WO2015148860A1

WO2015148860A1 - Crispr/cas-related methods and compositions for treating beta-thalassemia

Info

Publication number: WO2015148860A1
Application number: PCT/US2015/022851
Authority: WO
Inventors: Ari E. FRIEDLAND; Morgan L. MAEDER; G. Grant Welstead; David A. Bumcrot
Original assignee: Editas Medicine, Inc.
Priority date: 2014-03-26
Filing date: 2015-03-26
Publication date: 2015-10-01

Abstract

CRISPR/CAS-related compositions and methods for treatment of Beta-Thalassemia are disclosed.

Description

CRISPR/CAS-RELATED METHODS AND COMPOSITIONS FOR TREATING BETA-

THALASSEMIA

REFERENCE TO RELATED APPLICATIONS

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

61/970,585, filed March 26, 2014, and U.S. Provisional Application No. 62/084,488, filed November 25, 2014, the contents of each 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 a target nucleic acid sequence, or modulating expression of a target nucleic acid sequence, and applications thereof in connection with Beta- Thalassemia (BT).

BACKGROUND

Beta- thalassemia (BT) is a disease that causes chronic anemia. Beta- thalassemia major (BTM), a more severe form of the disease, is life threatening unless treated with lifelong blood transfusions and iron chelation therapy. Beta- Thalassemia intermedia does not require blood transfusions. However, it may cause growth delay, significant systemic abnormalities and frequently requires lifelong iron chelation therapy.

Beta-thalassemia is caused by mutations in the beta-globin (HBB) gene. HBB is located on chromosome 11 within the HBB gene cluster, which includes genes encoding the delta globin chain, A gamma chain, and G gamma chain. The alpha globin gene is located on chromosome 16. Normal adult hemoglobin (Hb) is composed of a tetramer made from two alpha globin chains and two beta globin chains. In beta-thalassemia, an imbalance of alpha globin and beta globin chains causes anemia. The mutated beta globin chains result in an excess of alpha globin chains that precipitate in erythroid precursors in the bone marrow.

In beta-thalassemia major, both alleles of the beta-globin gene contain a mutation that leads to complete absence of beta globin production (denoted βο/βο). The absence of beta globin chains leads to significant precipitation of alpha globin chains in erythroid cells and severe anemia. Beta-thalassemia major results from nonsense, frameshift or splicing mutations in beta- globin (HBB).

Beta-thalassemia intermedia is due to reduced production of beta globin chains and/or production of mutant beta globin chains. Subject genotypes are denoted βο/ β+ or β+/ β+. βο represents non-expressing beta globin alleles; β+ represents beta globin alleles with reduced expression. Phenotypic expression varies among subjects. As there is some production of beta globin, there is less precipitation of alpha globin chains in the erythroid precursors and less severe anemia than in beta-thalassemia major. However, in beta-thalassemia intermedia there are more significant consequences of erythroid lineage expansion secondary to chronic anemia. Beta-thalassemia intermedia results from mutations in the 5' or 3' untranslated region of HBB, mutations in the promoter region or polyadenylation signal, or from splicing mutations.

Beta-thalassemia affects approximately 1 in 100,000 people worldwide. Its prevalence is higher in certain populations, including those of European descent, where its prevalence is

approximately 1 in 10,000. In the United States, there are approximately 3,000 subjects with beta-thalassemia major.

Subjects with beta-thalassemia major present between the ages of 6 months and 2 years. Subjects suffer from failure to thrive, fevers, hep ato splenomegaly and diarrhea. Adequate treatment includes regular transfusions. Therapy for beta-thalassemia major also includes splenectomy and treatment with hydroxyurea. If subjects are regularly transfused, they will develop normally until the beginning of the second decade. At that time, they require chelation therapy (in addition to continued transfusions) to prevent the complications of iron overload. Iron overload may manifest as growth delay or delay of sexual maturation. In adulthood, inadequate chelation therapy may lead to cardiomyopathy, cardiac arrhythmias, hepatic fibrosis and/or cirrhosis, diabetes, thyroid and parathyroid abnormalities, thrombosis and osteoporosis. Frequent transfusions also put subjects at risk for infection with HIV, hepatitis B and hepatitis C.

Beta-thalassemia intermedia subjects have a variable phenotype. They generally present between the ages of 2-6 years. They do not generally require blood transfusions. However, bone abnormalities occur due to chronic hypertrophy of the erythroid lineage to compensate for chronic anemia. Subjects may have fractures of the long bones due to osteoporosis.

Extramedullary erythropoiesis is common and leads to enlargement of the spleen, liver and lymph nodes. It may also cause spinal cord compression and neurologic problems. Subjects also suffer from lower extremity ulcers and are at increased risk for thrombotic events, including stroke, pulmonary embolism and deep vein thrombosis.

Treatment of beta-thalassemia intermedia includes, e.g., splenectomy, folic acid supplementation, hydroxyurea therapy and radiotherapy for extramedullary masses. Chelation therapy is used in subjects who develop iron overload.

Life expectancy is often diminished in beta-thalassemia subjects. Subjects with beta- thalassemia major who do not receive adequate transfusion therapy generally die in their second or third decade. Subjects with beta-thalassemia major who receive regular transfusions and adequate chelation therapy can live into their 5th decade and beyond. Cardiac failure secondary to iron toxicity is the leading cause of death in beta-thalassemia major subjects due to iron toxicity.

Thus, there remains a need for additional methods and compositions that can be used to treat Beta-thalassemia. SUMMARY OF THE INVENTION

Methods and compositions discussed herein, provide for the treatment or prevention of beta-thalassemia (BT), including Beta-Thalassemia Major (BTM), a severe form of beta- thalassemia, which is characterized by absence of beta globin production. In healthy individuals, the predominant form of hemoglobin (known as HbA) consists of two beta globin molecules paired with two alpha globin molecules and one molecule of heme. The absence of beta globin leads to severe anemia. Elevating levels of fetal hemoglobin (HbF), in which gamma globin substitutes for beta globin, can significantly moderate the severe anemia of BT. However, the expression of gamma globin is negatively regulated by the BCL11A gene product.

Methods and compositions discussed herein, allow for the treatment or prevention of BT, or its symptoms, e.g., by altering the gene for B-cell CLL/lymphoma 11A (BCL11A). The

BCL11A gene is also known as B-cell CLL/lymphoma 11 A, BCL11A-L, BCL11A-S, BCL11A- XL, CTIP1, HBFQTL5 and ZNF. BCL11A encodes a zinc-finger protein that is involved in the regulation of globin gene expression. By altering the BCL11A gene (e.g., one or both alleles of the BCL11A gene), the levels of gamma globin can be increased. Gamma globin can replace beta globin in the hemoglobin complex and effectively carry oxygen to tissues, thereby ameliorating BT disease phenotypes. In one aspect, methods and compositions discussed herein may be used to alter the BCLllA gene to treat or prevent BT, by targeting the BCLllA gene, e.g., coding or non-coding regions of the BCLllA gene. Altering the BCLllA gene herein refers to reducing or eliminating (1) BCLllA gene expression, (2) BCL11A protein function, or (3) the level of BCL11A protein.

In an embodiment, the coding region (e.g., an early coding region) of the BCLllA gene is targeted for alteration. In an embodiment, a non-coding sequence (e.g., an enhancer region, a promoter region, an intron, 5'UTR, 3'UTR, or polyadenylation signal) is targeted for alteration.

In an embodiment, the method provides an alteration that comprises disrupting the BCLllA gene by the insertion or deletion of one or more nucleotides mediated by a Cas9 molecule (e.g., an enzymatically active Cas9 (eaCas9) molecule, e.g., Cas9 nuclease or Cas9 nickase) as described below. This type of alteration is also referred to as "knocking out" the BCLllA gene. While not wishing to be bound by theory, in an embodiment, a targeted knockout approach is mediated by NHEJ using a CRISPR/Cas system comprising a Cas9 molecule, e.g., an enzymatically active Cas9 (eaCas9) molecule.

In another embodiment, the method provides an alteration that does not comprise nucleotide insertion or deletion in the BCLllA gene and is mediated by an enzymatically inactive Cas9 (eiCas9) molecule or an eiCas9-fusion protein, as described below. This type of alteration is also referred to as "knocking down" the BCLllA gene. While not wishing to be bound by theory, in an embodiment, a targeted knockdown approach is mediated by NHEJ using a CRISPR/Cas system comprising a Cas9 molecule, e.g., an enzymatically inactive Cas9

(eiCas9) molecule.

In an embodiment, the methods and compositions discussed herein may be used to alter the BCLllA gene to treat or prevent BT by knocking out one or both alleles of the BCLllA gene. In an embodiment, the coding region (e.g., an early coding region) of the BCLllA gene, is targeted to alter the gene. In an embodiment, a non-coding region of the BCLllA gene (e.g., an enhancer region, a promoter region, an intron, 5' UTR, 3'UTR, polyadenylation signal) is targeted to alter the gene. In an embodiment, an enhancer (e.g., a tissue-specific enhancer, e.g., a myeloid enhancer, e.g., an erythroid enhancer) is targeted to alter the gene.

BCLllA erythroid enhancer comprises an approximatel2.4 kb fragment of BCLllA intron 2, located between approximate +52.0 to +64.4 kilobases (kb) from the Transcription Start Site (TSS+52kb to TSS+64.4kb, see Fig. 10). It is also referred to herein as chromosome 2 location 60,716,189-60,728,612 (according to UCSC Genome Browser hg 19 human genome assembly). Three deoxyribonuclese I hypersensitive sites (DHSs), TSS+62kb, TSS+58kb and TSS+55kb are located in this region. Deoxyribonuclease I sensitivity is a marker for gene regulatory elements. While not wishing to be bound by theory, it is believed that deleting the enhancer region (e.g., TSS+52kb to TSS+64.4kb) may reduce or eliminate BCLllA expression in erythroid precursors which leads to gamma globin derepression while sparing BCLllA expression in nonerythoroid lineages.

In an embodiment, the method provides an alteration that comprises a deletion of the enhancer region (e.g., a tissue-specific enhancer, e.g., a myleloid enhancer, e.g., an erythroid enhancer) or a protion of the region resulting in disruption of one or more DNase 1- hypersensitivie sites (DHS). In an embodiment, the method provides an alteration that comprises an insertion or deletion of one or more nucleotides.

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) molecule. In an embodiment, a targeted knockout approach alters the BCLllA gene. In an embodiment, a targeted knockout approach reduces or eliminates expression of functional BCLllA gene product. In an embodiment, targeting affects one or both alleles of the BCLllA gene. In an embodiment, an enhancer disruption approach reduces or eliminates expression of functional BCLllA gene product in the erythroid lineage.

"BT target knockout position", as used herein, refers to a position in the BCLllA gene, which if altered, e.g., disrupted by insertion or deletion of one or more nucleotides, e.g., by NHEJ-mediated alteration, results in alteration of the BCLllA gene. In an embodiment, the position is in the BCLllA coding region, e.g., an early coding region. In an embodiment, the position is in a BCLllA non-coding region, e.g., an enhancer region.

In an embodiment, methods and compositions discussed herein, provide for altering (e.g., knocking out) the BCLllA gene. In an embodiment, knocking out the BCLllA gene herein refers to (1) insertion 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 BCLllA gene, or (2) deletion (e.g., NHEJ-mediated deletion) of genomic sequence including the erythroid enhancer of the BCLllA gene. Both approaches give rise to alteration of the BCLllA gene as described above. In an embodiment, the BT target knockout position is altered by genome editing using the CRISPR/Cas9 system. The BT target knockout position may be targeted by cleaving with either a single nuclease or dual nickases, e.g., to induce insertion 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 BT target knockout position or to delete (e.g., mediated by NHEJ) a genomic sequence including the erythroid enhancer of the BCLllA gene.

In an embodiment, the methods and compositions described herein introduce one or more breaks in close proximity to or within the early coding region in at least one allele of the BCLllA gene. In an embodiment, a single strand break is introduced in close proximity to or within the early coding region in at least one allele of the BCLllA gene. In an embodiment, the single strand break will be accompanied by an additional single strand break, positioned by a second gRNA molecule.

In an embodiment, a double strand break is introduced in close proximity to or within the early coding region in at least one allele of the BCLllA gene. In an embodiment, a double strand break will be accompanied by an additional single strand break positioned by a second gRNA molecule. In an embodiment, a double strand break will be accompanied by two additional single strand breaks positioned by a second gRNA molecule and a third gRNA molecule.

In an embodiment, a pair of single strand breaks is introduced in close proximity to or within the early coding region in at least one allele of the BCLllA gene. In an embodiment, the pair of single strand breaks will be accompanied by an additional double strand break, positioned by a third gRNA molecule. In an embodiment, the pair of single strand breaks will be accompanied by an additional pair of single strand breaks positioned by a third gRNA molecule and a fourth gRNA molecule.

In an embodiment, two double strand breaks are introduced to flank the erythroid enhancer of the BCLllA gene (one 5' and the other one 3' to the erythroid enhancer) to remove (e.g., delete) the genomic sequence including the erythroid enhancer. Without wishing to be bound by theory, it is contemplated herein that in an embodiment the deletion of the genomic sequence including the erythroid enhancer is mediated by NHEJ. In an embodiment, the breaks (i.e., the two double strand breaks) are positioned to avoid unwanted deletion of certain elements, such as endogenous splice sites. The breaks, i.e., two double strand breaks, can be positioned upstream and downstream of the erythroid enhancer, as discussed herein. In an embodiment, two sets of breaks (e.g., one double strand break and a pair of single strand breaks) are introduced to flank the erythroid enhancer in the BCL11A gene (one set 5' and the other set 3' to the erythroid enhancer) to remove (e.g., delete) the genomic sequence including the erythroid enhancer. Without wishing to be bound by theory, it is contemplated herein that in an embodiment the deletion of the genomic sequence including the erythroid enhancer is mediated by NHEJ. In an embodiment, the breaks (i.e., the double strand break and the pair of single strand breaks) are positioned to avoid unwanted deletion of certain

chromosome elements, such as endogenous splice sites. The breaks, e.g., the double strand break and the pair of single strand breaks, can be positioned upstream and downstream of the erythroid enhancer, as discussed herein.

In an embodiment, two sets of breaks (e.g., two pairs of single strand breaks) are introduced to flank the erythroid enhancer at the BT target position in the BCL11A gene (one set 5' and the other set 3' to the erythroid enhancer) to remove (e.g., delete) the genomic sequence including the erythroid enhancer. Without wishing to be bound by theory, it is contemplated herein that in an embodiment the deletion of the genomic sequence including the erythroid enhancer is mediated by NHEJ. In an embodiment, the breaks (i.e., the two pairs of single strand breaks) are positioned to avoid unwanted deletion of certain chromosome elements, such as endogenous splice sites. The breaks, e.g., the two pairs of single strand breaks, can be positioned upstream and downstream of the erythroid enhancer, as discussed herein.

In an embodiment, the methods and compositions discussed herein may be used to alter the BCL11A gene to treat or prevent BT by knocking down one or both alleles of the BCL11A gene. In one embodiment, the coding region of the BCL11A gene, is targeted to alter the gene. In another embodiment, a non-coding region (e.g., an enhancer region, a promoter region, an intron, 5' UTR, 3'UTR, polyadenylation signal) of the BCL11A gene is targeted to alter the gene. In an embodiment, the promoter region of the BCL11A gene is targeted to knock down the expression of the BCL11A gene. A targeted knockdown approach alters, e.g., reduces or eliminates the expression of the BCL11A gene. As described herein, in an embodiment, a targeted knockdown is mediated by targeting 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) to alter transcription, e.g., to block, reduce, or decrease

transcription, of the BCL11A gene. "BT target knockdown position", as used herein, refers to a position, e.g., in the BCL11A gene, which if targeted by an eiCas9 or an eiCas9 fusion described herein, results in reduction or elimination of expression of functional BCL11A gene product. In an embodiment, transcription is reduced or eliminated. In an embodiment, the position is in the BCL11A promoter sequence, In an embodiment, a position in the promoter sequence of the BCL11A gene is targeted by an enzymatically inactive Cas9 (eiCas9) molecule or an eiCas9 fusion protein, as described herein.

In an embodiment, one or more gRNA molecule comprising a targeting domain 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 BT target knockdown position to reduce, decrease or repress expression of the BCL11A gene.

"BT target position", as used herein, refers to any of a BT target knockout position, or BT target knockdown position.

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 BCL11A gene.

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 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 in an embodiment 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 an embodiment, 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 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., an Alu repeat, or the endogenous 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 another embodiment, a position in the coding region, e.g., the early coding region, of the BCL11A 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 1A-1F, 3A-3E, 4A-4E, 5A-5B, 12A-12D, 13A-13E, or 14A-14B. In an embodiment, the targeting domain is independently selected from those in Tables 1A-1F, 3A-3E, 4A-4E, 5A-5B, 12A-12D, 13A-13E, or 14A-14B.

In another embodiment, a position in the coding region, e.g., the early coding region, of the BCL11A 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 1A-1F. In an embodiment, the targeting domain is independently selected from those in Tables 1A-1F. In an embodiment, the targeting domain is independently selected from:

UGGCAUCCAGGUCACGCCAG (SEQ ID NO: 387);

GAUGCUUUUUUCAUCUCGAU (SEQ ID NO: 388);

GCAUCCAAUCCCGUGGAGGU (SEQ ID NO: 389);

UUUUCAUCUCGAUUGGUGAA (SEQ ID NO: 390);

CCAGAUGAACUUCCCAUUGG (SEQ ID NO: 391);

AGGAGGUCAUGAUCCCCUUC (SEQ ID NO: 392);

CAUCCAGGUCACGCCAG (SEQ ID NO: 393);

GCUUUUUUCAUCUCGAU (SEQ ID NO: 394);

UCCAAUCCCGUGGAGGU (SEQ ID NO: 395); UCAUCUCGAUUGGUGAA (SEQ ID NO: 396);

GAUGAACUUCCCAUUGG (SEQ ID NO: 397); or

AGGUCAUGAUCCCCUUC (SEQ ID NO: 398).

In an embodiment, when the BT target knockout position is the BCL11A coding region, e.g., early coding region, and more than one gRNA is used to position breaks, e.g., two single strand breaks or two double strand 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 selected from one of Tables 1A-1F.

In another embodiment, a position in the coding region, e.g., the early coding region, of the BCL11A 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-3E. In an embodiment, the targeting domain is independently selected from those in Tables 3A-3E. In another

embodiment, the targeting domain is independently selected from:

GAGCTCCATGTGCAGAACGA (SEQ ID NO: 2574);

GAGCTCCCAACGGGCCG (SEQ ID NO: 2575);

GAGTGCAGAATATGCCCCGC (SEQ ID NO: 2576);

GATAAACAATCGTCATCCTC (SEQ ID NO: 2577);

GATGCCAACCTCCACGGGAT (SEQ ID NO: 2578);

GCAGAATATGCCCCGCA (SEQ ID NO: 2579);

GCATCCAATCCCGTGGAGGT (SEQ ID NO: 2580);

GCCAACCTCCACGGGAT (SEQ ID NO: 2581);

GCTCCCAACGGGCCGTGGTC (SEQ ID NO: 2582); or

GGAGCTCTAATCCCCACGCC (SEQ ID NO: 2583).

In another embodiment, a position in the coding region, e.g., the early coding region, of the BCL11A 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 4A-4E. In an embodiment, the targeting domain is independently selected from those in Tables 4A-4E.

In another embodiment, a position in the coding region, e.g., the early coding region, of the BCL11A 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 5A-5B. In an embodiment, the targeting domain is independently selected from those in Tables 5A-5B. In another embodiment, a position in the coding region, e.g., the early coding region, of the BCL11A 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 12A-12D. In an embodiment, the targeting domain is independently selected from those in Tables 12A-12D.

In another embodiment, a position in the coding region, e.g., the early coding region, of the BCL11A 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 13A-13E. In an embodiment, the targeting domain is independently selected from those in Tables 13A-13E.

In another embodiment, a position in the coding region, e.g., the early coding region, of the BCL11A 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 14A-14B. In an embodiment, the targeting domain is independently selected from those in Tables 14A-14B.

In an embodiment, when the BT target knockout position is the BCL11A coding region, e.g., early coding region, and more than one gRNA is used to position breaks, e.g., two single strand breaks or two double strand 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 comprises a targeting domain that is selected from any one of Tables 1A-1F, 3A-3E, 4A-4E, 5A-5B, 12A-12D, 13A-13E, or 14A-14B.

In another embodiment, a position in the non-coding region, e.g., the enhancer region, of the BCL11A 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 6A-6D, 7A-7D, 8, 18A-18E, 19A- 19E, or 20A-20C. In an embodiment, the targeting domain is independently selected from those in Tables 6A-6D, 7A-7D, 8, 18A-18E, 19A-19E, or 20A-20C.

In another embodiment, a position in the non-coding region, e.g., the enhancer region, of the BCL11A 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 6A-6D. In an embodiment, the targeting domain is independently selected from those in Tables 6A-6D. In another embodiment, the targeting domain is independently selected from:

GAAAATACTTACTGTACTGC (SEQ ID NO: 4336);

GAAAGCAGTGTAAGGCT (SEQ ID NO: 4337);

GGCTGTTTTGGAATGTAGAG (SEQ ID NO: 4338); or

GTGCTACTTATACAATTCAC (SEQ ID NO: 4339).

In an embodiment, a position in the non-coding region, e.g., the enhancer region, of the BCLllA 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 7A-7D. In an embodiment, the targeting domain is independently selected from those in Tables 7A-7D.

In an embodiment, a position in the non-coding region, e.g., the enhancer region, of the BCLllA 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 Table 8. In an embodiment, the targeting domain is independently selected from those in Table 8.

In an embodiment, a position in the non-coding region, e.g., the enhancer region, of the BCLllA 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 18A-18E. In an embodiment, the targeting domain is independently selected from those in Tables 18A-18E.

In an embodiment, a position in the non-coding region, e.g., the enhancer region, of the BCLllA 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 19A-19E. In an embodiment, the targeting domain is independently selected from those in Tables 19A-19E.

In an embodiment, a position in the non-coding region, e.g., the enhancer region, of the BCLllA 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 20A-20C. In an embodiment, the targeting domain is independently selected from those in Tables 20A-20C. In an embodiment, when the BT target knockout position is in the non-coding region, e.g., the enhancer region, and more than one gRNA is used to position breaks, e.g., two single strand breaks or two double strand breaks, or a combination of single strand and double strand breaks, e.g., to create one or more deletions, in the target nucleic acid sequence, each guide RNA comprises a targeting domain that is selected from any one of Tables 6A-6D, 7A-7D, 8, 18A- 18E, 19A-19E, or 20A-20C.

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 the BCL11A transcription start site (TSS) to reduce (e.g., block) transcription initiation, 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, or between 500 bp upstream and 500 bp downstream) of the TSS of the BCL11A gene. One or more gRNA may be used to target an eiCas9 to the promoter region of the BCL11A gene.

In an embodiment, 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 2A-2C, 9A-9D, 10A-10D, 11, 15A-15C, 16A-16E, or 17A-17C. In an

embodiment, the targeting domain is independently selected from those in Tables 2A-2C, 9A- 9D, 10A-10D, 11, 15A-15C, 16A-16E, or 17A-17C.

In an embodiment, when the BCL11A 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 2A-2C. In an embodiment, the targeting domain is independently selected from those in Tables 2A-2C.

In an embodiment, when the BCL11A 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 9A-9D. In an embodiment, the targeting domain is independently selected from those in Tables 9A-9D. In another embodiment, the targeting domain is independently selected from:

GACGACGGCTCGGTTCACAT (SEQ ID NO: 4482);

GACGCCAGACGCGGCCCCCG (SEQ ID NO: 4483);

GCCTTGCTTGCGGCGAGACA (SEQ ID NO: 4484); GGCTCCGCGGACGCCAGACG (SEQ ID NO: 4485);

GACGGCTCGGTTCACAT (SEQ ID NO: 4486);

GCCGCGTCTGGCGTCCG (SEQ ID NO: 4487); or

GCGGGCGGACGACGGCT (SEQ ID NO: 4488).

In an embodiment, when the BCL11A 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 10A-10D. In an embodiment, the targeting domain is independently selected from those in Tables 10A-10D.

In an embodiment, when the BCL11A 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 Table 11. In an embodiment, the targeting domain is independently selected from those in Table 11.

In an embodiment, when the BCL11A 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 15A-15C. In an embodiment, the targeting domain is independently selected from those in Tables 15A-15C.

In an embodiment, when the BCL11A 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 16A-16E. In an embodiment, the targeting domain is independently selected from those in Tables 16A-16E.

In an embodiment, when the BCL11A 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 17A-17C. In an embodiment, the targeting domain is independently selected from those in Tables 17A-17C.

In an embodiment, the BT target knockdown position is the BCL11A promoter region. In an embodiment, 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, each guide RNA comprises a targeting domain that is selected from any one of Tables 2A-2C, 9A-9D, 10A-10D, 11, 15A-15C, 16A-16E, 17A-17C.

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 described herein, e.g., selected from any one of Tables 1A-1F, 2A-2C, 3A-3E, 4A-4E, 5A-5B, 6A-6D, 7A-7D, 8, 9A-9D, 10A-10D, 11, 12A-12D, 13A-13E, 14A-14B, 15A-15C, 16A-16E, 17A-17C, 18A-18E, 19A-19E, 20A-20C, or 31. In an embodiment, the targeting domain is selected from those in Tables 1A-1F, 2A-2C, 3A-3E, 4A-4E, 5A-5B, 6A-6D, 7A-7D, 8, 9A-9D, 10A-10D, 11, 12A-12D, 13A-13E, 14A-14B, 15A-15C, 16A-16E, 17A-17C, 18A-18E, 19A-19E, 20A-20C, or 31.

In an embodiment, the targeting domain which is complementary with a target domain in the BCLllA gene (e.g., a target domain from a BT target position in the BCLllA 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.

In an embodiment, the targeting domain comprises 26 nucleotides.

In an embodiment, the gRNA, e.g., a gRNA comprising a targeting domain, which is complementary with a target domain in the BCLllA gene (e.g., a target domain from a BT target position in the BCL11A gene), is a modular gRNA. In another embodiment, the gRNA is a unimolecular or chimeric gRNA.

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 an embodiment, 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 greater than 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or 26 nucleotides 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 25 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 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 greater than 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or 26 nucleotides 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 greater than 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or 26 nucleotides 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). Alternatively, in an embodiment, the Cas9 molecule may be 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.

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 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 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 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., N863A.

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 BT target position, in the BCL11A 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 BT target position in the BCL11A gene to allow alteration, e.g., alteration associated with NHEJ, of a BT target position in the BCL11A 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 fusion protein (e.g., an eiCas9 fused to a transcription repressor domain), sufficiently close to a BT knockdown target position to reduce, decrease or repress expression of the BCL11A 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 from any one of Tables 1A-1F, 2A-2C, 3A-3E, 4A-4E, 5A-5B, 6A-6D, 7A-7D, 8, 9A-9D, 10A-10D, 11, 12A- 12D, 13A-13E, 14A-14B, 15A-15C, 16A-16E, 17A-17C, 18A-18E, 19A-19E, 20A-20C, or 31.

In an embodiment, the nucleic acid encodes a gRNA molecule comprising a targeting domain is selected from those in Tables 1A-1F, 2A-2C, 3A-3E, 4A-4E, 5A-5B, 6A-6D, 7A-7D, 8, 9A-9D, 10A-10D, 11, 12A-12D, 13A-13E, 14A-14B, 15A-15C, 16A-16E, 17A-17C, 18A-18E, 19A- 19E, 20A-20C, or 31.

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 still 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.

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 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 an embodiment, 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 25 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 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.

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 BCL11A gene as disclosed herein, and further comprising (b) a sequence that encodes 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 that forms a single strand break in a target nucleic acid (e.g., a nickase molecule). 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., N863A.

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 BCL11A gene as disclosed herein; (b) a sequence that encodes a Cas9 molecule.

Alternatively, in an embodiment, the Cas9 molecule may be 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 BCL11A gene as disclosed herein; (b) a sequence that encodes a Cas9 molecule; and further maycomprise (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 BCL11A 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 BCLllA 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 BCLllA 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 BT target position in the BCLllA gene, to allow alteration, e.g., alteration associated with NHEJ, of a BT target position in the BCLllA gene, either alone or in combination with the break positioned by said first gRNA molecule.

In an embodiment, the nucleic acid encodes a second gRNA molecule comprising a targeting domain 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 BT knockdown target position to reduce, decrease or repress expression of the

BCLllA 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 BT target position in the BCLllA gene to allow alteration, e.g., alteration associated with NHEJ, of a BT target position in the BCLllA gene, either alone or in combination with the break positioned by the first and/or second gRNA molecule.

In an embodiment, the nucleic acid encodes a third gRNA molecule comprising a targeting domain 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 BT knockdown target position to reduce, decrease or repress expression of the

BCLllA 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 BT target position in the BCLllA gene to allow alteration, e.g., alteration associated with NHEJ, of a BT target position in the BCLllA 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 fourth gRNA molecule comprising a targeting domain 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 BT knockdown target position to reduce, decrease or repress expression of the BCL11A gene.

In an embodiment, the nucleic acid encodes a second gRNA molecule. The second gRNA is selected to target the same BT 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 BT 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-1F, 2A-2C, 3A-3E, 4A-4E, 5A-5B, 6A-6D, 7A-7D, 8, 9A-9D, 10A-10D, 11, 12A-12D, 13A-13E, 14A-14B, 15A- 15C, 16A-16E, 17A-17C, 18A-18E, 19A-19E, 20A-20C, or 31. In an embodiment, the nucleic acid encodes a second gRNA molecule comprising a targeting domain selected from those in Tables 1A-1F, 2A-2C, 3A-3E, 4A-4E, 5A-5B, 6A-6D, 7A-7D, 8, 9A-9D, 10A-10D, 11, 12A- 12D, 13A-13E, 14A-14B, 15A-15C, 16A-16E, 17A-17C, 18A-18E, 19A-19E, 20A-20C, or 31. 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-1F, 2A-2C, 3A-3E, 4A-4E, 5A-5B, 6A-6D, 7A-7D, 8, 9A-9D, 10A-10D, 11, 12A-12D, 13A-13E, 14A-14B, 15A-15C, 16A-16E, 17A-17C, 18A-18E, 19A- 19E, 20A-20C, or 31. 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-1F, 2A-2C, 3A-3E, 4A-4E, 5A-5B, 6A-6D, 7A-7D, 8, 9A-9D, 10A-10D, 11, 12A-12D, 13A-13E, 14A-14B, 15A-15C, 16A-16E, 17A-17C, 18A-18E, 19A- 19E, 20A-20C, or 31.

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 another embodiment, the nucleic acid encodes a second gRNA comprising a targeting domain that is 17 nucleotides in length. In still 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 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 a fourth gRNA, each 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 an embodiment, 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 than 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or 26 nucleotides 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 than 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or 26 nucleotides 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 than 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or 26 nucleotides 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 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.

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 BCL11A 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 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, 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 BCL11A gene as disclosed herein, and (b) a sequence that encodes a Cas9 molecule, e.g., a Cas9 molecule described herein; andfurther comprises (c)(i) a sequence that encodes a second gRNA molecule as described herein 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 BCL11A 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 BCL11A gene. In an embodiment, the nucleic acid comprises (a), (b) and (c)(i). In an embodiment, the nucleic acid comprises (a), (b), (c)(i) and (c)(ii). In an embodiment, the nucleic acid comprises (a), (b), (c)(i), (c)(ii) and (c)(iii). 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.

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.

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 an embodiment, 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 BCLllA 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. 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 BT 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 BCLllA 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 BCLllA gene, e.g., a gRNA, 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).

The targeting domain of the gRNA of (a) and optionally (c) may be selected from any of Tables 1A-1F, 2A-2C, 3A-3E, 4A-4E, 5A-5B, 6A-6D, 7A-7D, 8, 9A-9D, 10A-10D, 11, 12A- 12D, 13A-13E, 14A-14B, 15A-15C, 16A-16E, 17A-17C, 18A-18E, 19A-19E, 20A-20C, or 31, or a targeting domain of 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-1F, 2A-2C, 3A-3E, 4A-4E, 5A-5B, 6A-6D, 7A-7D, 8, 9A-9D, 10A-10D, 11, 12A-12D, 13A-13E, 14A-14B, 15A-15C, 16A-16E, 17A-17C, 18A-18E, 19A-19E, 20A-20C, or 31.

In an embodiment, the method comprises contacting a cell from a subject suffering from or likely to develop BT. The cell may be from a subject that would benefit from having a mutation at a BT target position.

In an embodiment, the cell being contacted in the disclosed method is an erythroid 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 another embodiment, 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 of a BT target position in said cell, prior to the contacting step.

Acquiring knowledge of the sequence of a BT target position in the cell may be by sequencing the BCL11A gene, or a portion of the BCL11A 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 (a) and optionally, a second gRNA (c)(i) (and further optionally, a third gRNA (c)(iv) 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), 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 (a), and optionally, a second gRNA (c)(i) (and further optionally, a third gRNA (c)(iv) 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 said 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 a subject suffering from or likely to develop BT, 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 BCLllA 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 BCLllA 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 BCL11 A gene, e.g., a third and fourth gRNA disclosed herein.

In an embodiment, contacting comprises contacting with (a) and (b).

In an embodiment, contacting comprises contacting with (a), (b), and (c)(i).

In an embodiment, contacting comprises contacting with (a), (b), (c)(i) and (c)(ii).

In an embodiment, contacting comprises contacting with (a), (b), (c)(i), (c)(ii) and (c)(iii).

The targeting domain of the gRNA of (a) or (c) (e.g., (c)(i), (c)(ii), or (c)(iii) may be selected from any of Tables 1A-1F, 2A-2C, 3A-3E, 4A-4E, 5A-5B, 6A-6D, 7A-7D, 8, 9A-9D, 10A-10D, 11, 12A-12D, 13A-13E, 14A-14B, 15A-15C, 16A-16E, 17A-17C, 18A-18E, 19A- 19E, 20A-20C, or 31, or a targeting domain of 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-1F, 2A-2C, 3A-3E, 4A- 4E, 5A-5B, 6A-6D, 7A-7D, 8, 9A-9D, 10A-10D, 11, 12A-12D, 13A-13E, 14A-14B, 15A-15C, 16A-16E, 17A-17C, 18A-18E, 19A-19E, 20A-20C, or 31.

In an embodiment, the method comprises acquiring knowledge of the sequence at a BT target position in said subject.

In an embodiment, the method comprises acquiring knowledge of the sequence at a BT target position in said subject by sequencing the BCLllA gene or a portion of the BCLllA gene.

In an embodiment, the method comprises introducing a mutation at a BT target position.

In an embodiment, the method comprises introducing a mutation at a BT target position by NHEJ.

When the method comprises introducing a mutation at a BT target position, e.g., by NHEJ in the coding region or a non-coding 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 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).

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).

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), 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), 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, and optionally said second gRNA of (c)(i), and 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, and a nucleic acid that encodes the Cas9 molecule of (b).

When the method comprises (1) introducing a mutation at a BT target position by NHEJ or (2) knocking down expression of the BCL11A gene, e.g., 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 another aspect, disclosed herein is a cell or a plurality of cells produced (e.g., altered) by a method described herein.

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 BT, or a subject which would benefit from a mutation at a BT target position. In another aspect, disclosed herein is a kit comprising, (a) a gRNA molecule described herein, or a 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).

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), and (c)(iii).

In an embodiment, the kit further comprises a governing gRNA molecule, or a nucleic acid that encodes a governing gRNA molecule.

In an aspect, the disclosure features a gRNA molecule, referred to herein as a governing 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. 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, it is believed that altering, e.g., inactivating, a nucleic acid that encodes a Cas9 molecule or a 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 gRNA molecules and methods, as disclosed herein, can be used in combination with a governing gRNA molecule. The compositions and reaction mixtures, as disclosed herein, can also include a governing gRNA molecule, e.g., a governing gRNA molecule disclosed herein.

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

In an embodiment, the gRNA molecule is 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 BT in a subject, e.g., in accordance with a method of treating preventing BT 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.

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);

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, 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.

Fig. 10 shows chromosome 2 location (according to UCSC Genome Browser hg 19 human genome assembly) that corresponds to BCLl 1 A intron 2. Three erythroid DHSs are labled as distance in kilobases from BCLl 1A TSS (+62, +58 and +55). BCLl 1A transcription is from right to left.

Fig. 11 depicts the efficiency of NHEJ mediated by a Cas9 molecule and exemplary gRNA molecules targeting three different regions of the BCLl 1 A locus.

Figs. 12A-12B depict detected deletion events resulting from co-transfection of exemplary gRNA molecules, BCLl 1A-2983W and BCLl 1A-2981W.

Fig. 12A depicts schematic of DNA sequence recognized by BCLl 1 A-2983W and BCLl 1A-2981W, which flanks the putative erythroid enhancer elements.

Fig. 12B depicts sequenced deletion events from the TOPO cloning of the PCR using primers that flank the enhancer region. A product is obtained when a deletion event has taken place.

Figs. 13A-13B depict detected deletion events resulting from co-transfection of the exemplary gRNA molecules, BCL11A-2995W and BCL11A-2984W.

Fig. 13A depicts schematic of DNA sequence recognized by BCLl 1 A-2995W and BCLl 1 A-2984W, which flanks the putative erythroid enhancer elements.

Fig. 13B depicts sequenced deletion events from the TOPO cloning of the PCR using primers that flank the enhancer region. A product is obtained when a deletion event has taken place.

DETAILED DESCRIPTION

Definitions

"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 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 BCLllA 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, 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 BCLllA 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 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.

A "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.

"Non-homologous end joining" or "NHEJ", as used herein, refers to ligation mediated repair and/or non-template mediated repair including, e.g., canonical NHEJ (cNHEJ), alternative NHEJ (altNHEJ), microhomology-mediated end joining (MMEJ), single-strand annealing (SSA), and synthesis-dependent microhomology-mediated end joining (SD-MMEJ).

"A 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 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 another embodiment, 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.

"Prevent", "preventing" and "prevention", as used herein, means the prevention of a disease in a mammal, e.g., in a human, including (a) avoiding or precluding the disease; (2) affecting the predisposition toward the disease, e.g., preventing at least one symptom of the disease or to delay onset of at least one symptom of 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.

Methods of Altering BCL11A

One approach to increase the expression of HbF involves identification of genes whose products play a role in the regulation of globin gene expression. One such gene is BCL11A. It plays a role in the regulation of γ globin expression. It was first identified because of its role in lymphocyte development. BCL11A encodes a zinc finger protein that is thought to be involved in the stage specific regulation of γ globin expression. BCLl 1 A is expressed in adult erythroid precursor cells and down-regulation of its expression leads to an increase in γ globin expression. In addition, it appears that the splicing of the BCLl 1 A mRNA is developmentally regulated. In embryonic cells, it appears that the shorter BCLl 1 A mRNA variants, known as BCLl 1 A-S and BCLl 1A-XS are primary expressed, while in adult cells, the longer BCLl 1 A-L and BCLl 1A- XL mRNA variants are predominantly expressed. See, Sankaran et al. (2008) Science 322 p. 1839. The BCLl 1A protein appears to interact with the β globin locus to alter its conformation and thus its expression at different developmental stages. Thus, if BCLl 1 A expression is altered e.g., disrupted (e.g., reduced or eliminated), it results in the elevation of γ globin and HbF production.

Disclosed herein are methods for altering the BT target position in the BCLllA gene. Altering the BT target position is achieved, e.g., by:

(1) knocking out the BCLllA gene:

(a) insertion 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 BCLllA gene, or

(b) deletion (e.g., NHEJ-mediated deletion) of genomic sequence including the erythroid enhancer of the BCLllA gene, or

(2) knocking down the BCLllA gene mediated by enzymatically inactive Cas9 (eiCas9) molecule or an eiCas9-fusion protein by targeting the promoter region of the gene.

All approaches give rise to alteration of the BCLllA gene. In one embodiment, methods described herein introduce one or more breaks near the early coding region in at least one allele of the BCLllA gene. In another embodiment, methods described herein introduce two or more breaks to flank the erythroid enhancer of BT target knockout position. The two or more breaks remove (e.g., delete) genomic sequence including the erythorid enhancer. In another

embodiment, methods described herein comprises knocking down the BCLllA gene mediated by enzymatically inactive Cas9 (eiCas9) molecule or an eiCas9-fusion protein by targeting the promoter region of BT target knockdown position. All methods described herein result in alteration of the BCLllA gene. NHEJ-mediated introduction of an indel in close proximity to or within the early coding region of the BT knockout position

In an embodiment, the method comprises introducing a NHEJ-mediated insertion or deletion of one more nucleotides in close proximity to the BT target knockout position (e.g., the early coding region) of the BCL11A 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 BT target knockout position, such that the break-induced indel could be reasonably expected to span the BT target knockout position (e.g., the early coding region). 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 BT target knockout position.

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 the early coding region in the BCL11A gene to allow alteration, e.g., alteration associated with NHEJ in the BCL11A 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 a BT target knockout position. The break, e.g., a double strand or single strand break, can be positioned upstream or downstream of a BT target knockout position in the BCL11A 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 early coding region in the BCL11A gene, to allow alteration, e.g., alteration associated with NHEJ in the BCL11A 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, 250, 300, 350, 400, 450 or 500 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 BT target knockout position in the BCL11A 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 BT target knockout position in the BCLllA 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, 250, 300, 350, 400, 450 or 500 nucleotides of the early coding region in the BCLllA gene. 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 alteration of the early coding region in the BCLllA gene in the BCLllA 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 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 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 early coding region in the BCLllA 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, 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 of the early coding region in the BCLllA gene in the BCLllA 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, 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 early coding region in the BCLllA 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, 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 early coding region in the BCL11A 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, 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 early coding region in the BCL11A 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, 250, 300, 350, 400, 450 or 500 nucleotides of the early coding region in the BCL11A gene; and the targeting domains of a third and fourth gRNA molecule are configured such that two single strand breaks are positioned downstream of a BT target knockout position in the BCL11A gene the early coding region in the BCL11A 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, 250, 300, 350, 400, 450 or 500 nucleotides of the early coding region in the BCL11A gene. NHEJ-mediated deletion of the erythroid enhancer at the BT target position

In an embodiment, the method comprises introducing a NHEJ-mediated deletion of a genomic sequence including the erythroid enhancer. As described herein, in one embodiment, the method comprises the introduction of two double strand breaks— one 5' and the other 3' to (i.e., flanking) the BT target position (e.g., the erythroid enhancer). Two gRNAs, e.g., unimolecular (or chimeric) or modular gRNA molecules, are configured to position the two double strand breaks on opposite sides of the BT target knockdown position (e.g., the erythroid enhancer) in the BCL11A gene. In an embodiment, the first double strand break is positioned upstream of the the erythroid enhancer within intron 2 (e.g., between TSS+0.75kb to

TSS+52.0kb), and the second double strand break is positioned downstream of the the erythroid enhancer within intron 2 (e.g., between TSS+64.4kb to TSS+84.7kb) (see Fig. 10). In an embodiment, the two double strand breaks are positioned to remove a portion of the erythroid enhancer resulting in disruption of one or more DHSs. In an embodiment, the breaks (i.e., the two double strand breaks) are positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat, or the endogenous splice sites.

The first double strand break may be positioned as follows:

(1) upstream of the 5' end of the erythroid enhancer in intron 2 (e.g., between

TSS+0.75kb to TSS+52.0kb), or

(2) within the erythroid enhancer provided that a portion of the erythroid enhancer is removed resulting in disruption of one or more DHSs (e.g., between TSS+52.0kb to TSS+64.4kb),

and the second double strand break to be paired with the first double strand break may be positioned as follows:

(1) downstream the 3' end of the erythroid enhancer in intron 2 (e.g., between TSS+64.4kb to TSS+84.7kb), or

(2) within the erythroid enhancer provided that a portion of the erythroid

enhancer is removed resulting in disruption of one or more DHSs (e.g., between TSS+52.0kb to TSS+64.4kb).

For example, the first double strand break may be positioned in the BCL11A gene:

(1) between TSS+0.75kb to TSS+lOkb,

(2) between TSS+lOkb to TSS+20kb,

(3) between TSS+20kb to TSS+30kb,

(4) between TSS+30kb to TSS+40kb,

(5) between TSS+40kb to TSS+45kb,

(6) between TSS+45kb to TSS+47.5kb,

(7) between TSS+47.5kb to TSS+50kb,

(8) between TSS+50kb to TSS+5 lkb,

(9) between TSS+5 lkb to TSS+51. lkb,

(10) between TSS+51. lkb to TSS+51.2kb,

(11) between TSS+51.2kb to TSS+51.3kb,

(12) between TSS+51.3kb to TSS+51.4kb,

(13) between TSS+51.4kb to TSS+51.5kb,

(14) between TSS+51.5kb to TSS+51.6kb, (15) between TSS+51.6kb to TSS+51.7kb,

(16) between TSS+51.7kb to TSS+51.8kb,

(17) between TSS+51.8kb to TSS+51.9kb,

(18) between TSS+51.9kb to TSS+52kb,

(19) between TSS+52kb to TSS+53kb,

(20) between TSS+53kb to TSS+54kb,

(21) between TSS+54kb to TSS+55kb,

(22) between TSS+55kb to TSS+56kb,

(23) between TSS+56kb to TSS+57kb,

(24) between TSS+57kb to TSS+58kb,

(25) between TSS+58kb to TSS+59kb,

(26) between TSS+59kb to TSS+60kb,

(27) between TSS+60kb to TSS+61kb,

(28) between TSS+61kb to TSS+62kb,

(29) between TSS+62kb to TSS+63kb,

(30) between TSS+63kb to TSS+64kb, or

(31) between TSS+64kb to TSS+64.4kb,

and the second double strand break to be paired with the first double strand break may be positioned in the BCL11A gene:

(1) between TSS+52kb to TSS+53kb,

(2) between TSS+53kb to TSS+54kb,

(3) between TSS+54kb to TSS+55kb,

(4) between TSS+55kb to TSS+56kb,

(5) between TSS+56kb to TSS+57kb,

(6) between TSS+57kb to TSS+58kb,

(7) between TSS+58kb to TSS+59kb,

(8) between TSS+59kb to TSS+60kb,

(9) between TSS+60kb to TSS+61kb,

(10) between TSS+61kb to TSS+62kb,

(11) between TSS+62kb to TSS+63kb,

(12) between TSS+63kb to TSS+64kb, (13) between TSS+64kb to TSS+64.4kb,

(14) between TSS+64.4kb to TSS+65kb,

(15) between TSS+65kb to TSS+65.1kb,

(16) between TSS+65.1kb to TSS+65.2kb,

(17) between TSS+65.2kb to TSS+65.3kb,

(18) between TSS+65.3kb to TSS+65.4kb,

(19) between TSS+65.4kb to TSS+65.5kb,

(20) between TSS+65.5kb to TSS+65.7kb,

(21) between TSS+65.7kb to TSS+65.8kb,

(22) between TSS+65.8kb to TSS+65.9kb,

(23) between TSS+65.9kb to TSS+66kb,

(24) between TSS+66kb to TSS+67kb,

(25) between TSS+67kb to TSS+68kb,

(26) between TSS+68kb to TSS+69kb,

(27) between TSS+69kb to TSS+70kb,

(28) between TSS+70kb to TSS+75kb,

(29) between TSS+75kb to TSS+80kb, or

(30) between TSS+80kb to TSS+84.4kb.

While not wishing to be bound by theory, it is believed that the two double strand breaks allow for NHEJ-mediated deletion of erythroid enhancer in the BCL11A gene.

In an embodiment, the method comprises introducing a NHEJ-mediated deletion of a genomic sequence including the erythroid enhancer. As described herein, in one embodiment, the method comprises the introduction of two sets of breaks (e.g., one double strand break and a pair of single strand breaks)— one 5' and the other 3' to (i.e., flanking) the BT target position (e.g., the erythroid enhancer). Two gRNAs, e.g., unimolecular (or chimeric) or modular gRNA molecules, are configured to position the two sets of breaks (either the double strand break or the pair of single strand breaks) on opposite sides of the BT target knockdown position (e.g., the erythroid enhancer) in the BCL11A gene. In an embodiment, the first set of breaks (either the double strand break or the pair of single strand breaks) is positioned upstream of the the erythroid enhancer within intron 2 (e.g., between TSS+0.75kb to TSS+52.0kb), and the second set of breaks (either the double strand break or the pair of single strand breaks) is positioned downstream of the the erythroid enhancer within intron 2 (e.g., between TSS+64.4kb to

TSS+84.7kb) (see Fig. 10). In an embodiment, the two sets of breaks (either the double strand break or the pair of single strand breaks) are positioned to remove a portion of the erythroid enhancer resulting in disruption of one or more DHSs. In an embodiment, the breaks (i.e., the two sets of breaks (either the double strand break or the pair of single strand breaks)) are positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat, or the endogenous splice sites.

The first set of breaks (either the double strand break or the pair of single strand breaks) may be positioned as follows:

(1) upstream of the 5' end of the erythroid enhancer in intron 2 (e.g., between TSS+0.75kb to TSS+52.0kb), or

(2) within the erythroid enhancer provided that a portion of the erythroid enhancer is removed resulting in disruption of one or more DHSs (e.g., between

TSS+52.0kb to TSS+64.4kb),

and the second set of breaks (either the double strand break or the pair of single strand breaks) to be paired with the first set of breaks (either the double strand break or the pair of single strand breaks) may be positioned as follows:

(2) within the erythroid enhancer provided that a portion of the erythroid

For example, the first set of breaks (either the double strand break or the pair of single strand breaks) may be positioned in the BCL11A gene:

(1) between TSS+0.75kb to TSS+lOkb,

(2) between TSS+lOkb to TSS+20kb,

(3) between TSS+20kb to TSS+30kb,

(4) between TSS+30kb to TSS+40kb,

(5) between TSS+40kb to TSS+45kb,

(6) between TSS+45kb to TSS+47.5kb,

(7) between TSS+47.5kb to TSS+50kb, 8) between TSS+50kb to TSS+51kb,

9) between TSS+51kb to TSS+51.1kb,

(10) between TSS+51.1kb to TSS+51.2kb,

(11) between TSS+51.2kb to TSS+51.3kb,

(12) between TSS+51.3kb to TSS+51.4kb,

(13) between TSS+51.4kb to TSS+51.5kb,

(14) between TSS+51.5kb to TSS+51.6kb,

(15) between TSS+51.6kb to TSS+51.7kb,

(16) between TSS+51.7kb to TSS+51.8kb,

(17) between TSS+51.8kb to TSS+51.9kb,

(18) between TSS+51.9kb to TSS+52kb,

(19) between TSS+52kb to TSS+53kb,

(20) between TSS+53kb to TSS+54kb,

(21) between TSS+54kb to TSS+55kb,

(22) between TSS+55kb to TSS+56kb,

(23) between TSS+56kb to TSS+57kb,

(24) between TSS+57kb to TSS+58kb,

(25) between TSS+58kb to TSS+59kb,

(26) between TSS+59kb to TSS+60kb,

(27) between TSS+60kb to TSS+61kb,

(28) between TSS+61kb to TSS+62kb,

(29) between TSS+62kb to TSS+63kb,

(30) between TSS+63kb to TSS+64kb, or

(31) between TSS+64kb to TSS+64.4kb,

and the second set of breaks (either the double strand break or the pair of single strand breaks) to be paired with the first set of breaks (either the double strand break or the pair of single strand breaks)may be positioned in the BCLllA gene:

(1) between TSS+52kb to TSS+53kb,

(2) between TSS+53kb to TSS+54kb,

(3) between TSS+54kb to TSS+55kb,

(4) between TSS+55kb to TSS+56kb, 5) between TSS+56kb to TSS+57kb,

6) between TSS+57kb to TSS+58kb,

7) between TSS+58kb to TSS+59kb,

8) between TSS+59kb to TSS+60kb,

9) between TSS+60kb to TSS+61kb,

(10) between TSS+61kb to TSS+62kb,

(11) between TSS+62kb to TSS+63kb,

(12) between TSS+63kb to TSS+64kb,

(13) between TSS+64kb to TSS+64.4kb,

(14) between TSS+64.4kb to TSS+65kb,

(15) between TSS+65kb to TSS+65.1kb,

(16) between TSS+65.1kb to TSS+65.2kb,

(17) between TSS+65.2kb to TSS+65.3kb,

(18) between TSS+65.3kb to TSS+65.4kb,

(19) between TSS+65.4kb to TSS+65.5kb,

(20) between TSS+65.5kb to TSS+65.7kb,

(21) between TSS+65.7kb to TSS+65.8kb,

(22) between TSS+65.8kb to TSS+65.9kb,

(23) between TSS+65.9kb to TSS+66kb,

(24) between TSS+66kb to TSS+67kb,

(25) between TSS+67kb to TSS+68kb,

(26) between TSS+68kb to TSS+69kb,

(27) between TSS+69kb to TSS+70kb,

(28) between TSS+70kb to TSS+75kb,

(29) between TSS+75kb to TSS+80kb, or

(30) between TSS+80kb to TSS+84.4kb.

While not wishing to be bound by theory, it is believed that the two sets of breaks (either the double strand break or the pair of single strand breaks) allow for NHEJ-mediated deletion of erythroid enhancer in the BCL11A gene.

In an embodiment, the method comprises introducing a NHEJ-mediated deletion of a genomic sequence including the erythroid enhancer. As described herein, in one embodiment, the method comprises the introduction of two sets of breaks (e.g., two pairs of single strand breaks)— one 5' and the other 3' to (i.e., flanking) the BT target position (e.g., the erythroid enhancer). Two gRNAs, e.g., unimolecular (or chimeric) or modular gRNA molecules, are configured to position the two sets of breaks on opposite sides of the BT target knockdown position (e.g., the erythroid enhancer) in the BCLllA gene. In an embodiment, the first set of breaks (i.e., the first pair of single strand breaks) is positioned upstream of the the erythroid enhancer within intron 2 (e.g., between TSS+0.75kb to TSS+52.0kb), and the second set of breaks (i.e., the second pair of single strand breaks) is positioned downstream of the the erythroid enhancer within intron 2 (e.g., between TSS+64.4kb to TSS+84.7kb) (see Fig. 10). In an embodiment, the two sets of breaks (e.g., two pairs of single strand breaks)) are positioned to remove a portion of the erythroid enhancer resulting in disruption of one or more DHSs. In an embodiment, the breaks (i.e., the two pairs of single strand breaks) are positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat, or the endogenous splice sites.

The first pair of single strand breaks may be positioned as follows:

TSS+52.0kb to TSS+64.4kb),

and the second pair of single strand breaks to be paired with the first pair of single strand breaks may be positioned as follows:

(2) within the erythroid enhancer provided that a portion of the erythroid

For example, the pair of single strand breaks may be positioned in the BCLllA gene: (1) between TSS+0.75kb to TSS+lOkb,

(2) between TSS+lOkb to TSS+20kb,

(3) between TSS+20kb to TSS+30kb, 4) between TSS+30kb to TSS+40kb,

5) between TSS+40kb to TSS+45kb,

6) between TSS+45kb to TSS+47.5kb,

7) between TSS+47.5kb to TSS+50kb,

8) between TSS+50kb to TSS+51kb,

9) between TSS+51kb to TSS+51.1kb,

(10) between TSS+51.1kb to TSS+51.2kb,

(11) between TSS+51.2kb to TSS+51.3kb,

(12) between TSS+51.3kb to TSS+51.4kb,

(13) between TSS+51.4kb to TSS+51.5kb,

(14) between TSS+51.5kb to TSS+51.6kb,

(15) between TSS+51.6kb to TSS+51.7kb,

(16) between TSS+51.7kb to TSS+51.8kb,

(17) between TSS+51.8kb to TSS+51.9kb,

(18) between TSS+51.9kb to TSS+52kb,

(19) between TSS+52kb to TSS+53kb,

(20) between TSS+53kb to TSS+54kb,

(21) between TSS+54kb to TSS+55kb,

(22) between TSS+55kb to TSS+56kb,

(23) between TSS+56kb to TSS+57kb,

(24) between TSS+57kb to TSS+58kb,

(25) between TSS+58kb to TSS+59kb,

(26) between TSS+59kb to TSS+60kb,

(27) between TSS+60kb to TSS+61kb,

(28) between TSS+61kb to TSS+62kb,

(29) between TSS+62kb to TSS+63kb,

(30) between TSS+63kb to TSS+64kb, or

(31) between TSS+64kb to TSS+64.4kb,

and the second pair of single strand breaks to be paired with the first pair of single strand breaks may be positioned in the BCL11A gene:

(1) between TSS+52kb to TSS+53kb, 2) between TSS+53kb to TSS+54kb,

3) between TSS+54kb to TSS+55kb,

4) between TSS+55kb to TSS+56kb,

5) between TSS+56kb to TSS+57kb,

6) between TSS+57kb to TSS+58kb,

7) between TSS+58kb to TSS+59kb,

8) between TSS+59kb to TSS+60kb,

9) between TSS+60kb to TSS+61kb,

(10) between TSS+61kb to TSS+62kb,

(11) between TSS+62kb to TSS+63kb,

( 12) between TSS+63kb to TSS+64kb,

(13) between TSS+64kb to TSS+64.4kb,

(14) between TSS+64.4kb to TSS+65kb,

(15) between TSS+65kb to TSS+65.1kb,

(16) between TSS+65.1kb to TSS+65.2kb,

(17) between TSS+65.2kb to TSS+65.3kb,

(18) between TSS+65.3kb to TSS+65.4kb,

(19) between TSS+65.4kb to TSS+65.5kb,

(20) between TSS+65.5kb to TSS+65.7kb,

(21) between TSS+65.7kb to TSS+65.8kb,

(22) between TSS+65.8kb to TSS+65.9kb,

(23) between TSS+65.9kb to TSS+66kb,

(24) between TSS+66kb to TSS+67kb,

(25) between TSS+67kb to TSS+68kb,

(26) between TSS+68kb to TSS+69kb,

(27) between TSS+69kb to TSS+70kb,

(28) between TSS+70kb to TSS+75kb,

(29) between TSS+75kb to TSS+80kb, or

(30) between TSS+80kb to TSS+84.4kb. While not wishing to be bound by theory, it is believed that the two sets of breaks (e.g., the two pair of single strand breaks) allow for NHEJ-mediated deletion of erythroid enhancer in the BCLllA gene.

Knocking down the BCLllA gene mediated by an enzymatically inactive Cas9 (eiCas9) molecule or an eiCas9-fusion protein by targeting the promoter region of the gene.

A targeted knockdown approach reduces or eliminates expression of functional BCLllA 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 BCLllA gene.

Methods and compositions discussed herein may be used to alter the expression of the BCLllA gene to treat or prevent BT by targeting a promoter region of the BCLllA gene. In an embodiment, the promoter region, e.g., at least 2 kb, at least 1.5 kb, at least 1.0 kb, or at least 0.5 kb upstream or downstream of the TSS is targeted to knockdown expression of the BCLllA gene. In an embodiment, the methods and compositions discussed herein may be used to knock down the BCLllA gene to treat or prevent BT by targeting 0.5 kb upstream or downstream of the TSS. A targeted knockdown approach reduces or eliminates expression of functional BCLllA 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 BCLllA gene.

Methods to Treat or Prevent BT

Disclosed herein are the approaches to treat or prevent BT, including BTM and BT intermedia, using the compositions and methods described herein.

In one approach, the BCLllA gene is targeted as a targeted knockout or knockdown, e.g., to increase expression of fetal hemoglobin.

While not wishing to be bound by theory, it is considered that increasing levels of fetal hemoglobin (HbF) in subjects with BT may ameliorate disease. Fetal hemoglobin can replace beta hemoglobin in the hemoglobin complex, form adequate tetramers with alpha hemoglobin, and effectively carry oxygen to tissues. Subjects with beta-thalassemia who express higher levels of fetal hemoglobin have been found to have a less severe phenotype. Hydroxyurea, often used in the treatment of beta-thalassemia, may exert its mechanism of action via increasing levels of HbF production.

In an embodiment, knockout or knockdown of the BCLllA gene increases fetal hemoglobin levels in beta-thalassemia subjects and improves phenotype and/or reduces or prevents disease progression. BCL11 A is a zinc-finger repressor that is involved in the regulation of fetal hemoglobin and acts to repress the synthesis of fetal hemoglobin. Knockout of the BCLllA gene in erythroid cells induces increased fetal hemoglobin (HbF) synthesis and increased HbF can result in more effective oxygen carrying capacity in subjects with beta- thalassemia (HbF will form tetramers with hemoglobin alpha).

In an embodiment, the BCLllA knockout or knockdown is targeted specifically to cells of the erythroid lineage. BCLllA knockout in erythroid cells has been found in in vitro studies to have no effect on erythroid growth, maturation and function. In an embodiment, erythroid cells are preferentially targeted, e.g., at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% of the targeted cells are erythroid cells. For example, in the case of in vivo delivery, erythroid cells are preferentially targeted, and if cells are treated ex vivo and returned to the subject, erythroid cells are preferentially modified.

In an embodiment, the methods described herein result in increased fetal hemoglobin synthesis in beta thalassemia subjects, thereby improving disease phenotype in subjects with BT. For example, subjects with beta thalassemia major will suffer from less severe anemia and will need fewer blood transfusions. They will therefore have fewer complications arising from transfusions and chelation therapy. In an embodiment, the method described herein increases fetal hemoglobin synthesis and improves the oxygen carrying capacity of erythroid cells. For example, subjects are expected to demonstrate decreased rates of extramedullary erythropoiesis and decreased erythroid hypertrophy within the bone marrow compared to a subject who has not received the therapy. In an embodiment, the method described herein results in reduction of bone fractures, bone abnormalities, splenomegaly, and thrombosis compared to a subject who has not received the therapy.

Knockdown or knockout of one or both BCLllA alleles may be performed prior to disease onset or after disease onset, but preferably early in the disease course. In an embodiment, the method comprises initiating treatment of a subject prior to disease onset.

In an embodiment, the method comprises initiating treatment of a subject after disease onset.

In an embodiment, the method comprises initiating treatment of a subject well after disease onset, e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 36, 48 or more months after onset of BT, e.g., BTM. While not wishing to be bound by theory it is believed that this treatment may be effective if subjects present well into the course of illness.

In an embodiment, the method comprises initiating treatment of a subject in an advanced stage of disease.

Overall, initiation of treatment for subjects at all stages of disease is expected to prevent negative consequences of disease and be of benefit to subjects.

In an embodiment, the method comprises initiating treatment of a subject prior to disease expression. In an embodiment, the method comprises initiating treatment of a subject in an early stage of disease, e.g., when a subject has tested positive for beta-thalassemia mutations but has no signs or symptoms associated with beta-thalassemia major, minor or intermedia.

In an embodiment, the method comprises initiating treatment of a subject at the appearance of microcytic anemia, e.g., in an infant, child, adult or young adult.

In an embodiment, the method comprises initiating treatment of a subject who is transfusion-dependent.

In an embodiment, the method comprises initiating treatment of a subject who has tested positive for a mutation in a beta globin gene.

In an embodiment, the method comprises initiating treatment at the appearance of any one or more of the following findings associated or consistent with beta-thalassemia major or beta-thalassemia minor: anemia, diarrhea, fever, failure to thrive, frontal bossing, broken long bones, hepatomegaly, splenomegaly, thrombosis, pulmonary embolus, stroke, leg ulcer, cardiomyopathy, cardiac arrhythmia, and evidence of extramedullary erythropoiesis.

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

In an embodiment, allogenic or autologous bone marrow or erythroid cells are treated ex vivo. In an embodiment, an ex vivo treated allogenic or autologous bone marrow or erythroid cells are administered to the subject. In an embodiment, an erythroid cell, e.g., an autologous erythroid cell, is treated ex vivo and returned to the subject. In an embodiment, an autologous stem cell, is treated ex vivo and returned to the subject. In an embodiment, the modified HSCs are administered to the patient following no myeloablative pre-conditioning. In an embodiment, the modified HSCs are administered to the patient following mild myeloablative preconditioning such that following engraftment, some of the hematopoietic cells are devied from the modified HSCs. In other aspects, the HSCs are administered after full myeloablation such that following engraftment, 100% of the hematopoietic cells are derived from the modified HSCs.

In an embodiment, the method comprises delivery of a gRNA molecule and Cas9 molecule by intravenous injection, intramuscular injection, subcutaneous injection, or intra-bone marrow (IBM) injection.

In an embodiment, the method comprises delivery of a gRNA molecule and/or a Cas9 molecule by an AAV. In an embodiment, the method comprises delivery of a gRNA molecule and/or a Cas9 molecule by a lentivirus. In an embodiment, the method comprises delivery of a gRNA molecule and/or a Cas9 molecule by a nanoparticle. In an embodiment, the method comprises delivery of a gRNA molecule and/or a Cas9 molecule by a parvovirus, e.g., a modified parvovirus specifically designed to target bone marrow cells and/or CD4 cells. In an embodiment, two or more gRNA molecules (e.g., a second, third or fourth gRNA molecules) are delivered.

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 Fig. 1. 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

BCLllA gene, e.g., a targeting domain from any of Tables 1A-1F, 2A-2C, 3A- 3E, 4A-4E, 5A-5B, 6A-6D, 7A-7D, 8, 9A-9D, 10A-10D, 11, 12A-12D, 13A-13E, 14A-14B, 15A-15C, 16A-16E, 17A-17C, 18A-18E, 19A-19E, 20A-20C, or 31); 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 BCLllA gene, e.g., a targeting domain from Tables 1A-1F, 2A-2C, 3A-3E, 4A-4E, 5A-5B, 6A- 6D, 7A-7D, 8, 9A-9D, 10A-10D, 11, 12A-12D, 13A-13E, 14A-14B, 15A-15C, 16A-16E, 17A- 17C, 18A-18E, 19A-19E, 20A-20C, or 31; 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.

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 4-9, 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% 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

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, 25 or 26 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.

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.

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 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.

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.

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 modification at the 2' position on ribose), 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 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 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,

1, 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+1-2, 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, 11, 12, 13, 14, 15, 16, 17, or 18, nucleotides in length.

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 an embodiment, 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.

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) 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 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 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.

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 modification (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 an embodiment, 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 first and second complementarity domains are:

independently, 6 +1-2, 1+1-2, 8+/-2, 9+/-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.

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 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.

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 an embodiment, 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 an embodiment, 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 an embodiment 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).

In an embodiment 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 an embodiment, 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 NNNNNNNNNNNNNNNNNNNNGUAUUAGAGCUAUGCUGUAUUGGAAACAAU AC AG 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 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 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, S. aureus or 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.

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 another embodiment, 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 and 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 an embodiment 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 an embodiment, 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 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 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 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 another embodiment, 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. 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 an embodiment, 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). 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 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: 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; (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. 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 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 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, 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,

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,

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 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,

(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,

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,

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,

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

The sequences and structures of exemplary chimeric gRNAs are also shown in Figs. 1H-

II.

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

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, 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, 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.

(e.g., 25 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 5 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.

(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,

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,

(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,

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,

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,

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 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 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.

(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,

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,

(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,

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,

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,

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 Bioinformatics 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, software tools can identify all potential off-target sequences (preceding either NAG or NGG PAMs) across the genome that contain up to a 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 can 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 gRNA vector construction, primer design for the on-target

Surveyor assay, and primer design for high-throughput detection and quantification of off -target cleavage via next-generation 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. 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 or 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. Tarteting domains, disclosed herein, may comprise the 17-mer described in Tables 1A-1F, 2A-2C, 3A-3E, 4A-4E, 5A-5B, 6A-6D, 7A- 7D, 8, 9A-9D, 10A-10D, 11, 12A-12D, 13A-13E, 14A-14B, 15A-15C, 16A-16E, 17A-17C, 18A-18E, 19A-19E, 20A-20C, or 31, e.g., the targeting domains of 18 or more nucleotides may comprise the 17-mer gRNAs described in Tables 1A-1F, 2A-2C, 3A-3E, 4A-4E, 5A-5B, 6A- 6D, 7A-7D, 8, 9A-9D, 10A-10D, 11, 12A-12D, 13A-13E, 14A-14B, 15A-15C, 16A-16E, 17A- 17C, 18A-18E, 19A-19E, 20A-20C, or 31. Tarteting domains, disclosed herein, may comprises the 18-mer described in Tables Tables 1A-1F, 2A-2C, 3A-3E, 4A-4E, 5A-5B, 6A-6D, 7A-7D, 8, 9A-9D, 10A-10D, 11, 12A-12D, 13A-13E, 14A-14B, 15A-15C, 16A-16E, 17A-17C, 18A- 18E, 19A-19E, 20A-20C, or 31, e.g., the targeting domains of 19 or more nucleotides may comprise the 18-mer gRNAs described in Tables 1A-1F, 2A-2C, 3A-3E, 4A-4E, 5A-5B, 6A- 6D, 7A-7D, 8, 9A-9D, 10A-10D, 11, 12A-12D, 13A-13E, 14A-14B, 15A-15C, 16A-16E, 17A- 17C, 18A-18E, 19A-19E, 20A-20C, or 31. Tarteting domains, disclosed herein, may comprises the 19-mer described in Tables 1A-1F, 2A-2C, 3A-3E, 4A-4E, 5A-5B, 6A-6D, 7A-7D, 8, 9A- 9D, 10A-10D, 11, 12A-12D, 13A-13E, 14A-14B, 15A-15C, 16A-16E, 17A-17C, 18A-18E, 19A-19E, 20A-20C, or 31, e.g., the targeting domains of 20 or more nucleotides may comprise the 19-mer gRNAs described in Tables 1A-1F, 2A-2C, 3A-3E, 4A-4E, 5A-5B, 6A-6D, 7A-7D, 8, 9A-9D, 10A-10D, 11, 12A-12D, 13A-13E, 14A-14B, 15A-15C, 16A-16E, 17A-17C, 18A- 18E, 19A-19E, 20A-20C, or 31. Tarteting domains, disclosed herein, may comprises the 20-mer gRNAs described in Tables 1A-1F, 2A-2C, 3A-3E, 4A-4E, 5A-5B, 6A-6D, 7A-7D, 8, 9A-9D, 10A-10D, 11, 12A-12D, 13A-13E, 14A-14B, 15A-15C, 16A-16E, 17A-17C, 18A-18E, 19A- 19E, 20A-20C, or 31, e.g., the targeting domains of 21 or more nucleotides may comprise the 20-mer gRNAs described in Tables 1A-1F, 2A-2C, 3A-3E, 4A-4E, 5A-5B, 6A-6D, 7A-7D, 8, 9A-9D, 10A-10D, 11, 12A-12D, 13A-13E, 14A-14B, 15A-15C, 16A-16E, 17A-17C, 18A-18E, 19A-19E, 20A-20C, or 31. Tarteting domains, disclosed herein, may comprises the 21-mer described in Tables 1A-1F, 2A-2C, 3A-3E, 4A-4E, 5A-5B, 6A-6D, 7A-7D, 8, 9A-9D, 10A- 10D, 11, 12A-12D, 13A-13E, 14A-14B, 15A-15C, 16A-16E, 17A-17C, 18A-18E, 19A-19E, 20A-20C, or 31, e.g., the targeting domains of 22 or more nucleotides may comprise the 21-mer gRNAs described in Tables 1A-1F, 2A-2C, 3A-3E, 4A-4E, 5A-5B, 6A-6D, 7A-7D, 8, 9A-9D, 10A-10D, 11, 12A-12D, 13A-13E, 14A-14B, 15A-15C, 16A-16E, 17A-17C, 18A-18E, 19A- 19E, 20A-20C, or 31. Tarteting domains, disclosed herein, may comprises the 22-mer described in Tables 1A-1F, 2A-2C, 3A-3E, 4A-4E, 5A-5B, 6A-6D, 7A-7D, 8, 9A-9D, 10A-10D, 11, 12A- 12D, 13A-13E, 14A-14B, 15A-15C, 16A-16E, 17A-17C, 18A-18E, 19A-19E, 20A-20C, or 31, e.g., the targeting domains of 23 or more nucleotides may comprise the 22-mer gRNAs described in Tables 1A-1F, 2A-2C, 3A-3E, 4A-4E, 5A-5B, 6A-6D, 7A-7D, 8, 9A-9D, 10A-10D, 11, 12A- 12D, 13A-13E, 14A-14B, 15A-15C, 16A-16E, 17A-17C, 18A-18E, 19A-19E, 20A-20C, or 31.

Tarteting domains, disclosed herein, may comprises the 23-mer described in Tables 1A-1F, 2A- 2C, 3A-3E, 4A-4E, 5A-5B, 6A-6D, 7A-7D, 8, 9A-9D, 10A-10D, 11, 12A-12D, 13A-13E, 14A- 14B, 15A-15C, 16A-16E, 17A-17C, 18A-18E, 19A-19E, 20A-20C, or 31, e.g., the targeting domains of 24 or more nucleotides may comprise the 23-mer gRNAs described in Tables 1A- 1F, 2A-2C, 3A-3E, 4A-4E, 5A-5B, 6A-6D, 7A-7D, 8, 9A-9D, 10A-10D, 11, 12A-12D, 13A- 13E, 14A-14B, 15A-15C, 16A-16E, 17A-17C, 18A-18E, 19A-19E, 20A-20C, or 31. Tarteting domains, disclosed herein, may comprises the 24-mer described in Tables 1A-1F, 2A-2C, 3A- 3E, 4A-4E, 5A-5B, 6A-6D, 7A-7D, 8, 9A-9D, 10A-10D, 11, 12A-12D, 13A-13E, 14A-14B,

15A-15C, 16A-16E, 17A-17C, 18A-18E, 19A-19E, 20A-20C, or 31, e.g., the targeting domains of 25 or more nucleotides may comprise the 24-mer gRNAs described in Tables 1A-1F, 2A-2C, 3A-3E, 4A-4E, 5A-5B, 6A-6D, 7A-7D, 8, 9A-9D, 10A-10D, 11, 12A-12D, 13A-13E, 14A-14B, 15A-15C, 16A-16E, 17A-17C, 18A-18E, 19A-19E, 20A-20C, or 31 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.

Strategies to identify gRNAs for S. pyogenes, S. Aureus, and N. meningitidis to knock out the BCL11 A gene

gRNAs were designed for use with S. pyogenes, S. aureus and N. meningitidis Cas9 enzymes to induce an insertion or deletion of one or more nucleotides mediated by NHEJ in close proximity to or within the early coding region. As an example, three strategies were utilized to identify gRNAs for use with S. pyogenes, S. aureus and N. meningitidis Cas9 enzymes.

In onestrategy, the gRNAs were identified and ranked into 4 tires for S. pyogenes (Tables 1A-1D). The targeting domains for tier 1 gRNA molecules for use with the S. pyogenes Cas9 to knockout the BCL11A gene were selected based on (1) a reasonable distance to the target position, and (2) a high level of orthogonality. Tier 2 gRNAs were selected based on (1), a reasonable distance to the target position, and (2) presence of a 5'G. Tier 3 used the same distance restriction, but removed the requirement of good orthogonality and the 5'G. Tier 4 only required the presence in the coding sequence. Note that tiers are non-inclusive (each gRNA is listed only once). gRNAs for use with the S. aureus (Table IE J, and N. meningitidis (Table IF J Cas9s were identified manually by scanning genomic DNA sequence for the presence of PAM sequences. These gRNAs were not separated into tiers, but were listed in a single list. 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 a second strategy, the gRNAs were identified and ranked into 5 tiers for S. pyogenes (Tables 3A-3E), and S. aureus (Tables 4A-4E); and 2 tiers for N. meningitidis (Tables 5A-5B). For S. pyogenes, and S. aureus, the targeting domain for tier 1 gRNA molecules were selected based on (1) distance to a target site (e.g., the start codon), e.g., within 500bp (e.g., downstream) of the target site (e.g., the start codon), (2) a high level of orthogonality and (3) the presence of a 5 ' G. The targeting domain for tier 2 gRNA molecules were selected based on (1) distance to a target site (e.g., the start codon), e.g., within 500bp (e.g., downstream) of the target site (e.g., the 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., the start codon), e.g., within 500bp (e.g., downstream) of the target site (e.g., the start codon) and (2) the presence of a 5 ' G. The targeting domain for tier 4 gRNA molecules were selected based on distance to a target site (e.g., the start codon), e.g., within 500bp (e.g., downstream) of the target site (e.g., the start codon). The targeting domain for tier 5 gRNA molecules were selected based on distance to the target site (e.g., the 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). For N. meningitidis, the targeting domain for tier 1 gRNA molecules were selected based on (1) distance to a target site (e.g., the start codon), e.g., within 500bp (e.g., downstream) of the target site (e.g., the start codon). The targeting domain for tier 2 gRNA molecules were selected based on distance to the target site (e.g., the 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). 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 a third strategy, the gRNAs were identified and ranked into 3 tiers for S. pyogenes (Tables 12A-12D), and N. meningitidis (Tables 14A-14B); and 5 tiers for S. aureus (Tables 13A-13E). The targeting domain to be used with S. pyogenes Cas9 enzymes for tier 1 gRNA molecules were selected based on (1) distance to a target site (e.g., the start codon), e.g., within 500bp (e.g., downstream) of the target site (e.g., the start codon) and (2) a high level of orthogonality. The targeting domain to be used with S. pyogenes Cas9 enzymes for tier 2 gRNA molecules were selected based on (1) distance to the target site (e.g., the start codon), e.g., within 500bp (e.g., downstream) of the target site (e.g., the start codon). The targeting domain to be used with S. pyogenes Cas9 enzymes for tier 3 gRNA molecules were selected based on distance to the target site (e.g., the 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). The gRNAs were identified and ranked into 5 tiers for S. aureus, when the relevant PAM was NNGRRT or NNGRRV. The targeting domain to be used with S. aureus Cas9 enzymes for tier 1 gRNA molecules were selected based on (1) distance to the target site (e.g., the start codon), e.g., within 500bp (e.g., downstream) of the target site (e.g., the start codon), (2) a high level of orthogonality, and (3) PAM is NNGRRT. The targeting domain to be used with S. aureus Cas9 enzymes for tier 2 gRNA molecules were selected based on (1) distance to the target site (e.g., the start codon), e.g., within 500bp (e.g., downstream) of the target site (e.g., the start codon), and (2) PAM is NNGRRT. The targeting domain to be used with S. aureus Cas9 enzymes for tier 3 gRNA molecules were selected based on (1) distance to a the target site (e.g., the start codon) mutation, e.g., within 500bp (e.g., downstream) of the target site (e.g., the start codon), and (2) PAM is NNGRRV. The targeting domain to be used with S. aureus Cas9 enzymes for tier 4 gRNA molecules were selected based on (1) distance to the target site (e.g., the 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 to be used with S. aureus Cas9 enzymes for tier 5 gRNA molecules were selected based on (1) distance to the target site (e.g., the 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. The gRNAs were identified and ranked into 3 tiers for N. meningitidis. The targeting domain to be used with N. meningitidis Cas9 enzymes for tier 1 gRNA molecules were selected based on (1) distance to the target site, e.g., within 500bp (e.g., downstream) of the target site (e.g., the start codon) and (2) a high level of orthogonality. The targeting domain to be used with N. meningitidis Cas9 enzymes for tier 2 gRNA molecules were selected based on (1) distance to the target site (e.g., the start codon), e.g., within 500bp (e.g., downstream) of the target site (e.g., the start codon). The targeting domain to be used with N. meningitidis Cas9 enzymes for tier 3 gRNA molecules were selected based on distance to the target site (e.g., the 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). 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, when a single gRNA molecule is used to target a Cas9 nickase to create a single strand break in close proximity to the BCLl 1A target position, e.g., the gRNA is used to target either upstream of (e.g., within 500 bp, e.g., within 200 bp upstream of the BCLl 1 A target position), or downstream of (e.g., within 500 bp, e.g., within 200 bp downstream of the BCLl 1A target position) in the BCL11A gene.

In an embodiment, when a single gRNA molecule is used to target a Cas9 nuclease to create a double strand break to in closeproximity to the BCLl 1 A target position, e.g., the gRNA is used to target either upstream of (e.g., within 500 bp, e.g., within 200 bp upstream of the BCLl 1 A target position), or downstream of (e.g., within 500 bp, e.g., within 200 bp downstream of the BCLl 1A target position) in the BCL11A gene.

In an embodiment, dual targeting is used to create two double strand breaks to in closeproximity to the mutation, e.g., the gRNA is used to target either upstream of (e.g., within 500 bp, e.g., within 200 bp upstream of the BCLl 1A target position), or downstream of (e.g., within 500 bp, e.g., within 200 bp downstream of the BCLl 1A target position) in the BCL11A gene. In an embodiment, the first and second gRNAs are used to target two Cas9 nucleases to flank, e.g., the first of gRNA is used to target upstream of (e.g., within 500 bp, e.g., within 200 bp upstream of the BCLl 1 A target position), and the second gRNA is used to target downstream of (e.g., within 500 bp, e.g., within 200 bp downstream of the BCLl 1A target position) in the BCLl 1 A gene.

In an embodiment, dual targeting is used to create a double strand break and a pair of single strand breaks to delete a genomic sequence including the BCLl 1 A target position. In an embodiment, the first, second and third gRNAs are used to target one Cas9 nuclease and two Cas9 nickases to flank, e.g., the first gRNA that will be used with the Cas9 nuclease is used to target upstream of (e.g., within 500 bp, e.g., within 200 bp upstream of the BCLl 1A target position) or downstream of (e.g., within 500 bp, e.g., within 200 bp downstream of the BCLl 1A target position), and the second and third gRNAs that will be used with the Cas9 nickase pair are used to target the opposite side of the mutation (e.g., within 200 bp upstream or downstream of the BCLl 1A target position) in the BCL11A gene.

In an embodiment, when four gRNAs (e.g., two pairs) are used to target four Cas9 nickases to create four single strand breaks to delete genomic sequence including the mutation, the first pair and second pair of gRNAs are used to target four Cas9 nickases to flank, e.g., the first pair of gRNAs are used to target upstream of (e.g., within 500 bp, e.g., within 200 bp upstream of the BCLl 1 A target position), and the second pair of gRNAs are used to target downstream of (e.g., within 500 bp, e.g., within 200 bp downstream of the BCLl 1A target position) in the BCLl 1 A gene.

In an embodiment, dual targeting (e.g., dual nicking) is used to create two nicks on opposite DNA strands by using S. pyogenes, S. aureus and 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. Exemplary nickase pairs including selecting a targeting domain from Group A and a second targeting domain from Group B, or including selecting a targeting domain from Group C and a second targeting domain from Group D in Table 12D (for S. pyogenes). It is contemplated herein that in an embodiment a targeting domain of Group A can be combined with any of the targeting domains of Group B; in an embodiment a targeting domain of Group C can be combined with any of the targeting domains of Group D in Table 12D (for S. pyogenes). For example, BCLl 1A-5355 or BCLl 1 A- 5380 can be combined with BCLl 1A-5321 or BCLl 1A-5416; or BCLl 1A-5333, BCLl 1A-5354, or BCLl lA-5329 can be combined with BCLl lA-5367 or BCLl lA-5341.

Strategies to identify gRNAs for S. pyogenes, S. Aureus, and N. meningitidis to knock down the BCLl 1 A gene

gRNAs were designed for use with one or more of S. pyogenes, S. aureus and N.

meningitidis Cas9 molecules, e.g., enzymatically inactive Cas9 (eiCas9) molecules or Cas9 fusion proteins (e.g., an eiCas9 fused to a transcription repressor domain or chromatin modifying protein to alter (e.g., to block, reduce, or decrease) the transcription of the BCLl 1 A gene. As an example, three strategies were utilized to identify gRNAs for use with S. pyogenes, S. aureus and N. meningitidis one or more Cas9 molecules.

In one strategy, the targeting domains for gRNA molecules to knockdown the BCLl 1 A gene were desgined to target the lkb of sequence 3' of the start codon. They were listed in a single list for S. pyogenes (Table 2A), S. aureus (Table 2B) and N. meningitidis (Table 2C).

