAAGG 21

7035 25915

CFTR- IntronlO- - GCUAUUCUGUAGGGAGACAAGG 22

7036 25916

CFTR- IntronlO- - GGCUAUUCUGUAGGGAGACAAGG 23

7037 25917

1090

5535.1 CFTR- IntronlO- - AGGCUAUUCUGUAGGGAGACAAGG 24

7038 25918

CFTR- IntronlO- - ACAAGUCUAGUUUCAAGG 18

7039 25919

CFTR- IntronlO- - UACAAGUCUAGUUUCAAGG 19

7040 25920

CFTR- IntronlO- - GUACAAGUCUAGUUUCAAGG 20

7041 25921

CFTR- IntronlO- - UGUACAAGUCUAGUUUCAAGG 21

7042 25922

CFTR- IntronlO- - AUGUACAAGUCUAGUUUCAAGG 22

7043 25923

CFTR- IntronlO- - GAUGUACAAGUCUAGUUUCAAGG 23

7044 25924

CFTR- IntronlO- - GGAUGUACAAGUCUAGUUUCAAGG 24

7045 25925

CFTR- IntronlO- - GGAAGGAAGGAAAGAAGG 18

7046 25926

CFTR- IntronlO- - AG G AAG G AAG G AAAG AAG G 19

7047 25927

CFTR- IntronlO- - AAGGAAGGAAGGAAAGAAGG 20

7048 25928

CFTR- IntronlO- - G AAG G AAG G AAG G AAAG AAG G 21

7049 25929

CFTR- IntronlO- - GGAAGGAAGGAAGGAAAGAAGG 22

7050 25930

CFTR- IntronlO- - AG G AAG G AAG G AAG G AAAG AAGG 23

7051 25931

1091

5535.1 CFTR- IntronlO- - GAGGAAGGAAGGAAGGAAAGAAGG 24

7052 25932

CFTR- IntronlO- - AAGUAGGAGGAAGGAAGG 18

7053 25933

CFTR- IntronlO- - GAAGUAGGAGGAAGGAAGG 19

7054 25934

CFTR- IntronlO- - GGAAG U AGG AGG AAGG AAGG 20

7055 25935

CFTR- IntronlO- - AGGAAGUAGGAGGAAGGAAGG 21

7056 25936

CFTR- IntronlO- - AAGGAAGU AGG AGG AAGG AAGG 22

7057 25937

CFTR- IntronlO- - AAAGGAAGUAGGAGGAAGGAAGG 23

7058 25938

CFTR- IntronlO- - GAAAGGAAGUAGGAGGAAGGAAGG 24

7059 25939

CFTR- IntronlO- - A A A AG A A AG AG AG G A AG G 18

7060 25940

CFTR- IntronlO- - AAAAAGAAAGAGAGGAAGG 19

7061 25941

CFTR- IntronlO- - G A A A A AG A A AG AG AG G AAG G 20

7062 25942

CFTR- IntronlO- - AGAAAAAGAAAGAGAGGAAGG 21

7063 25943

CFTR- IntronlO- - CAGAAAAAGAAAGAGAGGAAGG 22

7064 25944

CFTR- IntronlO- - ACAGAAAAAGAAAGAGAGGAAGG 23

7065 25945

1092

5535.1 CFTR- IntronlO- - AAC AG AAAAAG AAAG AG AG G AAG G 24

7066 25946

CFTR- IntronlO- - AAGGAAGUAGGAGGAAGG 18

7067 25947

CFTR- IntronlO- - AAAGGAAGUAGGAGGAAGG 19

7068 25948

CFTR- IntronlO- - GAAAGGAAGUAGGAGGAAGG 20

7069 25949

CFTR- IntronlO- - AGAAAGGAAGUAGGAGGAAGG 21

7070 25950

CFTR- IntronlO- - AAGAAAGGAAGUAGGAGGAAGG 22

7071 25951

CFTR- IntronlO- - GAAGAAAGGAAGUAGGAGGAAGG 23

7072 25952

CFTR- IntronlO- - GGAAGAAAGGAAGUAGGAGGAAGG 24

7073 25953

CFTR- IntronlO- - AGUCUUACUGUCACCAGG 18

7074 25954

CFTR- IntronlO- - GAGUCUUACUGUCACCAGG 19

7075 25955

CFTR- IntronlO- - AGAGUCUUACUGUCACCAGG 20

7076 25956

CFTR- IntronlO- - CAGAGUCUUACUGUCACCAGG 21

7077 25957

CFTR- IntronlO- - ACAGAGUCUUACUGUCACCAGG 22

7078 25958

CFTR- IntronlO- - G ACAG AG UCUUACUGU CACCAGG 23

7079 25959

1093

5535.1 CFTR- IntronlO- - AGACAGAGUCUUACUGUCACCAGG 24

7080 25960

CFTR- IntronlO- - CUUACUCUGUCACCCAGG 18

7081 25961

CFTR- IntronlO- - UCUUACUCUGUCACCCAGG 19

7082 25962

CFTR- IntronlO- - GUCUUACUCUGUCACCCAGG 20

7083 25963

CFTR- IntronlO- - GGUCUUACUCUGUCACCCAGG 21

7084 25964

CFTR- IntronlO- - AGGUCUUACUCUGUCACCCAGG 22

7085 25965

CFTR- IntronlO- - UAGGUCUUACUCUGUCACCCAGG 23

7086 25966

CFTR- IntronlO- - UUAGGUCUUACUCUGUCACCCAGG 24

7087 25967

CFTR- IntronlO- - CUCGCUCUGUCGCCCAGG 18

7088 25968

CFTR- IntronlO- - UCUCGCUCUGUCGCCCAGG 19

7089 25969

CFTR- IntronlO- - GUCUCGCUCUGUCGCCCAGG 20

7090 25970

CFTR- IntronlO- - AGUCUCGCUCUGUCGCCCAGG 21

7091 25971

CFTR- IntronlO- - GAGUCUCGCUCUGUCGCCCAGG 22

7092 25972

CFTR- IntronlO- - GGAGUCUCGCUCUGUCGCCCAGG 23

7093 25973

1094

5535.1 CFTR- IntronlO- - CGGAGUCUCGCUCUGUCGCCCAGG 24

7094 25974

CFTR- IntronlO- - AGGUGAUGGUAUUGCAGG 18

7095 25975

CFTR- IntronlO- - AAGGUGAUGGUAUUGCAGG 19

7096 25976

CFTR- IntronlO- - CAAGGUGAUGGUAUUGCAGG 20

7097 25977

CFTR- IntronlO- - CCAAGGUGAUGGUAUUGCAGG 21

7098 25978

CFTR- IntronlO- - CCCAAGGUGAUGGUAUUGCAGG 22

7099 25979

CFTR- IntronlO- - UCCCAAGGUGAUGGUAUUGCAGG 23

7100 25980

CFTR- IntronlO- - UUCCCAAGGUGAUGGUAUUGCAGG 24

7101 25981

CFTR- IntronlO- - CAGAAAAAGAAAGAGAGG 18

7102 25982

CFTR- IntronlO- - ACAGAAAAAGAAAGAGAGG 19

7103 25983

CFTR- IntronlO- - AACAGAAAAAGAAAGAGAGG 20

7104 25984

CFTR- IntronlO- - AAACAGAAAAAGAAAGAGAGG 21

7105 25985

CFTR- IntronlO- - CAAACAGAAAAAGAAAGAGAGG 22

7106 25986

CFTR- IntronlO- - ACAAACAGAAAAAGAAAGAGAGG 23

7107 25987

1095

5535.1 CFTR- IntronlO- - GACAAACAGAAAAAGAAAGAGAGG 24

7108 25988

CFTR- IntronlO- - UGGCGUGAACCCAGGAGG 18

7109 25989

CFTR- IntronlO- - AUGGCGUGAACCCAGGAGG 19

7110 25990

CFTR- IntronlO- - AAUGGCGUGAACCCAGGAGG 20

7111 25991

CFTR- IntronlO- - GAAUGGCGUGAACCCAGGAGG 21

7112 25992

CFTR- IntronlO- - AGAAUGGCGUGAACCCAGGAGG 22

7113 25993

CFTR- IntronlO- - GAGAAUGGCGUGAACCCAGGAGG 23

7114 25994

CFTR- IntronlO- - GGAGAAUGGCGUGAACCCAGGAGG 24

7115 25995

CFTR- IntronlO- - AAGAAAGGAAGUAGGAGG 18

7116 25996

CFTR- IntronlO- - GAAGAAAGGAAGUAGGAGG 19

7117 25997

CFTR- IntronlO- - GGAAGAAAGGAAGUAGGAGG 20

7118 25998

CFTR- IntronlO- - AGGAAGAAAGGAAGUAGGAGG 21

7119 25999

CFTR- IntronlO- - GAGG AAGAAAGGAAGUAGGAGG 22

7120 26000

CFTR- IntronlO- - UGAGGAAGAAAGGAAGUAGGAGG 23

7121 26001

1096

5535.1 CFTR- IntronlO- - AUGAGGAAGAAAGGAAGUAGGAGG 24

7122 26002

CFTR- IntronlO- - UCCCAGCUACUCGGGAGG 18

7123 26003

CFTR- IntronlO- - GUCCCAGCUACUCGGGAGG 19

7124 26004

CFTR- IntronlO- - AGUCCCAGCUACUCGGGAGG 20

7125 26005

CFTR- IntronlO- - UAGUCCCAGCUACUCGGGAGG 21

7126 26006

CFTR- IntronlO- - GU AGUCCCAGCUACUCGGGAGG 22

7127 26007

CFTR- IntronlO- - CGUAGUCCCAGCUACUCGGGAGG 23

7128 26008

CFTR- IntronlO- - CCGUAGUCCCAGCUACUCGGGAGG 24

7129 26009

CFTR- IntronlO- - AGUAAUCGGCGGUGGAGG 18

7130 26010

CFTR- IntronlO- - AAGUAAUCGGCGGUGGAGG 19

7131 26011

CFTR- IntronlO- - GAAGUAAUCGGCGGUGGAGG 20

7132 26012

CFTR- IntronlO- - AGAAGUAAUCGGCGGUGGAGG 21

7133 26013

CFTR- IntronlO- - GAGAAGUAAUCGGCGGUGGAGG 22

7134 26014

CFTR- IntronlO- - AGAGAAGUAAUCGGCGGUGGAGG 23

7135 26015

1097

5535.1 CFTR- IntronlO- - CAGAGAAGUAAUCGGCGGUGGAGG 24

7136 26016

CFTR- IntronlO- - UCCUAGCACUUUUGGAGG 18

7137 26017

CFTR- IntronlO- - AUCCUAGCACUUUUGGAGG 19

7138 26018

CFTR- IntronlO- - AAUCCUAGCACUUUUGGAGG 20

7139 26019

CFTR- IntronlO- - UAAUCCUAGCACUUUUGGAGG 21

7140 26020

CFTR- IntronlO- - GUAAUCCUAGCACUUUUGGAGG 22

7141 26021

CFTR- IntronlO- - UGUAAUCCUAGCACUUUUGGAGG 23

7142 26022

CFTR- IntronlO- - UUGUAAUCCUAGCACUUUUGGAGG 24

7143 26023

CFTR- IntronlO- - AGAAAGAAGGAAAUGAGG 18

7144 26024

CFTR- IntronlO- - AAGAAAGAAGGAAAUGAGG 19

7145 26025

CFTR- IntronlO- - GAAGAAAGAAGGAAAUGAGG 20

7146 26026

CFTR- IntronlO- - G G A AG A A AG A AG G AAA U G AG G 21

7147 26027

CFTR- IntronlO- - AG G AAG AAAG AAG G AAAU G AG G 22

7148 26028

CFTR- IntronlO- - AAGGAAGAAAGAAGGAAAUGAGG 23

7149 26029

1098

5535.1 CFTR- IntronlO- - GAAGGAAGAAAGAAGGAAAUGAGG 24

7150 26030

CFTR- IntronlO- - GGUGAUUAGUCCAUGAGG 18

7151 26031

CFTR- IntronlO- - AGGUGAUUAGUCCAUGAGG 19

7152 26032

CFTR- IntronlO- - GAGGUGAUUAGUCCAUGAGG 20

7153 26033

CFTR- IntronlO- - GGAGGUGAUUAGUCCAUGAGG 21

7154 26034

CFTR- IntronlO- - GGGAGGUGAUUAGUCCAUGAGG 22

7155 26035

CFTR- IntronlO- - UGGGAGGUGAUUAGUCCAUGAGG 23

7156 26036

CFTR- IntronlO- - UUGGGAGGUGAUUAGUCCAUGAGG 24

7157 26037

CFTR- IntronlO- - CUACUCGGGAGGCUGAGG 18

7158 26038

CFTR- IntronlO- - GCUACUCGGGAGGCUGAGG 19

7159 26039

CFTR- IntronlO- - AGCUACUCGGGAGGCUGAGG 20

7160 26040

CFTR- IntronlO- - CAGCUACUCGGGAGGCUGAGG 21

7161 26041

CFTR- IntronlO- - CCAGCUACUCGGGAGGCUGAGG 22

7162 26042

CFTR- IntronlO- - CCCAGCUACUCGGGAGGCUGAGG 23

7163 26043

1099

5535.1 CFTR- IntronlO- - UCCCAGCUACUCGGGAGGCUGAGG 24

7164 26044

CFTR- IntronlO- - CUACUUGGGAGGCUGAGG 18

7165 26045

CFTR- IntronlO- - GCUACUUGGGAGGCUGAGG 19

7166 26046

CFTR- IntronlO- - AGCUACUUGGGAGGCUGAGG 20

1288 20173

CFTR- IntronlO- - AAAAAAUUAUACUAUAGG 18

7167 26047

CFTR- IntronlO- - UAAAAAAUUAUACUAUAGG 19

7168 26048

CFTR- IntronlO- - UU AAAAAAUUAUACUAUAGG 20

1289 20174

CFTR- IntronlO- - AUUAAAAAAUUAUACUAUAGG 21

7169 26049

CFTR- IntronlO- - UAUUAAAAAAUUAUACUAUAGG 22

7170 26050

CFTR- IntronlO- - CUAUUAAAAAAUUAUACUAUAGG 23

7171 26051

CFTR- IntronlO- - ACUAUUAAAAAAUUAUACUAUAGG 24

7172 26052

CFTR- IntronlO- - AGGAAGAAAGGAAGUAGG 18

7173 26053

CFTR- IntronlO- - GAGGAAGAAAGGAAGUAGG 19

7174 26054

CFTR- IntronlO- - UG AGGAAGAAAGGAAGUAGG 20

1290 20175

1100

5535.1 CFTR- IntronlO- - AUGAGGAAGAAAGGAAGUAGG 21

7175 26055

CFTR- IntronlO- - AAUGAGGAAG A A AG G A AG U AG G 22

7176 26056

CFTR- IntronlO- - AAAUGAGGAAGAAAGGAAGUAGG 23

7177 26057

CFTR- IntronlO- - GAAAUGAGGAAGAAAGGAAGUAGG 24

7178 26058

CFTR- IntronlO- - CAGAGAAGUAAUCGGCGG 18

7179 26059

CFTR- IntronlO- - UCAGAGAAGUAAUCGGCGG 19

7180 26060

CFTR-

- GUCAGAGAAGUAAUCGGCGG 20

lntronlO-105 18991

CFTR- IntronlO- - UGUCAGAGAAGUAAUCGGCGG 21

7181 26061

CFTR- IntronlO- - CUGUCAGAGAAGUAAUCGGCGG 22

7182 26062

CFTR- IntronlO- - ACUGUCAGAGAAGUAAUCGGCGG 23

7183 26063

CFTR- IntronlO- - UACUGUCAGAGAAGUAAUCGGCGG 24

7184 26064

CFTR- IntronlO- - UCUGUAGGGAGACAAGGG 18

7185 26065

CFTR- IntronlO- - UUCUGUAGGGAGACAAGGG 19

7186 26066

CFTR-

- AUUCUGUAGGGAGACAAGGG 20

lntronlO-473 19359

CFTR- IntronlO- - UAUUCUGUAGGGAGACAAGGG 21

7187 26067

1101

5535.1 CFTR- IntronlO- - CUAUUCUGUAGGGAGACAAGGG 22

7188 26068

CFTR- IntronlO- - GCUAUUCUGUAGGGAGACAAGGG 23

7189 26069

CFTR- IntronlO- - GGCUAUUCUGUAGGGAGACAAGGG 24

7190 26070

CFTR- IntronlO- - GGUGAUGGUAUUGCAGGG 18

7191 26071

CFTR- IntronlO- - AGGUGAUGGUAUUGCAGGG 19

7192 26072

CFTR- IntronlO- - AAGGUGAUGGUAUUGCAGGG 20

1292 20177

CFTR- IntronlO- - CAAGGUGAUGGUAUUGCAGGG 21

7193 26073

CFTR- IntronlO- - CCAAGGUGAUGGUAUUGCAGGG 22

7194 26074

CFTR- IntronlO- - CCCAAGGUGAUGGUAUUGCAGGG 23

7195 26075

CFTR- IntronlO- - UCCCAAGGUGAUGGUAUUGCAGGG 24

7196 26076

CFTR- IntronlO- - C AG G AG CCA A A A A U U G G G 18

7197 26077

CFTR- IntronlO- - UCAGGAGCCAAAAAUUGGG 19

7198 26078

CFTR-

- UUCAGGAGCCAAAAAUUGGG 20

lntronlO-476 19362

CFTR- IntronlO- - UU UCAGGAGCCAAAAAUUGGG 21

7199 26079

CFTR-

- CUU UCAGGAGCCAAAAAUUGGG 22

IntronlO- 26080

1102

5535.1 7200

CFTR- IntronlO- - GCUUUCAGGAGCCAAAAAUUGGG 23

7201 26081

CFTR- IntronlO- - UGCUUUCAGGAGCCAAAAAUUGGG 24

7202 26082

CFTR- IntronlO- - UUACUAGAAAGAUAAUGG 18

7203 26083

CFTR- IntronlO- - UUUACUAGAAAGAUAAUGG 19

7204 26084

CFTR- IntronlO- - GUUUACUAGAAAGAUAAUGG 20

7205 26085

CFTR- IntronlO- - CGUUUACUAGAAAGAUAAUGG 21

7206 26086

CFTR- IntronlO- - CCGUUUACUAGAAAGAUAAUGG 22

7207 26087

CFTR- IntronlO- - GCCGUUUACUAGAAAGAUAAUGG 23

7208 26088

CFTR- IntronlO- - UGCCGUUUACUAGAAAGAUAAUGG 24

7209 26089

CFTR- IntronlO- - UAAGGCUUAUUUCUCUGG 18

7210 26090

CFTR- IntronlO- - CUAAGGCUUAUUUCUCUGG 19

7211 26091

CFTR- IntronlO- - ACUAAGGCUUAUUUCUCUGG 20

7212 26092

CFTR- IntronlO- - GACUAAGGCUUAUUUCUCUGG 21

7213 26093

CFTR-

- AGACUAAGGCUUAUUUCUCUGG 22

IntronlO- 26094

1103

5535.1 7214

CFTR- IntronlO- - AAGACUAAGGCUUAUUUCUCUGG 23

7215 26095

CFTR- IntronlO- - AAAGACUAAGGCUUAUUUCUCUGG 24

7216 26096

CFTR- IntronlO- - UAGAGGUUAAGGAGGUGG 18

7217 26097

CFTR- IntronlO- - UUAGAGGUUAAGGAGGUGG 19

7218 26098

CFTR- IntronlO- - AUUAGAGGUUAAGGAGGUGG 20

7219 26099

CFTR- IntronlO- - UAUUAGAGGUUAAGGAGGUGG 21

7220 26100

CFTR- IntronlO- - GUAUUAGAGGUUAAGGAGGUGG 22

7221 26101

CFTR- IntronlO- - AGUAUUAGAGGUUAAGGAGGUGG 23

7222 26102

CFTR- IntronlO- - AAGUAUUAGAGGUUAAGGAGGUGG 24

7223 26103

CFTR- IntronlO- - GAGCCAAAAAUUGGGUGG 18

7224 26104

CFTR- IntronlO- - GGAGCCAAAAAUUGGGUGG 19

7225 26105

CFTR-

- AGGAGCCAAAAAUUGGGUGG 20

lntronlO-478 19364

CFTR- IntronlO- - CAGGAGCCAAAAAUUGGGUGG 21

7226 26106

CFTR- IntronlO- - UCAGGAGCCAAAAAUUGGGUGG 22

7227 26107

1104

5535.1 CFTR- IntronlO- - UUCAGGAGCCAAAAAUUGGGUGG 23

7228 26108

CFTR- IntronlO- - UUUCAGGAGCCAAAAAUUGGGUGG 24

7229 26109

CFTR- IntronlO- - UCAGGAGCCAAAAAUUGG 18

7230 26110

CFTR- IntronlO- - UUCAGGAGC C A A A A A U U G G 19

7231 26111

CFTR- IntronlO- - UUUCAGGAGC C A A A A A U U G G 20

7232 26112

CFTR- IntronlO- - CUUUCAGGAGCCAAAAAUUGG 21

7233 26113

CFTR- IntronlO- - GCUUUCAGGAGCCAAAAAUUGG 22

7234 26114

CFTR- IntronlO- - UGCUUUCAGGAGCCAAAAAUUGG 23

7235 26115

CFTR- IntronlO- - CUGCUUUCAGGAGCCAAAAAUUGG 24

7236 26116

CFTR- IntronlO- - GGGAGAAACAGGUUUUGG 18

7237 26117

CFTR- IntronlO- - UGGGAGAAACAGGUUUUGG 19

7238 26118

CFTR- IntronlO- - AUGGGAGAAACAGGUUUUGG 20

7239 26119

CFTR- IntronlO- - AAUGGGAGAAACAGGUUUUGG 21

7240 26120

CFTR- IntronlO- - UAAUGGGAGAAACAGGUUUUGG 22

7241 26121

1105

5535.1 CFTR- IntronlO- - AUAAUGGGAGAAACAGGUUUUGG 23

7242 26122

CFTR- IntronlO- - GAUAAUGGGAGAAACAGGUUUUGG 24

7243 26123

CFTR- IntronlO- - GGAAGAAAGAAGGAAAUG 18

7244 26124

CFTR- IntronlO- - AGGAAGAAAGAAGGAAAUG 19

7245 26125

CFTR- IntronlO- - A AG G A AG A A AG A AG G AAA U G 20

1311 20196

CFTR- IntronlO- - GAAGGAAGAAAGAAGGAAAUG 21

7246 26126

CFTR- IntronlO- - G G A AG G A AG A A AG A AG G AAA U G 22

7247 26127

CFTR- IntronlO- - AGGAAGGAAGAAAGAAGGAAAUG 23

7248 26128

CFTR- IntronlO- - GAGGAAGGAAGAAAGAAGGAAAUG 24

7249 26129

CFTR- IntronlO- - UUAUCAAUAUCUAAGAUG 18

7250 26130

CFTR- IntronlO- - UUUAUCAAUAUCUAAGAUG 19

7251 26131

CFTR-

- AUUUAUCAAUAUCUAAGAUG 20

lntronlO-480 19366

CFTR- IntronlO- - UAUUUAUCAAUAUCUAAGAUG 21

7252 26132

CFTR- IntronlO- - UUAUUUAUCAAUAUCUAAGAUG 22

7253 26133

CFTR-

- AUUAUUUAUCAAUAUCUAAGAUG 23

IntronlO- 26134

1106

5535.1 7254

CFTR- IntronlO- - AAUUAUUUAUCAAUAUCUAAGAUG 24

7255 26135

CFTR- IntronlO- - UCCCCUGCCAUUCAUAUG 18

7256 26136

CFTR- IntronlO- - CUCCCCUGCCAUUCAUAUG 19

7257 26137

CFTR- IntronlO- - UCUCCCCUGCCAUUCAUAUG 20

7258 26138

CFTR- IntronlO- - CUCUCCCCUGCCAUUCAUAUG 21

7259 26139

CFTR- IntronlO- - UCUCUCCCCUGCCAUUCAUAUG 22

7260 26140

CFTR- IntronlO- - GUCUCUCCCCUGCCAUUCAUAUG 23

7261 26141

CFTR- IntronlO- - UGUCUCUCCCCUGCCAUUCAUAUG 24

7262 26142

CFTR- IntronlO- - UGUUUUUAGGCUAUUCUG 18

7263 26143

CFTR- IntronlO- - AUGUUUUUAGGCUAUUCUG 19

7264 26144

CFTR- IntronlO- - AAUGUUUUUAGGCUAUUCUG 20

7265 26145

CFTR- IntronlO- - UAAUGUUUUUAGGCUAUUCUG 21

7266 26146

CFTR- IntronlO- - CUAAUGUUUUUAGGCUAUUCUG 22

7267 26147

CFTR-

- GCUAAUGUUUUUAGGCUAUUCUG 23

IntronlO- 26148

1107

5535.1 7268

CFTR- IntronlO- - GGCUAAUGUUUUUAGGCUAUUCUG 24

7269 26149

CFTR- IntronlO- - CCUCGGCCUCCCAAAGUG 18

7270 26150

CFTR- IntronlO- - GCCUCGGCCUCCCAAAGUG 19

7271 26151

CFTR- IntronlO- - CGCCUCGGCCUCCCAAAGUG 20

7272 26152

CFTR- IntronlO- - CCGCCUCGGCCUCCCAAAGUG 21

7273 26153

CFTR- IntronlO- - CCCGCCUCGGCCUCCCAAAGUG 22

7274 26154

CFTR- IntronlO- - GCCCGCCUCGGCCUCCCAAAGUG 23

7275 26155

CFTR- IntronlO- - CGCCCGCCUCGGCCUCCCAAAGUG 24

7276 26156

CFTR- IntronlO- - UGCCUCGGCCUCCCAAAGUG 20

7277 26157

CFTR- IntronlO- - CUGCCUCGGCCUCCCAAAGUG 21

7278 26158

CFTR- IntronlO- - CCUGCCUCGGCCUCCCAAAGUG 22

7279 26159

CFTR- IntronlO- - GCCUGCCUCGGCCUCCCAAAGUG 23

7280 26160

CFTR- IntronlO- - UGCCUGCCUCGGCCUCCCAAAGUG 24

7281 26161

CFTR-

- CCAGGCUGGAGUGCAGUG 18

IntronlO- 26162

1108

5535.1 7282

CFTR- IntronlO- - CCCAGGCUGGAGUGCAGUG 19

7283 26163

CFTR- IntronlO- - GCCCAGGCUGGAGUGCAGUG 20

7284 26164

CFTR- IntronlO- - CGCCCAGGCUGGAGUGCAGUG 21

7285 26165

CFTR- IntronlO- - UCGCCCAGGCUGGAGUGCAGUG 22

7286 26166

CFTR- IntronlO- - GUCGCCCAGGCUGGAGUGCAGUG 23

7287 26167

CFTR- IntronlO- - UGUCGCCCAGGCUGGAGUGCAGUG 24

7288 26168

CFTR- IntronlO- - UAAGAAGAGAAAGGGGUG 18

7289 26169

CFTR- IntronlO- - A U A AG A AG AG A A AG G G G U G 19

7290 26170

CFTR- IntronlO- - GAUAAGAAGAGAAAGGGGUG 20

7291 26171

CFTR- IntronlO- - UGAUAAGAAGAGAAAGGGGUG 21

7292 26172

CFTR- IntronlO- - UUGAUAAGAAGAGAAAGGGGUG 22

7293 26173

CFTR- IntronlO- - GUUGAUAAGAAGAGAAAGGGGUG 23

7294 26174

CFTR- IntronlO- - GGUUGAUAAGAAGAGAAAGGGGUG 24

7295 26175

CFTR-

- AGGUUAAGGAGGUGGGUG 18

IntronlO- 26176

1109

5535.1 7296

CFTR- IntronlO- - GAGGUUAAGGAGGUGGGUG 19

7297 26177

CFTR- IntronlO- - AGAGGUUAAGGAGGUGGGUG 20

7298 26178

CFTR- IntronlO- - UAGAGGUUAAGGAGGUGGGUG 21

7299 26179

CFTR- IntronlO- - UUAGAGGUUAAGGAGGUGGGUG 22

7300 26180

CFTR- IntronlO- - AUUAGAGGUUAAGGAGGUGGGUG 23

7301 26181

CFTR- IntronlO- - UAUUAGAGGUUAAGGAGGUGGGUG 24

7302 26182

CFTR- IntronlO- - GGAGCCAAAAAUUGGGUG 18

7303 26183

CFTR- IntronlO- - AGGAGCCAAAAAUUGGGUG 19

7304 26184

CFTR-

- C AG G AG CCA A A A A U U G G G U G 20

lntronlO-489 19375

CFTR- IntronlO- - UCAGGAGCCAAAAAUUGGGUG 21

7305 26185

CFTR- IntronlO- - UUCAGGAGCCAAAAAUUGGGUG 22

7306 26186

CFTR- IntronlO- - UUUCAGGAGCCAAAAAUUGGGUG 23

7307 26187

CFTR- IntronlO- - CUUUCAGGAGCCAAAAAUUGGGUG 24

7308 26188

CFTR- IntronlO- - UGGCAUCUCACCAGUGUG 18

7309 26189

1110

5535.1 CFTR- IntronlO- - AUGGCAUCUCACCAGUGUG 19

7310 26190

CFTR-

- UAUGGCAUCUCACCAGUGUG 20

lntronlO-491 19377

CFTR- IntronlO- - UUAUGGCAUCUCACCAGUGUG 21

7311 26191

CFTR- IntronlO- - CUUAUGGCAUCUCACCAGUGUG 22

7312 26192

CFTR- IntronlO- - GCUUAUGGCAUCUCACCAGUGUG 23

7313 26193

CFTR- IntronlO- - GGCUUAUGGCAUCUCACCAGUGUG 24

7314 26194

CFTR- IntronlO- - UUAUAAAAAAUAAUUGUG 18

7315 26195

CFTR- IntronlO- - UUUAUAAAAAAUAAUUGUG 19

7316 26196

CFTR- IntronlO- - U U U UAU AAAAAAU AAU UG UG 20

7317 26197

CFTR- IntronlO- - U U U U UAU AAAAAAU AAU UG UG 21

7318 26198

CFTR- IntronlO- - AUUUUUAUAAAAAAUAAUUGUG 22

7319 26199

CFTR- IntronlO- - GAUUUUUAUAAAAAAUAAUUGUG 23

7320 26200

CFTR- IntronlO- - AG AU U U U UAU AAAAAAU AAU UG UG 24

7321 26201

CFTR- IntronlO- - G CAG U U U U AU U AAAAU UG 18

7322 26202

CFTR-

- GGCAGUUUUAUUAAAAUUG 19

IntronlO- 26203

1111

5535.1 7323

CFTR- IntronlO- - AGG CAG U U U U AU U AAAAU UG 20

7324 26204

CFTR- IntronlO- - CAGGCAGUUUUAUUAAAAUUG 21

7325 26205

CFTR- IntronlO- - UCAGGCAGUUUUAUUAAAAUUG 22

7326 26206

CFTR- IntronlO- - U U CAGG CAG U U U U AU U AAAAU UG 23

7327 26207

CFTR- IntronlO- - U U U CAGG CAG U U U U AU U AAAAU UG 24

7328 26208

CFTR- IntronlO- - GCUCUCUUUUAACUAUUG 18

7329 26209

CFTR- IntronlO- - UGCUCUCUUUUAACUAUUG 19

7330 26210

CFTR-

- UUGCUCUCUUUUAACUAUUG 20

lntronlO-495 19381

CFTR- IntronlO- - CUUGCUCUCUUUUAACUAUUG 21

7331 26211

CFTR- IntronlO- - ACUUGCUCUCUUUUAACUAUUG 22

7332 26212

CFTR- IntronlO- - AACUUGCUCUCUUUUAACUAUUG 23

7333 26213

CFTR- IntronlO- - AAACUUGCUCUCUUUUAACUAUUG 24

7334 26214

CFTR- IntronlO- - CAU U UG AACAAAG ACU U G 18

7335 26215

CFTR- IntronlO- - ACAUUUGAACAAAGACUUG 19

7336 26216

1112

5535.1 CFTR- IntronlO- - AACAU UUGAACAAAGACUUG 20

7337 26217

CFTR- IntronlO- - U AACAU UUG AACAAAG ACU UG 21

7338 26218

CFTR- IntronlO- - G U AACAU U UG AACAAAG ACU UG 22

7339 26219

CFTR- IntronlO- - GG U AACAU U UG AACAAAG ACU UG 23

7340 26220

CFTR- IntronlO- - AGGUAACAUUUGAACAAAGACUUG 24

7341 26221

CFTR- IntronlO- - UUUAGCUGUGGUACUUUG 18

7342 26222

CFTR- IntronlO- - UUUUAGCUGUGGUACUUUG 19

7343 26223

CFTR- IntronlO- - AUUUUAGCUGUGGUACUUUG 20

7344 26224

CFTR- IntronlO- - CAUUUUAGCUGUGGUACUUUG 21

7345 26225

CFTR- IntronlO- - UCAUUUUAGCUGUGGUACUUUG 22

7346 26226

CFTR- IntronlO- - GUCAUUUUAGCUGUGGUACUUUG 23

7347 26227

CFTR- IntronlO- - UGUCAUUUUAGCUGUGGUACUUUG 24

7348 26228

CFTR- IntronlO- - GAUUCAGGACAUGCUUUG 18

7349 26229

CFTR- IntronlO- - AGAUUCAGGACAUGCUUUG 19

7350 26230

1113

5535.1 CFTR- IntronlO- - CAGAUUCAGGACAUGCUUUG 20

7351 26231

CFTR- IntronlO- - UCAGAUUCAGGACAUGCUUUG 21

7352 26232

CFTR- IntronlO- - AUCAGAUUCAGGACAUGCUUUG 22

7353 26233

CFTR- IntronlO- - GAUCAGAUUCAGGACAUGCUUUG 23

7354 26234

CFTR- IntronlO- - UGAUCAGAUUCAGGACAUGCUUUG 24

7355 26235

CFTR- IntronlO- - CUAUACCUGUCUGGUUUG 18

7356 26236

CFTR- IntronlO- - ACUAUACCUGUCUGGUUUG 19

7357 26237

CFTR- IntronlO- - GACUAUACCUGUCUGGUUUG 20

7358 26238

CFTR- IntronlO- - UGACUAUACCUGUCUGGUUUG 21

7359 26239

CFTR- IntronlO- - CUGACUAUACCUGUCUGGUUUG 22

7360 26240

CFTR- IntronlO- - ACUGACUAUACCUGUCUGGUUUG 23

7361 26241

CFTR- IntronlO- - GACUGACUAUACCUGUCUGGUUUG 24

7362 26242

CFTR- IntronlO- - CUUACCCAAAUAUGUUUG 18

7363 26243

CFTR- IntronlO- - ACUUACCCAAAUAUGUUUG 19

7364 26244

1114

5535.1 CFTR- IntronlO- - AACUUACCCAAAUAUGUUUG 20

7365 26245

CFTR- IntronlO- - UAACUUACCCAAAUAUGUUUG 21

7366 26246

CFTR- IntronlO- - AUAACUUACCCAAAUAUGUUUG 22

7367 26247

CFTR- IntronlO- - UAUAACUUACCCAAAUAUGUUUG 23

7368 26248

CFTR- IntronlO- - CUAUAACUUACCCAAAUAUGUUUG 24

7369 26249

CFTR- IntronlO- - U U ACCCAAU AAAAAAAAU 18

7370 26250

CFTR- IntronlO- - G U U ACCCAAU AAAAAAAAU 19

7371 26251

CFTR- IntronlO- - UG U U ACCCAAU AAAAAAAAU 20

7372 26252

CFTR- IntronlO- - U UG U U ACCCAAU AAAAAAAAU 21

7373 26253

CFTR- IntronlO- - AUUGUUACCCAAUAAAAAAAAU 22

7374 26254

CFTR- IntronlO- - U AU UG U U ACCCAAU AAAAAAAAU 23

7375 26255

CFTR- IntronlO- - U U AU UG U U ACCCAAU AAAAAAAAU 24

7376 26256

CFTR- IntronlO- - UUUUGCAAAAUACAAAAU 18

7377 26257

CFTR- IntronlO- - U U U U U G C A A A A U AC A A A A U 19

7378 26258

1115

5535.1 CFTR- IntronlO- - CU U U U UG CAAAAU ACAAAAU 20

7379 26259

CFTR- IntronlO- - ACU U U U UG CAAAAU ACAAAAU 21

7380 26260

CFTR- IntronlO- - CACUUUUUGCAAAAUACAAAAU 22

7381 26261

CFTR- IntronlO- - G CACU U U U U GCAAAAU ACAAAAU 23

7382 26262

CFTR- IntronlO- - UGCACUUUUUGCAAAAUACAAAAU 24

7383 26263

CFTR- IntronlO- - AACAAAAGAAAAGAAAAU 18

7384 26264

CFTR- IntronlO- - UAACAAAAGAAAAGAAAAU 19

7385 26265

CFTR- IntronlO- - GU AACAAAAGAAAAGAAAAU 20

7386 26266

CFTR- IntronlO- - UG UAACAAAAGAAAAGAAAAU 21

7387 26267

CFTR- IntronlO- - U UG UAACAAAAGAAAAGAAAAU 22

7388 26268

CFTR- IntronlO- - GUUGUAACAAAAGAAAAGAAAAU 23

7389 26269

CFTR- IntronlO- - UGUUGUAACAAAAGAAAAGAAAAU 24

7390 26270

CFTR- IntronlO- - GACAUGAAAGAAUCAAAU 18

7391 26271

CFTR- IntronlO- - AGACAUGAAAGAAUCAAAU 19

7392 26272

1116

5535.1 CFTR- IntronlO- - AAGACAUGAAAGAAUCAAAU 20

7393 26273

CFTR- IntronlO- - AAAGACAUGAAAGAAUCAAAU 21

7394 26274

CFTR- IntronlO- - U A A AG AC A U G A A AG A A U C A A A U 22

7395 26275

CFTR- IntronlO- - UUAAAGACAUGAAAGAAUCAAAU 23

7396 26276

CFTR- IntronlO- - U U U AAAG ACAUG AAAG AAU CAAAU 24

7397 26277

CFTR- IntronlO- - GUGGUACUUUGUAGAAAU 18

7398 26278

CFTR- IntronlO- - UGUGGUACUUUGUAGAAAU 19

7399 26279

CFTR- IntronlO- - CUGUGGUACUUUGUAGAAAU 20

7400 26280

CFTR- IntronlO- - GCUGUGGUACUUUGUAGAAAU 21

7401 26281

CFTR- IntronlO- - AGCUGUGGUACUUUGUAGAAAU 22

7402 26282

CFTR- IntronlO- - UAGCUGUGGUACUUUGUAGAAAU 23

7403 26283

CFTR- IntronlO- - UUAGCUGUGGUACUUUGUAGAAAU 24

7404 26284

CFTR- IntronlO- - AGGAAGAAAGAAGGAAAU 18

7405 26285

CFTR- IntronlO- - AAGGAAGAAAGAAGGAAAU 19

7406 26286

1117

5535.1 CFTR- IntronlO- - GAAGGAAGAAAGAAGGAAAU 20

7407 26287

CFTR- IntronlO- - GGAAGGAAGAAAGAAGGAAAU 21

7408 26288

CFTR- IntronlO- - AGGAAGGAAGAAAGAAGGAAAU 22

7409 26289

CFTR- IntronlO- - GAGGAAGGAAGAAAGAAGGAAAU 23

7410 26290

CFTR- IntronlO- - AGAGGAAGGAAGAAAGAAGGAAAU 24

7411 26291

CFTR- IntronlO- - ACU UGACCAG AAUGAAAU 18

7412 26292

CFTR- IntronlO- - AACUUGACCAGAAUGAAAU 19

7413 26293

CFTR- IntronlO- - AAACU UGACCAG AAUGAAAU 20

7414 26294

CFTR- IntronlO- - CAAACUUGACCAGAAUGAAAU 21

7415 26295

CFTR- IntronlO- - UCAAACUUGACCAGAAUGAAAU 22

7416 26296

CFTR- IntronlO- - GUCAAACUUGACCAGAAUGAAAU 23

7417 26297

CFTR- IntronlO- - GGUCAAACUUGACCAGAAUGAAAU 24

7418 26298

CFTR- IntronlO- - ACCGGUGUCUUCUGAAAU 18

7419 26299

CFTR- IntronlO- - AACCGGUGUCUUCUGAAAU 19

7420 26300

1118

5535.1 CFTR- IntronlO- - UAACCGGUGUCUUCUGAAAU 20

7421 26301

CFTR- IntronlO- - UUAACCGGUGUCUUCUGAAAU 21

7422 26302

CFTR- IntronlO- - AUUAACCGGUGUCUUCUGAAAU 22

7423 26303

CFTR- IntronlO- - AAUUAACCGGUGUCUUCUGAAAU 23

7424 26304

CFTR- IntronlO- - UAAUUAACCGGUGUCUUCUGAAAU 24

7425 26305

CFTR- IntronlO- - UUGGGGUUUUUUGACAAU 18

7426 26306

CFTR- IntronlO- - UUUGGGGUUUUUUGACAAU 19

7427 26307

CFTR- IntronlO- - UUUUGGGGUUUUUUGACAAU 20

7428 26308

CFTR- IntronlO- - UUUUUGGGGUUUUUUGACAAU 21

7429 26309

CFTR- IntronlO- - AUUUUUGGGGUUUUUUGACAAU 22

7430 26310

CFTR- IntronlO- - AAUUUUUGGGGUUUUUUGACAAU 23

7431 26311

CFTR- IntronlO- - AAAUUUUUGGGGUUUUUUGACAAU 24

7432 26312

CFTR- IntronlO- - AAUGAAAUUAGAAAGAAU 18

7433 26313

CFTR- IntronlO- - GAAUGAAAUUAGAAAGAAU 19

7434 26314

1119

5535.1 CFTR- IntronlO- - AGAAUGAAAUUAGAAAGAAU 20

7435 26315

CFTR- IntronlO- - C AG A A U G AAA U U AG A A AG A A U 21

7436 26316

CFTR- IntronlO- - CCAGAAUGAAAUUAGAAAGAAU 22

7437 26317

CFTR- IntronlO- - ACCAGAAUGAAAUUAGAAAGAAU 23

7438 26318

CFTR- IntronlO- - GACCAGAAUGAAAUUAGAAAGAAU 24

7439 26319

CFTR- IntronlO- - UAUUUUGAAGAAUUGAAU 18

7440 26320

CFTR- IntronlO- - AUAUUUUGAAGAAUUGAAU 19

7441 26321

CFTR- IntronlO- - CAU AU U UUGAAGAAU U GAAU 20

7442 26322

CFTR- IntronlO- - CCAUAUUUUGAAGAAUUGAAU 21

7443 26323

CFTR- IntronlO- - ACCAUAUUUUGAAGAAUUGAAU 22

7444 26324

CFTR- IntronlO- - AACCAUAUUUUGAAGAAUUGAAU 23

7445 26325

CFTR- IntronlO- - GAACCAUAUUUUGAAGAAUUGAAU 24

7446 26326

CFTR- IntronlO- - UGGUACUACUGUAAUAAU 18

7447 26327

CFTR- IntronlO- - AUGGUACUACUGUAAUAAU 19

7448 26328

1120

5535.1 CFTR- IntronlO- - UAUGGUACUACUGUAAUAAU 20

7449 26329

CFTR- IntronlO- - AUAUGGUACUACUGUAAUAAU 21

7450 26330

CFTR- IntronlO- - CAUAUGGUACUACUGUAAUAAU 22

7451 26331

CFTR- IntronlO- - ACAUAUGGUACUACUGUAAUAAU 23

7452 26332

CFTR- IntronlO- - UACAUAUGGUACUACUGUAAUAAU 24

7453 26333

CFTR- IntronlO- - GUUUACUAGAAAGAUAAU 18

7454 26334

CFTR- IntronlO- - CGUUUACUAGAAAGAUAAU 19

7455 26335

CFTR-

- CCGUUUACUAGAAAGAUAAU 20

lntronlO-501 19387

CFTR- IntronlO- - GCCGUUUACUAGAAAGAUAAU 21

7456 26336

CFTR- IntronlO- - UGCCGUUUACUAGAAAGAUAAU 22

7457 26337

CFTR- IntronlO- - G UG CCG U U U ACU AG AAAG AU AAU 23

7458 26338

CFTR- IntronlO- - UGUGCCGUUUACUAGAAAGAUAAU 24

7459 26339

CFTR- IntronlO- - UGACUCUAGUUCACUAAU 18

7460 26340

CFTR- IntronlO- - GUGACUCUAGUUCACUAAU 19

7461 26341

CFTR-

- UGUGACUCUAGUUCACUAAU 20

IntronlO- 26342

1121

5535.1 7462

CFTR- IntronlO- - AUGUGACUCUAGUUCACUAAU 21

7463 26343

CFTR- IntronlO- - UAUGUGACUCUAGUUCACUAAU 22

7464 26344

CFTR- IntronlO- - CUAUGUGACUCUAGUUCACUAAU 23

7465 26345

CFTR- IntronlO- - UCUAUGUGACUCUAGUUCACUAAU 24

7466 26346

CFTR- IntronlO- - AACAUUGAAAGGUAACAU 18

7467 26347

CFTR- IntronlO- - AAACAU UG AAAGG U AACAU 19

7468 26348

CFTR- IntronlO- - U AAACAU UG AAAGG U AACAU 20

7469 26349

CFTR- IntronlO- - UU AAACAU UG AAAGG U AACAU 21

7470 26350

CFTR- IntronlO- - U U U AAACAU UG AAAGG U AACAU 22

7471 26351

CFTR- IntronlO- - CU U U AAACAU UG AAAGG U AACAU 23

7472 26352

CFTR- IntronlO- - CCUUUAAACAUUGAAAGGUAACAU 24

7473 26353

CFTR- IntronlO- - UUUUUUCAGUUAAUACAU 18

7474 26354

CFTR- IntronlO- - UUUUUUUCAGUUAAUACAU 19

7475 26355

CFTR-

- UUUUUUUUCAGUUAAUACAU 20

IntronlO- 20217

1122

5535.1 1332

CFTR- IntronlO- - AUUUUUUUUCAGUUAAUACAU 21

7476 26356

CFTR- IntronlO- - AAUUUUUUUUCAGUUAAUACAU 22

7477 26357

CFTR- IntronlO- - GAAUUUUUUUUCAGUUAAUACAU 23

7478 26358

CFTR- IntronlO- - UGAAUUUUUUUUCAGUUAAUACAU 24

7479 26359

CFTR- IntronlO- - GCAUAUUUGGAGAUACAU 18

7480 26360

CFTR- IntronlO- - GGCAUAUUUGGAGAUACAU 19

7481 26361

CFTR- IntronlO- - UGGCAUAUUUGGAGAUACAU 20

7482 26362

CFTR- IntronlO- - CUGGCAUAUUUGGAGAUACAU 21

7483 26363

CFTR- IntronlO- - CCUGGCAUAUUUGGAGAUACAU 22

7484 26364

CFTR- IntronlO- - ACCUGGCAUAUUUGGAGAUACAU 23

7485 26365

CFTR- IntronlO- - AACCUGGCAUAUUUGGAGAUACAU 24

7486 26366

CFTR- IntronlO- - CCAGUUGUUUUCCUACAU 18

7487 26367

CFTR- IntronlO- - UCCAGUUGUUUUCCUACAU 19

7488 26368

CFTR-

- CUCCAGUUGUUUUCCUACAU 20

IntronlO- 26369

1123

5535.1 7489

CFTR- IntronlO- - UCUCCAGUUGUUUUCCUACAU 21

7490 26370

CFTR- IntronlO- - CUCUCCAGUUGUUUUCCUACAU 22

7491 26371

CFTR- IntronlO- - UCUCUCCAGUUGUUUUCCUACAU 23

7492 26372

CFTR- IntronlO- - CUCUCUCCAGUUGUUUUCCUACAU 24

7493 26373

CFTR- IntronlO- - CUCACCCCUUUCUGCCAU 18

7494 26374

CFTR- IntronlO- - CCUCACCCCUUUCUGCCAU 19

7495 26375

CFTR- IntronlO- - CCCUCACCCCUUUCUGCCAU 20

7496 26376

CFTR- IntronlO- - ACCCUCACCCCUUUCUGCCAU 21

7497 26377

CFTR- IntronlO- - GACCCUCACCCCUUUCUGCCAU 22

7498 26378

CFTR- IntronlO- - AGACCCUCACCCCUUUCUGCCAU 23

7499 26379

CFTR- IntronlO- - GAGACCCUCACCCCUUUCUGCCAU 24

7500 26380

CFTR- IntronlO- - UAAGUUGAACAAUGGCAU 18

7501 26381

CFTR- IntronlO- - AUAAGUUGAACAAUGGCAU 19

7502 26382

CFTR-

- GAUAAGUUGAACAAUGGCAU 20

IntronlO- 26383

1124

5535.1 7503

CFTR- IntronlO- - GGAUAAGUUGAACAAUGGCAU 21

7504 26384

CFTR- IntronlO- - UGGAUAAGUUGAACAAUGGCAU 22

7505 26385

CFTR- IntronlO- - AUGGAUAAGUUGAACAAUGGCAU 23

7506 26386

CFTR- IntronlO- - AAUGGAUAAGUUGAACAAUGGCAU 24

7507 26387

CFTR- IntronlO- - AAAAUAUCACCAACUCAU 18

7508 26388

CFTR- IntronlO- - AAAAAUAUCACCAACUCAU 19

7509 26389

CFTR- IntronlO- - GAAAAAUAUCACCAACUCAU 20

7510 26390

CFTR- IntronlO- - UGAAAAAUAUCACCAACUCAU 21

7511 26391

CFTR- IntronlO- - AUGAAAAAUAUCACCAACUCAU 22

7512 26392

CFTR- IntronlO- - AAUGAAAAAUAUCACCAACUCAU 23

7513 26393

CFTR- IntronlO- - UAAUGAAAAAUAUCACCAACUCAU 24

7514 26394

CFTR- IntronlO- - UUUGUAAAUUUGUUUCAU 18

7515 26395

CFTR- IntronlO- - UUUUGUAAAUUUGUUUCAU 19

7516 26396

CFTR-

- AUUUUGUAAAUUUGUUUCAU 20

IntronlO- 26397

1125

5535.1 7517

CFTR- IntronlO- - AAUUUUGUAAAUUUGUUUCAU 21

7518 26398

CFTR- IntronlO- - UAAUUUUGUAAAUUUGUUUCAU 22

7519 26399

CFTR- IntronlO- - CUAAUUUUGUAAAUUUGUUUCAU 23

7520 26400

CFTR- IntronlO- - ACUAAUUUUGUAAAUUUGUUUCAU 24

7521 26401

CFTR- IntronlO- - UUUAUCAAUAUCUAAGAU 18

7522 26402

CFTR- IntronlO- - AUUUAUCAAUAUCUAAGAU 19

7523 26403

CFTR- IntronlO- - UAUUUAUCAAUAUCUAAGAU 20

7524 26404

CFTR- IntronlO- - UUAUUUAUCAAUAUCUAAGAU 21

7525 26405

CFTR- IntronlO- - AUUAUUUAUCAAUAUCUAAGAU 22

7526 26406

CFTR- IntronlO- - AAUUAUUUAUCAAUAUCUAAGAU 23

7527 26407

CFTR- IntronlO- - CAAUUAUUUAUCAAUAUCUAAGAU 24

7528 26408

CFTR- IntronlO- - A AG A A U C A A A UUAGAGAU 18

7529 26409

CFTR- IntronlO- - AAAGAAUCAAAUUAGAGAU 19

7530 26410

CFTR-

- G A A AG A A U C A A A UUAGAGAU 20

IntronlO- 26411

1126

5535.1 7531

CFTR- IntronlO- - U G A A AG A A U C A A A UUAGAGAU 21

7532 26412

CFTR- IntronlO- - AUGAAAGAAUCAAAUUAGAGAU 22

7533 26413

CFTR- IntronlO- - CAUGAAAGAAUCAAAUUAGAGAU 23

7534 26414

CFTR- IntronlO- - ACAUGAAAGAAUCAAAUUAGAGAU 24

7535 26415

CFTR- IntronlO- - UUUGGAAUUUUGGGAGAU 18

7536 26416

CFTR- IntronlO- - UUUUGGAAUUUUGGGAGAU 19

7537 26417

CFTR- IntronlO- - AUUUUGGAAUUUUGGGAGAU 20

7538 26418

CFTR- IntronlO- - UAUUUUGGAAUUUUGGGAGAU 21

7539 26419

CFTR- IntronlO- - AUAUUUUGGAAUUUUGGGAGAU 22

7540 26420

CFTR- IntronlO- - AAUAUUUUGGAAUUUUGGGAGAU 23

7541 26421

CFTR- IntronlO- - CAAUAUUUUGGAAUUUUGGGAGAU 24

7542 26422

CFTR- IntronlO- - UAUUUCUCUGGGUGAGAU 18

7543 26423

CFTR- IntronlO- - UUAUUUCUCUGGGUGAGAU 19

7544 26424

CFTR-

- CUUAUUUCUCUGGGUGAGAU 20

IntronlO- 26425

1127

5535.1 7545

CFTR- IntronlO- - GCUUAUUUCUCUGGGUGAGAU 21

7546 26426

CFTR- IntronlO- - GGCUUAUUUCUCUGGGUGAGAU 22

7547 26427

CFTR- IntronlO- - AGGCUUAUUUCUCUGGGUGAGAU 23

7548 26428

CFTR- IntronlO- - AAGGCUUAUUUCUCUGGGUGAGAU 24

7549 26429

CFTR- IntronlO- - UCUGAAAAAAUAGUAGAU 18

7550 26430

CFTR- IntronlO- - AUCUGAAAAAAUAGUAGAU 19

7551 26431

CFTR- IntronlO- - CAUCUGAAAAAAUAGUAGAU 20

7552 26432

CFTR- IntronlO- - ACAUCUGAAAAAAUAGUAGAU 21

7553 26433

CFTR- IntronlO- - UACAUCUGAAAAAAUAGUAGAU 22

7554 26434

CFTR- IntronlO- - AUACAUCUGAAAAAAUAGUAGAU 23

7555 26435

CFTR- IntronlO- - GAUACAUCUGAAAAAAUAGUAGAU 24

7556 26436

CFTR- IntronlO- - UUGCAGGAGGUGAGGGAU 18

7557 26437

CFTR- IntronlO- - CUUGCAGGAGGUGAGGGAU 19

7558 26438

CFTR-

- ACUUGCAGGAGGUGAGGGAU 20

IntronlO- 26439

1128

5535.1 7559

CFTR- IntronlO- - GACUUGCAGGAGGUGAGGGAU 21

7560 26440

CFTR- IntronlO- - AGACUUGCAGGAGGUGAGGGAU 22

7561 26441

CFTR- IntronlO- - AAGACUUGCAGGAGGUGAGGGAU 23

7562 26442

CFTR- IntronlO- - AAAGACUUGCAGGAGGUGAGGGAU 24

7563 26443

CFTR- IntronlO- - A A AG G A A AG AGGGUUGAU 18

7564 26444

CFTR- IntronlO- - UAAAGGAAAGAGGGUUGAU 19

7565 26445

CFTR- IntronlO- - CUAAAGGAAAGAGGGUUGAU 20

7566 26446

CFTR- IntronlO- - UCUAAAGGAAAGAGGGUUGAU 21

7567 26447

CFTR- IntronlO- - UUCUAAAGGAAAGAGGGUUGAU 22

7568 26448

CFTR- IntronlO- - AUUCUAAAGGAAAGAGGGUUGAU 23

7569 26449

CFTR- IntronlO- - GAUUCUAAAGGAAAGAGGGUUGAU 24

7570 26450

CFTR- IntronlO- - AGUUGAACAAUGGCAUAU 18

7571 26451

CFTR- IntronlO- - AAGUUGAACAAUGGCAUAU 19

7572 26452

CFTR-

- UAAGUUGAACAAUGGCAUAU 20

IntronlO- 26453

1129

5535.1 7573

CFTR- IntronlO- - AUAAGUUGAACAAUGGCAUAU 21

7574 26454

CFTR- IntronlO- - GAUAAGUUGAACAAUGGCAUAU 22

7575 26455

CFTR- IntronlO- - GGAUAAGUUGAACAAUGGCAUAU 23

7576 26456

CFTR- IntronlO- - UGGAUAAGUUGAACAAUGGCAUAU 24

7577 26457

CFTR- IntronlO- - CAACUUAACCUGGCAUAU 18

7578 26458

CFTR- IntronlO- - ACAACUUAACCUGGCAUAU 19

7579 26459

CFTR- IntronlO- - AACAACUUAACCUGGCAUAU 20

7580 26460

CFTR- IntronlO- - GAACAACUUAACCUGGCAUAU 21

7581 26461

CFTR- IntronlO- - AGAA CAACUUAACCUGGCAUAU 22

7582 26462

CFTR- IntronlO- - AAGAACAACUUAACCUGGCAUAU 23

7583 26463

CFTR- IntronlO- - UAAGAACAACUUAACCUGGCAUAU 24

7584 26464

CFTR- IntronlO- - AU U AAAAAAU U AU ACU AU 18

7585 26465

CFTR- IntronlO- - U AU U AAAAAAU U AU ACU AU 19

7586 26466

CFTR-

- CUAUUAAAAAAUUAUACUAU 20

IntronlO- 20222

1130

5535.1 1337

CFTR- IntronlO- - ACUAUUAAAAAAUUAUACUAU 21

7587 26467

CFTR- IntronlO- - CACUAUUAAAAAAUUAUACUAU 22

7588 26468

CFTR- IntronlO- - U CACU AU U AAAAAAU U AU ACU AU 23

7589 26469

CFTR- IntronlO- - UUCACUAUUAAAAAAUUAUACUAU 24

7590 26470

CFTR- IntronlO- - UUUAUAAAGCUGUACUAU 18

7591 26471

CFTR- IntronlO- - GUUUAUAAAGCUGUACUAU 19

7592 26472

CFTR- IntronlO- - GGUUUAUAAAGCUGUACUAU 20

7593 26473

CFTR- IntronlO- - AGGUUUAUAAAGCUGUACUAU 21

7594 26474

CFTR- IntronlO- - UAGGUUUAUAAAGCUGUACUAU 22

7595 26475

CFTR- IntronlO- - UUAGGUUUAUAAAGCUGUACUAU 23

7596 26476

CFTR- IntronlO- - UUUAGGUUUAUAAAGCUGUACUAU 24

7597 26477

CFTR- IntronlO- - UAAGGGCAUUCUAAGUAU 18

7598 26478

CFTR- IntronlO- - CUAAGGGCAUUCUAAGUAU 19

7599 26479

CFTR-

- CCUAAGGGCAUUCUAAGUAU 20

IntronlO- 26480

1131

5535.1 7600

CFTR- IntronlO- - GCCUAAGGGCAUUCUAAGUAU 21

7601 26481

CFTR- IntronlO- - AGCCUAAGGGCAUUCUAAGUAU 22

7602 26482

CFTR- IntronlO- - UAGCCUAAGGGCAUUCUAAGUAU 23

7603 26483

CFTR- IntronlO- - UUAGCCUAAGGGCAUUCUAAGUAU 24

7604 26484

CFTR- IntronlO- - GCUGCCUUUUAGUAGUAU 18

7605 26485

CFTR- IntronlO- - GGCUGCCUUUUAGUAGUAU 19

7606 26486

CFTR- IntronlO- - AGGCUGCCUUUUAGUAGUAU 20

7607 26487

CFTR- IntronlO- - GAGGCUGCCUUUUAGUAGUAU 21

7608 26488

CFTR- IntronlO- - GGAGGCUGCCUUUUAGUAGUAU 22

7609 26489

CFTR- IntronlO- - AGGAGGCUGCCUUUUAGUAGUAU 23

7610 26490

CFTR- IntronlO- - UAGGAGGCUGCCUUUUAGUAGUAU 24

7611 26491

CFTR- IntronlO- - CUUUUUCAUUGAAUGUAU 18

7612 26492

CFTR- IntronlO- - UCUUUUUCAUUGAAUGUAU 19

7613 26493

CFTR-

- UUCUUUUUCAUUGAAUGUAU 20

IntronlO- 26494

1132

5535.1 7614

CFTR- IntronlO- - UUUCUUUUUCAUUGAAUGUAU 21

7615 26495

CFTR- IntronlO- - UUUUCUUUUUCAUUGAAUGUAU 22

7616 26496

CFTR- IntronlO- - CUUUUCUUUUUCAUUGAAUGUAU 23

7617 26497

CFTR- IntronlO- - CCUUUUCUUUUUCAUUGAAUGUAU 24

7618 26498

CFTR- IntronlO- - CAAUUUGGUAAUUUGUAU 18

7619 26499

CFTR- IntronlO- - ACAAUUUGGUAAUUUGUAU 19

7620 26500

CFTR- IntronlO- - UACAAUUUGGUAAUUUGUAU 20

7621 26501

CFTR- IntronlO- - AUACAAUUUGGUAAUUUGUAU 21

7622 26502

CFTR- IntronlO- - AAUACAAUUUGGUAAUUUGUAU 22

7623 26503

CFTR- IntronlO- - CAAUACAAUUUGGUAAUUUGUAU 23

7624 26504

CFTR- IntronlO- - UCAAUACAAUUUGGUAAUUUGUAU 24

7625 26505

CFTR- IntronlO- - AUUUUUAACCUGGAUUAU 18

7626 26506

CFTR- IntronlO- - UAUUUUUAACCUGGAUUAU 19

7627 26507

CFTR-

- AUAUUUUUAACCUGGAUUAU 20

IntronlO- 26508

1133

5535.1 7628

CFTR- IntronlO- - UAUAUUUUUAACCUGGAUUAU 21

7629 26509

CFTR- IntronlO- - AUAUAUUUUUAACCUGGAUUAU 22

7630 26510

CFTR- IntronlO- - UAUAUAUUUUUAACCUGGAUUAU 23

7631 26511

CFTR- IntronlO- - AUAUAUAUUUUUAACCUGGAUUAU 24

7632 26512

CFTR- IntronlO- - AAAAGUUUCUCAUCUUAU 18

7633 26513

CFTR- IntronlO- - AAAAAGUUUCUCAUCUUAU 19

7634 26514

CFTR- IntronlO- - UAAAAAGUUUCUCAUCUUAU 20

1339 20224

CFTR- IntronlO- - UUAAAAAGUUUCUCAUCUUAU 21

7635 26515

CFTR- IntronlO- - UUUAAAAAGUUUCUCAUCUUAU 22

7636 26516

CFTR- IntronlO- - AUUUAAAAAGUUUCUCAUCUUAU 23

7637 26517

CFTR- IntronlO- - AAU U U AAAAAG UUUCUCAUCUUAU 24

7638 26518

CFTR- IntronlO- - UUCCCAGCCUCCAGAACU 18

7639 26519

CFTR- IntronlO- - CUUCCCAGCCUCCAGAACU 19

7640 26520

CFTR-

- ACUUCCCAGCCUCCAGAACU 20

IntronlO- 26521

1134

5535.1 7641

CFTR- IntronlO- - GACUUCCCAGCCUCCAGAACU 21

7642 26522

CFTR- IntronlO- - GGACUUCCCAGCCUCCAGAACU 22

7643 26523

CFTR- IntronlO- - UGGACUUCCCAGCCUCCAGAACU 23

7644 26524

CFTR- IntronlO- - UUGGACUUCCCAGCCUCCAGAACU 24

7645 26525

CFTR- IntronlO- - GAUUAGGGAAUGCAGACU 18

7646 26526

CFTR- IntronlO- - GGAUUAGGGAAUGCAGACU 19

7647 26527

CFTR- IntronlO- - GGGAUUAGGGAAUGCAGACU 20

7648 26528

CFTR- IntronlO- - AGGGAUUAGGGAAUGCAGACU 21

7649 26529

CFTR- IntronlO- - GAGGGAUUAGGGAAUGCAGACU 22

7650 26530

CFTR- IntronlO- - UGAGGGAUUAGGGAAUGCAGACU 23

7651 26531

CFTR- IntronlO- - GUGAGGGAUUAGGGAAUGCAGACU 24

7652 26532

CFTR- IntronlO- - AGAAUUGAAUAUGAGACU 18

7653 26533

CFTR- IntronlO- - AAGAAUUGAAUAUGAGACU 19

7654 26534

CFTR-

- GAAGAAUUGAAUAUGAGACU 20

lntronlO-114 19000

1135

5535.1 CFTR- IntronlO- - UGAAGAAUUGAAUAUGAGACU 21

7655 26535

CFTR- IntronlO- - UUGAAGAAUUGAAUAUGAGACU 22

7656 26536

CFTR- IntronlO- - UUUGAAGAAUUGAAUAUGAGACU 23

7657 26537

CFTR- IntronlO- - UUUUGAAGAAUUGAAUAUGAGACU 24

7658 26538

CFTR- IntronlO- - UAGAUUAGCUUAUAUACU 18

7659 26539

CFTR- IntronlO- - AUAGAUUAGCUUAUAUACU 19

7660 26540

CFTR- IntronlO- - AAUAGAUUAGCUUAUAUACU 20

7661 26541

CFTR- IntronlO- - GAAUAGAUUAGCUUAUAUACU 21

7662 26542

CFTR- IntronlO- - UGAAUAGAUUAGCUUAUAUACU 22

7663 26543

CFTR- IntronlO- - UUGAAUAGAUUAGCUUAUAUACU 23

7664 26544

CFTR- IntronlO- - UUUGAAUAGAUUAGCUUAUAUACU 24

7665 26545

CFTR- IntronlO- - CCCGUAGUCCCAGCUACU 18

7666 26546

CFTR- IntronlO- - GCCCGUAGUCCCAGCUACU 19

7667 26547

CFTR- IntronlO- - UGCCCGUAGUCCCAGCUACU 20

1343 20228

1136

5535.1 CFTR- IntronlO- - GUGCCCGUAGUCCCAGCUACU 21

7668 26548

CFTR- IntronlO- - GGUGCCCGUAGUCCCAGCUACU 22

7669 26549

CFTR- IntronlO- - GGGUGCCCGUAGUCCCAGCUACU 23

7670 26550

CFTR- IntronlO- - CGGGUGCCCGUAGUCCCAGCUACU 24

7671 26551

CFTR- IntronlO- - GUGCCUGUAGUCCCAGCUACU 21

7672 26552

CFTR- IntronlO- - UGUGCCUGUAGUCCCAGCUACU 22

7673 26553

CFTR- IntronlO- - GUGUGCCUGUAGUCCCAGCUACU 23

7674 26554

CFTR- IntronlO- - UGUGUGCCUGUAGUCCCAGCUACU 24

7675 26555

CFTR- IntronlO- - UCUUUAUAAAAGAAACCU 18

7676 26556

CFTR- IntronlO- - G U CU U UAU AAAAG AAACCU 19

7677 26557

CFTR- IntronlO- - UGUCUUUAUAAAAGAAACCU 20

7678 26558

CFTR- IntronlO- - GUGUCUUUAUAAAAGAAACCU 21

7679 26559

CFTR- IntronlO- - AGUGUCUUUAUAAAAGAAACCU 22

7680 26560

CFTR- IntronlO- - UAGUGUCUU UAU AAAAG AAACCU 23

7681 26561

1137

5535.1 CFTR- IntronlO- - UUAGUGUCUUUAUAAAAGAAACCU 24

7682 26562

CFTR- IntronlO- - AGAGAGACCCUCACACCU 18

7683 26563

CFTR- IntronlO- - UAGAGAGACCCUCACACCU 19

7684 26564

CFTR- IntronlO- - UUAGAGAGACCCUCACACCU 20

7685 26565

CFTR- IntronlO- - CUUAGAGAGACCCUCACACCU 21

7686 26566

CFTR- IntronlO- - CCUUAGAGAGACCCUCACACCU 22

7687 26567

CFTR- IntronlO- - ACCUUAGAGAGACCCUCACACCU 23

7688 26568

CFTR- IntronlO- - AACCUUAGAGAGACCCUCACACCU 24

7689 26569

CFTR- IntronlO- - UUCUCCAUAUCCCACCCU 18

7690 26570

CFTR- IntronlO- - CUUCUCCAUAUCCCACCCU 19

7691 26571

CFTR- IntronlO- - UCUUCUCCAUAUCCCACCCU 20

7692 26572

CFTR- IntronlO- - CUCUUCUCCAUAUCCCACCCU 21

7693 26573

CFTR- IntronlO- - CCUCUUCUCCAUAUCCCACCCU 22

7694 26574

CFTR- IntronlO- - UCCUCUUCUCCAUAUCCCACCCU 23

7695 26575

1138

5535.1 CFTR- IntronlO- - AUCCUCUUCUCCAUAUCCCACCCU 24

7696 26576

CFTR- IntronlO- - AGGAAGGCAGUGGUCCCU 18

7697 26577

CFTR- IntronlO- - GAGGAAGGCAGUGGUCCCU 19

7698 26578

CFTR-

- AGAGGAAGGCAGUGGUCCCU 20

lntronlO-515 19401

CFTR- IntronlO- - UAGAGGAAGGCAGUGGUCCCU 21

7699 26579

CFTR- IntronlO- - UU AGAGGAAGGCAGUGGUCCCU 22

7700 26580

CFTR- IntronlO- - GUUAGAGGAAGGCAGUGGUCCCU 23

7701 26581

CFTR- IntronlO- - AGUUAGAGGAAGGCAGUGGUCCCU 24

7702 26582

CFTR- IntronlO- - GGAGGAUCACCUGAGCCU 18

7703 26583

CFTR- IntronlO- - GGGAGGAUCACCUGAGCCU 19

7704 26584

CFTR- IntronlO- - UGGGAGGAUCACCUGAGCCU 20

7705 26585

CFTR- IntronlO- - GUGGGAGGAUCACCUGAGCCU 21

7706 26586

CFTR- IntronlO- - GGUGGGAGGAUCACCUGAGCCU 22

7707 26587

CFTR- IntronlO- - AGGUGGGAGGAUCACCUGAGCCU 23

7708 26588

CFTR-

- GAGGUGGGAGGAUCACCUGAGCCU 24

IntronlO- 26589

1139

5535.1 7709

CFTR- IntronlO- - GGGUGUAGGGGUUAGCCU 18

7710 26590

CFTR- IntronlO- - GGGGUGUAGGGGUUAGCCU 19

7711 26591

CFTR- IntronlO- - AGGGGUGUAGGGGUUAGCCU 20

7712 26592

CFTR- IntronlO- - AAGGGGUGUAGGGGUUAGCCU 21

7713 26593

CFTR- IntronlO- - AAAGGGGUGUAGGGGUUAGCCU 22

7714 26594

CFTR- IntronlO- - GAAAGGGGUGUAGGGGUUAGCCU 23

7715 26595

CFTR- IntronlO- - AGAAAGGGGUGUAGGGGUUAGCCU 24

7716 26596

CFTR- IntronlO- - UAUUGCAGGGUGGGGCCU 18

7717 26597

CFTR- IntronlO- - GUAUUGCAGGGUGGGGCCU 19

7718 26598

CFTR- IntronlO- - GGUAUUGCAGGGUGGGGCCU 20

7719 26599

CFTR- IntronlO- - UGGUAUUGCAGGGUGGGGCCU 21

7720 26600

CFTR- IntronlO- - AUGGUAUUGCAGGGUGGGGCCU 22

7721 26601

CFTR- IntronlO- - GAUGGUAUUGCAGGGUGGGGCCU 23

7722 26602

CFTR-

- UGAUGGUAUUGCAGGGUGGGGCCU 24

IntronlO- 26603

1140

5535.1 7723

CFTR- IntronlO- - UUUGACCUAAGAUAUCCU 18

7724 26604

CFTR- IntronlO- - CUUUGACCUAAGAUAUCCU 19

7725 26605

CFTR- IntronlO- - UCUUUGACCUAAGAUAUCCU 20

7726 26606

CFTR- IntronlO- - CUCUUUGACCUAAGAUAUCCU 21

7727 26607

CFTR- IntronlO- - CCUCUUUGACCUAAGAUAUCCU 22

7728 26608

CFTR- IntronlO- - UCCUCUUUGACCUAAGAUAUCCU 23

7729 26609

CFTR- IntronlO- - UUCCUCUUUGACCUAAGAUAUCCU 24

7730 26610

CFTR- IntronlO- - AGCUUAUGAAAAGCAGCU 18

7731 26611

CFTR- IntronlO- - UAGCUUAUGAAAAGCAGCU 19

7732 26612

CFTR- IntronlO- - AUAGCUUAUGAAAAGCAGCU 20

7733 26613

CFTR- IntronlO- - UAUAGCUUAUGAAAAGCAGCU 21

7734 26614

CFTR- IntronlO- - UUAUAGCUUAUGAAAAGCAGCU 22

7735 26615

CFTR- IntronlO- - GUUAUAGCUUAUGAAAAGCAGCU 23

7736 26616

CFTR-

- AGUUAUAGCUUAUGAAAAGCAGCU 24

IntronlO- 26617

1141

5535.1 7737

CFTR- IntronlO- - AGAUGUGCAAAAAUAGCU 18

7738 26618

CFTR- IntronlO- - UAGAUGUGCAAAAAUAGCU 19

7739 26619

CFTR- IntronlO- - AUAGAUGUGCAAAAAUAGCU 20

7740 26620

CFTR- IntronlO- - GAUAGAUGUGCAAAAAUAGCU 21

7741 26621

CFTR- IntronlO- - UGAUAGAUGUGCAAAAAUAGCU 22

7742 26622

CFTR- IntronlO- - AUGAUAGAUGUGCAAAAAUAGCU 23

7743 26623

CFTR- IntronlO- - UAUGAUAGAUGUGCAAAAAUAGCU 24

7744 26624

CFTR- IntronlO- - UCAGAUUCAGGACAUGCU 18

7745 26625

CFTR- IntronlO- - AUCAGAUUCAGGACAUGCU 19

7746 26626

CFTR- IntronlO- - GAUCAGAUUCAGGACAUGCU 20

7747 26627

CFTR- IntronlO- - UGAUCAGAUUCAGGACAUGCU 21

7748 26628

CFTR- IntronlO- - GUGAUCAGAUUCAGGACAUGCU 22

7749 26629

CFTR- IntronlO- - AGUGAUCAGAUUCAGGACAUGCU 23

7750 26630

CFTR-

- AAGUGAUCAGAUUCAGGACAUGCU 24

IntronlO- 26631

1142

5535.1 7751

CFTR- IntronlO- - AGUUUACUAACUCAAUCU 18

7752 26632

CFTR- IntronlO- - GAGUUUACUAACUCAAUCU 19

7753 26633

CFTR-

- GGAGUUUACUAACUCAAUCU 20

lntronlO-118 19004

CFTR- IntronlO- - CGGAGUUUACUAACUCAAUCU 21

7754 26634

CFTR- IntronlO- - ACGGAGUUUACUAACUCAAUCU 22

7755 26635

CFTR- IntronlO- - AACGGAGUUUACUAACUCAAUCU 23

7756 26636

CFTR- IntronlO- - AAACGGAGUUUACUAACUCAAUCU 24

7757 26637

CFTR- IntronlO- - UUUAUCAAGUUGUUAUCU 18

7758 26638

CFTR- IntronlO- - AUUUAUCAAGUUGUUAUCU 19

7759 26639

CFTR- IntronlO- - AAUUUAUCAAGUUGUUAUCU 20

7760 26640

CFTR- IntronlO- - AAAUUUAUCAAGUUGUUAUCU 21

7761 26641

CFTR- IntronlO- - UAAAUUUAUCAAGUUGUUAUCU 22

7762 26642

CFTR- IntronlO- - AUAAAUUUAUCAAGUUGUUAUCU 23

7763 26643

CFTR- IntronlO- - GAUAAAUUUAUCAAGUUGUUAUCU 24

7764 26644

1143

5535.1 CFTR- IntronlO- - UUAGGGAAUGCAGACUCU 18

7765 26645

CFTR- IntronlO- - AUUAGGGAAUGCAGACUCU 19

7766 26646

CFTR-

- GAUUAGGGAAUGCAGACUCU 20

lntronlO-119 19005

CFTR- IntronlO- - GGAUUAGGGAAUGCAGACUCU 21

7767 26647

CFTR- IntronlO- - GGGAUUAGGGAAUGCAGACUCU 22

7768 26648

CFTR- IntronlO- - AGGGAUUAGGGAAUGCAGACUCU 23

7769 26649

CFTR- IntronlO- - GAGGGAUUAGGGAAUGCAGACUCU 24

7770 26650

CFTR- IntronlO- - CC A A U A A A A U A A A AG U C U 18

7771 26651

CFTR- IntronlO- - C CC A A U A A A A U A A A AG U C U 19

7772 26652

CFTR- IntronlO- - ACCCAAUAAAAUAAAAGUCU 20

7773 26653

CFTR- IntronlO- - AACCCAAUAAAAUAAAAGUCU 21

7774 26654

CFTR- IntronlO- - AAACCCAAUAAAAUAAAAGUCU 22

7775 26655

CFTR- IntronlO- - AAAACCCAAUAAAAUAAAAGUCU 23

7776 26656

CFTR- IntronlO- - GAAAACCCAAUAAAAUAAAAGUCU 24

7777 26657

CFTR-

- GAAUAUUUAAACACUUCU 18

IntronlO- 26658

1144

5535.1 7778

CFTR- IntronlO- - GGAAUAUUUAAACACUUCU 19

7779 26659

CFTR- IntronlO- - GGGAAUAUUUAAACACUUCU 20

7780 26660

CFTR- IntronlO- - UGGGAAUAUUUAAACACUUCU 21

7781 26661

CFTR- IntronlO- - UUGGGAAUAUUUAAACACUUCU 22

7782 26662

CFTR- IntronlO- - CUUGGGAAUAUUUAAACACUUCU 23

7783 26663

CFTR- IntronlO- - CCUUGGGAAUAUUUAAACACUUCU 24

7784 26664

CFTR- IntronlO- - ACCCAAU AAAAU AAAAG U 18

7785 26665

CFTR- IntronlO- - AACCCAAU AAAAU AAAAG U 19

7786 26666

CFTR- IntronlO- - AAACCCAAU AAAAU AAAAG U 20

7787 26667

CFTR- IntronlO- - AAAACCCAAU AAAAU AAAAG U 21

7788 26668

CFTR- IntronlO- - G AAAACCCAAU AAAAU AAAAG U 22

7789 26669

CFTR- IntronlO- - AG AAAACCCAAU AAAAU AAAAG U 23

7790 26670

CFTR- IntronlO- - AAG AAAACCCAAU AAAAU AAAAG U 24

7791 26671

CFTR-

- AUGAGGAAGAAAGGAAGU 18

IntronlO- 26672

1145

5535.1 7792

CFTR- IntronlO- - AAUGAGGAAGAAAGGAAGU 19

7793 26673

CFTR- IntronlO- - AAAUGAGGAAGAAAGGAAGU 20

1369 20253

CFTR- IntronlO- - GAAAUGAGGAAGAAAGGAAGU 21

7794 26674

CFTR- IntronlO- - GG AAAUGAGGAAGAAAGGAAGU 22

7795 26675

CFTR- IntronlO- - AGGAAAUGAGGAAGAAAGGAAGU 23

7796 26676

CFTR- IntronlO- - AAGGAAAUGAGGAAGAAAGGAAGU 24

7797 26677

CFTR- IntronlO- - G G A A AG A AG G A AG G A AG U 18

7798 26678

CFTR- IntronlO- - AGGAAAGAAGGAAGGAAGU 19

7799 26679

CFTR- IntronlO- - A AG G A A AG A AG G A AG G AAG U 20

7800 26680

CFTR- IntronlO- - GAAGGAAAGAAGGAAGGAAGU 21

7801 26681

CFTR- IntronlO- - GGAAGGAAAGAAGGAAGGAAGU 22

7802 26682

CFTR- IntronlO- - AGGAAGGAAAGAAGGAAGGAAGU 23

7803 26683

CFTR- IntronlO- - AAGGAAGGAAAGAAGGAAGGAAGU 24

7804 26684

CFTR-

- GGUUUGGGAAUAUUAAGU 18

IntronlO- 26685

1146

5535.1 7805

CFTR- IntronlO- - UGGUUUGGGAAUAUUAAGU 19

7806 26686

CFTR- IntronlO- - UUGGUUUGGGAAUAUUAAGU 20

7807 26687

CFTR- IntronlO- - CUUGGUUUGGGAAUAUUAAGU 21

7808 26688

CFTR- IntronlO- - GCUUGGUUUGGGAAUAUUAAGU 22

7809 26689

CFTR- IntronlO- - AGCUUGGUUUGGGAAUAUUAAGU 23

7810 26690

CFTR- IntronlO- - GAGCUUGGUUUGGGAAUAUUAAGU 24

7811 26691

CFTR- IntronlO- - UCUGGUUUGAAGAACAGU 18

7812 26692

CFTR- IntronlO- - GUCUGGUUUGAAGAACAGU 19

7813 26693

CFTR- IntronlO- - UGUCUGGUUUGAAGAACAGU 20

7814 26694

CFTR- IntronlO- - CUGUCUGGUUUGAAGAACAGU 21

7815 26695

CFTR- IntronlO- - CCUGUCUGGUUUGAAGAACAGU 22

7816 26696

CFTR- IntronlO- - ACCUGUCUGGUUUGAAGAACAGU 23

7817 26697

CFTR- IntronlO- - UACCUGUCUGGUUUGAAGAACAGU 24

7818 26698

CFTR-

- CAGCUAUGAAGGCAGAGU 18

IntronlO- 26699

1147

5535.1 7819

CFTR- IntronlO- - GCAGCUAUGAAGGCAGAGU 19

7820 26700

CFTR- IntronlO- - AGCAGCUAUGAAGGCAGAGU 20

7821 26701

CFTR- IntronlO- - AAGCAGCUAUGAAGGCAGAGU 21

7822 26702

CFTR- IntronlO- - AAAGCAGCUAUGAAGGCAGAGU 22

7823 26703

CFTR- IntronlO- - A A A AG CAGCUAUGAAGGCAGAGU 23

7824 26704

CFTR- IntronlO- - GAAAAGCAGCUAUGAAGGCAGAGU 24

7825 26705

CFTR- IntronlO- - UUGCUUGAGUCCAGGAGU 18

7826 26706

CFTR- IntronlO- - AUUGCUUGAGUCCAGGAGU 19

7827 26707

CFTR- IntronlO- - AAUUGCUUGAGUCCAGGAGU 20

7828 26708

CFTR- IntronlO- - GAAUUGCUUGAGUCCAGGAGU 21

7829 26709

CFTR- IntronlO- - UGAAUUGCUUGAGUCCAGGAGU 22

7830 26710

CFTR- IntronlO- - GUGAAUUGCUUGAGUCCAGGAGU 23

7831 26711

CFTR- IntronlO- - GGUGAAUUGCUUGAGUCCAGGAGU 24

7832 26712

CFTR-

- GGAAGCAAGGAGAUGAGU 18

IntronlO- 26713

1148

5535.1 7833

CFTR- IntronlO- - AGGAAGCAAGGAGAUGAGU 19

7834 26714

CFTR- IntronlO- - GAGGAAGCAAGGAGAUGAGU 20

7835 26715

CFTR- IntronlO- - GGAGGAAGCAAGGAGAUGAGU 21

7836 26716

CFTR- IntronlO- - GGGAGGAAGCAAGGAGAUGAGU 22

7837 26717

CFTR- IntronlO- - AGGGAGGAAGCAAGGAGAUGAGU 23

7838 26718

CFTR- IntronlO- - AAGGGAGGAAGCAAGGAGAUGAGU 24

7839 26719

CFTR- IntronlO- - UAGUGGAAGUAGUAUAGU 18

7840 26720

CFTR- IntronlO- - GUAGUGGAAGUAGUAUAGU 19

7841 26721

CFTR-

- AGUAGUGGAAGUAGUAUAGU 20

lntronlO-533 19419

CFTR- IntronlO- - UAGUAGUGGAAGUAGUAUAGU 21

7842 26722

CFTR- IntronlO- - GUAGUAGUGGAAGUAGUAUAGU 22

7843 26723

CFTR- IntronlO- - GGUAGUAGUGGAAGUAGUAUAGU 23

7844 26724

CFTR- IntronlO- - AGGUAGUAGUGGAAGUAGUAUAGU 24

7845 26725

CFTR- IntronlO- - GAAGAGGGGGCUGGUAGU 18

7846 26726

1149

5535.1 CFTR- IntronlO- - GGAAGAGGGGGCUGGUAGU 19

7847 26727

CFTR- IntronlO- - AGGAAGAGGGGGCUGGUAGU 20

7848 26728

CFTR- IntronlO- - AAGGAAGAGGGGGCUGGUAGU 21

7849 26729

CFTR- IntronlO- - CAAGGAAGAGGGGGCUGGUAGU 22

7850 26730

CFTR- IntronlO- - UCAAGGAAGAGGGGGCUGGUAGU 23

7851 26731

CFTR- IntronlO- - UUCAAGGAAGAGGGGGCUGGUAGU 24

7852 26732

CFTR- IntronlO- - GAUGCUAAUCAUCUCCGU 18

7853 26733

CFTR- IntronlO- - UGAUGCUAAUCAUCUCCGU 19

7854 26734

CFTR- IntronlO- - GUGAUGCUAAUCAUCUCCGU 20

7855 26735

CFTR- IntronlO- - CGUGAUGCUAAUCAUCUCCGU 21

7856 26736

CFTR- IntronlO- - ACGUGAUGCUAAUCAUCUCCGU 22

7857 26737

CFTR- IntronlO- - CACGUGAUGCUAAUCAUCUCCGU 23

7858 26738

CFTR- IntronlO- - CCACGUGAUGCUAAUCAUCUCCGU 24

7859 26739

CFTR- IntronlO- - GCAGCUAUGCCAGCAGGU 18

7860 26740

1150

5535.1 CFTR- IntronlO- - UGCAGCUAUGCCAGCAGGU 19

7861 26741

CFTR- IntronlO- - GUGCAGCUAUGCCAGCAGGU 20

7862 26742

CFTR- IntronlO- - AGUGCAGCUAUGCCAGCAGGU 21

7863 26743

CFTR- IntronlO- - CAGUGCAGCUAUGCCAGCAGGU 22

7864 26744

CFTR- IntronlO- - UCAGUGCAGCUAUGCCAGCAGGU 23

7865 26745

CFTR- IntronlO- - AUCAGUGCAGCUAUGCCAGCAGGU 24

7866 26746

CFTR- IntronlO- - UCAGUGCUUUUUCGAGGU 18

7867 26747

CFTR- IntronlO- - AUCAGUGCUUUUUCGAGGU 19

7868 26748

CFTR- IntronlO- - AAUCAGUGCUUUUUCGAGGU 20

7869 26749

CFTR- IntronlO- - AAAUCAGUGCUUUUUCGAGGU 21

7870 26750

CFTR- IntronlO- - AAAAUCAGUGCUUUUUCGAGGU 22

7871 26751

CFTR- IntronlO- - UAAAAUCAGUGCUUUUUCGAGGU 23

7872 26752

CFTR- IntronlO- - AUAAAAUCAGUGCUUUUUCGAGGU 24

7873 26753

CFTR- IntronlO- - CAAAGACUUGCAGGAGGU 18

7874 26754

1151

5535.1 CFTR- IntronlO- - ACAAAGACUUGCAGGAGGU 19

7875 26755

CFTR- IntronlO- - AACAAAGACUUGCAGGAGGU 20

7876 26756

CFTR- IntronlO- - GAACAAAGACUUGCAGGAGGU 21

7877 26757

CFTR- IntronlO- - UGAACAAAGACUUGCAGGAGGU 22

7878 26758

CFTR- IntronlO- - U UG AACAAAG ACU UG CAGG AGG U 23

7879 26759

CFTR- IntronlO- - U U UG AACAAAG ACU UG CAGG AGG U 24

7880 26760

CFTR- IntronlO- - GUAAUCGGCGGUGGAGGU 18

7881 26761

CFTR- IntronlO- - AGUAAUCGGCGGUGGAGGU 19

7882 26762

CFTR-

- AAGUAAUCGGCGGUGGAGGU 20

lntronlO-536 19422

CFTR- IntronlO- - GAAGUAAUCGGCGGUGGAGGU 21

7883 26763

CFTR- IntronlO- - AGAAGUAAUCGGCGGUGGAGGU 22

7884 26764

CFTR- IntronlO- - GAGAAGUAAUCGGCGGUGGAGGU 23

7885 26765

CFTR- IntronlO- - AGAGAAGUAAUCGGCGGUGGAGGU 24

7886 26766

CFTR- IntronlO- - UACUUGGGAGGCUGAGGU 18

7887 26767

CFTR-

- CUACUUGGGAGGCUGAGGU 19

IntronlO- 26768

1152

5535.1 7888

CFTR-

- GCUACUUGGGAGGCUGAGGU 20

lntronlO-713 19599

CFTR- IntronlO- - AGCUACUUGGGAGGCUGAGGU 21

7889 26769

CFTR- IntronlO- - CAGCUACUUGGGAGGCUGAGGU 22

7890 26770

CFTR- IntronlO- - CCAGCUACUUGGGAGGCUGAGGU 23

7891 26771

CFTR- IntronlO- - CCCAGCUACUUGGGAGGCUGAGGU 24

7892 26772

CFTR- IntronlO- - AGGAGCCAAAAAUUGGGU 18

7893 26773

CFTR- IntronlO- - C AG G AG CCA A A A A U U G G G U 19

7894 26774

CFTR-

- UCAGGAGCCAAAAAUUGGGU 20

lntronlO-537 19423

CFTR- IntronlO- - UUCAGGAGCCAAAAAUUGGGU 21

7895 26775

CFTR- IntronlO- - UUUCAGGAGCCAAAAAUUGGGU 22

7896 26776

CFTR- IntronlO- - CUUUCAGGAGCCAAAAAUUGGGU 23

7897 26777

CFTR- IntronlO- - GCUUUCAGGAGCCAAAAAUUGGGU 24

7898 26778

CFTR- IntronlO- - UGACUAUACCUGUCUGGU 18

7899 26779

CFTR- IntronlO- - CUGACUAUACCUGUCUGGU 19

7900 26780

1153

5535.1 CFTR- IntronlO- - ACUGACUAUACCUGUCUGGU 20

7901 26781

CFTR- IntronlO- - GACUGACUAUACCUGUCUGGU 21

7902 26782

CFTR- IntronlO- - GGACUGACUAUACCUGUCUGGU 22

7903 26783

CFTR- IntronlO- - GGGACUGACUAUACCUGUCUGGU 23

7904 26784

CFTR- IntronlO- - UGGGACUGACUAUACCUGUCUGGU 24

7905 26785

CFTR- IntronlO- - UUUUGGAUGGAGCUUGGU 18

7906 26786

CFTR- IntronlO- - GUUUUGGAUGGAGCUUGGU 19

7907 26787

CFTR- IntronlO- - GGUUUUGGAUGGAGCUUGGU 20

7908 26788

CFTR- IntronlO- - AGGUUUUGGAUGGAGCUUGGU 21

7909 26789

CFTR- IntronlO- - CAGGUUUUGGAUGGAGCUUGGU 22

7910 26790

CFTR- IntronlO- - ACAGGUUUUGGAUGGAGCUUGGU 23

7911 26791

CFTR- IntronlO- - AACAGGUUUUGGAUGGAGCUUGGU 24

7912 26792

CFTR- IntronlO- - GGUACUUUGUAGAAAUGU 18

7913 26793

CFTR- IntronlO- - UGGUACUUUGUAGAAAUGU 19

7914 26794

1154

5535.1 CFTR- IntronlO- - GUGGUACUUUGUAGAAAUGU 20

7915 26795

CFTR- IntronlO- - UGUGGUACUUUGUAGAAAUGU 21

7916 26796

CFTR- IntronlO- - CUGUGGUACUUUGUAGAAAUGU 22

7917 26797

CFTR- IntronlO- - GCUGUGGUACUUUGUAGAAAUGU 23

7918 26798

CFTR- IntronlO- - AGCUGUGGUACUUUGUAGAAAUGU 24

7919 26799

CFTR- IntronlO- - CACCCCUUUCUGCCAUGU 18

7920 26800

CFTR- IntronlO- - UCACCCCUUUCUGCCAUGU 19

7921 26801

CFTR- IntronlO- - CUCACCCCUUUCUGCCAUGU 20

7922 26802

CFTR- IntronlO- - CCUCACCCCUUUCUGCCAUGU 21

7923 26803

CFTR- IntronlO- - CCCUCACCCCUUUCUGCCAUGU 22

7924 26804

CFTR- IntronlO- - ACCCUCACCCCUUUCUGCCAUGU 23

7925 26805

CFTR- IntronlO- - GACCCUCACCCCUUUCUGCCAUGU 24

7926 26806

CFTR- IntronlO- - CCCAGCCUCCAGAACUGU 18

7927 26807

CFTR- IntronlO- - UCCCAGCCUCCAGAACUGU 19

7928 26808

1155

5535.1 CFTR- IntronlO- - UUCCCAGCCUCCAGAACUGU 20

7929 26809

CFTR- IntronlO- - CUUCCCAGCCUCCAGAACUGU 21

7930 26810

CFTR- IntronlO- - ACUUCCCAGCCUCCAGAACUGU 22

7931 26811

CFTR- IntronlO- - GACUUCCCAGCCUCCAGAACUGU 23

7932 26812

CFTR- IntronlO- - GGACUUCCCAGCCUCCAGAACUGU 24

7933 26813

CFTR- IntronlO- - GGGAGGGUAGAAUACUGU 18

7934 26814

CFTR- IntronlO- - AGGGAGGGUAGAAUACUGU 19

7935 26815

CFTR- IntronlO- - CAGGGAGGGUAGAAUACUGU 20

7936 26816

CFTR- IntronlO- - ACAGGGAGGGUAGAAUACUGU 21

7937 26817

CFTR- IntronlO- - GACAGGGAGGGUAGAAUACUGU 22

7938 26818

CFTR- IntronlO- - AGACAGGGAGGGUAGAAUACUGU 23

7939 26819

CFTR- IntronlO- - AAGACAGGGAGGGUAGAAUACUGU 24

7940 26820

CFTR- IntronlO- - GUUUUUAGGCUAUUCUGU 18

7941 26821

CFTR- IntronlO- - UGUUUUUAGGCUAUUCUGU 19

7942 26822

1156

5535.1 CFTR-

- AUGUUUUUAGGCUAUUCUGU 20

lntronlO-541 19427

CFTR- IntronlO- - AAUGUUUUUAGGCUAUUCUGU 21

7943 26823

CFTR- IntronlO- - UAAUGUUUUUAGGCUAUUCUGU 22

7944 26824

CFTR- IntronlO- - CUAAUGUUUUUAGGCUAUUCUGU 23

7945 26825

CFTR- IntronlO- - GCUAAUGUUUUUAGGCUAUUCUGU 24

7946 26826

CFTR- IntronlO- - AUGGCAUCUCACCAGUGU 18

7947 26827

CFTR- IntronlO- - UAUGGCAUCUCACCAGUGU 19

7948 26828

CFTR- IntronlO- - UUAUGGCAUCUCACCAGUGU 20

7949 26829

CFTR- IntronlO- - CUUAUGGCAUCUCACCAGUGU 21

7950 26830

CFTR- IntronlO- - GCUUAUGGCAUCUCACCAGUGU 22

7951 26831

CFTR- IntronlO- - GGCUUAUGGCAUCUCACCAGUGU 23

7952 26832

CFTR- IntronlO- - UGGCUUAUGGCAUCUCACCAGUGU 24

7953 26833

CFTR- IntronlO- - GGCAUCUCACCAGUGUGU 18

7954 26834

CFTR- IntronlO- - UGGCAUCUCACCAGUGUGU 19

7955 26835

CFTR-

- AUGGCAUCUCACCAGUGUGU 20

lntronlO-542 19428

1157

5535.1 CFTR- IntronlO- - UAUGGCAUCUCACCAGUGUGU 21

7956 26836

CFTR- IntronlO- - UUAUGGCAUCUCACCAGUGUGU 22

7957 26837

CFTR- IntronlO- - CUUAUGGCAUCUCACCAGUGUGU 23

7958 26838

CFTR- IntronlO- - GCUUAUGGCAUCUCACCAGUGUGU 24

7959 26839

CFTR- IntronlO- - GUAUGUAUAUAUGUGUGU 18

7960 26840

CFTR- IntronlO- - UGUAUGUAUAUAUGUGUGU 19

7961 26841

CFTR- IntronlO- - AUGUAUGUAUAUAUGUGUGU 20

7962 26842

CFTR- IntronlO- - UAUGUAUGUAUAUAUGUGUGU 21

7963 26843

CFTR- IntronlO- - AUAUGUAUGUAUAUAUGUGUGU 22

7964 26844

CFTR- IntronlO- - CAUAUGUAUGUAUAUAUGUGUGU 23

7965 26845

CFTR- IntronlO- - UCAUAUGUAUGUAUAUAUGUGUGU 24

7966 26846

CFTR- IntronlO- - UCUAACUUUUCUUAUUGU 18

7967 26847

CFTR- IntronlO- - UUCUAACUUUUCUUAUUGU 19

7968 26848

CFTR- IntronlO- - CUUCUAACUUUUCUUAUUGU 20

7969 26849

1158

5535.1 CFTR- IntronlO- - ACUUCUAACUUUUCUUAUUGU 21

7970 26850

CFTR- IntronlO- - UACUUCUAACUUUUCUUAUUGU 22

7971 26851

CFTR- IntronlO- - UUACUUCUAACUUUUCUUAUUGU 23

7972 26852

CFTR- IntronlO- - UUUACUUCUAACUUUUCUUAUUGU 24

7973 26853

CFTR- IntronlO- - GGACCAAAACUUUAUUGU 18

7974 26854

CFTR- IntronlO- - AGGACCAAAACUUUAUUGU 19

7975 26855

CFTR- IntronlO- - AAGGACCAAAACUUUAUUGU 20

7976 26856

CFTR- IntronlO- - AAAGG ACCAAAACU U U AU UG U 21

7977 26857

CFTR- IntronlO- - AAAAGG ACCAAAACU U U AU UG U 22

7978 26858

CFTR- IntronlO- - CAAAAGGACCAAAACUUUAUUGU 23

7979 26859

CFTR- IntronlO- - GCAAAAGGACCAAAACUUUAUUGU 24

7980 26860

CFTR- IntronlO- - U ACCCAAU AAAAAAAAU U 18

7981 26861

CFTR- IntronlO- - U U ACCCAAU AAAAAAAAU U 19

7982 26862

CFTR-

- G U U ACCCAAU AAAAAAAAU U 20

lntronlO-124 19010

CFTR-

- UG U U ACCCAAU AAAAAAAAU U 21

IntronlO- 26863

1159

5535.1 7983

CFTR- IntronlO- - U UG U U ACCCAAU AAAAAAAAU U 22

7984 26864

CFTR- IntronlO- - AU UG U U ACCCAAU AAAAAAAAU U 23

7985 26865

CFTR- IntronlO- - U AU UG U U ACCCAAU AAAAAAAAU U 24

7986 26866

CFTR- IntronlO- - AG AAAU ACCG AG AAAAU U 18

7987 26867

CFTR- IntronlO- - U AG AAAU ACCG AG AAAAU U 19

7988 26868

CFTR- IntronlO- - CU AG AAAU ACCGAG AAAAU U 20

7989 26869

CFTR- IntronlO- - CCU AGAAAUACCGAG AAAAU U 21

7990 26870

CFTR- IntronlO- - GCCU AG AAAU ACCG AGAAAAUU 22

7991 26871

CFTR- IntronlO- - AGCCUAGAAAUACCGAGAAAAUU 23

7992 26872

CFTR- IntronlO- - UAGCCUAGAAAUACCGAGAAAAUU 24

7993 26873

CFTR- IntronlO- - U UAAUG AAAAU AG AAAU U 18

7994 26874

CFTR- IntronlO- - GUUAAUGAAAAUAGAAAUU 19

7995 26875

CFTR- IntronlO- - UGUUAAUGAAAAUAGAAAUU 20

7996 26876

CFTR-

- AUGUUAAUGAAAAUAGAAAUU 21

IntronlO- 26877

1160

5535.1 7997

CFTR- IntronlO- - AAUG U U AAUG AAAAU AG AAAU U 22

7998 26878

CFTR- IntronlO- - AAAUGUUAAUGAAAAUAGAAAUU 23

7999 26879

CFTR- IntronlO- - AAAAUG U U AAUG AAAAU AG AAAU U 24

8000 26880

CFTR- IntronlO- - CUACAGUUGCCUGCAAUU 18

8001 26881

CFTR- IntronlO- - GCUACAGUUGCCUGCAAUU 19

8002 26882

CFTR- IntronlO- - AGCUACAGUUGCCUGCAAUU 20

8003 26883

CFTR- IntronlO- - CAGCUACAGUUGCCUGCAAUU 21

8004 26884

CFTR- IntronlO- - GCAGCUACAGUUGCCUGCAAUU 22

8005 26885

CFTR- IntronlO- - UGCAGCUACAGUUGCCUGCAAUU 23

8006 26886

CFTR- IntronlO- - CUGCAGCUACAGUUGCCUGCAAUU 24

8007 26887

CFTR- IntronlO- - UAUCAAUAUUUUGGAAUU 18

8008 26888

CFTR- IntronlO- - UUAUCAAUAUUUUGGAAUU 19

8009 26889

CFTR- IntronlO- - UUUAUCAAUAUUUUGGAAUU 20

8010 26890

CFTR-

- UUUUAUCAAUAUUUUGGAAUU 21

IntronlO- 26891

1161

5535.1 8011

CFTR- IntronlO- - GUUUUAUCAAUAUUUUGGAAUU 22

8012 26892

CFTR- IntronlO- - AGUUUUAUCAAUAUUUUGGAAUU 23

8013 26893

CFTR- IntronlO- - UAGUUUUAUCAAUAUUUUGGAAUU 24

8014 26894

CFTR- IntronlO- - GGUACUACUGUAAUAAUU 18

8015 26895

CFTR- IntronlO- - UGGUACUACUGUAAUAAUU 19

8016 26896

CFTR- IntronlO- - AUGGUACUACUGUAAUAAUU 20

1381 20265

CFTR- IntronlO- - UAUGGUACUACUGUAAUAAUU 21

8017 26897

CFTR- IntronlO- - AUAUGGUACUACUGUAAUAAUU 22

8018 26898

CFTR- IntronlO- - CAUAUGGUACUACUGUAAUAAUU 23

8019 26899

CFTR- IntronlO- - ACAUAUGGUACUACUGUAAUAAUU 24

8020 26900

CFTR- IntronlO- - AAAUAUCACCAACUCAUU 18

8021 26901

CFTR- IntronlO- - AAAAUAUCACCAACUCAUU 19

8022 26902

CFTR-

- AAAAAUAUCACCAACUCAUU 20

lntronlO-544 19430

CFTR- IntronlO- - GAAAAAUAUCACCAACUCAUU 21

8023 26903

1162

5535.1 CFTR- IntronlO- - UGAAAAAUAUCACCAACUCAUU 22

8024 26904

CFTR- IntronlO- - AUGAAAAAUAUCACCAACUCAUU 23

8025 26905

CFTR- IntronlO- - AAUGAAAAAUAUCACCAACUCAUU 24

8026 26906

CFTR- IntronlO- - GUAGGAAGUGAUCAGAUU 18

8027 26907

CFTR- IntronlO- - AGUAGGAAGUGAUCAGAUU 19

8028 26908

CFTR- IntronlO- - UAGUAGGAAGUGAUCAGAUU 20

8029 26909

CFTR- IntronlO- - AUAGUAGGAAGUGAUCAGAUU 21

8030 26910

CFTR- IntronlO- - UAUAGUAGGAAGUGAUCAGAUU 22

8031 26911

CFTR- IntronlO- - GUAUAGUAGGAAGUGAUCAGAUU 23

8032 26912

CFTR- IntronlO- - AG U AU AG U AGG AAG UG AU CAG AU U 24

8033 26913

CFTR- IntronlO- - AGCUGGCUAUCCAGGAUU 18

8034 26914

CFTR- IntronlO- - CAGCUGGCUAUCCAGGAUU 19

8035 26915

CFTR- IntronlO- - ACAGCUGGCUAUCCAGGAUU 20

8036 26916

CFTR- IntronlO- - GACAGCUGGCUAUCCAGGAUU 21

8037 26917

1163

5535.1 CFTR- IntronlO- - AGACAGCUGGCUAUCCAGGAUU 22

8038 26918

CFTR- IntronlO- - AAGACAGCUGGCUAUCCAGGAUU 23

8039 26919

CFTR- IntronlO- - GAAGACAGCUGGCUAUCCAGGAUU 24

8040 26920

CFTR- IntronlO- - UGCAGGAGGUGAGGGAUU 18

8041 26921

CFTR- IntronlO- - UUGCAGGAGGUGAGGGAUU 19

8042 26922

CFTR- IntronlO- - CUUGCAGGAGGUGAGGGAUU 20

1384 20268

CFTR- IntronlO- - ACUUGCAGGAGGUGAGGGAUU 21

8043 26923

CFTR- IntronlO- - GACU UGCAGGAGGUGAGGGAUU 22

8044 26924

CFTR- IntronlO- - AGACUUGCAGGAGGUGAGGGAUU 23

8045 26925

CFTR- IntronlO- - AAGACUUGCAGGAGGUGAGGGAUU 24

8046 26926

CFTR- IntronlO- - AAUAGUUUUAUCAAUAUU 18

8047 26927

CFTR- IntronlO- - AAAU AG UUUUAUCAAUAUU 19

8048 26928

CFTR- IntronlO- - CAAAUAGUUUUAUCAAUAUU 20

8049 26929

CFTR- IntronlO- - GCAAAUAGUUUUAUCAAUAUU 21

8050 26930

1164

5535.1 CFTR- IntronlO- - UGCAAAUAGUUUUAUCAAUAUU 22

8051 26931

CFTR- IntronlO- - CUGCAAAUAGUUUUAUCAAUAUU 23

8052 26932

CFTR- IntronlO- - UCUGCAAAUAGUUUUAUCAAUAUU 24

8053 26933

CFTR- IntronlO- - G AUG AGG AGAACCAU AU U 18

8054 26934

CFTR- IntronlO- - AGAUGAGGAGAACCAUAUU 19

8055 26935

CFTR- IntronlO- - AAGAUGAGGAGAACCAUAUU 20

8056 26936

CFTR- IntronlO- - UAAGAUGAGGAGAACCAUAUU 21

8057 26937

CFTR- IntronlO- - CUAAGAUGAGGAGAACCAUAUU 22

8058 26938

CFTR- IntronlO- - UCUAAGAUGAGGAGAACCAUAUU 23

8059 26939

CFTR- IntronlO- - AUCUAAGAUGAGGAGAACCAUAUU 24

8060 26940

CFTR- IntronlO- - AACUUAACCUGGCAUAUU 18

8061 26941

CFTR- IntronlO- - CAACUUAACCUGGCAUAUU 19

8062 26942

CFTR-

- ACAACUUAACCUGGCAUAUU 20

lntronlO-546 19432

CFTR- IntronlO- - AACAACUUAACCUGGCAUAUU 21

8063 26943

CFTR-

- GAACAACUUAACCUGGCAUAUU 22

IntronlO- 26944

1165

5535.1 8064

CFTR- IntronlO- - AGAACAACUUAACCUGGCAUAUU 23

8065 26945

CFTR- IntronlO- - AAGAACAACUUAACCUGGCAUAUU 24

8066 26946

CFTR- IntronlO- - UGCUCUCUUUUAACUAUU 18

8067 26947

CFTR- IntronlO- - UUGCUCUCUUUUAACUAUU 19

8068 26948

CFTR- IntronlO- - CUUGCUCUCUUUUAACUAUU 20

8069 26949

CFTR- IntronlO- - ACUUGCUCUCUUUUAACUAUU 21

8070 26950

CFTR- IntronlO- - AACUUGCUCUCUUUUAACUAUU 22

8071 26951

CFTR- IntronlO- - AAACUUGCUCUCUUUUAACUAUU 23

8072 26952

CFTR- IntronlO- - AAAACUUGCUCUCUUUUAACUAUU 24

8073 26953

CFTR- IntronlO- - GUUUUUCUUUCCUUUAUU 18

8074 26954

CFTR- IntronlO- - UGUUUUUCUUUCCUUUAUU 19

8075 26955

CFTR- IntronlO- - AUGUUUUUCUUUCCUUUAUU 20

8076 26956

CFTR- IntronlO- - UAUGUUUUUCUUUCCUUUAUU 21

8077 26957

CFTR-

- UUAUGUUUUUCUUUCCUUUAUU 22

IntronlO- 26958

1166

5535.1 8078

CFTR- IntronlO- - UUUAUGUUUUUCUUUCCUUUAUU 23

8079 26959

CFTR- IntronlO- - UUUUAUGUUUUUCUUUCCUUUAUU 24

8080 26960

CFTR- IntronlO- - GGGAAUAUUUAAACACUU 18

8081 26961

CFTR- IntronlO- - UGGGAAUAUUUAAACACUU 19

8082 26962

CFTR- IntronlO- - UUGGGAAUAUUUAAACACUU 20

8083 26963

CFTR- IntronlO- - CUUGGGAAUAUUUAAACACUU 21

8084 26964

CFTR- IntronlO- - CCUUGGGAAUAUUUAAACACUU 22

8085 26965

CFTR- IntronlO- - CCCUUGGGAAUAUUUAAACACUU 23

8086 26966

CFTR- IntronlO- - UCCCUUGGGAAUAUUUAAACACUU 24

8087 26967

CFTR- IntronlO- - CUUGUAAUCCUAGCACUU 18

8088 26968

CFTR- IntronlO- - ACUUGUAAUCCUAGCACUU 19

8089 26969

CFTR- IntronlO- - CACUUGUAAUCCUAGCACUU 20

8090 26970

CFTR- IntronlO- - ACACUUGUAAUCCUAGCACUU 21

8091 26971

CFTR-

- CACACUUGUAAUCCUAGCACUU 22

IntronlO- 26972

1167

5535.1 8092

CFTR- IntronlO- - UCACACUUGUAAUCCUAGCACUU 23

8093 26973

CFTR- IntronlO- - CUCACACUUGUAAUCCUAGCACUU 24

8094 26974

CFTR- IntronlO- - GAAUUGAAUAUGAGACUU 18

8095 26975

CFTR- IntronlO- - AGAAUUGAAUAUGAGACUU 19

8096 26976

CFTR- IntronlO- - AAGAAUUGAAUAUGAGACUU 20

1394 20278

CFTR- IntronlO- - GAAGAAUUGAAUAUGAGACUU 21

8097 26977

CFTR- IntronlO- - UGAAGAAUUGAAUAUGAGACUU 22

8098 26978

CFTR- IntronlO- - UUGAAGAAUUGAAUAUGAGACUU 23

8099 26979

CFTR- IntronlO- - UUUGAAGAAUUGAAUAUGAGACUU 24

8100 26980

CFTR- IntronlO- - UGUGCCUGUAGUCCCAGCUACUU 23

8101 26981

CFTR- IntronlO- - GUGUGCCUGUAGUCCCAGCUACUU 24

8102 26982

CFTR- IntronlO- - AUUGCAGGGUGGGGCCUU 18

8103 26983

CFTR- IntronlO- - UAUUGCAGGGUGGGGCCUU 19

8104 26984

CFTR-

- GU AUUGCAGGGUGGGGCCUU 20

lntronlO-721 19607

1168

5535.1 CFTR- IntronlO- - GGUAUUGCAGGGUGGGGCCUU 21

8105 26985

CFTR- IntronlO- - UGGUAUUGCAGGGUGGGGCCUU 22

8106 26986

CFTR- IntronlO- - AUGGUAUUGCAGGGUGGGGCCUU 23

8107 26987

CFTR- IntronlO- - GAUGGUAUUGCAGGGUGGGGCCUU 24

8108 26988

CFTR- IntronlO- - ACAGUGCAGUUAUAGCUU 18

8109 26989

CFTR- IntronlO- - GACAGUGCAGUUAUAGCUU 19

8110 26990

CFTR- IntronlO- - UGACAGUGCAGUUAUAGCUU 20

8111 26991

CFTR- IntronlO- - CUGACAGUGCAGUUAUAGCUU 21

8112 26992

CFTR- IntronlO- - GCUGACAGUGCAGUUAUAGCUU 22

8113 26993

CFTR- IntronlO- - GGCUGACAGUGCAGUUAUAGCUU 23

8114 26994

CFTR- IntronlO- - UGGCUGACAGUGCAGUUAUAGCUU 24

8115 26995

CFTR- IntronlO- - AUUAAAUGUCUUGCGCUU 18

8116 26996

CFTR- IntronlO- - CAUUAAAUGUCUUGCGCUU 19

8117 26997

CFTR- IntronlO- - ACAUUAAAUGUCUUGCGCUU 20

8118 26998

1169

5535.1 CFTR- IntronlO- - UACAUUAAAUGUCUUGCGCUU 21

8119 26999

CFTR- IntronlO- - CUACAUUAAAUGUCUUGCGCUU 22

8120 27000

CFTR- IntronlO- - UCUACAUUAAAUGUCUUGCGCUU 23

8121 27001

CFTR- IntronlO- - GUCUACAUUAAAUGUCUUGCGCUU 24

8122 27002

CFTR- IntronlO- - GGCAAUAGGUAUUUGCUU 18

8123 27003

CFTR- IntronlO- - GGGCAAUAGGUAUUUGCUU 19

8124 27004

CFTR- IntronlO- - AGGGCAAUAGGUAUUUGCUU 20

8125 27005

CFTR- IntronlO- - AAGGGCAAUAGGUAUUUGCUU 21

8126 27006

CFTR- IntronlO- - AAAGGGCAAUAGGUAUUUGCUU 22

8127 27007

CFTR- IntronlO- - UAAAGGGCAAUAGGUAUUUGCUU 23

8128 27008

CFTR- IntronlO- - CUAAAGGGCAAUAGGUAUUUGCUU 24

8129 27009

CFTR- IntronlO- - AAUUUAACUGAAUAUCUU 18

8130 27010

CFTR- IntronlO- - AAAUUUAACUGAAUAUCUU 19

8131 27011

CFTR- IntronlO- - GAAAUUUAACUGAAUAUCUU 20

8132 27012

1170

5535.1 CFTR- IntronlO- - AGAAAUUUAACUGAAUAUCUU 21

8133 27013

CFTR- IntronlO- - UAGAAAUUUAACUGAAUAUCUU 22

8134 27014

CFTR- IntronlO- - AUAGAAAUUUAACUGAAUAUCUU 23

8135 27015

CFTR- IntronlO- - UAUAGAAAUUUAACUGAAUAUCUU 24

8136 27016

CFTR- IntronlO- - AUAAUUAACCGGUGUCUU 18

8137 27017

CFTR- IntronlO- - UAUAAUUAACCGGUGUCUU 19

8138 27018

CFTR- IntronlO- - UUAUAAUUAACCGGUGUCUU 20

8139 27019

CFTR- IntronlO- - GUUAUAAUUAACCGGUGUCUU 21

8140 27020

CFTR- IntronlO- - UGUUAUAAUUAACCGGUGUCUU 22

8141 27021

CFTR- IntronlO- - CUGUUAUAAUUAACCGGUGUCUU 23

8142 27022

CFTR- IntronlO- - ACUGUUAUAAUUAACCGGUGUCUU 24

8143 27023

CFTR- IntronlO- - UUCUAAGUAUUAGAGGUU 18

8144 27024

CFTR- IntronlO- - AUUCUAAGUAUUAGAGGUU 19

8145 27025

CFTR- IntronlO- - CAUUCUAAGUAUUAGAGGUU 20

8146 27026

1171

5535.1 CFTR- IntronlO- - GCAUUCUAAGUAUUAGAGGUU 21

8147 27027

CFTR- IntronlO- - GGCAUUCUAAGUAUUAGAGGUU 22

8148 27028

CFTR- IntronlO- - GGGCAUUCUAAGUAUUAGAGGUU 23

8149 27029

CFTR- IntronlO- - AGGGCAUUCUAAGUAUUAGAGGUU 24

8150 27030

CFTR- IntronlO- - CAGUGCUUUUUCGAGGUU 18

8151 27031

CFTR- IntronlO- - UCAGUGCUUUUUCGAGGUU 19

8152 27032

CFTR-

- AUCAGUGCUUUUUCGAGGUU 20

lntronlO-556 19442

CFTR- IntronlO- - AAUCAGUGCUUUUUCGAGGUU 21

8153 27033

CFTR- IntronlO- - AAAUCAGUGCUUUUUCGAGGUU 22

8154 27034

CFTR- IntronlO- - AAAAUCAGUGCUUUUUCGAGGUU 23

8155 27035

CFTR- IntronlO- - UAAAAUCAGUGCUUUUUCGAGGUU 24

8156 27036

CFTR- IntronlO- - UUUGGAUGGAGCUUGGUU 18

8157 27037

CFTR- IntronlO- - UUUUGGAUGGAGCUUGGUU 19

8158 27038

CFTR-

- GUUUUGGAUGGAGCUUGGUU 20

lntronlO-128 19014

CFTR- IntronlO- - GGU UUUGGAUGGAGCUUGGUU 21

8159 27039

1172

5535.1 CFTR- IntronlO- - AGGUUUUGGAUGGAGCUUGGUU 22

8160 27040

CFTR- IntronlO- - CAGGUUUUGGAUGGAGCUUGGUU 23

8161 27041

CFTR- IntronlO- - ACAGGUUUUGGAUGGAGCUUGGUU 24

8162 27042

CFTR- IntronlO- - UAAUACAUUGGAAAAUUU 18

8163 27043

CFTR- IntronlO- - UU AAU ACAU UGGAAAAUUU 19

8164 27044

CFTR- IntronlO- - GU UAAUACAUUGGAAAAUUU 20

8165 27045

CFTR- IntronlO- - AG U U AAU ACAU UGG AAAAU U U 21

8166 27046

CFTR- IntronlO- - CAG U U AAU ACAU UGG AAAAU U U 22

8167 27047

CFTR- IntronlO- - U CAG U U AAU ACAU UGG AAAAU U U 23

8168 27048

CFTR- IntronlO- - U U CAG U U AAU ACAU UGG AAAAU U U 24

8169 27049

CFTR- IntronlO- - AUCAAUAUUUUGGAAUUU 18

8170 27050

CFTR- IntronlO- - UAUCAAUAUUUUGGAAUUU 19

8171 27051

CFTR- IntronlO- - UUAUCAAUAUUUUGGAAUUU 20

1402 20286

CFTR- IntronlO- - UUUAUCAAUAUUUUGGAAUUU 21

8172 27052

1173

5535.1 CFTR- IntronlO- - UUUUAUCAAUAUUUUGGAAUUU 22

8173 27053

CFTR- IntronlO- - GUUUUAUCAAUAUUUUGGAAUUU 23

8174 27054

CFTR- IntronlO- - AGUUUUAUCAAUAUUUUGGAAUUU 24

8175 27055

CFTR- IntronlO- - UUAAUAUUACUAUUAUUU 18

8176 27056

CFTR- IntronlO- - AUUAAUAUUACUAUUAUUU 19

8177 27057

CFTR- IntronlO- - UAUUAAUAUUACUAUUAUUU 20

8178 27058

CFTR- IntronlO- - UUAUUAAUAUUACUAUUAUUU 21

8179 27059

CFTR- IntronlO- - GUUAUUAAUAUUACUAUUAUUU 22

8180 27060

CFTR- IntronlO- - UGUUAUUAAUAUUACUAUUAUUU 23

8181 27061

CFTR- IntronlO- - UUGUUAUUAAUAUUACUAUUAUUU 24

8182 27062

CFTR- IntronlO- - AAACAAGGAUGUUUAUUU 18

8183 27063

CFTR- IntronlO- - UAAACAAGGAUGUUUAUUU 19

8184 27064

CFTR- IntronlO- - CUAAACAAGGAUGUUUAUUU 20

8185 27065

CFTR- IntronlO- - UCUAAACAAGGAUGUUUAUUU 21

8186 27066

1174

5535.1 CFTR- IntronlO- - GUCUAAACAAGGAUGUUUAUUU 22

8187 27067

CFTR- IntronlO- - GGUCUAAACAAGGAUGUUUAUUU 23

8188 27068

CFTR- IntronlO- - UGGUCUAAACAAGGAUGUUUAUUU 24

8189 27069

CFTR- IntronlO- - UUGUAAUCCUAGCACUUU 18

8190 27070

CFTR- IntronlO- - CUUGUAAUCCUAGCACUUU 19

8191 27071

CFTR- IntronlO- - ACUUGUAAUCCUAGCACUUU 20

1408 20292

CFTR- IntronlO- - CACUUGUAAUCCUAGCACUUU 21

8192 27072

CFTR- IntronlO- - ACACUUGUAAUCCUAGCACUUU 22

8193 27073

CFTR- IntronlO- - CACACUUGUAAUCCUAGCACUUU 23

8194 27074

CFTR- IntronlO- - UCACACUUGUAAUCCUAGCACUUU 24

8195 27075

CFTR- IntronlO- - UUGCAGGGUGGGGCCUUU 18

8196 27076

CFTR- IntronlO- - AUUGCAGGGUGGGGCCUUU 19

8197 27077

CFTR- IntronlO- - UAUUGCAGGGUGGGGCCUUU 20

1409 20293

CFTR- IntronlO- - GU AUUGCAGGGUGGGGCCUUU 21

8198 27078

1175

5535.1 CFTR- IntronlO- - GGUAUUGCAGGGUGGGGCCUUU 22

8199 27079

CFTR- IntronlO- - UGGUAUUGCAGGGUGGGGCCUUU 23

8200 27080

CFTR- IntronlO- - AUGGUAUUGCAGGGUGGGGCCUUU 24

8201 27081

CFTR- IntronlO- - AAGAUGAUUCCAAGCUUU 18

8202 27082

CFTR- IntronlO- - AAAGAUGAUUCCAAGCUUU 19

8203 27083

CFTR- IntronlO- - CAAAGAUGAUUCCAAGCUUU 20

8204 27084

CFTR- IntronlO- - UCAAAGAUGAUUCCAAGCUUU 21

8205 27085

CFTR- IntronlO- - GUCAAAGAUGAUUCCAAGCUUU 22

8206 27086

CFTR- IntronlO- - AGUCAAAGAUGAUUCCAAGCUUU 23

8207 27087

CFTR- IntronlO- - GAGUCAAAGAUGAUUCCAAGCUUU 24

8208 27088

CFTR- IntronlO- - UCAUUAUAACACUGCUUU 18

8209 27089

CFTR- IntronlO- - UUCAUUAUAACACUGCUUU 19

8210 27090

CFTR- IntronlO- - CUUCAUUAUAACACUGCUUU 20

8211 27091

CFTR- IntronlO- - UCUUCAUUAUAACACUGCUUU 21

8212 27092

1176

5535.1 CFTR- IntronlO- - CUCUUCAUUAUAACACUGCUUU 22

8213 27093

CFTR- IntronlO- - GCUCUUCAUUAUAACACUGCUUU 23

8214 27094

CFTR- IntronlO- - AGCUCUUCAUUAUAACACUGCUUU 24

8215 27095

CFTR- IntronlO- - AUUUAACUGAAUAUCUUU 18

8216 27096

CFTR- IntronlO- - AAUUUAACUGAAUAUCUUU 19

8217 27097

CFTR- IntronlO- - AAAUUUAACUGAAUAUCUUU 20

1410 20294

CFTR- IntronlO- - GAAAUUUAACUGAAUAUCUUU 21

8218 27098

CFTR- IntronlO- - AGAAAUUUAACUGAAUAUCUUU 22

8219 27099

CFTR- IntronlO- - UAGAAAUUUAACUGAAUAUCUUU 23

8220 27100

CFTR- IntronlO- - AUAGAAAUUUAACUGAAUAUCUUU 24

8221 27101

CFTR- IntronlO- - UCAAUAUUUUGGAAUUUU 18

8222 27102

CFTR- IntronlO- - AUCAAUAUUUUGGAAUUUU 19

8223 27103

CFTR- IntronlO- - UAUCAAUAUUUUGGAAUUUU 20

1412 20296

CFTR- IntronlO- - UUAUCAAUAUUUUGGAAUUUU 21

8224 27104

1177

5535.1 CFTR- IntronlO- - UUUAUCAAUAUUUUGGAAUUUU 22

8225 27105

CFTR- IntronlO- - UUUUAUCAAUAUUUUGGAAUUUU 23

8226 27106

CFTR- IntronlO- - GUUUUAUCAAUAUUUUGGAAUUUU 24

8227 27107

CFTR- IntronlO- - GAUAAAAUCAGUGCUUUU 18

8228 27108

CFTR- IntronlO- - UGAUAAAAUCAGUGCUUUU 19

8229 27109

CFTR- IntronlO- - CUGAUAAAAUCAGUGCUUUU 20

8230 27110

CFTR- IntronlO- - UCUGAUAAAAUCAGUGCUUUU 21

8231 27111

CFTR- IntronlO- - CUCUGAUAAAAUCAGUGCUUUU 22

8232 27112

CFTR- IntronlO- - GCUCUGAUAAAAUCAGUGCUUUU 23

8233 27113

CFTR- IntronlO- - AGCUCUGAUAAAAUCAGUGCUUUU 24

8234 27114

CFTR- IntronlO- - UUAAAAUUUUAUUCUUUU 18

8235 27115

CFTR- IntronlO- - UUUAAAAUUUUAUUCUUUU 19

8236 27116

CFTR- IntronlO- - UUUUAAAAUUUUAUUCUUUU 20

8237 27117

CFTR- IntronlO- - UUUUUAAAAUUUUAUUCUUUU 21

8238 27118

1178

5535.1 CFTR- IntronlO- - AUUUUUAAAAUUUUAUUCUUUU 22

8239 27119

CFTR- IntronlO- - AAUUUUUAAAAUUUUAUUCUUUU 23

8240 27120

CFTR- IntronlO- - UAAUUUUUAAAAUUUUAUUCUUUU 24

8241 27121

CFTR- IntronlO- - AUCAUUUUGACCAUUUUU 18

8242 27122

CFTR- IntronlO- - UAUCAUUUUGACCAUUUUU 19

8243 27123

CFTR- IntronlO- - UUAUCAUUUUGACCAUUUUU 20

8244 27124

CFTR- IntronlO- - UUUAUCAUUUUGACCAUUUUU 21

8245 27125

CFTR- IntronlO- - AUUUAUCAUUUUGACCAUUUUU 22

8246 27126

CFTR- IntronlO- - AAUUUAUCAUUUUGACCAUUUUU 23

8247 27127

CFTR- IntronlO- - AAAUUUAUCAUUUUGACCAUUUUU 24

8248 27128

CFTR- IntronlO- - AUUAGUAGUUAAGUUUUU 18

8249 27129

CFTR- IntronlO- - UAUUAGUAGUUAAGUUUUU 19

8250 27130

CFTR- IntronlO- - CUAUUAGUAGUUAAGUUUUU 20

8251 27131

CFTR- IntronlO- - GCUAUUAGUAGUUAAGUUUUU 21

8252 27132

1179

5535.1 CFTR- IntronlO- - GGCUAUUAGUAGUUAAGUUUUU 22

8253 27133

CFTR- IntronlO- - AGGCUAUUAGUAGUUAAGUUUUU 23

8254 27134

CFTR- IntronlO- - UAGGCUAUUAGUAGUUAAGUUUUU 24

8255 27135

CFTR- IntronlO- - AACACUUUAUAGUUUUUU 18

8256 27136

CFTR- IntronlO- - GAACACUUUAUAGUUUUUU 19

8257 27137

CFTR- IntronlO- - GGAACACUUUAUAGUUUUUU 20

8258 27138

CFTR- IntronlO- - UGGAACACUUUAUAGUUUUUU 21

8259 27139

CFTR- IntronlO- - AUGGAACACUUUAUAGUUUUUU 22

8260 27140

CFTR- IntronlO- - AAUGGAACACUUUAUAGUUUUUU 23

8261 27141

CFTR- IntronlO- - GAAUGGAACACUUUAUAGUUUUUU 24

8262 27142

CFTR- IntronlO- - UUUUUUUUUUUUUUUUUU 18

8263 27143

CFTR- IntronlO- - uuuuuuuuuuuuuuuuuuu 19

8264 27144

CFTR- IntronlO- - uuuuuuuuuuuuuuuuuuuu 20

8265 27145

CFTR- IntronlO- - uuuuuuuuuuuuuuuuuuuuu 21

8266 27146

1180

5535.1 CFTR- IntronlO- - uuuuuuuuuuuuuuuuuuuuuu 22

8267 27147

CFTR- IntronlO- - uuuuuuuuuuuuuuuuuuuuuuu 23

8268 27148

CFTR- IntronlO- - cuuuuuuuuuuuuuuuuuuuuuuu 24

8269 27149

Table 42A provides exemplary targeting domains for correcting a mutation (e.g., 3272- 26->G) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within intron 10, have a high level of orthogonality and start with a 5'G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 42A

1181

5535.1 CFTR-lntronlO-

+ G G U AG C AG AG G AAG AAAAAG 20

8278 27158

CFTR-lntronlO-

- GCCAUACACUCUAAAUAGAG 20

8279 27159

CFTR-lntronlO-

- GUUUUCUAGAAAAUCUGUAG 20

8280 27160

CFTR-lntronlO-

- GGAGAUACAUCUGAAAAAAU 20

8281 27161

CFTR-lntronlO-

- GCAGGAAGACAGCUGGCUAU 20

8282 27162

Table 42B provides exemplary targeting domains for correcting a mutation (e.g., 3272- 26->G) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within intron 10 and have a high level of orthogonality. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through

complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 42B

1182

5535.1 8291

CFTR-lntronlO-

- AUACACUCUAAAUAGAG 17

8292 27172

CFTR-lntronlO-

- UUCUAGAAAAUCUGUAG 17

8293 27173

CFTR-lntronlO-

- AAGGCUUAUUUCUCUGG 17

8294 27174

CFTR-lntronlO-

+ CAAAUUGUAUUGAGUGG 17

8295 27175

CFTR-lntronlO-

- UAUAUAUAUGACACUAU 17

8296 27176

CFTR-lntronlO-

+ CUACUAAAAGGCAGCCU 17

8297 27177

CFTR-lntronlO-

+ UGAUCCUUU UGCAGCCU 17

8298 27178

CFTR-lntronlO-

- CUU UCCAUGAAUUAGCU 17

8299 27179

CFTR-lntronlO-

- AUUUCCAAGUAAUCUCU 17

8300 27180

CFTR-lntronlO-

- UUCGUGUAGUUUCUAUU 17

8301 27181

CFTR-lntronlO-

- AAAAG U CACAG AGG AG U CAA 20

8302 27182

CFTR-lntronlO-

+ ACAAAAGGACUAUCAGUGAA 20

8303 27183

CFTR-lntronlO-

+ UGAGUUGGUGAUAUUU UUCA 20

8304 27184

CFTR-lntronlO-

- UUAACUGAAUAUCUUUAGGA 20

8305 27185

CFTR-lntronlO-

+ AAUAAAGUAAUAGAAGCAUA 20

8306 27186

CFTR-lntronlO-

+ AAAGCUCUUUCUCAUCUCUA 20

8307 27187

CFTR-lntronlO-

+ AU AU U AAU AACAAAAU CU U A 20

3944 22826

CFTR-lntronlO-

- UCUAUGAUAUAAUGAAUCAC 20

8308 27188

CFTR-lntronlO-

- UAAAAUGGUUCCUUGUUCCC 20

8309 27189

CFTR-lntronlO-

- UGGAAACUUGUCU UCU UUUC 20

8310 27190

1183

5535.1 CFTR-lntronlO-

- UAGUGUGAAGAUGGGGCUGG 20

8311 27191

CFTR-lntronlO-

- ACUAAGGCUUAUUUCUCUGG 20

7212 26092

CFTR-lntronlO-

+ UACCAAAUUGUAUUGAGUGG 20

8312 27192

CFTR-lntronlO-

+ AUACUACUAAAAGGCAGCCU 20

8313 27193

CFTR-lntronlO-

- UAUAUUUCCAAGUAAUCUCU 20

8314 27194

CFTR-lntronlO-

+ UGUGGAGUGUAAAGGAAAUU 20

8315 27195

CFTR-lntronlO-

- AUAUUCGUGUAGUUUCUAUU 20

8316 27196

Table 42C provides exemplary targeting domains for correcting a mutation (e.g., 3272- 26->G) in the CFTR gene selected according to the third tier parameters. The targeting domains bind within intron 10 and start with a 5'G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 42C

1184

5535.1 CFTR-lntronlO-

+ GAAGAUACU A A A A A A AG U U A 20

8324 27204

CFTR-lntronlO-

- GUUGUGCAACUAUCACCUCC 20

8325 27205

CFTR-lntronlO-

- GAAGUGGAGGCUGCAGUGAG 20

8326 27206

CFTR-lntronlO-

+ GCAUCACUAGUGGCACUUUG 20

8327 27207

CFTR-lntronlO-

+ GAUAAAUUUUAACUUUUUAU 20

8328 27208

Table 42D provides exemplary targeting domains for correcting a mutation (e.g., 3272- 26->G) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within intron 10. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 42D

1185

5535.1 CFTR-lntronlO-

+ U U AAU AACAAAAU CU U A 17

8338 27218

CFTR-lntronlO-

- AUGAUAUAAUGAAUCAC 17

8339 27219

CFTR-lntronlO-

+ CACACAUAUAUACAUAC 17

8340 27220

CFTR-lntronlO-

+ UCCAAGAUCAAGGUGCC 17

8341 27221

CFTR-lntronlO-

+ C A A A U A U AAA U C A A AG C 17

8342 27222

CFTR-lntronlO-

+ AG C AG AG G A AG A A A A AG 17

8343 27223

CFTR-lntronlO-

- AAUGUUGAAUAAUAGGG 17

8344 27224

CFTR-lntronlO-

- AGGGUGGGGCCUUUGGG 17

956 19841

CFTR-lntronlO-

- UGUGAAGAUGGGGCUGG 17

8345 27225

CFTR-lntronlO-

+ CUCUGCCUCCAAAAGUG 17

8346 27226

CFTR-lntronlO-

- CUCGGCCUCCCAAAGUG 17

8347 27227

CFTR-lntronlO-

- UAGUAUAGUAGGAAGUG 17

8348 27228

CFTR-lntronlO-

+ UCACUAGUGGCACUUUG 17

8349 27229

CFTR-lntronlO-

- U CCACAAAU AU U U U U UG 17

8350 27230

CFTR-lntronlO-

- AAAGAUCUAGCU A A A A U 17

8351 27231

CFTR-lntronlO-

+ AAAUUUUAACUUUUUAU 17

8352 27232

CFTR-lntronlO-

- UU UAUUGAUACUUUUCU 17

8353 27233

CFTR-lntronlO-

- AAAGACUUGCAGGAGGU 17

8354 27234

CFTR-lntronlO-

+ UUUCUUUUUCUGU UUGU 17

8355 27235

CFTR-lntronlO-

- UGGGUAUAUUUUAUAU U 17

8356 27236

CFTR-lntronlO-

- CAGUAGUAUUAUCUUU U 17

8357 27237

1186

5535.1 CFTR-lntronlO-

- UAAAAUUUUAUUCUUUU 17

8358 27238

CFTR-lntronlO-

+ U UAUAGAGAUUACUUGGAAA 20

8359 27239

CFTR-lntronlO-

- AUACUUUGGAAUUUGUUAAA 20

8360 27240

CFTR-lntronlO-

+ ACAACCCAAAUGUCAAUCAA 20

8361 27241

CFTR-lntronlO-

+ CAAUACCAUCACCUUGGGAA 20

8362 27242

CFTR-lntronlO-

- UU UUGUAUUUAUAU UCAUAA 20

8363 27243

CFTR-lntronlO-

- UU UAUAUAGAAAUGAGGUAA 20

8364 27244

CFTR-lntronlO-

- AUGCAUAUAUAUAUUUUUAA 20

8365 27245

CFTR-lntronlO-

- AUGCUUUGAAGGAAGAUCCA 20

8366 27246

CFTR-lntronlO-

- UUGUGGAGUCAAAAAU UAUA 20

8367 27247

CFTR-lntronlO-

+ AGACACACAUAUAUACAUAC 20

8368 27248

CFTR-lntronlO-

- AACUCAUUAGGAAAAUGUAC 20

8369 27249

CFTR-lntronlO-

+ AAG U CCAAG AU CAAGG UG CC 20

8370 27250

CFTR-lntronlO-

+ A A AC A A A U A U AAA U C A A AG C 20

8371 27251

CFTR-lntronlO-

+ AUCUCCUAACCUCGAAAAAG 20

8372 27252

CFTR-lntronlO-

+ AGAGAGAACUGCUCACACGG 20

8373 27253

CFTR-lntronlO-

- AUAAAUGUUGAAUAAUAGGG 20

8374 27254

CFTR-lntronlO-

- UGCAGGGUGGGGCCUU UGGG 20

1300 20185

CFTR-lntronlO-

+ UGCCUCUGCCUCCAAAAGUG 20

8375 27255

CFTR-lntronlO-

- CGCCUCGGCCUCCCAAAGUG 20

7272 26152

CFTR-lntronlO-

- UGCCUCGGCCUCCCAAAGUG 20

7277 26157

1187

5535.1 CFTR-lntronlO-

- AAGUAGUAUAGUAGGAAGUG 20

8376 27256

CFTR-lntronlO-

- UCCUCCACAAAUAUUUUUUG 20

8377 27257

CFTR-lntronlO-

- ACAAAAGAUCUAGCUAAAAU 20

8378 27258

CFTR-lntronlO-

- ACAUAUAUAUAUGACACUAU 20

8379 27259

CFTR-lntronlO-

+ ACAUGAUCCUUUUGCAGCCU 20

8380 27260

CFTR-lntronlO-

- AAGCUUUCCAUGAAUUAGCU 20

8381 27261

CFTR-lntronlO-

- UCCUUUAUUGAUACUUUUCU 20

8382 27262

CFTR-lntronlO-

- AACAAAGACUUGCAGGAGGU 20

7876 26756

CFTR-lntronlO-

+ CUCUUUCUUUUUCUGUUUGU 20

8383 27263

CFTR-lntronlO-

- UUUUGGGUAUAUUUUAUAUU 20

8384 27264

CFTR-lntronlO-

- AGUCAGUAGUAUUAUCUUUU 20

8385 27265

CFTR-lntronlO-

- UUUUAAAAUUUUAUUCUUUU 20

8237 27117

Table 43A provides exemplary targeting domains for knocking out the SCNN1A gene selected according to the first tier parameters. The targeting domains bind within the first 500 bp of the coding sequence (e.g., with 500 bp downstream from the start codon), have a high level of orthogonality and start with a 5'G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. pyogeness Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 43A

1188

5535.1 SCNNlA-329 - GCCUCACUCGGGUUCCA 17 4178

SCNNlA-330 - GGGAGAAUGUGGGCGCA 17 4179

SCNNlA-141 + GCGGUGGAACUCGAUCA 17 551

SCNNlA-80 - GCCCAUACCAGGUCUCA 17 529

SCNNlA-106 - GCACAACCGCAUGAAGA 17 540

SCNNlA-132 + GGAGCACACCAGGCGGA 17 547

SCNNlA-121 + GUUGAUGUUGAGGCUGA 17 545

SCNNlA-331 + GGACUAACCGACCUGUA 17 4180

SCNNlA-332 - GCACCCUCAAUCCCUAC 17 4181

SCNNlA-93 - GAACAAG CG U G AG G AG C 17 533

SCNNlA-147 + GGCUGCUGGGGCGCCGC 17 554

SCNNlA-117 + GUGCAGAUGGUCACUGC 17 544

SCNNlA-333 - GAUGGGAGAGGGCACUC 17 4182

SCNNlA-107 - GCAUGAAGACGGCCUUC 17 541

SCNNlA-334 - GACAUGGGCAUGGCCAG 17 4183

SCNNlA-142 + GGCCUCCUCCUCCGCCG 17 552

SCNNlA-150 + GGGGCGCCGCAGGUUCG 17 555

SCNNlA-131 + GCUGGGAGCACACCAGG 17 546

SCNNlA-103 - GCCCACGGCGGAGGAGG 17 539

SCNNlA-102 - GCAGCCCACGGCGGAGG 17 538

SCNNlA-139 + GCUCUCGGUAGGAGCGG 17 550

SCNNlA-116 + GGUGCAGAUGGUCACUG 17 543

SCNNlA-98 - GCUGGGCCCCGAACCUG 17 535

SCNNlA-335 - GGCGCAGGGUGGGACAU 17 4184

SCNNlA-336 + GGUCAAGGCUGAGCUCU 17 4185

SCNNlA-143 + GCCUCCUCCUCCGCCGU 17 553

SCNNlA-337 - GAAUGUGGGCGCAGGGU 17 4186

SCNNlA-338 + GGGACUAACCGACCUGU 17 4187

SCNNlA-339 + GAGCCCCGGAGUGGAUU 17 4188

SCNNlA-340 - GUGGGACAUGGGCAUGGCCA 20 4189

SCNNlA-341 - GCAGCCUCACUCGGGUUCCA 20 4190

SCNNlA-342 - GAGCAGUAUCAAGGUAAGCA 20 4191

SCNNlA-15 - GGGAACAAGCGUGAGGAGCA 20 507

SCNNlA-62 + GGAGCGGUGGAACUCGAUCA 20 525

SCNNlA-343 - GUGAUGGGAGAGGGCACUCA 20 4192

SCNNlA-1 - GCAGCCCAUACCAGGUCUCA 20 503

SCNNlA-36 + GUAGGGAUUGAGGGUGCAGA 20 516

SCNNlA-76 + GCCCUGGAGUGGACUGUGGA 20 528

SCNNlA-10 - GUCCACUCCAGGGCUCAUGA 20 505

SCNNlA-42 + GAGGUUGAUGUUGAGGCUGA 20 519

SCNNlA-344 + GUAUGGGCUGCAGAGGUCUA 20 4193

SCNNlA-345 + GAGGGACUAACCGACCUGUA 20 4194

1189

5535.1 SCNNlA-32 - GCACCUUUGGCAUGAUGUAC 20 514

SCNNlA-51 + GGUUGUGCUGGGAGCACACC 20 522

SCNNlA-346 + GUGCCCUCUCCCAUCACCCC 20 4195

SCNNlA-347 - GGUGGGACAUGGGCAUGGCC 20 4196

SCNNlA-348 - GGCAGCCUCACUCGGGUUCC 20 4197

SCNNlA-176 - GCUCAUGAAGGGGAACAAGC 20 811

SCNNlA-68 + GUGGGCUGCUGGGGCGCCGC 20 526

SCNNlA-349 - GAGUGGGAGAAUGUGGGCGC 20 4198

SCNNlA-350 - GGUGAUGGGAGAGGGCACUC 20 4199

SCNNlA-351 - GGCCAGGGGCAGCCUCACUC 20 4200

SCNNlA-352 + GAUUGGGGAGAGCAAGGGUC 20 4201

SCNNlA-16 - GGAACAAGCGUGAGGAGCAG 20 508

SCNNlA-44 + GGUUGAUGUUGAGGCUGACG 20 520

SCNNlA-353 - GCUCUCCCCAAUCCACUCCG 20 4202

SCNNlA-39 + GGGUGCAGAUGGUCACUGCG 20 518

SCNNlA-71 + GCUGGGGCGCCGCAGGUUCG 20 527

SCNNlA-21 - GGCGCCCCAGCAGCCCACGG 20 510

SCNNlA-22 - GCCCCAGCAGCCCACGGCGG 20 511

SCNNlA-354 - GGGAGAAUGUGGGCGCAGGG 20 4203

SCNNlA-2 - GCCCAUACCAGGUCUCAUGG 20 497

SCNNlA-37 + GAGGGUGCAGAUGGUCACUG 20 517

SCNNlA-19 - GGGGCUGGGCCCCGAACCUG 20 509

SCNNlA-355 - GUGGGCGCAGGGUGGGACAU 20 4204

SCNNlA-356 + GGUAUGGGCUGCAGAGGUCU 20 4205

SCNNlA-58 + GAACUCGAAGAGCUCUCGGU 20 524

SCNNlA-357 - GGAGAAUGUGGGCGCAGGGU 20 4206

SCNNlA-33 - GGCAUGAUGUACUGGCAAUU 20 515

SCNNlA-31 - GUGCUGUGGCUCUGCACCUU 20 513

Table 43B provides exemplary targeting domains for knocking out the SCNN1A gene selected according to the second tier parameters. The targeting domains bind within the first 500 bp of the coding sequence (e.g., with 500 bp downstream from the start codon) and have a high level of orthogonality. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. pyogeness Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 43B

1190

5535.1 Length

SCNNlA-125 + CCAGUACAUCAUGCCAA 17 632

SCNNlA-358 - CCAGCUGUCCCUUCCAA 17 4207

SCNNlA-359 - AG U A U C A AG G U A AG C A A 17 4208

SCNNlA-90 - ACUCCAGGGCUCAUGAA 17 611

SCNNlA-360 - ACUCCGGGGCUCAUGAA 17 4209

SCNNlA-104 - AACAACACCACCAUCCA 17 617

SCNNlA-88 - CUCCACAGUCCACUCCA 17 609

SCNNlA-361 - CAGUAUCAAGGUAAGCA 17 4210

SCNNlA-94 - AACAAG CG U G AG G AG CA 17 613

SCNNlA-362 - UAUCAUGAGCAGUAUCA 17 4211

SCNNlA-363 - AUGGGAGAGGGCACUCA 17 4212

SCNNlA-126 + CCACAGCACUGCCCAGA 17 633

SCNNlA-82 - AUACCAGGUCUCAUGGA 17 501

SCNNlA-364 + UGAUACCUCCCCUUGGA 17 4213

SCNNlA-89 - CACUCCAGGGCUCAUGA 17 610

SCNNlA-365 - CACUCCGGGGCUCAUGA 17 4214

SCNNlA-366 - UCGGGUUCCAGGGGUGA 17 4215

SCNNlA-367 + CGACCUGUAGGGAUUGA 17 4216

SCNNlA-157 + CUCCAUGAGACCUGGUA 17 502

SCNNlA-122 + UUGAUGUUGAGGCUGAC 17 629

SCNNlA-111 - CCUUUGGCAUGAUGUAC 17 622

SCNNlA-130 + UGUGCUGGGAGCACACC 17 637

SCNNlA-156 + UUCCCCUCCAUGAGACC 17 653

SCNNlA-368 - CCUCUGCAGCCCAUACC 17 4217

SCNNlA-369 + CCGAGUGAGGCUGCCCC 17 4218

SCNNlA-370 - UCUCCCCAAUCCACUCC 17 4219

SCNNlA-87 - CCUCCACAGUCCACUCC 17 608

SCNNlA-371 - AGCCUCACUCGGGUUCC 17 4220

SCNNlA-124 + AGUACUCUCCGAAAAGC 17 631

SCNNlA-260 - C A U G A AG G G G AACAAG C 17 868

SCNNlA-84 - CAUGGAGGGGAACAAGC 17 607

SCNNlA-372 + CCCUUGGAAGGGACAGC 17 4221

SCNNlA-373 - UGGGAGAAUGUGGGCGC 17 4222

SCNNlA-144 + CCUCCGCCGUGGGCUGC 17 643

SCNNlA-128 + UCUUCAUGCGGUUGUGC 17 635

SCNNlA-140 + AGCGGUGGAACUCGAUC 17 642

SCNNlA-374 - CUCUCCCCAAUCCACUC 17 4223

SCNNlA-375 - CAGGGGCAGCCUCACUC 17 4224

SCNNlA-376 + UGGGGAGAGCAAGGGUC 17 4225

SCNNlA-149 + UGGGGCGCCGCAGGUUC 17 647

SCNNlA-377 - CAGCUGUCCCUUCCAAG 17 4226

1191

5535.1 SCNNlA-91 - CUCCAGGGCUCAUGAAG 17 612

SCNNlA-378 - CUCCGGGGCUCAUGAAG 17 4227

SCNNlA-379 - CCUCACUCGGGUUCCAG 17 4228

SCNNlA-95 - ACAAGCGUGAGGAGCAG 17 614

SCNNlA-380 + CCUGGUAUGGGCUGCAG 17 4229

SCNNlA-138 + AGAGCUCUCGGUAGGAG 17 641

SCNNlA-381 + CUUCAUGAGCCCCGGAG 17 4230

SCNNlA-152 + CUUCAUGAGCCCUGGAG 17 649

SCNNlA-123 + UGAUGUUGAGGCUGACG 17 630

SCNNlA-382 - CUCCCCAAUCCACUCCG 17 4231

SCNNlA-118 + UGCAGAUGGUCACUGCG 17 626

SCNNlA-101 - CCAGCAGCCCACGGCGG 17 616

SCNNlA-383 - AGAAUGUGGGCGCAGGG 17 4232

SCNNlA-384 - CUGUCCCUUCCAAGGGG 17 4233

SCNNlA-81 - CAUACCAGGUCUCAUGG 17 605

SCNNlA-127 + AGAAGGCCGUCUUCAUG 17 634

SCNNlA-146 + UCCGCCGUGGGCUGCUG 17 645

SCNNlA-385 + CCCCUGGAACCCGAGUG 17 4234

SCNNlA-386 + CCGACCUGUAGGGAUUG 17 4235

SCNNlA-387 + AGCCCCGGAGUGGAUUG 17 4236

SCNNlA-119 + CGAGCUUGUCCGAGUUG 17 627

SCNNlA-120 + AGUUGAGGUUGAUGUUG 17 628

SCNNlA-388 + UGAGCCCCGGAGUGGAU 17 4237

SCNNlA-389 - CGGGUUCCAGGGGUGAU 17 4238

SCNNlA-158 + UCCAUGAGACCUGGUAU 17 654

SCNNlA-114 - CAACAUCAACCUCAACU 17 625

SCNNlA-97 - CGUGAGGAGCAGGGGCU 17 615

SCNNlA-145 + CUCCGCCGUGGGCUGCU 17 644

SCNNlA-129 + CUUCAUGCGGUUGUGCU 17 636

SCNNlA-136 + AGAACUCGAAGAGCUCU 17 639

SCNNlA-390 + AUGGGCUGCAGAGGUCU 17 4239

SCNNlA-108 - CAUGAAGACGGCCUUCU 17 619

SCNNlA-391 - CCUCAAUCCCUACAGGU 17 4240

SCNNlA-137 + CUCGAAGAGCUCUCGGU 17 640

SCNNlA-112 - AUGAUGUACUGGCAAUU 17 623

SCNNlA-110 - CUGUGGCUCUGCACCUU 17 621

SCNNlA-148 + CUGGGGCGCCGCAGGUU 17 646

SCNNlA-392 - AGCAAGGGAACCUGGUU 17 4241

SCNNlA-113 - CAAUUCGGCCUGCUUUU 17 624

SCNNlA-46 + UUGCCAGUACAUCAUGCCAA 20 580

SCNNlA-393 - AGCAGUAUCAAGGUAAGCAA 20 4242

SCNNlA-394 + CAUGAUACCUCCCCUUGGAA 20 4243

1192

5535.1 SCNNlA-395 - UGUGGGCGCAGGGUGGGACA 20 4244

SCNNlA-20 - UGCGGCGCCCCAGCAGCCCA 20 565

SCNNlA-25 - UGCAACAACACCACCAUCCA 20 567

SCNNlA-396 - AGUGGGAGAAUGUGGGCGCA 20 4245

SCNNlA-397 - AGGUAUCAUGAGCAGUAUCA 20 4246

SCNNlA-398 + AUUGGGGAGAGCAAGGGUCA 20 4247

SCNNlA-27 - CCAGCACAACCGCAUGAAGA 20 569

SCNNlA-53 + CUGGGAGCACACCAGGCGGA 20 585

SCNNlA-3 - CCCAUACCAGGUCUCAUGGA 20 556

SCNNlA-399 + UCAUGAUACCUCCCCUUGGA 20 4248

SCNNlA-400 - AUCCACUCCGGGGCUCAUGA 20 4249

SCNNlA-401 - CACUCGGGUUCCAGGGGUGA 20 4250

SCNNlA-402 + AACCGACCUGUAGGGAUUGA 20 4251

SCNNlA-78 + CCCCUCCAUGAGACCUGGUA 20 500

SCNNlA-43 + AGGUUGAUGUUGAGGCUGAC 20 578

SCNNlA-403 - UCUGCACCCUCAAUCCCUAC 20 4252

SCNNlA-404 - U C A AG G U A AG C A AG G G A AC C 20 4253

SCNNlA-405 - AGACCUCUGCAGCCCAUACC 20 4254

SCNNlA-406 + AACCCGAGUGAGGCUGCCCC 20 4255

SCNNlA-407 - UAGUCCCUCUGCCCCUUCCC 20 4256

SCNNlA-408 - UGCUCUCCCCAAUCCACUCC 20 4257

SCNNlA-8 - AGCCCUCCACAGUCCACUCC 20 559

SCNNlA-45 + UGAAGUACUCUCCGAAAAGC 20 579

SCNNlA-5 - UCUCAUGGAGGGGAACAAGC 20 557

SCNNlA-409 + CUCCCCUUGGAAGGGACAGC 20 4258

SCNNlA-17 - CAAGCGUGAGGAGCAGGGGC 20 563

SCNNlA-38 + AGGGUGCAGAUGGUCACUGC 20 575

SCNNlA-65 + CCUCCUCCGCCGUGGGCUGC 20 594

SCNNlA-49 + CCGUCUUCAUGCGGUUGUGC 20 582

SCNNlA-61 + AGGAGCGGUGGAACUCGAUC 20 591

SCNNlA-410 - UUGCUCUCCCCAAUCCACUC 20 4259

SCNNlA-411 + UCAGGGUCAAGGCUGAGCUC 20 4260

SCNNlA-28 - ACCGCAUGAAGACGGCCUUC 20 570

SCNNlA-70 + UGCUGGGGCGCCGCAGGUUC 20 598

SCNNlA-412 - AUCCAGCUGUCCCUUCCAAG 20 4261

SCNNlA-413 - UGGGACAUGGGCAUGGCCAG 20 4262

SCNNlA-414 - CAGCCUCACUCGGGUUCCAG 20 4263

SCNNlA-415 + AGACCUGGUAUGGGCUGCAG 20 4264

SCNNlA-59 + CGAAGAGCUCUCGGUAGGAG 20 589

SCNNlA-4 - CCAUACCAGGUCUCAUGGAG 20 498

SCNNlA-63 + CAGGGCCUCCUCCUCCGCCG 20 592

SCNNlA-52 + UGUGCUGGGAGCACACCAGG 20 584

1193

5535.1 SCNNlA-23 - CCAGCAGCCCACGGCGGAGG 20 566

SCNNlA-60 + AGAGCUCUCGGUAGGAGCGG 20 590

SCNNlA-416 - CAGCUGUCCCUUCCAAGGGG 20 4265

SCNNlA-75 + AGCCCUGGAGUGGACUGUGG 20 602

SCNNlA-48 + CCCAGAAGGCCGUCUUCAUG 20 581

SCNNlA-74 + AUGAGCCCUGGAGUGGACUG 20 601

SCNNlA-67 + UCCUCCGCCGUGGGCUGCUG 20 596

SCNNlA-417 + UCACCCCUGGAACCCGAGUG 20 4266

SCNNlA-13 - CA U G AAG GG G AAC AAG CG U G 20 562

SCNNlA-418 + UAACCGACCUGUAGGGAUUG 20 4267

SCNNlA-419 + AUGAGCCCCGGAGUGGAUUG 20 4268

SCNNlA-40 + AGACGAGCUUGUCCGAGUUG 20 576

SCNNlA-41 + CCGAGUUGAGGUUGAUGUUG 20 577

SCNNlA-420 + UCAUGAGCCCCGGAGUGGAU 20 4269

SCNNlA-421 - ACUCGGGUUCCAGGGGUGAU 20 4270

SCNNlA-79 + CCCUCCAUGAGACCUGGUAU 20 604

SCNNlA-35 - CCUCAACAUCAACCUCAACU 20 574

SCNNlA-18 - AAGCGUGAGGAGCAGGGGCU 20 564

SCNNlA-66 + CUCCUCCGCCGUGGGCUGCU 20 595

SCNNlA-50 + CGUCUUCAUGCGGUUGUGCU 20 583

SCNNlA-57 + AGAAGAACUCGAAGAGCUCU 20 588

SCNNlA-422 + CAGGGUCAAGGCUGAGCUCU 20 4271

SCNNlA-29 - CCGCAUGAAGACGGCCUUCU 20 571

SCNNlA-64 + AGGGCCUCCUCCUCCGCCGU 20 593

SCNNlA-423 - CACCCUCAAUCCCUACAGGU 20 4272

SCNNlA-424 + AGAGGGACUAACCGACCUGU 20 4273

SCNNlA-425 + CAUGAGCCCCGGAGUGGAUU 20 4274

SCNNlA-69 + CUGCUGGGGCGCCGCAGGUU 20 597

SCNNlA-34 - UGGCAAUUCGGCCUGCUUUU 20 573

Table 43C provides exemplary targeting domains for knocking out the SCNN1A gene selected according to the third tier parameters. The targeting domains bind within the first 500 bp of the coding sequence (e.g., with 500 bp downstream from the start codon) and start with a 5'G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. pyogeness Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 43C

3rd Tier

1194

5535.1 Target Site gRNA Name DNA Strand Targeting Domain

Length Seq ID

SCNNlA-426 - GGACAUGGGCAUGGCCA 17 4275

SCNNlA-427 + GUGGAUUGGGGAGAGCA 17 4276

SCNNlA-428 + GGGGAGAGCAAGGGUCA 17 4277

SCNNlA-115 + GGGAUUGAGGGUGCAGA 17 542

SCNNlA-134 + GCGGAUGGCGCCGUGGA 17 548

SCNNlA-429 - GGGACAUGGGCAUGGCC 17 4278

SCNNlA-86 - GAACAAGCUGGAGGAGC 17 531

SCNNlA-96 - GCGUGAGGAGCAGGGGC 17 534

SCNNlA-430 + GGGUCAAGGCUGAGCUC 17 4279

SCNNlA-100 - GCCCCAGCAGCCCACGG 17 537

SCNNlA-135 + GAUGGCGCCGUGGAUGG 17 549

SCNNlA-431 - GAAGGGGAACAAGCUGG 17 4280

SCNNlA-85 - GGAGGGGAACAAGCUGG 17 530

SCNNlA-92 - GAAGGGGAACAAGCGUG 17 532

SCNNlA-432 + GAGUGGAUUGGGGAGAGCAA 20 4281

SCNNlA-9 - GCCCUCCACAGUCCACUCCA 20 499

SCNNlA-433 + GGAGUGGAUUGGGGAGAGCA 20 4282

SCNNlA-434 + GAGAGCAAGGGUCAGGGUCA 20 4283

SCNNlA-47 + GAGCCACAGCACUGCCCAGA 20 521

SCNNlA-435 - GUUCCAGGGGUGAUGGGAGA 20 4284

SCNNlA-7 - GGGGAACAAGCUGGAGGAGC 20 504

SCNNlA-14 - GGGGAACAAGCGUGAGGAGC 20 506

SCNNlA-436 - GGUUCCAGGGGUGAUGGGAG 20 4285

SCNNlA-24 - GCAGCCCACGGCGGAGGAGG 20 512

SCNNlA-56 + GCGGAUGGCGCCGUGGAUGG 20 523

SCNNlA-437 - GUAAGCAAGGGAACCUGGUU 20 4286

Table 43D provides exemplary targeting domains for knocking out the SCNN1A gene selected according to the fourth tier parameters. The targeting domains bind within the first 500 bp of the coding sequence (e.g., with 500 bp downstream from the start codon). It is

contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. pyogeness Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 43D

1195

5535.1 Length

SCNNlA-438 + UGGAUUGGGGAGAGCAA 17 4287

SCNNlA-439 - UCCAGCUGUCCCUUCCA 17 4288

SCNNlA-440 - AGGGUGGGACAUGGGCA 17 4289

SCNNlA-441 + AGCAAGGGUCAGGGUCA 17 4290

SCNNlA-442 + ACCAGGGAAGGGGCAGA 17 4291

SCNNlA-443 - CCAGGGGUGAUGGGAGA 17 4292

SCNNlA-155 + CUGGAGUGGACUGUGGA 17 652

SCNNlA-444 + UGGGCUGCAGAGGUCUA 17 4293

SCNNlA-445 - AGGUAAGCAAGGGAACC 17 4294

SCNNlA-446 + CCCUCUCCCAUCACCCC 17 4295

SCNNlA-151 + UUCCCCUUCAUGAGCCC 17 648

SCNNlA-447 - UCCCUCUGCCCCUUCCC 17 4296

SCNNlA-105 - CCACGGCGCCAUCCGCC 17 618

SCNNlA-448 - UCCAGGGGUGAUGGGAG 17 4297

SCNNlA-83 - UACCAGGUCUCAUGGAG 17 606

SCNNlA-133 + CCAGGCGGAUGGCGCCG 17 638

SCNNlA-154 + CCUGGAGUGGACUGUGG 17 651

SCNNlA-153 + AGCCCUGGAGUGGACUG 17 650

SCNNlA-109 - CCUUCUGGGCAGUGCUG 17 620

SCNNlA-449 - CCAGGGGCAGCCUCACU 17 4298

SCNNlA-450 + CUCAUGAUACCUCCCCU 17 4299

SCNNlA-11 - UCCACUCCAGGGCUCAUGAA 20 560

SCNNlA-451 - UCCACUCCGGGGCUCAUGAA 20 4300

SCNNlA-452 - CGCAGGGUGGGACAUGGGCA 20 4301

SCNNlA-55 + CAGGCGGAUGGCGCCGUGGA 20 587

SCNNlA-77 + UUGUUCCCCUCCAUGAGACC 20 603

SCNNlA-72 + UUGUUCCCCUUCAUGAGCCC 20 599

SCNNlA-26 - CAUCCACGGCGCCAUCCGCC 20 568

SCNNlA-12 - CCACUCCAGGGCUCAUGAAG 20 561

SCNNlA-453 - CCACUCCGGGGCUCAUGAAG 20 4302

SCNNlA-454 + CCCCUUCAUGAGCCCCGGAG 20 4303

SCNNlA-73 + CCCCUUCAUGAGCCCUGGAG 20 600

SCNNlA-54 + ACACCAGGCGGAUGGCGCCG 20 586

SCNNlA-455 - CAUGAAGGGGAACAAGCUGG 20 4304

SCNNlA-6 - CAUGGAGGGGAACAAGCUGG 20 558

SCNNlA-30 - CGGCCUUCUGGGCAGUGCUG 20 572

SCNNlA-456 - UGGCCAGGGGCAGCCUCACU 20 4305

SCNNlA-457 + CUGCUCAUGAUACCUCCCCU 20 4306

Table 43E provides exemplary targeting domains for knocking out the SCNNIA gene selected according to the fifth tier parameters. The targeting domains fall in the coding sequence

1196

5535.1 of the gene, downstream of the first 500bp of coding sequence (e.g., anywhere from +500 (relative to the start codon) to the stop codon of the gene). It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. pyogeness Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 43E

1197

5535.1 SCNNlA-489 + GUUGUUGAUUCCAGGCA 17 4338

SCNNlA-490 + CCAGGGUGGCAUAGGCA 17 4339

SCNNlA-491 - UCCAGGCCGAGGGGGCA 17 4340

SCNNlA-492 + GGGGACACUAACCUGCA 17 4341

SCNNlA-493 + GACCCUCAGGCGCUGCA 17 4342

SCNNlA-494 - CUCCAGGGGGCUCUGCA 17 4343

SCNNlA-495 - GCCCGGGUAAUGGUGCA 17 4344

SCNNlA-496 + CUCUGCGCGCAGCAUCA 17 4345

SCNNlA-497 - ACCAGACAUACUCAUCA 17 4346

SCNNlA-498 + GAAUGGGGGUGUCAUCA 17 4347

SCNNlA-499 - CCAGGAGAGCAUGAUCA 17 4348

SCNNlA-500 - GUCCCGCCCCCGCCUCA 17 4349

SCNNlA-501 + CCUCUCCUUCCCUCUCA 17 4350

SCNNlA-502 + AGGGGGAGGGGCUGUCA 17 4351

SCNNlA-503 - UGAGUCUCCCUCUGUCA 17 4352

SCNNlA-504 - AGUCAACAUCUUCUUCA 17 4353

SCNNlA-505 + AAGGGGCGAGGGGAAGA 17 4354

SCNNlA-506 - ACCUCUCCUCUCACAGA 17 4355

SCNNlA-507 + CGACCUACCGUGACAGA 17 4356

SCNNlA-508 + CUUAGGUGUGGGGCAGA 17 4357

SCNNlA-509 + CAGAGACUAGAGUCAGA 17 4358

SCNNlA-510 + GGAGGGUGGAGAGGAGA 17 4359

SCNNlA-511 + GCAGAGCCCCCUGGAGA 17 4360

SCNNlA-512 + GCUGUCAAGGCUGGAGA 17 4361

SCNNlA-513 - GUUGUCUGUGGUGGAGA 17 4362

SCNNlA-514 - CUGGGGGGGCCCUGAGA 17 4363

SCNNlA-515 - CUGCUGGUUACUCACGA 17 4364

SCNNlA-516 + GAGAGGUACAUUGACGA 17 4365

SCNNlA-517 + ACCUGGGAUGUCACCGA 17 4366

SCNNlA-518 - GAGGCCCGCAGCGCCGA 17 4367

SCNNlA-519 - ACUGGUCUCCAGGCCGA 17 4368

SCNNlA-520 - UCCUCAUGCUGCUCCGA 17 4369

SCNNlA-521 + UCCCCCGCAGGUCGCGA 17 4370

SCNNlA-522 + GGUACCUGAAGGGGCGA 17 4371

SCNNlA-523 + CCACGCUACGGGCUCGA 17 4372

SCNNlA-524 + GGCAGAAGUGGGAAGGA 17 4373

SCNNlA-525 + GCCCAGGUUGGACAGGA 17 4374

SCNNlA-526 + ACACCUGGAAGGGAGGA 17 4375

SCNNlA-527 - CUCCAUCAGCAUGAGGA 17 4376

SCNNlA-528 - AGAGUGUGGGGAAGGGA 17 4377

SCNNlA-529 + GUGUCCUCCUCCAGGGA 17 4378

SCNNlA-530 - GGGGGCCCUGAGAGGGA 17 4379

1198

5535.1 SCNNlA-531 + CAACCUGUACCCGGGGA 17 4380

SCNNlA-532 + UGGCAUAGGCAGGGGGA 17 4381

SCNNlA-533 + GCUGGUCACGCUGGGGA 17 4382

SCNNlA-534 - CAGGUAGAGUGUGGGGA 17 4383

SCNNlA-535 + UGGGGGCAGAAGUGGGA 17 4384

SCNNlA-536 - CCCCCAGGUGGACUGGA 17 4385

SCNNlA-537 + GUGAAUACACACCUGGA 17 4386

SCNNlA-538 - UGACUGGGAGGCCUGGA 17 4387

SCNNlA-539 - GGUAGGUCGUGCCUGGA 17 4388

SCNNlA-540 - CCUGCCUUUAUGGAUGA 17 4389

SCNNlA-541 + AAUUUCCGGGUACCUGA 17 4390

SCNNlA-542 - CCCCUUGCAGCGCCUGA 17 4391

SCNNlA-543 + UGCCUUCCUCAUGCUGA 17 4392

SCNNlA-544 - AGGGGUGGAUGCGGUGA 17 4393

SCNNlA-545 + GGCCACGAGAGUGGUGA 17 4394

SCNNlA-546 + UGACCUCUUGUUGUUGA 17 4395

SCNNlA-547 + UGCUGUGUGUACUUUGA 17 4396

SCNNlA-548 - CUCUCUCUUUCCUGAUA 17 4397

SCNNlA-549 + CAUCAGGGACAGACCUA 17 4398

SCNNlA-550 + AGCUGGAGGCCACGCUA 17 4399

SCNNlA-551 + UCAGGAAAGAGAGAGUA 17 4400

SCNNlA-552 - UUCCACCACCCGAUGUA 17 4401

SCNNlA-553 - AGACUUGGGGGCGAUUA 17 4402

SCNNlA-554 - GGAUGAACCUGCCUUUA 17 4403

SCNNlA-555 + GGGUAAAGGUUCUCAAC 17 4404

SCNNlA-556 + AGGACAGGUGGAGGAAC 17 4405

SCNNlA-557 + CCGAGGAGCCGAACCAC 17 4406

SCNNlA-558 - CAUCUCUCUGUACCCAC 17 4407

SCNNlA-559 + CGAACCACAGGCUCCAC 17 4408

SCNNlA-560 - CCCGGGUAAUGGUGCAC 17 4409

SCNNlA-561 + AUUUGUUCUGGUUGCAC 17 4410

SCNNlA-562 - UCCCGCCCCCGCCUCAC 17 4411

SCNNlA-563 + UCUCUGGCAGCCUCGAC 17 4412

SCNNlA-564 + CACGCUACGGGCUCGAC 17 4413

SCNNlA-565 - AGGUGGACUGGAAGGAC 17 4414

SCNNlA-566 + GGGCCCCCCCAGAGGAC 17 4415

SCNNlA-567 - ACAACCCCCAGGUGGAC 17 4416

SCNNlA-568 + GGCUGCCCAGGUUGGAC 17 4417

SCNNlA-569 - AAGGCAAGGAUGCUGAC 17 4418

SCNNlA-570 - CUGCUGUCCACAGUGAC 17 4419

SCNNlA-571 - GGUUCCGAAGCCGAUAC 17 4420

SCNNlA-572 + GCUGGAGGCCACGCUAC 17 4421

1199

5535.1 SCNNlA-573 - UCCCCUUCCCCGGGUAC 17 4422

SCNNlA-574 + AGGAGCUGUAUUUGUAC 17 4423

SCNNlA-575 - CACCCUCCUGUCCAACC 17 4424

SCNNlA-576 - CCAGGUCUCCUGCAACC 17 4425

SCNNlA-577 + CUGAGGAGAAGUCAACC 17 4426

SCNNlA-578 - CGCCUGCCGCUUCAACC 17 4427

SCNNlA-579 + AGGAGUGAAUACACACC 17 4428

SCNNlA-580 - CUUCUCCUCAGACCACC 17 4429

SCNNlA-581 + AGUCCUUCCAGUCCACC 17 4430

SCNNlA-582 + CCUGGUUGCAGGAGACC 17 4431

SCNNlA-583 + CUUCCCCACACUCUACC 17 4432

SCNNlA-584 - UCGCCCCUUCAGGUACC 17 4433

SCNNlA-585 + GCCCGUGCACCAUUACC 17 4434

SCNNlA-586 - GGGUUCAUAGGAAACCC 17 4435

SCNNlA-587 - CCCUGCCUAUGCCACCC 17 4436

SCNNlA-588 - GGAGGUAGCCUCCACCC 17 4437

SCNNlA-589 + CCCGUGCACCAUUACCC 17 4438

SCNNlA-590 + CCCUGGAGUCUCACCCC 17 4439

SCNNlA-591 - GCGGGACAACAACCCCC 17 4440

SCNNlA-592 + GCCCCUGCAGAGCCCCC 17 4441

SCNNlA-593 - UUAGUGUCCCCUUCCCC 17 4442

SCNNlA-594 + ACUUGGUGAAACAGCCC 17 4443

SCNNlA-595 + GAGAUGGGCGGGGGCCC 17 4444

SCNNlA-596 - CACAGUGACUGGGGCCC 17 4445

SCNNlA-597 - AGAGGUCAGUCCUGCCC 17 4446

SCNNlA-598 + GGCUCCACUGGCUGCCC 17 4447

SCNNlA-599 - GCCCUCGGUGACAUCCC 17 4448

SCNNlA-600 - AGAGACUCUGCCAUCCC 17 4449

SCNNlA-601 + GCAGGGUGGGGGCUCCC 17 4450

SCNNlA-602 - GUUAGUGUCCCCUUCCC 17 4451

SCNNlA-603 - CUGUCCUUGUCCCAGCC 17 4452

SCNNlA-604 + AUGGAGGUCUCCACGCC 17 4453

SCNNlA-605 + CAGGACUGACUCACGCC 17 4454

SCNNlA-606 - AUGCUGACUGGGAGGCC 17 4455

SCNNlA-607 - GGCUUUAACUUGCGGCC 17 4456

SCNNlA-608 + CCCCUGCCCCCUCGGCC 17 4457

SCNNlA-609 + GGAGAGGGAGCAGGGCC 17 4458

SCNNlA-610 - CCACAGUGACUGGGGCC 17 4459

SCNNlA-611 - UGGAUGUCUUCCAUGCC 17 4460

SCNNlA-612 + AAGGAGGGGAGGAUGCC 17 4461

SCNNlA-613 - CGUGAGUCAGUCCUGCC 17 4462

SCNNlA-614 - UCACGGUAGGUCGUGCC 17 4463

1200

5535.1 SCNNlA-615 + CAUCACAGGCUCCAUCC 17 4464

SCNNlA-616 - UCCUGGGGUGAGACUCC 17 4465

SCNNlA-617 + CCAGCGUGUCCUCCUCC 17 4466

SCNNlA-618 - CUGCUACUAUAAGCUCC 17 4467

SCNNlA-619 - GGCCCCCGCCCAUCUCC 17 4468

SCNNlA-620 + CCUUGAUCAUGCUCUCC 17 4469

SCNNlA-621 - AGCCGAUACUGGUCUCC 17 4470

SCNNlA-622 + CGCCCCCAAGUCUGUCC 17 4471

SCNNlA-623 + UCACCGUUGUUGAUUCC 17 4472

SCNNlA-624 - CCACCCUCCUCCCUUCC 17 4473

SCNNlA-625 - UAUUCACUCCUGCUUCC 17 4474

SCNNlA-626 - ACAGAAAG CACAG U U CC 17 4475

SCNNlA-627 + GCUCCUCUUUAAUUUCC 17 4476

SCNNlA-628 + GGCGCCAUGGAGCAAGC 17 4477

SCNNlA-629 + GUUGUUGUCCCGCAAGC 17 4478

SCNNlA-630 + CAUGCUCUCCUGGAAGC 17 4479

SCNNlA-631 - U U C AAAG U AC ACAC AG C 17 4480

SCNNlA-632 + CAGUCACUGUGGACAGC 17 4481

SCNNlA-633 + CUGCGGGCCUCACCAGC 17 4482

SCNNlA-634 + GGAACAUGAUGACCAGC 17 4483

SCNNlA-635 - GAAGAUCGGCUUCCAGC 17 4484

SCNNlA-636 + AGUAACCAGCAGAGAGC 17 4485

SCNNlA-637 - GGAAAUUAAAGAGGAGC 17 4486

SCNNlA-638 - AGAGGAGCUGGAGGAGC 17 4487

SCNNlA-639 + AAGGCUGGAGAGGGAGC 17 4488

SCNNlA-640 + GCGACGGCUGCGGGAGC 17 4489

SCNNlA-641 + AGCAGAGAGCUGGUAGC 17 4490

SCNNlA-642 - CCUGGAGGAGGACACGC 17 4491

SCNNlA-643 + CUGGUAGCUGGUCACGC 17 4492

SCNNlA-644 + GCGGCAGAGUCCCCCGC 17 4493

SCNNlA-645 + CCAUCAUCCAUAAAGGC 17 4494

SCNNlA-646 + GGAGGGGCUGUCAAGGC 17 4495

SCNNlA-647 + AGAGCAAGGAGCCAGGC 17 4496

SCNNlA-648 + GACGGGCCCCGUGAGGC 17 4497

SCNNlA-649 + CCCAGGGUGGCAUAGGC 17 4498

SCNNlA-650 + GACCUGGUUGAAGCGGC 17 4499

SCNNlA-651 + GUGGCUGGGACCAGGGC 17 4500

SCNNlA-652 - GGUAAUGGUGCACGGGC 17 4501

SCNNlA-653 - CUCCAGGCCGAGGGGGC 17 4502

SCNNlA-654 + CCCCGUGAGGCGGGGGC 17 4503

SCNNlA-655 + GCCCCCUGGAGAUGGGC 17 4504

SCNNlA-656 + AGGGAGCAGGGCCUGGC 17 4505

1201

5535.1 SCNNlA-657 - UUCACCACUCUCGUGGC 17 4506

SCNNlA-658 - AGUGCCGGAAGCCAUGC 17 4507

SCNNlA-659 - CAGCCGUCGCGACCUGC 17 4508

SCNNlA-660 - GCUCGUCUUUGACCUGC 17 4509

SCNNlA-661 + GGGCCCCUCGGCGCUGC 17 4510

SCNNlA-662 + CAGGUCGCGACGGCUGC 17 4511

SCNNlA-663 - UCUCCAGGGGGCUCUGC 17 4512

SCNNlA-664 - AGCUACCAGCUCUCUGC 17 4513

SCNNlA-665 - GCUGUUUCACCAAGUGC 17 4514

SCNNlA-666 - CGUGGCCUCCAGCUUGC 17 4515

SCNNlA-667 + GACUCACGCCUGGUUGC 17 4516

SCNNlA-668 + AGCAGUUUCCAUACAUC 17 4517

SCNNlA-669 + GCUCUGCGCGCAGCAUC 17 4518

SCNNlA-670 + UCUGUCGCGAUAGCAUC 17 4519

SCNNlA-671 - UACCAGACAUACUCAUC 17 4520

SCNNlA-672 + GAGAGUAAUUCCUUAUC 17 4521

SCNNlA-673 - AGAACAACUCCAACCUC 17 4522

SCNNlA-674 + GCGGGGGCGGGACCCUC 17 4523

SCNNlA-675 - UUCCUCCACCUGUCCUC 17 4524

SCNNlA-676 - AGGGGGCAGGGGUGCUC 17 4525

SCNNlA-677 + ACCUCUCCUUCCCUCUC 17 4526

SCNNlA-678 + AGGGAUGGCAGAGUCUC 17 4527

SCNNlA-679 + GCGAGGGGAAGAGGGUC 17 4528

SCNNlA-680 + CCCCUGAUGAGUAUGUC 17 4529

SCNNlA-681 - CUUCCCCUCGCCCCUUC 17 4530

SCNNlA-682 + CUAACCUGCAUGGCUUC 17 4531

SCNNlA-683 + CACAGUACUCCACGUUC 17 4532

SCNNlA-684 + AGCAGUCCGAUUUGUUC 17 4533

SCNNlA-685 + AGCUCCUCUUUAAUUUC 17 4534

SCNNlA-686 - G U ACCCGG AAAU UAAAG 17 4535

SCNNlA-687 - AC ACCG U C AACAAC AAG 17 4536

SCNNlA-688 + CCCUCAGGCGCUGCAAG 17 4537

SCNNlA-689 + UGGGGUGGGGGCAGAAG 17 4538

SCNNlA-690 + GAAGGGGCGAGGGGAAG 17 4539

SCNNlA-691 + ACCUGUACCCGGGGAAG 17 4540

SCNNlA-692 + UGUUGAUGUAGUGGAAG 17 4541

SCNNlA-693 + UUUCCGGGUACCUGAAG 17 4542

SCNNlA-694 + AGGAGACCUGGUUGAAG 17 4543

SCNNlA-695 + ACGACCUACCGUGACAG 17 4544

SCNNlA-696 + UCUCAGGGCCCCCCCAG 17 4545

SCNNlA-697 - CCAACCUGGGCAGCCAG 17 4546

SCNNlA-698 + GCAUGGAAGACAUCCAG 17 4547

1202

5535.1 SCNNlA-699 - CCCCCGCCCAUCUCCAG 17 4548

SCNNlA-700 + GUCACUGUGGACAGCAG 17 4549

SCNNlA-701 + CAGGGUGGCAUAGGCAG 17 4550

SCNNlA-702 - CCAGGCCGAGGGGGCAG 17 4551

SCNNlA-703 + UCUUAGGUGUGGGGCAG 17 4552

SCNNlA-704 - UCCAGGGGGCUCUGCAG 17 4553

SCNNlA-705 - CCAGACAUACUCAUCAG 17 4554

SCNNlA-706 + ACAGAGACUAGAGUCAG 17 4555

SCNNlA-707 + AGAGACUAGAGUCAGAG 17 4556

SCNNlA-708 + GGAGCCGGCCACGAGAG 17 4557

SCNNlA-709 - AGGCCCGCAGCGCCGAG 17 4558

SCNNlA-710 - CUGGUCUCCAGGCCGAG 17 4559

SCNNlA-711 + GUACCUGAAGGGGCGAG 17 4560

SCNNlA-712 - CCCUGAGAGGGAAGGAG 17 4561

SCNNlA-713 + GCAGAAGUGGGAAGGAG 17 4562

SCNNlA-714 + AGGAGGGUGGAGAGGAG 17 4563

SCNNlA-715 + ACCAUCUGUGAGAGGAG 17 4564

SCNNlA-716 - UGGAUGCGGUGAGGGAG 17 4565

SCNNlA-717 + GGCAUAGGCAGGGGGAG 17 4566

SCNNlA-718 - ACACCUAAGAAAUGGAG 17 4567

SCNNlA-719 + GGCUGUCAAGGCUGGAG 17 4568

SCNNlA-720 + AAGGGAGGAGGGUGGAG 17 4569

SCNNlA-721 - UCUGGGGGGGCCCUGAG 17 4570

SCNNlA-722 + GGGUGACCAUCUGUGAG 17 4571

SCNNlA-723 + AUCAGGGACAGACCUAG 17 4572

SCNNlA-724 + ACAGGAUGUUGAUGUAG 17 4573

SCNNlA-725 - UCCGCGGCCCCAGAACG 17 4574

SCNNlA-726 - CCCGCCCCCGCCUCACG 17 4575

SCNNlA-727 + CACCACAGACAACACCG 17 4576

SCNNlA-728 + UACCUGGGAUGUCACCG 17 4577

SCNNlA-729 - UGAGGCCCGCAGCGCCG 17 4578

SCNNlA-730 - UACUGGUCUCCAGGCCG 17 4579

SCNNlA-731 + UCCACGUUCUGGGGCCG 17 4580

SCNNlA-732 - CCUACAUCUUCUAUCCG 17 4581

SCNNlA-733 - GGCCCAACCUGAUUCCG 17 4582

SCNNlA-734 - CCGUCGAGCCCGUAGCG 17 4583

SCNNlA-735 + ACGGGCCCCGUGAGGCG 17 4584

SCNNlA-736 + GGGUACCUGAAGGGGCG 17 4585

SCNNlA-737 + CCCCCUGGAGAUGGGCG 17 4586

SCNNlA-738 - UAACUUGCGGCCUGGCG 17 4587

SCNNlA-739 - AGCCGUCGCGACCUGCG 17 4588

SCNNlA-740 - CUCCUUCACCACUCUCG 17 4589

1203

5535.1 SCNNlA-741 - ACAUCAACAUCCUGUCG 17 4590

SCNNlA-742 + GGGCAGAAGUGGGAAGG 17 4591

SCNNlA-743 + CCCCCCCAGAGGACAGG 17 4592

SCNNlA-744 + UGCCCAGGUUGGACAGG 17 4593

SCNNlA-745 - GGACAACAACCCCCAGG 17 4594

SCNNlA-746 + UGGUGAAACAGCCCAGG 17 4595

SCNNlA-747 - CCCCGCCCAUCUCCAGG 17 4596

SCNNlA-748 + AGGGUGGCAUAGGCAGG 17 4597

SCNNlA-749 - GGGCAGGGGUGCUCAGG 17 4598

SCNNlA-750 - UGGUCUCCAGGCCGAGG 17 4599

SCNNlA-751 + CACACCUGGAAGGGAGG 17 4600

SCNNlA-752 - UCUGCCAUCCCUGGAGG 17 4601

SCNNlA-753 + CGACGGGCCCCGUGAGG 17 4602

SCNNlA-754 + CGGGCCCCGUGAGGCGG 17 4603

SCNNlA-755 + CCCCUGGAGAUGGGCGG 17 4604

SCNNlA-756 - GCCGUCGCGACCUGCGG 17 4605

SCNNlA-757 + AUACACACCUGGAAGGG 17 4606

SCNNlA-758 + UGGGCGGGGGCCCAGGG 17 4607

SCNNlA-759 + AGGGGAGGAUGCCAGGG 17 4608

SCNNlA-760 + AGGUGUGGGGCAGAGGG 17 4609

SCNNlA-761 + CCUGGAAGGGAGGAGGG 17 4610

SCNNlA-762 + AGUUUCCAUACAUCGGG 17 4611

SCNNlA-763 - GACAUACUCAUCAGGGG 17 4612

SCNNlA-764 + GAAGUGGGAAGGAGGGG 17 4613

SCNNlA-765 + GUGGCAUAGGCAGGGGG 17 4614

SCNNlA-766 + GCCCCGUGAGGCGGGGG 17 4615

SCNNlA-767 + AGGACAGAGACAUGGGG 17 4616

SCNNlA-768 - CCACCUGUCCUCUGGGG 17 4617

SCNNlA-769 + AGCCCCCUGGAGAUGGG 17 4618

SCNNlA-770 - UGUGGGGAAGGGAUGGG 17 4619

SCNNlA-771 - CAAGGAUGCUGACUGGG 17 4620

SCNNlA-772 - UCCACCUGUCCUCUGGG 17 4621

SCNNlA-773 + UUCCUAGGAAAGAAUGG 17 4622

SCNNlA-774 - GCCUUUAUGGAUGAUGG 17 4623

SCNNlA-775 + CUUCCUCAUGCUGAUGG 17 4624

SCNNlA-776 + CCUUCCAGUCCACCUGG 17 4625

SCNNlA-777 - GACUCUGCCAUCCCUGG 17 4626

SCNNlA-778 + GUUGUCCCGCAAGCUGG 17 4627

SCNNlA-779 - AAUUAAAGAGGAGCUGG 17 4628

SCNNlA-780 - CUCCACCUGUCCUCUGG 17 4629

SCNNlA-781 + CCCCAGAGGACAGGUGG 17 4630

SCNNlA-782 + GGAGGAUGCCAGGGUGG 17 4631

1204

5535.1 SCNNlA-783 + UUCCAUACAUCGGGUGG 17 4632

SCNNlA-784 + ACAGAGACAUGGGGUGG 17 4633

SCNNlA-785 - GGGGAAGGGAUGGGUGG 17 4634

SCNNlA-786 - CUCGGUGUUGUCUGUGG 17 4635

SCNNlA-787 - ACCCUGGACAGACUUGG 17 4636

SCNNlA-788 + AUUCCUAGGAAAGAAUG 17 4637

SCNNlA-789 + ACAAGGACAGAGACAUG 17 4638

SCNNlA-790 + ACCUUCGGAGCAGCAUG 17 4639

SCNNlA-791 - AGACCUCCAUCAGCAUG 17 4640

SCNNlA-792 - CUCAUCAGGGGUGGAUG 17 4641

SCNNlA-793 + GCGUCUGCUCUGUGAUG 17 4642

SCNNlA-794 - UGAUCUCUUGGUGUAUG 17 4643

SCNNlA-795 + CCGGGCCCCAGUCACUG 17 4644

SCNNlA-796 - GCUGUCCACAGUGACUG 17 4645

SCNNlA-797 + UCCUUCCAGUCCACCUG 17 4646

SCNNlA-798 - GCAGCCGUCGCGACCUG 17 4647

SCNNlA-799 + AUAGUAGCAGUACCCUG 17 4648

SCNNlA-800 - GCAGCCAGUGGAGCCUG 17 4649

SCNNlA-801 - ACCCCUUGCAGCGCCUG 17 4650

SCNNlA-802 - AG AAAG C ACAG U U CC U G 17 4651

SCNNlA-803 + GGUAGCUGGUCACGCUG 17 4652

SCNNlA-804 + CGGGCCCCUCGGCGCUG 17 4653

SCNNlA-805 + GCAGGUCGCGACGGCUG 17 4654

SCNNlA-806 - CCUCCACCUGUCCUCUG 17 4655

SCNNlA-807 + ACAGCCCAGGUGGUCUG 17 4656

SCNNlA-808 - CUCCUCGGUGUUGUCUG 17 4657

SCNNlA-809 + CAGUACUCCACGUUCUG 17 4658

SCNNlA-810 - ACAU CCCAGG U AG AG UG 17 4659

SCNNlA-811 - AGCAUGAUCAAGGAGUG 17 4660

SCNNlA-812 + GCUCGACGGGCCCCGUG 17 4661

SCNNlA-813 - AGUACACACAGCAGGUG 17 4662

SCNNlA-814 + ACUCCAUUUCUUAGGUG 17 4663

SCNNlA-815 - CAGGGGUGGAUGCGGUG 17 4664

SCNNlA-816 + AGGCGCUGCAAGGGGUG 17 4665

SCNNlA-817 + GACAGAGACAUGGGGUG 17 4666

SCNNlA-818 - UGGGGAAGGGAUGGGUG 17 4667

SCNNlA-819 - UCGGCUUCCAGCUGGUG 17 4668

SCNNlA-820 - AUCCCAGGUAGAGUGUG 17 4669

SCNNlA-821 + UCCAUUUCUUAGGUGUG 17 4670

SCNNlA-822 - AUGGUGGCUUUAACUUG 17 4671

SCNNlA-823 - AACCCUGGACAGACUUG 17 4672

SCNNlA-824 - GCGUGGCCUCCAGCUUG 17 4673

1205

5535.1 SCNNlA-825 - G U G C AACC AG AAC AAAU 17 4674

SCNNlA-826 + CAUUCCUAGGAAAGAAU 17 4675

SCNNlA-827 + AGAGGGAGACUCAGAAU 17 4676

SCNNlA-828 - CAUUCUUUCCUAGGAAU 17 4677

SCNNlA-829 + GACAAGGACAGAGACAU 17 4678

SCNNlA-830 + UAGCAGUUUCCAUACAU 17 4679

SCNNlA-831 + GGGGCCCAGGGUGGCAU 17 4680

SCNNlA-832 - GGUGUAUGUGGGUUCAU 17 4681

SCNNlA-833 - UGGAAGGACUGGAAGAU 17 4682

SCNNlA-834 + CAGAGCCCCCUGGAGAU 17 4683

SCNNlA-835 + AGAGGUACAUUGACGAU 17 4684

SCNNlA-836 - GAGUGUGGGGAAGGGAU 17 4685

SCNNlA-837 + GGCCUGGAGACCAGUAU 17 4686

SCNNlA-838 + GCAUGGCUUCCGGCACU 17 4687

SCNNlA-839 - GAAACCCUGGACAGACU 17 4688

SCNNlA-840 - AGGCAAGGAUGCUGACU 17 4689

SCNNlA-841 - UGCUGUCCACAGUGACU 17 4690

SCNNlA-842 - ACCCUCCUGUCCAACCU 17 4691

SCNNlA-843 - UUCUCCUCAGACCACCU 17 4692

SCNNlA-844 + GUCCUUCCAGUCCACCU 17 4693

SCNNlA-845 + GCAUCAGGGACAGACCU 17 4694

SCNNlA-846 + UUCCCCACACUCUACCU 17 4695

SCNNlA-847 - CCUGCCUAUGCCACCCU 17 4696

SCNNlA-848 - GCUCUCUCUGCACCCCU 17 4697

SCNNlA-849 + GAGCACCCCUGCCCCCU 17 4698

SCNNlA-850 - UUACUCACGAUGGCCCU 17 4699

SCNNlA-851 - CCUGUGGUUCGGCUCCU 17 4700

SCNNlA-852 + CUGGAAGACCCAUUCCU 17 4701

SCNNlA-853 - C AG A A AG C ACAG U U CC U 17 4702

SCNNlA-854 - CACCCCCAUUCUUUCCU 17 4703

SCNNlA-855 - CUGGAGGAGGACACGCU 17 4704

SCNNlA-856 + UGGUAGCUGGUCACGCU 17 4705

SCNNlA-857 + GGGAGCAGGGCCUGGCU 17 4706

SCNNlA-858 - UCCUCCACCUGUCCUCU 17 4707

SCNNlA-859 + AACAUCACUGCCAUUCU 17 4708

SCNNlA-860 + ACAGUACUCCACGUUCU 17 4709

SCNNlA-861 + GGGGUGGGGGCAGAAGU 17 4710

SCNNlA-862 + UGCAGAGAGAGCAGAGU 17 4711

SCNNlA-863 + AUCAGGAAAGAGAGAGU 17 4712

SCNNlA-864 + CCACUGGCUGCCCAGGU 17 4713

SCNNlA-865 + CUGCCACGGAAUCAGGU 17 4714

SCNNlA-866 + GGAAGACAUCCAGAGGU 17 4715

1206

5535.1 SCNNlA-867 - UCUCCCUCUGUCACGGU 17 4716

SCNNlA-868 + GGUGUGGGGCAGAGGGU 17 4717

SCNNlA-869 + GGACAGAGACAUGGGGU 17 4718

SCNNlA-870 - GUGGGGAAGGGAUGGGU 17 4719

SCNNlA-871 + CCGCGGAUAGAAGAUGU 17 4720

SCNNlA-872 - GAUCUCUUGGUGUAUGU 17 4721

SCNNlA-873 + UAGUAGCAGUACCCUGU 17 4722

SCNNlA-874 + AGAAAGGUGCUCAGUGU 17 4723

SCNNlA-875 - CAUCCCAGGUAGAGUGU 17 4724

SCNNlA-876 + CUCCAUUUCUUAGGUGU 17 4725

SCNNlA-877 - AAACCCUGGACAGACUU 17 4726

SCNNlA-878 + GAAGAAGAUGUUGACUU 17 4727

SCNNlA-879 + AUCGGCUUCGGAACCUU 17 4728

SCNNlA-880 + GAGACCAGUAUCGGCUU 17 4729

SCNNlA-881 + UGGCCACUCCAUUUCUU 17 4730

SCNNlA-882 + UGCCACGGAAUCAGGUU 17 4731

SCNNlA-883 - CAGUGGAGCCUGUGGUU 17 4732

SCNNlA-884 - UCUGCCCCACACCUAAGAAA 20 4733

SCNNlA-885 - UCCAUGCCUGGAAUCAACAA 20 4734

SCNNlA-886 + GGGACCCUCAGGCGCUGCAA 20 4735

SCNNlA-887 + GACCCAUUCCUAGGAAAGAA 20 4736

SCNNlA-888 - UAUGGCGACUGCACCAAGAA 20 4737

SCNNlA-889 + GUCACGCUGGGGAUGGAGAA 20 4738

SCNNlA-890 - CCCCCAUUCUUUCCUAGGAA 20 4739

SCNNlA-891 - CCCAGGUAGAGUGUGGGGAA 20 4740

SCNNlA-892 + GAGUGAAUACACACCUGGAA 20 4741

SCNNlA-893 + UUAAUUUCCGGGUACCUGAA 20 4742

SCNNlA-894 + CCUGCUGUGUGUACUUUGAA 20 4743

SCNNlA-895 + AAAGCCACCAUCAUCCAUAA 20 4744

SCNNlA-896 + GUGUGUACUUUGAAGGGUAA 20 4745

SCNNlA-897 - AGUGACUGGGGCCCGGGUAA 20 4746

SCNNlA-898 - GGCAUCUCUCUGUACCCACA 20 4747

SCNNlA-899 + CUGGGACAAGGACAGAGACA 20 4748

SCNNlA-900 + AGCAGGGCCUGGCUGGGACA 20 4749

SCNNlA-901 - AGGAGAGGUUUCUCACACCA 20 4750

SCNNlA-902 + UGGAGAUGGGCGGGGGCCCA 20 4751

SCNNlA-903 + GGAAGGAGGGGAGGAUGCCA 20 4752

SCNNlA-904 - GUUCCUGGGGUGAGACUCCA 20 4753

SCNNlA-905 + GCCCAGCGUGUCCUCCUCCA 20 4754

SCNNlA-906 - GAAGCUCCCUGCUUGCUCCA 20 4755

SCNNlA-907 - UGGGCCCCCGCCCAUCUCCA 20 4756

SCNNlA-908 + AUCGCCCCCAAGUCUGUCCA 20 4757

1207

5535.1 SCNNlA-909 + AGGGCGCCAUGGAGCAAGCA 20 4758

SCNNlA-910 + CCCAGUCACUGUGGACAGCA 20 4759

SCNNlA-911 + UCAAGGCUGGAGAGGGAGCA 20 4760

SCNNlA-912 - CCAUCAGCAUGAGGAAGGCA 20 4761

SCNNlA-913 + ACCGUUGUUGAUUCCAGGCA 20 4762

SCNNlA-914 + GGCCCAGGGUGGCAUAGGCA 20 4763

SCNNlA-915 - GUCUCCAGGCCGAGGGGGCA 20 4764

SCNNlA-916 + GAAGGGGACACUAACCUGCA 20 4765

SCNNlA-917 + CGGGACCCUCAGGCGCUGCA 20 4766

SCNNlA-918 - CAUCUCCAGGGGGCUCUGCA 20 4767

SCNNlA-919 - GGGGCCCGGGUAAUGGUGCA 20 4768

SCNNlA-920 + CUGCUCUGCGCGCAGCAUCA 20 4769

SCNNlA-921 - UCUACCAGACAUACUCAUCA 20 4770

SCNNlA-922 + AAAGAAUGGGGGUGUCAUCA 20 4771

SCNNlA-923 - CUUCCAGGAGAGCAUGAUCA 20 4772

SCNNlA-924 - AGGGUCCCGCCCCCGCCUCA 20 4773

SCNNlA-925 + AAACCUCUCCUUCCCUCUCA 20 4774

SCNNlA-926 + GGCAGGGGGAGGGGCUGUCA 20 4775

SCNNlA-927 - UUCUGAGUCUCCCUCUGUCA 20 4776

SCNNlA-928 - C A A AG UCAACAUCUUCUUCA 20 4777

SCNNlA-929 + CUGAAGGGGCGAGGGGAAGA 20 4778

SCNNlA-930 - UGUACCUCUCCUCUCACAGA 20 4779

SCNNlA-931 + GCACGACCUACCGUGACAGA 20 4780

SCNNlA-932 + UUUCUUAGGUGUGGGGCAGA 20 4781

SCNNlA-933 + ACACAGAGACUAGAGUCAGA 20 4782

SCNNlA-934 + GGAGGAGGGUGGAGAGGAGA 20 4783

SCNNlA-935 + CCUGCAGAGCCCCCUGGAGA 20 4784

SCNNlA-936 + GGGGCUGUCAAGGCUGGAGA 20 4785

SCNNlA-937 - GGUGUUGUCUGUGGUGGAGA 20 4786

SCNNlA-938 - CCUCUGGGGGGGCCCUGAGA 20 4787

SCNNlA-939 - UCUCUGCUGGUUACUCACGA 20 4788

SCNNlA-940 + GAGGAGAGGUACAUUGACGA 20 4789

SCNNlA-941 + UCUACCUGGGAUGUCACCGA 20 4790

SCNNlA-942 - GGUGAGGCCCGCAGCGCCGA 20 4791

SCNNlA-943 - GAUACUGGUCUCCAGGCCGA 20 4792

SCNNlA-944 - UGUUCCUCAUGCUGCUCCGA 20 4793

SCNNlA-945 + GAGUCCCCCGCAGGUCGCGA 20 4794

SCNNlA-946 + CCGGGUACCUGAAGGGGCGA 20 4795

SCNNlA-947 + AGGCCACGCUACGGGCUCGA 20 4796

SCNNlA-948 + GGGGGCAGAAGUGGGAAGGA 20 4797

SCNNlA-949 + GCUGCCCAGGUUGGACAGGA 20 4798

SCNNlA-950 + UACACACCUGGAAGGGAGGA 20 4799

1208

5535.1 SCNNlA-951 - GACCUCCAUCAGCAUGAGGA 20 4800

SCNNlA-952 - GGUAGAGUGUGGGGAAGGGA 20 4801

SCNNlA-953 + AGCGUGUCCUCCUCCAGGGA 20 4802

SCNNlA-954 - UGGGGGGGCCCUGAGAGGGA 20 4803

SCNNlA-955 + GGGUGGCAUAGGCAGGGGGA 20 4804

SCNNlA-956 + GUAGCUGGUCACGCUGGGGA 20 4805

SCNNlA-957 - UCCCAGGUAGAGUGUGGGGA 20 4806

SCNNlA-958 + GGGUGGGGGCAGAAGUGGGA 20 4807

SCNNlA-959 - CAACCCCCAGGUGGACUGGA 20 4808

SCNNlA-960 + GGAGUGAAUACACACCUGGA 20 4809

SCNNlA-961 - UGCUGACUGGGAGGCCUGGA 20 4810

SCNNlA-962 - CACGGUAGGUCGUGCCUGGA 20 4811

SCNNlA-963 - GAACCUGCCUUUAUGGAUGA 20 4812

SCNNlA-964 + UUUAAUUUCCGGGUACCUGA 20 4813

SCNNlA-965 - GCACCCCUUGCAGCGCCUGA 20 4814

SCNNlA-966 + CCUUGCCUUCCUCAUGCUGA 20 4815

SCNNlA-967 - AUCAGGGGUGGAUGCGGUGA 20 4816

SCNNlA-968 + GCCGGCCACGAGAGUGGUGA 20 4817

SCNNlA-969 + GACUGACCUCUUGUUGUUGA 20 4818

SCNNlA-970 + ACCUGCUGUGUGUACUUUGA 20 4819

SCNNlA-971 - CUACUCUCUCUUUCCUGAUA 20 4820

SCNNlA-972 + CAGCAUCAGGGACAGACCUA 20 4821

SCNNlA-973 + GCAAGCUGGAGGCCACGCUA 20 4822

SCNNlA-974 + U U AU CAGG AAAG AG AG AG U A 20 4823

SCNNlA-975 - CACUUCCACCACCCGAUGUA 20 4824

SCNNlA-976 - GACAGACUUGGGGGCGAUUA 20 4825

SCNNlA-977 - GCAGGAUGAACCUGCCUUUA 20 4826

SCNNlA-978 + GAAGGG UAAAGG U U CU CAAC 20 4827

SCNNlA-979 + CAGAGGACAGGUGGAGGAAC 20 4828

SCNNlA-980 + ACACCGAGGAGCCGAACCAC 20 4829

SCNNlA-981 - AGGCAUCUCUCUGUACCCAC 20 4830

SCNNlA-982 + AGCCGAACCACAGGCUCCAC 20 4831

SCNNlA-983 - GGGCCCGGGUAAUGGUGCAC 20 4832

SCNNlA-984 + CCGAUUUGUUCUGGUUGCAC 20 4833

SCNNlA-985 - GGGUCCCGCCCCCGCCUCAC 20 4834

SCNNlA-986 + GAGUCUCUGGCAGCCUCGAC 20 4835

SCNNlA-987 + GGCCACGCUACGGGCUCGAC 20 4836

SCNNlA-988 - CCCAGGUGGACUGGAAGGAC 20 4837

SCNNlA-989 + UCAGGGCCCCCCCAGAGGAC 20 4838

SCNNlA-990 - ACAACAACCCCCAGGUGGAC 20 4839

SCNNlA-991 + ACUGGCUGCCCAGGUUGGAC 20 4840

SCNNlA-992 - AGGAAGGCAAGGAUGCUGAC 20 4841

1209

5535.1 SCNNlA-993 - CCCCUGCUGUCCACAGUGAC 20 4842

SCNNlA-994 - GAAGGUUCCGAAGCCGAUAC 20 4843

SCNNlA-995 + CAAGCUGGAGGCCACGCUAC 20 4844

SCNNlA-996 - GUGUCCCCUUCCCCGGGUAC 20 4845

SCNNlA-997 + UGAAGGAGCUGUAUUUGUAC 20 4846

SCNNlA-998 - GGUCACCCUCCUGUCCAACC 20 4847

SCNNlA-999 - CAACCAGGUCUCCUGCAACC 20 4848

SCNNlA-1000 + GGUCUGAGGAGAAGUCAACC 20 4849

SCNNlA-1001 - CUUCGCCUGCCGCUUCAACC 20 4850

SCNNlA-1002 + AGCAGGAGUGAAUACACACC 20 4851

SCNNlA-1003 - UGACUUCUCCUCAGACCACC 20 4852

SCNNlA-1004 + UCCAGUCCUUCCAGUCCACC 20 4853

SCNNlA-1005 + ACGCCUGGUUGCAGGAGACC 20 4854

SCNNlA-1006 + UCCCUUCCCCACACUCUACC 20 4855

SCNNlA-1007 - CCCUCGCCCCUUCAGGUACC 20 4856

SCNNlA-1008 + CCUGCCCGUGCACCAUUACC 20 4857

SCNNlA-1009 - UGUGGGUUCAUAGGAAACCC 20 4858

SCNNlA-1010 - UCCCCCUGCCUAUGCCACCC 20 4859

SCNNlA-1011 - UCAGGAGGUAGCCUCCACCC 20 4860

SCNNlA-1012 + CUGCCCGUGCACCAUUACCC 20 4861

SCNNlA-1013 + GCUCCCUGGAGUCUCACCCC 20 4862

SCNNlA-1014 - CUUGCGGGACAACAACCCCC 20 4863

SCNNlA-1015 + CUGGCCCCUGCAGAGCCCCC 20 4864

SCNNlA-1016 - AGGUUAGUGUCCCCUUCCCC 20 4865

SCNNlA-1017 + GGCACUUGGUGAAACAGCCC 20 4866

SCNNlA-1018 + CUGGAGAUGGGCGGGGGCCC 20 4867

SCNNlA-1019 - GUCCACAGUGACUGGGGCCC 20 4868

SCNNlA-1020 - ACAAGAGGUCAGUCCUGCCC 20 4869

SCNNlA-1021 + ACAGGCUCCACUGGCUGCCC 20 4870

SCNNlA-1022 - AUGGCCCUCGGUGACAUCCC 20 4871

SCNNlA-1023 - GCCAGAGACUCUGCCAUCCC 20 4872

SCNNlA-1024 - CAGGUUAGUGUCCCCUUCCC 20 4873

SCNNlA-1025 - UCUCUGUCCUUGUCCCAGCC 20 4874

SCNNlA-1026 + CUGAUGGAGGUCUCCACGCC 20 4875

SCNNlA-1027 + AGGCAGGACUGACUCACGCC 20 4876

SCNNlA-1028 - AGGAUGCUGACUGGGAGGCC 20 4877

SCNNlA-1029 - GGUGGCUUUAACUUGCGGCC 20 4878

SCNNlA-1030 + GCACCCCUGCCCCCUCGGCC 20 4879

SCNNlA-1031 + GCUGGAGAGGGAGCAGGGCC 20 4880

SCNNlA-1032 - UGUCCACAGUGACUGGGGCC 20 4881

SCNNlA-1033 - CUCUGGAUGUCUUCCAUGCC 20 4882

SCNNlA-1034 + GGGAAGGAGGGGAGGAUGCC 20 4883

1210

5535.1 SCNNlA-1035 - AGGCGUGAGUCAGUCCUGCC 20 4884

SCNNlA-1036 - CUGUCACGGUAGGUCGUGCC 20 4885

SCNNlA-1037 - AGUUCCUGGGGUGAGACUCC 20 4886

SCNNlA-1038 + UGCCCAGCGUGUCCUCCUCC 20 4887

SCNNlA-1039 - GUACUGCUACUAUAAGCUCC 20 4888

SCNNlA-1040 - CUGGGCCCCCGCCCAUCUCC 20 4889

SCNNlA-1041 + ACUCCUUGAUCAUGCUCUCC 20 4890

SCNNlA-1042 - CGAAGCCGAUACUGGUCUCC 20 4891

SCNNlA-1043 + AAUCGCCCCCAAGUCUGUCC 20 4892

SCNNlA-1044 + UUCUCACCGUUGUUGAUUCC 20 4893

SCNNlA-1045 - UCUCCACCCUCCUCCCUUCC 20 4894

SCNNlA-1046 - GUGUAUUCACUCCUGCUUCC 20 4895

SCNNlA-1047 - ACUACAGAAAGCACAGUUCC 20 4896

SCNNlA-1048 + CCAGCUCCUCUUUAAUUUCC 20 4897

SCNNlA-1049 + GAGGGCGCCAUGGAGCAAGC 20 4898

SCNNlA-1050 + GGGGUUGUUGUCCCGCAAGC 20 4899

SCNNlA-1051 + GAUCAUGCUCUCCUGGAAGC 20 4900

SCNNlA-1052 - CCCU U CAAAG U ACACACAG C 20 4901

SCNNlA-1053 + CCCCAGUCACUGUGGACAGC 20 4902

SCNNlA-1054 + GCGCUGCGGGCCUCACCAGC 20 4903

SCNNlA-1055 + UGAGGAACAUGAUGACCAGC 20 4904

SCNNlA-1056 - CUGGAAGAUCGGCUUCCAGC 20 4905

SCNNlA-1057 + GUGAGUAACCAGCAGAGAGC 20 4906

SCNNlA-1058 - CCCGGAAAUUAAAGAGGAGC 20 4907

SCNNlA-1059 - UAAAGAGGAGCUGGAGGAGC 20 4908

SCNNlA-1060 + GUCAAGGCUGGAGAGGGAGC 20 4909

SCNNlA-1061 + GUCGCGACGGCUGCGGGAGC 20 4910

SCNNlA-1062 + ACCAGCAGAGAGCUGGUAGC 20 4911

SCNNlA-1063 - AUCCCUGGAGGAGGACACGC 20 4912

SCNNlA-1064 + GAGCUGGUAGCUGGUCACGC 20 4913

SCNNlA-1065 + GGUGCGGCAGAGUCCCCCGC 20 4914

SCNNlA-1066 + CCACCAUCAUCCAUAAAGGC 20 4915

SCNNlA-1067 + GGGGGAGGGGCUGUCAAGGC 20 4916

SCNNlA-1068 + CUCGACGGGCCCCGUGAGGC 20 4917

SCNNlA-1069 + GGGCCCAGGGUGGCAUAGGC 20 4918

SCNNlA-1070 + GGAGACCUGGUUGAAGCGGC 20 4919

SCNNlA-1071 + CUUGUGGCUGGGACCAGGGC 20 4920

SCNNlA-1072 - CCGGGUAAUGGUGCACGGGC 20 4921

SCNNlA-1073 - GGUCUCCAGGCCGAGGGGGC 20 4922

SCNNlA-1074 + GGGCCCCGUGAGGCGGGGGC 20 4923

SCNNlA-1075 + AGAGCCCCCUGGAGAUGGGC 20 4924

SCNNlA-1076 + GAGAGGGAGCAGGGCCUGGC 20 4925

1211

5535.1 SCNNlA-1077 - UCCUUCACCACUCUCGUGGC 20 4926

SCNNlA-1078 - CCAAGUGCCGGAAGCCAUGC 20 4927

SCNNlA-1079 - CCGCAGCCGUCGCGACCUGC 20 4928

SCNNlA-1080 - UGAGCUCGUCUUUGACCUGC 20 4929

SCNNlA-1081 + GGCGGGCCCCUCGGCGCUGC 20 4930

SCNNlA-1082 + CCGCAGGUCGCGACGGCUGC 20 4931

SCNNlA-1083 - CCAUCUCCAGGGGGCUCUGC 20 4932

SCNNlA-1084 - ACCAGCUACCAGCUCUCUGC 20 4933

SCNNlA-1085 - UGGGCUGUUUCACCAAGUGC 20 4934

SCNNlA-1086 - UAGCGUGGCCUCCAGCUUGC 20 4935

SCNNlA-1087 + ACUGACUCACGCCUGGUUGC 20 4936

SCNNlA-1088 + UAUAGCAGUUUCCAUACAUC 20 4937

SCNNlA-1089 + UCUGCUCUGCGCGCAGCAUC 20 4938

SCNNlA-1090 + UGUUCUGUCGCGAUAGCAUC 20 4939

SCNNlA-1091 - UUCUACCAGACAUACUCAUC 20 4940

SCNNlA-1092 + AGUGAGAGUAAUUCCUUAUC 20 4941

SCNNlA-1093 - ACAAGAACAACUCCAACCUC 20 4942

SCNNlA-1094 + GAGGCGGGGGCGGGACCCUC 20 4943

SCNNlA-1095 - CAGUUCCUCCACCUGUCCUC 20 4944

SCNNlA-1096 - CCGAGGGGGCAGGGGUGCUC 20 4945

SCNNlA-1097 + GAAACCUCUCCUUCCCUCUC 20 4946

SCNNlA-1098 + UCCAGGGAUGGCAGAGUCUC 20 4947

SCNNlA-1099 + GGGGCGAGGGGAAGAGGGUC 20 4948

SCNNlA-1100 + CCACCCCUGAUGAGUAUGUC 20 4949

SCNNlA-1101 - CCUCUUCCCCUCGCCCCUUC 20 4950

SCNNlA-1102 + ACACUAACCUGCAUGGCUUC 20 4951

SCNNlA-1103 + AGUCACAGUACUCCACGUUC 20 4952

SCNNlA-1104 + AG AAG CAGUCCGAUUUGUUC 20 4953

SCNNlA-1105 + UCCAGCUCCUCUUUAAUUUC 20 4954

SCNNlA-1106 - CAGGUACCCGGAAAUUAAAG 20 4955

SCNNlA-1107 - AU U ACACCG U CAACAACAAG 20 4956

SCNNlA-1108 + GGACCCUCAGGCGCUGCAAG 20 4957

SCNNlA-1109 + ACAUGGGGUGGGGGCAGAAG 20 4958

SCNNlA-1110 + CCUGAAGGGGCGAGGGGAAG 20 4959

SCNNlA-1111 + GGAUGUUGAUGUAGUGGAAG 20 4960

SCNNlA-1112 + UAAUUUCCGGGUACCUGAAG 20 4961

SCNNlA-1113 + UGCAGGAGACCUGGUUGAAG 20 4962

SCNNlA-1114 + GGCACGACCUACCGUGACAG 20 4963

SCNNlA-1115 + CCCUCUCAGGGCCCCCCCAG 20 4964

SCNNlA-1116 - UGUCCAACCUGGGCAGCCAG 20 4965

SCNNlA-1117 + CAGGCAUGGAAGACAUCCAG 20 4966

SCNNlA-1118 - GGGCCCCCGCCCAUCUCCAG 20 4967

1212

5535.1 SCNNlA-1119 + CCAGUCACUGUGGACAGCAG 20 4968

SCNNlA-1120 + GCCCAGGGUGGCAUAGGCAG 20 4969

SCNNlA-1121 - UCUCCAGGCCGAGGGGGCAG 20 4970

SCNNlA-1122 + AUUUCUUAGGUGUGGGGCAG 20 4971

SCNNlA-1123 - AUCUCCAGGGGGCUCUGCAG 20 4972

SCNNlA-1124 - CUACCAGACAUACUCAUCAG 20 4973

SCNNlA-1125 + GACACAGAGACUAGAGUCAG 20 4974

SCNNlA-1126 + CACAGAGACUAGAGUCAGAG 20 4975

SCNNlA-1127 + GCGGGAGCCGGCCACGAGAG 20 4976

SCNNlA-1128 - GUGAGGCCCGCAGCGCCGAG 20 4977

SCNNlA-1129 - AUACUGGUCUCCAGGCCGAG 20 4978

SCNNlA-1130 + CGGGUACCUGAAGGGGCGAG 20 4979

SCNNlA-1131 - GGGCCCUGAGAGGGAAGGAG 20 4980

SCNNlA-1132 + GGGGCAGAAGUGGGAAGGAG 20 4981

SCNNlA-1133 + GGGAGGAGGGUGGAGAGGAG 20 4982

SCNNlA-1134 + GUGACCAUCUGUGAGAGGAG 20 4983

SCNNlA-1135 - GGGUGGAUGCGGUGAGGGAG 20 4984

SCNNlA-1136 + GGUGGCAUAGGCAGGGGGAG 20 4985

SCNNlA-1137 - CCCACACCUAAGAAAUGGAG 20 4986

SCNNlA-1138 + AGGGGCUGUCAAGGCUGGAG 20 4987

SCNNlA-1139 + UGGAAGGGAGGAGGGUGGAG 20 4988

SCNNlA-1140 - UCCUCUGGGGGGGCCCUGAG 20 4989

SCNNlA-1141 + GGAGGGUGACCAUCUGUGAG 20 4990

SCNNlA-1142 + AGCAUCAGGGACAGACCUAG 20 4991

SCNNlA-1143 + UCGACAGGAUGUUGAUGUAG 20 4992

SCNNlA-1144 - CUAUCCGCGGCCCCAGAACG 20 4993

SCNNlA-1145 - GGUCCCGCCCCCGCCUCACG 20 4994

SCNNlA-1146 + CUCCACCACAGACAACACCG 20 4995

SCNNlA-1147 + CUCUACCUGGGAUGUCACCG 20 4996

SCNNlA-1148 - UGGUGAGGCCCGCAGCGCCG 20 4997

SCNNlA-1149 - CGAUACUGGUCUCCAGGCCG 20 4998

SCNNlA-1150 + UACUCCACGUUCUGGGGCCG 20 4999

SCNNlA-1151 - GUGCCUACAUCUUCUAUCCG 20 5000

SCNNlA-1152 - UGAGGCCCAACCUGAUUCCG 20 5001

SCNNlA-1153 - GGCCCGUCGAGCCCGUAGCG 20 5002

SCNNlA-1154 + UCGACGGGCCCCGUGAGGCG 20 5003

SCNNlA-1155 + UCCGGGUACCUGAAGGGGCG 20 5004

SCNNlA-1156 + GAGCCCCCUGGAGAUGGGCG 20 5005

SCNNlA-1157 - CUUUAACUUGCGGCCUGGCG 20 5006

SCNNlA-1158 - CGCAGCCGUCGCGACCUGCG 20 5007

SCNNlA-1159 - CAGCUCCUUCACCACUCUCG 20 5008

SCNNlA-1160 - ACUACAUCAACAUCCUGUCG 20 5009

1213

5535.1 SCNNlA-1161 + UGGGGGCAGAAGUGGGAAGG 20 5010

SCNNlA-1162 + GGGCCCCCCCAGAGGACAGG 20 5011

SCNNlA-1163 + GGCUGCCCAGGUUGGACAGG 20 5012

SCNNlA-1164 - GCGGGACAACAACCCCCAGG 20 5013

SCNNlA-1165 + ACUUGGUGAAACAGCCCAGG 20 5014

SCNNlA-1166 - GGCCCCCGCCCAUCUCCAGG 20 5015

SCNNlA-1167 + CCCAGGGUGGCAUAGGCAGG 20 5016

SCNNlA-1168 - AGGGGGCAGGGGUGCUCAGG 20 5017

SCNNlA-1169 - UACUGGUCUCCAGGCCGAGG 20 5018

SCNNlA-1170 + AUACACACCUGGAAGGGAGG 20 5019

SCNNlA-1171 - GACUCUGCCAUCCCUGGAGG 20 5020

SCNNlA-1172 + GCUCGACGGGCCCCGUGAGG 20 5021

SCNNlA-1173 + CGACGGGCCCCGUGAGGCGG 20 5022

SCNNlA-1174 + AGCCCCCUGGAGAUGGGCGG 20 5023

SCNNlA-1175 - GCAGCCGUCGCGACCUGCGG 20 5024

SCNNlA-1176 + UGAAUACACACCUGGAAGGG 20 5025

SCNNlA-1177 + AGAUGGGCGGGGGCCCAGGG 20 5026

SCNNlA-1178 + AGGAGGGGAGGAUGCCAGGG 20 5027

SCNNlA-1179 + CUUAGGUGUGGGGCAGAGGG 20 5028

SCNNlA-1180 + ACACCUGGAAGGGAGGAGGG 20 5029

SCNNlA-1181 + AGCAGUUUCCAUACAUCGGG 20 5030

SCNNlA-1182 - CCAGACAUACUCAUCAGGGG 20 5031

SCNNlA-1183 + GCAGAAGUGGGAAGGAGGGG 20 5032

SCNNlA-1184 + AGGGUGGCAUAGGCAGGGGG 20 5033

SCNNlA-1185 + CGGGCCCCGUGAGGCGGGGG 20 5034

SCNNlA-1186 + ACAAGGACAGAGACAUGGGG 20 5035

SCNNlA-1187 - CCUCCACCUGUCCUCUGGGG 20 5036

SCNNlA-1188 + CAGAGCCCCCUGGAGAUGGG 20 5037

SCNNlA-1189 - GAGUGUGGGGAAGGGAUGGG 20 5038

SCNNlA-1190 - AGGCAAGGAUGCUGACUGGG 20 5039

SCNNlA-1191 - UCCUCCACCUGUCCUCUGGG 20 5040

SCNNlA-1192 + CCAUUCCUAGGAAAGAAUGG 20 5041

SCNNlA-1193 - CCUGCCUUUAUGGAUGAUGG 20 5042

SCNNlA-1194 + UGCCUUCCUCAUGCUGAUGG 20 5043

SCNNlA-1195 + AGUCCUUCCAGUCCACCUGG 20 5044

SCNNlA-1196 - AGAGACUCUGCCAUCCCUGG 20 5045

SCNNlA-1197 + GUUGUUGUCCCGCAAGCUGG 20 5046

SCNNlA-1198 - GGAAAUUAAAGAGGAGCUGG 20 5047

SCNNlA-1199 - UUCCUCCACCUGUCCUCUGG 20 5048

SCNNlA-1200 + CCCCCCCAGAGGACAGGUGG 20 5049

SCNNlA-1201 + AGGGGAGGAUGCCAGGGUGG 20 5050

SCNNlA-1202 + AGUUUCCAUACAUCGGGUGG 20 5051

1214

5535.1 SCNNlA-1203 + AGGACAGAGACAUGGGGUGG 20 5052

SCNNlA-1204 - UGUGGGGAAGGGAUGGGUGG 20 5053

SCNNlA-1205 - CUCCUCGGUGUUGUCUGUGG 20 5054

SCNNlA-1206 - G AAACCCUGGACAGACU UGG 20 5055

SCNNlA-1207 + CCCAUUCCUAGGAAAGAAUG 20 5056

SCNNlA-1208 + GGGACAAGGACAGAGACAUG 20 5057

SCNNlA-1209 + GGAACCUUCGGAGCAGCAUG 20 5058

SCNNlA-1210 - UGGAGACCUCCAUCAGCAUG 20 5059

SCNNlA-1211 - AUACUCAUCAGGGGUGGAUG 20 5060

SCNNlA-1212 + AGAGCGUCUGCUCUGUGAUG 20 5061

SCNNlA-1213 + UACCCGGGCCCCAGUCACUG 20 5062

SCNNlA-1214 - CCUGCUGUCCACAGUGACUG 20 5063

SCNNlA-1215 + CAGUCCUUCCAGUCCACCUG 20 5064

SCNNlA-1216 - CCCGCAGCCGUCGCGACCUG 20 5065

SCNNlA-1217 + CUUAUAGUAGCAGUACCCUG 20 5066

SCNNlA-1218 - UGGGCAGCCAGUGGAGCCUG 20 5067

SCNNlA-1219 - CGCACCCCUUGCAGCGCCUG 20 5068

SCNNlA-1220 - UACAGAAAGCACAGUUCCUG 20 5069

SCNNlA-1221 + GCUGGUAGCUGGUCACGCUG 20 5070

SCNNlA-1222 + GGGCGGGCCCCUCGGCGCUG 20 5071

SCNNlA-1223 + CCCGCAGGUCGCGACGGCUG 20 5072

SCNNlA-1224 - GUUCCUCCACCUGUCCUCUG 20 5073

SCNNlA-1225 + GAAACAGCCCAGGUGGUCUG 20 5074

SCNNlA-1226 - CGGCUCCUCGGUGUUGUCUG 20 5075

SCNNlA-1227 + UCACAGUACUCCACGUUCUG 20 5076

SCNNlA-1228 - GUGACAUCCCAGGUAGAGUG 20 5077

SCNNlA-1229 - GAGAGCAUGAUCAAGGAGUG 20 5078

SCNNlA-1230 + CGGGCUCGACGGGCCCCGUG 20 5079

SCNNlA-1231 - C AAAG U AC ACAC AG C AG G U G 20 5080

SCNNlA-1232 + GCCACUCCAUUUCUUAGGUG 20 5081

SCNNlA-1233 - CAUCAGGGGUGGAUGCGGUG 20 5082

SCNNlA-1234 + CUCAGGCGCUGCAAGGGGUG 20 5083

SCNNlA-1235 + AAGGACAGAGACAUGGGGUG 20 5084

SCNNlA-1236 - GUGUGGGGAAGGGAUGGGUG 20 5085

SCNNlA-1237 - AGAUCGGCUUCCAGCUGGUG 20 5086

SCNNlA-1238 - GACAUCCCAGGUAGAGUGUG 20 5087

SCNNlA-1239 + CACUCCAUUUCUUAGGUGUG 20 5088

SCNNlA-1240 - AUGAUGGUGGCUUUAACUUG 20 5089

SCNNlA-1241 - GGAAACCCUGGACAGACUUG 20 5090

SCNNlA-1242 - GUAGCGUGGCCUCCAGCUUG 20 5091

SCNNlA-1243 - CCAGUGCAACCAGAACAAAU 20 5092

SCNNlA-1244 + ACCCAUUCCUAGGAAAGAAU 20 5093

1215

5535.1 SCNNlA-1245 + GACAGAGGGAGACUCAGAAU 20 5094

SCNNlA-1246 - CCCCAUUCUUUCCUAGGAAU 20 5095

SCNNlA-1247 + UGGGACAAGGACAGAGACAU 20 5096

SCNNlA-1248 + GUAUAGCAGUUUCCAUACAU 20 5097

SCNNlA-1249 + GCGGGGGCCCAGGGUGGCAU 20 5098

SCNNlA-1250 - CUUGGUGUAUGUGGGUUCAU 20 5099

SCNNlA-1251 - GACUGGAAGGACUGGAAGAU 20 5100

SCNNlA-1252 + CUGCAGAGCCCCCUGGAGAU 20 5101

SCNNlA-1253 + AGGAGAGGUACAUUGACGAU 20 5102

SCNNlA-1254 - GUAGAGUGUGGGGAAGGGAU 20 5103

SCNNlA-1255 + CUCGGCCUGGAGACCAGUAU 20 5104

SCNNlA-1256 + CCUGCAUGGCUUCCGGCACU 20 5105

SCNNlA-1257 - UAGGAAACCCUGGACAGACU 20 5106

SCNNlA-1258 - GGAAGGCAAGGAUGCUGACU 20 5107

SCNNlA-1259 - CCCUGCUGUCCACAGUGACU 20 5108

SCNNlA-1260 - GUCACCCUCCUGUCCAACCU 20 5109

SCNNlA-1261 - GACUUCUCCUCAGACCACCU 20 5110

SCNNlA-1262 + CCAGUCCUUCCAGUCCACCU 20 5111

SCNNlA-1263 + GCAGCAUCAGGGACAGACCU 20 5112

SCNNlA-1264 + CCCUUCCCCACACUCUACCU 20 5113

SCNNlA-1265 - CCCCCUGCCUAUGCCACCCU 20 5114

SCNNlA-1266 - UCUGCUCUCUCUGCACCCCU 20 5115

SCNNlA-1267 + CCUGAGCACCCCUGCCCCCU 20 5116

SCNNlA-1268 - UGGUUACUCACGAUGGCCCU 20 5117

SCNNlA-1269 - GAGCCUGUGGUUCGGCUCCU 20 5118

SCNNlA-1270 + CAUCUGGAAGACCCAUUCCU 20 5119

SCNNlA-1271 - CUACAGAAAG CACAG U U CCU 20 5120

SCNNlA-1272 - UGACACCCCCAUUCUUUCCU 20 5121

SCNNlA-1273 - UCCCUGGAGGAGGACACGCU 20 5122

SCNNlA-1274 + AGCUGGUAGCUGGUCACGCU 20 5123

SCNNlA-1275 + AGAGGGAGCAGGGCCUGGCU 20 5124

SCNNlA-1276 - AGUUCCUCCACCUGUCCUCU 20 5125

SCNNlA-1277 + AGGAACAUCACUGCCAUUCU 20 5126

SCNNlA-1278 + GUCACAGUACUCCACGUUCU 20 5127

SCNNlA-1279 + CAUGGGGUGGGGGCAGAAGU 20 5128

SCNNlA-1280 + GGGUGCAGAGAGAGCAGAGU 20 5129

SCNNlA-1281 + CUUAUCAGGAAAGAGAGAGU 20 5130

SCNNlA-1282 + GCUCCACUGGCUGCCCAGGU 20 5131

SCNNlA-1283 + UGGCUGCCACGGAAUCAGGU 20 5132

SCNNlA-1284 + CAUGGAAGACAUCCAGAGGU 20 5133

SCNNlA-1285 - GAGUCUCCCUCUGUCACGGU 20 5134

SCNNlA-1286 + UUAGGUGUGGGGCAGAGGGU 20 5135

1216

5535.1 SCNNlA-1287 + CAAGGACAGAGACAUGGGGU 20 5136

SCNNlA-1288 - AGUGUGGGGAAGGGAUGGGU 20 5137

SCNNlA-1289 + GGGCCGCGGAUAGAAGAUGU 20 5138

SCNNlA-1290 - UCUGAUCUCUUGGUGUAUGU 20 5139

SCNNlA-1291 + UUAUAGUAGCAGUACCCUGU 20 5140

SCNNlA-1292 + UGGAGAAAGGUGCUCAGUGU 20 5141

SCNNlA-1293 - UGACAUCCCAGGUAGAGUGU 20 5142

SCNNlA-1294 + CCACUCCAUUUCUUAGGUGU 20 5143

SCNNlA-1295 - AGGAAACCCUGGACAGACUU 20 5144

SCNNlA-1296 + CUUGAAGAAGAUGUUGACUU 20 5145

SCNNlA-1297 + AGUAUCGGCUUCGGAACCUU 20 5146

SCNNlA-1298 + CUGGAGACCAGUAUCGGCUU 20 5147

SCNNlA-1299 + CUUUGGCCACUCCAUUUCUU 20 5148

SCNNlA-1300 + GGCUGCCACGGAAUCAGGUU 20 5149

SCNNlA-1301 - AGCCAGUGGAGCCUGUGGUU 20 5150

Table 44A provides exemplary targeting domains for knocking out the SCNN1A gene selected according to the first tier parameters. The targeting domains bind within the first 500 bp of the coding sequence (e.g., with 500 bp downstream from the start codon), have a high level of orthogonality, start with a 5'G, and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 44A

1217

5535.1 SCNN lA-1313 + GGUAUGGGCUGCAGAGGUC 19 5162

SCNN lA-1314 + GACCUGGUAUGGGCUGCAGAGGUC 24 5163

SCNN lA-1315 + GAUACCUCCCCUUGGAAGGGACAG 24 5164

SCNN lA-1316 + GUGCUGGGAGCACACCAG 18 5165

SCNN lA-1317 + GUUGUGCUGGGAGCACACCAG 21 5166

SCNN lA-1318 + GGUUGUGCUGGGAGCACACCAG 22 5167

SCNN lA-1319 + GCGGUUGUGCUGGGAGCACACCAG 24 5168

SCNN lA-1320 + GUACUCUCCGAAAAGCAGG 19 5169

SCNN lA-1321 + GAAGUACUCUCCGAAAAGCAGG 22 5170

SCNN lA-1322 + GAUUGGGGAGAGCAAGGGU 19 5171

SCNN lA-1323 + GGAUUGGGGAGAGCAAGGGU 20 5172

SCNN lA-1324 + GUGGAUUGGGGAGAGCAAGGGU 22 5173

SCNN lA-1325 + GAGUGGAUUGGGGAGAGCAAGGGU 24

5174

SCNN lA-1326 + GAGGGACUAACCGACCUGU 19 5175

SCNN lA-1327 + GCAGAGGGACUAACCGACCUGU 22 5176

SCNN lA-1328 + GGCAGAGGGACUAACCGACCUGU 23 5177

SCNN lA-1329 + GGGCAGAGGGACUAACCGACCUGU 24 5178

SCNN lA-1330 + GCGGGGAAGACGAGCU UGU 19 5179

SCNN lA-1331 + GACUAACCGACCUGUAGGGAUU 22 5180

SCNN lA-1332 + GGACUAACCGACCUGUAGGGAUU 23 5181

SCNN lA-1333 + GGGACUAACCGACCUGUAGGGAUU 24 5182

SCNN lA-1334 - GCGGAGGAGGAGGCCCUGA 19 5183

SCN N lA-189 - GGCGGAGGAGGAGGCCCUGA 20 819

SCNN lA-1335 - GGCCAGGGGCAGCCUCAC 18 5184

SCNN lA-1336 - GCAGCCUCACUCGGGUUCC 19 5185

SCN N lA-348 - GGCAGCCUCACUCGGGU UCC 20 4197

SCN N lA-197 - GCAAUUCGGCCUGCU UUUCG 20 826

SCNN lA-1337 - GGCAAUUCGGCCUGCU UUUCG 21 5186

SCNN lA-1338 - GCUCCUACCGAGAGCUCU 18 5187

SCN N lA-437 - GUAAGCAAGGGAACCUGGUU 20 4286

SCNN lA-1339 - GGUAAGCAAGGGAACCUGGUU 21 5188

Table 44B provides exemplary targeting domains for knocking out the SCNN1A gene selected according to the second tier parameters. The targeting domains bind within the first 500 bp of the coding sequence (e.g., with 500 bp downstream from the start codon), have a high level of orthogonality and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

1218

5535.1 Table 44B

1219

5535.1 SCNNlA-1375 + UGAAGUACUCUCCGAAAAGCAGG 23 5224

SCNNlA-1376 + CUGAAGUACUCUCCG A A A AG C AG G 24 5225

SCNNlA-1377 + AUUGGGGAGAGCAAGGGU 18 5226

SCNNlA-1378 + UGGAUUGGGGAGAGCAAGGGU 21 5227

SCNNlA-1379 + AGUGGAUUGGGGAGAGCAAGGGU 23 5228

SCNNlA-1380 + AGGGACUAACCGACCUGU 18 5229

SCNNlA-424 + AGAGGGACUAACCGACCUGU 20 4273

SCNNlA-1381 + CAGAGGGACUAACCGACCUGU 21 5230

SCNNlA-1382 + CGGGGAAGACGAGCUUGU 18 5231

SCNNlA-237 + UGCGGGGAAGACGAGCUUGU 20 857

SCNNlA-1383 + CUGCGGGGAAGACGAGCUUGU 21 5232

SCNNlA-1384 + ACUGCGGGGAAGACGAGCUUGU 22 5233

SCNNlA-1385 + CACUGCGGGGAAGACGAGCUUGU 23 5234

SCNNlA-1386 + UCACUGCGGGGAAGACGAGCUUGU 24 5235

SCNNlA-1387 + AACCGACCUGUAGGGAUU 18 5236

SCNNlA-1388 + UAACCGACCUGUAGGGAUU 19 5237

SCNNlA-1389 + CUAACCGACCUGUAGGGAUU 20 5238

SCNNlA-1390 + ACUAACCGACCUGUAGGGAUU 21 5239

SCNNlA-1391 - CGGAGGAGGAGGCCCUGA 18 5240

SCNNlA-1392 - UGGCCAGGGGCAGCCUCAC 19 5241

SCNNlA-1393 - AUGGCCAGGGGCAGCCUCAC 20 5242

SCNNlA-1394 - CAGCCUCACUCGGGUUCC 18 5243

SCNNlA-1395 - AAUUCGGCCUGCUUUUCG 18 5244

SCNNlA-1396 - CAAUUCGGCCUGCUUUUCG 19 5245

SCNNlA-1397 - UGGCAAUUCGGCCUGCUUUUCG 22 5246

SCNNlA-1398 - CUGGCAAUUCGGCCUGCUUUUCG 23 5247

SCNNlA-1399 - ACUGGCAAUUCGGCCUGCUUUUCG 24 5248

SCNNlA-1400 - CGCUCCUACCGAGAGCUCU 19 5249

SCNNlA-192 - CCGCUCCUACCGAGAGCUCU 20 822

SCNNlA-1401 - ACCGCUCCUACCGAGAGCUCU 21 5250

SCNNlA-1402 - CACCGCUCCUACCGAGAGCUCU 22 5251

SCNNlA-1403 - CCACCGCUCCUACCGAGAGCUCU 23 5252

SCNNlA-1404 - UCCACCGCUCCUACCGAGAGCUCU 24 5253

SCNNlA-1405 - AAGCAAGGGAACCUGGUU 18 5254

SCNNlA-1406 - UAAGCAAGGGAACCUGGUU 19 5255

SCNNlA-1407 - AGGUAAGCAAGGGAACCUGGUU 22 5256

SCNNlA-1408 - AAGGUAAGCAAGGGAACCUGGUU 23 5257

SCNNlA-1409 - C A AG G U A AG C A AG GGAACCUGGUU 24 5258

Table 44C provides exemplary targeting domains for knocking out the SCNNIA gene selected according to the third tier parameters. The targeting domains bind within the first 500 bp

1220

5535.1 of the coding sequence (e.g., with 500 bp downstream from the start codon), have a high level of orthogonality and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 44C

1221

5535.1 SCNNlA-1438 - GCAUGGCCAGGGGCAGCCUCAC 22 5287

SCNNlA-1439 - GGCAUGGCCAGGGGCAGCCUCAC 23 5288

SCNNlA-1440 - GGGCAUGGCCAGGGGCAGCCUCAC 24 5289

SCNNlA-1441 - GGGCAGCCUCACUCGGGUUCC 21 5290

SCNNlA-1442 - GGGGCAGCCUCACUCGGGUUCC 22 5291

SCNNlA-1443 - AGGGGCAGCCUCACUCGGGUUCC 23 5292

SCNNlA-1444 - CAGGGGCAGCCUCACUCGGGUUCC 24 5293

Table 44D provides exemplary targeting domains for knocking out the SCNN1A gene selected according to the fourth tier parameters. The targeting domains bind within the first 500 bp of the coding sequence (e.g., with 500 bp downstream from the start codon), have a high level of orthogonality and PAM is NNGRRV. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 44D