In a second strategy, the gRNAs were identified and ranked into 4 tiers for S. pyogenes (Tables 9A-9D), and S. aureus (Tables 10A-10D). The gRNAs were identified and listed in a single list for N. meningitidis (Table 11). For S. pyogenes, and S. aureus, the targeting domain for tier 1 gRNA molecules were selected based on (1) distance to a target site (e.g., a

transcription start site), e.g., within 500bp (e.g., upstream or downstream) of the target site (e.g., the transcription start site) , (2) a high level of orthogonality and (3) the presence of a 5'G. The targeting domain for tier 2 gRNA molecules were selected based on (1) distance to a target site (e.g., the transcription start site), e.g., within 500bp (e.g., upstream or downstream) of the target site (e.g., the transcription start site) 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., the transcription start site), e.g., within 500bp (e.g., upstream or downstream) of the target site (e.g., the transcription start site) and (2) the presence of a 5'G. The targeting domain for tier 4 gRNA molecules were selected based on distance to a target site (e.g., the transcription start site), e.g., within 500bp (e.g., upstream or downstream) of the target site (e.g., the transcription start site). In a third strategy, gRNAs were designed for use with S. pyogenes, S. aureus and N. meningitidis Cas9 molecules. The gRNAs were identified and ranked into 3 tiers for S. pyogenes (Tables 15A-15C). The targeting domain to be used with S. pyogenes Cas9 enzymes for tier 1 gRNA molecules were selected based on (1) distance to a target site (e.g., the transcription start site), e.g., within 500bp (e.g., upstream or downstream) of the target site (e.g., the transcription start site) and (2) a high level of orthogonality. The targeting domain to be used with S.

pyogenes Cas9 enzymes for tier 2 gRNA molecules were selected based on (1) distance to the target site (e.g., the transcription start site), e.g., within 500bp (e.g., upstream or downstream) of the target site (e.g., the transcription start site). The targeting domain to be used with S. pyogenes Cas9 enzymes for tier 3 gRNA molecules were selected based on distance to the target site (e.g., the transcription start site), e.g., within the additional 500 bp upstream and downstream of the transcription start site (i.e., extending to 1 kb upstream and downstream of the transcription start site. The gRNAs were identified and ranked into 5 tiers for S. aureus, when the relevant PAM was NNGRRT or NNGRRV (Tables 16A-16E). The targeting domain to be used with S. aureus Cas9 enzymes for tier 1 gRNA molecules were selected based on (1) distance to the target site (e.g., the transcription start site), e.g., within 500bp (e.g., upstream or downstream) of the target site (e.g., the transcription start site), (2) a high level of orthogonality, and (3) PAM is NNGRRT. The targeting domain to be used with S. aureus Cas9 enzymes for tier 2 gRNA molecules were selected based on (1) distance to the target site (e.g., the transcription start site), e.g., within 500bp (e.g., upstream or downstream) of the target site (e.g., the transcription start site), and (2) PAM is NNGRRT. The targeting domain to be used with S. aureus Cas9 enzymes for tier 3 gRNA molecules were selected based on (1) distance to a target site (e.g., the transcription start site), e.g., within 500bp (e.g., upstream or downstream) of the target site (e.g., the transcription start site), and (2) PAM is NNGRRV. The targeting domain to be used with S. aureus Cas9 enzymes for tier 4 gRNA molecules were selected based on (1) distance to the target site (e.g., the transcription start site), e.g., within the additional 500 bp upstream and downstream of the transcription start site (i.e., extending to 1 kb upstream and downstream of the transcription start site, and (2) PAM is NNGRRT. The targeting domain to be used with S. aureus Cas9 enzymes for tier 5 gRNA molecules were selected based on (1) distance to the target site (e.g., the transcription start site), e.g., within the additional 500 bp upstream and downstream of the transcription start site (i.e., extending to 1 kb upstream and downstream of the transcription start site, and (2) PAM is NNGRRV. The gRNAs were identified and ranked into 3 tiers for N.

meningitidis (Tables 17A-17C). The targeting domain to be used with N. meningitidis Cas9 enzymes for tier 1 gRNA molecules were selected based on (1) distance to a target site (e.g., the transcription start site), e.g., within 500bp (e.g., upstream or downstream) of the target site (e.g., the transcription start site) and (2) a high level of orthogonality. The targeting domain to be used with N. meningitidis Cas9 enzymes for tier 2 gRNA molecules were selected based on (1) distance to the target site (e.g., the transcription start site), e.g., within 500bp (e.g., upstream or downstream) of the target site (e.g., the transcription start site). The targeting domain to be used with N. meningitidis Cas9 enzymes for tier 3 gRNA molecules were selected based on distance to the target site (e.g., the transcription start site), e.g., within the additional 500 bp upstream and downstream of the transcription start site (i.e., extending to 1 kb upstream and downstream of the transcription start site. 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 remove (e.g., delete) the enhancer region the BCL11A gene

gRNAs were designed for use with S. pyogenes, S. aureus and N. meningitidis Cas9 enzymes to remove (e.g., delete) the enhancer region in the BCL11A gene. As an example, two strategies were utilized to identify gRNAs for use with one or more of S. pyogenes, S. aureus and N. meningitidis Cas9 molecules.

In a strategy, the gRNAs were identified and ranked into 4 tiers for S. pyogenes (Tables 6A-6D) and for S. aureus (Tables 7A-7D). The gRNAs were identified and listed in a single list for N. meningitidis (Table 8). The targeting domains for tier 1 gRNA molecules for use with the S. pyogenes, S. aureus Cas9 were selected based on (1) a reasonable distance to the target position, e.g., within a region 5' (51.5 to 51.7kb downstream of transcription start site, TSS) or 3' (65.1 to 65.3kb downstream of TSS), (2) a high level of orthogonality and (3) presence of a 5'G. For selection of tier 2 gRNAs, reasonable distance and high orthogonality were required but the presence of a 5'G was not required. Tier 3 uses the same distance restriction and the requirement for a 5'G, but removes the requirement of good orthogonality. Tier 4 uses the same distance restriction but removes the requirement of good orthogonality and the 5'G. 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 a second strategy, gRNAs were designed for use with S. pyogenes, S. aureus and N. meningitidis Cas9 molecules. The gRNAs were identified and ranked into 4 tiers for S. pyogenes (Tables 18A-18E). The targeting domain to be used with S. pyogenes Cas9 enzymes for tier 1 gRNA molecules were selected based on (1) within a region 5' (51.5 to 51.7kb downstream of TSS) or 3' (65.1 to 65.3kb downstream of TSS), (2) a high level of orthogonality and (3) presence of 5'G. The targeting domain to be used with S. pyogenes Cas9 enzymes for tier 2 gRNA molecules were selected based on (1) within a region 5' (51.5 to 51.7kb downstream of TSS) or 3' (65.1 to 65.3kb downstream of TSS) and (2) a high level of orthogonality. The targeting domain to be used with S. pyogenes Cas9 enzymes for tier 3 gRNA molecules were selected based on (1) within a region 5' (51.5 to 51.7kb downstream of TSS) or 3' (65.1 to 65.3kb downstream of TSS) and (2) presence of 5'G. The targeting domain to be used with S. pyogenes Cas9 enzymes for tier 4 gRNA molecules were selected based on within a region 5' (51.5 to 51.7kb downstream of TSS) or 3' (65.1 to 65.3kb downstream of TSS). The gRNAs were identified and ranked into 5 tiers for S. aureus, when the relevant PAM was NNGRRT or NNGRRV (Tables 19A-19E). The targeting domain to be used with S. aureus Cas9 enzymes for tier 1 gRNA molecules were selected based on (1) within a region 5' (51.5 to 51.7kb downstream of TSS) or 3' (65.1 to 65.3kb downstream of TSS), (2) a high level of orthogonality, (3) ) presence of 5'G and (4) PAM is NNGRRT. The targeting domain to be used with S. aureus Cas9 enzymes for tier 2 gRNA molecules were selected based on (1) within a region 5' (51.5 to 51.7kb downstream of TSS) or 3' (65.1 to 65.3kb downstream of TSS), (2) a high level of orthogonality, and (3) PAM is NNGRRT. The targeting domain to be used with S. aureus Cas9 enzymes for tier 3 gRNA molecules were selected based on (1) within a region 5' (51.5 to 51.7kb downstream of TSS) or 3' (65.1 to 65.3kb downstream of TSS), (2) presence of 5'G and (3) PAM is NNGRRT. The targeting domain to be used with S. aureus Cas9 enzymes for tier 4 gRNA molecules were selected based on (1) within a region 5' (51.5 to 51.7kb downstream of TSS) or 3' (65.1 to 65.3kb downstream of TSS), and (2) PAM is NNGRRT. The targeting domain to be used with S. aureus Cas9 enzymes for tier 5 gRNA molecules were selected based on (1) within a region 5' (51.5 to 51.7kb downstream of TSS) or 3' (65.1 to 65.3kb downstream of TSS), and (2) PAM is NNGRRV. The gRNAs were identified and ranked into 3 tiers for N. meningitidis (Tables 20A-20C). The targeting domain to be used with N. meningitidis Cas9 enzymes for tier 1 gRNA molecules were selected based on (1) within a region 5' (51.5 to 51.7kb downstream of TSS) or 3' (65.1 to 65.3kb downstream of TSS), (2) a high level of orthogonality and (3) presence of 5'G. The targeting domain to be used with N. meningitidis Cas9 enzymes for tier 2 gRNA molecules were selected based on (1) within a region 5' (51.5 to 51.7kb downstream of TSS) or 3' (65.1 to 65.3kb downstream of TSS) and (2) a high level of orthogonality. The targeting domain to be used with N. meningitidis Cas9 enzymes for tier 3 gRNA molecules were selected based on (1) within a region 5' (51.5 to 51.7kb downstream of TSS) or 3' (65.1 to 65.3kb downstream of TSS) and (2) presence of 5'G. The targeting domain to be used with N. meningitidis Cas9 enzymes for tier 4 gRNA molecules were selected based on within a region 5' (51.5 to 51.7kb downstream of TSS) or 3' (65.1 to 65.3kb downstream of TSS). 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, dual targeting (e.g., dual nicking) is used to create two nicks on opposite DNA strands by using S. pyogenes, S. aureus and 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. Exemplary nickase pairs including selecting a targeting domain from Group A and a second targeting domain from Group B, or including selecting a targeting domain from Group C and a second targeting domain from Group D in Table 18E (for S. pyogenes). It is contemplated herein that in an embodiment a targeting domain of Group A can be combined with any of the targeting domains of Group B; in an embodiment a targeting domain of Group C can be combined with any of the targeting domains of Group D in Table 18E (for S. pyogenes). For example, BCL11A-13271 or

BCLl lA-13264 can be combined with BCLl lA-13276; or BCLl lA-13262 or BCLl lA-13282 can be combined with BCLl lA-13290 or BCLl lA-13280.

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 knocking out the BCL11A gene selected according to first tier parameters. The targeting domains are selected based on close proximity to start of the coding sequence 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 Cas9 molecule (e.g., a S. pyogenes Cas9 molecule) that generates a double strand break (Cas9 nuclease) or a single-strand break (Cas9 nickase).

Any of the targeting domains in the table can be used with a Cas9 (e.g., a S. pyogenes Cas9 nickase) molecule to generate a single strand break. In an embodiment, dual targeting is used to create two nicks on opposite DNA strands by using Cas9 nickases (e.g., a S. pyogenes Cas9 nickase) 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 guide RNAs are used to target two Cas9 nucleases (e.g., two S. pyogenes Cas9 nucleases) or two Cas9 nickases (e.g., two S. pyogenes Cas9 nickases), e.g., BCLl lA-31 and BCLl lA-40, BCLl lA-30 and BCLl 1A-42, or BCLl lA-24 and BCL11A- 53 are used. In an embodiment, two 17-mer RNAs are used to target two Cas9 nucleases or two Cas9 nickases, e.g., BCLl 1A-79 and BCLl 1A-90, BCLl 1A-77 and BCLl 1A-92, or BCLl 1 A- 71 and BCLl 1 A- 103 are used.

Table 1A

Table IB provides exemplary targeting domains for knocking out the BCLl 1 A gene selected according to second tier parameters. The targeting domains are selected based on close proximity to start of the coding sequence and presence of a 5' G. 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 generates a double strand break (Cas9 nuclease) or a single- strand break (Cas9 nickase).

Any of the targeting domains in the table can be used with a S. pyogenes Cas9 (nickase) molecule to generate a single strand break. 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

Table 1C provides exemplary targeting domains for knocking out the BCL11A gene selected according to third tier parameters. The targeting domains are selected based on close proximity to start of the coding sequence. 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 generates a double strand break (Cas9 nuclease) or a single-strand break (Cas9 nickase).

Table 1C

BCLllA-20 - AUCAUGACCUCCUCACCUGU 20 451

BCLllA-44 + AUCUCGAUUGGUGAAGGGGA 20 452

BCLllA-67 - AUGACCUCCUCACCUGU 17 453

BCLllA-138 + AUGUGCAGAACGAGGGG 17 454

BCLllA-3 + AUUCCCGU UUGCUUAAGUGC 20 455

BCLllA-95 + AUUGGUGAAGGGGAAGG 17 456

BCLllA-26 - CACAAACGGAAACAAUGCAA 20 457

BCLllA-134 + CACUCAUCCCAGGCGUG 17 458

BCLllA-139 + CAGAACGAGGGGAGGAG 17 459

BCLllA-69 - CAGAUGAACUUCCCAUU 17 460

BCLllA-96 + CAGCUUUUUCUAAGCAG 17 461

BCLllA-86 + CAUCCUCUGGCGUGACC 17 462

BCLllA-93 + CAUCUCGAUUGGUGAAG 17 463

BCLllA-100 + CAUCUGGCACUGCCCAC 17 464

BCLllA-66 - CAUGACCUCCUCACCUG 17 465

BCLllA-99 + CCAAUGGGAAGUUCAUC 17 466

BCLllA-46 + CCACAGCUU UUUCUAAGCAG 20 467

BCLllA-62 - CCAGACCACGGCCCGUU 17 468

BCLllA-68 - CCAGAUGAACUUCCCAU 17 469

BCLllA-8 - CCAGCACUUAAGCAAAC 17 470

BCLllA-107 + CCCAACGGGCCGUGGUC 17 471

BCLllA-7 - CCCAGCACUUAAGCAAA 17 472

BCLllA-49 + CCCCCAAUGGGAAGUUCAUC 20 473

BCLllA-55 + CCCCUUCUGGAGCUCCCAAC 20 474

BCLllA-18 - CCCGUUGGGAGCUCCAGAAG 20 475

BCLllA-9 + CCCGUU UGCUUAAGUGC 17 476

BCLllA-63 - CCGUUGGGAGCUCCAGA 17 477

BCLllA-10 + CCGUUUGCUUAAGUGCU 17 478

BCLllA-27 - CCUCUGCUUAGAAAAAGCUG 20 479

BCLllA-104 + CCUUCUGGAGCUCCCAA 17 480

BCLllA-36 + CGUCAUCCUCUGGCGUGACC 20 481

BCLllA-78 - CGUGGAGGUUGGCAUCC 17 482

BCLllA-64 - CGUUGGGAGCUCCAGAA 17 483

BCLllA-11 + CGUU UGCUUAAGUGCUG 17 484

BCLllA-84 + CUAUGUGUUCCUGUU UG 17 485

BCLllA-136 + CUCCAUGUGCAGAACGA 17 486

BCLllA-128 - CUCUAAUCCCCACGCCU 17 487

BCLllA-118 + CUGCACUCAUCCCAGGCGUG 20 488

BCLllA-74 - CUGCUUAGAAAAAGCUG 17 489

BCLllA-56 + CUGGAGCUCCCAACGGGCCG 20 490

BCLllA-87 + CUGGAUGCCAACCUCCA 17 491

BCLllA-105 + CUUCUGGAGCUCCCAAC 17 492 BCLllA-124 - UAAACUUCUGCACUGGA 17 493

BCLllA-98 + UAAGAAUGUCCCCCAAU 17 494

BCLllA-34 - UAGAGGAAUUUGCCCCAAAC 20 495

BCLllA-131 + UAUUCUGCACUCAUCCC 17 496

BCLllA-137 + U CCAU G U G C AG AACG AG 17 497

BCLllA-122 + UCCAUGUGCAGAACGAGGGG 20 498

BCLllA-126 - UCCCCUCGUUCUGCACA 17 499

BCLllA-54 + UCCCCUUCUGGAGCUCCCAA 20 500

BCLllA-31 - UCCCGUGGAGGUUGGCAUCC 20 501

BCLllA-5 + UCCCGU UUGCUUAAGUGCUG 20 502

BCLllA-110 - UCCUCCCCUCGUUCUGCACA 20 503

BCLllA-94 + UCGAUUGGUGAAGGGGA 17 504

BCLllA-45 + UCGAUUGGUGAAGGGGAAGG 20 505

BCLllA-117 + UCUGCACUCAUCCCAGGCGU 20 506

BCLllA-51 + UCUGGCACUGCCCACAGGUG 20 507

BCLllA-59 + UCUGUAAGAAUGGCUUCAAG 20 508

BCLllA-14 - UGAACCAGACCACGGCCCGU 20 509

BCLllA-132 + UGCACUCAUCCCAGGCG 17 510

BCLllA-129 - UGCAGAAUAUGCCCCGC 17 511

BCLllA-22 - UGCCAGAUGAACUUCCCAUU 20 512

BCLllA-82 + UGCUAUGUGUUCCUGU U 17 513

BCLllA-88 + UGGAUGCCAACCUCCAC 17 514

BCLllA-58 + UGGUUCAUCAUCUGUAAGAA 20 515

BCLllA-33 - UGU UUAUCAACGUCAUCUAG 20 516

BCLllA-80 - UUAUCAACGUCAUCUAG 17 517

BCLllA-25 - UUAUUUUUAUCGAGCACAAA 20 518

BCLllA-108 + UUCAUCAUCUGUAAGAA 17 519

BCLllA-91 + UUCAUCUCGAUUGGUGA 17 520

BCLllA-4 + UUCCCGUUUGCU UAAGUGCU 20 521

BCLllA-116 + UUCUGCACUCAUCCCAGGCG 20 522

BCLllA-43 + UU UCAUCUCGAUUGGUGAAG 20 523

BCLllA-72 - UUUUUAUCGAGCACAAA 17 524

BCLllA-41 + UU UUUCAUCUCGAUUGGUGA 20 525

Table ID provides exemplary targeting domains for knocking out the BCL11A gene selected according to fourth tier parameters. The targeting domains are selected based on presence in the coding sequence. 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 generates a double strand break (Cas9 nuclease) or a single-strand break (Cas9 nickase). Any of the targeting domains in the table can be used with a S. pyogenes Cas9 (nickase) molecule to generate a single strand break. 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 ID

BCLllA-168 - GCGGUUGAAUCCAAUGGCUA 20 554

BCLllA-169 - GGCUAUGGAGCCUCCCGCCA 20 555

BCLllA-170 - CUCCCGCCAUGGAUUUCUCU 20 556

BCLllA-171 - CUCUAGGAGACUUAGAGAGC 20 557

BCLllA-172 - AGGAGACUUAGAGAGCUGGC 20 558

BCLllA-173 - GGAGACUUAGAGAGCUGGCA 20 559

BCLllA-174 - UCUAGCCCACCGCUGUCCCC 20 560

BCLllA-175 - GCCCACCGCUGUCCCCAGGC 20 561

BCLllA-176 - GCCGGCCCAGCCCUAUGCAA 20 562

BCLllA-177 - UUACUGCAACCAUUCCAGCC 20 563

BCLllA-178 - AGGUAGCAAGCCGCCCUUCC 20 564

BCLllA-179 - CCCUCCUCCCUCCCAGCCCC 20 565

BCLllA-180 - UCCAAGUCAUGCGAGUUCUG 20 566

BCLllA-181 - G U U CAAAU U U CAG AG CAACC 20 567

BCLllA-182 - CAAAUUUCAGAGCAACCUGG 20 568

BCLllA-183 - AGAGCAACCUGGUGGUGCAC 20 569

BCLllA-184 - GGUGCACCGGCGCAGCCACA 20 570

BCLllA-185 - GUGCACCGGCGCAGCCACAC 20 571

BCLllA-186 - GUGCGACCACGCGUGCACCC 20 572

BCLllA-187 - GCACAAAUCGUCCCCCAUGA 20 573

BCLllA-188 - AUGACGGUCAAGUCCGACGA 20 574

BCLllA-189 - UCUCUCCACCGCCAGCUCCC 20 575

BCLllA-190 - ACCGCCAGCUCCCCGGAACC 20 576

BCLllA-191 - GGAACCCGGCACCAGCGACU 20 577

BCLllA-192 - ACCCGGCACCAGCGACUUGG 20 578

BCLllA-193 - CCCGGCACCAGCGACUUGGU 20 579

BCLllA-194 - CAG CAG CG CG C U CAAG U CCG 20 580

BCLllA-195 - CAGCGCGCUCAAGUCCGUGG 20 581

BCLllA-196 - GAACGACCCCAACCUGAUCC 20 582

BCLllA-197 - CCCAACCUGAUCCCGGAGAA 20 583

BCLllA-198 - CCAACCUGAUCCCGGAGAAC 20 584

BCLllA-199 - CAACCUGAUCCCGGAGAACG 20 585

BCLllA-200 - GAUCCCGGAGAACGGGGACG 20 586

BCLllA-201 - CCCGGAGAACGGGGACGAGG 20 587

BCLllA-202 - GAACGGGGACGAGGAGGAAG 20 588

BCLllA-203 - CGGGGACGAGGAGGAAGAGG 20 589

BCLllA-204 - GGAGGAAGAGGAGGACGACG 20 590

BCLllA-205 - AGAGGAGGACGACGAGGAAG 20 591

BCLllA-206 - CGACGAGGAAGAGGAAGAAG 20 592

BCLllA-207 - CGAGGAAGAGGAAGAAGAGG 20 593

BCLllA-208 - AGAGGAAGAAGAGGAGGAAG 20 594

BCLllA-209 - GGAAGAAGAGGAGGAAGAGG 20 595 BCLllA-210 - AGAAGAGGAGGAAGAGGAGG 20 596

BCLllA-211 - AGAGGAGGAAGAGGAGGAGG 20 597

BCLllA-212 + UCCUCCUCGUCCCCGUUCUC 20 598

BCLllA-213 + CCUCCUCGUCCCCGUUCUCC 20 599

BCLllA-214 + CGUCCCCGUUCUCCGGGAUC 20 600

BCLllA-215 + CCCGUUCUCCGGGAUCAGGU 20 601

BCLllA-216 + CCGUUCUCCGGGAUCAGGUU 20 602

BCLllA-217 + CGUUCUCCGGGAUCAGGUUG 20 603

BCLllA-218 + GUCGU UCUCGCUCUUGAACU 20 604

BCLllA-219 + GCUCU UGAACUUGGCCACCA 20 605

BCLllA-220 + CACGGACU UGAGCGCGCUGC 20 606

BCLllA-221 + GGCGCUGCCCACCAAGUCGC 20 607

BCLllA-222 + GCCCACCAAGUCGCUGGUGC 20 608

BCLllA-223 + CCCACCAAGUCGCUGGUGCC 20 609

BCLllA-224 + AAGUCGCUGGUGCCGGGUUC 20 610

BCLllA-225 + AGUCGCUGGUGCCGGGUUCC 20 611

BCLllA-226 + GUCGCUGGUGCCGGGU UCCG 20 612

BCLllA-227 + GGUGCCGGGUUCCGGGGAGC 20 613

BCLllA-228 + GCCGGGUUCCGGGGAGCUGG 20 614

BCLllA-229 + GGGU UCCGGGGAGCUGGCGG 20 615

BCLllA-230 + GGCGGUGGAGAGACCGUCGU 20 616

BCLllA-231 + GUCGUCGGACUUGACCGUCA 20 617

BCLllA-232 + UCGUCGGACUUGACCGUCAU 20 618

BCLllA-233 + CGUCGGACU UGACCGUCAUG 20 619

BCLllA-234 + GUCGGACUUGACCGUCAUGG 20 620

BCLllA-235 + UGUGCAUGUGCGUCUUCAUG 20 621

BCLllA-236 + CAUGUGGCGCUUCAGCUUGC 20 622

BCLllA-237 + GGCGCUUCAGCUUGCUGGCC 20 623

BCLllA-238 + GCGCUUCAGCUUGCUGGCCU 20 624

BCLllA-239 + UGCUGGCCUGGGUGCACGCG 20 625

BCLllA-240 + GGGUGCACGCGUGGUCGCAC 20 626

BCLllA-241 + GUCGCACAGGU UGCACU UGU 20 627

BCLllA-242 + UCGCACAGGUUGCACUUGUA 20 628

BCLllA-243 + UGUAGGGCUUCUCGCCCGUG 20 629

BCLllA-244 + UCUCGCCCGUGUGGCUGCGC 20 630

BCLllA-245 + GGCUGCGCCGGUGCACCACC 20 631

BCLllA-246 + GCCGCAGAACUCGCAUGACU 20 632

BCLllA-247 + UCGCAUGACUUGGACUUGAC 20 633

BCLllA-248 + CGCAUGACUUGGACUUGACC 20 634

BCLllA-249 + GCAUGACUUGGACUUGACCG 20 635

BCLllA-250 + CAUGACUUGGACUUGACCGG 20 636

BCLllA-251 + ACU UGGACUUGACCGGGGGC 20 637 BCLllA-252 + CUUGGACUUGACCGGGGGCU 20 638

BCLllA-253 + GGACUUGACCGGGGGCUGGG 20 639

BCLllA-254 + GACUUGACCGGGGGCUGGGA 20 640

BCLllA-255 + UUGACCGGGGGCUGGGAGGG 20 641

BCLllA-256 + ACCGGGGGCUGGGAGGGAGG 20 642

BCLllA-257 + CCGGGGGCUGGGAGGGAGGA 20 643

BCLllA-258 + CGGGGGCUGGGAGGGAGGAG 20 644

BCLllA-259 + GGGCUGGGAGGGAGGAGGGG 20 645

BCLllA-260 + GGAGGAGGGGCGGAUUGCAG 20 646

BCLllA-261 + GGAGGGGCGGAUUGCAGAGG 20 647

BCLllA-262 + GAGGGGCGGAUUGCAGAGGA 20 648

BCLllA-263 + GGGCGGAUUGCAGAGGAGGG 20 649

BCLllA-264 + GGCGGAUUGCAGAGGAGGGA 20 650

BCLllA-265 + GCGGAUUGCAGAGGAGGGAG 20 651

BCLllA-266 + CGGAU UGCAGAGGAGGGAGG 20 652

BCLllA-267 + GGAUUGCAGAGGAGGGAGGG 20 653

BCLllA-268 + GAUUGCAGAGGAGGGAGGGG 20 654

BCLllA-269 + GAGGGAGGGGGGGCGUCGCC 20 655

BCLllA-270 + GAGGGGGGGCGUCGCCAGGA 20 656

BCLllA-271 + AGGGGGGGCGUCGCCAGGAA 20 657

BCLllA-272 + GGGGGCGUCGCCAGGAAGGG 20 658

BCLllA-273 + AGGAAGGGCGGCUUGCUACC 20 659

BCLllA-274 + AGGGCGGCU UGCUACCUGGC 20 660

BCLllA-275 + GGCUUGCUACCUGGCUGGAA 20 661

BCLllA-276 + GGUUGCAGUAACCUUUGCAU 20 662

BCLllA-277 + GUUGCAGUAACCUUUGCAUA 20 663

BCLllA-278 + CAGUAACCUUUGCAUAGGGC 20 664

BCLllA-279 + AGUAACCUUUGCAUAGGGCU 20 665

BCLllA-280 + ACCUU UGCAUAGGGCUGGGC 20 666

BCLllA-281 + UGCAUAGGGCUGGGCCGGCC 20 667

BCLllA-282 + GCAUAGGGCUGGGCCGGCCU 20 668

BCLllA-283 + CAUAGGGCUGGGCCGGCCUG 20 669

BCLllA-284 + CUGGGCCGGCCUGGGGACAG 20 670

BCLllA-285 + GGCCGGCCUGGGGACAGCGG 20 671

BCLllA-286 + GCCGGCCUGGGGACAGCGGU 20 672

BCLllA-287 + AAGUCUCCUAGAGAAAUCCA 20 673

BCLllA-288 + UCUCCUAGAGAAAUCCAUGG 20 674

BCLllA-289 + CUCCUAGAGAAAUCCAUGGC 20 675

BCLllA-290 + CUAGAGAAAUCCAUGGCGGG 20 676

BCLllA-291 + GCGGGAGGCUCCAUAGCCAU 20 677

BCLllA-292 + CAACCGCAGCACCCUGUCAA 20 678

BCLllA-293 + AGCACCCUG UCAAAGGCACU 20 679 BCLllA-294 + GCACCCUGUCAAAGGCACUC 20 680

BCLllA-295 + UGUCAAAGGCACUCGGGUGA 20 681

BCLllA-296 + GUCAAAGGCACUCGGGUGAU 20 682

BCLllA-297 + AAAGGCACUCGGGUGAUGGG 20 683

BCLllA-298 + CACUCGGGUGAUGGGUGGCC 20 684

BCLllA-299 + ACUCGGGUGAUGGGUGGCCA 20 685

BCLllA-300 + GGGCCAUCUCUUCCGCCCCC 20 686

BCLllA-301 + CCGCCCCCAGGCGCUCUAUG 20 687

BCLllA-302 + CCCCCAGGCGCUCUAUGCGG 20 688

BCLllA-303 + CCCCAGGCGCUCUAUGCGGU 20 689

BCLllA-304 + CCCAGGCGCUCUAUGCGGUG 20 690

BCLllA-305 + CCAGGCGCUCUAUGCGGUGG 20 691

BCLllA-306 + UGGGGGUCCAAGUGAUGUCU 20 692

BCLllA-307 + GGGUCCAAGUGAUGUCUCGG 20 693

BCLllA-308 + UCCAAGUGAUGUCUCGGUGG 20 694

BCLllA-309 + GUCUCGGUGGUGGACUAAAC 20 695

BCLllA-310 + UCUCGGUGGUGGACUAAACA 20 696

BCLllA-311 + CUCGGUGGUGGACUAAACAG 20 697

BCLllA-312 + UCGGUGGUGGACUAAACAGG 20 698

BCLllA-313 + CGGUGGUGGACUAAACAGGG 20 699

BCLllA-314 + GGUGGUGGACUAAACAGGGG 20 700

BCLllA-315 + UGGACUAAACAGGGGGGGAG 20 701

BCLllA-316 + GGACUAAACAGGGGGGGAGU 20 702

BCLllA-317 + CUAAACAGGGGGGGAGUGGG 20 703

BCLllA-318 + GUGGAAAGCGCCCUUCUGCC 20 704

BCLllA-319 + AAAGCGCCCUUCUGCCAGGC 20 705

BCLllA-320 + GCCUCUCUCGAUACUGAUCC 20 706

BCLllA-321 + CUGAUCCUGGUAUUCU UAGC 20 707

BCLllA-322 + UGGUAUUCUUAGCAGGUUAA 20 708

BCLllA-323 + GGUAUUCUUAGCAGGUUAAA 20 709

BCLllA-324 + GUAUUCUUAGCAGGUUAAAG 20 710

BCLllA-325 + UGUCUGCAAUAUGAAUCCCA 20 711

BCLllA-326 + GCAAUAUGAAUCCCAUGGAG 20 712

BCLllA-327 + AUAUGAAUCCCAUGGAGAGG 20 713

BCLllA-328 + GAAUCCCAUGGAGAGGUGGC 20 714

BCLllA-329 + AAUCCCAUGGAGAGGUGGCU 20 715

BCLllA-330 + CCAUGGAGAGGUGGCUGGGA 20 716

BCLllA-331 + CAUUCUGCACCUAGUCCUGA 20 717

BCLllA-332 + AUUCUGCACCUAGUCCUGAA 20 718

BCLllA-333 + CCUGAAGGGAUACCAACCCG 20 719

BCLllA-334 + CUGAAGGGAUACCAACCCGC 20 720

BCLllA-335 + UGAAGGGAUACCAACCCGCG 20 721 BCLllA-336 + GGAUACCAACCCGCGGGGUC 20 722

BCLllA-337 + GAUACCAACCCGCGGGGUCA 20 723

BCLllA-338 + AUACCAACCCGCGGGGUCAG 20 724

BCLllA-339 + UUGCAAGAGAAACCAUGCAC 20 725

BCLllA-340 + AGAAACCAUGCACUGGUGAA 20 726

BCLllA-341 + AGUUGUACAUGUGUAGCUGC 20 727

BCLllA-342 + GUUGUACAUGUGUAGCUGCU 20 728

BCLllA-343 - AGCCAUUCACCAGUGCA 17 729

BCLllA-344 - CACGCACAGAACACUCA 17 730

BCLllA-345 - UACUUAGAAAGCGAACA 17 731

BCLllA-346 - GAAGUCCCCUGACCCCG 17 732

BCLllA-347 - AAGUCCCCUGACCCCGC 17 733

BCLllA-348 - CCCCUGACCCCGCGGGU 17 734

BCLllA-349 - CGGGUUGGUAUCCCUUC 17 735

BCLllA-350 - GGUAUCCCUUCAGGACU 17 736

BCLllA-351 - UCCCAGCCACCUCUCCA 17 737

BCLllA-352 - CCCAGCCACCUCUCCAU 17 738

BCLllA-353 - AACCUGCUAAGAAUACC 17 739

BCLllA-354 - AGGAUCAGUAUCGAGAG 17 740

BCLllA-355 - GUAUCGAGAGAGGCUUC 17 741

BCLllA-356 - GAGAGAGGCUUCCGGCC 17 742

BCLllA-357 - GCUUCCGGCCUGGCAGA 17 743

BCLllA-358 - CUUCCGGCCUGGCAGAA 17 744

BCLllA-359 - ACCACCGAGACAUCACU 17 745

BCLllA-360 - CCACCGCAUAGAGCGCC 17 746

BCLllA-361 - CACCGCAUAGAGCGCCU 17 747

BCLllA-362 - ACCGCAUAGAGCGCCUG 17 748

BCLllA-363 - CCGCAUAGAGCGCCUGG 17 749

BCLllA-364 - CAUAGAGCGCCUGGGGG 17 750

BCLllA-365 - CCUGGGGGCGGAAGAGA 17 751

BCLllA-366 - GGCGGAAGAGAUGGCCC 17 752

BCLllA-367 - ACCCGAGUGCCUUUGAC 17 753

BCLllA-368 - CCCGAGUGCCUUUGACA 17 754

BCLllA-369 - CCUUUGACAGGGUGCUG 17 755

BCLllA-370 - GCUGCGGUUGAAUCCAA 17 756

BCLllA-371 - GUUGAAUCCAAUGGCUA 17 757

BCLllA-372 - UAUGGAGCCUCCCGCCA 17 758

BCLllA-373 - CCGCCAUGGAUUUCUCU 17 759

BCLllA-374 - UAGGAGACUUAGAGAGC 17 760

BCLllA-375 - AGACUUAGAGAGCUGGC 17 761

BCLllA-376 - GACUUAGAGAGCUGGCA 17 762

BCLllA-377 - AGCCCACCGCUGUCCCC 17 763 BCLllA-378 - CACCGCUGUCCCCAGGC 17 764

BCLllA-379 - GGCCCAGCCCUAUGCAA 17 765

BCLllA-380 - CUGCAACCAUUCCAGCC 17 766

BCLllA-381 - UAGCAAGCCGCCCUUCC 17 767

BCLllA-382 - UCCUCCCUCCCAGCCCC 17 768

BCLllA-383 - AAGUCAUGCGAGUUCUG 17 769

BCLllA-384 - CAAAU U U CAG AGCAACC 17 770

BCLllA-385 - AUUUCAGAGCAACCUGG 17 771

BCLllA-386 - GCAACCUGGUGGUGCAC 17 772

BCLllA-387 - GCACCGGCGCAGCCACA 17 773

BCLllA-388 - CACCGGCGCAGCCACAC 17 774

BCLllA-389 - CGACCACGCGUGCACCC 17 775

BCLllA-390 - CAAAUCGUCCCCCAUGA 17 776

BCLllA-391 - ACGGUCAAGUCCGACGA 17 111

BCLllA-392 - CUCCACCGCCAGCUCCC 17 778

BCLllA-393 - GCCAGCUCCCCGGAACC 17 779

BCLllA-394 - ACCCGGCACCAGCGACU 17 780

BCLllA-395 - CGGCACCAGCGACUUGG 17 781

BCLllA-396 - GGCACCAGCGACUUGGU 17 782

BCLllA-397 - CAGCGCGCUCAAGUCCG 17 783

BCLllA-398 - CGCGCUCAAGUCCGUGG 17 784

BCLllA-399 - CGACCCCAACCUGAUCC 17 785

BCLllA-400 - AACCUGAUCCCGGAGAA 17 786

BCLllA-401 - ACCUGAUCCCGGAGAAC 17 787

BCLllA-402 - CCUGAUCCCGGAGAACG 17 788

BCLllA-403 - CCCGGAGAACGGGGACG 17 789

BCLllA-404 - GGAGAACGGGGACGAGG 17 790

BCLllA-405 - CGGGGACGAGGAGGAAG 17 791

BCLllA-406 - GGACGAGGAGGAAGAGG 17 792

BCLllA-407 - GGAAGAGGAGGACGACG 17 793

BCLllA-408 - GGAGGACGACGAGGAAG 17 794

BCLllA-409 - CGAGGAAGAGGAAGAAG 17 795

BCLllA-410 - GGAAGAGGAAGAAGAGG 17 796

BCLllA-411 - GGAAGAAGAGGAGGAAG 17 797

BCLllA-412 - AGAAGAGGAGGAAGAGG 17 798

BCLllA-413 - AGAGGAGGAAGAGGAGG 17 799

BCLllA-414 - GGAGGAAGAGGAGGAGG 17 800

BCLllA-415 + UCCUCGUCCCCGUUCUC 17 801

BCLllA-416 + CCUCGUCCCCGUUCUCC 17 802

BCLllA-417 + CCCCGUUCUCCGGGAUC 17 803

BCLllA-418 + GUUCUCCGGGAUCAGGU 17 804

BCLllA-419 + UUCUCCGGGAUCAGGUU 17 805 BCLllA-420 + UCUCCGGGAUCAGGUUG 17 806

BCLllA-421 + GU UCUCGCUCUUGAACU 17 807

BCLllA-422 + CUUGAACUUGGCCACCA 17 808

BCLllA-423 + GGACUUGAGCGCGCUGC 17 809

BCLllA-424 + GCUGCCCACCAAGUCGC 17 810

BCLllA-425 + CACCAAGUCGCUGGUGC 17 811

BCLllA-426 + ACCAAGUCGCUGGUGCC 17 812

BCLllA-427 + UCGCUGGUGCCGGGUUC 17 813

BCLllA-428 + CGCUGGUGCCGGGU UCC 17 814

BCLllA-429 + GCUGGUGCCGGGUUCCG 17 815

BCLllA-430 + GCCGGGUUCCGGGGAGC 17 816

BCLllA-431 + GGGU UCCGGGGAGCUGG 17 817

BCLllA-432 + U UCCGGGGAGCUGGCGG 17 818

BCLllA-433 + GGUGGAGAGACCGUCGU 17 819

BCLllA-434 + GUCGGACUUGACCGUCA 17 820

BCLllA-435 + UCGGACUUGACCGUCAU 17 821

BCLllA-436 + CGGACU UGACCGUCAUG 17 822

BCLllA-437 + GGACU UGACCGUCAUGG 17 823

BCLllA-438 + GCAUGUGCGUCUUCAUG 17 824

BCLllA-439 + GUGGCGCU UCAGCUUGC 17 825

BCLllA-440 + GCUUCAGCUUGCUGGCC 17 826

BCLllA-441 + CUUCAGCUUGCUGGCCU 17 827

BCLllA-442 + UGGCCUGGGUGCACGCG 17 828

BCLllA-443 + UGCACGCGUGGUCGCAC 17 829

BCLllA-444 + GCACAGGUUGCACUUGU 17 830

BCLllA-445 + CACAGGUUGCACUUGUA 17 831

BCLllA-446 + AGGGCUUCUCGCCCGUG 17 832

BCLllA-447 + CGCCCGUGUGGCUGCGC 17 833

BCLllA-448 + UGCGCCGGUGCACCACC 17 834

BCLllA-449 + GCAGAACUCGCAUGACU 17 835

BCLllA-450 + CAUGACUUGGACUUGAC 17 836

BCLllA-451 + AUGACUUGGACUUGACC 17 837

BCLllA-452 + UGACUUGGACUUGACCG 17 838

BCLllA-453 + GACUUGGACUUGACCGG 17 839

BCLllA-454 + UGGACUUGACCGGGGGC 17 840

BCLllA-455 + GGACU UGACCGGGGGCU 17 841

BCLllA-456 + CUUGACCGGGGGCUGGG 17 842

BCLllA-457 + U UGACCGGGGGCUGGGA 17 843

BCLllA-458 + ACCGGGGGCUGGGAGGG 17 844

BCLllA-459 + GGGGGCUGGGAGGGAGG 17 845

BCLllA-460 + GGGGCUGGGAGGGAGGA 17 846

BCLllA-461 + GGGCUGGGAGGGAGGAG 17 847 BCLllA-462 + CUGGGAGGGAGGAGGGG 17 848

BCLllA-463 + GGAGGGGCGGAUUGCAG 17 849

BCLllA-464 + GGGGCGGAUUGCAGAGG 17 850

BCLllA-465 + GGGCGGAUUGCAGAGGA 17 851

BCLllA-466 + CGGAU UGCAGAGGAGGG 17 852

BCLllA-467 + GGAUUGCAGAGGAGGGA 17 853

BCLllA-468 + GAUUGCAGAGGAGGGAG 17 854

BCLllA-469 + AUUGCAGAGGAGGGAGG 17 855

BCLllA-470 + U UGCAGAGGAGGGAGGG 17 856

BCLllA-471 + UGCAGAGGAGGGAGGGG 17 857

BCLllA-472 + GGAGGGGGGGCGUCGCC 17 858

BCLllA-473 + GGGGGGCGUCGCCAGGA 17 859

BCLllA-474 + GGGGGCGUCGCCAGGAA 17 860

BCLllA-475 + GGCGUCGCCAGGAAGGG 17 861

BCLllA-476 + AAGGGCGGCUUGCUACC 17 862

BCLllA-477 + GCGGCUUGCUACCUGGC 17 863

BCLllA-478 + U UGCUACCUGGCUGGAA 17 864

BCLllA-479 + UGCAGUAACCUU UGCAU 17 865

BCLllA-480 + GCAGUAACCUUUGCAUA 17 866

BCLllA-481 + UAACCUUUGCAUAGGGC 17 867

BCLllA-482 + AACCUUUGCAUAGGGCU 17 868

BCLllA-483 + UUUGCAUAGGGCUGGGC 17 869

BCLllA-484 + AUAGGGCUGGGCCGGCC 17 870

BCLllA-485 + UAGGGCUGGGCCGGCCU 17 871

BCLllA-486 + AGGGCUGGGCCGGCCUG 17 872

BCLllA-487 + GGCCGGCCUGGGGACAG 17 873

BCLllA-488 + CGGCCUGGGGACAGCGG 17 874

BCLllA-489 + GGCCUGGGGACAGCGGU 17 875

BCLllA-490 + UCUCCUAGAGAAAUCCA 17 876

BCLllA-491 + CCUAGAGAAAUCCAUGG 17 877

BCLllA-492 + CUAGAGAAAUCCAUGGC 17 878

BCLllA-493 + GAGAAAUCCAUGGCGGG 17 879

BCLllA-494 + GGAGGCUCCAUAGCCAU 17 880

BCLllA-495 + CCGCAGCACCCUGUCAA 17 881

BCLllA-496 + ACCCUGUCAAAGGCACU 17 882

BCLllA-497 + CCCUGUCAAAGGCACUC 17 883

BCLllA-498 + CAAAGGCACUCGGGUGA 17 884

BCLllA-499 + AAAGGCACUCGGGUGAU 17 885

BCLllA-500 + GGCACUCGGGUGAUGGG 17 886

BCLllA-501 + UCGGGUGAUGGGUGGCC 17 887

BCLllA-502 + CGGGUGAUGGGUGGCCA 17 888

BCLllA-503 + CCAUCUCUUCCGCCCCC 17 889 BCLllA-504 + CCCCCAGGCGCUCUAUG 17 890

BCLllA-505 + CCAGGCGCUCUAUGCGG 17 891

BCLllA-506 + CAGGCGCUCUAUGCGGU 17 892

BCLllA-507 + AGGCGCUCUAUGCGGUG 17 893

BCLllA-508 + GGCGCUCUAUGCGGUGG 17 894

BCLllA-509 + GGGUCCAAGUGAUGUCU 17 895

BCLllA-510 + UCCAAGUGAUGUCUCGG 17 896

BCLllA-511 + AAGUGAUGUCUCGGUGG 17 897

BCLllA-512 + UCGGUGGUGGACUAAAC 17 898

BCLllA-513 + CGGUGGUGGACUAAACA 17 899

BCLllA-514 + GGUGGUGGACUAAACAG 17 900

BCLllA-515 + GUGGUGGACUAAACAGG 17 901

BCLllA-516 + UGGUGGACUAAACAGGG 17 902

BCLllA-517 + GGUGGACUAAACAGGGG 17 903

BCLllA-518 + ACUAAACAGGGGGGGAG 17 904

BCLllA-519 + CUAAACAGGGGGGGAGU 17 905

BCLllA-520 + AACAGGGGGGGAGUGGG 17 906

BCLllA-521 + GAAAGCGCCCUUCUGCC 17 907

BCLllA-522 + GCGCCCUUCUGCCAGGC 17 908

BCLllA-523 + UCUCUCGAUACUGAUCC 17 909

BCLllA-524 + AUCCUGGUAUUCUUAGC 17 910

BCLllA-525 + UAUUCUUAGCAGGUUAA 17 911

BCLllA-526 + AUUCUUAGCAGGU UAAA 17 912

BCLllA-527 + UUCUUAGCAGGUUAAAG 17 913

BCLllA-528 + CUGCAAUAUGAAUCCCA 17 914

BCLllA-529 + AUAUGAAUCCCAUGGAG 17 915

BCLllA-530 + UGAAUCCCAUGGAGAGG 17 916

BCLllA-531 + UCCCAUGGAGAGGUGGC 17 917

BCLllA-532 + CCCAUGGAGAGGUGGCU 17 918

BCLllA-533 + UGGAGAGGUGGCUGGGA 17 919

BCLllA-534 + UCUGCACCUAGUCCUGA 17 920

BCLllA-535 + CUGCACCUAGUCCUGAA 17 921

BCLllA-536 + GAAGGGAUACCAACCCG 17 922

BCLllA-537 + AAGGGAUACCAACCCGC 17 923

BCLllA-538 + AGGGAUACCAACCCGCG 17 924

BCLllA-539 + UACCAACCCGCGGGGUC 17 925

BCLllA-540 + ACCAACCCGCGGGGUCA 17 926

BCLllA-541 + CCAACCCGCGGGGUCAG 17 927

BCLllA-542 + CAAGAGAAACCAUGCAC 17 928

BCLllA-543 + AACCAUGCACUGGUGAA 17 929

BCLllA-544 + UGUACAUGUGUAGCUGC 17 930

BCLllA-545 + GUACAUGUGUAGCUGCU 17 931 BCLllA-546 - AGAGGAGGAGGAGGAGCUGA 20 932

BCLllA-547 - AGGAGCUGACGGAGAGCGAG 20 933

BCLllA-548 - GGAGCUGACGGAGAGCGAGA 20 934

BCLllA-549 - GCUGACGGAGAGCGAGAGGG 20 935

BCLllA-550 - GAGAGCGAGAGGGUGGACUA 20 936

BCLllA-551 - GAGAGGGUGGACUACGGCUU 20 937

BCLllA-552 - AGAGGGUGGACUACGGCUUC 20 938

BCLllA-553 - CUACGGCUUCGGGCUGAGCC 20 939

BCLllA-554 - CGGCUUCGGGCUGAGCCUGG 20 940

BCLllA-555 - CUUCGGGCUGAGCCUGGAGG 20 941

BCLllA-556 - GCCACCACGAGAACAGCUCG 20 942

BCLllA-557 - CCACCACGAGAACAGCUCGC 20 943

BCLllA-558 - CACCACGAGAACAGCUCGCG 20 944

BCLllA-559 - CGAGAACAGCUCGCGGGGCG 20 945

BCLllA-560 - CAGCUCGCGGGGCGCGGUCG 20 946

BCLllA-561 - AGCUCGCGGGGCGCGGUCGU 20 947

BCLllA-562 - GCGGGGCGCGGUCGUGGGCG 20 948

BCLllA-563 - CGGGGCGCGGUCGUGGGCGU 20 949

BCLllA-564 - CGCCCUGCCCGACGUCAUGC 20 950

BCLllA-565 - GCCCUGCCCGACGUCAUGCA 20 951

BCLllA-566 - GCCCGACGUCAUGCAGGGCA 20 952

BCLllA-567 - CUCCAUGCAGCACUUCAGCG 20 953

BCLllA-568 - CUUCAGCGAGGCCUUCCACC 20 954

BCLllA-569 - CGAGGCCUUCCACCAGGUCC 20 955

BCLllA-570 - GAGGCCUUCCACCAGGUCCU 20 956

BCLllA-571 - CUGGGCGAGAAGCAUAAGCG 20 957

BCLllA-572 - GAAGCAUAAGCGCGGCCACC 20 958

BCLllA-573 - UAAGCGCGGCCACCUGGCCG 20 959

BCLllA-574 - CGGCCACCUGGCCGAGGCCG 20 960

BCLllA-575 - GGCCACCUGGCCGAGGCCGA 20 961

BCLllA-576 - UGGCCGAGGCCGAGGGCCAC 20 962

BCLllA-577 - GGCCGAGGCCGAGGGCCACA 20 963

BCLllA-578 - GGACACUUGCGACGAAGACU 20 964

BCLllA-579 - CACUUGCGACGAAGACUCGG 20 965

BCLllA-580 - UGCGACGAAGACUCGGUGGC 20 966

BCLllA-581 - AGACUCGGUGGCCGGCGAGU 20 967

BCLllA-582 - GAGUCGGACCGCAUAGACGA 20 968

BCLllA-583 - AUAGACGAUGGCACUGUUAA 20 969

BCLllA-584 - GAUGGCACUGUUAAUGGCCG 20 970

BCLllA-585 - UAAUGGCCGCGGCUGCUCCC 20 971

BCLllA-586 - AAUGGCCGCGGCUGCUCCCC 20 972

BCLllA-587 - CGGCUGCUCCCCGGGCGAGU 20 973 BCLllA-588 - CUCCCCGGGCGAGUCGGCCU 20 974

BCLllA-589 - UCCCCGGGCGAGUCGGCCUC 20 975

BCLllA-590 - CCCCGGGCGAGUCGGCCUCG 20 976

BCLllA-591 - CCCGGGCGAGUCGGCCUCGG 20 977

BCLllA-592 - CCGGGCGAGUCGGCCUCGGG 20 978

BCLllA-593 - CCUGUCCAAAAAGCUGCUGC 20 979

BCLllA-594 - CUGUCCAAAAAGCUGCUGCU 20 980

BCLllA-595 - UAAGCGCAUCAAGCUCGAGA 20 981

BCLllA-596 - GAAGGAGUUCGACCUGCCCC 20 982

BCLllA-597 - CCCGGCCGCGAUGCCCAACA 20 983

BCLllA-598 - CGGAGAACGUGUACUCGCAG 20 984

BCLllA-599 - GUGUACUCGCAGUGGCUCGC 20 985

BCLllA-600 - GCAGUGGCUCGCCGGCUACG 20 986

BCLllA-601 - UCGCCGGCUACGCGGCCUCC 20 987

BCLllA-602 - AAAGAUCCCUUCCUUAGCUU 20 988

BCLllA-603 - AUCGCCUUUUGCCUCCUCGU 20 989

BCLllA-604 - CUCCUCGUCGGAGCACUCCU 20 990

BCLllA-605 - UCGGAGCACUCCUCGGAGAA 20 991

BCLllA-606 - CGGAGCACUCCUCGGAGAAC 20 992

BCLllA-607 - UUGCGCUUCUCCACACCGCC 20 993

BCLllA-608 - UGCGCUUCUCCACACCGCCC 20 994

BCLllA-609 - GCGCUUCUCCACACCGCCCG 20 995

BCLllA-610 - CUCCACACCGCCCGGGGAGC 20 996

BCLllA-611 - ACACCGCCCGGGGAGCUGGA 20 997

BCLllA-612 - CCGCCCGGGGAGCUGGACGG 20 998

BCLllA-613 - CGCCCGGGGAGCUGGACGGA 20 999

BCLllA-614 - GGAGCUGGACGGAGGGAUCU 20 1000

BCLllA-615 - GAGCUGGACGGAGGGAUCUC 20 1001

BCLllA-616 - AGCUGGACGGAGGGAUCUCG 20 1002

BCLllA-617 - GGAGGGAUCUCGGGGCGCAG 20 1003

BCLllA-618 - GAUCUCGGGGCGCAGCGGCA 20 1004

BCLllA-619 - AUCUCGGGGCGCAGCGGCAC 20 1005

BCLllA-620 - GGGCGCAGCGGCACGGGAAG 20 1006

BCLllA-621 - CGCAGCGGCACGGGAAGUGG 20 1007

BCLllA-622 - GCAGCGGCACGGGAAGUGGA 20 1008

BCLllA-623 - GGGAGCACGCCCCAUAUUAG 20 1009

BCLllA-624 - CACGCCCCAUAUUAGUGGUC 20 1010

BCLllA-625 - ACGCCCCAUAUUAGUGGUCC 20 1011

BCLllA-626 - CCAUAUUAGUGGUCCGGGCC 20 1012

BCLllA-627 - CAUAUUAGUGGUCCGGGCCC 20 1013

BCLllA-628 - UUAGUGGUCCGGGCCCGGGC 20 1014

BCLllA-629 - GGGCAGGCCCAGCUCAAAAG 20 1015 BCLllA-630 - GGCAGGCCCAGCUCAAAAGA 20 1016

BCLllA-631 + GCGUCUGCCCUCUUUUGAGC 20 1017

BCLllA-632 + CGUCUGCCCUCUUUUGAGCU 20 1018

BCLllA-633 + UCU UUUGAGCUGGGCCUGCC 20 1019

BCLllA-634 + CUUUUGAGCUGGGCCUGCCC 20 1020

BCLllA-635 + GAGCUGGGCCUGCCCGGGCC 20 1021

BCLllA-636 + CCGGGCCCGGACCACUAAUA 20 1022

BCLllA-637 + CGGGCCCGGACCACUAAUAU 20 1023

BCLllA-638 + GGGCCCGGACCACUAAUAUG 20 1024

BCLllA-639 + GAUCCCUCCGUCCAGCUCCC 20 1025

BCLllA-640 + AUCCCUCCGUCCAGCUCCCC 20 1026

BCLllA-641 + CCUCCGUCCAGCUCCCCGGG 20 1027

BCLllA-642 + GUCCAGCUCCCCGGGCGGUG 20 1028

BCLllA-643 + GCGCAAACUCCCGU UCUCCG 20 1029

BCLllA-644 + CUCCGAGGAGUGCUCCGACG 20 1030

BCLllA-645 + CGAGGAGUGCUCCGACGAGG 20 1031

BCLllA-646 + UGCUCCGACGAGGAGGCAAA 20 1032

BCLllA-647 + GGAGGCAAAAGGCGAUUGUC 20 1033

BCLllA-648 + GUCUGGAGUCUCCGAAGCUA 20 1034

BCLllA-649 + GGAGUCUCCGAAGCUAAGGA 20 1035

BCLllA-650 + GAGUCUCCGAAGCUAAGGAA 20 1036

BCLllA-651 + GAAGGGAUCUUUGAGCUGCC 20 1037

BCLllA-652 + GGGAUCUUUGAGCUGCCUGG 20 1038

BCLllA-653 + CUGCCUGGAGGCCGCGUAGC 20 1039

BCLllA-654 + CGAGUACACGUUCUCCGUGU 20 1040

BCLllA-655 + GAGUACACGUUCUCCGUGUU 20 1041

BCLllA-656 + GUUCUCCGUGUUGGGCAUCG 20 1042

BCLllA-657 + UCCGUGUUGGGCAUCGCGGC 20 1043

BCLllA-658 + CCGUGUUGGGCAUCGCGGCC 20 1044

BCLllA-659 + CGUGU UGGGCAUCGCGGCCG 20 1045

BCLllA-660 + GUGUUGGGCAUCGCGGCCGG 20 1046

BCLllA-661 + UGGGCAUCGCGGCCGGGGGC 20 1047

BCLllA-662 + GAGCUUGAUGCGCUUAGAGA 20 1048

BCLllA-663 + AGCU UGAUGCGCUUAGAGAA 20 1049

BCLllA-664 + GCUUGAUGCGCUUAGAGAAG 20 1050

BCLllA-665 + AGAGAAGGGGCUCAGCGAGC 20 1051

BCLllA-666 + GAGAAGGGGCUCAGCGAGCU 20 1052

BCLllA-667 + AGAAGGGGCUCAGCGAGCUG 20 1053

BCLllA-668 + GCUGCCCAGCAGCAGCU UUU 20 1054

BCLllA-669 + CCAGCAGCAGCUUUUUGGAC 20 1055

BCLllA-670 + CUUUUUGGACAGGCCCCCCG 20 1056

BCLllA-671 + CCCCCCGAGGCCGACUCGCC 20 1057 BCLllA-672 + CCCCCGAGGCCGACUCGCCC 20 1058

BCLllA-673 + CCCCGAGGCCGACUCGCCCG 20 1059

BCLllA-674 + ACUCGCCCGGGGAGCAGCCG 20 1060

BCLllA-675 + UAACAGUGCCAUCGUCUAUG 20 1061

BCLllA-676 + GUCUAUGCGGUCCGACUCGC 20 1062

BCLllA-677 + CUUCGUCGCAAGUGUCCCUG 20 1063

BCLllA-678 + GCAAGUGUCCCUGUGGCCCU 20 1064

BCLllA-679 + GUCCCUGUGGCCCUCGGCCU 20 1065

BCLllA-680 + UGUGGCCCUCGGCCUCGGCC 20 1066

BCLllA-681 + GGCCCUCGGCCUCGGCCAGG 20 1067

BCLllA-682 + CGCGCUUAUGCUUCUCGCCC 20 1068

BCLllA-683 + UAUGCUUCUCGCCCAGGACC 20 1069

BCLllA-684 + GCUUCUCGCCCAGGACCUGG 20 1070

BCLllA-685 + CUCGCCCAGGACCUGGUGGA 20 1071

BCLllA-686 + GGCCUCGCUGAAGUGCUGCA 20 1072

BCLllA-687 + CACCAUGCCCUGCAUGACGU 20 1073

BCLllA-688 + ACCAUGCCCUGCAUGACGUC 20 1074

BCLllA-689 + UGCCCUGCAUGACGUCGGGC 20 1075

BCLllA-690 + GCCCUGCAUGACGUCGGGCA 20 1076

BCLllA-691 + GCAUGACGUCGGGCAGGGCG 20 1077

BCLllA-692 + CGCCCCGCGAGCUGUUCUCG 20 1078

BCLllA-693 + CCCGCGAGCUGUUCUCGUGG 20 1079

BCLllA-694 + CGUGGUGGCGCGCCGCCUCC 20 1080

BCLllA-695 - GGAGGAAGAGGAGGAGG 17 1081

BCLllA-696 - GGAGGAGGAGGAGCUGA 17 1082

BCLllA-697 - AGCUGACGGAGAGCGAG 17 1083

BCLllA-698 - GCUGACGGAGAGCGAGA 17 1084

BCLllA-699 - GACGGAGAGCGAGAGGG 17 1085

BCLllA-700 - AGCGAGAGGGUGGACUA 17 1086

BCLllA-701 - AGGGUGGACUACGGCU U 17 1087

BCLllA-702 - GGGUGGACUACGGCUUC 17 1088

BCLllA-703 - CGGCUUCGGGCUGAGCC 17 1089

BCLllA-704 - CUUCGGGCUGAGCCUGG 17 1090

BCLllA-705 - CGGGCUGAGCCUGGAGG 17 1091

BCLllA-706 - ACCACGAGAACAGCUCG 17 1092

BCLllA-707 - CCACGAGAACAGCUCGC 17 1093

BCLllA-708 - CACGAGAACAGCUCGCG 17 1094

BCLllA-709 - GAACAGCUCGCGGGGCG 17 1095

BCLllA-710 - CUCGCGGGGCGCGGUCG 17 1096

BCLllA-711 - UCGCGGGGCGCGGUCGU 17 1097

BCLllA-712 - GGGCGCGGUCGUGGGCG 17 1098

BCLllA-713 - GGCGCGGUCGUGGGCGU 17 1099 BCLllA-714 - CCUGCCCGACGUCAUGC 17 1100

BCLllA-715 - CUGCCCGACGUCAUGCA 17 1101

BCLllA-716 - CGACGUCAUGCAGGGCA 17 1102

BCLllA-717 - C AU G CAG CAC U U C AG CG 17 1103

BCLllA-718 - CAGCGAGGCCUUCCACC 17 1104

BCLllA-719 - GGCCUUCCACCAGGUCC 17 1105

BCLllA-720 - GCCUUCCACCAGGUCCU 17 1106

BCLllA-721 - GGCGAGAAGCAUAAGCG 17 1107

BCLllA-722 - GCAUAAGCGCGGCCACC 17 1108

BCLllA-723 - GCGCGGCCACCUGGCCG 17 1109

BCLllA-724 - CCACCUGGCCGAGGCCG 17 1110

BCLllA-725 - CACCUGGCCGAGGCCGA 17 1111

BCLllA-726 - CCGAGGCCGAGGGCCAC 17 1112

BCLllA-727 - CGAGGCCGAGGGCCACA 17 1113

BCLllA-728 - CACUUGCGACGAAGACU 17 1114

BCLllA-729 - UUGCGACGAAGACUCGG 17 1115

BCLllA-730 - GACGAAGACUCGGUGGC 17 1116

BCLllA-731 - CUCGGUGGCCGGCGAGU 17 1117

BCLllA-732 - UCGGACCGCAUAGACGA 17 1118

BCLllA-733 - GACGAUGGCACUGUUAA 17 1119

BCLllA-734 - GGCACUGUUAAUGGCCG 17 1120

BCLllA-735 - UGGCCGCGGCUGCUCCC 17 1121

BCLllA-736 - GGCCGCGGCUGCUCCCC 17 1122

BCLllA-737 - CUGCUCCCCGGGCGAGU 17 1123

BCLllA-738 - CCCGGGCGAGUCGGCCU 17 1124

BCLllA-739 - CCGGGCGAGUCGGCCUC 17 1125

BCLllA-740 - CGGGCGAGUCGGCCUCG 17 1126

BCLllA-741 - GGGCGAGUCGGCCUCGG 17 1127

BCLllA-742 - GGCGAGUCGGCCUCGGG 17 1128

BCLllA-743 - GUCCAAAAAGCUGCUGC 17 1129

BCLllA-744 - UCCAAAAAGCUGCUGCU 17 1130

BCLllA-745 - GCGCAUCAAGCUCGAGA 17 1131

BCLllA-746 - GGAGUUCGACCUGCCCC 17 1132

BCLllA-747 - GGCCGCGAUGCCCAACA 17 1133

BCLllA-748 - AGAACGUGUACUCGCAG 17 1134

BCLllA-749 - UACUCGCAGUGGCUCGC 17 1135

BCLllA-750 - GUGGCUCGCCGGCUACG 17 1136

BCLllA-751 - CCGGCUACGCGGCCUCC 17 1137

BCLllA-752 - GAUCCCUUCCUUAGCUU 17 1138

BCLllA-753 - GCCUUUUGCCUCCUCGU 17 1139

BCLllA-754 - CUCGUCGGAGCACUCCU 17 1140

BCLllA-755 - GAGCACUCCUCGGAGAA 17 1141 BCLllA-756 - AG CACU CCU CGG AG AAC 17 1142

BCLllA-757 - CGCUUCUCCACACCGCC 17 1143

BCLllA-758 - GCUUCUCCACACCGCCC 17 1144

BCLllA-759 - CUUCUCCACACCGCCCG 17 1145

BCLllA-760 - CACACCGCCCGGGGAGC 17 1146

BCLllA-761 - CCGCCCGGGGAGCUGGA 17 1147

BCLllA-762 - CCCGGGGAGCUGGACGG 17 1148

BCLllA-763 - CCGGGGAGCUGGACGGA 17 1149

BCLllA-764 - GCUGGACGGAGGGAUCU 17 1150

BCLllA-765 - CUGGACGGAGGGAUCUC 17 1151

BCLllA-766 - UGGACGGAGGGAUCUCG 17 1152

BCLllA-767 - GGGAUCUCGGGGCGCAG 17 1153

BCLllA-768 - CUCGGGGCGCAGCGGCA 17 1154

BCLllA-769 - UCGGGGCGCAGCGGCAC 17 1155

BCLllA-770 - CGCAGCGGCACGGGAAG 17 1156

BCLllA-771 - AGCGGCACGGGAAGUGG 17 1157

BCLllA-772 - GCGGCACGGGAAGUGGA 17 1158

BCLllA-773 - AGCACGCCCCAUAUUAG 17 1159

BCLllA-774 - GCCCCAUAU UAGUGGUC 17 1160

BCLllA-775 - CCCCAUAU UAGUGGUCC 17 1161

BCLllA-776 - UAUUAGUGGUCCGGGCC 17 1162

BCLllA-777 - AUUAGUGGUCCGGGCCC 17 1163

BCLllA-778 - GUGGUCCGGGCCCGGGC 17 1164

BCLllA-779 - CAGG CCCAG CU CAAAAG 17 1165

BCLllA-780 - AG G CCCAG C U CAAAAG A 17 1166

BCLllA-781 + UCUGCCCUCU UUUGAGC 17 1167

BCLllA-782 + CUGCCCUCUU UUGAGCU 17 1168

BCLllA-783 + U UUGAGCUGGGCCUGCC 17 1169

BCLllA-784 + UUGAGCUGGGCCUGCCC 17 1170

BCLllA-785 + CUGGGCCUGCCCGGGCC 17 1171

BCLllA-786 + GGCCCGGACCACUAAUA 17 1172

BCLllA-787 + GCCCGGACCACUAAUAU 17 1173

BCLllA-788 + CCCGGACCACUAAUAUG 17 1174

BCLllA-789 + CCCUCCGUCCAGCUCCC 17 1175

BCLllA-790 + CCUCCGUCCAGCUCCCC 17 1176

BCLllA-791 + CCGUCCAGCUCCCCGGG 17 1177

BCLllA-792 + CAGCUCCCCGGGCGGUG 17 1178

BCLllA-793 + CAAACUCCCGUUCUCCG 17 1179

BCLllA-794 + CGAGGAGUGCUCCGACG 17 1180

BCLllA-795 + GGAGUGCUCCGACGAGG 17 1181

BCLllA-796 + UCCGACGAGGAGGCAAA 17 1182

BCLllA-797 + GGCAAAAGGCGAUUGUC 17 1183 BCLllA-798 + UGGAGUCUCCGAAGCUA 17 1184

BCLllA-799 + GUCUCCGAAGCUAAGGA 17 1185

BCLllA-800 + UCUCCGAAGCUAAGGAA 17 1186

BCLllA-801 + GGGAUCUUUGAGCUGCC 17 1187

BCLllA-802 + AUCUUUGAGCUGCCUGG 17 1188

BCLllA-803 + CCUGGAGGCCGCGUAGC 17 1189

BCLllA-804 + GUACACGUUCUCCGUGU 17 1190

BCLllA-805 + UACACGUUCUCCGUGUU 17 1191

BCLllA-806 + CUCCGUGU UGGGCAUCG 17 1192

BCLllA-807 + GUGUUGGGCAUCGCGGC 17 1193

BCLllA-808 + UGUUGGGCAUCGCGGCC 17 1194

BCLllA-809 + GU UGGGCAUCGCGGCCG 17 1195

BCLllA-810 + UUGGGCAUCGCGGCCGG 17 1196

BCLllA-811 + GCAUCGCGGCCGGGGGC 17 1197

BCLllA-812 + CUUGAUGCGCUUAGAGA 17 1198

BCLllA-813 + U UGAUGCGCU UAGAGAA 17 1199

BCLllA-814 + UGAUGCGCUUAGAGAAG 17 1200

BCLllA-815 + GAAGGGGCUCAGCGAGC 17 1201

BCLllA-816 + AAGGGGCUCAGCGAGCU 17 1202

BCLllA-817 + AGGGGCUCAGCGAGCUG 17 1203

BCLllA-818 + GCCCAGCAGCAGCUUU U 17 1204

BCLllA-819 + GCAGCAGCU UUUUGGAC 17 1205

BCLllA-820 + UUUGGACAGGCCCCCCG 17 1206

BCLllA-821 + CCCGAGGCCGACUCGCC 17 1207

BCLllA-822 + CCGAGGCCGACUCGCCC 17 1208

BCLllA-823 + CGAGGCCGACUCGCCCG 17 1209

BCLllA-824 + CGCCCGGGGAGCAGCCG 17 1210

BCLllA-825 + CAGUGCCAUCGUCUAUG 17 1211

BCLllA-826 + UAUGCGGUCCGACUCGC 17 1212

BCLllA-827 + CGUCGCAAGUGUCCCUG 17 1213

BCLllA-828 + AGUGUCCCUGUGGCCCU 17 1214

BCLllA-829 + CCUGUGGCCCUCGGCCU 17 1215

BCLllA-830 + GGCCCUCGGCCUCGGCC 17 1216

BCLllA-831 + CCUCGGCCUCGGCCAGG 17 1217

BCLllA-832 + GCUUAUGCU UCUCGCCC 17 1218

BCLllA-833 + GCUUCUCGCCCAGGACC 17 1219

BCLllA-834 + UCUCGCCCAGGACCUGG 17 1220

BCLllA-835 + GCCCAGGACCUGGUGGA 17 1221

BCLllA-836 + CUCGCUGAAGUGCUGCA 17 1222

BCLllA-837 + CAUGCCCUGCAUGACGU 17 1223

BCLllA-838 + AUGCCCUGCAUGACGUC 17 1224

BCLllA-839 + CCUGCAUGACGUCGGGC 17 1225 BCLllA-840 + CUGCAUGACGUCGGGCA 17 1226

BCLllA-841 + UGACGUCGGGCAGGGCG 17 1227

BCLllA-842 + CCCGCGAGCUGUUCUCG 17 1228

BCLllA-843 + GCGAGCUGUUCUCGUGG 17 1229

BCLllA-844 + GGUGGCGCGCCGCCUCC 17 1230

BCLllA-845 - CCCAGAGAGCUCAAGAUGUG 20 1231

BCLllA-846 - UCAAGAUGUGUGGCAGUUUU 20 1232

BCLllA-847 - GAUGUGUGGCAGUUUUCGGA 20 1233

BCLllA-848 + GCCACACAUCUUGAGCUCUC 20 1234

BCLllA-849 + CCACACAUCUUGAGCUCUCU 20 1235

BCLllA-850 + UCUCUGGGUACUACGCCGAA 20 1236

BCLllA-851 + CUCUGGGUACUACGCCGAAU 20 1237

BCLllA-852 + UCUGGGUACUACGCCGAAUG 20 1238

BCLllA-853 + CUGGGUACUACGCCGAAUGG 20 1239

BCLllA-854 - CUUCACACACCCCCAUU 17 1240

BCLllA-855 - AGAGAGCUCAAGAUGUG 17 1241

BCLllA-856 - AGAUGUGUGGCAGUUUU 17 1242

BCLllA-857 - GUGUGGCAGUUU UCGGA 17 1243

BCLllA-858 + ACACAUCUUGAGCUCUC 17 1244

BCLllA-859 + CACAUCUUGAGCUCUCU 17 1245

BCLllA-860 + CUGGGUACUACGCCGAA 17 1246

BCLllA-861 + UGGGUACUACGCCGAAU 17 1247

BCLllA-862 + GGGUACUACGCCGAAUG 17 1248

BCLllA-863 + GGUACUACGCCGAAUGG 17 1249

Table IE provides exemplary targeting domains for knocking out the BCL11A gene. 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 generates a double strand break (Cas9 nuclease) or a single-strand break (Cas9 nickase).

Any of the targeting domains in the table can be used with a S. aureus Cas9 (nickase) molecule to generate a single strand break. 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 IE