1222

5535.1 SCNNlA-1464 + UUGUUCCCCUUCAUGAGCCCUGGA 24 5313

SCNNlA-1465 + CAUGAGCCCCGGAGUGGA 18 5314

SCNNlA-1466 + UCAUGAGCCCCGGAGUGGA 19 5315

SCNNlA-1467 + UUCAUGAGCCCCGGAGUGGA 20 5316

SCNNlA-1468 + CUUCAUGAGCCCCGGAGUGGA 21 5317

SCNNlA-1469 + CCUUCAUGAGCCCCGGAGUGGA 22 5318

SCNNlA-1470 + CCCUUCAUGAGCCCCGGAGUGGA 23 5319

SCNNlA-1471 + CCCCUUCAUGAGCCCCGGAGUGGA 24 5320

SCNNlA-1472 + AUGAUACCUCCCCUUGGA 18 5321

SCNNlA-1473 + CAUGAUACCUCCCCUUGGA 19 5322

SCNNlA-399 + UCAUGAUACCUCCCCUUGGA 20 4248

SCNNlA-1474 + CUCAUGAUACCUCCCCUUGGA 21 5323

SCNNlA-1475 + GCUCAUGAUACCUCCCCUUGGA 22 5324

SCNNlA-1476 + UGCUCAUGAUACCUCCCCUUGGA 23 5325

SCNNlA-1477 + CUGCUCAUGAUACCUCCCCUUGGA 24 5326

SCNNlA-1478 + GUGUUGUUGCAGAAGAAC 18 5327

SCNNlA-1479 + GGUGUUGUUGCAGAAGAAC 19 5328

SCNNlA-220 + UGGUGUUGUUGCAGAAGAAC 20 843

SCNNlA-1480 + GUGGUGUUGUUGCAGAAGAAC 21 5329

SCNNlA-1481 + GGUGGUGUUGUUGCAGAAGAAC 22 5330

SCNNlA-1482 + UGGUGGUGUUGUUGCAGAAGAAC 23 5331

SCNNlA-1483 + AUGGUGGUGUUGUUGCAGAAGAAC 24

5332

SCNNlA-1484 + UGCCCUCUCCCAUCACCC 18 5333

SCNNlA-1485 + GUGCCCUCUCCCAUCACCC 19 5334

SCNNlA-1486 + AGUGCCCUCUCCCAUCACCC 20 5335

SCNNlA-1487 + GAGUGCCCUCUCCCAUCACCC 21 5336

SCNNlA-1488 + UGAGUGCCCUCUCCCAUCACCC 22 5337

SCNNlA-1489 + CUGAGUGCCCUCUCCCAUCACCC 23 5338

SCNNlA-1490 + CCUGAGUGCCCUCUCCCAUCACCC 24 5339

SCNNlA-1491 + GCCCUCUCCCAUCACCCC 18 5340

SCNNlA-1492 + UGCCCUCUCCCAUCACCCC 19 5341

SCNNlA-346 + GUGCCCUCUCCCAUCACCCC 20 4195

SCNNlA-1493 + AGUGCCCUCUCCCAUCACCCC 21 5342

SCNNlA-1494 + GAGUGCCCUCUCCCAUCACCCC 22 5343

SCNNlA-1495 + UGAGUGCCCUCUCCCAUCACCCC 23 5344

SCNNlA-1496 + CUGAGUGCCCUCUCCCAUCACCCC 24 5345

SCNNlA-1497 + UGCUCAUGAUACCUCCCC 18 5346

SCNNlA-1498 + CUGCUCAUGAUACCUCCCC 19 5347

SCNNlA-1499 + ACUGCUCAUGAUACCUCCCC 20 5348

SCNNlA-1500 + UACUGCUCAUGAUACCUCCCC 21 5349

SCNNlA-1501 + AUACUGCUCAUGAUACCUCCCC 22 5350

1223

5535.1 SCNNlA-1502 + GAUACUGCUCAUGAUACCUCCCC 23 5351

SCNNlA-1503 + UGAUACUGCUCAUGAUACCUCCCC 24 5352

SCNNlA-1504 + UGUUCCCCUUCAUGAGCC 18 5353

SCNNlA-1505 + UUGUUCCCCUUCAUGAGCC 19 5354

SCNNlA-207 + CUUGUUCCCCUUCAUGAGCC 20 834

SCNNlA-1506 + GCUUGUUCCCCUUCAUGAGCC 21 5355

SCNNlA-1507 + AGCUUGUUCCCCUUCAUGAGCC 22 5356

SCNNlA-1508 + CAGCUUGUUCCCCUUCAUGAGCC 23 5357

SCNNlA-1509 + CCAGCUUGUUCCCCUUCAUGAGCC 24 5358

SCNNlA-1510 + CGCUUGUUCCCCUUCAUGAGCC 22 5359

SCNNlA-1511 + ACGCUUGUUCCCCUUCAUGAGCC 23 5360

SCNNlA-1512 + CACGCUUGUUCCCCUUCAUGAGCC 24 5361

SCNNlA-1513 + AGGGCCUCCUCCUCCGCC 18 5362

SCNNlA-1514 + CAGGGCCUCCUCCUCCGCC 19 5363

SCNNlA-213 + UCAGGGCCUCCUCCUCCGCC 20 838

SCNNlA-1515 + AUCAGGGCCUCCUCCUCCGCC 21 5364

SCNNlA-1516 + GAUCAGGGCCUCCUCCUCCGCC 22 5365

SCNNlA-1517 + CGAUCAGGGCCUCCUCCUCCGCC 23 5366

SCNNlA-1518 + UCGAUCAGGGCCUCCUCCUCCGCC 24 5367

SCNNlA-1519 + CAGAGCCACAGCACUGCC 18 5368

SCNNlA-1520 + GCAGAGCCACAGCACUGCC 19 5369

SCNNlA-228 + UGCAGAGCCACAGCACUGCC 20 849

SCNNlA-1521 + GUGCAGAGCCACAGCACUGCC 21 5370

SCNNlA-1522 + GGUGCAGAGCCACAGCACUGCC 22 5371

SCNNlA-1523 + AGGUGCAGAGCCACAGCACUGCC 23 5372

SCNNlA-1524 + AAGGUGCAGAGCCACAGCACUGCC 24 5373

SCNNlA-1525 + UCCAGCUUGUUCCCCUCC 18 5374

SCNNlA-1526 + CUCCAGCUUGUUCCCCUCC 19 5375

SCNNlA-200 + CCUCCAGCUUGUUCCCCUCC 20 829

SCNNlA-1527 + UCCUCCAGCUUGUUCCCCUCC 21 5376

SCNNlA-1528 + CUCCUCCAGCUUGUUCCCCUCC 22 5377

SCNNlA-1529 + GCUCCUCCAGCUUGUUCCCCUCC 23 5378

SCNNlA-1530 + UGCUCCUCCAGCUUGUUCCCCUCC 24 5379

SCNNlA-1531 + GGUGCAGAUGGUCACUGC 18 5380

SCNNlA-1532 + GGGUGCAGAUGGUCACUGC 19 5381

SCNNlA-38 + AGGGUGCAGAUGGUCACUGC 20 575

SCNNlA-1533 + GAGGGUGCAGAUGGUCACUGC 21 5382

SCNNlA-1534 + UGAGGGUGCAGAUGGUCACUGC 22 5383

SCNNlA-1535 + UUGAGGGUGCAGAUGGUCACUGC 23 5384

SCNNlA-1536 + AUUGAGGGUGCAGAUGGUCACUGC 24 5385

SCNNlA-1537 + UCCUCCGCCGUGGGCUGC 18 5386

SCNNlA-1538 + CUCCUCCGCCGUGGGCUGC 19 5387

1224

5535.1 SCNNlA-65 + CCUCCUCCGCCGUGGGCUGC 20 594

SCNNlA-1539 + UCCUCCUCCGCCGUGGGCUGC 21 5388

SCNNlA-1540 + CUCCUCCUCCGCCGUGGGCUGC 22 5389

SCNNlA-1541 + CCUCCUCCUCCGCCGUGGGCUGC 23 5390

SCNNlA-1542 + GCCUCCUCCUCCGCCGUGGGCUGC 24 5391

SCNNlA-1543 + GUCUUCAUGCGGUUGUGC 18 5392

SCNNlA-1544 + CGUCUUCAUGCGGUUGUGC 19 5393

SCNNlA-49 + CCGUCUUCAUGCGGUUGUGC 20 582

SCNNlA-1545 + GCCGUCUUCAUGCGGUUGUGC 21 5394

SCNNlA-1546 + GGCCGUCUUCAUGCGGUUGUGC 22 5395

SCNNlA-1547 + AGGCCGUCUUCAUGCGGUUGUGC 23 5396

SCNNlA-1548 + AAGGCCGUCUUCAUGCGGUUGUGC 24 5397

SCNNlA-1549 + UCCAGCUUGUUCCCCUUC 18 5398

SCNNlA-1550 + CUCCAGCUUGUUCCCCUUC 19 5399

SCNNlA-1551 + CCUCCAGCUUGUUCCCCUUC 20 5400

SCNNlA-1552 + UCCUCCAGCUUGUUCCCCUUC 21 5401

SCNNlA-1553 + CUCCUCCAGCUUGUUCCCCUUC 22 5402

SCNNlA-1554 + GCUCCUCCAGCUUGUUCCCCUUC 23 5403

SCNNlA-1555 + UGCUCCUCCAGCUUGUUCCCCUUC 24 5404

SCNNlA-1556 + UCACGCUUGUUCCCCUUC 18 5405

SCNNlA-1557 + CUCACGCUUGUUCCCCUUC 19 5406

SCNNlA-208 + CCUCACGCUUGUUCCCCUUC 20 835

SCNNlA-1558 + UCCUCACGCUUGUUCCCCUUC 21 5407

SCNNlA-1559 + CUCCUCACGCUUGUUCCCCUUC 22 5408

SCNNlA-1560 + GCUCCUCACGCUUGUUCCCCUUC 23 5409

SCNNlA-1561 + UGCUCCUCACGCUUGUUCCCCUUC 24 5410

SCNNlA-1562 + AUGGUCACUGCGGGGAAG 18 5411

SCNNlA-1563 + GAUGGUCACUGCGGGGAAG 19 5412

SCNNlA-238 + AGAUGGUCACUGCGGGGAAG 20 858

SCNNlA-1564 + CAGAUGGUCACUGCGGGGAAG 21 5413

SCNNlA-1565 + GCAGAUGGUCACUGCGGGGAAG 22 5414

SCNNlA-1566 + UGCAGAUGGUCACUGCGGGGAAG 23 5415

SCNNlA-1567 + GUGCAGAUGGUCACUGCGGGGAAG 24 5416

SCNNlA-1568 + AUGGUGGUGUUGUUGCAG 18 5417

SCNNlA-1569 + GAUGGUGGUGUUGUUGCAG 19 5418

SCNNlA-221 + GGAUGGUGGUGUUGUUGCAG 20 844

SCNNlA-1570 + UGGAUGGUGGUGUUGUUGCAG 21 5419

SCNNlA-1571 + GUGGAUGGUGGUGUUGUUGCAG 22 5420

SCNNlA-1572 + CGUGGAUGGUGGUGUUGUUGCAG 23 5421

SCNNlA-1573 + CCGUGGAUGGUGGUGUUGUUGCAG 24

5422

SCNNlA-1574 + AAGACGAGCUUGUCCGAG 18 5423

1225

5535.1 SCNNlA-1575 + GAAGACGAGCUUGUCCGAG 19 5424

SCNNlA-236 + GGAAGACGAGCUUGUCCGAG 20 856

SCNNlA-1576 + GGGAAGACGAGCUUGUCCGAG 21 5425

SCNNlA-1577 + GGGGAAGACGAGCUUGUCCGAG 22 5426

SCNNlA-1578 + CGGGGAAGACGAGCUUGUCCGAG 23 5427

SCNNlA-1579 + GCGGGGAAGACGAGCUUGUCCGAG 24 5428

SCNNlA-1580 + UUGAGGCUGACGGGGUAG 18 5429

SCNNlA-1581 + GUUGAGGCUGACGGGGUAG 19 5430

SCNNlA-232 + UGUUGAGGCUGACGGGGUAG 20 853

SCNNlA-1582 + AUGUUGAGGCUGACGGGGUAG 21 5431

SCNNlA-1583 + GAUGUUGAGGCUGACGGGGUAG 22 5432

SCNNlA-1584 + UGAUGUUGAGGCUGACGGGGUAG 23 5433

SCNNlA-1585 + UUGAUGUUGAGGCUGACGGGGUAG 24

5434

SCNNlA-1586 + GAGCUCUCGGUAGGAGCG 18 5435

SCNNlA-1587 + AGAGCUCUCGGUAGGAGCG 19 5436

SCNNlA-216 + AAGAGCUCUCGGUAGGAGCG 20 840

SCNNlA-1588 + GAAGAGCUCUCGGUAGGAGCG 21 5437

SCNNlA-1589 + CGAAGAGCUCUCGGUAGGAGCG 22 5438

SCNNlA-1590 + UCGAAGAGCUCUCGGUAGGAGCG 23 5439

SCNNlA-1591 + CUCGAAGAGCUCUCGGUAGGAGCG 24 5440

SCNNlA-1592 + GUGCAGAUGGUCACUGCG 18 5441

SCNNlA-1593 + GGUGCAGAUGGUCACUGCG 19 5442

SCNNlA-39 + GGGUGCAGAUGGUCACUGCG 20 518

SCNNlA-1594 + AGGGUGCAGAUGGUCACUGCG 21 5443

SCNNlA-1595 + GAGGGUGCAGAUGGUCACUGCG 22 5444

SCNNlA-1596 + UGAGGGUGCAGAUGGUCACUGCG 23 5445

SCNNlA-1597 + UUGAGGGUGCAGAUGGUCACUGCG 24 5446

SCNNlA-1598 + UUGUUGCAGAAGAACUCG 18 5447

SCNNlA-1599 + GUUGUUGCAGAAGAACUCG 19 5448

SCNNlA-219 + UGUUGUUGCAGAAGAACUCG 20 842

SCNNlA-1600 + GUGUUGUUGCAGAAGAACUCG 21 5449

SCNNlA-1601 + GGUGUUGUUGCAGAAGAACUCG 22 5450

SCNNlA-1602 + UGGUGUUGUUGCAGAAGAACUCG 23 5451

SCNNlA-1603 + GUGGUGUUGUUGCAGAAGAACUCG 24

5452

SCNNlA-1604 + CAAGGGUCAGGGUCAAGG 18 5453

SCNNlA-1605 + G C A AG GGUCAGGGUCAAGG 19 5454

SCNNlA-1606 + AGCAAGGGUCAGGGUCAAGG 20 5455

SCNNlA-1607 + GAGCAAGGGUCAGGGUCAAGG 21 5456

SCNNlA-1608 + AGAGCAAGGGUCAGGGUCAAGG 22 5457

SCNNlA-1609 + GAGAGCAAGGGUCAGGGUCAAGG 23 5458

1226

5535.1 SCNNlA-1610 + GGAGAGCAAGGGUCAGGGUCAAGG 24 5459

SCNNlA-1611 + AGCUCUCGGUAGGAGCGG 18 5460

SCNNlA-1612 + GAGCUCUCGGUAGGAGCGG 19 5461

SCNNlA-60 + AGAGCUCUCGGUAGGAGCGG 20 590

SCNNlA-1613 + AAGAGCUCUCGGUAGGAGCGG 21 5462

SCNNlA-1614 + GAAGAGCUCUCGGUAGGAGCGG 22 5463

SCNNlA-1615 + CGAAGAGCUCUCGGUAGGAGCGG 23 5464

SCNNlA-1616 + UCGAAGAGCUCUCGGUAGGAGCGG 24 5465

SCNNlA-1617 + AACUCGAAGAGCUCUCGG 18 5466

SCNNlA-1618 + GAACUCGAAGAGCUCUCGG 19 5467

SCNNlA-218 + AGAACUCGAAGAGCUCUCGG 20 841

SCNNlA-1619 + AAGAACUCGAAGAGCUCUCGG 21 5468

SCNNlA-1620 + GAAGAACUCGAAGAGCUCUCGG 22 5469

SCNNlA-1621 + AGAAGAACUCGAAGAGCUCUCGG 23 5470

SCNNlA-1622 + CAGAAGAACUCGAAGAGCUCUCGG 24 5471

SCNNlA-1623 + GCCCCGGAGUGGAUUGGG 18 5472

SCNNlA-1624 + AGCCCCGGAGUGGAUUGGG 19 5473

SCNNlA-1625 + GAGCCCCGGAGUGGAUUGGG 20 5474

SCNNlA-1626 + UGAGCCCCGGAGUGGAUUGGG 21 5475

SCNNlA-1627 + AUGAGCCCCGGAGUGGAUUGGG 22 5476

SCNNlA-1628 + CAUGAGCCCCGGAGUGGAUUGGG 23 5477

SCNNlA-1629 + UCAUGAGCCCCGGAGUGGAUUGGG 24 5478

SCNNlA-1630 + CAUGAUACCUCCCCUUGG 18 5479

SCNNlA-1631 + UCAUGAUACCUCCCCUUGG 19 5480

SCNNlA-1632 + CUCAUGAUACCUCCCCUUGG 20 5481

SCNNlA-1633 + GCUCAUGAUACCUCCCCUUGG 21 5482

SCNNlA-1634 + UGCUCAUGAUACCUCCCCUUGG 22 5483

SCNNlA-1635 + CUGCUCAUGAUACCUCCCCUUGG 23 5484

SCNNlA-1636 + ACUGCUCAUGAUACCUCCCCUUGG 24 5485

SCNNlA-1637 + UCCGAGUUGAGGUUGAUG 18 5486

SCNNlA-1638 + GUCCGAGUUGAGGUUGAUG 19 5487

SCNNlA-235 + UGUCCGAGUUGAGGUUGAUG 20 855

SCNNlA-1639 + UUGUCCGAGUUGAGGUUGAUG 21 5488

SCNNlA-1640 + CUUGUCCGAGUUGAGGUUGAUG 22 5489

SCNNlA-1641 + GCUUGUCCGAGUUGAGGUUGAUG 23 5490

SCNNlA-1642 + AGCUUGUCCGAGUUGAGGUUGAUG 24

5491

SCNNlA-1643 + GGGUGCAGAUGGUCACUG 18 5492

SCNNlA-1644 + AGGGUGCAGAUGGUCACUG 19 5493

SCNNlA-37 + GAGGGUGCAGAUGGUCACUG 20 517

SCNNlA-1645 + UGAGGGUGCAGAUGGUCACUG 21 5494

SCNNlA-1646 + UUGAGGGUGCAGAUGGUCACUG 22 5495

1227

5535.1 SCNNlA-1647 + AUUGAGGGUGCAGAUGGUCACUG 23 5496

SCNNlA-1648 + GAUUGAGGGUGCAGAUGGUCACUG 24

5497

SCNNlA-1649 + GAGCCCUGGAGUGGACUG 18 5498

SCNNlA-1650 + UGAGCCCUGGAGUGGACUG 19 5499

SCNNlA-74 + AUGAGCCCUGGAGUGGACUG 20 601

SCNNlA-1651 + CAUGAGCCCUGGAGUGGACUG 21 5500

SCNNlA-1652 + UCAUGAGCCCUGGAGUGGACUG 22 5501

SCNNlA-1653 + UUCAUGAGCCCUGGAGUGGACUG 23 5502

SCNNlA-1654 + CUUCAUGAGCCCUGGAGUGGACUG 24 5503

SCNNlA-1655 + GAGGGACUAACCGACCUG 18 5504

SCNNlA-1656 + AGAGGGACUAACCGACCUG 19 5505

SCNNlA-1657 + CAGAGGGACUAACCGACCUG 20 5506

SCNNlA-1658 + GCAGAGGGACUAACCGACCUG 21 5507

SCNNlA-1659 + GGCAGAGGGACUAACCGACCUG 22 5508

SCNNlA-1660 + GGGCAGAGGGACUAACCGACCUG 23 5509

SCNNlA-1661 + GGGGCAGAGGGACUAACCGACCUG 24 5510

SCNNlA-1662 + AGGUUGAUGUUGAGGCUG 18 5511

SCNNlA-1663 + GAGGUUGAUGUUGAGGCUG 19 5512

SCNNlA-234 + UGAGGUUGAUGUUGAGGCUG 20 854

SCNNlA-1664 + UUGAGGUUGAUGUUGAGGCUG 21 5513

SCNNlA-1665 + GUUGAGGUUGAUGUUGAGGCUG 22 5514

SCNNlA-1666 + AGUUGAGGUUGAUGUUGAGGCUG 23 5515

SCNNlA-1667 + GAGUUGAGGUUGAUGUUGAGGCUG 24

5516

SCNNlA-1668 + GAGACCUGGUAUGGGCUG 18 5517

SCNNlA-1669 + UGAGACCUGGUAUGGGCUG 19 5518

SCNNlA-1670 + AUGAGACCUGGUAUGGGCUG 20 5519

SCNNlA-1671 + CAUGAGACCUGGUAUGGGCUG 21 5520

SCNNlA-1672 + CCAUGAGACCUGGUAUGGGCUG 22 5521

SCNNlA-1673 + UCCAUGAGACCUGGUAUGGGCUG 23 5522

SCNNlA-1674 + CUCCAUGAGACCUGGUAUGGGCUG 24 5523

SCNNlA-1675 + CUCCUCCGCCGUGGGCUG 18 5524

SCNNlA-1676 + CCUCCUCCGCCGUGGGCUG 19 5525

SCNNlA-212 + UCCUCCUCCGCCGUGGGCUG 20 837

SCNNlA-1677 + CUCCUCCUCCGCCGUGGGCUG 21 5526

SCNNlA-1678 + CCUCCUCCUCCGCCGUGGGCUG 22 5527

SCNNlA-1679 + GCCUCCUCCUCCGCCGUGGGCUG 23 5528

SCNNlA-1680 + GGCCUCCUCCUCCGCCGUGGGCUG 24 5529

SCNNlA-1681 + UACAUCAUGCCAAAGGUG 18 5530

SCNNlA-1682 + GUACAUCAUGCCAAAGGUG 19 5531

SCNNlA-229 + AGUACAUCAUGCCAAAGGUG 20 850

1228

5535.1 SCNNlA-1683 + CAGUACAUCAUGCCAAAGGUG 21 5532

SCNNlA-1684 + CCAGUACAUCAUGCCAAAGGUG 22 5533

SCNNlA-1685 + GCCAGUACAUCAUGCCAAAGGUG 23 5534

SCNNlA-1686 + UGCCAGUACAUCAUGCCAAAGGUG 24 5535

SCNNlA-1687 + GCCCUGGAGUGGACUGUG 18 5536

SCNNlA-1688 + AGCCCUGGAGUGGACUGUG 19 5537

SCNNlA-202 + GAGCCCUGGAGUGGACUGUG 20 831

SCNNlA-1689 + UGAGCCCUGGAGUGGACUGUG 21 5538

SCNNlA-1690 + AUGAGCCCUGGAGUGGACUGUG 22 5539

SCNNlA-1691 + CAUGAGCCCUGGAGUGGACUGUG 23 5540

SCNNlA-1692 + UCAUGAGCCCUGGAGUGGACUGUG 24 5541

SCNNlA-1693 + CGUCUUCAUGCGGUUGUG 18 5542

SCNNlA-1694 + CCGUCUUCAUGCGGUUGUG 19 5543

SCNNlA-227 + GCCGUCUUCAUGCGGUUGUG 20 848

SCNNlA-1695 + GGCCGUCUUCAUGCGGUUGUG 21 5544

SCNNlA-1696 + AGGCCGUCUUCAUGCGGUUGUG 22 5545

SCNNlA-1697 + AAGGCCGUCUUCAUGCGGUUGUG 23 5546

SCNNlA-1698 + GAAGGCCGUCUUCAUGCGGUUGUG 24 5547

SCNNlA-1699 + GAGCCCCGGAGUGGAUUG 18 5548

SCNNlA-1700 + UGAGCCCCGGAGUGGAUUG 19 5549

SCNNlA-419 + AUGAGCCCCGGAGUGGAUUG 20 4268

SCNNlA-1701 + CAUGAGCCCCGGAGUGGAUUG 21 5550

SCNNlA-1702 + UCAUGAGCCCCGGAGUGGAUUG 22 5551

SCNNlA-1703 + UUCAUGAGCCCCGGAGUGGAUUG 23 5552

SCNNlA-1704 + CUUCAUGAGCCCCGGAGUGGAUUG 24 5553

SCNNlA-1705 + UGGAUGGUGGUGUUGUUG 18 5554

SCNNlA-1706 + GUGGAUGGUGGUGUUGUUG 19 5555

SCNNlA-222 + CGUGGAUGGUGGUGUUGUUG 20 845

SCNNlA-1707 + CCGUGGAUGGUGGUGUUGUUG 21 5556

SCNNlA-1708 + GCCGUGGAUGGUGGUGUUGUUG 22 5557

SCNNlA-1709 + CGCCGUGGAUGGUGGUGUUGUUG 23 5558

SCNNlA-1710 + GCGCCGUGGAUGGUGGUGUUGUUG 24

5559

SCNNlA-1711 + GGAGCGGUGGAACUCGAU 18 5560

SCNNlA-1712 + AGGAGCGGUGGAACUCGAU 19 5561

SCNNlA-214 + UAGGAGCGGUGGAACUCGAU 20 839

SCNNlA-1713 + GUAGGAGCGGUGGAACUCGAU 21 5562

SCNNlA-1714 + GGUAGGAGCGGUGGAACUCGAU 22 5563

SCNNlA-1715 + CGGUAGGAGCGGUGGAACUCGAU 23 5564

SCNNlA-1716 + UCGGUAGGAGCGGUGGAACUCGAU 24 5565

SCNNlA-1717 + AUGAGCCCCGGAGUGGAU 18 5566

SCNNlA-1718 + CAUGAGCCCCGGAGUGGAU 19 5567

1229

5535.1 SCNNlA-420 + UCAUGAGCCCCGGAGUGGAU 20 4269

SCNNlA-1719 + UUCAUGAGCCCCGGAGUGGAU 21 5568

SCNNlA-1720 + CUUCAUGAGCCCCGGAGUGGAU 22 5569

SCNNlA-1721 + CCUUCAUGAGCCCCGGAGUGGAU 23 5570

SCNNlA-1722 + CCCUUCAUGAGCCCCGGAGUGGAU 24 5571

SCNNlA-1723 + AGGGUGCAGAUGGUCACU 18 5572

SCNNlA-1724 + GAGGGUGCAGAUGGUCACU 19 5573

SCNNlA-242 + UGAGGGUGCAGAUGGUCACU 20 859

SCNNlA-1725 + UUGAGGGUGCAGAUGGUCACU 21 5574

SCNNlA-1726 + AUUGAGGGUGCAGAUGGUCACU 22 5575

SCNNlA-1727 + GAUUGAGGGUGCAGAUGGUCACU 23 5576

SCNNlA-1728 + GGAUUGAGGGUGCAGAUGGUCACU 24

5577

SCNNlA-1729 + UGAGCCCUGGAGUGGACU 18 5578

SCNNlA-1730 + AUGAGCCCUGGAGUGGACU 19 5579

SCNNlA-204 + CAUGAGCCCUGGAGUGGACU 20 832

SCNNlA-1731 + UCAUGAGCCCUGGAGUGGACU 21 5580

SCNNlA-1732 + UUCAUGAGCCCUGGAGUGGACU 22 5581

SCNNlA-1733 + CUUCAUGAGCCCUGGAGUGGACU 23 5582

SCNNlA-1734 + CCUUCAUGAGCCCUGGAGUGGACU 24 5583

SCNNlA-1735 + GCUCAUGAUACCUCCCCU 18 5584

SCNNlA-1736 + UGCUCAUGAUACCUCCCCU 19 5585

SCNNlA-457 + CUGCUCAUGAUACCUCCCCU 20 4306

SCNNlA-1737 + ACUGCUCAUGAUACCUCCCCU 21 5586

SCNNlA-1738 + UACUGCUCAUGAUACCUCCCCU 22 5587

SCNNlA-1739 + AUACUGCUCAUGAUACCUCCCCU 23 5588

SCNNlA-1740 + GAUACUGCUCAUGAUACCUCCCCU 24 5589

SCNNlA-1741 + CAGGGUCAAGGCUGAGCU 18 5590

SCNNlA-1742 + UCAGGGUCAAGGCUGAGCU 19 5591

SCNNlA-1743 + GUCAGGGUCAAGGCUGAGCU 20 5592

SCNNlA-1744 + GGUCAGGGUCAAGGCUGAGCU 21 5593

SCNNlA-1745 + GGGUCAGGGUCAAGGCUGAGCU 22 5594

SCNNlA-1746 + AGGGUCAGGGUCAAGGCUGAGCU 23 5595

SCNNlA-1747 + AAGGGUCAGGGUCAAGGCUGAGCU 24 5596

SCNNlA-1748 + UCUUCAUGCGGUUGUGCU 18 5597

SCNNlA-1749 + GUCUUCAUGCGGUUGUGCU 19 5598

SCNNlA-50 + CGUCUUCAUGCGGUUGUGCU 20 583

SCNNlA-1750 + CCGUCUUCAUGCGGUUGUGCU 21 5599

SCNNlA-1751 + GCCGUCUUCAUGCGGUUGUGCU 22 5600

SCNNlA-1752 + GGCCGUCUUCAUGCGGUUGUGCU 23 5601

SCNNlA-1753 + AGGCCGUCUUCAUGCGGUUGUGCU 24 5602

SCNNlA-1754 + GGGUAGCUGAAGUACUCU 18 5603

1230

5535.1 SCNNlA-1755 + GGGGUAGCUGAAGUACUCU 19 5604

SCNNlA-231 + CGGGGUAGCUGAAGUACUCU 20 852

SCNNlA-1756 + ACGGGGUAGCUGAAGUACUCU 21 5605

SCNNlA-1757 + GACGGGGUAGCUGAAGUACUCU 22 5606

SCNNlA-1758 + UGACGGGGUAGCUGAAGUACUCU 23 5607

SCNNlA-1759 + CUGACGGGGUAGCUGAAGUACUCU 24 5608

SCNNlA-1760 + UGCUGGGGCGCCGCAGGU 18 5609

SCNNlA-1761 + CUGCUGGGGCGCCGCAGGU 19 5610

SCNNlA-210 + GCUGCUGGGGCGCCGCAGGU 20 836

SCNNlA-1762 + GGCUGCUGGGGCGCCGCAGGU 21 5611

SCNNlA-1763 + GGGCUGCUGGGGCGCCGCAGGU 22 5612

SCNNlA-1764 + UGGGCUGCUGGGGCGCCGCAGGU 23 5613

SCNNlA-1765 + GUGGGCUGCUGGGGCGCCGCAGGU 24 5614

SCNNlA-1766 + ACUCGAAGAGCUCUCGGU 18 5615

SCNNlA-1767 + AACUCGAAGAGCUCUCGGU 19 5616

SCNNlA-58 + GAACUCGAAGAGCUCUCGGU 20 524

SCNNlA-1768 + AGAACUCGAAGAGCUCUCGGU 21 5617

SCNNlA-1769 + AAGAACUCGAAGAGCUCUCGGU 22 5618

SCNNlA-1770 + GAAGAACUCGAAGAGCUCUCGGU 23 5619

SCNNlA-1771 + AGAAGAACUCGAAGAGCUCUCGGU 24 5620

SCNNlA-1772 + CCCUCCAUGAGACCUGGU 18 5621

SCNNlA-1773 + CCCCUCCAUGAGACCUGGU 19 5622

SCNNlA-199 + UCCCCUCCAUGAGACCUGGU 20 828

SCNNlA-1774 + UUCCCCUCCAUGAGACCUGGU 21 5623

SCNNlA-1775 + GUUCCCCUCCAUGAGACCUGGU 22 5624

SCNNlA-1776 + UGUUCCCCUCCAUGAGACCUGGU 23 5625

SCNNlA-1777 + UUGUUCCCCUCCAUGAGACCUGGU 24 5626

SCNNlA-1778 + UGAGCCCCGGAGUGGAUU 18 5627

SCNNlA-1779 + AUGAGCCCCGGAGUGGAUU 19 5628

SCNNlA-425 + CAUGAGCCCCGGAGUGGAUU 20 4274

SCNNlA-1780 + UCAUGAGCCCCGGAGUGGAUU 21 5629

SCNNlA-1781 + UUCAUGAGCCCCGGAGUGGAUU 22 5630

SCNNlA-1782 + CUUCAUGAGCCCCGGAGUGGAUU 23 5631

SCNNlA-1783 + CCUUCAUGAGCCCCGGAGUGGAUU 24 5632

SCNNlA-1784 + GCUGGGGCGCCGCAGGUU 18 5633

SCNNlA-1785 + UGCUGGGGCGCCGCAGGUU 19 5634

SCNNlA-69 + CUGCUGGGGCGCCGCAGGUU 20 597

SCNNlA-1786 + GCUGCUGGGGCGCCGCAGGUU 21 5635

SCNNlA-1787 + GGCUGCUGGGGCGCCGCAGGUU 22 5636

SCNNlA-1788 + GGGCUGCUGGGGCGCCGCAGGUU 23 5637

SCNNlA-1789 + UGGGCUGCUGGGGCGCCGCAGGUU 24 5638

SCNNlA-1790 - C AG U A U C A AG G U A AG C A A 18 5639

1231

5535.1 SCNNlA-1791 - GCAGUAUCAAGGUAAGCAA 19 5640

SCNNlA-393 - AG C AG U A U C A AG G U A AG C A A 20 4242

SCNNlA-1792 - GAGCAGUAUCAAGGUAAGCAA 21 5641

SCNNlA-1793 - UGAGCAGUAU C A AG G U A AG C A A 22 5642

SCNNlA-1794 - AUGAGCAGUAUCAAGGUAAGCAA 23 5643

SCNNlA-1795 - CAUGAGCAGUAUCAAGGUAAGCAA 24 5644

SCNNlA-1796 - CACUCCAGGGCUCAUGAA 18 5645

SCNNlA-1797 - CCACUCCAGGGCUCAUGAA 19 5646

SCNNlA-11 - UCCACUCCAGGGCUCAUGAA 20 560

SCNNlA-1798 - GUCCACUCCAGGGCUCAUGAA 21 5647

SCNNlA-1799 - AGUCCACUCCAGGGCUCAUGAA 22 5648

SCNNlA-1800 - CAGUCCACUCCAGGGCUCAUGAA 23 5649

SCNNlA-1801 - ACAGUCCACUCCAGGGCUCAUGAA 24 5650

SCNNlA-1802 - CACUCCGGGGCUCAUGAA 18 5651

SCNNlA-1803 - CCACUCCGGGGCUCAUGAA 19 5652

SCNNlA-451 - UCCACUCCGGGGCUCAUGAA 20 4300

SCNNlA-1804 - AUCCACUCCGGGGCUCAUGAA 21 5653

SCNNlA-1805 - AAUCCACUCCGGGGCUCAUGAA 22 5654

SCNNlA-1806 - CAAUCCACUCCGGGGCUCAUGAA 23 5655

SCNNlA-1807 - CCAAUCCACUCCGGGGCUCAUGAA 24 5656

SCNNlA-1808 - G C AG U A U C A AG G U A AG C A 18 5657

SCNNlA-1809 - AGCAGUAUCAAGGUAAGCA 19 5658

SCNNlA-342 - GAGCAGUAUCAAGGUAAGCA 20 4191

SCNNlA-1810 - UGAGCAGUAUCAAGGUAAGCA 21 5659

SCNNlA-1811 - AUGAGCAGUAUCAAGGUAAGCA 22 5660

SCNNlA-1812 - CAUGAGCAGUAUCAAGGUAAGCA 23 5661

SCNNlA-1813 - UCAUGAGCAGUAUCAAGGUAAGCA 24 5662

SCNNlA-1814 - AGCCCAUACCAGGUCUCA 18 5663

SCNNlA-1815 - CAGCCCAUACCAGGUCUCA 19 5664

SCNNlA-1 - GCAGCCCAUACCAGGUCUCA 20 503

SCNNlA-1816 - UGCAGCCCAUACCAGGUCUCA 21 5665

SCNNlA-1817 - CUGCAGCCCAUACCAGGUCUCA 22 5666

SCNNlA-1818 - UCUGCAGCCCAUACCAGGUCUCA 23 5667

SCNNlA-1819 - CUCUGCAGCCCAUACCAGGUCUCA 24 5668

SCNNlA-1820 - GUUCCAGGGGUGAUGGGA 18 5669

SCNNlA-1821 - GGUUCCAGGGGUGAUGGGA 19 5670

SCNNlA-1822 - GGGUUCCAGGGGUGAUGGGA 20 5671

SCNNlA-1823 - CGGGUUCCAGGGGUGAUGGGA 21 5672

SCNNlA-1824 - UCGGGUUCCAGGGGUGAUGGGA 22 5673

SCNNlA-1825 - CUCGGGUUCCAGGGGUGAUGGGA 23 5674

SCNNlA-1826 - ACUCGGGUUCCAGGGGUGAUGGGA 24 5675

SCNNlA-1827 - CAUACCAGGUCUCAUGGA 18 5676

1232

5535.1 SCNNlA-1828 - CCAUACCAGGUCUCAUGGA 19 5677

SCNNlA-3 - CCCAUACCAGGUCUCAUGGA 20 556

SCNNlA-1829 - GCCCAUACCAGGUCUCAUGGA 21 5678

SCNNlA-1830 - AGCCCAUACCAGGUCUCAUGGA 22 5679

SCNNlA-1831 - CAGCCCAUACCAGGUCUCAUGGA 23 5680

SCNNlA-1832 - GCAGCCCAUACCAGGUCUCAUGGA 24 5681

SCNNlA-1833 - CCACUCCAGGGCUCAUGA 18 5682

SCNNlA-1834 - UCCACUCCAGGGCUCAUGA 19 5683

SCNNlA-10 - GUCCACUCCAGGGCUCAUGA 20 505

SCNNlA-1835 - AGUCCACUCCAGGGCUCAUGA 21 5684

SCNNlA-1836 - CAGUCCACUCCAGGGCUCAUGA 22 5685

SCNNlA-1837 - ACAGUCCACUCCAGGGCUCAUGA 23 5686

SCNNlA-1838 - CACAGUCCACUCCAGGGCUCAUGA 24 5687

SCNNlA-1839 - CCACUCCGGGGCUCAUGA 18 5688

SCNNlA-1840 - UCCACUCCGGGGCUCAUGA 19 5689

SCNNlA-400 - AUCCACUCCGGGGCUCAUGA 20 4249

SCNNlA-1841 - AAUCCACUCCGGGGCUCAUGA 21 5690

SCNNlA-1842 - CAAUCCACUCCGGGGCUCAUGA 22 5691

SCNNlA-1843 - CCAAUCCACUCCGGGGCUCAUGA 23 5692

SCNNlA-1844 - CCCAAUCCACUCCGGGGCUCAUGA 24 5693

SCNNlA-1845 - CUCGGGUUCCAGGGGUGA 18 5694

SCNNlA-1846 - ACUCGGGUUCCAGGGGUGA 19 5695

SCNNlA-401 - CACUCGGGUUCCAGGGGUGA 20 4250

SCNNlA-1847 - UCACUCGGGUUCCAGGGGUGA 21 5696

SCNNlA-1848 - CUCACUCGGGUUCCAGGGGUGA 22 5697

SCNNlA-1849 - CCUCACUCGGGUUCCAGGGGUGA 23 5698

SCNNlA-1850 - GCCUCACUCGGGUUCCAGGGGUGA 24 5699

SCNNlA-1851 - CGAGUUCCACCGCUCCUA 18 5700

SCNNlA-1852 - UCGAGUUCCACCGCUCCUA 19 5701

SCNNlA-190 - AUCGAGUUCCACCGCUCCUA 20 820

SCNNlA-1853 - GAUCGAGUUCCACCGCUCCUA 21 5702

SCNNlA-1854 - UGAUCGAGUUCCACCGCUCCUA 22 5703

SCNNlA-1855 - CUGAUCGAGUUCCACCGCUCCUA 23 5704

SCNNlA-1856 - CCUGAUCGAGUUCCACCGCUCCUA 24 5705

SCNNlA-1857 - CUCAACAUCAACCUCAAC 18 5706

SCNNlA-1858 - CCUCAACAUCAACCUCAAC 19 5707

SCNNlA-198 - GCCUCAACAUCAACCUCAAC 20 827

SCNNlA-1859 - AGCCUCAACAUCAACCUCAAC 21 5708

SCNNlA-1860 - CAG CC U CAAC AU C AACC U C AAC 22 5709

SCNNlA-1861 - UCAGCCUCAACAUCAACCUCAAC 23 5710

SCNNlA-1862 - GUCAGCCUCAACAUCAACCUCAAC 24 5711

SCNNlA-1863 - GUGGGCGCAGGGUGGGAC 18 5712

1233

5535.1 SCNNlA-1864 - UGUGGGCGCAGGGUGGGAC 19 5713

SCNNlA-1865 - AUGUGGGCGCAGGGUGGGAC 20 5714

SCNNlA-1866 - AAUGUGGGCGCAGGGUGGGAC 21 5715

SCNNlA-1867 - GAAUGUGGGCGCAGGGUGGGAC 22 5716

SCNNlA-1868 - AGAAUGUGGGCGCAGGGUGGGAC 23 5717

SCNNlA-1869 - GAGAAUGUGGGCGCAGGGUGGGAC 24

5718

SCNNlA-1870 - AGUUCCACCGCUCCUACC 18 5719

SCNNlA-1871 - GAGUUCCACCGCUCCUACC 19 5720

SCNNlA-191 - CGAGUUCCACCGCUCCUACC 20 821

SCNNlA-1872 - UCGAGUUCCACCGCUCCUACC 21 5721

SCNNlA-1873 - AUCGAGUUCCACCGCUCCUACC 22 5722

SCNNlA-1874 - GAUCGAGUUCCACCGCUCCUACC 23 5723

SCNNlA-1875 - UGAUCGAGUUCCACCGCUCCUACC 24 5724

SCNNlA-1876 - GAGAGGGCACUCAGGGCC 18 5725

SCNNlA-1877 - GGAGAGGGCACUCAGGGCC 19 5726

SCNNlA-1878 - GGGAGAGGGCACUCAGGGCC 20 5727

SCNNlA-1879 - UGGGAGAGGGCACUCAGGGCC 21 5728

SCNNlA-1880 - AUGGGAGAGGGCACUCAGGGCC 22 5729

SCNNlA-1881 - GAUGGGAGAGGGCACUCAGGGCC 23 5730

SCNNlA-1882 - UGAUGGGAGAGGGCACUCAGGGCC 24 5731

SCNNlA-1883 - AGGAGCAGGGGCUGGGCC 18 5732

SCNNlA-1884 - GAGGAGCAGGGGCUGGGCC 19 5733

SCNNlA-182 - UGAGGAGCAGGGGCUGGGCC 20 815

SCNNlA-1885 - GUGAGGAGCAGGGGCUGGGCC 21 5734

SCNNlA-1886 - CGUGAGGAGCAGGGGCUGGGCC 22 5735

SCNNlA-1887 - GCGUGAGGAGCAGGGGCUGGGCC 23 5736

SCNNlA-1888 - AGCGUGAGGAGCAGGGGCUGGGCC 24 5737

SCNNlA-1889 - UGGGACAUGGGCAUGGCC 18 5738

SCNNlA-1890 - GUGGGACAUGGGCAUGGCC 19 5739

SCNNlA-347 - GGUGGGACAUGGGCAUGGCC 20 4196

SCNNlA-1891 - GGGUGGGACAUGGGCAUGGCC 21 5740

SCNNlA-1892 - AGGGUGGGACAUGGGCAUGGCC 22 5741

SCNNlA-1893 - CAGGGUGGGACAUGGGCAUGGCC 23 5742

SCNNlA-1894 - GCAGGGUGGGACAUGGGCAUGGCC 24 5743

SCNNlA-1895 - UCAUGAAGGGGAACAAGC 18 5744

SCNNlA-1896 - CUCAUGAAGGGGAACAAGC 19 5745

SCNNlA-176 - GCUCAUGAAGGGGAACAAGC 20 811

SCNNlA-1897 - GGCUCAUGAAGGGGAACAAGC 21 5746

SCNNlA-1898 - GGGCUCAUGAAGGGGAACAAGC 22 5747

SCNNlA-1899 - AGGGCUCAUGAAGGGGAACAAGC 23 5748

SCNNlA-1900 - CAGGGCUCAUGAAGGGGAACAAGC 24 5749

1234

5535.1 SCNNlA-1901 - GGGGCUCAUGAAGGGGAACAAGC 23 5750

SCNNlA-1902 - CGGGGCUCAUGAAGGGGAACAAGC 24 5751

SCNNlA-1903 - UCAUGGAGGGGAACAAGC 18 5752

SCNNlA-1904 - CUCAUGGAGGGGAACAAGC 19 5753

SCNNlA-5 - UCUCAUGGAGGGGAACAAGC 20 557

SCNNlA-1905 - GUCUCAUGGAGGGGAACAAGC 21 5754

SCNNlA-1906 - GGUCUCAUGGAGGGGAACAAGC 22 5755

SCNNlA-1907 - AGGUCUCAUGGAGGGGAACAAGC 23 5756

SCNNlA-1908 - CAGGUCUCAUGGAGGGGAACAAGC 24 5757

SCNNlA-1909 - AG C AG U A U C A AG G U A AG C 18 5758

SCNNlA-1910 - GAGCAGUAUCAAGGUAAGC 19 5759

SCNNlA-1911 - UGAGCAGUAU C A AG G U A AG C 20 5760

SCNNlA-1912 - AUGAGCAGUAUCAAGGUAAGC 21 5761

SCNNlA-1913 - CAUGAGCAGUAUCAAGGUAAGC 22 5762

SCNNlA-1914 - UCAUGAGCAGUAUCAAGGUAAGC 23 5763

SCNNlA-1915 - AUCAUGAGCAGUAUCAAGGUAAGC 24 5764

SCNNlA-1916 - GGAACAAGCGUGAGGAGC 18 5765

SCNNlA-1917 - GGGAACAAGCGUGAGGAGC 19 5766

SCNNlA-14 - GGGGAACAAGCGUGAGGAGC 20 506

SCNNlA-1918 - AGGGGAACAAGCGUGAGGAGC 21 5767

SCNNlA-1919 - AAGGGGAACAAGCGUGAGGAGC 22 5768

SCNNlA-1920 - GAAGGGGAACAAGCGUGAGGAGC 23 5769

SCNNlA-1921 - UGAAGGGGAACAAGCGUGAGGAGC 24 5770

SCNNlA-1922 - UGCUCCCAGCACAACCGC 18 5771

SCNNlA-1923 - GUGCUCCCAGCACAACCGC 19 5772

SCNNlA-193 - UGUGCUCCCAGCACAACCGC 20 823

SCNNlA-1924 - GUGUGCUCCCAGCACAACCGC 21 5773

SCNNlA-1925 - GGUGUGCUCCCAGCACAACCGC 22 5774

SCNNlA-1926 - UGGUGUGCUCCCAGCACAACCGC 23 5775

SCNNlA-1927 - CUGGUGUGCUCCCAGCACAACCGC 24 5776

SCNNlA-1928 - GUGGGACAUGGGCAUGGC 18 5777

SCNNlA-1929 - GGUGGGACAUGGGCAUGGC 19 5778

SCNNlA-1930 - GGGUGGGACAUGGGCAUGGC 20 5779

SCNNlA-1931 - AGGGUGGGACAUGGGCAUGGC 21 5780

SCNNlA-1932 - CAGGGUGGGACAUGGGCAUGGC 22 5781

SCNNlA-1933 - GCAGGGUGGGACAUGGGCAUGGC 23 5782

SCNNlA-1934 - CGCAGGGUGGGACAUGGGCAUGGC 24 5783

SCNNlA-1935 - CUUCCAAGGGGAGGUAUC 18 5784

SCNNlA-1936 - CCUUCCAAGGGGAGGUAUC 19 5785

SCNNlA-1937 - CCCUUCCAAGGGGAGGUAUC 20 5786

SCNNlA-1938 - UCCCUUCCAAGGGGAGGUAUC 21 5787

SCNNlA-1939 - GUCCCUUCCAAGGGGAGGUAUC 22 5788

1235

5535.1 SCNNlA-1940 - UGUCCCUUCCAAGGGGAGGUAUC 23 5789

SCNNlA-1941 - CUGUCCCUUCCAAGGGGAGGUAUC 24 5790

SCNNlA-1942 - GCUCUCCCCAAUCCACUC 18 5791

SCNNlA-1943 - UGCUCUCCCCAAUCCACUC 19 5792

SCNNlA-410 - UUGCUCUCCCCAAUCCACUC 20 4259

SCNNlA-1944 - CUUGCUCUCCCCAAUCCACUC 21 5793

SCNNlA-1945 - CCUUGCUCUCCCCAAUCCACUC 22 5794

SCNNlA-1946 - CCCUUGCUCUCCCCAAUCCACUC 23 5795

SCNNlA-1947 - ACCCUUGCUCUCCCCAAUCCACUC 24 5796

SCNNlA-1948 - GCCCUCCACAGUCCACUC 18 5797

SCNNlA-1949 - AGCCCUCCACAGUCCACUC 19 5798

SCNNlA-170 - UAGCCCUCCACAGUCCACUC 20 808

SCNNlA-1950 - CUAGCCCUCCACAGUCCACUC 21 5799

SCNNlA-1951 - UCUAGCCCUCCACAGUCCACUC 22 5800

SCNNlA-1952 - CUCUAGCCCUCCACAGUCCACUC 23 5801

SCNNlA-1953 - ACUCUAGCCCUCCACAGUCCACUC 24 5802

SCNNlA-1954 - CAGUCCACUCCAGGGCUC 18 5803

SCNNlA-1955 - ACAGUCCACUCCAGGGCUC 19 5804

SCNNlA-171 - CACAGUCCACUCCAGGGCUC 20 809

SCNNlA-1956 - CCACAGUCCACUCCAGGGCUC 21 5805

SCNNlA-1957 - UCCACAGUCCACUCCAGGGCUC 22 5806

SCNNlA-1958 - CUCCACAGUCCACUCCAGGGCUC 23 5807

SCNNlA-1959 - CCUCCACAGUCCACUCCAGGGCUC 24 5808

SCNNlA-1960 - CAAUCCACUCCGGGGCUC 18 5809

SCNNlA-1961 - CCAAUCCACUCCGGGGCUC 19 5810

SCNNlA-1962 - CCCAAUCCACUCCGGGGCUC 20 5811

SCNNlA-1963 - CCCCAAUCCACUCCGGGGCUC 21 5812

SCNNlA-1964 - UCCCCAAUCCACUCCGGGGCUC 22 5813

SCNNlA-1965 - CUCCCCAAUCCACUCCGGGGCUC 23 5814

SCNNlA-1966 - UCUCCCCAAUCCACUCCGGGGCUC 24 5815

SCNNlA-1967 - CAGCCCAUACCAGGUCUC 18 5816

SCNNlA-1968 - GCAGCCCAUACCAGGUCUC 19 5817

SCNNlA-159 - UGCAGCCCAUACCAGGUCUC 20 803

SCNNlA-1969 - CUGCAGCCCAUACCAGGUCUC 21 5818

SCNNlA-1970 - UCUGCAGCCCAUACCAGGUCUC 22 5819

SCNNlA-1971 - CUCUGCAGCCCAUACCAGGUCUC 23 5820

SCNNlA-1972 - CCUCUGCAGCCCAUACCAGGUCUC 24 5821

SCNNlA-1973 - GCAGCCUCACUCGGGUUC 18 5822

SCNNlA-1974 - GGCAGCCUCACUCGGGUUC 19 5823

SCNNlA-1975 - GGGCAGCCUCACUCGGGUUC 20 5824

SCNNlA-1976 - GGGGCAGCCUCACUCGGGUUC 21 5825

SCNNlA-1977 - AGGGGCAGCCUCACUCGGGUUC 22 5826

1236

5535.1 SCNNlA-1978 - CAGGGGCAGCCUCACUCGGGUUC 23 5827

SCNNlA-1979 - CCAGGGGCAGCCUCACUCGGGUUC 24 5828

SCNNlA-1980 - CUCAUGAAGGGGAACAAG 18 5829

SCNNlA-1981 - GCUCAUGAAGGGGAACAAG 19 5830

SCNNlA-1982 - GGCUCAUGAAGGGGAACAAG 20 5831

SCNNlA-1983 - GGGCUCAUGAAGGGGAACAAG 21 5832

SCNNlA-1984 - GGGGCUCAUGAAGGGGAACAAG 22 5833

SCNNlA-1985 - CGGGGCUCAUGAAGGGGAACAAG 23 5834

SCNNlA-1986 - CCGGGGCUCAUGAAGGGGAACAAG 24 5835

SCNNlA-1987 - CUCAUGGAGGGGAACAAG 18 5836

SCNNlA-1988 - UCUCAUGGAGGGGAACAAG 19 5837

SCNNlA-165 - GUCUCAUGGAGGGGAACAAG 20 805

SCNNlA-1989 - GGUCUCAUGGAGGGGAACAAG 21 5838

SCNNlA-1990 - AGGUCUCAUGGAGGGGAACAAG 22 5839

SCNNlA-1991 - CAGGUCUCAUGGAGGGGAACAAG 23 5840

SCNNlA-1992 - CCAGGUCUCAUGGAGGGGAACAAG 24 5841

SCNNlA-1993 - CCAGCUGUCCCUUCCAAG 18 5842

SCNNlA-1994 - UCCAGCUGUCCCUUCCAAG 19 5843

SCNNlA-412 - AUCCAGCUGUCCCUUCCAAG 20 4261

SCNNlA-1995 - ACUCCAGGGCUCAUGAAG 18 5844

SCNNlA-1996 - CACUCCAGGGCUCAUGAAG 19 5845

SCNNlA-12 - CCACUCCAGGGCUCAUGAAG 20 561

SCNNlA-1997 - UCCACUCCAGGGCUCAUGAAG 21 5846

SCNNlA-1998 - GUCCACUCCAGGGCUCAUGAAG 22 5847

SCNNlA-1999 - AGUCCACUCCAGGGCUCAUGAAG 23 5848

SCNNlA-2000 - CAGUCCACUCCAGGGCUCAUGAAG 24 5849

SCNNlA-2001 - ACUCCGGGGCUCAUGAAG 18 5850

SCNNlA-2002 - CACUCCGGGGCUCAUGAAG 19 5851

SCNNlA-453 - CCACUCCGGGGCUCAUGAAG 20 4302

SCNNlA-2003 - UCCACUCCGGGGCUCAUGAAG 21 5852

SCNNlA-2004 - AUCCACUCCGGGGCUCAUGAAG 22 5853

SCNNlA-2005 - AAUCCACUCCGGGGCUCAUGAAG 23 5854

SCNNlA-2006 - CAAUCCACUCCGGGGCUCAUGAAG 24 5855

SCNNlA-2007 - GGGAACAAGCUGGAGGAG 18 5856

SCNNlA-2008 - GGGGAACAAGCUGGAGGAG 19 5857

SCNNlA-169 - AGGGGAACAAGCUGGAGGAG 20 807

SCNNlA-2009 - AAGGGGAACAAGCUGGAGGAG 21 5858

SCNNlA-2010 - GAAGGGGAACAAGCUGGAGGAG 22 5859

SCNNlA-2011 - UGAAGGGGAACAAGCUGGAGGAG 23 5860

SCNNlA-2012 - AUGAAGGGGAACAAGCUGGAGGAG 24 5861

SCNNlA-2013 - GAGGGGAACAAGCUGGAGGAG 21 5862

SCNNlA-2014 - GGAGGGGAACAAGCUGGAGGAG 22 5863

1237

5535.1 SCNNlA-2015 - UGGAGGGGAACAAGCUGGAGGAG 23 5864

SCNNlA-2016 - AUGGAGGGGAACAAGCUGGAGGAG 24 5865

SCNNlA-2017 - GGGAACAAGCGUGAGGAG 18 5866

SCNNlA-2018 - GGGGAACAAGCGUGAGGAG 19 5867

SCNNlA-179 - AGGGGAACAAGCGUGAGGAG 20 813

SCNNlA-2019 - AAGGGGAACAAGCGUGAGGAG 21 5868

SCNNlA-2020 - GAAGGGGAACAAGCGUGAGGAG 22 5869

SCNNlA-2021 - UGAAGGGGAACAAGCGUGAGGAG 23 5870

SCNNlA-2022 - AUGAAGGGGAACAAGCGUGAGGAG 24 5871

SCNNlA-2023 - CAGCAGCCCACGGCGGAG 18 5872

SCNNlA-2024 - CCAGCAGCCCACGGCGGAG 19 5873

SCNNlA-187 - CCCAGCAGCCCACGGCGGAG 20 818

SCNNlA-2025 - CCCCAGCAGCCCACGGCGGAG 21 5874

SCNNlA-2026 - GCCCCAGCAGCCCACGGCGGAG 22 5875

SCNNlA-2027 - CGCCCCAGCAGCCCACGGCGGAG 23 5876

SCNNlA-2028 - GCGCCCCAGCAGCCCACGGCGGAG 24 5877

SCNNlA-2029 - AUACCAGGUCUCAUGGAG 18 5878

SCNNlA-2030 - CAUACCAGGUCUCAUGGAG 19 5879

SCNNlA-4 - CCAUACCAGGUCUCAUGGAG 20 498

SCNNlA-2031 - CCCAUACCAGGUCUCAUGGAG 21 5880

SCNNlA-2032 - GCCCAUACCAGGUCUCAUGGAG 22 5881

SCNNlA-2033 - AGCCCAUACCAGGUCUCAUGGAG 23 5882

SCNNlA-2034 - CAGCCCAUACCAGGUCUCAUGGAG 24 5883

SCNNlA-2035 - GCGCCCCAGCAGCCCACG 18 5884

SCNNlA-2036 - GGCGCCCCAGCAGCCCACG 19 5885

SCNNlA-183 - CGGCGCCCCAGCAGCCCACG 20 816

SCNNlA-2037 - GCGGCGCCCCAGCAGCCCACG 21 5886

SCNNlA-2038 - UGCGGCGCCCCAGCAGCCCACG 22 5887

SCNNlA-2039 - CUGCGGCGCCCCAGCAGCCCACG 23 5888

SCNNlA-2040 - CCUGCGGCGCCCCAGCAGCCCACG 24 5889

SCNNlA-2041 - CCCCAGCAGCCCACGGCG 18 5890

SCNNlA-2042 - GCCCCAGCAGCCCACGGCG 19 5891

SCNNlA-185 - CGCCCCAGCAGCCCACGGCG 20 817

SCNNlA-2043 - GCGCCCCAGCAGCCCACGGCG 21 5892

SCNNlA-2044 - GGCGCCCCAGCAGCCCACGGCG 22 5893

SCNNlA-2045 - CGGCGCCCCAGCAGCCCACGGCG 23 5894

SCNNlA-2046 - GCGGCGCCCCAGCAGCCCACGGCG 24 5895

SCNNlA-2047 - GGAGAAUGUGGGCGCAGG 18 5896

SCNNlA-2048 - GGGAGAAUGUGGGCGCAGG 19 5897

SCNNlA-2049 - UGGGAGAAUGUGGGCGCAGG 20 5898

SCNNlA-2050 - AGCAGCCCACGGCGGAGG 18 5899

SCNNlA-2051 - CAGCAGCCCACGGCGGAGG 19 5900

1238

5535.1 SCNNlA-23 - CCAGCAGCCCACGGCGGAGG 20 566

SCNNlA-2052 - CCCAGCAGCCCACGGCGGAGG 21 5901

SCNNlA-2053 - CCCCAGCAGCCCACGGCGGAGG 22 5902

SCNNlA-2054 - GCCCCAGCAGCCCACGGCGGAGG 23 5903

SCNNlA-2055 - CGCCCCAGCAGCCCACGGCGGAGG 24 5904

SCNNlA-2056 - CGCCCCAGCAGCCCACGG 18 5905

SCNNlA-2057 - GCGCCCCAGCAGCCCACGG 19 5906

SCNNlA-21 - GGCGCCCCAGCAGCCCACGG 20 510

SCNNlA-2058 - CGGCGCCCCAGCAGCCCACGG 21 5907

SCNNlA-2059 - GCGGCGCCCCAGCAGCCCACGG 22 5908

SCNNlA-2060 - UGCGGCGCCCCAGCAGCCCACGG 23 5909

SCNNlA-2061 - CUGCGGCGCCCCAGCAGCCCACGG 24 5910

SCNNlA-2062 - CCCAGCAGCCCACGGCGG 18 5911

SCNNlA-2063 - CCCCAGCAGCCCACGGCGG 19 5912

SCNNlA-22 - GCCCCAGCAGCCCACGGCGG 20 511

SCNNlA-2064 - CGCCCCAGCAGCCCACGGCGG 21 5913

SCNNlA-2065 - GCGCCCCAGCAGCCCACGGCGG 22 5914

SCNNlA-2066 - GGCGCCCCAGCAGCCCACGGCGG 23 5915

SCNNlA-2067 - CGGCGCCCCAGCAGCCCACGGCGG 24 5916

SCNNlA-2068 - GAGAAUGUGGGCGCAGGG 18 5917

SCNNlA-2069 - GGAGAAUGUGGGCGCAGGG 19 5918

SCNNlA-354 - GGGAGAAUGUGGGCGCAGGG 20 4203

SCNNlA-2070 - UGGGAGAAUGUGGGCGCAGGG 21 5919

SCNNlA-2071 - GUGGGAGAAUGUGGGCGCAGGG 22 5920

SCNNlA-2072 - AGUGGGAGAAUGUGGGCGCAGGG 23 5921

SCNNlA-2073 - GAGUGGGAGAAUGUGGGCGCAGGG 24

5922

SCNNlA-2074 - AAGCGUGAGGAGCAGGGG 18 5923

SCNNlA-2075 - CAAG CG U G AG G AG CAG G GG 19 5924

SCNNlA-181 - ACAAGCGUGAGGAGCAGGGG 20 814

SCNNlA-2076 - AACAAGCGUGAGGAGCAGGGG 21 5925

SCNNlA-2077 - GAACAAGCGUGAGGAGCAGGGG 22 5926

SCNNlA-2078 - GGAACAAGCGUGAGGAGCAGGGG 23 5927

SCNNlA-2079 - GGGAACAAGCGUGAGGAGCAGGGG 24 5928

SCNNlA-2080 - CCAUACCAGGUCUCAUGG 18 5929

SCNNlA-2081 - CCCAUACCAGGUCUCAUGG 19 5930

SCNNlA-2 - GCCCAUACCAGGUCUCAUGG 20 497

SCNNlA-2082 - AGCCCAUACCAGGUCUCAUGG 21 5931

SCNNlA-2083 - CAGCCCAUACCAGGUCUCAUGG 22 5932

SCNNlA-2084 - GCAGCCCAUACCAGGUCUCAUGG 23 5933

SCNNlA-2085 - UGCAGCCCAUACCAGGUCUCAUGG 24 5934

SCNNlA-2086 - GGGUUCCAGGGGUGAUGG 18 5935

1239

5535.1 SCNNlA-2087 - CGGGUUCCAGGGGUGAUGG 19 5936

SCNNlA-2088 - UCGGGUUCCAGGGGUGAUGG 20 5937

SCNNlA-2089 - CUCGGGUUCCAGGGGUGAUGG 21 5938

SCNNlA-2090 - ACUCGGGUUCCAGGGGUGAUGG 22 5939

SCNNlA-2091 - CACUCGGGUUCCAGGGGUGAUGG 23 5940

SCNNlA-2092 - UCACUCGGGUUCCAGGGGUGAUGG 24 5941

SCNNlA-2093 - U G AAG GG G AAC AAG C U G G 18 5942

SCNNlA-2094 - AUGAAGGGGAACAAGCUGG 19 5943

SCNNlA-455 - CAUGAAGGGGAACAAGCUGG 20 4304

SCNNlA-2095 - UCAUGAAGGGGAACAAGCUGG 21 5944

SCNNlA-2096 - CUCAUGAAGGGGAACAAGCUGG 22 5945

SCNNlA-2097 - GCUCAUGAAGGGGAACAAGCUGG 23 5946

SCNNlA-2098 - GGCUCAUGAAGGGGAACAAGCUGG 24 5947

SCNNlA-2099 - UGGAGGGGAACAAGCUGG 18 5948

SCNNlA-2100 - AUGGAGGGGAACAAGCUGG 19 5949

SCNNlA-6 - CAUGGAGGGGAACAAGCUGG 20 558

SCNNlA-2101 - UCAUGGAGGGGAACAAGCUGG 21 5950

SCNNlA-2102 - CUCAUGGAGGGGAACAAGCUGG 22 5951

SCNNlA-2103 - UCUCAUGGAGGGGAACAAGCUGG 23 5952

SCNNlA-2104 - GUCUCAUGGAGGGGAACAAGCUGG 24 5953

SCNNlA-2105 - UCCACUCCAGGGCUCAUG 18 5954

SCNNlA-2106 - GUCCACUCCAGGGCUCAUG 19 5955

SCNNlA-172 - AGUCCACUCCAGGGCUCAUG 20 810

SCNNlA-2107 - CAGUCCACUCCAGGGCUCAUG 21 5956

SCNNlA-2108 - ACAGUCCACUCCAGGGCUCAUG 22 5957

SCNNlA-2109 - CACAGUCCACUCCAGGGCUCAUG 23 5958

SCNNlA-2110 - CCA CAGUCCACUCCAGGGCUCAUG 24 5959

SCNNlA-2111 - UCCACUCCGGGGCUCAUG 18 5960

SCNNlA-2112 - AUCCACUCCGGGGCUCAUG 19 5961

SCNNlA-2113 - AAUCCACUCCGGGGCUCAUG 20 5962

SCNNlA-2114 - CAAUCCACUCCGGGGCUCAUG 21 5963

SCNNlA-2115 - CCAAUCCACUCCGGGGCUCAUG 22 5964

SCNNlA-2116 - CCCAAUCCACUCCGGGGCUCAUG 23 5965

SCNNlA-2117 - CCCCAAUCCACUCCGGGGCUCAUG 24 5966

SCNNlA-2118 - CCCAUACCAGGUCUCAUG 18 5967

SCNNlA-2119 - GCCCAUACCAGGUCUCAUG 19 5968

SCNNlA-161 - AGCCCAUACCAGGUCUCAUG 20 804

SCNNlA-2120 - CAGCCCAUACCAGGUCUCAUG 21 5969

SCNNlA-2121 - GCAGCCCAUACCAGGUCUCAUG 22 5970

SCNNlA-2122 - UGCAGCCCAUACCAGGUCUCAUG 23 5971

SCNNlA-2123 - CUGCAGCCCAUACCAGGUCUCAUG 24 5972

SCNNlA-2124 - AUGAAGGGGAACAAGCUG 18 5973

1240

5535.1 SCNNlA-2125 - CAUGAAGGGGAACAAGCUG 19 5974

SCNNlA-2126 - UCAUGAAGGGGAACAAGCUG 20 5975

SCNNlA-2127 - CUCAUGAAGGGGAACAAGCUG 21 5976

SCNNlA-2128 - GCUCAUGAAGGGGAACAAGCUG 22 5977

SCNNlA-2129 - GGCUCAUGAAGGGGAACAAGCUG 23 5978

SCNNlA-2130 - GGGCUCAUGAAGGGGAACAAGCUG 24 5979

SCNNlA-2131 - AUGGAGGGGAACAAGCUG 18 5980

SCNNlA-2132 - CAUGGAGGGGAACAAGCUG 19 5981

SCNNlA-167 - UCAUGGAGGGGAACAAGCUG 20 806

SCNNlA-2133 - CUCAUGGAGGGGAACAAGCUG 21 5982

SCNNlA-2134 - UCUCAUGGAGGGGAACAAGCUG 22 5983

SCNNlA-2135 - GUCUCAUGGAGGGGAACAAGCUG 23 5984

SCNNlA-2136 - GGUCUCAUGGAGGGGAACAAGCUG 24 5985

SCNNlA-2137 - UGAAGGGGAACAAGCGUG 18 5986

SCNNlA-2138 - AUGAAGGGGAACAAGCGUG 19 5987

SCNNlA-13 - CA U G AAG GG G AAC AAG CG U G 20 562

SCNNlA-2139 - UCAUGAAGGGGAACAAGCGUG 21 5988

SCNNlA-2140 - CUCAUGAAGGGGAACAAGCGUG 22 5989

SCNNlA-2141 - GCUCAUGAAGGGGAACAAGCGUG 23 5990

SCNNlA-2142 - GGCUCAUGAAGGGGAACAAGCGUG 24 5991

SCNNlA-2143 - ACUCGGGUUCCAGGGGUG 18 5992

SCNNlA-2144 - CACUCGGGUUCCAGGGGUG 19 5993

SCNNlA-2145 - UCACUCGGGUUCCAGGGGUG 20 5994

SCNNlA-2146 - CUCACUCGGGUUCCAGGGGUG 21 5995

SCNNlA-2147 - CCUCACUCGGGUUCCAGGGGUG 22 5996

SCNNlA-2148 - GCCUCACUCGGGUUCCAGGGGUG 23 5997

SCNNlA-2149 - AGCCUCACUCGGGUUCCAGGGGUG 24 5998

SCNNlA-2150 - UCGGGUUCCAGGGGUGAU 18 5999

SCNNlA-2151 - CUCGGGUUCCAGGGGUGAU 19 6000

SCNNlA-421 - ACUCGGGUUCCAGGGGUGAU 20 4270

SCNNlA-2152 - CACUCGGGUUCCAGGGGUGAU 21 6001

SCNNlA-2153 - UCACUCGGGUUCCAGGGGUGAU 22 6002

SCNNlA-2154 - CUCACUCGGGUUCCAGGGGUGAU 23 6003

SCNNlA-2155 - CCUCACUCGGGUUCCAGGGGUGAU 24 6004

SCNNlA-2156 - UGCUCUCCCCAAUCCACU 18 6005

SCNNlA-2157 - UUGCUCUCCCCAAUCCACU 19 6006

SCNNlA-2158 - CUUGCUCUCCCCAAUCCACU 20 6007

SCNNlA-2159 - CCUUGCUCUCCCCAAUCCACU 21 6008

SCNNlA-2160 - CCCUUGCUCUCCCCAAUCCACU 22 6009

SCNNlA-2161 - ACCCUUGCUCUCCCCAAUCCACU 23 6010

SCNNlA-2162 - GACCCUUGCUCUCCCCAAUCCACU 24 6011

SCNNlA-2163 - GUGAUGGGAGAGGGCACU 18 6012

1241

5535.1 SCNNlA-2164 - GGUGAUGGGAGAGGGCACU 19 6013

SCNNlA-2165 - GGGUGAUGGGAGAGGGCACU 20 6014

SCNNlA-2166 - GGGGUGAUGGGAGAGGGCACU 21 6015

SCNNlA-2167 - AGGGGUGAUGGGAGAGGGCACU 22 6016

SCNNlA-2168 - CAGGGGUGAUGGGAGAGGGCACU 23 6017

SCNNlA-2169 - CCAGGGGUGAUGGGAGAGGGCACU 24 6018

SCNNlA-2170 - AUGAAGGGG A AC A AG CG U 18 6019

SCNNlA-2171 - CAUGAAGGGGAACAAGCGU 19 6020

SCNNlA-177 - UCAUGAAGGGGAACAAGCGU 20 812

SCNNlA-2172 - CUCAUGAAGGGGAACAAGCGU 21 6021

SCNNlA-2173 - GCUCAUGAAGGGGAACAAGCGU 22 6022

SCNNlA-2174 - GGCUCAUGAAGGGGAACAAGCGU 23 6023

SCNNlA-2175 - GGGCUCAUGAAGGGGAACAAGCGU 24 6024

SCNNlA-2176 - UAAGCAAGGGAACCUGGU 18 6025

SCNNlA-2177 - GUAAGCAAGGGAACCUGGU 19 6026

SCNNlA-2178 - GGUAAGCAAGGGAACCUGGU 20 6027

SCNNlA-2179 - AGGUAAGCAAGGGAACCUGGU 21 6028

SCNNlA-2180 - AAGGUAAGCAAGGGAACCUGGU 22 6029

SCNNlA-2181 - CAAGGUAAGCAAGGGAACCUGGU 23 6030

SCNNlA-2182 - UCAAGGUAAGCAAGGGAACCUGGU 24 6031

SCNNlA-2183 - CCGCAUGAAGACGGCCUU 18 6032

SCNNlA-2184 - ACCGCAUGAAGACGGCCUU 19 6033

SCNNlA-194 - AACCGCAUGAAGACGGCCUU 20 824

SCNNlA-2185 - CAACCGCAUGAAGACGGCCUU 21 6034

SCNNlA-2186 - ACAACCGCAUGAAGACGGCCUU 22 6035

SCNNlA-2187 - CACAACCGCAUGAAGACGGCCUU 23 6036

SCNNlA-2188 - GCACAACCGCAUGAAGACGGCCUU 24 6037

SCNNlA-2189 - GGCAAUUCGGCCUGCUUU 18 6038

SCNNlA-2190 - UGGCAAUUCGGCCUGCUUU 19 6039

SCNNlA-195 - CUGGCAAUUCGGCCUGCUUU 20 825

SCNNlA-2191 - ACUGGCAAUUCGGCCUGCUUU 21 6040

SCNNlA-2192 - UACUGGCAAUUCGGCCUGCUUU 22 6041

SCNNlA-2193 - GUACUGGCAAUUCGGCCUGCUUU 23 6042

SCNNlA-2194 - UGUACUGGCAAUUCGGCCUGCUUU 24 6043

SCNNlA-2195 - GCAAUUCGGCCUGCUUUU 18 6044

SCNNlA-2196 - GGCAAUUCGGCCUGCUUUU 19 6045

SCNNlA-34 - UGGCAAUUCGGCCUGCUUUU 20 573

SCNNlA-2197 - CUGGCAAUUCGGCCUGCUUUU 21 6046

SCNNlA-2198 - ACUGGCAAUUCGGCCUGCUUUU 22 6047

SCNNlA-2199 - UACUGGCAAUUCGGCCUGCUUUU 23 6048

SCNNlA-2200 - GUACUGGCAAUUCGGCCUGCUUUU 24 6049

1242

5535.1 Table 44E provides exemplary targeting domains for knocking out the SCNN1A gene selected according to the fifth tier parameters. The targeting domains fall in the coding sequence of the gene, downstream of the first 500bp of coding sequence (e.g., anywhere from +500 (relative to the start codon) to the stop codon of the gene), starts with a 5'G and PAM is

NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 44E

1243

5535.1 SCNNlA-2228 + GUUGCACUGGACACAGAGAC 20 6077

SCNNlA-2229 + GGUUGCACUGGACACAGAGAC 21 6078

SCNNlA-2230 + GCCCCCUGGAGAUGGGCGGGGGCC 24 6079

SCNNlA-2231 + GUACUCCACGUUCUGGGGCC 20 6080

SCNNlA-2232 + GCCCAGCGUGUCCUCCUCC 19 6081

SCNNlA-2233 + GUUGCCCAGCGUGUCCUCCUCC 22 6082

SCNNlA-1051 + GAUCAUGCUCUCCUGGAAGC 20 4900

SCNNlA-2234 + GGAAGGAGGGGAGGAUGC 18 6083

SCNNlA-2235 + GGGAAGGAGGGGAGGAUGC 19 6084

SCNNlA-2236 + GUGGGAAGGAGGGGAGGAUGC 21 6085

SCNNlA-2237 + GAAGUGGGAAGGAGGGGAGGAUGC 24

6086

SCNNlA-2238 + GAUGUCACCGAGGGCCAUC 19 6087

SCNNlA-2239 + GGAUGUCACCGAGGGCCAUC 20 6088

SCNNlA-2240 + GGGAUGUCACCGAGGGCCAUC 21 6089

SCNNlA-2241 + GCCAUAAUCGCCCCCAAGUCUGUC 24 6090

SCNNlA-2242 + GCUGCCCAGGUUGGACAG 18 6091

SCNNlA-2243 + GGCUGCCCAGGUUGGACAG 19 6092

SCNNlA-2244 + GCCCCAGUCACUGUGGACAGCAG 23 6093

SCNNlA-2245 + GGCCCCAGUCACUGUGGACAGCAG 24 6094

SCNNlA-2246 + GACCUAGGGGUGCAGAGAGAG 21 6095

SCNNlA-2247 + GAAUACACACCUGGAAGGGAG 21 6096

SCNNlA-2248 + GUGAAUACACACCUGGAAGGGAG 23 6097

SCNNlA-2249 + GCGCUGCAAGGGGUGCGG 18 6098

SCNNlA-2250 + GGCGCUGCAAGGGGUGCGG 19 6099

SCNNlA-2251 + GCAGAAGUGGGAAGGAGGG 19 6100

SCNNlA-2252 + GGCAGAAGUGGGAAGGAGGG 20 6101

SCNNlA-2253 + GGGCAGAAGUGGGAAGGAGGG 21 6102

SCNNlA-2254 + GGGGCAGAAGUGGGAAGGAGGG 22 6103

SCNNlA-2255 + GGGGGCAGAAGUGGGAAGGAGGG 23 6104

SCNNlA-2256 + GUCCUCCUCCAGGGAUGG 18 6105

SCNNlA-2257 + GUGUCCUCCUCCAGGGAUGG 20 6106

SCNNlA-2258 + GCGUGUCCUCCUCCAGGGAUGG 22 6107

SCNNlA-2259 + GCCUCACCUGCUGUGUGUACUUUG 24 6108

SCNNlA-2260 + GACCCAUUCCUAGGAAAGAAU 21 6109

SCNNlA-2261 + GAAGACCCAUUCCUAGGAAAGAAU 24 6110

SCNNlA-2262 + GACCUACCGUGACAGAGGGAGACU 24 6111

SCNNlA-1263 + GCAGCAUCAGGGACAGACCU 20 5112

SCNNlA-2263 + GCGCAGCAUCAGGGACAGACCU 22 6112

SCNNlA-2264 + GCGCGCAGCAUCAGGGACAGACCU 24 6113

SCNNlA-2265 + GCUUAUAGUAGCAGUACCCU 20 6114

SCNNlA-2266 + GAGCUUAUAGUAGCAGUACCCU 22 6115

1244

5535.1 SCNNlA-2267 + GGAGCUUAUAGUAGCAGUACCCU 23 6116

SCNNlA-2268 + GCUGGUAGCUGGUCACGCU 19 6117

SCNNlA-2269 + GAGCUGGUAGCUGGUCACGCU 21 6118

SCNNlA-2270 + GAGAGCUGGUAGCUGGUCACGCU 23 6119

SCNNlA-2271 + GCAUGGAAGACAUCCAGAGGU 21 6120

SCNNlA-2272 + GGCAUGGAAGACAUCCAGAGGU 22 6121

SCNNlA-2273 + GCUCCUCCAGCUCCUCUUUAAUUU 24 6122

SCNNlA-2274 - GGCAUCUCUCUGUACCCA 18 6123

SCNNlA-2275 - GAACAGGCAUCUCUCUGUACCCA 23 6124

SCNNlA-2276 - GCUUCCAGGAGAGCAUGAUCA 21 6125

SCNNlA-2277 - GACACCCCCAUUCUUUCCUAGGA 23 6126

SCNNlA-2278 - GACAUCCCAGGUAGAGUGUGGGGA 24 6127

SCNNlA-2279 - GACCCUACUCUCUCUUUCCUGAUA 24 6128

SCNNlA-2280 - GAUUAUGGCGACUGCACC 18 6129

SCNNlA-2281 - GCGAUUAUGGCGACUGCACC 20 6130

SCNNlA-2282 - GGCGAUUAUGGCGACUGCACC 21 6131

SCNNlA-2283 - GGGCGAUUAUGGCGACUGCACC 22 6132

SCNNlA-2284 - GGGGCGAUUAUGGCGACUGCACC 23 6133

SCNNlA-2285 - GGGGGCGAUUAUGGCGACUGCACC 24 6134

SCNNlA-2286 - GCAGGUUAGUGUCCCCUUCC 20 6135

SCNNlA-2287 - GACUACAGAAAG CACAG U U CC 21 6136

SCNNlA-2288 - GUGACUACAGAAAGCACAGUUCC 23 6137

SCNNlA-2289 - GACCUCCAUCAGCAUGAGGAAGGC 24 6138

SCNNlA-2290 - GGUCUCCUGCAACCAGGC 18 6139

SCNNlA-2291 - GUCUCCAGGCCGAGGGGGC 19 6140

SCNNlA-1073 - GGUCUCCAGGCCGAGGGGGC 20 4922

SCNNlA-2292 - GUCCACAGUGACUGGGGC 18 6141

SCNNlA-2293 - GCUGUCCACAGUGACUGGGGC 21 6142

SCNNlA-2294 - GCUUCUACCAGACAUACUCAUC 22 6143

SCNNlA-2295 - GUCCCUGAUGCUGCGCGCAGAG 22 6144

SCNNlA-2296 - GCCCUCGGUGACAUCCCAGG 20 6145

SCNNlA-2297 - GGCCCUCGGUGACAUCCCAGG 21 6146

SCNNlA-2298 - GAUGGCCCUCGGUGACAUCCCAGG 24 6147

SCNNlA-2299 - GUAGAGUGUGGGGAAGGG 18 6148

SCNNlA-2300 - GGUAGAGUGUGGGGAAGGG 19 6149

SCNNlA-2301 - GCCCGGGUAAUGGUGCACGGG 21 6150

SCNNlA-2302 - GGCCCGGGUAAUGGUGCACGGG 22 6151

SCNNlA-2303 - GGGCCCGGGUAAUGGUGCACGGG 23 6152

SCNNlA-2304 - GGGGCCCGGGUAAUGGUGCACGGG 24 6153

SCNNlA-2305 - GUGGGGAAGGGAUGGGUG 18 6154

SCNNlA-1236 - GUGUGGGGAAGGGAUGGGUG 20 5085

SCNNlA-2306 - GAGUGUGGGGAAGGGAUGGGUG 22 6155

1245

5535.1 SCNNlA-2307 - GACAAGAACAACUCCAACCU 20 6156

SCNNlA-2308 - GCACCCCUUGCAGCGCCU 18 6157

SCNNlA-2309 - GCCGCACCCCUUGCAGCGCCU 21 6158

SCNNlA-2310 - GACACCCCCAUUCUUUCCU 19 6159

SCNNlA-2311 - GAUGACACCCCCAUUCUUUCCU 22 6160

SCNNlA-2312 - GCUGAACUACAAAACCAAUU 20 6161

SCNNlA-2313 - GAGCUGAACUACAAAACCAAUU 22 6162

SCNNlA-2314 - GGAGCUGAACUACAAAACCAAUU 23 6163

SCNNlA-2315 - GCAGGAUGAACCUGCCUUU 19 6164

SCNNlA-2316 - GGCAGGAUGAACCUGCCUUU 20 6165

SCNNlA-2317 - GGGCAGGAUGAACCUGCCUUU 21 6166

Table 44F provides exemplary targeting domains for knocking out the SCNN1A gene selected according to the six tier parameters. The targeting domains fall in the coding sequence of the gene, downstream of the first 500bp of coding sequence (e.g., anywhere from +500 (relative to the start codon) to the stop codon of the gene) and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 44F

1246

5535.1 SCNNlA-2332 + CAUUUCUUAGGUGUGGGGCA 20 6181

SCNNlA-2333 + CCAUUUCUUAGGUGUGGGGCA 21 6182

SCNNlA-2334 + UCCAUUUCUUAGGUGUGGGGCA 22 6183

SCNNlA-2335 + CUCCAUUUCUUAGGUGUGGGGCA 23 6184

SCNNlA-2336 + ACUCCAUUUCUUAGGUGUGGGGCA 24 6185

SCNNlA-917 + CGGGACCCUCAGGCGCUGCA 20 4766

SCNNlA-2337 + AUUCCUUAUCAGGAAAGA 18 6186

SCNNlA-2338 + AAUUCCUUAUCAGGAAAGA 19 6187

SCNNlA-2339 + UAAUUCCUUAU CAGG AAAG A 20 6188

SCNNlA-2340 + AGUAAUUCCUUAUCAGGAAAGA 22 6189

SCNNlA-2341 + AG AG U AAU U CCU UAU CAGG AAAG A 24 6190

SCNNlA-2342 + AGUCUCUGGCAGCCUCGA 18 6191

SCNNlA-2343 + AGAGUCUCUGGCAGCCUCGA 20 6192

SCNNlA-2344 + CAGAGUCUCUGGCAGCCUCGA 21 6193

SCNNlA-2345 + UGGCAGAGUCUCUGGCAGCCUCGA 24 6194

SCNNlA-2346 + UGCUCUCCUGGAAGCAGGA 19 6195

SCNNlA-2347 + AUGCUCUCCUGGAAGCAGGA 20 6196

SCNNlA-2348 + CAUGCUCUCCUGGAAGCAGGA 21 6197

SCNNlA-2349 + UCAUGCUCUCCUGGAAGCAGGA 22 6198

SCNNlA-2350 + AUCAUGCUCUCCUGGAAGCAGGA 23 6199

SCNNlA-2351 + UGGAAGACCCAUUCCUAGGA 20 6200

SCNNlA-2352 + CUGGAAGACCCAUUCCUAGGA 21 6201

SCNNlA-2353 + UCUGGAAGACCCAUUCCUAGGA 22 6202

SCNNlA-2354 + AUCUGGAAGACCCAUUCCUAGGA 23 6203

SCNNlA-2355 + CAUCUGGAAGACCCAUUCCUAGGA 24 6204

SCNNlA-2356 + CGGCUGCGGGAGCCGGCCAC 20 6205

SCNNlA-2357 + ACGGCUGCGGGAGCCGGCCAC 21 6206

SCNNlA-2358 + CGACGGCUGCGGGAGCCGGCCAC 23 6207

SCNNlA-2359 + UGCACUGGACACAGAGAC 18 6208

SCNNlA-2360 + UUGCACUGGACACAGAGAC 19 6209

SCNNlA-2361 + UGGUUGCACUGGACACAGAGAC 22 6210

SCNNlA-2362 + CUGGUUGCACUGGACACAGAGAC 23 6211

SCNNlA-2363 + UCUGGUUGCACUGGACACAGAGAC 24 6212

SCNNlA-2364 + CCUUCCCCACACUCUACC 18 6213

SCNNlA-2365 + CCCUUCCCCACACUCUACC 19 6214

SCNNlA-1006 + UCCCUUCCCCACACUCUACC 20 4855

SCNNlA-2366 + AUCCCUUCCCCACACUCUACC 21 6215

SCNNlA-2367 + CAUCCCUUCCCCACACUCUACC 22 6216

SCNNlA-2368 + CCAUCCCUUCCCCACACUCUACC 23 6217

SCNNlA-2369 + CCCAUCCCUUCCCCACACUCUACC 24 6218

SCNNlA-2370 + UGGAGAUGGGCGGGGGCC 18 6219

SCNNlA-2371 + CUGGAGAUGGGCGGGGGCC 19 6220

1247

5535.1 SCNNlA-2372 + CCUGGAGAUGGGCGGGGGCC 20 6221

SCNNlA-2373 + CCCUGGAGAUGGGCGGGGGCC 21 6222

SCNNlA-2374 + CCCCUGGAGAUGGGCGGGGGCC 22 6223

SCNNlA-2375 + CCCCCUGGAGAUGGGCGGGGGCC 23 6224

SCNNlA-2376 + ACUCCACGUUCUGGGGCC 18 6225

SCNNlA-2377 + UACUCCACGUUCUGGGGCC 19 6226

SCNNlA-2378 + AGUACUCCACGUUCUGGGGCC 21 6227

SCNNlA-2379 + CAGUACUCCACGUUCUGGGGCC 22 6228

SCNNlA-2380 + ACAGUACUCCACGUUCUGGGGCC 23 6229

SCNNlA-2381 + CACAGUACUCCACGUUCUGGGGCC 24 6230

SCNNlA-2382 + CCCAGCGUGUCCUCCUCC 18 6231

SCNNlA-1038 + UGCCCAGCGUGUCCUCCUCC 20 4887

SCNNlA-2383 + UUGCCCAGCGUGUCCUCCUCC 21 6232

SCNNlA-2384 + AGUUGCCCAGCGUGUCCUCCUCC 23 6233

SCNNlA-2385 + AAGUUGCCCAGCGUGUCCUCCUCC 24 6234

SCNNlA-2386 + UCAUGCUCUCCUGGAAGC 18 6235

SCNNlA-2387 + AUCAUGCUCUCCUGGAAGC 19 6236

SCNNlA-2388 + UGAUCAUGCUCUCCUGGAAGC 21 6237

SCNNlA-2389 + UUGAUCAUGCUCUCCUGGAAGC 22 6238

SCNNlA-2390 + CUUGAUCAUGCUCUCCUGGAAGC 23 6239

SCNNlA-2391 + CCUUGAUCAUGCUCUCCUGGAAGC 24 6240

SCNNlA-2392 + UGGGAAGGAGGGGAGGAUGC 20 6241

SCNNlA-2393 + AGUGGGAAGGAGGGGAGGAUGC 22 6242

SCNNlA-2394 + AAGUGGGAAGGAGGGGAGGAUGC 23 6243

SCNNlA-2395 + AUGUCACCGAGGGCCAUC 18 6244

SCNNlA-2396 + UGGGAUGUCACCGAGGGCCAUC 22 6245

SCNNlA-2397 + CUGGGAUGUCACCGAGGGCCAUC 23 6246

SCNNlA-2398 + CCUGGGAUGUCACCGAGGGCCAUC 24 6247

SCNNlA-2399 + AUCGCCCCCAAGUCUGUC 18 6248

SCNNlA-2400 + AAUCGCCCCCAAGUCUGUC 19 6249

SCNNlA-2401 + UAAUCGCCCCCAAGUCUGUC 20 6250

SCNNlA-2402 + AUAAUCGCCCCCAAGUCUGUC 21 6251

SCNNlA-2403 + CAUAAUCGCCCCCAAGUCUGUC 22 6252

SCNNlA-2404 + CCAUAAUCGCCCCCAAGUCUGUC 23 6253

SCNNlA-2405 + UGGCUGCCCAGGUUGGACAG 20 6254

SCNNlA-2406 + CUGGCUGCCCAGGUUGGACAG 21 6255

SCNNlA-2407 + ACUGGCUGCCCAGGUUGGACAG 22 6256

SCNNlA-2408 + CACUGGCUGCCCAGGUUGGACAG 23 6257

SCNNlA-2409 + CCACUGGCUGCCCAGGUUGGACAG 24 6258

SCNNlA-2410 + AGUCACUGUGGACAGCAG 18 6259

SCNNlA-2411 + CAG U CAC U G U G G ACAG C AG 19 6260

SCNNlA-1119 + CCAGUCACUGUGGACAGCAG 20 4968

1248

5535.1 SCNNlA-2412 + CCCAGUCACUGUGGACAGCAG 21 6261

SCNNlA-2413 + CCCCAGUCACUGUGGACAGCAG 22 6262

SCNNlA-2414 + UUAUCAGGAAAGAGAGAG 18 6263

SCNNlA-2415 + CUUAUCAGGAAAGAGAGAG 19 6264

SCNNlA-2416 + CCUUAUCAGGAAAGAGAGAG 20 6265

SCNNlA-2417 + UCCUUAUCAGGAAAGAGAGAG 21 6266

SCNNlA-2418 + UUCCUUAUCAGGAAAGAGAGAG 22 6267

SCNNlA-2419 + AUUCCUUAU CAGG AAAG AG AG AG 23 6268

SCNNlA-2420 + AAUUCCUUAUCAGGAAAGAGAGAG 24 6269

SCNNlA-2421 + CUAGGGGUGCAGAGAGAG 18 6270

SCNNlA-2422 + CCUAGGGGUGCAGAGAGAG 19 6271

SCNNlA-2423 + ACCUAGGGGUGCAGAGAGAG 20 6272

SCNNlA-2424 + AGACCUAGGGGUGCAGAGAGAG 22 6273

SCNNlA-2425 + CAGACCUAGGGGUGCAGAGAGAG 23 6274

SCNNlA-2426 + ACAGACCUAGGGGUGCAGAGAGAG 24 6275

SCNNlA-2427 + UACACACCUGGAAGGGAG 18 6276

SCNNlA-2428 + AUACACACCUGGAAGGGAG 19 6277

SCNNlA-2429 + AAUACACACCUGGAAGGGAG 20 6278

SCNNlA-2430 + UGAAUACACACCUGGAAGGGAG 22 6279

SCNNlA-2431 + AGUGAAUACACACCUGGAAGGGAG 24 6280

SCNNlA-2432 + AGGCGCUGCAAGGGGUGCGG 20 6281

SCNNlA-2433 + CAGGCGCUGCAAGGGGUGCGG 21 6282

SCNNlA-2434 + UCAGGCGCUGCAAGGGGUGCGG 22 6283

SCNNlA-2435 + CUCAGGCGCUGCAAGGGGUGCGG 23 6284

SCNNlA-2436 + CCUCAGGCGCUGCAAGGGGUGCGG 24 6285

SCNNlA-2437 + CAGAAGUGGGAAGGAGGG 18 6286

SCNNlA-2438 + UGGGGGCAGAAGUGGGAAGGAGGG 24

6287

SCNNlA-2439 + UGUCCUCCUCCAGGGAUGG 19 6288

SCNNlA-2440 + CGUGUCCUCCUCCAGGGAUGG 21 6289

SCNNlA-2441 + AGCGUGUCCUCCUCCAGGGAUGG 23 6290

SCNNlA-2442 + CAGCGUGUCCUCCUCCAGGGAUGG 24 6291

SCNNlA-2443 + UCACCGCAUCCACCCCUG 18 6292

SCNNlA-2444 + CUCACCGCAUCCACCCCUG 19 6293

SCNNlA-2445 + CCUCACCGCAUCCACCCCUG 20 6294

SCNNlA-2446 + CCCUCACCGCAUCCACCCCUG 21 6295

SCNNlA-2447 + UCCCUCACCGCAUCCACCCCUG 22 6296

SCNNlA-2448 + CUCCCUCACCGCAUCCACCCCUG 23 6297

SCNNlA-2449 + ACUCCCUCACCGCAUCCACCCCUG 24 6298

SCNNlA-2450 + CCUGCUGUGUGUACUUUG 18 6299

SCNNlA-2451 + ACCUGCUGUGUGUACUUUG 19 6300

SCNNlA-2452 + CACCUGCUGUGUGUACUUUG 20 6301

1249

5535.1 SCNNlA-2453 + UCACCUGCUGUGUGUACUUUG 21 6302

SCNNlA-2454 + CUCACCUGCUGUGUGUACUUUG 22 6303

SCNNlA-2455 + CCUCACCUGCUGUGUGUACUUUG 23 6304

SCNNlA-2456 + CCAUUCCUAGGAAAGAAU 18 6305

SCNNlA-2457 + CCCAUUCCUAGGAAAGAAU 19 6306

SCNNlA-1244 + ACCCAUUCCUAGGAAAGAAU 20 5093

SCNNlA-2458 + AGACCCAUUCCUAGGAAAGAAU 22 6307

SCNNlA-2459 + AAGACCCAUUCCUAGGAAAGAAU 23 6308

SCNNlA-2460 + CCGUGACAGAGGGAGACU 18 6309

SCNNlA-2461 + ACCGUGACAGAGGGAGACU 19 6310

SCNNlA-2462 + UACCGUGACAGAGGGAGACU 20 6311

SCNNlA-2463 + CUACCGUGACAGAGGGAGACU 21 6312

SCNNlA-2464 + CCUACCGUGACAGAGGGAGACU 22 6313

SCNNlA-2465 + ACCUACCGUGACAGAGGGAGACU 23 6314

SCNNlA-2466 + AGUCCUUCCAGUCCACCU 18 6315

SCNNlA-2467 + CAGUCCUUCCAGUCCACCU 19 6316

SCNNlA-1262 + CCAGUCCUUCCAGUCCACCU 20 5111

SCNNlA-2468 + UCCAGUCCUUCCAGUCCACCU 21 6317

SCNNlA-2469 + UUCCAGUCCUUCCAGUCCACCU 22 6318

SCNNlA-2470 + CUUCCAGUCCUUCCAGUCCACCU 23 6319

SCNNlA-2471 + UCUUCCAGUCCUUCCAGUCCACCU 24 6320

SCNNlA-2472 + AGCAUCAGGGACAGACCU 18 6321

SCNNlA-2473 + CAGCAUCAGGGACAGACCU 19 6322

SCNNlA-2474 + CGCAGCAUCAGGGACAGACCU 21 6323

SCNNlA-2475 + CGCGCAGCAUCAGGGACAGACCU 23 6324

SCNNlA-2476 + UUAUAGUAGCAGUACCCU 18 6325

SCNNlA-2477 + CUUAUAGUAGCAGUACCCU 19 6326

SCNNlA-2478 + AGCUUAUAGUAGCAGUACCCU 21 6327

SCNNlA-2479 + UGGAGCUUAUAGUAGCAGUACCCU 24 6328

SCNNlA-2480 + CUGGUAGCUGGUCACGCU 18 6329

SCNNlA-1274 + AGCUGGUAGCUGGUCACGCU 20 5123

SCNNlA-2481 + AGAGCUGGUAGCUGGUCACGCU 22 6330

SCNNlA-2482 + AGAGAGCUGGUAGCUGGUCACGCU 24 6331

SCNNlA-2483 + ACAUCGGGUGGUGGAAGU 18 6332

SCNNlA-2484 + UACAUCGGGUGGUGGAAGU 19 6333

SCNNlA-2485 + AUACAUCGGGUGGUGGAAGU 20 6334

SCNNlA-2486 + CAUACAUCGGGUGGUGGAAGU 21 6335

SCNNlA-2487 + CCAUACAUCGGGUGGUGGAAGU 22 6336

SCNNlA-2488 + UCCAUACAUCGGGUGGUGGAAGU 23 6337

SCNNlA-2489 + UUCCAUACAUCGGGUGGUGGAAGU 24 6338

SCNNlA-2490 + UGGAAGACAUCCAGAGGU 18 6339

SCNNlA-2491 + AUGGAAGACAUCCAGAGGU 19 6340

1250

5535.1 SCNNlA-1284 + CAUGGAAGACAUCCAGAGGU 20 5133

SCNNlA-2492 + AGGCAUGGAAGACAUCCAGAGGU 23 6341

SCNNlA-2493 + CAGGCAUGGAAGACAUCCAGAGGU 24 6342

SCNNlA-2494 + CCAGCUCCUCUUUAAUUU 18 6343

SCNNlA-2495 + UCCAGCUCCUCUUUAAUUU 19 6344

SCNNlA-2496 + CUCCAGCUCCUCUUUAAUUU 20 6345

SCNNlA-2497 + CCUCCAGCUCCUCUUUAAUUU 21 6346

SCNNlA-2498 + UCCUCCAGCUCCUCUUUAAUUU 22 6347

SCNNlA-2499 + CUCCUCCAGCUCCUCUUUAAUUU 23 6348

SCNNlA-2500 - UGCCCCACACCUAAGAAA 18 6349

SCNNlA-2501 - CUGCCCCACACCUAAGAAA 19 6350

SCNNlA-884 - UCUGCCCCACACCUAAGAAA 20 4733

SCNNlA-2502 - CUCUGCCCCACACCUAAGAAA 21 6351

SCNNlA-2503 - CCUCUGCCCCACACCUAAGAAA 22 6352

SCNNlA-2504 - CCCUCUGCCCCACACCUAAGAAA 23 6353

SCNNlA-2505 - ACCCUCUGCCCCACACCUAAGAAA 24 6354

SCNNlA-2506 - AGGCAUCUCUCUGUACCCA 19 6355

SCNNlA-2507 - CAGGCAUCUCUCUGUACCCA 20 6356

SCNNlA-2508 - ACAGGCAUCUCUCUGUACCCA 21 6357

SCNNlA-2509 - AACAGGCAUCUCUCUGUACCCA 22 6358

SCNNlA-2510 - AGAACAGGCAUCUCUCUGUACCCA 24 6359

SCNNlA-2511 - UCCAGGAGAGCAUGAUCA 18 6360

SCNNlA-2512 - UUCCAGGAGAGCAUGAUCA 19 6361

SCNNlA-923 - CUUCCAGGAGAGCAUGAUCA 20 4772

SCNNlA-2513 - UGCUUCCAGGAGAGCAUGAUCA 22 6362

SCNNlA-2514 - CUGCUUCCAGGAGAGCAUGAUCA 23 6363

SCNNlA-2515 - CCUGCUUCCAGGAGAGCAUGAUCA 24 6364

SCNNlA-2516 - CCCCAUUCUUUCCUAGGA 18 6365

SCNNlA-2517 - CCCCCAUUCUUUCCUAGGA 19 6366

SCNNlA-2518 - ACCCCCAUUCUUUCCUAGGA 20 6367

SCNNlA-2519 - CACCCCCAUUCUUUCCUAGGA 21 6368

SCNNlA-2520 - ACACCCCCAUUCUUUCCUAGGA 22 6369

SCNNlA-2521 - UGACACCCCCAUUCUUUCCUAGGA 24 6370

SCNNlA-2522 - CCAGGUAGAGUGUGGGGA 18 6371

SCNNlA-2523 - CCCAGGUAGAGUGUGGGGA 19 6372

SCNNlA-957 - UCCCAGGUAGAGUGUGGGGA 20 4806

SCNNlA-2524 - AUCCCAGGUAGAGUGUGGGGA 21 6373

SCNNlA-2525 - CAUCCCAGGUAGAGUGUGGGGA 22 6374

SCNNlA-2526 - ACAUCCCAGGUAGAGUGUGGGGA 23 6375

SCNNlA-2527 - CAGGGGUGGAUGCGGUGA 18 6376

SCNNlA-2528 - UCAGGGGUGGAUGCGGUGA 19 6377

SCNNlA-967 - AUCAGGGGUGGAUGCGGUGA 20 4816

1251

5535.1 SCNNlA-2529 - CAUCAGGGGUGGAUGCGGUGA 21 6378

SCNNlA-2530 - UCAUCAGGGGUGGAUGCGGUGA 22 6379

SCNNlA-2531 - CUCAUCAGGGGUGGAUGCGGUGA 23 6380

SCNNlA-2532 - ACUCAUCAGGGGUGGAUGCGGUGA 24 6381

SCNNlA-2533 - ACUCUCUCUUUCCUGAUA 18 6382

SCNNlA-2534 - UACUCUCUCUUUCCUGAUA 19 6383

SCNNlA-971 - CUACUCUCUCUUUCCUGAUA 20 4820

SCNNlA-2535 - CCUACUCUCUCUUUCCUGAUA 21 6384

SCNNlA-2536 - CCCUACUCUCUCUUUCCUGAUA 22 6385

SCNNlA-2537 - ACCCUACUCUCUCUUUCCUGAUA 23 6386

SCNNlA-2538 - CGAUUAUGGCGACUGCACC 19 6387

SCNNlA-2539 - CUGGAUGUCUUCCAUGCC 18 6388

SCNNlA-2540 - UCUGGAUGUCUUCCAUGCC 19 6389

SCNNlA-1033 - CUCUGGAUGUCUUCCAUGCC 20 4882

SCNNlA-2541 - CCUCUGGAUGUCUUCCAUGCC 21 6390

SCNNlA-2542 - ACCUCUGGAUGUCUUCCAUGCC 22 6391

SCNNlA-2543 - AACCUCUGGAUGUCUUCCAUGCC 23 6392

SCNNlA-2544 - CAACCUCUGGAUGUCUUCCAUGCC 24 6393

SCNNlA-2545 - AGGUUAGUGUCCCCUUCC 18 6394

SCNNlA-2546 - CAGGUUAGUGUCCCCUUCC 19 6395

SCNNlA-2547 - UGCAGGUUAGUGUCCCCUUCC 21 6396

SCNNlA-2548 - AUGCAGGUUAGUGUCCCCUUCC 22 6397

SCNNlA-2549 - CAUGCAGGUUAGUGUCCCCUUCC 23 6398

SCNNlA-2550 - CCAUGCAGGUUAGUGUCCCCUUCC 24 6399

SCNNlA-2551 - UACAGAAAG CACAG U U CC 18 6400

SCNNlA-2552 - CUACAGAAAG CACAG U U CC 19 6401

SCNNlA-1047 - ACUACAGAAAGCACAGUUCC 20 4896

SCNNlA-2553 - UGACUACAGAAAG CACAG U U CC 22 6402

SCNNlA-2554 - UGUGACUACAGAAAGCACAGUUCC 24 6403

SCNNlA-2555 - CAUCAGCAUGAGGAAGGC 18 6404

SCNNlA-2556 - CCAUCAGCAUGAGGAAGGC 19 6405

SCNNlA-2557 - UCCAUCAGCAUGAGGAAGGC 20 6406

SCNNlA-2558 - CUCCAUCAGCAUGAGGAAGGC 21 6407

SCNNlA-2559 - CCUCCAUCAGCAUGAGGAAGGC 22 6408

SCNNlA-2560 - ACCUCCAUCAGCAUGAGGAAGGC 23 6409

SCNNlA-2561 - AGGUCUCCUGCAACCAGGC 19 6410

SCNNlA-2562 - CAGGUCUCCUGCAACCAGGC 20 6411

SCNNlA-2563 - CCAGGUCUCCUGCAACCAGGC 21 6412

SCNNlA-2564 - ACCAGGUCUCCUGCAACCAGGC 22 6413

SCNNlA-2565 - AACCAGGUCUCCUGCAACCAGGC 23 6414

SCNNlA-2566 - CAACCAGGUCUCCUGCAACCAGGC 24 6415

SCNNlA-2567 - UCUCCAGGCCGAGGGGGC 18 6416

1252

5535.1 SCNNlA-2568 - UGGUCUCCAGGCCGAGGGGGC 21 6417

SCNNlA-2569 - CUGGUCUCCAGGCCGAGGGGGC 22 6418

SCNNlA-2570 - ACUGGUCUCCAGGCCGAGGGGGC 23 6419

SCNNlA-2571 - UACUGGUCUCCAGGCCGAGGGGGC 24 6420

SCNNlA-2572 - UGUCCACAGUGACUGGGGC 19 6421

SCNNlA-2573 - CUGUCCACAGUGACUGGGGC 20 6422

SCNNlA-2574 - UGCUGUCCACAGUGACUGGGGC 22 6423

SCNNlA-2575 - CUGCUGUCCACAGUGACUGGGGC 23 6424

SCNNlA-2576 - CCUGCUGUCCACAGUGACUGGGGC 24 6425

SCNNlA-2577 - UGUCACGGUAGGUCGUGC 18 6426

SCNNlA-2578 - CUGUCACGGUAGGUCGUGC 19 6427

SCNNlA-2579 - UCUGUCACGGUAGGUCGUGC 20 6428

SCNNlA-2580 - CUCUGUCACGGUAGGUCGUGC 21 6429

SCNNlA-2581 - CCUCUGUCACGGUAGGUCGUGC 22 6430

SCNNlA-2582 - CCCUCUGUCACGGUAGGUCGUGC 23 6431

SCNNlA-2583 - UCCCUCUGUCACGGUAGGUCGUGC 24 6432

SCNNlA-2584 - CUACCAGACAUACUCAUC 18 6433

SCNNlA-2585 - UCUACCAGACAUACUCAUC 19 6434

SCNNlA-1091 - UUCUACCAGACAUACUCAUC 20 4940

SCNNlA-2586 - CUUCUACCAGACAUACUCAUC 21 6435

SCNNlA-2587 - UGCUUCUACCAGACAUACUCAUC 23 6436

SCNNlA-2588 - CUGCUUCUACCAGACAUACUCAUC 24 6437

SCNNlA-2589 - CUGAUGCUGCGCGCAGAG 18 6438

SCNNlA-2590 - CCUGAUGCUGCGCGCAGAG 19 6439

SCNNlA-2591 - CCCUGAUGCUGCGCGCAGAG 20 6440

SCNNlA-2592 - UCCCUGAUGCUGCGCGCAGAG 21 6441

SCNNlA-2593 - UGUCCCUGAUGCUGCGCGCAGAG 23 6442

SCNNlA-2594 - CUGUCCCUGAUGCUGCGCGCAGAG 24 6443

SCNNlA-2595 - AUCCGCGGCCCCAGAACG 18 6444

SCNNlA-2596 - UAUCCGCGGCCCCAGAACG 19 6445

SCNNlA-1144 - CUAUCCGCGGCCCCAGAACG 20 4993

SCNNlA-2597 - UCUAUCCGCGGCCCCAGAACG 21 6446

SCNNlA-2598 - UUCUAUCCGCGGCCCCAGAACG 22 6447

SCNNlA-2599 - CUUCUAUCCGCGGCCCCAGAACG 23 6448

SCNNlA-2600 - UCUUCUAUCCGCGGCCCCAGAACG 24 6449

SCNNlA-2601 - CCUCGGUGACAUCCCAGG 18 6450

SCNNlA-2602 - CCCUCGGUGACAUCCCAGG 19 6451

SCNNlA-2603 - UGGCCCUCGGUGACAUCCCAGG 22 6452

SCNNlA-2604 - AUGGCCCUCGGUGACAUCCCAGG 23 6453

SCNNlA-2605 - AGGUAGAGUGUGGGGAAGGG 20 6454

SCNNlA-2606 - CAGGUAGAGUGUGGGGAAGGG 21 6455

SCNNlA-2607 - CCAGGUAGAGUGUGGGGAAGGG 22 6456

1253

5535.1 SCNNlA-2608 - CCCAGGUAGAGUGUGGGGAAGGG 23 6457

SCNNlA-2609 - UCCCAGGUAGAGUGUGGGGAAGGG 24

6458

SCNNlA-2610 - CAGACAUACUCAUCAGGG 18 6459

SCNNlA-2611 - CCAGACAUACUCAUCAGGG 19 6460

SCNNlA-2612 - ACCAGACAUACUCAUCAGGG 20 6461

SCNNlA-2613 - UACCAGACAUACUCAUCAGGG 21 6462

SCNNlA-2614 - CUACCAGACAUACUCAUCAGGG 22 6463

SCNNlA-2615 - UCUACCAGACAUACUCAUCAGGG 23 6464

SCNNlA-2616 - UUCUACCAGACAUACUCAUCAGGG 24 6465

SCNNlA-2617 - CGGGUAAUGGUGCACGGG 18 6466

SCNNlA-2618 - CCGGGUAAUGGUGCACGGG 19 6467

SCNNlA-2619 - CCCGGGUAAUGGUGCACGGG 20 6468

SCNNlA-2620 - UGUGGGGAAGGGAUGGGUG 19 6469

SCNNlA-2621 - AGUGUGGGGAAGGGAUGGGUG 21 6470

SCNNlA-2622 - AGAGUGUGGGGAAGGGAUGGGUG 23 6471

SCNNlA-2623 - UAGAGUGUGGGGAAGGGAUGGGUG 24

6472

SCNNlA-2624 - CAAG AACAAC U CC AACC U 18 6473

SCNNlA-2625 - ACAAGAACAACUCCAACCU 19 6474

SCNNlA-2626 - UGACAAGAACAACUCCAACCU 21 6475

SCNNlA-2627 - AUGACAAGAACAACUCCAACCU 22 6476

SCNNlA-2628 - AAUGACAAGAACAACUCCAACCU 23 6477

SCNNlA-2629 - CAAUGACAAGAACAACUCCAACCU 24 6478

SCNNlA-2630 - CGCACCCCUUGCAGCGCCU 19 6479

SCNNlA-2631 - CCGCACCCCUUGCAGCGCCU 20 6480

SCNNlA-2632 - UGCCGCACCCCUUGCAGCGCCU 22 6481

SCNNlA-2633 - CUGCCGCACCCCUUGCAGCGCCU 23 6482

SCNNlA-2634 - UCUGCCGCACCCCUUGCAGCGCCU 24 6483

SCNNlA-2635 - ACACCCCCAUUCUUUCCU 18 6484

SCNNlA-1272 - UGACACCCCCAUUCUUUCCU 20 5121

SCNNlA-2636 - AUGACACCCCCAUUCUUUCCU 21 6485

SCNNlA-2637 - UGAUGACACCCCCAUUCUUUCCU 23 6486

SCNNlA-2638 - UUGAUGACACCCCCAUUCUUUCCU 24 6487

SCNNlA-2639 - UGAACU ACAAAACCAAU U 18 6488

SCNNlA-2640 - CUGAACUACAAAACCAAUU 19 6489

SCNNlA-2641 - AGCUGAACUACAAAACCAAUU 21 6490

SCNNlA-2642 - AGGAGCUGAACUACAAAACCAAUU 24 6491

SCNNlA-2643 - CAGGAUGAACCUGCCUUU 18 6492

SCNNlA-2644 - CGGGCAGGAUGAACCUGCCUUU 22 6493

SCNNlA-2645 - ACGGGCAGGAUGAACCUGCCUUU 23 6494

SCNNlA-2646 - CACGGGCAGGAUGAACCUGCCUUU 24 6495

1254

5535.1 Table 44G provides exemplary targeting domains for knocking out the SCNN1A gene selected according to the seven tier parameters. The targeting domains fall in the coding sequence of the gene, downstream of the first 500bp of coding sequence (e.g., anywhere from +500 (relative to the start codon) to the stop codon of the gene) and PAM is NNGRRV. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 44G