BCLllA-902 - UUGUUUAUCAACGUCAUCUA 20 1288

BCLllA-903 - UGUUUAUCAACGUCAUCUAG 20 1289

BCLllA-904 - CUAGAGGAAUUUGCCCCAAA 20 1290

BCLllA-905 - UAGAGGAAUUUGCCCCAAAC 20 1291

BCLllA-906 - AGCCAUUCUUACAGAUG 17 1292

BCLllA-907 - AACCAGACCACGGCCCG 17 1293

BCLllA-908 - ACCAGACCACGGCCCGU 17 1294

BCLllA-909 - CCAGACCACGGCCCGUU 17 1295

BCLllA-910 - CGGCCCGUUGGGAGCUC 17 1296

BCLllA-911 - CCCGUUGGGAGCUCCAG 17 1297

BCLllA-912 - CCGUUGGGAGCUCCAGA 17 1298

BCLllA-913 - CGUUGGGAGCUCCAGAA 17 1299

BCLllA-914 - UCAUGACCUCCUCACCU 17 1300

BCLllA-915 - CCUGUGGGCAGUGCCAG 17 1301

BCLllA-916 - GCCAGAUGAACUUCCCA 17 1302

BCLllA-917 - CCAGAUGAACUUCCCAU 17 1303

BCLllA-918 - CAGAUGAACUUCCCAUU 17 1304

BCLllA-919 - AGAUGAACUUCCCAUUG 17 1305

BCLllA-920 - GGACAUUCUUAUUUUUA 17 1306

BCLllA-921 - AUUUUUAUCGAGCACAA 17 1307

BCLllA-922 - UUUUUAUCGAGCACAAA 17 1308

BCLllA-923 - CAAUGGCAGCCUCUGCU 17 1309

BCLllA-924 - UCUGCUUAGAAAAAGCU 17 1310

BCLllA-925 - ACCUUCCCCUUCACCAA 17 1311

BCLllA-926 - CCCCUUCACCAAUCGAG 17 1312

BCLllA-927 - AAAAAGCAUCCAAUCCC 17 1313

BCLllA-928 - AAAAGCAUCCAAUCCCG 17 1314

BCLllA-929 - UGGCAUCCAGGUCACGC 17 1315

BCLllA-930 - GCAUCCAGGUCACGCCA 17 1316

BCLllA-931 - UGUUUAUCAACGUCAUC 17 1317

BCLllA-932 - UUUAUCAACGUCAUCUA 17 1318

BCLllA-933 - UUAUCAACGUCAUCUAG 17 1319

BCLllA-934 - GAGGAAUUUGCCCCAAA 17 1320

BCLllA-935 - AGGAAUUUGCCCCAAAC 17 1321

BCLllA-936 + UCAUCUGUAAGAAUGGCUUC 20 1322

BCLllA-937 + UGGUCUGGUUCAUCAUCUGU 20 1323

BCLllA-938 + AUCCCCUUCUGGAGCUCCCA 20 1324

BCLllA-939 + AGGAGGUCAUGAUCCCCUUC 20 1325

BCLllA-940 + GAGGAGGUCAUGAUCCCCUU 20 1326

BCLllA-941 + UCUGGCACUGCCCACAGGUG 20 1327

BCLllA-942 + AUCUGGCACUGCCCACAGGU 20 1328

BCLllA-943 + UCAUCUGGCACUGCCCACAG 20 1329 BCLllA-944 + AAAUAAGAAUGUCCCCCAAU 20 1330

BCLllA-945 + AAAAUAAGAAUGUCCCCCAA 20 1331

BCLllA-946 + AAAAAUAAGAAUGUCCCCCA 20 1332

BCLllA-947 + CGUUUGUGCUCGAUAAAAAU 20 1333

BCLllA-948 + UAUCCACAGCU UUUUCUAAG 20 1334

BCLllA-949 + U UUCAUCUCGAUUGGUGAAG 20 1335

BCLllA-950 + UUUUCAUCUCGAUUGGUGAA 20 1336

BCLllA-951 + U UUUUCAUCUCGAUUGGUGA 20 1337

BCLllA-952 + UUUUUUCAUCUCGAUUGGUG 20 1338

BCLllA-953 + UGCU UUUUUCAUCUCGAUUG 20 1339

BCLllA-954 + GGAUGCCAACCUCCACGGGA 20 1340

BCLllA-955 + GACCUGGAUGCCAACCUCCA 20 1341

BCLllA-956 + UGACCUGGAUGCCAACCUCC 20 1342

BCLllA-957 + UCGUCAUCCUCUGGCGUGAC 20 1343

BCLllA-958 + CUGCUAUGUGUUCCUGUUUG 20 1344

BCLllA-959 + CUGCUAUGUGUUCCUGUUUG 20 1345

BCLllA-960 + UCUGUAAGAAUGGCUUC 17 1346

BCLllA-961 + UCUGGUUCAUCAUCUGU 17 1347

BCLllA-962 + CCCUUCUGGAGCUCCCA 17 1348

BCLllA-963 + AGGUCAUGAUCCCCUUC 17 1349

BCLllA-964 + GAGGUCAUGAUCCCCUU 17 1350

BCLllA-965 + GGCACUGCCCACAGGUG 17 1351

BCLllA-966 + UGGCACUGCCCACAGGU 17 1352

BCLllA-967 + UCUGGCACUGCCCACAG 17 1353

BCLllA-968 + UAAGAAUGUCCCCCAAU 17 1354

BCLllA-969 + AUAAGAAUGUCCCCCAA 17 1355

BCLllA-970 + AAUAAGAAUGUCCCCCA 17 1356

BCLllA-971 + U UGUGCUCGAUAAAAAU 17 1357

BCLllA-972 + CCACAGCUU UUUCUAAG 17 1358

BCLllA-973 + CAUCUCGAUUGGUGAAG 17 1359

BCLllA-974 + UCAUCUCGAU UGGUGAA 17 1360

BCLllA-975 + U UCAUCUCGAUUGGUGA 17 1361

BCLllA-976 + UUUCAUCUCGAUUGGUG 17 1362

BCLllA-977 + U UUUUUCAUCUCGAUUG 17 1363

BCLllA-978 + UGCCAACCUCCACGGGA 17 1364

BCLllA-979 + CUGGAUGCCAACCUCCA 17 1365

BCLllA-980 + CCUGGAUGCCAACCUCC 17 1366

BCLllA-981 + UCAUCCUCUGGCGUGAC 17 1367

BCLllA-982 + UGCUAUGUGUUCCUGU U 17 1368

BCLllA-983 + CUGCUAUGUGUUCCUGU 17 1369

BCLllA-984 - CUCCUCCCCUCGUUCUGCAC 20 1370

BCLllA-985 - UCCUCCCCUCGUUCUGCACA 20 1371 BCLllA-986 - UGGAGCUCUAAUCCCCACGC 20 1372

BCLllA-987 - GGAGCUCUAAUCCCCACGCC 20 1373

BCLllA-988 - CUCUAAUCCCCACGCCUGGG 20 1374

BCLllA-989 - CCCCACGCCUGGGAUGAGUG 20 1375

BCLllA-990 - UGAGUGCAGAAUAUGCCCCG 20 1376

BCLllA-991 - CUCCCCUCGUUCUGCAC 17 1377

BCLllA-992 - UCCCCUCGUUCUGCACA 17 1378

BCLllA-993 - AGCUCUAAUCCCCACGC 17 1379

BCLllA-994 - GCUCUAAUCCCCACGCC 17 1380

BCLllA-995 - UAAUCCCCACGCCUGGG 17 1381

BCLllA-996 - CACGCCUGGGAUGAGUG 17 1382

BCLllA-997 - GUGCAGAAUAUGCCCCG 17 1383

BCLllA-998 + GAGGAGAGGCCCCUCCAGUG 20 1384

BCLllA-999 + CAUGUGCAGAACGAGGGGAG 20 1385

BCLllA-1000 + UCCAUGUGCAGAACGAGGGG 20 1386

BCLllA-1001 + CUCCAUGUGCAGAACGAGGG 20 1387

BCLllA-1002 + AGCUCCAUGUGCAGAACGAG 20 1388

BCLllA-1003 + GAGCUCCAUGUGCAGAACGA 20 1389

BCLllA-1004 + AGAGCUCCAUGUGCAGAACG 20 1390

BCLllA-1005 + UAGAGCUCCAUGUGCAGAAC 20 1391

BCLllA-1006 + AUUAGAGCUCCAUGUGCAGA 20 1392

BCLllA-1007 + GGGGAUUAGAGCUCCAUGUG 20 1393

BCLllA-1008 + CUCAUCCCAGGCGUGGGGAU 20 1394

BCLllA-1009 + UCUGCACUCAUCCCAGGCGU 20 1395

BCLllA-1010 + UUCUGCACUCAUCCCAGGCG 20 1396

BCLllA-1011 + AUUCUGCACUCAUCCCAGGC 20 1397

BCLllA-1012 + GAGAGGCCCCUCCAGUG 17 1398

BCLllA-1013 + GUGCAGAACGAGGGGAG 17 1399

BCLllA-1014 + AUGUGCAGAACGAGGGG 17 1400

BCLllA-1015 + CAUGUGCAGAACGAGGG 17 1401

BCLllA-1016 + UCCAUGUGCAGAACGAG 17 1402

BCLllA-1017 + CUCCAUGUGCAGAACGA 17 1403

BCLllA-1018 + GCUCCAUGUGCAGAACG 17 1404

BCLllA-1019 + AGCUCCAUGUGCAGAAC 17 1405

BCLllA-1020 + AGAGCUCCAUGUGCAGA 17 1406

BCLllA-1021 + GAUUAGAGCUCCAUGUG 17 1407

BCLllA-1022 + AUCCCAGGCGUGGGGAU 17 1408

BCLllA-1023 + GCACUCAUCCCAGGCGU 17 1409

BCLllA-1024 + UGCACUCAUCCCAGGCG 17 1410

BCLllA-1025 + CUGCACUCAUCCCAGGC 17 1411

BCLllA-1026 - GGU UUCUCUUGCAACACGCA 20 1412

BCLllA-1027 - GCAACACGCACAGAACACUC 20 1413 BCLllA-1028 - GCACAGAACACUCAUGGAUU 20 1414

BCLllA-1029 - UCAUGGAUUAAGAAUCUACU 20 1415

BCLllA-1030 - AU U AAG AAU CU ACU U AG AAA 20 1416

BCLllA-1031 - AAUCUACUUAGAAAGCGAAC 20 1417

BCLllA-1032 - AUCUACUUAGAAAGCGAACA 20 1418

BCLllA-1033 - CACGGAAGUCCCCUGACCCC 20 1419

BCLllA-1034 - CCCGCGGGUUGGUAUCCCUU 20 1420

BCLllA-1035 - UAUCCCUUCAGGACUAGGUG 20 1421

BCLllA-1036 - UCCUUCCCAGCCACCUCUCC 20 1422

BCLllA-1037 - CCUUCCCAGCCACCUCUCCA 20 1423

BCLllA-1038 - AAUAACCCCUUUAACCUGCU 20 1424

BCLllA-1039 - CUUUAACCUGCUAAGAAUAC 20 1425

BCLllA-1040 - UAAGAAUACCAGGAUCAGUA 20 1426

BCLllA-1041 - AGAAUACCAGGAUCAGUAUC 20 1427

BCLllA-1042 - AAUACCAGGAUCAGUAUCGA 20 1428

BCLllA-1043 - GAGAGAGGCUUCCGGCCUGG 20 1429

BCLllA-1044 - AGAGGCUUCCGGCCUGGCAG 20 1430

BCLllA-1045 - CCCCCCUGUUUAGUCCACCA 20 1431

BCLllA-1046 - GUCCACCACCGAGACAUCAC 20 1432

BCLllA-1047 - UCACUUGGACCCCCACCGCA 20 1433

BCLllA-1048 - ACCCCCACCGCAUAGAGCGC 20 1434

BCLllA-1049 - CCCCCACCGCAUAGAGCGCC 20 1435

BCLllA-1050 - CCCCACCGCAUAGAGCGCCU 20 1436

BCLllA-1051 - ACCGCAUAGAGCGCCUGGGG 20 1437

BCLllA-1052 - CCGCAUAGAGCGCCUGGGGG 20 1438

BCLllA-1053 - CAUAGAGCGCCUGGGGGCGG 20 1439

BCLllA-1054 - UGGCCCUGGCCACCCAUCAC 20 1440

BCLllA-1055 - CAUCACCCGAGUGCCUUUGA 20 1441

BCLllA-1056 - CCUUUGACAGGGUGCUGCGG 20 1442

BCLllA-1057 - UGCGGUUGAAUCCAAUGGCU 20 1443

BCLllA-1058 - GCGGUUGAAUCCAAUGGCUA 20 1444

BCLllA-1059 - UGGCUAUGGAGCCUCCCGCC 20 1445

BCLllA-1060 - CCUCCCGCCAUGGAUUUCUC 20 1446

BCLllA-1061 - CUCCCGCCAUGGAUUUCUCU 20 1447

BCLllA-1062 - AUGGAUUUCUCUAGGAGACU 20 1448

BCLllA-1063 - GGAUUUCUCUAGGAGACUUA 20 1449

BCLllA-1064 - UAGGAGACUUAGAGAGCUGG 20 1450

BCLllA-1065 - AGGAGACUUAGAGAGCUGGC 20 1451

BCLllA-1066 - GGAGACUUAGAGAGCUGGCA 20 1452

BCLllA-1067 - CCCGGUCAAGUCCAAGUCAU 20 1453

BCLllA-1068 - GCGGCAAGACGUUCAAAUUU 20 1454

BCLllA-1069 - UGGUGCACCGGCGCAGCCAC 20 1455 BCLllA-1070 - GCACCGGCGCAGCCACACGG 20 1456

BCLllA-1071 - ACCGGCGCAGCCACACGGGC 20 1457

BCLllA-1072 - CGUGCACCCAGGCCAGCAAG 20 1458

BCLllA-1073 - CCAGCAAGCUGAAGCGCCAC 20 1459

BCLllA-1074 - GUCUCUCCACCGCCAGCUCC 20 1460

BCLllA-1075 - UCUCUCCACCGCCAGCUCCC 20 1461

BCLllA-1076 - AACCCGGCACCAGCGACUUG 20 1462

BCLllA-1077 - AGUCCGUGGUGGCCAAGUUC 20 1463

BCLllA-1078 - CGUGGUGGCCAAGUUCAAGA 20 1464

BCLllA-1079 - UGGUGGCCAAGUUCAAGAGC 20 1465

BCLllA-1080 - AGAACGACCCCAACCUGAUC 20 1466

BCLllA-1081 - GAACGACCCCAACCUGAUCC 20 1467

BCLllA-1082 - ACGACCCCAACCUGAUCCCG 20 1468

BCLllA-1083 - CCCCAACCUGAUCCCGGAGA 20 1469

BCLllA-1084 - CCCAACCUGAUCCCGGAGAA 20 1470

BCLllA-1085 - CCAACCUGAUCCCGGAGAAC 20 1471

BCLllA-1086 - CCUGAUCCCGGAGAACGGGG 20 1472

BCLllA-1087 - UGAUCCCGGAGAACGGGGAC 20 1473

BCLllA-1088 - GAUCCCGGAGAACGGGGACG 20 1474

BCLllA-1089 - UCCCGGAGAACGGGGACGAG 20 1475

BCLllA-1090 - CCCGGAGAACGGGGACGAGG 20 1476

BCLllA-1091 - GGAGAACGGGGACGAGGAGG 20 1477

BCLllA-1092 - AGAACGGGGACGAGGAGGAA 20 1478

BCLllA-1093 - GAACGGGGACGAGGAGGAAG 20 1479

BCLllA-1094 - ACGGGGACGAGGAGGAAGAG 20 1480

BCLllA-1095 - CGAGGAGGAAGAGGAGGACG 20 1481

BCLllA-1096 - AGGAGGAAGAGGAGGACGAC 20 1482

BCLllA-1097 - GGAGGAAGAGGAGGACGACG 20 1483

BCLllA-1098 - GGAAGAGGAGGACGACGAGG 20 1484

BCLllA-1099 - AAGAGGAGGACGACGAGGAA 20 1485

BCLllA-1100 - AGAGGAGGACGACGAGGAAG 20 1486

BCLllA-1101 - GGAGGACGACGAGGAAGAGG 20 1487

BCLllA-1102 - GGACGACGAGGAAGAGGAAG 20 1488

BCLllA-1103 - ACGACGAGGAAGAGGAAGAA 20 1489

BCLllA-1104 - CGACGAGGAAGAGGAAGAAG 20 1490

BCLllA-1105 - ACGAGGAAGAGGAAGAAGAG 20 1491

BCLllA-1106 - CGAGGAAGAGGAAGAAGAGG 20 1492

BCLllA-1107 - GGAAGAGGAAGAAGAGGAGG 20 1493

BCLllA-1108 - AAGAGGAAGAAGAGGAGGAA 20 1494

BCLllA-1109 - AGAGGAAGAAGAGGAGGAAG 20 1495

BCLllA-1110 - AGGAAGAAGAGGAGGAAGAG 20 1496

BCLllA-1111 - GGAAGAAGAGGAGGAAGAGG 20 1497 BCLllA-1112 - AAGAAGAGGAGGAAGAGGAG 20 1498

BCLllA-1113 - AGAAGAGGAGGAAGAGGAGG 20 1499

BCLllA-1114 - AAGAGGAGGAAGAGGAGGAG 20 1500

BCLllA-1115 - AGAGGAGGAAGAGGAGGAGG 20 1501

BCLllA-1116 - AAGAGGAGGAGGAGGAGCUG 20 1502

BCLllA-1117 - AGAGGAGGAGGAGGAGCUGA 20 1503

BCLllA-1118 - AGGAGGAGGAGGAGCUGACG 20 1504

BCLllA-1119 - GGAGGAGGAGCUGACGGAGA 20 1505

BCLllA-1120 - AGGAGGAGCUGACGGAGAGC 20 1506

BCLllA-1121 - GAGGAGCUGACGGAGAGCGA 20 1507

BCLllA-1122 - AGCUGACGGAGAGCGAGAGG 20 1508

BCLllA-1123 - CGAGAGGGUGGACUACGGCU 20 1509

BCLllA-1124 - GGGUGGACUACGGCUUCGGG 20 1510

BCLllA-1125 - ACUACGGCUUCGGGCUGAGC 20 1511

BCLllA-1126 - CUACGGCUUCGGGCUGAGCC 20 1512

BCLllA-1127 - CCUGGAGGCGGCGCGCCACC 20 1513

BCLllA-1128 - UGGAGGCGGCGCGCCACCAC 20 1514

BCLllA-1129 - CGCCACCACGAGAACAGCUC 20 1515

BCLllA-1130 - GCCACCACGAGAACAGCUCG 20 1516

BCLllA-1131 - ACAGCUCGCGGGGCGCGGUC 20 1517

BCLllA-1132 - CGCGGGGCGCGGUCGUGGGC 20 1518

BCLllA-1133 - CGCGGUCGUGGGCGUGGGCG 20 1519

BCLllA-1134 - CGGUCGUGGGCGUGGGCGAC 20 1520

BCLllA-1135 - GCGCCCUGCCCGACGUCAUG 20 1521

BCLllA-1136 - CAGCUCCAUGCAGCACUUCA 20 1522

BCLllA-1137 - GCGAGGCCUUCCACCAGGUC 20 1523

BCLllA-1138 - GGCCUUCCACCAGGUCCUGG 20 1524

BCLllA-1139 - CCUUCCACCAGGUCCUGGGC 20 1525

BCLllA-1140 - GCAUAAGCGCGGCCACCUGG 20 1526

BCLllA-1141 - GCGCGGCCACCUGGCCGAGG 20 1527

BCLllA-1142 - GCGGCCACCUGGCCGAGGCC 20 1528

BCLllA-1143 - CUGGCCGAGGCCGAGGGCCA 20 1529

BCLllA-1144 - UGGCCGAGGCCGAGGGCCAC 20 1530

BCLllA-1145 - GGGCCACAGGGACACUUGCG 20 1531

BCLllA-1146 - CGACGAAGACUCGGUGGCCG 20 1532

BCLllA-1147 - AAGACUCGGUGGCCGGCGAG 20 1533

BCLllA-1148 - UUAAUGGCCGCGGCUGCUCC 20 1534

BCLllA-1149 - UGGCCGCGGCUGCUCCCCGG 20 1535

BCLllA-1150 - GCUCCCCGGGCGAGUCGGCC 20 1536

BCLllA-1151 - CUCCCCGGGCGAGUCGGCCU 20 1537

BCLllA-1152 - UCCCCGGGCGAGUCGGCCUC 20 1538

BCLllA-1153 - CCCCGGGCGAGUCGGCCUCG 20 1539 BCLllA-1154 - GCCUGUCCAAAAAGCUGCUG 20 1540

BCLllA-1155 - UGCUGGGCAGCCCCAGCUCG 20 1541

BCLllA-1156 - CUUCUCUAAGCGCAUCAAGC 20 1542

BCLllA-1157 - UCUCUAAGCGCAUCAAGCUC 20 1543

BCLllA-1158 - CUAAGCGCAUCAAGCUCGAG 20 1544

BCLllA-1159 - UAAGCGCAUCAAGCUCGAGA 20 1545

BCLllA-1160 - CCCCGGCCGCGAUGCCCAAC 20 1546

BCLllA-1161 - CCCGGCCGCGAUGCCCAACA 20 1547

BCLllA-1162 - CGGCCGCGAUGCCCAACACG 20 1548

BCLllA-1163 - CAAAGAUCCCUUCCUUAGCU 20 1549

BCLllA-1164 - AAAGAUCCCUUCCUUAGCUU 20 1550

BCLllA-1165 - AAUCGCCUUUUGCCUCCUCG 20 1551

BCLllA-1166 - AUCGCCUUUUGCCUCCUCGU 20 1552

BCLllA-1167 - CCUCCUCGUCGGAGCACUCC 20 1553

BCLllA-1168 - CUCCUCGUCGGAGCACUCCU 20 1554

BCLllA-1169 - CCUCGUCGGAGCACUCCUCG 20 1555

BCLllA-1170 - GUCGGAGCACUCCUCGGAGA 20 1556

BCLllA-1171 - UCGGAGCACUCCUCGGAGAA 20 1557

BCLllA-1172 - CGGAGCACUCCUCGGAGAAC 20 1558

BCLllA-1173 - UUUGCGCUUCUCCACACCGC 20 1559

BCLllA-1174 - UUGCGCUUCUCCACACCGCC 20 1560

BCLllA-1175 - UGCGCUUCUCCACACCGCCC 20 1561

BCLllA-1176 - GCGCUUCUCCACACCGCCCG 20 1562

BCLllA-1177 - UCUCCACACCGCCCGGGGAG 20 1563

BCLllA-1178 - CACACCGCCCGGGGAGCUGG 20 1564

BCLllA-1179 - ACACCGCCCGGGGAGCUGGA 20 1565

BCLllA-1180 - ACCGCCCGGGGAGCUGGACG 20 1566

BCLllA-1181 - CCGCCCGGGGAGCUGGACGG 20 1567

BCLllA-1182 - GGGAGCUGGACGGAGGGAUC 20 1568

BCLllA-1183 - GGAGCUGGACGGAGGGAUCU 20 1569

BCLllA-1184 - GGAUCUCGGGGCGCAGCGGC 20 1570

BCLllA-1185 - GAUCUCGGGGCGCAGCGGCA 20 1571

BCLllA-1186 - AUCUCGGGGCGCAGCGGCAC 20 1572

BCLllA-1187 - GGGGCGCAGCGGCACGGGAA 20 1573

BCLllA-1188 - GGGCGCAGCGGCACGGGAAG 20 1574

BCLllA-1189 - GCGCAGCGGCACGGGAAGUG 20 1575

BCLllA-1190 - CGCAGCGGCACGGGAAGUGG 20 1576

BCLllA-1191 - GCAGCGGCACGGGAAGUGGA 20 1577

BCLllA-1192 - GCACGCCCCAUAUUAGUGGU 20 1578

BCLllA-1193 - CCCAUAUUAGUGGUCCGGGC 20 1579

BCLllA-1194 - CCCGGGCAGGCCCAGCUCAA 20 1580

BCLllA-1195 - CGGGCAGGCCCAGCUCAAAA 20 1581 BCLllA-1196 - UUCUCUUGCAACACGCA 17 1582

BCLllA-1197 - ACACGCACAGAACACUC 17 1583

BCLllA-1198 - CAGAACACUCAUGGAUU 17 1584

BCLllA-1199 - UGGAUUAAGAAUCUACU 17 1585

BCLllA-1200 - AAGAAUCUACUUAGAAA 17 1586

BCLllA-1201 - CUACUUAGAAAGCGAAC 17 1587

BCLllA-1202 - UACUUAGAAAGCGAACA 17 1588

BCLllA-1203 - GGAAGUCCCCUGACCCC 17 1589

BCLllA-1204 - GCGGGUUGGUAUCCCUU 17 1590

BCLllA-1205 - CCCUUCAGGACUAGGUG 17 1591

BCLllA-1206 - UUCCCAGCCACCUCUCC 17 1592

BCLllA-1207 - UCCCAGCCACCUCUCCA 17 1593

BCLllA-1208 - AACCCCUUUAACCUGCU 17 1594

BCLllA-1209 - UAACCUGCUAAGAAUAC 17 1595

BCLllA-1210 - GAAUACCAGGAUCAGUA 17 1596

BCLllA-1211 - AUACCAGGAUCAGUAUC 17 1597

BCLllA-1212 - ACCAGGAUCAGUAUCGA 17 1598

BCLllA-1213 - AGAGGCUUCCGGCCUGG 17 1599

BCLllA-1214 - GGCUUCCGGCCUGGCAG 17 1600

BCLllA-1215 - CCCUGUUUAGUCCACCA 17 1601

BCLllA-1216 - CACCACCGAGACAUCAC 17 1602

BCLllA-1217 - CUUGGACCCCCACCGCA 17 1603

BCLllA-1218 - CCCACCGCAUAGAGCGC 17 1604

BCLllA-1219 - CCACCGCAUAGAGCGCC 17 1605

BCLllA-1220 - CACCGCAUAGAGCGCCU 17 1606

BCLllA-1221 - GCAUAGAGCGCCUGGGG 17 1607

BCLllA-1222 - CAUAGAGCGCCUGGGGG 17 1608

BCLllA-1223 - AGAGCGCCUGGGGGCGG 17 1609

BCLllA-1224 - CCCUGGCCACCCAUCAC 17 1610

BCLllA-1225 - CACCCGAGUGCCUUUGA 17 1611

BCLllA-1226 - UUGACAGGGUGCUGCGG 17 1612

BCLllA-1227 - GGUUGAAUCCAAUGGCU 17 1613

BCLllA-1228 - GUUGAAUCCAAUGGCUA 17 1614

BCLllA-1229 - CUAUGGAGCCUCCCGCC 17 1615

BCLllA-1230 - CCCGCCAUGGAUUUCUC 17 1616

BCLllA-1231 - CCGCCAUGGAUUUCUCU 17 1617

BCLllA-1232 - GAUUUCUCUAGGAGACU 17 1618

BCLllA-1233 - UUUCUCUAGGAGACUUA 17 1619

BCLllA-1234 - GAGACUUAGAGAGCUGG 17 1620

BCLllA-1235 - AGACUUAGAGAGCUGGC 17 1621

BCLllA-1236 - GACUUAGAGAGCUGGCA 17 1622

BCLllA-1237 - G G U CAAG U CCAAG U CAU 17 1623 BCLllA-1238 - GCAAGACG U U CAAAU U U 17 1624

BCLllA-1239 - UGCACCGGCGCAGCCAC 17 1625

BCLllA-1240 - CCGGCGCAGCCACACGG 17 1626

BCLllA-1241 - GGCGCAGCCACACGGGC 17 1627

BCLllA-1242 - GCACCCAGGCCAGCAAG 17 1628

BCLllA-1243 - GCAAGCUGAAGCGCCAC 17 1629

BCLllA-1244 - UCUCCACCGCCAGCUCC 17 1630

BCLllA-1245 - CUCCACCGCCAGCUCCC 17 1631

BCLllA-1246 - CCGGCACCAGCGACUUG 17 1632

BCLllA-1247 - CCGUGGUGGCCAAGUUC 17 1633

BCLllA-1248 - GGUGGCCAAGUUCAAGA 17 1634

BCLllA-1249 - UGGCCAAG U U CAAG AG C 17 1635

BCLllA-1250 - ACGACCCCAACCUGAUC 17 1636

BCLllA-1251 - CGACCCCAACCUGAUCC 17 1637

BCLllA-1252 - ACCCCAACCUGAUCCCG 17 1638

BCLllA-1253 - CAACCUGAUCCCGGAGA 17 1639

BCLllA-1254 - AACCUGAUCCCGGAGAA 17 1640

BCLllA-1255 - ACCUGAUCCCGGAGAAC 17 1641

BCLllA-1256 - GAUCCCGGAGAACGGGG 17 1642

BCLllA-1257 - UCCCGGAGAACGGGGAC 17 1643

BCLllA-1258 - CCCGGAGAACGGGGACG 17 1644

BCLllA-1259 - CGGAGAACGGGGACGAG 17 1645

BCLllA-1260 - GGAGAACGGGGACGAGG 17 1646

BCLllA-1261 - GAACGGGGACGAGGAGG 17 1647

BCLllA-1262 - ACGGGGACGAGGAGGAA 17 1648

BCLllA-1263 - CGGGGACGAGGAGGAAG 17 1649

BCLllA-1264 - GGGACGAGGAGGAAGAG 17 1650

BCLllA-1265 - GGAGGAAGAGGAGGACG 17 1651

BCLllA-1266 - AGGAAGAGGAGGACGAC 17 1652

BCLllA-1267 - GGAAGAGGAGGACGACG 17 1653

BCLllA-1268 - AGAGGAGGACGACGAGG 17 1654

BCLllA-1269 - AGGAGGACGACGAGGAA 17 1655

BCLllA-1270 - GGAGGACGACGAGGAAG 17 1656

BCLllA-1271 - GGACGACGAGGAAGAGG 17 1657

BCLllA-1272 - CGACGAGGAAGAGGAAG 17 1658

BCLllA-1273 - ACGAGGAAGAGGAAGAA 17 1659

BCLllA-1274 - CGAGGAAGAGGAAGAAG 17 1660

BCLllA-1275 - AGGAAGAGGAAGAAGAG 17 1661

BCLllA-1276 - GGAAGAGGAAGAAGAGG 17 1662

BCLllA-1277 - AGAGGAAGAAGAGGAGG 17 1663

BCLllA-1278 - AGGAAGAAGAGGAGGAA 17 1664

BCLllA-1279 - GGAAGAAGAGGAGGAAG 17 1665 BCLllA-1280 - AAGAAGAGGAGGAAGAG 17 1666

BCLllA-1281 - AGAAGAGGAGGAAGAGG 17 1667

BCLllA-1282 - AAGAGGAGGAAGAGGAG 17 1668

BCLllA-1283 - AGAGGAGGAAGAGGAGG 17 1669

BCLllA-1284 - AGGAGGAAGAGGAGGAG 17 1670

BCLllA-1285 - GGAGGAAGAGGAGGAGG 17 1671

BCLllA-1286 - AGGAGGAGGAGGAGCUG 17 1672

BCLllA-1287 - GGAGGAGGAGGAGCUGA 17 1673

BCLllA-1288 - AGGAGGAGGAGCUGACG 17 1674

BCLllA-1289 - GGAGGAGCUGACGGAGA 17 1675

BCLllA-1290 - AGGAGCUGACGGAGAGC 17 1676

BCLllA-1291 - GAGCUGACGGAGAGCGA 17 1677

BCLllA-1292 - UGACGGAGAGCGAGAGG 17 1678

BCLllA-1293 - GAGGGUGGACUACGGCU 17 1679

BCLllA-1294 - UGGACUACGGCUUCGGG 17 1680

BCLllA-1295 - ACGGCUUCGGGCUGAGC 17 1681

BCLllA-1296 - CGGCUUCGGGCUGAGCC 17 1682

BCLllA-1297 - GGAGGCGGCGCGCCACC 17 1683

BCLllA-1298 - AGGCGGCGCGCCACCAC 17 1684

BCLllA-1299 - CACCACGAGAACAGCUC 17 1685

BCLllA-1300 - ACCACGAGAACAGCUCG 17 1686

BCLllA-1301 - GCUCGCGGGGCGCGGUC 17 1687

BCLllA-1302 - GGGGCGCGGUCGUGGGC 17 1688

BCLllA-1303 - GGUCGUGGGCGUGGGCG 17 1689

BCLllA-1304 - UCGUGGGCGUGGGCGAC 17 1690

BCLllA-1305 - CCCUGCCCGACGUCAUG 17 1691

BCLllA-1306 - CUCCAUGCAGCACUUCA 17 1692

BCLllA-1307 - AGGCCUUCCACCAGGUC 17 1693

BCLllA-1308 - CUUCCACCAGGUCCUGG 17 1694

BCLllA-1309 - UCCACCAGGUCCUGGGC 17 1695

BCLllA-1310 - UAAGCGCGGCCACCUGG 17 1696

BCLllA-1311 - CGGCCACCUGGCCGAGG 17 1697

BCLllA-1312 - GCCACCUGGCCGAGGCC 17 1698

BCLllA-1313 - GCCGAGGCCGAGGGCCA 17 1699

BCLllA-1314 - CCGAGGCCGAGGGCCAC 17 1700

BCLllA-1315 - CCACAGGGACACUUGCG 17 1701

BCLllA-1316 - CGAAGACUCGGUGGCCG 17 1702

BCLllA-1317 - ACUCGGUGGCCGGCGAG 17 1703

BCLllA-1318 - AUGGCCGCGGCUGCUCC 17 1704

BCLllA-1319 - CCGCGGCUGCUCCCCGG 17 1705

BCLllA-1320 - CCCCGGGCGAGUCGGCC 17 1706

BCLllA-1321 - CCCGGGCGAGUCGGCCU 17 1707 BCLllA-1322 - CCGGGCGAGUCGGCCUC 17 1708

BCLllA-1323 - CGGGCGAGUCGGCCUCG 17 1709

BCLllA-1324 - UGUCCAAAAAGCUGCUG 17 1710

BCLllA-1325 - UGGGCAGCCCCAGCUCG 17 1711

BCLllA-1326 - CUCUAAGCGCAUCAAGC 17 1712

BCLllA-1327 - CUAAGCGCAUCAAGCUC 17 1713

BCLllA-1328 - AGCGCAUCAAGCUCGAG 17 1714

BCLllA-1329 - GCGCAUCAAGCUCGAGA 17 1715

BCLllA-1330 - CGGCCGCGAUGCCCAAC 17 1716

BCLllA-1331 - GGCCGCGAUGCCCAACA 17 1717

BCLllA-1332 - CCGCGAUGCCCAACACG 17 1718

BCLllA-1333 - AGAUCCCUUCCUUAGCU 17 1719

BCLllA-1334 - GAUCCCUUCCUUAGCUU 17 1720

BCLllA-1335 - CGCCUUUUGCCUCCUCG 17 1721

BCLllA-1336 - GCCUUUUGCCUCCUCGU 17 1722

BCLllA-1337 - CCUCGUCGGAGCACUCC 17 1723

BCLllA-1338 - CUCGUCGGAGCACUCCU 17 1724

BCLllA-1339 - CGUCGGAGCACUCCUCG 17 1725

BCLllA-1340 - GGAGCACUCCUCGGAGA 17 1726

BCLllA-1341 - GAGCACUCCUCGGAGAA 17 1727

BCLllA-1342 - AGCACUCCUCGGAGAAC 17 1728

BCLllA-1343 - GCGCUUCUCCACACCGC 17 1729

BCLllA-1344 - CGCUUCUCCACACCGCC 17 1730

BCLllA-1345 - GCUUCUCCACACCGCCC 17 1731

BCLllA-1346 - CUUCUCCACACCGCCCG 17 1732

BCLllA-1347 - CCACACCGCCCGGGGAG 17 1733

BCLllA-1348 - ACCGCCCGGGGAGCUGG 17 1734

BCLllA-1349 - CCGCCCGGGGAGCUGGA 17 1735

BCLllA-1350 - GCCCGGGGAGCUGGACG 17 1736

BCLllA-1351 - CCCGGGGAGCUGGACGG 17 1737

BCLllA-1352 - AGCUGGACGGAGGGAUC 17 1738

BCLllA-1353 - GCUGGACGGAGGGAUCU 17 1739

BCLllA-1354 - UCUCGGGGCGCAGCGGC 17 1740

BCLllA-1355 - CUCGGGGCGCAGCGGCA 17 1741

BCLllA-1356 - UCGGGGCGCAGCGGCAC 17 1742

BCLllA-1357 - GCGCAGCGGCACGGGAA 17 1743

BCLllA-1358 - CGCAGCGGCACGGGAAG 17 1744

BCLllA-1359 - CAGCGGCACGGGAAGUG 17 1745

BCLllA-1360 - AGCGGCACGGGAAGUGG 17 1746

BCLllA-1361 - GCGGCACGGGAAGUGGA 17 1747

BCLllA-1362 - CGCCCCAUAUUAGUGGU 17 1748

BCLllA-1363 - AUAUUAGUGGUCCGGGC 17 1749 BCLllA-1364 - GGGCAGGCCCAGCUCAA 17 1750

BCLllA-1365 - G CAG G CCC AG CU C AAAA 17 1751

BCLllA-1366 + AAGUUGUACAUGUGUAGCUG 20 1752

BCLllA-1367 + GCAAGAGAAACCAUGCACUG 20 1753

BCLllA-1368 + GUGUUCUGUGCGUGU UGCAA 20 1754

BCLllA-1369 + GAGUGUUCUGUGCGUGUUGC 20 1755

BCLllA-1370 + UCUAAGUAGAUUCUUAAUCC 20 1756

BCLllA-1371 + GAUACCAACCCGCGGGGUCA 20 1757

BCLllA-1372 + GGAUACCAACCCGCGGGGUC 20 1758

BCLllA-1373 + GGGAUACCAACCCGCGGGGU 20 1759

BCLllA-1374 + CCUGAAGGGAUACCAACCCG 20 1760

BCLllA-1375 + UCCUGAAGGGAUACCAACCC 20 1761

BCLllA-1376 + CAUUCUGCACCUAGUCCUGA 20 1762

BCLllA-1377 + ACAUUCUGCACCUAGUCCUG 20 1763

BCLllA-1378 + AGGACAUUCUGCACCUAGUC 20 1764

BCLllA-1379 + CCCAUGGAGAGGUGGCUGGG 20 1765

BCLllA-1380 + AAUCCCAUGGAGAGGUGGCU 20 1766

BCLllA-1381 + GAAUCCCAUGGAGAGGUGGC 20 1767

BCLllA-1382 + UGAAUCCCAUGGAGAGGUGG 20 1768

BCLllA-1383 + UCUGCAAUAUGAAUCCCAUG 20 1769

BCLllA-1384 + UGUCUGCAAUAUGAAUCCCA 20 1770

BCLllA-1385 + UUGUCUGCAAUAUGAAUCCC 20 1771

BCLllA-1386 + AAGGGGUUAUUGUCUGCAAU 20 1772

BCLllA-1387 + UGGUAUUCUUAGCAGGUUAA 20 1773

BCLllA-1388 + CUGGUAUUCUUAGCAGGUUA 20 1774

BCLllA-1389 + AAAGCGCCCUUCUGCCAGGC 20 1775

BCLllA-1390 + GAAAGCGCCCUUCUGCCAGG 20 1776

BCLllA-1391 + CUAAACAGGGGGGGAGUGGG 20 1777

BCLllA-1392 + ACUAAACAGGGGGGGAGUGG 20 1778

BCLllA-1393 + GUGGACUAAACAGGGGGGGA 20 1779

BCLllA-1394 + GGUGGUGGACUAAACAGGGG 20 1780

BCLllA-1395 + CGGUGGUGGACUAAACAGGG 20 1781

BCLllA-1396 + UCGGUGGUGGACUAAACAGG 20 1782

BCLllA-1397 + CUCGGUGGUGGACUAAACAG 20 1783

BCLllA-1398 + UCUCGGUGGUGGACUAAACA 20 1784

BCLllA-1399 + GUCUCGGUGGUGGACUAAAC 20 1785

BCLllA-1400 + UGUCUCGGUGGUGGACUAAA 20 1786

BCLllA-1401 + GUCCAAGUGAUGUCUCGGUG 20 1787

BCLllA-1402 + CCCCAGGCGCUCUAUGCGGU 20 1788

BCLllA-1403 + CCCCCAGGCGCUCUAUGCGG 20 1789

BCLllA-1404 + GCCCCCAGGCGCUCUAUGCG 20 1790

BCLllA-1405 + GCACUCGGGUGAUGGGUGGC 20 1791 BCLllA-1406 + CUGUCAAAGGCACUCGGGUG 20 1792

BCLllA-1407 + C AG CACCCUGU CAAAG G CAC 20 1793

BCLllA-1408 + GGCGGGAGGCUCCAUAGCCA 20 1794

BCLllA-1409 + CUCCUAGAGAAAUCCAUGGC 20 1795

BCLllA-1410 + UCUCCUAGAGAAAUCCAUGG 20 1796

BCLllA-1411 + GUCUCCUAGAGAAAUCCAUG 20 1797

BCLllA-1412 + CCAGCUCUCUAAGUCUCCUA 20 1798

BCLllA-1413 + UGCCAGCUCUCUAAGUCUCC 20 1799

BCLllA-1414 + GGGCCGGCCUGGGGACAGCG 20 1800

BCLllA-1415 + GCAUAGGGCUGGGCCGGCCU 20 1801

BCLllA-1416 + UGCAUAGGGCUGGGCCGGCC 20 1802

BCLllA-1417 + U UGCAUAGGGCUGGGCCGGC 20 1803

BCLllA-1418 + GCAGUAACCUUUGCAUAGGG 20 1804

BCLllA-1419 + UGGUUGCAGUAACCUU UGCA 20 1805

BCLllA-1420 + AGGGCGGCUUGCUACCUGGC 20 1806

BCLllA-1421 + AAGGGCGGCUUGCUACCUGG 20 1807

BCLllA-1422 + GGAGGGGGGGCGUCGCCAGG 20 1808

BCLllA-1423 + GAGGGAGGGGGGGCGUCGCC 20 1809

BCLllA-1424 + GGAGGGAGGGGGGGCGUCGC 20 1810

BCLllA-1425 + CGGAUUGCAGAGGAGGGAGG 20 1811

BCLllA-1426 + GCGGAUUGCAGAGGAGGGAG 20 1812

BCLllA-1427 + GGCGGAUUGCAGAGGAGGGA 20 1813

BCLllA-1428 + GGGCGGAUUGCAGAGGAGGG 20 1814

BCLllA-1429 + GGGGCGGAUUGCAGAGGAGG 20 1815

BCLllA-1430 + GAGGGGCGGAUUGCAGAGGA 20 1816

BCLllA-1431 + GGAGGGGCGGAUUGCAGAGG 20 1817

BCLllA-1432 + AGGAGGGGCGGAUUGCAGAG 20 1818

BCLllA-1433 + GGAGGAGGGGCGGAUUGCAG 20 1819

BCLllA-1434 + GGGAGGAGGGGCGGAUUGCA 20 1820

BCLllA-1435 + GAGGGAGGAGGGGCGGAUUG 20 1821

BCLllA-1436 + GGGGCUGGGAGGGAGGAGGG 20 1822

BCLllA-1437 + ACCGGGGGCUGGGAGGGAGG 20 1823

BCLllA-1438 + GACCGGGGGCUGGGAGGGAG 20 1824

BCLllA-1439 + UUGACCGGGGGCUGGGAGGG 20 1825

BCLllA-1440 + CUUGACCGGGGGCUGGGAGG 20 1826

BCLllA-1441 + GACUUGACCGGGGGCUGGGA 20 1827

BCLllA-1442 + GGACUUGACCGGGGGCUGGG 20 1828

BCLllA-1443 + UGGACUUGACCGGGGGCUGG 20 1829

BCLllA-1444 + CUUGGACUUGACCGGGGGCU 20 1830

BCLllA-1445 + ACU UGGACUUGACCGGGGGC 20 1831

BCLllA-1446 + GACUUGGACUUGACCGGGGG 20 1832

BCLllA-1447 + CGCAUGACUUGGACUUGACC 20 1833 BCLllA-1448 + UCGCAUGACUUGGACUUGAC 20 1834

BCLllA-1449 + CUCGCAUGACUUGGACU UGA 20 1835

BCLllA-1450 + UGCCGCAGAACUCGCAUGAC 20 1836

BCLllA-1451 + GAAAUUUGAACGUCUUGCCG 20 1837

BCLllA-1452 + CCACCAGGU UGCUCUGAAAU 20 1838

BCLllA-1453 + CGGUGCACCACCAGGUUGCU 20 1839

BCLllA-1454 + GGUCGCACAGGU UGCACUUG 20 1840

BCLllA-1455 + UGGCGCU UCAGCUUGCUGGC 20 1841

BCLllA-1456 + CGUCGGACU UGACCGUCAUG 20 1842

BCLllA-1457 + UCGUCGGACUUGACCGUCAU 20 1843

BCLllA-1458 + GUCGUCGGACUUGACCGUCA 20 1844

BCLllA-1459 + CGUCGUCGGACUUGACCGUC 20 1845

BCLllA-1460 + UGGCGGUGGAGAGACCGUCG 20 1846

BCLllA-1461 + GU UCCGGGGAGCUGGCGGUG 20 1847

BCLllA-1462 + GGGUUCCGGGGAGCUGGCGG 20 1848

BCLllA-1463 + CGGGU UCCGGGGAGCUGGCG 20 1849

BCLllA-1464 + GUCGCUGGUGCCGGGU UCCG 20 1850

BCLllA-1465 + AGUCGCUGGUGCCGGGUUCC 20 1851

BCLllA-1466 + AAGUCGCUGGUGCCGGGUUC 20 1852

BCLllA-1467 + CAAGUCGCUGGUGCCGGGUU 20 1853

BCLllA-1468 + UGCCCACCAAGUCGCUGGUG 20 1854

BCLllA-1469 + UGAACUUGGCCACCACGGAC 20 1855

BCLllA-1470 + CGCUCUUGAACUUGGCCACC 20 1856

BCLllA-1471 + GGUUGGGGUCGUUCUCGCUC 20 1857

BCLllA-1472 + CCCGUUCUCCGGGAUCAGGU 20 1858

BCLllA-1473 + CCCCGUUCUCCGGGAUCAGG 20 1859

BCLllA-1474 + UCCUCCUCGUCCCCGUUCUC 20 1860

BCLllA-1475 + UUCCUCCUCGUCCCCGUUCU 20 1861

BCLllA-1476 + GCGCCGCCUCCAGGCUCAGC 20 1862

BCLllA-1477 + CACGCCCACGACCGCGCCCC 20 1863

BCLllA-1478 + AUGCCCUGCAUGACGUCGGG 20 1864

BCLllA-1479 + GCACCAUGCCCUGCAUGACG 20 1865

BCLllA-1480 + CGCUGAAGUGCUGCAUGGAG 20 1866

BCLllA-1481 + GGCCUCGCUGAAGUGCUGCA 20 1867

BCLllA-1482 + AGGCCUCGCUGAAGUGCUGC 20 1868

BCLllA-1483 + GGACCUGGUGGAAGGCCUCG 20 1869

BCLllA-1484 + GCUUCUCGCCCAGGACCUGG 20 1870

BCLllA-1485 + UGCUUCUCGCCCAGGACCUG 20 1871

BCLllA-1486 + CCGCGCUUAUGCU UCUCGCC 20 1872

BCLllA-1487 + GCGGUCCGACUCGCCGGCCA 20 1873

BCLllA-1488 + CCCCGAGGCCGACUCGCCCG 20 1874

BCLllA-1489 + CCCCCGAGGCCGACUCGCCC 20 1875 BCLllA-1490 + CCCCCCGAGGCCGACUCGCC 20 1876

BCLllA-1491 + GCCCCCCGAGGCCGACUCGC 20 1877

BCLllA-1492 + CAGCUUUUUGGACAGGCCCC 20 1878

BCLllA-1493 + GGCUGCCCAGCAGCAGCUUU 20 1879

BCLllA-1494 + AGAGAAGGGGCUCAGCGAGC 20 1880

BCLllA-1495 + UAGAGAAGGGGCUCAGCGAG 20 1881

BCLllA-1496 + GCGCUUAGAGAAGGGGCUCA 20 1882

BCLllA-1497 + GAGCUUGAUGCGCUUAGAGA 20 1883

BCLllA-1498 + CGAGCU UGAUGCGCUUAGAG 20 1884

BCLllA-1499 + UCUCGAGCUUGAUGCGCUUA 20 1885

BCLllA-1500 + CUUCUCGAGCUUGAUGCGCU 20 1886

BCLllA-1501 + GGGGCAGGUCGAACUCCUUC 20 1887

BCLllA-1502 + GCAUCGCGGCCGGGGGCAGG 20 1888

BCLllA-1503 + CCGUGUUGGGCAUCGCGGCC 20 1889

BCLllA-1504 + UCCGUGUUGGGCAUCGCGGC 20 1890

BCLllA-1505 + CUCCGUGU UGGGCAUCGCGG 20 1891

BCLllA-1506 + GCGAGUACACGUUCUCCGUG 20 1892

BCLllA-1507 + CGCGUAGCCGGCGAGCCACU 20 1893

BCLllA-1508 + GCCUGGAGGCCGCGUAGCCG 20 1894

BCLllA-1509 + GAAGGGAUCUUUGAGCUGCC 20 1895

BCLllA-1510 + GGAAGGGAUCUUUGAGCUGC 20 1896

BCLllA-1511 + CGAAGCUAAGGAAGGGAUCU 20 1897

BCLllA-1512 + GGAGUCUCCGAAGCUAAGGA 20 1898

BCLllA-1513 + UGGAGUCUCCGAAGCUAAGG 20 1899

BCLllA-1514 + GUCUGGAGUCUCCGAAGCUA 20 1900

BCLllA-1515 + UGUCUGGAGUCUCCGAAGCU 20 1901

BCLllA-1516 + AAGGCGAUUGUCUGGAGUCU 20 1902

BCLllA-1517 + GGAGGCAAAAGGCGAUUGUC 20 1903

BCLllA-1518 + AGGAGGCAAAAGGCGAUUGU 20 1904

BCLllA-1519 + CUCCGAGGAGUGCUCCGACG 20 1905

BCLllA-1520 + UCUCCGAGGAGUGCUCCGAC 20 1906

BCLllA-1521 + GU UCUCCGAGGAGUGCUCCG 20 1907

BCLllA-1522 + GCGCAAACUCCCGUUCUCCG 20 1908

BCLllA-1523 + AGCGCAAACUCCCGUUCUCC 20 1909

BCLllA-1524 + GAAGCGCAAACUCCCGU UCU 20 1910

BCLllA-1525 + CCAGCUCCCCGGGCGGUGUG 20 1911

BCLllA-1526 + GUCCAGCUCCCCGGGCGGUG 20 1912

BCLllA-1527 + CGUCCAGCUCCCCGGGCGGU 20 1913

BCLllA-1528 + AGAUCCCUCCGUCCAGCUCC 20 1914

BCLllA-1529 + ACUUCCCGUGCCGCUGCGCC 20 1915

BCLllA-1530 + CCGGGCCCGGACCACUAAUA 20 1916

BCLllA-1531 + CCCGGGCCCGGACCACUAAU 20 1917 BCLllA-1532 + UGAGCUGGGCCUGCCCGGGC 20 1918

BCLllA-1533 + CUCUUUUGAGCUGGGCCUGC 20 1919

BCLllA-1534 + UGCGUCUGCCCUCUUU UGAG 20 1920

BCLllA-1535 + GUCGCUGCGUCUGCCCUCUU 20 1921

BCLllA-1536 + UUGUACAUGUGUAGCUG 17 1922

BCLllA-1537 + AGAGAAACCAUGCACUG 17 1923

BCLllA-1538 + U UCUGUGCGUGUUGCAA 17 1924

BCLllA-1539 + UGUUCUGUGCGUGUUGC 17 1925

BCLllA-1540 + AAGUAGAUUCUUAAUCC 17 1926

BCLllA-1541 + ACCAACCCGCGGGGUCA 17 1927

BCLllA-1542 + UACCAACCCGCGGGGUC 17 1928

BCLllA-1543 + AUACCAACCCGCGGGGU 17 1929

BCLllA-1544 + GAAGGGAUACCAACCCG 17 1930

BCLllA-1545 + UGAAGGGAUACCAACCC 17 1931

BCLllA-1546 + UCUGCACCUAGUCCUGA 17 1932

BCLllA-1547 + UUCUGCACCUAGUCCUG 17 1933

BCLllA-1548 + ACAUUCUGCACCUAGUC 17 1934

BCLllA-1549 + AUGGAGAGGUGGCUGGG 17 1935

BCLllA-1550 + CCCAUGGAGAGGUGGCU 17 1936

BCLllA-1551 + UCCCAUGGAGAGGUGGC 17 1937

BCLllA-1552 + AUCCCAUGGAGAGGUGG 17 1938

BCLllA-1553 + GCAAUAUGAAUCCCAUG 17 1939

BCLllA-1554 + CUGCAAUAUGAAUCCCA 17 1940

BCLllA-1555 + UCUGCAAUAUGAAUCCC 17 1941

BCLllA-1556 + GGGUUAUUGUCUGCAAU 17 1942

BCLllA-1557 + UAUUCUUAGCAGGUUAA 17 1943

BCLllA-1558 + GUAUUCUUAGCAGGUUA 17 1944

BCLllA-1559 + GCGCCCUUCUGCCAGGC 17 1945

BCLllA-1560 + AGCGCCCUUCUGCCAGG 17 1946

BCLllA-1561 + AACAGGGGGGGAGUGGG 17 1947

BCLllA-1562 + AAACAGGGGGGGAGUGG 17 1948

BCLllA-1563 + GACUAAACAGGGGGGGA 17 1949

BCLllA-1564 + GGUGGACUAAACAGGGG 17 1950

BCLllA-1565 + UGGUGGACUAAACAGGG 17 1951

BCLllA-1566 + GUGGUGGACUAAACAGG 17 1952

BCLllA-1567 + GGUGGUGGACUAAACAG 17 1953

BCLllA-1568 + CGGUGGUGGACUAAACA 17 1954

BCLllA-1569 + UCGGUGGUGGACUAAAC 17 1955

BCLllA-1570 + CUCGGUGGUGGACUAAA 17 1956

BCLllA-1571 + CAAGUGAUGUCUCGGUG 17 1957

BCLllA-1572 + CAGGCGCUCUAUGCGGU 17 1958

BCLllA-1573 + CCAGGCGCUCUAUGCGG 17 1959 BCLllA-1574 + CCCAGGCGCUCUAUGCG 17 1960

BCLllA-1575 + CUCGGGUGAUGGGUGGC 17 1961

BCLllA-1576 + UCAAAGGCACUCGGGUG 17 1962

BCLllA-1577 + CACCCUGUCAAAGGCAC 17 1963

BCLllA-1578 + GGGAGGCUCCAUAGCCA 17 1964

BCLllA-1579 + CUAGAGAAAUCCAUGGC 17 1965

BCLllA-1580 + CCUAGAGAAAUCCAUGG 17 1966

BCLllA-1581 + UCCUAGAGAAAUCCAUG 17 1967

BCLllA-1582 + GCUCUCUAAGUCUCCUA 17 1968

BCLllA-1583 + CAGCUCUCUAAGUCUCC 17 1969

BCLllA-1584 + CCGGCCUGGGGACAGCG 17 1970

BCLllA-1585 + UAGGGCUGGGCCGGCCU 17 1971

BCLllA-1586 + AUAGGGCUGGGCCGGCC 17 1972

BCLllA-1587 + CAUAGGGCUGGGCCGGC 17 1973

BCLllA-1588 + GUAACCUUUGCAUAGGG 17 1974

BCLllA-1589 + U UGCAGUAACCU UUGCA 17 1975

BCLllA-1590 + GCGGCUUGCUACCUGGC 17 1976

BCLllA-1591 + GGCGGCU UGCUACCUGG 17 1977

BCLllA-1592 + GGGGGGGCGUCGCCAGG 17 1978

BCLllA-1593 + GGAGGGGGGGCGUCGCC 17 1979

BCLllA-1594 + GGGAGGGGGGGCGUCGC 17 1980

BCLllA-1595 + AUUGCAGAGGAGGGAGG 17 1981

BCLllA-1596 + GAUUGCAGAGGAGGGAG 17 1982

BCLllA-1597 + GGAUUGCAGAGGAGGGA 17 1983

BCLllA-1598 + CGGAUUGCAGAGGAGGG 17 1984

BCLllA-1599 + GCGGAUUGCAGAGGAGG 17 1985

BCLllA-1600 + GGGCGGAUUGCAGAGGA 17 1986

BCLllA-1601 + GGGGCGGAUUGCAGAGG 17 1987

BCLllA-1602 + AGGGGCGGAUUGCAGAG 17 1988

BCLllA-1603 + GGAGGGGCGGAUUGCAG 17 1989

BCLllA-1604 + AGGAGGGGCGGAUUGCA 17 1990

BCLllA-1605 + GGAGGAGGGGCGGAUUG 17 1991

BCLllA-1606 + GCUGGGAGGGAGGAGGG 17 1992

BCLllA-1607 + GGGGGCUGGGAGGGAGG 17 1993

BCLllA-1608 + CGGGGGCUGGGAGGGAG 17 1994

BCLllA-1609 + ACCGGGGGCUGGGAGGG 17 1995

BCLllA-1610 + GACCGGGGGCUGGGAGG 17 1996

BCLllA-1611 + U UGACCGGGGGCUGGGA 17 1997

BCLllA-1612 + CUUGACCGGGGGCUGGG 17 1998

BCLllA-1613 + ACU UGACCGGGGGCUGG 17 1999

BCLllA-1614 + GGACUUGACCGGGGGCU 17 2000

BCLllA-1615 + UGGACUUGACCGGGGGC 17 2001 BCLllA-1616 + UUGGACUUGACCGGGGG 17 2002

BCLllA-1617 + AUGACUUGGACUUGACC 17 2003

BCLllA-1618 + CAUGACUUGGACUUGAC 17 2004

BCLllA-1619 + GCAUGACUUGGACUUGA 17 2005

BCLllA-1620 + CGCAGAACUCGCAUGAC 17 2006

BCLllA-1621 + AUUUGAACGUCUUGCCG 17 2007

BCLllA-1622 + CCAGGUUGCUCUGAAAU 17 2008

BCLllA-1623 + UGCACCACCAGGUUGCU 17 2009

BCLllA-1624 + CGCACAGGUUGCACUUG 17 2010

BCLllA-1625 + CGCUUCAGCUUGCUGGC 17 2011

BCLllA-1626 + CGGACU UGACCGUCAUG 17 2012

BCLllA-1627 + UCGGACUUGACCGUCAU 17 2013

BCLllA-1628 + GUCGGACUUGACCGUCA 17 2014

BCLllA-1629 + CGUCGGACUUGACCGUC 17 2015

BCLllA-1630 + CGGUGGAGAGACCGUCG 17 2016

BCLllA-1631 + CCGGGGAGCUGGCGGUG 17 2017

BCLllA-1632 + U UCCGGGGAGCUGGCGG 17 2018

BCLllA-1633 + GUUCCGGGGAGCUGGCG 17 2019

BCLllA-1634 + GCUGGUGCCGGGUUCCG 17 2020

BCLllA-1635 + CGCUGGUGCCGGGU UCC 17 2021

BCLllA-1636 + UCGCUGGUGCCGGGUUC 17 2022

BCLllA-1637 + GUCGCUGGUGCCGGGUU 17 2023

BCLllA-1638 + CCACCAAGUCGCUGGUG 17 2024

BCLllA-1639 + ACU UGGCCACCACGGAC 17 2025

BCLllA-1640 + UCUUGAACUUGGCCACC 17 2026

BCLllA-1641 + UGGGGUCGUUCUCGCUC 17 2027

BCLllA-1642 + GUUCUCCGGGAUCAGGU 17 2028

BCLllA-1643 + CGUUCUCCGGGAUCAGG 17 2029

BCLllA-1644 + UCCUCGUCCCCGUUCUC 17 2030

BCLllA-1645 + CUCCUCGUCCCCGU UCU 17 2031

BCLllA-1646 + CCGCCUCCAGGCUCAGC 17 2032

BCLllA-1647 + GCCCACGACCGCGCCCC 17 2033

BCLllA-1648 + CCCUGCAUGACGUCGGG 17 2034

BCLllA-1649 + CCAUGCCCUGCAUGACG 17 2035

BCLllA-1650 + UGAAGUGCUGCAUGGAG 17 2036

BCLllA-1651 + CUCGCUGAAGUGCUGCA 17 2037

BCLllA-1652 + CCUCGCUGAAGUGCUGC 17 2038

BCLllA-1653 + CCUGGUGGAAGGCCUCG 17 2039

BCLllA-1654 + UCUCGCCCAGGACCUGG 17 2040

BCLllA-1655 + UUCUCGCCCAGGACCUG 17 2041

BCLllA-1656 + CGCUUAUGCUUCUCGCC 17 2042

BCLllA-1657 + GUCCGACUCGCCGGCCA 17 2043 BCLllA-1658 + CGAGGCCGACUCGCCCG 17 2044

BCLllA-1659 + CCGAGGCCGACUCGCCC 17 2045

BCLllA-1660 + CCCGAGGCCGACUCGCC 17 2046

BCLllA-1661 + CCCCGAGGCCGACUCGC 17 2047

BCLllA-1662 + CUU UUUGGACAGGCCCC 17 2048

BCLllA-1663 + UGCCCAGCAGCAGCUU U 17 2049

BCLllA-1664 + GAAGGGGCUCAGCGAGC 17 2050

BCLllA-1665 + AGAAGGGGCUCAGCGAG 17 2051

BCLllA-1666 + CUUAGAGAAGGGGCUCA 17 2052

BCLllA-1667 + CUUGAUGCGCUUAGAGA 17 2053

BCLllA-1668 + GCUUGAUGCGCUUAGAG 17 2054

BCLllA-1669 + CGAGCU UGAUGCGCUUA 17 2055

BCLllA-1670 + CUCGAGCU UGAUGCGCU 17 2056

BCLllA-1671 + GCAGGUCGAACUCCUUC 17 2057

BCLllA-1672 + UCGCGGCCGGGGGCAGG 17 2058

BCLllA-1673 + UGUUGGGCAUCGCGGCC 17 2059

BCLllA-1674 + GUGUUGGGCAUCGCGGC 17 2060

BCLllA-1675 + CGUGUUGGGCAUCGCGG 17 2061

BCLllA-1676 + AGUACACGUUCUCCGUG 17 2062

BCLllA-1677 + GUAGCCGGCGAGCCACU 17 2063

BCLllA-1678 + UGGAGGCCGCGUAGCCG 17 2064

BCLllA-1679 + GGGAUCUUUGAGCUGCC 17 2065

BCLllA-1680 + AGGGAUCUUUGAGCUGC 17 2066

BCLllA-1681 + AGCUAAGGAAGGGAUCU 17 2067

BCLllA-1682 + GUCUCCGAAGCUAAGGA 17 2068

BCLllA-1683 + AGUCUCCGAAGCUAAGG 17 2069

BCLllA-1684 + UGGAGUCUCCGAAGCUA 17 2070

BCLllA-1685 + CUGGAGUCUCCGAAGCU 17 2071

BCLllA-1686 + GCGAUUGUCUGGAGUCU 17 2072

BCLllA-1687 + GGCAAAAGGCGAUUGUC 17 2073

BCLllA-1688 + AGGCAAAAGGCGAUUGU 17 2074

BCLllA-1689 + CGAGGAGUGCUCCGACG 17 2075

BCLllA-1690 + CCGAGGAGUGCUCCGAC 17 2076

BCLllA-1691 + CUCCGAGGAGUGCUCCG 17 2077

BCLllA-1692 + CAAACUCCCGUUCUCCG 17 2078

BCLllA-1693 + GCAAACUCCCGUUCUCC 17 2079

BCLllA-1694 + GCGCAAACUCCCGUUCU 17 2080

BCLllA-1695 + GCUCCCCGGGCGGUGUG 17 2081

BCLllA-1696 + CAGCUCCCCGGGCGGUG 17 2082

BCLllA-1697 + CCAGCUCCCCGGGCGGU 17 2083

BCLllA-1698 + UCCCUCCGUCCAGCUCC 17 2084

BCLllA-1699 + UCCCGUGCCGCUGCGCC 17 2085 BCLllA-1700 + GGCCCGGACCACUAAUA 17 2086

BCLllA-1701 + GGGCCCGGACCACUAAU 17 2087

BCLllA-1702 + GCUGGGCCUGCCCGGGC 17 2088

BCLllA-1703 + UUUUGAGCUGGGCCUGC 17 2089

BCLllA-1704 + GUCUGCCCUCU UUUGAG 17 2090

BCLllA-1705 + GCUGCGUCUGCCCUCU U 17 2091

BCLllA-1706 - CCCCCAUUCGGCGUAGUACC 20 2092

BCLllA-1707 - CCCAUUCGGCGUAGUACCCA 20 2093

BCLllA-1708 - CUCAAGAUGUGUGGCAGUUU 20 2094

BCLllA-1709 - AGAUGUGUGGCAGUUUUCGG 20 2095

BCLllA-1710 - GAUGUGUGGCAGUUUUCGGA 20 2096

BCLllA-1711 - GGCAGUUUUCGGAUGGAAGC 20 2097

BCLllA-1712 - CAGU UUUCGGAUGGAAGCUC 20 2098

BCLllA-1713 - CCAUUCGGCGUAGUACC 17 2099

BCLllA-1714 - AUUCGGCGUAGUACCCA 17 2100

BCLllA-1715 - AAGAUGUGUGGCAGUU U 17 2101

BCLllA-1716 - UGUGUGGCAGUUUUCGG 17 2102

BCLllA-1717 - GUGUGGCAGUUU UCGGA 17 2103

BCLllA-1718 - AGUUUUCGGAUGGAAGC 17 2104

BCLllA-1719 - UUUUCGGAUGGAAGCUC 17 2105

BCLllA-1720 + ACGCCGAAUGGGGGUGUGUG 20 2106

BCLllA-1721 + ACUACGCCGAAUGGGGGUGU 20 2107

BCLllA-1722 + CUCUGGGUACUACGCCGAAU 20 2108

BCLllA-1723 + UCUCUGGGUACUACGCCGAA 20 2109

BCLllA-1724 + CUCUCUGGGUACUACGCCGA 20 2110

BCLllA-1725 + UGAGCUCUCUGGGUACUACG 20 2111

BCLllA-1726 + UGCCACACAUCUUGAGCUCU 20 2112

BCLllA-1727 + UCCGAAAACUGCCACACAUC 20 2113

BCLllA-1728 + AAGGGCUCUCGAGCUUCCAU 20 2114

BCLllA-1729 + CCGAAUGGGGGUGUGUG 17 2115

BCLllA-1730 + ACGCCGAAUGGGGGUGU 17 2116

BCLllA-1731 + UGGGUACUACGCCGAAU 17 2117

BCLllA-1732 + CUGGGUACUACGCCGAA 17 2118

BCLllA-1733 + UCUGGGUACUACGCCGA 17 2119

BCLllA-1734 + GCUCUCUGGGUACUACG 17 2120

BCLllA-1735 + CACACAUCUUGAGCUCU 17 2121

BCLllA-1736 + GAAAACUGCCACACAUC 17 2122

BCLllA-1737 + GGCUCUCGAGCUUCCAU 17 2123

Table IF provides exemplary targeting domains for knocking out the BCLllA gene. In an embodiment, the targeting domain is the exact complement of the target domain. Any of the targeting domains in the table can be used with an N. meningitidis Cas9 molecule that gives double stranded cleavage. Any of the targeting domains in the table can be used with an N. meningitidis Cas9 single- strand break nucleases (nickases). In an embodiment, dual targeting is used to create two nicks. When selecting gRNAs for use in a nickase pair, one gRNA targets a domain in the complementary strand and the second gRNA targets a domain in the non- complementary strand, e.g., a gRNA comprising any minus strand targeting domain may be paired any gRNA comprising a plus strand targeting domain targeting the same target position.

Table IF

Table 2A provides exemplary targeting domains for repressing (i.e., knocking down or decreasing) expression of the BCLllA gene by targeting within the lOOObp of sequence 3' of 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. pyogenes eiCas9 molecule to cause a steric block at the target region, e.g., within lOOObp of sequence 3' of the start codon to block transcription resulting in the repression of the BCL11A gene. Alternatively, any of the targeting domains in the table can be used with a S. pyogenes eiCas9 fused to a transcriptional repressor to decrease transcription and therefore downregulate gene expression.

Table 2A

BCLllA-1789 - GGCGCGGGAGGGCAAGCGCG 20 2175

BCLllA-1790 - GGAGGGCAAGCGCGAGGAGC 20 2176

BCLllA-1791 - GCGCGAGGAGCCGGCACAAA 20 2177

BCLllA-1792 - GGAGCCGGCACAAAAGGCAG 20 2178

BCLllA-1793 - GAGCCGGCACAAAAGGCAGC 20 2179

BCLllA-1794 - GCGGGACAAACACCCACCUC 20 2180

BCLllA-1795 - GACAAACACCCACCUCUGGC 20 2181

BCLllA-1796 - CCACCUCUGGCCGGAACAAA 20 2182

BCLllA-1797 - CCUCUGGCCGGAACAAAAGG 20 2183

BCLllA-1798 - G G A ACAAAAG G CGG CAG U G C 20 2184

BCLllA-1799 - GCCGCGUCUCCCGUCCUUCC 20 2185

BCLllA-1800 - UCCCGUCCUUCCCGGUCCCA 20 2186

BCLllA-1801 - CACGGCUCUCCCCGUCGCCG 20 2187

BCLllA-1802 - CGGCCCCUCUCCCGACUCCG 20 2188

BCLllA-1803 - UCUCCCGACUCCGCGGACUC 20 2189

BCLllA-1804 - CUCCGCGGACUCAGGAGCGC 20 2190

BCLllA-1805 - UCCGCGGACUCAGGAGCGCC 20 2191

BCLllA-1806 - CCGCGGACUCAGGAGCGCCG 20 2192

BCLllA-1807 - CGCGGACUCAGGAGCGCCGG 20 2193

BCLllA-1808 - GUGCCACUUUCUCACUAUUG 20 2194

BCLllA-1809 - UGCCACUUUCUCACUAUUGU 20 2195

BCLllA-1810 - GCCACUUUCUCACUAUUGUG 20 2196

BCLllA-1811 - ACACUUGACCGUGAGCGCGC 20 2197

BCLllA-1812 - AGUCUCACCUCUUUUCUCCC 20 2198

BCLllA-1813 - GUCUCACCUCUUUUCUCCCC 20 2199

BCLllA-1814 - CCUACCCCCCCAUUUUCUUA 20 2200

BCLllA-1815 - CCCCAUUUUCUUACGGUGAG 20 2201

BCLllA-1816 - CCCAUUUUCUUACGGUGAGU 20 2202

BCLllA-1817 - CCCCACCAGCUCCCACCCCC 20 2203

BCLllA-1818 - UGUUCAUUAUUUUGCAAAAC 20 2204

BCLllA-1819 - UCAUUAUUUUGCAAAACUGG 20 2205

BCLllA-1820 - CAUUAUUUUGCAAAACUGGC 20 2206

BCLllA-1821 - AUUAUUUUGCAAAACUGGCG 20 2207

BCLllA-1822 - AUUUUGCAAAACUGGCGGGG 20 2208

BCLllA-1823 - UUUUGCAAAACUGGCGGGGC 20 2209

BCLllA-1824 - UUUGCAAAACUGGCGGGGCG 20 2210

BCLllA-1825 - UUGCAAAACUGGCGGGGCGG 20 2211

BCLllA-1826 - UGCAAAACUGGCGGGGCGGG 20 2212

BCLllA-1827 - GCAAAACUGGCGGGGCGGGG 20 2213

BCLllA-1828 - CAAAACUGGCGGGGCGGGGG 20 2214

BCLllA-1829 - CUGGCGGGGCGGGGGGGGAG 20 2215

BCLllA-1830 - U U U CG A A A AG AG AAA U A A AG 20 2216 BCLllA-1831 - CGAAAAGAGAAAUAAAGCGG 20 2217

BCLllA-1832 - AGAGAAAUAAAGCGGCGGAA 20 2218

BCLllA-1833 - G AAA U A A AG CG G CG G A A AG G 20 2219

BCLllA-1834 - AGCGGCGGAAAGGAGGAAAG 20 2220

BCLllA-1835 - GGCGGAAAGGAGGAAAGAGG 20 2221

BCLllA-1836 - UAAAAU U AAAU AAAAU U AAA 20 2222

BCLllA-1837 - CUGUCUCAAAAGUGCAUACA 20 2223

BCLllA-1838 - CAAAAGUGCAUACACGGCAA 20 2224

BCLllA-1839 - UACACGGCAAUGGUUCCAGA 20 2225

BCLllA-1840 - ACACGGCAAUGGUUCCAGAU 20 2226

BCLllA-1841 - CAAUGGUUCCAGAUGGGAUG 20 2227

BCLllA-1842 - AAUGGUUCCAGAUGGGAUGA 20 2228

BCLllA-1843 - AUCUCUUUUACCUCGACUCU 20 2229

BCLllA-1844 - UCUUUUACCUCGACUCUCGG 20 2230

BCLllA-1845 - AUAAUUAUUAUUACUAUUAU 20 2231

BCLllA-1846 - UAAUUAUUAUUACUAU UAUU 20 2232

BCLllA-1847 + UAAUAAUCACGAGAGCGCGC 20 2233

BCLllA-1848 + CAGGACUAGAAGCAAAAGCG 20 2234

BCLllA-1849 + AGGACUAGAAGCAAAAGCGA 20 2235

BCLllA-1850 + GGACUAGAAGCAAAAGCGAG 20 2236

BCLllA-1851 + GACUAGAAGCAAAAGCGAGG 20 2237

BCLllA-1852 + AGCAAAAGCGAGGGGGAGAG 20 2238

BCLllA-1853 + GCAAAAGCGAGGGGGAGAGA 20 2239

BCLllA-1854 + CAAAAGCGAGGGGGAGAGAG 20 2240

BCLllA-1855 + AG AAAAACCU CCG AG AG U CG 20 2241

BCLllA-1856 + AGUCGAGGUAAAAGAGAUAA 20 2242

BCLllA-1857 + GUCGAGGUAAAAGAGAUAAA 20 2243

BCLllA-1858 + U CG AGG U AAAAG AG AU AAAG 20 2244

BCLllA-1859 + CG AG G U A A A AG AG A U A A AG G 20 2245

BCLllA-1860 + GAAAAAACCCUCAUCCCAUC 20 2246

BCLllA-1861 + CUU UAUUUCUCUUU UCGAAA 20 2247

BCLllA-1862 + CAAAAUAAUGAACAAUGCUA 20 2248

BCLllA-1863 + GAACAACUCACAUGCAAACC 20 2249

BCLllA-1864 + AACAACUCACAUGCAAACCU 20 2250

BCLllA-1865 + ACAACUCACAUGCAAACCUG 20 2251

BCLllA-1866 + CAACUCACAUGCAAACCUGG 20 2252

BCLllA-1867 + CUCACAUGCAAACCUGGGGG 20 2253

BCLllA-1868 + UCACAUGCAAACCUGGGGGU 20 2254

BCLllA-1869 + GCAAACCUGGGGGUGGGAGC 20 2255

BCLllA-1870 + AACCUGGGGGUGGGAGCUGG 20 2256

BCLllA-1871 + ACCUGGGGGUGGGAGCUGGU 20 2257

BCLllA-1872 + CCUGGGGGUGGGAGCUGGUG 20 2258 BCLllA-1873 + GGGUGGGAGCUGGUGGGGAA 20 2259

BCLllA-1874 + GGUGGGAGCUGGUGGGGAAA 20 2260

BCLllA-1875 + GGGAGCUGGUGGGGAAAGGG 20 2261

BCLllA-1876 + U CCCACU CACCG U AAG AAAA 20 2262

BCLllA-1877 + CCCACU CACCG U AAG AAAAU 20 2263

BCLllA-1878 + CCACUCACCGUAAGAAAAUG 20 2264

BCLllA-1879 + CACUCACCGUAAGAAAAUGG 20 2265

BCLllA-1880 + ACUCACCGUAAGAAAAUGGG 20 2266

BCLllA-1881 + CUCACCGUAAGAAAAUGGGG 20 2267

BCLllA-1882 + CCGUAAGAAAAUGGGGGGGU 20 2268

BCLllA-1883 + CGUAAGAAAAUGGGGGGGUA 20 2269

BCLllA-1884 + AAGAAAAUGGGGGGGUAGGG 20 2270

BCLllA-1885 + AGAAAAUGGGGGGGUAGGGA 20 2271

BCLllA-1886 + CAAGUCUAAAAAACGAUUCC 20 2272

BCLllA-1887 + AAGUCUAAAAAACGAUUCCC 20 2273

BCLllA-1888 + AGUCUAAAAAACGAUUCCCG 20 2274

BCLllA-1889 + ACGAUUCCCGGGGAGAAAAG 20 2275

BCLllA-1890 + GGGGAGAAAAGAGGUGAGAC 20 2276

BCLllA-1891 + AAAGAGGUGAGACUGGCUUU 20 2277

BCLllA-1892 + U UUGGACACCAGCGCGCUCA 20 2278

BCLllA-1893 + GCUCACGGUCAAGUGUGCAG 20 2279

BCLllA-1894 + CUCACGGUCAAGUGUGCAGC 20 2280

BCLllA-1895 + ACGGUCAAGUGUGCAGCGGG 20 2281

BCLllA-1896 + UCCCCACAAUAGUGAGAAAG 20 2282

BCLllA-1897 + AUAGUGAGAAAGUGGCACUG 20 2283

BCLllA-1898 + GAGAAAGUGGCACUGUGGAA 20 2284

BCLllA-1899 + AGAAAGUGGCACUGUGGAAA 20 2285

BCLllA-1900 + GAAAGUGGCACUGUGGAAAG 20 2286

BCLllA-1901 + GCACUGUGGAAAGGGGCCCC 20 2287

BCLllA-1902 + CCCCGGCGCUCCUGAGUCCG 20 2288

BCLllA-1903 + CGCUCCUGAGUCCGCGGAGU 20 2289

BCLllA-1904 + GCUCCUGAGUCCGCGGAGUC 20 2290

BCLllA-1905 + UGAGUCCGCGGAGUCGGGAG 20 2291

BCLllA-1906 + GAGUCCGCGGAGUCGGGAGA 20 2292

BCLllA-1907 + AGUCCGCGGAGUCGGGAGAG 20 2293

BCLllA-1908 + CGGAGUCGGGAGAGGGGCCG 20 2294

BCLllA-1909 + CGGGAGAGGGGCCGCGGCGA 20 2295

BCLllA-1910 + GGGAGAGGGGCCGCGGCGAC 20 2296

BCLllA-1911 + GGAGAGGGGCCGCGGCGACG 20 2297

BCLllA-1912 + CGCGGCGACGGGGAGAGCCG 20 2298

BCLllA-1913 + GCGGCGACGGGGAGAGCCGU 20 2299

BCLllA-1914 + GACGGGGAGAGCCGUGGGAC 20 2300 BCLllA-1915 + ACGGGGAGAGCCGUGGGACC 20 2301

BCLllA-1916 + GGAGAGCCGUGGGACCGGGA 20 2302

BCLllA-1917 + AGCCGUGGGACCGGGAAGGA 20 2303

BCLllA-1918 + GCCGUGGGACCGGGAAGGAC 20 2304

BCLllA-1919 + ACCGGGAAGGACGGGAGACG 20 2305

BCLllA-1920 + GGAAGGACGGGAGACGCGGC 20 2306

BCLllA-1921 + GGCACUGCCGCCUU UUGUUC 20 2307

BCLllA-1922 + CCGCCUUUUGUUCCGGCCAG 20 2308

BCLllA-1923 + CCUU UUGUUCCGGCCAGAGG 20 2309

BCLllA-1924 + CUU UUGUUCCGGCCAGAGGU 20 2310

BCLllA-1925 + UGUCCCGCUGCCU UUUGUGC 20 2311

BCLllA-1926 + GCCGCCGCCGCCGCCGCCGA 20 2312

BCLllA-1927 + CCGCCGCCGCCGCCGCCGAA 20 2313

BCLllA-1928 + CGCCGCCGCCGCCGAAGGGC 20 2314

BCLllA-1929 + GCCGCCGAAGGGCAGGAGCU 20 2315

BCLllA-1930 + CCGCCGAAGGGCAGGAGCUA 20 2316

BCLllA-1931 + CGAAGGGCAGGAGCUAGGGC 20 2317

BCLllA-1932 + GAAGGGCAGGAGCUAGGGCC 20 2318

BCLllA-1933 + AAGGGCAGGAGCUAGGGCCG 20 2319

BCLllA-1934 + AGGGCAGGAGCUAGGGCCGG 20 2320

BCLllA-1935 + GCAGGAGCUAGGGCCGGGGG 20 2321

BCLllA-1936 + GGAGCUAGGGCCGGGGGAGG 20 2322

BCLllA-1937 + GCUAGGGCCGGGGGAGGAGG 20 2323

BCLllA-1938 + GGGCCGGGGGAGGAGGCGGC 20 2324

BCLllA-1939 + GGCCGGGGGAGGAGGCGGCC 20 2325

BCLllA-1940 + GCCGGGGGAGGAGGCGGCCG 20 2326

BCLllA-1941 + CCGGGGGAGGAGGCGGCCGG 20 2327

BCLllA-1942 + AGGAGGCGGCCGGGGGCACG 20 2328

BCLllA-1943 + GGAGGCGGCCGGGGGCACGC 20 2329

BCLllA-1944 + CGGCCGGGGGCACGCGGGAG 20 2330

BCLllA-1945 + GGCCGGGGGCACGCGGGAGA 20 2331

BCLllA-1946 + CGGGGGCACGCGGGAGAGGG 20 2332

BCLllA-1947 + GGGGGCACGCGGGAGAGGGA 20 2333

BCLllA-1948 + GGCACGCGGGAGAGGGAGGG 20 2334

BCLllA-1949 + GCACGCGGGAGAGGGAGGGA 20 2335

BCLllA-1950 + GGAGAGGGAGGGAGGGAGCC 20 2336

BCLllA-1951 + GAGCCCGGACUGCUGCCUCC 20 2337

BCLllA-1952 + AGCCCGGACUGCUGCCUCCU 20 2338

BCLllA-1953 + CCCUCCCGACCGAACCUCAG 20 2339

BCLllA-1954 + ACCGAACCUCAGAGGCAGCA 20 2340

BCLllA-1955 + AGAGGCAGCAAGGAGAAGAC 20 2341

BCLllA-1956 + A A A A U A A A A U AAA U A A AAC A 20 2342 BCLllA-1957 - UCUCCUUGCUGCCUCUG 17 2343

BCLllA-1958 - UUGCUGCCUCUGAGGUU 17 2344

BCLllA-1959 - UGCCUCUGAGGUUCGGU 17 2345

BCLllA-1960 - GCCUCUGAGGUUCGGUC 17 2346

BCLllA-1961 - UCUGAGGUUCGGUCGGG 17 2347

BCLllA-1962 - CUGAGGUUCGGUCGGGA 17 2348

BCLllA-1963 - UGAGGUUCGGUCGGGAG 17 2349

BCLllA-1964 - GGUUCGGUCGGGAGGGG 17 2350

BCLllA-1965 - GUUCGGUCGGGAGGGGA 17 2351

BCLllA-1966 - UCGGGAGGGGAGGGCAG 17 2352

BCLllA-1967 - GAGGGCAGCGGCAACCC 17 2353

BCLllA-1968 - GGCAGCGGCAACCCAGG 17 2354

BCLllA-1969 - CCCAG G AG G CAG C AG U C 17 2355

BCLllA-1970 - CCAGGAGGCAGCAGUCC 17 2356

BCLllA-1971 - CCUCUCCCGCGUGCCCC 17 2357

BCLllA-1972 - CCGGCCGCCUCCUCCCC 17 2358

BCLllA-1973 - CCCUAGCUCCUGCCCUU 17 2359

BCLllA-1974 - UAGCUCCUGCCCUUCGG 17 2360

BCLllA-1975 - CUCCUGCCCUUCGGCGG 17 2361

BCLllA-1976 - CUGCCCUUCGGCGGCGG 17 2362

BCLllA-1977 - CCCUUCGGCGGCGGCGG 17 2363

BCLllA-1978 - UUCGGCGGCGGCGGCGG 17 2364

BCLllA-1979 - GGCGGCGGCGGCGGCGG 17 2365

BCLllA-1980 - CGGCGGCGGCGGCGGCG 17 2366

BCLllA-1981 - GGCGGCGGCGGCGGCGC 17 2367

BCLllA-1982 - GGCGGCGGCGGCGCGGG 17 2368

BCLllA-1983 - GCGGCGGCGGCGCGGGA 17 2369

BCLllA-1984 - GCGGGAGGGCAAGCGCG 17 2370

BCLllA-1985 - GGGCAAGCGCGAGGAGC 17 2371

BCLllA-1986 - CGAGGAGCCGGCACAAA 17 2372

BCLllA-1987 - G CCGG CAC AAAAG G CAG 17 2373

BCLllA-1988 - CCGGCACAAAAGGCAGC 17 2374

BCLllA-1989 - GGACAAACACCCACCUC 17 2375

BCLllA-1990 - AAACACCCACCUCUGGC 17 2376

BCLllA-1991 - CCUCUGGCCGGAACAAA 17 2377

BCLllA-1992 - C U GG CCG G A ACAAAAG G 17 2378

BCLllA-1993 - A C A A A AG GCGGCAGUGC 17 2379

BCLllA-1994 - GCGUCUCCCGUCCUUCC 17 2380

BCLllA-1995 - CGUCCUUCCCGGUCCCA 17 2381

BCLllA-1996 - GGCUCUCCCCGUCGCCG 17 2382

BCLllA-1997 - CCCCUCUCCCGACUCCG 17 2383

BCLllA-1998 - CCCGACUCCGCGGACUC 17 2384 BCLllA-1999 - CGCGGACUCAGGAGCGC 17 2385

BCLllA-2000 - GCGGACUCAGGAGCGCC 17 2386

BCLllA-2001 - CGGACUCAGGAGCGCCG 17 2387

BCLllA-2002 - GGACUCAGGAGCGCCGG 17 2388

BCLllA-2003 - CCACUUUCUCACUAUUG 17 2389

BCLllA-2004 - CACUUUCUCACUAUUGU 17 2390

BCLllA-2005 - ACUUUCUCACUAUUGUG 17 2391

BCLllA-2006 - CUUGACCGUGAGCGCGC 17 2392

BCLllA-2007 - CUCACCUCUUUUCUCCC 17 2393

BCLllA-2008 - UCACCUCUUUUCUCCCC 17 2394

BCLllA-2009 - ACCCCCCCAUUUUCUUA 17 2395

BCLllA-2010 - CAUUUUCUUACGGUGAG 17 2396

BCLllA-2011 - AUUUUCUUACGGUGAGU 17 2397

BCLllA-2012 - CACCAGCUCCCACCCCC 17 2398

BCLllA-2013 - U CAU U AU U U UG CAAAAC 17 2399

BCLllA-2014 - UUAUUUUGCAAAACUGG 17 2400

BCLllA-2015 - UAUUUUGCAAAACUGGC 17 2401

BCLllA-2016 - AUUUUGCAAAACUGGCG 17 2402

BCLllA-2017 - UUGCAAAACUGGCGGGG 17 2403

BCLllA-2018 - UGCAAAACUGGCGGGGC 17 2404

BCLllA-2019 - GCAAAACUGGCGGGGCG 17 2405

BCLllA-2020 - CAAAACUGGCGGGGCGG 17 2406

BCLllA-2021 - AAAACUGGCGGGGCGGG 17 2407

BCLllA-2022 - AAACUGGCGGGGCGGGG 17 2408

BCLllA-2023 - AACUGGCGGGGCGGGGG 17 2409

BCLllA-2024 - GCGGGGCGGGGGGGGAG 17 2410

BCLllA-2025 - CG A A A AG AG A A A U A A AG 17 2411

BCLllA-2026 - AAAGAGAAAUAAAGCGG 17 2412

BCLllA-2027 - G AAA U A A AG CG G CG G A A 17 2413

BCLllA-2028 - A U A A AG CG G CG G A A AG G 17 2414

BCLllA-2029 - GGCGGAAAGGAGGAAAG 17 2415

BCLllA-2030 - GGAAAGGAGGAAAGAGG 17 2416

BCLllA-2031 - AAU U AAAU AAAAU U AAA 17 2417

BCLllA-2032 - U C U C A A A AG U G C A U AC A 17 2418

BCLllA-2033 - AAGUGCAUACACGGCAA 17 2419

BCLllA-2034 - ACGGCAAUGGUUCCAGA 17 2420

BCLllA-2035 - CGGCAAUGGUUCCAGAU 17 2421

BCLllA-2036 - UGGUUCCAGAUGGGAUG 17 2422

BCLllA-2037 - GGUUCCAGAUGGGAUGA 17 2423

BCLllA-2038 - UCUUUUACCUCGACUCU 17 2424

BCLllA-2039 - UUUACCUCGACUCUCGG 17 2425

BCLllA-2040 - AUUAUUAUUACUAUUAU 17 2426 BCLllA-2041 - U UAUUAUUACUAUUAU U 17 2427

BCLllA-2042 + UAAUCACGAGAGCGCGC 17 2428

BCLllA-2043 + G ACU AG AAG CAAAAG CG 17 2429

BCLllA-2044 + ACU AG AAG CAAAAG CG A 17 2430

BCLllA-2045 + CUAGAAGCAAAAGCGAG 17 2431

BCLllA-2046 + U AG AAG CAAAAG CG AGG 17 2432

BCLllA-2047 + AAAAGCGAGGGGGAGAG 17 2433

BCLllA-2048 + AAAGCGAGGGGGAGAGA 17 2434

BCLllA-2049 + AAGCGAGGGGGAGAGAG 17 2435

BCLllA-2050 + AAAACCU CCG AG AG U CG 17 2436

BCLllA-2051 + CG AG G U A A A AG AG A U A A 17 2437

BCLllA-2052 + G AGG U AAAAG AG AU AAA 17 2438

BCLllA-2053 + AG G U A A A AG AG A U A A AG 17 2439

BCLllA-2054 + G G U A A A AG AG A U A A AG G 17 2440

BCLllA-2055 + AAAACCCUCAUCCCAUC 17 2441

BCLllA-2056 + UAUUUCUCUUUUCGAAA 17 2442

BCLllA-2057 + AAUAAUGAACAAUGCUA 17 2443

BCLllA-2058 + CAACUCACAUGCAAACC 17 2444

BCLllA-2059 + AAC U CAC AU G CAAACCU 17 2445

BCLllA-2060 + ACUCACAUGCAAACCUG 17 2446

BCLllA-2061 + CUCACAUGCAAACCUGG 17 2447

BCLllA-2062 + ACAUGCAAACCUGGGGG 17 2448

BCLllA-2063 + CAUGCAAACCUGGGGGU 17 2449

BCLllA-2064 + AACCUGGGGGUGGGAGC 17 2450

BCLllA-2065 + CUGGGGGUGGGAGCUGG 17 2451

BCLllA-2066 + UGGGGGUGGGAGCUGGU 17 2452

BCLllA-2067 + GGGGGUGGGAGCUGGUG 17 2453

BCLllA-2068 + UGGGAGCUGGUGGGGAA 17 2454

BCLllA-2069 + GGGAGCUGGUGGGGAAA 17 2455

BCLllA-2070 + AGCUGGUGGGGAAAGGG 17 2456

BCLllA-2071 + CACU CACCG U AAG AAAA 17 2457

BCLllA-2072 + ACUCACCGUAAGAAAAU 17 2458

BCLllA-2073 + CUCACCGUAAGAAAAUG 17 2459

BCLllA-2074 + U C A CCG U A AG AAAA U G G 17 2460

BCLllA-2075 + CACCG U AAG AAAAUGGG 17 2461

BCLllA-2076 + ACCGUAAGAAAAUGGGG 17 2462

BCLllA-2077 + UAAGAAAAUGGGGGGGU 17 2463

BCLllA-2078 + AAGAAAAUGGGGGGGUA 17 2464

BCLllA-2079 + AAAAUGGGGGGGUAGGG 17 2465

BCLllA-2080 + AAAUGGGGGGGUAGGGA 17 2466

BCLllA-2081 + GUCUAAAAAACGAUUCC 17 2467

BCLllA-2082 + U CU AAAAAACG AU U CCC 17 2468 BCLllA-2083 + CUAAAAAACGAUUCCCG 17 2469

BCLllA-2084 + AUUCCCGGGGAGAAAAG 17 2470

BCLllA-2085 + GAGAAAAGAGGUGAGAC 17 2471

BCLllA-2086 + GAGGUGAGACUGGCU UU 17 2472

BCLllA-2087 + GGACACCAGCGCGCUCA 17 2473

BCLllA-2088 + C ACG G U CAAG U G U G C AG 17 2474

BCLllA-2089 + ACGGUCAAGUGUGCAGC 17 2475

BCLllA-2090 + GUCAAGUGUGCAGCGGG 17 2476

BCLllA-2091 + CCACAAUAGUGAGAAAG 17 2477

BCLllA-2092 + GUGAGAAAGUGGCACUG 17 2478

BCLllA-2093 + AAAGUGGCACUGUGGAA 17 2479

BCLllA-2094 + AAGUGGCACUGUGGAAA 17 2480

BCLllA-2095 + AGUGGCACUGUGGAAAG 17 2481

BCLllA-2096 + CUGUGGAAAGGGGCCCC 17 2482

BCLllA-2097 + CGGCGCUCCUGAGUCCG 17 2483

BCLllA-2098 + UCCUGAGUCCGCGGAGU 17 2484

BCLllA-2099 + CCUGAGUCCGCGGAGUC 17 2485

BCLllA-2100 + GUCCGCGGAGUCGGGAG 17 2486

BCLllA-2101 + UCCGCGGAGUCGGGAGA 17 2487

BCLllA-2102 + CCGCGGAGUCGGGAGAG 17 2488

BCLllA-2103 + AGUCGGGAGAGGGGCCG 17 2489

BCLllA-2104 + GAGAGGGGCCGCGGCGA 17 2490

BCLllA-2105 + AGAGGGGCCGCGGCGAC 17 2491

BCLllA-2106 + GAGGGGCCGCGGCGACG 17 2492

BCLllA-2107 + GGCGACGGGGAGAGCCG 17 2493

BCLllA-2108 + GCGACGGGGAGAGCCGU 17 2494

BCLllA-2109 + GGGGAGAGCCGUGGGAC 17 2495

BCLllA-2110 + GGGAGAGCCGUGGGACC 17 2496

BCLllA-2111 + GAGCCGUGGGACCGGGA 17 2497

BCLllA-2112 + CGUGGGACCGGGAAGGA 17 2498

BCLllA-2113 + GUGGGACCGGGAAGGAC 17 2499

BCLllA-2114 + GGGAAGGACGGGAGACG 17 2500

BCLllA-2115 + AGGACGGGAGACGCGGC 17 2501

BCLllA-2116 + ACUGCCGCCUU UUGUUC 17 2502

BCLllA-2117 + CCUU UUGUUCCGGCCAG 17 2503

BCLllA-2118 + U UUGUUCCGGCCAGAGG 17 2504

BCLllA-2119 + U UGUUCCGGCCAGAGGU 17 2505

BCLllA-2120 + CCCGCUGCCUUUUGUGC 17 2506

BCLllA-2121 + GCCGCCGCCGCCGCCGA 17 2507

BCLllA-2122 + CCGCCGCCGCCGCCGAA 17 2508

BCLllA-2123 + CGCCGCCGCCGAAGGGC 17 2509

BCLllA-2124 + GCCGAAGGGCAGGAGCU 17 2510 BCLllA-2125 + CCGAAGGGCAGGAGCUA 17 2511

BCLllA-2126 + AGGGCAGGAGCUAGGGC 17 2512

BCLllA-2127 + GGGCAGGAGCUAGGGCC 17 2513

BCLllA-2128 + GGCAGGAGCUAGGGCCG 17 2514

BCLllA-2129 + GCAGGAGCUAGGGCCGG 17 2515

BCLllA-2130 + GGAGCUAGGGCCGGGGG 17 2516

BCLllA-2131 + GCUAGGGCCGGGGGAGG 17 2517

BCLllA-2132 + AGGGCCGGGGGAGGAGG 17 2518

BCLllA-2133 + CCGGGGGAGGAGGCGGC 17 2519

BCLllA-2134 + CGGGGGAGGAGGCGGCC 17 2520

BCLllA-2135 + GGGGGAGGAGGCGGCCG 17 2521

BCLllA-2136 + GGGGAGGAGGCGGCCGG 17 2522

BCLllA-2137 + AGGCGGCCGGGGGCACG 17 2523

BCLllA-2138 + GGCGGCCGGGGGCACGC 17 2524

BCLllA-2139 + CCGGGGGCACGCGGGAG 17 2525

BCLllA-2140 + CGGGGGCACGCGGGAGA 17 2526

BCLllA-2141 + GGGCACGCGGGAGAGGG 17 2527

BCLllA-2142 + GGCACGCGGGAGAGGGA 17 2528

BCLllA-2143 + ACGCGGGAGAGGGAGGG 17 2529

BCLllA-2144 + CGCGGGAGAGGGAGGGA 17 2530

BCLllA-2145 + GAGGGAGGGAGGGAGCC 17 2531

BCLllA-2146 + CCCGGACUGCUGCCUCC 17 2532

BCLllA-2147 + CCGGACUGCUGCCUCCU 17 2533

BCLllA-2148 + UCCCGACCGAACCUCAG 17 2534

BCLllA-2149 + G AACCU CAG AGG CAG CA 17 2535

BCLllA-2150 + G G CAG CAAG G AG AAG AC 17 2536

BCLllA-2151 + AUAAAAUAAAUAAAACA 17 2537

Table 2B provides exemplary targeting domains for repressing (i.e., knocking down or decreasing) expression of the BCLllA gene by targeting within the lOOObp of sequence 3' of 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 eiCas9 molecule to cause a steric block at the target region, e.g., within lOOObp of sequence 3' of the start codon to block transcription resulting in the repression of the BCLllA gene. Alternatively, any of the targeting domains in the table can be used with a S. aureus eiCas9 fused to a transcriptional repressor to decrease transcription and therefore downregulate gene expression.

Table 2B S. aureus gRNA targets for BCLllA knockdown

DNA Target Site SEQ ID gRNA Name Targeting Domain

Strand Length NO

BCLllA-2152 - CAGUCUUCUCCU UGCUGCCU 20 2138

BCLllA-2153 - U UGCUGCCUCUGAGGU UCGG 20 2139

BCLllA-2154 - UGCUGCCUCUGAGGUUCGGU 20 2140

BCLllA-2155 - GCUGCCUCUGAGGUUCGGUC 20 2141

BCLllA-2156 - UGCCUCUGAGGUUCGGUCGG 20 2142

BCLllA-2157 - GCCUCUGAGGUUCGGUCGGG 20 2143

BCLllA-2158 - CCUCUGAGGUUCGGUCGGGA 20 2144

BCLllA-2159 - CUCUGAGGUUCGGUCGGGAG 20 2145

BCLllA-2160 - CUGAGGUUCGGUCGGGAGGG 20 2146

BCLllA-2161 - AGGGGAGGGCAGCGGCAACC 20 2147

BCLllA-2162 - GGGGAGGGCAGCGGCAACCC 20 2148

BCLllA-2163 - GCAACCCAGGAGGCAGCAGU 20 2149

BCLllA-2164 - GCGGCGGCGGCGGCGGCGGC 20 2150

BCLllA-2165 - CGGCGGCGGCGGCGGCGGCG 20 2151

BCLllA-2166 - GGCGGCGGCGGCGGCGGCGC 20 2152

BCLllA-2167 - CGGCGGCGGCGGCGGCGCGG 20 2153

BCLllA-2168 - GGCGGCGCGGGAGGGCAAGC 20 2154

BCLllA-2169 - CGGCGCGGGAGGGCAAGCGC 20 2155

BCLllA-2170 - GGCGCGGGAGGGCAAGCGCG 20 2156

BCLllA-2171 - AGGAGCCGGCACAAAAGGCA 20 2157

BCLllA-2172 - GGAGCCGGCACAAAAGGCAG 20 2158

BCLllA-2173 - GGACAAACACCCACCUCUGG 20 2159

BCLllA-2174 - GACAAACACCCACCUCUGGC 20 2160

BCLllA-2175 - GCGGCCCCUCUCCCGACUCC 20 2161

BCLllA-2176 - CUCUCCCGACUCCGCGGACU 20 2162

BCLllA-2177 - UCUCCCGACUCCGCGGACUC 20 2163

BCLllA-2178 - ACUCCGCGGACUCAGGAGCG 20 2164

BCLllA-2179 - CUCCGCGGACUCAGGAGCGC 20 2165

BCLllA-2180 - UCCGCGGACUCAGGAGCGCC 20 2166

BCLllA-2181 - AGUGCCACUU UCUCACUAUU 20 2167

BCLllA-2182 - GUGCCACU UUCUCACUAUUG 20 2168

BCLllA-2183 - UGCCACUU UCUCACUAUUGU 20 2169

BCLllA-2184 - CUCCCGCUGCACACUUGACC 20 2170

BCLllA-2185 - CAGUCUCACCUCUUUUCUCC 20 2171

BCLllA-2186 - AGUCUCACCUCUUU UCUCCC 20 2172

BCLllA-2187 - GUCUCACCUCUU UUCUCCCC 20 2173

BCLllA-2188 - UACCCCCCCAUUU UCUUACG 20 2174

BCLllA-2189 - CCCCCAUUUUCUUACGGUGA 20 2175

BCLllA-2190 - CCCCAUU UUCUUACGGUGAG 20 2176 BCLllA-2191 - CCCAUUUUCUUACGGUGAGU 20 2177

BCLllA-2192 - UCCCACCCCCAGGUUUGCAU 20 2178

BCLllA-2193 - UUCAUUAUUUUGCAAAACUG 20 2179

BCLllA-2194 - UCAUUAUUUUGCAAAACUGG 20 2180

BCLllA-2195 - UAUUUUGCAAAACUGGCGGG 20 2181

BCLllA-2196 - AUUUUGCAAAACUGGCGGGG 20 2182

BCLllA-2197 - UUUUGCAAAACUGGCGGGGC 20 2183

BCLllA-2198 - UUUGCAAAACUGGCGGGGCG 20 2184

BCLllA-2199 - UUGCAAAACUGGCGGGGCGG 20 2185

BCLllA-2200 - UGCAAAACUGGCGGGGCGGG 20 2186

BCLllA-2201 - GCAAAACUGGCGGGGCGGGG 20 2187

BCLllA-2202 - CAAAACUGGCGGGGCGGGGG 20 2188

BCLllA-2203 - ACUGGCGGGGCGGGGGGGGA 20 2189

BCLllA-2204 - CUGGCGGGGCGGGGGGGGAG 20 2190

BCLllA-2205 - UGGAAUCAUUGCAUUCCUUU 20 2191

BCLllA-2206 - UCAUUGCAUUCCUUUUCGAA 20 2192

BCLllA-2207 - AUUGCAUUCCUUUUCGAAAA 20 2193

BCLllA-2208 - UCGAAAAGAGAAAUAAAGCG 20 2194

BCLllA-2209 - CGAAAAGAGAAAUAAAGCGG 20 2195

BCLllA-2210 - AAGAGAAAUAAAGCGGCGGA 20 2196

BCLllA-2211 - AGAGAAAUAAAGCGGCGGAA 20 2197

BCLllA-2212 - AGAAAUAAAGCGGCGGAAAG 20 2198

BCLllA-2213 - G AAA U A A AG CG G CG G A A AG G 20 2199

BCLllA-2214 - UAAAGCGGCGGAAAGGAGGA 20 2200

BCLllA-2215 - AAGCGGCGGAAAGGAGGAAA 20 2201

BCLllA-2216 - AGCGGCGGAAAGGAGGAAAG 20 2202

BCLllA-2217 - CGGCGGAAAGGAGGAAAGAG 20 2203

BCLllA-2218 - GGCGGAAAGGAGGAAAGAGG 20 2204

BCLllA-2219 - AUACACGGCAAUGGUUCCAG 20 2205

BCLllA-2220 - UACACGGCAAUGGUUCCAGA 20 2206

BCLllA-2221 - CGGCAAUGGUUCCAGAUGGG 20 2207

BCLllA-2222 - GCAAUGGUUCCAGAUGGGAU 20 2208

BCLllA-2223 - UAUCUCUUUUACCUCGACUC 20 2209

BCLllA-2224 - AUCUCUUUUACCUCGACUCU 20 2210

BCLllA-2225 - GACUCUCGGAGGUUUUUCUC 20 2211

BCLllA-2226 - AAUAAUUAUUAUUACUAUUA 20 2212

BCLllA-2227 - ACUAUUAUUGGGUUACUUAC 20 2213

BCLllA-2228 - UAUUAUUGGGUUACUUACGC 20 2214

BCLllA-2229 - UCUUCUCCUUGCUGCCU 17 2215

BCLllA-2230 - CUGCCUCUGAGGUUCGG 17 2216

BCLllA-2231 - UGCCUCUGAGGUUCGGU 17 2217

BCLllA-2232 - GCCUCUGAGGUUCGGUC 17 2218 BCLllA-2233 - CUCUGAGGUUCGGUCGG 17 2219

BCLllA-2234 - UCUGAGGUUCGGUCGGG 17 2220

BCLllA-2235 - CUGAGGUUCGGUCGGGA 17 2221

BCLllA-2236 - UGAGGUUCGGUCGGGAG 17 2222

BCLllA-2237 - AGGUUCGGUCGGGAGGG 17 2223

BCLllA-2238 - GGAGGGCAGCGGCAACC 17 2224

BCLllA-2239 - GAGGGCAGCGGCAACCC 17 2225

BCLllA-2240 - ACCCAGGAGGCAGCAGU 17 2226

BCLllA-2241 - GCGGCGGCGGCGGCGGC 17 2227

BCLllA-2242 - CGGCGGCGGCGGCGGCG 17 2228

BCLllA-2243 - GGCGGCGGCGGCGGCGC 17 2229

BCLllA-2244 - CGGCGGCGGCGGCGCGG 17 2230

BCLllA-2245 - GGCGCGGGAGGGCAAGC 17 2231

BCLllA-2246 - CGCGGGAGGGCAAGCGC 17 2232

BCLllA-2247 - GCGGGAGGGCAAGCGCG 17 2233

BCLllA-2248 - AG CCGG CAC AAAAG G C A 17 2234

BCLllA-2249 - G CCGG CAC AAAAG G C AG 17 2235

BCLllA-2250 - CAAACACCCACCUCUGG 17 2236

BCLllA-2251 - AAACACCCACCUCUGGC 17 2237

BCLllA-2252 - GCCCCUCUCCCGACUCC 17 2238

BCLllA-2253 - UCCCGACUCCGCGGACU 17 2239

BCLllA-2254 - CCCGACUCCGCGGACUC 17 2240

BCLllA-2255 - CCGCGGACUCAGGAGCG 17 2241

BCLllA-2256 - CGCGGACUCAGGAGCGC 17 2242

BCLllA-2257 - GCGGACUCAGGAGCGCC 17 2243

BCLllA-2258 - GCCACUUUCUCACUAUU 17 2244

BCLllA-2259 - CCACUUUCUCACUAUUG 17 2245

BCLllA-2260 - CACUUUCUCACUAUUGU 17 2246

BCLllA-2261 - CCGCUGCACACUUGACC 17 2247

BCLllA-2262 - UCUCACCUCUUUUCUCC 17 2248

BCLllA-2263 - CUCACCUCUUUUCUCCC 17 2249

BCLllA-2264 - UCACCUCUUUUCUCCCC 17 2250

BCLllA-2265 - CCCCCCAUUUUCUUACG 17 2251

BCLllA-2266 - CCAUUUUCUUACGGUGA 17 2252

BCLllA-2267 - CAUUUUCUUACGGUGAG 17 2253

BCLllA-2268 - AUUUUCUUACGGUGAGU 17 2254

BCLllA-2269 - CACCCCCAGGUUUGCAU 17 2255

BCLllA-2270 - AUUAUUUUGCAAAACUG 17 2256

BCLllA-2271 - UUAUUUUGCAAAACUGG 17 2257

BCLllA-2272 - UUUGCAAAACUGGCGGG 17 2258

BCLllA-2273 - UUGCAAAACUGGCGGGG 17 2259

BCLllA-2274 - UGCAAAACUGGCGGGGC 17 2260 BCLllA-2275 - GCAAAACUGGCGGGGCG 17 2261

BCLllA-2276 - CAAAACUGGCGGGGCGG 17 2262

BCLllA-2277 - AAAACUGGCGGGGCGGG 17 2263

BCLllA-2278 - AAACUGGCGGGGCGGGG 17 2264

BCLllA-2279 - AACUGGCGGGGCGGGGG 17 2265

BCLllA-2280 - GGCGGGGCGGGGGGGGA 17 2266

BCLllA-2281 - GCGGGGCGGGGGGGGAG 17 2267

BCLllA-2282 - AAUCAUUGCAUUCCUUU 17 2268

BCLllA-2283 - UUGCAUUCCUUUUCGAA 17 2269

BCLllA-2284 - GCAUUCCUUUUCGAAAA 17 2270

BCLllA-2285 - A A A AG AG A A A U A A AG CG 17 2271

BCLllA-2286 - AAAGAGAAAUAAAGCGG 17 2272

BCLllA-2287 - AGAAAUAAAGCGGCGGA 17 2273

BCLllA-2288 - G AAA U A A AG CG G CG G A A 17 2274

BCLllA-2289 - AAUAAAGCGGCGGAAAG 17 2275

BCLllA-2290 - A U A A AG CG G CG G A A AG G 17 2276

BCLllA-2291 - AGCGGCGGAAAGGAGGA 17 2277

BCLllA-2292 - CGGCGGAAAGGAGGAAA 17 2278

BCLllA-2293 - GGCGGAAAGGAGGAAAG 17 2279

BCLllA-2294 - CGGAAAGGAGGAAAGAG 17 2280

BCLllA-2295 - GGAAAGGAGGAAAGAGG 17 2281

BCLllA-2296 - CACGGCAAUGGUUCCAG 17 2282

BCLllA-2297 - ACGGCAAUGGUUCCAGA 17 2283

BCLllA-2298 - CAAUGGUUCCAGAUGGG 17 2284

BCLllA-2299 - AUGGUUCCAGAUGGGAU 17 2285

BCLllA-2300 - CUCUUUUACCUCGACUC 17 2286

BCLllA-2301 - UCUUUUACCUCGACUCU 17 2287

BCLllA-2302 - UCUCGGAGGUUUUUCUC 17 2288

BCLllA-2303 - AAUUAUUAUUACUAUUA 17 2289

BCLllA-2304 - AUUAUUGGGUUACUUAC 17 2290

BCLllA-2305 - UAUUGGGUUACUUACGC 17 2291

BCLllA-2306 + CGAACCUCAGAGGCAGCAAG 20 2292

BCLllA-2307 + ACCGAACCUCAGAGGCAGCA 20 2293

BCLllA-2308 + GACCGAACCUCAGAGGCAGC 20 2294

BCLllA-2309 + CUCCCCUCCCGACCGAACCU 20 2295

BCLllA-2310 + CCGCUGCCCUCCCCUCCCGA 20 2296

BCLllA-2311 + GGAGCCCGGACUGCUGCCUC 20 2297

BCLllA-2312 + GGGAGAGGGAGGGAGGGAGC 20 2298

BCLllA-2313 + GCACGCGGGAGAGGGAGGGA 20 2299

BCLllA-2314 + GGCACGCGGGAGAGGGAGGG 20 2300

BCLllA-2315 + GGGCACGCGGGAGAGGGAGG 20 2301

BCLllA-2316 + GGGGGCACGCGGGAGAGGGA 20 2302 BCLllA-2317 + CGGGGGCACGCGGGAGAGGG 20 2303

BCLllA-2318 + CCGGGGGCACGCGGGAGAGG 20 2304

BCLllA-2319 + GGCCGGGGGCACGCGGGAGA 20 2305

BCLllA-2320 + CGGCCGGGGGCACGCGGGAG 20 2306

BCLllA-2321 + GCGGCCGGGGGCACGCGGGA 20 2307

BCLllA-2322 + AGGCGGCCGGGGGCACGCGG 20 2308

BCLllA-2323 + GGAGGCGGCCGGGGGCACGC 20 2309

BCLllA-2324 + AGGAGGCGGCCGGGGGCACG 20 2310

BCLllA-2325 + GAGGAGGCGGCCGGGGGCAC 20 2311

BCLllA-2326 + GGCCGGGGGAGGAGGCGGCC 20 2312

BCLllA-2327 + GGGCCGGGGGAGGAGGCGGC 20 2313

BCLllA-2328 + AGGGCCGGGGGAGGAGGCGG 20 2314

BCLllA-2329 + GCAGGAGCUAGGGCCGGGGG 20 2315

BCLllA-2330 + GGCAGGAGCUAGGGCCGGGG 20 2316

BCLllA-2331 + AGGGCAGGAGCUAGGGCCGG 20 2317

BCLllA-2332 + AAGGGCAGGAGCUAGGGCCG 20 2318

BCLllA-2333 + GAAGGGCAGGAGCUAGGGCC 20 2319

BCLllA-2334 + CGAAGGGCAGGAGCUAGGGC 20 2320

BCLllA-2335 + CCGAAGGGCAGGAGCUAGGG 20 2321

BCLllA-2336 + CGCCGCCGAAGGGCAGGAGC 20 2322

BCLllA-2337 + CGCCGCCGCCGCCGAAGGGC 20 2323

BCLllA-2338 + CCGCCGCCGCCGCCGAAGGG 20 2324

BCLllA-2339 + CGCCGCCGCCGCCGCCGCCG 20 2325

BCLllA-2340 + CGCCGCCGCCGCCGCCGCCG 20 2326

BCLllA-2341 + GCCUUUUGUUCCGGCCAGAG 20 2327

BCLllA-2342 + CUGCCGCCUUU UGUUCCGGC 20 2328

BCLllA-2343 + GCCGUGGGACCGGGAAGGAC 20 2329

BCLllA-2344 + AGCCGUGGGACCGGGAAGGA 20 2330

BCLllA-2345 + GAGCCGUGGGACCGGGAAGG 20 2331

BCLllA-2346 + GGGAGAGCCGUGGGACCGGG 20 2332

BCLllA-2347 + ACGGGGAGAGCCGUGGGACC 20 2333

BCLllA-2348 + GACGGGGAGAGCCGUGGGAC 20 2334

BCLllA-2349 + CGACGGGGAGAGCCGUGGGA 20 2335

BCLllA-2350 + CGCGGCGACGGGGAGAGCCG 20 2336

BCLllA-2351 + CCGCGGCGACGGGGAGAGCC 20 2337

BCLllA-2352 + AGAGGGGCCGCGGCGACGGG 20 2338

BCLllA-2353 + GGAGAGGGGCCGCGGCGACG 20 2339

BCLllA-2354 + GGGAGAGGGGCCGCGGCGAC 20 2340

BCLllA-2355 + CGGGAGAGGGGCCGCGGCGA 20 2341

BCLllA-2356 + UCGGGAGAGGGGCCGCGGCG 20 2342

BCLllA-2357 + UGAGUCCGCGGAGUCGGGAG 20 2343

BCLllA-2358 + CUGAGUCCGCGGAGUCGGGA 20 2344 BCLllA-2359 + UCCUGAGUCCGCGGAGUCGG 20 2345

BCLllA-2360 + GCUCCUGAGUCCGCGGAGUC 20 2346

BCLllA-2361 + CGCUCCUGAGUCCGCGGAGU 20 2347

BCLllA-2362 + GCGCUCCUGAGUCCGCGGAG 20 2348

BCLllA-2363 + CCCCGGCGCUCCUGAGUCCG 20 2349

BCLllA-2364 + CCCCCGGCGCUCCUGAGUCC 20 2350

BCLllA-2365 + GAAAGGGGCCCCCGGCGCUC 20 2351

BCLllA-2366 + GAGAAAGUGGCACUGUGGAA 20 2352

BCLllA-2367 + UGAGAAAGUGGCACUGUGGA 20 2353

BCLllA-2368 + AUAGUGAGAAAGUGGCACUG 20 2354

BCLllA-2369 + AAUAGUGAGAAAGUGGCACU 20 2355

BCLllA-2370 + GUAGUCAUCCCCACAAUAGU 20 2356

BCLllA-2371 + AAGUAGUCAUCCCCACAAUA 20 2357

BCLllA-2372 + ACGGUCAAGUGUGCAGCGGG 20 2358

BCLllA-2373 + CACGGUCAAGUGUGCAGCGG 20 2359

BCLllA-2374 + CUCACGGUCAAGUGUGCAGC 20 2360

BCLllA-2375 + GCUCACGGUCAAGUGUGCAG 20 2361

BCLllA-2376 + CGCUCACGGUCAAGUGUGCA 20 2362

BCLllA-2377 + AAAAGAGGUGAGACUGGCUU 20 2363

BCLllA-2378 + GAUUCCCGGGGAGAAAAGAG 20 2364

BCLllA-2379 + AAAACGAUUCCCGGGGAGAA 20 2365

BCLllA-2380 + U CU AAAAAACG AU U CCCGGG 20 2366

BCLllA-2381 + AGUCUAAAAAACGAUUCCCG 20 2367

BCLllA-2382 + AAGUCU AAAAAACG AUUCCC 20 2368

BCLllA-2383 + CAAGUCUAAAAAACGAUUCC 20 2369

BCLllA-2384 + ACAAGUCU AAAAAACG AUUC 20 2370

BCLllA-2385 + AAUGGGGGGGUAGGGAGGGA 20 2371

BCLllA-2386 + AGAAAAUGGGGGGGUAGGGA 20 2372

BCLllA-2387 + AAGAAAAUGGGGGGGUAGGG 20 2373

BCLllA-2388 + UAAGAAAAUGGGGGGGUAGG 20 2374

BCLllA-2389 + CGUAAGAAAAUGGGGGGGUA 20 2375

BCLllA-2390 + CCGUAAGAAAAUGGGGGGGU 20 2376

BCLllA-2391 + ACCGUAAGAAAAUGGGGGGG 20 2377

BCLllA-2392 + CACUCACCGUAAGAAAAUGG 20 2378

BCLllA-2393 + CCACUCACCGUAAGAAAAUG 20 2379

BCLllA-2394 + CCCACU CACCG UAAGAAAAU 20 2380

BCLllA-2395 + U CCCACU CACCG UAAGAAAA 20 2381

BCLllA-2396 + U U CCCACU CACCG U AAG AAA 20 2382

BCLllA-2397 + GGU UGCUUCCCACUCACCGU 20 2383

BCLllA-2398 + GGUGGGAGCUGGUGGGGAAA 20 2384

BCLllA-2399 + GGGUGGGAGCUGGUGGGGAA 20 2385

BCLllA-2400 + GGGGUGGGAGCUGGUGGGGA 20 2386 BCLllA-2401 + CCUGGGGGUGGGAGCUGGUG 20 2387

BCLllA-2402 + ACCUGGGGGUGGGAGCUGGU 20 2388

BCLllA-2403 + AACCUGGGGGUGGGAGCUGG 20 2389

BCLllA-2404 + AAACCUGGGGGUGGGAGCUG 20 2390

BCLllA-2405 + UCACAUGCAAACCUGGGGGU 20 2391

BCLllA-2406 + CUCACAUGCAAACCUGGGGG 20 2392

BCLllA-2407 + ACUCACAUGCAAACCUGGGG 20 2393

BCLllA-2408 + AACAACUCACAUGCAAACCU 20 2394

BCLllA-2409 + GAACAACUCACAUGCAAACC 20 2395

BCLllA-2410 + CGAACAACUCACAUGCAAAC 20 2396

BCLllA-2411 + UAAUGAACAAUGCUAAGGUU 20 2397

BCLllA-2412 + CCCGCCAGUUUUGCAAAAUA 20 2398

BCLllA-2413 + CUU UAUUUCUCUUU UCGAAA 20 2399

BCLllA-2414 + GCU UUAUUUCUCUU UUCGAA 20 2400

BCLllA-2415 + CCGCCGCUUUAUU UCUCUUU 20 2401

BCLllA-2416 + CCAU UGCCGUGUAUGCACUU 20 2402

BCLllA-2417 + GAAAAAACCCUCAUCCCAUC 20 2403

BCLllA-2418 + GGAAAAAACCCUCAUCCCAU 20 2404

BCLllA-2419 + CG AG G U A A A AG AG A U A A AG G 20 2405

BCLllA-2420 + U CG AGG U AAAAG AG AU AAAG 20 2406

BCLllA-2421 + GUCGAGGUAAAAGAGAUAAA 20 2407

BCLllA-2422 + AGUCGAGGUAAAAGAGAUAA 20 2408

BCLllA-2423 + G AG U CG AGG U AAAAG AG AU A 20 2409

BCLllA-2424 + ACCUCCGAGAGUCGAGGUAA 20 2410

BCLllA-2425 + ACGAGAAAAACCUCCGAGAG 20 2411

BCLllA-2426 + U UUUCACGAGAAAAACCUCC 20 2412

BCLllA-2427 + AU U U U U CACG AG AAAAACCU 20 2413

BCLllA-2428 + UGCAUUUUUAAAUUUU UCAC 20 2414

BCLllA-2429 + CAUGCAUUUUUAAAUUUUUC 20 2415

BCLllA-2430 + AGCAAAAGCGAGGGGGAGAG 20 2416

BCLllA-2431 + AAGCAAAAGCGAGGGGGAGA 20 2417

BCLllA-2432 + AGAAGCAAAAGCGAGGGGGA 20 2418

BCLllA-2433 + CUAGAAGCAAAAGCGAGGGG 20 2419

BCLllA-2434 + GACUAGAAGCAAAAGCGAGG 20 2420

BCLllA-2435 + GGACUAGAAGCAAAAGCGAG 20 2421

BCLllA-2436 + AGGACUAGAAGCAAAAGCGA 20 2422

BCLllA-2437 + CAGGACUAGAAGCAAAAGCG 20 2423

BCLllA-2438 + G C AG G AC U AG AAG CAAA AG C 20 2424

BCLllA-2439 + GCGCAGGACUAGAAGCAAAA 20 2425

BCLllA-2440 + AU CACG AG AG CG CG CAGG AC 20 2426

BCLllA-2441 + U UAAUAAUCACGAGAGCGCG 20 2427

BCLllA-2442 + U AAU AAU U AU U AAU AAU CAC 20 2428 BCLllA-2443 + AAUAAUAAUUAUUAAUAAUC 20 2429

BCLllA-2444 + ACCUCAGAGGCAGCAAG 17 2430

BCLllA-2445 + G AACCU CAG AGG CAG CA 17 2431

BCLllA-2446 + CGAACCUCAGAGGCAGC 17 2432

BCLllA-2447 + CCCUCCCGACCGAACCU 17 2433

BCLllA-2448 + CUGCCCUCCCCUCCCGA 17 2434

BCLllA-2449 + GCCCGGACUGCUGCCUC 17 2435

BCLllA-2450 + AGAGGGAGGGAGGGAGC 17 2436

BCLllA-2451 + CGCGGGAGAGGGAGGGA 17 2437

BCLllA-2452 + ACGCGGGAGAGGGAGGG 17 2438

BCLllA-2453 + CACGCGGGAGAGGGAGG 17 2439

BCLllA-2454 + GGCACGCGGGAGAGGGA 17 2440

BCLllA-2455 + GGGCACGCGGGAGAGGG 17 2441

BCLllA-2456 + GGGGCACGCGGGAGAGG 17 2442

BCLllA-2457 + CGGGGGCACGCGGGAGA 17 2443

BCLllA-2458 + CCGGGGGCACGCGGGAG 17 2444

BCLllA-2459 + GCCGGGGGCACGCGGGA 17 2445

BCLllA-2460 + CGGCCGGGGGCACGCGG 17 2446

BCLllA-2461 + GGCGGCCGGGGGCACGC 17 2447

BCLllA-2462 + AGGCGGCCGGGGGCACG 17 2448

BCLllA-2463 + GAGGCGGCCGGGGGCAC 17 2449

BCLllA-2464 + CGGGGGAGGAGGCGGCC 17 2450

BCLllA-2465 + CCGGGGGAGGAGGCGGC 17 2451

BCLllA-2466 + GCCGGGGGAGGAGGCGG 17 2452

BCLllA-2467 + GGAGCUAGGGCCGGGGG 17 2453

BCLllA-2468 + AGGAGCUAGGGCCGGGG 17 2454

BCLllA-2469 + GCAGGAGCUAGGGCCGG 17 2455

BCLllA-2470 + GGCAGGAGCUAGGGCCG 17 2456

BCLllA-2471 + GGGCAGGAGCUAGGGCC 17 2457

BCLllA-2472 + AGGGCAGGAGCUAGGGC 17 2458

BCLllA-2473 + AAGGGCAGGAGCUAGGG 17 2459

BCLllA-2474 + CGCCGAAGGGCAGGAGC 17 2460

BCLllA-2475 + CGCCGCCGCCGAAGGGC 17 2461

BCLllA-2476 + CCGCCGCCGCCGAAGGG 17 2462

BCLllA-2477 + CGCCGCCGCCGCCGCCG 17 2463

BCLllA-2478 + CGCCGCCGCCGCCGCCG 17 2464

BCLllA-2479 + UUUUGUUCCGGCCAGAG 17 2465

BCLllA-2480 + CCGCCUUU UGUUCCGGC 17 2466

BCLllA-2481 + GUGGGACCGGGAAGGAC 17 2467

BCLllA-2482 + CGUGGGACCGGGAAGGA 17 2468

BCLllA-2483 + CCGUGGGACCGGGAAGG 17 2469

BCLllA-2484 + AGAGCCGUGGGACCGGG 17 2470 BCLllA-2485 + GGGAGAGCCGUGGGACC 17 2471

BCLllA-2486 + GGGGAGAGCCGUGGGAC 17 2472

BCLllA-2487 + CGGGGAGAGCCGUGGGA 17 2473

BCLllA-2488 + GGCGACGGGGAGAGCCG 17 2474

BCLllA-2489 + CGGCGACGGGGAGAGCC 17 2475

BCLllA-2490 + GGGGCCGCGGCGACGGG 17 2476

BCLllA-2491 + GAGGGGCCGCGGCGACG 17 2477

BCLllA-2492 + AGAGGGGCCGCGGCGAC 17 2478

BCLllA-2493 + GAGAGGGGCCGCGGCGA 17 2479

BCLllA-2494 + GGAGAGGGGCCGCGGCG 17 2480

BCLllA-2495 + GUCCGCGGAGUCGGGAG 17 2481

BCLllA-2496 + AGUCCGCGGAGUCGGGA 17 2482

BCLllA-2497 + UGAGUCCGCGGAGUCGG 17 2483

BCLllA-2498 + CCUGAGUCCGCGGAGUC 17 2484

BCLllA-2499 + UCCUGAGUCCGCGGAGU 17 2485

BCLllA-2500 + CUCCUGAGUCCGCGGAG 17 2486

BCLllA-2501 + CGGCGCUCCUGAGUCCG 17 2487

BCLllA-2502 + CCGGCGCUCCUGAGUCC 17 2488

BCLllA-2503 + AGGGGCCCCCGGCGCUC 17 2489

BCLllA-2504 + AAAGUGGCACUGUGGAA 17 2490

BCLllA-2505 + GAAAGUGGCACUGUGGA 17 2491

BCLllA-2506 + GUGAGAAAGUGGCACUG 17 2492

BCLllA-2507 + AG U G AG AAAG U G G C AC U 17 2493

BCLllA-2508 + GUCAUCCCCACAAUAGU 17 2494

BCLllA-2509 + UAGUCAUCCCCACAAUA 17 2495

BCLllA-2510 + GUCAAGUGUGCAGCGGG 17 2496

BCLllA-2511 + GGUCAAGUGUGCAGCGG 17 2497

BCLllA-2512 + ACGGUCAAGUGUGCAGC 17 2498

BCLllA-2513 + C ACG G U CAAG U G U G C AG 17 2499

BCLllA-2514 + UCACGGUCAAGUGUGCA 17 2500

BCLllA-2515 + AGAGGUGAGACUGGCU U 17 2501

BCLllA-2516 + UCCCGGGGAGAAAAGAG 17 2502

BCLllA-2517 + ACGAUUCCCGGGGAGAA 17 2503

BCLllA-2518 + AAAAAACGAUUCCCGGG 17 2504

BCLllA-2519 + CUAAAAAACGAUUCCCG 17 2505

BCLllA-2520 + U CU AAAAAACG AU U CCC 17 2506

BCLllA-2521 + GUCUAAAAAACGAUUCC 17 2507

BCLllA-2522 + AG UCU AAAAAACG AUUC 17 2508

BCLllA-2523 + GGGGGGGUAGGGAGGGA 17 2509

BCLllA-2524 + AAAUGGGGGGGUAGGGA 17 2510

BCLllA-2525 + AAAAUGGGGGGGUAGGG 17 2511

BCLllA-2526 + GAAAAUGGGGGGGUAGG 17 2512 BCLllA-2527 + AAGAAAAUGGGGGGGUA 17 2513

BCLllA-2528 + UAAGAAAAUGGGGGGGU 17 2514

BCLllA-2529 + GUAAGAAAAUGGGGGGG 17 2515

BCLllA-2530 + U C A CCG U A AG A A A A U G G 17 2516

BCLllA-2531 + CUCACCGUAAGAAAAUG 17 2517

BCLllA-2532 + ACUCACCGUAAGAAAAU 17 2518

BCLllA-2533 + CACU CACCG UAAGAAAA 17 2519

BCLllA-2534 + CCACUCACCGUAAGAAA 17 2520

BCLllA-2535 + UGCUUCCCACUCACCGU 17 2521

BCLllA-2536 + GGGAGCUGGUGGGGAAA 17 2522

BCLllA-2537 + UGGGAGCUGGUGGGGAA 17 2523

BCLllA-2538 + GUGGGAGCUGGUGGGGA 17 2524

BCLllA-2539 + GGGGGUGGGAGCUGGUG 17 2525

BCLllA-2540 + UGGGGGUGGGAGCUGGU 17 2526

BCLllA-2541 + CUGGGGGUGGGAGCUGG 17 2527

BCLllA-2542 + CCUGGGGGUGGGAGCUG 17 2528

BCLllA-2543 + CAUGCAAACCUGGGGGU 17 2529

BCLllA-2544 + ACAUGCAAACCUGGGGG 17 2530

BCLllA-2545 + CACAUGCAAACCUGGGG 17 2531

BCLllA-2546 + AAC U CAC AU G CAAACCU 17 2532

BCLllA-2547 + CAACUCACAUGCAAACC 17 2533

BCLllA-2548 + ACAACUCACAUGCAAAC 17 2534

BCLllA-2549 + UGAACAAUGCUAAGGUU 17 2535

BCLllA-2550 + GCCAGUUUUGCAAAAUA 17 2536

BCLllA-2551 + UAUUUCUCUUUUCGAAA 17 2537

BCLllA-2552 + UUAUUUCUCUUUUCGAA 17 2538

BCLllA-2553 + CCGCUUUAUUUCUCUU U 17 2539

BCLllA-2554 + UUGCCGUGUAUGCACUU 17 2540

BCLllA-2555 + AAAACCCUCAUCCCAUC 17 2541

BCLllA-2556 + AAAAACCCUCAUCCCAU 17 2542

BCLllA-2557 + G G U A A A AG AG A U A A AG G 17 2543

BCLllA-2558 + AG G U A A A AG AG A U A A AG 17 2544

BCLllA-2559 + G AGG U AAAAG AG AU AAA 17 2545

BCLllA-2560 + CG AG G U A A A AG AG A U A A 17 2546

BCLllA-2561 + U CG AGG U AAAAG AG AU A 17 2547

BCLllA-2562 + UCCGAGAGUCGAGGUAA 17 2548

BCLllA-2563 + AGAAAAACCUCCGAGAG 17 2549

BCLllA-2564 + UCACGAGAAAAACCUCC 17 2550

BCLllA-2565 + U U U CACG AG AAAAACCU 17 2551

BCLllA-2566 + AUUUUUAAAUUUUUCAC 17 2552

BCLllA-2567 + GCAUUUUUAAAUUUUUC 17 2553

BCLllA-2568 + AAAAGCGAGGGGGAGAG 17 2554 BCLllA-2569 + CAAAAGCGAGGGGGAGA 17 2555

BCLllA-2570 + AGCAAAAGCGAGGGGGA 17 2556

BCLllA-2571 + G A AG C A A A AG CG AG G G G 17 2557

BCLllA-2572 + U AG AAG CAAAAG CG AGG 17 2558

BCLllA-2573 + CUAGAAGCAAAAGCGAG 17 2559

BCLllA-2574 + ACU AG AAG CAAAAG CG A 17 2560

BCLllA-2575 + G ACU AG AAG CAAAAG CG 17 2561

BCLllA-2576 + GGACUAGAAG CAAAAG C 17 2562

BCLllA-2577 + CAGGACUAGAAG C A A A A 17 2563

BCLllA-2578 + ACGAGAGCGCGCAGGAC 17 2564

BCLllA-2579 + AUAAUCACGAGAGCGCG 17 2565

BCLllA-2580 + U AAU U AU U AAU AAU CAC 17 2566

BCLllA-2581 + AAUAAUUAUUAAUAAUC 17 2567

Table 2C provides exemplary targeting domains for repressing (i.e., knocking down or decreasing) expression of the BCLllA gene by targeting within the lOOObp of sequence 3' of 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 N. meningitidis eiCas9 molecule to cause a steric block at the target region, e.g., within lOOObp of sequence 3' of the start codon to block transcription resulting in the repression of the BCLllA gene. Alternatively, any of the targeting domains in the table can be used with a N. meningitidis eiCas9 fused to a transcriptional repressor to decrease transcription and therefore downregulate gene expression.

Table 2C

Table 3A provides exemplary targeting domains for knocking out the BCLllA gene by targeting the early coding sequence the BCLllA gene selected according to first tier parameters. The targeting domains are within first 500bp of coding sequence downstream of start codon, good orthogonality, start with G. 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 generates a double strand break (Cas9 nuclease) or a single-strand break (Cas9 nickase). In an embodiment, dual targeting is used to create two double strand breaks to remove the enhancer region in the BCLllA gene, e.g., the first gRNA is used to target upstream (i.e., 5') of the enhancer region in the BCLllA gene and the second gRNA is used to target downstream (i.e., 3') of the enhancer region in the BCLllA gene.

Any of the targeting domains in the table can be used with a S. pyogenes Cas9 (nickase) molecule to generate a single strand break. 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. Exemplary gRNA pairs are: BCL11A- 2607 and BCL11A-2593, BCL11A-2607 and BCL11A-2598, BCL11A-264 and BCL11A-2593, BCL11A-2614 and BCL11A-2598, BCL11A-2589 and BCL11A-2664, BCL11A-2589 and BCLl lA-2666, BCLl lA-2596 and BCLl lA-2664, BCLl lA-2596 and BCLl lA-2666,

BCLl lA-2603 and BCLl lA-2664, of BCLl lA-2603 and BCLl lA-2666.

In an embodiment, four gRNAs (e.g., two pairs) are used to target four Cas9 nickases to create four nicks to remove the enhancer region in the BCLllA gene, e.g., the first pair of gRNAs are used to target upstream (i.e., 5') of the enhancer region in the BCLllA gene and the second pair of gRNAs are used to target downstream (i.e., 3') of the enhancer region in the BCLllA gene. For example, gRNA pairs that target upstream (i.e., 5') of the enhancer region in the BCLllA gene (e.g., 2607 and BCLl lA-2593, BCLl lA-2607 and BCLl lA-2598, BCL11A- 264 and BCL11A-2593, or BCL11A-2614 and BCL11A-2598) can be paired with gRNA pairs that target downstream (i.e., 3') of the enhancer region in the BCLllA gene (e.g., BCL11A-2589 and BCL11A-2664, BCL11A-2589 and BCL11 A-2666, BCL11A-2596 and BCL11A-2664, BCL11 A-2596 and BCL11 A-2666, BCL11 A-2603 and BCL11 A-2664, or BCL11 A-2603 and BCLl lA-2666).

Table 3A 1st Tier

DNA Target Site SEQ ID gRNA Name Targeting Domain

Strand Length NO

BCLllA-2588 + GAGCTCCATGTGCAGAACGA 20 2574

BCLllA-2589 + GAGCTCCCAACGGGCCG 17 2575

BCLllA-2590 - GAGTGCAGAATATGCCCCGC 20 2576

BCLllA-2591 + GATAAACAATCGTCATCCTC 20 2577

BCLllA-2592 + GATGCCAACCTCCACGGGAT 20 2578

BCLllA-2593 - GCAGAATATGCCCCGCA 17 2579

BCLllA-2594 - GCATCCAATCCCGTGGAGGT 20 2580

BCLllA-2595 + GCCAACCTCCACGGGAT 17 2581

BCLllA-2596 + GCTCCCAACGGGCCGTGGTC 20 2582

BCLllA-2597 - GGAGCTCTAATCCCCACGCC 20 2583

Table 3B provides exemplary targeting domains for knocking out the BCL11A gene by targeting the early coding sequence the BCL11A gene selected according to second tier parameters. The targeting domains are within first 500bp of coding sequence downstream of start codon, good orthogonality, and do not start with G. 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 generates a double strand break (Cas9 nuclease) or a single-strand break (Cas9 nickase). In an embodiment, dual targeting is used to create two double strand breaks to remove the enhancer region in the BCL11A gene, e.g., the first gRNA is used to target upstream (i.e., 5') of the enhancer region in the BCL11A gene and the second gRNA is used to target downstream (i.e., 3') of the enhancer region in the BCL11A gene.

In an embodiment, four gRNAs (e.g., two pairs) are used to target four Cas9 nickases to create four nicks to remove the enhancer region in the BCL11A gene, e.g., the first pair of gRNAs are used to target upstream (i.e., 5') of the enhancer region in the BCLllA gene and the second pair of gRNAs are used to target downstream (i.e., 3') of the enhancer region in the BCLllA gene.

Table 3B

Table 3C provides exemplary targeting domains for knocking out the BCLllA gene by targeting the early coding sequence the BCLllA gene selected according to third tier parameters. The targeting domains are within first 500bp of coding sequence downstream of start codon and start with G. 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 generates a double strand break (Cas9 nuclease) or a single- strand break (Cas9 nickase). In an embodiment, dual targeting is used to create two double strand breaks to remove the enhancer region in the BCLllA gene, e.g., the first gRNA is used to target upstream (i.e., 5') of the enhancer region in the BCLllA gene and the second gRNA is used to target downstream (i.e., 3') of the enhancer region in the BCLllA gene.

In an embodiment, four gRNAs (e.g., two pairs) are used to target four Cas9 nickases to create four nicks to remove the enhancer region in the BCL11A gene, e.g., the first pair of gRNAs are used to target upstream (i.e., 5') of the enhancer region in the BCL11A gene and the second pair of gRNAs are used to target downstream (i.e., 3') of the enhancer region in the BCL11A gene.

Table 3C

BCLllA-2639 + GTTC ATCTG G C ACTG CCC AC 20 2625

BCLllA-2640 - GTTGGGAGCTCCAGAAG 17 2626

Table 3D provides exemplary targeting domains for knocking out the BCLllA gene by targeting the early coding sequence the BCLllA gene selected according to forth tier parameters. The targeting domains are within first 500bp of coding sequence downstream of start codon and do not start with G. 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 generates a double strand break (Cas9 nuclease) or a single-strand break (Cas9 nickase). In an embodiment, dual targeting is used to create two double strand breaks to remove the enhancer region in the BCLllA gene, e.g., the first gRNA is used to target upstream (i.e., 5') of the enhancer region in the BCLllA gene and the second gRNA is used to target downstream (i.e., 3') of the enhancer region in the BCLllA gene.

In an embodiment, four gRNAs (e.g., two pairs) are used to target four Cas9 nickases to create four nicks to remove the enhancer region in the BCLllA gene, e.g., the first pair of gRNAs are used to target upstream (i.e., 5') of the enhancer region in the BCLllA gene and the second pair of gRNAs are used to target downstream (i.e., 3') of the enhancer region in the BCLllA gene.

Table 3D

BCLllA-2646 - AAACTTCTGCACTGGAG 17 2632

BCLllA-2647 + AAATAAGAATGTCCCCCAAT 20 2633

BCLllA-2648 - AACCCCAGCACTTAAGCAAA 20 2634

BCLllA-2649 + AAGAATGGCTTCAAGAGGCT 20 2635

BCLllA-2650 + A ATG G CTTC A AG AG G CT 17 2636

BCLllA-2651 - ACAGATGATGAACCAGACCA 20 2637

BCLllA-2652 - ACCAGACCACGGCCCGT 17 2638

BCLllA-2653 - ACCCC AG CACTTAAG CAAAC 20 2639

BCLllA-2654 + ACCTGGATGCCAACCTCCAC 20 2640

BCLllA-2655 + ACTGCCCACAGGTGAGG 17 2641

BCLllA-2656 + AGAGCTCCATGTGCAGAACG 20 2642

BCLllA-2657 - AGATGAACTTCCCATTG 17 2643

BCLllA-2658 + AGCTCCATGTGCAGAACGAG 20 2644

BCLllA-2659 - AGGAATTTGCCCCAAAC 17 2645

BCLllA-2660 + AGGAGGTCATGATCCCCTTC 20 2646

BCLllA-2661 + AGGTCATGATCCCCTTC 17 2647

BCLllA-2662 - ATAAACTTCTGCACTGG 17 2648

BCLllA-2663 + ATAAGAATGTCCCCCAA 17 2649

BCLllA-2664 - ATCATGACCTCCTCACCTGT 20 2650

BCLllA-2665 + ATCTCGATTGGTGAAGGGGA 20 2651

BCLllA-2666 - ATGACCTCCTCACCTGT 17 2652

BCLllA-2667 + ATGTGCAGAACGAGGGG 17 2653

BCLllA-2668 + ATTGGTGAAGGGGAAGG 17 2654

BCLllA-2669 - CACAAACGGAAACAATGCAA 20 2655

BCLllA-2670 + CACTCATCCCAGGCGTG 17 2656

BCLllA-2671 + CAGAACGAGGGGAGGAG 17 2657

BCLllA-2672 - CAGATGAACTTCCCATT 17 2658

BCLllA-2673 + C AG CTTTTTCTAAG CAG 17 2659

BCLllA-2674 - CATCCAGGTCACGCCAG 17 2660

BCLllA-2675 + CATCTCGATTGGTGAAG 17 2661

BCLllA-2676 + CATCTGGCACTGCCCAC 17 2662

BCLllA-2677 - CATGACCTCCTCACCTG 17 2663

BCLllA-2678 + C C A ATG G G A AGTTC ATC 17 2664

BCLllA-2679 + CCACAGCTTTTTCTAAGCAG 20 2665

BCLllA-2680 - CCAGACCACGGCCCGTT 17 2666

BCLllA-2681 - CCAGATGAACTTCCCAT 17 2667

BCLllA-2682 - CCAGATGAACTTCCCATTGG 20 2668

BCLllA-2683 - CCAG CACTTAAG CAAAC 17 2669

BCLllA-2684 - CCCAGCACTTAAGCAAA 17 2670

BCLllA-2685 + CCCCTTCTGGAGCTCCCAAC 20 2671

BCLllA-2686 - CCCGTTGGGAGCTCCAGAAG 20 2672

BCLllA-2687 - CCGTTGGGAGCTCCAGA 17 2673 BCLllA-2688 + CCGTTTG CTTAAGTG CT 17 2674

BCLllA-2689 - CCTCTGCTTAGAAAAAGCTG 20 2675

BCLllA-2690 + CCTTCTGGAGCTCCCAA 17 2676

BCLllA-2691 - CGTGGAGGTTGGCATCC 17 2677

BCLllA-2692 - CGTTG G G AG CTC C AG A A 17 2678

BCLllA-2693 + CGTTTG CTTAAGTG CTG 17 2679

BCLllA-2694 + CTATGTGTTCCTGTTTG 17 2680

BCLllA-2695 + CTCCATGTGCAGAACGA 17 2681

BCLllA-2696 - CTCTAATCCCCACGCCT 17 2682

BCLllA-2697 + CTG CACTCATCCCAGG CGTG 20 2683

BCLllA-2698 + CTG CTATGTGTTCCTGTTTG 20 2684

BCLllA-2699 - CTG CTTAG AAAAAG CTG 17 2685

BCLllA-2700 + CTGGAGCTCCCAACGGGCCG 20 2686

BCLllA-2701 + CTGGATGCCAACCTCCA 17 2687

BCLllA-2702 + CTTCTGGAGCTCCCAAC 17 2688

BCLllA-2703 - TAAACTTCTGCACTGGA 17 2689

BCLllA-2704 + TAAGAATGTCCCCCAAT 17 2690

BCLllA-2705 - TAGAGGAATTTGCCCCAAAC 20 2691

BCLllA-2706 + TATTCTGCACTCATCCC 17 2692

BCLllA-2707 + TCCATGTGCAGAACGAG 17 2693

BCLllA-2708 + TCCATGTGCAGAACGAGGGG 20 2694

BCLllA-2709 - TCCCCTCGTTCTGCACA 17 2695

BCLllA-2710 + TCCCCTTCTGGAGCTCCCAA 20 2696

BCLllA-2711 - TCCCGTGGAGGTTGGCATCC 20 2697

BCLllA-2712 - TCCTCCCCTCGTTCTGCACA 20 2698

BCLllA-2713 + TCGATTGGTGAAGGGGA 17 2699

BCLllA-2714 + TCG ATTG GTG AAG GG G AAG G 20 2700

BCLllA-2715 + TCTG CACTCATCCCAGG CGT 20 2701

BCLllA-2716 + TCTGGCACTGCCCACAGGTG 20 2702

BCLllA-2717 + TCTGTAAGAATGGCTTCAAG 20 2703

BCLllA-2718 + TG CACTCATCCCAGG CG 17 2704

BCLllA-2719 - TGCCAGATGAACTTCCCATT 20 2705

BCLllA-2720 + TG CTATGTGTTCCTGTT 17 2706

BCLllA-2721 + TGGATGCCAACCTCCAC 17 2707

BCLllA-2722 + TG GTTC ATC ATCTGTAAG AA 20 2708

BCLllA-2723 - TGTTTATCAACGTCATCTAG 20 2709

BCLllA-2724 - 1 I A I 1 1 1 1 A I A A AAA 20 2710

BCLllA-2725 + TTCATCATCTGTAAGAA 17 2711

BCLllA-2726 + TTCCCGTTTGCTTAAGTGCT 20 2712

BCLllA-2727 + TTCTGCACTCATCCCAGGCG 20 2713

BCLllA-2728 + TTTCATCTCG ATTG GTG AAG 20 2714

BCLllA-2729 + TTTTC ATCTCG ATTG GTG AA 20 2715 BCLllA-2730 - 1 1 1 1 1 ATCGAGCACAAA 17 2716

BCLllA-2731 + TTTTTCATCTCGATTGGTGA 20 2717

Table 3E provides exemplary targeting domains for knocking out the BCLllA gene by targeting the early coding sequence the BCLllA gene selected according to fifth tier parameters. The targeting domains outside the first 500bp of coding sequence downstream of 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 generates a double strand break (Cas9 nuclease) or a single-strand break (Cas9 nickase). In an embodiment, dual targeting is used to create two double strand breaks to remove the enhancer region in the BCLllA gene, e.g., the first gRNA is used to target upstream (i.e., 5') of the enhancer region in the BCLllA gene and the second gRNA is used to target downstream (i.e., 3') of the enhancer region in the BCLllA gene.