1255

5535.1 SCNNlA-2672 + AGAGACAUGGGGUGGGGGCAGAA 23 6521

SCNNlA-2673 + CAGAGACAUGGGGUGGGGGCAGAA 24 6522

SCNNlA-2674 + GUGAAUACACACCUGGAA 18 6523

SCNNlA-2675 + AGUGAAUACACACCUGGAA 19 6524

SCNNlA-892 + GAGUGAAUACACACCUGGAA 20 4741

SCNNlA-2676 + GGAGUGAAUACACACCUGGAA 21 6525

SCNNlA-2677 + AGGAGUGAAUACACACCUGGAA 22 6526

SCNNlA-2678 + CAGGAGUGAAUACACACCUGGAA 23 6527

SCNNlA-2679 + GCAGGAGUGAAUACACACCUGGAA 24 6528

SCNNlA-2680 + AUACAUCGGGUGGUGGAA 18 6529

SCNNlA-2681 + CAUACAUCGGGUGGUGGAA 19 6530

SCNNlA-2682 + CCAUACAUCGGGUGGUGGAA 20 6531

SCNNlA-2683 + UCCAUACAUCGGGUGGUGGAA 21 6532

SCNNlA-2684 + UUCCAUACAUCGGGUGGUGGAA 22 6533

SCNNlA-2685 + UUUCCAUACAUCGGGUGGUGGAA 23 6534

SCNNlA-2686 + GUUUCCAUACAUCGGGUGGUGGAA 24 6535

SCNNlA-2687 + UCUCCACCACAGACAACA 18 6536

SCNNlA-2688 + AUCUCCACCACAGACAACA 19 6537

SCNNlA-2689 + CAU CU CCACCACAG ACAACA 20 6538

SCNNlA-2690 + CCAUCUCCACCACAGACAACA 21 6539

SCNNlA-2691 + GCCAUCUCCACCACAGACAACA 22 6540

SCNNlA-2692 + AGCCAUCUCCACCACAGACAACA 23 6541

SCNNlA-2693 + CAG CCAUCUCCACCACAGACAACA 24 6542

SCNNlA-2694 + UUCUGGUUGCACUGGACA 18 6543

SCNNlA-2695 + GUUCUGGUUGCACUGGACA 19 6544

SCNNlA-2696 + UGUUCUGGUUGCACUGGACA 20 6545

SCNNlA-2697 + UUGUUCUGGUUGCACUGGACA 21 6546

SCNNlA-2698 + UUUGUUCUGGUUGCACUGGACA 22 6547

SCNNlA-2699 + AUUUGUUCUGGUUGCACUGGACA 23 6548

SCNNlA-2700 + GAUUUGUUCUGGUUGCACUGGACA 24 6549

SCNNlA-2701 + GCACGACCUACCGUGACA 18 6550

SCNNlA-2702 + GGCACGACCUACCGUGACA 19 6551

SCNNlA-2703 + AGGCACGACCUACCGUGACA 20 6552

SCNNlA-2704 + CAGGCACGACCUACCGUGACA 21 6553

SCNNlA-2705 + CCAGGCACGACCUACCGUGACA 22 6554

SCNNlA-2706 + UCCAGGCACGACCUACCGUGACA 23 6555

SCNNlA-2707 + AUCCAGGCACGACCUACCGUGACA 24 6556

SCNNlA-2708 + CAGUACCCUGUGGGUACA 18 6557

SCNNlA-2709 + GCAGUACCCUGUGGGUACA 19 6558

SCNNlA-2710 + AGCAGUACCCUGUGGGUACA 20 6559

SCNNlA-2711 + UAGCAGUACCCUGUGGGUACA 21 6560

SCNNlA-2712 + GUAGCAGUACCCUGUGGGUACA 22 6561

1256

5535.1 SCNNlA-2713 + AGUAGCAGUACCCUGUGGGUACA 23 6562

SCNNlA-2714 + UAGUAGCAGUACCCUGUGGGUACA 24 6563

SCNNlA-2715 + CCUCUCAGGGCCCCCCCA 18 6564

SCNNlA-2716 + CCCUCUCAGGGCCCCCCCA 19 6565

SCNNlA-2717 + UCCCUCUCAGGGCCCCCCCA 20 6566

SCNNlA-2718 + UUCCCUCUCAGGGCCCCCCCA 21 6567

SCNNlA-2719 + CUUCCCUCUCAGGGCCCCCCCA 22 6568

SCNNlA-2720 + CCUUCCCUCUCAGGGCCCCCCCA 23 6569

SCNNlA-2721 + UCCUUCCCUCUCAGGGCCCCCCCA 24 6570

SCNNlA-2722 + GGCGCCAUGGAGCAAGCA 18 6571

SCNNlA-2723 + GGGCGCCAUGGAGCAAGCA 19 6572

SCNNlA-909 + AGGGCGCCAUGGAGCAAGCA 20 4758

SCNNlA-2724 + GAGGGCGCCAUGGAGCAAGCA 21 6573

SCNNlA-2725 + AGAGGGCGCCAUGGAGCAAGCA 22 6574

SCNNlA-2726 + CAGAGGGCGCCAUGGAGCAAGCA 23 6575

SCNNlA-2727 + GCAGAGGGCGCCAUGGAGCAAGCA 24 6576

SCNNlA-2728 + CAGUCACUGUGGACAGCA 18 6577

SCNNlA-2729 + CCAGUCACUGUGGACAGCA 19 6578

SCNNlA-910 + CCCAGUCACUGUGGACAGCA 20 4759

SCNNlA-2730 + CCCCAGUCACUGUGGACAGCA 21 6579

SCNNlA-2731 + GCCCCAGUCACUGUGGACAGCA 22 6580

SCNNlA-2732 + GGCCCCAGUCACUGUGGACAGCA 23 6581

SCNNlA-2733 + GGGCCCCAGUCACUGUGGACAGCA 24 6582

SCNNlA-2734 + CAUCGUGAGUAACCAGCA 18 6583

SCNNlA-2735 + CCAUCGUGAGUAACCAGCA 19 6584

SCNNlA-2736 + GCCAUCGUGAGUAACCAGCA 20 6585

SCNNlA-2737 + GGCCAUCGUGAGUAACCAGCA 21 6586

SCNNlA-2738 + GGGCCAUCGUGAGUAACCAGCA 22 6587

SCNNlA-2739 + AGGGCCAUCGUGAGUAACCAGCA 23 6588

SCNNlA-2740 + GAGGGCCAUCGUGAGUAACCAGCA 24 6589

SCNNlA-2741 + CGUUGUUGAUUCCAGGCA 18 6590

SCNNlA-2742 + CCGUUGUUGAUUCCAGGCA 19 6591

SCNNlA-913 + ACCGUUGUUGAUUCCAGGCA 20 4762

SCNNlA-2743 + CACCGUUGUUGAUUCCAGGCA 21 6592

SCNNlA-2744 + UCACCGUUGUUGAUUCCAGGCA 22 6593

SCNNlA-2745 + CUCACCGUUGUUGAUUCCAGGCA 23 6594

SCNNlA-2746 + UCUCACCGUUGUUGAUUCCAGGCA 24 6595

SCNNlA-2747 + CCCAGGGUGGCAUAGGCA 18 6596

SCNNlA-2748 + GCCCAGGGUGGCAUAGGCA 19 6597

SCNNlA-914 + GGCCCAGGGUGGCAUAGGCA 20 4763

SCNNlA-2749 + GGGCCCAGGGUGGCAUAGGCA 21 6598

SCNNlA-2750 + GGGGCCCAGGGUGGCAUAGGCA 22 6599

1257

5535.1 SCNNlA-2751 + GGGGGCCCAGGGUGGCAUAGGCA 23 6600

SCNNlA-2752 + CGGGGGCCCAGGGUGGCAUAGGCA 24 6601

SCNNlA-2753 + GACAGACCUAGGGGUGCA 18 6602

SCNNlA-2754 + GGACAGACCUAGGGGUGCA 19 6603

SCNNlA-2755 + GGGACAGACCUAGGGGUGCA 20 6604

SCNNlA-2756 + AGGGACAGACCUAGGGGUGCA 21 6605

SCNNlA-2757 + CAGGGACAGACCUAGGGGUGCA 22 6606

SCNNlA-2758 + UCAGGGACAGACCUAGGGGUGCA 23 6607

SCNNlA-2759 + AUCAGGGACAGACCUAGGGGUGCA 24 6608

SCNNlA-2760 + CGAUUUGUUCUGGUUGCA 18 6609

SCNNlA-2761 + CCGAUUUGUUCUGGUUGCA 19 6610

SCNNlA-2762 + UCCGAUUUGUUCUGGUUGCA 20 6611

SCNNlA-2763 + GUCCGAUUUGUUCUGGUUGCA 21 6612

SCNNlA-2764 + AGUCCGAUUUGUUCUGGUUGCA 22 6613

SCNNlA-2765 + CAGUCCGAUUUGUUCUGGUUGCA 23 6614

SCNNlA-2766 + GCAGUCCGAUUUGUUCUGGUUGCA 24 6615

SCNNlA-2767 + ACACAGAGACUAGAGUCA 18 6616

SCNNlA-2768 + GACACAGAGACUAGAGUCA 19 6617

SCNNlA-2769 + GGACACAGAGACUAGAGUCA 20 6618

SCNNlA-2770 + UGGACACAGAGACUAGAGUCA 21 6619

SCNNlA-2771 + CUGGACACAGAGACUAGAGUCA 22 6620

SCNNlA-2772 + ACUGGACACAGAGACUAGAGUCA 23 6621

SCNNlA-2773 + CACUGGACACAGAGACUAGAGUCA 24 6622

SCNNlA-2774 + CUGUAUUUGUACAGGUCA 18 6623

SCNNlA-2775 + GCUGUAUUUGUACAGGUCA 19 6624

SCNNlA-2776 + AGCUGUAUUUGUACAGGUCA 20 6625

SCNNlA-2777 + GAGCUGUAUUUGUACAGGUCA 21 6626

SCNNlA-2778 + GGAGCUGUAUUUGUACAGGUCA 22 6627

SCNNlA-2779 + AGGAGCUGUAUUUGUACAGGUCA 23 6628

SCNNlA-2780 + AAGGAGCUGUAUUUGUACAGGUCA 24 6629

SCNNlA-2781 + ACUCUACCUGGGAUGUCA 18 6630

SCNNlA-2782 + CACUCUACCUGGGAUGUCA 19 6631

SCNNlA-2783 + ACACUCUACCUGGGAUGUCA 20 6632

SCNNlA-2784 + CACACUCUACCUGGGAUGUCA 21 6633

SCNNlA-2785 + CCACACUCUACCUGGGAUGUCA 22 6634

SCNNlA-2786 + CCCACACUCUACCUGGGAUGUCA 23 6635

SCNNlA-2787 + CCCCACACUCUACCUGGGAUGUCA 24 6636

SCNNlA-2788 + UUGGAGUUGUUCUUGUCA 18 6637

SCNNlA-2789 + GUUGGAGUUGUUCUUGUCA 19 6638

SCNNlA-2790 + GGUUGGAGUUGUUCUUGUCA 20 6639

SCNNlA-2791 + AGGUUGGAGUUGUUCUUGUCA 21 6640

SCNNlA-2792 + GAGGUUGGAGUUGUUCUUGUCA 22 6641

1258

5535.1 SCNNlA-2793 + AGAGGUUGGAGUUGUUCUUGUCA 23 6642

SCNNlA-2794 + CAGAGGUUGGAGUUGUUCUUGUCA 24

6643

SCNNlA-2795 + ACCCAUUCCUAGGAAAGA 18 6644

SCNNlA-2796 + GACCCAUUCCUAGGAAAGA 19 6645

SCNNlA-2797 + AGACCCAUUCCUAGGAAAGA 20 6646

SCNNlA-2798 + AAGACCCAUUCCUAGGAAAGA 21 6647

SCNNlA-2799 + GAAGACCCAUUCCUAGGAAAGA 22 6648

SCNNlA-2800 + GGAAGACCCAUUCCUAGGAAAGA 23 6649

SCNNlA-2801 + UGGAAGACCCAUUCCUAGGAAAGA 24 6650

SCNNlA-2802 + ACGACCUACCGUGACAGA 18 6651

SCNNlA-2803 + CACGACCUACCGUGACAGA 19 6652

SCNNlA-931 + GCACGACCUACCGUGACAGA 20 4780

SCNNlA-2804 + GGCACGACCUACCGUGACAGA 21 6653

SCNNlA-2805 + AGGCACGACCUACCGUGACAGA 22 6654

SCNNlA-2806 + CAGGCACGACCUACCGUGACAGA 23 6655

SCNNlA-2807 + CCAGGCACGACCUACCGUGACAGA 24 6656

SCNNlA-2808 + CAGACCUAGGGGUGCAGA 18 6657

SCNNlA-2809 + ACAGACCUAGGGGUGCAGA 19 6658

SCNNlA-2810 + GACAGACCUAGGGGUGCAGA 20 6659

SCNNlA-2811 + GGACAGACCUAGGGGUGCAGA 21 6660

SCNNlA-2812 + GGGACAGACCUAGGGGUGCAGA 22 6661

SCNNlA-2813 + AGGGACAGACCUAGGGGUGCAGA 23 6662

SCNNlA-2814 + CAGGGACAGACCUAGGGGUGCAGA 24 6663

SCNNlA-2815 + ACAGAGACUAGAGUCAGA 18 6664

SCNNlA-2816 + CACAGAGACUAGAGUCAGA 19 6665

SCNNlA-933 + ACACAGAGACUAGAGUCAGA 20 4782

SCNNlA-2817 + GACACAGAGACUAGAGUCAGA 21 6666

SCNNlA-2818 + GGACACAGAGACUAGAGUCAGA 22 6667

SCNNlA-2819 + UGGACACAGAGACUAGAGUCAGA 23 6668

SCNNlA-2820 + CUGGACACAGAGACUAGAGUCAGA 24 6669

SCNNlA-2821 + GGCUGUCAAGGCUGGAGA 18 6670

SCNNlA-2822 + GGGCUGUCAAGGCUGGAGA 19 6671

SCNNlA-936 + GGGGCUGUCAAGGCUGGAGA 20 4785

SCNNlA-2823 + AGGGGCUGUCAAGGCUGGAGA 21 6672

SCNNlA-2824 + GAGGGGCUGUCAAGGCUGGAGA 22 6673

SCNNlA-2825 + GGAGGGGCUGUCAAGGCUGGAGA 23 6674

SCNNlA-2826 + GGGAGGGGCUGUCAAGGCUGGAGA 24

6675

SCNNlA-2827 + GGGUACCUGAAGGGGCGA 18 6676

SCNNlA-2828 + CGGGUACCUGAAGGGGCGA 19 6677

SCNNlA-946 + CCGGGUACCUGAAGGGGCGA 20 4795

1259

5535.1 SCNNlA-2829 + UCCGGGUACCUGAAGGGGCGA 21 6678

SCNNlA-2830 + UUCCGGGUACCUGAAGGGGCGA 22 6679

SCNNlA-2831 + UUUCCGGGUACCUGAAGGGGCGA 23 6680

SCNNlA-2832 + AUUUCCGGGUACCUGAAGGGGCGA 24 6681

SCNNlA-2833 + GCCUGGCUGGGACAAGGA 18 6682

SCNNlA-2834 + GGCCUGGCUGGGACAAGGA 19 6683

SCNNlA-2835 + GGGCCUGGCUGGGACAAGGA 20 6684

SCNNlA-2836 + AGGGCCUGGCUGGGACAAGGA 21 6685

SCNNlA-2837 + CAGGGCCUGGCUGGGACAAGGA 22 6686

SCNNlA-2838 + GCAGGGCCUGGCUGGGACAAGGA 23 6687

SCNNlA-2839 + AGCAGGGCCUGGCUGGGACAAGGA 24 6688

SCNNlA-2840 + GGGCAGAAGUGGGAAGGA 18 6689

SCNNlA-2841 + GGGGCAGAAGUGGGAAGGA 19 6690

SCNNlA-948 + GGGGGCAGAAGUGGGAAGGA 20 4797

SCNNlA-2842 + UGGGGGCAGAAGUGGGAAGGA 21 6691

SCNNlA-2843 + GUGGGGGCAGAAGUGGGAAGGA 22 6692

SCNNlA-2844 + GGUGGGGGCAGAAGUGGGAAGGA 23 6693

SCNNlA-2845 + GGGUGGGGGCAGAAGUGGGAAGGA 24

6694

SCNNlA-2846 + AGUAAUUCCUUAUCAGGA 18 6695

SCNNlA-2847 + GAGUAAUUCCUUAUCAGGA 19 6696

SCNNlA-2848 + AGAGUAAUUCCUUAUCAGGA 20 6697

SCNNlA-2849 + GAGAGUAAUUCCUUAUCAGGA 21 6698

SCNNlA-2850 + UGAGAGUAAUUCCUUAUCAGGA 22 6699

SCNNlA-2851 + GUGAGAGUAAUUCCUUAUCAGGA 23 6700

SCNNlA-2852 + AGUGAGAGUAAUUCCUUAUCAGGA 24 6701

SCNNlA-2853 + GGAGGAGGGUGGAGAGGA 18 6702

SCNNlA-2854 + GGGAGGAGGGUGGAGAGGA 19 6703

SCNNlA-2855 + AGGGAGGAGGGUGGAGAGGA 20 6704

SCNNlA-2856 + AAGGGAGGAGGGUGGAGAGGA 21 6705

SCNNlA-2857 + GAAGGGAGGAGGGUGGAGAGGA 22 6706

SCNNlA-2858 + GGAAGGGAGGAGGGUGGAGAGGA 23 6707

SCNNlA-2859 + UGGAAGGGAGGAGGGUGGAGAGGA 24

6708

SCNNlA-2860 + ACGUUCUGGGGCCGCGGA 18 6709

SCNNlA-2861 + CACGUUCUGGGGCCGCGGA 19 6710

SCNNlA-2862 + CCACGUUCUGGGGCCGCGGA 20 6711

SCNNlA-2863 + UCCACGUUCUGGGGCCGCGGA 21 6712

SCNNlA-2864 + CUCCACGUUCUGGGGCCGCGGA 22 6713

SCNNlA-2865 + ACUCCACGUUCUGGGGCCGCGGA 23 6714

SCNNlA-2866 + UACUCCACGUUCUGGGGCCGCGGA 24 6715

SCNNlA-2867 + ACUGUGGACAGCAGGGGA 18 6716

1260

5535.1 SCNNlA-2868 + CACUGUGGACAGCAGGGGA 19 6717

SCNNlA-2869 + UCACUGUGGACAGCAGGGGA 20 6718

SCNNlA-2870 + GUCACUGUGGACAGCAGGGGA 21 6719

SCNNlA-2871 + AGUCACUGUGGACAGCAGGGGA 22 6720

SCNNlA-2872 + CAGUCACUGUGGACAGCAGGGGA 23 6721

SCNNlA-2873 + CCAGUCACUGUGGACAGCAGGGGA 24 6722

SCNNlA-2874 + AGCUGGUCACGCUGGGGA 18 6723

SCNNlA-2875 + UAGCUGGUCACGCUGGGGA 19 6724

SCNNlA-956 + GUAGCUGGUCACGCUGGGGA 20 4805

SCNNlA-2876 + GGUAGCUGGUCACGCUGGGGA 21 6725

SCNNlA-2877 + UGGUAGCUGGUCACGCUGGGGA 22 6726

SCNNlA-2878 + CUGGUAGCUGGUCACGCUGGGGA 23 6727

SCNNlA-2879 + GCUGGUAGCUGGUCACGCUGGGGA 24 6728

SCNNlA-2880 + GUGGGGGCAGAAGUGGGA 18 6729

SCNNlA-2881 + GGUGGGGGCAGAAGUGGGA 19 6730

SCNNlA-958 + GGGUGGGGGCAGAAGUGGGA 20 4807

SCNNlA-2882 + GGGGUGGGGGCAGAAGUGGGA 21 6731

SCNNlA-2883 + UGGGGUGGGGGCAGAAGUGGGA 22 6732

SCNNlA-2884 + AUGGGGUGGGGGCAGAAGUGGGA 23 6733

SCNNlA-2885 + CAUGGGGUGGGGGCAGAAGUGGGA 24

6734

SCNNlA-2886 + AGUGAAUACACACCUGGA 18 6735

SCNNlA-2887 + GAGUGAAUACACACCUGGA 19 6736

SCNNlA-960 + GGAGUGAAUACACACCUGGA 20 4809

SCNNlA-2888 + AGGAGUGAAUACACACCUGGA 21 6737

SCNNlA-2889 + CAGGAGUGAAUACACACCUGGA 22 6738

SCNNlA-2890 + GCAGGAGUGAAUACACACCUGGA 23 6739

SCNNlA-2891 + AGCAGGAGUGAAUACACACCUGGA 24 6740

SCNNlA-2892 + GGGGCUGUCAAGGCUGGA 18 6741

SCNNlA-2893 + AGGGGCUGUCAAGGCUGGA 19 6742

SCNNlA-2894 + GAGGGGCUGUCAAGGCUGGA 20 6743

SCNNlA-2895 + GGAGGGGCUGUCAAGGCUGGA 21 6744

SCNNlA-2896 + GGGAGGGGCUGUCAAGGCUGGA 22 6745

SCNNlA-2897 + GGGGAGGGGCUGUCAAGGCUGGA 23 6746

SCNNlA-2898 + GGGGGAGGGGCUGUCAAGGCUGGA 24

6747

SCNNlA-2899 + GGAAGGGAGGAGGGUGGA 18 6748

SCNNlA-2900 + UGGAAGGGAGGAGGGUGGA 19 6749

SCNNlA-2901 + CUGGAAGGGAGGAGGGUGGA 20 6750

SCNNlA-2902 + CCUGGAAGGGAGGAGGGUGGA 21 6751

SCNNlA-2903 + ACCUGGAAGGGAGGAGGGUGGA 22 6752

SCNNlA-2904 + CACCUGGAAGGGAGGAGGGUGGA 23 6753

1261

5535.1 SCNNlA-2905 + ACACCUGGAAGGGAGGAGGGUGGA 24 6754

SCNNlA-2906 + CUGGCUGCCCAGGUUGGA 18 6755

SCNNlA-2907 + ACUGGCUGCCCAGGUUGGA 19 6756

SCNNlA-2908 + CACUGGCUGCCCAGGUUGGA 20 6757

SCNNlA-2909 + CCACUGGCUGCCCAGGUUGGA 21 6758

SCNNlA-2910 + UCCACUGGCUGCCCAGGUUGGA 22 6759

SCNNlA-2911 + CUCCACUGGCUGCCCAGGUUGGA 23 6760

SCNNlA-2912 + GCUCCACUGGCUGCCCAGGUUGGA 24 6761

SCNNlA-2913 + UAAUUUCCGGGUACCUGA 18 6762

SCNNlA-2914 + UUAAUUUCCGGGUACCUGA 19 6763

SCNNlA-964 + UUUAAUUUCCGGGUACCUGA 20 4813

SCNNlA-2915 + CUUUAAUUUCCGGGUACCUGA 21 6764

SCNNlA-2916 + UCUUUAAUUUCCGGGUACCUGA 22 6765

SCNNlA-2917 + CUCUUUAAUUUCCGGGUACCUGA 23 6766

SCNNlA-2918 + CCUCUUUAAUUUCCGGGUACCUGA 24 6767

SCNNlA-2919 + UUGCCUUCCUCAUGCUGA 18 6768

SCNNlA-2920 + CUUGCCUUCCUCAUGCUGA 19 6769

SCNNlA-966 + CCUUGCCUUCCUCAUGCUGA 20 4815

SCNNlA-2921 + UCCUUGCCUUCCUCAUGCUGA 21 6770

SCNNlA-2922 + AUCCUUGCCUUCCUCAUGCUGA 22 6771

SCNNlA-2923 + CAUCCUUGCCUUCCUCAUGCUGA 23 6772

SCNNlA-2924 + GCAUCCUUGCCUUCCUCAUGCUGA 24 6773

SCNNlA-2925 + AGGCACGACCUACCGUGA 18 6774

SCNNlA-2926 + CAGGCACGACCUACCGUGA 19 6775

SCNNlA-2927 + CCAGGCACGACCUACCGUGA 20 6776

SCNNlA-2928 + UCCAGGCACGACCUACCGUGA 21 6777

SCNNlA-2929 + AUCCAGGCACGACCUACCGUGA 22 6778

SCNNlA-2930 + CAUCCAGGCACGACCUACCGUGA 23 6779

SCNNlA-2931 + CCAUCCAGGCACGACCUACCGUGA 24 6780

SCNNlA-2932 + CGGCCACGAGAGUGGUGA 18 6781

SCNNlA-2933 + CCGGCCACGAGAGUGGUGA 19 6782

SCNNlA-968 + GCCGGCCACGAGAGUGGUGA 20 4817

SCNNlA-2934 + AGCCGGCCACGAGAGUGGUGA 21 6783

SCNNlA-2935 + GAGCCGGCCACGAGAGUGGUGA 22 6784

SCNNlA-2936 + GGAGCCGGCCACGAGAGUGGUGA 23 6785

SCNNlA-2937 + GGGAGCCGGCCACGAGAGUGGUGA 24 6786

SCNNlA-2938 + GAGGGUGACCAUCUGUGA 18 6787

SCNNlA-2939 + GGAGGGUGACCAUCUGUGA 19 6788

SCNNlA-2940 + AGGAGGGUGACCAUCUGUGA 20 6789

SCNNlA-2941 + CAGGAGGGUGACCAUCUGUGA 21 6790

SCNNlA-2942 + ACAGGAGGGUGACCAUCUGUGA 22 6791

SCNNlA-2943 + GACAGGAGGGUGACCAUCUGUGA 23 6792

1262

5535.1 SCNNlA-2944 + GGACAGGAGGGUGACCAUCUGUGA 24 6793

SCNNlA-2945 + AGCAGUACCCUGUGGGUA 18 6794

SCNNlA-2946 + UAGCAGUACCCUGUGGGUA 19 6795

SCNNlA-2947 + GUAGCAGUACCCUGUGGGUA 20 6796

SCNNlA-2948 + AGUAGCAGUACCCUGUGGGUA 21 6797

SCNNlA-2949 + UAGUAGCAGUACCCUGUGGGUA 22 6798

SCNNlA-2950 + AUAGUAGCAGUACCCUGUGGGUA 23 6799

SCNNlA-2951 + UAUAGUAGCAGUACCCUGUGGGUA 24 6800

SCNNlA-2952 + CGACAGGAUGUUGAUGUA 18 6801

SCNNlA-2953 + UCGACAGGAUGUUGAUGUA 19 6802

SCNNlA-2954 + CUCGACAGGAUGUUGAUGUA 20 6803

SCNNlA-2955 + CCUCGACAGGAUGUUGAUGUA 21 6804

SCNNlA-2956 + GCCUCGACAGGAUGUUGAUGUA 22 6805

SCNNlA-2957 + AGCCUCGACAGGAUGUUGAUGUA 23 6806

SCNNlA-2958 + CAGCCUCGACAGGAUGUUGAUGUA 24 6807

SCNNlA-2959 + AGGGUAAAGGUUCUCAAC 18 6808

SCNNlA-2960 + AAGGGUAAAGGUUCUCAAC 19 6809

SCNNlA-978 + GAAGGGUAAAGGUUCUCAAC 20 4827

SCNNlA-2961 + UGAAGGGUAAAGGUUCUCAAC 21 6810

SCNNlA-2962 + UUGAAGGGUAAAGGUUCUCAAC 22 6811

SCNNlA-2963 + UUUGAAGGGUAAAGGUUCUCAAC 23 6812

SCNNlA-2964 + CUUUGAAGGGUAAAGGUUCUCAAC 24 6813

SCNNlA-2965 + GUCUGAGGAGAAGUCAAC 18 6814

SCNNlA-2966 + GGUCUGAGGAGAAGUCAAC 19 6815

SCNNlA-2967 + U G G U C U GAG GAG AAG U CAAC 20 6816

SCNNlA-2968 + GUGGUCUGAGGAGAAGUCAAC 21 6817

SCNNlA-2969 + GGUGGUCUGAGGAGAAGUCAAC 22 6818

SCNNlA-2970 + AGGUGGUCUGAGGAGAAGUCAAC 23 6819

SCNNlA-2971 + CAG G U G G U C U GAG GAG AAG U CAAC 24 6820

SCNNlA-2972 + GCAGGAGUGAAUACACAC 18 6821

SCNNlA-2973 + AGCAGGAGUGAAUACACAC 19 6822

SCNNlA-2974 + AAGCAGGAGUGAAUACACAC 20 6823

SCNNlA-2975 + GAAGCAGGAGUGAAUACACAC 21 6824

SCNNlA-2976 + GGAAGCAGGAGUGAAUACACAC 22 6825

SCNNlA-2977 + UGGAAGCAGGAGUGAAUACACAC 23 6826

SCNNlA-2978 + CUGGAAGCAGGAGUGAAUACACAC 24 6827

SCNNlA-2979 + CCAGUCCUUCCAGUCCAC 18 6828

SCNNlA-2980 + UCCAGUCCUUCCAGUCCAC 19 6829

SCNNlA-2981 + UUCCAGUCCUUCCAGUCCAC 20 6830

SCNNlA-2982 + CUUCCAGUCCUUCCAGUCCAC 21 6831

SCNNlA-2983 + UCUUCCAGUCCUUCCAGUCCAC 22 6832

SCNNlA-2984 + AUCUUCCAGUCCUUCCAGUCCAC 23 6833

1263

5535.1 SCNNlA-2985 + GAUCUUCCAGUCCUUCCAGUCCAC 24 6834

SCNNlA-2986 + UGGGACAAGGACAGAGAC 18 6835

SCNNlA-2987 + CUGGGACAAGGACAGAGAC 19 6836

SCNNlA-2988 + GCUGGGACAAGGACAGAGAC 20 6837

SCNNlA-2989 + GGCUGGGACAAGGACAGAGAC 21 6838

SCNNlA-2990 + UGGCUGGGACAAGGACAGAGAC 22 6839

SCNNlA-2991 + CUGGCUGGGACAAGGACAGAGAC 23 6840

SCNNlA-2992 + CCUGGCUGGGACAAGGACAGAGAC 24 6841

SCNNlA-2993 + GCAGGGCCUGGCUGGGAC 18 6842

SCNNlA-2994 + AGCAGGGCCUGGCUGGGAC 19 6843

SCNNlA-2995 + GAGCAGGGCCUGGCUGGGAC 20 6844

SCNNlA-2996 + GGAGCAGGGCCUGGCUGGGAC 21 6845

SCNNlA-2997 + GGGAGCAGGGCCUGGCUGGGAC 22 6846

SCNNlA-2998 + AGGGAGCAGGGCCUGGCUGGGAC 23 6847

SCNNlA-2999 + GAGGGAGCAGGGCCUGGCUGGGAC 24 6848

SCNNlA-3000 + UGGCUGCCCAGGUUGGAC 18 6849

SCNNlA-3001 + CUGGCUGCCCAGGUUGGAC 19 6850

SCNNlA-991 + ACUGGCUGCCCAGGUUGGAC 20 4840

SCNNlA-3002 + CACUGGCUGCCCAGGUUGGAC 21 6851

SCNNlA-3003 + CCACUGGCUGCCCAGGUUGGAC 22 6852

SCNNlA-3004 + UCCACUGGCUGCCCAGGUUGGAC 23 6853

SCNNlA-3005 + CUCCACUGGCUGCCCAGGUUGGAC 24 6854

SCNNlA-3006 + CCCUUCCCCACACUCUAC 18 6855

SCNNlA-3007 + UCCCUUCCCCACACUCUAC 19 6856

SCNNlA-3008 + AUCCCUUCCCCACACUCUAC 20 6857

SCNNlA-3009 + CAUCCCUUCCCCACACUCUAC 21 6858

SCNNlA-3010 + CCAUCCCUUCCCCACACUCUAC 22 6859

SCNNlA-3011 + CCCAUCCCUUCCCCACACUCUAC 23 6860

SCNNlA-3012 + ACCCAUCCCUUCCCCACACUCUAC 24 6861

SCNNlA-3013 + UCUUUAAUUUCCGGGUAC 18 6862

SCNNlA-3014 + CUCUUUAAUUUCCGGGUAC 19 6863

SCNNlA-3015 + CCUCUUUAAUUUCCGGGUAC 20 6864

SCNNlA-3016 + UCCUCUUUAAUUUCCGGGUAC 21 6865

SCNNlA-3017 + CUCCUCUUUAAUUUCCGGGUAC 22 6866

SCNNlA-3018 + GCUCCUCUUUAAUUUCCGGGUAC 23 6867

SCNNlA-3019 + AGCUCCUCUUUAAUUUCCGGGUAC 24 6868

SCNNlA-3020 + CUGCCCGUGCACCAUUAC 18 6869

SCNNlA-3021 + CCUGCCCGUGCACCAUUAC 19 6870

SCNNlA-3022 + UCCUGCCCGUGCACCAUUAC 20 6871

SCNNlA-3023 + AUCCUGCCCGUGCACCAUUAC 21 6872

SCNNlA-3024 + CAUCCUGCCCGUGCACCAUUAC 22 6873

SCNNlA-3025 + UCAUCCUGCCCGUGCACCAUUAC 23 6874

1264

5535.1 SCNNlA-3026 + UUCAUCCUGCCCGUGCACCAUUAC 24 6875

SCNNlA-3027 + UCUGAGGAGAAGUCAACC 18 6876

SCNNlA-3028 + GUCUGAGGAGAAGUCAACC 19 6877

SCNNlA-1000 + GGUCUGAGGAGAAGUCAACC 20 4849

SCNNlA-3029 + UGGUCUGAGGAGAAGUCAACC 21 6878

SCNNlA-3030 + GUGGUCUGAGGAGAAGUCAACC 22 6879

SCNNlA-3031 + GGUGGUCUGAGGAGAAGUCAACC 23 6880

SCNNlA-3032 + AGGUGGUCUGAGGAGAAGUCAACC 24 6881

SCNNlA-3033 + UCCACCACAGACAACACC 18 6882

SCNNlA-3034 + CUCCACCACAGACAACACC 19 6883

SCNNlA-3035 + UCUCCACCACAGACAACACC 20 6884

SCNNlA-3036 + AUCUCCACCACAGACAACACC 21 6885

SCNNlA-3037 + CAUCUCCACCACAGACAACACC 22 6886

SCNNlA-3038 + CCAUCUCCACCACAGACAACACC 23 6887

SCNNlA-3039 + GCCAUCUCCACCACAGACAACACC 24 6888

SCNNlA-3040 + CAGGAGUGAAUACACACC 18 6889

SCNNlA-3041 + GCAGGAGUGAAUACACACC 19 6890

SCNNlA-1002 + AGCAGGAGUGAAUACACACC 20 4851

SCNNlA-3042 + AAGCAGGAGUGAAUACACACC 21 6891

SCNNlA-3043 + GAAGCAGGAGUGAAUACACACC 22 6892

SCNNlA-3044 + GGAAGCAGGAGUGAAUACACACC 23 6893

SCNNlA-3045 + UGGAAGCAGGAGUGAAUACACACC 24 6894

SCNNlA-3046 + UAUGAACCCACAUACACC 18 6895

SCNNlA-3047 + CUAUGAACCCACAUACACC 19 6896

SCNNlA-3048 + CCUAUGAACCCACAUACACC 20 6897

SCNNlA-3049 + UCCUAUGAACCCACAUACACC 21 6898

SCNNlA-3050 + UUCCUAUGAACCCACAUACACC 22 6899

SCNNlA-3051 + UUUCCUAUGAACCCACAUACACC 23 6900

SCNNlA-3052 + GUUUCCUAUGAACCCACAUACACC 24 6901

SCNNlA-3053 + CAGUCCUUCCAGUCCACC 18 6902

SCNNlA-3054 + CCAGUCCUUCCAGUCCACC 19 6903

SCNNlA-1004 + UCCAGUCCUUCCAGUCCACC 20 4853

SCNNlA-3055 + UUCCAGUCCUUCCAGUCCACC 21 6904

SCNNlA-3056 + CUUCCAGUCCUUCCAGUCCACC 22 6905

SCNNlA-3057 + UCUUCCAGUCCUUCCAGUCCACC 23 6906

SCNNlA-3058 + AUCUUCCAGUCCUUCCAGUCCACC 24 6907

SCNNlA-3059 + UCUACCUGGGAUGUCACC 18 6908

SCNNlA-3060 + CUCUACCUGGGAUGUCACC 19 6909

SCNNlA-3061 + ACUCUACCUGGGAUGUCACC 20 6910

SCNNlA-3062 + CACUCUACCUGGGAUGUCACC 21 6911

SCNNlA-3063 + ACACUCUACCUGGGAUGUCACC 22 6912

SCNNlA-3064 + CACACUCUACCUGGGAUGUCACC 23 6913

1265

5535.1 SCNNlA-3065 + CCACACUCUACCUGGGAUGUCACC 24 6914

SCNNlA-3066 + CAGCAUCAGGGACAGACC 18 6915

SCNNlA-3067 + GCAGCAUCAGGGACAGACC 19 6916

SCNNlA-3068 + CGCAGCAUCAGGGACAGACC 20 6917

SCNNlA-3069 + GCGCAGCAUCAGGGACAGACC 21 6918

SCNNlA-3070 + CGCGCAGCAUCAGGGACAGACC 22 6919

SCNNlA-3071 + GCGCGCAGCAUCAGGGACAGACC 23 6920

SCNNlA-3072 + UGCGCGCAGCAUCAGGGACAGACC 24 6921

SCNNlA-3073 + CUCCCUGGAGUCUCACCC 18 6922

SCNNlA-3074 + GCUCCCUGGAGUCUCACCC 19 6923

SCNNlA-3075 + GGCUCCCUGGAGUCUCACCC 20 6924

SCNNlA-3076 + GGGCUCCCUGGAGUCUCACCC 21 6925

SCNNlA-3077 + GGGGCUCCCUGGAGUCUCACCC 22 6926

SCNNlA-3078 + GGGGGCUCCCUGGAGUCUCACCC 23 6927

SCNNlA-3079 + UGGGGGCUCCCUGGAGUCUCACCC 24 6928

SCNNlA-3080 + UCCCUGGAGUCUCACCCC 18 6929

SCNNlA-3081 + CUCCCUGGAGUCUCACCCC 19 6930

SCNNlA-1013 + GCUCCCUGGAGUCUCACCCC 20 4862

SCNNlA-3082 + GGCUCCCUGGAGUCUCACCCC 21 6931

SCNNlA-3083 + GGGCUCCCUGGAGUCUCACCCC 22 6932

SCNNlA-3084 + GGGGCUCCCUGGAGUCUCACCCC 23 6933

SCNNlA-3085 + GGGGGCUCCCUGGAGUCUCACCCC 24 6934

SCNNlA-3086 + UCCCUCUCAGGGCCCCCC 18 6935

SCNNlA-3087 + UUCCCUCUCAGGGCCCCCC 19 6936

SCNNlA-3088 + CUUCCCUCUCAGGGCCCCCC 20 6937

SCNNlA-3089 + CCUUCCCUCUCAGGGCCCCCC 21 6938

SCNNlA-3090 + UCCUUCCCUCUCAGGGCCCCCC 22 6939

SCNNlA-3091 + CUCCUUCCCUCUCAGGGCCCCCC 23 6940

SCNNlA-3092 + UCUCCUUCCCUCUCAGGGCCCCCC 24 6941

SCNNlA-3093 + GGCCCCUGCAGAGCCCCC 18 6942

SCNNlA-3094 + UGGCCCCUGCAGAGCCCCC 19 6943

SCNNlA-1015 + CUGGCCCCUGCAGAGCCCCC 20 4864

SCNNlA-3095 + ACUGGCCCCUGCAGAGCCCCC 21 6944

SCNNlA-3096 + AACUGGCCCCUGCAGAGCCCCC 22 6945

SCNNlA-3097 + GAACUGGCCCCUGCAGAGCCCCC 23 6946

SCNNlA-3098 + GGAACUGGCCCCUGCAGAGCCCCC 24 6947

SCNNlA-3099 + UGGCCCCUGCAGAGCCCC 18 6948

SCNNlA-3100 + CUGGCCCCUGCAGAGCCCC 19 6949

SCNNlA-3101 + ACUGGCCCCUGCAGAGCCCC 20 6950

SCNNlA-3102 + AACUGGCCCCUGCAGAGCCCC 21 6951

SCNNlA-3103 + GAACUGGCCCCUGCAGAGCCCC 22 6952

SCNNlA-3104 + GGAACUGGCCCCUGCAGAGCCCC 23 6953

1266

5535.1 SCNNlA-3105 + AGGAACUGGCCCCUGCAGAGCCCC 24 6954

SCNNlA-3106 + ACGGGCUCGACGGGCCCC 18 6955

SCNNlA-3107 + UACGGGCUCGACGGGCCCC 19 6956

SCNNlA-3108 + CUACGGGCUCGACGGGCCCC 20 6957

SCNNlA-3109 + GCUACGGGCUCGACGGGCCCC 21 6958

SCNNlA-3110 + CGCUACGGGCUCGACGGGCCCC 22 6959

SCNNlA-3111 + ACGCUACGGGCUCGACGGGCCCC 23 6960

SCNNlA-3112 + CACGCUACGGGCUCGACGGGCCCC 24 6961

SCNNlA-3113 + CGGCUGCGGGAGCCGGCC 18 6962

SCNNlA-3114 + ACGGCUGCGGGAGCCGGCC 19 6963

SCNNlA-3115 + GACGGCUGCGGGAGCCGGCC 20 6964

SCNNlA-3116 + CGACGGCUGCGGGAGCCGGCC 21 6965

SCNNlA-3117 + GCGACGGCUGCGGGAGCCGGCC 22 6966

SCNNlA-3118 + CGCGACGGCUGCGGGAGCCGGCC 23 6967

SCNNlA-3119 + UCGCGACGGCUGCGGGAGCCGGCC 24 6968

SCNNlA-3120 + ACCCCUGCCCCCUCGGCC 18 6969

SCNNlA-3121 + CACCCCUGCCCCCUCGGCC 19 6970

SCNNlA-1030 + GCACCCCUGCCCCCUCGGCC 20 4879

SCNNlA-3122 + AGCACCCCUGCCCCCUCGGCC 21 6971

SCNNlA-3123 + GAGCACCCCUGCCCCCUCGGCC 22 6972

SCNNlA-3124 + UGAGCACCCCUGCCCCCUCGGCC 23 6973

SCNNlA-3125 + CUGAGCACCCCUGCCCCCUCGGCC 24 6974

SCNNlA-3126 + GUUUUGUAGUUCAGCUCC 18 6975

SCNNlA-3127 + GGUUUUGUAGUUCAGCUCC 19 6976

SCNNlA-3128 + UGGUUUUGUAGUUCAGCUCC 20 6977

SCNNlA-3129 + UUGGUUUUGUAGUUCAGCUCC 21 6978

SCNNlA-3130 + AUUGGUUUUGUAGUUCAGCUCC 22 6979

SCNNlA-3131 + AAUUGGUUUUGUAGUUCAGCUCC 23 6980

SCNNlA-3132 + GAAUUGGUUUUGUAGUUCAGCUCC 24 6981

SCNNlA-3133 + UCCUUGAUCAUGCUCUCC 18 6982

SCNNlA-3134 + CUCCUUGAUCAUGCUCUCC 19 6983

SCNNlA-1041 + ACUCCUUGAUCAUGCUCUCC 20 4890

SCNNlA-3135 + CACUCCUUGAUCAUGCUCUCC 21 6984

SCNNlA-3136 + ACACUCCUUGAUCAUGCUCUCC 22 6985

SCNNlA-3137 + CACACUCCUUGAUCAUGCUCUCC 23 6986

SCNNlA-3138 + CCACACUCCUUGAUCAUGCUCUCC 24 6987

SCNNlA-3139 + AUCUGGAAGACCCAUUCC 18 6988

SCNNlA-3140 + CAUCUGGAAGACCCAUUCC 19 6989

SCNNlA-3141 + GCAUCUGGAAGACCCAUUCC 20 6990

SCNNlA-3142 + AGCAUCUGGAAGACCCAUUCC 21 6991

SCNNlA-3143 + UAGCAUCUGGAAGACCCAUUCC 22 6992

SCNNlA-3144 + AUAGCAUCUGGAAGACCCAUUCC 23 6993

1267

5535.1 SCNNlA-3145 + GAUAGCAUCUGGAAGACCCAUUCC 24 6994

SCNNlA-3146 + GGGCGCCAUGGAGCAAGC 18 6995

SCNNlA-3147 + AGGGCGCCAUGGAGCAAGC 19 6996

SCNNlA-1049 + GAGGGCGCCAUGGAGCAAGC 20 4898

SCNNlA-3148 + AGAGGGCGCCAUGGAGCAAGC 21 6997

SCNNlA-3149 + CAGAGGGCGCCAUGGAGCAAGC 22 6998

SCNNlA-3150 + GCAGAGGGCGCCAUGGAGCAAGC 23 6999

SCNNlA-3151 + AGCAGAGGGCGCCAUGGAGCAAGC 24 7000

SCNNlA-3152 + GGUUGUUGUCCCGCAAGC 18 7001

SCNNlA-3153 + GGGUUGUUGUCCCGCAAGC 19 7002

SCNNlA-1050 + GGGGUUGUUGUCCCGCAAGC 20 4899

SCNNlA-3154 + GGGGGUUGUUGUCCCGCAAGC 21 7003

SCNNlA-3155 + UGGGGGUUGUUGUCCCGCAAGC 22 7004

SCNNlA-3156 + CUGGGGGUUGUUGUCCCGCAAGC 23 7005

SCNNlA-3157 + CCUGGGGGUUGUUGUCCCGCAAGC 24 7006

SCNNlA-3158 + CCAGUCACUGUGGACAGC 18 7007

SCNNlA-3159 + CCCAGUCACUGUGGACAGC 19 7008

SCNNlA-1053 + CCCCAGUCACUGUGGACAGC 20 4902

SCNNlA-3160 + GCCCCAGUCACUGUGGACAGC 21 7009

SCNNlA-3161 + GGCCCCAGUCACUGUGGACAGC 22 7010

SCNNlA-3162 + GGGCCCCAGUCACUGUGGACAGC 23 7011

SCNNlA-3163 + CGGGCCCCAGUCACUGUGGACAGC 24 7012

SCNNlA-3164 + GCUGCGGGCCUCACCAGC 18 7013

SCNNlA-3165 + CGCUGCGGGCCUCACCAGC 19 7014

SCNNlA-1054 + GCGCUGCGGGCCUCACCAGC 20 4903

SCNNlA-3166 + GGCGCUGCGGGCCUCACCAGC 21 7015

SCNNlA-3167 + CGGCGCUGCGGGCCUCACCAGC 22 7016

SCNNlA-3168 + UCGGCGCUGCGGGCCUCACCAGC 23 7017

SCNNlA-3169 + CUCGGCGCUGCGGGCCUCACCAGC 24 7018

SCNNlA-3170 + CGGAACCUUCGGAGCAGC 18 7019

SCNNlA-3171 + UCGGAACCUUCGGAGCAGC 19 7020

SCNNlA-3172 + UUCGGAACCUUCGGAGCAGC 20 7021

SCNNlA-3173 + CUUCGGAACCUUCGGAGCAGC 21 7022

SCNNlA-3174 + GCUUCGGAACCUUCGGAGCAGC 22 7023

SCNNlA-3175 + GGCUUCGGAACCUUCGGAGCAGC 23 7024

SCNNlA-3176 + CGGCUUCGGAACCUUCGGAGCAGC 24 7025

SCNNlA-3177 + GCUGGUAGCUGGUCACGC 18 7026

SCNNlA-3178 + AGCUGGUAGCUGGUCACGC 19 7027

SCNNlA-1064 + GAGCUGGUAGCUGGUCACGC 20 4913

SCNNlA-3179 + AGAGCUGGUAGCUGGUCACGC 21 7028

SCNNlA-3180 + GAGAGCUGGUAGCUGGUCACGC 22 7029

SCNNlA-3181 + AGAGAGCUGGUAGCUGGUCACGC 23 7030

1268

5535.1 SCNNlA-3182 + CAGAGAGCUGGUAGCUGGUCACGC 24 7031

SCNNlA-3183 + GGGAGGGGCUGUCAAGGC 18 7032

SCNNlA-3184 + GGGGAGGGGCUGUCAAGGC 19 7033

SCNNlA-1067 + GGGGGAGGGGCUGUCAAGGC 20 4916

SCNNlA-3185 + AGGGGGAGGGGCUGUCAAGGC 21 7034

SCNNlA-3186 + CAGGGGGAGGGGCUGUCAAGGC 22 7035

SCNNlA-3187 + GCAGGGGGAGGGGCUGUCAAGGC 23 7036

SCNNlA-3188 + GGCAGGGGGAGGGGCUGUCAAGGC 24 7037

SCNNlA-3189 + CCGUUGUUGAUUCCAGGC 18 7038

SCNNlA-3190 + ACCGUUGUUGAUUCCAGGC 19 7039

SCNNlA-3191 + CACCGUUGUUGAUUCCAGGC 20 7040

SCNNlA-3192 + UCACCGUUGUUGAUUCCAGGC 21 7041

SCNNlA-3193 + CUCACCGUUGUUGAUUCCAGGC 22 7042

SCNNlA-3194 + UCUCACCGUUGUUGAUUCCAGGC 23 7043

SCNNlA-3195 + UUCUCACCGUUGUUGAUUCCAGGC 24 7044

SCNNlA-3196 + CGACGGGCCCCGUGAGGC 18 7045

SCNNlA-3197 + UCGACGGGCCCCGUGAGGC 19 7046

SCNNlA-1068 + CUCGACGGGCCCCGUGAGGC 20 4917

SCNNlA-3198 + GCUCGACGGGCCCCGUGAGGC 21 7047

SCNNlA-3199 + GGCUCGACGGGCCCCGUGAGGC 22 7048

SCNNlA-3200 + GGGCUCGACGGGCCCCGUGAGGC 23 7049

SCNNlA-3201 + CGGGCUCGACGGGCCCCGUGAGGC 24 7050

SCNNlA-3202 + GCCCAGGGUGGCAUAGGC 18 7051

SCNNlA-3203 + GGCCCAGGGUGGCAUAGGC 19 7052

SCNNlA-1069 + GGGCCCAGGGUGGCAUAGGC 20 4918

SCNNlA-3204 + GGGGCCCAGGGUGGCAUAGGC 21 7053

SCNNlA-3205 + GGGGGCCCAGGGUGGCAUAGGC 22 7054

SCNNlA-3206 + CGGGGGCCCAGGGUGGCAUAGGC 23 7055

SCNNlA-3207 + GCGGGGGCCCAGGGUGGCAUAGGC 24 7056

SCNNlA-3208 + CACCCCUGCCCCCUCGGC 18 7057

SCNNlA-3209 + GCACCCCUGCCCCCUCGGC 19 7058

SCNNlA-3210 + AGCACCCCUGCCCCCUCGGC 20 7059

SCNNlA-3211 + GAGCACCCCUGCCCCCUCGGC 21 7060

SCNNlA-3212 + UGAGCACCCCUGCCCCCUCGGC 22 7061

SCNNlA-3213 + CUGAGCACCCCUGCCCCCUCGGC 23 7062

SCNNlA-3214 + CCUGAGCACCCCUGCCCCCUCGGC 24 7063

SCNNlA-3215 + CCGGGUACCUGAAGGGGC 18 7064

SCNNlA-3216 + UCCGGGUACCUGAAGGGGC 19 7065

SCNNlA-3217 + UUCCGGGUACCUGAAGGGGC 20 7066

SCNNlA-3218 + UUUCCGGGUACCUGAAGGGGC 21 7067

SCNNlA-3219 + AUUUCCGGGUACCUGAAGGGGC 22 7068

SCNNlA-3220 + AAUUUCCGGGUACCUGAAGGGGC 23 7069

1269

5535.1 SCNNlA-3221 + UAAUUUCCGGGUACCUGAAGGGGC 24 7070

SCNNlA-3222 + AGCCCCCUGGAGAUGGGC 18 7071

SCNNlA-3223 + GAGCCCCCUGGAGAUGGGC 19 7072

SCNNlA-1075 + AGAGCCCCCUGGAGAUGGGC 20 4924

SCNNlA-3224 + CAGAGCCCCCUGGAGAUGGGC 21 7073

SCNNlA-3225 + GCAGAGCCCCCUGGAGAUGGGC 22 7074

SCNNlA-3226 + UGCAGAGCCCCCUGGAGAUGGGC 23 7075

SCNNlA-3227 + CUGCAGAGCCCCCUGGAGAUGGGC 24 7076

SCNNlA-3228 + GAGGGAGCAGGGCCUGGC 18 7077

SCNNlA-3229 + AGAGGGAGCAGGGCCUGGC 19 7078

SCNNlA-1076 + GAGAGGGAGCAGGGCCUGGC 20 4925

SCNNlA-3230 + GGAGAGGGAGCAGGGCCUGGC 21 7079

SCNNlA-3231 + UGGAGAGGGAGCAGGGCCUGGC 22 7080

SCNNlA-3232 + CUGGAGAGGGAGCAGGGCCUGGC 23 7081

SCNNlA-3233 + GCUGGAGAGGGAGCAGGGCCUGGC 24 7082

SCNNlA-3234 + GGGACCCUCAGGCGCUGC 18 7083

SCNNlA-3235 + CGGGACCCUCAGGCGCUGC 19 7084

SCNNlA-3236 + GCGGGACCCUCAGGCGCUGC 20 7085

SCNNlA-3237 + GGCGGGACCCUCAGGCGCUGC 21 7086

SCNNlA-3238 + GGGCGGGACCCUCAGGCGCUGC 22 7087

SCNNlA-3239 + GGGGCGGGACCCUCAGGCGCUGC 23 7088

SCNNlA-3240 + GGGGGCGGGACCCUCAGGCGCUGC 24 7089

SCNNlA-3241 + GCAGGUCGCGACGGCUGC 18 7090

SCNNlA-3242 + CGCAGGUCGCGACGGCUGC 19 7091

SCNNlA-1082 + CCGCAGGUCGCGACGGCUGC 20 4931

SCNNlA-3243 + CCCGCAGGUCGCGACGGCUGC 21 7092

SCNNlA-3244 + CCCCGCAGGUCGCGACGGCUGC 22 7093

SCNNlA-3245 + CCCCCGCAGGUCGCGACGGCUGC 23 7094

SCNNlA-3246 + UCCCCCGCAGGUCGCGACGGCUGC 24 7095

SCNNlA-3247 + UGACUCACGCCUGGUUGC 18 7096

SCNNlA-3248 + CUGACUCACGCCUGGUUGC 19 7097

SCNNlA-1087 + ACUGACUCACGCCUGGUUGC 20 4936

SCNNlA-3249 + GACUGACUCACGCCUGGUUGC 21 7098

SCNNlA-3250 + GGACUGACUCACGCCUGGUUGC 22 7099

SCNNlA-3251 + AGGACUGACUCACGCCUGGUUGC 23 7100

SCNNlA-3252 + CAGGACUGACUCACGCCUGGUUGC 24 7101

SCNNlA-3253 + CCAGGCAUGGAAGACAUC 18 7102

SCNNlA-3254 + UCCAGGCAUGGAAGACAUC 19 7103

SCNNlA-3255 + UUCCAGGCAUGGAAGACAUC 20 7104

SCNNlA-3256 + AUUCCAGGCAUGGAAGACAUC 21 7105

SCNNlA-3257 + GAUUCCAGGCAUGGAAGACAUC 22 7106

SCNNlA-3258 + UGAUUCCAGGCAUGGAAGACAUC 23 7107

1270

5535.1 SCNNlA-3259 + UUGAUUCCAGGCAUGGAAGACAUC 24 7108

SCNNlA-3260 + UGCUCUGCGCGCAGCAUC 18 7109

SCNNlA-3261 + CUGCUCUGCGCGCAGCAUC 19 7110

SCNNlA-1089 + UCUGCUCUGCGCGCAGCAUC 20 4938

SCNNlA-3262 + UUCUGCUCUGCGCGCAGCAUC 21 7111

SCNNlA-3263 + AUUCUGCUCUGCGCGCAGCAUC 22 7112

SCNNlA-3264 + CAUUCUGCUCUGCGCGCAGCAUC 23 7113

SCNNlA-3265 + UCAUUCUGCUCUGCGCGCAGCAUC 24 7114

SCNNlA-3266 + UUCUGUCGCGAUAGCAUC 18 7115

SCNNlA-3267 + GUUCUGUCGCGAUAGCAUC 19 7116

SCNNlA-1090 + UGUUCUGUCGCGAUAGCAUC 20 4939

SCNNlA-3268 + UUGUUCUGUCGCGAUAGCAUC 21 7117

SCNNlA-3269 + AUUGUUCUGUCGCGAUAGCAUC 22 7118

SCNNlA-3270 + AAUUGUUCUGUCGCGAUAGCAUC 23 7119

SCNNlA-3271 + UAAUUGUUCUGUCGCGAUAGCAUC 24 7120

SCNNlA-3272 + UGAGAGUAAUUCCUUAUC 18 7121

SCNNlA-3273 + GUGAGAGUAAUUCCUUAUC 19 7122

SCNNlA-1092 + AGUGAGAGUAAUUCCUUAUC 20 4941

SCNNlA-3274 + AAGUGAGAGUAAUUCCUUAUC 21 7123

SCNNlA-3275 + GAAGUGAGAGUAAUUCCUUAUC 22 7124

SCNNlA-3276 + GGAAGUGAGAGUAAUUCCUUAUC 23 7125

SCNNlA-3277 + UGGAAGUGAGAGUAAUUCCUUAUC 24 7126

SCNNlA-3278 + CAGGGUGGAGGCUACCUC 18 7127

SCNNlA-3279 + CCAGGGUGGAGGCUACCUC 19 7128

SCNNlA-3280 + GCCAGGGUGGAGGCUACCUC 20 7129

SCNNlA-3281 + UGCCAGGGUGGAGGCUACCUC 21 7130

SCNNlA-3282 + AUGCCAGGGUGGAGGCUACCUC 22 7131

SCNNlA-3283 + GAUGCCAGGGUGGAGGCUACCUC 23 7132

SCNNlA-3284 + GGAUGCCAGGGUGGAGGCUACCUC 24 7133

SCNNlA-3285 + GCCCAGCGUGUCCUCCUC 18 7134

SCNNlA-3286 + UGCCCAGCGUGUCCUCCUC 19 7135

SCNNlA-3287 + UUGCCCAGCGUGUCCUCCUC 20 7136

SCNNlA-3288 + GUUGCCCAGCGUGUCCUCCUC 21 7137

SCNNlA-3289 + AGUUGCCCAGCGUGUCCUCCUC 22 7138

SCNNlA-3290 + AAGUUGCCCAGCGUGUCCUCCUC 23 7139

SCNNlA-3291 + GAAGUUGCCCAGCGUGUCCUCCUC 24 7140

SCNNlA-3292 + CUCCUUGAUCAUGCUCUC 18 7141

SCNNlA-3293 + ACUCCUUGAUCAUGCUCUC 19 7142

SCNNlA-3294 + CACUCCUUGAUCAUGCUCUC 20 7143

SCNNlA-3295 + ACACUCCUUGAUCAUGCUCUC 21 7144

SCNNlA-3296 + CACACUCCUUGAUCAUGCUCUC 22 7145

SCNNlA-3297 + CCACACUCCUUGAUCAUGCUCUC 23 7146

1271

5535.1 SCNNlA-3298 + GCCACACUCCUUGAUCAUGCUCUC 24 7147

SCNNlA-3299 + UCACAGUACUCCACGUUC 18 7148

SCNNlA-3300 + GUCACAGUACUCCACGUUC 19 7149

SCNNlA-1103 + AGUCACAGUACUCCACGUUC 20 4952

SCNNlA-3301 + UAGUCACAGUACUCCACGUUC 21 7150

SCNNlA-3302 + GUAGUCACAGUACUCCACGUUC 22 7151

SCNNlA-3303 + UGUAGUCACAGUACUCCACGUUC 23 7152

SCNNlA-3304 + CUGUAGUCACAGUACUCCACGUUC 24 7153

SCNNlA-3305 + AUGACCAGCAGGUCAAAG 18 7154

SCNNlA-3306 + GAUGACCAGCAGGUCAAAG 19 7155

SCNNlA-3307 + UGAUGACCAGCAGGUCAAAG 20 7156

SCNNlA-3308 + AUGAUGACCAGCAGGUCAAAG 21 7157

SCNNlA-3309 + CAUGAUGACCAGCAGGUCAAAG 22 7158

SCNNlA-3310 + ACAUGAUGACCAGCAGGUCAAAG 23 7159

SCNNlA-3311 + AACAUGAUGACCAGCAGGUCAAAG 24 7160

SCNNlA-3312 + AGGGCGCCAUGGAGCAAG 18 7161

SCNNlA-3313 + GAGGGCGCCAUGGAGCAAG 19 7162

SCNNlA-3314 + AGAGGGCGCCAUGGAGCAAG 20 7163

SCNNlA-3315 + CAGAGGGCGCCAUGGAGCAAG 21 7164

SCNNlA-3316 + GCAGAGGGCGCCAUGGAGCAAG 22 7165

SCNNlA-3317 + AGCAGAGGGCGCCAUGGAGCAAG 23 7166

SCNNlA-3318 + AAGCAGAGGGCGCCAUGGAGCAAG 24 7167

SCNNlA-3319 + GGGUUGUUGUCCCGCAAG 18 7168

SCNNlA-3320 + GGGGUUGUUGUCCCGCAAG 19 7169

SCNNlA-3321 + GGGGGUUGUUGUCCCGCAAG 20 7170

SCNNlA-3322 + UGGGGGUUGUUGUCCCGCAAG 21 7171

SCNNlA-3323 + CUGGGGGUUGUUGUCCCGCAAG 22 7172

SCNNlA-3324 + CCUGGGGGUUGUUGUCCCGCAAG 23 7173

SCNNlA-3325 + ACCUGGGGGUUGUUGUCCCGCAAG 24 7174

SCNNlA-3326 + AUGGGGUGGGGGCAGAAG 18 7175

SCNNlA-3327 + CAUGGGGUGGGGGCAGAAG 19 7176

SCNNlA-1109 + ACAUGGGGUGGGGGCAGAAG 20 4958

SCNNlA-3328 + GACAUGGGGUGGGGGCAGAAG 21 7177

SCNNlA-3329 + AGACAUGGGGUGGGGGCAGAAG 22 7178

SCNNlA-3330 + GAGACAUGGGGUGGGGGCAGAAG 23 7179

SCNNlA-3331 + AGAGACAUGGGGUGGGGGCAGAAG 24

7180

SCNNlA-3332 + UUGAAGCGGCAGGCGAAG 18 7181

SCNNlA-3333 + GUUGAAGCGGCAGGCGAAG 19 7182

SCNNlA-3334 + GGUUGAAGCGGCAGGCGAAG 20 7183

SCNNlA-3335 + UGGUUGAAGCGGCAGGCGAAG 21 7184

SCNNlA-3336 + CUGGUUGAAGCGGCAGGCGAAG 22 7185

1272

5535.1 SCNNlA-3337 + CCUGGUUGAAGCGGCAGGCGAAG 23 7186

SCNNlA-3338 + ACCUGGUUGAAGCGGCAGGCGAAG 24 7187

SCNNlA-3339 + GGGGGCAGAAGUGGGAAG 18 7188

SCNNlA-3340 + UGGGGGCAGAAGUGGGAAG 19 7189

SCNNlA-3341 + GUGGGGGCAGAAGUGGGAAG 20 7190

SCNNlA-3342 + GGUGGGGGCAGAAGUGGGAAG 21 7191

SCNNlA-3343 + GGGUGGGGGCAGAAGUGGGAAG 22 7192

SCNNlA-3344 + GGGGUGGGGGCAGAAGUGGGAAG 23 7193

SCNNlA-3345 + UGGGGUGGGGGCAGAAGUGGGAAG 24

7194

SCNNlA-3346 + AUCAUGCUCUCCUGGAAG 18 7195

SCNNlA-3347 + GAUCAUGCUCUCCUGGAAG 19 7196

SCNNlA-3348 + UGAUCAUGCUCUCCUGGAAG 20 7197

SCNNlA-3349 + UUGAUCAUGCUCUCCUGGAAG 21 7198

SCNNlA-3350 + CUUGAUCAUGCUCUCCUGGAAG 22 7199

SCNNlA-3351 + CCUUGAUCAUGCUCUCCUGGAAG 23 7200

SCNNlA-3352 + UCCUUGAUCAUGCUCUCCUGGAAG 24 7201

SCNNlA-3353 + GGCCCCCCCAGAGGACAG 18 7202

SCNNlA-3354 + GGGCCCCCCCAGAGGACAG 19 7203

SCNNlA-3355 + AGGGCCCCCCCAGAGGACAG 20 7204

SCNNlA-3356 + CAGGGCCCCCCCAGAGGACAG 21 7205

SCNNlA-3357 + UCAGGGCCCCCCCAGAGGACAG 22 7206

SCNNlA-3358 + CUCAGGGCCCCCCCAGAGGACAG 23 7207

SCNNlA-3359 + UCUCAGGGCCCCCCCAGAGGACAG 24 7208

SCNNlA-3360 + CCCAGUCACUGUGGACAG 18 7209

SCNNlA-3361 + CCCCAGUCACUGUGGACAG 19 7210

SCNNlA-3362 + GCCCCAGUCACUGUGGACAG 20 7211

SCNNlA-3363 + GGCCCCAGUCACUGUGGACAG 21 7212

SCNNlA-3364 + GGGCCCCAGUCACUGUGGACAG 22 7213

SCNNlA-3365 + CGGGCCCCAGUCACUGUGGACAG 23 7214

SCNNlA-3366 + CCGGGCCCCAGUCACUGUGGACAG 24 7215

SCNNlA-3367 + CACGACCUACCGUGACAG 18 7216

SCNNlA-3368 + GCACGACCUACCGUGACAG 19 7217

SCNNlA-1114 + GGCACGACCUACCGUGACAG 20 4963

SCNNlA-3369 + AGGCACGACCUACCGUGACAG 21 7218

SCNNlA-3370 + CAGGCACGACCUACCGUGACAG 22 7219

SCNNlA-3371 + CCAGGCACGACCUACCGUGACAG 23 7220

SCNNlA-3372 + UCCAGGCACGACCUACCGUGACAG 24 7221

SCNNlA-3373 + GCCAUCGUGAGUAACCAG 18 7222

SCNNlA-3374 + GGCCAUCGUGAGUAACCAG 19 7223

SCNNlA-3375 + GGGCCAUCGUGAGUAACCAG 20 7224

SCNNlA-3376 + AGGGCCAUCGUGAGUAACCAG 21 7225

1273

5535.1 SCNNlA-3377 + GAGGGCCAUCGUGAGUAACCAG 22 7226

SCNNlA-3378 + CGAGGGCCAUCGUGAGUAACCAG 23 7227

SCNNlA-3379 + CCGAGGGCCAUCGUGAGUAACCAG 24 7228

SCNNlA-3380 + CGCUGCGGGCCUCACCAG 18 7229

SCNNlA-3381 + GCGCUGCGGGCCUCACCAG 19 7230

SCNNlA-3382 + GGCGCUGCGGGCCUCACCAG 20 7231

SCNNlA-3383 + CGGCGCUGCGGGCCUCACCAG 21 7232

SCNNlA-3384 + UCGGCGCUGCGGGCCUCACCAG 22 7233

SCNNlA-3385 + CUCGGCGCUGCGGGCCUCACCAG 23 7234

SCNNlA-3386 + CCUCGGCGCUGCGGGCCUCACCAG 24 7235

SCNNlA-3387 + CCAGGGUGGCAUAGGCAG 18 7236

SCNNlA-3388 + CCCAGGGUGGCAUAGGCAG 19 7237

SCNNlA-1120 + GCCCAGGGUGGCAUAGGCAG 20 4969

SCNNlA-3389 + GGCCCAGGGUGGCAUAGGCAG 21 7238

SCNNlA-3390 + GGGCCCAGGGUGGCAUAGGCAG 22 7239

SCNNlA-3391 + GGGGCCCAGGGUGGCAUAGGCAG 23 7240

SCNNlA-3392 + GGGGGCCCAGGGUGGCAUAGGCAG 24 7241

SCNNlA-3393 + ACCUGGUUGAAGCGGCAG 18 7242

SCNNlA-3394 + GACCUGGUUGAAGCGGCAG 19 7243

SCNNlA-3395 + AGACCUGGUUGAAGCGGCAG 20 7244

SCNNlA-3396 + GAGACCUGGUUGAAGCGGCAG 21 7245

SCNNlA-3397 + GGAGACCUGGUUGAAGCGGCAG 22 7246

SCNNlA-3398 + AGGAGACCUGGUUGAAGCGGCAG 23 7247

SCNNlA-3399 + CAGGAGACCUGGUUGAAGCGGCAG 24 7248

SCNNlA-3400 + CACAGAGACUAGAGUCAG 18 7249

SCNNlA-3401 + ACACAGAGACUAGAGUCAG 19 7250

SCNNlA-1125 + GACACAGAGACUAGAGUCAG 20 4974

SCNNlA-3402 + GGACACAGAGACUAGAGUCAG 21 7251

SCNNlA-3403 + UGGACACAGAGACUAGAGUCAG 22 7252

SCNNlA-3404 + CUGGACACAGAGACUAGAGUCAG 23 7253

SCNNlA-3405 + ACUGGACACAGAGACUAGAGUCAG 24 7254

SCNNlA-3406 + AGGGAGGAGGGUGGAGAG 18 7255

SCNNlA-3407 + AAGGGAGGAGGGUGGAGAG 19 7256

SCNNlA-3408 + GAAGGGAGGAGGGUGGAGAG 20 7257

SCNNlA-3409 + GGAAGGGAGGAGGGUGGAGAG 21 7258

SCNNlA-3410 + UGGAAGGGAGGAGGGUGGAGAG 22 7259

SCNNlA-3411 + CUGGAAGGGAGGAGGGUGGAGAG 23 7260

SCNNlA-3412 + CCUGGAAGGGAGGAGGGUGGAGAG 24

7261

SCNNlA-3413 + GGUGACCAUCUGUGAGAG 18 7262

SCNNlA-3414 + GGGUGACCAUCUGUGAGAG 19 7263

SCNNlA-3415 + AGGGUGACCAUCUGUGAGAG 20 7264

1274

5535.1 SCNNlA-3416 + GAGGGUGACCAUCUGUGAGAG 21 7265

SCNNlA-3417 + GGAGGGUGACCAUCUGUGAGAG 22 7266

SCNNlA-3418 + AGGAGGGUGACCAUCUGUGAGAG 23 7267

SCNNlA-3419 + CAGGAGGGUGACCAUCUGUGAGAG 24 7268

SCNNlA-3420 + GGUACCUGAAGGGGCGAG 18 7269

SCNNlA-3421 + GGGUACCUGAAGGGGCGAG 19 7270

SCNNlA-1130 + CGGGUACCUGAAGGGGCGAG 20 4979

SCNNlA-3422 + CCGGGUACCUGAAGGGGCGAG 21 7271

SCNNlA-3423 + UCCGGGUACCUGAAGGGGCGAG 22 7272

SCNNlA-3424 + UUCCGGGUACCUGAAGGGGCGAG 23 7273

SCNNlA-3425 + UUUCCGGGUACCUGAAGGGGCGAG 24 7274

SCNNlA-3426 + GGCAGAAGUGGGAAGGAG 18 7275

SCNNlA-3427 + GGGCAGAAGUGGGAAGGAG 19 7276

SCNNlA-1132 + GGGGCAGAAGUGGGAAGGAG 20 4981

SCNNlA-3428 + GGGGGCAGAAGUGGGAAGGAG 21 7277

SCNNlA-3429 + UGGGGGCAGAAGUGGGAAGGAG 22 7278

SCNNlA-3430 + GUGGGGGCAGAAGUGGGAAGGAG 23 7279

SCNNlA-3431 + GGUGGGGGCAGAAGUGGGAAGGAG 24

7280

SCNNlA-3432 + ACAGACAACACCGAGGAG 18 7281

SCNNlA-3433 + CACAGACAACACCGAGGAG 19 7282

SCNNlA-3434 + CCACAGACAACACCGAGGAG 20 7283

SCNNlA-3435 + ACCACAGACAACACCGAGGAG 21 7284

SCNNlA-3436 + CACCACAGACAACACCGAGGAG 22 7285

SCNNlA-3437 + CCACCACAGACAACACCGAGGAG 23 7286

SCNNlA-3438 + UCCACCACAGACAACACCGAGGAG 24 7287

SCNNlA-3439 + UCAAGGCUGGAGAGGGAG 18 7288

SCNNlA-3440 + GUCAAGGCUGGAGAGGGAG 19 7289

SCNNlA-3441 + UGUCAAGGCUGGAGAGGGAG 20 7290

SCNNlA-3442 + CUGUCAAGGCUGGAGAGGGAG 21 7291

SCNNlA-3443 + GCUGUCAAGGCUGGAGAGGGAG 22 7292

SCNNlA-3444 + GGCUGUCAAGGCUGGAGAGGGAG 23 7293

SCNNlA-3445 + GGGCUGUCAAGGCUGGAGAGGGAG 24

7294

SCNNlA-3446 + CUGCAGAGCCCCCUGGAG 18 7295

SCNNlA-3447 + CCUGCAGAGCCCCCUGGAG 19 7296

SCNNlA-3448 + CCCUGCAGAGCCCCCUGGAG 20 7297

SCNNlA-3449 + CCCCUGCAGAGCCCCCUGGAG 21 7298

SCNNlA-3450 + GCCCCUGCAGAGCCCCCUGGAG 22 7299

SCNNlA-3451 + GGCCCCUGCAGAGCCCCCUGGAG 23 7300

SCNNlA-3452 + UGGCCCCUGCAGAGCCCCCUGGAG 24 7301

SCNNlA-3453 + GGGCUGUCAAGGCUGGAG 18 7302

1275

5535.1 SCNNlA-3454 + GGGGCUGUCAAGGCUGGAG 19 7303

SCNNlA-1138 + AGGGGCUGUCAAGGCUGGAG 20 4987

SCNNlA-3455 + GAGGGGCUGUCAAGGCUGGAG 21 7304

SCNNlA-3456 + GGAGGGGCUGUCAAGGCUGGAG 22 7305

SCNNlA-3457 + GGGAGGGGCUGUCAAGGCUGGAG 23 7306

SCNNlA-3458 + GGGGAGGGGCUGUCAAGGCUGGAG 24

7307

SCNNlA-3459 + GAAGGGAGGAGGGUGGAG 18 7308

SCNNlA-3460 + GGAAGGGAGGAGGGUGGAG 19 7309

SCNNlA-1139 + UGGAAGGGAGGAGGGUGGAG 20 4988

SCNNlA-3461 + CUGGAAGGGAGGAGGGUGGAG 21 7310

SCNNlA-3462 + CCUGGAAGGGAGGAGGGUGGAG 22 7311

SCNNlA-3463 + ACCUGGAAGGGAGGAGGGUGGAG 23 7312

SCNNlA-3464 + CACCUGGAAGGGAGGAGGGUGGAG 24 7313

SCNNlA-3465 + CAGCCCAGGUGGUCUGAG 18 7314

SCNNlA-3466 + ACAGCCCAGGUGGUCUGAG 19 7315

SCNNlA-3467 + AA CAGCCCAGGUGGUCUGAG 20 7316

SCNNlA-3468 + AAACAGCCCAGGUGGUCUGAG 21 7317

SCNNlA-3469 + GAAA CAGCCCAGGUGGUCUGAG 22 7318

SCNNlA-3470 + UGAAA CAGCCCAGGUGGUCUGAG 23 7319

SCNNlA-3471 + GUGAAA CAGCCCAGGUGGUCUGAG 24 7320

SCNNlA-3472 + CUCGACGGGCCCCGUGAG 18 7321

SCNNlA-3473 + GCUCGACGGGCCCCGUGAG 19 7322

SCNNlA-3474 + GGCUCGACGGGCCCCGUGAG 20 7323

SCNNlA-3475 + GGGCUCGACGGGCCCCGUGAG 21 7324

SCNNlA-3476 + CGGGCUCGACGGGCCCCGUGAG 22 7325

SCNNlA-3477 + ACGGGCUCGACGGGCCCCGUGAG 23 7326

SCNNlA-3478 + UACGGGCUCGACGGGCCCCGUGAG 24 7327

SCNNlA-3479 + AGGGUGACCAUCUGUGAG 18 7328

SCNNlA-3480 + GAGGGUGACCAUCUGUGAG 19 7329

SCNNlA-1141 + GGAGGGUGACCAUCUGUGAG 20 4990

SCNNlA-3481 + AGGAGGGUGACCAUCUGUGAG 21 7330

SCNNlA-3482 + CAGGAGGGUGACCAUCUGUGAG 22 7331

SCNNlA-3483 + ACAGGAGGGUGACCAUCUGUGAG 23 7332

SCNNlA-3484 + GACAGGAGGGUGACCAUCUGUGAG 24 7333

SCNNlA-3485 + GACAGGAUGUUGAUGUAG 18 7334

SCNNlA-3486 + CGACAGGAUGUUGAUGUAG 19 7335

SCNNlA-1143 + UCGACAGGAUGUUGAUGUAG 20 4992

SCNNlA-3487 + CUCGACAGGAUGUUGAUGUAG 21 7336

SCNNlA-3488 + CCUCGACAGGAUGUUGAUGUAG 22 7337

SCNNlA-3489 + GCCUCGACAGGAUGUUGAUGUAG 23 7338

SCNNlA-3490 + AGCCUCGACAGGAUGUUGAUGUAG 24 7339

1276

5535.1 SCNNlA-3491 + AGCUGGUAGCUGGUCACG 18 7340

SCNNlA-3492 + GAGCUGGUAGCUGGUCACG 19 7341

SCNNlA-3493 + AGAGCUGGUAGCUGGUCACG 20 7342

SCNNlA-3494 + GAGAGCUGGUAGCUGGUCACG 21 7343

SCNNlA-3495 + AGAGAGCUGGUAGCUGGUCACG 22 7344

SCNNlA-3496 + CAGAGAGCUGGUAGCUGGUCACG 23 7345

SCNNlA-3497 + GCAGAGAGCUGGUAGCUGGUCACG 24 7346

SCNNlA-3498 + AGGAGAGGUACAUUGACG 18 7347

SCNNlA-3499 + GAGGAGAGGUACAUUGACG 19 7348

SCNNlA-3500 + AGAGGAGAGGUACAUUGACG 20 7349

SCNNlA-3501 + GAGAGGAGAGGUACAUUGACG 21 7350

SCNNlA-3502 + UGAGAGGAGAGGUACAUUGACG 22 7351

SCNNlA-3503 + GUGAGAGGAGAGGUACAUUGACG 23 7352

SCNNlA-3504 + UGUGAGAGGAGAGGUACAUUGACG 24

7353

SCNNlA-3505 + CCACCACAGACAACACCG 18 7354

SCNNlA-3506 + UCCACCACAGACAACACCG 19 7355

SCNNlA-1146 + CUCCACCACAGACAACACCG 20 4995

SCNNlA-3507 + UCUCCACCACAGACAACACCG 21 7356

SCNNlA-3508 + AUCUCCACCACAGACAACACCG 22 7357

SCNNlA-3509 + CAUCUCCACCACAGACAACACCG 23 7358

SCNNlA-3510 + CCAUCUCCACCACAGACAACACCG 24 7359

SCNNlA-3511 + CGGGUACCUGAAGGGGCG 18 7360

SCNNlA-3512 + CCGGGUACCUGAAGGGGCG 19 7361

SCNNlA-1155 + UCCGGGUACCUGAAGGGGCG 20 5004

SCNNlA-3513 + UUCCGGGUACCUGAAGGGGCG 21 7362

SCNNlA-3514 + UUUCCGGGUACCUGAAGGGGCG 22 7363

SCNNlA-3515 + AUUUCCGGGUACCUGAAGGGGCG 23 7364

SCNNlA-3516 + AAUUUCCGGGUACCUGAAGGGGCG 24 7365

SCNNlA-3517 + GGCCACGCUACGGGCUCG 18 7366

SCNNlA-3518 + AGGCCACGCUACGGGCUCG 19 7367

SCNNlA-3519 + GAGGCCACGCUACGGGCUCG 20 7368

SCNNlA-3520 + GGAGGCCACGCUACGGGCUCG 21 7369

SCNNlA-3521 + UGGAGGCCACGCUACGGGCUCG 22 7370

SCNNlA-3522 + CUGGAGGCCACGCUACGGGCUCG 23 7371

SCNNlA-3523 + GCUGGAGGCCACGCUACGGGCUCG 24 7372

SCNNlA-3524 + GGGGAGGGGCUGUCAAGG 18 7373

SCNNlA-3525 + GGGGGAGGGGCUGUCAAGG 19 7374

SCNNlA-3526 + AGGGGGAGGGGCUGUCAAGG 20 7375

SCNNlA-3527 + CAGGGGGAGGGGCUGUCAAGG 21 7376

SCNNlA-3528 + GCAGGGGGAGGGGCUGUCAAGG 22 7377

SCNNlA-3529 + GGCAGGGGGAGGGGCUGUCAAGG 23 7378

1277

5535.1 SCNNlA-3530 + AGGCAGGGGGAGGGGCUGUCAAGG 24

7379

SCNNlA-3531 + GGGGCAGAAGUGGGAAGG 18 7380

SCNNlA-3532 + GGGGGCAGAAGUGGGAAGG 19 7381

SCNNlA-1161 + UGGGGGCAGAAGUGGGAAGG 20 5010

SCNNlA-3533 + GUGGGGGCAGAAGUGGGAAGG 21 7382

SCNNlA-3534 + GGUGGGGGCAGAAGUGGGAAGG 22 7383

SCNNlA-3535 + GGGUGGGGGCAGAAGUGGGAAGG 23 7384

SCNNlA-3536 + GGGGUGGGGGCAGAAGUGGGAAGG 24

7385

SCNNlA-3537 + GAAUACACACCUGGAAGG 18 7386

SCNNlA-3538 + UGAAUACACACCUGGAAGG 19 7387

SCNNlA-3539 + GUGAAUACACACCUGGAAGG 20 7388

SCNNlA-3540 + AGUGAAUACACACCUGGAAGG 21 7389

SCNNlA-3541 + GAGUGAAUACACACCUGGAAGG 22 7390

SCNNlA-3542 + GGAGUGAAUACACACCUGGAAGG 23 7391

SCNNlA-3543 + AGGAGUGAAUACACACCUGGAAGG 24 7392

SCNNlA-3544 + GCCCCCCCAGAGGACAGG 18 7393

SCNNlA-3545 + GGCCCCCCCAGAGGACAGG 19 7394

SCNNlA-1162 + GGGCCCCCCCAGAGGACAGG 20 5011

SCNNlA-3546 + AGGGCCCCCCCAGAGGACAGG 21 7395

SCNNlA-3547 + CAGGGCCCCCCCAGAGGACAGG 22 7396

SCNNlA-3548 + UCAGGGCCCCCCCAGAGGACAGG 23 7397

SCNNlA-3549 + CUCAGGGCCCCCCCAGAGGACAGG 24 7398

SCNNlA-3550 + CUCCACUGGCUGCCCAGG 18 7399

SCNNlA-3551 + GCUCCACUGGCUGCCCAGG 19 7400

SCNNlA-3552 + GGCUCCACUGGCUGCCCAGG 20 7401

SCNNlA-3553 + AGGCUCCACUGGCUGCCCAGG 21 7402

SCNNlA-3554 + CAGGCUCCACUGGCUGCCCAGG 22 7403

SCNNlA-3555 + ACAGGCUCCACUGGCUGCCCAGG 23 7404

SCNNlA-3556 + CACAGGCUCCACUGGCUGCCCAGG 24 7405

SCNNlA-3557 + GGAGGGGAGGAUGCCAGG 18 7406

SCNNlA-3558 + AGGAGGGGAGGAUGCCAGG 19 7407

SCNNlA-3559 + AAGGAGGGGAGGAUGCCAGG 20 7408

SCNNlA-3560 + GAAGGAGGGGAGGAUGCCAGG 21 7409

SCNNlA-3561 + GGAAGGAGGGGAGGAUGCCAGG 22 7410

SCNNlA-3562 + GGGAAGGAGGGGAGGAUGCCAGG 23 7411

SCNNlA-3563 + UGGGAAGGAGGGGAGGAUGCCAGG 24

7412

SCNNlA-3564 + CAGGGUGGCAUAGGCAGG 18 7413

SCNNlA-3565 + CCAGGGUGGCAUAGGCAGG 19 7414

SCNNlA-1167 + CCCAGGGUGGCAUAGGCAGG 20 5016

1278

5535.1 SCNNlA-3566 + GCCCAGGGUGGCAUAGGCAGG 21 7415

SCNNlA-3567 + GGCCCAGGGUGGCAUAGGCAGG 22 7416

SCNNlA-3568 + GGGCCCAGGGUGGCAUAGGCAGG 23 7417

SCNNlA-3569 + GGGGCCCAGGGUGGCAUAGGCAGG 24 7418

SCNNlA-3570 + AUGGAAGACAUCCAGAGG 18 7419

SCNNlA-3571 + CAUGGAAGACAUCCAGAGG 19 7420

SCNNlA-3572 + GCAUGGAAGACAUCCAGAGG 20 7421

SCNNlA-3573 + GGCAUGGAAGACAUCCAGAGG 21 7422

SCNNlA-3574 + AGGCAUGGAAGACAUCCAGAGG 22 7423

SCNNlA-3575 + CAGGCAUGGAAGACAUCCAGAGG 23 7424

SCNNlA-3576 + CCAGGCAUGGAAGACAUCCAGAGG 24 7425

SCNNlA-3577 + UUAGGUGUGGGGCAGAGG 18 7426

SCNNlA-3578 + CUUAGGUGUGGGGCAGAGG 19 7427

SCNNlA-3579 + UCUUAGGUGUGGGGCAGAGG 20 7428

SCNNlA-3580 + UUCUUAGGUGUGGGGCAGAGG 21 7429

SCNNlA-3581 + UUUCUUAGGUGUGGGGCAGAGG 22 7430

SCNNlA-3582 + AUUUCUUAGGUGUGGGGCAGAGG 23 7431

SCNNlA-3583 + CAUUUCUUAGGUGUGGGGCAGAGG 24

7432

SCNNlA-3584 + CACCUGGAAGGGAGGAGG 18 7433

SCNNlA-3585 + ACACCUGGAAGGGAGGAGG 19 7434

SCNNlA-3586 + CACACCUGGAAGGGAGGAGG 20 7435

SCNNlA-3587 + ACACACCUGGAAGGGAGGAGG 21 7436

SCNNlA-3588 + UACACACCUGGAAGGGAGGAGG 22 7437

SCNNlA-3589 + AUACACACCUGGAAGGGAGGAGG 23 7438

SCNNlA-3590 + AAUACACACCUGGAAGGGAGGAGG 24 7439

SCNNlA-3591 + UCGACGGGCCCCGUGAGG 18 7440

SCNNlA-3592 + CUCGACGGGCCCCGUGAGG 19 7441

SCNNlA-1172 + GCUCGACGGGCCCCGUGAGG 20 5021

SCNNlA-3593 + GGCUCGACGGGCCCCGUGAGG 21 7442

SCNNlA-3594 + GGGCUCGACGGGCCCCGUGAGG 22 7443

SCNNlA-3595 + CGGGCUCGACGGGCCCCGUGAGG 23 7444

SCNNlA-3596 + ACGGGCUCGACGGGCCCCGUGAGG 24 7445

SCNNlA-3597 + GGCCCAGGGUGGCAUAGG 18 7446

SCNNlA-3598 + GGGCCCAGGGUGGCAUAGG 19 7447

SCNNlA-3599 + GGGGCCCAGGGUGGCAUAGG 20 7448

SCNNlA-3600 + GGGGGCCCAGGGUGGCAUAGG 21 7449

SCNNlA-3601 + CGGGGGCCCAGGGUGGCAUAGG 22 7450

SCNNlA-3602 + GCGGGGGCCCAGGGUGGCAUAGG 23 7451

SCNNlA-3603 + GGCGGGGGCCCAGGGUGGCAUAGG 24 7452

SCNNlA-3604 + AAUACACACCUGGAAGGG 18 7453

SCNNlA-3605 + GAAUACACACCUGGAAGGG 19 7454

1279

5535.1 SCNNlA-1176 + UGAAUACACACCUGGAAGGG 20 5025

SCNNlA-3606 + GUGAAUACACACCUGGAAGGG 21 7455

SCNNlA-3607 + AGUGAAUACACACCUGGAAGGG 22 7456

SCNNlA-3608 + GAGUGAAUACACACCUGGAAGGG 23 7457

SCNNlA-3609 + GGAGUGAAUACACACCUGGAAGGG 24 7458

SCNNlA-3610 + UUCCGGGUACCUGAAGGG 18 7459

SCNNlA-3611 + UUUCCGGGUACCUGAAGGG 19 7460

SCNNlA-3612 + AUUUCCGGGUACCUGAAGGG 20 7461

SCNNlA-3613 + AAUUUCCGGGUACCUGAAGGG 21 7462

SCNNlA-3614 + UAAUUUCCGGGUACCUGAAGGG 22 7463

SCNNlA-3615 + UUAAUUUCCGGGUACCUGAAGGG 23 7464

SCNNlA-3616 + UUUAAUUUCCGGGUACCUGAAGGG 24 7465

SCNNlA-3617 + UUGUGGCUGGGACCAGGG 18 7466

SCNNlA-3618 + CUUGUGGCUGGGACCAGGG 19 7467

SCNNlA-3619 + UCUUGUGGCUGGGACCAGGG 20 7468

SCNNlA-3620 + GAGGGGAGGAUGCCAGGG 18 7469

SCNNlA-3621 + GGAGGGGAGGAUGCCAGGG 19 7470

SCNNlA-1178 + AGGAGGGGAGGAUGCCAGGG 20 5027

SCNNlA-3622 + AAGGAGGGGAGGAUGCCAGGG 21 7471

SCNNlA-3623 + GAAGGAGGGGAGGAUGCCAGGG 22 7472

SCNNlA-3624 + GGAAGGAGGGGAGGAUGCCAGGG 23 7473

SCNNlA-3625 + GGGAAGGAGGGGAGGAUGCCAGGG 24

7474

SCNNlA-3626 + UAGGUGUGGGGCAGAGGG 18 7475

SCNNlA-3627 + UUAGGUGUGGGGCAGAGGG 19 7476

SCNNlA-1179 + CUUAGGUGUGGGGCAGAGGG 20 5028

SCNNlA-3628 + UCUUAGGUGUGGGGCAGAGGG 21 7477

SCNNlA-3629 + UUCUUAGGUGUGGGGCAGAGGG 22 7478

SCNNlA-3630 + UUUCUUAGGUGUGGGGCAGAGGG 23 7479

SCNNlA-3631 + AUUUCUUAGGUGUGGGGCAGAGGG 24

7480

SCNNlA-3632 + ACCUGGAAGGGAGGAGGG 18 7481

SCNNlA-3633 + CACCUGGAAGGGAGGAGGG 19 7482

SCNNlA-1180 + ACACCUGGAAGGGAGGAGGG 20 5029

SCNNlA-3634 + CACACCUGGAAGGGAGGAGGG 21 7483

SCNNlA-3635 + ACACACCUGGAAGGGAGGAGGG 22 7484

SCNNlA-3636 + UACACACCUGGAAGGGAGGAGGG 23 7485

SCNNlA-3637 + AUACACACCUGGAAGGGAGGAGGG 24 7486

SCNNlA-3638 + GGGUGGCAUAGGCAGGGG 18 7487

SCNNlA-3639 + AGGGUGGCAUAGGCAGGGG 19 7488

SCNNlA-3640 + CAGGGUGGCAUAGGCAGGGG 20 7489

SCNNlA-3641 + CCAGGGUGGCAUAGGCAGGGG 21 7490

1280

5535.1 SCNNlA-3642 + CCCAGGGUGGCAUAGGCAGGGG 22 7491

SCNNlA-3643 + GCCCAGGGUGGCAUAGGCAGGGG 23 7492

SCNNlA-3644 + GGCCCAGGGUGGCAUAGGCAGGGG 24 7493

SCNNlA-3645 + ACCUGAAGGGGCGAGGGG 18 7494

SCNNlA-3646 + UACCUGAAGGGGCGAGGGG 19 7495

SCNNlA-3647 + GUACCUGAAGGGGCGAGGGG 20 7496

SCNNlA-3648 + GGUACCUGAAGGGGCGAGGGG 21 7497

SCNNlA-3649 + GGGUACCUGAAGGGGCGAGGGG 22 7498

SCNNlA-3650 + CGGGUACCUGAAGGGGCGAGGGG 23 7499

SCNNlA-3651 + CCGGGUACCUGAAGGGGCGAGGGG 24 7500

SCNNlA-3652 + GGGCCCCGUGAGGCGGGG 18 7501

SCNNlA-3653 + CGGGCCCCGUGAGGCGGGG 19 7502

SCNNlA-3654 + ACGGGCCCCGUGAGGCGGGG 20 7503

SCNNlA-3655 + GACGGGCCCCGUGAGGCGGGG 21 7504

SCNNlA-3656 + CGACGGGCCCCGUGAGGCGGGG 22 7505

SCNNlA-3657 + UCGACGGGCCCCGUGAGGCGGGG 23 7506

SCNNlA-3658 + CUCGACGGGCCCCGUGAGGCGGGG 24 7507

SCNNlA-3659 + GGUGGCAUAGGCAGGGGG 18 7508

SCNNlA-3660 + GGGUGGCAUAGGCAGGGGG 19 7509

SCNNlA-1184 + AGGGUGGCAUAGGCAGGGGG 20 5033

SCNNlA-3661 + CAGGGUGGCAUAGGCAGGGGG 21 7510

SCNNlA-3662 + CCAGGGUGGCAUAGGCAGGGGG 22 7511

SCNNlA-3663 + CCCAGGGUGGCAUAGGCAGGGGG 23 7512

SCNNlA-3664 + GCCCAGGGUGGCAUAGGCAGGGGG 24 7513

SCNNlA-3665 + GGCCCCGUGAGGCGGGGG 18 7514

SCNNlA-3666 + GGGCCCCGUGAGGCGGGGG 19 7515

SCNNlA-1185 + CGGGCCCCGUGAGGCGGGGG 20 5034

SCNNlA-3667 + ACGGGCCCCGUGAGGCGGGGG 21 7516

SCNNlA-3668 + GACGGGCCCCGUGAGGCGGGGG 22 7517

SCNNlA-3669 + CGACGGGCCCCGUGAGGCGGGGG 23 7518

SCNNlA-3670 + UCGACGGGCCCCGUGAGGCGGGGG 24 7519

SCNNlA-3671 + AGAGACAUGGGGUGGGGG 18 7520

SCNNlA-3672 + CAGAGACAUGGGGUGGGGG 19 7521

SCNNlA-3673 + ACAGAGACAUGGGGUGGGGG 20 7522

SCNNlA-3674 + GACAGAGACAUGGGGUGGGGG 21 7523

SCNNlA-3675 + GGACAGAGACAUGGGGUGGGGG 22 7524

SCNNlA-3676 + AGGACAGAGACAUGGGGUGGGGG 23 7525

SCNNlA-3677 + AAGGACAGAGACAUGGGGUGGGGG 24

7526

SCNNlA-3678 + AAGGACAGAGACAUGGGG 18 7527

SCNNlA-3679 + CAAGGACAGAGACAUGGGG 19 7528

SCNNlA-1186 + ACAAGGACAGAGACAUGGGG 20 5035

1281

5535.1 SCNNlA-3680 + GACAAGGACAGAGACAUGGGG 21 7529

SCNNlA-3681 + GGACAAGGACAGAGACAUGGGG 22 7530

SCNNlA-3682 + GGGACAAGGACAGAGACAUGGGG 23 7531

SCNNlA-3683 + UGGGACAAGGACAGAGACAUGGGG 24 7532

SCNNlA-3684 + UAGCUGGUCACGCUGGGG 18 7533

SCNNlA-3685 + GUAGCUGGUCACGCUGGGG 19 7534

SCNNlA-3686 + GGUAGCUGGUCACGCUGGGG 20 7535

SCNNlA-3687 + UGGUAGCUGGUCACGCUGGGG 21 7536

SCNNlA-3688 + CUGGUAGCUGGUCACGCUGGGG 22 7537

SCNNlA-3689 + GCUGGUAGCUGGUCACGCUGGGG 23 7538

SCNNlA-3690 + AGCUGGUAGCUGGUCACGCUGGGG 24 7539

SCNNlA-3691 + CAUUUCUUAGGUGUGGGG 18 7540

SCNNlA-3692 + CCAUUUCUUAGGUGUGGGG 19 7541

SCNNlA-3693 + UCCAUUUCUUAGGUGUGGGG 20 7542

SCNNlA-3694 + CUCCAUUUCUUAGGUGUGGGG 21 7543

SCNNlA-3695 + ACUCCAUUUCUUAGGUGUGGGG 22 7544

SCNNlA-3696 + CACUCCAUUUCUUAGGUGUGGGG 23 7545

SCNNlA-3697 + CCACUCCAUUUCUUAGGUGUGGGG 24 7546

SCNNlA-3698 + CAAGGACAGAGACAUGGG 18 7547

SCNNlA-3699 + ACAAGGACAGAGACAUGGG 19 7548

SCNNlA-3700 + GACAAGGACAGAGACAUGGG 20 7549

SCNNlA-3701 + GGACAAGGACAGAGACAUGGG 21 7550

SCNNlA-3702 + GGGACAAGGACAGAGACAUGGG 22 7551

SCNNlA-3703 + UGGGACAAGGACAGAGACAUGGG 23 7552

SCNNlA-3704 + CUGGGACAAGGACAGAGACAUGGG 24 7553

SCNNlA-3705 + GAGCCCCCUGGAGAUGGG 18 7554

SCNNlA-3706 + AGAGCCCCCUGGAGAUGGG 19 7555

SCNNlA-1188 + CAGAGCCCCCUGGAGAUGGG 20 5037

SCNNlA-3707 + GCAGAGCCCCCUGGAGAUGGG 21 7556

SCNNlA-3708 + UGCAGAGCCCCCUGGAGAUGGG 22 7557

SCNNlA-3709 + CUGCAGAGCCCCCUGGAGAUGGG 23 7558

SCNNlA-3710 + CCUGCAGAGCCCCCUGGAGAUGGG 24 7559

SCNNlA-3711 + GGUGGGGGCAGAAGUGGG 18 7560

SCNNlA-3712 + GGGUGGGGGCAGAAGUGGG 19 7561

SCNNlA-3713 + GGGGUGGGGGCAGAAGUGGG 20 7562

SCNNlA-3714 + UGGGGUGGGGGCAGAAGUGGG 21 7563

SCNNlA-3715 + AUGGGGUGGGGGCAGAAGUGGG 22 7564

SCNNlA-3716 + CAUGGGGUGGGGGCAGAAGUGGG 23 7565

SCNNlA-3717 + ACAUGGGGUGGGGGCAGAAGUGGG 24

7566

SCNNlA-3718 + UGUGGGGCAGAGGGUGGG 18 7567

SCNNlA-3719 + GUGUGGGGCAGAGGGUGGG 19 7568

1282

5535.1 SCNNlA-3720 + GGUGUGGGGCAGAGGGUGGG 20 7569

SCNNlA-3721 + AGGUGUGGGGCAGAGGGUGGG 21 7570

SCNNlA-3722 + UAGGUGUGGGGCAGAGGGUGGG 22 7571

SCNNlA-3723 + UUAGGUGUGGGGCAGAGGGUGGG 23 7572

SCNNlA-3724 + CUUAGGUGUGGGGCAGAGGGUGGG 24

7573

SCNNlA-3725 + AGAGCCCCCUGGAGAUGG 18 7574

SCNNlA-3726 + CAGAGCCCCCUGGAGAUGG 19 7575

SCNNlA-3727 + GCAGAGCCCCCUGGAGAUGG 20 7576

SCNNlA-3728 + UGCAGAGCCCCCUGGAGAUGG 21 7577

SCNNlA-3729 + CUGCAGAGCCCCCUGGAGAUGG 22 7578

SCNNlA-3730 + CCUGCAGAGCCCCCUGGAGAUGG 23 7579

SCNNlA-3731 + CCCUGCAGAGCCCCCUGGAGAUGG 24 7580

SCNNlA-3732 + GAGUGAAUACACACCUGG 18 7581

SCNNlA-3733 + GGAGUGAAUACACACCUGG 19 7582

SCNNlA-3734 + AGGAGUGAAUACACACCUGG 20 7583

SCNNlA-3735 + CAGGAGUGAAUACACACCUGG 21 7584

SCNNlA-3736 + GCAGGAGUGAAUACACACCUGG 22 7585

SCNNlA-3737 + AGCAGGAGUGAAUACACACCUGG 23 7586

SCNNlA-3738 + AAGCAGGAGUGAAUACACACCUGG 24 7587

SCNNlA-3739 + UGGUUGCAGGAGACCUGG 18 7588

SCNNlA-3740 + CUGGUUGCAGGAGACCUGG 19 7589

SCNNlA-3741 + CCUGGUUGCAGGAGACCUGG 20 7590

SCNNlA-3742 + GCCUGGUUGCAGGAGACCUGG 21 7591

SCNNlA-3743 + CGCCUGGUUGCAGGAGACCUGG 22 7592

SCNNlA-3744 + ACGCCUGGUUGCAGGAGACCUGG 23 7593

SCNNlA-3745 + CACGCCUGGUUGCAGGAGACCUGG 24 7594

SCNNlA-3746 + AGAGGGAGCAGGGCCUGG 18 7595

SCNNlA-3747 + GAGAGGGAGCAGGGCCUGG 19 7596

SCNNlA-3748 + GGAGAGGGAGCAGGGCCUGG 20 7597

SCNNlA-3749 + UGGAGAGGGAGCAGGGCCUGG 21 7598

SCNNlA-3750 + CUGGAGAGGGAGCAGGGCCUGG 22 7599

SCNNlA-3751 + GCUGGAGAGGGAGCAGGGCCUGG 23 7600

SCNNlA-3752 + GGCUGGAGAGGGAGCAGGGCCUGG 24 7601

SCNNlA-3753 + CCUGAUGAGUAUGUCUGG 18 7602

SCNNlA-3754 + CCCUGAUGAGUAUGUCUGG 19 7603

SCNNlA-3755 + CCCCUGAUGAGUAUGUCUGG 20 7604

SCNNlA-3756 + ACCCCUGAUGAGUAUGUCUGG 21 7605

SCNNlA-3757 + CACCCCUGAUGAGUAUGUCUGG 22 7606

SCNNlA-3758 + CCACCCCUGAUGAGUAUGUCUGG 23 7607

SCNNlA-3759 + UCCACCCCUGAUGAGUAUGUCUGG 24 7608

SCNNlA-3760 + CCCCCAGAGGACAGGUGG 18 7609

1283

5535.1 SCNNlA-3761 + CCCCCCAGAGGACAGGUGG 19 7610

SCNNlA-1200 + CCCCCCCAGAGGACAGGUGG 20 5049

SCNNlA-3762 + GCCCCCCCAGAGGACAGGUGG 21 7611

SCNNlA-3763 + GGCCCCCCCAGAGGACAGGUGG 22 7612

SCNNlA-3764 + GGGCCCCCCCAGAGGACAGGUGG 23 7613

SCNNlA-3765 + AGGGCCCCCCCAGAGGACAGGUGG 24 7614

SCNNlA-3766 + UUUCCAUACAUCGGGUGG 18 7615

SCNNlA-3767 + GUUUCCAUACAUCGGGUGG 19 7616

SCNNlA-1202 + AGUUUCCAUACAUCGGGUGG 20 5051

SCNNlA-3768 + CAGUUUCCAUACAUCGGGUGG 21 7617

SCNNlA-3769 + GCAGUUUCCAUACAUCGGGUGG 22 7618

SCNNlA-3770 + AGCAGUUUCCAUACAUCGGGUGG 23 7619

SCNNlA-3771 + UAGCAGUUUCCAUACAUCGGGUGG 24 7620

SCNNlA-3772 + AACCUUCGGAGCAGCAUG 18 7621

SCNNlA-3773 + GAACCUUCGGAGCAGCAUG 19 7622

SCNNlA-1209 + GGAACCUUCGGAGCAGCAUG 20 5058

SCNNlA-3774 + CGGAACCUUCGGAGCAGCAUG 21 7623

SCNNlA-3775 + UCGGAACCUUCGGAGCAGCAUG 22 7624

SCNNlA-3776 + UUCGGAACCUUCGGAGCAGCAUG 23 7625

SCNNlA-3777 + CUUCGGAACCUUCGGAGCAGCAUG 24 7626

SCNNlA-3778 + CUGGUCACGCUGGGGAUG 18 7627

SCNNlA-3779 + GCUGGUCACGCUGGGGAUG 19 7628

SCNNlA-3780 + AGCUGGUCACGCUGGGGAUG 20 7629

SCNNlA-3781 + UAGCUGGUCACGCUGGGGAUG 21 7630

SCNNlA-3782 + GUAGCUGGUCACGCUGGGGAUG 22 7631

SCNNlA-3783 + GGUAGCUGGUCACGCUGGGGAUG 23 7632

SCNNlA-3784 + UGGUAGCUGGUCACGCUGGGGAUG 24

7633

SCNNlA-3785 + UUAAUUUCCGGGUACCUG 18 7634

SCNNlA-3786 + UUUAAUUUCCGGGUACCUG 19 7635

SCNNlA-3787 + CUUUAAUUUCCGGGUACCUG 20 7636

SCNNlA-3788 + UCUUUAAUUUCCGGGUACCUG 21 7637

SCNNlA-3789 + CUCUUUAAUUUCCGGGUACCUG 22 7638

SCNNlA-3790 + CCUCUUUAAUUUCCGGGUACCUG 23 7639

SCNNlA-3791 + UCCUCUUUAAUUUCCGGGUACCUG 24 7640

SCNNlA-3792 + UGGAGGAACUGGCCCCUG 18 7641

SCNNlA-3793 + GUGGAGGAACUGGCCCCUG 19 7642

SCNNlA-3794 + GGUGGAGGAACUGGCCCCUG 20 7643

SCNNlA-3795 + AGGUGGAGGAACUGGCCCCUG 21 7644

SCNNlA-3796 + CAGGUGGAGGAACUGGCCCCUG 22 7645

SCNNlA-3797 + ACAGGUGGAGGAACUGGCCCCUG 23 7646

SCNNlA-3798 + GACAGGUGGAGGAACUGGCCCCUG 24 7647

1284

5535.1 SCNNlA-3799 + GAGGGGCUGUCAAGGCUG 18 7648

SCNNlA-3800 + GGAGGGGCUGUCAAGGCUG 19 7649

SCNNlA-3801 + GGGAGGGGCUGUCAAGGCUG 20 7650

SCNNlA-3802 + GGGGAGGGGCUGUCAAGGCUG 21 7651

SCNNlA-3803 + GGGGGAGGGGCUGUCAAGGCUG 22 7652

SCNNlA-3804 + AGGGGGAGGGGCUGUCAAGGCUG 23 7653

SCNNlA-3805 + CAGGGGGAGGGGCUGUCAAGGCUG 24 7654

SCNNlA-3806 + CGCAGGUCGCGACGGCUG 18 7655

SCNNlA-3807 + CCGCAGGUCGCGACGGCUG 19 7656

SCNNlA-1223 + CCCGCAGGUCGCGACGGCUG 20 5072

SCNNlA-3808 + CCCCGCAGGUCGCGACGGCUG 21 7657

SCNNlA-3809 + CCCCCGCAGGUCGCGACGGCUG 22 7658

SCNNlA-3810 + UCCCCCGCAGGUCGCGACGGCUG 23 7659

SCNNlA-3811 + GUCCCCCGCAGGUCGCGACGGCUG 24 7660

SCNNlA-3812 + CUUGCCUUCCUCAUGCUG 18 7661

SCNNlA-3813 + CCUUGCCUUCCUCAUGCUG 19 7662

SCNNlA-3814 + UCCUUGCCUUCCUCAUGCUG 20 7663

SCNNlA-3815 + AUCCUUGCCUUCCUCAUGCUG 21 7664

SCNNlA-3816 + CAUCCUUGCCUUCCUCAUGCUG 22 7665

SCNNlA-3817 + GCAUCCUUGCCUUCCUCAUGCUG 23 7666

SCNNlA-3818 + AGCAUCCUUGCCUUCCUCAUGCUG 24 7667

SCNNlA-3819 + AACAGCCCAGGUGGUCUG 18 7668

SCNNlA-3820 + AAACAGCCCAGGUGGUCUG 19 7669

SCNNlA-1225 + GAAACAGCCCAGGUGGUCUG 20 5074

SCNNlA-3821 + UGAAACAGCCCAGGUGGUCUG 21 7670

SCNNlA-3822 + GUGAAACAGCCCAGGUGGUCUG 22 7671

SCNNlA-3823 + GGUGAAACAGCCCAGGUGGUCUG 23 7672

SCNNlA-3824 + UGGUGAAACAGCCCAGGUGGUCUG 24 7673

SCNNlA-3825 + GAGCCGGCCACGAGAGUG 18 7674

SCNNlA-3826 + GGAGCCGGCCACGAGAGUG 19 7675

SCNNlA-3827 + GGGAGCCGGCCACGAGAGUG 20 7676

SCNNlA-3828 + CGGGAGCCGGCCACGAGAGUG 21 7677

SCNNlA-3829 + GCGGGAGCCGGCCACGAGAGUG 22 7678

SCNNlA-3830 + UGCGGGAGCCGGCCACGAGAGUG 23 7679

SCNNlA-3831 + CUGCGGGAGCCGGCCACGAGAGUG 24 7680

SCNNlA-3832 + CCCCCCAGAGGACAGGUG 18 7681

SCNNlA-3833 + CCCCCCCAGAGGACAGGUG 19 7682

SCNNlA-3834 + GCCCCCCCAGAGGACAGGUG 20 7683

SCNNlA-3835 + GGCCCCCCCAGAGGACAGGUG 21 7684

SCNNlA-3836 + GGGCCCCCCCAGAGGACAGGUG 22 7685

SCNNlA-3837 + AGGGCCCCCCCAGAGGACAGGUG 23 7686

SCNNlA-3838 + CAGGGCCCCCCCAGAGGACAGGUG 24 7687

1285

5535.1 SCNNlA-3839 + CACUCCAUUUCUUAGGUG 18 7688

SCNNlA-3840 + CCACUCCAUUUCUUAGGUG 19 7689

SCNNlA-1232 + GCCACUCCAUUUCUUAGGUG 20 5081

SCNNlA-3841 + GGCCACUCCAUUUCUUAGGUG 21 7690

SCNNlA-3842 + UGGCCACUCCAUUUCUUAGGUG 22 7691

SCNNlA-3843 + UUGGCCACUCCAUUUCUUAGGUG 23 7692

SCNNlA-3844 + UUUGGCCACUCCAUUUCUUAGGUG 24 7693

SCNNlA-3845 + CUGGAAGGGAGGAGGGUG 18 7694

SCNNlA-3846 + CCUGGAAGGGAGGAGGGUG 19 7695

SCNNlA-3847 + ACCUGGAAGGGAGGAGGGUG 20 7696

SCNNlA-3848 + CACCUGGAAGGGAGGAGGGUG 21 7697

SCNNlA-3849 + ACACCUGGAAGGGAGGAGGGUG 22 7698

SCNNlA-3850 + CACACCUGGAAGGGAGGAGGGUG 23 7699

SCNNlA-3851 + ACACACCUGGAAGGGAGGAGGGUG 24 7700

SCNNlA-3852 + GUUUCCAUACAUCGGGUG 18 7701

SCNNlA-3853 + AGUUUCCAUACAUCGGGUG 19 7702

SCNNlA-3854 + CAGUUUCCAUACAUCGGGUG 20 7703

SCNNlA-3855 + GCAGUUUCCAUACAUCGGGUG 21 7704

SCNNlA-3856 + AGCAGUUUCCAUACAUCGGGUG 22 7705

SCNNlA-3857 + UAGCAGUUUCCAUACAUCGGGUG 23 7706

SCNNlA-3858 + AUAGCAGUUUCCAUACAUCGGGUG 24 7707

SCNNlA-3859 + GGGACAGACCUAGGGGUG 18 7708

SCNNlA-3860 + AGGGACAGACCUAGGGGUG 19 7709

SCNNlA-3861 + CAGGGACAGACCUAGGGGUG 20 7710

SCNNlA-3862 + UCAGGGACAGACCUAGGGGUG 21 7711

SCNNlA-3863 + AUCAGGGACAGACCUAGGGGUG 22 7712

SCNNlA-3864 + CAUCAGGGACAGACCUAGGGGUG 23 7713

SCNNlA-3865 + GCAUCAGGGACAGACCUAGGGGUG 24 7714

SCNNlA-3866 + CCGGCCACGAGAGUGGUG 18 7715

SCNNlA-3867 + GCCGGCCACGAGAGUGGUG 19 7716

SCNNlA-3868 + AGCCGGCCACGAGAGUGGUG 20 7717

SCNNlA-3869 + GAGCCGGCCACGAGAGUGGUG 21 7718

SCNNlA-3870 + GGAGCCGGCCACGAGAGUGGUG 22 7719

SCNNlA-3871 + GGGAGCCGGCCACGAGAGUGGUG 23 7720

SCNNlA-3872 + CGGGAGCCGGCCACGAGAGUGGUG 24 7721

SCNNlA-3873 + CAUGGCUUCCGGCACUUG 18 7722

SCNNlA-3874 + GCAUGGCUUCCGGCACUUG 19 7723

SCNNlA-3875 + UGCAUGGCUUCCGGCACUUG 20 7724

SCNNlA-3876 + CUGCAUGGCUUCCGGCACUUG 21 7725

SCNNlA-3877 + CCUGCAUGGCUUCCGGCACUUG 22 7726

SCNNlA-3878 + ACCUGCAUGGCUUCCGGCACUUG 23 7727

SCNNlA-3879 + AACCUGCAUGGCUUCCGGCACUUG 24 7728

1286

5535.1 SCNNlA-3880 + UUGUAGUUCAGCUCCUUG 18 7729

SCNNlA-3881 + UUUGUAGUUCAGCUCCUUG 19 7730

SCNNlA-3882 + UUUUGUAGUUCAGCUCCUUG 20 7731

SCNNlA-3883 + GUUUUGUAGUUCAGCUCCUUG 21 7732

SCNNlA-3884 + GGUUUUGUAGUUCAGCUCCUUG 22 7733

SCNNlA-3885 + UGGUUUUGUAGUUCAGCUCCUUG 23 7734

SCNNlA-3886 + UUGGUUUUGUAGUUCAGCUCCUUG 24

7735

SCNNlA-3887 + CUGACUCACGCCUGGUUG 18 7736

SCNNlA-3888 + ACUGACUCACGCCUGGUUG 19 7737

SCNNlA-3889 + GACUGACUCACGCCUGGUUG 20 7738

SCNNlA-3890 + GGACUGACUCACGCCUGGUUG 21 7739

SCNNlA-3891 + AGGACUGACUCACGCCUGGUUG 22 7740

SCNNlA-3892 + CAGGACUGACUCACGCCUGGUUG 23 7741

SCNNlA-3893 + GCAGGACUGACUCACGCCUGGUUG 24 7742

SCNNlA-3894 + GAACCUUCGGAGCAGCAU 18 7743

SCNNlA-3895 + GGAACCUUCGGAGCAGCAU 19 7744

SCNNlA-3896 + CGGAACCUUCGGAGCAGCAU 20 7745

SCNNlA-3897 + UCGGAACCUUCGGAGCAGCAU 21 7746

SCNNlA-3898 + UUCGGAACCUUCGGAGCAGCAU 22 7747

SCNNlA-3899 + CUUCGGAACCUUCGGAGCAGCAU 23 7748

SCNNlA-3900 + GCUUCGGAACCUUCGGAGCAGCAU 24 7749

SCNNlA-3901 + CUGCUCUGCGCGCAGCAU 18 7750

SCNNlA-3902 + UCUGCUCUGCGCGCAGCAU 19 7751

SCNNlA-3903 + UUCUGCUCUGCGCGCAGCAU 20 7752

SCNNlA-3904 + AUUCUGCUCUGCGCGCAGCAU 21 7753

SCNNlA-3905 + CAUUCUGCUCUGCGCGCAGCAU 22 7754

SCNNlA-3906 + UCAUUCUGCUCUGCGCGCAGCAU 23 7755

SCNNlA-3907 + GUCAUUCUGCUCUGCGCGCAGCAU 24 7756

SCNNlA-3908 + GUUCUGUCGCGAUAGCAU 18 7757

SCNNlA-3909 + UGUUCUGUCGCGAUAGCAU 19 7758

SCNNlA-3910 + UUGUUCUGUCGCGAUAGCAU 20 7759

SCNNlA-3911 + AUUGUUCUGUCGCGAUAGCAU 21 7760

SCNNlA-3912 + AAUUGUUCUGUCGCGAUAGCAU 22 7761

SCNNlA-3913 + UAAUUGUUCUGUCGCGAUAGCAU 23 7762

SCNNlA-3914 + GUAAUUGUUCUGUCGCGAUAGCAU 24 7763

SCNNlA-3915 + GUGAGAGUAAUUCCUUAU 18 7764

SCNNlA-3916 + AGUGAGAGUAAUUCCUUAU 19 7765

SCNNlA-3917 + AAGUGAGAGUAAUUCCUUAU 20 7766

SCNNlA-3918 + GAAGUGAGAGUAAUUCCUUAU 21 7767

SCNNlA-3919 + GGAAGUGAGAGUAAUUCCUUAU 22 7768

SCNNlA-3920 + UGGAAGUGAGAGUAAUUCCUUAU 23 7769

1287

5535.1 SCNNlA-3921 + GUGGAAGUGAGAGUAAUUCCUUAU 24

7770

SCNNlA-3922 + ACCCGGGCCCCAGUCACU 18 7771

SCNNlA-3923 + UACCCGGGCCCCAGUCACU 19 7772

SCNNlA-3924 + UUACCCGGGCCCCAGUCACU 20 7773

SCNNlA-3925 + AUUACCCGGGCCCCAGUCACU 21 7774

SCNNlA-3926 + CAUUACCCGGGCCCCAGUCACU 22 7775

SCNNlA-3927 + CCAUUACCCGGGCCCCAGUCACU 23 7776

SCNNlA-3928 + ACCAUUACCCGGGCCCCAGUCACU 24 7777

SCNNlA-3929 + UCACCUGCUGUGUGUACU 18 7778

SCNNlA-3930 + CUCACCUGCUGUGUGUACU 19 7779

SCNNlA-3931 + CCUCACCUGCUGUGUGUACU 20 7780

SCNNlA-3932 + GCCUCACCUGCUGUGUGUACU 21 7781

SCNNlA-3933 + GGCCUCACCUGCUGUGUGUACU 22 7782

SCNNlA-3934 + GGGCCUCACCUGCUGUGUGUACU 23 7783

SCNNlA-3935 + UGGGCCUCACCUGCUGUGUGUACU 24 7784

SCNNlA-3936 + GUAUCGGCUUCGGAACCU 18 7785

SCNNlA-3937 + AGUAUCGGCUUCGGAACCU 19 7786

SCNNlA-3938 + CAGUAUCGGCUUCGGAACCU 20 7787

SCNNlA-3939 + CCAGUAUCGGCUUCGGAACCU 21 7788

SCNNlA-3940 + ACCAGUAUCGGCUUCGGAACCU 22 7789

SCNNlA-3941 + GACCAGUAUCGGCUUCGGAACCU 23 7790

SCNNlA-3942 + AGACCAGUAUCGGCUUCGGAACCU 24 7791

SCNNlA-3943 + UCUGGAAGACCCAUUCCU 18 7792

SCNNlA-3944 + AUCUGGAAGACCCAUUCCU 19 7793

SCNNlA-1270 + CAUCUGGAAGACCCAUUCCU 20 5119

SCNNlA-3945 + GCAUCUGGAAGACCCAUUCCU 21 7794

SCNNlA-3946 + AGCAUCUGGAAGACCCAUUCCU 22 7795

SCNNlA-3947 + UAGCAUCUGGAAGACCCAUUCCU 23 7796

SCNNlA-3948 + AUAGCAUCUGGAAGACCCAUUCCU 24 7797

SCNNlA-3949 + GUCUGUCCAGGGUUUCCU 18 7798

SCNNlA-3950 + AGUCUGUCCAGGGUUUCCU 19 7799

SCNNlA-3951 + AAGUCUGUCCAGGGUUUCCU 20 7800

SCNNlA-3952 + CAAGUCUGUCCAGGGUUUCCU 21 7801

SCNNlA-3953 + CCAAGUCUGUCCAGGGUUUCCU 22 7802

SCNNlA-3954 + CCCAAGUCUGUCCAGGGUUUCCU 23 7803

SCNNlA-3955 + CCCCAAGUCUGUCCAGGGUUUCCU 24 7804

SCNNlA-3956 + CAAGCUGGAGGCCACGCU 18 7805

SCNNlA-3957 + GCAAGCUGGAGGCCACGCU 19 7806

SCNNlA-3958 + CGCAAGCUGGAGGCCACGCU 20 7807

SCNNlA-3959 + CCGCAAGCUGGAGGCCACGCU 21 7808

SCNNlA-3960 + CCCGCAAGCUGGAGGCCACGCU 22 7809

1288

5535.1 SCNNlA-3961 + UCCCGCAAGCUGGAGGCCACGCU 23 7810

SCNNlA-3962 + GUCCCGCAAGCUGGAGGCCACGCU 24 7811

SCNNlA-3963 + CCGCAGGUCGCGACGGCU 18 7812

SCNNlA-3964 + CCCGCAGGUCGCGACGGCU 19 7813

SCNNlA-3965 + CCCCGCAGGUCGCGACGGCU 20 7814

SCNNlA-3966 + CCCCCGCAGGUCGCGACGGCU 21 7815

SCNNlA-3967 + UCCCCCGCAGGUCGCGACGGCU 22 7816

SCNNlA-3968 + GUCCCCCGCAGGUCGCGACGGCU 23 7817

SCNNlA-3969 + AGUCCCCCGCAGGUCGCGACGGCU 24 7818

SCNNlA-3970 + UGGAGACCAGUAUCGGCU 18 7819

SCNNlA-3971 + CUGGAGACCAGUAUCGGCU 19 7820

SCNNlA-3972 + CCUGGAGACCAGUAUCGGCU 20 7821

SCNNlA-3973 + GCCUGGAGACCAGUAUCGGCU 21 7822

SCNNlA-3974 + GGCCUGGAGACCAGUAUCGGCU 22 7823

SCNNlA-3975 + CGGCCUGGAGACCAGUAUCGGCU 23 7824

SCNNlA-3976 + UCGGCCUGGAGACCAGUAUCGGCU 24 7825

SCNNlA-3977 + ACAGGAGGGUGACCAUCU 18 7826

SCNNlA-3978 + GACAGGAGGGUGACCAUCU 19 7827

SCNNlA-3979 + GGACAGGAGGGUGACCAUCU 20 7828

SCNNlA-3980 + UGGACAGGAGGGUGACCAUCU 21 7829

SCNNlA-3981 + UUGGACAGGAGGGUGACCAUCU 22 7830

SCNNlA-3982 + GUUGGACAGGAGGGUGACCAUCU 23 7831

SCNNlA-3983 + GGUUGGACAGGAGGGUGACCAUCU 24 7832

SCNNlA-3984 + AAACCUCUCCUUCCCUCU 18 7833

SCNNlA-3985 + GAAACCUCUCCUUCCCUCU 19 7834

SCNNlA-3986 + AGAAACCUCUCCUUCCCUCU 20 7835

SCNNlA-3987 + GAGAAACCUCUCCUUCCCUCU 21 7836

SCNNlA-3988 + UGAGAAACCUCUCCUUCCCUCU 22 7837

SCNNlA-3989 + GUGAGAAACCUCUCCUUCCCUCU 23 7838

SCNNlA-3990 + UGUGAGAAACCUCUCCUUCCCUCU 24 7839

SCNNlA-3991 + AAACAGCCCAGGUGGUCU 18 7840

SCNNlA-3992 + GAAACAGCCCAGGUGGUCU 19 7841

SCNNlA-3993 + UGAAACAGCCCAGGUGGUCU 20 7842

SCNNlA-3994 + GUGAAACAGCCCAGGUGGUCU 21 7843

SCNNlA-3995 + GGUGAAACAGCCCAGGUGGUCU 22 7844

SCNNlA-3996 + UGGUGAAACAGCCCAGGUGGUCU 23 7845

SCNNlA-3997 + UUGGUGAAACAGCCCAGGUGGUCU 24 7846

SCNNlA-3998 + UGGGGUGGGGGCAGAAGU 18 7847

SCNNlA-3999 + AUGGGGUGGGGGCAGAAGU 19 7848

SCNNlA-1279 + CAUGGGGUGGGGGCAGAAGU 20 5128

SCNNlA-4000 + ACAUGGGGUGGGGGCAGAAGU 21 7849

SCNNlA-4001 + GACAUGGGGUGGGGGCAGAAGU 22 7850

1289

5535.1 SCNNlA-4002 + AGACAUGGGGUGGGGGCAGAAGU 23 7851

SCNNlA-4003 + GAGACAUGGGGUGGGGGCAGAAGU 24

7852

SCNNlA-4004 + GGACACAGAGACUAGAGU 18 7853

SCNNlA-4005 + UGGACACAGAGACUAGAGU 19 7854

SCNNlA-4006 + CUGGACACAGAGACUAGAGU 20 7855

SCNNlA-4007 + ACUGGACACAGAGACUAGAGU 21 7856

SCNNlA-4008 + CACUGGACACAGAGACUAGAGU 22 7857

SCNNlA-4009 + GCACUGGACACAGAGACUAGAGU 23 7858

SCNNlA-4010 + UGCACUGGACACAGAGACUAGAGU 24 7859

SCNNlA-4011 + CCACUCCAUUUCUUAGGU 18 7860

SCNNlA-4012 + GCCACUCCAUUUCUUAGGU 19 7861

SCNNlA-4013 + GGCCACUCCAUUUCUUAGGU 20 7862

SCNNlA-4014 + UGGCCACUCCAUUUCUUAGGU 21 7863

SCNNlA-4015 + UUGGCCACUCCAUUUCUUAGGU 22 7864

SCNNlA-4016 + UUUGGCCACUCCAUUUCUUAGGU 23 7865

SCNNlA-4017 + CUUUGGCCACUCCAUUUCUUAGGU 24 7866

SCNNlA-4018 + AGGUGUGGGGCAGAGGGU 18 7867

SCNNlA-4019 + UAGGUGUGGGGCAGAGGGU 19 7868

SCNNlA-1286 + UUAGGUGUGGGGCAGAGGGU 20 5135

SCNNlA-4020 + CUUAGGUGUGGGGCAGAGGGU 21 7869

SCNNlA-4021 + UCUUAGGUGUGGGGCAGAGGGU 22 7870

SCNNlA-4022 + UUCUUAGGUGUGGGGCAGAGGGU 23 7871

SCNNlA-4023 + UUUCUUAGGUGUGGGGCAGAGGGU 24

7872

SCNNlA-4024 + GGAAAGAGAGAGUAGGGU 18 7873

SCNNlA-4025 + AGGAAAGAGAGAGUAGGGU 19 7874

SCNNlA-4026 + CAGGAAAGAGAGAGUAGGGU 20 7875

SCNNlA-4027 + UCAGGAAAGAGAGAGUAGGGU 21 7876

SCNNlA-4028 + AUCAGGAAAGAGAGAGUAGGGU 22 7877

SCNNlA-4029 + UAUCAGGAAAGAGAGAGUAGGGU 23 7878

SCNNlA-4030 + UUAUCAGGAAAGAGAGAGUAGGGU 24

7879

SCNNlA-4031 + AGGACAGAGACAUGGGGU 18 7880

SCNNlA-4032 + AAGGACAGAGACAUGGGGU 19 7881

SCNNlA-1287 + CAAGGACAGAGACAUGGGGU 20 5136

SCNNlA-4033 + ACAAGGACAGAGACAUGGGGU 21 7882

SCNNlA-4034 + GACAAGGACAGAGACAUGGGGU 22 7883

SCNNlA-4035 + GGACAAGGACAGAGACAUGGGGU 23 7884

SCNNlA-4036 + GGGACAAGGACAGAGACAUGGGGU 24 7885

SCNNlA-4037 + UGAAACAGCCCAGGUGGU 18 7886

SCNNlA-4038 + GUGAAACAGCCCAGGUGGU 19 7887

1290

5535.1 SCNNlA-4039 + GGUGAAACAGCCCAGGUGGU 20 7888

SCNNlA-4040 + UGGUGAAACAGCCCAGGUGGU 21 7889

SCNNlA-4041 + UUGGUGAAACAGCCCAGGUGGU 22 7890

SCNNlA-4042 + CUUGGUGAAACAGCCCAGGUGGU 23 7891

SCNNlA-4043 + ACUUGGUGAAACAGCCCAGGUGGU 24 7892

SCNNlA-4044 + AGGAGGGUGACCAUCUGU 18 7893

SCNNlA-4045 + CAGGAGGGUGACCAUCUGU 19 7894

SCNNlA-4046 + ACAGGAGGGUGACCAUCUGU 20 7895

SCNNlA-4047 + GACAGGAGGGUGACCAUCUGU 21 7896

SCNNlA-4048 + GGACAGGAGGGUGACCAUCUGU 22 7897

SCNNlA-4049 + UGGACAGGAGGGUGACCAUCUGU 23 7898

SCNNlA-4050 + UUGGACAGGAGGGUGACCAUCUGU 24 7899

SCNNlA-4051 + UAUCGGCUUCGGAACCUU 18 7900

SCNNlA-4052 + GUAUCGGCUUCGGAACCUU 19 7901

SCNNlA-1297 + AGUAUCGGCUUCGGAACCUU 20 5146

SCNNlA-4053 + CAGUAUCGGCUUCGGAACCUU 21 7902

SCNNlA-4054 + CCAGUAUCGGCUUCGGAACCUU 22 7903

SCNNlA-4055 + ACCAGUAUCGGCUUCGGAACCUU 23 7904

SCNNlA-4056 + GACCAGUAUCGGCUUCGGAACCUU 24 7905

SCNNlA-4057 + GGAGACCAGUAUCGGCUU 18 7906

SCNNlA-4058 + UGGAGACCAGUAUCGGCUU 19 7907

SCNNlA-1298 + CUGGAGACCAGUAUCGGCUU 20 5147

SCNNlA-4059 + CCUGGAGACCAGUAUCGGCUU 21 7908

SCNNlA-4060 + GCCUGGAGACCAGUAUCGGCUU 22 7909

SCNNlA-4061 + GGCCUGGAGACCAGUAUCGGCUU 23 7910

SCNNlA-4062 + CGGCCUGGAGACCAGUAUCGGCUU 24 7911

SCNNlA-4063 + GUCACAGUACUCCACGUU 18 7912

SCNNlA-4064 + AGUCACAGUACUCCACGUU 19 7913

SCNNlA-4065 + UAGUCACAGUACUCCACGUU 20 7914

SCNNlA-4066 + GUAGUCACAGUACUCCACGUU 21 7915

SCNNlA-4067 + UGUAGUCACAGUACUCCACGUU 22 7916

SCNNlA-4068 + CUGUAGUCACAGUACUCCACGUU 23 7917

SCNNlA-4069 + UCUGUAGUCACAGUACUCCACGUU 24 7918

SCNNlA-4070 - CAG UG CAACCAG AACAAA 18 7919

SCNNlA-4071 - CCAGUG CAACCAG AACAAA 19 7920

SCNNlA-4072 - U CC AG U G CAACCAG AACAAA 20 7921

SCNNlA-4073 - GUCCAGUGCAACCAGAACAAA 21 7922

SCNNlA-4074 - UGUCCAGUGCAACCAGAACAAA 22 7923

SCNNlA-4075 - GUGUCCAGUG C A AC CAG AACAAA 23 7924

SCNNlA-4076 - UGUGUCCAGUG CAACCAG AACAAA 24 7925

SCNNlA-4077 - AGGUACCCGGAAAUUAAA 18 7926

SCNNlA-4078 - CAGG U ACCCGG AAAU U AAA 19 7927

1291

5535.1 SCNNlA-4079 - UCAGGUACCCGGAAAUUAAA 20 7928

SCNNlA-4080 - UUCAGGUACCCGGAAAUUAAA 21 7929

SCNNlA-4081 - CU U CAGG U ACCCGG AAAU U AAA 22 7930

SCNNlA-4082 - CCU U CAGG U ACCCGG AAAU U AAA 23 7931

SCNNlA-4083 - CCCUUCAGGUACCCGGAAAUUAAA 24 7932

SCNNlA-4084 - CUGCCCCACACCUAAGAA 18 7933

SCNNlA-4085 - UCUGCCCCACACCUAAGAA 19 7934

SCNNlA-4086 - CUCUGCCCCACACCUAAGAA 20 7935

SCNNlA-4087 - CCUCUGCCCCACACCUAAGAA 21 7936

SCNNlA-4088 - CCCUCUGCCCCACACCUAAGAA 22 7937

SCNNlA-4089 - ACCCUCUGCCCCACACCUAAGAA 23 7938

SCNNlA-4090 - CACCCUCUGCCCCACACCUAAGAA 24 7939

SCNNlA-4091 - GUCCAACCUGGGCAGCCA 18 7940

SCNNlA-4092 - UGUCCAACCUGGGCAGCCA 19 7941

SCNNlA-4093 - CUGUCCAACCUGGGCAGCCA 20 7942

SCNNlA-4094 - CCUGUCCAACCUGGGCAGCCA 21 7943

SCNNlA-4095 - UCCUGUCCAACCUGGGCAGCCA 22 7944

SCNNlA-4096 - CUCCUGUCCAACCUGGGCAGCCA 23 7945

SCNNlA-4097 - CCUCCUGUCCAACCUGGGCAGCCA 24 7946

SCNNlA-4098 - UCCUGGGGUGAGACUCCA 18 7947

SCNNlA-4099 - UUCCUGGGGUGAGACUCCA 19 7948

SCNNlA-904 - GUUCCUGGGGUGAGACUCCA 20 4753

SCNNlA-4100 - AGUUCCUGGGGUGAGACUCCA 21 7949

SCNNlA-4101 - CAGUUCCUGGGGUGAGACUCCA 22 7950

SCNNlA-4102 - ACAGUUCCUGGGGUGAGACUCCA 23 7951

SCNNlA-4103 - CACAGUUCCUGGGGUGAGACUCCA 24 7952

SCNNlA-4104 - GGCCCCCGCCCAUCUCCA 18 7953

SCNNlA-4105 - GGGCCCCCGCCCAUCUCCA 19 7954

SCNNlA-907 - UGGGCCCCCGCCCAUCUCCA 20 4756

SCNNlA-4106 - CUGGGCCCCCGCCCAUCUCCA 21 7955

SCNNlA-4107 - CCUGGGCCCCCGCCCAUCUCCA 22 7956

SCNNlA-4108 - CCCUGGGCCCCCGCCCAUCUCCA 23 7957

SCNNlA-4109 - ACCCUGGGCCCCCGCCCAUCUCCA 24 7958

SCNNlA-4110 - AGGAGCUGGACCGCAUCA 18 7959

SCNNlA-4111 - GAGGAGCUGGACCGCAUCA 19 7960

SCNNlA-4112 - GGAGGAGCUGGACCGCAUCA 20 7961

SCNNlA-4113 - UGGAGGAGCUGGACCGCAUCA 21 7962

SCNNlA-4114 - CUGGAGGAGCUGGACCGCAUCA 22 7963

SCNNlA-4115 - GCUGGAGGAGCUGGACCGCAUCA 23 7964

SCNNlA-4116 - AGCUGGAGGAGCUGGACCGCAUCA 24 7965

SCNNlA-4117 - GGUCCCGCCCCCGCCUCA 18 7966

SCNNlA-4118 - GGGUCCCGCCCCCGCCUCA 19 7967

1292

5535.1 SCNNlA-924 - AGGGUCCCGCCCCCGCCUCA 20 4773

SCNNlA-4119 - GAGGGUCCCGCCCCCGCCUCA 21 7968

SCNNlA-4120 - UGAGGGUCCCGCCCCCGCCUCA 22 7969

SCNNlA-4121 - CUGAGGGUCCCGCCCCCGCCUCA 23 7970

SCNNlA-4122 - CCUGAGGGUCCCGCCCCCGCCUCA 24 7971

SCNNlA-4123 - AAGUCAACAUCUUCUUCA 18 7972

SCNNlA-4124 - AAAGUCAACAUCUUCUUCA 19 7973

SCNNlA-928 - C A A AG UCAACAUCUUCUUCA 20 4777

SCNNlA-4125 - CCA AAG U C AACAU C U U C U U C A 21 7974

SCNNlA-4126 - GCCAAAGUCAACAUCUUCUUCA 22 7975

SCNNlA-4127 - GGCCAAAGUCAACAUCUUCUUCA 23 7976

SCNNlA-4128 - UGGCCAAAGUCAACAUCUUCUUCA 24 7977

SCNNlA-4129 - UUGGUGUAUGUGGGUUCA 18 7978

SCNNlA-4130 - CUUGGUGUAUGUGGGUUCA 19 7979

SCNNlA-4131 - UCUUGGUGUAUGUGGGUUCA 20 7980

SCNNlA-4132 - CUCUUGGUGUAUGUGGGUUCA 21 7981

SCNNlA-4133 - UCUCUUGGUGUAUGUGGGUUCA 22 7982

SCNNlA-4134 - AUCUCUUGGUGUAUGUGGGUUCA 23 7983

SCNNlA-4135 - GAUCUCUUGGUGUAUGUGGGUUCA 24

7984

SCNNlA-4136 - UCUGGGGGGGCCCUGAGA 18 7985

SCNNlA-4137 - CUCUGGGGGGGCCCUGAGA 19 7986

SCNNlA-938 - CCUCUGGGGGGGCCCUGAGA 20 4787

SCNNlA-4138 - UCCUCUGGGGGGGCCCUGAGA 21 7987

SCNNlA-4139 - GUCCUCUGGGGGGGCCCUGAGA 22 7988

SCNNlA-4140 - UGUCCUCUGGGGGGGCCCUGAGA 23 7989

SCNNlA-4141 - CUGUCCUCUGGGGGGGCCCUGAGA 24 7990

SCNNlA-4142 - UACUGGUCUCCAGGCCGA 18 7991

SCNNlA-4143 - AUACUGGUCUCCAGGCCGA 19 7992

SCNNlA-943 - GAUACUGGUCUCCAGGCCGA 20 4792

SCNNlA-4144 - CGAUACUGGUCUCCAGGCCGA 21 7993

SCNNlA-4145 - CCGAUACUGGUCUCCAGGCCGA 22 7994

SCNNlA-4146 - GCCGAUACUGGUCUCCAGGCCGA 23 7995

SCNNlA-4147 - AGCCGAUACUGGUCUCCAGGCCGA 24 7996

SCNNlA-4148 - UUCCAGAUGCUAUCGCGA 18 7997

SCNNlA-4149 - CUUCCAGAUGCUAUCGCGA 19 7998

SCNNlA-4150 - UCUUCCAGAUGCUAUCGCGA 20 7999

SCNNlA-4151 - GUCUUCCAGAUGCUAUCGCGA 21 8000

SCNNlA-4152 - GGUCUUCCAGAUGCUAUCGCGA 22 8001

SCNNlA-4153 - GGGUCUUCCAGAUGCUAUCGCGA 23 8002

SCNNlA-4154 - UGGGUCUUCCAGAUGCUAUCGCGA 24 8003

SCNNlA-4155 - CCAGGUGGACUGGAAGGA 18 8004

1293

5535.1 SCNNlA-4156 - CCCAGGUGGACUGGAAGGA 19 8005

SCNNlA-4157 - CCCCAGGUGGACUGGAAGGA 20 8006

SCNNlA-4158 - CCCCCAGGUGGACUGGAAGGA 21 8007

SCNNlA-4159 - ACCCCCAGGUGGACUGGAAGGA 22 8008

SCNNlA-4160 - AACCCCCAGGUGGACUGGAAGGA 23 8009

SCNNlA-4161 - CAACCCCCAGGUGGACUGGAAGGA 24 8010

SCNNlA-4162 - GGGGGGCCCUGAGAGGGA 18 8011

SCNNlA-4163 - GGGGGGGCCCUGAGAGGGA 19 8012

SCNNlA-954 - UGGGGGGGCCCUGAGAGGGA 20 4803

SCNNlA-4164 - CUGGGGGGGCCCUGAGAGGGA 21 8013

SCNNlA-4165 - UCUGGGGGGGCCCUGAGAGGGA 22 8014

SCNNlA-4166 - CUCUGGGGGGGCCCUGAGAGGGA 23 8015

SCNNlA-4167 - CCUCUGGGGGGGCCCUGAGAGGGA 24 8016

SCNNlA-4168 - CGGUAGGUCGUGCCUGGA 18 8017

SCNNlA-4169 - ACGGUAGGUCGUGCCUGGA 19 8018

SCNNlA-962 - CACGGUAGGUCGUGCCUGGA 20 4811

SCNNlA-4170 - UCACGGUAGGUCGUGCCUGGA 21 8019

SCNNlA-4171 - GUCACGGUAGGUCGUGCCUGGA 22 8020

SCNNlA-4172 - UGUCACGGUAGGUCGUGCCUGGA 23 8021

SCNNlA-4173 - CUGUCACGGUAGGUCGUGCCUGGA 24 8022

SCNNlA-4174 - CAACAACCCCCAGGUGGA 18 8023

SCNNlA-4175 - ACAACAACCCCCAGGUGGA 19 8024

SCNNlA-4176 - GACAACAACCCCCAGGUGGA 20 8025

SCNNlA-4177 - GGACAACAACCCCCAGGUGGA 21 8026

SCNNlA-4178 - GGGACAACAACCCCCAGGUGGA 22 8027

SCNNlA-4179 - CGGGACAACAACCCCCAGGUGGA 23 8028

SCNNlA-4180 - GCGGGACAACAACCCCCAGGUGGA 24 8029

SCNNlA-4181 - CCUCUGGGGGGGCCCUGA 18 8030

SCNNlA-4182 - UCCUCUGGGGGGGCCCUGA 19 8031

SCNNlA-4183 - GUCCUCUGGGGGGGCCCUGA 20 8032

SCNNlA-4184 - UGUCCUCUGGGGGGGCCCUGA 21 8033

SCNNlA-4185 - CUGUCCUCUGGGGGGGCCCUGA 22 8034

SCNNlA-4186 - CCUGUCCUCUGGGGGGGCCCUGA 23 8035

SCNNlA-4187 - ACCUGUCCUCUGGGGGGGCCCUGA 24 8036

SCNNlA-4188 - GGAAGGCAAGGAUGCUGA 18 8037

SCNNlA-4189 - AGGAAGGCAAGGAUGCUGA 19 8038

SCNNlA-4190 - GAGGAAGGCAAGGAUGCUGA 20 8039

SCNNlA-4191 - UGAGGAAGGCAAGGAUGCUGA 21 8040

SCNNlA-4192 - AUGAGGAAGGCAAGGAUGCUGA 22 8041

SCNNlA-4193 - CAUGAGGAAGGCAAGGAUGCUGA 23 8042

SCNNlA-4194 - GCAUGAGGAAGGCAAGGAUGCUGA 24 8043

SCNNlA-4195 - CCCUGCUGUCCACAGUGA 18 8044

1294

5535.1 SCNNlA-4196 - CCCCUGCUGUCCACAGUGA 19 8045

SCNNlA-4197 - UCCCCUGCUGUCCACAGUGA 20 8046

SCNNlA-4198 - UUCCCCUGCUGUCCACAGUGA 21 8047

SCNNlA-4199 - AUUCCCCUGCUGUCCACAGUGA 22 8048

SCNNlA-4200 - CAUUCCCCUGCUGUCCACAGUGA 23 8049

SCNNlA-4201 - UCAUUCCCCUGCUGUCCACAGUGA 24 8050

SCNNlA-4202 - CGUGGAGUACUGUGACUA 18 8051

SCNNlA-4203 - ACGUGGAGUACUGUGACUA 19 8052

SCNNlA-4204 - AACGUGGAGUACUGUGACUA 20 8053

SCNNlA-4205 - GAACGUGGAGUACUGUGACUA 21 8054

SCNNlA-4206 - AGAACGUGGAGUACUGUGACUA 22 8055

SCNNlA-4207 - CAGAACGUGGAGUACUGUGACUA 23 8056

SCNNlA-4208 - CCAGAACGUGGAGUACUGUGACUA 24 8057

SCNNlA-4209 - CUUCCACCACCCGAUGUA 18 8058

SCNNlA-4210 - ACUUCCACCACCCGAUGUA 19 8059

SCNNlA-975 - CACUUCCACCACCCGAUGUA 20 4824

SCNNlA-4211 - UCACUUCCACCACCCGAUGUA 21 8060

SCNNlA-4212 - CUCACUUCCACCACCCGAUGUA 22 8061

SCNNlA-4213 - UCUCACUUCCACCACCCGAUGUA 23 8062

SCNNlA-4214 - CUCUCACUUCCACCACCCGAUGUA 24 8063

SCNNlA-4215 - UCAGGUACCCGGAAAUUA 18 8064

SCNNlA-4216 - UUCAGGUACCCGGAAAUUA 19 8065

SCNNlA-4217 - CUUCAGGUACCCGGAAAUUA 20 8066

SCNNlA-4218 - CCUUCAGGUACCCGGAAAUUA 21 8067

SCNNlA-4219 - CCCUUCAGGUACCCGGAAAUUA 22 8068

SCNNlA-4220 - CCCCUUCAGGUACCCGGAAAUUA 23 8069

SCNNlA-4221 - GCCCCUUCAGGUACCCGGAAAUUA 24 8070

SCNNlA-4222 - AAU U ACACCG U CAACAAC 18 8071

SCNNlA-4223 - CAAU U ACACCG U CAACAAC 19 8072

SCNNlA-4224 - ACAAU U ACACCG U CAACAAC 20 8073

SCNNlA-4225 - AACAAU U ACACCG U CAACAAC 21 8074

SCNNlA-4226 - GAACAAU U ACACCG U CAACAAC 22 8075

SCNNlA-4227 - AG AACAAU U ACACCG U CAACAAC 23 8076

SCNNlA-4228 - CAG AACAAU U ACACCG U CAACAAC 24 8077

SCNNlA-4229 - GUCACCCUCCUGUCCAAC 18 8078

SCNNlA-4230 - GGUCACCCUCCUGUCCAAC 19 8079

SCNNlA-4231 - UGGUCACCCUCCUGUCCAAC 20 8080

SCNNlA-4232 - AUGGUCACCCUCCUGUCCAAC 21 8081

SCNNlA-4233 - GAUGGUCACCCUCCUGUCCAAC 22 8082

SCNNlA-4234 - AGAUGGUCACCCUCCUGUCCAAC 23 8083

SCNNlA-4235 - CAGAUGGUCACCCUCCUGUCCAAC 24 8084

SCNNlA-4236 - CUCUGUGUCCAGUGCAAC 18 8085

1295

5535.1 SCNNlA-4237 - UCUCUGUGUCCAGUGCAAC 19 8086

SCNNlA-4238 - GUCUCUGUGUCCAGUGCAAC 20 8087

SCNNlA-4239 - AGUCUCUGUGUCCAGUGCAAC 21 8088

SCNNlA-4240 - UAGUCUCUGUGUCCAGUGCAAC 22 8089

SCNNlA-4241 - CUAGUCUCUGUGUCCAGUGCAAC 23 8090

SCNNlA-4242 - UCUAGUCUCUGUGUCCAGUGCAAC 24 8091

SCNNlA-4243 - UAUCCGCGGCCCCAGAAC 18 8092

SCNNlA-4244 - CUAUCCGCGGCCCCAGAAC 19 8093

SCNNlA-4245 - UCUAUCCGCGGCCCCAGAAC 20 8094

SCNNlA-4246 - UUCUAUCCGCGGCCCCAGAAC 21 8095

SCNNlA-4247 - CUUCUAUCCGCGGCCCCAGAAC 22 8096

SCNNlA-4248 - UCUUCUAUCCGCGGCCCCAGAAC 23 8097

SCNNlA-4249 - AUCUUCUAUCCGCGGCCCCAGAAC 24 8098

SCNNlA-4250 - GACUUCUCCUCAGACCAC 18 8099

SCNNlA-4251 - UGACUUCUCCUCAGACCAC 19 8100

SCNNlA-4252 - UUGACUUCUCCUCAGACCAC 20 8101

SCNNlA-4253 - GUUGACUUCUCCUCAGACCAC 21 8102

SCNNlA-4254 - GGUUGACUUCUCCUCAGACCAC 22 8103

SCNNlA-4255 - AGGUUGACUUCUCCUCAGACCAC 23 8104

SCNNlA-4256 - CAGGUUGACUUCUCCUCAGACCAC 24 8105

SCNNlA-4257 - AGGAAACCCUGGACAGAC 18 8106

SCNNlA-4258 - UAGGAAACCCUGGACAGAC 19 8107

SCNNlA-4259 - AUAGGAAACCCUGGACAGAC 20 8108

SCNNlA-4260 - CAUAGGAAACCCUGGACAGAC 21 8109

SCNNlA-4261 - UCAUAGGAAACCCUGGACAGAC 22 8110

SCNNlA-4262 - UUCAUAGGAAACCCUGGACAGAC 23 8111

SCNNlA-4263 - GUUCAUAGGAAACCCUGGACAGAC 24 8112

SCNNlA-4264 - CAGGUGGACUGGAAGGAC 18 8113

SCNNlA-4265 - CCAGGUGGACUGGAAGGAC 19 8114

SCNNlA-988 - CCCAGGUGGACUGGAAGGAC 20 4837

SCNNlA-4266 - CCCCAGGUGGACUGGAAGGAC 21 8115

SCNNlA-4267 - CCCCCAGGUGGACUGGAAGGAC 22 8116

SCNNlA-4268 - ACCCCCAGGUGGACUGGAAGGAC 23 8117

SCNNlA-4269 - AACCCCCAGGUGGACUGGAAGGAC 24 8118

SCNNlA-4270 - AACAACCCCCAGGUGGAC 18 8119

SCNNlA-4271 - CAACAACCCCCAGGUGGAC 19 8120

SCNNlA-990 - ACAACAACCCCCAGGUGGAC 20 4839

SCNNlA-4272 - GACAACAACCCCCAGGUGGAC 21 8121

SCNNlA-4273 - GG ACAACAACCCCCAGGUGGAC 22 8122

SCNNlA-4274 - GGGACAACAACCCCCAGGUGGAC 23 8123

SCNNlA-4275 - CGGGACAACAACCCCCAGGUGGAC 24 8124

SCNNlA-4276 - UGCUAUACUUUCAAUGAC 18 8125

1296

5535.1 SCNNlA-4277 - CUGCUAUACUUUCAAUGAC 19 8126

SCNNlA-4278 - ACUGCUAUACUUUCAAUGAC 20 8127

SCNNlA-4279 - AACUGCUAUACUUUCAAUGAC 21 8128

SCNNlA-4280 - AAACUGCUAUACUUUCAAUGAC 22 8129

SCNNlA-4281 - GAAACUGCUAUACUUUCAAUGAC 23 8130

SCNNlA-4282 - GGAAACUGCUAUACUUUCAAUGAC 24 8131

SCNNlA-4283 - GAAGGCAAGGAUGCUGAC 18 8132

SCNNlA-4284 - GGAAGGCAAGGAUGCUGAC 19 8133

SCNNlA-992 - AGGAAGGCAAGGAUGCUGAC 20 4841

SCNNlA-4285 - GAGGAAGGCAAGGAUGCUGAC 21 8134

SCNNlA-4286 - UGAGGAAGGCAAGGAUGCUGAC 22 8135

SCNNlA-4287 - AUGAGGAAGGCAAGGAUGCUGAC 23 8136

SCNNlA-4288 - CAUGAGGAAGGCAAGGAUGCUGAC 24 8137

SCNNlA-4289 - CCUGCUGUCCACAGUGAC 18 8138

SCNNlA-4290 - CCCUGCUGUCCACAGUGAC 19 8139

SCNNlA-993 - CCCCUGCUGUCCACAGUGAC 20 4842

SCNNlA-4291 - UCCCCUGCUGUCCACAGUGAC 21 8140

SCNNlA-4292 - UUCCCCUGCUGUCCACAGUGAC 22 8141

SCNNlA-4293 - AUUCCCCUGCUGUCCACAGUGAC 23 8142

SCNNlA-4294 - CAUUCCCCUGCUGUCCACAGUGAC 24 8143

SCNNlA-4295 - CCUCGCCCCUUCAGGUAC 18 8144

SCNNlA-4296 - CCCUCGCCCCUUCAGGUAC 19 8145

SCNNlA-4297 - CCCCUCGCCCCUUCAGGUAC 20 8146

SCNNlA-4298 - UCCCCUCGCCCCUUCAGGUAC 21 8147

SCNNlA-4299 - UUCCCCUCGCCCCUUCAGGUAC 22 8148

SCNNlA-4300 - CUUCCCCUCGCCCCUUCAGGUAC 23 8149

SCNNlA-4301 - UCUUCCCCUCGCCCCUUCAGGUAC 24 8150

SCNNlA-4302 - GUGGGUUCAUAGGAAACC 18 8151

SCNNlA-4303 - UGUGGGUUCAUAGGAAACC 19 8152

SCNNlA-4304 - AUGUGGGUUCAUAGGAAACC 20 8153

SCNNlA-4305 - UAUGUGGGUUCAUAGGAAACC 21 8154

SCNNlA-4306 - GUAUGUGGGUUCAUAGGAAACC 22 8155

SCNNlA-4307 - UGUAUGUGGGUUCAUAGGAAACC 23 8156

SCNNlA-4308 - GUGUAUGUGGGUUCAUAGGAAACC 24 8157

SCNNlA-4309 - CCCCCUGCCUAUGCCACC 18 8158

SCNNlA-4310 - UCCCCCUGCCUAUGCCACC 19 8159

SCNNlA-4311 - CUCCCCCUGCCUAUGCCACC 20 8160

SCNNlA-4312 - CCUCCCCCUGCCUAUGCCACC 21 8161

SCNNlA-4313 - CCCUCCCCCUGCCUAUGCCACC 22 8162

SCNNlA-4314 - CCCCUCCCCCUGCCUAUGCCACC 23 8163

SCNNlA-4315 - GCCCCUCCCCCUGCCUAUGCCACC 24 8164

SCNNlA-4316 - CUCGCCCCUUCAGGUACC 18 8165

1297

5535.1 SCNNlA-4317 - CCUCGCCCCUUCAGGUACC 19 8166

SCNNlA-1007 - CCCUCGCCCCUUCAGGUACC 20 4856

SCNNlA-4318 - CCCCUCGCCCCUUCAGGUACC 21 8167

SCNNlA-4319 - UCCCCUCGCCCCUUCAGGUACC 22 8168

SCNNlA-4320 - UUCCCCUCGCCCCUUCAGGUACC 23 8169

SCNNlA-4321 - CUUCCCCUCGCCCCUUCAGGUACC 24 8170

SCNNlA-4322 - AUCUUCUAUCCGCGGCCC 18 8171

SCNNlA-4323 - CAUCUUCUAUCCGCGGCCC 19 8172

SCNNlA-4324 - ACAUCUUCUAUCCGCGGCCC 20 8173

SCNNlA-4325 - UACAUCUUCUAUCCGCGGCCC 21 8174

SCNNlA-4326 - CUACAUCUUCUAUCCGCGGCCC 22 8175

SCNNlA-4327 - CCUACAUCUUCUAUCCGCGGCCC 23 8176

SCNNlA-4328 - GCCUACAUCUUCUAUCCGCGGCCC 24 8177

SCNNlA-4329 - CAGAGACUCUGCCAUCCC 18 8178

SCNNlA-4330 - CCAGAGACUCUGCCAUCCC 19 8179

SCNNlA-1023 - GCCAGAGACUCUGCCAUCCC 20 4872

SCNNlA-4331 - UGCCAGAGACUCUGCCAUCCC 21 8180

SCNNlA-4332 - CUGCCAGAGACUCUGCCAUCCC 22 8181

SCNNlA-4333 - GCUGCCAGAGACUCUGCCAUCCC 23 8182

SCNNlA-4334 - GGCUGCCAGAGACUCUGCCAUCCC 24 8183

SCNNlA-4335 - GGUGAGGCCCGCAGCGCC 18 8184

SCNNlA-4336 - UGGUGAGGCCCGCAGCGCC 19 8185

SCNNlA-4337 - CUGGUGAGGCCCGCAGCGCC 20 8186

SCNNlA-4338 - GCUGGUGAGGCCCGCAGCGCC 21 8187

SCNNlA-4339 - AGCUGGUGAGGCCCGCAGCGCC 22 8188

SCNNlA-4340 - CAGCUGGUGAGGCCCGCAGCGCC 23 8189

SCNNlA-4341 - CCAGCUGGUGAGGCCCGCAGCGCC 24 8190

SCNNlA-4342 - GAUACUGGUCUCCAGGCC 18 8191

SCNNlA-4343 - CGAUACUGGUCUCCAGGCC 19 8192

SCNNlA-4344 - CCGAUACUGGUCUCCAGGCC 20 8193

SCNNlA-4345 - GCCGAUACUGGUCUCCAGGCC 21 8194

SCNNlA-4346 - AGCCGAUACUGGUCUCCAGGCC 22 8195

SCNNlA-4347 - AAGCCGAUACUGGUCUCCAGGCC 23 8196

SCNNlA-4348 - GAAGCCGAUACUGGUCUCCAGGCC 24 8197

SCNNlA-4349 - GAUGCUGACUGGGAGGCC 18 8198

SCNNlA-4350 - GGAUGCUGACUGGGAGGCC 19 8199

SCNNlA-1028 - AGGAUGCUGACUGGGAGGCC 20 4877

SCNNlA-4351 - AAGGAUGCUGACUGGGAGGCC 21 8200

SCNNlA-4352 - CAAGGAUGCUGACUGGGAGGCC 22 8201

SCNNlA-4353 - GCAAGGAUGCUGACUGGGAGGCC 23 8202

SCNNlA-4354 - GGCAAGGAUGCUGACUGGGAGGCC 24 8203

SCNNlA-4355 - CUGUCCUCUGGGGGGGCC 18 8204

1298

5535.1 SCNNlA-4356 - CCUGUCCUCUGGGGGGGCC 19 8205

SCNNlA-4357 - ACCUGUCCUCUGGGGGGGCC 20 8206

SCNNlA-4358 - CACCUGUCCUCUGGGGGGGCC 21 8207

SCNNlA-4359 - CCACCUGUCCUCUGGGGGGGCC 22 8208

SCNNlA-4360 - UCCACCUGUCCUCUGGGGGGGCC 23 8209

SCNNlA-4361 - CUCCACCUGUCCUCUGGGGGGGCC 24 8210

SCNNlA-4362 - CCAGAGACUCUGCCAUCC 18 8211

SCNNlA-4363 - GCCAGAGACUCUGCCAUCC 19 8212

SCNNlA-4364 - UGCCAGAGACUCUGCCAUCC 20 8213

SCNNlA-4365 - CUGCCAGAGACUCUGCCAUCC 21 8214

SCNNlA-4366 - GCUGCCAGAGACUCUGCCAUCC 22 8215

SCNNlA-4367 - GGCUGCCAGAGACUCUGCCAUCC 23 8216

SCNNlA-4368 - AGGCUGCCAGAGACUCUGCCAUCC 24 8217

SCNNlA-4369 - UUCCUGGGGUGAGACUCC 18 8218

SCNNlA-4370 - GUUCCUGGGGUGAGACUCC 19 8219

SCNNlA-1037 - AGUUCCUGGGGUGAGACUCC 20 4886

SCNNlA-4371 - CAGUUCCUGGGGUGAGACUCC 21 8220

SCNNlA-4372 - ACAGUUCCUGGGGUGAGACUCC 22 8221

SCNNlA-4373 - CACAGUUCCUGGGGUGAGACUCC 23 8222

SCNNlA-4374 - GCACAGUUCCUGGGGUGAGACUCC 24 8223

SCNNlA-4375 - GGGCCCCCGCCCAUCUCC 18 8224

SCNNlA-4376 - UGGGCCCCCGCCCAUCUCC 19 8225

SCNNlA-1040 - CUGGGCCCCCGCCCAUCUCC 20 4889

SCNNlA-4377 - CCUGGGCCCCCGCCCAUCUCC 21 8226

SCNNlA-4378 - CCCUGGGCCCCCGCCCAUCUCC 22 8227

SCNNlA-4379 - ACCCUGGGCCCCCGCCCAUCUCC 23 8228

SCNNlA-4380 - CACCCUGGGCCCCCGCCCAUCUCC 24 8229

SCNNlA-4381 - GUAUUCACUCCUGCUUCC 18 8230

SCNNlA-4382 - UGUAUUCACUCCUGCUUCC 19 8231

SCNNlA-1046 - GUGUAUUCACUCCUGCUUCC 20 4895

SCNNlA-4383 - UGUGUAUUCACUCCUGCUUCC 21 8232

SCNNlA-4384 - GUGUGUAUUCACUCCUGCUUCC 22 8233

SCNNlA-4385 - GGUGUGUAUUCACUCCUGCUUCC 23 8234

SCNNlA-4386 - AGGUGUGUAUUCACUCCUGCUUCC 24 8235

SCNNlA-4387 - GACACCCCCAUUCUUUCC 18 8236

SCNNlA-4388 - UGACACCCCCAUUCUUUCC 19 8237

SCNNlA-4389 - AUGACACCCCCAUUCUUUCC 20 8238

SCNNlA-4390 - GAUGACACCCCCAUUCUUUCC 21 8239

SCNNlA-4391 - UGAUGACACCCCCAUUCUUUCC 22 8240

SCNNlA-4392 - UUGAUGACACCCCCAUUCUUUCC 23 8241

SCNNlA-4393 - CUUGAUGACACCCCCAUUCUUUCC 24 8242

SCNNlA-4394 - GUGGAGACCUCCAUCAGC 18 8243

1299

5535.1 SCNNlA-4395 - CGUGGAGACCUCCAUCAGC 19 8244

SCNNlA-4396 - GCGUGGAGACCUCCAUCAGC 20 8245

SCNNlA-4397 - GGCGUGGAGACCUCCAUCAGC 21 8246

SCNNlA-4398 - UGGCGUGGAGACCUCCAUCAGC 22 8247

SCNNlA-4399 - CUGGCGUGGAGACCUCCAUCAGC 23 8248

SCNNlA-4400 - CCUGGCGUGGAGACCUCCAUCAGC 24 8249

SCNNlA-4401 - CGGAAAUUAAAGAGGAGC 18 8250

SCNNlA-4402 - CCGGAAAUUAAAGAGGAGC 19 8251

SCNNlA-1058 - CCCGGAAAUUAAAGAGGAGC 20 4907

SCNNlA-4403 - ACCCGGAAAUUAAAGAGGAGC 21 8252

SCNNlA-4404 - UACCCGGAAAUUAAAGAGGAGC 22 8253

SCNNlA-4405 - GUACCCGGAAAUUAAAGAGGAGC 23 8254

SCNNlA-4406 - GGUACCCGGAAAUUAAAGAGGAGC 24 8255

SCNNlA-4407 - CCGCACCCCUUGCAGCGC 18 8256

SCNNlA-4408 - GCCGCACCCCUUGCAGCGC 19 8257

SCNNlA-4409 - UGCCGCACCCCUUGCAGCGC 20 8258

SCNNlA-4410 - CUGCCGCACCCCUUGCAGCGC 21 8259

SCNNlA-4411 - UCUGCCGCACCCCUUGCAGCGC 22 8260

SCNNlA-4412 - CUCUGCCGCACCCCUUGCAGCGC 23 8261

SCNNlA-4413 - ACUCUGCCGCACCCCUUGCAGCGC 24 8262

SCNNlA-4414 - GGAUGCUGACUGGGAGGC 18 8263

SCNNlA-4415 - AGGAUGCUGACUGGGAGGC 19 8264

SCNNlA-4416 - AAGGAUGCUGACUGGGAGGC 20 8265

SCNNlA-4417 - CAAGGAUGCUGACUGGGAGGC 21 8266

SCNNlA-4418 - GCAAGGAUGCUGACUGGGAGGC 22 8267

SCNNlA-4419 - GGCAAGGAUGCUGACUGGGAGGC 23 8268

SCNNlA-4420 - AGGCAAGGAUGCUGACUGGGAGGC 24 8269

SCNNlA-4421 - UUUAACUUGCGGCCUGGC 18 8270

SCNNlA-4422 - CUUUAACUUGCGGCCUGGC 19 8271

SCNNlA-4423 - GCUUUAACUUGCGGCCUGGC 20 8272

SCNNlA-4424 - GGCUUUAACUUGCGGCCUGGC 21 8273

SCNNlA-4425 - UGGCUUUAACUUGCGGCCUGGC 22 8274

SCNNlA-4426 - GUGGCUUUAACUUGCGGCCUGGC 23 8275

SCNNlA-4427 - GGUGGCUUUAACUUGCGGCCUGGC 24 8276

SCNNlA-4428 - UCUGGAUGUCUUCCAUGC 18 8277

SCNNlA-4429 - CUCUGGAUGUCUUCCAUGC 19 8278

SCNNlA-4430 - CCUCUGGAUGUCUUCCAUGC 20 8279

SCNNlA-4431 - ACCUCUGGAUGUCUUCCAUGC 21 8280

SCNNlA-4432 - AACCUCUGGAUGUCUUCCAUGC 22 8281

SCNNlA-4433 - CAACCUCUGGAUGUCUUCCAUGC 23 8282

SCNNlA-4434 - CCAACCUCUGGAUGUCUUCCAUGC 24 8283

SCNNlA-4435 - GCAGCCGUCGCGACCUGC 18 8284

1300

5535.1 SCNNlA-4436 - CGCAGCCGUCGCGACCUGC 19 8285

SCNNlA-1079 - CCGCAGCCGUCGCGACCUGC 20 4928

SCNNlA-4437 - CCCGCAGCCGUCGCGACCUGC 21 8286

SCNNlA-4438 - UCCCGCAGCCGUCGCGACCUGC 22 8287

SCNNlA-4439 - CUCCCGCAGCCGUCGCGACCUGC 23 8288

SCNNlA-4440 - GCUCCCGCAGCCGUCGCGACCUGC 24 8289

SCNNlA-4441 - ACAUCCUGUCGAGGCUGC 18 8290

SCNNlA-4442 - AACAUCCUGUCGAGGCUGC 19 8291

SCNNlA-4443 - CAACAUCCUGUCGAGGCUGC 20 8292

SCNNlA-4444 - UCAACAUCCUGUCGAGGCUGC 21 8293

SCNNlA-4445 - AUCAACAUCCUGUCGAGGCUGC 22 8294

SCNNlA-4446 - CAUCAACAUCCUGUCGAGGCUGC 23 8295

SCNNlA-4447 - ACAUCAACAUCCUGUCGAGGCUGC 24 8296

SCNNlA-4448 - AUCUCCAGGGGGCUCUGC 18 8297

SCNNlA-4449 - CAUCUCCAGGGGGCUCUGC 19 8298

SCNNlA-1083 - CCAUCUCCAGGGGGCUCUGC 20 4932

SCNNlA-4450 - CCCAUCUCCAGGGGGCUCUGC 21 8299

SCNNlA-4451 - GCCCAUCUCCAGGGGGCUCUGC 22 8300

SCNNlA-4452 - CGCCCAUCUCCAGGGGGCUCUGC 23 8301

SCNNlA-4453 - CCGCCCAUCUCCAGGGGGCUCUGC 24 8302

SCNNlA-4454 - GGCUGUUUCACCAAGUGC 18 8303

SCNNlA-4455 - GGGCUGUUUCACCAAGUGC 19 8304

SCNNlA-1085 - UGGGCUGUUUCACCAAGUGC 20 4934

SCNNlA-4456 - CUGGGCUGUUUCACCAAGUGC 21 8305

SCNNlA-4457 - CCUGGGCUGUUUCACCAAGUGC 22 8306

SCNNlA-4458 - ACCUGGGCUGUUUCACCAAGUGC 23 8307

SCNNlA-4459 - CACCUGGGCUGUUUCACCAAGUGC 24 8308

SCNNlA-4460 - GGGCCCGGGUAAUGGUGC 18 8309

SCNNlA-4461 - GGGGCCCGGGUAAUGGUGC 19 8310

SCNNlA-4462 - UGGGGCCCGGGUAAUGGUGC 20 8311

SCNNlA-4463 - CUGGGGCCCGGGUAAUGGUGC 21 8312

SCNNlA-4464 - ACUGGGGCCCGGGUAAUGGUGC 22 8313

SCNNlA-4465 - GACUGGGGCCCGGGUAAUGGUGC 23 8314

SCNNlA-4466 - UGACUGGGGCCCGGGUAAUGGUGC 24 8315

SCNNlA-4467 - UUCCAGGAGAGCAUGAUC 18 8316

SCNNlA-4468 - CUUCCAGGAGAGCAUGAUC 19 8317

SCNNlA-4469 - GCUUCCAGGAGAGCAUGAUC 20 8318

SCNNlA-4470 - UGCUUCCAGGAGAGCAUGAUC 21 8319

SCNNlA-4471 - CUGCUUCCAGGAGAGCAUGAUC 22 8320

SCNNlA-4472 - CCUGCUUCCAGGAGAGCAUGAUC 23 8321

SCNNlA-4473 - UCCUGCUUCCAGGAGAGCAUGAUC 24 8322

SCNNlA-4474 - GUUCCUGGGGUGAGACUC 18 8323

1301

5535.1 SCNNlA-4475 - AGUUCCUGGGGUGAGACUC 19 8324

SCNNlA-4476 - CAGUUCCUGGGGUGAGACUC 20 8325

SCNNlA-4477 - ACAGUUCCUGGGGUGAGACUC 21 8326

SCNNlA-4478 - CACAGUUCCUGGGGUGAGACUC 22 8327

SCNNlA-4479 - GCACAGUUCCUGGGGUGAGACUC 23 8328

SCNNlA-4480 - AGCACAGUUCCUGGGGUGAGACUC 24 8329

SCNNlA-4481 - GGGUCCCGCCCCCGCCUC 18 8330

SCNNlA-4482 - AGGGUCCCGCCCCCGCCUC 19 8331

SCNNlA-4483 - GAGGGUCCCGCCCCCGCCUC 20 8332

SCNNlA-4484 - UGAGGGUCCCGCCCCCGCCUC 21 8333

SCNNlA-4485 - CUGAGGGUCCCGCCCCCGCCUC 22 8334

SCNNlA-4486 - CCUGAGGGUCCCGCCCCCGCCUC 23 8335

SCNNlA-4487 - GCCUGAGGGUCCCGCCCCCGCCUC 24 8336

SCNNlA-4488 - GUUCCUCCACCUGUCCUC 18 8337

SCNNlA-4489 - AGUUCCUCCACCUGUCCUC 19 8338

SCNNlA-1095 - CAGUUCCUCCACCUGUCCUC 20 4944

SCNNlA-4490 - CCAGUUCCUCCACCUGUCCUC 21 8339

SCNNlA-4491 - GCCAGUUCCUCCACCUGUCCUC 22 8340

SCNNlA-4492 - GGCCAGUUCCUCCACCUGUCCUC 23 8341

SCNNlA-4493 - GGGCCAGUUCCUCCACCUGUCCUC 24 8342

SCNNlA-4494 - GAGGGGGCAGGGGUGCUC 18 8343

SCNNlA-4495 - CGAGGGGGCAGGGGUGCUC 19 8344

SCNNlA-1096 - CCGAGGGGGCAGGGGUGCUC 20 4945

SCNNlA-4496 - GCCGAGGGGGCAGGGGUGCUC 21 8345

SCNNlA-4497 - GGCCGAGGGGGCAGGGGUGCUC 22 8346

SCNNlA-4498 - AGGCCGAGGGGGCAGGGGUGCUC 23 8347

SCNNlA-4499 - CAGGCCGAGGGGGCAGGGGUGCUC 24 8348

SCNNlA-4500 - UGGGCCCCCGCCCAUCUC 18 8349

SCNNlA-4501 - CUGGGCCCCCGCCCAUCUC 19 8350

SCNNlA-4502 - CCUGGGCCCCCGCCCAUCUC 20 8351

SCNNlA-4503 - CCCUGGGCCCCCGCCCAUCUC 21 8352

SCNNlA-4504 - ACCCUGGGCCCCCGCCCAUCUC 22 8353

SCNNlA-4505 - CACCCUGGGCCCCCGCCCAUCUC 23 8354

SCNNlA-4506 - CCACCCUGGGCCCCCGCCCAUCUC 24 8355

SCNNlA-4507 - UGUAUUCACUCCUGCUUC 18 8356

SCNNlA-4508 - GUGUAUUCACUCCUGCUUC 19 8357

SCNNlA-4509 - UGUGUAUUCACUCCUGCUUC 20 8358

SCNNlA-4510 - GUGUGUAUUCACUCCUGCUUC 21 8359

SCNNlA-4511 - GGUGUGUAUUCACUCCUGCUUC 22 8360

SCNNlA-4512 - AGGUGUGUAUUCACUCCUGCUUC 23 8361

SCNNlA-4513 - CAGGUGUGUAUUCACUCCUGCUUC 24 8362

SCNNlA-4514 - AAAGUCAACAUCUUCUUC 18 8363

1302

5535.1 SCNNlA-4515 - CAAAGUCAACAUCUUCUUC 19 8364

SCNNlA-4516 - CCAAAGUCAACAUCUUCUUC 20 8365

SCNNlA-4517 - GCCAAAGUCAACAUCUUCUUC 21 8366

SCNNlA-4518 - GGCCAAAGUCAACAUCUUCUUC 22 8367

SCNNlA-4519 - UGGCCAAAGUCAACAUCUUCUUC 23 8368

SCNNlA-4520 - GUGGCCAAAGUCAACAUCUUCUUC 24 8369

SCNNlA-4521 - CUACAGAAAGCACAGUUC 18 8370

SCNNlA-4522 - ACUACAGAAAG CACAG U U C 19 8371

SCNNlA-4523 - GACUACAGAAAGCACAGUUC 20 8372

SCNNlA-4524 - UGACUACAGAAAGCACAGUUC 21 8373

SCNNlA-4525 - G UG ACUACAGAAAG CACAG U U C 22 8374

SCNNlA-4526 - UGUGACUACAGAAAGCACAGUUC 23 8375

SCNNlA-4527 - CUGUGACUACAGAAAGCACAGUUC 24 8376

SCNNlA-4528 - GGUACCCGGAAAUUAAAG 18 8377

SCNNlA-4529 - AGG U ACCCGG AAAU UAAAG 19 8378

SCNNlA-1106 - CAGG U ACCCGG AAAU UAAAG 20 4955

SCNNlA-4530 - U CAGG U ACCCGG AAAU UAAAG 21 8379

SCNNlA-4531 - U U CAGG U ACCCGG AAAU UAAAG 22 8380

SCNNlA-4532 - CU U CAGG U ACCCGG AAAU UAAAG 23 8381

SCNNlA-4533 - CCUUCAGGUACCCGGAAAUUAAAG 24 8382

SCNNlA-4534 - GGGGCCCUGAGAGGGAAG 18 8383

SCNNlA-4535 - GGGGGCCCUGAGAGGGAAG 19 8384

SCNNlA-4536 - GGGGGGCCCUGAGAGGGAAG 20 8385

SCNNlA-4537 - GGGGGGGCCCUGAGAGGGAAG 21 8386

SCNNlA-4538 - UGGGGGGGCCCUGAGAGGGAAG 22 8387

SCNNlA-4539 - CUGGGGGGGCCCUGAGAGGGAAG 23 8388

SCNNlA-4540 - UCUGGGGGGGCCCUGAGAGGGAAG 24 8389

SCNNlA-4541 - CGGGACAACAACCCCCAG 18 8390

SCNNlA-4542 - GCGGGACAACAACCCCCAG 19 8391

SCNNlA-4543 - UGCGGGACAACAACCCCCAG 20 8392

SCNNlA-4544 - UUGCGGGACAACAACCCCCAG 21 8393

SCNNlA-4545 - CUUGCGGGACAACAACCCCCAG 22 8394

SCNNlA-4546 - GCUUGCGGGACAACAACCCCCAG 23 8395

SCNNlA-4547 - AGCUUGCGGGACAACAACCCCCAG 24 8396

SCNNlA-4548 - UCCAACCUGGGCAGCCAG 18 8397

SCNNlA-4549 - GUCCAACCUGGGCAGCCAG 19 8398

SCNNlA-1116 - UGUCCAACCUGGGCAGCCAG 20 4965

SCNNlA-4550 - CUGUCCAACCUGGGCAGCCAG 21 8399

SCNNlA-4551 - CCUGUCCAACCUGGGCAGCCAG 22 8400

SCNNlA-4552 - UCCUGUCCAACCUGGGCAGCCAG 23 8401

SCNNlA-4553 - CUCCUGUCCAACCUGGGCAGCCAG 24 8402

SCNNlA-4554 - AUUCACUCCUGCUUCCAG 18 8403

1303

5535.1 SCNNlA-4555 - UAUUCACUCCUGCUUCCAG 19 8404

SCNNlA-4556 - GUAUUCACUCCUGCUUCCAG 20 8405

SCNNlA-4557 - UGUAUUCACUCCUGCUUCCAG 21 8406

SCNNlA-4558 - GUGUAUUCACUCCUGCUUCCAG 22 8407

SCNNlA-4559 - UGUGUAUUCACUCCUGCUUCCAG 23 8408

SCNNlA-4560 - GUGUGUAUUCACUCCUGCUUCCAG 24 8409

SCNNlA-4561 - U CAAAG U ACAC ACAG CAG 18 8410

SCNNlA-4562 - U U CAAAG U ACACACAG CAG 19 8411

SCNNlA-4563 - C U U CAAAG U ACAC ACAG CAG 20 8412

SCNNlA-4564 - CCU U CAAAG U ACACACAG CAG 21 8413

SCNNlA-4565 - CCCU U CAAAG U ACACACAGCAG 22 8414

SCNNlA-4566 - ACCCU U CAAAG U ACACACAGCAG 23 8415

SCNNlA-4567 - U ACCCU U CAAAG U ACACACAG CAG 24 8416

SCNNlA-4568 - AACAUCUUCUUCAAGGAG 18 8417

SCNNlA-4569 - CAACAUCUUCUUCAAGGAG 19 8418

SCNNlA-4570 - UCAACAUCUUCUUCAAGGAG 20 8419

SCNNlA-4571 - GUCAACAUCUUCUUCAAGGAG 21 8420

SCNNlA-4572 - AGUCAACAUCUUCUUCAAGGAG 22 8421

SCNNlA-4573 - AAGUCAACAUCUUCUUCAAGGAG 23 8422

SCNNlA-4574 - AAAG U CAAC AU CU U C U U CAAG GAG 24 8423

SCNNlA-4575 - CCGGAAAU U AAAG AGG AG 18 8424

SCNNlA-4576 - CCCGG AAAU U AAAG AGG AG 19 8425

SCNNlA-4577 - ACCCGGAAAUUAAAGAGGAG 20 8426

SCNNlA-4578 - U ACCCGG AAAU U AAAG AGG AG 21 8427

SCNNlA-4579 - GUACCCGGAAAUUAAAGAGGAG 22 8428

SCNNlA-4580 - GGU ACCCGGAAAUUAAAGAGGAG 23 8429

SCNNlA-4581 - AGGUACCCGGAAAUUAAAGAGGAG 24 8430

SCNNlA-4582 - AAAGAGGAGCUGGAGGAG 18 8431

SCNNlA-4583 - UAAAGAGGAGCUGGAGGAG 19 8432

SCNNlA-4584 - UUAAAGAGGAGCUGGAGGAG 20 8433

SCNNlA-4585 - AUUAAAGAGGAGCUGGAGGAG 21 8434

SCNNlA-4586 - AAUUAAAGAGGAGCUGGAGGAG 22 8435

SCNNlA-4587 - AAAUUAAAGAGGAGCUGGAGGAG 23 8436

SCNNlA-4588 - GAAAUUAAAGAGGAGCUGGAGGAG 24 8437

SCNNlA-4589 - ACUCUGCCAUCCCUGGAG 18 8438

SCNNlA-4590 - GACUCUGCCAUCCCUGGAG 19 8439

SCNNlA-4591 - AGACUCUGCCAUCCCUGGAG 20 8440

SCNNlA-4592 - GAGACUCUGCCAUCCCUGGAG 21 8441

SCNNlA-4593 - AGAGACUCUGCCAUCCCUGGAG 22 8442

SCNNlA-4594 - CAGAGACUCUGCCAUCCCUGGAG 23 8443

SCNNlA-4595 - CCAGAGACUCUGCCAUCCCUGGAG 24 8444

SCNNlA-4596 - CUCUGGGGGGGCCCUGAG 18 8445

1304

5535.1 SCNNlA-4597 - CCUCUGGGGGGGCCCUGAG 19 8446

SCNNlA-1140 - UCCUCUGGGGGGGCCCUGAG 20 4989

SCNNlA-4598 - GUCCUCUGGGGGGGCCCUGAG 21 8447

SCNNlA-4599 - UGUCCUCUGGGGGGGCCCUGAG 22 8448

SCNNlA-4600 - CUGUCCUCUGGGGGGGCCCUGAG 23 8449

SCNNlA-4601 - CCUGUCCUCUGGGGGGGCCCUGAG 24 8450

SCNNlA-4602 - UGCCUGGAAUCAACAACG 18 8451

SCNNlA-4603 - AUGCCUGGAAUCAACAACG 19 8452

SCNNlA-4604 - CAUGCCUGGAAUCAACAACG 20 8453

SCNNlA-4605 - CCAUGCCUGGAAUCAACAACG 21 8454

SCNNlA-4606 - UCCAUGCCUGGAAUCAACAACG 22 8455

SCNNlA-4607 - UUCCAUGCCUGGAAUCAACAACG 23 8456

SCNNlA-4608 - CUUCCAUGCCUGGAAUCAACAACG 24 8457

SCNNlA-4609 - UCCCUGGAGGAGGACACG 18 8458

SCNNlA-4610 - AUCCCUGGAGGAGGACACG 19 8459

SCNNlA-4611 - CAUCCCUGGAGGAGGACACG 20 8460

SCNNlA-4612 - CCAUCCCUGGAGGAGGACACG 21 8461

SCNNlA-4613 - GCCAUCCCUGGAGGAGGACACG 22 8462

SCNNlA-4614 - UGCCAUCCCUGGAGGAGGACACG 23 8463

SCNNlA-4615 - CUGCCAUCCCUGGAGGAGGACACG 24 8464

SCNNlA-4616 - CCCGCCUCACGGGGCCCG 18 8465

SCNNlA-4617 - CCCCGCCUCACGGGGCCCG 19 8466

SCNNlA-4618 - CCCCCGCCUCACGGGGCCCG 20 8467

SCNNlA-4619 - GCCCCCGCCUCACGGGGCCCG 21 8468

SCNNlA-4620 - CGCCCCCGCCUCACGGGGCCCG 22 8469

SCNNlA-4621 - CCGCCCCCGCCUCACGGGGCCCG 23 8470

SCNNlA-4622 - CCCGCCCCCGCCUCACGGGGCCCG 24 8471

SCNNlA-4623 - GUGAGGCCCGCAGCGCCG 18 8472

SCNNlA-4624 - GGUGAGGCCCGCAGCGCCG 19 8473

SCNNlA-1148 - UGGUGAGGCCCGCAGCGCCG 20 4997

SCNNlA-4625 - CUGGUGAGGCCCGCAGCGCCG 21 8474

SCNNlA-4626 - GCUGGUGAGGCCCGCAGCGCCG 22 8475

SCNNlA-4627 - AGCUGGUGAGGCCCGCAGCGCCG 23 8476

SCNNlA-4628 - CAGCUGGUGAGGCCCGCAGCGCCG 24 8477

SCNNlA-4629 - AUACUGGUCUCCAGGCCG 18 8478

SCNNlA-4630 - GAUACUGGUCUCCAGGCCG 19 8479

SCNNlA-1149 - CGAUACUGGUCUCCAGGCCG 20 4998

SCNNlA-4631 - CCGAUACUGGUCUCCAGGCCG 21 8480

SCNNlA-4632 - GCCGAUACUGGUCUCCAGGCCG 22 8481

SCNNlA-4633 - AGCCGAUACUGGUCUCCAGGCCG 23 8482

SCNNlA-4634 - AAGCCGAUACUGGUCUCCAGGCCG 24 8483

SCNNlA-4635 - CUGGUGAGGCCCGCAGCG 18 8484

1305

5535.1 SCNNlA-4636 - GCUGGUGAGGCCCGCAGCG 19 8485

SCNNlA-4637 - AGCUGGUGAGGCCCGCAGCG 20 8486

SCNNlA-4638 - CAGCUGGUGAGGCCCGCAGCG 21 8487

SCNNlA-4639 - CCAGCUGGUGAGGCCCGCAGCG 22 8488

SCNNlA-4640 - UCCAGCUGGUGAGGCCCGCAGCG 23 8489

SCNNlA-4641 - UUCCAGCUGGUGAGGCCCGCAGCG 24 8490

SCNNlA-4642 - UGUCCCUGAUGCUGCGCG 18 8491

SCNNlA-4643 - CUGUCCCUGAUGCUGCGCG 19 8492

SCNNlA-4644 - UCUGUCCCUGAUGCUGCGCG 20 8493

SCNNlA-4645 - GUCUGUCCCUGAUGCUGCGCG 21 8494

SCNNlA-4646 - GGUCUGUCCCUGAUGCUGCGCG 22 8495

SCNNlA-4647 - AGGUCUGUCCCUGAUGCUGCGCG 23 8496

SCNNlA-4648 - UAGGUCUGUCCCUGAUGCUGCGCG 24 8497

SCNNlA-4649 - UUAACUUGCGGCCUGGCG 18 8498

SCNNlA-4650 - UUUAACUUGCGGCCUGGCG 19 8499

SCNNlA-1157 - CUUUAACUUGCGGCCUGGCG 20 5006

SCNNlA-4651 - GCUUUAACUUGCGGCCUGGCG 21 8500

SCNNlA-4652 - GGCUUUAACUUGCGGCCUGGCG 22 8501

SCNNlA-4653 - UGGCUUUAACUUGCGGCCUGGCG 23 8502

SCNNlA-4654 - GUGGCUUUAACUUGCGGCCUGGCG 24 8503

SCNNlA-4655 - UCAUCAGGGGUGGAUGCG 18 8504

SCNNlA-4656 - CUCAUCAGGGGUGGAUGCG 19 8505

SCNNlA-4657 - ACUCAUCAGGGGUGGAUGCG 20 8506

SCNNlA-4658 - UACUCAUCAGGGGUGGAUGCG 21 8507

SCNNlA-4659 - AUACUCAUCAGGGGUGGAUGCG 22 8508

SCNNlA-4660 - CAUACUCAUCAGGGGUGGAUGCG 23 8509

SCNNlA-4661 - ACAUACUCAUCAGGGGUGGAUGCG 24 8510

SCNNlA-4662 - CAGCCGUCGCGACCUGCG 18 8511

SCNNlA-4663 - GCAGCCGUCGCGACCUGCG 19 8512

SCNNlA-1158 - CGCAGCCGUCGCGACCUGCG 20 5007

SCNNlA-4664 - CCGCAGCCGUCGCGACCUGCG 21 8513

SCNNlA-4665 - CCCGCAGCCGUCGCGACCUGCG 22 8514

SCNNlA-4666 - UCCCGCAGCCGUCGCGACCUGCG 23 8515

SCNNlA-4667 - CUCCCGCAGCCGUCGCGACCUGCG 24 8516

SCNNlA-4668 - CCGAUACUGGUCUCCAGG 18 8517

SCNNlA-4669 - GCCGAUACUGGUCUCCAGG 19 8518

SCNNlA-4670 - AGCCGAUACUGGUCUCCAGG 20 8519

SCNNlA-4671 - AAGCCGAUACUGGUCUCCAGG 21 8520

SCNNlA-4672 - GAAGCCGAUACUGGUCUCCAGG 22 8521

SCNNlA-4673 - CGAAGCCGAUACUGGUCUCCAGG 23 8522

SCNNlA-4674 - CCGAAGCCGAUACUGGUCUCCAGG 24 8523

SCNNlA-4675 - UAAUGGUGCACGGGCAGG 18 8524

1306

5535.1 SCNNlA-4676 - GUAAUGGUGCACGGGCAGG 19 8525

SCNNlA-4677 - GGUAAUGGUGCACGGGCAGG 20 8526

SCNNlA-4678 - GGGUAAUGGUGCACGGGCAGG 21 8527

SCNNlA-4679 - CGGGUAAUGGUGCACGGGCAGG 22 8528

SCNNlA-4680 - CCGGGUAAUGGUGCACGGGCAGG 23 8529

SCNNlA-4681 - CCCGGGUAAUGGUGCACGGGCAGG 24 8530

SCNNlA-4682 - GGGGGGGCCCUGAGAGGG 18 8531

SCNNlA-4683 - UGGGGGGGCCCUGAGAGGG 19 8532

SCNNlA-4684 - CUGGGGGGGCCCUGAGAGGG 20 8533

SCNNlA-4685 - UCUGGGGGGGCCCUGAGAGGG 21 8534

SCNNlA-4686 - CUCUGGGGGGGCCCUGAGAGGG 22 8535

SCNNlA-4687 - CCUCUGGGGGGGCCCUGAGAGGG 23 8536

SCNNlA-4688 - UCCUCUGGGGGGGCCCUGAGAGGG 24 8537

SCNNlA-4689 - GUCUCCAGGCCGAGGGGG 18 8538

SCNNlA-4690 - GGUCUCCAGGCCGAGGGGG 19 8539

SCNNlA-4691 - UGGUCUCCAGGCCGAGGGGG 20 8540

SCNNlA-4692 - CUGGUCUCCAGGCCGAGGGGG 21 8541

SCNNlA-4693 - ACUGGUCUCCAGGCCGAGGGGG 22 8542

SCNNlA-4694 - UACUGGUCUCCAGGCCGAGGGGG 23 8543

SCNNlA-4695 - AUACUGGUCUCCAGGCCGAGGGGG 24 8544

SCNNlA-4696 - CCCAGGUAGAGUGUGGGG 18 8545

SCNNlA-4697 - UCCCAGGUAGAGUGUGGGG 19 8546

SCNNlA-4698 - AUCCCAGGUAGAGUGUGGGG 20 8547

SCNNlA-4699 - CAUCCCAGGUAGAGUGUGGGG 21 8548

SCNNlA-4700 - ACAUCCCAGGUAGAGUGUGGGG 22 8549

SCNNlA-4701 - GACAUCCCAGGUAGAGUGUGGGG 23 8550

SCNNlA-4702 - UGACAUCCCAGGUAGAGUGUGGGG 24 8551

SCNNlA-4703 - GUGUGGGGAAGGGAUGGG 18 8552

SCNNlA-4704 - AGUGUGGGGAAGGGAUGGG 19 8553

SCNNlA-1189 - GAGUGUGGGGAAGGGAUGGG 20 5038

SCNNlA-4705 - AGAGUGUGGGGAAGGGAUGGG 21 8554

SCNNlA-4706 - UAGAGUGUGGGGAAGGGAUGGG 22 8555

SCNNlA-4707 - GUAGAGUGUGGGGAAGGGAUGGG 23 8556

SCNNlA-4708 - GGUAGAGUGUGGGGAAGGGAUGGG 24

8557

SCNNlA-4709 - GAAAGCACAGUUCCUGGG 18 8558

SCNNlA-4710 - AGAAAGCACAGUUCCUGGG 19 8559

SCNNlA-4711 - CAGAAAGCACAGUUCCUGGG 20 8560

SCNNlA-4712 - ACAGAAAGCACAGUUCCUGGG 21 8561

SCNNlA-4713 - UACAGAAAGCACAGUUCCUGGG 22 8562

SCNNlA-4714 - CUACAGAAAGCACAGUUCCUGGG 23 8563

SCNNlA-4715 - ACUACAGAAAGCACAGUUCCUGGG 24 8564

1307

5535.1 SCNNlA-4716 - UGUCUGUGGUGGAGAUGG 18 8565

SCNNlA-4717 - UUGUCUGUGGUGGAGAUGG 19 8566

SCNNlA-4718 - GUUGUCUGUGGUGGAGAUGG 20 8567

SCNNlA-4719 - UGUUGUCUGUGGUGGAGAUGG 21 8568

SCNNlA-4720 - GUGUUGUCUGUGGUGGAGAUGG 22 8569

SCNNlA-4721 - GGUGUUGUCUGUGGUGGAGAUGG 23 8570

SCNNlA-4722 - CGGUGUUGUCUGUGGUGGAGAUGG 24

8571

SCNNlA-4723 - AGUGUGGGGAAGGGAUGG 18 8572

SCNNlA-4724 - GAGUGUGGGGAAGGGAUGG 19 8573

SCNNlA-4725 - AGAGUGUGGGGAAGGGAUGG 20 8574

SCNNlA-4726 - UAGAGUGUGGGGAAGGGAUGG 21 8575

SCNNlA-4727 - GUAGAGUGUGGGGAAGGGAUGG 22 8576

SCNNlA-4728 - GGUAGAGUGUGGGGAAGGGAUGG 23 8577

SCNNlA-4729 - AGGUAGAGUGUGGGGAAGGGAUGG 24

8578

SCNNlA-4730 - AACCCCCAGGUGGACUGG 18 8579

SCNNlA-4731 - CAACCCCCAGGUGGACUGG 19 8580

SCNNlA-4732 - ACAACCCCCAGGUGGACUGG 20 8581

SCNNlA-4733 - AACAACCCCCAGGUGGACUGG 21 8582

SCNNlA-4734 - CAACAACCCCCAGGUGGACUGG 22 8583

SCNNlA-4735 - ACAACAACCCCCAGGUGGACUGG 23 8584

SCNNlA-4736 - GACAA CAACCCCCAGGUGGACUGG 24 8585

SCNNlA-4737 - AGACUCUGCCAUCCCUGG 18 8586

SCNNlA-4738 - GAGACUCUGCCAUCCCUGG 19 8587

SCNNlA-1196 - AGAGACUCUGCCAUCCCUGG 20 5045

SCNNlA-4739 - CAGAGACUCUGCCAUCCCUGG 21 8588

SCNNlA-4740 - CCAGAGACUCUGCCAUCCCUGG 22 8589

SCNNlA-4741 - GCCAGAGACUCUGCCAUCCCUGG 23 8590

SCNNlA-4742 - UGCCAGAGACUCUGCCAUCCCUGG 24 8591

SCNNlA-4743 - ACGGUAGGUCGUGCCUGG 18 8592

SCNNlA-4744 - CACGGUAGGUCGUGCCUGG 19 8593

SCNNlA-4745 - UCACGGUAGGUCGUGCCUGG 20 8594

SCNNlA-4746 - GUCACGGUAGGUCGUGCCUGG 21 8595

SCNNlA-4747 - UGUCACGGUAGGUCGUGCCUGG 22 8596

SCNNlA-4748 - CUGUCACGGUAGGUCGUGCCUGG 23 8597

SCNNlA-4749 - UCUGUCACGGUAGGUCGUGCCUGG 24 8598

SCNNlA-4750 - AAAUUAAAGAGGAGCUGG 18 8599

SCNNlA-4751 - GAAAUUAAAGAGGAGCUGG 19 8600

SCNNlA-1198 - GGAAAUUAAAGAGGAGCUGG 20 5047

SCNNlA-4752 - CGGAAAUUAAAGAGGAGCUGG 21 8601

SCNNlA-4753 - CCGGAAAUUAAAGAGGAGCUGG 22 8602

1308

5535.1 SCNNlA-4754 - CCCGGAAAUUAAAGAGGAGCUGG 23 8603

SCNNlA-4755 - ACCCGGAAAUUAAAGAGGAGCUGG 24 8604

SCNNlA-4756 - CCUCCACCUGUCCUCUGG 18 8605

SCNNlA-4757 - UCCUCCACCUGUCCUCUGG 19 8606

SCNNlA-1199 - UUCCUCCACCUGUCCUCUGG 20 5048

SCNNlA-4758 - GUUCCUCCACCUGUCCUCUGG 21 8607

SCNNlA-4759 - AGUUCCUCCACCUGUCCUCUGG 22 8608

SCNNlA-4760 - CAGUUCCUCCACCUGUCCUCUGG 23 8609

SCNNlA-4761 - CCAGUUCCUCCACCUGUCCUCUGG 24 8610

SCNNlA-4762 - CCUCGGUGUUGUCUGUGG 18 8611

SCNNlA-4763 - UCCUCGGUGUUGUCUGUGG 19 8612

SCNNlA-1205 - CUCCUCGGUGUUGUCUGUGG 20 5054

SCNNlA-4764 - GCUCCUCGGUGUUGUCUGUGG 21 8613

SCNNlA-4765 - GGCUCCUCGGUGUUGUCUGUGG 22 8614

SCNNlA-4766 - CGGCUCCUCGGUGUUGUCUGUGG 23 8615

SCNNlA-4767 - UCGGCUCCUCGGUGUUGUCUGUGG 24 8616

SCNNlA-4768 - GAGACCUCCAUCAGCAUG 18 8617

SCNNlA-4769 - GGAGACCUCCAUCAGCAUG 19 8618

SCNNlA-1210 - UGGAGACCUCCAUCAGCAUG 20 5059

SCNNlA-4770 - GUGGAGACCUCCAUCAGCAUG 21 8619

SCNNlA-4771 - CGUGGAGACCUCCAUCAGCAUG 22 8620

SCNNlA-4772 - GCGUGGAGACCUCCAUCAGCAUG 23 8621

SCNNlA-4773 - GGCGUGGAGACCUCCAUCAGCAUG 24 8622

SCNNlA-4774 - CGCAGCCGUCGCGACCUG 18 8623

SCNNlA-4775 - CCGCAGCCGUCGCGACCUG 19 8624

SCNNlA-1216 - CCCGCAGCCGUCGCGACCUG 20 5065

SCNNlA-4776 - UCCCGCAGCCGUCGCGACCUG 21 8625

SCNNlA-4777 - CUCCCGCAGCCGUCGCGACCUG 22 8626

SCNNlA-4778 - GCUCCCGCAGCCGUCGCGACCUG 23 8627

SCNNlA-4779 - GGCUCCCGCAGCCGUCGCGACCUG 24 8628

SCNNlA-4780 - GAGACUCUGCCAUCCCUG 18 8629

SCNNlA-4781 - AGAGACUCUGCCAUCCCUG 19 8630

SCNNlA-4782 - CAGAGACUCUGCCAUCCCUG 20 8631

SCNNlA-4783 - CCAGAGACUCUGCCAUCCCUG 21 8632

SCNNlA-4784 - GCCAGAGACUCUGCCAUCCCUG 22 8633

SCNNlA-4785 - UGCCAGAGACUCUGCCAUCCCUG 23 8634

SCNNlA-4786 - CUGCCAGAGACUCUGCCAUCCCUG 24 8635

SCNNlA-4787 - CACUACAUCAACAUCCUG 18 8636

SCNNlA-4788 - CCACUACAUCAACAUCCUG 19 8637

SCNNlA-4789 - UCCACUACAUCAACAUCCUG 20 8638

SCNNlA-4790 - UUCCACUACAUCAACAUCCUG 21 8639

SCNNlA-4791 - CUUCCACUACAUCAACAUCCUG 22 8640

1309

5535.1 SCNNlA-4792 - GCUUCCACUACAUCAACAUCCUG 23 8641

SCNNlA-4793 - CGCUUCCACUACAUCAACAUCCUG 24 8642

SCNNlA-4794 - AUGGCAGUGAUGUUCCUG 18 8643

SCNNlA-4795 - AAUGGCAGUGAUGUUCCUG 19 8644

SCNNlA-4796 - GAAUGGCAGUGAUGUUCCUG 20 8645

SCNNlA-4797 - AGAAUGGCAGUGAUGUUCCUG 21 8646

SCNNlA-4798 - AAGAAUGGCAGUGAUGUUCCUG 22 8647

SCNNlA-4799 - CAAGAAUGGCAGUGAUGUUCCUG 23 8648

SCNNlA-4800 - CCAAGAAUGGCAGUGAUGUUCCUG 24 8649

SCNNlA-4801 - AAGAUCGGCUUCCAGCUG 18 8650

SCNNlA-4802 - GAAGAUCGGCUUCCAGCUG 19 8651

SCNNlA-4803 - GGAAGAUCGGCUUCCAGCUG 20 8652

SCNNlA-4804 - UGGAAGAUCGGCUUCCAGCUG 21 8653

SCNNlA-4805 - CUGGAAGAUCGGCUUCCAGCUG 22 8654

SCNNlA-4806 - ACUGGAAGAUCGGCUUCCAGCUG 23 8655

SCNNlA-4807 - GACUGGAAGAUCGGCUUCCAGCUG 24 8656

SCNNlA-4808 - GAAAUUAAAGAGGAGCUG 18 8657

SCNNlA-4809 - GGAAAUUAAAGAGGAGCUG 19 8658

SCNNlA-4810 - CGGAAAUUAAAGAGGAGCUG 20 8659

SCNNlA-4811 - CCGGAAAUUAAAGAGGAGCUG 21 8660

SCNNlA-4812 - CCCGGAAAUUAAAGAGGAGCUG 22 8661

SCNNlA-4813 - ACCCGGAAAUUAAAGAGGAGCUG 23 8662

SCNNlA-4814 - UACCCGGAAAUUAAAGAGGAGCUG 24 8663

SCNNlA-4815 - UCCUCCACCUGUCCUCUG 18 8664

SCNNlA-4816 - UUCCUCCACCUGUCCUCUG 19 8665

SCNNlA-1224 - GUUCCUCCACCUGUCCUCUG 20 5073

SCNNlA-4817 - AGUUCCUCCACCUGUCCUCUG 21 8666

SCNNlA-4818 - CAGUUCCUCCACCUGUCCUCUG 22 8667

SCNNlA-4819 - CCAGUUCCUCCACCUGUCCUCUG 23 8668

SCNNlA-4820 - GCCAGUUCCUCCACCUGUCCUCUG 24 8669

SCNNlA-4821 - CAUCUCCAGGGGGCUCUG 18 8670

SCNNlA-4822 - CCAUCUCCAGGGGGCUCUG 19 8671

SCNNlA-4823 - CCCAUCUCCAGGGGGCUCUG 20 8672

SCNNlA-4824 - GCCCAUCUCCAGGGGGCUCUG 21 8673

SCNNlA-4825 - CGCCCAUCUCCAGGGGGCUCUG 22 8674

SCNNlA-4826 - CCGCCCAUCUCCAGGGGGCUCUG 23 8675

SCNNlA-4827 - CCCGCCCAUCUCCAGGGGGCUCUG 24 8676

SCNNlA-4828 - GGGCUGUUUCACCAAGUG 18 8677

SCNNlA-4829 - UGGGCUGUUUCACCAAGUG 19 8678

SCNNlA-4830 - CUGGGCUGUUUCACCAAGUG 20 8679

SCNNlA-4831 - CCUGGGCUGUUUCACCAAGUG 21 8680

SCNNlA-4832 - ACCUGGGCUGUUUCACCAAGUG 22 8681

1310

5535.1 SCNNlA-4833 - CACCUGGGCUGUUUCACCAAGUG 23 8682

SCNNlA-4834 - CCACCUGGGCUGUUUCACCAAGUG 24 8683

SCNNlA-4835 - GACAUCCCAGGUAGAGUG 18 8684

SCNNlA-4836 - UGACAUCCCAGGUAGAGUG 19 8685

SCNNlA-1228 - GUGACAUCCCAGGUAGAGUG 20 5077

SCNNlA-4837 - GGUGACAUCCCAGGUAGAGUG 21 8686

SCNNlA-4838 - CGGUGACAUCCCAGGUAGAGUG 22 8687

SCNNlA-4839 - UCGGUGACAUCCCAGGUAGAGUG 23 8688

SCNNlA-4840 - CUCGGUGACAUCCCAGGUAGAGUG 24 8689

SCNNlA-4841 - UCAGGGGUGGAUGCGGUG 18 8690

SCNNlA-4842 - AUCAGGGGUGGAUGCGGUG 19 8691

SCNNlA-1233 - CAUCAGGGGUGGAUGCGGUG 20 5082

SCNNlA-4843 - UCAUCAGGGGUGGAUGCGGUG 21 8692

SCNNlA-4844 - CUCAUCAGGGGUGGAUGCGGUG 22 8693

SCNNlA-4845 - ACUCAUCAGGGGUGGAUGCGGUG 23 8694

SCNNlA-4846 - UACUCAUCAGGGGUGGAUGCGGUG 24 8695

SCNNlA-4847 - UCCUCGGUGUUGUCUGUG 18 8696

SCNNlA-4848 - CUCCUCGGUGUUGUCUGUG 19 8697

SCNNlA-4849 - GCUCCUCGGUGUUGUCUGUG 20 8698

SCNNlA-4850 - GGCUCCUCGGUGUUGUCUGUG 21 8699

SCNNlA-4851 - CGGCUCCUCGGUGUUGUCUGUG 22 8700

SCNNlA-4852 - UCGGCUCCUCGGUGUUGUCUGUG 23 8701

SCNNlA-4853 - UUCGGCUCCUCGGUGUUGUCUGUG 24 8702

SCNNlA-4854 - CAUCCCAGGUAGAGUGUG 18 8703

SCNNlA-4855 - ACAUCCCAGGUAGAGUGUG 19 8704

SCNNlA-1238 - GACAUCCCAGGUAGAGUGUG 20 5087

SCNNlA-4856 - UGACAUCCCAGGUAGAGUGUG 21 8705

SCNNlA-4857 - GUGACAUCCCAGGUAGAGUGUG 22 8706

SCNNlA-4858 - GGUGACAUCCCAGGUAGAGUGUG 23 8707

SCNNlA-4859 - CGGUGACAUCCCAGGUAGAGUGUG 24 8708

SCNNlA-4860 - AGCGUGGCCUCCAGCUUG 18 8709

SCNNlA-4861 - UAGCGUGGCCUCCAGCUUG 19 8710

SCNNlA-1242 - GUAGCGUGGCCUCCAGCUUG 20 5091

SCNNlA-4862 - CGUAGCGUGGCCUCCAGCUUG 21 8711

SCNNlA-4863 - CCGUAGCGUGGCCUCCAGCUUG 22 8712

SCNNlA-4864 - CCCGUAGCGUGGCCUCCAGCUUG 23 8713

SCNNlA-4865 - GCCCGUAGCGUGGCCUCCAGCUUG 24 8714

SCNNlA-4866 - GGAGACCUCCAUCAGCAU 18 8715

SCNNlA-4867 - UGGAGACCUCCAUCAGCAU 19 8716

SCNNlA-4868 - GUGGAGACCUCCAUCAGCAU 20 8717

SCNNlA-4869 - CGUGGAGACCUCCAUCAGCAU 21 8718

SCNNlA-4870 - GCGUGGAGACCUCCAUCAGCAU 22 8719

1311

5535.1 SCNNlA-4871 - GGCGUGGAGACCUCCAUCAGCAU 23 8720

SCNNlA-4872 - UGGCGUGGAGACCUCCAUCAGCAU 24 8721

SCNNlA-4873 - UCUACCAGACAUACUCAU 18 8722

SCNNlA-4874 - UUCUACCAGACAUACUCAU 19 8723

SCNNlA-4875 - CUUCUACCAGACAUACUCAU 20 8724

SCNNlA-4876 - GCUUCUACCAGACAUACUCAU 21 8725

SCNNlA-4877 - UGCUUCUACCAGACAUACUCAU 22 8726

SCNNlA-4878 - CUGCUUCUACCAGACAUACUCAU 23 8727

SCNNlA-4879 - ACUGCUUCUACCAGACAUACUCAU 24 8728

SCNNlA-4880 - UGGUGUAUGUGGGUUCAU 18 8729

SCNNlA-4881 - UUGGUGUAUGUGGGUUCAU 19 8730

SCNNlA-1250 - CUUGGUGUAUGUGGGUUCAU 20 5099

SCNNlA-4882 - UCUUGGUGUAUGUGGGUUCAU 21 8731

SCNNlA-4883 - CUCUUGGUGUAUGUGGGUUCAU 22 8732

SCNNlA-4884 - UCUCUUGGUGUAUGUGGGUUCAU 23 8733

SCNNlA-4885 - AUCUCUUGGUGUAUGUGGGUUCAU 24

8734

SCNNlA-4886 - UACUCUCUCUUUCCUGAU 18 8735

SCNNlA-4887 - CUACUCUCUCUUUCCUGAU 19 8736

SCNNlA-4888 - CCUACUCUCUCUUUCCUGAU 20 8737

SCNNlA-4889 - CCCUACUCUCUCUUUCCUGAU 21 8738

SCNNlA-4890 - ACCCUACUCUCUCUUUCCUGAU 22 8739

SCNNlA-4891 - GACCCUACUCUCUCUUUCCUGAU 23 8740

SCNNlA-4892 - UGACCCUACUCUCUCUUUCCUGAU 24 8741

SCNNlA-4893 - GGAAACCCUGGACAGACU 18 8742

SCNNlA-4894 - AGGAAACCCUGGACAGACU 19 8743

SCNNlA-1257 - UAGGAAACCCUGGACAGACU 20 5106

SCNNlA-4895 - AUAGGAAACCCUGGACAGACU 21 8744

SCNNlA-4896 - CAUAGGAAACCCUGGACAGACU 22 8745

SCNNlA-4897 - UCAUAGGAAACCCUGGACAGACU 23 8746

SCNNlA-4898 - UUCAUAGGAAACCCUGGACAGACU 24 8747

SCNNlA-4899 - AAGGCAAGGAUGCUGACU 18 8748

SCNNlA-4900 - GAAGGCAAGGAUGCUGACU 19 8749

SCNNlA-1258 - GGAAGGCAAGGAUGCUGACU 20 5107

SCNNlA-4901 - AGGAAGGCAAGGAUGCUGACU 21 8750

SCNNlA-4902 - GAGGAAGGCAAGGAUGCUGACU 22 8751

SCNNlA-4903 - UGAGGAAGGCAAGGAUGCUGACU 23 8752

SCNNlA-4904 - AUGAGGAAGGCAAGGAUGCUGACU 24 8753

SCNNlA-4905 - ACCCUCUGCCCCACACCU 18 8754

SCNNlA-4906 - CACCCUCUGCCCCACACCU 19 8755

SCNNlA-4907 - CCACCCUCUGCCCCACACCU 20 8756

SCNNlA-4908 - CCCACCCUCUGCCCCACACCU 21 8757

1312

5535.1 SCNNlA-4909 - UCCCACCCUCUGCCCCACACCU 22 8758

SCNNlA-4910 - UUCCCACCCUCUGCCCCACACCU 23 8759

SCNNlA-4911 - CUUCCCACCCUCUGCCCCACACCU 24 8760

SCNNlA-4912 - CCGCAGCCGUCGCGACCU 18 8761

SCNNlA-4913 - CCCGCAGCCGUCGCGACCU 19 8762

SCNNlA-4914 - UCCCGCAGCCGUCGCGACCU 20 8763

SCNNlA-4915 - CUCCCGCAGCCGUCGCGACCU 21 8764

SCNNlA-4916 - GCUCCCGCAGCCGUCGCGACCU 22 8765

SCNNlA-4917 - GGCUCCCGCAGCCGUCGCGACCU 23 8766

SCNNlA-4918 - CGGCUCCCGCAGCCGUCGCGACCU 24 8767

SCNNlA-4919 - GUCCUCUGGGGGGGCCCU 18 8768

SCNNlA-4920 - UGUCCUCUGGGGGGGCCCU 19 8769

SCNNlA-4921 - CUGUCCUCUGGGGGGGCCCU 20 8770

SCNNlA-4922 - CCUGUCCUCUGGGGGGGCCCU 21 8771

SCNNlA-4923 - ACCUGUCCUCUGGGGGGGCCCU 22 8772

SCNNlA-4924 - CACCUGUCCUCUGGGGGGGCCCU 23 8773

SCNNlA-4925 - CCACCUGUCCUCUGGGGGGGCCCU 24 8774

SCNNlA-4926 - AGUUCCUCCACCUGUCCU 18 8775

SCNNlA-4927 - CAGUUCCUCCACCUGUCCU 19 8776

SCNNlA-4928 - CCAGUUCCUCCACCUGUCCU 20 8777

SCNNlA-4929 - GCCAGUUCCUCCACCUGUCCU 21 8778

SCNNlA-4930 - GGCCAGUUCCUCCACCUGUCCU 22 8779

SCNNlA-4931 - GGGCCAGUUCCUCCACCUGUCCU 23 8780

SCNNlA-4932 - GGGGCCAGUUCCUCCACCUGUCCU 24 8781

SCNNlA-4933 - CAUGUUCCUCAUGCUGCU 18 8782

SCNNlA-4934 - UCAUGUUCCUCAUGCUGCU 19 8783

SCNNlA-4935 - AUCAUGUUCCUCAUGCUGCU 20 8784

SCNNlA-4936 - CAUCAUGUUCCUCAUGCUGCU 21 8785

SCNNlA-4937 - UCAUCAUGUUCCUCAUGCUGCU 22 8786

SCNNlA-4938 - GUCAUCAUGUUCCUCAUGCUGCU 23 8787

SCNNlA-4939 - GGUCAUCAUGUUCCUCAUGCUGCU 24 8788

SCNNlA-4940 - CGAGGGGGCAGGGGUGCU 18 8789

SCNNlA-4941 - CCGAGGGGGCAGGGGUGCU 19 8790

SCNNlA-4942 - GCCGAGGGGGCAGGGGUGCU 20 8791

SCNNlA-4943 - GGCCGAGGGGGCAGGGGUGCU 21 8792

SCNNlA-4944 - AGGCCGAGGGGGCAGGGGUGCU 22 8793

SCNNlA-4945 - CAGGCCGAGGGGGCAGGGGUGCU 23 8794

SCNNlA-4946 - CCAGGCCGAGGGGGCAGGGGUGCU 24 8795

SCNNlA-4947 - UUCCUCCACCUGUCCUCU 18 8796

SCNNlA-4948 - GUUCCUCCACCUGUCCUCU 19 8797

SCNNlA-1276 - AGUUCCUCCACCUGUCCUCU 20 5125

SCNNlA-4949 - CAGUUCCUCCACCUGUCCUCU 21 8798

1313

5535.1 SCNNlA-4950 - CCAGUUCCUCCACCUGUCCUCU 22 8799

SCNNlA-4951 - GCCAGUUCCUCCACCUGUCCUCU 23 8800

SCNNlA-4952 - GGCCAGUUCCUCCACCUGUCCUCU 24 8801

SCNNlA-4953 - UGACAUCCCAGGUAGAGU 18 8802

SCNNlA-4954 - GUGACAUCCCAGGUAGAGU 19 8803

SCNNlA-4955 - GGUGACAUCCCAGGUAGAGU 20 8804

SCNNlA-4956 - CGGUGACAUCCCAGGUAGAGU 21 8805

SCNNlA-4957 - UCGGUGACAUCCCAGGUAGAGU 22 8806

SCNNlA-4958 - CUCGGUGACAUCCCAGGUAGAGU 23 8807

SCNNlA-4959 - CCUCGGUGACAUCCCAGGUAGAGU 24 8808

SCNNlA-4960 - CCUGGAAUCAACAACGGU 18 8809

SCNNlA-4961 - GCCUGGAAUCAACAACGGU 19 8810

SCNNlA-4962 - UGCCUGGAAUCAACAACGGU 20 8811

SCNNlA-4963 - AUGCCUGGAAUCAACAACGGU 21 8812

SCNNlA-4964 - CAUGCCUGGAAUCAACAACGGU 22 8813

SCNNlA-4965 - CCAUGCCUGGAAUCAACAACGGU 23 8814

SCNNlA-4966 - UCCAUGCCUGGAAUCAACAACGGU 24 8815

SCNNlA-4967 - AUCAGGGGUGGAUGCGGU 18 8816

SCNNlA-4968 - CAUCAGGGGUGGAUGCGGU 19 8817

SCNNlA-4969 - UCAUCAGGGGUGGAUGCGGU 20 8818

SCNNlA-4970 - CUCAUCAGGGGUGGAUGCGGU 21 8819

SCNNlA-4971 - ACUCAUCAGGGGUGGAUGCGGU 22 8820

SCNNlA-4972 - UACUCAUCAGGGGUGGAUGCGGU 23 8821

SCNNlA-4973 - AUACUCAUCAGGGGUGGAUGCGGU 24 8822

SCNNlA-4974 - UGUGGGGAAGGGAUGGGU 18 8823

SCNNlA-4975 - GUGUGGGGAAGGGAUGGGU 19 8824

SCNNlA-1288 - AGUGUGGGGAAGGGAUGGGU 20 5137

SCNNlA-4976 - GAGUGUGGGGAAGGGAUGGGU 21 8825

SCNNlA-4977 - AGAGUGUGGGGAAGGGAUGGGU 22 8826

SCNNlA-4978 - UAGAGUGUGGGGAAGGGAUGGGU 23 8827

SCNNlA-4979 - GUAGAGUGUGGGGAAGGGAUGGGU 24

8828

SCNNlA-4980 - ACUUCCACCACCCGAUGU 18 8829

SCNNlA-4981 - CACUUCCACCACCCGAUGU 19 8830

SCNNlA-4982 - UCACUUCCACCACCCGAUGU 20 8831

SCNNlA-4983 - CUCACUUCCACCACCCGAUGU 21 8832

SCNNlA-4984 - UCUCACUUCCACCACCCGAUGU 22 8833

SCNNlA-4985 - CUCUCACUUCCACCACCCGAUGU 23 8834

SCNNlA-4986 - ACUCUCACUUCCACCACCCGAUGU 24 8835

SCNNlA-4987 - ACAU CCCAGG U AG AG UG U 18 8836

SCNNlA-4988 - GACAUCCCAGGUAGAGUGU 19 8837

SCNNlA-1293 - UGACAUCCCAGGUAGAGUGU 20 5142

1314

5535.1 SCNN lA-4989 - GUGACAUCCCAGGUAGAGUGU 21 8838

SCNN lA-4990 - GGUGACAUCCCAGGUAGAGUGU 22 8839

SCNN lA-4991 - CGGUGACAUCCCAGGUAGAGUGU 23 8840

SCNN lA-4992 - UCGGUGACAUCCCAGGUAGAGUGU 24 8841

SCNN lA-4993 - GAAACCCUGGACAGACUU 18 8842

SCNN lA-4994 - GGAAACCCUGGACAGACUU 19 8843

SCNN lA-1295 - AGGAAACCCUGGACAGACUU 20 5144

SCNN lA-4995 - UAGGAAACCCUGGACAGACUU 21 8844

SCNN lA-4996 - AUAGGAAACCCUGGACAGACUU 22 8845

SCNN lA-4997 - CAUAGGAAACCCUGGACAGACUU 23 8846

SCNN lA-4998 - UCAUAGGAAACCCUGGACAGACUU 24 8847

SCNN lA-4999 - UAGCGUGGCCUCCAGCUU 18 8848

SCNN lA-5000 - GUAGCGUGGCCUCCAGCUU 19 8849

SCNN lA-5001 - CGUAGCGUGGCCUCCAGCUU 20 8850

SCNN lA-5002 - CCGUAGCGUGGCCUCCAGCUU 21 8851

SCNN lA-5003 - CCCGUAGCGUGGCCUCCAGCUU 22 8852

SCNN lA-5004 - GCCCGUAGCGUGGCCUCCAGCUU 23 8853

SCNN lA-5005 - AGCCCGUAGCGUGGCCUCCAGCUU 24 8854

SCNN lA-5006 - CAUGCUGCUCCGAAGGUU 18 8855

SCNN lA-5007 - UCAUGCUGCUCCGAAGGUU 19 8856

SCNN lA-5008 - CUCAUGCUGCUCCGAAGGUU 20 8857

SCNN lA-5009 - CCUCAUGCUGCUCCGAAGGUU 21 8858

SCNN lA-5010 - UCCUCAUGCUGCUCCGAAGGUU 22 8859

SCNN lA-5011 - UUCCUCAUGCUGCUCCGAAGGUU 23 8860

SCNN lA-5012 - GUUCCUCAUGCUGCUCCGAAGGUU 24 8861

SCNN lA-5013 - GGCAGUGAUGUUCCUGUU 18 8862

SCNN lA-5014 - UGGCAGUGAUGUUCCUGUU 19 8863

SCNN lA-5015 - AUGGCAGUGAUGUUCCUGUU 20 8864

SCNN lA-5016 - AAUGGCAGUGAUGUUCCUGUU 21 8865

SCNN lA-5017 - GAAUGGCAGUGAUGUUCCUGUU 22 8866

SCNN lA-5018 - AGAAUGGCAGUGAUGUUCCUGUU 23 8867

SCNN lA-5019 - AAGAAUGGCAGUGAUGUUCCUGU U 24 8868

Table 45A provides exemplary targeting domains for knocking out the SCNN1A gene selected according to the first tier parameters. The targeting domains bind within the first 500 bp of the coding sequence (e.g., with 500 bp downstream from the start codon), have a high level of orthogonality and start with a 5'G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

1315

5535.1 Table 45A

Table 45B provides exemplary targeting domains for knocking out the SCNN1A gene selected according to the second tier parameters. The targeting domains bind within the first 500 bp of the coding sequence (e.g., with 500 bp downstream from the start codon) and have a high level of orthogonality. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 45B

Table 45C provides exemplary targeting domains for knocking out the SCNN1A gene selected according to the third tier parameters. The targeting domains bind within the first 500 bp of the coding sequence (e.g., with 500 bp downstream from the start codon) and start with a 5'G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 45C

1316

5535.1 3rd Tier

Target Site

gRNA Name DNA Strand Targeting Domain

Length Seq ID

SCNNlA-5028 + GGCCCAGCCCCUGCUCC 17 8877

SCNNlA-5029 + GAGGGCUAGAGUCCUGCUCC 20 8878

SCNNlA-5030 + GAGGUCUAGGGUCCUGCUCC 20 8879

Table 45D provides exemplary targeting domains for knocking out the SCNN1A gene selected according to the fourth tier parameters. The targeting domains bind within the first 500 bp of the coding sequence (e.g., with 500 bp downstream from the start codon). It is

contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 45D

Table 45E provides exemplary targeting domains for knocking out the SCNN1A gene selected according to the fifth tier parameters. The targeting domains fall in the coding sequence of the gene, downstream of the first 500bp of coding sequence (e.g., anywhere from +500 (relative to the start codon) to the stop codon of the gene). It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 45E

1317

5535.1 SCNNlA-485 + GCGCCAUGGAGCAAGCA 17 4334

SCNNlA-5035 + UAUGUCUGGUAGAAGCA 17 8884

SCNNlA-5036 - UCCAGGUGUGUAUUCAC 17 8885

SCNNlA-577 + CUGAGGAGAAGUCAACC 17 4426

SCNNlA-5037 - GCUUGCUCCAUGGCGCC 17 8886

SCNNlA-5038 - GCAACUUCAUCUUCGCC 17 8887

SCNNlA-5039 - GAGCCCGUAGCGUGGCC 17 8888

SCNNlA-5040 - ACUGGAAGGACUGGAAG 17 8889

SCNNlA-5041 - GCAACCAGAACAAAUCG 17 8890

SCNNlA-5042 - AUGCGGUGAGGGAGUGG 17 8891

SCNNlA-787 - ACCCUGGACAGACUUGG 17 4636

SCNNlA-5043 + AAGGGGACACUAACCUG 17 8892

SCNNlA-5044 - CUGCCUUUAUGGAUGAU 17 8893

SCNNlA-5045 - AACAACGGUGAGAAGCU 17 8894

SCNNlA-5046 + UCGGCCUGGAGACCAGU 17 8895

SCNNlA-5047 + AGGGAGCUUCUCACCGU 17 8896

SCNNlA-5048 + CUGGAGUCUCACCCCAGGAA 20 8897

SCNNlA-5049 - CACACAGCAGGUGAGGCCCA 20 8898

SCNNlA-909 + AGGGCGCCAUGGAGCAAGCA 20 4758

SCNNlA-5050 + GAGUAUGUCUGGUAGAAGCA 20 8899

SCNNlA-5051 - CCUUCCAGGUGUGUAUUCAC 20 8900

SCNNlA-1000 + GGUCUGAGGAGAAGUCAACC 20 4849

SCNNlA-5052 - CCUGCUUGCUCCAUGGCGCC 20 8901

SCNNlA-5053 - UGGGCAACUUCAUCUUCGCC 20 8902

SCNNlA-5054 - GUCGAGCCCGUAGCGUGGCC 20 8903

SCNNlA-5055 - UGGACUGGAAGGACUGGAAG 20 8904

SCNNlA-5056 - AGUGCAACCAGAACAAAUCG 20 8905

SCNNlA-5057 - UGGAUGCGGUGAGGGAGUGG 20 8906

SCNNlA-1206 - G AAACCCUGGACAGACU UGG 20 5055

SCNNlA-5058 + GGGAAGGGGACACUAACCUG 20 8907

SCNNlA-5059 - AACCUGCCUUUAUGGAUGAU 20 8908

SCNNlA-5060 - AUCAACAACGGUGAGAAGCU 20 8909

SCNNlA-5061 + CCCUCGGCCUGGAGACCAGU 20 8910

SCNNlA-5062 + AGCAGGGAGCUUCUCACCGU 20 8911

Table 46A provides exemplary targeting domains for knocking down the SCNN1A gene selected according to the first tier parameters. The targeting domains bind within 500 bp (e.g., upstream or downstream) of a transcription start site (TSS), have a high level of orthogonality and start with a 5'G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting

1318

5535.1 domains in the table can be used with a S. pyogenes eiCas9 molecule or eiCas9 fusion protein (e.g., an eiCas9 fused to a transcription repressor domain) to alter the SCNNIA gene (e.g., reduce or eliminate SCNNIA gene expression, SCNNIA protein function, or the level of SCNNIA protein). One or more gRNA may be used to target an eiCas9 to the promoter region the SCNNIA gene.

Table 46A

1319

5535.1 SCNNlA-5089 - GAGGAGAGGCCGUUCUA 17 8938

SCNNlA-5090 - GGAGACUGGAGUUUCUA 17 8939

SCNNlA-5091 - GGACCAUGCCCAAUGUA 17 8940

SCNNlA-5092 - GGAAUCCUGGUUGACAC 17 8941

SCNNlA-5093 + GGCUGCCGCUUCCUCAC 17 8942

SCNNlA-5094 + GGGCUUUAGACGCAGAC 17 8943

SCNNlA-5095 + GAAAGCCGGUGUCAACC 17 8944

SCNNlA-5096 + GAGCAUUGAUACACACC 17 8945

SCNNlA-5097 + GAUUCUGUCUCUGCCCC 17 8946

SCNNlA-5098 - GGGCGGGCUCCCCAGCC 17 8947

SCNNlA-5099 - GCUGAGCCUCUAGCUCC 17 8948

SCNNlA-5100 - GGGCGAUUACACAUUCC 17 8949

SCNNlA-5101 + GUCCCAAGUGUGCUUCC 17 8950

SCNNlA-5102 - GGUGGCGAGGAAUCAGC 17 8951

SCNNlA-5103 + G C C A A A AG UGCCGGAGC 17 8952

SCNNlA-5104 + GAGGAUGUGGCCAGCGC 17 8953

SCNNlA-5105 + GAAGCUGGGGGCUAGGC 17 8954

SCNNlA-5106 + GAAGGCGGACUCUGGGC 17 8955

SCNNlA-5107 + GGAGCCCGCCCGCUGGC 17 8956

SCNNlA-5108 + GCCUAGGGGCUCACUGC 17 8957

SCNNlA-5109 + GGAGCCAGCAGACCUGC 17 8958

SCNNlA-5110 - GCUGGGCCUUUGUCUGC 17 8959

SCNNlA-5111 + GUUGGGGCCAAAAGUGC 17 8960

SCNNlA-5112 + GCAGGCACUGAAGGUGC 17 8961

SCNNlA-5113 + GUCUGCUCUCUGGGUGC 17 8962

SCNNlA-5114 - GCUGAGCACCUUAUUGC 17 8963

SCNNlA-5115 - GGGGCAGAGACAGAAUC 17 8964

SCNNlA-5116 + GUGGGAGCAGCGCACUC 17 8965

SCNNlA-333 - GAUGGGAGAGGGCACUC 17 4182

SCNNlA-5117 - GGCCCUCGCGCUGCCUC 17 8966

SCNNlA-5118 + GGCAGUACUCCAGGCUC 17 8967

SCNNlA-5119 - GGUGUGUAUCAAUGCUC 17 8968

SCNNlA-5120 - GAGUUUCUAGGGGUCUC 17 8969

SCNNlA-5121 - GGACACAGCUCGAGGUC 17 8970

SCNNlA-5122 - GCUAGUGGUUGGAUUUC 17 8971

SCNNlA-5123 + GCUAGAGGCUCAGCAAG 17 8972

SCNNlA-5124 + GGAAUGUGGGCAACCAG 17 8973

SCNNlA-334 - GACAUGGGCAUGGCCAG 17 4183

SCNNlA-5125 + GGGCUAGGGGAGCCUAG 17 8974

SCNNlA-5126 + GUGCUUCCAGGAGCUAG 17 8975

SCNNlA-5127 - GAGACUGGAGUUUCUAG 17 8976

SCNNlA-5128 + GGGCACUGAGUGAGUAG 17 8977

1320

5535.1 SCNNlA-5129 - GUCCACAGUGUCCUGCG 17 8978

SCNNlA-5130 - GGACAAAACUCGAAAGG 17 8979

SCNNlA-5131 + GACGCAGACAGGCAAGG 17 8980

SCNNlA-5132 + GGAACCGGGAGGACAGG 17 8981

SCNNlA-5133 + GGAGCAGCGCACUCAGG 17 8982

SCNNlA-5134 - GUAGAUAGCCCCAGAGG 17 8983

SCNNlA-5135 - GGGCCUAGAGUGAGAGG 17 8984

SCNNlA-5136 + GCAUUGAUACACACCGG 17 8985

SCNNlA-5137 + GCACUGAAGGUGCAGGG 17 8986

SCNNlA-5138 + GACCCAAAAAGGGCUGG 17 8987

SCNNlA-5139 - GGUCUGGACAAGGUUGG 17 8988

SCNNlA-5140 - GGGGUCUCUGGGAUAUG 17 8989

SCNNlA-5141 + GGCCACGCAGGACACUG 17 8990

SCNNlA-5142 + GUGCAGCGGCCUGGCUG 17 8991

SCNNlA-5143 + GGGUCCAACCUGGUCUG 17 8992

SCNNlA-5144 + GAUAAAUCAGUUUUCUG 17 8993

SCNNlA-5145 + GUGAGUAGAGGCAGGUG 17 8994

SCNNlA-5146 - GCUGCACCUGUCAGGUG 17 8995

SCNNlA-5147 - GGUCUCUGGGAUAUGUG 17 8996

SCNNlA-335 - GGCGCAGGGUGGGACAU 17 4184

SCNNlA-5148 + GAGCCAGGUCCUUACAU 17 8997

SCNNlA-5149 + GCGAAGGACAGAGAGAU 17 8998

SCNNlA-5150 + GGGCUAGGCGGGGCCCU 17 8999

SCNNlA-5151 - GAAAACUGAUUUAUCCU 17 9000

SCNNlA-5152 + GUGCUGGGUUAUCUCCU 17 9001

SCNNlA-5153 - GUAUCAAUGCUCAGGCU 17 9002

SCNNlA-5154 + GGUGCAGCGGCCUGGCU 17 9003

SCNNlA-336 + GGUCAAGGCUGAGCUCU 17 4185

SCNNlA-5155 + GGAUUCGUCUGCUCUCU 17 9004

SCNNlA-5156 - GAGAUGACACCUUCUCU 17 9005

SCNNlA-5157 - GGGAGACUGGAGUUUCU 17 9006

SCNNlA-5158 - GGGAUAUGUGGGGCAGU 17 9007

SCNNlA-5159 + GAGCAGCGCACUCAGGU 17 9008

SCNNlA-337 - GAAUGUGGGCGCAGGGU 17 4186

SCNNlA-5160 - GGGUCUCUGGGAUAUGU 17 9009

SCNNlA-5161 + GUUCUUUUUUACACUGU 17 9010

SCNNlA-5162 - GGGUGAGGCUGACCUGU 17 9011

SCNNlA-5163 - GUUGCCCUCCUAGCUGU 17 9012

SCNNlA-5164 - GGGUCAGUUUCUUCAUU 17 9013

SCNNlA-339 + GAGCCCCGGAGUGGAUU 17 4188

SCNNlA-5165 - GGGAGCCCUCCUUCCUU 17 9014

SCNNlA-5166 + GCAGACCUGCGGGAGUU 17 9015

1321

5535.1 SCNNlA-5167 + GCAAGUGGGCAGCCCUCCAA 20 9016

SCNNlA-5168 + GUCUCCAGGAAGGAGAGCAA 20 9017

SCNNlA-5169 + GCAAAUAGUUUUCAUAUCAA 20 9018

SCNNlA-5170 + GGAGGGCAACACAAGGAGAA 20 9019

SCNNlA-5171 + GGAGCUGGGCUUCCCUAGAA 20 9020

SCNNlA-5172 - GUGCUAGGACAAAACUCGAA 20 9021

SCNNlA-5173 - GCUGCCAGAUUCAACUGGAA 20 9022

SCNNlA-5174 + GGAUGUGGCCAGCGCUGGAA 20 9023

SCNNlA-5175 - GCCCCUCCCGGGUCUGGACA 20 9024

SCNNlA-5176 + GAAGAAACUGACCCUUCCCA 20 9025

SCNNlA-5177 + GAGAUAAGACAUAAGAGCCA 20 9026

SCNNlA-5178 + GCCCGCCCGCUGGCCGGCCA 20 9027

SCNNlA-340 - GUGGGACAUGGGCAUGGCCA 20 4189

SCNNlA-341 - GCAGCCUCACUCGGGUUCCA 20 4190

SCNNlA-342 - GAGCAGUAUCAAGGUAAGCA 20 4191

SCNNlA-5179 + GGAGUGCCAAGUGGUGAGCA 20 9028

SCNNlA-5180 - G C U G G C A A A U AG A A A AG G C A 20 9029

SCNNlA-5181 + GCUUUAGACGCAGACAGGCA 20 9030

SCNNlA-5182 - GCCUAGAGUGAGAGGGGGCA 20 9031

SCNNlA-5183 + GAGAAGGCGGACUCUGGGCA 20 9032

SCNNlA-5184 - GUGCUGAGCACCUUAUUGCA 20 9033

SCNNlA-5185 + GGCAAAUAGUUUUCAUAUCA 20 9034

SCNNlA-343 - GUGAUGGGAGAGGGCACUCA 20 4192

SCNNlA-5186 + GGAAGGCUGCCGCUUCCUCA 20 9035

SCNNlA-1 - GCAGCCCAUACCAGGUCUCA 20 503

SCNNlA-5187 + GCCAGCGCUGGAAAGGAAGA 20 9036

SCNNlA-5188 - GCUGAGGGCCUAGAGUGAGA 20 9037

SCNNlA-5189 + GGCAACCAGAGGCAGCGCGA 20 9038

SCNNlA-5190 + GCCGGGAGUUUUCCGAAGGA 20 9039

SCNNlA-5191 + GGAGUUUUCCGAAGGAAGGA 20 9040

SCNNlA-5192 + GCCCGCUGGCCGGCCAGGGA 20 9041

SCNNlA-5193 + GGCCCUGCACGCGGCAGGGA 20 9042

SCNNlA-76 + GCCCUGGAGUGGACUGUGGA 20 528

SCNNlA-5194 - GACCUGUGGGUGCCCUUGGA 20 9043

SCNNlA-5195 + GAGGAGGAGAAAUUCGUUGA 20 9044

SCNNlA-5196 + GCAUGGUCCUCCCUGCAAUA 20 9045

SCNNlA-5197 + GCCUGCAAUACAAUAAGAUA 20 9046

SCNNlA-5198 + GACAUAAGAGCCAAGGGCUA 20 9047

SCNNlA-344 + GUAUGGGCUGCAGAGGUCUA 20 4193

SCNNlA-5199 - GCAGAGGAGAGGCCGUUCUA 20 9048

SCNNlA-5200 - GGAGGACCAUGCCCAAUGUA 20 9049

SCNNlA-5201 + GAAAUCCAACCACUAGCUUA 20 9050

1322

5535.1 SCNNlA-5202 - GUUUGGCUGCCAGAUUCAAC 20 9051

SCNNlA-5203 + GCUCCCGAGGGCAGGUGAAC 20 9052

SCNNlA-5204 + GCCUGAGCAUUGAUACACAC 20 9053

SCNNlA-5205 + GAAGGCUGCCGCUUCCUCAC 20 9054

SCNNlA-5206 + GAGUGCAGGAAUGUGGUCAC 20 9055

SCNNlA-5207 - GGACCUGGCUCAAGGGAGAC 20 9056

SCNNlA-5208 + GGCAUGGCACACGCCUAGAC 20 9057

SCNNlA-5209 + GGGUGGGGAACCGGGAGGAC 20 9058

SCNNlA-5210 + GGUUGCGGCUGGACUGGGAC 20 9059

SCNNlA-5211 + GGCAGGUGAACUGGGAGUAC 20 9060

SCNNlA-5212 + G U CAACCAGG AU U CCAAACC 20 9061

SCNNlA-5213 - GUCCCAGUCCAGCCGCAACC 20 9062

SCNNlA-5214 + GAGGGCCUGGGUGGGGAACC 20 9063

SCNNlA-5215 + GAUCGGGGCUCAGGUGCACC 20 9064

SCNNlA-5216 - GCCUAGCCCCCAGCUUCACC 20 9065

SCNNlA-5217 + GGACACUGUGGACACAGACC 20 9066

SCNNlA-5218 - GUCCUCCCGGUUCCCCACCC 20 9067

SCNNlA-346 + GUGCCCUCUCCCAUCACCCC 20 4195

SCNNlA-5219 + GCACACGCCUAGACAGGCCC 20 9068

SCNNlA-5220 - GCUUCACCUGGGCCCCUCCC 20 9069

SCNNlA-5221 + GCUGAGGAGGAGUCAGAGCC 20 9070

SCNNlA-347 - GGUGGGACAUGGGCAUGGCC 20 4196

SCNNlA-5222 - GCGAUUACACAUUCCUGGCC 20 9071

SCNNlA-5223 + GUGAGAAGAAUUGCAAUGCC 20 9072

SCNNlA-5224 - GGGAACCUGGUUUGGAAUCC 20 9073

SCNNlA-5225 + GGGAUGCGUCUGCCUCCUCC 20 9074

SCNNlA-5226 + GGAGUCCCAAGUGUGCUUCC 20 9075

SCNNlA-348 - GGCAGCCUCACUCGGGUUCC 20 4197

SCNNlA-5227 + GUGCACCUGGAUGUGAAAGC 20 9076

SCNNlA-176 - GCUCAUGAAGGGGAACAAGC 20 811

SCNNlA-5228 - GCAACCUGGGAGUGGGAAGC 20 9077

SCNNlA-5229 - GGGGGUGGCGAGGAAUCAGC 20 9078

SCNNlA-5230 - GCUGCUCCCACUUAGUGAGC 20 9079

SCNNlA-349 - GAGUGGGAGAAUGUGGGCGC 20 4198

SCNNlA-5231 - GUGUGUAUCAAUGCUCAGGC 20 9080

SCNNlA-5232 + GAAUCAGACCCAAAAAGGGC 20 9081

SCNNlA-5233 + GAAGGAGGGCUCCCGAGGGC 20 9082

SCNNlA-5234 + GACAGGUGCAGCGGCCUGGC 20 9083

SCNNlA-5235 + GGAGCCUAGGGGCUCACUGC 20 9084

SCNNlA-5236 + GGAGUUGGGGCCAAAAGUGC 20 9085

SCNNlA-5237 - GGUGCUGAGCACCUUAUUGC 20 9086

SCNNlA-5238 + GGUUCCUUUCCAGUUGAAUC 20 9087

1323

5535.1 SCNNlA-350 - GGUGAUGGGAGAGGGCACUC 20 4199

SCNNlA-351 - GGCCAGGGGCAGCCUCACUC 20 4200

SCNNlA-5239 + GGGCUCACUGCAGGAGACUC 20 9088

SCNNlA-5240 + GGACCUGAGAAGGCGGACUC 20 9089

SCNNlA-5241 - GUUCUAGGGAAGCCCAGCUC 20 9090

SCNNlA-5242 - GCCCUCCUAGCUGUGGGCUC 20 9091

SCNNlA-352 + GAUUGGGGAGAGCAAGGGUC 20 4201

SCNNlA-5243 - GCCAGGCCGCUGCACCUGUC 20 9092

SCNNlA-5244 - GCGAGGAAUCAGCAGGAAAG 20 9093

SCNNlA-5245 + GGAGCUAGAGGCUCAGCAAG 20 9094

SCNNlA-5246 - GUGAGAGGGGGCAAGGCAAG 20 9095

SCNNlA-5247 + GGCCAGCGCUGGAAAGGAAG 20 9096

SCNNlA-5248 + GCAGGAAUGUGGGCAACCAG 20 9097

SCNNlA-5249 - GCAAGAGACUGCCGCAAGAG 20 9098

SCNNlA-5250 - GAAACAGAAGGCAGAUAGAG 20 9099

SCNNlA-5251 - GUCCAGCCGCAACCUGGGAG 20 9100

SCNNlA-5252 - GGGUCUGGACAAGGUUGGAG 20 9101

SCNNlA-5253 - GCCAUGCUGCCUUAAGCUAG 20 9102

SCNNlA-5254 + GAGGGGCACUGAGUGAGUAG 20 9103

SCNNlA-353 - GCUCUCCCCAAUCCACUCCG 20 4202

SCNNlA-5255 + GGGCAACCAGAGGCAGCGCG 20 9104

SCNNlA-5256 + GUGAAGCUGGGGGCUAGGCG 20 9105

SCNNlA-5257 + GACAGACUCAUGGGGGAUCG 20 9106

SCNNlA-5258 + GAGUACUGGACCUGAGAAGG 20 9107

SCNNlA-5259 + GGGAGUUUUCCGAAGGAAGG 20 9108

SCNNlA-5260 + GUGGGAGCAGCGCACUCAGG 20 9109

SCNNlA-5261 - GUAGAUAGCCCCAGAGGAGG 20 9110

SCNNlA-5262 - GGUCUGGACAAGGUUGGAGG 20 9111

SCNNlA-354 - GGGAGAAUGUGGGCGCAGGG 20 4203

SCNNlA-5263 - G G C A A A U AG A A A AG G C AG G G 20 9112

SCNNlA-5264 + GGCCUGGGUGGGGAACCGGG 20 9113

SCNNlA-5265 + GCAUUGAUACACACCGGGGG 20 9114

SCNNlA-2 - GCCCAUACCAGGUCUCAUGG 20 497

SCNNlA-5266 - GCUGGCUCCAGGAAAGGUGG 20 9115

SCNNlA-5267 + GUCACAGAGUUGCAGGAAUG 20 9116

SCNNlA-5268 + GAGGGCCACGCAGGACACUG 20 9117

SCNNlA-5269 - GCACUCUGGGCUGCCUCCUG 20 9118

SCNNlA-5270 - GCCGCUGCACCUGUCAGGUG 20 9119

SCNNlA-5271 - GGCCUUUGUCUGCUGGCUUG 20 9120

SCNNlA-355 - GUGGGCGCAGGGUGGGACAU 20 4204

SCNNlA-5272 + GAGACAGACUCAUGGGGGAU 20 9121

SCNNlA-5273 - GUCUCCUGCAGUGAGCCCCU 20 9122

1324

5535.1 SCNNlA-5274 - GGCUGACCUGUGGGUGCCCU 20 9123

SCNNlA-5275 + GCCAAGGGCUAGGGGAGCCU 20 9124

SCNNlA-5276 + GCCUUGCCCCCUCUCACUCU 20 9125

SCNNlA-5277 + GACCUGAGAAGGCGGACUCU 20 9126

SCNNlA-356 + GGUAUGGGCUGCAGAGGUCU 20 4205

SCNNlA-5278 + GCCAGCAGACCUGCGGGAGU 20 9127

SCNNlA-5279 - GAGGAAGCCACAGACCAGGU 20 9128

SCNNlA-357 - GGAGAAUGUGGGCGCAGGGU 20 4206

SCNNlA-5280 + GCGCUGGAAAGGAAGAGGGU 20 9129

SCNNlA-5281 - GUGCAGGGCCUGGGUUGUGU 20 9130

SCNNlA-5282 - GAAGGGUCAGUUUCUUCAUU 20 9131

SCNNlA-5283 - GAGUCUCCUCCAGCCCUUUU 20 9132

Table 46B provides exemplary targeting domains for knocking down the SCNNIA gene selected according to the second tier parameters. The targeting domains bind within 500 bp (e.g., upstream or downstream) of a transcription start site (TSS) and have a high level of

orthogonality. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. pyogenes eiCas9 molecule or eiCas9 fusion protein (e.g., an eiCas9 fused to a transcription repressor domain) to alter the SCNNIA gene (e.g., reduce or eliminate SCNNIA gene expression, SCNNIA protein function, or the level of SCNNIA protein). One or more gRNA may be used to target an eiCas9 to the promoter region of the SCNNIA gene.

Table 46B

1325

5535.1 SCNNlA-360 - ACUCCGGGGCUCAUGAA 17 4209

SCNNlA-5294 + AUUAGCAUCUCAAUUAA 17 9143

SCNNlA-5295 - CCUCCCGGGUCUGGACA 17 9144

SCNNlA-5296 - UUGAGAUCAAACAGCCA 17 9145

SCNNlA-5297 + AUAAGACAUAAGAGCCA 17 9146

SCNNlA-5298 - ACCUUUUCACAGAGCCA 17 9147

SCNNlA-5299 + CGCCCGCUGGCCGGCCA 17 9148

SCNNlA-88 - CUCCACAGUCCACUCCA 17 609

SCNNlA-5300 + AAGUGGGCAGCCCUCCA 17 9149

SCNNlA-5301 + C U G AAU C U U G AC AAG CA 17 9150

SCNNlA-361 - CAGUAUCAAGGUAAGCA 17 4210

SCNNlA-5302 - ACUCUGUGACCACAGCA 17 9151

SCNNlA-5303 + ACUAGCUUAAGGCAGCA 17 9152

SCNNlA-5304 + U C A A U U A A AG G U G AG C A 17 9153

SCNNlA-5305 - UGAGAGGGGGCAAGGCA 17 9154

SCNNlA-5306 + UUAGACGCAGACAGGCA 17 9155

SCNNlA-5307 + AGGCCCUGCACGCGGCA 17 9156

SCNNlA-5308 - CUUCCCUGCCGCGUGCA 17 9157

SCNNlA-5309 + C AGG CAC U G AAG G U G C A 17 9158

SCNNlA-5310 - CUGAGCACCUUAUUGCA 17 9159

SCNNlA-362 - UAUCAUGAGCAGUAUCA 17 4211

SCNNlA-363 - AUGGGAGAGGGCACUCA 17 4212

SCNNlA-5311 + UUCCUGAGACAGACUCA 17 9160

SCNNlA-5312 + AGGCUGCCGCUUCCUCA 17 9161

SCNNlA-5313 - UGUAAGGACCUGGCUCA 17 9162

SCNNlA-5314 + AGCGCUGGAAAGGAAGA 17 9163

SCNNlA-5315 + AGGGCAACACAAGGAGA 17 9164

SCNNlA-5316 + UGGUGGGGGCAAAUAGA 17 9165

SCNNlA-5317 + AGCCGGGAGUUUUCCGA 17 9166

SCNNlA-5318 + AACCAGAGGCAGCGCGA 17 9167

SCNNlA-5319 + UGAGCCCACAGCUAGGA 17 9168

SCNNlA-5320 + CGCUGGCCGGCCAGGGA 17 9169

SCNNlA-5321 + CCUGCACGCGGCAGGGA 17 9170

SCNNlA-5322 + CUUGUCCAGACCCGGGA 17 9171

SCNNlA-5323 + UGAGCAGGGCGGGGGGA 17 9172

SCNNlA-5324 - UGACACCUUCUCUGGGA 17 9173

SCNNlA-82 - AUACCAGGUCUCAUGGA 17 501

SCNNlA-364 + UGAUACCUCCCCUUGGA 17 4213

SCNNlA-5325 - CUGUGGGUGCCCUUGGA 17 9174

SCNNlA-365 - CACUCCGGGGCUCAUGA 17 4214

SCNNlA-5326 - CUGCACCUGUCAGGUGA 17 9175

SCNNlA-366 - UCGGGUUCCAGGGGUGA 17 4215

1326

5535.1 SCNNlA-5327 + UGGUCCUCCCUGCAAUA 17 9176

SCNNlA-5328 + CGAAGGACAGAGAGAUA 17 9177

SCNNlA-5329 + AGGGCUAGGGGAGCCUA 17 9178

SCNNlA-5330 - AAGAACAGAAUGUCCUA 17 9179

SCNNlA-5331 + AUAAGAGCCAAGGGCUA 17 9180

SCNNlA-157 + CUCCAUGAGACCUGGUA 17 502

SCNNlA-5332 + AUCCAACCACUAGCUUA 17 9181

SCNNlA-5333 - UGGCUGCCAGAUUCAAC 17 9182

SCNNlA-5334 + CCCGAGGGCAGGUGAAC 17 9183

SCNNlA-5335 + UGAGCAUUGAUACACAC 17 9184

SCNNlA-5336 + CCUCCAAGGGCACCCAC 17 9185

SCNNlA-5337 + UUCCUCACGGGCCCCAC 17 9186

SCNNlA-5338 - AGAGCAGACGAAUCCAC 17 9187

SCNNlA-5339 + UGCAGGAAUGUGGUCAC 17 9188

SCNNlA-5340 - CCUGGCUCAAGGGAGAC 17 9189

SCNNlA-5341 + AUGGCACACGCCUAGAC 17 9190

SCNNlA-5342 + CCAGGGAUGGAAGCGAC 17 9191

SCNNlA-5343 + UGGGGAACCGGGAGGAC 17 9192

SCNNlA-5344 + UGCGGCUGGACUGGGAC 17 9193

SCNNlA-5345 + CCAGGUUGCGGCUGGAC 17 9194

SCNNlA-5346 + CCUCCCCCUCACCUGAC 17 9195

SCNNlA-5347 + AGGUGAACUGGGAGUAC 17 9196

SCNNlA-5348 + AGGCUCAGGGUCCAACC 17 9197

SCNNlA-5349 - CCAGUCCAGCCGCAACC 17 9198

SCNNlA-5350 + CCAACCUUGUCCAGACC 17 9199

SCNNlA-156 + UUCCCCUCCAUGAGACC 17 653

SCNNlA-5351 - UGCCCAAUGUAAGGACC 17 9200

SCNNlA-368 - CCUCUGCAGCCCAUACC 17 4217

SCNNlA-5352 - CUCCCGGUUCCCCACCC 17 9201

SCNNlA-5353 + UAAGGUGCUCAGCACCC 17 9202

SCNNlA-5354 + CAACCUUGUCCAGACCC 17 9203

SCNNlA-369 + CCGAGUGAGGCUGCCCC 17 4218

SCNNlA-5355 - AGGCCUAUCUCCUCCCC 17 9204

SCNNlA-5356 + ACACAGACCCGGAGCCC 17 9205

SCNNlA-5357 + AGACCCGGGAGGGGCCC 17 9206

SCNNlA-5358 - CCUGUCGCUUCCAUCCC 17 9207

SCNNlA-5359 - AGGUUGGACCCUGAGCC 17 9208

SCNNlA-5360 + CCAGUCUCCCUUGAGCC 17 9209

SCNNlA-5361 + CCGCCCGCUGGCCGGCC 17 9210

SCNNlA-5362 + UGACAGGUGCAGCGGCC 17 9211

SCNNlA-5363 - CUGCCGCGUGCAGGGCC 17 9212

SCNNlA-5364 + AGAAGAAUUGCAAUGCC 17 9213

1327

5535.1 SCNNlA-5365 + UUACACUGUUGGCUGCC 17 9214

SCNNlA-5366 - UCCCGGCUUUCACAUCC 17 9215

SCNNlA-5367 - AGCUGAGACACAGAUCC 17 9216

SCNNlA-5368 - UUCCUUCGGAAAACUCC 17 9217

SCNNlA-370 - UCUCCCCAAUCCACUCC 17 4219

SCNNlA-87 - CCUCCACAGUCCACUCC 17 608

SCNNlA-5369 + AG AAAAG G C AG U AC U CC 17 9218

SCNNlA-5370 - UUCACCUGGGCCCCUCC 17 9219

SCNNlA-5371 + AUGCGUCUGCCUCCUCC 17 9220

SCNNlA-5372 + UUUGGUCUUCUUCCUCC 17 9221

SCNNlA-5373 + AAAGGGAGUCUGUCUCC 17 9222

SCNNlA-371 - AGCCUCACUCGGGUUCC 17 4220

SCNNlA-5374 + CUUCUUAAAGUGAAAGC 17 9223

SCNNlA-5375 + CACCUGGAUGUGAAAGC 17 9224

SCNNlA-260 - C A U G A AG G G G A AC A AG C 17 868

SCNNlA-84 - CAUGGAGGGGAACAAGC 17 607

SCNNlA-5376 + AGGGGCCCAGGUGAAGC 17 9225

SCNNlA-5377 - AACUCUGUGACCACAGC 17 9226

SCNNlA-372 + CCCUUGGAAGGGACAGC 17 4221

SCNNlA-5378 - AUCCCUGGCCGGCCAGC 17 9227

SCNNlA-5379 + CUCAAUUAAAGGUGAGC 17 9228

SCNNlA-5380 + C A AG C A AG G AG U U U AG C 17 9229

SCNNlA-5381 + CAGCGCGAGGGCCACGC 17 9230

SCNNlA-5382 + CUGGGGAGCCCGCCCGC 17 9231

SCNNlA-5383 - UUGGCCCCAACUCCCGC 17 9232

SCNNlA-5384 - CUCUUCCUUUCCAGCGC 17 9233

SCNNlA-373 - UGGGAGAAUGUGGGCGC 17 4222

SCNNlA-5385 - U G G C A A A U AG A A A AG G C 17 9234

SCNNlA-5386 - UGUAUCAAUGCUCAGGC 17 9235

SCNNlA-5387 + ACUGAGUGAGUAGAGGC 17 9236

SCNNlA-5388 + CAGGCCCUGCACGCGGC 17 9237

SCNNlA-5389 + CACUCCCAGGUUGCGGC 17 9238

SCNNlA-5390 + UCAGACCCAAAAAGGGC 17 9239

SCNNlA-5391 + UUAAAGGUGAGCAGGGC 17 9240

SCNNlA-5392 - CUGGCCGGCCAGCGGGC 17 9241

SCNNlA-5393 - UCGCUUCCAUCCCUGGC 17 9242

SCNNlA-5394 + AGGUGCAGCGGCCUGGC 17 9243

SCNNlA-5395 + AGAGAAGAGGUCUCUGC 17 9244

SCNNlA-5396 - AACUCCCGCAGGUCUGC 17 9245

SCNNlA-5397 - CCUUCCCUGCCGCGUGC 17 9246

SCNNlA-5398 - CAGACUCCCUUUGGUGC 17 9247

SCNNlA-5399 - UUAUCUUAUUGUAUUGC 17 9248

1328

5535.1 SCNNlA-5400 + UGUGGUCACAGAGUUGC 17 9249

SCNNlA-5401 + UCCUUUCCAGUUGAAUC 17 9250

SCNNlA-5402 + CAGACUCAUGGGGGAUC 17 9251

SCNNlA-5403 - CGAAAGGUGGCCCUAUC 17 9252

SCNNlA-374 - CUCUCCCCAAUCCACUC 17 4223

SCNNlA-375 - CAGGGGCAGCCUCACUC 17 4224

SCNNlA-5404 + CUCACUGCAGGAGACUC 17 9253

SCNNlA-5405 + CCUGAGAAGGCGGACUC 17 9254

SCNNlA-5406 + AGGUCAGCCUCACCCUC 17 9255

SCNNlA-5407 - CCAGUUCACCUGCCCUC 17 9256

SCNNlA-5408 - CUAGGGAAGCCCAGCUC 17 9257

SCNNlA-5409 + AUGGGGGAUCGGGGCUC 17 9258

SCNNlA-5410 - CUCCUAGCUGUGGGCUC 17 9259

SCNNlA-5411 + UGGAUUCGUCUGCUCUC 17 9260

SCNNlA-5412 - CCCCAUGAGUCUGUCUC 17 9261

SCNNlA-5413 - AGAGAUGACACCUUCUC 17 9262

SCNNlA-5414 - CCAGAGUCCGCCUUCUC 17 9263

SCNNlA-376 + UGGGGAGAGCAAGGGUC 17 4225

SCNNlA-5415 + AAUUGCAAUGCCUGGUC 17 9264

SCNNlA-5416 - AGGCCGCUGCACCUGUC 17 9265

SCNNlA-5417 + AGGAGUGGAGUGCCAAG 17 9266

SCNNlA-377 - CAGCUGUCCCUUCCAAG 17 4226

SCNNlA-5418 + CAGCGCUGGAAAGGAAG 17 9267

SCNNlA-5419 + ACCCGGAGCCCAGGAAG 17 9268

SCNNlA-5420 - UGGGGCCCGUGAGGAAG 17 9269

SCNNlA-378 - CUCCGGGGCUCAUGAAG 17 4227

SCNNlA-5421 + CCUCCCCGCUCACUAAG 17 9270

SCNNlA-5422 - UAAGUAGAUAGCCCCAG 17 9271

SCNNlA-5423 - CAUCCCUGGCCGGCCAG 17 9272

SCNNlA-5424 - CUCGAGGUCAGGGCCAG 17 9273

SCNNlA-379 - CCUCACUCGGGUUCCAG 17 4228

SCNNlA-5425 - CCCUAUCAGGGAAGCAG 17 9274

SCNNlA-5426 - CUCUGUGACCACAGCAG 17 9275

SCNNlA-5427 - UGGGAUAUGUGGGGCAG 17 9276

SCNNlA-5428 + AGGCGGACUCUGGGCAG 17 9277

SCNNlA-380 + CCUGGUAUGGGCUGCAG 17 4229

SCNNlA-5429 + UCACCUGACAGGUGCAG 17 9278

SCNNlA-5430 - AGAGACUGCCGCAAGAG 17 9279

SCNNlA-5431 - AGGGCCUAGAGUGAGAG 17 9280

SCNNlA-381 + CUUCAUGAGCCCCGGAG 17 4230

SCNNlA-5432 + UUGUCCAGACCCGGGAG 17 9281

SCNNlA-5433 - CAAGGCAAGGGGGGGAG 17 9282

1329

5535.1 SCNNlA-5434 - CAGCCGCAACCUGGGAG 17 9283

SCNNlA-5435 - UCUGGACAAGGUUGGAG 17 9284

SCNNlA-5436 - UGAGGGCCUAGAGUGAG 17 9285

SCNNlA-5437 - UGCUCCCACUUAGUGAG 17 9286

SCNNlA-5438 - AUGCUGCCUUAAGCUAG 17 9287

SCNNlA-5439 + UAAGAGCCAAGGGCUAG 17 9288

SCNNlA-5440 + AACCCAGGCCCUGCACG 17 9289

SCNNlA-5441 + AGCAUUGAUACACACCG 17 9290

SCNNlA-5442 + CUCCCACACAGAGCCCG 17 9291

SCNNlA-5443 + AGGAAGGAGGGCUCCCG 17 9292

SCNNlA-382 - CUCCCCAAUCCACUCCG 17 4231

SCNNlA-5444 - CUCCCACUUAGUGAGCG 17 9293

SCNNlA-5445 + CAACCAGAGGCAGCGCG 17 9294

SCNNlA-5446 + UAAAGGUGAGCAGGGCG 17 9295

SCNNlA-5447 + AGACUCAUGGGGGAUCG 17 9296

SCNNlA-5448 - AAU CAGG ACACAG CU CG 17 9297

SCNNlA-5449 + AGUUUUCCGAAGGAAGG 17 9298

SCNNlA-5450 + CUCACGGGCCCCACAGG 17 9299

SCNNlA-5451 + AAAGGUGAGCAGGGCGG 17 9300

SCNNlA-5452 + AUUAAAGGUGAGCAGGG 17 9301

SCNNlA-383 - AGAAUGUGGGCGCAGGG 17 4232

SCNNlA-5453 - AGCACCUUAUUGCAGGG 17 9302

SCNNlA-5454 + CUGGGUGGGGAACCGGG 17 9303

SCNNlA-5455 + CCUUGUCCAGACCCGGG 17 9304

SCNNlA-5456 - CCUGGCCGGCCAGCGGG 17 9305

SCNNlA-5457 + AAGGUGAGCAGGGCGGG 17 9306

SCNNlA-384 - CUGUCCCUUCCAAGGGG 17 4233

SCNNlA-5458 - CCACUUAGUGAGCGGGG 17 9307

SCNNlA-5459 + UUGAUACACACCGGGGG 17 9308

SCNNlA-5460 + CCUAGACAGGCCCUGGG 17 9309

SCNNlA-5461 + CUGAGACAGACUCAUGG 17 9310

SCNNlA-81 - CAUACCAGGUCUCAUGG 17 605

SCNNlA-5462 - UGAGACACAGAUCCUGG 17 9311

SCNNlA-5463 - UGUCUGCUGGCUUGUGG 17 9312

SCNNlA-5464 - CCUGUGGGUGCCCUUGG 17 9313

SCNNlA-5465 + ACAGAGUUGCAGGAAUG 17 9314

SCNNlA-5466 + CCUGAGACAGACUCAUG 17 9315

SCNNlA-5467 - UGUUGCCCUCCUAGCUG 17 9316

SCNNlA-5468 + UGUAAUCGCCCCUGCUG 17 9317

SCNNlA-385 + CCCCUGGAACCCGAGUG 17 4234

SCNNlA-5469 - CUCCUGUGGGGCCCGUG 17 9318

SCNNlA-5470 - AAUCCACGGGCUCUGUG 17 9319

1330

5535.1 SCNNlA-387 + AGCCCCGGAGUGGAUUG 17 4236

SCNNlA-5471 + UGUGGCUUCCUCUCUUG 17 9320

SCNNlA-5472 + CAGACCUGCGGGAGUUG 17 9321

SCNNlA-5473 + UCCUGAGACAGACUCAU 17 9322

SCNNlA-5474 + ACACCGGGGGAGGAGAU 17 9323

SCNNlA-5475 + ACAGACUCAUGGGGGAU 17 9324

SCNNlA-388 + UGAGCCCCGGAGUGGAU 17 4237

SCNNlA-5476 + UCCUCUGCUUCCCUGAU 17 9325

SCNNlA-389 - CGGGUUCCAGGGGUGAU 17 4238

SCNNlA-5477 + AGGAGAAAUUCGUUGAU 17 9326

SCNNlA-158 + UCCAUGAGACCUGGUAU 17 654

SCNNlA-5478 + CCGAGGGCAGGUGAACU 17 9327

SCNNlA-5479 - UCUCCUUGCUCACCACU 17 9328

SCNNlA-5480 + CAGGUUGCGGCUGGACU 17 9329

SCNNlA-5481 - CAGUCCAGCCGCAACCU 17 9330

SCNNlA-5482 - AGCCCCCAGCUUCACCU 17 9331

SCNNlA-5483 - UAGGCUCCCCUAGCCCU 17 9332

SCNNlA-5484 + ACGCCUAGACAGGCCCU 17 9333

SCNNlA-5485 - UGACCUGUGGGUGCCCU 17 9334

SCNNlA-5486 + AAGGGCUAGGGGAGCCU 17 9335

SCNNlA-5487 - UGCCGCGUGCAGGGCCU 17 9336

SCNNlA-5488 + AUCCUGAGCCCACAGCU 17 9337

SCNNlA-5489 + CCAAAAGUGCCGGAGCU 17 9338

SCNNlA-5490 + CAUAAGAGCCAAGGGCU 17 9339

SCNNlA-5491 - CCACAUUCCUGCACUCU 17 9340

SCNNlA-5492 + UUGCCCCCUCUCACUCU 17 9341

SCNNlA-5493 + CUGAGAAGGCGGACUCU 17 9342

SCNNlA-5494 - AGUUUCUAGGGGUCUCU 17 9343

SCNNlA-390 + AUGGGCUGCAGAGGUCU 17 4239

SCNNlA-5495 + AGGGCUCCAGGAGGUCU 17 9344

SCNNlA-5496 - AGAGGAGAGGCCGUUCU 17 9345

SCNNlA-5497 + CUAGAGGCUCAGCAAGU 17 9346

SCNNlA-5498 + CUCCCCGCUCACUAAGU 17 9347

SCNNlA-5499 + AGCAGACCUGCGGGAGU 17 9348

SCNNlA-5500 - AGCCGCAACCUGGGAGU 17 9349

SCNNlA-5501 - CCGGGUCUGGACAAGGU 17 9350

SCNNlA-5502 + AGUGAGUAGAGGCAGGU 17 9351

SCNNlA-5503 - UGCCUUAAGCUAGUGGU 17 9352

SCNNlA-5504 + CAGAGUUGCAGGAAUGU 17 9353

SCNNlA-5505 - UCUGGGCUGCCUCCUGU 17 9354

SCNNlA-5506 - AUCCACGGGCUCUGUGU 17 9355

SCNNlA-5507 + AGCCAGGUCCUUACAUU 17 9356

1331

5535.1 SCNNlA-5508 - CUCCUGGAAGCACACUU 17 9357

SCNNlA-5509 - UGGAGACAGACUCCCUU 17 9358

SCNNlA-5510 - UUUUGCUGCAUUAAGUU 17 9359

SCNNlA-392 - AGCAAGGGAACCUGGUU 17 4241

SCNNlA-5511 - CCCAGCUCCGGCACUUU 17 9360

SCNNlA-5512 - UCUCCUCCAGCCCUUUU 17 9361

SCNNlA-5513 - CUCCUCCAGCCCUUUUU 17 9362

SCNNlA-5514 + UCAGAGAAUCAGACCCAAAA 20 9363

SCNNlA-5515 + UAGAAGGAGCCAGCACCAAA 20 9364

SCNNlA-5516 - CAUGAGCUGGCAAAUAGAAA 20 9365

SCNNlA-5517 + AUCUCCUUGGCUCUGUGAAA 20 9366

SCNNlA-5518 + AUAGAAGGAGCCAGCACCAA 20 9367

SCNNlA-5519 - UCCUGGAGGAAGAAGACCAA 20 9368

SCNNlA-5520 + AGAUAAGACAUAAGAGCCAA 20 9369

SCNNlA-5521 - AAUCCAGCUGUCCCUUCCAA 20 9370

SCNNlA-393 - AG C AG U A U C A AG G U A AG C A A 20 4242

SCNNlA-5522 - AAUGUAAGGACCUGGCUCAA 20 9371

SCNNlA-5523 + CCCUGGCUGUUUGAUCUCAA 20 9372

SCNNlA-5524 - AGGUCUGCUGGCUCCAGGAA 20 9373

SCNNlA-5525 - AACUGAUUUAUCCUUGGGAA 20 9374

SCNNlA-394 + CAUGAUACCUCCCCUUGGAA 20 4243

SCNNlA-5526 + CUCAUUAGCAUCUCAAUUAA 20 9375

SCNNlA-5527 + ACAGCUAGGAGGGCAACACA 20 9376

SCNNlA-395 - UGUGGGCGCAGGGUGGGACA 20 4244

SCNNlA-5528 - CCUUUGAGAUCAAACAGCCA 20 9377

SCNNlA-5529 - CCAGAG AGCAGACGAAU CCA 20 9378

SCNNlA-5530 + AGCAAGUGGGCAGCCCUCCA 20 9379

SCNNlA-5531 - AAAUCCAGCUGUCCCUUCCA 20 9380

SCNNlA-5532 + CUGCUGAAUCUUGACAAGCA 20 9381

SCNNlA-5533 + UGUCUCCAGGAAGGAGAGCA 20 9382

SCNNlA-5534 + AUCUCAAUUAAAGGUGAGCA 20 9383

SCNNlA-396 - AGUGGGAGAAUGUGGGCGCA 20 4245

SCNNlA-5535 + CCGGAGCCCAGGAAGAGGCA 20 9384

SCNNlA-5536 + CCCAGGCCCUGCACGCGGCA 20 9385

SCNNlA-5537 + CCAGGUCCUUACAUUGGGCA 20 9386

SCNNlA-5538 - AGCCUUCCCUGCCGCGUGCA 20 9387

SCNNlA-5539 + AAG C AGG CAC U G AAG G U G C A 20 9388

SCNNlA-5540 - CUCGAAAGGUGGCCCUAUCA 20 9389

SCNNlA-397 - AGGUAUCAUGAGCAGUAUCA 20 4246

SCNNlA-5541 + AAGGCAGUACUCCAGGCUCA 20 9390

SCNNlA-5542 - CAAUGUAAGGACCUGGCUCA 20 9391

SCNNlA-398 + AUUGGGGAGAGCAAGGGUCA 20 4247

1332

5535.1 SCNNlA-5543 + UGGGAGUACUGGACCUGAGA 20 9392

SCNNlA-5544 + CAGAGCCGGGAGUUUUCCGA 20 9393

SCNNlA-5545 + ACAAUAGAGAGGGACAGCGA 20 9394

SCNNlA-5546 + AAGGGAGUCUGUCUCCAGGA 20 9395

SCNNlA-5547 + UCCUGAGCCCACAGCUAGGA 20 9396

SCNNlA-5548 + AACCUUGUCCAGACCCGGGA 20 9397

SCNNlA-5549 + CCUGGAUGUGAAAGCCGGGA 20 9398

SCNNlA-5550 - AGAUGACACCUUCUCUGGGA 20 9399

SCNNlA-5551 - AAACUGAUUUAUCCUUGGGA 20 9400

SCNNlA-3 - CCCAUACCAGGUCUCAUGGA 20 556

SCNNlA-5552 - UUUGUCUGCUGGCUUGUGGA 20 9401

SCNNlA-399 + UCAUGAUACCUCCCCUUGGA 20 4248

SCNNlA-5553 - CGGGUCUGGACAAGGUUGGA 20 9402

SCNNlA-400 - AUCCACUCCGGGGCUCAUGA 20 4249

SCNNlA-5554 - CUCUUCUCUGCAGGGCCUGA 20 9403

SCNNlA-5555 - CGGGCUCUGUGUGGGAGUGA 20 9404

SCNNlA-5556 - CCGCUGCACCUGUCAGGUGA 20 9405

SCNNlA-401 - CACUCGGGUUCCAGGGGUGA 20 4250

SCNNlA-5557 + UCUCCUCUGCUUCCCUGAUA 20 9406

SCNNlA-5558 - AAGGGAGACUGGAGUUUCUA 20 9407

SCNNlA-78 + CCCCUCCAUGAGACCUGGUA 20 500

SCNNlA-5559 - UUUGGAAUCCUGGUUGACAC 20 9408

SCNNlA-5560 + AGCCCUCCAAGGGCACCCAC 20 9409

SCNNlA-5561 + CGCUUCCUCACGGGCCCCAC 20 9410

SCNNlA-5562 - CAGAGAGCAGACGAAUCCAC 20 9411

SCNNlA-5563 + CAGGGGCUUUAGACGCAGAC 20 9412

SCNNlA-5564 + CGGCCAGGGAUGGAAGCGAC 20 9413

SCNNlA-5565 + CUCCCAGGUUGCGGCUGGAC 20 9414

SCNNlA-5566 + UCCAGGCUCAGGGUCCAACC 20 9415

SCNNlA-5567 + AGUGAAAGCCGGUGUCAACC 20 9416

SCNNlA-404 - U C A AG G U A AG C A AG G G A AC C 20 4253

SCNNlA-5568 + CCUGAGCAUUGAUACACACC 20 9417

SCNNlA-5569 + CCUCCAACCUUGUCCAGACC 20 9418

SCNNlA-5570 - CCAUGCCCAAUGUAAGGACC 20 9419

SCNNlA-5571 - AGCAGGAAAGAGGAGGGACC 20 9420

SCNNlA-405 - AGACCUCUGCAGCCCAUACC 20 4254

SCNNlA-5572 + CUCCAACCUUGUCCAGACCC 20 9421

SCNNlA-406 + AACCCGAGUGAGGCUGCCCC 20 4255

SCNNlA-5573 + CCUGAUUCUGUCUCUGCCCC 20 9422

SCNNlA-5574 - UGCAGGCCUAUCUCCUCCCC 20 9423

SCNNlA-5575 + UGGACACAGACCCGGAGCCC 20 9424

SCNNlA-5576 - AUUCCUGUCGCUUCCAUCCC 20 9425

1333

5535.1 SCNNlA-5577 - AACGAAUUUCUCCUCCUCCC 20 9426

SCNNlA-5578 - ACCUUUGAGAUCAAACAGCC 20 9427

SCNNlA-5579 - AGCGGGCGGGCUCCCCAGCC 20 9428

SCNNlA-5580 + ACAAGGAGAAGGGGCCAGCC 20 9429

SCNNlA-5581 - ACCAGGUUGGACCCUGAGCC 20 9430

SCNNlA-5582 + ACUCCAGUCUCCCUUGAGCC 20 9431

SCNNlA-5583 + ACACUGUUGGCUGCCAGGCC 20 9432

SCNNlA-5584 + ACCUGACAGGUGCAGCGGCC 20 9433

SCNNlA-5585 - UCCCUGCCGCGUGCAGGGCC 20 9434

SCNNlA-5586 + UUUUUACACUGUUGGCUGCC 20 9435

SCNNlA-5587 - CCUUCCCGGCUUUCACAUCC 20 9436

SCNNlA-5588 - AGGAGCUGAGACACAGAUCC 20 9437

SCNNlA-5589 - UCCUUCCUUCGGAAAACUCC 20 9438

SCNNlA-408 - UGCUCUCCCCAAUCCACUCC 20 4257

SCNNlA-8 - AGCCCUCCACAGUCCACUCC 20 559

SCNNlA-5590 + AAGAGAAAAGGCAGUACUCC 20 9439

SCNNlA-5591 - UGGAGGCAGCCCAGACCUCC 20 9440

SCNNlA-5592 - AGCUUCACCUGGGCCCCUCC 20 9441

SCNNlA-5593 - UUUCUGCCCUCCUGUCCUCC 20 9442

SCNNlA-5594 - CUUGCUGAGCCUCUAGCUCC 20 9443

SCNNlA-5595 - CCCGCAGGUCUGCUGGCUCC 20 9444

SCNNlA-5596 + ACCAAAGGGAGUCUGUCUCC 20 9445

SCNNlA-5597 - CAGGGGCGAUUACACAUUCC 20 9446

SCNNlA-5598 - UCCCCCCUUGCUCUCCUUCC 20 9447

SCNNlA-5 - UCUCAUGGAGGGGAACAAGC 20 557

SCNNlA-5599 - UGCAACUCUGUGACCACAGC 20 9448

SCNNlA-409 + CUCCCCUUGGAAGGGACAGC 20 4258

SCNNlA-5600 - UCCAUCCCUGGCCGGCCAGC 20 9449

SCNNlA-5601 + CAUCUCAAUUAAAGGUGAGC 20 9450

SCNNlA-5602 + UGACAAGCAAGGAGUUUAGC 20 9451

SCNNlA-5603 + AGGCAGCGCGAGGGCCACGC 20 9452

SCNNlA-5604 + UGGCUGGGGAGCCCGCCCGC 20 9453

SCNNlA-5605 - CUUUUGGCCCCAACUCCCGC 20 9454

SCNNlA-5606 - ACCCUCUUCCUUUCCAGCGC 20 9455

SCNNlA-5607 - UCGAGGUCAGGGCCAGAGGC 20 9456

SCNNlA-5608 + ACGCAGACAGGCAAGGAGGC 20 9457

SCNNlA-5609 + ACCCAGGCCCUGCACGCGGC 20 9458

SCNNlA-5610 + UCCCACUCCCAGGUUGCGGC 20 9459

SCNNlA-5611 + CAAUUAAAGGUGAGCAGGGC 20 9460

SCNNlA-5612 - UCCCUGGCCGGCCAGCGGGC 20 9461

SCNNlA-5613 + UGAGAAGGCGGACUCUGGGC 20 9462

SCNNlA-5614 - CUGUCGCUUCCAUCCCUGGC 20 9463

1334

5535.1 SCNNlA-5615 + CCUGGAGCCAGCAGACCUGC 20 9464

SCNNlA-5616 + AAGAGAGAAGAGGUCUCUGC 20 9465

SCNNlA-5617 - CCCAACUCCCGCAGGUCUGC 20 9466

SCNNlA-5618 - CAGGCUGGGCCUUUGUCUGC 20 9467

SCNNlA-5619 - CAGCCUUCCCUGCCGCGUGC 20 9468

SCNNlA-5620 + A A AG CAGGCACUGAAGGUGC 20 9469

SCNNlA-5621 + UUCGUCUGCUCUCUGGGUGC 20 9470

SCNNlA-5622 - ACCUUAUCUUAUUGUAUUGC 20 9471

SCNNlA-5623 + UGCUGUGGUCACAGAGUUGC 20 9472

SCNNlA-5624 - CCUGGGGCAGAGACAGAAUC 20 9473

SCNNlA-5625 + AGACAGACUCAUGGGGGAUC 20 9474

SCNNlA-5626 - ACUCGAAAGGUGGCCCUAUC 20 9475

SCNNlA-410 - UUGCUCUCCCCAAUCCACUC 20 4259

SCNNlA-5627 + UAAGUGGGAGCAGCGCACUC 20 9476

SCNNlA-5628 + AAAAGGGCUGGAGGAGACUC 20 9477

SCNNlA-5629 + CACAGGUCAGCCUCACCCUC 20 9478

SCNNlA-5630 - CGUGGCCCUCGCGCUGCCUC 20 9479

SCNNlA-411 + UCAGGGUCAAGGCUGAGCUC 20 4260

SCNNlA-5631 + AAAGGCAGUACUCCAGGCUC 20 9480

SCNNlA-5632 + CUCAUGGGGGAUCGGGGCUC 20 9481

SCNNlA-5633 - CCCGGUGUGUAUCAAUGCUC 20 9482

SCNNlA-5634 + CCGUGGAUUCGUCUGCUCUC 20 9483

SCNNlA-5635 - CUGGAGUUUCUAGGGGUCUC 20 9484

SCNNlA-5636 - AUCCCCCAUGAGUCUGUCUC 20 9485

SCNNlA-5637 - AGCAGAGAUGACACCUUCUC 20 9486

SCNNlA-5638 - UGCCCAGAGUCCGCCUUCUC 20 9487

SCNNlA-5639 - UCAGGACACAGCUCGAGGUC 20 9488

SCNNlA-5640 + AAGAAUUGCAAUGCCUGGUC 20 9489

SCNNlA-5641 - UAAGCUAGUGGUUGGAUUUC 20 9490

SCNNlA-5642 + AUAAGGAGUGGAGUGCCAAG 20 9491

SCNNlA-412 - AUCCAGCUGUCCCUUCCAAG 20 4261

SCNNlA-5643 + CAGACCCGGAGCCCAGGAAG 20 9492

SCNNlA-5644 - CUGUGGGGCCCGUGAGGAAG 20 9493

SCNNlA-5645 + UCUCCUCCCCGCUCACUAAG 20 9494

SCNNlA-5646 - CGCUAAGUAGAUAGCCCCAG 20 9495

SCNNlA-5647 - UUCCAUCCCUGGCCGGCCAG 20 9496

SCNNlA-5648 - CAGCUCGAGGUCAGGGCCAG 20 9497

SCNNlA-413 - UGGGACAUGGGCAUGGCCAG 20 4262

SCNNlA-414 - CAGCCUCACUCGGGUUCCAG 20 4263

SCNNlA-5649 - UGGCCCUAUCAGGGAAGCAG 20 9498

SCNNlA-5650 - CAACUCUGUGACCACAGCAG 20 9499

SCNNlA-5651 - CUCUGGGAUAUGUGGGGCAG 20 9500

1335

5535.1 SCNNlA-5652 + AGAAGGCGGACUCUGGGCAG 20 9501

SCNNlA-415 + AGACCUGGUAUGGGCUGCAG 20 4264

SCNNlA-5653 - CUGAGGGCCUAGAGUGAGAG 20 9502

SCNNlA-5654 + UGCAGCAAAAGGAUAAGGAG 20 9503

SCNNlA-5655 + ACCUUGUCCAGACCCGGGAG 20 9504

SCNNlA-4 - CCAUACCAGGUCUCAUGGAG 20 498

SCNNlA-5656 + AAGGGGCCAGCCAGGCUGAG 20 9505

SCNNlA-5657 - AGCUGAGGGCCUAGAGUGAG 20 9506

SCNNlA-5658 - CGCUGCUCCCACUUAGUGAG 20 9507

SCNNlA-5659 - CGCUGCACCUGUCAGGUGAG 20 9508

SCNNlA-5660 + CAAGGGCUAGGGGAGCCUAG 20 9509

SCNNlA-5661 + AGUGUGCUUCCAGGAGCUAG 20 9510

SCNNlA-5662 + ACAUAAGAGCCAAGGGCUAG 20 9511

SCNNlA-5663 - AGGGAGACUGGAGUUUCUAG 20 9512

SCNNlA-5664 + CACAACCCAGGCCCUGCACG 20 9513

SCNNlA-5665 + CUGAGCAUUGAUACACACCG 20 9514

SCNNlA-5666 + UCACUCCCACACAGAGCCCG 20 9515

SCNNlA-5667 + CGAAGGAAGGAGGGCUCCCG 20 9516

SCNNlA-5668 - CUGCUCCCACUUAGUGAGCG 20 9517

SCNNlA-5669 + AAUUAAAGGUGAGCAGGGCG 20 9518

SCNNlA-5670 - CAAGGUUGGAGGGGGUGGCG 20 9519

SCNNlA-5671 - UGUGUCCACAGUGUCCUGCG 20 9520

SCNNlA-5672 - CAGAAUCAGGACACAGCUCG 20 9521

SCNNlA-5673 - CUAGGACAAAACUCGAAAGG 20 9522

SCNNlA-5674 + UUAGACGCAGACAGGCAAGG 20 9523

SCNNlA-5675 + UUCCUCACGGGCCCCACAGG 20 9524

SCNNlA-5676 + UGGGGAACCGGGAGGACAGG 20 9525

SCNNlA-5677 + ACUGAGUGAGUAGAGGCAGG 20 9526

SCNNlA-5678 - UAAGUAGAUAGCCCCAGAGG 20 9527

SCNNlA-5679 - UGAGGGCCUAGAGUGAGAGG 20 9528

SCNNlA-5680 + AUCCUGAGCCCACAGCUAGG 20 9529

SCNNlA-5681 + AGGUGAAGCUGGGGGCUAGG 20 9530

SCNNlA-5682 + UGAGCAUUGAUACACACCGG 20 9531

SCNNlA-5683 + AUUAAAGGUGAGCAGGGCGG 20 9532

SCNNlA-5684 + CAGGCACUGAAGGUGCAGGG 20 9533

SCNNlA-5685 - CUGAGCACCUUAUUGCAGGG 20 9534

SCNNlA-5686 + CAACCUUGUCCAGACCCGGG 20 9535

SCNNlA-5687 - AUCCCUGGCCGGCCAGCGGG 20 9536

SCNNlA-5688 + UUAAAGGUGAGCAGGGCGGG 20 9537

SCNNlA-416 - CAGCUGUCCCUUCCAAGGGG 20 4265

SCNNlA-5689 - CUCCCACUUAGUGAGCGGGG 20 9538

SCNNlA-5690 - CUGGACAAGGUUGGAGGGGG 20 9539

1336

5535.1 SCNNlA-5691 + ACGCCUAGACAGGCCCUGGG 20 9540

SCNNlA-5692 + UUCCUGAGACAGACUCAUGG 20 9541

SCNNlA-5693 - AGCUGAGACACAGAUCCUGG 20 9542

SCNNlA-5694 + UCAGACCCAAAAAGGGCUGG 20 9543

SCNNlA-75 + AGCCCUGGAGUGGACUGUGG 20 602

SCNNlA-5695 - CUUUGUCUGCUGGCUUGUGG 20 9544

SCNNlA-5696 - UGACCUGUGGGUGCCCUUGG 20 9545

SCNNlA-5697 - CCGGGUCUGGACAAGGUUGG 20 9546

SCNNlA-5698 + CUUCCUGAGACAGACUCAUG 20 9547

SCNNlA-5699 + CUGAAGGUGCAGGGAGGAUG 20 9548

SCNNlA-5700 - CUAGGGGUCUCUGGGAUAUG 20 9549

SCNNlA-5701 + UCCUGGAGCCAGCAGACCUG 20 9550

SCNNlA-5702 - CUGAGGGUGAGGCUGACCUG 20 9551

SCNNlA-5703 - UCUCUUCUCUGCAGGGCCUG 20 9552

SCNNlA-5704 - UUGUGUUGCCCUCCUAGCUG 20 9553

SCNNlA-5705 + CAGGUGCAGCGGCCUGGCUG 20 9554

SCNNlA-5706 + AUGUGUAAUCGCCCCUGCUG 20 9555

SCNNlA-5707 + AGAAUUCUCCUCCUCCUCUG 20 9556

SCNNlA-5708 + UCAGGGUCCAACCUGGUCUG 20 9557

SCNNlA-5709 + AAGGAUAAAUCAGUUUUCUG 20 9558

SCNNlA-5710 - CUGGGAUAUGUGGGGCAGUG 20 9559

SCNNlA-417 + UCACCCCUGGAACCCGAGUG 20 4266

SCNNlA-5711 - ACGGGCUCUGUGUGGGAGUG 20 9560

SCNNlA-5712 - UGCCUCCUGUGGGGCCCGUG 20 9561

SCNNlA-5713 + UGAGUGAGUAGAGGCAGGUG 20 9562

SCNNlA-5714 - CUCUGCAGGGCCUGAGGGUG 20 9563

SCNNlA-5715 - AGGGGUCUCUGGGAUAUGUG 20 9564

SCNNlA-5716 - ACUCUGGGCUGCCUCCUGUG 20 9565

SCNNlA-5717 - ACGAAUCCACGGGCUCUGUG 20 9566

SCNNlA-5718 - CGUGCAGGGCCUGGGUUGUG 20 9567

SCNNlA-419 + AUGAGCCCCGGAGUGGAUUG 20 4268

SCNNlA-5719 + CAGCAGACCUGCGGGAGUUG 20 9568

SCNNlA-5720 + CUGAGGUUAGAAAACAAAAU 20 9569

SCNNlA-5721 + CUUGAGCCAGGUCCUUACAU 20 9570

SCNNlA-5722 + ACAGCGAAGGACAGAGAGAU 20 9571

SCNNlA-5723 + UACACACCGGGGGAGGAGAU 20 9572

SCNNlA-420 + UCAUGAGCCCCGGAGUGGAU 20 4269

SCNNlA-5724 + CUCUCCUCUGCUUCCCUGAU 20 9573

SCNNlA-421 - ACUCGGGUUCCAGGGGUGAU 20 4270

SCNNlA-5725 + AGGAGGAGAAAUUCGUUGAU 20 9574

SCNNlA-79 + CCCUCCAUGAGACCUGGUAU 20 604

SCNNlA-5726 + CUCCCGAGGGCAGGUGAACU 20 9575

1337

5535.1 SCNNlA-5727 - CUAGCUCCUGGAAGCACACU 20 9576

SCNNlA-5728 - CUCUCUCCUUGCUCACCACU 20 9577

SCNNlA-5729 + AAAAAGGGCUGGAGGAGACU 20 9578

SCNNlA-5730 + UCCCAGGUUGCGGCUGGACU 20 9579

SCNNlA-5731 - UCCCAGUCCAGCCGCAACCU 20 9580

SCNNlA-5732 - CCUAGCCCCCAGCUUCACCU 20 9581

SCNNlA-5733 - CCCUAGGCUCCCCUAGCCCU 20 9582

SCNNlA-5734 + CACACGCCUAGACAGGCCCU 20 9583

SCNNlA-5735 + UGGGGGCUAGGCGGGGCCCU 20 9584

SCNNlA-5736 - ACUCCCAGUUCACCUGCCCU 20 9585

SCNNlA-5737 - CCCUGCCGCGUGCAGGGCCU 20 9586

SCNNlA-5738 + UGGGUGCUGGGUUAUCUCCU 20 9587

SCNNlA-5739 - UCCUGGAGCCCUGCAGUCCU 20 9588

SCNNlA-5740 + AGGAUCCUGAGCCCACAGCU 20 9589

SCNNlA-5741 - UGUGUAUCAAUGCUCAGGCU 20 9590

SCNNlA-5742 + CGCAGACAGGCAAGGAGGCU 20 9591

SCNNlA-5743 + AGACAUAAGAGCCAAGGGCU 20 9592

SCNNlA-5744 + ACAGGUGCAGCGGCCUGGCU 20 9593

SCNNlA-5745 + UCGUCUGCUCUCUGGGUGCU 20 9594

SCNNlA-5746 - UGACCACAUUCCUGCACUCU 20 9595

SCNNlA-422 + CAGGGUCAAGGCUGAGCUCU 20 4271

SCNNlA-5747 + CGUGGAUUCGUCUGCUCUCU 20 9596

SCNNlA-5748 - UGGAGUUUCUAGGGGUCUCU 20 9597

SCNNlA-5749 + UGCAGGGCUCCAGGAGGUCU 20 9598

SCNNlA-5750 - AGCAGAGGAGAGGCCGUUCU 20 9599

SCNNlA-5751 - CAAGGGAGACUGGAGUUUCU 20 9600

SCNNlA-5752 + CUCCUCCCCGCUCACUAAGU 20 9601

SCNNlA-5753 - UCUGGGAUAUGUGGGGCAGU 20 9602

SCNNlA-5754 - UCCAGCCGCAACCUGGGAGU 20 9603

SCNNlA-5755 - CUCCCGGGUCUGGACAAGGU 20 9604

SCNNlA-5756 + CUGAGUGAGUAGAGGCAGGU 20 9605

SCNNlA-5757 + UGGGAGCAGCGCACUCAGGU 20 9606

SCNNlA-5758 - UGCUGCCUUAAGCUAGUGGU 20 9607

SCNNlA-5759 - AGGGAGGAGUGGGAGAAUGU 20 9608

SCNNlA-5760 + U C ACAG AG U U G CAG G AA U G U 20 9609

SCNNlA-5761 - UAGGGGUCUCUGGGAUAUGU 20 9610

SCNNlA-5762 + UCUGUUCUUUUUUACACUGU 20 9611

SCNNlA-5763 - UGAGGGUGAGGCUGACCUGU 20 9612

SCNNlA-5764 - CACUCUGGGCUGCCUCCUGU 20 9613

SCNNlA-5765 - UGUGUUGCCCUCCUAGCUGU 20 9614

SCNNlA-5766 - CGAAUCCACGGGCUCUGUGU 20 9615

SCNNlA-5767 + UUGAGCCAGGUCCUUACAUU 20 9616

1338

5535.1 SCNNlA-425 + CAUGAGCCCCGGAGUGGAUU 20 4274

SCNNlA-5768 - UAGCUCCUGGAAGCACACUU 20 9617

SCNNlA-5769 - UCCUGGAGACAGACUCCCUU 20 9618

SCNNlA-5770 - CUCGGGAGCCCUCCUUCCUU 20 9619

SCNNlA-5771 - UCCUUUUGCUGCAUUAAGUU 20 9620

SCNNlA-5772 + CCAGCAGACCUGCGGGAGUU 20 9621

SCNNlA-5773 - U UAAG U U UGG AAAG AG AU U U 20 9622

SCNNlA-5774 - AAGCCCAGCUCCGGCACUUU 20 9623

SCNNlA-5775 - AGUCUCCUCCAGCCCUUUUU 20 9624

Table 46C provides exemplary targeting domains for knocking down the SCNN1A gene selected according to the third tier parameters. The targeting domains bind within 500 bp (e.g., upstream or downstream) of a transcription start site (TSS) and start with a 5'G. It is

contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. pyogenes eiCas9 molecule or eiCas9 fusion protein (e.g., an eiCas9 fused to a transcription repressor domain) to alter the SCNN1A gene (e.g., reduce or eliminate SCNN1A gene expression, SCNN1A protein function, or the level of SCNN1A protein). One or more gRNA may be used to target an eiCas9 to the promoter region of the SCNN1A gene

Table 46C

1339

5535.1 SCNNlA-5788 - GAAAGGUGGAGGAGGGA 17 9637

SCNNlA-5789 + GGACAGAGAGAUAGGGA 17 9638

SCNNlA-5790 + GGGAAAGCAGGCACUGA 17 9639

SCNNlA-5791 + GACAGGAUGGCAGGUGA 17 9640

SCNNlA-5792 + GGGCCUGGGUGGGGAAC 17 9641

SCNNlA-5793 + GGCCUGGGUGGGGAACC 17 9642

SCNNlA-5794 - GAAUUUCUCCUCCUCCC 17 9643

SCNNlA-5795 + GAGGAGGAGUCAGAGCC 17 9644

SCNNlA-5796 + GCCAGGCUGAGAGGGCC 17 9645

SCNNlA-429 - GGGACAUGGGCAUGGCC 17 4278

SCNNlA-5797 - GCCUCUUCCUGGGCUCC 17 9646

SCNNlA-5798 - GCAGGUCUGCUGGCUCC 17 9647

SCNNlA-5799 + GAAGAGGCAGGG A A AG C 17 9648

SCNNlA-5800 - GCCAGAAAGAGGAGAGC 17 9649

SCNNlA-86 - GAACAAGCUGGAGGAGC 17 531

SCNNlA-5801 - GGAUUUCAGGCAUGAGC 17 9650

SCNNlA-5802 - GCUCCCACUUAGUGAGC 17 9651

SCNNlA-5803 + GGAGCCCAGGAAGAGGC 17 9652

SCNNlA-5804 - GGGAGAGGAAGAGAGGC 17 9653

SCNNlA-5805 - GAGAGGGAGUGAGAGGC 17 9654

SCNNlA-5806 - GAUUAGAGAGAGGAGGC 17 9655

SCNNlA-5807 - GGCUUGUGGAGGGAGGC 17 9656

SCNNlA-5808 + GGAGGGCUCCCGAGGGC 17 9657

SCNNlA-5809 - GGCCCUCUCAGCCUGGC 17 9658

SCNNlA-5810 + GAGGCAGCCCAGAGUGC 17 9659

SCNNlA-5811 + GAAUUCUCCUCCUCCUC 17 9660

SCNNlA-430 + GGGUCAAGGCUGAGCUC 17 4279

SCNNlA-5812 - GGAGGCAGGCCAG A A AG 17 9661

SCNNlA-5813 + GACAGGAGGGCAGAAAG 17 9662

SCNNlA-5814 + GGCAACACAAGGAGAAG 17 9663

SCNNlA-5815 - GGGGGGGAGAGGAAGAG 17 9664

SCNNlA-5816 + GGUGAGCAAGGAGAGAG 17 9665

SCNNlA-5817 - GAGGCAGGAUUAGAGAG 17 9666

SCNNlA-5818 - GAGGAGGGAGGGAGGAG 17 9667

SCNNlA-5819 + GAGCAGGGCGGGGGGAG 17 9668

SCNNlA-5820 + GGGCCAGCCAGGCUGAG 17 9669

SCNNlA-5821 - GAUAGAGAGGGAGUGAG 17 9670

SCNNlA-5822 - GGUUGGAGGGGGUGGCG 17 9671

SCNNlA-5823 - GCUGGCUCCAGGAAAGG 17 9672

SCNNlA-5824 - GAGGGGGCAAGGCAAGG 17 9673

SCNNlA-5825 + GACUGCAGGGCUCCAGG 17 9674

SCNNlA-5826 + GAGUGAGUAGAGGCAGG 17 9675

1340

5535.1 SCNNlA-5827 + GAGCAAGGAGAGAGAGG 17 9676

SCNNlA-5828 - GCAGGAUUAGAGAGAGG 17 9677

SCNNlA-5829 - GAGGAGGGACCAGGAGG 17 9678

SCNNlA-5830 - GAUAGCCCCAGAGGAGG 17 9679

SCNNlA-5831 + GGGGGGAGGGGCUGAGG 17 9680

SCNNlA-5832 - GCACCUGUCAGGUGAGG 17 9681

SCNNlA-5833 - GGCAGAGACAGAAAGGG 17 9682

SCNNlA-5834 + GCUGGAAAGGAAGAGGG 17 9683

SCNNlA-5835 - GGAAAGGUGGAGGAGGG 17 9684

SCNNlA-5836 - GGGGGCAAGGCAAGGGG 17 9685

SCNNlA-5837 - GACAAGGUUGGAGGGGG 17 9686

SCNNlA-5838 + GUGAGCAGGGCGGGGGG 17 9687

SCNNlA-5839 + GGCUGAGAGGGCCUGGG 17 9688

SCNNlA-5840 + GAGUAGAGGCAGGUGGG 17 9689

SCNNlA-5841 - GGCCUGGGUUGUGUGGG 17 9690

SCNNlA-431 - GAAGGGGAACAAGCUGG 17 4280

SCNNlA-85 - GGAGGGGAACAAGCUGG 17 530

SCNNlA-5842 + GGCCCAGGUGAAGCUGG 17 9691

SCNNlA-5843 - GGCUCCAGGAAAGGUGG 17 9692

SCNNlA-5844 + GUGGGGGGCAGUGGUGG 17 9693

SCNNlA-5845 - GGAGGAGUGGGAGAAUG 17 9694

SCNNlA-5846 - GGAGCCCUGCAGUCCUG 17 9695

SCNNlA-5847 + GGGCCCAGGUGAAGCUG 17 9696

SCNNlA-5848 - GCCAGAGGCUGGAGCUG 17 9697

SCNNlA-5849 + GACAGGCAAGGAGGCUG 17 9698

SCNNlA-5850 + GGCGGGGGGAGGGGCUG 17 9699

SCNNlA-5851 - GGAUAUGUGGGGCAGUG 17 9700

SCNNlA-5852 - GGCUCUGUGUGGGAGUG 17 9701

SCNNlA-5853 + GGACAGGAUGGCAGGUG 17 9702

SCNNlA-5854 + GGUGGGGGGCAGUGGUG 17 9703

SCNNlA-5855 - GCAGGGCCUGGGUUGUG 17 9704

SCNNlA-5856 - GCUCCUGGAAGCACACU 17 9705

SCNNlA-5857 + GGGGCCCAGGUGAAGCU 17 9706

SCNNlA-5858 - GAAGCCACAGACCAGGU 17 9707

SCNNlA-5859 + GCUGAGAGGGCCUGGGU 17 9708

SCNNlA-5860 - GAGGAGUGGGAGAAUGU 17 9709

SCNNlA-5861 - GAGGGGGAGGAGAGGUU 17 9710

SCNNlA-5862 + GCCUUCUGUUUCUCUUU 17 9711

SCNNlA-5863 - GAAGGGGGCAGAGACAGAAA 20 9712

SCNNlA-432 + GAGUGGAUUGGGGAGAGCAA 20 4281

SCNNlA-5864 - GGAAGGGGGCAGAGACAGAA 20 9713

SCNNlA-5865 - GAGGAAGAAGACCAAAGGAA 20 9714

1341

5535.1 SCNNlA-5866 - G AG ACCU U U U CACAG AG CCA 20 9715

SCNNlA-9 - GCCCUCCACAGUCCACUCCA 20 499

SCNNlA-5867 - GCAACUCUGUGACCACAGCA 20 9716

SCNNlA-433 + GGAGUGGAUUGGGGAGAGCA 20 4282

SCNNlA-5868 - GAGUGAGAGGGGGCAAGGCA 20 9717

SCNNlA-5869 + GGAAAGGAAGAGGGUGGGCA 20 9718

SCNNlA-5870 + GUCUCUGCCCCAGGACUGCA 20 9719

SCNNlA-434 + GAGAGCAAGGGUCAGGGUCA 20 4283

SCNNlA-5871 - GAGACCCAAAGAGAAACAGA 20 9720

SCNNlA-435 - GUUCCAGGGGUGAUGGGAGA 20 4284

SCNNlA-5872 + GAAGGAAGGAGGGCUCCCGA 20 9721

SCNNlA-5873 - GGAGGAAGAAGACCAAAGGA 20 9722

SCNNlA-5874 + GGGGAACCGGGAGGACAGGA 20 9723

SCNNlA-5875 - G G A A U C AG C AG G A A AG AG G A 20 9724

SCNNlA-5876 + GUGAGCAAGGAGAGAGAGGA 20 9725

SCNNlA-5877 - GCUCCAGGAAAGGUGGAGGA 20 9726

SCNNlA-5878 + GAAGGACAGAGAGAUAGGGA 20 9727

SCNNlA-5879 + G C AGG G AAAG CAG G C AC U G A 20 9728

SCNNlA-5880 - GGGCCAGAGGCUGGAGCUGA 20 9729

SCNNlA-5881 + GGGGACAGGAUGGCAGGUGA 20 9730

SCNNlA-5882 + GAGAGCCACCCACACAACCC 20 9731

SCNNlA-5883 + GCCUCCAGCUUCCCACUCCC 20 9732

SCNNlA-5884 - GGGAGUGAGGGAGGCCUUCC 20 9733

SCNNlA-5885 + GGGAGGGGCCCAGGUGAAGC 20 9734

SCNNlA-5886 + GGCUGAGGAGGAGUCAGAGC 20 9735

SCNNlA-7 - GGGGAACAAGCUGGAGGAGC 20 504

SCNNlA-5887 + GGGGCCAAAAGUGCCGGAGC 20 9736

SCNNlA-5888 - GUUGGAUUUCAGGCAUGAGC 20 9737

SCNNlA-5889 - GGGGGGAGAGGAAGAGAGGC 20 9738

SCNNlA-5890 + GGCACUGAGUGAGUAGAGGC 20 9739

SCNNlA-5891 - GCUGGCUUGUGGAGGGAGGC 20 9740

SCNNlA-5892 + GGUGAAGCUGGGGGCUAGGC 20 9741

SCNNlA-5893 - GUGACCACAUUCCUGCACUC 20 9742

SCNNlA-5894 + GAGGACAGGAGGGCAGAAAG 20 9743

SCNNlA-5895 + GAGGGCAACACAAGGAGAAG 20 9744

SCNNlA-5896 + GAAAGAGGGAGACAAUAGAG 20 9745

SCNNlA-5897 - GUGGAGGAGGGAGGGAGGAG 20 9746

SCNNlA-5898 + GAGAGAUAGGGAUGGAGGAG 20 9747

SCNNlA-5899 + GGUGAGCAGGGCGGGGGGAG 20 9748

SCNNlA-5900 - GGGCAAGGCAAGGGGGGGAG 20 9749

SCNNlA-436 - GGUUCCAGGGGUGAUGGGAG 20 4285

SCNNlA-5901 - GCAGAUAGAGAGGGAGUGAG 20 9750

1342

5535.1 SCNNlA-5902 + GGGACAGGAUGGCAGGUGAG 20 9751

SCNNlA-5903 - GGAAGAAGACCAAAGGAAGG 20 9752

SCNNlA-5904 + GGUGAGCAAGGAGAGAGAGG 20 9753

SCNNlA-5905 - GAGGCAGGAUUAGAGAGAGG 20 9754

SCNNlA-5906 - GGCUCCAGGAAAGGUGGAGG 20 9755

SCNNlA-5907 + GGCGGGGGGAGGGGCUGAGG 20 9756

SCNNlA-5908 - GCUGCACCUGUCAGGUGAGG 20 9757

SCNNlA-5909 - GGGGGCAGAGACAGAAAGGG 20 9758

SCNNlA-5910 - GAGAGGGGGCAAGGCAAGGG 20 9759

SCNNlA-5911 - GAAAGGUGGAGGAGGGAGGG 20 9760

SCNNlA-5912 - GUCUGCUGGCUUGUGGAGGG 20 9761

SCNNlA-5913 - GCUCUGUGUGGGAGUGAGGG 20 9762

SCNNlA-5914 - GCACCUGUCAGGUGAGGGGG 20 9763

SCNNlA-5915 + GGACAGAGAGAUAGGGAUGG 20 9764

SCNNlA-5916 + GAGUGAGUAGAGGCAGGUGG 20 9765

SCNNlA-5917 - GAGGGAGGAGUGGGAGAAUG 20 9766

SCNNlA-5918 + GAGGGGCCCAGGUGAAGCUG 20 9767

SCNNlA-5919 + GCAGACAGGCAAGGAGGCUG 20 9768

SCNNlA-5920 + GGGGGACAGGAUGGCAGGUG 20 9769

SCNNlA-5921 + GCAGGUGGGGGGCAGUGGUG 20 9770

SCNNlA-5922 + GUCUGUGGCUUCCUCUCUUG 20 9771

SCNNlA-5923 + GGAGGGGCCCAGGUGAAGCU 20 9772

SCNNlA-5924 + GGGCCAAAAGUGCCGGAGCU 20 9773

SCNNlA-5925 - GAGACAGAAAGGGAGGUGCU 20 9774

SCNNlA-5926 - GCAGAGAUGACACCUUCUCU 20 9775

SCNNlA-5927 + GAGCUAGAGGCUCAGCAAGU 20 9776

SCNNlA-5928 + GGCAGGUGGGGGGCAGUGGU 20 9777

SCNNlA-5929 - GGUGAGGGGGAGGAGAGGUU 20 9778

SCNNlA-437 - GUAAGCAAGGGAACCUGGUU 20 4286

Table 46D provides exemplary targeting domains for knocking down the SCNNIA gene selected according to the fourth tier parameters. The targeting domains bind within 500 bp (e.g., upstream or downstream) of a transcription start site (TSS). It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. pyogenes eiCas9 molecule or eiCas9 fusion protein (e.g., an eiCas9 fused to a transcription repressor domain) to alter the SCNNIA gene (e.g., reduce or eliminate SCNNIA gene expression, SCNNIA protein function, or the level of SCNNIA protein). One or more gRNA may be used to target an eiCas9 to the promoter region of the SCNNIA gene

1343

5535.1 Table 46D

1344

5535.1 SCNNlA-5961 + CAAGGAGGCUGGGGGAC 17 9810

SCNNlA-5962 + AACCAGGAUUCCAAACC 17 9811

SCNNlA-445 - AGGUAAGCAAGGGAACC 17 4294

SCNNlA-5963 + CGGGGCUCAGGUGCACC 17 9812

SCNNlA-5964 - UAGCCCCCAGCUUCACC 17 9813

SCNNlA-5965 + CACUGUGGACACAGACC 17 9814

SCNNlA-5966 - AGAGGAAGCCACAGACC 17 9815

SCNNlA-5967 - AGGAAAGAGGAGGGACC 17 9816

SCNNlA-5968 + AGCCACCCACACAACCC 17 9817

SCNNlA-446 + CCCUCUCCCAUCACCCC 17 4295

SCNNlA-151 + UUCCCCUUCAUGAGCCC 17 648

SCNNlA-5969 + CACGCCUAGACAGGCCC 17 9818

SCNNlA-5970 + UCCAGCUUCCCACUCCC 17 9819

SCNNlA-5971 - UCACCUGGGCCCCUCCC 17 9820

SCNNlA-5972 + ACCUGGAUGUGAAAGCC 17 9821

SCNNlA-5973 - UUUGAGAUCAAACAGCC 17 9822

SCNNlA-5974 + AGGAGAAGGGGCCAGCC 17 9823

SCNNlA-5975 - CCCAGGCCCUCUCAGCC 17 9824

SCNNlA-5976 + CUGUUGGCUGCCAGGCC 17 9825

SCNNlA-5977 - AUUACACAUUCCUGGCC 17 9826

SCNNlA-5978 - AACCUGGUUUGGAAUCC 17 9827

SCNNlA-5979 - AGGCAGCCCAGACCUCC 17 9828

SCNNlA-5980 - CUGCCCUCCUGUCCUCC 17 9829

SCNNlA-5981 + CAGGACUGCAGGGCUCC 17 9830

SCNNlA-5982 - CUGGAGCCCUGCAGUCC 17 9831

SCNNlA-5983 - AGUGAGGGAGGCCUUCC 17 9832

SCNNlA-5984 - CCCCUUGCUCUCCUUCC 17 9833

SCNNlA-5985 - CUUUCCCUGCCUCUUCC 17 9834

SCNNlA-5986 + CCCUCCUCCACCUUUCC 17 9835

SCNNlA-5987 - ACCUGGGAGUGGGAAGC 17 9836

SCNNlA-5988 + UGAGGAGGAGUCAGAGC 17 9837

SCNNlA-5989 - AGGUCAGGGCCAGAGGC 17 9838

SCNNlA-5990 + CAGACAGGCAAGGAGGC 17 9839

SCNNlA-5991 + CUGGGGGACAGGAUGGC 17 9840

SCNNlA-5992 + CUCUGCCCCAGGACUGC 17 9841

SCNNlA-5993 - UCUUCUCUCUUCUCUGC 17 9842

SCNNlA-5994 - ACCACAUUCCUGCACUC 17 9843

SCNNlA-5995 + AGGGCUGGAGGAGACUC 17 9844

SCNNlA-5996 + CCCUCAGCUCCAGCCUC 17 9845

SCNNlA-5997 - UGCCUCUUCCUGGGCUC 17 9846

SCNNlA-5998 + CAGGGCUCCAGGAGGUC 17 9847

SCNNlA-5999 - UGGGCCCCUCCCGGGUC 17 9848

1345

5535.1 SCNNlA-6000 + UCCUGCUCUCCUCUUUC 17 9849

SCNNlA-6001 - AG G A A U C AG C AG G A A AG 17 9850

SCNNlA-6002 + CCAGGAAGGAGAGCAAG 17 9851

SCNNlA-6003 - AGAGGGGGCAAGGCAAG 17 9852

SCNNlA-6004 + UGCAGAGAAGAGAGAAG 17 9853

SCNNlA-6005 - AAGAAGACCAAAGGAAG 17 9854

SCNNlA-6006 + AGGCAGGUGGGGGGCAG 17 9855

SCNNlA-6007 + AGAGGGAGACAAUAGAG 17 9856

SCNNlA-6008 - ACAGAAGGCAGAUAGAG 17 9857

SCNNlA-6009 + AGCAAAAGGAUAAGGAG 17 9858

SCNNlA-6010 - UCAGGGAAGCAGAGGAG 17 9859

SCNNlA-6011 - CAGGUGAGGGGGAGGAG 17 9860

SCNNlA-6012 + AGAUAGGGAUGGAGGAG 17 9861

SCNNlA-448 - UCCAGGGGUGAUGGGAG 17 4297

SCNNlA-83 - UACCAGGUCUCAUGGAG 17 606

SCNNlA-6013 + ACAGGAUGGCAGGUGAG 17 9862

SCNNlA-6014 - UGCACCUGUCAGGUGAG 17 9863

SCNNlA-6015 + AAGCUGGGGGCUAGGCG 17 9864

SCNNlA-6016 + CAGGAAGGAGAGCAAGG 17 9865

SCNNlA-6017 + UACUGGACCUGAGAAGG 17 9866

SCNNlA-6018 - AGAAGACCAAAGGAAGG 17 9867

SCNNlA-6019 - AAAGAGGAGGGACCAGG 17 9868

SCNNlA-6020 - A A U C AG C AG G A A AG AG G 17 9869

SCNNlA-6021 + AGACAGGCCCUGGGAGG 17 9870

SCNNlA-6022 + AGAGAUAGGGAUGGAGG 17 9871

SCNNlA-6023 - UCCAGGAAAG G U G G AG G 17 9872

SCNNlA-6024 - CUGGACAAGGUUGGAGG 17 9873

SCNNlA-6025 + CUGAGCCCACAGCUAGG 17 9874

SCNNlA-6026 + UGAAGCUGGGGGCUAGG 17 9875

SCNNlA-6027 + AGGAAGGAGAGCAAGGG 17 9876

SCNNlA-6028 - AGGGGGCAAGGCAAGGG 17 9877

SCNNlA-6029 - AAA U AG A A A AG G C AG G G 17 9878

SCNNlA-6030 - AGGUGGAGGAGGGAGGG 17 9879

SCNNlA-6031 - UGCUGGCUUGUGGAGGG 17 9880

SCNNlA-6032 - CUGUGUGGGAGUGAGGG 17 9881

SCNNlA-6033 - CCUGUCAGGUGAGGGGG 17 9882

SCNNlA-6034 + CAGAGAGAUAGGGAUGG 17 9883

SCNNlA-6035 - UGGGAGUGGGAAGCUGG 17 9884

SCNNlA-6036 + ACAGGCAAGGAGGCUGG 17 9885

SCNNlA-6037 + CAGGUGGGGGGCAGUGG 17 9886

SCNNlA-6038 + UGAGUAGAGGCAGGUGG 17 9887

SCNNlA-154 + CCUGGAGUGGACUGUGG 17 651

1346

5535.1 SCNNlA-6039 + CCCAGAGUGCAGGAAUG 17 9888

SCNNlA-6040 + AAGGUGCAGGGAGGAUG 17 9889

SCNNlA-153 + AGCCCUGGAGUGGACUG 17 650

SCNNlA-6041 + UGGAGCCAGCAGACCUG 17 9890

SCNNlA-6042 - AGGGUGAGGCUGACCUG 17 9891

SCNNlA-6043 - CUUCUCUGCAGGGCCUG 17 9892

SCNNlA-6044 - CUCUGGGCUGCCUCCUG 17 9893

SCNNlA-6045 + AUUCUCCUCCUCCUCUG 17 9894

SCNNlA-6046 - UGCAGGGCCUGAGGGUG 17 9895

SCNNlA-6047 + CUGAGAGGGCCUGGGUG 17 9896

SCNNlA-6048 - CUGGGCUGCCUCCUGUG 17 9897

SCNNlA-6049 - CUUUGUCUGCUGGCUUG 17 9898

SCNNlA-6050 + UUCCCACUCCCAGGUUG 17 9899

SCNNlA-6051 + AG G U U AG A A A AC A A A A U 17 9900

SCNNlA-449 - CCAGGGGCAGCCUCACU 17 4298

SCNNlA-6052 + AAGGGCUGGAGGAGACU 17 9901

SCNNlA-6053 - UCCUGCAGUGAGCCCCU 17 9902

SCNNlA-450 + CUCAUGAUACCUCCCCU 17 4299

SCNNlA-6054 - CCCAGUUCACCUGCCCU 17 9903

SCNNlA-6055 + CCAGGCUGAGAGGGCCU 17 9904

SCNNlA-6056 - UGGAGCCCUGCAGUCCU 17 9905

SCNNlA-6057 - A A AG A AC AG A A U G U C C U 17 9906

SCNNlA-6058 - UUUCCCUGCCUCUUCCU 17 9907

SCNNlA-6059 + AGACAGGCAAGGAGGCU 17 9908

SCNNlA-6060 + AGGUGAAGCUGGGGGCU 17 9909

SCNNlA-6061 - ACAGAAAGGGAGGUGCU 17 9910

SCNNlA-6062 + UCUGCUCUCUGGGUGCU 17 9911

SCNNlA-6063 + AAUUCUCCUCCUCCUCU 17 9912

SCNNlA-6064 - CCUCCCAGGGCCUGUCU 17 9913

SCNNlA-6065 - AGGAGGGAGGGAGGAGU 17 9914

SCNNlA-6066 + CUGGAAAGGAAGAGGGU 17 9915

SCNNlA-6067 + AGGUGGGGGGCAGUGGU 17 9916

SCNNlA-6068 - CAGGGCCUGGGUUGUGU 17 9917

SCNNlA-6069 - AAAACUGAUUUAUCCUU 17 9918

SCNNlA-6070 + UCUCUGCCCCCUUCCUU 17 9919

SCNNlA-6071 + UGCCUUCUGUUUCUCUU 17 9920

SCNNlA-6072 - AGUUUGGAAAGAGAUUU 17 9921

SCNNlA-6073 + CAGAGAAUCAGACCCAAAAA 20 9922

SCNNlA-6074 + UUAAAAGAUUGUCUUUAAAA 20 9923

SCNNlA-6075 + UCCAAACUUAAUGCAGCAAA 20 9924

SCNNlA-6076 + UAGCAGGCAAAGAAGAGAAA 20 9925

SCNNlA-6077 - AGUCUGUCUCAGGAAGUAAA 20 9926

1347

5535.1 SCNNlA-6078 + CUCCACAAGCCAGCAGACAA 20 9927

SCNNlA-6079 - AGUGAGAGGGGGCAAGGCAA 20 9928

SCNNlA-451 - UCCACUCCGGGGCUCAUGAA 20 4300

SCNNlA-6080 - ACGAAUUUCUCCUCCUCCCA 20 9929

SCNNlA-6081 + ACCACUAGCUUAAGGCAGCA 20 9930

SCNNlA-452 - CGCAGGGUGGGACAUGGGCA 20 4301

SCNNlA-6082 - CCUCUUCUCUCUUCUCUGCA 20 9931

SCNNlA-6083 + UACUUCCUGAGACAGACUCA 20 9932

SCNNlA-6084 - CAGGACACAGCUCGAGGUCA 20 9933

SCNNlA-6085 + AGGACAGGAGGGCAGAAAGA 20 9934

SCNNlA-6086 + UCAGGAAGCCUUCCCAGAGA 20 9935

SCNNlA-6087 + AAAGAGGGAGACAAUAGAGA 20 9936

SCNNlA-6088 - AAACAGAAGGCAGAUAGAGA 20 9937

SCNNlA-6089 + AGGAGGGCAACACAAGGAGA 20 9938

SCNNlA-6090 + AGGGGCCAGCCAGGCUGAGA 20 9939

SCNNlA-6091 + CAGUGGUGGGGGCAAAUAGA 20 9940

SCNNlA-6092 + CAAAGAUCUGAACAAGUAGA 20 9941

SCNNlA-6093 + AAGGAGGCUGGGGGACAGGA 20 9942

SCNNlA-6094 + AGAGAGAUAGGGAUGGAGGA 20 9943

SCNNlA-6095 - CAGGAAAGGUGGAGGAGGGA 20 9944

SCNNlA-6096 + AGGUGAGCAGGGCGGGGGGA 20 9945

SCNNlA-6097 + CAGCGAAGGACAGAGAGAUA 20 9946

SCNNlA-6098 + CUUAAUGCAGCAAAAGGAUA 20 9947

SCNNlA-6099 + CCAAGGGCUAGGGGAGCCUA 20 9948

SCNNlA-6100 - A A A A AG A AC AG A A U G U C C U A 20 9949

SCNNlA-6101 + AGAGGGCCUGGGUGGGGAAC 20 9950

SCNNlA-6102 + AGGCAAGGAGGCUGGGGGAC 20 9951

SCNNlA-6103 + UCUCCUCCCCCUCACCUGAC 20 9952

SCNNlA-6104 - AAGAGAGGAAGCCACAGACC 20 9953

SCNNlA-77 + UUGUUCCCCUCCAUGAGACC 20 603

SCNNlA-6105 + CAAUAAGGUGCUCAGCACCC 20 9954

SCNNlA-72 + UUGUUCCCCUUCAUGAGCCC 20 599

SCNNlA-6106 + UCCAGACCCGGGAGGGGCCC 20 9955

SCNNlA-6107 + UGCACCUGGAUGUGAAAGCC 20 9956

SCNNlA-6108 - CCACCCAGGCCCUCUCAGCC 20 9957

SCNNlA-6109 + AGCCCGCCCGCUGGCCGGCC 20 9958

SCNNlA-6110 + CCAGCCAGGCUGAGAGGGCC 20 9959

SCNNlA-6111 + UCCUUUGGUCUUCUUCCUCC 20 9960

SCNNlA-6112 + CCCCAGGACUGCAGGGCUCC 20 9961

SCNNlA-6113 - CCUGCCUCUUCCUGGGCUCC 20 9962

SCNNlA-6114 - CUCCUGGAGCCCUGCAGUCC 20 9963

SCNNlA-6115 - CUGCUUUCCCUGCCUCUUCC 20 9964

1348

5535.1 SCNNlA-6116 + CCUCCCUCCUCCACCUUUCC 20 9965

SCNNlA-6117 + CAGGAAGAGGCAGGGAAAGC 20 9966

SCNNlA-6118 + CGACUUCUUAAAGUGAAAGC 20 9967

SCNNlA-6119 - CAGGCCAGAAAGAGGAGAGC 20 9968

SCNNlA-6120 + AGGGAGGAUGUGGCCAGCGC 20 9969

SCNNlA-6121 - AG C U G G C A A A U AG A A A AG G C 20 9970

SCNNlA-6122 + CCCGGAGCCCAGGAAGAGGC 20 9971

SCNNlA-6123 - AUAGAGAGGGAGUGAGAGGC 20 9972

SCNNlA-6124 - CAGGAUUAGAGAGAGGAGGC 20 9973

SCNNlA-6125 + AGGCUGGGGGACAGGAUGGC 20 9974

SCNNlA-6126 - CCAGGCCCUCUCAGCCUGGC 20 9975

SCNNlA-6127 + UGGGGAGCCCGCCCGCUGGC 20 9976

SCNNlA-6128 + UGUCUCUGCCCCAGGACUGC 20 9977

SCNNlA-6129 - ACCUCUUCUCUCUUCUCUGC 20 9978

SCNNlA-6130 + CAGGAGGCAGCCCAGAGUGC 20 9979

SCNNlA-6131 - AGACAGACUCCCUUUGGUGC 20 9980

SCNNlA-6132 - CUCCCAGUUCACCUGCCCUC 20 9981

SCNNlA-6133 + AGGCCCUCAGCUCCAGCCUC 20 9982

SCNNlA-6134 + UCAGAAUUCUCCUCCUCCUC 20 9983

SCNNlA-6135 - CCCUGCCUCUUCCUGGGCUC 20 9984

SCNNlA-6136 + CUGCAGGGCUCCAGGAGGUC 20 9985

SCNNlA-6137 - ACCUGGGCCCCUCCCGGGUC 20 9986

SCNNlA-6138 + CUCUCCUGCUCUCCUCUUUC 20 9987

SCNNlA-6139 - AGAGGAGGCAGGCCAGAAAG 20 9988

SCNNlA-6140 + UCUCCAGGAAGGAGAGCAAG 20 9989

SCNNlA-6141 + CCCUGCAGAGAAGAGAGAAG 20 9990

SCNNlA-6142 - AGGAAGAAGACCAAAGGAAG 20 9991

SCNNlA-453 - CCACUCCGGGGCUCAUGAAG 20 4302

SCNNlA-6143 + UAGAGGCAGGUGGGGGGCAG 20 9992

SCNNlA-6144 + CCCUCACCUGACAGGUGCAG 20 9993

SCNNlA-6145 - CAAGGGGGGGAGAGGAAGAG 20 9994

SCNNlA-6146 + AGUGGUGAGCAAGGAGAGAG 20 9995

SCNNlA-6147 - AGAGAGGCAGGAUUAGAGAG 20 9996

SCNNlA-6148 - CUAUCAGGGAAGCAGAGGAG 20 9997

SCNNlA-6149 - UGUCAGGUGAGGGGGAGGAG 20 9998

SCNNlA-454 + CCCCUUCAUGAGCCCCGGAG 20 4303

SCNNlA-6150 - UCUGCUGGCUCCAGGAAAGG 20 9999

SCNNlA-6151 + CUCCAGGAAGGAGAGCAAGG 20 10000

SCNNlA-6152 - UGAGAGGGGGCAAGGCAAGG 20 10001

SCNNlA-6153 - AGGAAAGAGGAGGGACCAGG 20 10002

SCNNlA-6154 + CAGGACUGCAGGGCUCCAGG 20 10003

SCNNlA-6155 - AGGAAUCAGCAGGAAAGAGG 20 10004

1349

5535.1 SCNNlA-6156 - AAAGAGGAGGGACCAGGAGG 20 10005

SCNNlA-6157 + CCUAGACAGGCCCUGGGAGG 20 10006

SCNNlA-6158 + CAGAGAGAUAGGGAUGGAGG 20 10007

SCNNlA-6159 + UCCAGGAAGGAGAGCAAGGG 20 10008

SCNNlA-6160 + UCAAUUAAAGGUGAGCAGGG 20 10009

SCNNlA-6161 + AGCGCUGGAAAGGAAGAGGG 20 10010

SCNNlA-6162 - CCAGGAAAGGUGGAGGAGGG 20 10011

SCNNlA-6163 - AGAGGGGGCAAGGCAAGGGG 20 10012

SCNNlA-6164 + AAGGUGAGCAGGGCGGGGGG 20 10013

SCNNlA-6165 + CCAGGCUGAGAGGGCCUGGG 20 10014

SCNNlA-6166 + AGUGAGUAGAGGCAGGUGGG 20 10015

SCNNlA-6167 - CAGGGCCUGGGUUGUGUGGG 20 10016

SCNNlA-455 - CAUGAAGGGGAACAAGCUGG 20 4304

SCNNlA-6 - CAUGGAGGGGAACAAGCUGG 20 558

SCNNlA-6168 - ACCUGGGAGUGGGAAGCUGG 20 10017

SCNNlA-6169 + AGGGGCCCAGGUGAAGCUGG 20 10018

SCNNlA-6170 + CAGACAGGCAAGGAGGCUGG 20 10019

SCNNlA-6171 + AGGCAGGUGGGGGGCAGUGG 20 10020

SCNNlA-6172 + CAGGUGGGGGGCAGUGGUGG 20 10021

SCNNlA-6173 + CAGCCCAGAGUGCAGGAAUG 20 10022

SCNNlA-6174 - CCUGGAGCCCUGCAGUCCUG 20 10023

SCNNlA-6175 - AGGGCCAGAGGCUGGAGCUG 20 10024

SCNNlA-6176 + CAGGGCGGGGGGAGGGGCUG 20 10025

SCNNlA-6177 + AGGCUGAGAGGGCCUGGGUG 20 10026

SCNNlA-6178 + AGCUUCCCACUCCCAGGUUG 20 10027

SCNNlA-6179 + ACUUCCUGAGACAGACUCAU 20 10028

SCNNlA-456 - UGGCCAGGGGCAGCCUCACU 20 4305

SCNNlA-457 + CUGCUCAUGAUACCUCCCCU 20 4306

SCNNlA-6180 + CAGCCAGGCUGAGAGGGCCU 20 10029

SCNNlA-6181 - UCAGAAAACUGAUUUAUCCU 20 10030

SCNNlA-6182 - AAAAAAGAACAGAAUGUCCU 20 10031

SCNNlA-6183 - UGCUUUCCCUGCCUCUUCCU 20 10032

SCNNlA-6184 + CCCAGGUGAAGCUGGGGGCU 20 10033

SCNNlA-6185 + CAGAAUUCUCCUCCUCCUCU 20 10034

SCNNlA-6186 - CCUCCUCCCAGGGCCUGUCU 20 10035

SCNNlA-6187 - UGGAGGAGGGAGGGAGGAGU 20 10036

SCNNlA-6188 + CAGGCUGAGAGGGCCUGGGU 20 10037

SCNNlA-6189 - CAGAAAACUGAUUUAUCCUU 20 10038

SCNNlA-6190 + CUGUCUCUGCCCCCUUCCUU 20 10039

SCNNlA-6191 + AUCUGCCUUCUGUUUCUCUU 20 10040

SCNNlA-6192 + UCUGCCUUCUGUUUCUCUUU 20 10041

1350

5535.1 Table 46E provides exemplary targeting domains for knocking down the SCNNIA gene selected according to the fifth tier parameters. The targeting domains bind within the additional 500 bp (e.g., upstream or downstream) of a transcription start site (TSS), e.g., extending to lkb upstream and downstream of a TSS. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. pyogenes eiCas9 molecule or eiCas9 fusion protein (e.g., an eiCas9 fused to a transcription repressor domain) to alter the SCNNIA gene (e.g., reduce or eliminate SCNNIA gene expression, SCNNIA protein function, or the level of SCNNIA protein). One or more gRNA may be used to target an eiCas9 to the promoter region of the SCNNIA gene.

Table 46E

1351

5535.1 SCNNlA-106 - GCACAACCGCAUGAAGA 17 540

SCNNlA-126 + CCACAGCACUGCCCAGA 17 633

SCNNlA-442 + ACCAGGGAAGGGGCAGA 17 4291

SCNNlA-115 + GGGAUUGAGGGUGCAGA 17 542

SCNNlA-6210 - UUUGGGGAGGGAAAGGA 17 10059

SCNNlA-132 + GGAGCACACCAGGCGGA 17 547

SCNNlA-6211 + GGCGCAGGCACCAGGGA 17 10060

SCNNlA-6212 - UGGCUCCCCUUUGGGGA 17 10061

SCNNlA-6213 - UGGUGCCUGCGCCUGGA 17 10062

SCNNlA-134 + GCGGAUGGCGCCGUGGA 17 548

SCNNlA-155 + CUGGAGUGGACUGUGGA 17 652

SCNNlA-89 - CACUCCAGGGCUCAUGA 17 610

SCNNlA-6214 - CAGAGCCUCAGACCUGA 17 10063

SCNNlA-121 + GUUGAUGUUGAGGCUGA 17 545

SCNNlA-367 + CGACCUGUAGGGAUUGA 17 4216

SCNNlA-6215 - GGAAAGGAAGGGGACUA 17 10064

SCNNlA-6216 + CCACGUCCUGCCGGGUA 17 10065

SCNNlA-331 + GGACUAACCGACCUGUA 17 4180

SCNNlA-6217 - G ACAG AU AU ACAAAU U A 17 10066

SCNNlA-6218 + CUGGAGCGGGCUAGAAC 17 10067

SCNNlA-6219 - GGUGCUGAGGUGCUCAC 17 10068

SCNNlA-6220 + UUAUUUAUCUUAGAGAC 17 10069

SCNNlA-6221 + UGAGCUCUACCUGGGAC 17 10070

SCNNlA-122 + UUGAUGUUGAGGCUGAC 17 629

SCNNlA-332 - GCACCCUCAAUCCCUAC 17 4181

SCNNlA-111 - CCUUUGGCAUGAUGUAC 17 622

SCNNlA-130 + UGUGCUGGGAGCACACC 17 637

SCNNlA-6222 + UUCCAGGCGCAGGCACC 17 10071

SCNNlA-6223 - UUGGCUCAGCCCAGACC 17 10072

SCNNlA-6224 + AAUAGAAAUCUGAGACC 17 10073

SCNNlA-6225 + CUGCAGCAUUCUAGACC 17 10074

SCNNlA-6226 - AUUGCCACUCCCAUACC 17 10075

SCNNlA-6227 + CAGCAGUGAGCUCUACC 17 10076

SCNNlA-6228 + UGAGCACCUCAGCACCC 17 10077

SCNNlA-151 + UUCCCCUUCAUGAGCCC 17 648

SCNNlA-6229 - ACUGACACCCCUGUCCC 17 10078

SCNNlA-447 - UCCCUCUGCCCCUUCCC 17 4296

SCNNlA-105 - CCACGGCGCCAUCCGCC 17 618

SCNNlA-6230 - UCCCUGGUGCCUGCGCC 17 10079

SCNNlA-5364 + AGAAGAAUUGCAAUGCC 17 9213

SCNNlA-6231 + CCCUGCCACGUCCUGCC 17 10080

SCNNlA-87 - CCUCCACAGUCCACUCC 17 608

1352

5535.1 SCNNlA-6232 - CUGUUCUAGCCCGCUCC 17 10081

SCNNlA-6233 - ACUUCUGACCAAAGUCC 17 10082

SCNNlA-6234 - GCCUGGAAGGGUGGUCC 17 10083

SCNNlA-6235 + CCCUGGACCACCCUUCC 17 10084

SCNNlA-124 + AGUACUCUCCGAAAAGC 17 631

SCNNlA-93 - GAACAAG CG U G AG G AG C 17 533

SCNNlA-6236 + CAUUCUAGACCUGGAGC 17 10085

SCNNlA-147 + GGCUGCUGGGGCGCCGC 17 554

SCNNlA-6237 + ACCACCCUUCCAGGCGC 17 10086

SCNNlA-6238 + UGCACUAUCCUCUAGGC 17 10087

SCNNlA-6239 - CCACUCCCAUACCCGGC 17 10088

SCNNlA-96 - GCGUGAGGAGCAGGGGC 17 534

SCNNlA-6240 - UGAGGUGCUCACUGGGC 17 10089

SCNNlA-6241 - ACCCGGCAGGACGUGGC 17 10090

SCNNlA-6242 - CAGGUAGAGCUCACUGC 17 10091

SCNNlA-117 + GUGCAGAUGGUCACUGC 17 544

SCNNlA-6243 + ACCCUGCCACGUCCUGC 17 10092

SCNNlA-144 + CCUCCGCCGUGGGCUGC 17 643

SCNNlA-128 + UCUUCAUGCGGUUGUGC 17 635

SCNNlA-140 + AGCGGUGGAACUCGAUC 17 642

SCNNlA-6244 + UGUCAGUUCCCACCCUC 17 10093

SCNNlA-5415 + AAUUGCAAUGCCUGGUC 17 9264

SCNNlA-107 - GCAUGAAGACGGCCUUC 17 541

SCNNlA-149 + UGGGGCGCCGCAGGUUC 17 647

SCNNlA-6245 + CCUUUCCCUCCCCAAAG 17 10094

SCNNlA-6246 - UGGGGAGGGAAAGGAAG 17 10095

SCNNlA-6247 + CGCAGGCACCAGGGAAG 17 10096

SCNNlA-91 - CUCCAGGGCUCAUGAAG 17 612

SCNNlA-6248 + AGCUCUACCUGGGACAG 17 10097

SCNNlA-95 - ACAAGCGUGAGGAGCAG 17 614

SCNNlA-6249 + C AC C AG G G A AG G G G C AG 17 10098

SCNNlA-138 + AGAGCUCUCGGUAGGAG 17 641

SCNNlA-6250 + CCUGCCGGGUAUGGGAG 17 10099

SCNNlA-6251 + GCAUUCUAGACCUGGAG 17 10100

SCNNlA-152 + CUUCAUGAGCCCUGGAG 17 649

SCNNlA-6252 - GCUGUACUCCAGCCUAG 17 10101

SCNNlA-6253 - CCAUACCCGGCAGGACG 17 10102

SCNNlA-123 + UGAUGUUGAGGCUGACG 17 630

SCNNlA-142 + GGCCUCCUCCUCCGCCG 17 552

SCNNlA-133 + CCAGGCGGAUGGCGCCG 17 638

SCNNlA-118 + UGCAGAUGGUCACUGCG 17 626

SCNNlA-150 + GGGGCGCCGCAGGUUCG 17 555

1353

5535.1 SCNNlA-131 + GCUGGGAGCACACCAGG 17 546

SCNNlA-103 - GCCCACGGCGGAGGAGG 17 539

SCNNlA-102 - GCAGCCCACGGCGGAGG 17 538

SCNNlA-100 - GCCCCAGCAGCCCACGG 17 537

SCNNlA-139 + GCUCUCGGUAGGAGCGG 17 550

SCNNlA-101 - CCAGCAGCCCACGGCGG 17 616

SCNNlA-6254 + UGGGCUGAGCCAAAGGG 17 10103

SCNNlA-6255 - GCCUGCGCCUGGAAGGG 17 10104

SCNNlA-6256 - AGCCUCAGACCUGAGGG 17 10105

SCNNlA-6257 - GUGGCUCCCCUUUGGGG 17 10106

SCNNlA-135 + GAUGGCGCCGUGGAUGG 17 549

SCNNlA-6258 - AGAUAUACAAAUUAUGG 17 10107

SCNNlA-154 + CCUGGAGUGGACUGUGG 17 651

SCNNlA-127 + AGAAGGCCGUCUUCAUG 17 634

SCNNlA-116 + GGUGCAGAUGGUCACUG 17 543

SCNNlA-153 + AGCCCUGGAGUGGACUG 17 650

SCNNlA-98 - GCUGGGCCCCGAACCUG 17 535

SCNNlA-6259 - GCAGAGCCUCAGACCUG 17 10108

SCNNlA-146 + UCCGCCGUGGGCUGCUG 17 645

SCNNlA-109 - CCUUCUGGGCAGUGCUG 17 620

SCNNlA-6260 - GGUGGUCCAGGGUGCUG 17 10109

SCNNlA-6261 + UCCCACCCUCAGGUCUG 17 10110

SCNNlA-92 - GAAGGGGAACAAGCGUG 17 532

SCNNlA-6262 + ACAGGCUUGGUGUUGUG 17 10111

SCNNlA-386 + CCGACCUGUAGGGAUUG 17 4235

SCNNlA-119 + CGAGCUUGUCCGAGUUG 17 627

SCNNlA-120 + AGUUGAGGUUGAUGUUG 17 628

SCNNlA-6263 - AUGGUGGCUCCCCUUUG 17 10112

SCNNlA-6264 + GACAGAGACCAUGCUAU 17 10113

SCNNlA-6265 + CACGUCCUGCCGGGUAU 17 10114

SCNNlA-114 - CAACAUCAACCUCAACU 17 625

SCNNlA-6266 - UAGAAUGCUGCAGCACU 17 10115

SCNNlA-6267 - GUGCUGAGGUGCUCACU 17 10116

SCNNlA-6268 + AGCAGUGAGCUCUACCU 17 10117

SCNNlA-6269 + GCGGGCUAGAACAGGCU 17 10118

SCNNlA-97 - CGUGAGGAGCAGGGGCU 17 615

SCNNlA-145 + CUCCGCCGUGGGCUGCU 17 644

SCNNlA-129 + CUUCAUGCGGUUGUGCU 17 636

SCNNlA-6270 + AUCAUGCACUAUCCUCU 17 10119

SCNNlA-136 + AGAACUCGAAGAGCUCU 17 639

SCNNlA-6271 + AUUGCAAUGCCUGGUCU 17 10120

SCNNlA-108 - CAUGAAGACGGCCUUCU 17 619

1354

5535.1 SCNNlA-143 + GCCUCCUCCUCCGCCGU 17 553

SCNNlA-391 - CCUCAAUCCCUACAGGU 17 4240

SCNNlA-137 + CUCGAAGAGCUCUCGGU 17 640

SCNNlA-6272 - GCCUCAGACCUGAGGGU 17 10121

SCNNlA-338 + GGGACUAACCGACCUGU 17 4187

SCNNlA-112 - AUGAUGUACUGGCAAUU 17 623

SCNNlA-6273 + AUCUGAGACCUGGACUU 17 10122

SCNNlA-110 - CUGUGGCUCUGCACCUU 17 621

SCNNlA-6274 - GCAGGGUCACCACCCUU 17 10123

SCNNlA-6275 - UUAUGGUGGCUCCCCUU 17 10124

SCNNlA-148 + CUGGGGCGCCGCAGGUU 17 646

SCNNlA-6276 - UAUGGUGGCUCCCCUUU 17 10125

SCNNlA-113 - CAAUUCGGCCUGCUUUU 17 624

SCNNlA-6277 - U A AG A A A A U A A A AG C A A A A A 20 10126

SCNNlA-6278 - UUAAAAGAUCAUCUUUAAAA 20 10127

SCNNlA-6279 + CCUUCCUUUCCCUCCCCAAA 20 10128

SCNNlA-6280 + CUGGUCUGGGCUGAGCCAAA 20 10129

SCNNlA-6281 + CCCUUCCUUUCCCUCCCCAA 20 10130

SCNNlA-6282 + CCUGGUCUGGGCUGAGCCAA 20 10131

SCNNlA-46 + UUGCCAGUACAUCAUGCCAA 20 580

SCNNlA-6283 - CCUUUGGGGAGGGAAAGGAA 20 10132

SCNNlA-6284 + CAGGCGCAGGCACCAGGGAA 20 10133

SCNNlA-6285 - GCUCCCCUUUGGGGAGGGAA 20 10134

SCNNlA-6286 - CCUGGUGCCUGCGCCUGGAA 20 10135

SCNNlA-11 - UCCACUCCAGGGCUCAUGAA 20 560

SCNNlA-6287 - AAAUACAUGUAAGUUUAUAA 20 10136

SCNNlA-6288 - AGGGAAAGGAAGGGGACUAA 20 10137

SCNNlA-6289 + AGUGAGCUCUACCUGGGACA 20 10138

SCNNlA-6290 + CCUUCCAGGCGCAGGCACCA 20 10139

SCNNlA-20 - UGCGGCGCCCCAGCAGCCCA 20 565

SCNNlA-25 - UGCAACAACACCACCAUCCA 20 567

SCNNlA-9 - GCCCUCCACAGUCCACUCCA 20 499

SCNNlA-6291 - GCGCCUGGAAGGGUGGUCCA 20 10140

SCNNlA-15 - GGGAACAAGCGUGAGGAGCA 20 507

SCNNlA-6292 - GUAGAAACAUACCUAUAGCA 20 10141

SCNNlA-6293 - AUACCCGGCAGGACGUGGCA 20 10142

SCNNlA-62 + GGAGCGGUGGAACUCGAUCA 20 525

SCNNlA-27 - CCAGCACAACCGCAUGAAGA 20 569

SCNNlA-47 + GAGCCACAGCACUGCCCAGA 20 521

SCNNlA-6294 + GGCACCAGGGAAGGGGCAGA 20 10143

SCNNlA-36 + GUAGGGAUUGAGGGUGCAGA 20 516

SCNNlA-6295 - CCCUUUGGGGAGGGAAAGGA 20 10144

1355

5535.1 SCNNlA-53 + CUGGGAGCACACCAGGCGGA 20 585

SCNNlA-6296 + CCAGGCGCAGGCACCAGGGA 20 10145

SCNNlA-6297 - UGGUGGCUCCCCUUUGGGGA 20 10146

SCNNlA-6298 - CCCUGGUGCCUGCGCCUGGA 20 10147

SCNNlA-55 + CAGGCGGAUGGCGCCGUGGA 20 587

SCNNlA-76 + GCCCUGGAGUGGACUGUGGA 20 528

SCNNlA-10 - GUCCACUCCAGGGCUCAUGA 20 505

SCNNlA-6299 - AGGCAGAGCCUCAGACCUGA 20 10148

SCNNlA-42 + GAGGUUGAUGUUGAGGCUGA 20 519

SCNNlA-402 + AACCGACCUGUAGGGAUUGA 20 4251

SCNNlA-6300 - GAGGGAAAGGAAGGGGACUA 20 10149

SCNNlA-6301 + CUGCCACGUCCUGCCGGGUA 20 10150

SCNNlA-345 + GAGGGACUAACCGACCUGUA 20 4194

SCNNlA-6302 - AU AG ACAG AU AU ACAAAU U A 20 10151

SCNNlA-6303 + GACCUGGAGCGGGCUAGAAC 20 10152

SCNNlA-6304 - CAGGGUGCUGAGGUGCUCAC 20 10153

SCNNlA-6305 + UUCUUAUUUAUCUUAGAGAC 20 10154

SCNNlA-6306 + CAGUGAGCUCUACCUGGGAC 20 10155

SCNNlA-43 + AGGUUGAUGUUGAGGCUGAC 20 578

SCNNlA-403 - UCUGCACCCUCAAUCCCUAC 20 4252

SCNNlA-32 - GCACCUUUGGCAUGAUGUAC 20 514

SCNNlA-51 + GGUUGUGCUGGGAGCACACC 20 522

SCNNlA-6307 + CCCUUCCAGGCGCAGGCACC 20 10156

SCNNlA-6308 - CCUUUGGCUCAGCCCAGACC 20 10157

SCNNlA-6309 + GAAAAUAGAAAUCUGAGACC 20 10158

SCNNlA-6310 + GUGCUGCAGCAUUCUAGACC 20 10159

SCNNlA-6311 - CGCAUUGCCACUCCCAUACC 20 10160

SCNNlA-6312 + UGCCAGCAGUGAGCUCUACC 20 10161

SCNNlA-6313 + CAGUGAGCACCUCAGCACCC 20 10162

SCNNlA-72 + UUGUUCCCCUUCAUGAGCCC 20 599

SCNNlA-6314 - GGAACUGACACCCCUGUCCC 20 10163

SCNNlA-407 - UAGUCCCUCUGCCCCUUCCC 20 4256

SCNNlA-26 - CAUCCACGGCGCCAUCCGCC 20 568

SCNNlA-6315 - CCUUCCCUGGUGCCUGCGCC 20 10164

SCNNlA-5223 + GUGAGAAGAAUUGCAAUGCC 20 9072

SCNNlA-6316 + UGACCCUGCCACGUCCUGCC 20 10165

SCNNlA-8 - AGCCCUCCACAGUCCACUCC 20 559

SCNNlA-6317 - AGCCUGUUCUAGCCCGCUCC 20 10166

SCNNlA-6318 - UGGACUUCUGACCAAAGUCC 20 10167

SCNNlA-6319 - UGCGCCUGGAAGGGUGGUCC 20 10168

SCNNlA-6320 + GCACCCUGGACCACCCUUCC 20 10169

SCNNlA-45 + UGAAGUACUCUCCGAAAAGC 20 579

1356

5535.1 SCNNlA-14 - GGGGAACAAGCGUGAGGAGC 20 506

SCNNlA-6321 + CAGCAUUCUAGACCUGGAGC 20 10170

SCNNlA-68 + GUGGGCUGCUGGGGCGCCGC 20 526

SCNNlA-6322 + UGGACCACCCUUCCAGGCGC 20 10171

SCNNlA-6323 + UCAUGCACUAUCCUCUAGGC 20 10172

SCNNlA-6324 - UUGCCACUCCCAUACCCGGC 20 10173

SCNNlA-17 - CAAGCGUGAGGAGCAGGGGC 20 563

SCNNlA-6325 - UGCUGAGGUGCUCACUGGGC 20 10174

SCNNlA-6326 - CAUACCCGGCAGGACGUGGC 20 10175

SCNNlA-6327 - UCCCAGGUAGAGCUCACUGC 20 10176

SCNNlA-38 + AGGGUGCAGAUGGUCACUGC 20 575

SCNNlA-6328 + GUGACCCUGCCACGUCCUGC 20 10177

SCNNlA-65 + CCUCCUCCGCCGUGGGCUGC 20 594

SCNNlA-49 + CCGUCUUCAUGCGGUUGUGC 20 582

SCNNlA-61 + AGGAGCGGUGGAACUCGAUC 20 591

SCNNlA-6329 + GGGUGUCAGUUCCCACCCUC 20 10178

SCNNlA-5640 + AAGAAUUGCAAUGCCUGGUC 20 9489

SCNNlA-28 - ACCGCAUGAAGACGGCCUUC 20 570

SCNNlA-70 + UGCUGGGGCGCCGCAGGUUC 20 598

SCNNlA-6330 + CUUCCUUUCCCUCCCCAAAG 20 10179

SCNNlA-6331 - CUUUGGGGAGGGAAAGGAAG 20 10180

SCNNlA-6332 + AGGCGCAGGCACCAGGGAAG 20 10181

SCNNlA-12 - CCACUCCAGGGCUCAUGAAG 20 561

SCNNlA-6333 + GUGAGCUCUACCUGGGACAG 20 10182

SCNNlA-16 - GGAACAAGCGUGAGGAGCAG 20 508

SCNNlA-6334 + AGGCACCAGGGAAGGGGCAG 20 10183

SCNNlA-59 + CGAAGAGCUCUCGGUAGGAG 20 589

SCNNlA-6335 + CGUCCUGCCGGGUAUGGGAG 20 10184

SCNNlA-6336 + GCAGCAUUCUAGACCUGGAG 20 10185

SCNNlA-73 + CCCCUUCAUGAGCCCUGGAG 20 600

SCNNlA-6337 - GCUGCUGUACUCCAGCCUAG 20 10186

SCNNlA-6338 - CUCCCAUACCCGGCAGGACG 20 10187

SCNNlA-44 + GGUUGAUGUUGAGGCUGACG 20 520

SCNNlA-63 + CAGGGCCUCCUCCUCCGCCG 20 592

SCNNlA-54 + ACACCAGGCGGAUGGCGCCG 20 586

SCNNlA-39 + GGGUGCAGAUGGUCACUGCG 20 518

SCNNlA-71 + GCUGGGGCGCCGCAGGUUCG 20 527

SCNNlA-52 + UGUGCUGGGAGCACACCAGG 20 584

SCNNlA-24 - GCAGCCCACGGCGGAGGAGG 20 512

SCNNlA-23 - CCAGCAGCCCACGGCGGAGG 20 566

SCNNlA-21 - GGCGCCCCAGCAGCCCACGG 20 510

SCNNlA-60 + AGAGCUCUCGGUAGGAGCGG 20 590

1357

5535.1 SCNNlA-22 - GCCCCAGCAGCCCACGGCGG 20 511

SCNNlA-6339 + GUCUGGGCUGAGCCAAAGGG 20 10188

SCNNlA-6340 - GGUGCCUGCGCCUGGAAGGG 20 10189

SCNNlA-6341 - CAGAGCCUCAGACCUGAGGG 20 10190

SCNNlA-6342 - AUGGUGGCUCCCCUUUGGGG 20 10191

SCNNlA-56 + GCGGAUGGCGCCGUGGAUGG 20 523

SCNNlA-6343 - GACAGAUAUACAAAUUAUGG 20 10192

SCNNlA-75 + AGCCCUGGAGUGGACUGUGG 20 602

SCNNlA-48 + CCCAGAAGGCCGUCUUCAUG 20 581

SCNNlA-37 + GAGGGUGCAGAUGGUCACUG 20 517

SCNNlA-74 + AUGAGCCCUGGAGUGGACUG 20 601

SCNNlA-19 - GGGGCUGGGCCCCGAACCUG 20 509

SCNNlA-6344 - CAGGCAGAGCCUCAGACCUG 20 10193

SCNNlA-67 + UCCUCCGCCGUGGGCUGCUG 20 596

SCNNlA-30 - CGGCCUUCUGGGCAGUGCUG 20 572

SCNNlA-6345 - AAGGGUGGUCCAGGGUGCUG 20 10194

SCNNlA-6346 + AGUUCCCACCCUCAGGUCUG 20 10195

SCNNlA-13 - CA U G AAG GG G AAC AAG CG U G 20 562

SCNNlA-6347 + AGAACAGGCUUGGUGUUGUG 20 10196

SCNNlA-418 + UAACCGACCUGUAGGGAUUG 20 4267

SCNNlA-40 + AGACGAGCUUGUCCGAGUUG 20 576

SCNNlA-41 + CCGAGUUGAGGUUGAUGUUG 20 577

SCNNlA-6348 - AUUAUGGUGGCUCCCCUUUG 20 10197

SCNNlA-6349 + UAUGACAGAGACCAUGCUAU 20 10198

SCNNlA-6350 + UGCCACGUCCUGCCGGGUAU 20 10199

SCNNlA-35 - CCUCAACAUCAACCUCAACU 20 574

SCNNlA-6351 - GUCUAGAAUGCUGCAGCACU 20 10200

SCNNlA-6352 - AGGGUGCUGAGGUGCUCACU 20 10201

SCNNlA-6353 + GCCAGCAGUGAGCUCUACCU 20 10202

SCNNlA-6354 + GGAGCGGGCUAGAACAGGCU 20 10203

SCNNlA-18 - AAGCGUGAGGAGCAGGGGCU 20 564

SCNNlA-66 + CUCCUCCGCCGUGGGCUGCU 20 595

SCNNlA-50 + CGUCUUCAUGCGGUUGUGCU 20 583

SCNNlA-6355 + AGGAUCAUGCACUAUCCUCU 20 10204

SCNNlA-57 + AGAAGAACUCGAAGAGCUCU 20 588

SCNNlA-6356 + AGAAUUGCAAUGCCUGGUCU 20 10205

SCNNlA-29 - CCGCAUGAAGACGGCCUUCU 20 571

SCNNlA-64 + AGGGCCUCCUCCUCCGCCGU 20 593

SCNNlA-423 - CACCCUCAAUCCCUACAGGU 20 4272

SCNNlA-58 + GAACUCGAAGAGCUCUCGGU 20 524

SCNNlA-6357 - AGAGCCUCAGACCUGAGGGU 20 10206

SCNNlA-424 + AGAGGGACUAACCGACCUGU 20 4273

1358

5535.1 SCNNlA-33 - GGCAUGAUGUACUGGCAAUU 20 515

SCNNlA-6358 + GAAAUCUGAGACCUGGACUU 20 10207

SCNNlA-31 - GUGCUGUGGCUCUGCACCUU 20 513

SCNNlA-6359 - GUGGCAGGGUCACCACCCUU 20 10208

SCNNlA-6360 - AAAUUAUGGUGGCUCCCCUU 20 10209

SCNNlA-69 + CUGCUGGGGCGCCGCAGGUU 20 597

SCNNlA-6361 - AAUUAUGGUGGCUCCCCUUU 20 10210

SCNNlA-34 - UGGCAAUUCGGCCUGCUUUU 20 573

Table 47 A provides exemplary targeting domains for knocking down the SCNNIA gene selected according to the first tier parameters. The targeting domains bind within 500 bp (e.g., upstream or downstream) of a transcription start site (TSS), have a high level of orthogonality, start with a 5'G, and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. Aureus eiCas9 molecule or eiCas9 fusion protein (e.g., an eiCas9 fused to a transcription repressor domain) to alter the SCNNIA gene (e.g., reduce or eliminate SCNNIA gene expression, SCNNIA protein function, or the level of SCNNIA protein). One or more gRNA may be used to target an eiCas9 to the promoter region of the SCNNIA gene.

Table 47A

1359

5535.1 SCNNlA-6376 + GCCAGGGAUGGAAGCGAC 18 10225

SCNNlA-6377 + GGCCAGGGAUGGAAGCGAC 19 10226

SCNNlA-6378 + GCCGGCCAGGGAUGGAAGCGAC 22 10227

SCNNlA-6379 + GGCCGGCCAGGGAUGGAAGCGAC 23 10228

SCNNlA-6380 + GAAGAAACUGACCCUUCCC 19 10229

SCNNlA-6381 + GCCCCACAGGAGGCAGCC 18 10230

SCNNlA-6382 + GGCCCCACAGGAGGCAGCC 19 10231

SCNNlA-6383 + GGGCCCCACAGGAGGCAGCC 20 10232

SCNNlA-5221 + GCUGAGGAGGAGUCAGAGCC 20 9070

SCNNlA-6384 + GCCCGCCCGCUGGCCGGCC 19 10233

SCNNlA-6385 + GAGCCCGCCCGCUGGCCGGCC 21 10234

SCNNlA-6386 + GGAGCCCGCCCGCUGGCCGGCC 22 10235

SCNNlA-6387 + GGGAGCCCGCCCGCUGGCCGGCC 23 10236

SCNNlA-6388 + GGGGAGCCCGCCCGCUGGCCGGCC 24 10237

SCNNlA-1305 + GUCAAGGCUGAGCUCUGGGCC 21 5154

SCNNlA-1306 + GGUCAAGGCUGAGCUCUGGGCC 22 5155

SCNNlA-1307 + GGGUCAAGGCUGAGCUCUGGGCC 23 5156

SCNNlA-1308 + GAGUGGAUUGGGGAGAGC 18 5157

SCNNlA-1309 + GGAGUGGAUUGGGGAGAGC 19 5158

SCNNlA-1310 + GCCCCGGAGUGGAUUGGGGAGAGC 24 5159

SCNNlA-1311 + GCCCUGGAGUGGACUGUGGAGGGC 24 5160

SCNNlA-6389 + GGAGGCAGCCCAGAGUGC 18 10238

SCNNlA-6390 + GCUGUGGUCACAGAGUUGC 19 10239

SCNNlA-1312 + GUAUGGGCUGCAGAGGUC 18 5161

SCNNlA-1313 + GGUAUGGGCUGCAGAGGUC 19 5162

SCNNlA-1314 + GACCUGGUAUGGGCUGCAGAGGUC 24 5163

SCNNlA-1315 + GAUACCUCCCCUUGGAAGGGACAG 24 5164

SCNNlA-6391 + GGACUGGUUCCUUUCCAG 18 10240

SCNNlA-6392 + GGGACUGGUUCCUUUCCAG 19 10241

SCNNlA-6393 + GACUGGGACUGGUUCCUUUCCAG 23 10242

SCNNlA-6394 + GGACUGGGACUGGUUCCUUUCCAG 24 10243

SCNNlA-6395 + GCAGCAAAAGGAUAAGGAG 19 10244

SCNNlA-6396 + GGCAAAGAUCUGAACAAGUAG 21 10245

SCNNlA-6397 + GGGCAAAGAUCUGAACAAGUAG 22 10246

SCNNlA-6398 + GGGGCAAAGAUCUGAACAAGUAG 23 10247

SCNNlA-6399 + GCAGGCACUGAAGGUGCAGG 20 10248

SCNNlA-6400 + GG G AG CAG CG CAC U C AG G 18 10249

SCNNlA-5260 + GUGGGAGCAGCGCACUCAGG 20 9109

SCNNlA-6401 + GAUUCGUCUGCUCUCUGGGUG 21 10250

SCNNlA-6402 + GGAUUCGUCUGCUCUCUGGGUG 22 10251

SCNNlA-6403 + GUGGAUUCGUCUGCUCUCUGGGUG 24

10252

1360

5535.1 SCNNlA-6404 + GCCCGUGGAUUCGUCUGCUCU 21 10253

SCNNlA-6405 + GAGCCCGUGGAUUCGUCUGCUCU 23 10254

SCNNlA-1322 + GAUUGGGGAGAGCAAGGGU 19 5171

SCNNlA-1323 + GGAUUGGGGAGAGCAAGGGU 20 5172

SCNNlA-1324 + GUGGAUUGGGGAGAGCAAGGGU 22 5173

SCNNlA-1325 + GAGUGGAUUGGGGAGAGCAAGGGU 24

5174

SCNNlA-6406 + GCAGAGCUAU A A AC AG A A U U 20 10255

SCNNlA-6407 + GAGCAGAGCUAUAAACAGAAUU 22 10256

SCNNlA-6408 + GGAGCAGAGCUAUAAACAGAAUU 23 10257

SCNNlA-6409 + GCUUCCCUGAUAGGGCCACCUU 22 10258

SCNNlA-6410 - G CCAACAG UG U AAAAAAG AA 20 10259

SCNNlA-6411 - G C AG C C A AC AG U G U A A A A A AG A A 23 10260

SCNNlA-6412 - GGCAGCCAACAGUGUAAAAAAGAA 24 10261

SCNNlA-6413 - GAGAAAAUAUAGCCCAUCA 19 10262

SCNNlA-6414 - GGAGAAAAUAUAGCCCAUCA 20 10263

SCNNlA-6415 - GCAGUCCUGGGGCAGAGA 18 10264

SCNNlA-6416 - GGUCUGGACAAGGUUGGA 18 10265

SCNNlA-6417 - GGGUCUGGACAAGGUUGGA 19 10266

SCNNlA-6418 - GAGGCAGACGCAUCCCAC 18 10267

SCNNlA-6419 - GGAGGCAGACGCAUCCCAC 19 10268

SCNNlA-6420 - GAGGAGGCAGACGCAUCCCAC 21 10269

SCNNlA-6421 - GGAGGAGGCAGACGCAUCCCAC 22 10270

SCNNlA-1335 - GGCCAGGGGCAGCCUCAC 18 5184

SCNNlA-6422 - GACCUGGCUCAAGGGAGAC 19 10271

SCNNlA-5207 - GGACCUGGCUCAAGGGAGAC 20 9056

SCNNlA-6423 - GCACCUGAGCCCCGAUCCCCC 21 10272

SCNNlA-6424 - GUGCACCUGAGCCCCGAUCCCCC 23 10273

SCNNlA-6425 - GGUGCACCUGAGCCCCGAUCCCCC 24 10274

SCNNlA-6426 - GACCAGGUUGGACCCUGAGCC 21 10275

SCNNlA-6427 - GCGUCUAAAGCCCCUGCC 18 10276

SCNNlA-6428 - GUCUGCGUCUAAAGCCCCUGCC 22 10277

SCNNlA-1336 - GCAGCCUCACUCGGGUUCC 19 5185

SCNNlA-348 - GGCAGCCUCACUCGGGUUCC 20 4197

SCNNlA-6429 - GAACCUUUGAGAUCAAACAGC 21 10278

SCNNlA-6430 - GCCUUCCCUGCCGCGUGCAGGGC 23 10279

SCNNlA-6431 - GCUUCACCUGGGCCCCUC 18 10280

SCNNlA-6432 - GUUGUGUGGGUGGCUCUC 18 10281

SCNNlA-6433 - GGUUGUGUGGGUGGCUCUC 19 10282

SCNNlA-6434 - GGGUUGUGUGGGUGGCUCUC 20 10283

SCNNlA-6435 - GGAGUUUCUAGGGGUCUC 18 10284

SCNNlA-6436 - GACUGGAGUUUCUAGGGGUCUC 22 10285

1361

5535.1 SCNNlA-6437 - GAGACUGGAGUUUCUAGGGGUCUC 24 10286

SCNNlA-6438 - GAUAACCCAGCACCCAGAGAGCAG 24 10287

SCNNlA-6439 - GAUAGCCCCAGAGGAGGAG 19 10288

SCNNlA-6440 - GUAGAUAGCCCCAGAGGAGGAG 22 10289

SCNNlA-6441 - GAGUGGGAGAAUGUGGGCG 19 10290

SCNNlA-6442 - GGAGUGGGAGAAUGUGGGCG 20 10291

SCNNlA-6443 - GACAAGGUUGGAGGGGGUGGCG 22 10292

SCNNlA-6444 - GGACAAGGUUGGAGGGGGUGGCG 23 10293

SCNNlA-6445 - GCUGCCUUAAGCUAGUGG 18 10294

SCNNlA-6446 - GCCAUGCUGCCUUAAGCUAGUGG 23 10295

SCNNlA-6447 - GUCCCAGUCCAGCCGCAACCU 21 10296

SCNNlA-6448 - GCCUGAGGGUGAGGCUGACCU 21 10297

SCNNlA-6449 - GGCCUGAGGGUGAGGCUGACCU 22 10298

SCNNlA-6450 - GGGCCUGAGGGUGAGGCUGACCU 23 10299

SCNNlA-6451 - GCCCUCCUAGCUGUGGGCU 19 10300

SCNNlA-6452 - GCUCAAGGGAGACUGGAGUUUCU 23 10301

SCNNlA-6453 - GGCUCAAGGGAGACUGGAGUUUCU 24 10302

SCNNlA-6454 - GAAUCCACGGGCUCUGUGU 19 10303

SCNNlA-6455 - GACGAAUCCACGGGCUCUGUGU 22 10304

SCNNlA-6456 - GUGCAGGGCCUGGGUUGU 18 10305

SCNNlA-6457 - GCGUGCAGGGCCUGGGUUGU 20 10306

SCNNlA-6458 - GCCGCGUGCAGGGCCUGGGUUGU 23 10307

SCNNlA-437 - GUAAGCAAGGGAACCUGGUU 20 4286

SCNNlA-1339 - GGUAAGCAAGGGAACCUGGUU 21 5188

SCNNlA-6459 - GAGUCUCCUCCAGCCCUUU 19 10308

Table 47B provides exemplary targeting domains for knocking down the SCNNIA gene selected according to the second tier parameters. The targeting domains bind within 500 bp (e.g., upstream or downstream) of a transcription start site (TSS), have a high level of orthogonality and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. Aureus eiCas9 molecule or eiCas9 fusion protein (e.g., an eiCas9 fused to a transcription repressor domain) to alter the SCNNIA gene (e.g., reduce or eliminate SCNNIA gene expression, SCNNIA protein function, or the level of SCNNIA protein). One or more gRNA may be used to target an eiCas9 to the promoter region of the SCNNIA gene.

Table 47B

2nd Tier

1362

5535.1 Target Site gRNA Name DNA Strand Targeting Domain

Length Seq ID

SCNNlA-6460 + AG A AG G AG C C AG C AC C A A A 19 10309

SCNNlA-5515 + UAGAAGGAGCCAG C AC C A A A 20 9364

SCNNlA-6461 + UAGGAGCAGAGCUAUAAA 18 10310

SCNNlA-6462 + AUAGGAGCAGAGCUAUAAA 19 10311

SCNNlA-6463 + AAUAGGAGCAGAGCUAUAAA 20 10312

SCNNlA-6464 + AAA UAGGAGCAGAGCUAU AAA 21 10313

SCNNlA-6465 + A A A A UAGGAGCAGAGCUAU AAA 22 10314

SCNNlA-6466 + CAAAAUAGGAGCAGAGCUAUAAA 23 10315

SCNNlA-6467 + ACAAAAUAGGAGCAGAGCUAUAAA 24 10316

SCNNlA-6468 + UUUCCAAACUUAAUGCAGCAA 21 10317

SCNNlA-6469 + CUUUCCAAACUUAAUGCAGCAA 22 10318

SCNNlA-6470 + UCUUUCCAAACUUAAUGCAGCAA 23 10319

SCNNlA-6471 + CUCUUUCCAAACUUAAUGCAGCAA 24 10320

SCNNlA-6472 + UGGCCAGCGCUGGAAAGGAA 20 10321

SCNNlA-6473 + UGUGGCCAGCGCUGGAAAGGAA 22 10322

SCNNlA-6474 + AUGUGGCCAGCGCUGGAAAGGAA 23 10323

SCNNlA-6475 + UGCUGAAUCUUGACAAGCA 19 10324

SCNNlA-5532 + CUGCUGAAUCUUGACAAGCA 20 9381

SCNNlA-6476 + UCUGCUGAAUCUUGACAAGCA 21 10325

SCNNlA-6477 + CUCUGCUGAAUCUUGACAAGCA 22 10326

SCNNlA-6478 + UCUCUGCUGAAUCUUGACAAGCA 23 10327

SCNNlA-6479 + AUCUCUGCUGAAUCUUGACAAGCA 24 10328

SCNNlA-6480 + AGGGAUGGAGGAGGGGCA 18 10329

SCNNlA-6481 + UAGGGAUGGAGGAGGGGCA 19 10330

SCNNlA-6482 + AUAGGGAUGGAGGAGGGGCA 20 10331

SCNNlA-6483 + UCGCCCCUGCUGUGGUCA 18 10332

SCNNlA-6484 + AUCGCCCCUGCUGUGGUCA 19 10333

SCNNlA-6485 + AAUCGCCCCUGCUGUGGUCA 20 10334

SCNNlA-6486 + UAAUCGCCCCUGCUGUGGUCA 21 10335

SCNNlA-6487 + UGUAAUCGCCCCUGCUGUGGUCA 23 10336

SCNNlA-6488 + U A A U G C AG C A A A AG G A U A 18 10337

SCNNlA-6489 + U U A A U G C AG C A A A AG G A U A 19 10338

SCNNlA-6098 + CUUAAUGCAGCAAAAGGAUA 20 9947

SCNNlA-6490 + AGUGAAAGCCGGUGUCAAC 19 10339

SCNNlA-6491 + A AG U G AAAG CCGGUGUCAAC 20 10340

SCNNlA-6492 + AAAG U G AAAG CCGGUGUCAAC 21 10341

SCNNlA-6493 + UAAAGUGAAAGCCGGUGUCAAC 22 10342

SCNNlA-6494 + U U AAAG UG AAAG CCGG UG U CAAC 23 10343

SCNNlA-6495 + CU U AAAG UG AAAG CCGG UG U CAAC 24 10344

SCNNlA-1344 + UCCCAUCACCCCUGGAAC 18 5193

1363

5535.1 SCNNlA-1345 + CUCCCAUCACCCCUGGAAC 19 5194

SCNNlA-1346 + UCUCCCAUCACCCCUGGAAC 20 5195

SCNNlA-1347 + CUCUCCCAUCACCCCUGGAAC 21 5196

SCNNlA-1348 + CCUCUCCCAUCACCCCUGGAAC 22 5197

SCNNlA-1349 + CCCUCUCCCAUCACCCCUGGAAC 23 5198

SCNNlA-6496 + AUCGGGGCUCAGGUGCAC 18 10345

SCNNlA-6497 + UGGGGGAUCGGGGCUCAGGUGCAC 24 10346

SCNNlA-5564 + CGGCCAGGGAUGGAAGCGAC 20 9413

SCNNlA-6498 + CCGGCCAGGGAUGGAAGCGAC 21 10347

SCNNlA-6499 + UGGCCGGCCAGGGAUGGAAGCGAC 24 10348

SCNNlA-6500 + CACUCCCACACAGAGCCC 18 10349

SCNNlA-6501 + UCACUCCCACACAGAGCCC 19 10350

SCNNlA-6502 + CUCACUCCCACACAGAGCCC 20 10351

SCNNlA-6503 + AAGAAACUGACCCUUCCC 18 10352

SCNNlA-6504 + UGAAGAAACUGACCCUUCCC 20 10353

SCNNlA-6505 + AUGAAGAAACUGACCCUUCCC 21 10354

SCNNlA-6506 + AAUGAAGAAACUGACCCUUCCC 22 10355

SCNNlA-6507 + UAAUGAAGAAACUGACCCUUCCC 23 10356

SCNNlA-6508 + CUAAUGAAGAAACUGACCCUUCCC 24 10357

SCNNlA-6509 + CGGGCCCCACAGGAGGCAGCC 21 10358

SCNNlA-6510 + ACGGGCCCCACAGGAGGCAGCC 22 10359

SCNNlA-6511 + CACGGGCCCCACAGGAGGCAGCC 23 10360

SCNNlA-6512 + UCACGGGCCCCACAGGAGGCAGCC 24 10361

SCNNlA-6513 + UGAGGAGGAGUCAGAGCC 18 10362

SCNNlA-6514 + CUGAGGAGGAGUCAGAGCC 19 10363

SCNNlA-6515 + ACUGUUGGCUGCCAGGCC 18 10364

SCNNlA-6516 + CACUGUUGGCUGCCAGGCC 19 10365

SCNNlA-5583 + ACACUGUUGGCUGCCAGGCC 20 9432

SCNNlA-6517 + UACACUGUUGGCUGCCAGGCC 21 10366

SCNNlA-6518 + UUACACUGUUGGCUGCCAGGCC 22 10367

SCNNlA-6519 + UUUACACUGUUGGCUGCCAGGCC 23 10368

SCNNlA-6520 + UUUUACACUGUUGGCUGCCAGGCC 24 10369

SCNNlA-6521 + CCCGCCCGCUGGCCGGCC 18 10370

SCNNlA-6109 + AGCCCGCCCGCUGGCCGGCC 20 9958

SCNNlA-1350 + AAGGCUGAGCUCUGGGCC 18 5199

SCNNlA-1351 + CAAGGCUGAGCUCUGGGCC 19 5200

SCNNlA-1352 + UCAAGGCUGAGCUCUGGGCC 20 5201

SCNNlA-1353 + AGGGUCAAGGCUGAGCUCUGGGCC 24 5202

SCNNlA-1354 + CGGAGUGGAUUGGGGAGAGC 20 5203

SCNNlA-1355 + CCGGAGUGGAUUGGGGAGAGC 21 5204

SCNNlA-1356 + CCCGGAGUGGAUUGGGGAGAGC 22 5205

SCNNlA-1357 + CCCCGGAGUGGAUUGGGGAGAGC 23 5206

1364

5535.1 SCNNlA-1358 + CUGGAGUGGACUGUGGAGGGC 21 5207

SCNNlA-1359 + CCUGGAGUGGACUGUGGAGGGC 22 5208

SCNNlA-1360 + CCCUGGAGUGGACUGUGGAGGGC 23 5209

SCNNlA-6522 + UGGAGCCAGCAGACCUGC 18 10371

SCNNlA-6523 + CUGGAGCCAGCAGACCUGC 19 10372

SCNNlA-5615 + CCUGGAGCCAGCAGACCUGC 20 9464

SCNNlA-6524 + AGGAGGCAGCCCAGAGUGC 19 10373

SCNNlA-6130 + CAGGAGGCAGCCCAGAGUGC 20 9979

SCNNlA-6525 + ACAGGAGGCAGCCCAGAGUGC 21 10374

SCNNlA-6526 + CACAGGAGGCAGCCCAGAGUGC 22 10375

SCNNlA-6527 + CCACAGGAGGCAGCCCAGAGUGC 23 10376

SCNNlA-6528 + CCCACAGGAGGCAGCCCAGAGUGC 24 10377

SCNNlA-6529 + CUGUGGUCACAGAGUUGC 18 10378

SCNNlA-5623 + UGCUGUGGUCACAGAGUUGC 20 9472

SCNNlA-6530 + CUGCUGUGGUCACAGAGUUGC 21 10379

SCNNlA-6531 + CCUGCUGUGGUCACAGAGUUGC 22 10380

SCNNlA-6532 + CCCUGCUGUGGUCACAGAGUUGC 23 10381

SCNNlA-6533 + CCCCUGCUGUGGUCACAGAGUUGC 24 10382

SCNNlA-6534 + CCUUUGGUCUUCUUCCUC 18 10383

SCNNlA-6535 + UCCUUUGGUCUUCUUCCUC 19 10384

SCNNlA-6536 + UUCCUUUGGUCUUCUUCCUC 20 10385

SCNNlA-1361 + UGGUAUGGGCUGCAGAGGUC 20 5210

SCNNlA-1362 + CUGGUAUGGGCUGCAGAGGUC 21 5211

SCNNlA-1363 + CCUGGUAUGGGCUGCAGAGGUC 22 5212

SCNNlA-1364 + ACCUGGUAUGGGCUGCAGAGGUC 23 5213

SCNNlA-1365 + UCCCCUUGGAAGGGACAG 18 5214

SCNNlA-1366 + CUCCCCUUGGAAGGGACAG 19 5215

SCNNlA-1367 + CCUCCCCUUGGAAGGGACAG 20 5216

SCNNlA-1368 + ACCUCCCCUUGGAAGGGACAG 21 5217

SCNNlA-1369 + UACCUCCCCUUGGAAGGGACAG 22 5218

SCNNlA-1370 + AUACCUCCCCUUGGAAGGGACAG 23 5219

SCNNlA-6537 + UGGGACUGGUUCCUUUCCAG 20 10386

SCNNlA-6538 + CUGGGACUGGUUCCUUUCCAG 21 10387

SCNNlA-6539 + ACUGGGACUGGUUCCUUUCCAG 22 10388

SCNNlA-6540 + CAGCAAAAGGAUAAGGAG 18 10389

SCNNlA-5654 + UGCAGCAAAAGGAUAAGGAG 20 9503

SCNNlA-6541 + AUGCAGCAAAAGGAUAAGGAG 21 10390

SCNNlA-6542 + AAUGCAGCAAAAGGAUAAGGAG 22 10391

SCNNlA-6543 + UAAUGCAGCAAAAGGAUAAGGAG 23 10392

SCNNlA-6544 + UUAAUGCAGCAAAAGGAUAAGGAG 24 10393

SCNNlA-6545 + UAUCAAGGGCUCUGUGAG 18 10394

SCNNlA-6546 + AUAUCAAGGGCUCUGUGAG 19 10395

1365

5535.1 SCNNlA-6547 + CAUAUCAAGGGCUCUGUGAG 20 10396

SCNNlA-6548 + UCAUAUCAAGGGCUCUGUGAG 21 10397

SCNNlA-6549 + UUCAUAUCAAGGGCUCUGUGAG 22 10398

SCNNlA-6550 + UUUCAUAUCAAGGGCUCUGUGAG 23 10399

SCNNlA-6551 + UUUUCAUAUCAAGGGCUCUGUGAG 24 10400

SCNNlA-6552 + AGGGGCAAAGAUCUGAACAAGUAG 24 10401

SCNNlA-6553 + AGGCACUGAAGGUGCAGG 18 10402

SCNNlA-6554 + C AGG CAC U G AAG G U G C AG G 19 10403

SCNNlA-6555 + UGGGAGCAGCGCACUCAGG 19 10404

SCNNlA-6556 + AGUGGGAGCAGCGCACUCAGG 21 10405

SCNNlA-6557 + AAGUGGGAGCAGCGCACUCAGG 22 10406

SCNNlA-6558 + UAAGUGGGAGCAGCGCACUCAGG 23 10407

SCNNlA-6559 + CUAAGUGGGAGCAGCGCACUCAGG 24 10408

SCNNlA-6560 + CAGGAAGGAGAGCAAGGG 18 10409

SCNNlA-6561 + CCAGGAAGGAGAGCAAGGG 19 10410

SCNNlA-6159 + UCCAGGAAGGAGAGCAAGGG 20 10008

SCNNlA-6562 + UCCUGAGACAGACUCAUG 18 10411

SCNNlA-6563 + UUCCUGAGACAGACUCAUG 19 10412

SCNNlA-5698 + CUUCCUGAGACAGACUCAUG 20 9547

SCNNlA-6564 + ACUUCCUGAGACAGACUCAUG 21 10413

SCNNlA-6565 + UACUUCCUGAGACAGACUCAUG 22 10414

SCNNlA-6566 + UUACUUCCUGAGACAGACUCAUG 23 10415

SCNNlA-6567 + UUUACUUCCUGAGACAGACUCAUG 24 10416

SCNNlA-6568 + UCGUCUGCUCUCUGGGUG 18 10417

SCNNlA-6569 + UUCGUCUGCUCUCUGGGUG 19 10418

SCNNlA-6570 + AUUCGUCUGCUCUCUGGGUG 20 10419

SCNNlA-6571 + UGGAUUCGUCUGCUCUCUGGGUG 23 10420

SCNNlA-6572 + AGCGAAGGACAGAGAGAU 18 10421

SCNNlA-6573 + CAGCGAAGGACAGAGAGAU 19 10422

SCNNlA-5722 + ACAGCGAAGGACAGAGAGAU 20 9571

SCNNlA-6574 + CCCGAGGGCAGGUGAACU 18 10423

SCNNlA-6575 + UCCCGAGGGCAGGUGAACU 19 10424

SCNNlA-5726 + CUCCCGAGGGCAGGUGAACU 20 9575

SCNNlA-6576 + AAGGCAGUACUCCAGGCU 18 10425

SCNNlA-6577 + AAAGGCAGUACUCCAGGCU 19 10426

SCNNlA-6578 + AAAAG G C AG U AC U CC AG G C U 20 10427

SCNNlA-6579 + CGUGGAUUCGUCUGCUCU 18 10428

SCNNlA-6580 + CCGUGGAUUCGUCUGCUCU 19 10429

SCNNlA-6581 + CCCGUGGAUUCGUCUGCUCU 20 10430

SCNNlA-6582 + AGCCCGUGGAUUCGUCUGCUCU 22 10431

SCNNlA-6583 + AGAGCCCGUGGAUUCGUCUGCUCU 24 10432

SCNNlA-6584 + UCUGCCUUCUGUUUCUCU 18 10433

1366

5535.1 SCNNlA-6585 + AUCUGCCUUCUGUUUCUCU 19 10434

SCNNlA-6586 + UAUCUGCCUUCUGUUUCUCU 20 10435

SCNNlA-6587 + CUAUCUGCCUUCUGUUUCUCU 21 10436

SCNNlA-6588 + UCUAUCUGCCUUCUGUUUCUCU 22 10437

SCNNlA-6589 + CUCUAUCUGCCUUCUGUUUCUCU 23 10438

SCNNlA-6590 + UCUCUAUCUGCCUUCUGUUUCUCU 24 10439

SCNNlA-1377 + AUUGGGGAGAGCAAGGGU 18 5226

SCNNlA-1378 + UGGAUUGGGGAGAGCAAGGGU 21 5227

SCNNlA-1379 + AGUGGAUUGGGGAGAGCAAGGGU 23 5228

SCNNlA-6591 + AGAGCUAUAAACAGAAUU 18 10440

SCNNlA-6592 + CAGAGCUAU A A AC AG A A U U 19 10441

SCNNlA-6593 + AGCAGAGCUAU A A AC AG A A U U 21 10442

SCNNlA-6594 + AGGAGCAGAGCUAUAAACAGAAUU 24 10443

SCNNlA-6595 + CUUCCCUGAUAGGGCCACCUU 21 10444

SCNNlA-6596 + UGCUUCCCUGAUAGGGCCACCUU 23 10445

SCNNlA-6597 + CUGCUUCCCUGAUAGGGCCACCUU 24 10446

SCNNlA-6598 - CAACAGUGUAAAAAAGAA 18 10447

SCNNlA-6599 - CCAACAGUGUAAAAAAGAA 19 10448

SCNNlA-6600 - AG CCAACAGUGUAAAAAAGAA 21 10449

SCNNlA-6601 - CAG CCAACAG U GUAAAAAAGAA 22 10450

SCNNlA-6602 - AGAAAAUAUAGCCCAUCA 18 10451

SCNNlA-6603 - UGCAGUCCUGGGGCAGAGA 19 10452

SCNNlA-6604 - CUGCAGUCCUGGGGCAGAGA 20 10453

SCNNlA-5553 - CGGGUCUGGACAAGGUUGGA 20 9402

SCNNlA-6605 - CCGGGUCUGGACAAGGUUGGA 21 10454

SCNNlA-6606 - CCCGGGUCUGGACAAGGUUGGA 22 10455

SCNNlA-6607 - UCCCGGGUCUGGACAAGGUUGGA 23 10456

SCNNlA-6608 - CUCCCGGGUCUGGACAAGGUUGGA 24 10457

SCNNlA-6609 - AGGAGGCAGACGCAUCCCAC 20 10458

SCNNlA-6610 - AGGAGGAGGCAGACGCAUCCCAC 23 10459

SCNNlA-6611 - CAGGAGGAGGCAGACGCAUCCCAC 24 10460

SCNNlA-1392 - UGGCCAGGGGCAGCCUCAC 19 5241

SCNNlA-1393 - AUGGCCAGGGGCAGCCUCAC 20 5242

SCNNlA-6612 - ACCUGGCUCAAGGGAGAC 18 10461

SCNNlA-6613 - CCUGAGCCCCGAUCCCCC 18 10462

SCNNlA-6614 - ACCUGAGCCCCGAUCCCCC 19 10463

SCNNlA-6615 - CACCUGAGCCCCGAUCCCCC 20 10464

SCNNlA-6616 - UGCACCUGAGCCCCGAUCCCCC 22 10465

SCNNlA-6617 - CAGGUUGGACCCUGAGCC 18 10466

SCNNlA-6618 - CCAGGUUGGACCCUGAGCC 19 10467

SCNNlA-5581 - ACCAGGUUGGACCCUGAGCC 20 9430

SCNNlA-6619 - AGACCAGGUUGGACCCUGAGCC 22 10468

1367

5535.1 SCNNlA-6620 - CAGACCAGGUUGGACCCUGAGCC 23 10469

SCNNlA-6621 - ACAGACCAGGUUGGACCCUGAGCC 24 10470

SCNNlA-6622 - UGCGUCUAAAGCCCCUGCC 19 10471

SCNNlA-6623 - CUGCGUCUAAAGCCCCUGCC 20 10472

SCNNlA-6624 - UCUGCGUCUAAAGCCCCUGCC 21 10473

SCNNlA-6625 - UGUCUGCGUCUAAAGCCCCUGCC 23 10474

SCNNlA-6626 - CUGUCUGCGUCUAAAGCCCCUGCC 24 10475

SCNNlA-1394 - CAGCCUCACUCGGGUUCC 18 5243

SCNNlA-6627 - CCUUUGAGAUCAAACAGC 18 10476

SCNNlA-6628 - ACCUUUGAGAUCAAACAGC 19 10477

SCNNlA-6629 - AACCUUUGAGAUCAAACAGC 20 10478

SCNNlA-6630 - AGAACCUUUGAGAUCAAACAGC 22 10479

SCNNlA-6631 - CAGAACCUUUGAGAUCAAACAGC 23 10480

SCNNlA-6632 - UCAGAACCUUUGAGAUCAAACAGC 24 10481

SCNNlA-6633 - CCCUGCCGCGUGCAGGGC 18 10482

SCNNlA-6634 - UCCCUGCCGCGUGCAGGGC 19 10483

SCNNlA-6635 - UUCCCUGCCGCGUGCAGGGC 20 10484

SCNNlA-6636 - CUUCCCUGCCGCGUGCAGGGC 21 10485

SCNNlA-6637 - CCUUCCCUGCCGCGUGCAGGGC 22 10486

SCNNlA-6638 - AGCCUUCCCUGCCGCGUGCAGGGC 24 10487

SCNNlA-6639 - AGCUUCACCUGGGCCCCUC 19 10488

SCNNlA-6640 - CAGCUUCACCUGGGCCCCUC 20 10489

SCNNlA-6641 - CCAGCUUCACCUGGGCCCCUC 21 10490

SCNNlA-6642 - CCCAGCUUCACCUGGGCCCCUC 22 10491

SCNNlA-6643 - CCCCAGCUUCACCUGGGCCCCUC 23 10492

SCNNlA-6644 - CCCCCAGCUUCACCUGGGCCCCUC 24 10493

SCNNlA-6645 - UGGAGUUUCUAGGGGUCUC 19 10494

SCNNlA-5635 - CUGGAGUUUCUAGGGGUCUC 20 9484

SCNNlA-6646 - ACUGGAGUUUCUAGGGGUCUC 21 10495

SCNNlA-6647 - AGACUGGAGUUUCUAGGGGUCUC 23 10496

SCNNlA-6648 - CCAGCACCCAGAGAGCAG 18 10497

SCNNlA-6649 - CCCAG CACCCAG AG AG CAG 19 10498

SCNNlA-6650 - ACCCAGCACCCAGAGAGCAG 20 10499

SCNNlA-6651 - AACCCAGCACCCAGAGAGCAG 21 10500

SCNNlA-6652 - UAACCCAGCACCCAGAGAGCAG 22 10501

SCNNlA-6653 - AUAACCCAGCACCCAGAGAGCAG 23 10502

SCNNlA-6654 - AUAGCCCCAGAGGAGGAG 18 10503

SCNNlA-6655 - AGAUAGCCCCAGAGGAGGAG 20 10504

SCNNlA-6656 - UAGAUAGCCCCAGAGGAGGAG 21 10505

SCNNlA-6657 - AGUAGAUAGCCCCAGAGGAGGAG 23 10506

SCNNlA-6658 - AAGUAGAUAGCCCCAGAGGAGGAG 24 10507

SCNNlA-6659 - AGUGGGAGAAUGUGGGCG 18 10508

1368

5535.1 SCNNlA-6660 - AGGUUGGAGGGGGUGGCG 18 10509

SCNNlA-6661 - AAGGUUGGAGGGGGUGGCG 19 10510

SCNNlA-5670 - CAAGGUUGGAGGGGGUGGCG 20 9519

SCNNlA-6662 - ACAAGGUUGGAGGGGGUGGCG 21 10511

SCNNlA-6663 - UGGACAAGGUUGGAGGGGGUGGCG 24

10512

SCNNlA-6664 - AACUGAUUUAUCCUUGGG 18 10513

SCNNlA-6665 - AAACUGAUUUAUCCUUGGG 19 10514

SCNNlA-6666 - AAAACUGAUUUAUCCUUGGG 20 10515

SCNNlA-6667 - UGCUGCCUUAAGCUAGUGG 19 10516

SCNNlA-6668 - AUGCUGCCUUAAGCUAGUGG 20 10517

SCNNlA-6669 - CAUGCUGCCUUAAGCUAGUGG 21 10518

SCNNlA-6670 - CCAUGCUGCCUUAAGCUAGUGG 22 10519

SCNNlA-6671 - UGCCAUGCUGCCUUAAGCUAGUGG 24 10520

SCNNlA-6672 - CCAGUCCAGCCGCAACCU 18 10521

SCNNlA-6673 - CCCAG U CCAG CCG CAACCU 19 10522

SCNNlA-5731 - UCCCAGUCCAGCCGCAACCU 20 9580

SCNNlA-6674 - AG U CCCAG U CCAG CCG CAACCU 22 10523

SCNNlA-6675 - CAG U CCCAG U CCAG CCG CAACCU 23 10524

SCNNlA-6676 - CCAGUCCCAGUCCAGCCGCAACCU 24 10525

SCNNlA-6677 - UGAGGGUGAGGCUGACCU 18 10526

SCNNlA-6678 - CUGAGGGUGAGGCUGACCU 19 10527

SCNNlA-6679 - CCUGAGGGUGAGGCUGACCU 20 10528

SCNNlA-6680 - AGGGCCUGAGGGUGAGGCUGACCU 24 10529

SCNNlA-6681 - CUCUUCUCUGCAGGGCCU 18 10530

SCNNlA-6682 - UCUCUUCUCUGCAGGGCCU 19 10531

SCNNlA-6683 - CUCUCUUCUCUGCAGGGCCU 20 10532

SCNNlA-6684 - UCUCUCUUCUCUGCAGGGCCU 21 10533

SCNNlA-6685 - UUCUCUCUUCUCUGCAGGGCCU 22 10534

SCNNlA-6686 - CUUCUCUCUUCUCUGCAGGGCCU 23 10535

SCNNlA-6687 - UCUUCUCUCUUCUCUGCAGGGCCU 24 10536

SCNNlA-6688 - CCUGCCUCUUCCUGGGCU 18 10537

SCNNlA-6689 - CCCUGCCUCUUCCUGGGCU 19 10538

SCNNlA-6690 - UCCCUGCCUCUUCCUGGGCU 20 10539

SCNNlA-6691 - CCCUCCUAGCUGUGGGCU 18 10540

SCNNlA-6692 - UGCCCUCCUAGCUGUGGGCU 20 10541

SCNNlA-6693 - AGGGAGACUGGAGUUUCU 18 10542

SCNNlA-6694 - AAGGGAGACUGGAGUUUCU 19 10543

SCNNlA-5751 - CAAGGGAGACUGGAGUUUCU 20 9600

SCNNlA-6695 - UCAAGGGAGACUGGAGUUUCU 21 10544

SCNNlA-6696 - CUCAAGGGAGACUGGAGUUUCU 22 10545

SCNNlA-6697 - AAUCCACGGGCUCUGUGU 18 10546

1369

5535.1 SCNNlA-5766 - CGAAUCCACGGGCUCUGUGU 20 9615

SCNNlA-6698 - ACGAAUCCACGGGCUCUGUGU 21 10547

SCNNlA-6699 - AGACGAAUCCACGGGCUCUGUGU 23 10548

SCNNlA-6700 - CAGACGAAUCCACGGGCUCUGUGU 24 10549

SCNNlA-6701 - CGUGCAGGGCCUGGGUUGU 19 10550

SCNNlA-6702 - CGCGUGCAGGGCCUGGGUUGU 21 10551

SCNNlA-6703 - CCGCGUGCAGGGCCUGGGUUGU 22 10552

SCNNlA-6704 - UGCCGCGUGCAGGGCCUGGGUUGU 24 10553

SCNNlA-1405 - AAGCAAGGGAACCUGGUU 18 5254

SCNNlA-1406 - UAAGCAAGGGAACCUGGUU 19 5255

SCNNlA-1407 - AGGUAAGCAAGGGAACCUGGUU 22 5256

SCNNlA-1408 - A AG G U A AG C A AG GGAACCUGGUU 23 5257

SCNNlA-1409 - C A AG G U A AG C A AG GGAACCUGGUU 24 5258

SCNNlA-6705 - AGUCUCCUCCAGCCCUUU 18 10554

SCNNlA-6706 - CGAGUCUCCUCCAGCCCUUU 20 10555

SCNNlA-6707 - CCGAGUCUCCUCCAGCCCUUU 21 10556

SCNNlA-6708 - CCCGAGUCUCCUCCAGCCCUUU 22 10557

SCNNlA-6709 - UCCCGAGUCUCCUCCAGCCCUUU 23 10558

SCNNlA-6710 - CUCCCGAGUCUCCUCCAGCCCUUU 24 10559

Table 47C provides exemplary targeting domains for knocking down the SCNNIA gene selected according to the third tier parameters. The targeting domains bind within 500 bp (e.g., upstream or downstream) of a transcription start site (TSS), and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. Aureus eiCas9 molecule or eiCas9 fusion protein (e.g., an eiCas9 fused to a transcription repressor domain) to alter the SCNNIA gene (e.g., reduce or eliminate SCNNIA gene expression, SCNNIA protein function, or the level of SCNNIA protein). One or more gRNA may be used to target an eiCas9 to the promoter region of the SCNNIA gene

Table 47C

1370

5535.1 SCNNlA-6715 + CCAAACUUAAUGCAGCAA 18 10564

SCNNlA-6716 + U C C A A AC U UAAUGCAGCAA 19 10565

SCNNlA-6717 + UUCCAAACUUAAUGCAGCAA 20 10566

SCNNlA-6718 + GAUAGGGAUGGAGGAGGGGCA 21 10567

SCNNlA-6719 + AGAUAGGGAUGGAGGAGGGGCA 22 10568

SCNNlA-6720 + GAGAUAGGGAUGGAGGAGGGGCA 23 10569

SCNNlA-6721 + AGAGAUAGGGAUGGAGGAGGGGCA 24

10570

SCNNlA-6722 + GGAGAGAGAGGAGGGUCA 18 10571

SCNNlA-6723 + AGGAGAGAGAGGAGGGUCA 19 10572

SCNNlA-6724 + AAGGAGAGAGAGGAGGGUCA 20 10573

SCNNlA-6725 + CAAGGAGAGAGAGGAGGGUCA 21 10574

SCNNlA-6726 + GCAAGGAGAGAGAGGAGGGUCA 22 10575

SCNNlA-6727 + AGCAAGGAGAGAGAGGAGGGUCA 23 10576

SCNNlA-6728 + GAGCAAGGAGAGAGAGGAGGGUCA 24 10577

SCNNlA-1410 + CCCUUCAUGAGCCCCGGA 18 5259

SCNNlA-1411 + CCCCUUCAUGAGCCCCGGA 19 5260

SCNNlA-1412 + UCCCCUUCAUGAGCCCCGGA 20 5261

SCNNlA-1413 + UUCCCCUUCAUGAGCCCCGGA 21 5262

SCNNlA-1414 + GUUCCCCUUCAUGAGCCCCGGA 22 5263

SCNNlA-1415 + UGUUCCCCUUCAUGAGCCCCGGA 23 5264

SCNNlA-1416 + UUGUUCCCCUUCAUGAGCCCCGGA 24 5265

SCNNlA-6729 + GGCAAGGAGGCUGGGGGA 18 10578

SCNNlA-6730 + AGGCAAGGAGGCUGGGGGA 19 10579

SCNNlA-6731 + CAGGCAAGGAGGCUGGGGGA 20 10580

SCNNlA-6732 + ACAGGCAAGGAGGCUGGGGGA 21 10581

SCNNlA-6733 + GACAGGCAAGGAGGCUGGGGGA 22 10582

SCNNlA-6734 + AGACAGGCAAGGAGGCUGGGGGA 23 10583

SCNNlA-6735 + CAGACAGGCAAGGAGGCUGGGGGA 24 10584

SCNNlA-6736 + AUGGAGGAGGGGCACUGA 18 10585

SCNNlA-6737 + GAUGGAGGAGGGGCACUGA 19 10586

SCNNlA-6738 + GGAUGGAGGAGGGGCACUGA 20 10587

SCNNlA-6739 + GGGAUGGAGGAGGGGCACUGA 21 10588

SCNNlA-6740 + AGGGAUGGAGGAGGGGCACUGA 22 10589

SCNNlA-6741 + UAGGGAUGGAGGAGGGGCACUGA 23 10590

SCNNlA-6742 + AUAGGGAUGGAGGAGGGGCACUGA 24

10591

SCNNlA-6743 + ACUUAAUGCAGCAAAAGGAUA 21 10592

SCNNlA-6744 + AACUUAAUGCAGCAAAAGGAUA 22 10593

SCNNlA-6745 + AAACUUAAUGCAGCAAAAGGAUA 23 10594

SCNNlA-6746 + C A A AC U U A A U G C AG C A A A AG G A U A 24 10595

SCNNlA-6747 + CCUCACUCCCACACAGAGCCC 21 10596

1371

5535.1 SCNNlA-6748 + CCCUCACUCCCACACAGAGCCC 22 10597

SCNNlA-6749 + UCCCUCACUCCCACACAGAGCCC 23 10598

SCNNlA-6750 + CUCCCUCACUCCCACACAGAGCCC 24 10599

SCNNlA-1417 + GUUCCCCUUCAUGAGCCC 18 5266

SCNNlA-1418 + UGUUCCCCUUCAUGAGCCC 19 5267

SCNNlA-72 + UUGUUCCCCUUCAUGAGCCC 20 599

SCNNlA-1419 + CUUGUUCCCCUUCAUGAGCCC 21 5268

SCNNlA-1420 + GCUUGUUCCCCUUCAUGAGCCC 22 5269

SCNNlA-1421 + AGCUUGUUCCCCUUCAUGAGCCC 23 5270

SCNNlA-1422 + CAGCUUGUUCCCCUUCAUGAGCCC 24 5271

SCNNlA-6751 + GGCUGAGGAGGAGUCAGAGCC 21 10600

SCNNlA-6752 + GGGCUGAGGAGGAGUCAGAGCC 22 10601

SCNNlA-6753 + GGGGCUGAGGAGGAGUCAGAGCC 23 10602

SCNNlA-6754 + AGGGGCUGAGGAGGAGUCAGAGCC 24 10603

SCNNlA-6755 + CAGCCAGGCUGAGAGGGC 18 10604

SCNNlA-6756 + CCAGCCAGGCUGAGAGGGC 19 10605

SCNNlA-6757 + GCCAGCCAGGCUGAGAGGGC 20 10606

SCNNlA-6758 + GGCCAGCCAGGCUGAGAGGGC 21 10607

SCNNlA-6759 + GGGCCAGCCAGGCUGAGAGGGC 22 10608

SCNNlA-6760 + GGGGCCAGCCAGGCUGAGAGGGC 23 10609

SCNNlA-6761 + AGGGGCCAGCCAGGCUGAGAGGGC 24 10610

SCNNlA-1431 + GAGUGGACUGUGGAGGGC 18 5280

SCNNlA-1432 + GGAGUGGACUGUGGAGGGC 19 5281

SCNNlA-201 + UGGAGUGGACUGUGGAGGGC 20 830

SCNNlA-6762 + UCCUGGAGCCAGCAGACCUGC 21 10611

SCNNlA-6763 + UUCCUGGAGCCAGCAGACCUGC 22 10612

SCNNlA-6764 + UUUCCUGGAGCCAGCAGACCUGC 23 10613

SCNNlA-6765 + CUUUCCUGGAGCCAGCAGACCUGC 24 10614

SCNNlA-6766 + CUUCCUUUGGUCUUCUUCCUC 21 10615

SCNNlA-6767 + CCUUCCUUUGGUCUUCUUCCUC 22 10616

SCNNlA-6768 + CCCUUCCUUUGGUCUUCUUCCUC 23 10617

SCNNlA-6769 + CCCCUUCCUUUGGUCUUCUUCCUC 24 10618

SCNNlA-6770 + GUGAGCAAGGAGAGAGAG 18 10619

SCNNlA-6771 + GGUGAGCAAGGAGAGAGAG 19 10620

SCNNlA-6772 + UGGUGAGCAAGGAGAGAGAG 20 10621

SCNNlA-6773 + GUGGUGAGCAAGGAGAGAGAG 21 10622

SCNNlA-6774 + AGUGGUGAGCAAGGAGAGAGAG 22 10623

SCNNlA-6775 + AAGUGGUGAGCAAGGAGAGAGAG 23 10624

SCNNlA-6776 + CAAGUGGUGAGCAAGGAGAGAGAG 24 10625

SCNNlA-6777 + AAAGAUCUGAACAAGUAG 18 10626

SCNNlA-6778 + C AAAG AU C U G AAC AAG U AG 19 10627

SCNNlA-6779 + G C A A AG A U C U G A AC A AG U AG 20 10628

1372

5535.1 SCNNlA-6780 + AGCAGGCACUGAAGGUGCAGG 21 10629

SCNNlA-6781 + AAGCAGGCACUGAAGGUGCAGG 22 10630

SCNNlA-6782 + A A AG CAGGCACUGAAGGUGCAGG 23 10631

SCNNlA-6783 + G A A AG CAGGCACUGAAGGUGCAGG 24 10632

SCNNlA-6784 + CGGGGGGAGGGGCUGAGG 18 10633

SCNNlA-6785 + GCGGGGGGAGGGGCUGAGG 19 10634

SCNNlA-5907 + GGCGGGGGGAGGGGCUGAGG 20 9756

SCNNlA-6786 + GGGCGGGGGGAGGGGCUGAGG 21 10635

SCNNlA-6787 + AGGGCGGGGGGAGGGGCUGAGG 22 10636

SCNNlA-6788 + CAGGGCGGGGGGAGGGGCUGAGG 23 10637

SCNNlA-6789 + GCAGGGCGGGGGGAGGGGCUGAGG 24

10638

SCNNlA-6790 + CUCCAGGAAGGAGAGCAAGGG 21 10639

SCNNlA-6791 + UCUCCAGGAAGGAGAGCAAGGG 22 10640

SCNNlA-6792 + GUCUCCAGGAAGGAGAGCAAGGG 23 10641

SCNNlA-6793 + UGUCUCCAGGAAGGAGAGCAAGGG 24 10642

SCNNlA-6794 + GAGAAGGUGUCAUCUCUG 18 10643

SCNNlA-6795 + AGAGAAGGUGUCAUCUCUG 19 10644

SCNNlA-6796 + CAGAGAAGGUGUCAUCUCUG 20 10645

SCNNlA-6797 + CCAGAGAAGGUGUCAUCUCUG 21 10646

SCNNlA-6798 + CCCAGAGAAGGUGUCAUCUCUG 22 10647

SCNNlA-6799 + UCCCAGAGAAGGUGUCAUCUCUG 23 10648

SCNNlA-6800 + UUCCCAGAGAAGGUGUCAUCUCUG 24 10649

SCNNlA-6801 + GACAGCGAAGGACAGAGAGAU 21 10650

SCNNlA-6802 + GGACAGCGAAGGACAGAGAGAU 22 10651

SCNNlA-6803 + GGGACAGCGAAGGACAGAGAGAU 23 10652

SCNNlA-6804 + AGGGACAGCGAAGGACAGAGAGAU 24 10653

SCNNlA-6805 + GCUCCCGAGGGCAGGUGAACU 21 10654

SCNNlA-6806 + GGCUCCCGAGGGCAGGUGAACU 22 10655

SCNNlA-6807 + GGGCUCCCGAGGGCAGGUGAACU 23 10656

SCNNlA-6808 + AGGGCUCCCGAGGGCAGGUGAACU 24 10657

SCNNlA-6809 + GAAAAG G C AG U AC U CC AG G C U 21 10658

SCNNlA-6810 + AGAAAAGGCAGUACUCCAGGCU 22 10659

SCNNlA-6811 + GAGAAAAGGCAGUACUCCAGGCU 23 10660

SCNNlA-6812 + AGAGAAAAGGCAGUACUCCAGGCU 24 10661

SCNNlA-6813 + CCCUGAUAGGGCCACCUU 18 10662

SCNNlA-6814 + UCCCUGAUAGGGCCACCUU 19 10663

SCNNlA-6815 + UUCCCUGAUAGGGCCACCUU 20 10664

SCNNlA-6816 - UGGAGAAAAUAUAGCCCAUCA 21 10665

SCNNlA-6817 - UUGGAGAAAAUAUAGCCCAUCA 22 10666

SCNNlA-6818 - UUUGGAGAAAAUAUAGCCCAUCA 23 10667

SCNNlA-6819 - UUUUGGAGAAAAUAUAGCCCAUCA 24 10668

1373

5535.1 SCNNlA-6820 - CCUGCAGUCCUGGGGCAGAGA 21 10669

SCNNlA-6821 - CCCUGCAGUCCUGGGGCAGAGA 22 10670

SCNNlA-6822 - GCCCUGCAGUCCUGGGGCAGAGA 23 10671

SCNNlA-6823 - AGCCCUGCAGUCCUGGGGCAGAGA 24 10672

SCNNlA-6824 - ACAGAAGGCAGAUAGAGA 18 10673

SCNNlA-6825 - AACAGAAGGCAGAUAGAGA 19 10674

SCNNlA-6088 - AAACAGAAGGCAGAUAGAGA 20 9937

SCNNlA-6826 - G A A AC AG AAGGCAGAUAGAGA 21 10675

SCNNlA-6827 - AGAAACAGAAGGCAGAUAGAGA 22 10676

SCNNlA-6828 - GAGAAACAGAAGGCAGAUAGAGA 23 10677

SCNNlA-6829 - AGAGAAACAGAAGGCAGAUAGAGA 24 10678

SCNNlA-1437 - CAUGGCCAGGGGCAGCCUCAC 21 5286

SCNNlA-1438 - GCAUGGCCAGGGGCAGCCUCAC 22 5287

SCNNlA-1439 - GGCAUGGCCAGGGGCAGCCUCAC 23 5288

SCNNlA-1440 - GGGCAUGGCCAGGGGCAGCCUCAC 24 5289

SCNNlA-6830 - AGGACCUGGCUCAAGGGAGAC 21 10679

SCNNlA-6831 - AAGGACCUGGCUCAAGGGAGAC 22 10680

SCNNlA-6832 - UAAGGACCUGGCUCAAGGGAGAC 23 10681

SCNNlA-6833 - GUAAGGACCUGGCUCAAGGGAGAC 24 10682

SCNNlA-6834 - AGGCUGGAGCUGAGGGCC 18 10683

SCNNlA-6835 - GAGGCUGGAGCUGAGGGCC 19 10684

SCNNlA-6836 - AGAGGCUGGAGCUGAGGGCC 20 10685

SCNNlA-6837 - CAGAGGCUGGAGCUGAGGGCC 21 10686

SCNNlA-6838 - CCAGAGGCUGGAGCUGAGGGCC 22 10687

SCNNlA-6839 - GCCAGAGGCUGGAGCUGAGGGCC 23 10688

SCNNlA-6840 - GGCCAGAGGCUGGAGCUGAGGGCC 24 10689

SCNNlA-1441 - GGGCAGCCUCACUCGGGUUCC 21 5290

SCNNlA-1442 - GGGGCAGCCUCACUCGGGUUCC 22 5291

SCNNlA-1443 - AGGGGCAGCCUCACUCGGGUUCC 23 5292

SCNNlA-1444 - CAGGGGCAGCCUCACUCGGGUUCC 24 5293

SCNNlA-6841 - UGGGUUGUGUGGGUGGCUCUC 21 10690

SCNNlA-6842 - CUGGGUUGUGUGGGUGGCUCUC 22 10691

SCNNlA-6843 - CCUGGGUUGUGUGGGUGGCUCUC 23 10692

SCNNlA-6844 - GCCUGGGUUGUGUGGGUGGCUCUC 24

10693

SCNNlA-6845 - CUUCUCUGGGAAGGCUUC 18 10694

SCNNlA-6846 - CCUUCUCUGGGAAGGCUUC 19 10695

SCNNlA-6847 - ACCUUCUCUGGGAAGGCUUC 20 10696

SCNNlA-6848 - CACCUUCUCUGGGAAGGCUUC 21 10697

SCNNlA-6849 - ACACCUUCUCUGGGAAGGCUUC 22 10698

SCNNlA-6850 - GACACCUUCUCUGGGAAGGCUUC 23 10699

SCNNlA-6851 - UGACACCUUCUCUGGGAAGGCUUC 24 10700

1374

5535.1 SCNNlA-6852 - AGGAGUGGGAGAAUGUGGGCG 21 10701

SCNNlA-6853 - GAGGAGUGGGAGAAUGUGGGCG 22 10702

SCNNlA-6854 - GGAGGAGUGGGAGAAUGUGGGCG 23 10703

SCNNlA-6855 - GGGAGGAGUGGGAGAAUGUGGGCG 24

10704

SCNNlA-6856 - GGGGGAGAGGAAGAGAGG 18 10705

SCNNlA-6857 - GGGGGGAGAGGAAGAGAGG 19 10706

SCNNlA-6858 - GGGGGGGAGAGGAAGAGAGG 20 10707

SCNNlA-6859 - AGGGGGGGAGAGGAAGAGAGG 21 10708

SCNNlA-6860 - AAGGGGGGGAGAGGAAGAGAGG 22 10709

SCNNlA-6861 - CAAGGGGGGGAGAGGAAGAGAGG 23 10710

SCNNlA-6862 - GCAAGGGGGGGAGAGGAAGAGAGG 24

10711

SCNNlA-6863 - AAGGUGGAGGAGGGAGGG 18 10712

SCNNlA-6864 - AAAGGUGGAGGAGGGAGGG 19 10713

SCNNlA-5911 - GAAAGGUGGAGGAGGGAGGG 20 9760

SCNNlA-6865 - GGAAAGGUGGAGGAGGGAGGG 21 10714

SCNNlA-6866 - AGGAAAGGUGGAGGAGGGAGGG 22 10715

SCNNlA-6867 - CAGGAAAGGUGGAGGAGGGAGGG 23 10716

SCNNlA-6868 - CCAGGAAAGGUGGAGGAGGGAGGG 24

10717

SCNNlA-6869 - GAAAACUGAUUUAUCCUUGGG 21 10718

SCNNlA-6870 - AGAAAACUGAUUUAUCCUUGGG 22 10719

SCNNlA-6871 - CAGAAAACUGAUUUAUCCUUGGG 23 10720

SCNNlA-6872 - UCAGAAAACUGAUUUAUCCUUGGG 24 10721

SCNNlA-6873 - GGAGGGAGGGAGGAGUGG 18 10722

SCNNlA-6874 - AGGAGGGAGGGAGGAGUGG 19 10723

SCNNlA-6875 - GAGGAGGGAGGGAGGAGUGG 20 10724

SCNNlA-6876 - GGAGGAGGGAGGGAGGAGUGG 21 10725

SCNNlA-6877 - UGGAGGAGGGAGGGAGGAGUGG 22 10726

SCNNlA-6878 - GUGGAGGAGGGAGGGAGGAGUGG 23 10727

SCNNlA-6879 - GGUGGAGGAGGGAGGGAGGAGUGG 24

10728

SCNNlA-6880 - UUCCCUGCCUCUUCCUGGGCU 21 10729

SCNNlA-6881 - UUUCCCUGCCUCUUCCUGGGCU 22 10730

SCNNlA-6882 - CUUUCCCUGCCUCUUCCUGGGCU 23 10731

SCNNlA-6883 - GCUUUCCCUGCCUCUUCCUGGGCU 24 10732

SCNNlA-6884 - UUGCCCUCCUAGCUGUGGGCU 21 10733

SCNNlA-6885 - GUUGCCCUCCUAGCUGUGGGCU 22 10734

SCNNlA-6886 - UGUUGCCCUCCUAGCUGUGGGCU 23 10735

SCNNlA-6887 - GUGUUGCCCUCCUAGCUGUGGGCU 24 10736

SCNNlA-6888 - CAG AGG AGG AGG AG AAU U 18 10737

1375

5535.1 SCNNlA-6889 - CCAGAGGAGGAGGAGAAUU 19 10738

SCNNlA-6890 - CCCAGAGGAGGAGGAGAAUU 20 10739

SCNNlA-6891 - CCCCAGAGGAGGAGGAGAAUU 21 10740

SCNNlA-6892 - GCCCCAGAGGAGGAGGAGAAUU 22 10741

SCNNlA-6893 - AGCCCCAGAGGAGGAGGAGAAUU 23 10742

SCNNlA-6894 - UAGCCCCAGAGGAGGAGGAGAAUU 24 10743

Table 47D provides exemplary targeting domains for knocking down the SCNNIA gene selected according to the fourth tier parameters. The targeting domains bind within 500 bp (e.g., upstream or downstream) of a transcription start site (TSS), and PAM is NNGRRV. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. Aureus eiCas9 molecule or eiCas9 fusion protein (e.g., an eiCas9 fused to a transcription repressor domain) to alter the SCNNIA gene (e.g., reduce or eliminate SCNNIA gene expression, SCNNIA protein function, or the level of SCNNIA protein). One or more gRNA may be used to target an eiCas9 to the promoter region of the SCNNIA gene.

Table 47D

1376

5535.1 SCNNlA-6913 + GGGGGGCAGUGGUGGGGGCAAA 22 10762

SCNNlA-6914 + UGGGGGGCAGUGGUGGGGGCAAA 23 10763

SCNNlA-6915 + GUGGGGGGCAGUGGUGGGGGCAAA 24

10764

SCNNlA-6916 + AGGACAGGAGGGCAGAAA 18 10765

SCNNlA-6917 + GAGGACAGGAGGGCAGAAA 19 10766

SCNNlA-6918 + GGAGGACAGGAGGGCAGAAA 20 10767

SCNNlA-6919 + GGGAGGACAGGAGGGCAGAAA 21 10768

SCNNlA-6920 + CGGGAGGACAGGAGGGCAGAAA 22 10769

SCNNlA-6921 + CCGGGAGGACAGGAGGGCAGAAA 23 10770

SCNNlA-6922 + ACCGGGAGGACAGGAGGGCAGAAA 24 10771

SCNNlA-6923 + CUCUUGCGACUUCUUAAA 18 10772

SCNNlA-6924 + UCUCUUGCGACUUCUUAAA 19 10773

SCNNlA-6925 + GUCUCUUGCGACUUCUUAAA 20 10774

SCNNlA-6926 + AGUCUCUUGCGACUUCUUAAA 21 10775

SCNNlA-6927 + CAGUCUCUUGCGACUUCUUAAA 22 10776

SCNNlA-6928 + GCAGUCUCUUGCGACUUCUUAAA 23 10777

SCNNlA-6929 + GGCAGUCUCUUGCGACUUCUUAAA 24 10778

SCNNlA-6930 + UAAAAGAUUGUCUUUAAA 18 10779

SCNNlA-6931 + UUAAAAGAUUGUCUUUAAA 19 10780

SCNNlA-6932 + UUUAAAAGAUUGUCUUUAAA 20 10781

SCNNlA-6933 + CUUUAAAAGAUUGUCUUUAAA 21 10782

SCNNlA-6934 + ACUUUAAAAGAUUGUCUUUAAA 22 10783

SCNNlA-6935 + CACU U U AAAAG AU UG U CU U U AAA 23 10784

SCNNlA-6936 + ACACUUUAAAAGAUUGUCUUUAAA 24 10785

SCNNlA-6937 + GCAGAAAGAGGGAGACAA 18 10786

SCNNlA-6938 + GGCAGAAAGAGGGAGACAA 19 10787

SCNNlA-6939 + GGGCAGAAAGAGGGAGACAA 20 10788

SCNNlA-6940 + AGGGCAGAAAGAGGGAGACAA 21 10789

SCNNlA-6941 + GAGGGCAGAAAGAGGGAGACAA 22 10790

SCNNlA-6942 + GGAGGGCAGAAAGAGGGAGACAA 23 10791

SCNNlA-6943 + AGGAGGGCAGAAAGAGGGAGACAA 24 10792

SCNNlA-6944 + AGAAGGAGCCAGCACCAA 18 10793

SCNNlA-6945 + UAGAAGGAGCCAGCACCAA 19 10794

SCNNlA-5518 + AUAGAAGGAGCCAGCACCAA 20 9367

SCNNlA-6946 + AAUAGAAGGAGCCAGCACCAA 21 10795

SCNNlA-6947 + AAAUAGAAGGAGCCAGCACCAA 22 10796

SCNNlA-6948 + C A A A UAGAAGGAGCCAGCACCAA 23 10797

SCNNlA-6949 + GCAAAUAGAAGGAGCCAGCACCAA 24 10798

SCNNlA-6950 + GAGCUAGAGGCUCAGCAA 18 10799

SCNNlA-6951 + GGAGCUAGAGGCUCAGCAA 19 10800

SCNNlA-6952 + AGGAGCUAGAGGCUCAGCAA 20 10801

1377

5535.1 SCNNlA-6953 + CAGGAGCUAGAGGCUCAGCAA 21 10802

SCNNlA-6954 + CCAGGAGCUAGAGGCUCAGCAA 22 10803

SCNNlA-6955 + UCCAGGAGCUAGAGGCUCAGCAA 23 10804

SCNNlA-6956 + UUCCAGGAGCUAGAGGCUCAGCAA 24 10805

SCNNlA-6957 + CUCCAGGAAGGAGAGCAA 18 10806

SCNNlA-6958 + UCUCCAGGAAGGAGAGCAA 19 10807

SCNNlA-5168 + GUCUCCAGGAAGGAGAGCAA 20 9017

SCNNlA-6959 + UGUCUCCAGGAAGGAGAGCAA 21 10808

SCNNlA-6960 + CUGUCUCCAGGAAGGAGAGCAA 22 10809

SCNNlA-6961 + UCUGUCUCCAGGAAGGAGAGCAA 23 10810

SCNNlA-6962 + GUCUGUCUCCAGGAAGGAGAGCAA 24 10811

SCNNlA-6963 + AGUUUAGCAGG C A A AG A A 18 10812

SCNNlA-6964 + GAG U U U AGCAGG CAAAG AA 19 10813

SCNNlA-6965 + GGAGUUUAGCAGGCAAAGAA 20 10814

SCNNlA-6966 + AGGAGUUUAGCAGGCAAAGAA 21 10815

SCNNlA-6967 + AAGGAGUUUAGCAGGCAAAGAA 22 10816

SCNNlA-6968 + CAAGGAGUUUAGCAGGCAAAGAA 23 10817

SCNNlA-6969 + G CAAG GAG U U U AG C AG G C AAAG AA 24 10818

SCNNlA-6970 + CUCAGGCCCUGCAGAGAA 18 10819

SCNNlA-6971 + CCUCAGGCCCUGCAGAGAA 19 10820

SCNNlA-6972 + CCCUCAGGCCCUGCAGAGAA 20 10821

SCNNlA-6973 + ACCCUCAGGCCCUGCAGAGAA 21 10822

SCNNlA-6974 + CACCCUCAGGCCCUGCAGAGAA 22 10823

SCNNlA-6975 + UCACCCUCAGGCCCUGCAGAGAA 23 10824

SCNNlA-6976 + CUCACCCUCAGGCCCUGCAGAGAA 24 10825

SCNNlA-6977 + GAGGGCCUGGGUGGGGAA 18 10826

SCNNlA-6978 + AGAGGGCCUGGGUGGGGAA 19 10827

SCNNlA-6979 + GAGAGGGCCUGGGUGGGGAA 20 10828

SCNNlA-6980 + UGAGAGGGCCUGGGUGGGGAA 21 10829

SCNNlA-6981 + CUGAGAGGGCCUGGGUGGGGAA 22 10830

SCNNlA-6982 + GCUGAGAGGGCCUGGGUGGGGAA 23 10831

SCNNlA-6983 + GGCUGAGAGGGCCUGGGUGGGGAA 24

10832

SCNNlA-6984 + AUGUGGCCAGCGCUGGAA 18 10833

SCNNlA-6985 + GAUGUGGCCAGCGCUGGAA 19 10834

SCNNlA-5174 + GGAUGUGGCCAGCGCUGGAA 20 9023

SCNNlA-6986 + AGGAUGUGGCCAGCGCUGGAA 21 10835

SCNNlA-6987 + GAGGAUGUGGCCAGCGCUGGAA 22 10836

SCNNlA-6988 + GGAGGAUGUGGCCAGCGCUGGAA 23 10837

SCNNlA-6989 + GGGAGGAUGUGGCCAGCGCUGGAA 24 10838

SCNNlA-6990 + CUCCCGAGGGCAGGUGAA 18 10839

SCNNlA-6991 + GCUCCCGAGGGCAGGUGAA 19 10840

1378

5535.1 SCNNlA-6992 + GGCUCCCGAGGGCAGGUGAA 20 10841

SCNNlA-6993 + GGGCUCCCGAGGGCAGGUGAA 21 10842

SCNNlA-6994 + AGGGCUCCCGAGGGCAGGUGAA 22 10843

SCNNlA-6995 + GAGGGCUCCCGAGGGCAGGUGAA 23 10844

SCNNlA-6996 + GGAGGGCUCCCGAGGGCAGGUGAA 24 10845

SCNNlA-6997 + CUCCUCCCCGCUCACUAA 18 10846

SCNNlA-6998 + UCUCCUCCCCGCUCACUAA 19 10847

SCNNlA-6999 + GUCUCCUCCCCGCUCACUAA 20 10848

SCNNlA-7000 + GGUCUCCUCCCCGCUCACUAA 21 10849

SCNNlA-7001 + AGGUCUCCUCCCCGCUCACUAA 22 10850

SCNNlA-7002 + CAGGUCUCCUCCCCGCUCACUAA 23 10851

SCNNlA-7003 + GCAGGUCUCCUCCCCGCUCACUAA 24 10852

SCNNlA-7004 + AGCUAGGAGGGCAACACA 18 10853

SCNNlA-7005 + CAGCUAGGAGGGCAACACA 19 10854

SCNNlA-5527 + ACAGCUAGGAGGGCAACACA 20 9376

SCNNlA-7006 + CACAGCUAGGAGGGCAACACA 21 10855

SCNNlA-7007 + CCACAGCUAGGAGGGCAACACA 22 10856

SCNNlA-7008 + CCCA CAGCUAGGAGGGCAACACA 23 10857

SCNNlA-7009 + GCCCACAGCUAGGAGGGCAACACA 24 10858

SCNNlA-7010 + CCUGAGCAUUGAUACACA 18 10859

SCNNlA-7011 + GCCUGAGCAUUGAUACACA 19 10860

SCNNlA-7012 + AGCCUGAGCAUUGAUACACA 20 10861

SCNNlA-7013 + CAGCCUGAGCAUUGAUACACA 21 10862

SCNNlA-7014 + CCAGCCUGAGCAUUGAUACACA 22 10863

SCNNlA-7015 + CCCAGCCUGAGCAUUGAUACACA 23 10864

SCNNlA-7016 + GCCCAGCCUGAGCAUUGAUACACA 24 10865

SCNNlA-7017 + GCCUCCCUCACUCCCACA 18 10866

SCNNlA-7018 + GGCCUCCCUCACUCCCACA 19 10867

SCNNlA-7019 + AGGCCUCCCUCACUCCCACA 20 10868

SCNNlA-7020 + AAGGCCUCCCUCACUCCCACA 21 10869

SCNNlA-7021 + GAAGGCCUCCCUCACUCCCACA 22 10870

SCNNlA-7022 + GGAAGGCCUCCCUCACUCCCACA 23 10871

SCNNlA-7023 + GGGAAGGCCUCCCUCACUCCCACA 24 10872

SCNNlA-7024 + GAGGGACAGCGAAGGACA 18 10873

SCNNlA-7025 + AGAGGGACAGCGAAGGACA 19 10874

SCNNlA-7026 + GAGAGGGACAGCGAAGGACA 20 10875

SCNNlA-7027 + AGAGAGGGACAGCGAAGGACA 21 10876

SCNNlA-7028 + UAGAGAGGGACAGCGAAGGACA 22 10877

SCNNlA-7029 + AUAGAGAGGGACAGCGAAGGACA 23 10878

SCNNlA-7030 + AAUAGAGAGGGACAGCGAAGGACA 24 10879

SCNNlA-7031 + AGACAAUAGAGAGGGACA 18 10880

SCNNlA-7032 + GAGACAAUAGAGAGGGACA 19 10881

1379

5535.1 SCNNlA-7033 + GGAGACAAUAGAGAGGGACA 20 10882

SCNNlA-7034 + GGGAGACAAUAGAGAGGGACA 21 10883

SCNNlA-7035 + AGGGAGACAAUAGAGAGGGACA 22 10884

SCNNlA-7036 + GAGGGAGACAAUAGAGAGGGACA 23 10885

SCNNlA-7037 + AGAGGGAGACAAUAGAGAGGGACA 24 10886

SCNNlA-7038 + UUGAGCCAGGUCCUUACA 18 10887

SCNNlA-7039 + CUUGAGCCAGGUCCUUACA 19 10888

SCNNlA-7040 + CCUUGAGCCAGGUCCUUACA 20 10889

SCNNlA-7041 + CCCUUGAGCCAGGUCCUUACA 21 10890

SCNNlA-7042 + UCCCUUGAGCCAGGUCCUUACA 22 10891

SCNNlA-7043 + CUCCCUUGAGCCAGGUCCUUACA 23 10892

SCNNlA-7044 + UCUCCCUUGAGCCAGGUCCUUACA 24 10893

SCNNlA-7045 + UAGAAGGAGCCAGCACCA 18 10894

SCNNlA-7046 + AUAGAAGGAGCCAGCACCA 19 10895

SCNNlA-7047 + AAUAGAAGGAGCCAGCACCA 20 10896

SCNNlA-7048 + AAAUAGAAGGAGCCAGCACCA 21 10897

SCNNlA-7049 + CAAAUAGAAGGAGCCAGCACCA 22 10898

SCNNlA-7050 + GCAAAUAGAAGGAGCCAGCACCA 23 10899

SCNNlA-7051 + GGCAAAUAGAAGGAGCCAGCACCA 24 10900

SCNNlA-7052 + GCUUCCUCACGGGCCCCA 18 10901

SCNNlA-7053 + CGCUUCCUCACGGGCCCCA 19 10902

SCNNlA-7054 + CCGCUUCCUCACGGGCCCCA 20 10903

SCNNlA-7055 + GCCGCUUCCUCACGGGCCCCA 21 10904

SCNNlA-7056 + UGCCGCUUCCUCACGGGCCCCA 22 10905

SCNNlA-7057 + CUGCCGCUUCCUCACGGGCCCCA 23 10906

SCNNlA-7058 + GCUGCCGCUUCCUCACGGGCCCCA 24 10907

SCNNlA-7059 + ACUCAGGAAGCCUUCCCA 18 10908

SCNNlA-7060 + GACUCAGGAAGCCUUCCCA 19 10909

SCNNlA-7061 + AGACUCAGGAAGCCUUCCCA 20 10910

SCNNlA-7062 + GAGACUCAGGAAGCCUUCCCA 21 10911

SCNNlA-7063 + GGAGACUCAGGAAGCCUUCCCA 22 10912

SCNNlA-7064 + AGGAGACUCAGGAAGCCUUCCCA 23 10913

SCNNlA-7065 + CAGGAGACUCAGGAAGCCUUCCCA 24 10914

SCNNlA-7066 + UCUCCAGGAAGGAGAGCA 18 10915

SCNNlA-7067 + GUCUCCAGGAAGGAGAGCA 19 10916

SCNNlA-5533 + UGUCUCCAGGAAGGAGAGCA 20 9382

SCNNlA-7068 + CUGUCUCCAGGAAGGAGAGCA 21 10917

SCNNlA-7069 + UCUGUCUCCAGGAAGGAGAGCA 22 10918

SCNNlA-7070 + GUCUGUCUCCAGGAAGGAGAGCA 23 10919

SCNNlA-7071 + AGUCUGUCUCCAGGAAGGAGAGCA 24 10920

SCNNlA-7072 + AGUGCCAAGUGGUGAGCA 18 10921

SCNNlA-7073 + GAGUGCCAAGUGGUGAGCA 19 10922

1380

5535.1 SCNNlA-5179 + GGAGUGCCAAGUGGUGAGCA 20 9028

SCNNlA-7074 + UGGAGUGCCAAGUGGUGAGCA 21 10923

SCNNlA-7075 + GUGGAGUGCCAAGUGGUGAGCA 22 10924

SCNNlA-7076 + AGUGGAGUGCCAAGUGGUGAGCA 23 10925

SCNNlA-7077 + GAGUGGAGUGCCAAGUGGUGAGCA 24 10926

SCNNlA-7078 + U U U AG ACGCAG ACAGG CA 18 10927

SCNNlA-7079 + CUUUAGACGCAGACAGGCA 19 10928

SCNNlA-5181 + GCUUUAGACGCAGACAGGCA 20 9030

SCNNlA-7080 + GGCUUUAGACGCAGACAGGCA 21 10929

SCNNlA-7081 + GGGCUUUAGACGCAGACAGGCA 22 10930

SCNNlA-7082 + GGGGCUUUAGACGCAGACAGGCA 23 10931

SCNNlA-7083 + AGGGGCUUUAGACGCAGACAGGCA 24 10932

SCNNlA-7084 + AGGCAGGGAAAGCAGGCA 18 10933

SCNNlA-7085 + G AG G C AGG G AAAG CAG G CA 19 10934

SCNNlA-7086 + AG AG G C AGG G AAAG CAG G C A 20 10935

SCNNlA-7087 + AAGAGGCAGGGAAAGCAGGCA 21 10936

SCNNlA-7088 + GAAGAGGCAG G G A A AG C AG G C A 22 10937

SCNNlA-7089 + GGAAGAGGCAGGGAAAGCAGGCA 23 10938

SCNNlA-7090 + AGGAAGAGGCAGGGAAAGCAGGCA 24 10939

SCNNlA-7091 + CAAGGAGUUUAGCAGGCA 18 10940

SCNNlA-7092 + GCAAGGAGUUUAGCAGGCA 19 10941

SCNNlA-7093 + AG C A AG GAG UUUAGCAGGCA 20 10942

SCNNlA-7094 + AAGCAAGGAGUUUAGCAGGCA 21 10943

SCNNlA-7095 + C A AG C A AG GAG UUUAGCAGGCA 22 10944

SCNNlA-7096 + ACAAG CAAG G AG U U U AG CAG G C A 23 10945

SCNNlA-7097 + GACAAGCAAGGAGUUUAGCAGGCA 24 10946

SCNNlA-7098 + GGAGCCCAGGAAGAGGCA 18 10947

SCNNlA-7099 + CGGAGCCCAGGAAGAGGCA 19 10948

SCNNlA-5535 + CCGGAGCCCAGGAAGAGGCA 20 9384

SCNNlA-7100 + CCCGGAGCCCAGGAAGAGGCA 21 10949

SCNNlA-7101 + ACCCGGAGCCCAGGAAGAGGCA 22 10950

SCNNlA-7102 + GACCCGGAGCCCAGGAAGAGGCA 23 10951

SCNNlA-7103 + AGACCCGGAGCCCAGGAAGAGGCA 24 10952

SCNNlA-7104 + CAGGCCCUGCACGCGGCA 18 10953

SCNNlA-7105 + CCAGGCCCUGCACGCGGCA 19 10954

SCNNlA-5536 + CCCAGGCCCUGCACGCGGCA 20 9385

SCNNlA-7106 + ACCCAGGCCCUGCACGCGGCA 21 10955

SCNNlA-7107 + AACCCAGGCCCUGCACGCGGCA 22 10956

SCNNlA-7108 + CAACCCAGGCCCUGCACGCGGCA 23 10957

SCNNlA-7109 + ACAACCCAGGCCCUGCACGCGGCA 24 10958

SCNNlA-7110 + UCACCCUCAGGCCCUGCA 18 10959

SCNNlA-7111 + CUCACCCUCAGGCCCUGCA 19 10960

1381

5535.1 SCNNlA-7112 + CCUCACCCUCAGGCCCUGCA 20 10961

SCNNlA-7113 + GCCUCACCCUCAGGCCCUGCA 21 10962

SCNNlA-7114 + AGCCUCACCCUCAGGCCCUGCA 22 10963

SCNNlA-7115 + CAGCCUCACCCUCAGGCCCUGCA 23 10964

SCNNlA-7116 + UCAGCCUCACCCUCAGGCCCUGCA 24 10965

SCNNlA-7117 + GCAGGCACUGAAGGUGCA 18 10966

SCNNlA-7118 + AG C AGG CAC U G AAG G U G C A 19 10967

SCNNlA-5539 + AAGCAGGCACUGAAGGUGCA 20 9388

SCNNlA-7119 + AAAG C AGG CAC U G AAG G U G C A 21 10968

SCNNlA-7120 + G A A AG CAGGCACUGAAGGUGCA 22 10969

SCNNlA-7121 + GGAAAGCAGGCACUGAAGGUGCA 23 10970

SCNNlA-7122 + GGGAAAGCAGGCACUGAAGGUGCA 24 10971

SCNNlA-7123 + CUUCCUGAGACAGACUCA 18 10972

SCNNlA-7124 + ACUUCCUGAGACAGACUCA 19 10973

SCNNlA-6083 + UACUUCCUGAGACAGACUCA 20 9932

SCNNlA-7125 + UUACUUCCUGAGACAGACUCA 21 10974

SCNNlA-7126 + UUUACUUCCUGAGACAGACUCA 22 10975

SCNNlA-7127 + AUUUACUUCCUGAGACAGACUCA 23 10976

SCNNlA-7128 + CAUUUACUUCCUGAGACAGACUCA 24 10977

SCNNlA-7129 + GACAGGAGGGCAGAAAGA 18 10978

SCNNlA-7130 + GGACAGGAGGGCAGAAAGA 19 10979

SCNNlA-6085 + AGGACAGGAGGGCAGAAAGA 20 9934

SCNNlA-7131 + GAGGACAGGAGGGCAGAAAGA 21 10980

SCNNlA-7132 + GGAGGACAGGAGGGCAGAAAGA 22 10981

SCNNlA-7133 + GGGAGGACAGGAGGGCAGAAAGA 23 10982

SCNNlA-7134 + CGGGAGGACAGGAGGGCAGAAAGA 24 10983

SCNNlA-7135 + CAGGCCCUGCAGAGAAGA 18 10984

SCNNlA-7136 + UCAGGCCCUGCAGAGAAGA 19 10985

SCNNlA-7137 + CUCAGGCCCUGCAGAGAAGA 20 10986

SCNNlA-7138 + CCUCAGGCCCUGCAGAGAAGA 21 10987

SCNNlA-7139 + CCCUCAGGCCCUGCAGAGAAGA 22 10988

SCNNlA-7140 + ACCCUCAGGCCCUGCAGAGAAGA 23 10989

SCNNlA-7141 + CACCCUCAGGCCCUGCAGAGAAGA 24 10990

SCNNlA-7142 + GGAGGACAGGAGGGCAGA 18 10991

SCNNlA-7143 + GGGAGGACAGGAGGGCAGA 19 10992

SCNNlA-7144 + CGGGAGGACAGGAGGGCAGA 20 10993

SCNNlA-7145 + CCGGGAGGACAGGAGGGCAGA 21 10994

SCNNlA-7146 + ACCGGGAGGACAGGAGGGCAGA 22 10995

SCNNlA-7147 + AACCGGGAGGACAGGAGGGCAGA 23 10996

SCNNlA-7148 + GAACCGGGAGGACAGGAGGGCAGA 24 10997

SCNNlA-7149 + CAGCGAAGGACAGAGAGA 18 10998

SCNNlA-7150 + ACAGCGAAGGACAGAGAGA 19 10999

1382

5535.1 SCNNlA-7151 + GACAGCGAAGGACAGAGAGA 20 11000

SCNNlA-7152 + GGACAGCGAAGGACAGAGAGA 21 11001

SCNNlA-7153 + GGGACAGCGAAGGACAGAGAGA 22 11002

SCNNlA-7154 + AGGGACAGCGAAGGACAGAGAGA 23 11003

SCNNlA-7155 + GAGGGACAGCGAAGGACAGAGAGA 24 11004

SCNNlA-7156 + GUGGUGAGCAAGGAGAGA 18 11005

SCNNlA-7157 + AGUGGUGAGCAAGGAGAGA 19 11006

SCNNlA-7158 + AAGUGGUGAGCAAGGAGAGA 20 11007

SCNNlA-7159 + CAAGUGGUGAGCAAGGAGAGA 21 11008

SCNNlA-7160 + CCAAGUGGUGAGCAAGGAGAGA 22 11009

SCNNlA-7161 + GCCAAGUGGUGAGCAAGGAGAGA 23 11010

SCNNlA-7162 + UGCCAAGUGGUGAGCAAGGAGAGA 24 11011

SCNNlA-7163 + GAGGGCAACACAAGGAGA 18 11012

SCNNlA-7164 + GGAGGGCAACACAAGGAGA 19 11013

SCNNlA-6089 + AGGAGGGCAACACAAGGAGA 20 9938

SCNNlA-7165 + UAGGAGGGCAACACAAGGAGA 21 11014

SCNNlA-7166 + CUAGGAGGGCAACACAAGGAGA 22 11015

SCNNlA-7167 + GCUAGGAGGGCAACACAAGGAGA 23 11016

SCNNlA-7168 + AGCUAGGAGGGCAACACAAGGAGA 24 11017

SCNNlA-7169 + AAGUGGUGAGCAAGGAGA 18 11018

SCNNlA-7170 + CAAGUGGUGAGCAAGGAGA 19 11019

SCNNlA-7171 + CCAAGUGGUGAGCAAGGAGA 20 11020

SCNNlA-7172 + GCCAAGUGGUGAGCAAGGAGA 21 11021

SCNNlA-7173 + UGCCAAGUGGUGAGCAAGGAGA 22 11022

SCNNlA-7174 + GUGCCAAGUGGUGAGCAAGGAGA 23 11023

SCNNlA-7175 + AGUGCCAAGUGGUGAGCAAGGAGA 24 11024

SCNNlA-7176 + GUGGUGGGGGCAAAUAGA 18 11025

SCNNlA-7177 + AGUGGUGGGGGCAAAUAGA 19 11026

SCNNlA-6091 + CAGUGGUGGGGGCAAAUAGA 20 9940

SCNNlA-7178 + GCAGUGGUGGGGGCAAAUAGA 21 11027

SCNNlA-7179 + GGCAGUGGUGGGGGCAAAUAGA 22 11028

SCNNlA-7180 + GGGCAGUGGUGGGGGCAAAUAGA 23 11029

SCNNlA-7181 + GGGGCAGUGGUGGGGGCAAAUAGA 24

11030

SCNNlA-7182 + AAAGAGGGAGACAAUAGA 18 11031

SCNNlA-7183 + GAAAGAGGGAGACAAUAGA 19 11032

SCNNlA-7184 + AGAAAGAGGGAGACAAUAGA 20 11033

SCNNlA-7185 + CAGAAAGAGGGAGACAAUAGA 21 11034

SCNNlA-7186 + GCAGAAAGAGGGAGACAAUAGA 22 11035

SCNNlA-7187 + GGCAGAAAGAGGGAGACAAUAGA 23 11036

SCNNlA-7188 + GGGCAGAAAGAGGGAGACAAUAGA 24 11037

SCNNlA-1445 + AUCACCCCUGGAACCCGA 18 5294

1383

5535.1 SCNNlA-1446 + CAUCACCCCUGGAACCCGA 19 5295

SCNNlA-1447 + CCAUCACCCCUGGAACCCGA 20 5296

SCNNlA-1448 + CCCAUCACCCCUGGAACCCGA 21 5297

SCNNlA-1449 + UCCCAUCACCCCUGGAACCCGA 22 5298

SCNNlA-1450 + CUCCCAUCACCCCUGGAACCCGA 23 5299

SCNNlA-1451 + UCUCCCAUCACCCCUGGAACCCGA 24 5300

SCNNlA-7189 + GAGCCGGGAGUUUUCCGA 18 11038

SCNNlA-7190 + AGAGCCGGGAGUUUUCCGA 19 11039

SCNNlA-5544 + CAGAGCCGGGAGUUUUCCGA 20 9393

SCNNlA-7191 + UCAGAGCCGGGAGUUUUCCGA 21 11040

SCNNlA-7192 + GUCAGAGCCGGGAGUUUUCCGA 22 11041

SCNNlA-7193 + AGUCAGAGCCGGGAGUUUUCCGA 23 11042

SCNNlA-7194 + GAGUCAGAGCCGGGAGUUUUCCGA 24 11043

SCNNlA-7195 + GGCCAGGGAUGGAAGCGA 18 11044

SCNNlA-7196 + CGGCCAGGGAUGGAAGCGA 19 11045

SCNNlA-7197 + CCGGCCAGGGAUGGAAGCGA 20 11046

SCNNlA-7198 + GCCGGCCAGGGAUGGAAGCGA 21 11047

SCNNlA-7199 + GGCCGGCCAGGGAUGGAAGCGA 22 11048

SCNNlA-7200 + UGGCCGGCCAGGGAUGGAAGCGA 23 11049

SCNNlA-7201 + CUGGCCGGCCAGGGAUGGAAGCGA 24 11050

SCNNlA-7202 + CCAAGUGGUGAGCAAGGA 18 11051

SCNNlA-7203 + G CCAAG U G G U G AG C AAG G A 19 11052

SCNNlA-7204 + UGCCAAGUGGUGAGCAAGGA 20 11053

SCNNlA-7205 + GUGCCAAGUGGUGAGCAAGGA 21 11054

SCNNlA-7206 + AGUGCCAAGUGGUGAGCAAGGA 22 11055

SCNNlA-7207 + GAGUGCCAAGUGGUGAGCAAGGA 23 11056

SCNNlA-7208 + GGAGUGCCAAGUGGUGAGCAAGGA 24 11057

SCNNlA-7209 + CGGGAGUUUUCCGAAGGA 18 11058

SCNNlA-7210 + CCGGGAGUUUUCCGAAGGA 19 11059

SCNNlA-5190 + GCCGGGAGUUUUCCGAAGGA 20 9039

SCNNlA-7211 + AGCCGGGAGUUUUCCGAAGGA 21 11060

SCNNlA-7212 + GAGCCGGGAGUUUUCCGAAGGA 22 11061

SCNNlA-7213 + AG AG CCGGG AG U U U UCCGAAGGA 23 11062

SCNNlA-7214 + CAGAGCCGGGAGUUUUCCGAAGGA 24 11063

SCNNlA-7215 + GAGAGGGACAGCGAAGGA 18 11064

SCNNlA-7216 + AGAGAGGGACAGCGAAGGA 19 11065

SCNNlA-7217 + UAGAGAGGGACAGCGAAGGA 20 11066

SCNNlA-7218 + AUAGAGAGGGACAGCGAAGGA 21 11067

SCNNlA-7219 + AAUAGAGAGGGACAGCGAAGGA 22 11068

SCNNlA-7220 + CAAUAGAGAGGGACAGCGAAGGA 23 11069

SCNNlA-7221 + ACAAUAGAGAGGGACAGCGAAGGA 24 11070

SCNNlA-7222 + GCAGCAAAAGGAUAAGGA 18 11071

1384

5535.1 SCNNlA-7223 + UGCAGCAAAAGGAUAAGGA 19 11072

SCNNlA-7224 + AUGCAGCAAAAGGAUAAGGA 20 11073

SCNNlA-7225 + A A U G C AG C A A A AG G A U A AG G A 21 11074

SCNNlA-7226 + UAAUGCAGCAAAAGGAUAAGGA 22 11075

SCNNlA-7227 + UUAAUGCAGCAAAAGGAUAAGGA 23 11076

SCNNlA-7228 + CUUAAUGCAGCAAAAGGAUAAGGA 24 11077

SCNNlA-7229 + GGGAGUCUGUCUCCAGGA 18 11078

SCNNlA-7230 + AGGGAGUCUGUCUCCAGGA 19 11079

SCNNlA-5546 + AAGGGAGUCUGUCUCCAGGA 20 9395

SCNNlA-7231 + AAAGGGAGUCUGUCUCCAGGA 21 11080

SCNNlA-7232 + CAAAGGGAGUCUGUCUCCAGGA 22 11081

SCNNlA-7233 + CCAAAGGGAGUCUGUCUCCAGGA 23 11082

SCNNlA-7234 + ACCAAAGGGAGUCUGUCUCCAGGA 24 11083

SCNNlA-7235 + GGUGGGGAACCGGGAGGA 18 11084

SCNNlA-7236 + GGGUGGGGAACCGGGAGGA 19 11085

SCNNlA-7237 + UGGGUGGGGAACCGGGAGGA 20 11086

SCNNlA-7238 + CUGGGUGGGGAACCGGGAGGA 21 11087

SCNNlA-7239 + CCUGGGUGGGGAACCGGGAGGA 22 11088

SCNNlA-7240 + GCCUGGGUGGGGAACCGGGAGGA 23 11089

SCNNlA-7241 + GGCCUGGGUGGGGAACCGGGAGGA 24 11090

SCNNlA-7242 + CCGCUGGCCGGCCAGGGA 18 11091

SCNNlA-7243 + CCCGCUGGCCGGCCAGGGA 19 11092

SCNNlA-5192 + GCCCGCUGGCCGGCCAGGGA 20 9041

SCNNlA-7244 + CGCCCGCUGGCCGGCCAGGGA 21 11093

SCNNlA-7245 + CCGCCCGCUGGCCGGCCAGGGA 22 11094

SCNNlA-7246 + CCCGCCCGCUGGCCGGCCAGGGA 23 11095

SCNNlA-7247 + GCCCGCCCGCUGGCCGGCCAGGGA 24 11096

SCNNlA-7248 + AGGACAGAGAGAUAGGGA 18 11097

SCNNlA-7249 + AAGGACAGAGAGAUAGGGA 19 11098

SCNNlA-5878 + GAAGGACAGAGAGAUAGGGA 20 9727

SCNNlA-7250 + CGAAGGACAGAGAGAUAGGGA 21 11099

SCNNlA-7251 + GCGAAGGACAGAGAGAUAGGGA 22 11100

SCNNlA-7252 + AGCGAAGGACAGAGAGAUAGGGA 23 11101

SCNNlA-7253 + CAGCGAAGGACAGAGAGAUAGGGA 24 11102

SCNNlA-7254 + AGACAGACUCAUGGGGGA 18 11103

SCNNlA-7255 + GAGACAGACUCAUGGGGGA 19 11104

SCNNlA-7256 + UGAGACAGACUCAUGGGGGA 20 11105

SCNNlA-7257 + CUGAGACAGACUCAUGGGGGA 21 11106

SCNNlA-7258 + CCUGAGACAGACUCAUGGGGGA 22 11107

SCNNlA-7259 + UCCUGAGACAGACUCAUGGGGGA 23 11108

SCNNlA-7260 + UUCCUGAGACAGACUCAUGGGGGA 24 11109

SCNNlA-7261 + GAUGUGGCCAGCGCUGGA 18 11110

1385

5535.1 SCNNlA-7262 + GGAUGUGGCCAGCGCUGGA 19 11111

SCNNlA-7263 + AGGAUGUGGCCAGCGCUGGA 20 11112

SCNNlA-7264 + GAGGAUGUGGCCAGCGCUGGA 21 11113

SCNNlA-7265 + GGAGGAUGUGGCCAGCGCUGGA 22 11114

SCNNlA-7266 + GGGAGGAUGUGGCCAGCGCUGGA 23 11115

SCNNlA-7267 + AGGGAGGAUGUGGCCAGCGCUGGA 24 11116

SCNNlA-7268 + UCCCAGGUUGCGGCUGGA 18 11117

SCNNlA-7269 + CUCCCAGGUUGCGGCUGGA 19 11118

SCNNlA-7270 + ACUCCCAGGUUGCGGCUGGA 20 11119

SCNNlA-7271 + CACUCCCAGGUUGCGGCUGGA 21 11120

SCNNlA-7272 + CCACUCCCAGGUUGCGGCUGGA 22 11121

SCNNlA-7273 + CCCACUCCCAGGUUGCGGCUGGA 23 11122

SCNNlA-7274 + UCCCACUCCCAGGUUGCGGCUGGA 24 11123

SCNNlA-1465 + CAUGAGCCCCGGAGUGGA 18 5314

SCNNlA-1466 + UCAUGAGCCCCGGAGUGGA 19 5315

SCNNlA-1467 + UUCAUGAGCCCCGGAGUGGA 20 5316

SCNNlA-1468 + CUUCAUGAGCCCCGGAGUGGA 21 5317

SCNNlA-1469 + CCUUCAUGAGCCCCGGAGUGGA 22 5318

SCNNlA-1470 + CCCUUCAUGAGCCCCGGAGUGGA 23 5319

SCNNlA-1471 + CCCCUUCAUGAGCCCCGGAGUGGA 24 5320

SCNNlA-1472 + AUGAUACCUCCCCUUGGA 18 5321

SCNNlA-1473 + CAUGAUACCUCCCCUUGGA 19 5322

SCNNlA-399 + UCAUGAUACCUCCCCUUGGA 20 4248

SCNNlA-1474 + CUCAUGAUACCUCCCCUUGGA 21 5323

SCNNlA-1475 + GCUCAUGAUACCUCCCCUUGGA 22 5324

SCNNlA-1476 + UGCUCAUGAUACCUCCCCUUGGA 23 5325

SCNNlA-1477 + CUGCUCAUGAUACCUCCCCUUGGA 24 5326

SCNNlA-7275 + UCUCCUCUGCUUCCCUGA 18 11124

SCNNlA-7276 + CUCUCCUCUGCUUCCCUGA 19 11125

SCNNlA-7277 + CCUCUCCUCUGCUUCCCUGA 20 11126

SCNNlA-7278 + GCCUCUCCUCUGCUUCCCUGA 21 11127

SCNNlA-7279 + GGCCUCUCCUCUGCUUCCCUGA 22 11128

SCNNlA-7280 + CGGCCUCUCCUCUGCUUCCCUGA 23 11129

SCNNlA-7281 + ACGGCCUCUCCUCUGCUUCCCUGA 24 11130

SCNNlA-7282 + AGGGGCCAGCCAGGCUGA 18 11131

SCNNlA-7283 + AAGGGGCCAGCCAGGCUGA 19 11132

SCNNlA-7284 + GAAGGGGCCAGCCAGGCUGA 20 11133

SCNNlA-7285 + AGAAGGGGCCAGCCAGGCUGA 21 11134

SCNNlA-7286 + GAGAAGGGGCCAGCCAGGCUGA 22 11135

SCNNlA-7287 + GGAGAAGGGGCCAGCCAGGCUGA 23 11136

SCNNlA-7288 + AGGAGAAGGGGCCAGCCAGGCUGA 24 11137

SCNNlA-7289 + AGAAAGAGGGAGACAAUA 18 11138

1386

5535.1 SCNNlA-7290 + CAGAAAGAGGGAGACAAUA 19 11139

SCNNlA-7291 + GCAGAAAGAGGGAGACAAUA 20 11140

SCNNlA-7292 + GGCAGAAAGAGGGAGACAAUA 21 11141

SCNNlA-7293 + GGGCAGAAAGAGGGAGACAAUA 22 11142

SCNNlA-7294 + AGGGCAGAAAGAGGGAGACAAUA 23 11143

SCNNlA-7295 + GAGGGCAGAAAGAGGGAGACAAUA 24 11144

SCNNlA-7296 + UUUUUCUUCAUUGUCCUA 18 11145

SCNNlA-7297 + AUUUUUCUUCAUUGUCCUA 19 11146

SCNNlA-7298 + GAUUUUUCUUCAUUGUCCUA 20 11147

SCNNlA-7299 + GGAUUUUUCUUCAUUGUCCUA 21 11148

SCNNlA-7300 + UGGAUUUUUCUUCAUUGUCCUA 22 11149

SCNNlA-7301 + CUGGAUUUUUCUUCAUUGUCCUA 23 11150

SCNNlA-7302 + GCUGGAUUUUUCUUCAUUGUCCUA 24 11151

SCNNlA-7303 + CAUAAGAGCCAAGGGCUA 18 11152

SCNNlA-7304 + ACAUAAGAGCCAAGGGCUA 19 11153

SCNNlA-5198 + GACAUAAGAGCCAAGGGCUA 20 9047

SCNNlA-7305 + AGACAUAAGAGCCAAGGGCUA 21 11154

SCNNlA-7306 + AAGACAUAAGAGCCAAGGGCUA 22 11155

SCNNlA-7307 + UAAGACAUAAGAGCCAAGGGCUA 23 11156

SCNNlA-7308 + AUAAGACAUAAGAGCCAAGGGCUA 24 11157

SCNNlA-7309 + GCAGGUGAACUGGGAGUA 18 11158

SCNNlA-7310 + GGCAGGUGAACUGGGAGUA 19 11159

SCNNlA-7311 + GGGCAGGUGAACUGGGAGUA 20 11160

SCNNlA-7312 + AGGGCAGGUGAACUGGGAGUA 21 11161

SCNNlA-7313 + GAGGGCAGGUGAACUGGGAGUA 22 11162

SCNNlA-7314 + CGAGGGCAGGUGAACUGGGAGUA 23 11163

SCNNlA-7315 + CCGAGGGCAGGUGAACUGGGAGUA 24 11164

SCNNlA-7316 + UGCAGGAAUGUGGGCAAC 18 11165

SCNNlA-7317 + UUGCAGGAAUGUGGGCAAC 19 11166

SCNNlA-7318 + GUUGCAGGAAUGUGGGCAAC 20 11167

SCNNlA-7319 + AGUUGCAGGAAUGUGGGCAAC 21 11168

SCNNlA-7320 + GAGUUGCAGGAAUGUGGGCAAC 22 11169

SCNNlA-7321 + AGAGUUGCAGGAAUGUGGGCAAC 23 11170

SCNNlA-7322 + CAGAGUUGCAGGAAUGUGGGCAAC 24 11171

SCNNlA-7323 + AGGGCCUGGGUGGGGAAC 18 11172

SCNNlA-7324 + GAGGGCCUGGGUGGGGAAC 19 11173

SCNNlA-6101 + AGAGGGCCUGGGUGGGGAAC 20 9950

SCNNlA-7325 + GAGAGGGCCUGGGUGGGGAAC 21 11174

SCNNlA-7326 + UGAGAGGGCCUGGGUGGGGAAC 22 11175

SCNNlA-7327 + CUGAGAGGGCCUGGGUGGGGAAC 23 11176

SCNNlA-7328 + GCUGAGAGGGCCUGGGUGGGGAAC 24 11177

SCNNlA-7329 + UCCCGAGGGCAGGUGAAC 18 11178

1387

5535.1 SCNNlA-7330 + CUCCCGAGGGCAGGUGAAC 19 11179

SCNNlA-5203 + GCUCCCGAGGGCAGGUGAAC 20 9052

SCNNlA-7331 + GGCUCCCGAGGGCAGGUGAAC 21 11180

SCNNlA-7332 + GGGCUCCCGAGGGCAGGUGAAC 22 11181

SCNNlA-7333 + AGGGCUCCCGAGGGCAGGUGAAC 23 11182

SCNNlA-7334 + GAGGGCUCCCGAGGGCAGGUGAAC 24 11183

SCNNlA-7335 + CAGCUAGGAGGGCAACAC 18 11184

SCNNlA-7336 + ACAGCUAGGAGGGCAACAC 19 11185

SCNNlA-7337 + CACAGCUAGGAGGGCAACAC 20 11186

SCNNlA-7338 + CCACAGCUAGGAGGGCAACAC 21 11187

SCNNlA-7339 + CCCA CAGCUAGGAGGGCAACAC 22 11188

SCNNlA-7340 + GCCCA CAGCUAGGAGGGCAACAC 23 11189

SCNNlA-7341 + AGCCCACAGCUAGGAGGGCAACAC 24 11190

SCNNlA-7342 + CUGAGCAUUGAUACACAC 18 11191

SCNNlA-7343 + CCUGAGCAUUGAUACACAC 19 11192

SCNNlA-5204 + GCCUGAGCAUUGAUACACAC 20 9053

SCNNlA-7344 + AGCCUGAGCAUUGAUACACAC 21 11193

SCNNlA-7345 + CAGCCUGAGCAUUGAUACACAC 22 11194

SCNNlA-7346 + CCAGCCUGAGCAUUGAUACACAC 23 11195

SCNNlA-7347 + CCCAGCCUGAGCAUUGAUACACAC 24 11196

SCNNlA-7348 + CUUCCUCACGGGCCCCAC 18 11197

SCNNlA-7349 + GCUUCCUCACGGGCCCCAC 19 11198

SCNNlA-5561 + CGCUUCCUCACGGGCCCCAC 20 9410

SCNNlA-7350 + CCGCUUCCUCACGGGCCCCAC 21 11199

SCNNlA-7351 + GCCGCUUCCUCACGGGCCCCAC 22 11200

SCNNlA-7352 + UGCCGCUUCCUCACGGGCCCCAC 23 11201

SCNNlA-7353 + CUGCCGCUUCCUCACGGGCCCCAC 24 11202

SCNNlA-7354 + GACACUGUGGACACAGAC 18 11203

SCNNlA-7355 + GGACACUGUGGACACAGAC 19 11204

SCNNlA-7356 + AGGACACUGUGGACACAGAC 20 11205

SCNNlA-7357 + CAGGACACUGUGGACACAGAC 21 11206

SCNNlA-7358 + GCAGGACACUGUGGACACAGAC 22 11207

SCNNlA-7359 + CGCAGGACACUGUGGACACAGAC 23 11208

SCNNlA-7360 + ACGCAGGACACUGUGGACACAGAC 24 11209

SCNNlA-7361 + CUCCAACCUUGUCCAGAC 18 11210

SCNNlA-7362 + CCUCCAACCUUGUCCAGAC 19 11211

SCNNlA-7363 + CCCUCCAACCUUGUCCAGAC 20 11212

SCNNlA-7364 + CCCCUCCAACCUUGUCCAGAC 21 11213

SCNNlA-7365 + CCCCCUCCAACCUUGUCCAGAC 22 11214

SCNNlA-7366 + ACCCCCUCCAACCUUGUCCAGAC 23 11215

SCNNlA-7367 + CACCCCCUCCAACCUUGUCCAGAC 24 11216

SCNNlA-7368 + AAAAGGGCUGGAGGAGAC 18 11217

1388

5535.1 SCNNlA-7369 + AAAAAGGGCUGGAGGAGAC 19 11218

SCNNlA-7370 + CAAAAAGGGCUGGAGGAGAC 20 11219

SCNNlA-7371 + CCAAAAAGGGCUGGAGGAGAC 21 11220

SCNNlA-7372 + CCCAAAAAGGGCUGGAGGAGAC 22 11221

SCNNlA-7373 + ACCCAAAAAGGGCUGGAGGAGAC 23 11222

SCNNlA-7374 + GACCCAAAAAGGGCUGGAGGAGAC 24 11223

SCNNlA-7375 + GUGGGGAACCGGGAGGAC 18 11224

SCNNlA-7376 + GGUGGGGAACCGGGAGGAC 19 11225

SCNNlA-5209 + GGGUGGGGAACCGGGAGGAC 20 9058

SCNNlA-7377 + UGGGUGGGGAACCGGGAGGAC 21 11226

SCNNlA-7378 + CUGGGUGGGGAACCGGGAGGAC 22 11227

SCNNlA-7379 + CCUGGGUGGGGAACCGGGAGGAC 23 11228

SCNNlA-7380 + GCCUGGGUGGGGAACCGGGAGGAC 24 11229

SCNNlA-7381 + GAACUGGGAGUACUGGAC 18 11230

SCNNlA-7382 + UGAACUGGGAGUACUGGAC 19 11231

SCNNlA-7383 + GUGAACUGGGAGUACUGGAC 20 11232

SCNNlA-7384 + GGUGAACUGGGAGUACUGGAC 21 11233

SCNNlA-7385 + AGGUGAACUGGGAGUACUGGAC 22 11234

SCNNlA-7386 + CAGGUGAACUGGGAGUACUGGAC 23 11235

SCNNlA-7387 + GCAGGUGAACUGGGAGUACUGGAC 24 11236

SCNNlA-7388 + CCCAGGUUGCGGCUGGAC 18 11237

SCNNlA-7389 + UCCCAGGUUGCGGCUGGAC 19 11238

SCNNlA-5565 + CUCCCAGGUUGCGGCUGGAC 20 9414

SCNNlA-7390 + ACUCCCAGGUUGCGGCUGGAC 21 11239

SCNNlA-7391 + CACUCCCAGGUUGCGGCUGGAC 22 11240

SCNNlA-7392 + CCACUCCCAGGUUGCGGCUGGAC 23 11241

SCNNlA-7393 + CCCACUCCCAGGUUGCGGCUGGAC 24 11242

SCNNlA-7394 + GGGCCUGGGUGGGGAACC 18 11243

SCNNlA-7395 + AGGGCCUGGGUGGGGAACC 19 11244

SCNNlA-5214 + GAGGGCCUGGGUGGGGAACC 20 9063

SCNNlA-7396 + AGAGGGCCUGGGUGGGGAACC 21 11245

SCNNlA-7397 + GAGAGGGCCUGGGUGGGGAACC 22 11246

SCNNlA-7398 + UGAGAGGGCCUGGGUGGGGAACC 23 11247

SCNNlA-7399 + CUGAGAGGGCCUGGGUGGGGAACC 24 11248

SCNNlA-7400 + UGAGCAUUGAUACACACC 18 11249

SCNNlA-7401 + CUGAGCAUUGAUACACACC 19 11250

SCNNlA-5568 + CCUGAGCAUUGAUACACACC 20 9417

SCNNlA-7402 + GCCUGAGCAUUGAUACACACC 21 11251

SCNNlA-7403 + AGCCUGAGCAUUGAUACACACC 22 11252

SCNNlA-7404 + CAGCCUGAGCAUUGAUACACACC 23 11253

SCNNlA-7405 + CCAGCCUGAGCAUUGAUACACACC 24 11254

SCNNlA-7406 + ACACUGUGGACACAGACC 18 11255

1389

5535.1 SCNNlA-7407 + GACACUGUGGACACAGACC 19 11256

SCNNlA-5217 + GGACACUGUGGACACAGACC 20 9066

SCNNlA-7408 + AGGACACUGUGGACACAGACC 21 11257

SCNNlA-7409 + CAGGACACUGUGGACACAGACC 22 11258

SCNNlA-7410 + GCAGGACACUGUGGACACAGACC 23 11259

SCNNlA-7411 + CGCAGGACACUGUGGACACAGACC 24 11260

SCNNlA-7412 + UCCAACCUUGUCCAGACC 18 11261

SCNNlA-7413 + CUCCAACCUUGUCCAGACC 19 11262

SCNNlA-5569 + CCUCCAACCUUGUCCAGACC 20 9418

SCNNlA-7414 + CCCUCCAACCUUGUCCAGACC 21 11263

SCNNlA-7415 + CCCCUCCAACCUUGUCCAGACC 22 11264

SCNNlA-7416 + CCCCCUCCAACCUUGUCCAGACC 23 11265

SCNNlA-7417 + ACCCCCUCCAACCUUGUCCAGACC 24 11266

SCNNlA-7418 + CAGCCUCUGGCCCUGACC 18 11267

SCNNlA-7419 + CCAGCCUCUGGCCCUGACC 19 11268

SCNNlA-7420 + UCCAGCCUCUGGCCCUGACC 20 11269

SCNNlA-7421 + CUCCAGCCUCUGGCCCUGACC 21 11270

SCNNlA-7422 + GCUCCAGCCUCUGGCCCUGACC 22 11271

SCNNlA-7423 + AGCUCCAGCCUCUGGCCCUGACC 23 11272

SCNNlA-7424 + CAGCUCCAGCCUCUGGCCCUGACC 24 11273

SCNNlA-1484 + UGCCCUCUCCCAUCACCC 18 5333

SCNNlA-1485 + GUGCCCUCUCCCAUCACCC 19 5334

SCNNlA-1486 + AGUGCCCUCUCCCAUCACCC 20 5335

SCNNlA-1487 + GAGUGCCCUCUCCCAUCACCC 21 5336

SCNNlA-1488 + UGAGUGCCCUCUCCCAUCACCC 22 5337

SCNNlA-1489 + CUGAGUGCCCUCUCCCAUCACCC 23 5338

SCNNlA-1490 + CCUGAGUGCCCUCUCCCAUCACCC 24 5339

SCNNlA-7425 + CCAACCUUGUCCAGACCC 18 11274

SCNNlA-7426 + UCCAACCUUGUCCAGACCC 19 11275

SCNNlA-5572 + CUCCAACCUUGUCCAGACCC 20 9421

SCNNlA-7427 + CCUCCAACCUUGUCCAGACCC 21 11276

SCNNlA-7428 + CCCUCCAACCUUGUCCAGACCC 22 11277

SCNNlA-7429 + CCCCUCCAACCUUGUCCAGACCC 23 11278

SCNNlA-7430 + CCCCCUCCAACCUUGUCCAGACCC 24 11279

SCNNlA-1491 + GCCCUCUCCCAUCACCCC 18 5340

SCNNlA-1492 + UGCCCUCUCCCAUCACCCC 19 5341

SCNNlA-346 + GUGCCCUCUCCCAUCACCCC 20 4195

SCNNlA-1493 + AGUGCCCUCUCCCAUCACCCC 21 5342

SCNNlA-1494 + GAGUGCCCUCUCCCAUCACCCC 22 5343

SCNNlA-1495 + UGAGUGCCCUCUCCCAUCACCCC 23 5344

SCNNlA-1496 + CUGAGUGCCCUCUCCCAUCACCCC 24 5345

SCNNlA-7431 + ACAUAUCCCAGAGACCCC 18 11280

1390

5535.1 SCNNlA-7432 + CACAUAUCCCAGAGACCCC 19 11281

SCNNlA-7433 + CCACAUAUCCCAGAGACCCC 20 11282

SCNNlA-7434 + CCCACAUAUCCCAGAGACCCC 21 11283

SCNNlA-7435 + CCCCACAUAUCCCAGAGACCCC 22 11284

SCNNlA-7436 + GCCCCACAUAUCCCAGAGACCCC 23 11285

SCNNlA-7437 + UGCCCCACAUAUCCCAGAGACCCC 24 11286

SCNNlA-1497 + UGCUCAUGAUACCUCCCC 18 5346

SCNNlA-1498 + CUGCUCAUGAUACCUCCCC 19 5347

SCNNlA-1499 + ACUGCUCAUGAUACCUCCCC 20 5348

SCNNlA-1500 + UACUGCUCAUGAUACCUCCCC 21 5349

SCNNlA-1501 + AUACUGCUCAUGAUACCUCCCC 22 5350

SCNNlA-1502 + GAUACUGCUCAUGAUACCUCCCC 23 5351

SCNNlA-1503 + UGAUACUGCUCAUGAUACCUCCCC 24 5352

SCNNlA-7438 + GACACAGACCCGGAGCCC 18 11287

SCNNlA-7439 + GGACACAGACCCGGAGCCC 19 11288

SCNNlA-5575 + UGGACACAGACCCGGAGCCC 20 9424

SCNNlA-7440 + GUGGACACAGACCCGGAGCCC 21 11289

SCNNlA-7441 + UGUGGACACAGACCCGGAGCCC 22 11290

SCNNlA-7442 + CUGUGGACACAGACCCGGAGCCC 23 11291

SCNNlA-7443 + ACUGUGGACACAGACCCGGAGCCC 24 11292

SCNNlA-7444 + ACACGCCUAGACAGGCCC 18 11293

SCNNlA-7445 + CACACGCCUAGACAGGCCC 19 11294

SCNNlA-5219 + GCACACGCCUAGACAGGCCC 20 9068

SCNNlA-7446 + GGCACACGCCUAGACAGGCCC 21 11295

SCNNlA-7447 + UGGCACACGCCUAGACAGGCCC 22 11296

SCNNlA-7448 + AUGGCACACGCCUAGACAGGCCC 23 11297

SCNNlA-7449 + CAUGGCACACGCCUAGACAGGCCC 24 11298

SCNNlA-7450 + GGGGGCUAGGCGGGGCCC 18 11299

SCNNlA-7451 + UGGGGGCUAGGCGGGGCCC 19 11300

SCNNlA-7452 + CUGGGGGCUAGGCGGGGCCC 20 11301

SCNNlA-7453 + GCUGGGGGCUAGGCGGGGCCC 21 11302

SCNNlA-7454 + AGCUGGGGGCUAGGCGGGGCCC 22 11303

SCNNlA-7455 + AAGCUGGGGGCUAGGCGGGGCCC 23 11304

SCNNlA-7456 + GAAGCUGGGGGCUAGGCGGGGCCC 24 11305

SCNNlA-7457 + CUGAUUCUGUCUCUGCCC 18 11306

SCNNlA-7458 + CCUGAUUCUGUCUCUGCCC 19 11307

SCNNlA-7459 + UCCUGAUUCUGUCUCUGCCC 20 11308

SCNNlA-7460 + GUCCUGAUUCUGUCUCUGCCC 21 11309

SCNNlA-7461 + UGUCCUGAUUCUGUCUCUGCCC 22 11310

SCNNlA-7462 + GUGUCCUGAUUCUGUCUCUGCCC 23 11311

SCNNlA-7463 + UGUGUCCUGAUUCUGUCUCUGCCC 24 11312

SCNNlA-7464 + GAAGGAAGGAGGGCUCCC 18 11313

1391

5535.1 SCNNlA-7465 + CGAAGGAAGGAGGGCUCCC 19 11314

SCNNlA-7466 + CCGAAGGAAGGAGGGCUCCC 20 11315

SCNNlA-7467 + UCCGAAGGAAGGAGGGCUCCC 21 11316

SCNNlA-7468 + UUCCGAAGGAAGGAGGGCUCCC 22 11317

SCNNlA-7469 + UUUCCGAAGGAAGGAGGGCUCCC 23 11318

SCNNlA-7470 + UUUUCCGAAGGAAGGAGGGCUCCC 24 11319

SCNNlA-7471 + UAGAAACUCCAGUCUCCC 18 11320

SCNNlA-7472 + CUAGAAACUCCAGUCUCCC 19 11321

SCNNlA-7473 + CCUAGAAACUCCAGUCUCCC 20 11322

SCNNlA-7474 + CCCUAGAAACUCCAGUCUCCC 21 11323

SCNNlA-7475 + CCCCUAGAAACUCCAGUCUCCC 22 11324

SCNNlA-7476 + ACCCCUAGAAACUCCAGUCUCCC 23 11325

SCNNlA-7477 + GACCCCUAGAAACUCCAGUCUCCC 24 11326

SCNNlA-7478 + GCCGGAGCUGGGCUUCCC 18 11327

SCNNlA-7479 + UGCCGGAGCUGGGCUUCCC 19 11328

SCNNlA-7480 + GUGCCGGAGCUGGGCUUCCC 20 11329

SCNNlA-7481 + AGUGCCGGAGCUGGGCUUCCC 21 11330

SCNNlA-7482 + AAGUGCCGGAGCUGGGCUUCCC 22 11331

SCNNlA-7483 + AAAGUGCCGGAGCUGGGCUUCCC 23 11332

SCNNlA-7484 + AAAAGUGCCGGAGCUGGGCUUCCC 24 11333

SCNNlA-7485 + CACCUGGAUGUGAAAGCC 18 11334

SCNNlA-7486 + GCACCUGGAUGUGAAAGCC 19 11335

SCNNlA-6107 + UGCACCUGGAUGUGAAAGCC 20 9956

SCNNlA-7487 + GUGCACCUGGAUGUGAAAGCC 21 11336

SCNNlA-7488 + GGUGCACCUGGAUGUGAAAGCC 22 11337

SCNNlA-7489 + AGGUGCACCUGGAUGUGAAAGCC 23 11338

SCNNlA-7490 + CAGGUGCACCUGGAUGUGAAAGCC 24 11339

SCNNlA-7491 + AGAUAAGACAUAAGAGCC 18 11340

SCNNlA-7492 + GAGAUAAGACAUAAGAGCC 19 11341

SCNNlA-7493 + AGAGAUAAGACAUAAGAGCC 20 11342

SCNNlA-7494 + CAGAGAUAAGACAUAAGAGCC 21 11343

SCNNlA-7495 + UCAGAGAUAAGACAUAAGAGCC 22 11344

SCNNlA-7496 + CUCAGAGAUAAGACAUAAGAGCC 23 11345

SCNNlA-7497 + UCUCAGAGAUAAGACAUAAGAGCC 24 11346

SCNNlA-7498 + GGACACAGACCCGGAGCC 18 11347

SCNNlA-7499 + UGGACACAGACCCGGAGCC 19 11348

SCNNlA-7500 + GUGGACACAGACCCGGAGCC 20 11349

SCNNlA-7501 + UGUGGACACAGACCCGGAGCC 21 11350

SCNNlA-7502 + CUGUGGACACAGACCCGGAGCC 22 11351

SCNNlA-7503 + ACUGUGGACACAGACCCGGAGCC 23 11352

SCNNlA-7504 + CACUGUGGACACAGACCCGGAGCC 24 11353

SCNNlA-7505 + CCAAGGGCUAGGGGAGCC 18 11354

1392

5535.1 SCNNlA-7506 + GCCAAGGGCUAGGGGAGCC 19 11355

SCNNlA-7507 + AGCCAAGGGCUAGGGGAGCC 20 11356

SCNNlA-7508 + GAGCCAAGGGCUAGGGGAGCC 21 11357

SCNNlA-7509 + AGAGCCAAGGGCUAGGGGAGCC 22 11358

SCNNlA-7510 + AAGAGCCAAGGGCUAGGGGAGCC 23 11359

SCNNlA-7511 + UAAGAGCCAAGGGCUAGGGGAGCC 24 11360

SCNNlA-1504 + UGUUCCCCUUCAUGAGCC 18 5353

SCNNlA-1505 + UUGUUCCCCUUCAUGAGCC 19 5354

SCNNlA-207 + CUUGUUCCCCUUCAUGAGCC 20 834

SCNNlA-1506 + GCUUGUUCCCCUUCAUGAGCC 21 5355

SCNNlA-1507 + AGCUUGUUCCCCUUCAUGAGCC 22 5356

SCNNlA-1508 + CAGCUUGUUCCCCUUCAUGAGCC 23 5357

SCNNlA-1509 + CCAGCUUGUUCCCCUUCAUGAGCC 24 5358

SCNNlA-7512 + CACACGCCUAGACAGGCC 18 11361

SCNNlA-7513 + GCACACGCCUAGACAGGCC 19 11362

SCNNlA-7514 + GGCACACGCCUAGACAGGCC 20 11363

SCNNlA-7515 + UGGCACACGCCUAGACAGGCC 21 11364

SCNNlA-7516 + AUGGCACACGCCUAGACAGGCC 22 11365

SCNNlA-7517 + CAUGGCACACGCCUAGACAGGCC 23 11366

SCNNlA-7518 + GCAUGGCACACGCCUAGACAGGCC 24 11367

SCNNlA-7519 + CCACUGCCCCACAUAUCC 18 11368

SCNNlA-7520 + CCCACUGCCCCACAUAUCC 19 11369

SCNNlA-7521 + CCCCACUGCCCCACAUAUCC 20 11370

SCNNlA-7522 + UCCCCACUGCCCCACAUAUCC 21 11371

SCNNlA-7523 + GUCCCCACUGCCCCACAUAUCC 22 11372

SCNNlA-7524 + UGUCCCCACUGCCCCACAUAUCC 23 11373

SCNNlA-7525 + CUGUCCCCACUGCCCCACAUAUCC 24 11374

SCNNlA-1525 + UCCAGCUUGUUCCCCUCC 18 5374

SCNNlA-1526 + CUCCAGCUUGUUCCCCUCC 19 5375

SCNNlA-200 + CCUCCAGCUUGUUCCCCUCC 20 829

SCNNlA-1527 + UCCUCCAGCUUGUUCCCCUCC 21 5376

SCNNlA-1528 + CUCCUCCAGCUUGUUCCCCUCC 22 5377

SCNNlA-1529 + GCUCCUCCAGCUUGUUCCCCUCC 23 5378

SCNNlA-1530 + UGCUCCUCCAGCUUGUUCCCCUCC 24 5379

SCNNlA-7526 + GCAAGUGGGCAGCCCUCC 18 11375

SCNNlA-7527 + AGCAAGUGGGCAGCCCUCC 19 11376

SCNNlA-7528 + CAGCAAGUGGGCAGCCCUCC 20 11377

SCNNlA-7529 + UCAGCAAGUGGGCAGCCCUCC 21 11378

SCNNlA-7530 + CUCAGCAAGUGGGCAGCCCUCC 22 11379

SCNNlA-7531 + GCUCAGCAAGUGGGCAGCCCUCC 23 11380

SCNNlA-7532 + GGCUCAGCAAGUGGGCAGCCCUCC 24 11381

SCNNlA-7533 + CCAGGACUGCAGGGCUCC 18 11382

1393

5535.1 SCNNlA-7534 + CCCAGGACUGCAGGGCUCC 19 11383

SCNNlA-6112 + CCCCAGGACUGCAGGGCUCC 20 9961

SCNNlA-7535 + GCCCCAGGACUGCAGGGCUCC 21 11384

SCNNlA-7536 + UGCCCCAGGACUGCAGGGCUCC 22 11385

SCNNlA-7537 + CUGCCCCAGGACUGCAGGGCUCC 23 11386

SCNNlA-7538 + UCUGCCCCAGGACUGCAGGGCUCC 24 11387

SCNNlA-7539 + CAAAGGGAGUCUGUCUCC 18 11388

SCNNlA-7540 + CCAAAGGGAGUCUGUCUCC 19 11389

SCNNlA-5596 + ACCAAAGGGAGUCUGUCUCC 20 9445

SCNNlA-7541 + CACCAAAGGGAGUCUGUCUCC 21 11390

SCNNlA-7542 + GCACCAAAGGGAGUCUGUCUCC 22 11391

SCNNlA-7543 + AGCACCAAAGGGAGUCUGUCUCC 23 11392

SCNNlA-7544 + CAGCACCAAAGGGAGUCUGUCUCC 24 11393

SCNNlA-7545 + AGACUCAGGAAGCCUUCC 18 11394

SCNNlA-7546 + GAGACUCAGGAAGCCUUCC 19 11395

SCNNlA-7547 + GGAGACUCAGGAAGCCUUCC 20 11396

SCNNlA-7548 + AGGAGACUCAGGAAGCCUUCC 21 11397

SCNNlA-7549 + CAGGAGACUCAGGAAGCCUUCC 22 11398

SCNNlA-7550 + GCAGGAGACUCAGGAAGCCUUCC 23 11399

SCNNlA-7551 + UGCAGGAGACUCAGGAAGCCUUCC 24 11400

SCNNlA-7552 + AGUCCCAAGUGUGCUUCC 18 11401

SCNNlA-7553 + GAGUCCCAAGUGUGCUUCC 19 11402

SCNNlA-5226 + GGAGUCCCAAGUGUGCUUCC 20 9075

SCNNlA-7554 + GGGAGUCCCAAGUGUGCUUCC 21 11403

SCNNlA-7555 + GGGGAGUCCCAAGUGUGCUUCC 22 11404

SCNNlA-7556 + GGGGGAGUCCCAAGUGUGCUUCC 23 11405

SCNNlA-7557 + GGGGGGAGUCCCAAGUGUGCUUCC 24 11406

SCNNlA-7558 + UCCCUCCUCCACCUUUCC 18 11407

SCNNlA-7559 + CUCCCUCCUCCACCUUUCC 19 11408

SCNNlA-6116 + CCUCCCUCCUCCACCUUUCC 20 9965

SCNNlA-7560 + CCCUCCCUCCUCCACCUUUCC 21 11409

SCNNlA-7561 + UCCCUCCCUCCUCCACCUUUCC 22 11410

SCNNlA-7562 + CUCCCUCCCUCCUCCACCUUUCC 23 11411

SCNNlA-7563 + CCUCCCUCCCUCCUCCACCUUUCC 24 11412

SCNNlA-7564 + GCACCUGGAUGUGAAAGC 18 11413

SCNNlA-7565 + UGCACCUGGAUGUGAAAGC 19 11414

SCNNlA-5227 + GUGCACCUGGAUGUGAAAGC 20 9076

SCNNlA-7566 + GGUGCACCUGGAUGUGAAAGC 21 11415

SCNNlA-7567 + AGGUGCACCUGGAUGUGAAAGC 22 11416

SCNNlA-7568 + CAGGUGCACCUGGAUGUGAAAGC 23 11417

SCNNlA-7569 + UCAGGUGCACCUGGAUGUGAAAGC 24 11418

SCNNlA-7570 + UGCUGAAUCUUGACAAGC 18 11419

1394

5535.1 SCNNlA-7571 + CUGCUGAAUCUUGACAAGC 19 11420

SCNNlA-7572 + UCUGCUGAAUCUUGACAAGC 20 11421

SCNNlA-7573 + CUCUGCUGAAUCUUGACAAGC 21 11422

SCNNlA-7574 + UCUCUGCUGAAUCUUGACAAGC 22 11423

SCNNlA-7575 + AUCUCUGCUGAAUCUUGACAAGC 23 11424

SCNNlA-7576 + CAUCUCUGCUGAAUCUUGACAAGC 24 11425

SCNNlA-7577 + GAGGGGCCCAGGUGAAGC 18 11426

SCNNlA-7578 + GGAGGGGCCCAGGUGAAGC 19 11427

SCNNlA-5885 + GGGAGGGGCCCAGGUGAAGC 20 9734

SCNNlA-7579 + CGGGAGGGGCCCAGGUGAAGC 21 11428

SCNNlA-7580 + CCGGGAGGGGCCCAGGUGAAGC 22 11429

SCNNlA-7581 + CCCGGGAGGGGCCCAGGUGAAGC 23 11430

SCNNlA-7582 + ACCCGGGAGGGGCCCAGGUGAAGC 24 11431

SCNNlA-7583 + GGAUCCUGAGCCCACAGC 18 11432

SCNNlA-7584 + AGGAUCCUGAGCCCACAGC 19 11433

SCNNlA-7585 + AAGGAUCCUGAGCCCACAGC 20 11434

SCNNlA-7586 + GAAGGAUCCUGAGCCCACAGC 21 11435

SCNNlA-7587 + AGAAGGAUCCUGAGCCCACAGC 22 11436

SCNNlA-7588 + UAGAAGGAUCCUGAGCCCACAGC 23 11437

SCNNlA-7589 + GUAGAAGGAUCCUGAGCCCACAGC 24 11438

SCNNlA-7590 + AGCAGACAAAGGCCCAGC 18 11439

SCNNlA-7591 + C AG C AG AC A A AG G C C C AG C 19 11440

SCNNlA-7592 + C C AG C AG AC A A AG G C C C AG C 20 11441

SCNNlA-7593 + G CCAGCAG ACAAAGG CCCAG C 21 11442

SCNNlA-7594 + AGCCAGCAGACAAAGGCCCAGC 22 11443

SCNNlA-7595 + AAGCCAG CAG ACAAAGG CCCAG C 23 11444

SCNNlA-7596 + CAAGCCAG CAG ACAAAGG CCCAG C 24 11445

SCNNlA-7597 + UGGGCAACCAGAGGCAGC 18 11446

SCNNlA-7598 + GUGGGCAACCAGAGGCAGC 19 11447

SCNNlA-7599 + UGUGGGCAACCAGAGGCAGC 20 11448

SCNNlA-7600 + AUGUGGGCAACCAGAGGCAGC 21 11449

SCNNlA-7601 + AAUGUGGGCAACCAGAGGCAGC 22 11450

SCNNlA-7602 + GAAUGUGGGCAACCAGAGGCAGC 23 11451

SCNNlA-7603 + GGAAUGUGGGCAACCAGAGGCAGC 24 11452

SCNNlA-7604 + CUGAGGAGGAGUCAGAGC 18 11453

SCNNlA-7605 + GCUGAGGAGGAGUCAGAGC 19 11454

SCNNlA-5886 + GGCUGAGGAGGAGUCAGAGC 20 9735

SCNNlA-7606 + GGGCUGAGGAGGAGUCAGAGC 21 11455

SCNNlA-7607 + GGGGCUGAGGAGGAGUCAGAGC 22 11456

SCNNlA-7608 + AGGGGCUGAGGAGGAGUCAGAGC 23 11457

SCNNlA-7609 + GAGGGGCUGAGGAGGAGUCAGAGC 24 11458

SCNNlA-7610 + GUCUCCAGGAAGGAGAGC 18 11459

1395

5535.1 SCNNlA-7611 + UGUCUCCAGGAAGGAGAGC 19 11460

SCNNlA-7612 + CUGUCUCCAGGAAGGAGAGC 20 11461

SCNNlA-7613 + UCUGUCUCCAGGAAGGAGAGC 21 11462

SCNNlA-7614 + GUCUGUCUCCAGGAAGGAGAGC 22 11463

SCNNlA-7615 + AGUCUGUCUCCAGGAAGGAGAGC 23 11464

SCNNlA-7616 + GAGUCUGUCUCCAGGAAGGAGAGC 24 11465

SCNNlA-7617 + AAGUGUGCUUCCAGGAGC 18 11466

SCNNlA-7618 + CAAGUGUGCUUCCAGGAGC 19 11467

SCNNlA-7619 + CCAAGUGUGCUUCCAGGAGC 20 11468

SCNNlA-7620 + CCCAAGUGUGCUUCCAGGAGC 21 11469

SCNNlA-7621 + UCCCAAGUGUGCUUCCAGGAGC 22 11470

SCNNlA-7622 + GUCCCAAGUGUGCUUCCAGGAGC 23 11471

SCNNlA-7623 + AGUCCCAAGUGUGCUUCCAGGAGC 24 11472

SCNNlA-7624 + GAGUGCCAAGUGGUGAGC 18 11473

SCNNlA-7625 + GGAGUGCCAAGUGGUGAGC 19 11474

SCNNlA-7626 + UGGAGUGCCAAGUGGUGAGC 20 11475

SCNNlA-7627 + GUGGAGUGCCAAGUGGUGAGC 21 11476

SCNNlA-7628 + AGUGGAGUGCCAAGUGGUGAGC 22 11477

SCNNlA-7629 + GAGUGGAGUGCCAAGUGGUGAGC 23 11478

SCNNlA-7630 + GGAGUGGAGUGCCAAGUGGUGAGC 24

11479

SCNNlA-7631 + GGAGGAUGUGGCCAGCGC 18 11480

SCNNlA-7632 + GGGAGGAUGUGGCCAGCGC 19 11481

SCNNlA-6120 + AGGGAGGAUGUGGCCAGCGC 20 9969

SCNNlA-7633 + CAGGGAGGAUGUGGCCAGCGC 21 11482

SCNNlA-7634 + GCAGGGAGGAUGUGGCCAGCGC 22 11483

SCNNlA-7635 + UGCAGGGAGGAUGUGGCCAGCGC 23 11484

SCNNlA-7636 + GUGCAGGGAGGAUGUGGCCAGCGC 24 11485

SCNNlA-7637 + GGCAACCAGAGGCAGCGC 18 11486

SCNNlA-7638 + GGGCAACCAGAGGCAGCGC 19 11487

SCNNlA-7639 + UGGGCAACCAGAGGCAGCGC 20 11488

SCNNlA-7640 + GUGGGCAACCAGAGGCAGCGC 21 11489

SCNNlA-7641 + UGUGGGCAACCAGAGGCAGCGC 22 11490

SCNNlA-7642 + AUGUGGGCAACCAGAGGCAGCGC 23 11491

SCNNlA-7643 + AAUGUGGGCAACCAGAGGCAGCGC 24 11492

SCNNlA-7644 + CUUUAGACGCAGACAGGC 18 11493

SCNNlA-7645 + GCUUUAGACGCAGACAGGC 19 11494

SCNNlA-7646 + GGCUUUAGACGCAGACAGGC 20 11495

SCNNlA-7647 + GGGCUUUAGACGCAGACAGGC 21 11496

SCNNlA-7648 + GGGGCUUUAGACGCAGACAGGC 22 11497

SCNNlA-7649 + AGGGGCUUUAGACGCAGACAGGC 23 11498

SCNNlA-7650 + CAGGGGCUUUAGACGCAGACAGGC 24 11499

1396

5535.1 SCNNlA-7651 + CACUGUUGGCUGCCAGGC 18 11500

SCNNlA-7652 + ACACUGUUGGCUGCCAGGC 19 11501

SCNNlA-7653 + UACACUGUUGGCUGCCAGGC 20 11502

SCNNlA-7654 + UUACACUGUUGGCUGCCAGGC 21 11503

SCNNlA-7655 + UUUACACUGUUGGCUGCCAGGC 22 11504

SCNNlA-7656 + UUUUACACUGUUGGCUGCCAGGC 23 11505

SCNNlA-7657 + UUUUUACACUGUUGGCUGCCAGGC 24 11506

SCNNlA-7658 + CGGAGCCCAGGAAGAGGC 18 11507

SCNNlA-7659 + CCGGAGCCCAGGAAGAGGC 19 11508

SCNNlA-6122 + CCCGGAGCCCAGGAAGAGGC 20 9971

SCNNlA-7660 + ACCCGGAGCCCAGGAAGAGGC 21 11509

SCNNlA-7661 + GACCCGGAGCCCAGGAAGAGGC 22 11510

SCNNlA-7662 + AGACCCGGAGCCCAGGAAGAGGC 23 11511

SCNNlA-7663 + CAGACCCGGAGCCCAGGAAGAGGC 24 11512

SCNNlA-7664 + GCAGACAGGCAAGGAGGC 18 11513

SCNNlA-7665 + CGCAGACAGGCAAGGAGGC 19 11514

SCNNlA-5608 + ACGCAGACAGGCAAGGAGGC 20 9457

SCNNlA-7666 + GACGCAGACAGGCAAGGAGGC 21 11515

SCNNlA-7667 + AGACGCAGACAGGCAAGGAGGC 22 11516

SCNNlA-7668 + UAGACGCAGACAGGCAAGGAGGC 23 11517

SCNNlA-7669 + UUAGACGCAGACAGGCAAGGAGGC 24 11518

SCNNlA-7670 + GCCCGCCCGCUGGCCGGC 18 11519

SCNNlA-7671 + AGCCCGCCCGCUGGCCGGC 19 11520

SCNNlA-7672 + GAGCCCGCCCGCUGGCCGGC 20 11521

SCNNlA-7673 + GGAGCCCGCCCGCUGGCCGGC 21 11522

SCNNlA-7674 + GGGAGCCCGCCCGCUGGCCGGC 22 11523

SCNNlA-7675 + GGGGAGCCCGCCCGCUGGCCGGC 23 11524

SCNNlA-7676 + UGGGGAGCCCGCCCGCUGGCCGGC 24 11525

SCNNlA-7677 + CCAGGCCCUGCACGCGGC 18 11526

SCNNlA-7678 + CCCAGGCCCUGCACGCGGC 19 11527

SCNNlA-5609 + ACCCAGGCCCUGCACGCGGC 20 9458

SCNNlA-7679 + AACCCAGGCCCUGCACGCGGC 21 11528

SCNNlA-7680 + CAACCCAGGCCCUGCACGCGGC 22 11529

SCNNlA-7681 + ACAACCCAGGCCCUGCACGCGGC 23 11530

SCNNlA-7682 + CACAACCCAGGCCCUGCACGCGGC 24 11531

SCNNlA-7683 + AUCAGACCCAAAAAGGGC 18 11532

SCNNlA-7684 + AAUCAGACCCAAAAAGGGC 19 11533

SCNNlA-5232 + GAAUCAGACCCAAAAAGGGC 20 9081

SCNNlA-7685 + AGAAUCAGACCCAAAAAGGGC 21 11534

SCNNlA-7686 + GAGAAUCAGACCCAAAAAGGGC 22 11535

SCNNlA-7687 + AGAGAAUCAGACCCAAAAAGGGC 23 11536

SCNNlA-7688 + CAGAGAAUCAGACCCAAAAAGGGC 24 11537

1397

5535.1 SCNNlA-7689 + GACAUAAGAGCCAAGGGC 18 11538

SCNNlA-7690 + AGACAUAAGAGCCAAGGGC 19 11539

SCNNlA-7691 + AAGACAUAAGAGCCAAGGGC 20 11540

SCNNlA-7692 + UAAGACAUAAGAGCCAAGGGC 21 11541

SCNNlA-7693 + AUAAGACAUAAGAGCCAAGGGC 22 11542

SCNNlA-7694 + GAUAAGACAUAAGAGCCAAGGGC 23 11543

SCNNlA-7695 + AGAUAAGACAUAAGAGCCAAGGGC 24 11544

SCNNlA-7696 + AUUAAAGGUGAGCAGGGC 18 11545

SCNNlA-7697 + AAUUAAAGGUGAGCAGGGC 19 11546

SCNNlA-5611 + C A A U U A A AG GUGAGCAGGGC 20 9460

SCNNlA-7698 + UCAAUUAAAGGUGAGCAGGGC 21 11547

SCNNlA-7699 + CUCAAUUAAAGGUGAGCAGGGC 22 11548

SCNNlA-7700 + UCUCAAUUAAAGGUGAGCAGGGC 23 11549

SCNNlA-7701 + AUCUCAAUUAAAGGUGAGCAGGGC 24 11550

SCNNlA-7702 + AGAAGGCGGACUCUGGGC 18 11551

SCNNlA-7703 + GAGAAGGCGGACUCUGGGC 19 11552

SCNNlA-5613 + UGAGAAGGCGGACUCUGGGC 20 9462

SCNNlA-7704 + CUGAGAAGGCGGACUCUGGGC 21 11553

SCNNlA-7705 + CCUGAGAAGGCGGACUCUGGGC 22 11554

SCNNlA-7706 + ACCUGAGAAGGCGGACUCUGGGC 23 11555

SCNNlA-7707 + GACCUGAGAAGGCGGACUCUGGGC 24 11556

SCNNlA-7708 + CAGGUGCAGCGGCCUGGC 18 11557

SCNNlA-7709 + ACAGGUGCAGCGGCCUGGC 19 11558

SCNNlA-5234 + GACAGGUGCAGCGGCCUGGC 20 9083

SCNNlA-7710 + UGACAGGUGCAGCGGCCUGGC 21 11559

SCNNlA-7711 + CUGACAGGUGCAGCGGCCUGGC 22 11560

SCNNlA-7712 + CCUGACAGGUGCAGCGGCCUGGC 23 11561

SCNNlA-7713 + ACCUGACAGGUGCAGCGGCCUGGC 24 11562

SCNNlA-7714 + CUAUUUGCCAGCUCAUGC 18 11563

SCNNlA-7715 + UCUAUUUGCCAGCUCAUGC 19 11564

SCNNlA-7716 + UUCUAUUUGCCAGCUCAUGC 20 11565

SCNNlA-7717 + UUUCUAUUUGCCAGCUCAUGC 21 11566

SCNNlA-7718 + UUUUCUAUUUGCCAGCUCAUGC 22 11567

SCNNlA-7719 + CUUUUCUAUUUGCCAGCUCAUGC 23 11568

SCNNlA-7720 + CCUUUUCUAUUUGCCAGCUCAUGC 24 11569

SCNNlA-7721 + AGCCUAGGGGCUCACUGC 18 11570

SCNNlA-7722 + GAGCCUAGGGGCUCACUGC 19 11571

SCNNlA-5235 + GGAGCCUAGGGGCUCACUGC 20 9084

SCNNlA-7723 + GGGAGCCUAGGGGCUCACUGC 21 11572

SCNNlA-7724 + GGGGAGCCUAGGGGCUCACUGC 22 11573

SCNNlA-7725 + AGGGGAGCCUAGGGGCUCACUGC 23 11574

SCNNlA-7726 + UAGGGGAGCCUAGGGGCUCACUGC 24 11575

1398

5535.1 SCNNlA-7727 + AGUUGGGGCCAAAAGUGC 18 11576

SCNNlA-7728 + GAGUUGGGGCCAAAAGUGC 19 11577

SCNNlA-5236 + GGAGUUGGGGCCAAAAGUGC 20 9085

SCNNlA-7729 + GGGAGUUGGGGCCAAAAGUGC 21 11578

SCNNlA-7730 + CGGGAGUUGGGGCCAAAAGUGC 22 11579

SCNNlA-7731 + GCGGGAGUUGGGGCCAAAAGUGC 23 11580

SCNNlA-7732 + UGCGGGAGUUGGGGCCAAAAGUGC 24 11581

SCNNlA-7733 + AGCAGGCACUGAAGGUGC 18 11582

SCNNlA-7734 + AAG C AGG CAC U G AAG G U G C 19 11583

SCNNlA-5620 + AAAG C AGG CAC U G AAG G U G C 20 9469

SCNNlA-7735 + GAAAGCAGGCACUGAAGGUGC 21 11584

SCNNlA-7736 + GGAAAGCAGGCACUGAAGGUGC 22 11585

SCNNlA-7737 + GGGAAAGCAGGCACUGAAGGUGC 23 11586

SCNNlA-7738 + AGGGAAAGCAGGCACUGAAGGUGC 24 11587

SCNNlA-7739 + UGAACAAGUAGAAGGAUC 18 11588

SCNNlA-7740 + CUGAACAAGUAGAAGGAUC 19 11589

SCNNlA-7741 + UCUGAACAAGUAGAAGGAUC 20 11590

SCNNlA-7742 + AUCUGAACAAGUAGAAGGAUC 21 11591

SCNNlA-7743 + GAUCUGAACAAGUAGAAGGAUC 22 11592

SCNNlA-7744 + AGAUCUGAACAAGUAGAAGGAUC 23 11593

SCNNlA-7745 + AAGAUCUGAACAAGUAGAAGGAUC 24 11594

SCNNlA-7746 + GCAAAUAGUUUUCAUAUC 18 11595

SCNNlA-7747 + GGCAAAUAGUUUUCAUAUC 19 11596

SCNNlA-7748 + UGGCAAAUAGUUUUCAUAUC 20 11597

SCNNlA-7749 + AUGGCAAAUAGUUUUCAUAUC 21 11598

SCNNlA-7750 + CAUGGCAAAUAGUUUUCAUAUC 22 11599

SCNNlA-7751 + GCAUGGCAAAUAGUUUUCAUAUC 23 11600

SCNNlA-7752 + AGCAUGGCAAAUAGUUUUCAUAUC 24 11601

SCNNlA-7753 + ACUUCCUGAGACAGACUC 18 11602

SCNNlA-7754 + UACUUCCUGAGACAGACUC 19 11603

SCNNlA-7755 + UUACUUCCUGAGACAGACUC 20 11604

SCNNlA-7756 + UUUACUUCCUGAGACAGACUC 21 11605

SCNNlA-7757 + AUUUACUUCCUGAGACAGACUC 22 11606

SCNNlA-7758 + CAUUUACUUCCUGAGACAGACUC 23 11607

SCNNlA-7759 + CCAUUUACUUCCUGAGACAGACUC 24 11608

SCNNlA-7760 + GCUCACUGCAGGAGACUC 18 11609

SCNNlA-7761 + GGCUCACUGCAGGAGACUC 19 11610

SCNNlA-5239 + GGGCUCACUGCAGGAGACUC 20 9088

SCNNlA-7762 + GGGGCUCACUGCAGGAGACUC 21 11611

SCNNlA-7763 + AGGGGCUCACUGCAGGAGACUC 22 11612

SCNNlA-7764 + UAGGGGCUCACUGCAGGAGACUC 23 11613

SCNNlA-7765 + CUAGGGGCUCACUGCAGGAGACUC 24 11614

1399

5535.1 SCNNlA-7766 + AAGGGCUGGAGGAGACUC 18 11615

SCNNlA-7767 + AAAGGGCUGGAGGAGACUC 19 11616

SCNNlA-5628 + AAAAGGGCUGGAGGAGACUC 20 9477

SCNNlA-7768 + AAAAAGGGCUGGAGGAGACUC 21 11617

SCNNlA-7769 + CAAAAAGGGCUGGAGGAGACUC 22 11618

SCNNlA-7770 + CCAAAAAGGGCUGGAGGAGACUC 23 11619

SCNNlA-7771 + CCCAAAAAGGGCUGGAGGAGACUC 24 11620

SCNNlA-7772 + AGAAUUCUCCUCCUCCUC 18 11621

SCNNlA-7773 + CAGAAUUCUCCUCCUCCUC 19 11622

SCNNlA-6134 + UCAGAAUUCUCCUCCUCCUC 20 9983

SCNNlA-7774 + UUCAGAAUUCUCCUCCUCCUC 21 11623

SCNNlA-7775 + AUUCAGAAUUCUCCUCCUCCUC 22 11624

SCNNlA-7776 + AAUUCAGAAUUCUCCUCCUCCUC 23 11625

SCNNlA-7777 + GAAUUCAGAAUUCUCCUCCUCCUC 24 11626

SCNNlA-7778 + GAAGGCUGCCGCUUCCUC 18 11627

SCNNlA-7779 + GGAAGGCUGCCGCUUCCUC 19 11628

SCNNlA-7780 + GGGAAGGCUGCCGCUUCCUC 20 11629

SCNNlA-7781 + AGGGAAGGCUGCCGCUUCCUC 21 11630

SCNNlA-7782 + CAGGGAAGGCUGCCGCUUCCUC 22 11631

SCNNlA-7783 + GCAGGGAAGGCUGCCGCUUCCUC 23 11632

SCNNlA-7784 + GGCAGGGAAGGCUGCCGCUUCCUC 24 11633

SCNNlA-7785 + CCCAGGACUGCAGGGCUC 18 11634

SCNNlA-7786 + CCCCAGGACUGCAGGGCUC 19 11635

SCNNlA-7787 + GCCCCAGGACUGCAGGGCUC 20 11636

SCNNlA-7788 + UGCCCCAGGACUGCAGGGCUC 21 11637

SCNNlA-7789 + CUGCCCCAGGACUGCAGGGCUC 22 11638

SCNNlA-7790 + UCUGCCCCAGGACUGCAGGGCUC 23 11639

SCNNlA-7791 + CUCUGCCCCAGGACUGCAGGGCUC 24 11640

SCNNlA-7792 + CCGAAGGAAGGAGGGCUC 18 11641

SCNNlA-7793 + UCCGAAGGAAGGAGGGCUC 19 11642

SCNNlA-7794 + UUCCGAAGGAAGGAGGGCUC 20 11643

SCNNlA-7795 + UUUCCGAAGGAAGGAGGGCUC 21 11644

SCNNlA-7796 + UUUUCCGAAGGAAGGAGGGCUC 22 11645

SCNNlA-7797 + GUUUUCCGAAGGAAGGAGGGCUC 23 11646

SCNNlA-7798 + AGUUUUCCGAAGGAAGGAGGGCUC 24 11647

SCNNlA-7799 + CCAAAGGGAGUCUGUCUC 18 11648

SCNNlA-7800 + ACCAAAGGGAGUCUGUCUC 19 11649

SCNNlA-7801 + CACCAAAGGGAGUCUGUCUC 20 11650

SCNNlA-7802 + GCACCAAAGGGAGUCUGUCUC 21 11651

SCNNlA-7803 + AGCACCAAAGGGAGUCUGUCUC 22 11652

SCNNlA-7804 + CAGCACCAAAGGGAGUCUGUCUC 23 11653

SCNNlA-7805 + CCAGCACCAAAGGGAGUCUGUCUC 24 11654

1400

5535.1 SCNNlA-7806 + GCUUUUGCCAUUUACUUC 18 11655

SCNNlA-7807 + CGCUUUUGCCAUUUACUUC 19 11656

SCNNlA-7808 + GCGCUUUUGCCAUUUACUUC 20 11657

SCNNlA-7809 + AGCGCUUUUGCCAUUUACUUC 21 11658

SCNNlA-7810 + UAGCGCUUUUGCCAUUUACUUC 22 11659

SCNNlA-7811 + UUAGCGCUUUUGCCAUUUACUUC 23 11660

SCNNlA-7812 + CUUAGCGCUUUUGCCAUUUACUUC 24 11661

SCNNlA-1549 + UCCAGCUUGUUCCCCUUC 18 5398

SCNNlA-1550 + CUCCAGCUUGUUCCCCUUC 19 5399

SCNNlA-1551 + CCUCCAGCUUGUUCCCCUUC 20 5400

SCNNlA-1552 + UCCUCCAGCUUGUUCCCCUUC 21 5401

SCNNlA-1553 + CUCCUCCAGCUUGUUCCCCUUC 22 5402

SCNNlA-1554 + GCUCCUCCAGCUUGUUCCCCUUC 23 5403

SCNNlA-1555 + UGCUCCUCCAGCUUGUUCCCCUUC 24 5404

SCNNlA-7813 + GAGUCCCAAGUGUGCUUC 18 11662

SCNNlA-7814 + GGAGUCCCAAGUGUGCUUC 19 11663

SCNNlA-7815 + GGGAGUCCCAAGUGUGCUUC 20 11664

SCNNlA-7816 + GGGGAGUCCCAAGUGUGCUUC 21 11665

SCNNlA-7817 + GGGGGAGUCCCAAGUGUGCUUC 22 11666

SCNNlA-7818 + GGGGGGAGUCCCAAGUGUGCUUC 23 11667

SCNNlA-7819 + AGGGGGGAGUCCCAAGUGUGCUUC 24 11668

SCNNlA-7820 + CUCCCUCCUCCACCUUUC 18 11669

SCNNlA-7821 + CCUCCCUCCUCCACCUUUC 19 11670

SCNNlA-7822 + CCCUCCCUCCUCCACCUUUC 20 11671

SCNNlA-7823 + UCCCUCCCUCCUCCACCUUUC 21 11672

SCNNlA-7824 + CUCCCUCCCUCCUCCACCUUUC 22 11673

SCNNlA-7825 + CCUCCCUCCCUCCUCCACCUUUC 23 11674

SCNNlA-7826 + UCCUCCCUCCCUCCUCCACCUUUC 24 11675

SCNNlA-7827 + GGAGUUUAGCAGGCAAAG 18 11676

SCNNlA-7828 + AGGAGUUUAGCAGGCAAAG 19 11677

SCNNlA-7829 + AAGGAGUUUAGCAGGCAAAG 20 11678

SCNNlA-7830 + CAAGGAGUUUAGCAGGCAAAG 21 11679

SCNNlA-7831 + G C A AG GAG UUUAGCAGG C A A AG 22 11680

SCNNlA-7832 + AGCAAGGAGUUUAGCAGGCAAAG 23 11681

SCNNlA-7833 + AAGCAAGGAGUUUAGCAGG C A A AG 24 11682

SCNNlA-7834 + GGACAGGAGGGCAGAAAG 18 11683

SCNNlA-7835 + AGGACAGGAGGGCAGAAAG 19 11684

SCNNlA-5894 + GAGGACAGGAGGGCAGAAAG 20 9743

SCNNlA-7836 + GGAGGACAGGAGGGCAGAAAG 21 11685

SCNNlA-7837 + GGGAGGACAGGAGGGCAGAAAG 22 11686

SCNNlA-7838 + CGGGAGGACAGGAGGGCAGAAAG 23 11687

SCNNlA-7839 + CCGGGAGGACAGGAGGGCAGAAAG 24 11688

1401

5535.1 SCNNlA-7840 + UGCACCUGGAUGUGAAAG 18 11689

SCNNlA-7841 + GUGCACCUGGAUGUGAAAG 19 11690

SCNNlA-7842 + GGUGCACCUGGAUGUGAAAG 20 11691

SCNNlA-7843 + AGGUGCACCUGGAUGUGAAAG 21 11692

SCNNlA-7844 + CAGGUGCACCUGGAUGUGAAAG 22 11693

SCNNlA-7845 + UCAGGUGCACCUGGAUGUGAAAG 23 11694

SCNNlA-7846 + CUCAGGUGCACCUGGAUGUGAAAG 24 11695

SCNNlA-7847 + UUAGCAUCUCAAUUAAAG 18 11696

SCNNlA-7848 + AUUAGCAUCUCAAUUAAAG 19 11697

SCNNlA-7849 + CAU U AGCAU CU CAAU UAAAG 20 11698

SCNNlA-7850 + UCAUUAGCAUCUCAAUUAAAG 21 11699

SCNNlA-7851 + CUCAUUAGCAUCUCAAUUAAAG 22 11700

SCNNlA-7852 + UCUCAUUAGCAUCUCAAUUAAAG 23 11701

SCNNlA-7853 + AUCUCAUUAGCAUCUCAAUUAAAG 24 11702

SCNNlA-7854 + G G C AAAG AU C U G AAC AAG 18 11703

SCNNlA-7855 + GGGCAAAGAUCUGAACAAG 19 11704

SCNNlA-7856 + GGGGCAAAGAUCUGAACAAG 20 11705

SCNNlA-7857 + AGGGGCAAAGAUCUGAACAAG 21 11706

SCNNlA-7858 + GAGGGGCAAAGAUCUGAACAAG 22 11707

SCNNlA-7859 + UGAGGGGCAAAGAUCUGAACAAG 23 11708

SCNNlA-7860 + GUGAGGGGCAAAGAUCUGAACAAG 24 11709

SCNNlA-7861 + CUAGGAGGGCAACACAAG 18 11710

SCNNlA-7862 + GCUAGGAGGGCAACACAAG 19 11711

SCNNlA-7863 + AGCUAGGAGGGCAACACAAG 20 11712

SCNNlA-7864 + CAGCUAGGAGGGCAACACAAG 21 11713

SCNNlA-7865 + ACAGCUAGGAGGGCAACACAAG 22 11714

SCNNlA-7866 + CACAGCUAGGAGGGCAACACAAG 23 11715

SCNNlA-7867 + CCACAGCUAGGAGGGCAACACAAG 24 11716

SCNNlA-7868 + UCCAGGAAGGAGAGCAAG 18 11717

SCNNlA-7869 + CUCCAGGAAGGAGAGCAAG 19 11718

SCNNlA-6140 + UCUCCAGGAAGGAGAGCAAG 20 9989

SCNNlA-7870 + GUCUCCAGGAAGGAGAGCAAG 21 11719

SCNNlA-7871 + UGUCUCCAGGAAGGAGAGCAAG 22 11720

SCNNlA-7872 + CUGUCUCCAGGAAGGAGAGCAAG 23 11721

SCNNlA-7873 + UCUGUCUCCAGGAAGGAGAGCAAG 24 11722

SCNNlA-7874 + UGCCAAGUGGUGAGCAAG 18 11723

SCNNlA-7875 + GUGCCAAGUGGUGAGCAAG 19 11724

SCNNlA-7876 + AGUGCCAAGUGGUGAGCAAG 20 11725

SCNNlA-7877 + GAGUGCCAAGUGGUGAGCAAG 21 11726

SCNNlA-7878 + GGAGUGCCAAGUGGUGAGCAAG 22 11727

SCNNlA-7879 + UGGAGUGC C A AG U G G U G AG C A AG 23 11728

SCNNlA-7880 + GUGGAGUGCCAAGUGGUGAGCAAG 24 11729

1402

5535.1 SCNNlA-7881 + AGUACUGGACCUGAGAAG 18 11730

SCNNlA-7882 + GAGUACUGGACCUGAGAAG 19 11731

SCNNlA-7883 + GGAGUACUGGACCUGAGAAG 20 11732

SCNNlA-7884 + GGGAGUACUGGACCUGAGAAG 21 11733

SCNNlA-7885 + UGGGAGUACUGGACCUGAGAAG 22 11734

SCNNlA-7886 + CUGGGAGUACUGGACCUGAGAAG 23 11735

SCNNlA-7887 + ACUGGGAGUACUGGACCUGAGAAG 24 11736

SCNNlA-7888 + GGAGUUUUCCGAAGGAAG 18 11737

SCNNlA-7889 + GGG AG U U U UCCGAAGGAAG 19 11738

SCNNlA-7890 + CGGGAGUUUUCCGAAGGAAG 20 11739

SCNNlA-7891 + CCGGGAGUUU UCCGAAGGAAG 21 11740

SCNNlA-7892 + GCCGGGAGUUUUCCGAAGGAAG 22 11741

SCNNlA-7893 + AGCCGGG AG U U U U CCGAAGGAAG 23 11742

SCNNlA-7894 + GAGCCGGGAGUUUUCCGAAGGAAG 24 11743

SCNNlA-7895 + GAGUCUGUCUCCAGGAAG 18 11744

SCNNlA-7896 + GGAGUCUGUCUCCAGGAAG 19 11745

SCNNlA-7897 + GGGAGUCUGUCUCCAGGAAG 20 11746

SCNNlA-7898 + AGGGAGUCUGUCUCCAGGAAG 21 11747

SCNNlA-7899 + AAGGGAGUCUGUCUCCAGGAAG 22 11748

SCNNlA-7900 + AAAGGGAGUCUGUCUCCAGGAAG 23 11749

SCNNlA-7901 + CAAAGGGAGUCUGUCUCCAGGAAG 24 11750

SCNNlA-7902 + GGAGGGGCCCAGGUGAAG 18 11751

SCNNlA-7903 + GGGAGGGGCCCAGGUGAAG 19 11752

SCNNlA-7904 + CGGGAGGGGCCCAGGUGAAG 20 11753

SCNNlA-7905 + CCGGGAGGGGCCCAGGUGAAG 21 11754

SCNNlA-7906 + CCCGGGAGGGGCCCAGGUGAAG 22 11755

SCNNlA-7907 + ACCCGGGAGGGGCCCAGGUGAAG 23 11756

SCNNlA-7908 + GACCCGGGAGGGGCCCAGGUGAAG 24 11757

SCNNlA-7909 + UCCUCCCCGCUCACUAAG 18 11758

SCNNlA-7910 + CUCCUCCCCGCUCACUAAG 19 11759

SCNNlA-5645 + UCUCCUCCCCGCUCACUAAG 20 9494

SCNNlA-7911 + GUCUCCUCCCCGCUCACUAAG 21 11760

SCNNlA-7912 + GGUCUCCUCCCCGCUCACUAAG 22 11761

SCNNlA-7913 + AGGUCUCCUCCCCGCUCACUAAG 23 11762

SCNNlA-7914 + CAGGUCUCCUCCCCGCUCACUAAG 24 11763

SCNNlA-7915 + GGGGAACCGGGAGGACAG 18 11764

SCNNlA-7916 + UGGGGAACCGGGAGGACAG 19 11765

SCNNlA-7917 + GUGGGGAACCGGGAGGACAG 20 11766

SCNNlA-7918 + GGUGGGGAACCGGGAGGACAG 21 11767

SCNNlA-7919 + GGGUGGGGAACCGGGAGGACAG 22 11768

SCNNlA-7920 + UGGGUGGGGAACCGGGAGGACAG 23 11769

SCNNlA-7921 + CUGGGUGGGGAACCGGGAGGACAG 24 11770

1403

5535.1 SCNNlA-7922 + GACCCGGGAGGGGCCCAG 18 11771

SCNNlA-7923 + AGACCCGGGAGGGGCCCAG 19 11772

SCNNlA-7924 + CAGACCCGGGAGGGGCCCAG 20 11773

SCNNlA-7925 + CCAGACCCGGGAGGGGCCCAG 21 11774

SCNNlA-7926 + UCCAGACCCGGGAGGGGCCCAG 22 11775

SCNNlA-7927 + GUCCAGACCCGGGAGGGGCCCAG 23 11776

SCNNlA-7928 + UGUCCAGACCCGGGAGGGGCCCAG 24 11777

SCNNlA-7929 + CUGAGUGAGUAGAGGCAG 18 11778

SCNNlA-7930 + ACUGAGUGAGUAGAGGCAG 19 11779

SCNNlA-7931 + CACUGAGUGAGUAGAGGCAG 20 11780

SCNNlA-7932 + GCACUGAGUGAGUAGAGGCAG 21 11781

SCNNlA-7933 + GGCACUGAGUGAGUAGAGGCAG 22 11782

SCNNlA-7934 + GGGCACUGAGUGAGUAGAGGCAG 23 11783

SCNNlA-7935 + GGGGCACUGAGUGAGUAGAGGCAG 24 11784

SCNNlA-7936 + GAGGGCUCCCGAGGGCAG 18 11785

SCNNlA-7937 + GGAGGGCUCCCGAGGGCAG 19 11786

SCNNlA-7938 + AGGAGGGCUCCCGAGGGCAG 20 11787

SCNNlA-7939 + AAGGAGGGCUCCCGAGGGCAG 21 11788

SCNNlA-7940 + GAAGGAGGGCUCCCGAGGGCAG 22 11789

SCNNlA-7941 + GGAAGGAGGGCUCCCGAGGGCAG 23 11790

SCNNlA-7942 + AGGAAGGAGGGCUCCCGAGGGCAG 24 11791

SCNNlA-7943 + UGGGGGACAGGAUGGCAG 18 11792

SCNNlA-7944 + CUGGGGGACAGGAUGGCAG 19 11793

SCNNlA-7945 + GCUGGGGGACAGGAUGGCAG 20 11794

SCNNlA-7946 + GGCUGGGGGACAGGAUGGCAG 21 11795

SCNNlA-7947 + AGGCUGGGGGACAGGAUGGCAG 22 11796

SCNNlA-7948 + GAGGCUGGGGGACAGGAUGGCAG 23 11797

SCNNlA-7949 + GGAGGCUGGGGGACAGGAUGGCAG 24

11798

SCNNlA-7950 + UGGGAGCAGCGCACUCAG 18 11799

SCNNlA-7951 + GUGGGAGCAGCGCACUCAG 19 11800

SCNNlA-7952 + AGUGGGAGCAGCGCACUCAG 20 11801

SCNNlA-7953 + AAGUGGGAGCAGCGCACUCAG 21 11802

SCNNlA-7954 + UAAGUGGGAGCAGCGCACUCAG 22 11803

SCNNlA-7955 + CUAAGUGGGAGCAGCGCACUCAG 23 11804

SCNNlA-7956 + ACUAAGUGGGAGCAGCGCACUCAG 24 11805

SCNNlA-7957 + CCCUCAGGCCCUGCAGAG 18 11806

SCNNlA-7958 + ACCCUCAGGCCCUGCAGAG 19 11807

SCNNlA-7959 + CACCCUCAGGCCCUGCAGAG 20 11808

SCNNlA-7960 + UCACCCUCAGGCCCUGCAGAG 21 11809

SCNNlA-7961 + CUCACCCUCAGGCCCUGCAGAG 22 11810

SCNNlA-7962 + CCUCACCCUCAGGCCCUGCAGAG 23 11811

1404

5535.1 SCNNlA-7963 + GCCUCACCCUCAGGCCCUGCAGAG 24 11812

SCNNlA-7964 + GCUGAGGAGGAGUCAGAG 18 11813

SCNNlA-7965 + GGCUGAGGAGGAGUCAGAG 19 11814

SCNNlA-7966 + GGGCUGAGGAGGAGUCAGAG 20 11815

SCNNlA-7967 + GGGGCUGAGGAGGAGUCAGAG 21 11816

SCNNlA-7968 + AGGGGCUGAGGAGGAGUCAGAG 22 11817

SCNNlA-7969 + GAGGGGCUGAGGAGGAGUCAGAG 23 11818

SCNNlA-7970 + GGAGGGGCUGAGGAGGAGUCAGAG 24

11819

SCNNlA-7971 + GCCCUGCAGAGAAGAGAG 18 11820

SCNNlA-7972 + GGCCCUGCAGAGAAGAGAG 19 11821

SCNNlA-7973 + AGGCCCUGCAGAGAAGAGAG 20 11822

SCNNlA-7974 + CAGGCCCUGCAGAGAAGAGAG 21 11823

SCNNlA-7975 + UCAGGCCCUGCAGAGAAGAGAG 22 11824

SCNNlA-7976 + CUCAGGCCCUGCAGAGAAGAGAG 23 11825

SCNNlA-7977 + CCUCAGGCCCUGCAGAGAAGAGAG 24 11826

SCNNlA-7978 + UGGUGAGCAAGGAGAGAG 18 11827

SCNNlA-7979 + GUGGUGAGCAAGGAGAGAG 19 11828

SCNNlA-6146 + AGUGGUGAGCAAGGAGAGAG 20 9995

SCNNlA-7980 + AAGUGGUGAGCAAGGAGAGAG 21 11829

SCNNlA-7981 + CAAGUGGUGAGCAAGGAGAGAG 22 11830

SCNNlA-7982 + CCAAGUGGUGAGCAAGGAGAGAG 23 11831

SCNNlA-7983 + GCCAAGUGGUGAGCAAGGAGAGAG 24 11832

SCNNlA-7984 + AAGAGGGAGACAAUAGAG 18 11833

SCNNlA-7985 + AAAGAGGGAGACAAUAGAG 19 11834

SCNNlA-5896 + GAAAGAGGGAGACAAUAGAG 20 9745

SCNNlA-7986 + AGAAAGAGGGAGACAAUAGAG 21 11835

SCNNlA-7987 + CAGAAAGAGGGAGACAAUAGAG 22 11836

SCNNlA-7988 + GCAGAAAGAGGGAGACAAUAGAG 23 11837

SCNNlA-7989 + GGCAGAAAGAGGGAGACAAUAGAG 24 11838

SCNNlA-7990 + GGAGGGCAACACAAGGAG 18 11839

SCNNlA-7991 + AGGAGGGCAACACAAGGAG 19 11840

SCNNlA-7992 + UAGGAGGGCAACACAAGGAG 20 11841

SCNNlA-7993 + CUAGGAGGGCAACACAAGGAG 21 11842

SCNNlA-7994 + GCUAGGAGGGCAACACAAGGAG 22 11843

SCNNlA-7995 + AGCUAGGAGGGCAACACAAGGAG 23 11844

SCNNlA-7996 + CAGCUAGGAGGGCAACACAAGGAG 24 11845

SCNNlA-7997 + GACAGGCCCUGGGAGGAG 18 11846

SCNNlA-7998 + AGACAGGCCCUGGGAGGAG 19 11847

SCNNlA-7999 + UAGACAGGCCCUGGGAGGAG 20 11848

SCNNlA-8000 + CUAGACAGGCCCUGGGAGGAG 21 11849

SCNNlA-8001 + CCUAGACAGGCCCUGGGAGGAG 22 11850

1405

5535.1 SCNNlA-8002 + GCCUAGACAGGCCCUGGGAGGAG 23 11851

SCNNlA-8003 + CGCCUAGACAGGCCCUGGGAGGAG 24 11852

SCNNlA-8004 + UAGAAAACAAAAUAGGAG 18 11853

SCNNlA-8005 + UUAGAAAACAAAAUAGGAG 19 11854

SCNNlA-8006 + GUUAGAAAACAAAAUAGGAG 20 11855

SCNNlA-8007 + GG U UAGAAAACAAAAUAGGAG 21 11856

SCNNlA-8008 + AGGUUAGAAAACAAAAUAGGAG 22 11857

SCNNlA-8009 + GAGGUUAGAAAACAAAAUAGGAG 23 11858

SCNNlA-8010 + UGAGGUUAGAAAACAAAAUAGGAG 24 11859

SCNNlA-8011 + GGGCCAAAAGUGCCGGAG 18 11860

SCNNlA-8012 + GGGGCCAAAAGUGCCGGAG 19 11861

SCNNlA-8013 + UGGGGCCAAAAGUGCCGGAG 20 11862

SCNNlA-8014 + UUGGGGCCAAAAGUGCCGGAG 21 11863

SCNNlA-8015 + GUUGGGGCCAAAAGUGCCGGAG 22 11864

SCNNlA-8016 + AGUUGGGGCCAAAAGUGCCGGAG 23 11865

SCNNlA-8017 + GAGUUGGGGCCAAAAGUGCCGGAG 24 11866

SCNNlA-8018 + CCAGCAGACCUGCGGGAG 18 11867

SCNNlA-8019 + GCCAGCAGACCUGCGGGAG 19 11868

SCNNlA-8020 + AGCCAGCAGACCUGCGGGAG 20 11869

SCNNlA-8021 + GAGCCAGCAGACCUGCGGGAG 21 11870

SCNNlA-8022 + GGAGCCAGCAGACCUGCGGGAG 22 11871

SCNNlA-8023 + UGGAGCCAGCAGACCUGCGGGAG 23 11872

SCNNlA-8024 + CUGGAGCCAGCAGACCUGCGGGAG 24 11873

SCNNlA-8025 + CUAGACAGGCCCUGGGAG 18 11874

SCNNlA-8026 + CCUAGACAGGCCCUGGGAG 19 11875

SCNNlA-8027 + GCCUAGACAGGCCCUGGGAG 20 11876

SCNNlA-8028 + CGCCUAGACAGGCCCUGGGAG 21 11877

SCNNlA-8029 + ACGCCUAGACAGGCCCUGGGAG 22 11878

SCNNlA-8030 + CACGCCUAGACAGGCCCUGGGAG 23 11879

SCNNlA-8031 + ACACGCCUAGACAGGCCCUGGGAG 24 11880

SCNNlA-8032 + AGAGAGAUAGGGAUGGAG 18 11881

SCNNlA-8033 + CAGAGAGAUAGGGAUGGAG 19 11882

SCNNlA-8034 + ACAGAGAGAUAGGGAUGGAG 20 11883

SCNNlA-8035 + GACAGAGAGAUAGGGAUGGAG 21 11884

SCNNlA-8036 + GGACAGAGAGAUAGGGAUGGAG 22 11885

SCNNlA-8037 + AGGACAGAGAGAUAGGGAUGGAG 23 11886

SCNNlA-8038 + AAGGACAGAGAGAUAGGGAUGGAG 24 11887

SCNNlA-8039 + GCGGGGGGAGGGGCUGAG 18 11888

SCNNlA-8040 + GGCGGGGGGAGGGGCUGAG 19 11889

SCNNlA-8041 + GGGCGGGGGGAGGGGCUGAG 20 11890

SCNNlA-8042 + AGGGCGGGGGGAGGGGCUGAG 21 11891

SCNNlA-8043 + CAGGGCGGGGGGAGGGGCUGAG 22 11892

1406

5535.1 SCNNlA-8044 + GCAGGGCGGGGGGAGGGGCUGAG 23 11893

SCNNlA-8045 + AGCAGGGCGGGGGGAGGGGCUGAG 24

11894

SCNNlA-8046 + GGAGGGGCACUGAGUGAG 18 11895

SCNNlA-8047 + AGGAGGGGCACUGAGUGAG 19 11896

SCNNlA-8048 + GAGGAGGGGCACUGAGUGAG 20 11897

SCNNlA-8049 + GGAGGAGGGGCACUGAGUGAG 21 11898

SCNNlA-8050 + UGGAGGAGGGGCACUGAGUGAG 22 11899

SCNNlA-8051 + AUGGAGGAGGGGCACUGAGUGAG 23 11900

SCNNlA-8052 + GAUGGAGGAGGGGCACUGAGUGAG 24

11901

SCNNlA-8053 + AUCUCAAUUAAAGGUGAG 18 11902

SCNNlA-8054 + CAUCUCAAUUAAAGGUGAG 19 11903

SCNNlA-8055 + GCAUCUCAAUUAAAGGUGAG 20 11904

SCNNlA-8056 + AGCAUCUCAAUUAAAGGUGAG 21 11905

SCNNlA-8057 + UAGCAUCUCAAUUAAAGGUGAG 22 11906

SCNNlA-8058 + UUAGCAUCUCAAUUAAAGGUGAG 23 11907

SCNNlA-8059 + AUUAGCAUCUCAAUUAAAGGUGAG 24 11908

SCNNlA-8060 + AGUGGUGGGGGCAAAUAG 18 11909

SCNNlA-8061 + CAGUGGUGGGGGCAAAUAG 19 11910

SCNNlA-8062 + GCAGUGGUGGGGGCAAAUAG 20 11911

SCNNlA-8063 + GGCAGUGGUGGGGGCAAAUAG 21 11912

SCNNlA-8064 + GGGCAGUGGUGGGGGCAAAUAG 22 11913

SCNNlA-8065 + GGGGCAGUGGUGGGGGCAAAUAG 23 11914

SCNNlA-8066 + GGGGGCAGUGGUGGGGGCAAAUAG 24

11915

SCNNlA-8067 + UCCUGAGCCCACAGCUAG 18 11916

SCNNlA-8068 + AUCCUGAGCCCACAGCUAG 19 11917

SCNNlA-8069 + GAUCCUGAGCCCACAGCUAG 20 11918

SCNNlA-8070 + GGAUCCUGAGCCCACAGCUAG 21 11919

SCNNlA-8071 + AGGAUCCUGAGCCCACAGCUAG 22 11920

SCNNlA-8072 + AAGGAUCCUGAGCCCACAGCUAG 23 11921

SCNNlA-8073 + GAAGGAUCCUGAGCCCACAGCUAG 24 11922

SCNNlA-8074 + AUAAGAGCCAAGGGCUAG 18 11923

SCNNlA-8075 + CAUAAGAGCCAAGGGCUAG 19 11924

SCNNlA-5662 + ACAUAAGAGCCAAGGGCUAG 20 9511

SCNNlA-8076 + GACAUAAGAGCCAAGGGCUAG 21 11925

SCNNlA-8077 + AGACAUAAGAGCCAAGGGCUAG 22 11926

SCNNlA-8078 + AAGACAUAAGAGCCAAGGGCUAG 23 11927

SCNNlA-8079 + UAAGACAUAAGAGCCAAGGGCUAG 24 11928

SCNNlA-8080 + GGUGAAGCUGGGGGCUAG 18 11929

SCNNlA-8081 + AGGUGAAGCUGGGGGCUAG 19 11930

1407

5535.1 SCNNlA-8082 + CAGGUGAAGCUGGGGGCUAG 20 11931

SCNNlA-8083 + CCAGGUGAAGCUGGGGGCUAG 21 11932

SCNNlA-8084 + CCCAGGUGAAGCUGGGGGCUAG 22 11933

SCNNlA-8085 + GCCCAGGUGAAGCUGGGGGCUAG 23 11934

SCNNlA-8086 + GGCCCAGGUGAAGCUGGGGGCUAG 24 11935

SCNNlA-8087 + GGCAGCGCGAGGGCCACG 18 11936

SCNNlA-8088 + AGGCAGCGCGAGGGCCACG 19 11937

SCNNlA-8089 + GAGGCAGCGCGAGGGCCACG 20 11938

SCNNlA-8090 + AGAGGCAGCGCGAGGGCCACG 21 11939

SCNNlA-8091 + CAGAGGCAGCGCGAGGGCCACG 22 11940

SCNNlA-8092 + CCAGAGGCAGCGCGAGGGCCACG 23 11941

SCNNlA-8093 + ACCAGAGGCAGCGCGAGGGCCACG 24 11942

SCNNlA-8094 + GAGCAUUGAUACACACCG 18 11943

SCNNlA-8095 + UGAGCAUUGAUACACACCG 19 11944

SCNNlA-5665 + CUGAGCAUUGAUACACACCG 20 9514

SCNNlA-8096 + CCUGAGCAUUGAUACACACCG 21 11945

SCNNlA-8097 + GCCUGAGCAUUGAUACACACCG 22 11946

SCNNlA-8098 + AGCCUGAGCAUUGAUACACACCG 23 11947

SCNNlA-8099 + CAGCCUGAGCAUUGAUACACACCG 24 11948

SCNNlA-8100 + AGAGCCGGGAGUUUUCCG 18 11949

SCNNlA-8101 + CAGAGCCGGGAGUUUUCCG 19 11950

SCNNlA-8102 + UCAGAGCCGGGAGUUUUCCG 20 11951

SCNNlA-8103 + GUCAGAGCCGGGAGUUUUCCG 21 11952

SCNNlA-8104 + AGUCAGAGCCGGGAGUUUUCCG 22 11953

SCNNlA-8105 + GAG U CAG AGCCGGG AG U U U U CCG 23 11954

SCNNlA-8106 + GGAGUCAGAGCCGGGAGUUUUCCG 24 11955

SCNNlA-8107 + CAAUAGAGAGGGACAGCG 18 11956

SCNNlA-8108 + ACAAUAGAGAGGGACAGCG 19 11957

SCNNlA-8109 + GACAAUAGAGAGGGACAGCG 20 11958

SCNNlA-8110 + AGACAAUAGAGAGGGACAGCG 21 11959

SCNNlA-8111 + GAGACAAUAGAGAGGGACAGCG 22 11960

SCNNlA-8112 + GGAGACAAUAGAGAGGGACAGCG 23 11961

SCNNlA-8113 + GGGAGACAAUAGAGAGGGACAGCG 24 11962

SCNNlA-8114 + GGGAGGAUGUGGCCAGCG 18 11963

SCNNlA-8115 + AGGGAGGAUGUGGCCAGCG 19 11964

SCNNlA-8116 + CAGGGAGGAUGUGGCCAGCG 20 11965

SCNNlA-8117 + GCAGGGAGGAUGUGGCCAGCG 21 11966

SCNNlA-8118 + UGCAGGGAGGAUGUGGCCAGCG 22 11967

SCNNlA-8119 + GUGCAGGGAGGAUGUGGCCAGCG 23 11968

SCNNlA-8120 + GGUGCAGGGAGGAUGUGGCCAGCG 24 11969

SCNNlA-8121 + UUAAAGGUGAGCAGGGCG 18 11970

SCNNlA-8122 + AUUAAAGGUGAGCAGGGCG 19 11971

1408

5535.1 SCNNlA-5669 + A A U U A A AG GUGAGCAGGGCG 20 9518

SCNNlA-8123 + CAAUUAAAGGUGAGCAGGGCG 21 11972

SCNNlA-8124 + UCAAUUAAAGGUGAGCAGGGCG 22 11973

SCNNlA-8125 + CUCAAUUAAAGGUGAGCAGGGCG 23 11974

SCNNlA-8126 + UCUCAAUUAAAGGUGAGCAGGGCG 24 11975

SCNNlA-8127 + UGGCCAGCGCUGGAAAGG 18 11976

SCNNlA-8128 + GUGGCCAGCGCUGGAAAGG 19 11977

SCNNlA-8129 + UGUGGCCAGCGCUGGAAAGG 20 11978

SCNNlA-8130 + AUGUGGCCAGCGCUGGAAAGG 21 11979

SCNNlA-8131 + GAUGUGGCCAGCGCUGGAAAGG 22 11980

SCNNlA-8132 + GGAUGUGGCCAGCGCUGGAAAGG 23 11981

SCNNlA-8133 + AGGAUGUGGCCAGCGCUGGAAAGG 24 11982

SCNNlA-8134 + CCAGGAAGGAGAGCAAGG 18 11983

SCNNlA-8135 + UCCAGGAAGGAGAGCAAGG 19 11984

SCNNlA-6151 + CUCCAGGAAGGAGAGCAAGG 20 10000

SCNNlA-8136 + UCUCCAGGAAGGAGAGCAAGG 21 11985

SCNNlA-8137 + GUCUCCAGGAAGGAGAGCAAGG 22 11986

SCNNlA-8138 + UGUCUCCAGGAAGGAGAGCAAGG 23 11987

SCNNlA-8139 + CUGUCUCCAGGAAGGAGAGCAAGG 24 11988

SCNNlA-1604 + CAAGGGUCAGGGUCAAGG 18 5453

SCNNlA-1605 + GCAAGGGUCAGGGUCAAGG 19 5454

SCNNlA-1606 + AGCAAGGGUCAGGGUCAAGG 20 5455

SCNNlA-1607 + GAGCAAGGGUCAGGGUCAAGG 21 5456

SCNNlA-1608 + AGAGCAAGGGUCAGGGUCAAGG 22 5457

SCNNlA-1609 + GAGAGCAAGGGUCAGGGUCAAGG 23 5458

SCNNlA-1610 + GGAGAGCAAGGGUCAGGGUCAAGG 24 5459

SCNNlA-8140 + CCGGGAGUUUUCCGAAGG 18 11989

SCNNlA-8141 + GCCGGGAGUUUUCCGAAGG 19 11990

SCNNlA-8142 + AGCCGGGAGUUUUCCGAAGG 20 11991

SCNNlA-8143 + GAGCCGGGAGUUUUCCGAAGG 21 11992

SCNNlA-8144 + AGAGCCGGGAGUUUUCCGAAGG 22 11993

SCNNlA-8145 + CAG AG CCGGG AG U U U UCCGAAGG 23 11994

SCNNlA-8146 + UCAGAGCCGGGAGUUUUCCGAAGG 24 11995

SCNNlA-8147 + ACAGACCCGGAGCCCAGG 18 11996

SCNNlA-8148 + CACAGACCCGGAGCCCAGG 19 11997

SCNNlA-8149 + ACACAGACCCGGAGCCCAGG 20 11998

SCNNlA-8150 + GACACAGACCCGGAGCCCAGG 21 11999

SCNNlA-8151 + GGACACAGACCCGGAGCCCAGG 22 12000

SCNNlA-8152 + UGGACACAGACCCGGAGCCCAGG 23 12001

SCNNlA-8153 + GUGGACACAGACCCGGAGCCCAGG 24 12002

SCNNlA-8154 + GAGAAGGGGCCAGCCAGG 18 12003

SCNNlA-8155 + GGAGAAGGGGCCAGCCAGG 19 12004

1409

5535.1 SCNNlA-8156 + AGGAGAAGGGGCCAGCCAGG 20 12005

SCNNlA-8157 + AAGGAGAAGGGGCCAGCCAGG 21 12006

SCNNlA-8158 + CAAGGAGAAGGGGCCAGCCAGG 22 12007

SCNNlA-8159 + ACAAGGAGAAGGGGCCAGCCAGG 23 12008

SCNNlA-8160 + CACAAGGAGAAGGGGCCAGCCAGG 24 12009

SCNNlA-8161 + AGGGAGUCUGUCUCCAGG 18 12010

SCNNlA-8162 + AAGGGAGUCUGUCUCCAGG 19 12011

SCNNlA-8163 + AAAGGGAGUCUGUCUCCAGG 20 12012

SCNNlA-8164 + CAAAGGGAGUCUGUCUCCAGG 21 12013

SCNNlA-8165 + CCAAAGGGAGUCUGUCUCCAGG 22 12014

SCNNlA-8166 + ACCAAAGGGAGUCUGUCUCCAGG 23 12015

SCNNlA-8167 + CACCAAAGGGAGUCUGUCUCCAGG 24 12016

SCNNlA-8168 + C A A U U A A AG GUGAGCAGG 18 12017

SCNNlA-8169 + UCAAUUAAAGGUGAGCAGG 19 12018

SCNNlA-8170 + CUCAAUUAAAGGUGAGCAGG 20 12019

SCNNlA-8171 + UCUCAAUUAAAGGUGAGCAGG 21 12020

SCNNlA-8172 + AUCUCAAUUAAAGGUGAGCAGG 22 12021

SCNNlA-8173 + CAUCUCAAUUAAAGGUGAGCAGG 23 12022

SCNNlA-8174 + GCAUCUCAAUUAAAGGUGAGCAGG 24 12023

SCNNlA-8175 + UGAGUGAGUAGAGGCAGG 18 12024

SCNNlA-8176 + CUGAGUGAGUAGAGGCAGG 19 12025

SCNNlA-5677 + ACUGAGUGAGUAGAGGCAGG 20 9526

SCNNlA-8177 + CACUGAGUGAGUAGAGGCAGG 21 12026

SCNNlA-8178 + GCACUGAGUGAGUAGAGGCAGG 22 12027

SCNNlA-8179 + GGCACUGAGUGAGUAGAGGCAGG 23 12028

SCNNlA-8180 + GGGCACUGAGUGAGUAGAGGCAGG 24 12029

SCNNlA-8181 + GCGCUGGAAAGGAAGAGG 18 12030

SCNNlA-8182 + AGCGCUGGAAAGGAAGAGG 19 12031

SCNNlA-8183 + CAGCGCUGGAAAGGAAGAGG 20 12032

SCNNlA-8184 + CCAGCGCUGGAAAGGAAGAGG 21 12033

SCNNlA-8185 + GCCAGCGCUGGAAAGGAAGAGG 22 12034

SCNNlA-8186 + GGCCAGCGCUGGAAAGGAAGAGG 23 12035

SCNNlA-8187 + UGGCCAGCGCUGGAAAGGAAGAGG 24 12036

SCNNlA-8188 + CCGGAGCCCAGGAAGAGG 18 12037

SCNNlA-8189 + CCCGGAGCCCAGGAAGAGG 19 12038

SCNNlA-8190 + ACCCGGAGCCCAGGAAGAGG 20 12039

SCNNlA-8191 + GACCCGGAGCCCAGGAAGAGG 21 12040

SCNNlA-8192 + AGACCCGGAGCCCAGGAAGAGG 22 12041

SCNNlA-8193 + CAGACCCGGAGCCCAGGAAGAGG 23 12042

SCNNlA-8194 + ACAGACCCGGAGCCCAGGAAGAGG 24 12043

SCNNlA-8195 + CGCAGACAGGCAAGGAGG 18 12044

SCNNlA-8196 + ACGCAGACAGGCAAGGAGG 19 12045

1410

5535.1 SCNNlA-8197 + GACGCAGACAGGCAAGGAGG 20 12046

SCNNlA-8198 + AGACGCAGACAGGCAAGGAGG 21 12047

SCNNlA-8199 + UAGACGCAGACAGGCAAGGAGG 22 12048

SCNNlA-8200 + UUAGACGCAGACAGGCAAGGAGG 23 12049

SCNNlA-8201 + UUUAGACGCAGACAGGCAAGGAGG 24 12050

SCNNlA-8202 + UAGACAGGCCCUGGGAGG 18 12051

SCNNlA-8203 + CUAGACAGGCCCUGGGAGG 19 12052

SCNNlA-6157 + CCUAGACAGGCCCUGGGAGG 20 10006

SCNNlA-8204 + GCCUAGACAGGCCCUGGGAGG 21 12053

SCNNlA-8205 + CGCCUAGACAGGCCCUGGGAGG 22 12054

SCNNlA-8206 + ACGCCUAGACAGGCCCUGGGAGG 23 12055

SCNNlA-8207 + CACGCCUAGACAGGCCCUGGGAGG 24 12056

SCNNlA-8208 + GAGAGAUAGGGAUGGAGG 18 12057

SCNNlA-8209 + AGAGAGAUAGGGAUGGAGG 19 12058

SCNNlA-6158 + CAGAGAGAUAGGGAUGGAGG 20 10007

SCNNlA-8210 + ACAGAGAGAUAGGGAUGGAGG 21 12059

SCNNlA-8211 + GACAGAGAGAUAGGGAUGGAGG 22 12060

SCNNlA-8212 + GGACAGAGAGAUAGGGAUGGAGG 23 12061

SCNNlA-8213 + AGGACAGAGAGAUAGGGAUGGAGG 24

12062

SCNNlA-8214 + GUGAAGCUGGGGGCUAGG 18 12063

SCNNlA-8215 + GGUGAAGCUGGGGGCUAGG 19 12064

SCNNlA-5681 + AGGUGAAGCUGGGGGCUAGG 20 9530

SCNNlA-8216 + CAGGUGAAGCUGGGGGCUAGG 21 12065

SCNNlA-8217 + CCAGGUGAAGCUGGGGGCUAGG 22 12066

SCNNlA-8218 + CCCAGGUGAAGCUGGGGGCUAGG 23 12067

SCNNlA-8219 + GCCCAGGUGAAGCUGGGGGCUAGG 24 12068

SCNNlA-8220 + GCCUGGGUGGGGAACCGG 18 12069

SCNNlA-8221 + GGCCUGGGUGGGGAACCGG 19 12070

SCNNlA-8222 + GGGCCUGGGUGGGGAACCGG 20 12071

SCNNlA-8223 + AGGGCCUGGGUGGGGAACCGG 21 12072

SCNNlA-8224 + GAGGGCCUGGGUGGGGAACCGG 22 12073

SCNNlA-8225 + AGAGGGCCUGGGUGGGGAACCGG 23 12074

SCNNlA-8226 + GAGAGGGCCUGGGUGGGGAACCGG 24 12075

SCNNlA-8227 + AGCAUUGAUACACACCGG 18 12076

SCNNlA-8228 + GAGCAUUGAUACACACCGG 19 12077

SCNNlA-5682 + UGAGCAUUGAUACACACCGG 20 9531

SCNNlA-8229 + CUGAGCAUUGAUACACACCGG 21 12078

SCNNlA-8230 + CCUGAGCAUUGAUACACACCGG 22 12079

SCNNlA-8231 + GCCUGAGCAUUGAUACACACCGG 23 12080

SCNNlA-8232 + AGCCUGAGCAUUGAUACACACCGG 24 12081

SCNNlA-8233 + AACCUUGUCCAGACCCGG 18 12082

1411

5535.1 SCNNlA-8234 + CAACCUUGUCCAGACCCGG 19 12083

SCNNlA-8235 + CCAACCUUGUCCAGACCCGG 20 12084

SCNNlA-8236 + UCCAACCUUGUCCAGACCCGG 21 12085

SCNNlA-8237 + CUCCAACCUUGUCCAGACCCGG 22 12086

SCNNlA-8238 + CCUCCAACCUUGUCCAGACCCGG 23 12087

SCNNlA-8239 + CCCUCCAACCUUGUCCAGACCCGG 24 12088

SCNNlA-8240 + CCCAGGCCCUGCACGCGG 18 12089

SCNNlA-8241 + ACCCAGGCCCUGCACGCGG 19 12090

SCNNlA-8242 + AACCCAGGCCCUGCACGCGG 20 12091

SCNNlA-8243 + CAACCCAGGCCCUGCACGCGG 21 12092

SCNNlA-8244 + ACAACCCAGGCCCUGCACGCGG 22 12093

SCNNlA-8245 + CACAACCCAGGCCCUGCACGCGG 23 12094

SCNNlA-8246 + ACACAACCCAGGCCCUGCACGCGG 24 12095

SCNNlA-8247 + UAAAGGUGAGCAGGGCGG 18 12096

SCNNlA-8248 + UUAAAGGUGAGCAGGGCGG 19 12097

SCNNlA-5683 + AUUAAAGGUGAGCAGGGCGG 20 9532

SCNNlA-8249 + AAUUAAAGGUGAGCAGGGCGG 21 12098

SCNNlA-8250 + CAAUUAAAGGUGAGCAGGGCGG 22 12099

SCNNlA-8251 + UCAAUUAAAGGUGAGCAGGGCGG 23 12100

SCNNlA-8252 + CUCAAUUAAAGGUGAGCAGGGCGG 24 12101

SCNNlA-8253 + CCCACUCCCAGGUUGCGG 18 12102

SCNNlA-8254 + UCCCACUCCCAGGUUGCGG 19 12103

SCNNlA-8255 + UUCCCACUCCCAGGUUGCGG 20 12104

SCNNlA-8256 + CUUCCCACUCCCAGGUUGCGG 21 12105

SCNNlA-8257 + GCUUCCCACUCCCAGGUUGCGG 22 12106

SCNNlA-8258 + AGCUUCCCACUCCCAGGUUGCGG 23 12107

SCNNlA-8259 + CAGCUUCCCACUCCCAGGUUGCGG 24 12108

SCNNlA-8260 + GGGCUGGAGGAGACUCGG 18 12109

SCNNlA-8261 + AGGGCUGGAGGAGACUCGG 19 12110

SCNNlA-8262 + AAGGGCUGGAGGAGACUCGG 20 12111

SCNNlA-8263 + AAAGGGCUGGAGGAGACUCGG 21 12112

SCNNlA-8264 + AAAAGGGCUGGAGGAGACUCGG 22 12113

SCNNlA-8265 + AAAAAGGGCUGGAGGAGACUCGG 23 12114

SCNNlA-8266 + CAAAAAGGGCUGGAGGAGACUCGG 24 12115

SCNNlA-8267 + AAUCAGACCCAAAAAGGG 18 12116

SCNNlA-8268 + GAAUCAGACCCAAAAAGGG 19 12117

SCNNlA-8269 + AGAAUCAGACCCAAAAAGGG 20 12118

SCNNlA-8270 + GAGAAUCAGACCCAAAAAGGG 21 12119

SCNNlA-8271 + AGAGAAUCAGACCCAAAAAGGG 22 12120

SCNNlA-8272 + CAGAGAAUCAGACCCAAAAAGGG 23 12121

SCNNlA-8273 + UCAGAGAAUCAGACCCAAAAAGGG 24 12122

SCNNlA-8274 + CCCGCUGGCCGGCCAGGG 18 12123

1412

5535.1 SCNNlA-8275 + GCCCGCUGGCCGGCCAGGG 19 12124

SCNNlA-8276 + CGCCCGCUGGCCGGCCAGGG 20 12125

SCNNlA-8277 + CCGCCCGCUGGCCGGCCAGGG 21 12126

SCNNlA-8278 + CCCGCCCGCUGGCCGGCCAGGG 22 12127

SCNNlA-8279 + GCCCGCCCGCUGGCCGGCCAGGG 23 12128

SCNNlA-8280 + AGCCCGCCCGCUGGCCGGCCAGGG 24 12129

SCNNlA-8281 + AAUUAAAGGUGAGCAGGG 18 12130

SCNNlA-8282 + C A A U U A A AG GUGAGCAGGG 19 12131

SCNNlA-6160 + UCAAUUAAAGGUGAGCAGGG 20 10009

SCNNlA-8283 + CUCAAUUAAAGGUGAGCAGGG 21 12132

SCNNlA-8284 + UCUCAAUUAAAGGUGAGCAGGG 22 12133

SCNNlA-8285 + AUCUCAAUUAAAGGUGAGCAGGG 23 12134

SCNNlA-8286 + CAUCUCAAUUAAAGGUGAGCAGGG 24 12135

SCNNlA-8287 + ACCGGGAGGACAGGAGGG 18 12136

SCNNlA-8288 + AACCGGGAGGACAGGAGGG 19 12137

SCNNlA-8289 + GAACCGGGAGGACAGGAGGG 20 12138

SCNNlA-8290 + GGAACCGGGAGGACAGGAGGG 21 12139

SCNNlA-8291 + GGGAACCGGGAGGACAGGAGGG 22 12140

SCNNlA-8292 + GGGGAACCGGGAGGACAGGAGGG 23 12141

SCNNlA-8293 + UGGGGAACCGGGAGGACAGGAGGG 24 12142

SCNNlA-8294 + AAGGACAGAGAGAUAGGG 18 12143

SCNNlA-8295 + GAAGGACAGAGAGAUAGGG 19 12144

SCNNlA-8296 + CGAAGGACAGAGAGAUAGGG 20 12145

SCNNlA-8297 + GCGAAGGACAGAGAGAUAGGG 21 12146

SCNNlA-8298 + AGCGAAGGACAGAGAGAUAGGG 22 12147

SCNNlA-8299 + CAGCGAAGGACAGAGAGAUAGGG 23 12148

SCNNlA-8300 + ACAGCGAAGGACAGAGAGAUAGGG 24 12149

SCNNlA-8301 + ACCUUGUCCAGACCCGGG 18 12150

SCNNlA-8302 + AACCUUGUCCAGACCCGGG 19 12151

SCNNlA-5686 + CAACCUUGUCCAGACCCGGG 20 9535

SCNNlA-8303 + CCAACCUUGUCCAGACCCGGG 21 12152

SCNNlA-8304 + UCCAACCUUGUCCAGACCCGGG 22 12153

SCNNlA-8305 + CUCCAACCUUGUCCAGACCCGGG 23 12154

SCNNlA-8306 + CCUCCAACCUUGUCCAGACCCGGG 24 12155

SCNNlA-8307 + AAAGGUGAGCAGGGCGGG 18 12156

SCNNlA-8308 + UAAAGGUGAGCAGGGCGGG 19 12157

SCNNlA-5688 + UUAAAGGUGAGCAGGGCGGG 20 9537

SCNNlA-8309 + AUUAAAGGUGAGCAGGGCGGG 21 12158

SCNNlA-8310 + AAUUAAAGGUGAGCAGGGCGGG 22 12159

SCNNlA-8311 + CAAUUAAAGGUGAGCAGGGCGGG 23 12160

SCNNlA-8312 + UCAAUUAAAGGUGAGCAGGGCGGG 24 12161

SCNNlA-8313 + GCAGGGCGGGGGGAGGGG 18 12162

1413

5535.1 SCNNlA-8314 + AGCAGGGCGGGGGGAGGGG 19 12163

SCNNlA-8315 + GAGCAGGGCGGGGGGAGGGG 20 12164

SCNNlA-8316 + UGAGCAGGGCGGGGGGAGGGG 21 12165

SCNNlA-8317 + GUGAGCAGGGCGGGGGGAGGGG 22 12166

SCNNlA-8318 + GGUGAGCAGGGCGGGGGGAGGGG 23 12167

SCNNlA-8319 + AGGUGAGCAGGGCGGGGGGAGGGG 24

12168

SCNNlA-8320 + CAUUGAUACACACCGGGG 18 12169

SCNNlA-8321 + GCAUUGAUACACACCGGGG 19 12170

SCNNlA-8322 + AGCAUUGAUACACACCGGGG 20 12171

SCNNlA-8323 + GAGCAUUGAUACACACCGGGG 21 12172

SCNNlA-8324 + UGAGCAUUGAUACACACCGGGG 22 12173

SCNNlA-8325 + CUGAGCAUUGAUACACACCGGGG 23 12174

SCNNlA-8326 + CCUGAGCAUUGAUACACACCGGGG 24 12175

SCNNlA-8327 + AUUGAUACACACCGGGGG 18 12176

SCNNlA-8328 + CAUUGAUACACACCGGGGG 19 12177

SCNNlA-5265 + GCAUUGAUACACACCGGGGG 20 9114

SCNNlA-8329 + AGCAUUGAUACACACCGGGGG 21 12178

SCNNlA-8330 + GAGCAUUGAUACACACCGGGGG 22 12179

SCNNlA-8331 + UGAGCAUUGAUACACACCGGGGG 23 12180

SCNNlA-8332 + CUGAGCAUUGAUACACACCGGGGG 24 12181

SCNNlA-8333 + AGGUGAGCAGGGCGGGGG 18 12182

SCNNlA-8334 + AAGGUGAGCAGGGCGGGGG 19 12183

SCNNlA-8335 + AAAGGUGAGCAGGGCGGGGG 20 12184

SCNNlA-8336 + UAAAGGUGAGCAGGGCGGGGG 21 12185

SCNNlA-8337 + UUAAAGGUGAGCAGGGCGGGGG 22 12186

SCNNlA-8338 + AUUAAAGGUGAGCAGGGCGGGGG 23 12187

SCNNlA-8339 + AAUUAAAGGUGAGCAGGGCGGGGG 24

12188

SCNNlA-8340 + GGUGAGCAGGGCGGGGGG 18 12189

SCNNlA-8341 + AGGUGAGCAGGGCGGGGGG 19 12190

SCNNlA-6164 + AAGGUGAGCAGGGCGGGGGG 20 10013

SCNNlA-8342 + AAAGGUGAGCAGGGCGGGGGG 21 12191

SCNNlA-8343 + UAAAGGUGAGCAGGGCGGGGGG 22 12192

SCNNlA-8344 + UUAAAGGUGAGCAGGGCGGGGGG 23 12193

SCNNlA-8345 + AUUAAAGGUGAGCAGGGCGGGGGG 24

12194

SCNNlA-8346 + GCCUAGACAGGCCCUGGG 18 12195

SCNNlA-8347 + CGCCUAGACAGGCCCUGGG 19 12196

SCNNlA-5691 + ACGCCUAGACAGGCCCUGGG 20 9540

SCNNlA-8348 + CACGCCUAGACAGGCCCUGGG 21 12197

SCNNlA-8349 + ACACGCCUAGACAGGCCCUGGG 22 12198

1414

5535.1 SCNNlA-8350 + CACACGCCUAGACAGGCCCUGGG 23 12199

SCNNlA-8351 + GCACACGCCUAGACAGGCCCUGGG 24 12200

SCNNlA-8352 + AGGCUGAGAGGGCCUGGG 18 12201

SCNNlA-8353 + CAGGCUGAGAGGGCCUGGG 19 12202

SCNNlA-6165 + CCAGGCUGAGAGGGCCUGGG 20 10014

SCNNlA-8354 + GCCAGGCUGAGAGGGCCUGGG 21 12203

SCNNlA-8355 + AGCCAGGCUGAGAGGGCCUGGG 22 12204

SCNNlA-8356 + CAGCCAGGCUGAGAGGGCCUGGG 23 12205

SCNNlA-8357 + CCAGCCAGGCUGAGAGGGCCUGGG 24 12206

SCNNlA-8358 + GAGAAGGCGGACUCUGGG 18 12207

SCNNlA-8359 + UGAGAAGGCGGACUCUGGG 19 12208

SCNNlA-8360 + CUGAGAAGGCGGACUCUGGG 20 12209

SCNNlA-8361 + CCUGAGAAGGCGGACUCUGGG 21 12210

SCNNlA-8362 + ACCUGAGAAGGCGGACUCUGGG 22 12211

SCNNlA-8363 + GACCUGAGAAGGCGGACUCUGGG 23 12212

SCNNlA-8364 + GGACCUGAGAAGGCGGACUCUGGG 24 12213

SCNNlA-1623 + GCCCCGGAGUGGAUUGGG 18 5472

SCNNlA-1624 + AGCCCCGGAGUGGAUUGGG 19 5473

SCNNlA-1625 + GAGCCCCGGAGUGGAUUGGG 20 5474

SCNNlA-1626 + UGAGCCCCGGAGUGGAUUGGG 21 5475

SCNNlA-1627 + AUGAGCCCCGGAGUGGAUUGGG 22 5476

SCNNlA-1628 + CAUGAGCCCCGGAGUGGAUUGGG 23 5477

SCNNlA-1629 + UCAUGAGCCCCGGAGUGGAUUGGG 24 5478

SCNNlA-8365 + ACAGAGAGAUAGGGAUGG 18 12214

SCNNlA-8366 + GACAGAGAGAUAGGGAUGG 19 12215

SCNNlA-5915 + GGACAGAGAGAUAGGGAUGG 20 9764

SCNNlA-8367 + AGGACAGAGAGAUAGGGAUGG 21 12216

SCNNlA-8368 + AAGGACAGAGAGAUAGGGAUGG 22 12217

SCNNlA-8369 + GAAGGACAGAGAGAUAGGGAUGG 23 12218

SCNNlA-8370 + CGAAGGACAGAGAGAUAGGGAUGG 24 12219

SCNNlA-8371 + CGCCUAGACAGGCCCUGG 18 12220

SCNNlA-8372 + ACGCCUAGACAGGCCCUGG 19 12221

SCNNlA-8373 + CACGCCUAGACAGGCCCUGG 20 12222

SCNNlA-8374 + ACACGCCUAGACAGGCCCUGG 21 12223

SCNNlA-8375 + CACACGCCUAGACAGGCCCUGG 22 12224

SCNNlA-8376 + GCACACGCCUAGACAGGCCCUGG 23 12225

SCNNlA-8377 + GGCACACGCCUAGACAGGCCCUGG 24 12226

SCNNlA-8378 + ACAGGUGCAGCGGCCUGG 18 12227

SCNNlA-8379 + GACAGGUGCAGCGGCCUGG 19 12228

SCNNlA-8380 + UGACAGGUGCAGCGGCCUGG 20 12229

SCNNlA-8381 + CUGACAGGUGCAGCGGCCUGG 21 12230

SCNNlA-8382 + CCUGACAGGUGCAGCGGCCUGG 22 12231

1415

5535.1 SCNNlA-8383 + ACCUGACAGGUGCAGCGGCCUGG 23 12232

SCNNlA-8384 + CACCUGACAGGUGCAGCGGCCUGG 24 12233

SCNNlA-8385 + CAGGCUGAGAGGGCCUGG 18 12234

SCNNlA-8386 + CCAGGCUGAGAGGGCCUGG 19 12235

SCNNlA-8387 + GCCAGGCUGAGAGGGCCUGG 20 12236

SCNNlA-8388 + AGCCAGGCUGAGAGGGCCUGG 21 12237

SCNNlA-8389 + CAGCCAGGCUGAGAGGGCCUGG 22 12238

SCNNlA-8390 + CCAGCCAGGCUGAGAGGGCCUGG 23 12239

SCNNlA-8391 + GCCAGCCAGGCUGAGAGGGCCUGG 24 12240

SCNNlA-8392 + AGACCCAAAAAGGGCUGG 18 12241

SCNNlA-8393 + CAGACCCAAAAAGGGCUGG 19 12242

SCNNlA-5694 + UCAGACCCAAAAAGGGCUGG 20 9543

SCNNlA-8394 + AUCAGACCCAAAAAGGGCUGG 21 12243

SCNNlA-8395 + AAUCAGACCCAAAAAGGGCUGG 22 12244

SCNNlA-8396 + GAAUCAGACCCAAAAAGGGCUGG 23 12245

SCNNlA-8397 + AGAAUCAGACCCAAAAAGGGCUGG 24 12246

SCNNlA-8398 + GCAGGUGGGGGGCAGUGG 18 12247

SCNNlA-8399 + GGCAGGUGGGGGGCAGUGG 19 12248

SCNNlA-6171 + AGGCAGGUGGGGGGCAGUGG 20 10020

SCNNlA-8400 + GAGGCAGGUGGGGGGCAGUGG 21 12249

SCNNlA-8401 + AGAGGCAGGUGGGGGGCAGUGG 22 12250

SCNNlA-8402 + UAGAGGCAGGUGGGGGGCAGUGG 23 12251

SCNNlA-8403 + GUAGAGGCAGGUGGGGGGCAGUGG 24

12252

SCNNlA-1630 + CAUGAUACCUCCCCUUGG 18 5479

SCNNlA-1631 + UCAUGAUACCUCCCCUUGG 19 5480

SCNNlA-1632 + CUCAUGAUACCUCCCCUUGG 20 5481

SCNNlA-1633 + GCUCAUGAUACCUCCCCUUGG 21 5482

SCNNlA-1634 + UGCUCAUGAUACCUCCCCUUGG 22 5483

SCNNlA-1635 + CUGCUCAUGAUACCUCCCCUUGG 23 5484

SCNNlA-1636 + ACUGCUCAUGAUACCUCCCCUUGG 24 5485

SCNNlA-8404 + UUCUUCAUUGUCCUAAUG 18 12253

SCNNlA-8405 + UUUCUUCAUUGUCCUAAUG 19 12254

SCNNlA-8406 + UUUUCUUCAUUGUCCUAAUG 20 12255

SCNNlA-8407 + UUUUUCUUCAUUGUCCUAAUG 21 12256

SCNNlA-8408 + AUUUUUCUUCAUUGUCCUAAUG 22 12257

SCNNlA-8409 + GAUUUUUCUUCAUUGUCCUAAUG 23 12258

SCNNlA-8410 + GGAUUUUUCUUCAUUGUCCUAAUG 24 12259

SCNNlA-8411 + GACAGAGAGAUAGGGAUG 18 12260

SCNNlA-8412 + GGACAGAGAGAUAGGGAUG 19 12261

SCNNlA-8413 + AGGACAGAGAGAUAGGGAUG 20 12262

SCNNlA-8414 + AAGGACAGAGAGAUAGGGAUG 21 12263

1416

5535.1 SCNNlA-8415 + GAAGGACAGAGAGAUAGGGAUG 22 12264

SCNNlA-8416 + CGAAGGACAGAGAGAUAGGGAUG 23 12265

SCNNlA-8417 + GCGAAGGACAGAGAGAUAGGGAUG 24 12266

SCNNlA-8418 + GAGCCUAGGGGCUCACUG 18 12267

SCNNlA-8419 + GGAGCCUAGGGGCUCACUG 19 12268

SCNNlA-8420 + GGGAGCCUAGGGGCUCACUG 20 12269

SCNNlA-8421 + GGGGAGCCUAGGGGCUCACUG 21 12270

SCNNlA-8422 + AGGGGAGCCUAGGGGCUCACUG 22 12271

SCNNlA-8423 + UAGGGGAGCCUAGGGGCUCACUG 23 12272

SCNNlA-8424 + CUAGGGGAGCCUAGGGGCUCACUG 24 12273

SCNNlA-8425 + GUCUCUGCCCCAGGACUG 18 12274

SCNNlA-8426 + UGUCUCUGCCCCAGGACUG 19 12275

SCNNlA-8427 + CUGUCUCUGCCCCAGGACUG 20 12276

SCNNlA-8428 + UCUGUCUCUGCCCCAGGACUG 21 12277

SCNNlA-8429 + UUCUGUCUCUGCCCCAGGACUG 22 12278

SCNNlA-8430 + AUUCUGUCUCUGCCCCAGGACUG 23 12279

SCNNlA-8431 + GAUUCUGUCUCUGCCCCAGGACUG 24 12280

SCNNlA-8432 + CUGGAGCCAGCAGACCUG 18 12281

SCNNlA-8433 + CCUGGAGCCAGCAGACCUG 19 12282

SCNNlA-5701 + UCCUGGAGCCAGCAGACCUG 20 9550

SCNNlA-8434 + UUCCUGGAGCCAGCAGACCUG 21 12283

SCNNlA-8435 + UUUCCUGGAGCCAGCAGACCUG 22 12284

SCNNlA-8436 + CUUUCCUGGAGCCAGCAGACCUG 23 12285

SCNNlA-8437 + CCUUUCCUGGAGCCAGCAGACCUG 24 12286

SCNNlA-8438 + CCUCACCCUCAGGCCCUG 18 12287

SCNNlA-8439 + GCCUCACCCUCAGGCCCUG 19 12288

SCNNlA-8440 + AGCCUCACCCUCAGGCCCUG 20 12289

SCNNlA-8441 + CAGCCUCACCCUCAGGCCCUG 21 12290

SCNNlA-8442 + UCAGCCUCACCCUCAGGCCCUG 22 12291

SCNNlA-8443 + GUCAGCCUCACCCUCAGGCCCUG 23 12292

SCNNlA-8444 + GGUCAGCCUCACCCUCAGGCCCUG 24 12293

SCNNlA-8445 + AGACAGGCAAGGAGGCUG 18 12294

SCNNlA-8446 + CAGACAGGCAAGGAGGCUG 19 12295

SCNNlA-5919 + GCAGACAGGCAAGGAGGCUG 20 9768

SCNNlA-8447 + CGCAGACAGGCAAGGAGGCUG 21 12296

SCNNlA-8448 + ACGCAGACAGGCAAGGAGGCUG 22 12297

SCNNlA-8449 + GACGCAGACAGGCAAGGAGGCUG 23 12298

SCNNlA-8450 + AGACGCAGACAGGCAAGGAGGCUG 24 12299

SCNNlA-8451 + CAGACCCAAAAAGGGCUG 18 12300

SCNNlA-8452 + UCAGACCCAAAAAGGGCUG 19 12301

SCNNlA-8453 + AUCAGACCCAAAAAGGGCUG 20 12302

SCNNlA-8454 + AAUCAGACCCAAAAAGGGCUG 21 12303

1417

5535.1 SCNNlA-8455 + GAAUCAGACCCAAAAAGGGCUG 22 12304

SCNNlA-8456 + AG A A U C AG ACC C A A A A AG G G C U G 23 12305

SCNNlA-8457 + GAGAAUCAGACCCAAAAAGGGCUG 24 12306

SCNNlA-8458 + GGGCGGGGGGAGGGGCUG 18 12307

SCNNlA-8459 + AGGGCGGGGGGAGGGGCUG 19 12308

SCNNlA-6176 + CAGGGCGGGGGGAGGGGCUG 20 10025

SCNNlA-8460 + GCAGGGCGGGGGGAGGGGCUG 21 12309

SCNNlA-8461 + AGCAGGGCGGGGGGAGGGGCUG 22 12310

SCNNlA-8462 + GAGCAGGGCGGGGGGAGGGGCUG 23 12311

SCNNlA-8463 + UGAGCAGGGCGGGGGGAGGGGCUG 24

12312

SCNNlA-1668 + GAGACCUGGUAUGGGCUG 18 5517

SCNNlA-1669 + UGAGACCUGGUAUGGGCUG 19 5518

SCNNlA-1670 + AUGAGACCUGGUAUGGGCUG 20 5519

SCNNlA-1671 + CAUGAGACCUGGUAUGGGCUG 21 5520

SCNNlA-1672 + CCAUGAGACCUGGUAUGGGCUG 22 5521

SCNNlA-1673 + UCCAUGAGACCUGGUAUGGGCUG 23 5522

SCNNlA-1674 + CUCCAUGAGACCUGGUAUGGGCUG 24 5523

SCNNlA-8464 + GGUGCAGCGGCCUGGCUG 18 12313

SCNNlA-8465 + AGGUGCAGCGGCCUGGCUG 19 12314

SCNNlA-5705 + CAGGUGCAGCGGCCUGGCUG 20 9554

SCNNlA-8466 + ACAGGUGCAGCGGCCUGGCUG 21 12315

SCNNlA-8467 + GACAGGUGCAGCGGCCUGGCUG 22 12316

SCNNlA-8468 + UGACAGGUGCAGCGGCCUGGCUG 23 12317

SCNNlA-8469 + CUGACAGGUGCAGCGGCCUGGCUG 24 12318

SCNNlA-8470 + GAGUUGGGGCCAAAAGUG 18 12319

SCNNlA-8471 + GGAGUUGGGGCCAAAAGUG 19 12320

SCNNlA-8472 + GGGAGUUGGGGCCAAAAGUG 20 12321

SCNNlA-8473 + CGGGAGUUGGGGCCAAAAGUG 21 12322

SCNNlA-8474 + GCGGGAGUUGGGGCCAAAAGUG 22 12323

SCNNlA-8475 + UGCGGGAGUUGGGGCCAAAAGUG 23 12324

SCNNlA-8476 + CUGCGGGAGUUGGGGCCAAAAGUG 24 12325

SCNNlA-8477 + GGAGUGGAGUGCCAAGUG 18 12326

SCNNlA-8478 + AGGAGUGGAGUGCCAAGUG 19 12327

SCNNlA-8479 + AAGGAGUGGAGUGCCAAGUG 20 12328

SCNNlA-8480 + UAAGGAGUGGAGUGCCAAGUG 21 12329

SCNNlA-8481 + AUAAGGAGUGGAGUGCCAAGUG 22 12330

SCNNlA-8482 + GAUAAGGAGUGGAGUGCCAAGUG 23 12331

SCNNlA-8483 + GGAUAAGGAGUGGAGUGCCAAGUG 24

12332

SCNNlA-8484 + GGCAGGUGGGGGGCAGUG 18 12333

SCNNlA-8485 + AGGCAGGUGGGGGGCAGUG 19 12334

1418

5535.1 SCNNlA-8486 + GAGGCAGGUGGGGGGCAGUG 20 12335

SCNNlA-8487 + AGAGGCAGGUGGGGGGCAGUG 21 12336

SCNNlA-8488 + UAGAGGCAGGUGGGGGGCAGUG 22 12337

SCNNlA-8489 + GUAGAGGCAGGUGGGGGGCAGUG 23 12338

SCNNlA-8490 + AGUAGAGGCAGGUGGGGGGCAGUG 24

12339

SCNNlA-8491 + AGGAGGCAGCCCAGAGUG 18 12340

SCNNlA-8492 + CAGGAGGCAGCCCAGAGUG 19 12341

SCNNlA-8493 + ACAGGAGGCAGCCCAGAGUG 20 12342

SCNNlA-8494 + CACAGGAGGCAGCCCAGAGUG 21 12343

SCNNlA-8495 + CCACAGGAGGCAGCCCAGAGUG 22 12344

SCNNlA-8496 + CCCA CAGGAGGCAGCCCAGAGUG 23 12345

SCNNlA-8497 + CCCCACAGGAGGCAGCCCAGAGUG 24 12346

SCNNlA-8498 + AAG C AGG CAC U G AAG G U G 18 12347

SCNNlA-8499 + A A AG CAGGCACUGAAGGUG 19 12348

SCNNlA-8500 + GAAAGCAGGCACUGAAGGUG 20 12349

SCNNlA-8501 + GGAAAGCAGGCACUGAAGGUG 21 12350

SCNNlA-8502 + GGGAAAGCAGGCACUGAAGGUG 22 12351

SCNNlA-8503 + AGGGAAAGCAGGCACUGAAGGUG 23 12352

SCNNlA-8504 + C AGG G AAAG CAG G C ACU G AAG G U G 24 12353

SCNNlA-8505 + AGUGAGUAGAGGCAGGUG 18 12354

SCNNlA-8506 + GAGUGAGUAGAGGCAGGUG 19 12355

SCNNlA-5713 + UGAGUGAGUAGAGGCAGGUG 20 9562

SCNNlA-8507 + CUGAGUGAGUAGAGGCAGGUG 21 12356

SCNNlA-8508 + ACUGAGUGAGUAGAGGCAGGUG 22 12357

SCNNlA-8509 + CACUGAGUGAGUAGAGGCAGGUG 23 12358

SCNNlA-8510 + GCACUGAGUGAGUAGAGGCAGGUG 24 12359

SCNNlA-8511 + GGGACAGGAUGGCAGGUG 18 12360

SCNNlA-8512 + GGGGACAGGAUGGCAGGUG 19 12361

SCNNlA-5920 + GGGGGACAGGAUGGCAGGUG 20 9769

SCNNlA-8513 + UGGGGGACAGGAUGGCAGGUG 21 12362

SCNNlA-8514 + CUGGGGGACAGGAUGGCAGGUG 22 12363

SCNNlA-8515 + GCUGGGGGACAGGAUGGCAGGUG 23 12364

SCNNlA-8516 + GGCUGGGGGACAGGAUGGCAGGUG 24

12365

SCNNlA-8517 + GCUGAGAGGGCCUGGGUG 18 12366

SCNNlA-8518 + GGCUGAGAGGGCCUGGGUG 19 12367

SCNNlA-6177 + AGGCUGAGAGGGCCUGGGUG 20 10026

SCNNlA-8519 + CAGGCUGAGAGGGCCUGGGUG 21 12368

SCNNlA-8520 + CCAGGCUGAGAGGGCCUGGGUG 22 12369

SCNNlA-8521 + GCCAGGCUGAGAGGGCCUGGGUG 23 12370

SCNNlA-8522 + AGCCAGGCUGAGAGGGCCUGGGUG 24 12371

1419

5535.1 SCNNlA-1699 + GAGCCCCGGAGUGGAUUG 18 5548

SCNNlA-1700 + UGAGCCCCGGAGUGGAUUG 19 5549

SCNNlA-419 + AUGAGCCCCGGAGUGGAUUG 20 4268

SCNNlA-1701 + CAUGAGCCCCGGAGUGGAUUG 21 5550

SCNNlA-1702 + UCAUGAGCCCCGGAGUGGAUUG 22 5551

SCNNlA-1703 + UUCAUGAGCCCCGGAGUGGAUUG 23 5552

SCNNlA-1704 + CUUCAUGAGCCCCGGAGUGGAUUG 24 5553

SCNNlA-8523 + GCUGUGGUCACAGAGUUG 18 12372

SCNNlA-8524 + UGCUGUGGUCACAGAGUUG 19 12373

SCNNlA-8525 + CUGCUGUGGUCACAGAGUUG 20 12374

SCNNlA-8526 + CCUGCUGUGGUCACAGAGUUG 21 12375

SCNNlA-8527 + CCCUGCUGUGGUCACAGAGUUG 22 12376

SCNNlA-8528 + CCCCUGCUGUGGUCACAGAGUUG 23 12377

SCNNlA-8529 + GCCCCUGCUGUGGUCACAGAGUUG 24 12378

SCNNlA-8530 + AGGAGGAGAAAUUCGUUG 18 12379

SCNNlA-8531 + GAGGAGGAGAAAUUCGUUG 19 12380

SCNNlA-8532 + GGAGGAGGAGAAAUUCGUUG 20 12381

SCNNlA-8533 + GGGAGGAGGAGAAAUUCGUUG 21 12382

SCNNlA-8534 + UGGGAGGAGGAGAAAUUCGUUG 22 12383

SCNNlA-8535 + CUGGGAGGAGGAGAAAUUCGUUG 23 12384

SCNNlA-8536 + CCUGGGAGGAGGAGAAAUUCGUUG 24 12385

SCNNlA-8537 + GAGGUUAGAAAACAAAAU 18 12386

SCNNlA-8538 + UGAGGUUAGAAAACAAAAU 19 12387

SCNNlA-5720 + CUG AGG U U AG AAAACAAAAU 20 9569

SCNNlA-8539 + UCUGAGGUUAGAAAACAAAAU 21 12388

SCNNlA-8540 + UUCUGAGGUUAGAAAACAAAAU 22 12389

SCNNlA-8541 + UUUCUGAGGUUAG A A A AC A A A A U 23 12390

SCNNlA-8542 + UUUUCUGAGGU U AG AAAAC AAAAU 24 12391

SCNNlA-8543 + U C ACAG AG U U G CAG G AA U 18 12392

SCNNlA-8544 + GUCACAGAGUUGCAGGAAU 19 12393

SCNNlA-8545 + GGUCACAGAGUUGCAGGAAU 20 12394

SCNNlA-8546 + UGGUCACAGAGUUGCAGGAAU 21 12395

SCNNlA-8547 + GUGGUCACAGAGUUGCAGGAAU 22 12396

SCNNlA-8548 + UGUGGUCACAGAGUUGCAGGAAU 23 12397

SCNNlA-8549 + CUGUGGUCACAGAGUUGCAGGAAU 24 12398

SCNNlA-8550 + UUCUCAGAGAUAAGACAU 18 12399

SCNNlA-8551 + UUUCUCAGAGAUAAGACAU 19 12400

SCNNlA-8552 + AUUUCUCAGAGAUAAGACAU 20 12401

SCNNlA-8553 + GAUUUCUCAGAGAUAAGACAU 21 12402

SCNNlA-8554 + AGAUUUCUCAGAGAUAAGACAU 22 12403

SCNNlA-8555 + CAGAUUUCUCAGAGAUAAGACAU 23 12404

SCNNlA-8556 + UCAGAUUUCUCAGAGAUAAGACAU 24 12405

1420

5535.1 SCNNlA-8557 + UUCCUGAGACAGACUCAU 18 12406

SCNNlA-8558 + CUUCCUGAGACAGACUCAU 19 12407

SCNNlA-6179 + ACUUCCUGAGACAGACUCAU 20 10028

SCNNlA-8559 + UACUUCCUGAGACAGACUCAU 21 12408

SCNNlA-8560 + UUACUUCCUGAGACAGACUCAU 22 12409

SCNNlA-8561 + UUUACUUCCUGAGACAGACUCAU 23 12410

SCNNlA-8562 + AUUUACUUCCUGAGACAGACUCAU 24 12411

SCNNlA-8563 + CAGGUGAGGGGCAAAGAU 18 12412

SCNNlA-8564 + GCAGGUGAGGGGCAAAGAU 19 12413

SCNNlA-8565 + GGCAGGUGAGGGGCAAAGAU 20 12414

SCNNlA-8566 + UGGCAGGUGAGGGGCAAAGAU 21 12415

SCNNlA-8567 + AUGGCAGGUGAGGGGCAAAGAU 22 12416

SCNNlA-8568 + GAUGGCAGGUGAGGGGCAAAGAU 23 12417

SCNNlA-8569 + GGAUGGCAGGUGAGGGGCAAAGAU 24

12418

SCNNlA-8570 + UUAAUGCAG C A A A AG G A U 18 12419

SCNNlA-8571 + CUUAAUGCAGCAAAAGGAU 19 12420

SCNNlA-8572 + ACUUAAUGCAG C A A A AG G A U 20 12421

SCNNlA-8573 + AACUUAAUGCAG C A A A AG G A U 21 12422

SCNNlA-8574 + AAACUUAAUGCAGCAAAAGGAU 22 12423

SCNNlA-8575 + C A A AC U U A A U G C AG C A A A AG G A U 23 12424

SCNNlA-8576 + C C A A AC U U A A U G C AG C A A A AG G A U 24 12425

SCNNlA-8577 + GACAGACUCAUGGGGGAU 18 12426

SCNNlA-8578 + AGACAGACUCAUGGGGGAU 19 12427

SCNNlA-5272 + GAGACAGACUCAUGGGGGAU 20 9121

SCNNlA-8579 + UGAGACAGACUCAUGGGGGAU 21 12428

SCNNlA-8580 + CUGAGACAGACUCAUGGGGGAU 22 12429

SCNNlA-8581 + CCUGAGACAGACUCAUGGGGGAU 23 12430

SCNNlA-8582 + UCCUGAGACAGACUCAUGGGGGAU 24 12431

SCNNlA-8583 + GCUCAGGUGCACCUGGAU 18 12432

SCNNlA-8584 + GGCUCAGGUGCACCUGGAU 19 12433

SCNNlA-8585 + GGGCUCAGGUGCACCUGGAU 20 12434

SCNNlA-8586 + GGGGCUCAGGUGCACCUGGAU 21 12435

SCNNlA-8587 + CGGGGCUCAGGUGCACCUGGAU 22 12436

SCNNlA-8588 + UCGGGGCUCAGGUGCACCUGGAU 23 12437

SCNNlA-8589 + AUCGGGGCUCAGGUGCACCUGGAU 24 12438

SCNNlA-1717 + AUGAGCCCCGGAGUGGAU 18 5566

SCNNlA-1718 + CAUGAGCCCCGGAGUGGAU 19 5567

SCNNlA-420 + UCAUGAGCCCCGGAGUGGAU 20 4269

SCNNlA-1719 + UUCAUGAGCCCCGGAGUGGAU 21 5568

SCNNlA-1720 + CUUCAUGAGCCCCGGAGUGGAU 22 5569

SCNNlA-1721 + CCUUCAUGAGCCCCGGAGUGGAU 23 5570

1421

5535.1 SCNNlA-1722 + CCCUUCAUGAGCCCCGGAGUGGAU 24 5571

SCNNlA-8590 + AGGGCCACGCAGGACACU 18 12439

SCNNlA-8591 + GAGGGCCACGCAGGACACU 19 12440

SCNNlA-8592 + CGAGGGCCACGCAGGACACU 20 12441

SCNNlA-8593 + GCGAGGGCCACGCAGGACACU 21 12442

SCNNlA-8594 + CGCGAGGGCCACGCAGGACACU 22 12443

SCNNlA-8595 + GCGCGAGGGCCACGCAGGACACU 23 12444

SCNNlA-8596 + AGCGCGAGGGCCACGCAGGACACU 24 12445

SCNNlA-8597 + GGCUCACUGCAGGAGACU 18 12446

SCNNlA-8598 + GGGCUCACUGCAGGAGACU 19 12447

SCNNlA-8599 + GGGGCUCACUGCAGGAGACU 20 12448

SCNNlA-8600 + AGGGGCUCACUGCAGGAGACU 21 12449

SCNNlA-8601 + UAGGGGCUCACUGCAGGAGACU 22 12450

SCNNlA-8602 + CUAGGGGCUCACUGCAGGAGACU 23 12451

SCNNlA-8603 + CCUAGGGGCUCACUGCAGGAGACU 24 12452

SCNNlA-8604 + AAAGGGCUGGAGGAGACU 18 12453

SCNNlA-8605 + AAAAGGGCUGGAGGAGACU 19 12454

SCNNlA-5729 + AAAAAGGGCUGGAGGAGACU 20 9578

SCNNlA-8606 + CAAAAAGGGCUGGAGGAGACU 21 12455

SCNNlA-8607 + CCAAAAAGGGCUGGAGGAGACU 22 12456

SCNNlA-8608 + CCCAAAAAGGGCUGGAGGAGACU 23 12457

SCNNlA-8609 + ACCCAAAAAGGGCUGGAGGAGACU 24 12458

SCNNlA-8610 + GACCUGAGAAGGCGGACU 18 12459

SCNNlA-8611 + GGACCUGAGAAGGCGGACU 19 12460

SCNNlA-8612 + UGGACCUGAGAAGGCGGACU 20 12461

SCNNlA-8613 + CUGGACCUGAGAAGGCGGACU 21 12462

SCNNlA-8614 + ACUGGACCUGAGAAGGCGGACU 22 12463

SCNNlA-8615 + UACUGGACCUGAGAAGGCGGACU 23 12464

SCNNlA-8616 + GUACUGGACCUGAGAAGGCGGACU 24 12465

SCNNlA-8617 + CCUGGAGCCAGCAGACCU 18 12466

SCNNlA-8618 + UCCUGGAGCCAGCAGACCU 19 12467

SCNNlA-8619 + UUCCUGGAGCCAGCAGACCU 20 12468

SCNNlA-8620 + UUUCCUGGAGCCAGCAGACCU 21 12469

SCNNlA-8621 + CUUUCCUGGAGCCAGCAGACCU 22 12470

SCNNlA-8622 + CCUUUCCUGGAGCCAGCAGACCU 23 12471

SCNNlA-8623 + ACCUUUCCUGGAGCCAGCAGACCU 24 12472

SCNNlA-8624 + ACUGGGAGUACUGGACCU 18 12473

SCNNlA-8625 + AACUGGGAGUACUGGACCU 19 12474

SCNNlA-8626 + GAACUGGGAGUACUGGACCU 20 12475

SCNNlA-8627 + UGAACUGGGAGUACUGGACCU 21 12476

SCNNlA-8628 + GUGAACUGGGAGUACUGGACCU 22 12477

SCNNlA-8629 + GGUGAACUGGGAGUACUGGACCU 23 12478

1422

5535.1 SCNNlA-8630 + AGGUGAACUGGGAGUACUGGACCU 24 12479

SCNNlA-1735 + GCUCAUGAUACCUCCCCU 18 5584

SCNNlA-1736 + UGCUCAUGAUACCUCCCCU 19 5585

SCNNlA-457 + CUGCUCAUGAUACCUCCCCU 20 4306

SCNNlA-1737 + ACUGCUCAUGAUACCUCCCCU 21 5586

SCNNlA-1738 + UACUGCUCAUGAUACCUCCCCU 22 5587

SCNNlA-1739 + AUACUGCUCAUGAUACCUCCCCU 23 5588

SCNNlA-1740 + GAUACUGCUCAUGAUACCUCCCCU 24 5589

SCNNlA-8631 + CACGCCUAGACAGGCCCU 18 12480

SCNNlA-8632 + ACACGCCUAGACAGGCCCU 19 12481

SCNNlA-5734 + CACACGCCUAGACAGGCCCU 20 9583

SCNNlA-8633 + GCACACGCCUAGACAGGCCCU 21 12482

SCNNlA-8634 + GGCACACGCCUAGACAGGCCCU 22 12483

SCNNlA-8635 + UGGCACACGCCUAGACAGGCCCU 23 12484

SCNNlA-8636 + AUGGCACACGCCUAGACAGGCCCU 24 12485

SCNNlA-8637 + CAAGGGCUAGGGGAGCCU 18 12486

SCNNlA-8638 + CCAAGGGCUAGGGGAGCCU 19 12487

SCNNlA-5275 + GCCAAGGGCUAGGGGAGCCU 20 9124

SCNNlA-8639 + AGCCAAGGGCUAGGGGAGCCU 21 12488

SCNNlA-8640 + GAGCCAAGGGCUAGGGGAGCCU 22 12489

SCNNlA-8641 + AGAGCCAAGGGCUAGGGGAGCCU 23 12490

SCNNlA-8642 + AAGAGCCAAGGGCUAGGGGAGCCU 24 12491

SCNNlA-8643 + CAGAAUUCUCCUCCUCCU 18 12492

SCNNlA-8644 + UCAGAAUUCUCCUCCUCCU 19 12493

SCNNlA-8645 + UUCAGAAUUCUCCUCCUCCU 20 12494

SCNNlA-8646 + AUUCAGAAUUCUCCUCCUCCU 21 12495

SCNNlA-8647 + AAUUCAGAAUUCUCCUCCUCCU 22 12496

SCNNlA-8648 + GAAUUCAGAAUUCUCCUCCUCCU 23 12497

SCNNlA-8649 + AGAAUUCAGAAUUCUCCUCCUCCU 24 12498

SCNNlA-8650 + AGGGGCCCAGGUGAAGCU 18 12499

SCNNlA-8651 + GAGGGGCCCAGGUGAAGCU 19 12500

SCNNlA-5923 + GGAGGGGCCCAGGUGAAGCU 20 9772

SCNNlA-8652 + GGGAGGGGCCCAGGUGAAGCU 21 12501

SCNNlA-8653 + CGGGAGGGGCCCAGGUGAAGCU 22 12502

SCNNlA-8654 + CCGGGAGGGGCCCAGGUGAAGCU 23 12503

SCNNlA-8655 + CCCGGGAGGGGCCCAGGUGAAGCU 24 12504

SCNNlA-8656 + GAUCCUGAGCCCACAGCU 18 12505

SCNNlA-8657 + GGAUCCUGAGCCCACAGCU 19 12506

SCNNlA-5740 + AGGAUCCUGAGCCCACAGCU 20 9589

SCNNlA-8658 + AAGGAUCCUGAGCCCACAGCU 21 12507

SCNNlA-8659 + GAAGGAUCCUGAGCCCACAGCU 22 12508

SCNNlA-8660 + AGAAGGAUCCUGAGCCCACAGCU 23 12509

1423

5535.1 SCNNlA-8661 + UAGAAGGAUCCUGAGCCCACAGCU 24 12510

SCNNlA-1741 + CAGGGUCAAGGCUGAGCU 18 5590

SCNNlA-1742 + UCAGGGUCAAGGCUGAGCU 19 5591

SCNNlA-1743 + GUCAGGGUCAAGGCUGAGCU 20 5592

SCNNlA-1744 + GGUCAGGGUCAAGGCUGAGCU 21 5593

SCNNlA-1745 + GGGUCAGGGUCAAGGCUGAGCU 22 5594

SCNNlA-1746 + AGGGUCAGGGUCAAGGCUGAGCU 23 5595

SCNNlA-1747 + AAGGGUCAGGGUCAAGGCUGAGCU 24 5596

SCNNlA-8662 + GAAGGGGCCAGCCAGGCU 18 12511

SCNNlA-8663 + AGAAGGGGCCAGCCAGGCU 19 12512

SCNNlA-8664 + GAGAAGGGGCCAGCCAGGCU 20 12513

SCNNlA-8665 + GGAGAAGGGGCCAGCCAGGCU 21 12514

SCNNlA-8666 + AGGAGAAGGGGCCAGCCAGGCU 22 12515

SCNNlA-8667 + AAGGAGAAGGGGCCAGCCAGGCU 23 12516

SCNNlA-8668 + CAAGGAGAAGGGGCCAGCCAGGCU 24 12517

SCNNlA-8669 + CAGACAGGCAAGGAGGCU 18 12518

SCNNlA-8670 + GCAGACAGGCAAGGAGGCU 19 12519

SCNNlA-5742 + CGCAGACAGGCAAGGAGGCU 20 9591

SCNNlA-8671 + ACGCAGACAGGCAAGGAGGCU 21 12520

SCNNlA-8672 + GACGCAGACAGGCAAGGAGGCU 22 12521

SCNNlA-8673 + AGACGCAGACAGGCAAGGAGGCU 23 12522

SCNNlA-8674 + UAGACGCAGACAGGCAAGGAGGCU 24 12523

SCNNlA-8675 + ACAUAAGAGCCAAGGGCU 18 12524

SCNNlA-8676 + GACAUAAGAGCCAAGGGCU 19 12525

SCNNlA-5743 + AGACAUAAGAGCCAAGGGCU 20 9592

SCNNlA-8677 + AAGACAUAAGAGCCAAGGGCU 21 12526

SCNNlA-8678 + UAAGACAUAAGAGCCAAGGGCU 22 12527

SCNNlA-8679 + AUAAGACAUAAGAGCCAAGGGCU 23 12528

SCNNlA-8680 + GAUAAGACAUAAGAGCCAAGGGCU 24 12529

SCNNlA-8681 + AGGGCGGGGGGAGGGGCU 18 12530

SCNNlA-8682 + CAGGGCGGGGGGAGGGGCU 19 12531

SCNNlA-8683 + GCAGGGCGGGGGGAGGGGCU 20 12532

SCNNlA-8684 + AGCAGGGCGGGGGGAGGGGCU 21 12533

SCNNlA-8685 + GAGCAGGGCGGGGGGAGGGGCU 22 12534

SCNNlA-8686 + UGAGCAGGGCGGGGGGAGGGGCU 23 12535

SCNNlA-8687 + GUGAGCAGGGCGGGGGGAGGGGCU 24

12536

SCNNlA-8688 + AGGUGCAGCGGCCUGGCU 18 12537

SCNNlA-8689 + CAGGUGCAGCGGCCUGGCU 19 12538

SCNNlA-5744 + ACAGGUGCAGCGGCCUGGCU 20 9593

SCNNlA-8690 + GACAGGUGCAGCGGCCUGGCU 21 12539

SCNNlA-8691 + UGACAGGUGCAGCGGCCUGGCU 22 12540

1424

5535.1 SCNNlA-8692 + CUGACAGGUGCAGCGGCCUGGCU 23 12541

SCNNlA-8693 + CCUGACAGGUGCAGCGGCCUGGCU 24 12542

SCNNlA-8694 + UUUCAUAUCAAGGGCUCU 18 12543

SCNNlA-8695 + UUUUCAUAUCAAGGGCUCU 19 12544

SCNNlA-8696 + GUUUUCAUAUCAAGGGCUCU 20 12545

SCNNlA-8697 + AGUUUUCAUAUCAAGGGCUCU 21 12546

SCNNlA-8698 + UAGUUUUCAUAUCAAGGGCUCU 22 12547

SCNNlA-8699 + AUAGUUUUCAUAUCAAGGGCUCU 23 12548

SCNNlA-8700 + AAUAGUUUUCAUAUCAAGGGCUCU 24 12549

SCNNlA-8701 + GGUUAUCUCCUUGGCUCU 18 12550

SCNNlA-8702 + GGGUUAUCUCCUUGGCUCU 19 12551

SCNNlA-8703 + UGGGUUAUCUCCUUGGCUCU 20 12552

SCNNlA-8704 + CUGGGUUAUCUCCUUGGCUCU 21 12553

SCNNlA-8705 + GCUGGGUUAUCUCCUUGGCUCU 22 12554

SCNNlA-8706 + UGCUGGGUUAUCUCCUUGGCUCU 23 12555

SCNNlA-8707 + GUGCUGGGUUAUCUCCUUGGCUCU 24 12556

SCNNlA-8708 + UGCAGAUCUCAGAUUUCU 18 12557

SCNNlA-8709 + GUGCAGAUCUCAGAUUUCU 19 12558

SCNNlA-8710 + AGUGCAGAUCUCAGAUUUCU 20 12559

SCNNlA-8711 + AAGUGCAGAUCUCAGAUUUCU 21 12560

SCNNlA-8712 + AAAGUGCAGAUCUCAGAUUUCU 22 12561

SCNNlA-8713 + AAAAGUGCAGAUCUCAGAUUUCU 23 12562

SCNNlA-8714 + CAAAAGUGCAGAUCUCAGAUUUCU 24 12563

SCNNlA-8715 + CCUCCCCGCUCACUAAGU 18 12564

SCNNlA-8716 + UCCUCCCCGCUCACUAAGU 19 12565

SCNNlA-5752 + CUCCUCCCCGCUCACUAAGU 20 9601

SCNNlA-8717 + UCUCCUCCCCGCUCACUAAGU 21 12566

SCNNlA-8718 + GUCUCCUCCCCGCUCACUAAGU 22 12567

SCNNlA-8719 + GGUCUCCUCCCCGCUCACUAAGU 23 12568

SCNNlA-8720 + AGGUCUCCUCCCCGCUCACUAAGU 24 12569

SCNNlA-8721 + GAGGGGCUGAGGAGGAGU 18 12570

SCNNlA-8722 + GGAGGGGCUGAGGAGGAGU 19 12571

SCNNlA-8723 + GGGAGGGGCUGAGGAGGAGU 20 12572

SCNNlA-8724 + GGGGAGGGGCUGAGGAGGAGU 21 12573

SCNNlA-8725 + GGGGGAGGGGCUGAGGAGGAGU 22 12574

SCNNlA-8726 + GGGGGGAGGGGCUGAGGAGGAGU 23 12575

SCNNlA-8727 + CGGGGGGAGGGGCUGAGGAGGAGU 24

12576

SCNNlA-8728 + CAGCAGACCUGCGGGAGU 18 12577

SCNNlA-8729 + CCAGCAGACCUGCGGGAGU 19 12578

SCNNlA-5278 + GCCAGCAGACCUGCGGGAGU 20 9127

SCNNlA-8730 + AGCCAGCAGACCUGCGGGAGU 21 12579

1425

5535.1 SCNNlA-8731 + GAGCCAGCAGACCUGCGGGAGU 22 12580

SCNNlA-8732 + GGAGCCAGCAGACCUGCGGGAGU 23 12581

SCNNlA-8733 + UGGAGCCAGCAGACCUGCGGGAGU 24 12582

SCNNlA-8734 + GAGUGAGUAGAGGCAGGU 18 12583

SCNNlA-8735 + UGAGUGAGUAGAGGCAGGU 19 12584

SCNNlA-5756 + CUGAGUGAGUAGAGGCAGGU 20 9605

SCNNlA-8736 + ACUGAGUGAGUAGAGGCAGGU 21 12585

SCNNlA-8737 + CACUGAGUGAGUAGAGGCAGGU 22 12586

SCNNlA-8738 + GCACUGAGUGAGUAGAGGCAGGU 23 12587

SCNNlA-8739 + GGCACUGAGUGAGUAGAGGCAGGU 24 12588

SCNNlA-8740 + GGGGACAGGAUGGCAGGU 18 12589

SCNNlA-8741 + GGGGGACAGGAUGGCAGGU 19 12590

SCNNlA-8742 + UGGGGGACAGGAUGGCAGGU 20 12591

SCNNlA-8743 + CUGGGGGACAGGAUGGCAGGU 21 12592

SCNNlA-8744 + GCUGGGGGACAGGAUGGCAGGU 22 12593

SCNNlA-8745 + GGCUGGGGGACAGGAUGGCAGGU 23 12594

SCNNlA-8746 + AGGCUGGGGGACAGGAUGGCAGGU 24

12595

SCNNlA-8747 + UGCAGGGCUCCAGGAGGU 18 12596

SCNNlA-8748 + CUGCAGGGCUCCAGGAGGU 19 12597

SCNNlA-8749 + ACUGCAGGGCUCCAGGAGGU 20 12598

SCNNlA-8750 + GACUGCAGGGCUCCAGGAGGU 21 12599

SCNNlA-8751 + GGACUGCAGGGCUCCAGGAGGU 22 12600

SCNNlA-8752 + AGGACUGCAGGGCUCCAGGAGGU 23 12601

SCNNlA-8753 + CAGGACUGCAGGGCUCCAGGAGGU 24 12602

SCNNlA-8754 + AAAUCAGUUUUCUGAGGU 18 12603

SCNNlA-8755 + UAAAUCAGUUUUCUGAGGU 19 12604

SCNNlA-8756 + AUAAAUCAGUUUUCUGAGGU 20 12605

SCNNlA-8757 + GAUAAAUCAGUUUUCUGAGGU 21 12606

SCNNlA-8758 + GGAUAAAUCAGUUUUCUGAGGU 22 12607

SCNNlA-8759 + AGGAUAAAUCAGUUUUCUGAGGU 23 12608

SCNNlA-8760 + AAGGAUAAAUCAGUUUUCUGAGGU 24 12609

SCNNlA-8761 + AAGGAGAGAGAGGAGGGU 18 12610

SCNNlA-8762 + CAAGGAGAGAGAGGAGGGU 19 12611

SCNNlA-8763 + GCAAGGAGAGAGAGGAGGGU 20 12612

SCNNlA-8764 + AGCAAGGAGAGAGAGGAGGGU 21 12613

SCNNlA-8765 + GAGCAAGGAGAGAGAGGAGGGU 22 12614

SCNNlA-8766 + UGAGCAAGGAGAGAGAGGAGGGU 23 12615

SCNNlA-8767 + GUGAGCAAGGAGAGAGAGGAGGGU 24

12616

SCNNlA-8768 + GGCUGAGAGGGCCUGGGU 18 12617

SCNNlA-8769 + AGGCUGAGAGGGCCUGGGU 19 12618

1426

5535.1 SCNNlA-6188 + CAGGCUGAGAGGGCCUGGGU 20 10037

SCNNlA-8770 + CCAGGCUGAGAGGGCCUGGGU 21 12619

SCNNlA-8771 + GCCAGGCUGAGAGGGCCUGGGU 22 12620

SCNNlA-8772 + AGCCAGGCUGAGAGGGCCUGGGU 23 12621

SCNNlA-8773 + CAGCCAGGCUGAGAGGGCCUGGGU 24 12622

SCNNlA-1772 + CCCUCCAUGAGACCUGGU 18 5621

SCNNlA-1773 + CCCCUCCAUGAGACCUGGU 19 5622

SCNNlA-199 + UCCCCUCCAUGAGACCUGGU 20 828

SCNNlA-1774 + UUCCCCUCCAUGAGACCUGGU 21 5623

SCNNlA-1775 + GUUCCCCUCCAUGAGACCUGGU 22 5624

SCNNlA-1776 + UGUUCCCCUCCAUGAGACCUGGU 23 5625

SCNNlA-1777 + UUGUUCCCCUCCAUGAGACCUGGU 24 5626

SCNNlA-8774 + CAGGUGGGGGGCAGUGGU 18 12623

SCNNlA-8775 + GCAGGUGGGGGGCAGUGGU 19 12624

SCNNlA-5928 + GGCAGGUGGGGGGCAGUGGU 20 9777

SCNNlA-8776 + AGGCAGGUGGGGGGCAGUGGU 21 12625

SCNNlA-8777 + GAGGCAGGUGGGGGGCAGUGGU 22 12626

SCNNlA-8778 + AGAGGCAGGUGGGGGGCAGUGGU 23 12627

SCNNlA-8779 + UAGAGGCAGGUGGGGGGCAGUGGU 24

12628

SCNNlA-8780 + UCAUAUCAAGGGCUCUGU 18 12629

SCNNlA-8781 + UUCAUAUCAAGGGCUCUGU 19 12630

SCNNlA-8782 + UUUCAUAUCAAGGGCUCUGU 20 12631

SCNNlA-8783 + UUUUCAUAUCAAGGGCUCUGU 21 12632

SCNNlA-8784 + GUUUUCAUAUCAAGGGCUCUGU 22 12633

SCNNlA-8785 + AGUUUUCAUAUCAAGGGCUCUGU 23 12634

SCNNlA-8786 + UAGUUUUCAUAUCAAGGGCUCUGU 24 12635

SCNNlA-1778 + UGAGCCCCGGAGUGGAUU 18 5627

SCNNlA-1779 + AUGAGCCCCGGAGUGGAUU 19 5628

SCNNlA-425 + CAUGAGCCCCGGAGUGGAUU 20 4274

SCNNlA-1780 + UCAUGAGCCCCGGAGUGGAUU 21 5629

SCNNlA-1781 + UUCAUGAGCCCCGGAGUGGAUU 22 5630

SCNNlA-1782 + CUUCAUGAGCCCCGGAGUGGAUU 23 5631

SCNNlA-1783 + CCUUCAUGAGCCCCGGAGUGGAUU 24 5632

SCNNlA-8787 + UGUUUGAUCUCAAAGGUU 18 12636

SCNNlA-8788 + CUGUUUGAUCUCAAAGGUU 19 12637

SCNNlA-8789 + GCUGUUUGAUCUCAAAGGUU 20 12638

SCNNlA-8790 + GGCUGUUUGAUCUCAAAGGUU 21 12639

SCNNlA-8791 + UGGCUGUUUGAUCUCAAAGGUU 22 12640

SCNNlA-8792 + CUGGCUGUUUGAUCUCAAAGGUU 23 12641

SCNNlA-8793 + CCUGGCUGUUUGAUCUCAAAGGUU 24 12642

SCNNlA-8794 + C A AG G A U AAA UCAGUUUU 18 12643

1427

5535.1 SCNNlA-8795 + C C A AG G A U AAA UCAGUUUU 19 12644

SCNNlA-8796 + CCCAAGG AU AAAU CAG U U U U 20 12645

SCNNlA-8797 + UCCCAAGGAUAAAUCAGUUUU 21 12646

SCNNlA-8798 + UUCCCAAGGAUAAAUCAGUUUU 22 12647

SCNNlA-8799 + CUUCCCAAGGAUAAAUCAGUUUU 23 12648

SCNNlA-8800 + CCU U CCCAAGG AU AAAU CAG U U U U 24 12649

SCNNlA-8801 + GUCAGAGCCGGGAGUUUU 18 12650

SCNNlA-8802 + AG U CAG AG CCGGGAGUUUU 19 12651

SCNNlA-8803 + GAGUCAGAGCCGGGAGUUUU 20 12652

SCNNlA-8804 + GGAGUCAGAGCCGGGAGUUUU 21 12653

SCNNlA-8805 + AGGAGUCAGAGCCGGGAGUUUU 22 12654

SCNNlA-8806 + GAGGAGUCAGAGCCGGGAGUUUU 23 12655

SCNNlA-8807 + GGAGGAGUCAGAGCCGGGAGUUUU 24

12656

SCNNlA-8808 - G C AG C C A AC AG U G U A A A A 18 12657

SCNNlA-8809 - G G C AG C C A AC AG U G U A A A A 19 12658

SCNNlA-8810 - UGGCAGCCAACAGUGUAAAA 20 12659

SCNNlA-8811 - CUGGCAGCCAACAGUGU A A A A 21 12660

SCNNlA-8812 - CCUGGCAGCCAACAGUGUAAAA 22 12661

SCNNlA-8813 - GCCUGGCAGCCAACAGUGU A A A A 23 12662

SCNNlA-8814 - GGCCUGGCAGC C A AC AG U G U A A A A 24 12663

SCNNlA-8815 - UCUUUUAAAGUGUACAAA 18 12664

SCNNlA-8816 - AUCUUUUAAAGUGUACAAA 19 12665

SCNNlA-8817 - AAUCUUUUAAAGUGUACAAA 20 12666

SCNNlA-8818 - CAAUCUUUUAAAGUGUACAAA 21 12667

SCNNlA-8819 - ACAAUCUUUUAAAGUGUACAAA 22 12668

SCNNlA-8820 - GACAAUCU U U U AAAG UG U ACAAA 23 12669

SCNNlA-8821 - AGACAAUCUUUUAAAGUGUACAAA 24 12670

SCNNlA-8822 - GAGCAGGAGAGACCCAAA 18 12671

SCNNlA-8823 - AGAGCAGGAGAGACCCAAA 19 12672

SCNNlA-8824 - GAGAGCAGGAGAGACCCAAA 20 12673

SCNNlA-8825 - GGAGAGCAGGAGAGACCCAAA 21 12674

SCNNlA-8826 - AGGAGAGCAGGAGAGACCCAAA 22 12675

SCNNlA-8827 - GAGGAGAGCAGGAGAGACCCAAA 23 12676

SCNNlA-8828 - AGAGGAGAGCAGGAGAGACCCAAA 24 12677

SCNNlA-8829 - CAGGCAUGAGCUGGCAAA 18 12678

SCNNlA-8830 - UCAGGCAUGAGCUGGCAAA 19 12679

SCNNlA-8831 - UUCAGGCAUGAGCUGGCAAA 20 12680

SCNNlA-8832 - UUUCAGGCAUGAGCUGGCAAA 21 12681

SCNNlA-8833 - AUUUCAGGCAUGAGCUGGCAAA 22 12682

SCNNlA-8834 - GAUUUCAGGCAUGAGCUGGCAAA 23 12683

SCNNlA-8835 - GGAUUUCAGGCAUGAGCUGGCAAA 24 12684

1428

5535.1 SCNNlA-8836 - AGGGGGCAGAGACAGAAA 18 12685

SCNNlA-8837 - AAGGGGGCAGAGACAGAAA 19 12686

SCNNlA-5863 - GAAGGGGGCAGAGACAGAAA 20 9712

SCNNlA-8838 - GGAAGGGGGCAGAGACAGAAA 21 12687

SCNNlA-8839 - AGGAAGGGGGCAGAGACAGAAA 22 12688

SCNNlA-8840 - AAGGAAGGGGGCAGAGACAGAAA 23 12689

SCNNlA-8841 - AAAGGAAGGGGGCAGAGACAGAAA 24 12690

SCNNlA-8842 - GAGGAGGCAGGCCAGAAA 18 12691

SCNNlA-8843 - AGAGGAGGCAGGCCAGAAA 19 12692

SCNNlA-8844 - GAGAGGAGGCAGGCCAGAAA 20 12693

SCNNlA-8845 - AGAGAGGAGGCAGGCCAGAAA 21 12694

SCNNlA-8846 - GAGAGAGGAGGCAGGCCAGAAA 22 12695

SCNNlA-8847 - AGAGAGAGGAGGCAGGCCAGAAA 23 12696

SCNNlA-8848 - UAGAGAGAGGAGGCAGGCCAGAAA 24 12697

SCNNlA-8849 - GAGAGACCCAAAGAGAAA 18 12698

SCNNlA-8850 - GGAGAGACCCAAAGAGAAA 19 12699

SCNNlA-8851 - AGGAGAGACCCAAAGAGAAA 20 12700

SCNNlA-8852 - CAGGAGAGACCCAAAGAGAAA 21 12701

SCNNlA-8853 - GCAGGAGAGACCCAAAGAGAAA 22 12702

SCNNlA-8854 - AGCAGGAGAGACCCAAAGAGAAA 23 12703

SCNNlA-8855 - GAGCAGGAGAGACCCAAAGAGAAA 24 12704

SCNNlA-8856 - CGAGGAAUCAGCAGGAAA 18 12705

SCNNlA-8857 - GCGAGGAAUCAGCAGGAAA 19 12706

SCNNlA-8858 - GGCGAGGAAUCAGCAGGAAA 20 12707

SCNNlA-8859 - UGGCGAGGAAUCAGCAGGAAA 21 12708

SCNNlA-8860 - GUGGCGAGGAAUCAGCAGGAAA 22 12709

SCNNlA-8861 - GGUGGCGAGGAAUCAGCAGGAAA 23 12710

SCNNlA-8862 - GG G U G G CG AG G AAU C AG CAG G AAA 24 12711

SCNNlA-8863 - CUGGAGGAAGAAGACCAA 18 12712

SCNNlA-8864 - CCUGGAGGAAGAAGACCAA 19 12713

SCNNlA-5519 - UCCUGGAGGAAGAAGACCAA 20 9368

SCNNlA-8865 - AUCCUGGAGGAAGAAGACCAA 21 12714

SCNNlA-8866 - GAUCCUGGAGGAAGAAGACCAA 22 12715

SCNNlA-8867 - AGAUCCUGGAGGAAGAAGACCAA 23 12716

SCNNlA-8868 - CAGAUCCUGGAGGAAGAAGACCAA 24 12717

SCNNlA-8869 - UCCAGCUGUCCCUUCCAA 18 12718

SCNNlA-8870 - AUCCAGCUGUCCCUUCCAA 19 12719

SCNNlA-5521 - AAUCCAGCUGUCCCUUCCAA 20 9370

SCNNlA-8871 - AAAUCCAGCUGUCCCUUCCAA 21 12720

SCNNlA-8872 - AAAAUCCAGCUGUCCCUUCCAA 22 12721

SCNNlA-8873 - AAAAAUCCAGCUGUCCCUUCCAA 23 12722

SCNNlA-8874 - GAAAAAUCCAGCUGUCCCUUCCAA 24 12723

1429

5535.1 SCNNlA-1790 - CAGUAUCAAGGUAAGCAA 18 5639

SCNNlA-1791 - G C AG U A U C A AG G U A AG C A A 19 5640

SCNNlA-393 - AGCAGUAUCAAGGUAAGCAA 20 4242

SCNNlA-1792 - GAGCAGUAUCAAGGUAAGCAA 21 5641

SCNNlA-1793 - UGAGCAGUAUCAAGGUAAGCAA 22 5642

SCNNlA-1794 - AUGAGCAGUAU C A AG G U A AG C A A 23 5643

SCNNlA-1795 - CAUGAGCAGUAUCAAGGUAAGCAA 24 5644

SCNNlA-8875 - CGCAAGAGACUGCCGCAA 18 12724

SCNNlA-8876 - UCGCAAGAGACUGCCGCAA 19 12725

SCNNlA-8877 - GUCGCAAGAGACUGCCGCAA 20 12726

SCNNlA-8878 - AGUCGCAAGAGACUGCCGCAA 21 12727

SCNNlA-8879 - AAG U CGCAAG AG ACUG CCG CAA 22 12728

SCNNlA-8880 - GAAGUCGCAAGAGACUGCCGCAA 23 12729

SCNNlA-8881 - AGAAGUCGCAAGAGACUGCCGCAA 24 12730

SCNNlA-8882 - UGAGAGGGGGCAAGGCAA 18 12731

SCNNlA-8883 - GUGAGAGGGGGCAAGGCAA 19 12732

SCNNlA-6079 - AGUGAGAGGGGGCAAGGCAA 20 9928

SCNNlA-8884 - GAGUGAGAGGGGGCAAGGCAA 21 12733

SCNNlA-8885 - AGAGUGAGAGGGGGCAAGGCAA 22 12734

SCNNlA-8886 - UAGAGUGAGAGGGGGCAAGGCAA 23 12735

SCNNlA-8887 - CUAGAGUGAGAGGGGGCAAGGCAA 24 12736

SCNNlA-8888 - UGUAAGGACCUGGCUCAA 18 12737

SCNNlA-8889 - AUGUAAGGACCUGGCUCAA 19 12738

SCNNlA-5522 - AAUGUAAGGACCUGGCUCAA 20 9371

SCNNlA-8890 - CAAUGUAAGGACCUGGCUCAA 21 12739

SCNNlA-8891 - CCAAUGUAAGGACCUGGCUCAA 22 12740

SCNNlA-8892 - CCCAAUGUAAGGACCUGGCUCAA 23 12741

SCNNlA-8893 - GCCCAAUGUAAGGACCUGGCUCAA 24 12742

SCNNlA-8894 - UUUGGCUGCCAGAUUCAA 18 12743

SCNNlA-8895 - GUUUGGCUGCCAGAUUCAA 19 12744

SCNNlA-8896 - GGUUUGGCUGCCAGAUUCAA 20 12745

SCNNlA-8897 - AGGUUUGGCUGCCAGAUUCAA 21 12746

SCNNlA-8898 - GAGGUUUGGCUGCCAGAUUCAA 22 12747

SCNNlA-8899 - AGAGGUUUGGCUGCCAGAUUCAA 23 12748

SCNNlA-8900 - GAGAGGUUUGGCUGCCAGAUUCAA 24 12749

SCNNlA-8901 - AAGGGGGCAGAGACAGAA 18 12750

SCNNlA-8902 - GAAGGGGGCAGAGACAGAA 19 12751

SCNNlA-5864 - GGAAGGGGGCAGAGACAGAA 20 9713

SCNNlA-8903 - AGGAAGGGGGCAGAGACAGAA 21 12752

SCNNlA-8904 - AAGGAAGGGGGCAGAGACAGAA 22 12753

SCNNlA-8905 - AAAGGAAGGGGGCAGAGACAGAA 23 12754

SCNNlA-8906 - CAAAGGAAGGGGGCAGAGACAGAA 24 12755

1430

5535.1 SCNNlA-8907 - GGAAGAAGACCAAAGGAA 18 12756

SCNNlA-8908 - AGGAAGAAGACCAAAGGAA 19 12757

SCNNlA-5865 - GAGGAAGAAGACCAAAGGAA 20 9714

SCNNlA-8909 - G G AG G AAG AAG ACCAAAG G AA 21 12758

SCNNlA-8910 - U G GAG G AAG AAG ACCAAAG GAA 22 12759

SCNNlA-8911 - CUGGAGGAAGAAGACCAAAGGAA 23 12760

SCNNlA-8912 - CCUGGAGGAAGAAGACCAAAGGAA 24 12761

SCNNlA-8913 - GCAAGGGGGGGAGAGGAA 18 12762

SCNNlA-8914 - GGCAAGGGGGGGAGAGGAA 19 12763

SCNNlA-8915 - AGGCAAGGGGGGGAGAGGAA 20 12764

SCNNlA-8916 - AAGGCAAGGGGGGGAGAGGAA 21 12765

SCNNlA-8917 - CAAGGCAAGGGGGGGAGAGGAA 22 12766

SCNNlA-8918 - GCAAGGCAAGGGGGGGAGAGGAA 23 12767

SCNNlA-8919 - GGCAAGGCAAGGGGGGGAGAGGAA 24 12768

SCNNlA-8920 - UGCCAGAUUCAACUGGAA 18 12769

SCNNlA-8921 - CUGCCAGAUUCAACUGGAA 19 12770

SCNNlA-5173 - GCUGCCAGAUUCAACUGGAA 20 9022

SCNNlA-8922 - GGCUGCCAGAUUCAACUGGAA 21 12771

SCNNlA-8923 - UGGCUGCCAGAUUCAACUGGAA 22 12772

SCNNlA-8924 - UUGGCUGCCAGAUUCAACUGGAA 23 12773

SCNNlA-8925 - UUUGGCUGCCAGAUUCAACUGGAA 24 12774

SCNNlA-1802 - CACUCCGGGGCUCAUGAA 18 5651

SCNNlA-1803 - CCACUCCGGGGCUCAUGAA 19 5652

SCNNlA-451 - UCCACUCCGGGGCUCAUGAA 20 4300

SCNNlA-1804 - AUCCACUCCGGGGCUCAUGAA 21 5653

SCNNlA-1805 - AAUCCACUCCGGGGCUCAUGAA 22 5654

SCNNlA-1806 - CAAUCCACUCCGGGGCUCAUGAA 23 5655

SCNNlA-1807 - CCAAUCCACUCCGGGGCUCAUGAA 24 5656

SCNNlA-8926 - CGCCCUGCUCACCUUUAA 18 12775

SCNNlA-8927 - CCGCCCUGCUCACCUUUAA 19 12776

SCNNlA-8928 - CCCGCCCUGCUCACCUUUAA 20 12777

SCNNlA-8929 - CCCCGCCCUGCUCACCUUUAA 21 12778

SCNNlA-8930 - CCCCCGCCCUGCUCACCUUUAA 22 12779

SCNNlA-8931 - CCCCCCGCCCUGCUCACCUUUAA 23 12780

SCNNlA-8932 - UCCCCCCGCCCUGCUCACCUUUAA 24 12781

SCNNlA-8933 - AGUUUCUUCAUUAGGACA 18 12782

SCNNlA-8934 - CAG U U U CU U CAU U AGG ACA 19 12783

SCNNlA-8935 - UCAGUUUCUUCAUUAGGACA 20 12784

SCNNlA-8936 - GUCAGUUUCUUCAUUAGGACA 21 12785

SCNNlA-8937 - GGUCAGUUUCUUCAUUAGGACA 22 12786

SCNNlA-8938 - GGGUCAGUUUCUUCAUUAGGACA 23 12787

SCNNlA-8939 - AGGGUCAGUUUCUUCAUUAGGACA 24 12788

1431

5535.1 SCNNlA-8940 - CCUGGAGGAAGAAGACCA 18 12789

SCNNlA-8941 - UCCUGGAGGAAGAAGACCA 19 12790

SCNNlA-8942 - AUCCUGGAGGAAGAAGACCA 20 12791

SCNNlA-8943 - GAUCCUGGAGGAAGAAGACCA 21 12792

SCNNlA-8944 - AGAUCCUGGAGGAAGAAGACCA 22 12793

SCNNlA-8945 - CAGAUCCUGGAGGAAGAAGACCA 23 12794

SCNNlA-8946 - ACAGAUCCUGGAGGAAGAAGACCA 24 12795

SCNNlA-8947 - GAGAUAACCCAGCACCCA 18 12796

SCNNlA-8948 - GGAGAUAACCCAGCACCCA 19 12797

SCNNlA-8949 - AGGAGAUAACCCAGCACCCA 20 12798

SCNNlA-8950 - AAGGAGAUAACCCAGCACCCA 21 12799

SCNNlA-8951 - CAAGGAGAUAACCCAGCACCCA 22 12800

SCNNlA-8952 - CCAAGGAGAUAACCCAGCACCCA 23 12801

SCNNlA-8953 - GCCAAGGAGAUAACCCAGCACCCA 24 12802

SCNNlA-8954 - GAGAGCAGGAGAGACCCA 18 12803

SCNNlA-8955 - GGAGAGCAGGAGAGACCCA 19 12804

SCNNlA-8956 - AGGAGAGCAGGAGAGACCCA 20 12805

SCNNlA-8957 - GAGGAGAGCAGGAGAGACCCA 21 12806

SCNNlA-8958 - AGAGGAGAGCAGGAGAGACCCA 22 12807

SCNNlA-8959 - AAGAGGAGAGCAGGAGAGACCCA 23 12808

SCNNlA-8960 - AAAGAGGAGAGCAGGAGAGACCCA 24 12809

SCNNlA-8961 - GCUAAGUAGAUAGCCCCA 18 12810

SCNNlA-8962 - CGCUAAGUAGAUAGCCCCA 19 12811

SCNNlA-8963 - GCGCUAAGUAGAUAGCCCCA 20 12812

SCNNlA-8964 - AGCGCUAAGUAGAUAGCCCCA 21 12813

SCNNlA-8965 - AAGCGCUAAGUAGAUAGCCCCA 22 12814

SCNNlA-8966 - AAAGCGCUAAGUAGAUAGCCCCA 23 12815

SCNNlA-8967 - AAAAGCGCUAAGUAGAUAGCCCCA 24 12816

SCNNlA-8968 - GACCUUUUCACAGAGCCA 18 12817

SCNNlA-8969 - AGACCUUUUCACAGAGCCA 19 12818

SCNNlA-5866 - GAGACCUUUUCACAGAGCCA 20 9715

SCNNlA-8970 - AGAGACCUUUUCACAGAGCCA 21 12819

SCNNlA-8971 - CAGAGACCUUUUCACAGAGCCA 22 12820

SCNNlA-8972 - GCAGAGACCUUU UCACAGAGCCA 23 12821

SCNNlA-8973 - UGCAGAG ACCU U U UCACAGAGCCA 24 12822

SCNNlA-8974 - UCCAUCCCUGGCCGGCCA 18 12823

SCNNlA-8975 - UUCCAUCCCUGGCCGGCCA 19 12824

SCNNlA-8976 - CUUCCAUCCCUGGCCGGCCA 20 12825

SCNNlA-8977 - GCUUCCAUCCCUGGCCGGCCA 21 12826

SCNNlA-8978 - CGCUUCCAUCCCUGGCCGGCCA 22 12827

SCNNlA-8979 - UCGCUUCCAUCCCUGGCCGGCCA 23 12828

SCNNlA-8980 - GUCGCUUCCAUCCCUGGCCGGCCA 24 12829

1432

5535.1 SCNNlA-8981 - AUCCAGCUGUCCCUUCCA 18 12830

SCNNlA-8982 - AAUCCAGCUGUCCCUUCCA 19 12831

SCNNlA-5531 - AAAUCCAGCUGUCCCUUCCA 20 9380

SCNNlA-8983 - AAAAUCCAGCUGUCCCUUCCA 21 12832

SCNNlA-8984 - AAAAAUCCAGCUGUCCCUUCCA 22 12833

SCNNlA-8985 - GAAAAAUCCAGCUGUCCCUUCCA 23 12834

SCNNlA-8986 - AGAAAAAUCCAGCUGUCCCUUCCA 24 12835

SCNNlA-8987 - GGCCCUAUCAGGGAAGCA 18 12836

SCNNlA-8988 - UGGCCCUAUCAGGGAAGCA 19 12837

SCNNlA-8989 - GUGGCCCUAUCAGGGAAGCA 20 12838

SCNNlA-8990 - GGUGGCCCUAUCAGGGAAGCA 21 12839

SCNNlA-8991 - AGGUGGCCCUAUCAGGGAAGCA 22 12840

SCNNlA-8992 - AAGGUGGCCCUAUCAGGGAAGCA 23 12841

SCNNlA-8993 - AAAGGUGGCCCUAUCAGGGAAGCA 24 12842

SCNNlA-1808 - GCAGUAUCAAGGUAAGCA 18 5657

SCNNlA-1809 - AGCAGUAUCAAGGUAAGCA 19 5658

SCNNlA-342 - GAGCAGUAUCAAGGUAAGCA 20 4191

SCNNlA-1810 - UGAGCAGUAUCAAGGUAAGCA 21 5659

SCNNlA-1811 - AUGAGCAGUAUCAAGGUAAGCA 22 5660

SCNNlA-1812 - CAUGAGCAGUAUCAAGGUAAGCA 23 5661

SCNNlA-1813 - UCAUGAGCAGUAUCAAGGUAAGCA 24 5662

SCNNlA-8994 - U G G C A A A U AG A A A AG G C A 18 12843

SCNNlA-8995 - C U G G C A A A U AG A A A AG G C A 19 12844

SCNNlA-5180 - G C U G G C A A A U AG A A A AG G C A 20 9029

SCNNlA-8996 - AG C U G G C A A A U AG A A A AG G C A 21 12845

SCNNlA-8997 - G AG C U G G C A A A U AG A A A AG G C A 22 12846

SCNNlA-8998 - UGAGCUGG C A A A U AG A A A AG G C A 23 12847

SCNNlA-8999 - AUGAGCUGGCAAAUAGAAAAGGCA 24 12848

SCNNlA-9000 - GUGAGAGGGGGCAAGGCA 18 12849

SCNNlA-9001 - AGUGAGAGGGGGCAAGGCA 19 12850

SCNNlA-5868 - GAGUGAGAGGGGGCAAGGCA 20 9717

SCNNlA-9002 - AGAGUGAGAGGGGGCAAGGCA 21 12851

SCNNlA-9003 - UAGAGUGAGAGGGGGCAAGGCA 22 12852

SCNNlA-9004 - CUAGAGUGAGAGGGGGCAAGGCA 23 12853

SCNNlA-9005 - CCUAGAGUGAGAGGGGGCAAGGCA 24 12854

SCNNlA-9006 - UCUGGGAUAUGUGGGGCA 18 12855

SCNNlA-9007 - CUCUGGGAUAUGUGGGGCA 19 12856

SCNNlA-9008 - UCUCUGGGAUAUGUGGGGCA 20 12857

SCNNlA-9009 - GUCUCUGGGAUAUGUGGGGCA 21 12858

SCNNlA-9010 - GGUCUCUGGGAUAUGUGGGGCA 22 12859

SCNNlA-9011 - GGGUCUCUGGGAUAUGUGGGGCA 23 12860

1433

5535.1 SCNNlA-9012 - GGGGUCUCUGGGAUAUGUGGGGCA 24

12861

SCNNlA-9013 - CUUCCUGAGUCUCCUGCA 18 12862

SCNNlA-9014 - GCUUCCUGAGUCUCCUGCA 19 12863

SCNNlA-9015 - GGCUUCCUGAGUCUCCUGCA 20 12864

SCNNlA-9016 - AGGCUUCCUGAGUCUCCUGCA 21 12865

SCNNlA-9017 - AAGGCUUCCUGAGUCUCCUGCA 22 12866

SCNNlA-9018 - GAAGGCUUCCUGAGUCUCCUGCA 23 12867

SCNNlA-9019 - GGAAGGCUUCCUGAGUCUCCUGCA 24 12868

SCNNlA-9020 - GCUGAGCACCUUAUUGCA 18 12869

SCNNlA-9021 - UGCUGAGCACCUUAUUGCA 19 12870

SCNNlA-5184 - GUGCUGAGCACCUUAUUGCA 20 9033

SCNNlA-9022 - GGUGCUGAGCACCUUAUUGCA 21 12871

SCNNlA-9023 - GGGUGCUGAGCACCUUAUUGCA 22 12872

SCNNlA-9024 - AGGGUGCUGAGCACCUUAUUGCA 23 12873

SCNNlA-9025 - CAGGGUGCUGAGCACCUUAUUGCA 24 12874

SCNNlA-9026 - CGAAAGGUGGCCCUAUCA 18 12875

SCNNlA-9027 - UCGAAAGGUGGCCCUAUCA 19 12876

SCNNlA-5540 - CUCGAAAGGUGGCCCUAUCA 20 9389

SCNNlA-9028 - ACUCGAAAGGUGGCCCUAUCA 21 12877

SCNNlA-9029 - AACUCGAAAGGUGGCCCUAUCA 22 12878

SCNNlA-9030 - AAACUCGAAAGGUGGCCCUAUCA 23 12879

SCNNlA-9031 - AAAACUCGAAAGGUGGCCCUAUCA 24 12880

SCNNlA-9032 - AUGUAAGGACCUGGCUCA 18 12881

SCNNlA-9033 - AAUGUAAGGACCUGGCUCA 19 12882

SCNNlA-5542 - CAAUGUAAGGACCUGGCUCA 20 9391

SCNNlA-9034 - CCAAUGUAAGGACCUGGCUCA 21 12883

SCNNlA-9035 - CCCAAUGUAAGGACCUGGCUCA 22 12884

SCNNlA-9036 - GCCCAAUGUAAGGACCUGGCUCA 23 12885

SCNNlA-9037 - UGCCCAAUGUAAGGACCUGGCUCA 24 12886

SCNNlA-1814 - AGCCCAUACCAGGUCUCA 18 5663

SCNNlA-1815 - CAGCCCAUACCAGGUCUCA 19 5664

SCNNlA-1 - GCAGCCCAUACCAGGUCUCA 20 503

SCNNlA-1816 - UGCAGCCCAUACCAGGUCUCA 21 5665

SCNNlA-1817 - CUGCAGCCCAUACCAGGUCUCA 22 5666

SCNNlA-1818 - UCUGCAGCCCAUACCAGGUCUCA 23 5667

SCNNlA-1819 - CUCUGCAGCCCAUACCAGGUCUCA 24 5668

SCNNlA-9038 - GCAUUGCAAUUCUUCUCA 18 12887

SCNNlA-9039 - GGCAUUGCAAUUCUUCUCA 19 12888

SCNNlA-9040 - AGGCAUUGCAAUUCUUCUCA 20 12889

SCNNlA-9041 - CAGGCAUUGCAAUUCUUCUCA 21 12890

SCNNlA-9042 - CCAGGCAUUGCAAUUCUUCUCA 22 12891

1434

5535.1 SCNNlA-9043 - ACCAGGCAUUGCAAUUCUUCUCA 23 12892

SCNNlA-9044 - GACCAGGCAUUGCAAUUCUUCUCA 24 12893

SCNNlA-9045 - AGUGCAGAGACCUUUUCA 18 12894

SCNNlA-9046 - CAGUGCAGAGACCUUUUCA 19 12895

SCNNlA-9047 - ACAGUGCAGAGACCUUUUCA 20 12896

SCNNlA-9048 - GACAGUGCAGAGACCUUUUCA 21 12897

SCNNlA-9049 - GGACAGUGCAGAGACCUUUUCA 22 12898

SCNNlA-9050 - GGGACAGUGCAGAGACCUUUUCA 23 12899

SCNNlA-9051 - GGGGACAGUGCAGAGACCUUUUCA 24 12900

SCNNlA-9052 - CAAGAGACUGCCGCAAGA 18 12901

SCNNlA-9053 - GCAAGAGACUGCCGCAAGA 19 12902

SCNNlA-9054 - CGCAAGAGACUGCCGCAAGA 20 12903

SCNNlA-9055 - UCGCAAGAGACUGCCGCAAGA 21 12904

SCNNlA-9056 - GUCGCAAGAGACUGCCGCAAGA 22 12905

SCNNlA-9057 - AGUCGCAAGAGACUGCCGCAAGA 23 12906

SCNNlA-9058 - AAGUCGCAAGAGACUGCCGCAAGA 24 12907

SCNNlA-9059 - GAAGGGGGCAGAGACAGA 18 12908

SCNNlA-9060 - GGAAGGGGGCAGAGACAGA 19 12909

SCNNlA-9061 - AGGAAGGGGGCAGAGACAGA 20 12910

SCNNlA-9062 - AAGGAAGGGGGCAGAGACAGA 21 12911

SCNNlA-9063 - AAAGGAAGGGGGCAGAGACAGA 22 12912

SCNNlA-9064 - CAAAGGAAGGGGGCAGAGACAGA 23 12913

SCNNlA-9065 - CCAAAGGAAGGGGGCAGAGACAGA 24 12914

SCNNlA-9066 - GAGAGGAGGCAGGCCAGA 18 12915

SCNNlA-9067 - AGAGAGGAGGCAGGCCAGA 19 12916

SCNNlA-9068 - GAGAGAGGAGGCAGGCCAGA 20 12917

SCNNlA-9069 - AGAGAGAGGAGGCAGGCCAGA 21 12918

SCNNlA-9070 - UAGAGAGAGGAGGCAGGCCAGA 22 12919

SCNNlA-9071 - UUAGAGAGAGGAGGCAGGCCAGA 23 12920

SCNNlA-9072 - AUUAGAGAGAGGAGGCAGGCCAGA 24 12921

SCNNlA-9073 - AGAGAAACAGAAGGCAGA 18 12922

SCNNlA-9074 - AAGAGAAACAGAAGGCAGA 19 12923

SCNNlA-9075 - AAAG AG AAAC AG AAG G C AG A 20 12924

SCNNlA-9076 - CAAAG AG AAAC AG AAG G C AG A 21 12925

SCNNlA-9077 - CCAAAGAGAAACAGAAGGCAGA 22 12926

SCNNlA-9078 - CCCAAAGAGAAACAGAAGGCAGA 23 12927

SCNNlA-9079 - ACCCAAAGAGAAACAGAAGGCAGA 24 12928

SCNNlA-9080 - AAAGGAAGGGGGCAGAGA 18 12929

SCNNlA-9081 - CAAAGGAAGGGGGCAGAGA 19 12930

SCNNlA-9082 - C C AAAG G A AG GGGGCAGAGA 20 12931

SCNNlA-9083 - ACCAAAGGAAGGGGGCAGAGA 21 12932

SCNNlA-9084 - GACCAAAGGAAGGGGGCAGAGA 22 12933

1435

5535.1 SCNNlA-9085 - AGACCAAAGGAAGGGGGCAGAGA 23 12934

SCNNlA-9086 - AAGACCAAAGGAAGGGGGCAGAGA 24 12935

SCNNlA-9087 - GAGAGGCAGGAUUAGAGA 18 12936

SCNNlA-9088 - AGAGAGGCAGGAUUAGAGA 19 12937

SCNNlA-9089 - AAGAGAGGCAGGAUUAGAGA 20 12938

SCNNlA-9090 - GAAGAGAGGCAGGAUUAGAGA 21 12939

SCNNlA-9091 - GGAAGAGAGGCAGGAUUAGAGA 22 12940

SCNNlA-9092 - AGGAAGAGAGGCAGGAUUAGAGA 23 12941

SCNNlA-9093 - GAGGAAGAGAGGCAGGAUUAGAGA 24 12942

SCNNlA-9094 - GACCUGGCUCAAGGGAGA 18 12943

SCNNlA-9095 - GGACCUGGCUCAAGGGAGA 19 12944

SCNNlA-9096 - AGGACCUGGCUCAAGGGAGA 20 12945

SCNNlA-9097 - AAGGACCUGGCUCAAGGGAGA 21 12946

SCNNlA-9098 - UAAGGACCUGGCUCAAGGGAGA 22 12947

SCNNlA-9099 - GUAAGGACCUGGCUCAAGGGAGA 23 12948

SCNNlA-9100 - UGUAAGGACCUGGCUCAAGGGAGA 24 12949

SCNNlA-9101 - UGAGGGCCUAGAGUGAGA 18 12950

SCNNlA-9102 - CUGAGGGCCUAGAGUGAGA 19 12951

SCNNlA-5188 - GCUGAGGGCCUAGAGUGAGA 20 9037

SCNNlA-9103 - AGCUGAGGGCCUAGAGUGAGA 21 12952

SCNNlA-9104 - GAGCUGAGGGCCUAGAGUGAGA 22 12953

SCNNlA-9105 - GGAGCUGAGGGCCUAGAGUGAGA 23 12954

SCNNlA-9106 - UGGAGCUGAGGGCCUAGAGUGAGA 24 12955

SCNNlA-9107 - AAACAGAAGGCAGAUAGA 18 12956

SCNNlA-9108 - GAAACAGAAGGCAGAUAGA 19 12957

SCNNlA-9109 - AGAAACAGAAGGCAGAUAGA 20 12958

SCNNlA-9110 - GAGAAACAGAAGGCAGAUAGA 21 12959

SCNNlA-9111 - AGAGAAACAGAAGGCAGAUAGA 22 12960

SCNNlA-9112 - AAG AG AAACAGAAGGCAGAUAGA 23 12961

SCNNlA-9113 - AAAGAGAAACAGAAGGCAGAUAGA 24 12962

SCNNlA-9114 - UGGAGCUGAGGGCCUAGA 18 12963

SCNNlA-9115 - CUGGAGCUGAGGGCCUAGA 19 12964

SCNNlA-9116 - GCUGGAGCUGAGGGCCUAGA 20 12965

SCNNlA-9117 - GGCUGGAGCUGAGGGCCUAGA 21 12966

SCNNlA-9118 - AGGCUGGAGCUGAGGGCCUAGA 22 12967

SCNNlA-9119 - GAGGCUGGAGCUGAGGGCCUAGA 23 12968

SCNNlA-9120 - AGAGGCUGGAGCUGAGGGCCUAGA 24 12969

SCNNlA-9121 - AAGAGAGGCAGGAUUAGA 18 12970

SCNNlA-9122 - GAAGAGAGGCAGGAUUAGA 19 12971

SCNNlA-9123 - GGAAGAGAGGCAGGAUUAGA 20 12972

SCNNlA-9124 - AGGAAGAGAGGCAGGAUUAGA 21 12973

SCNNlA-9125 - GAGGAAGAGAGGCAGGAUUAGA 22 12974

1436

5535.1 SCNNlA-9126 - AGAGGAAGAGAGGCAGGAUUAGA 23 12975

SCNNlA-9127 - GAGAGGAAGAGAGGCAGGAUUAGA 24 12976

SCNNlA-9128 - AGGAAGAAGACCAAAGGA 18 12977

SCNNlA-9129 - GAGGAAGAAGACCAAAGGA 19 12978

SCNNlA-5873 - GGAGGAAGAAGACCAAAGGA 20 9722

SCNNlA-9130 - UGGAGGAAGAAGACCAAAGGA 21 12979

SCNNlA-9131 - CUGGAGGAAGAAGACCAAAGGA 22 12980

SCNNlA-9132 - CCUGGAGGAAGAAGACCAAAGGA 23 12981

SCNNlA-9133 - UCCUGGAGGAAGAAGACCAAAGGA 24 12982

SCNNlA-9134 - GGCGAGGAAUCAGCAGGA 18 12983

SCNNlA-9135 - UGGCGAGGAAUCAGCAGGA 19 12984

SCNNlA-9136 - GUGGCGAGGAAUCAGCAGGA 20 12985

SCNNlA-9137 - GGUGGCGAGGAAUCAGCAGGA 21 12986

SCNNlA-9138 - GGGUGGCGAGGAAUCAGCAGGA 22 12987

SCNNlA-9139 - GGGGUGGCGAGGAAUCAGCAGGA 23 12988

SCNNlA-9140 - GGGGGUGGCGAGGAAUCAGCAGGA 24 12989

SCNNlA-9141 - UGGAGGAGGGAGGGAGGA 18 12990

SCNNlA-9142 - GUGGAGGAGGGAGGGAGGA 19 12991

SCNNlA-9143 - GGUGGAGGAGGGAGGGAGGA 20 12992

SCNNlA-9144 - AGGUGGAGGAGGGAGGGAGGA 21 12993

SCNNlA-9145 - AAGGUGGAGGAGGGAGGGAGGA 22 12994

SCNNlA-9146 - AAAGGUGGAGGAGGGAGGGAGGA 23 12995

SCNNlA-9147 - GAAAGGUGGAGGAGGGAGGGAGGA 24

12996

SCNNlA-9148 - UCCAGGAAAGGUGGAGGA 18 12997

SCNNlA-9149 - CUCCAGGAAAGGUGGAGGA 19 12998

SCNNlA-5877 - GCUCCAGGAAAGGUGGAGGA 20 9726

SCNNlA-9150 - GGCUCCAGGAAAGGUGGAGGA 21 12999

SCNNlA-9151 - UGGCUCCAGGAAAGGUGGAGGA 22 13000

SCNNlA-9152 - CUGGCUCCAGGAAAGGUGGAGGA 23 13001

SCNNlA-9153 - GCUGGCUCCAGGAAAGGUGGAGGA 24 13002

SCNNlA-9154 - AAGGCAGAUAGAGAGGGA 18 13003

SCNNlA-9155 - GAAGGCAGAUAGAGAGGGA 19 13004

SCNNlA-9156 - AGAAGGCAGAUAGAGAGGGA 20 13005

SCNNlA-9157 - CAGAAGGCAGAUAGAGAGGGA 21 13006

SCNNlA-9158 - ACAGAAGGCAGAUAGAGAGGGA 22 13007

SCNNlA-9159 - AACAGAAGGCAGAUAGAGAGGGA 23 13008

SCNNlA-9160 - AAA CAGAAGGCAGAUAGAGAGGGA 24 13009

SCNNlA-9161 - GGAAAGGUGGAGGAGGGA 18 13010

SCNNlA-9162 - AGGAAAGGUGGAGGAGGGA 19 13011

SCNNlA-6095 - CAGGAAAGGUGGAGGAGGGA 20 9944

SCNNlA-9163 - CCAGGAAAGGUGGAGGAGGGA 21 13012

1437

5535.1 SCNNlA-9164 - UCCAGGAAAGGUGGAGGAGGGA 22 13013

SCNNlA-9165 - CUCCAGGAAAGGUGGAGGAGGGA 23 13014

SCNNlA-9166 - GCUCCAGGAAAGGUGGAGGAGGGA 24 13015

SCNNlA-9167 - GGCAAGGCAAGGGGGGGA 18 13016

SCNNlA-9168 - GGGCAAGGCAAGGGGGGGA 19 13017

SCNNlA-9169 - GGGGCAAGGCAAGGGGGGGA 20 13018

SCNNlA-9170 - GGGGGCAAGGCAAGGGGGGGA 21 13019

SCNNlA-9171 - AGGGGGCAAGGCAAGGGGGGGA 22 13020

SCNNlA-9172 - GAGGGGGCAAGGCAAGGGGGGGA 23 13021

SCNNlA-9173 - AGAGGGGGCAAGGCAAGGGGGGGA 24

13022

SCNNlA-1820 - GUUCCAGGGGUGAUGGGA 18 5669

SCNNlA-1821 - GGUUCCAGGGGUGAUGGGA 19 5670

SCNNlA-1822 - GGGUUCCAGGGGUGAUGGGA 20 5671

SCNNlA-1823 - CGGGUUCCAGGGGUGAUGGGA 21 5672

SCNNlA-1824 - UCGGGUUCCAGGGGUGAUGGGA 22 5673

SCNNlA-1825 - CUCGGGUUCCAGGGGUGAUGGGA 23 5674

SCNNlA-1826 - ACUCGGGUUCCAGGGGUGAUGGGA 24 5675

SCNNlA-9174 - UCCAGCCGCAACCUGGGA 18 13023

SCNNlA-9175 - GUCCAGCCGCAACCUGGGA 19 13024

SCNNlA-9176 - AGUCCAGCCGCAACCUGGGA 20 13025

SCNNlA-9177 - CAGUCCAGCCGCAACCUGGGA 21 13026

SCNNlA-9178 - CCAGUCCAGCCGCAACCUGGGA 22 13027

SCNNlA-9179 - CCCAGUCCAGCCGCAACCUGGGA 23 13028

SCNNlA-9180 - UCCCAGUCCAGCCGCAACCUGGGA 24 13029

SCNNlA-9181 - CACGGGCUCUGUGUGGGA 18 13030

SCNNlA-9182 - CCACGGGCUCUGUGUGGGA 19 13031

SCNNlA-9183 - UCCACGGGCUCUGUGUGGGA 20 13032

SCNNlA-9184 - AUCCACGGGCUCUGUGUGGGA 21 13033

SCNNlA-9185 - AAUCCACGGGCUCUGUGUGGGA 22 13034

SCNNlA-9186 - GAAUCCACGGGCUCUGUGUGGGA 23 13035

SCNNlA-9187 - CGAAUCCACGGGCUCUGUGUGGGA 24 13036

SCNNlA-1827 - CAUACCAGGUCUCAUGGA 18 5676

SCNNlA-1828 - CCAUACCAGGUCUCAUGGA 19 5677

SCNNlA-3 - CCCAUACCAGGUCUCAUGGA 20 556

SCNNlA-1829 - GCCCAUACCAGGUCUCAUGGA 21 5678

SCNNlA-1830 - AGCCCAUACCAGGUCUCAUGGA 22 5679

SCNNlA-1831 - CAGCCCAUACCAGGUCUCAUGGA 23 5680

SCNNlA-1832 - GCAGCCCAUACCAGGUCUCAUGGA 24 5681

SCNNlA-9188 - CUGCCAGAUUCAACUGGA 18 13037

SCNNlA-9189 - GCUGCCAGAUUCAACUGGA 19 13038

SCNNlA-9190 - GGCUGCCAGAUUCAACUGGA 20 13039

1438

5535.1 SCNNlA-9191 - UGGCUGCCAGAUUCAACUGGA 21 13040

SCNNlA-9192 - UUGGCUGCCAGAUUCAACUGGA 22 13041

SCNNlA-9193 - UUUGGCUGCCAGAUUCAACUGGA 23 13042

SCNNlA-9194 - GUUUGGCUGCCAGAUUCAACUGGA 24 13043

SCNNlA-9195 - UGUCUGCUGGCUUGUGGA 18 13044

SCNNlA-9196 - UUGUCUGCUGGCUUGUGGA 19 13045

SCNNlA-5552 - UUUGUCUGCUGGCUUGUGGA 20 9401

SCNNlA-9197 - CUUUGUCUGCUGGCUUGUGGA 21 13046

SCNNlA-9198 - CCUUUGUCUGCUGGCUUGUGGA 22 13047

SCNNlA-9199 - GCCUUUGUCUGCUGGCUUGUGGA 23 13048

SCNNlA-9200 - GGCCUUUGUCUGCUGGCUUGUGGA 24

13049

SCNNlA-9201 - UGCUGCAUUAAGUUUGGA 18 13050

SCNNlA-9202 - UUGCUGCAUUAAGUUUGGA 19 13051

SCNNlA-9203 - UUUGCUGCAUUAAGUUUGGA 20 13052

SCNNlA-9204 - UUUUGCUGCAUUAAGUUUGGA 21 13053

SCNNlA-9205 - CUUUUGCUGCAUUAAGUUUGGA 22 13054

SCNNlA-9206 - CCUUUUGCUGCAUUAAGUUUGGA 23 13055

SCNNlA-9207 - UCCUUUUGCUGCAUUAAGUUUGGA 24 13056

SCNNlA-1839 - CCACUCCGGGGCUCAUGA 18 5688

SCNNlA-1840 - UCCACUCCGGGGCUCAUGA 19 5689

SCNNlA-400 - AUCCACUCCGGGGCUCAUGA 20 4249

SCNNlA-1841 - AAUCCACUCCGGGGCUCAUGA 21 5690

SCNNlA-1842 - CAAUCCACUCCGGGGCUCAUGA 22 5691

SCNNlA-1843 - CCAAUCCACUCCGGGGCUCAUGA 23 5692

SCNNlA-1844 - CCCAAUCCACUCCGGGGCUCAUGA 24 5693

SCNNlA-9208 - GCUGAGGGCCUAGAGUGA 18 13057

SCNNlA-9209 - AGCUGAGGGCCUAGAGUGA 19 13058

SCNNlA-9210 - GAGCUGAGGGCCUAGAGUGA 20 13059

SCNNlA-9211 - GGAGCUGAGGGCCUAGAGUGA 21 13060

SCNNlA-9212 - UGGAGCUGAGGGCCUAGAGUGA 22 13061

SCNNlA-9213 - CUGGAGCUGAGGGCCUAGAGUGA 23 13062

SCNNlA-9214 - GCUGGAGCUGAGGGCCUAGAGUGA 24 13063

SCNNlA-9215 - GGCUCUGUGUGGGAGUGA 18 13064

SCNNlA-9216 - GGGCUCUGUGUGGGAGUGA 19 13065

SCNNlA-5555 - CGGGCUCUGUGUGGGAGUGA 20 9404

SCNNlA-9217 - ACGGGCUCUGUGUGGGAGUGA 21 13066

SCNNlA-9218 - CACGGGCUCUGUGUGGGAGUGA 22 13067

SCNNlA-9219 - CCACGGGCUCUGUGUGGGAGUGA 23 13068

SCNNlA-9220 - UCCACGGGCUCUGUGUGGGAGUGA 24 13069

SCNNlA-9221 - GCUGCUCCCACUUAGUGA 18 13070

SCNNlA-9222 - CGCUGCUCCCACUUAGUGA 19 13071

1439

5535.1 SCNNlA-9223 - GCGCUGCUCCCACUUAGUGA 20 13072

SCNNlA-9224 - UGCGCUGCUCCCACUUAGUGA 21 13073

SCNNlA-9225 - GUGCGCUGCUCCCACUUAGUGA 22 13074

SCNNlA-9226 - AGUGCGCUGCUCCCACUUAGUGA 23 13075

SCNNlA-9227 - GAGUGCGCUGCUCCCACUUAGUGA 24 13076

SCNNlA-9228 - GCUGCACCUGUCAGGUGA 18 13077

SCNNlA-9229 - CGCUGCACCUGUCAGGUGA 19 13078

SCNNlA-5556 - CCGCUGCACCUGUCAGGUGA 20 9405

SCNNlA-9230 - GCCGCUGCACCUGUCAGGUGA 21 13079

SCNNlA-9231 - GGCCGCUGCACCUGUCAGGUGA 22 13080

SCNNlA-9232 - AGGCCGCUGCACCUGUCAGGUGA 23 13081

SCNNlA-9233 - CAGGCCGCUGCACCUGUCAGGUGA 24 13082

SCNNlA-1845 - CUCGGGUUCCAGGGGUGA 18 5694

SCNNlA-1846 - ACUCGGGUUCCAGGGGUGA 19 5695

SCNNlA-401 - CACUCGGGUUCCAGGGGUGA 20 4250

SCNNlA-1847 - UCACUCGGGUUCCAGGGGUGA 21 5696

SCNNlA-1848 - CUCACUCGGGUUCCAGGGGUGA 22 5697

SCNNlA-1849 - CCUCACUCGGGUUCCAGGGGUGA 23 5698

SCNNlA-1850 - GCCUCACUCGGGUUCCAGGGGUGA 24 5699

SCNNlA-9234 - AGAAACAGAAGGCAGAUA 18 13083

SCNNlA-9235 - GAGAAACAGAAGGCAGAUA 19 13084

SCNNlA-9236 - AG AGAAACAGAAGGCAGAUA 20 13085

SCNNlA-9237 - AAGAGAAACAGAAGGCAGAUA 21 13086

SCNNlA-9238 - AAAG AGAAACAGAAGGCAGAUA 22 13087

SCNNlA-9239 - CAAAG AGAAACAGAAGGCAGAUA 23 13088

SCNNlA-9240 - CCAAAGAGAAACAGAAGGCAGAUA 24 13089

SCNNlA-9241 - CCUUUAAUUGAGAUGCUA 18 13090

SCNNlA-9242 - ACCUUUAAUUGAGAUGCUA 19 13091

SCNNlA-9243 - CACCUUUAAUUGAGAUGCUA 20 13092

SCNNlA-9244 - UCACCUUUAAUUGAGAUGCUA 21 13093

SCNNlA-9245 - CUCACCUUUAAUUGAGAUGCUA 22 13094

SCNNlA-9246 - GCUCACCUUUAAUUGAGAUGCUA 23 13095

SCNNlA-9247 - UGCUCACCUUUAAUUGAGAUGCUA 24 13096

SCNNlA-9248 - AGAGGAGAGGCCGUUCUA 18 13097

SCNNlA-9249 - CAGAGGAGAGGCCGUUCUA 19 13098

SCNNlA-5199 - GCAGAGGAGAGGCCGUUCUA 20 9048

SCNNlA-9250 - AGCAGAGGAGAGGCCGUUCUA 21 13099

SCNNlA-9251 - AAGCAGAGGAGAGGCCGUUCUA 22 13100

SCNNlA-9252 - GAAGCAGAGGAGAGGCCGUUCUA 23 13101

SCNNlA-9253 - GGAAGCAGAGGAGAGGCCGUUCUA 24 13102

SCNNlA-9254 - GGAAGAGAGGCAGGAUUA 18 13103

SCNNlA-9255 - AGGAAGAGAGGCAGGAUUA 19 13104

1440

5535.1 SCNNlA-9256 - GAGGAAGAGAGGCAGGAUUA 20 13105

SCNNlA-9257 - AGAGGAAGAGAGGCAGGAUUA 21 13106

SCNNlA-9258 - GAGAGGAAGAGAGGCAGGAUUA 22 13107

SCNNlA-9259 - GGAGAGGAAGAGAGGCAGGAUUA 23 13108

SCNNlA-9260 - GGGAGAGGAAGAGAGGCAGGAUUA 24

13109

SCNNlA-9261 - GUGCGCUGCUCCCACUUA 18 13110

SCNNlA-9262 - AGUGCGCUGCUCCCACUUA 19 13111

SCNNlA-9263 - GAGUGCGCUGCUCCCACUUA 20 13112

SCNNlA-9264 - UGAGUGCGCUGCUCCCACUUA 21 13113

SCNNlA-9265 - CUGAGUGCGCUGCUCCCACUUA 22 13114

SCNNlA-9266 - CCUGAGUGCGCUGCUCCCACUUA 23 13115

SCNNlA-9267 - ACCUGAGUGCGCUGCUCCCACUUA 24 13116

SCNNlA-9268 - GAGGUGCUAGGACAAAAC 18 13117

SCNNlA-9269 - GGAGGUGCUAGGACAAAAC 19 13118

SCNNlA-9270 - GGGAGGUGCUAGGACAAAAC 20 13119

SCNNlA-9271 - AGGGAGGUGCUAGGACAAAAC 21 13120

SCNNlA-9272 - AAGGGAGGUGCUAGGACAAAAC 22 13121

SCNNlA-9273 - AAAGGGAGGUGCUAGGACAAAAC 23 13122

SCNNlA-9274 - GAAAGGGAGGUGCUAGGACAAAAC 24 13123

SCNNlA-9275 - UCCCAGUCCAGCCGCAAC 18 13124

SCNNlA-9276 - GUCCCAGUCCAGCCGCAAC 19 13125

SCNNlA-9277 - AGUCCCAGUCCAGCCGCAAC 20 13126

SCNNlA-9278 - CAG U CCCAG U CCAGCCG CAAC 21 13127

SCNNlA-9279 - CCAGUCCCAGUCCAGCCGCAAC 22 13128

SCNNlA-9280 - ACCAGUCCCAGUCCAGCCGCAAC 23 13129

SCNNlA-9281 - AACCAG UCCCAGUCCAGCCGCAAC 24 13130

SCNNlA-9282 - UUGGCUGCCAGAUUCAAC 18 13131

SCNNlA-9283 - UUUGGCUGCCAGAUUCAAC 19 13132

SCNNlA-5202 - GUUUGGCUGCCAGAUUCAAC 20 9051

SCNNlA-9284 - GGUUUGGCUGCCAGAUUCAAC 21 13133

SCNNlA-9285 - AGGUUUGGCUGCCAGAUUCAAC 22 13134

SCNNlA-9286 - GAGGUUUGGCUGCCAGAUUCAAC 23 13135

SCNNlA-9287 - AGAGGUUUGGCUGCCAGAUUCAAC 24 13136

SCNNlA-9288 - UAGCUCCUGGAAGCACAC 18 13137

SCNNlA-9289 - CUAGCUCCUGGAAGCACAC 19 13138

SCNNlA-9290 - UCUAGCUCCUGGAAGCACAC 20 13139

SCNNlA-9291 - CUCUAGCUCCUGGAAGCACAC 21 13140

SCNNlA-9292 - CCUCUAGCUCCUGGAAGCACAC 22 13141

SCNNlA-9293 - GCCUCUAGCUCCUGGAAGCACAC 23 13142

SCNNlA-9294 - AGCCUCUAGCUCCUGGAAGCACAC 24 13143

SCNNlA-9295 - UUUCACAUCCAGGUGCAC 18 13144

1441

5535.1 SCNNlA-9296 - CUUUCACAUCCAGGUGCAC 19 13145

SCNNlA-9297 - GCUUUCACAUCCAGGUGCAC 20 13146

SCNNlA-9298 - GGCUUUCACAUCCAGGUGCAC 21 13147

SCNNlA-9299 - CGGCUUUCACAUCCAGGUGCAC 22 13148

SCNNlA-9300 - CCGGCUUUCACAUCCAGGUGCAC 23 13149

SCNNlA-9301 - CCCGGCUUUCACAUCCAGGUGCAC 24 13150

SCNNlA-9302 - CCUAGCCCCCAGCUUCAC 18 13151

SCNNlA-9303 - GCCUAGCCCCCAGCUUCAC 19 13152

SCNNlA-9304 - CGCCUAGCCCCCAGCUUCAC 20 13153

SCNNlA-9305 - CCGCCUAGCCCCCAGCUUCAC 21 13154

SCNNlA-9306 - CCCGCCUAGCCCCCAGCUUCAC 22 13155

SCNNlA-9307 - CCCCGCCUAGCCCCCAGCUUCAC 23 13156

SCNNlA-9308 - GCCCCGCCUAGCCCCCAGCUUCAC 24 13157

SCNNlA-9309 - GCAGGAAAGAGGAGGGAC 18 13158

SCNNlA-9310 - AGCAGGAAAGAGGAGGGAC 19 13159

SCNNlA-9311 - CAGCAGGAAAGAGGAGGGAC 20 13160

SCNNlA-9312 - UCAGCAGGAAAGAGGAGGGAC 21 13161

SCNNlA-9313 - AUCAGCAGGAAAGAGGAGGGAC 22 13162

SCNNlA-9314 - AAUCAGCAGGAAAGAGGAGGGAC 23 13163

SCNNlA-9315 - GAAUCAGCAGGAAAGAGGAGGGAC 24 13164

SCNNlA-1863 - GUGGGCGCAGGGUGGGAC 18 5712

SCNNlA-1864 - UGUGGGCGCAGGGUGGGAC 19 5713

SCNNlA-1865 - AUGUGGGCGCAGGGUGGGAC 20 5714

SCNNlA-1866 - AAUGUGGGCGCAGGGUGGGAC 21 5715

SCNNlA-1867 - GAAUGUGGGCGCAGGGUGGGAC 22 5716

SCNNlA-1868 - AGAAUGUGGGCGCAGGGUGGGAC 23 5717

SCNNlA-1869 - GAGAAUGUGGGCGCAGGGUGGGAC 24

5718

SCNNlA-9316 - CCCAG U CCAG CCG CAACC 18 13165

SCNNlA-9317 - UCCCAGUCCAGCCGCAACC 19 13166

SCNNlA-5213 - GUCCCAGUCCAGCCGCAACC 20 9062

SCNNlA-9318 - AG U CCCAG U CCAG CCG CAACC 21 13167

SCNNlA-9319 - CAG U CCCAG U CCAG CCG CAACC 22 13168

SCNNlA-9320 - CCAG UCCCAGUCCAGCCGCAACC 23 13169

SCNNlA-9321 - ACCAGUCCCAGUCCAGCCGCAACC 24 13170

SCNNlA-9322 - AGGAGAUAACCCAGCACC 18 13171

SCNNlA-9323 - AAGGAGAUAACCCAGCACC 19 13172

SCNNlA-9324 - CAAGGAGAUAACCCAGCACC 20 13173

SCNNlA-9325 - CCAAGGAGAUAACCCAGCACC 21 13174

SCNNlA-9326 - GCCAAGGAGAUAACCCAGCACC 22 13175

SCNNlA-9327 - AGCCAAGGAGAUAACCCAGCACC 23 13176

SCNNlA-9328 - GAGCCAAGGAGAUAACCCAGCACC 24 13177

1442

5535.1 SCNNlA-9329 - CAGGAAAGAGGAGGGACC 18 13178

SCNNlA-9330 - GCAGGAAAGAGGAGGGACC 19 13179

SCNNlA-5571 - AGCAGGAAAGAGGAGGGACC 20 9420

SCNNlA-9331 - CAGCAGGAAAGAGGAGGGACC 21 13180

SCNNlA-9332 - UCAGCAGGAAAGAGGAGGGACC 22 13181

SCNNlA-9333 - AUCAGCAGGAAAGAGGAGGGACC 23 13182

SCNNlA-9334 - AAUCAGCAGGAAAGAGGAGGGACC 24 13183

SCNNlA-9335 - CACAGACCAGGUUGGACC 18 13184

SCNNlA-9336 - CCACAGACCAGGUUGGACC 19 13185

SCNNlA-9337 - GCCACAGACCAGGUUGGACC 20 13186

SCNNlA-9338 - AGCCACAG ACCAGG U UGG ACC 21 13187

SCNNlA-9339 - AAGCCACAGACCAGGUUGGACC 22 13188

SCNNlA-9340 - GAAGCCACAGACCAGGUUGGACC 23 13189

SCNNlA-9341 - GGAAGCCACAGACCAGGUUGGACC 24 13190

SCNNlA-9342 - GCGCUAAGUAGAUAGCCC 18 13191

SCNNlA-9343 - AGCGCUAAGUAGAUAGCCC 19 13192

SCNNlA-9344 - AAGCGCUAAGUAGAUAGCCC 20 13193

SCNNlA-9345 - AAAGCGCUAAGUAGAUAGCCC 21 13194

SCNNlA-9346 - AAAAGCGCUAAGUAGAUAGCCC 22 13195

SCNNlA-9347 - C A A A AG CGCUAAGUAGAUAGCCC 23 13196

SCNNlA-9348 - GCAAAAGCGCUAAGUAGAUAGCCC 24 13197

SCNNlA-9349 - CUGCCUCCUGUGGGGCCC 18 13198

SCNNlA-9350 - GCUGCCUCCUGUGGGGCCC 19 13199

SCNNlA-9351 - GGCUGCCUCCUGUGGGGCCC 20 13200

SCNNlA-9352 - GGGCUGCCUCCUGUGGGGCCC 21 13201

SCNNlA-9353 - UGGGCUGCCUCCUGUGGGGCCC 22 13202

SCNNlA-9354 - CUGGGCUGCCUCCUGUGGGGCCC 23 13203

SCNNlA-9355 - UCUGGGCUGCCUCCUGUGGGGCCC 24 13204

SCNNlA-9356 - CUCCCAGUUCACCUGCCC 18 13205

SCNNlA-9357 - ACUCCCAGUUCACCUGCCC 19 13206

SCNNlA-9358 - UACUCCCAGUUCACCUGCCC 20 13207

SCNNlA-9359 - GUACUCCCAGUUCACCUGCCC 21 13208

SCNNlA-9360 - AGUACUCCCAGUUCACCUGCCC 22 13209

SCNNlA-9361 - CAGUACUCCCAGUUCACCUGCCC 23 13210

SCNNlA-9362 - CCAGUACUCCCAGUUCACCUGCCC 24 13211

SCNNlA-9363 - GCUGACCUGUGGGUGCCC 18 13212

SCNNlA-9364 - GGCUGACCUGUGGGUGCCC 19 13213

SCNNlA-9365 - AGGCUGACCUGUGGGUGCCC 20 13214

SCNNlA-9366 - GAGGCUGACCUGUGGGUGCCC 21 13215

SCNNlA-9367 - UGAGGCUGACCUGUGGGUGCCC 22 13216

SCNNlA-9368 - GUGAGGCUGACCUGUGGGUGCCC 23 13217

SCNNlA-9369 - GGUGAGGCUGACCUGUGGGUGCCC 24 13218

1443

5535.1 SCNNlA-9370 - AGACCUUUUCACAGAGCC 18 13219

SCNNlA-9371 - GAG ACCU U U U CACAG AG CC 19 13220

SCNNlA-9372 - AGAGACCUUUUCACAGAGCC 20 13221

SCNNlA-9373 - CAG AG ACCU U U U CACAG AGCC 21 13222

SCNNlA-9374 - GCAGAGACCUUUUCACAGAGCC 22 13223

SCNNlA-9375 - UGCAGAG ACCU U U UCACAGAGCC 23 13224

SCNNlA-9376 - G UGCAGAG ACCU U U UCACAGAGCC 24 13225

SCNNlA-1876 - GAGAGGGCACUCAGGGCC 18 5725

SCNNlA-1877 - GGAGAGGGCACUCAGGGCC 19 5726

SCNNlA-1878 - GGGAGAGGGCACUCAGGGCC 20 5727

SCNNlA-1879 - UGGGAGAGGGCACUCAGGGCC 21 5728

SCNNlA-1880 - AUGGGAGAGGGCACUCAGGGCC 22 5729

SCNNlA-1881 - GAUGGGAGAGGGCACUCAGGGCC 23 5730

SCNNlA-1882 - UGAUGGGAGAGGGCACUCAGGGCC 24 5731

SCNNlA-1889 - UGGGACAUGGGCAUGGCC 18 5738

SCNNlA-1890 - GUGGGACAUGGGCAUGGCC 19 5739

SCNNlA-347 - GGUGGGACAUGGGCAUGGCC 20 4196

SCNNlA-1891 - GGGUGGGACAUGGGCAUGGCC 21 5740

SCNNlA-1892 - AGGGUGGGACAUGGGCAUGGCC 22 5741

SCNNlA-1893 - CAGGGUGGGACAUGGGCAUGGCC 23 5742

SCNNlA-1894 - GCAGGGUGGGACAUGGGCAUGGCC 24 5743

SCNNlA-9377 - CAGAGAGCAGACGAAUCC 18 13226

SCNNlA-9378 - CCAGAGAGCAGACGAAUCC 19 13227

SCNNlA-9379 - CCCAGAGAGCAGACGAAUCC 20 13228

SCNNlA-9380 - ACCCAGAGAGCAGACGAAUCC 21 13229

SCNNlA-9381 - CACCCAGAGAGCAGACGAAUCC 22 13230

SCNNlA-9382 - GCACCCAGAGAGCAGACGAAUCC 23 13231

SCNNlA-9383 - AGCACCCAGAGAGCAGACGAAUCC 24 13232

SCNNlA-9384 - GAGCUGAGACACAGAUCC 18 13233

SCNNlA-9385 - GGAGCUGAGACACAGAUCC 19 13234

SCNNlA-5588 - AGGAGCUGAGACACAGAUCC 20 9437

SCNNlA-9386 - CAGGAGCUGAGACACAGAUCC 21 13235

SCNNlA-9387 - GCAGGAGCUGAGACACAGAUCC 22 13236

SCNNlA-9388 - GGCAGGAGCUGAGACACAGAUCC 23 13237

SCNNlA-9389 - AGGCAGGAGCUGAGACACAGAUCC 24 13238

SCNNlA-9390 - CAG AAAACUG AU U U AU CC 18 13239

SCNNlA-9391 - UCAGAAAACUGAUUUAUCC 19 13240

SCNNlA-9392 - CUCAGAAAACUGAUUUAUCC 20 13241

SCNNlA-9393 - CCUCAGAAAACUGAUUUAUCC 21 13242

SCNNlA-9394 - ACCUCAGAAAACUGAUUUAUCC 22 13243

SCNNlA-9395 - AACCUCAGAAAACUGAUUUAUCC 23 13244

SCNNlA-9396 - UAACCUCAGAAAACUGAUUUAUCC 24 13245

1444

5535.1 SCNNlA-9397 - GAGGCAGCCCAGACCUCC 18 13246

SCNNlA-9398 - GGAGGCAGCCCAGACCUCC 19 13247

SCNNlA-5591 - UGGAGGCAGCCCAGACCUCC 20 9440

SCNNlA-9399 - CUGGAGGCAGCCCAGACCUCC 21 13248

SCNNlA-9400 - GCUGGAGGCAGCCCAGACCUCC 22 13249

SCNNlA-9401 - AGCUGGAGGCAGCCCAGACCUCC 23 13250

SCNNlA-9402 - AAGCUGGAGGCAGCCCAGACCUCC 24 13251

SCNNlA-9403 - ACGAAUUUCUCCUCCUCC 18 13252

SCNNlA-9404 - AACGAAUUUCUCCUCCUCC 19 13253

SCNNlA-9405 - CAACGAAUUUCUCCUCCUCC 20 13254

SCNNlA-9406 - UCAACGAAUUUCUCCUCCUCC 21 13255

SCNNlA-9407 - AUCAACGAAUUUCUCCUCCUCC 22 13256

SCNNlA-9408 - CAUCAACGAAUUUCUCCUCCUCC 23 13257

SCNNlA-9409 - CCAUCAACGAAUUUCUCCUCCUCC 24 13258

SCNNlA-9410 - UGCUGAGCCUCUAGCUCC 18 13259

SCNNlA-9411 - UUGCUGAGCCUCUAGCUCC 19 13260

SCNNlA-5594 - CUUGCUGAGCCUCUAGCUCC 20 9443

SCNNlA-9412 - ACUUGCUGAGCCUCUAGCUCC 21 13261

SCNNlA-9413 - CACUUGCUGAGCCUCUAGCUCC 22 13262

SCNNlA-9414 - CCACUUGCUGAGCCUCUAGCUCC 23 13263

SCNNlA-9415 - CCCACUUGCUGAGCCUCUAGCUCC 24 13264

SCNNlA-9416 - CGCAGGUCUGCUGGCUCC 18 13265

SCNNlA-9417 - CCGCAGGUCUGCUGGCUCC 19 13266

SCNNlA-5595 - CCCGCAGGUCUGCUGGCUCC 20 9444

SCNNlA-9418 - UCCCGCAGGUCUGCUGGCUCC 21 13267

SCNNlA-9419 - CUCCCGCAGGUCUGCUGGCUCC 22 13268

SCNNlA-9420 - ACUCCCGCAGGUCUGCUGGCUCC 23 13269

SCNNlA-9421 - AACUCCCGCAGGUCUGCUGGCUCC 24 13270

SCNNlA-9422 - CCUGGAGCCCUGCAGUCC 18 13271

SCNNlA-9423 - UCCUGGAGCCCUGCAGUCC 19 13272

SCNNlA-6114 - CUCCUGGAGCCCUGCAGUCC 20 9963

SCNNlA-9424 - CCUCCUGGAGCCCUGCAGUCC 21 13273

SCNNlA-9425 - ACCUCCUGGAGCCCUGCAGUCC 22 13274

SCNNlA-9426 - GACCUCCUGGAGCCCUGCAGUCC 23 13275

SCNNlA-9427 - AGACCUCCUGGAGCCCUGCAGUCC 24 13276

SCNNlA-9428 - A A A A AG A AC AG A A U G U C C 18 13277

SCNNlA-9429 - AAAAAAGAACAGAAUGUCC 19 13278

SCNNlA-9430 - UAAAAAAGAACAGAAUGUCC 20 13279

SCNNlA-9431 - GU AAAAAAGAACAGAAUGUCC 21 13280

SCNNlA-9432 - UGUAAAAAAGAACAGAAUGUCC 22 13281

SCNNlA-9433 - GUGUAAAAAAGAACAGAAUGUCC 23 13282

SCNNlA-9434 - AGUGUAAAAAAGAACAGAAUGUCC 24 13283

1445

5535.1 SCNNlA-9435 - AAUCCAGCUGUCCCUUCC 18 13284

SCNNlA-9436 - AAAUCCAGCUGUCCCUUCC 19 13285

SCNNlA-9437 - AAAAUCCAGCUGUCCCUUCC 20 13286

SCNNlA-9438 - AAAAAUCCAGCUGUCCCUUCC 21 13287

SCNNlA-9439 - GAAAAAUCCAGCUGUCCCUUCC 22 13288

SCNNlA-9440 - AGAAAAAUCCAGCUGUCCCUUCC 23 13289

SCNNlA-9441 - AAGAAAAAUCCAGCUGUCCCUUCC 24 13290

SCNNlA-9442 - CCCCCUUGCUCUCCUUCC 18 13291

SCNNlA-9443 - CCCCCCUUGCUCUCCUUCC 19 13292

SCNNlA-5598 - UCCCCCCUUGCUCUCCUUCC 20 9447

SCNNlA-9444 - CUCCCCCCUUGCUCUCCUUCC 21 13293

SCNNlA-9445 - ACUCCCCCCUUGCUCUCCUUCC 22 13294

SCNNlA-9446 - GACUCCCCCCUUGCUCUCCUUCC 23 13295

SCNNlA-9447 - GGACUCCCCCCUUGCUCUCCUUCC 24 13296

SCNNlA-1895 - UCAUGAAGGGGAACAAGC 18 5744

SCNNlA-1896 - CUCAUGAAGGGGAACAAGC 19 5745

SCNNlA-176 - GCUCAUGAAGGGGAACAAGC 20 811

SCNNlA-1897 - GGCUCAUGAAGGGGAACAAGC 21 5746

SCNNlA-1898 - GGGCUCAUGAAGGGGAACAAGC 22 5747

SCNNlA-1901 - GGGGCUCAUGAAGGGGAACAAGC 23 5750

SCNNlA-1902 - CGGGGCUCAUGAAGGGGAACAAGC 24 5751

SCNNlA-1903 - UCAUGGAGGGGAACAAGC 18 5752

SCNNlA-1904 - CUCAUGGAGGGGAACAAGC 19 5753

SCNNlA-5 - UCUCAUGGAGGGGAACAAGC 20 557

SCNNlA-1905 - GUCUCAUGGAGGGGAACAAGC 21 5754

SCNNlA-1906 - GGUCUCAUGGAGGGGAACAAGC 22 5755

SCNNlA-1907 - AGGUCUCAUGGAGGGGAACAAGC 23 5756

SCNNlA-1908 - CAGGUCUCAUGGAGGGGAACAAGC 24 5757

SCNNlA-9448 - AACCUGGGAGUGGGAAGC 18 13297

SCNNlA-9449 - CAACCUGGGAGUGGGAAGC 19 13298

SCNNlA-5228 - GCAACCUGGGAGUGGGAAGC 20 9077

SCNNlA-9450 - CGCAACCUGGGAGUGGGAAGC 21 13299

SCNNlA-9451 - CCGCAACCUGGGAGUGGGAAGC 22 13300

SCNNlA-9452 - GCCGCAACCUGGGAGUGGGAAGC 23 13301

SCNNlA-9453 - AGCCGCAACCUGGGAGUGGGAAGC 24 13302

SCNNlA-1909 - AGCAGUAUCAAGGUAAGC 18 5758

SCNNlA-1910 - GAGCAGUAUCAAGGUAAGC 19 5759

SCNNlA-1911 - UGAGCAGUAUCAAGGUAAGC 20 5760

SCNNlA-1912 - AUGAGCAGUAUCAAGGUAAGC 21 5761

SCNNlA-1913 - CAUGAGCAGUAUCAAGGUAAGC 22 5762

SCNNlA-1914 - UCAUGAGCAGUAUCAAGGUAAGC 23 5763

SCNNlA-1915 - AUCAUGAGCAGUAUCAAGGUAAGC 24 5764

1446

5535.1 SCNNlA-9454 - ACAG AAU CAGG ACACAG C 18 13303

SCNNlA-9455 - GACAGAAUCAGGACACAGC 19 13304

SCNNlA-9456 - AGACAGAAUCAGGACACAGC 20 13305

SCNNlA-9457 - GAGACAGAAUCAGGACACAGC 21 13306

SCNNlA-9458 - AGAGACAGAAUCAGGACACAGC 22 13307

SCNNlA-9459 - CAG AG ACAG AAU CAGG ACACAG C 23 13308

SCNNlA-9460 - GCAGAGACAGAAUCAGGACACAGC 24 13309

SCNNlA-9461 - CAACUCUGUGACCACAGC 18 13310

SCNNlA-9462 - GCAACUCUGUGACCACAGC 19 13311

SCNNlA-5599 - UGCAACUCUGUGACCACAGC 20 9448

SCNNlA-9463 - CUGCAACUCUGUGACCACAGC 21 13312

SCNNlA-9464 - CCUGCAACUCUGUGACCACAGC 22 13313

SCNNlA-9465 - UCCUGCAACUCUGUGACCACAGC 23 13314

SCNNlA-9466 - UUCCUGCAACUCUGUGACCACAGC 24 13315

SCNNlA-9467 - GGGUGGCGAGGAAUCAGC 18 13316

SCNNlA-9468 - GGGGUGGCGAGGAAUCAGC 19 13317

SCNNlA-5229 - GGGGGUGGCGAGGAAUCAGC 20 9078

SCNNlA-9469 - AGGGGGUGGCGAGGAAUCAGC 21 13318

SCNNlA-9470 - GAGGGGGUGGCGAGGAAUCAGC 22 13319

SCNNlA-9471 - GGAGGGGGUGGCGAGGAAUCAGC 23 13320

SCNNlA-9472 - UGGAGGGGGUGGCGAGGAAUCAGC 24

13321

SCNNlA-9473 - GGCCAGAAAGAGGAGAGC 18 13322

SCNNlA-9474 - AGGCCAGAAAGAGGAGAGC 19 13323

SCNNlA-6119 - CAGGCCAGAAAGAGGAGAGC 20 9968

SCNNlA-9475 - GCAGGCCAGAAAGAGGAGAGC 21 13324

SCNNlA-9476 - GGCAGGCCAGAAAGAGGAGAGC 22 13325

SCNNlA-9477 - AGGCAGGCCAGAAAGAGGAGAGC 23 13326

SCNNlA-9478 - GAGGCAGGCCAGAAAGAGGAGAGC 24 13327

SCNNlA-9479 - CCAGGUUGGACCCUGAGC 18 13328

SCNNlA-9480 - ACCAGGUUGGACCCUGAGC 19 13329

SCNNlA-9481 - GACCAGGUUGGACCCUGAGC 20 13330

SCNNlA-9482 - AGACCAGGUUGGACCCUGAGC 21 13331

SCNNlA-9483 - CAGACCAGGUUGGACCCUGAGC 22 13332

SCNNlA-9484 - ACAGACCAGGUUGGACCCUGAGC 23 13333

SCNNlA-9485 - CACAGACCAGGUUGGACCCUGAGC 24 13334

SCNNlA-9486 - UGCUCCCACUUAGUGAGC 18 13335

SCNNlA-9487 - CUGCUCCCACUUAGUGAGC 19 13336

SCNNlA-5230 - GCUGCUCCCACUUAGUGAGC 20 9079

SCNNlA-9488 - CGCUGCUCCCACUUAGUGAGC 21 13337

SCNNlA-9489 - GCGCUGCUCCCACUUAGUGAGC 22 13338

SCNNlA-9490 - UGCGCUGCUCCCACUUAGUGAGC 23 13339

1447

5535.1 SCNNlA-9491 - GUGCGCUGCUCCCACUUAGUGAGC 24 13340

SCNNlA-9492 - GUCGCAAGAGACUGCCGC 18 13341

SCNNlA-9493 - AGUCGCAAGAGACUGCCGC 19 13342

SCNNlA-9494 - AAGUCGCAAGAGACUGCCGC 20 13343

SCNNlA-9495 - GAAGUCGCAAGAGACUGCCGC 21 13344

SCNNlA-9496 - AGAAGUCGCAAGAGACUGCCGC 22 13345

SCNNlA-9497 - AAGAAGUCGCAAGAGACUGCCGC 23 13346

SCNNlA-9498 - UAAGAAGUCGCAAGAGACUGCCGC 24 13347

SCNNlA-9499 - UUCACUUUAAGAAGUCGC 18 13348

SCNNlA-9500 - UUUCACUUUAAGAAGUCGC 19 13349

SCNNlA-9501 - CUUUCACUUUAAGAAGUCGC 20 13350

SCNNlA-9502 - GCUUUCACUUUAAGAAGUCGC 21 13351

SCNNlA-9503 - GGCUUUCACUUUAAGAAGUCGC 22 13352

SCNNlA-9504 - CGGCUUUCACUUUAAGAAGUCGC 23 13353

SCNNlA-9505 - CCGGCUUUCACUUUAAGAAGUCGC 24 13354

SCNNlA-9506 - C U G G C A A A U AG A A A AG G C 18 13355

SCNNlA-9507 - GCUGGCAAAUAGAAAAGGC 19 13356

SCNNlA-6121 - AG C U G G C A A A U AG A A A AG G C 20 9970

SCNNlA-9508 - GAGCUGGCAAAUAGAAAAGGC 21 13357

SCNNlA-9509 - UGAGCUGGCAAAUAGAAAAGGC 22 13358

SCNNlA-9510 - AUGAGCUGGCAAAUAGAAAAGGC 23 13359

SCNNlA-9511 - CAUGAGCUGGCAAAUAGAAAAGGC 24 13360

SCNNlA-9512 - AGUGAGAGGGGGCAAGGC 18 13361

SCNNlA-9513 - GAGUGAGAGGGGGCAAGGC 19 13362

SCNNlA-9514 - AGAGUGAGAGGGGGCAAGGC 20 13363

SCNNlA-9515 - UAGAGUGAGAGGGGGCAAGGC 21 13364

SCNNlA-9516 - CUAGAGUGAGAGGGGGCAAGGC 22 13365

SCNNlA-9517 - CCUAGAGUGAGAGGGGGCAAGGC 23 13366

SCNNlA-9518 - GCCUAGAGUGAGAGGGGGCAAGGC 24 13367

SCNNlA-9519 - UAGAGAGAGGAGGCAGGC 18 13368

SCNNlA-9520 - UUAGAGAGAGGAGGCAGGC 19 13369

SCNNlA-9521 - AUUAGAGAGAGGAGGCAGGC 20 13370

SCNNlA-9522 - GAUUAGAGAGAGGAGGCAGGC 21 13371

SCNNlA-9523 - GGAUUAGAGAGAGGAGGCAGGC 22 13372

SCNNlA-9524 - AGGAUUAGAGAGAGGAGGCAGGC 23 13373

SCNNlA-9525 - CAGGAUUAGAGAGAGGAGGCAGGC 24 13374

SCNNlA-9526 - AGUGGUUGGAUUUCAGGC 18 13375

SCNNlA-9527 - UAGUGGUUGGAUUUCAGGC 19 13376

SCNNlA-9528 - CUAGUGGUUGGAUUUCAGGC 20 13377

SCNNlA-9529 - GCUAGUGGUUGGAUUUCAGGC 21 13378

SCNNlA-9530 - AGCUAGUGGUUGGAUUUCAGGC 22 13379

SCNNlA-9531 - AAGCUAGUGGUUGGAUUUCAGGC 23 13380

1448

5535.1 SCNNlA-9532 - UAAGCUAGUGGUUGGAUUUCAGGC 24

13381

SCNNlA-9533 - GAGGUCAGGGCCAGAGGC 18 13382

SCNNlA-9534 - CGAGGUCAGGGCCAGAGGC 19 13383

SCNNlA-5607 - UCGAGGUCAGGGCCAGAGGC 20 9456

SCNNlA-9535 - CUCGAGGUCAGGGCCAGAGGC 21 13384

SCNNlA-9536 - GCUCGAGGUCAGGGCCAGAGGC 22 13385

SCNNlA-9537 - AGCUCGAGGUCAGGGCCAGAGGC 23 13386

SCNNlA-9538 - CAGCUCGAGGUCAGGGCCAGAGGC 24 13387

SCNNlA-9539 - AGAGAGGGAGUGAGAGGC 18 13388

SCNNlA-9540 - UAGAGAGGGAGUGAGAGGC 19 13389

SCNNlA-6123 - AUAGAGAGGGAGUGAGAGGC 20 9972

SCNNlA-9541 - GAUAGAGAGGGAGUGAGAGGC 21 13390

SCNNlA-9542 - AGAUAGAGAGGGAGUGAGAGGC 22 13391

SCNNlA-9543 - CAGAUAGAGAGGGAGUGAGAGGC 23 13392

SCNNlA-9544 - GCAGAUAGAGAGGGAGUGAGAGGC 24 13393

SCNNlA-9545 - CUCUCUUCUCUGCAGGGC 18 13394

SCNNlA-9546 - UCUCUCUUCUCUGCAGGGC 19 13395

SCNNlA-9547 - UUCUCUCUUCUCUGCAGGGC 20 13396

SCNNlA-9548 - CUUCUCUCUUCUCUGCAGGGC 21 13397

SCNNlA-9549 - UCUUCUCUCUUCUCUGCAGGGC 22 13398

SCNNlA-9550 - CUCUUCUCUCUUCUCUGCAGGGC 23 13399

SCNNlA-9551 - CCUCUUCUCUCUUCUCUGCAGGGC 24 13400

SCNNlA-9552 - ACAGCUCGAGGUCAGGGC 18 13401

SCNNlA-9553 - CACAGCUCGAGGUCAGGGC 19 13402

SCNNlA-9554 - ACACAGCUCGAGGUCAGGGC 20 13403

SCNNlA-9555 - GACACAGCUCGAGGUCAGGGC 21 13404

SCNNlA-9556 - GGACACAGCUCGAGGUCAGGGC 22 13405

SCNNlA-9557 - AGGACACAGCUCGAGGUCAGGGC 23 13406

SCNNlA-9558 - CAGGACACAGCUCGAGGUCAGGGC 24 13407

SCNNlA-1928 - GUGGGACAUGGGCAUGGC 18 5777

SCNNlA-1929 - GGUGGGACAUGGGCAUGGC 19 5778

SCNNlA-1930 - GGGUGGGACAUGGGCAUGGC 20 5779

SCNNlA-1931 - AGGGUGGGACAUGGGCAUGGC 21 5780

SCNNlA-1932 - CAGGGUGGGACAUGGGCAUGGC 22 5781

SCNNlA-1933 - GCAGGGUGGGACAUGGGCAUGGC 23 5782

SCNNlA-1934 - CGCAGGGUGGGACAUGGGCAUGGC 24 5783

SCNNlA-9559 - AAGGUUGGAGGGGGUGGC 18 13408

SCNNlA-9560 - CAAGGUUGGAGGGGGUGGC 19 13409

SCNNlA-9561 - ACAAGGUUGGAGGGGGUGGC 20 13410

SCNNlA-9562 - GACAAGGUUGGAGGGGGUGGC 21 13411

SCNNlA-9563 - GGACAAGGUUGGAGGGGGUGGC 22 13412

1449

5535.1 SCNNlA-9564 - UGGACAAGGUUGGAGGGGGUGGC 23 13413

SCNNlA-9565 - CUGGACAAGGUUGGAGGGGGUGGC 24

13414

SCNNlA-9566 - AGACAGAAAGGGAGGUGC 18 13415

SCNNlA-9567 - GAGACAGAAAGGGAGGUGC 19 13416

SCNNlA-9568 - AGAGACAGAAAGGGAGGUGC 20 13417

SCNNlA-9569 - CAGAGACAGAAAGGGAGGUGC 21 13418

SCNNlA-9570 - GCAGAGACAGAAAGGGAGGUGC 22 13419

SCNNlA-9571 - GGCAGAGACAGAAAGGGAGGUGC 23 13420

SCNNlA-9572 - GGGCAGAGACAGAAAGGGAGGUGC 24 13421

SCNNlA-9573 - UGCUGAGCACCUUAUUGC 18 13422

SCNNlA-9574 - GUGCUGAGCACCUUAUUGC 19 13423

SCNNlA-5237 - GGUGCUGAGCACCUUAUUGC 20 9086

SCNNlA-9575 - GGGUGCUGAGCACCUUAUUGC 21 13424

SCNNlA-9576 - AGGGUGCUGAGCACCUUAUUGC 22 13425

SCNNlA-9577 - CAGGGUGCUGAGCACCUUAUUGC 23 13426