Table 3E

BCLllA-2737 + CTGGGTACTACGCCGAA 17 2723

BCLllA-2738 + GGGTACTACGCCGAATG 17 2724

BCLllA-2739 + TCGGACTTGACCGTCAT 17 2725

BCLllA-2740 + AGGGATACCAACCCGCG 17 2726

BCLllA-2741 - CGCGCTCAAGTCCGTGG 17 2727

BCLllA-2742 + CGAGGAGTGCTCCGACG 17 2728

BCLllA-2743 + GTCGGACTTGACCGTCA 17 2729

BCLllA-2744 + TGCACGCGTGGTCGCAC 17 2730

BCLllA-2745 - CAG CG CG CTCAAGTCCG 17 2731

BCLllA-2746 + TACCAACCCGCGGGGTC 17 2732

BCLllA-2747 - GTG G CTCG CCG G CTACG 17 2733

BCLllA-2748 + CGGACTTGACCGTCATG 17 2734

BCLllA-2749 - C ACCG C ATAG AG CG CCT 17 2735

BCLllA-2750 - GCGCATCAAGCTCGAGA 17 2736

BCLllA-2751 + GGCCCGGACCACTAATA 17 2737

BCLllA-2752 + GCCCGGACCACTAATAT 17 2738

BCLllA-2753 - GCATAAGCGCGGCCACC 17 2739

BCLllA-2754 + AGGCGCTCTATGCGGTG 17 2740

BCLllA-2755 - ACGGTCAAGTCCGACGA 17 2741

BCLllA-2756 + CGAGGCCGACTCGCCCG 17 2742

BCLllA-2757 - ACCG C ATAG AG CG CCTG 17 2743

BCLllA-2758 - CGACCACGCGTGCACCC 17 2744

BCLllA-2759 + GTACACGTTCTCCGTGT 17 2745

BCLllA-2760 - CACTTGCGACGAAGACT 17 2746

BCLllA-2761 - CGGGTTGGTATCCCTTC 17 2747

BCLllA-2762 - CTCGTCGGAGCACTCCT 17 2748

BCLllA-2763 + CCCGGACCACTAATATG 17 2749

BCLllA-2764 + TCGGTGGTGGACTAAAC 17 2750

BCLllA-2765 + CAG G CG CTCTATG CGGT 17 2751

BCLllA-2766 + AAGGGATACCAACCCGC 17 2752

BCLllA-2767 + GGCGCTCTATGCGGTGG 17 2753

BCLllA-2768 - CCACCGCATAGAGCGCC 17 2754

BCLllA-2769 - TACTCG CAGTG G CTCG C 17 2755

BCLllA-2770 - CGGGCGAGTCGGCCTCG 17 2756

BCLllA-2771 + TACACGTTCTCCGTGTT 17 2757

BCLllA-2772 - AGCACGCCCCATATTAG 17 2758

BCLllA-2773 + GAAGGGATACCAACCCG 17 2759

BCLllA-2774 + TTGGGCATCGCGGCCGG 17 2760

BCLllA-2775 - CCGGGCGAGTCGGCCTC 17 2761

BCLllA-2776 + GGTGGAGAGACCGTCGT 17 2762

BCLllA-2777 + GTTGGGCATCGCGGCCG 17 2763

BCLllA-2778 - AGAACGTGTACTCGCAG 17 2764 BCLllA-2779 + ACCAACCCGCGGGGTCA 17 2765

BCLllA-2780 - CACGAGAACAGCTCGCG 17 2766

BCLllA-2781 - TATTAGTGGTCCGGGCC 17 2767

BCLllA-2782 + CGTCG CAAGTGTCCCTG 17 2768

BCLllA-2783 + CCCGCGAGCTGTTCTCG 17 2769

BCLllA-2784 + TGCGCCGGTGCACCACC 17 2770

BCLllA-2785 - CTGCCCGACGTCATGCA 17 2771

BCLllA-2786 - GACGAAGACTCGGTGGC 17 2772

BCLllA-2787 - CCTGCCCGACGTCATGC 17 2773

BCLllA-2788 + AAG GG CG G CTTG CTACC 17 2774

BCLllA-2789 - GGGTGGACTACGGCTTC 17 2775

BCLllA-2790 + TCGCTGGTGCCGGGTTC 17 2776

BCLllA-2791 - GGCGAGAAGCATAAGCG 17 2777

BCLllA-2792 + G G ACTTG AG CG CG CTG C 17 2778

BCLllA-2793 - CTCGGTGGCCGGCGAGT 17 2779

BCLllA-2794 + CCCGAGGCCGACTCGCC 17 2780

BCLllA-2795 - CCCGGGCGAGTCGGCCT 17 2781

BCLllA-2796 - C CG CAT AG AG CG C CTG G 17 2782

BCLllA-2797 + TGTTGGGCATCGCGGCC 17 2783

BCLllA-2798 + GTGTTGGGCATCGCGGC 17 2784

BCLllA-2799 + TCTCTCGATACTGATCC 17 2785

BCLllA-2800 - ACCCGAGTGCCTTTGAC 17 2786

BCLllA-2801 + TCCGACGAGGAGGCAAA 17 2787

BCLllA-2802 - ACCCGGCACCAGCGACT 17 2788

BCLllA-2803 + CCCCGTTCTCCGGGATC 17 2789

BCLllA-2804 + CCGAGGCCGACTCGCCC 17 2790

BCLllA-2805 - CCCCATATTAGTGGTCC 17 2791

BCLllA-2806 + GACTTGGACTTGACCGG 17 2792

BCLllA-2807 - GCCCCATATTAGTGGTC 17 2793

BCLllA-2808 - AGGGTGGACTACGGCTT 17 2794

BCLllA-2809 - CAAATCGTCCCCCATGA 17 2795

BCLllA-2810 - CGACGTCATGCAGGGCA 17 2796

BCLllA-2811 - GGCCGCGATGCCCAACA 17 2797

BCLllA-2812 + CC AGG CG CTCTATG CG G 17 2798

BCLllA-2813 - CCTGATCCCGGAGAACG 17 2799

BCLllA-2814 + CCAACCCGCGGGGTCAG 17 2800

BCLllA-2815 - GGCGAGTCGGCCTCGGG 17 2801

BCLllA-2816 + G G CAAAAG G CG ATTGTC 17 2802

BCLllA-2817 + TTTGGACAGGCCCCCCG 17 2803

BCLllA-2818 + G CG G CTTG CTAC CTG G C 17 2804

BCLllA-2819 + GGACTTGACCGTCATGG 17 2805

BCLllA-2820 + GGAGTGCTCCGACGAGG 17 2806 BCLllA-2821 - ATTAGTGGTCCGGGCCC 17 2807

BCLllA-2822 - CCACG AG AACAG CTCG C 17 2808

BCLllA-2823 - GTATCGAGAGAGGCTTC 17 2809

BCLllA-2824 + CTCCGTGTTGGGCATCG 17 2810

BCLllA-2825 + CAAACTCCCGTTCTCCG 17 2811

BCLllA-2826 - ACCTGATCCCGGAGAAC 17 2812

BCLllA-2827 - GGCACTGTTAATGGCCG 17 2813

BCLllA-2828 + TTCTCCGGGATCAGGTT 17 2814

BCLllA-2829 - TATGGAGCCTCCCGCCA 17 2815

BCLllA-2830 + CTTGATGCGCTTAGAGA 17 2816

BCLllA-2831 - TAG C A AG C CG C C CTTC C 17 2817

BCLllA-2832 - CCGGCTACGCGGCCTCC 17 2818

BCLllA-2833 + TCC AAGTG ATGTCTCG G 17 2819

BCLllA-2834 - GAACAGCTCGCGGGGCG 17 2820

BCLllA-2835 - GCTGCGGTTGAATCCAA 17 2821

BCLllA-2836 + TGACTTGGACTTGACCG 17 2822

BCLllA-2837 - CCCGGAGAACGGGGACG 17 2823

BCLllA-2838 + GTGGCGCTTCAGCTTGC 17 2824

BCLllA-2839 + GTTCTCCGGGATCAGGT 17 2825

BCLllA-2840 + CAGTG CC ATCGTCTATG 17 2826

BCLllA-2841 + TCTCCGGGATCAGGTTG 17 2827

BCLllA-2842 - GACGATGGCACTGTTAA 17 2828

BCLllA-2843 - CTGCTCCCCGGGCGAGT 17 2829

BCLllA-2844 + CGGTGGTGGACTAAACA 17 2830

BCLllA-2845 - CTCGCGGGGCGCGGTCG 17 2831

BCLllA-2846 + ATGCCCTGCATGACGTC 17 2832

BCLllA-2847 + TGGACTTGACCGGGGGC 17 2833

BCLllA-2848 - ACCACCGAGACATCACT 17 2834

BCLllA-2849 - GGAGTTCGACCTGCCCC 17 2835

BCLllA-2850 + CCTG CATG ACGTCG GG C 17 2836

BCLllA-2851 + CTGCATGACGTCGGGCA 17 2837

BCLllA-2852 - AGGATCAGTATCGAGAG 17 2838

BCLllA-2853 + GGACTTGACCGGGGGCT 17 2839

BCLllA-2854 + AAAGGCACTCGGGTGAT 17 2840

BCLllA-2855 - TGGACGGAGGGATCTCG 17 2841

BCLllA-2856 + CCCCCAGGCGCTCTATG 17 2842

BCLllA-2857 - CCGCCATGGATTTCTCT 17 2843

BCLllA-2858 - GGCGCGGTCGTGGGCGT 17 2844

BCLllA-2859 - AACCTGATCCCGGAGAA 17 2845

BCLllA-2860 + CATGCCCTGCATGACGT 17 2846

BCLllA-2861 + CGCTGGTGCCGGGTTCC 17 2847

BCLllA-2862 + CCTGGAGGCCGCGTAGC 17 2848 BCLllA-2863 - CCCCTGACCCCGCGGGT 17 2849

BCLllA-2864 + G CTTATG CTTCTCG CCC 17 2850

BCLllA-2865 - AAGTCATG CG AGTTCTG 17 2851

BCLllA-2866 + CACCAAGTCG CTGGTG C 17 2852

BCLllA-2867 - CCCGAGTGCCTTTGACA 17 2853

BCLllA-2868 + CATGACTTGGACTTGAC 17 2854

BCLllA-2869 - CGACCCCAACCTGATCC 17 2855

BCLllA-2870 + ACCAAGTCGCTGGTGCC 17 2856

BCLllA-2871 + AAGTGATGTCTCGGTGG 17 2857

BCLllA-2872 - CTTCTCCACACCGCCCG 17 2858

BCLllA-2873 + TGGAGTCTCCGAAGCTA 17 2859

BCLllA-2874 - CGCTTCTCCACACCGCC 17 2860

BCLllA-2875 + GCTGGTGCCGGGTTCCG 17 2861

BCLllA-2876 - CGCAGCGGCACGGGAAG 17 2862

BCLllA-2877 + GCATCGCGGCCGGGGGC 17 2863

BCLllA-2878 - GAGCACTCCTCGGAGAA 17 2864

BCLllA-2879 + GGGGGGCGTCGCCAGGA 17 2865

BCLllA-2880 + G A AAG CG CCCTTCTG CC 17 2866

BCLllA-2881 - CTGGACGGAGGGATCTC 17 2867

BCLllA-2882 - CGGCTTCGGGCTGAGCC 17 2868

BCLllA-2883 + GGGGGCGTCGCCAGGAA 17 2869

BCLllA-2884 + TA A CCTTTG C ATAG G G C 17 2870

BCLllA-2885 - GGGCGAGTCGGCCTCGG 17 2871

BCLllA-2886 - CACACCGCCCGGGGAGC 17 2872

BCLllA-2887 - GGGATCTCGGGGCGCAG 17 2873

BCLllA-2888 + CTCG CTG A AGTG CTG C A 17 2874

BCLllA-2889 - TCGGGGCGCAGCGGCAC 17 2875

BCLllA-2890 - AAGTCCCCTGACCCCGC 17 2876

BCLllA-2891 - GCCTTTTGCCTCCTCGT 17 2877

BCLllA-2892 - CACCTGGCCGAGGCCGA 17 2878

BCLllA-2893 - GGTATCCCTTCAGGACT 17 2879

BCLllA-2894 + GTGGTG G ACTAA ACAG G 17 2880

BCLllA-2895 + GCGAGCTGTTCTCGTGG 17 2881

BCLllA-2896 - AGCACTCCTCGGAGAAC 17 2882

BCLllA-2897 - CATG CAG CACTTCAG CG 17 2883

BCLllA-2898 + TGGCCTGGGTGCACGCG 17 2884

BCLllA-2899 - AGCGAGAGGGTGGACTA 17 2885

BCLllA-2900 + G CACAG GTTG CACTTGT 17 2886

BCLllA-2901 + GAGAAATCCATGGCGGG 17 2887

BCLllA-2902 + GCAGAACTCGCATGACT 17 2888

BCLllA-2903 + TCTCCGAAGCTAAGGAA 17 2889

BCLllA-2904 + TGACGTCGGGCAGGGCG 17 2890 BCLllA-2905 + GGGTCCAAGTGATGTCT 17 2891

BCLllA-2906 - GCAACCTGGTGGTGCAC 17 2892

BCLllA-2907 + GGTGGCGCGCCGCCTCC 17 2893

BCLllA-2908 + GCTGCCCACCAAGTCGC 17 2894

BCLllA-2909 + GTTCTCG CTCTTG AACT 17 2895

BCLllA-2910 + CCGCAGCACCCTGTCAA 17 2896

BCLllA-2911 - GAAGTCCCCTGACCCCG 17 2897

BCLllA-2912 - GCGCGGCCACCTGGCCG 17 2898

BCLllA-2913 + GGCGTCGCCAGGAAGGG 17 2899

BCLllA-2914 - GTTG A ATC C A ATG G CT A 17 2900

BCLllA-2915 - CTCGGGGCGCAGCGGCA 17 2901

BCLllA-2916 - CCGAGGCCGAGGGCCAC 17 2902

BCLllA-2917 + CTAAACAGGGGGGGAGT 17 2903

BCLllA-2918 - GCGGCACGGGAAGTGGA 17 2904

BCLllA-2919 + CACAGGTTGCACTTGTA 17 2905

BCLllA-2920 - CAGCGAGGCCTTCCACC 17 2906

BCLllA-2921 - AACCTGCTAAGAATACC 17 2907

BCLllA-2922 + ATC CTG GTATTCTT AG C 17 2908

BCLllA-2923 + GGTGGTGGACTAAACAG 17 2909

BCLllA-2924 - CGAGGCCGAGGGCCACA 17 2910

BCLllA-2925 + GTACATGTGTAG CTG CT 17 2911

BCLllA-2926 + TTG ATG CG CTTAG AG AA 17 2912

BCLllA-2927 + TCCTCGTCCCCGTTCTC 17 2913

BCLllA-2928 + ATGACTTGGACTTGACC 17 2914

BCLllA-2929 + GTCTCCGAAGCTAAGGA 17 2915

BCLllA-2930 + GGTGGACTAAACAGGGG 17 2916

BCLllA-2931 + GCATGTGCGTCTTCATG 17 2917

BCLllA-2932 + GGCACTCGGGTGATGGG 17 2918

BCLllA-2933 + ATAGGGCTGGGCCGGCC 17 2919

BCLllA-2934 + CCGTCCAGCTCCCCGGG 17 2920

BCLllA-2935 + GCAGTAACCTTTGCATA 17 2921

BCLllA-2936 - GATCCCTTCCTTAGCTT 17 2922

BCLllA-2937 + AAG GG G CTC AG CG AG CT 17 2923

BCLllA-2938 - AGCTGACGGAGAGCGAG 17 2924

BCLllA-2939 - TCGCGGGGCGCGGTCGT 17 2925

BCLllA-2940 - AGCGGCACGGGAAGTGG 17 2926

BCLllA-2941 + CAAAGGCACTCGGGTGA 17 2927

BCLllA-2942 + CTGCACCTAGTCCTGAA 17 2928

BCLllA-2943 - GCTGGACGGAGGGATCT 17 2929

BCLllA-2944 + CCCTGTCAAAG G C ACTC 17 2930

BCLllA-2945 + A A C CTTTG CATAGGGCT 17 2931

BCLllA-2946 + CGCCCGGGGAGCAGCCG 17 2932 BCLllA-2947 + TGGTGGACTAAACAGGG 17 2933

BCLllA-2948 - GGCCCAGCC CT ATG C A A 17 2934

BCLllA-2949 + CCTCGTCCCCGTTCTCC 17 2935

BCLllA-2950 - GCCAGCTCCCCGGAACC 17 2936

BCLllA-2951 + GCCGGGTTCCGGGGAGC 17 2937

BCLllA-2952 + TG C AGTAACCTTTG CAT 17 2938

BCLllA-2953 + GCTTCTCGCCCAGGACC 17 2939

BCLllA-2954 - CCGCCCGGGGAGCTGGA 17 2940

BCLllA-2955 - CCGGGGAGCTGGACGGA 17 2941

BCLllA-2956 - CTTCCGGCCTGGCAGAA 17 2942

BCLllA-2957 + CCTAGAGAAATCCATGG 17 2943

BCLllA-2958 + GGAGGGGGGGCGTCGCC 17 2944

BCLllA-2959 - TACTTAGAAAGCGAACA 17 2945

BCLllA-2960 + GGAGGCTCCATAGCCAT 17 2946

BCLllA-2961 + ACACATCTTGAGCTCTC 17 2947

BCLllA-2962 - GGCACCAGCGACTTGGT 17 2948

BCLllA-2963 + GGGATCTTTGAGCTGCC 17 2949

BCLllA-2964 + GCAGCAG I 1 1 1 1 GAC 17 2950

BCLllA-2965 + CTG C A AT ATG A ATC CC A 17 2951

BCLllA-2966 + TCTGCACCTAGTCCTGA 17 2952

BCLllA-2967 + GAAGGGGCTCAGCGAGC 17 2953

BCLllA-2968 + TTCCGGGGAGCTGGCGG 17 2954

BCLllA-2969 - GCACCGGCGCAGCCACA 17 2955

BCLllA-2970 + ATATGAATCCCATGGAG 17 2956

BCLllA-2971 - GTGGTCCGGGCCCGGGC 17 2957

BCLllA-2972 - CTTCACACACCCCCATT 17 2958

BCLllA-2973 - GTCCAAA AAG CTG CTG C 17 2959

BCLllA-2974 - CGGCACCAGCGACTTGG 17 2960

BCLllA-2975 - GCTTCTCCACACCGCCC 17 2961

BCLllA-2976 + CGCCCGTGTGGCTGCGC 17 2962

BCLllA-2977 - CACGCACAGAACACTCA 17 2963

BCLllA-2978 + TGTACATGTGTAGCTGC 17 2964

BCLllA-2979 - CACCGGCGCAGCCACAC 17 2965

BCLllA-2980 + TTG CTACCTG G CTG G AA 17 2966

BCLllA-2981 + ACCCTGTCAAAG G C ACT 17 2967

BCLllA-2982 - CCACCTGGCCGAGGCCG 17 2968

BCLllA-2983 + GGGCGGATTGCAGAGGA 17 2969

BCLllA-2984 + CTAG AG A A ATC C ATG G C 17 2970

BCLllA-2985 - GGCGGAAGAGATGGCCC 17 2971

BCLllA-2986 + GGGGCGGATTGCAGAGG 17 2972

BCLllA-2987 - GTGTGGCAGTTTTCGGA 17 2973

BCLllA-2988 - GAGAGAGGCTTCCGGCC 17 2974 BCLllA-2989 + CGGGTGATGGGTGGCCA 17 2975

BCLllA-2990 - CCCGGGGAGCTGGACGG 17 2976

BCLllA-2991 - TAGGAGACTTAGAGAGC 17 2977

BCLllA-2992 + CAC ATCTTG AG CTCTCT 17 2978

BCLllA-2993 + CCTCGGCCTCGGCCAGG 17 2979

BCLllA-2994 - GGCCTTCCACCAGGTCC 17 2980

BCLllA-2995 + TCTCGCCCAGGACCTGG 17 2981

BCLllA-2996 + TCTGCCCTCTTTTGAGC 17 2982

BCLllA-2997 + ACTAAACAGGGGGGGAG 17 2983

BCLllA-2998 + CTTGACCGGGGGCTGGG 17 2984

BCLllA-2999 + TTGACCGGGGGCTGGGA 17 2985

BCLllA-3000 - AGACTTAGAGAGCTGGC 17 2986

BCLllA-3001 - AGCCCACCGCTGTCCCC 17 2987

BCLllA-3002 - AG CCATTC ACC AGTG C A 17 2988

BCLllA-3003 - GCTTCCGGCCTGGCAGA 17 2989

BCLllA-3004 - G ACTTAG AG AG CTG G C A 17 2990

BCLllA-3005 - AG GCCCAG CTCAAA AG A 17 2991

BCLllA-3006 + TCGGGTGATGGGTGGCC 17 2992

BCLllA-3007 + CAAGAGAAACCATGCAC 17 2993

BCLllA-3008 + ATCTTTG AG CTG CCTG G 17 2994

BCLllA-3009 + TATTCTTAG CAG GTTAA 17 2995

BCLllA-3010 + CTGCCCTCTTTTGAGCT 17 2996

BCLllA-3011 + CCATCTCTTCCGCCCCC 17 2997

BCLllA-3012 - TGGCCGCGGCTGCTCCC 17 2998

BCLllA-3013 + CCTGTGGCCCTCGGCCT 17 2999

BCLllA-3014 + CAGCTCCCCGGGCGGTG 17 3000

BCLllA-3015 + TTTG CAT AG G G CTG G G C 17 3001

BCLllA-3016 + GGCCCTCGGCCTCGGCC 17 3002

BCLllA-3017 - GCTGACGGAGAGCGAGA 17 3003

BCLllA-3018 - AGATGTGTGGCAGTTTT 17 3004

BCLllA-3019 + ATTCTTAG CAG GTTAAA 17 3005

BCLllA-3020 + TCTCCTAGAGAAATCCA 17 3006

BCLllA-3021 - CCTTTGACAGGGTGCTG 17 3007

BCLllA-3022 + GGAGGGGCGGATTGCAG 17 3008

BCLllA-3023 + TTCTTAG CAG GTTAAAG 17 3009

BCLllA-3024 + CGGATTGCAGAGGAGGG 17 3010

BCLllA-3025 + TTTG AG CTGGGCCTGCC 17 3011

BCLllA-3026 + CTTCAG CTTG CTGG CCT 17 3012

BCLllA-3027 + CTTGAACTTGGCCACCA 17 3013

BCLllA-3028 - CTGCAACCATTCCAGCC 17 3014

BCLllA-3029 - CATAGAGCGCCTGGGGG 17 3015

BCLllA-3030 - GGGCGCGGTCGTGGGCG 17 3016 BCLllA-3031 + TCCCATGGAGAGGTGGC 17 3017

BCLllA-3032 - GGCCGCGGCTGCTCCCC 17 3018

BCLllA-3033 - ATTTCAGAGCAACCTGG 17 3019

BCLllA-3034 - GCCTTCCACCAGGTCCT 17 3020

BCLllA-3035 + TGAATCCCATGGAGAGG 17 3021

BCLllA-3036 + TTGAGCTGGGCCTGCCC 17 3022

BCLllA-3037 + AGGGGCTCAGCGAGCTG 17 3023

BCLllA-3038 + AGGGCTTCTCGCCCGTG 17 3024

BCLllA-3039 - CACCGCTGTCCCCAGGC 17 3025

BCLllA-3040 - CAAATTTCAGAGCAACC 17 3026

BCLllA-3041 - AGAGAGCTCAAGATGTG 17 3027

BCLllA-3042 + AACCATGCACTGGTGAA 17 3028

BCLllA-3043 + CCTCCGTCCAGCTCCCC 17 3029

BCLllA-3044 + AGTGTCCCTGTGGCCCT 17 3030

BCLllA-3045 + CCCTCCGTCCAGCTCCC 17 3031

BCLllA-3046 + GGCCTGGGGACAGCGGT 17 3032

BCLllA-3047 + GCCCAGCAGCAG CTTTT 17 3033

BCLllA-3048 - CAG G CCC AG CTCAAA AG 17 3034

BCLllA-3049 - CTTCG G G CTG AG C CTG G 17 3035

BCLllA-3050 + CCCATGGAGAGGTGGCT 17 3036

BCLllA-3051 - CCCAGCCACCTCTCCAT 17 3037

BCLllA-3052 + GGGTTCCGGGGAGCTGG 17 3038

BCLllA-3053 + TAGGGCTGGGCCGGCCT 17 3039

BCLllA-3054 - CCTGGGGGCGGAAGAGA 17 3040

BCLllA-3055 + GCCCAGGACCTGGTGGA 17 3041

BCLllA-3056 - CGGGCTGAGCCTGGAGG 17 3042

BCLllA-3057 - ACCACGAGAACAGCTCG 17 3043

BCLllA-3058 + CGGCCTGGGGACAGCGG 17 3044

BCLllA-3059 - TCCAAAA AG CTG CTG CT 17 3045

BCLllA-3060 + G CG CC CTTCTG C C AG G C 17 3046

BCLllA-3061 - TCCCAGCCACCTCTCCA 17 3047

BCLllA-3062 - CTCCACCGCCAGCTCCC 17 3048

BCLllA-3063 + CTGGGCCTGCCCGGGCC 17 3049

BCLllA-3064 + AGGGCTGGGCCGGCCTG 17 3050

BCLllA-3065 + AACAGGGGGGGAGTGGG 17 3051

BCLllA-3066 - GGAGAACGGGGACGAGG 17 3052

BCLllA-3067 + TGATGCGCTTAGAGAAG 17 3053

BCLllA-3068 + GGATTGCAGAGGAGGGA 17 3054

BCLllA-3069 + GGCCGGCCTGGGGACAG 17 3055

BCLllA-3070 + GATTGCAGAGGAGGGAG 17 3056

BCLllA-3071 + ATTGCAGAGGAGGGAGG 17 3057

BCLllA-3072 + ACCGGGGGCTGGGAGGG 17 3058 BCLllA-3073 + TGGAGAGGTGGCTGGGA 17 3059

BCLllA-3074 + TTGCAGAGGAGGGAGGG 17 3060

BCLllA-3075 - CGGGGACGAGGAGGAAG 17 3061

BCLllA-3076 - GACGGAGAGCGAGAGGG 17 3062

BCLllA-3077 - TCCTCCCTCCCAGCCCC 17 3063

BCLllA-3078 + G CTTCAG CTTG CTGG CC 17 3064

BCLllA-3079 + TGCAGAGGAGGGAGGGG 17 3065

BCLllA-3080 + GGGCTGGGAGGGAGGAG 17 3066

BCLllA-3081 - GGAAGAGGAGGACGACG 17 3067

BCLllA-3082 + GGGGCTGGGAGGGAGGA 17 3068

BCLllA-3083 - GGAGGACGACGAGGAAG 17 3069

BCLllA-3084 - GGAGGAGGAGGAGCTGA 17 3070

BCLllA-3085 + GGGGGCTGGGAGGGAGG 17 3071

BCLllA-3086 + CTGGGAGGGAGGAGGGG 17 3072

BCLllA-3087 - CGAGGAAGAGGAAGAAG 17 3073

BCLllA-3088 - GGACGAGGAGGAAGAGG 17 3074

BCLllA-3089 - GGAAGAAGAGGAGGAAG 17 3075

BCLllA-3090 - GGAAGAGGAAGAAGAGG 17 3076

BCLllA-3091 - AGAAGAGGAGGAAGAGG 17 3077

BCLllA-3092 - AGAGGAGGAAGAGGAGG 17 3078

BCLllA-3093 - GGAGGAAGAGGAGGAGG 17 3079

BCLllA-3094 + GTCTATGCGGTCCGACTCGC 20 3080

BCLllA-3095 + TCGTCGGACTTGACCGTCAT 20 3081

BCLllA-3096 + CGTCGGACTTGACCGTCATG 20 3082

BCLllA-3097 - ATGACGGTCAAGTCCGACGA 20 3083

BCLllA-3098 - GAGTCGGACCGCATAGACGA 20 3084

BCLllA-3099 + CGGGCCCGGACCACTAATAT 20 3085

BCLllA-3100 + GTCGTCGGACTTGACCGTCA 20 3086

BCLllA-3101 + CTCTGGGTACTACGCCGAAT 20 3087

BCLllA-3102 + CTGGGTACTACGCCGAATGG 20 3088

BCLllA-3103 + CCGGGCCCGGACCACTAATA 20 3089

BCLllA-3104 - CCGCGGGTTGGTATCCCTTC 20 3090

BCLllA-3105 + TCTGGGTACTACGCCGAATG 20 3091

BCLllA-3106 + GGATACCAACCCGCGGGGTC 20 3092

BCLllA-3107 - ACGCCCCATATTAGTGGTCC 20 3093

BCLllA-3108 - CACTTGCGACGAAGACTCGG 20 3094

BCLllA-3109 + TCTCTGGGTACTACGCCGAA 20 3095

BCLllA-3110 - TAAGCGCATCAAGCTCGAGA 20 3096

BCLllA-3111 - TGCGACGAAGACTCGGTGGC 20 3097

BCLllA-3112 + CGCGCTTATGCTTCTCGCCC 20 3098

BCLllA-3113 + TGAAGGGATACCAACCCGCG 20 3099

BCLllA-3114 + GGGCCCGGACCACTAATATG 20 3100 BCLllA-3115 + CGTGTTGGGCATCGCGGCCG 20 3101

BCLllA-3116 + TCCGTGTTG GG CATCG CG G C 20 3102

BCLllA-3117 + GTCGGACTTGACCGTCATGG 20 3103

BCLllA-3118 + GCGCAAACTCCCGTTCTCCG 20 3104

BCLllA-3119 + CTCCGAGGAGTGCTCCGACG 20 3105

BCLllA-3120 + C ACG G ACTTG AG CG CG CTG C 20 3106

BCLllA-3121 - CACGCCCCATATTAGTGGTC 20 3107

BCLllA-3122 + GATACCAACCCGCGGGGTCA 20 3108

BCLllA-3123 - CAGCGCGCTCAAGTCCGTGG 20 3109

BCLllA-3124 + GGGTGCACGCGTGGTCGCAC 20 3110

BCLllA-3125 - G A AG C ATAAG CG CG G CC ACC 20 3111

BCLllA-3126 - GTGCGACCACGCGTGCACCC 20 3112

BCLllA-3127 + GAGTACACGTTCTCCGTGTT 20 3113

BCLllA-3128 + GTCTCGGTGGTGGACTAAAC 20 3114

BCLllA-3129 + CCGTTCTCCGGGATCAGGTT 20 3115

BCLllA-3130 + CGAGTACACGTTCTCCGTGT 20 3116

BCLllA-3131 - CGGAGAACGTGTACTCGCAG 20 3117

BCLllA-3132 - GGGAGCACGCCCCATATTAG 20 3118

BCLllA-3133 - CCATATTAGTGGTCCGGGCC 20 3119

BCLllA-3134 + GCCGCAGAACTCGCATGACT 20 3120

BCLllA-3135 + CGCCCCGCGAGCTGTTCTCG 20 3121

BCLllA-3136 - GCAGTGGCTCGCCGGCTACG 20 3122

BCLllA-3137 - CATATTAGTGGTCCGGGCCC 20 3123

BCLllA-3138 + CTGAAGGGATACCAACCCGC 20 3124

BCLllA-3139 + ATACCAACCCGCGGGGTCAG 20 3125

BCLllA-3140 - CAGCAGCGCGCTCAAGTCCG 20 3126

BCLllA-3141 + CGTCCCCGTTCTCCGGGATC 20 3127

BCLllA-3142 - CACCACG AG AACAG CTCG CG 20 3128

BCLllA-3143 - GCGGTTGAATCCAATGGCTA 20 3129

BCLllA-3144 - GGACACTTGCGACGAAGACT 20 3130

BCLllA-3145 + GTGTTGGGCATCGCGGCCGG 20 3131

BCLllA-3146 + CTTCGTCGCAAGTGTCCCTG 20 3132

BCLllA-3147 + CCCCAGGCGCTCTATGCGGT 20 3133

BCLllA-3148 + CCGTGTTGGGCATCGCGGCC 20 3134

BCLllA-3149 + CGTTCTCCGGGATCAGGTTG 20 3135

BCLllA-3150 + G CCTCTCTCG ATACTG ATCC 20 3136

BCLllA-3151 + TCGCATGACTTGG ACTTG AC 20 3137

BCLllA-3152 - ATCACCCGAGTGCCTTTGAC 20 3138

BCLllA-3153 - TAAGCGCGGCCACCTGGCCG 20 3139

BCLllA-3154 - GCACAAATCGTCCCCCATGA 20 3140

BCLllA-3155 - CGCCCTGCCCGACGTCATGC 20 3141

BCLllA-3156 - CAACCTGATCCCGGAGAACG 20 3142 BCLllA-3157 - CGGAGCACTCCTCGGAGAAC 20 3143

BCLllA-3158 - AGACTCGGTGGCCGGCGAGT 20 3144

BCLllA-3159 + GGCGGTGGAGAGACCGTCGT 20 3145

BCLllA-3160 - GTGTACTCG CAGTG GCTCGC 20 3146

BCLllA-3161 - TCGGAGCACTCCTCGGAGAA 20 3147

BCLllA-3162 - CCCGGCCGCGATGCCCAACA 20 3148

BCLllA-3163 + CCCGTTCTCCGGGATCAGGT 20 3149

BCLllA-3164 + TCGGTGGTGGACTAAACAGG 20 3150

BCLllA-3165 + CCTGAAGGGATACCAACCCG 20 3151

BCLllA-3166 + GTCGTTCTCG CTCTTG AACT 20 3152

BCLllA-3167 - CCCCACCGCATAGAGCGCCT 20 3153

BCLllA-3168 + GTCGCTGGTGCCGGGTTCCG 20 3154

BCLllA-3169 - CGAGAACAGCTCGCGGGGCG 20 3155

BCLllA-3170 + CGCATGACTTGGACTTGACC 20 3156

BCLllA-3171 - CCCACCGCATAGAGCGCCTG 20 3157

BCLllA-3172 + AAGTCGCTGGTGCCGGGTTC 20 3158

BCLllA-3173 + CGAGGAGTGCTCCGACGAGG 20 3159

BCLllA-3174 - TCCCCGGGCGAGTCGGCCTC 20 3160

BCLllA-3175 - CTCCCCGGGCGAGTCGGCCT 20 3161

BCLllA-3176 + CATGACTTGGACTTGACCGG 20 3162

BCLllA-3177 - AGCTCGCGGGGCGCGGTCGT 20 3163

BCLllA-3178 + TGCTCCGACGAGGAGGCAAA 20 3164

BCLllA-3179 + CTTTTTGGACAGGCCCCCCG 20 3165

BCLllA-3180 - CTACGGCTTCGGGCTGAGCC 20 3166

BCLllA-3181 - CCCCGGGCGAGTCGGCCTCG 20 3167

BCLllA-3182 + TAA CAGTG CCATCGTCTATG 20 3168

BCLllA-3183 - CTCCTCGTCGGAGCACTCCT 20 3169

BCLllA-3184 - CCCGGCACCAGCGACTTGGT 20 3170

BCLllA-3185 - GCGCTTCTCCACACCGCCCG 20 3171

BCLllA-3186 + CTCGGTGGTGGACTAAACAG 20 3172

BCLllA-3187 - CCCCCACCGCATAGAGCGCC 20 3173

BCLllA-3188 - GATCCCGGAGAACGGGGACG 20 3174

BCLllA-3189 + CCAGGCGCTCTATGCGGTGG 20 3175

BCLllA-3190 - TTAGTGGTCCGGGCCCGGGC 20 3176

BCLllA-3191 + CCCAGGCGCTCTATGCGGTG 20 3177

BCLllA-3192 - CGGCTGCTCCCCGGGCGAGT 20 3178

BCLllA-3193 - TCGCCGGCTACGCGGCCTCC 20 3179

BCLllA-3194 - ATCGAGAGAGGCTTCCGGCC 20 3180

BCLllA-3195 + GGGTCCAAGTGATGTCTCGG 20 3181

BCLllA-3196 - ATCGCCTTTTGCCTCCTCGT 20 3182

BCLllA-3197 - ATCTCGGGGCGCAGCGGCAC 20 3183

BCLllA-3198 + CGGTGGTGGACTAAACAGGG 20 3184 BCLllA-3199 - GATGGCACTGTTAATGGCCG 20 3185

BCLllA-3200 + TGCCCTGCATGACGTCGGGC 20 3186

BCLllA-3201 + TCTCGGTGGTGGACTAAACA 20 3187

BCLllA-3202 - AGAGGGTGGACTACGGCTTC 20 3188

BCLllA-3203 + CCCCGAGGCCGACTCGCCCG 20 3189

BCLllA-3204 - GATCTCGGGGCGCAGCGGCA 20 3190

BCLllA-3205 - ACGGAAGTCCCCTGACCCCG 20 3191

BCLllA-3206 + ACTCGCCCGGGGAGCAGCCG 20 3192

BCLllA-3207 - TTG CG CTTCTCCAC ACCG CC 20 3193

BCLllA-3208 - GGAACCCGGCACCAGCGACT 20 3194

BCLllA-3209 + GCATGACTTGGACTTGACCG 20 3195

BCLllA-3210 - TAATGGCCGCGGCTGCTCCC 20 3196

BCLllA-3211 - CCGGGCGAGTCGGCCTCGGG 20 3197

BCLllA-3212 + GTCAAAGG CACTCG G GTG AT 20 3198

BCLllA-3213 - G GTG CTG CG GTTG A ATC C A A 20 3199

BCLllA-3214 - CTGGGCGAGAAGCATAAGCG 20 3200

BCLllA-3215 + ACTTGGACTTGACCGGGGGC 20 3201

BCLllA-3216 + CCCCCCGAGGCCGACTCGCC 20 3202

BCLllA-3217 - CCACCGCATAGAGCGCCTGG 20 3203

BCLllA-3218 + AGTCGCTGGTGCCGGGTTCC 20 3204

BCLllA-3219 + TCGCACAGGTTGCACTTGTA 20 3205

BCLllA-3220 + GCCCTGCATGACGTCGGGCA 20 3206

BCLllA-3221 + CCGCCCCCAGGCGCTCTATG 20 3207

BCLllA-3222 - GCCCTGCCCGACGTCATGCA 20 3208

BCLllA-3223 + GTCGCACAG GTTG CACTTGT 20 3209

BCLllA-3224 - AGGTAGCAAGCCGCCCTTCC 20 3210

BCLllA-3225 - CCAACCTGATCCCGGAGAAC 20 3211

BCLllA-3226 + AGGAAGGGCGGCTTGCTACC 20 3212

BCLllA-3227 - GAAGGAGTTCGACCTGCCCC 20 3213

BCLllA-3228 + CTTGGACTTGACCGGGGGCT 20 3214

BCLllA-3229 - GAGAGGGTGGACTACGGCTT 20 3215

BCLllA-3230 - TCCAAGTCATGCGAGTTCTG 20 3216

BCLllA-3231 - ACCCGGCACCAGCGACTTGG 20 3217

BCLllA-3232 + CCCCCAGGCGCTCTATGCGG 20 3218

BCLllA-3233 + GCGTCTGCCCTCTTTTGAGC 20 3219

BCLllA-3234 - GCCCGACGTCATGCAGGGCA 20 3220

BCLllA-3235 + GAGCTTGATGCGCTTAGAGA 20 3221

BCLllA-3236 - CAGCTCGCGGGGCGCGGTCG 20 3222

BCLllA-3237 + CGTGGTGGCGCGCCGCCTCC 20 3223

BCLllA-3238 - TCACCCGAGTGCCTTTGACA 20 3224

BCLllA-3239 - GAACGACCCCAACCTGATCC 20 3225

BCLllA-3240 + CAACCGCAGCACCCTGTCAA 20 3226 BCLllA-3241 + TCCAAGTGATGTCTCGGTGG 20 3227

BCLllA-3242 + GTTCTCCGTGTTGGGCATCG 20 3228

BCLllA-3243 - CGGAAGTCCCCTGACCCCGC 20 3229

BCLllA-3244 + TATGCTTCTCGCCCAGGACC 20 3230

BCLllA-3245 - AGCTGGACGGAGGGATCTCG 20 3231

BCLllA-3246 + GGCTGCGCCGGTGCACCACC 20 3232

BCLllA-3247 - GTTG GTATCCCTTCAG G ACT 20 3233

BCLllA-3248 - ATAGACGATGGCACTGTTAA 20 3234

BCLllA-3249 - CTCCCGCCATGGATTTCTCT 20 3235

BCLllA-3250 - ACCAGGATCAGTATCGAGAG 20 3236

BCLllA-3251 - AGTCCCCTGACCCCGCGGGT 20 3237

BCLllA-3252 + GTCTGGAGTCTCCGAAGCTA 20 3238

BCLllA-3253 - GCCGGCCCAG C CCTATG C A A 20 3239

BCLllA-3254 - GATGTGTGGCAGTTTTCGGA 20 3240

BCLllA-3255 + CTAGAGAAATCCATGGCGGG 20 3241

BCLllA-3256 + GGCGCTGCCCACCAAGTCGC 20 3242

BCLllA-3257 - CCCGGGCGAGTCGGCCTCGG 20 3243

BCLllA-3258 - ACACCGCCCGGGGAGCTGGA 20 3244

BCLllA-3259 + CAGTAACCTTTGCATAGGGC 20 3245

BCLllA-3260 - TCAGTATCGAGAGAGGCTTC 20 3246

BCLllA-3261 + GCATGACGTCGGGCAGGGCG 20 3247

BCLllA-3262 - C CG CAT AG AG CGCCTGGGGG 20 3248

BCLllA-3263 + CCCCCGAGGCCGACTCGCCC 20 3249

BCLllA-3264 + AGGGCGGCTTGCTACCTGGC 20 3250

BCLllA-3265 + GCACCCTGTCAAAGGCACTC 20 3251

BCLllA-3266 + CTG ATC CTG GTATTCTT AG C 20 3252

BCLllA-3267 + CATGTGGCGCTTCAGCTTGC 20 3253

BCLllA-3268 + CCCACCAAGTCGCTGGTGCC 20 3254

BCLllA-3269 + GGAGGCAAAAGGCGATTGTC 20 3255

BCLllA-3270 - CCCAACCTGATCCCGGAGAA 20 3256

BCLllA-3271 + GAGTCTCCGAAGCTAAGGAA 20 3257

BCLllA-3272 - GGCTATGGAGCCTCCCGCCA 20 3258

BCLllA-3273 + CGTCTGCCCTCTTTTGAGCT 20 3259

BCLllA-3274 - CGCCCGGGGAGCTGGACGGA 20 3260

BCLllA-3275 + AGTAACCTTTGCATAGGGCT 20 3261

BCLllA-3276 - TCCACCACCGAGACATCACT 20 3262

BCLllA-3277 + GGTTGCAGTAACCTTTGCAT 20 3263

BCLllA-3278 + G C A AT ATG A ATC CC ATG GAG 20 3264

BCLllA-3279 + ACCATGCCCTGCATGACGTC 20 3265

BCLllA-3280 + GGCCTCGCTGAAGTGCTGCA 20 3266

BCLllA-3281 - AGAGCAACCTGGTGGTGCAC 20 3267

BCLllA-3282 + GCCCACCAAGTCGCTGGTGC 20 3268 BCLllA-3283 + TGTCAAAGGCACTCGGGTGA 20 3269

BCLllA-3284 + AGCTTGATGCGCTTAGAGAA 20 3270

BCLllA-3285 + AGGGGGGGCGTCGCCAGGAA 20 3271

BCLllA-3286 + GTGGAAAGCGCCCTTCTGCC 20 3272

BCLllA-3287 + TGGGGGTCCAAGTGATGTCT 20 3273

BCLllA-3288 - CTCCATG CAG CACTTCAG CG 20 3274

BCLllA-3289 + G CG CTTC AG CTTG CTG G C CT 20 3275

BCLllA-3290 - CTTCAGCGAGGCCTTCCACC 20 3276

BCLllA-3291 + GGAGTCTCCGAAGCTAAGGA 20 3277

BCLllA-3292 + CACTCGGGTGATGGGTGGCC 20 3278

BCLllA-3293 - TGCGCTTCTCCACACCGCCC 20 3279

BCLllA-3294 + GGTGGTGGACTAAACAGGGG 20 3280

BCLllA-3295 - CGAGGCCTTCCACCAGGTCC 20 3281

BCLllA-3296 - AATGGCCGCGGCTGCTCCCC 20 3282

BCLllA-3297 + GTTGTACATGTGTAG CTG CT 20 3283

BCLllA-3298 - GTTCTTCACACACCCCCATT 20 3284

BCLllA-3299 - CGCAGCGGCACGGGAAGTGG 20 3285

BCLllA-3300 + GCGGGAGG CTCC ATAG C CAT 20 3286

BCLllA-3301 - GGTGCACCGGCGCAGCCACA 20 3287

BCLllA-3302 - CTCCACACCGCCCGGGGAGC 20 3288

BCLllA-3303 + A AAG CG CCCTTCTG CC AG G C 20 3289

BCLllA-3304 + ACTCGGGTGATGGGTGGCCA 20 3290

BCLllA-3305 + CTGCCTGGAGGCCGCGTAGC 20 3291

BCLllA-3306 + GTCCAGCTCCCCGGGCGGTG 20 3292

BCLllA-3307 - GAG CTG G A CG G AG G G ATCTC 20 3293

BCLllA-3308 - TCTAGCCCACCGCTGTCCCC 20 3294

BCLllA-3309 + AGTTGTACATGTGTAG CTG C 20 3295

BCLllA-3310 + ATTCTGCACCTAGTCCTGAA 20 3296

BCLllA-3311 - CCACCACGAGAACAGCTCGC 20 3297

BCLllA-3312 + CTCCTAGAGAAATCCATGGC 20 3298

BCLllA-3313 - TTTAACCTG CTAAG AATACC 20 3299

BCLllA-3314 + GGACTAAACAGGGGGGGAGT 20 3300

BCLllA-3315 - GGCCACCTGGCCGAGGCCGA 20 3301

BCLllA-3316 + G G CTTG CTAC CTG G CTG G A A 20 3302

BCLllA-3317 + CATTCTGCACCTAGTCCTGA 20 3303

BCLllA-3318 + TGCTGGCCTGGGTGCACGCG 20 3304

BCLllA-3319 + TGTGGCCCTCGGCCTCGGCC 20 3305

BCLllA-3320 - CCGCCCGGGGAGCTGGACGG 20 3306

BCLllA-3321 - TGGCCGAGGCCGAGGGCCAC 20 3307

BCLllA-3322 + TGGGCATCGCGGCCGGGGGC 20 3308

BCLllA-3323 + TCTCCTAGAGAAATCCATGG 20 3309

BCLllA-3324 + GGGCCATCTCTTCCGCCCCC 20 3310 BCLllA-3325 + GTTGCAGTAACU 1 I GCATA 20 3311

BCLllA-3326 + AAAGGCACTCGGGTGATGGG 20 3312

BCLllA-3327 + GAAGGGATCTTTGAGCTGCC 20 3313

BCLllA-3328 + G CC ACAC ATCTTG AG CTCTC 20 3314

BCLllA-3329 - GGAGGGATCTCGGGGCGCAG 20 3315

BCLllA-3330 - CCCGGAGAACGGGGACGAGG 20 3316

BCLllA-3331 + TGCATAGGGCTGGGCCGGCC 20 3317

BCLllA-3332 - CGGGGCGCGGTCGTGGGCGT 20 3318

BCLllA-3333 + GAGGGGGGGCGTCGCCAGGA 20 3319

BCLllA-3334 - ACCGCCAGCTCCCCGGAACC 20 3320

BCLllA-3335 + G GTATTCTTAG CAG GTTAAA 20 3321

BCLllA-3336 - AGGCTTCCGGCCTGGCAGAA 20 3322

BCLllA-3337 + GATCCCTCCGTCCAGCTCCC 20 3323

BCLllA-3338 + TGGTATTCTTAGCAGGTTAA 20 3324

BCLllA-3339 - ATCT ACTTAG A A AG CG A AC A 20 3325

BCLllA-3340 - CGGCCACCTGGCCGAGGCCG 20 3326

BCLllA-3341 - CAACACG CACAG AACACTCA 20 3327

BCLllA-3342 + GCCGGCCTGGGGACAGCGGT 20 3328

BCLllA-3343 - GCCACCACGAGAACAGCTCG 20 3329

BCLllA-3344 + GTATTCTTAGCAGGTTAAAG 20 3330

BCLllA-3345 - CTCTAGGAGACTTAGAGAGC 20 3331

BCLllA-3346 - AACAG CC ATTC ACC AGTG CA 20 3332

BCLllA-3347 + TTGCAAGAGAAACCATGCAC 20 3333

BCLllA-3348 + GACTTGACCGGGGGCTGGGA 20 3334

BCLllA-3349 + ACCTTTGCATAGGGCTGGGC 20 3335

BCLllA-3350 + TCTTTTGAGCTGGGCCTGCC 20 3336

BCLllA-3351 - GAGGCCTTCCACCAGGTCCT 20 3337

BCLllA-3352 + CTTTTGAGCTGGGCCTGCCC 20 3338

BCLllA-3353 + GGGATCTTTGAGCTGCCTGG 20 3339

BCLllA-3354 - GGGCAGGCCCAGCTCAAAAG 20 3340

BCLllA-3355 + AG C ACCCTGTC AAAG G CACT 20 3341

BCLllA-3356 + TGGACTAAACAGGGGGGGAG 20 3342

BCLllA-3357 + GCTCTTGAACTTGGCCACCA 20 3343

BCLllA-3358 + GAATCCCATGGAGAGGTGGC 20 3344

BCLllA-3359 - GTGCACCGGCGCAGCCACAC 20 3345

BCLllA-3360 - AAAG ATC CCTTC CTTAG CTT 20 3346

BCLllA-3361 + TGTCTGCAATATGAATCCCA 20 3347

BCLllA-3362 - GGCAGGCCCAGCTCAAAAGA 20 3348

BCLllA-3363 + CCTCCGTCCAGCTCCCCGGG 20 3349

BCLllA-3364 - CTGTCC AAAAAG CTG CTG CT 20 3350

BCLllA-3365 + G CTTGATG CG CTTAG AG AAG 20 3351

BCLllA-3366 - CGGCTTCGGGCTGAGCCTGG 20 3352 BCLllA-3367 + C ACC ATG CCCTG CATGACGT 20 3353

BCLllA-3368 - 1 CAAGA 1 1 1 GCA 1 1 1 1 20 3354

BCLllA-3369 - GTTC AAATTTC AG AG CAACC 20 3355

BCLllA-3370 + GAGAAGGGGCTCAGCGAGCT 20 3356

BCLllA-3371 - GCAGCGGCACGGGAAGTGGA 20 3357

BCLllA-3372 + AAGTCTCCTAGAGAAATCCA 20 3358

BCLllA-3373 + GGTGCCGGGTTCCGGGGAGC 20 3359

BCLllA-3374 - CCTGTCCAAAAAG CTG CTG C 20 3360

BCLllA-3375 + ATATGAATCCCATGGAGAGG 20 3361

BCLllA-3376 - GGGCGCAGCGGCACGGGAAG 20 3362

BCLllA-3377 - GGCCGAGGCCGAGGGCCACA 20 3363

BCLllA-3378 + GCAAGTGTCCCTGTGGCCCT 20 3364

BCLllA-3379 + GGACTTGACCGGGGGCTGGG 20 3365

BCLllA-3380 + GCTTCTCGCCCAGGACCTGG 20 3366

BCLllA-3381 - GCGCCTGGGGGCGGAAGAGA 20 3367

BCLllA-3382 + GTCCCTGTGGCCCTCGGCCT 20 3368

BCLllA-3383 + ATCCCTCCGTCCAGCTCCCC 20 3369

BCLllA-3384 - GTGCCTTTGACAGGGTGCTG 20 3370

BCLllA-3385 - CCCAGAGAGCTCAAGATGTG 20 3371

BCLllA-3386 + GGCCCTCGGCCTCGGCCAGG 20 3372

BCLllA-3387 - GAGAGCGAGAGGGTGGACTA 20 3373

BCLllA-3388 + GGGGGCGTCGCCAGGAAGGG 20 3374

BCLllA-3389 + AGAGAAGGGGCTCAGCGAGC 20 3375

BCLllA-3390 + CC ACAC ATCTTG AG CTCTCT 20 3376

BCLllA-3391 + GCTGCCCAGCAGCAG CTTTT 20 3377

BCLllA-3392 - GGAGCTGGACGGAGGGATCT 20 3378

BCLllA-3393 - GGGGGCGGAAGAGATGGCCC 20 3379

BCLllA-3394 - AGGAGACTTAGAGAGCTGGC 20 3380

BCLllA-3395 - GAGGCTTCCGGCCTGGCAGA 20 3381

BCLllA-3396 + AATCCCATGGAGAGGTGGCT 20 3382

BCLllA-3397 + TGTG CATGTG CGTCTTCATG 20 3383

BCLllA-3398 + CTCGCCCAGGACCTGGTGGA 20 3384

BCLllA-3399 + TCCTCCTCGTCCCCGTTCTC 20 3385

BCLllA-3400 + AGAAACCATGCACTGGTGAA 20 3386

BCLllA-3401 - CTTCGGGCTGAGCCTGGAGG 20 3387

BCLllA-3402 + GCCGGGTTCCGGGGAGCTGG 20 3388

BCLllA-3403 + AGAAGGGGCTCAGCGAGCTG 20 3389

BCLllA-3404 + CTAAACAGGGGGGGAGTGGG 20 3390

BCLllA-3405 - CAAATTTCAGAGCAACCTGG 20 3391

BCLllA-3406 + GAGGGAGGGGGGGCGTCGCC 20 3392

BCLllA-3407 + CCTCCTCGTCCCCGTTCTCC 20 3393

BCLllA-3408 + CCAGCAGCAGCTTTTTGGAC 20 3394 BCLllA-3409 - GCCCACCGCTGTCCCCAGGC 20 3395

BCLllA-3410 - GGAGACTTAGAGAGCTGGCA 20 3396

BCLllA-3411 - AGGAGCTGACGGAGAGCGAG 20 3397

BCLllA-3412 + GAGGGGCGGATTGCAGAGGA 20 3398

BCLllA-3413 + C ATAG GGCTGGGCCGGCCTG 20 3399

BCLllA-3414 + GGCGGATTGCAGAGGAGGGA 20 3400

BCLllA-3415 + GGAGGGGCGGATTGCAGAGG 20 3401

BCLllA-3416 - TTACTGCAACCATTCCAGCC 20 3402

BCLllA-3417 + GCATAGGGCTGGGCCGGCCT 20 3403

BCLllA-3418 + GGGCGGATTGCAGAGGAGGG 20 3404

BCLllA-3419 + GGGTTCCGGGGAGCTGGCGG 20 3405

BCLllA-3420 + TCTCGCCCGTGTGGCTGCGC 20 3406

BCLllA-3421 - CTTCCCAGCCACCTCTCCAT 20 3407

BCLllA-3422 - GCTGACGGAGAGCGAGAGGG 20 3408

BCLllA-3423 + GCGGATTGCAGAGGAGGGAG 20 3409

BCLllA-3424 - GGAGCTGACGGAGAGCGAGA 20 3410

BCLllA-3425 - TCTCTCCACCGCCAGCTCCC 20 3411

BCLllA-3426 + TTGACCGGGGGCTGGGAGGG 20 3412

BCLllA-3427 + CGGATTGCAGAGGAGGGAGG 20 3413

BCLllA-3428 - GCGGGGCGCGGTCGTGGGCG 20 3414

BCLllA-3429 + GAGCTGGGCCTGCCCGGGCC 20 3415

BCLllA-3430 + CTGGGCCGGCCTGGGGACAG 20 3416

BCLllA-3431 + TGTAGGGCTTCTCGCCCGTG 20 3417

BCLllA-3432 + CCATGGAGAGGTGGCTGGGA 20 3418

BCLllA-3433 + GGAGGAGGGGCGGATTGCAG 20 3419

BCLllA-3434 - CCTTCCCAGCCACCTCTCCA 20 3420

BCLllA-3435 + CCCGCGAGCTGTTCTCGTGG 20 3421

BCLllA-3436 + GATTGCAGAGGAGGGAGGGG 20 3422

BCLllA-3437 + GGCCGGCCTGGGGACAGCGG 20 3423

BCLllA-3438 + GGATTGCAGAGGAGGGAGGG 20 3424

BCLllA-3439 + ACCGGGGGCTGGGAGGGAGG 20 3425

BCLllA-3440 + CCGGGGGCTGGGAGGGAGGA 20 3426

BCLllA-3441 - GAACGGGGACGAGGAGGAAG 20 3427

BCLllA-3442 - CCCTCCTCCCTCCCAGCCCC 20 3428

BCLllA-3443 + CGGGGGCTGGGAGGGAGGAG 20 3429

BCLllA-3444 + G G CG CTTC AG CTTG CTG G CC 20 3430

BCLllA-3445 - CGGGGACGAGGAGGAAGAGG 20 3431

BCLllA-3446 - AGAGGAGGAGGAGGAGCTGA 20 3432

BCLllA-3447 + GGGCTGGGAGGGAGGAGGGG 20 3433

BCLllA-3448 - AGAGGAGGACGACGAGGAAG 20 3434

BCLllA-3449 - CGACGAGGAAGAGGAAGAAG 20 3435

BCLllA-3450 - GGAGGAAGAGGAGGACGACG 20 3436 BCLllA-3451 - CGAGGAAGAGGAAGAAGAGG 20 3437

BCLllA-3452 - GGAAGAAGAGGAGGAAGAGG 20 3438

BCLllA-3453 - AGAGGAAGAAGAGGAGGAAG 20 3439

BCLllA-3454 - AGAAGAGGAGGAAGAGGAGG 20 3440

BCLllA-3455 - AGAGGAGGAAGAGGAGGAGG 20 3441

Table 4A provides exemplary targeting domains for knocking out the BCL11A gene by targeting the early coding sequence the BCL11A gene selected according to first tier parameters. The targeting domains are within first 500bp of coding sequence downstream of start codon, good orthogonality, start with G. 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 generates a double strand break (Cas9 nuclease) or a single-strand break (Cas9 nickase). In an embodiment, dual targeting is used to create two double strand breaks to remove the enhancer region in the BCL11A gene, e.g., the first gRNA is used to target upstream (i.e., 5') of the enhancer region in the BCL11A gene and the second gRNA is used to target downstream (i.e., 3') of the enhancer region in the BCL11A gene.

Any of the targeting domains in the table can be used with a S. aureus Cas9 (nickase) molecule to generate a single strand break. 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 4A

BCLllA-3459 - GATTGTTTATCAACGTCATC 20 3445

BCLllA-3460 + GCACTCATCCCAGGCGT 17 3446

BCLllA-3461 + GGGGATTAGAGCTCCATGTG 20 3447

BCLllA-3462 - GTGCAGAATATGCCCCG 17 3448

Table 4B provides exemplary targeting domains for knocking out the BCL11A gene by targeting the early coding sequence the BCL11A gene selected according to second tier parameters. The targeting domains are within first 500bp of coding sequence downstream of start codon, good orthogonality, and do not start with G. 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 generates a double strand break (Cas9 nuclease) or a single-strand break (Cas9 nickase). In an embodiment, dual targeting is used to create two double strand breaks to remove the enhancer region in the BCL11A gene, e.g., the first gRNA is used to target upstream (i.e., 5') of the enhancer region in the BCL11A gene and the second gRNA is used to target downstream (i.e., 3') of the enhancer region in the BCL11A gene.

Table 4B

BCLllA-3464 + AATTCCCGTTTGCTTAAGTG 20 3450

BCLllA-3465 - ACCAGACCACGGCCCGT 17 3451

BCLllA-3466 - ATGAACCAGACCACGGCCCG 20 3452

BCLllA-3467 + ATTCCCGTTTGCTTAAGTGC 20 3453

BCLllA-3468 - CCAGACCACGGCCCGTT 17 3454

BCLllA-3469 + CCCGTTTGCTTAAGTGC 17 3455

BCLllA-3470 + CCTGGATGCCAACCTCC 17 3456

BCLllA-3471 + CTGGATGCCAACCTCCA 17 3457

BCLllA-3472 + TCATCCTCTGGCGTGAC 17 3458

BCLllA-3473 + TCCCGTTTGCTTAAGTG 17 3459

BCLllA-3474 + TCGTCATCCTCTGGCGTGAC 20 3460

BCLllA-3475 + TCTG CACTCATCCCAGG CGT 20 3461

BCLllA-3476 + TCTG GTTC ATC ATCTGT 17 3462

BCLllA-3477 - TGAACCAGACCACGGCCCGT 20 3463

BCLllA-3478 + TGACCTGGATGCCAACCTCC 20 3464

BCLllA-3479 - TGAGTGCAGAATATGCCCCG 20 3465

BCLllA-3480 + TG CACTCATCCCAGG CG 17 3466

BCLllA-3481 + TGGTCTGGTTCATCATCTGT 20 3467

BCLllA-3482 - TGTTTATCAACGTCATC 17 3468

BCLllA-3483 - TGTTTATCAACGTCATCTAG 20 3469

BCLllA-3484 - TTATCAACGTCATCTAG 17 3470

BCLllA-3485 + TTCTGCACTCATCCCAGGCG 20 3471

BCLllA-3486 - TTGTTTATCAACGTCATCTA 20 3472

BCLllA-3487 - TTTATCAACGTCATCTA 17 3473

Table 4C provides exemplary targeting domains for knocking out the BCL11A gene by targeting the early coding sequence the BCL11A gene selected according to third tier parameters. The targeting domains are within first 500bp of coding sequence downstream of start codon and start with G. 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 generates a double strand break (Cas9 nuclease) or a single- strand break (Cas9 nickase). In an embodiment, dual targeting is used to create two double strand breaks to remove the enhancer region in the BCL11A gene, e.g., the first gRNA is used to target upstream (i.e., 5') of the enhancer region in the BCL11A gene and the second gRNA is used to target downstream (i.e., 3') of the enhancer region in the BCL11A gene.

Table 4C

Table 4D provides exemplary targeting domains for knocking out the BCLllA gene by targeting the early coding sequence the BCLllA gene selected according to forth tier parameters. The targeting domains are within first 500bp of coding sequence downstream of start codon and do not start with G. 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 generates a double strand break (Cas9 nuclease) or a single-strand break (Cas9 nickase). In an embodiment, dual targeting is used to create two double strand breaks to remove the enhancer region in the BCLllA gene, e.g., the first gRNA is used to target upstream (i.e., 5') of the enhancer region in the BCLllA gene and the second gRNA is used to target downstream (i.e., 3') of the enhancer region in the BCLllA gene.

Table 4D

BCLllA-3521 + AATAAGAATGTCCCCCA 17 3507

BCLllA-3522 - ACCCC AG C ACTTAAG CAAAC 20 3508

BCLllA-3523 - ACCTTCCCCTTCACCAA 17 3509

BCLllA-3524 + AGAGCTCCATGTGCAGA 17 3510

BCLllA-3525 + AGAGCTCCATGTGCAGAACG 20 3511

BCLllA-3526 - AGATGAACTTCCCATTG 17 3512

BCLllA-3527 - AG CCATTCTTACAG ATG 17 3513

BCLllA-3528 + AGCTCCATGTGCAGAAC 17 3514

BCLllA-3529 + AGCTCCATGTGCAGAACGAG 20 3515

BCLllA-3530 - AGCTCTAATCCCCACGC 17 3516

BCLllA-3531 - AGGAATTTGCCCCAAAC 17 3517

BCLllA-3532 + AGGAGGTCATGATCCCCTTC 20 3518

BCLllA-3533 + AGGTCATGATCCCCTTC 17 3519

BCLllA-3534 - AGTGCCAGATGAACTTCCCA 20 3520

BCLllA-3535 + ATAAGAATGTCCCCCAA 17 3521

BCLllA-3536 + ATCCCAGGCGTGGGGAT 17 3522

BCLllA-3537 + ATCCCCTTCTGGAGCTCCCA 20 3523

BCLllA-3538 + ATCTGG CACTG CCCACAGGT 20 3524

BCLllA-3539 - ATG CAATG G CAG CCTCTG CT 20 3525

BCLllA-3540 + ATGTGCAGAACGAGGGG 17 3526

BCLllA-3541 + ATTAGAGCTCCATGTGCAGA 20 3527

BCLllA-3542 + ATTCTG CACTC ATCCC AG G C 20 3528

BCLllA-3543 - A l l l l 1 A l CGAGCACAA 17 3529

BCLllA-3544 - CAATGG CAG CCTCTG CT 17 3530

BCLllA-3545 - CACGCCTGGGATGAGTG 17 3531

BCLllA-3546 - CAGATGAACTTCCCATT 17 3532

BCLllA-3547 + CATCTCGATTGGTGAAG 17 3533

BCLllA-3548 + CATGTGCAGAACGAGGG 17 3534

BCLllA-3549 + CATGTGCAGAACGAGGGGAG 20 3535

BCLllA-3550 + CC ACAG CTTTTTCTAAG 17 3536

BCLllA-3551 - CCACGGCCCGTTGGGAGCTC 20 3537

BCLllA-3552 - CCAGATGAACTTCCCAT 17 3538

BCLllA-3553 - CCAGC ACTTAAG CAAAC 17 3539

BCLllA-3554 - CCCAGCACTTAAGCAAA 17 3540

BCLllA-3555 - CCCCACGCCTGGGATGAGTG 20 3541

BCLllA-3556 - CCCCAGCACTTAAGCAA 17 3542

BCLllA-3557 - CCCCTTCACCAATCGAG 17 3543

BCLllA-3558 - CCCGTTGGGAGCTCCAG 17 3544

BCLllA-3559 + CCCTTCTGGAGCTCCCA 17 3545

BCLllA-3560 - CCGTTGGGAGCTCCAGA 17 3546

BCLllA-3561 - CCTGTGGGCAGTGCCAG 17 3547

BCLllA-3562 - CGGCCCGTTGGGAGCTC 17 3548 BCLllA-3563 - CGGCCCGTTGGGAGCTCCAG 20 3549

BCLllA-3564 - CGTTG G G AG CTC C AG A A 17 3550

BCLllA-3565 + CGTTTGTG CTCG ATAAAAAT 20 3551

BCLllA-3566 - CTAGAGGAATTTGCCCCAAA 20 3552

BCLllA-3567 + CTCATCCCAGGCGTGGGGAT 20 3553

BCLllA-3568 + CTCCATGTGCAGAACGA 17 3554

BCLllA-3569 + CTCCATGTGCAGAACGAGGG 20 3555

BCLllA-3570 - CTCCCCTCGTTCTGCAC 17 3556

BCLllA-3571 - CTCCTCCCCTCGTTCTGCAC 20 3557

BCLllA-3572 - CTCTAATCCCCACGCCTGGG 20 3558

BCLllA-3573 + CTGCACTCATCCCAGGC 17 3559

BCLllA-3574 - CTTATTTTTATCGAGCACAA 20 3560

BCLllA-3575 - CTTCCCCTTCACCAATCGAG 20 3561

BCLllA-3576 + TAAGAATGTCCCCCAAT 17 3562

BCLllA-3577 - TAATCCCCACGCCTGGG 17 3563

BCLllA-3578 + TAG AG CTC C ATGTG C AG A A C 20 3564

BCLllA-3579 - TAGAGGAATTTGCCCCAAAC 20 3565

BCLllA-3580 + TATCCACAG CTTTTTCTAAG 20 3566

BCLllA-3581 - TCACCTGTGGGCAGTGCCAG 20 3567

BCLllA-3582 + TCATCTCGATTGGTGAA 17 3568

BCLllA-3583 + TCATCTG G C ACTG CCC AC AG 20 3569

BCLllA-3584 + TC ATCTGTA AG A ATG GCTTC 20 3570

BCLllA-3585 - TCATGACCTCCTCACCT 17 3571

BCLllA-3586 + TCCATGTGCAGAACGAG 17 3572

BCLllA-3587 + TCCATGTGCAGAACGAGGGG 20 3573

BCLllA-3588 - TCCCCTCGTTCTGCACA 17 3574

BCLllA-3589 - TCCTCCCCTCGTTCTGCACA 20 3575

BCLllA-3590 - TCTG CTTAG AAAAAG CT 17 3576

BCLllA-3591 + TCTG G C ACTG CCC ACAG 17 3577

BCLllA-3592 + TCTGGCACTGCCCACAGGTG 20 3578

BCLllA-3593 + TCTGTAAG AATG GCTTC 17 3579

BCLllA-3594 - TGAAAAAAGCATCCAATCCC 20 3580

BCLllA-3595 - TGAAGCCATTCTTACAGATG 20 3581

BCLllA-3596 + TGCCAACCTCCACGGGA 17 3582

BCLllA-3597 - TGCCAGATGAACTTCCCATT 20 3583

BCLllA-3598 + TG CTTTTTTCATCTCG ATTG 20 3584

BCLllA-3599 - TGGAGCTCTAATCCCCACGC 20 3585

BCLllA-3600 + TGGCACTGCCCACAGGT 17 3586

BCLllA-3601 - TGGCATCCAGGTCACGC 17 3587

BCLllA-3602 + TGGGGTTTGCCTTGCTTGCG 20 3588

BCLllA-3603 - 1 I A I 1 1 1 1 A I A A AAA 20 3589

BCLllA-3604 + TTCATCTCGATTGGTGA 17 3590 BCLllA-3605 - TTGGCATCCAGGTCACGCCA 20 3591

BCLllA-3606 + TTGTG CTCG ATAAAAAT 17 3592

BCLllA-3607 + TTTCATCTCGATTGGTG 17 3593

BCLllA-3608 + TTTCATCTCGATTGGTGAAG 20 3594

BCLllA-3609 + TTTTCATCTCGATTGGTGAA 20 3595

BCLllA-3610 - TTTTTATCGAGCACAAA 17 3596

BCLllA-3611 + TTTTTCATCTCGATTGGTGA 20 3597

BCLllA-3612 + TTTTTTCATCTCGATTG 17 3598

BCLllA-3613 + TTTTTTC ATCTCG ATTG GTG 20 3599

Table 4E provides exemplary targeting domains for knocking out the BCL11A gene by targeting the early coding sequence the BCL11A gene selected according to fifth tier parameters. The targeting domains target outside the first 500bp of coding sequence downstream of 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 generates a double strand break (Cas9 nuclease) or a single- strand break (Cas9 nickase). In an embodiment, dual targeting is used to create two double strand breaks to remove the enhancer region in the BCL11A gene, e.g., the first gRNA is used to target upstream (i.e., 5') of the enhancer region in the BCL11A gene and the second gRNA is used to target downstream (i.e., 3') of the enhancer region in the BCL11A gene.

Table 4E 5th Tier

DNA Target Site SEQ ID gRNA Name Targeting Domain

Strand Length NO

BCLllA-3614 + TCGTCGGACTTGACCGTCAT 20 3600

BCLllA-3615 + GTCGTCGGACTTGACCGTCA 20 3601

BCLllA-3616 + CGTCGTCGGACTTGACCGTC 20 3602

BCLllA-3617 + CGTCGGACTTGACCGTCATG 20 3603

BCLllA-3618 - CCCATATTAGTGGTCCGGGC 20 3604

BCLllA-3619 + GCGGTCCGACTCGCCGGCCA 20 3605

BCLllA-3620 + CTCCGAGGAGTGCTCCGACG 20 3606

BCLllA-3621 - CCCCCATTCGGCGTAGTACC 20 3607

BCLllA-3622 + TCTCCGAGGAGTGCTCCGAC 20 3608

BCLllA-3623 - CCCGCGGGTTGGTATCCCTT 20 3609

BCLllA-3624 + GCGAGTACACGTTCTCCGTG 20 3610

BCLllA-3625 - CCCATTCGGCGTAGTACCCA 20 3611

BCLllA-3626 + CTCCGTGTTGGGCATCGCGG 20 3612

BCLllA-3627 + CCGCGCTTATGCTTCTCGCC 20 3613

BCLllA-3628 - CG ACG AAG ACTCGGTGG CCG 20 3614

BCLllA-3629 - ACCCCCACCGCATAGAGCGC 20 3615

BCLllA-3630 + ACTACGCCGAATGGGGGTGT 20 3616

BCLllA-3631 + CCGGGCCCGGACCACTAATA 20 3617

BCLllA-3632 + CGCGTAGCCGGCGAGCCACT 20 3618

BCLllA-3633 - TCGGAGCACTCCTCGGAGAA 20 3619

BCLllA-3634 - CGGAGCACTCCTCGGAGAAC 20 3620

BCLllA-3635 + TCTCTGGGTACTACGCCGAA 20 3621

BCLllA-3636 + TGCCGCAGAACTCGCATGAC 20 3622

BCLllA-3637 + GATACCAACCCGCGGGGTCA 20 3623

BCLllA-3638 + GGATACCAACCCGCGGGGTC 20 3624

BCLllA-3639 + GGGATACCAACCCGCGGGGT 20 3625

BCLllA-3640 - CCCCCACCGCATAGAGCGCC 20 3626

BCLllA-3641 + GGTTGGGGTCGTTCTCGCTC 20 3627

BCLllA-3642 - GCACGCCCCATATTAGTGGT 20 3628

BCLllA-3643 - TAAGCGCATCAAGCTCGAGA 20 3629

BCLllA-3644 + GTTCTCCGAGGAGTGCTCCG 20 3630

BCLllA-3645 + TCTCG AG CTTGATG CG CTTA 20 3631

BCLllA-3646 - CT AAG CG CATC AAG CTCG AG 20 3632

BCLllA-3647 - GTCGGAGCACTCCTCGGAGA 20 3633

BCLllA-3648 - TGGCCGCGGCTGCTCCCCGG 20 3634

BCLllA-3649 - CCCCACCGCATAGAGCGCCT 20 3635

BCLllA-3650 + CCTGAAGGGATACCAACCCG 20 3636

BCLllA-3651 - GCGCTTCTCCACACCGCCCG 20 3637

BCLllA-3652 - GCGCCCTGCCCGACGTCATG 20 3638 BCLllA-3653 - AACCCGGCACCAGCGACTTG 20 3639

BCLllA-3654 + CTCTGGGTACTACGCCGAAT 20 3640

BCLllA-3655 + CCCGTTCTCCGGGATCAGGT 20 3641

BCLllA-3656 - GAACGACCCCAACCTGATCC 20 3642

BCLllA-3657 + ACGCCGAATGGGGGTGTGTG 20 3643

BCLllA-3658 + GTCGCTGGTGCCGGGTTCCG 20 3644

BCLllA-3659 - CCCCGGGCGAGTCGGCCTCG 20 3645

BCLllA-3660 + CG GTG CACCACCAG GTTG CT 20 3646

BCLllA-3661 - GTCCACCACCGAGACATCAC 20 3647

BCLllA-3662 - TTAATGGCCGCGGCTGCTCC 20 3648

BCLllA-3663 + CTCTCTGGGTACTACGCCGA 20 3649

BCLllA-3664 + GCGCAAACTCCCGTTCTCCG 20 3650

BCLllA-3665 + CCCGGGCCCGGACCACTAAT 20 3651

BCLllA-3666 + GCCCCCAGGCGCTCTATGCG 20 3652

BCLllA-3667 - ATCGCCTTTTGCCTCCTCGT 20 3653

BCLllA-3668 - CCTCGTCGGAGCACTCCTCG 20 3654

BCLllA-3669 + GAGCTTGATGCGCTTAGAGA 20 3655

BCLllA-3670 + CCCCGTTCTCCGGGATCAGG 20 3656

BCLllA-3671 - CGGCCGCGATGCCCAACACG 20 3657

BCLllA-3672 + GCCCCCCGAGGCCGACTCGC 20 3658

BCLllA-3673 - CCCGGCCGCGATGCCCAACA 20 3659

BCLllA-3674 - CTCCTCGTCGGAGCACTCCT 20 3660

BCLllA-3675 + GTCTCGGTGGTGGACTAAAC 20 3661

BCLllA-3676 + CCCCAGGCGCTCTATGCGGT 20 3662

BCLllA-3677 + GGTCGCACAGGTTGCACTTG 20 3663

BCLllA-3678 + AGTCGCTGGTGCCGGGTTCC 20 3664

BCLllA-3679 - CCCGGTCAAGTCCAAGTCAT 20 3665

BCLllA-3680 - AGAACGACCCCAACCTGATC 20 3666

BCLllA-3681 + TCCGTGTTG GG CATCG CG G C 20 3667

BCLllA-3682 - CCTCCTCGTCGGAGCACTCC 20 3668

BCLllA-3683 - TCACTTGGACCCCCACCGCA 20 3669

BCLllA-3684 - CCCAACCTGATCCCGGAGAA 20 3670

BCLllA-3685 - ACTACGGCTTCGGGCTGAGC 20 3671

BCLllA-3686 - TTTG CG CTTCTCCAC ACCG C 20 3672

BCLllA-3687 + AAGTCGCTGGTGCCGGGTTC 20 3673

BCLllA-3688 - CCCCAACCTGATCCCGGAGA 20 3674

BCLllA-3689 - AAGACTCGGTGGCCGGCGAG 20 3675

BCLllA-3690 - GCGCGGCCACCTGGCCGAGG 20 3676

BCLllA-3691 - AATCGCCTTTTGCCTCCTCG 20 3677

BCLllA-3692 - ACGACCCCAACCTGATCCCG 20 3678

BCLllA-3693 - GATCCCGGAGAACGGGGACG 20 3679

BCLllA-3694 + GGGGCAGGTCGAACTCCTTC 20 3680 BCLllA-3695 - TGGCTATGGAGCCTCCCGCC 20 3681

BCLllA-3696 + CCCCCAGGCGCTCTATGCGG 20 3682

BCLllA-3697 - GCGGTTGAATCCAATGGCTA 20 3683

BCLllA-3698 - CTACGGCTTCGGGCTGAGCC 20 3684

BCLllA-3699 - ACAGCTCGCGGGGCGCGGTC 20 3685

BCLllA-3700 - CCCCCCTGTTTAGTCCACCA 20 3686

BCLllA-3701 + CGCATGACTTGGACTTGACC 20 3687

BCLllA-3702 - CACGGAAGTCCCCTGACCCC 20 3688

BCLllA-3703 - CCTCCCGCCATGGATTTCTC 20 3689

BCLllA-3704 + TCTCGGTGGTGGACTAAACA 20 3690

BCLllA-3705 + TGAACTTGGCCACCACGGAC 20 3691

BCLllA-3706 - CTTCTCTAAG CG C ATC AAG C 20 3692

BCLllA-3707 + AG CG CAAACTCCCGTTCTCC 20 3693

BCLllA-3708 + TCGGTGGTGGACTAAACAGG 20 3694

BCLllA-3709 - CG CCACCACG AG AACAG CTC 20 3695

BCLllA-3710 - CTCCCGCCATGGATTTCTCT 20 3696

BCLllA-3711 + CGAGCTTGATGCGCTTAGAG 20 3697

BCLllA-3712 + ATGCCCTG CATG ACGTCG G G 20 3698

BCLllA-3713 - TCTCT AAG CG CATC AAG CTC 20 3699

BCLllA-3714 + GTCC AAGTG ATGTCTCG GTG 20 3700

BCLllA-3715 + CCCCCGAGGCCGACTCGCCC 20 3701

BCLllA-3716 + CCCCGAGGCCGACTCGCCCG 20 3702

BCLllA-3717 + GAAATTTGAACGTCTTGCCG 20 3703

BCLllA-3718 + GTCGCTG CGTCTG CCCTCTT 20 3704

BCLllA-3719 - TGGAGGCGGCGCGCCACCAC 20 3705

BCLllA-3720 + CTTCTCG AG CTTGATG CG CT 20 3706

BCLllA-3721 + GAAGCGCAAACTCCCGTTCT 20 3707

BCLllA-3722 - GAGAGAGGCTTCCGGCCTGG 20 3708

BCLllA-3723 - TCCCCGGGCGAGTCGGCCTC 20 3709

BCLllA-3724 + CAAGTCG CTGGTG CCGGGTT 20 3710

BCLllA-3725 - CATAGAGCGCCTGGGGGCGG 20 3711

BCLllA-3726 + CTCGGTGGTGGACTAAACAG 20 3712

BCLllA-3727 + CCCCCCGAGGCCGACTCGCC 20 3713

BCLllA-3728 - GGTTTCTCTTG C AACACG C A 20 3714

BCLllA-3729 + ACTTGGACTTGACCGGGGGC 20 3715

BCLllA-3730 - TGATCCCGGAGAACGGGGAC 20 3716

BCLllA-3731 + TGTCTGGAGTCTCCGAAGCT 20 3717

BCLllA-3732 - ATG G ATTTCTCTAG G AG ACT 20 3718

BCLllA-3733 - TG CG GTTG A ATC C A ATG G CT 20 3719

BCLllA-3734 - CTCCCCGGGCGAGTCGGCCT 20 3720

BCLllA-3735 - CCTGATCCCGGAGAACGGGG 20 3721

BCLllA-3736 + TGTCTCG GTGGTG G ACTAAA 20 3722 BCLllA-3737 + CGGTGGTGGACTAAACAGGG 20 3723

BCLllA-3738 + TGCCCACCAAGTCGCTGGTG 20 3724

BCLllA-3739 - CGTGGTGGCCAAGTTCAAGA 20 3725

BCLllA-3740 - CATCACCCGAGTGCCTTTGA 20 3726

BCLllA-3741 - G CG G C AAG ACGTTC AAATTT 20 3727

BCLllA-3742 + AAGGGCTCTCGAGCTTCCAT 20 3728

BCLllA-3743 + GTCTGGAGTCTCCGAAGCTA 20 3729

BCLllA-3744 - CCCCGGCCGCGATGCCCAAC 20 3730

BCLllA-3745 + CTGTCAAAGGCACTCGGGTG 20 3731

BCLllA-3746 + CTTGGACTTGACCGGGGGCT 20 3732

BCLllA-3747 + GACTTGGACTTGACCGGGGG 20 3733

BCLllA-3748 + TG CGTCTG CCCTCTTTTG AG 20 3734

BCLllA-3749 + GGAGGCAAAAGGCGATTGTC 20 3735

BCLllA-3750 - GCAACACGCACAGAACACTC 20 3736

BCLllA-3751 + GCAGTAACCTTTGCATAGGG 20 3737

BCLllA-3752 - TGGTGCACCGGCGCAGCCAC 20 3738

BCLllA-3753 - TGGTGGCCAAGTTCAAGAGC 20 3739

BCLllA-3754 - GCATAAGCGCGGCCACCTGG 20 3740

BCLllA-3755 + TTGCATAGGGCTGGGCCGGC 20 3741

BCLllA-3756 - CCAACCTGATCCCGGAGAAC 20 3742

BCLllA-3757 - AG ATGTGTG G CAGTTTTCG G 20 3743

BCLllA-3758 - CAGTTTTCGGATGGAAGCTC 20 3744

BCLllA-3759 - GCTCCCCGGGCGAGTCGGCC 20 3745

BCLllA-3760 - GGGTGGACTACGGCTTCGGG 20 3746

BCLllA-3761 - TATCCCTTCAG G ACTAG GTG 20 3747

BCLllA-3762 - ATCTCGGGGCGCAGCGGCAC 20 3748

BCLllA-3763 + CGCTCTTGAACTTGGCCACC 20 3749

BCLllA-3764 - GCACCGGCGCAGCCACACGG 20 3750

BCLllA-3765 + GCTTCTCGCCCAGGACCTGG 20 3751

BCLllA-3766 - TCCCGGAGAACGGGGACGAG 20 3752

BCLllA-3767 + CAGCACCCTGTCAAAGGCAC 20 3753

BCLllA-3768 + CATTCTGCACCTAGTCCTGA 20 3754

BCLllA-3769 - CTTTAACCTGCTAAGAATAC 20 3755

BCLllA-3770 - GTCTCTCCACCGCCAGCTCC 20 3756

BCLllA-3771 - TCTCTCCACCGCCAGCTCCC 20 3757

BCLllA-3772 + TGCTTCTCGCCCAGGACCTG 20 3758

BCLllA-3773 + GCGCCGCCTCCAGGCTCAGC 20 3759

BCLllA-3774 + AGATCCCTCCGTCCAGCTCC 20 3760

BCLllA-3775 - CGAGAGGGTGGACTACGGCT 20 3761

BCLllA-3776 + CGTCCAGCTCCCCGGGCGGT 20 3762

BCLllA-3777 + CCAGCTCTCTAAGTCTCCTA 20 3763

BCLllA-3778 + TCGCATGACTTGGACTTGAC 20 3764 BCLllA-3779 + GCACCATGCCCTGCATGACG 20 3765

BCLllA-3780 + AAGGCGATTGTCTGGAGTCT 20 3766

BCLllA-3781 + GCCTGGAGGCCGCGTAGCCG 20 3767

BCLllA-3782 - GCGGCCACCTGGCCGAGGCC 20 3768

BCLllA-3783 - AGAATACCAGGATCAGTATC 20 3769

BCLllA-3784 - GATGTGTGGCAGTTTTCGGA 20 3770

BCLllA-3785 - TCTCCACACCGCCCGGGGAG 20 3771

BCLllA-3786 - CCTGGAGGCGGCGCGCCACC 20 3772

BCLllA-3787 + CTGGTATTCTTAGCAGGTTA 20 3773

BCLllA-3788 + TAGAGAAGGGGCTCAGCGAG 20 3774

BCLllA-3789 + G AGTGTTCTGTG CGTGTTG C 20 3775

BCLllA-3790 - AATAACCCCTTTAACCTGCT 20 3776

BCLllA-3791 + A AAG CG CCCTTCTG CC AG G C 20 3777

BCLllA-3792 + GTCCAGCTCCCCGGGCGGTG 20 3778

BCLllA-3793 + AAGGGCGGCTTGCTACCTGG 20 3779

BCLllA-3794 + G A AAG CG CCCTTCTG CC AG G 20 3780

BCLllA-3795 + AGGGCGGCTTGCTACCTGGC 20 3781

BCLllA-3796 - CGCGGGGCGCGGTCGTGGGC 20 3782

BCLllA-3797 - GCGAGGCCTTCCACCAGGTC 20 3783

BCLllA-3798 + ACTTCCCGTGCCGCTGCGCC 20 3784

BCLllA-3799 - GCACAGAACACTCATGGATT 20 3785

BCLllA-3800 + CCAGCTCCCCGGGCGGTGTG 20 3786

BCLllA-3801 - ACCGCCCGGGGAGCTGGACG 20 3787

BCLllA-3802 + TG GTTG CAGTAACCTTTG CA 20 3788

BCLllA-3803 - AGGAGACTTAGAGAGCTGGC 20 3789

BCLllA-3804 - ACCGGCGCAGCCACACGGGC 20 3790

BCLllA-3805 + ACATTCTGCACCTAGTCCTG 20 3791

BCLllA-3806 + GTGTTCTGTG CGTGTTG CAA 20 3792

BCLllA-3807 - TGGCCCTGGCCACCCATCAC 20 3793

BCLllA-3808 + TGCATAGGGCTGGGCCGGCC 20 3794

BCLllA-3809 - AATACCAGGATCAGTATCGA 20 3795

BCLllA-3810 + TCCTGAAGGGATACCAACCC 20 3796

BCLllA-3811 + CTCCTAGAGAAATCCATGGC 20 3797

BCLllA-3812 + TGGCGGTGGAGAGACCGTCG 20 3798

BCLllA-3813 - GGA I 1 I C I C I AGGAGAC I I A 20 3799

BCLllA-3814 + CTCGCATGACTTGGACTTGA 20 3800

BCLllA-3815 - GATCTCGGGGCGCAGCGGCA 20 3801

BCLllA-3816 + GGTGGTGGACTAAACAGGGG 20 3802

BCLllA-3817 + AGGCCTCG CTGAAGTG CTG C 20 3803

BCLllA-3818 + CCACCAGGTTGCTCTGAAAT 20 3804

BCLllA-3819 - ACCGCATAGAGCGCCTGGGG 20 3805

BCLllA-3820 - CCAGCAAGCTGAAGCGCCAC 20 3806 BCLllA-3821 + GGCCTCG CTGAAGTG CTG CA 20 3807

BCLllA-3822 - CGTGCACCCAGGCCAGCAAG 20 3808

BCLllA-3823 + GGCGGGAGGCTCCATAGCCA 20 3809

BCLllA-3824 + AGGAGGCAAAAGGCGATTGT 20 3810

BCLllA-3825 - A A AG ATC CCTTC CTTAG CTT 20 3811

BCLllA-3826 + GGAGTCTCCGAAGCTAAGGA 20 3812

BCLllA-3827 + G CG CTTAG AGAAGGGGCTCA 20 3813

BCLllA-3828 + CAGCTTTTTGGACAGGCCCC 20 3814

BCLllA-3829 + GCACTCGGGTGATGGGTGGC 20 3815

BCLllA-3830 + CACGCCCACGACCGCGCCCC 20 3816

BCLllA-3831 + AAGTTGTACATGTGTAGCTG 20 3817

BCLllA-3832 - AGTCCGTGGTGGCCAAGTTC 20 3818

BCLllA-3833 - CCCGGAGAACGGGGACGAGG 20 3819

BCLllA-3834 - CGGGCAGGCCCAG CTC A A A A 20 3820

BCLllA-3835 + TGGTATTCTTAGCAGGTTAA 20 3821

BCLllA-3836 + TTGTCTGCAATATGAATCCC 20 3822

BCLllA-3837 + GTCTCCTAGAGAAATCCATG 20 3823

BCLllA-3838 + TGGACTTGACCGGGGGCTGG 20 3824

BCLllA-3839 + TGGAGTCTCCGAAGCTAAGG 20 3825

BCLllA-3840 + TGAGCTGGGCCTGCCCGGGC 20 3826

BCLllA-3841 - CAAAGATCCCTTCCTTAGCT 20 3827

BCLllA-3842 + TGCCACACATCTTGAGCTCT 20 3828

BCLllA-3843 - CCGCCCGGGGAGCTGGACGG 20 3829

BCLllA-3844 + AGAGAAGGGGCTCAGCGAGC 20 3830

BCLllA-3845 - GGAGACTTAGAGAGCTGGCA 20 3831

BCLllA-3846 + GAATCCCATGGAGAGGTGGC 20 3832

BCLllA-3847 + CG CTGAAGTG CTG C ATG G AG 20 3833

BCLllA-3848 + AGGACATTCTGCACCTAGTC 20 3834

BCLllA-3849 + AATCCCATGGAGAGGTGGCT 20 3835

BCLllA-3850 + TGAGCTCTCTGGGTACTACG 20 3836

BCLllA-3851 - GGGCCACAGGGACACTTGCG 20 3837

BCLllA-3852 - TAGGAGACTTAGAGAGCTGG 20 3838

BCLllA-3853 - CCTTTGACAGGGTGCTGCGG 20 3839

BCLllA-3854 - TGGCCGAGGCCGAGGGCCAC 20 3840

BCLllA-3855 + GGAAGGGATCTTTGAGCTGC 20 3841

BCLllA-3856 + TCTAAGTAGATTCTTAATCC 20 3842

BCLllA-3857 - GGGGCGCAGCGGCACGGGAA 20 3843

BCLllA-3858 - CTGGCCGAGGCCGAGGGCCA 20 3844

BCLllA-3859 - CTCAAG ATGTGTGG CAGTTT 20 3845

BCLllA-3860 + CGAAGCTAAGGAAGGGATCT 20 3846

BCLllA-3861 + TGCCAGCTCTCTAAGTCTCC 20 3847

BCLllA-3862 + TCTCCTAGAGAAATCCATGG 20 3848 BCLllA-3863 - GCCACCACGAGAACAGCTCG 20 3849

BCLllA-3864 + TCTG C A AT ATG A ATC CC ATG 20 3850

BCLllA-3865 - CAG CTCC ATG CAG CACTTC A 20 3851

BCLllA-3866 - G CCTGTCC AAAAAG CTG CTG 20 3852

BCLllA-3867 - TAAGAATACCAGGATCAGTA 20 3853

BCLllA-3868 - GGATCTCGGGGCGCAGCGGC 20 3854

BCLllA-3869 - GGCA I 1 1 I CGGA I GAAGC 20 3855

BCLllA-3870 - CGGTCGTGGGCGTGGGCGAC 20 3856

BCLllA-3871 + GCATCGCGGCCGGGGGCAGG 20 3857

BCLllA-3872 - AATCTACTTAGAAAGCGAAC 20 3858

BCLllA-3873 + A AG G G GTTATTGTCTG CAAT 20 3859

BCLllA-3874 + GGACTTGACCGGGGGCTGGG 20 3860

BCLllA-3875 - TCATGGATTAAGAATCTACT 20 3861

BCLllA-3876 - AGAGGCTTCCGGCCTGGCAG 20 3862

BCLllA-3877 - GGCCTTCCACCAGGTCCTGG 20 3863

BCLllA-3878 + TG G CG CTTC AG CTTG CTG G C 20 3864

BCLllA-3879 - C CG CAT AG AG CGCCTGGGGG 20 3865

BCLllA-3880 + GGACCTGGTGGAAGGCCTCG 20 3866

BCLllA-3881 - CCTTCCACCAGGTCCTGGGC 20 3867

BCLllA-3882 + TGTCTGCAATATGAATCCCA 20 3868

BCLllA-3883 - GGAGCTGGACGGAGGGATCT 20 3869

BCLllA-3884 + GACTTGACCGGGGGCTGGGA 20 3870

BCLllA-3885 - TCCTTCCCAGCCACCTCTCC 20 3871

BCLllA-3886 + CTCTTTTGAGCTGGGCCTGC 20 3872

BCLllA-3887 - TGCGCTTCTCCACACCGCCC 20 3873

BCLllA-3888 + G CA AG AG AAACC ATG CACTG 20 3874

BCLllA-3889 - GGGAGCTGGACGGAGGGATC 20 3875

BCLllA-3890 + GTTCCGGGGAGCTGGCGGTG 20 3876

BCLllA-3891 + TGAATCCCATGGAGAGGTGG 20 3877

BCLllA-3892 + CGGGTTCCGGGGAGCTGGCG 20 3878

BCLllA-3893 + GTGGACTAAACAGGGGGGGA 20 3879

BCLllA-3894 + GGCTGCCCAGCAGCAG CTTT 20 3880

BCLllA-3895 + GAAGGGATCTTTGAGCTGCC 20 3881

BCLllA-3896 - CCTTCCCAGCCACCTCTCCA 20 3882

BCLllA-3897 - GCGCAGCGGCACGGGAAGTG 20 3883

BCLllA-3898 + GGGTTCCGGGGAGCTGGCGG 20 3884

BCLllA-3899 + TCCTCCTCGTCCCCGTTCTC 20 3885

BCLllA-3900 - GCAGCGGCACGGGAAGTGGA 20 3886

BCLllA-3901 - TGCTGGGCAGCCCCAGCTCG 20 3887

BCLllA-3902 - GGGCGCAGCGGCACGGGAAG 20 3888

BCLllA-3903 - ACACCGCCCGGGGAGCTGGA 20 3889

BCLllA-3904 + CCCATGGAGAGGTGGCTGGG 20 3890 BCLllA-3905 + TTCCTCCTCGTCCCCGTTCT 20 3891

BCLllA-3906 - ATCT ACTTAG A A AG CG A AC A 20 3892

BCLllA-3907 - CCCGGGCAGGCCCAGCTCAA 20 3893

BCLllA-3908 - CACACCGCCCGGGGAGCTGG 20 3894

BCLllA-3909 + ACTAAACAGGGGGGGAGTGG 20 3895

BCLllA-3910 + GACCGGGGGCTGGGAGGGAG 20 3896

BCLllA-3911 + GGGCCGGCCTGGGGACAGCG 20 3897

BCLllA-3912 + GCATAGGGCTGGGCCGGCCT 20 3898

BCLllA-3913 - ATTAAGAATCTACTTAGAAA 20 3899

BCLllA-3914 + CTAAACAGGGGGGGAGTGGG 20 3900

BCLllA-3915 + TTGACCGGGGGCTGGGAGGG 20 3901

BCLllA-3916 - CGCGGTCGTGGGCGTGGGCG 20 3902

BCLllA-3917 + GAGGGAGGGGGGGCGTCGCC 20 3903

BCLllA-3918 - GGAGAACGGGGACGAGGAGG 20 3904

BCLllA-3919 + CTTGACCGGGGGCTGGGAGG 20 3905

BCLllA-3920 + GGAGGGAGGGGGGGCGTCGC 20 3906

BCLllA-3921 + ACCGGGGGCTGGGAGGGAGG 20 3907

BCLllA-3922 - CGCAGCGGCACGGGAAGTGG 20 3908

BCLllA-3923 + GCGGATTGCAGAGGAGGGAG 20 3909

BCLllA-3924 + GGAGGGGGGGCGTCGCCAGG 20 3910

BCLllA-3925 + GGCGGATTGCAGAGGAGGGA 20 3911

BCLllA-3926 + GAGGGGCGGATTGCAGAGGA 20 3912

BCLllA-3927 + GGGGCGGATTGCAGAGGAGG 20 3913

BCLllA-3928 - GAGGAGCTGACGGAGAGCGA 20 3914

BCLllA-3929 + TCCGAAAACTGCCACACATC 20 3915

BCLllA-3930 + CGGATTGCAGAGGAGGGAGG 20 3916

BCLllA-3931 + GGAGGGGCGGATTGCAGAGG 20 3917

BCLllA-3932 + GGGCGGATTGCAGAGGAGGG 20 3918

BCLllA-3933 + AGGAGGGGCGGATTGCAGAG 20 3919

BCLllA-3934 - AGAACGGGGACGAGGAGGAA 20 3920

BCLllA-3935 + GAGGGAGGAGGGGCGGATTG 20 3921

BCLllA-3936 - TTG CG CTTCTCCAC ACCG CC 20 3922

BCLllA-3937 - AGCTGACGGAGAGCGAGAGG 20 3923

BCLllA-3938 - AGGAGGAGCTGACGGAGAGC 20 3924

BCLllA-3939 + GGGGCTGGGAGGGAGGAGGG 20 3925

BCLllA-3940 + GGGAGGAGGGGCGGATTGCA 20 3926

BCLllA-3941 + CCGTGTTGGGCATCGCGGCC 20 3927

BCLllA-3942 - GAACGGGGACGAGGAGGAAG 20 3928

BCLllA-3943 + GGAGGAGGGGCGGATTGCAG 20 3929

BCLllA-3944 - GGAGGAGGAGCTGACGGAGA 20 3930

BCLllA-3945 - ACGGGGACGAGGAGGAAGAG 20 3931

BCLllA-3946 - AGGAGGAGGAGGAGCTGACG 20 3932 BCLllA-3947 - ACGACGAGGAAGAGGAAGAA 20 3933

BCLllA-3948 - ACGAGGAAGAGGAAGAAGAG 20 3934

BCLllA-3949 - AGGAGGAAGAGGAGGACGAC 20 3935

BCLllA-3950 - AAGAGGAGGACGACGAGGAA 20 3936

BCLllA-3951 - AGAGGAGGAGGAGGAGCTGA 20 3937

BCLllA-3952 - GGAGGAAGAGGAGGACGACG 20 3938

BCLllA-3953 - CGAGGAGGAAGAGGAGGACG 20 3939

BCLllA-3954 - CGAGGAAGAGGAAGAAGAGG 20 3940

BCLllA-3955 - AAGAGGAGGAGGAGGAGCTG 20 3941

BCLllA-3956 - CGACGAGGAAGAGGAAGAAG 20 3942

BCLllA-3957 - GGAGGACGACGAGGAAGAGG 20 3943

BCLllA-3958 - AGAGGAGGACGACGAGGAAG 20 3944

BCLllA-3959 - GGACGACGAGGAAGAGGAAG 20 3945

BCLllA-3960 - GGAAGAGGAGGACGACGAGG 20 3946

BCLllA-3961 - AGGAAGAAGAGGAGGAAGAG 20 3947

BCLllA-3962 - AAGAGGAAGAAGAGGAGGAA 20 3948

BCLllA-3963 - GGAAGAGGAAGAAGAGGAGG 20 3949

BCLllA-3964 - AAGAAGAGGAGGAAGAGGAG 20 3950

BCLllA-3965 - AAGAGGAGGAAGAGGAGGAG 20 3951

BCLllA-3966 - AGAGGAAGAAGAGGAGGAAG 20 3952

BCLllA-3967 - GGAAGAAGAGGAGGAAGAGG 20 3953

BCLllA-3968 - AGAAGAGGAGGAAGAGGAGG 20 3954

BCLllA-3969 - AGAGGAGGAAGAGGAGGAGG 20 3955

BCLllA-3970 + TCGGACTTGACCGTCAT 17 3956

BCLllA-3971 + GTCGGACTTGACCGTCA 17 3957

BCLllA-3972 + CGTCGGACTTGACCGTC 17 3958

BCLllA-3973 + CGGACTTGACCGTCATG 17 3959

BCLllA-3974 - ATATTAGTGGTCCGGGC 17 3960

BCLllA-3975 + GTCCGACTCGCCGGCCA 17 3961

BCLllA-3976 + CGAGGAGTGCTCCGACG 17 3962

BCLllA-3977 - CCATTCGGCGTAGTACC 17 3963

BCLllA-3978 + CCGAGGAGTGCTCCGAC 17 3964

BCLllA-3979 - GCGGGTTGGTATCCCTT 17 3965

BCLllA-3980 + AGTACACGTTCTCCGTG 17 3966

BCLllA-3981 - ATTCGGCGTAGTACCCA 17 3967

BCLllA-3982 + CGTGTTG GG CATCG CG G 17 3968

BCLllA-3983 + CG CTTATG CTTCTCG CC 17 3969

BCLllA-3984 - CGAAGACTCGGTGGCCG 17 3970

BCLllA-3985 - CCC ACCG CATAG AG CG C 17 3971

BCLllA-3986 + ACGCCGAATGGGGGTGT 17 3972

BCLllA-3987 + GGCCCGGACCACTAATA 17 3973

BCLllA-3988 + GTAGCCGGCGAGCCACT 17 3974 BCLllA-3989 - GAGCACTCCTCGGAGAA 17 3975

BCLllA-3990 - AGCACTCCTCGGAGAAC 17 3976

BCLllA-3991 + CTGGGTACTACGCCGAA 17 3977

BCLllA-3992 + CGCAGAACTCGCATGAC 17 3978

BCLllA-3993 + ACCAACCCGCGGGGTCA 17 3979

BCLllA-3994 + TACCAACCCGCGGGGTC 17 3980

BCLllA-3995 + ATACCAACCCGCGGGGT 17 3981

BCLllA-3996 - CCACCGCATAGAGCGCC 17 3982

BCLllA-3997 + TGGGGTCGTTCTCGCTC 17 3983

BCLllA-3998 - CGCCCCATATTAGTGGT 17 3984

BCLllA-3999 - GCGCATCAAGCTCGAGA 17 3985

BCLllA-4000 + CTCCGAGGAGTGCTCCG 17 3986

BCLllA-4001 + CG AG CTTG ATG CG CTTA 17 3987

BCLllA-4002 - AG CG CATCAAG CTCG AG 17 3988

BCLllA-4003 - GGAGCACTCCTCGGAGA 17 3989

BCLllA-4004 - CCGCGGCTGCTCCCCGG 17 3990

BCLllA-4005 - C ACCG C ATAG AG CG CCT 17 3991

BCLllA-4006 + GAAGGGATACCAACCCG 17 3992

BCLllA-4007 - CTTCTCCACACCGCCCG 17 3993

BCLllA-4008 - CCCTGCCCGACGTCATG 17 3994

BCLllA-4009 - CCGGCACCAGCGACTTG 17 3995

BCLllA-4010 + TGGGTACTACGCCGAAT 17 3996

BCLllA-4011 + GTTCTCCGGGATCAGGT 17 3997

BCLllA-4012 - CGACCCCAACCTGATCC 17 3998

BCLllA-4013 + CCGAATGGGGGTGTGTG 17 3999

BCLllA-4014 + GCTGGTGCCGGGTTCCG 17 4000

BCLllA-4015 - CGGGCGAGTCGGCCTCG 17 4001

BCLllA-4016 + TGCACCACCAGGTTGCT 17 4002

BCLllA-4017 - CACCACCGAGACATCAC 17 4003

BCLllA-4018 - ATGGCCGCGGCTGCTCC 17 4004

BCLllA-4019 + TCTGGGTACTACGCCGA 17 4005

BCLllA-4020 + CAAACTCCCGTTCTCCG 17 4006

BCLllA-4021 + GGGCCCGGACCACTAAT 17 4007

BCLllA-4022 + CCCAGGCGCTCTATGCG 17 4008

BCLllA-4023 - GCCTTTTGCCTCCTCGT 17 4009

BCLllA-4024 - CGTCGGAGCACTCCTCG 17 4010

BCLllA-4025 + CTTGATGCGCTTAGAGA 17 4011

BCLllA-4026 + CGTTCTCCGGGATCAGG 17 4012

BCLllA-4027 - CCGCGATGCCCAACACG 17 4013

BCLllA-4028 + CCCCGAGGCCGACTCGC 17 4014

BCLllA-4029 - GGCCGCGATGCCCAACA 17 4015

BCLllA-4030 - CTCGTCGGAGCACTCCT 17 4016 BCLllA-4031 + TCGGTGGTGGACTAAAC 17 4017

BCLllA-4032 + CAG G CG CTCTATG CGGT 17 4018

BCLllA-4033 + CG C ACAG GTTG CACTTG 17 4019

BCLllA-4034 + CGCTGGTGCCGGGTTCC 17 4020

BCLllA-4035 - GGTCAAGTCCAAGTCAT 17 4021

BCLllA-4036 - ACGACCCCAACCTGATC 17 4022

BCLllA-4037 + GTGTTGGGCATCGCGGC 17 4023

BCLllA-4038 - CCTCGTCGGAGCACTCC 17 4024

BCLllA-4039 - CTTGGACCCCCACCGCA 17 4025

BCLllA-4040 - AACCTGATCCCGGAGAA 17 4026

BCLllA-4041 - ACGGCTTCGGGCTGAGC 17 4027

BCLllA-4042 - GCGCTTCTCCACACCGC 17 4028

BCLllA-4043 + TCGCTGGTGCCGGGTTC 17 4029

BCLllA-4044 - CAACCTGATCCCGGAGA 17 4030

BCLllA-4045 - ACTCGGTGGCCGGCGAG 17 4031

BCLllA-4046 - CGGCCACCTGGCCGAGG 17 4032

BCLllA-4047 - CGCCTTTTGCCTCCTCG 17 4033

BCLllA-4048 - ACCCCAACCTGATCCCG 17 4034

BCLllA-4049 - CCCGGAGAACGGGGACG 17 4035

BCLllA-4050 + G CAG GTCG A ACTCCTTC 17 4036

BCLllA-4051 - CTATG G AG CCTCCCG CC 17 4037

BCLllA-4052 + CC AGG CG CTCTATG CG G 17 4038

BCLllA-4053 - GTTG A ATC C A ATG G CT A 17 4039

BCLllA-4054 - CGGCTTCGGGCTGAGCC 17 4040

BCLllA-4055 - GCTCGCGGGGCGCGGTC 17 4041

BCLllA-4056 - CCCTGTTTAGTCCACCA 17 4042

BCLllA-4057 + ATGACTTGGACTTGACC 17 4043

BCLllA-4058 - GGAAGTCCCCTGACCCC 17 4044

BCLllA-4059 - CCCGCCATGGATTTCTC 17 4045

BCLllA-4060 + CGGTGGTGGACTAAACA 17 4046

BCLllA-4061 + ACTTGGCCACCACGGAC 17 4047

BCLllA-4062 - CTCTAAG CG C ATC AAG C 17 4048

BCLllA-4063 + GCAAACTCCCGTTCTCC 17 4049

BCLllA-4064 + GTGGTG G ACTAA ACAG G 17 4050

BCLllA-4065 - CACCACGAGAACAGCTC 17 4051

BCLllA-4066 - CCGCCATGGATTTCTCT 17 4052

BCLllA-4067 + G CTTG ATG CG CTTAG AG 17 4053

BCLllA-4068 + CCCTGCATGACGTCGGG 17 4054

BCLllA-4069 - CT AAG CG CATC AAG CTC 17 4055

BCLllA-4070 + CAAGTGATGTCTCGGTG 17 4056

BCLllA-4071 + CCGAGGCCGACTCGCCC 17 4057

BCLllA-4072 + CGAGGCCGACTCGCCCG 17 4058 BCLllA-4073 + ATTTGAACGTCTTGCCG 17 4059

BCLllA-4074 + GCTGCGTCTGCCCTCTT 17 4060

BCLllA-4075 - AGGCGGCGCGCCACCAC 17 4061

BCLllA-4076 + CTCG AG CTTG ATG CG CT 17 4062

BCLllA-4077 + G CG CAA ACTCCCGTTCT 17 4063

BCLllA-4078 - AGAGGCTTCCGGCCTGG 17 4064

BCLllA-4079 - CCGGGCGAGTCGGCCTC 17 4065

BCLllA-4080 + GTCGCTGGTGCCGGGTT 17 4066

BCLllA-4081 - AGAGCGCCTGGGGGCGG 17 4067

BCLllA-4082 + GGTGGTGGACTAAACAG 17 4068

BCLllA-4083 + CCCGAGGCCGACTCGCC 17 4069

BCLllA-4084 - TTCTCTTG CAAC ACG CA 17 4070

BCLllA-4085 + TGGACTTGACCGGGGGC 17 4071

BCLllA-4086 - TCCCGGAGAACGGGGAC 17 4072

BCLllA-4087 + CTGGAGTCTCCGAAGCT 17 4073

BCLllA-4088 - GA I 1 I C I C I AGGAGAC I 17 4074

BCLllA-4089 - G GTTG A ATC C A ATG G CT 17 4075

BCLllA-4090 - CCCGGGCGAGTCGGCCT 17 4076

BCLllA-4091 - GATCCCGGAGAACGGGG 17 4077

BCLllA-4092 + CTCGGTGGTGGACTAAA 17 4078

BCLllA-4093 + TGGTGGACTAAACAGGG 17 4079

BCLllA-4094 + CCACCAAGTCGCTGGTG 17 4080

BCLllA-4095 - GGTGGCCAAGTTCAAGA 17 4081

BCLllA-4096 - CACCCGAGTGCCTTTGA 17 4082

BCLllA-4097 - GCAAGACGTTCAAATTT 17 4083

BCLllA-4098 + GGCTCTCGAGCTTCCAT 17 4084

BCLllA-4099 + TGGAGTCTCCGAAGCTA 17 4085

BCLllA-4100 - CGGCCGCGATGCCCAAC 17 4086

BCLllA-4101 + TCAAAGGCACTCGGGTG 17 4087

BCLllA-4102 + GGACTTGACCGGGGGCT 17 4088

BCLllA-4103 + TTGGACTTGACCGGGGG 17 4089

BCLllA-4104 + GTCTGCCCTCTTTTGAG 17 4090

BCLllA-4105 + G G CAAAAG G CG ATTGTC 17 4091

BCLllA-4106 - ACACGCACAGAACACTC 17 4092

BCLllA-4107 + GTAACCTTTGCATAGGG 17 4093

BCLllA-4108 - TGCACCGGCGCAGCCAC 17 4094

BCLllA-4109 - TGGCCAAGTTCAAGAGC 17 4095

BCLllA-4110 - TAAGCGCGGCCACCTGG 17 4096

BCLllA-4111 + CATAGGGCTGGGCCGGC 17 4097

BCLllA-4112 - ACCTGATCCCGGAGAAC 17 4098

BCLllA-4113 - TGTGTGGCAGTTTTCGG 17 4099

BCLllA-4114 - TTTTCGGATGGAAGCTC 17 4100 BCLllA-4115 - CCCCGGGCGAGTCGGCC 17 4101

BCLllA-4116 - TGGACTACGGCTTCGGG 17 4102

BCLllA-4117 - CCCTTCAGGACTAGGTG 17 4103

BCLllA-4118 - TCGGGGCGCAGCGGCAC 17 4104

BCLllA-4119 + TCTTGAACTTGGCCACC 17 4105

BCLllA-4120 - CCGGCGCAGCCACACGG 17 4106

BCLllA-4121 + TCTCGCCCAGGACCTGG 17 4107

BCLllA-4122 - CGGAGAACGGGGACGAG 17 4108

BCLllA-4123 + CACCCTGTCAAAGGCAC 17 4109

BCLllA-4124 + TCTGCACCTAGTCCTGA 17 4110

BCLllA-4125 - TAACCTG CTAAG AATAC 17 4111

BCLllA-4126 - TCTCCACCGCCAGCTCC 17 4112

BCLllA-4127 - CTCCACCGCCAGCTCCC 17 4113

BCLllA-4128 + TTCTCGCCCAGGACCTG 17 4114

BCLllA-4129 + CCGCCTCCAGGCTCAGC 17 4115

BCLllA-4130 + TCCCTCCGTCCAGCTCC 17 4116

BCLllA-4131 - GAGGGTGGACTACGGCT 17 4117

BCLllA-4132 + CCAGCTCCCCGGGCGGT 17 4118

BCLllA-4133 + GCTCTCTAAGTCTCCTA 17 4119

BCLllA-4134 + CATGACTTGGACTTGAC 17 4120

BCLllA-4135 + CCATGCCCTGCATGACG 17 4121

BCLllA-4136 + GCGATTGTCTGGAGTCT 17 4122

BCLllA-4137 + TGGAGGCCGCGTAGCCG 17 4123

BCLllA-4138 - GCCACCTGGCCGAGGCC 17 4124

BCLllA-4139 - ATACCAGGATCAGTATC 17 4125

BCLllA-4140 - GTGTGGCAGTTTTCGGA 17 4126

BCLllA-4141 - CCACACCGCCCGGGGAG 17 4127

BCLllA-4142 - GGAGGCGGCGCGCCACC 17 4128

BCLllA-4143 + GTATTCTTAG CAG GTTA 17 4129

BCLllA-4144 + AGAAGGGGCTCAGCGAG 17 4130

BCLllA-4145 + TGTTCTGTG CGTGTTG C 17 4131

BCLllA-4146 - AACCCCTTTAACCTGCT 17 4132

BCLllA-4147 + G CG CC CTTCTG C C AG G C 17 4133

BCLllA-4148 + CAGCTCCCCGGGCGGTG 17 4134

BCLllA-4149 + GGCGGCTTGCTACCTGG 17 4135

BCLllA-4150 + AGCGCCCTTCTGCCAGG 17 4136

BCLllA-4151 + GCGGCTTGCTACCTGGC 17 4137

BCLllA-4152 - GGGGCGCGGTCGTGGGC 17 4138

BCLllA-4153 - AGGCCTTCCACCAGGTC 17 4139

BCLllA-4154 + TCCCGTGCCGCTGCGCC 17 4140

BCLllA-4155 - CAGAACACTCATGGATT 17 4141

BCLllA-4156 + GCTCCCCGGGCGGTGTG 17 4142 BCLllA-4157 - GCCCGGGGAGCTGGACG 17 4143

BCLllA-4158 + TTGCAGTAACCTTTGCA 17 4144

BCLllA-4159 - AGACTTAGAGAGCTGGC 17 4145

BCLllA-4160 - GGCGCAGCCACACGGGC 17 4146

BCLllA-4161 + TTCTGCACCTAGTCCTG 17 4147

BCLllA-4162 + TTCTGTG CGTGTTG CAA 17 4148

BCLllA-4163 - CCCTGGCCACCCATCAC 17 4149

BCLllA-4164 + ATAGGGCTGGGCCGGCC 17 4150

BCLllA-4165 - ACCAGGATCAGTATCGA 17 4151

BCLllA-4166 + TGAAGGGATACCAACCC 17 4152

BCLllA-4167 + CTAG AG A A ATC C ATG G C 17 4153

BCLllA-4168 + CGGTGGAGAGACCGTCG 17 4154

BCLllA-4169 - TTTCTCTAGGAGACTTA 17 4155

BCLllA-4170 + GCATGACTTGGACTTGA 17 4156

BCLllA-4171 - CTCGGGGCGCAGCGGCA 17 4157

BCLllA-4172 + GGTGGACTAAACAGGGG 17 4158

BCLllA-4173 + CCTCG CTG AAGTG CTG C 17 4159

BCLllA-4174 + CCAGGTTGCTCTGAAAT 17 4160

BCLllA-4175 - G C ATAG AGCGCCTGGGG 17 4161

BCLllA-4176 - G CAAG CTG AAG CG CC AC 17 4162

BCLllA-4177 + CTCG CTG AAGTG CTG C A 17 4163

BCLllA-4178 - GCACCCAGGCCAGCAAG 17 4164

BCLllA-4179 + GGGAGGCTCCATAGCCA 17 4165

BCLllA-4180 + AGGCAAAAGGCGATTGT 17 4166

BCLllA-4181 - GATCCCTTCCTTAGCTT 17 4167

BCLllA-4182 + GTCTCCGAAGCTAAGGA 17 4168

BCLllA-4183 + CTTAGAGAAGGGGCTCA 17 4169

BCLllA-4184 + CTTTTTGGACAGGCCCC 17 4170

BCLllA-4185 + CTCGGGTGATGGGTGGC 17 4171

BCLllA-4186 + GCCCACGACCGCGCCCC 17 4172

BCLllA-4187 + TTGTACATGTGTAG CTG 17 4173

BCLllA-4188 - CCGTGGTGGCCAAGTTC 17 4174

BCLllA-4189 - GGAGAACGGGGACGAGG 17 4175

BCLllA-4190 - GCAGG CCCAG CTCAAAA 17 4176

BCLllA-4191 + TATTCTTAG CAG GTTAA 17 4177

BCLllA-4192 + TCTGCAATATGAATCCC 17 4178

BCLllA-4193 + TCCTAGAGAAATCCATG 17 4179

BCLllA-4194 + ACTTGACCGGGGGCTGG 17 4180

BCLllA-4195 + AGTCTCCGAAGCTAAGG 17 4181

BCLllA-4196 + GCTGGGCCTGCCCGGGC 17 4182

BCLllA-4197 - AG ATCC CTTC CTTAG CT 17 4183

BCLllA-4198 + CACACATCTTGAGCTCT 17 4184 BCLllA-4199 - CCCGGGGAGCTGGACGG 17 4185

BCLllA-4200 + GAAGGGGCTCAGCGAGC 17 4186

BCLllA-4201 - G ACTTAG AG AG CTG G C A 17 4187

BCLllA-4202 + TCCCATGGAGAGGTGGC 17 4188

BCLllA-4203 + TGAAGTG CTG C ATG G AG 17 4189

BCLllA-4204 + ACATTCTGCACCTAGTC 17 4190

BCLllA-4205 + CCCATGGAGAGGTGGCT 17 4191

BCLllA-4206 + GCTCTCTGGGTACTACG 17 4192

BCLllA-4207 - CCACAGGGACACTTGCG 17 4193

BCLllA-4208 - GAGACTTAGAGAGCTGG 17 4194

BCLllA-4209 - TTGACAGGGTGCTGCGG 17 4195

BCLllA-4210 - CCGAGGCCGAGGGCCAC 17 4196

BCLllA-4211 + AGGGATCTTTGAGCTGC 17 4197

BCLllA-4212 + AAGTAGATTCTTAATCC 17 4198

BCLllA-4213 - GCGCAGCGGCACGGGAA 17 4199

BCLllA-4214 - GCCGAGGCCGAGGGCCA 17 4200

BCLllA-4215 - AAGATGTGTGGCAGTTT 17 4201

BCLllA-4216 + AGCTAAGGAAGGGATCT 17 4202

BCLllA-4217 + CAG CTCTCTAAGTCTCC 17 4203

BCLllA-4218 + CCTAGAGAAATCCATGG 17 4204

BCLllA-4219 - ACCACGAGAACAGCTCG 17 4205

BCLllA-4220 + G C A AT ATG A ATC CC ATG 17 4206

BCLllA-4221 - CTC C ATG CAG C ACTTC A 17 4207

BCLllA-4222 - TGTCC AAAAAG CTG CTG 17 4208

BCLllA-4223 - GAATACCAGGATCAGTA 17 4209

BCLllA-4224 - TCTCGGGGCGCAGCGGC 17 4210

BCLllA-4225 - AG 1 1 1 I GGA I GAAGC 17 4211

BCLllA-4226 - TCGTGGGCGTGGGCGAC 17 4212

BCLllA-4227 + TCGCGGCCGGGGGCAGG 17 4213

BCLllA-4228 - CTACTTAGAAAGCGAAC 17 4214

BCLllA-4229 + GGGTTATTGTCTGCAAT 17 4215

BCLllA-4230 + CTTGACCGGGGGCTGGG 17 4216

BCLllA-4231 - TGGATTAAGAATCTACT 17 4217

BCLllA-4232 - GGCTTCCGGCCTGGCAG 17 4218

BCLllA-4233 - CTTCCACCAGGTCCTGG 17 4219

BCLllA-4234 + CG CTTC AG CTTG CTG G C 17 4220

BCLllA-4235 - CATAGAGCGCCTGGGGG 17 4221

BCLllA-4236 + CCTGGTGGAAGGCCTCG 17 4222

BCLllA-4237 - TCCACCAGGTCCTGGGC 17 4223

BCLllA-4238 + CTG C A AT ATG A ATC CCA 17 4224

BCLllA-4239 - GCTGGACGGAGGGATCT 17 4225

BCLllA-4240 + TTGACCGGGGGCTGGGA 17 4226 BCLllA-4241 - TTCCCAGCCACCTCTCC 17 4227

BCLllA-4242 + TTTTG AGCTGGGCCTGC 17 4228

BCLllA-4243 - GCTTCTCCACACCGCCC 17 4229

BCLllA-4244 + AGAGAAACCATGCACTG 17 4230

BCLllA-4245 - AGCTGGACGGAGGGATC 17 4231

BCLllA-4246 + CCGGGGAGCTGGCGGTG 17 4232

BCLllA-4247 + ATCCCATGGAGAGGTGG 17 4233

BCLllA-4248 + GTTCCGGGGAGCTGGCG 17 4234

BCLllA-4249 + GACTAAACAGGGGGGGA 17 4235

BCLllA-4250 + TG CCCAG CAG CAG CTTT 17 4236

BCLllA-4251 + GGGATCTTTGAGCTGCC 17 4237

BCLllA-4252 - TCCCAGCCACCTCTCCA 17 4238

BCLllA-4253 - CAGCGGCACGGGAAGTG 17 4239

BCLllA-4254 + TTCCGGGGAGCTGGCGG 17 4240

BCLllA-4255 + TCCTCGTCCCCGTTCTC 17 4241

BCLllA-4256 - GCGGCACGGGAAGTGGA 17 4242

BCLllA-4257 - TGGGCAGCCCCAGCTCG 17 4243

BCLllA-4258 - CGCAGCGGCACGGGAAG 17 4244

BCLllA-4259 - CCGCCCGGGGAGCTGGA 17 4245

BCLllA-4260 + ATGGAGAGGTGGCTGGG 17 4246

BCLllA-4261 + CTCCTCGTCCCCGTTCT 17 4247

BCLllA-4262 - TACTTAGAAAGCGAACA 17 4248

BCLllA-4263 - GGGCAGGCCCAGCTCAA 17 4249

BCLllA-4264 - ACCGCCCGGGGAGCTGG 17 4250

BCLllA-4265 + AAACAGGGGGGGAGTGG 17 4251

BCLllA-4266 + CGGGGGCTGGGAGGGAG 17 4252

BCLllA-4267 + CCGGCCTGGGGACAGCG 17 4253

BCLllA-4268 + TAGGGCTGGGCCGGCCT 17 4254

BCLllA-4269 - AAGAATCTACTTAGAAA 17 4255

BCLllA-4270 + AACAGGGGGGGAGTGGG 17 4256

BCLllA-4271 + ACCGGGGGCTGGGAGGG 17 4257

BCLllA-4272 - GGTCGTGGGCGTGGGCG 17 4258

BCLllA-4273 + GGAGGGGGGGCGTCGCC 17 4259

BCLllA-4274 - GAACGGGGACGAGGAGG 17 4260

BCLllA-4275 + GACCGGGGGCTGGGAGG 17 4261

BCLllA-4276 + GGGAGGGGGGGCGTCGC 17 4262

BCLllA-4277 + GGGGGCTGGGAGGGAGG 17 4263

BCLllA-4278 - AGCGGCACGGGAAGTGG 17 4264

BCLllA-4279 + GATTGCAGAGGAGGGAG 17 4265

BCLllA-4280 + GGGGGGGCGTCGCCAGG 17 4266

BCLllA-4281 + GGATTGCAGAGGAGGGA 17 4267

BCLllA-4282 + GGGCGGATTGCAGAGGA 17 4268 BCLllA-4283 + G CGGATTG CAG AG G AG G 17 4269

BCLllA-4284 - GAGCTGACGGAGAGCGA 17 4270

BCLllA-4285 + GAAAACTGCCACACATC 17 4271

BCLllA-4286 + ATTGCAGAGGAGGGAGG 17 4272

BCLllA-4287 + GGGGCGGATTGCAGAGG 17 4273

BCLllA-4288 + CGGATTGCAGAGGAGGG 17 4274

BCLllA-4289 + AGGGGCGGATTGCAGAG 17 4275

BCLllA-4290 - ACGGGGACGAGGAGGAA 17 4276

BCLllA-4291 + GGAGGAGGGGCGGATTG 17 4277

BCLllA-4292 - CGCTTCTCCACACCGCC 17 4278

BCLllA-4293 - TGACGGAGAGCGAGAGG 17 4279

BCLllA-4294 - AGGAGCTGACGGAGAGC 17 4280

BCLllA-4295 + GCTGGGAGGGAGGAGGG 17 4281

BCLllA-4296 + AGGAGGGGCGGATTGCA 17 4282

BCLllA-4297 + TGTTGGGCATCGCGGCC 17 4283

BCLllA-4298 - CGGGGACGAGGAGGAAG 17 4284

BCLllA-4299 + GGAGGGGCGGATTGCAG 17 4285

BCLllA-4300 - GGAGGAGCTGACGGAGA 17 4286

BCLllA-4301 - GGGACGAGGAGGAAGAG 17 4287

BCLllA-4302 - AGGAGGAGGAGCTGACG 17 4288

BCLllA-4303 - ACGAGGAAGAGGAAGAA 17 4289

BCLllA-4304 - AGGAAGAGGAAGAAGAG 17 4290

BCLllA-4305 - AGGAAGAGGAGGACGAC 17 4291

BCLllA-4306 - AGGAGGACGACGAGGAA 17 4292

BCLllA-4307 - GGAGGAGGAGGAGCTGA 17 4293

BCLllA-4308 - GGAAGAGGAGGACGACG 17 4294

BCLllA-4309 - GGAGGAAGAGGAGGACG 17 4295

BCLllA-4310 - GGAAGAGGAAGAAGAGG 17 4296

BCLllA-4311 - AGGAGGAGGAGGAGCTG 17 4297

BCLllA-4312 - CGAGGAAGAGGAAGAAG 17 4298

BCLllA-4313 - GGACGACGAGGAAGAGG 17 4299

BCLllA-4314 - GGAGGACGACGAGGAAG 17 4300

BCLllA-4315 - CGACGAGGAAGAGGAAG 17 4301

BCLllA-4316 - AGAGGAGGACGACGAGG 17 4302

BCLllA-4317 - AAGAAGAGGAGGAAGAG 17 4303

BCLllA-4318 - AGGAAGAAGAGGAGGAA 17 4304

BCLllA-4319 - AGAGGAAGAAGAGGAGG 17 4305

BCLllA-4320 - AAGAGGAGGAAGAGGAG 17 4306

BCLllA-4321 - AGGAGGAAGAGGAGGAG 17 4307

BCLllA-4322 - GGAAGAAGAGGAGGAAG 17 4308

BCLllA-4323 - AGAAGAGGAGGAAGAGG 17 4309

BCLllA-4324 - AGAGGAGGAAGAGGAGG 17 4310 I BCLllA-4325 | - | GGAGGAAGAGGAGGAGG | 17 | 4311 |

Table 5A provides exemplary targeting domains for knocking out the BCLllA gene by targeting the early coding sequence the BCLllA gene selected according to first tier parameters. The targeting domains are within first 500bp of coding sequence downstream of start codon, good orthogonality, start with G. 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 generates a double strand break (Cas9 nuclease) or a single-strand break (Cas9 nickase). In an embodiment, dual targeting is used to create two double strand breaks to remove the enhancer region in the BCLllA gene, e.g., the first gRNA is used to target upstream (i.e., 5') of the enhancer region in the BCLllA gene and the second gRNA is used to target downstream (i.e., 3') of the enhancer region in the BCLllA gene.