SCNNlA-9578 - CCAGGGUGCUGAGCACCUUAUUGC 24 13427

SCNNlA-9579 - GGAGCUGAGACACAGAUC 18 13428

SCNNlA-9580 - AGGAGCUGAGACACAGAUC 19 13429

SCNNlA-9581 - CAGGAGCUGAGACACAGAUC 20 13430

SCNNlA-9582 - GCAGGAGCUGAGACACAGAUC 21 13431

SCNNlA-9583 - GGCAGGAGCUGAGACACAGAUC 22 13432

SCNNlA-9584 - AGGCAGGAGCUGAGACACAGAUC 23 13433

SCNNlA-9585 - GAGGCAGGAGCUGAGACACAGAUC 24 13434

SCNNlA-9586 - UCGAAAGGUGGCCCUAUC 18 13435

SCNNlA-9587 - CUCGAAAGGUGGCCCUAUC 19 13436

SCNNlA-5626 - ACUCGAAAGGUGGCCCUAUC 20 9475

SCNNlA-9588 - AACUCGAAAGGUGGCCCUAUC 21 13437

SCNNlA-9589 - AAACUCGAAAGGUGGCCCUAUC 22 13438

SCNNlA-9590 - AAAACUCGAAAGGUGGCCCUAUC 23 13439

SCNNlA-9591 - CAAAACUCGAAAGGUGGCCCUAUC 24 13440

SCNNlA-1935 - CUUCCAAGGGGAGGUAUC 18 5784

SCNNlA-1936 - CCUUCCAAGGGGAGGUAUC 19 5785

SCNNlA-1937 - CCCUUCCAAGGGGAGGUAUC 20 5786

SCNNlA-1938 - UCCCUUCCAAGGGGAGGUAUC 21 5787

SCNNlA-1939 - GUCCCUUCCAAGGGGAGGUAUC 22 5788

SCNNlA-1940 - UGUCCCUUCCAAGGGGAGGUAUC 23 5789

SCNNlA-1941 - CUGUCCCUUCCAAGGGGAGGUAUC 24 5790

SCNNlA-1942 - GCUCUCCCCAAUCCACUC 18 5791

SCNNlA-1943 - UGCUCUCCCCAAUCCACUC 19 5792

SCNNlA-410 - UUGCUCUCCCCAAUCCACUC 20 4259

SCNNlA-1944 - CUUGCUCUCCCCAAUCCACUC 21 5793

1450

5535.1 SCNNlA-1945 - CCUUGCUCUCCCCAAUCCACUC 22 5794

SCNNlA-1946 - CCCUUGCUCUCCCCAAUCCACUC 23 5795

SCNNlA-1947 - ACCCUUGCUCUCCCCAAUCCACUC 24 5796

SCNNlA-1948 - GCCCUCCACAGUCCACUC 18 5797

SCNNlA-1949 - AGCCCUCCACAGUCCACUC 19 5798

SCNNlA-170 - UAGCCCUCCACAGUCCACUC 20 808

SCNNlA-1950 - CUAGCCCUCCACAGUCCACUC 21 5799

SCNNlA-1951 - UCUAGCCCUCCACAGUCCACUC 22 5800

SCNNlA-1952 - CUCUAGCCCUCCACAGUCCACUC 23 5801

SCNNlA-1953 - ACUCUAGCCCUCCACAGUCCACUC 24 5802

SCNNlA-9592 - GGAGGCAGCCCAGACCUC 18 13441

SCNNlA-9593 - UGGAGGCAGCCCAGACCUC 19 13442

SCNNlA-9594 - CUGGAGGCAGCCCAGACCUC 20 13443

SCNNlA-9595 - GCUGGAGGCAGCCCAGACCUC 21 13444

SCNNlA-9596 - AGCUGGAGGCAGCCCAGACCUC 22 13445

SCNNlA-9597 - AAGCUGGAGGCAGCCCAGACCUC 23 13446

SCNNlA-9598 - GAAGCUGGAGGCAGCCCAGACCUC 24 13447

SCNNlA-9599 - CCCAGUUCACCUGCCCUC 18 13448

SCNNlA-9600 - UCCCAGUUCACCUGCCCUC 19 13449

SCNNlA-6132 - CUCCCAGUUCACCUGCCCUC 20 9981

SCNNlA-9601 - ACUCCCAGUUCACCUGCCCUC 21 13450

SCNNlA-9602 - UACUCCCAGUUCACCUGCCCUC 22 13451

SCNNlA-9603 - GUACUCCCAGUUCACCUGCCCUC 23 13452

SCNNlA-9604 - AGUACUCCCAGUUCACCUGCCCUC 24 13453

SCNNlA-9605 - UUGCUGAGCCUCUAGCUC 18 13454

SCNNlA-9606 - CUUGCUGAGCCUCUAGCUC 19 13455

SCNNlA-9607 - ACUUGCUGAGCCUCUAGCUC 20 13456

SCNNlA-9608 - CACUUGCUGAGCCUCUAGCUC 21 13457

SCNNlA-9609 - CCACUUGCUGAGCCUCUAGCUC 22 13458

SCNNlA-9610 - CCCACUUGCUGAGCCUCUAGCUC 23 13459

SCNNlA-9611 - GCCCACUUGCUGAGCCUCUAGCUC 24 13460

SCNNlA-1960 - CAAUCCACUCCGGGGCUC 18 5809

SCNNlA-1961 - CCAAUCCACUCCGGGGCUC 19 5810

SCNNlA-1962 - CCCAAUCCACUCCGGGGCUC 20 5811

SCNNlA-1963 - CCCCAAUCCACUCCGGGGCUC 21 5812

SCNNlA-1964 - UCCCCAAUCCACUCCGGGGCUC 22 5813

SCNNlA-1965 - CUCCCCAAUCCACUCCGGGGCUC 23 5814

SCNNlA-1966 - UCUCCCCAAUCCACUCCGGGGCUC 24 5815

SCNNlA-9612 - AAUGUAAGGACCUGGCUC 18 13461

SCNNlA-9613 - CAAUGUAAGGACCUGGCUC 19 13462

SCNNlA-9614 - CCAAUGUAAGGACCUGGCUC 20 13463

SCNNlA-9615 - CCCAAUGUAAGGACCUGGCUC 21 13464

1451

5535.1 SCNNlA-9616 - GCCCAAUGUAAGGACCUGGCUC 22 13465

SCNNlA-9617 - UGCCCAAUGUAAGGACCUGGCUC 23 13466

SCNNlA-9618 - AUGCCCAAUGUAAGGACCUGGCUC 24 13467

SCNNlA-9619 - CCGCAGGUCUGCUGGCUC 18 13468

SCNNlA-9620 - CCCGCAGGUCUGCUGGCUC 19 13469

SCNNlA-9621 - UCCCGCAGGUCUGCUGGCUC 20 13470

SCNNlA-9622 - CUCCCGCAGGUCUGCUGGCUC 21 13471

SCNNlA-9623 - ACUCCCGCAGGUCUGCUGGCUC 22 13472

SCNNlA-9624 - AACUCCCGCAGGUCUGCUGGCUC 23 13473

SCNNlA-9625 - CAACUCCCGCAGGUCUGCUGGCUC 24 13474

SCNNlA-1967 - CAGCCCAUACCAGGUCUC 18 5816

SCNNlA-1968 - GCAGCCCAUACCAGGUCUC 19 5817

SCNNlA-159 - UGCAGCCCAUACCAGGUCUC 20 803

SCNNlA-1969 - CUGCAGCCCAUACCAGGUCUC 21 5818

SCNNlA-1970 - UCUGCAGCCCAUACCAGGUCUC 22 5819

SCNNlA-1971 - CUCUGCAGCCCAUACCAGGUCUC 23 5820

SCNNlA-1972 - CCUCUGCAGCCCAUACCAGGUCUC 24 5821

SCNNlA-9626 - CCCCCAUGAGUCUGUCUC 18 13475

SCNNlA-9627 - UCCCCCAUGAGUCUGUCUC 19 13476

SCNNlA-5636 - AUCCCCCAUGAGUCUGUCUC 20 9485

SCNNlA-9628 - GAUCCCCCAUGAGUCUGUCUC 21 13477

SCNNlA-9629 - CGAUCCCCCAUGAGUCUGUCUC 22 13478

SCNNlA-9630 - CCGAUCCCCCAUGAGUCUGUCUC 23 13479

SCNNlA-9631 - CCCGAUCCCCCAUGAGUCUGUCUC 24 13480

SCNNlA-9632 - CAGAGAUGACACCUUCUC 18 13481

SCNNlA-9633 - GCAGAGAUGACACCUUCUC 19 13482

SCNNlA-5637 - AGCAGAGAUGACACCUUCUC 20 9486

SCNNlA-9634 - CAGCAGAGAUGACACCUUCUC 21 13483

SCNNlA-9635 - UCAGCAGAGAUGACACCUUCUC 22 13484

SCNNlA-9636 - UUCAGCAGAGAUGACACCUUCUC 23 13485

SCNNlA-9637 - AUUCAGCAGAGAUGACACCUUCUC 24 13486

SCNNlA-9638 - UCCUGGAGCCCUGCAGUC 18 13487

SCNNlA-9639 - CUCCUGGAGCCCUGCAGUC 19 13488

SCNNlA-9640 - CCUCCUGGAGCCCUGCAGUC 20 13489

SCNNlA-9641 - ACCUCCUGGAGCCCUGCAGUC 21 13490

SCNNlA-9642 - GACCUCCUGGAGCCCUGCAGUC 22 13491

SCNNlA-9643 - AGACCUCCUGGAGCCCUGCAGUC 23 13492

SCNNlA-9644 - CAGACCUCCUGGAGCCCUGCAGUC 24 13493

SCNNlA-9645 - CCCCCCUUGCUCUCCUUC 18 13494

SCNNlA-9646 - UCCCCCCUUGCUCUCCUUC 19 13495

SCNNlA-9647 - CUCCCCCCUUGCUCUCCUUC 20 13496

SCNNlA-9648 - ACUCCCCCCUUGCUCUCCUUC 21 13497

1452

5535.1 SCNNlA-9649 - GACUCCCCCCUUGCUCUCCUUC 22 13498

SCNNlA-9650 - GGACUCCCCCCUUGCUCUCCUUC 23 13499

SCNNlA-9651 - GGGACUCCCCCCUUGCUCUCCUUC 24 13500

SCNNlA-9652 - UGCUUUCCCUGCCUCUUC 18 13501

SCNNlA-9653 - CUGCUUUCCCUGCCUCUUC 19 13502

SCNNlA-9654 - CCUGCUUUCCCUGCCUCUUC 20 13503

SCNNlA-9655 - GCCUGCUUUCCCUGCCUCUUC 21 13504

SCNNlA-9656 - UGCCUGCUUUCCCUGCCUCUUC 22 13505

SCNNlA-9657 - GUGCCUGCUUUCCCUGCCUCUUC 23 13506

SCNNlA-9658 - AGUGCCUGCUUUCCCUGCCUCUUC 24 13507

SCNNlA-9659 - GCAGAGGAGAGGCCGUUC 18 13508

SCNNlA-9660 - AGCAGAGGAGAGGCCGUUC 19 13509

SCNNlA-9661 - AAGCAGAGGAGAGGCCGUUC 20 13510

SCNNlA-9662 - GAAGCAGAGGAGAGGCCGUUC 21 13511

SCNNlA-9663 - GGAAGCAGAGGAGAGGCCGUUC 22 13512

SCNNlA-9664 - GGGAAGCAGAGGAGAGGCCGUUC 23 13513

SCNNlA-9665 - AGGGAAGCAGAGGAGAGGCCGUUC 24 13514

SCNNlA-1973 - GCAGCCUCACUCGGGUUC 18 5822

SCNNlA-1974 - GGCAGCCUCACUCGGGUUC 19 5823

SCNNlA-1975 - GGGCAGCCUCACUCGGGUUC 20 5824

SCNNlA-1976 - GGGGCAGCCUCACUCGGGUUC 21 5825

SCNNlA-1977 - AGGGGCAGCCUCACUCGGGUUC 22 5826

SCNNlA-1978 - CAGGGGCAGCCUCACUCGGGUUC 23 5827

SCNNlA-1979 - CCAGGGGCAGCCUCACUCGGGUUC 24 5828

SCNNlA-9666 - AAGGGAGACUGGAGUUUC 18 13515

SCNNlA-9667 - CAAGGGAGACUGGAGUUUC 19 13516

SCNNlA-9668 - UCAAGGGAGACUGGAGUUUC 20 13517

SCNNlA-9669 - CUCAAGGGAGACUGGAGUUUC 21 13518

SCNNlA-9670 - GCUCAAGGGAGACUGGAGUUUC 22 13519

SCNNlA-9671 - GGCUCAAGGGAGACUGGAGUUUC 23 13520

SCNNlA-9672 - UGGCUCAAGGGAGACUGGAGUUUC 24 13521

SCNNlA-9673 - AGGAGGCAGGCCAGAAAG 18 13522

SCNNlA-9674 - GAGGAGGCAGGCCAGAAAG 19 13523

SCNNlA-6139 - AGAGGAGGCAGGCCAGAAAG 20 9988

SCNNlA-9675 - GAGAGGAGGCAGGCCAGAAAG 21 13524

SCNNlA-9676 - AGAGAGGAGGCAGGCCAGAAAG 22 13525

SCNNlA-9677 - GAGAGAGGAGGCAGGCCAGAAAG 23 13526

SCNNlA-9678 - AGAGAGAGGAGGCAGGCCAGAAAG 24 13527

SCNNlA-9679 - CUGCUGGCUCCAGGAAAG 18 13528

SCNNlA-9680 - UCUGCUGGCUCCAGGAAAG 19 13529

SCNNlA-9681 - GUCUGCUGGCUCCAGGAAAG 20 13530

SCNNlA-9682 - GGUCUGCUGGCUCCAGGAAAG 21 13531

1453

5535.1 SCNNlA-9683 - AGGUCUGCUGGCUCCAGGAAAG 22 13532

SCNNlA-9684 - CAGGUCUGCUGGCUCCAGGAAAG 23 13533

SCNNlA-9685 - GCAGGUCUGCUGGCUCCAGGAAAG 24 13534

SCNNlA-9686 - G AG G A A U C AG C AG G A A AG 18 13535

SCNNlA-9687 - CGAGGAAUCAGCAGGAAAG 19 13536

SCNNlA-5244 - GCGAGGAAUCAGCAGGAAAG 20 9093

SCNNlA-9688 - GGCGAGGAAUCAGCAGGAAAG 21 13537

SCNNlA-9689 - UGGCGAGGAAUCAGCAGGAAAG 22 13538

SCNNlA-9690 - GUGGCGAGGAAUCAGCAGGAAAG 23 13539

SCNNlA-9691 - GGUGGCGAGGAAUCAGCAGGAAAG 24 13540

SCNNlA-1980 - CUCAUGAAGGGGAACAAG 18 5829

SCNNlA-1981 - GCUCAUGAAGGGGAACAAG 19 5830

SCNNlA-1982 - GGCUCAUGAAGGGGAACAAG 20 5831

SCNNlA-1983 - GGGCUCAUGAAGGGGAACAAG 21 5832

SCNNlA-1984 - GGGGCUCAUGAAGGGGAACAAG 22 5833

SCNNlA-1985 - CGGGGCUCAUGAAGGGGAACAAG 23 5834

SCNNlA-1986 - CCGGGGCUCAUGAAGGGGAACAAG 24 5835

SCNNlA-1987 - CUCAUGGAGGGGAACAAG 18 5836

SCNNlA-1988 - UCUCAUGGAGGGGAACAAG 19 5837

SCNNlA-165 - GUCUCAUGGAGGGGAACAAG 20 805

SCNNlA-1989 - GGUCUCAUGGAGGGGAACAAG 21 5838

SCNNlA-1990 - AGGUCUCAUGGAGGGGAACAAG 22 5839

SCNNlA-1991 - CAGGUCUCAUGGAGGGGAACAAG 23 5840

SCNNlA-1992 - CCAGGUCUCAUGGAGGGGAACAAG 24 5841

SCNNlA-1993 - CCAGCUGUCCCUUCCAAG 18 5842

SCNNlA-1994 - UCCAGCUGUCCCUUCCAAG 19 5843

SCNNlA-412 - AUCCAGCUGUCCCUUCCAAG 20 4261

SCNNlA-9692 - AAUCCAGCUGUCCCUUCCAAG 21 13541

SCNNlA-9693 - AAAUCCAGCUGUCCCUUCCAAG 22 13542

SCNNlA-9694 - AAAAUCCAGCUGUCCCUUCCAAG 23 13543

SCNNlA-9695 - AAAAAUCCAGCUGUCCCUUCCAAG 24 13544

SCNNlA-9696 - GAGAGGGGGCAAGGCAAG 18 13545

SCNNlA-9697 - UGAGAGGGGGCAAGGCAAG 19 13546

SCNNlA-5246 - GUGAGAGGGGGCAAGGCAAG 20 9095

SCNNlA-9698 - AGUGAGAGGGGGCAAGGCAAG 21 13547

SCNNlA-9699 - GAGUGAGAGGGGGCAAGGCAAG 22 13548

SCNNlA-9700 - AGAGUGAGAGGGGGCAAGGCAAG 23 13549

SCNNlA-9701 - UAGAGUGAGAGGGGGCAAGGCAAG 24 13550

SCNNlA-9702 - GUGGCCCUAUCAGGGAAG 18 13551

SCNNlA-9703 - GGUGGCCCUAUCAGGGAAG 19 13552

SCNNlA-9704 - AGGUGGCCCUAUCAGGGAAG 20 13553

SCNNlA-9705 - AAGGUGGCCCUAUCAGGGAAG 21 13554

1454

5535.1 SCNNlA-9706 - AAAGGUGGCCCUAUCAGGGAAG 22 13555

SCNNlA-9707 - GAAAGGUGGCCCUAUCAGGGAAG 23 13556

SCNNlA-9708 - CGAAAGGUGGCCCUAUCAGGGAAG 24 13557

SCNNlA-9709 - CAACCUGGGAGUGGGAAG 18 13558

SCNNlA-9710 - GCAACCUGGGAGUGGGAAG 19 13559

SCNNlA-9711 - CGCAACCUGGGAGUGGGAAG 20 13560

SCNNlA-9712 - CCGCAACCUGGGAGUGGGAAG 21 13561

SCNNlA-9713 - GCCGCAACCUGGGAGUGGGAAG 22 13562

SCNNlA-9714 - AGCCGCAACCUGGGAGUGGGAAG 23 13563

SCNNlA-9715 - CAGCCGCAACCUGGGAGUGGGAAG 24 13564

SCNNlA-2001 - ACUCCGGGGCUCAUGAAG 18 5850

SCNNlA-2002 - CACUCCGGGGCUCAUGAAG 19 5851

SCNNlA-453 - CCACUCCGGGGCUCAUGAAG 20 4302

SCNNlA-2003 - UCCACUCCGGGGCUCAUGAAG 21 5852

SCNNlA-2004 - AUCCACUCCGGGGCUCAUGAAG 22 5853

SCNNlA-2005 - AAUCCACUCCGGGGCUCAUGAAG 23 5854

SCNNlA-2006 - CAAUCCACUCCGGGGCUCAUGAAG 24 5855

SCNNlA-9716 - GCAACUCUGUGACCACAG 18 13565

SCNNlA-9717 - UGCAACUCUGUGACCACAG 19 13566

SCNNlA-9718 - CUGCAACUCUGUGACCACAG 20 13567

SCNNlA-9719 - CCUGCAACUCUGUGACCACAG 21 13568

SCNNlA-9720 - UCCUGCAACUCUGUGACCACAG 22 13569

SCNNlA-9721 - UUCCUGCAACUCUGUGACCACAG 23 13570

SCNNlA-9722 - AUUCCUGCAACUCUGUGACCACAG 24 13571

SCNNlA-9723 - GGAAAGAGGAGGGACCAG 18 13572

SCNNlA-9724 - AGGAAAGAGGAGGGACCAG 19 13573

SCNNlA-9725 - CAGGAAAGAGGAGGGACCAG 20 13574

SCNNlA-9726 - GCAGGAAAGAGGAGGGACCAG 21 13575

SCNNlA-9727 - AGCAGGAAAGAGGAGGGACCAG 22 13576

SCNNlA-9728 - CAGCAGGAAAGAGGAGGGACCAG 23 13577

SCNNlA-9729 - UCAGCAGGAAAGAGGAGGGACCAG 24 13578

SCNNlA-9730 - CUAAGUAGAUAGCCCCAG 18 13579

SCNNlA-9731 - GCUAAGUAGAUAGCCCCAG 19 13580

SCNNlA-5646 - CGCUAAGUAGAUAGCCCCAG 20 9495

SCNNlA-9732 - GCGCUAAGUAGAUAGCCCCAG 21 13581

SCNNlA-9733 - AGCGCUAAGUAGAUAGCCCCAG 22 13582

SCNNlA-9734 - AAGCGCUAAGUAGAUAGCCCCAG 23 13583

SCNNlA-9735 - AAAGCGCUAAGUAGAUAGCCCCAG 24 13584

SCNNlA-9736 - GCCCUAUCAGGGAAGCAG 18 13585

SCNNlA-9737 - GGCCCUAUCAGGGAAGCAG 19 13586

SCNNlA-5649 - UGGCCCUAUCAGGGAAGCAG 20 9498

SCNNlA-9738 - GUGGCCCUAUCAGGGAAGCAG 21 13587

1455

5535.1 SCNNlA-9739 - GGUGGCCCUAUCAGGGAAGCAG 22 13588

SCNNlA-9740 - AGGUGGCCCUAUCAGGGAAGCAG 23 13589

SCNNlA-9741 - AAGGUGGCCCUAUCAGGGAAGCAG 24 13590

SCNNlA-9742 - CCAGAAAGAGGAGAGCAG 18 13591

SCNNlA-9743 - G CCAG AAAG AGG AG AG CAG 19 13592

SCNNlA-9744 - GG CCAGAAAGAGGAGAGCAG 20 13593

SCNNlA-9745 - AGGCCAGAAAGAGGAGAGCAG 21 13594

SCNNlA-9746 - CAGGCCAGAAAGAGGAGAGCAG 22 13595

SCNNlA-9747 - GCAGGCCAGAAAGAGGAGAGCAG 23 13596

SCNNlA-9748 - GGCAGGCCAGAAAGAGGAGAGCAG 24 13597

SCNNlA-9749 - CUGGGAUAUGUGGGGCAG 18 13598

SCNNlA-9750 - UCUGGGAUAUGUGGGGCAG 19 13599

SCNNlA-5651 - CUCUGGGAUAUGUGGGGCAG 20 9500

SCNNlA-9751 - UCUCUGGGAUAUGUGGGGCAG 21 13600

SCNNlA-9752 - GUCUCUGGGAUAUGUGGGGCAG 22 13601

SCNNlA-9753 - GGUCUCUGGGAUAUGUGGGGCAG 23 13602

SCNNlA-9754 - GGGUCUCUGGGAUAUGUGGGGCAG 24

13603

SCNNlA-9755 - GGGGUGGCGAGGAAUCAG 18 13604

SCNNlA-9756 - GGGGGUGGCGAGGAAUCAG 19 13605

SCNNlA-9757 - AGGGGGUGGCGAGGAAUCAG 20 13606

SCNNlA-9758 - GAGGGGGUGGCGAGGAAUCAG 21 13607

SCNNlA-9759 - GGAGGGGGUGGCGAGGAAUCAG 22 13608

SCNNlA-9760 - UGGAGGGGGUGGCGAGGAAUCAG 23 13609

SCNNlA-9761 - UUGGAGGGGGUGGCGAGGAAUCAG 24

13610

SCNNlA-9762 - GGCCGCUGCACCUGUCAG 18 13611

SCNNlA-9763 - AGGCCGCUGCACCUGUCAG 19 13612

SCNNlA-9764 - CAGGCCGCUGCACCUGUCAG 20 13613

SCNNlA-9765 - CCAGGCCGCUGCACCUGUCAG 21 13614

SCNNlA-9766 - GCCAGGCCGCUGCACCUGUCAG 22 13615

SCNNlA-9767 - AGCCAGGCCGCUGCACCUGUCAG 23 13616

SCNNlA-9768 - CAGCCAGGCCGCUGCACCUGUCAG 24 13617

SCNNlA-9769 - UUGCUUGUCAAGAUUCAG 18 13618

SCNNlA-9770 - CUUGCUUGUCAAGAUUCAG 19 13619

SCNNlA-9771 - CCUUGCUUGUCAAGAUUCAG 20 13620

SCNNlA-9772 - UCCUUGCUUGUCAAGAUUCAG 21 13621

SCNNlA-9773 - CUCCUUGCUUGUCAAGAUUCAG 22 13622

SCNNlA-9774 - ACUCCUUGCUUGUCAAGAUUCAG 23 13623

SCNNlA-9775 - AACUCCUUGCUUGUCAAGAUUCAG 24 13624

SCNNlA-9776 - GAGGCAGGCCAGAAAGAG 18 13625

SCNNlA-9777 - GGAGGCAGGCCAGAAAGAG 19 13626

1456

5535.1 SCNNlA-9778 - AGGAGGCAGGCCAGAAAGAG 20 13627

SCNNlA-9779 - GAGGAGGCAGGCCAGAAAGAG 21 13628

SCNNlA-9780 - AGAGGAGGCAGGCCAGAAAGAG 22 13629

SCNNlA-9781 - GAGAGGAGGCAGGCCAGAAAGAG 23 13630

SCNNlA-9782 - AGAGAGGAGGCAGGCCAGAAAGAG 24 13631

SCNNlA-9783 - GGAAUCAGCAGGAAAGAG 18 13632

SCNNlA-9784 - AGGAAUCAGCAGGAAAGAG 19 13633

SCNNlA-9785 - GAGGAAUCAGCAGGAAAGAG 20 13634

SCNNlA-9786 - CGAGGAAUCAGCAGGAAAGAG 21 13635

SCNNlA-9787 - GCGAGGAAUCAGCAGGAAAGAG 22 13636

SCNNlA-9788 - GGCGAGGAAUCAGCAGGAAAGAG 23 13637

SCNNlA-9789 - UGGCGAGGAAUCAGCAGGAAAGAG 24 13638

SCNNlA-9790 - AAGAGACUGCCGCAAGAG 18 13639

SCNNlA-9791 - CAAGAGACUGCCGCAAGAG 19 13640

SCNNlA-5249 - GCAAGAGACUGCCGCAAGAG 20 9098

SCNNlA-9792 - CGCAAGAGACUGCCGCAAGAG 21 13641

SCNNlA-9793 - U CGCAAG AG ACUG CCG CAAG AG 22 13642

SCNNlA-9794 - G U CGCAAG AG ACUG CCG CAAG AG 23 13643

SCNNlA-9795 - AGUCGCAAGAGACUGCCGCAAGAG 24 13644

SCNNlA-9796 - AAGUAGAUAGCCCCAGAG 18 13645

SCNNlA-9797 - UAAGUAGAUAGCCCCAGAG 19 13646

SCNNlA-9798 - CUAAGUAGAUAGCCCCAGAG 20 13647

SCNNlA-9799 - GCUAAGUAGAUAGCCCCAGAG 21 13648

SCNNlA-9800 - CGCU AAGUAGAUAGCCCCAGAG 22 13649

SCNNlA-9801 - GCGCUAAGUAGAUAGCCCCAGAG 23 13650

SCNNlA-9802 - AGCGCUAAGUAGAUAGCCCCAGAG 24 13651

SCNNlA-9803 - CCUAUCAGGGAAGCAGAG 18 13652

SCNNlA-9804 - CCCUAUCAGGGAAGCAGAG 19 13653

SCNNlA-9805 - GCCCUAUCAGGGAAGCAGAG 20 13654

SCNNlA-9806 - GGCCCUAUCAGGGAAGCAGAG 21 13655

SCNNlA-9807 - UGGCCCUAUCAGGGAAGCAGAG 22 13656

SCNNlA-9808 - GUGGCCCUAUCAGGGAAGCAGAG 23 13657

SCNNlA-9809 - GGUGGCCCUAUCAGGGAAGCAGAG 24 13658

SCNNlA-9810 - AGAGGCAGGAUUAGAGAG 18 13659

SCNNlA-9811 - GAGAGGCAGGAUUAGAGAG 19 13660

SCNNlA-6147 - AGAGAGGCAGGAUUAGAGAG 20 9996

SCNNlA-9812 - AAGAGAGGCAGGAUUAGAGAG 21 13661

SCNNlA-9813 - GAAG AGAGGCAGGAUUAGAGAG 22 13662

SCNNlA-9814 - GGAAGAGAGGCAGGAUUAGAGAG 23 13663

SCNNlA-9815 - AGGAAGAGAGGCAGGAUUAGAGAG 24 13664

SCNNlA-9816 - AGGCCAGAAAGAGGAGAG 18 13665

SCNNlA-9817 - CAGGCCAGAAAGAGGAGAG 19 13666

1457

5535.1 SCNNlA-9818 - GCAGGCCAGAAAGAGGAGAG 20 13667

SCNNlA-9819 - GGCAGGCCAGAAAGAGGAGAG 21 13668

SCNNlA-9820 - AGGCAGGCCAGAAAGAGGAGAG 22 13669

SCNNlA-9821 - GAGGCAGGCCAGAAAGAGGAGAG 23 13670

SCNNlA-9822 - GGAGGCAGGCCAGAAAGAGGAGAG 24 13671

SCNNlA-9823 - AACAGAAGGCAGAUAGAG 18 13672

SCNNlA-9824 - AAACAGAAGGCAGAUAGAG 19 13673

SCNNlA-5250 - GAAACAGAAGGCAGAUAGAG 20 9099

SCNNlA-9825 - AGAAACAGAAGGCAGAUAGAG 21 13674

SCNNlA-9826 - GAGAAACAGAAGGCAGAUAGAG 22 13675

SCNNlA-9827 - AG AG AAACAGAAGGCAGAUAGAG 23 13676

SCNNlA-9828 - AAGAGAAACAGAAGGCAGAUAGAG 24 13677

SCNNlA-9829 - GGGAGUGAGAGGCAGGAG 18 13678

SCNNlA-9830 - AGGGAGUGAGAGGCAGGAG 19 13679

SCNNlA-9831 - GAGGGAGUGAGAGGCAGGAG 20 13680

SCNNlA-9832 - AGAGGGAGUGAGAGGCAGGAG 21 13681

SCNNlA-9833 - GAGAGGGAGUGAGAGGCAGGAG 22 13682

SCNNlA-9834 - AGAGAGGGAGUGAGAGGCAGGAG 23 13683

SCNNlA-9835 - UAGAGAGGGAGUGAGAGGCAGGAG 24

13684

SCNNlA-9836 - UAGAUAGCCCCAGAGGAG 18 13685

SCNNlA-9837 - GUAGAUAGCCCCAGAGGAG 19 13686

SCNNlA-9838 - AGUAGAUAGCCCCAGAGGAG 20 13687

SCNNlA-9839 - AAGUAGAUAGCCCCAGAGGAG 21 13688

SCNNlA-9840 - UAAGUAGAUAGCCCCAGAGGAG 22 13689

SCNNlA-9841 - CUAAGUAGAUAGCCCCAGAGGAG 23 13690

SCNNlA-9842 - GCUAAGUAGAUAGCCCCAGAGGAG 24 13691

SCNNlA-9843 - GGAGGAGGGAGGGAGGAG 18 13692

SCNNlA-9844 - UGGAGGAGGGAGGGAGGAG 19 13693

SCNNlA-5897 - GUGGAGGAGGGAGGGAGGAG 20 9746

SCNNlA-9845 - GGUGGAGGAGGGAGGGAGGAG 21 13694

SCNNlA-9846 - AGGUGGAGGAGGGAGGGAGGAG 22 13695

SCNNlA-9847 - AAGGUGGAGGAGGGAGGGAGGAG 23 13696

SCNNlA-9848 - AAAGGUGGAGGAGGGAGGGAGGAG 24

13697

SCNNlA-2007 - GGGAACAAGCUGGAGGAG 18 5856

SCNNlA-2008 - GGGGAACAAGCUGGAGGAG 19 5857

SCNNlA-169 - AGGGGAACAAGCUGGAGGAG 20 807

SCNNlA-2009 - AAGGGGAACAAGCUGGAGGAG 21 5858

SCNNlA-2010 - GAAGGGGAACAAGCUGGAGGAG 22 5859

SCNNlA-2011 - UGAAGGGGAACAAGCUGGAGGAG 23 5860

SCNNlA-2012 - AUGAAGGGGAACAAGCUGGAGGAG 24 5861

1458

5535.1 SCNNlA-2013 - GAGGGGAACAAGCUGGAGGAG 21 5862

SCNNlA-2014 - GGAGGGGAACAAGCUGGAGGAG 22 5863

SCNNlA-2015 - UGGAGGGGAACAAGCUGGAGGAG 23 5864

SCNNlA-2016 - AUGGAGGGGAACAAGCUGGAGGAG 24 5865

SCNNlA-9849 - CUGUCAGGUGAGGGGGAG 18 13698

SCNNlA-9850 - CCUGUCAGGUGAGGGGGAG 19 13699

SCNNlA-9851 - ACCUGUCAGGUGAGGGGGAG 20 13700

SCNNlA-9852 - CACCUGUCAGGUGAGGGGGAG 21 13701

SCNNlA-9853 - GCACCUGUCAGGUGAGGGGGAG 22 13702

SCNNlA-9854 - UGCACCUGUCAGGUGAGGGGGAG 23 13703

SCNNlA-9855 - CUGCACCUGUCAGGUGAGGGGGAG 24 13704

SCNNlA-9856 - GCAAGGCAAGGGGGGGAG 18 13705

SCNNlA-9857 - GGCAAGGCAAGGGGGGGAG 19 13706

SCNNlA-5900 - GGGCAAGGCAAGGGGGGGAG 20 9749

SCNNlA-9858 - GGGGCAAGGCAAGGGGGGGAG 21 13707

SCNNlA-9859 - GGGGGCAAGGCAAGGGGGGGAG 22 13708

SCNNlA-9860 - AGGGGGCAAGGCAAGGGGGGGAG 23 13709

SCNNlA-9861 - GAGGGGGCAAGGCAAGGGGGGGAG 24

13710

SCNNlA-9862 - CCAGCCGCAACCUGGGAG 18 13711

SCNNlA-9863 - UCCAGCCGCAACCUGGGAG 19 13712

SCNNlA-5251 - GUCCAGCCGCAACCUGGGAG 20 9100

SCNNlA-9864 - AGUCCAGCCGCAACCUGGGAG 21 13713

SCNNlA-9865 - CAGUCCAGCCGCAACCUGGGAG 22 13714

SCNNlA-9866 - CCAGUCCAGCCGCAACCUGGGAG 23 13715

SCNNlA-9867 - CCCAGUCCAGCCGCAACCUGGGAG 24 13716

SCNNlA-2029 - AUACCAGGUCUCAUGGAG 18 5878

SCNNlA-2030 - CAUACCAGGUCUCAUGGAG 19 5879

SCNNlA-4 - CCAUACCAGGUCUCAUGGAG 20 498

SCNNlA-2031 - CCCAUACCAGGUCUCAUGGAG 21 5880

SCNNlA-2032 - GCCCAUACCAGGUCUCAUGGAG 22 5881

SCNNlA-2033 - AGCCCAUACCAGGUCUCAUGGAG 23 5882

SCNNlA-2034 - CAGCCCAUACCAGGUCUCAUGGAG 24 5883

SCNNlA-9868 - CAGGGCCAGAGGCUGGAG 18 13717

SCNNlA-9869 - UCAGGGCCAGAGGCUGGAG 19 13718

SCNNlA-9870 - GUCAGGGCCAGAGGCUGGAG 20 13719

SCNNlA-9871 - GGUCAGGGCCAGAGGCUGGAG 21 13720

SCNNlA-9872 - AGGUCAGGGCCAGAGGCUGGAG 22 13721

SCNNlA-9873 - GAGGUCAGGGCCAGAGGCUGGAG 23 13722

SCNNlA-9874 - CGAGGUCAGGGCCAGAGGCUGGAG 24 13723

SCNNlA-9875 - GCUCCAGGAAAGGUGGAG 18 13724

SCNNlA-9876 - GGCUCCAGGAAAGGUGGAG 19 13725

1459

5535.1 SCNNlA-9877 - UGGCUCCAGGAAAGGUGGAG 20 13726

SCNNlA-9878 - CUGGCUCCAGGAAAGGUGGAG 21 13727

SCNNlA-9879 - GCUGGCUCCAGGAAAGGUGGAG 22 13728

SCNNlA-9880 - UGCUGGCUCCAGGAAAGGUGGAG 23 13729

SCNNlA-9881 - CUGCUGGCUCCAGGAAAGGUGGAG 24 13730

SCNNlA-9882 - CUGAGGGCCUAGAGUGAG 18 13731

SCNNlA-9883 - GCUGAGGGCCUAGAGUGAG 19 13732

SCNNlA-5657 - AGCUGAGGGCCUAGAGUGAG 20 9506

SCNNlA-9884 - GAGCUGAGGGCCUAGAGUGAG 21 13733

SCNNlA-9885 - GGAGCUGAGGGCCUAGAGUGAG 22 13734

SCNNlA-9886 - UGGAGCUGAGGGCCUAGAGUGAG 23 13735

SCNNlA-9887 - CUGGAGCUGAGGGCCUAGAGUGAG 24 13736

SCNNlA-9888 - CUGCUCCCACUUAGUGAG 18 13737

SCNNlA-9889 - GCUGCUCCCACUUAGUGAG 19 13738

SCNNlA-5658 - CGCUGCUCCCACUUAGUGAG 20 9507

SCNNlA-9890 - GCGCUGCUCCCACUUAGUGAG 21 13739

SCNNlA-9891 - UGCGCUGCUCCCACUUAGUGAG 22 13740

SCNNlA-9892 - GUGCGCUGCUCCCACUUAGUGAG 23 13741

SCNNlA-9893 - AGUGCGCUGCUCCCACUUAGUGAG 24 13742

SCNNlA-9894 - CUGCACCUGUCAGGUGAG 18 13743

SCNNlA-9895 - GCUGCACCUGUCAGGUGAG 19 13744

SCNNlA-5659 - CGCUGCACCUGUCAGGUGAG 20 9508

SCNNlA-9896 - CCGCUGCACCUGUCAGGUGAG 21 13745

SCNNlA-9897 - GCCGCUGCACCUGUCAGGUGAG 22 13746

SCNNlA-9898 - GGCCGCUGCACCUGUCAGGUGAG 23 13747

SCNNlA-9899 - AGGCCGCUGCACCUGUCAGGUGAG 24 13748

SCNNlA-9900 - GCUCCCACUUAGUGAGCG 18 13749

SCNNlA-9901 - UGCUCCCACUUAGUGAGCG 19 13750

SCNNlA-5668 - CUGCUCCCACUUAGUGAGCG 20 9517

SCNNlA-9902 - GCUGCUCCCACUUAGUGAGCG 21 13751

SCNNlA-9903 - CGCUGCUCCCACUUAGUGAGCG 22 13752

SCNNlA-9904 - GCGCUGCUCCCACUUAGUGAGCG 23 13753

SCNNlA-9905 - UGCGCUGCUCCCACUUAGUGAGCG 24 13754

SCNNlA-9906 - G C U G G C A A A U AG A A A AG G 18 13755

SCNNlA-9907 - AG C U G G C A A A U AG A A A AG G 19 13756

SCNNlA-9908 - GAGCUGGCAAAUAGAAAAGG 20 13757

SCNNlA-9909 - UGAGCUGGCAAAUAGAAAAGG 21 13758

SCNNlA-9910 - AUGAGCUGGCAAAUAGAAAAGG 22 13759

SCNNlA-9911 - CAUGAGCUGGCAAAUAGAAAAGG 23 13760

SCNNlA-9912 - GCAUGAGCUGGCAAAUAGAAAAGG 24 13761

SCNNlA-9913 - GAGGAAGAAGACCAAAGG 18 13762

SCNNlA-9914 - GGAGGAAGAAGACCAAAGG 19 13763

1460

5535.1 SCNNlA-9915 - UGGAGGAAGAAGACCAAAGG 20 13764

SCNNlA-9916 - CUGGAGGAAGAAGACCAAAGG 21 13765

SCNNlA-9917 - CCUGGAGGAAGAAGACCAAAGG 22 13766

SCNNlA-9918 - UCCUGGAGGAAGAAGACCAAAGG 23 13767

SCNNlA-9919 - AUCCUGGAGGAAGAAGACCAAAGG 24 13768

SCNNlA-9920 - UGCUGGCUCCAGGAAAGG 18 13769

SCNNlA-9921 - CUGCUGGCUCCAGGAAAGG 19 13770

SCNNlA-6150 - UCUGCUGGCUCCAGGAAAGG 20 9999

SCNNlA-9922 - GUCUGCUGGCUCCAGGAAAGG 21 13771

SCNNlA-9923 - GGUCUGCUGGCUCCAGGAAAGG 22 13772

SCNNlA-9924 - AGGUCUGCUGGCUCCAGGAAAGG 23 13773

SCNNlA-9925 - CAGGUCUGCUGGCUCCAGGAAAGG 24 13774

SCNNlA-9926 - UCCCGGGUCUGGACAAGG 18 13775

SCNNlA-9927 - CUCCCGGGUCUGGACAAGG 19 13776

SCNNlA-9928 - CCUCCCGGGUCUGGACAAGG 20 13777

SCNNlA-9929 - CCCUCCCGGGUCUGGACAAGG 21 13778

SCNNlA-9930 - CCCCUCCCGGGUCUGGACAAGG 22 13779

SCNNlA-9931 - GCCCCUCCCGGGUCUGGACAAGG 23 13780

SCNNlA-9932 - GGCCCCUCCCGGGUCUGGACAAGG 24 13781

SCNNlA-9933 - AGAGGGGGCAAGGCAAGG 18 13782

SCNNlA-9934 - GAGAGGGGGCAAGGCAAGG 19 13783

SCNNlA-6152 - UGAGAGGGGGCAAGGCAAGG 20 10001

SCNNlA-9935 - GUGAGAGGGGGCAAGGCAAGG 21 13784

SCNNlA-9936 - AGUGAGAGGGGGCAAGGCAAGG 22 13785

SCNNlA-9937 - GAGUGAGAGGGGGCAAGGCAAGG 23 13786

SCNNlA-9938 - AGAGUGAGAGGGGGCAAGGCAAGG 24 13787

SCNNlA-9939 - AGGAAGCCACAGACCAGG 18 13788

SCNNlA-9940 - GAGGAAGCCACAGACCAGG 19 13789

SCNNlA-9941 - AGAGGAAGCCACAGACCAGG 20 13790

SCNNlA-9942 - GAGAGGAAGCCACAGACCAGG 21 13791

SCNNlA-9943 - AGAGAGGAAGCCACAGACCAGG 22 13792

SCNNlA-9944 - AAGAGAGGAAGCCACAGACCAGG 23 13793

SCNNlA-9945 - CAAGAGAGGAAGCCACAGACCAGG 24 13794

SCNNlA-9946 - GAAAGAGGAGGGACCAGG 18 13795

SCNNlA-9947 - GGAAAGAGGAGGGACCAGG 19 13796

SCNNlA-6153 - AGGAAAGAGGAGGGACCAGG 20 10002

SCNNlA-9948 - CAGGAAAGAGGAGGGACCAGG 21 13797

SCNNlA-9949 - GCAGGAAAGAGGAGGGACCAGG 22 13798

SCNNlA-9950 - AGCAGGAAAGAGGAGGGACCAGG 23 13799

SCNNlA-9951 - CAGCAGGAAAGAGGAGGGACCAGG 24 13800

SCNNlA-2047 - GGAGAAUGUGGGCGCAGG 18 5896

SCNNlA-2048 - GGGAGAAUGUGGGCGCAGG 19 5897

1461

5535.1 SCNNlA-2049 - UGGGAGAAUGUGGGCGCAGG 20 5898

SCNNlA-9952 - GUGGGAGAAUGUGGGCGCAGG 21 13801

SCNNlA-9953 - AGUGGGAGAAUGUGGGCGCAGG 22 13802

SCNNlA-9954 - GAGUGGGAGAAUGUGGGCGCAGG 23 13803

SCNNlA-9955 - GGAGUGGGAGAAUGUGGGCGCAGG 24

13804

SCNNlA-9956 - UGAGCACCUUAUUGCAGG 18 13805

SCNNlA-9957 - CUGAGCACCUUAUUGCAGG 19 13806

SCNNlA-9958 - GCUGAGCACCUUAUUGCAGG 20 13807

SCNNlA-9959 - UGCUGAGCACCUUAUUGCAGG 21 13808

SCNNlA-9960 - GUGCUGAGCACCUUAUUGCAGG 22 13809

SCNNlA-9961 - GGUGCUGAGCACCUUAUUGCAGG 23 13810

SCNNlA-9962 - GGGUGCUGAGCACCUUAUUGCAGG 24 13811

SCNNlA-9963 - UGUGUAUCAAUGCUCAGG 18 13812

SCNNlA-9964 - GUGUGUAUCAAUGCUCAGG 19 13813

SCNNlA-9965 - GGUGUGUAUCAAUGCUCAGG 20 13814

SCNNlA-9966 - CGGUGUGUAUCAAUGCUCAGG 21 13815

SCNNlA-9967 - CCGGUGUGUAUCAAUGCUCAGG 22 13816

SCNNlA-9968 - CCCGGUGUGUAUCAAUGCUCAGG 23 13817

SCNNlA-9969 - CCCCGGUGUGUAUCAAUGCUCAGG 24 13818

SCNNlA-9970 - G A A U C AG C AG G A A AG AG G 18 13819

SCNNlA-9971 - G G A A U C AG C AG G A A AG AG G 19 13820

SCNNlA-6155 - AGGAAUCAGCAGGAAAGAGG 20 10004

SCNNlA-9972 - GAGGAAUCAGCAGGAAAGAGG 21 13821

SCNNlA-9973 - CGAGGAAUCAGCAGGAAAGAGG 22 13822

SCNNlA-9974 - GCGAGGAAUCAGCAGGAAAGAGG 23 13823

SCNNlA-9975 - GGCGAGGAAUCAGCAGGAAAGAGG 24 13824

SCNNlA-9976 - AGUAGAUAGCCCCAGAGG 18 13825

SCNNlA-9977 - AAGUAGAUAGCCCCAGAGG 19 13826

SCNNlA-5678 - UAAGUAGAUAGCCCCAGAGG 20 9527

SCNNlA-9978 - CUAAGUAGAUAGCCCCAGAGG 21 13827

SCNNlA-9979 - GCUAAGUAGAUAGCCCCAGAGG 22 13828

SCNNlA-9980 - CGCU AAGUAGAUAGCCCCAGAGG 23 13829

SCNNlA-9981 - GCGCUAAGUAGAUAGCCCCAGAGG 24 13830

SCNNlA-9982 - CGAGGUCAGGGCCAGAGG 18 13831

SCNNlA-9983 - UCGAGGUCAGGGCCAGAGG 19 13832

SCNNlA-9984 - CUCGAGGUCAGGGCCAGAGG 20 13833

SCNNlA-9985 - GCUCGAGGUCAGGGCCAGAGG 21 13834

SCNNlA-9986 - AGCUCGAGGUCAGGGCCAGAGG 22 13835

SCNNlA-9987 - CAGCUCGAGGUCAGGGCCAGAGG 23 13836

SCNNlA-9988 - ACAGCUCGAGGUCAGGGCCAGAGG 24 13837

SCNNlA-9989 - AGGCAAGGGGGGGAGAGG 18 13838

1462

5535.1 SCNNlA-9990 - AAGGCAAGGGGGGGAGAGG 19 13839

SCNNlA-9991 - CAAGGCAAGGGGGGGAGAGG 20 13840

SCNNlA-9992 - GCAAGGCAAGGGGGGGAGAGG 21 13841

SCNNlA-9993 - GGCAAGGCAAGGGGGGGAGAGG 22 13842

SCNNlA-9994 - GGGCAAGGCAAGGGGGGGAGAGG 23 13843

SCNNlA-9995 - GGGGCAAGGCAAGGGGGGGAGAGG 24

13844

SCNNlA-9996 - UAGAGAGGGAGUGAGAGG 18 13845

SCNNlA-9997 - AUAGAGAGGGAGUGAGAGG 19 13846

SCNNlA-9998 - GAUAGAGAGGGAGUGAGAGG 20 13847

SCNNlA-9999 - AGAUAGAGAGGGAGUGAGAGG 21 13848

SCNN1A-

- CAGAUAGAGAGGGAGUGAGAGG 22

10000 13849

SCNN1A-

- GCAGAUAGAGAGGGAGUGAGAGG 23

10001 13850

SCNN1A-

- GGCAGAUAGAGAGGGAGUGAGAGG 24

10002 13851

SCNN1A-

- AGAUAGCCCCAGAGGAGG 18

10003 13852

SCNN1A-

- UAGAUAGCCCCAGAGGAGG 19

10004 13853

SCNNlA-5261 - GUAGAUAGCCCCAGAGGAGG 20 9110

SCNN1A-

- AGUAGAUAGCCCCAGAGGAGG 21

10005 13854

SCNN1A-

- AAGUAGAUAGCCCCAGAGGAGG 22

10006 13855

SCNN1A-

- UAAGUAGAUAGCCCCAGAGGAGG 23

10007 13856

SCNN1A-

- CUAAGUAGAUAGCCCCAGAGGAGG 24

10008 13857

SCNN1A-

- CAGGAAAGGUGGAGGAGG 18

10009 13858

SCNN1A-

- CCAGGAAAGGUGGAGGAGG 19

10010 13859

SCNN1A-

- UCCAGGAAAGGUGGAGGAGG 20

10011 13860

SCNN1A-

- CUCCAGGAAAGGUGGAGGAGG 21

10012 13861

SCNN1A-

- GCUCCAGGAAAGGUGGAGGAGG 22

10013 13862

SCNN1A-

- GGCUCCAGGAAAGGUGGAGGAGG 23

10014 13863

SCNN1A- - UGGCUCCAGGAAAGGUGGAGGAGG 24 13864

1463

5535.1 10015

SCNN1A-

- AAAGGUGGAGGAGGGAGG 18

10016 13865

SCNN1A-

- GAAAGGUGGAGGAGGGAGG 19

10017 13866

SCNN1A-

- GGAAAGGUGGAGGAGGGAGG 20

10018 13867

SCNN1A-

- AGGAAAGGUGGAGGAGGGAGG 21

10019 13868

SCNN1A-

- CAGGAAAGGUGGAGGAGGGAGG 22

10020 13869

SCNN1A-

- CCAGGAAAGGUGGAGGAGGGAGG 23

10021 13870

SCNN1A-

- UCCAGGAAAGGUGGAGGAGGGAGG 24

10022 13871

SCNN1A-

- CUGGCUUGUGGAGGGAGG 18

10023 13872

SCNN1A-

- GCUGGCUUGUGGAGGGAGG 19

10024 13873

SCNN1A-

- UGCUGGCUUGUGGAGGGAGG 20

10025 13874

SCNN1A-

- CUGCUGGCUUGUGGAGGGAGG 21

10026 13875

SCNN1A-

- UCUGCUGGCUUGUGGAGGGAGG 22

10027 13876

SCNN1A-

- GUCUGCUGGCUUGUGGAGGGAGG 23

10028 13877

SCNN1A-

- UGUCUGCUGGCUUGUGGAGGGAGG 24

10029 13878

SCNN1A-

- AGACACAGAUCCUGGAGG 18

10030 13879

SCNN1A-

- GAGACACAGAUCCUGGAGG 19

10031 13880

SCNN1A-

- UGAGACACAGAUCCUGGAGG 20

10032 13881

SCNN1A-

- CUGAGACACAGAUCCUGGAGG 21

10033 13882

SCNN1A-

- GCUGAGACACAGAUCCUGGAGG 22

10034 13883

SCNN1A-

- AGCUGAGACACAGAUCCUGGAGG 23

10035 13884

SCNN1A-

- GAGCUGAGACACAGAUCCUGGAGG 24

10036 13885

1464

5535.1 SCNN1A-

- CUCCAGGAAAGGUGGAGG 18

10037 13886

SCNN1A-

- GCUCCAGGAAAGGUGGAGG 19

10038 13887

SCNNlA-5906 - GGCUCCAGGAAAGGUGGAGG 20 9755

SCNN1A-

- UGGCUCCAGGAAAGGUGGAGG 21

10039 13888

SCNN1A-

- CUGGCUCCAGGAAAGGUGGAGG 22

10040 13889

SCNN1A-

- GCUGGCUCCAGGAAAGGUGGAGG 23

10041 13890

SCNN1A-

- UGCUGGCUCCAGGAAAGGUGGAGG 24

10042 13891

SCNN1A-

- UCUCUGCAGGGCCUGAGG 18

10043 13892

SCNN1A-

- UUCUCUGCAGGGCCUGAGG 19

10044 13893

SCNN1A-

- CUUCUCUGCAGGGCCUGAGG 20

10045 13894

SCNN1A-

- UCUUCUCUGCAGGGCCUGAGG 21

10046 13895

SCNN1A-

- CUCUUCUCUGCAGGGCCUGAGG 22

10047 13896

SCNN1A-

- UCUCUUCUCUGCAGGGCCUGAGG 23

10048 13897

SCNN1A-

- CUCUCUUCUCUGCAGGGCCUGAGG 24

10049 13898

SCNN1A-

- UGCACCUGUCAGGUGAGG 18

10050 13899

SCNN1A-

- CUGCACCUGUCAGGUGAGG 19

10051 13900

SCNNlA-5908 - GCUGCACCUGUCAGGUGAGG 20 9757

SCNN1A-

- CGCUGCACCUGUCAGGUGAGG 21

10052 13901

SCNN1A-

- CCGCUGCACCUGUCAGGUGAGG 22

10053 13902

SCNN1A-

- GCCGCUGCACCUGUCAGGUGAGG 23

10054 13903

SCNN1A-

- GGCCGCUGCACCUGUCAGGUGAGG 24

10055 13904

SCNN1A-

- UCCCUGGCCGGCCAGCGG 18

10056 13905

SCNN1A- - AUCCCUGGCCGGCCAGCGG 19 13906

1465

5535.1 10057

SCNN1A-

- CAUCCCUGGCCGGCCAGCGG 20

10058 13907

SCNN1A-

- CCAUCCCUGGCCGGCCAGCGG 21

10059 13908

SCNN1A-

- UCCAUCCCUGGCCGGCCAGCGG 22

10060 13909

SCNN1A-

- UUCCAUCCCUGGCCGGCCAGCGG 23

10061 13910

SCNN1A-

- CUUCCAUCCCUGGCCGGCCAGCGG 24

10062 13911

SCNN1A-

- GAGGGGGCAAGGCAAGGG 18

10063 13912

SCNN1A-

- AGAGGGGGCAAGGCAAGGG 19

10064 13913

SCNNlA-5910 - GAGAGGGGGCAAGGCAAGGG 20 9759

SCNN1A-

- UGAGAGGGGGCAAGGCAAGGG 21

10065 13914

SCNN1A-

- GUGAGAGGGGGCAAGGCAAGGG 22

10066 13915

SCNN1A-

- AGUGAGAGGGGGCAAGGCAAGGG 23

10067 13916

SCNN1A-

- GAGUGAGAGGGGGCAAGGCAAGGG 24

10068 13917

SCNNlA-2068 - GAGAAUGUGGGCGCAGGG 18 5917

SCNNlA-2069 - GGAGAAUGUGGGCGCAGGG 19 5918

SCNNlA-354 - GGGAGAAUGUGGGCGCAGGG 20 4203

SCNNlA-2070 - UGGGAGAAUGUGGGCGCAGGG 21 5919

SCNNlA-2071 - GUGGGAGAAUGUGGGCGCAGGG 22 5920

SCNNlA-2072 - AGUGGGAGAAUGUGGGCGCAGGG 23 5921

SCNNlA-2073 - GAGUGGGAGAAUGUGGGCGCAGGG 24

5922

SCNN1A-

- AGGAAAGGUGGAGGAGGG 18

10069 13918

SCNN1A-

- CAGGAAAGGUGGAGGAGGG 19

10070 13919

SCNNlA-6162 - CCAGGAAAGGUGGAGGAGGG 20 10011

SCNN1A-

- UCCAGGAAAGGUGGAGGAGGG 21

10071 13920

SCNN1A-

- CUCCAGGAAAGGUGGAGGAGGG 22

10072 13921

SCNN1A-

- GCUCCAGGAAAGGUGGAGGAGGG 23

10073 13922

1466

5535.1 SCNN1A-

- GGCUCCAGGAAAGGUGGAGGAGGG 24

10074 13923

SCNN1A-

- UCCCACUUAGUGAGCGGG 18

10075 13924

SCNN1A-

- CUCCCACUUAGUGAGCGGG 19

10076 13925

SCNN1A-

- GCUCCCACUUAGUGAGCGGG 20

10077 13926

SCNN1A-

- UGCUCCCACUUAGUGAGCGGG 21

10078 13927

SCNN1A-

- CUGCUCCCACUUAGUGAGCGGG 22

10079 13928

SCNN1A-

- GCUGCUCCCACUUAGUGAGCGGG 23

10080 13929

SCNN1A-

- CGCUGCUCCCACUUAGUGAGCGGG 24

10081 13930

SCNN1A-

- AGGGGGCAAGGCAAGGGG 18

10082 13931

SCNN1A-

- GAGGGGGCAAGGCAAGGGG 19

10083 13932

SCNNlA-6163 - AGAGGGGGCAAGGCAAGGGG 20 10012

SCNN1A-

- GAGAGGGGGCAAGGCAAGGGG 21

10084 13933

SCNN1A-

- UGAGAGGGGGCAAGGCAAGGGG 22

10085 13934

SCNN1A-

- GUGAGAGGGGGCAAGGCAAGGGG 23

10086 13935

SCNN1A-

- AGUGAGAGGGGGCAAGGCAAGGGG 24

10087 13936

SCNN1A-

- CACCUGUCAGGUGAGGGG 18

10088 13937

SCNN1A-

- GCACCUGUCAGGUGAGGGG 19

10089 13938

SCNN1A-

- UGCACCUGUCAGGUGAGGGG 20

10090 13939

SCNN1A-

- CUGCACCUGUCAGGUGAGGGG 21

10091 13940

SCNN1A-

- GCUGCACCUGUCAGGUGAGGGG 22

10092 13941

SCNN1A-

- CGCUGCACCUGUCAGGUGAGGGG 23

10093 13942

SCNN1A-

- CCGCUGCACCUGUCAGGUGAGGGG 24

10094 13943

1467

5535.1 SCNN1A-

- CCCACUUAGUGAGCGGGG 18

10095 13944

SCNN1A-

- UCCCACUUAGUGAGCGGGG 19

10096 13945

SCNNlA-5689 - CUCCCACUUAGUGAGCGGGG 20 9538

SCNN1A-

- GCUCCCACUUAGUGAGCGGGG 21

10097 13946

SCNN1A-

- UGCUCCCACUUAGUGAGCGGGG 22

10098 13947

SCNN1A-

- CUGCUCCCACUUAGUGAGCGGGG 23

10099 13948

SCNN1A-

- GCUGCUCCCACUUAGUGAGCGGGG 24

10100 13949

SCNN1A-

- AAGACCAAAGGAAGGGGG 18

10101 13950

SCNN1A-

- GAAGACCAAAGGAAGGGGG 19

10102 13951

SCNN1A-

- AGAAGACCAAAGGAAGGGGG 20

10103 13952

SCNN1A-

- AAGAAGACCAAAGGAAGGGGG 21

10104 13953

SCNN1A-

- GAAGAAGACCAAAGGAAGGGGG 22

10105 13954

SCNN1A-

- GGAAGAAGACCAAAGGAAGGGGG 23

10106 13955

SCNN1A-

- AGGAAGAAGACCAAAGGAAGGGGG 24

10107 13956

SCNN1A-

- ACCUGUCAGGUGAGGGGG 18

10108 13957

SCNN1A-

- CACCUGUCAGGUGAGGGGG 19

10109 13958

SCNNlA-5914 - GCACCUGUCAGGUGAGGGGG 20 9763

SCNN1A-

- UGCACCUGUCAGGUGAGGGGG 21

10110 13959

SCNN1A-

- CUGCACCUGUCAGGUGAGGGGG 22

10111 13960

SCNN1A-

- GCUGCACCUGUCAGGUGAGGGGG 23

10112 13961

SCNN1A-

- CGCUGCACCUGUCAGGUGAGGGGG 24

10113 13962

SCNN1A-

- GGGGCAAGGCAAGGGGGG 18

10114 13963

SCNN1A- - GGGGGCAAGGCAAGGGGGG 19 13964

1468

5535.1 10115

SCNN1A-

- AGGGGGCAAGGCAAGGGGGG 20

10116 13965

SCNN1A-

- GAGGGGGCAAGGCAAGGGGGG 21

10117 13966

SCNN1A-

- AGAGGGGGCAAGGCAAGGGGGG 22

10118 13967

SCNN1A-

- GAGAGGGGGCAAGGCAAGGGGGG 23

10119 13968

SCNN1A-

- UGAGAGGGGGCAAGGCAAGGGGGG 24

10120 13969

SCNN1A-

- AGCCCUGCAGUCCUGGGG 18

10121 13970

SCNN1A-

- GAGCCCUGCAGUCCUGGGG 19

10122 13971

SCNN1A-

- GGAGCCCUGCAGUCCUGGGG 20

10123 13972

SCNN1A-

- UGGAGCCCUGCAGUCCUGGGG 21

10124 13973

SCNN1A-

- CUGGAGCCCUGCAGUCCUGGGG 22

10125 13974

SCNN1A-

- CCUGGAGCCCUGCAGUCCUGGGG 23

10126 13975

SCNN1A-

- UCCUGGAGCCCUGCAGUCCUGGGG 24

10127 13976

SCNNlA-2080 - CCAUACCAGGUCUCAUGG 18 5929

SCNNlA-2081 - CCCAUACCAGGUCUCAUGG 19 5930

SCNNlA-2 - GCCCAUACCAGGUCUCAUGG 20 497

SCNNlA-2082 - AGCCCAUACCAGGUCUCAUGG 21 5931

SCNNlA-2083 - CAGCCCAUACCAGGUCUCAUGG 22 5932

SCNNlA-2084 - GCAGCCCAUACCAGGUCUCAUGG 23 5933

SCNNlA-2085 - UGCAGCCCAUACCAGGUCUCAUGG 24 5934

SCNNlA-2086 - GGGUUCCAGGGGUGAUGG 18 5935

SCNNlA-2087 - CGGGUUCCAGGGGUGAUGG 19 5936

SCNNlA-2088 - UCGGGUUCCAGGGGUGAUGG 20 5937

SCNNlA-2089 - CUCGGGUUCCAGGGGUGAUGG 21 5938

SCNNlA-2090 - ACUCGGGUUCCAGGGGUGAUGG 22 5939

SCNNlA-2091 - CACUCGGGUUCCAGGGGUGAUGG 23 5940

SCNNlA-2092 - UCACUCGGGUUCCAGGGGUGAUGG 24 5941

SCNN1A-

- CUGAGACACAGAUCCUGG 18

10128 13977

SCNN1A-

- GCUGAGACACAGAUCCUGG 19

10129 13978

1469

5535.1 SCNNlA-5693 - AGCUGAGACACAGAUCCUGG 20 9542

SCNN1A-

- GAGCUGAGACACAGAUCCUGG 21

10130 13979

SCNN1A-

- GGAGCUGAGACACAGAUCCUGG 22

10131 13980

SCNN1A-

- AGGAGCUGAGACACAGAUCCUGG 23

10132 13981

SCNN1A-

- CAGGAGCUGAGACACAGAUCCUGG 24

10133 13982

SCNNlA-2093 - UGAAGGGGAACAAGCUGG 18 5942

SCNNlA-2094 - AUGAAGGGGAACAAGCUGG 19 5943

SCNNlA-455 - CAUGAAGGGGAACAAGCUGG 20 4304

SCNNlA-2095 - UCAUGAAGGGGAACAAGCUGG 21 5944

SCNNlA-2096 - CUCAUGAAGGGGAACAAGCUGG 22 5945

SCNNlA-2097 - GCUCAUGAAGGGGAACAAGCUGG 23 5946

SCNNlA-2098 - GGCUCAUGAAGGGGAACAAGCUGG 24 5947

SCNNlA-2099 - UGGAGGGGAACAAGCUGG 18 5948

SCNNlA-2100 - AUGGAGGGGAACAAGCUGG 19 5949

SCNNlA-6 - CAUGGAGGGGAACAAGCUGG 20 558

SCNNlA-2101 - UCAUGGAGGGGAACAAGCUGG 21 5950

SCNNlA-2102 - CUCAUGGAGGGGAACAAGCUGG 22 5951

SCNNlA-2103 - UCUCAUGGAGGGGAACAAGCUGG 23 5952

SCNNlA-2104 - GUCUCAUGGAGGGGAACAAGCUGG 24 5953

SCNN1A-

- UGGCUCCAGGAAAGGUGG 18

10134 13983

SCNN1A-

- CUGGCUCCAGGAAAGGUGG 19

10135 13984

SCNNlA-5266 - GCUGGCUCCAGGAAAGGUGG 20 9115

SCNN1A-

- UGCUGGCUCCAGGAAAGGUGG 21

10136 13985

SCNN1A-

- CUGCUGGCUCCAGGAAAGGUGG 22

10137 13986

SCNN1A-

- UCUGCUGGCUCCAGGAAAGGUGG 23

10138 13987

SCNN1A-

- GUCUGCUGGCUCCAGGAAAGGUGG 24

10139 13988

SCNN1A-

- UUGUCUGCUGGCUUGUGG 18

10140 13989

SCNN1A-

- UUUGUCUGCUGGCUUGUGG 19

10141 13990

SCNNlA-5695 - CUUUGUCUGCUGGCUUGUGG 20 9544

SCNN1A-

- CCUUUGUCUGCUGGCUUGUGG 21

10142 13991

1470

5535.1 SCNN1A-

- GCCUUUGUCUGCUGGCUUGUGG 22

10143 13992

SCNN1A-

- GGCCUUUGUCUGCUGGCUUGUGG 23

10144 13993

SCNN1A-

- GGGCCUUUGUCUGCUGGCUUGUGG 24

10145 13994

SCNN1A-

- GGGUCUGGACAAGGUUGG 18

10146 13995

SCNN1A-

- CGGGUCUGGACAAGGUUGG 19

10147 13996

SCNNlA-5697 - CCGGGUCUGGACAAGGUUGG 20 9546

SCNN1A-

- CCCGGGUCUGGACAAGGUUGG 21

10148 13997

SCNN1A-

- UCCCGGGUCUGGACAAGGUUGG 22

10149 13998

SCNN1A-

- CUCCCGGGUCUGGACAAGGUUGG 23

10150 13999

SCNN1A-

- CCUCCCGGGUCUGGACAAGGUUGG 24

10151 14000

SCNN1A-

- UUCUUCAUUAGGACAAUG 18

10152 14001

SCNN1A-

- UUUCUUCAUUAGGACAAUG 19

10153 14002

SCNN1A-

- GUUUCUUCAUUAGGACAAUG 20

10154 14003

SCNN1A-

- AGUUUCUUCAUUAGGACAAUG 21

10155 14004

SCNN1A-

- CAGUUUCUUCAUUAGGACAAUG 22

10156 14005

SCNN1A-

- UCAGUUUCUUCAUUAGGACAAUG 23

10157 14006

SCNN1A-

- GUCAGUUUCUUCAUUAGGACAAUG 24

10158 14007

SCNNlA-2111 - UCCACUCCGGGGCUCAUG 18 5960

SCNNlA-2112 - AUCCACUCCGGGGCUCAUG 19 5961

SCNNlA-2113 - AAUCCACUCCGGGGCUCAUG 20 5962

SCNNlA-2114 - CAAUCCACUCCGGGGCUCAUG 21 5963

SCNNlA-2115 - CCAAUCCACUCCGGGGCUCAUG 22 5964

SCNNlA-2116 - CCCAAUCCACUCCGGGGCUCAUG 23 5965

SCNNlA-2117 - CCCCAAUCCACUCCGGGGCUCAUG 24 5966

SCNNlA-2118 - CCCAUACCAGGUCUCAUG 18 5967

SCNNlA-2119 - GCCCAUACCAGGUCUCAUG 19 5968

SCNNlA-161 - AGCCCAUACCAGGUCUCAUG 20 804

1471

5535.1 SCNNlA-2120 - CAGCCCAUACCAGGUCUCAUG 21 5969

SCNNlA-2121 - GCAGCCCAUACCAGGUCUCAUG 22 5970

SCNNlA-2122 - UGCAGCCCAUACCAGGUCUCAUG 23 5971

SCNNlA-2123 - CUGCAGCCCAUACCAGGUCUCAUG 24 5972

SCNN1A-

- AGGGGUCUCUGGGAUAUG 18

10159 14008

SCNN1A-

- UAGGGGUCUCUGGGAUAUG 19

10160 14009

SCNNlA-5700 - CUAGGGGUCUCUGGGAUAUG 20 9549

SCNN1A-

- UCU AGGGGUCUCUGGGAUAUG 21

10161 14010

SCNN1A-

- UUCUAGGGGUCUCUGGGAUAUG 22

10162 14011

SCNN1A-

- UUUCUAGGGGUCUCUGGGAUAUG 23

10163 14012

SCNN1A-

- GUUUCUAGGGGUCUCUGGGAUAUG 24

10164 14013

SCNN1A-

- GAGCGGGGAGGAGACCUG 18

10165 14014

SCNN1A-

- UGAGCGGGGAGGAGACCUG 19

10166 14015

SCNN1A-

- GUGAGCGGGGAGGAGACCUG 20

10167 14016

SCNN1A-

- AGUGAGCGGGGAGGAGACCUG 21

10168 14017

SCNN1A-

- UAGUGAGCGGGGAGGAGACCUG 22

10169 14018

SCNN1A-

- UUAGUGAGCGGGGAGGAGACCUG 23

10170 14019

SCNN1A-

- CUUAGUGAGCGGGGAGGAGACCUG 24

10171 14020

SCNN1A-

- GCUGAGACACAGAUCCUG 18

10172 14021

SCNN1A-

- AGCUGAGACACAGAUCCUG 19

10173 14022

SCNN1A-

- GAGCUGAGACACAGAUCCUG 20

10174 14023

SCNN1A-

- GGAGCUGAGACACAGAUCCUG 21

10175 14024

SCNN1A-

- AGGAGCUGAGACACAGAUCCUG 22

10176 14025

SCNN1A-

- CAGGAGCUGAGACACAGAUCCUG 23

10177 14026

1472

5535.1 SCNN1A-

- GCAGGAGCUGAGACACAGAUCCUG 24

10178 14027

SCNN1A-

- ACUCUGGGCUGCCUCCUG 18

10179 14028

SCNN1A-

- CACUCUGGGCUGCCUCCUG 19

10180 14029

SCNNlA-5269 - GCACUCUGGGCUGCCUCCUG 20 9118

SCNN1A-

- UGCACUCUGGGCUGCCUCCUG 21

10181 14030

SCNN1A-

- CUGCACUCUGGGCUGCCUCCUG 22

10182 14031

SCNN1A-

- CCUGCACUCUGGGCUGCCUCCUG 23

10183 14032

SCNN1A-

- UCCUGCACUCUGGGCUGCCUCCUG 24

10184 14033

SCNNlA-2124 - AUGAAGGGGAACAAGCUG 18 5973

SCNNlA-2125 - CAUGAAGGGGAACAAGCUG 19 5974

SCNNlA-2126 - UCAUGAAGGGGAACAAGCUG 20 5975

SCNNlA-2127 - CUCAUGAAGGGGAACAAGCUG 21 5976

SCNNlA-2128 - GCUCAUGAAGGGGAACAAGCUG 22 5977

SCNNlA-2129 - GGCUCAUGAAGGGGAACAAGCUG 23 5978

SCNNlA-2130 - GGGCUCAUGAAGGGGAACAAGCUG 24 5979

SCNNlA-2131 - AUGGAGGGGAACAAGCUG 18 5980

SCNNlA-2132 - CAUGGAGGGGAACAAGCUG 19 5981

SCNNlA-167 - UCAUGGAGGGGAACAAGCUG 20 806

SCNNlA-2133 - CUCAUGGAGGGGAACAAGCUG 21 5982

SCNNlA-2134 - UCUCAUGGAGGGGAACAAGCUG 22 5983

SCNNlA-2135 - GUCUCAUGGAGGGGAACAAGCUG 23 5984

SCNNlA-2136 - GGUCUCAUGGAGGGGAACAAGCUG 24 5985

SCNN1A-

- CCUCUUCUCUCUUCUCUG 18

10185 14034

SCNN1A-

- ACCUCUUCUCUCUUCUCUG 19

10186 14035

SCNN1A-

- GACCUCUUCUCUCUUCUCUG 20

10187 14036

SCNN1A-

- AGACCUCUUCUCUCUUCUCUG 21

10188 14037

SCNN1A-

- GAGACCUCUUCUCUCUUCUCUG 22

10189 14038

SCNN1A-

- AGAGACCUCUUCUCUCUUCUCUG 23

10190 14039

SCNN1A-

- CAGAGACCUCUUCUCUCUUCUCUG 24

10191 14040

1473

5535.1 SCNN1A-

- GGGGCAGUGGGGACAGUG 18

10192 14041

SCNN1A-

- UGGGGCAGUGGGGACAGUG 19

10193 14042

SCNN1A-

- GUGGGGCAGUGGGGACAGUG 20

10194 14043

SCNN1A-

- UGUGGGGCAGUGGGGACAGUG 21

10195 14044

SCNN1A-

- AUGUGGGGCAGUGGGGACAGUG 22

10196 14045

SCNN1A-

- UAUGUGGGGCAGUGGGGACAGUG 23

10197 14046

SCNN1A-

- AUAUGUGGGGCAGUGGGGACAGUG 24

10198 14047

SCNN1A-

- GGGCUCUGUGUGGGAGUG 18

10199 14048

SCNN1A-

- CGGGCUCUGUGUGGGAGUG 19

10200 14049

SCNNlA-5711 - ACGGGCUCUGUGUGGGAGUG 20 9560

SCNN1A-

- CACGGGCUCUGUGUGGGAGUG 21

10201 14050

SCNN1A-

- CCACGGGCUCUGUGUGGGAGUG 22

10202 14051

SCNN1A-

- UCCACGGGCUCUGUGUGGGAGUG 23

10203 14052

SCNN1A-

- AUCCACGGGCUCUGUGUGGGAGUG 24

10204 14053

SCNN1A-

- CCUCCUGUGGGGCCCGUG 18

10205 14054

SCNN1A-

- GCCUCCUGUGGGGCCCGUG 19

10206 14055

SCNNlA-5712 - UGCCUCCUGUGGGGCCCGUG 20 9561

SCNN1A-

- CUGCCUCCUGUGGGGCCCGUG 21

10207 14056

SCNN1A-

- GCUGCCUCCUGUGGGGCCCGUG 22

10208 14057

SCNN1A-

- GGCUGCCUCCUGUGGGGCCCGUG 23

10209 14058

SCNN1A-

- GGGCUGCCUCCUGUGGGGCCCGUG 24

10210 14059

SCNN1A-

- AGCCUUCCCUGCCGCGUG 18

10211 14060

SCNN1A- - CAGCCUUCCCUGCCGCGUG 19 14061

1474

5535.1 10212

SCNN1A-

- GCAGCCUUCCCUGCCGCGUG 20

10213 14062

SCNN1A-

- GGCAGCCUUCCCUGCCGCGUG 21

10214 14063

SCNN1A-

- CGGCAGCCUUCCCUGCCGCGUG 22

10215 14064

SCNN1A-

- GCGGCAGCCUUCCCUGCCGCGUG 23

10216 14065

SCNN1A-

- AGCGGCAGCCUUCCCUGCCGCGUG 24

10217 14066

SCNN1A-

- CUGGCUCCAGGAAAGGUG 18

10218 14067

SCNN1A-

- GCUGGCUCCAGGAAAGGUG 19

10219 14068

SCNN1A-

- UGCUGGCUCCAGGAAAGGUG 20

10220 14069

SCNN1A-

- CUGCUGGCUCCAGGAAAGGUG 21

10221 14070

SCNN1A-

- UCUGCUGGCUCCAGGAAAGGUG 22

10222 14071

SCNN1A-

- GUCUGCUGGCUCCAGGAAAGGUG 23

10223 14072

SCNN1A-

- GGUCUGCUGGCUCCAGGAAAGGUG 24

10224 14073

SCNN1A-

- CGCUGCACCUGUCAGGUG 18

10225 14074

SCNN1A-

- CCGCUGCACCUGUCAGGUG 19

10226 14075

SCNNlA-5270 - GCCGCUGCACCUGUCAGGUG 20 9119

SCNN1A-

- GGCCGCUGCACCUGUCAGGUG 21

10227 14076

SCNN1A-

- AGGCCGCUGCACCUGUCAGGUG 22

10228 14077

SCNN1A-

- CAGGCCGCUGCACCUGUCAGGUG 23

10229 14078

SCNN1A-

- CCAGGCCGCUGCACCUGUCAGGUG 24

10230 14079

SCNN1A-

- GAUCAAACAGCCAGGGUG 18

10231 14080

SCNN1A-

- AGAUCAAACAGCCAGGGUG 19

10232 14081

SCNN1A- - GAGAUCAAACAGCCAGGGUG 20 14082

1475

5535.1 10233

SCNN1A-

- UGAGAUCAAACAGCCAGGGUG 21

10234 14083

SCNN1A-

- UUGAGAUCAAACAGCCAGGGUG 22

10235 14084

SCNN1A-

- UUUGAGAUCAAACAGCCAGGGUG 23

10236 14085

SCNN1A-

- CUUUGAGAUCAAACAGCCAGGGUG 24

10237 14086

SCNNlA-2143 - ACUCGGGUUCCAGGGGUG 18 5992

SCNNlA-2144 - CACUCGGGUUCCAGGGGUG 19 5993

SCNNlA-2145 - UCACUCGGGUUCCAGGGGUG 20 5994

SCNNlA-2146 - CUCACUCGGGUUCCAGGGGUG 21 5995

SCNNlA-2147 - CCUCACUCGGGUUCCAGGGGUG 22 5996

SCNNlA-2148 - GCCUCACUCGGGUUCCAGGGGUG 23 5997

SCNNlA-2149 - AGCCUCACUCGGGUUCCAGGGGUG 24 5998

SCNN1A-

- ACAAGGUUGGAGGGGGUG 18

10238 14087

SCNN1A-

- GACAAGGUUGGAGGGGGUG 19

10239 14088

SCNN1A-

- GGACAAGGUUGGAGGGGGUG 20

10240 14089

SCNN1A-

- UGGACAAGGUUGGAGGGGGUG 21

10241 14090

SCNN1A-

- CUGGACAAGGUUGGAGGGGGUG 22

10242 14091

SCNN1A-

- UCUGGACAAGGUUGGAGGGGGUG 23

10243 14092

SCNN1A-

- GUCUGGACAAGGUUGGAGGGGGUG 24

10244 14093

SCNN1A-

- GAAUCCACGGGCUCUGUG 18

10245 14094

SCNN1A-

- CGAAUCCACGGGCUCUGUG 19

10246 14095

SCNNlA-5717 - ACGAAUCCACGGGCUCUGUG 20 9566

SCNN1A-

- GACGAAUCCACGGGCUCUGUG 21

10247 14096

SCNN1A-

- AGACGAAUCCACGGGCUCUGUG 22

10248 14097

SCNN1A-

- CAGACGAAUCCACGGGCUCUGUG 23

10249 14098

SCNN1A-

- GCAGACGAAUCCACGGGCUCUGUG 24

10250 14099

1476

5535.1 SCNN1A-

- UUUGUCUGCUGGCUUGUG 18

10251 14100

SCNN1A-

- CUUUGUCUGCUGGCUUGUG 19

10252 14101

SCNN1A-

- CCUUUGUCUGCUGGCUUGUG 20

10253 14102

SCNN1A-

- GCCUUUGUCUGCUGGCUUGUG 21

10254 14103

SCNN1A-

- GGCCUUUGUCUGCUGGCUUGUG 22

10255 14104

SCNN1A-

- GGGCCUUUGUCUGCUGGCUUGUG 23

10256 14105

SCNN1A-

- UGGGCCUUUGUCUGCUGGCUUGUG 24

10257 14106

SCNN1A-

- GUGCUGAGCACCUUAUUG 18

10258 14107

SCNN1A-

- GGUGCUGAGCACCUUAUUG 19

10259 14108

SCNN1A-

- GGGUGCUGAGCACCUUAUUG 20

10260 14109

SCNN1A-

- AGGGUGCUGAGCACCUUAUUG 21

10261 14110

SCNN1A-

- CAGGGUGCUGAGCACCUUAUUG 22

10262 14111

SCNN1A-

- CCAGGGUGCUGAGCACCUUAUUG 23

10263 14112

SCNN1A-

- GCCAGGGUGCUGAGCACCUUAUUG 24

10264 14113

SCNN1A-

- UGGAGGGCUGCCCACUUG 18

10265 14114

SCNN1A-

- UUGGAGGGCUGCCCACUUG 19

10266 14115

SCNN1A-

- CUUGGAGGGCUGCCCACUUG 20

10267 14116

SCNN1A-

- CCUUGGAGGGCUGCCCACUUG 21

10268 14117

SCNN1A-

- CCCUUGGAGGGCUGCCCACUUG 22

10269 14118

SCNN1A-

- GCCCUUGGAGGGCUGCCCACUUG 23

10270 14119

SCNN1A-

- UGCCCUUGGAGGGCUGCCCACUUG 24

10271 14120

SCNN1A- - GACCUGUGGGUGCCCUUG 18 14121

1477

5535.1 10272

SCNN1A-

- UGACCUGUGGGUGCCCUUG 19

10273 14122

SCNN1A-

- CUGACCUGUGGGUGCCCUUG 20

10274 14123

SCNN1A-

- GCUGACCUGUGGGUGCCCUUG 21

10275 14124

SCNN1A-

- GGCUGACCUGUGGGUGCCCUUG 22

10276 14125

SCNN1A-

- AGGCUGACCUGUGGGUGCCCUUG 23

10277 14126

SCNN1A-

- GAGGCUGACCUGUGGGUGCCCUUG 24

10278 14127

SCNN1A-

- CCUUUGUCUGCUGGCUUG 18

10279 14128

SCNN1A-

- GCCUUUGUCUGCUGGCUUG 19

10280 14129

SCNNlA-5271 - GGCCUUUGUCUGCUGGCUUG 20 9120

SCNN1A-

- GGGCCUUUGUCUGCUGGCUUG 21

10281 14130

SCNN1A-

- UGGGCCUUUGUCUGCUGGCUUG 22

10282 14131

SCNN1A-

- CUGGGCCUUUGUCUGCUGGCUUG 23

10283 14132

SCNN1A-

- GCUGGGCCUUUGUCUGCUGGCUUG 24

10284 14133

SCNN1A-

- CGGGUCUGGACAAGGUUG 18

10285 14134

SCNN1A-

- CCGGGUCUGGACAAGGUUG 19

10286 14135

SCNN1A-

- CCCGGGUCUGGACAAGGUUG 20

10287 14136

SCNN1A-

- UCCCGGGUCUGGACAAGGUUG 21

10288 14137

SCNN1A-

- CUCCCGGGUCUGGACAAGGUUG 22

10289 14138

SCNN1A-

- CCUCCCGGGUCUGGACAAGGUUG 23

10290 14139

SCNN1A-

- CCCUCCCGGGUCUGGACAAGGUUG 24

10291 14140

SCNN1A-

- GUUUGGAAAGAGAUUUUG 18

10292 14141

SCNN1A- - AGUUUGGAAAGAGAUUUUG 19 14142

1478

5535.1 10293

SCNN1A-

- AAGUUUGGAAAGAGAUUUUG 20

10294 14143

SCNN1A-

- UAAGUUUGGAAAGAGAUUUUG 21

10295 14144

SCNN1A-

- UU AAGUUUGGAAAGAGAUUUUG 22

10296 14145

SCNN1A-

- AUUAAGUUUGGAAAGAGAUUUUG 23

10297 14146

SCNN1A-

- CAU U AAG U U UGG AAAG AG AU U U UG 24

10298 14147

SCNN1A-

- GUCUUAUCUCUGAGAAAU 18

10299 14148

SCNN1A-

- UGUCUUAUCUCUGAGAAAU 19

10300 14149

SCNN1A-

- AUGUCUUAUCUCUGAGAAAU 20

10301 14150

SCNN1A-

- UAUGUCUUAUCUCUGAGAAAU 21

10302 14151

SCNN1A-

- UUAUGUCUUAUCUCUGAGAAAU 22

10303 14152

SCNN1A-

- CUUAUGUCUUAUCUCUGAGAAAU 23

10304 14153

SCNN1A-

- UCUUAUGUCUUAUCUCUGAGAAAU 24

10305 14154

SCNN1A-

- CUGGGGCAGAGACAGAAU 18

10306 14155

SCNN1A-

- CCUGGGGCAGAGACAGAAU 19

10307 14156

SCNN1A-

- UCCUGGGGCAGAGACAGAAU 20

10308 14157

SCNN1A-

- GUCCUGGGGCAGAGACAGAAU 21

10309 14158

SCNN1A-

- AGUCCUGGGGCAGAGACAGAAU 22

10310 14159

SCNN1A-

- CAGUCCUGGGGCAGAGACAGAAU 23

10311 14160

SCNN1A-

- GCAGUCCUGGGGCAGAGACAGAAU 24

10312 14161

SCNN1A-

- AGGGAGGAGUGGGAGAAU 18

10313 14162

SCNN1A-

- GAGGGAGGAGUGGGAGAAU 19

10314 14163

1479

5535.1 SCNN1A-

- GGAGGGAGGAGUGGGAGAAU 20

10315 14164

SCNN1A-

- GGGAGGGAGGAGUGGGAGAAU 21

10316 14165

SCNN1A-

- AGGGAGGGAGGAGUGGGAGAAU 22

10317 14166

SCNN1A-

- GAGGGAGGGAGGAGUGGGAGAAU 23

10318 14167

SCNN1A-

- GGAGGGAGGGAGGAGUGGGAGAAU 24

10319 14168

SCNN1A-

- AAGGGUCAGUUUCUUCAU 18

10320 14169

SCNN1A-

- GAAGGGUCAGUUUCUUCAU 19

10321 14170

SCNN1A-

- GGAAGGGUCAGUUUCUUCAU 20

10322 14171

SCNN1A-

- GGGAAGGGUCAGUUUCUUCAU 21

10323 14172

SCNN1A-

- UGGGAAGGGUCAGUUUCUUCAU 22

10324 14173

SCNN1A-

- UUGGGAAGGGUCAGUUUCUUCAU 23

10325 14174

SCNN1A-

- CUUGGGAAGGGUCAGUUUCUUCAU 24

10326 14175

SCNN1A-

- GAGGAAGAGAGGCAGGAU 18

10327 14176

SCNN1A-

- AGAGGAAGAGAGGCAGGAU 19

10328 14177

SCNN1A-

- GAGAGGAAGAGAGGCAGGAU 20

10329 14178

SCNN1A-

- GGAGAGGAAGAGAGGCAGGAU 21

10330 14179

SCNN1A-

- GGGAGAGGAAGAGAGGCAGGAU 22

10331 14180

SCNN1A-

- GGGGAGAGGAAGAGAGGCAGGAU 23

10332 14181

SCNN1A-

- GGGGGAGAGGAAGAGAGGCAGGAU 24

10333 14182

SCNNlA-2150 - UCGGGUUCCAGGGGUGAU 18 5999

SCNNlA-2151 - CUCGGGUUCCAGGGGUGAU 19 6000

SCNNlA-421 - ACUCGGGUUCCAGGGGUGAU 20 4270

SCNNlA-2152 - CACUCGGGUUCCAGGGGUGAU 21 6001

SCNNlA-2153 - UCACUCGGGUUCCAGGGGUGAU 22 6002

1480

5535.1 SCNNlA-2154 - CUCACUCGGGUUCCAGGGGUGAU 23 6003

SCNNlA-2155 - CCUCACUCGGGUUCCAGGGGUGAU 24 6004

SCNN1A-

- UCUCACAGAGCCCUUGAU 18

10334 14183

SCNN1A-

- UUCUCACAGAGCCCUUGAU 19

10335 14184

SCNN1A-

- CUUCUCACAGAGCCCUUGAU 20

10336 14185

SCNN1A-

- UCUUCUCACAGAGCCCUUGAU 21

10337 14186

SCNN1A-

- UUCUUCUCACAGAGCCCUUGAU 22

10338 14187

SCNN1A-

- AUUCUUCUCACAGAGCCCUUGAU 23

10339 14188

SCNN1A-

- AAUUCUUCUCACAGAGCCCUUGAU 24

10340 14189

SCNN1A-

- UAGGGGUCUCUGGGAUAU 18

10341 14190

SCNN1A-

- CUAGGGGUCUCUGGGAUAU 19

10342 14191

SCNN1A-

- UCUAGGGGUCUCUGGGAUAU 20

10343 14192

SCNN1A-

- UUCUAGGGGUCUCUGGGAUAU 21

10344 14193

SCNN1A-

- UUUCUAGGGGUCUCUGGGAUAU 22

10345 14194

SCNN1A-

- GUUUCUAGGGGUCUCUGGGAUAU 23

10346 14195

SCNN1A-

- AGUUUCUAGGGGUCUCUGGGAUAU 24

10347 14196

SCNN1A-

- CUCGAAAGGUGGCCCUAU 18

10348 14197

SCNN1A-

- ACUCGAAAGGUGGCCCUAU 19

10349 14198

SCNN1A-

- AACUCGAAAGGUGGCCCUAU 20

10350 14199

SCNN1A-

- AAACUCGAAAGGUGGCCCUAU 21

10351 14200

SCNN1A-

- AAAACUCGAAAGGUGGCCCUAU 22

10352 14201

SCNN1A-

- CAAAACUCGAAAGGUGGCCCUAU 23

10353 14202

SCNN1A- - ACAAAACUCGAAAGGUGGCCCUAU 24 14203

1481

5535.1 10354

SCNN1A-

- AGCUCCUGGAAGCACACU 18

10355 14204

SCNN1A-

- UAGCUCCUGGAAGCACACU 19

10356 14205

SCNNlA-5727 - CUAGCUCCUGGAAGCACACU 20 9576

SCNN1A-

- UCUAGCUCCUGGAAGCACACU 21

10357 14206

SCNN1A-

- CUCUAGCUCCUGGAAGCACACU 22

10358 14207

SCNN1A-

- CCUCUAGCUCCUGGAAGCACACU 23

10359 14208

SCNN1A-

- GCCUCUAGCUCCUGGAAGCACACU 24

10360 14209

SCNNlA-2156 - UGCUCUCCCCAAUCCACU 18 6005

SCNNlA-2157 - UUGCUCUCCCCAAUCCACU 19 6006

SCNNlA-2158 - CUUGCUCUCCCCAAUCCACU 20 6007

SCNNlA-2159 - CCUUGCUCUCCCCAAUCCACU 21 6008

SCNNlA-2160 - CCCUUGCUCUCCCCAAUCCACU 22 6009

SCNNlA-2161 - ACCCUUGCUCUCCCCAAUCCACU 23 6010

SCNNlA-2162 - GACCCUUGCUCUCCCCAAUCCACU 24 6011

SCNNlA-2163 - GUGAUGGGAGAGGGCACU 18 6012

SCNNlA-2164 - GGUGAUGGGAGAGGGCACU 19 6013

SCNNlA-2165 - GGGUGAUGGGAGAGGGCACU 20 6014

SCNNlA-2166 - GGGGUGAUGGGAGAGGGCACU 21 6015

SCNNlA-2167 - AGGGGUGAUGGGAGAGGGCACU 22 6016

SCNNlA-2168 - CAGGGGUGAUGGGAGAGGGCACU 23 6017

SCNNlA-2169 - CCAGGGGUGAUGGGAGAGGGCACU 24 6018

SCNN1A-

- UGACCACAUUCCUGCACU 18

10361 14210

SCNN1A-

- GUGACCACAUUCCUGCACU 19

10362 14211

SCNN1A-

- AGUGACCACAUUCCUGCACU 20

10363 14212

SCNN1A-

- CAGUGACCACAUUCCUGCACU 21

10364 14213

SCNN1A-

- CCAGUGACCACAUUCCUGCACU 22

10365 14214

SCNN1A-

- GCCAGUGACCACAUUCCUGCACU 23

10366 14215

SCNN1A-

- AGCCAGUGACCACAUUCCUGCACU 24

10367 14216

SCNN1A- - AGGUGCUUUUCAGAACCU 18 14217

1482

5535.1 10368

SCNN1A-

- GAGGUGCUUUUCAGAACCU 19

10369 14218

SCNN1A-

- GGAGGUGCUUUUCAGAACCU 20

10370 14219

SCNN1A-

- GGGAGGUGCUUUUCAGAACCU 21

10371 14220

SCNN1A-

- AGGGAGGUGCUUUUCAGAACCU 22

10372 14221

SCNN1A-

- CAGGGAGGUGCUUUUCAGAACCU 23

10373 14222

SCNN1A-

- GCAGGGAGGUGCUUUUCAGAACCU 24

10374 14223

SCNN1A-

- UAUUUUGUUUUCUAACCU 18

10375 14224

SCNN1A-

- CUAUUUUGUUUUCUAACCU 19

10376 14225

SCNN1A-

- CCUAUUUUGUUUUCUAACCU 20

10377 14226

SCNN1A-

- UCCUAUUUUGUUUUCUAACCU 21

10378 14227

SCNN1A-

- CUCCUAUUUUGUUUUCUAACCU 22

10379 14228

SCNN1A-

- GCUCCUAUUUUGUUUUCUAACCU 23

10380 14229

SCNN1A-

- UGCUCCUAUUUUGUUUUCUAACCU 24

10381 14230

SCNN1A-

- UCCCAGUUCACCUGCCCU 18

10382 14231

SCNN1A-

- CUCCCAGUUCACCUGCCCU 19

10383 14232

SCNNlA-5736 - ACUCCCAGUUCACCUGCCCU 20 9585

SCNN1A-

- UACUCCCAGUUCACCUGCCCU 21

10384 14233

SCNN1A-

- GUACUCCCAGUUCACCUGCCCU 22

10385 14234

SCNN1A-

- AGUACUCCCAGUUCACCUGCCCU 23

10386 14235

SCNN1A-

- CAGUACUCCCAGUUCACCUGCCCU 24

10387 14236

SCNN1A-

- CUGACCUGUGGGUGCCCU 18

10388 14237

SCNN1A- - GCUGACCUGUGGGUGCCCU 19 14238

1483

5535.1 10389

SCNNlA-5274 - GGCUGACCUGUGGGUGCCCU 20 9123

SCNN1A-

- AGGCUGACCUGUGGGUGCCCU 21

10390 14239

SCNN1A-

- GAGGCUGACCUGUGGGUGCCCU 22

10391 14240

SCNN1A-

- UGAGGCUGACCUGUGGGUGCCCU 23

10392 14241

SCNN1A-

- GUGAGGCUGACCUGUGGGUGCCCU 24

10393 14242

SCNN1A-

- AGAAAACUGAUUUAUCCU 18

10394 14243

SCNN1A-

- CAGAAAACUGAUUUAUCCU 19

10395 14244

SCNNlA-6181 - UCAGAAAACUGAUUUAUCCU 20 10030

SCNN1A-

- CUCAGAAAACUGAUUUAUCCU 21

10396 14245

SCNN1A-

- CCUCAGAAAACUGAUUUAUCCU 22

10397 14246

SCNN1A-

- ACCUCAGAAAACUGAUUUAUCCU 23

10398 14247

SCNN1A-

- AACCUCAGAAAACUGAUUUAUCCU 24

10399 14248

SCNN1A-

- CACUCUGGGCUGCCUCCU 18

10400 14249

SCNN1A-

- GCACUCUGGGCUGCCUCCU 19

10401 14250

SCNN1A-

- UGCACUCUGGGCUGCCUCCU 20

10402 14251

SCNN1A-

- CUGCACUCUGGGCUGCCUCCU 21

10403 14252

SCNN1A-

- CCUGCACUCUGGGCUGCCUCCU 22

10404 14253

SCNN1A-

- UCCUGCACUCUGGGCUGCCUCCU 23

10405 14254

SCNN1A-

- UUCCUGCACUCUGGGCUGCCUCCU 24

10406 14255

SCNN1A-

- UCGGGAGCCCUCCUUCCU 18

10407 14256

SCNN1A-

- CUCGGGAGCCCUCCUUCCU 19

10408 14257

SCNN1A-

- CCUCGGGAGCCCUCCUUCCU 20

10409 14258

1484

5535.1 SCNN1A-

- CCCUCGGGAGCCCUCCUUCCU 21

10410 14259

SCNN1A-

- GCCCUCGGGAGCCCUCCUUCCU 22

10411 14260

SCNN1A-

- UGCCCUCGGGAGCCCUCCUUCCU 23

10412 14261

SCNN1A-

- CUGCCCUCGGGAGCCCUCCUUCCU 24

10413 14262

SCNN1A-

- GGGCCAGAGGCUGGAGCU 18

10414 14263

SCNN1A-

- AGGGCCAGAGGCUGGAGCU 19

10415 14264

SCNN1A-

- CAGGGCCAGAGGCUGGAGCU 20

10416 14265

SCNN1A-

- UCAGGGCCAGAGGCUGGAGCU 21

10417 14266

SCNN1A-

- GUCAGGGCCAGAGGCUGGAGCU 22

10418 14267

SCNN1A-

- GGUCAGGGCCAGAGGCUGGAGCU 23

10419 14268

SCNN1A-

- AGGUCAGGGCCAGAGGCUGGAGCU 24

10420 14269

SCNN1A-

- UGUGUUGCCCUCCUAGCU 18

10421 14270

SCNN1A-

- UUGUGUUGCCCUCCUAGCU 19

10422 14271

SCNN1A-

- CUUGUGUUGCCCUCCUAGCU 20

10423 14272

SCNN1A-

- CCUUGUGUUGCCCUCCUAGCU 21

10424 14273

SCNN1A-

- UCCUUGUGUUGCCCUCCUAGCU 22

10425 14274

SCNN1A-

- CUCCUUGUGUUGCCCUCCUAGCU 23

10426 14275

SCNN1A-

- UCUCCUUGUGUUGCCCUCCUAGCU 24

10427 14276

SCNN1A-

- GGCUCUUAUGUCUUAUCU 18

10428 14277

SCNN1A-

- UGGCUCUUAUGUCUUAUCU 19

10429 14278

SCNN1A-

- UUGGCUCUUAUGUCUUAUCU 20

10430 14279

SCNN1A- - CUUGGCUCUUAUGUCUUAUCU 21 14280

1485

5535.1 10431

SCNN1A-

- CCUUGGCUCUUAUGUCUUAUCU 22

10432 14281

SCNN1A-

- CCCUUGGCUCUUAUGUCUUAUCU 23

10433 14282

SCNN1A-

- GCCCUUGGCUCUUAUGUCUUAUCU 24

10434 14283

SCNN1A-

- CUCUUAUGUCUUAUCUCU 18

10435 14284

SCNN1A-

- GCUCUUAUGUCUUAUCUCU 19

10436 14285

SCNN1A-

- GGCUCUUAUGUCUUAUCUCU 20

10437 14286

SCNN1A-

- UGGCUCUUAUGUCUUAUCUCU 21

10438 14287

SCNN1A-

- UUGGCUCUUAUGUCUUAUCUCU 22

10439 14288

SCNN1A-

- CUUGGCUCUUAUGUCUUAUCUCU 23

10440 14289

SCNN1A-

- CCUUGGCUCUUAUGUCUUAUCUCU 24

10441 14290

SCNN1A-

- AGAGAUGACACCUUCUCU 18

10442 14291

SCNN1A-

- CAGAGAUGACACCUUCUCU 19

10443 14292

SCNNlA-5926 - GCAGAGAUGACACCUUCUCU 20 9775

SCNN1A-

- AGCAGAGAUGACACCUUCUCU 21

10444 14293

SCNN1A-

- CAGCAGAGAUGACACCUUCUCU 22

10445 14294

SCNN1A-

- UCAGCAGAGAUGACACCUUCUCU 23

10446 14295

SCNN1A-

- UUCAGCAGAGAUGACACCUUCUCU 24

10447 14296

SCNN1A-

- UGGAGUUUCUAGGGGUCU 18

10448 14297

SCNN1A-

- CUGGAGUUUCUAGGGGUCU 19

10449 14298

SCNN1A-

- ACUGGAGUUUCUAGGGGUCU 20

10450 14299

SCNN1A-

- GACUGGAGUUUCUAGGGGUCU 21

10451 14300

SCNN1A- - AGACUGGAGUUUCUAGGGGUCU 22 14301

1486

5535.1 10452

SCNN1A-

- GAGACUGGAGUUUCUAGGGGUCU 23

10453 14302

SCNN1A-

- GGAGACUGGAGUUUCUAGGGGUCU 24

10454 14303

SCNN1A-

- UCCCCCAUGAGUCUGUCU 18

10455 14304

SCNN1A-

- AUCCCCCAUGAGUCUGUCU 19

10456 14305

SCNN1A-

- GAUCCCCCAUGAGUCUGUCU 20

10457 14306

SCNN1A-

- CGAUCCCCCAUGAGUCUGUCU 21

10458 14307

SCNN1A-

- CCGAUCCCCCAUGAGUCUGUCU 22

10459 14308

SCNN1A-

- CCCGAUCCCCCAUGAGUCUGUCU 23

10460 14309

SCNN1A-

- CCCCGAUCCCCCAUGAGUCUGUCU 24

10461 14310

SCNN1A-

- GCAGAGAUGACACCUUCU 18

10462 14311

SCNN1A-

- AGCAGAGAUGACACCUUCU 19

10463 14312

SCNN1A-

- CAGCAGAGAUGACACCUUCU 20

10464 14313

SCNN1A-

- UCAGCAGAGAUGACACCUUCU 21

10465 14314

SCNN1A-

- UUCAGCAGAGAUGACACCUUCU 22

10466 14315

SCNN1A-

- AUUCAGCAGAGAUGACACCUUCU 23

10467 14316

SCNN1A-

- GAUUCAGCAGAGAUGACACCUUCU 24

10468 14317

SCNN1A-

- CAGAGGAGAGGCCGUUCU 18

10469 14318

SCNN1A-

- GCAGAGGAGAGGCCGUUCU 19

10470 14319

SCNNlA-5750 - AGCAGAGGAGAGGCCGUUCU 20 9599

SCNN1A-

- AAGCAGAGGAGAGGCCGUUCU 21

10471 14320

SCNN1A-

- GAAGCAGAGGAGAGGCCGUUCU 22

10472 14321

SCNN1A- - GGAAGCAGAGGAGAGGCCGUUCU 23 14322

1487

5535.1 10473

SCNN1A-

- GGGAAGCAGAGGAGAGGCCGUUCU 24

10474 14323

SCNN1A-

- CCUUUUGCUGCAUUAAGU 18

10475 14324

SCNN1A-

- UCCUUUUGCUGCAUUAAGU 19

10476 14325

SCNN1A-

- AUCCUUUUGCUGCAUUAAGU 20

10477 14326

SCNN1A-

- UAUCCUUUUGCUGCAUUAAGU 21

10478 14327

SCNN1A-

- UUAUCCUUUUGCUGCAUUAAGU 22

10479 14328

SCNN1A-

- CUUAUCCUUUUGCUGCAUUAAGU 23

10480 14329

SCNN1A-

- CCUUAUCCUUUUGCUGCAUUAAGU 24

10481 14330

SCNN1A-

- UGGGAUAUGUGGGGCAGU 18

10482 14331

SCNN1A-

- CUGGGAUAUGUGGGGCAGU 19

10483 14332

SCNNlA-5753 - UCUGGGAUAUGUGGGGCAGU 20 9602

SCNN1A-

- CUCUGGGAUAUGUGGGGCAGU 21

10484 14333

SCNN1A-

- UCUCUGGGAUAUGUGGGGCAGU 22

10485 14334

SCNN1A-

- GUCUCUGGGAUAUGUGGGGCAGU 23

10486 14335

SCNN1A-

- GGUCUCUGGGAUAUGUGGGGCAGU 24

10487 14336

SCNN1A-

- GAGCUGAGGGCCUAGAGU 18

10488 14337

SCNN1A-

- GGAGCUGAGGGCCUAGAGU 19

10489 14338

SCNN1A-

- UGGAGCUGAGGGCCUAGAGU 20

10490 14339

SCNN1A-

- CUGGAGCUGAGGGCCUAGAGU 21

10491 14340

SCNN1A-

- GCUGGAGCUGAGGGCCUAGAGU 22

10492 14341

SCNN1A-

- GGCUGGAGCUGAGGGCCUAGAGU 23

10493 14342

SCNN1A- - AGGCUGGAGCUGAGGGCCUAGAGU 24 14343

1488

5535.1 10494

SCNN1A-

- GAGGAGGGAGGGAGGAGU 18

10495 14344

SCNN1A-

- GGAGGAGGGAGGGAGGAGU 19

10496 14345

SCNNlA-6187 - UGGAGGAGGGAGGGAGGAGU 20 10036

SCNN1A-

- GUGGAGGAGGGAGGGAGGAGU 21

10497 14346

SCNN1A-

- GGUGGAGGAGGGAGGGAGGAGU 22

10498 14347

SCNN1A-

- AGGUGGAGGAGGGAGGGAGGAGU 23

10499 14348

SCNN1A-

- AAGGUGGAGGAGGGAGGGAGGAGU 24

10500 14349

SCNN1A-

- GGCAGAUAGAGAGGGAGU 18

10501 14350

SCNN1A-

- AGGCAGAUAGAGAGGGAGU 19

10502 14351

SCNN1A-

- AAGGCAGAUAGAGAGGGAGU 20

10503 14352

SCNN1A-

- GAAGGCAGAUAGAGAGGGAGU 21

10504 14353

SCNN1A-

- AGAAGGCAGAUAGAGAGGGAGU 22

10505 14354

SCNN1A-

- CAGAAGGCAGAUAGAGAGGGAGU 23

10506 14355

SCNN1A-

- ACAGAAGGCAGAUAGAGAGGGAGU 24

10507 14356

SCNN1A-

- CAGCCGCAACCUGGGAGU 18

10508 14357

SCNN1A-

- CCAGCCGCAACCUGGGAGU 19

10509 14358

SCNNlA-5754 - UCCAGCCGCAACCUGGGAGU 20 9603

SCNN1A-

- GUCCAGCCGCAACCUGGGAGU 21

10510 14359

SCNN1A-

- AGUCCAGCCGCAACCUGGGAGU 22

10511 14360

SCNN1A-

- CAGUCCAGCCGCAACCUGGGAGU 23

10512 14361

SCNN1A-

- CCAGUCCAGCCGCAACCUGGGAGU 24

10513 14362

SCNN1A-

- CGGGCUCUGUGUGGGAGU 18

10514 14363

1489

5535.1 SCNN1A-

- ACGGGCUCUGUGUGGGAGU 19

10515 14364

SCNN1A-

- CACGGGCUCUGUGUGGGAGU 20

10516 14365

SCNN1A-

- CCACGGGCUCUGUGUGGGAGU 21

10517 14366

SCNN1A-

- UCCACGGGCUCUGUGUGGGAGU 22

10518 14367

SCNN1A-

- AUCCACGGGCUCUGUGUGGGAGU 23

10519 14368

SCNN1A-

- AAUCCACGGGCUCUGUGUGGGAGU 24

10520 14369

SCNN1A-

- GCCUCCUGUGGGGCCCGU 18

10521 14370

SCNN1A-

- UGCCUCCUGUGGGGCCCGU 19

10522 14371

SCNN1A-

- CUGCCUCCUGUGGGGCCCGU 20

10523 14372

SCNN1A-

- GCUGCCUCCUGUGGGGCCCGU 21

10524 14373

SCNN1A-

- GGCUGCCUCCUGUGGGGCCCGU 22

10525 14374

SCNN1A-

- GGGCUGCCUCCUGUGGGGCCCGU 23

10526 14375

SCNN1A-

- UGGGCUGCCUCCUGUGGGGCCCGU 24

10527 14376

SCNN1A-

- CCCGGGUCUGGACAAGGU 18

10528 14377

SCNN1A-

- UCCCGGGUCUGGACAAGGU 19

10529 14378

SCNNlA-5755 - CUCCCGGGUCUGGACAAGGU 20 9604

SCNN1A-

- CCUCCCGGGUCUGGACAAGGU 21

10530 14379

SCNN1A-

- CCCUCCCGGGUCUGGACAAGGU 22

10531 14380

SCNN1A-

- CCCCUCCCGGGUCUGGACAAGGU 23

10532 14381

SCNN1A-

- GCCCCUCCCGGGUCUGGACAAGGU 24

10533 14382

SCNN1A-

- CCGCUGCACCUGUCAGGU 18

10534 14383

SCNN1A-

- GCCGCUGCACCUGUCAGGU 19

10535 14384

1490

5535.1 SCNN1A-

- GGCCGCUGCACCUGUCAGGU 20

10536 14385

SCNN1A-

- AGGCCGCUGCACCUGUCAGGU 21

10537 14386

SCNN1A-

- CAGGCCGCUGCACCUGUCAGGU 22

10538 14387

SCNN1A-

- CCAGGCCGCUGCACCUGUCAGGU 23

10539 14388

SCNN1A-

- GCCAGGCCGCUGCACCUGUCAGGU 24

10540 14389

SCNN1A-

- CAGGACACAGCUCGAGGU 18

10541 14390

SCNN1A-

- UCAGGACACAGCUCGAGGU 19

10542 14391

SCNN1A-

- AUCAGGACACAGCUCGAGGU 20

10543 14392

SCNN1A-

- AAUCAGGACACAGCUCGAGGU 21

10544 14393

SCNN1A-

- GAAUCAGGACACAGCUCGAGGU 22

10545 14394

SCNN1A-

- AGAAUCAGGACACAGCUCGAGGU 23

10546 14395

SCNN1A-

- CAG AAU CAGG ACACAG CU CG AGG U 24

10547 14396

SCNN1A-

- CCUGGGCCCCUCCCGGGU 18

10548 14397

SCNN1A-

- ACCUGGGCCCCUCCCGGGU 19

10549 14398

SCNN1A-

- CACCUGGGCCCCUCCCGGGU 20

10550 14399

SCNN1A-

- UCACCUGGGCCCCUCCCGGGU 21

10551 14400

SCNN1A-

- UUCACCUGGGCCCCUCCCGGGU 22

10552 14401

SCNN1A-

- CUUCACCUGGGCCCCUCCCGGGU 23

10553 14402

SCNN1A-

- GCUUCACCUGGGCCCCUCCCGGGU 24

10554 14403

SCNNlA-2176 - UAAGCAAGGGAACCUGGU 18 6025

SCNNlA-2177 - GUAAGCAAGGGAACCUGGU 19 6026

SCNNlA-2178 - GGUAAGCAAGGGAACCUGGU 20 6027

SCNNlA-2179 - AGGUAAGCAAGGGAACCUGGU 21 6028

SCNNlA-2180 - AAGGUAAGCAAGGGAACCUGGU 22 6029

1491

5535.1 SCNNlA-2181 - C A AG G U A AG C A AG GGAACCUGGU 23 6030

SCNNlA-2182 - UCAAGGUAAGCAAGGGAACCUGGU 24 6031

SCNN1A-

- GAGGACCAUGCCCAAUGU 18

10555 14404

SCNN1A-

- GGAGGACCAUGCCCAAUGU 19

10556 14405

SCNN1A-

- GGGAGGACCAUGCCCAAUGU 20

10557 14406

SCNN1A-

- AGGGAGGACCAUGCCCAAUGU 21

10558 14407

SCNN1A-

- CAGGGAGGACCAUGCCCAAUGU 22

10559 14408

SCNN1A-

- GCAGGGAGGACCAUGCCCAAUGU 23

10560 14409

SCNN1A-

- UGCAGGGAGGACCAUGCCCAAUGU 24

10561 14410

SCNN1A-

- CGAAUCCACGGGCUCUGU 18

10562 14411

SCNN1A-

- ACGAAUCCACGGGCUCUGU 19

10563 14412

SCNN1A-

- GACGAAUCCACGGGCUCUGU 20

10564 14413

SCNN1A-

- AGACGAAUCCACGGGCUCUGU 21

10565 14414

SCNN1A-

- CAGACGAAUCCACGGGCUCUGU 22

10566 14415

SCNN1A-

- GCAGACGAAUCCACGGGCUCUGU 23

10567 14416

SCNN1A-

- AGCAGACGAAUCCACGGGCUCUGU 24

10568 14417

SCNN1A-

- UGAGAUCUGCACUUUUGU 18

10569 14418

SCNN1A-

- CUGAGAUCUGCACUUUUGU 19

10570 14419

SCNN1A-

- UCUGAGAUCUGCACUUUUGU 20

10571 14420

SCNN1A-

- AUCUGAGAUCUGCACUUUUGU 21

10572 14421

SCNN1A-

- AAUCUGAGAUCUGCACUUUUGU 22

10573 14422

SCNN1A-

- AAAUCUGAGAUCUGCACUUUUGU 23

10574 14423

SCNN1A- - GAAAUCUGAGAUCUGCACUUUUGU 24 14424

1492

5535.1 10575

SCNN1A-

- UAAGUUUGGAAAGAGAUU 18

10576 14425

SCNN1A-

- UUAAGUUUGGAAAGAGAUU 19

10577 14426

SCNN1A-

- AU U AAG U U UGG AAAG AG AU U 20

10578 14427

SCNN1A-

- CAU U AAG U U UGG AAAG AG AU U 21

10579 14428

SCNN1A-

- GCAU U AAG U U UGG AAAG AG AU U 22

10580 14429

SCNN1A-

- UG CAU U AAG U U UGG AAAG AG AU U 23

10581 14430

SCNN1A-

- CUGCAUUAAGUUUGGAAAGAGAUU 24

10582 14431

SCNN1A-

- GAAAACUGAUUUAUCCUU 18

10583 14432

SCNN1A-

- AGAAAACUGAUUUAUCCUU 19

10584 14433

SCNNlA-6189 - CAGAAAACUGAUUUAUCCUU 20 10038

SCNN1A-

- UCAGAAAACUGAUUUAUCCUU 21

10585 14434

SCNN1A-

- CUCAGAAAACUGAUUUAUCCUU 22

10586 14435

SCNN1A-

- CCUCAGAAAACUGAUUUAUCCUU 23

10587 14436

SCNN1A-

- ACCUCAGAAAACUGAUUUAUCCUU 24

10588 14437

SCNN1A-

- CGGGAGCCCUCCUUCCUU 18

10589 14438

SCNN1A-

- UCGGGAGCCCUCCUUCCUU 19

10590 14439

SCNNlA-5770 - CUCGGGAGCCCUCCUUCCUU 20 9619

SCNN1A-

- CCUCGGGAGCCCUCCUUCCUU 21

10591 14440

SCNN1A-

- CCCUCGGGAGCCCUCCUUCCUU 22

10592 14441

SCNN1A-

- GCCCUCGGGAGCCCUCCUUCCUU 23

10593 14442

SCNN1A-

- UGCCCUCGGGAGCCCUCCUUCCUU 24

10594 14443

SCNN1A-

- GCCUUUGUCUGCUGGCUU 18

10595 14444

1493

5535.1 SCNN1A-

- GGCCUUUGUCUGCUGGCUU 19

10596 14445

SCNN1A-

- GGGCCUUUGUCUGCUGGCUU 20

10597 14446

SCNN1A-

- UGGGCCUUUGUCUGCUGGCUU 21

10598 14447

SCNN1A-

- CUGGGCCUUUGUCUGCUGGCUU 22

10599 14448

SCNN1A-

- GCUGGGCCUUUGUCUGCUGGCUU 23

10600 14449

SCNN1A-

- GGCUGGGCCUUUGUCUGCUGGCUU 24

10601 14450

SCNN1A-

- CUUUUGCUGCAUUAAGUU 18

10602 14451

SCNN1A-

- CCUUUUGCUGCAUUAAGUU 19

10603 14452

SCNNlA-5771 - UCCUUUUGCUGCAUUAAGUU 20 9620

SCNN1A-

- AUCCUUUUGCUGCAUUAAGUU 21

10604 14453

SCNN1A-

- UAUCCUUUUGCUGCAUUAAGUU 22

10605 14454

SCNN1A-

- UUAUCCUUUUGCUGCAUUAAGUU 23

10606 14455

SCNN1A-

- CUUAUCCUUUUGCUGCAUUAAGUU 24

10607 14456

SCNN1A-

- AAGUUUGGAAAGAGAUUU 18

10608 14457

SCNN1A-

- UAAGUUUGGAAAGAGAUUU 19

10609 14458

SCNNlA-5773 - UUAAGUUUGGAAAGAGAUUU 20 9622

SCNN1A-

- AU U AAG U U UGG AAAG AG AU U U 21

10610 14459

SCNN1A-

- CAU U AAG U U UGG AAAG AG AU U U 22

10611 14460

SCNN1A-

- GCAU U AAG U U UGG AAAG AG AU U U 23

10612 14461

SCNN1A-

- UG CAU U AAG U U UGG AAAG AG AU U U 24

10613 14462

SCNN1A-

- GACACCGGCUUUCACUUU 18

10614 14463

SCNN1A-

- UGACACCGGCUUUCACUUU 19

10615 14464

SCNN1A- - UUGACACCGGCUUUCACUUU 20 14465

1494

5535.1 10616

SCNN1A-

- GUUGACACCGGCUUUCACUUU 21

10617 14466

SCNN1A-

- GGUUGACACCGGCUUUCACUUU 22

10618 14467

SCNN1A-

- UGGUUGACACCGGCUUUCACUUU 23

10619 14468

SCNN1A-

- CUGGUUGACACCGGCUUUCACUUU 24

10620 14469

SCNN1A-

- AGGCAGGGAGGUGCUUUU 18

10621 14470

SCNN1A-

- AAGGCAGGGAGGUGCUUUU 19

10622 14471

SCNN1A-

- AAAGGCAGGGAGGUGCUUUU 20

10623 14472

SCNN1A-

- AAAAGGCAGGGAGGUGCUUUU 21

10624 14473

SCNN1A-

- GAAAAGGCAGGGAGGUGCUUUU 22

10625 14474

SCNN1A-

- AGAAAAGGCAGGGAGGUGCUUUU 23

10626 14475

SCNN1A-

- UAGAAAAGGCAGGGAGGUGCUUUU 24

10627 14476

Table 47E provides exemplary targeting domains for knocking down the SCNNIA gene selected according to the fifth tier parameters. The targeting domains bind within the additional 500 bp (e.g., upstream or downstream) of a transcription start site (TSS), e.g., extending to lkb upstream and downstream of a TSS, starts with a 5'G and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through co Any of the targeting domains in the table can be used with a S. Aureus eiCas9 molecule or eiCas9 fusion protein (e.g., an eiCas9 fused to a transcription repressor domain) to alter the SCNNIA gene (e.g., reduce or eliminate SCNNIA gene expression, SCNNIA protein function, or the level of SCNNIA protein). One or more gRNA may be used to target an eiCas9 to the promoter region of the SCNNIA genemplementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 47E

1495

5535.1 5th Tier

Target Site

gRNA Name DNA Strand Targeting Domain

Length Seq ID

SCNN1A-

+ GCCUGGUCUGGGCUGAGCCA 20

10628 14477

SCNNlA-1302 + GGUUGAUGUUGAGGCUGA 18 5151

SCNNlA-42 + GAGGUUGAUGUUGAGGCUGA 20 519

SCNNlA-1303 + GUUGAGGUUGAUGUUGAGGCUGA 23 5152

SCNN1A-

+ GUGAGCUCUACCUGGGAC 18

10629 14478

SCNN1A-

+ GCAGUGAGCUCUACCUGGGAC 21

10630 14479

SCNNlA-1417 + GUUCCCCUUCAUGAGCCC 18 5266

SCNNlA-1420 + GCUUGUUCCCCUUCAUGAGCCC 22 5269

SCNNlA-1427 + GCACACCAGGCGGAUGGCGCC 21 5276

SCNNlA-1429 + GAGCACACCAGGCGGAUGGCGCC 23 5278

SCNNlA-1430 + GGAGCACACCAGGCGGAUGGCGCC 24 5279

SCNN1A-

+ GAUCAUGCACUAUCCUCUAGGC 22

10631 14480

SCNN1A-

+ GGAUCAUGCACUAUCCUCUAGGC 23

10632 14481

SCNNlA-1316 + GUGCUGGGAGCACACCAG 18 5165

SCNNlA-1317 + GUUGUGCUGGGAGCACACCAG 21 5166

SCNNlA-1318 + GGUUGUGCUGGGAGCACACCAG 22 5167

SCNNlA-1319 + GCGGUUGUGCUGGGAGCACACCAG 24 5168

SCNNlA-1320 + GUACUCUCCGAAAAGCAGG 19 5169

SCNNlA-1321 + GAAGUACUCUCCGAAAAGCAGG 22 5170

SCNN1A-

+ GUGACCCUGCCACGUCCUG 19

10633 14482

SCNN1A-

+ GGUGACCCUGCCACGUCCUG 20

10634 14483

SCNN1A-

+ GUGGUGACCCUGCCACGUCCUG 22

10635 14484

SCNN1A-

+ GGUGGUGACCCUGCCACGUCCUG 23

10636 14485

SCNN1A-

+ GGGUGGUGACCCUGCCACGUCCUG 24

10637 14486

SCNN1A-

+ GCCACGUCCUGCCGGGUAU 19

10638 14487

SCNNlA-1326 + GAGGGACUAACCGACCUGU 19 5175

SCNNlA-1327 + GCAGAGGGACUAACCGACCUGU 22 5176

SCNNlA-1328 + GGCAGAGGGACUAACCGACCUGU 23 5177

SCNNlA-1329 + GGGCAGAGGGACUAACCGACCUGU 24 5178

1496

5535.1 SCNNlA-1330 + GCGGGGAAGACGAGCUUGU 19 5179

SCNNlA-1331 + GACUAACCGACCUGUAGGGAUU 22 5180

SCNNlA-1332 + GGACUAACCGACCUGUAGGGAUU 23 5181

SCNNlA-1333 + GGGACUAACCGACCUGUAGGGAUU 24 5182

SCNNlA-1334 - GCGGAGGAGGAGGCCCUGA 19 5183

SCNNlA-189 - GGCGGAGGAGGAGGCCCUGA 20 819

SCNN1A-

- GCUGCUGUACUCCAGCCUA 19

10639 14488

SCNN1A-

- GUUCUAGCCCGCUCCAGGUC 20

10640 14489

SCNN1A-

- GCCUGUUCUAGCCCGCUCCAGGUC 24

10641 14490

SCNN1A-

- GCGCCUGGAAGGGUGGUC 18

10642 14491

SCNN1A-

- GCCUGCGCCUGGAAGGGUGGUC 22

10643 14492

SCNN1A-

- GUGCCUGCGCCUGGAAGGGUGGUC 24

10644 14493

SCNNlA-197 - GCAAUUCGGCCUGCUUUUCG 20 826

SCNNlA-1337 - GGCAAUUCGGCCUGCUUUUCG 21 5186

SCNN1A-

- GCAGGCAGAGCCUCAGACCU 20

10645 14494

SCNN1A-

- GGCAGGCAGAGCCUCAGACCU 21

10646 14495

SCNN1A-

- GGGCAGGCAGAGCCUCAGACCU 22

10647 14496

SCNNlA-1338 - GCUCCUACCGAGAGCUCU 18 5187

Table 47F provides exemplary targeting domains for knocking down the SCNNIA gene selected according to the six tier parameters. The targeting domains bind within the additional 500 bp (e.g., upstream or downstream) of a transcription start site (TSS), e.g., extending to lkb upstream and downstream of a TSS and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. Aureus eiCas9 molecule or eiCas9 fusion protein (e.g., an eiCas9 fused to a transcription repressor domain) to alter the SCNNIA gene (e.g., reduce or eliminate SCNNIA gene expression, SCNNIA protein function, or the level of SCNNIA protein). One or more gRNA may be used to target an eiCas9 to the promoter region of the SCNNIA gene.

Table 47F

1497

5535.1 6th Tier

Target Site

gRNA Name DNA Strand Targeting Domain

Length Seq ID

SCNN1A-

+ CUGGUCUGGGCUGAGCCA 18

10648 14497

SCNN1A-

+ CCUGGUCUGGGCUGAGCCA 19

10649 14498

SCNN1A-

+ UGCCUGGUCUGGGCUGAGCCA 21

10650 14499

SCNN1A-

+ AUGCCUGGUCUGGGCUGAGCCA 22

10651 14500

SCNN1A-

+ AAUGCCUGGUCUGGGCUGAGCCA 23

10652 14501

SCNN1A-

+ CAAUGCCUGGUCUGGGCUGAGCCA 24

10653 14502

SCNN1A-

+ UCUUAUUUAUCUUAGAGA 18

10654 14503

SCNN1A-

+ UUCUUAUUUAUCUUAGAGA 19

10655 14504

SCNN1A-

+ UUUCUUAUUUAUCUUAGAGA 20

10656 14505

SCNN1A-

+ UUUUCUUAUUUAUCUUAGAGA 21

10657 14506

SCNN1A-

+ AUUUUCUUAUUUAUCUUAGAGA 22

10658 14507

SCNN1A-

+ UAUUUUCUUAUUUAUCUUAGAGA 23

10659 14508

SCNN1A-

+ UUAUUUUCUUAUUUAUCUUAGAGA 24

10660 14509

SCNNlA-1340 + AGGUUGAUGUUGAGGCUGA 19 5189

SCNNlA-1341 + UGAGGUUGAUGUUGAGGCUGA 21 5190

SCNNlA-1342 + UUGAGGUUGAUGUUGAGGCUGA 22 5191

SCNNlA-1343 + AGUUGAGGUUGAUGUUGAGGCUGA 24

5192

SCNN1A-

+ AGUGAGCUCUACCUGGGAC 19

10661 14510

SCNNlA-6306 + CAGUGAGCUCUACCUGGGAC 20 10155

SCNN1A-

+ AGCAGUGAGCUCUACCUGGGAC 22

10662 14511

SCNN1A-

+ CAGCAGUGAGCUCUACCUGGGAC 23

10663 14512

SCNN1A-

+ CCAGCAGUGAGCUCUACCUGGGAC 24

10664 14513

1498

5535.1 SCNNlA-1418 + UGUUCCCCUUCAUGAGCCC 19 5267

SCNNlA-72 + UUGUUCCCCUUCAUGAGCCC 20 599

SCNNlA-1419 + CUUGUUCCCCUUCAUGAGCCC 21 5268

SCNNlA-1423 + CGCUUGUUCCCCUUCAUGAGCCC 23 5272

SCNNlA-1424 + ACGCUUGUUCCCCUUCAUGAGCCC 24 5273

SCNNlA-1425 + CACCAGGCGGAUGGCGCC 18 5274

SCNNlA-1426 + ACACCAGGCGGAUGGCGCC 19 5275

SCNNlA-223 + CACACCAGGCGGAUGGCGCC 20 846

SCNNlA-1428 + AGCACACCAGGCGGAUGGCGCC 22 5277

SCNN1A-

+ AUGCACUAUCCUCUAGGC 18

10665 14514

SCNN1A-

+ CAUGCACUAUCCUCUAGGC 19

10666 14515

SCNNlA-6323 + UCAUGCACUAUCCUCUAGGC 20 10172

SCNN1A-

+ AUCAUGCACUAUCCUCUAGGC 21

10667 14516

SCNN1A-

+ AGGAUCAUGCACUAUCCUCUAGGC 24

10668 14517

SCNNlA-1371 + UGUGCUGGGAGCACACCAG 19 5220

SCNNlA-224 + UUGUGCUGGGAGCACACCAG 20 847

SCNNlA-1372 + CGGUUGUGCUGGGAGCACACCAG 23 5221

SCNNlA-1373 + UACUCUCCGAAAAGCAGG 18 5222

SCNNlA-230 + AGUACUCUCCGAAAAGCAGG 20 851

SCNNlA-1374 + AAGUACUCUCCGAAAAGCAGG 21 5223

SCNNlA-1375 + UGAAGUACUCUCCGAAAAGCAGG 23 5224

SCNNlA-1376 + CUGAAGUACUCUCCGAAAAGCAGG 24 5225

SCNN1A-

+ UGACCCUGCCACGUCCUG 18

10669 14518

SCNN1A-

+ UGGUGACCCUGCCACGUCCUG 21

10670 14519

SCNN1A-

+ CCACGUCCUGCCGGGUAU 18

10671 14520

SCNNlA-6350 + UGCCACGUCCUGCCGGGUAU 20 10199

SCNN1A-

+ CUGCCACGUCCUGCCGGGUAU 21

10672 14521

SCNN1A-

+ CCUGCCACGUCCUGCCGGGUAU 22

10673 14522

SCNN1A-

+ CCCUGCCACGUCCUGCCGGGUAU 23

10674 14523

SCNN1A-

+ ACCCUGCCACGUCCUGCCGGGUAU 24

10675 14524

SCNNlA-1380 + AGGGACUAACCGACCUGU 18 5229

SCNNlA-424 + AGAGGGACUAACCGACCUGU 20 4273

1499

5535.1 SCNNlA-1381 + CAGAGGGACUAACCGACCUGU 21 5230

SCNNlA-1382 + CGGGGAAGACGAGCUUGU 18 5231

SCNNlA-237 + UGCGGGGAAGACGAGCUUGU 20 857

SCNNlA-1383 + CUGCGGGGAAGACGAGCUUGU 21 5232

SCNNlA-1384 + ACUGCGGGGAAGACGAGCUUGU 22 5233

SCNNlA-1385 + CACUGCGGGGAAGACGAGCUUGU 23 5234

SCNNlA-1386 + UCACUGCGGGGAAGACGAGCUUGU 24 5235

SCNNlA-1387 + AACCGACCUGUAGGGAUU 18 5236

SCNNlA-1388 + UAACCGACCUGUAGGGAUU 19 5237

SCNNlA-1389 + CUAACCGACCUGUAGGGAUU 20 5238

SCNNlA-1390 + ACUAACCGACCUGUAGGGAUU 21 5239

SCNNlA-1391 - CGGAGGAGGAGGCCCUGA 18 5240

SCNNlA-1433 - CGGCGGAGGAGGAGGCCCUGA 21 5282

SCNNlA-1434 - ACGGCGGAGGAGGAGGCCCUGA 22 5283

SCNNlA-1435 - CACGGCGGAGGAGGAGGCCCUGA 23 5284

SCNNlA-1436 - CCACGGCGGAGGAGGAGGCCCUGA 24 5285

SCNN1A-

- CUGCUGUACUCCAGCCUA 18

10676 14525

SCNN1A-

- UGCUGCUGUACUCCAGCCUA 20

10677 14526

SCNN1A-

- AUGCUGCUGUACUCCAGCCUA 21

10678 14527

SCNN1A-

- CAUGCUGCUGUACUCCAGCCUA 22

10679 14528

SCNN1A-

- UCAUGCUGCUGUACUCCAGCCUA 23

10680 14529

SCNN1A-

- AUCAUGCUGCUGUACUCCAGCCUA 24

10681 14530

SCNN1A-

- UCUAGCCCGCUCCAGGUC 18

10682 14531

SCNN1A-

- UUCUAGCCCGCUCCAGGUC 19

10683 14532

SCNN1A-

- UGUUCUAGCCCGCUCCAGGUC 21

10684 14533

SCNN1A-

- CUGUUCUAGCCCGCUCCAGGUC 22

10685 14534

SCNN1A-

- CCUGUUCUAGCCCGCUCCAGGUC 23

10686 14535

SCNN1A-

- UGCGCCUGGAAGGGUGGUC 19

10687 14536

SCNN1A-

- CUGCGCCUGGAAGGGUGGUC 20

10688 14537

SCNN1A- - CCUGCGCCUGGAAGGGUGGUC 21 14538

1500

5535.1 10689

SCNN1A-

- UGCCUGCGCCUGGAAGGGUGGUC 23

10690 14539

SCNNlA-1395 - AAUUCGGCCUGCUUUUCG 18 5244

SCNNlA-1396 - CAAUUCGGCCUGCUUUUCG 19 5245

SCNNlA-1397 - UGGCAAUUCGGCCUGCUUUUCG 22 5246

SCNNlA-1398 - CUGGCAAUUCGGCCUGCUUUUCG 23 5247

SCNNlA-1399 - ACUGGCAAUUCGGCCUGCUUUUCG 24 5248

SCNN1A-

- CCUGGUGCCUGCGCCUGG 18

10691 14540

SCNN1A-

- CCCUGGUGCCUGCGCCUGG 19

10692 14541

SCNN1A-

- UCCCUGGUGCCUGCGCCUGG 20

10693 14542

SCNN1A-

- UUCCCUGGUGCCUGCGCCUGG 21

10694 14543

SCNN1A-

- CUUCCCUGGUGCCUGCGCCUGG 22

10695 14544

SCNN1A-

- CCUUCCCUGGUGCCUGCGCCUGG 23

10696 14545

SCNN1A-

- CCCUUCCCUGGUGCCUGCGCCUGG 24

10697 14546

SCNN1A-

- AUACCCGGCAGGACGUGG 18

10698 14547

SCNN1A-

- CAUACCCGGCAGGACGUGG 19

10699 14548

SCNN1A-

- CCAUACCCGGCAGGACGUGG 20

10700 14549

SCNN1A-

- CCCAUACCCGGCAGGACGUGG 21

10701 14550

SCNN1A-

- UCCCAUACCCGGCAGGACGUGG 22

10702 14551

SCNN1A-

- CUCCCAUACCCGGCAGGACGUGG 23

10703 14552

SCNN1A-

- ACUCCCAUACCCGGCAGGACGUGG 24

10704 14553

SCNN1A-

- AGGCAGAGCCUCAGACCU 18

10705 14554

SCNN1A-

- CAGGCAGAGCCUCAGACCU 19

10706 14555

SCNN1A-

- UGGGCAGGCAGAGCCUCAGACCU 23

10707 14556

SCNN1A- - CUGGGCAGGCAGAGCCUCAGACCU 24 14557

1501

5535.1 10708

SCNNlA-1400 - CGCUCCUACCGAGAGCUCU 19 5249

SCNNlA-192 - CCGCUCCUACCGAGAGCUCU 20 822

SCNNlA-1401 - ACCGCUCCUACCGAGAGCUCU 21 5250

SCNNlA-1402 - CACCGCUCCUACCGAGAGCUCU 22 5251

SCNNlA-1403 - CCACCGCUCCUACCGAGAGCUCU 23 5252

SCNNlA-1404 - UCCACCGCUCCUACCGAGAGCUCU 24 5253

Table 47G provides exemplary targeting domains for knocking down the SCNNIA gene selected according to the seven tier parameters. The targeting domains bind within the additional 500 bp (e.g., upstream or downstream) of a transcription start site (TSS), e.g., extending to lkb upstream and downstream of a TSS and PAM is NNGRRV. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. Aureus eiCas9 molecule or eiCas9 fusion protein (e.g., an eiCas9 fused to a transcription repressor domain) to alter the SCNNIA gene (e.g., reduce or eliminate SCNNIA gene expression, SCNNIA protein function, or the level of SCNNIA protein). One or more gRNA may be used to target an eiCas9 to the promoter region of the SCNNIA gene.

Table 47G

1502

5535.1 SCNN1A-

+ CUUCCUUUCCCUCCCCAAA 19

10717 14566

SCNNlA-6279 + CCUUCCUUUCCCUCCCCAAA 20 10128

SCNN1A-

+ CCCUUCCUUUCCCUCCCCAAA 21

10718 14567

SCNN1A-

+ CCCCUUCCUUUCCCUCCCCAAA 22

10719 14568

SCNN1A-

+ UCCCCUUCCUUUCCCUCCCCAAA 23

10720 14569

SCNN1A-

+ GUCCCCUUCCUUUCCCUCCCCAAA 24

10721 14570

SCNN1A-

+ CUUCCUUUCCCUCCCCAA 18

10722 14571

SCNN1A-

+ CCUUCCUUUCCCUCCCCAA 19

10723 14572

SCNNlA-6281 + CCCUUCCUUUCCCUCCCCAA 20 10130

SCNN1A-

+ CCCCUUCCUUUCCCUCCCCAA 21

10724 14573

SCNN1A-

+ UCCCCUUCCUUUCCCUCCCCAA 22

10725 14574

SCNN1A-

+ GUCCCCUUCCUUUCCCUCCCCAA 23

10726 14575

SCNN1A-

+ AGUCCCCUUCCUUUCCCUCCCCAA 24

10727 14576

SCNN1A-

+ UUCCAGGCGCAGGCACCA 18

10728 14577

SCNN1A-

+ CUUCCAGGCGCAGGCACCA 19

10729 14578

SCNNlA-6290 + CCUUCCAGGCGCAGGCACCA 20 10139

SCNN1A-

+ CCCUUCCAGGCGCAGGCACCA 21

10730 14579

SCNN1A-

+ ACCCUUCCAGGCGCAGGCACCA 22

10731 14580

SCNN1A-

+ CACCCUUCCAGGCGCAGGCACCA 23

10732 14581

SCNN1A-

+ CCACCCUUCCAGGCGCAGGCACCA 24

10733 14582

SCNN1A-

+ CCUUCCUUUCCCUCCCCA 18

10734 14583

SCNN1A-

+ CCCUUCCUUUCCCUCCCCA 19

10735 14584

SCNN1A-

+ CCCCUUCCUUUCCCUCCCCA 20

10736 14585

1503

5535.1 SCNN1A-

+ UCCCCUUCCUUUCCCUCCCCA 21

10737 14586

SCNN1A-

+ GUCCCCUUCCUUUCCCUCCCCA 22

10738 14587

SCNN1A-

+ AGUCCCCUUCCUUUCCCUCCCCA 23

10739 14588

SCNN1A-

+ UAGUCCCCUUCCUUUCCCUCCCCA 24

10740 14589

SCNN1A-

+ UGAGGCUCUGCCUGCCCA 18

10741 14590

SCNN1A-

+ CUGAGGCUCUGCCUGCCCA 19

10742 14591

SCNN1A-

+ UCUGAGGCUCUGCCUGCCCA 20

10743 14592

SCNN1A-

+ GUCUGAGGCUCUGCCUGCCCA 21

10744 14593

SCNN1A-

+ GGUCUGAGGCUCUGCCUGCCCA 22

10745 14594

SCNN1A-

+ AGGUCUGAGGCUCUGCCUGCCCA 23

10746 14595

SCNN1A-

+ CAGGUCUGAGGCUCUGCCUGCCCA 24

10747 14596

SCNN1A-

+ GGCACCAGGGAAGGGGCA 18

10748 14597

SCNN1A-

+ AGGCACCAGGGAAGGGGCA 19

10749 14598

SCNN1A-

+ CAGGCACCAGGGAAGGGGCA 20

10750 14599

SCNN1A-

+ GCAGGCACCAGGGAAGGGGCA 21

10751 14600

SCNN1A-

+ CGCAGGCACCAGGGAAGGGGCA 22

10752 14601

SCNN1A-

+ GCGCAGGCACCAGGGAAGGGGCA 23

10753 14602

SCNN1A-

+ GGCGCAGGCACCAGGGAAGGGGCA 24

10754 14603

SCNN1A-

+ AGGCGCAGGCACCAGGGA 18

10755 14604

SCNN1A-

+ CAGGCGCAGGCACCAGGGA 19

10756 14605

SCNNlA-6296 + CCAGGCGCAGGCACCAGGGA 20 10145

SCNN1A-

+ UCCAGGCGCAGGCACCAGGGA 21

10757 14606

1504

5535.1 SCNN1A-

+ UUCCAGGCGCAGGCACCAGGGA 22

10758 14607

SCNN1A-

+ CUUCCAGGCGCAGGCACCAGGGA 23

10759 14608

SCNN1A-

+ CCUUCCAGGCGCAGGCACCAGGGA 24

10760 14609

SCNNlA-1452 + CUAACCGACCUGUAGGGA 18 5301

SCNNlA-1453 + ACUAACCGACCUGUAGGGA 19 5302

SCNNlA-1454 + GACUAACCGACCUGUAGGGA 20 5303

SCNNlA-1455 + GGACUAACCGACCUGUAGGGA 21 5304

SCNNlA-1456 + GGGACUAACCGACCUGUAGGGA 22 5305

SCNNlA-1457 + AGGGACUAACCGACCUGUAGGGA 23 5306

SCNNlA-1458 + GAGGGACUAACCGACCUGUAGGGA 24 5307

SCNN1A-

+ AGUGAGCUCUACCUGGGA 18

10761 14610

SCNN1A-

+ CAGUGAGCUCUACCUGGGA 19

10762 14611

SCNN1A-

+ GCAGUGAGCUCUACCUGGGA 20

10763 14612

SCNN1A-

+ AGCAGUGAGCUCUACCUGGGA 21

10764 14613

SCNN1A-

+ CAGCAGUGAGCUCUACCUGGGA 22

10765 14614

SCNN1A-

+ CCAGCAGUGAGCUCUACCUGGGA 23

10766 14615

SCNN1A-

+ GCCAGCAGUGAGCUCUACCUGGGA 24

10767 14616

SCNN1A-

+ CAGCAUUCUAGACCUGGA 18

10768 14617

SCNN1A-

+ GCAGCAUUCUAGACCUGGA 19

10769 14618

SCNN1A-

+ UGCAGCAUUCUAGACCUGGA 20

10770 14619

SCNN1A-

+ CUGCAGCAUUCUAGACCUGGA 21

10771 14620

SCNN1A-

+ GCUGCAGCAUUCUAGACCUGGA 22

10772 14621

SCNN1A-

+ UGCUGCAGCAUUCUAGACCUGGA 23

10773 14622

SCNN1A-

+ GUGCUGCAGCAUUCUAGACCUGGA 24

10774 14623

SCNNlA-1459 + CCCUUCAUGAGCCCUGGA 18 5308

SCNNlA-1460 + CCCCUUCAUGAGCCCUGGA 19 5309

1505

5535.1 SCNNlA-205 + UCCCCUUCAUGAGCCCUGGA 20 833

SCNNlA-1461 + UUCCCCUUCAUGAGCCCUGGA 21 5310

SCNNlA-1462 + GUUCCCCUUCAUGAGCCCUGGA 22 5311

SCNNlA-1463 + UGUUCCCCUUCAUGAGCCCUGGA 23 5312

SCNNlA-1464 + UUGUUCCCCUUCAUGAGCCCUGGA 24 5313

SCNN1A-

+ UAUAGUUCUUUUUUAUGA 18

10775 14624

SCNN1A-

+ AUAUAGUUCUUUUUUAUGA 19

10776 14625

SCNN1A-

+ UAUAUAGUUCUUUUUUAUGA 20

10777 14626

SCNN1A-

+ AUAUAUAGUUCUUUUUUAUGA 21

10778 14627

SCNN1A-

+ AAUAUAUAGUUCUUUUUUAUGA 22

10779 14628

SCNN1A-

+ AAAUAUAUAGUUCUUUUUUAUGA 23

10780 14629

SCNN1A-

+ AAAAUAUAUAGUUCUUUUUUAUGA 24

10781 14630

SCNN1A-

+ UACAAUUUUUCAGCAAUA 18

10782 14631

SCNN1A-

+ GUACAAUUUUUCAGCAAUA 19

10783 14632

SCNN1A-

+ AG UACAAU U U U U CAGCAAU A 20

10784 14633

SCNN1A-

+ CAGUACAAUUUUUCAGCAAUA 21

10785 14634

SCNN1A-

+ ACAGUACAAUUUUUCAGCAAUA 22

10786 14635

SCNN1A-

+ CACAGUACAAUUUUUCAGCAAUA 23

10787 14636

SCNN1A-

+ UCACAGUACAAUUUUUCAGCAAUA 24

10788 14637

SCNN1A-

+ CAGCAAU ACAGAAGUAU A 18

10789 14638

SCNN1A-

+ U CAG CAAUACAGAAG U AU A 19

10790 14639

SCNN1A-

+ UUCAGCAAUACAGAAGUAUA 20

10791 14640

SCNN1A-

+ UUUCAGCAAUACAGAAGUAUA 21

10792 14641

SCNN1A-

+ UUUUCAGCAAUACAGAAGUAUA 22

10793 14642

1506

5535.1 SCNN1A-

+ UUUUUCAGCAAUACAGAAGUAUA 23

10794 14643

SCNN1A-

+ AU U U U U CAGCAAU ACAG AAG U AU A 24

10795 14644

SCNN1A-

+ GCCACGUCCUGCCGGGUA 18

10796 14645

SCNN1A-

+ UGCCACGUCCUGCCGGGUA 19

10797 14646

SCNNlA-6301 + CUGCCACGUCCUGCCGGGUA 20 10150

SCNN1A-

+ CCUGCCACGUCCUGCCGGGUA 21

10798 14647

SCNN1A-

+ CCCUGCCACGUCCUGCCGGGUA 22

10799 14648

SCNN1A-

+ ACCCUGCCACGUCCUGCCGGGUA 23

10800 14649

SCNN1A-

+ GACCCUGCCACGUCCUGCCGGGUA 24

10801 14650

SCNNlA-1478 + GUGUUGUUGCAGAAGAAC 18 5327

SCNNlA-1479 + GGUGUUGUUGCAGAAGAAC 19 5328

SCNNlA-220 + UGGUGUUGUUGCAGAAGAAC 20 843

SCNNlA-1480 + GUGGUGUUGUUGCAGAAGAAC 21 5329

SCNNlA-1481 + GGUGGUGUUGUUGCAGAAGAAC 22 5330

SCNNlA-1482 + UGGUGGUGUUGUUGCAGAAGAAC 23 5331

SCNNlA-1483 + AUGGUGGUGUUGUUGCAGAAGAAC 24

5332

SCNN1A-

+ CCUUCCAGGCGCAGGCAC 18

10802 14651

SCNN1A-

+ CCCUUCCAGGCGCAGGCAC 19

10803 14652

SCNN1A-

+ ACCCUUCCAGGCGCAGGCAC 20

10804 14653

SCNN1A-

+ CACCCUUCCAGGCGCAGGCAC 21

10805 14654

SCNN1A-

+ CCACCCUUCCAGGCGCAGGCAC 22

10806 14655

SCNN1A-

+ ACCACCCUUCCAGGCGCAGGCAC 23

10807 14656

SCNN1A-

+ GACCACCCUUCCAGGCGCAGGCAC 24

10808 14657

SCNN1A-

+ AAAAUAGAAAUCUGAGAC 18

10809 14658

SCNN1A-

+ GAAAAUAGAAAUCUGAGAC 19

10810 14659

1507

5535.1 SCNN1A-

+ GGAAAAUAGAAAUCUGAGAC 20

10811 14660

SCNN1A-

+ AGGAAAAUAGAAAUCUGAGAC 21

10812 14661

SCNN1A-

+ GAGGAAAAUAGAAAUCUGAGAC 22

10813 14662

SCNN1A-

+ UGAGGAAAAUAGAAAUCUGAGAC 23

10814 14663

SCNN1A-

+ GUGAGGAAAAUAGAAAUCUGAGAC 24

10815 14664

SCNN1A-

+ UGCUGCAGCAUUCUAGAC 18

10816 14665

SCNN1A-

+ GUGCUGCAGCAUUCUAGAC 19

10817 14666

SCNN1A-

+ AGUGCUGCAGCAUUCUAGAC 20

10818 14667

SCNN1A-

+ UAGUGCUGCAGCAUUCUAGAC 21

10819 14668

SCNN1A-

+ CUAGUGCUGCAGCAUUCUAGAC 22

10820 14669

SCNN1A-

+ CCUAGUGCUGCAGCAUUCUAGAC 23

10821 14670

SCNN1A-

+ GCCUAGUGCUGCAGCAUUCUAGAC 24

10822 14671

SCNN1A-

+ AGUGAGCACCUCAGCACC 18

10823 14672

SCNN1A-

+ CAGUGAGCACCUCAGCACC 19

10824 14673

SCNN1A-

+ CC AG U G AG CACC U CAG C ACC 20

10825 14674

SCNN1A-

+ CCCAGUGAGCACCUCAGCACC 21

10826 14675

SCNN1A-

+ GCCCAGUGAGCACCUCAGCACC 22

10827 14676

SCNN1A-

+ UGCCCAGUGAGCACCUCAGCACC 23

10828 14677

SCNN1A-

+ CUGCCCAGUGAGCACCUCAGCACC 24

10829 14678

SCNN1A-

+ CUUCCAGGCGCAGGCACC 18

10830 14679

SCNN1A-

+ CCUUCCAGGCGCAGGCACC 19

10831 14680

SCNNlA-6307 + CCCUUCCAGGCGCAGGCACC 20 10156

1508

5535.1 SCNN1A-

+ ACCCUUCCAGGCGCAGGCACC 21

10832 14681

SCNN1A-

+ CACCCUUCCAGGCGCAGGCACC 22

10833 14682

SCNN1A-

+ CCACCCUUCCAGGCGCAGGCACC 23

10834 14683

SCNN1A-

+ ACCACCCUUCCAGGCGCAGGCACC 24

10835 14684

SCNN1A-

+ GCUGCAGCAUUCUAGACC 18

10836 14685

SCNN1A-

+ UGCUGCAGCAUUCUAGACC 19

10837 14686

SCNNlA-6310 + GUGCUGCAGCAUUCUAGACC 20 10159

SCNN1A-

+ AGUGCUGCAGCAUUCUAGACC 21

10838 14687

SCNN1A-

+ UAGUGCUGCAGCAUUCUAGACC 22

10839 14688

SCNN1A-

+ CUAGUGCUGCAGCAUUCUAGACC 23

10840 14689

SCNN1A-

+ CCUAGUGCUGCAGCAUUCUAGACC 24

10841 14690

SCNN1A-

+ CCAGCAGUGAGCUCUACC 18

10842 14691

SCNN1A-

+ GCCAGCAGUGAGCUCUACC 19

10843 14692

SCNNlA-6312 + UGCCAGCAGUGAGCUCUACC 20 10161

SCNNlA-1504 + UGUUCCCCUUCAUGAGCC 18 5353

SCNNlA-1505 + UUGUUCCCCUUCAUGAGCC 19 5354

SCNNlA-207 + CUUGUUCCCCUUCAUGAGCC 20 834

SCNNlA-1506 + GCUUGUUCCCCUUCAUGAGCC 21 5355

SCNNlA-1510 + CGCUUGUUCCCCUUCAUGAGCC 22 5359

SCNNlA-1511 + ACGCUUGUUCCCCUUCAUGAGCC 23 5360

SCNNlA-1512 + CACGCUUGUUCCCCUUCAUGAGCC 24 5361

SCNNlA-1513 + AGGGCCUCCUCCUCCGCC 18 5362

SCNNlA-1514 + CAGGGCCUCCUCCUCCGCC 19 5363

SCNNlA-213 + UCAGGGCCUCCUCCUCCGCC 20 838

SCNNlA-1515 + AUCAGGGCCUCCUCCUCCGCC 21 5364

SCNNlA-1516 + GAUCAGGGCCUCCUCCUCCGCC 22 5365

SCNNlA-1517 + CGAUCAGGGCCUCCUCCUCCGCC 23 5366

SCNNlA-1518 + UCGAUCAGGGCCUCCUCCUCCGCC 24 5367

SCNNlA-1519 + CAGAGCCACAGCACUGCC 18 5368

SCNNlA-1520 + GCAGAGCCACAGCACUGCC 19 5369

SCNNlA-228 + UGCAGAGCCACAGCACUGCC 20 849

1509

5535.1 SCNNlA-1521 + GUGCAGAGCCACAGCACUGCC 21 5370

SCNNlA-1522 + GGUGCAGAGCCACAGCACUGCC 22 5371

SCNNlA-1523 + AGGUGCAGAGCCACAGCACUGCC 23 5372

SCNNlA-1524 + AAGGUGCAGAGCCACAGCACUGCC 24 5373

SCNNlA-1431 + GAGUGGACUGUGGAGGGC 18 5280

SCNNlA-1432 + GGAGUGGACUGUGGAGGGC 19 5281

SCNNlA-201 + UGGAGUGGACUGUGGAGGGC 20 830

SCNNlA-1358 + CUGGAGUGGACUGUGGAGGGC 21 5207

SCNNlA-1359 + CCUGGAGUGGACUGUGGAGGGC 22 5208

SCNNlA-1360 + CCCUGGAGUGGACUGUGGAGGGC 23 5209

SCNNlA-1311 + GCCCUGGAGUGGACUGUGGAGGGC 24 5160

SCNN1A-

+ UCUAGACCUGGAGCGGGC 18

10844 14693

SCNN1A-

+ UUCUAGACCUGGAGCGGGC 19

10845 14694

SCNN1A-

+ AUUCUAGACCUGGAGCGGGC 20

10846 14695

SCNN1A-

+ CAU UCUAGACCUGGAGCGGGC 21

10847 14696

SCNN1A-

+ GCAUUCUAGACCUGGAGCGGGC 22

10848 14697

SCNN1A-

+ AGCAUUCUAGACCUGGAGCGGGC 23

10849 14698

SCNN1A-

+ CAGCAUUCUAGACCUGGAGCGGGC 24

10850 14699

SCNNlA-1531 + GGUGCAGAUGGUCACUGC 18 5380

SCNNlA-1532 + GGGUGCAGAUGGUCACUGC 19 5381

SCNNlA-38 + AGGGUGCAGAUGGUCACUGC 20 575

SCNNlA-1533 + GAGGGUGCAGAUGGUCACUGC 21 5382

SCNNlA-1534 + UGAGGGUGCAGAUGGUCACUGC 22 5383

SCNNlA-1535 + UUGAGGGUGCAGAUGGUCACUGC 23 5384

SCNNlA-1536 + AUUGAGGGUGCAGAUGGUCACUGC 24 5385

SCNNlA-1537 + UCCUCCGCCGUGGGCUGC 18 5386

SCNNlA-1538 + CUCCUCCGCCGUGGGCUGC 19 5387

SCNNlA-65 + CCUCCUCCGCCGUGGGCUGC 20 594

SCNNlA-1539 + UCCUCCUCCGCCGUGGGCUGC 21 5388

SCNNlA-1540 + CUCCUCCUCCGCCGUGGGCUGC 22 5389

SCNNlA-1541 + CCUCCUCCUCCGCCGUGGGCUGC 23 5390

SCNNlA-1542 + GCCUCCUCCUCCGCCGUGGGCUGC 24 5391

SCNNlA-1543 + GUCUUCAUGCGGUUGUGC 18 5392

SCNNlA-1544 + CGUCUUCAUGCGGUUGUGC 19 5393

SCNNlA-49 + CCGUCUUCAUGCGGUUGUGC 20 582

SCNNlA-1545 + GCCGUCUUCAUGCGGUUGUGC 21 5394

1510

5535.1 SCNNlA-1546 + GGCCGUCUUCAUGCGGUUGUGC 22 5395

SCNNlA-1547 + AGGCCGUCUUCAUGCGGUUGUGC 23 5396

SCNNlA-1548 + AAGGCCGUCUUCAUGCGGUUGUGC 24 5397

SCNNlA-1556 + UCACGCUUGUUCCCCUUC 18 5405

SCNNlA-1557 + CUCACGCUUGUUCCCCUUC 19 5406

SCNNlA-208 + CCUCACGCUUGUUCCCCUUC 20 835

SCNNlA-1558 + UCCUCACGCUUGUUCCCCUUC 21 5407

SCNNlA-1559 + CUCCUCACGCUUGUUCCCCUUC 22 5408

SCNNlA-1560 + GCUCCUCACGCUUGUUCCCCUUC 23 5409

SCNNlA-1561 + UGCUCCUCACGCUUGUUCCCCUUC 24 5410

SCNN1A-

+ U CCU U U CCCU CCCCAAAG 18

10851 14700

SCNN1A-

+ UUCCUUUCCCUCCCCAAAG 19

10852 14701

SCNNlA-6330 + CUUCCUUUCCCUCCCCAAAG 20 10179

SCNN1A-

+ CCUUCCUUUCCCUCCCCAAAG 21

10853 14702

SCNN1A-

+ CCCU U CCU U U CCCU CCCCAAAG 22

10854 14703

SCNN1A-

+ CCCCUUCCUUUCCCUCCCCAAAG 23

10855 14704

SCNN1A-

+ UCCCCUUCCUUUCCCUCCCCAAAG 24

10856 14705

SCNNlA-1562 + AUGGUCACUGCGGGGAAG 18 5411

SCNNlA-1563 + GAUGGUCACUGCGGGGAAG 19 5412

SCNNlA-238 + AGAUGGUCACUGCGGGGAAG 20 858

SCNNlA-1564 + CAGAUGGUCACUGCGGGGAAG 21 5413

SCNNlA-1565 + GCAGAUGGUCACUGCGGGGAAG 22 5414

SCNNlA-1566 + UGCAGAUGGUCACUGCGGGGAAG 23 5415

SCNNlA-1567 + GUGCAGAUGGUCACUGCGGGGAAG 24 5416

SCNN1A-

+ GCACCAGGGAAGGGGCAG 18

10857 14706

SCNN1A-

+ GGCACCAGGGAAGGGGCAG 19

10858 14707

SCNNlA-6334 + AGGCACCAGGGAAGGGGCAG 20 10183

SCNN1A-

+ CAGGCACCAGGGAAGGGGCAG 21

10859 14708

SCNN1A-

+ GCAGGCACCAGGGAAGGGGCAG 22

10860 14709

SCNN1A-

+ CGCAGGCACCAGGGAAGGGGCAG 23

10861 14710

SCNN1A-

+ GCGCAGGCACCAGGGAAGGGGCAG 24

10862 14711

1511

5535.1 SCNNlA-1568 + AUGGUGGUGUUGUUGCAG 18 5417

SCNNlA-1569 + GAUGGUGGUGUUGUUGCAG 19 5418

SCNNlA-221 + GGAUGGUGGUGUUGUUGCAG 20 844

SCNNlA-1570 + UGGAUGGUGGUGUUGUUGCAG 21 5419

SCNNlA-1571 + GUGGAUGGUGGUGUUGUUGCAG 22 5420

SCNNlA-1572 + CGUGGAUGGUGGUGUUGUUGCAG 23 5421

SCNNlA-1573 + CCGUGGAUGGUGGUGUUGUUGCAG 24

5422

SCNNlA-1574 + AAGACGAGCUUGUCCGAG 18 5423

SCNNlA-1575 + GAAGACGAGCUUGUCCGAG 19 5424

SCNNlA-236 + GGAAGACGAGCUUGUCCGAG 20 856

SCNNlA-1576 + GGGAAGACGAGCUUGUCCGAG 21 5425

SCNNlA-1577 + GGGGAAGACGAGCUUGUCCGAG 22 5426

SCNNlA-1578 + CGGGGAAGACGAGCUUGUCCGAG 23 5427

SCNNlA-1579 + GCGGGGAAGACGAGCUUGUCCGAG 24 5428

SCNNlA-1580 + UUGAGGCUGACGGGGUAG 18 5429

SCNNlA-1581 + GUUGAGGCUGACGGGGUAG 19 5430

SCNNlA-232 + UGUUGAGGCUGACGGGGUAG 20 853

SCNNlA-1582 + AUGUUGAGGCUGACGGGGUAG 21 5431

SCNNlA-1583 + GAUGUUGAGGCUGACGGGGUAG 22 5432

SCNNlA-1584 + UGAUGUUGAGGCUGACGGGGUAG 23 5433

SCNNlA-1585 + UUGAUGUUGAGGCUGACGGGGUAG 24

5434

SCNNlA-1586 + GAGCUCUCGGUAGGAGCG 18 5435

SCNNlA-1587 + AGAGCUCUCGGUAGGAGCG 19 5436

SCNNlA-216 + AAGAGCUCUCGGUAGGAGCG 20 840

SCNNlA-1588 + GAAGAGCUCUCGGUAGGAGCG 21 5437

SCNNlA-1589 + CGAAGAGCUCUCGGUAGGAGCG 22 5438

SCNNlA-1590 + UCGAAGAGCUCUCGGUAGGAGCG 23 5439

SCNNlA-1591 + CUCGAAGAGCUCUCGGUAGGAGCG 24 5440

SCNNlA-1592 + GUGCAGAUGGUCACUGCG 18 5441

SCNNlA-1593 + GGUGCAGAUGGUCACUGCG 19 5442

SCNNlA-39 + GGGUGCAGAUGGUCACUGCG 20 518

SCNNlA-1594 + AGGGUGCAGAUGGUCACUGCG 21 5443

SCNNlA-1595 + GAGGGUGCAGAUGGUCACUGCG 22 5444

SCNNlA-1596 + UGAGGGUGCAGAUGGUCACUGCG 23 5445

SCNNlA-1597 + UUGAGGGUGCAGAUGGUCACUGCG 24 5446

SCNNlA-1598 + UUGUUGCAGAAGAACUCG 18 5447

SCNNlA-1599 + GUUGUUGCAGAAGAACUCG 19 5448

SCNNlA-219 + UGUUGUUGCAGAAGAACUCG 20 842

SCNNlA-1600 + GUGUUGUUGCAGAAGAACUCG 21 5449

SCNNlA-1601 + GGUGUUGUUGCAGAAGAACUCG 22 5450

1512

5535.1 SCNNlA-1602 + UGGUGUUGUUGCAGAAGAACUCG 23 5451

SCNNlA-1603 + GUGGUGUUGUUGCAGAAGAACUCG 24

5452

SCNN1A-

+ CAUGCACUAUCCUCUAGG 18

10863 14712

SCNN1A-

+ UCAUGCACUAUCCUCUAGG 19

10864 14713

SCNN1A-

+ AUCAUGCACUAUCCUCUAGG 20

10865 14714

SCNN1A-

+ GAUCAUGCACUAUCCUCUAGG 21

10866 14715

SCNN1A-

+ GGAUCAUGCACUAUCCUCUAGG 22

10867 14716

SCNN1A-

+ AGGAUCAUGCACUAUCCUCUAGG 23

10868 14717

SCNN1A-

+ CAGGAUCAUGCACUAUCCUCUAGG 24

10869 14718

SCNNlA-1611 + AGCUCUCGGUAGGAGCGG 18 5460

SCNNlA-1612 + GAGCUCUCGGUAGGAGCGG 19 5461

SCNNlA-60 + AGAGCUCUCGGUAGGAGCGG 20 590

SCNNlA-1613 + AAGAGCUCUCGGUAGGAGCGG 21 5462

SCNNlA-1614 + GAAGAGCUCUCGGUAGGAGCGG 22 5463

SCNNlA-1615 + CGAAGAGCUCUCGGUAGGAGCGG 23 5464

SCNNlA-1616 + UCGAAGAGCUCUCGGUAGGAGCGG 24 5465

SCNNlA-1617 + AACUCGAAGAGCUCUCGG 18 5466

SCNNlA-1618 + GAACUCGAAGAGCUCUCGG 19 5467

SCNNlA-218 + AGAACUCGAAGAGCUCUCGG 20 841

SCNNlA-1619 + AAGAACUCGAAGAGCUCUCGG 21 5468

SCNNlA-1620 + GAAGAACUCGAAGAGCUCUCGG 22 5469

SCNNlA-1621 + AGAAGAACUCGAAGAGCUCUCGG 23 5470

SCNNlA-1622 + CAGAAGAACUCGAAGAGCUCUCGG 24 5471

SCNN1A-

+ CAGGCGCAGGCACCAGGG 18

10870 14719

SCNN1A-

+ CCAGGCGCAGGCACCAGGG 19

10871 14720

SCNN1A-

+ UCCAGGCGCAGGCACCAGGG 20

10872 14721

SCNN1A-

+ UUCCAGGCGCAGGCACCAGGG 21

10873 14722

SCNN1A-

+ CUUCCAGGCGCAGGCACCAGGG 22

10874 14723

SCNN1A-

+ CCUUCCAGGCGCAGGCACCAGGG 23

10875 14724

1513

5535.1 SCNN1A-

+ CCCUUCCAGGCGCAGGCACCAGGG 24

10876 14725

SCNN1A-

+ CAGGCACCAGGGAAGGGG 18

10877 14726

SCNN1A-

+ GCAGGCACCAGGGAAGGGG 19

10878 14727

SCNN1A-

+ CGCAGGCACCAGGGAAGGGG 20

10879 14728

SCNN1A-

+ GCGCAGGCACCAGGGAAGGGG 21

10880 14729

SCNN1A-

+ GGCGCAGGCACCAGGGAAGGGG 22

10881 14730

SCNN1A-

+ AGGCGCAGGCACCAGGGAAGGGG 23

10882 14731

SCNN1A-

+ CAGGCGCAGGCACCAGGGAAGGGG 24

10883 14732

SCNN1A-

+ UGCAAUGCCUGGUCUGGG 18

10884 14733

SCNN1A-

+ UUGCAAUGCCUGGUCUGGG 19

10885 14734

SCNN1A-

+ AUUGCAAUGCCUGGUCUGGG 20

10886 14735

SCNN1A-

+ AAUUGCAAUGCCUGGUCUGGG 21

10887 14736

SCNN1A-

+ GAAUUGCAAUGCCUGGUCUGGG 22

10888 14737

SCNN1A-

+ AGAAUUGCAAUGCCUGGUCUGGG 23

10889 14738

SCNN1A-

+ AAGAAUUGCAAUGCCUGGUCUGGG 24

10890 14739

SCNNlA-1637 + UCCGAGUUGAGGUUGAUG 18 5486

SCNNlA-1638 + GUCCGAGUUGAGGUUGAUG 19 5487

SCNNlA-235 + UGUCCGAGUUGAGGUUGAUG 20 855

SCNNlA-1639 + UUGUCCGAGUUGAGGUUGAUG 21 5488

SCNNlA-1640 + CUUGUCCGAGUUGAGGUUGAUG 22 5489

SCNNlA-1641 + GCUUGUCCGAGUUGAGGUUGAUG 23 5490

SCNNlA-1642 + AGCUUGUCCGAGUUGAGGUUGAUG 24

5491

SCNNlA-1643 + GGGUGCAGAUGGUCACUG 18 5492

SCNNlA-1644 + AGGGUGCAGAUGGUCACUG 19 5493

SCNNlA-37 + GAGGGUGCAGAUGGUCACUG 20 517

SCNNlA-1645 + UGAGGGUGCAGAUGGUCACUG 21 5494

SCNNlA-1646 + UUGAGGGUGCAGAUGGUCACUG 22 5495

1514

5535.1 SCNNlA-1647 + AUUGAGGGUGCAGAUGGUCACUG 23 5496

SCNNlA-1648 + GAUUGAGGGUGCAGAUGGUCACUG 24

5497

SCNNlA-1649 + GAGCCCUGGAGUGGACUG 18 5498

SCNNlA-1650 + UGAGCCCUGGAGUGGACUG 19 5499

SCNNlA-74 + AUGAGCCCUGGAGUGGACUG 20 601

SCNNlA-1651 + CAUGAGCCCUGGAGUGGACUG 21 5500

SCNNlA-1652 + UCAUGAGCCCUGGAGUGGACUG 22 5501

SCNNlA-1653 + UUCAUGAGCCCUGGAGUGGACUG 23 5502

SCNNlA-1654 + CUUCAUGAGCCCUGGAGUGGACUG 24 5503

SCNNlA-1655 + GAGGGACUAACCGACCUG 18 5504

SCNNlA-1656 + AGAGGGACUAACCGACCUG 19 5505

SCNNlA-1657 + CAGAGGGACUAACCGACCUG 20 5506

SCNNlA-1658 + GCAGAGGGACUAACCGACCUG 21 5507

SCNNlA-1659 + GGCAGAGGGACUAACCGACCUG 22 5508

SCNNlA-1660 + GGGCAGAGGGACUAACCGACCUG 23 5509

SCNNlA-1661 + GGGGCAGAGGGACUAACCGACCUG 24 5510

SCNNlA-1662 + AGGUUGAUGUUGAGGCUG 18 5511

SCNNlA-1663 + GAGGUUGAUGUUGAGGCUG 19 5512

SCNNlA-234 + UGAGGUUGAUGUUGAGGCUG 20 854

SCNNlA-1664 + UUGAGGUUGAUGUUGAGGCUG 21 5513

SCNNlA-1665 + GUUGAGGUUGAUGUUGAGGCUG 22 5514

SCNNlA-1666 + AGUUGAGGUUGAUGUUGAGGCUG 23 5515

SCNNlA-1667 + GAGUUGAGGUUGAUGUUGAGGCUG 24

5516

SCNNlA-1675 + CUCCUCCGCCGUGGGCUG 18 5524

SCNNlA-1676 + CCUCCUCCGCCGUGGGCUG 19 5525

SCNNlA-212 + UCCUCCUCCGCCGUGGGCUG 20 837

SCNNlA-1677 + CUCCUCCUCCGCCGUGGGCUG 21 5526

SCNNlA-1678 + CCUCCUCCUCCGCCGUGGGCUG 22 5527

SCNNlA-1679 + GCCUCCUCCUCCGCCGUGGGCUG 23 5528

SCNNlA-1680 + GGCCUCCUCCUCCGCCGUGGGCUG 24 5529

SCNNlA-1681 + UACAUCAUGCCAAAGGUG 18 5530

SCNNlA-1682 + GUACAUCAUGCCAAAGGUG 19 5531

SCNNlA-229 + AGUACAUCAUGCCAAAGGUG 20 850

SCNNlA-1683 + CAGUACAUCAUGCCAAAGGUG 21 5532

SCNNlA-1684 + CCAGUACAUCAUGCCAAAGGUG 22 5533

SCNNlA-1685 + GCCAGUACAUCAUGCCAAAGGUG 23 5534

SCNNlA-1686 + UGCCAGUACAUCAUGCCAAAGGUG 24 5535

SCNNlA-1687 + GCCCUGGAGUGGACUGUG 18 5536

SCNNlA-1688 + AGCCCUGGAGUGGACUGUG 19 5537

SCNNlA-202 + GAGCCCUGGAGUGGACUGUG 20 831

1515

5535.1 SCNNlA-1689 + UGAGCCCUGGAGUGGACUGUG 21 5538

SCNNlA-1690 + AUGAGCCCUGGAGUGGACUGUG 22 5539

SCNNlA-1691 + CAUGAGCCCUGGAGUGGACUGUG 23 5540

SCNNlA-1692 + UCAUGAGCCCUGGAGUGGACUGUG 24 5541

SCNNlA-1693 + CGUCUUCAUGCGGUUGUG 18 5542

SCNNlA-1694 + CCGUCUUCAUGCGGUUGUG 19 5543

SCNNlA-227 + GCCGUCUUCAUGCGGUUGUG 20 848

SCNNlA-1695 + GGCCGUCUUCAUGCGGUUGUG 21 5544

SCNNlA-1696 + AGGCCGUCUUCAUGCGGUUGUG 22 5545

SCNNlA-1697 + AAGGCCGUCUUCAUGCGGUUGUG 23 5546

SCNNlA-1698 + GAAGGCCGUCUUCAUGCGGUUGUG 24 5547

SCNN1A-

+ AACAGGCUUGGUGUUGUG 18

10891 14740

SCNN1A-

+ GAACAGGCUUGGUGUUGUG 19

10892 14741

SCNNlA-6347 + AGAACAGGCUUGGUGUUGUG 20 10196

SCNN1A-

+ UAGAACAGGCUUGGUGUUGUG 21

10893 14742

SCNN1A-

+ CUAGAACAGGCUUGGUGUUGUG 22

10894 14743

SCNN1A-

+ GCUAGAACAGGCUUGGUGUUGUG 23

10895 14744

SCNN1A-

+ GGCUAGAACAGGCUUGGUGUUGUG 24

10896 14745

SCNNlA-1705 + UGGAUGGUGGUGUUGUUG 18 5554

SCNNlA-1706 + GUGGAUGGUGGUGUUGUUG 19 5555

SCNNlA-222 + CGUGGAUGGUGGUGUUGUUG 20 845

SCNNlA-1707 + CCGUGGAUGGUGGUGUUGUUG 21 5556

SCNNlA-1708 + GCCGUGGAUGGUGGUGUUGUUG 22 5557

SCNNlA-1709 + CGCCGUGGAUGGUGGUGUUGUUG 23 5558

SCNNlA-1710 + GCGCCGUGGAUGGUGGUGUUGUUG 24

5559

SCNN1A-

+ UGUGAGGAAAAUAGAAAU 18

10897 14746

SCNN1A-

+ UUGUGAGGAAAAUAGAAAU 19

10898 14747

SCNN1A-

+ GU UGUGAGGAAAAUAGAAAU 20

10899 14748

SCNN1A-

+ UGUUGUGAGGAAAAUAGAAAU 21

10900 14749

SCNN1A-

+ GUGUUGUGAGGAAAAUAGAAAU 22

10901 14750

SCNN1A- + GGUGUUGUGAGGAAAAUAGAAAU 23 14751

1516

5535.1 10902

SCNN1A-

+ UGGUGUUGUGAGGAAAAUAGAAAU 24

10903 14752

SCNN1A-

+ GGGUAUGGGAGUGGCAAU 18

10904 14753

SCNN1A-

+ CGGGUAUGGGAGUGGCAAU 19

10905 14754

SCNN1A-

+ CCGGGUAUGGGAGUGGCAAU 20

10906 14755

SCNN1A-

+ GCCGGGUAUGGGAGUGGCAAU 21

10907 14756

SCNN1A-

+ UGCCGGGUAUGGGAGUGGCAAU 22

10908 14757

SCNN1A-

+ CUGCCGGGUAUGGGAGUGGCAAU 23

10909 14758

SCNN1A-

+ CCUGCCGGGUAUGGGAGUGGCAAU 24

10910 14759

SCNNlA-1711 + GGAGCGGUGGAACUCGAU 18 5560

SCNNlA-1712 + AGGAGCGGUGGAACUCGAU 19 5561

SCNNlA-214 + UAGGAGCGGUGGAACUCGAU 20 839

SCNNlA-1713 + GUAGGAGCGGUGGAACUCGAU 21 5562

SCNNlA-1714 + GGUAGGAGCGGUGGAACUCGAU 22 5563

SCNNlA-1715 + CGGUAGGAGCGGUGGAACUCGAU 23 5564

SCNNlA-1716 + UCGGUAGGAGCGGUGGAACUCGAU 24 5565

SCNNlA-1723 + AGGGUGCAGAUGGUCACU 18 5572

SCNNlA-1724 + GAGGGUGCAGAUGGUCACU 19 5573

SCNNlA-242 + UGAGGGUGCAGAUGGUCACU 20 859

SCNNlA-1725 + UUGAGGGUGCAGAUGGUCACU 21 5574

SCNNlA-1726 + AUUGAGGGUGCAGAUGGUCACU 22 5575

SCNNlA-1727 + GAUUGAGGGUGCAGAUGGUCACU 23 5576

SCNNlA-1728 + GGAUUGAGGGUGCAGAUGGUCACU 24

5577

SCNNlA-1729 + UGAGCCCUGGAGUGGACU 18 5578

SCNNlA-1730 + AUGAGCCCUGGAGUGGACU 19 5579

SCNNlA-204 + CAUGAGCCCUGGAGUGGACU 20 832

SCNNlA-1731 + UCAUGAGCCCUGGAGUGGACU 21 5580

SCNNlA-1732 + UUCAUGAGCCCUGGAGUGGACU 22 5581

SCNNlA-1733 + CUUCAUGAGCCCUGGAGUGGACU 23 5582

SCNNlA-1734 + CCUUCAUGAGCCCUGGAGUGGACU 24 5583

SCNNlA-1748 + UCUUCAUGCGGUUGUGCU 18 5597

SCNNlA-1749 + GUCUUCAUGCGGUUGUGCU 19 5598

SCNNlA-50 + CGUCUUCAUGCGGUUGUGCU 20 583

SCNNlA-1750 + CCGUCUUCAUGCGGUUGUGCU 21 5599

1517

5535.1 SCNNlA-1751 + GCCGUCUUCAUGCGGUUGUGCU 22 5600

SCNNlA-1752 + GGCCGUCUUCAUGCGGUUGUGCU 23 5601

SCNNlA-1753 + AGGCCGUCUUCAUGCGGUUGUGCU 24 5602

SCNN1A-

+ UUAUUUUCUUAUUUAUCU 18

10911 14760

SCNN1A-

+ UUUAUUUUCUUAUUUAUCU 19

10912 14761

SCNN1A-

+ UUUUAUUUUCUUAUUUAUCU 20

10913 14762

SCNN1A-

+ CUUUUAUUUUCUUAUUUAUCU 21

10914 14763

SCNN1A-

+ GCUUUUAUUUUCUUAUUUAUCU 22

10915 14764

SCNN1A-

+ UGCUUUUAUUUUCUUAUUUAUCU 23

10916 14765

SCNN1A-

+ UUGCUUUUAUUUUCUUAUUUAUCU 24

10917 14766

SCNNlA-1754 + GGGUAGCUGAAGUACUCU 18 5603

SCNNlA-1755 + GGGGUAGCUGAAGUACUCU 19 5604

SCNNlA-231 + CGGGGUAGCUGAAGUACUCU 20 852

SCNNlA-1756 + ACGGGGUAGCUGAAGUACUCU 21 5605

SCNNlA-1757 + GACGGGGUAGCUGAAGUACUCU 22 5606

SCNNlA-1758 + UGACGGGGUAGCUGAAGUACUCU 23 5607

SCNNlA-1759 + CUGACGGGGUAGCUGAAGUACUCU 24 5608

SCNNlA-1760 + UGCUGGGGCGCCGCAGGU 18 5609

SCNNlA-1761 + CUGCUGGGGCGCCGCAGGU 19 5610

SCNNlA-210 + GCUGCUGGGGCGCCGCAGGU 20 836

SCNNlA-1762 + GGCUGCUGGGGCGCCGCAGGU 21 5611

SCNNlA-1763 + GGGCUGCUGGGGCGCCGCAGGU 22 5612

SCNNlA-1764 + UGGGCUGCUGGGGCGCCGCAGGU 23 5613

SCNNlA-1765 + GUGGGCUGCUGGGGCGCCGCAGGU 24 5614

SCNN1A-

+ CAGUUCCCACCCUCAGGU 18

10918 14767

SCNN1A-

+ UCAGUUCCCACCCUCAGGU 19

10919 14768

SCNN1A-

+ GUCAGUUCCCACCCUCAGGU 20

10920 14769

SCNN1A-

+ UGUCAGUUCCCACCCUCAGGU 21

10921 14770

SCNN1A-

+ GUGUCAGUUCCCACCCUCAGGU 22

10922 14771

SCNN1A-

+ GGUGUCAGUUCCCACCCUCAGGU 23

10923 14772

1518

5535.1 SCNN1A-

+ GGGUGUCAGUUCCCACCCUCAGGU 24

10924 14773

SCNNlA-1766 + ACUCGAAGAGCUCUCGGU 18 5615

SCNNlA-1767 + AACUCGAAGAGCUCUCGGU 19 5616

SCNNlA-58 + GAACUCGAAGAGCUCUCGGU 20 524

SCNNlA-1768 + AGAACUCGAAGAGCUCUCGGU 21 5617

SCNNlA-1769 + AAGAACUCGAAGAGCUCUCGGU 22 5618

SCNNlA-1770 + GAAGAACUCGAAGAGCUCUCGGU 23 5619

SCNNlA-1771 + AGAAGAACUCGAAGAGCUCUCGGU 24 5620

SCNN1A-

+ UGCCACGUCCUGCCGGGU 18

10925 14774

SCNN1A-

+ CUGCCACGUCCUGCCGGGU 19

10926 14775

SCNN1A-

+ CCUGCCACGUCCUGCCGGGU 20

10927 14776

SCNN1A-

+ CCCUGCCACGUCCUGCCGGGU 21

10928 14777

SCNN1A-

+ ACCCUGCCACGUCCUGCCGGGU 22

10929 14778

SCNN1A-

+ GACCCUGCCACGUCCUGCCGGGU 23

10930 14779

SCNN1A-

+ UGACCCUGCCACGUCCUGCCGGGU 24

10931 14780

SCNN1A-

+ AGAAUUGCAAUGCCUGGU 18

10932 14781

SCNN1A-

+ AAGAAUUGCAAUGCCUGGU 19

10933 14782

SCNN1A-

+ GAAGAAUUGCAAUGCCUGGU 20

10934 14783

SCNN1A-

+ AGAAGAAUUGCAAUGCCUGGU 21

10935 14784

SCNN1A-

+ GAGAAGAAUUGCAAUGCCUGGU 22

10936 14785

SCNN1A-

+ UGAGAAGAAUUGCAAUGCCUGGU 23

10937 14786

SCNN1A-

+ GUGAGAAGAAUUGCAAUGCCUGGU 24

10938 14787

SCNN1A-

+ UGAGACCUGGACUUUGGU 18

10939 14788

SCNN1A-

+ CUGAGACCUGGACUUUGGU 19

10940 14789

SCNN1A-

+ UCUGAGACCUGGACUUUGGU 20

10941 14790

1519

5535.1 SCNN1A-

+ AUCUGAGACCUGGACUUUGGU 21

10942 14791

SCNN1A-

+ AAUCUGAGACCUGGACUUUGGU 22

10943 14792

SCNN1A-

+ AAAUCUGAGACCUGGACUUUGGU 23

10944 14793

SCNN1A-

+ GAAAUCUGAGACCUGGACUUUGGU 24

10945 14794

SCNN1A-

+ GAACAGGCUUGGUGUUGU 18

10946 14795

SCNN1A-

+ AGAACAGGCUUGGUGUUGU 19

10947 14796

SCNN1A-

+ UAGAACAGGCUUGGUGUUGU 20

10948 14797

SCNN1A-

+ CUAGAACAGGCUUGGUGUUGU 21

10949 14798

SCNN1A-

+ GCUAGAACAGGCUUGGUGUUGU 22

10950 14799

SCNN1A-

+ GGCUAGAACAGGCUUGGUGUUGU 23

10951 14800

SCNN1A-

+ GGGCUAGAACAGGCUUGGUGUUGU 24

10952 14801

SCNNlA-1784 + GCUGGGGCGCCGCAGGUU 18 5633

SCNNlA-1785 + UGCUGGGGCGCCGCAGGUU 19 5634

SCNNlA-69 + CUGCUGGGGCGCCGCAGGUU 20 597

SCNNlA-1786 + GCUGCUGGGGCGCCGCAGGUU 21 5635

SCNNlA-1787 + GGCUGCUGGGGCGCCGCAGGUU 22 5636

SCNNlA-1788 + GGGCUGCUGGGGCGCCGCAGGUU 23 5637

SCNNlA-1789 + UGGGCUGCUGGGGCGCCGCAGGUU 24 5638

SCNN1A-

+ UAGAACAGGCUUGGUGUU 18

10953 14802

SCNN1A-

+ CUAGAACAGGCUUGGUGUU 19

10954 14803

SCNN1A-

+ GCUAGAACAGGCUUGGUGUU 20

10955 14804

SCNN1A-

+ GGCUAGAACAGGCUUGGUGUU 21

10956 14805

SCNN1A-

+ GGGCUAGAACAGGCUUGGUGUU 22

10957 14806

SCNN1A-

+ CGGGCUAGAACAGGCUUGGUGUU 23

10958 14807

SCNN1A-

+ GCGGGCUAGAACAGGCUUGGUGUU 24

10959 14808

1520

5535.1 SCNN1A-

- AG A A A A U A A A AG C A A AAA 18

10960 14809

SCNN1A-

- A AG A A A A U A A A AG C A A A A A 19

10961 14810

SCNNlA-6277 - U A AG A A A A U A A A AG C A A A A A 20 10126

SCNN1A-

- A U A AG A A A A U A A A AG C AAA A A 21

10962 14811

SCNN1A-

- A A U A AG A A A A U A A A AG C A A A A A 22

10963 14812

SCNN1A-

- AAA U A AG A A A A U A A A AG C A A A A A 23

10964 14813

SCNN1A-

- UAAAUAAGAAAAUAAAAGCAAAAA 24

10965 14814

SCNN1A-

- A AG A A A A U A A A AG C A A AA 18

10966 14815

SCNN1A-

- U A AG A A A A U A A A AG C A AA A 19

10967 14816

SCNN1A-

- A U A AG A A A A U A A A AG C A A A A 20

10968 14817

SCNN1A-

- A A U A AG A A A A U A A A AG C A A A A 21

10969 14818

SCNN1A-

- A A A U A AG A A A A U A A A AG C A A A A 22

10970 14819

SCNN1A-

- U A A A U A AG A A A A U A A A AG C A A A A 23

10971 14820

SCNN1A-

- AUAAAUAAGAAAAUAAAAGCAAAA 24

10972 14821

SCNN1A-

- AUGGUCUCUGUCAUAAAA 18

10973 14822

SCNN1A-

- CAUGGUCUCUGUCAUAAAA 19

10974 14823

SCNN1A-

- GCAUGGUCUCUGUCAUAAAA 20

10975 14824

SCNN1A-

- AGCAUGGUCUCUGUCAUAAAA 21

10976 14825

SCNN1A-

- UAGCAUGGUCUCUGUCAUAAAA 22

10977 14826

SCNN1A-

- AUAGCAUGGUCUCUGUCAUAAAA 23

10978 14827

SCNN1A-

- UAUAGCAUGGUCUCUGUCAUAAAA 24

10979 14828

SCNN1A-

- UAAAAGAUCAUCUUUAAA 18

10980 14829

1521

5535.1 SCNN1A-

- U U A A A AG A U C A U C U U U AAA 19

10981 14830

SCNN1A-

- UUUAAAAGAUCAUCUUUAAA 20

10982 14831

SCNN1A-

- CUUUAAAAGAUCAUCUUUAAA 21

10983 14832

SCNN1A-

- ACU U U AAAAG AU CAU CU U U AAA 22

10984 14833

SCNN1A-

- CACUUUAAAAGAUCAUCUUUAAA 23

10985 14834

SCNN1A-

- ACACU U U AAAAG AU CAU CU U U AAA 24

10986 14835

SCNN1A-

- UUUGGGGAGGGAAAGGAA 18

10987 14836

SCNN1A-

- CUUUGGGGAGGGAAAGGAA 19

10988 14837

SCNNlA-6283 - CCUUUGGGGAGGGAAAGGAA 20 10132

SCNN1A-

- CCCUUUGGGGAGGGAAAGGAA 21

10989 14838

SCNN1A-

- CCCCUUUGGGGAGGGAAAGGAA 22

10990 14839

SCNN1A-

- UCCCCUUUGGGGAGGGAAAGGAA 23

10991 14840

SCNN1A-

- CUCCCCUUUGGGGAGGGAAAGGAA 24

10992 14841

SCNN1A-

- UCCCCUUUGGGGAGGGAA 18

10993 14842

SCNN1A-

- CUCCCCUUUGGGGAGGGAA 19

10994 14843

SCNNlA-6285 - GCUCCCCUUUGGGGAGGGAA 20 10134

SCNN1A-

- GGCUCCCCUUUGGGGAGGGAA 21

10995 14844

SCNN1A-

- UGGCUCCCCUUUGGGGAGGGAA 22

10996 14845

SCNN1A-

- GUGGCUCCCCUUUGGGGAGGGAA 23

10997 14846

SCNN1A-

- GGUGGCUCCCCUUUGGGGAGGGAA 24

10998 14847

SCNNlA-1796 - CACUCCAGGGCUCAUGAA 18 5645

SCNNlA-1797 - CCACUCCAGGGCUCAUGAA 19 5646

SCNNlA-11 - UCCACUCCAGGGCUCAUGAA 20 560

SCNNlA-1798 - GUCCACUCCAGGGCUCAUGAA 21 5647

SCNNlA-1799 - AGUCCACUCCAGGGCUCAUGAA 22 5648

1522

5535.1 SCNNlA-1800 - CAGUCCACUCCAGGGCUCAUGAA 23 5649

SCNNlA-1801 - ACAGUCCACUCCAGGGCUCAUGAA 24 5650

SCNN1A-

- GGAAAGGAAGGGGACUAA 18

10999 14848

SCNN1A-

- GGGAAAGGAAGGGGACUAA 19

11000 14849

SCNNlA-6288 - AGGGAAAGGAAGGGGACUAA 20 10137

SCNN1A-

- GAGGGAAAGGAAGGGGACUAA 21

11001 14850

SCNN1A-

- GGAGGGAAAGGAAGGGGACUAA 22

11002 14851

SCNN1A-

- GGGAGGGAAAGGAAGGGGACUAA 23

11003 14852

SCNN1A-

- GGGGAGGGAAAGGAAGGGGACUAA 24

11004 14853

SCNN1A-

- AGGGUGCUGAGGUGCUCA 18

11005 14854

SCNN1A-

- CAGGGUGCUGAGGUGCUCA 19

11006 14855

SCNN1A-

- CCAGGGUGCUGAGGUGCUCA 20

11007 14856

SCNN1A-

- UCCAGGGUGCUGAGGUGCUCA 21

11008 14857

SCNN1A-

- GUCCAGGGUGCUGAGGUGCUCA 22

11009 14858

SCNN1A-

- GGUCCAGGGUGCUGAGGUGCUCA 23

11010 14859

SCNN1A-

- UGGUCCAGGGUGCUGAGGUGCUCA 24

11011 14860

SCNN1A-

- CUUUGGGGAGGGAAAGGA 18

11012 14861

SCNN1A-

- CCUUUGGGGAGGGAAAGGA 19

11013 14862

SCNNlA-6295 - CCCUUUGGGGAGGGAAAGGA 20 10144

SCNN1A-

- CCCCUUUGGGGAGGGAAAGGA 21

11014 14863

SCNN1A-

- UCCCCUUUGGGGAGGGAAAGGA 22

11015 14864

SCNN1A-

- CUCCCCUUUGGGGAGGGAAAGGA 23

11016 14865

SCNN1A-

- GCUCCCCUUUGGGGAGGGAAAGGA 24

11017 14866

SCNN1A- - CUCCCCUUUGGGGAGGGA 18 14867

1523

5535.1 11018

SCNN1A-

- GCUCCCCUUUGGGGAGGGA 19

11019 14868

SCNN1A-

- GGCUCCCCUUUGGGGAGGGA 20

11020 14869

SCNN1A-

- UGGCUCCCCUUUGGGGAGGGA 21

11021 14870

SCNN1A-

- GUGGCUCCCCUUUGGGGAGGGA 22

11022 14871

SCNN1A-

- GGUGGCUCCCCUUUGGGGAGGGA 23

11023 14872

SCNN1A-

- UGGUGGCUCCCCUUUGGGGAGGGA 24

11024 14873

SCNN1A-

- GUGGCUCCCCUUUGGGGA 18

11025 14874

SCNN1A-

- GGUGGCUCCCCUUUGGGGA 19

11026 14875

SCNNlA-6297 - UGGUGGCUCCCCUUUGGGGA 20 10146

SCNN1A-

- AUGGUGGCUCCCCUUUGGGGA 21

11027 14876

SCNN1A-

- UAUGGUGGCUCCCCUUUGGGGA 22

11028 14877

SCNN1A-

- UUAUGGUGGCUCCCCUUUGGGGA 23

11029 14878

SCNN1A-

- AUUAUGGUGGCUCCCCUUUGGGGA 24

11030 14879

SCNNlA-1833 - CCACUCCAGGGCUCAUGA 18 5682

SCNNlA-1834 - UCCACUCCAGGGCUCAUGA 19 5683

SCNNlA-10 - GUCCACUCCAGGGCUCAUGA 20 505

SCNNlA-1835 - AGUCCACUCCAGGGCUCAUGA 21 5684

SCNNlA-1836 - CAGUCCACUCCAGGGCUCAUGA 22 5685

SCNNlA-1837 - ACAGUCCACUCCAGGGCUCAUGA 23 5686

SCNNlA-1838 - CACAGUCCACUCCAGGGCUCAUGA 24 5687

SCNN1A-

- GGGAAAGGAAGGGGACUA 18

11031 14880

SCNN1A-

- AGGGAAAGGAAGGGGACUA 19

11032 14881

SCNNlA-6300 - GAGGGAAAGGAAGGGGACUA 20 10149

SCNN1A-

- GGAGGGAAAGGAAGGGGACUA 21

11033 14882

SCNN1A-

- GGGAGGGAAAGGAAGGGGACUA 22

11034 14883

SCNN1A- - GGGGAGGGAAAGGAAGGGGACUA 23 14884

1524

5535.1 11035

SCNN1A-

- UGGGGAGGGAAAGGAAGGGGACUA 24

11036 14885

SCNNlA-1851 - CGAGUUCCACCGCUCCUA 18 5700

SCNNlA-1852 - UCGAGUUCCACCGCUCCUA 19 5701

SCNNlA-190 - AUCGAGUUCCACCGCUCCUA 20 820

SCNNlA-1853 - GAUCGAGUUCCACCGCUCCUA 21 5702

SCNNlA-1854 - UGAUCGAGUUCCACCGCUCCUA 22 5703

SCNNlA-1855 - CUGAUCGAGUUCCACCGCUCCUA 23 5704

SCNNlA-1856 - CCUGAUCGAGUUCCACCGCUCCUA 24 5705

SCNNlA-1857 - CUCAACAUCAACCUCAAC 18 5706

SCNNlA-1858 - CCUCAACAUCAACCUCAAC 19 5707

SCNNlA-198 - GCCUCAACAUCAACCUCAAC 20 827

SCNNlA-1859 - AGCCUCAACAUCAACCUCAAC 21 5708

SCNNlA-1860 - CAG CC U CAAC AU C AACC U C AAC 22 5709

SCNNlA-1861 - UCAGCCUCAACAUCAACCUCAAC 23 5710

SCNNlA-1862 - GUCAGCCUCAACAUCAACCUCAAC 24 5711

SCNN1A-

- GCAGGCAGAGCCUCAGAC 18

11037 14886

SCNN1A-

- GGCAGGCAGAGCCUCAGAC 19

11038 14887

SCNN1A-

- GGGCAGGCAGAGCCUCAGAC 20

11039 14888

SCNN1A-

- UGGGCAGGCAGAGCCUCAGAC 21

11040 14889

SCNN1A-

- CUGGGCAGGCAGAGCCUCAGAC 22

11041 14890

SCNN1A-

- ACUGGGCAGGCAGAGCCUCAGAC 23

11042 14891

SCNN1A-

- CACUGGGCAGGCAGAGCCUCAGAC 24

11043 14892

SCNNlA-1870 - AGUUCCACCGCUCCUACC 18 5719

SCNNlA-1871 - GAGUUCCACCGCUCCUACC 19 5720

SCNNlA-191 - CGAGUUCCACCGCUCCUACC 20 821

SCNNlA-1872 - UCGAGUUCCACCGCUCCUACC 21 5721

SCNNlA-1873 - AUCGAGUUCCACCGCUCCUACC 22 5722

SCNNlA-1874 - GAUCGAGUUCCACCGCUCCUACC 23 5723

SCNNlA-1875 - UGAUCGAGUUCCACCGCUCCUACC 24 5724

SCNN1A-

- UGCUGCUGUACUCCAGCC 18

11044 14893

SCNN1A-

- AUGCUGCUGUACUCCAGCC 19

11045 14894

SCNN1A- - CAUGCUGCUGUACUCCAGCC 20 14895

1525

5535.1 11046

SCNN1A-

- UCAUGCUGCUGUACUCCAGCC 21

11047 14896

SCNN1A-

- AUCAUGCUGCUGUACUCCAGCC 22

11048 14897

SCNN1A-

- GAUCAUGCUGCUGUACUCCAGCC 23

11049 14898

SCNN1A-

- UGAUCAUGCUGCUGUACUCCAGCC 24

11050 14899

SCNN1A-

- UUCCCUGGUGCCUGCGCC 18

11051 14900

SCNN1A-

- CUUCCCUGGUGCCUGCGCC 19

11052 14901

SCNNlA-6315 - CCUUCCCUGGUGCCUGCGCC 20 10164

SCNN1A-

- CCCUUCCCUGGUGCCUGCGCC 21

11053 14902

SCNN1A-

- CCCCUUCCCUGGUGCCUGCGCC 22

11054 14903

SCNN1A-

- GCCCCUUCCCUGGUGCCUGCGCC 23

11055 14904

SCNN1A-

- UGCCCCUUCCCUGGUGCCUGCGCC 24

11056 14905

SCNNlA-1883 - AGGAGCAGGGGCUGGGCC 18 5732

SCNNlA-1884 - GAGGAGCAGGGGCUGGGCC 19 5733

SCNNlA-182 - UGAGGAGCAGGGGCUGGGCC 20 815

SCNNlA-1885 - GUGAGGAGCAGGGGCUGGGCC 21 5734

SCNNlA-1886 - CGUGAGGAGCAGGGGCUGGGCC 22 5735

SCNNlA-1887 - GCGUGAGGAGCAGGGGCUGGGCC 23 5736

SCNNlA-1888 - AGCGUGAGGAGCAGGGGCUGGGCC 24 5737

SCNNlA-1895 - UCAUGAAGGGGAACAAGC 18 5744

SCNNlA-1896 - CUCAUGAAGGGGAACAAGC 19 5745

SCNNlA-176 - GCUCAUGAAGGGGAACAAGC 20 811

SCNNlA-1897 - GGCUCAUGAAGGGGAACAAGC 21 5746

SCNNlA-1898 - GGGCUCAUGAAGGGGAACAAGC 22 5747

SCNNlA-1899 - AGGGCUCAUGAAGGGGAACAAGC 23 5748

SCNNlA-1900 - CAGGGCUCAUGAAGGGGAACAAGC 24 5749

SCNNlA-1916 - GGAACAAGCGUGAGGAGC 18 5765

SCNNlA-1917 - GGGAACAAGCGUGAGGAGC 19 5766

SCNNlA-14 - GGGGAACAAGCGUGAGGAGC 20 506

SCNNlA-1918 - AGGGGAACAAGCGUGAGGAGC 21 5767

SCNNlA-1919 - AAGGGGAACAAGCGUGAGGAGC 22 5768

SCNNlA-1920 - GAAGGGGAACAAGCGUGAGGAGC 23 5769

SCNNlA-1921 - UGAAGGGGAACAAGCGUGAGGAGC 24 5770

1526

5535.1 SCNNlA-1922 - UGCUCCCAGCACAACCGC 18 5771

SCNNlA-1923 - GUGCUCCCAGCACAACCGC 19 5772

SCNNlA-193 - UGUGCUCCCAGCACAACCGC 20 823

SCNNlA-1924 - GUGUGCUCCCAGCACAACCGC 21 5773

SCNNlA-1925 - GGUGUGCUCCCAGCACAACCGC 22 5774

SCNNlA-1926 - UGGUGUGCUCCCAGCACAACCGC 23 5775

SCNNlA-1927 - CUGGUGUGCUCCCAGCACAACCGC 24 5776

SCNN1A-

- CUUCCCUGGUGCCUGCGC 18

11057 14906

SCNN1A-

- CCUUCCCUGGUGCCUGCGC 19

11058 14907

SCNN1A-

- CCCUUCCCUGGUGCCUGCGC 20

11059 14908

SCNN1A-

- CCCCUUCCCUGGUGCCUGCGC 21

11060 14909

SCNN1A-

- GCCCCUUCCCUGGUGCCUGCGC 22

11061 14910

SCNN1A-

- UGCCCCUUCCCUGGUGCCUGCGC 23

11062 14911

SCNN1A-

- CUGCCCCUUCCCUGGUGCCUGCGC 24

11063 14912

SCNNlA-1948 - GCCCUCCACAGUCCACUC 18 5797

SCNNlA-1949 - AGCCCUCCACAGUCCACUC 19 5798

SCNNlA-170 - UAGCCCUCCACAGUCCACUC 20 808

SCNNlA-1954 - CAGUCCACUCCAGGGCUC 18 5803

SCNNlA-1955 - ACAGUCCACUCCAGGGCUC 19 5804

SCNNlA-171 - CACAGUCCACUCCAGGGCUC 20 809

SCNNlA-1956 - CCACAGUCCACUCCAGGGCUC 21 5805

SCNNlA-1957 - UCCACAGUCCACUCCAGGGCUC 22 5806

SCNNlA-1958 - CUCCACAGUCCACUCCAGGGCUC 23 5807

SCNNlA-1959 - CCUCCACAGUCCACUCCAGGGCUC 24 5808

SCNNlA-1995 - ACUCCAGGGCUCAUGAAG 18 5844

SCNNlA-1996 - CACUCCAGGGCUCAUGAAG 19 5845

SCNNlA-12 - CCACUCCAGGGCUCAUGAAG 20 561

SCNNlA-1997 - UCCACUCCAGGGCUCAUGAAG 21 5846

SCNNlA-1998 - GUCCACUCCAGGGCUCAUGAAG 22 5847

SCNNlA-1999 - AGUCCACUCCAGGGCUCAUGAAG 23 5848

SCNNlA-2000 - CAGUCCACUCCAGGGCUCAUGAAG 24 5849

SCNNlA-2017 - GGGAACAAGCGUGAGGAG 18 5866

SCNNlA-2018 - GGGGAACAAGCGUGAGGAG 19 5867

SCNNlA-179 - AGGGGAACAAGCGUGAGGAG 20 813

SCNNlA-2019 - AAGGGGAACAAGCGUGAGGAG 21 5868

SCNNlA-2020 - GAAGGGGAACAAGCGUGAGGAG 22 5869

1527

5535.1 SCNNlA-2021 - UGAAGGGGAACAAGCGUGAGGAG 23 5870

SCNNlA-2022 - AUGAAGGGGAACAAGCGUGAGGAG 24 5871

SCNNlA-2023 - CAGCAGCCCACGGCGGAG 18 5872

SCNNlA-2024 - CCAGCAGCCCACGGCGGAG 19 5873

SCNNlA-187 - CCCAGCAGCCCACGGCGGAG 20 818

SCNNlA-2025 - CCCCAGCAGCCCACGGCGGAG 21 5874

SCNNlA-2026 - GCCCCAGCAGCCCACGGCGGAG 22 5875

SCNNlA-2027 - CGCCCCAGCAGCCCACGGCGGAG 23 5876

SCNNlA-2028 - GCGCCCCAGCAGCCCACGGCGGAG 24 5877

SCNNlA-2035 - GCGCCCCAGCAGCCCACG 18 5884

SCNNlA-2036 - GGCGCCCCAGCAGCCCACG 19 5885

SCNNlA-183 - CGGCGCCCCAGCAGCCCACG 20 816

SCNNlA-2037 - GCGGCGCCCCAGCAGCCCACG 21 5886

SCNNlA-2038 - UGCGGCGCCCCAGCAGCCCACG 22 5887

SCNNlA-2039 - CUGCGGCGCCCCAGCAGCCCACG 23 5888

SCNNlA-2040 - CCUGCGGCGCCCCAGCAGCCCACG 24 5889

SCNNlA-2041 - CCCCAGCAGCCCACGGCG 18 5890

SCNNlA-2042 - GCCCCAGCAGCCCACGGCG 19 5891

SCNNlA-185 - CGCCCCAGCAGCCCACGGCG 20 817

SCNNlA-2043 - GCGCCCCAGCAGCCCACGGCG 21 5892

SCNNlA-2044 - GGCGCCCCAGCAGCCCACGGCG 22 5893

SCNNlA-2045 - CGGCGCCCCAGCAGCCCACGGCG 23 5894

SCNNlA-2046 - GCGGCGCCCCAGCAGCCCACGGCG 24 5895

SCNN1A-

- CCUUUGGGGAGGGAAAGG 18

11064 14913

SCNN1A-

- CCCUUUGGGGAGGGAAAGG 19

11065 14914

SCNN1A-

- CCCCUUUGGGGAGGGAAAGG 20

11066 14915

SCNN1A-

- UCCCCUUUGGGGAGGGAAAGG 21

11067 14916

SCNN1A-

- CUCCCCUUUGGGGAGGGAAAGG 22

11068 14917

SCNN1A-

- GCUCCCCUUUGGGGAGGGAAAGG 23

11069 14918

SCNN1A-

- GGCUCCCCUUUGGGGAGGGAAAGG 24

11070 14919

SCNN1A-

- UGACACCCCUGUCCCAGG 18

11071 14920

SCNN1A-

- CUGACACCCCUGUCCCAGG 19

11072 14921

SCNN1A-

- ACUGACACCCCUGUCCCAGG 20

11073 14922

1528

5535.1 SCNN1A-

- AACUGACACCCCUGUCCCAGG 21

11074 14923

SCNN1A-

- GAACUGACACCCCUGUCCCAGG 22

11075 14924

SCNN1A-

- GGAACUGACACCCCUGUCCCAGG 23

11076 14925

SCNN1A-

- GGGAACUGACACCCCUGUCCCAGG 24

11077 14926

SCNN1A-

- AGGUGCUCACUGGGCAGG 18

11078 14927

SCNN1A-

- GAGGUGCUCACUGGGCAGG 19

11079 14928

SCNN1A-

- UGAGGUGCUCACUGGGCAGG 20

11080 14929

SCNN1A-

- CUGAGGUGCUCACUGGGCAGG 21

11081 14930

SCNN1A-

- GCUGAGGUGCUCACUGGGCAGG 22

11082 14931

SCNN1A-

- UGCUGAGGUGCUCACUGGGCAGG 23

11083 14932

SCNN1A-

- GUGCUGAGGUGCUCACUGGGCAGG 24

11084 14933

SCNNlA-2050 - AGCAGCCCACGGCGGAGG 18 5899

SCNNlA-2051 - CAGCAGCCCACGGCGGAGG 19 5900

SCNNlA-23 - CCAGCAGCCCACGGCGGAGG 20 566

SCNNlA-2052 - CCCAGCAGCCCACGGCGGAGG 21 5901

SCNNlA-2053 - CCCCAGCAGCCCACGGCGGAGG 22 5902

SCNNlA-2054 - GCCCCAGCAGCCCACGGCGGAGG 23 5903

SCNNlA-2055 - CGCCCCAGCAGCCCACGGCGGAGG 24 5904

SCNN1A-

- AGAGCCUCAGACCUGAGG 18

11085 14934

SCNN1A-

- CAGAGCCUCAGACCUGAGG 19

11086 14935

SCNN1A-

- GCAGAGCCUCAGACCUGAGG 20

11087 14936

SCNN1A-

- GGCAGAGCCUCAGACCUGAGG 21

11088 14937

SCNN1A-

- AGGCAGAGCCUCAGACCUGAGG 22

11089 14938

SCNN1A-

- CAGGCAGAGCCUCAGACCUGAGG 23

11090 14939

SCNN1A-

- GCAGGCAGAGCCUCAGACCUGAGG 24

11091 14940

1529

5535.1 SCNNlA-2056 - CGCCCCAGCAGCCCACGG 18 5905

SCNNlA-2057 - GCGCCCCAGCAGCCCACGG 19 5906

SCNNlA-21 - GGCGCCCCAGCAGCCCACGG 20 510

SCNNlA-2058 - CGGCGCCCCAGCAGCCCACGG 21 5907

SCNNlA-2059 - GCGGCGCCCCAGCAGCCCACGG 22 5908

SCNNlA-2060 - UGCGGCGCCCCAGCAGCCCACGG 23 5909

SCNNlA-2061 - CUGCGGCGCCCCAGCAGCCCACGG 24 5910

SCNN1A-

- UGCCACUCCCAUACCCGG 18

11092 14941

SCNN1A-

- UUGCCACUCCCAUACCCGG 19

11093 14942

SCNN1A-

- AUUGCCACUCCCAUACCCGG 20

11094 14943

SCNN1A-

- CAUUGCCACUCCCAUACCCGG 21

11095 14944

SCNN1A-

- GCAUUGCCACUCCCAUACCCGG 22

11096 14945

SCNN1A-

- CGCAUUGCCACUCCCAUACCCGG 23

11097 14946

SCNN1A-

- UCGCAUUGCCACUCCCAUACCCGG 24

11098 14947

SCNNlA-2062 - CCCAGCAGCCCACGGCGG 18 5911

SCNNlA-2063 - CCCCAGCAGCCCACGGCGG 19 5912

SCNNlA-22 - GCCCCAGCAGCCCACGGCGG 20 511

SCNNlA-2064 - CGCCCCAGCAGCCCACGGCGG 21 5913

SCNNlA-2065 - GCGCCCCAGCAGCCCACGGCGG 22 5914

SCNNlA-2066 - GGCGCCCCAGCAGCCCACGGCGG 23 5915

SCNNlA-2067 - CGGCGCCCCAGCAGCCCACGGCGG 24 5916

SCNN1A-

- GAGCCUCAGACCUGAGGG 18

11099 14948

SCNN1A-

- AGAGCCUCAGACCUGAGGG 19

11100 14949

SCNNlA-6341 - CAGAGCCUCAGACCUGAGGG 20 10190

SCNN1A-

- GCAGAGCCUCAGACCUGAGGG 21

11101 14950

SCNN1A-

- GGCAGAGCCUCAGACCUGAGGG 22

11102 14951

SCNN1A-

- AGGCAGAGCCUCAGACCUGAGGG 23

11103 14952

SCNN1A-

- CAGGCAGAGCCUCAGACCUGAGGG 24

11104 14953

SCNNlA-2074 - AAGCGUGAGGAGCAGGGG 18 5923

SCNNlA-2075 - CAAG CG U G AG G AG CAG G GG 19 5924

1530

5535.1 SCNNlA-181 - ACAAGCGUGAGGAGCAGGGG 20 814

SCNNlA-2076 - AACAAGCGUGAGGAGCAGGGG 21 5925

SCNNlA-2077 - GAACAAGCGUGAGGAGCAGGGG 22 5926

SCNNlA-2078 - GGAACAAGCGUGAGGAGCAGGGG 23 5927

SCNNlA-2079 - GGGAACAAGCGUGAGGAGCAGGGG 24 5928

SCNN1A-

- GGUGGCUCCCCUUUGGGG 18

11105 14954

SCNN1A-

- UGGUGGCUCCCCUUUGGGG 19

11106 14955

SCNNlA-6342 - AUGGUGGCUCCCCUUUGGGG 20 10191

SCNN1A-

- UAUGGUGGCUCCCCUUUGGGG 21

11107 14956

SCNN1A-

- UUAUGGUGGCUCCCCUUUGGGG 22

11108 14957

SCNN1A-

- AUUAUGGUGGCUCCCCUUUGGGG 23

11109 14958

SCNN1A-

- AAUUAUGGUGGCUCCCCUUUGGGG 24

11110 14959

SCNN1A-

- UGGUGGCUCCCCUUUGGG 18

11111 14960

SCNN1A-

- AUGGUGGCUCCCCUUUGGG 19

11112 14961

SCNN1A-

- UAUGGUGGCUCCCCUUUGGG 20

11113 14962

SCNN1A-

- UUAUGGUGGCUCCCCUUUGGG 21

11114 14963

SCNN1A-

- AUUAUGGUGGCUCCCCUUUGGG 22

11115 14964

SCNN1A-

- AAUUAUGGUGGCUCCCCUUUGGG 23

11116 14965

SCNN1A-

- AAAUUAUGGUGGCUCCCCUUUGGG 24

11117 14966

SCNNlA-2105 - UCCACUCCAGGGCUCAUG 18 5954

SCNNlA-2106 - GUCCACUCCAGGGCUCAUG 19 5955

SCNNlA-172 - AGUCCACUCCAGGGCUCAUG 20 810

SCNNlA-2107 - CAGUCCACUCCAGGGCUCAUG 21 5956

SCNNlA-2108 - ACAGUCCACUCCAGGGCUCAUG 22 5957

SCNNlA-2109 - CACAGUCCACUCCAGGGCUCAUG 23 5958

SCNNlA-2110 - CCA CAGUCCACUCCAGGGCUCAUG 24 5959

SCNNlA-2137 - UGAAGGGGAACAAGCGUG 18 5986

SCNNlA-2138 - AUGAAGGGGAACAAGCGUG 19 5987

SCNNlA-13 - CA U G AAG GG G AAC AAG CG U G 20 562

SCNNlA-2139 - UCAUGAAGGGGAACAAGCGUG 21 5988

1531

5535.1 SCNNlA-2140 - CUCAUGAAGGGGAACAAGCGUG 22 5989

SCNNlA-2141 - GCUCAUGAAGGGGAACAAGCGUG 23 5990

SCNNlA-2142 - GGCUCAUGAAGGGGAACAAGCGUG 24 5991

SCNN1A-

- GAAGGGUGGUCCAGGGUG 18

11118 14967

SCNN1A-

- GGAAGGGUGGUCCAGGGUG 19

11119 14968

SCNN1A-

- UGGAAGGGUGGUCCAGGGUG 20

11120 14969

SCNN1A-

- CUGGAAGGGUGGUCCAGGGUG 21

11121 14970

SCNN1A-

- CCUGGAAGGGUGGUCCAGGGUG 22

11122 14971

SCNN1A-

- GCCUGGAAGGGUGGUCCAGGGUG 23

11123 14972

SCNN1A-

- CGCCUGGAAGGGUGGUCCAGGGUG 24

11124 14973

SCNN1A-

- CUAUAUACUUCUGUAUUG 18

11125 14974

SCNN1A-

- UCUAUAUACUUCUGUAUUG 19

11126 14975

SCNN1A-

- CUCUAUAUACUUCUGUAUUG 20

11127 14976

SCNN1A-

- GCUCUAUAUACUUCUGUAUUG 21

11128 14977

SCNN1A-

- AGCUCUAUAUACUUCUGUAUUG 22

11129 14978

SCNN1A-

- AAGCUCUAUAUACUUCUGUAUUG 23

11130 14979

SCNN1A-

- GAAGCUCUAUAUACUUCUGUAUUG 24

11131 14980

SCNN1A-

- A AG C A A A A A UGGAAGUUG 18

11132 14981

SCNN1A-

- A A AG C A A A A A UGGAAGUUG 19

11133 14982

SCNN1A-

- A A A AG C A A A A A UGGAAGUUG 20

11134 14983

SCNN1A-

- U A A A AG C A A A A A UGGAAGUUG 21

11135 14984

SCNN1A-

- A U A A A AG C A A A A A UGGAAGUUG 22

11136 14985

SCNN1A-

- A A U A A A AG C A A A A A UGGAAGUUG 23

11137 14986

1532

5535.1 SCNN1A-

- AAAUAAAAGCAAAAAUGGAAGUUG 24

11138 14987

SCNN1A-

- UAUGGUGGCUCCCCUUUG 18

11139 14988

SCNN1A-

- UUAUGGUGGCUCCCCUUUG 19

11140 14989

SCNNlA-6348 - AUUAUGGUGGCUCCCCUUUG 20 10197

SCNN1A-

- AAUUAUGGUGGCUCCCCUUUG 21

11141 14990

SCNN1A-

- AAAUUAUGGUGGCUCCCCUUUG 22

11142 14991

SCNN1A-

- CAAAUUAUGGUGGCUCCCCUUUG 23

11143 14992

SCNN1A-

- ACAAAUUAUGGUGGCUCCCCUUUG 24

11144 14993

SCNN1A-

- CCUGUCUCUAAGAUAAAU 18

11145 14994

SCNN1A-

- UCCUGUCUCUAAGAUAAAU 19

11146 14995

SCNN1A-

- AUCCUGUCUCUAAGAUAAAU 20

11147 14996

SCNN1A-

- GAUCCUGUCUCUAAGAUAAAU 21

11148 14997

SCNN1A-

- UGAUCCUGUCUCUAAGAUAAAU 22

11149 14998

SCNN1A-

- AUGAUCCUGUCUCUAAGAUAAAU 23

11150 14999

SCNN1A-

- CAUGAUCCUGUCUCUAAGAUAAAU 24

11151 15000

SCNN1A-

- AGGGAAAGGAAGGGGACU 18

11152 15001

SCNN1A-

- GAGGGAAAGGAAGGGGACU 19

11153 15002

SCNN1A-

- GGAGGGAAAGGAAGGGGACU 20

11154 15003

SCNN1A-

- GGGAGGGAAAGGAAGGGGACU 21

11155 15004

SCNN1A-

- GGGGAGGGAAAGGAAGGGGACU 22

11156 15005

SCNN1A-

- UGGGGAGGGAAAGGAAGGGGACU 23

11157 15006

SCNN1A-

- UUGGGGAGGGAAAGGAAGGGGACU 24

11158 15007

1533

5535.1 SCNN1A-

- AAUUAUGGUGGCUCCCCU 18

11159 15008

SCNN1A-

- AAAUUAUGGUGGCUCCCCU 19

11160 15009

SCNN1A-

- CAAAUUAUGGUGGCUCCCCU 20

11161 15010

SCNN1A-

- ACAAAUUAUGGUGGCUCCCCU 21

11162 15011

SCNN1A-

- UACAAAUUAUGGUGGCUCCCCU 22

11163 15012

SCNN1A-

- AUACAAAUUAUGGUGGCUCCCCU 23

11164 15013

SCNN1A-

- UAUACAAAUUAUGGUGGCUCCCCU 24

11165 15014

SCNNlA-2170 - AUGAAGGGG A AC A AG CG U 18 6019

SCNNlA-2171 - CAUGAAGGGGAACAAGCGU 19 6020

SCNNlA-177 - UCAUGAAGGGGAACAAGCGU 20 812

SCNNlA-2172 - CUCAUGAAGGGGAACAAGCGU 21 6021

SCNNlA-2173 - GCUCAUGAAGGGGAACAAGCGU 22 6022

SCNNlA-2174 - GGCUCAUGAAGGGGAACAAGCGU 23 6023

SCNNlA-2175 - GGGCUCAUGAAGGGGAACAAGCGU 24 6024

SCNN1A-

- AGCCUCAGACCUGAGGGU 18

11166 15015

SCNN1A-

- GAGCCUCAGACCUGAGGGU 19

11167 15016

SCNNlA-6357 - AGAGCCUCAGACCUGAGGGU 20 10206

SCNN1A-

- CAGAGCCUCAGACCUGAGGGU 21

11168 15017

SCNN1A-

- GCAGAGCCUCAGACCUGAGGGU 22

11169 15018

SCNN1A-

- GGCAGAGCCUCAGACCUGAGGGU 23

11170 15019

SCNN1A-

- AGGCAGAGCCUCAGACCUGAGGGU 24

11171 15020

SCNN1A-

- AUUAUGGUGGCUCCCCUU 18

11172 15021

SCNN1A-

- AAUUAUGGUGGCUCCCCUU 19

11173 15022

SCNNlA-6360 - AAAUUAUGGUGGCUCCCCUU 20 10209

SCNN1A-

- CAAAUUAUGGUGGCUCCCCUU 21

11174 15023

SCNN1A-

- ACAAAUUAUGGUGGCUCCCCUU 22

11175 15024

1534

5535.1 SCNN1A-

- UACAAAUUAUGGUGGCUCCCCUU 23

11176 15025

SCNN1A-

- AUACAAAUUAUGGUGGCUCCCCUU 24

11177 15026

SCNNlA-2183 - CCGCAUGAAGACGGCCUU 18 6032

SCNNlA-2184 - ACCGCAUGAAGACGGCCUU 19 6033

SCNNlA-194 - AACCGCAUGAAGACGGCCUU 20 824

SCNNlA-2185 - CAACCGCAUGAAGACGGCCUU 21 6034

SCNNlA-2186 - ACAACCGCAUGAAGACGGCCUU 22 6035

SCNNlA-2187 - CACAACCGCAUGAAGACGGCCUU 23 6036

SCNNlA-2188 - GCACAACCGCAUGAAGACGGCCUU 24 6037

SCNN1A-

- UUAUGGUGGCUCCCCUUU 18

11178 15027

SCNN1A-

- AUUAUGGUGGCUCCCCUUU 19

11179 15028

SCNNlA-6361 - AAUUAUGGUGGCUCCCCUUU 20 10210

SCNN1A-

- AAAUUAUGGUGGCUCCCCUUU 21

11180 15029

SCNN1A-

- CAAAUUAUGGUGGCUCCCCUUU 22

11181 15030

SCNN1A-

- ACAAAUUAUGGUGGCUCCCCUUU 23

11182 15031

SCNN1A-

- UACAAAUUAUGGUGGCUCCCCUUU 24

11183 15032

SCNNlA-2189 - GGCAAUUCGGCCUGCUUU 18 6038

SCNNlA-2190 - UGGCAAUUCGGCCUGCUUU 19 6039

SCNNlA-195 - CUGGCAAUUCGGCCUGCUUU 20 825

SCNNlA-2191 - ACUGGCAAUUCGGCCUGCUUU 21 6040

SCNNlA-2192 - UACUGGCAAUUCGGCCUGCUUU 22 6041

SCNNlA-2193 - GUACUGGCAAUUCGGCCUGCUUU 23 6042

SCNNlA-2194 - UGUACUGGCAAUUCGGCCUGCUUU 24 6043

SCNNlA-2195 - GCAAUUCGGCCUGCUUUU 18 6044

SCNNlA-2196 - GGCAAUUCGGCCUGCUUUU 19 6045

SCNNlA-34 - UGGCAAUUCGGCCUGCUUUU 20 573

SCNNlA-2197 - CUGGCAAUUCGGCCUGCUUUU 21 6046

SCNNlA-2198 - ACUGGCAAUUCGGCCUGCUUUU 22 6047

SCNNlA-2199 - UACUGGCAAUUCGGCCUGCUUUU 23 6048

SCNNlA-2200 - GUACUGGCAAUUCGGCCUGCUUUU 24 6049

Table 48A provides exemplary targeting domains for knocking down the SCNNIA gene selected according to the first tier parameters. The targeting domains bind within 500 bp (e.g., upstream or downstream) of a transcription start site (TSS), have a high level of orthogonality

1535

5535.1 and start with a 5'G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a N. miningtidis eiCas9 molecule or eiCas9 fusion protein (e.g., an eiCas9 fused to a transcription repressor domain) to alter the SCNNIA gene (e.g., reduce or eliminate SCNNIA gene expression, SCNNIA protein function, or the level of

SCNNIA protein). One or more gRNA may be used to target an eiCas9 to the promoter region of the SCNNIA gene.

Table 48A

Table 48B provides exemplary targeting domains for knocking down the SCNNIA gene selected according to the second tier parameters. The targeting domains bind within 500 bp (e.g. upstream or downstream) of a transcription start site (TSS) and have a high level of

orthogonality. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the

1536

5535.1 table can be used with a N. miningtidis eiCas9 molecule or eiCas9 fusion protein (e.g., an eiCas9 fused to a transcription repressor domain) to alter the SCNNIA gene (e.g., reduce or eliminate SCNNIA gene expression, SCNNIA protein function, or the level of SCNNIA protein). One or more gRNA may be used to target an eiCas9 to the promoter region of the SCNNIA gene.

Table 48B

1537

5535.1 SCNNlA-11227 + UCCUGGUCCCUCCUCUUUCC 20 15076

SCNNlA-11228 + CUGCACGCGGCAGGGAAGGC 20 15077

SCNNlA-11229 + CUUCCCUAGAACGGCCUCUC 20 15078

SCNNlA-11230 + CAGAGUGCAGGAAUGUGGUC 20 15079

SCNNlA-5650 - CAACUCUGUGACCACAGCAG 20 9499

SCNNlA-8013 + UGGGGCCAAAAGUGCCGGAG 20 11862

SCNNlA-5027 + UUCCCCUUCAUGAGCCCCGG 20 8876

SCNNlA-11231 - UCUCCUCCAGCCCUUUUUGG 20 15080

SCNNlA-11232 - CAUGCUGCCUUAAGCUAGUG 20 15081

SCNNlA-11233 - CCUGCUAAACUCCUUGCUUG 20 15082

SCNNlA-11234 + CUUCUAACAAAAGUGCAGAU 20 15083

SCNNlA-11235 - UCUUCUUUGCCUGCUAAACU 20 15084

SCNNlA-11236 + CUCCUCUGGGGCUAUCUACU 20 15085

SCNNlA-11237 - CUCAGGCUGGGCCUUUGUCU 20 15086

SCNNlA-11238 - AUCCUCCCUGCACCUUCAGU 20 15087

Table 48C provides exemplary targeting domains for knocking down the SCNN1A gene selected according to the third tier parameters. The targeting domains bind within 500 bp (e.g., upstream or downstream) of a transcription start site (TSS) and start with a 5'G. It is

contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a N. miningtidis eiCas9 molecule or eiCas9 fusion protein (e.g., an eiCas9 fused to a

transcription repressor domain) to alter the SCNN1A gene (e.g., reduce or eliminate SCNN1A gene expression, SCNN1A protein function, or the level of SCNN1A protein). One or more gRNA may be used to target an eiCas9 to the promoter region of the SCNN1A gene.

Table 48C

Table 48D provides exemplary targeting domains for knocking out the SCNN1A gene selected according to the fourth tier parameters. The targeting domains bind within 500 bp (e.g.,

1538

5535.1 upstream or downstream) of a transcription start site (TSS). It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a N. miningtidis eiCas9 molecule or eiCas9 fusion protein (e.g., an eiCas9 fused to a transcription repressor domain) to alter the SCNNIA gene (e.g., reduce or eliminate SCNNIA gene expression, SCNNIA protein function, or the level of SCNNIA protein). One or more gRNA may be used to target an eiCas9 to the promoter region of the SCNNIA gene.

Table 48D

Table 48E provides exemplary targeting domains for knocking down the SCNNIA gene selected according to the fifth tier parameters. The targeting domains bind within the additional 500 bp (e.g., upstream or downstream) of a transcription start site (TSS), e.g., extending to lkb upstream and downstream of a TSS. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a N. miningtidis eiCas9 molecule or eiCas9 fusion protein (e.g., an eiCas9 fused to a transcription repressor domain) to alter the SCNNIA gene (e.g., reduce or eliminate SCNNIA gene expression, SCNNIA protein function, or the level of SCNNIA protein). One or more gRNA may be used to target an eiCas9 to the promoter region of the SCNNIA gene.

Table 48E

1539

5535.1 SCNN lA-322 + UGGUCACUGCGGGGAAG 17 915

SCN N lA-5023 - GAUGUACUGGCAAUUCG 17 8872

SCN N lA-5025 + AGGGACUAACCGACCUG 17 8874

SCNN lA-11247 + GUUUCUACAACU UCCAU 17 15096

SCNN lA-11248 - CUGACCAAAGUCCAGGU 17 15097

SCNN lA-11249 + UAGACCUGGAGCGGGCUAGA 20 15098

SCNN lA-10791 + UUCAGCAAUACAGAAGUAUA 20 14640

SCN N lA-5031 + CGGGGCCCAGCCCCUGCUCC 20 8880

SCNN lA-238 + AGAUGGUCACUGCGGGGAAG 20 858

SCN N lA-5026 - CAUGAUGUACUGGCAAUUCG 20 8875

SCN N lA-1657 + CAGAGGGACUAACCGACCUG 20 5506

SCNN lA-11250 + UAUGUUUCUACAACUUCCAU 20 15099

SCNN lA-11251 - CUUCUGACCAAAGUCCAGGU 20 15100

III. Cas9 Molecules Cas9 molecules of a variety of species can be used in the methods and compositions described herein. While the S. pyogenes, S. aureus and S. thermophilus Cas9 molecules are the subject of much of the disclosure herein, Cas9 molecules of, derived from, or based on the Cas9 proteins of other species listed herein can be used as well. In other words, while the much of the description herein uses S. pyogenes and S. thermophilus Cas9 molecules, Cas9 molecules from the other species can replace them, e.g., Staphylococcus aureus and Neisseria meningitidis Cas9 molecules. Additional Cas9 species include: Acidovorax avenae, Actinobacillus

pleuropneumoniae, Actinobacillus succinogenes, Actinobacillus suis, Actinomyces sp., cycliphilus denitrificans, Aminomonas paucivorans, Bacillus cereus, Bacillus smithii, Bacillus thuringiensis, Bacteroides sp., Blastopirellula marina, Bradyrhizobium sp., Brevibacillus laterosporus, Campylobacter coli, Campylobacter jejuni, Campylobacter lari, Candidatus Puniceispirillum, Clostridium cellulolyticum, Clostridium perfringens, Corynebacterium accolens, Corynebacterium diphtheria, Corynebacterium matruchotii, Dinoroseobacter shibae, Eubacterium dolichum, gamma proteobacterium, Gluconacetobacter diazotrophicus,

Haemophilus parainfluenzae, Haemophilus sputorum, Helicobacter canadensis, Helicobacter cinaedi, Helicobacter mustelae, Ilyobacter polytropus, Kingella kingae, Lactobacillus crispatus, Listeria ivanovii, Listeria monocytogenes, Listeriaceae bacterium, Methylocystis sp.,

Methylosinus trichosporium, Mobiluncus mulieris, Neisseria bacilliformis, Neisseria cinerea,

1540

5535.1 Neisseria flavescens, Neisseria lactamica, Neisseria meningitidis, Neisseria sp., Neisseria wadsworthii, Nitrosomonas sp., Parvibaculum lavamentivorans, Pasteurella multocida, Phascolarctobacterium succinatutens, Ralstonia syzygii, Rhodopseudomonas palustris,

Rhodovulum sp., Simonsiella muelleri, Sphingomonas sp., Sporolactobacillus vineae,

Staphylococcus lugdunensis, Streptococcus sp., Subdoligranulum sp., Tistrella mobilis,

Treponema sp., or Verminephrobacter eiseniae.

A Cas9 molecule or Cas9 polypeptide, as that term is used herein, refers to a molecule or polypeptide that can interact with a guide RNA (gRNA) molecule and, in concert with the gRNA molecule, home or localizes to a site which comprises a target domain and PAM sequence. Cas9 molecule and Cas9 polypeptide, as those terms are used herein, refer to naturally occurring Cas9 molecules and to engineered, altered, or modified Cas9 molecules or Cas9 polypeptides that differ, e.g., by at least one amino acid residue, from a reference sequence, e.g., the most similar naturally occurring Cas9 molecule or a sequence of Table 50. Cas9 Domains

Crystal structures have been determined for two different naturally occurring bacterial Cas9 molecules (Jinek et al., Science, 343(6176): 1247997, 2014) and for S. pyogenes Cas9 with a guide RNA (e.g., a synthetic fusion of crRNA and tracrRNA) (Nishimasu et al., Cell, 156:935- 949, 2014; and Anders et al., Nature, 2014, doi: 10.1038/naturel3579).

A naturally occurring Cas9 molecule comprises two lobes: a recognition (REC) lobe and a nuclease (NUC) lobe; each of which further comprises domains described herein. Figs. 9A-9B provide a schematic of the organization of important Cas9 domains in the primary structure. The domain nomenclature and the numbering of the amino acid residues encompassed by each domain used throughout this disclosure is as described in Nishimasu et al. The numbering of the amino acid residues is with reference to Cas9 from S. pyogenes.

The REC lobe comprises the arginine-rich bridge helix (BH), the REC1 domain, and the REC2 domain. The REC lobe does not share structural similarity with other known proteins, indicating that it is a Cas9-specific functional domain. The BH domain is a long a helix and arginine rich region and comprises amino acids 60-93 of the sequence of S. pyogenes Cas9. The REC1 domain is important for recognition of the repeat: anti-repeat duplex, e.g., of a gRNA or a tracrRNA, and is therefore critical for Cas9 activity by recognizing the target sequence. The

1541

5535.1 REC1 domain comprises two REC1 motifs at amino acids 94 to 179 and 308 to 717 of the sequence of S. pyogenes Cas9. These two REC1 domains, though separated by the REC2 domain in the linear primary structure, assemble in the tertiary structure to form the REC1 domain. The REC2 domain, or parts thereof, may also play a role in the recognition of the repeat: anti-repeat duplex. The REC2 domain comprises amino acids 180-307 of the sequence of S. pyogenes Cas9.

The NUC lobe comprises the RuvC domain (also referred to herein as RuvC-like domain), the HNH domain (also referred to herein as HNH-like domain), and the PAM- interacting (PI) domain. The RuvC domain shares structural similarity to retroviral integrase superfamily members and cleaves a single strand, e.g., the non-complementary strand of the target nucleic acid molecule. The RuvC domain is assembled from the three split RuvC motifs (RuvC I, RuvCII, and RuvCIII, which are often commonly referred to in the art as RuvCI domain, or N-terminal RuvC domain, RuvCII domain, and RuvCIII domain) at amino acids 1- 59, 718-769, and 909-1098, respectively, of the sequence of S. pyogenes Cas9. Similar to the REC1 domain, the three RuvC motifs are linearly separated by other domains in the primary structure, however in the tertiary structure, the three RuvC motifs assemble and form the RuvC domain. The HNH domain shares structural similarity with HNH endonucleases, and cleaves a single strand, e.g., the complementary strand of the target nucleic acid molecule. The HNH domain lies between the RuvC II-III motifs and comprises amino acids 775-908 of the sequence of S. pyogenes Cas9. The PI domain interacts with the PAM of the target nucleic acid molecule, and comprises amino acids 1099-1368 of the sequence of S. pyogenes Cas9.

A RuvC-like domain and an HNH-like domain

In an embodiment, a Cas9 molecule or Cas9 polypeptide comprises an HNH-like domain and a RuvC-like domain. In an embodiment, cleavage activity is dependent on a RuvC-like domain and an HNH-like domain. A Cas9 molecule or Cas9 polypeptide, e.g., an eaCas9 molecule or eaCas9 polypeptide, can comprise one or more of the following domains: a RuvC- like domain and an HNH-like domain. In an embodiment, a Cas9 molecule or Cas9 polypeptide is an eaCas9 molecule or eaCas9 polypeptide and the eaCas9 molecule or eaCas9 polypeptide comprises a RuvC-like domain, e.g., a RuvC-like domain described below, and/or an HNH-like domain, e.g., an HNH-like domain described below.

1542

5535.1 RuvC-like domains

In an embodiment, a RuvC-like domain cleaves, a single strand, e.g., the non- complementary strand of the target nucleic acid molecule. The Cas9 molecule or Cas9 polypeptide can include more than one RuvC-like domain (e.g., one, two, three or more RuvC- like domains). In an embodiment, a RuvC-like domain is at least 5, 6, 7, 8 amino acids in length but not more than 20, 19, 18, 17, 16 or 15 amino acids in length. In an embodiment, the Cas9 molecule or Cas9 polypeptide comprises an N-terminal RuvC-like domain of about 10 to 20 amino acids, e.g., about 15 amino acids in length.

N-terminal RuvC-like domains

Some naturally occurring Cas9 molecules comprise more than one RuvC-like domain with cleavage being dependent on the N-terminal RuvC-like domain. Accordingly, Cas9 molecules or Cas9 polypeptide can comprise an N-terminal RuvC-like domain. Exemplary N- terminal RuvC-like domains are described below.

In an embodiment, an eaCas9 molecule or eaCas9 polypeptide comprises an N-terminal RuvC-like domain comprising an amino acid sequence of formula I:

D-X1-G-X2-X3-X4-X5-G-X6-X7-X8-X9 (SEQ ID NO: 8),

wherein,

XI is selected from I, V, M, L and T (e.g., selected from I, V, and L);

X2 is selected from T, I, V, S, N, Y, E and L (e.g., selected from T, V, and I);

X3 is selected from N, S, G, A, D, T, R, M and F (e.g., A or N);

X4 is selected from S, Y, N and F (e.g., S);

X5 is selected from V, I, L, C, T and F (e.g., selected from V, I and L);

X6 is selected from W, F, V, Y, S and L (e.g., W);

X7 is selected from A, S, C, V and G (e.g., selected from A and S);

X8 is selected from V, I, L, A, M and H (e.g., selected from V, I, M and L); and

X9 is selected from any amino acid or is absent (e.g., selected from T, V, I, L, Δ, F, S, A, Y, M and R, or, e.g., selected from T, V, I, L and Δ).

In an embodiment, the N-terminal RuvC-like domain differs from a sequence of SEQ ID NO:8, by as many as 1 but no more than 2, 3, 4, or 5 residues.

1543

5535.1 In embodiment, the N-terminal RuvC-like domain is cleavage competent.

In embodiment, the N-terminal RuvC-like domain is cleavage incompetent.

In an embodiment, a eaCas9 molecule or eaCas9 polypeptide comprises an N-terminal RuvC-like domain comprising an amino acid sequence of formula II:

D-X1-G-X2-X3-S-X5-G-X6-X7-X8-X9, (SEQ ID NO: 9),

wherein

XI is selected from I, V, M, L and T (e.g., selected from I, V, and L);

X2 is selected from T, I, V, S, N, Y, E and L (e.g., selected from T, V, and I);

X3 is selected from N, S, G, A, D, T, R, M and F (e.g., A or N);

X5 is selected from V, I, L, C, T and F (e.g., selected from V, I and L);

X6 is selected from W, F, V, Y, S and L (e.g., W);

X7 is selected from A, S, C, V and G (e.g., selected from A and S);

X8 is selected from V, I, L, A, M and H (e.g., selected from V, I, M and L); and

X9 is selected from any amino acid or is absent (e.g., selected from T, V, I, L, Δ, F, S, A, Y, M and R or selected from e.g., T, V, I, L and Δ).

In an embodiment, the N-terminal RuvC-like domain differs from a sequence of SEQ ID NO:9 by as many as 1 but no more than 2, 3, 4, or 5 residues.

In an embodiment, the N-terminal RuvC-like domain comprises an amino acid sequence of formula III:

D-I-G-X2-X3-S-V-G-W-A-X8-X9 (SEQ ID NO: 10),

wherein

X2 is selected from T, I, V, S, N, Y, E and L (e.g., selected from T, V, and I);

X3 is selected from N, S, G, A, D, T, R, M and F (e.g., A or N);

X8 is selected from V, I, L, A, M and H (e.g., selected from V, I, M and L); and

X9 is selected from any amino acid or is absent (e.g., selected from T, V, I, L, Δ, F, S, A,

Y, M and R or selected from e.g., T, V, I, L and Δ).

In an embodiment, the N-terminal RuvC-like domain differs from a sequence of SEQ ID NO: 10 by as many as 1 but no more than, 2, 3, 4, or 5 residues.

In an embodiment, the N-terminal RuvC-like domain comprises an amino acid sequence of formula III:

D-I-G-T-N-S-V-G-W-A-V-X (SEQ ID NO: 11),

1544

5535.1 wherein

X is a non-polar alkyl amino acid or a hydroxyl amino acid, e.g., X is selected from V, I, L and T (e.g., the eaCas9 molecule can comprise an N-terminal RuvC-like domain shown in Figs. 2A-2G (is depicted as Y)).

In an embodiment, the N-terminal RuvC-like domain differs from a sequence of SEQ ID NO: 11 by as many as 1 but no more than, 2, 3, 4, or 5 residues.

In an embodiment, the N-terminal RuvC-like domain differs from a sequence of an N- terminal RuvC like domain disclosed herein, e.g., in Figs. 3A-3B or Figs. 7A-7B, as many as 1 but no more than 2, 3, 4, or 5 residues. In an embodiment, 1, 2, 3 or all of the highly conserved residues identified in Figs. 3A-3B or Figs. 7A-7B are present.

In an embodiment, the N-terminal RuvC-like domain differs from a sequence of an N- terminal RuvC-like domain disclosed herein, e.g., in Figs. 4A-4B or Figs. 7A-7B, as many as 1 but no more than 2, 3, 4, or 5 residues. In an embodiment, 1, 2, or all of the highly conserved residues identified in Figs. 4A-4B or Figs. 7A-7B are present.

Additional RuvC-like domains

In addition to the N-terminal RuvC-like domain, the Cas9 molecule or Cas9 polypeptide, e.g., an eaCas9 molecule or eaCas9 polypeptide, can comprise one or more additional RuvC-like domains. In an embodiment, the Cas9 molecule or Cas9 polypeptide can comprise two additional RuvC-like domains. Preferably, the additional RuvC-like domain is at least 5 amino acids in length and, e.g., less than 15 amino acids in length, e.g., 5 to 10 amino acids in length, e.g., 8 amino acids in length.

An additional RuvC-like domain can comprise an amino acid sequence:

I-X1-X2-E-X3-A-R-E (SEQ ID NO: 12), wherein

XI is V or H,

X2 is I, L or V (e.g., I or V); and

X3 is M or T.

In an embodiment, the additional RuvC-like domain comprises the amino acid sequence: I-V-X2-E-M-A-R-E (SEQ ID NO: 13), wherein

X2 is I, L or V (e.g., I or V) (e.g., the eaCas9 molecule or eaCas9 polypeptide can

1545

5535.1 comprise an additional RuvC-like domain shown in Fig. 2A-2G or Figs. 7A-7B (depicted as B)). An additional RuvC-like domain can comprise an amino acid sequence:

H-H-A-X1-D-A-X2-X3 (SEQ ID NO: 14), wherein

XI is H or L;

X2 is R or V; and

X3 is E or V.

In an embodiment, the additional RuvC-like domain comprises the amino acid sequence: H-H-A-H-D-A-Y-L (SEQ ID NO: 15).

In an embodiment, the additional RuvC-like domain differs from a sequence of SEQ ID NO: 12, 13, 14 or 15 by as many as 1 but no more than 2, 3, 4, or 5 residues.

In some embodiments, the sequence flanking the N-terminal RuvC-like domain is a sequences of formula V:

K-X1'-Y-X2'-X3'-X4'-Z-T-D-X9'-Y, (SEQ ID NO: 16).

wherein

Χ is selected from K and P,

X2' is selected from V, L, I, and F (e.g., V, I and L);

X3' is selected from G, A and S (e.g., G),

X4' is selected from L, I, V and F (e.g., L);

X9' is selected from D, E, N and Q; and

Z is an N-terminal RuvC-like domain, e.g., as described above.

HNH-like domains

In an embodiment, an HNH-like domain cleaves a single stranded complementary domain, e.g., a complementary strand of a double stranded nucleic acid molecule. In an embodiment, an HNH-like domain is at least 15, 20, 25 amino acids in length but not more than 40, 35 or 30 amino acids in length, e.g., 20 to 35 amino acids in length, e.g., 25 to 30 amino acids in length. Exemplary HNH-like domains are described below.

In an embodiment, an eaCas9 molecule or eaCas9 polypeptide comprises an HNH-like domain having an amino acid sequence of formula VI:

XI -X2-X3-H-X4-X5-P-X6-X7-X8-X9-X 10-X 11 -X 12-X 13-X 14-X 15-N-X 16-X 17-X 18-

X19-X20-X21-X22-X23-N (SEQ ID NO: 17), wherein

1546

5535.1 XI is selected from D, E, Q and N (e.g., D and E);

X2 is selected from L, I, R, Q, V, M and K;

X3 is selected from D and E;

X4 is selected from I, V, T, A and L (e.g., A, I and V);

X5 is selected from V, Y, I, L, F and W (e.g., V, I and L);

X6 is selected from Q, H, R, K, Y, I, L, F and W;

X7 is selected from S, A, D, T and K (e.g., S and A);

X8 is selected from F, L, V, K, Y, M, I, R, A, E, D and Q (e.g., F);

X9 is selected from L, R, T, I, V, S, C, Y, K, F and G;

X10 is selected from K, Q, Y, T, F, L, W, M, A, E, G, and S;

XI I is selected from D, S, N, R, L and T (e.g., D);

X12 is selected from D, N and S;

X13 is selected from S, A, T, G and R (e.g., S);

X14 is selected from I, L, F, S, R, Y, Q, W, D, K and H (e.g., I, L and F);

X15 is selected from D, S, I, N, E, A, H, F, L, Q, M, G, Y and V;

X16 is selected from K, L, R, M, T and F (e.g., L, R and K);

X17 is selected from V, L, I, A and T;

X18 is selected from L, I, V and A (e.g., L and I);

X19 is selected from T, V, C, E, S and A (e.g., T and V);

X20 is selected from R, F, T, W, E, L, N, C, K, V, S, Q, I, Y, H and A;

X21 is selected from S, P, R, K, N, A, H, Q, G and L;

X22 is selected from D, G, T, N, S, K, A, I, E, L, Q, R and Y; and

X23 is selected from K, V, A, E, Y, I, C, L, S, T, G, K, M, D and F.

In an embodiment, a HNH-like domain differs from a sequence of SEQ ID NO: 17 by at least one but no more than, 2, 3, 4, or 5 residues.

In an embodiment, the HNH-like domain is cleavage competent.

In an embodiment, the HNH-like domain is cleavage incompetent.

In an embodiment, an eaCas9 molecule or eaCas9 polypeptide comprises an HNH-like domain comprising an amino acid sequence of formula VII:

XI -X2-X3-H-X4-X5-P-X6-S-X8-X9-X 10-D-D-S-X 14-X 15-N-K- V-L-X 19-X20-X21 -

X22-X23-N (SEQ ID NO: 18),

1547

5535.1 wherein

XI is selected from D and E;

X2 is selected from L, I, R, Q, V, M and K;

X3 is selected from D and E;

X4 is selected from I, V, T, A and L (e.g., A, I and V);

X5 is selected from V, Y, I, L, F and W (e.g., V, I and L);

X6 is selected from Q, H, R, K, Y, I, L, F and W;

X8 is selected from F, L, V, K, Y, M, I, R, A, E, D and Q (e.g., F);

X9 is selected from L, R, T, I, V, S, C, Y, K, F and G;

X10 is selected from K, Q, Y, T, F, L, W, M, A, E, G, and S;

X14 is selected from I, L, F, S, R, Y, Q, W, D, K and H (e.g., I, L and F);

X15 is selected from D, S, I, N, E, A, H, F, L, Q, M, G, Y and V;

X19 is selected from T, V, C, E, S and A (e.g., T and V);

X20 is selected from R, F, T, W, E, L, N, C, K, V, S, Q, I, Y, H and A;

X21 is selected from S, P, R, K, N, A, H, Q, G and L;

X22 is selected from D, G, T, N, S, K, A, I, E, L, Q, R and Y; and

X23 is selected from K, V, A, E, Y, I, C, L, S, T, G, K, M, D and F.

In an embodiment, the HNH-like domain differs from a sequence of SEQ ID NO: 18 by 1, 2, 3, 4, or 5 residues.

In an embodiment, an eaCas9 molecule or eaCas9 polypeptide comprises an HNH-like domain comprising an amino acid sequence of formula VII:

X 1 - V-X3-H-I- V-P-X6-S-X8-X9-X 10-D-D-S-X 14-X 15-N-K- V-L-T-X20-X21 -X22-X23- N (SEQ ID NO: 19),

wherein

XI is selected from D and E;

X3 is selected from D and E;

X6 is selected from Q, H, R, K, Y, I, L and W;

X8 is selected from F, L, V, K, Y, M, I, R, A, E, D and Q (e.g., F);

X9 is selected from L, R, T, I, V, S, C, Y, K, F and G;

X10 is selected from K, Q, Y, T, F, L, W, M, A, E, G, and S;

X14 is selected from I, L, F, S, R, Y, Q, W, D, K and H (e.g., I, L and F);

1548

5535.1 X15 is selected from D, S, I, N, E, A, H, F, L, Q, M, G, Y and V;

X20 is selected from R, F, T, W, E, L, N, C, K, V, S, Q, I, Y, H and A;

X21 is selected from S, P, R, K, N, A, H, Q, G and L;

X22 is selected from D, G, T, N, S, K, A, I, E, L, Q, R and Y; and

X23 is selected from K, V, A, E, Y, I, C, L, S, T, G, K, M, D and F.

In an embodiment, the HNH-like domain differs from a sequence of SEQ ID NO: 19 by 1, 2, 3, 4, or 5 residues.

In an embodiment, an eaCas9 molecule or eaCas9 polypeptide comprises an HNH-like domain having an amino acid sequence of formula VIII:

D-X2-D-H-I-X5-P-Q-X7-F-X9-X 10-D-X 12-S-I-D-N-X 16- V-L-X 19-X20-S-X22-X23-N (SEQ ID NO:20),

wherein

X2 is selected from I and V;

X5 is selected from I and V;

X7 is selected from A and S;

X9 is selected from I and L;

X10 is selected from K and T;

X12 is selected from D and N;

X16 is selected from R, K and L; X19 is selected from T and V;

X20 is selected from S and R;

X22 is selected from K, D and A; and

X23 is selected from E, K, G and N (e.g., the eaCas9 molecule or eaCas9 polypeptide can comprise an HNH-like domain as described herein).