Any of the targeting domains in the table can be used with a N. meningitidis Cas9 (nickase) molecule to generate a single strand break. 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 5A

BCLllA-4331 - CAGGTCACGCCAGAGGA 17 4317

BCLllA-4332 + CCTGGATGCCAACCTCC 17 4318

BCLllA-4333 + A l I GA I C I 1 1 1 1 I CA 17 4319

Table 5B provides exemplary targeting domains for knocking out the BCL11A gene by targeting the early coding sequence the BCL11A gene selected according to second tier parameters. The targeting domains target outside the first 500bp of coding sequence downstream of 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 N. meningitidis Cas9 molecule that generates a double strand break (Cas9 nuclease) or a single- strand break (Cas9 nickase). In an embodiment, dual targeting is used to create two double strand breaks to remove the enhancer region in the BCL11A gene, e.g., the first gRNA is used to target upstream (i.e., 5') of the enhancer region in the BCL11A gene and the second gRNA is used to target downstream (i.e., 3') of the enhancer region in the BCL11A gene.

Table 5B

BCLllA-4339 - AAC ACG CAC AG AAC ACT 17 4325

BCLllA-4340 - TTCCCAGCCACCTCTCC 17 4326

BCLllA-4341 + GGCTGGGAGGGAGGAGG 17 4327

BCLllA-4342 + TCGGACTTGACCGTCATGGG 20 4328

BCLllA-4343 - ATGGCTATGGAGCCTCCCGC 20 4329

BCLllA-4344 + TGCTCCGACGAGGAGGCAAA 20 4330

BCLllA-4345 + TGGCGGGAGGCTCCATAGCC 20 4331

BCLllA-4346 - TGCAACACGCACAGAACACT 20 4332

BCLllA-4347 + ACTTCCGTGTTCGCTTTCTA 20 4333

BCLllA-4348 - TCCTTCCCAGCCACCTCTCC 20 4334

BCLllA-4349 + GGGGGCTGGGAGGGAGGAGG 20 4335

Table 6A provides exemplary targeting domains for removing (e.g., deleting) the enhancer region in the BCLllA gene selected according to first tier parameters. The targeting domains are within a region 5' (51.5 to 51.7kb downstream of transcription start site, TSS) or 3' (65.1 to 65.3kb downstream of TSS) of enhancer, good orthogonality, starts with G. 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 generates a double strand break (Cas9 nuclease) or a single-strand break (Cas9 nickase). In an embodiment, dual targeting is used to create two double strand breaks to remove the enhancer region in the BCLllA gene, e.g., the first gRNA is used to target upstream (i.e., 5') of the enhancer region in the BCLllA gene and the second gRNA is used to target downstream (i.e., 3') of the enhancer region in the BCLllA gene.

Any of the targeting domains in the table can be used with a S. pyogenes Cas9 (nickase) molecule to generate a single strand break. 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. Exemplary gRNA pairs are: BCL11A- 5210 and BCLl lA-5204, BCLl lA-5211 and BCLl lA-5204, BCLl lA-5172 and BCLHA-

5176, BCLl lA-5172 and BCLl lA-5186, BCLl lA-5179 and BCLl lA-5176, or BCLl lA-5179 and BCLl lA-5186. In an embodiment, four gRNAs (e.g., two pairs) are used to target four Cas9 nickases to create four nicks to remove the enhancer region in the BCLllA gene, e.g., the first pair of gRNAs are used to target upstream (i.e., 5') of the enhancer region in the BCLllA gene and the second pair of gRNAs are used to target downstream (i.e., 3') of the enhancer region in the BCLllA gene. For example, gRNA pairs that target upstream (i.e., 5') of the enhancer region in the BCLllA gene (e.g., BCLl lA-5210 and BCLl lA-5204, or BCLl lA-5211 and BCLHA- 5204) can be paired with gRNA pairs that target downstream (i.e., 3') of the enhancer region in the BCLllA gene (e.g., BCLl lA-5172 and BCLl lA-5176, BCLl lA-5172 and BCLl lA-5186, BCLl lA-5179 and BCLl lA-5176, or BCLl lA-5179 and BCLl lA-5186).

Table 6A

Table 6B provides exemplary targeting domains for removing (e.g., deleting) the enhancer region in the BCLllA gene selected according to second tier parameters. The targeting domains are within a region 5' (51.5 to 51.7kb downstream of transcription start site, TSS) or 3' (65.1 to 65.3kb downstream of TSS) of enhancer, good orthogonality, and do not start with G. 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 generates a double strand break (Cas9 nuclease) or a single-strand break (Cas9 nickase). In an embodiment, dual targeting is used to create two double strand breaks to remove the enhancer region in the BCLllA gene, e.g., the first gRNA is used to target upstream (i.e., 5') of the enhancer region in the BCLllA gene and the second gRNA is used to target downstream (i.e., 3') of the enhancer region in the BCLllA gene.

Any of the targeting domains in the table can be used with a S. pyogenes Cas9 (nickase) molecule to generate a single strand break. 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. The table provides exemplary targeting domains for removing (e.g., deleting) the enhancer region in the BCL11A gene selected according to first tier parameters. The targeting domains are within a region 5' (51.5 to 51.7kb downstream of transcription start site, TSS) or 3' (65.1 to 65.3kb downstream of TSS) of enhancer, good orthogonality, starts with G. 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 generates a double strand break (Cas9 nuclease) or a single-strand break (Cas9 nickase). In an embodiment, dual targeting is used to create two double strand breaks to remove the enhancer region in the BCL11A gene, e.g., the first gRNA is used to target upstream (i.e., 5') of the enhancer region in the BCL11A gene and the second gRNA is used to target downstream (i.e., 3') of the enhancer region in the BCL11A gene.

Table 6B

BCLllA-5179 + AATACTTACTGTACTGC 17 3' 4343

BCLllA-5180 + ACA ACTTGTGTTG CACT 17 5' 4344

BCLllA-5181 + ATACTTACTGTACTGCA 17 3' 4345

BCLllA-5182 + ATTCACTGGAAACCCTGTTA 20 3' 4346

BCLllA-5183 + ATTTAAGACGGGAAAAC 17 5' 4347

BCLllA-5184 + CACTGGAAACCCTGTTA 17 3' 4348

BCLllA-5185 + CTACTTATACAATTCAC 17 3' 4349

BCLllA-5186 - CTATTTACAGCCATAAC 17 3' 4350

BCLllA-5187 - TAAGAAAGCAGTGTAAGGCT 20 5' 4351

BCLllA-5188 + TAC ACA ACTTGTGTTG CACT 20 5' 4352

BCLllA-5189 + TACTGTACTGCAGGGGAATT 20 3' 4353

BCLllA-5190 + TACTTACTGTACTGCAG 17 3' 4354

BCLllA-5191 + TGTACTGCAGGGG A ATT 17 3' 4355

Table 6C provides exemplary targeting domains for removing (e.g., deleting) the enhancer region in the BCLllA gene selected according to third tier parameters. The targeting domains are within a region 5' (51.5 to 51.7kb downstream of transcription start site, TSS) or 3' (65.1 to 65.3kb downstream of TSS) of enhancer and start with G. 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 generates a double strand break (Cas9 nuclease) or a single- strand break (Cas9 nickase). In an

embodiment, dual targeting is used to create two double strand breaks to remove the enhancer region in the BCLllA gene, e.g., the first gRNA is used to target upstream (i.e., 5') of the enhancer region in the BCLllA gene and the second gRNA is used to target downstream (i.e., 3') of the enhancer region in the BCLllA gene.

Any of the targeting domains in the table can be used with a S. pyogenes Cas9 (nickase) molecule to generate a single strand break. 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. The table provides exemplary targeting domains for removing (e.g., deleting) the enhancer region in the BCLllA gene selected according to first tier parameters. The targeting domains are within a region 5' (51.5 to 51.7kb downstream of transcription start site, TSS) or 3' (65.1 to 65.3kb downstream of TSS) of enhancer, good orthogonality, starts with G. 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 generates a double strand break (Cas9 nuclease) or a single-strand break (Cas9 nickase). In an embodiment, dual targeting is used to create two double strand breaks to remove the enhancer region in the BCL11A gene, e.g., the first gRNA is used to target upstream (i.e., 5') of the enhancer region in the BCL11A gene and the second gRNA is used to target downstream (i.e., 3') of the enhancer region in the BCL11A gene.

Table 6C

Table 6D provides exemplary targeting domains for removing (e.g., deleting) the enhancer region in the BCL11A gene selected according to forth tier parameters. The targeting domains are within a region 5' (51.5 to 51.7kb downstream of transcription start site, TSS) or (65.1 to 65.3kb downstream of TSS) of enhancer and do not start with G. 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 generates a double strand break (Cas9 nuclease) or a single-strand break (Cas9 nickase). In an embodiment, dual targeting is used to create two double strand breaks to remove the enhancer region in the BCLllA gene, e.g., the first gRNA is used to target upstream (i.e., 5') of the enhancer region in the BCLllA gene and the second gRNA is used to target downstream (i.e., 3') of the enhancer region in the BCLllA gene.

Any of the targeting domains in the table can be used with a S. pyogenes Cas9 (nickase) molecule to generate a single strand break. 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. The table provides exemplary targeting domains for removing (e.g., deleting) the enhancer region in the BCLllA gene selected according to first tier parameters. The targeting domains are within a region 5' (51.5 to 51.7kb downstream of transcription start site, TSS) or 3' (65.1 to 65.3kb downstream of TSS) of enhancer, good orthogonality, starts with G. 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 generates a double strand break (Cas9 nuclease) or a single-strand break (Cas9 nickase). In an embodiment, dual targeting is used to create two double strand breaks to remove the enhancer region in the BCLllA gene, e.g., the first gRNA is used to target upstream (i.e., 5') of the enhancer region in the BCLllA gene and the second gRNA is used to target downstream (i.e., 3') of the enhancer region in the BCLllA gene.

Table 6D

Table 7A provides exemplary targeting domains for removing (e.g., deleting) the enhancer region in the BCLllA gene selected according to first tier parameters. The targeting domains are within a region 5' (51.5 to 51.7kb downstream of transcription start site, TSS) or 3' (65.1 to 65.3kb downstream of TSS) of enhancer, good orthogonality, starts with G. 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 generates a double strand break (Cas9 nuclease) or a single- strand break (Cas9 nickase). In an embodiment, dual targeting is used to create two double strand breaks to remove the enhancer region in the BCLllA gene, e.g., the first gRNA is used to target upstream (i.e., 5') of the enhancer region in the BCLllA gene and the second gRNA is used to target downstream (i.e., 3') of the enhancer region in the BCLllA gene.

Table 7A

Table 7B provides exemplary targeting domains for removing (e.g., deleting) the enhancer region in the BCLllA gene selected according to second tier parameters. The targeting domains are within a region 5' (51.5 to 51.7kb downstream of transcription start site, TSS) or 3' (65.1 to 65.3kb downstream of TSS) of enhancer, good orthogonality, and do not start with G. 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 generates a double strand break (Cas9 nuclease) or a single- strand break (Cas9 nickase). In an embodiment, dual targeting is used to create two double strand breaks to remove the enhancer region in the BCLllA gene, e.g., the first gRNA is used to target upstream (i.e., 5') of the enhancer region in the BCLllA gene and the second gRNA is used to target downstream (i.e., 3') of the enhancer region in the BCLllA gene.

Any of the targeting domains in the table can be used with a S. aureus Cas9 (nickase) molecule to generate a single strand break. 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. The table provides exemplary targeting domains for removing (e.g., deleting) the enhancer region in the BCLllA gene selected according to first tier parameters. The targeting domains are within a region 5' (51.5 to 51.7kb downstream of transcription start site, TSS) or 3' (65.1 to 65.3kb downstream of TSS) of enhancer, good orthogonality, starts with G. 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 generates a double strand break (Cas9 nuclease) or a single-strand break (Cas9 nickase). In an embodiment, dual targeting is used to create two double strand breaks to remove the enhancer region in the BCLllA gene, e.g., the first gRNA is used to target upstream (i.e., 5') of the enhancer region in the BCLllA gene and the second gRNA is used to target downstream (i.e., 3') of the enhancer region in the BCLllA gene.

Table 7B

Table 7C provides exemplary targeting domains for removing (e.g., deleting) the enhancer region in the BCL11A gene selected according to third tier parameters. The targeting domains are within a region 5' (51.5 to 51.7kb downstream of transcription start site, TSS) or 3' (65.1 to 65.3kb downstream of TSS) of enhancer and start with G. 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 generates a double strand break (Cas9 nuclease) or a single-strand break (Cas9 nickase). In an embodiment, dual targeting is used to create two double strand breaks to remove the enhancer region in the BCL11A gene, e.g., the first gRNA is used to target upstream (i.e., 5') of the enhancer region in the BCL11A gene and the second gRNA is used to target downstream (i.e., 3') of the enhancer region in the BCL11A gene.

Any of the targeting domains in the table can be used with a S. aureus Cas9 (nickase) molecule to generate a single strand break. 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. The table provides exemplary targeting domains for removing (e.g., deleting) the enhancer region in the BCL11A gene selected according to first tier parameters. The targeting domains are within a region 5' (51.5 to 51.7kb downstream of transcription start site, TSS) or 3' (65.1 to 65.3kb downstream of TSS) of enhancer, good orthogonality, starts with G. 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 generates a double strand break (Cas9 nuclease) or a single-strand break (Cas9 nickase). In an embodiment, dual targeting is used to create two double strand breaks to remove the enhancer region in the BCL11A gene, e.g., the first gRNA is used to target upstream (i.e., 5') of the enhancer region in the BCL11A gene and the second gRNA is used to target downstream (i.e., 3') of the enhancer region in the BCL11A gene.

Table 7C

Table 7D provides exemplary targeting domains for removing (e.g., deleting) the enhancer region in the BCLllA gene selected according to forth tier parameters. The targeting domains are within a region 5' (51.5 to 51.7kb downstream of transcription start site, TSS) or 3' (65.1 to 65.3kb downstream of TSS) of enhancer and do not start with G. 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 generates a double strand break (Cas9 nuclease) or a single-strand break (Cas9 nickase). In an embodiment, dual targeting is used to create two double strand breaks to remove the enhancer region in the BCLllA gene, e.g., the first gRNA is used to target upstream (i.e., 5') of the enhancer region in the BCLllA gene and the second gRNA is used to target downstream (i.e., 3') of the enhancer region in the BCLllA gene.

Table 7D

Length

BCLllA-5256 + AAAAATTTAAGACGGGAAAA 20 5' 4420

BCLllA-5257 + AAAACAGGAAGATGCATTCT 20 5' 4421

BCLllA-5258 - AAAA 1 AGAAA 1 I MA 17 3' 4422

BCLllA-5259 + AAAATACTTACTGTACTG CA 20 3' 4423

BCLllA-5260 + AAAATTTAAGACGGGAAAAC 20 5' 4424

BCLllA-5261 + AAACAGGAAGATGCATT 17 5' 4425

BCLllA-5262 - AAAGG I 111 I GAAI I A 20 5' 4426

BCLllA-5263 + AAATACTTACTGTACTG 17 3' 4427

BCLllA-5264 + AAATACTTACTGTACTGCAG 20 3' 4428

BCLllA-5265 - AAGAAAGCAGTGTAAGG 17 5' 4429

BCLllA-5266 - AAGGCIGI 11 IGGAAIG 17 5' 4430

BCLllA-5267 - AAGIAI 11 ICI 1 ICAI 1 17 3' 4431

BCLllA-5268 + AATACTTACTGTACTGC 17 3' 4432

BCLllA-5269 - A ATTAG AATAAAAG G CTGTT 20 5' 4433

BCLllA-5270 + AAI IAI 111 AC 1 AG 1 AA 11 20 5' 4434

BCLllA-5271 + AATTTAAGACGGGAAAA 17 5' 4435

BCLllA-5272 + A C AG G A AG ATG C ATTCT 17 5' 4436

BCLllA-5273 - ACAGTAAGTATTTTCTTTCA 20 3' 4437

BCLllA-5274 + ACATAAAAATTTAAGAC 17 5' 4438

BCLllA-5275 + ACTTTCTAGTTTTG CTTAAC 20 3' 4439

BCLllA-5276 + AGAAAATACTTACTGTACTG 20 3' 4440

BCLllA-5277 - AG AATAAAAGG CTGTTT 17 5' 4441

BCLllA-5278 - A AAAA 1 AGAAAG 1 I MA 20 3' 4442

BCLllA-5279 - AGTAAGTATTTTCTTTCATT 20 3' 4443

BCLllA-5280 - A IAI 11 ICI 1 ICAI IG 17 3' 4444

BCLllA-5281 - AGTGAATTGTATAAGTAGCA 20 3' 4445

BCLllA-5282 + ATACTTACTGTACTG CA 17 3' 4446

BCLllA-5283 + ATCTCACATAAAAATTTAAG 20 5' 4447

BCLllA-5284 - ATTAAGAAAGCAGTGTAAGG 20 5' 4448

BCLllA-5285 - ATTAG AATAAAAG G CTGTTT 20 5' 4449

BCLllA-5286 + Al IAI 111 ACI AG I AAI IA 20 5' 4450

BCLllA-5287 + ATTTAAGACGGGAAAAC 17 5' 4451

BCLllA-5288 + Al 111 AC 1 AG 1 AA 1 IA 17 5' 4452

BCLllA-5289 - Al 11 ICAIGI 1 AAGCAAAAC 20 3' 4453

BCLllA-5290 + CACATAAAAATTTAAGA 17 5' 4454

BCLllA-5291 - CAGIAAGIAI 11 ICI 1 ICAI 20 3' 4455

BCLllA-5292 - CCGTCTTAAATTTTTAT 17 5' 4456

BCLllA-5293 + CTCACATAAAAATTTAAGAC 20 5' 4457

BCLllA-5294 - 1 AAAAGGCI 111 IGGAAIG 20 5' 4458

BCLllA-5295 - 1 AAGIAI I I ICI 1 ICAI 17 3' 4459

BCLllA-5296 - 1 AAGIAI I I ICI 1 ICAI IGG 20 3' 4460 BCLllA-5297 - TAATTCACTAGTAAAATAAT 20 5' 4461

BCLllA-5298 + TACTTACTGTACTG CAG 17 3' 4462

BCLllA-5299 - TAG A ATAAAAG G CTGTT 17 5' 4463

BCLllA-5300 + TATTTTACTAGTGAATT 17 5' 4464

BCLllA-5301 + TCACATAAAAATTTAAG 17 5' 4465

BCLllA-5302 + TCTCACATAAAAATTTAAGA 20 5' 4466

BCLllA-5303 + I G I 1 I CA I 1 1 1 1 I GC I GACA 20 3' 4467

BCLllA-5304 - TGTTTTGGAATGTAGAGAGG 20 5' 4468

BCLllA-5305 - 1 I AAA I 1 1 1 I A I G I GAG 17 5' 4469

BCLllA-5306 + TTATTCTAATTATTTTACTA 20 5' 4470

BCLllA-5307 - TTCACTAGTAAAATAAT 17 5' 4471

BCLllA-5308 - TTCATGTTAAG CAAAAC 17 3' 4472

BCLllA-5309 + 1 I CA I 1 1 1 1 I GC I GACA 17 3' 4473

BCLllA-5310 - 1 I CCCG I C I I AAA I 1 1 1 I A I 20 5' 4474

BCLllA-5311 + TTCTAATTATTTTACTA 17 5' 4475

BCLllA-5312 + TTCTAGTTTTG CTTAAC 17 3' 4476

BCLllA-5313 - TTCTGTGTCAG CAAAAA 17 3' 4477

BCLllA-5314 - TTTGGAATGTAGAGAGG 17 5' 4478

BCLllA-5315 - TTTGGAATGTAGAGAGGCAG 20 5' 4479

Table 8 provides exemplary targeting domains for removing (e.g., deleting) the enhancer region in the BCLllA gene selected according to first tier parameters. The targeting domains are within a region 5' (51.5 to 51.7kb downstream of transcription start site, TSS) or 3' (65.1 to 65.3kb downstream of TSS) of enhancer, good orthogonality, starts with G. 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 generates a double strand break (Cas9 nuclease) or a single-strand break (Cas9 nickase). In an embodiment, dual targeting is used to create two double strand breaks to remove the enhancer region in the BCLllA gene, e.g., the first gRNA is used to target upstream (i.e., 5') of the enhancer region in the BCLllA gene and the second gRNA is used to target downstream (i.e., 3') of the enhancer region in the BCLllA gene.

Table 8

Table 9A provides exemplary targeting domains for knocking down expression of the

BCL11A gene according to first tier parameters. The targeting domains are between 500bp upstream and 500bp downstream of transcription start site, good orthogonality, starts with G. 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 eiCas9 molecule to cause a steric block at the target region, e.g., between 500bp upstream and 500bp downstream of transcription start site to block transcription resulting in the repression of the BCL11A gene. Alternatively, any of the targeting domains in the table can be used with a S. pyogenes eiCas9 fused to a transcriptional repressor to decrease transcription and therefore downregulate gene expression.

Table 9A

Table 9B provides exemplary targeting domains for knocking down expression of the BCL11A gene according to second tier parameters. The targeting domains are between 500bp upstream and 500bp downstream of transcription start site, good orthogonality and do not start with G. 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 eiCas9 molecule to cause a steric block at the target region, e.g., between 500bp upstream and 500bp downstream of transcription start site to block transcription resulting in the repression of the BCL11A gene. Alternatively, any of the targeting domains in the table can be used with a S. pyogenes eiCas9 fused to a transcriptional repressor to decrease transcription and therefore downregulate gene expression.

Table 9B

BCLllA-4380 + TTTACCTCGACTCTCGG 17 4512

BCLllA-4381 - TTTAGAGTCCGCGTGTG 17 4513

Table 9C provides exemplary targeting domains for knocking down expression of the BCL11A gene according to third tier parameters. The targeting domains are between 500bp upstream and 500bp downstream of transcription start site and start with G. 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 eiCas9 molecule to cause a steric block at the target region, e.g., between 500bp upstream and 500bp downstream of transcription start site to block transcription resulting in the repression of the BCL11A gene. Alternatively, any of the targeting domains in the table can be used with a S. pyogenes eiCas9 fused to a transcriptional repressor to decrease transcription and therefore downregulate gene expression.

Table 9C

BCLllA-4403 + GAGAGAAGAGAGATAGA 17 4535

BCLllA-4404 + GAGAGAAGGGGAGGAGGGAA 20 4536

BCLllA-4405 + GAGAGAGAGAAGAGAGATAG 20 4537

BCLllA-4406 + G AG AG AG ATG A A A A A A A 17 4538

BCLllA-4407 + GAGCAGGAGAGAAGGGG 17 4539

BCLllA-4408 + GAGCAGGAGAGAAGGGGAGG 20 4540

BCLllA-4409 + GAGCCGGGTTAGAAAGA 17 4541

BCLllA-4410 + GAGGGGAGGGGGCGCTG 17 4542

BCLllA-4411 + GAGGGGCGGGCCGAGGGGAG 20 4543

BCLllA-4412 + GAGGGGGAGGTGCGGGG 17 4544

BCLllA-4413 + GAGGGGGAGGTGCGGGGCGG 20 4545

BCLllA-4414 - GAG GTA A A AG AG ATA A A 17 4546

BCLllA-4415 - GAGTCCGCGTGTGTGGG 17 4547

BCLllA-4416 - GAGTCTCCTTCTTTCTAACC 20 4548

BCLllA-4417 - GA I GAAGA I A I 1 1 1 C I 17 4549

BCLllA-4418 - GCAAAAGCGAGGGGGAGAGA 20 4550

BCLllA-4419 - GCACCTCCCCCTCCCCGCAC 20 4551

BCLllA-4420 - G CACTTG AACTTG C AG CTC A 20 4552

BCLllA-4421 + GCAGGGAAGATGAATTG 17 4553

BCLllA-4422 + GCAGGGCGAGCAGGAGAGAA 20 4554

BCLllA-4423 + G C AG GG GTG G GAG G AAA 17 4555

BCLllA-4424 + GCAGGGGTGGGAGGAAAGGG 20 4556

BCLllA-4425 + GCCAATGGCCAGTGCGGGGA 20 4557

BCLllA-4426 - GCCACCCCTTTCTTCTCTCC 20 4558

BCLllA-4427 + GCCAGACGCGGCCCCCG 17 4559

BCLllA-4428 - GCCCCAGCGCCCCCTCCCCT 20 4560

BCLllA-4429 + GCCCCCGGGGGAGGGGC 17 4561

BCLllA-4430 - GCCCGCCCCTCCCCCGG 17 4562

BCLllA-4431 + GCCGAGGGGAGGGGGCGCTG 20 4563

BCLllA-4432 + GCCGCGGCGGTGGCGTGGCC 20 4564

BCLllA-4433 + GCCGGGAGAGAAGAAAG 17 4565

BCLllA-4434 + GCCGGGAGAGAAGAAAGGGG 20 4566

BCLllA-4435 + GCGAGACATGGTGGGCTGCG 20 4567

BCLllA-4436 + GCGCAGGGAAGATGAATTGT 20 4568

BCLllA-4437 + GCGCCGCGGCGGTGGCG 17 4569

BCLllA-4438 - GCGCTCGCTGCGGCCAC 17 4570

BCLllA-4439 + GCGGCCCCCGGGGGAGGGGC 20 4571

BCLllA-4440 - GCGGCGCTCGCTGCGGCCAC 20 4572

BCLllA-4441 + GCGGCGGCGGCGGCGGC 17 4573

BCLllA-4442 + GCGGCGGCGGCGGCGGCGGC 20 4574

BCLllA-4443 + GCGGCGGCGGCGGCGGCGGG 20 4575

BCLllA-4444 + GCGGCGGCGGCGGCGGG 17 4576 BCLllA-4445 + GCGGCGGGCGGACGACGGCT 20 4577

BCLllA-4446 + GCGGCGGTGGCGTGGCC 17 4578

BCLllA-4447 + GCGGGCGGCGGCGGCGG 17 4579

BCLllA-4448 + GCGGGCGGCGGCGGCGGCGG 20 4580

BCLllA-4449 + GCGGGGAGGGGGAGGTG 17 4581

BCLllA-4450 + GCGTGGCCGGGAGAGAAGAA 20 4582

BCLllA-4451 + GCTCCCCCCCACACACG 17 4583

BCLllA-4452 + GCTGGGGTTTGCCTTGCTTG 20 4584

BCLllA-4453 + GGACAAGCCAATGGCCAGTG 20 4585

BCLllA-4454 + GGACACACATCAGGGGC 17 4586

BCLllA-4455 + GGACAGAGACACACAAAACA 20 4587

BCLllA-4456 + GGACGCCAGACGCGGCCCCC 20 4588

BCLllA-4457 - GGACTAGAAGCAAAAGCGAG 20 4589

BCLllA-4458 + GGAGAGAAGAAAGGGGTGGC 20 4590

BCLllA-4459 + GGAGAGAAGGGGAGGAGGGA 20 4591

BCLllA-4460 + GGAGAGCCGGGTTAGAAAGA 20 4592

BCLllA-4461 + GGAGGGGCGGGCCGAGGGGA 20 4593

BCLllA-4462 + GGAGGGGGAGGTGCGGGGCG 20 4594

BCLllA-4463 + GGAGGGGGCGCTGGGGCCGC 20 4595

BCLllA-4464 + GGCAGGGCGAGCAGGAGAGA 20 4596

BCLllA-4465 + GGCAGGGGTGGGAGGAA 17 4597

BCLllA-4466 - GGCCACTGGTGAGCCCG 17 4598

BCLllA-4467 + GGCCCCCGGGGGAGGGG 17 4599

BCLllA-4468 - GGCCCGCCCCTCCCCCG 17 4600

BCLllA-4469 + GGCCGAGGGGAGGGGGCGCT 20 4601

BCLllA-4470 + GGCCGCAGCGAGCGCCG 17 4602

BCLllA-4471 + GGCCGCAGCGAGCGCCGCGG 20 4603

BCLllA-4472 + GGCCGCGGGCTCACCAG 17 4604

BCLllA-4473 + GGCCGGGAGAGAAGAAA 17 4605

BCLllA-4474 + GGCGAGACATGGTGGGCTGC 20 4606

BCLllA-4475 + GG CG AG CAGG AG AG AAG 17 4607

BCLllA-4476 + GGCGAGCAGGAGAGAAGGGG 20 4608

BCLllA-4477 + GGCGCAGGGAAGATGAATTG 20 4609

BCLllA-4478 + GGCGGCGGCGGCGGCGG 17 4610

BCLllA-4479 + GGCGGCGGCGGCGGCGGCGG 20 4611

BCLllA-4480 + GGCGGGCCGAGGGGAGG 17 4612

BCLllA-4481 + GGCTGCGGGGCGGGCGG 17 4613

BCLllA-4482 + GGCTGCGGGGCGGGCGGCGG 20 4614

BCLllA-4483 + GGGAGAGAAGAAAGGGG 17 4615

BCLllA-4484 + GGGAGGAAAGGGTGGGG 17 4616

BCLllA-4485 + GGGAGGGGCGGGCCGAG 17 4617

BCLllA-4486 + GGGAGGGGCGGGCCGAGGGG 20 4618 BCLllA-4487 + GGGAGGGGGAGGTGCGGGGC 20 4619

BCLllA-4488 + GGGAGGGGGCGCTGGGGCCG 20 4620

BCLllA-4489 + GGGAGGTGCGGGGCGGG 17 4621

BCLllA-4490 + GGGCCGAGGGGAGGGGGCGC 20 4622

BCLllA-4491 + GGGCGAGCAGGAGAGAA 17 4623

BCLllA-4492 + GGGCGGGCCGAGGGGAG 17 4624

BCLllA-4493 + GGGGAAGCTCACACCAA 17 4625

BCLllA-4494 + GGGGAGGGGCGGGCCGA 17 4626

BCLllA-4495 + GGGGAGGGGGAGGTGCG 17 4627

BCLllA-4496 + GGGGAGGGGGAGGTGCGGGG 20 4628

BCLllA-4497 + GGGGAGGTGCGGGGCGG 17 4629

BCLllA-4498 - GGGGCCGCGTCTGGCGTCCG 20 4630

BCLllA-4499 + GGGGCGGGCCGAGGGGA 17 4631

BCLllA-4500 + GGGGCGGGCGGCGGCGG 17 4632

BCLllA-4501 + GGGGCGGGCGGCGGCGGCGG 20 4633

BCLllA-4502 + GGGGGAGGGGCGGGCCG 17 4634

BCLllA-4503 + GGGGGAGGTGCGGGGCG 17 4635

BCLllA-4504 + GGGGGCGCTGGGGCCGC 17 4636

BCLllA-4505 + GGGGTGGCAGGGGTGGG 17 4637

BCLllA-4506 + GGGGTGGGAGGAAAGGG 17 4638

BCLllA-4507 + GGGGTGGGAGGAAAGGGTGG 20 4639

BCLllA-4508 + G G G GTTTG CCTTG CTTG 17 4640

BCLllA-4509 + GGGTGGGAGGAAAGGGT 17 4641

BCLllA-4510 + GGGTGGGAGGAAAGGGTGGG 20 4642

BCLllA-4511 - G GT A A A AG AG AT A A AG G 17 4643

BCLllA-4512 + GGTGGCAGGGGTGGGAGGAA 20 4644

BCLllA-4513 + GGTGGGAGGAAAGGGTG 17 4645

BCLllA-4514 + GGTGGGAGGAAAGGGTGGGG 20 4646

BCLllA-4515 + GGTTCCAGATGGGATGA 17 4647

BCLllA-4516 - GTATTATTTCTAATTTATTT 20 4648

BCLllA-4517 - GTCGAGGTAAAAGAGATAAA 20 4649

BCLllA-4518 + GTGCGGGGAGGGGGAGGTGC 20 4650

BCLllA-4519 + GTGCGGGGCGGGGGGCTCCG 20 4651

BCLllA-4520 + GTGGCAGGGGTGGGAGGAAA 20 4652

BCLllA-4521 + GTGGCCGGGAGAGAAGAAAG 20 4653

BCLllA-4522 + GTGGGAGGAAAGGGTGG 17 4654

BCLllA-4523 + GTGGGCTGCGGGGCGGG 17 4655

BCLllA-4524 + GTGGGCTGCGGGGCGGGCGG 20 4656

BCLllA-4525 - GTGTGTGGGGGGGAGCA 17 4657

Table 9D provides exemplary targeting domains for knocking down expression of the BCLllA gene according to forth tier parameters. The targeting domains are between 500bp upstream and 500bp downstream of transcription start site and do not start with G. 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 eiCas9 molecule to cause a steric block at the target region, e.g., between 500bp upstream and 500bp downstream of transcription start site to block transcription resulting in the repression of the BCL11A gene. Alternatively, any of the targeting domains in the table can be used with a S. pyogenes eiCas9 fused to a transcriptional repressor to decrease transcription and therefore downregulate gene expression.

Table 9D

BCLllA-4553 + ACAAGCCAATGGCCAGTGCG 20 4685

BCLllA-4554 + ACACACAAAACATGGGC 17 4686

BCLllA-4555 + ACACCAATGGACACACATCA 20 4687

BCLllA-4556 + AC ATG GGCAGGGCGAGC 17 4688

BCLllA-4557 + ACCAATGGACACACATC 17 4689

BCLllA-4558 - ACCCCAGCACTTAAGCAAAC 20 4690

BCLllA-4559 - ACCCCTTTCTTCTCTCC 17 4691

BCLllA-4560 + ACGCCAGACGCGGCCCC 17 4692

BCLllA-4561 + ACGCCAGACGCGGCCCCCGG 20 4693

BCLllA-4562 + ACGCGGCCCCCGGGGGA 17 4694

BCLllA-4563 + ACGG CA ATG GTTCC AG A 17 4695

BCLllA-4564 - ACTAG A AG CAAAAGCGA 17 4696

BCLllA-4565 - AC 1 A 1 AAGA 1 A 1 1 1 I C I C 20 4697

BCLllA-4566 - ACTTG AACTTG CAG CTC 17 4698

BCLllA-4567 - ACTTG AACTTG CAG CTCAG G 20 4699

BCLllA-4568 - AGAAAAACCTCCGAGAGTCG 20 4700

BCLllA-4569 + AGAAGAAAGGGGTGGCA 17 4701

BCLllA-4570 + AGAAGGGGAGGAGGGAA 17 4702

BCLllA-4571 + AGACACACAAAACATGGGCA 20 4703

BCLllA-4572 + AGACATGGTGGGCTGCG 17 4704

BCLllA-4573 + AGACATGGTGGGCTGCGGGG 20 4705

BCLllA-4574 + AGACCAGGACAAGCCAA 17 4706

BCLllA-4575 + AGACGCGGCCCCCGGGGGAG 20 4707

BCLllA-4576 + AGAGAAGAAAGGGGTGGCAG 20 4708

BCLllA-4577 + AGAGAAGGGGAGGAGGGAAG 20 4709

BCLllA-4578 + AGAGACACACAAAACAT 17 4710

BCLllA-4579 + AGAGAGAAGAGAGATAG 17 4711

BCLllA-4580 + AGAGAGAGAAGAGAGATAGA 20 4712

BCLllA-4581 + AGAGAGAGAGATGAAAAAAA 20 4713

BCLllA-4582 - AGAGTCCGCGTGTGTGG 17 4714

BCLllA-4583 - AGCAAAAGCGAGGGGGAGAG 20 4715

BCLllA-4584 + AGCAGGAGAGAAGGGGAGGA 20 4716

BCLllA-4585 + AG CCA ATG GCCAGTG CG 17 4717

BCLllA-4586 + AGCCAATGGCCAGTGCGGGG 20 4718

BCLllA-4587 - AGCCCCTGATGTGTGTCCAT 20 4719

BCLllA-4588 + AGCGAGCGCCGCGGCGG 17 4720

BCLllA-4589 + AG CTG C AAGTTC AAGTG 17 4721

BCLllA-4590 - AG G ACTAG AAG C AAAAG CG A 20 4722

BCLllA-4591 + AGGAGAGAAGGGGAGGA 17 4723

BCLllA-4592 + AGGGCGAGCAGGAGAGA 17 4724

BCLllA-4593 + AGGGGCGGGCCGAGGGG 17 4725

BCLllA-4594 + AGGGGCGGGCCGAGGGGAGG 20 4726 BCLllA-4595 + AGGGGGAGGTGCGGGGC 17 4727

BCLllA-4596 + AGGGGGAGGTGCGGGGCGGG 20 4728

BCLllA-4597 + AGGGGGCGCTGGGGCCG 17 4729

BCLllA-4598 + AGGGGTGGGAGGAAAGGGTG 20 4730

BCLllA-4599 - AGGTAAAAGAGATAAAG 17 4731

BCLllA-4600 - AGTCCGCGTGTGTGGGG 17 4732

BCLllA-4601 - AGTCGAGGTAAAAGAGATAA 20 4733

BCLllA-4602 + AGTGCGGGGAGGGGGAGGTG 20 4734

BCLllA-4603 + AGTG GCCG CAG CG AG CG CCG 20 4735

BCLllA-4604 + ATAATTATTATTACTATTAT 20 4736

BCLllA-4605 + ATCTCTTTTACCTCGACTCT 20 4737

BCLllA-4606 + ATGGCCAGTGCGGGGAG 17 4738

BCLllA-4607 + ATGGTGGGCTGCGGGGC 17 4739

BCLllA-4608 + ATGGTGGGCTGCGGGGCGGG 20 4740

BCLllA-4609 + ATTATTATTACTATTAT 17 4741

BCLllA-4610 - ATTTTAG AGTCCG CGTGTGT 20 4742

BCLllA-4611 - CAAAAGCGAGGGGGAGAGAG 20 4743

BCLllA-4612 + CAAAAGTG CATACACG G C AA 20 4744

BCLllA-4613 + CAAG CCA ATG GCCAGTG 17 4745

BCLllA-4614 + CAATG G AC ACAC ATC AG 17 4746

BCLllA-4615 + CAATG G CCAGTG CG GG G 17 4747

BCLllA-4616 + CAATGGCCAGTGCGGGGAGG 20 4748

BCLllA-4617 + CAATG GTTCC AG ATGG G ATG 20 4749

BCLllA-4618 + CACACAAAACATGGGCA 17 4750

BCLllA-4619 + CACACCAATGGACACACATC 20 4751

BCLllA-4620 + CACCAATGGACACACATCAG 20 4752

BCLllA-4621 - CACCG CCG CGG CG CTCG CTG 20 4753

BCLllA-4622 - CACTGGCCATTGGCTTGTCC 20 4754

BCLllA-4623 - C ACTTG AACTTG CAG CTCAG 20 4755

BCLllA-4624 + CAGACGCGGCCCCCGGGGGA 20 4756

BCLllA-4625 + CAGAGACACACAAAACA 17 4757

BCLllA-4626 - CAG G ACTAG AAG CAAAAG CG 20 4758

BCLllA-4627 + CAGGAGAGAAGGGGAGG 17 4759

BCLllA-4628 + C AG G G A AG ATG A ATTGT 17 4760

BCLllA-4629 + CAGGGCGAGCAGGAGAGAAG 20 4761

BCLllA-4630 + CAGGGGTGGGAGGAAAGGGT 20 4762

BCLllA-4631 + CATGGTGGGCTGCGGGG 17 4763

BCLllA-4632 + CCAATGGACACACATCA 17 4764

BCLllA-4633 + CCAATGGCCAGTGCGGGGAG 20 4765

BCLllA-4634 + CCAGACGCGGCCCCCGG 17 4766

BCLllA-4635 + CCAGACGCGGCCCCCGGGGG 20 4767

BCLllA-4636 - CCAGCACTTAAGCAAAC 17 4768 BCLllA-4637 - CCAGCGCCCCCTCCCCT 17 4769

BCLllA-4638 + CCAGTGCGGGGAGGGGG 17 4770

BCLllA-4639 - CCCAGCACTTAAGCAAA 17 4771

BCLllA-4640 - CCCCCGGGGGCCGCGTC 17 4772

BCLllA-4641 - CCCCTCCCCGCACTGGCCAT 20 4773

BCLllA-4642 + CCCGGGGGAGGGGCGGGCCG 20 4774

BCLllA-4643 + CCCGTTTG CTTAAGTG C 17 4775

BCLllA-4644 - CCCTCGGCCCGCCCCTCCCC 20 4776

BCLllA-4645 - CCCTGATGTGTGTCCAT 17 4777

BCLllA-4646 + CCGAGGGGAGGGGGCGC 17 4778

BCLllA-4647 - CCGCGTGTGTGGGGGGGAGC 20 4779

BCLllA-4648 + CCGGGGGAGGGGCGGGCCGA 20 4780

BCLllA-4649 + CCGTTTG CTTAAGTG CT 17 4781

BCLllA-4650 - CCTCCCCCGGGGGCCGCGTC 20 4782

BCLllA-4651 - CCTCCCCCTCCCCGCAC 17 4783

BCLllA-4652 - CCTCGGCCCGCCCCTCCCCC 20 4784

BCLllA-4653 + CCTGCTCCCCCCCACACACG 20 4785

BCLllA-4654 + CGAGACATGGTGGGCTG 17 4786

BCLllA-4655 + CGAGCGCCGCGGCGGTGGCG 20 4787

BCLllA-4656 + CGAGGGGAGGGGGCGCT 17 4788

BCLllA-4657 - CGAGGTAAAAGAGATAA 17 4789

BCLllA-4658 - CGAGGTAAAAGAGATAAAGG 20 4790

BCLllA-4659 - CG C ACTTG AACTTG CAG CTC 20 4791

BCLllA-4660 + CG CAG CG AG CG CCG CG G 17 4792

BCLllA-4661 + CGCAGCGAGCGCCGCGGCGG 20 4793

BCLllA-4662 + CGCCAGACGCGGCCCCC 17 4794

BCLllA-4663 - CGCCGCGGCGCTCGCTG 17 4795

BCLllA-4664 + CGCCGCGGCGGTGGCGTGGC 20 4796

BCLllA-4665 + CGCGGCCCCCGGGGGAG 17 4797

BCLllA-4666 + CGCGGCCCCCGGGGGAGGGG 20 4798

BCLllA-4667 + CGCGGCGGTGGCGTGGC 17 4799

BCLllA-4668 - CGCGTGTGTGGGGGGGAGCA 20 4800

BCLllA-4669 + CG G C A ATG GTTC CAG AT 17 4801

BCLllA-4670 - CGGCCACGCCACCGCCG 17 4802

BCLllA-4671 - CGGCCCGCCCCTCCCCC 17 4803

BCLllA-4672 + CGGCGAGACATGGTGGGCTG 20 4804

BCLllA-4673 + CGGCGGCGGCGGGCGGACGA 20 4805

BCLllA-4674 + CGGCGGCGGGCGGACGA 17 4806

BCLllA-4675 + CGGGGAGGGGGAGGTGC 17 4807

BCLllA-4676 + CGGGGCGGGGGGCTCCG 17 4808

BCLllA-4677 + CGGGGGAGGGGCGGGCCGAG 20 4809

BCLllA-4678 + CGTGGCCGGGAGAGAAGAAA 20 4810 BCLllA-4679 - CGTGTGTGGGGGGGAGC 17 4811

BCLllA-4680 + CGTTTG CTTAAGTG CTG 17 4812

BCLllA-4681 - CTAG AAG C AAAAG CG AG 17 4813

BCLllA-4682 - CTCCCCGCACTGGCCAT 17 4814

BCLllA-4683 - CTCGGCCCGCCCCTCCCCCG 20 4815

BCLllA-4684 + CTGAGCTGCAAGTTCAAGTG 20 4816

BCLllA-4685 + CTGCGAACTTGAACGTC 17 4817

BCLllA-4686 + CTGGACATGAAAAAGAGACC 20 4818

BCLllA-4687 + CTGTCTC AAAAGTG C ATACA 20 4819

BCLllA-4688 + CTTGAACGTCAGGAGTC 17 4820

BCLllA-4689 - CTTG AACTTG CAG CTCA 17 4821

BCLllA-4690 - CTTG AACTTG CAG CTC AGG G 20 4822

BCLllA-4691 + CTTGCGGCGAGACATGG 17 4823

BCLllA-4692 + GTTCACATCGGGAGAGC 17 4824

BCLllA-4693 + T A AT A CAAAGATGGCGC 17 4825

BCLllA-4694 + TAATTATTATTACTATTATT 20 4826

BCLllA-4695 + TACACGGCAATGGTTCCAGA 20 4827

BCLllA-4696 + TAGAAATAATACAAAGA 17 4828

BCLllA-4697 - TAG A AG C AAAAG CG AG G 17 4829

BCLllA-4698 - TAG AGTCCG CGTGTGTG 17 4830

BCLllA-4699 - TAGAGTCCGCGTGTGTGGGG 20 4831

BCLllA-4700 - TCCCGGCCACGCCACCGCCG 20 4832

BCLllA-4701 + TCCCGTTTG CTTAAGTG CTG 20 4833

BCLllA-4702 + TCCCTGCGAACTTGAACGTC 20 4834

BCLllA-4703 - TCGAGGTAAAAGAGATAAAG 20 4835

BCLllA-4704 - TCGGCCCGCCCCTCCCC 17 4836

BCLllA-4705 - TCGGCCCGCCCCTCCCCCGG 20 4837

BCLllA-4706 + TCTCAAAAGTGCATACA 17 4838

BCLllA-4707 - TCTC CTTCTTTCTA AC C 17 4839

BCLllA-4708 + TCTTTTACCTCGACTCT 17 4840

BCLllA-4709 - TG AACTTG CAG CTCAG G 17 4841

BCLllA-4710 - TGCGGCCACTGGTGAGCCCG 20 4842

BCLllA-4711 + TGCGGGGAGGGGGAGGTGCG 20 4843

BCLllA-4712 + TGCGGGGCGGGCGGCGG 17 4844

BCLllA-4713 + TGCGGGGCGGGCGGCGGCGG 20 4845

BCLllA-4714 - TG CTTA A A A A A A AG C C ATG A 20 4846

BCLllA-4715 + TGGCCAGTGCGGGGAGG 17 4847

BCLllA-4716 + TGGCCAGTGCGGGGAGGGGG 20 4848

BCLllA-4717 - TGGCCATTGGCTTGTCC 17 4849

BCLllA-4718 + TGGCCGGGAGAGAAGAA 17 4850

BCLllA-4719 + TGGGAGGAAAGGGTGGG 17 4851

BCLllA-4720 + TGGGGCCGCGGGCTCACCAG 20 4852 BCLllA-4721 + TGGTTCCAGATGGGATG 17 4853

BCLllA-4722 - TTAAAAAAAAGCCATGA 17 4854

BCLllA-4723 - TTAGAGTCCGCGTGTGTGGG 20 4855

BCLllA-4724 + TTATTATTACTATTATT 17 4856

BCLllA-4725 - TTATTTCTAATTTATTT 17 4857

BCLllA-4726 - TTATTTTG G ATGTCAAA 17 4858

BCLllA-4727 + TTCACATCGGGAGAGCC 17 4859

BCLllA-4728 + TTCCCGTTTG CTTAAGTG CT 20 4860

BCLllA-4729 + TTGAACGTCAGGAGTCTGGA 20 4861

BCLllA-4730 - TTG AACTTG CAG CTCAG 17 4862

BCLllA-4731 + TTGCTTGCGGCGAGACATGG 20 4863

BCLllA-4732 + TTGTGGGAGAGCCGTCA 17 4864

BCLllA-4733 - TTTTAG AGTCCG CGTGTGTG 20 4865

Table 10A provides exemplary targeting domains for knocking down expression of the BCL11A gene according to first tier parameters. The targeting domains are between 500bp upstream and 500bp downstream of transcription start site, good orthogonality, starts with G. 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 eiCas9 molecule to cause a steric block at the target region, e.g., between 500bp upstream and 500bp downstream of transcription start site to block transcription resulting in the repression of the BCL11A gene. Alternatively, any of the targeting domains in the table can be used with a S. aureus eiCas9 fused to a transcriptional repressor to decrease transcription and therefore downregulate gene expres

Table 10A

BCLllA-4744 + GTCCCTGCGAACTTGAACGT 20 4876

BCLllA-4745 + GTGACGTCCCTGCGAAC 17 4877

Table 10B provides exemplary targeting domains for knocking down expression of the BCLllA gene according to second tier parameters. The targeting domains are between 500bp upstream and 500bp downstream of transcription start site, good orthogonality and do not start with G. 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 eiCas9 molecule to cause a steric block at the target region, e.g., between 500bp upstream and 500bp downstream of transcription start site to block transcription resulting in the repression of the BCLllA gene. Alternatively, any of the targeting domains in the table can be used with a S. aureus eiCas9 fused to a transcriptional repressor to decrease transcription and therefore downregulate gene expression.

Table 10B

Table IOC provides exemplary targeting domains for knocking down expression of the BCLllA gene according to third tier parameters. The targeting domains are between 500bp upstream and 500bp downstream of transcription start site and start with G. 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 eiCas9 molecule to cause a steric block at the target region, e.g., between 500bp upstream and 500bp downstream of transcription start site to block transcription resulting in the repression of the BCL11A gene. Alternatively, any of the targeting domains in the table can be used with a S. aureus eiCas9 fused to a transcriptional repressor to decrease transcription and therefore downregulate gene expression.

Table IOC

BCLllA-4790 + GAGCAGGAGAGAAGGGG 17 4922

BCLllA-4791 + GAGCAGGAGAGAAGGGGAGG 20 4923

BCLllA-4792 + GAGCCGGGTTAGAAAGA 17 4924

BCLllA-4793 + G AG CTG C AAGTTC AAGT 17 4925

BCLllA-4794 + GAGGGAGAGAGAGAGAA 17 4926

BCLllA-4795 + GAGGGGCGGGCCGAGGG 17 4927

BCLllA-4796 + GAGGGGGAGGTGCGGGG 17 4928

BCLllA-4797 + GAGGGGGCGCTGGGGCC 17 4929

BCLllA-4798 - GAGGTAAAAGAGATAAA 17 4930

BCLllA-4799 - GAGTCCGCGTGTGTGGG 17 4931

BCLllA-4800 - GAGTCGAGGTAAAAGAGATA 20 4932

BCLllA-4801 + GATAGAGGGAGAGAGAGAGA 20 4933

BCLllA-4802 - GA I GAAGA I A I 1 1 I C I C 17 4934

BCLllA-4803 - G ATGTCAAAAGG CACTG 17 4935

BCLllA-4804 - GATGTGTGTCCATTGGT 17 4936

BCLllA-4805 + G CAATG GTTCC AG ATGG G AT 20 4937

BCLllA-4806 - G C ACTTG AACTTG CAG CTCA 20 4938

BCLllA-4807 - GCAGGACTAGAAGCAAAAGC 20 4939

BCLllA-4808 + GCAGGAGAGAAGGGGAG 17 4940

BCLllA-4809 + GCAGGGAAGATGAATTG 17 4941

BCLllA-4810 + GCAGGGAAGATGAATTGTGG 20 4942

BCLllA-4811 + GCAGGGCGAGCAGGAGAGAA 20 4943

BCLllA-4812 + GCAGGGGTGGGAGGAAAGGG 20 4944

BCLllA-4813 - GCA I 1 1 1 I AAA I 1 1 1 I C 17 4945

BCLllA-4814 + GCCAATGGCCAGTGCGGGGA 20 4946

BCLllA-4815 + GCCAGACGCGGCCCCCG 17 4947

BCLllA-4816 + GCCAGACGCGGCCCCCGGGG 20 4948

BCLllA-4817 + GCCCCCGGGGGAGGGGCGGG 20 4949

BCLllA-4818 + GCCGAGGGGAGGGGGCG 17 4950

BCLllA-4819 + GCCGCGGCGGTGGCGTGGCC 20 4951

BCLllA-4820 - GCCGCGTCTGGCGTCCG 17 4952

BCLllA-4821 + GCGAGACATGGTGGGCT 17 4953

BCLllA-4822 - G CG CAG G ACTAG AAG CA AAA 20 4954

BCLllA-4823 + GCGCAGGGAAG ATG A ATTGT 20 4955

BCLllA-4824 + GCGCCGCGGCGGTGGCGTGG 20 4956

BCLllA-4825 + GCGGACGCCAGACGCGGCCC 20 4957

BCLllA-4826 + GCGGCGAGACATGGTGGGCT 20 4958

BCLllA-4827 + GCGGCGGTGGCGTGGCC 17 4959

BCLllA-4828 + GCGGGGAGGGGGAGGTG 17 4960

BCLllA-4829 + GCGGGGCGGGGGGCTCC 17 4961

BCLllA-4830 + GCGTGGCCGGGAGAGAAGAA 20 4962

BCLllA-4831 - GCGTGTGTGGGGGGGAG 17 4963 BCLllA-4832 + GCTCACCAGTGG CCG CA 17 4964

BCLllA-4833 - GCTCGCTGCGGCCACTG 17 4965

BCLllA-4834 + GCTGGACATGAAAAAGAGAC 20 4966

BCLllA-4835 + GCTTGCGGCGAGACATG 17 4967

BCLllA-4836 - GGAAAAAACCCTCATCCCAT 20 4968

BCLllA-4837 + GGAAGGGGAAGCTCACACCA 20 4969

BCLllA-4838 + GGACAAGCCAATGGCCAGTG 20 4970

BCLllA-4839 + GGACATGAAAAAGAGAC 17 4971

BCLllA-4840 + GGACGCCAGACGCGGCCCCC 20 4972

BCLllA-4841 - G G A CTAG A AG C A A A AG C 17 4973

BCLllA-4842 - G G A CTAG A AG C A A A AG CG AG 20 4974

BCLllA-4843 + GGAGAGAAGAAAGGGGTGGC 20 4975

BCLllA-4844 + GGAGAGAAGGGGAGGAGGGA 20 4976

BCLllA-4845 + GGAGAGAGAGAGAAGAGAGA 20 4977

BCLllA-4846 + GGAGAGCCGGGTTAGAAAGA 20 4978

BCLllA-4847 + GGAGGGGCGGGCCGAGGGGA 20 4979

BCLllA-4848 + GGAGGGGGAGGTGCGGG 17 4980

BCLllA-4849 + GGAGGGGGAGGTGCGGGGCG 20 4981

BCLllA-4850 + GGCAGGGCGAGCAGGAGAGA 20 4982

BCLllA-4851 + GGCAGGGGTGGGAGGAAAGG 20 4983

BCLllA-4852 - GGCCGCGTCTGGCGTCC 17 4984

BCLllA-4853 + GGCGAGCAGGAGAGAAG 17 4985

BCLllA-4854 + GGCGAGCAGGAGAGAAGGGG 20 4986

BCLllA-4855 + GGCGCAGGGAAG ATG A ATTG 20 4987

BCLllA-4856 - G G CG CTCG CTG CGGCCACTG 20 4988

BCLllA-4857 + GGCGGCGGCGGCGGCGG 17 4989

BCLllA-4858 + GGCGGCGGCGGCGGCGGCGG 20 4990

BCLllA-4859 + GGCGGTGGCGTGGCCGG 17 4991

BCLllA-4860 + GGCGTGGCCGGGAGAGAAGA 20 4992

BCLllA-4861 + GGGAAGATGAATTGTGG 17 4993

BCLllA-4862 + GGGAGAGAAGAAAGGGGTGG 20 4994

BCLllA-4863 + GGGAGAGCCGGGTTAGA 17 4995

BCLllA-4864 + GGGAGAGCCGGGTTAGAAAG 20 4996

BCLllA-4865 + GGGAGGAAAGGGTGGGG 17 4997

BCLllA-4866 + GGGAGGGGCGGGCCGAG 17 4998

BCLllA-4867 + GGGAGGGGCGGGCCGAGGGG 20 4999

BCLllA-4868 + GGGAGGGGGAGGTGCGGGGC 20 5000

BCLllA-4869 + GGGCAGGGCGAGCAGGA 17 5001

BCLllA-4870 + GGGCAGGGCGAGCAGGAGAG 20 5002

BCLllA-4871 + GGGCCGAGGGGAGGGGGCGC 20 5003

BCLllA-4872 + GGGCGAGCAGGAGAGAA 17 5004

BCLllA-4873 + GGGCGAGCAGGAGAGAAGGG 20 5005 BCLllA-4874 + GGGGAGGGGCGGGCCGA 17 5006

BCLllA-4875 + GGGGAGGGGCGGGCCGAGGG 20 5007

BCLllA-4876 + GGGGAGGGGGAGGTGCGGGG 20 5008

BCLllA-4877 + GGGGAGGGGGCGCTGGGGCC 20 5009

BCLllA-4878 - GGGGCCGCGTCTGGCGTCCG 20 5010

BCLllA-4879 + GGGGCGGGCCGAGGGGA 17 5011

BCLllA-4880 + GGGGGAGGGGCGGGCCG 17 5012

BCLllA-4881 + GGGGGAGGTGCGGGGCG 17 5013

BCLllA-4882 - GGGGGCCGCGTCTGGCGTCC 20 5014

BCLllA-4883 + GGGGTGGCAGGGGTGGG 17 5015

BCLllA-4884 + GGGGTGGGAGGAAAGGG 17 5016

BCLllA-4885 + GGGGTGGGAGGAAAGGGTGG 20 5017

BCLllA-4886 + GGGTGGCAGGGGTGGGAGGA 20 5018

BCLllA-4887 + GGGTGGGAGGAAAGGGT 17 5019

BCLllA-4888 + GGGTGGGAGGAAAGGGTGGG 20 5020

BCLllA-4889 - GGTAAAAGAGATAAAGG 17 5021

BCLllA-4890 + GGTGCGGGGCGGGGGGCTCC 20 5022

BCLllA-4891 + GGTGGGAGGAAAGGGTG 17 5023

BCLllA-4892 + GGTGGGAGGAAAGGGTGGGG 20 5024

BCLllA-4893 + GGTTAGAAAGAAGGAGACTC 20 5025

BCLllA-4894 + GGTTTGCCTTGCTTGCG 17 5026

BCLllA-4895 - GTCGAGGTAAAAGAGATAAA 20 5027

BCLllA-4896 + GTGGCCGGGAGAGAAGA 17 5028

BCLllA-4897 + GTGGGAGGAAAGGGTGG 17 5029

Table 10D provides exemplary targeting domains for knocking down expression of the BCL11A gene according to forth tier parameters. The targeting domains are between 500bp upstream and 500bp downstream of transcription start site and do not start with G. 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 eiCas9 molecule to cause a steric block at the target region, e.g., between 500bp upstream and 500bp downstream of transcription start site to block transcription resulting in the repression of the BCL11A gene. Alternatively, any of the targeting domains in the table can be used with a S. aureus eiCas9 fused to a transcriptional repressor to decrease transcription and therefore downregulate gene expression.

Table 10D

DNA Target Site SEQ ID gRNA Name Targeting Domain

Strand Length NO

BCLllA-4898 + AAAAAAAAAAAAAAAAA 17 5030

BCLllA-4899 + AAAAAAAAAAAAAAAAAAAA 20 5031

BCLllA-4900 + AAAAAAAAAAAAAAAAAAAG 20 5032

BCLllA-4901 + AAAAAAAAAAAAAAAAAAGA 20 5033

BCLllA-4902 + AAAAAAAAAAAAAAAAG 17 5034

BCLllA-4903 + AAAAAAAAAAAAAAAAGAGG 20 5035

BCLllA-4904 + AAAAAAAAAAAAAAAGA 17 5036

BCLllA-4905 + A A A A A A A A A A AAA AG AG G G A 20 5037

BCLllA-4906 + A A A A A A A A A AAA AG AG G 17 5038

BCLllA-4907 + AAAAAAAAAAAAGAGGGAGA 20 5039

BCLllA-4908 + A A A A A A A A A A AG AG G G A 17 5040

BCLllA-4909 + AAAAAAAAAAGAGGGAGAGA 20 5041

BCLllA-4910 + AAAAAAAAAGAGGGAGA 17 5042

BCLllA-4911 + AAAAAAAAGAGGGAGAGAGA 20 5043

BCLllA-4912 + AAAAAAAGAGGGAGAGA 17 5044

BCLllA-4913 + AAAAAATGGCAAAAGCCCCC 20 5045

BCLllA-4914 - AAAAACCCTCATCCCAT 17 5046

BCLllA-4915 + AAAAAGAGGGAGAGAGA 17 5047

BCLllA-4916 + AAAAAGAGGGAGAGAGAGAG 20 5048

BCLllA-4917 + A A A AC ATG GGCAGGGCGAGC 20 5049

BCLllA-4918 - AAAACCCTCATCCCATC 17 5050

BCLllA-4919 - AAAAGCGAGGGGGAGAG 17 5051

BCLllA-4920 - AAACCCCAGCACTTAAGCAA 20 5052

BCLllA-4921 + AAAGAGGGAGAGAGAGAGAA 20 5053

BCLllA-4922 + AAAGGGGTGGCAGGGGT 17 5054

BCLllA-4923 + AAAGGGGTGGCAGGGGTGGG 20 5055

BCLllA-4924 + AAATAATAC AAAG ATG G CG C 20 5056

BCLllA-4925 + AAATGGCAAAAGCCCCC 17 5057

BCLllA-4926 + AACATGGGCAGGGCGAG 17 5058

BCLllA-4927 + AACATGGGCAGGGCGAGCAG 20 5059

BCLllA-4928 - AACCCCAGCACTTAAGCAAA 20 5060

BCLllA-4929 - AACCCGGCTCTCCCGAT 17 5061

BCLllA-4930 + AAGAAAGGGGTGGCAGGGGT 20 5062

BCLllA-4931 + AAGAGAGATAGAGGGAGAGA 20 5063

BCLllA-4932 + AAGAGGGAGAGAGAGAG 17 5064

BCLllA-4933 + AAGATGGCG CAGGGAAG 17 5065

BCLllA-4934 - AAGCAAAAGCGAGGGGGAGA 20 5066

BCLllA-4935 + AAG CCAATG GCCAGTG C 17 5067

BCLllA-4936 + AAGCCAATGGCCAGTGCGGG 20 5068

BCLllA-4937 - AATAATAATTATTAATAATC 20 5069 BCLllA-4938 + AATAATACAAAGATGGCGCA 20 5070

BCLllA-4939 - AATAATTATTAATAATC 17 5071

BCLllA-4940 + AATAATTATTATTACTATTA 20 5072

BCLllA-4941 + AATACAAAG ATG G CG C A 17 5073

BCLllA-4942 + AATGGCCAGTGCGGGGA 17 5074

BCLllA-4943 + AATTATTATTACTATTA 17 5075

BCLllA-4944 + AATTCCCGTTTGCTTAAGTG 20 5076

BCLllA-4945 + ACAAAGATGGCGCAGGGAAG 20 5077

BCLllA-4946 + ACAAGCCAATGGCCAGT 17 5078

BCLllA-4947 + ACAAGCCAATGG CCAGTG CG 20 5079

BCLllA-4948 + ACACACAAAACATGGGCAGG 20 5080

BCLllA-4949 + ACACACATCAGGGGCTGGAC 20 5081

BCLllA-4950 + ACAGAGACACACAAAAC 17 5082

BCLllA-4951 + ACATGGGCAGGGCGAGC 17 5083

BCLllA-4952 + ACATGGTGGGCTGCGGG 17 5084

BCLllA-4953 + ACCAATGGACACACATC 17 5085

BCLllA-4954 - ACCCC AG C ACTTAAG CAAAC 20 5086

BCLllA-4955 - ACCTCCGAGAGTCGAGGTAA 20 5087

BCLllA-4956 - ACGAGAAAAACCTCCGAGAG 20 5088

BCLllA-4957 + ACGCCAGACGCGGCCCC 17 5089

BCLllA-4958 + ACGCCAGACGCGGCCCCCGG 20 5090

BCLllA-4959 + ACGCGGCCCCCGGGGGAGGG 20 5091

BCLllA-4960 + ACGGCAATGGTTCCAGA 17 5092

BCLllA-4961 + ACGTCAGGAGTCTGGATGGA 20 5093

BCLllA-4962 - A CTAG A AG C A A A AG CG A 17 5094

BCLllA-4963 + ACTATTATTGGGTTACTTAC 20 5095

BCLllA-4964 - ACTCCTGACGTTCAAGTTCG 20 5096

BCLllA-4965 - A CTG ATG A AG ATATTTTCTC 20 5097

BCLllA-4966 + ACTTGAACGTCAGGAGT 17 5098

BCLllA-4967 - ACTTGAACTTGCAGCTC 17 5099

BCLllA-4968 - AGAAAAACCTCCGAGAG 17 5100

BCLllA-4969 + AGAAAGGGGTGGCAGGG 17 5101

BCLllA-4970 + AGAAGAAAGGGGTGGCAGGG 20 5102

BCLllA-4971 + AGAAGAGAGATAGAGGGAGA 20 5103

BCLllA-4972 - AGAAGCAAAAGCGAGGGGGA 20 5104

BCLllA-4973 + AGAAGGGGAGGAGGGAA 17 5105

BCLllA-4974 + AGACGCGGCCCCCGGGG 17 5106

BCLllA-4975 + AGAGAAGAAAGGGGTGG 17 5107

BCLllA-4976 + AGAGAAGAGAGATAGAGGGA 20 5108

BCLllA-4977 + AGAGAAGGGGAGGAGGG 17 5109

BCLllA-4978 + AGAGAAGGGGAGGAGGGAAG 20 5110

BCLllA-4979 + AGAGACACACAAAACATGGG 20 5111 BCLllA-4980 + AGAGAGAAGAGAGATAG 17 5112

BCLllA-4981 + AGAGAGAAGAGAGATAGAGG 20 5113

BCLllA-4982 + AGAGAGAGAAGAGAGATAGA 20 5114

BCLllA-4983 + AGAGAGAGAGAAGAGAGATA 20 5115

BCLllA-4984 + AGAGAGATAGAGGGAGA 17 5116

BCLllA-4985 + AGAGATAGAGGGAGAGA 17 5117

BCLllA-4986 + AGAGCCGGGTTAGAAAG 17 5118

BCLllA-4987 + AGAGGGAGAGAGAGAGA 17 5119

BCLllA-4988 - AGAGTCCGCGTGTGTGG 17 5120

BCLllA-4989 + AGATAGAGGGAGAGAGA 17 5121

BCLllA-4990 - AG C A A A AG CGAGGGGGA 17 5122

BCLllA-4991 - AGCAAAAGCGAGGGGGAGAG 20 5123

BCLllA-4992 + AGCAGGAGAGAAGGGGAGGA 20 5124

BCLllA-4993 + AGCCAATGGCCAGTGCG 17 5125

BCLllA-4994 + AGCCAATGGCCAGTGCGGGG 20 5126

BCLllA-4995 + AGGACAAGCCAATGGCCAGT 20 5127

BCLllA-4996 - AGGACTAGAAGCAAAAGCGA 20 5128

BCLllA-4997 + AGGAGAGAAGGGGAGGA 17 5129

BCLllA-4998 + AGGAGAGAAGGGGAGGAGGG 20 5130

BCLllA-4999 + AGGGAGAGAGAGAGAGAGAG 20 5131

BCLllA-5000 + AGGGCGAGCAGGAGAGA 17 5132

BCLllA-5001 + AGGGGAAGCTCACACCA 17 5133

BCLllA-5002 + AGGGGCGGGCCGAGGGG 17 5134

BCLllA-5003 + AG G G G CTG G AC ATG AAA 17 5135

BCLllA-5004 + AGGGGGAGGTGCGGGGC 17 5136

BCLllA-5005 + AGGGGTGGCAGGGGTGG 17 5137

BCLllA-5006 + AGGGGTGGGAGGAAAGG 17 5138

BCLllA-5007 + AGGGGTGGGAGGAAAGGGTG 20 5139

BCLllA-5008 - AGGTAAAAGAGATAAAG 17 5140

BCLllA-5009 - AGTCCGCGTGTGTGGGG 17 5141

BCLllA-5010 - AGTCGAGGTAAAAGAGATAA 20 5142

BCLllA-5011 + AGTGCGGGGAGGGGGAGGTG 20 5143

BCLllA-5012 + ATAATACAAAGATGGCG 17 5144

BCLllA-5013 - ATA ATC A CGAGAGCGCG 17 5145

BCLllA-5014 + ATACACGGCAATGGTTCCAG 20 5146

BCLllA-5015 + ATAGAGGGAGAGAGAGA 17 5147

BCLllA-5016 + ATC AG G G G CTG G AC ATG AAA 20 5148

BCLllA-5017 + ATCGGGAGAGCCGGGTTAGA 20 5149

BCLllA-5018 + ATCTCTTTTACCTCGACTCT 20 5150

BCLllA-5019 + ATGGCCAGTGCGGGGAG 17 5151

BCLllA-5020 + ATGGGCAGGGCGAGCAG 17 5152

BCLllA-5021 + ATG GTTC C AG ATG G G AT 17 5153 BCLllA-5022 + ATTATTGGGTTACTTAC 17 5154

BCLllA-5023 - ATTATTTCTAATTTATT 17 5155

BCLllA-5024 + ATTCCCGTTTGCTTAAGTGC 20 5156

BCLllA-5025 - A l 1 1 I AGAG I CCGCG I G I G I 20 5157

BCLllA-5026 - A l l l l I AAA I 1 1 1 I CAC 17 5158

BCLllA-5027 - A 1 1 1 1 1 CACGAGAAAAACC 1 20 5159

BCLllA-5028 + CAAAACATGGGCAGGGCGAG 20 5160

BCLllA-5029 - CAAAAGCGAGGGGGAGA 17 5161

BCLllA-5030 + CAAGCCAATGGCCAGTG 17 5162

BCLllA-5031 + CAATG G AC ACAC ATC AGG G G 20 5163

BCLllA-5032 + CAATGGCCAGTGCGGGG 17 5164

BCLllA-5033 + CAATGGCCAGTGCGGGGAGG 20 5165

BCLllA-5034 + CAATG GTTCC AG ATGG G 17 5166

BCLllA-5035 + CACAAAACATGGGCAGG 17 5167

BCLllA-5036 + CACACCAATGGACACACATC 20 5168

BCLllA-5037 + CACACGCGGACTCTAAA 17 5169

BCLllA-5038 + CACATCAGGGGCTGGAC 17 5170

BCLllA-5039 + CACCAATGGACACACAT 17 5171

BCLllA-5040 + CACGGCAATGGTTCCAG 17 5172

BCLllA-5041 - CA 1 A 1 AAGA 1 A 1 1 1 I C I 20 5173

BCLllA-5042 - CACTTG AACTTG CAG CT 17 5174

BCLllA-5043 - CACTTG AACTTG CAG CTC AG 20 5175

BCLllA-5044 - CAG G ACTAG A AG C A A A A 17 5176

BCLllA-5045 - CAGGACTAGAAGCAAAAGCG 20 5177

BCLllA-5046 + CAGGAGAGAAGGGGAGG 17 5178

BCLllA-5047 + CAGGGAAGATGAATTGT 17 5179

BCLllA-5048 + CAGGGCGAGCAGGAGAG 17 5180

BCLllA-5049 + CAGGGCGAGCAGGAGAGAAG 20 5181

BCLllA-5050 + CAGGGGTGGGAGGAAAGGGT 20 5182

BCLllA-5051 + CAGTGCGGGGAGGGGGAGGT 20 5183

BCLllA-5052 - CA I GCA I 1 1 1 I AAA I 1 1 1 I C 20 5184

BCLllA-5053 + CATGGGCAGGGCGAGCAGGA 20 5185

BCLllA-5054 - CATTTTAGAGTCCGCGTGTG 20 5186

BCLllA-5055 + CCAATGGCCAGTGCGGG 17 5187

BCLllA-5056 + CCAATGGCCAGTGCGGGGAG 20 5188

BCLllA-5057 + CCACACACGCGGACTCTAAA 20 5189

BCLllA-5058 + CCAGACGCGGCCCCCGG 17 5190

BCLllA-5059 + CCAGACGCGGCCCCCGGGGG 20 5191

BCLllA-5060 - CCAGCACTTAAGCAAAC 17 5192

BCLllA-5061 - CCATTG CCGTGTATG CACTT 20 5193

BCLllA-5062 - CCCAGCACTTAAGCAAA 17 5194

BCLllA-5063 - CCCCAGCACTTAAGCAA 17 5195 BCLllA-5064 + CCCCGGGGGAGGGGCGGGCC 20 5196

BCLllA-5065 - CCCCTCGGCCCGCCCCTCCC 20 5197

BCLllA-5066 + CCCGGGGGAGGGGCGGG 17 5198

BCLllA-5067 + CCCGGGGGAGGGGCGGGCCG 20 5199

BCLllA-5068 + CCCGTTTGCTTAAGTGC 17 5200

BCLllA-5069 - CCCTCGGCCCGCCCCTCCCC 20 5201

BCLllA-5070 + CCCTGCTCCCCCCCACACAC 20 5202

BCLllA-5071 + CCGAGGGGAGGGGGCGC 17 5203

BCLllA-5072 - CCG C ACTTG AACTTG CAG CT 20 5204

BCLllA-5073 + CCGCGGCGGTGGCGTGG 17 5205

BCLllA-5074 + CCGGGGGAGGGGCGGGCCGA 20 5206

BCLllA-5075 - CCTCGGCCCGCCCCTCCCCC 20 5207

BCLllA-5076 - CCTGACGTTCAAGTTCG 17 5208

BCLllA-5077 + CCTGAGCTGCAAGTTCAAGT 20 5209

BCLllA-5078 - CCTGATGTGTGTCCATTGGT 20 5210

BCLllA-5079 + CGAACTTGAACGTCAGGAGT 20 5211

BCLllA-5080 + CGAGACATGGTGGGCTG 17 5212

BCLllA-5081 + CGAGCAGGAGAGAAGGG 17 5213

BCLllA-5082 + CGAGCAGGAGAGAAGGGGAG 20 5214

BCLllA-5083 - CGAGGTAAAAGAGATAA 17 5215

BCLllA-5084 - CGAGGTAAAAGAGATAAAGG 20 5216

BCLllA-5085 - CG CACTTG AACTTG CAG CTC 20 5217

BCLllA-5086 + CGCAGGGAAGATGAATT 17 5218

BCLllA-5087 + CGCCAGACGCGGCCCCC 17 5219

BCLllA-5088 + CGCCGCGGCGGTGGCGTGGC 20 5220

BCLllA-5089 + CGCGGCGGTGGCGTGGC 17 5221

BCLllA-5090 + CGCGGCGGTGGCGTGGCCGG 20 5222

BCLllA-5091 + CGGACGCCAGACGCGGCCCC 20 5223

BCLllA-5092 + CG G C A ATG GTTC CAG ATG G G 20 5224

BCLllA-5093 + CGGCCCCCGGGGGAGGG 17 5225

BCLllA-5094 - CGGCCCGCCCCTCCCCC 17 5226

BCLllA-5095 + CG G CG AG AC ATG GTG G G CTG 20 5227

BCLllA-5096 + CGGCGGCGGCGGCGGCG 17 5228

BCLllA-5097 + CGGCGGCGGCGGCGGCGGCG 20 5229

BCLllA-5098 + CGGCGGTGGCGTGGCCGGGA 20 5230

BCLllA-5099 + CGGGCCGAGGGGAGGGGGCG 20 5231

BCLllA-5100 + CGGGCTCACCAGTGGCCGCA 20 5232

BCLllA-5101 + CGGGGAGGGGGAGGTGCGGG 20 5233

BCLllA-5102 + CGGGGGAGGGGCGGGCC 17 5234

BCLllA-5103 + CGGGGGAGGGGCGGGCCGAG 20 5235

BCLllA-5104 + CGGTGGCGTGGCCGGGA 17 5236

BCLllA-5105 + CGGTGGCGTGGCCGGGAGAG 20 5237 BCLllA-5106 - CTAG AAG CAAAAG CG AG 17 5238

BCLllA-5107 - CTAG AAG C AAAAG CG AG GG G 20 5239

BCLllA-5108 - CTCCTGACGTTCAAGTTCGC 20 5240

BCLllA-5109 - CTCGGCCCGCCCCTCCC 17 5241

BCLllA-5110 + CTCTTTTACCTCGACTC 17 5242

BCLllA-5111 - CTGACGTTCAAGTTCGC 17 5243

BCLllA-5112 + CTTGAACGTCAGGAGTCTGG 20 5244

BCLllA-5113 - CTTG AACTTG C AG CTC A 17 5245

BCLllA-5114 + CTTGCTTGCGGCGAGACATG 20 5246

BCLllA-5115 - TAATAATTATTAATAATCAC 20 5247

BCLllA-5116 + TAATACA AAG ATGG CG C 17 5248

BCLllA-5117 - TAATTATTAATAATCAC 17 5249

BCLllA-5118 + TACACGGCAATGGTTCCAGA 20 5250

BCLllA-5119 + TAGAAAGAAGGAGACTC 17 5251

BCLllA-5120 - TAG AAG CAAAAG CGAGG 17 5252

BCLllA-5121 - TAGAGTCCGCGTGTGTG 17 5253

BCLllA-5122 - TAGAGTCCGCGTGTGTGGGG 20 5254

BCLllA-5123 + TATCTCTTTTACCTCGACTC 20 5255

BCLllA-5124 + TATTATTGGGTTACTTACGC 20 5256

BCLllA-5125 + TATTGG GTTACTTACG C 17 5257

BCLllA-5126 + TCACACCAATGGACACACAT 20 5258

BCLllA-5127 - TCACGAGAAAAACCTCC 17 5259

BCLllA-5128 + TCAGGAGTCTGGATGGA 17 5260

BCLllA-5129 - TCATTTTAGAGTCCGCGTGT 20 5261

BCLllA-5130 + TCCCGTTTGCTTAAGTG 17 5262

BCLllA-5131 - TCCGAGAGTCGAGGTAA 17 5263

BCLllA-5132 - TCCGCGTGTGTGGGGGGGAG 20 5264

BCLllA-5133 - TCGAGGTAAAAGAGATA 17 5265

BCLllA-5134 - TCGAGGTAAAAGAGATAAAG 20 5266

BCLllA-5135 - TCGGCCCGCCCCTCCCC 17 5267

BCLllA-5136 - TCTAACCCGGCTCTCCCGAT 20 5268

BCLllA-5137 + TCTCGGAGGTTTTTCTC 17 5269

BCLllA-5138 + TCTTTTACCTCGACTCT 17 5270

BCLllA-5139 + TGACATCCAAAATAAAT 17 5271

BCLllA-5140 - 1 A 1 AAGA 1 A 1 1 1 I C I 17 5272

BCLllA-5141 - I GCA I 1 1 1 I AAA I 1 1 1 I CAC 20 5273

BCLllA-5142 + TGCGGGGAGGGGGAGGT 17 5274

BCLllA-5143 + TGCTCCCCCCCACACAC 17 5275

BCLllA-5144 + TGGACACACATCAGGGG 17 5276

BCLllA-5145 + TGGACAGAGACACACAAAAC 20 5277

BCLllA-5146 + TGGCAGGGGTGGGAGGA 17 5278

BCLllA-5147 + TGGCCAGTGCGGGGAGG 17 5279 BCLllA-5148 + TGGCCGGGAGAGAAGAA 17 5280

BCLllA-5149 + TGGCGCAGGGAAGATGAATT 20 5281

BCLllA-5150 + TGGCGTGGCCGGGAGAG 17 5282

BCLllA-5151 + TGGGAGGAAAGGGTGGG 17 5283

BCLllA-5152 + TGGGGTTTGCCTTGCTTGCG 20 5284

BCLllA-5153 - TGTATTATTTCTAATTTATT 20 5285

BCLllA-5154 - TTAATAATCACGAGAGCGCG 20 5286

BCLllA-5155 + TTAGAAAGAAGGAGACTCCA 20 5287

BCLllA-5156 - TTAGAGTCCGCGTGTGT 17 5288

BCLllA-5157 - TTAGAGTCCGCGTGTGTGGG 20 5289

BCLllA-5158 - TTG AACTTG C AG CTC AG 17 5290

BCLllA-5159 - TTG CCGTGTATG CACTT 17 5291

BCLllA-5160 - TTGGATGTCAAAAGGCACTG 20 5292

BCLllA-5161 - TTTAGAGTCCGCGTGTG 17 5293

BCLllA-5162 - TTTAGAGTCCGCGTGTGTGG 20 5294

BCLllA-5163 - TTTCACGAGAAAAACCT 17 5295

BCLllA-5164 - TTTTAGAGTCCGCGTGT 17 5296

BCLllA-5165 - TTTTAGAGTCCGCGTGTGTG 20 5297

BCLllA-5166 - TTTTCACGAGAAAAACCTCC 20 5298

BCLllA-5167 + TTTTGACATCCAAAATAAAT 20 5299

Table 11 provides exemplary targeting domains for knocking down expression of the BCL11A gene. The targeting domains are between 500bp upstream and 500bp downstream of transcription start site. 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 eiCas9 molecule to cause a steric block at the target region, e.g., between 500bp upstream and 500bp downstream of transcription start site to block transcription resulting in the repression of the BCL11A gene. Alternatively, any of the targeting domains in the table can be used with a N. meningitidis eiCas9 fused to a transcriptional repressor to decrease transcription and therefore downregulate gene expression.