In an embodiment, the HNH-like domain differs from a sequence of SEQ ID NO: 20 by as many as 1 but no more than 2, 3, 4, or 5 residues.

In an embodiment, an eaCas9 molecule or eaCas9 polypeptide comprises the amino acid sequence of formula IX:

L- Y- Y-L-Q-N-G-X 1 ' -D-M- Y-X2' -X3 ' -X4' -X5 ' -L-D-I— X6' -X7 ' -L-S-X8 ' - Y-Z-N-R- X9'-K-X10'-D-X11'-V-P (SEQ ID NO: 21),

wherein

Χ is selected from K and R;

1549

5535.1 X2' is selected from V and T;

X3' is selected from G and D;

X4' is selected from E, Q and D;

X5' is selected from E and D;

X6' is selected from D, N and H;

XV is selected from Y, R and N;

X8' is selected from Q, D and N; X9' is selected from G and E;

X10' is selected from S and G;

XI 1 ' is selected from D and N; and

Z is an HNH-like domain, e.g., as described above.

In an embodiment, the eaCas9 molecule or eaCas9 polypeptide comprises an amino acid sequence that differs from a sequence of SEQ ID NO:21 by as many as 1 but no more than 2, 3, 4, or 5 residues.

In an embodiment, the HNH-like domain differs from a sequence of an HNH-like domain disclosed herein, e.g., in Figs. 5A-5C or Figs. 7A-7B, as many as 1 but no more than 2, 3, 4, or 5 residues. In an embodiment, 1 or both of the highly conserved residues identified in Figs. 5A- 5C or Figs. 7A-7B are present.

In an embodiment, the HNH -like domain differs from a sequence of an HNH-like domain disclosed herein, e.g., in Figs. 6A-6B or Figs. 7A-7B, as many as 1 but no more than 2, 3, 4, or 5 residues. In an embodiment, 1, 2, all 3 of the highly conserved residues identified in Figs. 6A-6B or Figs. 7A-7B are present.

Cas9 Activities

Nuclease and Helicase Activities

In an embodiment, the Cas9 molecule or Cas9 polypeptide is capable of cleaving a target nucleic acid molecule. Typically wild type Cas9 molecules cleave both strands of a target nucleic acid molecule. Cas9 molecules and Cas9 polypeptides can be engineered to alter nuclease cleavage (or other properties), e.g., to provide a Cas9 molecule or Cas9 peolypeptide which is a nickase, or which lacks the ability to cleave target nucleic acid. A Cas9 molecule or Cas9 polypeptide that is capable of cleaving a target nucleic acid molecule is referred to herein as an eaCas9 (an enzymatically active Cas9) molecule or eaCas9 polypeptide. In an embodiment, an

1550

5535.1 eaCas9 molecule or eaCas9 polypeptide, comprises one or more of the following activities:

a nickase activity, i.e., the ability to cleave a single strand, e.g., the non-complementary strand or the complementary strand, of a nucleic acid molecule;

a double stranded nuclease activity, i.e., the ability to cleave both strands of a double stranded nucleic acid and create a double stranded break, which in an embodiment is the presence of two nickase activities;

an endonuclease activity;

an exonuclease activity; and

a helicase activity, i.e., the ability to unwind the helical structure of a double stranded nucleic acid.

In an embodiment, an enzymatically active Cas9 or an eaCas9 molecule or an eaCas9 polypeptide cleaves both DNA strands and results in a double stranded break. In an

embodiment, an eaCas9 molecule or eaCas9 polypeptide cleaves only one strand, e.g., the strand to which the gRNA hybridizes to, or the strand complementary to the strand the gRNA hybridizes with. In an embodiment, an eaCas9 molecule or eaCas9 polypeptide comprises cleavage activity associated with an HNH-like domain. In an embodiment, an eaCas9 molecule or eaCas9 polypeptide comprises cleavage activity associated with an N-terminal RuvC-like domain. In an embodiment, an eaCas9 molecule or eaCas9 polypeptide comprises cleavage activity associated with an HNH-like domain and cleavage activity associated with an N-terminal RuvC-like domain. In an embodiment, an eaCas9 molecule or eaCas9 polypeptide comprises an active, or cleavage competent, HNH-like domain and an inactive, or cleavage incompetent, N- terminal RuvC-like domain. In an embodiment, an eaCas9 molecule or eaCas9 polypeptide comprises an inactive, or cleavage incompetent, HNH-like domain and an active, or cleavage competent, N-terminal RuvC-like domain.

Some Cas9 molecules or Cas9 polypeptides have the ability to interact with a gRNA molecule, and in conjunction with the gRNA molecule localize to a core target domain, but are incapable of cleaving the target nucleic acid, or incapable of cleaving at efficient rates. Cas9 molecules having no, or no substantial, cleavage activity are referred to herein as an eiCas9 molecule or eiCas9 polypeptide. For example, an eiCas9 molecule or eiCas9 polypeptide can lack cleavage activity or have substantially less, e.g., less than 20, 10, 5, 1 or 0.1 % of the

1551

5535.1 cleavage activity of a reference Cas9 molecule or eiCas9 polypeptide, as measured by an assay described herein.

Targeting and PAMs

A Cas9 molecule or Cas9 polypeptide, is a polypeptide that can interact with a guide

RNA (gRNA) molecule and, in concert with the gRNA molecule, localizes to a site which comprises a target domain and PAM sequence.

In an embodiment, the ability of an eaCas9 molecule or eaCas9 polypeptide to interact with and cleave a target nucleic acid is PAM sequence dependent. A PAM sequence is a sequence in the target nucleic acid. In an embodiment, cleavage of the target nucleic acid occurs upstream from the PAM sequence. EaCas9 molecules from different bacterial species can recognize different sequence motifs (e.g., PAM sequences). In an embodiment, an eaCas9 molecule of S. pyogenes recognizes the sequence motif NGG and directs cleavage of a target nucleic acid sequence 1 to 10, e.g., 3 to 5, base pairs upstream from that sequence. See, e.g., Mali et al., SCIENCE 2013; 339(6121): 823-826. In an embodiment, an eaCas9 molecule of S. thermophilus recognizes the sequence motif NGGNG and NNAGAAW (W = A or T) and directs cleavage of a core target nucleic acid sequence 1 to 10, e.g., 3 to 5, base pairs upstream from these sequences. See, e.g., Horvath et al., SCIENCE 2010; 327(5962): 167-170, and Deveau et al., J BACTERIOL 2008; 190(4): 1390-1400. In an embodiment, an eaCas9 molecule of S. mutans recognizes the sequence motif NGG and/or NAAR (R = A or G) and directs cleavage of a core target nucleic acid sequence 1 to 10, e.g., 3 to 5 base pairs, upstream from this sequence. See, e.g., Deveau et al., J BACTERIOL 2008; 190(4): 1390-1400. In an embodiment, an eaCas9 molecule of S. aureus recognizes the sequence motif NNGRR (R = A or G) and directs cleavage of a target nucleic acid sequence 1 to 10, e.g., 3 to 5, base pairs upstream from that sequence. In an embodiment, an eaCas9 molecule of S. aureus recognizes the sequence motif NNGRRN (R = A or G) and directs cleavage of a target nucleic acid sequence 1 to 10, e.g., 3 to 5, base pairs upstream from that sequence. In an embodiment, an eaCas9 molecule of S. aureus recognizes the sequence motif NNGRRT (R = A or G) and directs cleavage of a target nucleic acid sequence 1 to 10, e.g., 3 to 5, base pairs upstream from that sequence. In an embodiment, an eaCas9 molecule of S. aureus recognizes the sequence motif NNGRRV (R = A or G, V = A, G or C) and directs cleavage of a target nucleic acid sequence 1 to 10, e.g., 3 to 5, base pairs upstream from

1552

5535.1 that sequence. In an embodiment, an eaCas9 molecule of Neisseria meningitidis recognizes the sequence motif NNNNGATT or NNNGCTT and directs cleavage of a target nucleic acid sequence 1 to 10, e.g., 3 to 5, base pairs upstream from that sequence. See, e.g., Hou et al., PNAS Early Edition 2013, 1-6. The ability of a Cas9 molecule to recognize a PAM sequence can be determined, e.g., using a transformation assay described in Jinek et al., SCIENCE 2012

337:816. In the aforementioned embodiments, N can be any nucleotide residue, e.g., any of A, G, C or T.

As is discussed herein, Cas9 molecules can be engineered to alter the PAM specificity of the Cas9 molecule.

Exemplary naturally occurring Cas9 molecules are described in Chylinski et al., RNA BIOLOGY 2013 10:5, 727-737. Such Cas9 molecules include Cas9 molecules of a cluster 1 bacterial family, cluster 2 bacterial family, cluster 3 bacterial family, cluster 4 bacterial family, cluster 5 bacterial family, cluster 6 bacterial family, a cluster 7 bacterial family, a cluster 8 bacterial family, a cluster 9 bacterial family, a cluster 10 bacterial family, a cluster 11 bacterial family, a cluster 12 bacterial family, a cluster 13 bacterial family, a cluster 14 bacterial family, a cluster 15 bacterial family, a cluster 16 bacterial family, a cluster 17 bacterial family, a cluster 18 bacterial family, a cluster 19 bacterial family, a cluster 20 bacterial family, a cluster 21 bacterial family, a cluster 22 bacterial family, a cluster 23 bacterial family, a cluster 24 bacterial family, a cluster 25 bacterial family, a cluster 26 bacterial family, a cluster 27 bacterial family, a cluster 28 bacterial family, a cluster 29 bacterial family, a cluster 30 bacterial family, a cluster 31 bacterial family, a cluster 32 bacterial family, a cluster 33 bacterial family, a cluster 34 bacterial family, a cluster 35 bacterial family, a cluster 36 bacterial family, a cluster 37 bacterial family, a cluster 38 bacterial family, a cluster 39 bacterial family, a cluster 40 bacterial family, a cluster 41 bacterial family, a cluster 42 bacterial family, a cluster 43 bacterial family, a cluster 44 bacterial family, a cluster 45 bacterial family, a cluster 46 bacterial family, a cluster 47 bacterial family, a cluster 48 bacterial family, a cluster 49 bacterial family, a cluster 50 bacterial family, a cluster 51 bacterial family, a cluster 52 bacterial family, a cluster 53 bacterial family, a cluster 54 bacterial family, a cluster 55 bacterial family, a cluster 56 bacterial family, a cluster 57 bacterial family, a cluster 58 bacterial family, a cluster 59 bacterial family, a cluster 60 bacterial family, a cluster 61 bacterial family, a cluster 62 bacterial family, a cluster 63 bacterial family, a cluster 64 bacterial family, a

1553

5535.1 cluster 65 bacterial family, a cluster 66 bacterial family, a cluster 67 bacterial family, a cluster 68 bacterial family, a cluster 69 bacterial family, a cluster 70 bacterial family, a cluster 71 bacterial family, a cluster 72 bacterial family, a cluster 73 bacterial family, a cluster 74 bacterial family, a cluster 75 bacterial family, a cluster 76 bacterial family, a cluster 77 bacterial family, or a cluster 78 bacterial family.

Exemplary naturally occurring Cas9 molecules include a Cas9 molecule of a cluster 1 bacterial family. Examples include a Cas9 molecule of: S. pyogenes (e.g., strain SF370, MGAS10270, MGAS10750, MGAS2096, MGAS315, MGAS5005, MGAS6180, MGAS9429, NZ131 and SSI-1), S. thermophilus (e.g., strain LMD-9), S. pseudoporcinus (e.g., strain SPIN 20026), S. mutans (e.g., strain UA159, NN2025), S. macacae (e.g., strain NCTC11558), S.

gallolyticus (e.g., strain UCN34, ATCC BAA-2069), S. equines (e.g., strain ATCC 9812, MGCS 124), S. dysdalactiae (e.g., strain GGS 124), S. bovis (e.g., strain ATCC 700338), S. anginosus (e.g., strain F0211), S. agalactiae (e.g., strain NEM316, A909), Listeria monocytogenes (e.g., strain F6854), Listeria innocua (L. innocua, e.g., strain Clipl l262), Enterococcus italicus (e.g., strain DSM 15952), or Enterococcus faecium (e.g., strain 1,231,408). Additional exemplary

Cas9 molecules are a Cas9 molecule of Neisseria meningitides (Hou et ah, PNAS Early Edition 2013, 1-6 and a S. aureus cas9 molecule.

In an embodiment, a Cas9 molecule or Cas9 polypeptide, e.g., an eaCas9 molecule or eaCas9 polypeptide, comprises an amino acid sequence:

having 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% homology with;

differs at no more than, 2, 5, 10, 15, 20, 30, or 40% of the amino acid residues when compared with;

differs by at least 1, 2, 5, 10 or 20 amino acids, but by no more than 100, 80, 70, 60, 50, 40 or 30 amino acids from; or

is identical to any Cas9 molecule sequence described herein, or a naturally occurring Cas9 molecule sequence, e.g., a Cas9 molecule from a species listed herein or described in Chylinski et al, RNA BIOLOGY 2013 10:5, 727-737; Hou et al, PNAS Early Edition 2013, 1-6; SEQ ID NO: 1-4. In an embodiment, the Cas9 molecule or Cas9 polypeptide comprises one or more of the following activities: a nickase activity; a double stranded cleavage activity (e.g., an

1554

5535.1 endonuclease and/or exonuclease activity); a helicase activity; or the ability, together with a gRNA molecule, to localize to a target nucleic acid.

In an embodiment, a Cas9 molecule or Cas9 polypeptide comprises any of the amino acid sequence of the consensus sequence of Figs. 2A-2G, wherein "*" indicates any amino acid found in the corresponding position in the amino acid sequence of a Cas9 molecule or Cas9

polypeptide of S. pyogenes, S. thermophilus, S. mutans and L. innocua, and "-" indicates any amino acid. In an embodiment, a Cas9 molecule differs from the sequence of the consensus sequence of Figs. 2A-2G by at least 1, but no more than 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid residues. In an embodiment, a Cas9 molecule or Cas9 polypeptide comprises the amino acid sequence of SEQ ID NO:7 of Figs. 7A-7B, wherein "*" indicates any amino acid found in the corresponding position in the amino acid sequence of a Cas9 molecule or Cas9 polypeptide of S. pyogenes, or N. meningitides, "-" indicates any amino acid, and "-" indicates any amino acid or absent. In an embodiment, a Cas9 molecule or Cas9 polypeptide differs from the sequence of SEQ ID NO:6 or 7 disclosed in Figs. 7A-7B by at least 1, but no more than 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid residues.

A comparison of the sequence of a number of Cas9 molecules indicate that certain regions are conserved. These are identified below as:

region 1 ( residuesl to 180, or in the case of region l'residues 120 to 180)

region 2 ( residues360 to 480);

region 3 ( residues 660 to 720);

region 4 ( residues 817 to 900); and

region 5 ( residues 900 to 960);

In an embodiment, a Cas9 molecule or Cas9 polypeptide comprises regions 1-5, together with sufficient additional Cas9 molecule sequence to provide a biologically active molecule, e.g., a Cas9 molecule having at least one activity described herein. In an embodiment, each of regions 1-5, independently, have 50%, 60%, 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% homology with the corresponding residues of a Cas9 molecule or Cas9 polypeptide described herein, e.g., a sequence from Figs. 2A-2G or from Figs. 7A-7B.

In an embodiment, a Cas9 molecule or Cas9 polypeptide, e.g., an eaCas9 molecule or eaCas9 polypeptide, comprises an amino acid sequence referred to as region 1:

having 50%, 60%, 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% homology with

1555

5535.1 amino acids 1-180 (the numbering is according to the motif sequence in Figs. 2A-2G; 52% of residues in the four Cas9 sequences in Figs. 2A-2G are conserved) of the amino acid sequence of Cas9 of S. pyogenes;

differs by at least 1, 2, 5, 10 or 20 amino acids but by no more than 90, 80, 70, 60, 50, 40 or 30 amino acids from amino acids 1-180 of the amino acid sequence of Cas9 of S. pyogenes, S. thermophilus, S. mutans or Listeria innocua; or

is identical to 1-180 of the amino acid sequence of Cas9 of S. pyogenes, S. thermophilus, S. mutans or L. innocua.

In an embodiment, a Cas9 molecule or Cas9 polypeptide, e.g., an eaCas9 molecule or eaCas9 polypeptide, comprises an amino acid sequence referred to as region :

having 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% homology with amino acids 120-180 (55% of residues in the four Cas9 sequences in Figs. 2A- 2G are conserved) of the amino acid sequence of Cas9 of S. pyogenes, S. thermophilus, S.

mutans or L. innocua;

differs by at least 1, 2, or 5 amino acids but by no more than 35, 30, 25, 20 or 10 amino acids from amino acids 120-180 of the amino acid sequence of Cas9 of S. pyogenes, S.

thermophilus, S. mutans or L. innocua ; or

is identical to 120-180 of the amino acid sequence of Cas9 of S. pyogenes, S.

thermophilus, S. mutans or L. innocua.

In an embodiment, a Cas9 molecule or Cas9 polypeptide, e.g., an eaCas9 molecule or eaCas9 polypeptide, comprises an amino acid sequence referred to as region 2:

having 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% homology with amino acids 360-480 (52% of residues in the four Cas9 sequences in Figs. 2A- 2G are conserved) of the amino acid sequence of Cas9 of S. pyogenes, S. thermophilus, S.

mutans or L. innocua;

differs by at least 1, 2, or 5 amino acids but by no more than 35, 30, 25, 20 or 10 amino acids from amino acids 360-480 of the amino acid sequence of Cas9 of S. pyogenes, S.

thermophilus, S. mutans or L. innocua; or

is identical to 360-480 of the amino acid sequence of Cas9 of S. pyogenes, S.

thermophilus, S. mutans or L. innocua.

1556

5535.1 In an embodiment, a Cas9 molecule or Cas9 polypeptide, e.g., an eaCas9 molecule or eaCas9 polypeptide, comprises an amino acid sequence referred to as region 3:

having 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% homology with amino acids 660-720 (56% of residues in the four Cas9 sequences in Figs. 2A- 2G are conserved) of the amino acid sequence of Cas9 of S. pyogenes, S. thermophilus, S. mutans or L. innocua;

differs by at least 1, 2, or 5 amino acids but by no more than 35, 30, 25, 20 or 10 amino acids from amino acids 660-720 of the amino acid sequence of Cas9 of S. pyogenes, S.

thermophilus, S. mutans or L. innocua; or

is identical to 660-720 of the amino acid sequence of Cas9 of S. pyogenes, S.

thermophilus, S. mutans or L. innocua.

In an embodiment, a Cas9 molecule, e.g., an eaCas9 molecule, comprises an amino acid sequence referred to as region 4:

having 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% homology with amino acids 817-900 (55% of residues in the four Cas9 sequences in Figs. 2A-2G are conserved) of the amino acid sequence of Cas9 of S. pyogenes, S. thermophilus, S. mutans or L. innocua;

differs by at least 1, 2, or 5 amino acids but by no more than 35, 30, 25, 20 or 10 amino acids from amino acids 817-900 of the amino acid sequence of Cas9 of S. pyogenes, S.

thermophilus, S. mutans or L. innocua; or

is identical to 817-900 of the amino acid sequence of Cas9 of S. pyogenes, S.

thermophilus, S. mutans or L. innocua.

In an embodiment, a Cas9 molecule or Cas9 polypeptide, e.g., an eaCas9 molecule or eaCas9 polypeptide, comprises an amino acid sequence referred to as region 5:

having 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or

99% homology with amino acids 900-960 (60% of residues in the four Cas9 sequences in Figs. 2A-2G are conserved) of the amino acid sequence of Cas9 of S. pyogenes, S. thermophilus, S. mutans or L. innocua;

differs by at least 1, 2, or 5 amino acids but by no more than 35, 30, 25, 20 or 10 amino acids from amino acids 900-960 of the amino acid sequence of Cas9 of S. pyogenes, S.

thermophilus, S. mutans or L. innocua; or

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5535.1 is identical to 900-960 of the amino acid sequence of Cas9 of S. pyogenes, S. thermophilus, S. mutans or L. innocua.

Engineered or Altered Cas9 Molecules and Cas9 Polypeptides

Cas9 molecules and Cas9 polypeptides described herein, e.g., naturally occurring Cas9 molecules can possess any of a number of properties, including: nickase activity, nuclease activity (e.g., endonuclease and/or exonuclease activity); helicase activity; the ability to associate functionally with a gRNA molecule; and the ability to target (or localize to) a site on a nucleic acid (e.g., PAM recognition and specificity). In an embodiment, a Cas9 molecule or Cas9 polypeptide can include all or a subset of these properties. In typical embodiments, a Cas9 molecule or Cas9 polypeptide have the ability to interact with a gRNA molecule and, in concert with the gRNA molecule, localize to a site in a nucleic acid. Other activities, e.g., PAM specificity, cleavage activity, or helicase activity can vary more widely in Cas9 molecules and Cas9 polypeptides.

Cas9 molecules include engineered Cas9 molecules and engineered Cas9 polypeptides

(engineered, as used in this context, means merely that the Cas9 molecule or Cas9 polypeptide differs from a reference sequences, and implies no process or origin limitation). An engineered Cas9 molecule or Cas9 polypeptide can comprise altered enzymatic properties, e.g., altered nuclease activity, (as compared with a naturally occurring or other reference Cas9 molecule) or altered helicase activity. As discussed herein, an engineered Cas9 molecule or Cas9 polypeptide can have nickase activity (as opposed to double strand nuclease activity). In an embodiment an engineered Cas9 molecule or Cas9 polypeptide can have an alteration that alters its size, e.g., a deletion of amino acid sequence that reduces its size, e.g., without significant effect on one or more, or any Cas9 activity. In an embodiment, an engineered Cas9 molecule or Cas9 polypeptide can comprise an alteration that affects PAM recognition. E.g., an engineered Cas9 molecule can be altered to recognize a PAM sequence other than that recognized by the endogenous wild-type PI domain. In an embodiment, a Cas9 molecule or Cas9 polypeptide can differ in sequence from a naturally occurring Cas9 molecule but not have significant alteration in one or more Cas9 activities.

Cas9 molecules or Cas9 polypeptides with desired properties can be made in a number of ways, e.g., by alteration of a parental, e.g., naturally occurring Cas9 molecules or Cas9

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5535.1 polypeptides to provide an altered Cas9 molecule or Cas9 polypeptide having a desired property. For example, one or more mutations or differences relative to a parental Cas9 molecule, e.g., a naturally occurring or engineered Cas9 molecule, can be introduced. Such mutations and differences comprise: substitutions (e.g., conservative substitutions or substitutions of non- essential amino acids); insertions; or deletions. In an embodiment, a Cas9 molecule or Cas9 polypeptide can comprises one or more mutations or differences, e.g., at least 1, 2, 3, 4, 5, 10, 15, 20, 30, 40 or 50 mutations, but less than 200, 100, or 80 mutations relative to a reference, e.g., a parental, Cas9 molecule.

In an embodiment, a mutation or mutations do not have a substantial effect on a Cas9 activity, e.g. a Cas9 activity described herein. In an embodiment, a mutation or mutations have a substantial effect on a Cas9 activity, e.g. a Cas9 activity described herein.

Non-Cleaving and Modified-Cleavage Cas9 Molecules and Cas9 Polypeptides

In an embodiment, a Cas9 molecule or Cas9 polypeptide comprises a cleavage property that differs from naturally occurring Cas9 molecules, e.g., that differs from the naturally occurring Cas9 molecule having the closest homology. For example, a Cas9 molecule or Cas9 polypeptide can differ from naturally occurring Cas9 molecules, e.g., a Cas9 molecule of S. pyogenes, as follows: its ability to modulate, e.g., decreased or increased, cleavage of a double stranded nucleic acid (endonuclease and/or exonuclease activity), e.g., as compared to a naturally occurring Cas9 molecule (e.g., a Cas9 molecule of S. pyogenes); its ability to modulate, e.g., decreased or increased, cleavage of a single strand of a nucleic acid, e.g., a non-complementary strand of a nucleic acid molecule or a complementary strand of a nucleic acid molecule (nickase activity) , e.g., as compared to a naturally occurring Cas9 molecule (e.g., a Cas9 molecule of S. pyogenes); or the ability to cleave a nucleic acid molecule, e.g., a double stranded or single stranded nucleic acid molecule, can be eliminated.

Modified Cleavage eaCas9 Molecules and eaCas9 Polypeptides

In an embodiment, an eaCas9 molecule or eaCas9 polypeptide comprises one or more of the following activities: cleavage activity associated with an N-terminal RuvC-like domain; cleavage activity associated with an HNH-like domain; cleavage activity associated with an HNH-like domain and cleavage activity associated with an N-terminal RuvC-like domain.

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5535.1 In an embodiment, an eaCas9 molecule or eaCas9 polypeptide comprises an active, or cleavage competent, HNH-like domain (e.g., an HNH-like domain described herein, e.g., SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20 or SEQ ID NO: 21) and an inactive, or cleavage incompetent, N-terminal RuvC-like domain. An exemplary inactive, or cleavage incompetent N-terminal RuvC-like domain can have a mutation of an aspartic acid in an N-terminal RuvC-like domain, e.g., an aspartic acid at position 9 of the consensus sequence disclosed in Figs. 2A-2G or an aspartic acid at position 10 of SEQ ID NO: 7, e.g., can be substituted with an alanine. In an embodiment, the eaCas9 molecule or eaCas9 polypeptide differs from wild type in the N-terminal RuvC-like domain and does not cleave the target nucleic acid, or cleaves with significantly less efficiency, e.g., less than 20, 10, 5, 1 or .1 % of the cleavage activity of a reference Cas9 molecule, e.g., as measured by an assay described herein. The reference Cas9 molecule can by a naturally occurring unmodified Cas9 molecule, e.g., a naturally occurring Cas9 molecule such as a Cas9 molecule of S. pyogenes, or S. thermophilus . In an embodiment, the reference Cas9 molecule is the naturally occurring Cas9 molecule having the closest sequence identity or homology.

In an embodiment, an eaCas9 molecule or eaCas9 polypeptide comprises an inactive, or cleavage incompetent, HNH domain and an active, or cleavage competent, N-terminal RuvC-like domain (e.g., a RuvC-like domain described herein, e.g., SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, or SEQ ID NO: 16). Exemplary inactive, or cleavage incompetent HNH-like domains can have a mutation at one or more of: a histidine in an HNH-like domain, e.g., a histidine shown at position 856 of the consensus sequence disclosed in Figs. 2A-2G, e.g., can be substituted with an alanine; and one or more asparagines in an HNH-like domain, e.g., an asparagine shown at position 870 of the consensus sequence disclosed in Figs. 2A-2G and/or at position 879 of the consensus sequence disclosed in Figs. 2A-2G, e.g., can be substituted with an alanine. In an embodiment, the eaCas9 differs from wild type in the HNH-like domain and does not cleave the target nucleic acid, or cleaves with significantly less efficiency, e.g., less than 20, 10, 5, 1 or 0.1% of the cleavage activity of a reference Cas9 molecule, e.g., as measured by an assay described herein. The reference Cas9 molecule can by a naturally occurring unmodified Cas9 molecule, e.g., a naturally occurring Cas9 molecule such as a Cas9 molecule of S. pyogenes, or S. thermophilus.

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5535.1 In an embodiment, the reference Cas9 molecule is the naturally occurring Cas9 molecule having the closest sequence identity or homology.

Alterations in the Ability to Cleave One or Both Strands of a Target Nucleic Acid

In an embodiment, exemplary Cas9 activities comprise one or more of PAM specificity, cleavage activity, and helicase activity. A mutation(s) can be present, e.g., in one or more RuvC- like domain, e.g., an N-terminal RuvC-like domain; an HNH-like domain; a region outside the RuvC-like domains and the HNH-like domain. In some embodiments, a mutation(s) is present in a RuvC-like domain, e.g., an N-terminal RuvC-like domain. In some embodiments, a mutation(s) is present in an HNH-like domain. In some embodiments, mutations are present in both a RuvC-like domain, e.g., an N-terminal RuvC-like domain and an HNH-like domain.

Exemplary mutations that may be made in the RuvC domain or HNH domain with reference to the S. pyogenes sequence include: D10A, E762A, H840A, N854A, N863A and/or D986A.

In an embodiment, a Cas9 molecule or Cas9 polypeptide is an eiCas9 molecule or eiCas9 polypeptide comprising one or more differences in a RuvC domain and/or in an HNH domain as compared to a reference Cas9 molecule, and the eiCas9 molecule or eiCas9 polypeptide does not cleave a nucleic acid, or cleaves with significantly less efficiency than does wildype, e.g., when compared with wild type in a cleavage assay, e.g., as described herein, cuts with less than 50, 25, 10, or 1% of a reference Cas9 molecule, as measured by an assay described herein.

Whether or not a particular sequence, e.g., a substitution, may affect one or more activity, such as targeting activity, cleavage activity, etc., can be evaluated or predicted, e.g., by evaluating whether the mutation is conservative or by the method described in Section IV. In an embodiment, a "non-essential" amino acid residue, as used in the context of a Cas9 molecule, is a residue that can be altered from the wild-type sequence of a Cas9 molecule, e.g., a naturally occurring Cas9 molecule, e.g., an eaCas9 molecule, without abolishing or more preferably, without substantially altering a Cas9 activity (e.g., cleavage activity), whereas changing an "essential" amino acid residue results in a substantial loss of activity (e.g., cleavage activity).

In an embodiment, a Cas9 molecule or Cas9 polypeptide comprises a cleavage property that differs from naturally occurring Cas9 molecules, e.g., that differs from the naturally occurring Cas9 molecule having the closest homology. For example, a Cas9 molecule or Cas9

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5535.1 polypeptide can differ from naturally occurring Cas9 molecules, e.g., a Cas9 molecule of S aureus, S. pyogenes, or C. jejuni as follows: its ability to modulate, e.g., decreased or increased, cleavage of a double stranded break (endonuclease and/or exonuclease activity), e.g., as compared to a naturally occurring Cas9 molecule (e.g., a Cas9 molecule of S aureus, S.

pyogenes, or C. jejuni); its ability to modulate, e.g., decreased or increased, cleavage of a single strand of a nucleic acid, e.g., a non-complimentary strand of a nucleic acid molecule or a complementary strand of a nucleic acid molecule (nickase activity), e.g., as compared to a naturally occurring Cas9 molecule (e.g., a Cas9 molecule of S aureus, S. pyogenes, or C. jejuni); or the ability to cleave a nucleic acid molecule, e.g., a double stranded or single stranded nucleic acid molecule, can be eliminated.

In an embodiment, the altered Cas9 molecule or Cas9 polypeptide is an eaCas9 molecule or eaCas9 polypeptide comprising one or more of the following activities: cleavage activity associated with a RuvC domain; cleavage activity associated with an HNH domain; cleavage activity associated with an HNH domain and cleavage activity associated with a RuvC domain.

In an embodiment, the altered Cas9 molecule or Cas9 polypeptide is an eiCas9 molecule or eiCas9 polypeptide which does not cleave a nucleic acid molecule (either double stranded or single stranded nucleic acid molecules) or cleaves a nucleic acid molecule with significantly less efficiency, e.g., less than 20, 10, 5, 1 or 0.1% of the cleavage activity of a reference Cas9 molecule, e.g., as measured by an assay described herein. The reference Cas9 molecule can be a naturally occurring unmodified Cas9 molecule, e.g., a naturally occurring Cas9 molecule such as a Cas9 molecule of S. pyogenes, S. thermophilus, S. aureus, C. jejuni or N. meningitidis. In an embodiment, the reference Cas9 molecule is the naturally occurring Cas9 molecule having the closest sequence identity or homology. In an embodiment, the eiCas9 molecule or eiCas9 polypeptide lacks substantial cleavage activity associated with a RuvC domain and cleavage activity associated with an HNH domain.

In an embodiment, the altered Cas9 molecule or Cas9 polypeptide is an eaCas9 molecule or eaCas9 polypeptide comprising the fixed amino acid residues of S. pyogenes shown in the consensus sequence disclosed in Figs. 2A-2G, and has one or more amino acids that differ from the amino acid sequence of S. pyogenes (e.g., has a substitution) at one or more residue (e.g., 2, 3, 5, 10, 15, 20, 30, 50, 70, 80, 90, 100, 200 amino acid residues) represented by an "-" in the consensus sequence disclosed in Figs. 2A-2G or SEQ ID NO:7.

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5535.1 In an embodiment, the altered Cas9 molecule or Cas9 polypeptide comprises a sequence in which:

the sequence corresponding to the fixed sequence of the consensus sequence disclosed in Figs. 2A-2G differs at no more than 1, 2, 3, 4, 5, 10, 15, or 20% of the fixed residues in the consensus sequence disclosed in Figs. 2A-2G;

the sequence corresponding to the residues identified by "*" in the consensus sequence disclosed in Figs. 2A-2G differ at no more than 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, or 40% of the "*" residues from the corresponding sequence of naturally occurring Cas9 molecule, e.g., an S. pyogenes Cas9 molecule; and,

the sequence corresponding to the residues identified by "-" in the consensus sequence disclosed in Figs. 2A-2G differ at no more than 5, 10, 15, 20, 25, 30, 35, 40, 45, 55, or 60% of the "-" residues from the corresponding sequence of naturally occurring Cas9 molecule, e.g., an S. pyogenes Cas9 molecule.

In an embodiment, the altered Cas9 molecule or Cas9 polypeptide is an eaCas9 molecule or eaCas9 polypeptide comprising the fixed amino acid residues of S. thermophilus shown in the consensus sequence disclosed in Figs. 2A-2G, and has one or more amino acids that differ from the amino acid sequence of S. thermophilus (e.g., has a substitution) at one or more residue (e.g., 2, 3, 5, 10, 15, 20, 30, 50, 70, 80, 90, 100, 200 amino acid residues) represented by an "-" in the consensus sequence disclosed in Figs. 2A-2G.

In an embodiment, the altered Cas9 molecule or Cas9 polypeptide comprises a sequence in which:

the sequence corresponding to the fixed sequence of the consensus sequence disclosed in Figs. 2A-2G differs at no more than 1, 2, 3, 4, 5, 10, 15, or 20% of the fixed residues in the consensus sequence disclosed in Figs. 2A-2G;

the sequence corresponding to the residues identified by "*" in the consensus sequence disclosed in Figs. 2A-2G differ at no more than 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, or 40% of the "*" residues from the corresponding sequence of naturally occurring Cas9 molecule, e.g., an S. thermophilus Cas9 molecule; and,

the sequence corresponding to the residues identified by "-" in the consensus sequence disclosed in Figs. 2A-2G differ at no more than 5, 10, 15, 20, 25, 30, 35, 40, 45, 55, or 60% of

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5535.1 the "-" residues from the corresponding sequence of naturally occurring Cas9 molecule, e.g., an S. thermophilus Cas9 molecule.

In an embodiment, the altered Cas9 molecule or Cas9 polypeptide is an eaCas9 molecule or eaCas9 polypeptide comprising the fixed amino acid residues of S. mutans shown in the consensus sequence disclosed in Figs. 2A-2G, and has one or more amino acids that differ from the amino acid sequence of S. mutans (e.g., has a substitution) at one or more residue (e.g., 2, 3, 5, 10, 15, 20, 30, 50, 70, 80, 90, 100, 200 amino acid residues) represented by an "-" in the consensus sequence disclosed in Figs. 2A-2G.

In an embodiment, the altered Cas9 molecule or Cas9 polypeptide comprises a sequence in which:

the sequence corresponding to the fixed sequence of the consensus sequence disclosed in Figs. 2A-2G differs at no more than 1, 2, 3, 4, 5, 10, 15, or 20% of the fixed residues in the consensus sequence disclosed in Figs. 2A-2G;

the sequence corresponding to the residues identified by "*" in the consensus sequence disclosed in Figs. 2A-2G differ at no more than 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, or 40% of the "*" residues from the corresponding sequence of naturally occurring Cas9 molecule, e.g., an S. mutans Cas9 molecule; and,

the sequence corresponding to the residues identified by "-" in the consensus sequence disclosed in Figs. 2A-2G differ at no more than 5, 10, 15, 20, 25, 30, 35, 40, 45, 55, or 60% of the "-" residues from the corresponding sequence of naturally occurring Cas9 molecule, e.g., an S. mutans Cas9 molecule.

In an embodiment, the altered Cas9 molecule or Cas9 polypeptide is an eaCas9 molecule or eaCas9 polypeptide comprising the fixed amino acid residues of L. innocula shown in the consensus sequence disclosed in Figs. 2A-2G, and has one or more amino acids that differ from the amino acid sequence of L. innocula (e.g., has a substitution) at one or more residue (e.g., 2, 3, 5, 10, 15, 20, 30, 50, 70, 80, 90, 100, 200 amino acid residues) represented by an "-"in the consensus sequence disclosed in Figs. 2A-2G.

In an embodiment, the altered Cas9 molecule or Cas9 polypeptide comprises a sequence in which:

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5535.1 the sequence corresponding to the fixed sequence of the consensus sequence disclosed in Figs. 2A-2G differs at no more than 1, 2, 3, 4, 5, 10, 15, or 20% of the fixed residues in the consensus sequence disclosed in Figs. 2A-2G;

the sequence corresponding to the residues identified by "*" in the consensus sequence disclosed in Figs. 2A-2G differ at no more than 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, or 40% of the "*" residues from the corresponding sequence of naturally occurring Cas9 molecule, e.g., an L. innocula Cas9 molecule; and,

the sequence corresponding to the residues identified by "-" in the consensus sequence disclosed in Figs. 2A-2G differ at no more than 5, 10, 15, 20, 25, 30, 35, 40, 45, 55, or 60% of the "-" residues from the corresponding sequence of naturally occurring Cas9 molecule, e.g., an L. innocula Cas9 molecule.

In an embodiment, the altered Cas9 molecule or Cas9 polypeptide , e.g., an eaCas9 molecule or eaCas9 polypeptide, can be a fusion, e.g., of two of more different Cas9 molecules, e.g., of two or more naturally occurring Cas9 molecules of different species. For example, a fragment of a naturally occurring Cas9 molecule of one species can be fused to a fragment of a Cas9 molecule of a second species. As an example, a fragment of a Cas9 molecule of S.

pyogenes comprising an N-terminal RuvC-like domain can be fused to a fragment of a Cas9 molecule of a species other than S. pyogenes (e.g., S. thermophilus) comprising an HNH-like domain.

Cas9 Molecules or Cas9 Polypeptides with Altered PAM Recognition or No PAM Recognition

Naturally occurring Cas9 molecules can recognize specific PAM sequences, for example, the PAM recognition sequences described above for S. pyogenes, S. thermophiles, S. mutans, S. aureus and N. meningitidis.

In an embodiment, a Cas9 molecule or Cas9 polypeptide has the same PAM specificities as a naturally occurring Cas9 molecule. In another embodiment, a Cas9 molecule or Cas9 polypeptide has a PAM specificity not associated with a naturally occurring Cas9 molecule, or a PAM specificity not associated with the naturally occurring Cas9 molecule to which it has the closest sequence homology. For example, a naturally occurring Cas9 molecule or Cas9 polypeptide can be altered, e.g., to alter PAM recognition, e.g., to alter the PAM sequence that

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5535.1 the Cas9 molecule recognizes to decrease off target sites and/or improve specificity; or eliminate a PAM recognition requirement. In an embodiment, a Cas9 molecule or Cas9 polypeptide can be altered, e.g., to increase length of PAM recognition sequence and/or improve Cas9 specificity to high level of identity (e.g., 98%, 99% or 100% match between gRNA and a PAM sequence), e.g., to decrease off target sites and increase specificity. In an embodiment, the length of the PAM recognition sequence is at least 4, 5, 6, 7, 8, 9, 10 or 15 amino acids in length. In an embodiment, the Cas9 specificity requires at least 90%, 95%, 96%, 97%, 98%, 99% or more homology between the gRNA and the PAM sequence. Cas9 molecules or Cas9 polypeptides that recognize different PAM sequences and/or have reduced off-target activity can be generated using directed evolution. Exemplary methods and systems that can be used for directed evolution of Cas9 molecules are described, e.g., in Esvelt et al. NATURE 2011, 472(7344): 499- 503. Candidate Cas9 molecules can be evaluated, e.g., by methods described in Section IV.

Alterations of the PI domain, which mediates PAM recognition, are discussed below. Synthetic Cas9 Molecules and Cas9 Polypeptides with Altered PI Domains

Current genome-editing methods are limited in the diversity of target sequences that can be targeted by the PAM sequence that is recognized by the Cas9 molecule utilized. A synthetic Cas9 molecule (or Syn-Cas9 molecule), or synthetic Cas9 polypeptide (or Syn-Cas9

polypeptide), as that term is used herein, refers to a Cas9 molecule or Cas9 polypeptide that comprises a Cas9 core domain from one bacterial species and a functional altered PI domain, i.e., a PI domain other than that naturally associated with the Cas9 core domain, e.g., from a different bacterial species.

In an embodiment, the altered PI domain recognizes a PAM sequence that is different from the PAM sequence recognized by the naturally- occurring Cas9 from which the Cas9 core domain is derived. In an embodiment, the altered PI domain recognizes the same PAM sequence recognized by the naturally- occurring Cas9 from which the Cas9 core domain is derived, but with different affinity or specificity. A Syn-Cas9 molecule or Syn-Cas9 polypetide can be, respectively, a Syn-eaCas9 molecule or Syn-eaCas9 polypeptide or a Syn-eiCas9 molecule Syn- eiCas9 polypeptide.

An exemplary Syn-Cas9 molecule or Syn-Cas9 polypetide comprises:

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5535.1 a) a Cas9 core domain, e.g., a Cas9 core domain from Table 50 or 51, e.g., a S. aureus, S. pyogenes, or C. jejuni Cas9 core domain; and

b) an altered PI domain from a species X Cas9 sequence selected from Tables 53 and 54. In an embodiment, the RKR motif (the PAM binding motif) of said altered PI domain comprises: differences at 1, 2, or 3 amino acid residues; a difference in amino acid sequence at the first, second, or third position; differences in amino acid sequence at the first and second positions, the first and third positions, or the second and third positions; as compared with the sequence of the RKR motif of the native or endogenous PI domain associated with the Cas9 core domain.

In an embodiment, the Cas9 core domain comprises the Cas9 core domain from a species

X Cas9 from Table 50 and said altered PI domain comprises a PI domain from a species Y Cas9 from Table 50.

In an embodiment, the RKR motif of the species X Cas9 is other than the RKR motif of the species Y Cas9.

In an embodiment, the RKR motif of the altered PI domain is selected from XXY, XNG, and XNQ.

In an embodiment, the altered PI domain has at least 60, 70, 80, 90, 95, or 100% homology with the amino acid sequence of a naturally occurring PI domain of said species Y from Table 50.

In an embodiment, the altered PI domain differs by no more than 50, 40, 30, 25, 20, 15,

10, 5, 4, 3, 2, or 1 amino acid residue from the amino acid sequence of a naturally occurring PI domain of said second species from Table 50.

In an embodiment, the Cas9 core domain comprises a S. aureus core domain and altered

PI domain comprises: an A. denitrificans PI domain; a C. jejuni PI domain; a H. mustelae PI domain; or an altered PI domain of species X PI domain, wherein species X is selected from

Table 54.

In an embodiment, the Cas9 core domain comprises a S. pyogenes core domain and the altered PI domain comprises: an A. denitrificans PI domain; a C. jejuni PI domain; a H. mustelae PI domain; or an altered PI domain of species X PI domain, wherein species X is selected from Table 54.

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5535.1 In an embodiment, the Cas9 core domain comprises a C. jejuni core domain and the altered PI domain comprises: an A. denitrificans PI domain; a H. mustelae PI domain; or an altered PI domain of species X PI domain, wherein species X is selected from Table 54.

In an embodiment, the Cas9 molecule or Cas9 polypeptide further comprises a linker disposed between said Cas9 core domain and said altered PI domain.

In an embodiment, the linker comprises: a linker described elsewhere herein disposed between the Cas9 core domain and the heterologous PI domain. Suitable linkers are further described in Section V.

Exemplary altered PI domains for use in Syn-Cas9 molecules are described in Tables 53 and 54. The sequences for the 83 Cas9 orthologs referenced in Tables 53 and 54 are provided in Table 50. Table 52 provides the Cas9 orthologs with known PAM sequences and the corresponding RKR motif.

In an embodiment, a Syn-Cas9 molecule or Syn-Cas9 polypeptide may also be size- optimized, e.g., the Syn-Cas9 molecule or Syn-Cas9 polypeptide comprises one or more deletions, and optionally one or more linkers disposed between the amino acid residues flanking the deletions. In an embodiment, a Syn-Cas9 molecule or Syn-Cas9 polypeptide comprises a REC deletion.

Size-Optimized Cas9 Molecules and Cas9 Polypeptides

Engineered Cas9 molecules and engineered Cas9 polypeptides described herein include a

Cas9 molecule or Cas9 polypeptide comprising a deletion that reduces the size of the molecule while still retaining desired Cas9 properties, e.g., essentially native conformation, Cas9 nuclease activity, and/or target nucleic acid molecule recognition. Provided herein are Cas9 molecules or Cas9 polypeptides comprising one or more deletions and optionally one or more linkers, wherein a linker is disposed between the amino acid residues that flank the deletion. Methods for identifying suitable deletions in a reference Cas9 molecule, methods for generating Cas9 molecules with a deletion and a linker, and methods for using such Cas9 molecules will be apparent to one of ordinary skill in the art upon review of this document.

A Cas9 molecule, e.g., a S. aureus, S. pyogenes, or C. jejuni, Cas9 molecule, having a deletion is smaller, e.g., has reduced number of amino acids, than the corresponding naturally- occurring Cas9 molecule. The smaller size of the Cas9 molecules allows increased flexibility for

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5535.1 delivery methods, and thereby increases utility for genome-editing. A Cas9 molecule or Cas9 polypeptide can comprise one or more deletions that do not substantially affect or decrease the activity of the resultant Cas9 molecules or Cas9 polypeptides described herein. Activities that are retained in the Cas9 molecules or Cas9 polypeptides comprising a deletion as described herein include one or more of the following:

a nickase activity, i.e., the ability to cleave a single strand, e.g., the non-complementary strand or the complementary strand, of a nucleic acid molecule; a double stranded nuclease activity, i.e., the ability to cleave both strands of a double stranded nucleic acid and create a double stranded break, which in an embodiment is the presence of two nickase activities;

an endonuclease activity;

an exonuclease activity;

a helicase activity, i.e., the ability to unwind the helical structure of a double stranded nucleic acid;

and recognition activity of a nucleic acid molecule, e.g., a target nucleic acid or a gRNA. Activity of the Cas9 molecules or Cas9 polypeptides described herein can be assessed using the activity assays described herein or in the art.

Identifying regions suitable for deletion

Suitable regions of Cas9 molecules for deletion can be identified by a variety of methods. Naturally- occurring orthologous Cas9 molecules from various bacterial species, e.g., any one of those listed in Table 50, can be modeled onto the crystal structure of S. pyogenes Cas9

(Nishimasu et al., Cell, 156:935-949, 2014) to examine the level of conservation across the selected Cas9 orthologs with respect to the three-dimensional conformation of the protein. Less conserved or unconserved regions that are spatially located distant from regions involved in Cas9 activity, e.g., interface with the target nucleic acid molecule and/or gRNA, represent regions or domains are candidates for deletion without substantially affecting or decreasing Cas9 activity.

REC-Optimized Cas9 Molecules and Cas9 Polypeptides

A REC-optimized Cas9 molecule, or a REC-optimized Cas9 polypeptide, as that term is used herein, refers to a Cas9 molecule or Cas9 polypeptide that comprises a deletion in one or both of the REC2 domain and the RE1_CT domain (collectively a REC deletion), wherein the

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5535.1 deletion comprises at least 10% of the amino acid residues in the cognate domain. A REC- optimized Cas9 molecule or Cas9 polypeptide can be an eaCas9 molecule or eaCas9 polypetide, or an eiCas9 molecule or eiCas9 polypeptide. An exemplary REC-optimized Cas9 molecule or REC-optimized Cas9 polypeptide comprises:

a) a deletion selected from:

i) a REC2 deletion;

ii) a REC I_CT deletion; or

iii) a REC I_SUB deletion.

Optionally, a linker is disposed between the amino acid residues that flank the deletion. In an embodiment, a Cas9 molecule or Cas9 polypeptide includes only one deletion, or only two deletions. A Cas9 molecule or Cas9 polypeptide can comprise a REC2 deletion and a RECI_CT deletion. A Cas9 molecule or Cas9 polypeptide can comprise a REC2 deletion and a REC I_SUB deletion.

Generally, the deletion will contain at least 10% of the amino acids in the cognate domain, e.g., a REC2 deletion will include at least 10% of the amino acids in the REC2 domain.

A deletion can comprise: at least 10, 20, 30, 40, 50, 60, 70, 80, or 90% of the amino acid residues of its cognate domain; all of the amino acid residues of its cognate domain; an amino acid residue outside its cognate domain; a plurality of amino acid residues outside its cognate domain; the amino acid residue immediately N terminal to its cognate domain; the amino acid residue immediately C terminal to its cognate domain; the amino acid residue immediately N terminal to its cognate and the amino acid residue immediately C terminal to its cognate domain; a plurality of, e.g., up to 5, 10, 15, or 20, amino acid residues N terminal to its cognate domain; a plurality of, e.g., up to 5, 10, 15, or 20, amino acid residues C terminal to its cognate domain; a plurality of, e.g., up to 5, 10, 15, or 20, amino acid residues N terminal to to its cognate domain and a plurality of e.g., up to 5, 10, 15, or 20, amino acid residues C terminal to its cognate domain.

In an embodiment, a deletion does not extend beyond: its cognate domain; the N terminal amino acid residue of its cognate domain; the C terminal amino acid residue of its cognate domain.

A REC-optimized Cas9 molecule or REC-optimized Cas9 polypeptide can include a linker disposed between the amino acid residues that flank the deletion. Any linkers known in

1570

5535.1 the art that maintain the conformation or native fold of the Cas9 molecule (thereby retaining Cas9 activity) can be used between the amino acid resides that flank a REC deletion in a REC- optimized Cas9 molecule or REC-optimized Cas9 polypeptide. Linkers for use in generating recombinant proteins, e.g., multi-domain proteins, are known in the art (Chen et al., Adv Drug Delivery Rev, 65: 1357-69, 2013).

In an embodiment, a REC-optimized Cas9 molecule or REC-optimized Cas9 polypeptide comprises an amino acid sequence that, other than any REC deletion and associated linker, has at least 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 99, or 100% homology with the amino acid sequence of a naturally occurring Cas 9, e.g., a Cas9 molecule described in Table 50, e.g., a S. aureus Cas9 molecule, a S. pyogenes Cas9 molecule, or a C. jejuni Cas9 molecule.

In an embodiment, a a REC-optimized Cas9 molecule or REC-optimized Cas9 polypeptide comprises an amino acid sequence that, other than any REC deletion and associated linker, differs by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, or 25, amino acid residues from the amino acid sequence of a naturally occurring Cas 9, e.g., a Cas9 molecule described in Table 50, e.g., a S. aureus Cas9 molecule, a S. pyogenes Cas9 molecule, or a C. jejuni Cas9 molecule.

In an embodiment, a REC-optimized Cas9 molecule or REC-optimized Cas9 polypeptide comprises an amino acid sequence that, other than any REC deletion and associate linker, differs by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, or 25% of the, amino acid residues from the amino acid sequence of a naturally occurring Cas 9, e.g., a Cas9 molecule described in Table 50, e.g., a S. aureus Cas9 molecule, a S. pyogenes Cas9 molecule, or a C. jejuni Cas9 molecule.

For sequence comparison, typically one sequence acts as a reference sequence, to which test sequences are compared. When using a sequence comparison algorithm, test and reference sequences are entered into a computer, subsequence coordinates are designated, if necessary, and sequence algorithm program parameters are designated. Default program parameters can be used, or alternative parameters can be designated. The sequence comparison algorithm then calculates the percent sequence identities for the test sequences relative to the reference sequence, based on the program parameters. Methods of alignment of sequences for comparison are well known in the art. Optimal alignment of sequences for comparison can be conducted, e.g., by the local homology algorithm of Smith and Waterman, (1970) Adv. Appl. Math. 2:482c, by the homology alignment algorithm of Needleman and Wunsch, (1970) J. Mol. Biol. 48:443, by the search for similarity method of Pearson and Lipman, (1988) Proc. Nat'l. Acad. Sci. USA

1571

5535.1 85:2444, by computerized implementations of these algorithms (GAP, BESTFIT, FASTA, and TFASTA in the Wisconsin Genetics Software Package, Genetics Computer Group, 575 Science Dr., Madison, WI), or by manual alignment and visual inspection (see, e.g., Brent et al., (2003) Current Protocols in Molecular Biology).

Two examples of algorithms that are suitable for determining percent sequence identity and sequence similarity are the BLAST and BLAST 2.0 algorithms, which are described in Altschul et al., (1977) Nuc. Acids Res. 25:3389-3402; and Altschul et al., (1990) J. Mol. Biol. 215:403-410, respectively. Software for performing BLAST analyses is publicly available through the National Center for Biotechnology Information.

The percent identity between two amino acid sequences can also be determined using the algorithm of E. Meyers and W. Miller, (1988) Comput. Appl. Biosci. 4: 11-17) which has been incorporated into the ALIGN program (version 2.0), using a PAM120 weight residue table, a gap length penalty of 12 and a gap penalty of 4. In addition, the percent identity between two amino acid sequences can be determined using the Needleman and Wunsch (1970) J. Mol. Biol.

48:444-453) algorithm which has been incorporated into the GAP program in the GCG software package (available at www.gcg.com), using either a Blossom 62 matrix or a PAM250 matrix, and a gap weight of 16, 14, 12, 10, 8, 6, or 4 and a length weight of 1, 2, 3, 4, 5, or 6.

Sequence information for exemplary REC deletions are provided for 83 naturally- occurring Cas9 orthologs in Table 50.

The amino acid sequences of exemplary Cas9 molecules from different bacterial species are shown below.

Table 50. Amino Acid Sequence of Cas9 Orthologs

1572

5535.1 Bifidobacterium bifidum S 17 SEQ ID NO: 173 335 163 516 607 87 516 607 87 gil310286728 Iref 1 YP_003937986 308

Veillonella atypica ACS-134-V- SEQ ID NO: 185 339 155 574 663 79 574 663 79

Col7a 309

gil303229466lreflZP_07316256.1

Lactobacillus rhamnosus GG SEQ ID NO: 169 320 152 559 645 78 559 645 78 gil258509199lreflYP_003171950 310

.1

Filifactor alocis ATCC 35896 SEQ ID NO: 166 314 149 508 592 76 508 592 76 gil374307738lreflYP_005054169 311

.1

Oenococcus kitaharae DSM SEQ ID NO: 169 317 149 555 639 80 555 639 80

17330 312

gil366983953lgblEHN59352.1l

Fructobacillus fructosus KCTC SEQ ID NO: 168 314 147 488 571 76 488 571 76

3544 313

gil339625081 lreflZP_08660870.1

Catenibacterium mitsuokai DSM SEQ ID NO: 173 318 146 511 594 78 511 594 78

15897 314

gil224543312lreflZP_03683851.1

Finegoldia magna ATCC 29328 SEQ ID NO: 168 313 146 452 534 77 452 534 77 gill69823755lreflYP_001691366 315

.1

CoriobacteriumglomeransPW2 SEQ ID NO: 175 318 144 511 592 82 511 592 82 gil328956315lreflYP_004373648 316

.1

Eubacterium yurii ATCC 43715 SEQ ID NO: 169 310 142 552 633 76 552 633 76 gil306821691 lreflZP_07455288.1 317

Peptoniphilus duerdenii ATCC SEQ ID NO: 171 311 141 535 615 76 535 615 76 BAA- 1640 318

gil304438954lreflZP_07398877.1

Acidaminococcus sp. D21 SEQ ID NO: 167 306 140 511 591 75 511 591 75 gil227824983lreflZP_03989815.1 319

Lactobacillus farciminis KCTC SEQ ID NO: 171 310 140 542 621 85 542 621 85

3681 320

gil336394882lreflZP_08576281.1

Streptococcus sanguinis SK49 SEQ ID NO: 185 324 140 411 490 85 411 490 85 gil422884106lreflZP_l 6930555.1 321

Coprococcus catus GD-7 SEQ ID NO: 172 310 139 556 634 76 556 634 76 gil291520705lemblCBK78998.1 l 322

Streptococcus mutans UA159 SEQ ID NO: 176 314 139 392 470 84 392 470 84 gil24379809lreflNP_721764.11 323

Streptococcus pyogenes Ml SEQ ID NO: 176 314 139 523 600 82 523 600 82

GAS 324

gill3622193lgblAAK33936.1 l

Streptococcus thermophilus SEQ ID NO: 176 314 139 481 558 81 481 558 81 LMD-9 325

gil 1 16628213 Iref 1 YP_820832.11

1573

5535.1 Fusobacteriumnucleatum SEQ ID NO: 171 308 138 537 614 76 537 614 76 ATCC49256 326

gil34762592lreflZP_00143587.1 l

Planococcus antarcticus DSM SEQ ID NO: 162 299 138 538 614 94 538 614 94

14505 327

gil389815359lreflZP_10206685.1

Treponema denticola ATCC SEQ ID NO: 169 305 137 524 600 81 524 600 81

35405 328

gil42525843lreflNP_970941.11

Solobacterium moorei F0204 SEQ ID NO: 179 314 136 544 619 77 544 619 77 gil320528778lreflZP_08029929.1 329

Staphylococcus SEQ ID NO: 164 299 136 531 606 92 531 606 92 pseudintermedius ED99 330

gil323463801 lgblADX75954.11

Flavobacterium branchiophilum SEQ ID NO: 162 286 125 538 613 63 538 613 63

FL-15 331

gil347536497lreflYP_004843922

.1

Ignavibacterium album JCM SEQ ID NO: 223 329 107 357 432 90 357 432 90

16511 332

gil38581 1609lreflYP_005848005

.1

Bergeyella zoohelcum ATCC SEQ ID NO: 165 261 97 529 604 56 529 604 56

43767 333

gi 1423317190lref IZP_ 17295095.1

Nitrobacter hamburgensis X14 SEQ ID NO: 169 253 85 536 611 48 536 611 48 gil92109262lrefl YP_571550.11 334

Odoribacter laneus YIT 12061 SEQ ID NO: 164 242 79 535 610 63 535 610 63 gil374384763lreflZP_09642280.1 335

Legionella pneumophila str. SEQ ID NO: 164 239 76 402 476 67 402 476 67

Paris 336

gil54296138lreflYP_122507.1 l

Bacteroides sp. 20 3 SEQ ID NO: 198 269 72 530 604 83 530 604 83 gi 130131 1869 Iref IZP_07217791.1 337

Akkermansia muciniphila ATCC SEQ ID NO: 136 202 67 348 418 62 348 418 62

BAA-835 338

gill87736489lreflYP_001878601

Prevotella sp. C561 SEQ ID NO: 184 250 67 357 425 78 357 425 78 gil345885718lreflZP_08837074.1 339

Wolinella succinogenes DSM SEQ ID NO: 157 218 36 401 468 60 401 468 60

1740 340

gil34557932lreflNP_907747.11

Alicyclobacillus hesperidum SEQ ID NO: 142 196 55 416 482 61 416 482 61 URH17-3-68 341

gil403744858lreflZP_10953934.1

Caenispirillum salinarum AK4 SEQ ID NO: 161 214 54 330 393 68 330 393 68 gil427429481 lreflZP_l 891951 1.1 342

Eubacterium rectale ATCC SEQ ID NO: 133 185 53 322 384 60 322 384 60 33656 343

gil238924075lreflYP_002937591

.1

1574

5535.1 Mycoplasma synoviae 53 SEQ ID NO: 187 239 53 319 381 80 319 381 80 gil71894592lref 1 YP_278700.11 344

Porphyromonas sp. oral taxon SEQ ID NO: 150 202 53 309 371 60 309 371 60 279 str. F0450 345

gil402847315 Iref IZP_10895610.1

Streptococcus thermophilus SEQ ID NO: 127 178 139 424 486 81 424 486 81 LMD-9 346

gil 116627542lref 1 YP_820161.11

Roseburia inulinivorans DSM SEQ ID NO: 154 204 51 318 380 69 318 380 69

16841 347

gil225377804lreflZP_03755025.1

Methylosinus trichosporium SEQ ID NO: 144 193 50 426 488 64 426 488 64

OB3b 348

gil296446027lreflZP_06887976.1

Ruminococcus albus 8 SEQ ID NO: 139 187 49 351 412 55 351 412 55 gil325677756lreflZP_08157403.1 349

Bifidobacterium longum SEQ ID NO: 183 230 48 370 431 44 370 431 44 DJO10A 350

gill89440764lreflYP_001955845

Enterococcus faecalis TX0012 SEQ ID NO: 123 170 48 327 387 60 327 387 60 gil315149830lgblEFT93846.11 351

Mycoplasma mobile 163K SEQ ID NO: 179 226 48 314 374 79 314 374 79 gil47458868lreflYP_015730.1 l 352

Actinomyces coleocanis DSM SEQ ID NO: 147 193 47 358 418 40 358 418 40

15436 353

gil227494853lreflZP_03925169.1

Dinoroseobacter shibae DFL 12 SEQ ID NO: 138 184 47 338 398 48 338 398 48 gil 159042956lref 1 YP_001531750 354

.1

Actinomyces sp. oral taxon 180 SEQ ID NO: 183 228 46 349 409 40 349 409 40 str. F0310 355

gil315605738lreflZP_07880770.1

Alcanivorax sp. Wl 1-5 SEQ ID NO: 139 183 45 344 404 61 344 404 61 gil407803669lreflZP_l 1150502.1 356

Aminomonas paucivorans DSM SEQ ID NO: 134 178 45 341 401 63 341 401 63

12260 357

gi 1312879015 Iref IZP_07738815.1

Mycoplasma canis PG 14 SEQ ID NO: 139 183 45 319 379 76 319 379 76 gil384393286lgblEIE39736.11 358

Lactobacillus coryniformis SEQ ID NO: 141 184 44 328 387 61 328 387 61 KCTC 3535 359

gil336393381 lreflZP_08574780.1

Elusimicrobium minutum Peil91 SEQ ID NO: 177 219 43 322 381 47 322 381 47 gill87250660lreflYP_001875142 360

.1

Neisseria meningitidis Z2491 SEQ ID NO: 147 189 43 360 419 61 360 419 61 gil218767588lreflYP_002342100 361

.1

Pasteurella multocida str. Pm70 SEQ ID NO: 139 181 43 319 378 61 319 378 61 gill5602992lreflNP_246064.11 362

1575

5535.1 Rhodovulum sp. PH10 SEQ ID NO: 141 183 43 319 378 48 319 378 48 gil402849997lreflZP_10898214.1 363

Eubacterium dolichum DSM SEQ ID NO: 131 172 42 303 361 59 303 361 59

3991 364

gill60915782lreflZP_02077990.1

Nitratifractor salsuginis DSM SEQ ID NO: 143 184 42 347 404 61 347 404 61

16511 365

gil319957206lreflYP_004168469

.1

Rhodospirillum rubrum ATCC SEQ ID NO: 139 180 42 314 371 55 314 371 55

11170 366

gil83591793lreflYP_425545.1 l

Clostridium cellulolyticum H10 SEQ ID NO: 137 176 40 320 376 61 320 376 61 gil220930482lreflYP_002507391 367

.1

Helicobacter mustelae 12198 SEQ ID NO: 148 187 40 298 354 48 298 354 48 gi 1291276265 Iref 1 YP_003516037 368

.1

Ilyobacter polytropus DSM 2926 SEQ ID NO: 134 173 40 462 517 63 462 517 63 gil310780384lref 1 YP_003968716 369

.1

Sphaerochaeta globus str. Buddy SEQ ID NO: 163 202 40 335 389 45 335 389 45 gil325972003lreflYP_004248194 370

.1

Staphylococcus lugdunensis SEQ ID NO: 128 167 40 337 391 57 337 391 57 M23590 371

gil315659848lreflZP_07912707.1

Treponema sp. JC4 SEQ ID NO: 144 183 40 328 382 63 328 382 63 gil384109266lreflZP_10010146.1 372

uncultured delta proteobacterium SEQ ID NO: 154 193 40 313 365 55 313 365 55 HF0070 07E19 373

gi 1297182908 Igb 1 ADI 19058.11

Alicycliphilus denitrificans K601 SEQ ID NO: 140 178 39 317 366 48 317 366 48 gil330822845lreflYP_004386148 374

.1

Azospirillum sp. B510 SEQ ID NO: 205 243 39 342 389 46 342 389 46 gil288957741 lreflYP_003448082 375

.1

Bradyrhizobium sp. BTAil SEQ ID NO: 143 181 39 323 370 48 323 370 48 gill48255343lreflYP_001239928 376

.1

Parvibaculum lavamentivorans SEQ ID NO: 138 176 39 327 374 58 327 374 58

DS-1 377

gill54250555lreflYP_001411379

.1

Prevotella timonensis CRIS 5C- SEQ ID NO: 170 208 39 328 375 61 328 375 61

B l 378

gil282880052lreflZP_06288774.1

Bacillus smithii 7 3 47FAA SEQ ID NO: 134 171 38 401 448 63 401 448 63 gil365156657lreflZP_09352959.1 379

Cand. Puniceispirillum marinum SEQ ID NO: 135 172 38 344 391 53 344 391 53 IMCC1322 380

1576

5535.1 gil2940861 1 l lreflYP_003552871

.1

Barnesiella intestinihominis YIT SEQ ID NO: 140 176 37 371 417 60 371 417 60

1 1860 381

gi|404487228lreflZP_l 1022414.1

Ralstonia syzygii R24 SEQ ID NO: 140 176 37 395 440 50 395 440 50 gil344171927lemblCCA84553.1 l 382

Wolinella succinogenes DSM SEQ ID NO: 145 180 36 348 392 60 348 392 60

1740 383

gil34557790lreflNP_907605.11

Mycoplasma gallisepticum str. F SEQ ID NO: 144 177 34 373 416 71 373 416 71 gi 128493171 Olgb IADC31648.11 384

Acidothermus cellulolyticus 1 IB SEQ ID NO: 150 182 33 341 380 58 341 380 58 gil 1 17929158 Irefl YP_873709.11 385

Mycoplasma ovipneumoniae SEQ ID NO: 156 184 29 381 420 62 381 420 62

SCOl 386

gil363542550lreflZP_09312133.1

1577

5535.1 Table 51. Amino Acid Sequence of Cas9 Core Domains

Table 52. Identified PAM sequences and corresponding RKR motifs.

PI domains are provided in Tables 53 and 54.

Table 53. Altered PI Domains

Table 50

Akkermansia muciniphila ATCC BAA-835 871 1101 231 ALK

Ralstonia syzygii R24 821 1062 242 APY

Cand. Puniceispirillum marinum IMCC1322 815 1035 221 AYK

Fructobacillus fructosus KCTC 3544 1074 1323 250 DON

Eubacterium yurii ATCC 43715 1107 1391 285 DGY

Eubacterium dolichum DSM 3991 779 1096 318 DKK

Dinoroseobacter shibae DFL 12 851 1079 229 DPI

Clostridium cellulolyticum H10 767 1021 255 EGK

Pasteurella multocida str. Pm70 815 1056 242 EN

Mycoplasma canis PG 14 907 1233 327 EPK

Porphyromonas sp. oral taxon 279 str. F0450 935 1197 263 EPT

Filifactor alocis ATCC 35896 1094 1365 272 EVD

Aminomonas paucivorans DSM 12260 801 1052 252 EVY

Wolinella succinogenes DSM 1740 1034 1409 376 EYK

Oenococcus kitaharae DSM 17330 1119 1389 271 GAL

CoriobacteriumglomeransPW2 1126 1384 259 GDR

Peptoniphilus duerdenii ATCC BAA-1640 1091 1364 274 GDS

Bifidobacterium bifidum S17 1138 1420 283 GGL

Alicyclobacillus hesperidum URH17-3-68 876 1146 271 GGR

Roseburia inulinivorans DSM 16841 895 1152 258 GGT

Actinomyces coleocanis DSM 15436 843 1105 263 GKK

Odoribacter laneus YIT 12061 1103 1498 396 GKV

Coprococcus catus GD-7 1063 1338 276 GNQ

Enterococcus faecalis TX0012 829 1150 322 GRK

Bacillus smithii 7 3 47FAA 809 1088 280 GSK

Legionella pneumophila str. Paris 1021 1372 352 GTM

Bacteroides fragilis NCTC 9343 1140 1436 297 IPV

Mycoplasma ovipneumoniae SCOl 923 1265 343 IRI

Actinomyces sp. oral taxon 180 str. F0310 895 1181 287 KEK

Treponema sp. JC4 832 1062 231 KIS

Fusobacteriumnucleatum ATCC49256 1073 1374 302 KKV

Lactobacillus farciminis KCTC 3681 1101 1356 256 KKV

Nitratifractor salsuginis DSM 16511 840 1132 293 KMR

Lactobacillus coryniformis KCTC 3535 850 1119 270 KNK

Mycoplasma mobile 163K 916 1236 321 KNY

Flavobacterium branchiophilum FL-15 1182 1473 292 KQK

Prevotella timonensis CRIS 5C-B1 957 1218 262 KQQ

Methylosinus trichosporium OB3b 830 1082 253 KRP Prevotella sp. C561 1099 1424 326 KRY

Mycoplasma gallisepticum str. F 911 1269 359 KTA

Lactobacillus rhamnosus GG 1077 1363 287 KYG

Wolinella succinogenes DSM 1740 811 1059 249 LPN

Streptococcus thermophilus LMD-9 1099 1388 290 MLA

Treponema denticola ATCC 35405 1092 1395 304 NDS

Bergeyella zoohelcum ATCC 43767 1098 1415 318 NEK

Veillonella atypica ACS-134-V-Col7a 1107 1398 292 NGF

Neisseria meningitidis Z2491 835 1082 248 NHN

Ignavibacterium album JCM 16511 1296 1688 393 NKK

Ruminococcus albus 8 853 1156 304 NNF

Streptococcus thermophilus LMD-9 811 1121 311 N K

Barnesiella intestinihominis YIT 11860 871 1153 283 NPV

Azospirillum sp. B510 911 1168 258 PFH

Rhodospirillum rubrum ATCC 11170 863 1173 311 PRG

Planococcus antarcticus DSM 14505 1087 1333 247 PYY

Staphylococcus pseudintermedius ED99 1073 1334 262 QIV

Alcanivorax sp. Wl l-5 843 1113 271 RIE

Bradyrhizobium sp. BTAil 811 1064 254 RIY

Streptococcus pyogenes Ml GAS 1099 1368 270 RKR

Streptococcus mutans UA159 1078 1345 268 RKR

Streptococcus Pyogenes 1099 1368 270 RKR

Bacteroides sp. 20 3 1147 1517 371 RNI

S. aureus 772 1053 282 RNK

Solobacterium moorei F0204 1062 1327 266 RSG

Finegoldia magna ATCC 29328 1081 1348 268 RTE uncultured delta proteobacterium HF0070 07E19 770 1011 242 SGG

Acidaminococcus sp. D21 1064 1358 295 SIG

Eubacterium rectale ATCC 33656 824 1114 291 SKK

Caenispirillum salinarum AK4 1048 1442 395 SLV

Acidothermus cellulolyticus 11B 830 1138 309 SPS

Catenibacterium mitsuokai DSM 15897 1068 1329 262 SPT

Parvibaculum lavamentivorans DS-1 827 1037 211 TGN

Staphylococcus lugdunensis M23590 772 1054 283 TKK

Streptococcus sanguinis SK49 1123 1421 299 TRM

Elusimicrobium minutum Peil91 910 1195 286 TTG

Nitrobacter hamburgensis X14 914 1166 253 VAY

Mycoplasma synoviae 53 991 1314 324 VGF

Sphaerochaeta globus str. Buddy 877 1179 303 VKG Ilyobacter polytropus DSM 2926 837 1092 256 VNG

Rhodovulum sp. PH10 821 1059 239 VPY

Bifidobacterium longum DJOIOA 904 1187 284 VRK

Amino acid sequences described in Table 50:

SEQ ID NO: 304

MKRNYILGLDIGITSVGYGI IDYETRDVIDAGVRLFKEANVENNEGRRSKRGARRLKRRRRHRI QRVKKLLFDYNLLTDHSELSGINPYEARVKGLSQKLSEEEFSAALLHLAKRRGVHNVNEVEEDT GNELSTKEQI SRNSKALEEKYVAELQLERLKKDGEVRGS INRFKTSDYVKEAKQLLKVQKAYHQ LDQSFIDTYIDLLETRRTYYEGPGEGSPFGWKDIKEWYEMLMGHCTYFPEELRSVKYAYNADLY NALNDLNNLVITRDENEKLEYYEKFQI IENVFKQKKKPTLKQIAKEILVNEEDIKGYRVTSTGK PEFTNLKVYHDIKDITARKEI IENAELLDQIAKILTIYQSSEDIQEELTNLNSELTQEEIEQIS NLKGYTGTHNLSLKAINLILDELWHTNDNQIAIFNRLKLVPKKVDLSQQKEIPTTLVDDFILSP VVKRSFIQS IKVINAI IKKYGLPNDI I IELAREKNSKDAQKMINEMQKRNRQTNERIEEI IRTT GKENAKYLIEKIKLHDMQEGKCLYSLEAIPLEDLLNNPFNYEVDHI IPRSVSFDNSFNNKVLVK QEENSKKGNRTPFQYLSSSDSKI SYETFKKHILNLAKGKGRI SKTKKEYLLEERDINRFSVQKD FINRNLVDTRYATRGLMNLLRSYFRVNNLDVKVKS INGGFTSFLRRKWKFKKERNKGYKHHAED ALI IA ADFIFKEWKKLDKAKKVMENQMFEEKQAESMPEIETEQEYKEIFITPHQIKHIKDFKD YKYSHRVDKKPNRELINDTLYSTRKDDKGNTLIVNNLNGLYDKDNDKLKKLINKSPEKLLMYHH DPQTYQKLKLIMEQYGDEKNPLYKYYEETGNYLTKYSKKDNGPVIKKIKYYGNKLNAHLDITDD YPNSRNKVVKLSLKPYRFDVYLDNGVYKFVTVKNLDVIKKENYYEVNSKCYEEAKKLKKISNQA EFIASFYNNDLIKINGELYRVIGVNNDLLNRIEVNMIDITYREYLENMNDKRPPRI IKTIASKT QS IKKYSTDILGNLYEVKSKKHPQI IKKG

SEQ ID NO: 305

MDKKYS IGLDIGTNSVGWAVITDEYKVPSKKFKVLGNTDRHS IKKNLIGALLFDSGETAEATRL KRTARRRYTRRKNRICYLQEIFSNEMAKVDDSFFHRLEESFLVEEDKKHERHPIFGNIVDEVAY HEKYPTIYHLRKKLVDSTDKADLRLIYLALAHMIKFRGHFLIEGDLNPDNSDVDKLFIQLVQTY NQLFEENPINASGVDAKAILSARLSKSRRLENLIAQLPGEKKNGLFGNLIALSLGLTPNFKSNF DLAEDAKLQLSKDTYDDDLDNLLAQIGDQYADLFLAAKNLSDAILLSDILRVNTEITKAPLSAS MIKRYDEHHQDLTLLKALVRQQLPEKYKEIFFDQSKNGYAGYIDGGASQEEFYKFIKPILEKMD GTEELLVKLNREDLLRKQRTFDNGS IPHQIHLGELHAILRRQEDFYPFLKDNREKIEKILTFRI PYYVGPLARGNSRFAWMTRKSEETITPWNFEEVVDKGASAQSFIERMTNFDKNLPNEKVLPKHS LLYEYFTVYNELTKVKYVTEGMRKPAFLSGEQKKAIVDLLFKTNRKVTVKQLKEDYFKKIECFD SVEI SGVEDRFNASLGTYHDLLKI IKDKDFLDNEENEDILEDIVLTLTLFEDREMIEERLKTYA HLFDDKVMKQLKRRRYTGWGRLSRKLINGIRDKQSGKTILDFLKSDGFANRNFMQLIHDDSLTF KEDIQKAQVSGQGDSLHEHIANLAGSPAIKKGILQTVKVVDELVKVMGRHKPENIVIEMARENQ TTQKGQKNSRERMKRIEEGIKELGSQILKEHPVENTQLQNEKLYLYYLQNGRDMYVDQELDINR LSDYDVDHIVPQSFLKDDS IDNKVLTRSDKNRGKSDNVPSEEVVKKMKNYWRQLLNAKLITQRK FDNLTKAERGGLSELDKAGFIKRQLVETRQITKHVAQILDSRMNTKYDENDKLIREVKVITLKS KLVSDFRKDFQFYKVREINNYHHAHDAYLNAVVGTALIKKYPKLESEFVYGDYKVYDVRKMIAK SEQEIGKATAKYFFYSNIMNFFKTEITLANGEIRKRPLIETNGETGEIVWDKGRDFATVRKVLS MPQVNIVKKTEVQTGGFSKES ILPKRNSDKLIARKKDWDPKKYGGFDSPTVAYSVLVVAKVEKG KSKKLKSVKELLGITIMERSSFEKNPIDFLEAKGYKEVKKDLI IKLPKYSLFELENGRKRMLAS AGELQKGNELALPSKYVNFLYLASHYEKLKGSPEDNEQKQLFVEQHKHYLDEI IEQI SEFSKRV ILADANLDKVLSAYNKHRDKPIREQAE I IHLFTLTNLGAPAAFKYFDTTIDRKRYTSTKEVLD ATLIHQS ITGLYETRIDLSQLGGD

SEQ ID NO: 306

MARILAFDIGI SS IGWAFSENDELKDCGVRIFTKVENPKTGESLALPRRLARSARKRLARRKAR LNHLKHLIANEFKLNYEDYQSFDESLAKAYKGSLI SPYELRFRALNELLSKQDFARVILHIAKR RGYDDIKNSDDKEKGAILKAIKQNEEKLANYQSVGEYLYKEYFQKFKENSKEFTNVRNKKESYE RCIAQSFLKDELKLIFKKQREFGFSFSKKFEEEVLSVAFYKRALKDFSHLVGNCSFFTDEKRAP KNSPLAFMFVALTRI INLLNNLKNTEGILYTKDDLNALLNEVLKNGTLTYKQTKKLLGLSDDYE FKGEKGTYFIEFKKYKEFIKALGEHNLSQDDLNEIAKDITLIKDEIKLKKALAKYDLNQNQIDS LSKLEFKDHL I SFKALKLVTPLMLEGKKYDEACNELNLKVAINEDKKDFLPAFNETYYKDEVT NPVVLRAIKEYRKVLNALLKKYGKVHKINIELAREVGKNHSQRAKIEKEQNENYKAKKDAELEC EKLGLKINSKNILKLRLFKEQKEFCAYSGEKIKI SDLQDEKMLEIDHIYPYSRSFDDSYMNKVL VFTKQNQEKLNQTPFEAFGNDSAKWQKIEVLAKNLPTKKQKRILDKNYKDKEQKNFKDRNLNDT RYIARLVLNYTKDYLDFLPLSDDENTKLNDTQKGSKVHVEAKSGMLTSALRHTWGFSAKDRNNH LHHAIDAVI IAYANNS IVKAFSDFKKEQESNSAELYAKKI SELDYKNKRKFFEPFSGFRQKVLD KIDEIFVSKPERKKPSGALHEETFRKEEEFYQSYGGKEGVLKALELGKIRKVNGKIVKNGDMFR VDIFKHKKTNKFYAVPIYTMDFALKVLPNKAVARSKKGEIKDWILMDENYEFCFSLYKDSLILI QTKDMQEPEFVYY AFTSSTVSLIVSKHDNKFETLSKNQKILFKNANEKEVIAKS IGIQNLKVF EKYIVSALGEVTKAEFRQREDFKK

SEQ ID NO: 307

MKRILGLDLGTNS IGWALVNEAENKDERSS IVKLGVRVNPLTVDELTNFEKGKS ITTNADRTLK RGMRRNLQRYKLRRETLTEVLKEHKLITEDTILSENGNRTTFETYRLRAKAVTEEI SLEEFARV LLMINKKRGYKSSRKAKGVEEGTLIDGMDIARELYNNNLTPGELCLQLLDAGKKFLPDFYRSDL QNELDRIWEKQKEYYPEILTDVLKEELRGKKRDAVWAICAKYFVWKENYTEWNKEKGKTEQQER EHKLEGIYSKRKRDEAKRENLQWRVNGLKEKLSLEQLVIVFQEMNTQINNSSGYLGAI SDRSKE LYFNKQTVGQYQMEMLDKNPNASLRNMVFYRQDYLDEFNMLWEKQAVYHKELTEELKKEIRDI I IFYQRRLKSQKGLIGFCEFESRQIEVDIDGKKKIKTVGNRVI SRSSPLFQEFKIWQILNNIEVT VVGKKRKRRKLKENYSALFEELNDAEQLELNGSRRLCQEEKELLAQELFIRDKMTKSEVLKLLF DNPQELDLNFKTIDGNKTGYALFQAYSKMIEMSGHEPVDFKKPVEKVVEYIKAVFDLLNWNTDI LGFNSNEELDNQPYYKLWHLLYSFEGDNTPTGNGRLIQKMTELYGFEKEYATILANVSFQDDYG SLSAKAIHKILPHLKEGNRYDVACVYAGYRHSESSLTREEIANKVLKDRLMLLPKNSLHNPVVE KILNQMVNVINVI IDIYGKPDEIRVELARELKKNAKEREELTKS IAQTTKAHEEYKTLLQTEFG LTNVSRTDILRYKLYKELESCGYKTLYSNTYI SREKLFSKEFDIEHI IPQARLFDDSFSNKTLE ARSVNIEKGNKTAYDFVKEKFGESGADNSLEHYLNNIEDLFKSGKI SKTKYNKLKMAEQDIPDG FIERDLRNTQYIAKKALSMLNEI SHRVVATSGSVTDKLREDWQLIDVMKELNWEKYKALGLVEY FEDRDGRQIGRIKDWTKRNDHRHHAMDALTVAFTKDVFIQYFNNKNASLDPNANEHAIKNKYFQ NGRAIAPMPLREFRAEAKKHLENTLI S IKAKNKVITGNINKTRKKGGVNKNMQQTPRGQLHLET IYGSGKQYLTKEEKVNASFDMRKIGTVSKSAYRDALLKRLYENDNDPKKAFAGKNSLDKQPIWL DKEQMRKVPEKVKIVTLEAIYTIRKEI SPDLKVDKVIDVGVRKILIDRLNEYGNDAKKAFSNLD KNPIWLNKEKGI S IKRVTI SGI SNAQSLHVKKDKDGKPILDENGRNIPVDFVNTGNNHHVAVYY RPVIDKRGQLVVDEAGNPKYELEEVVVSFFEAVTRANLGLPI IDKDYKTTEGWQFLFSMKQNEY FVFPNEKTGFNPKEIDLLDVENYGLISPNLFRVQKFSLKNYVFRHHLETTIKDTSSILRGITWI DFRSSKGLDTIVKVRVNHIGQIVSVGEY

SEQ ID NO: 308 MSRKNYVDDYAI SLDIGNASVGWSAFTPNYRLVRAKGHELIGVRLFDPADTAESRRMARTTRRR YSRRRWRLRLLDALFDQALSEIDPSFLARRKYSWVHPDDENNADCWYGSVLFDSNEQDKRFYEK YPTIYHLRKALMEDDSQHDIREIYLAIHHMVKYRGNFLVEGTLESSNAFKEDELLKLLGRITRY EMSEGEQNSDIEQDDENKLVAPANGQLADALCATRGSRSMRVDNALEALSAVNDLSREQRAIVK AIFAGLEGNKLDLAKIFVSKEFSSENKKILGIYFNKSDYEEKCVQIVDSGLLDDEEREFLDRMQ GQYNAIALKQLLGRSTSVSDSKCASYDAHRANWNLIKLQLRTKENEKDINENYGILVGWKIDSG QRKSVRGESAYENMRKKANVFFKKMIETSDLSETDKNRLIHDIEEDKLFPIQRDSDNGVIPHQL HQNELKQI IKKQGKYYPFLLDAFEKDGKQINKIEGLLTFRVPYFVGPLVVPEDLQKSDNSENHW MVRKKKGEITPWNFDEMVDKDASGRKFIERLVGTDSYLLGEPTLPKNSLLYQEYEVLNELNNVR LSVRTGNHWNDKRRMRLGREEKTLLCQRLFMKGQTVTKRTAENLLRKEYGRTYELSGLSDESKF TSSLSTYGKMCRIFGEKYVNEHRDLMEKIVELQTVFEDKETLLHQLRQLEGI SEADCALLVNTH YTGWGRLSRKLLTTKAGECKI SDDFAPRKHS I IEIMRAEDRNLMEI ITDKQLGFSDWIEQENLG AENGSSLMEVVDDLRVSPKVKRGI IQS IRLIDDI SKAVGKRPSRIFLELADDIQPSGRTI SRKS RLQDLYRNANLGKEFKGIADELNACSDKDLQDDRLFLYYTQLGKDMYTGEELDLDRLSSAYDID HI IPQAVTQNDS IDNRVLVARAENARKTDSFTYMPQIADRMRNFWQILLDNGLI SRVKFERLTR QNEFSEREKERFVQRSLVETRQIMKNVATLMRQRYGNSAAVIGLNAELTKEMHRYLGFSHKNRD INDYHHAQDALCVGIAGQFAANRGFFADGEVSDGAQNSYNQYLRDYLRGYREKLSAEDRKQGRA FGFIVGSMRSQDEQKRVNPRTGEVVWSEEDKDYLRKVMNYRKMLVTQKVGDDFGALYDETRYAA TDPKGIKGIPFDGAKQDTSLYGGFSSAKPAYAVLIESKGKTRLVNVTMQEYSLLGDRPSDDELR KVLAKKKSEYAKANILLRHVPKMQLIRYGGGLMVIKSAGELNNAQQLWLPYEEYCYFDDLSQGK GSLEKDDLKKLLDS ILGSVQCLYPWHRFTEEELADLHVAFDKLPEDEKKNVITGIVSALHADAK TANLS IVGMTGSWRRMNNKSGYTFSDEDEFIFQSPSGLFEKRVTVGELKRKAKKEVNSKYRTNE KRLPTLSGASQP

SEQ ID NO: 309

METQTSNQLITSHLKDYPKQDYFVGLDIGTNSVGWAVTNTSYELLKFHSHKMWGSRLFEEGESA VTRRGFRSMRRRLERRKLRLKLLEELFADAMAQVDSTFFIRLHESKYHYEDKTTGHSSKHILFI DEDYTDQDYFTEYPTIYHLRKDLMENGTDDIRKLFLAVHHILKYRGNFLYEGATFNSNAFTFED VLKQALV ITFNCFDTNSAI SS I S ILMESGKTKSDKAKAIERLVDTYTVFDEVNTPDKPQKEQ VKEDKKTLKAFANLVLGLSANLIDLFGSVEDIDDDLKKLQIVGDTYDEKRDELAKVWGDEIHI I DDCKSVYDAI ILMS IKEPGLTI SQSKVKAFDKHKEDLVILKSLLKLDRNVYNEMFKSDKKGLHN YVHYIKQGRTEETSCSREDFYKYTKKIVEGLADSKDKEYILNEIELQTLLPLQRIKDNGVIPYQ LHLEELKVILDKCGPKFPFLHTVSDGFSVTEKLIKMLEFRIPYYVGPLNTHHNIDNGGFSWAVR KQAGRVTPWNFEEKIDREKSAAAFIKNLTNKCTYLFGEDVLPKSSLLYSEFMLLNELNNVRIDG KALAQGVKQHLIDSIFKQDHKKMTKNRIELFLKDNNYITKKHKPEITGLDGEIKNDLTSYRDMV RILGNNFDVSMAEDI ITDITIFGESKKMLRQTLRNKFGSQLNDETIKKLSKLRYRDWGRLSKKL LKGIDGCDKAGNGAPKTI IELMRNDSYNLMEILGDKFSFMECIEEENAKLAQGQVVNPHDI IDE LALSPAVKRAVWQALRIVDEVAHIKKALPSRIFVEVARTNKSEKKKKDSRQKRLSDLYSAIKKD DVLQSGLQDKEFGALKSGLANYDDAALRSKKLYLYYTQMGRCAYTG I IDLNQLNTDNYDIDHI YPRSLTKDDSFDNLVLCERTA AKKSDIYPIDNRIQTKQKPFWAFLKHQGLI SERKYERLTRIA PLTADDLSGFIARQLVETNQSVKATTTLLRRLYPDIDVVFVKAENVSDFRHNNNFIKVRSLNHH HHAKDAYLNIVVGNVYHEKFTRNFRLFFKKNGANRTYNLAKMFNYDVICTNAQDGKAWDVKTSM NTVKKMMASNDVRVTRRLLEQSGALADATIYKASVAAKAKDGAYIGMKTKYSVFADVTKYGGMT KIKNAYS I IVQYTGKKGEEIKEIVPLPIYLINRNATDIELIDYVKSVIPKAKDI S IKYRKLCIN QLVKVNGFYYYLGGKTNDKIYIDNAIELVVPHDIATYIKLLDKYDLLRKENKTLKASS ITTS IY INTSTVVSLNKVGIDVFDYFMSKLRTPLYMKMKGNKVDELSSTGRSKFIKMTLEEQS IYLLEV LNLLTNSKTTFDVKPLGITGSRSTIGVKIHNLDEFKI INES ITGLYSNEVTIV SEQ ID NO: 310

MTKLNQPYGIGLDIGSNS IGFAVVDANSHLLRLKGETAIGARLFREGQSAADRRGSRTTRRRLS RTRWRLSFLRDFFAPHITKIDPDFFLRQKYSEI SPKDKDRFKYEKRLFNDRTDAEFYEDYPSMY HLRLHLMTHTHKADPREIFLAIHHILKSRGHFLTPGAAKDFNTDKVDLEDIFPALTEAYAQVYP DLELTFDLAKADDFKAKLLDEQATPSDTQKALVNLLLSSDGEKEIVKKRKQVLTEFAKAITGLK TKFNLALGTEVDEADASNWQFSMGQLDDKWSNIETSMTDQGTEIFEQIQELYRARLLNGIVPAG MSLSQAKVADYGQHKEDLELFKTYLKKLNDHELAKTIRGLYDRYINGDDAKPFLREDFVKALTK EVTAHPNEVSEQLLNRMGQANFMLKQRTKANGAIPIQLQQRELDQI IANQSKYYDWLAAPNPVE AHRWKMPYQLDELLNFHIPYYVGPLITPKQQAESGENVFAWMVRKDPSGNITPYNFDEKVDREA SANTFIQRMKTTDTYLIGEDVLPKQSLLYQKYEVLNELNNVRINNECLGTDQKQRLIREVFERH SSVTIKQVADNLVAHGDFARRPEIRGLADEKRFLSSLSTYHQLKEILHEAIDDPTKLLDIENI I TWSTVFEDHTIFETKLAEIEWLDPKKINELSGIRYRGWGQFSRKLLDGLKLGNGHTVIQELMLS NHNLMQILADETLKETMTELNQDKLKTDDIEDVINDAYTSPSNKKALRQVLRVVEDIKHAANGQ DPSWLFIETADGTGTAGKRTQSRQKQIQTVYANAAQELIDSAVRGELEDKIADKASFTDRLVLY FMQGGRDIYTGAPLNIDQLSHYDIDHILPQSLIKDDSLDNRVLVNATINREKNNVFASTLFAGK MKATWRKWHEAGLI SGRKLRNLMLRPDEIDKFAKGFVARQLVETRQI IKLTEQIAAAQYPNTKI IAVKAGLSHQLREELDFPKNRDVNHYHHAFDAFLAARIGTYLLKRYPKLAPFFTYGEFAKVDVK KFREFNFIGALTHAKK I IAKDTGEIVWDKERDIRELDRIYNFKRMLITHEVYFETADLFKQTI YAAKDSKERGGSKQLIPKKQGYPTQVYGGYTQESGSYNALVRVAEADTTAYQVIKI SAQNASKI ASANLKSREKGKQLLNEIVVKQLAKRRKNWKPSANSFKIVIPRFGMGTLFQNAKYGLFMVNSDT YYRNYQELWLSRENQKLLKKLFS IKYEKTQMNHDALQVYKAI IDQVEKFFKLYDINQFRAKLSD AIERFEKLPINTDGNKIGKTETLRQILIGLQANGTRSNVKNLGIKTDLGLLQVGSGIKLDKDTQ IVYQSPSGLFKRRIPLADL

SEQ ID NO: 311

MTKEYYLGLDVGTNSVGWAVTDSQYNLCKFKKKDMWGIRLFESANTAKDRRLQRGNRRRLERKK QRIDLLQEIFSPEICKIDPTFFIRLNESRLHLEDKSNDFKYPLFIEKDYSDIEYYKEFPTIFHL RKHLIESEEKQDIRLIYLALHNI IKTRGHFLIDGDLQSAKQLRPILDTFLLSLQEEQNLSVSLS ENQKDEYEEILKNRS IAKSEKVKKLKNLFEI SDELEKEEKKAQSAVIENFCKFIVGNKGDVCKF LRVSKEELEIDSFSFSEGKYEDDIVKNLEEKVPEKVYLFEQMKAMYDWNILVDILETEEYI SFA KVKQYEKHKTNLRLLRDI ILKYCTKDEYNRMFNDEKEAGSYTAYVGKLKKNNKKYWIEKKRNPE EFYKSLGKLLDKIEPLKEDLEVLTMMIEECKNHTLLPIQKNKDNGVIPHQVHEVELKKILENAK KYYSFLTETDKDGYSVVQKIES IFRFRIPYYVGPLSTRHQEKGSNVWMVRKPGREDRIYPWNME EI IDFEKSNENFITRMTNKCTYLIGEDVLPKHSLLYSKYMVLNELNNVKVRGKKLPTSLKQKVF EDLFENKSKVTGKNLLEYLQIQDKDIQIDDLSGFDKDFKTSLKSYLDFKKQIFGEEIEKES IQN MIEDI IKWITIYGNDKEMLKRVIRANYSNQLTEEQMKKITGFQYSGWGNFSKMFLKGI SGSDVS TGETFDI ITAMWETDNNLMQILSKKFTFMDNVEDFNSGKVGKIDKITYDSTVKEMFLSPENKRA VWQTIQVAEEIKKVMGCEPKKIFIEMARGGEKVKKRTKSRKAQLLELYAACEEDCRELIKEIED RDERDFNSMKLFLYYTQFGKCMYSGDDIDINELIRGNSKWDRDHIYPQSKIKDDS IDNLVLVNK TYNAKKSNELLSEDIQKKMHSFWLSLLNKKLITKSKYDRLTRKGDFTDEELSGFIARQLVETRQ STKAIADIFKQIYSSEVVYVKSSLVSDFRKKPLNYLKSRRVNDYHHAKDAYLNIVVGNVYNKKF TSNPIQWMKKNRDTNYSLNKVFEHDVVINGEVIWEKCTYHEDTNTYDGGTLDRIRKIVERDNIL YTEYAYCEKGELFNATIQNKNGNSTVSLKKGLDVKKYGGYFSANTSYFSLIEFEDKKGDRARHI IGVPIYIANMLEHSPSAFLEYCEQKGYQNVRILVEKIKKNSLLI INGYPLRIRGENEVDTSFKR AIQLKLDQKNYELVRNIEKFLEKYVEKKGNYPIDENRDHITHEKMNQLYEVLLSKMKKFNKKGM ADPSDRIEKSKPKFIKLEDLIDKINVINKMLNLLRCDNDTKADLSLIELPKNAGSFVVKKNTIG KSKI ILVNQSVTGLYENRREL

SEQ ID NO: 312

MARDYSVGLDIGTSSVGWAAIDNKYHLIRAKSKNLIGVRLFDSAVTAEKRRGYRTTRRRLSRRH WRLRLLNDIFAGPLTDFGDENFLARLKYSWVHPQDQSNQAHFAAGLLFDSKEQDKDFYRKYPTI YHLRLALMNDDQKHDLREVYLAIHHLVKYRGHFLIEGDVKADSAFDVHTFADAIQRYAESNNSD ENLLGKIDEKKLSAALTDKHGSKSQRAETAETAFDILDLQSKKQIQAILKSVVGNQANLMAIFG LDSSAI SKDEQKNYKFSFDDADIDEKIADSEALLSDTEFEFLCDLKAAFDGLTLKMLLGDDKTV SAAMVRRFNEHQKDWEYIKSHIRNAKNAGNGLYEKSKKFDGINAAYLALQSDNEDDRKKAKKIF QDEI SSADIPDDVKADFLKKIDDDQFLPIQRTKNNGTIPHQLHRNELEQI IEKQGIYYPFLKDT YQENSHELNKITALINFRVPYYVGPLVEEEQKIADDGKNIPDPTNHWMVRKSNDTITPWNLSQV VDLDKSGRRFIERLTGTDTYLIGEPTLPKNSLLYQKFDVLQELNNIRVSGRRLDIRAKQDAFEH LFKVQKTVSATNLKDFLVQAGYI SEDTQIEGLADVNGKNFN ALTTYNYLVSVLGREFVENPSN EELLEEITELQTVFEDKKVLRRQLDQLDGLSDHNREKLSRKHYTGWGRI SKKLLTTKIVQNADK IDNQTFDVPRMNQS I IDTLYNTKMNLMEI IN AEDDFGVRAWIDKQNTTDGDEQDVYSLIDELA GPKEIKRGIVQSFRILDDITKAVGYAPKRVYLEFARKTQESHLTNSRKNQLSTLLKNAGLSELV TQVSQYDAAALQNDRLYLYFLQQGKDMYSGEKLNLDNLSNYDIDHI IPQAYTKDNSLDNRVLVS NITNRRKSDSSNYLPALIDKMRPFWSVLSKQGLLSKHKFANLTRTRDFDDMEKERFIARSLVET RQIIKNVASLIDSHFGGETKAVAIRSSLTADMRRYVDIPKNRDINDYHHAFDALLFSTVGQYTE NSGLMKKGQLSDSAGNQYNRYIKEWIHAARLNAQSQRVNPFGFVVGSMRNAAPGKLNPETGEIT PEENADWS IADLDYLHKVMNFRKITVTRRLKDQKGQLYDESRYPSVLHDAKSKAS INFDKHKPV DLYGGFSSAKPAYAALIKFKNKFRLVNVLRQWTYSDKNSEDYILEQIRGKYPKAEMVLSHIPYG QLVKKDGALVTI SSATELHNFEQLWLPLADYKLINTLLKTKEDNLVDILHNRLDLPEMTIESAF YKAFDS ILSFAFNRYALHQNALVKLQAHRDDFNALNYEDKQQTLERILDALHASPASSDLKKIN LSSGFGRLFSPSHFTLADTDEFIFQSVTGLFSTQKTVAQLYQETK

SEQ ID NO: 313

MVYDVGLDIGTGSVGWVALDENGKLARAKGKNLVGVRLFDTAQTAADRRGFRTTRRRLSRRKWR LRLLDELFSAEINEIDSSFFQRLKYSYVHPKDEENKAHYYGGYLFPTEEETKKFHRSYPTIYHL RQELMAQPNKRFDIREIYLAIHHLVKYRGHFLSSQEKITIGSTYNPEDLANAIEVYADEKGLSW ELNNPEQLTEI I SGEAGYGLNKSMKADEALKLFEFDNNQDKVAIKTLLAGLTGNQIDFAKLFGK DISDKDEAKLWKLKLDDEALEEKSQTILSQLTDEEIELFHAVVQAYDGFVLIGLLNGADSVSAA MVQLYDQHREDRKLLKSLAQKAGLKHKRFSEIYEQLALATDEATIKNGI STARELVEESNLSKE VKEDTLRRLDENEFLPKQRTKANSVIPHQLHLAELQKILQNQGQYYPFLLDTFEKEDGQDNKIE ELLRFRIPYYVGPLVTKKDVEHAGGDADNHWVERNEGFEKSRVTPWNFDKVFNRDKAARDFIER LTGNDTYLIGEKTLPQNSLRYQLFTVLNELNNVRVNGKKFDSKTKADLINDLFKARKTVSLSAL KDYLKAQGKGDVTITGLADESKFNSSLSSYNDLKKTFDAEYLENEDNQETLEKI IEIQTVFEDS KIASRELSKLPLDDDQVKKLSQTHYTGWGRLSEKLLDSKI IDERGQKVS ILDKLKSTSQNFMS I INNDKYGVQAWITEQNTGSSKLTFDEKVNELTTSPANKRGIKQSFAVLNDIKKAMKEEPRRVYL EFAREDQTSVRSVPRYNQLKEKYQSKSLSEEAKVLKKTLDGNKNKMSDDRYFLYFQQQGKDMYT GRPINFERLSQDYDIDHI IPQAFTKDDSLDNRVLVSRPENARKSDSFAYTDEVQKQDGSLWTSL LKSGFINRKKYERLTKAGKYLDGQKTGFIARQLVETRQI IKNVASLIEGEYENSKAVAIRSEIT ADMRLLVGIKKHREINSFHHAFDALLITAAGQYMQNRYPDRDSTNVYNEFDRYTNDYLKNLRQL SSRDEVRRLKSFGFVVGTMRKGNEDWSEENTSYLRKVMMFKNILTTKKTEKDRGPLNKETIFSP KSGKKLIPLNSKRSDTALYGGYSNVYSAYMTLVRANGKNLLIKIPI S IANQIEVGNLKINDYIV NNPAIKKFEKILI SKLPLGQLVNEDGNLIYLASNEYRHNAKQLWLSTTDADKIAS I SENSSDEE LLEAYDILTSENVKNRFPFFKKDIDKLSQVRDEFLDSDKRIAVIQTILRGLQIDAAYQAPVKI I SKKVSDWHKLQQSGGIKLSDNSEMIYQSATGIFETRVKI SDLL

SEQ ID NO: 314

IVDYCIGLDLGTGSVGWAVVDMNHRLMKRNGKHLWGSRLFSNAETAANRRASRS IRRRYNKRRE RIRLLRAILQDMVLEKDPTFFIRLEHTSFLDEEDKAKYLGTDYKDNYNLFIDEDFNDYTYYHKY PTIYHLRKALCESTEKADPRLIYLALHHIVKYRGNFLYEGQKFNMDASNIEDKLSDIFTQFTSF NNIPYEDDEKKNLEILEILKKPLSKKAKVDEVMTLIAPEKDYKSAFKELVTGIAGNKMNVTKMI LCEPIKQGDSEIKLKFSDSNYDDQFSEVEKDLGEYVEFVDALHNVYSWVELQTIMGATHTDNAS ISEAMVSRYNKHHDDLKLLKDCIKNNVPNKYFDMFRNDSEKSKGYYNYINRPSKAPVDEFYKYV KKCIEKVDTPEAKQILNDIELENFLLKQNSRTNGSVPYQMQLDEMIKI IDNQAEYYPILKEKRE QLLS ILTFRIPYYFGPLNETSEHAWIKRLEGKENQRILPWNYQDIVDVDATAEGFIKRMRSYCT YFPDEEVLPKNSLIVSKYEVYNELNKIRVDDKLLEVDVKNDIYNELFMKNKTVTEKKLKNWLVN NQCCSKDAEIKGFQKENQFSTSLTPWIDFTNIFGKIDQSNFDLIENI IYDLTVFEDKKIMKRRL KKKYALPDDKVKQILKLKYKDWSRLSKKLLDGIVADNRFGSSVTVLDVLEMSRLNLMEI INDKD LGYAQMIEEATSCPEDGKFTYEEVERLAGSPALKRGIWQSLQIVEEITKVMKCRPKYIYIEFER SEEAKERTESKIKKLENVYKDLDEQTKKEYKSVLEELKGFDNTKKI SSDSLFLYFTQLGKCMYS GKKLDIDSLDKYQIDHIVPQSLVKDDSFDNRVLVVPSENQRKLDDLVVPFDIRDKMYRFWKLLF DHELI SPKKFYSLIKTEYTERDEERFINRQLVETRQITKNVTQI IEDHYSTTKVAAIRANLSHE FRVKNHIYKNRDINDYHHAHDAYIVALIGGFMRDRYPNMHDSKAVYSEYMKMFRKNKNDQKRWK DGFVINSMNYPYEVDGKLIWNPDLINEIKKCFYYKDCYCTTKLDQKSGQLFNLTVLSNDAHADK GVTKAVVPVNKNRSDVHKYGGFSGLQYTIVAIEGQKKKGKKTELVKKI SGVPLHLKAAS INEKI NYIEEKEGLSDVRI IKD IPVNQMIEMDGGEYLLTSPTEYVNARQLVLNEKQCALIADIYNAIY KQDYDNLDDILMIQLYIELTNKMKVLYPAYRGIAEKFESMNENYVVI SKEEKA I IKQMLIVMH RGPQNGNIVYDDFKI SDRIGRLKTKNHNLNNIVFI SQSPTGIYTKKYKL

SEQ ID NO: 315

MKSEKKYYIGLDVGTNSVGWAVTDEFYNILRAKGKDLWGVRLFEKADTAANTRIFRSGRRRNDR KGMRLQILREIFEDEIKKVDKDFYDRLDESKFWAEDKKVSGKYSLFNDKNFSDKQYFEKFPTIF HLRKYLMEEHGKVDIRYYFLAINQMMKRRGHFLIDGQI SHVTDDKPLKEQLILLINDLLKIELE EELMDS IFEILADVNEKRTDKKNNLKELIKGQDFNKQEGNILNS IFES IVTGKAKIKNI I SDED ILEKIKEDNKEDFVLTGDSYEENLQYFEEVLQENITLFNTLKSTYDFLILQS ILKGKSTLSDAQ VERYDEHKKDLEILKKVIKKYDEDGKLFKQVFKEDNGNGYVSYIGYYLNKNKKITAKKKI SNIE FTKYVKGILEKQCDCEDEDVKYLLGKIEQENFLLKQI SS INSVIPHQIHLFELDKILENLAKNY PSFNNKKEEFTKIEKIRKTFTFRIPYYVGPLNDYHKNNGGNAWIFRNKGEKIRPWNFEKIVDLH KSEEEFIKRMLNQCTYLPEETVLPKSS ILYSEYMVLNELNNLRINGKPLDTDVKLKLIEELFKK KTKVTLKS IRDYMVRNNFADKEDFDNSEKNLEIASNMKSYIDFNNILEDKFDVEMVEDLIEKIT IHTGNKKLLKKYIEETYPDLSSSQIQKI INLKYKDWGRLSRKLLDGIKGTKKETEKTDTVINFL RNSSDNLMQI IGSQNYSFNEYIDKLRKKYIPQEI SYEVVENLYVSPSVKKMIWQVIRVTEEITK VMGYDPDKIFIEMAKSEEEKKTTI SRKNKLLDLYKAIKKDERDSQYEKLLTGLNKLDDSDLRSR KLYLYYTQMGRDMYTGEKIDLDKLFDSTHYDKDHI IPQSMKKDDS I INNLVLVNKNANQTTKGN IYPVPSS IRNNPKIYNYWKYLMEKEFI SKEKYNRLIRNTPLTNEELGGFINRQLVETRQSTKAI KELFEKFYQKSKI IPVKASLASDLRKDMNTLKSREVNDLHHAHDAFLNIVAGDVWNREFTSNPI NYVKENREGDKVKYSLSKDFTRPRKSKGKVIWTPEKGRKLIVDTLNKPSVLI SNESHVKKGELF NATIAGKKDYKKGKIYLPLKKDDRLQDVSKYGGYKAINGAFFFLVEHTKSKKRIRS IELFPLHL LSKFYEDKNTVLDYAINVLQLQDPKI I IDKINYRTEI I IDNFSYLISTKSNDGSITVKPNEQMY WRVDEI SNLKKIENKYKKDAILTEEDRKIMESYIDKIYQQFKAGKYKNRRTTDTI IEKYEI IDL DTLDNKQLYQLLVAFI SLSYKTSNNAVDFTVIGLGTECGKPRITNLPDNTYLVYKS ITGIYEKR IRIK

SEQ ID NO: 316

MKLRGIEDDYS IGLDMGTSSVGWAVTDERGTLAHFKRKPTWGSRLFREAQTAAVARMPRGQRRR YVRRRWRLDLLQKLFEQQMEQADPDFFIRLRQSRLLRDDRAEEHADYRWPLFNDCKFTERDYYQ RFPTIYHVRSWLMETDEQADIRLIYLALHNIVKHRGNFLREGQSLSAKSARPDEALNHLRETLR VWSSERGFECS IADNGS ILAMLTHPDLSPSDRRKKIAPLFDVKSDDAAADKKLGIALAGAVIGL KTEFKNIFGDFPCEDSS IYLSNDEAVDAVRSACPDDCAELFDRLCEVYSAYVLQGLLSYAPGQT I SANMVEKYRRYGEDLALLKKLVKIYAPDQYRMFFSGATYPGTGIYDAAQARGYTKYNLGPKKS EYKPSESMQYDDFRKAVEKLFAKTDARADERYRMMMDRFDKQQFLRRLKTSDNGS IYHQLHLEE LKAIVENQGRFYPFLKRDADKLVSLVSFRIPYYVGPLSTRNARTDQHGENRFAWSERKPGMQDE PIFPWNWES I IDRSKSAEKFILRMTGMCTYLQQEPVLPKSSLLYEEFCVLNELNGAHWS IDGDD EHRFDAADREGI IEELFRRKRTVSYGDVAGWMERERNQIGAHVCGGQGEKGFESKLGSYIFFCK DVFKVERLEQSDYPMIERI ILWNTLFEDRKILSQRLKEEYGSRLSAEQIKTICKKRFTGWGRLS EKFLTGITVQVDEDSVS IMDVLREGCPVSGKRGRAMVMMEILRDEELGFQKKVDDFNRAFFAEN AQALGVNELPGSPAVRRSLNQS IRIVDEIAS IAGKAPANIFIEVTRDEDPKKKGRRTKRRYNDL KDALEAFKKEDPELWRELCETAPNDMDERLSLYFMQRGKCLYSGRAIDIHQLSNAGIYEVDHI I PRTYVKDDSLENKALVYREENQRKTDMLLIDPEIRRRMSGYWRMLHEAKLIGDKKFRNLLRSRI DDKALKGFIARQLVETGQMVKLVRSLLEARYPETNI I SVKAS I SHDLRTAAELVKCREANDFHH AHDAFLACRVGLFIQKRHPCVYENPIGLSQVVRNYVRQQADIFKRCRTIPGSSGFIVNSFMTSG FDKETGEIFKDDWDAEAEVEGIRRSLNFRQCFI SRMPFEDHGVFWDATIYSPRAKKTAALPLKQ GLNPSRYGSFSREQFAYFFIYKARNPRKEQTLFEFAQVPVRLSAQIRQDENALERYARELAKDQ GLEFIRIERSKILKNQLIEIDGDRLCITGKEEVRNACELAFAQDEMRVIRMLVSEKPVSRECVI SLFNRILLHGDQASRRLSKQLKLALLSEAFSEASDNVQRNVVLGLIAIFNGSTNMVNLSDIGGS KFAGNVRIKYKKELASPKVNVHLIDQSVTGMFERRTKIGL

SEQ ID NO: 317

MENKQYYIGLDVGTNSVGWAVTDTSYNLLRAKGKDMWGARLFEKANTAAERRTKRTSRRRSERE KARKAMLKELFADEINRVDPSFFIRLEESKFFLDDRSENNRQRYTLFNDATFTDKDYYEKYKTI FHLRSALINSDEKFDVRLVFLAILNLFSHRGHFLNASLKGDGDIQGMDVFYNDLVESCEYFEIE LPRITNIDNFEKILSQKGKSRTKILEELSEELS I SKKDKSKYNLIKLI SGLEASVVELYNIEDI QDENKKIKIGFRESDYEESSLKVKEI IGDEYFDLVERAKSVHDMGLLSNI IGNSKYLCEARVEA YENHHKDLLKIKELLKKYDKKAYNDMFRKMTDKNYSAYVGSVNSNIAKERRSVDKRKIEDLYKY IEDTALKNIPDDNKDKIEILEKIKLGEFLKKQLTASNGVIPNQLQSRELRAILKKAENYLPFLK EKGEKNLTVSEMI IQLFEFQIPYYVGPLDKNPKKDNKANSWAKIKQGGRILPWNFEDKVDVKGS RKEFIEKMVRKCTYI SDEHTLPKQSLLYEKFMVLNEINNIKIDGEKI SVEAKQKIYNDLFVKGK KVSQKDIKKELI SLNIMDKDSVLSGTDTVCNAYLSS IGKFTGVFKEEINKQS IVDMIEDI IFLK TVYGDEKRFVKEEIVEKYGDEIDKDKIKRILGFKFSNWGNLSKSFLELEGADVGTGEVRS HQS LWETNFNLMELLSSRFTYMDELEKRVKKLEKPLSEWTIEDLDDMYLSSPVKRMIWQSMKIVDEI QTVIGYAPKRIFVEMTRSEGEKVRTKSRKDRLKELYNGIKEDSKQWVKELDSKDESYFRSKKMY LYYLQKGRCMYSGEVIELDKLMDDNLYDIDHIYPRSFVKDDSLDNLVLVKKEINNRKQNDPITP QIQASCQGFWKILHDQGFMSNEKYSRLTRKTQEFSDEEKLSFINRQIVETGQATKCMAQILQKS MGEDVDVVFSKARLVSEFRHKFELFKSRLINDFHHANDAYLNIVVGNSYFVKFTRNPANFIKDA RKNPDNPVYKYHMDRFFERDVKSKSEVAWIGQSEGNSGTIVIVKKTMAKNSPLITKKVEEGHGS ITKETIVGVKEIKFGRNKVEKADKTPKKPNLQAYRPIKTSDERLCNILRYGGRTS I S I SGYCLV EYVKKRKTIRSLEAIPVYLGRKDSLSEEKLLNYFRYNLNDGGKDSVSDIRLCLPFI STNSLVKI DGYLYYLGGKNDDRIQLYNAYQLKMKKEEVEYIRKIEKAVSMSKFDEIDREKNPVLTEEKNIEL YNKIQDKFENTVFSKRMSLVKYNKKDLSFGDFLKNKKSKFEEIDLEKQCKVLY I IFNLSNLKE VDLSDIGGSKSTGKCRCKKNITNYKEFKLIQQS ITGLYSCEKDLMTI

SEQ ID NO: 318

MKNLKEYYIGLDIGTASVGWAVTDESYNIPKFNGKKMWGVRLFDDAKTAEERRTQRGSRRRLNR RKERINLLQDLFATEI SKVDPNFFLRLDNSDLYREDKDEKLKSKYTLFNDKDFKDRDYHKKYPT IHHLIMDLIEDEGKKDIRLLYLACHYLLKNRGHFIFEGQKFDTKNSFDKS INDLKIHLRDEY I DLEFNNEDLIEI ITDTTLNKTNKKKELKNIVGDTKFLKAI SAIMIGSSQKLVDLFEDGEFEETT VKSVDFSTTAFDDKYSEYEEALGDTI SLLNILKS IYDSS ILENLLKDADKSKDGNKYI SKAFVK KFNKHGKDLKTLKRI IKKYLPSEYA IFRNKS INDNYVAYTKS ITSNKRTKASKFTKQEDFYK FIKKHLDTIKETKLNSSENEDLKLIDEMLTDIEFKTFIPKLKSSDNGVIPYQLKLMELKKILDN QSKYYDFLNESDEYGTVKDKVES IMEFRIPYYVGPLNPDSKYAWIKRENTKITPWNFKDIVDLD SSREEFIDRLIGRCTYLKEEKVLPKASLIYNEFMVLNELNNLKLNEFLITEEMKKAIFEELFKT KKKVTLKAVSNLLKKEFNLTGDILLSGTDGDFKQGLNSYIDFKNI IGDKVDRDDYRIKIEEI IK LIVLYEDDKTYLKKKIKSAYKNDFTDDEIKKIAALNYKDWGRLSKRFLTGIEGVDKTTGEKGS I IYFMREYNLNLMELMSGHYTFTEEVEKLNPVENRELCYEMVDELYLSPSVKRMLWQSLRVVDEI KRIIGKDPKKIFIEMARAKEAKNSRKESRKNKLLEFYKFGKKAFINEIGEERYNYLLNEINSEE ESKFRWDNLYLYYTQLGRCMYSLEPIDLADLKSN IYDQDHIYPKSKIYDDSLENRVLVKKNLN HEKGNQYPIPEKVLNKNAYGFWKILFDKGLIGQKKYTRLTRRTPFEERELAEFIERQIVETRQA TKETANLLK ICQDSEIVYSKAENASRFRQEFDI IKCRTVNDLHHMHDAYL IVVGNVYNTKFT KNPLNFIKDKDNVRSYNLENMFKYDVVRGSYTAWIADDSEGNVKAATIKKVKRELEGKNYRFTR MSYIGTGGLYDQNLMRKGKGQIPQKENTNKSNIEKYGGYNKASSAYFALIESDGKAGRERTLET IPIMVYNQEKYGNTEAVDKYLKDNLELQDPKILKDKIKINSLIKLDGFLYNIKGKTGDSLSIAG SVQLIVNKEEQKLIKKMDKFLVKKKDNKDIKVTSFD IKEEELIKLYKTLSDKLNNGIYSNKRN NQAKNI SEALDKFKEI S IEEKIDVLNQI ILLFQSYNNGCNLKS IGLSAKTGVVFIPKKLNYKEC KLINQSITGLFENEVDLLNL

SEQ ID NO: 319

MGKMYYLGLDIGTNSVGYAVTDPSYHLLKFKGEPMWGAHVFAAGNQSAERRSFRTSRRRLDRRQ QRVKLVQEIFAPVI SPIDPRFFIRLHESALWRDDVAETDKHIFFNDPTYTDKEYYSDYPTIHHL IVDLMESSEKHDPRLVYLAVAWLVAHRGHFLNEVDKDNIGDVLSFDAFYPEFLAFLSDNGVSPW VCESKALQATLLSRNSVNDKYKALKSLIFGSQKPEDNFDANI SEDGLIQLLAGKKVKVNKLFPQ ESNDASFTLNDKEDAIEEILGTLTPDECEWIAHIRRLFDWAIMKHALKDGRTI SESKVKLYEQH HHDLTQLKYFVKTYLAKEYDDIFRNVDSETTKNYVAYSYHVKEVKGTLPKNKATQEEFCKYVLG KVKNIECSEADKVDFDEMIQRLTDNSFMPKQVSGENRVIPYQLYYYELKTILNKAASYLPFLTQ CGKDAI SNQDKLLS IMTFRIPYFVGPLRKDNSEHAWLERKAGKIYPWNFNDKVDLDKSEEAFIR RMTNTCTYYPGEDVLPLDSLIYEKFMILNEINNIRIDGYPI SVDVKQQVFGLFEKKRRVTVKDI QNLLLSLGALDKHGKLTGIDTTIHSNYNTYHHFKSLMERGVLTRDDVERIVERMTYSDDTKRVR LWLNNNYGTLTADDVKHI SRLRKHDFGRLSKMFLTGLKGVHKETGERAS ILDFMWNTNDNLMQL LSECYTFSDEITKLQEAYYAKAQLSLNDFLDSMYI SNAVKRPIYRTLAVVNDIRKACGTAPKRI FIEMARDGESKKKRSVTRREQIKNLYRS IRKDFQQEVDFLEKILENKSDGQLQSDALYLYFAQL GRDMYTGDPIKLEHIKDQSFYNIDHIYPQSMVKDDSLDNKVLVQSEINGEKSSRYPLDAAIRNK MKPLWDAYYNHGLI SLKKYQRLTRSTPFTDDEKWDFINRQLVETRQSTKALAILLKRKFPDTEI VYSKAGLSSDFRHEFGLVKSRNINDLHHAKDAFLAIVTGNVYHERFNRRWFMVNQPYSVKTKTL FTHS IKNGNFVAWNGEEDLGRIVKMLKQNKNTIHFTRFSFDRKEGLFDIQPLKASTGLVPRKAG LDVVKYGGYDKSTAAYYLLVRFTLEDKKTQHKLMMIPVEGLYKARIDHDKEFLTDYAQTTI SEI LQKDKQKVI IMFPMGTRHIKLNSMI S IDGFYLS IGGKSSKGKSVLCHAMVPLIVPHKIECYIK AMESFARKFKENNKLRIVEKFDKITVEDNLNLYELFLQKLQHNPYNKFFSTQFDVLTNGRSTFT KLSPEEQVQTLLNILS IFKTCRSSGCDLKS INGSAQAARIMI SADLTGLSKKYSDIRLVEQSAS GLFVSKSQNLLEYL

SEQ ID NO: 320

MTKKEQPYNIGLDIGTSSVGWAVTNDNYDLLNIKKKNLWGVRLFEEAQTAKETRLNRSTRRRYR RRKNRINWLNEIFSEELAKTDPSFLIRLQNSWVSKKDPDRKRDKYNLFIDGPYTDKEYYREFPT IFHLRKELILNKDKADIRLIYLALH ILKYRGNFTYEHQKF I SNLNNNLSKELIELNQQLIKY DI SFPDDCDWNHI SDILIGRGNATQKSSNILKDFTLDKETKKLLKEVINLILGNVAHLNTIFKT SLTKDEEKLNFSGKDIESKLDDLDS ILDDDQFTVLDAANRIYSTITLNEILNGESYFSMAKVNQ YENHAIDLCKLRDMWHTTKNEEAVEQSRQAYDDYINKPKYGTKELYTSLKKFLKVALPTNLAKE AEEKI SKGTYLVKPRNSENGVVPYQLNKIEMEKI IDNQSQYYPFLKENKEKLLS ILSFRIPYYV GPLQSAEKNPFAWMERKSNGHARPWNFDEIVDREKSSNKFIRRMTVTDSYLVGEPVLPKNSLIY QRYEVLNELN IRITENLKTNPIGSRLTVETKQRIYNELFKKYKKVTVKKLTKWLIAQGYYKNP ILIGLSQKDEFNSTLTTYLDMKKIFGSSFMEDNKNYDQIEELIEWLTIFEDKQILNEKLHSSKY SYTPDQIKKI SNMRYKGWGRLSKKILMDITTETNTPQLLQLSNYS ILDLMWATNNNFI S IMSND KYDFKNYIENHNLNKNEDQNI SDLVNDIHVSPALKRGITQS IKIVQEIVKFMGHAPKHIFIEVT RETKKSEITTSREKRIKRLQSKLLNKANDFKPQLREYLVPNKKIQEELKKHKNDLSSERIMLYF LQNGKSLYSEESLNINKLSDYQVDHILPRTYIPDDSLENKALVLAKENQRKADDLLLNSNVIDR NLERWTYMLNNNMIGLKKFKNLTRRVITDKDKLGFIHRQLVQTSQMVKGVANILDNMYKNQGTT CIQARANLSTAFRKALSGQDDTYHFKHPELVKNRNVNDFHHAQDAYLASFLGTYRLRRFPTNEM LLMNGEYNKFYGQVKELYSKKKKLPDSRKNGFI I SPLVNGTTQYDRNTGEI IWNVGFRDKILKI FNYHQCNVTRKTEIKTGQFYDQTIYSPKNPKYKKLIAQKKDMDPNIYGGFSGDNKSSITIVKID NNKIKPVAIPIRLINDLKDKKTLQNWLEENVKHKKS IQI IKNNVPIGQI IYSKKVGLLSLNSDR EVANRQQLILPPEHSALLRLLQIPDEDLDQILAFYDKNILVEILQELITKMKKFYPFYKGEREF LIANIENFNQATTSEKVNSLEELITLLHANSTSAHLIFNNIEKKAFGRKTHGLTLNNTDFIYQS VTGLYETRIHIE

SEQ ID NO: 321

MTKFNKNYS IGLDIGVSSVGYAVVTEDYRVPAFKFKVLGNTEKEKIKKNLIGSTTFVSAQPAKG TRVFRVNRRRIDRRNHRITYLRDIFQKEIEKVDKNFYRRLDESFRVLGDKSEDLQIKQPFFGDK ELETAYHKKYPTIYHLRKHLADADKNSPVADIREVYMAI SHILKYRGHFLTLDKINPNNINMQN SWIDFIESCQEVFDLEI SDESKNIADIFKSSENRQEKVKKILPYFQQELLKKDKS IFKQLLQLL FGLKTKFKDCFELEEEPDLNFSKENYDENLENFLGSLEEDFSDVFAKLKVLRDTILLSGMLTYT GATHARFSATMVERYEEHRKDLQRFKFFIKQNLSEQDYLDIFGRKTQNGFDVDKETKGYVGYIT NKMVLTNPQKQKTIQQNFYDYI SGKITGIEGAEYFLNKI SDGTFLRKLRTSDNGAIPNQIHAYE LEKI IERQGKDYPFLLENKDKLLS ILTFKIPYYVGPLAKGSNSRFAWIKRATSSDILDDNDEDT RNGKIRPWNYQKLINMDETRDAFITNLIGNDI ILLNEKVLPKRSLIYEEVMLQNELTRVKYKDK YGKAHFFDSELRQNI INGLFKNNSKRVNAKSLIKYLSDNHKDLNAIEIVSGVEKGKSFNSTLKT YNDLKTIFSEELLDSEIYQKELEEI IKVITVFDDKKSIKNYLTKFFGHLEILDEEKINQLSKLR YSGWGRYSAKLLLDIRDEDTGFNLLQFLRNDEENRNLTKLI SDNTLSFEPKIKDIQSKSTIEDD IFDEIKKLAGSPAIKRGILNS IKIVDELVQI IGYPPHNIVIEMARENMTTEEGQKKAKTRKTKL ESALKNIENSLLENGKVPHSDEQLQSEKLYLYYLQNGKDMYTLDKTGSPAPLYLDQLDQYEVDH I IPYSFLPIDS IDNKVLTHRENNQQKLNNIPDKETVANMKPFWEKLYNAKLI SQTKYQRLTTSE RTPDGVLTESMKAGFIERQLVETRQI IKHVARILDNRFSDTKI ITLKSQLITNFRNTFHIAKIR ELNDYHHAHDAYLAVVVGQTLLKVYPKLAPELIYGHHAHFNRHEENKATLRKHLYSNIMRFFNN PDSKVSKDIWDCNRDLPI IKDVIYNSQINFVKRTMIKKGAFYNQNPVGKFNKQLAANNRYPLKT KALCLDTS IYGGYGPMNSALS I I I IAERFNEKKGKIETVKEFHDIFI IDYEKFNNNPFQFLNDT SENGFLKKNNINRVLGFYRIPKYSLMQKIDGTRMLFESKSNLHKATQFKLTKTQNELFFHMKRL LTKSNLMDLKSKSAIKESQNFILKHKEEFD I SNQLSAFSQKMLGNTTSLKNLIKGYNERKIKE IDIRDETIKYFYDNFIKMFSFVKSGAPKDINDFFDNKCTVARMRPKPDKKLLNATLIHQS ITGL YETRIDLSKLGED

SEQ ID NO: 322

MKQEYFLGLDMGTGSLGWAVTDSTYQVMRKHGKALWGTRLFESASTAEERRMFRTARRRLDRRN WRIQVLQEIFSEEI SKVDPGFFLRMKESKYYPEDKRDAEGNCPELPYALFVDDNYTDKNYHKDY PTIYHLRKMLMETTEIPDIRLVYLVLHHMMKHRGHFLLSGDI SQIKEFKSTFEQLIQNIQDEEL EWHI SLDDAAIQFVEHVLKDRNLTRSTKKSRLIKQLNAKSACEKAILNLLSGGTVKLSDIFNNK ELDESERPKVSFADSGYDDYIGIVEAELAEQYYI IASAKAVYDWSVLVEILGNSVS I SEAKIKV YQKHQADLKTLKKIVRQYMTKEDYKRVFVDTEEKLNNYSAYIGMTKKNGKKVDLKSKQCTQADF YDFLKKNVIKVIDHKEITQEIESEIEKENFLPKQVTKDNGVIPYQVHDYELKKILDNLGTRMPF IKENAEKIQQLFEFRIPYYVGPLNRVDDGKDGKFTWSVRKSDARIYPWNFTEVIDVEASAEKFI RRMTNKCTYLVGEDVLPKDSLVYSKFMVLNELNNLRLNGEKI SVELKQRIYEELFCKYRKVTRK KLERYLVIEGIAKKGVEITGIDGDFKASLTAYHDFKERLTDVQLSQRAKEAIVLNVVLFGDDKK LLKQRLSKMYPNLTTGQLKGICSLSYQGWGRLSKTFLEEITVPAPGTGEVWNIMTALWQTNDNL MQLLSRNYGFTNEVEEFNTLKKETDLSYKTVDELYVSPAVKRQIWQTLKVVKEIQKVMGNAPKR VFVEMAREKQEGKRSDSRKKQLVELYRACKNEERDWITELNAQSDQQLRSDKLFLYYIQKGRCM YSGETIQLDELWDNTKYDIDHIYPQSKTMDDSLNNRVLVKKNYNAIKSDTYPLSLDIQKKMMSF WKMLQQQGFITKEKYVRLVRSDELSADELAGFIERQIVETRQSTKAVATILKEALPDTEIVYVK AGNVSNFRQTYELLKVREMNDLHHAKDAYLNIVVGNAYFVKFTKNAAWFIRNNPGRSYNLKRMF EFDIERSGEIAWKAGNKGS IVTVKKVMQKN ILVTRKAYEVKGGLFDQQIMKKGKGQVPIKGND ERLADIEKYGGYNKAAGTYFMLVKSLDKKGKEIRTIEFVPLYLKNQIEINHESAIQYLAQERGL NSPEILLSKIKIDTLFKVDGFKMWLSGRTGNQLIFKGANQLILSHQEAAILKGVVKYVNRKNEN KDAKLSERDGMTEEKLLQLYDTFLDKLSNTVYS IRLSAQIKTLTEKRAKFIGLSNEDQCIVLNE ILHMFQCQSGSANLKLIGGPGSAGILVMNN ITACKQI SVINQSPTGIYEKEIDLIKL

SEQ ID NO: 323

MKKPYS IGLDIGTNSVGWAVVTDDYKVPAKKMKVLGNTDKSHIEKNLLGALLFDSGNTAEDRRL KRTARRRYTRRRNRILYLQEIFSEEMGKVDDSFFHRLEDSFLVTEDKRGERHPIFGNLEEEVKY HENFPTIYHLRQYLADNPEKVDLRLVYLALAHI IKFRGHFLIEGKFDTRNNDVQRLFQEFLAVY DNTFENSSLQEQNVQVEEILTDKI SKSAKKDRVLKLFPNEKSNGRFAEFLKLIVGNQADFKKHF ELEEKAPLQFSKDTYEEELEVLLAQIGDNYAELFLSAKKLYDS ILLSGILTVTDVGTKAPLSAS MIQRYNEHQMDLAQLKQFIRQKLSDKYNEVFSDVSKDGYAGYIDGKTNQEAFYKYLKGLLNKIE GSGYFLDKIEREDFLRKQRTFDNGS IPHQIHLQEMRAI IRRQAEFYPFLADNQDRIEKLLTFRI PYYVGPLARGKSDFAWLSRKSADKITPWNFDEIVDKESSAEAFINRMTNYDLYLPNQKVLPKHS LLYEKFTVYNELTKVKYKTEQGKTAFFDANMKQEIFDGVFKVYRKVTKDKLMDFLEKEFDEFRI VDLTGLDKENKVFNASYGTYHDLCKILDKDFLDNSKNEKILEDIVLTLTLFEDREMIRKRLENY SDLLTKEQVKKLERRHYTGWGRLSAELIHGIRNKESRKTILDYLIDDGNSNRNFMQLINDDALS FKEEIAKAQVIGETDNLNQVVSDIAGSPAIKKGILQSLKIVDELVKIMGHQPENIVVEMARENQ FTNQGRRNSQQRLKGLTDS IKEFGSQILKEHPVENSQLQNDRLFLYYLQNGRDMYTGEELDIDY LSQYDIDHI IPQAFIKDNS IDNRVLTSSKENRGKSDDVPSKDVVRKMKSYWSKLLSAKLITQRK FDNLTKAERGGLTDDDKAGFIKRQLVETRQITKHVARILDERFNTETDENNKKIRQVKIVTLKS NLVSNFRKEFELYKVREINDYHHAHDAYLNAVIGKALLGVYPQLEPEFVYGDYPHFHGHKENKA TAKKFFYS IMNFFKKDDVRTDKNGEI IWKKDEHI S IKKVLSYPQV IVKKVEEQTGGFSKES ILPKGNSDKLIPRKTKKFYWDTKKYGGFDSPIVAYS ILVIADIEKGKSKKLKTVKALVGVTIME KMTFERDPVAFLERKGYRNVQEE I IKLPKYSLFKLENGRKRLLASARELQKGNEIVLPNHLGT LLYHAKNIHKVDEPKHLDYVDKHKDEFKELLDVVSNFSKKYTLAEGNLEKIKELYAQNNGEDLK ELASSFINLLTFTAIGAPATFKFFDKNIDRKRYTSTTEILNATLIHQSITGLYETRIDLNKLGG D

SEQ ID NO: 324

MDKKYS IGLDIGTNSVGWAVITDEYKVPSKKFKVLGNTDRHS IKKNLIGALLFDSGETAEATRL KRTARRRYTRRKNRICYLQEIFSNEMAKVDDSFFHRLEESFLVEEDKKHERHPIFGNIVDEVAY HEKYPTIYHLRKKLVDSTDKADLRLIYLALAHMIKFRGHFLIEGDLNPDNSDVDKLFIQLVQTY NQLFEENPINASGVDAKAILSARLSKSRRLENLIAQLPGEKKNGLFGNLIALSLGLTPNFKSNF DLAEDAKLQLSKDTYDDDLDNLLAQIGDQYADLFLAAKNLSDAILLSDILRVNTEITKAPLSAS MIKRYDEHHQDLTLLKALVRQQLPEKYKEIFFDQSKNGYAGYIDGGASQEEFYKFIKPILEKMD GTEELLVKLNREDLLRKQRTFDNGS IPHQIHLGELHAILRRQEDFYPFLKDNREKIEKILTFRI PYYVGPLARGNSRFAWMTRKSEETITPWNFEEVVDKGASAQSFIERMTNFDKNLPNEKVLPKHS LLYEYFTVYNELTKVKYVTEGMRKPAFLSGEQKKAIVDLLFKTNRKVTVKQLKEDYFKKIECFD SVEI SGVEDRFNASLGTYHDLLKI IKDKDFLDNEENEDILEDIVLTLTLFEDREMIEERLKTYA HLFDDKVMKQLKRRRYTGWGRLSRKLINGIRDKQSGKTILDFLKSDGFANRNFMQLIHDDSLTF KEDIQKAQVSGQGDSLHEHIANLAGSPAIKKGILQTVKVVDELVKVMGRHKPENIVIEMARENQ TTQKGQKNSRERMKRIEEGIKELGSQILKEHPVENTQLQNEKLYLYYLQNGRDMYVDQELDINR LSDYDVDHIVPQSFLKDDS IDNKVLTRSDKNRGKSDNVPSEEVVKKMKNYWRQLLNAKLITQRK FDNLTKAERGGLSELDKAGFIKRQLVETRQITKHVAQILDSRMNTKYDENDKLIREVKVITLKS KLVSDFRKDFQFYKVREINNYHHAHDAYLNAVVGTALIKKYPKLESEFVYGDYKVYDVRKMIAK SEQEIGKATAKYFFYSNIMNFFKTEITLANGEIRKRPLIETNGETGEIVWDKGRDFATVRKVLS MPQV IVKKTEVQTGGFSKES ILPKRNSDKLIARKKDWDPKKYGGFDSPTVAYSVLVVAKVEKG KSKKLKSVKELLGITIMERSSFEKNPIDFLEAKGYKEVKKDLI IKLPKYSLFELENGRKRMLAS AGELQKGNELALPSKYVNFLYLASHYEKLKGSPEDNEQKQLFVEQHKHYLDEI IEQI SEFSKRV ILADANLDKVLSAYNKHRDKPIREQAE I IHLFTLTNLGAPAAFKYFDTTIDRKRYTSTKEVLD ATLIHQS ITGLYETRIDLSQLGGD

SEQ ID NO: 325

MTKPYS IGLDIGTNSVGWAVTTDNYKVPSKKMKVLGNTSKKYIKKNLLGVLLFDSGITAEGRRL KRTARRRYTRRRNRILYLQEIFSTEMATLDDAFFQRLDDSFLVPDDKRDSKYPIFGNLVEEKAY HDEFPTIYHLRKYLADSTKKADLRLVYLALAHMIKYRGHFLIEGEFNSKNNDIQKNFQDFLDTY NAIFESDLSLENSKQLEEIVKDKI SKLEKKDRILKLFPGEKNSGIFSEFLKLIVGNQADFRKCF NLDEKASLHFSKESYDEDLETLLGYIGDDYSDVFLKAKKLYDAILLSGFLTVTDNETEAPLSSA MIKRYNEHKEDLALLKEYIRNI SLKTYNEVFKDDTKNGYAGYIDGKTNQEDFYVYLKKLLAEFE GADYFLEKIDREDFLRKQRTFDNGS IPYQIHLQEMRAILDKQAKFYPFLAKNKERIEKILTFRI PYYVGPLARGNSDFAWS IRKRNEKITPWNFEDVIDKESSAEAFINRMTSFDLYLPEEKVLPKHS LLYETFNVYNELTKVRFIAESMRDYQFLDSKQKKDIVRLYFKDKRKVTDKDI IEYLHAIYGYDG IELKGIEKQFNSSLSTYHDLLNI INDKEFLDDSSNEAI IEEI IHTLTIFEDREMIKQRLSKFEN IFDKSVLKKLSRRHYTGWGKLSAKLINGIRDEKSGNTILDYLIDDGI SNRNFMQLIHDDALSFK KKIQKAQI IGDEDKGNIKEVVKSLPGSPAIKKGILQS IKIVDELVKVMGGRKPES IVVEMAREN QYTNQGKSNSQQRLKRLEKSLKELGSKILKENIPAKLSKIDNNALQNDRLYLYYLQNGKDMYTG DDLDIDRLSNYDIDHI IPQAFLKDNS IDNKVLVSSASNRGKSDDVPSLEVVKKRKTFWYQLLKS KLI SQRKFDNLTKAERGGLSPEDKAGFIQRQLVETRQITKHVARLLDEKFNNKKDENNRAVRTV KIITLKSTLVSQFRKDFELYKVREINDFHHAHDAYLNAVVASALLKKYPKLEPEFVYGDYPKYN SFRERKSATEKVYFYS IM IFKKS I SLADGRVIERPLIEVNEETGESVWNKESDLATVRRVLS YPQVNVVKKVEEQNHGLDRGKPKGLFNANLSSKPKPNSNENLVGAKEYLDPKKYGGYAGISNSF TVLVKGTIEKGAKKKITNVLEFQGI S ILDRINYRKDKLNFLLEKGYKDIELI IELPKYSLFELS DGSRRMLAS ILSTNNKRGEIHKGNQIFLSQKFVKLLYHAKRI SNTINENHRKYVENHKKEFEEL FYYILEFNENYVGAKKNGKLLNSAFQSWQNHS IDELCSSFIGPTGSERKGLFELTSRGSAADFE FLGVKIPRYRDYTPSSLLKDATLIHQSVTGLYETRIDLAKLGEG

SEQ ID NO: 326

MKKQKFSDYYLGFDIGTNSVGWCVTDLDYNVLRFNKKDMWGSRLFDEAKTAAERRVQRNSRRRL KRRKWRLNLLEEIFSDEIMKIDSNFFRRLKESSLWLEDKNSKEKFTLFNDDNYKDYDFYKQYPT IFHLRDELIKNPEKKDIRLIYLALHS IFKSRGHFLFEGQNLKEIKNFETLYNNLI SFLEDNGIN KS IDKD IEKLEKI ICDSGKGLKDKEKEFKGIFNSDKQLVAIFKLSVGSSVSLNDLFDTDEYKK EEVEKEKI SFREQIYEDDKPIYYS ILGEKIELLDIAKSFYDFMVLNNILSDSNYI SEAKVKLYE EHKKDLKNLKYI IRKYNKENYDKLFKDKNENNYPAYIGLNKEKDKKEVVEKSRLKIDDLIKVIK GYLPKPERIEEKDKTIFNEILNKIELKTILPKQRI SDNGTLPYQIHEVELEKILENQSKYYDFL NYEENGVSTKDKLLKTFKFRIPYYVGPLNSYHKDKGGNSWIVRKEEGKILPWNFEQKVDIEKSA EEFIKRMTNKCTYLNGEDVIPKDSFLYSEYI ILNELNKVQVNDEFLNEENKRKI IDELFKENKK VSEKKFKEYLLVNQIANRTVELKGIKDSFNSNYVSYIKFKDIFGEKLNLDIYKEI SEKS ILWKC LYGDDKKIFEKKIKNEYGDILNKDEIKKINSFKFNTWGRLSEKLLTGIEFINLETGECYSSVME ALRRTNYNLMELLSSKFTLQES IDNENKEMNEVSYRDLIEESYVSPSLKRAILQTLKIYEEIKK ITGRVPKKVFIEMARGGDESMKNKKIPARQEQLKKLYDSCGNDIANFS IDIKEMKNSLSSYDNN SLRQKKLYLYYLQFGKCMYTGREIDLDRLLQNNDTYDIDHIYPRSKVIKDDSFDNLVLVLKNEN AEKSNEYPVKKEIQEKMKSFWRFLKEKNFI SDEKYKRLTGKDDFELRGFMARQLVNVRQTTKEV GKILQQIEPEIKIVYSKAEIASSFREMFDFIKVRELNDTHHAKDAYLNIVAGNVYNTKFTEKPY RYLQEIKENYDVKKIYNYDIKNAWDKENSLEIVKKNMEKNTV ITRFIKEEKGELFNLNPIKKG ETSNEI I S IKPKLYDGKDNKLNEKYGYYTSLKAAYFIYVEHEKKNKKVKTFERITRIDSTLIKN EKNLIKYLVSQKKLLNPKI IKKIYKEQTLI IDSYPYTFTGVDSNKKVELKNKKQLYLEKKYEQI LKNALKFVEDNQGETEENYKFIYLKKRNNNEKNETIDAVKERY IEFNEMYDKFLEKLSSKDYK NYINNKLYTNFLNSKEKFKKLKLWEKSLILREFLKIFNKNTYGKYEIKDSQTKEKLFSFPEDTG RIRLGQSSLGNNKELLEESVTGLFVKKIKL

SEQ ID NO: 327

MKNYTIGLDIGVASVGWVCIDENYKILNYNNRHAFGVHEFESAESAAGRRLKRGMRRRYNRRKK RLQLLQSLFDSYITDSGFFSKTDSQHFWKNNNEFENRSLTEVLSSLRISSRKYPTIYHLRSDLI ESNKKMDLRLVYLALHNLVKYRGHFLQEGNWSEAASAEGMDDQLLELVTRYAELENLSPLDLSE SQWKAAETLLLNRNLTKTDQSKELTAMFGKEYEPFCKLVAGLGVSLHQLFPSSEQALAYKETKT KVQLSNENVEEVMELLLEEESALLEAVQPFYQQVVLYELLKGETYVAKAKVSAFKQYQKDMASL KNLLDKTFGEKVYRSYFI SDKNSQREYQKSHKVEVLCKLDQFNKEAKFAETFYKDLKKLLEDKS KTS IGTTEKDEMLRI IKAIDSNQFLQKQKGIQNAAIPHQNSLYEAEKILRNQQAHYPFITTEWI EKVKQILAFRIPYYIGPLVKDTTQSPFSWVERKGDAPITPWNFDEQIDKAASAEAFI SRMRKTC TYLKGQEVLPKSSLTYERFEVLNELNGIQLRTTGAESDFRHRLSYEMKCWI IDNVFKQYKTVST KRLLQELKKSPYADELYDEHTGEIKEVFGTQKENAFATSLSGYI SMKS ILGAVVDDNPAMTEEL IYWIAVFEDREILHLKIQEKYPS ITDVQRQKLALVKLPGWGRFSRLLIDGLPLDEQGQSVLDHM EQYSSVFMEVLKNKGFGLEKKIQKMNQHQVDGTKKIRYEDIEELAGSPALKRGIWRSVKIVEEL VSIFGEPANIVLEVAREDGEKKRTKSRKDQWEELTKTTLKNDPDLKSFIGEIKSQGDQRFNEQR FWLYVTQQGKCLYTGKALDIQNLSMYEVDHILPQNFVKDDSLDNLALVMPEANQRKNQVGQNKM PLEI IEANQQYAMRTLWERLHELKLI SSGKLGRLKKPSFDEVDKDKFIARQLVETRQI IKHVRD LLDERFSKSDIHLVKAGIVSKFRRFSEIPKIRDYNNKHHAMDALFAAALIQS ILGKYGKNFLAF DLSKKDRQKQWRSVKGSNKEFFLFKNFGNLRLQSPVTGEEVSGVEYMKHVYFELPWQTTKMTQT GDGMFYKES IFSPKVKQAKYVSPKTEKFVHDEVKNHS ICLVEFTFMKKEKEVQETKFIDLKVIE HHQFLKEPESQLAKFLAEKETNSPI IHARI IRTIPKYQKIWIEHFPYYFI STRELHNARQFEI S YELMEKVKQLSERSSVEELKIVFGLLIDQMNDNYPIYTKSS IQDRVQKFVDTQLYDFKSFEIGF EELKKAVAANAQRSDTFGSRI SKKPKPEEVAIGYES ITGLKYRKPRSVVGTKR

SEQ ID NO: 328

MKKEIKDYFLGLDVGTGSVGWAVTDTDYKLLKANRKDLWGMRCFETAETAEVRRLHRGARRRIE RRKKRIKLLQELFSQEIAKTDEGFFQRMKESPFYAEDKTILQENTLFNDKDFADKTYHKAYPTI NHLIKAWIENKVKPDPRLLYLACH I IKKRGHFLFEGDFDSENQFDTS IQALFEYLREDMEVDI DADSQKVKEILKDSSLKNSEKQSRLNKILGLKPSDKQKKAITNLI SGNKINFADLYDNPDLKDA EKNS I SFSKDDFDALSDDLAS ILGDSFELLLKAKAVYNCSVLSKVIGDEQYLSFAKVKIYEKHK TDLTKLKNVIKKHFPKDYKKVFGYNKNEKNNNNYSGYVGVCKTKSKKLI INNSVNQEDFYKFLK TILSAKSEIKEVNDILTEIETGTFLPKQI SKSNAEIPYQLRKMELEKILSNAEKHFSFLKQKDE KGLSHSEKI IMLLTFKIPYYIGPINDNHKKFFPDRCWVVKKEKSPSGKTTPWNFFDHIDKEKTA EAFITSRTNFCTYLVGESVLPKSSLLYSEYTVLNEINNLQI I IDGK ICDIKLKQKIYEDLFKK YKKITQKQISTFIKHEGICNKTDEVI ILGIDKECTSSLKSYIELK IFGKQVDEISTKNMLEEI IRWATIYDEGEGKTILKTKIKAEYGKYCSDEQIKKILNLKFSGWGRLSRKFLETVTSEMPGFSE PVNI ITAMRETQNNLMELLSSEFTFTENIKKINSGFEDAEKQFSYDGLVKPLFLSPSVKKMLWQ TLKLVKEISHITQAPPKKIFIEMAKGAELEPARTKTRLKILQDLYNNCKNDADAFSSEIKDLSG KIENEDNLRLRSDKLYLYYTQLGKCMYCGKPIEIGHVFDTSNYDIDHIYPQSKIKDDS I SNRVL VCSSCNKNKEDKYPLKSEIQSKQRGFWNFLQRNNFI SLEKLNRLTRATPI SDDETAKFIARQLV ETRQATKVAAKVLEKMFPETKIVYSKAETVSMFRNKFDIVKCREINDFHHAHDAYLNIVVGNVY NTKFTNNPWNFIKEKRDNPKIADTYNYYKVFDYDVKRNNITAWEKGKTI ITVKDMLKRNTPIYT RQAACKKGELFNQTIMKKGLGQHPLKKEGPFS I SKYGGYNKVSAAYYTLIEYEEKGNKIRSLE TIPLYLVKDIQKDQDVLKSYLTDLLGKKEFKILVPKIKINSLLKINGFPCHITGKTNDSFLLRP AVQFCCSNNEVLYFKKI IRFSEIRSQREKIGKTI SPYEDLSFRSYIKENLWKKTKNDEIGEKEF YDLLQKKNLEIYDMLLTKHKDTIYKKRPNSATIDILVKGKEKFKSLI IENQFEVILEILKLFSA TRNVSDLQHIGGSKYSGVAKIGNKI SSLDNCILIYQS ITGIFEKRIDLLKV

SEQ ID NO: 329

MEGQMKNNGNNLQQGNYYLGLDVGTSSVGWAVTDTDYNVLKFRGKSMWGARLFDEASTAEERRT HRGNRRRLARRKYRLLLLEQLFEKEIRKIDDNFFVRLHESNLWADDKSKPSKFLLFNDTNFTDK DYLKKYPTIYHLRSDLIHNSTEHDIRLVFLALHHLIKYRGHFIYDNSANGDVKTLDEAVSDFEE YLNENDIEFNIENKKEFINVLSDKHLTKKEKKI SLKKLYGDITDSENINI SVLIEMLSGSS I SL SNLFKDIEFDGKQNLSLDSDIEETLNDVVDILGDNIDLLIHAKEVYDIAVLTSSLGKHKYLCDA KVELFEKNKKDLMILKKYIKKNHPEDYKKIFSSPTEKKNYAAYSQTNSKNVCSQEEFCLFIKPY IRDMVKSENEDEVRIAKEVEDKSFLTKLKGTNNSVVPYQIHERELNQILKNIVAYLPFMNDEQE DI SVVDKIKLIFKFKIPYYVGPLNTKSTRSWVYRSDEKIYPWNFSNVIDLDKTAHEFMNRLIGR CTYTNDPVLPMDSLLYSKYNVLNEINPIKVNGKAIPVEVKQAIYTDLFENSKKKVTRKS IYIYL LKNGYIEKEDIVSGIDIEIKSKLKSHHDFTQIVQENKCTPEEIERI IKGILVYSDDKSMLRRWL KNNIKGLSENDVKYLAKLNYKEWGRLSKTLLTDIYTINPEDGEACS ILDIMWNTNATLMEILSN EKYQFKQNIENYKAENYDEKQNLHEELDDMYI SPAARRS IWQALRIVDEIVDIKKSAPKKIFIE MAREKKSAMKKKRTESRKDTLLELYKSCKSQADGFYDEELFEKLSNESNSRLRRDQLYLYYTQM GRSMYTGKRIDFDKLINDKNTYDIDHIYPRSKIKDDS ITNRVLVEKDINGEKTDIYPI SEDIRQ KMQPFWKILKEKGLINEEKYKRLTRNYELTDEELSSFVARQLVETQQSTKALATLLKKEYPSAK IVYSKAGNVSEFRNRKDKELPKFREINDLHHAKDAYLNIVVGNVYDTKFTEKFFNNIRNENYSL KRVFDFSVPGAWDAKGSTFNTIKKYMAKNNPI IAFAPYEVKGELFDQQIVPKGKGQFPIKQGKD IEKYGGYNKLSSAFLFAVEYKGKKARERSLETVYIKDVELYLQDPIKYCESVLGLKEPQI IKPK ILMGSLFS INNKKLVVTGRSGKQYVCHHIYQLS INDEDSQYLK IAKYLQEEPDG IERQ ILN ITSVN IKLFDVLCTKFNSNTYEI ILNSLKNDVNEGREKFSELDILEQC ILLQLLKAFKCNRE SSNLEKLNNKKQAGVIVIPHLFTKCSVFKVIHQS ITGLFEKEMDLLK

SEQ ID NO: 330

MGRKPYILSLDIGTGSVGYACMDKGFNVLKYHDKDALGVYLFDGALTAQERRQFRTSRRRKNRR IKRLGLLQELLAPLVQNPNFYQFQRQFAWKNDNMDFKNKSLSEVLSFLGYESKKYPTIYHLQEA LLLKDEKFDPELIYMALYHLVKYRGHFLFDHLKIENLTNNDNMHDFVELIETYENLNNIKLNLD YEKTKVIYEILKDNEMTKNDRAKRVKNMEKKLEQFS IMLLGLKFNEGKLFNHADNAEELKGANQ SHTFADNYEENLTPFLTVEQSEFIERANKIYLSLTLQDILKGKKSMAMSKVAAYDKFRNELKQV KDIVYKADSTRTQFKKIFVSSKKSLKQYDATPNDQTFSSLCLFDQYLIRPKKQYSLLIKELKKI IPQDSELYFEAENDTLLKVLNTTDNAS IPMQINLYEAETILRNQQKYHAEITDEMIEKVLSLIQ FRIPYYVGPLVNDHTASKFGWMERKSNES IKPWNFDEVVDRSKSATQFIRRMTNKCSYLINEDV LPKNSLLYQEMEVLNELNATQIRLQTDPKNRKYRMMPQIKLFAVEHIFKKYKTVSHSKFLEIML NSNHRENFMNHGEKLS IFGTQDDKKFASKLSSYQDMTKIFGDIEGKRAQIEEI IQWITIFEDKK ILVQKLKECYPELTSKQINQLKKLNYSGWGRLSEKLLTHAYQGHS I IELLRHSDENFMEILTND VYGFQNFIKEENQVQSNKIQHQDIANLTTSPALKKGIWSTIKLVRELTS IFGEPEKI IMEFATE DQQKGKKQKSRKQLWDD IKKNKLKSVDEYKYI IDVANKLNNEQLQQEKLWLYLSQNGKCMYSG QS IDLDALLSPNATKHYEVDHIFPRSFIKDDS IDNKVLVIKKMNQTKGDQVPLQFIQQPYERIA YWKSLNKAGLI SDSKLHKLMKPEFTAMDKEGFIQRQLVETRQI SVHVRDFLKEEYPNTKVIPMK AKMVSEFRKKFDIPKIRQMNDAHHAIDAYLNGVVYHGAQLAYPNVDLFDFNFKWEKVREKWKAL GEFNTKQKSRELFFFKKLEKMEVSQGERLI SKIKLDMNHFKINYSRKLA IPQQFYNQTAVSPK TAELKYESNKSNEVVYKGLTPYQTYVVAIKSVNKKGKEKMEYQMIDHYVFDFYKFQNGNEKELA LYLAQRENKDEVLDAQIVYSLNKGDLLYINNHPCYFVSRKEVINAKQFELTVEQQLSLYNVMNN KETNVEKLLIEYDFIAEKVINEYHHYLNSKLKEKRVRTFFSESNQTHEDFIKALDELFKVVTAS ATRSDKIGSRKNSMTHRAFLGKGKDVKIAYTS I SGLKTTKPKSLFKLAESRNEL

SEQ ID NO: 331

MAKILGLDLGTNS IGWAVVERENIDFSLIDKGVRIFSEGVKSEKGIESSRAAERTGYRSARKIK YRRKLRKYETLKVLSLNRMCPLS IEEVEEWKKSGFKDYPLNPEFLKWLSTDEESNVNPYFFRDR ASKHKVSLFELGRAFYHIAQRRGFLSNRLDQSAEGILEEHCPKIEAIVEDLI S IDEI STNITDY FFETGILDSNEKNGYAKDLDEGDKKLVSLYKSLLAILKKNESDFENCKSEI IERLNKKDVLGKV KGKIKDI SQAMLDGNYKTLGQYFYSLYSKEKIRNQYTSREEHYLSEFITICKVQGIDQINEEEK INEKKFDGLAKDLYKAIFFQRPLKSQKGLIGKCSFEKSKSRCAI SHPDFEEYRMWTYLNTIKIG TQSDKKLRFLTQDEKLKLVPKFYRKNDFNFDVLAKELIEKGSSFGFYKSSKKNDFFYWFNYKPT DTVAACQVAASLKNAIGEDWKTKSFKYQTINSNKEQVSRTVDYKDLWHLLTVATSDVYLYEFAI DKLGLDEKNAKAFSKTKLKKDFASLSLSAINKILPYLKEGLLYSHAVFVANIENIVDENIWKDE KQRDYIKTQI SEI IENYTLEKSRFEI INGLLKEYKSENEDGKRVYYSKEAEQSFENDLKKKLVL FYKSNEIENKEQQETIFNELLPIFIQQLKDYEFIKIQRLDQKVLIFLKGKNETGQIFCTEEKGT AEEKEKKIKNRLKKLYHPSDIEKFKKKI IKDEFGNEKIVLGSPLTPS IKNPMAMRALHQLRKVL NALILEGQIDEKTI IHIEMARELNDANKRKGIQDYQNDNKKFREDAIKEIKKLYFEDCKKEVEP TEDDILRYQLWMEQNRSEIYEEGKNI S ICDI IGSNPAYDIEHTIPRSRSQDNSQMNKTLCSQRF NREVKKQSMPIELNNHLEILPRIAHWKEEADNLTREIEI I SRS IKAAATKEIKDKKIRRRHYLT LKRDYLQGKYDRFIWEEPKVGFKNSQIPDTGI ITKYAQAYLKSYFKKVESVKGGMVAEFRKIWG IQESFIDENGMKHYKVKDRSKHTHHTIDAITIACMTKEKYDVLAHAWTLEDQQNKKEARS I IEA SKPWKTFKEDLLKIEEEILVSHYTPDNVKKQAKKIVRVRGKKQFVAEVERDVNGKAVPKKAASG KTIYKLDGEGKKLPRLQQGDTIRGSLHQDS IYGAIKNPLNTDEIKYVIRKDLES IKGSDVES IV DEVVKEKIKEAIANKVLLLSSNAQQKNKLVGTVWMNEEKRIAINKVRIYANSVKNPLHIKEHSL LSKSKHVHKQKVYGQNDENYAMAIYELDGKRDFELI IFNLAKLIKQGQGFYPLHKKKEIKGKI VFVPIEKRNKRDVVLKRGQQVVFYDKEVENPKDI SEIVDFKGRIYI IEGLS IQRIVRPSGKVDE YGVIMLRYFKEARKADDIKQDNFKPDGVFKLGENKPTRKMNHQFTAFVEGIDFKVLPSGKFEKI

SEQ ID NO: 332

MEFKKVLGLDIGTNS IGCALLSLPKS IQDYGKGGRLEWLTSRVIPLDADYMKAFIDGKNGLPQV ITPAGKRRQKRGSRRLKHRYKLRRSRLIRVFKTLNWLPEDFPLDNPKRIKETI STEGKFSFRI S DYVPI SDESYREFYREFGYPENEIEQVIEEINFRRKTKGKNKNPMIKLLPEDWVVYYLRKKALI KPTTKEELIRI IYLFNQRRGFKSSRKDLTETAILDYDEFAKRLAEKEKYSAENYETKFVS ITKV KEVVELKTDGRKGKKRFKVILEDSRIEPYEIERKEKPDWEGKEYTFLVTQKLEKGKFKQNKPDL PKEEDWALCTTALDNRMGSKHPGEFFFDELLKAFKEKRGYKIRQYPVNRWRYKKELEFIWTKQC QLNPELNNL INKEILRKLATVLYPSQSKFFGPKIKEFENSDVLHI I SEDI IYYQRDLKSQKSL I SECRYEKRKGIDGEIYGLKCIPKSSPLYQEFRIWQDIH IKVIRKESEVNGKKKI IDETQLY INENIKEKLFELFNSKDSLSEKDILELI SLNI INSGIKI SKKEEETTHRINLFANRKELKGNET KSRYRKVFKKLGFDGEYILNHPSKLNRLWHSDYSNDYADKEKTEKS ILSSLGWKNRNGKWEKSK NYDVFNLPLEVAKAIANLPPLKKEYGSYSALAIRKMLVVMRDGKYWQHPDQIAKDQENTSLMLF DKNLIQLTNNQRKVLNKYLLTLAEVQKRSTLIKQKLNEIEHNPYKLELVSDQDLEKQVLKSFLE KKNESDYLKGLKTYQAGYLIYGKHSEKDVPIVNSPDELGEYIRKKLPNNSLRNPIVEQVIRETI FIVRDVWKSFGI IDEIHIELGRELKNNSEERKKTSESQEKNFQEKERARKLLKELLNSSNFEHY DENGNKIFSSFTVNPNPDSPLDIEKFRIWKNQSGLTDEELNKKLKDEKIPTEIEVKKYILWLTQ KCRSPYTGKI IPLSKLFDSNVYEIEHI IPRSKMKNDSTNNLVICELGVNKAKGDRLAANFI SES NGKCKFGEVEYTLLKYGDYLQYCKDTFKYQKAKYKNLLATEPPEDFIERQINDTRYIGRKLAEL LTPVVKDSKNI IFTIGS ITSELKITWGLNGVWKDILRPRFKRLES I INKKLIFQDEDDPNKYHF DLS INPQLDKEGLKRLDHRHHALDATI IAATTREHVRYLNSLNAADNDEEKREYFLSLCNHKIR DFKLPWENFTSEVKSKLLSCVVSYKESKPILSDPFNKYLKWEYKNGKWQKVFAIQIKNDRWKAV RRSMFKEPIGTVWIKKIKEVSLKEAIKIQAIWEEVKNDPVRKKKEKYIYDDYAQKVIAKIVQEL GLSSSMRKQDDEKLNKFINEAKVSAGVNKNLNTTNKTIYNLEGRFYEKIKVAEYVLYKAKRMPL NKKEYIEKLSLQKMFNDLPNFILEKS ILDNYPEILKELESDNKYI IEPHKKNNPVNRLLLEHIL EYHNNPKEAFSTEGLEKLNKKAINKIGKPIKYITRLDGDINEEEIFRGAVFETDKGSNVYFVMY ENNQTKDREFLKPNPS I SVLKAIEHKNKIDFFAPNRLGFSRI ILSPGDLVYVPTNDQYVLIKDN SSNETI INWDDNEFI SNRIYQVKKFTGNSCYFLKNDIASLILSYSASNGVGEFGSQNI SEYSVD DPPIRIKDVCIKIRVDRLGNVRPL

SEQ ID NO: 333

MKHILGLDLGTNS IGWALIERNIEEKYGKI IGMGSRIVPMGAELSKFEQGQAQTKNADRRTNRG ARRLNKRYKQRRNKLIYILQKLDMLPSQIKLKEDFSDPNKIDKITILPI SKKQEQLTAFDLVSL RVKALTEKVGLEDLGKI IYKYNQLRGYAGGSLEPEKEDIFDEEQSKDKKNKSFIAFSKIVFLGE PQEEIFKNKKLNRRAI IVETEEGNFEGSTFLENIKVGDSLELLINISASKSGDTITIKLPNKTN WRKKMENIENQLKEKSKEMGREFYI SEFLLELLKENRWAKIRNNTILRARYESEFEAIWNEQVK HYPFLENLDKKTLIEIVSFIFPGEKESQKKYRELGLEKGLKYI IKNQVVFYQRELKDQSHLI SD CRYEPNEKAIAKSHPVFQEYKVWEQINKLIVNTKIEAGTNRKGEKKYKYIDRPIPTALKEWIFE ELQNKKEITFSAIFKKLKAEFDLREGIDFLNGMSPKDKLKGNETKLQLQKSLGELWDVLGLDS I NRQIELW ILYNEKGNEYDLTSDRTSKVLEFINKYGN IVDDNAEETAIRI SKIKFARAYSSLS LKAVERILPLVRAGKYFNNDFSQQLQSKILKLLNENVEDPFAKAAQTYLDNNQSVLSEGGVGNS IATILVYDKHTAKEYSHDELYKSYKEINLLKQGDLRNPLVEQI INEALVLIRDIWKNYGIKPNE IRVELARDLKNSAKERATIHKRNKDNQTINNKIKETLVKNKKELSLANIEKVKLWEAQRHLSPY TGQPIPLSDLFDKEKYDVDHI IPI SRYFDDSFTNKVI SEKSVNQEKANRTAMEYFEVGSLKYS I FTKEQFIAHVNEYFSGVKRKNLLATS IPEDPVQRQIKDTQYIAIRVKEELNKIVGNENVKTTTG SITDYLRNHWGLTDKFKLLLKERYEALLESEKFLEAEYDNYKKDFDSRKKEYEEKEVLFEEQEL TREEFIKEYKENYIRYKKNKLI IKGWSKRIDHRHHAIDALIVACTEPAHIKRLNDLNKVLQDWL VEHKSEFMPNFEGSNSELLEEILSLPENERTEIFTQIEKFRAIEMPWKGFPEQVEQKLKEI I I S HKPKDKLLLQYNKAGDRQIKLRGQLHEGTLYGI SQGKEAYRIPLTKFGGSKFATEK IQKIVSP FLSGFIANHLKEYNNKKEEAFSAEGIMDLNNKLAQYRNEKGELKPHTPI STVKIYYKDPSKNKK KKDEEDLSLQKLDREKAFNEKLYVKTGDNYLFAVLEGEIKTKKTSQIKRLYDI I SFFDATNFLK EEFRNAPDKKTFDKDLLFRQYFEERNKAKLLFTLKQGDFVYLPNENEEVILDKESPLYNQYWGD LKERGK IYVVQKFSKKQIYFIKHTIADI IKKDVEFGSQNCYETVEGRS IKENCFKLEIDRLGN IVKVIKR

SEQ ID NO: 334

MHVEIDFPHFSRGDSHLAMNKNEILRGSSVLYRLGLDLGSNSLGWFVTHLEKRGDRHEPVALGP GGVRIFPDGRDPQSGTSNAVDRRMARGARKRRDRFVERRKELIAALIKYNLLPDDARERRALEV LDPYALRKTALTDTLPAHHVGRALFHLNQRRGFQSNRKTDSKQSEDGAIKQAASRLATDKGNET LGVFFADMHLRKSYEDRQTAIRAELVRLGKDHLTGNARKKIWAKVRKRLFGDEVLPRADAPHGV RARATITGTKASYDYYPTRDMLRDEFNAIWAGQSAHHATITDEARTEIEHI IFYQRPLKPAIVG KCTLDPATRPFKEDPEGYRAPWSHPLAQRFRILSEARNLEIRDTGKGSRRLTKEQSDLVVAALL ANREVKFDKLRTLLKLPAEARFNLESDRRAALDGDQTAARLSDKKGFNKAWRGFPPERQIAIVA RLEETEDENELIAWLEKECALDGAAAARVANTTLPDGHCRLGLRAIKKIVPIMQDGLDEDGVAG AGYHIAAKRAGYDHAKLPTGEQLGRLPYYGQWLQDAVVGSGDARDQKEKQYGQFPNPTVHIGLG QLRRVVNDLIDKYGPPTEI S IEFTRALKLSEQQKAERQREQRRNQDKNKARAEELAKFGRPANP RNLLKMRLWEELAHDPLDRKCVYTGEQI S IERLLSDEVDIDHILPVAMTLDDSPANKI ICMRYA NRHKRKQTPSEAFGSSPTLQGHRYNWDDIAARATGLPRNKRWRFDANAREEFDKRGGFLARQLN ETGWLARLAKQYLGAVTDPNQIWVVPGRLTSMLRGKWGLNGLLPSDNYAGVQDKAEEFLASTDD MEFSGVKNRADHRHHAIDGLVTALTDRSLLWKMANAYDEEHEKFVIEPPWPTMRDDLKAALEKM VVSHKPDHGIEGKLHEDSAYGFVKPLDATGLKEEEAGNLVYRKAIESLNENEVDRIRDIQLRTI VRDHVNVEKTKGVALADALRQLQAPSDDYPQFKHGLRHVRILKKEKGDYLVPIANRASGVAYKA YSAGENFCVEVFETAGGKWDGEAVRRFDANKKNAGPKIAHAPQWRDANEGAKLVMRIHKGDLIR LDHEGRARIMVVHRLDAAAGRFKLADHNETGNLDKRHATNNDIDPFRWLMASYNTLKKLAAVPV RVDELGRVWRVMPN

SEQ ID NO: 335

METTLGIDLGTNS IGLALVDQEEHQILYSGVRIFPEGINKDTIGLGEKEESRNATRRAKRQMRR QYFRKKLRKAKLLELLIAYDMCPLKPEDVRRWKNWDKQQKSTVRQFPDTPAFREWLKQNPYELR KQAVTEDVTRPELGRILYQMIQRRGFLSSRKGKEEGKIFTGKDRMVGIDETRKNLQKQTLGAYL YDIAPKNGEKYRFRTERVRARYTLRDMYIREFEI IWQRQAGHLGLAHEQATRKKNIFLEGSATN VRNSKLITHLQAKYGRGHVLIEDTRITVTFQLPLKEVLGGKIEIEEEQLKFKSNESVLFWQRPL RSQKSLLSKCVFEGRNFYDPVHQKWI IAGPTPAPLSHPEFEEFRAYQFINNI IYGKNEHLTAIQ REAVFELMCTESKDFNFEKIPKHLKLFEKFNFDDTTKVPACTTI SQLRKLFPHPVWEEKREEIW HCFYFYDDNTLLFEKLQKDYALQTNDLEKIKKIRLSESYGNVSLKAIRRINPYLKKGYAYSTAV LLGGIRNSFGKRFEYFKEYEPEIEKAVCRILKEKNAEGEVIRKIKDYLVHNRFGFAKNDRAFQK LYHHSQAITTQAQKERLPETGNLRNPIVQQGLNELRRTVNKLLATCREKYGPSFKFDHIHVEMG RELRSSKTEREKQSRQIRENEKKNEAAKVKLAEYGLKAYRDNIQKYLLYKEIEEKGGTVCCPYT GKTLNI SHTLGSDNSVQIEHI IPYS I SLDDSLANKTLCDATFNREKGELTPYDFYQKDPSPEKW GASSWEEIEDRAFRLLPYAKAQRFIRRKPQESNEFI SRQLNDTRYI SKKAVEYLSAICSDVKAF PGQLTAELRHLWGLNNILQSAPDITFPLPVSATENHREYYVITNEQNEVIRLFPKQGETPRTEK GELLLTGEVERKVFRCKGMQEFQTDVSDGKYWRRIKLSSSVTWSPLFAPKPI SADGQIVLKGRI EKGVFVCNQLKQKLKTGLPDGSYWI SLPVI SQTFKEGESVNNSKLTSQQVQLFGRVREGIFRCH NYQCPASGADGNFWCTLDTDTAQPAFTPIKNAPPGVGGGQI ILTGDVDDKGIFHADDDLHYELP ASLPKGKYYGIFTVESCDPTLIPIELSAPKTSKGENLIEGNIWVDEHTGEVRFDPKKNREDQRH HAIDAIVIALSSQSLFQRLSTYNARRENKKRGLDSTEHFPSPWPGFAQDVRQSVVPLLVSYKQN PKTLCKI SKTLYKDGKKIHSCGNAVRGQLHKETVYGQRTAPGATEKSYHIRKDIRELKTSKHIG KVVDITIRQMLLKHLQENYHIDITQEFNIPSNAFFKEGVYRIFLPNKHGEPVPIKKIRMKEELG NAERLKD INQYVNPRNNHHVMIYQDADGNLKEEIVSFWSVIERQNQGQPIYQLPREGR IVS I LQINDTFLIGLKEEEPEVYRNDLSTLSKHLYRVQKLSGMYYTFRHHLASTLNNEREEFRIQSLE AWKRANPVKVQIDEIGRITFLNGPLC

SEQ ID NO: 336

MESSQILSPIGIDLGGKFTGVCLSHLEAFAELPNHANTKYSVILIDHNNFQLSQAQRRATRHRV RNKKRNQFVKRVALQLFQHILSRDLNAKEETALCHYLNNRGYTYVDTDLDEYIKDETTINLLKE LLPSESEHNFIDWFLQKMQSSEFRKILVSKVEEKKDDKELKNAVKNIKNFITGFEKNSVEGHRH RKVYFENIKSDITKDNQLDS IKKKIPSVCLSNLLGHLSNLQWKNLHRYLAKNPKQFDEQTFGNE FLRMLKNFRHLKGSQESLAVRNLIQQLEQSQDYI S ILEKTPPEITIPPYEARTNTGMEKDQSLL LNPEKLNNLYPNWRNLIPGI IDAHPFLEKDLEHTKLRDRKRI I SPSKQDEKRDSYILQRYLDLN KKIDKFKIKKQLSFLGQGKQLPANLIETQKEMETHFNSSLVSVLIQIASAYNKEREDAAQGIWF DNAFSLCELSNINPPRKQKILPLLVGAILSEDFINNKDKWAKFKIFWNTHKIGRTSLKSKCKEI EEARKNSGNAFKIDYEEALNHPEHSNNKALIKI IQTIPDI IQAIQSHLGHNDSQALIYHNPFSL SQLYTILETKRDGFHKNCVAVTCENYWRSQKTEIDPEI SYASRLPADSVRPFDGVLARMMQRLA YEIAMAKWEQIKHIPDNSSLLIPIYLEQNRFEFEESFKKIKGSSSDKTLEQAIEKQNIQWEEKF QRI INASM ICPYKGAS IGGQGEIDHIYPRSLSKKHFGVIFNSEVNLIYCSSQGNREKKEEHYL LEHLSPLYLKHQFGTDNVSDIKNFI SQNVA IKKYI SFHLLTPEQQKAARHALFLDYDDEAFKT ITKFLMSQQKARVNGTQKFLGKQIMEFLSTLADSKQLQLEFS IKQITAEEVHDHRELLSKQEPK LVKSRQQSFPSHAIDATLTMS IGLKEFPQFSQELDNSWFINHLMPDEVHLNPVRSKEKYNKP I SSTPLFKDSLYAERFIPVWVKGETFAIGFSEKDLFEIKPSNKEKLFTLLKTYSTKNPGESLQEL QAKSKAKWLYFPINKTLALEFLHHYFHKEIVTPDDTTVCHFINSLRYYTKKES ITVKILKEPMP VLSVKFESSKKNVLGSFKHTIALPATKDWERLFNHPNFLALKANPAPNPKEFNEFIRKYFLSDN NPNSDIPNNGHNIKPQKHKAVRKVFSLPVIPGNAGTMMRIRRKDNKGQPLYQLQTIDDTPSMGI QINEDRLVKQEVLMDAYKTRNLSTIDGINNSEGQAYATFDNWLTLPVSTFKPEI IKLEMKPHSK TRRYIRITQSLADFIKTIDEALMIKPSDS IDDPLNMPNEIVCKNKLFGNELKPRDGKMKIVSTG KIVTYEFESDSTPQWIQTLYVTQLKKQP

SEQ ID NO: 337

MKKIVGLDLGTNS IGWALINAYINKEHLYGIEACGSRI IPMDAAILGNFDKGNS I SQTADRTSY RGIRRLRERHLLRRERLHRILDLLGFLPKHYSDSLNRYGKFLNDIECKLPWVKDETGSYKFIFQ ESFKEMLANFTEHHPILIANNKKVPYDWTIYYLRKKALTQKI SKEELAWILLNFNQKRGYYQLR GEEEETPNKLVEYYSLKVEKVEDSGERKGKDTWYNVHLENGMIYRRTSNIPLDWEGKTKEFIVT TDLEADGSPKKDKEGNIKRSFRAPKDDDWTLIKKKTEADIDKIKMTVGAYIYDTLLQKPDQKIR GKLVRTIERKYYKNELYQILKTQSEFHEELRDKQLYIACLNELYPNNEPRRNS I STRDFCHLFI EDI IFYQRPLKSKKSLIDNCPYEENRYIDKESGEIKHAS IKCIAKSHPLYQEFRLWQFIVNLRI YRKETDVDVTQELLPTEADYVTLFEWLNEKKEIDQKAFFKYPPFGFKKTTSNYRWNYVEDKPYP CNETHAQI IARLGKAHIPKAFLSKEKEETLWHILYS IEDKQEIEKALHSFANKNNLSEEFIEQF KNFPPFKKEYGSYSAKAIKKLLPLMRMGKYWS IE IDNGTRIRINKI IDGEYDE IRERVRQKA INLTDITHFRALPLWLACYLVYDRHSEVKDIVKWKTPKDIDLYLKSFKQHSLRNPIVEQVITET LRTVRDIWQQVGHIDEIHIELGREMKNPADKRARMSQQMIKNENTNLRIKALLTEFLNPEFGIE NVRPYSPSQQDLLRIYEEGVLNS ILELPEDIGI ILGKFNQTDTLKRPTRSEILRYKLWLEQKYR SPYTGEMIPLSKLFTPAYEIEHI IPQSRYFDDSLSNKVICESEINKLKDRSLGYEFIKNHHGEK VELAFDKPVEVLSVEAYEKLVHESYSHNRSKMKKLLMEDIPDQFIERQLNDSRYI SKVVKSLLS IVREENEQEAI SKNVIPCTGGITDRLKKDWGINDVWNKIVLPRFIRLNELTESTRFTS INTNN TMIPSMPLELQKGFNKKRIDHRHHAMDAI I IACANR IVNYLNNVSASKNTKITRRDLQTLLCH KDKTDNNGNYKWVIDKPWETFTQDTLTALQKITVSFKQNLRVINKTTNHYQHYENGKKIVSNQS KGDSWAIRKSMHKETVHGEVNLRMIKTVSFNEALKKPQAIVEMDLKKKILAMLELGYDTKRIKN YFEENKDTWQDINPSKIKVYYFTKETKDRYFAVRKPIDTSFDKKKIKES ITDTGIQQIMLRHLE TKDNDPTLAFSPDGIDEMNRNILILNKGKKHQPIYKVRVYEKAEKFTVGQKGNKRTKFVEAAKG TNLFFAIYETEEIDKDTKKVIRKRSYSTIPLNVVIERQKQGLSSAPEDENGNLPKYILSPNDLV YVPTQEEINKGEVVMPIDRDRIYKMVDSSGITANFIPASTANLIFALPKATAEIYCNGENCIQN EYGIGSPQSKNQKAITGEMVKEICFPIKVDRLGNI IQVGSCILTN

SEQ ID NO: 338

MSRSLTFSFDIGYAS IGWAVIASASHDDADPSVCGCGTVLFPKDDCQAFKRREYRRLRR IRSR RVRIERIGRLLVQAQI ITPEMKETSGHPAPFYLASEALKGHRTLAPIELWHVLRWYAHNRGYDN NASWSNSLSEDGGNGEDTERVKHAQDLMDKHGTATMAETICRELKLEEGKADAPMEVSTPAYKN LNTAFPRLIVEKEVRRILELSAPLIPGLTAEI IELIAQHHPLTTEQRGVLLQHGIKLARRYRGS LLFGQLIPRFDNRI I SRCPVTWAQVYEAELKKGNSEQSARERAEKLSKVPTANCPEFYEYRMAR ILC IRADGEPLSAEIRRELMNQARQEGKLTKASLEKAI SSRLGKETETNVSNYFTLHPDSEEA LYLNPAVEVLQRSGIGQILSPSVYRIAANRLRRGKSVTPNYLLNLLKSRGESGEALEKKIEKES KKKEADYADTPLKPKYATGRAPYARTVLKKVVEEILDGEDPTRPARGEAHPDGELKAHDGCLYC LLDTDSSVNQHQKERRLDTMTNNHLVRHRMLILDRLLKDLIQDFADGQKDRI SRVCVEVGKELT TFSAMDSKKIQRELTLRQKSHTDAVNRLKRKLPGKALSANLIRKCRIAMDMNWTCPFTGATYGD HELENLELEHIVPHSFRQSNALSSLVLTWPGVNRMKGQRTGYDFVEQEQENPVPDKPNLHICSL NNYRELVEKLDDKKGHEDDRRRKKKRKALLMVRGLSHKHQSQNHEAMKEIGMTEGMMTQSSHLM KLACKS IKTSLPDAHIDMIPGAVTAEVRKAWDVFGVFKELCPEAADPDSGKILKENLRSLTHLH HALDACVLGLIPYI IPAHHNGLLRRVLAMRRIPEKLIPQVRPVANQRHYVLNDDGRMMLRDLSA SLKENIREQLMEQRVIQHVPADMGGALLKETMQRVLSVDGSGEDAMVSLSKKKDGKKEKNQVKA SKLVGVFPEGPSKLKALKAAIEIDGNYGVALDPKPVVIRHIKVFKRIMALKEQNGGKPVRILKK GMLIHLTSSKDPKHAGVWRIES IQDSKGGVKLDLQRAHCAVPKNKTHECNWREVDLI SLLKKYQ MKRYPTSYTGTPR

SEQ ID NO: 339

MTQKVLGLDLGTNS IGSAVRNLDLSDDLQWQLEFFSSDIFRSSVNKESNGREYSLAAQRSAHRR SRGLNEVRRRRLWATLNLLIKHGFCPMSSESLMRWCTYDKRKGLFREYPIDDKDFNAWILLDFN GDGRPDYSSPYQLRRELVTRQFDFEQPIERYKLGRALYHIAQHRGFKSSKGETLSQQETNSKPS STDEIPDVAGAMKASEEKLSKGLSTYMKEHNLLTVGAAFAQLEDEGVRVRNNNDYRAIRSQFQH EIETIFKFQQGLSVESELYERLI SEKKNVGTIFYKRPLRSQRGNVGKCTLERSKPRCAIGHPLF EKFRAWTLINNIKVRMSVDTLDEQLPMKLRLDLYNECFLAFVRTEFKFEDIRKYLEKRLGIHFS YNDKTINYKDSTSVAGCPITARFRKMLGEEWESFRVEGQKERQAHSKNNI SFHRVSYS IEDIWH FCYDAEEPEAVLAFAQETLRLERKKAEELVRIWSAMPQGYAMLSQKAIRNINKILMLGLKYSDA VILAKVPELVDVSDEELLS IAKDYYLVEAQVNYDKRINS IVNGLIAKYKSVSEEYRFADHNYEY LLDESDEKDI IRQIENSLGARRWSLMDANEQTDILQKVRDRYQDFFRSHERKFVESPKLGESFE NYLTKKFPMVEREQWKKLYHPSQITIYRPVSVGKDRSVLRLGNPDIGAIKNPTVLRVLNTLRRR VNQLLDDGVI SPDETRVVVETARELNDANRKWALDTYNRIRHDENEKIKKILEEFYPKRDGI ST DDIDKARYVIDQREVDYFTGSKTYNKDIKKYKFWLEQGGQCMYTGRTINLSNLFDPNAFDIEHT IPESLSFDSSDMNLTLCDAHYNRFIKKNHIPTDMPNYDKAITIDGKEYPAITSQLQRWVERVER LNRNVEYWKGQARRAQNKDRKDQCMREMHLWKMELEYWKKKLERFTVTEVTDGFKNSQLVDTRV ITRHAVLYLKS IFPHVDVQRGDVTAKFRKILGIQSVDEKKDRSLHSHHAIDATTLTI IPVSAKR DRMLELFAKIEEINKMLSFSGSEDRTGLIQELEGLKNKLQMEVKVCRIGHNVSEIGTFINDNII VNHHIKNQALTPVRRRLRKKGYIVGGVDNPRWQTGDALRGEIHKASYYGAITQFAKDDEGKVLM KEGRPQVNPTIKFVIRRELKYKKSAADSGFASWDDLGKAIVDKELFALMKGQFPAETSFKDACE QGIYMIKKGKNGMPDIKLHHIRHVRCEAPQSGLKIKEQTYKSEKEYKRYFYAAVGDLYAMCCYT NGKIREFRIYSLYDVSCHRKSDIEDIPEFITDKKGNRLMLDYKLRTGDMILLYKDNPAELYDLD NVNLSRRLYKINRFESQSNLVLMTHHLSTSKERGRSLGKTVDYQNLPES IRSSVKSLNFLIMGE NRDFVIKNGKI IFNHR

SEQ ID NO: 340

MLVSPI SVDLGGKNTGFFSFTDSLDNSQSGTVIYDESFVLSQVGRRSKRHSKRNNLRNKLVKRL FLLILQEHHGLS IDVLPDEIRGLFNKRGYTYAGFELDEKKKDALESDTLKEFLSEKLQS IDRDS DVEDFLNQIASNAESFKDYKKGFEAVFASATHSPNKKLELKDELKSEYGENAKELLAGLRVTKE ILDEFDKQENQGNLPRAKYFEELGEYIATNEKVKSFFDSNSLKLTDMTKLIG I SNYQLKELRR YFNDKEMEKGDIWIPNKLHKITERFVRSWHPKNDADRQRRAELMKDLKSKEIMELLTTTEPVMT IPPYDDMNNRGAVKCQTLRLNEEYLDKHLPNWRDIAKRLNHGKFNDDLADSTVKGYSEDSTLLH RLLDTSKEIDIYELRGKKPNELLVKTLGQSDANRLYGFAQNYYELIRQKVRAGIWVPVKNKDDS LNLEDNSNMLKRCNHNPPHKKNQIHNLVAGILGVKLDEAKFAEFEKELWSAKVGNKKLSAYCKN IEELRKTHGNTFKIDIEELRKKDPAELSKEEKAKLRLTDDVILNEWSQKIANFFDIDDKHRQRF NNLFSMAQLHTVIDTPRSGFSSTCKRCTAENRFRSETAFYNDETGEFHKKATATCQRLPADTQR PFSGKIERYIDKLGYELAKIKAKELEGMEAKEIKVPI ILEQNAFEYEESLRKSKTGSNDRVINS KKDRDGKKLAKAKENAEDRLKDKDKRIKAFSSGICPYCGDTIGDDGEIDHILPRSHTLKIYGTV FNPEGNLIYVHQKCNQAKADS IYKLSDIKAGVSAQWIEEQVANIKGYKTFSVLSAEQQKAFRYA LFLQNDNEAYKKVVDWLRTDQSARVNGTQKYLAKKIQEKLTKMLPNKHLSFEFILADATEVSEL RRQYARQNPLLAKAEKQAPSSHAIDAVMAFVARYQKVFKDGTPPNADEVAKLAMLDSWNPASNE PLTKGLSTNQKIEKMIKSGDYGQKNMREVFGKS IFGENAIGERYKPIVVQEGGYYIGYPATVKK GYELKNCKVVTSKNDIAKLEKI IKNQDLI SLKENQYIKIFS INKQTI SELSNRYFNMNYKNLVE RDKEIVGLLEFIVENCRYYTKKVDVKFAPKYIHETKYPFYDDWRRFDEAWRYLQENQNKTSSKD RFVIDKSSLNEYYQPDKNEYKLDVDTQPIWDDFCRWYFLDRYKTANDKKS IRIKARKTFSLLAE SGVQGKVFRAKRKIPTGYAYQALPMDNNVIAGDYANILLEANSKTLSLVPKSGI S IEKQLDKKL DVIKKTDVRGLAIDNNSFFNADFDTHGIRLIVENTSVKVGNFPI SAIDKSAKRMIFRALFEKEK GKRKKKTTI SFKESGPVQDYLKVFLKKIVKIQLRTDGS I S IVVRKNAADFTLSFRSEHIQKLL K

SEQ ID NO: 341

MAYRLGLDIGITSVGWAVVALEKDESGLKPVRIQDLGVRIFDKAEDSKTGASLALPRREARSAR RRTRRRRHRLWRVKRLLEQHGILSMEQIEALYAQRTSSPDVYALRVAGLDRCLIAEEIARVLIH IAHRRGFQSNRKSEIKDSDAGKLLKAVQENENLMQSKGYRTVAEMLVSEATKTDAEGKLVHGKK HGYVSNVRNKAGEYRHTVSRQAIVDEVRKIFAAQRALGNDVMSEELEDSYLKILCSQRNFDDGP GGDSPYGHGSVSPDGVRQS IYERMVGSCTFETGEKRAPRSSYSFERFQLLTKVVNLRIYRQQED GGRYPCELTQTERARVIDCAYEQTKITYGKLRKLLDMKDTESFAGLTYGLNRSRNKTEDTVFVE MKFYHEVRKALQRAGVFIQDLS IETLDQIGWILSVWKSDDNRRKKLSTLGLSDNVIEELLPLNG SKFGHLSLKAIRKILPFLEDGYSYDVACELAGYQFQGKTEYVKQRLLPPLGEGEVTNPVVRRAL SQAIKVVNAVIRKHGSPES IHIELARELSKNLDERRKIEKAQKENQKNNEQIKDEIREILGSAH VTGRDIVKYKLFKQQQEFCMYSGEKLDVTRLFEPGYAEVDHI IPYGI SFDDSYDNKVLVKTEQN RQKGNRTPLEYLRDKPEQKAKFIALVES IPLSQKKKNHLLMDKRAIDLEQEGFRERNLSDTRYI TRALMNHIQAWLLFDETASTRSKRVVCVNGAVTAYMRARWGLTKDRDAGDKHHAADAVVVACIG DSLIQRVTKYDKFKRNALADRNRYVQQVSKSEGITQYVDKETGEVFTWESFDERKFLPNEPLEP WPFFRDELLARLSDDPSKNIRAIGLLTYSETEQIDPIFVSRMPTRKVTGAAHKETIRSPRIVKV DDNKGTEIQVVVSKVALTELKLTKDGEIKDYFRPEDDPRLYNTLRERLVQFGGDAKAAFKEPVY KI SKDGSVRTPVRKVKIQEKLTLGVPVHGGRGIAENGGMVRIDVFAKGGKYYFVPIYVADVLKR ELPNRLATAHKPYSEWRVVDDSYQFKFSLYPNDAVMIKPSREVDITYKDRKEPVGCRIMYFVSA NIASAS I SLRTHDNSGELEGLGIQGLEVFEKYVVGPLGDTHPVYKERRMPFRVERKMN

SEQ ID NO: 342

MPVLSPLSPNAAQGRRRWSLALDIGEGS IGWAVAEVDAEGRVLQLTGTGVTLFPSAWSNENGTY VAHGAADRAVRGQQQRHDSRRRRLAGLARLCAPVLERSPEDLKDLTRTPPKADPRAIFFLRADA ARRPLDGPELFRVLHHMAAHRGIRLAELQEVDPPPESDADDAAPAATEDEDGTRRAAADERAFR RLMAEHMHRHGTQPTCGEIMAGRLRETPAGAQPVTRARDGLRVGGGVAVPTRALIEQEFDAIRA IQAPRHPDLPWDSLRRLVLDQAPIAVPPATPCLFLEELRRRGETFQGRTITREAIDRGLTVDPL IQALRIRETVGNLRLHERITEPDGRQRYVPRAMPELGLSHGELTAPERDTLVRALMHDPDGLAA KDGRIPYTRLRKLIGYDNSPVCFAQERDTSGGGITVNPTDPLMARWIDGWVDLPLKARSLYVRD VVARGADSAALARLLAEGAHGVPPVAAAAVPAATAAILESDIMQPGRYSVCPWAAEAILDAWAN APTEGFYDVTRGLFGFAPGEIVLEDLRRARGALLAHLPRTMAAARTPNRAAQQRGPLPAYESVI PSQLITSLRRAHKGRAADWSAADPEERNPFLRTWTGNAATDHILNQVRKTANEVITKYGNRRGW DPLPSRITVELAREAKHGVIRRNEIAKENRENEGRRKKESAALDTFCQDNTVSWQAGGLPKERA ALRLRLAQRQEFFCPYCAERPKLRATDLFSPAETEIDHVIERRMGGDGPDNLVLAHKDCNNAKG KKTPHEHAGDLLDSPALAALWQGWRKENADRLKGKGHKARTPREDKDFMDRVGWRFEEDARAKA EENQERRGRRMLHDTARATRLARLYLAAAVMPEDPAEIGAPPVETPPSPEDPTGYTAIYRTI SR VQPVNGSVTHMLRQRLLQRDKNRDYQTHHAEDACLLLLAGPAVVQAFNTEAAQHGADAPDDRPV DLMPTSDAYHQQRRARALGRVPLATVDAALADIVMPESDRQDPETGRVHWRLTRAGRGLKRRID DLTRNCVILSRPRRPSETGTPGALHNATHYGRREITVDGRTDTVVTQRMNARDLVALLDNAKIV PAARLDAAAPGDTILKEICTEIADRHDRVVDPEGTHARRWI SARLAALVPAHAEAVARDIAELA DLDALADADRTPEQEARRSALRQSPYLGRAI SAKKADGRARAREQEILTRALLDPHWGPRGLRH LIMREARAPSLVRIRANKTDAFGRPVPDAAVWVKTDGNAVSQLWRLTSVVTDDGRRIPLPKPIE KRIEI SNLEYARLNGLDEGAGVTGNNAPPRPLRQDIDRLTPLWRDHGTAPGGYLGTAVGELEDK ARSALRGKAMRQTLTDAGITAEAGWRLDSEGAVCDLEVAKGDTVKKDGKTYKVGVITQGIFGMP VDAAGSAPRTPEDCEKFEEQYGIKPWKAKGIPLA

SEQ ID NO: 343

MNYTEKEKLFMKYILALDIGIASVGWAILDKESETVIEAGSNIFPEASAADNQLRRDMRGAKRN NRRLKTRINDFIKLWENNNLSIPQFKSTEIVGLKVRAITEEITLDELYLILYSYLKHRGISYLE DALDDTVSGSSAYANGLKLNAKELETHYPCEIQQERLNTIGKYRGQSQI INENGEVLDLSNVFT IGAYRKEIQRVFEIQKKYHPELTDEFCDGYMLIFNRKRKYYEGPGNEKSRTDYGRFTTKLDANG NYITEDNIFEKLIGKCSVYPDELRAAAASYTAQEYNVLNDLNNLTINGRKLEENEKHEIVERIK SSNTINMRKI I SDCMGENIDDFAGARIDKSGKEIFHKFEVYNKMRKALLEIGIDI SNYSREELD EIGYIMTINTDKEAMMEAFQKSWIDLSDDVKQCLINMRKTNGALFNKWQSFSLKIMNELIPEMY AQPKEQMTLLTEMGVTKGTQEEFAGLKYIPVDVVSEDIFNPVVRRSVRI SFKILNAVLKKYKAL DTIVIEMPRDRNSEEQKKRINDSQKLNEKEMEYIEKKLAVTYGIKLSPSDFSSQKQLSLKLKLW NEQDGICLYSGKTIDPNDI INNPQLFEIDHI IPRS I SFDDARSNKVLVYRSENQKKGNQTPYYY LTHSHSEWSFEQYKATVMNLSKKKEYAI SRKKIQNLLYSEDITKMDVLKGFINR INDTSYASR LVLNTIQNFFMANEADTKVKVIKGSYTHQMRCNLKLDKNRDESYSHHAVDAMLIGYSELGYEAY HKLQGEFIDFETGEILRKDMWDENMSDEVYADYLYGKKWANIRNEVVKAEKNVKYWHYVMRKSN RGLCNQTIRGTREYDGKQYKINKLDIRTKEGIKVFAKLAFSKKDSDRERLLVYLNDRRTFDDLC KIYEDYSDAANPFVQYEKETGDI IRKYSKKHNGPRIDKLKYKDGEVGACIDI SHKYGFEKGSKK VILESLVPYRMDVYYKEENHSYYLVGVKQSDIKFEKGRNVIDEEAYARILVNEKMIQPGQSRAD LENLGFKFKLSFYKNDI IEYEKDGKIYTERLVSRTMPKQRNYIETKPIDKAKFEKQNLVGLGKT KFIKKYRYDILGNKYSCSEEKFTSFC

SEQ ID NO: 344

MLRLYCANNLVLNNVQNLWKYLLLLIFDKKI IFLFKIKVILIRRYMENNNKEKIVIGFDLGVAS VGWS IVNAETKEVIDLGVRLFSEPEKADYRRAKRTTRRLLRRKKFKREKFHKLILKNAEIFGLQ SRNEILNVYKDQSSKYRNILKLKINALKEEIKPSELVWILRDYLQNRGYFYKNEKLTDEFVSNS FPSKKLHEHYEKYGFFRGSVKLDNKLDNKKDKAKEKDEEEESDAKKESEELIFSNKQWINEIVK VFENQSYLTESFKEEYLKLFNYVRPFNKGPGSKNSRTAYGVFSTDIDPETNKFKDYSNIWDKTI GKCSLFEEEIRAPKNLPSALIFNLQNEICTIKNEFTEFKNWWLNAEQKSEILKFVFTELFNWKD KKYSDKKFNKNLQDKIKKYLLNFALENFNLNEEILKNRDLENDTVLGLKGVKYYEKSNATADAA LEFSSLKPLYVFIKFLKEKKLDLNYLLGLENTEILYFLDS IYLAI SYSSDLKERNEWFKKLLKE LYPKIKNNNLEI IENVEDIFEITDQEKFESFSKTHSLSREAFNHI IPLLLSNNEGKNYESLKHS NEELKKRTEKAELKAQQNQKYLKDNFLKEALVPLSVKTSVLQAIKIFNQI IKNFGKKYEI SQVV IEMARELTKPNLEKLLNNATNSNIKILKEKLDQTEKFDDFTKKKFIDKIENSVVFRNKLFLWFE QDRKDPYTQLDIKINEIEDETEIDHVIPYSKSADDSWFNKLLVKKSTNQLKKNKTVWEYYQNES DPEAKWNKFVAWAKRIYLVQKSDKESKDNSEKNS IFKNKKPNLKFK ITKKLFDPYKDLGFLAR NLNDTRYATKVFRDQLNNYSKHHSKDDENKLFKVVCMNGS ITSFLRKSMWRKNEEQVYRFNFWK KDRDQFFHHAVDAS I IAIFSLLTKTLYNKLRVYESYDVQRREDGVYLINKETGEVKKADKDYWK DQHNFLKIRENAIEIKNVLNNVDFQNQVRYSRKANTKLNTQLFNETLYGVKEFENNFYKLEKVN LFSRKDLRKFILEDLNEESEKNKKNENGSRKRILTEKYIVDEILQILENEEFKDSKSDINALNK YMDSLPSKFSEFFSQDFINKCKKENSLILTFDAIKHNDPKKVIKIKNLKFFREDATLKNKQAVH KDSKNQIKSFYESYKCVGFIWLKNKNDLEES IFVPINSRVIHFGDKDKDIFDFDSYNKEKLLNE INLKRPENKKFNS INEIEFVKFVKPGALLLNFENQQIYYI STLESSSLRAKIKLLNKMDKGKAV SMKKITNPDEYKI IEHVNPLGINLNWTKKLENNN

SEQ ID NO: 345

MLMSKHVLGLDLGVGS IGWCLIALDAQGDPAEILGMGSRVVPLNNATKAIEAFNAGAAFTASQE RTARRTMRRGFARYQLRRYRLRRELEKVGMLPDAALIQLPLLELWELRERAATAGRRLTLPELG RVLCHINQKRGYRHVKSDAAAIVGDEGEKKKDSNSAYLAGIRANDEKLQAEHKTVGQYFAEQLR QNQSESPTGGI SYRIKDQIFSRQCYIDEYDQIMAVQRVHYPDILTDEFIRMLRDEVIFMQRPLK SCKHLVSLCEFEKQERVMRVQQDDGKGGWQLVERRVKFGPKVAPKSSPLFQLCCIYEAVNNIRL TRPNGSPCDITPEERAKIVAHLQSSASLSFAALKKLLKEKALIADQLTSKSGLKGNSTRVALAS ALQPYPQYHHLLDMELETRMMTVQLTDEETGEVTEREVAVVTDSYVRKPLYRLWHILYS IEERE AMRRALITQLGMKEEDLDGGLLDQLYRLDFVKPGYGNKSAKFICKLLPQLQQGLGYSEACAAVG YRHSNSPTSEEITERTLLEKIPLLQRNELRQPLVEKILNQMINLVNALKAEYGIDEVRVELARE LKMSREERERMARNNKDREERNKGVAAKIRECGLYPTKPRIQKYMLWKEAGRQCLYCGRS IEEE QCLREGGMEVEHI IPKSVLYDDSYGNKTCACRRCNKEKGNRTALEYIRAKGREAEYMKRINDLL KEKKI SYSKHQRLRWLKEDIPSDFLERQLRLTQYI SRQAMAILQQGIRRVSASEGGVTARLRSL WGYGKILHTLNLDRYDSMGETERVSREGEATEELHITNWSKRMDHRHHAIDALVVACTRQSYIQ RLNRLSSEFGREDKKKEDQEAQEQQATETGRLSNLERWLTQRPHFSVRTVSDKVAEILI SYRPG QRVVTRGRNIYRKKMADGREVSCVQRGVLVPRGELMEASFYGKILSQGRVRIVKRYPLHDLKGE VVDPHLRELITTYNQELKSREKGAPIPPLCLDKDKKQEVRSVRCYAKTLSLDKAIPMCFDEKGE PTAFVKSASNHHLALYRTPKGKLVES IVTFWDAVDRARYGIPLVITHPREVMEQVLQRGDIPEQ VLSLLPPSDWVFVDSLQQDEMVVIGLSDEELQRALEAQNYRKI SEHLYRVQKMSSSYYVFRYHL ETSVADDKNTSGRIPKFHRVQSLKAYEERNIRKVRVDLLGRISLL

SEQ ID NO: 346

MSDLVLGLDIGIGSVGVGILNKVTGEI IHKNSRIFPAAQAENNLVRRTNRQGRRLARRKKHRRV RLNRLFEESGLITDFTKI S INLNPYQLRVKGLTDELSNEELFIALKNMVKHRGI SYLDDASDDG NSSVGDYAQIVKENSKQLETKTPGQIQLERYQTYGQLRGDFTVEKDGKKHRLINVFPTSAYRSE ALRILQTQQEFNPQITDEFINRYLEILTGKRKYYHGPGNEKSRTDYGRYRTSGETLDNIFGILI GKCTFYPDEFRAAKASYTAQEFNLLNDLNNLTVPTETKKLSKEQKNQI INYVKNEKAMGPAKLF KYIAKLLSCDVADIKGYRIDKSGKAEIHTFEAYRKMKTLETLDIEQMDRETLDKLAYVLTLNTE REGIQEALEHEFADGSFSQKQVDELVQFRKANSS IFGKGWHNFSVKLMMELIPELYETSEEQMT ILTRLGKQKTTSSSNKTKYIDEKLLTEEIYNPVVAKSVRQAIKIVNAAIKEYGDFDNIVIEMAR ETNEDDEKKAIQKIQKANKDEKDAAMLKAANQYNGKAELPHSVFHGHKQLATKIRLWHQQGERC LYTGKTI S IHDLINNSNQFEVDHILPLS ITFDDSLANKVLVYATANQEKGQRTPYQALDSMDDA WSFRELKAFVRESKTLSNKKKEYLLTEEDI SKFDVRKKFIERNLVDTRYASRVVLNALQEHFRA HKIDTKVSVVRGQFTSQLRRHWGIEKTRDTYHHHAVDALI IAASSQLNLWKKQKNTLVSYSEDQ LLDIETGELI SDDEYKESVFKAPYQHFVDTLKSKEFEDS ILFSYQVDSKFNRKI SDATIYATRQ AKVGKDKADETYVLGKIKDIYTQDGYDAFMKIYKKDKSKFLMYRHDPQTFEKVIEPILENYPNK QINEKGKEVPCNPFLKYKEEHGYIRKYSKKGNGPEIKSLKYYDSKLGNHIDITPKDSNNKVVLQ SVSPWRADVYFNKTTGKYEILGLKYADLQFEKGTGTYKI SQEKYNDIKKKEGVDSDSEFKFTLY KNDLLLVKDTETKEQQLFRFLSRTMPKQKHYVELKPYDKQKFEGGEALIKVLGNVANSGQCKKG LGKSNI S IYKVRTDVLGNQHI IKNEGDKPKLDF

SEQ ID NO: 347

MNAEHGKEGLLIMEENFQYRIGLDIGITSVGWAVLQNNSQDEPVRITDLGVRIFDVAENPKNGD ALAAPRRDARTTRRRLRRRRHRLERIKFLLQENGLIEMDSFMERYYKGNLPDVYQLRYEGLDRK LKDEELAQVLIHIAKHRGFRSTRKAETKEKEGGAVLKATTENQKIMQEKGYRTVGEMLYLDEAF HTECLWNEKGYVLTPRNRPDDYKHTILRSMLVEEVHAIFAAQRAHGNQKATEGLEEAYVEIMTS QRSFDMGPGLQPDGKPSPYAMEGFGDRVGKCTFEKDEYRAPKATYTAELFVALQKINHTKLIDE FGTGRFFSEEERKTI IGLLLSSKELKYGTIRKKLNIDPSLKFNSLNYSAKKEGETEEERVLDTE KAKFASMFWTYEYSKCLKDRTEEMPVGEKADLFDRIGEILTAYKNDDSRSSRLKELGLSGEEID GLLDLSPAKYQRVSLKAMRKMQPYLEDGLIYDKACEAAGYDFRALNDGNKKHLLKGEEINAIVN DITNPVVKRSVSQTIKVINAI IQKYGSPQAVNIELAREMSKNFQDRTNLEKEMKKRQQENERAK QQI IELGKQNPTGQDILKYRLWNDQGGYCLYSGKKIPLEELFDGGYDIDHILPYS ITFDDSYRN KVLVTAQENRQKGNRTPYEYFGADEKRWEDYEASVRLLVRDYKKQQKLLKKNFTEEERKEFKER NLNDTKYITRVVYNMIRQNLELEPFNHPEKKKQVWAVNGAVTSYLRKRWGLMQKDRSTDRHHAM DAVVIACCTDGMIHKI SRYMQGRELAYSRNFKFPDEETGEILNRDNFTREQWDEKFGVKVPLPW NSFRDELDIRLLNEDPKNFLLTHADVQRELDYPGWMYGEEESPIEEGRYINYIRPLFVSRMPNH KVTGSAHDATIRSARDYETRGVVITKVPLTDLKLNKDNEIEGYYDKDSDRLLYQALVRQLLLHG NDGKKAFAEDFHKPKADGTEGPVVRKVKIEKKQTSGVMVRGGTGIAANGEMVRIDVFRENGKYY FVPVYTADVVRKVLPNRAATHTKPYSEWRVMDDANFVFSLYSRDLIHVKSKKDIKTNLVNGGLL LQKEIFAYYTGADIATAS IAGFANDSNFKFRGLGIQSLEIFEKCQVDILGNI SVVRHENRQEFH

SEQ ID NO: 348

MRVLGLDAGIASLGWALIEIEESNRGELSQGTI IGAGTWMFDAPEEKTQAGAKLKSEQRRTFRG QRRVVRRRRQRMNEVRRILHSHGLLPSSDRDALKQPGLDPWRIRAEALDRLLGPVELAVALGHI ARHRGFKSNSKGAKTNDPADDTSKMKRAVNETREKLARFGSAAKMLVEDESFVLRQTPTKNGAS EIVRRFRNREGDYSRSLLRDDLAAEMRALFTAQARFQSAIATADLQTAFTKAAFFQRPLQDSEK LVGPCPFEVDEKRAPKRGYSFELFRFLSRLNHVTLRDGKQERTLTRDELALAAADFGAAAKVSF TALRKKLKLPETTVFVGVKADEESKLDVVARSGKAAEGTARLRSVIVDALGELAWGALLCSPEK LDKIAEVI SFRSDIGRI SEGLAQAGCNAPLVDALTAAASDGRFDPFTGAGHI SSKAARNILSGL RQGMTYDKACCAADYDHTASRERGAFDVGGHGREALKRILQEERI SRELVGSPTARKALIES IK QVKAIVERYGVPDRIHVELARDVGKS IEEREEITRGIEKRNRQKDKLRGLFEKEVGRPPQDGAR GKEELLRFELWSEQMGRCLYTDDYI SPSQLVATDDAVQVDHILPWSRFADDSYANKTLCMAKAN QDKKGRTPYEWFKAEKTDTEWDAFIVRVEALADMKGFKKRNYKLRNAEEAAAKFRNRNLNDTRW ACRLLAEALKQLYPKGEKDKDGKERRRVFSRPGALTDRLRRAWGLQWMKKSTKGDRIPDDRHHA LDAIVIAATTESLLQRATREVQEIEDKGLHYDLVKNVTPPWPGFREQAVEAVEKVFVARAERRR ARGKAHDATIRHIAVREGEQRVYERRKVAELKLADLDRVKDAERNARLIEKLRNWIEAGSPKDD PPLSPKGDPIFKVRLVTKSKVNIALDTGNPKRPGTVDRGEMARVDVFRKASKKGKYEYYLVPIY PHDIATMKTPPIRAVQAYKPEDEWPEMDSSYEFCWSLVPMTYLQVI SSKGEIFEGYYRGMNRSV GAIQLSAHSNSSDVVQGIGARTLTEFKKFNVDRFGRKHEVERELRTWRGETWRGKAYI

SEQ ID NO: 349

MGNYYLGLDVGIGS IGWAVINIEKKRIEDFNVRIFKSGEIQEKNRNSRASQQCRRSRGLRRLYR RKSHRKLRLKNYLS I IGLTTSEKIDYYYETADNNVIQLRNKGLSEKLTPEEIAACLIHICNNRG YKDFYEVNVEDIEDPDERNEYKEEHDS IVLI SNLMNEGGYCTPAEMICNCREFDEPNSVYRKFH NSAASKNHYLITRHMLVKEVDLILENQSKYYGILDDKTIAKIKDI IFAQRDFEIGPGKNERFRR FTGYLDS IGKCQFFKDQERGSRFTVIADIYAFVNVLSQYTYTNNRGESVFDTSFANDLINSALK NGSMDKRELKAIAKSYHIDI SDKNSDTSLTKCFKYIKVVKPLFEKYGYDWDKLIENYTDTDNNV LNRIGIVLSQAQTPKRRREKLKALNIGLDDGLINELTKLKLSGTANVSYKYMQGS IEAFCEGDL YGKYQAKFNKEIPDIDENAKPQKLPPFKNEDDCEFFKNPVVFRS INETRKLINAI IDKYGYPAA VNIETADELNKTFEDRAIDTKRNNDNQKENDRIVKEI IECIKCDEVHARHLIEKYKLWEAQEGK CLYSGETITKEDMLRDKDKLFEVDHIVPYSLILDNTINNKALVYAEENQKKGQRTPLMYMNEAQ AADYRVRVNTMFKSKKCSKKKYQYLMLPDLNDQELLGGWRSRNLNDTRYICKYLVNYLRKNLRF DRSYESSDEDDLKIRDHYRVFPVKSRFTSMFRRWWLNEKTWGRYDKAELKKLTYLDHAADAI I I ANCRPEYVVLAGEKLKLNKMYHQAGKRITPEYEQSKKACIDNLYKLFRMDRRTAEKLLSGHGRL TPI IPNLSEEVDKRLWDKNIYEQFWKDDKDKKSCEELYRENVASLYKGDPKFASSLSMPVI SLK PDHKYRGTITGEEAIRVKEIDGKLIKLKRKSISEITAESINSIYTDDKILIDSLKTIFEQADYK DVGDYLKKTNQHFFTTSSGKRVNKVTVIEKVPSRWLRKEIDDNNFSLLNDSSYYCIELYKDSKG DNNLQGIAMSDIVHDRKTKKLYLKPDFNYPDDYYTHVMYIFPGDYLRIKSTSKKSGEQLKFEGY FI SVKNVNENSFRFI SDNKPCAKDKRVS ITKKDIVIKLAVDLMGKVQGENNGKGI SCGEPLSLL KEKN

SEQ ID NO: 350

MLSRQLLGASHLARPVSYSYNVQDNDVHCSYGERCFMRGKRYRIGIDVGLNSVGLAAVEVSDEN SPVRLLNAQSVIHDGGVDPQKNKEAITRKNMSGVARRTRRMRRRKRERLHKLDMLLGKFGYPVI EPESLDKPFEEWHVRAELATRYIEDDELRRES I S IALRHMARHRGWRNPYRQVDSLI SDNPYSK QYGELKEKAKAYNDDATAAEEESTPAQLVVAMLDAGYAEAPRLRWRTGSKKPDAEGYLPVRLMQ EDNANELKQIFRVQRVPADEWKPLFRSVFYAVSPKGSAEQRVGQDPLAPEQARALKASLAFQEY RIANVITNLRIKDASAELRKLTVDEKQS IYDQLVSPSSEDITWSDLCDFLGFKRSQLKGVGSLT EDGEERI SSRPPRLTSVQRIYESDNKIRKPLVAWWKSASDNEHEAMIRLLSNTVDIDKVREDVA YASAIEFIDGLDDDALTKLDSVDLPSGRAAYSVETLQKLTRQMLTTDDDLHEARKTLFNVTDSW RPPADPIGEPLGNPSVDRVLKNVNRYLMNCQQRWGNPVSVNIEHVRSSFSSVAFARKDKREYEK NNEKRS IFRSSLSEQLRADEQMEKVRESDLRRLEAIQRQNGQCLYCGRTITFRTCEMDHIVPRK GVGSTNTRTNFAAVCAECNRMKSNTPFAIWARSEDAQTRGVSLAEAKKRVTMFTFNPKSYAPRE VKAFKQAVIARLQQTEDDAAIDNRS IESVAWMADELHRRIDWYFNAKQYVNSAS IDDAEAETMK TTVSVFQGRVTASARRAAGIEGKIHFIGQQSKTRLDRRHHAVDASVIAMMNTAAAQTLMERESL RESQRLIGLMPGERSWKEYPYEGTSRYESFHLWLDNMDVLLELLNDALDNDRIAVMQSQRYVLG NSIAHDATIHPLEKVPLGSAMSADLIRRASTPALWCALTRLPDYDEKEGLPEDSHREIRVHDTR YSADDEMGFFASQAAQIAVQEGSADIGSAIHHARVYRCWKTNAKGVRKYFYGMIRVFQTDLLRA CHDDLFTVPLPPQS I SMRYGEPRVVQALQSGNAQYLGSLVVGDEIEMDFSSLDVDGQIGEYLQF FSQFSGGNLAWKHWVVDGFFNQTQLRIRPRYLAAEGLAKAFSDDVVPDGVQKIVTKQGWLPPVN TASKTAVRIVRRNAFGEPRLSSAHHMPCSWQWRHE

SEQ ID NO: 351

MYS IGLDLGI SSVGWSVIDERTGNVIDLGVRLFSAKNSEKNLERRTNRGGRRLIRRKTNRLKDA KKILAAVGFYEDKSLKNSCPYQLRVKGLTEPLSRGEIYKVTLHILKKRGI SYLDEVDTEAAKES QDYKEQVRKNAQLLTKYTPGQIQLQRLKENNRVKTGINAQGNYQLNVFKVSAYANELATILKTQ QAFYPNELTDDWIALFVQPGIAEEAGLIYRKRPYYHGPGNEANNSPYGRWSDFQKTGEPAT IF DKLIGKDFQGELRASGLSLSAQQYNLLNDLTNLKIDGEVPLSSEQKEYILTELMTKEFTRFGVN DVVKLLGVKKERLSGWRLDKKGKPEIHTLKGYRNWRKIFAEAGIDLATLPTETIDCLAKVLTLN TEREGIENTLAFELPELSESVKLLVLDRYKELSQS I STQSWHRFSLKTLHLLIPELMNATSEQN TLLEQFQLKSDVRKRYSEYKKLPTKDVLAEIYNPTVNKTVSQAFKVIDALLVKYGKEQIRYITI EMPRDDNEEDEKKRIKELHAKNSQRKNDSQSYFMQKSGWSQEKFQTTIQKNRRFLAKLLYYYEQ DGICAYTGLPI SPELLVSDSTEIDHI IPI S I SLDDS INNKVLVLSKANQVKGQQTPYDAWMDGS FKKINGKFSNWDDYQKWVESRHFSHKKENNLLETRNIFDSEQVEKFLARNLNDTRYASRLVLNT LQSFFTNQETKVRVVNGSFTHTLRKKWGADLDKTRETHHHHAVDATLCAVTSFVKVSRYHYAVK EETGEKVMREIDFETGEIVNEMSYWEFKKSKKYERKTYQVKWPNFREQLKPVNLHPRIKFSHQV DRKANRKLSDATIYSVREKTEVKTLKSGKQKITTDEYTIGKIKDIYTLDGWEAFKKKQDKLLMK DLDEKTYERLLS IAETTPDFQEVEEKNGKVKRVKRSPFAVYCEENDIPAIQKYAKKNNGPLIRS LKYYDGKLNKHI ITKDSQGRPVEKTKNGRKVTLQSLKPYRYDIYQDLETKAYYTVQLYYSDLR FVEGKYGITEKEYMKKVAEQTKGQVVRFCFSLQKNDGLEIEWKDSQRYDVRFYNFQSANS INFK GLEQEMMPAENQFKQKPYNNGAINLNIAKYGKEGKKLRKFNTDILGKKHYLFYEKEPKNIIK

SEQ ID NO: 352

MYFYKNKENKLNKKVVLGLDLGIASVGWCLTDI SQKEDNKFPI ILHGVRLFETVDDSDDKLLNE TRRKKRGQRRRNRRLFTRKRDFIKYLIDNNI IELEFDKNPKILVRNFIEKYINPFSKNLELKYK SVTNLPIGFHNLRKAAINEKYKLDKSELIVLLYFYLSLRGAFFDNPEDTKSKEMNKNEIEIFDK NES IKNAEFPIDKI IEFYKI SGKIRSTINLKFGHQDYLKEIKQVFEKQNIDFMNYEKFAMEEKS FFSRIRNYSEGPGNEKSFSKYGLYANENGNPELI INEKGQKIYTKIFKTLWESKIGKCSYDKKL YRAPKNSFSAKVFDITNKLTDWKHKNEYI SERLKRKILLSRFLNKDSKSAVEKILKEENIKFEN LSEIAYNKDDNKINLPI INAYHSLTTIFKKHLINFENYLI SNENDLSKLMSFYKQQSEKLFVPN EKGSYEINQNNNVLHIFDAISNILNKFSTIQDRIRILEGYFEFSNLKKDVKSSEIYSEIAKLRE FSGTSSLSFGAYYKFIPNLISEGSKNYSTISYEEKALQNQKNNFSHSNLFEKTWVEDLIASPTV KRSLRQTMNLLKEIFKYSEKNNLEIEKIVVEVTRSSNNKHERKKIEGINKYRKEKYEELKKVYD LPNENTTLLKKLWLLRQQQGYDAYSLRKIEANDVINKPWNYDIDHIVPRS I SFDDSFSNLVIVN KLDNAKKSNDLSAKQFIEKIYGIEKLKEAKENWGNWYLRNANGKAFNDKGKFIKLYTIDNLDEF DNSDFINRNLSDTSYITNALVNHLTFSNSKYKYSVVSVNGKQTSNLRNQIAFVGIKNNKETERE WKRPEGFKSINSNDFLIREEGKNDVKDDVLIKDRSFNGHHAEDAYFITI ISQYFRSFKRIERLN VNYRKETRELDDLEKNNIKFKEKASFDNFLLINALDELNEKLNQMRFSRMVITKKNTQLFNETL YSGKYDKGKNTIKKVEKLNLLDNRTDKIKKIEEFFDEDKLKENELTKLHIFNHDKNLYETLKII WNEVKIEIKNKNLNEKNYFKYFVNKKLQEGKI SFNEWVPILDNDFKI IRKIRYIKFSSEEKETD EI IFSQSNFLKIDQRQNFSFHNTLYWVQIWVYKNQKDQYCFI S IDARNSKFEKDEIKINYEKLK TQKEKLQI INEEPILKINKGDLFENEEKELFYIVGRDEKPQKLEIKYILGKKIKDQKQIQKPVK KYFPNWKKVNLTYMGEIFKK

SEQ ID NO: 353

MDNKNYRIGIDVGLNS IGFCAVEVDQHDTPLGFLNLSVYRHDAGIDPNGKKTNTTRLAMSGVAR RTRRLFRKRKRRLAALDRFIEAQGWTLPDHADYKDPYTPWLVRAELAQTPIRDENDLHEKLAIA VRHIARHRGWRSPWVPVRSLHVEQPPSDQYLALKERVEAKTLLQMPEGATPAEMVVALDLSVDV NLRPKNREKTDTRPENKKPGFLGGKLMQSDNANELRKIAKIQGLDDALLRELIELVFAADSPKG ASGELVGYDVLPGQHGKRRAEKAHPAFQRYRIAS IVSNLRIRHLGSGADERLDVETQKRVFEYL LNAKPTADITWSDVAEEIGVERNLLMGTATQTADGERASAKPPVDVTNVAFATCKIKPLKEWWL NADYEARCVMVSALSHAEKLTEGTAAEVEVAEFLQNLSDEDNEKLDSFSLPIGRAAYSVDSLER LTKRMIENGEDLFEARVNEFGVSEDWRPPAEPIGARVGNPAVDRVLKAVNRYLMAAEAEWGAPL SV IEHVREGFI SKRQAVEIDRENQKRYQRNQAVRSQIADHINATSGVRGSDVTRYLAIQRQNG ECLYCGTAITFVNSEMDHIVPRAGLGSTNTRDNLVATCERCNKSKSNKPFAVWAAECGIPGVSV AEALKRVDFWIADGFASSKEHRELQKGVKDRLKRKVSDPEIDNRSMESVAWMARELAHRVQYYF DEKHTGTKVRVFRGSLTSAARKASGFESRVNFIGGNGKTRLDRRHHAMDAATVAMLRNSVAKTL VLRGNIRASERAIGAAETWKSFRGENVADRQIFESWSENMRVLVEKFNLALYNDEVS IFSSLRL QLGNGKAHDDTITKLQMHKVGDAWSLTEIDRASTPALWCALTRQPDFTWKDGLPANEDRTIIVN GTHYGPLDKVGIFGKAAASLLVRGGSVDIGSAIHHARIYRIAGKKPTYGMVRVFAPDLLRYRNE DLFNVELPPQSVSMRYAEPKVREAIREGKAEYLGWLVVGDELLLDLSSETSGQIAELQQDFPGT THWTVAGFFSPSRLRLRPVYLAQEGLGEDVSEGSKS I IAGQGWRPAVNKVFGSAMPEVIRRDGL GRKRRFSYSGLPVSWQG

SEQ ID NO: 354

MRLGLDIGTSS IGWWLYETDGAGSDARITGVVDGGVRIFSDGRDPKSGASLAVDRRAARAMRRR RDRYLRRRATLMKVLAETGLMPADPAEAKALEALDPFALRAAGLDEPLPLPHLGRALFHLNQRR GFKSNRKTDRGDNESGKIKDATARLDMEMMANGARTYGEFLHKRRQKATDPRHVPSVRTRLSIA NRGGPDGKEEAGYDFYPDRRHLEEEFHKLWAAQGAHHPELTETLRDLLFEKIFFQRPLKEPEVG LCLFSGHHGVPPKDPRLPKAHPLTQRRVLYETVNQLRVTADGREARPLTREERDQVIHALDNKK PTKSLSSMVLKLPALAKVLKLRDGERFTLETGVRDAIACDPLRASPAHPDRFGPRWS ILDADAQ WEVI SRIRRVQSDAEHAALVDWLTEAHGLDRAHAEATAHAPLPDGYGRLGLTATTRILYQLTAD VVTYADAVKACGWHHSDGRTGECFDRLPYYGEVLERHVIPGSYHPDDDDITRFGRITNPTVHIG LNQLRRLVNRI IETHGKPHQIVVELARDLKKSEEQKRADIKRIRDTTEAAKKRSEKLEELEIED NGRNRMLLRLWEDLNPDDAMRRFCPYTGTRI SAAMIFDGSCDVDHILPYSRTLDDSFPNRTLCL REANRQKRNQTPWQAWGDTPHWHAIAANLKNLPENKRWRFAPDAMTRFEGENGFLDRALKDTQY LARI SRSYLDTLFTKGGHVWVVPGRFTEMLRRHWGLNSLLSDAGRGAVKAKNRTDHRHHAIDAA VIAATDPGLLNRI SRAAGQGEAAGQSAELIARDTPPPWEGFRDDLRVRLDRI IVSHRADHGRID HAARKQGRDSTAGQLHQETAYS IVDDIHVASRTDLLSLKPAQLLDEPGRSGQVRDPQLRKALRV ATGGKTGKDFENALRYFASKPGPYQAIRRVRI IKPLQAQARVPVPAQDPIKAYQGGSNHLFEIW RLPDGEIEAQVITSFEAHTLEGEKRPHPAAKRLLRVHKGDMVALERDGRRVVGHVQKMDIANGL FIVPHNEANADTRNNDKSDPFKWIQIGARPAIASGIRRVSVDEIGRLRDGGTRPI

SEQ ID NO: 355

MLHCIAVIRVPPSEEPGFFETHADSCALCHHGCMTYAANDKAIRYRVGIDVGLRS IGFCAVEVD DEDHPIRILNSVVHVHDAGTGGPGETESLRKRSGVAARARRRGRAEKQRLKKLDVLLEELGWGV SSNELLDSHAPWHIRKRLVSEYIEDETERRQCLSVAMAHIARHRGWRNSFSKVDTLLLEQAPSD RMQGLKERVEDRTGLQFSEEVTQGELVATLLEHDGDVTIRGFVRKGGKATKVHGVLEGKYMQSD LVAELRQICRTQRVSETTFEKLVLS IFHSKEPAPSAARQRERVGLDELQLALDPAAKQPRAERA HPAFQKFKVVATLANMRIREQSAGERSLTSEELNRVARYLLNHTESESPTWDDVARKLEVPRHR LRGSSRASLETGGGLTYPPVDDTTVRVMSAEVDWLADWWDCANDESRGHMIDAI SNGCGSEPDD VEDEEVNELI SSATAEDMLKLELLAKKLPSGRVAYSLKTLREVTAAILETGDDLSQAITRLYGV DPGWVPTPAPIEAPVGNPSVDRVLKQVARWLKFASKRWGVPQTVNIEHTREGLKSASLLEEERE RWERFEARREIRQKEMYKRLGI SGPFRRSDQVRYEILDLQDCACLYCGNEINFQTFEVDHI IPR VDASSDSRRTNLAAVCHSCNSAKGGLAFGQWVKRGDCPSGVSLENAIKRVRSWSKDRLGLTEKA MGKRKSEVI SRLKTEMPYEEFDGRSMESVAWMAIELKKRIEGYFNSDRPEGCAAVQVNAYSGRL TACARRAAHVDKRVRLIRLKGDDGHHKNRFDRRNHAMDALVIALMTPAIARTIAVREDRREAQQ LTRAFESWKNFLGSEERMQDRWESWIGDVEYACDRLNELIDADKIPVTENLRLRNSGKLHADQP ESLKKARRGSKRPRPQRYVLGDALPADVINRVTDPGLWTALVRAPGFDSQLGLPADLNRGLKLR GKRI SADFPIDYFPTDSPALAVQGGYVGLEFHHARLYRI IGPKEKVKYALLRVCAIDLCGIDCD DLFEVELKPSS I SMRTADAKLKEAMGNGSAKQIGWLVLGDEIQIDPTKFPKQS IGKFLKECGPV SSWRVSALDTPSKITLKPRLLSNEPLLKTSRVGGHESDLVVAECVEKIMKKTGWVVEINALCQS GLIRVIRRNALGEVRTSPKSGLPI SLNLR

SEQ ID NO: 356

MRYRVGLDLGTASVGAAVFSMDEQGNPMELIWHYERLFSEPLVPDMGQLKPKKAARRLARQQRR QIDRRASRLRRIAIVSRRLGIAPGRNDSGVHGNDVPTLRAMAVNERIELGQLRAVLLRMGKKRG YGGTFKAVRKVGEAGEVASGASRLEEEMVALASVQNKDSVTVGEYLAARVEHGLPSKLKVAANN EYYAPEYALFRQYLGLPAIKGRPDCLPNMYALRHQIEHEFERIWATQSQFHDVMKDHGVKEEIR NAIFFQRPLKSPADKVGRCSLQTNLPRAPRAQIAAQNFRIEKQMADLRWGMGRRAEMLNDHQKA VIRELLNQQKELSFRKIYKELERAGCPGPEGKGLNMDRAALGGRDDLSGNTTLAAWRKLGLEDR WQELDEVTQIQVINFLADLGSPEQLDTDDWSCRFMGKNGRPRNFSDEFVAFMNELRMTDGFDRL SKMGFEGGRSSYS IKALKALTEWMIAPHWRETPETHRVDEEAAIRECYPESLATPAQGGRQSKL EPPPLTGNEVVDVALRQVRHTINMMIDDLGSVPAQIVVEMAREMKGGVTRRNDIEKQNKRFASE RKKAAQS IEENGKTPTPARILRYQLWIEQGHQCPYCESNI SLEQALSGAYTNFEHILPRTLTQI GRKRSELVLAHRECNDEKGNRTPYQAFGHDDRRWRIVEQRANALPKKSSRKTRLLLLKDFEGEA LTDES IDEFADRQLHESSWLAKVTTQWLSSLGSDVYVSRGSLTAELRRRWGLDTVIPQVRFESG MPVVDEEGAEITPEEFEKFRLQWEGHRVTREMRTDRRPDKRIDHRHHLVDAIVTALTSRSLYQQ YAKAWKVADEKQRHGRVDVKVELPMPILTIRDIALEAVRSVRI SHKPDRYPDGRFFEATAYGIA QRLDERSGEKVDWLVSRKSLTDLAPEKKS IDVDKVRANI SRIVGEAIRLHI SNIFEKRVSKGMT PQQALREPIEFQGNILRKVRCFYSKADDCVRIEHSSRRGHHYKMLLNDGFAYMEVPCKEGILYG VPNLVRPSEAVGIKRAPESGDFIRFYKGDTVKNIKTGRVYTIKQILGDGGGKLILTPVTETKPA DLLSAKWGRLKVGGRNIHLLRLCAE

SEQ ID NO: 357 MIGEHVRGGCLFDDHWTPNWGAFRLPNTVRTFTKAENPKDGSSLAEPRRQARGLRRRLRRKTQR LEDLRRLLAKEGVLSLSDLETLFRETPAKDPYQLRAEGLDRPLSFPEWVRVLYHITKHRGFQSN RRNPVEDGQERSRQEEEGKLLSGVGENERLLREGGYRTAGEMLARDPKFQDHRRNRAGDYSHTL SRSLLLEEARRLFQSQRTLGNPHASSNLEEAFLHLVAFQNPFASGEDIRNKAGHCSLEPDQIRA PRRSASAETFMLLQKTGNLRLIHRRTGEERPLTDKEREQIHLLAWKQEKVTHKTLRRHLEIPEE WLFTGLPYHRSGDKAEEKLFVHLAGIHEIRKALDKGPDPAVWDTLRSRRDLLDS IADTLTFYKN EDEILPRLESLGLSPENARALAPLSFSGTAHLSLSALGKLLPHLEEGKSYTQARADAGYAAPPP DRHPKLPPLEEADWRNPVVFRALTQTRKVVNALVRRYGPPWCIHLETARELSQPAKVRRRIETE QQANEKKKQQAEREFLDIVGTAPGPGDLLKMRLWREQGGFCPYCEEYLNPTRLAEPGYAEMDHI LPYSRSLDNGWHNRVLVHGKDNRDKGNRTPFEAFGGDTARWDRLVAWVQASHLSAPKKRNLLRE DFGEEAERELKDRNLTDTRFITKTAATLLRDRLTFHPEAPKDPVMTLNGRLTAFLRKQWGLHKN RKNGDLHHALDAAVLAVASRSFVYRLSSHNAAWGELPRGREAENGFSLPYPAFRSEVLARLCPT REEILLRLDQGGVGYDEAFRNGLRPVFVSRAPSRRLRGKAHMETLRSPKWKDHPEGPRTASRIP LKDLNLEKLERMVGKDRDRKLYEALRERLAAFGGNGKKAFVAPFRKPCRSGEGPLVRSLRIFDS GYSGVELRDGGEVYAVADHESMVRVDVYAKKNRFYLVPVYVADVARGIVKNRAIVAHKSEEEWD LVDGSFDFRFSLFPGDLVEIEKKDGAYLGYYKSCHRGDGRLLLDRHDRMPRESDCGTFYVSTRK DVLSMSKYQVDPLGEIRLVGSEKPPFVL

SEQ ID NO: 358

MEKKRKVTLGFDLGIASVGWAIVDSETNQVYKLGSRLFDAPDTNLERRTQRGTRRLLRRRKYRN QKFYNLVKRTEVFGLSSREAIENRFRELS IKYP I IELKTKALSQEVCPDEIAWILHDYLKNRG YFYDEKETKEDFDQQTVESMPSYKLNEFYKKYGYFKGALSQPTESEMKDNKDLKEAFFFDFSNK EWLKEINYFFNVQK ILSETFIEEFKKIFSFTRDI SKGPGSDNMPSPYGIFGEFGDNGQGGRYE HIWDKNIGKCS IFTNEQRAPKYLPSALIFNFLNELANIRLYSTDKKNIQPLWKLSSVDKLNILL NLFNLPI SEKKKKLTST INDIVKKES IKS IMI SVEDIDMIKDEWAGKEPNVYGVGLSGL IEE SAKENKFKFQDLKILNVLINLLDNVGIKFEFKDRNDI IKNLELLDNLYLFLIYQKESNNKDSS I DLFIAKNESLNIENLKLKLKEFLLGAGNEFENHNSKTHSLSKKAIDEILPKLLDNNEGWNLEAI KNYDEEIKSQIEDNSSLMAKQDKKYLNDNFLKDAILPPNVKVTFQQAILIFNKI IQKFSKDFEI DKVVIELAREMTQDQENDALKGIAKAQKSKKSLVEERLEAN IDKSVFNDKYEKLIYKIFLWI S QDFKDPYTGAQI SVNEIVNNKVEIDHI IPYSLCFDDSSANKVLVHKQSNQEKSNSLPYEYIKQG HSGWNWDEFTKYVKRVFVNNVDS ILSKKERLKKSENLLTASYDGYDKLGFLARNLNDTRYATIL FRDQLNNYAEHHLIDNKKMFKVIAMNGAVTSFIRKNMSYDNKLRLKDRSDFSHHAYDAAIIALF SNKTKTLYNLIDPSLNGI I SKRSEGYWVIEDRYTGEIKELKKEDWTS IKNNVQARKIAKEIEEY LIDLDDEVFFSRKTKRKTNRQLYNETIYGIATKTDEDGITNYYKKEKFS ILDDKDIYLRLLRER EKFVINQSNPEVIDQI IEI IESYGKENNIPSRDEAINIKYTKNKINYNLYLKQYMRSLTKSLDQ FSEEFINQMIANKTFVLYNPTKNTTRKIKFLRLVNDVKINDIRKNQVINKFNGKNNEPKAFYEN INSLGAIVFKNSANNFKTLS INTQIAIFGDKNWDIEDFKTYNMEKIEKYKEIYGIDKTYNFHSF IFPGTILLDKQNKEFYYI SS IQTVRDI IEIKFLNKIEFKDENKNQDTSKTPKRLMFGIKS IMNN YEQVDI SPFGINKKIFE

SEQ ID NO: 359

MGYRIGLDVGITSTGYAVLKTDKNGLPYKILTLDSVIYPRAENPQTGASLAEPRRIKRGLRRRT RRTKFRKQRTQQLFIHSGLLSKPEIEQILATPQAKYSVYELRVAGLDRRLTNSELFRVLYFFIG HRGFKSNRKAELNPENEADKKQMGQLLNS IEEIRKAIAEKGYRTVGELYLKDPKYNDHKRNKGY IDGYLSTPNRQMLVDEIKQILDKQRELGNEKLTDEFYATYLLGDENRAGIFQAQRDFDEGPGAG PYAGDQIKKMVGKDIFEPTEDRAAKATYTFQYFNLLQKMTSLNYQNTTGDTWHTLNGLDRQAI I DAVFAKAEKPTKTYKPTDFGELRKLLKLPDDARFNLVNYGSLQTQKEIETVEKKTRFVDFKAYH DLVKVLPEEMWQSRQLLDHIGTALTLYSSDKRRRRYFAEELNLPAELIEKLLPLNFSKFGHLS I KSMQNI IPYLEMGQVYSEATTNTGYDFRKKQI SKDTIREEITNPVVRRAVTKTIKIVEQI IRRY GKPDGI IELARELGRNFKERGDIQKRQDKNRQTNDKIAAELTELGIPVNGQ I IRYKLHKEQN GVDPYTGDQIPFERAFSEGYEVDHI IPYS I SWDDSYTNKVLTSAKCNREKGNRIPMVYLANNEQ RLNALT IAD I IRNSRKRQKLLKQKLSDEELKDWKQR INDTRFITRVLYNYFRQAIEFNPEL EKKQRVLPLNGEVTSKIRSRWGFLKVREDGDLHHAIDATVIAAITPKFIQQVTKYSQHQEVKNN QALWHDAEIKDAEYAAEAQRMDADLFNKIFNGFPLPWPEFLDELLARI SDNPVEMMKSRSWNTY TPIEIAKLKPVFVVRLANHKI SGPAHLDTIRSAKLFDEKGIVLSRVS ITKLKINKKGQVATGDG IYDPENSNNGDKVVYSAIRQALEAHNGSGELAFPDGYLEYVDHGTKKLVRKVRVAKKVSLPVRL KNKAAADNGSMVRIDVFNTGKKFVFVPIYIKDTVEQVLPNKAIARGKSLWYQITESDQFCFSLY PGDMVHIESKTGIKPKYSNKENNTSVVPIKNFYGYFDGADIATAS ILVRAHDSSYTARS IGIAG LLKFEKYQVDYFGRYHKVHEKKRQLFVKRDE

SEQ ID NO: 360

MQKNINTKQNHIYIKQAQKIKEKLGDKPYRIGLDLGVGS IGFAIVSMEENDGNVLLPKEI IMVG SRIFKASAGAADRKLSRGQRNNHRHTRERMRYLWKVLAEQKLALPVPADLDRKENSSEGETSAK RFLGDVLQKDIYELRVKSLDERLSLQELGYVLYHIAGHRGSSAIRTFENDSEEAQKENTENKKI AG IKRLMAKKNYRTYGEYLYKEFFENKEKHKREKI SNAANNHKFSPTRDLVIKEAEAILKKQA GKDGFHKELTEEYIEKLTKAIGYESEKLIPESGFCPYLKDEKRLPASHKLNEERRLWETLNNAR YSDPIVDIVTGEITGYYEKQFTKEQKQKLFDYLLTGSELTPAQTKKLLGLKNTNFEDI ILQGRD KKAQKIKGYKLIKLESMPFWARLSEAQQDSFLYDWNSCPDEKLLTEKLSNEYHLTEEEIDNAFN EIVLSSSYAPLGKSAMLI ILEKIKNDLSYTEAVEEALKEGKLTKEKQAIKDRLPYYGAVLQEST QKI IAKGFSPQFKDKGYKTPHTNKYELEYGRIANPVVHQTLNELRKLVNEI IDILGKKPCEIGL ETARELKKSAEDRSKLSREQNDNESNRNRIYEIYIRPQQQVI ITRRENPRNYILKFELLEEQKS QCPFCGGQI SPNDI INNQADIEHLFPIAESEDNGRNNLVI SHSACNADKAKRSPWAAFASAAKD SKYDYNRILSNVKE IPHKAWRFNQGAFEKFIENKPMAARFKTDNSYI SKVAHKYLACLFEKPN IICVKGSLTAQLRMAWGLQGLMIPFAKQLITEKESESFNKDVNSNKKIRLDNRHHALDAIVIAY ASRGYGNLLNKMAGKDYKINYSERNWLSKILLPPNNIVWENIDADLESFESSVKTALKNAFISV KHDHSDNGELVKGTMYKIFYSERGYTLTTYKKLSALKLTDPQKKKTPKDFLETALLKFKGRESE MKNEKIKSAIENNKRLFDVIQDNLEKAKKLLEEENEKSKAEGKKEKNINDAS IYQKAI SLSGDK YVQLSKKEPGKFFAI SKPTPTTTGYGYDTGDSLCVDLYYDNKGKLCGEI IRKIDAQQKNPLKYK EQGFTLFERIYGGDILEVDFDIHSDKNSFRNNTGSAPENRVFIKVGTFTEITNNNIQIWFGNI I KSTGGQDDSFTINSMQQYNPRKLILSSCGFIKYRSPILKNKEG

SEQ ID NO: 361

MAAFKPNPINYILGLDIGIASVGWAMVEIDEDENPICLIDLGVRVFERAEVPKTGDSLAMARRL ARSVRRLTRRRAHRLLRARRLLKREGVLQAADFDENGLIKSLPNTPWQLRAAALDRKLTPLEWS AVLLHLIKHRGYLSQRKNEGETADKELGALLKGVADNAHALQTGDFRTPAELALNKFEKESGHI RNQRGDYSHTFSRKDLQAELILLFEKQKEFGNPHVSGGLKEGIETLLMTQRPALSGDAVQKMLG HCTFEPAEPKAAKNTYTAERFIWLTKLNNLRILEQGSERPLTDTERATLMDEPYRKSKLTYAQA RKLLGLEDTAFFKGLRYGKDNAEASTLMEMKAYHAI SRALEKEGLKDKKSPLNLSPELQDEIGT AFSLFKTDEDITGRLKDRIQPEILEALLKHI SFDKFVQI SLKALRRIVPLMEQGKRYDEACAEI YGDHYGKKNTEEKIYLPPIPADEIRNPVVLRALSQARKVINGVVRRYGSPARIHIETAREVGKS FKDRKEIEKRQEENRKDREKAAAKFREYFPNFVGEPKSKDILKLRLYEQQHGKCLYSGKEINLG RLNEKGYVEIDHALPFSRTWDDSFNNKVLVLGSENQNKGNQTPYEYFNGKDNSREWQEFKARVE TSRFPRSKKQRILLQKFDEDGFKERNLNDTRYVNRFLCQFVADRMRLTGKGKKRVFASNGQITN LLRGFWGLRKVRAENDRHHALDAVVVACSTVAMQQKITRFVRYKEMNAFDGKTIDKETGEVLHQ KTHFPQPWEFFAQEVMIRVFGKPDGKPEFEEADTPEKLRTLLAEKLSSRPEAVHEYVTPLFVSR APNRKMSGQGHMETVKSAKRLDEGVSVLRVPLTQLKLKDLEKMVNREREPKLYEALKARLEAHK DDPAKAFAEPFYKYDKAGNRTQQVKAVRVEQVQKTGVWVRNHNGIADNATMVRVDVFEKGDKYY LVPIYSWQVAKGILPDRAVVQGKDEEDWQLIDDSFNFKFSLHPNDLVEVITKKARMFGYFASCH RGTGNINIRIHDLDHKIGKNGILEGIGVKTALSFQKYQIDELGKEIRPCRLKKRPPVR

SEQ ID NO: 362

MQTTNLSYILGLDLGIASVGWAVVEINENEDPIGLIDVGVRIFERAEVPKTGESLALSRRLARS TRRLIRRRAHRLLLAKRFLKREGILSTIDLEKGLPNQAWELRVAGLERRLSAIEWGAVLLHLIK HRGYLSKRKNESQTNNKELGALLSGVAQNHQLLQSDDYRTPAELALKKFAKEEGHIRNQRGAYT HTFNRLDLLAELNLLFAQQHQFGNPHCKEHIQQYMTELLMWQKPALSGEAILKMLGKCTHEKNE FKAAKHTYSAERFVWLTKLNNLRILEDGAERALNEEERQLLINHPYEKSKLTYAQVRKLLGLSE QAIFKHLRYSKENAESATFMELKAWHAIRKALENQGLKDTWQDLAKKPDLLDEIGTAFSLYKTD EDIQQYLTNKVPNSVINALLVSLNFDKFIELSLKSLRKILPLMEQGKRYDQACREIYGHHYGEA NQKTSQLLPAIPAQEIRNPVVLRTLSQARKVINAI IRQYGSPARVHIETGRELGKSFKERREIQ KQQEDNRTKRESAVQKFKELFSDFSSEPKSKDILKFRLYEQQHGKCLYSGKEINIHRLNEKGYV EIDHALPFSRTWDDSFNNKVLVLASENQNKGNQTPYEWLQGKINSERWKNFVALVLGSQCSAAK KQRLLTQVIDDNKFIDRNLNDTRYIARFLSNYIQENLLLVGKNKKNVFTPNGQITALLRSRWGL IKARENNNRHHALDAIVVACATPSMQQKITRFIRFKEVHPYKIENRYEMVDQESGEI I SPHFPE PWAYFRQEVNIRVFDNHPDTVLKEMLPDRPQANHQFVQPLFVSRAPTRKMSGQGHMETIKSAKR LAEGI SVLRIPLTQLKPNLLENMVNKEREPALYAGLKARLAEFNQDPAKAFATPFYKQGGQQVK AIRVEQVQKSGVLVRENNGVADNAS IVRTDVFIKNNKFFLVPIYTWQVAKGILPNKAIVAHKNE DEWEEMDEGAKFKFSLFPNDLVELKTKKEYFFGYYIGLDRATG I SLKEHDGEI SKGKDGVYRV GVKLALSFEKYQVDELGKNRQICRPQQRQPVR

SEQ ID NO: 363

MGIRFAFDLGTNS IGWAVWRTGPGVFGEDTAASLDGSGVLIFKDGRNPKDGQSLATMRRVPRQS RKRRDRFVLRRRDLLAALRKAGLFPVDVEEGRRLAATDPYHLRAKALDESLTPHEMGRVIFHLN QRRGFRSNRKADRQDREKGKIAEGSKRLAETLAATNCRTLGEFLWSRHRGTPRTRSPTRIRMEG EGAKALYAFYPTREMVRAEFERLWTAQSRFAPDLLTPERHEEIAGILFRQRDLAPPKIGCCTFE PSERRLPRALPSVEARGIYERLAHLRITTGPVSDRGLTRPERDVLASALLAGKSLTFKAVRKTL KILPHALVNFEEAGEKGLDGALTAKLLSKPDHYGAAWHGLSFAEKDTFVGKLLDEADEERLIRR LVTENRLSEDAARRCAS IPLADGYGRLGRTANTEILAALVEETDETGTVVTYAEAVRRAGERTG RNWHHSDERDGVILDRLPYYGEILQRHVVPGSGEPEEKNEAARWGRLANPTVHIGLNQLRKVVN RLIAAHGRPDQIVVELARELKLNREQKERLDRENRKNREENERRTAILAEHGQRDTAENKIRLR LFEEQARANAGIALCPYTGRAIGIAELFTSEVEIDHILPVSLTLDDSLANRVLCRREANREKRR QTPFQAFGATPAWNDIVARAAKLPPNKRWRFDPAALERFEREGGFLGRQLNETKYLSRLAKIYL GKICDPDRVYVTPGTLTGLLRARWGLNS ILSDSNFKNRSDHRHHAVDAVVIGVLTRGMIQRIAH DAARAEDQDLDRVFRDVPVPFEDFRDHVRERVSTITVAVKPEHGKGGALHEDTSYGLVPDTDPN AALGNLVVRKPIRSLTAGEVDRVRDRALRARLGALAAPFRDESGRVRDAKGLAQALEAFGAENG IRRVRILKPDASVVTIADRRTGVPYRAVAPGENHHVDIVQMRDGSWRGFAASVFEVNRPGWRPE WEVKKLGGKLVMRLHKGDMVELSDKDGQRRVKVVQQIEI SANRVRLSPHNDGGKLQDRHADADD PFRWDLATIPLLKDRGCVAVRVDPIGVVTLRRSNV

SEQ ID NO: 364

MMEVFMGRLVLGLDIGITSVGFGI IDLDESEIVDYGVRLFKEGTAAENETRRTKRGGRRLKRRR VTRREDMLHLLKQAGI I STSFHPLNNPYDVRVKGLNERLNGEELATALLHLCKHRGSSVETIED DEAKAKEAGETKKVLSMNDQLLKSGKYVCEIQKERLRTNGHIRGHENNFKTRAYVDEAFQILSH QDLSNELKSAI ITI I SRKRMYYDGPGGPLSPTPYGRYTYFGQKEPIDLIEKMRGKCSLFPNEPR APKLAYSAELFNLLNDLNNLS IEGEKLTSEQKAMILKIVHEKGKITPKQLAKEVGVSLEQIRGF RIDTKGSPLLSELTGYKMIREVLEKSNDEHLEDHVFYDEIAEILTKTKDIEGRKKQI SELSSDL NEESVHQLAGLTKFTAYHSLSFKALRLINEEMLKTELNQMQS ITLFGLKQNNELSVKGMK IQA DDTAILSPVAKRAQRETFKVVNRLREIYGEFDS IVVEMAREKNSEEQRKAIRERQKFFEMRNKQ VADI IGDDRKINAKLREKLVLYQEQDGKTAYSLEPIDLKLLIDDPNAYEVDHI IPI S I SLDDS I TNKVLVTHRENQEKGNLTPI SAFVKGRFTKGSLAQYKAYCLKLKEK IKTNKGYRKKVEQYLLN ENDIYKYDIQKEFINRNLVDTSYASRVVLNTLTTYFKQNEIPTKVFTVKGSLTNAFRRKINLKK DRDEDYGHHAIDALI IASMPKMRLLSTIFSRYKIEDIYDESTGEVFSSGDDSMYYDDRYFAFIA SLKAIKVRKFSHKIDTKPNRSVADETIYSTRVIDGKEKVVKKYKDIYDPKFTALAEDILNNAYQ EKYLMALHDPQTFDQIVKVVNYYFEEMSKSEKYFTKDKKGRIKI SGMNPLSLYRDEHGMLKKYS KKGDGPAITQMKYFDGVLGNHIDI SAHYQVRDKKVVLQQI SPYRTDFYYSKENGYKFVTIRYKD VRWSEKKKKYVIDQQDYAMKKAEKKIDDTYEFQFSMHRDELIGITKAEGEALIYPDETWHNFNF FFHAGETPEILKFTATNNDKSNKIEVKPIHCYCKMRLMPTI SKKIVRIDKYATDVVGNLYKVKK NTLKFEFD

SEQ ID NO: 365

MKKILGVDLGITSFGYAILQETGKDLYRCLDNSVVMRNNPYDEKSGESSQS IRSTQKSMRRLIE KRKKRIRCVAQTMERYGILDYSETMKINDPKNNPIKNRWQLRAVDAWKRPLSPQELFAIFAHMA KHRGYKS IATEDLIYELELELGLNDPEKESEKKADERRQVYNALRHLEELRKKYGGETIAQTIH RAVEAGDLRSYRNHDDYEKMIRREDIEEEIEKVLLRQAELGALGLPEEQVSELIDELKACITDQ EMPTIDESLFGKCTFYKDELAAPAYSYLYDLYRLYKKLADLNIDGYEVTQEDREKVIEWVEKKI AQGKNLKKITHKDLRKILGLAPEQKIFGVEDERIVKGKKEPRTFVPFFFLADIAKFKELFASIQ KHPDALQIFRELAEILQRSKTPQEALDRLRALMAGKGIDTDDRELLELFKNKRSGTRELSHRYI LEALPLFLEGYDEKEVQRILGFDDREDYSRYPKSLRHLHLREGNLFEKEENPINNHAVKSLASW ALGLIADLSWRYGPFDEI ILETTRDALPEKIRKEIDKAMREREKALDKI IGKYKKEFPS IDKRL ARKIQLWERQKGLDLYSGKVINLSQLLDGSADIEHIVPQSLGGLSTDYNTIVTLKSVNAAKGNR LPGDWLAGNPDYRERIGMLSEKGLIDWKKRKNLLAQSLDEIYTENTHSKGIRATSYLEALVAQV LKRYYPFPDPELRKNGIGVRMIPGKVTSKTRSLLGIKSKSRETNFHHAEDALILSTLTRGWQNR LHRMLRDNYGKSEAELKELWKKYMPHIEGLTLADYIDEAFRRFMSKGEESLFYRDMFDTIRS I S YWVDKKPLSASSHKETVYSSRHEVPTLRKNILEAFDSLNVIKDRHKLTTEEFMKRYDKEIRQKL WLHRIGNTNDESYRAVEERATQIAQILTRYQLMDAQNDKEIDEKFQQALKELITSPIEVTGKLL RKMRFVYDKLNAMQIDRGLVETDKNMLGIHI SKGPNEKLIFRRMDVNNAHELQKERSGILCYLN EMLFIFNKKGLIHYGCLRSYLEKGQGSKYIALFNPRFPANPKAQPSKFTSDSKIKQVGIGSATG I IKAHLDLDGHVRSYEVFGTLPEGS IEWFKEESGYGRVEDDPHH

SEQ ID NO: 366

MRPIEPWILGLDIGTDSLGWAVFSCEEKGPPTAKELLGGGVRLFDSGRDAKDHTSRQAERGAFR RARRQTRTWPWRRDRLIALFQAAGLTPPAAETRQIALALRREAVSRPLAPDALWAALLHLAHHR GFRSNRIDKRERAAAKALAKAKPAKATAKATAPAKEADDEAGFWEGAEAALRQRMAASGAPTVG ALLADDLDRGQPVRMRYNQSDRDGVVAPTRALIAEELAEIVARQSSAYPGLDWPAVTRLVLDQR PLRSKGAGPCAFLPGEDRALRALPTVQDFI IRQTLANLRLPSTSADEPRPLTDEEHAKALALLS TARFVEWPALRRALGLKRGVKFTAETERNGAKQAARGTAGNLTEAILAPLIPGWSGWDLDRKDR VFSDLWAARQDRSALLALIGDPRGPTRVTEDETAEAVADAIQIVLPTGRASLSAKAARAIAQAM APGIGYDEAVTLALGLHHSHRPRQERLARLPYYAAALPDVGLDGDPVGPPPAEDDGAAAEAYYG RIGNI SVHIALNETRKIVNALLHRHGPILRLVMVETTRELKAGADERKRMIAEQAERERENAEI DVELRKSDRWMANARERRQRVRLARRQNNLCPYTSTPIGHADLLGDAYDIDHVIPLARGGRDSL DNMVLCQSDANKTKGDKTPWEAFHDKPGWIAQRDDFLARLDPQTAKALAWRFADDAGERVARKS AEDEDQGFLPRQLTDTGYIARVALRYLSLVTNEPNAVVATNGRLTGLLRLAWDITPGPAPRDLL PTPRDALRDDTAARRFLDGLTPPPLAKAVEGAVQARLAALGRSRVADAGLADALGLTLASLGGG GKNRADHRHHFIDAAMIAVTTRGLINQINQASGAGRILDLRKWPRTNFEPPYPTFRAEVMKQWD HIHPS IRPAHRDGGSLHAATVFGVRNRPDARVLVQRKPVEKLFLDANAKPLPADKIAEI IDGFA SPRMAKRFKALLARYQAAHPEVPPALAALAVARDPAFGPRGMTANTVIAGRSDGDGEDAGLITP FRANPKAAVRTMGNAVYEVWEIQVKGRPRWTHRVLTRFDRTQPAPPPPPENARLVMRLRRGDLV YWPLESGDRLFLVKKMAVDGRLALWPARLATGKATALYAQLSCPNINLNGDQGYCVQSAEGIRK EKIRTTSCTALGRLRLSKKAT

SEQ ID NO: 367

MKYTLGLDVGIASVGWAVIDKDNNKI IDLGVRCFDKAEESKTGESLATARRIARGMRRRI SRRS QRLRLVKKLFVQYEI IKDSSEFNRIFDTSRDGWKDPWELRYNALSRILKPYELVQVLTHITKRR GFKSNRKEDLSTTKEGVVITS IKNNSEMLRTKNYRTIGEMIFMETPENSNKRNKVDEYIHTIAR EDLLNEIKYIFS IQRKLGSPFVTEKLEHDFLNIWEFQRPFASGDS ILSKVGKCTLLKEELRAPT SCYTSEYFGLLQS INNLVLVEDNNTLTLNNDQRAKI IEYAHFKNEIKYSEIRKLLDIEPEILFK AHNLTHKNPSGNNESKKFYEMKSYHKLKSTLPTDIWGKLHSNKESLDNLFYCLTVYKNDNEIKD YLQANNLDYLIEYIAKLPTFNKFKHLSLVAMKRI IPFMEKGYKYSDACNMAELDFTGSSKLEKC NKLTVEPI IENVTNPVVIRALTQARKVINAI IQKYGLPYMV IELAREAGMTRQDRDNLKKEHE NNRKAREKI SDLIRQNGRVASGLDILKWRLWEDQGGRCAYSGKPIPVCDLLNDSLTQIDHIYPY SRSMDDSYMNKVLVLTDENQNKRSYTPYEVWGSTEKWEDFEARIYSMHLPQSKEKRLLNRNFIT KDLDSFI SRNLNDTRYI SRFLKNYIESYLQFSNDSPKSCVVCVNGQCTAQLRSRWGLNKNREES DLHHALDAAVIACADRKI IKEITNYYNERENHNYKVKYPLPWHSFRQDLMETLAGVFI SRAPRR KITGPAHDETIRSPKHFNKGLTSVKIPLTTVTLEKLETMVKNTKGGI SDKAVYNVLKNRLIEHN NKPLKAFAEKIYKPLKNGTNGAI IRS IRVETPSYTGVFRNEGKGI SDNSLMVRVDVFKKKDKYY LVPIYVAHMIKKELPSKAIVPLKPESQWELIDSTHEFLFSLYQNDYLVIKTKKGITEGYYRSCH RGTGSLSLMPHFANNKNVKIDIGVRTAI S IEKYNVDILGNKS IVKGEPRRGMEKYNSFKSN

SEQ ID NO: 368

MIRTLGIDIGIAS IGWAVIEGEYTDKGLENKEIVASGVRVFTKAENPKNKESLALPRTLARSAR RRNARKKGRIQQVKHYLSKALGLDLECFVQGEKLATLFQTSKDFLSPWELRERALYRVLDKEEL ARVILHIAKRRGYDDITYGVEDNDSGKIKKAIAENSKRIKEEQCKTIGEMMYKLYFQKSLNVRN KKESYNRCVGRSELREELKTIFQIQQELKSPWVNEELIYKLLGNPDAQSKQEREGLIFYQRPLK GFGDKIGKCSHIKKGENSPYRACKHAPSAEEFVALTKS INFLKNLTNRHGLCFSQEDMCVYLGK ILQEAQKNEKGLTYSKLKLLLDLPSDFEFLGLDYSGKNPEKAVFLSLPSTFKLNKITQDRKTQD KIANILGANKDWEAILKELESLQLSKEQIQTIKDAKLNFSKHINLSLEALYHLLPLMREGKRYD EGVEILQERGIFSKPQPKNRQLLPPLSELAKEESYFDIPNPVLRRALSEFRKVVNALLEKYGGF HYFHIELTRDVCKAKSARMQLEKINKKNKSENDAASQLLEVLGLPNTYNNRLKCKLWKQQEEYC LYSGEKITIDHLKDQRALQIDHAFPLSRSLDDSQSNKVLCLTSSNQEKSNKTPYEWLGSDEKKW DMYVGRVYSSNFSPSKKRKLTQKNFKERNEEDFLARNLVDTGYIGRVTKEYIKHSLSFLPLPDG KKEHIRI I SGSMTSTMRSFWGVQEKNRDHHLHHAQDAI I IACIEPSMIQKYTTYLKDKETHRLK SHQKAQILREGDHKLSLRWPMSNFKDKIQES IQNI IPSHHVSHKVTGELHQETVRTKEFYYQAF GGEEGVKKALKFGKIREINQGIVDNGAMVRVDIFKSKDKGKFYAVPIYTYDFAIGKLPNKAIVQ GKKNGI IKDWLEMDENYEFCFSLFKNDCIKIQTKEMQEAVLAIYKSTNSAKATIELEHLSKYAL KNEDEEKMFTDTDKEKNKTMTRESCGIQGLKVFQKVKLSVLGEVLEHKPRNRQNIALKTTPKHV SEQ ID NO: 369

MKYS IGLDIGIASVGWSVINKDKERIEDMGVRIFQKAENPKDGSSLASSRREKRGSRRRNRRKK HRLDRIK ILCESGLVKKNEIEKIYKNAYLKSPWELRAKSLEAKI SNKEIAQILLHIAKRRGFK SFRKTDRNADDTGKLLSGIQENKKIMEEKGYLTIGDMVAKDPKFNTHVRNKAGSYLFSFSRKLL EDEVRKIQAKQKELGNTHFTDDVLEKYIEVFNSQRNFDEGPSKPSPYYSEIGQIAKMIGNCTFE SSEKRTAKNTWSGERFVFLQKLNNFRIVGLSGKRPLTEEERDIVEKEVYLKKEVRYEKLRKILY LKEEERFGDLNYSKDEKQDKKTEKTKFISLIGNYTIKKLNLSEKLKSEIEEDKSKLDKI IEILT FNKSDKTIESNLKKLELSREDIEILLSEEFSGTLNLSLKAIKKILPYLEKGLSYNEACEKADYD YKNNGIKFKRGELLPVVDKDLIANPVVLRAI SQTRKVVNAI IRKYGTPHTIHVEVARDLAKSYD DRQTI IKENKKRELENEKTKKFI SEEFGIKNVKGKLLLKYRLYQEQEGRCAYSRKELSLSEVIL DESMTDIDHI IPYSRSMDDSYSNKVLVLSGENRKKSNLLPKEYFDRQGRDWDTFVLNVKAMKIH PRKKSNLLKEKFTREDNKDWKSRALNDTRYI SRFVANYLENALEYRDDSPKKRVFMIPGQLTAQ LRARWRLNKVRENGDLHHALDAAVVAVTDQKAINNI SNI SRYKELKNCKDVIPS IEYHADEETG EVYFEEVKDTRFPMPWSGFDLELQKRLESENPREEFYNLLSDKRYLGWFNYEEGFIEKLRPVFV SRMPNRGVKGQAHQETIRSSKKI SNQIAVSKKPLNS IKLKDLEKMQGRDTDRKLYEALKNRLEE YDDKPEKAFAEPFYKPTNSGKRGPLVRGIKVEEKQNVGVYVNGGQASNGSMVRIDVFRKNGKFY TVPIYVHQTLLKELPNRAINGKPYKDWDLIDGSFEFLYSFYPNDLIEIEFGKSKS IKNDNKLTK TEIPEVNLSEVLGYYRGMDTSTGAATIDTQDGKIQMRIGIKTVKNIKKYQVDVLGNVYKVKREK RQTF

SEQ ID NO: 370

MSKKVSRRYEEQAQEICQRLGSRPYS IGLDLGVGS IGVAVAAYDPIKKQPSDLVFVSSRIFIPS TGAAERRQKRGQRNSLRHRANRLKFLWKLLAERNLMLSYSEQDVPDPARLRFEDAVVRANPYEL RLKGLNEQLTLSELGYALYHIANHRGSSSVRTFLDEEKSSDDKKLEEQQAMTEQLAKEKGI STF IEVLTAFNTNGLIGYRNSESVKSKGVPVPTRDI I SNEIDVLLQTQKQFYQEILSDEYCDRIVSA ILFENEKIVPEAGCCPYFPDEKKLPRCHFLNEERRLWEAINNARIKMPMQEGAAKRYQSASFSD EQRHILFHIARSGTDITPKLVQKEFPALKTS I IVLQGKEKAIQKIAGFRFRRLEEKSFWKRLSE EQKDDFFSAWTNTPDDKRLSKYLMKHLLLTENEVVDALKTVSLIGDYGPIGKTATQLLMKHLED GLTYTEALERGMETGEFQELSVWEQQSLLPYYGQILTGSTQALMGKYWHSAFKEKRDSEGFFKP NTNSDEEKYGRIANPVVHQTLNELRKLMNELITILGAKPQEITVELARELKVGAEKREDI IKQQ TKQEKEAVLAYSKYCEPNNLDKRYIERFRLLEDQAFVCPYCLEHI SVADIAAGRADVDHIFPRD DTADNSYGNKVVAHRQCNDIKGKRTPYAAFSNTSAWGPIMHYLDETPGMWRKRRKFETNEEEYA KYLQSKGFVSRFESDNSYIAKAAKEYLRCLFNPNNVTAVGSLKGMETS ILRKAWNLQGIDDLLG SRHWSKDADTSPTMRKNRDDNRHHGLDAIVALYCSRSLVQMINTMSEQGKRAVEIEAMIPIPGY ASEPNLSFEAQRELFRKKILEFMDLHAFVSMKTDNDANGALLKDTVYS ILGADTQGEDLVFVVK KKIKDIGVKIGDYEEVASAIRGRITDKQPKWYPMEMKDKIEQLQSKNEAALQKYKESLVQAAAV LEESNRKLIESGKKPIQLSEKTI SKKALELVGGYYYLI SNNKRTKTFVVKEPSNEVKGFAFDTG SNLCLDFYHDAQGKLCGEI IRKIQAMNPSYKPAYMKQGYSLYVRLYQGDVCELRASDLTEAESN LAKTTHVRLPNAKPGRTFVI I ITFTEMGSGYQIYFSNLAKSKKGQDTSFTLTTIKNYDVRKVQL SSAGLVRYVSPLLVDKIEKDEVALCGE

SEQ ID NO: 371

MNQKFILGLDIGITSVGYGLIDYETKNI IDAGVRLFPEANVENNEGRRSKRGSRRLKRRRIHRL ERVKKLLEDYNLLDQSQIPQSTNPYAIRVKGLSEALSKDELVIALLHIAKRRGIHKIDVIDSND DVGNELSTKEQLNKNSKLLKDKFVCQIQLERMNEGQVRGEKNRFKTADI IKEI IQLLNVQKNFH QLDENFINKYIELVEMRREYFEGPGKGSPYGWEGDPKAWYETLMGHCTYFPDELRSVKYAYSAD LFNALNDLNNLVIQRDGLSKLEYHEKYHI IENVFKQKKKPTLKQIANEINVNPEDIKGYRITKS GKPQFTEFKLYHDLKSVLFDQS ILENEDVLDQIAEILTIYQDKDS IKSKLTELDILLNEEDKEN IAQLTGYTGTHRLSLKCIRLVLEEQWYSSRNQMEIFTHLNIKPKKINLTAANKIPKAMIDEFIL SPVVKRTFGQAINLINKI IEKYGVPEDI I IELARENNSKDKQKFINEMQKKNENTRKRINEI IG KYGNQNAKRLVEKIRLHDEQEGKCLYSLES IPLEDLLNNPNHYEVDHI IPRSVSFDNSYHNKVL VKQSENSKKSNLTPYQYFNSGKSKLSYNQFKQHILNLSKSQDRI SKKKKEYLLEERDINKFEVQ KEFINRNLVDTRYATRELTNYLKAYFSANNMNVKVKTINGSFTDYLRKVWKFKKERNHGYKHHA EDALI IA ADFLFKENKKLKAVNSVLEKPEIESKQLDIQVDSEDNYSEMFI IPKQVQDIKDFRN FKYSHRVDKKPNRQLINDTLYSTRKKDNSTYIVQTIKDIYAKDNTTLKKQFDKSPEKFLMYQHD PRTFEKLEVIMKQYANEKNPLAKYHEETGEYLTKYSKKNNGPIVKSLKYIGNKLGSHLDVTHQF KSSTKKLVKLS IKPYRFDVYLTDKGYKFITI SYLDVLKKDNYYYIPEQKYDKLKLGKAIDKNAK FIASFYKNDLIKLDGEIYKI IGVNSDTRNMIELDLPDIRYKEYCELN IKGEPRIKKTIGKKVN SIEKLTTDVLGNVFTNTQYTKPQLLFKRGN

SEQ ID NO: 372

MIMKLEKWRLGLDLGTNS IGWSVFSLDKDNSVQDLIDMGVRIFSDGRDPKTKEPLAVARRTARS QRKLIYRRKLRRKQVFKFLQEQGLFPKTKEECMTLKSLNPYELRIKALDEKLEPYELGRALFNL AVRRGFKSNRKDGSREEVSEKKSPDEIKTQADMQTHLEKAIKENGCRTITEFLYKNQGENGGIR FAPGRMTYYPTRKMYEEEFNLIRSKQEKYYPQVDWDDIYKAIFYQRPLKPQQRGYCIYENDKER TFKAMPCSQKLRILQDIGNLAYYEGGSKKRVELNDNQDKVLYELLNSKDKVTFDQMRKALCLAD SNSFNLEENRDFLIGNPTAVKMRSKNRFGKLWDEIPLEEQDLI IETI ITADEDDAVYEVIKKYD LTQEQRDFIVKNTILQSGTSMLCKEVSEKLVKRLEEIADLKYHEAVESLGYKFADQTVEKYDLL PYYGKVLPGSTMEIDLSAPETNPEKHYGKI SNPTVHVALNQTRVVV ALIKEYGKPSQIAIELS RDLKNNVEKKAEIARKQNQRAKENIAINDTI SALYHTAFPGKSFYPNRNDRMKYRLWSELGLGN KCIYCGKGI SGAELFTKEIEIEHILPFSRTLLDAESNLTVAHSSCNAFKAERSPFEAFGTNPSG YSWQEI IQRANQLKNTSKKNKFSPNAMDSFEKDSSFIARQLSDNQYIAKAALRYLKCLVENPSD VWTTNGSMTKLLRDKWEMDS ILCRKFTEKEVALLGLKPEQIGNYKKNRFDHRHHAIDAVVIGLT DRSMVQKLATKNSHKGNRIEIPEFPILRSDLIEKVKNIVVSFKPDHGAEGKLSKETLLGKIKLH GKETFVCRENIVSLSEKNLDDIVDEIKSKVKDYVAKHKGQKIEAVLSDFSKENGIKKVRCVNRV QTPIEITSGKI SRYLSPEDYFAAVIWEIPGEKKTFKAQYIRRNEVEKNSKGLNVVKPAVLENGK PHPAAKQVCLLHKDDYLEFSDKGKMYFCRIAGYAATNNKLDIRPVYAVSYCADWINSTNETMLT GYWKPTPTQNWVSVNVLFDKQKARLVTVSPIGRVFRK

SEQ ID NO: 373

MSSKAIDSLEQLDLFKPQEYTLGLDLGIKS IGWAILSGERIANAGVYLFETAEELNSTGNKLI S KAAERGRKRRIRRMLDRKARRGRHIRYLLEREGLPTDELEEVVVHQSNRTLWDVRAEAVERKLT KQELAAVLFHLVRHRGYFPNTKKLPPDDESDSADEEQGKINRATSRLREELKASDCKTIGQFLA QNRDRQRNREGDYSNLMARKLVFEEALQILAFQRKQGHELSKDFEKTYLDVLMGQRSGRSPKLG NCSLIPSELRAPSSAPSTEWFKFLQNLGNLQI SNAYREEWS IDAPRRAQI IDACSQRSTSSYWQ IRRDFQIPDEYRFNLVNYERRDPDVDLQEYLQQQERKTLANFRNWKQLEKI IGTGHPIQTLDEA ARLITLIKDDEKLSDQLADLLPEASDKAITQLCELDFTTAAKI SLEAMYRILPHMNQGMGFFDA CQQESLPEIGVPPAGDRVPPFDEMYNPVVNRVLSQSRKLINAVIDEYGMPAKIRVELARDLGKG RELRERIKLDQLDKSKQNDQRAEDFRAEFQQAPRGDQSLRYRLWKEQNCTCPYSGRMIPVNSVL SEDTQIDHILPI SQSFDNSLSNKVLCFTEENAQKSNRTPFEYLDAADFQRLEAI SGNWPEAKRN KLLHKSFGKVAEEWKSRALNDTRYLTSALADHLRHHLPDSKIQTVNGRITGYLRKQWGLEKDRD KHTHHAVDAIVVACTTPAIVQQVTLYHQDIRRYKKLGEKRPTPWPETFRQDVLDVEEEIFITRQ PKKVSGGIQTKDTLRKHRSKPDRQRVALTKVKLADLERLVEKDASNRNLYEHLKQCLEESGDQP TKAFKAPFYMPSGPEAKQRPILSKVTLLREKPEPPKQLTELSGGRRYDSMAQGRLDIYRYKPGG KRKDEYRVVLQRMIDLMRGEENVHVFQKGVPYDQGPEIEQNYTFLFSLYFDDLVEFQRSADSEV IRGYYRTFNIANGQLKI STYLEGRQDFDFFGANRLAHFAKVQVNLLGKVIK

SEQ ID NO: 374

MRSLRYRLALDLGSTSLGWALFRLDACNRPTAVIKAGVRIFSDGRNPKDGSSLAVTRRAARAMR RRRDRLLKRKTRMQAKLVEHGFFPADAGKRKALEQLNPYALRAKGLQEALLPGEFARALFHINQ RRGFKSNRKTDKKDNDSGVLKKAIGQLRQQMAEQGSRTVGEYLWTRLQQGQGVRARYREKPYTT EEGKKRIDKSYDLYIDRAMIEQEFDALWAAQAAFNPTLFHEAARADLKDTLLHQRPLRPVKPGR CTLLPEEERAPLALPSTQRFRIHQEVNHLRLLDENLREVALTLAQRDAVVTALETKAKLSFEQI RKLLKLSGSVQFNLEDAKRTELKGNATSAALARKELFGAAWSGFDEALQDEIVWQLVTEEGEGA LIAWLQTHTGVDEARAQAIVDVSLPEGYGNLSRKALARIVPALRAAVITYDKAVQAAGFDHHSQ LGFEYDASEVEDLVHPETGEIRSVFKQLPYYGKALQRHVAFGSGKPEDPDEKRYGKIANPTVHI GLNQVRMVVNALIRRYGRPTEVVIELARDLKQSREQKVEAQRRQADNQRRNARIRRS IAEVLGI GEERVRGSDIQKWICWEELSFDAADRRCPYSGVQI SAAMLLSDEVEVEHILPFSKTLDDSLNNR TVAMRQANRIKRNRTPWDARAEFEAQGWSYEDILQRAERMPLRKRYRFAPDGYERWLGDDKDFL ARALNDTRYLSRVAAEYLRLVCPGTRVIPGQLTALLRGKFGLNDVLGLDGEKNRNDHRHHAVDA CVIGVTDQGLMQRFATASAQARGDGLTRLVDGMPMPWPTYRDHVERAVRHIWVSHRPDHGFEGA MMEETSYGIRKDGS IKQRRKADGSAGREI SNLIRIHEATQPLRHGVSADGQPLAYKGYVGGSNY CIEITVNDKGKWEGEVI STFRAYGVVRAGGMGRLRNPHEGQNGRKLIMRLVIGDSVRLEVDGAE RTMRIVKI SGSNGQIFMAPIHEANVDARNTDKQDAFTYTSKYAGSLQKAKTRRVTI SPIGEVRD PGFKG

SEQ ID NO: 375

MARPAFRAPRREHVNGWTPDPHRI SKPFFILVSWHLLSRVVIDSSSGCFPGTSRDHTDKFAEWE CAVQPYRLSFDLGTNS IGWGLLNLDRQGKPREIRALGSRIFSDGRDPQDKASLAVARRLARQMR RRRDRYLTRRTRLMGALVRFGLMPADPAARKRLEVAVDPYLARERATRERLEPFEIGRALFHLN QRRGYKPVRTATKPDEEAGKVKEAVERLEAAIAAAGAPTLGAWFAWRKTRGETLRARLAGKGKE AAYPFYPARRMLEAEFDTLWAEQARHHPDLLTAEAREILRHRIFHQRPLKPPPVGRCTLYPDDG RAPRALPSAQRLRLFQELASLRVIHLDLSERPLTPAERDRIVAFVQGRPPKAGRKPGKVQKSVP FEKLRGLLELPPGTGFSLESDKRPELLGDETGARIAPAFGPGWTALPLEEQDALVELLLTEAEP ERAIAALTARWALDEATAAKLAGATLPDFHGRYGRRAVAELLPVLERETRGDPDGRVRPIRLDE AVKLLRGGKDHSDFSREGALLDALPYYGAVLERHVAFGTGNPADPEEKRVGRVANPTVHIALNQ LRHLVNAILARHGRPEEIVIELARDLKRSAEDRRREDKRQADNQKRNEERKRLILSLGERPTPR NLLKLRLWEEQGPVENRRCPYSGETI SMRMLLSEQVDIDHILPFSVSLDDSAANKVVCLREANR IKRNRSPWEAFGHDSERWAGILARAEALPKNKRWRFAPDALEKLEGEGGLRARHLNDTRHLSRL AVEYLRCVCPKVRVSPGRLTALLRRRWGIDAILAEADGPPPEVPAETLDPSPAEKNRADHRHHA LDAVVIGCIDRSMVQRVQLAAASAEREAAAREDNIRRVLEGFKEEPWDGFRAELERRARTIVVS HRPEHGIGGALHKETAYGPVDPPEEGFNLVVRKPIDGLSKDEINSVRDPRLRRALIDRLAIRRR DANDPATALAKAAEDLAAQPASRGIRRVRVLKKESNPIRVEHGGNPSGPRSGGPFHKLLLAGEV HHVDVALRADGRRWVGHWVTLFEAHGGRGADGAAAPPRLGDGERFLMRLHKGDCLKLEHKGRVR VMQVVKLEPSSNSVVVVEPHQVKTDRSKHVKI SCDQLRARGARRVTVDPLGRVRVHAPGARVGI GGDAGRTAMEPAEDIS

SEQ ID NO: 376

MKRTSLRAYRLGVDLGANSLGWFVVWLDDHGQPEGLGPGGVRIFPDGRNPQSKQSNAAGRRLAR SARRRRDRYLQRRGKLMGLLVKHGLMPADEPARKRLECLDPYGLRAKALDEVLPLHHVGRALFH LNQRRGLFANRAIEQGDKDASAIKAAAGRLQTSMQACGARTLGEFLNRRHQLRATVRARSPVGG DVQARYEFYPTRAMVDAEFEAIWAAQAPHHPTMTAEAHDTIREAIFSQRAMKRPS IGKCSLDPA TSQDDVDGFRCAWSHPLAQRFRIWQDVRNLAVVETGPTSSRLGKEDQDKVARALLQTDQLSFDE IRGLLGLPSDARFNLESDRRDHLKGDATGAILSARRHFGPAWHDRSLDRQIDIVALLESALDEA AIIASLGTTHSLDEAAAQRALSALLPDGYCRLGLRAIKRVLPLMEAGRTYAEAASAAGYDHALL PGGKLSPTGYLPYYGQWLQNDVVGSDDERDTNERRWGRLPNPTVHIGIGQLRRVVNELIRWHGP PAEITVELTRDLKLSPRRLAELEREQAENQRKNDKRTSLLRKLGLPASTHNLLKLRLWDEQGDV ASECPYTGEAIGLERLVSDDVDIDHLIPFS I SWDDSAANKVVCMRYANREKGNRTPFEAFGHRQ GRPYDWADIAERAARLPRGKRWRFGPGARAQFEELGDFQARLLNETSWLARVAKQYLAAVTHPH RIHVLPGRLTALLRATWELNDLLPGSDDRAAKSRKDHRHHAIDALVAALTDQALLRRMANAHDD TRRKIEVLLPWPTFRIDLETRLKAMLVSHKPDHGLQARLHEDTAYGTVEHPETEDGANLVYRKT FVDI SEKEIDRIRDRRLRDLVRAHVAGERQQGKTLKAAVLSFAQRRDIAGHPNGIRHVRLTKS I KPDYLVPIRDKAGRIYKSYNAGENAFVDILQAESGRWIARATTVFQANQANESHDAPAAQPIMR VFKGDMLRIDHAGAEKFVKIVRLSPSNNLLYLVEHHQAGVFQTRHDDPEDSFRWLFASFDKLRE WNAELVRIDTLGQPWRRKRGLETGSEDATRIGWTRPKKWP

SEQ ID NO: 377

MERIFGFDIGTTS IGFSVIDYSSTQSAGNIQRLGVRIFPEARDPDGTPLNQQRRQKRMMRRQLR RRRIRRKALNETLHEAGFLPAYGSADWPVVMADEPYELRRRGLEEGLSAYEFGRAIYHLAQHRH FKGRELEESDTPDPDVDDEKEAANERAATLKALKNEQTTLGAWLARRPPSDRKRGIHAHRNVVA EEFERLWEVQSKFHPALKSEEMRARI SDTIFAQRPVFWRKNTLGECRFMPGEPLCPKGSWLSQQ RRMLEKLNNLAIAGGNARPLDAEERDAILSKLQQQASMSWPGVRSALKALYKQRGEPGAEKSLK FNLELGGESKLLGNALEAKLADMFGPDWPAHPRKQEIRHAVHERLWAADYGETPDKKRVI ILSE KDRKAHREAAANSFVADFGITGEQAAQLQALKLPTGWEPYS IPALNLFLAELEKGERFGALVNG PDWEGWRRTNFPHRNQPTGEILDKLPSPASKEERERI SQLRNPTVVRTQNELRKVVNNLIGLYG KPDRIRIEVGRDVGKSKREREEIQSGIRRNEKQRKKATEDLIKNGIANPSRDDVEKWILWKEGQ ERCPYTGDQIGFNALFREGRYEVEHIWPRSRSFDNSPRNKTLCRKDVNIEKGNRMPFEAFGHDE DRWSAIQIRLQGMVSAKGGTGMSPGKVKRFLAKTMPEDFAARQLNDTRYAAKQILAQLKRLWPD MGPEAPVKVEAVTGQVTAQLRKLWTLNNILADDGEKTRADHRHHAIDALTVACTHPGMTNKLSR YWQLRDDPRAEKPALTPPWDTIRADAEKAVSEIVVSHRVRKKVSGPLHKETTYGDTGTDIKTKS GTYRQFVTRKKIESLSKGELDEIRDPRIKEIVAAHVAGRGGDPKKAFPPYPCVSPGGPEIRKVR LTSKQQLNLMAQTGNGYADLGSNHHIAIYRLPDGKADFEIVSLFDASRRLAQRNPIVQRTRADG ASFVMSLAAGEAIMIPEGSKKGIWIVQGVWASGQVVLERDTDADHSTTTRPMPNPILKDDAKKV SIDPIGRVRPSND

SEQ ID NO: 378

MNKRILGLDTGTNSLGWAVVDWDEHAQSYELIKYGDVIFQEGVKIEKGIESSKAAERSGYKAIR KQYFRRRLRKIQVLKVLVKYHLCPYLSDDDLRQWHLQKQYPKSDELMLWQRTSDEEGKNPYYDR HRCLHEKLDLTVEADRYTLGRALYHLTQRRGFLSNRLDTSADNKEDGVVKSGI SQLSTEMEEAG CEYLGDYFYKLYDAQGNKVRIRQRYTDRNKHYQHEFDAICEKQELSSELIEDLQRAIFFQLPLK SQRHGVGRCTFERGKPRCADSHPDYEEFRMLCFVNNIQVKGPHDLELRPLTYEEREKIEPLFFR KSKPNFDFEDIAKALAGKKNYAWIHDKEERAYKFNYRMTQGVPGCPTIAQLKS IFGDDWKTGIA ETYTLIQKKNGSKSLQEMVDDVWNVLYSFSSVEKLKEFAHHKLQLDEESAEKFAKIKLSHSFAA LSLKAIRKFLPFLRKGMYYTHASFFANIPTIVGKEIWNKEQNRKYIMENVGELVFNYQPKHREV QGTIEMLIKDFLANNFELPAGATDKLYHPSMIETYPNAQRNEFGILQLGSPRTNAIRNPMAMRS LHILRRVVNQLLKES I IDENTEVHVEYARELNDANKRRAIADRQKEQDKQHKKYGDEIRKLYKE ETGKDIEPTQTDVLKFQLWEEQNHHCLYTGEQIGITDFIGSNPKFDIEHTIPQSVGGDSTQMNL TLCDNRFNREVKKAKLPTELANHEEILTRIEPWKNKYEQLVKERDKQRTFAGMDKAVKDIRIQK RHKLQMEIDYWRGKYERFTMTEVPEGFSRRQGTGIGLI SRYAGLYLKSLFHQADSRNKSNVYVV KGVATAEFRKMWGLQSEYEKKCRDNHSHHCMDAITIACIGKREYDLMAEYYRMEETFKQGRGSK PKFSKPWATFTEDVL IYKNLLVVHDTPNNMPKHTKKYVQTS IGKVLAQGDTARGSLHLDTYYG AIERDGEIRYVVRRPLSSFTKPEELENIVDETVKRTIKEAIADKNFKQAIAEPIYMNEEKGILI KKVRCFAKSVKQPINIRQHRDLSKKEYKQQYHVMNENNYLLAIYEGLVKNKVVREFEIVSYIEA AKYYKRSQDRNIFSS IVPTHSTKYGLPLKTKLLMGQLVLMFEENPDEIQVDNTKDLVKRLYKVV GIEKDGRIKFKYHQEARKEGLPIFSTPYKNNDDYAPIFRQS INNINILVDGIDFTIDILGKVTL KE

SEQ ID NO: 379

MNYKMGLDIGIASVGWAVINLDLKRIEDLGVRIFDKAEHPQNGESLALPRRIARSARRRLRRRK HRLERIRRLLVSENVLTKEEMNLLFKQKKQIDVWQLRVDALERKLNNDELARVLLHLAKRRGFK SNRKSERNSKESSEFLKNIEENQS ILAQYRSVGEMIVKDSKFAYHKRNKLDSYSNMIARDDLER EIKLIFEKQREFNNPVCTERLEEKYLNIWSSQRPFASKEDIEKKVGFCTFEPKEKRAPKATYTF QSFIVWEHINKLRLVSPDETRALTEIERNLLYKQAFSKNKMTYYDIRKLLNLSDDIHFKGLLYD PKSSLKQIENIRFLELDSYHKIRKCIENVYGKDGIRMFNETDIDTFGYALTIFKDDEDIVAYLQ NEYITKNGKRVSNLANKVYDKSLIDELLNLSFSKFAHLSMKAIR ILPYMEQGEIYSKACELAG YNFTGPKKKEKALLLPVIPNIANPVVMRALTQSRKVVNAI IKKYGSPVS IHIELARDLSHSFDE RKKIQKDQTENRKKNETAIKQLIEYELTKNPTGLDIVKFKLWSEQQGRCMYSLKPIELERLLEP GYVEVDHILPYSRSLDDSYANKVLVLTKENREKGNHTPVEYLGLGSERWKKFEKFVLANKQFSK KKKQNLLRLRYEETEEKEFKERNLNDTRYI SKFFANFIKEHLKFADGDGGQKVYTINGKITAHL RSRWDFNKNREESDLHHAVDAVIVACATQGMIKKITEFYKAREQNKESAKKKEPIFPQPWPHFA DELKARLSKFPQES IEAFALGNYDRKKLESLRPVFVSRMPKRSVTGAAHQETLRRCVGIDEQSG KIQTAVKTKLSDIKLDKDGHFPMYQKESDPRTYEAIRQRLLEHNNDPKKAFQEPLYKPKKNGEP GPVIRTVKI IDTKNKVVHLDGSKTVAYNS IVRTDVFEKDGKYYCVPVYTMDIMKGTLPNKAIE ANKPYSEWKEMTEEYTFQFSLFPNDLVRIVLPREKTIKTSTNEEI I IKDIFAYYKTIDSATGGL ELI SHDRNFSLRGVGSKTLKRFEKYQVDVLG IHKVKGEKRVGLAAPTNQKKGKTVDSLQSVSD

SEQ ID NO: 380

MRRLGLDLGTNS IGWCLLDLGDDGEPVS IFRTGARIFSDGRDPKSLGSLKATRREARLTRRRRD RFIQRQKNLINALVKYGLMPADEIQRQALAYKDPYPIRKKALDEAIDPYEMGRAIFHINQRRGF KSNRKSADNEAGVVKQS IADLEMKLGEAGARTIGEFLADRQATNDTVRARRLSGTNALYEFYPD RYMLEQEFDTLWAKQAAFNPSLYIEAARERLKEIVFFQRKLKPQEVGRCIFLSDEDRI SKALPS FQRFRIYQELSNLAWIDHDGVAHRITASLALRDHLFDELEHKKKLTFKAMRAILRKQGVVDYPV GFNLESDNRDHLIGNLTSCIMRDAKKMIGSAWDRLDEEEQDSFILMLQDDQKGDDEVRS ILTQQ YGLSDDVAEDCLDVRLPDGHGSLSKKAIDRILPVLRDQGLIYYDAVKEAGLGEANLYDPYAALS DKLDYYGKALAGHVMGASGKFEDSDEKRYGTI SNPTVHIALNQVRAVVNELIRLHGKPDEVVIE IGRDLPMGADGKRELERFQKEGRAKNERARDELKKLGHIDSRESRQKFQLWEQLAKEPVDRCCP FTGKMMS I SDLFSDKVEIEHLLPFSLTLDDSMANKTVCFRQANRDKGNRAPFDAFGNSPAGYDW QEILGRSQNLPYAKRWRFLPDAMKRFEADGGFLERQLNDTRYI SRYTTEYI STI IPKNKIWVVT GRLTSLLRGFWGLNS ILRGHNTDDGTPAKKSRDDHRHHAIDAIVVGMTSRGLLQKVSKAARRSE DLDLTRLFEGRIDPWDGFRDEVKKHIDAI IVSHRPRKKSQGALHNDTAYGIVEHAENGASTVVH RVPITSLGKQSDIEKVRDPLIKSALLNETAGLSGKSFENAVQKWCADNS IKSLRIVETVS I IPI TDKEGVAYKGYKGDGNAYMDIYQDPTSSKWKGEIVSRFDANQKGFIPSWQSQFPTARLIMRLRI NDLLKLQDGEIEEIYRVQRLSGSKILMAPHTEANVDARDRDKNDTFKLTSKSPGKLQSASARKV HISPTGLIREG SEQ ID NO: 381

MK ILGLDLGLSS IGWSVIRENSEEQELVAMGSRVVSLTAAELSSFTQGNGVS INSQRTQKRTQ RKGYDRYQLRRTLLRNKLDTLGMLPDDSLSYLPKLQLWGLRAKAVTQRIELNELGRVLLHLNQK RGYKS IKSDFSGDKKITDYVKTVKTRYDELKEMRLTIGELFFRRLTENAFFRCKEQVYPRQAYV EEFDCIMNCQRKFYPDILTDETIRCIRDEI IYYQRPLKSCKYLVSRCEFEKRFYLNAAGKKTEA GPKVSPRTSPLFQVCRLWES IN IVVKDRRNEIVFI SAEQRAALFDFLNTHEKLKGSDLLKLLG LSKTYGYRLGEQFKTGIQGNKTRVEIERALGNYPDKKRLLQFNLQEESSSMVNTETGEI IPMI S LSFEQEPLYRLWHVLYS IDDREQLQSVLRQKFGIDDDEVLERLSAIDLVKAGFGNKSSKAIRRI LPFLQLGMNYAEACEAAGYNHSNNYTKAENEARALLDRLPAIKKNELRQPVVEKILNQMVNVVN ALMEKYGRFDEIRVELARELKQSKEERSNTYKS INKNQRENEQIAKRIVEYGVPTRSRIQKYKM WEESKHCCIYCGQPVDVGDFLRGFDVEVEHI IPKSLYFDDSFANKVCSCRSCNKEKNNRTAYDY MKSKGEKALSDYVERVNTMYTNNQI SKTKWQNLLTPVDKI S IDFIDRQLRESQYIARKAKEILT SICYNVTATSGSVTSFLRHVWGWDTVLHDLNFDRYKKVGLTEVIEVNHRGSVIRREQIKDWSKR FDHRHHAIDALTIACTKQAYIQRLNNLRAEEGPDFNKMSLERYIQSQPHFSVAQVREAVDRILV SFRAGKRAVTPGKRYIRKNRKRI SVQSVLIPRGALSEESVYGVIHVWEKDEQGHVIQKQRAVMK YPITS INREMLDKEKVVDKRIHRILSGRLAQYNDNPKEAFAKPVYIDKECRIPIRTVRCFAKPA INTLVPLKKDDKGNPVAWVNPGNNHHVAIYRDEDGKYKERTVTFWEAVDRCRVGIPAIVTQPDT IWD ILQRNDI SENVLESLPDVKWQFVLSLQQNEMFILGMNEEDYRYAMDQQDYALLNKYLYRV QKLSKSDYSFRYHTETSVEDKYDGKPNLKLSMQMGKLKRVS IKSLLGLNPHKVHI SVLGEIKEI S

SEQ ID NO: 382

MAEKQHRWGLDIGTNS IGWAVIALIEGRPAGLVATGSRIFSDGRNPKDGSSLAVERRGPRQMRR RRDRYLRRRDRFMQALINVGLMPGDAAARKALVTENPYVLRQRGLDQALTLPEFGRALFHLNQR RGFQSNRKTDRATAKESGKVKNAIAAFRAGMGNARTVGEALARRLEDGRPVRARMVGQGKDEHY ELYIAREWIAQEFDALWASQQRFHAEVLADAARDRLRAILLFQRKLLPVPVGKCFLEPNQPRVA AALPSAQRFRLMQELNHLRVMTLADKRERPLSFQERNDLLAQLVARPKCGFDMLRKIVFGANKE AYRFTIESERRKELKGCDTAAKLAKVNALGTRWQALSLDEQDRLVCLLLDGENDAVLADALREH YGLTDAQIDTLLGLSFEDGHMRLGRSALLRVLDALESGRDEQGLPLSYDKAVVAAGYPAHTADL ENGERDALPYYGELLWRYTQDAPTAKNDAERKFGKIANPTVHIGLNQLRKLVNALIQRYGKPAQ IVVELARNLKAGLEEKERIKKQQTANLERNERIRQKLQDAGVPDNRENRLRMRLFEELGQGNGL GTPCIYSGRQI SLQRLFSNDVQVDHILPFSKTLDDSFANKVLAQHDANRYKGNRGPFEAFGANR DGYAWDDIRARAAVLPRNKRNRFAETAMQDWLHNETDFLARQLTDTAYLSRVARQYLTAICSKD DVYVSPGRLTAMLRAKWGLNRVLDGVMEEQGRPAVKNRDDHRHHAIDAVVIGATDRAMLQQVAT LAARAREQDAERLIGDMPTPWPNFLEDVRAAVARCVVSHKPDHGPEGGLHNDTAYGIVAGPFED GRYRVRHRVSLFDLKPGDLSNVRCDAPLQAELEPIFEQDDARAREVALTALAERYRQRKVWLEE LMSVLPIRPRGEDGKTLPDSAPYKAYKGDSNYCYELFINERGRWDGELI STFRANQAAYRRFRN DPARFRRYTAGGRPLLMRLCINDYIAVGTAAERTIFRVVKMSENKITLAEHFEGGTLKQRDADK DDPFKYLTKSPGALRDLGARRIFVDLIGRVLDPGIKGD

SEQ ID NO: 383

MIERILGVDLGI SSLGWAIVEYDKDDEAANRI IDCGVRLFTAAETPKKKESPNKARREARGIRR VLNRRRVRMNMIKKLFLRAGLIQDVDLDGEGGMFYSKANRADVWELRHDGLYRLLKGDELARVL IHIAKHRGYKFIGDDEADEESGKVKKAGVVLRQNFEAAGCRTVGEWLWRERGANGKKRNKHGDY EI S IHRDLLVEEVEAIFVAQQEMRSTIATDALKAAYREIAFFVRPMQRIEKMVGHCTYFPEERR APKSAPTAEKFIAI SKFFSTVI IDNEGWEQKI IERKTLEELLDFAVSREKVEFRHLRKFLDLSD NEIFKGLHYKGKPKTAKKREATLFDPNEPTELEFDKVEAEKKAWI SLRGAAKLREALGNEFYGR FVALGKHADEATKILTYYKDEGQKRRELTKLPLEAEMVERLVKIGFSDFLKLSLKAIRDILPAM ESGARYDEAVLMLGVPHKEKSAILPPLNKTDIDILNPTVIRAFAQFRKVANALVRKYGAFDRVH FELAREINTKGEIEDIKESQRKNEKERKEAADWIAETSFQVPLTRKNILKKRLYIQQDGRCAYT GDVIELERLFDEGYCEIDHILPRSRSADDSFANKVLCLARANQQKTDRTPYEWFGHDAARWNAF ETRTSAPSNRVRTGKGKIDRLLKKNFDENSEMAFKDRNLNDTRYMARAIKTYCEQYWVFKNSHT KAPVQVRSGKLTSVLRYQWGLESKDRESHTHHAVDAI I IAFSTQGMVQKLSEYYRFKETHREKE RPKLAVPLANFRDAVEEATRIENTETVKEGVEVKRLLI SRPPRARVTGQAHEQTAKPYPRIKQV KNKKKWRLAPIDEEKFESFKADRVASANQKNFYETSTIPRVDVYHKKGKFHLVPIYLHEMVLNE LPNLSLGTNPEAMDENFFKFS IFKDDLI S IQTQGTPKKPAKI IMGYFKNMHGANMVLSS INNSP CEGFTCTPVSMDKKHKDKCKLCPEENRIAGRCLQGFLDYWSQEGLRPPRKEFECDQGVKFALDV KKYQIDPLGYYYEVKQEKRLGTIPQMRSAKKLVKK

SEQ ID NO: 384

MNNS IKSKPEVTIGLDLGVGSVGWAIVDNET I IHHLGSRLFSQAKTAEDRRSFRGVRRLIRRR KYKLKRFVNLIWKYNSYFGFKNKEDILNNYQEQQKLHNTVLNLKSEALNAKIDPKALSWILHDY LKNRGHFYEDNRDFNVYPTKELAKYFDKYGYYKGI IDSKEDNDNKLEEELTKYKFSNKHWLEEV KKVLSNQTGLPEKFKEEYESLFSYVRNYSEGPGS INSVSPYGIYHLDEKEGKVVQKYN IWDKT IGKCNIFPDEYRAPKNSPIAMIFNEINELSTIRSYS IYLTGWFINQEFKKAYLNKLLDLLIKTN GEKPIDARQFKKLREETIAES IGKETLKDVENEEKLEKEDHKWKLKGLKLNTNGKIQYNDLSSL AKFVHKLKQHLKLDFLLEDQYATLDKINFLQSLFVYLGKHLRYSNRVDSANLKEFSDSNKLFER ILQKQKDGLFKLFEQTDKDDEKILAQTHSLSTKAMLLAITRMTNLDNDEDNQKNNDKGWNFEAI KNFDQKFIDITKKNNNLSLKQNKRYLDDRFINDAILSPGVKRILREATKVFNAILKQFSEEYDV TKVVIELARELSEEKELENTKNYKKLIKKNGDKI SEGLKALGI SEDEIKDILKSPTKSYKFLLW LQQDHIDPYSLKEIAFDDIFTKTEKFEIDHI IPYS I SFDDSSSNKLLVLAESNQAKSNQTPYEF ISSGNAGIKWEDYEAYCRKFKDGDSSLLDSTQRSKKFAKMMKTDTSSKYDIGFLARNLNDTRYA TIVFRDALEDYANNHLVEDKPMFKVVCINGSVTSFLRKNFDDSSYAKKDRDK IHHAVDAS IIS IFSNETKTLFNQLTQFADYKLFKNTDGSWKKIDPKTGVVTEVTDENWKQIRVRNQVSEIAKVIE KYIQDS IERKARYSRKIENKT I SLFNDTVYSAKKVGYEDQIKRKNLKTLDIHESAKENKNSK VKRQFVYRKLVNVSLLNNDKLADLFAEKEDILMYRANPWVINLAEQIFNEYTENKKIKSQNVFE KYMLDLTKEFPEKFSEFLVKSMLRNKTAI IYDDKK IVHRIKRLKMLSSELKENKLSNVI IRSK NQSGTKLSYQDTINSLALMIMRS IDPTAKKQYIRVPLNTLNLHLGDHDFDLHNMDAYLKKPKFV KYLKANEIGDEYKPWRVLTSGTLLIHKKDKKLMYISSFQNLNDVIEIKNLIETEYKENDDSDSK KKKKANRFLMTLSTILNDYILLDAKDNFDILGLSKNRIDEILNSKLGLDKIVK

SEQ ID NO: 385

MGGSEVGTVPVTWRLGVDVGERS IGLAAVSYEEDKPKEILAAVSWIHDGGVGDERSGASRLALR GMARRARRLRRFRRARLRDLDMLLSELGWTPLPDKNVSPVDAWLARKRLAEEYVVDETERRRLL GYAVSHMARHRGWRNPWTTIKDLKNLPQPSDSWERTRESLEARYSVSLEPGTVGQWAGYLLQRA PGIRLNPTQQSAGRRAELSNATAFETRLRQEDVLWELRCIADVQGLPEDVVSNVIDAVFCQKRP SVPAERIGRDPLDPSQLRASRACLEFQEYRIVAAVANLRIRDGSGSRPLSLEERNAVIEALLAQ TERSLTWSDIALEILKLPNESDLTSVPEEDGPSSLAYSQFAPFDETSARIAEFIAKNRRKIPTF AQWWQEQDRTSRSDLVAALADNS IAGEEEQELLVHLPDAELEALEGLALPSGRVAYSRLTLSGL TRVMRDDGVDVHNARKTCFGVDDNWRPPLPALHEATGHPVVDRNLAILRKFLSSATMRWGPPQS IVVELARGASESRERQAEEEAARRAHRKANDRIRAELRASGLSDPSPADLVRARLLELYDCHCM YCGAPI SWENSELDHIVPRTDGGSNRHENLAITCGACNKEKGRRPFASWAETSNRVQLRDVIDR VQKLKYSGNMYWTRDEFSRYKKSVVARLKRRTSDPEVIQS IESTGYAAVALRDRLLSYGEKNGV AQVAVFRGGVTAEARRWLDI S IERLFSRVAIFAQSTSTKRLDRRHHAVDAVVLTTLTPGVAKTL ADARSRRVSAEFWRRPSDVNRHSTEEPQSPAYRQWKESCSGLGDLLI STAARDS IAVAAPLRLR PTGALHEETLRAFSEHTVGAAWKGAELRRIVEPEVYAAFLALTDPGGRFLKVSPSEDVLPADEN RHIVLSDRVLGPRDRVKLFPDDRGS IRVRGGAAYIASFHHARVFRWGSSHSPSFALLRVSLADL AVAGLLRDGVDVFTAELPPWTPAWRYAS IALVKAVESGDAKQVGWLVPGDELDFGPEGVTTAAG DLSMFLKYFPERHWVVTGFEDDKRINLKPAFLSAEQAEVLRTERSDRPDTLTEAGEILAQFFPR CWRATVAKVLCHPGLTVIRRTALGQPRWRRGHLPYSWRPWSADPWSGGTP

SEQ ID NO: 386

MHNKKNITIGFDLGIAS IGWAI IDSTTSKILDWGTRTFEERKTANERRAFRSTRRNIRRKAYRN QRFINLILKYKDLFELKNI SDIQRANKKDTENYEKI I SFFTEIYKKCAAKHSNILEVKVKALDS KIEKLDLIWILHDYLENRGFFYDLEEENVADKYEGIEHPS ILLYDFFKKNGFFKSNSS IPKDLG GYSFSNLQWVNEIKKLFEVQEINPEFSEKFLNLFTSVRDYAKGPGSEHSASEYGIFQKDEKGKV FKKYDNIWDKTIGKCSFFVEENRSPVNYPSYEIFNLLNQLINLSTDLKTTNKKIWQLSSNDRNE LLDELLKVKEKAKI I S I SLKKNEIKKI ILKDFGFEKSDIDDQDTIEGRKI IKEEPTTKLEVTKH LLATIYSHSSDSNWININNILEFLPYLDAICI ILDREKSRGQDEVLKKLTEKNIFEVLKIDREK QLDFVKS IFSNTKFNFKKIGNFSLKAIREFLPKMFEQNKNSEYLKWKDEEIRRKWEEQKSKLGK TDKKTKYLNPRIFQDEI I SPGTKNTFEQAVLVLNQI IKKYSKENI IDAI I IESPREKNDKKTIE EIKKRNKKGKGKTLEKLFQILNLENKGYKLSDLETKPAKLLDRLRFYHQQDGIDLYTLDKINID QLINGSQKYEIEHI IPYSMSYDNSQANKILTEKAENLKKGKLIASEYIKRNGDEFYNKYYEKAK ELFINKYKKNKKLDSYVDLDEDSAKNRFRFLTLQDYDEFQVEFLARNLNDTRYSTKLFYHALVE HFENNEFFTYIDENSSKHKVKI STIKGHVTKYFRAKPVQKNNGPNENLNNNKPEKIEKNRENNE HHAVDAAIVAI IGNKNPQIANLLTLADNKTDKKFLLHDENYKENIETGELVKIPKFEVDKLAKV EDLKKI IQEKYEEAKKHTAIKFSRKTRTILNGGLSDETLYGFKYDEKEDKYFKI IKKKLVTSKN EELKKYFENPFGKKADGKSEYTVLMAQSHLSEFNKLKEIFEKYNGFSNKTGNAFVEYMNDLALK EPTLKAEIESAKSVEKLLYYNFKPSDQFTYHDNINNKSFKRFYKNIRI IEYKS IPIKFKILSKH DGGKSFKDTLFSLYSLVYKVYENGKESYKS IPVTSQMRNFGIDEFDFLDENLYNKEKLDIYKSD FAKPIPVNCKPVFVLKKGS ILKKKSLDIDDFKETKETEEGNYYFI STI SKRFNRDTAYGLKPLK LSVVKPVAEPSTNPIFKEYIPIHLDELGNEYPVKIKEHTDDEKLMCTIK

Nucleic Acids Encoding Cas9 Molecules

Nucleic acids encoding the Cas9 molecules or Cas9 polypeptides, e.g., an eaCas9 molecule or eaCas9 polypeptide are provided herein.

Exemplary nucleic acids encoding Cas9 molecules are described in Cong et ah, SCIENCE 2013, 399(6121):819-823; Wang et al, CELL 2013, 153(4):910-918; Mali et al, SCIENCE 2013, 399(6121):823-826; Jinek et al, SCIENCE 2012, 337(6096):816-821. Another exemplary nucleic acid encoding a Cas9 molecule or Cas9 polypeptide is shown in Fig. 8.

In an embodiment, a nucleic acid encoding a Cas9 molecule or Cas9 polypeptide can be a synthetic nucleic acid sequence. For example, the synthetic nucleic acid molecule can be chemically modified, e.g., as described in Section VIII. In an embodiment, the Cas9 mRNA has one or more (e.g., all of the following properties: it is capped, polyadenylated, substituted with 5- methylcytidine and/or pseudouridine. In addition, or alternatively, the synthetic nucleic acid sequence can be codon optimized, e.g., at least one non-common codon or less-common codon has been replaced by a common codon. For example, the synthetic nucleic acid can direct the synthesis of an optimized messenger mRNA, e.g., optimized for expression in a mammalian expression system, e.g., described herein.

In addition, or alternatively, a nucleic acid encoding a Cas9 molecule or Cas9 polypeptide may comprise a nuclear localization sequence (NLS). Nuclear localization sequences are known in the art.

Provided below is an exemplary codon optimized nucleic acid sequence encoding a Cas9 molecule of S. pyogenes.

ATGGATAAAA AGTACAGCAT CGGGCTGGAC ATCGGTACAA ACTCAGTGGG GTGGGCCGTG ATTACGGACG AGTACAAGGT ACCCTCCAAA AAATTTAAAG TGCTGGGTAA CACGGACAGA CACTCTATAA AGAAAAATCT TATTGGAGCC TTGCTGTTCG ACTCAGGCGA GACAGCCGAA GCCACAAGGT TGAAGCGGAC CGCCAGGAGG CGGTATACCA GGAGAAAGAA CCGCATATGC TACCTGCAAG AAATCTTCAG TAACGAGATG GCAAAGGTTG ACGATAGCTT TTTCCATCGC CTGGAAGAAT CCTTTCTTGT TGAGGAAGAC AAGAAGCACG AACGGCACCC CATCTTTGGC AATATTGTCG ACGAAGTGGC ATATCACGAA AAGTACCCGA CTATCTACCA CCTCAGGAAG AAGCTGGTGG ACTCTACCGA TAAGGCGGAC CTCAGACTTA TTTATTTGGC ACTCGCCCAC AT GAT T AAA T TTAGAGGACA TTTCTTGATC GAGGGCGACC TGAACCCGGA CAACAGTGAC GTCGATAAGC TGTTCATCCA ACTTGTGCAG ACCTACAATC AACTGTTCGA AGAAAACCCT ATAAATGCTT CAGGAGTCGA CGCTAAAGCA ATCCTGTCCG CGCGCCTCTC AAAATCTAGA AGACTTGAGA ATCTGATTGC TCAGTTGCCC GGGGAAAAGA AAAATGGATT GTTTGGCAAC CTGATCGCCC TCAGTCTCGG ACTGACCCCA AATTTCAAAA GTAACTTCGA CCTGGCCGAA GACGCTAAGC TCCAGCTGTC CAAGGACACA TACGATGACG ACCTCGACAA TCTGCTGGCC CAGATTGGGG ATCAGTACGC CGATCTCTTT TTGGCAGCAA AGAACCTGTC CGACGCCATC CTGTTGAGCG ATATCTTGAG AGTGAACACC GAAATTACTA AAGCACCCCT TAGCGCATCT ATGATCAAGC GGTACGACGA GCATCATCAG GATCTGACCC TGCTGAAGGC TCTTGTGAGG CAACAGCTCC CCGAAAAATA CAAGGAAATC TTCTTTGACC AGAGCAAAAA CGGCTACGCT GGCTATATAG ATGGTGGGGC CAGTCAGGAG GAATTCTATA AATTCATCAA GCCCATTCTC GAGAAAATGG ACGGCACAGA GGAGTTGCTG GTCAAACTTA ACAGGGAGGA CCTGCTGCGG AAGCAGCGGA CCTTTGACAA CGGGTCTATC CCCCACCAGA TTCATCTGGG CGAACTGCAC GCAATCCTGA GGAGGCAGGA GGATTTTTAT CCTTTTCTTA AAGATAACCG CGAGAAAATA GAAAAGATTC TTACATTCAG GATCCCGTAC TACGTGGGAC CTCTCGCCCG GGGCAATTCA CGGTTTGCCT GGATGACAAG GAAGTCAGAG GAGACTATTA CACCTTGGAA CTTCGAAGAA GTGGTGGACA AGGGTGCATC TGCCCAGTCT TTCATCGAGC GGATGACAAA TTTTGACAAG AACCTCCCTA ATGAGAAGGT GCTGCCCAAA CATTCTCTGC TCTACGAGTA CTTTACCGTC TACAATGAAC TGACTAAAGT CAAGTACGTC ACCGAGGGAA TGAGGAAGCC GGCATTCCTT AGTGGAGAAC AGAAGAAGGC GATTGTAGAC CTGTTGTTCA AGACCAACAG GAAGGTGACT GTGAAGCAAC TTAAAGAAGA CTACTTTAAG AAGATCGAAT GTTTTGACAG TGTGGAAATT TCAGGGGTTG AAGACCGCTT CAATGCGTCA TTGGGGACTT ACCATGATCT TCTCAAGATC ATAAAGGACA AAGACTTCCT GGACAACGAA GAAAATGAGG ATATTCTCGA AGACATCGTC CTCACCCTGA CCCTGTTCGA AGACAGGGAA ATGATAGAAG AGCGCTTGAA AACCTATGCC CACCTCTTCG ACGATAAAGT TATGAAGCAG CTGAAGCGCA GGAGATACAC AGGATGGGGA AGATTGTCAA GGAAGCTGAT CAATGGAATT AGGGATAAAC AGAGTGGCAA GACCATACTG GATTTCCTCA AATCTGATGG CTTCGCCAAT AGGAACTTCA TGCAACTGAT TCACGATGAC TCTCTTACCT TCAAGGAGGA CATTCAAAAG GCTCAGGTGA GCGGGCAGGG AGACTCCCTT CATGAACACA TCGCGAATTT GGCAGGTTCC CCCGCTATTA AAAAGGGCAT CCTTCAAACT GTCAAGGTGG TGGATGAATT GGTCAAGGTA ATGGGCAGAC ATAAGCCAGA AAATATTGTG ATCGAGATGG CCCGCGAAAA CCAGACCACA CAGAAGGGCC AGAAAAATAG TAGAGAGCGG ATGAAGAGGA TCGAGGAGGG CATCAAAGAG CTGGGATCTC AGATTCTCAA AGAACACCCC GTAGAAAACA CACAGCTGCA GAACGAAAAA TTGTACTTGT ACTATCTGCA GAACGGCAGA GACATGTACG TCGACCAAGA ACTTGATATT AATAGACTGT CCGACTATGA CGTAGACCAT ATCGTGCCCC AGTCCTTCCT GAAGGACGAC TCCATTGATA ACAAAGTCTT GACAAGAAGC GACAAGAACA GGGGTAAAAG TGATAATGTG CCTAGCGAGG AGGTGGTGAA AAAAATGAAG AACTACTGGC GACAGCTGCT TAATGCAAAG CTCATTACAC AACGGAAGTT CGATAATCTG ACGAAAGCAG AGAGAGGTGG CTTGTCTGAG TTGGACAAGG CAGGGTTTAT TAAGCGGCAG CTGGTGGAAA CTAGGCAGAT CACAAAGCAC GTGGCGCAGA TTTTGGACAG CCGGATGAAC ACAAAATACG ACGAAAATGA TAAACTGATA CGAGAGGTCA AAGTTATCAC GCTGAAAAGC AAGCTGGTGT CCGATTTTCG GAAAGACTTC CAGTTCTACA AAGTTCGCGA GATTAATAAC TACCATCATG CTCACGATGC GTACCTGAAC GCTGTTGTCG GGACCGCCTT GATAAAGAAG TACCCAAAGC TGGAATCCGA GTTCGTATAC GGGGATTACA AAGTGTACGA TGTGAGGAAA ATGATAGCCA AGTCCGAGCA GGAGATTGGA AAGGCCACAG CTAAGTACTT CTTTTATTCT AACATCATGA ATTTTTTTAA GACGGAAATT ACCCTGGCCA ACGGAGAGAT CAGAAAGCGG CCCCTTATAG AGACAAATGG TGAAACAGGT GAAATCGTCT GGGATAAGGG CAGGGATTTC GCTACTGTGA GGAAGGTGCT GAGTATGCCA CAGGTAAATA TCGTGAAAAA AACCGAAGTA CAGACCGGAG GATTTTCCAA GGAAAGCATT TTGCCTAAAA GAAACTCAGA CAAGCTCATC GCCCGCAAGA AAGATTGGGA CCCTAAGAAA TACGGGGGAT TTGACTCACC CACCGTAGCC TATTCTGTGC TGGTGGTAGC TAAGGTGGAA AAAGGAAAGT CTAAGAAGCT GAAGTCCGTG AAGGAACTCT TGGGAATCAC TATCATGGAA AGATCATCCT TTGAAAAGAA CCCTATCGAT TTCCTGGAGG CTAAGGGTTA CAAGGAGGTC AAGAAAGACC TCATCATTAA ACTGCCAAAA TACTCTCTCT TCGAGCTGGA AAATGGCAGG AAGAGAATGT TGGCCAGCGC CGGAGAGCTG CAAAAGGGAA ACGAGCTTGC TCTGCCCTCC AAATATGTTA ATTTTCTCTA TCTCGCTTCC CACTATGAAA AGCTGAAAGG GTCTCCCGAA GATAACGAGC AGAAGCAGCT GTTCGTCGAA CAGCACAAGC ACTATCTGGA TGAAATAATC GAACAAATAA GCGAGTTCAG CAAAAGGGTT ATCCTGGCGG ATGCTAATTT GGACAAAGTA CTGTCTGCTT ATAACAAGCA CCGGGATAAG CCTATTAGGG AACAAGCCGA GAATATAATT CACCTCTTTA CACTCACGAA TCTCGGAGCC CCCGCCGCCT TCAAATACTT TGATACGACT ATCGACCGGA

AACGGTATAC CAGTACCAAA GAGGTCCTCG ATGCCACCCT CATCCACCAG TCAATTACTG GCCTGTACGA AACACGGATC GACCTCTCTC AACTGGGCGG CGACTAG

(SEQ ID NO: 22)

Provided below is the corresponding amino acid sequence of a S. pyogenes Cas9 molecule.

MDKKYS IGLDIGTNSVGWAVITDEYKVPSKKFKVLGNTDRHS IKKNLIGALLFDSGETAEATRL KRTARRRYTRRKNRICYLQEIFSNEMAKVDDSFFHRLEESFLVEEDKKHERHPIFGNIVDEVAY HEKYPTIYHLRKKLVDSTDKADLRLIYLALAHMIKFRGHFLIEGDLNPDNSDVDKLFIQLVQTY NQLFEENPINASGVDAKAILSARLSKSRRLENLIAQLPGEKKNGLFGNLIALSLGLTPNFKSNF DLAEDAKLQLSKDTYDDDLDNLLAQIGDQYADLFLAAKNLSDAILLSDILRVNTEITKAPLSAS MIKRYDEHHQDLTLLKALVRQQLPEKYKEIFFDQSKNGYAGYIDGGASQEEFYKFIKPILEKMD GTEELLVKLNREDLLRKQRTFDNGS IPHQIHLGELHAILRRQEDFYPFLKDNREKIEKILTFRI PYYVGPLARGNSRFAWMTRKSEETITPWNFEEVVDKGASAQSFIERMTNFDKNLPNEKVLPKHS LLYEYFTVYNELTKVKYVTEGMRKPAFLSGEQKKAIVDLLFKTNRKVTVKQLKEDYFKKIECFD SVEI SGVEDRFNASLGTYHDLLKI IKDKDFLDNEENEDILEDIVLTLTLFEDREMIEERLKTYA HLFDDKVMKQLKRRRYTGWGRLSRKLINGIRDKQSGKTILDFLKSDGFANRNFMQLIHDDSLTF KEDIQKAQVSGQGDSLHEHIANLAGSPAIKKGILQTVKVVDELVKVMGRHKPENIVIEMARENQ TTQKGQKNSRERMKRIEEGIKELGSQILKEHPVENTQLQNEKLYLYYLQNGRDMYVDQELDINR LSDYDVDHIVPQSFLKDDS IDNKVLTRSDKNRGKSDNVPSEEVVKKMKNYWRQLLNAKLITQRK FDNLTKAERGGLSELDKAGFIKRQLVETRQITKHVAQILDSRMNTKYDENDKLIREVKVITLKS KLVSDFRKDFQFYKVREINNYHHAHDAYLNAVVGTALIKKYPKLESEFVYGDYKVYDVRKMIAK SEQEIGKATAKYFFYSNIMNFFKTEITLANGEIRKRPLIETNGETGEIVWDKGRDFATVRKVLS MPQV IVKKTEVQTGGFSKES ILPKRNSDKLIARKKDWDPKKYGGFDSPTVAYSVLVVAKVEKG KSKKLKSVKELLGITIMERSSFEKNPIDFLEAKGYKEVKKDLI IKLPKYSLFELENGRKRMLAS AGELQKGNELALPSKYVNFLYLASHYEKLKGSPEDNEQKQLFVEQHKHYLDEI IEQI SEFSKRV ILADANLDKVLSAYNKHRDKPIREQAE I IHLFTLTNLGAPAAFKYFDTTIDRKRYTSTKEVLD ATLIHQS ITGLYETRIDLSQLGGD*

(SEQ ID NO: 23)

Provided below is an exemplary codon optimized nucleic acid sequence encoding a Cas9 molecule of N. meningitidis.

ATGGCCGCCTTCAAGCCCAACCCCATCAACTACATCCTGGGCCTGGACATCGGCATCGCCAGCG TGGGCTGGGCCATGGTGGAGATCGACGAGGACGAGAACCCCATCTGCCTGATCGACCTGGGTGT GCGCGTGTTCGAGCGCGCTGAGGTGCCCAAGACTGGTGACAGTCTGGCTATGGCTCGCCGGCTT GCTCGCTCTGTTCGGCGCCTTACTCGCCGGCGCGCTCACCGCCTTCTGCGCGCTCGCCGCCTGC TGAAGCGCGAGGGTGTGCTGCAGGCTGCCGACTTCGACGAGAACGGCCTGATCAAGAGCCTGCC CAACACTCCTTGGCAGCTGCGCGCTGCCGCTCTGGACCGCAAGCTGACTCCTCTGGAGTGGAGC GCCGTGCTGCTGCACCTGATCAAGCACCGCGGCTACCTGAGCCAGCGCAAGAACGAGGGCGAGA CCGCCGACAAGGAGCTGGGTGCTCTGCTGAAGGGCGTGGCCGACAACGCCCACGCCCTGCAGAC TGGTGACTTCCGCACTCCTGCTGAGCTGGCCCTGAACAAGTTCGAGAAGGAGAGCGGCCACATC CGCAACCAGCGCGGCGACTACAGCCACACCTTCAGCCGCAAGGACCTGCAGGCCGAGCTGATCC TGCTGTTCGAGAAGCAGAAGGAGTTCGGCAACCCCCACGTGAGCGGCGGCCTGAAGGAGGGCAT CGAGACCCTGCTGATGACCCAGCGCCCCGCCCTGAGCGGCGACGCCGTGCAGAAGATGCTGGGC

CACTGCACCTTCGAGCCAGCCGAGCCCAAGGCCGCCAAGAACACCTACACCGCCGAGCGCTTCA

TCTGGCTGACCAAGCTGAACAACCTGCGCATCCTGGAGCAGGGCAGCGAGCGCCCCCTGACCGA

CACCGAGCGCGCCACCCTGATGGACGAGCCCTACCGCAAGAGCAAGCTGACCTACGCCCAGGCC

CGCAAGCTGCTGGGTCTGGAGGACACCGCCTTCTTCAAGGGCCTGCGCTACGGCAAGGACAACG

CCGAGGCCAGCACCCTGATGGAGATGAAGGCCTACCACGCCATCAGCCGCGCCCTGGAGAAGGA

GGGCCTGAAGGACAAGAAGAGTCCTCTGAACCTGAGCCCCGAGCTGCAGGACGAGATCGGCACC

GCCTTCAGCCTGTTCAAGACCGACGAGGACATCACCGGCCGCCTGAAGGACCGCATCCAGCCCG

AGATCCTGGAGGCCCTGCTGAAGCACATCAGCTTCGACAAGTTCGTGCAGATCAGCCTGAAGGC

CCTGCGCCGCATCGTGCCCCTGATGGAGCAGGGCAAGCGCTACGACGAGGCCTGCGCCGAGATC

TACGGCGACCACTACGGCAAGAAGAACACCGAGGAGAAGATCTACCTGCCTCCTATCCCCGCCG

ACGAGATCCGCAACCCCGTGGTGCTGCGCGCCCTGAGCCAGGCCCGCAAGGTGATCAACGGCGT

GGTGCGCCGCTACGGCAGCCCCGCCCGCATCCACATCGAGACCGCCCGCGAGGTGGGCAAGAGC

TTCAAGGACCGCAAGGAGATCGAGAAGCGCCAGGAGGAGAACCGCAAGGACCGCGAGAAGGCCG

CCGCCAAGTTCCGCGAGTACTTCCCCAACTTCGTGGGCGAGCCCAAGAGCAAGGACATCCTGAA

GCTGCGCCTGTACGAGCAGCAGCACGGCAAGTGCCTGTACAGCGGCAAGGAGATCAACCTGGGC

CGCCTGAACGAGAAGGGCTACGTGGAGATCGACCACGCCCTGCCCTTCAGCCGCACCTGGGACG

ACAGCTTCAACAACAAGGTGCTGGTGCTGGGCAGCGAGAACCAGAACAAGGGCAACCAGACCCC

CTACGAGTACTTCAACGGCAAGGACAACAGCCGCGAGTGGCAGGAGTTCAAGGCCCGCGTGGAG

ACCAGCCGCTTCCCCCGCAGCAAGAAGCAGCGCATCCTGCTGCAGAAGTTCGACGAGGACGGCT

TCAAGGAGCGCAACCTGAACGACACCCGCTACGTGAACCGCTTCCTGTGCCAGTTCGTGGCCGA

CCGCATGCGCCTGACCGGCAAGGGCAAGAAGCGCGTGTTCGCCAGCAACGGCCAGATCACCAAC

CTGCTGCGCGGCTTCTGGGGCCTGCGCAAGGTGCGCGCCGAGAACGACCGCCACCACGCCCTGG

ACGCCGTGGTGGTGGCCTGCAGCACCGTGGCCATGCAGCAGAAGATCACCCGCTTCGTGCGCTA

CAAGGAGATGAACGCCTTCGACGGTAAAACCATCGACAAGGAGACCGGCGAGGTGCTGCACCAG

AAGACCCACTTCCCCCAGCCCTGGGAGTTCTTCGCCCAGGAGGTGATGATCCGCGTGTTCGGCA

AGCCCGACGGCAAGCCCGAGTTCGAGGAGGCCGACACCCCCGAGAAGCTGCGCACCCTGCTGGC

CGAGAAGCTGAGCAGCCGCCCTGAGGCCGTGCACGAGTACGTGACTCCTCTGTTCGTGAGCCGC

GCCCCCAACCGCAAGATGAGCGGTCAGGGTCACATGGAGACCGTGAAGAGCGCCAAGCGCCTGG

ACGAGGGCGTGAGCGTGCTGCGCGTGCCCCTGACCCAGCTGAAGCTGAAGGACCTGGAGAAGAT

GGTGAACCGCGAGCGCGAGCCCAAGCTGTACGAGGCCCTGAAGGCCCGCCTGGAGGCCCACAAG

GACGACCCCGCCAAGGCCTTCGCCGAGCCCTTCTACAAGTACGACAAGGCCGGCAACCGCACCC

AGCAGGTGAAGGCCGTGCGCGTGGAGCAGGTGCAGAAGACCGGCGTGTGGGTGCGCAACCACAA

CGGCATCGCCGACAACGCCACCATGGTGCGCGTGGACGTGTTCGAGAAGGGCGACAAGTACTAC

CTGGTGCCCATCTACAGCTGGCAGGTGGCCAAGGGCATCCTGCCCGACCGCGCCGTGGTGCAGG

GCAAGGACGAGGAGGACTGGCAGCTGATCGACGACAGCTTCAACTTCAAGTTCAGCCTGCACCC

CAACGACCTGGTGGAGGTGATCACCAAGAAGGCCCGCATGTTCGGCTACTTCGCCAGCTGCCAC

CGCGGCACCGGCAACATCAACATCCGCATCCACGACCTGGACCACAAGATCGGCAAGAACGGCA

TCCTGGAGGGCATCGGCGTGAAGACCGCCCTGAGCTTCCAGAAGTACCAGATCGACGAGCTGGG

CAAGGAGATCCGCCCCTGCCGCCTGAAGAAGCGCCCTCCTGTGCGCTAA

(SEQ ID NO: 24)

Provided below is the corresponding amino acid sequence of a N. meningitidis Cas9 molecule.

MAAFKPNPINYILGLDIGIASVGWAMVEIDEDENPICLIDLGVRVFERAEVPKTGDSLAMARRL ARSVRRLTRRRAHRLLRARRLLKREGVLQAADFDENGLIKSLPNTPWQLRAAALDRKLTPLEWS AVLLHLIKHRGYLSQRKNEGETADKELGALLKGVADNAHALQTGDFRTPAELALNKFEKESGHI RNQRGDYSHTFSRKDLQAELILLFEKQKEFGNPHVSGGLKEGIETLLMTQRPALSGDAVQKMLG HCTFEPAEPKAAKNTYTAERFIWLTKLNNLRILEQGSERPLTDTERATLMDEPYRKSKLTYAQA RKLLGLEDTAFFKGLRYGKDNAEASTLMEMKAYHAI SRALEKEGLKDKKSPLNLSPELQDEIGT AFSLFKTDEDITGRLKDRIQPEILEALLKHI SFDKFVQI SLKALRRIVPLMEQGKRYDEACAEI YGDHYGKKNTEEKIYLPPIPADEIRNPVVLRALSQARKVINGVVRRYGSPARIHIETAREVGKS FKDRKEIEKRQEENRKDREKAAAKFREYFPNFVGEPKSKDILKLRLYEQQHGKCLYSGKEINLG RLNEKGYVEIDHALPFSRTWDDSFNNKVLVLGSENQNKGNQTPYEYFNGKDNSREWQEFKARVE TSRFPRSKKQRILLQKFDEDGFKERNLNDTRYVNRFLCQFVADRMRLTGKGKKRVFASNGQITN LLRGFWGLRKVRAENDRHHALDAVVVACSTVAMQQKITRFVRYKEMNAFDGKTIDKETGEVLHQ KTHFPQPWEFFAQEVMIRVFGKPDGKPEFEEADTPEKLRTLLAEKLSSRPEAVHEYVTPLFVSR APNRKMSGQGHMETVKSAKRLDEGVSVLRVPLTQLKLKDLEKMVNREREPKLYEALKARLEAHK DDPAKAFAEPFYKYDKAGNRTQQVKAVRVEQVQKTGVWVRNHNGIADNATMVRVDVFEKGDKYY LVPIYSWQVAKGILPDRAVVQGKDEEDWQLIDDSFNFKFSLHPNDLVEVITKKARMFGYFASCH RGTGNINIRIHDLDHKIGKNGILEGIGVKTALSFQKYQIDELGKEIRPCRLKKRPPVR* (SEQ ID NO: 25)

Provided below is an amino acid sequence of a S. aureus Cas9 molecule.

MKRNYILGLDIGITSVGYGI IDYETRDVIDAGVRLFKEANVENNEGRRSKRGARRLKRRRRHRI QRVKKLLFDYNLLTDHSELSGINPYEARVKGLSQKLSEEEFSAALLHLAKRRGVHNVNEVEEDT GNELSTKEQI SRNSKALEEKYVAELQLERLKKDGEVRGS INRFKTSDYVKEAKQLLKVQKAYHQ LDQSFIDTYIDLLETRRTYYEGPGEGSPFGWKDIKEWYEMLMGHCTYFPEELRSVKYAYNADLY NALNDLNNLVITRDENEKLEYYEKFQI IENVFKQKKKPTLKQIAKEILVNEEDIKGYRVTSTGK PEFTNLKVYHDIKDITARKEI IENAELLDQIAKILTIYQSSEDIQEELTNLNSELTQEEIEQIS NLKGYTGTHNLSLKAINLILDELWHTNDNQIAIFNRLKLVPKKVDLSQQKEIPTTLVDDFILSP VVKRSFIQS IKVINAI IKKYGLPNDI I IELAREKNSKDAQKMINEMQKRNRQTNERIEEI IRTT GKENAKYLIEKIKLHDMQEGKCLYSLEAIPLEDLLNNPFNYEVDHI IPRSVSFDNSFNNKVLVK QEENSKKGNRTPFQYLSSSDSKI SYETFKKHILNLAKGKGRI SKTKKEYLLEERDINRFSVQKD FINRNLVDTRYATRGLMNLLRSYFRVNNLDVKVKS INGGFTSFLRRKWKFKKERNKGYKHHAED ALI IA ADFIFKEWKKLDKAKKVMENQMFEEKQAESMPEIETEQEYKEIFITPHQIKHIKDFKD YKYSHRVDKKPNRELINDTLYSTRKDDKGNTLIVNNLNGLYDKDNDKLKKLINKSPEKLLMYHH DPQTYQKLKLIMEQYGDEKNPLYKYYEETGNYLTKYSKKDNGPVIKKIKYYGNKLNAHLDITDD YPNSRNKVVKLSLKPYRFDVYLDNGVYKFVTVKNLDVIKKENYYEVNSKCYEEAKKLKKISNQA EFIASFYNNDLIKINGELYRVIGVNNDLLNRIEVNMIDITYREYLENMNDKRPPRI IKTIASKT QS IKKYSTDILGNLYEVKSKKHPQI IKKG*

(SEQ ID NO: 26)

Provided below is an exemplary codon optimized nucleic acid sequence encoding a Cas9 molecule of S. aureus Cas9.

ATGAAAAGGAACTACATTCTGGGGCTGGACATCGGGATTACAAGCGTGGGGTATGGGATTATTG ACTATGAAACAAGGGACGTGATCGACGCAGGCGTCAGACTGTTCAAGGAGGCCAACGTGGAAAA CAATGAGGGACGGAGAAGCAAGAGGGGAGCCAGGCGCCTGAAACGACGGAGAAGGCACAGAATC CAGAGGGTGAAGAAACTGCTGTTCGATTACAACCTGCTGACCGACCATTCTGAGCTGAGTGGAA TTAATCCTTATGAAGCCAGGGTGAAAGGCCTGAGTCAGAAGCTGTCAGAGGAAGAGTTTTCCGC AGCTCTGCTGCACCTGGCTAAGCGCCGAGGAGTGCATAACGTCAATGAGGTGGAAGAGGACACC GGCAACGAGCTGTCTACAAAGGAACAGATCTCACGCAATAGCAAAGCTCTGGAAGAGAAGTATG TCGCAGAGCTGCAGCTGGAACGGCTGAAGAAAGATGGCGAGGTGAGAGGGTCAATTAATAGGTT CAAGACAAGCGACTACGTCAAAGAAGCCAAGCAGCTGCTGAAAGTGCAGAAGGCTTACCACCAG CTGGATCAGAGCTTCATCGATACTTATATCGACCTGCTGGAGACTCGGAGAACCTACTATGAGG GACCAGGAGAAGGGAGCCCCTTCGGATGGAAAGACATCAAGGAATGGTACGAGATGCTGATGGG ACATTGCACCTATTTTCCAGAAGAGCTGAGAAGCGTCAAGTACGCTTATAACGCAGATCTGTAC AACGCCCTGAATGACCTGAACAACCTGGTCATCACCAGGGATGAAAACGAGAAACTGGAATACT ATGAGAAGTTCCAGATCATCGAAAACGTGTTTAAGCAGAAGAAAAAGCCTACACTGAAACAGAT TGCTAAGGAGATCCTGGTCAACGAAGAGGACATCAAGGGCTACCGGGTGACAAGCACTGGAAAA CCAGAGTTCACCAATCTGAAAGTGTATCACGATATTAAGGACATCACAGCACGGAAAGAAATCA TTGAGAACGCCGAACTGCTGGATCAGATTGCTAAGATCCTGACTATCTACCAGAGCTCCGAGGA CATCCAGGAAGAGCTGACTAACCTGAACAGCGAGCTGACCCAGGAAGAGATCGAACAGATTAGT AATCTGAAGGGGTACACCGGAACACACAACCTGTCCCTGAAAGCTATCAATCTGATTCTGGATG AGCTGTGGCATACAAACGACAATCAGATTGCAATCTTTAACCGGCTGAAGCTGGTCCCAAAAAA GGTGGACCTGAGTCAGCAGAAAGAGATCCCAACCACACTGGTGGACGATTTCATTCTGTCACCC GTGGTCAAGCGGAGCTTCATCCAGAGCATCAAAGTGATCAACGCCATCATCAAGAAGTACGGCC TGCCCAATGATATCATTATCGAGCTGGCTAGGGAGAAGAACAGCAAGGACGCACAGAAGATGAT CAATGAGATGCAGAAACGAAACCGGCAGACCAATGAACGCATTGAAGAGATTATCCGAACTACC GGGAAAGAGAACGCAAAGTACCTGATTGAAAAAATCAAGCTGCACGATATGCAGGAGGGAAAGT GTCTGTATTCTCTGGAGGCCATCCCCCTGGAGGACCTGCTGAACAATCCATTCAACTACGAGGT CGATCATATTATCCCCAGAAGCGTGTCCTTCGACAATTCCTTTAACAACAAGGTGCTGGTCAAG CAGGAAGAGAACTCTAAAAAGGGCAATAGGACTCCTTTCCAGTACCTGTCTAGTTCAGATTCCA AGATCTCTTACGAAACCTTTAAAAAGCACATTCTGAATCTGGCCAAAGGAAAGGGCCGCATCAG CAAGACCAAAAAGGAGTACCTGCTGGAAGAGCGGGACATCAACAGATTCTCCGTCCAGAAGGAT TTTATTAACCGGAATCTGGTGGACACAAGATACGCTACTCGCGGCCTGATGAATCTGCTGCGAT CCTATTTCCGGGTGAACAATCTGGATGTGAAAGTCAAGTCCATCAACGGCGGGTTCACATCTTT TCTGAGGCGCAAATGGAAGTTTAAAAAGGAGCGCAACAAAGGGTACAAGCACCATGCCGAAGAT GCTCTGATTATCGCAAATGCCGACTTCATCTTTAAGGAGTGGAAAAAGCTGGACAAAGCCAAGA AAGTGATGGAGAACCAGATGTTCGAAGAGAAGCAGGCCGAATCTATGCCCGAAATCGAGACAGA ACAGGAGTACAAGGAGATTTTCATCACTCCTCACCAGATCAAGCATATCAAGGATTTCAAGGAC TACAAGTACTCTCACCGGGTGGATAAAAAGCCCAACAGAGAGCTGATCAATGACACCCTGTATA GTACAAGAAAAGACGATAAGGGGAATACCCTGATTGTGAACAATCTGAACGGACTGTACGACAA AGATAATGACAAGCTGAAAAAGCTGATCAACAAAAGTCCCGAGAAGCTGCTGATGTACCACCAT GATCCTCAGACATATCAGAAACTGAAGCTGATTATGGAGCAGTACGGCGACGAGAAGAACCCAC TGTATAAGTACTATGAAGAGACTGGGAACTACCTGACCAAGTATAGCAAAAAGGATAATGGCCC CGTGATCAAGAAGATCAAGTACTATGGGAACAAGCTGAATGCCCATCTGGACATCACAGACGAT TACCCTAACAGTCGCAACAAGGTGGTCAAGCTGTCACTGAAGCCATACAGATTCGATGTCTATC TGGACAACGGCGTGTATAAATTTGTGACTGTCAAGAATCTGGATGTCATCAAAAAGGAGAACTA CTATGAAGTGAATAGCAAGTGCTACGAAGAGGCTAAAAAGCTGAAAAAGATTAGCAACCAGGCA GAGTTCATCGCCTCCTTTTACAACAACGACCTGATTAAGATCAATGGCGAACTGTATAGGGTCA TCGGGGTGAACAATGATCTGCTGAACCGCATTGAAGTGAATATGATTGACATCACTTACCGAGA GTATCTGGAAAACATGAATGATAAGCGCCCCCCTCGAATTATCAAAACAATTGCCTCTAAGACT CAGAGTATCAAAAAGTACTCAACCGACATTCTGGGAAACCTGTATGAGGTGAAGAGCAAAAAGC ACCCTCAGATTATCAAAAAGGGC

(SEQ ID NO: 39)

If any of the above Cas9 sequences are fused with a peptide or polypeptide at the C- terminus, it is understood that the stop codon will be removed. Other Cas Molecules and Cas9 Polypeptides

Various types of Cas molecules or Cas9 polypeptides can be used to practice the inventions disclosed herein. In some embodiments, Cas molecules of Type II Cas systems are used. In other embodiments, Cas molecules of other Cas systems are used. For example, Type I or Type III Cas molecules may be used. Exemplary Cas molecules (and Cas systems) are described, e.g., in Haft et al, PLoS COMPUTATIONAL BIOLOGY 2005, 1(6): e60 and Makarova et al, NATURE REVIEW MICROBIOLOGY 2011, 9:467-477, the contents of both references are incorporated herein by reference in their entirety. Exemplary Cas molecules (and Cas systems) are also shown in Table 55.

Table 55: Cas Systems

Gene System type Name from Structure of Families (and Representatives name* or subtype Haft ei a/.^§ encoded protein superfamily) of

(PDB encoded

accessions)¹ protein

• Subtype I-B cse4, csh2, COG3649

• Subtype I-C cspl and cst2 (RAMP)

• Subtype I-E

cas8al • Subtype I- cmxl, cstl, NA BH0338-like LA3191 and

A** csx8, csx 13 PG2018

and CXXC- CXXC

cas8a2 • Subtype I- csa4 and csx9 NA PH0918 AF0070, AF1873,

A** MJ0385, PF0637,

PH0918 and SSO1401 cas8b • Subtype I- cshl and NA BH0338-like MTH1090 and

B** TM1802 TM1802 cas8c • Subtype I- csdl and csp2 NA BH0338-like BH0338

C**

cas9 • Type II** csnl and csxl2 NA COG3513 FTN_0757 and

SPyl046 cas 10 • Type III** cmr2, csml NA COG1353 MTH326, Rv2823c and csxll and TM1794 caslOd • Subtype I- csc3 NA COG1353 slr7011

D**

csyl • Subtype I- csyl NA yl724-like yl724

F**

csy2 • Subtype I-F csy2 NA (RAMP) yl725

csy3 • Subtype I-F csy3 NA (RAMP) yl726

csel • Subtype I- csel NA YgcL-like ygcL

E**

cse2 • Subtype I-E cse2 2ZCA YgcK-like ygcK

cscl • Subtype I-D cscl NA alrl563-like alrl563

(RAMP)

csc2 • Subtype I-D cscl and csc2 NA COG1337 slr7012

(RAMP)

csa5 • Subtype I-A csa5 NA AF1870 AF1870, MJ0380,

PF0643 and SS01398 csn2 • Subtype II- csn2 NA SPyl049-like SPyl049

A

csml • Subtype III- csml NA COG1421 MTH1081 and

A** SERP2460 csm.3 • Subtype III- csc2 and csm.3 NA COG1337 MTH1080 and

A (RAMP) SERP2459 csm.4 • Subtype Ill- csm4 NA COG 1567 MTH1079 and Table 55: Cas Systems

Gene System type Name from Structure of Families (and Representatives name* or subtype Hatt et al encoded protein superfamily) of

(PDB encoded

accessions)¹ protein

A (RAMP) SERP2458 csm5 • Subtype III- csm5 NA COG1332 MTH1078 and

A (RAMP) SERP2457 csm.6 • Subtype III- APE2256 and 2WTE COG1517 APE2256 and

A csm.6 SS01445 cmrl • Subtype Hi- cmrl NA COG 1367 PF1130

fi (RAMP)

cmr3 • Subtype Hi- cmr3 NA COG 1769 PF1128

fi (RAMP)

cmr4 • Subtype Hi- cmr4 NA COG1336 PF1126

fi (RAMP)

cmr5 • Subtype III- cmr5 2ZOP and 20EB COG3337 MTH324 and PF1125

B«

cmr6 • Subtype Hi- cmr6 NA COG 1604 PF1124

fi (RAMP)

csbl • Subtype I-U GSU0053 NA (RAMP) Balac_1306 and

GSU0053 csbl • Subtype I- NA NA (RAMP) Balac_1305 and

U GSU0054 csb3 • Subtype I-U NA NA (RAMP) Balac_1303 csx 17 • Subtype I-U NA NA NA Btus_2683 csx 14 • Subtype I-U NA NA NA GSU0052 csx 10 • Subtype I-U csx 10 NA (RAMP) Caur_2274 csx 16 • Subtype III- VVA1548 NA NA VVA1548

U

csaX • Subtype III- csaX NA NA SS01438

U

csx3 • Subtype III- csx3 NA NA AF1864

U

csxl • Subtype III- csa3, csxl, lXMX and 2171 COG1517 and MJ1666, NE0113,

U csx2, DXTHG, COG4006 PF1127 and TM1812

NE0113 and

TIGR02710

csx 15 • Unknown NA NA TTE2665 TTE2665 csfl • Type U csfl NA NA AFE_1038 csfl • Type U csfl NA (RAMP) AFE_1039 csf3 • Type U csf3 NA (RAMP) AFE_1040 csf4 • Type U csf4 NA NA AFE_1037 IV. Functional Analysis of Candidate Molecules

Candidate Cas9 molecules, candidate gRNA molecules, candidate Cas9 molecule/gRNA molecule complexes, can be evaluated by art-known methods or as described herein. For example, exemplary methods for evaluating the endonuclease activity of Cas9 molecule are described, e.g., in Jinek et al., SCIENCE 2012, 337(6096):816-821.

Binding and Cleavage Assay: Testing the endonuclease activity of Cas9 molecule

The ability of a Cas9 molecule/gRNA molecule complex to bind to and cleave a target nucleic acid can be evaluated in a plasmid cleavage assay. In this assay, synthetic or in vitro- transcribed gRNA molecule is pre-annealed prior to the reaction by heating to 95 °C and slowly cooling down to room temperature. Native or restriction digest-linearized plasmid DNA (300 ng (~8 nM)) is incubated for 60 min at 37°C with purified Cas9 protein molecule (50-500 nM) and gRNA (50-500 nM, 1: 1) in a Cas9 plasmid cleavage buffer (20 mM HEPES pH 7.5, 150 mM KC1, 0.5 mM DTT, 0.1 mM EDTA) with or without 10 mM MgCl₂. The reactions are stopped with 5X DNA loading buffer (30% glycerol, 1.2% SDS, 250 mM EDTA), resolved by a 0.8 or 1% agarose gel electrophoresis and visualized by ethidium bromide staining. The resulting cleavage products indicate whether the Cas9 molecule cleaves both DNA strands, or only one of the two strands. For example, linear DNA products indicate the cleavage of both DNA strands. Nicked open circular products indicate that only one of the two strands is cleaved.

Alternatively, the ability of a Cas9 molecule/gRNA molecule complex to bind to and cleave a target nucleic acid can be evaluated in an oligonucleotide DNA cleavage assay. In this assay, DNA oligonucleotides (10 pmol) are radiolabeled by incubating with 5 units T4 polynucleotide kinase and -3-6 pmol (-20-40 mCi) [γ-32Ρ]-ΑΤΡ in IX T4 polynucleotide kinase reaction buffer at 37°C for 30 min, in a 50

reaction. After heat inactivation (65°C for 20 min), reactions are purified through a column to remove unincorporated label. Duplex substrates (100 nM) are generated by annealing labeled oligonucleotides with equimolar amounts of unlabeled complementary oligonucleotide at 95 °C for 3 min, followed by slow cooling to room temperature. For cleavage assays, gRNA molecules are annealed by heating to 95°C for 30 s, followed by slow cooling to room temperature. Cas9 (500 nM final concentration) is pre- incubated with the annealed gRNA molecules (500 nM) in cleavage assay buffer (20 mM

HEPES pH 7.5, 100 mM KC1, 5 mM MgC12, 1 mM DTT, 5% glycerol) in a total volume of 9 μΐ. Reactions are initiated by the addition of 1 μΐ target DNA (10 nM) and incubated for 1 h at 37°C. Reactions are quenched by the addition of 20 μΐ of loading dye (5 mM EDTA, 0.025% SDS, 5% glycerol in formamide) and heated to 95°C for 5 min. Cleavage products are resolved on 12% denaturing polyacrylamide gels containing 7 M urea and visualized by phosphorimaging. The resulting cleavage products indicate that whether the complementary strand, the non- complementary strand, or both, are cleaved.

One or both of these assays can be used to evaluate the suitability of a candidate gRNA molecule or candidate Cas9 molecule.

Binding Assay: Testing the binding of Cas9 molecule to target DNA

Exemplary methods for evaluating the binding of Cas9 molecule to target DNA are described, e.g., in Jinek et al., SCIENCE 2012; 337(6096):816-821.

For example, in an electrophoretic mobility shift assay, target DNA duplexes are formed by mixing of each strand (10 nmol) in deionized water, heating to 95 °C for 3 min and slow cooling to room temperature. All DNAs are purified on 8% native gels containing IX TBE. DNA bands are visualized by UV shadowing, excised, and eluted by soaking gel pieces in DEPC-treated H₂0. Eluted DNA is ethanol precipitated and dissolved in DEPC-treated H₂0. DNA samples are 5' end labeled with [γ-32Ρ]-ΑΤΡ using T4 polynucleotide kinase for 30 min at 37°C. Polynucleotide kinase is heat denatured at 65°C for 20 min, and unincorporated radiolabel is removed using a column. Binding assays are performed in buffer containing 20 mM HEPES pH 7.5, 100 mM KC1, 5 mM MgCl₂, 1 mM DTT and 10% glycerol in a total volume of 10 μΐ. Cas9 protein molecule is programmed with equimolar amounts of pre-annealed gRNA molecule and titrated from 100 pM to 1 μΜ. Radiolabeled DNA is added to a final concentration of 20 pM. Samples are incubated for 1 h at 37°C and resolved at 4°C on an 8% native polyacrylamide gel containing IX TBE and 5 mM MgCl₂. Gels are dried and DNA visualized by

pho sphorimaging .

Differential Scanning Flourimetry (DSF)

The thermostability of Cas9-gRNA ribonucleoprotein (RNP) complexes can be measured via DSF. This technique measures the thermostability of a protein, which can increase under favorable conditions such as the addition of a binding RNA molecule, e.g., a gRNA. The assay is performed using two different protocols, one to test the best stoichiometric ratio of gRNA:Cas9 protein and another to determine the best solution conditions for RNP formation.

To determine the best solution to form RNP complexes, a 2uM solution of Cas9 in water+10x SYPRO Orange® (Life Techonologies cat#S-6650) and dispensed into a 384 well plate. An equimolar amount of gRNA diluted in solutions with varied pH and salt is then added. After incubating at room temperature for lO'and brief centrifugation to remove any bubbles,a Bio-Rad CFX384™ Real-Time System CI 000 Touch™ Thermal Cycler with the Bio-Rad CFX Manager software is used to run a gradient from 20°C to 90°C with a 1° increase in temperature every 10 seconds.

The second assay consists of mixing various concentrations of gRNA with 2uM Cas9 in optimal buffer from assay 1 above and incubating at RT for 10' in a 384 well plate. An equal volume of optimal buffer + lOx SYPRO Orange® (Life Techonologies cat#S-6650) is added and the plate sealed with Microseal® B adhesive (MSB-1001). Following brief centrifugation to remove any bubbles, a Bio-Rad CFX384™ Real-Time System CIOOO Touch™ Thermal Cycler with the Bio-Rad CFX Manager software is used to run a gradient from 20°C to 90°C with a 1° increase in temperature every 10 seconds.

V. Genome Editing Approaches

Mutations in the CFTR gene may be corrected using one of the approaches or pathways described herein, e.g., using HDR and/or NHEJ. In an embodiment, a mutation in the CFTR gene is corrected by homology directed repair (HDR) using a template nucleic acid (see Section V.l).

Also described herein are methods for targeted knockout of one or both alleles of the SCNN1A gene using NHEJ (see Section V.2).

V.l HDR Repair, HDR mediated knockin and Template Nucleic Acids

As described herein, nuclease-induced homology directed repair (HDR) can be used to alter a target sequence and correct (e.g., repair or edit) a mutation in the genome. While not wishing to be bound by theory, it is believed that alteration of the target sequence occurs by homology-directed repair (HDR) with a donor template or template nucleic acid. For example, the donor template or the template nucleic acid provides for alteration of the target sequence. It is contemplated that a plasmid donor can be used as a template for homologous recombination. It is further contemplated that a single stranded donor template can be used as a template for alteration of the target sequence by alternate methods of homology directed repair (e.g., single strand annealing) between the target sequence and the donor template. Donor template-effected alteration of a target sequence depends on cleavage by a Cas9 molecule. Cleavage by Cas9 can comprise a double strand break or one, two or more single strand breaks.

Mutations that can be corrected by HDR using a template nucleic acid include point mutations. In an embodiment, a point mutation can be corrected by either a single double-strand break or two single strand breaks. In an embodiment, a point mutation can be corrected by (1) a single double-strand break, (2) two single strand breaks, (3) two double stranded breaks with a break occurring on each side of the target sequence, or (4) four single stranded breaks with a pair of single stranded breaks occurring on each side of the target sequence.

Mutations in the CFTR gene that can be corrected (e.g., altered) by HDR with a template nucleic acid include deletion mutation at F508 (F508del) or point mutation at G551, e.g., G551D.

Double strand break mediated correction or knockin

In an embodiment, double strand cleavage is effected by a Cas9 molecule having cleavage activity associated with an HNH-like domain and cleavage activity associated with anRuvC-like domain, e.g., an N-terminal RuvC-like domain, e.g., a wild type Cas9. Such embodiments require only a single gRNA.

Single strand break mediated correction or knockin

In other embodiments, two single strand breaks, or nicks, are effected by a Cas9 molecule having nickase activity, e.g., cleavage activity associated with an HNH-like domain or cleavage activity associated with an N-terminal RuvC-like domain. Such embodiments require two gRNAs, one for placement of each single strand break. In an embodiment, the Cas9 molecule having nickase activity cleaves the strand to which the gRNA hybridizes, but not the strand that is complementary to the strand to which the gRNA hybridizes. In an embodiment, the Cas9 molecule having nickase activity does not cleave the strand to which the gRNA hybridizes, but rather cleaves the strand that is complementary to the strand to which the gRNA hybridizes. In an embodiment, the nickase has HNH activity, e.g., a Cas9 molecule having the RuvC activity inactivated, e.g., a Cas9 molecule having a mutation at D10, e.g., the D10A mutation. D10A inactivates RuvC; therefore, the Cas9 nickase has (only) HNH activity and will cut on the strand to which the gRNA hybridizes (e.g., the complementary strand, which does not have the NGG PAM on it). In other embodiments, a Cas9 molecule having an H840, e.g., an H840A, mutation can be used as a nickase. H840A inactivates HNH; therefore, the Cas9 nickase has (only) RuvC activity and cuts on the non-complementary strand (e.g., the strand that has the NGG PAM and whose sequence is identical to the gRNA). In other embodiments, a Cas9 molecule having an N863, e.g., an N863A mutation can be used as a nickase. N863A inactivates HNH therefore the Cas9 nickase has (only) RuvC activity and cuts on the non-complementary strand (the strand that has the PAM and whose sequence is identical to the gRNA).

In an embodiment, in which a nickase and two gRNAs are used to position two single strand nicks, one nick is on the + strand and one nick is on the - strand of the target nucleic acid. The PAMs are outwardly facing. The gRNAs can be selected such that the gRNAs are separated by, from about 0-50, 0-100, or 0-200 nucleotides. In an embodiment, there is no overlap between the target sequence that is complementary to the targeting domains of the two gRNAs. In an embodiment, the gRNAs do not overlap and are separated by as much as 50, 100, or 200 nucleotides. In an embodiment, the use of two gRNAs can increase specificity, e.g., by decreasing off-target binding (Ran et al., Cell 2013; 154(6): 1380-1389).

In an embodiment, a single nick can be used to induce HDR. It is contemplated herein that a single nick can be used to increase the ratio of HR to NHEJ at a given cleavage site.

Placement of double strand or single strand breaks relative to the target position

The double strand break or single strand break in one of the strands should be sufficiently close to the target position such that correction occurs. In an embodiment, the distance is not more than 50, 100, 200, 300, 350 or 400 nucleotides. While not wishing to be bound by theory, it is believed that the break should be sufficiently close to the target sequence such that the break is within the region that is subject to exonuclease-mediated removal during end resection. If the distance between the target sequence and a break is too great, the mutation may not be included in the end resection and, therefore, may not be corrected, as donor sequence may only be used to correct sequence within the end resection region. In an embodiment, in which a gRNA (unimolecular (or chimeric) or modular gRNA) and Cas9 nuclease induce a double strand break for the purpose of inducing HDR-mediated correction, the cleavage site is between 0 to 200 bp (e.g., 0 to 175, 0 to 150, 0 to 125, 0 to 100, 0 to 75, 0 to 50, 0 to 25, 25 to 200, 25 to 175, 25 to 150, 25 to 125, 25 to 100, 25 to 75, 25 to 50, 50 to 200, 50 to 175, 50 to 150, 50 to 125, 50 to 100, 50 to 75, 75 to 200, 75 to 175, 75 to 150, 75 to 125, 75 to 100 bp) away from the target position. In an embodiment, the cleavage site is between 0 to 100 bp (e.g., 0 to 75, 0 to 50, 0 to 25, 25 to 100, 25 to 75, 25 to 50, 50 to 100, 50 to 75 or 75 to 100 bp) away from the target position.

In an embodiment, in which two gRNAs (independently, unimolecular (or chimeric) or modular gRNA) complexing with Cas9 nickases induce two single strand breaks for the purpose of inducing HDR-mediated correction, the closer nick is between 0 to 200 bp (e.g., 0 to 175, 0 to 150, 0 to 125, 0 to 100, 0 to 75, 0 to 50, 0 to 25, 25 to 200, 25 to 175, 25 to 150, 25 to 125, 25 to 100, 25 to 75, 25 to 50, 50 to 200, 50 to 175, 50 to 150, 50 to 125, 50 to 100, 50 to 75, 75 to 200, 75 to 175, 75 to 150, 75 to 125, 75 to 100 bp) away from the target position and the two nicks will ideally be within 25 to 55 bp of each other (e.g., 25 to 50, 25 to 45, 25 to 40, 25 to 35, 25 to 30, 30 to 55, 30 to 50, 30 to 45, 30 to 40, 30 to 35, 35 to 55, 35 to 50, 35 to 45, 35 to 40, 40 to 55, 40 to 50, 40 to 45 bp) and no more than 100 bp away from each other (e.g., no more than 90, 80, 70, 60, 50, 40, 30, 20, 10 or 5 bp away from each other). In an embodiment, the cleavage site is between 0 to 100 bp (e.g., 0 to 75, 0 to 50, 0 to 25, 25 to 100, 25 to 75, 25 to 50, 50 to 100, 50 to 75 or 75 to 100 bp) away from the target position.

In one embodiment, two gRNAs, e.g., independently, unimolecular (or chimeric) or modular gRNA, are configured to position a double-strand break on both sides of a target position. In an alternate embodiment, three gRNAs, e.g., independently, unimolecular (or chimeric) or modular gRNA, are configured to position a double strand break (i.e., one gRNA complexes with a cas9 nuclease) and two single strand breaks or paired single stranded breaks (i.e., two gRNAs complex with Cas9 nickases) on either side of the target position. In another embodiment, four gRNAs, e.g., independently, unimolecular (or chimeric) or modular gRNA, are configured to generate two pairs of single stranded breaks (i.e., two pairs of two gRNAs complex with Cas9 nickases) on either side of the target position. The double strand break(s) or the closer of the two single strand nicks in a pair will ideally be within 0-500 bp of the target position (e.g., no more than 450, 400, 350, 300, 250, 200, 150, 100, 50 or 25 bp from the target position). When nickases are used, the two nicks in a pair are within 25-55 bp of each other (e.g., between 25 to 50, 25 to 45, 25 to 40, 25 to 35, 25 to 30, 50 to 55, 45 to 55, 40 to 55, 35 to 55, 30 to 55, 30 to 50, 35 to 50, 40 to 50 , 45 to 50, 35 to 45, or 40 to 45 bp) and no more than 100 bp away from each other (e.g., no more than 90, 80, 70, 60, 50, 40, 30, 20 or 10 bp). In an embodiment, the gRNAs are configured to place a single strand break on either side of the target position. In an embodiment, the gRNAs are configured to place a single strand break on the same side (either 5' or 3') of the target position.

Regardless of whether a break is a double strand or a single strand break, the gRNA should be configured to avoid unwanted target chromosome elements, such as repeated elements, e.g., an Alu repeat, in the target domain. In addition, a break, whether a double strand or a single strand break, should be sufficiently distant from any sequence that should not be altered. For example, cleavage sites positioned within introns should be sufficiently distant from any intron/exon border, or naturally occurring splice signal, to avoid alteration of the exonic sequence or unwanted splicing events.

Length of the homology arms

The homology arm should extend at least as far as the region in which end resection may occur, e.g., in order to allow the resected single stranded overhang to find a complementary region within the donor template. The overall length could be limited by parameters such as plasmid size or viral packaging limits. In an embodiment, a homology arm does not extend into repeated elements, e.g., Alu repeats, LINE repeats.

Exemplary homology arm lengths include a least 50, 100, 250, 500, 750 or 1000 nucleotides.

Target position, as used herein, refers to a site on a target nucleic acid (e.g., the chromosome) that is modified by a Cas9 molecule-dependent process. For example, the target position can be a modified Cas9 molecule cleavage of the target nucleic acid and template nucleic acid directed modification, e.g., correction, of the target position. In an embodiment, a target position can be a site between two nucleotides, e.g., adjacent nucleotides, on the target nucleic acid into which one or more nucleotides is added. The target position may comprise one or more nucleotides that are altered, e.g., corrected, by a template nucleic acid. In an

embodiment, the target position is within a target sequence (e.g., the sequence to which the gRNA binds). In an embodiment, a target position is upstream or downstream of a target sequence (e.g., the sequence to which the gRNA binds).

A template nucleic acid, as that term is used herein, refers to a nucleic acid sequence which can be used in conjunction with a Cas9 molecule and a gRNA molecule to alter the structure of a target position. In an embodiment, the target nucleic acid is modified to have the some or all of the sequence of the template nucleic acid, typically at or near cleavage site(s). In an embodiment, the template nucleic acid is single stranded. In an alternate embodiment, the template nucleic acid is double stranded. In an embodiment, the template nucleic acid is DNA, e.g., double stranded DNA. In an alternate embodiment, the template nucleic acid is single stranded DNA. In an embodiment, the template nucleic acid is encoded on the same vector backbone, e.g. AAV genome, plasmid DNA, as the Cas9 and gRNA. In an embodiment, the template nucleic acid is excised from a vector backbone in vivo, e.g., it is flanked by gRNA recognition sequences.

In an embodiment, the template nucleic acid alters the structure of the target position by participating in a homology directed repair event. In an embodiment, the template nucleic acid alters the sequence of the target position. In an embodiment, the template nucleic acid results in the incorporation of a modified, or non-naturally occurring base into the target nucleic acid.

Typically, the template sequence undergoes a breakage mediated or catalyzed recombination with the target sequence. In an embodiment, the template nucleic acid includes sequence that corresponds to a site on the target sequence that is cleaved by an eaCas9 mediated cleavage event. In an embodiment, the template nucleic acid includes sequence that corresponds to both, a first site on the target sequence that is cleaved in a first Cas9 mediated event, and a second site on the target sequence that is cleaved in a second Cas9 mediated event.

In an embodiment, the template nucleic acid can include sequence which results in an alteration in the coding sequence of a translated sequence, e.g., one which results in the substitution of one amino acid for another in a protein product, e.g., transforming a mutant allele into a wild type allele, transforming a wild type allele into a mutant allele, and/or introducing a stop codon, insertion of an amino acid residue, deletion of an amino acid residue, or a nonsense mutation.

In another embodiment, the template nucleic acid can include sequence which results in an alteration in a non-coding sequence, e.g., an alteration in an exon or in a 5' or 3' non- translated or non-transcribed region. Such alterations include an alteration in a control element, e.g., a promoter, enhancer, and an alteration in a cis-acting or trans-acting control element.

A template nucleic acid having homology with a target position in the CFTR gene can be used to alter the structure of a target sequence. The template sequence can be used to alter an unwanted structure, e.g., an unwanted or mutant nucleotide.

A template nucleic acid comprises the following components:

[5' homology arm] -[replacement sequence] -[3' homology arm].

The homology arms provide for recombination into the chromosome, thus replacing the undesired element, e.g., a mutation or signature, with the replacement sequence. In an embodiment, the homology arms flank the most distal cleavage sites.

In an embodiment, the 3' end of the 5' homology arm is the position next to the 5' end of the replacement sequence. In an embodiment, the 5' homology arm can extend at least 10, 20, 30, 40, 50, 100, 200, 300, 400, 500, 600, 700, 800, 900, 1000, 1500, or 2000 nucleotides 5' from the 5' end of the replacement sequence.

In an embodiment, the 5' end of the 3' homology arm is the position next to the 3' end of the replacement sequence. In an embodiment, the 3' homology arm can extend at least 10, 20, 30, 40, 50, 100, 200, 300, 400, 500, 600, 700, 800, 900, 1000, 1500, or 2000 nucleotides 3' from the 3' end of the replacement sequence.

Exemplary Template Nucleic Acids

Exemplary template nucleic acids (also referred to herein as donor constructs) to correct a mutation, e.g., F508del target position in the CFTR gene, are provided.

Suitable sequence for the 5' homology arm can be selected from (e.g., includes a portion of) or include the following sequence:

AAAATACAAAAAATTAGCCAGACGTGATGGCGGGTGCCCGTAGTCCCAGCTACTCGGGAGGCTG AGGCAGGAGAATGGCGTGAACCCAGGAGGCAGAACTTGCAGTGAGCCGAGATCGCGCCACTGCA CTCTAGCCTGGGTGACAGAGTGAGACTCTGTCTCTAAATAAATAAATAAATAAATAAATAAATA AATAAAATCAGTGCTTTTTCTTCCTCTGCTACCTCCTTTCCTTCTACTCAGTTTTAGTCAGTAG TATTATCTTTTTTCAGATTTATCTTTGTATTGTTAAATCTGCTTATGCTTCTATTACTTTATTT ATTAGCTTTAAATGATACCTTTTGACTTTCAGCTTTTCTTAATAAAGCAATCAGCAAATTTCCT TTACACTCCACACTTATACCCCATTTCCTTTGTTTGTTTATTTGGTTTTTACTTCTAACTTTTC TTATTGTCAGGACATATAACATATTTAAACTTTGTTTTTCAACTCGAATTCTGCCATTAGTTTT

AATTTTTGTTCACAGTTATATAAATCTTTGTTCACTGATAGTCCTTTTGTACTATCATCTCTTA

AATGACTTTATACTCCAAGAAAGGCTCATGGGAACAATATTACCTGAATATGTCTCTATTACTT

AATCTGTACCTAATAATATGAAGGTAATCTACTTTGTAGGATTTCTGTGAAGATTAAATAAATT

AATATAGTTAAAGCACATAGAACAGCACTCGACACAGAGTGAGCACTTGGCAACTGTTAGCTGT

TACTAACCTTTCCCATTCTTCCTCCAAACCTATTCCAACTATCTGAATCATGTGCCCCTTCTCT

GTGAACCTCTATCATAATACTTGTCACACTGTATTGTAATTGTCTCTTTTACTTTCCCTTGTAT

CTTTTGTGCATAGCAGAGTACCTGAAACAGGAAGTATTTTAAATATTTTGAATCAAATGAGTTA

ATAGAATCTTTACAAATAAGAATATACACTTCTGCTTAGGATGATAATTGGAGGCAAGTGAATC

CTGAGCGTGATTTGATAATGACCTAATAATGATGGGTTTTATTTCCAGACTTCACTTCTAATGG

TGATTATGGGAGAACTGGAGCCTTCAGAGGGTAAAATTAAGCACAGTGGAAGAATTTCATTCTG

TTCTCAGTTTTCCTGGATTATGCCTGGCACCATTAAAGAAAATATCAT

SEQ ID NO: 27266 (5 Ή arm)

Suitable sequence for the 3' homology arm can be selected from (e.g., includes a portion of) or include the following sequence:

TGGTGTTTCCTATGATGAATATAGATACAGAAGCGTCATCAAAGCATGCCAACTAGAAGAGGTA AGAAACTATGTGAAAACTTTTTGATTATGCATATGAACCCTTCACACTACCCAAATTATATATT TGGCTCCATATTCAATCGGTTAGTCTACATATATTTATGTTTCCTCTATGGGTAAGCTACTGTG AATGGATCAATTAATAAAACACATGACCTATGCTTTAAGAAGCTTGCAAACACATGAAATAAAT GCAATTTATTTTTTAAATAATGGGTTCATTTGATCACAATAAATGCATTTTATGAAATGGTGAG AATTTTGTTCACTCATTAGTGAGACAAACGTCCTCAATGGTTATTTATATGGCATGCATATAAG TGATATGTGGTATCTTTTTAAAAGATACCACAAAATATGCATCTTTAAAAATATACTCCAAAAA TTATTAAGATTATTTTAATAATTTTAATAATACTATAGCCTAATGGAATGAGCATTGATCTGCC AGCAGAGAATTAGAGGGGTAAAATTGTGAAGATATTGTATCCCTGGCTTTGAACAAATACCATA TAACTTCTAGTGACTGCAATTCTTTGATGCAGAGGCAAAATGAAGATGATGTCATTACTCATTT CACAACAATATTGGAGAATGAGCTAATTATCTGAAAATTACATGAAGTATTCCAAGAGAAACCA GTATATGGATCTTGTGCTGTTCACTATGTAAATTGTGTGATGGTGGGTTCAGTAGTTATTGCTG TAAATGTTAGGGCAGGGAATATGTTACTATGAAGTTTATTGACAGTATACTCCAAATAGTGTTT GTGATTCAAAAGCAATATCTTTGATAGTTGGCATTTGCAATTCCTTTATATAATCTTTTATGAA AAAAATTGCAGAGAAAGTAAAATGTAGCTTAAAATACAGTATCCAAAAAAATGGAAAAGGGCAA ACCGTGGATTAGATAGAAATGGCAATTCTTATAAAAAGGGTTGCATGCTTACATGAATGGCTTT CCATGTATATACTCAGTCATTCAACAGTTTTTTTTTTAGAGCCCCATTCTTATTTTTTATACAC TTTGAGAGCATAATGAAAAGAAAAGCTACCTGCAAAAGTTTTGGACTTACCTCAAAGAGGATAT

ACTTCATTCCTCAAAAGGCCTTCTTCCAGGAATAGTATTTCATAACCT

SEQ ID NO: 27267 (3Ή arm)

In an embodiment, the replacement sequence comprises or consists of CTT residues.

In an embodiment, to correct a mutation, e.g., F508del target site in the CFTR gene, the homology arms, e.g., the 5' and 3' homology arms, may each comprise about 1000 base pairs (bp) of sequence flanking the most distal gRNAs (e.g., 1200bp of sequence on either side of the mutation). The 5' homology arm is shown as bold sequence, the inserted bases to correct the F508del mutation is shown as lower case sequence, and the 3' homology arm is shown as no emphasis capitalized sequence.

AAAATACAAAAAATTAGCCAGACGTGATGGCGGGTGCCCGTAGTCCCAGCTACTCGGGAGGCTG AGGCAGGAGAATGGCGTGAACCCAGGAGGCAGAACTTGCAGTGAGCCGAGATCGCGCCACTGCA CTCTAGCCTGGGTGACAGAGTGAGACTCTGTCTCTAAATAAATAAATAAATAAATAAATAAATA AATAAAATCAGTGCTTTTTCTTCCTCTGCTACCTCCTTTCCTTCTACTCAGTTTTAGTCAGTAG TATTATCTTTTTTCAGATTTATCTTTGTATTGTTAAATCTGCTTATGCTTCTATTACTTTATTT ATTAGCTTTAAATGATACCTTTTGACTTTCAGCTTTTCTTAATAAAGCAATCAGCAAATTTCCT TTACACTCCACACTTATACCCCATTTCCTTTGTTTGTTTATTTGGTTTTTACTTCTAACTTTTC TTATTGTCAGGACATATAACATATTTAAACTTTGTTTTTCAACTCGAATTCTGCCATTAGTTTT AATTTTTGTTCACAGTTATATAAATCTTTGTTCACTGATAGTCCTTTTGTACTATCATCTCTTA AATGACTTTATACTCCAAGAAAGGCTCATGGGAACAATATTACCTGAATATGTCTCTATTACTT AATCTGTACCTAATAATATGAAGGTAATCTACTTTGTAGGATTTCTGTGAAGATTAAATAAATT AATATAGTTAAAGCACATAGAACAGCACTCGACACAGAGTGAGCACTTGGCAACTGTTAGCTGT TACTAACCTTTCCCATTCTTCCTCCAAACCTATTCCAACTATCTGAATCATGTGCCCCTTCTCT GTGAACCTCTATCATAATACTTGTCACACTGTATTGTAATTGTCTCTTTTACTTTCCCTTGTAT CTTTTGTGCATAGCAGAGTACCTGAAACAGGAAGTATTTTAAATATTTTGAATCAAATGAGTTA ATAGAATCTTTACAAATAAGAATATACACTTCTGCTTAGGATGATAATTGGAGGCAAGTGAATC CTGAGCGTGATTTGATAATGACCTAATAATGATGGGTTTTATTTCCAGACTTCACTTCTAATGG TGATTATGGGAGAACTGGAGCCTTCAGAGGGTAAAATTAAGCACAGTGGAAGAATTTCATTCTG TTCTCAGTTTTCCTGGATTATGCCTGGCACCATTAAAGAAAATATCATct tTGGTGTTTCCTAT GATGAATATAGATACAGAAGCGTCATCAAAGCATGCCAACTAGAAGAGGTAAGAAACTATGTGA AAACTTTTTGATTATGCATATGAACCCTTCACACTACCCAAATTATATATTTGGCTCCATATTC AATCGGTTAGTCTACATATATTTATGTTTCCTCTATGGGTAAGCTACTGTGAATGGATCAATTA ATAAAACACATGACCTATGCTTTAAGAAGCTTGCAAACACATGAAATAAATGCAATTTATTTTT TAAATAATGGGTTCATTTGATCACAATAAATGCATTTTATGAAATGGTGAGAATTTTGTTCACT CATTAGTGAGACAAACGTCCTCAATGGTTATTTATATGGCATGCATATAAGTGATATGTGGTAT CTTTTTAAAAGATACCACAAAATATGCATCTTTAAAAATATACTCCAAAAATTATTAAGATTAT TTTAATAATTTTAATAATACTATAGCCTAATGGAATGAGCATTGATCTGCCAGCAGAGAATTAG AGGGGTAAAATTGTGAAGATATTGTATCCCTGGCTTTGAACAAATACCATATAACTTCTAGTGA CTGCAATTCTTTGATGCAGAGGCAAAATGAAGATGATGTCATTACTCATTTCACAACAATATTG GAGAATGAGCTAATTATCTGAAAATTACATGAAGTATTCCAAGAGAAACCAGTATATGGATCTT GTGCTGTTCACTATGTAAATTGTGTGATGGTGGGTTCAGTAGTTATTGCTGTAAATGTTAGGGC AGGGAATATGTTACTATGAAGTTTATTGACAGTATACTCCAAATAGTGTTTGTGATTCAAAAGC AATATCTTTGATAGTTGGCATTTGCAATTCCTTTATATAATCTTTTATGAAAAAAATTGCAGAG AAAGTAAAATGTAGCTTAAAATACAGTATCCAAAAAAATGGAAAAGGGCAAACCGTGGATTAGA TAGAAATGGCAATTCTTATAAAAAGGGTTGCATGCTTACATGAATGGCTTTCCATGTATATACT CAGTCATTCAACAGTTTTTTTTTTAGAGCCCCATTCTTATTTTTTATACACTTTGAGAGCATAA TGAAAAGAAAAGCTACCTGCAAAAGTTTTGGACTTACCTCAAAGAGGATATACTTCATTCCTCA AAAGGCCTTCTTCCAGGAATAGTATTTCATAACCT

(Template Construct 1; SEQ ID NO: 27268)

As described below in Table 49, shorter homology arms, e.g., 5' and/or 3' homology arms may be used.

It is contemplated herein that one or both homology arms may be shortened to avoid including certain sequence repeat elements, e.g., Alu repeats, LINE elements. For example, a 5' homology arm may be shortened to avoid a sequence repeat element. In other embodiments, a 3' homology arm may be shortened to avoid a sequence repeat element. In some embodiments, both the 5' and the 3' homology arms may be shortened to avoid including certain sequence repeat elements.

In an embodiment, to correct F508del mutation in the CFTR gene, the 5' homology arm may be shortened less than 500 nucleotides, e.g., approximately 450 nucleotides, e.g., 428 nucleotides, to avoid inclusion of a LINE repeat element in the 5' homology arm. The 5' homology arm is shown as bold sequence, the inserted bases to correct the F508del mutation is shown as lower case sequence, and the 3' homology arm is shown as no emphasis capitalized sequence.

AACCTTTCCCATTCTTCCTCCAAACCTATTCCAACTATCTGAATCATGTGCCCCTTCTCTGTGA

ACCTCTATCATAATACTTGTCACACTGTATTGTAATTGTCTCTTTTACTTTCCCTTGTATCTTT

TGTGCATAGCAGAGTACCTGAAACAGGAAGTATTTTAAATATTTTGAATCAAATGAGTTAATAG

AATCTTTACAAATAAGAATATACACTTCTGCTTAGGATGATAATTGGAGGCAAGTGAATCCTGA

GCGTGATTTGATAATGACCTAATAATGATGGGTTTTATTTCCAGACTTCACTTCTAATGGTGAT

TATGGGAGAACTGGAGCCTTCAGAGGGTAAAATTAAGCACAGTGGAAGAATTTCATTCTGTTCT

CAGTTTTCCTGGATTATGCCTGGCACCATTAAAGAAAATATCATcttTGGTGTTTCCTATGATG

AATATAGATACAGAAGCGTCATCAAAGCATGCCAACTAGAAGAGGTAAGAAACTATGTGAAAAC

TTTTTGATTATGCATATGAACCCTTCACACTACCCAAATTATATATTTGGCTCCATATTCAATC

GGTTAGTCTACATATATTTATGTTTCCTCTATGGGTAAGCTACTGTGAATGGATCAATTAATAA

AACACATGACCTATGCTTTAAGAAGCTTGCAAACACATGAAATAAATGCAATTTATTTTTTAAA

TAATGGGTTCATTTGATCACAATAAATGCATTTTATGAAATGGTGAGAATTTTGTTCACTCATT

AGTGAGACAAACGTCCTCAATGGTTATTTATATGGCATGCATATAAGTGATATGTGGTATCTTT

TTAAAAGATACCACAAAATATGCATCTTTAAAAATATACTCCAAAAATTATTAAGATTATTTTA

ATAATTTTAATAATACTATAGCCTAATGGAATGAGCATTGATCTGCCAGCAGAGAATTAGAGGG

GTAAAATTGTGAAGATATTGTATCCCTGGCTTTGAACAAATACCATATAACTTCTAGTGACTGC

AATTCTTTGATGCAGAGGCAAAATGAAGATGATGTCATTACTCATTTCACAACAATATTGGAGA

ATGAGCTAATTATCTGAAAATTACATGAAGTATTCCAAGAGAAACCAGTATATGGATCTTGTGC

TGTTCACTATGTAAATTGTGTGATGGTGGGTTCAGTAGTTATTGCTGTAAATGTTAGGGCAGGG

AATATGTTACTATGAAGTTTATTGACAGTATACTCCAAATAGTGTTTGTGATTCAAAAGCAATA

TCTTTGATAGTTGGCATTTGCAATTCCTTTATATAATCTTTTATGAAAAAAATTGCAGAGAAAG

TAAAATGTAGCTTAAAATACAGTATCCAAAAAAATGGAAAAGGGCAAACCGTGGATTAGATAGA

AATGGCAATTCTTATAAAAAGGGTTGCATGCTTACATGAATGGCTTTCCATGTATATACTCAGT

CATTCAACAGTTTTTTTTTTAGAGCCCCATTCTTATTTTTTATACACTTTGAGAGCATAATGAA

AAGAAAAGCTACCTGCAAAAGTTTTGGACTTACCTCAAAGAGGATATACTTCATTCCTCAAAAG

GCCTTCTTCCAGGAATAGTATTTCATAACCT

(Template Construct 2; SEQ ID NO: 27269)

In an embodiment, to correct F508del mutation in the CFTR gene, the 5' homology arm may be shortened to approximately 500 nucleotides. The 5' homology arm is shown as bold sequence, the inserted bases to correct the F508del mutation is shown as lower case sequence, and the 3' homology arm is shown as no emphasis capitalized sequence. AATTAATATAGTTAAAGCACATAGAACAGCACTCGACACAGAGTGAGCACTTGGCAACTGTTAG

CTGTTACTAACCTTTCCCATTCTTCCTCCAAACCTATTCCAACTATCTGAATCATGTGCCCCTT

CTCTGTGAACCTCTATCATAATACTTGTCACACTGTATTGTAATTGTCTCTTTTACTTTCCCTT

GTATCTTTTGTGCATAGCAGAGTACCTGAAACAGGAAGTATTTTAAATATTTTGAATCAAATGA

GTTAATAGAATCTTTACAAATAAGAATATACACTTCTGCTTAGGATGATAATTGGAGGCAAGTG

AATCCTGAGCGTGATTTGATAATGACCTAATAATGATGGGTTTTATTTCCAGACTTCACTTCTA

ATGGTGATTATGGGAGAACTGGAGCCTTCAGAGGGTAAAATTAAGCACAGTGGAAGAATTTCAT

TCTGTTCTCAGTTTTCCTGGATTATGCCTGGCACCArrAAAGAAAATArCArctt TGGTGTTTC

CTATGATGAATATAGATACAGAAGCGTCATCAAAGCATGCCAACTAGAAGAGGTAAGAAACTAT

GTGAAAACTTTTTGATTATGCATATGAACCCTTCACACTACCCAAATTATATATTTGGCTCCAT

ATTCAATCGGTTAGTCTACATATATTTATGTTTCCTCTATGGGTAAGCTACTGTGAATGGATCA

ATTAATAAAACACATGACCTATGCTTTAAGAAGCTTGCAAACACATGAAATAAATGCAATTTAT

TTTTTAAATAATGGGTTCATTTGATCACAATAAATGCATTTTATGAAATGGTGAGAATTTTGTT

CACTCATTAGTGAGACAAACGTCCTCAATGGTTATTTATATGGCATGCATATAAGTGATATGTG

GTATCTTTTTAAAAGATACCACAAAATATGCATCTTTAAAAATATACTCCAAAAATTATTAAGA

T T AT T T TAATAAT T T T AAT AAT AC T AT AGCC T AAT GGAAT GAG

(Template Construct 3; SEQ ID NO: 27270)

It is contemplated herein that, in an embodiment, template nucleic acids for correcting a mutation may designed for use as a single- stranded oligonucleotide (ssODN). When using a ssODN, 5' and 3' homology arms may range up to about 200 base pairs (bp) in length, e.g., at least 25, 50, 75, 100, 125, 150, 175, or 200 bp in length. Longer homology arms are also contemplated for ssODNs as improvements in oligonucleotide synthesis continue to be made.

In an embodiment, an ssODN may be used to correct a mutation, e.g., F508del target site in the CFTR gene. For example, the ssODN may include 5' and 3' homology arms as shown below. The 5' homology arm is shown as bold sequence, the inserted bases to correct the F508del mutation is shown as lower case sequence, and the 3' homology arm is shown as no emphasis capitalized sequence.

TAAGCACAGTGGAAGAATTTCATTCTGTTCTCAGTTTTCCTGGATTATGCCTGGCACCATTAAA GAAAATATCATctt TGGTGTTTCCTATGATGAATATAGATACAGAAGCGTCATCAAAGCATGCC AAC T AG AAG AG G T AAG AAAC T AT G T (Template Construct 4; SEQ ID NO: 27271) Exemplary template nucleic acids (also referred to herein as donor constructs) to correction a mutation, e.g., G542X target site in the CFTR gene, are provided.

Suitable sequence for the 5' homology arm can be selected from (e.g., includes a portion of) or include the following sequence:

TGTCCATATGGTAGATAAATGGAACAAATGAATAACAGAAGTAACCATTTTGATACTTTAGATA

TAGATAATATTGGATTATTTCTGGATTGTGAAAGAAGAAGGAAGAAGCATATGGAAGAGAAGTT

TTAGTAGAGGGGAGGAAGGAGGAGGTGGAAACGAATGTACAAGGATGGGAGGAGAAAAGGGAGA

GAGACTTTTTTTTTTTTAAGGCGAGAGTTTACTACCTATCTAACTCTTCGCATTCTTGAAGTCT

CAGACCAAATCCCATCGGTTTGAAAGCCTCTAGGGTATTCTATCTATTGTATACTTCTGTTATG

TACAAAATTAATTTGCCAATTAATTGTGAACTGTTTTATAAACTATCTTAAAATGGTTAGTTAA

ATCTTTGGGATAGTATTTAGCTTTCTCCAGGATTATGACTTACCTTCTAAATTAGACATACAAT

GCCTAGGAGTCAAGGACTATTTTGCATAAATTCCAGTCTTCTTTTACAATGCCTAGAATGATTG

TTACCACAGAAATATTCATTACCTGGGAGAAAGGATGACAGGAGGGGCAGAATGAATGGAGAGA

GGTCGTGAGAATGAGGTGCTGAGGATGGACGAGGAAGAAAGCTGTTTTAGTTGGGAGGATAGGT

GACAGAAGCATGGAAAGGAATTGCCTTGGACCCATGGAAGCCCAGTGAAGATACTTAGATCCTG

CAGGGGTGTGAATAATGTTCTTTTAGTTTCTCTTCTTAGGAGGTTTGTTCATTTTGGGAGATTT

CTTTTGAAAAGAGTGAACTTAAATTGGAGAAAAGTACATTTTAGTATGTTGATAACATTTGAAT

TTGTAAAATGGACCTATGGATGATCTACACATATTTATATACCCATAAATATACACATATTTTA

ATTTTTGGTATTTTATAATTATTATTTAATGATCATTCATGACATTTTAAAAATTACAGAAAAA

TTTACATCTAAAATTTCAGCAATGTTGTTTTTGACCAACTAAATAAATTGCATTTGAAATAATG

GAGATGCAATGTTCAAAATTTCAACTGTGGTTAAAGCAATAGTGTGATATATGATTACATTAGA

AGGAAGATGTGCCTTTCAAATTCAGATTGAGCATACTAAAAGTGACTCTCTAATTTTCTATTTT

TGGTAATAGGACATCTCCAAGTTTGCAGAGAAAGACAATATAGTTCTT

SEQ ID NO: 27272 (5Ή arm)

Suitable sequence for the 3' homology arm can be selected from (e.g., includes a portion of) or include the following sequence:

GAGAAGGTGGAATCACACTGAGTGGAGGTCAACGAGCAAGAATTTCTTTAGCAAGGTGAATAAC TAATTATTGGTCTAGCAAGCATTTGCTGTAAATGTCATTCATGTAAAAAAATTACAGACATTTC TCTATTGCTTTATATTCTGTTTCTGGAATTGAAAAAATCCTGGGGTTTTATGGCTAGTGGGTTA AGAATCACATTTAAGAACTATAAATAATGGTATAGTATCCAGATTTGGTAGAGATTATGGTTAC TCAGAATCTGTGCCCGTATCTTGGTGTCAGTGTATTTGTTTGCCTCATAGTATAGTTTACTACA AATGGAAAACTCTAGGATTCTGCATAATACTGGACAGAGAAGATGTAAATATCTGTTAGTTCCA TCATAGACCCTGCCACTCCAATGTACACACCAGCTTTAGGCTTCTTGGTATAGATAAACATACA

TTTTCAAAATTTTTCATCATAATTTTCATAACAAAATAGGAAGGCAAATGATGTCACTTGGCTT

AAAATCTATAATATTTAAAATAAACAGGACAAATGCATTAACATTGTTGGGGGAGGAGGTCCCT

TAGTAGAAACACTCTTGGTCCAAGCATTTTAAAGCTGTCAAAGAGATGTAAATATAGATAATGT

ATGTCAAGGAGAGAGCTTTGTGGTTAAACTGTAACTTTCAGTTTAAACAATTATTGGTGACTCT

GATGTCAAATGTTTCTCAAGCTTTATCTGAACAAAATTCTTCTCACTTTGTTGCCAAAGTCGTT

AACAAGAAATCACATTGACTCATTGATGTTTTGGCTCCTTTCCCTTACTTTCTGTTGCTTTCCA

AAAGCTGAGACAGGAAACTAACCCTAACTGAGCACCTGCAATTGCCTGGTAGTATTCTAGTCAT

GTGTGTACTTTTGTGTGTATGTAATCCCCTTACAGCTCTGCAAAGTAAGAATTGTTCTCCCTGC

TTTACAGAAGAGATCATAAGATAATTGAGGCTGTTAGATGTTAACTTGCCAAAAGCCATACAGG

AAAATGGTAGAGTCACAGTTTGAACCAGGTCCTTTTGATTCTTTACATTAAACCATGCTTTGAT

CTTGGAAATACACTGTAAGGCAATAAATCAATAGATACGGATAATTCACAGGCTTCTAAATAAA

TGGAAGTTGATTGTTTTTATCTGTGAGCCAAAGTAAGACTTATTCTAA

SEQ ID NO: 27273 (3Ή arm)

In an embodiment, the replacement sequence comprises or consists of a Guanine (G) residue.

In an embodiment, to correct a mutation, e.g., G542X target site in the CFTR gene, the homology arms, e.g., the 5' and 3' homology arms, may each comprise about 1000 base pairs (bp) of sequence flanking the most distal gRNAs (e.g., 1200bp of sequence on either side of the mutation). The 5' homology arm is shown as bold sequence, the inserted base to correct the G542X mutation is shown as lower case sequence, and the 3' homology arm is shown as no emphasis capitalized sequence.

TGTCCATATGGTAGATAAATGGAACAAATGAATAACAGAAGTAACCATTTTGATACTTTAGATA TAGATAATATTGGATTATTTCTGGATTGTGAAAGAAGAAGGAAGAAGCATATGGAAGAGAAGTT TTAGTAGAGGGGAGGAAGGAGGAGGTGGAAACGAATGTACAAGGATGGGAGGAGAAAAGGGAGA GAGACTTTTTTTTTTTTAAGGCGAGAGTTTACTACCTATCTAACTCTTCGCATTCTTGAAGTCT CAGACCAAATCCCATCGGTTTGAAAGCCTCTAGGGTATTCTATCTATTGTATACTTCTGTTATG TACAAAATTAATTTGCCAATTAATTGTGAACTGTTTTATAAACTATCTTAAAATGGTTAGTTAA ATCTTTGGGATAGTATTTAGCTTTCTCCAGGATTATGACTTACCTTCTAAATTAGACATACAAT GCCTAGGAGTCAAGGACTATTTTGCATAAATTCCAGTCTTCTTTTACAATGCCTAGAATGATTG TTACCACAGAAATATTCATTACCTGGGAGAAAGGATGACAGGAGGGGCAGAATGAATGGAGAGA GGTCGTGAGAATGAGGTGCTGAGGATGGACGAGGAAGAAAGCTGTTTTAGTTGGGAGGATAGGT

GACAGAAGCATGGAAAGGAATTGCCTTGGACCCATGGAAGCCCAGTGAAGATACTTAGATCCTG

CAGGGGTGTGAATAATGTTCTTTTAGTTTCTCTTCTTAGGAGGTTTGTTCATTTTGGGAGATTT

CTTTTGAAAAGAGTGAACTTAAATTGGAGAAAAGTACATTTTAGTATGTTGATAACATTTGAAT

TTGTAAAATGGACCTATGGATGATCTACACATATTTATATACCCATAAATATACACATATTTTA

ATTTTTGGTATTTTATAATTATTATTTAATGATCATTCATGACATTTTAAAAATTACAGAAAAA

TTTACATCTAAAATTTCAGCAATGTTGTTTTTGACCAACTAAATAAATTGCATTTGAAATAATG

GAGATGCAATGTTCAAAATTTCAACTGTGGTTAAAGCAATAGTGTGATATATGATTACATTAGA

AGGAAGATGTGCCTTTCAAATTCAGATTGAGCATACTAAAAGTGACTCTCTAATTTTCTATTTT

TGGTAATAGGACATCTCCAAGTTTGCAGAGAAAGACAATATAGTTCTTgGAGAAGGT GGAAT C A

CACTGAGTGGAGGTCAACGAGCAAGAATTTCTTTAGCAAGGTGAATAACTAATTATTGGTCTAG

CAAGCATTTGCTGTAAATGTCATTCATGTAAAAAAATTACAGACATTTCTCTATTGCTTTATAT

TCTGTTTCTGGAATTGAAAAAATCCTGGGGTTTTATGGCTAGTGGGTTAAGAATCACATTTAAG

AACTATAAATAATGGTATAGTATCCAGATTTGGTAGAGATTATGGTTACTCAGAATCTGTGCCC

GTATCTTGGTGTCAGTGTATTTGTTTGCCTCATAGTATAGTTTACTACAAATGGAAAACTCTAG

GATTCTGCATAATACTGGACAGAGAAGATGTAAATATCTGTTAGTTCCATCATAGACCCTGCCA

CTCCAATGTACACACCAGCTTTAGGCTTCTTGGTATAGATAAACATACATTTTCAAAATTTTTC

ATCATAATTTTCATAACAAAATAGGAAGGCAAATGATGTCACTTGGCTTAAAATCTATAATATT

TAAAATAAACAGGACAAATGCATTAACATTGTTGGGGGAGGAGGTCCCTTAGTAGAAACACTCT

TGGTCCAAGCATTTTAAAGCTGTCAAAGAGATGTAAATATAGATAATGTATGTCAAGGAGAGAG

CTTTGTGGTTAAACTGTAACTTTCAGTTTAAACAATTATTGGTGACTCTGATGTCAAATGTTTC

TCAAGCTTTATCTGAACAAAATTCTTCTCACTTTGTTGCCAAAGTCGTTAACAAGAAATCACAT

TGACTCATTGATGTTTTGGCTCCTTTCCCTTACTTTCTGTTGCTTTCCAAAAGCTGAGACAGGA

AACTAACCCTAACTGAGCACCTGCAATTGCCTGGTAGTATTCTAGTCATGTGTGTACTTTTGTG

TGTATGTAATCCCCTTACAGCTCTGCAAAGTAAGAATTGTTCTCCCTGCTTTACAGAAGAGATC

ATAAGATAATTGAGGCTGTTAGATGTTAACTTGCCAAAAGCCATACAGGAAAATGGTAGAGTCA

CAGTTTGAACCAGGTCCTTTTGATTCTTTACATTAAACCATGCTTTGATCTTGGAAATACACTG

TAAGGCAATAAATCAATAGATACGGATAATTCACAGGCTTCTAAATAAATGGAAGTTGATTGTT

TTTATCTGTGAGCCAAAGTAAGACTTATTCTAA

(Template Construct 5; SEQ ID NO: 27274)

As described below in Table 49, shorter homology arms, e.g., 5' and/or 3' homology arms may be used. It is contemplated herein that one or both homology arms may be shortened to avoid including certain sequence repeat elements, e.g., Alu repeats, LINE elements. For example, a 5' homology arm may be shortened to avoid a sequence repeat element. In other embodiments, a 3' homology arm may be shortened to avoid a sequence repeat element. In some embodiments, both the 5' and the 3' homology arms may be shortened to avoid including certain sequence repeat elements.

In an embodiment, to correct G542X mutation in the CFTR gene, the 5' homology arm may be shortened less than 1000 nucleotides, e.g., e.g., 500 nucleotides, to avoid inclusion of a LINE repeat element in the 5' homology arm. The 5' homology arm is shown as bold sequence, the inserted base to correct the G542X mutation is shown as lower case sequence, and the 3' homology arm is shown as no emphasis capitalized sequence.

CCTGCAGGGGTGTGAATAATGTTCTTTTAGTTTCTCTTCTTAGGAGGTTTGTTCATTTTGGGAG

ATTTCTTTTGAAAAGAGTGAACTTAAATTGGAGAAAAGTACATTTTAGTATGTTGATAACATTT

GAATTTGTAAAATGGACCTATGGATGATCTACACATATTTATATACCCATAAATATACACATAT

TTTAATTTTTGGTATTTTATAATTATTATTTAATGATCATTCATGACATTTTAAAAATTACAGA

AAAATTTACATCTAAAATTTCAGCAATGTTGTTTTTGACCAACTAAATAAATTGCATTTGAAAT

AATGGAGATGCAATGTTCAAAATTTCAACTGTGGTTAAAGCAATAGTGTGATATATGATTACAT

TAGAAGGAAGATGTGCCTTTCAAATTCAGATTGAGCATACTAAAAGTGACTCTCTAATTTTCTA

TTTTTGGTAATAGGACATCTCCAAGTTTGCAGAGAAAGACAATATAGTTCTTgGAGAAGGTGGA

ATCACACTGAGTGGAGGTCAACGAGCAAGAAT T TCT T TAGCAAGGTGAATAACTAAT TAT TGGT

CTAGCAAGCAT T TGCTGTAAATGTCAT TCATGTAAAAAAAT TACAGACAT T TCTCTAT TGCT T T

ATAT TCTGT T TCTGGAAT TGAAAAAATCCTGGGGT T T TATGGCTAGTGGGT TAAGAATCACAT T

TAAGAACTATAAATAATGGTATAGTATCCAGAT T TGGTAGAGAT TATGGT TACTCAGAATCTGT

GCCCGTATCT TGGTGTCAGTGTAT T TGT T TGCCTCATAGTATAGT T TACTACAAATGGAAAACT

CTAGGAT TCTGCATAATACTGGACAGAGAAGATGTAAATATCTGT TAGT TCCATCATAGACCCT

GCCACTCCAATGTACACACCAGCT T TAGGCT TCT TGGTATAGATAAACATACAT T T TCAAAAT T

T T T CAT C AT AAT T T T C AT AAC AAAAT AGGAAGGC AAAT GAT

(Template Construct 6; SEQ ID NO: 27275)

It is contemplated herein that template nucleic acids for correcting a mutation may designed for use as a single- stranded oligonucleotide (ssODN). When using a ssODN, 5' and 3' homology arms may range up to about 200 base pairs (bp) in length, e.g., at least 25, 50, 75, 100, 125, 150, 175, or 200 bp in length. Longer homology arms are also contemplated for ssODNs as improvements in oligonucleotide synthesis continue to be made.

In an embodiment, an ssODN may be used to correct a mutation, e.g., G542X target site in the CFTR gene. For example, the ssODN may include 5' and 3' homology arms as shown below. The 5' homology arm is shown as bold sequence, the inserted bases to correct the G542X mutation is shown as lower case sequence, and the 3' homology arm is shown as no emphasis capitalized sequence.

AAAAGTGACTCTCTAATTTTCTATTTTTGGTAATAGGACATCTCCAAGTTTGCAGAGAAAGACA

ATATAGTTCTTgGAGAAGGTGGAATCACACTGAGTGGAGGTCAACGAGCAAGAAT T TCT T TAGC

AAGGTGAATAACTAAT TAT TGGT

(Template Construct 7; SEQ ID NO: 27276)

It is contemplated herein that, in an embodiment, a Cas9 molecule could potentially cleave donor constructs either prior to or following homology directed repair (e.g., homologous recombination), resulting in a possible non-homologous-end-joining event and further DNA sequence mutation at the chromosomal locus of interest. Therefore, to avoid cleavage of the donor sequence before and/or after Cas9-mediated homology directed repair, alternate versions of the donor sequence may be used where silent mutations are introduced. These silent mutations may disrupt Cas9 binding and cleavage, but not disrupt the amino acid sequence of the repaired gene. For example, mutations may include those made to a donor sequence to repair the CFTR gene, the mutant form which can cause CF or CF-like disease. In an embodiment, a silent mutation that disrupts Cas9 binding and cleavage, but does not disrupt the amino acid sequence of the repaired gene, is a sense mutation.

In an embodiment, to correct a mutation, e.g., G542X target site in the CFTR gene, and concomitantly introduce a silent mutation to disrupt subsequent Cas9 binding and cleavage, the homology arms, e.g., the 5' and 3' homology arms, may each comprise about 1000 base pairs (bp) of sequence flanking the most distal gRNAs (e.g., 1200bp of sequence on either side of the mutation). The 5' homology arm is shown as bold sequence, the inserted base to correct the G542X mutation is shown as lower case sequence, the silent sense mutation is shown as lower case underlined and italicized sequence, and the 3' homology arm is shown as no emphasis capitalized sequence. TGTCCATATGGTAGATAAATGGAACAAATGAATAACAGAAGTAACCATTTTGATACTTTAGATA TAGATAATATTGGATTATTTCTGGATTGTGAAAGAAGAAGGAAGAAGCATATGGAAGAGAAGTT TTAGTAGAGGGGAGGAAGGAGGAGGTGGAAACGAATGTACAAGGATGGGAGGAGAAAAGGGAGA GAGACTTTTTTTTTTTTAAGGCGAGAGTTTACTACCTATCTAACTCTTCGCATTCTTGAAGTCT CAGACCAAATCCCATCGGTTTGAAAGCCTCTAGGGTATTCTATCTATTGTATACTTCTGTTATG TACAAAATTAATTTGCCAATTAATTGTGAACTGTTTTATAAACTATCTTAAAATGGTTAGTTAA ATCTTTGGGATAGTATTTAGCTTTCTCCAGGATTATGACTTACCTTCTAAATTAGACATACAAT GCCTAGGAGTCAAGGACTATTTTGCATAAATTCCAGTCTTCTTTTACAATGCCTAGAATGATTG TTACCACAGAAATATTCATTACCTGGGAGAAAGGATGACAGGAGGGGCAGAATGAATGGAGAGA GGTCGTGAGAATGAGGTGCTGAGGATGGACGAGGAAGAAAGCTGTTTTAGTTGGGAGGATAGGT GACAGAAGCATGGAAAGGAATTGCCTTGGACCCATGGAAGCCCAGTGAAGATACTTAGATCCTG CAGGGGTGTGAATAATGTTCTTTTAGTTTCTCTTCTTAGGAGGTTTGTTCATTTTGGGAGATTT CTTTTGAAAAGAGTGAACTTAAATTGGAGAAAAGTACATTTTAGTATGTTGATAACATTTGAAT TTGTAAAATGGACCTATGGATGATCTACACATATTTATATACCCATAAATATACACATATTTTA ATTTTTGGTATTTTATAATTATTATTTAATGATCATTCATGACATTTTAAAAATTACAGAAAAA TTTACATCTAAAATTTCAGCAATGTTGTTTTTGACCAACTAAATAAATTGCATTTGAAATAATG GAGATGCAATGTTCAAAATTTCAACTGTGGTTAAAGCAATAGTGTGATATATGATTACATTAGA AGGAAGATGTGCCTTTCAAATTCAGATTGAGCATACTAAAAGTGACTCTCTAATTTTCTATTTT TGGTAATAGGACATCTCCAAGTTTGCAGAGAAAGACAATATAGTTCTagGtGAAGGTGGAATCA CACTGAGTGGAGGTCAACGAGCAAGAATTTCTTTAGCAAGGTGAATAACTAATTATTGGTCTAG CAAGCATTTGCTGTAAATGTCATTCATGTAAAAAAATTACAGACATTTCTCTATTGCTTTATAT TCTGTTTCTGGAATTGAAAAAATCCTGGGGTTTTATGGCTAGTGGGTTAAGAATCACATTTAAG AACTATAAATAATGGTATAGTATCCAGATTTGGTAGAGATTATGGTTACTCAGAATCTGTGCCC GTATCTTGGTGTCAGTGTATTTGTTTGCCTCATAGTATAGTTTACTACAAATGGAAAACTCTAG GATTCTGCATAATACTGGACAGAGAAGATGTAAATATCTGTTAGTTCCATCATAGACCCTGCCA CTCCAATGTACACACCAGCTTTAGGCTTCTTGGTATAGATAAACATACATTTTCAAAATTTTTC ATCATAATTTTCATAACAAAATAGGAAGGCAAATGATGTCACTTGGCTTAAAATCTATAATATT TAAAATAAACAGGACAAATGCATTAACATTGTTGGGGGAGGAGGTCCCTTAGTAGAAACACTCT TGGTCCAAGCATTTTAAAGCTGTCAAAGAGATGTAAATATAGATAATGTATGTCAAGGAGAGAG CTTTGTGGTTAAACTGTAACTTTCAGTTTAAACAATTATTGGTGACTCTGATGTCAAATGTTTC TCAAGCTTTATCTGAACAAAATTCTTCTCACTTTGTTGCCAAAGTCGTTAACAAGAAATCACAT TGACTCATTGATGTTTTGGCTCCTTTCCCTTACTTTCTGTTGCTTTCCAAAAGCTGAGACAGGA AACTAACCCTAACTGAGCACCTGCAATTGCCTGGTAGTATTCTAGTCATGTGTGTACTTTTGTG

TGTATGTAATCCCCTTACAGCTCTGCAAAGTAAGAATTGTTCTCCCTGCTTTACAGAAGAGATC

ATAAGATAATTGAGGCTGTTAGATGTTAACTTGCCAAAAGCCATACAGGAAAATGGTAGAGTCA

CAGTTTGAACCAGGTCCTTTTGATTCTTTACATTAAACCATGCTTTGATCTTGGAAATACACTG

TAAGGCAATAAATCAATAGATACGGATAATTCACAGGCTTCTAAATAAATGGAAGTTGATTGTT

TTTATCTGTGAGCCAAAGTAAGACTTATTCTAA

(Template Construct 8; SEQ ID NO: 27277)

In an embodiment, to correct a mutation, e.g., G542X target site in the CFTR gene, and concomitantly introduce a silent mutation to disrupt subsequent Cas9 binding and cleavage, the 5' homology arm may be shortened less than 750 nucleotides, e.g., 500 nucleotides, to avoid inclusion of a LINE repeat element in the 5' homology arm. The 5' homology arm is shown as bold sequence, the inserted base to correct the G542X mutation is shown as lower case sequence, the silent sense mutation is shown as lower case underlined and italicized sequence, and the 3' homology arm is shown as no emphasis capitalized sequence.

CCTGCAGGGGTGTGAATAATGTTCTTTTAGTTTCTCTTCTTAGGAGGTTTGTTCATTTTGGGAG

ATTTCTTTTGAAAAGAGTGAACTTAAATTGGAGAAAAGTACATTTTAGTATGTTGATAACATTT

GAATTTGTAAAATGGACCTATGGATGATCTACACATATTTATATACCCATAAATATACACATAT

TTTAATTTTTGGTATTTTATAATTATTATTTAATGATCATTCATGACATTTTAAAAATTACAGA

AAAATTTACATCTAAAATTTCAGCAATGTTGTTTTTGACCAACTAAATAAATTGCATTTGAAAT

AATGGAGATGCAATGTTCAAAATTTCAACTGTGGTTAAAGCAATAGTGTGATATATGATTACAT

TAGAAGGAAGATGTGCCTTTCAAATTCAGATTGAGCATACTAAAAGTGACTCTCTAATTTTCTA

TTTTTGGTAATAGGACATCTCCAAGTTTGCAGAGAAAGACAATATAGTTCTagGtGAAGGTGGA

ATCACACTGAGTGGAGGTCAACGAGCAAGAATTTCTTTAGCAAGGTGAATAACTAATTATTGGT

CTAGCAAGCATTTGCTGTAAATGTCATTCATGTAAAAAAATTACAGACATTTCTCTATTGCTTT

ATATTCTGTTTCTGGAATTGAAAAAATCCTGGGGTTTTATGGCTAGTGGGTTAAGAATCACATT

TAAGAACTATAAATAATGGTATAGTATCCAGATTTGGTAGAGATTATGGTTACTCAGAATCTGT

GCCCGTATCTTGGTGTCAGTGTATTTGTTTGCCTCATAGTATAGTTTACTACAAATGGAAAACT

CTAGGATTCTGCATAATACTGGACAGAGAAGATGTAAATATCTGTTAGTTCCATCATAGACCCT

GCCACTCCAATGTACACACCAGCTTTAGGCTTCTTGGTATAGATAAACATACATTTTCAAAATT

T T T CAT C AT AAT T T T C AT AAC AAAAT AGGAAGGC AAAT GAT

(Template Construct 9; SEQ ID NO: 27278) In an embodiment, an ssODN may be to correct a mutation, e.g., G542X target site in the CFTR gene, and concomitantly introduce a silent mutation to disrupt subsequent Cas9 binding and cleavage. For example, the ssODN may include 5' and 3' homology arms as shown below. The 5' homology arm is shown as bold sequence, the inserted base to correct the G542X mutation is shown as lower case sequence, the silent sense mutation is shown as lower case underlined and italicized sequence, and the 3' homology arm is shown as no emphasis capitalized sequence.

AAAAGTGACTCTCTAATTTTCTATTTTTGGTAATAGGACATCTCCAAGTTTGCAGAGAAAGACA

ATATAGTTCTagGtGAAGGTGGAATCACACTGAGTGGAGGTCAACGAGCAAGAATTTCTTTAGC

AAGGTGAATAACTAATTATTGGT

(Template Construct 10; SEQ ID NO: 27279)

The underlined A has been changed from a T to A at that position and the underlined T has been changed from an A to T at that position so that wild-type CFTR is still transcribed, but the PAM sequence AGG has been modified to reduce or eliminate Cas9 cleavage at that locus.

Exemplary template nucleic acids (also referred to herein as donor constructs) to correction a mutation, e.g., G551D target site in the CFTR gene, are provided.

Suitable sequence for the 5' homology arm can be selected from (e.g., includes a portion of) or include the following sequence:

TGAATAACAGAAGTAACCATTTTGATACTTTAGATATAGATAATATTGGATTATTTCTGGATTG TGAAAGAAGAAGGAAGAAGCATATGGAAGAGAAGTTTTAGTAGAGGGGAGGAAGGAGGAGGTGG AAACGAAT GT AC AAGGAT GGGAGGAGAAAAGGGAGAGAGAC TTTTTTTTTTT T AAGGCGAGAGT TTACTACCTATCTAACTCTTCGCATTCTTGAAGTCTCAGACCAAATCCCATCGGTTTGAAAGCC TCTAGGGTATTCTATCTATTGTATACTTCTGTTATGTACAAAATTAATTTGCCAATTAATTGTG AACTGTTTTATAAACTATCTTAAAATGGTTAGTTAAATCTTTGGGATAGTATTTAGCTTTCTCC AGGATTATGACTTACCTTCTAAATTAGACATACAATGCCTAGGAGTCAAGGACTATTTTGCATA AATTCCAGTCTTCTTTTACAATGCCTAGAATGATTGTTACCACAGAAATATTCATTACCTGGGA GAAAGGATGACAGGAGGGGCAGAATGAATGGAGAGAGGTCGTGAGAATGAGGTGCTGAGGATGG ACGAGGAAGAAAGCTGTTTTAGTTGGGAGGATAGGTGACAGAAGCATGGAAAGGAATTGCCTTG GACCCATGGAAGCCCAGTGAAGATACTTAGATCCTGCAGGGGTGTGAATAATGTTCTTTTAGTT TCTCTTCTTAGGAGGTTTGTTCATTTTGGGAGATTTCTTTTGAAAAGAGTGAACTTAAATTGGA GAAAAGTACATTTTAGTATGTTGATAACATTTGAATTTGTAAAATGGACCTATGGATGATCTAC ACATATTTATATACCCATAAATATACACATATTTTAATTTTTGGTATTTTATAATTATTATTTA

ATGATCATTCATGACATTTTAAAAATTACAGAAAAATTTACATCTAAAATTTCAGCAATGTTGT

TTTTGACCAACTAAATAAATTGCATTTGAAATAATGGAGATGCAATGTTCAAAATTTCAACTGT

GGTTAAAGCAATAGTGTGATATATGATTACATTAGAAGGAAGATGTGCCTTTCAAATTCAGATT

GAGCATACTAAAAGTGACTCTCTAATTTTCTATTTTTGGTAATAGGACATCTCCAAGTTTGCAG

AGAAAGAC AAT AT AGT T C T T GGAGAAGGT GGAAT C AC AC T GAGTGGAG

SEQ ID NO: 27280 (5Ή arm)

Suitable sequence for the 3' homology arm can be selected from (e.g., includes a portion of) or include the following sequence:

TCAACGAGCAAGAATTTCTTTAGCAAGGTGAATAACTAATTATTGGTCTAGCAAGCATTTGCTG

TAAATGTCATTCATGTAAAAAAATTACAGACATTTCTCTATTGCTTTATATTCTGTTTCTGGAA

TTGAAAAAATCCTGGGGTTTTATGGCTAGTGGGTTAAGAATCACATTTAAGAACTATAAATAAT

GGTATAGTATCCAGATTTGGTAGAGATTATGGTTACTCAGAATCTGTGCCCGTATCTTGGTGTC

AGTGTATTTGTTTGCCTCATAGTATAGTTTACTACAAATGGAAAACTCTAGGATTCTGCATAAT

ACTGGACAGAGAAGATGTAAATATCTGTTAGTTCCATCATAGACCCTGCCACTCCAATGTACAC

ACCAGCTTTAGGCTTCTTGGTATAGATAAACATACATTTTCAAAATTTTTCATCATAATTTTCA

TAACAAAATAGGAAGGCAAATGATGTCACTTGGCTTAAAATCTATAATATTTAAAATAAACAGG

ACAAATGCATTAACATTGTTGGGGGAGGAGGTCCCTTAGTAGAAACACTCTTGGTCCAAGCATT

TTAAAGCTGTCAAAGAGATGTAAATATAGATAATGTATGTCAAGGAGAGAGCTTTGTGGTTAAA

CTGTAACTTTCAGTTTAAACAATTATTGGTGACTCTGATGTCAAATGTTTCTCAAGCTTTATCT

GAACAAAATTCTTCTCACTTTGTTGCCAAAGTCGTTAACAAGAAATCACATTGACTCATTGATG

TTTTGGCTCCTTTCCCTTACTTTCTGTTGCTTTCCAAAAGCTGAGACAGGAAACTAACCCTAAC

TGAGCACCTGCAATTGCCTGGTAGTATTCTAGTCATGTGTGTACTTTTGTGTGTATGTAATCCC

CTTACAGCTCTGCAAAGTAAGAATTGTTCTCCCTGCTTTACAGAAGAGATCATAAGATAATTGA

GGCTGTTAGATGTTAACTTGCCAAAAGCCATACAGGAAAATGGTAGAGTCACAGTTTGAACCAG

GTCCTTTTGATTCTTTACATTAAACCATGCTTTGATCTTGGAAATACACTGTAAGGCAATAAAT

CAATAGATACGGATAATTCACAGGCTTCTAAATAAATGGAAGTTGATTGTTTTTATCTGTGAGC

C AAAGT AAGAC T T AT T CTAAGAAT T CC AC AAAT T T AGAT AAGAT AGAG

SEQ ID NO: 27281 (3Ή arm)

In an embodiment, the replacement sequence comprises or consists of a Guanine (G) residue. In an embodiment, to correct a mutation, e.g., G551D target site in the CFTR gene, the homology arms, e.g., the 5' and 3' homology arms, may each comprise about 1000 base pairs (bp) of sequence flanking the most distal gRNAs (e.g., 1200bp of sequence on either side of the mutation). The 5' homology arm is shown as bold sequence, codon 551 is shown as underlined sequence, the inserted base to correct the G551D mutation is shown as non-bold and boxed sequence, and the 3' homology arm is shown as no emphasis sequence.

TGAATAACAGAAGTAACCATTTTGATACTTTAGATATAGATAATATTGGATTATTTCTGGATTG TGAAAGAAGAAGGAAGAAGCATATGGAAGAGAAGTTTTAGTAGAGGGGAGGAAGGAGGAGGTGG AAACGAATGTACAAGGATGGGAGGAGAAAAGGGAGAGAGACTTTTTTTTTTTTAAGGCGAGAGT TTACTACCTATCTAACTCTTCGCATTCTTGAAGTCTCAGACCAAATCCCATCGGTTTGAAAGCC TCTAGGGTATTCTATCTATTGTATACTTCTGTTATGTACAAAATTAATTTGCCAATTAATTGTG AACTGTTTTATAAACTATCTTAAAATGGTTAGTTAAATCTTTGGGATAGTATTTAGCTTTCTCC AGGATTATGACTTACCTTCTAAATTAGACATACAATGCCTAGGAGTCAAGGACTATTTTGCATA AATTCCAGTCTTCTTTTACAATGCCTAGAATGATTGTTACCACAGAAATATTCATTACCTGGGA GAAAGGATGACAGGAGGGGCAGAATGAATGGAGAGAGGTCGTGAGAATGAGGTGCTGAGGATGG ACGAGGAAGAAAGCTGTTTTAGTTGGGAGGATAGGTGACAGAAGCATGGAAAGGAATTGCCTTG GACCCATGGAAGCCCAGTGAAGATACTTAGATCCTGCAGGGGTGTGAATAATGTTCTTTTAGTT TCTCTTCTTAGGAGGTTTGTTCATTTTGGGAGATTTCTTTTGAAAAGAGTGAACTTAAATTGGA GAAAAGTACATTTTAGTATGTTGATAACATTTGAATTTGTAAAATGGACCTATGGATGATCTAC ACATATTTATATACCCATAAATATACACATATTTTAATTTTTGGTATTTTATAATTATTATTTA

ATGATCATTCATGACATTTTAAAAATTACAGAAAAATTTACATCTAAAATTTCAGCAATGTTGT TTTTGACCAACTAAATAAATTGCATTTGAAATAATGGAGATGCAATGTTCAAAATTTCAACTGT GGTTAAAGCAATAGTGTGATATATGATTACATTAGAAGGAAGATGTGCCTTTCAAATTCAGATT GAGCATACTAAAAGTGACTCTCTAATTTTCTATTTTTGGTAATAGGACATCTCCAAGTTTGCAG

AGAAAGACAATATAGTTCTTGGAGAAGGTGGAATCACACTGAGTGGAG[G|TCAACGAGCAAGAAT

T TCT T TAGCAAGGTGAATAACTAAT TAT TGGTCTAGCAAGCAT T TGCTGTAAATGTCAT TCATG TAAAAAAAT TACAGACAT T TCTCTAT TGCT T TATAT TCTGT T TCTGGAAT TGAAAAAATCCTGG GGT T T TATGGCTAGTGGGT TAAGAATCACAT T TAAGAACTATAAATAATGGTATAGTATCCAGA T T TGGTAGAGAT TATGGT TACTCAGAATCTGTGCCCGTATCT TGGTGTCAGTGTAT T TGT T TGC CTCATAGTATAGT T TACTACAAATGGAAAACTCTAGGAT TCTGCATAATACTGGACAGAGAAGA TGTAAATATCTGT TAGT TCCATCATAGACCCTGCCACTCCAATGTACACACCAGCT T TAGGCT T CTTGGTATAGATAAACATACATTTTCAAAATTTTTCATCATAATTTTCATAACAAAATAGGAAG

GCAAATGATGTCACTTGGCTTAAAATCTATAATATTTAAAATAAACAGGACAAATGCATTAACA

TTGTTGGGGGAGGAGGTCCCTTAGTAGAAACACTCTTGGTCCAAGCATTTTAAAGCTGTCAAAG

AGATGTAAATATAGATAATGTATGTCAAGGAGAGAGCTTTGTGGTTAAACTGTAACTTTCAGTT

TAAACAATTATTGGTGACTCTGATGTCAAATGTTTCTCAAGCTTTATCTGAACAAAATTCTTCT

CACTTTGTTGCCAAAGTCGTTAACAAGAAATCACATTGACTCATTGATGTTTTGGCTCCTTTCC

CTTACTTTCTGTTGCTTTCCAAAAGCTGAGACAGGAAACTAACCCTAACTGAGCACCTGCAATT

GCCTGGTAGTATTCTAGTCATGTGTGTACTTTTGTGTGTATGTAATCCCCTTACAGCTCTGCAA

AGTAAGAATTGTTCTCCCTGCTTTACAGAAGAGATCATAAGATAATTGAGGCTGTTAGATGTTA

ACTTGCCAAAAGCCATACAGGAAAATGGTAGAGTCACAGTTTGAACCAGGTCCTTTTGATTCTT

TACATTAAACCATGCTTTGATCTTGGAAATACACTGTAAGGCAATAAATCAATAGATACGGATA

ATTCACAGGCTTCTAAATAAATGGAAGTTGATTGTTTTTATCTGTGAGCCAAAGTAAGACTTAT

TCTAAGAATTCCACAAATTTAGATAAGATAGAG

(Template Construct 11; SEQ ID NO: 27282)

As described below in Table 49, shorter homology arms, e.g., 5' and/or 3' homology arms may be used.

It is contemplated herein that one or both homology arms may be shortened to avoid including certain sequence repeat elements, e.g., Alu repeats, LINE elements. For example, a 5' homology arm may be shortened to avoid a sequence repeat element. In other embodiments, a 3' homology arm may be shortened to avoid a sequence repeat element. In some embodiments, both the 5' and the 3' homology arms may be shortened to avoid including certain sequence repeat elements.

In an embodiment, to correct G551D mutation in the CFTR gene, the 5' homology arm may be shortened less than 1000 nucleotides, e.g., approximately 750 nucleotides, e.g., 724 nucleotides, to avoid inclusion of a LINE repeat element in the 5' homology arm. The 5' homology arm is shown as bold sequence, codon 551 is shown as underlined sequence, the inserted base to correct the G551D mutation is shown as non-bold and boxed sequence, and the 3' homology arm is shown as no emphasis sequence.

AATGATTGTTACCACAGAAATATTCATTACCTGGGAGAAAGGATGACAGGAGGGGCAGAATGAA TGGAGAGAGGTCGTGAGAATGAGGTGCTGAGGATGGACGAGGAAGAAAGCTGTTTTAGTTGGGA GGATAGGTGACAGAAGCATGGAAAGGAATTGCCTTGGACCCATGGAAGCCCAGTGAAGATACTT AGATCCTGCAGGGGTGTGAATAATGTTCTTTTAGTTTCTCTTCTTAGGAGGTTTGTTCATTTTG GGAGATTTCTTTTGAAAAGAGTGAACTTAAATTGGAGAAAAGTACATTTTAGTATGTTGATAAC ATTTGAATTTGTAAAATGGACCTATGGATGATCTACACATATTTATATACCCATAAATATACAC ATATTTTAATTTTTGGTATTTTATAATTATTATTTAATGATCATTCATGACATTTTAAAAATTA

CAGAAAAATTTACATCTAAAATTTCAGCAATGTTGTTTTTGACCAACTAAATAAATTGCATTTG AAATAATGGAGATGCAATGTTCAAAATTTCAACTGTGGTTAAAGCAATAGTGTGATATATGATT ACATTAGAAGGAAGATGTGCCTTTCAAATTCAGATTGAGCATACTAAAAGTGACTCTCTAATTT TCTATTTTTGGTAATAGGACATCTCCAAGTTTGCAGAGAAAGACAATATAGTTCTTGGAGAAGG

TGGAATCACACTGAGTGGAG[G|TCAACGAGCAAGAAT T T C T T T AGC AAGGT GAAT AAC T AAT TAT TGGTCTAGCAAGCATTTGCTGTAAATGTCATTCATGTAAAAAAATTACAGACATTTCTCTATTG CTTTATATTCTGTTTCTGGAATTGAAAAAATCCTGGGGTTTTATGGCTAGTGGGTTAAGAATCA CATTTAAGAACTATAAATAATGGTATAGTATCCAGATTTGGTAGAGATTATGGTTACTCAGAAT CTGTGCCCGTATCTTGGTGTCAGTGTATTTGTTTGCCTCATAGTATAGTTTACTACAAATGGAA AACTCTAGGATTCTGCATAATACTGGACAGAGAAGATGTAAATATCTGTTAGTTCCATCATAGA CCCTGCCACTCCAATGTACACACCAGCTTTAGGCTTCTTGGTATAGATAAACATACATTTTCAA AATTTTTCATCATAATTTTCATAACAAAATAGGAAGGCAAATGATGTCACTTGGCTTAAAATCT ATAATATTTAAAATAAACAGGACAAATGCATTAACATTGTTGGGGGAGGAGGTCCCTTAGTAGA AACACTCTTGGTCCAAGCATTTTAAAGCTGTCAAAGAGATGTAAATATAGATAATGTATGTCAA GGAGAGAGCTTTGTGGTTAAACTGTAACTTTCAGTTTAAACAATTATTGGTGACTCTGATGTCA AATGTTTCTCAAGCTTTATCTGAACAAAATTCTTCTCACTTTGTTGCCAAAGTCGTTAACAAGA AATCACATTGACTCATTGATGTTTTGGCTCCTTTCCCTTACTTTCTGTTGCTTTCCAAAAGCTG AGACAGGA

(Template Construct 12; SEQ ID NO: 27283)

In an embodiment, to correct G551D mutation in the CFTR gene, the 5' homology arm may be shortened less than 750 nucleotides, e.g., e.g., 500 nucleotides, to avoid inclusion of a LINE repeat element in the 5' homology arm. The 5' homology arm is shown as bold sequence, the inserted base to correct the G551D mutation is shown as lower case sequence, and the 3' homology arm is shown as no emphasis capitalized sequence.

AGTTTCTCTTCTTAGGAGGTTTGTTCATTTTGGGAGATTTCTTTTGAAAAGAGTGAACTTAAAT TGGAGAAAAGTACATTTTAGTATGTTGATAACATTTGAATTTGTAAAATGGACCTATGGATGAT CTACACATATTTATATACCCATAAATATACACATATTTTAATTTTTGGTATTTTATAATTATTA TTTAATGATCATTCATGACATTTTAAAAATTACAGAAAAATTTACATCTAAAATTTCAGCAATG

TTGTTTTTGACCAACTAAATAAATTGCATTTGAAATAATGGAGATGCAATGTTCAAAATTTCAA

CTGTGGTTAAAGCAATAGTGTGATATATGATTACATTAGAAGGAAGATGTGCCTTTCAAATTCA

GATTGAGCATACTAAAAGTGACTCTCTAATTTTCTATTTTTGGTAATAGGACATCTCCAAGTTT

GCAGAGAAAGACAATATAGTTCTTGGAGAAGGTGGAATCACACTGAGTGGAGgTCAACGAGCAA

GAATTTCTTTAGCAAGGTGAATAACTAATTATTGGTCTAGCAAGCATTTGCTGTAAATGTCATT

CATGTAAAAAAATTACAGACATTTCTCTATTGCTTTATATTCTGTTTCTGGAATTGAAAAAATC

CTGGGGTTTTATGGCTAGTGGGTTAAGAATCACATTTAAGAACTATAAATAATGGTATAGTATC

CAGATTTGGTAGAGATTATGGTTACTCAGAATCTGTGCCCGTATCTTGGTGTCAGTGTATTTGT

TTGCCTCATAGTATAGTTTACTACAAATGGAAAACTCTAGGATTCTGCATAATACTGGACAGAG

AAGATGTAAATATCTGTTAGTTCCATCATAGACCCTGCCACTCCAATGTACACACCAGCTTTAG

GCTTCTTGGTATAGATAAACATACATTTTCAAAATTTTTCATCATAATTTTCATAACAAAATAG

GAAGGCAAATGATGTCACTTGGCTTAAAATCTATAATATTT

(Template Construct 13; SEQ ID NO: 27284)

It is contemplated herein that template nucleic acids for correcting a mutation may designed for use as a single- stranded oligonucleotide (ssODN). When using a ssODN, 5' and 3' homology arms may range up to about 200 base pairs (bp) in length, e.g., at least 25, 50, 75, 100, 125, 150, 175, or 200 bp in length. Longer homology arms are also contemplated for ssODNs as improvements in oligonucleotide synthesis continue to be made.

In an embodiment, an ssODN may be used to correct a mutation, e.g., G551D target site in the CFTR gene. For example, the ssODN may include 5' and 3' homology arms as shown below. The 5' homology arm is shown as bold sequence, the inserted bases to correct the G542X mutation is shown as lower case sequence, and the 3' homology arm is shown as no emphasis capitalized sequence.

GGTAATAGGACATCTCCAAGTTTGCAGAGAAAGACAATATAGTTCTTGGAGAAGGTGGAATCAC

ACTGAGTGGAGgTCAACGAGCAAGAATTTCTTTAGCAAGGTGAATAACTAATTATTGGTCTAGC

AAGCATTTGCTGTAAATGTCATT

(Template Construct 14; SEQ ID NO: 27285)

In an embodiment, to correct a mutation, e.g., G551D target site in the CFTR gene, and concomitantly introduce a silent mutation to disrupt subsequent Cas9 binding and cleavage, the homology arms, e.g., the 5' and 3' homology arms, may each comprise about 1000 base pairs (bp) of sequence flanking the most distal gRNAs (e.g., 1200bp of sequence on either side of the mutation). The 5' homology arm is shown as bold sequence, the inserted base to correct the G551D mutation is shown as lower case sequence, the silent sense mutation is shown as lower case underlined and italicized sequence, and the 3' homology arm is shown as no emphasis capitalized sequence.

TGAATAACAGAAGTAACCATTTTGATACTTTAGATATAGATAATATTGGATTATTTCTGGATTG TGAAAGAAGAAGGAAGAAGCATATGGAAGAGAAGTTTTAGTAGAGGGGAGGAAGGAGGAGGTGG AAACGAATGTACAAGGATGGGAGGAGAAAAGGGAGAGAGACTTTTTTTTTTTTAAGGCGAGAGT TTACTACCTATCTAACTCTTCGCATTCTTGAAGTCTCAGACCAAATCCCATCGGTTTGAAAGCC TCTAGGGTATTCTATCTATTGTATACTTCTGTTATGTACAAAATTAATTTGCCAATTAATTGTG AACTGTTTTATAAACTATCTTAAAATGGTTAGTTAAATCTTTGGGATAGTATTTAGCTTTCTCC AGGATTATGACTTACCTTCTAAATTAGACATACAATGCCTAGGAGTCAAGGACTATTTTGCATA AATTCCAGTCTTCTTTTACAATGCCTAGAATGATTGTTACCACAGAAATATTCATTACCTGGGA GAAAGGATGACAGGAGGGGCAGAATGAATGGAGAGAGGTCGTGAGAATGAGGTGCTGAGGATGG ACGAGGAAGAAAGCTGTTTTAGTTGGGAGGATAGGTGACAGAAGCATGGAAAGGAATTGCCTTG GACCCATGGAAGCCCAGTGAAGATACTTAGATCCTGCAGGGGTGTGAATAATGTTCTTTTAGTT TCTCTTCTTAGGAGGTTTGTTCATTTTGGGAGATTTCTTTTGAAAAGAGTGAACTTAAATTGGA GAAAAGTACATTTTAGTATGTTGATAACATTTGAATTTGTAAAATGGACCTATGGATGATCTAC ACATATTTATATACCCATAAATATACACATATTTTAATTTTTGGTATTTTATAATTATTATTTA ATGATCATTCATGACATTTTAAAAATTACAGAAAAATTTACATCTAAAATTTCAGCAATGTTGT TTTTGACCAACTAAATAAATTGCATTTGAAATAATGGAGATGCAATGTTCAAAATTTCAACTGT GGTTAAAGCAATAGTGTGATATATGATTACATTAGAAGGAAGATGTGCCTTTCAAATTCAGATT GAGCATACTAAAAGTGACTCTCTAATTTTCTATTTTTGGTAATAGGACATCTCCAAGTTTGCAG AGAAAGACAATATAGTTCTTGGAGAAGGTGGAATCACACTGtcTGGAGgTCAACGAGCAAGAAT TTCTTTAGCAAGGTGAATAACTAATTATTGGTCTAGCAAGCATTTGCTGTAAATGTCATTCATG TAAAAAAATTACAGACATTTCTCTATTGCTTTATATTCTGTTTCTGGAATTGAAAAAATCCTGG GGTTTTATGGCTAGTGGGTTAAGAATCACATTTAAGAACTATAAATAATGGTATAGTATCCAGA TTTGGTAGAGATTATGGTTACTCAGAATCTGTGCCCGTATCTTGGTGTCAGTGTATTTGTTTGC CTCATAGTATAGTTTACTACAAATGGAAAACTCTAGGATTCTGCATAATACTGGACAGAGAAGA TGTAAATATCTGTTAGTTCCATCATAGACCCTGCCACTCCAATGTACACACCAGCTTTAGGCTT CTTGGTATAGATAAACATACATTTTCAAAATTTTTCATCATAATTTTCATAACAAAATAGGAAG GCAAATGATGTCACTTGGCTTAAAATCTATAATATTTAAAATAAACAGGACAAATGCATTAACA TTGTTGGGGGAGGAGGTCCCTTAGTAGAAACACTCTTGGTCCAAGCATTTTAAAGCTGTCAAAG

AGATGTAAATATAGATAATGTATGTCAAGGAGAGAGCTTTGTGGTTAAACTGTAACTTTCAGTT

TAAACAATTATTGGTGACTCTGATGTCAAATGTTTCTCAAGCTTTATCTGAACAAAATTCTTCT

CACTTTGTTGCCAAAGTCGTTAACAAGAAATCACATTGACTCATTGATGTTTTGGCTCCTTTCC

CTTACTTTCTGTTGCTTTCCAAAAGCTGAGACAGGAAACTAACCCTAACTGAGCACCTGCAATT

GCCTGGTAGTATTCTAGTCATGTGTGTACTTTTGTGTGTATGTAATCCCCTTACAGCTCTGCAA

AGTAAGAATTGTTCTCCCTGCTTTACAGAAGAGATCATAAGATAATTGAGGCTGTTAGATGTTA

ACTTGCCAAAAGCCATACAGGAAAATGGTAGAGTCACAGTTTGAACCAGGTCCTTTTGATTCTT

TACATTAAACCATGCTTTGATCTTGGAAATACACTGTAAGGCAATAAATCAATAGATACGGATA

ATTCACAGGCTTCTAAATAAATGGAAGTTGATTGTTTTTATCTGTGAGCCAAAGTAAGACTTAT

TCTAAGAATTCCACAAATTTAGATAAGATAGAG

(Template Construct 15; SEQ ID NO: 27286)

In an embodiment, to correct a mutation, e.g., G551D target site in the CFTR gene, and concomitantly introduce a silent mutation to disrupt subsequent Cas9 binding and cleavage, the 5' homology arm may be shortened less than 750 nucleotides, e.g., 500 nucleotides, to avoid inclusion of a LINE repeat element in the 5' homology arm. The 5' homology arm is shown as bold sequence, the inserted base to correct the G551D mutation is shown as lower case sequence, the silent sense mutation is shown as lower case underlined and italicized sequence, and the 3' homology arm is shown as no emphasis capitalized sequence.

AGTTTCTCTTCTTAGGAGGTTTGTTCATTTTGGGAGATTTCTTTTGAAAAGAGTGAACTTAAAT TGGAGAAAAGTACATTTTAGTATGTTGATAACATTTGAATTTGTAAAATGGACCTATGGATGAT CTACACATATTTATATACCCATAAATATACACATATTTTAATTTTTGGTATTTTATAATTATTA TTTAATGATCATTCATGACATTTTAAAAATTACAGAAAAATTTACATCTAAAATTTCAGCAATG TTGTTTTTGACCAACTAAATAAATTGCATTTGAAATAATGGAGATGCAATGTTCAAAATTTCAA CTGTGGTTAAAGCAATAGTGTGATATATGATTACATTAGAAGGAAGATGTGCCTTTCAAATTCA GATTGAGCATACTAAAAGTGACTCTCTAATTTTCTATTTTTGGTAATAGGACATCTCCAAGTTT GCAGAGAAAGACAATATAGTTCTTGGAGAAGGTGGAATCACACTGtcTGGAGgTCAACGAGCAA GAATTTCTTTAGCAAGGTGAATAACTAATTATTGGTCTAGCAAGCATTTGCTGTAAATGTCATT CATGTAAAAAAATTACAGACATTTCTCTATTGCTTTATATTCTGTTTCTGGAATTGAAAAAATC CTGGGGTTTTATGGCTAGTGGGTTAAGAATCACATTTAAGAACTATAAATAATGGTATAGTATC CAGATTTGGTAGAGATTATGGTTACTCAGAATCTGTGCCCGTATCTTGGTGTCAGTGTATTTGT TTGCCTCATAGTATAGTTTACTACAAATGGAAAACTCTAGGATTCTGCATAATACTGGACAGAG

AAGATGTAAATATCTGTTAGTTCCATCATAGACCCTGCCACTCCAATGTACACACCAGCTTTAG

GCTTCTTGGTATAGATAAACATACATTTTCAAAATTTTTCATCATAATTTTCATAACAAAATAG

GAAGGCAAATGATGTCACTTGGCTTAAAATCTATAATATTT

(Template Construct 16; SEQ ID NO: 27287)

In an embodiment, an ssODN may be to correct a mutation, e.g., G551D target site in the CFTR gene, and concomitantly introduce a silent mutation to disrupt subsequent Cas9 binding and cleavage. For example, the ssODN may include 5' and 3' homology arms as shown below. The 5' homology arm is shown as bold sequence, the inserted base to correct the G551D mutation is shown as lower case sequence, the silent sense mutation is shown as lower case underlined and italicized sequence, and the 3' homology arm is shown as no emphasis capitalized sequence.

GGTAATAGGACATCTCCAAGTTTGCAGAGAAAGACAATATAGTTCTTGGAGAAGGTGGAATCAC ACTGtcTGGAGgTCAACGAGCAAGAATTTCTTTAGCAAGGTGAATAACTAATTATTGGTCTAGC AAGCATTTGCTGTAAATGTCATT

(Template Construct 18; SEQ ID NO: 27288)

The underlined T has been changed from a A to T at that position and the underlined C has been changed from an G to C at that position so that wild-type CFTR is still transcribed, but the PAM sequence TGG has been modified to reduce or eliminate Cas9 cleavage at that locus.

Exemplary template nucleic acids (also referred to herein as donor constructs) to correction a mutation, e.g., N1303K target site in the CFTR gene, are provided.

Suitable sequence for the 5' homology arm can be selected from (e.g., includes a portion of) or include the following sequence:

GTTTCTGAGACATTTGACAACAACTTTTTCTTTAAGTCATCAGTTATGCCCCGGGGTATGAAAT TTCTAACATGATCCTCAGTAAACTTGGCTGCCTTGCTGAGGATACTCTCCATCTGCCTGAGAGA CACAGACACCATTAATTGGGAATTGACTTGACTTGTGTGGTTCCTTGTGGACCAGATGGCCACT AAATATTCTCATTTCAAGGCAATTGGTAAAAACTACACTTCAAGAAATTTCATTCTTAATTCCC CTTAGTGGATGTTATTAACCAAAGGCAAAAGAAAAAAAGGGTAAAAAAAATATTCTAAATGTTA ATATCAAAAATATTATTTTCAATTCACCCCAGGCACAGAGAACTAAGTATTATTATTGCTATTG CACCGGCATTCCCCAATGAGACAGTGATTTTCTTTTAAGACATTTTTAAATAATATAGGCAGAA TTAAGTAGACGGTGATCTGGTAAGTAGATGTTTCAGGGTAACAGCTGTGCAATGCTCCATGCAG GGAATTAGATTGTCATTTTATTCCTTACCAGGAACATACATTCAGTTAAACAATTATTTGACTT

CTGCTCTTCCACTGATTTCTAAGTTGAGGCTCTCTCTTGTGCCTGTCTGATCAGATAAGTAGAG

TTGTGCCTTGGTTTATAGATGAGATAAATGTGTATTTGAATAAGCATAAGTTAAAGAAATTTTA

AAATCCCTTAGGAAGCTAGGCTTATCAGAGAAATCCAAGGAAATACATTAACAAACTAGGAATT

TGTTCTAACAGGTTAATTATAACTCATAAACTTATTGGGTTTTTTTACCTTTTAATTTTATATT

ACATTTGCTTATAATAAGGAATATTGCTAGGAATAAAATTTTTTAATATTCTACAATTAACAAT

TATCTCAATTTCTTTATTCTAAAGACATTGGGATTAGAAAAATGTTCACAAGGGACTCCAAATA

TTGCTGTAGTATTTGTTTCTTAAAAGAATGATACAAAGCAGACATGATAAAATATTAAAATTTG

AGAGAACTTGATGGTAAGTACATGGGTGTTTCTTATTTTAAAATAATTTTTCTACTTGAAATAT

TTTACAATACAATAAGGGAAAAATAAAAAGTTATTTAAGTTATTCATACTTTCTTCTTCTTTTC

TTTTTTGCTATAGAAAGTATTTATTTTTTCTGGAACATTTAGAAAAAA

SEQ ID NO: 27289 (5Ή arm)

Suitable sequence for the 3' homology arm can be selected from (e.g., includes a portion of) or include the following sequence:

TTGGATCCCTATGAACAGTGGAGTGATCAAGAAATATGGAAAGTTGCAGATGAGGTAAGGCTGC TAACTGAAATGATTTTGAAAGGGGTAACTCATACCAACACAAATGGCTGATATAGCTGACATCA TTCTACACACTTTGTGTGCATGTATGTGTGTGCACAACTTTAAAATGGAGTACCCTAACATACC TGGAGCAACAGGTACTTTTGACTGGACCTACCCCTAACTGAAATGATTTTGAAAGAGGTAACTC ATACCAACACAAATGGTTGATATGGCTAAGATCATTCTACACACTTTGTGTGCATGTATTTCTG TGCACAACTTCAAAATGGAGTACCCTAAAATACCTGGCGCGACAAGTACTTTTGACTGAGCCTA CTTCTCTCCTCACTGGTATGGCTCCAACCATCAGGCCCTATCTTGGTCCATTTAGGCTGCTAAA ATAAAATACCAAAGACTGAGCTGCTTATAAGCAATCTTTGGAGGCTGAGAAGTCAAAGATCAAG GTGCCAGCAGGTTTGCTGTCTCGTGAGAGCATACTTCCTGGTTCATTGATGGTGCTTTCTTGCT GTGTCCTCACATAATGGAAAGGGCAAGACCTCTCTGGTGTCTCTTTTACAATGGCACTAATCCC ATCATGAGGGCTTTGTTCTCATGACCTAATCACCTCCCACATGTCCTACATTCTAATACTATCA CCTTGGGGGTTAGGATTTTAACATATGAATTTGAGGAGGTGGCGGGGGGGACACAAATATTTAG ACCATAGCATTTCACTCCTGACCTCCAAAGTTCATGTCTTCTTCACATGCAAAATACATTCATT CCATCCCAATAGCCCCCAAAGTCTTAACTTGTTCCAGCATCAACTTACAAGGCTAAAGTCCAAG GTTTCATCTAAATATCAGCTAAATCAGCACAAACAGCTAAATCAGGTAGAGTGGGACTTAAGGT GTGATTCCTCTTTAGGCAGATTGCTCTCCAACTATGAAATTGTGAAATCAAACCTATTATGTAC TTTCAAAATAAAATGGTGAAACAGGCACAGGCTAGACAGTCCCATTTCAAAAAAGAGAAATAGA AAAGAAAAAAGGAGTGACAGGTCTCTATAAGTCTAAAACT T TAAGGCT TGAGAATAAT T TGCT T

TGCT T TGCCTCCAGGCTCACTGGGGTGGTGTCT TACCTCTGGACACAC

SEQ ID NO: 27290 (3Ή arm)

In an embodiment, the replacement sequence comprises or consists of a Cytosine (C) residue.

In an embodiment, to correct a mutation, e.g., N1303K target site in the CFTR gene, the homology arms, e.g., the 5' and 3' homology arms, may each comprise about 1000 base pairs (bp) of sequence flanking the most distal gRNAs (e.g., 1200bp of sequence on either side of the mutation). The 5' homology arm is shown as bold sequence, the inserted base to correct the G542X mutation is shown as lower case sequence, and the 3' homology arm is shown as no emphasis capitalized sequence.

GTTTCTGAGACATTTGACAACAACTTTTTCTTTAAGTCATCAGTTATGCCCCGGGGTATGAAAT TTCTAACATGATCCTCAGTAAACTTGGCTGCCTTGCTGAGGATACTCTCCATCTGCCTGAGAGA CACAGACACCATTAATTGGGAATTGACTTGACTTGTGTGGTTCCTTGTGGACCAGATGGCCACT AAATATTCTCATTTCAAGGCAATTGGTAAAAACTACACTTCAAGAAATTTCATTCTTAATTCCC CTTAGTGGATGTTATTAACCAAAGGCAAAAGAAAAAAAGGGTAAAAAAAATATTCTAAATGTTA ATATCAAAAATATTATTTTCAATTCACCCCAGGCACAGAGAACTAAGTATTATTATTGCTATTG CACCGGCATTCCCCAATGAGACAGTGATTTTCTTTTAAGACATTTTTAAATAATATAGGCAGAA TTAAGTAGACGGTGATCTGGTAAGTAGATGTTTCAGGGTAACAGCTGTGCAATGCTCCATGCAG GGAATTAGATTGTCATTTTATTCCTTACCAGGAACATACATTCAGTTAAACAATTATTTGACTT CTGCTCTTCCACTGATTTCTAAGTTGAGGCTCTCTCTTGTGCCTGTCTGATCAGATAAGTAGAG TTGTGCCTTGGTTTATAGATGAGATAAATGTGTATTTGAATAAGCATAAGTTAAAGAAATTTTA AAATCCCTTAGGAAGCTAGGCTTATCAGAGAAATCCAAGGAAATACATTAACAAACTAGGAATT TGTTCTAACAGGTTAATTATAACTCATAAACTTATTGGGTTTTTTTACCTTTTAATTTTATATT ACATTTGCTTATAATAAGGAATATTGCTAGGAATAAAATTTTTTAATATTCTACAATTAACAAT TATCTCAATTTCTTTATTCTAAAGACATTGGGATTAGAAAAATGTTCACAAGGGACTCCAAATA TTGCTGTAGTATTTGTTTCTTAAAAGAATGATACAAAGCAGACATGATAAAATATTAAAATTTG AGAGAACTTGATGGTAAGTACATGGGTGTTTCTTATTTTAAAATAATTTTTCTACTTGAAATAT TTTACAATACAATAAGGGAAAAATAAAAAGTTATTTAAGTTATTCATACTTTCTTCTTCTTTTC TTTTTTGCTATAGAAAGTATTTATTTTTTCTGGAACATTTAGAAAAAAc T TGGATCCCTAT G AA CAGTGGAGTGATCAAGAAATATGGAAAGT TGCAGATGAGGTAAGGCTGCTAACTGAAATGAT T T TGAAAGGGGTAACTCATACCAACACAAATGGCTGATATAGCTGACATCATTCTACACACTTTGT

GTGCATGTATGTGTGTGCACAACTTTAAAATGGAGTACCCTAACATACCTGGAGCAACAGGTAC

TTTTGACTGGACCTACCCCTAACTGAAATGATTTTGAAAGAGGTAACTCATACCAACACAAATG

GTTGATATGGCTAAGATCATTCTACACACTTTGTGTGCATGTATTTCTGTGCACAACTTCAAAA

TGGAGTACCCTAAAATACCTGGCGCGACAAGTACTTTTGACTGAGCCTACTTCTCTCCTCACTG

GTATGGCTCCAACCATCAGGCCCTATCTTGGTCCATTTAGGCTGCTAAAATAAAATACCAAAGA

CTGAGCTGCTTATAAGCAATCTTTGGAGGCTGAGAAGTCAAAGATCAAGGTGCCAGCAGGTTTG

CTGTCTCGTGAGAGCATACTTCCTGGTTCATTGATGGTGCTTTCTTGCTGTGTCCTCACATAAT

GGAAAGGGCAAGACCTCTCTGGTGTCTCTTTTACAATGGCACTAATCCCATCATGAGGGCTTTG

TTCTCATGACCTAATCACCTCCCACATGTCCTACATTCTAATACTATCACCTTGGGGGTTAGGA

TTTTAACATATGAATTTGAGGAGGTGGCGGGGGGGACACAAATATTTAGACCATAGCATTTCAC

TCCTGACCTCCAAAGTTCATGTCTTCTTCACATGCAAAATACATTCATTCCATCCCAATAGCCC

CCAAAGTCTTAACTTGTTCCAGCATCAACTTACAAGGCTAAAGTCCAAGGTTTCATCTAAATAT

CAGCTAAATCAGCACAAACAGCTAAATCAGGTAGAGTGGGACTTAAGGTGTGATTCCTCTTTAG

GCAGATTGCTCTCCAACTATGAAATTGTGAAATCAAACCTATTATGTACTTTCAAAATAAAATG

GTGAAACAGGCACAGGCTAGACAGTCCCATTTCAAAAAAGAGAAATAGAAAAGAAAAAAGGAGT

GACAGGTCTCTATAAGTCTAAAACTTTAAGGCTTGAGAATAATTTGCTTTGCTTTGCCTCCAGG

CTCACTGGGGTGGTGTCTTACCTCTGGACACAC

(Template Construct 19; SEQ ID NO: 27291)

As described below in Table 49, shorter homology arms, e.g., 5' and/or 3' homology arms may be used.

It is contemplated herein that one or both homology arms may be shortened to avoid including certain sequence repeat elements, e.g., Alu repeats, LINE elements. For example, a 5' homology arm may be shortened to avoid a sequence repeat element. In other embodiments, a 3' homology arm may be shortened to avoid a sequence repeat element. In some embodiments, both the 5' and the 3' homology arms may be shortened to avoid including certain sequence repeat elements.

In an embodiment, to correct N1303K mutation in the CFTR gene, the 5' homology arm may be shortened less than 1000 nucleotides, e.g., e.g., 500 nucleotides, to avoid inclusion of a LINE repeat element in the 5' homology arm. The 5' homology arm is shown as bold sequence, the inserted base to correct the N1303K mutation is shown as lower case sequence, and the 3' homology arm is shown as no emphasis capitalized sequence.

TTTAAAATCCCTTAGGAAGCTAGGCTTATCAGAGAAATCCAAGGAAATACATTAACAAACTAGG

AATTTGTTCTAACAGGTTAATTATAACTCATAAACTTATTGGGTTTTTTTACCTTTTAATTTTA

TATTACATTTGCTTATAATAAGGAATATTGCTAGGAATAAAATTTTTTAATATTCTACAATTAA

CAATTATCTCAATTTCTTTATTCTAAAGACATTGGGATTAGAAAAATGTTCACAAGGGACTCCA

AATATTGCTGTAGTATTTGTTTCTTAAAAGAATGATACAAAGCAGACATGATAAAATATTAAAA

TTTGAGAGAACTTGATGGTAAGTACATGGGTGTTTCTTATTTTAAAATAATTTTTCTACTTGAA

ATATTTTACAATACAATAAGGGAAAAATAAAAAGTTATTTAAGTTATTCATACTTTCTTCTTCT

TTTCTTTTTTGCTATAGAAAGTATTTATTTTTTCTGGAACATTTAGAAAAAAc T TGGATCCCTA

TGAACAGTGGAGTGATCAAGAAATATGGAAAGT TGCAGATGAGGTAAGGCTGCTAACTGAAATG

AT T T TGAAAGGGGTAACTCATACCAACACAAATGGCTGATATAGCTGACATCAT TCTACACACT

T TGTGTGCATGTATGTGTGTGCACAACT T TAAAATGGAGTACCCTAACATACCTGGAGCAACAG

GTACT T T TGACTGGACCTACCCCTAACTGAAATGAT T T TGAAAGAGGTAACTCATACCAACACA

AATGGT TGATATGGCTAAGATCAT TCTACACACT T TGTGTGCATGTAT T TCTGTGCACAACT TC

AAAATGGAGTACCCTAAAATACCTGGCGCGACAAGTACT T T TGACTGAGCCTACT TCTCTCCTC

ACTGGTATGGCTCCAACCATCAGGCCCTATCT TGGTCCAT T TAGGCTGCTAAAATAAAATACCA

AAGACTGAGCTGCT TATAAGCAATCT T TGGAGGCTGAGAAG

(Template Construct 20; SEQ ID NO: 27292)

It is contemplated herein that template nucleic acids for correcting a mutation may designed for use as a single- stranded oligonucleotide (ssODN). When using a ssODN, 5' and 3' homology arms may range up to about 200 base pairs (bp) in length, e.g., at least 25, 50, 75, 100, 125, 150, 175, or 200 bp in length. Longer homology arms are also contemplated for ssODNs as improvements in oligonucleotide synthesis continue to be made.

In an embodiment, an ssODN may be used to correct a mutation, e.g., N1303K target site in the CFTR gene. For example, the ssODN may include 5' and 3' homology arms as shown below. The 5' homology arm is shown as bold sequence, the inserted bases to correct the N1303K mutation is shown as lower case sequence, and the 3' homology arm is shown as no emphasis capitalized sequence. AGTTATTCATACTTTCTTCTTCTTTTCTTTTTTGCTATAGAAAGTATTTATTTTTTCTGGAACA

TTTAGAAAAAAcT TGGATCCCTATGAACAGTGGAGTGATCAAGAAATATGGAAAGT TGCAGATG

AGGTAAGGCTGCTAACTGAAATG

(Template Construct 21; SEQ ID NO: 27293)

In an embodiment, to correct a mutation, e.g., N1303K target site in the CFTR gene, and concomitantly introduce a silent sense mutation to disrupt subsequent Cas9 binding and cleavage, the homology arms, e.g., the 5' and 3' homology arms, may each comprise about 1000 base pairs (bp) of sequence flanking the most distal gRNAs (e.g., 1200bp of sequence on either side of the mutation). The 5' homology arm is shown as bold sequence, the inserted base to correct the N1303K mutation is shown as lower case sequence, the silent sense mutation is shown as lower case underlined and italicized sequence, and the 3' homology arm is shown as no emphasis capitalized sequence.

GTTTCTGAGACATTTGACAACAACTTTTTCTTTAAGTCATCAGTTATGCCCCGGGGTATGAAAT TTCTAACATGATCCTCAGTAAACTTGGCTGCCTTGCTGAGGATACTCTCCATCTGCCTGAGAGA CACAGACACCATTAATTGGGAATTGACTTGACTTGTGTGGTTCCTTGTGGACCAGATGGCCACT AAATATTCTCATTTCAAGGCAATTGGTAAAAACTACACTTCAAGAAATTTCATTCTTAATTCCC CTTAGTGGATGTTATTAACCAAAGGCAAAAGAAAAAAAGGGTAAAAAAAATATTCTAAATGTTA ATATCAAAAATATTATTTTCAATTCACCCCAGGCACAGAGAACTAAGTATTATTATTGCTATTG CACCGGCATTCCCCAATGAGACAGTGATTTTCTTTTAAGACATTTTTAAATAATATAGGCAGAA TTAAGTAGACGGTGATCTGGTAAGTAGATGTTTCAGGGTAACAGCTGTGCAATGCTCCATGCAG GGAATTAGATTGTCATTTTATTCCTTACCAGGAACATACATTCAGTTAAACAATTATTTGACTT CTGCTCTTCCACTGATTTCTAAGTTGAGGCTCTCTCTTGTGCCTGTCTGATCAGATAAGTAGAG TTGTGCCTTGGTTTATAGATGAGATAAATGTGTATTTGAATAAGCATAAGTTAAAGAAATTTTA AAATCCCTTAGGAAGCTAGGCTTATCAGAGAAATCCAAGGAAATACATTAACAAACTAGGAATT TGTTCTAACAGGTTAATTATAACTCATAAACTTATTGGGTTTTTTTACCTTTTAATTTTATATT ACATTTGCTTATAATAAGGAATATTGCTAGGAATAAAATTTTTTAATATTCTACAATTAACAAT TATCTCAATTTCTTTATTCTAAAGACATTGGGATTAGAAAAATGTTCACAAGGGACTCCAAATA TTGCTGTAGTATTTGTTTCTTAAAAGAATGATACAAAGCAGACATGATAAAATATTAAAATTTG AGAGAACTTGATGGTAAGTACATGGGTGTTTCTTATTTTAAAATAATTTTTCTACTTGAAATAT TTTACAATACAATAAGGGAAAAATAAAAAGTTATTTAAGTTATTCATACTTTCTTCTTCTTTTC TTTTTTGCTATAGAAAGTATTTATTTTTTCTGGAACATTTAGAAAAAAc cT cGATCCCTATGAA CAGTGGAGTGATCAAGAAATATGGAAAGTTGCAGATGAGGTAAGGCTGCTAACTGAAATGATTT

TGAAAGGGGTAACTCATACCAACACAAATGGCTGATATAGCTGACATCATTCTACACACTTTGT

GTGCATGTATGTGTGTGCACAACTTTAAAATGGAGTACCCTAACATACCTGGAGCAACAGGTAC

TTTTGACTGGACCTACCCCTAACTGAAATGATTTTGAAAGAGGTAACTCATACCAACACAAATG

GTTGATATGGCTAAGATCATTCTACACACTTTGTGTGCATGTATTTCTGTGCACAACTTCAAAA

TGGAGTACCCTAAAATACCTGGCGCGACAAGTACTTTTGACTGAGCCTACTTCTCTCCTCACTG

GTATGGCTCCAACCATCAGGCCCTATCTTGGTCCATTTAGGCTGCTAAAATAAAATACCAAAGA

CTGAGCTGCTTATAAGCAATCTTTGGAGGCTGAGAAGTCAAAGATCAAGGTGCCAGCAGGTTTG

CTGTCTCGTGAGAGCATACTTCCTGGTTCATTGATGGTGCTTTCTTGCTGTGTCCTCACATAAT

GGAAAGGGCAAGACCTCTCTGGTGTCTCTTTTACAATGGCACTAATCCCATCATGAGGGCTTTG

TTCTCATGACCTAATCACCTCCCACATGTCCTACATTCTAATACTATCACCTTGGGGGTTAGGA

TTTTAACATATGAATTTGAGGAGGTGGCGGGGGGGACACAAATATTTAGACCATAGCATTTCAC

TCCTGACCTCCAAAGTTCATGTCTTCTTCACATGCAAAATACATTCATTCCATCCCAATAGCCC

CCAAAGTCTTAACTTGTTCCAGCATCAACTTACAAGGCTAAAGTCCAAGGTTTCATCTAAATAT

CAGCTAAATCAGCACAAACAGCTAAATCAGGTAGAGTGGGACTTAAGGTGTGATTCCTCTTTAG

GCAGATTGCTCTCCAACTATGAAATTGTGAAATCAAACCTATTATGTACTTTCAAAATAAAATG

GTGAAACAGGCACAGGCTAGACAGTCCCATTTCAAAAAAGAGAAATAGAAAAGAAAAAAGGAGT

GACAGGTCTCTATAAGTCTAAAACTTTAAGGCTTGAGAATAATTTGCTTTGCTTTGCCTCCAGG

CTCACTGGGGTGGTGTCTTACCTCTGGACACAC

(Template Construct 22; SEQ ID NO: 27294)

In an embodiment, to correct a mutation, e.g., N1303K target site in the CFTR gene, and concomitantly introduce a silent mutation to disrupt subsequent Cas9 binding and cleavage, the 5' homology arm may be shortened less than 750 nucleotides, e.g., 500 nucleotides, to avoid inclusion of a LINE repeat element in the 5' homology arm. The 5' homology arm is shown as bold sequence, the inserted base to correct the N1303K mutation is shown as lower case sequence, the silent sense mutation is shown as lower case underlined and italicized sequence, and the 3' homology arm is shown as no emphasis capitalized sequence.

TTTAAAATCCCTTAGGAAGCTAGGCTTATCAGAGAAATCCAAGGAAATACATTAACAAACTAGG AATTTGTTCTAACAGGTTAATTATAACTCATAAACTTATTGGGTTTTTTTACCTTTTAATTTTA TATTACATTTGCTTATAATAAGGAATATTGCTAGGAATAAAATTTTTTAATATTCTACAATTAA CAATTATCTCAATTTCTTTATTCTAAAGACATTGGGATTAGAAAAATGTTCACAAGGGACTCCA AATATTGCTGTAGTATTTGTTTCTTAAAAGAATGATACAAAGCAGACATGATAAAATATTAAAA TTTGAGAGAACTTGATGGTAAGTACATGGGTGTTTCTTATTTTAAAATAATTTTTCTACTTGAA ATATTTTACAATACAATAAGGGAAAAATAAAAAGTTATTTAAGTTATTCATACTTTCTTCTTCT TTTCTTTTTTGCTATAGAAAGTATTTATTTTTTCTGGAACATTTAGAAAAAAc cT cGATCCCTA

TGAACAGTGGAGTGATCAAGAAATATGGAAAGT TGCAGATGAGGTAAGGCTGCTAACTGAAATG

AT T T TGAAAGGGGTAACTCATACCAACACAAATGGCTGATATAGCTGACATCAT TCTACACACT

T TGTGTGCATGTATGTGTGTGCACAACT T TAAAATGGAGTACCCTAACATACCTGGAGCAACAG

GTACT T T TGACTGGACCTACCCCTAACTGAAATGAT T T TGAAAGAGGTAACTCATACCAACACA

AATGGT TGATATGGCTAAGATCAT TCTACACACT T TGTGTGCATGTAT T TCTGTGCACAACT TC

AAAATGGAGTACCCTAAAATACCTGGCGCGACAAGTACT T T TGACTGAGCCTACT TCTCTCCTC

ACTGGTATGGCTCCAACCATCAGGCCCTATCT TGGTCCAT T TAGGCTGCTAAAATAAAATACCA

AAGACTGAGCTGCT TATAAGCAATCT T TGGAGGCTGAGAAG

(Template Construct 23; SEQ ID NO: 27295)

In an embodiment, an ssODN may be to correct a mutation, e.g., N1303K target site in the CFTR gene, and concomitantly introduce a silent mutation to disrupt subsequent Cas9 binding and cleavage. For example, the ssODN may include 5' and 3' homology arms as shown below. The 5' homology arm is shown as bold sequence, the inserted base to correct the N1303K mutation is shown as lower case sequence, the silent sense mutation is shown as lower case underlined and italicized sequence, and the 3' homology arm is shown as no emphasis capitalized sequence.

AGTTATTCATACTTTCTTCTTCTTTTCTTTTTTGCTATAGAAAGTATTTATTTTTTCTGGAACA

TTTAGAAAAAAccTcGATCCCTATGAACAGTGGAGTGATCAAGAAATATGGAAAGTTGCAGATG

AGGTAAGGCTGCTAACTGAAATG

(Template Construct 24; SEQ ID NO: 27296)

The underlined C has been changed from a G to C so that wild-type CFTR is still transcribed, but the PAM sequence TGG has been modified to reduce or eliminate Cas9 cleavage at that locus.

Exemplary template nucleic acids (also referred to herein as donor constructs) to correction a mutation, e.g., Rl 17H target site in the CFTR gene, are provided.

Suitable sequence for the 5' homology arm can be selected from (e.g., includes a portion of) or include the following sequence: AACCCCTCAAATTAAGGGATGAGGCAGAATAATGCTTGGCAATACCAGGGGTAGGCTGCAGTCT

TTCTTGGAAATATATATTTTAAATGGAACCAATTATCATAGCATCATTTCCTCTCAGGGTTACC

CTCTGATCCCTATTTTACTAAATCGTTATAAAACAAAATGAGGAATTATGTGTCCTTCCCTTTT

GAAGCCAATGTAACAAGATGGGTAAGAATTAGACCTCCTGAGTTCAAAATCCCTGGATTCAGAT

CTATTCCTGTATATTCAGGAGAAGTGGTAATAAATTCGATGGACAATTTGGTTTAGTAGTCGAT

TGAGGACCCTGATGAGGTATATTTGGGAAAACATAACTTCCGCTCTCTCTCATTGACTCACGGG

CCTTTGAGGAGTCCAGGAGTCATTGGAATCTGGCCTGAGGTTGAGGCTGCTGGCAAAACTCCTT

CCCCAAAGTCCATTCCTATTGCTGACTGAGAAGGGACTAGCATTGGAAGTGGCTGATTTTAAAT

ACCGCTAGTGCTGGTGTGCTCCTCCCTCCCATTCCCAGCTCTGCTTTGTGTAGTTGCCTTGAGA

AGCTAAGTTCATTCTGAAAATAATGCCATTGCACAAAACACTTTTGAAAGTTCTAGTTTGAAAT

TACATCAGGTCACTTGGTCTGTGTGGCCTCAGTTTCTTCATCTGCCATGTGAAAATAATAATGC

CTACTCTGT AG C AAAG AAAG TCTCTATAGT AAAC AAAAAAAAAG CCTACTCTGATACT G AAAG T

TGTTATGAAAAATAAAAAAGGGAAATGCTTTAGAAACTGTTAAGTGCTATGTAGATGTTACTAA

TTAACAAACCATTTCAGAAACTATACTTTTTATTTTATGGCCACTATTCACTGTTTAACTTAAA

ATACCTCATATGTAAACTTGTCTCCCACTGTTGCTATAACAAATCCCAAGTCTTATTTCAAAGT

ACCAAGATATTGAAAATAGTGCTAAGAGTTTCACATATGGTATGACCCTCTATATAAACTCATT

TTAAGTCTCCTCTAAAGATGAAAAGTCTTGTGTTGAAATTCTCAGGGTATTTTATGAGAAATAA

ATGAAATTTAATTTCTCTGTTTTTCCCCTTTTGTAGGAAGTCACCAAAGCAGTACAGCCTCTCT

TACTGGGAAGAATCATAGCTTCCTATGACCCGGATAACAAGGAGGAAC

SEQ ID NO: 27297 (5Ή arm)

Suitable sequence for the 3' homology arm can be selected from (e.g., includes a portion of) or include the following sequence:

CTCTATCGCGATTTATCTAGGCATAGGCTTATGCCTTCTCTTTATTGTGAGGACACTGCTCCTA CACCCAGCCATTTTTGGCCTTCATCACATTGGAATGCAGATGAGAATAGCTATGTTTAGTTTGA TTTATAAGAAGGTAATACTTCCTTGCACAGGCCCCATGGCACATATATTCTGTATCGTACATGT TTTAATGTCATAAATTAGGTAGTGAGCTGGTACAAGTAAGGGATAAATGCTGAAATTAATTTAA TATGCCTATTAAATAAATGGCAGGAATAATTAATGCTCTTAATTATCCTTGATAATTTAATTGA CTTAAACTGATAATTATTGAGTATCTTCTGTAAACTGCCTCTGTTGTAGTTTTTTTTTTCTCCT AATCATGTTATCATTTTTTTGGAATCCATGGTTTCCTGTTAAGATGACTCACACAGCCTACATA AAAGTAATTGACAAAATATCATCTTATAGTAAAATGCCACATATCTTTATGTTCAGCAAGAAGA GTATAATATATGATTGTTAATGATAACCCAAACAACAAAAGATTTCACCTTAACTGGTTGTCAT AAGTAGTAGTATCCACCGCCTTATTTTGAGTTGGATTTTTATCATCCTATGAGCCCTACAAATT TAAAGTTTTTGGAACAGCACGTGCATTGAACCCATAAGAACCTACTCTGCTTTTCTGCATGTAT

TGTCCAGACAAGAGACCAAATTGCCGAGGCATCATTTAGGTGAATTCTAATTAACATTTAGCTA

CCTTACAACCACAATTCAAGGTTGTTTCAAAGGCATGTGCTTGCATCATCCTGATTCACTACCA

TGTGTTACTAACTTGGATCTGCAAAGTCATTATAAAAAGCTGTTTTGATGGACTTATTTGGATA

TTGCTTTACCCTTCTTCTCTCTTTTCTTTTATCAATGTAAAAACATTATATGTTAAATACTTGG

CTTTTAAGAGCATAGATCTGAAATCTGCCTCTAGCAAATAACCCATAACACTTCTAAGATATAC

CTGCAAGGTCAATTGTGTTGTAAAACCTTGATAACCATACTTTATTGTTCAAAAAAGCCTTTTA

TGAAGGCAGAAGTTAAAAAAAAAAAACAAAAAAAACAGAGTCCACAGTTATCACCTCAGCTACA

ATCTCATCAGTTCACAAGTACCAGCAAAACATGTGATAAGTCAACAAA

SEQ ID NO: 27298 (3Ή arm)

In an embodiment, the replacement sequence comprises or consists of a Guanine (G) residue.

In an embodiment, to correct a mutation, e.g., Rl 17H target site in the CFTR gene, the homology arms, e.g., the 5' and 3' homology arms, may each comprise about 1000 base pairs (bp) of sequence flanking the most distal gRNAs (e.g., 1200bp of sequence on either side of the mutation). The 5' homology arm is shown as bold sequence, the inserted base to correct the Rl 17H mutation is shown as lower case sequence, and the 3' homology arm is shown as no emphasis capitalized sequence.

AACCCCTCAAATTAAGGGATGAGGCAGAATAATGCTTGGCAATACCAGGGGTAGGCTGCAGTCT TTCTTGGAAATATATATTTTAAATGGAACCAATTATCATAGCATCATTTCCTCTCAGGGTTACC CTCTGATCCCTATTTTACTAAATCGTTATAAAACAAAATGAGGAATTATGTGTCCTTCCCTTTT GAAGCCAATGTAACAAGATGGGTAAGAATTAGACCTCCTGAGTTCAAAATCCCTGGATTCAGAT CTATTCCTGTATATTCAGGAGAAGTGGTAATAAATTCGATGGACAATTTGGTTTAGTAGTCGAT TGAGGACCCTGATGAGGTATATTTGGGAAAACATAACTTCCGCTCTCTCTCATTGACTCACGGG CCTTTGAGGAGTCCAGGAGTCATTGGAATCTGGCCTGAGGTTGAGGCTGCTGGCAAAACTCCTT CCCCAAAGTCCATTCCTATTGCTGACTGAGAAGGGACTAGCATTGGAAGTGGCTGATTTTAAAT ACCGCTAGTGCTGGTGTGCTCCTCCCTCCCATTCCCAGCTCTGCTTTGTGTAGTTGCCTTGAGA AGCTAAGTTCATTCTGAAAATAATGCCATTGCACAAAACACTTTTGAAAGTTCTAGTTTGAAAT TACATCAGGTCACTTGGTCTGTGTGGCCTCAGTTTCTTCATCTGCCATGTGAAAATAATAATGC CTACTCTGTAGCAAAGAAAGTCTCTATAGTAAACAAAAAAAAAGCCTACTCTGATACTGAAAGT TGTTATGAAAAATAAAAAAGGGAAATGCTTTAGAAACTGTTAAGTGCTATGTAGATGTTACTAA TTAACAAACCATTTCAGAAACTATACTTTTTATTTTATGGCCACTATTCACTGTTTAACTTAAA

ATACCTCATATGTAAACTTGTCTCCCACTGTTGCTATAACAAATCCCAAGTCTTATTTCAAAGT

ACCAAGATATTGAAAATAGTGCTAAGAGTTTCACATATGGTATGACCCTCTATATAAACTCATT

TTAAGTCTCCTCTAAAGATGAAAAGTCTTGTGTTGAAATTCTCAGGGTATTTTATGAGAAATAA

ATGAAATTTAATTTCTCTGTTTTTCCCCTTTTGTAGGAAGTCACCAAAGCAGTACAGCCTCTCT

TACTGGGAAGAATCATAGCTTCCTATGACCCGGATAACAAGGAGGAACgC T C T AT CGCGAT T T A

TCTAGGCATAGGCTTATGCCTTCTCTTTATTGTGAGGACACTGCTCCTACACCCAGCCATTTTT

GGCCTTCATCACATTGGAATGCAGATGAGAATAGCTATGTTTAGTTTGATTTATAAGAAGGTAA

TACTTCCTTGCACAGGCCCCATGGCACATATATTCTGTATCGTACATGTTTTAATGTCATAAAT

TAGGTAGTGAGCTGGTACAAGTAAGGGATAAATGCTGAAATTAATTTAATATGCCTATTAAATA

AATGGCAGGAATAATTAATGCTCTTAATTATCCTTGATAATTTAATTGACTTAAACTGATAATT

ATTGAGTATCTTCTGTAAACTGCCTCTGTTGTAGTTTTTTTTTTCTCCTAATCATGTTATCATT

TTTTTGGAATCCATGGTTTCCTGTTAAGATGACTCACACAGCCTACATAAAAGTAATTGACAAA

ATATCATCTTATAGTAAAATGCCACATATCTTTATGTTCAGCAAGAAGAGTATAATATATGATT

GTTAATGATAACCCAAACAACAAAAGATTTCACCTTAACTGGTTGTCATAAGTAGTAGTATCCA

CCGCCTTATTTTGAGTTGGATTTTTATCATCCTATGAGCCCTACAAATTTAAAGTTTTTGGAAC

AGCACGTGCATTGAACCCATAAGAACCTACTCTGCTTTTCTGCATGTATTGTCCAGACAAGAGA

CCAAATTGCCGAGGCATCATTTAGGTGAATTCTAATTAACATTTAGCTACCTTACAACCACAAT

TCAAGGTTGTTTCAAAGGCATGTGCTTGCATCATCCTGATTCACTACCATGTGTTACTAACTTG

GATCTGCAAAGTCATTATAAAAAGCTGTTTTGATGGACTTATTTGGATATTGCTTTACCCTTCT

TCTCTCTTTTCTTTTATCAATGTAAAAACATTATATGTTAAATACTTGGCTTTTAAGAGCATAG

ATCTGAAATCTGCCTCTAGCAAATAACCCATAACACTTCTAAGATATACCTGCAAGGTCAATTG

TGTTGTAAAACCTTGATAACCATACTTTATTGTTCAAAAAAGCCTTTTATGAAGGCAGAAGTTA

AAAAAAAAAAACAAAAAAAACAGAGTCCACAGTTATCACCTCAGCTACAATCTCATCAGTTCAC

AAGTACCAGCAAAACATGTGATAAGTCAACAAA

(Template Construct 25; SEQ ID NO: 27299)

As described below in Table 49, shorter homology arms, e.g., 5' and/or 3' homology arms may be used.

It is contemplated herein that one or both homology arms may be shortened to avoid including certain sequence repeat elements, e.g., Alu repeats, LINE elements. For example, a 5' homology arm may be shortened to avoid a sequence repeat element. In other embodiments, a 3' homology arm may be shortened to avoid a sequence repeat element. In some embodiments, both the 5' and the 3' homology arms may be shortened to avoid including certain sequence repeat elements.

In an embodiment, to correct Rl 17H mutation in the CFTR gene, the 5' homology arm may be shortened less than 1000 nucleotides, e.g., e.g., 500 nucleotides, to avoid inclusion of a LINE repeat element in the 5' homology arm. The 5' homology arm is shown as bold sequence, the inserted base to correct the Rl 17H mutation is shown as lower case sequence, and the 3' homology arm is shown as no emphasis capitalized sequence.

ATGCCTACTCTGTAGCAAAGAAAGTCTCTATAGTAAACAAAAAAAAAGCCTACTCTGATACTGA

AAGTTGTTATGAAAAATAAAAAAGGGAAATGCTTTAGAAACTGTTAAGTGCTATGTAGATGTTA

CTAATTAACAAACCATTTCAGAAACTATACTTTTTATTTTATGGCCACTATTCACTGTTTAACT

TAAAATACCTCATATGTAAACTTGTCTCCCACTGTTGCTATAACAAATCCCAAGTCTTATTTCA

AAGTACCAAGATATTGAAAATAGTGCTAAGAGTTTCACATATGGTATGACCCTCTATATAAACT

CATTTTAAGTCTCCTCTAAAGATGAAAAGTCTTGTGTTGAAATTCTCAGGGTATTTTATGAGAA

ATAAATGAAATTTAATTTCTCTGTTTTTCCCCTTTTGTAGGAAGTCACCAAAGCAGTACAGCCT

CTCTTACTGGGAAGAATCATAGCTTCCTATGACCCGGATAACAAGGAGGAACgC T C T AT CGCGA

TTTATCTAGGCATAGGCTTATGCCTTCTCTTTATTGTGAGGACACTGCTCCTACACCCAGCCAT

TTTTGGCCTTCATCACATTGGAATGCAGATGAGAATAGCTATGTTTAGTTTGATTTATAAGAAG

GTAATACTTCCTTGCACAGGCCCCATGGCACATATATTCTGTATCGTACATGTTTTAATGTCAT

AAATTAGGTAGTGAGCTGGTACAAGTAAGGGATAAATGCTGAAATTAATTTAATATGCCTATTA

AATAAATGGCAGGAATAATTAATGCTCTTAATTATCCTTGATAATTTAATTGACTTAAACTGAT

AATTATTGAGTATCTTCTGTAAACTGCCTCTGTTGTAGTTTTTTTTTTCTCCTAATCATGTTAT

CATTTTTTTGGAATCCATGGTTTCCTGTTAAGATGACTCACACAGCCTACATAAAAGTAATTGA

CAAAATATCATCTTATAGTAAAATGCCACATATCTTTATGT

(Template Construct 26; SEQ ID NO: 27300)

It is contemplated herein that template nucleic acids for correcting a mutation may designed for use as a single- stranded oligonucleotide (ssODN). When using a ssODN, 5' and 3' homology arms may range up to about 200 base pairs (bp) in length, e.g., at least 25, 50, 75, 100, 125, 150, 175, or 200 bp in length. Longer homology arms are also contemplated for ssODNs as improvements in oligonucleotide synthesis continue to be made.

In an embodiment, an ssODN may be used to correct a mutation, e.g., Rl 17H target site in the CFTR gene. For example, the ssODN may include 5' and 3' homology arms as shown below. The 5' homology arm is shown as bold sequence, the inserted bases to correct the Rl 17H mutation is shown as lower case sequence, and the 3' homology arm is shown as no emphasis capitalized sequence.

AAGTCACCAAAGCAGTACAGCCTCTCTTACTGGGAAGAATCATAGCTTCCTATGACCCGGATAA

CAAGGAGGAACqCTCTATCGCGAT T TATCTAGGCATAGGCT TATGCCT TCTCT T TAT TGTGAGG

ACACTGCTCCTACACCCAGCCAT

(Template Construct 27; SEQ ID NO: 27301)

In an embodiment, to correct a mutation, e.g., Rl 17H target site in the CFTR gene, and concomitantly introduce a silent sense mutation to disrupt subsequent Cas9 binding and cleavage, the homology arms, e.g., the 5' and 3' homology arms, may each comprise about 1000 base pairs (bp) of sequence flanking the most distal gRNAs (e.g., 1200bp of sequence on either side of the mutation). The 5' homology arm is shown as bold sequence, the inserted base to correct the Rl 17H mutation is shown as lower case sequence, the silent sense mutation is shown as lower case underlined and italicized sequence, and the 3' homology arm is shown as no emphasis capitalized sequence.

AACCCCTCAAATTAAGGGATGAGGCAGAATAATGCTTGGCAATACCAGGGGTAGGCTGCAGTCT TTCTTGGAAATATATATTTTAAATGGAACCAATTATCATAGCATCATTTCCTCTCAGGGTTACC CTCTGATCCCTATTTTACTAAATCGTTATAAAACAAAATGAGGAATTATGTGTCCTTCCCTTTT GAAGCCAATGTAACAAGATGGGTAAGAATTAGACCTCCTGAGTTCAAAATCCCTGGATTCAGAT CTATTCCTGTATATTCAGGAGAAGTGGTAATAAATTCGATGGACAATTTGGTTTAGTAGTCGAT TGAGGACCCTGATGAGGTATATTTGGGAAAACATAACTTCCGCTCTCTCTCATTGACTCACGGG CCTTTGAGGAGTCCAGGAGTCATTGGAATCTGGCCTGAGGTTGAGGCTGCTGGCAAAACTCCTT CCCCAAAGTCCATTCCTATTGCTGACTGAGAAGGGACTAGCATTGGAAGTGGCTGATTTTAAAT ACCGCTAGTGCTGGTGTGCTCCTCCCTCCCATTCCCAGCTCTGCTTTGTGTAGTTGCCTTGAGA AGCTAAGTTCATTCTGAAAATAATGCCATTGCACAAAACACTTTTGAAAGTTCTAGTTTGAAAT TACATCAGGTCACTTGGTCTGTGTGGCCTCAGTTTCTTCATCTGCCATGTGAAAATAATAATGC CTACTCTGTAGCAAAGAAAGTCTCTATAGTAAACAAAAAAAAAGCCTACTCTGATACTGAAAGT TGTTATGAAAAATAAAAAAGGGAAATGCTTTAGAAACTGTTAAGTGCTATGTAGATGTTACTAA TTAACAAACCATTTCAGAAACTATACTTTTTATTTTATGGCCACTATTCACTGTTTAACTTAAA ATACCTCATATGTAAACTTGTCTCCCACTGTTGCTATAACAAATCCCAAGTCTTATTTCAAAGT ACCAAGATATTGAAAATAGTGCTAAGAGTTTCACATATGGTATGACCCTCTATATAAACTCATT TTAAGTCTCCTCTAAAGATGAAAAGTCTTGTGTTGAAATTCTCAGGGTATTTTATGAGAAATAA

ATGAAATTTAATTTCTCTGTTTTTCCCCTTTTGTAGGAAGTCACCAAAGCAGTACAGCCTCTCT

TACTGGGAAGAATCATAGCTTCCTATGACCCGGATAAtAAaGAaGAACgCTCTATCGCGATTTA

TCTAGGCATAGGCTTATGCCTTCTCTTTATTGTGAGGACACTGCTCCTACACCCAGCCATTTTT

GGCCTTCATCACATTGGAATGCAGATGAGAATAGCTATGTTTAGTTTGATTTATAAGAAGGTAA

TACTTCCTTGCACAGGCCCCATGGCACATATATTCTGTATCGTACATGTTTTAATGTCATAAAT

TAGGTAGTGAGCTGGTACAAGTAAGGGATAAATGCTGAAATTAATTTAATATGCCTATTAAATA

AATGGCAGGAATAATTAATGCTCTTAATTATCCTTGATAATTTAATTGACTTAAACTGATAATT

ATTGAGTATCTTCTGTAAACTGCCTCTGTTGTAGTTTTTTTTTTCTCCTAATCATGTTATCATT

TTTTTGGAATCCATGGTTTCCTGTTAAGATGACTCACACAGCCTACATAAAAGTAATTGACAAA

ATATCATCTTATAGTAAAATGCCACATATCTTTATGTTCAGCAAGAAGAGTATAATATATGATT

GTTAATGATAACCCAAACAACAAAAGATTTCACCTTAACTGGTTGTCATAAGTAGTAGTATCCA

CCGCCTTATTTTGAGTTGGATTTTTATCATCCTATGAGCCCTACAAATTTAAAGTTTTTGGAAC

AGCACGTGCATTGAACCCATAAGAACCTACTCTGCTTTTCTGCATGTATTGTCCAGACAAGAGA

CCAAATTGCCGAGGCATCATTTAGGTGAATTCTAATTAACATTTAGCTACCTTACAACCACAAT

TCAAGGTTGTTTCAAAGGCATGTGCTTGCATCATCCTGATTCACTACCATGTGTTACTAACTTG

GATCTGCAAAGTCATTATAAAAAGCTGTTTTGATGGACTTATTTGGATATTGCTTTACCCTTCT

TCTCTCTTTTCTTTTATCAATGTAAAAACATTATATGTTAAATACTTGGCTTTTAAGAGCATAG

ATCTGAAATCTGCCTCTAGCAAATAACCCATAACACTTCTAAGATATACCTGCAAGGTCAATTG

TGTTGTAAAACCTTGATAACCATACTTTATTGTTCAAAAAAGCCTTTTATGAAGGCAGAAGTTA

AAAAAAAAAAACAAAAAAAACAGAGTCCACAGTTATCACCTCAGCTACAATCTCATCAGTTCAC

AAGTACCAGCAAAACATGTGATAAGTCAACAAA

(Template Construct 28; SEQ ID NO: 27302)

In an embodiment, to correct a mutation, e.g., Rl 17H target site in the CFTR gene, and concomitantly introduce a silent mutation to disrupt subsequent Cas9 binding and cleavage, the 5' homology arm may be shortened less than 750 nucleotides, e.g., 500 nucleotides, to avoid inclusion of a LINE repeat element in the 5' homology arm. The 5' homology arm is shown as bold sequence, the inserted base to correct the Rl 17H mutation is shown as lower case sequence, the silent sense mutation is shown as lower case underlined and italicized sequence, and the 3' homology arm is shown as no emphasis capitalized sequence. ATGCCTACTCTGTAGCAAAGAAAGTCTCTATAGTAAACAAAAAAAAAGCCTACTCTGATACTGA

AAGTTGTTATGAAAAATAAAAAAGGGAAATGCTTTAGAAACTGTTAAGTGCTATGTAGATGTTA

CTAATTAACAAACCATTTCAGAAACTATACTTTTTATTTTATGGCCACTATTCACTGTTTAACT

TAAAATACCTCATATGTAAACTTGTCTCCCACTGTTGCTATAACAAATCCCAAGTCTTATTTCA

AAGTACCAAGATATTGAAAATAGTGCTAAGAGTTTCACATATGGTATGACCCTCTATATAAACT

CATTTTAAGTCTCCTCTAAAGATGAAAAGTCTTGTGTTGAAATTCTCAGGGTATTTTATGAGAA

ATAAATGAAATTTAATTTCTCTGTTTTTCCCCTTTTGTAGGAAGTCACCAAAGCAGTACAGCCT

CTCTTACTGGGAAGAATCATAGCTTCCTATGACCCGGATAA t AAaGAaGAACgC TCTATCGCGA

TTTATCTAGGCATAGGCTTATGCCTTCTCTTTATTGTGAGGACACTGCTCCTACACCCAGCCAT

TTTTGGCCTTCATCACATTGGAATGCAGATGAGAATAGCTATGTTTAGTTTGATTTATAAGAAG

GTAATACTTCCTTGCACAGGCCCCATGGCACATATATTCTGTATCGTACATGTTTTAATGTCAT

AAATTAGGTAGTGAGCTGGTACAAGTAAGGGATAAATGCTGAAATTAATTTAATATGCCTATTA

AATAAATGGCAGGAATAATTAATGCTCTTAATTATCCTTGATAATTTAATTGACTTAAACTGAT

AATTATTGAGTATCTTCTGTAAACTGCCTCTGTTGTAGTTTTTTTTTTCTCCTAATCATGTTAT

CATTTTTTTGGAATCCATGGTTTCCTGTTAAGATGACTCACACAGCCTACATAAAAGTAATTGA

CAAAATATCATCTTATAGTAAAATGCCACATATCTTTATGT

(Template Construct 29; SEQ ID NO: 27303)

In an embodiment, an ssODN may be to correct a mutation, e.g., Rl 17H target site in the CFTR gene, and concomitantly introduce a silent mutation to disrupt subsequent Cas9 binding and cleavage. For example, the ssODN may include 5' and 3' homology arms as shown below. The 5' homology arm is shown as bold sequence, the inserted base to correct the Rl 17H mutation is shown as lower case sequence, the silent sense mutation is shown as lower case underlined and italicized sequence, and the 3' homology arm is shown as no emphasis capitalized sequence.

AAGTCACCAAAGCAGTACAGCCTCTCTTACTGGGAAGAATCATAGCTTCCTATGACCCGGATAA

tAAaGAaGAACgCTCTATCGCGATTTATCTAGGCATAGGCTTATGCCTTCTCTTTATTGTGAGG

ACACTGCTCCTACACCCAGCCAT

(Template Construct 30; SEQ ID NO: 27304)

The underlined T has been changed from an A to T at that position and each underlined A has been changed from a T to A at that position so that wild-type CFTR is still transcribed, but the PAM sequence TGG has been modified to reduce or eliminate Cas9 cleavage at that locus. Exemplary template nucleic acids (also referred to herein as donor constructs) to correction a mutation, e.g., W1282X target site in the CFTR gene, are provided.

Suitable sequence for the 5' homology arm can be selected from (e.g., includes a portion of) or include the following sequence:

T T T T T AT T AT AT AT T T T T GAAGT AT T GAT AT GT AGT GAAT TAGAAAT T T AAAAAGAAAAC AAAA

CTGTCCTTCACTACAGATTGAAAAGCATTATACTAAAAGACCATTTGCTCAGTTATAGTATATA

AAGGCCAAATGACTTAAAAACAAATTATGTAAGGAGAAGGAAACAACCATTTATTCAGTGCCAC

TAACTGTCAGCCAGTTTTTTCAGTGGTCAGTTAATGACTGCAGTAGTGTTCTACCTTGCTCAAA

GCACCCTCCTCAAGTTCTGGCATCTAAGCTGACATCAGAACACAGAGTTGGGGCTCTCTGTGGG

TCACCTCTAGCACTTGATCTCCTCATGCAGTGCATGGTGCTCTCACGTCTATGCTATGTTCTTA

TGGTCTTTAGGTAACAAGAATAATTTTCTTTCTTTTCCTTACTATACATTTTGCTTTCTGAAAT

TCCCTTCTCGCCAATCCAGGTGAATGTCAGAATGTGATTTGACAACTGTCCAAAGTACTCATTC

ACTGAGGAGTGGTAAGGCCTTCGCCCAACCTGCCTTCTCTGGGAATATACTGCTGCCTGAACAT

ATCATTGTTTATTGCCAGGCTTGAACTTCACCAAATTAATTTATTAGGGTCAACATCTAAATAT

TAGAACTATTTCAGATTAATTTTTAAGTCGTATCCACTTTGGGTACTAGATCAAATTGCAGGTC

TCTGCTTCTGGCTTGAGCCTATGTTTAGAGATGATGTGCATGAAGACACTCTTTGCTTTTCCTT

TATGCAAAATGGGCATTTTCAATCTTTTTGTCATTAGTAAAGGTCAGTGATAAAGGAAGTCTGC

ATCAGGGGTCCAATTCCTTATGGCCAGTTTCTCTATTCTGTTCCAAGGTTGTTTGTCTCCATAT

ATCAACATTGGTCAGGATTGAAAGTGTGCAACAAGGTTTGAATGAATAAGTGAAAATCTTCCAC

TGGTGACAGGATAAAATATTCCAATGGTTTTTATTGAAGTACAATACTGAATTATGTTTATGGC

ATGGTACCTATATGTCACAGAAGTGATCCCATCACTTTTACCTTATAGGTGGGCCTCTTGGGAA

GAAC TGGAT C AGGGAAGAGT AC T T T GT T AT CAGCT T T T T T GAGAC T AC T GAAC AC T GAAGGAGA

AATCCAGATCGATGGTGTGTCTTGGGATTCAATAACTTTGCAACAGTG

SEQ ID NO: 27305 (5Ή arm)

Suitable sequence for the 3' homology arm can be selected from (e.g., includes a portion of) or include the following sequence:

AGGAAAGCCTTTGGAGTGATACCACAGGTGAGCAAAAGGACTTAGCCAGAAAAAAGGCAACTAA ATTATATTTTTTACTGCTATTTGATACTTGTACTCAAGAAATTCATATTACTCTGCAAAATATA TTTGTTATGCATTGCTGTCTTTTTTCTCCAGTGCAGTTTTCTCATAGGCAGAAAAGATGTCTCT AAAAGTTTGGAATTCTCAAATTCTGGTTATTGAAATGTTCATAGCTTTGATAGTGTTTTTCAGA AGACCAAATTTACAGTGGGAGCCTTGGGCTTTTGTTTTTTAACAGCTCTTTTTTGTTCCTGCTT CAGTGGCCTGACCTCCAAGTTAGCAATCGCCAGGTTGAGAAATGCTTTGCGAGACATAACAGAT GCTCCTGAAATAACAAACACTTGGAATCATGAGGTAGTGGAATTGAAAATAGAAAGTGTAGTGA

TTGTTTTTTGTTATTTGGATGGGATGAACAATGTCAGATTAGTCTGTAACTATTTTTTTTTAAT

GTCACTCTGATTTGGTCACAAAGGATCTCTAGTCTCATTGCCTTAGTATCATTCTACGAATTAG

AATGTGTTACTGTGTAAGAGCACTTCTTGTATATGAGAGAAATAGCAACAGTTCCAGTTTAAAG

TGATATAAATGGAAACCAAGAAATGTCTTTACTGGGACCAAATCTGGACAGCATTTACTGTATT

TTTGCTGGTATTTTCTCTAGTCTTTCCGGGTATATTCACATTTAATGATCACTTTTCTCCCTTT

GTGCTAATGGACACTGAATCCATTCCACTACCATAGTTCTTGCTAATACTACTCTACTTTTTAC

ACAAAATTAAAATGCCAGGAGCACCTCCAGGTAGACTGACTATAAATCTAGACTGAAAAAAAAG

CTTGTATTTCTTAACAGATTACCTTGTGGAACATTTGCTCCTTTCAACTAATGAGGCACTAAAT

ATTGTAACTGCTCAACTGGTGCTTTTAATTTATTTGTCTAGACTTTGTCATGTTGCCAGAAGCT

TTATCCTGGTTGGAGTTTTGAAAACAGTATTGTTTCTTCAGAAAGAAAAAAGGGATTGTCAGAT

GATCTAAAAATAAAGAAACACTGGAAATACAAGTATCCCAAGGTGATAGCATTAGGCAAGATAA

AAAT G T T GAAAAG C G AAAAAG AAC TGGTTGATAGAGAAGTGTTGTTAT

SEQ ID NO: 27306 (3Ή arm)

In an embodiment, the replacement sequence comprises or consists of a Guanine (G) residue.

In an embodiment, to correct a mutation, e.g., W1282X target site in the CFTR gene, the homology arms, e.g., the 5' and 3' homology arms, may each comprise about 1000 base pairs (bp) of sequence flanking the most distal gRNAs (e.g., 1200bp of sequence on either side of the mutation). The 5' homology arm is shown as bold sequence, the inserted base to correct the W1282X mutation is shown as lower case sequence, and the 3' homology arm is shown as no emphasis capitalized sequence.

TTTTTATTATATATTTTTGAAGTATTGATATGTAGTGAATTAGAAATTTAAAAAGAAAACAAAA CTGTCCTTCACTACAGATTGAAAAGCATTATACTAAAAGACCATTTGCTCAGTTATAGTATATA AAGGCCAAATGACTTAAAAACAAATTATGTAAGGAGAAGGAAACAACCATTTATTCAGTGCCAC TAACTGTCAGCCAGTTTTTTCAGTGGTCAGTTAATGACTGCAGTAGTGTTCTACCTTGCTCAAA GCACCCTCCTCAAGTTCTGGCATCTAAGCTGACATCAGAACACAGAGTTGGGGCTCTCTGTGGG TCACCTCTAGCACTTGATCTCCTCATGCAGTGCATGGTGCTCTCACGTCTATGCTATGTTCTTA TGGTCTTTAGGTAACAAGAATAATTTTCTTTCTTTTCCTTACTATACATTTTGCTTTCTGAAAT TCCCTTCTCGCCAATCCAGGTGAATGTCAGAATGTGATTTGACAACTGTCCAAAGTACTCATTC ACTGAGGAGTGGTAAGGCCTTCGCCCAACCTGCCTTCTCTGGGAATATACTGCTGCCTGAACAT ATCATTGTTTATTGCCAGGCTTGAACTTCACCAAATTAATTTATTAGGGTCAACATCTAAATAT

TAGAACTATTTCAGATTAATTTTTAAGTCGTATCCACTTTGGGTACTAGATCAAATTGCAGGTC

TCTGCTTCTGGCTTGAGCCTATGTTTAGAGATGATGTGCATGAAGACACTCTTTGCTTTTCCTT

TATGCAAAATGGGCATTTTCAATCTTTTTGTCATTAGTAAAGGTCAGTGATAAAGGAAGTCTGC

ATCAGGGGTCCAATTCCTTATGGCCAGTTTCTCTATTCTGTTCCAAGGTTGTTTGTCTCCATAT

ATCAACATTGGTCAGGATTGAAAGTGTGCAACAAGGTTTGAATGAATAAGTGAAAATCTTCCAC

TGGTGACAGGATAAAATATTCCAATGGTTTTTATTGAAGTACAATACTGAATTATGTTTATGGC

ATGGTACCTATATGTCACAGAAGTGATCCCATCACTTTTACCTTATAGGTGGGCCTCTTGGGAA

GAACTGGATCAGGGAAGAGTACTTTGTTATCAGCTTTTTTGAGACTACTGAACACTGAAGGAGA

AATCCAGATCGATGGTGTGTCTTGGGATTCAATAACTTTGCAACAGTGgAGGAAAGCC T T T GGA

GTGATACCACAGGTGAGCAAAAGGACTTAGCCAGAAAAAAGGCAACTAAATTATATTTTTTACT

GCTATTTGATACTTGTACTCAAGAAATTCATATTACTCTGCAAAATATATTTGTTATGCATTGC

TGTCTTTTTTCTCCAGTGCAGTTTTCTCATAGGCAGAAAAGATGTCTCTAAAAGTTTGGAATTC

TCAAATTCTGGTTATTGAAATGTTCATAGCTTTGATAGTGTTTTTCAGAAGACCAAATTTACAG

TGGGAGCCTTGGGCTTTTGTTTTTTAACAGCTCTTTTTTGTTCCTGCTTCAGTGGCCTGACCTC

CAAGTTAGCAATCGCCAGGTTGAGAAATGCTTTGCGAGACATAACAGATGCTCCTGAAATAACA

AACACTTGGAATCATGAGGTAGTGGAATTGAAAATAGAAAGTGTAGTGATTGTTTTTTGTTATT

TGGATGGGATGAACAATGTCAGATTAGTCTGTAACTATTTTTTTTTAATGTCACTCTGATTTGG

TCACAAAGGATCTCTAGTCTCATTGCCTTAGTATCATTCTACGAATTAGAATGTGTTACTGTGT

AAGAGCACTTCTTGTATATGAGAGAAATAGCAACAGTTCCAGTTTAAAGTGATATAAATGGAAA

CCAAGAAATGTCTTTACTGGGACCAAATCTGGACAGCATTTACTGTATTTTTGCTGGTATTTTC

TCTAGTCTTTCCGGGTATATTCACATTTAATGATCACTTTTCTCCCTTTGTGCTAATGGACACT

GAATCCATTCCACTACCATAGTTCTTGCTAATACTACTCTACTTTTTACACAAAATTAAAATGC

CAGGAGCACCTCCAGGTAGACTGACTATAAATCTAGACTGAAAAAAAAGCTTGTATTTCTTAAC

AGATTACCTTGTGGAACATTTGCTCCTTTCAACTAATGAGGCACTAAATATTGTAACTGCTCAA

CTGGTGCTTTTAATTTATTTGTCTAGACTTTGTCATGTTGCCAGAAGCTTTATCCTGGTTGGAG

T T T T GAAAAC AGT AT TGTTTCTT C AGAAAGAAAAAAGGGAT T GT C AGAT GAT C T AAAAAT AAAG

AAACACTGGAAATACAAGTATCCCAAGGTGATAGCATTAGGCAAGATAAAAATGTTGAAAAGCG

AAAAAG AAC TGGTTGATAGAGAAGTGTTGTTAT

(Template Construct 31; SEQ ID NO: 27307)

As described below in Table 49, shorter homology arms, e.g., 5' and/or 3' homology arms may be used. It is contemplated herein that one or both homology arms may be shortened to avoid including certain sequence repeat elements, e.g., Alu repeats, LINE elements. For example, a 5' homology arm may be shortened to avoid a sequence repeat element. In other embodiments, a 3' homology arm may be shortened to avoid a sequence repeat element. In some embodiments, both the 5' and the 3' homology arms may be shortened to avoid including certain sequence repeat elements.

In an embodiment, to correct W1282X mutation in the CFTR gene, the 5' homology arm may be shortened less than 1000 nucleotides, e.g., e.g., 500 nucleotides, to avoid inclusion of a LINE repeat element in the 5' homology arm. The 5' homology arm is shown as bold sequence, the inserted base to correct the W1282X mutation is shown as lower case sequence, and the 3' homology arm is shown as no emphasis capitalized sequence.

GGTCTCTGCTTCTGGCTTGAGCCTATGTTTAGAGATGATGTGCATGAAGACACTCTTTGCTTTT

CCTTTATGCAAAATGGGCATTTTCAATCTTTTTGTCATTAGTAAAGGTCAGTGATAAAGGAAGT

CTGCATCAGGGGTCCAATTCCTTATGGCCAGTTTCTCTATTCTGTTCCAAGGTTGTTTGTCTCC

ATATATCAACATTGGTCAGGATTGAAAGTGTGCAACAAGGTTTGAATGAATAAGTGAAAATCTT

CCACTGGTGACAGGATAAAATATTCCAATGGTTTTTATTGAAGTACAATACTGAATTATGTTTA

TGGCATGGTACCTATATGTCACAGAAGTGATCCCATCACTTTTACCTTATAGGTGGGCCTCTTG

GGAAGAACTGGATCAGGGAAGAGTACTTTGTTATCAGCTTTTTTGAGACTACTGAACACTGAAG

GAGAAATCCAGATCGATGGTGTGTCTTGGGATTCAATAACTTTGCAACAGTGgAGGAAAGCCTT

TGGAGTGATACCACAGGTGAGCAAAAGGACTTAGCCAGAAAAAAGGCAACTAAATTATATTTTT

TACTGCTATTTGATACTTGTACTCAAGAAATTCATATTACTCTGCAAAATATATTTGTTATGCA

TTGCTGTCTTTTTTCTCCAGTGCAGTTTTCTCATAGGCAGAAAAGATGTCTCTAAAAGTTTGGA

ATTCTCAAATTCTGGTTATTGAAATGTTCATAGCTTTGATAGTGTTTTTCAGAAGACCAAATTT

ACAGTGGGAGCCTTGGGCTTTTGTTTTTTAACAGCTCTTTTTTGTTCCTGCTTCAGTGGCCTGA

CCTCCAAGTTAGCAATCGCCAGGTTGAGAAATGCTTTGCGAGACATAACAGATGCTCCTGAAAT

AACAAACACTTGGAATCATGAGGTAGTGGAATTGAAAATAGAAAGTGTAGTGATTGTTTTTTGT

TATTTGGATGGGATGAACAATGTCAGATTAGTCTGTAACTA

(Template Construct 32; SEQ ID NO: 27308)

It is contemplated herein that template nucleic acids for correcting a mutation may designed for use as a single- stranded oligonucleotide (ssODN). When using a ssODN, 5' and 3' homology arms may range up to about 200 base pairs (bp) in length, e.g., at least 25, 50, 75, 100, 125, 150, 175, or 200 bp in length. Longer homology arms are also contemplated for ssODNs as improvements in oligonucleotide synthesis continue to be made.

In an embodiment, an ssODN may be used to correct a mutation, e.g., W1282X target site in the CFTR gene. For example, the ssODN may include 5' and 3' homology arms as shown below. The 5' homology arm is shown as bold sequence, the inserted bases to correct the W1282X mutation is shown as lower case sequence, and the 3' homology arm is shown as no emphasis capitalized sequence.

TTTGAGACTACTGAACACTGAAGGAGAAATCCAGATCGATGGTGTGTCTTGGGATTCAATAACT

TTGCAACAGTGgAGGAAAGCCT T TGGAGTGATACCACAGGTGAGCAAAAGGACT TAGCCAGAAA

AAAGGC AAC T AAAT T AT AT T T T

(Template Construct 33; SEQ ID NO: 27309)

In an embodiment, to correct a mutation, e.g., W1282X target site in the CFTR gene, and concomitantly introduce a silent sense mutation to disrupt subsequent Cas9 binding and cleavage, the homology arms, e.g., the 5' and 3' homology arms, may each comprise about 1000 base pairs (bp) of sequence flanking the most distal gRNAs (e.g., 1200bp of sequence on either side of the mutation). The 5' homology arm is shown as bold sequence, the inserted base to correct the W1282X mutation is shown as lower case sequence, the silent sense mutation is shown as lower case underlined and italicized sequence, and the 3' homology arm is shown as no emphasis capitalized sequence.

TTTTTATTATATATTTTTGAAGTATTGATATGTAGTGAATTAGAAATTTAAAAAGAAAACAAAA CTGTCCTTCACTACAGATTGAAAAGCATTATACTAAAAGACCATTTGCTCAGTTATAGTATATA AAGGCCAAATGACTTAAAAACAAATTATGTAAGGAGAAGGAAACAACCATTTATTCAGTGCCAC TAACTGTCAGCCAGTTTTTTCAGTGGTCAGTTAATGACTGCAGTAGTGTTCTACCTTGCTCAAA GCACCCTCCTCAAGTTCTGGCATCTAAGCTGACATCAGAACACAGAGTTGGGGCTCTCTGTGGG TCACCTCTAGCACTTGATCTCCTCATGCAGTGCATGGTGCTCTCACGTCTATGCTATGTTCTTA TGGTCTTTAGGTAACAAGAATAATTTTCTTTCTTTTCCTTACTATACATTTTGCTTTCTGAAAT TCCCTTCTCGCCAATCCAGGTGAATGTCAGAATGTGATTTGACAACTGTCCAAAGTACTCATTC ACTGAGGAGTGGTAAGGCCTTCGCCCAACCTGCCTTCTCTGGGAATATACTGCTGCCTGAACAT ATCATTGTTTATTGCCAGGCTTGAACTTCACCAAATTAATTTATTAGGGTCAACATCTAAATAT TAGAACTATTTCAGATTAATTTTTAAGTCGTATCCACTTTGGGTACTAGATCAAATTGCAGGTC TCTGCTTCTGGCTTGAGCCTATGTTTAGAGATGATGTGCATGAAGACACTCTTTGCTTTTCCTT TATGCAAAATGGGCATTTTCAATCTTTTTGTCATTAGTAAAGGTCAGTGATAAAGGAAGTCTGC

ATCAGGGGTCCAATTCCTTATGGCCAGTTTCTCTATTCTGTTCCAAGGTTGTTTGTCTCCATAT

ATCAACATTGGTCAGGATTGAAAGTGTGCAACAAGGTTTGAATGAATAAGTGAAAATCTTCCAC

TGGTGACAGGATAAAATATTCCAATGGTTTTTATTGAAGTACAATACTGAATTATGTTTATGGC

ATGGTACCTATATGTCACAGAAGTGATCCCATCACTTTTACCTTATAGGTGGGCCTCTTGGGAA

GAACTGGATCAGGGAAGAGTACTTTGTTATCAGCTTTTTTGAGACTACTGAACACTGAAGGAGA

AATCCAGATCGATGGTGTGTCTTGGGATTCAATAACTTTGCAACAGTGgAG a AAAGCC T T T GGA

GTGATACCACAGGTGAGCAAAAGGACTTAGCCAGAAAAAAGGCAACTAAATTATATTTTTTACT

GCTATTTGATACTTGTACTCAAGAAATTCATATTACTCTGCAAAATATATTTGTTATGCATTGC

TGTCTTTTTTCTCCAGTGCAGTTTTCTCATAGGCAGAAAAGATGTCTCTAAAAGTTTGGAATTC

TCAAATTCTGGTTATTGAAATGTTCATAGCTTTGATAGTGTTTTTCAGAAGACCAAATTTACAG

TGGGAGCCTTGGGCTTTTGTTTTTTAACAGCTCTTTTTTGTTCCTGCTTCAGTGGCCTGACCTC

CAAGTTAGCAATCGCCAGGTTGAGAAATGCTTTGCGAGACATAACAGATGCTCCTGAAATAACA

AACACTTGGAATCATGAGGTAGTGGAATTGAAAATAGAAAGTGTAGTGATTGTTTTTTGTTATT

TGGATGGGATGAACAATGTCAGATTAGTCTGTAACTATTTTTTTTTAATGTCACTCTGATTTGG

TCACAAAGGATCTCTAGTCTCATTGCCTTAGTATCATTCTACGAATTAGAATGTGTTACTGTGT

AAGAGCACTTCTTGTATATGAGAGAAATAGCAACAGTTCCAGTTTAAAGTGATATAAATGGAAA

CCAAGAAATGTCTTTACTGGGACCAAATCTGGACAGCATTTACTGTATTTTTGCTGGTATTTTC

TCTAGTCTTTCCGGGTATATTCACATTTAATGATCACTTTTCTCCCTTTGTGCTAATGGACACT

GAATCCATTCCACTACCATAGTTCTTGCTAATACTACTCTACTTTTTACACAAAATTAAAATGC

CAGGAGCACCTCCAGGTAGACTGACTATAAATCTAGACTGAAAAAAAAGCTTGTATTTCTTAAC

AGATTACCTTGTGGAACATTTGCTCCTTTCAACTAATGAGGCACTAAATATTGTAACTGCTCAA

CTGGTGCTTTTAATTTATTTGTCTAGACTTTGTCATGTTGCCAGAAGCTTTATCCTGGTTGGAG

T T T T GAAAAC AGT AT TGTTTCTT C AGAAAGAAAAAAGGGAT T GT C AGAT GAT C T AAAAAT AAAG

AAACACTGGAAATACAAGTATCCCAAGGTGATAGCATTAGGCAAGATAAAAATGTTGAAAAGCG

AAAAAG AAC TGGTTGATAGAGAAGTGTTGTTAT

(Template Construct 34; SEQ ID NO: 27310)

In an embodiment, to correct a mutation, e.g., W1282X target site in the CFTR gene, and concomitantly introduce a silent mutation to disrupt subsequent Cas9 binding and cleavage, the 5' homology arm may be shortened less than 750 nucleotides, e.g., 500 nucleotides, to avoid inclusion of a LINE repeat element in the 5' homology arm. The 5' homology arm is shown as bold sequence, the inserted base to correct the W1282X mutation is shown as lower case sequence, the silent sense mutation is shown as lower case underlined and italicized sequence, and the 3' homology arm is shown as no emphasis capitalized sequence.

GGTCTCTGCTTCTGGCTTGAGCCTATGTTTAGAGATGATGTGCATGAAGACACTCTTTGCTTTT CCTTTATGCAAAATGGGCATTTTCAATCTTTTTGTCATTAGTAAAGGTCAGTGATAAAGGAAGT CTGCATCAGGGGTCCAATTCCTTATGGCCAGTTTCTCTATTCTGTTCCAAGGTTGTTTGTCTCC ATATATCAACATTGGTCAGGATTGAAAGTGTGCAACAAGGTTTGAATGAATAAGTGAAAATCTT CCACTGGTGACAGGATAAAATATTCCAATGGTTTTTATTGAAGTACAATACTGAATTATGTTTA TGGCATGGTACCTATATGTCACAGAAGTGATCCCATCACTTTTACCTTATAGGTGGGCCTCTTG GGAAGAACTGGATCAGGGAAGAGTACTTTGTTATCAGCTTTTTTGAGACTACTGAACACTGAAG GAGAAATCCAGATCGATGGTGTGTCTTGGGATTCAATAACTTTGCAACAGTGgAGaAAAGCCTT TGGAGTGATACCACAGGTGAGCAAAAGGACTTAGCCAGAAAAAAGGCAACTAAATTATATTTTT TACTGCTATTTGATACTTGTACTCAAGAAATTCATATTACTCTGCAAAATATATTTGTTATGCA TTGCTGTCTTTTTTCTCCAGTGCAGTTTTCTCATAGGCAGAAAAGATGTCTCTAAAAGTTTGGA ATTCTCAAATTCTGGTTATTGAAATGTTCATAGCTTTGATAGTGTTTTTCAGAAGACCAAATTT ACAGTGGGAGCCTTGGGCTTTTGTTTTTTAACAGCTCTTTTTTGTTCCTGCTTCAGTGGCCTGA CCTCCAAGTTAGCAATCGCCAGGTTGAGAAATGCTTTGCGAGACATAACAGATGCTCCTGAAAT AACAAACACTTGGAATCATGAGGTAGTGGAATTGAAAATAGAAAGTGTAGTGATTGTTTTTTGT TATTTGGATGGGATGAACAATGTCAGATTAGTCTGTAACTA

In an embodiment, an ssODN may be to correct a mutation, e.g., W1282X target site in the CFTR gene, and concomitantly introduce a silent mutation to disrupt subsequent Cas9 binding and cleavage. For example, the ssODN may include 5' and 3' homology arms as shown below. The 5' homology arm is shown as bold sequence, the inserted base to correct the W1282X mutation is shown as lower case sequence, the silent sense mutation is shown as lower case underlined and italicized sequence, and the 3' homology arm is shown as no emphasis capitalized sequence.

TTTGAGACTACTGAACACTGAAGGAGAAATCCAGATCGATGGTGTGTCTTGGGATTCAATAACT

TTGCAACAGTGgAGaAAAGCCTTTGGAGTGATACCACAGGTGAGCAAAAGGACTTAGCCAGAAA

AAAGGC AAC T AAAT T AT AT T T T

(Template Construct 35; SEQ ID NO: 27311) The underlined A has been changed from a T to A at that position so that wild-type CFTR is still transcribed, but the PAM sequence AGG has been modified to reduce or eliminate Cas9 cleavage at that locus.

Exemplary template nucleic acids (also referred to herein as donor constructs) to correction a mutation, e.g., R553X target site in the CFTR gene, are provided.

Suitable sequence for the 5' homology arm can be selected from (e.g., includes a portion of) or include the following sequence:

AACAGAAGTAACCATTTTGATACTTTAGATATAGATAATATTGGATTATTTCTGGATTGTGAAA

GAAGAAGGAAGAAGCATATGGAAGAGAAGTTTTAGTAGAGGGGAGGAAGGAGGAGGTGGAAACG

AAT GT AC AAGGAT GGGAGGAGAAAAGGGAGAGAGAC TTTTTTTTTTT T AAGGCGAGAGT T T AC T

ACCTATCTAACTCTTCGCATTCTTGAAGTCTCAGACCAAATCCCATCGGTTTGAAAGCCTCTAG

GGTATTCTATCTATTGTATACTTCTGTTATGTACAAAATTAATTTGCCAATTAATTGTGAACTG

TTTTATAAACTATCTTAAAATGGTTAGTTAAATCTTTGGGATAGTATTTAGCTTTCTCCAGGAT

TATGACTTACCTTCTAAATTAGACATACAATGCCTAGGAGTCAAGGACTATTTTGCATAAATTC

CAGTCTTCTTTTACAATGCCTAGAATGATTGTTACCACAGAAATATTCATTACCTGGGAGAAAG

GATGACAGGAGGGGCAGAATGAATGGAGAGAGGTCGTGAGAATGAGGTGCTGAGGATGGACGAG

GAAGAAAGCTGTTTTAGTTGGGAGGATAGGTGACAGAAGCATGGAAAGGAATTGCCTTGGACCC

ATGGAAGCCCAGTGAAGATACTTAGATCCTGCAGGGGTGTGAATAATGTTCTTTTAGTTTCTCT

TCTTAGGAGGTTTGTTCATTTTGGGAGATTTCTTTTGAAAAGAGTGAACTTAAATTGGAGAAAA

GTACATTTTAGTATGTTGATAACATTTGAATTTGTAAAATGGACCTATGGATGATCTACACATA

TTTATATACCCATAAATATACACATATTTTAATTTTTGGTATTTTATAATTATTATTTAATGAT

CATTCATGACATTTTAAAAATTACAGAAAAATTTACATCTAAAATTTCAGCAATGTTGTTTTTG

ACCAACTAAATAAATTGCATTTGAAATAATGGAGATGCAATGTTCAAAATTTCAACTGTGGTTA

AAGCAATAGTGTGATATATGATTACATTAGAAGGAAGATGTGCCTTTCAAATTCAGATTGAGCA

TACTAAAAGTGACTCTCTAATTTTCTATTTTTGGTAATAGGACATCTCCAAGTTTGCAGAGAAA

GAC AAT AT AGT T C T T GGAGAAGGT GGAAT C AC AC T GAGT GGAGGT C AA

SEQ ID NO: 27312 (5Ή arm)

Suitable sequence for the 3' homology arm can be selected from (e.g., includes a portion of) or include the following sequence:

GAGCAAGAATTTCTTTAGCAAGGTGAATAACTAATTATTGGTCTAGCAAGCATTTGCTGTAAAT GTCATTCATGTAAAAAAATTACAGACATTTCTCTATTGCTTTATATTCTGTTTCTGGAATTGAA AAAATCCTGGGGTTTTATGGCTAGTGGGTTAAGAATCACATTTAAGAACTATAAATAATGGTAT

AGTATCCAGATTTGGTAGAGATTATGGTTACTCAGAATCTGTGCCCGTATCTTGGTGTCAGTGT

ATTTGTTTGCCTCATAGTATAGTTTACTACAAATGGAAAACTCTAGGATTCTGCATAATACTGG

ACAGAGAAGATGTAAATATCTGTTAGTTCCATCATAGACCCTGCCACTCCAATGTACACACCAG

CTTTAGGCTTCTTGGTATAGATAAACATACATTTTCAAAATTTTTCATCATAATTTTCATAACA

AAATAGGAAGGCAAATGATGTCACTTGGCTTAAAATCTATAATATTTAAAATAAACAGGACAAA

TGCATTAACATTGTTGGGGGAGGAGGTCCCTTAGTAGAAACACTCTTGGTCCAAGCATTTTAAA

GCTGTCAAAGAGATGTAAATATAGATAATGTATGTCAAGGAGAGAGCTTTGTGGTTAAACTGTA

ACTTTCAGTTTAAACAATTATTGGTGACTCTGATGTCAAATGTTTCTCAAGCTTTATCTGAACA

AAATTCTTCTCACTTTGTTGCCAAAGTCGTTAACAAGAAATCACATTGACTCATTGATGTTTTG

GCTCCTTTCCCTTACTTTCTGTTGCTTTCCAAAAGCTGAGACAGGAAACTAACCCTAACTGAGC

ACCTGCAATTGCCTGGTAGTATTCTAGTCATGTGTGTACTTTTGTGTGTATGTAATCCCCTTAC

AGCTCTGCAAAGTAAGAATTGTTCTCCCTGCTTTACAGAAGAGATCATAAGATAATTGAGGCTG

TTAGATGTTAACTTGCCAAAAGCCATACAGGAAAATGGTAGAGTCACAGTTTGAACCAGGTCCT

TTTGATTCTTTACATTAAACCATGCTTTGATCTTGGAAATACACTGTAAGGCAATAAATCAATA

GATACGGATAATTCACAGGCTTCTAAATAAATGGAAGTTGATTGTTTTTATCTGTGAGCCAAAG

TAAGAC T T AT T CTAAGAAT T CC AC AAAT T T AGAT AAGAT AGAGT AT AT

SEQ ID NO: 27313 (3 Ή arm)

In an embodiment, the replacement sequence comprises or consists of a Cytosine (C) residue.