Table 11

Table 12A provides exemplary targeting domains for knocking out the BCL11A gene selected according to the first tier parameters. The targeting domains bind within the first 500 bp of the coding sequence (e.g., within 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. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 12A

BCLllA-5346 - ACCAUGUCUCGCCGCAAGCA 20 5332

BCLllA-5347 + GAGCUCCAUGUGCAGAACGA 20 5333

BCLllA-5348 - UCACAGAUAAACUUCUGCAC 20 5334

BCLllA-5349 + CGUCAUCCUCUGGCGUGACC 20 5335

BCLllA-5350 - GGAGCUCUAAUCCCCACGCC 20 5336

BCLllA-5351 - UCCCGUGGAGGUUGGCAUCC 20 5337

BCLllA-5352 + AUUCCCGUUUGCU UAAGUGC 20 5338

BCLllA-5353 + CCCCCAAUGGGAAGUUCAUC 20 5339

BCLllA-5354 + GCUCCCAACGGGCCGUGGUC 20 5340

BCLllA-5355 + UUUCAUCUCGAUUGGUGAAG 20 5341

BCLllA-5356 - UGUUUAUCAACGUCAUCUAG 20 5342

BCLllA-5357 + AGAGCUCCAUGUGCAGAACG 20 5343

BCLllA-5358 - G A A A A A AG C A U C C A A U C C CG 20 5344

BCLllA-5359 + GCGAGACAUGGUGGGCUGCG 20 5345

BCLllA-5360 - CAGAUAAACUUCUGCACUGG 20 5346

BCLllA-5361 + CGGCGAGACAUGGUGGGCUG 20 5347

BCLllA-5362 + CUGCACUCAUCCCAGGCGUG 20 5348

BCLllA-5363 - UGAACCAGACCACGGCCCGU 20 5349

BCLllA-5364 - GCAUCCAAUCCCGUGGAGGU 20 5350

BCLllA-5365 + UGCUUGCGGCGAGACAUGGU 20 5351

BCLllA-5366 + UCAAGAGGCUCGGCUGUGGU 20 5352

BCLllA-5367 - AUCAUGACCUCCUCACCUGU 20 5353

Table 12B provides exemplary targeting domains for knocking out the BCL11A gene selected according to the second tier parameters. The targeting domains bind within the first 500 bp of the coding sequence (e.g., within 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. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 12B

BCLllA-5373 + U UCAUCAUCUGUAAGAA 17 5359

BCLllA-5374 - CGUUGGGAGCUCCAGAA 17 5360

BCLllA-5375 - UCCCCUCGUUCUGCACA 17 5361

BCLllA-5376 - GAUGAUGAACCAGACCA 17 5362

BCLllA-5377 + CUGGAUGCCAACCUCCA 17 5363

BCLllA-5378 - C AG G U AAA U G AG A AG C A 17 5364

BCLllA-5379 - UAAACUUCUGCACUGGA 17 5365

BCLllA-5380 + UUCAUCUCGAUUGGUGA 17 5366

BCLllA-5381 + CAU U UG U AG AAG AAAU A 17 5367

BCLllA-5382 - AGGAAUUUGCCCCAAAC 17 5368

BCLllA-5383 - CC AG C ACU U AAG CAAAC 17 5369

BCLllA-5384 + CUUCUGGAGCUCCCAAC 17 5370

BCLllA-5385 + CAUCUGGCACUGCCCAC 17 5371

BCLllA-5386 + UGGAUGCCAACCUCCAC 17 5372

BCLllA-5387 - CAGAUAAACUUCUGCAC 17 5373

BCLllA-5388 + UAUUCUGCACUCAUCCC 17 5374

BCLllA-5389 - CGUGGAGGUUGGCAUCC 17 5375

BCLllA-5390 - AAACAGGAACACAUAGC 17 5376

BCLllA-5391 - UGCAGAAUAUGCCCCGC 17 5377

BCLllA-5392 + AUGGUGGGCUGCGGGGC 17 5378

BCLllA-5393 + ACU UACAAAUACCCUGC 17 5379

BCLllA-5394 + UGUACAUGUGUAGCUGC 17 5380

BCLllA-5395 + GAGACAUGGUGGGCUGC 17 5381

BCLllA-5396 - GUGUUGUAUUAUUUUGC 17 5382

BCLllA-5397 + CCAAUGGGAAGUUCAUC 17 5383

BCLllA-5398 + AGGUCAUGAUCCCCUUC 17 5384

BCLllA-5399 + GUAAGAAUGGCUUCAAG 17 5385

BCLllA-5400 - GUUGGGAGCUCCAGAAG 17 5386

BCLllA-5401 + CAGCU UUUUCUAAGCAG 17 5387

BCLllA-5402 + UCCAUGUGCAGAACGAG 17 5388

BCLllA-2671 + CAGAACGAGGGGAGGAG 17 5389

BCLllA-5403 - AAACUUCUGCACUGGAG 17 5390

BCLllA-5404 + GCUCCAUGUGCAGAACG 17 5391

BCLllA-5405 - AAAAGCAUCCAAUCCCG 17 5392

BCLllA-5406 + CUUACAAAUACCCUGCG 17 5393

BCLllA-5407 + AUUGGUGAAGGGGAAGG 17 5394

BCLllA-5408 + ACUGCCCACAGGUGAGG 17 5395

BCLllA-4500 + GGGGCGGGCGGCGGCGG 17 5396

BCLllA-5409 + UGCGGGGCGGGCGGCGG 17 5397

BCLllA-5410 + GGCUGCGGGGCGGGCGG 17 5398

BCLllA-5411 + GUGGGCUGCGGGGCGGG 17 5399

BCLllA-5412 + AUGUGCAGAACGAGGGG 17 5400 BCLllA-5413 + CAUGGUGGGCUGCGGGG 17 5401

BCLllA-5414 + CUUGCGGCGAGACAUGG 17 5402

BCLllA-5415 - AUAAACUUCUGCACUGG 17 5403

BCLllA-5416 - AGCAUCCAAUCCCGUGG 17 5404

BCLllA-5417 - GAUGAACUUCCCAUUGG 17 5405

BCLllA-5418 - CAUGACCUCCUCACCUG 17 5406

BCLllA-5419 + AACUUACAAAUACCCUG 17 5407

BCLllA-5420 - CUGCUUAGAAAAAGCUG 17 5408

BCLllA-5421 + U UCAAGAGGCUCGGCUG 17 5409

BCLllA-5422 + CGAGACAUGGUGGGCUG 17 5410

BCLllA-5423 + CACUCAUCCCAGGCGUG 17 5411

BCLllA-5424 + GGCACUGCCCACAGGUG 17 5412

BCLllA-5425 - AGAUGAACUUCCCAUUG 17 5413

BCLllA-5426 + GGGGUUUGCCUUGCUUG 17 5414

BCLllA-5427 + CUAUGUGUUCCUGUUUG 17 5415

BCLllA-5428 + UAAGAAUGUCCCCCAAU 17 5416

BCLllA-5429 - CCAGAUGAACUUCCCAU 17 5417

BCLllA-5430 + GCCAACCUCCACGGGAU 17 5418

BCLllA-5431 + AUUAUUAUUACUAUUAU 17 5419

BCLllA-5432 - CUCUAAUCCCCACGCCU 17 5420

BCLllA-5433 + AAUGGCUUCAAGAGGCU 17 5421

BCLllA-5434 + GUACAUGUGUAGCUGCU 17 5422

BCLllA-5435 - ACCAGACCACGGCCCGU 17 5423

BCLllA-5436 + GCACUCAUCCCAGGCGU 17 5424

BCLllA-5437 + AGAGGCUCGGCUGUGGU 17 5425

BCLllA-5438 - CAGAUGAACUUCCCAUU 17 5426

BCLllA-5439 + UUAUUAUUACUAUUAUU 17 5427

BCLllA-5440 - CCAGACCACGGCCCGUU 17 5428

BCLllA-5441 + UGCUAUGUGUUCCUGUU 17 5429

BCLllA-5442 + GCUAUGUGUUCCUGU UU 17 5430

BCLllA-5443 - AACCCCAGCACU UAAGCAAA 20 5431

BCLllA-5444 + AAAAUAAGAAUGUCCCCCAA 20 5432

BCLllA-5445 - C ACAA ACG G AAAC AAU G CAA 20 5433

BCLllA-5446 + UGGUUCAUCAUCUGUAAGAA 20 5434

BCLllA-5447 - GCCCGUUGGGAGCUCCAGAA 20 5435

BCLllA-5448 - UCCUCCCCUCGUUCUGCACA 20 5436

BCLllA-5449 - ACAGAUGAUGAACCAGACCA 20 5437

BCLllA-5450 + GACCUGGAUGCCAACCUCCA 20 5438

BCLllA-5451 - UAGCAGGUAAAUGAGAAGCA 20 5439

BCLllA-5452 - AGUGCAGAAUAUGCCCCGCA 20 5440

BCLllA-5453 - GGCCCGUUGGGAGCUCCAGA 20 5441

BCLllA-5454 + AUCUCGAUUGGUGAAGGGGA 20 5442 BCLllA-5455 - AGAUAAACUUCUGCACUGGA 20 5443

BCLllA-5456 + UUUUUCAUCUCGAUUGGUGA 20 5444

BCLllA-5457 - UAGAGGAAUUUGCCCCAAAC 20 5445

BCLllA-5458 - ACCCCAGCACUUAAGCAAAC 20 5446

BCLllA-5459 + CCCCU UCUGGAGCUCCCAAC 20 5447

BCLllA-5460 + GUUCAUCUGGCACUGCCCAC 20 5448

BCLllA-5461 + ACCUGGAUGCCAACCUCCAC 20 5449

BCLllA-5462 + GCAUAUUCUGCACUCAUCCC 20 5450

BCLllA-5463 - CCCAAACAGGAACACAUAGC 20 5451

BCLllA-5464 - GAGUGCAGAAUAUGCCCCGC 20 5452

BCLllA-5465 + GACAUGGUGGGCUGCGGGGC 20 5453

BCLllA-5466 + UCAACUUACAAAUACCCUGC 20 5454

BCLllA-5467 + AGUUGUACAUGUGUAGCUGC 20 5455

BCLllA-5468 + GGCGAGACAUGGUGGGCUGC 20 5456

BCLllA-5469 - UUGGUGUUGUAU UAUUUUGC 20 5457

BCLllA-5470 + GAUAAACAAUCGUCAUCCUC 20 5458

BCLllA-5471 + AGGAGGUCAUGAUCCCCUUC 20 5459

BCLllA-5472 + UCUGUAAGAAUGGCUUCAAG 20 5460

BCLllA-5473 - CCCGUUGGGAGCUCCAGAAG 20 5461

BCLllA-5474 - UGGCAUCCAGGUCACGCCAG 20 5462

BCLllA-5475 + CCACAG CU U U U U CU AAG CAG 20 5463

BCLllA-5476 + AGCUCCAUGUGCAGAACGAG 20 5464

BCLllA-5477 + GUGCAGAACGAGGGGAGGAG 20 5465

BCLllA-5478 - GAUAAACUUCUGCACUGGAG 20 5466

BCLllA-5479 + CUGGAGCUCCCAACGGGCCG 20 5467

BCLllA-5480 + U UCUGCACUCAUCCCAGGCG 20 5468

BCLllA-5481 + CAACUUACAAAUACCCUGCG 20 5469

BCLllA-5482 + UCGAUUGGUGAAGGGGAAGG 20 5470

BCLllA-5483 + GGCACUGCCCACAGGUGAGG 20 5471

BCLllA-5484 + UGCGGGGCGGGCGGCGGCGG 20 5472

BCLllA-5485 + GGCUGCGGGGCGGGCGGCGG 20 5473

BCLllA-5486 + GUGGGCUGCGGGGCGGGCGG 20 5474

BCLllA-5487 + AUGGUGGGCUGCGGGGCGGG 20 5475

BCLllA-5488 + UCCAUGUGCAGAACGAGGGG 20 5476

BCLllA-5489 + AGACAUGGUGGGCUGCGGGG 20 5477

BCLllA-5490 + UUGCUUGCGGCGAGACAUGG 20 5478

BCLllA-5491 - AAAAGCAUCCAAUCCCGUGG 20 5479

BCLllA-5492 - CCAGAUGAACUUCCCAU UGG 20 5480

BCLllA-5493 - GAUCAUGACCUCCUCACCUG 20 5481

BCLllA-5494 + CUCAACUUACAAAUACCCUG 20 5482

BCLllA-5495 - CCUCUGCUUAGAAAAAGCUG 20 5483

BCLllA-5496 + GGCUUCAAGAGGCUCGGCUG 20 5484 BCLllA-5497 + UCCCGUU UGCUUAAGUGCUG 20 5485

BCLllA-5498 + UCUGGCACUGCCCACAGGUG 20 5486

BCLllA-5499 - GCCAGAUGAACUUCCCAUUG 20 5487

BCLllA-5500 + GCUGGGGUUUGCCU UGCUUG 20 5488

BCLllA-5501 + CUGCUAUGUGUUCCUGUUUG 20 5489

BCLllA-5502 + AAAUAAGAAUGUCCCCCAAU 20 5490

BCLllA-5503 - GUGCCAGAUGAACUUCCCAU 20 5491

BCLllA-5504 + GAUGCUUUUU UCAUCUCGAU 20 5492

BCLllA-5505 + GAUGCCAACCUCCACGGGAU 20 5493

BCLllA-5506 - GAGCUCUAAUCCCCACGCCU 20 5494

BCLllA-5507 + AAGAAUGGCUUCAAGAGGCU 20 5495

BCLllA-5508 + GUUGUACAUGUGUAGCUGCU 20 5496

BCLllA-5509 + UUCCCGU UUGCUUAAGUGCU 20 5497

BCLllA-5510 + UCUGCACUCAUCCCAGGCGU 20 5498

BCLllA-5511 - UGCCAGAUGAACUUCCCAUU 20 5499

BCLllA-5512 - G AACCAG ACCACGG CCCG U U 20 5500

BCLllA-5513 + ACCUGCUAUGUGUUCCUGUU 20 5501

BCLllA-5514 + CCUGCUAUGUGUUCCUGUUU 20 5502

Table 12C provides exemplary targeting domains for knocking out the BCL11A gene selected according to the third 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 able 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 12C

BCLllA-5524 + CUGGGUACUACGCCGAA 17 5512

BCLllA-5525 + UCUCCGAAGCUAAGGAA 17 5513

BCLllA-5526 + GGGGGCGUCGCCAGGAA 17 5514

BCLllA-5527 + U UGCUACCUGGCUGGAA 17 5515

BCLllA-5528 + CUGCACCUAGUCCUGAA 17 5516

BCLllA-5529 + AACCAUGCACUGGUGAA 17 5517

BCLllA-5530 + AUUUUCUCAGAACUUAA 17 5518

BCLllA-5531 + UAUUCUUAGCAGGUUAA 17 5519

BCLllA-5532 - GACGAUGGCACUGUUAA 17 5520

BCLllA-5533 + CGGUGGUGGACUAAACA 17 5521

BCLllA-5534 - GGCCGCGAUGCCCAACA 17 5522

BCLllA-5535 - UACUUAGAAAGCGAACA 17 5523

BCLllA-2969 - GCACCGGCGCAGCCACA 17 5524

BCLllA-2924 - CGAGGCCGAGGGCCACA 17 5525

BCLllA-5536 - CCCGAGUGCCUUUGACA 17 5526

BCLllA-5537 + CUUGAACUUGGCCACCA 17 5527

BCLllA-5538 - AAAAU U UG AAG CCCCCA 17 5528

BCLllA-5539 + CUGCAAUAUGAAUCCCA 17 5529

BCLllA-5540 - UAUGGAGCCUCCCGCCA 17 5530

BCLllA-5541 + CGGGUGAUGGGUGGCCA 17 5531

BCLllA-5542 + UCUCCUAGAGAAAUCCA 17 5532

BCLllA-5543 - UCCCAGCCACCUCUCCA 17 5533

BCLllA-5544 - CUCGGGGCGCAGCGGCA 17 5534

BCLllA-5545 - CGACGUCAUGCAGGGCA 17 5535

BCLllA-5546 + CUGCAUGACGUCGGGCA 17 5536

BCLllA-5547 - GACUUAGAGAGCUGGCA 17 5537

BCLllA-5548 - CUGCCCGACGUCAUGCA 17 5538

BCLllA-5549 + CUCGCUGAAGUGCUGCA 17 5539

BCLllA-5550 - AGCCAUUCACCAGUGCA 17 5540

BCLllA-5551 - CACGCACAGAACACUCA 17 5541

BCLllA-5552 + GUCGGACUUGACCGUCA 17 5542

BCLllA-5553 + ACCAACCCGCGGGGUCA 17 5543

BCLllA-5554 - AGGCCCAGCUCAAAAGA 17 5544

BCLllA-5555 - GCUUCCGGCCUGGCAGA 17 5545

BCLllA-5556 - CCUGGGGGCGGAAGAGA 17 5546

BCLllA-5557 + CUUGAUGCGCUUAGAGA 17 5547

BCLllA-5558 - GCUGACGGAGAGCGAGA 17 5548

BCLllA-5559 - GCGCAUCAAGCUCGAGA 17 5549

BCLllA-5560 - UCGGACCGCAUAGACGA 17 5550

BCLllA-5561 - ACGGUCAAGUCCGACGA 17 5551

BCLllA-5562 - CACCUGGCCGAGGCCGA 17 5552

BCLllA-5563 + GUCUCCGAAGCUAAGGA 17 5553 BCLllA-5564 + GGGGGGCGUCGCCAGGA 17 5554

BCLllA-5565 + AGGUUGGAGACAGAGGA 17 5555

BCLllA-5566 + GGGCGGAUUGCAGAGGA 17 5556

BCLllA-5567 + GGGGCUGGGAGGGAGGA 17 5557

BCLllA-5568 - CCGGGGAGCUGGACGGA 17 5558

BCLllA-5569 - GUGUGGCAGUUU UCGGA 17 5559

BCLllA-5570 + GGAUUGCAGAGGAGGGA 17 5560

BCLllA-5571 + UUGACCGGGGGCUGGGA 17 5561

BCLllA-5572 + UGGAGAGGUGGCUGGGA 17 5562

BCLllA-5573 - CCGCCCGGGGAGCUGGA 17 5563

BCLllA-5574 - GCGGCACGGGAAGUGGA 17 5564

BCLllA-5575 + GCCCAGGACCUGGUGGA 17 5565

BCLllA-5576 - CAAAUCGUCCCCCAUGA 17 5566

BCLllA-5577 + UCUGCACCUAGUCCUGA 17 5567

BCLllA-5578 - GGAGGAGGAGGAGCUGA 17 5568

BCLllA-5579 + CAAAGGCACUCGGGUGA 17 5569

BCLllA-5580 + GGCCCGGACCACUAAUA 17 5570

BCLllA-5581 + GCAGUAACCUUUGCAUA 17 5571

BCLllA-5582 - AGCGAGAGGGUGGACUA 17 5572

BCLllA-5583 + UGGAGUCUCCGAAGCUA 17 5573

BCLllA-5584 - GUUGAAUCCAAUGGCUA 17 5574

BCLllA-5585 + CACAGGUUGCACUUGUA 17 5575

BCLllA-5586 + AAUUUUCUCAGAACUUA 17 5576

BCLllA-5587 + UCGGUGGUGGACUAAAC 17 5577

BCLllA-5588 - ACCUGAUCCCGGAGAAC 17 5578

BCLllA-5589 - AGCACUCCUCGGAGAAC 17 5579

BCLllA-2979 - CACCGGCGCAGCCACAC 17 5580

BCLllA-2916 - CCGAGGCCGAGGGCCAC 17 5581

BCLllA-5590 + UGCACGCGUGGUCGCAC 17 5582

BCLllA-5591 - UCGGGGCGCAGCGGCAC 17 5583

BCLllA-5592 + CAAGAGAAACCAUGCAC 17 5584

BCLllA-5593 - GCAACCUGGUGGUGCAC 17 5585

BCLllA-5594 + GCAGCAGCUUUUUGGAC 17 5586

BCLllA-5595 + CAUGACUUGGACUUGAC 17 5587

BCLllA-5596 - ACCCGAGUGCCUUUGAC 17 5588

BCLllA-5597 - CAAAUUUCAGAGCAACC 17 5589

BCLllA-5598 - GCCAGCUCCCCGGAACC 17 5590

BCLllA-5599 + UGCGCCGGUGCACCACC 17 5591

BCLllA-5600 - GCAUAAGCGCGGCCACC 17 5592

BCLllA-5601 - CAGCGAGGCCU UCCACC 17 5593

BCLllA-5602 + GCU UCUCGCCCAGGACC 17 5594

BCLllA-5603 + AUGACUUGGACUUGACC 17 5595 BCLllA-5604 - AACCUGCUAAGAAUACC 17 5596

BCLllA-5605 + AAGGGCGGCUUGCUACC 17 5597

BCLllA-5606 - CGACCACGCGUGCACCC 17 5598

BCLllA-5607 - GAAAAU U UG AAG CCCCC 17 5599

BCLllA-5608 + CCAUCUCU UCCGCCCCC 17 5600

BCLllA-5609 - UCCUCCCUCCCAGCCCC 17 5601

BCLllA-5610 - GGAGUUCGACCUGCCCC 17 5602

BCLllA-5611 + CCUCCGUCCAGCUCCCC 17 5603

BCLllA-5612 - GGCCGCGGCUGCUCCCC 17 5604

BCLllA-5613 - AGCCCACCGCUGUCCCC 17 5605

BCLllA-5614 - GCUUCUCCACACCGCCC 17 5606

BCLllA-5615 + CCGAGGCCGACUCGCCC 17 5607

BCLllA-5616 + GCUUAUGCU UCUCGCCC 17 5608

BCLllA-5617 - AUUAGUGGUCCGGGCCC 17 5609

BCLllA-5618 - GGCGGAAGAGAUGGCCC 17 5610

BCLllA-5619 + UUGAGCUGGGCCUGCCC 17 5611

BCLllA-5620 - CUCCACCGCCAGCUCCC 17 5612

BCLllA-5621 + CCCUCCGUCCAGCUCCC 17 5613

BCLllA-5622 - UGGCCGCGGCUGCUCCC 17 5614

BCLllA-5623 - CUGCAACCAUUCCAGCC 17 5615

BCLllA-5624 - CGGCUUCGGGCUGAGCC 17 5616

BCLllA-5625 - CGCUUCUCCACACCGCC 17 5617

BCLllA-5626 - CCACCGCAUAGAGCGCC 17 5618

BCLllA-5627 + CCCGAGGCCGACUCGCC 17 5619

BCLllA-5628 + GGAGGGGGGGCGUCGCC 17 5620

BCLllA-5629 + AUAGGGCUGGGCCGGCC 17 5621

BCLllA-5630 - GAGAGAGGCUUCCGGCC 17 5622

BCLllA-5631 + UGUUGGGCAUCGCGGCC 17 5623

BCLllA-5632 + GGCCCUCGGCCUCGGCC 17 5624

BCLllA-5633 + CUGGGCCUGCCCGGGCC 17 5625

BCLllA-5634 - UAUUAGUGGUCCGGGCC 17 5626

BCLllA-5635 + GCU UCAGCUUGCUGGCC 17 5627

BCLllA-5636 + UCGGGUGAUGGGUGGCC 17 5628

BCLllA-5637 + UUUGAGCUGGGCCUGCC 17 5629

BCLllA-5638 + GGGAUCUUUGAGCUGCC 17 5630

BCLllA-5639 + GAAAGCGCCCUUCUGCC 17 5631

BCLllA-5640 + ACCAAGUCGCUGGUGCC 17 5632

BCLllA-5641 + UCUCUCGAUACUGAUCC 17 5633

BCLllA-5642 - CGACCCCAACCUGAUCC 17 5634

BCLllA-5643 + GGUGGCGCGCCGCCUCC 17 5635

BCLllA-5644 - CCGGCUACGCGGCCUCC 17 5636

BCLllA-5645 + CCUCGUCCCCGUUCUCC 17 5637 BCLllA-5646 - GGCCUUCCACCAGGUCC 17 5638

BCLllA-5647 - CCCCAUAU UAGUGGUCC 17 5639

BCLllA-5648 - UAGCAAGCCGCCCU UCC 17 5640

BCLllA-5649 + CGCUGGUGCCGGGUUCC 17 5641

BCLllA-5650 - UAGGAGACUUAGAGAGC 17 5642

BCLllA-5651 + GAAGGGGCUCAGCGAGC 17 5643

BCLllA-2886 - CACACCGCCCGGGGAGC 17 5644

BCLllA-5652 + GCCGGGUUCCGGGGAGC 17 5645

BCLllA-5653 + UCUGCCCUCU UUUGAGC 17 5646

BCLllA-5654 + CCUGGAGGCCGCGUAGC 17 5647

BCLllA-5655 + AUCCUGGUAUUCUUAGC 17 5648

BCLllA-5656 + AAGGGAUACCAACCCGC 17 5649

BCLllA-5657 - AAGUCCCCUGACCCCGC 17 5650

BCLllA-5658 + CGCCCGUGUGGCUGCGC 17 5651

BCLllA-5659 + UAUGCGGUCCGACUCGC 17 5652

BCLllA-5660 - CCACGAGAACAGCUCGC 17 5653

BCLllA-5661 - UACUCGCAGUGGCUCGC 17 5654

BCLllA-5662 + GCUGCCCACCAAGUCGC 17 5655

BCLllA-5663 - CACCGCUGUCCCCAGGC 17 5656

BCLllA-5664 + GCGCCCUUCUGCCAGGC 17 5657

BCLllA-5665 + GUGUUGGGCAUCGCGGC 17 5658

BCLllA-5666 + UAACCUUUGCAUAGGGC 17 5659

BCLllA-5667 - GUGGUCCGGGCCCGGGC 17 5660

BCLllA-5668 + CCUGCAUGACGUCGGGC 17 5661

BCLllA-5669 + UGGACUUGACCGGGGGC 17 5662

BCLllA-5670 + GCAUCGCGGCCGGGGGC 17 5663

BCLllA-5671 + U UUGCAUAGGGCUGGGC 17 5664

BCLllA-5672 + CUAGAGAAAUCCAUGGC 17 5665

BCLllA-5673 + GCGGCUUGCUACCUGGC 17 5666

BCLllA-5674 - AGACUUAGAGAGCUGGC 17 5667

BCLllA-5675 + UCCCAUGGAGAGGUGGC 17 5668

BCLllA-5676 - GACGAAGACUCGGUGGC 17 5669

BCLllA-5677 - CCUGCCCGACGUCAUGC 17 5670

BCLllA-5394 + UGUACAUGUGUAGCUGC 17 5671

BCLllA-5678 + GGACUUGAGCGCGCUGC 17 5672

BCLllA-5679 - GUCCAAAAAGCUGCUGC 17 5673

BCLllA-5680 + CACCAAGUCGCUGGUGC 17 5674

BCLllA-5681 + GUGGCGCU UCAGCUUGC 17 5675

BCLllA-5682 + CCCCGUUCUCCGGGAUC 17 5676

BCLllA-5683 + CCCUGUCAAAGGCACUC 17 5677

BCLllA-5684 - CCGGGCGAGUCGGCCUC 17 5678

BCLllA-5685 - CUGGACGGAGGGAUCUC 17 5679 BCLllA-5686 + ACACAUCUUGAGCUCUC 17 5680

BCLllA-5687 + UCCUCGUCCCCGUUCUC 17 5681

BCLllA-5688 + AUGCCCUGCAUGACGUC 17 5682

BCLllA-5689 + UACCAACCCGCGGGGUC 17 5683

BCLllA-5690 - GCCCCAUAU UAGUGGUC 17 5684

BCLllA-5691 + GGCAAAAGGCGAUUGUC 17 5685

BCLllA-5692 - CGGGUUGGUAUCCCU UC 17 5686

BCLllA-5693 - GUAUCGAGAGAGGCUUC 17 5687

BCLllA-5694 - GGGUGGACUACGGCUUC 17 5688

BCLllA-5695 + UCGCUGGUGCCGGGUUC 17 5689

BCLllA-5696 - CAGGCCCAGCUCAAAAG 17 5690

BCLllA-5697 + GUGAAGAACCUAGAAAG 17 5691

BCLllA-5698 + UUCUUAGCAGGUUAAAG 17 5692

BCLllA-3087 - CGAGGAAGAGGAAGAAG 17 5693

BCLllA-5699 + UGAUGCGCUUAGAGAAG 17 5694

BCLllA-3083 - GGAGGACGACGAGGAAG 17 5695

BCLllA-3089 - GGAAGAAGAGGAGGAAG 17 5696

BCLllA-3075 - CGGGGACGAGGAGGAAG 17 5697

BCLllA-2876 - CGCAGCGGCACGGGAAG 17 5698

BCLllA-5700 + GGUGGUGGACUAAACAG 17 5699

BCLllA-5701 + A A AG AG G U UGG AG ACAG 17 5700

BCLllA-5702 + GGCCGGCCUGGGGACAG 17 5701

BCLllA-5703 - AAAUUUGAAGCCCCCAG 17 5702

BCLllA-5704 - GGGAUCUCGGGGCGCAG 17 5703

BCLllA-5705 - AGAACGUGUACUCGCAG 17 5704

BCLllA-5706 + GGAGGGGCGGAUUGCAG 17 5705

BCLllA-5707 + CCAACCCGCGGGGUCAG 17 5706

BCLllA-5708 - AGGAUCAGUAUCGAGAG 17 5707

BCLllA-5709 - AGCUGACGGAGAGCGAG 17 5708

BCLllA-5710 + GGU UGGAGACAGAGGAG 17 5709

BCLllA-5711 + GGGCUGGGAGGGAGGAG 17 5710

BCLllA-5712 + GAUUGCAGAGGAGGGAG 17 5711

BCLllA-5713 + ACUAAACAGGGGGGGAG 17 5712

BCLllA-5714 + AUAUGAAUCCCAUGGAG 17 5713

BCLllA-5715 - AGCACGCCCCAUAUUAG 17 5714

BCLllA-5716 - CCUGAUCCCGGAGAACG 17 5715

BCLllA-3081 - GGAAGAGGAGGACGACG 17 5716

BCLllA-5717 + CGAGGAGUGCUCCGACG 17 5717

BCLllA-2837 - CCCGGAGAACGGGGACG 17 5718

BCLllA-5718 - GUGGCUCGCCGGCUACG 17 5719

BCLllA-5719 + UGACUUGGACUUGACCG 17 5720

BCLllA-5720 + GAAGGGAUACCAACCCG 17 5721 BCLllA-5721 - GAAGUCCCCUGACCCCG 17 5722

BCLllA-5722 + UUUGGACAGGCCCCCCG 17 5723

BCLllA-5723 - CUUCUCCACACCGCCCG 17 5724

BCLllA-5724 + CGAGGCCGACUCGCCCG 17 5725

BCLllA-2946 + CGCCCGGGGAGCAGCCG 17 5726

BCLllA-5725 - CCACCUGGCCGAGGCCG 17 5727

BCLllA-5726 + GUUGGGCAUCGCGGCCG 17 5728

BCLllA-5727 - GGCACUGUUAAUGGCCG 17 5729

BCLllA-5728 - GCGCGGCCACCUGGCCG 17 5730

BCLllA-5729 + CAAACUCCCGUUCUCCG 17 5731

BCLllA-5730 - CAGCGCGCUCAAGUCCG 17 5732

BCLllA-5731 + GCUGGUGCCGGGUUCCG 17 5733

BCLllA-5732 - GGCGAGAAGCAUAAGCG 17 5734

BCLllA-5733 - CAUGCAGCACU UCAGCG 17 5735

BCLllA-5734 + UGGCCUGGGUGCACGCG 17 5736

BCLllA-5735 + AGGGAUACCAACCCGCG 17 5737

BCLllA-5736 - CACGAGAACAGCUCGCG 17 5738

BCLllA-5737 + UGACGUCGGGCAGGGCG 17 5739

BCLllA-5738 - GAACAGCUCGCGGGGCG 17 5740

BCLllA-5739 - GGGCGCGGUCGUGGGCG 17 5741

BCLllA-5740 + CUCCGUGUUGGGCAUCG 17 5742

BCLllA-5741 - CGGGCGAGUCGGCCUCG 17 5743

BCLllA-5742 - ACCACGAGAACAGCUCG 17 5744

BCLllA-5743 - UGGACGGAGGGAUCUCG 17 5745

BCLllA-5744 + CCCGCGAGCUGU UCUCG 17 5746

BCLllA-5745 - CUCGCGGGGCGCGGUCG 17 5747

BCLllA-5746 + GUGGUGGACUAAACAGG 17 5748

BCLllA-5747 + CCUCGGCCUCGGCCAGG 17 5749

BCLllA-3090 - GGAAGAGGAAGAAGAGG 17 5750

BCLllA-3091 - AGAAGAGGAGGAAGAGG 17 5751

BCLllA-3088 - GGACGAGGAGGAAGAGG 17 5752

BCLllA-5748 + GAGGUUGGAGACAGAGG 17 5753

BCLllA-5749 + GGGGCGGAUUGCAGAGG 17 5754

BCLllA-5750 + UGAAUCCCAUGGAGAGG 17 5755

BCLllA-5751 + GGAGUGCUCCGACGAGG 17 5756

BCLllA-3066 - GGAGAACGGGGACGAGG 17 5757

BCLllA-3092 - AGAGGAGGAAGAGGAGG 17 5758

BCLllA-5752 + GUUGGAGACAGAGGAGG 17 5759

BCLllA-3093 - GGAGGAAGAGGAGGAGG 17 5760

BCLllA-5753 + AUUGCAGAGGAGGGAGG 17 5761

BCLllA-5754 + GGGGGCUGGGAGGGAGG 17 5762

BCLllA-5755 - CGGGCUGAGCCUGGAGG 17 5763 BCLllA-5756 - CCCGGGGAGCUGGACGG 17 5764

BCLllA-5757 + GACUUGGACUUGACCGG 17 5765

BCLllA-5758 + U UGGGCAUCGCGGCCGG 17 5766

BCLllA-5759 + CGGCCUGGGGACAGCGG 17 5767

BCLllA-5760 + U UCCGGGGAGCUGGCGG 17 5768

BCLllA-5761 + CCAGGCGCUCUAUGCGG 17 5769

BCLllA-5762 - UUGCGACGAAGACUCGG 17 5770

BCLllA-5763 - GGGCGAGUCGGCCUCGG 17 5771

BCLllA-5764 + UCCAAGUGAUGUCUCGG 17 5772

BCLllA-5765 + GGCGUCGCCAGGAAGGG 17 5773

BCLllA-5766 + UGGUGGACUAAACAGGG 17 5774

BCLllA-3076 - GACGGAGAGCGAGAGGG 17 5775

BCLllA-5767 + CGGAUUGCAGAGGAGGG 17 5776

BCLllA-5768 + UUGCAGAGGAGGGAGGG 17 5777

BCLllA-5769 + ACCGGGGGCUGGGAGGG 17 5778

BCLllA-5770 + CCGUCCAGCUCCCCGGG 17 5779

BCLllA-5771 + GAGAAAUCCAUGGCGGG 17 5780

BCLllA-5772 - GGCGAGUCGGCCUCGGG 17 5781

BCLllA-5773 + GGUGGACUAAACAGGGG 17 5782

BCLllA-5774 - U UUGAAGCCCCCAGGGG 17 5783

BCLllA-5775 + CUGGGAGGGAGGAGGGG 17 5784

BCLllA-5776 + UGCAGAGGAGGGAGGGG 17 5785

BCLllA-5777 - CAUAGAGCGCCUGGGGG 17 5786

BCLllA-5778 - AGCCCCCAGGGGUGGGG 17 5787

BCLllA-5779 + GGCACUCGGGUGAUGGG 17 5788

BCLllA-5780 + CUUGACCGGGGGCUGGG 17 5789

BCLllA-5781 + AACAGGGGGGGAGUGGG 17 5790

BCLllA-5782 + GGUACUACGCCGAAUGG 17 5791

BCLllA-5783 + CCUAGAGAAAUCCAUGG 17 5792

BCLllA-5784 + GGACUUGACCGUCAUGG 17 5793

BCLllA-5785 - AUUUCAGAGCAACCUGG 17 5794

BCLllA-5786 + UCUCGCCCAGGACCUGG 17 5795

BCLllA-5787 - CUUCGGGCUGAGCCUGG 17 5796

BCLllA-5788 - CCGCAUAGAGCGCCUGG 17 5797

BCLllA-5789 + AUCUUUGAGCUGCCUGG 17 5798

BCLllA-5790 + GGGUUCCGGGGAGCUGG 17 5799

BCLllA-5791 - AGCGGCACGGGAAGUGG 17 5800

BCLllA-5792 - CGCGCUCAAGUCCG UGG 17 5801

BCLllA-5793 + GCGAGCUGUUCUCGUGG 17 5802

BCLllA-5794 + GGCGCUCUAUGCGGUGG 17 5803

BCLllA-5795 + AAGUGAUGUCUCGGUGG 17 5804

BCLllA-5796 - CGGCACCAGCGACU UGG 17 5805 BCLllA-5797 + GGGUACUACGCCGAAUG 17 5806

BCLllA-5798 + CGGACUUGACCGUCAUG 17 5807

BCLllA-5799 + GCAUGUGCGUCUUCAUG 17 5808

BCLllA-5800 + CCCGGACCACUAAUAUG 17 5809

BCLllA-5801 + CCCCCAGGCGCUCUAUG 17 5810

BCLllA-5802 + CAGUGCCAUCGUCUAUG 17 5811

BCLllA-5803 - GACACUUGUGAGUACUG 17 5812

BCLllA-5804 + CGUCGCAAGUGUCCCUG 17 5813

BCLllA-5805 - ACCGCAUAGAGCGCCUG 17 5814

BCLllA-5806 + AGGGCUGGGCCGGCCUG 17 5815

BCLllA-5807 + AGGGGCUCAGCGAGCUG 17 5816

BCLllA-5808 - CCUUUGACAGGGUGCUG 17 5817

BCLllA-5809 - AAGUCAUGCGAGUUCUG 17 5818

BCLllA-5810 + AGGGCUUCUCGCCCGUG 17 5819

BCLllA-5811 + CAGCUCCCCGGGCGGUG 17 5820

BCLllA-5812 + AGGCGCUCUAUGCGGUG 17 5821

BCLllA-5813 - UGAAGCCCCCAGGGGUG 17 5822

BCLllA-5814 - AGAGAGCUCAAGAUGUG 17 5823

BCLllA-5815 + UCUCCGGGAUCAGGUUG 17 5824

BCLllA-5816 + UGGGUACUACGCCGAAU 17 5825

BCLllA-5817 + GGAGGCUCCAUAGCCAU 17 5826

BCLllA-5818 - CCCAGCCACCUCUCCAU 17 5827

BCLllA-5819 + UGCAGUAACCUU UGCAU 17 5828

BCLllA-5820 + UCGGACUUGACCGUCAU 17 5829

BCLllA-5821 + AAAGGCACUCGGGUGAU 17 5830

BCLllA-5822 + GCCCGGACCACUAAUAU 17 5831

BCLllA-5823 + GU UCUCGCUCUUGAACU 17 5832

BCLllA-5824 + ACCCUGUCAAAGGCACU 17 5833

BCLllA-5825 - ACCACCGAGACAUCACU 17 5834

BCLllA-5826 - CACUUGCGACGAAGACU 17 5835

BCLllA-5827 - ACCCGGCACCAGCGACU 17 5836

BCLllA-5828 - GGUAUCCCUUCAGGACU 17 5837

BCLllA-5829 + GCAGAACUCGCAUGACU 17 5838

BCLllA-5830 + AGUGUCCCUGUGGCCCU 17 5839

BCLllA-5831 - CACCGCAUAGAGCGCCU 17 5840

BCLllA-5832 + UAGGGCUGGGCCGGCCU 17 5841

BCLllA-5833 + CCUGUGGCCCUCGGCCU 17 5842

BCLllA-5834 - CCCGGGCGAGUCGGCCU 17 5843

BCLllA-5835 + CUUCAGCUUGCUGGCCU 17 5844

BCLllA-5836 - CUCGUCGGAGCACUCCU 17 5845

BCLllA-5837 - GCCUUCCACCAGGUCCU 17 5846

BCLllA-5838 + AAGGGGCUCAGCGAGCU 17 5847 BCLllA-5839 + CUGCCCUCUU UUGAGCU 17 5848

BCLllA-5840 + AACCUUUGCAUAGGGCU 17 5849

BCLllA-5841 + GGACUUGACCGGGGGCU 17 5850

BCLllA-5842 + CCCAUGGAGAGGUGGCU 17 5851

BCLllA-5434 + GUACAUGUGUAGCUGCU 17 5852

BCLllA-5843 - UCCAAAAAGCUGCUGCU 17 5853

BCLllA-5844 - GCUGGACGGAGGGAUCU 17 5854

BCLllA-5845 + CACAUCUUGAGCUCUCU 17 5855

BCLllA-5846 - CCGCCAUGGAUUUCUCU 17 5856

BCLllA-5847 + GGGUCCAAGUGAUGUCU 17 5857

BCLllA-5848 - GUCUCCAACCUCU UUCU 17 5858

BCLllA-5849 - CUCGGUGGCCGGCGAGU 17 5859

BCLllA-5850 - CUGCUCCCCGGGCGAGU 17 5860

BCLllA-5851 + CUAAACAGGGGGGGAGU 17 5861

BCLllA-5852 + CAUGCCCUGCAUGACGU 17 5862

BCLllA-5853 - GGCGCGGUCGUGGGCGU 17 5863

BCLllA-5854 - GCCUUU UGCCUCCUCGU 17 5864

BCLllA-5855 + GGUGGAGAGACCGUCGU 17 5865

BCLllA-5856 - UCGCGGGGCGCGGUCGU 17 5866

BCLllA-5857 + GU UCUCCGGGAUCAGGU 17 5867

BCLllA-5858 + AGAACCUAGAAAGAGGU 17 5868

BCLllA-5859 + GGCCUGGGGACAGCGGU 17 5869

BCLllA-5860 + CAGGCGCUCUAUGCGGU 17 5870

BCLllA-5861 - CCCCUGACCCCGCGGGU 17 5871

BCLllA-5862 - U UGAAGCCCCCAGGGGU 17 5872

BCLllA-5863 - GGCACCAGCGACU UGGU 17 5873

BCLllA-5864 - ACACUUGUGAGUACUGU 17 5874

BCLllA-5865 + GUACACGUUCUCCGUGU 17 5875

BCLllA-5866 + GCACAGGUUGCACUUGU 17 5876

BCLllA-5867 - CUUCACACACCCCCAU U 17 5877

BCLllA-5868 - GAUCCCU UCCUUAGCUU 17 5878

BCLllA-5869 - AGGGUGGACUACGGCUU 17 5879

BCLllA-5870 + UUCUCCGGGAUCAGGU U 17 5880

BCLllA-5871 + UACACGUUCUCCGUGUU 17 5881

BCLllA-5872 + GCCCAGCAGCAGCUUU U 17 5882

BCLllA-5873 - AGAUGUGUGGCAGUUU U 17 5883

BCLllA-5874 + UGCUCCGACGAGGAGGCAAA 20 5884

BCLllA-5875 + GGUAUUCUUAGCAGGUUAAA 20 5885

BCLllA-5876 - GGUGCUGCGGUUGAAUCCAA 20 5886

BCLllA-5877 - GCCGGCCCAGCCCUAUGCAA 20 5887

BCLllA-5878 + CAACCGCAGCACCCUG UCAA 20 5888

BCLllA-5879 - AGGCUUCCGGCCUGGCAGAA 20 5889 BCLllA-5880 + AGCUUGAUGCGCUUAGAGAA 20 5890

BCLllA-5881 - CCCAACCUGAUCCCGGAGAA 20 5891

BCLllA-5882 - UCGGAGCACUCCUCGGAGAA 20 5892

BCLllA-5883 + UCUCUGGGUACUACGCCGAA 20 5893

BCLllA-5884 + GAGUCUCCGAAGCUAAGGAA 20 5894

BCLllA-5885 + AGGGGGGGCGUCGCCAGGAA 20 5895

BCLllA-5886 + GGCUUGCUACCUGGCUGGAA 20 5896

BCLllA-5887 + AUUCUGCACCUAGUCCUGAA 20 5897

BCLllA-5888 + AGAAACCAUGCACUGGUGAA 20 5898

BCLllA-5889 + CAAAUUUUCUCAGAACU UAA 20 5899

BCLllA-5890 + UGGUAUUCUUAGCAGGUUAA 20 5900

BCLllA-5891 - AUAGACGAUGGCACUGU UAA 20 5901

BCLllA-5892 + UCUCGGUGGUGGACUAAACA 20 5902

BCLllA-5893 - CCCGGCCGCGAUGCCCAACA 20 5903

BCLllA-5894 - AUCUACUUAGAAAGCGAACA 20 5904

BCLllA-5895 - GGUGCACCGGCGCAGCCACA 20 5905

BCLllA-3377 - GGCCGAGGCCGAGGGCCACA 20 5906

BCLllA-5896 - UCACCCGAGUGCCU UUGACA 20 5907

BCLllA-5897 + GCUCUUGAACUUGGCCACCA 20 5908

BCLllA-5898 - G AG AAAAU U UG AAG CCCCCA 20 5909

BCLllA-5899 + UGUCUGCAAUAUGAAUCCCA 20 5910

BCLllA-5900 - GGCUAUGGAGCCUCCCGCCA 20 5911

BCLllA-5901 + ACUCGGGUGAUGGGUGGCCA 20 5912

BCLllA-5902 + AAGUCUCCUAGAGAAAUCCA 20 5913

BCLllA-5903 - CCUUCCCAGCCACCUCUCCA 20 5914

BCLllA-5904 - GAUCUCGGGGCGCAGCGGCA 20 5915

BCLllA-5905 - GCCCGACGUCAUGCAGGGCA 20 5916

BCLllA-5906 + GCCCUGCAUGACGUCGGGCA 20 5917

BCLllA-5907 - GGAGACUUAGAGAGCUGGCA 20 5918

BCLllA-5908 - GCCCUGCCCGACGUCAUGCA 20 5919

BCLllA-5909 + GGCCUCGCUGAAGUGCUGCA 20 5920

BCLllA-5910 - AACAGCCAUUCACCAGUGCA 20 5921

BCLllA-5911 - CAACACGCACAGAACACUCA 20 5922

BCLllA-5912 + GUCGUCGGACUUGACCGUCA 20 5923

BCLllA-5913 + GAUACCAACCCGCGGGGUCA 20 5924

BCLllA-5914 - GGCAGGCCCAGCUCAAAAGA 20 5925

BCLllA-5915 - GAGGCUUCCGGCCUGGCAGA 20 5926

BCLllA-5916 - GCGCCUGGGGGCGGAAGAGA 20 5927

BCLllA-5917 + GAGCUUGAUGCGCUUAGAGA 20 5928

BCLllA-5918 - GGAGCUGACGGAGAGCGAGA 20 5929

BCLllA-5919 - UAAGCGCAUCAAGCUCGAGA 20 5930

BCLllA-5920 - GAGUCGGACCGCAUAGACGA 20 5931 BCLllA-5921 - AUGACGGUCAAGUCCGACGA 20 5932

BCLllA-5922 - GGCCACCUGGCCGAGGCCGA 20 5933

BCLllA-5923 + GGAGUCUCCGAAGCUAAGGA 20 5934

BCLllA-5924 + GAGGGGGGGCGUCGCCAGGA 20 5935

BCLllA-5925 + AAGAGGUUGGAGACAGAGGA 20 5936

BCLllA-5926 + GAGGGGCGGAUUGCAGAGGA 20 5937

BCLllA-5927 + CCGGGGGCUGGGAGGGAGGA 20 5938

BCLllA-5928 - CGCCCGGGGAGCUGGACGGA 20 5939

BCLllA-5929 - GAUGUGUGGCAGUU UUCGGA 20 5940

BCLllA-5930 + GGCGGAUUGCAGAGGAGGGA 20 5941

BCLllA-5931 + GACUUGACCGGGGGCUGGGA 20 5942

BCLllA-5932 + CCAUGGAGAGGUGGCUGGGA 20 5943

BCLllA-5933 - ACACCGCCCGGGGAGCUGGA 20 5944

BCLllA-5934 - GCAGCGGCACGGGAAGUGGA 20 5945

BCLllA-5935 + CUCGCCCAGGACCUGGUGGA 20 5946

BCLllA-5936 - GCACAAAUCGUCCCCCAUGA 20 5947

BCLllA-5937 + CAUUCUGCACCUAGUCCUGA 20 5948

BCLllA-5938 - AGAGGAGGAGGAGGAGCUGA 20 5949

BCLllA-5939 + UGUCAAAGGCACUCGGGUGA 20 5950

BCLllA-5940 + CCGGGCCCGGACCACUAAUA 20 5951

BCLllA-5941 + GU UGCAGUAACCUUUGCAUA 20 5952

BCLllA-5942 - GAGAGCGAGAGGGUGGACUA 20 5953

BCLllA-5943 + GUCUGGAGUCUCCGAAGCUA 20 5954

BCLllA-5944 - GCGGU UGAAUCCAAUGGCUA 20 5955

BCLllA-5945 + UCGCACAGGUUGCACUUGUA 20 5956

BCLllA-5946 + UCAAAUUUUCUCAGAACUUA 20 5957

BCLllA-5947 + GUCUCGGUGGUGGACUAAAC 20 5958

BCLllA-5948 - CCAACCUGAUCCCGGAGAAC 20 5959

BCLllA-5949 - CGGAGCACUCCUCGGAGAAC 20 5960

BCLllA-5950 - GUGCACCGGCGCAGCCACAC 20 5961

BCLllA-5951 - UGGCCGAGGCCGAGGGCCAC 20 5962

BCLllA-5952 + GGGUGCACGCGUGGUCGCAC 20 5963

BCLllA-5953 - AUCUCGGGGCGCAGCGGCAC 20 5964

BCLllA-5954 + U UGCAAGAGAAACCAUGCAC 20 5965

BCLllA-5955 - AGAGCAACCUGGUGGUGCAC 20 5966

BCLllA-5956 + CCAGCAGCAGCUUUUUGGAC 20 5967

BCLllA-5957 + UCGCAUGACU UGGACU UGAC 20 5968

BCLllA-5958 - AUCACCCGAGUGCCUUUGAC 20 5969

BCLllA-5959 - GUUCAAAUUUCAGAGCAACC 20 5970

BCLllA-5960 - ACCGCCAGCUCCCCGGAACC 20 5971

BCLllA-5961 + GGCUGCGCCGGUGCACCACC 20 5972

BCLllA-5962 - GAAGCAUAAGCGCGGCCACC 20 5973 BCLllA-5963 - CUUCAGCGAGGCCUUCCACC 20 5974

BCLllA-5964 + UAUGCUUCUCGCCCAGGACC 20 5975

BCLllA-5965 + CGCAUGACUUGGACUUGACC 20 5976

BCLllA-5966 - U UUAACCUGCUAAGAAUACC 20 5977

BCLllA-5967 + AGGAAGGGCGGCUUGCUACC 20 5978

BCLllA-5968 - GUGCGACCACGCGUGCACCC 20 5979

BCLllA-5969 - UGAGAAAAUUUGAAGCCCCC 20 5980

BCLllA-5970 + GGGCCAUCUCUUCCGCCCCC 20 5981

BCLllA-5971 - CCCUCCUCCCUCCCAGCCCC 20 5982

BCLllA-5972 - GAAGGAGUUCGACCUGCCCC 20 5983

BCLllA-5973 + AUCCCUCCGUCCAGCUCCCC 20 5984

BCLllA-5974 - AAUGGCCGCGGCUGCUCCCC 20 5985

BCLllA-5975 - UCUAGCCCACCGCUGUCCCC 20 5986

BCLllA-5976 - UGCGCUUCUCCACACCGCCC 20 5987

BCLllA-5977 + CCCCCGAGGCCGACUCGCCC 20 5988

BCLllA-5978 + CGCGCUUAUGCUUCUCGCCC 20 5989

BCLllA-5979 - CAUAUUAGUGGUCCGGGCCC 20 5990

BCLllA-5980 - GGGGGCGGAAGAGAUGGCCC 20 5991

BCLllA-5981 + CUUUUGAGCUGGGCCUGCCC 20 5992

BCLllA-5982 - UCUCUCCACCGCCAGCUCCC 20 5993

BCLllA-5983 + GAUCCCUCCGUCCAGCUCCC 20 5994

BCLllA-5984 - UAAUGGCCGCGGCUGCUCCC 20 5995

BCLllA-5985 - U UACUGCAACCAUUCCAGCC 20 5996

BCLllA-5986 - CUACGGCU UCGGGCUGAGCC 20 5997

BCLllA-5987 - U UGCGCUUCUCCACACCGCC 20 5998

BCLllA-5988 - CCCCCACCGCAUAGAGCGCC 20 5999

BCLllA-5989 + CCCCCCGAGGCCGACUCGCC 20 6000

BCLllA-5990 + GAGGGAGGGGGGGCGUCGCC 20 6001

BCLllA-5991 + UGCAUAGGGCUGGGCCGGCC 20 6002

BCLllA-5992 - AUCGAGAGAGGCUUCCGGCC 20 6003

BCLllA-5993 + CCGUGUUGGGCAUCGCGGCC 20 6004

BCLllA-5994 + UGUGGCCCUCGGCCUCGGCC 20 6005

BCLllA-5995 + GAGCUGGGCCUGCCCGGGCC 20 6006

BCLllA-5996 - CCAUAUUAGUGGUCCGGGCC 20 6007

BCLllA-5997 + GGCGCUUCAGCUUGCUGGCC 20 6008

BCLllA-5998 + CACUCGGGUGAUGGGUGGCC 20 6009

BCLllA-5999 + UCUUUUGAGCUGGGCCUGCC 20 6010

BCLllA-6000 + GAAGGGAUCUUUGAGCUGCC 20 6011

BCLllA-6001 + GUGGAAAGCGCCCUUCUGCC 20 6012

BCLllA-6002 + CCCACCAAGUCGCUGGUGCC 20 6013

BCLllA-6003 + GCCUCUCUCGAUACUGAUCC 20 6014

BCLllA-6004 - GAACGACCCCAACCUGAUCC 20 6015 BCLllA-6005 + CGUGGUGGCGCGCCGCCUCC 20 6016

BCLllA-6006 - UCGCCGGCUACGCGGCCUCC 20 6017

BCLllA-6007 + CCUCCUCGUCCCCGUUCUCC 20 6018

BCLllA-6008 - CGAGGCCUUCCACCAGGUCC 20 6019

BCLllA-6009 - ACGCCCCAUAUUAGUGGUCC 20 6020

BCLllA-6010 - AGGUAGCAAGCCGCCCUUCC 20 6021

BCLllA-6011 + AGUCGCUGGUGCCGGGUUCC 20 6022

BCLllA-6012 - CUCUAGGAGACUUAGAGAGC 20 6023

BCLllA-6013 + AGAGAAGGGGCUCAGCGAGC 20 6024

BCLllA-6014 - CUCCACACCGCCCGGGGAGC 20 6025

BCLllA-6015 + GGUGCCGGGUUCCGGGGAGC 20 6026

BCLllA-6016 + GCGUCUGCCCUCUUUUGAGC 20 6027

BCLllA-6017 + CUGCCUGGAGGCCGCGUAGC 20 6028

BCLllA-6018 + CUGAUCCUGGUAUUCU UAGC 20 6029

BCLllA-6019 + CUGAAGGGAUACCAACCCGC 20 6030

BCLllA-6020 - CGGAAGUCCCCUGACCCCGC 20 6031

BCLllA-6021 + UCUCGCCCGUGUGGCUGCGC 20 6032

BCLllA-6022 + GUCUAUGCGGUCCGACUCGC 20 6033

BCLllA-6023 - CCACCACGAGAACAGCUCGC 20 6034

BCLllA-6024 - GUGUACUCGCAGUGGCUCGC 20 6035

BCLllA-6025 + GGCGCUGCCCACCAAGUCGC 20 6036

BCLllA-6026 - GCCCACCGCUGUCCCCAGGC 20 6037

BCLllA-6027 + AAAGCGCCCUUCUGCCAGGC 20 6038

BCLllA-6028 + UCCGUGUUGGGCAUCGCGGC 20 6039

BCLllA-6029 + CAGUAACCUUUGCAUAGGGC 20 6040

BCLllA-6030 - U UAGUGGUCCGGGCCCGGGC 20 6041

BCLllA-6031 + UGCCCUGCAUGACGUCGGGC 20 6042

BCLllA-6032 + ACUUGGACUUGACCGGGGGC 20 6043

BCLllA-6033 + UGGGCAUCGCGGCCGGGGGC 20 6044

BCLllA-6034 + ACCU UUGCAUAGGGCUGGGC 20 6045

BCLllA-6035 + CUCCUAGAGAAAUCCAUGGC 20 6046

BCLllA-6036 + AGGGCGGCUUGCUACCUGGC 20 6047

BCLllA-6037 - AGGAGACUUAGAGAGCUGGC 20 6048

BCLllA-6038 + GAAUCCCAUGGAGAGGUGGC 20 6049

BCLllA-6039 - UGCGACGAAGACUCGGUGGC 20 6050

BCLllA-6040 - CGCCCUGCCCGACGUCAUGC 20 6051

BCLllA-5467 + AGUUGUACAUGUGUAGCUGC 20 6052

BCLllA-6041 + CACGGACUUGAGCGCGCUGC 20 6053

BCLllA-6042 - CCUGUCCAAAAAGCUGCUGC 20 6054

BCLllA-6043 + GCCCACCAAGUCGCUGGUGC 20 6055

BCLllA-6044 + CAUGUGGCGCUUCAGCU UGC 20 6056

BCLllA-6045 + CGUCCCCGUUCUCCGGGAUC 20 6057 BCLllA-6046 + GCACCCUGUCAAAGGCACUC 20 6058

BCLllA-6047 - UCCCCGGGCGAGUCGGCCUC 20 6059

BCLllA-6048 - GAGCUGGACGGAGGGAUCUC 20 6060

BCLllA-6049 + GCCACACAUCUUGAGCUCUC 20 6061

BCLllA-6050 + UCCUCCUCGUCCCCGUUCUC 20 6062

BCLllA-6051 + ACCAUGCCCUGCAUGACGUC 20 6063

BCLllA-6052 + GGAUACCAACCCGCGGGGUC 20 6064

BCLllA-6053 - CACGCCCCAUAU UAGUGGUC 20 6065

BCLllA-6054 + GGAGGCAAAAGGCGAUUGUC 20 6066

BCLllA-6055 - CCGCGGGUUGGUAUCCCUUC 20 6067

BCLllA-6056 - UCAGUAUCGAGAGAGGCUUC 20 6068

BCLllA-6057 - AGAGGGUGGACUACGGCUUC 20 6069

BCLllA-6058 + AAGUCGCUGGUGCCGGGUUC 20 6070

BCLllA-6059 - GGGCAGGCCCAGCUCAAAAG 20 6071

BCLllA-6060 + UGUGUGAAGAACCUAGAAAG 20 6072

BCLllA-6061 + GUAUUCUUAGCAGGUUAAAG 20 6073

BCLllA-3449 - CGACGAGGAAGAGGAAGAAG 20 6074

BCLllA-6062 + GCUUGAUGCGCUUAGAGAAG 20 6075

BCLllA-3448 - AGAGGAGGACGACGAGGAAG 20 6076

BCLllA-3453 - AGAGGAAGAAGAGGAGGAAG 20 6077

BCLllA-3441 - GAACGGGGACGAGGAGGAAG 20 6078

BCLllA-3376 - GGGCGCAGCGGCACGGGAAG 20 6079

BCLllA-6063 + CUCGGUGGUGGACUAAACAG 20 6080

BCLllA-6064 + UAGAAAGAGGUUGGAGACAG 20 6081

BCLllA-6065 + CUGGGCCGGCCUGGGGACAG 20 6082

BCLllA-6066 - AGAAAAUUUGAAGCCCCCAG 20 6083

BCLllA-6067 - GGAGGGAUCUCGGGGCGCAG 20 6084

BCLllA-6068 - CGGAGAACGUGUACUCGCAG 20 6085

BCLllA-6069 + GGAGGAGGGGCGGAUUGCAG 20 6086

BCLllA-6070 + AUACCAACCCGCGGGGUCAG 20 6087

BCLllA-6071 - ACCAGGAUCAGUAUCGAGAG 20 6088

BCLllA-6072 - AGGAGCUGACGGAGAGCGAG 20 6089

BCLllA-6073 + AG AGG U UGG AGACAGAGGAG 20 6090

BCLllA-6074 + CGGGGGCUGGGAGGGAGGAG 20 6091

BCLllA-6075 + GCGGAUUGCAGAGGAGGGAG 20 6092

BCLllA-6076 + UGGACUAAACAGGGGGGGAG 20 6093

BCLllA-6077 + GCAAUAUGAAUCCCAUGGAG 20 6094

BCLllA-6078 - GGGAGCACGCCCCAUAU UAG 20 6095

BCLllA-6079 - CAACCUGAUCCCGGAGAACG 20 6096

BCLllA-3450 - GGAGGAAGAGGAGGACGACG 20 6097

BCLllA-6080 + CUCCGAGGAGUGCUCCGACG 20 6098

BCLllA-6081 - GAUCCCGGAGAACGGGGACG 20 6099 BCLllA-6082 - GCAGUGGCUCGCCGGCUACG 20 6100

BCLllA-6083 + GCAUGACUUGGACUUGACCG 20 6101

BCLllA-6084 + CCUGAAGGGAUACCAACCCG 20 6102

BCLllA-6085 - ACGGAAGUCCCCUGACCCCG 20 6103

BCLllA-6086 + CUUUUUGGACAGGCCCCCCG 20 6104

BCLllA-6087 - GCGCUUCUCCACACCGCCCG 20 6105

BCLllA-6088 + CCCCGAGGCCGACUCGCCCG 20 6106

BCLllA-6089 + ACUCGCCCGGGGAGCAGCCG 20 6107

BCLllA-6090 - CGGCCACCUGGCCGAGGCCG 20 6108

BCLllA-6091 + CGUGUUGGGCAUCGCGGCCG 20 6109

BCLllA-6092 - GAUGGCACUGUUAAUGGCCG 20 6110

BCLllA-6093 - UAAGCGCGGCCACCUGGCCG 20 6111

BCLllA-6094 + GCGCAAACUCCCGUUCUCCG 20 6112

BCLllA-6095 - CAG CAG CG CG C U CA AG U CCG 20 6113

BCLllA-6096 + GUCGCUGGUGCCGGGU UCCG 20 6114

BCLllA-6097 - CUGGGCGAGAAGCAUAAGCG 20 6115

BCLllA-6098 - CUCCAUGCAGCACUUCAGCG 20 6116

BCLllA-6099 + UGCUGGCCUGGGUGCACGCG 20 6117

BCLllA-6100 + UGAAGGGAUACCAACCCGCG 20 6118

BCLllA-6101 - CACCACGAGAACAGCUCGCG 20 6119

BCLllA-6102 + GCAUGACGUCGGGCAGGGCG 20 6120

BCLllA-6103 - CGAGAACAGCUCGCGGGGCG 20 6121

BCLllA-6104 - GCGGGGCGCGGUCGUGGGCG 20 6122

BCLllA-6105 + GUUCUCCGUGUUGGGCAUCG 20 6123

BCLllA-6106 - CCCCGGGCGAGUCGGCCUCG 20 6124

BCLllA-6107 - GCCACCACGAGAACAGCUCG 20 6125

BCLllA-6108 - AGCUGGACGGAGGGAUCUCG 20 6126

BCLllA-6109 + CGCCCCGCGAGCUGUUCUCG 20 6127

BCLllA-6110 - CAGCUCGCGGGGCGCGGUCG 20 6128

BCLllA-6111 + UCGGUGGUGGACUAAACAGG 20 6129

BCLllA-6112 + GGCCCUCGGCCUCGGCCAGG 20 6130

BCLllA-3451 - CGAGGAAGAGGAAGAAGAGG 20 6131

BCLllA-3452 - GGAAGAAGAGGAGGAAGAGG 20 6132

BCLllA-3445 - CGGGGACGAGGAGGAAGAGG 20 6133

BCLllA-6113 + AAAGAGGUUGGAGACAGAGG 20 6134

BCLllA-6114 + GGAGGGGCGGAUUGCAGAGG 20 6135

BCLllA-6115 + AUAUGAAUCCCAUGGAGAGG 20 6136

BCLllA-6116 + CGAGGAGUGCUCCGACGAGG 20 6137

BCLllA-3330 - CCCGGAGAACGGGGACGAGG 20 6138

BCLllA-3454 - AGAAGAGGAGGAAGAGGAGG 20 6139

BCLllA-6117 + GAGGUUGGAGACAGAGGAGG 20 6140

BCLllA-3455 - AGAGGAGGAAGAGGAGGAGG 20 6141 BCLllA-6118 + CGGAUUGCAGAGGAGGGAGG 20 6142

BCLllA-6119 + ACCGGGGGCUGGGAGGGAGG 20 6143

BCLllA-6120 - CUUCGGGCUGAGCCUGGAGG 20 6144

BCLllA-6121 - CCGCCCGGGGAGCUGGACGG 20 6145

BCLllA-6122 + CAUGACUUGGACUUGACCGG 20 6146

BCLllA-6123 + GUGUUGGGCAUCGCGGCCGG 20 6147

BCLllA-6124 + GGCCGGCCUGGGGACAGCGG 20 6148

BCLllA-6125 + GGGUUCCGGGGAGCUGGCGG 20 6149

BCLllA-6126 + CCCCCAGGCGCUCUAUGCGG 20 6150

BCLllA-6127 - CACUUGCGACGAAGACUCGG 20 6151

BCLllA-6128 - CCCGGGCGAGUCGGCCUCGG 20 6152

BCLllA-6129 + GGGUCCAAGUGAUGUCUCGG 20 6153

BCLllA-6130 + GGGGGCGUCGCCAGGAAGGG 20 6154

BCLllA-6131 + CGGUGGUGGACUAAACAGGG 20 6155

BCLllA-6132 - GCUGACGGAGAGCGAGAGGG 20 6156

BCLllA-6133 + GGGCGGAUUGCAGAGGAGGG 20 6157

BCLllA-6134 + GGAUUGCAGAGGAGGGAGGG 20 6158

BCLllA-6135 + UUGACCGGGGGCUGGGAGGG 20 6159

BCLllA-6136 + CCUCCGUCCAGCUCCCCGGG 20 6160

BCLllA-6137 + CUAGAGAAAUCCAUGGCGGG 20 6161

BCLllA-6138 - CCGGGCGAGUCGGCCUCGGG 20 6162

BCLllA-6139 + GGUGGUGGACUAAACAGGGG 20 6163

BCLllA-6140 - AAAUUUGAAGCCCCCAGGGG 20 6164

BCLllA-6141 + GGGCUGGGAGGGAGGAGGGG 20 6165

BCLllA-6142 + GAUUGCAGAGGAGGGAGGGG 20 6166

BCLllA-6143 - CCGCAUAGAGCGCCUGGGGG 20 6167

BCLllA-6144 - UGAAGCCCCCAGGGGUGGGG 20 6168

BCLllA-6145 + AAAGGCACUCGGGUGAUGGG 20 6169

BCLllA-6146 + GGACUUGACCGGGGGCUGGG 20 6170

BCLllA-6147 + CUAAACAGGGGGGGAGUGGG 20 6171

BCLllA-6148 + CUGGGUACUACGCCGAAUGG 20 6172

BCLllA-6149 + UCUCCUAGAGAAAUCCAUGG 20 6173

BCLllA-6150 + GUCGGACUUGACCGUCAUGG 20 6174

BCLllA-6151 - CAAAUUUCAGAGCAACCUGG 20 6175

BCLllA-6152 + GCUUCUCGCCCAGGACCUGG 20 6176

BCLllA-6153 - CGGCUUCGGGCUGAGCCUGG 20 6177

BCLllA-6154 - CCACCGCAUAGAGCGCCUGG 20 6178

BCLllA-6155 + GGGAUCUUUGAGCUGCCUGG 20 6179

BCLllA-6156 + GCCGGGU UCCGGGGAGCUGG 20 6180

BCLllA-6157 - CGCAGCGGCACGGGAAGUGG 20 6181

BCLllA-6158 - CAGCGCGCUCAAGUCCGUGG 20 6182

BCLllA-6159 + CCCGCGAGCUGUUCUCGUGG 20 6183 BCLllA-6160 + CCAGGCGCUCUAUGCGGUGG 20 6184

BCLllA-6161 + UCCAAGUGAUGUCUCGGUGG 20 6185

BCLllA-6162 - ACCCGGCACCAGCGACUUGG 20 6186

BCLllA-6163 + UCUGGGUACUACGCCGAAUG 20 6187

BCLllA-6164 + CGUCGGACU UGACCGUCAUG 20 6188

BCLllA-6165 + UGUGCAUGUGCGUCUUCAUG 20 6189

BCLllA-6166 + GGGCCCGGACCACUAAUAUG 20 6190

BCLllA-6167 + CCGCCCCCAGGCGCUCUAUG 20 6191

BCLllA-6168 + UAACAGUGCCAUCGUCUAUG 20 6192

BCLllA-6169 - AGCGACACUUGUGAGUACUG 20 6193

BCLllA-6170 + CUUCGUCGCAAGUGUCCCUG 20 6194

BCLllA-6171 - CCCACCGCAUAGAGCGCCUG 20 6195

BCLllA-6172 + CAUAGGGCUGGGCCGGCCUG 20 6196

BCLllA-6173 + AGAAGGGGCUCAGCGAGCUG 20 6197

BCLllA-6174 - GUGCCU UUGACAGGGUGCUG 20 6198

BCLllA-6175 - UCCAAGUCAUGCGAGUUCUG 20 6199

BCLllA-6176 + UGUAGGGCUUCUCGCCCGUG 20 6200

BCLllA-6177 + GUCCAGCUCCCCGGGCGGUG 20 6201

BCLllA-6178 + CCCAGGCGCUCUAUGCGGUG 20 6202

BCLllA-6179 - AUUUGAAGCCCCCAGGGGUG 20 6203

BCLllA-6180 - CCCAGAGAGCUCAAGAUGUG 20 6204

BCLllA-6181 + CGUUCUCCGGGAUCAGGUUG 20 6205

BCLllA-6182 + CUCUGGGUACUACGCCGAAU 20 6206

BCLllA-6183 + GCGGGAGGCUCCAUAGCCAU 20 6207

BCLllA-6184 - CUUCCCAGCCACCUCUCCAU 20 6208

BCLllA-6185 + GGUUGCAGUAACCUUUGCAU 20 6209

BCLllA-6186 + UCGUCGGACUUGACCGUCAU 20 6210

BCLllA-6187 + GUCAAAGGCACUCGGGUGAU 20 6211

BCLllA-6188 + CGGGCCCGGACCACUAAUAU 20 6212

BCLllA-6189 + GUCGUUCUCGCUCUUGAACU 20 6213

BCLllA-6190 + AGCACCCUGUCAAAGGCACU 20 6214

BCLllA-6191 - UCCACCACCGAGACAUCACU 20 6215

BCLllA-6192 - GGACACUUGCGACGAAGACU 20 6216

BCLllA-6193 - GGAACCCGGCACCAGCGACU 20 6217

BCLllA-6194 - GU UGGUAUCCCUUCAGGACU 20 6218

BCLllA-6195 + GCCGCAGAACUCGCAUGACU 20 6219

BCLllA-6196 + GCAAGUGUCCCUGUGGCCCU 20 6220

BCLllA-6197 - CCCCACCGCAUAGAGCGCCU 20 6221

BCLllA-6198 + GCAUAGGGCUGGGCCGGCCU 20 6222

BCLllA-6199 + GUCCCUGUGGCCCUCGGCCU 20 6223

BCLllA-6200 - CUCCCCGGGCGAGUCGGCCU 20 6224

BCLllA-6201 + GCGCUUCAGCUUGCUGGCCU 20 6225 BCLllA-6202 - CUCCUCGUCGGAGCACUCCU 20 6226

BCLllA-6203 - GAGGCCU UCCACCAGGUCCU 20 6227

BCLllA-6204 + GAGAAGGGGCUCAGCGAGCU 20 6228

BCLllA-6205 + CGUCUGCCCUCUUUUGAGCU 20 6229

BCLllA-6206 + AGUAACCUUUGCAUAGGGCU 20 6230

BCLllA-6207 + CUUGGACUUGACCGGGGGCU 20 6231

BCLllA-6208 + AAUCCCAUGGAGAGGUGGCU 20 6232

BCLllA-5508 + GUUGUACAUGUGUAGCUGCU 20 6233

BCLllA-6209 - CUGUCCAAAAAGCUGCUGCU 20 6234

BCLllA-6210 - GGAGCUGGACGGAGGGAUCU 20 6235

BCLllA-6211 + CCACACAUCUUGAGCUCUCU 20 6236

BCLllA-6212 - CUCCCGCCAUGGAU UUCUCU 20 6237

BCLllA-6213 + UGGGGGUCCAAGUGAUGUCU 20 6238

BCLllA-6214 - UCUGUCUCCAACCUCUUUCU 20 6239

BCLllA-6215 - AGACUCGGUGGCCGGCGAGU 20 6240

BCLllA-6216 - CGGCUGCUCCCCGGGCGAGU 20 6241

BCLllA-6217 + GGACUAAACAGGGGGGGAGU 20 6242

BCLllA-6218 + CACCAUGCCCUGCAUGACGU 20 6243

BCLllA-6219 - CGGGGCGCGGUCGUGGGCGU 20 6244

BCLllA-6220 - AUCGCCU UUUGCCUCCUCGU 20 6245

BCLllA-6221 + GGCGGUGGAGAGACCGUCGU 20 6246

BCLllA-6222 - AGCUCGCGGGGCGCGGUCGU 20 6247

BCLllA-6223 + CCCGUUCUCCGGGAUCAGGU 20 6248

BCLllA-6224 + UGAAGAACCUAGAAAGAGGU 20 6249

BCLllA-6225 + GCCGGCCUGGGGACAGCGGU 20 6250

BCLllA-6226 + CCCCAGGCGCUCUAUGCGGU 20 6251

BCLllA-6227 - AGUCCCCUGACCCCGCGGGU 20 6252

BCLllA-6228 - AAUUUGAAGCCCCCAGGGGU 20 6253

BCLllA-6229 - CCCGGCACCAGCGACUUGGU 20 6254

BCLllA-6230 - GCGACACU UGUGAGUACUGU 20 6255

BCLllA-6231 + CGAGUACACGUUCUCCGUGU 20 6256

BCLllA-6232 + GUCGCACAGGU UGCACU UGU 20 6257

BCLllA-6233 - GUUCUUCACACACCCCCAUU 20 6258

BCLllA-6234 - AAAGAUCCCUUCCUUAGCUU 20 6259

BCLllA-6235 - GAGAGGGUGGACUACGGCUU 20 6260

BCLllA-6236 + CCGUUCUCCGGGAUCAGGUU 20 6261

BCLllA-6237 + GAGUACACGUUCUCCGUGUU 20 6262

BCLllA-6238 + GCUGCCCAGCAGCAGCUUUU 20 6263

BCLllA-6239 - UCAAGAUGUGUGGCAGUUUU 20 6264

Table 12D provides targeting domains for knocking out the BCLllA gene by dual targeting (e.g., dual single strand cleavages). In an embodiment, dual targeting (e.g., dual nicking) 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. Exemplary nickase pairs including selecting a targeting domain from Group A and a second targeting domain from Group B, or including selecting a targeting domain from Group C and a second targeting domain from Group D. It is contemplated herein that in an embodiment a targeting domain of Group A can be combined with any of the targeting domains of Group B; in an embodiment a targeting domain of Group C can be combined with any of the targeting domains of Group D. Exemplary gRNA pairs to be used with S. pyogenes Cas9 are shown in Table 12D, e.g., BCL11A-5355 or BCL11A-5380 can be combined with BCL11 A-5321 or BCL11A-5416; or BCL11 A-5333, BCL11 A-5354, or BCL11 A-5329 can be combined with BCL11 A-5367 or BCLl lA-5341.