In an embodiment, to correct a mutation, e.g., R553X target site in the CFTR gene, the homology arms, e.g., the 5' and 3' homology arms, may each comprise about 1000 base pairs (bp) of sequence flanking the most distal gRNAs (e.g., 1200bp of sequence on either side of the mutation). The 5' homology arm is shown as bold sequence, the inserted base to correct the R553X mutation is shown as lower case sequence, and the 3' homology arm is shown as no emphasis capitalized sequence.

AACAGAAGTAACCATTTTGATACTTTAGATATAGATAATATTGGATTATTTCTGGATTGTGAAA GAAGAAGGAAGAAGCATATGGAAGAGAAGTTTTAGTAGAGGGGAGGAAGGAGGAGGTGGAAACG AATGTACAAGGATGGGAGGAGAAAAGGGAGAGAGACTTTTTTTTTTTTAAGGCGAGAGTTTACT ACCTATCTAACTCTTCGCATTCTTGAAGTCTCAGACCAAATCCCATCGGTTTGAAAGCCTCTAG GGTATTCTATCTATTGTATACTTCTGTTATGTACAAAATTAATTTGCCAATTAATTGTGAACTG TTTTATAAACTATCTTAAAATGGTTAGTTAAATCTTTGGGATAGTATTTAGCTTTCTCCAGGAT TATGACTTACCTTCTAAATTAGACATACAATGCCTAGGAGTCAAGGACTATTTTGCATAAATTC CAGTCTTCTTTTACAATGCCTAGAATGATTGTTACCACAGAAATATTCATTACCTGGGAGAAAG GATGACAGGAGGGGCAGAATGAATGGAGAGAGGTCGTGAGAATGAGGTGCTGAGGATGGACGAG GAAGAAAGCTGTTTTAGTTGGGAGGATAGGTGACAGAAGCATGGAAAGGAATTGCCTTGGACCC ATGGAAGCCCAGTGAAGATACTTAGATCCTGCAGGGGTGTGAATAATGTTCTTTTAGTTTCTCT TCTTAGGAGGTTTGTTCATTTTGGGAGATTTCTTTTGAAAAGAGTGAACTTAAATTGGAGAAAA GTACATTTTAGTATGTTGATAACATTTGAATTTGTAAAATGGACCTATGGATGATCTACACATA TTTATATACCCATAAATATACACATATTTTAATTTTTGGTATTTTATAATTATTATTTAATGAT CATTCATGACATTTTAAAAATTACAGAAAAATTTACATCTAAAATTTCAGCAATGTTGTTTTTG ACCAACTAAATAAATTGCATTTGAAATAATGGAGATGCAATGTTCAAAATTTCAACTGTGGTTA AAGCAATAGTGTGATATATGATTACATTAGAAGGAAGATGTGCCTTTCAAATTCAGATTGAGCA TACTAAAAGTGACTCTCTAATTTTCTATTTTTGGTAATAGGACATCTCCAAGTTTGCAGAGAAA GACAATATAGTTCTTGGAGAAGGTGGAATCACACTGAGTGGAGGTCAAc GAGCAAGAAT T T C T T TAGCAAGGTGAATAACTAATTATTGGTCTAGCAAGCATTTGCTGTAAATGTCATTCATGTAAAA AAATTACAGACATTTCTCTATTGCTTTATATTCTGTTTCTGGAATTGAAAAAATCCTGGGGTTT TATGGCTAGTGGGTTAAGAATCACATTTAAGAACTATAAATAATGGTATAGTATCCAGATTTGG TAGAGATTATGGTTACTCAGAATCTGTGCCCGTATCTTGGTGTCAGTGTATTTGTTTGCCTCAT AGTATAGTTTACTACAAATGGAAAACTCTAGGATTCTGCATAATACTGGACAGAGAAGATGTAA ATATCTGTTAGTTCCATCATAGACCCTGCCACTCCAATGTACACACCAGCTTTAGGCTTCTTGG T AT AGAT AAAC AT AC AT T T T CAAAAT T T T T CAT C AT AAT T T T C AT AAC AAAAT AGGAAGGC AAA TGATGTCACTTGGCTTAAAATCTATAATATTTAAAATAAACAGGACAAATGCATTAACATTGTT GGGGGAGGAGGTCCCTTAGTAGAAACACTCTTGGTCCAAGCATTTTAAAGCTGTCAAAGAGATG TAAAT AT AGAT AATGTATGTCAAGGAGAGAGCTTTGTGGTTAAACTGTAACTTTCAGTTT AAAC AATTATTGGTGACTCTGATGTCAAATGTTTCTCAAGCTTTATCTGAACAAAATTCTTCTCACTT TGTTGCCAAAGTCGTTAACAAGAAATCACATTGACTCATTGATGTTTTGGCTCCTTTCCCTTAC TTTCTGTTGCTTTCCAAAAGCTGAGACAGGAAACTAACCCTAACTGAGCACCTGCAATTGCCTG GTAGTATTCTAGTCATGTGTGTACTTTTGTGTGTATGTAATCCCCTTACAGCTCTGCAAAGTAA GAATTGTTCTCCCTGCTTTACAGAAGAGATCATAAGATAATTGAGGCTGTTAGATGTTAACTTG CCAAAAGCCATACAGGAAAATGGTAGAGTCACAGTTTGAACCAGGTCCTTTTGATTCTTTACAT TAAACCATGCTTTGATCTTGGAAATACACTGTAAGGCAATAAATCAAT AGAT ACGGAT AAT TCA CAGGCTTCTAAATAAATGGAAGTTGATTGTTTTTATCTGTGAGCCAAAGTAAGACTTATTCTAA GAAT T CC AC AAAT T T AGAT AAGAT AGAGT AT AT

(Template Construct 36; SEQ ID NO: 27314)

As described below in Table 49, shorter homology arms, e.g., 5' and/or 3' homology arms may be used.

It is contemplated herein that one or both homology arms may be shortened to avoid including certain sequence repeat elements, e.g., Alu repeats, LINE elements. For example, a 5' homology arm may be shortened to avoid a sequence repeat element. In other embodiments, a 3' homology arm may be shortened to avoid a sequence repeat element. In some embodiments, both the 5' and the 3' homology arms may be shortened to avoid including certain sequence repeat elements.

In an embodiment, to correct R553X mutation in the CFTR gene, the 5' homology arm may be shortened less than 1000 nucleotides, e.g., e.g., 500 nucleotides, to avoid inclusion of a LINE repeat element in the 5' homology arm. The 5' homology arm is shown as bold sequence, the inserted base to correct the R553X mutation is shown as lower case sequence, and the 3' homology arm is shown as no emphasis capitalized sequence.

CTCTTCTTAGGAGGTTTGTTCATTTTGGGAGATTTCTTTTGAAAAGAGTGAACTTAAATTGGAG AAAAGTACATTTTAGTATGTTGATAACATTTGAATTTGTAAAATGGACCTATGGATGATCTACA CATATTTATATACCCATAAATATACACATATTTTAATTTTTGGTATTTTATAATTATTATTTAA TGATCATTCATGACATTTTAAAAATTACAGAAAAATTTACATCTAAAATTTCAGCAATGTTGTT TTTGACCAACTAAATAAATTGCATTTGAAATAATGGAGATGCAATGTTCAAAATTTCAACTGTG GTTAAAGCAATAGTGTGATATATGATTACATTAGAAGGAAGATGTGCCTTTCAAATTCAGATTG AGCATACTAAAAGTGACTCTCTAATTTTCTATTTTTGGTAATAGGACATCTCCAAGTTTGCAGA GAAAGACAATATAGTTCTTGGAGAAGGTGGAATCACACTGAGTGGAGGTCAAcGAGCAAGAATT TCTTTAGCAAGGTGAATAACTAATTATTGGTCTAGCAAGCATTTGCTGTAAATGTCATTCATGT AAAAAAATTACAGACATTTCTCTATTGCTTTATATTCTGTTTCTGGAATTGAAAAAATCCTGGG GTTTTATGGCTAGTGGGTTAAGAATCACATTTAAGAACTATAAATAATGGTATAGTATCCAGAT TTGGTAGAGATTATGGTTACTCAGAATCTGTGCCCGTATCTTGGTGTCAGTGTATTTGTTTGCC TCATAGTATAGTTTACTACAAATGGAAAACTCTAGGATTCTGCATAATACTGGACAGAGAAGAT GTAAATATCTGTTAGTTCCATCATAGACCCTGCCACTCCAATGTACACACCAGCTTTAGGCTTC T TGGTATAGATAAACATACAT T T TCAAAAT T T T TCATCATAAT T T TCATAACAAAATAGGAAGG

CAAATGATGTCACT TGGCT TAAAATCTATAATAT T TAAAAT

(Template Construct 37; SEQ ID NO: 27315)

It is contemplated herein that template nucleic acids for correcting a mutation may designed for use as a single- stranded oligonucleotide (ssODN). When using a ssODN, 5' and 3' homology arms may range up to about 200 base pairs (bp) in length, e.g., at least 25, 50, 75, 100, 125, 150, 175, or 200 bp in length. Longer homology arms are also contemplated for ssODNs as improvements in oligonucleotide synthesis continue to be made.

In an embodiment, an ssODN may be used to correct a mutation, e.g., R553X target site in the CFTR gene. For example, the ssODN may include 5' and 3' homology arms as shown below. The 5' homology arm is shown as bold sequence, the inserted bases to correct the R553X mutation is shown as lower case sequence, and the 3' homology arm is shown as no emphasis capitalized sequence.

TAGGACATCTCCAAGTTTGCAGAGAAAGACAATATAGTTCTTGGAGAAGGTGGAATCACACTGA

GTGGAGGTCAAcGAGCAAGAAT T TCT T TAGCAAGGTGAATAACTAAT TAT TGGTCTAGCAAGCA

T T TGCTGTAAATGTCAT TCATGT

(Template Construct 38; SEQ ID NO: 27316)

In an embodiment, to correct a mutation, e.g., R553X target site in the CFTR gene, and concomitantly introduce a silent sense mutation to disrupt subsequent Cas9 binding and cleavage, the homology arms, e.g., the 5' and 3' homology arms, may each comprise about 1000 base pairs (bp) of sequence flanking the most distal gRNAs (e.g., 1200bp of sequence on either side of the mutation). The 5' homology arm is shown as bold sequence, the inserted base to correct the R553X mutation is shown as lower case sequence, the silent sense mutation is shown as lower case underlined and italicized sequence, and the 3' homology arm is shown as no emphasis capitalized sequence.

AACAGAAGTAACCATTTTGATACTTTAGATATAGATAATATTGGATTATTTCTGGATTGTGAAA GAAGAAGGAAGAAGCATATGGAAGAGAAGTTTTAGTAGAGGGGAGGAAGGAGGAGGTGGAAACG AATGTACAAGGATGGGAGGAGAAAAGGGAGAGAGACTTTTTTTTTTTTAAGGCGAGAGTTTACT ACCTATCTAACTCTTCGCATTCTTGAAGTCTCAGACCAAATCCCATCGGTTTGAAAGCCTCTAG GGTATTCTATCTATTGTATACTTCTGTTATGTACAAAATTAATTTGCCAATTAATTGTGAACTG TTTTATAAACTATCTTAAAATGGTTAGTTAAATCTTTGGGATAGTATTTAGCTTTCTCCAGGAT TATGACTTACCTTCTAAATTAGACATACAATGCCTAGGAGTCAAGGACTATTTTGCATAAATTC CAGTCTTCTTTTACAATGCCTAGAATGATTGTTACCACAGAAATATTCATTACCTGGGAGAAAG GATGACAGGAGGGGCAGAATGAATGGAGAGAGGTCGTGAGAATGAGGTGCTGAGGATGGACGAG GAAGAAAGCTGTTTTAGTTGGGAGGATAGGTGACAGAAGCATGGAAAGGAATTGCCTTGGACCC ATGGAAGCCCAGTGAAGATACTTAGATCCTGCAGGGGTGTGAATAATGTTCTTTTAGTTTCTCT TCTTAGGAGGTTTGTTCATTTTGGGAGATTTCTTTTGAAAAGAGTGAACTTAAATTGGAGAAAA GTACATTTTAGTATGTTGATAACATTTGAATTTGTAAAATGGACCTATGGATGATCTACACATA TTTATATACCCATAAATATACACATATTTTAATTTTTGGTATTTTATAATTATTATTTAATGAT CATTCATGACATTTTAAAAATTACAGAAAAATTTACATCTAAAATTTCAGCAATGTTGTTTTTG ACCAACTAAATAAATTGCATTTGAAATAATGGAGATGCAATGTTCAAAATTTCAACTGTGGTTA AAGCAATAGTGTGATATATGATTACATTAGAAGGAAGATGTGCCTTTCAAATTCAGATTGAGCA TACTAAAAGTGACTCTCTAATTTTCTATTTTTGGTAATAGGACATCTCCAAGTTTGCAGAGAAA GACAATATAGTTCTTGGAGAAGGTGGAATCACACTGt caGGAGGTCAAc GAGCAAGAAT T T C T T TAGCAAGGTGAATAACTAATTATTGGTCTAGCAAGCATTTGCTGTAAATGTCATTCATGTAAAA AAATTACAGACATTTCTCTATTGCTTTATATTCTGTTTCTGGAATTGAAAAAATCCTGGGGTTT TATGGCTAGTGGGTTAAGAATCACATTTAAGAACTATAAATAATGGTATAGTATCCAGATTTGG TAGAGATTATGGTTACTCAGAATCTGTGCCCGTATCTTGGTGTCAGTGTATTTGTTTGCCTCAT AGTATAGTTTACTACAAATGGAAAACTCTAGGATTCTGCATAATACTGGACAGAGAAGATGTAA ATATCTGTTAGTTCCATCATAGACCCTGCCACTCCAATGTACACACCAGCTTTAGGCTTCTTGG T AT AGAT AAAC AT AC AT T T T CAAAAT T T T T CAT C AT AAT T T T C AT AAC AAAAT AGGAAGGC AAA TGATGTCACTTGGCTTAAAATCTATAATATTTAAAATAAACAGGACAAATGCATTAACATTGTT GGGGGAGGAGGTCCCTTAGTAGAAACACTCTTGGTCCAAGCATTTTAAAGCTGTCAAAGAGATG TAAAT AT AGAT AATGTATGTCAAGGAGAGAGCTTTGTGGTTAAACTGTAACTTTCAGTTT AAAC AATTATTGGTGACTCTGATGTCAAATGTTTCTCAAGCTTTATCTGAACAAAATTCTTCTCACTT TGTTGCCAAAGTCGTTAACAAGAAATCACATTGACTCATTGATGTTTTGGCTCCTTTCCCTTAC TTTCTGTTGCTTTCCAAAAGCTGAGACAGGAAACTAACCCTAACTGAGCACCTGCAATTGCCTG GTAGTATTCTAGTCATGTGTGTACTTTTGTGTGTATGTAATCCCCTTACAGCTCTGCAAAGTAA GAATTGTTCTCCCTGCTTTACAGAAGAGATCATAAGATAATTGAGGCTGTTAGATGTTAACTTG CCAAAAGCCATACAGGAAAATGGTAGAGTCACAGTTTGAACCAGGTCCTTTTGATTCTTTACAT TAAACCATGCTTTGATCTTGGAAATACACTGTAAGGCAATAAATCAAT AGAT ACGGAT AAT TCA CAGGCTTCTAAATAAATGGAAGTTGATTGTTTTTATCTGTGAGCCAAAGTAAGACTTATTCTAA GAAT T CC AC AAAT T T AGAT AAGAT AGAGT AT AT (Template Construct 39; SEQ ID NO: 27317)

In an embodiment, to correct a mutation, e.g., R553X target site in the CFTR gene, and concomitantly introduce a silent mutation to disrupt subsequent Cas9 binding and cleavage, the 5' homology arm may be shortened less than 750 nucleotides, e.g., 500 nucleotides, to avoid inclusion of a LINE repeat element in the 5' homology arm. The 5' homology arm is shown as bold sequence, the inserted base to correct the R553X mutation is shown as lower case sequence, the silent sense mutation is shown as lower case underlined and italicized sequence, and the 3' homology arm is shown as no emphasis capitalized sequence.

CTCTTCTTAGGAGGTTTGTTCATTTTGGGAGATTTCTTTTGAAAAGAGTGAACTTAAATTGGAG

AAAAGTACATTTTAGTATGTTGATAACATTTGAATTTGTAAAATGGACCTATGGATGATCTACA

CATATTTATATACCCATAAATATACACATATTTTAATTTTTGGTATTTTATAATTATTATTTAA

TGATCATTCATGACATTTTAAAAATTACAGAAAAATTTACATCTAAAATTTCAGCAATGTTGTT

TTTGACCAACTAAATAAATTGCATTTGAAATAATGGAGATGCAATGTTCAAAATTTCAACTGTG

GTTAAAGCAATAGTGTGATATATGATTACATTAGAAGGAAGATGTGCCTTTCAAATTCAGATTG

AGCATACTAAAAGTGACTCTCTAATTTTCTATTTTTGGTAATAGGACATCTCCAAGTTTGCAGA

GAAAGACAATATAGTTCTTGGAGAAGGTGGAATCACACTGt caGGAGGTCAAcGAGCAAGAAT T

TCTTTAGCAAGGTGAATAACTAATTATTGGTCTAGCAAGCATTTGCTGTAAATGTCATTCATGT

AAAAAAATTACAGACATTTCTCTATTGCTTTATATTCTGTTTCTGGAATTGAAAAAATCCTGGG

GTTTTATGGCTAGTGGGTTAAGAATCACATTTAAGAACTATAAATAATGGTATAGTATCCAGAT

TTGGTAGAGATTATGGTTACTCAGAATCTGTGCCCGTATCTTGGTGTCAGTGTATTTGTTTGCC

TCATAGTATAGTTTACTACAAATGGAAAACTCTAGGATTCTGCATAATACTGGACAGAGAAGAT

GTAAATATCTGTTAGTTCCATCATAGACCCTGCCACTCCAATGTACACACCAGCTTTAGGCTTC

TTGGTATAGATAAACATACATTTTCAAAATTTTTCATCATAATTTTCATAACAAAATAGGAAGG

CAAATGATGTCACTTGGCTTAAAATCTATAATATTTAAAAT

(Template Construct 40; SEQ ID NO: 27318)

In an embodiment, an ssODN may be to correct a mutation, e.g., R553X target site in the CFTR gene, and concomitantly introduce a silent mutation to disrupt subsequent Cas9 binding and cleavage. For example, the ssODN may include 5' and 3' homology arms as shown below. The 5' homology arm is shown as bold sequence, the inserted base to correct the R553X mutation is shown as lower case sequence, the silent sense mutation is shown as lower case underlined and italicized sequence, and the 3' homology arm is shown as no emphasis capitalized sequence.

TAGGACATCTCCAAGTTTGCAGAGAAAGACAATATAGTTCTTGGAGAAGGTGGAATCACACTGt caGGAGGTCAAcGAGCAAGAATTTCTTTAGCAAGGTGAATAACTAATTATTGGTCTAGCAAGCA

TTTGCTGTAAATGTCATTCATGT

(Template Construct 41; SEQ ID NO: 27319)

The underlined T has been changed from an A to T at that position, the underlined C has been changed from a G to C at that position, and the underlined A has been changed from a T to A at that position, so that wild-type CFTR is still transcribed, but the PAM sequence AGG has been modified to reduce or eliminate Cas9 cleavage at that locus.

Exemplary template nucleic acids (also referred to herein as donor constructs) to correction a mutation, e.g., an intronic 2789+5bp (G-^A) target site in the CFTR gene, are provided.

Suitable sequence for the 5' homology arm can be selected from (e.g., includes a portion of) or include the following sequence:

TTTTTCTGTTTCATTCTGTGGTAAAGGTATCATTTGGCTAATTGTATAATTTCAGTGTCATTTC TAATATTCCAATTGTGATAGTATCAACACAAGATTAAATTTCTCTACATGGTTTATGAGAATGG AATGCCAAATTGAAATAGAACAGAGCACAGATGATCTAAATATAAAAAGAACTACAAAAATCAC AGTTGTTTAAAAAGGTTTTTTGTTTGTTTATATATGGTGCAGAACATTTGTTCCTTAGCCAAAT GTTTCCACCTTGAGAAAGCTATAGAGATTCTATGTAGTCCTAGTACCAATAATATGTTTTAACC TGAATGTACCTTATCTTTATTCATAAACTGTGACTTTTTACACTGCTGAAACTTTTTTTTTTAA GACAATCTCACTCTGTCGTCCAGTCTGGAGTGCAGCAGTGGTGTGATCTTGGCTCACTGCAACC TCTACCTTCTGTGTTCAAGCAATTCTGGTGCCTCGGCCACCTGAGTAGTTGGGATCACAGGTGT ACACCACCAGGCCTGGCTAATAGTTTTTGATATTTCTAGTAGAGATGAGTTTTGCCACATTGGC CAGGCTGGCCTGAAACTCCTGGCCTCAAGTGATCTGCCTGCCTTGGCCTCCCAAAGTGTTGGTA TTACAAGTGTGAGCCACTGTGCCTGGCCTGAAACTCATAATTCATTTCCATTAATATTAATCTC ACCTTTTCCAATAATTAATTGATTTCACAAGTATTAGTCCCCTATAATCATTGAATGGCTAATA AAATTATTTATAGCAAACAGATTAATTATCTGCCAGCAGTCTGAGATTAGTTTCTTTAAAAAAT GTTTATTATTTAAAACATTCAGCTGTGATCTTGGCTTTCTTGTGAGGTTCAATAGTTTCTATTG AGTAAAGGAGAGAAATGGCAGAGAATTTACTTCAGTGAAATTTGAATTCCATTAACTTAATGTG GTCTCATCACAAATAATAGTACTTAGAACACCTAGTACAGCTGCTGGACCCAGGAACACAAAGC AAAGGAAGATGAAATTGTGTGTACCTTGATATTGGTACACACATCAAATGGTGTGATGTGAATT TAGATGTGGGCATGGGAGGAATAGGTGAAGATGTTAGAAAAAAAATCAACTGTGTCTTGTTCCA TTCCAGGTGGCTGCTTCTTTGGTTGTGCTGTGGCTCCTTGGAAAGTGA SEQ ID NO: 27320 (5Ή arm)

Suitable sequence for the 3' homology arm can be selected from (e.g., includes a portion of) or include the following sequence:

TATTCCATGTCCTATTGTGTAGATTGTGTTTTATTTCTGTTGATTAAATATTGTAATCCACTAT

GTTTGTATGTATTGTAATCCACTTTGTTTCATTTCTCCCAAGCATTATGGTAGTGGAAAGATAA

GGTTTTTTGTTTAAATGATGACCATTAGTTGGGTGAGGTGACACATTCCTGTAGTCCTAGCTCC

TCCACAGGCTGACGCAGGAGGATCACTTGAGCCCAGGAGTTCAGGGCTGTAGTGTTGTATCATT

GTGAGTAGCCACCGCACTCCAGCCTGGACAATATAGTGAGATCCTATATCTAAAATAAAATAAA

ATAAAATGAATAAATTGTGAGCATGTGCAGCTCCTGCAGTTTCTAAAGAATATAGTTCTGTTCA

GTTTCTGTGAAACACAATAAAAATATTTGAAATAACATTACATATTTAGGGTTTTCTTCAAATT

TTTTAATTTAATAAAGAACAACTCAATCTCTATCAATAGTGAGAAAACATATCTATTTTCTTGC

AATAATAGTATGATTTTGAGGTTAAGGGTGCATGCTCTTCTAATGCAAAATATTGTATTTATTT

AGACTCAAGTTTAGTTCCATTTACATGTATTGGAAATTCAGTAAGTAACTTTGGCTGCCAAATA

ACGATTTCCTATTTGCTTTACAGCACTCCTCTTCAAGACAAAGGGAATAGTACTCATAGTAGAA

ATAACAGCTATGCAGTGATTATCACCAGCACCAGTTCGTATTATGTGTTTTACATTTACGTGGG

AGTAGCCGACACTTTGCTTGCTATGGGATTCTTCAGAGGTCTACCACTGGTGCATACTCTAATC

ACAGTGTCGAAAATTTTACACCACAAAATGTTACATTCTGTTCTTCAAGCACCTATGTCAACCC

TCAACACGTTGAAAGCAGGTACTTTACTAGGTCTAAGAAATGAAACTGCTGATCCACCATCAAT

AGGGCCTGTGGTTTTGTTGGTTTTCTAATGGCAGTGCTGGCTTTTGCACAGAGGCATGTGCCCT

TTGTTGAACCTCCATTTGACTGGCATGCACATGTCTCAGATATTATAGGTTATCATATATTGTT

GCTCCTAATATTTCTGTGTTAGATAATTAGAGTAGCTTGGTTTGTAAGAATGTGATGTTGGTGG

GACTGTAGCAGAACAAGAAGGCCCTTATGGGTCAGTCATACCTCTCTT

SEQ ID NO: 27321 (3Ή arm)

In an embodiment, the replacement sequence comprises or consists of a Guanine (G) residue.

In an embodiment, to correct a mutation, e.g., an intronic 2789+5bp (G-^A) target site in the CFTR gene, the homology arms, e.g., the 5' and 3' homology arms, may each comprise about 1000 base pairs (bp) of sequence flanking the most distal gRNAs (e.g., 1200bp of sequence on either side of the mutation). The 5' homology arm is shown as bold sequence, the inserted base to correct the intronic 2789+5bp (G-^A) mutation is shown as lower case sequence, and the 3' homology arm is shown as no emphasis capitalized sequence.

TTTTTCTGTTTCATTCTGTGGTAAAGGTATCATTTGGCTAATTGTATAATTTCAGTGTCATTTC TAATATTCCAATTGTGATAGTATCAACACAAGATTAAATTTCTCTACATGGTTTATGAGAATGG AATGCCAAATTGAAATAGAACAGAGCACAGATGATCTAAATATAAAAAGAACTACAAAAATCAC AGTTGTTTAAAAAGGTTTTTTGTTTGTTTATATATGGTGCAGAACATTTGTTCCTTAGCCAAAT GTTTCCACCTTGAGAAAGCTATAGAGATTCTATGTAGTCCTAGTACCAATAATATGTTTTAACC TGAATGTACCTTATCTTTATTCATAAACTGTGACTTTTTACACTGCTGAAACTTTTTTTTTTAA GACAATCTCACTCTGTCGTCCAGTCTGGAGTGCAGCAGTGGTGTGATCTTGGCTCACTGCAACC TCTACCTTCTGTGTTCAAGCAATTCTGGTGCCTCGGCCACCTGAGTAGTTGGGATCACAGGTGT ACACCACCAGGCCTGGCTAATAGTTTTTGATATTTCTAGTAGAGATGAGTTTTGCCACATTGGC CAGGCTGGCCTGAAACTCCTGGCCTCAAGTGATCTGCCTGCCTTGGCCTCCCAAAGTGTTGGTA TTACAAGTGTGAGCCACTGTGCCTGGCCTGAAACTCATAATTCATTTCCATTAATATTAATCTC ACCTTTTCCAATAATTAATTGATTTCACAAGTATTAGTCCCCTATAATCATTGAATGGCTAATA AAATTATTTATAGCAAACAGATTAATTATCTGCCAGCAGTCTGAGATTAGTTTCTTTAAAAAAT GTTTATTATTTAAAACATTCAGCTGTGATCTTGGCTTTCTTGTGAGGTTCAATAGTTTCTATTG AGTAAAGGAGAGAAATGGCAGAGAATTTACTTCAGTGAAATTTGAATTCCATTAACTTAATGTG GTCTCATCACAAATAATAGTACTTAGAACACCTAGTACAGCTGCTGGACCCAGGAACACAAAGC AAAGGAAGATGAAATTGTGTGTACCTTGATATTGGTACACACATCAAATGGTGTGATGTGAATT TAGATGTGGGCATGGGAGGAATAGGTGAAGATGTTAGAAAAAAAATCAACTGTGTCTTGTTCCA TTCCAGGTGGCTGCTTCTTTGGTTGTGCTGTGGCTCCTTGGAAAGTGAgTATTCCATGTCCTAT TGTGTAGATTGTGTTTTATTTCTGTTGATTAAATATTGTAATCCACTATGTTTGTATGTATTGT AATCCACTTTGTTTCATTTCTCCCAAGCATTATGGTAGTGGAAAGATAAGGTTTTTTGTTTAAA TGATGACCATTAGTTGGGTGAGGTGACACATTCCTGTAGTCCTAGCTCCTCCACAGGCTGACGC AGGAGGATCACTTGAGCCCAGGAGTTCAGGGCTGTAGTGTTGTATCATTGTGAGTAGCCACCGC ACTCCAGCCTGGACAATATAGTGAGATCCTATATCTAAAATAAAATAAAATAAAATGAATAAAT TGTGAGCATGTGCAGCTCCTGCAGTTTCTAAAGAATATAGTTCTGTTCAGTTTCTGTGAAACAC AAT AAAAAT AT T T GAAAT AAC AT T AC AT AT TTAGGGTTTTCTT C AAAT T T T T T AAT T T AAT AAA GAACAACTCAATCTCTATCAATAGTGAGAAAACATATCTATTTTCTTGCAATAATAGTATGATT TTGAGGTTAAGGGTGCATGCTCTTCTAATGCAAAATATTGTATTTATTTAGACTCAAGTTTAGT TCCATTTACATGTATTGGAAATTCAGTAAGTAACTTTGGCTGCCAAATAACGATTTCCTATTTG CTTTACAGCACTCCTCTTCAAGACAAAGGGAATAGTACTCATAGTAGAAATAACAGCTATGCAG

TGATTATCACCAGCACCAGTTCGTATTATGTGTTTTACATTTACGTGGGAGTAGCCGACACTTT

GCTTGCTATGGGATTCTTCAGAGGTCTACCACTGGTGCATACTCTAATCACAGTGTCGAAAATT

TTACACCACAAAATGTTACATTCTGTTCTTCAAGCACCTATGTCAACCCTCAACACGTTGAAAG

CAGGTACTTTACTAGGTCTAAGAAATGAAACTGCTGATCCACCATCAATAGGGCCTGTGGTTTT

GTTGGTTTTCTAATGGCAGTGCTGGCTTTTGCACAGAGGCATGTGCCCTTTGTTGAACCTCCAT

TTGACTGGCATGCACATGTCTCAGATATTATAGGTTATCATATATTGTTGCTCCTAATATTTCT

GTGTTAGATAATTAGAGTAGCTTGGTTTGTAAGAATGTGATGTTGGTGGGACTGTAGCAGAACA

AGAAGGCCCTTATGGGTCAGTCATACCTCTCTT

(Template Construct 42; SEQ ID NO: 27322)

As described below in Table 49, shorter homology arms, e.g., 5' and/or 3' homology arms may be used.

It is contemplated herein that one or both homology arms may be shortened to avoid including certain sequence repeat elements, e.g., Alu repeats, LINE elements. For example, a 5' homology arm may be shortened to avoid a sequence repeat element. In other embodiments, a 3' homology arm may be shortened to avoid a sequence repeat element. In some embodiments, both the 5' and the 3' homology arms may be shortened to avoid including certain sequence repeat elements.

In an embodiment, to correct an intronic 2789+5bp (G-^A) mutation in the CFTR gene, the 5' homology arm may be shortened less than 1000 nucleotides, e.g., e.g., 500 nucleotides, to avoid inclusion of a LINE repeat element in the 5' homology arm. The 5' homology arm is shown as bold sequence, the inserted base to correct the intronic 2789+5bp (G-^A) mutation is shown as lower case sequence, and the 3' homology arm is shown as no emphasis capitalized sequence.

TCTCACCTTTTCCAATAATTAATTGATTTCACAAGTATTAGTCCCCTATAATCATTGAATGGCT AATAAAATTATTTATAGCAAACAGATTAATTATCTGCCAGCAGTCTGAGATTAGTTTCTTTAAA AAATGTTTATTATTTAAAACATTCAGCTGTGATCTTGGCTTTCTTGTGAGGTTCAATAGTTTCT ATTGAGTAAAGGAGAGAAATGGCAGAGAATTTACTTCAGTGAAATTTGAATTCCATTAACTTAA TGTGGTCTCATCACAAATAATAGTACTTAGAACACCTAGTACAGCTGCTGGACCCAGGAACACA AAGCAAAGGAAGATGAAATTGTGTGTACCTTGATATTGGTACACACATCAAATGGTGTGATGTG AATTTAGATGTGGGCATGGGAGGAATAGGTGAAGATGTTAGAAAAAAAATCAACTGTGTCTTGT TCCATTCCAGGTGGCTGCTTCTTTGGTTGTGCTGTGGCTCCTTGGAAAGTGAgTAT TCCATGTC

CTATTGTGTAGATTGTGTTTTATTTCTGTTGATTAAATATTGTAATCCACTATGTTTGTATGTA

TTGTAATCCACTTTGTTTCATTTCTCCCAAGCATTATGGTAGTGGAAAGATAAGGTTTTTTGTT

TAAATGATGACCATTAGTTGGGTGAGGTGACACATTCCTGTAGTCCTAGCTCCTCCACAGGCTG

ACGCAGGAGGATCACTTGAGCCCAGGAGTTCAGGGCTGTAGTGTTGTATCATTGTGAGTAGCCA

CCGCACTCCAGCCTGGACAATATAGTGAGATCCTATATCTAAAATAAAATAAAATAAAATGAAT

AAATTGTGAGCATGTGCAGCTCCTGCAGTTTCTAAAGAATATAGTTCTGTTCAGTTTCTGTGAA

ACACAATAAAAATATTTGAAATAACATTACATATTTAGGGTTTTCTTCAAATTTTTTAATTTAA

TAAAGAACAACTCAATCTCTATCAATAGTGAGAAAACATAT

(Template Construct 43; SEQ ID NO: 27323)

It is contemplated herein that template nucleic acids for correcting a mutation may designed for use as a single- stranded oligonucleotide (ssODN). When using a ssODN, 5' and 3' homology arms may range up to about 200 base pairs (bp) in length, e.g., at least 25, 50, 75, 100, 125, 150, 175, or 200 bp in length. Longer homology arms are also contemplated for ssODNs as improvements in oligonucleotide synthesis continue to be made.

In an embodiment, an ssODN may be used to correct a mutation, e.g., an intronic

2789+5bp (G-^A) target site in the CFTR gene. For example, the ssODN may include 5' and 3' homology arms as shown below. The 5' homology arm is shown as bold sequence, the inserted bases to correct the intronic 2789+5bp (G-^A) mutation is shown as lower case sequence, and the 3' homology arm is shown as no emphasis capitalized sequence.

AAAAAAAATCAACTGTGTCTTGTTCCATTCCAGGTGGCTGCTTCTTTGGTTGTGCTGTGGCTCC

TTGGAAAGTGAgTATTCCATGTCCTATTGTGTAGATTGTGTTTTATTTCTGTTGATTAAATATT

GTAATCCACTATGTTTGTATGTA

(Template Construct 44; SEQ ID NO: 27324)

In an embodiment, to correct a mutation, e.g., an intronic 2789+5bp (G-^A) target site in the CFTR gene, and concomitantly introduce a silent sense mutation to disrupt subsequent Cas9 binding and cleavage, the homology arms, e.g., the 5' and 3' homology arms, may each comprise about 1000 base pairs (bp) of sequence flanking the most distal gRNAs (e.g., 1200bp of sequence on either side of the mutation). The 5' homology arm is shown as bold sequence, the inserted base to correct the intronic 2789+5bp (G-^A) mutation is shown as lower case sequence, the silent sense mutation is shown as lower case underlined and italicized sequence, and the 3' homology arm is shown as no emphasis capitalized sequence.

TTTTTCTGTTTCATTCTGTGGTAAAGGTATCATTTGGCTAATTGTATAATTTCAGTGTCATTTC TAATATTCCAATTGTGATAGTATCAACACAAGATTAAATTTCTCTACATGGTTTATGAGAATGG AATGCCAAATTGAAATAGAACAGAGCACAGATGATCTAAATATAAAAAGAACTACAAAAATCAC AGTTGTTTAAAAAGGTTTTTTGTTTGTTTATATATGGTGCAGAACATTTGTTCCTTAGCCAAAT GTTTCCACCTTGAGAAAGCTATAGAGATTCTATGTAGTCCTAGTACCAATAATATGTTTTAACC TGAATGTACCTTATCTTTATTCATAAACTGTGACTTTTTACACTGCTGAAACTTTTTTTTTTAA GACAATCTCACTCTGTCGTCCAGTCTGGAGTGCAGCAGTGGTGTGATCTTGGCTCACTGCAACC TCTACCTTCTGTGTTCAAGCAATTCTGGTGCCTCGGCCACCTGAGTAGTTGGGATCACAGGTGT ACACCACCAGGCCTGGCTAATAGTTTTTGATATTTCTAGTAGAGATGAGTTTTGCCACATTGGC CAGGCTGGCCTGAAACTCCTGGCCTCAAGTGATCTGCCTGCCTTGGCCTCCCAAAGTGTTGGTA TTACAAGTGTGAGCCACTGTGCCTGGCCTGAAACTCATAATTCATTTCCATTAATATTAATCTC ACCTTTTCCAATAATTAATTGATTTCACAAGTATTAGTCCCCTATAATCATTGAATGGCTAATA AAATTATTTATAGCAAACAGATTAATTATCTGCCAGCAGTCTGAGATTAGTTTCTTTAAAAAAT GTTTATTATTTAAAACATTCAGCTGTGATCTTGGCTTTCTTGTGAGGTTCAATAGTTTCTATTG AGTAAAGGAGAGAAATGGCAGAGAATTTACTTCAGTGAAATTTGAATTCCATTAACTTAATGTG GTCTCATCACAAATAATAGTACTTAGAACACCTAGTACAGCTGCTGGACCCAGGAACACAAAGC AAAGGAAGATGAAATTGTGTGTACCTTGATATTGGTACACACATCAAATGGTGTGATGTGAATT TAGATGTGGGCATGGGAGGAATAGGTGAAGATGTTAGAAAAAAAATCAACTGTGTCTTGTTCCA TTCCAGGTGGCTGCTTCTTTGGTTGTGCTGTGGCTCCTTGGAAAGTGAgTATTggATGTCCTAT TGTGTAGATTGTGTTTTATTTCTGTTGATTAAATATTGTAATCCACTATGTTTGTATGTATTGT AATCCACTTTGTTTCATTTCTCCCAAGCATTATGGTAGTGGAAAGATAAGGTTTTTTGTTTAAA TGATGACCATTAGTTGGGTGAGGTGACACATTCCTGTAGTCCTAGCTCCTCCACAGGCTGACGC AGGAGGATCACTTGAGCCCAGGAGTTCAGGGCTGTAGTGTTGTATCATTGTGAGTAGCCACCGC ACTCCAGCCTGGACAATATAGTGAGATCCTATATCTAAAATAAAATAAAATAAAATGAATAAAT TGTGAGCATGTGCAGCTCCTGCAGTTTCTAAAGAATATAGTTCTGTTCAGTTTCTGTGAAACAC AAT AAAAAT AT T T GAAAT AAC AT T AC AT AT TTAGGGTTTTCTT C AAAT T T T T T AAT T T AAT AAA GAACAACTCAATCTCTATCAATAGTGAGAAAACATATCTATTTTCTTGCAATAATAGTATGATT TTGAGGTTAAGGGTGCATGCTCTTCTAATGCAAAATATTGTATTTATTTAGACTCAAGTTTAGT TCCATTTACATGTATTGGAAATTCAGTAAGTAACTTTGGCTGCCAAATAACGATTTCCTATTTG CTTTACAGCACTCCTCTTCAAGACAAAGGGAATAGTACTCATAGTAGAAATAACAGCTATGCAG TGATTATCACCAGCACCAGTTCGTATTATGTGTTTTACATTTACGTGGGAGTAGCCGACACTTT

GCTTGCTATGGGATTCTTCAGAGGTCTACCACTGGTGCATACTCTAATCACAGTGTCGAAAATT

TTACACCACAAAATGTTACATTCTGTTCTTCAAGCACCTATGTCAACCCTCAACACGTTGAAAG

CAGGTACTTTACTAGGTCTAAGAAATGAAACTGCTGATCCACCATCAATAGGGCCTGTGGTTTT

GTTGGTTTTCTAATGGCAGTGCTGGCTTTTGCACAGAGGCATGTGCCCTTTGTTGAACCTCCAT

TTGACTGGCATGCACATGTCTCAGATATTATAGGTTATCATATATTGTTGCTCCTAATATTTCT

GTGTTAGATAATTAGAGTAGCTTGGTTTGTAAGAATGTGATGTTGGTGGGACTGTAGCAGAACA

AGAAGGCCCTTATGGGTCAGTCATACCTCTCTT

(Template Construct 45; SEQ ID NO: 27325)

In an embodiment, to correct a mutation, e.g., an intronic 2789+5bp (G-^A) target site in the CFTR gene, and concomitantly introduce a silent mutation to disrupt subsequent Cas9 binding and cleavage, the 5' homology arm may be shortened less than 750 nucleotides, e.g., 500 nucleotides, to avoid inclusion of a LINE repeat element in the 5' homology arm. The 5' homology arm is shown as bold sequence, the inserted base to correct the intronic 2789+5bp (G-^A) mutation is shown as lower case sequence, the silent sense mutation is shown as lower case underlined and italicized sequence, and the 3' homology arm is shown as no emphasis capitalized sequence.

TCTCACCTTTTCCAATAATTAATTGATTTCACAAGTATTAGTCCCCTATAATCATTGAATGGCT AATAAAATTATTTATAGCAAACAGATTAATTATCTGCCAGCAGTCTGAGATTAGTTTCTTTAAA AAATGTTTATTATTTAAAACATTCAGCTGTGATCTTGGCTTTCTTGTGAGGTTCAATAGTTTCT ATTGAGTAAAGGAGAGAAATGGCAGAGAATTTACTTCAGTGAAATTTGAATTCCATTAACTTAA TGTGGTCTCATCACAAATAATAGTACTTAGAACACCTAGTACAGCTGCTGGACCCAGGAACACA AAGCAAAGGAAGATGAAATTGTGTGTACCTTGATATTGGTACACACATCAAATGGTGTGATGTG AATTTAGATGTGGGCATGGGAGGAATAGGTGAAGATGTTAGAAAAAAAATCAACTGTGTCTTGT TCCATTCCAGGTGGCTGCTTCTTTGGTTGTGCTGTGGCTCCTTGGAAAGTGAgTATTggATGTC CTATTGTGTAGATTGTGTTTTATTTCTGTTGATTAAATATTGTAATCCACTATGTTTGTATGTA TTGTAATCCACTTTGTTTCATTTCTCCCAAGCATTATGGTAGTGGAAAGATAAGGTTTTTTGTT TAAATGATGACCATTAGTTGGGTGAGGTGACACATTCCTGTAGTCCTAGCTCCTCCACAGGCTG ACGCAGGAGGATCACTTGAGCCCAGGAGTTCAGGGCTGTAGTGTTGTATCATTGTGAGTAGCCA CCGCACTCCAGCCTGGACAATATAGTGAGATCCTATATCTAAAATAAAATAAAATAAAATGAAT AAATTGTGAGCATGTGCAGCTCCTGCAGTTTCTAAAGAATATAGTTCTGTTCAGTTTCTGTGAA AC AC AAT AAAAAT AT T T GAAAT AAC AT T AC AT AT TTAGGGTTTTCTT C AAAT T T T T T AAT T T AA T AAAG AAC AAC TCAATCTCTATCAATAGT G AG AAAAC AT AT

(Template Construct 46; SEQ ID NO: 27326)

In an embodiment, an ssODN may be to correct a mutation, e.g., an intronic 2789+5bp (G-^A) target site in the CFTR gene, and concomitantly introduce a silent mutation to disrupt subsequent Cas9 binding and cleavage. For example, the ssODN may include 5' and 3' homology arms as shown below. The 5' homology arm is shown as bold sequence, the inserted base to correct the intronic 2789+5bp (G-^A) mutation is shown as lower case sequence, the silent sense mutation is shown as lower case underlined and italicized sequence, and the 3' homology arm is shown as no emphasis capitalized sequence.

AAAAAAAATCAACTGTGTCTTGTTCCATTCCAGGTGGCTGCTTCTTTGGTTGTGCTGTGGCTCC

TTGGAAAGTGAgTATTggATGTCCTATTGTGTAGATTGTGTTTTATTTCTGTTGATTAAATATT

GTAATCCACTATGTTTGTATGTA

(Template Construct 47; SEQ ID NO: 27327)

The underlined G has been changed from a C to G at that position, so that wild-type CFTR is still transcribed, but the PAM sequence CCA has been modified to reduce or eliminate Cas9 cleavage at that locus.

Exemplary template nucleic acids (also referred to herein as donor constructs) to correction a mutation, e.g., an intronic 3272-26bp (A- G) target site in the CFTR gene, are provided.

Suitable sequence for the 5' homology arm can be selected from (e.g., includes a portion of) or include the following sequence:

GTGCACATGTACCCTAAAACTTAAAGTATAATAAAAAAAATAAAAAAAAGTTTGAGGTGTTTAA AG TAT GC AAAAAAAAAAAAAG AAAT AAAT C AC T G AC AC AC TTTGTCCACTTTGCAATGT G AAAA TGTTTACTCACCAACATGTTTTCTTTGATCTTACAGTTGTTATTAATTGTGATTGGAGCTATAG CAGTTGTCGCAGTTTTACAACCCTACATCTTTGTTGCAACAGTGCCAGTGATAGTGGCTTTTAT TATGTTGAGAGCATATTTCCTCCAAACCTCACAGCAACTCAAACAACTGGAATCTGAAGGTATG ACAGTGAATGTGCGATACTCATCTTGTAAAAAAGCTATAAGAGCTATTTGAGATTCTTTATTGT TAATCTACTTAAAAAAAATTCTGCTTTTAAACTTTTACATCATATAACAATAATTTTTTTCTAC ATGCATGTGTATATAAAAGGAAACTATATTACAAAGTACACATGGATTTTTTTTCTTAATTAAT GACCATGTGACTTCATTTTGGTTTTAAAATAGGTATATAGAATCTTACCACAGTTGGTGTACAG GACATTCATTTATAATAAACTTATATCAGTCAAATTAAACAAGGATAGTGCTGCTATTACTAAA

GGTTTCTCTGGGTTCCCAAATGATACTTGACCAAATTTGTCCCTTTGGCTTGTTGTCTTCAGAC

ACCCTTTCTTCATGTGTTGGAGCTGCCATTTCGTGTGCCCCCAAACTCTACTTGAGCTGTTAGG

GAATCACATTTTGCAGTGACAGCCTTAGTGTGGGTGCATTTTCAGGCAATACTTTTTCAGTATA

TTTCTGCTTTGTAGATTATTAGCTAAATCAAGTCACATAAACTTCCTTAATTTAGATACTTGAA

AAAATTGTCTTAAAAGAAAATTTTTTTAGTAAGAATTAATTTAGAATTAGCCAGAAAACTCCCA

GTGGTAGCCAAGAAAGAGGAATAAATATTGGTGGTAATTTTTTAAGTTCCCATCTCTGGTAGCC

AAGTAAAAAAAGAGGGTAACTCATTAATAAAATAACAAATCATATCTATTCAAAGAATGGCACC

AGTGTGAAAAAAAGCTTTTTAACCAATGACATTTGTGATATGATTATTCTAATTTAGTCTTTTT

CAGGTACAAGATATTATGAAATTACATTTTGTGTTTATGTTATTTGCA

SEQ ID NO: 27328 (5Ή arm)

Suitable sequence for the 3' homology arm can be selected from (e.g., includes a portion of) or include the following sequence:

TGTTTTCTATGGAAATATTTCACAGGCAGGAGTCCAATTTTCACTCATCTTGTTACAAGCTTAA AAGGACTATGGACACTTCGTGCCTTCGGACGGCAGCCTTACTTTGAAACTCTGTTCCACAAAGC TCTGAATTTACATACTGCCAACTGGTTCTTGTACCTGTCAACACTGCGCTGGTTCCAAATGAGA ATAGAAATGATTTTTGTCATCTTCTTCATTGCTGTTACCTTCATTTCCATTTTAACAACAGGTA CTATGAACTCATTAACTTTAGCTAAGCATTTAAGTAAAAAATTTTCAATGAATAAAATGCTGCA TTCTATAGGTTATCAATTTTTGATATCTTTAGAGTTTAGTAATTAACAAATTTGTTGGTTTATT ATTGAACAAGTGATTTCTTTGAATTTCCATTGTTTTATTGTTAAACAAATAATTTCCTTGAAAT CGGAT AT AT AT AT AT AT ATGT AT AT AT AT AT AT AT AT AT AT AT AT AT AT ACAT AT AT AT AT AT A GTATTATCCCTGTTTTCACAGTTTTAAAAACCGATGCACACAGATTGTCAGATAGCAATTCTGT GATTGAAGGGGAAATATGTCACCTCTTCATACTCATATTGGTGAAGGGTCCTAGCTTCAAAATT AATAGATTCCTAAAGAGGGGAAATGAAACATCCGCATTTACACACACACACACACACACACACA CAGAGTTCCTCTTGTCGGTAAGTTTTGTTTTTTTTAAATCTCTACTAGATAAAATTTGTTATCT AATTGTGAGTTTTACACAAAGAAAAACTGTCACAGAAAAGAAAGACAGTGTCACATTTTTCAAA AGAAAAAGAAGAAAAGAAAGTGCCATGTTTTTCAAATACAAATGTTCTGGATTGATTTTAGGAT CTTTAGTGAAAAACAAAGTATTTCATAATAAGTAAAATAAAAATCTATGTAGGTAAATTTGTTT CTCTAATTTAAGAATTTGAATTTCTGAGTATTTATGATAAGTGTTGAAATAACTTCTTATATGT GACAGTGAATACTGGCAGAGCAAATGCCAAATCAATGCCAAATCTGTAGGATCATTTGATTGTA GGAACAGAATTCTACTCAAACCGAAAGCAGGCATTTGCTGGAGTTACAGAAAGGCCTCATGGAA CACCGAGAAGGTGGTGCCATTCGACTCTTAAAGAAGCTGCAACAGGCA SEQ ID NO: 27329 (3Ή arm)

In an embodiment, the replacement sequence comprises or consists of an Adenine (A) residue.

In an embodiment, to correct a mutation, e.g., an intronic 3272-26bp (A- G) target site in the CFTR gene, the homology arms, e.g., the 5' and 3' homology arms, may each comprise about 1000 base pairs (bp) of sequence flanking the most distal gRNAs (e.g., 1200bp of sequence on either side of the mutation). The 5' homology arm is shown as bold sequence, the inserted base to correct the intronic 3272-26bp (A- G) mutation is shown as lower case sequence, and the 3' homology arm is shown as no emphasis capitalized sequence.

GTGCACATGTACCCTAAAACTTAAAGTATAATAAAAAAAATAAAAAAAAGTTTGAGGTGTTTAA AGTATGCAAAAAAAAAAAAAGAAATAAATCACTGACACACTTTGTCCACTTTGCAATGTGAAAA TGTTTACTCACCAACATGTTTTCTTTGATCTTACAGTTGTTATTAATTGTGATTGGAGCTATAG CAGTTGTCGCAGTTTTACAACCCTACATCTTTGTTGCAACAGTGCCAGTGATAGTGGCTTTTAT TATGTTGAGAGCATATTTCCTCCAAACCTCACAGCAACTCAAACAACTGGAATCTGAAGGTATG ACAGTGAATGTGCGATACTCATCTTGTAAAAAAGCTATAAGAGCTATTTGAGATTCTTTATTGT TAATCTACTTAAAAAAAATTCTGCTTTTAAACTTTTACATCATATAACAATAATTTTTTTCTAC ATGCATGTGTATATAAAAGGAAACTATATTACAAAGTACACATGGATTTTTTTTCTTAATTAAT GACCATGTGACTTCATTTTGGTTTTAAAATAGGTATATAGAATCTTACCACAGTTGGTGTACAG GACATTCATTTATAATAAACTTATATCAGTCAAATTAAACAAGGATAGTGCTGCTATTACTAAA GGTTTCTCTGGGTTCCCAAATGATACTTGACCAAATTTGTCCCTTTGGCTTGTTGTCTTCAGAC ACCCTTTCTTCATGTGTTGGAGCTGCCATTTCGTGTGCCCCCAAACTCTACTTGAGCTGTTAGG GAATCACATTTTGCAGTGACAGCCTTAGTGTGGGTGCATTTTCAGGCAATACTTTTTCAGTATA TTTCTGCTTTGTAGATTATTAGCTAAATCAAGTCACATAAACTTCCTTAATTTAGATACTTGAA AAAATTGTCTTAAAAGAAAATTTTTTTAGTAAGAATTAATTTAGAATTAGCCAGAAAACTCCCA GTGGTAGCCAAGAAAGAGGAATAAATATTGGTGGTAATTTTTTAAGTTCCCATCTCTGGTAGCC AAGTAAAAAAAGAGGGTAACTCATTAATAAAATAACAAATCATATCTATTCAAAGAATGGCACC AGTGTGAAAAAAAGCTTTTTAACCAATGACATTTGTGATATGATTATTCTAATTTAGTCTTTTT CAGGTACAAGATATTATGAAATTACATTTTGTGTTTATGTTATTTGCAa T G T T T T C T ATGG AAA TAT T TCACAGGCAGGAGTCCAAT T T TCACTCATCT TGT TACAAGCT TAAAAGGACTATGGACAC T TCGTGCCT TCGGACGGCAGCCT TACT T TGAAACTCTGT TCCACAAAGCTCTGAAT T TACATAC TGCCAACTGGT TCT TGTACCTGTCAACACTGCGCTGGT TCCAAATGAGAATAGAAATGAT T T T T GTCATCTTCTTCATTGCTGTTACCTTCATTTCCATTTTAACAACAGGTACTATGAACTCATTAA

CTTTAGCTAAGCATTTAAGTAAAAAATTTTCAATGAATAAAATGCTGCATTCTATAGGTTATCA

ATTTTTGATATCTTTAGAGTTTAGTAATTAACAAATTTGTTGGTTTATTATTGAACAAGTGATT

TCTTTGAATTTCCATTGTTTTATTGTTAAACAAATAATTTCCTTGAAATCGGATATATATATAT

ATATGTATATATATATATATATATATATATATATACATATATATATATAGTATTATCCCTGTTT

TCACAGTTTTAAAAACCGATGCACACAGATTGTCAGATAGCAATTCTGTGATTGAAGGGGAAAT

ATGTCACCTCTTCATACTCATATTGGTGAAGGGTCCTAGCTTCAAAATTAATAGATTCCTAAAG

AGGGGAAATGAAACATCCGCATTTACACACACACACACACACACACACACAGAGTTCCTCTTGT

CGGTAAGTTTTGTTTTTTTTAAATCTCTACTAGATAAAATTTGTTATCTAATTGTGAGTTTTAC

AC AAAG AAAAAC T G T C AC AG AAAAG AAAG AC AG TGTCACATTTTT C AAAAG AAAAAG AAG AAAA

GAAAGTGCCATGTTTTTCAAATACAAATGTTCTGGATTGATTTTAGGATCTTTAGTGAAAAACA

AAGTATTTCATAATAAGTAAAATAAAAATCTATGTAGGTAAATTTGTTTCTCTAATTTAAGAAT

TTGAATTTCTGAGTATTTATGATAAGTGTTGAAATAACTTCTTATATGTGACAGTGAATACTGG

CAGAGCAAATGCCAAATCAATGCCAAATCTGTAGGATCATTTGATTGTAGGAACAGAATTCTAC

TCAAACCGAAAGCAGGCATTTGCTGGAGTTACAGAAAGGCCTCATGGAACACCGAGAAGGTGGT

GCCATTCGACTCTTAAAGAAGCTGCAACAGGCA

(Template Construct 48; SEQ ID NO: 27330)

As described below in Table 49, shorter homology arms, e.g., 5' and/or 3' homology arms may be used.

It is contemplated herein that one or both homology arms may be shortened to avoid including certain sequence repeat elements, e.g., Alu repeats, LINE elements. For example, a 5' homology arm may be shortened to avoid a sequence repeat element. In other embodiments, a 3' homology arm may be shortened to avoid a sequence repeat element. In some embodiments, both the 5' and the 3' homology arms may be shortened to avoid including certain sequence repeat elements.

In an embodiment, to correct an intronic 3272-26bp (A- G) mutation in the CFTR gene, the 5' homology arm may be shortened less than 1000 nucleotides, e.g., e.g., 500 nucleotides, to avoid inclusion of a LINE repeat element in the 5' homology arm. The 5' homology arm is shown as bold sequence, the inserted base to correct the intronic 3272-26bp (A- G) mutation is shown as lower case sequence, and the 3' homology arm is shown as no emphasis capitalized sequence. AGACACCCTTTCTTCATGTGTTGGAGCTGCCATTTCGTGTGCCCCCAAACTCTACTTGAGCTGT

TAGGGAATCACATTTTGCAGTGACAGCCTTAGTGTGGGTGCATTTTCAGGCAATACTTTTTCAG

TATATTTCTGCTTTGTAGATTATTAGCTAAATCAAGTCACATAAACTTCCTTAATTTAGATACT

TGAAAAAATTGTCTTAAAAGAAAATTTTTTTAGTAAGAATTAATTTAGAATTAGCCAGAAAACT

CCCAGTGGTAGCCAAGAAAGAGGAATAAATATTGGTGGTAATTTTTTAAGTTCCCATCTCTGGT

AGCCAAGTAAAAAAAGAGGGTAACTCATTAATAAAATAACAAATCATATCTATTCAAAGAATGG

CACCAGTGTGAAAAAAAGCTTTTTAACCAATGACATTTGTGATATGATTATTCTAATTTAGTCT

TTTTCAGGTACAAGATATTATGAAATTACATTTTGTGTTTATGTTATTTGCAa T G T T T T CTATG

GAAATATTTCACAGGCAGGAGTCCAATTTTCACTCATCTTGTTACAAGCTTAAAAGGACTATGG

ACACTTCGTGCCTTCGGACGGCAGCCTTACTTTGAAACTCTGTTCCACAAAGCTCTGAATTTAC

ATACTGCCAACTGGTTCTTGTACCTGTCAACACTGCGCTGGTTCCAAATGAGAATAGAAATGAT

TTTTGTCATCTTCTTCATTGCTGTTACCTTCATTTCCATTTTAACAACAGGTACTATGAACTCA

TTAACTTTAGCTAAGCATTTAAGTAAAAAATTTTCAATGAATAAAATGCTGCATTCTATAGGTT

ATCAATTTTTGATATCTTTAGAGTTTAGTAATTAACAAATTTGTTGGTTTATTATTGAACAAGT

GATTTCTTTGAATTTCCATTGTTTTATTGTTAAACAAATAATTTCCTTGAAATCGGATATATAT

AT AT AT ATGT AT AT AT AT AT AT AT AT AT AT AT AT AT AT ACA

(Template Construct 49; SEQ ID NO: 27331)

It is contemplated herein that template nucleic acids for correcting a mutation may designed for use as a single- stranded oligonucleotide (ssODN). When using a ssODN, 5' and 3' homology arms may range up to about 200 base pairs (bp) in length, e.g., at least 25, 50, 75, 100, 125, 150, 175, or 200 bp in length. Longer homology arms are also contemplated for ssODNs as improvements in oligonucleotide synthesis continue to be made.

In an embodiment, an ssODN may be used to correct a mutation, e.g., an intronic 3272- 26bp (A- G) target site in the CFTR gene. For example, the ssODN may include 5' and 3' homology arms as shown below. The 5' homology arm is shown as bold sequence, the inserted bases to correct the intronic 3272-26bp (A- G) mutation is shown as lower case sequence, and the 3' homology arm is shown as no emphasis capitalized sequence.

ATATGATTATTCTAATTTAGTCTTTTTCAGGTACAAGATATTATGAAATTACATTTTGTGTTTA

TGTTATTTGCAaTGTTTTCTATGGAAATATTTCACAGGCAGGAGTCCAATTTTCACTCATCTTG T T AC AAG C T T AAAAG GACTATGG

(Template Construct 50; SEQ ID NO: 27332) In an embodiment, to correct a mutation, e.g., an intronic 3272-26bp (A- G) target site in the CFTR gene, and concomitantly introduce a silent sense mutation to disrupt subsequent Cas9 binding and cleavage, the homology arms, e.g., the 5' and 3' homology arms, may each comprise about 1000 base pairs (bp) of sequence flanking the most distal gRNAs (e.g., 1200bp of sequence on either side of the mutation). The 5' homology arm is shown as bold sequence, the inserted base to correct the intronic 3272-26bp (A- G) mutation is shown as lower case sequence, the silent sense mutation is shown as lower case underlined and italicized sequence, and the 3' homology arm is shown as no emphasis capitalized sequence.

GTGCACATGTACCCTAAAACTTAAAGTATAATAAAAAAAATAAAAAAAAGTTTGAGGTGTTTAA AGTATGCAAAAAAAAAAAAAGAAATAAATCACTGACACACTTTGTCCACTTTGCAATGTGAAAA TGTTTACTCACCAACATGTTTTCTTTGATCTTACAGTTGTTATTAATTGTGATTGGAGCTATAG CAGTTGTCGCAGTTTTACAACCCTACATCTTTGTTGCAACAGTGCCAGTGATAGTGGCTTTTAT TATGTTGAGAGCATATTTCCTCCAAACCTCACAGCAACTCAAACAACTGGAATCTGAAGGTATG ACAGTGAATGTGCGATACTCATCTTGTAAAAAAGCTATAAGAGCTATTTGAGATTCTTTATTGT TAATCTACTTAAAAAAAATTCTGCTTTTAAACTTTTACATCATATAACAATAATTTTTTTCTAC ATGCATGTGTATATAAAAGGAAACTATATTACAAAGTACACATGGATTTTTTTTCTTAATTAAT GACCATGTGACTTCATTTTGGTTTTAAAATAGGTATATAGAATCTTACCACAGTTGGTGTACAG GACATTCATTTATAATAAACTTATATCAGTCAAATTAAACAAGGATAGTGCTGCTATTACTAAA GGTTTCTCTGGGTTCCCAAATGATACTTGACCAAATTTGTCCCTTTGGCTTGTTGTCTTCAGAC ACCCTTTCTTCATGTGTTGGAGCTGCCATTTCGTGTGCCCCCAAACTCTACTTGAGCTGTTAGG GAATCACATTTTGCAGTGACAGCCTTAGTGTGGGTGCATTTTCAGGCAATACTTTTTCAGTATA TTTCTGCTTTGTAGATTATTAGCTAAATCAAGTCACATAAACTTCCTTAATTTAGATACTTGAA AAAATTGTCTTAAAAGAAAATTTTTTTAGTAAGAATTAATTTAGAATTAGCCAGAAAACTCCCA GTGGTAGCCAAGAAAGAGGAATAAATATTGGTGGTAATTTTTTAAGTTCCCATCTCTGGTAGCC AAGTAAAAAAAGAGGGTAACTCATTAATAAAATAACAAATCATATCTATTCAAAGAATGGCACC AGTGTGAAAAAAAGCTTTTTAACCAATGACATTTGTGATATGATTATTCTAATTTAGTCTTTTT CAGGTACAAGATATTATGAAATTACATTTTGTGTTTATGTTATTTGCAaTGTTTTCTATccAAA TATTTCACAGGCAGGAGTCCAATTTTCACTCATCTTGTTACAAGCTTAAAAGGACTATGGACAC TTCGTGCCTTCGGACGGCAGCCTTACTTTGAAACTCTGTTCCACAAAGCTCTGAATTTACATAC TGCCAACTGGTTCTTGTACCTGTCAACACTGCGCTGGTTCCAAATGAGAATAGAAATGATTTTT GTCATCTTCTTCATTGCTGTTACCTTCATTTCCATTTTAACAACAGGTACTATGAACTCATTAA CTTTAGCTAAGCATTTAAGTAAAAAATTTTCAATGAATAAAATGCTGCATTCTATAGGTTATCA

ATTTTTGATATCTTTAGAGTTTAGTAATTAACAAATTTGTTGGTTTATTATTGAACAAGTGATT

TCTTTGAATTTCCATTGTTTTATTGTTAAACAAATAATTTCCTTGAAATCGGATATATATATAT

ATATGTATATATATATATATATATATATATATATACATATATATATATAGTATTATCCCTGTTT

TCACAGTTTTAAAAACCGATGCACACAGATTGTCAGATAGCAATTCTGTGATTGAAGGGGAAAT

ATGTCACCTCTTCATACTCATATTGGTGAAGGGTCCTAGCTTCAAAATTAATAGATTCCTAAAG

AGGGGAAATGAAACATCCGCATTTACACACACACACACACACACACACACAGAGTTCCTCTTGT

CGGTAAGTTTTGTTTTTTTTAAATCTCTACTAGATAAAATTTGTTATCTAATTGTGAGTTTTAC

AC AAAG AAAAAC T G T C AC AG AAAAG AAAG AC AG TGTCACATTTTT C AAAAG AAAAAG AAG AAAA

GAAAGTGCCATGTTTTTCAAATACAAATGTTCTGGATTGATTTTAGGATCTTTAGTGAAAAACA

AAGTATTTCATAATAAGTAAAATAAAAATCTATGTAGGTAAATTTGTTTCTCTAATTTAAGAAT

TTGAATTTCTGAGTATTTATGATAAGTGTTGAAATAACTTCTTATATGTGACAGTGAATACTGG

CAGAGCAAATGCCAAATCAATGCCAAATCTGTAGGATCATTTGATTGTAGGAACAGAATTCTAC

TCAAACCGAAAGCAGGCATTTGCTGGAGTTACAGAAAGGCCTCATGGAACACCGAGAAGGTGGT

GCCATTCGACTCTTAAAGAAGCTGCAACAGGCA

(Template Construct 51; SEQ ID NO: 27333)

In an embodiment, to correct a mutation, e.g., an intronic 3272-26bp (A- G) target site in the CFTR gene, and concomitantly introduce a silent mutation to disrupt subsequent Cas9 binding and cleavage, the 5' homology arm may be shortened less than 750 nucleotides, e.g., 500 nucleotides, to avoid inclusion of a LINE repeat element in the 5' homology arm. The 5' homology arm is shown as bold sequence, the inserted base to correct the intronic 3272-26bp (A- G) mutation is shown as lower case sequence, the silent sense mutation is shown as lower case underlined and italicized sequence, and the 3' homology arm is shown as no emphasis capitalized sequence.

AGACACCCTTTCTTCATGTGTTGGAGCTGCCATTTCGTGTGCCCCCAAACTCTACTTGAGCTGT TAGGGAATCACATTTTGCAGTGACAGCCTTAGTGTGGGTGCATTTTCAGGCAATACTTTTTCAG TATATTTCTGCTTTGTAGATTATTAGCTAAATCAAGTCACATAAACTTCCTTAATTTAGATACT TGAAAAAATTGTCTTAAAAGAAAATTTTTTTAGTAAGAATTAATTTAGAATTAGCCAGAAAACT CCCAGTGGTAGCCAAGAAAGAGGAATAAATATTGGTGGTAATTTTTTAAGTTCCCATCTCTGGT AGCCAAGTAAAAAAAGAGGGTAACTCATTAATAAAATAACAAATCATATCTATTCAAAGAATGG CACCAGTGTGAAAAAAAGCTTTTTAACCAATGACATTTGTGATATGATTATTCTAATTTAGTCT TTTTCAGGTACAAGATATTATGAAATTACATTTTGTGTTTATGTTATTTGCAa TGTTTTCTATc cAAATATTTCACAGGCAGGAGTCCAATTTTCACTCATCTTGTTACAAGCTTAAAAGGACTATGG

ACACTTCGTGCCTTCGGACGGCAGCCTTACTTTGAAACTCTGTTCCACAAAGCTCTGAATTTAC

ATACTGCCAACTGGTTCTTGTACCTGTCAACACTGCGCTGGTTCCAAATGAGAATAGAAATGAT

TTTTGTCATCTTCTTCATTGCTGTTACCTTCATTTCCATTTTAACAACAGGTACTATGAACTCA

TTAACTTTAGCTAAGCATTTAAGTAAAAAATTTTCAATGAATAAAATGCTGCATTCTATAGGTT

ATCAATTTTTGATATCTTTAGAGTTTAGTAATTAACAAATTTGTTGGTTTATTATTGAACAAGT

GATTTCTTTGAATTTCCATTGTTTTATTGTTAAACAAATAATTTCCTTGAAATCGGATATATAT

AT AT AT ATGT AT AT AT AT AT AT AT AT AT AT AT AT AT AT ACA

(Template Construct 52; SEQ ID NO: 27334)

In an embodiment, an ssODN may be to correct a mutation, e.g., an intronic 3272-26bp (A- G) target site in the CFTR gene, and concomitantly introduce a silent mutation to disrupt subsequent Cas9 binding and cleavage. For example, the ssODN may include 5' and 3' homology arms as shown below. The 5' homology arm is shown as bold sequence, the inserted base to correct the intronic 3272-26bp (A- G) mutation is shown as lower case sequence, the silent sense mutation is shown as lower case underlined and italicized sequence, and the 3' homology arm is shown as no emphasis capitalized sequence.

ATATGATTATTCTAATTTAGTCTTTTTCAGGTACAAGATATTATGAAATTACATTTTGTGTTTA

TGTTATTTGCAaTGTTTTCTATccAAATATTTCACAGGCAGGAGTCCAATTTTCACTCATCTTG T T AC AAG C T T AAAAG GACTATGG

(Template Construct 53; SEQ ID NO: 27335)

The underlined C has been changed from a G to C at that position, so that wild-type CFTR is still transcribed, but the PAM sequence TGG has been modified to reduce or eliminate Cas9 cleavage at that locus.

Table 49 below provides exemplary template nucleic acids. In an embodiment, the template nucleic acid includes the 5' homology arm and the 3' homology arm of a row from Table 49. In other embodiments, a 5' homology arm from the first column can be combined with a 3' homology arm from Table 49. In each embodiment, a combination of the 5' and 3' homology arms include a replacement sequence, e.g., Cytosine-Thymine-Thymine (CTT) residues or a Guanine (G) residue. Table 49

1500 or more 1500 or more

1600 or more 1600 or more

1700 or more 1700 or more

1800 or more 1800 or more

1900 or more 1900 or more

1200 or more 1200 or more

At least 50 but not long enough to At least 50 but not long enough to include a repeated element. include a repeated element.

At least 100 but not long enough to At least 100 but not long enough to include a repeated element. include a repeated element.

At least 150 but not long enough to At least 150 but not long enough to include a repeated element. include a repeated element.

5 to 100 nucleotides 5 to 100 nucleotides

10 to 150 nucleotides 10 to 150 nucleotides

20 to 150 nucleotides 20 to 150 nucleotides

Template Construct No. 1

Template Construct No. 2

Template Construct No. 3

Template Construct No. 4

In an embodiment, a single or dual nickase eaCas9 is used to cleave the target DNA near the site of the mutation, or signature, to be modified, e.g., replaced. While not wishing to be bound by theory, in an embodiment, it is believed that the Cas9 mediated break induces HDR with the template nucleic acid to replace the target DNA sequence with the template sequence.

Targeted Knockin by cDNA Insertion

In an embodiment, homology-directed repair of the CFTR gene is used to target an intronic region between exons X and Y, wherein exons X and Y are any exons between exon 1 and exon 27, given that exon X and exon Y are adjacent and exon X has a lower number than exon Y, and deliver a Cas9 molecule, CRIPSR-gRNAs, and homology-directed repair templates that include homology arms, splice acceptor, contiguous coding sequence of exons (X+l) through exon 27 of CFTR gene and polyadenylation signal.

In an embodiment, one single strand break, two single strand breaks, one double strand break or two double strand breaks are introduced (e.g., positioned by one, two, three, or four gRNA molecule/s) at or in close proximity to a CF target knockin position in the CFTR gene. The CF target knockin position is the intronic region between CFTR exons X and Y. Altering the CF target knockin position refers to homology-directed repair of genomic sequence including the delivery of cDNA template of contiguous exons (X+l) through exon 27 of CFTR gene. Targeted knockin of CFTR cDNA leads to the cessation of production of mutant or truncated CFTR protein and results in the production of wild-type CFTR protein. Targeted knockin of CFTR cDNA prevents the development or progression of lung, gastrointestinal and/or reproductive disease in a subject due to the cessation of production of mutant CFTR protein and restoration of wild-type CFTR protein production. This approach cures and/or prevents the progression of lung, gastrointestinal and/or reproductive disease in any subject with CF or CF-like disease deficiency who has a mutation in exon (X+l) through exon 27 of the CFTR gene, or in any subject who has a mutation in an intronic or exonic region of the CFTR gene that is after intron X.

In an embodiment, homology-directed repair of the CFTR gene in any subject with CF mutations in exons 3 through 27 and introns 2 through 26 by targeting intronic region between exons 2 and 3 and with delivery of a homology-directed repair template including homology arms, splice acceptor, coding sequence of contiguous exons 3-27 of CFTR gene and

polyadenylation signal. The CF target position is the intronic region between exons 2 and 3. Altering the CF target position refers to homology-directed repair of genomic sequence including the delivery of cDNA template of exons 3-27 of CFTR gene. This approach cures and/or prevents the progression of lung, gastrointestinal and/or reproductive disease in any subject with CF or CF-like disease deficiency who has a mutation in exons 3-27 of the CFTR gene, or in any subject who has a mutation in an intronic or exonic region of the CFTR gene that is on or after the second intron, including but not limited to the following mutations: e.g., F508del,

G551D,G542X, N1303K, R117H, W1282X, R553X, c.3717+12191C>T, 2657+5G>A, or c.3140-26A>G.

In an embodiment, a cDNA insert construct comprises a 5' homology arm, a splice acceptor, a cDNA insert (e.g., CFTR exons 3 to 27, e.g., CFTR exons 11 to 27), a 3' homology arm, and a polyadenylation signal. Splice acceptors and polyadenylation signals are well known to one of skill in the art.

It is contemplated herein that, in an embodiment, a Cas9 molecule could potentially cleave cDNA insert constructs either prior to or following homology directed repair (e.g., homologous recombination), resulting in a possible non-homologous-end-joining event and further DNA sequence mutation at the chromosomal locus of interest. Therefore, to avoid cleavage of the cDNA insert sequence before and/or after Cas9-mediated homology directed repair, alternate versions of the homology arms may be used where silent mutations are introduced into a PAM. These silent mutations may disrupt Cas9 binding and cleavage, but not disrupt the amino acid sequence of the cDNA insert.

Exemplary template cDNA (also referred to herein as cDNA inserts) to introduce wild- type sequence, e.g., exons 3 to 27 of the CFTR gene, are provided. In an embodiment, the CRISPR-Cas9 binding site is CTCAAGTGATCTGCCCACCT TGG (SEQ ID NO: 27336) (PAM is underlined TGG).

In an embodiment, to insert CFTR cDNA (e.g., CFTR exons 3 to 27) into intron 2, and concomitantly introduce a silent mutation to disrupt subsequent Cas9 binding and cleavage, the homology arms, e.g., the 5' and 3' homology arms, may each comprise about 1000 base pairs (bp) of sequence flanking the most distal gRNAs (e.g., 1200bp of sequence on either side of the mutation). The 5' homology arm is shown as bold sequence, the CRISPR-Cas9 binding site is shown as italicized sequence, the PAM site is underlined, the silent sense mutation in the PAM is shown as lower case underlined sequence, and the 3' homology arm is shown as no emphasis capitalized sequence.

CAATCAAAAGGTTAGGATCCTTTTGATTGCCAGTGACAGAAACCCAATTTACTAGCTTAAGTAA ATAAAAGGAACGAATTTATTGGCTCATGAAGCCTGAACTATGTGAAGACCTAGGTGGAGAACTG GCCTTAGGAACTCAATGGGACCAAGGACTCAAATGCCACCTGGTGGCATTTGCCTTATGCTGGT TTTATTTTCTCAGACCGGACCAGCTTTCTACATAAAGTGGGTCCCTGGTTAGAACTCTTTGCTC CTATCTTTAAGGACCACGAAAGAAGGAGCCCTTTGTCCTTGGCTAAATGTGAAAAATCCCAGAG ACTCTTGAGTCATAGTGCTTACCCCTTGGGCCACTCATAGTCTAGAATGAACTAGGCTGAGTCT CGTGCCAACAGCACAGGCCTGATGCCAGATAAAAGGGTGAGTGAAGGGGGATAAAAAATAAGAC ATAGCTACTAAATTATTGCACCAAAGTAAAAACATTGAGTTGACTTGCAATTTGTTTCTTTTAA TTAAATTCATTTCCTTTTTTTGGCATTTTGAAGGCAAAGTAAGATATTAAACTTTATTTTTATT GATTTTATTCAAAGAATTAAGCTAGTGGGAGTAGCAGATTCACACTTCTAAGATCAAGGGCCAG CTTCTATTATTGAACACTTGGTGTGTGCAAATGCCATGAGGTAGGGATACTTTGTTTTGTTTTT TATTTTTTATTGGGTTCGATCTCTTTTGTTTATGATGTATCCCCAAGTGCCTAGAATAGGGCCT GGCATATGGTATATACTCAATAAATATTTGTTGAATGAATCCATGATGGAATGTGAAATGGCTA GCATTACATAGAAACCTGTAGCATTGCTGGAGAGATAAAATATATAAACATAATCCATTGCAGG TATATTGACAAGTTCAAAATAATATAATGGGTATTGAATATCTAAATGTTTGTTGTTGTTGTTG CTGTTGTTTTTGAGACAGAGTCTTGCTCTGTTGCCCAGGCTGGAGTGTAATGGTGCAATTTTGG CTCACTGCAAACTTCGTCTCCTGGGTTCAAGTGATTCTCCTGCCTCAGCCTCTCGAGTAGCTGG GTTTACAGGCACTCGCCACAATGCCTGGCTAATTTTTGTATTTTAGTAGATGTGGAGTTTCGCC ATGTTGGCCAGGCTGGTCTTGAACTCCTGACCrCAAGTGArCrGCCCACCrTaaCCTCCCAAAA TGCTGGGATTATAGGTGTGAGCCACTATGCCCAGCTTTGAATATCTAAGTTTTAATTGGATGCT GAGGGAATGATTAATCAGAGTAGGGCTGGGTTAATTGAAAAATGTGATACATTTGTATTTATGG CCAGATAGAGAACATGAATCTGAATTTGCAGAATTATCTGGCTTAACATTTTTTTCTTTCCAGT TTTCACTGTATCCCCCATGTTGATTCAATTTAAAAAATATACCTATTTTACTTCAATTCAACAA TGCTATGCCAGTACAAACCCATACGTTCTATTATTTTTGTTTTGTTTTGTTTTTGTATCTCCAC CCTGTTACTTCTTTTCTTATAAAATTGGTATTTGAAATTTATTGAAATATTTTGGAAGAGTGAC ATACCATTTTTGGTACTTTGTACCTCTGCACCCTTGGGAAGTGACCCTGGCTTCACATTTCATA ACTGCCTTGTGACCATGGCCCTCAAGTGGTTGCCAGATGGTTGAAGAACATTAACCTATCTGGC TCAATTTTGTGACCATGGATTGAATCCTCTACATAACTGCAGTGTGCAAACCACACATCCGTTC CAAGATTGTAGTCAGGATATGAACTTTTTAAGAATAAAACTTCTTCCCTTCTGATCTGGGCCTG GTATGTGGTCCTACTAGAACCACATCACCTACTCTTGGTGCTAACAATTTGTGGCACCAAGTTG TTCAAGTTTCACCCATTAAAGAAATTCCCCGACCTTGCCTTCTCCTCAGGTAACTACCCCATTC TATTTTTTCTTTCATAGCTAACATTCTCTGCTCTCCTGGTCTCTCTACTTCACTTTCATTTACA TCTCAGCTCCTGAAGTATGGTTTCCACCATGTTCCTAAAACTACATTGCCCAGGGTCACTAGAG ACCTCTTATGAAATATAACAACACCTTTCTACATTACTTCCGTGTGGACCACTTTTTCACATTG AACCCATTTTGTTGGTTTATGTACACACCCCTTCCTTGGCTTTCCCATCTGATCCATTTCTCCT TTGATGGAGAAGGTGAGTCTGCTCCATATTTAGCTTCTTACTCTGAGTAACCAAATGTTATGGA TGGGAGGTTAGCTCTGTGTGTGAGAGAAAGGTGGAGAAGCATGTGGGGAGGGAAATAGATGGGA AAAGGTAATTAGGCTTTATAGAAGGGCTCTCA

(SEQ ID NO: 27337) The underlined A has been changed from a G to A at that position so that wild-type CFTR is still transcribed, but the PAM sequence TGG has been modified to TAA to reduce or eliminate Cas9 cleavage at that locus.

In an embodiment, suitable sequence for the cDNA insert of CFTR exons 3 to 27, can be selected from (e.g., includes a portion of) or include the following sequence:

AGAATGGGATAGAGAGCTGGCTTCAAAGAAAAATCCTAAACTCATTAATGCCCTTCGGCGATGT TTTTTCTGGAGATTTATGTTCTATGGAATCTTTTTATATTTAGGGGAAGTCACCAAAGCAGTAC AGCCTCTCTTACTGGGAAGAATCATAGCTTCCTATGACCCGGATAACAAGGAGGAACGCTCTAT CGCGATTTATCTAGGCATAGGCTTATGCCTTCTCTTTATTGTGAGGACACTGCTCCTACACCCA GCCATTTTTGGCCTTCATCACATTGGAATGCAGATGAGAATAGCTATGTTTAGTTTGATTTATA AGAAGACTTTAAAGCTGTCAAGCCGTGTTCTAGATAAAATAAGTATTGGACAACTTGTTAGTCT CCTTTCCAACAACCTGAACAAATTTGATGAAGGACTTGCATTGGCACATTTCGTGTGGATCGCT CCTTTGCAAGTGGCACTCCTCATGGGGCTAATCTGGGAGTTGTTACAGGCGTCTGCCTTCTGTG GACTTGGTTTCCTGATAGTCCTTGCCCTTTTTCAGGCTGGGCTAGGGAGAATGATGATGAAGTA C AGAGAT C AGAGAGC T GGGAAGAT C AGT GAAAGAC T T GT GAT T ACC T CAGAAAT GAT T GAAAAT ATCCAATCTGTTAAGGCATACTGCTGGGAAGAAGCAATGGAAAAAATGATTGAAAACTTAAGAC AAACAGAACTGAAACTGACTCGGAAGGCAGCCTATGTGAGATACTTCAATAGCTCAGCCTTCTT CTTCTCAGGGTTCTTTGTGGTGTTTTTATCTGTGCTTCCCTATGCACTAATCAAAGGAATCATC CTCCGGAAAATATTCACCACCATCTCATTCTGCATTGTTCTGCGCATGGCGGTCACTCGGCAAT TTCCCTGGGCTGTACAAACATGGTATGACTCTCTTGGAGCAATAAACAAAATACAGGATTTCTT ACAAAAGCAAGAATATAAGACATTGGAATATAACTTAACGACTACAGAAGTAGTGATGGAGAAT GTAACAGCCTTCTGGGAGGAGGGATTTGGGGAATTATTTGAGAAAGCAAAACAAAACAATAACA ATAGAAAAACTTCTAATGGTGATGACAGCCTCTTCTTCAGTAATTTCTCACTTCTTGGTACTCC TGTCCTGAAAGATATTAATTTCAAGATAGAAAGAGGACAGTTGTTGGCGGTTGCTGGATCCACT GGAGCAGGCAAGACTTCACTTCTAATGGTGATTATGGGAGAACTGGAGCCTTCAGAGGGTAAAA TTAAGCACAGTGGAAGAATTTCATTCTGTTCTCAGTTTTCCTGGATTATGCCTGGCACCATTAA AGAAAATATCATCTTTGGTGTTTCCTATGATGAATATAGATACAGAAGCGTCATCAAAGCATGC CAACTAGAAGAGGACATCTCCAAGTTTGCAGAGAAAGACAATATAGTTCTTGGAGAAGGTGGAA TCACACTGAGTGGAGGTCAACGAGCAAGAATTTCTTTAGCAAGAGCAGTATACAAAGATGCTGA TTTGTATTTATTAGACTCTCCTTTTGGATACCTAGATGTTTTAACAGAAAAAGAAATATTTGAA AGCTGTGTCTGTAAACTGATGGCTAACAAAACTAGGATTTTGGTCACTTCTAAAATGGAACATT TAAAGAAAGCTGACAAAATATTAATTTTGCATGAAGGTAGCAGCTATTTTTATGGGACATTTTC AGAACTCCAAAATCTACAGCCAGACTTTAGCTCAAAACTCATGGGATGTGATTCTTTCGACCAA TTTAGTGCAGAAAGAAGAAATTCAATCCTAACTGAGACCTTACACCGTTTCTCATTAGAAGGAG ATGCTCCTGTCTCCTGGACAGAAACAAAAAAACAATCTTTTAAACAGACTGGAGAGTTTGGGGA AAAAAGGAAGAATTCTATTCTCAATCCAATCAACTCTATACGAAAATTTTCCATTGTGCAAAAG ACTCCCTTACAAATGAATGGCATCGAAGAGGATTCTGATGAGCCTTTAGAGAGAAGGCTGTCCT TAGTACCAGATTCTGAGCAGGGAGAGGCGATACTGCCTCGCATCAGCGTGATCAGCACTGGCCC CACGCTTCAGGCACGAAGGAGGCAGTCTGTCCTGAACCTGATGACACACTCAGTTAACCAAGGT CAGAACATTCACCGAAAGACAACAGCATCCACACGAAAAGTGTCACTGGCCCCTCAGGCAAACT TGACTGAACTGGATATATATTCAAGAAGGTTATCTCAAGAAACTGGCTTGGAAATAAGTGAAGA AATTAACGAAGAAGACTTAAAGGAGTGCTTTTTTGATGATATGGAGAGCATACCAGCAGTGACT ACATGGAACACATACCTTCGATATATTACTGTCCACAAGAGCTTAATTTTTGTGCTAATTTGGT GCTTAGTAATTTTTCTGGCAGAGGTGGCTGCTTCTTTGGTTGTGCTGTGGCTCCTTGGAAACAC TCCTCTTCAAGACAAAGGGAATAGTACTCATAGTAGAAATAACAGCTATGCAGTGATTATCACC AGCACCAGTTCGTATTATGTGTTTTACATTTACGTGGGAGTAGCCGACACTTTGCTTGCTATGG GATTCTTCAGAGGTCTACCACTGGTGCATACTCTAATCACAGTGTCGAAAATTTTACACCACAA AATGTTACATTCTGTTCTTCAAGCACCTATGTCAACCCTCAACACGTTGAAAGCAGGTGGGATT CTTAATAGATTCTCCAAAGATATAGCAATTTTGGATGACCTTCTGCCTCTTACCATATTTGACT TCATCCAGTTGTTATTAATTGTGATTGGAGCTATAGCAGTTGTCGCAGTTTTACAACCCTACAT CTTTGTTGCAACAGTGCCAGTGATAGTGGCTTTTATTATGTTGAGAGCATATTTCCTCCAAACC TCACAGCAACTCAAACAACTGGAATCTGAAGGCAGGAGTCCAATTTTCACTCATCTTGTTACAA GCTTAAAAGGACTATGGACACTTCGTGCCTTCGGACGGCAGCCTTACTTTGAAACTCTGTTCCA CAAAGCTCTGAATTTACATACTGCCAACTGGTTCTTGTACCTGTCAACACTGCGCTGGTTCCAA ATGAGAATAGAAATGATTTTTGTCATCTTCTTCATTGCTGTTACCTTCATTTCCATTTTAACAA CAGGAGAAGGAGAAGGAAGAGTTGGTATTATCCTGACTTTAGCCATGAATATCATGAGTACATT GCAGTGGGCTGTAAACTCCAGCATAGATGTGGATAGCTTGATGCGATCTGTGAGCCGAGTCTTT AAGTTCATTGACATGCCAACAGAAGGTAAACCTACCAAGTCAACCAAACCATACAAGAATGGCC AACTCTCGAAAGTTATGATTATTGAGAATTCACACGTGAAGAAAGATGACATCTGGCCCTCAGG GGGCCAAATGACTGTCAAAGATCTCACAGCAAAATACACAGAAGGTGGAAATGCCATATTAGAG AACATTTCCTTCTCAATAAGTCCTGGCCAGAGGGTGGGCCTCTTGGGAAGAACTGGATCAGGGA AGAGT AC T T T GT T AT CAGCT T T T T T GAGAC T AC T GAAC AC T G AAGG AG AAAT C C AG AT C G AT GG TGTGTCTTGGGATTCAATAACTTTGCAACAGTGGAGGAAAGCCTTTGGAGTGATACCACAGAAA GTATTTATTTTTTCTGGAACATTTAGAAAAAACTTGGATCCCTATGAACAGTGGAGTGATCAAG AAATATGGAAAGTTGCAGATGAGGTTGGGCTCAGATCTGTGATAGAACAGTTTCCTGGGAAGCT

TGACTTTGTCCTTGTGGATGGGGGCTGTGTCCTAAGCCATGGCCACAAGCAGTTGATGTGCTTG

GCTAGATCTGTTCTCAGTAAGGCGAAGATCTTGCTGCTTGATGAACCCAGTGCTCATTTGGATC

CAGTAACATACCAAATAATTAGAAGAACTCTAAAACAAGCATTTGCTGATTGCACAGTAATTCT

CTGTGAACACAGGATAGAAGCAATGCTGGAATGCCAACAATTTTTGGTCATAGAAGAGAACAAA

GTGCGGCAGTACGATTCCATCCAGAAACTGCTGAACGAGAGGAGCCTCTTCCGGCAAGCCATCA

GCCCCTCCGACAGGGTGAAGCTCTTTCCCCACCGGAACTCAAGCAAGTGCAAGTCTAAGCCCCA

GATTGCTGCTCTGAAAGAGGAGACAGAAGAAGAGGTGCAAGATACAAGGCTTTAG

(SEQ ID NO: 27338)

It is contemplated herein that one or both homology arms may be shortened to avoid including certain sequence repeat elements, e.g., Alu repeats, LINE elements. For example, a 5' homology arm may be shortened to avoid a sequence repeat element. In other embodiments, a 3' homology arm may be shortened to avoid a sequence repeat element. In some embodiments, both the 5' and the 3' homology arms may be shortened to avoid including certain sequence repeat elements.

In an embodiment, to insert CFTR cDNA (e.g., CFTR exons 3 to 27) into intron 2, and concomitantly introduce a silent mutation to disrupt subsequent Cas9 binding and cleavage, the homology arms, e.g., the 5' and 3' homology arms, may be shorted to approximately 500bp. The 5' homology arm is shown as bold sequence, the CRISPR-Cas9 binding site is shown as italicized sequence, the PAM site is underlined, the silent sense mutation in the PAM is shown as lower case underlined sequence, and the 3' homology arm is shown as no emphasis capitalized sequence.

TTTTTATTTTTTATTGGGTTCGATCTCTTTTGTTTATGATGTATCCCCAAGTGCCTAGAATAGG GCCTGGCATATGGTATATACTCAATAAATATTTGTTGAATGAATCCATGATGGAATGTGAAATG GCTAGCATTACATAGAAACCTGTAGCATTGCTGGAGAGATAAAATATATAAACATAATCCATTG CAGGTATATTGACAAGTTCAAAATAATATAATGGGTATTGAATATCTAAATGTTTGTTGTTGTT GTTGCTGTTGTTTTTGAGACAGAGTCTTGCTCTGTTGCCCAGGCTGGAGTGTAATGGTGCAATT TTGGCTCACTGCAAACTTCGTCTCCTGGGTTCAAGTGATTCTCCTGCCTCAGCCTCTCGAGTAG CTGGGTTTACAGGCACTCGCCACAATGCCTGGCTAATTTTTGTATTTTAGTAGATGTGGAGTTT CGCCATGTTGGCCAGGCTGGTCTTGAACTCCTGACCrCAAGTGArCrGCCCACCrTaaCCTCCC AAAATGCTGGGATTATAGGTGTGAGCCACTATGCCCAGCTTTGAATATCTAAGTTTTAATTGGA TGCTGAGGGAATGATTAATCAGAGTAGGGCTGGGTTAATTGAAAAATGTGATACATTTGTATTT

ATGGCCAGATAGAGAACATGAATCTGAATTTGCAGAATTATCTGGCTTAACATTTTTTTCTTTC

CAGTTTTCACTGTATCCCCCATGTTGATTCAATTTAAAAAATATACCTATTTTACTTCAATTCA

ACAATGCTATGCCAGTACAAACCCATACGTTCTATTATTTTTGTTTTGTTTTGTTTTTGTATCT

CCACCCTGTTACTTCTTTTCTTATAAAATTGGTATTTGAAATTTATTGAAATATTTTGGAAGAG

TGACATACCATTTTTGGTACTTTGTACCTCTGCACCCTTGGGAAGTGACCCTGGCTTCACATTT

CATAACTGCCTTGTGACCATGGCCCTCAAGTGGTTGCCAG

(SEQ ID NO: 27339)

The underlined A has been changed from a G to A at that position so that wild-type CFTR is still transcribed, but the PAM sequence TGG has been modified to TAA to reduce or eliminate Cas9 cleavage at that locus.

Exemplary template cDNA (also referred to herein as cDNA inserts) to introduce wild- type sequence, e.g., exons 11 to 27 of the CFTR gene, are provided. In an embodiment, the CRISPPv-Cas9 binding site is AGTGAATGAATGTGGTATCCCGG (SEQ ID NO: 27340)(PAM is underlined CGG).

In an embodiment, to insert CFTR cDNA (e.g., CFTR exons 11 to 27) into intron 10, and concomitantly introduce a silent mutation to disrupt subsequent Cas9 binding and cleavage, the homology arms, e.g., the 5' and 3' homology arms, may each comprise about 1000 base pairs (bp) of sequence flanking the most distal gRNAs (e.g., 1200bp of sequence on either side of the mutation). The 5' homology arm is shown as bold sequence, the CRISPR-Cas9 binding site is shown as italicized sequence, the PAM site is underlined, the silent sense mutation in the PAM is shown as lower case underlined sequence, and the 3' homology arm is shown as no emphasis capitalized sequence.

CTAAATAGAGTGCTGATTTCCCCACAGCATTACTAACAGATGATATTATCTAATTTAAAAAGTT TCTCATCTTATAGGGAAAATAGTATGTCAATGTATTCTTAACTTGCATTTCTTTTATTATAAGT AGTGTAAAATATCATTTCAACTTATACACAGGAGGAATTTCTCTCTATATAAAGTGATCCTAGA ATCATAATGAAAAATATCACCAACTCATTAGGAAAATGTACAAAGGATTGAATAGATATCTCAT CAAAAATAAAAATATAAGTGGCCTTTAAACATTGAAAGGTAACATTTGAACAAAGACTTGCAGG AGGTGAGGGATTAGGGAATGCAGACTCTGGGAAGAGTCTTCCAAGTAGCAGGTGAAGCAAGTGC AAAGCTTTCAGATGGGACTGACTATACCTGTCTGGTTTGAAGAACAGTAAGGAGGTCACTGAGG CTGGCATAGAGTAAGACAGGGAGGGTAGAATACTGTCAGAGAAGTAATCGGCGGTGGAGGTAGG GGGTAAACCATAAAGTGCTCGTAAAGACTAAGGCTTATTTCTCTGGGTGAGATTAGAGGCCACT

GGAGAGTTTTAAACAGAAGTAACAGGGCCACTTTGGCTAATGTTTTTAGGCTATTCTGTAGGGA

GACAAGGGAGGAAGCAAGGAGATGAGTTAGGAGTCTATTGTGCCAGTTCAGGCAAGTGATGATG

GTGGCTTGATCCAGGTAGTAGTGGAAGTAGTATAGTAGGAAGTGATCAGATTCAGGACATGCTT

TGAAGGAAGATCCAATAGGATTAATGGATAAGTTGAACAATGGCATATGAGAAAAGTCACAGAG

GAGTCAAAGATGATTCCAAGCTTTCTGGACTGAGTAACTGGAAGGATAAATGTGCCGTTTACTA

GAAAGATAATGGGAGAAACAGGTTTTGGATGGAGCTTGGTTTGGGAATATTAAGTTTGAAATGC

CTATTTGACATCCAAATAGAGATGTTAGTTGGATGTACAAGTCTAGTTTCAAGGAAGAGGGGGC

TGGTAGTGTGAAGATGGGGCTGGATAAGATTCTAAAGGAAAGAGGGTTGATAAGAAGAGAAAGG

GGTGTAGGGGTTAGCCTAAGGGCATTCTAAGTATTAGAGGTTAAGGAGGTGGGTGAAGAAAACC

CAATAAAATAAAAGTCTGAGAAGACAAAGCTAGTGAATGAATGTGGTATCCCttAACCCAACTG

ATGTCAAGCAGAAGGGTGTTATCAACTAGGTCAAATGCTCATTCATCAAGTAAGATGAAACTGT

TATAATTAACCGGTGTCTTCTGAAATACGGAGATAACTCGTGACTTAATGAAAGCAATAGTAGA

GAAGGTCAAACTTGACCAGAATGAAATTAGAAAGAATAAGAGGAAAGAAAAGACCAAATACAGA

CAACCATTGATGCCTTATTCTTTTGATATACTCCTGGAGTCCACTTGCTAATACAATTGACCCT

TAAACAATACAGGCTTGAACTGCATGGGTCCACTTATTTGTGAATTTTTTTTCAGTTAATACAT

TGGAAAATTTTTGGGGTTTTTTGACAATTTGAAAAAACTCACAAACTGTCTAGCCTAGAAATAC

CGAGAAAATTAAGAAAAAGTAAGATATGCCATGAATGCATAAAATATATGTAGACACTAGCCTA

TTTTATCATTTGCTACTATAAAATATACACAATCTATTATAAAAAGTTAAAATTTATCAAAACT

TAACACACACTAACACCTACCCTACCTGGCACCATTCACAGTAAAGAGAAATGTAAATAAACAT

AAAAATGTAGTATTAAACCATAATGGCATAAAACTAATTGTAGTACATATGGTACTACTGTAAT

AATTTGGAAGCCACTTCCTGTTGCTATTACGGTAAGCTCAAGCATTGTGGATAGCCATTTAAAA

CACCACGTGATGCTAATCATCTCCGTGTGAGCAGTTCTCTCTCCAGTAAATTGCATATTGCAGT

AAAAAGTGATCTCTAGTGGTTCTCGCATATTTTTCATCATGTTTAGTGCAATGCCATAAACCTT

GAATAACATCAAGCAATCCATACAAAGTGCCACTAGTGATGCACGGAAAAGTTGTAACAGTACA

AGAAAAAAGTTGAGTTGCTTGGTATTTACCATATATTGAGGTCTGCAGCTACAGTTGCCTGCAA

TTTCGAGATAAATGAACCCAGTATAAAGACTGTTGTAACAAAAGAAAAGAAAATGTGAAACCAT

CAGTGCAGCTATGCCAGCAGGTGTGAAGTCTTGCACTTTTTGCAAAATACAAAATATGAAATAT

GTGTTAATTGACTGTTTATGTTATCTGTAAGGTTTCCACTCAACAATAGGCTATTAGTAGTTAA

GTTTTTGTGGAGTCAAAAATTATACGTGGATT

(SEQ ID NO: 27341) The underlined T has been changed from a G to T at that position so that wild-type CFTR is still transcribed, but the PAM sequence CGG has been modified to CTT to reduce or eliminate Cas9 cleavage at that locus.

In an embodiment, suitable sequence for the cDNA insert of CFTR exons 11 to 27, can be selected from (e.g., includes a portion of) or include the following sequence:

ACTTCACTTCTAATGGTGATTATGGGAGAACTGGAGCCTTCAGAGGGTAAAATTAAGCACAGTG GAAGAATTTCATTCTGTTCTCAGTTTTCCTGGATTATGCCTGGCACCATTAAAGAAAATATCAT CTTTGGTGTTTCCTATGATGAATATAGATACAGAAGCGTCATCAAAGCATGCCAACTAGAAGAG GACATCTCCAAGTTTGCAGAGAAAGACAATATAGTTCTTGGAGAAGGTGGAATCACACTGAGTG GAGGTCAACGAGCAAGAATTTCTTTAGCAAGAGCAGTATACAAAGATGCTGATTTGTATTTATT AGACTCTCCTTTTGGATACCTAGATGTTTTAACAGAAAAAGAAATATTTGAAAGCTGTGTCTGT AAACTGATGGCTAACAAAACTAGGATTTTGGTCACTTCTAAAATGGAACATTTAAAGAAAGCTG ACAAAATATTAATTTTGCATGAAGGTAGCAGCTATTTTTATGGGACATTTTCAGAACTCCAAAA TCTACAGCCAGACTTTAGCTCAAAACTCATGGGATGTGATTCTTTCGACCAATTTAGTGCAGAA AGAAGAAATTCAATCCTAACTGAGACCTTACACCGTTTCTCATTAGAAGGAGATGCTCCTGTCT CCTGGACAGAAACAAAAAAACAATCTTTTAAACAGACTGGAGAGTTTGGGGAAAAAAGGAAGAA TTCTATTCTCAATCCAATCAACTCTATACGAAAATTTTCCATTGTGCAAAAGACTCCCTTACAA ATGAATGGCATCGAAGAGGATTCTGATGAGCCTTTAGAGAGAAGGCTGTCCTTAGTACCAGATT CTGAGCAGGGAGAGGCGATACTGCCTCGCATCAGCGTGATCAGCACTGGCCCCACGCTTCAGGC ACGAAGGAGGCAGTCTGTCCTGAACCTGATGACACACTCAGTTAACCAAGGTCAGAACATTCAC CGAAAGACAACAGCATCCACACGAAAAGTGTCACTGGCCCCTCAGGCAAACTTGACTGAACTGG ATATATATTCAAGAAGGTTATCTCAAGAAACTGGCTTGGAAATAAGTGAAGAAATTAACGAAGA AGACTTAAAGGAGTGCTTTTTTGATGATATGGAGAGCATACCAGCAGTGACTACATGGAACACA TACCTTCGATATATTACTGTCCACAAGAGCTTAATTTTTGTGCTAATTTGGTGCTTAGTAATTT TTCTGGCAGAGGTGGCTGCTTCTTTGGTTGTGCTGTGGCTCCTTGGAAACACTCCTCTTCAAGA CAAAGGGAATAGTACTCATAGTAGAAATAACAGCTATGCAGTGATTATCACCAGCACCAGTTCG TATTATGTGTTTTACATTTACGTGGGAGTAGCCGACACTTTGCTTGCTATGGGATTCTTCAGAG GTCTACCACTGGTGCATACTCTAATCACAGTGTCGAAAATTTTACACCACAAAATGTTACATTC TGTTCTTCAAGCACCTATGTCAACCCTCAACACGTTGAAAGCAGGTGGGATTCTTAATAGATTC TCCAAAGATATAGCAATTTTGGATGACCTTCTGCCTCTTACCATATTTGACTTCATCCAGTTGT TATTAATTGTGATTGGAGCTATAGCAGTTGTCGCAGTTTTACAACCCTACATCTTTGTTGCAAC AGTGCCAGTGATAGTGGCTTTTATTATGTTGAGAGCATATTTCCTCCAAACCTCACAGCAACTC AAACAACTGGAATCTGAAGGCAGGAGTCCAATTTTCACTCATCTTGTTACAAGCTTAAAAGGAC

TATGGACACTTCGTGCCTTCGGACGGCAGCCTTACTTTGAAACTCTGTTCCACAAAGCTCTGAA

TTTACATACTGCCAACTGGTTCTTGTACCTGTCAACACTGCGCTGGTTCCAAATGAGAATAGAA

ATGATTTTTGTCATCTTCTTCATTGCTGTTACCTTCATTTCCATTTTAACAACAGGAGAAGGAG

AAGGAAGAGTTGGTATTATCCTGACTTTAGCCATGAATATCATGAGTACATTGCAGTGGGCTGT

AAACTCCAGCATAGATGTGGATAGCTTGATGCGATCTGTGAGCCGAGTCTTTAAGTTCATTGAC

ATGCCAACAGAAGGTAAACCTACCAAGTCAACCAAACCATACAAGAATGGCCAACTCTCGAAAG

TTATGATTATTGAGAATTCACACGTGAAGAAAGATGACATCTGGCCCTCAGGGGGCCAAATGAC

TGTCAAAGATCTCACAGCAAAATACACAGAAGGTGGAAATGCCATATTAGAGAACATTTCCTTC

TCAATAAGTCCTGGCCAGAGGGTGGGCCTCTTGGGAAGAACTGGATCAGGGAAGAGTACTTTGT

TATCAGCTTTTTTGAGACTACTGAACACTGAAGGAGAAATCCAGATCGATGGTGTGTCTTGGGA

TTCAATAACTTTGCAACAGTGGAGGAAAGCCTTTGGAGTGATACCACAGAAAGTATTTATTTTT

TCTGGAACATTTAGAAAAAACTTGGATCCCTATGAACAGTGGAGTGATCAAGAAATATGGAAAG

TTGCAGATGAGGTTGGGCTCAGATCTGTGATAGAACAGTTTCCTGGGAAGCTTGACTTTGTCCT

TGTGGATGGGGGCTGTGTCCTAAGCCATGGCCACAAGCAGTTGATGTGCTTGGCTAGATCTGTT

CTCAGTAAGGCGAAGATCTTGCTGCTTGATGAACCCAGTGCTCATTTGGATCCAGTAACATACC

AAATAATTAGAAGAACTCTAAAACAAGCATTTGCTGATTGCACAGTAATTCTCTGTGAACACAG

GATAGAAGCAATGCTGGAATGCCAACAATTTTTGGTCATAGAAGAGAACAAAGTGCGGCAGTAC

GATTCCATCCAGAAACTGCTGAACGAGAGGAGCCTCTTCCGGCAAGCCATCAGCCCCTCCGACA

GGGTGAAGCTCTTTCCCCACCGGAACTCAAGCAAGTGCAAGTCTAAGCCCCAGATTGCTGCTCT

GAAAGAGGAGACAGAAGAAGAGGTGCAAGATACAAGGCTTTAG

(SEQ ID NO: 27342)

In an embodiment, to insert CFTR cDNA (e.g., CFTR exons 11 to 27) into intron 10, and concomitantly introduce a silent mutation to disrupt subsequent Cas9 binding and cleavage, the homology arms, e.g., the 5' and 3' homology arms, may be shorted to approximately 500bp. The 5' homology arm is shown as bold sequence, the CRISPR-Cas9 binding site is shown as italicized sequence, the PAM site is underlined, the silent sense mutation in the PAM is shown as lower case underlined sequence, and the 3' homology arm is shown as no emphasis capitalized sequence.

GATGGTGGCTTGATCCAGGTAGTAGTGGAAGTAGTATAGTAGGAAGTGATCAGATTCAGGACAT GCTTTGAAGGAAGATCCAATAGGATTAATGGATAAGTTGAACAATGGCATATGAGAAAAGTCAC AGAGGAGTCAAAGATGATTCCAAGCTTTCTGGACTGAGTAACTGGAAGGATAAATGTGCCGTTT

ACTAGAAAGATAATGGGAGAAACAGGTTTTGGATGGAGCTTGGTTTGGGAATATTAAGTTTGAA

ATGCCTATTTGACATCCAAATAGAGATGTTAGTTGGATGTACAAGTCTAGTTTCAAGGAAGAGG

GGGCTGGTAGTGTGAAGATGGGGCTGGATAAGATTCTAAAGGAAAGAGGGTTGATAAGAAGAGA

AAGGGGTGTAGGGGTTAGCCTAAGGGCATTCTAAGTATTAGAGGTTAAGGAGGTGGGTGAAGAA

AACCCAATAAAATAAAAGTCTGAGAAGACAAAGCTAGrGAA TGAA TGTGGTA TCCCtt AACCCA

ACTGATGTCAAGCAGAAGGGTGTTATCAACTAGGTCAAATGCTCATTCATCAAGTAAGATGAAA

CTGTTATAATTAACCGGTGTCTTCTGAAATACGGAGATAACTCGTGACTTAATGAAAGCAATAG

TAGAGAAGGTCAAACTTGACCAGAATGAAATTAGAAAGAATAAGAGGAAAGAAAAGACCAAATA

CAGACAACCATTGATGCCTTATTCTTTTGATATACTCCTGGAGTCCACTTGCTAATACAATTGA

CCCTTAAACAATACAGGCTTGAACTGCATGGGTCCACTTATTTGTGAATTTTTTTTCAGTTAAT

ACATTGGAAAATTTTTGGGGTTTTTTGACAATTTGAAAAAACTCACAAACTGTCTAGCCTAGAA

ATACCGAGAAAATTAAGAAAAAGTAAGATATGCCATGAATGCATAAAATATATGTAGACACTAG

CCTATTTTATCATTTGCTACTATAAAATATACACAATCTA

(SEQ ID NO: 27343)

The underlined T has been changed from a G to T at that position so that wild-type CFTR is still transcribed, but the PAM sequence CGG has been modified to CTT to reduce or eliminate Cas9 cleavage at that locus.

V.2 NHEJ Approaches for Gene Targeting

As described herein, nuclease-induced non-homologous end-joining (NHEJ) can be used to target gene-specific knockouts. Nuclease-induced NHEJ can also be used to remove (e.g., delete) sequence insertions in a gene of interest.

While not wishing to be bound by theory, it is believed that, in an embodiment, the genomic alterations associated with the methods described herein rely on nuclease-induced NHEJ and the error-prone nature of the NHEJ repair pathway. NHEJ repairs a double-strand break in the DNA by joining together the two ends; however, generally, the original sequence is restored only if two compatible ends, exactly as they were formed by the double-strand break, are perfectly ligated. The DNA ends of the double-strand break are frequently the subject of enzymatic processing, resulting in the addition or removal of nucleotides, at one or both strands, prior to rejoining of the ends. This results in the presence of insertion and/or deletion (indel) mutations in the DNA sequence at the site of the NHEJ repair. Two-thirds of these mutations typically alter the reading frame and, therefore, produce a non-functional protein. Additionally, mutations that maintain the reading frame, but which insert or delete a significant amount of sequence, can destroy functionality of the protein. This is locus dependent as mutations in critical functional domains are likely less tolerable than mutations in non-critical regions of the protein.

The indel mutations generated by NHEJ are unpredictable in nature; however, at a given break site certain indel sequences are favored and are over represented in the population, likely due to small regions of microhomology. The lengths of deletions can vary widely; most commonly in the 1-50 bp range, but they can easily reach greater than 100-200 bp. Insertions tend to be shorter and often include short duplications of the sequence immediately surrounding the break site. However, it is possible to obtain large insertions, and in these cases, the inserted sequence has often been traced to other regions of the genome or to plasmid DNA present in the cells.

Because NHEJ is a mutagenic process, it can also be used to delete small sequence motifs as long as the generation of a specific final sequence is not required. If a double- strand break is targeted near to a short target sequence, the deletion mutations caused by the NHEJ repair often span, and therefore remove, the unwanted nucleotides. For the deletion of larger DNA segments, introducing two double-strand breaks, one on each side of the sequence, can result in NHEJ between the ends with removal of the entire intervening sequence. Both of these approaches can be used to delete specific DNA sequences; however, the error-prone nature of NHEJ may still produce indel mutations at the site of repair.

Both double strand cleaving eaCas9 molecules and single strand, or nickase, eaCas9 molecules can be used in the methods and compositions described herein to generate NHEJ- mediated indels. NHEJ-mediated indels targeted to the gene, e.g., a coding region, e.g., an early coding region of a gene of interest can be used to knockout (i.e., eliminate expression of) a gene of interest. For example, early coding region of a gene of interest includes sequence

immediately following a transcription start site, within a first exon of the coding sequence, or within 500 bp of the transcription start site (e.g., less than 500, 450, 400, 350, 300, 250, 200, 150, 100 or 50 bp). Placement of double strand or single strand breaks relative to the target position In an embodiment, in which a gRNA and Cas9 nuclease generate a double strand break for the purpose of inducing NHEJ-mediated indels, a gRNA, e.g., a unimolecular (or chimeric) or modular gRNA molecule, is configured to position one double-strand break in close proximity to a nucleotide of the target position. In an embodiment, the cleavage site is between 0-30 bp away from the target position (e.g., less than 30, 25, 20, 15, 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1 bp from the target position).

In an embodiment, in which two gRNAs complexing with Cas9 nickases induce two single strand breaks for the purpose of inducing NHEJ-mediated indels, two gRNAs, e.g., independently, unimolecular (or chimeric) or modular gRNA, are configured to position two single-strand breaks to provide for NHEJ repair a nucleotide of the target position. In an embodiment, the gRNAs are configured to position cuts at the same position, or within a few nucleotides of one another, on different strands, essentially mimicking a double strand break. In an embodiment, the closer nick is between 0-30 bp away from the target position (e.g., less than 30, 25, 20, 15, 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1 bp from the target position), and the two nicks are within 25-55 bp of each other (e.g., between 25 to 50, 25 to 45, 25 to 40, 25 to 35, 25 to 30, 50 to 55, 45 to 55, 40 to 55, 35 to 55, 30 to 55, 30 to 50, 35 to 50, 40 to 50 , 45 to 50, 35 to 45, or 40 to 45 bp) and no more than 100 bp away from each other (e.g., no more than 90, 80, 70, 60, 50, 40, 30, 20 or 10 bp). In an embodiment, the gRNAs are configured to place a single strand break on either side of a nucleotide of the target position.

Both double strand cleaving eaCas9 molecules and single strand, or nickase, eaCas9 molecules can be used in the methods and compositions described herein to generate breaks both sides of a target position. Double strand or paired single strand breaks may be generated on both sides of a target position to remove the nucleic acid sequence between the two cuts (e.g., the region between the two breaks in deleted). In one embodiment, two gRNAs, e.g.,

independently, unimolecular (or chimeric) or modular gRNA, are configured to position a double-strand break on both sides of a target position. In an alternate embodiment, three gRNAs, e.g., independently, unimolecular (or chimeric) or modular gRNA, are configured to position a double strand break (i.e., one gRNA complexes with a cas9 nuclease) and two single strand breaks or paired single stranded breaks (i.e., two gRNAs complex with Cas9 nickases) on either side of the target position. In another embodiment, four gRNAs, e.g., independently, unimolecular (or chimeric) or modular gRNA, are configured to generate two pairs of single stranded breaks (i.e., two pairs of two gRNAs complex with Cas9 nickases) on either side of the target position. The double strand break(s) or the closer of the two single strand nicks in a pair will ideally be within 0-500 bp of the target position (e.g., no more than 450, 400, 350, 300, 250, 200, 150, 100, 50 or 25 bp from the target position). When nickases are used, the two nicks in a pair are within 25-55 bp of each other (e.g., between 25 to 50, 25 to 45, 25 to 40, 25 to 35, 25 to 30, 50 to 55, 45 to 55, 40 to 55, 35 to 55, 30 to 55, 30 to 50, 35 to 50, 40 to 50 , 45 to 50, 35 to 45, or 40 to 45 bp) and no more than 100 bp away from each other (e.g., no more than 90, 80, 70, 60, 50, 40, 30, 20 or 10 bp).

V.3 Single- Strand Annealing

Single strand annealing (SSA) is another DNA repair process that repairs a double-strand break between two repeat sequences present in a target nucleic acid. Repeat sequences utilized by the SSA pathway are generally greater than 30 nucleotides in length. Resection at the break ends occurs to reveal repeat sequences on both strands of the target nucleic acid. After resection, single strand overhangs containing the repeat sequences are coated with RPA protein to prevent the repeats sequences from inappropriate annealing, e.g., to themselves. RAD52 binds to and each of the repeat sequences on the overhangs and aligns the sequences to enable the annealing of the complementary repeat sequences. After annealing, the single-strand flaps of the overhangs are cleaved. New DNA synthesis fills in any gaps, and ligation restores the DNA duplex. As a result of the processing, the DNA sequence between the two repeats is deleted. The length of the deletion can depend on many factors including the location of the two repeats utilized, and the pathway or processivity of the resection.

In contrast to HDR pathways, SSA does not require a template nucleic acid to alter or correct a target nucleic acid sequence. Instead, the complementary repeat sequence is utilized.

V. 4 Other DNA Repair Pathways

SSBR (single strand break repair)

Single- stranded breaks (SSB) in the genome are repaired by the SSBR pathway, which is a distinct mechanism from the DSB repair mechanisms discussed above. The SSBR pathway has four major stages: SSB detection, DNA end processing, DNA gap filling, and DNA ligation. A more detailed explanation is given in Caldecott, Nature Reviews Genetics 9, 619-631 (August 2008), and a summary is given here.

In the first stage, when a SSB forms, PARP1 and/or PARP2 recognize the break and recruit repair machinery. The binding and activity of PARP1 at DNA breaks is transient and it seems to accelerate SSBr by promoting the focal accumulation or stability of SSBr protein complexes at the lesion. Arguably the most important of these SSBr proteins is XRCCl, which functions as a molecular scaffold that interacts with, stabilizes, and stimulates multiple enzymatic components of the SSBr process including the protein responsible for cleaning the DNA 3' and 5' ends. For instance, XRCCl interacts with several proteins (DNA polymerase beta, PNK, and three nucleases, APE1, APTX, and APLF) that promote end processing. APE1 has endonuclease activity. APLF exhibits endonuclease and 3' to 5' exonuclease activities. APTX has endonuclease and 3' to 5' exonuclease activity.

This end processing is an important stage of SSBR since the 3'- and/or 5 '-termini of most, if not all, SSBs are 'damaged'. End processing generally involves restoring a damaged 3'- end to a hydroxylated state and and/or a damaged 5' end to a phosphate moiety, so that the ends become ligation-competent. Enzymes that can process damaged 3' termini include PNKP, APE1, and TDP1. Enzymes that can process damaged 5' termini include PNKP, DNA polymerase beta, and APTX. LIG3 (DNA ligase III) can also participate in end processing. Once the ends are cleaned, gap filling can occur.

At the DNA gap filling stage, the proteins typically present are PARP1, DNA polymerase beta, XRCCl, FEN1 (flap endonculease 1), DNA polymerase delta/epsilon, PCNA, and LIG1. There are two ways of gap filling, the short patch repair and the long patch repair. Short patch repair involves the insertion of a single nucleotide that is missing. At some SSBs, "gap filling" might continue displacing two or more nucleotides (displacement of up to 12 bases have been reported). FEN1 is an endonuclease that removes the displaced 5'-residues. Multiple DNA polymerases, including Pol β , are involved in the repair of SSBs, with the choice of DNA polymerase influenced by the source and type of SSB.

In the fourth stage, a DNA ligase such as LIG1 (Ligase I) or LIG3 (Ligase III) catalyzes joining of the ends. Short patch repair uses Ligase III and long patch repair uses Ligase I.

Sometimes, SSBR is replication-coupled. This pathway can involve one or more of CtIP, MRN, ERCC1, and FEN1. Additional factors that may promote SSBR include: aPARP, PARP1, PARP2, PARG, XRCC1, DNA polymerase b, DNA polymerase d, DNA polymerase e, PCNA, LIGl, PNK, PNKP, APEl, APTX, APLF, TDPl, LIG3, FENl, CtIP, MRN, and ERCCl.

MMR (mismatch repair)

Cells contain three excision repair pathways: MMR, BER, and NER. The excision repair pathways hace a common feature in that they typically recognize a lesion on one strand of the DNA, then exo/endonucleaseases remove the lesion and leave a 1-30 nucleotide gap that is sub- sequentially filled in by DNA polymerase and finally sealed with ligase. A more complete picture is given in Li, Cell Research (2008) 18:85-98, and a summary is provided here.

Mismatch repair (MMR) operates on mispaired DNA bases.

The MSH2/6 or MSH2/3 complexes both have ATPases activity that plays an important role in mismatch recognition and the initiation of repair. MSH2/6 preferentially recognizes base- base mismatches and identifies mispairs of 1 or 2 nucleotides, while MSH2/3 preferentially recognizes larger ID mispairs.

hMLHl heterodimerizes with hPMS2 to form hMutL which possesses an ATPase activity and is important for multiple steps of MMR. It possesses a PCNA/replication factor C (RFC)-dependent endonuclease activity which plays an important role in 3 ' nick-directed MMR involving EXOl. (EXOl is a participant in both HR and MMR.) It regulates termination of mismatch-provoked excision. Ligase I is the relevant ligase for this pathway. Additional factors that may promote MMR include: EXOl, MSH2, MSH3, MSH6, MLH1, PMS2, MLH3, DNA Pol d, RPA, HMGB1, RFC, and DNA ligase I.

Base excision repair (BER)

The base excision repair (BER) pathway is active throughout the cell cycle; it is responsible primarily for removing small, non-helix-distorting base lesions from the genome. In contrast, the related Nucleotide Excision Repair pathway (discussed in the next section) repairs bulky helix-distorting lesions. A more detailed explanation is given in Caldecott, Nature

Reviews Genetics 9, 619-631 (August 2008), and a summary is given here.

Upon DNA base damage, base excision repair (BER) is initiated and the process can be simplified into five major steps: (a) removal of the damaged DNA base; (b) incision of the subsequent a basic site; (c) clean-up of the DNA ends; (d) insertion of the correct nucleotide into the repair gap; and (e) ligation of the remaining nick in the DNA backbone. These last steps are similar to the SSBR.

In the first step, a damage- specific DNA glycosylase excises the damaged base through cleavage of the N-glycosidic bond linking the base to the sugar phosphate backbone. Then AP endonuclease-1 (APE1) or bifunctional DNA glycosylases with an associated lyase activity incised the phosphodiester backbone to create a DNA single strand break (SSB). The third step of BER involves cleaning-up of the DNA ends. The fourth step in BER is conducted by Pol β that adds a new complementary nucleotide into the repair gap and in the final step

XRCCl/Ligase III seals the remaining nick in the DNA backbone. This completes the short- patch BER pathway in which the majority (-80%) of damaged DNA bases are repaired.

However, if the 5⁷ -ends in step 3 are resistant to end processing activity, following one nucleotide insertion by Pol β there is then a polymerase switch to the replicative DNA polymerases, Pol δ/ε, which then add -2-8 more nucleotides into the DNA repair gap. This creates a 5 ' -flap structure, which is recognized and excised by flap endonuclease-1 (FEN-1) in association with the processivity factor proliferating cell nuclear antigen (PCNA). DNA ligase I then seals the remaining nick in the DNA backbone and completes long-patch BER. Additional factors that may promote the BER pathway include: DNA glycosylase, APE1, Polb, Pold, Pole, XRCC1, Ligase III, FEN-1, PCNA, RECQL4, WRN, MYH, PNKP, and APTX.

Nucleotide excision repair (NER)

Nucleotide excision repair (NER) is an important excision mechanism that removes bulky helix-distorting lesions from DNA. Additional details about NER are given in Marteijn et al., Nature Reviews Molecular Cell Biology 15, 465-481 (2014), and a summary is given here. NER a broad pathway encompassing two smaller pathways: global genomic NER (GG-NER) and transcription coupled repair NER (TC-NER). GG-NER and TC-NER use different factors for recognizing DNA damage. However, they utilize the same machinery for lesion incision, repair, and ligation.

Once damage is recognized, the cell removes a short single- stranded DNA segment that contains the lesion. Endonucleases XPF/ERCC1 and XPG (encoded by ERCC5) remove the lesion by cutting the damaged strand on either side of the lesion, resulting in a single-strand gap of 22-30 nucleotides. Next, the cell performs DNA gap filling synthesis and ligation. Involved in this process are: PCNA, RFC, DNA Pol δ, DNA Pol ε or DNA Pol κ, and DNA ligase I or XRCCl/Ligase III. Replicating cells tend to use DNA pol ε and DNA ligase I, while non- replicating cells tend to use DNA Pol δ, DNA Pol κ, and the XRCC1/ Ligase III complex to perform the ligation step.

NER can involve the following factors: XPA-G, POLH, XPF, ERCC1, XPA-G, and LIG1. Transcription-coupled NER (TC-NER) can involve the following factors: CSA, CSB, XPB, XPD, XPG, ERCC1, and TTDA. Additional factors that may promote the NER repair pathway include XPA-G, POLH, XPF, ERCC1, XPA-G, LIG1, CSA, CSB, XPA, XPB, XPC, XPD, XPF, XPG, TTDA, UVSSA, USP7, CETN2, RAD23B, UV-DDB, CAK subcomplex, RPA, and PCNA.

Interstrand Crosslink (ICL)

A dedicated pathway called the ICL repair pathway repairs interstrand crosslinks.

Interstrand crosslinks, or covalent crosslinks between bases in different DNA strand, can occur during replication or transcription. ICL repair involves the coordination of multiple repair processes, in particular, nucleolytic activity, translesion synthesis (TLS), and HDR. Nucleases are recruited to excise the ICL on either side of the crosslinked bases, while TLS and HDR are coordinated to repair the cut strands. ICL repair can involve the following factors:

endonucleases, e.g., XPF and RAD51C, endonucleases such as RAD51, translesion polymerases, e.g., DNA polymerase zeta and Revl), and the Fanconi anemia (FA) proteins, e.g., FancJ.

Other pathways

Several other DNA repair pathways exist in mammals.

Translesion synthesis (TLS) is a pathway for repairing a single stranded break left after a defective replication event and involves translesion polymerases, e.g., DNA pol and Revl..

Error-free postreplication repair (PRR) is another pathway for repairing a single stranded break left after a defective replication event.

V.5 Targeted Knockdown

Unlike CRISPR/Cas-mediated gene knockout, which permanently eliminates expression by mutating the gene at the DNA level, CRISPR/Cas knockdown allows for temporary reduction of gene expression through the use of artificial transcription factors. Mutating key residues in both DNA cleavage domains of the Cas9 protein (e.g. the DIOA and H840A mutations) results in the generation of a catalytically inactive Cas9 (eiCas9 which is also known as dead Cas9 or dCas9) molecule. A catalytically inactive Cas9 complexes with a gRNA and localizes to the DNA sequence specified by that gRNA's targeting domain, however, it does not cleave the target DNA. Fusion of the dCas9 to an effector domain, e.g., a transcription repression domain, enables recruitment of the effector to any DNA site specified by the gRNA. Although an enzymatically inactive (eiCas9) Cas9 molecule itself can block transcription when recruited to early regions in the coding sequence, more robust repression can be achieved by fusing a transcriptional repression domain (for example KRAB, SID or ERD) to the Cas9 and recruiting it to the target knockdown position, e.g., within lOOObp of sequence 3' of the start codon or within 500 bp of a promoter region 5' of the start codon of a gene. It is likely that targeting DNAsel hypersensitive sites (DHSs) of the promoter may yield more efficient gene repression or activation because these regions are more likely to be accessible to the Cas9 protein and are also more likely to harbor sites for endogenous transcription factors. Especially for gene repression, it is contemplated herein that blocking the binding site of an endogenous transcription factor would aid in downregulating gene expression. In an embodiment, one or more eiCas9 molecules may be used to block binding of one or more endogenous transcription factors. In another embodiment, an eiCas9 molecule can be fused to a chromatin modifying protein. Altering chromatin status can result in decreased expression of the target gene. One or more eiCas9 molecules fused to one or more chromatin modifying proteins may be used to alter chromatin status.

In an embodiment, a gRNA molecule can be targeted to a known transcription response elements (e.g., promoters, enhancers, etc.), a known upstream activating sequences (UAS), and/or sequences of unknown or known function that are suspected of being able to control expression of the target DNA.

CRISPR/Cas-mediated gene knockdown can be used to reduce expression of an unwanted allele or transcript. Contemplated herein are scenarios wherein permanent destruction of the gene is not ideal. In these scenarios, site-specific repression may be used to temporarily reduce or eliminate expression. It is also contemplated herein that the off-target effects of a Cas- repressor may be less severe than those of a Cas-nuclease as a nuclease can cleave any DNA sequence and cause mutations whereas a Cas-repressor may only have an effect if it targets the promoter region of an actively transcribed gene. However, while nuclease-mediated knockout is permanent, repression may only persist as long as the Cas-repressor is present in the cells. Once the repressor is no longer present, it is likely that endogenous transcription factors and gene regulatory elements would restore expression to its natural state.

V.6 Examples of gRNAs in Genome Editing Methods

gRNA molecules as described herein can be used with Cas9 molecules that generate a double strand break or a single strand break to alter the sequence of a target nucleic acid, e.g., a target position or target genetic signature. gRNA molecules useful in these methods are described below.

In an embodiment, the gRNA, e.g., a chimeric gRNA, is configured such that it comprises one or more of the following properties;

a) it can position, e.g., when targeting a Cas9 molecule that makes double strand breaks, a double strand break (i) within 50, 100, 150 or 200 nucleotides of a target position, or (ii) sufficiently close that the target position is within the region of end resection;

b) it has a targeting domain of at least 17 nucleotides, e.g., a targeting domain of (i) 17, (ii) 18, or (iii) 20 nucleotides; and

c)

(i) the proximal and tail domain, when taken together, comprise at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides, e.g., at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides from a naturally occurring S.

pyogenes, S. thermophilus, S. aureus, or N. meningitidis tail and proximal domain, or a sequence that differs by no more than 1, 2, 3, 4, 5; 6, 7, 8, 9 or 10 nucleotides therefrom;

(ii) there are at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides 3' to the last nucleotide of the second complementarity domain, e.g., at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides from the corresponding sequence of a naturally occurring S. pyogenes, S. thermophilus, S. aureus, or N. meningitidis gRNA, or a sequence that differs by no more than 1, 2, 3, 4, 5; 6, 7, 8, 9 or 10 nucleotides therefrom; (iii) there are at least 16, 19, 21, 26, 31, 32, 36, 41, 46, 50, 51, or 54 nucleotides 3' to the last nucleotide of the second complementarity domain that is complementary to its corresponding nucleotide of the first complementarity domain, e.g., at least 16, 19, 21, 26, 31, 32, 36, 41, 46, 50, 51, or 54 nucleotides from the corresponding sequence of a naturally occurring S. pyogenes, S.

thermophilus , S. aureus, or N. meningitidis gRNA, or a sequence that differs by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 nucleotides therefrom;

iv) the tail domain is at least 10, 15, 20, 25, 30, 35 or 40 nucleotides in length, e.g., it comprises at least 10, 15, 20, 25, 30, 35 or 40 nucleotides from a naturally occurring S. pyogenes, S. thermophilus, S. aureus, or N. meningitidis tail domain; or, or a sequence that differs by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 nucleotides therefrom; or

(v) the tail domain comprises 15, 20, 25, 30, 35, 40 nucleotides or all of the corresponding portions of a naturally occurring tail domain, e.g., a naturally occurring S. pyogenes, S. thermophilus, S. aureus, or N. meningitidis tail domain.

In an embodiment, the gRNA is configured such that it comprises properties: a and b(i).

In an embodiment, the gRNA is configured such that it comprises properties: a and b(ii).

In an embodiment, the gRNA is configured such that it comprises properties: a and b(iii).

In an embodiment, the gRNA is configured such that it comprises properties: a and c.

In an embodiment, the gRNA is configured such that in comprises properties: a, b, and c.

In an embodiment, the gRNA is configured such that in comprises properties: a(i), b(i), and c(i).

In an embodiment, the gRNA is configured such that in comprises properties: a(i), b(i), and c(ii).

In an embodiment, the gRNA is configured such that in comprises properties: a(i), b(iii), and c(i).

In an embodiment, the gRNA is configured such that in comprises properties: a(i), b(iii), and c(ii).

In an embodiment, the gRNA, e.g., a chimeric gRNA, is configured such that it comprises one or more of the following properties; a) it can position, e.g., when targeting a Cas9 molecule that makes single strand breaks, a single strand break (i) within 50, 100, 150 or 200 nucleotides of a target position, or (ii) sufficiently close that the target position is within the region of end resection;

b) it has a targeting domain of at least 17 nucleotides, e.g., a targeting domain of (i) 17, (ii) 18, or (iii) 20 nucleotides; and

c)

(i) the proximal and tail domain, when taken together, comprise at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides, e.g., at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides from a naturally occurring S.

pyogenes, S. thermophilus, S. aureus, or N. meningitidis tail and proximal domain, or a sequence that differs by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 nucleotides therefrom;

(ii) there are at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides 3' to the last nucleotide of the second complementarity domain, e.g., at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides from the corresponding sequence of a naturally occurring S. pyogenes, S. thermophilus, S. aureus, or N. meningitidis gRNA, or a sequence that differs by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 nucleotides therefrom;

(iii) there are at least 16, 19, 21, 26, 31, 32, 36, 41, 46, 50, 51, or 54 nucleotides 3' to the last nucleotide of the second complementarity domain that is complementary to its corresponding nucleotide of the first complementarity domain, e.g., at least 16, 19, 21, 26, 31, 32, 36, 41, 46, 50, 51, or 54 nucleotides from the corresponding sequence of a naturally occurring S. pyogenes, S.

thermophilus, S. aureus, or N. meningitidis gRNA, or a sequence that differs by no more than 1, 2, 3, 4, 5; 6, 7, 8, 9 or 10 nucleotides therefrom;

iv) the tail domain is at least 10, 15, 20, 25, 30, 35 or 40 nucleotides in length, e.g., it comprises at least 10, 15, 20, 25, 30, 35 or 40 nucleotides from a naturally occurring S. pyogenes, S. thermophilus, S. aureus, or N. meningitidis tail domain; or, a sequence that differs by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 nucleotides therefrom; or (v) the tail domain comprises 15, 20, 25, 30, 35, 40 nucleotides or all of the corresponding portions of a naturally occurring tail domain, e.g., a naturally occurring S. pyogenes, S. thermophilus, S. aureus, or N. meningitidis tail domain.

In an embodiment, the gRNA is configured such that it comprises properties: a and b(i).

In an embodiment, the gRNA is configured such that it comprises properties: a and b(ii).

In an embodiment, the gRNA is configured such that it comprises properties: a and b(iii).

In an embodiment, the gRNA is configured such that it comprises properties: a and c.

In an embodiment, the gRNA is configured such that in comprises properties: a, b, and c.

In an embodiment, the gRNA is configured such that in comprises properties: a(i), b(i), and c(i).

In an embodiment, the gRNA is configured such that in comprises properties: a(i), b(i), and c(ii).

In an embodiment, the gRNA is configured such that in comprises properties: a(i), b(iii), and c(i).

In an embodiment, the gRNA is configured such that in comprises properties: a(i), b(iii), and c(ii).

In an embodiment, the gRNA is used with a Cas9 nickase molecule having HNH activity, e.g., a Cas9 molecule having the RuvC activity inactivated, e.g., a Cas9 molecule having a mutation at D10, e.g., the D10A mutation.

In an embodiment, the gRNA is used with a Cas9 nickase molecule having RuvC activity, e.g., a Cas9 molecule having the HNH activity inactivated, e.g., a Cas9 molecule having a mutation at H840, e.g., a H840A.

In an embodiment, the gRNAs are used with a Cas9 nickase molecule having RuvC activity, e.g., a Cas9 molecule having the HNH activity inactivated, e.g., a Cas9 molecule having a mutation at N863, e.g., an N863A mutation.

In an embodiment, a pair of gRNAs, e.g., a pair of chimeric gRNAs, comprising a first and a second gRNA, is configured such that they comprises one or more of the following properties;

a) one or both of the gRNAs can position, e.g., when targeting a Cas9 molecule that makes single strand breaks, a single strand break within (i) 50, 100, 150 or 200 nucleotides of a target position, or (ii) sufficiently close that the target position is within the region of end resection;

b) one or both have a targeting domain of at least 17 nucleotides, e.g., a targeting domain of (i) 17 or (ii) 18 nucleotides;

c) for one or both:

(i) the proximal and tail domain, when taken together, comprise at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides, e.g., at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides from a naturally occurring S.

pyogenes, S. thermophilus, S. aureus, or N. meningitidis tail and proximal domain, or a sequence that differs by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 nucleotides therefrom;

(ii) there are at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides 3' to the last nucleotide of the second complementarity domain, e.g., at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides from the corresponding sequence of a naturally occurring S. pyogenes, S. thermophilus, S. aureus, or N. meningitidis gRNA, or a sequence that differs by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 nucleotides therefrom;

(iii) there are at least 16, 19, 21, 26, 31, 32, 36, 41, 46, 50, 51, or 54 nucleotides 3' to the last nucleotide of the second complementarity domain that is complementary to its corresponding nucleotide of the first complementarity domain, e.g., at least 16, 19, 21, 26, 31, 32, 36, 41, 46, 50, 51, or 54 nucleotides from the corresponding sequence of a naturally occurring S. pyogenes, S.

thermophilus, S. aureus, or N. meningitidis gRNA, or a sequence that differs by no more than 1, 2, 3, 4, 5; 6, 7, 8, 9 or 10 nucleotides therefrom;

iv) the tail domain is at least 10, 15, 20, 25, 30, 35 or 40 nucleotides in length, e.g., it comprises at least 10, 15, 20, 25, 30, 35 or 40 nucleotides from a naturally occurring S. pyogenes, S. thermophilus, S. aureus, or N. meningitidis tail domain; or, or a sequence that differs by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 nucleotides therefrom; or (v) the tail domain comprises 15, 20, 25, 30, 35, 40 nucleotides or all of the corresponding portions of a naturally occurring tail domain, e.g., a naturally occurring S. pyogenes, S. thermophilus, S. aureus, or N. meningitidis tail domain; d) the gRNAs are configured such that, when hybridized to target nucleic acid, they are separated by 0-50, 0-100, 0-200, at least 10, at least 20, at least 30 or at least 50 nucleotides; e) the breaks made by the first gRNA and second gRNA are on different strands; and f) the PAMs are facing outwards.

In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a and b(i).

In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a and b(ii).

In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a and b(iii).

In an embodiment, one or both of the gRNAs configured such that it comprises properties: a and c.

In an embodiment, one or both of the gRNAs is configured such that in comprises properties: a, b, and c.

In an embodiment, one or both of the gRNAs is configured such that in comprises properties: a(i), b(i), and c(i).

In an embodiment, one or both of the gRNAs is configured such that in comprises properties: a(i), b(i), and c(ii).

In an embodiment, one or both of the gRNAs is configured such that in comprises properties: a(i), b(i), c, and d.

In an embodiment, one or both of the gRNAs is configured such that in comprises properties: a(i), b(i), c, and e.

In an embodiment, one or both of the gRNAs is configured such that in comprises properties: a(i), b(i), c, d, and e.

In an embodiment, one or both of the gRNAs is configured such that in comprises properties: a(i), b(iii), and c(i).

In an embodiment, one or both of the gRNAs is configured such that in comprises properties: a(i), b(iii), and c(ii). In an embodiment, one or both of the gRNAs is configured such that in comprises properties: a(i), b(iii), c, and d.

In an embodiment, one or both of the gRNAs is configured such that in comprises properties: a(i), b(iii), c, and e.

In an embodiment, one or both of the gRNAs is configured such that in comprises properties: a(i), b(iii), c, d, and e.

In an embodiment, the gRNAs are used with a Cas9 nickase molecule having HNH activity, e.g., a Cas9 molecule having the RuvC activity inactivated, e.g., a Cas9 molecule having a mutation at D 10, e.g., the D10A mutation.

In an embodiment, the gRNAs are used with a Cas9 nickase molecule having RuvC activity, e.g., a Cas9 molecule having the HNH activity inactivated, e.g., a Cas9 molecule having a mutation at H840, e.g., a H840A.

In an embodiment, the gRNAs are used with a Cas9 nickase molecule having RuvC activity, e.g., a Cas9 molecule having the HNH activity inactivated, e.g., a Cas9 molecule having a mutation at N863, e.g., a N863A mutation.

VI. Target Cells

Cas9 molecules, gRNA molecules (e.g., a Cas9 molecule/gRNA molecule complex), and donor nucleic acids can be used to manipulate a cell, e.g., to edit a target nucleic acid, in a wide variety of cells.

In an embodiment, a cell is manipulated by editing (e.g., correcting or introducing a mutation in) the CFTR and/or SCNN1A target genes, e.g., as described herein. In an

embodiment, the expression of the CFTR and/or SCNN1A target genes is modulated, e.g., in vivo. In another embodiment, the expression of the CFTR and/or SCNN1A target genes is modulated, e.g., ex vivo.

The Cas9 and gRNA molecules described herein can be delivered to a target cell.

Methods and compositions discussed herein, provide for treating or delaying the onset or progression of diseases of the lung and airways, including the nose, trachea, bronchus, bronchioles, alveoli, submucosal ducts and submucosal glands. In an embodiment, the target cell is an airway cell, e.g., a nasal epithelial cell, e.g., a tracheal epithelial cell. In an embodiment, the target cell is a lung epithelial cell, e.g., a bronchial epithelial cell, e.g., a proximal bronchial epithelial cell, e.g., a bronchiolar epithelial cell, e.g., an alveolar epithelial cell, e.g., a clara cell, e.g., a ciliated cell, e.g., a goblet cell, e.g., a basal cell, e.g., an acinus cell. Methods and compositions discussed herein, provide for treating or delaying the onset or progression of diseases of the gastrointestinal tract, including pancreas, bile ducts, gallbladder, small intestine, large intestine and salivary glands. In an embodiment, the target cell is a gastrointestinal epithelial cell. In an embodiment, the target cell is a biliary epithelial cell. In an embodiment, the target cell is a pancreatic ductal epithelial cell. In an embodiment, the target cell is a gastrointestinal cell, e.g., an enteroendocrine cell, e.g., a Brunner's gland cell. In an

embodiment, the target cell is a hepatobiliary epithelial cell. In an embodiment, the target cell is a gallbladder epithelial cell. In an embodiment, the target cell is a large intestine epithelial cell. In an embodiment, the target cell is a small intestine epithelial cell. In an embodiment, the target cell is a jejunum epithelial cell. In an embodiment, the target cell is an epithelial cell of the iluem. In an embodiment, the target cell is a duodenum epithelial cell. Methods and

compositions discussed herein, provide for treating or delaying the onset or progression of diseases of the reproductive tract, including the epididymis. In an embodiment, the target cell is a reproductive epithelial cell, e.g. an epididymal epithelial cell. In an embodiment, the target cell is a pulmonary stem cell. In an embodiment, the target cell is a gastrointestinal stem cell.

In an embodiment, the target cell is manipulated ex vivo by editing (e.g., correcting or introducing a mutation in) the CFTR and/or SCNN1A target genes and/or modulating the expression of the CFTR and/or SCNN1A target genes, and administered to the subject. A suitable cell for such manipulation can include a stem cell such as, by way of example, an embryonic stem cell, an induced pluripotent stem cell, a pulmonary stem cell, a gastrointestinal stem cell and a mesenchymal stem cell. In an embodiment, the cell is an induced pluripotent stem cell (iPS) cell or a cell derived from an iPS cell, e.g., an iPS cell generated from the subject, modified to correct or introduce the mutation and differentiated into a clinically relevant cell such as a pulmonary stem cell, a gastrointestinal stem cell, a pulmonary epithelial cell, a bronchial epithelial cell, a proximal bronchial epithelial cell, a bronchiolar epithelial cell, an alveolar epithelial cell, a clara cell, a ciliated cell, a goblet cell, a basal cell, an acinus cell, a gastrointestinal epithelial cell, a biliary epithelial cell, a pancreatic ductal epithelial cell, a hepatobiliary epithelial cell, an enteroendocrine cell, a Brunner' s gland cell, a reproductive epithelial cell, or an epididymal epithelial cell. VII. Delivery, Formulations and Routes of Administration

The components, e.g., a Cas9 molecule and gRNA molecule (e.g., a Cas9

molecule/gRNA molecule complex), and a donor template nucleic acid can be delivered or formulated in a variety of forms, see, e.g., Tables 56-57. In an embodiment, one Cas9 molecule and two or more (e.g., 2, 3, 4, or more) different gRNA molecules are delivered, e.g., by an AAV vector. In an embodiment, the sequence encoding the Cas9 molecule and the sequence(s) encoding the two or more (e.g., 2, 3, 4, or more) different gRNA molecules are present on the same nucleic acid molecule, e.g., an AAV vector. When a Cas9 or gRNA component is encoded as DNA for delivery, the DNA will typically but not necessarily include a control region, e.g., comprising a promoter, to effect expression. Useful promoters for Cas9 molecule sequences include CMV, EFS, EF-la, MSCV, PGK, CAG control promoters. In an embodiment, the promoter is a constitutive promoter. In another embodiment, the promoter is a tissue specific promoter. Useful promoters for gRNAs include HI, 7SK, tRNA and U6 promoters. Promoters with similar or dissimilar strengths can be selected to tune the expression of components.

Sequences encoding a Cas9 molecule can comprise a nuclear localization signal (NLS), e.g., an SV40 NLS. In an embodiment, the sequence encoding a Cas9 molecule comprises at least two nuclear localization signals. In an embodiment a promoter for a Cas9 molecule or a gRNA molecule can be, independently, inducible, tissue specific, or cell specific.

Table 56 provides examples of how the components can be formulated, delivered, or administered.

Table 56

encoded on separate molecules. In this

embodiment, the donor template is provided on the same DNA molecule that encodes the gRNA.

DNA DNA In this embodiment, a Cas9 molecule, typically an eaCas9 molecule, and a gRNA are transcribed from DNA, here from a single molecule. In this embodiment, the donor template is provided as a separate DNA molecule.

DNA 1 DNA 1 DNA In this embodiment, a Cas9 molecule, typically an eaCas9 molecule, and a gRNA are transcribed from DNA. In this embodiment, they are encoded on separate molecules. In this embodiment, the donor template is provided on the same DNA molecule that encodes the Cas9.

DNA RNA DNA In this embodiment, a Cas9 molecule, typically an eaCas9 molecule, is transcribed from DNA, and a gRNA is provided as in vitro transcribed or synthesized RNA. In this embodiment, the donor template is provided as a separate DNA molecule.

DNA RNA DNA In this embodiment, a Cas9 molecule, typically an eaCas9 molecule, is transcribed from DNA, and a gRNA is provided as in vitro transcribed or synthesized RNA. In this embodiment, the donor template is provided on the same DNA molecule that encodes the Cas9.

mRNA RNA DNA In this embodiment, a Cas9 molecule, typically an eaCas9 molecule, is translated from in vitro transcribed mRNA, and a gRNA is provided as in vitro transcribed or synthesized RNA. In this embodiment, the donor template is provided as a DNA molecule.

mRNA DNA DNA In this embodiment, a Cas9 molecule, typically an eaCas9 molecule, is translated from in vitro transcribed mRNA, and a gRNA is transcribed from DNA. In this embodiment, the donor template is provided as a separate DNA molecule.

mRNA Dl ^A In this embodiment, a Cas9 molecule, typically an eaCas9 molecule, is translated from in vitro transcribed mRNA, and a gRNA is transcribed from DNA. In this embodiment, the donor template is provided on the same DNA molecule that encodes the gRNA.

Protein DNA DNA In this embodiment, a Cas9 molecule, typically an eaCas9 molecule, is provided as a protein, and a gRNA is transcribed from DNA. In this

embodiment, the donor template is provided as a separate DNA molecule.

Protein Dl In this embodiment, a Cas9 molecule, typically an eaCas9 molecule, is provided as a protein, and a gRNA is transcribed from DNA. In this embodiment, the donor template is provided on the same DNA molecule that encodes the gRNA.

Protein RNA DNA In this embodiment, an eaCas9 molecule is

provided as a protein, and a gRNA is provided as transcribed or synthesized RNA. In this embodiment, the donor template is provided as a DNA molecule.

Table 57 summarizes various delivery methods for the components of a Cas system, e.g., the Cas9 molecule component and the gRNA molecule component, as described herein.

Table 57

Polymeric YES Transient Depends on Nucleic Acids

Nanoparticles what is and Proteins

delivered

Biological Attenuated YES Transient NO Nucleic Acids

Non-Viral Bacteria

Delivery Engineered YES Transient NO Nucleic Acids

Vehicles Bacteriophages

Mammalian YES Transient NO Nucleic Acids

Virus-like

Particles

Biological YES Transient NO Nucleic Acids liposomes:

Erythrocyte

Ghosts and

Exosomes

DNA-based Delivery of a Cas9 molecule and/or one or more gRNA molecule

Nucleic acids encoding Cas9 molecules (e.g., eaCas9 molecules), gRNA molecules, a donor template nucleic acid, or a combination thereof , can be administered to subjects or delivered into cells by art-known methods or as described herein. For example, Cas9-encoding and/or gRNA-encoding DNA, as well as donor nucleic acids can be delivered, e.g., by vectors (e.g., viral or non-viral vectors), non-vector based methods (e.g., using naked DNA or DNA complexes), or a combination thereof.

DNA encoding Cas9 molecules (e.g., eaCas9 molecules) and/or gRNA molecules, as well as template nucleic acids, can be conjugated to molecules (e.g., N-acetylgalactosamine), thereby promoting uptake by the target cells (e.g., the target cells described herein).

In some embodiments, the Cas9- and/or gRNA-encoding DNA is delivered by a vector (e.g., viral vector/virus or plasmid). In some embodiments the donor nucleic acid is delivered by a vector (e.g., a viral vector/virus or plasmid).

A vector can comprise a sequence that encodes a Cas9 molecule and/or a gRNA molecule. A vector can comprise a donor nucleic acid. A vector can also comprise a sequence encoding a signal peptide {e.g., for nuclear localization, nucleolar localization, mitochondrial localization), fused, e.g., to a Cas9 molecule sequence. For example, ae vector can comprise a nuclear localization sequence (e.g., from SV40) fused to the sequence encoding the Cas9 molecule. One or more regulatory/control elements, e.g., a promoter, an enhancer, an intron, a polyadenylation signal, a Kozak consensus sequence, internal ribosome entry sites (IRES), a 2A sequence, and splice acceptor or donor can be included in the vectors. In some embodiments, the promoter is recognized by RNA polymerase II (e.g., a CMV promoter). In other embodiments, the promoter is recognized by RNA polymerase III (e.g., a U6 promoter). In some embodiments, the promoter is a regulated promoter (e.g., inducible promoter). In other embodiments, the promoter is a constitutive promoter. In some embodiments, the promoter is a tissue specific promoter. In some embodiments, the promoter is a viral promoter. In other embodiments, the promoter is a non-viral promoter.

In some embodiments, the vector or delivery vehicle is a viral vector (e.g., for generation of recombinant viruses). In some embodiments, the virus is a DNA virus (e.g., dsDNA or ssDNA virus). In other embodiments, the virus is an RNA virus (e.g., an ssRNA virus).

Exemplary viral vectors/viruses include, e.g., retroviruses, lentiviruses, adenovirus, adeno- associated virus (AAV), vaccinia viruses, poxviruses, and herpes simplex viruses.

In some embodiments, the virus infects dividing cells. In other embodiments, the virus infects non-dividing cells. In some embodiments, the virus infects both dividing and non- dividing cells. In some embodiments, the virus can integrate into the host genome. In some embodiments, the virus is engineered to have reduced immunity, e.g., in human. In some embodiments, the virus is replication-competent. In other embodiments, the virus is replication- defective, e.g., having one or more coding regions for the genes necessary for additional rounds of virion replication and/or packaging replaced with other genes or deleted. In some

embodiments, the virus causes transient expression of the Cas9 molecule and/or the gRNA molecule. In other embodiments, the virus causes long-lasting, e.g., at least 1 week, 2 weeks, 1 month, 2 months, 3 months, 6 months, 9 months, 1 year, 2 years, or permanent expression, of the Cas9 molecule and/or the gRNA molecule. The packaging capacity of the viruses may vary, e.g., from at least about 4 kb to at least about 30 kb, e.g., at least about 5 kb, 10 kb, 15 kb, 20 kb, 25 kb, 30 kb, 35 kb, 40 kb, 45 kb, or 50 kb.

In an embodiment, the viral vector recognizes a specific cell type or tissue. For example, the viral vector can be pseudotyped with a different/alternative viral envelope glycoprotein; engineered with a cell type-specific receptor (e.g., genetic modification(s) of one or more viral envelope glycoproteins to incorporate a targeting ligand such as a peptide ligand, a single chain antibody, or a growth factor); and/or engineered to have a molecular bridge with dual specificities with one end recognizing a viral glycoprotein and the other end recognizing a moiety of the target cell surface (e.g., a ligand-receptor, monoclonal antibody, avidin-biotin and chemical conjugation).

Exemplary viral vectors/viruses include, e.g., retroviruses, lentiviruses, adenovirus, adeno-associated virus (AAV), vaccinia viruses, poxviruses, and herpes simplex viruses.

In some embodiments, the Cas9- and/or gRNA-encoding sequence is delivered by a recombinant retrovirus. In some embodiments, the donor nucleic acid is delivered by a recombinant retrovirus. In some embodiments, the retrovirus (e.g., Moloney murine leukemia virus) comprises a reverse transcriptase, e.g., that allows integration into the host genome. In some embodiments, the retrovirus is replication-competent. In other embodiments, the retrovirus is replication-defective, e.g., having one of more coding regions for the genes necessary for additional rounds of virion replication and packaging replaced with other genes, or deleted.

In some embodiments, the Cas9- and/or gRNA-encoding sequence is delivered by a recombinant lentivirus. In some embodiments, the donor nucleic acid is delivered by a recombinant lentivirus. For example, the lentivirus is replication-defective, e.g., does not comprise one or more genes required for viral replication.

In some embodiments, the Cas9- and/or gRNA-encoding sequence is delivered by a recombinant adenovirus. In some embodiments, the donor nucleic acid is delivered by a recombinant adenoviru. In some embodiments, the adenovirus is engineered to have reduced immunity in human.

In some embodiments, the Cas9- and/or gRNA-encoding DNA is delivered by a recombinant AAV. In some embodiments, the AAV does not incorporate its genome into that of a host cell, e.g., a target cell as describe herein. In some embodiments, the AAV can incorporate at least part of its genome into that of a host cell, e.g., a target cell as described herein. In some embodiments, the AAV is a self-complementary adeno-associated virus (scAAV), e.g., a scAAV that packages both strands which anneal together to form double stranded DNA. AAV serotypes that may be used in the disclosed methods, include AAV1, AAV2, modified AAV2 (e.g., modifications at Y444F, Y500F, Y730F and/or S662V), AAV3, modified AAV3 (e.g., modifications at Y705F, Y731F and/or T492V), AAV4, AAV5, AAV6, modified AAV6 (e.g., modifications at S663V and/or T492V), AAV8, AAV 8.2, AAV9, AAV rh 10, and pseudotyped AAV, such as AAV2/8, AAV2/5 and AAV2/6 can also be used in the disclosed methods. In an embodiment, an AAV capsid that can be used in the methods described herein is a capsid sequence from serotype AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV.rh8, AAV.rhlO, AAV.rh32/33, AAV.rh43, AAV.rh64Rl, or AAV7m8.

In an embodiment, the Cas9- and/or gRNA-encoding DNA is delivered in a re- engineered AAV capsid, e.g., with 50% or greater, e.g., 60% or greater, 70% or greater, 80% or greater, 90% or greater, or 95% or greater, sequence homology with a capsid sequence from serotypes AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV.rh8, AAV.rhl0, AAV.rh32/33, AAV.rh43, or AAV.rh64Rl.

In an embodiment, the Cas9- and/or gRNA-encoding DNA is delivered by a chimeric AAV capsid. In an embodiment, the donor nucleic acid is delivered by a chimeric AAV capsid. Exemplary chimeric AAV capsids include, but are not limited to, AAV9il, AAV2i8, AAV-DJ, AAV2G9, AAV2i8G9, or AAV8G9.

In an embodiment, the AAV is a self-complementary adeno-associated virus (scAAV), e.g., a scAAV that packages both strands which anneal together to form double stranded DNA.

In some embodiments, the Cas9- and/or gRNA-encoding DNA is delivered by a hybrid virus, e.g., a hybrid of one or more of the viruses described herein. In an embodiment, the hybrid virus is hybrid of an AAV (e.g., of any AAV serotype), with a Bocavirus, B19 virus, porcine AAV, goose AAV, feline AAV, canine AAV, or MVM.

A Packaging cell is used to form a virus particle that is capable of infecting a target cell. Such a cell includes a 293 cell, which can package adenovirus, and a ψ2 cell or a PA317 cell, which can package retrovirus. A viral vector used in gene therapy is usually generated by a producer cell line that packages a nucleic acid vector into a viral particle. The vector typically contains the minimal viral sequences required for packaging and subsequent integration into a host or target cell (if applicable), with other viral sequences being replaced by an expression cassette encoding the protein to be expressed, eg. Cas9. For example, an AAV vector used in gene therapy typically only possesses inverted terminal repeat (ITR) sequences from the AAV genome which are required for packaging and gene expression in the host or target cell. The missing viral functions can be supplied in trans by the packaging cell line and/or plasmid containing E2A, E4, and VA genes from adenovirus, and plasmid encoding Rep and Cap genes from AAV, as described in "Triple Transfection Protocol." Henceforth, the viral DNA is packaged in a cell line, which contains a helper plasmid encoding the other AAV genes, namely rep and cap, but lacking ITR sequences. In embodiment, the viral DNA is packaged in a producer cell line, which contains El A and/or E1B genes from adenovirus. The cell line is also infected with adenovirus as a helper. The helper virus (e.g., adenovirus or HSV) or helper plasmid promotes replication of the AAV vector and expression of AAV genes from the helper plasmid with ITRs. The helper plasmid is not packaged in significant amounts due to a lack of ITR sequences. Contamination with adenovirus can be reduced by, e.g., heat treatment to which adenovirus is more sensitive than AAV.

In an embodiment, the viral vector has the ability of cell type and/or tissue type recognition. For example, the viral vector can be pseudotyped with a different/alternative viral envelope glycoprotein; engineered with a cell type-specific receptor (e.g., geneticmodification of the viral envelope glycoproteins to incorporate targeting ligands such as a peptide ligand, a single chain antibodie, a growth factor); and/or engineered to have a molecular bridge with dual specificities with one end recognizing a viral glycoprotein and the other end recognizing a moiety of the target cell surface (e.g., ligand-receptor, monoclonal antibody, avidin-biotin and chemical conjugation).

In an embodiment, the viral vector achieves cell type specific expression. For example, a tissue-specific promoter can be constructed to restrict expression of the transgene (Cas 9 and gRNA) in only the target cell. The specificity of the vector can also be mediated by microRNA- dependent control of transgene expression. In an embodiment, the viral vector has increased efficiency of fusion of the viral vector and a target cell membrane. For example, a fusion protein such as fusion-competent hemagglutin (HA) can be incorporated to increase viral uptake into cells. In an embodiment, the viral vector has the ability of nuclear localization. For example, aviruse that requires the breakdown of the nuclear envelope (during cell division) and therefore will not infect a non-diving cell can be altered to incorporate a nuclear localization peptide in the matrix protein of the virus thereby enabling the transduction of non-proliferating cells.

In some embodiments, the Cas9- and/or gRNA-encoding DNA is delivered by a non- vector based method (e.g., using naked DNA or DNA complexes). For example, the DNA can be delivered, e.g., by organically modified silica or silicate (Ormosil), electroporation, transient cell compression or squeezing (e.g., as described in Lee, et al [2012] Nano Lett 12: 6322-27), gene gun, sonoporation, magnetofection, lipid-mediated transfection, dendrimers, inorganic nanoparticles, calcium phosphates, or a combination thereof.

In an embodiment, delivery via electroporation comprises mixing the cells with the Cas9- and/or gRNA-encoding DNA in a cartridge, chamber or cuvette and applying one or more electrical impulses of defined duration and amplitude. In an embodiment, delivery via electroporation is performed using a system in which cells are mixed with the Cas9-and/or gRNA-encoding DNA in a vessel connected to a device (eg, a pump) which feeds the mixture into a cartridge, chamber or cuvette wherein one or more electrical impulses of defined duration and amplitude are applied, after which the cells are delivered to a second vessel.

In some embodiments, the Cas9- and/or gRNA-encoding DNA is delivered by a combination of a vector and a non-vector based method. In some embodiments, the donor nucleic acid is delivered by a combination of a vector and a non-vector based method. For example, a virosome comprises a liposome combined with an inactivated virus (e.g., HIV or influenza virus), which can result in more efficient gene transfer, e.g., in a respiratory epithelial cell than either a viral or a liposomal method alone.

In an embodiment, the delivery vehicle is a non- viral vector. In an embodiment, the non- viral vector is an inorganic nanoparticle. Exemplary inorganic nanoparticles include, e.g., magnetic nanoparticles (e.g., FesMnOi) or silica. The outer surface of the nanoparticle can be conjugated with a positively charged polymer (e.g., polyethylenimine, polylysine, polyserine) which allows for attachment (e.g., conjugation or entrapment) of payload. In an embodiment, the non-viral vector is an organic nanoparticle. Exemplary organic nanoparticles include, e.g., SNALP liposomes (e.g., SNALP liposomes that contain cationic lipids together with neutral helper lipids and polyethylene glycol (PEG)-conjugated lipids) and protamine-nucleic acid complexes, e.g., protamine-nucleic acid complexes coated with lipid coating.

Exemplary lipids for gene transfer are shown below in Table 58.

Table 58: Lipids Used for Gene Transfer

Dioctadecylamidoglycylspermine DOGS Cationic

N- (3- Aminopropyl) -N,N-dimethyl-2,3-bis(dodecyloxy) - 1 - GAP-DLRIE Cationic propanaminium bromide

Cetyltrimethylammonium bromide CTAB Cationic

6-Lauroxyhexyl ornithinate LHON Cationic l-(2,3-Dioleoyloxypropyl)-2,4,6-trimethylpyridinium 2Oc Cationic

2,3-Dioleyloxy-N-[2(sperminecarboxamido-ethyl]-N,N- DOSPA Cationic dimethyl-l-propanaminium trifluoroacetate

l,2-Dioleyl-3-trimethylammonium-propane DOPA Cationic

N-(2-Hydroxyethyl)-N,N-dimethyl-2,3-bis(tetradecyloxy)-l- MDRIE Cationic propanaminium bromide

Dimyristooxypropyl dimethyl hydroxyethyl ammonium DMRI Cationic bromide

3P-[N-(N',N'-Dimethylaminoethane)-carbamoyl]cholesterol DC-Choi Cationic

Bis-guanidium-tren-cholesterol BGTC Cationic l,3-Diodeoxy-2-(6-carboxy-spermyl)-propylamide DOSPER Cationic

Dimethyloctadecylammonium bromide DDAB Cationic

Dioctadecylamidoglicylspermidin DSL Cationic rac-[(2,3-Dioctadecyloxypropyl)(2-hydroxyethyl)]- CLIP-1 Cationic dimethylammonium chloride

rac-[2(2,3-Dihexadecyloxypropyl- CLIP-6 Cationic oxymethyloxy)ethyl]trimethylammonium bromide

Ethyldimyristoylphosphatidylcholine EDMPC Cationic l,2-Distearyloxy-N,N-dimethyl-3-aminopropane DSDMA Cationic

1,2-Dimyristoyl-trimethylammonium propane DMTAP Cationic

Ο,Ο'-Dimyristyl-N-lysyl aspartate DMKE Cationic l,2-Distearoyl-sn-glycero-3-ethylphosphocholine DSEPC Cationic

N-Palmitoyl D-erythro-sphingosyl carbamoyl-spermine CCS Cationic

N-t-Butyl-N0-tetradecyl-3-tetradecylaminopropionamidine diC14-amidine Cationic

Octadecenolyoxy[ethyl-2-heptadecenyl-3 hydroxyethyl] DOTIM Cationic imidazolinium chloride

Nl-Cholesteryloxycarbonyl-3,7-diazanonane-l,9-diamine CDAN Cationic

2-(3-[Bis(3-amino-propyl)-amino]propylamino)-N- RPR209120 Cationic ditetradecylcarbamoylme-ethyl-acetamide

l,2-dilinoleyloxy-3- dimethylaminopropane DLinDMA Cationic

2,2-dilinoleyl-4-dimethylaminoethyl- [ 1 ,3] - dioxolane DLin-KC2- Cationic

DMA

dilinoleyl- methyl-4-dimethylaminobutyrate DLin-MC3- Cationic

DMA

Exemplary polymers for gene transfer are shown below in Table 59.

Table 59: Polymers Used for Gene Transfer

Polyethylenimine PEI

Dithiobis(succinimidylpropionate) DSP

Dimethyl-3,3'-dithiobispropionimidate DTBP

Poly(ethylene imine) biscarbamate PEIC

Poly(L-lysine) PLL

Histidine modified PLL

Poly(N-vinylpyrrolidone) PVP

Poly(propylenimine) PPI

Poly(amidoamine) PAMAM

Poly(amido ethylenimine) SS-PAEI

Triethylenetetramine TETA

Poly ( β- aminoester)

Poly(4-hydroxy-L-proline ester) PHP

Poly(allylamine)

Poly(a-[4-aminobutyl]-L-glycolic acid) PAGA

Poly(D,L-lactic-co-glycolic acid) PLGA

Poly(N-ethyl-4-vinylpyridinium bromide)

Poly (pho sphazene) s PPZ

Poly (pho sphoester) s PPE

Poly (pho sphoramidate) s PPA

Poly(N-2-hydroxypropylmethacrylamide) pHPMA

Poly (2-(dimethylamino)ethyl methacrylate) pDMAEMA

Poly(2-aminoethyl propylene phosphate) PPE-EA

Chitosan

Galactosylated chitosan

N-Dodacylated chitosan

Histone

Collagen

Dextran- spermine D-SPM

In an embodiment, the vehicle has targeting modifications to increase target cell update of nanoparticles and liposomes, e.g., cell specific antigens, monoclonal antibodies, single chain antibodies, aptamers, polymers, sugars, and cell penetrating peptides. In an embodiment, the vehicle uses fusogenic and endosome-destabilizing peptides/polymers. In an embodiment, the vehicle undergoes acid-triggered conformational changes (e.g., to accelerate endosomal escape of the cargo). In an embodiment, a stimuli-cleavable polymer is used, e.g., for release in a cellular compartment. For example, disulfide-based cationic polymers that are cleaved in the reducing cellular environment can be used.

In an embodiment, the delivery vehicle is a biological non-viral delivery vehicle. In an embodiment, the vehicle is an attenuated bacterium (e.g., naturally or artificially engineered to be invasive but attenuated to prevent pathogenesis and expressing the transgene (e.g., Listeria monocytogenes, certain Salmonella strains, Bifidobacterium longum, and modified Escherichia coli), bacteria having nutritional and tissue-specific tropism to target specific tissues, bacteria having modified surface proteins to alter target tissue specificity). In an embodiment, the vehicle is a genetically modified bacteriophage (e.g., engineered phages having large packaging capacity, less immunogenic, containing mammalian plasmid maintenance sequences and having incorporated targeting ligands). In an embodiment, the vehicle is a mammalian virus-like particle. For example, modified viral particles can be generated (e.g., by purification of the "empty" particles followed by ex vivo assembly of the virus with the desired cargo). The vehicle can also be engineered to incorporate targeting ligands to alter target tissue specificity. In an embodiment, the vehicle is a biological liposome. For example, the biological liposome is a phospholipid-based particle derived from human cells (e.g., erythrocyte ghosts, which are red blood cells broken down into spherical structures derived from the subject (e.g., tissue targeting can be achieved by attachment of various tissue or cell-specific ligands), or secretory exosomes - subject (i.e., patient) derived membrane-bound nanovescicle (30 -100 nm) of endocytic origin (e.g., can be produced from various cell types and can therefore be taken up by cells without the need of for targeting ligands).

In an embodiment, the delivery vehicle is a powder comprising, e.g., calcium carbonate, sucrose, mannitol, dextrose, or lactose.

In an embodiment, components are delivered as an aerosol.

In an embodiment, one or more nucleic acid molecules (e.g., DNA molecules) other than the components of a Cas system, e.g., the Cas9 molecule component and/or the gRNA molecule component described herein, are delivered. In an embodiment, the nucleic acid molecule is delivered at the same time as one or more of the components of the Cas system are delivered. In an embodiment, the nucleic acid molecule is delivered before or after (e.g., less than about 30 minutes, 1 hour, 2 hours, 3 hours, 6 hours, 9 hours, 12 hours, 1 day, 2 days, 3 days, 1 week, 2 weeks, or 4 weeks) one or more of the components of the Cas system are delivered. In an embodiment, the nucleic acid molecule is delivered by a different means than one or more of the components of the Cas system, e.g., the Cas9 molecule component and/or the gRNA molecule component, are delivered. The nucleic acid molecule can be delivered by any of the delivery methods described herein. For example, the nucleic acid molecule can be delivered by a viral vector, e.g., an integration-deficient lentivirus, and the Cas9 molecule component and/or the gRNA molecule component can be delivered by electroporation, e.g., such that the toxicity caused by nucleic acids (e.g., DNAs) can be reduced. In an embodiment, the nucleic acid molecule encodes a therapeutic protein, e.g., a protein described herein. In an embodiment, the nucleic acid molecule encodes an RNA molecule, e.g., an RNA molecule described herein.

Delivery of RNA encoding a Cas9 molecule

RNA encoding Cas9 molecules (e.g., eaCas9 molecules or eiCas9 molecules) and/or gRNA molecules, can be delivered into cells, e.g., target cells described herein, by art-known methods or as described herein. For example, Cas9-encoding and/or gRNA-encoding RNA can be delivered, e.g., by microinjection, electroporation, transient cell compression or squeezing (e.g., as described in Lee, et al [2012] Nano Lett 12: 6322-27), lipid-mediated transfection, lipid- mediated transfection, peptide-mediated delivery, or a combination thereof. Cas9-encoding and/or gRNA-encoding RNA can be conjugated to molecules promoting uptake by the target cells (e.g., target cells described herein).

In an embodiment, delivery via electroporation comprises mixing the cells with the RNA encoding Cas9 molecules (e.g., eaCas9 molecules, eiCas9 molecules or eiCas9 fusion protiens) and/or gRNA molecules, with or without donor nucleic acid molecules in a cartridge, chamber or cuvette and applying one or more electrical impulses of defined duration and amplitude. In an embodiment, delivery via electroporation is performed using a system in which cells are mixed with the RNA encoding Cas9 molecules (e.g., eaCas9 molecules, eiCas9 molecules or eiCas9 fusion protiens) and/or gRNA molecules, with or without donor nucleic acid molecules in a vessel connected to a device (eg, a pump) which feeds the mixture into a cartridge, chamber or cuvette wherein one or more electrical impulses of defined duration and amplitude are applied, after which the cells are delivered to a second vessel.

Delivery Cas9 molecule protein

Cas9 molecules (e.g., eaCas9 molecules or eiCas9 molecules) can be delivered into cells by art-known methods or as described herein. For example, Cas9 protein molecules can be delivered, e.g., by microinjection, electroporation, lipid-mediated transfection, peptide-mediated delivery, or a combination thereof. Delivery can be accompanied by DNA encoding a gRNA or by a gRNA. Cas9 protein can be conjugated to molecules promoting uptake by the target cells (e.g., target cells described herein).

In an embodiment, delivery via electroporation comprises mixing the cells with the Cas9 molecules (e.g., eaCas9 molecules, eiCas9 molecules or eiCas9 fusion protiens) and/or gRNA molecules, with or without donor nucleic acid, in a cartridge, chamber or cuvette and applying one or more electrical impulses of defined duration and amplitude. In an embodiment, delivery via electroporation is performed using a system in which cells are mixed with the Cas9 molecules (e.g., eaCas9 molecules, eiCas9 molecules or eiCas9 fusion protiens) and/or gRNA molecules, with or without donor nucleic acid in a vessel connected to a device (eg, a pump) which feeds the mixture into a cartridge, chamber or cuvette wherein one or more electrical impulses of defined duration and amplitude are applied, after which the cells are delivered to a second vessel.

Route of Administration

Systemic modes of administration include oral and parenteral routes. Parenteral routes include, by way of example, intravenous, intra-arterial, intraosseous, intramuscular, intradermal, subcutaneous and intraperitoneal routes. Components administered systemically may be modified or formulated to target the components to specific cells, e.g., airway epithelial cells, pulmonary epithelial cells, gastrointestinal epithelial cells, biliary epithelial cells, pancreatic ductal epithelial cells, reproductive epithelial cells or pulmonary stem cells.

Local modes of administration include, by way of example, inhalation, intra-nasal instillation, and intraparenchymal injection, e.g., intraparenchymal injection into the lung, bronchial tree, liver, pancreas, pancreatic duct, bile duct, gastrointestinal tract or reproductive tract. In an embodiment, significantly smaller amounts of the components (compared with systemic approaches) may exert an effect when administered locally (for example, by inhalation) compared to when administered systemically (for example, intravenously). Local modes of administration can reduce or eliminate the incidence of potentially toxic side effects that may occur when therapeutically effective amounts of a component are administered systemically.

In an embodiment, components described herein are delivered by inhalation.

In an embodiment, nanoparticle or viral, e.g., AAV vector, delivery is via inhalation. In an embodiment, subjects are treated with mucus loosening agents and/or chest physical therapy prior to administration of components by inhalation.

Administration may be provided as a periodic bolus or as continuous infusion from an internal reservoir or from an external reservoir (for example, from an intravenous bag).

Components may be administered locally, for example, by continuous release from a sustained release drug delivery device.

In addition, components may be formulated to permit release over a prolonged period of time. A release system can include a matrix of a biodegradable material or a material which releases the incorporated components by diffusion. The components can be homogeneously or heterogeneously distributed within the release system. A variety of release systems may be useful, however, the choice of the appropriate system will depend upon rate of release required by a particular application. Both non-degradable and degradable release systems can be used. Suitable release systems include polymers and polymeric matrices, non-polymeric matrices, or inorganic and organic excipients and diluents such as, but not limited to, calcium carbonate and sugar (for example, trehalose). Release systems may be natural or synthetic. However, synthetic release systems are preferred because generally they are more reliable, more reproducible and produce more defined release profiles. The release system material can be selected so that components having different molecular weights are released by diffusion through or degradation of the material.

Representative synthetic, biodegradable polymers include, for example: polyamides such as poly(amino acids) and poly(peptides); polyesters such as poly(lactic acid), poly(glycolic acid), poly(lactic-co-glycolic acid), and poly(caprolactone); poly(anhydrides); polyorthoesters;

polycarbonates; and chemical derivatives thereof (substitutions, additions of chemical groups, for example, alkyl, alkylene, hydroxylations, oxidations, and other modifications routinely made by those skilled in the art), copolymers and mixtures thereof. Representative synthetic, non- degradable polymers include, for example: polyethers such as poly(ethylene oxide),

poly(ethylene glycol), and poly(tetramethylene oxide); vinyl polymers-polyacrylates and polymethacrylates such as methyl, ethyl, other alkyl, hydroxyethyl methacrylate, acrylic and methacrylic acids, and others such as poly(vinyl alcohol), poly(vinyl pyrolidone), and poly(vinyl acetate); poly(urethanes); cellulose and its derivatives such as alkyl, hydroxyalkyl, ethers, esters, nitrocellulose, and various cellulose acetates; polysiloxanes; and any chemical derivatives thereof (substitutions, additions of chemical groups, for example, alkyl, alkylene, hydroxylations, oxidations, and other modifications routinely made by those skilled in the art), copolymers and mixtures thereof.

Poly(lactide-co-glycolide) microsphere can also be used for injection. Typically the microspheres are composed of a polymer of lactic acid and glycolic acid, which are structured to form hollow spheres. The spheres can be approximately 15-30 microns in diameter and can be loaded with components described herein.

Bi-Modal or Differential Delivery of Components

Separate delivery of the components of a Cas system, e.g., the Cas9 molecule component and the gRNA molecule component, and more particularly, delivery of the components by differing modes, can enhance performance, e.g., by improving tissue specificity and safety.

In an embodiment, the Cas9 molecule and the gRNA molecule are delivered by different modes, or as sometimes referred to herein as differential modes. Different or differential modes, as used herein, refer modes of delivery that confer different pharmacodynamic or

pharmacokinetic properties on the subject component molecule, e.g., a Cas9 molecule, gRNA molecule, or template nucleic acid. For example, the modes of delivery can result in different tissue distribution, different half-life, or different temporal distribution, e.g., in a selected compartment, tissue, or organ.

Some modes of delivery, e.g., delivery by a nucleic acid vector that persists in a cell, or in progeny of a cell, e.g., by autonomous replication or insertion into cellular nucleic acid, result in more persistent expression of and presence of a component. Examples include viral, e.g., adeno- associated virus or lentivirus, delivery.

By way of example, the components, e.g., a Cas9 molecule and a gRNA molecule, can be delivered by modes that differ in terms of resulting half-life or persistent of the delivered component the body, or in a particular compartment, tissue or organ. In an embodiment, a gRNA molecule can be delivered by such modes. The Cas9 molecule component can be delivered by a mode which results in less persistence or less exposure to the body or a particular compartment or tissue or organ.

More generally, in an embodiment, a first mode of delivery is used to deliver a first component and a second mode of delivery is used to deliver a second component. The first mode of delivery confers a first pharmacodynamic or pharmacokinetic property. The first pharmacodynamic property can be, e.g., distribution, persistence, or exposure, of the component, or of a nucleic acid that encodes the component, in the body, a compartment, tissue or organ. The second mode of delivery confers a second pharmacodynamic or pharmacokinetic property. The second pharmacodynamic property can be, e.g., distribution, persistence, or exposure, of the component, or of a nucleic acid that encodes the component, in the body, a compartment, tissue or organ.

In an embodiment, the first pharmacodynamic or pharmacokinetic property, e.g., distribution, persistence or exposure, is more limited than the second pharmacodynamic or pharmacokinetic property.

In an embodiment, the first mode of delivery is selected to optimize, e.g., minimize, a pharmacodynamic or pharmacokinetic property, e.g., distribution, persistence or exposure.

In an embodiment, the second mode of delivery is selected to optimize, e.g., maximize, a pharmacodynamic or pharmcokinetic property, e.g., distribution, persistence or exposure.

In an embodiment, the first mode of delivery comprises the use of a relatively persistent element, e.g., a nucleic acid, e.g., a plasmid or viral vector, e.g., an AAV or lentivirus. As such vectors are relatively persistent product transcribed from them would be relatively persistent.

In an embodiment, the second mode of delivery comprises a relatively transient element, e.g., an RNA or protein.

In an embodiment, the first component comprises gRNA, and the delivery mode is relatively persistent, e.g., the gRNA is transcribed from a plasmid or viral vector, e.g., an AAV or lentivirus. Transcription of these genes would be of little physiological consequence because the genes do not encode for a protein product, and the gRNAs are incapable of acting in isolation. The second component, a Cas9 molecule, is delivered in a transient manner, for example as mRNA or as protein, ensuring that the full Cas9 molecule/gRNA molecule complex is only present and active for a short period of time.

Furthermore, the components can be delivered in different molecular form or with different delivery vectors that complement one another to enhance safety and tissue specificity.

Use of differential delivery modes can enhance performance, safety and efficacy. E.g., the likelihood of an eventual off-target modification can be reduced. Delivery of immunogenic components, e.g., Cas9 molecules, by less persistent modes can reduce immunogenicity, as peptides from the bacterially-derived Cas enzyme are displayed on the surface of the cell by MHC molecules. A two-part delivery system can alleviate these drawbacks.

Differential delivery modes can be used to deliver components to different, but overlapping target regions. The formation active complex is minimized outside the overlap of the target regions. Thus, in an embodiment, a first component, e.g., a gRNA molecule is delivered by a first delivery mode that results in a first spatial, e.g., tissue, distribution. A second component, e.g., a Cas9 molecule is delivered by a second delivery mode that results in a second spatial, e.g., tissue, distribution. In an embodiment, the first mode comprises a first element selected from a liposome, nanoparticle, e.g., polymeric nanoparticle, and a nucleic acid, e.g., viral vector. The second mode comprises a second element selected from the group. In an embodiment, the first mode of delivery comprises a first targeting element, e.g., a cell specific receptor or an antibody, and the second mode of delivery does not include that element. In embodiment, the second mode of delivery comprises a second targeting element, e.g., a second cell specific receptor or second antibody.

When the Cas9 molecule is delivered in a virus delivery vector, a liposome, or polymeric nanoparticle, there is the potential for delivery to and therapeutic activity in multiple tissues, when it may be desirable to only target a single tissue. A two-part delivery system can resolve this challenge and enhance tissue specificity. If the gRNA molecule and the Cas9 molecule are packaged in separated delivery vehicles with distinct but overlapping tissue tropism, the fully functional complex is only be formed in the tissue that is targeted by both vectors.

Ex vivo delivery

In some embodiments, components described in Table 56 are introduced into cells which are then introduced into the subject e.g., cells are removed from a subject, manipulated ex vivo and then introduced into the subject. Methods of introducing the components can include, e.g., any of the delivery methods described herein, e.g., any of the delivery methods described in Table 57.

VIII. Modified Nucleosides, Nucleotides, and Nucleic Acids

Modified nucleosides and modified nucleotides can be present in nucleic acids, e.g., particularly gRNA, but also other forms of RNA, e.g., mRNA, RNAi, or siRNA. As described herein, "nucleoside" is defined as a compound containing a five-carbon sugar molecule (a pentose or ribose) or derivative thereof, and an organic base, purine or pyrimidine, or a derivative thereof. As described herein, "nucleotide" is defined as a nucleoside further comprising a phosphate group.

Modified nucleosides and nucleotides can include one or more of:

(i) alteration, e.g., replacement, of one or both of the non-linking phosphate oxygens and/or of one or more of the linking phosphate oxygens in the phosphodiester backbone linkage;

(ii) alteration, e.g., replacement, of a constituent of the ribose sugar, e.g., of the 2' hydroxyl on the ribose sugar;

(iii) wholesale replacement of the phosphate moiety with "dephospho" linkers;

(iv) modification or replacement of a naturally occurring nucleobase;

(v) replacement or modification of the ribose-phosphate backbone;

(vi) modification of the 3' end or 5' end of the oligonucleotide, e.g., removal,

modification or replacement of a terminal phosphate group or conjugation of a moiety; and

(vii) modification of the sugar.

The modifications listed above can be combined to provide modified nucleosides and nucleotides that can have two, three, four, or more modifications. For example, a modified nucleoside or nucleotide can have a modified sugar and a modified nucleobase. In an

embodiment, every base of a gRNA is modified, e.g., all bases have a modified phosphate group, e.g., all are phosphorothioate groups. In an embodiment, all, or substantially all, of the phosphate groups of a unimolecular or modular gRNA molecule are replaced with

phosphorothioate groups.

In an embodiment, modified nucleotides, e.g., nucleotides having modifications as described herein, can be incorporated into a nucleic acid, e.g., a "modified nucleic acid." In some embodiments, the modified nucleic acids comprise one, two, three or more modified nucleotides. In some embodiments, at least 5% (e.g., at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, or about 100%) of the positions in a modified nucleic acid are a modified nucleotides. Unmodified nucleic acids can be prone to degradation by, e.g., cellular nucleases. For example, nucleases can hydrolyze nucleic acid phosphodiester bonds. Accordingly, in one aspect the modified nucleic acids described herein can contain one or more modified nucleosides or nucleotides, e.g., to introduce stability toward nucleases.

In some embodiments, the modified nucleosides, modified nucleotides, and modified nucleic acids described herein can exhibit a reduced innate immune response when introduced into a population of cells, both in vivo and ex vivo. The term "innate immune response" includes a cellular response to exogenous nucleic acids, including single stranded nucleic acids, generally of viral or bacterial origin, which involves the induction of cytokine expression and release, particularly the interferons, and cell death. In some embodiments, the modified nucleosides, modified nucleotides, and modified nucleic acids described herein can disrupt binding of a major groove interacting partner with the nucleic acid. In some embodiments, the modified

nucleosides, modified nucleotides, and modified nucleic acids described herein can exhibit a reduced innate immune response when introduced into a population of cells, both in vivo and ex vivo, and also disrupt binding of a major groove interacting partner with the nucleic acid.

Definitions of Chemical Groups

As used herein, "alkyl" is meant to refer to a saturated hydrocarbon group which is straight-chained or branched. Example alkyl groups include methyl (Me), ethyl (Et), propyl (e.g., n-propyl and isopropyl), butyl (e.g., n-butyl, isobutyl, t-butyl), pentyl (e.g., n-pentyl, isopentyl, neopentyl), and the like. An alkyl group can contain from 1 to about 20, from 2 to about 20, from 1 to about 12, from 1 to about 8, from 1 to about 6, from 1 to about 4, or from 1 to about 3 carbon atoms.

As used herein, "aryl" refers to monocyclic or polycyclic (e.g., having 2, 3 or 4 fused rings) aromatic hydrocarbons such as, for example, phenyl, naphthyl, anthracenyl,

phenanthrenyl, indanyl, indenyl, and the like. In some embodiments, aryl groups have from 6 to about 20 carbon atoms.

As used herein, "alkenyl" refers to an aliphatic group containing at least one double bond.

As used herein, "alkynyl" refers to a straight or branched hydrocarbon chain containing 2-12 carbon atoms and characterized in having one or more triple bonds. Examples of alkynyl groups include, but are not limited to, ethynyl, propargyl, and 3-hexynyl. As used herein, "arylalkyl" or "aralkyl" refers to an alkyl moiety in which an alkyl hydrogen atom is replaced by an aryl group. Aralkyl includes groups in which more than one hydrogen atom has been replaced by an aryl group. Examples of "arylalkyl" or "aralkyl" include benzyl, 2-phenylethyl, 3-phenylpropyl, 9-fluorenyl, benzhydryl, and trityl groups.

As used herein, "cycloalkyl" refers to a cyclic, bicyclic, tricyclic, or polycyclic non- aromatic hydrocarbon groups having 3 to 12 carbons. Examples of cycloalkyl moieties include, but are not limited to, cyclopropyl, cyclopentyl, and cyclohexyl.

As used herein, "heterocyclyl" refers to a monovalent radical of a heterocyclic ring system. Representative heterocyclyls include, without limitation, tetrahydrofuranyl,

tetrahydrothienyl, pyrrolidinyl, pyrrolidonyl, piperidinyl, pyrrolinyl, piperazinyl, dioxanyl, dioxolanyl, diazepinyl, oxazepinyl, thiazepinyl, and morpholinyl.

As used herein, "heteroaryl" refers to a monovalent radical of a heteroaromatic ring system. Examples of heteroaryl moieties include, but are not limited to, imidazolyl, oxazolyl, thiazolyl, triazolyl, pyrrolyl, furanyl, indolyl, thiophenyl pyrazolyl, pyridinyl, pyrazinyl, pyridazinyl, pyrimidinyl, indolizinyl, purinyl, naphthyridinyl, quinolyl, and pteridinyl.

Phosphate Backbone Modifications

The Phosphate Group

In some embodiments, the phosphate group of a modified nucleotide can be modified by replacing one or more of the oxygens with a different substituent. Further, the modified nucleotide, e.g., modified nucleotide present in a modified nucleic acid, can include the wholesale replacement of an unmodified phosphate moiety with a modified phosphate as described herein. In some embodiments, the modification of the phosphate backbone can include alterations that result in either an uncharged linker or a charged linker with

unsymmetrical charge distribution.

Examples of modified phosphate groups include, phosphorothioate, phosphoroselenates, borano phosphates, borano phosphate esters, hydrogen phosphonates, phosphoroamidates, alkyl or aryl phosphonates and phosphotriesters. In some embodiments, one of the non-bridging phosphate oxygen atoms in the phosphate backbone moiety can be replaced by any of the following groups: sulfur (S), selenium (Se), BR₃ (wherein R can be, e.g., hydrogen, alkyl, or aryl), C (e.g., an alkyl group, an aryl group, and the like), H, NR₂ (wherein R can be, e.g., hydrogen, alkyl, or aryl), or OR (wherein R can be, e.g., alkyl or aryl). The phosphorous atom in an unmodified phosphate group is achiral. However, replacement of one of the non-bridging oxygens with one of the above atoms or groups of atoms can render the phosphorous atom chiral; that is to say that a phosphorous atom in a phosphate group modified in this way is a stereogenic center. The stereogenic phosphorous atom can possess either the "R" configuration (herein Rp) or the "S" configuration (herein Sp).

Phosphorodithioates have both non-bridging oxygens replaced by sulfur. The phosphorus center in the phosphorodithioates is achiral which precludes the formation of oligoribonucleotide diastereomers. In some embodiments, modifications to one or both non-bridging oxygens can also include the replacement of the non-bridging oxygens with a group independently selected from S, Se, B, C, H, N, and OR (R can be, e.g., alkyl or aryl).

The phosphate linker can also be modified by replacement of a bridging oxygen, (i.e., the oxygen that links the phosphate to the nucleoside), with nitrogen (bridged phosphoroamidates), sulfur (bridged phosphorothioates) and carbon (bridged methylenephosphonates). The replacement can occur at either linking oxygen or at both of the linking oxygens.

Replacement of the Phosphate Group

The phosphate group can be replaced by non-phosphorus containing connectors. In some embodiments, the charge phosphate group can be replaced by a neutral moiety.

Examples of moieties which can replace the phosphate group can include, without limitation, e.g., methyl phosphonate, hydroxylamino, siloxane, carbonate, carboxymethyl, carbamate, amide, thioether, ethylene oxide linker, sulfonate, sulfonamide, thioformacetal, formacetal, oxime, methyleneimino, methylenemethylimino, methylenehydrazo,

methylenedimethylhydrazo and methyleneoxymethylimino.

Replacement of the Ribophosphate Backbone

Scaffolds that can mimic nucleic acids can also be constructed wherein the phosphate linker and ribose sugar are replaced by nuclease resistant nucleoside or nucleotide surrogates. In some embodiments, the nucleobases can be tethered by a surrogate backbone. Examples can include, without limitation, the morpholino, cyclobutyl, pyrrolidine and peptide nucleic acid (PNA) nucleoside surrogates.

Sugar Modifications The modified nucleosides and modified nucleotides can include one or more modifications to the sugar group. For example, the 2' hydroxyl group (OH) can be modified or replaced with a number of different "oxy" or "deoxy" substituents. In some embodiments, modifications to the 2' hydroxyl group can enhance the stability of the nucleic acid since the hydroxyl can no longer be deprotonated to form a 2' -alkoxide ion. The 2' -alkoxide can catalyze degradation by intramolecular nucleophilic attack on the linker phosphorus atom.

Examples of "oxy"-2' hydroxyl group modifications can include alkoxy or aryloxy (OR, wherein "R" can be, e.g., alkyl, cycloalkyl, aryl, aralkyl, heteroaryl or a sugar);

polyethyleneglycols (PEG), 0(CH₂CH₂0)_nCH₂CH₂OR wherein R can be, e.g., H or optionally substituted alkyl, and n can be an integer from 0 to 20 (e.g., from 0 to 4, from 0 to 8, from 0 to 10, from 0 to 16, from 1 to 4, from 1 to 8, from 1 to 10, from 1 to 16, from 1 to 20, from 2 to 4, from 2 to 8, from 2 to 10, from 2 to 16, from 2 to 20, from 4 to 8, from 4 to 10, from 4 to 16, and from 4 to 20). In some embodiments, the "oxy"-2' hydroxyl group modification can include "locked" nucleic acids (LNA) in which the 2' hydroxyl can be connected, e.g., by a C_1-6 alkylene or Ci_6 heteroalkylene bridge, to the 4' carbon of the same ribose sugar, where exemplary bridges can include methylene, propylene, ether, or amino bridges; O-amino (wherein amino can be, e.g., NH₂; alkylamino, dialkylamino, heterocyclyl, arylamino, diarylamino, heteroarylamino, or diheteroarylamino, ethylenediamine, or polyamino) and aminoalkoxy, 0(CH₂)_n-amino, (wherein amino can be, e.g., NH₂; alkylamino, dialkylamino, heterocyclyl, arylamino, diarylamino, heteroarylamino, or diheteroarylamino, ethylenediamine, or polyamino). In some embodiments, the "oxy"-2' hydroxyl group modification can include the methoxyethyl group (MOE),

(OCH₂CH₂OCH₃, e.g., a PEG derivative).

"Deoxy" modifications can include hydrogen (i.e. deoxyribose sugars, e.g., at the overhang portions of partially ds RNA); halo (e.g., bromo, chloro, fluoro, or iodo); amino (wherein amino can be, e.g., NH₂; alkylamino, dialkylamino, heterocyclyl, arylamino, diarylamino, heteroarylamino, diheteroarylamino, or amino acid); NH(CH₂CH₂NH)_nCH₂CH₂- amino (wherein amino can be, e.g., as described herein), -NHC(0)R (wherein R can be, e.g., alkyl, cycloalkyl, aryl, aralkyl, heteroaryl or sugar), cyano; mercapto; alkyl-thio-alkyl;

thioalkoxy; and alkyl, cycloalkyl, aryl, alkenyl and alkynyl, which may be optionally substituted with e.g., an amino as described herein. The sugar group can also contain one or more carbons that possess the opposite stereochemical configuration than that of the corresponding carbon in ribose. Thus, a modified nucleic acid can include nucleotides containing e.g., arabinose, as the sugar. The nucleotide "monomer" can have an alpha linkage at the position on the sugar, e.g., alpha-nucleosides. The modified nucleic acids can also include "abasic" sugars, which lack a nucleobase at C- . These abasic sugars can also be further modified at one or more of the constituent sugar atoms. The modified nucleic acids can also include one or more sugars that are in the L form, e.g. L- nucleosides.

Generally, RNA includes the sugar group ribose, which is a 5-membered ring having an oxygen. Exemplary modified nucleosides and modified nucleotides can include, without limitation, replacement of the oxygen in ribose (e.g., with sulfur (S), selenium (Se), or alkylene, such as, e.g., methylene or ethylene); addition of a double bond (e.g., to replace ribose with cyclopentenyl or cyclohexenyl); ring contraction of ribose (e.g., to form a 4-membered ring of cyclobutane or oxetane); ring expansion of ribose (e.g., to form a 6- or 7-membered ring having an additional carbon or heteroatom, such as for example, anhydrohexitol, altritol, mannitol, cyclohexanyl, cyclohexenyl, and morpholino that also has a phosphoramidate backbone). In some embodiments, the modified nucleotides can include multicyclic forms (e.g., tricyclo; and "unlocked" forms, such as glycol nucleic acid (GNA) (e.g., R-GNA or S-GNA, where ribose is replaced by glycol units attached to phosphodiester bonds), threose nucleic acid (TNA, where ribose is replaced with a-L-threofuranosyl-(3'→2')).

Modifications on the Nucleobase

The modified nucleosides and modified nucleotides described herein, which can be incorporated into a modified nucleic acid, can include a modified nucleobase. Examples of nucleobases include, but are not limited to, adenine (A), guanine (G), cytosine (C), and uracil (U). These nucleobases can be modified or wholly replaced to provide modified nucleosides and modified nucleotides that can be incorporated into modified nucleic acids. The nucleobase of the nucleotide can be independently selected from a purine, a pyrimidine, a purine or pyrimidine analog. In some embodiments, the nucleobase can include, for example, naturally-occurring and synthetic derivatives of a base.

Uracil In some embodiments, the modified nucleobase is a modified uracil. Exemplary nucleobases and nucleosides having a modified uracil include without limitation pseudouridine (ψ), pyridin-4-one ribonucleoside, 5-aza-uridine, 6-aza-uridine, 2-thio-5-aza-uridine, 2-thio- uridine (s2U), 4-thio-uridine (s4U), 4-thio-pseudouridine, 2-thio-pseudouridine, 5-hydroxy- uridine (ho⁵U), 5-aminoallyl-uridine, 5-halo-uridine (e.g., 5-iodo-uridine or 5-bromo-uridine), 3-

3 5 5

methyl-uridine (m U), 5-methoxy-uridine (mo U), uridine 5-oxyacetic acid (cmo U), uridine 5- oxyacetic acid methyl ester (mcmo⁵U), 5-carboxymethyl-uridine (cm⁵U), 1-carboxymethyl- pseudouridine, 5-carboxyhydroxymethyl-uridine (chm⁵U), 5-carboxyhydroxymethyl-uridine methyl ester (mchm⁵U), 5-methoxycarbonylmethyl-uridine (mcm⁵U), 5- methoxycarbonylmethyl-2-thio-uridine (mcm⁵s2U), 5-aminomethyl-2-thio-uridine (nm⁵s2U), 5- methylaminomethyl-uridine (mnm⁵U), 5-methylaminomethyl-2-thio-uridine (mnm⁵s2U), 5-

5 2 5 methylaminomethyl-2-seleno-uridine (mnm se U), 5-carbamoylmethyl-uridine (ncm U), 5- carboxymethylaminomethyl-uridine (cmnm⁵U), 5-carboxymethylaminomethyl-2-thio-uridine (cmnm ⁵s2U), 5-propynyl-uridine, 1-propynyl-pseudouridine, 5-taurinomethyl-uridine (xcm⁵U),

1- taurinomethyl -pseudouridine, 5-taurinomethyl-2-thio-uridine(xm⁵s2U), l-taurinomethyl-4- thio-pseudouridine, 5-methyl-uridine (m⁵U, i.e., having the nucleobase deoxythymine), 1- methyl-pseudouridine (πι'ψ), 5-methyl-2-thio-uridine (m⁵s2U), l-methyl-4-thio-pseudouridine

2-thio-l-methyl- pseudouridine, 1 -methyl- 1 -deaza-pseudouridine, 2-thio- 1 -methyl- 1 -deaza-pseudouridine, dihydrouridine (D), dihydropseudouridine, 5,6-dihydrouridine, 5-methyl-dihydrouridine (m⁵D),

2- thio-dihydrouridine, 2-thio-dihydropseudouridine, 2-methoxy-uridine, 2-methoxy-4-thio- uridine, 4-methoxy-pseudouridine, 4-methoxy-2-thio-pseudouridine, Nl-methyl-pseudouridine,

3- (3-amino-3-carboxypropyl)uridine (acp U), l-methyl-3-(3-amino-3-

3 5

carboxypropyl)pseudouridine (acp ψ), 5-(isopentenylaminomethyl)uridine (inm U), 5- (isopentenylaminomethyl)-2-thio-uridine (inm⁵s2U), a-thio-uridine, 2'-0-methyl-uridine (Um), 5,2'-0-dimethyl-uridine (m⁵Um), 2'-0-methyl-pseudouridine (ψπι), 2-thio-2'-0-methyl-uridine (s2Um), 5-methoxycarbonylmethyl-2'-0-methyl -uridine (mem ⁵Um), 5-carbamoylmethyl-2'-0- methyl-uridine (ncm ⁵Um), 5-carboxymethylaminomethyl-2'-0-methyl-uridine (cmnm ⁵Um),

3 5

3,2'-0-dimethyl-uridine (m Um), 5-(isopentenylaminomethyl)-2'-0-methyl-uridine (inm Um), 1-thio-uridine, deoxythymidine, 2'-F-ara-uridine, 2'-F-uridine, 2'-OH-ara-uridine, 5-(2- carbomethoxyvinyl) uridine, 5-[3-(l-E-propenylamino)uridine, pyrazolo[3,4-d]pyrimidines, xanthine, and hypoxanthine.

Cytosine

In some embodiments, the modified nucleobase is a modified cytosine. Exemplary nucleobases and nucleosides having a modified cytosine include without limitation 5-aza- cytidine, 6-aza-cytidine, pseudoisocytidine, 3-methyl-cytidine (m C), N4-acetyl-cytidine (act), 5- formyl-cytidine (f⁵C), N4-methyl-cytidine (m⁴C), 5-methyl-cytidine (m⁵C), 5-halo-cytidine (e.g., 5-iodo-cytidine), 5-hydroxymethyl-cytidine (hm⁵C), 1-methyl-pseudoisocytidine, pyrrolo- cytidine, pyrrolo-pseudoisocytidine, 2-thio-cytidine (s2C), 2-thio-5-methyl-cytidine, 4-thio- pseudoisocytidine, 4-thio- 1-methyl-pseudoisocytidine, 4-thio-l -methyl- 1-deaza- pseudoisocytidine, 1 -methyl- 1-deaza-pseudoisocytidine, zebularine, 5-aza-zebularine, 5-methyl- zebularine, 5-aza-2-thio-zebularine, 2-thio-zebularine, 2-methoxy-cytidine, 2-methoxy- 5 -methyl- cytidine, 4-methoxy-pseudoisocytidine, 4-methoxy- 1-methyl-pseudoisocytidine, lysidine (k C), a-thio-cytidine, 2'-0-methyl-cytidine (Cm), 5,2'-0-dimethyl-cytidine (m⁵Cm), N4-acetyl-2'-0- methyl-cytidine (ac⁴Cm), N4,2'-0-dimethyl-cytidine (m⁴Cm), 5-formyl-2'-0-methyl-cytidine (f ⁵Cm), N4,N4,2'-0-trimethyl-cytidine (m⁴ ₂Cm), 1-thio-cytidine, 2'-F-ara-cytidine, 2'-F-cytidine, and 2'-OH-ara-cytidine.

Adenine

In some embodiments, the modified nucleobase is a modified adenine. Exemplary nucleobases and nucleosides having a modified adenine include without limitation 2-amino- purine, 2,6-diaminopurine, 2-amino-6-halo-purine (e.g., 2-amino-6-chloro-purine), 6-halo-purine (e.g., 6-chloro-purine), 2-amino-6-methyl-purine, 8-azido-adenosine, 7-deaza-adenosine, 7- deaza-8-aza-adenosine, 7-deaza-2-amino-purine, 7-deaza-8-aza-2-amino-purine, 7-deaza-2,6- diaminopurine, 7-deaza-8-aza-2,6-diaminopurine, 1 -methyl- adenosine (i A), 2-methyl- adenosine (m²A), N6-methyl-adenosine (m⁶A), 2-methylthio-N6-methyl-adenosine (ms2m⁶A), N6-isopentenyl-adenosine (i⁶A), 2-methylthio-N6-isopentenyl-adenosine (ms²i⁶A), N6-(cis- hydroxyisopentenyl)adenosine (io⁶A), 2-methylthio-N6-(cis-hydroxyisopentenyl)adenosine (ms2io⁶A), N6-glycinylcarbamoyl-adenosine (g⁶A), N6-threonylcarbamoyl-adenosine (t⁶A), N6- methyl-N6-threonylcarbamoyl-adenosine (m⁶t⁶A), 2-methylthio-N6-threonylcarbamoyl- adenosine (ms²g⁶A), N6,N6-dimethyl-adenosine (m⁶ ₂A), N6-hydroxynorvalylcarbamoyl- adenosine (hn⁶A), 2-methylthio-N6-hydroxynorvalylcarbamoyl-adenosine (ms2hn⁶A), N6- acetyl-adenosine (ac⁶A), 7-methyl-adenosine, 2-methylthio-adenosine, 2-methoxy-adenosine, a- thio-adenosine, 2'-0-methyl-adenosine (Am), N⁶,2'-0-dimethyl-adenosine (m⁶Am), N⁶-Methyl- 2'-deoxyadenosine, N6,N6,2'-0-trimethyl-adenosine (m⁶ ₂Am), l,2'-0-dimethyl-adenosine (i Am), 2'-0-ribosyladenosine (phosphate) (Ar(p)), 2-amino-N6-methyl -purine, 1-thio- adenosine, 8-azido-adenosine, 2'-F-ara-adenosine, 2'-F-adenosine, 2'-OH-ara-adenosine, and N6- ( 19- amino-pentaoxanonadecyl) - adeno sine .

Guanine

In some embodiments, the modified nucleobase is a modified guanine. Exemplary nucleobases and nucleosides having a modified guanine include without limitation inosine (I), 1- methyl-inosine (iVl), wyosine (imG), methylwyosine (mimG), 4-demethyl-wyosine (imG-14), isowyosine (imG2), wybutosine (yW), peroxywybutosine (o₂yW), hydroxy wybuto sine (OHyW), undermodified hydroxy wybuto sine (OHyW*), 7-deaza-guanosine, queuosine (Q),

epoxyqueuosine (oQ), galactosyl-queuosine (galQ), mannosyl-queuosine (manQ), 7-cyano-7- deaza-guanosine (preQ₀), 7-aminomethyl-7-deaza-guanosine (preQ , archaeosine (G⁺), 7-deaza- 8-aza-guanosine, 6-thio-guanosine, 6-thio-7-deaza-guanosine, 6-thio-7-deaza-8-aza-guanosine, 7-methyl-guanosine (m G), 6-thio-7-methyl-guanosine, 7-methyl-inosine, 6-methoxy-guanosine, l-methyl-guanosine (m'G), N2-methyl-guanosine (m 2 G), N2,N2-dimethyl-guanosine (m 2 ₂G),

N2,7-dimethyl-guanosine (m 2 ,7G), N2, N2,7-dimethyl-guanosine (m 2 ,2,7G), 8-oxo-guanosine, 7-methyl-8-oxo-guanosine, l-methyl-6-thio-guanosine, N2-methyl-6-thio-guanosine, N2,N2- dimethyl-6-thio-guanosine, a-thio-guanosine, 2'-0-methyl-guanosine (Gm), N2-methyl-2'-0- methyl-guanosine (m 2"Gm), N2,N2-dimethyl-2'-0-methyl- guano sine (m 2 ₂Gm), l-methyl-2'-0- methyl-guanosine (m'Gm), N2,7-dimethyl-2'-0-methyl-guanosine (m",7Gm), 2'-0-methyl- inosine (Im), l,2'-0-dimethyl-inosine (m'lm), 0⁶-phenyl-2'-deoxyinosine, 2'-0-ribosylguanosine (phosphate) (Gr(p)), 1-thio-guanosine, 0⁶-methyl- guanosine, 0⁶-Methyl-2'-deoxy guanosine, z - F-ara-guanosine, and 2'-F-guanosine.

Exemplary Modified gRNAs

In some embodiments, the modified nucleic acids can be modified gRNAs. It is to be understood that any of the gRNAs described herein can be modified in accordance with this section, including any gRNA that comprises a targeting domain from Tables 1A-1E, 2A-2E, 3A- 3D, 4A-4D, 5A-5E, 6A-6C, 7A-7D, 8A-8E, 9A-9B, lOA-lOC, 11A-11E, 12A-12C, 13A-13D, 14A-14E, 15A-15C, or 16A-16D, 17A-17E, 18A-18C, 19A-19D, 20A-20E, 21A-21B, 22A- 22D, 23A-23E, 24A-24D, 25A-25D, 26A-26E, 27A-27D, 28A-28D, 29A-29E, 30A-30B, 31A- 31D, 32A-32D, 33A-33B, 34A-34D, 35A-35D, 36A-36D, 37A-37D, 38A-38E, 39A-39D, 40A- 40D, 41A-41E, 42A-42D, 43A-43E, 44A-44G, 45A-45E, 46A-46E, 47A-47G, or 48A-48E.

Through experimentation (results not shown) we have found that the guide RNA (gRNA) component of the CRISPR/Cas system is more efficient at editing genes in T cells when it has been modified at or near its 5' end (e.g., when the 5' end of a gRNA is modified by the inclusion of a eukaryotic mRNA cap structure or cap analog). While not wishing to be bound by theory it is believed that these and other modified gRNAs described herein elicit a reduced innate immune response from certain circulatory cell types (e.g., T cells) and that this might be responsible for the observed improvements. The present invention encompasses the realization that minimizing the innate immune response of circulating cells (e.g., T cells) to gRNAs could be advantageous when using gRNAs to edit circulating cells (whether ex vivo or in vivo) and could also be advantageous when using gRNAs to edit non-circulating cells, e.g., when a gRNA is

administered systemically or locally for in vivo gene editing purposes. The present invention also encompasses the realization that the improvements observed with a 5' capped gRNA can be extended to gRNAs that have been modified in other ways to achieve the same type of structural or functional result (e.g., by the inclusion of modified nucleosides or nucleotides, or when an in vitro transcribed gRNA is modified by treatment with a phosphatase such as calf intestinal alkaline phosphatase to remove the 5' triphosphate group). While not wishing to be bound by theory, in some embodiments, the modified gRNAs described herein may contain one or more modifications (e.g., modified nucleosides or nucleotides) which introduce stability toward nucleases (e.g., by the inclusion of modified nucleosides or nucleotides and/or a 3' polyA tract).

Thus, in one aspect, methods and compositions discussed herein provide methods and compositions for gene editing by using gRNAs which have been modified at or near their 5' end (e.g., within 1-10, 1-5, or 1-2 nucleotides of their 5' end). In an embodiment, the 5' end of a gRNA is modified by the inclusion of a eukaryotic mRNA cap structure or cap analog (e.g., a G(5')ppp(5')G cap analog, a m7G(5')ppp(5')G cap analog, or a 3 '-0-Me-m7G(5')ppp(5')G anti reverse cap analog (ARC A)). The cap or cap analog can be included during either chemical synthesis or in vitro transcription of the gRNA. In an embodiment, an in vitro transcribed gRNA is modified by treatment with a phosphatase (e.g., calf intestinal alkaline phosphatase) to remove the 5' triphosphate group.

In another aspect, methods and compositions discussed herein provide methods and compositions for gene editing by using gRNAs which include one or more modified nucleosides or nucleotides that are described herein. In some embodiments, the inclusion of the one or more modified nucleosides or nucleotides causes the gRNA to elicit a reduced innate immune response in certain circulating cell types (e.g., T cells, macrophages, dendritic cells, and/or B cells) as compared to an otherwise unmodified gRNA.

While some of the exemplary modifications discussed in this section may be included at any position within the gRNA sequence, in some embodiments, a gRNA comprises a

modification at or near its 5' end (e.g., within 1-10, 1-5, or 1-2 nucleotides of its 5' end). In some embodiments, a gRNA comprises a modification at or near its 3' end (e.g., within 1-10, 1- 5, or 1-2 nucleotides of its 3' end). In some embodiments, a gRNA comprises both a

modification at or near its 5' end and a modification at or near its 3' end.

In an embodiment, the 3' end of a gRNA is modified by the addition of one or more (e.g., 25-200) adenine (A) residues. The polyA tract can be contained in the nucleic acid (e.g., plasmid, PCR product, viral genome) encoding the gRNA, or can be added to the gRNA during chemical synthesis, or following in vitro transcription using a polyadenosine polymerase (e.g., E. coli Poly(A)Polymerase).

In an embodiment, in vitro transcribed gRNA contains both a 5' cap structure or cap analog and a 3' polyA tract. In an embodiment, an in vitro transcribed gRNA is modified by treatment with a phosphatase (e.g., calf intestinal alkaline phosphatase) to remove the 5' triphosphate group and comprises a 3' polyA tract.

In some embodiments, gRNAs can be modified at a 3' terminal U ribose. For example, the two terminal hydroxyl groups of the U ribose can be oxidized to aldehyde groups and a concomitant opening of the ribose ring to afford a modified nucleoside as shown below:

wherein "U" can be an unmodified or modified uridine. In another embodiment, the 3' terminal U can be modified with a 2' 3' cyclic phosphate as shown below:

wherein "U" can be an unmodified or modified uridine.

In some embodiments, the gRNA molecules may contain 3' nucleotides which can be stabilized against degradation, e.g., by incorporating one or more of the modified nucleotides described herein. In this embodiment, e.g., uridines can be replaced with modified uridines, e.g., 5-(2-amino)propyl uridine, and 5-bromo uridine, or with any of the modified uridines described herein; adenosines, cytidines and guanosines can be replaced with modified adenosines, cytidines and guanosines, e.g., with modifications at the 8-position, e.g., 8-bromo guanosine, or with any of the modified adenosines, cytidines or guanosines described herein.

In some embodiments, sugar-modified ribonucleotides can be incorporated into the gRNA, e.g., wherein the 2' OH-group is replaced by a group selected from H, -OR, -R (wherein R can be, e.g., alkyl, cycloalkyl, aryl, aralkyl, heteroaryl or sugar), halo, -SH, -SR (wherein R can be, e.g., alkyl, cycloalkyl, aryl, aralkyl, heteroaryl or sugar), amino (wherein amino can be, e.g., NH₂; alkylamino, dialkylamino, heterocyclylamino, arylamino, diarylamino,

heteroarylamino, diheteroarylamino, or amino acid); or cyano (-CN). In some embodiments, the phosphate backbone can be modified as described herein, e.g., with a phosphothioate group. In some embodiments, one or more of the nucleotides of the gRNA can each independently be a modified or unmodified nucleotide including, but not limited to 2' -sugar modified, such as, 2'-0- methyl, 2'-0-methoxyethyl, or 2'-Fluoro modified including, e.g., 2'-F or 2'-0-methyl, adenosine (A), 2'-F or 2'-0-methyl, cytidine (C), 2'-F or 2'-0-methyl, uridine (U), 2'-F or 2'-0- methyl, thymidine (T), 2'-F or 2'-0-methyl, guanosine (G), 2'-0-methoxyethyl-5-methyluridine (Teo), 2'-0-methoxyethyladenosine (Aeo), 2'-0-methoxyethyl-5-methylcytidine (m5Ceo), and any combinations thereof.

In some embodiments, a gRNA can include "locked" nucleic acids (LNA) in which the 2' OH-group can be connected, e.g., by a CI -6 alkylene or CI -6 heteroalkylene bridge, to the 4' carbon of the same ribose sugar, where exemplary bridges can include methylene, propylene, ether, or amino bridges; O-amino (wherein amino can be, e.g., NH₂; alkylamino, dialkylamino, heterocyclylamino, arylamino, diarylamino, heteroarylamino, or diheteroarylamino,

ethylenediamine, or polyamino) and aminoalkoxy or 0(CH₂)_n-amino (wherein amino can be, e.g., NH₂; alkylamino, dialkylamino, heterocyclylamino, arylamino, diarylamino,

heteroarylamino, or diheteroarylamino, ethylenediamine, or polyamino).

In some embodiments, a gRNA can include a modified nucleotide which is multicyclic (e.g., tricyclo; and "unlocked" forms, such as glycol nucleic acid (GNA) (e.g., R-GNA or S- GNA, where ribose is replaced by glycol units attached to phosphodiester bonds), or threose nucleic acid (TNA, where ribose is replaced with a-L-threofuranosyl-(3'→2')).

Generally, gRNA molecules include the sugar group ribose, which is a 5-membered ring having an oxygen. Exemplary modified gRNAs can include, without limitation, replacement of the oxygen in ribose (e.g., with sulfur (S), selenium (Se), or alkylene, such as, e.g., methylene or ethylene); addition of a double bond (e.g., to replace ribose with cyclopentenyl or cyclohexenyl); ring contraction of ribose (e.g., to form a 4-membered ring of cyclobutane or oxetane); ring expansion of ribose (e.g., to form a 6- or 7-membered ring having an additional carbon or heteroatom, such as for example, anhydrohexitol, altritol, mannitol, cyclohexanyl, cyclohexenyl, and morpholino that also has a phosphoramidate backbone). Although the majority of sugar analog alterations are localized to the 2' position, other sites are amenable to modification, including the 4' position. In an embodiment, a gRNA comprises a 4'-S, 4'-Se or a 4'-C- aminomethyl-2' -O-Me modification.

In some embodiments, deaza nucleotides, e.g., 7-deaza-adenosine, can be incorporated into the gRNA. In some embodiments, O- and N-alkylated nucleotides, e.g., N6-methyl adenosine, can be incorporated into the gRNA. In some embodiments, one or more or all of the nucleotides in a gRNA molecule are deoxynucleotides.

miRNA binding sites

microRNAs (or miRNAs) are naturally occurring cellular 19-25 nucleotide long noncoding RNAs. They bind to nucleic acid molecules having an appropriate miRNA binding site, e.g., in the 3' UTR of an mRNA, and down-regulate gene expression. While not wishing to be bound by theory it is believed that the down regulation is either by reducing nucleic acid molecule stability or by inhibiting translation. An RNA species disclosed herein, e.g., an mRNA encoding Cas9 can comprise an miRNA binding site, e.g., in its 3'UTR. The miRNA binding site can be selected to promote down regulation of expression is a selected cell type. By way of example, the incorporation of a binding site for miR-122, a microRNA abundant in liver, can inhibit the expression of the gene of interest in the liver.

Examples

The following Examples are merely illustrative and are not intended to limit the scope or content of the invention in any way.

Example 1: Evaluation of candidate guide RNAs (gRNAs)

The suitability of candidate gRNAs can be evaluated as described in this example.

Although described for a chimeric gRNA, the approach can also be used to evaluate modular gRNAs.

Cloning gRNAs into Vectors

For each gRNA, a pair of overlapping oligonucleotides is designed and obtained.

Oligonucleotides are annealed and ligated into a digested vector backbone containing an upstream U6 promoter and the remaining sequence of a long chimeric gRNA. Plasmid is sequence-verified and prepped to generate sufficient amounts of transfection-quality DNA. Alternate promoters maybe used to drive in vivo transcription (e.g. HI promoter) or for in vitro transcription (e.g., a T7 promoter).

Cloning gRNAs in linear dsDNA molecule (STITCHR)

For each gRNA, a single oligonucleotide is designed and obtained. The U6 promoter and the gRNA scaffold (e.g. including everything except the targeting domain, e.g., including sequences derived from the crRNA and tracrRNA, e.g., including a first complementarity domain; a linking domain; a second complementarity domain; a proximal domain; and a tail domain) are separately PCR amplified and purified as dsDNA molecules. The gRNA-specific oligonucleotide is used in a PCR reaction to stitch together the U6 and the gRNA scaffold, linked by the targeting domain specified in the oligonucleotide. Resulting dsDNA molecule (STITCHR product) is purified for transfection. Alternate promoters may be used to drive in vivo transcription (e.g., HI promoter) or for in vitro transcription (e.g., T7 promoter). Any gRNA scaffold may be used to create gRNAs compatible with Cas9s from any bacterial species.

Initial gRNA Screen

Each gRNA to be tested is transfected, along with a plasmid expressing Cas9 and a small amount of a GFP-expressing plasmid into human cells. In preliminary experiments, these cells can be immortalized human cell lines such as 293T, K562 or U20S. Alternatively, primary human cells may be used. In this case, cells may be relevant to the eventual therapeutic cell target (for example, an erythroid cell). The use of primary cells similar to the potential therapeutic target cell population may provide important information on gene targeting rates in the context of endogenous chromatin and gene expression.

Transfection may be performed using lipid transfection (such as Lipofectamine or Fugene) or by electroporation (such as Lonza Nucleofection). Following transfection, GFP expression can be determined either by fluorescence microscopy or by flow cytometry to confirm consistent and high levels of transfection. These preliminary transfections can comprise different gRNAs and different targeting approaches (17-mers, 20-mers, nuclease, dual-nickase, etc.) to determine which gRNAs/combinations of gRNAs give the greatest activity.

Efficiency of cleavage with each gRNA may be assessed by measuring NHEJ-induced indel formation at the target locus by a T7El-type assay or by sequencing. Alternatively, other mismatch- sensitive enzymes, such as Cell/Surveyor nuclease, may also be used.

For the T7E1 assay, PCR amplicons are approximately 500-700bp with the intended cut site placed asymmetrically in the amplicon. Following amplification, purification and size- verification of PCR products, DNA is denatured and re-hybridized by heating to 95 °C and then slowly cooling. Hybridized PCR products are then digested with T7 Endonuclease I (or other mismatch- sensitive enzyme) which recognizes and cleaves non-perfectly matched DNA. If indels are present in the original template DNA, when the amplicons are denatured and re- annealed, this results in the hybridization of DNA strands harboring different indels and therefore lead to double- stranded DNA that is not perfectly matched. Digestion products may be visualized by gel electrophoresis or by capillary electrophoresis. The fraction of DNA that is cleaved (density of cleavage products divided by the density of cleaved and uncleaved) may be used to estimate a percent NHEJ using the following equation: NHEJ = (1-(1 -fraction cleaved)'⁷²). The T7E1 assay is sensitive down to about 2-5% NHEJ. Sequencing may be used instead of, or in addition to, the T7E1 assay. For Sanger sequencing, purified PCR amplicons are cloned into a plasmid backbone, transformed, miniprepped and sequenced with a single primer. Sanger sequencing may be used for determining the exact nature of indels after determining the NHEJ rate by T7E1.

Sequencing may also be performed using next generation sequencing techniques. When using next generation sequencing, amplicons may be 300-500bp with the intended cut site placed asymmetrically. Following PCR, next generation sequencing adapters and barcodes (for example Illumina multiplex adapters and indexes) may be added to the ends of the amplicon, e.g., for use in high throughput sequencing (for example on an Illumina MiSeq). This method allows for detection of very low NHEJ rates.

Example 2: Assessment of Gene Targeting by NHEJ

The gRNAs that induce the greatest levels of NHEJ in initial tests can be selected for further evaluation of gene targeting efficiency. In this case, cells are derived from disease subjects and, therefore, harbor the relevant mutation.

Following transfection (usually 2-3 days post-transfection,) genomic DNA may be isolated from a bulk population of transfected cells and PCR may be used to amplify the target region. Following PCR, gene targeting efficiency to generate the desired mutations (either knockout of a target gene or removal of a target sequence motif) may be determined by sequencing. For Sanger sequencing, PCR amplicons may be 500-700 bp long. For next generation sequencing, PCR amplicons may be 300-500 bp long. If the goal is to knockout gene function, sequencing may be used to assess what percent of alleles have undergone NHEJ- induced indels that result in a frameshift or large deletion or insertion that would be expected to destroy gene function. If the goal is to remove a specific sequence motif, sequencing may be used to assess what percent of alleles have undergone NHEJ-induced deletions that span this sequence.

Example 3: Assessment of Gene Targeting by HDR

The gRNAs that induce the greatest levels of NHEJ in initial tests can be selected for further evaluation of gene targeting efficiency. In this case, cells are derived from disease subjects and, therefore, harbor the relevant mutation. Following transfection (usually 2-3 days post-transfection,) genomic DNA may be isolated from a bulk population of transfected cells and PCR may be used to amplify the target region. Following PCR, gene targeting efficiency can be determined by several methods.

Determination of gene targeting frequency involves measuring the percentage of alleles that have undergone homologous directed repair (HDR) with the donor template and which therefore have incorporated desired correction. If the desired HDR event creates or destroys a restriction enzyme site, the frequency of gene targeting may be determined by a RFLP assay. If no restriction site is created or destroyed, sequencing may be used to determine gene targeting frequency. If a RFLP assay is used, sequencing may still be used to verify the desired HDR event and ensure that no other mutations are present. At least one of the primers is placed in the endogenous gene sequence outside of the region included in the homology arms, which prevents amplification of donor template still present in the cells. Therefore, the length of the homology arms present in the donor template may affect the length of the PCR amplicon. PCR amplicons can either span the entire donor region (both primers placed outside the homology arms) or they can span only part of the donor region and a single junction between donor and endogenous DNA (one internal and one external primer). If the amplicons span less than entire donor region, two different PCRs should be used to amplify and sequence both the 5' and the 3' junction.

If the PCR amplicon is short (less than 600bp) it is possible to use next generation sequencing. Following PCR, next generation sequencing adapters and barcodes (for example Illumina multiplex adapters and indexes) may be added to the ends of the amplicon, e.g., for use in high throughput sequencing (for example on an Illumina MiSeq). This method allows for detection of very low gene targeting rates.

If the PCR amplicon is too long for next generation sequencing, Sanger sequencing can be performed. For Sanger sequencing, purified PCR amplicons will be cloned into a plasmid backbone (for example, TOPO cloned using the LifeTech Zero Blunt^® TOPO^® cloning kit), transformed, miniprepped and sequenced.

Incorporation by Reference

All publications, patents, and patent applications mentioned herein are hereby

incorporated by reference in their entirety as if each individual publication, patent or patent application was specifically and individually indicated to be incorporated by reference. In case of conflict, the present application, including any definitions herein, will control.

Equivalents

Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. Such equivalents are intended to be encompassed by the following claims.

Claims

CLAIMS What is claimed is:

1. A gRNA molecule comprising a targeting domain which is complementary with a target domain from the CFTR or SCNN1A gene.

2. The gRNA molecule of claim 1, wherein said targeting domain is configured to provide a cleavage event selected from a double strand break and a single strand break, within 500, 400, 300, 200, 100, 50, 25 or 10 nucleotides of a CF target mutant position or a CF target knockout position.

3. The gRNA molecule of claim 1 or 2, wherein said targeting domain is configured to target an early coding region of the SCNN1A gene.

4. The gRNA molecule of claim 1 or 2, wherein said targeting domain is configured to target an intronic region of the CFTR gene.

5. The gRNA molecule of claim 1 or 2, wherein said targeting domain is configured to target a mutation in the CFTR gene.

6. The gRNA molecule of claim 1, wherein said targeting domain is configured to target an enzymatically inactive Cas9 (eiCas9) molecule or an eiCas9 fusion protein, sufficiently close to a CF target knockdown position to reduce, decrease or repress expression of the SCNN1A gene.

7. The gRNA molecule of claim 1, 2, or 6, wherein said targeting domain is configured to target the promoter region of the SCNN1A gene.

8. The gRNA molecule of any of claims 1-7, wherein said targeting domain comprises a sequence that is the same as, or differs by no more than 3 nucleotides from, a targeting domain sequence from any of Tables 1A-1E, 2A-2E, 3A-3D, 4A-4D, 5A-5E, 6A-6C, 7A-7D, 8A-8E, 9A-9B, lOA-lOC, 11A-11E, 12A-12C, 13A-13D, 14A-14E, 15A-15C, or 16A-16D, 17A-17E, 18A-18C, 19A-19D, 20A-20E, 21A-21B, 22A-22D, 23A-23E, 24A-24D, 25A-25D, 26A-26E, 27A-27D, 28A-28D, 29A-29E, 30A-30B, 31A-31D, 32A-32D, 33A-33B, 34A-34D, 35A-35D, 36A-36D, 37A-37D, 38A-38E, 39A-39D, 40A-40D, 41A-41E, 42A-42D, 43A-43E, 44A-44G, 45A-45E, 46A-46E, 47A-47G, or 48A-48E.

9. The gRNA molecule of any of claims 1-3 or 6-8, wherein said targeting domain is selected from those in Tables 3A-3D, 43A-43E, 44A-44G, 45A-45E, 46A-46E, 47A- 47G, or 48A-48E.

10. The gRNA molecule of any of claims 1, 2, 4, 5 or 8, wherein said targeting domain is selected from those in Tables 1A-1E, 2A-2E, 4A-4D, 5A-5E, 6A-6C, 7A-7D, 8A-8E, 9A-9B, lOA-lOC, 11A-11E, 12A-12C, 13A-13D, 14A-14E, 15A-15C, or 16A-16D, 17A-17E, 18A-18C, 19A-19D, 20A-20E, 21A-21B, 22A-22D, 23A-23E, 24A-24D, 25A-25D, 26A-26E, 27A-27D, 28A-28D, 29A-29E, 30A-30B, 31A-31D, 32A-32D, 33A-33B, 34A-34D, 35A-35D, 36A-36D, 37A-37D, 38A-38E, 39A-39D, 40A-40D, 41A-41E, or 42A-42D.

11. The gRNA molecule of any of claims 1, 2, 4, 5 or 8, wherein said targeting domain is selected from those in Tables 37A-37D, 38A-38E, 39A-39D, 40A-40D, 41A-41E, or 42A-42D.

12. The gRNA molecule of any of claims 1, 2, 5 or 8, wherein said targeting domain is

selected from those in those in Tables 1A-1E, 2A-2E, 4A-4D, 5A-5E, 6A-6C, 7A-7D, 8A-8E, 9A-9B, lOA-lOC, 11A-11E, 12A-12C, 13A-13D, 14A-14E, 15A-15C, or 16A- 16D, 17A-17E, 18A-18C, 19A-19D, 20A-20E, 21A-21B, 22A-22D, 23A-23E, 24A-24D, 25A-25D, 26A-26E, 27A-27D, 28A-28D, 29A-29E, 30A-30B, 31A-31D, 32A-32D, 33A-33B, 34A-34D, 35A-35D, or 36A-36D.

13. The gRNA molecule of any of claims 1-12, wherein said gRNA is a modular gRNA

molecule.

14. The gRNA molecule of any of claimsl-12, wherein said gRNA is a chimeric gRNA

molecule.

15. The gRNA molecule of any of claims 1-14, wherein said targeting domain is 16

nucleotides or more in length.

16. The gRNA molecule of any of claims 1-15, wherein said targeting domain is 16

nucleotides in length.

17. The gRNA molecule of any of claims 1-16, wherein said targeting domain is 17 or 18 nucleotides in length.

18. The gRNA molecule of any of claims 1-17, wherein said targeting domain is 19

nucleotides in length.

19. The gRNA molecule of any of claims 1-18, wherein said targeting domain is 20 nucleotides in length.

20. The gRNA molecule of any of claims 1-19, wherein said targeting domain is 21 nucleotides in length.

21. The gRNA molecule of any of claims 1-20, wherein said targeting domain is 22 nucleotides in length.

22. The gRNA molecule of any of claims 1-21, wherein said targeting domain is 23 nucleotides in length.

23. The gRNA molecule of any of claims 1-22, wherein said targeting domain is 24 nucleotides in length.

24. The gRNA molecule of any of claims 1-23, wherein said targeting domain is 25 nucleotides in length.

25. The gRNA molecule of any of claims 1-24, wherein said targeting domain is 26 nucleotides in length.

26. The gRNA molecule of any of claims 1-25, comprising from 5' to 3':

a targeting domain;

a first complementarity domain;

a linking domain;

a second complementarity domain;

a proximal domain; and

a tail domain.

27. The gRNA molecule of any of claims 1-26, comprising:

a linking domain of no more than 25 nucleotides in length;

a proximal and tail domain, that taken together, are at least 20 nucleotides length; and

a targeting domain of 17 or 18 nucleotides in length.

28. The gRNA molecule of any of claims 1-27, comprising:

a linking domain of no more than 25 nucleotides in length;

a proximal and tail domain, that taken together, are at least 25 nucleotides length; and

a targeting domain of 17 or 18 nucleotides in length.

29. The gRNA molecule of any of claims 1-28, comprising:

a linking domain of no more than 25 nucleotides in length;

a proximal and tail domain, that taken together, are at least 30 nucleotides in length; and

a targeting domain of 17 nucleotides in length.

30. The gRNA molecule of any of claims 1-29, comprising:

a linking domain of no more than 25 nucleotides in length;

a proximal and tail domain, that taken together, are at least 40 nucleotides in length; and

a targeting domain of 17 nucleotides in length.

31. A nucleic acid that comprises: (a) sequence that encodes a gRNA molecule comprising a targeting domain that is complementary with a CF target domain in the CFTR gene or SCNN1A gene.

32. The nucleic acid of claim 31, wherein said gRNA molecule is a gRNA molecule of any of claims 1-30.

33. The nucleic acid of claim 31 or 32, wherein said targeting domain is configured to

provide a cleavage event selected from a double strand break and a single strand break, within 500, 400, 300, 200, 100, 50, 25 or 10 nucleotides of the CF target mutant position or the CF target knockout position.

34. The nucleic acid of any of claims 31-33, wherein said targeting domain is configured to target an early coding region of the SCNN1A gene.

35. The nucleic acid of any of claims 31-33, wherein said targeting domain is configured to target an intronic region of the CFTR gene.

36. The nucleic acid of any of claims 31-33, wherein said targeting domain is configured to target a mutation in the CFTR gene.

37. The nucleic acid of claim 31 or 32, wherein said targeting domain is configured to target an enzymatically inactive Cas9 (eiCas9) molecule or an eiCas9 fusion protein, sufficiently close to a CF target knockdown position to reduce, decrease or repress expression of the SCNN1A gene.

38. The nucleic acid of claim 31, 32 or 37, wherein said targeting domain is configured to target the promoter region of the SCNN1A gene.

39. The nucleic acid of any of claims 31-38, wherein said targeting domain comprises a sequence that is the same as, or differs by no more than 3 nucleotides from, a targeting domain sequence from any of Tables 1A-1E, 2A-2E, 3A-3D, 4A-4D, 5A-5E, 6A-6C, 7A-7D, 8A-8E, 9A-9B, lOA-lOC, 11A-11E, 12A-12C, 13A-13D, 14A-14E, 15A-15C, or 16A-16D, 17A-17E, 18A-18C, 19A-19D, 20A-20E, 21A-21B, 22A-22D, 23A-23E, 24A-24D, 25A-25D, 26A-26E, 27A-27D, 28A-28D, 29A-29E, 30A-30B, 31A-31D, 32A-32D, 33A-33B, 34A-34D, 35A-35D, 36A-36D, 37A-37D, 38A-38E, 39A-39D, 40A-40D, 41A-41E, 42A-42D, 43A-43E, 44A-44G, 45A-45E, 46A-46E, 47A-47G, or 48A-48E.

40. The nucleic acid of any of claims 31-38, wherein said targeting domain comprises a

sequence that is the same as a targeting domain sequence from any of Tables 1A-1E, 2A- 2E, 3A-3D, 4A-4D, 5A-5E, 6A-6C, 7A-7D, 8A-8E, 9A-9B, lOA-lOC, 11A-11E, 12A- 12C, 13A-13D, 14A-14E, 15A-15C, or 16A-16D, 17A-17E, 18A-18C, 19A-19D, 20A- 20E, 21A-21B, 22A-22D, 23A-23E, 24A-24D, 25A-25D, 26A-26E, 27A-27D, 28A-28D, 29A-29E, 30A-30B, 31A-31D, 32A-32D, 33A-33B, 34A-34D, 35A-35D, 36A-36D, 37A-37D, 38A-38E, 39A-39D, 40A-40D, 41A-41E, 42A-42D, 43A-43E, 44A-44G, 45A-45E, 46A-46E, 47A-47G, or 48A-48E.

41. The nucleic acid of any of claims 31-40, wherein said gRNA is a modular gRNA

molecule.

42. The nucleic acid of any of claims 31-40, wherein said gRNA is a chimeric gRNA

molecule.

43. The nucleic acid of any of claims 31-42, wherein said targeting domain is 16 nucleotides or more in length.

44. The nucleic acid of any of claims 31-43, wherein said targeting domain is 17 nucleotides in length.

45. The nucleic acid of any of claims 31-44, wherein said targeting domain is 18 nucleotides in length.

46. The nucleic acid of any of claims 31-45, wherein said targeting domain is 19 nucleotides in length.

47. The nucleic acid of any of claims 31-46, wherein said targeting domain is 20 nucleotides in length.

48. The nucleic acid of any of claims 31-47, wherein said targeting domain is 21 nucleotides in length.

49. The nucleic acid of any of claims 31-48, wherein said targeting domain is 22 nucleotides in length.

50. The nucleic acid of any of claims 31-49, wherein said targeting domain is 23 nucleotides in length.

51. The nucleic acid of any of claims 31-50, wherein said targeting domain is 24 nucleotides in length.

52. The nucleic acid of any of claims 31-51, wherein said targeting domain is 25 nucleotides in length.

53. The nucleic acid of any of claims 31-52, wherein said targeting domain is 26 nucleotides in length.

54. The nucleic acid of any of claims 31-53, comprising from 5' to 3' :

a targeting domain;

a first complementarity domain;

a linking domain;

a second complementarity domain;

a proximal domain; and

a tail domain.

55. The nucleic acid of any of claims 31-54, comprising:

a linking domain of no more than 25 nucleotides in length;

a proximal and tail domain, that taken together, are at least 20 nucleotides in length; and a targeting domain of 17 or 18 nucleotides in length.

56. The nucleic acid of any of claims 31-55, comprising:

a linking domain of no more than 25 nucleotides in length;

a proximal and tail domain, that taken together, are at least 25 nucleotides in length; and a targeting domain of 17 or 18 nucleotides in length.

57. The nucleic acid of any of claims 31-56, comprising:

a linking domain of no more than 25 nucleotides in length;

a proximal and tail domain, that taken together, are at least 30 nucleotides in length; and a targeting domain of 17 nucleotides in length.

58. The nucleic acid of any of claims 31-57, comprising:

a linking domain of no more than 25 nucleotides in length;

a proximal and tail domain, that taken together, are at least 40 nucleotides in length; and a targeting domain of 17 nucleotides in length.

59. The nucleic acid of any of claims 31-58, further comprising: (b) sequence that encodes a Cas9 molecule.

60. The nucleic acid of claim 59, wherein said Cas9 molecule is an eaCas9 molecule.

61. The nucleic acid of claim 60, wherein said eaCas9 molecule comprises a nickase

molecule.

62. The nucleic acid of claim 60, wherein said eaCas9 molecule forms a double strand break in a target nucleic acid.

63. The nucleic acid of any of claims 60-61, wherein said eaCas9 molecule forms a single strand break in a target nucleic acid.

64. The nucleic acid of any of claims 60, 61 or 63, wherein said single strand break is formed in the strand of the target nucleic acid to which the targeting domain of said gRNA molecule is complementary.

65. The nucleic acid of any of claims 60, 61 or 63, wherein said single strand break is formed in the strand of the target nucleic acid other than the strand to which to which the targeting domain of said gRNA is complementary.

66. The nucleic acid of any of claims 60, 61 or 63, wherein said eaCas9 molecule comprises HNH-like domain cleavage activity but has no, or no significant, N-terminal RuvC-like domain cleavage activity.

67. The nucleic acid of any of claims 60, 61, 63 or 66, wherein said eaCas9 molecule is an HNH-like domain nickase.

68. The nucleic acid of any of claims 60, 61, 63, 66, or 67, wherein said eaCas9 molecule comprises a mutation at D10.

69. The nucleic acid of any of claims 60, 61, or 63, wherein said eaCas9 molecule comprises N-terminal RuvC-like domain cleavage activity but has no, or no significant, HNH-like domain cleavage activity.

70. The nucleic acid of any of claims 60, 61, 63 or 69, wherein said eaCas9 molecule is an N- terminal RuvC-like domain nickase.

71. The nucleic acid of any of claims 60, 61, 63, 69 or 70, wherein said eaCas9 molecule comprises a mutation at H840 or N863.

72. The nucleic acid of claim 59, wherein said Cas9 molecule is an eiCas9 molecule.

73. The nucleic acid of claim 72, wherein said Cas9 molecule is an eiCas9-fusion protein molecule.

74. The nucleic acid of claim 72 or 73, wherein the eiCas9 fusion protein molecule is an eiCas9-transcription repressor domain fusion or eiCas9-chormatin modifying protein fusion.

75. The nucleic acid of any of claims 31-73, further comprising: (c) sequence that encodes a second gRNA molecule described herein having a targeting domain that is

complementary to a second target domain of the CFTR gene or SCNN1A gene.

76. The nucleic acid of claim 75, wherein said second gRNA molecule is a gRNA molecule of any of claims 1-30.

77. The nucleic acid of claim 75 or 76, wherein said targeting domain of said second gRNA is configured to provide a cleavage event selected from a double strand break and a single strand break, within 500, 400, 300, 200, 100, 50, 25 or 10 nucleotides of the CF target mutant position or the CF target knockout position.

78. The nucleic acid of any of claims 75-77, wherein said targeting domain of said second gRNA moelecule is configured to target an early coding region of the SCNN1A gene.

79. The nucleic acid of any of claims 75-77, wherein said targeting domain of said second gRNA moelecule is configured to target a mutation in the CFTR gene.

80. The nucleic acid of claim 75 or 76, wherein said targeting domain is configured to target an enzymatically inactive Cas9 (eiCas9) molecule or an eiCas9 fusion protein, sufficiently close to a CF target knockdown position to reduce, decrease or repress expression of the SCNN1A gene.

81. The nucleic acid of claim 75, 76 or 80, wherein said targeting domain of said second gRNA molecule is configured to target the promoter region of the SCNN1A gene.

82. The nucleic acid of any one of claims 75-81, wherein said targeting domain of said

second gRNA comprises a sequence that is the same as, or differs by no more than 3 nucleotides from, a targeting domain sequence from any of Tables 1A-1E, 2A-2E, 3A- 3D, 4A-4D, 5A-5E, 6A-6C, 7A-7D, 8A-8E, 9A-9B, lOA-lOC, 11A-11E, 12A-12C, 13A-13D, 14A-14E, 15A-15C, or 16A-16D, 17A-17E, 18A-18C, 19A-19D, 20A-20E, 21A-21B, 22A-22D, 23A-23E, 24A-24D, 25A-25D, 26A-26E, 27A-27D, 28A-28D, 29A-29E, 30A-30B, 31A-31D, 32A-32D, 33A-33B, 34A-34D, 35A-35D, 36A-36D, 37A-37D, 38A-38E, 39A-39D, 40A-40D, 41A-41E, 42A-42D, 43A-43E, 44A-44G, 45A-45E, 46A-46E, 47A-47G, or 48A-48E.

83. The nucleic acid of any one of claims 75-80, wherein said targeting domain of said

second gRNA is selected from those in Tables 1A-1E, 2A-2E, 3A-3D, 4A-4D, 5A-5E, 6A-6C, 7A-7D, 8A-8E, 9A-9B, lOA-lOC, 11A-11E, 12A-12C, 13A-13D, 14A-14E, 15A-15C, or 16A-16D, 17A-17E, 18A-18C, 19A-19D, 20A-20E, 21A-21B, 22A-22D, 23A-23E, 24A-24D, 25A-25D, 26A-26E, 27A-27D, 28A-28D, 29A-29E, 30A-30B, 31A-31D, 32A-32D, 33A-33B, 34A-34D, 35A-35D, 36A-36D, 37A-37D, 38A-38E, 39A-39D, 40A-40D, 41A-41E, 42A-42D, 43A-43E, 44A-44G, 45A-45E, 46A-46E, 47A-47G, or 48A-48E.

84. The nucleic acid of any of claims 75-83, wherein said second gRNA molecule is a

modular gRNA molecule.

85. The nucleic acid of any of claims 75-83, wherein said second gRNA molecule is a

chimeric gRNA molecule.

86. The nucleic acid of any of claims 75-85, wherein said targeting domain is 16 nucleotides or more in length.

87. The nucleic acid of any of claims 75-86, wherein said targeting domain is 17 nucleotides in length.

88. The nucleic acid of any of claims 75-87, wherein said targeting domain is 18 nucleotides in length.

89. The nucleic acid of any of claims 75-88, wherein said targeting domain is 19 nucleotides in length.

90. The nucleic acid of any of claims 75-89, wherein said targeting domain is 20 nucleotides in length.

91. The nucleic acid of any of claims 75-90, wherein said targeting domain is 21 nucleotides in length.

92. The nucleic acid of any of claims 75-91, wherein said targeting domain is 22 nucleotides in length.

93. The nucleic acid of any of claims 75-92, wherein said targeting domain is 23 nucleotides in length.

94. The nucleic acid of any of claims 75-93, wherein said targeting domain is 24 nucleotides in length.

95. The nucleic acid of any of claims 75-94, wherein said targeting domain is 25 nucleotides in length.

96. The nucleic acid of any of claims 75-95, wherein said targeting domain is 26 nucleotides in length.

97. The nucleic acid of any of claims 75-96, wherein said second gRNA molecule comprises from 5' to 3':

a targeting domain;

a first complementarity domain;

a linking domain;

a second complementarity domain;

a proximal domain; and

a tail domain.

98. The nucleic acid of any of claims 75-97, wherein said second gRNA molecule comprises: a linking domain of no more than 25 nucleotides in length;

a proximal and tail domain, that taken together, are at least 20 nucleotides in length; and a targeting domain of 17 or 18 nucleotides in length.

99. The nucleic acid of any of claims 75-98, wherein said second molecule gRNA molecule comprises:

a linking domain of no more than 25 nucleotides in length;

a proximal and tail domain, that taken together, are at least 25 nucleotides in length; and a targeting domain of 17 or 18 nucleotides in length.

100. The nucleic acid of any of claims 75-99, wherein said second gRNA molecule comprises:

a linking domain of no more than 25 nucleotides in length;

a proximal and tail domain, that taken together, are at least 30 nucleotides in length; and a targeting domain of 17 nucleotides in length.

101. The nucleic acid of any of claims 75-100, wherein said second gRNA molecule comprises:

a linking domain of no more than 25 nucleotides in length;

a proximal and tail domain, that taken together, are at least 40 nucleotides in length; and a targeting domain of 17 nucleotides in length.

102. The nucleic acid of any of claims 75-101, further comprising a third gRNA

molecule.

103. The nucleic acid of claim 102, further comprising a fourth gRNA molecule.

104. The nucleic acid of claim 31, further comprising: (b) sequence that encodes a Cas9 molecule of any of claims 59-74.

105. The nucleic acid of claim 104, wherein said nucleic acid does not comprise (c) a sequence that encodes a second gRNA molecule.

106. The nucleic acid of claim 104, wherein each of (a) and (b) is present on the same nucleic acid molecule.

107. The nucleic acid of claim 106, wherein said nucleic acid molecule is an AAV vector.

108. The nucleic acid of any of claims 59-105, wherein: (a) is present on a first nucleic acid molecule; and (b) is present on a second nucleic acid molecule.

109. The nucleic acid of claim 108, wherein said first and second nucleic acid

molecules are AAV vectors.

110. The nucleic acid of claim 104, further comprising (c) a sequence that encodes a second gRNA molecule of any of claims 1-30.

111. The nucleic acid of any of claims 31103, 108, or 109, wherein each of (a) and (c) is present on the same nucleic acid molecule.

112. The nucleic acid of claim 111, wherein said nucleic acid molecule is an AAV vector.

113. The nucleic acid any of claims 31-103, 108, or 109, wherein: (a) is present on a first nucleic acid molecule; and (c) is present on a second nucleic acid molecule.

114. The nucleic acid of claim 113, wherein said first and second nucleic acid

molecules are AAV vectors.

115. The nucleic acid of claim 31, further comprising: (b) sequence that encodes a Cas9 molecule of any of claims 59-74; and

(c) sequence that encode a second gRNA molecule of clams 75-101.

116. The nucleic acid of any of claims 75-103, or 110-112, wherein each of (a), (b), and (c) are present on the same nucleic acid molecule.

117. The nucleic acid of claim 116, wherein said nucleic acid molecule is an AAV vector.

118. The nucleic acid of any of claims 315-103, or 110-112, wherein:

one of (a), (b), and (c) is encoded on a first nucleic acid molecule; and

a second and third of (a), (b), and (c) is encoded on a second nucleic acid molecule.

119. The nucleic acid of claim 118, wherein said first and second nucleic acid

molecules are AAV vectors.

120. The nucleic acid of any of claims 31-103, 108, 109, 111, 112, 118, or 119, wherein: (a) is present on a first nucleic acid molecule; and (b) and (c) are present on a second nucleic acid molecule.

121. The nucleic acid of claim 120, wherein said first and second nucleic acid

molecules are AAV vectors.

122. The nucleic acid of any of claims 31-103, 108-112, 118 or 119, wherein: (b) is present on a first nucleic acid molecule; and (a) and (c) are present on a second nucleic acid molecule.

123. The nucleic acid of claim 122, wherein said first and second nucleic acid

molecules are AAV vectors.

124. The nucleic acid of any of claims 315-103, 106, 107, 113, 114, 118, or 119, wherein: (c) is present on a first nucleic acid molecule; and (b) and (a) are present on a second nucleic acid molecule.

125. The nucleic acid of claim 124, wherein said first and second nucleic acid

molecules are AAV vectors.

126. The nucleic acid of any of claims 108, 113, 118, 120, 122, or 124, wherein said first nucleic acid molecule is other than an AAV vector and said second nucleic acid molecule is an AAV vector.

127. The nucleic acid of any of claims 31-126, wherein said nucleic acid comprises a promoter operably linked to the sequence that encodes said gRNA molecule of (a).

128. The nucleic acid of claims 31-103 or 106-127, wherein said nucleic acid comprises a second promoter operably linked to the sequence that encodes the second gRNA molecule of (c).

129. The nucleic acid of claim 128, wherein the promoter and second promoter differ from one another.

130. The nucleic acid of claim 128, wherein the promoter and second promoter are the same.

131. The nucleic acid of any of claims 31-130, wherein said nucleic acid comprises a promoter operably linked to the sequence that encodes the Cas9 molecule of (b).

132. A composition comprising the (a) gRNA molecule of any of claims 1-30.

133. The composition of claim 132, further comprising (b) a Cas9 molecule of any of claims 59-74.

134. The composition of any of claims 132 or 133, further comprising (c) a second gRNA molecule of any of claims 75-101.

135. The composition of claim 134, further comprising a third gRNA molecule.

136. The composition of claim 135, further comprising a fourth gRNA molecule.

137. The composition of any one of claims 133-136, further comprising (d) a template nucleic acid.

138. A method of altering a cell comprising contacting said cell with:

(a) a gRNA of any of claims 1-30;

(b) a Cas9 molecule of any of claims 59-74;

optionally, (c) a second gRNA molecule of any of claims 75-101; and

optionally, (d) a template nucleic acid.

139. The method of claim 138, further comprising a third gRNA molecule.

140. The method of claim 139, further comprising a fourth gRNA molecule.

141. The method of claim 138, comprising contacting said cell with (a), (b), optionally (c) and optionally (d).

142. The method of any of claims 138-141, wherein said gRNA molecule of (a) is selected from any of claims 1-30.

143. The method of any of claims 138-142, wherein said cell is from a subject

suffering from CF or CF-like disease.

144. The method of any of claims 138-142, wherein said cell is from a subject having a mutation at a CF target position in the CFTR gene or from a subject which would benefit from having a mutation at a CF target position in the SCNNIA gene.

145. The method of any of claims 138-144, wherein said cell is a pulmonary epithelial cell.

146. The method of any of claims 138-144, wherein said cell is a gastrointestinal

epithelial cell, a biliary epithelial cell, or a pancreatic ductal epithelial cell.

147. The method of any of claims 138-144, wherein said cell is a stem cell.

148. The method of any of claims 138-144, wherein said cell is an iPS cell or a cell derived from an iPS cell.

149. The method of claim 138-148, wherein said contacting is performed ex vivo.

150. The method of claim 138-149, wherein said contacted cell is returned to said subject's body.

151. The method of claim 138-148, wherein said contacting is performed in vivo.

152. The method of any of claims 138-151, wherein said cell is from a subject that has CF or CF-like disease.

153. The method of any of claims 138-152, comprising acquiring knowledge of the sequence of the CF target position in said cell.

154. The method of claim 153, comprising acquiring knowledge of the sequence of the CF target position in said cell by sequencing a portion of the CFTR gene or SCNNIA gene.

155. The method of any of claims 138-154, comprising correcting a mutation or

introducing a mutation at the CF target position.

156. The method of any of claims 138-155, wherein contacting comprises contacting said cell with a nucleic acid that encodes at least one of (a), (b), (c) and (d).

157. The method of any of claims 138-156, wherein contacting comprises contacting the cell with a nucleic acid of any of claims 31-131.

158. The method of any of claims 138-157, wherein contacting comprises delivering to said cell said Cas9 molecule of (b) and a nucleic acid which encodes and (a) and optionally (c) and/or (d).

159. The method of any of claims 138-158, wherein contacting comprises delivering to said cell said Cas9 molecule of (b), said gRNA molecule of (a) and optionally said second gRNA molecule of (c).

160. The method of any of claims 138-159, wherein contacting comprises delivering to said cell said gRNA molecule of (a), optionally said second gRNA molecule of (c) and a nucleic acid that encodes the Cas9 molecule of (b).

161. A method of treating a subject, comprising contacting a subject (or a cell from said subject) with:

(a) a gRNA of any of claims 1-30;

(b) a Cas9 molecule of any of claims 59-74;

optionally, (c) a second gRNA of any of claims 75-101; and

optionally, (d) a template nucleic acid.

162. The method of claim 161, further comprising a third gRNA molecule.

163. The method of claim 162, further comprising a fourth gRNA molecule.

164. The method of any one of claims 161-163, further comprising contacting said subject with (a), (b), optionally (c) and optionally (d).

165. The method of claims any one of claims 161-164, wherein said subject is

suffering from CF or CF-like disease.

166. The method of any of claims 161-165, wherein said subject has a mutation at the CF target position in the CFTR gene or would benefit from having a mutation at the CF target position in the SCNNIA gene.

167. The method of any of claims 161-166, comprising acquiring knowledge of the sequence of the CF target position in said subject.

168. The method of claim 167, comprising acquiring knowledge of the sequence of the CF target position in said subject by sequencing a portion of the CFTR gene or SCNNIA gene.

169. The method of claim 161-168, comprising correcting a mutation at the CF target position in the CFTR gene or introducing a mutation at the CF target position in the SCNNIA gene.

170. The method of any of claims 161-169, wherein a cell of said subject is contacted ex vivo with (a), (b), and optionally (c) and/or (d).

171. The method of claim 170, wherein said cell is returned to the subject's body.

172. The method of any of claims 161-169, wherein treatment comprises introducing a cell into said subject's body, wherein said cell subject is contacted ex vivo with (a), (b), and optionally (c) and/or (d).

173. The method of any of claims 161-169, wherein said contacting step is performed in vivo.

174. The method of any of claims 161-169 or 173, wherein said contacting step

comprises inhalation delivery.

175. The method of any of claims 161-169 or 173, wherein said contacting step

comprises intravenous delivery.

176. The method of any of claims 161-169 or 173, wherein said contacting step

comprises intraparenchymal delivery.

177. The method of any of claims 161-169 or 173, wherein said contacting step

comprises intraparenchymal delivery to lung tissue or bronchial tree.

178. The method of any of claims 161-169 or 173-177, comprising contacting said subject or a cell from said subject with a nucleic acid that encodes at least one of (a), (b), and (c).

179. The method of any of claims 161-169 or 173-178, comprising contacting said subject or a cell from said subject with a nucleic acid of any of any of claims 31-103.

180. The method of any of claims 161-179, wherein the contacting step comprises delivering to said subject or a cell from said subject said Cas9 molecule of (b) and a nucleic acid which encodes and (a) and optionally (c), and optionally (d).

181. The method of any of claims 161-180, wherein the contacting step comprises delivering to said subject said Cas9 molecule of (b), said gRNA of (a) and optionally said second gRNA of (c), and optionally said template nucleic acid of (d).

182. The method of any of claims 161-181, wherein the contacting step comprises delivering to said subject said gRNA of (a), optionally said second gRNA of (c) and a nucleic acid that encodes the Cas9 molecule of (b).

183. A reaction mixture comprising a gRNA, a nucleic acid, or a composition

described herein, and a cell from a subject having CF or CF-like disease, a subject having a mutation at a CF target position of the CFTR gene, or a subject which would benefit from having a mutation at a CF target position of the SCNN1A gene.

184. A kit comprising, (a) gRNA molecule of any of claims 1-30, or nucleic acid that encodes said gRNA, and one or more of the following:

(b) a Cas9 molecule of any of claims 59-74;

(c) a second gRNA molecule of any of claims 75-101;

(d) a template nucleic acid; and

(e) nucleic acid that encodes one or more of (b) and (c).

185. The kit of claim 184, comprising nucleic acid that encodes one or more of (a), (b) (c) and (d).

186. The kit of claim 184 or 185, further comprising a third gRNA molecule targeting a CF target mutant position, a CF target knockout position, or a CF target knockdown position.

187. The kit of claim 186, further comprising a fourth gRNA molecule targeting a CF target mutant position, a CF target knockout position, or a CF target knockdown position.

188. A gRNA molecule of any of claims 1-30 for use in treating CF or CF-like disease in a subject.

189. The gRNA molecule of claim 188, wherein the gRNA molecule is used in

combination with (b) a Cas9 molecule of any of claims 59-74.

190. The gRNA molecule of claim 188 or 189, wherein the gRNA molecule is used in combination with (c) a second gRNA molecule of any of claims 75-101.

191. Use of a gRNA molecule of any of claims 1-30, in the manufacture of a

medicament for treating CF or CF-like disease in a subject.

192. The use of claim 191, wherein the medicament further comprises (b) a Cas9

molecule of any of claims 59-74.

193. The use of claim 191 or 192, wherein the medicament further comprises (c) a second gRNA molecule of any of claims 75-101.

194. A composition of any of claims 132-136 for use in treating CF or CF-like disease in a subject.