Table 12D

Table 13A provides exemplary targeting domains for knocking out the BCL11A gene selected according to the first tier parameters. The targeting domains bind within the first 500 bp of the coding sequence (e.g., within 500 bp downstream from the start codon), have a high level of orthogonality, and the 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 13A

BCLllA-6241 + GUGACCUGGAUGCCAACCUCCA 22 6266

BCLllA-6242 + CGUGACCUGGAUGCCAACCUCCA 23 6267

BCLllA-6243 + GCGUGACCUGGAUGCCAACCUCCA 24 6268

BCLllA-6244 + AUGCCAACCUCCACGGGA 18 6269

BCLllA-6245 + GAUGCCAACCUCCACGGGA 19 6270

BCLllA-6246 + GGAUGCCAACCUCCACGGGA 20 6271

BCLllA-6247 + UGGAUGCCAACCUCCACGGGA 21 6272

BCLllA-6248 + CUGGAUGCCAACCUCCACGGGA 22 6273

BCLllA-6249 + CCUGGAUGCCAACCUCCACGGGA 23 6274

BCLllA-6250 + ACCUGGAUGCCAACCUCCACGGGA 24 6275

BCLllA-6251 + GUCAUCCUCUGGCGUGAC 18 6276

BCLllA-6252 + CGUCAUCCUCUGGCGUGAC 19 6277

BCLllA-6253 + UCGUCAUCCUCUGGCGUGAC 20 6278

BCLllA-6254 + AUCGUCAUCCUCUGGCGUGAC 21 6279

BCLllA-6255 + AAUCGUCAUCCUCUGGCGUGAC 22 6280

BCLllA-6256 + CAAUCGUCAUCCUCUGGCGUGAC 23 6281

BCLllA-6257 + ACAAUCGUCAUCCUCUGGCGUGAC 24 6282

BCLllA-6258 + U UAUUGGGUUACUUACGC 18 6283

BCLllA-6259 + AUUAUUGGGUUACU UACGC 19 6284

BCLllA-6260 + UAUUAUUGGGUUACUUACGC 20 6285

BCLllA-6261 + CUAUUAUUGGGUUACUUACGC 21 6286

BCLllA-6262 + ACUAUUAUUGGGUUACUUACGC 22 6287

BCLllA-6263 + UACUAUUAUUGGGU UACUUACGC 23 6288

BCLllA-6264 + UUACUAUUAUUGGGUUACUUACGC 24 6289

BCLllA-6265 + UCCCGU UUGCUUAAGUGC 18 6290

BCLllA-6266 + UUCCCGU UUGCUUAAGUGC 19 6291

BCLllA-5352 + AUUCCCGUUUGCU UAAGUGC 20 6292

BCLllA-6267 + AAUUCCCGUU UGCUUAAGUGC 21 6293

BCLllA-6268 + GAAUUCCCGU UUGCUUAAGUGC 22 6294

BCLllA-6269 + AGAAUUCCCGUUUGCU UAAGUGC 23 6295

BCLllA-6270 + GAGAAUUCCCGU UUGCUUAAGUGC 24 6296

BCLllA-6271 + UUUGUGCUCGAUAAAAAU 18 6297

BCLllA-6272 + GUUUGUGCUCGAUAAAAAU 19 6298

BCLllA-6273 + CGUUUGUGCUCGAUAAAAAU 20 6299

BCLllA-6274 + CCGUUUGUGCUCGAUAAAAAU 21 6300

BCLllA-6275 + UCCGUUUGUGCUCGAUAAAAAU 22 6301

BCLllA-6276 + U UCCGUU UGUGCUCGAUAAAAAU 23 6302

BCLllA-6277 + U UUCCGU UUGUGCUCGAUAAAAAU 24 6303

BCLllA-6278 + UGCACUCAUCCCAGGCGU 18 6304

BCLllA-6279 + CUGCACUCAUCCCAGGCGU 19 6305

BCLllA-5510 + UCUGCACUCAUCCCAGGCGU 20 6306

BCLllA-6280 + U UCUGCACUCAUCCCAGGCGU 21 6307 BCLllA-6281 + AUUCUGCACUCAUCCCAGGCGU 22 6308

BCLllA-6282 + UAUUCUGCACUCAUCCCAGGCGU 23 6309

BCLllA-6283 + AUAUUCUGCACUCAUCCCAGGCGU 24 6310

BCLllA-6284 + GUCUGGUUCAUCAUCUGU 18 6311

BCLllA-6285 + GGUCUGGUUCAUCAUCUGU 19 6312

BCLllA-6286 + UGGUCUGGUUCAUCAUCUGU 20 6313

BCLllA-6287 + GUGGUCUGGUUCAUCAUCUGU 21 6314

BCLllA-6288 + CGUGGUCUGGUUCAUCAUCUGU 22 6315

BCLllA-6289 + CCGUGGUCUGGUUCAUCAUCUGU 23 6316

BCLllA-6290 + GCCGUGGUCUGGUUCAUCAUCUGU 24 6317

BCLllA-6291 - CCGUUGGGAGCUCCAGAA 18 6318

BCLllA-6292 - CCCGUUGGGAGCUCCAGAA 19 6319

BCLllA-5447 - GCCCGUUGGGAGCUCCAGAA 20 6320

BCLllA-6293 - GGCCCGUUGGGAGCUCCAGAA 21 6321

BCLllA-6294 - CGGCCCGUUGGGAGCUCCAGAA 22 6322

BCLllA-6295 - ACGGCCCGUUGGGAGCUCCAGAA 23 6323

BCLllA-6296 - CACGGCCCGUUGGGAGCUCCAGAA 24 6324

BCLllA-6297 - GGCAUCCAGGUCACGCCA 18 6325

BCLllA-6298 - UGGCAUCCAGGUCACGCCA 19 6326

BCLllA-6299 - UUGGCAUCCAGGUCACGCCA 20 6327

BCLllA-6300 - GUUGGCAUCCAGGUCACGCCA 21 6328

BCLllA-6301 - GGUUGGCAUCCAGGUCACGCCA 22 6329

BCLllA-6302 - AGGUUGGCAUCCAGGUCACGCCA 23 6330

BCLllA-6303 - GAGGUUGGCAUCCAGGUCACGCCA 24 6331

BCLllA-6304 - AACCCCAGCACUUAAGCAAAC 21 6332

BCLllA-6305 - AAACCCCAGCACUUAAGCAAAC 22 6333

BCLllA-6306 - CAAACCCCAGCACUUAAGCAAAC 23 6334

BCLllA-6307 - GCAAACCCCAGCACUUAAGCAAAC 24 6335

BCLllA-6308 - AGCUCUAAUCCCCACGCC 18 6336

BCLllA-6309 - GAGCUCUAAUCCCCACGCC 19 6337

BCLllA-5350 - GGAGCUCUAAUCCCCACGCC 20 6338

BCLllA-6310 - UGGAGCUCUAAUCCCCACGCC 21 6339

BCLllA-6311 - AUGGAGCUCUAAUCCCCACGCC 22 6340

BCLllA-6312 - CAUGGAGCUCUAAUCCCCACGCC 23 6341

BCLllA-6313 - ACAUGGAGCUCUAAUCCCCACGCC 24 6342

BCLllA-6314 - UUUAUCAACGUCAUCUAG 18 6343

BCLllA-6315 - GUUUAUCAACGUCAUCUAG 19 6344

BCLllA-5356 - UGUUUAUCAACGUCAUCUAG 20 6345

BCLllA-6316 - UUGUUUAUCAACGUCAUCUAG 21 6346

BCLllA-6317 - AUUGUUUAUCAACGUCAUCUAG 22 6347

BCLllA-6318 - GAUUGUUUAUCAACGUCAUCUAG 23 6348

BCLllA-6319 - CGAUUGUUUAUCAACGUCAUCUAG 24 6349 BCLllA-6320 - AGUGCAGAAUAUGCCCCG 18 6350

BCLllA-6321 - GAGUGCAGAAUAUGCCCCG 19 6351

BCLllA-6322 - UGAGUGCAGAAUAUGCCCCG 20 6352

BCLllA-6323 - AUGAGUGCAGAAUAUGCCCCG 21 6353

BCLllA-6324 - GAUGAGUGCAGAAUAUGCCCCG 22 6354

BCLllA-6325 - GGAUGAGUGCAGAAUAUGCCCCG 23 6355

BCLllA-6326 - GGGAUGAGUGCAGAAUAUGCCCCG 24 6356

BCLllA-6327 - CUAAUCCCCACGCCUGGG 18 6357

BCLllA-6328 - UCUAAUCCCCACGCCUGGG 19 6358

BCLllA-6329 - CUCUAAUCCCCACGCCUGGG 20 6359

BCLllA-6330 - GCUCUAAUCCCCACGCCUGGG 21 6360

BCLllA-6331 - AGCUCUAAUCCCCACGCCUGGG 22 6361

BCLllA-6332 - GAGCUCUAAUCCCCACGCCUGGG 23 6362

BCLllA-6333 - GGAGCUCUAAUCCCCACGCCUGGG 24 6363

BCLllA-6334 - CCACGCCUGGGAUGAGUG 18 6364

BCLllA-6335 - CCCACGCCUGGGAUGAGUG 19 6365

BCLllA-6336 - CCCCACGCCUGGGAUGAGUG 20 6366

BCLllA-6337 - UCCCCACGCCUGGGAUGAGUG 21 6367

BCLllA-6338 - AUCCCCACGCCUGGGAUGAGUG 22 6368

BCLllA-6339 - AAUCCCCACGCCUGGGAUGAGUG 23 6369

BCLllA-6340 - UAAUCCCCACGCCUGGGAUGAGUG 24 6370

BCLllA-6341 - CUCUGCUUAGAAAAAGCU 18 6371

BCLllA-6342 - CCUCUGCUUAGAAAAAGCU 19 6372

BCLllA-6343 - GCCUCUGCUUAGAAAAAGCU 20 6373

BCLllA-6344 - AGCCUCUGCU UAGAAAAAGCU 21 6374

BCLllA-6345 - CAGCCUCUGCU UAGAAAAAGCU 22 6375

BCLllA-6346 - GCAGCCUCUGCU UAGAAAAAGCU 23 6376

BCLllA-6347 - GGCAGCCUCUGCU UAGAAAAAGCU 24 6377

Table 13B provides exemplary targeting domains for knocking out the BCL11A gene selected according to the second tier parameters. The targeting domains bind within the first 500 bp of the coding sequence (e.g., within 500 bp downstream from the start codon), and the 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 13B

Strand Length NO

BCLllA-6348 + CCUGGAUGCCAACCUCCA 18 6378

BCLllA-6349 + ACCUGGAUGCCAACCUCCA 19 6379

BCLllA-5450 + GACCUGGAUGCCAACCUCCA 20 6380

BCLllA-6350 - CCCAG CAC U U AAG CAAAC 18 6381

BCLllA-6351 - CCCCAG CACU U AAG CAAAC 19 6382

BCLllA-5458 - ACCCCAGCACUUAAGCAAAC 20 6383

Table 13C provides exemplary targeting domains for knocking out the BCL11A gene selected according to the third tier parameters. The targeting domains bind within the first 500 bp of the coding sequence (e.g., within 500 bp downstream from the start codon), and the 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 13C

BCLllA-6370 + CGAUAAAAAUAAGAAUGUCCCCCA 24 6404

BCLllA-6371 + CCCCU UCUGGAGCUCCCA 18 6405

BCLllA-6372 + UCCCCUUCUGGAGCUCCCA 19 6406

BCLllA-6373 + AUCCCCUUCUGGAGCUCCCA 20 6407

BCLllA-6374 + GAUCCCCUUCUGGAGCUCCCA 21 6408

BCLllA-6375 + UGAUCCCCUUCUGGAGCUCCCA 22 6409

BCLllA-6376 + AUGAUCCCCUUCUGGAGCUCCCA 23 6410

BCLllA-6377 + CAUGAUCCCCUUCUGGAGCUCCCA 24 6411

BCLllA-6378 + UAGAGCUCCAUGUGCAGA 18 6412

BCLllA-6379 + UUAGAGCUCCAUGUGCAGA 19 6413

BCLllA-6380 + AUUAGAGCUCCAUGUGCAGA 20 6414

BCLllA-6381 + GAUUAGAGCUCCAUGUGCAGA 21 6415

BCLllA-6382 + GGAUUAGAGCUCCAUGUGCAGA 22 6416

BCLllA-6383 + GGGAUUAGAGCUCCAUGUGCAGA 23 6417

BCLllA-6384 + GGGGAUUAGAGCUCCAUGUGCAGA 24 6418

BCLllA-6385 + GCUCCAUGUGCAGAACGA 18 6419

BCLllA-6386 + AGCUCCAUGUGCAGAACGA 19 6420

BCLllA-5347 + GAGCUCCAUGUGCAGAACGA 20 6421

BCLllA-6387 + AGAGCUCCAUGUGCAGAACGA 21 6422

BCLllA-6388 + UAGAGCUCCAUGUGCAGAACGA 22 6423

BCLllA-6389 + UUAGAGCUCCAUGUGCAGAACGA 23 6424

BCLllA-6390 + AUUAGAGCUCCAUGUGCAGAACGA 24 6425

BCLllA-6391 + UUUCAUCUCGAUUGGUGA 18 6426

BCLllA-6392 + UUUUCAUCUCGAUUGGUGA 19 6427

BCLllA-5456 + UUUUUCAUCUCGAUUGGUGA 20 6428

BCLllA-6393 + UUUUUUCAUCUCGAUUGGUGA 21 6429

BCLllA-6394 + CUUUUUUCAUCUCGAU UGGUGA 22 6430

BCLllA-6395 + GCU UUUUUCAUCUCGAUUGGUGA 23 6431

BCLllA-6396 + UGCUUUUU UCAUCUCGAUUGGUGA 24 6432

BCLllA-6397 + GCAGAAGUUUAUCUGUGA 18 6433

BCLllA-6398 + UGCAGAAGUUUAUCUGUGA 19 6434

BCLllA-6399 + GUGCAGAAGUUUAUCUGUGA 20 6435

BCLllA-6400 + AGUGCAGAAGUUUAUCUGUGA 21 6436

BCLllA-6401 + CAGUGCAGAAGUUUAUCUGUGA 22 6437

BCLllA-6402 + CCAGUGCAGAAGUUUAUCUGUGA 23 6438

BCLllA-6403 + UCCAGUGCAGAAGUUUAUCUGUGA 24 6439

BCLllA-6404 + GAGCUCCAUGUGCAGAAC 18 6440

BCLllA-6405 + AGAGCUCCAUGUGCAGAAC 19 6441

BCLllA-6406 + UAGAGCUCCAUGUGCAGAAC 20 6442

BCLllA-6407 + U UAGAGCUCCAUGUGCAGAAC 21 6443

BCLllA-6408 + AUUAGAGCUCCAUGUGCAGAAC 22 6444

BCLllA-6409 + GAUUAGAGCUCCAUGUGCAGAAC 23 6445 BCLllA-6410 + GGAUUAGAGCUCCAUGUGCAGAAC 24 6446

BCLllA-6411 + UAUUAUUGGGUUACUUAC 18 6447

BCLllA-6412 + CUAUUAUUGGGUUACUUAC 19 6448

BCLllA-6413 + ACUAUUAUUGGGUUACUUAC 20 6449

BCLllA-6414 + UACUAUUAUUGGGU UACUUAC 21 6450

BCLllA-6415 + U UACUAUUAUUGGGUUACUUAC 22 6451

BCLllA-6416 + AUUACUAUUAUUGGGUUACUUAC 23 6452

BCLllA-6417 + UAUUACUAUUAUUGGGUUACUUAC 24 6453

BCLllA-6418 + ACCUGGAUGCCAACCUCC 18 6454

BCLllA-6419 + GACCUGGAUGCCAACCUCC 19 6455

BCLllA-6420 + UGACCUGGAUGCCAACCUCC 20 6456

BCLllA-6421 + GUGACCUGGAUGCCAACCUCC 21 6457

BCLllA-6422 + CGUGACCUGGAUGCCAACCUCC 22 6458

BCLllA-6423 + GCGUGACCUGGAUGCCAACCUCC 23 6459

BCLllA-6424 + GGCGUGACCUGGAUGCCAACCUCC 24 6460

BCLllA-6425 + UCUGCACUCAUCCCAGGC 18 6461

BCLllA-6426 + U UCUGCACUCAUCCCAGGC 19 6462

BCLllA-6427 + AUUCUGCACUCAUCCCAGGC 20 6463

BCLllA-6428 + UAUUCUGCACUCAUCCCAGGC 21 6464

BCLllA-6429 + AUAUUCUGCACUCAUCCCAGGC 22 6465

BCLllA-6430 + CAUAUUCUGCACUCAUCCCAGGC 23 6466

BCLllA-6431 + GCAUAUUCUGCACUCAUCCCAGGC 24 6467

BCLllA-6432 + GAGGUCAUGAUCCCCUUC 18 6468

BCLllA-6433 + GGAGGUCAUGAUCCCCU UC 19 6469

BCLllA-5471 + AGGAGGUCAUGAUCCCCUUC 20 6470

BCLllA-6434 + GAGGAGGUCAUGAUCCCCUUC 21 6471

BCLllA-6435 + UGAGGAGGUCAUGAUCCCCUUC 22 6472

BCLllA-6436 + GUGAGGAGGUCAUGAUCCCCU UC 23 6473

BCLllA-6437 + GGUGAGGAGGUCAUGAUCCCCUUC 24 6474

BCLllA-6438 + AUCUGUAAGAAUGGCUUC 18 6475

BCLllA-6439 + CAUCUGUAAGAAUGGCUUC 19 6476

BCLllA-6440 + UCAUCUGUAAGAAUGGCUUC 20 6477

BCLllA-6441 + AUCAUCUGUAAGAAUGGCUUC 21 6478

BCLllA-6442 + CAUCAUCUGUAAGAAUGGCUUC 22 6479

BCLllA-6443 + UCAUCAUCUGUAAGAAUGGCUUC 23 6480

BCLllA-6444 + UUCAUCAUCUGUAAGAAUGGCUUC 24 6481

BCLllA-6445 + UCAUCUCGAU UGGUGAAG 18 6482

BCLllA-6446 + UUCAUCUCGAUUGGUGAAG 19 6483

BCLllA-5355 + UUUCAUCUCGAUUGGUGAAG 20 6484

BCLllA-6447 + UUUUCAUCUCGAUUGGUGAAG 21 6485

BCLllA-6448 + UUUUUCAUCUCGAUUGGUGAAG 22 6486

BCLllA-6449 + UUUUUUCAUCUCGAUUGGUGAAG 23 6487 BCLllA-6450 + CUUUUUUCAUCUCGAU UGGUGAAG 24 6488

BCLllA-6451 + UCCACAGCU UUUUCUAAG 18 6489

BCLllA-6452 + AUCCACAGCUUUUUCUAAG 19 6490

BCLllA-6453 + UAUCCACAGCUUUUUCUAAG 20 6491

BCLllA-6454 + UUAUCCACAGCUUUUUCUAAG 21 6492

BCLllA-6455 + CUUAUCCACAGCUUUU UCUAAG 22 6493

BCLllA-6456 + GCUUAUCCACAGCUUU UUCUAAG 23 6494

BCLllA-6457 + GGCU UAUCCACAGCUUUUUCUAAG 24 6495

BCLllA-6458 + AUCUGGCACUGCCCACAG 18 6496

BCLllA-6459 + CAUCUGGCACUGCCCACAG 19 6497

BCLllA-6460 + UCAUCUGGCACUGCCCACAG 20 6498

BCLllA-6461 + UUCAUCUGGCACUGCCCACAG 21 6499

BCLllA-6462 + GUUCAUCUGGCACUGCCCACAG 22 6500

BCLllA-6463 + AGUUCAUCUGGCACUGCCCACAG 23 6501

BCLllA-6464 + AAGUUCAUCUGGCACUGCCCACAG 24 6502

BCLllA-6465 + CUCCAUGUGCAGAACGAG 18 6503

BCLllA-6466 + GCUCCAUGUGCAGAACGAG 19 6504

BCLllA-5476 + AGCUCCAUGUGCAGAACGAG 20 6505

BCLllA-6467 + GAGCUCCAUGUGCAGAACGAG 21 6506

BCLllA-6468 + AGAGCUCCAUGUGCAGAACGAG 22 6507

BCLllA-6469 + UAGAGCUCCAUGUGCAGAACGAG 23 6508

BCLllA-6470 + U UAGAGCUCCAUGUGCAGAACGAG 24 6509

BCLllA-6471 + UGUGCAGAACGAGGGGAG 18 6510

BCLllA-6472 + AUGUGCAGAACGAGGGGAG 19 6511

BCLllA-6473 + CAUGUGCAGAACGAGGGGAG 20 6512

BCLllA-6474 + CCAUGUGCAGAACGAGGGGAG 21 6513

BCLllA-6475 + UCCAUGUGCAGAACGAGGGGAG 22 6514

BCLllA-6476 + CUCCAUGUGCAGAACGAGGGGAG 23 6515

BCLllA-6477 + GCUCCAUGUGCAGAACGAGGGGAG 24 6516

BCLllA-6478 + AGCUCCAUGUGCAGAACG 18 6517

BCLllA-6479 + GAGCUCCAUGUGCAGAACG 19 6518

BCLllA-5357 + AGAGCUCCAUGUGCAGAACG 20 6519

BCLllA-6480 + UAGAGCUCCAUGUGCAGAACG 21 6520

BCLllA-6481 + U UAGAGCUCCAUGUGCAGAACG 22 6521

BCLllA-6482 + AUUAGAGCUCCAUGUGCAGAACG 23 6522

BCLllA-6483 + GAUUAGAGCUCCAUGUGCAGAACG 24 6523

BCLllA-6484 + CUGCACUCAUCCCAGGCG 18 6524

BCLllA-6485 + UCUGCACUCAUCCCAGGCG 19 6525

BCLllA-5480 + U UCUGCACUCAUCCCAGGCG 20 6526

BCLllA-6486 + AUUCUGCACUCAUCCCAGGCG 21 6527

BCLllA-6487 + UAUUCUGCACUCAUCCCAGGCG 22 6528

BCLllA-6488 + AUAUUCUGCACUCAUCCCAGGCG 23 6529 BCLllA-6489 + CAUAUUCUGCACUCAUCCCAGGCG 24 6530

BCLllA-6490 + GGGUUUGCCUUGCUUGCG 18 6531

BCLllA-6491 + GGGGUUUGCCUUGCUUGCG 19 6532

BCLllA-6492 + UGGGGUUUGCCUUGCUUGCG 20 6533

BCLllA-6493 + CUGGGGUUUGCCUUGCUUGCG 21 6534

BCLllA-6494 + GCUGGGGUUUGCCU UGCUUGCG 22 6535

BCLllA-6495 + UGCUGGGGUU UGCCUUGCUUGCG 23 6536

BCLllA-6496 + GUGCUGGGGUUUGCCU UGCUUGCG 24 6537

BCLllA-6497 + CCAUGUGCAGAACGAGGG 18 6538

BCLllA-6498 + UCCAUGUGCAGAACGAGGG 19 6539

BCLllA-6499 + CUCCAUGUGCAGAACGAGGG 20 6540

BCLllA-6500 + GCUCCAUGUGCAGAACGAGGG 21 6541

BCLllA-6501 + AGCUCCAUGUGCAGAACGAGGG 22 6542

BCLllA-6502 + GAGCUCCAUGUGCAGAACGAGGG 23 6543

BCLllA-6503 + AGAGCUCCAUGUGCAGAACGAGGG 24 6544

BCLllA-6504 + GACAUGGUGGGCUGCGGG 18 6545

BCLllA-6505 + AGACAUGGUGGGCUGCGGG 19 6546

BCLllA-6506 + GAGACAUGGUGGGCUGCGGG 20 6547

BCLllA-6507 + CGAGACAUGGUGGGCUGCGGG 21 6548

BCLllA-6508 + GCGAGACAUGGUGGGCUGCGGG 22 6549

BCLllA-6509 + GGCGAGACAUGGUGGGCUGCGGG 23 6550

BCLllA-6510 + CGGCGAGACAUGGUGGGCUGCGGG 24 6551

BCLllA-6511 + CAUGUGCAGAACGAGGGG 18 6552

BCLllA-6512 + CCAUGUGCAGAACGAGGGG 19 6553

BCLllA-5488 + UCCAUGUGCAGAACGAGGGG 20 6554

BCLllA-6513 + CUCCAUGUGCAGAACGAGGGG 21 6555

BCLllA-6514 + GCUCCAUGUGCAGAACGAGGGG 22 6556

BCLllA-6515 + AGCUCCAUGUGCAGAACGAGGGG 23 6557

BCLllA-6516 + GAGCUCCAUGUGCAGAACGAGGGG 24 6558

BCLllA-6517 + CAAGAGGCUCGGCUGUGG 18 6559

BCLllA-6518 + UCAAGAGGCUCGGCUGUGG 19 6560

BCLllA-6519 + UUCAAGAGGCUCGGCUGUGG 20 6561

BCLllA-6520 + CUUCAAGAGGCUCGGCUGUGG 21 6562

BCLllA-6521 + GCU UCAAGAGGCUCGGCUGUGG 22 6563

BCLllA-6522 + GGCU UCAAGAGGCUCGGCUGUGG 23 6564

BCLllA-6523 + UGGCUUCAAGAGGCUCGGCUGUGG 24 6565

BCLllA-6524 + UGCUUGCGGCGAGACAUG 18 6566

BCLllA-6525 + U UGCUUGCGGCGAGACAUG 19 6567

BCLllA-6526 + CUUGCUUGCGGCGAGACAUG 20 6568

BCLllA-6527 + CCUUGCU UGCGGCGAGACAUG 21 6569

BCLllA-6528 + GCCUUGCUUGCGGCGAGACAUG 22 6570

BCLllA-6529 + UGCCU UGCUUGCGGCGAGACAUG 23 6571 BCLllA-6530 + UUGCCUUGCUUGCGGCGAGACAUG 24 6572

BCLllA-6531 + CAACUUACAAAUACCCUG 18 6573

BCLllA-6532 + UCAACUUACAAAUACCCUG 19 6574

BCLllA-5494 + CUCAACUUACAAAUACCCUG 20 6575

BCLllA-6533 + GCUCAACUUACAAAUACCCUG 21 6576

BCLllA-6534 + GGCUCAACUUACAAAUACCCUG 22 6577

BCLllA-6535 + AGGCUCAACUUACAAAUACCCUG 23 6578

BCLllA-6536 + AAGGCUCAACUUACAAAUACCCUG 24 6579

BCLllA-6537 + GU UGUACAUGUGUAGCUG 18 6580

BCLllA-6538 + AGUUGUACAUGUGUAGCUG 19 6581

BCLllA-6539 + AAGUUGUACAUGUGUAGCUG 20 6582

BCLllA-6540 + CAAGUUGUACAUGUGUAGCUG 21 6583

BCLllA-6541 + GCAAGUUGUACAUGUGUAGCUG 22 6584

BCLllA-6542 + UGCAAGUUGUACAUGUGUAGCUG 23 6585

BCLllA-6543 + UUGCAAGUUGUACAUGUGUAGCUG 24 6586

BCLllA-6544 + GCGAGACAUGGUGGGCUG 18 6587

BCLllA-6545 + GGCGAGACAUGGUGGGCUG 19 6588

BCLllA-5361 + CGGCGAGACAUGGUGGGCUG 20 6589

BCLllA-6546 + GCGGCGAGACAUGGUGGGCUG 21 6590

BCLllA-6547 + UGCGGCGAGACAUGGUGGGCUG 22 6591

BCLllA-6548 + U UGCGGCGAGACAUGGUGGGCUG 23 6592

BCLllA-6549 + CUUGCGGCGAGACAUGGUGGGCUG 24 6593

BCLllA-6550 + U UCCCGUUUGCU UAAGUG 18 6594

BCLllA-6551 + AUUCCCGU UUGCUUAAGUG 19 6595

BCLllA-6552 + AAUUCCCGUUUGCUUAAGUG 20 6596

BCLllA-6553 + GAAUUCCCGU UUGCUUAAGUG 21 6597

BCLllA-6554 + AGAAUUCCCGUUUGCU UAAGUG 22 6598

BCLllA-6555 + GAGAAUUCCCGUUUGCUUAAGUG 23 6599

BCLllA-6556 + CGAGAAUUCCCGUUUGCUUAAGUG 24 6600

BCLllA-6557 + GGAGAGGCCCCUCCAGUG 18 6601

BCLllA-6558 + AGGAGAGGCCCCUCCAGUG 19 6602

BCLllA-6559 + GAGGAGAGGCCCCUCCAGUG 20 6603

BCLllA-6560 + GGAGGAGAGGCCCCUCCAGUG 21 6604

BCLllA-6561 + GGGAGGAGAGGCCCCUCCAGUG 22 6605

BCLllA-6562 + GGGGAGGAGAGGCCCCUCCAGUG 23 6606

BCLllA-6563 + AGGGGAGGAGAGGCCCCUCCAGUG 24 6607

BCLllA-6564 + UGGCACUGCCCACAGGUG 18 6608

BCLllA-6565 + CUGGCACUGCCCACAGGUG 19 6609

BCLllA-5498 + UCUGGCACUGCCCACAGGUG 20 6610

BCLllA-6566 + AUCUGGCACUGCCCACAGGUG 21 6611

BCLllA-6567 + CAUCUGGCACUGCCCACAGGUG 22 6612

BCLllA-6568 + UCAUCUGGCACUGCCCACAGGUG 23 6613 BCLllA-6569 + U UCAUCUGGCACUGCCCACAGGUG 24 6614

BCLllA-6570 + U UUUCAUCUCGAUUGGUG 18 6615

BCLllA-6571 + U UUUUCAUCUCGAUUGGUG 19 6616

BCLllA-6572 + U UUUUUCAUCUCGAUUGGUG 20 6617

BCLllA-6573 + CUU UUUUCAUCUCGAUUGGUG 21 6618

BCLllA-6574 + GCUUUUUUCAUCUCGAUUGGUG 22 6619

BCLllA-6575 + UGCUUUUU UCAUCUCGAUUGGUG 23 6620

BCLllA-6576 + AUGCUUUUUUCAUCUCGAUUGGUG 24 6621

BCLllA-6577 + GGAUUAGAGCUCCAUGUG 18 6622

BCLllA-6578 + GGGAUUAGAGCUCCAUGUG 19 6623

BCLllA-6579 + GGGGAUUAGAGCUCCAUGUG 20 6624

BCLllA-6580 + UGGGGAUUAGAGCUCCAUGUG 21 6625

BCLllA-6581 + GUGGGGAUUAGAGCUCCAUGUG 22 6626

BCLllA-6582 + CGUGGGGAUUAGAGCUCCAUGUG 23 6627

BCLllA-6583 + GCGUGGGGAUUAGAGCUCCAUGUG 24 6628

BCLllA-6584 + CUUUUUUCAUCUCGAU UG 18 6629

BCLllA-6585 + GCUUUUUUCAUCUCGAUUG 19 6630

BCLllA-6586 + UGCUUUUU UCAUCUCGAUUG 20 6631

BCLllA-6587 + AUGCUUUUUUCAUCUCGAUUG 21 6632

BCLllA-6588 + GAUGCUUUUU UCAUCUCGAUUG 22 6633

BCLllA-6589 + GGAUGCUUUUU UCAUCUCGAUUG 23 6634

BCLllA-6590 + UGGAUGCUUUU UUCAUCUCGAUUG 24 6635

BCLllA-6591 + GAGGCUCGGCUGUGGUUG 18 6636

BCLllA-6592 + AGAGGCUCGGCUGUGGUUG 19 6637

BCLllA-6593 + AAGAGGCUCGGCUGUGGUUG 20 6638

BCLllA-6594 + CAAGAGGCUCGGCUGUGGUUG 21 6639

BCLllA-6595 + UCAAGAGGCUCGGCUGUGGUUG 22 6640

BCLllA-6596 + UUCAAGAGGCUCGGCUGUGGUUG 23 6641

BCLllA-6597 + CUUCAAGAGGCUCGGCUGUGGUUG 24 6642

BCLllA-6598 + AUAAGAAUGUCCCCCAAU 18 6643

BCLllA-6599 + AAUAAGAAUGUCCCCCAAU 19 6644

BCLllA-5502 + AAAUAAGAAUGUCCCCCAAU 20 6645

BCLllA-6600 + AAAAUAAGAAUGUCCCCCAAU 21 6646

BCLllA-6601 + AAAAAUAAGAAUGUCCCCCAAU 22 6647

BCLllA-6602 + UAAAAAUAAGAAUGUCCCCCAAU 23 6648

BCLllA-6603 + AUAAAAAUAAGAAUGUCCCCCAAU 24 6649

BCLllA-6604 + CAUCCCAGGCGUGGGGAU 18 6650

BCLllA-6605 + UCAUCCCAGGCGUGGGGAU 19 6651

BCLllA-6606 + CUCAUCCCAGGCGUGGGGAU 20 6652

BCLllA-6607 + ACUCAUCCCAGGCGUGGGGAU 21 6653

BCLllA-6608 + CACUCAUCCCAGGCGUGGGGAU 22 6654

BCLllA-6609 + GCACUCAUCCCAGGCGUGGGGAU 23 6655 BCLllA-6610 + UGCACUCAUCCCAGGCGUGGGGAU 24 6656

BCLllA-6611 + UCAACUUACAAAUACCCU 18 6657

BCLllA-6612 + CUCAACUUACAAAUACCCU 19 6658

BCLllA-6613 + G CU CAACU U ACAAAU ACCCU 20 6659

BCLllA-6614 + GGCUCAACUUACAAAUACCCU 21 6660

BCLllA-6615 + AGGCUCAACUUACAAAUACCCU 22 6661

BCLllA-6616 + AAGGCUCAACUUACAAAUACCCU 23 6662

BCLllA-6617 + UAAGGCUCAACUUACAAAUACCCU 24 6663

BCLllA-6618 + GGCGAGACAUGGUGGGCU 18 6664

BCLllA-6619 + CGGCGAGACAUGGUGGGCU 19 6665

BCLllA-6620 + GCGGCGAGACAUGGUGGGCU 20 6666

BCLllA-6621 + UGCGGCGAGACAUGGUGGGCU 21 6667

BCLllA-6622 + UUGCGGCGAGACAUGGUGGGCU 22 6668

BCLllA-6623 + CUUGCGGCGAGACAUGGUGGGCU 23 6669

BCLllA-6624 + GCUUGCGGCGAGACAUGGUGGGCU 24 6670

BCLllA-6625 + CAGUGCAGAAGUUUAUCU 18 6671

BCLllA-6626 + CCAGUGCAGAAGUUUAUCU 19 6672

BCLllA-6627 + UCCAGUGCAGAAGUUUAUCU 20 6673

BCLllA-6628 + CUCCAGUGCAGAAGUUUAUCU 21 6674

BCLllA-6629 + CCUCCAGUGCAGAAGUU UAUCU 22 6675

BCLllA-6630 + CCCUCCAGUGCAGAAGUUUAUCU 23 6676

BCLllA-6631 + CCCCUCCAGUGCAGAAGUUUAUCU 24 6677

BCLllA-6632 + CUGGCACUGCCCACAGGU 18 6678

BCLllA-6633 + UCUGGCACUGCCCACAGGU 19 6679

BCLllA-6634 + AUCUGGCACUGCCCACAGGU 20 6680

BCLllA-6635 + CAUCUGGCACUGCCCACAGGU 21 6681

BCLllA-6636 + UCAUCUGGCACUGCCCACAGGU 22 6682

BCLllA-6637 + U UCAUCUGGCACUGCCCACAGGU 23 6683

BCLllA-6638 + GUUCAUCUGGCACUGCCCACAGGU 24 6684

BCLllA-6639 + AAGAGGCUCGGCUGUGGU 18 6685

BCLllA-6640 + CAAGAGGCUCGGCUGUGGU 19 6686

BCLllA-5366 + UCAAGAGGCUCGGCUGUGGU 20 6687

BCLllA-6641 + U UCAAGAGGCUCGGCUGUGGU 21 6688

BCLllA-6642 + CUUCAAGAGGCUCGGCUGUGGU 22 6689

BCLllA-6643 + GCU UCAAGAGGCUCGGCUGUGGU 23 6690

BCLllA-6644 + GGCU UCAAGAGGCUCGGCUGUGGU 24 6691

BCLllA-6645 + CCUGCUAUGUGUUCCUGU 18 6692

BCLllA-6646 + ACCUGCUAUGUGUUCCUGU 19 6693

BCLllA-6647 + UACCUGCUAUGUGUUCCUGU 20 6694

BCLllA-6648 + UUACCUGCUAUGUGUUCCUGU 21 6695

BCLllA-6649 + UUUACCUGCUAUGUGUUCCUGU 22 6696

BCLllA-6650 + AUUUACCUGCUAUGUGUUCCUGU 23 6697 BCLllA-6651 + CAUUUACCUGCUAUGUGUUCCUGU 24 6698

BCLllA-6652 + GGAGGUCAUGAUCCCCUU 18 6699

BCLllA-6653 + AGGAGGUCAUGAUCCCCUU 19 6700

BCLllA-6654 + GAGGAGGUCAUGAUCCCCUU 20 6701

BCLllA-6655 + UGAGGAGGUCAUGAUCCCCUU 21 6702

BCLllA-6656 + GUGAGGAGGUCAUGAUCCCCU U 22 6703

BCLllA-6657 + GGUGAGGAGGUCAUGAUCCCCUU 23 6704

BCLllA-6658 + AGGUGAGGAGGUCAUGAUCCCCUU 24 6705

BCLllA-6659 + CUGCUAUGUGUUCCUGUU 18 6706

BCLllA-6660 + CCUGCUAUGUGUUCCUGUU 19 6707

BCLllA-5513 + ACCUGCUAUGUGUUCCUGUU 20 6708

BCLllA-6661 + UACCUGCUAUGUGUUCCUGUU 21 6709

BCLllA-6662 + UUACCUGCUAUGUGUUCCUGUU 22 6710

BCLllA-6663 + UUUACCUGCUAUGUGUUCCUGUU 23 6711

BCLllA-6664 + AUUUACCUGCUAUGUGUUCCUGUU 24 6712

BCLllA-6665 - AUUUUUAUCGAGCACAAA 18 6713

BCLllA-6666 - UAUUUUUAUCGAGCACAAA 19 6714

BCLllA-5342 - U UAUUUUUAUCGAGCACAAA 20 6715

BCLllA-6667 - CUUAUUUUUAUCGAGCACAAA 21 6716

BCLllA-6668 - UCUUAUUUU UAUCGAGCACAAA 22 6717

BCLllA-6669 - U UCUUAUUU UUAUCGAGCACAAA 23 6718

BCLllA-6670 - AUUCUUAUUUUUAUCGAGCACAAA 24 6719

BCLllA-6671 - AGAGGAAUUUGCCCCAAA 18 6720

BCLllA-6672 - UAGAGGAAUUUGCCCCAAA 19 6721

BCLllA-6673 - CUAGAGGAAUUUGCCCCAAA 20 6722

BCLllA-6674 - UCUAGAGGAAUUUGCCCCAAA 21 6723

BCLllA-6675 - AUCUAGAGGAAUUUGCCCCAAA 22 6724

BCLllA-6676 - CAUCUAGAGGAAUUUGCCCCAAA 23 6725

BCLllA-6677 - UCAUCUAGAGGAAUUUGCCCCAAA 24 6726

BCLllA-6678 - CCCCAGCACUUAAGCAAA 18 6727

BCLllA-6679 - ACCCCAGCACUUAAGCAAA 19 6728

BCLllA-5443 - AACCCCAGCACU UAAGCAAA 20 6729

BCLllA-6680 - AAACCCCAGCACUUAAGCAAA 21 6730

BCLllA-6681 - CAAACCCCAGCACU UAAGCAAA 22 6731

BCLllA-6682 - GCAAACCCCAGCACUUAAGCAAA 23 6732

BCLllA-6683 - G G C A A AC CC C AG C A C U U A AG C A A A 24 6733

BCLllA-6684 - UAUUUUUAUCGAGCACAA 18 6734

BCLllA-6685 - UUAUUUUUAUCGAGCACAA 19 6735

BCLllA-6686 - CUUAUUUUUAUCGAGCACAA 20 6736

BCLllA-6687 - UCU UAUUUUUAUCGAGCACAA 21 6737

BCLllA-6688 - UUCUUAUUUUUAUCGAGCACAA 22 6738

BCLllA-6689 - AUUCUUAUUUU UAUCGAGCACAA 23 6739 BCLllA-6690 - CAUUCUUAUUUUUAUCGAGCACAA 24 6740

BCLllA-6691 - CACCUUCCCCUUCACCAA 18 6741

BCLllA-6692 - CCACCUUCCCCUUCACCAA 19 6742

BCLllA-6693 - GCCACCUUCCCCUUCACCAA 20 6743

BCLllA-6694 - AG CCACCU U CCCCU U CACCAA 21 6744

BCLllA-6695 - AAGCCACCUUCCCCUUCACCAA 22 6745

BCLllA-6696 - U AAGCCACCU U CCCCU U CACCAA 23 6746

BCLllA-6697 - AUAAGCCACCUUCCCCUUCACCAA 24 6747

BCLllA-6698 - ACCCCAGCACUUAAGCAA 18 6748

BCLllA-6699 - AACCCCAGCACUUAAGCAA 19 6749

BCLllA-6700 - AAACCCCAGCACUUAAGCAA 20 6750

BCLllA-6701 - CAAACCCCAGCACUUAAGCAA 21 6751

BCLllA-6702 - GCAAACCCCAGCACUUAAGCAA 22 6752

BCLllA-6703 - GGCAAACCCCAGCACUUAAGCAA 23 6753

BCLllA-6704 - AGGCAAACCCCAGCACUUAAGCAA 24 6754

BCLllA-6705 - GGAACACAUAGCAGGUAA 18 6755

BCLllA-6706 - AGGAACACAUAGCAGGUAA 19 6756

BCLllA-6707 - CAGGAACACAUAGCAGGUAA 20 6757

BCLllA-6708 - ACAGGAACACAUAGCAGGUAA 21 6758

BCLllA-6709 - AACAGGAACACAUAGCAGGUAA 22 6759

BCLllA-6710 - AAACAGGAACACAUAGCAGGUAA 23 6760

BCLllA-6711 - CAAACAGGAACACAUAGCAGGUAA 24 6761

BCLllA-6712 - CUCCCCUCGUUCUGCACA 18 6762

BCLllA-6713 - CCUCCCCUCGUUCUGCACA 19 6763

BCLllA-5448 - UCCUCCCCUCGUUCUGCACA 20 6764

BCLllA-6714 - CUCCUCCCCUCGUUCUGCACA 21 6765

BCLllA-6715 - UCUCCUCCCCUCGUUCUGCACA 22 6766

BCLllA-6716 - CUCUCCUCCCCUCGUUCUGCACA 23 6767

BCLllA-6717 - CCUCUCCUCCCCUCGUUCUGCACA 24 6768

BCLllA-6718 - UGCCAGAUGAACUUCCCA 18 6769

BCLllA-6719 - GUGCCAGAUGAACUUCCCA 19 6770

BCLllA-6720 - AGUGCCAGAUGAACUUCCCA 20 6771

BCLllA-6721 - CAGUGCCAGAUGAACUUCCCA 21 6772

BCLllA-6722 - GCAGUGCCAGAUGAACUUCCCA 22 6773

BCLllA-6723 - GGCAGUGCCAGAUGAACUUCCCA 23 6774

BCLllA-6724 - GGGCAGUGCCAGAUGAACUUCCCA 24 6775

BCLllA-6725 - G C AG G U AAA UGAGAAGCA 18 6776

BCLllA-6726 - AGCAGGUAAAUGAGAAGCA 19 6777

BCLllA-5451 - UAGCAGGUAAAUGAGAAGCA 20 6778

BCLllA-6727 - AUAGCAGGU AAA U G AG A AG C A 21 6779

BCLllA-6728 - CAUAGCAGGUAAAUGAGAAGCA 22 6780

BCLllA-6729 - ACAU AGCAGGUAAAUGAGAAGCA 23 6781 BCLllA-6730 - CACAUAGCAGGUAAAUGAGAAGCA 24 6782

BCLllA-6731 - CACAGAUAAACUUCUGCA 18 6783

BCLllA-6732 - UCACAGAUAAACUUCUGCA 19 6784

BCLllA-6733 - UUCACAGAUAAACUUCUGCA 20 6785

BCLllA-6734 - UUUCACAGAUAAACUUCUGCA 21 6786

BCLllA-6735 - CUUUCACAGAUAAACUUCUGCA 22 6787

BCLllA-6736 - UCUUUCACAGAUAAACUUCUGCA 23 6788

BCLllA-6737 - UUCUUUCACAGAUAAACUUCUGCA 24 6789

BCLllA-6738 - CCCGUUGGGAGCUCCAGA 18 6790

BCLllA-6739 - GCCCGUUGGGAGCUCCAGA 19 6791

BCLllA-5453 - GGCCCGUUGGGAGCUCCAGA 20 6792

BCLllA-6740 - CGGCCCGUUGGGAGCUCCAGA 21 6793

BCLllA-6741 - ACGGCCCGUUGGGAGCUCCAGA 22 6794

BCLllA-6742 - CACGGCCCGUUGGGAGCUCCAGA 23 6795

BCLllA-6743 - CCACGGCCCGUUGGGAGCUCCAGA 24 6796

BCLllA-6744 - GUUUAUCAACGUCAUCUA 18 6797

BCLllA-6745 - UGUUUAUCAACGUCAUCUA 19 6798

BCLllA-6746 - UUGUUUAUCAACGUCAUCUA 20 6799

BCLllA-6747 - AUUGUUUAUCAACGUCAUCUA 21 6800

BCLllA-6748 - GAUUGUUUAUCAACGUCAUCUA 22 6801

BCLllA-6749 - CGAUUGUUUAUCAACGUCAUCUA 23 6802

BCLllA-6750 - ACGAUUGUUUAUCAACGUCAUCUA 24 6803

BCLllA-6751 - GGGACAUUCUUAUUUUUA 18 6804

BCLllA-6752 - GGGGACAUUCUUAUUUUUA 19 6805

BCLllA-6753 - GGGGGACAUUCUUAUUUUUA 20 6806

BCLllA-6754 - UGGGGGACAUUCUUAUUUUUA 21 6807

BCLllA-6755 - UUGGGGGACAUUCUUAUUUUUA 22 6808

BCLllA-6756 - AUUGGGGGACAUUCUUAUUUUUA 23 6809

BCLllA-6757 - CAUUGGGGGACAUUCUUAUUUUUA 24 6810

BCLllA-6758 - GAGGAAUUUGCCCCAAAC 18 6811

BCLllA-6759 - AGAGGAAUUUGCCCCAAAC 19 6812

BCLllA-5457 - UAGAGGAAUUUGCCCCAAAC 20 6813

BCLllA-6760 - CUAGAGGAAUUUGCCCCAAAC 21 6814

BCLllA-6761 - UCUAGAGGAAUUUGCCCCAAAC 22 6815

BCLllA-6762 - AUCUAGAGGAAUUUGCCCCAAAC 23 6816

BCLllA-6763 - CAUCUAGAGGAAUUUGCCCCAAAC 24 6817

BCLllA-6764 - ACAGAUAAACUUCUGCAC 18 6818

BCLllA-6765 - CACAGAUAAACUUCUGCAC 19 6819

BCLllA-5348 - UCACAGAUAAACUUCUGCAC 20 6820

BCLllA-6766 - UUCACAGAUAAACUUCUGCAC 21 6821

BCLllA-6767 - UUUCACAGAUAAACUUCUGCAC 22 6822

BCLllA-6768 - CUUUCACAGAUAAACUUCUGCAC 23 6823 BCLllA-6769 - UCUUUCACAGAUAAACUUCUGCAC 24 6824

BCLllA-6770 - CCUCCCCUCGUUCUGCAC 18 6825

BCLllA-6771 - UCCUCCCCUCGUUCUGCAC 19 6826

BCLllA-6772 - CUCCUCCCCUCGUUCUGCAC 20 6827

BCLllA-6773 - UCUCCUCCCCUCGUUCUGCAC 21 6828

BCLllA-6774 - CUCUCCUCCCCUCGUUCUGCAC 22 6829

BCLllA-6775 - CCUCUCCUCCCCUCGUUCUGCAC 23 6830

BCLllA-6776 - GCCUCUCCUCCCCUCGUUCUGCAC 24 6831

BCLllA-6777 - A A A A A AG C A U C C A A U C C C 18 6832

BCLllA-6778 - GAAAAAAGCAUCCAAUCCC 19 6833

BCLllA-6779 - UGAAAAAAGCAUCCAAUCCC 20 6834

BCLllA-6780 - AUGAAAAAAGCAUCCAAUCCC 21 6835

BCLllA-6781 - GAUGAAAAAAGCAUCCAAUCCC 22 6836

BCLllA-6782 - AGAUGAAAAAAGCAUCCAAUCCC 23 6837

BCLllA-6783 - GAGAUGAAAAAAGCAUCCAAUCCC 24 6838

BCLllA-6784 - AG C AG G U AAA U G AG A AG C 18 6839

BCLllA-6785 - U AG C AG G U AAA U G AG A AG C 19 6840

BCLllA-6786 - AUAGCAGGUAAAUGAGAAGC 20 6841

BCLllA-6787 - CAUAGCAGGUAAAUGAGAAGC 21 6842

BCLllA-6788 - ACAUAGCAGGU AAA U G AG A AG C 22 6843

BCLllA-6789 - CACAUAGCAGGU AAA U G AG A AG C 23 6844

BCLllA-6790 - ACACAUAGCAGGUAAAUGAGAAGC 24 6845

BCLllA-6791 - GAGCUCUAAUCCCCACGC 18 6846

BCLllA-6792 - GGAGCUCUAAUCCCCACGC 19 6847

BCLllA-6793 - UGGAGCUCUAAUCCCCACGC 20 6848

BCLllA-6794 - AUGGAGCUCUAAUCCCCACGC 21 6849

BCLllA-6795 - CAUGGAGCUCUAAUCCCCACGC 22 6850

BCLllA-6796 - ACAUGGAGCUCUAAUCCCCACGC 23 6851

BCLllA-6797 - CACAUGGAGCUCUAAUCCCCACGC 24 6852

BCLllA-6798 - UUGGCAUCCAGGUCACGC 18 6853

BCLllA-6799 - GUUGGCAUCCAGGUCACGC 19 6854

BCLllA-6800 - GGUUGGCAUCCAGGUCACGC 20 6855

BCLllA-6801 - AGGUUGGCAUCCAGGUCACGC 21 6856

BCLllA-6802 - GAGGUUGGCAUCCAGGUCACGC 22 6857

BCLllA-6803 - GGAGGUUGGCAUCCAGGUCACGC 23 6858

BCLllA-6804 - UGGAGGUUGGCAUCCAGGUCACGC 24 6859

BCLllA-6805 - UUGUUUAUCAACGUCAUC 18 6860

BCLllA-6806 - AUUGUUUAUCAACGUCAUC 19 6861

BCLllA-6807 - GAUUGUUUAUCAACGUCAUC 20 6862

BCLllA-6808 - CGAUUGUUUAUCAACGUCAUC 21 6863

BCLllA-6809 - ACGAUUGUUUAUCAACGUCAUC 22 6864

BCLllA-6810 - GACGAUUGUUUAUCAACGUCAUC 23 6865 BCLllA-6811 - UGACGAUUGUUUAUCAACGUCAUC 24 6866

BCLllA-6812 - CAACCACAGCCGAGCCUC 18 6867

BCLllA-6813 - CCAACCACAG CCG AG CCU C 19 6868

BCLllA-6814 - UCCAACCACAGCCGAGCCUC 20 6869

BCLllA-6815 - CUCCAACCACAGCCGAGCCUC 21 6870

BCLllA-6816 - UCUCCAACCACAGCCGAGCCUC 22 6871

BCLllA-6817 - UUCUCCAACCACAGCCGAGCCUC 23 6872

BCLllA-6818 - UUUCUCCAACCACAGCCGAGCCUC 24 6873

BCLllA-6819 - ACGGCCCGUUGGGAGCUC 18 6874

BCLllA-6820 - CACGGCCCGUUGGGAGCUC 19 6875

BCLllA-6821 - CCACGGCCCGUUGGGAGCUC 20 6876

BCLllA-6822 - ACCACGGCCCGUUGGGAGCUC 21 6877

BCLllA-6823 - GACCACGGCCCGUUGGGAGCUC 22 6878

BCLllA-6824 - AGACCACGGCCCGUUGGGAGCUC 23 6879

BCLllA-6825 - CAGACCACGGCCCGUUGGGAGCUC 24 6880

BCLllA-6826 - AUUAUUUUGCAGGUAAAG 18 6881

BCLllA-6827 - UAUUAUUUUGCAGGUAAAG 19 6882

BCLllA-6828 - GUAUUAUUUUGCAGGUAAAG 20 6883

BCLllA-6829 - UGUAUUAUUUUGCAGGUAAAG 21 6884

BCLllA-6830 - UUGUAUUAUUUUGCAGGUAAAG 22 6885

BCLllA-6831 - GUUGUAUUAUUUUGCAGGUAAAG 23 6886

BCLllA-6832 - UGUUGUAUUAUUUUGCAGGUAAAG 24 6887

BCLllA-6833 - AGGUAAAUGAGAAGCAAG 18 6888

BCLllA-6834 - C AG G U AAA U G AG A AG C A AG 19 6889

BCLllA-6835 - G C AG G U AAA UGAGAAGCAAG 20 6890

BCLllA-6836 - AG C AG G U AAA U G AG A AG C A AG 21 6891

BCLllA-6837 - U AG C AG G U AAA U G AG A AG C A AG 22 6892

BCLllA-6838 - AUAGCAGGUAAAUGAGAAGCAAG 23 6893

BCLllA-6839 - CAUAGCAGGUAAAUGAGAAGCAAG 24 6894

BCLllA-6840 - CCGCAGGGUAUUUGUAAG 18 6895

BCLllA-6841 - CCCGCAGGGUAUUUGUAAG 19 6896

BCLllA-6842 - CCCCGCAGGGUAUUUGUAAG 20 6897

BCLllA-6843 - GCCCCGCAGGGUAUUUGUAAG 21 6898

BCLllA-6844 - UGCCCCGCAGGGUAUUUGUAAG 22 6899

BCLllA-6845 - AUGCCCCGCAGGGUAUUUGUAAG 23 6900

BCLllA-6846 - UAUGCCCCGCAGGGUAUUUGUAAG 24 6901

BCLllA-6847 - UUGUUUCUCCAACCACAG 18 6902

BCLllA-6848 - UUUGUUUCUCCAACCACAG 19 6903

BCLllA-6849 - UUUUGUUUCUCCAACCACAG 20 6904

BCLllA-6850 - CUUUUGUUUCUCCAACCACAG 21 6905

BCLllA-6851 - GCUUUUGUUUCUCCAACCACAG 22 6906

BCLllA-6852 - UGCUUUUGUUUCUCCAACCACAG 23 6907 BCLllA-6853 - GUGCUUUUGUUUCUCCAACCACAG 24 6908

BCLllA-6854 - ACCUGUGGGCAGUGCCAG 18 6909

BCLllA-6855 - CACCUGUGGGCAGUGCCAG 19 6910

BCLllA-6856 - UCACCUGUGGGCAGUGCCAG 20 6911

BCLllA-6857 - CUCACCUGUGGGCAGUGCCAG 21 6912

BCLllA-6858 - CCUCACCUGUGGGCAGUGCCAG 22 6913

BCLllA-6859 - UCCUCACCUGUGGGCAGUGCCAG 23 6914

BCLllA-6860 - CUCCUCACCUGUGGGCAGUGCCAG 24 6915

BCLllA-6861 - GCCCGUUGGGAGCUCCAG 18 6916

BCLllA-6862 - GGCCCGUUGGGAGCUCCAG 19 6917

BCLllA-6863 - CGGCCCGUUGGGAGCUCCAG 20 6918

BCLllA-6864 - ACGGCCCGUUGGGAGCUCCAG 21 6919

BCLllA-6865 - CACGGCCCGUUGGGAGCUCCAG 22 6920

BCLllA-6866 - CCACGGCCCGUUGGGAGCUCCAG 23 6921

BCLllA-6867 - ACCACGGCCCGUUGGGAGCUCCAG 24 6922

BCLllA-6868 - UCCCCUUCACCAAUCGAG 18 6923

BCLllA-6869 - UUCCCCUUCACCAAUCGAG 19 6924

BCLllA-6870 - CUUCCCCUUCACCAAUCGAG 20 6925

BCLllA-6871 - CCUUCCCCUUCACCAAUCGAG 21 6926

BCLllA-6872 - ACCUUCCCCUUCACCAAUCGAG 22 6927

BCLllA-6873 - CACCU U CCCCU U CACCAAU CG AG 23 6928

BCLllA-6874 - CCACCUUCCCCUUCACCAAUCGAG 24 6929

BCLllA-6875 - GAACCAGACCACGGCCCG 18 6930

BCLllA-6876 - UGAACCAGACCACGGCCCG 19 6931

BCLllA-6877 - AUGAACCAGACCACGGCCCG 20 6932

BCLllA-6878 - GAUGAACCAGACCACGGCCCG 21 6933

BCLllA-6879 - UGAUGAACCAGACCACGGCCCG 22 6934

BCLllA-6880 - AUGAUGAACCAGACCACGGCCCG 23 6935

BCLllA-6881 - GAUGAUGAACCAGACCACGGCCCG 24 6936

BCLllA-6882 - AAAAAGCAUCCAAUCCCG 18 6937

BCLllA-6883 - A A A A A AG C A U C C A A U C C CG 19 6938

BCLllA-5358 - GAAAAAAGCAUCCAAUCCCG 20 6939

BCLllA-6884 - UGAAAAAAGCAUCCAAUCCCG 21 6940

BCLllA-6885 - AUG A A A A A AG CAUCCAAUCCCG 22 6941

BCLllA-6886 - GAUGAAAAAAGCAUCCAAUCCCG 23 6942

BCLllA-6887 - AGAUGAAAAAAGCAUCCAAUCCCG 24 6943

BCLllA-6888 - GAUAAACUUCUGCACUGG 18 6944

BCLllA-6889 - AGAUAAACUUCUGCACUGG 19 6945

BCLllA-5360 - CAGAUAAACUUCUGCACUGG 20 6946

BCLllA-6890 - ACAGAUAAACUUCUGCACUGG 21 6947

BCLllA-6891 - CACAGAUAAACUUCUGCACUGG 22 6948

BCLllA-6892 - UCA CAGAUAAACUUCUGCACUGG 23 6949 BCLllA-6893 - UUCACAGAUAAACUUCUGCACUGG 24 6950

BCLllA-6894 - AAGCCAUUCUUACAGAUG 18 6951

BCLllA-6895 - GAAGCCAUUCUUACAGAUG 19 6952

BCLllA-6896 - UGAAGCCAUUCUUACAGAUG 20 6953

BCLllA-6897 - UUGAAGCCAUUCUUACAGAUG 21 6954

BCLllA-6898 - CUUGAAGCCAUUCUUACAGAUG 22 6955

BCLllA-6899 - UCUUGAAGCCAUUCUUACAGAUG 23 6956

BCLllA-6900 - CUCUUGAAGCCAUUCUUACAGAUG 24 6957

BCLllA-6901 - AGAUAAACUUCUGCACUG 18 6958

BCLllA-6902 - CAGAUAAACUUCUGCACUG 19 6959

BCLllA-6903 - ACAGAUAAACUUCUGCACUG 20 6960

BCLllA-6904 - CACAGAUAAACUUCUGCACUG 21 6961

BCLllA-6905 - UCA CAGAUAAACUUCUGCACUG 22 6962

BCLllA-6906 - UUCACAGAUAAACUUCUGCACUG 23 6963

BCLllA-6907 - UUUCACAGAUAAACUUCUGCACUG 24 6964

BCLllA-6908 - CAGAUGAACUUCCCAUUG 18 6965

BCLllA-6909 - CCAGAUGAACUUCCCAUUG 19 6966

BCLllA-5499 - GCCAGAUGAACUUCCCAUUG 20 6967

BCLllA-6910 - UGCCAGAUGAACUUCCCAUUG 21 6968

BCLllA-6911 - GUGCCAGAUGAACUUCCCAUUG 22 6969

BCLllA-6912 - AGUGCCAGAUGAACUUCCCAUUG 23 6970

BCLllA-6913 - CAGUGCCAGAUGAACUUCCCAUUG 24 6971

BCLllA-6914 - AACACAUAGCAGGUAAAU 18 6972

BCLllA-6915 - GAACACAUAGCAGGUAAAU 19 6973

BCLllA-6916 - GGAACACAUAGCAGGUAAAU 20 6974

BCLllA-6917 - AGGAACACAUAGCAGGUAAAU 21 6975

BCLllA-6918 - CAGGAACACAUAGCAGGUAAAU 22 6976

BCLllA-6919 - ACAGGAACACAUAGCAGGUAAAU 23 6977

BCLllA-6920 - AACAGGAACACAUAGCAGGUAAAU 24 6978

BCLllA-6921 - GCCAGAUGAACUUCCCAU 18 6979

BCLllA-6922 - UGCCAGAUGAACUUCCCAU 19 6980

BCLllA-5503 - GUGCCAGAUGAACUUCCCAU 20 6981

BCLllA-6923 - AGUGCCAGAUGAACUUCCCAU 21 6982

BCLllA-6924 - CAGUGCCAGAUGAACUUCCCAU 22 6983

BCLllA-6925 - GCAGUGCCAGAUGAACUUCCCAU 23 6984

BCLllA-6926 - GGCAGUGCCAGAUGAACUUCCCAU 24 6985

BCLllA-6927 - AUCAUGACCUCCUCACCU 18 6986

BCLllA-6928 - GAUCAUGACCUCCUCACCU 19 6987

BCLllA-6929 - GGAUCAUGACCUCCUCACCU 20 6988

BCLllA-6930 - GGGAUCAUGACCUCCUCACCU 21 6989

BCLllA-6931 - GGGGAUCAUGACCUCCUCACCU 22 6990

BCLllA-6932 - AGGGGAUCAUGACCUCCUCACCU 23 6991 BCLllA-6933 - AAGGGGAUCAUGACCUCCUCACCU 24 6992

BCLllA-6934 - GCAAUGGCAGCCUCUGCU 18 6993

BCLllA-6935 - UGCAAUGGCAGCCUCUGCU 19 6994

BCLllA-6936 - AUGCAAUGGCAGCCUCUGCU 20 6995

BCLllA-6937 - AAUGCAAUGGCAGCCUCUGCU 21 6996

BCLllA-6938 - CAAUGCAAUGGCAGCCUCUGCU 22 6997

BCLllA-6939 - ACAAUGCAAUGGCAGCCUCUGCU 23 6998

BCLllA-6940 - AACAAUGCAAUGGCAGCCUCUGCU 24 6999

BCLllA-6941 - AACCAGACCACGGCCCGU 18 7000

BCLllA-6942 - GAACCAGACCACGGCCCGU 19 7001

BCLllA-5363 - UGAACCAGACCACGGCCCGU 20 7002

BCLllA-6943 - AUGAACCAGACCACGGCCCGU 21 7003

BCLllA-6944 - GAUGAACCAGACCACGGCCCGU 22 7004

BCLllA-6945 - UGAUGAACCAGACCACGGCCCGU 23 7005

BCLllA-6946 - AUGAUGAACCAGACCACGGCCCGU 24 7006

BCLllA-6947 - CCAGAUGAACUUCCCAUU 18 7007

BCLllA-6948 - GCCAGAUGAACUUCCCAUU 19 7008

BCLllA-5511 - UGCCAGAUGAACUUCCCAUU 20 7009

BCLllA-6949 - GUGCCAGAUGAACUUCCCAUU 21 7010

BCLllA-6950 - AGUGCCAGAUGAACUUCCCAUU 22 7011

BCLllA-6951 - CAGUGCCAGAUGAACUUCCCAUU 23 7012

BCLllA-6952 - GCAGUGCCAGAUGAACUUCCCAUU 24 7013

BCLllA-6953 - ACCAG ACCACGG CCCG U U 18 7014

BCLllA-6954 - AACCAG ACCACGG CCCG U U 19 7015

BCLllA-5512 - GAACCAG ACCACGG CCCG U U 20 7016

BCLllA-6955 - UG AACCAG ACCACGG CCCG U U 21 7017

BCLllA-6956 - AUGAACCAGACCACGGCCCGUU 22 7018

BCLllA-6957 - GAUGAACCAGACCACGGCCCGUU 23 7019

BCLllA-6958 - UGAUGAACCAGACCACGGCCCGUU 24 7020

Table 13D provides exemplary targeting domains for knocking out the BCL11A gene selected according to the fourth 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 the 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 13D 4th Tier

DNA Target Site SEQ ID gRNA Name Targeting Domain

Strand Length NO

BCLllA-6959 + GUAUUCUUAGCAGGUUAA 18 7021

BCLllA-6960 + GGUAUUCUUAGCAGGUUAA 19 7022

BCLllA-5890 + UGGUAUUCUUAGCAGGUUAA 20 7023

BCLllA-6961 + CUGGUAUUCUUAGCAGGUUAA 21 7024

BCLllA-6962 + CCUGGUAUUCUUAGCAGGUUAA 22 7025

BCLllA-6963 + UCCUGGUAU UCUUAGCAGGUUAA 23 7026

BCLllA-6964 + AUCCUGGUAUUCUUAGCAGGUUAA 24 7027

BCLllA-6965 + CGGGAGGCUCCAUAGCCA 18 7028

BCLllA-6966 + GCGGGAGGCUCCAUAGCCA 19 7029

BCLllA-6967 + GGCGGGAGGCUCCAUAGCCA 20 7030

BCLllA-6968 + UGGCGGGAGGCUCCAUAGCCA 21 7031

BCLllA-6969 + AUGGCGGGAGGCUCCAUAGCCA 22 7032

BCLllA-6970 + CAUGGCGGGAGGCUCCAUAGCCA 23 7033

BCLllA-6971 + CCAUGGCGGGAGGCUCCAUAGCCA 24 7034

BCLllA-6972 + GGUCCGACUCGCCGGCCA 18 7035

BCLllA-6973 + CGGUCCGACUCGCCGGCCA 19 7036

BCLllA-6974 + GCGGUCCGACUCGCCGGCCA 20 7037

BCLllA-6975 + UGCGGUCCGACUCGCCGGCCA 21 7038

BCLllA-6976 + AUGCGGUCCGACUCGCCGGCCA 22 7039

BCLllA-6977 + UAUGCGGUCCGACUCGCCGGCCA 23 7040

BCLllA-6978 + CUAUGCGGUCCGACUCGCCGGCCA 24 7041

BCLllA-6979 + AGUCUCCGAAGCUAAGGA 18 7042

BCLllA-6980 + GAGUCUCCGAAGCUAAGGA 19 7043

BCLllA-5923 + GGAGUCUCCGAAGCUAAGGA 20 7044

BCLllA-6981 + UGGAGUCUCCGAAGCUAAGGA 21 7045

BCLllA-6982 + CUGGAGUCUCCGAAGCUAAGGA 22 7046

BCLllA-6983 + UCUGGAGUCUCCGAAGCUAAGGA 23 7047

BCLllA-6984 + GUCUGGAGUCUCCGAAGCUAAGGA 24 7048

BCLllA-6985 + GGACUAAACAGGGGGGGA 18 7049

BCLllA-6986 + UGGACUAAACAGGGGGGGA 19 7050

BCLllA-6987 + GUGGACUAAACAGGGGGGGA 20 7051

BCLllA-6988 + GGUGGACUAAACAGGGGGGGA 21 7052

BCLllA-6989 + UGGUGGACUAAACAGGGGGGGA 22 7053

BCLllA-6990 + GUGGUGGACUAAACAGGGGGGGA 23 7054

BCLllA-6991 + GGUGGUGGACUAAACAGGGGGGGA 24 7055

BCLllA-6992 + U UCUGCACCUAGUCCUGA 18 7056

BCLllA-6993 + AUUCUGCACCUAGUCCUGA 19 7057

BCLllA-5937 + CAU UCUGCACCUAGUCCUGA 20 7058

BCLllA-6994 + ACAUUCUGCACCUAGUCCUGA 21 7059 BCLllA-6995 + GACAUUCUGCACCUAGUCCUGA 22 7060

BCLllA-6996 + GGACAUUCUGCACCUAGUCCUGA 23 7061

BCLllA-6997 + AGGACAUUCUGCACCUAGUCCUGA 24 7062

BCLllA-6998 + GCACCCUGUCAAAGGCAC 18 7063

BCLllA-6999 + AGCACCCUGUCAAAGGCAC 19 7064

BCLllA-7000 + CAGCACCCUGUCAAAGGCAC 20 7065

BCLllA-7001 + G C AG CACCCUGU CAAAG G CAC 21 7066

BCLllA-7002 + CGCAGCACCCUGUCAAAGGCAC 22 7067

BCLllA-7003 + CCGCAGCACCCUGUCAAAGGCAC 23 7068

BCLllA-7004 + ACCGCAGCACCCUGUCAAAGGCAC 24 7069

BCLllA-7005 + UAAGUAGAUUCUUAAUCC 18 7070

BCLllA-7006 + CUAAGUAGAUUCUUAAUCC 19 7071

BCLllA-7007 + UCUAAGUAGAUUCUUAAUCC 20 7072

BCLllA-7008 + U UCUAAGUAGAUUCUUAAUCC 21 7073

BCLllA-7009 + U UUCUAAGUAGAUUCU UAAUCC 22 7074

BCLllA-7010 + CUU UCUAAGUAGAUUCUUAAUCC 23 7075

BCLllA-7011 + GCU UUCUAAGUAGAU UCUUAAUCC 24 7076

BCLllA-7012 + GGCGGCU UGCUACCUGGC 18 7077

BCLllA-7013 + GGGCGGCU UGCUACCUGGC 19 7078

BCLllA-6036 + AGGGCGGCUUGCUACCUGGC 20 7079

BCLllA-7014 + AAGGGCGGCUUGCUACCUGGC 21 7080

BCLllA-7015 + GAAGGGCGGCUUGCUACCUGGC 22 7081

BCLllA-7016 + GGAAGGGCGGCUUGCUACCUGGC 23 7082

BCLllA-7017 + AGGAAGGGCGGCUUGCUACCUGGC 24 7083

BCLllA-7018 + GCGCUUCAGCUUGCUGGC 18 7084

BCLllA-7019 + GGCGCUUCAGCUUGCUGGC 19 7085

BCLllA-7020 + UGGCGCUUCAGCUUGCUGGC 20 7086

BCLllA-7021 + GUGGCGCUUCAGCUUGCUGGC 21 7087

BCLllA-7022 + UGUGGCGCUUCAGCUUGCUGGC 22 7088

BCLllA-7023 + AUGUGGCGCUUCAGCUUGCUGGC 23 7089

BCLllA-7024 + CAUGUGGCGCUUCAGCU UGCUGGC 24 7090

BCLllA-7025 + CUCCUCGUCCCCGU UCUC 18 7091

BCLllA-7026 + CCUCCUCGUCCCCGUUCUC 19 7092

BCLllA-6050 + UCCUCCUCGUCCCCGUUCUC 20 7093

BCLllA-7027 + UUCCUCCUCGUCCCCGUUCUC 21 7094

BCLllA-7028 + CUUCCUCCUCGUCCCCGUUCUC 22 7095

BCLllA-7029 + UCU UCCUCCUCGUCCCCGUUCUC 23 7096

BCLllA-7030 + CUCU UCCUCCUCGUCCCCGUUCUC 24 7097

BCLllA-7031 + AGGCAAAAGGCGAUUGUC 18 7098

BCLllA-7032 + GAGGCAAAAGGCGAUUGUC 19 7099

BCLllA-6054 + GGAGGCAAAAGGCGAU UGUC 20 7100

BCLllA-7033 + AGGAGGCAAAAGGCGAUUGUC 21 7101 BCLllA-7034 + GAGGAGGCAAAAGGCGAUUGUC 22 7102

BCLllA-7035 + CGAGGAGGCAAAAGGCGAUUGUC 23 7103

BCLllA-7036 + ACGAGGAGGCAAAAGGCGAUUGUC 24 7104

BCLllA-7037 + AGCUCUCUGGGUACUACG 18 7105

BCLllA-7038 + GAGCUCUCUGGGUACUACG 19 7106

BCLllA-7039 + UGAGCUCUCUGGGUACUACG 20 7107

BCLllA-7040 + U UGAGCUCUCUGGGUACUACG 21 7108

BCLllA-7041 + CUUGAGCUCUCUGGGUACUACG 22 7109

BCLllA-7042 + UCU UGAGCUCUCUGGGUACUACG 23 7110

BCLllA-7043 + AUCUUGAGCUCUCUGGGUACUACG 24 7111

BCLllA-7044 + UGAAGGGAUACCAACCCG 18 7112

BCLllA-7045 + CUGAAGGGAUACCAACCCG 19 7113

BCLllA-6084 + CCUGAAGGGAUACCAACCCG 20 7114

BCLllA-7046 + UCCUGAAGGGAUACCAACCCG 21 7115

BCLllA-7047 + GUCCUGAAGGGAUACCAACCCG 22 7116

BCLllA-7048 + AGUCCUGAAGGGAUACCAACCCG 23 7117

BCLllA-7049 + UAGUCCUGAAGGGAUACCAACCCG 24 7118

BCLllA-7050 + GCAAACUCCCGUUCUCCG 18 7119

BCLllA-7051 + CGCAAACUCCCGUUCUCCG 19 7120

BCLllA-6094 + GCGCAAACUCCCGUUCUCCG 20 7121

BCLllA-7052 + AGCGCAAACUCCCGUUCUCCG 21 7122

BCLllA-7053 + AAGCGCAAACUCCCGUUCUCCG 22 7123

BCLllA-7054 + GAAGCGCAAACUCCCGU UCUCCG 23 7124

BCLllA-7055 + AGAAGCGCAAACUCCCGUUCUCCG 24 7125

BCLllA-7056 + GGCUGGGAGGGAGGAGGG 18 7126

BCLllA-7057 + GGGCUGGGAGGGAGGAGGG 19 7127

BCLllA-7058 + GGGGCUGGGAGGGAGGAGGG 20 7128

BCLllA-7059 + GGGGGCUGGGAGGGAGGAGGG 21 7129

BCLllA-7060 + CGGGGGCUGGGAGGGAGGAGGG 22 7130

BCLllA-7061 + CCGGGGGCUGGGAGGGAGGAGGG 23 7131

BCLllA-7062 + ACCGGGGGCUGGGAGGGAGGAGGG 24 7132

BCLllA-7063 + UGGUGGACUAAACAGGGG 18 7133

BCLllA-7064 + GUGGUGGACUAAACAGGGG 19 7134

BCLllA-6139 + GGUGGUGGACUAAACAGGGG 20 7135

BCLllA-7065 + CGGUGGUGGACUAAACAGGGG 21 7136

BCLllA-7066 + UCGGUGGUGGACUAAACAGGGG 22 7137

BCLllA-7067 + CUCGGUGGUGGACUAAACAGGGG 23 7138

BCLllA-7068 + UCUCGGUGGUGGACUAAACAGGGG 24 7139

BCLllA-7069 + AAGAGAAACCAUGCACUG 18 7140

BCLllA-7070 + CAAGAGAAACCAUGCACUG 19 7141

BCLllA-7071 + GCAAGAGAAACCAUGCACUG 20 7142

BCLllA-7072 + UGCAAGAGAAACCAUGCACUG 21 7143 BCLllA-7073 + UUGCAAGAGAAACCAUGCACUG 22 7144

BCLllA-7074 + GUUGCAAGAGAAACCAUGCACUG 23 7145

BCLllA-7075 + UGUUGCAAGAGAAACCAUGCACUG 24 7146

BCLllA-7076 + GUCAAAGGCACUCGGGUG 18 7147

BCLllA-7077 + UGUCAAAGGCACUCGGGUG 19 7148

BCLllA-7078 + CUGUCAAAGGCACUCGGGUG 20 7149

BCLllA-7079 + CCUGUCAAAGGCACUCGGGUG 21 7150

BCLllA-7080 + CCCUGUCAAAGGCACUCGGGUG 22 7151

BCLllA-7081 + ACCCUGUCAAAGGCACUCGGGUG 23 7152

BCLllA-7082 + CACCCUGUCAAAGGCACUCGGGUG 24 7153

BCLllA-7083 + CCCACCAAGUCGCUGGUG 18 7154

BCLllA-7084 + GCCCACCAAGUCGCUGGUG 19 7155

BCLllA-7085 + UGCCCACCAAGUCGCUGGUG 20 7156

BCLllA-7086 + CUGCCCACCAAGUCGCUGGUG 21 7157

BCLllA-7087 + GCUGCCCACCAAGUCGCUGGUG 22 7158

BCLllA-7088 + CGCUGCCCACCAAGUCGCUGGUG 23 7159

BCLllA-7089 + GCGCUGCCCACCAAGUCGCUGGUG 24 7160

BCLllA-7090 + GGGGUUAUUGUCUGCAAU 18 7161

BCLllA-7091 + AGGGGUUAUUGUCUGCAAU 19 7162

BCLllA-7092 + AAGGGGUUAUUGUCUGCAAU 20 7163

BCLllA-7093 + AAAGGGGUUAUUGUCUGCAAU 21 7164

BCLllA-7094 + UAAAGGGGUUAUUGUCUGCAAU 22 7165

BCLllA-7095 + UUAAAGGGGUUAUUGUCUGCAAU 23 7166

BCLllA-7096 + GUUAAAGGGGUUAUUGUCUGCAAU 24 7167

BCLllA-7097 + CUGGGUACUACGCCGAAU 18 7168

BCLllA-7098 + UCUGGGUACUACGCCGAAU 19 7169

BCLllA-6182 + CUCUGGGUACUACGCCGAAU 20 7170

BCLllA-7099 + UCUCUGGGUACUACGCCGAAU 21 7171

BCLllA-7100 + CUCUCUGGGUACUACGCCGAAU 22 7172

BCLllA-7101 + GCUCUCUGGGUACUACGCCGAAU 23 7173

BCLllA-7102 + AGCUCUCUGGGUACUACGCCGAAU 24 7174

BCLllA-7103 + CGUAGCCGGCGAGCCACU 18 7175

BCLllA-7104 + GCGUAGCCGGCGAGCCACU 19 7176

BCLllA-7105 + CGCGUAGCCGGCGAGCCACU 20 7177

BCLllA-7106 + CCGCGUAGCCGGCGAGCCACU 21 7178

BCLllA-7107 + GCCGCGUAGCCGGCGAGCCACU 22 7179

BCLllA-7108 + GGCCGCGUAGCCGGCGAGCCACU 23 7180

BCLllA-7109 + AGGCCGCGUAGCCGGCGAGCCACU 24 7181

BCLllA-7110 + CCACACAUCUUGAGCUCU 18 7182

BCLllA-7111 + GCCACACAUCUUGAGCUCU 19 7183

BCLllA-7112 + UGCCACACAUCUUGAGCUCU 20 7184

BCLllA-7113 + CUGCCACACAUCUUGAGCUCU 21 7185 BCLllA-7114 + ACUGCCACACAUCUUGAGCUCU 22 7186

BCLllA-7115 + AACUGCCACACAUCUUGAGCUCU 23 7187

BCLllA-7116 + AAACUGCCACACAUCUUGAGCUCU 24 7188

BCLllA-7117 + CGUUCUCCGGGAUCAGGU 18 7189

BCLllA-7118 + CCGUUCUCCGGGAUCAGGU 19 7190

BCLllA-6223 + CCCGUUCUCCGGGAUCAGGU 20 7191

BCLllA-7119 + CCCCGUUCUCCGGGAUCAGGU 21 7192

BCLllA-7120 + UCCCCGUUCUCCGGGAUCAGGU 22 7193

BCLllA-7121 + GUCCCCGUUCUCCGGGAUCAGGU 23 7194

BCLllA-7122 + CGUCCCCGUUCUCCGGGAUCAGGU 24 7195

BCLllA-7123 + CCAGGCGCUCUAUGCGGU 18 7196

BCLllA-7124 + CCCAGGCGCUCUAUGCGGU 19 7197

BCLllA-6226 + CCCCAGGCGCUCUAUGCGGU 20 7198

BCLllA-7125 + CCCCCAGGCGCUCUAUGCGGU 21 7199

BCLllA-7126 + GCCCCCAGGCGCUCUAUGCGGU 22 7200

BCLllA-7127 + CGCCCCCAGGCGCUCUAUGCGGU 23 7201

BCLllA-7128 + CCGCCCCCAGGCGCUCUAUGCGGU 24 7202

BCLllA-7129 - UUCCCAGCCACCUCUCCA 18 7203

BCLllA-7130 - CUUCCCAGCCACCUCUCCA 19 7204

BCLllA-5903 - CCUUCCCAGCCACCUCUCCA 20 7205

BCLllA-7131 - UCCUUCCCAGCCACCUCUCCA 21 7206

BCLllA-7132 - GUCCUUCCCAGCCACCUCUCCA 22 7207

BCLllA-7133 - UGUCCUUCCCAGCCACCUCUCCA 23 7208

BCLllA-7134 - AUGUCCUUCCCAGCCACCUCUCCA 24 7209

BCLllA-7135 - AGCGCAUCAAGCUCGAGA 18 7210

BCLllA-7136 - AAGCGCAUCAAGCUCGAGA 19 7211

BCLllA-5919 - UAAGCGCAUCAAGCUCGAGA 20 7212

BCLllA-7137 - CUAAGCGCAUCAAGCUCGAGA 21 7213

BCLllA-7138 - UCUAAGCGCAUCAAGCUCGAGA 22 7214

BCLllA-7139 - CUCUAAGCGCAUCAAGCUCGAGA 23 7215

BCLllA-7140 - UCUCUAAGCGCAUCAAGCUCGAGA 24 7216

BCLllA-7141 - GGAGCUGACGGAGAGCGA 18 7217

BCLllA-7142 - AGGAGCUGACGGAGAGCGA 19 7218

BCLllA-7143 - GAGGAGCUGACGGAGAGCGA 20 7219

BCLllA-7144 - GGAGGAGCUGACGGAGAGCGA 21 7220

BCLllA-7145 - AGGAGGAGCUGACGGAGAGCGA 22 7221

BCLllA-7146 - GAGGAGGAGCUGACGGAGAGCGA 23 7222

BCLllA-7147 - GGAGGAGGAGCUGACGGAGAGCGA 24 7223

BCLllA-7148 - UCACCCGAGUGCCU UUGA 18 7224

BCLllA-7149 - AUCACCCGAGUGCCUUUGA 19 7225

BCLllA-7150 - CAUCACCCGAGUGCCUU UGA 20 7226

BCLllA-7151 - CCAUCACCCGAGUGCCU UUGA 21 7227 BCLllA-7152 - CCCAUCACCCGAGUGCCUUUGA 22 7228

BCLllA-7153 - ACCCAUCACCCGAGUGCCUUUGA 23 7229

BCLllA-7154 - CACCCAUCACCCGAGUGCCUUUGA 24 7230

BCLllA-7155 - GAGCACUCCUCGGAGAAC 18 7231

BCLllA-7156 - GGAGCACUCCUCGGAGAAC 19 7232

BCLllA-5949 - CGGAGCACUCCUCGGAGAAC 20 7233

BCLllA-7157 - UCGGAGCACUCCUCGGAGAAC 21 7234

BCLllA-7158 - GUCGGAGCACUCCUCGGAGAAC 22 7235

BCLllA-7159 - CGUCGGAGCACUCCUCGGAGAAC 23 7236

BCLllA-7160 - UCGUCGGAGCACUCCUCGGAGAAC 24 7237

BCLllA-7161 - GCCCUGGCCACCCAUCAC 18 7238

BCLllA-7162 - GGCCCUGGCCACCCAUCAC 19 7239

BCLllA-7163 - UGGCCCUGGCCACCCAUCAC 20 7240

BCLllA-7164 - AUGGCCCUGGCCACCCAUCAC 21 7241

BCLllA-7165 - GAUGGCCCUGGCCACCCAUCAC 22 7242

BCLllA-7166 - AGAUGGCCCUGGCCACCCAUCAC 23 7243

BCLllA-7167 - GAGAUGGCCCUGGCCACCCAUCAC 24 7244

BCLllA-7168 - U U AACCUGCU AAGAAU AC 18 7245

BCLllA-7169 - UUUAACCUGCUAAGAAUAC 19 7246

BCLllA-7170 - CUUUAACCUGCUAAGAAUAC 20 7247

BCLllA-7171 - CCUUUAACCUGCUAAGAAUAC 21 7248

BCLllA-7172 - CCCUUUAACCUGCUAAGAAUAC 22 7249

BCLllA-7173 - CCCCUUUAACCUGCUAAGAAUAC 23 7250

BCLllA-7174 - ACCCCUUUAACCUGCUAAGAAUAC 24 7251

BCLllA-7175 - CGGAAGUCCCCUGACCCC 18 7252

BCLllA-7176 - ACGGAAGUCCCCUGACCCC 19 7253

BCLllA-7177 - CACGGAAGUCCCCUGACCCC 20 7254

BCLllA-7178 - ACACGGAAGUCCCCUGACCCC 21 7255

BCLllA-7179 - AACACGGAAGUCCCCUGACCCC 22 7256

BCLllA-7180 - GAACACGGAAGUCCCCUGACCCC 23 7257

BCLllA-7181 - CGAA CACGGAAGUCCCCUGACCCC 24 7258

BCLllA-7182 - AGAAAAUUUGAAGCCCCC 18 7259

BCLllA-7183 - G AG AAAAU U UG AAG CCCCC 19 7260

BCLllA-5969 - UGAGAAAAUUUGAAGCCCCC 20 7261

BCLllA-7184 - CUGAGAAAAUUUGAAGCCCCC 21 7262

BCLllA-7185 - UCUGAGAAAAUUUGAAGCCCCC 22 7263

BCLllA-7186 - UUCUGAGAAAAUUUGAAGCCCCC 23 7264

BCLllA-7187 - GUUCUGAGAAAAUUUGAAGCCCCC 24 7265

BCLllA-7188 - GCUAUGGAGCCUCCCGCC 18 7266

BCLllA-7189 - GGCUAUGGAGCCUCCCGCC 19 7267

BCLllA-7190 - UGGCUAUGGAGCCUCCCGCC 20 7268

BCLllA-7191 - AUGGCUAUGGAGCCUCCCGCC 21 7269 BCLllA-7192 - AAUGGCUAUGGAGCCUCCCGCC 22 7270

BCLllA-7193 - CAAUGGCUAUGGAGCCUCCCGCC 23 7271

BCLllA-7194 - CCAAUGGCUAUGGAGCCUCCCGCC 24 7272

BCLllA-7195 - AACACG CACAG AACACU C 18 7273

BCLllA-7196 - CAACACGCACAGAACACUC 19 7274

BCLllA-7197 - GCAACACGCACAGAACACUC 20 7275

BCLllA-7198 - U G CAAC ACG CAC AG AAC AC U C 21 7276

BCLllA-7199 - UUGCAACACGCACAGAACACUC 22 7277

BCLllA-7200 - C U U G CAAC ACG CACAG AAC ACU C 23 7278

BCLllA-7201 - UCUUGCAACACGCACAGAACACUC 24 7279

BCLllA-7202 - ACGAAGACUCGGUGGCCG 18 7280

BCLllA-7203 - GACGAAGACUCGGUGGCCG 19 7281

BCLllA-7204 - CGACGAAGACUCGGUGGCCG 20 7282

BCLllA-7205 - GCGACGAAGACUCGGUGGCCG 21 7283

BCLllA-7206 - UGCGACGAAGACUCGGUGGCCG 22 7284

BCLllA-7207 - UUGCGACGAAGACUCGGUGGCCG 23 7285

BCLllA-7208 - CUUGCGACGAAGACUCGGUGGCCG 24 7286

BCLllA-7209 - GCCCGGGGAGCUGGACGG 18 7287

BCLllA-7210 - CGCCCGGGGAGCUGGACGG 19 7288

BCLllA-6121 - CCGCCCGGGGAGCUGGACGG 20 7289

BCLllA-7211 - ACCGCCCGGGGAGCUGGACGG 21 7290

BCLllA-7212 - CACCGCCCGGGGAGCUGGACGG 22 7291

BCLllA-7213 - ACACCGCCCGGGGAGCUGGACGG 23 7292

BCLllA-7214 - CACACCGCCCGGGGAGCUGGACGG 24 7293

BCLllA-7215 - GCCGCGGCUGCUCCCCGG 18 7294

BCLllA-7216 - GGCCGCGGCUGCUCCCCGG 19 7295

BCLllA-7217 - UGGCCGCGGCUGCUCCCCGG 20 7296

BCLllA-7218 - AUGGCCGCGGCUGCUCCCCGG 21 7297

BCLllA-7219 - AAUGGCCGCGGCUGCUCCCCGG 22 7298

BCLllA-7220 - UAAUGGCCGCGGCUGCUCCCCGG 23 7299

BCLllA-7221 - UUAAUGGCCGCGGCUGCUCCCCGG 24 7300

BCLllA-7222 - UUUGACAGGGUGCUGCGG 18 7301

BCLllA-7223 - CUUUGACAGGGUGCUGCGG 19 7302

BCLllA-7224 - CCUUUGACAGGGUGCUGCGG 20 7303

BCLllA-7225 - GCCUUUGACAGGGUGCUGCGG 21 7304

BCLllA-7226 - UGCCUUUGACAGGGUGCUGCGG 22 7305

BCLllA-7227 - GUGCCUUUGACAGGGUGCUGCGG 23 7306

BCLllA-7228 - AGUGCCUUUGACAGGGUGCUGCGG 24 7307

BCLllA-7229 - AUUUGAAGCCCCCAGGGG 18 7308

BCLllA-7230 - AAUUUGAAGCCCCCAGGGG 19 7309

BCLllA-6140 - AAAUUUGAAGCCCCCAGGGG 20 7310

BCLllA-7231 - AAAAUUUGAAGCCCCCAGGGG 21 7311 BCLllA-7232 - GAAAAUUUGAAGCCCCCAGGGG 22 7312

BCLllA-7233 - AGAAAAUUUGAAGCCCCCAGGGG 23 7313

BCLllA-7234 - GAGAAAAUUUGAAGCCCCCAGGGG 24 7314

BCLllA-7235 - UCCCUUCAGGACUAGGUG 18 7315

BCLllA-7236 - AUCCCUUCAGGACUAGGUG 19 7316

BCLllA-7237 - UAUCCCUUCAGGACUAGGUG 20 7317

BCLllA-7238 - GUAUCCCUUCAGGACUAGGUG 21 7318

BCLllA-7239 - GGUAUCCCUUCAGGACUAGGUG 22 7319

BCLllA-7240 - UGGUAUCCCUUCAGGACUAGGUG 23 7320

BCLllA-7241 - UUGGUAUCCCUUCAGGACUAGGUG 24 7321

BCLllA-7242 - CGGUCAAGUCCAAGUCAU 18 7322

BCLllA-7243 - CCGG U CAAG U CCAAG U CAU 19 7323

BCLllA-7244 - CCCGGUCAAGUCCAAGUCAU 20 7324

BCLllA-7245 - CCCCGGUCAAGUCCAAGUCAU 21 7325

BCLllA-7246 - CCCCCGGUCAAGUCCAAGUCAU 22 7326

BCLllA-7247 - GCCCCCGGUCAAGUCCAAGUCAU 23 7327

BCLllA-7248 - AGCCCCCGGUCAAGUCCAAGUCAU 24 7328

BCLllA-7249 - UAACCCCUUUAACCUGCU 18 7329

BCLllA-7250 - AUAACCCCUUUAACCUGCU 19 7330

BCLllA-7251 - AAUAACCCCUUUAACCUGCU 20 7331

BCLllA-7252 - CAAUAACCCCUUUAACCUGCU 21 7332

BCLllA-7253 - ACAAUAACCCCUUUAACCUGCU 22 7333

BCLllA-7254 - GACAAUAACCCCUUUAACCUGCU 23 7334

BCLllA-7255 - AGACAAUAACCCCUUUAACCUGCU 24 7335

BCLllA-7256 - ACAGAACACUCAUGGAUU 18 7336

BCLllA-7257 - CACAGAACACUCAUGGAUU 19 7337

BCLllA-7258 - GCACAGAACACUCAUGGAUU 20 7338

BCLllA-7259 - CGCACAGAACACUCAUGGAUU 21 7339

BCLllA-7260 - ACGCACAGAACACUCAUGGAUU 22 7340

BCLllA-7261 - CACGCACAG AACACU CAUGG AUU 23 7341

BCLllA-7262 - ACACG CACAG AACACU CAUGG AU U 24 7342

BCLllA-7263 - GCAGACGCAGCGACACUU 18 7343

BCLllA-7264 - GGCAGACGCAGCGACACUU 19 7344

BCLllA-7265 - GGGCAGACGCAGCGACACUU 20 7345

BCLllA-7266 - AGGGCAGACGCAGCGACACUU 21 7346

BCLllA-7267 - GAGGGCAGACGCAGCGACACUU 22 7347

BCLllA-7268 - AGAGGGCAGACGCAGCGACACUU 23 7348

BCLllA-7269 - AAGAGGGCAGACGCAGCGACACUU 24 7349

BCLllA-7270 - CAAGAUGUGUGGCAGUUU 18 7350

BCLllA-7271 - UCAAGAUGUGUGGCAGUUU 19 7351

BCLllA-7272 - CUCAAGAUGUGUGGCAGUUU 20 7352

BCLllA-7273 - GCUCAAGAUGUGUGGCAGUUU 21 7353 BCLllA-7274 - AGCUCAAGAUGUGUGGCAGUUU 22 7354

BCLllA-7275 - GAGCUCAAGAUGUGUGGCAGUUU 23 7355

BCLllA-7276 - AGAGCUCAAGAUGUGUGGCAGUUU 24 7356

Table 13E provides exemplary targeting domains for knocking out the BCL11A 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), and the 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 13E

BCLllA-5892 + UCUCGGUGGUGGACUAAACA 20 7380

BCLllA-7299 + GUCUCGGUGGUGGACUAAACA 21 7381

BCLllA-7300 + UGUCUCGGUGGUGGACUAAACA 22 7382

BCLllA-7301 + AUGUCUCGGUGGUGGACUAAACA 23 7383

BCLllA-7302 + GAUGUCUCGGUGGUGGACUAAACA 24 7384

BCLllA-7303 + AG AAAG AGG U UGG AG ACA 18 7385

BCLllA-7304 + UAGAAAGAGGUUGGAGACA 19 7386

BCLllA-7305 + CU AG AAAG AGG U UGG AG ACA 20 7387

BCLllA-7306 + CCUAGAAAGAGGUUGGAGACA 21 7388

BCLllA-7307 + ACCUAGAAAGAGGUUGGAGACA 22 7389

BCLllA-7308 + AACCUAGAAAGAGGUUGGAGACA 23 7390

BCLllA-7309 + GAACCUAGAAAGAGGUUGGAGACA 24 7391

BCLllA-7310 + UCUGCAAUAUGAAUCCCA 18 7392

BCLllA-7311 + GUCUGCAAUAUGAAUCCCA 19 7393

BCLllA-5899 + UGUCUGCAAUAUGAAUCCCA 20 7394

BCLllA-7312 + UUGUCUGCAAUAUGAAUCCCA 21 7395

BCLllA-7313 + AUUGUCUGCAAUAUGAAUCCCA 22 7396

BCLllA-7314 + UAUUGUCUGCAAUAUGAAUCCCA 23 7397

BCLllA-7315 + UUAUUGUCUGCAAUAUGAAUCCCA 24 7398

BCLllA-7316 + CCUCGCUGAAGUGCUGCA 18 7399

BCLllA-7317 + GCCUCGCUGAAGUGCUGCA 19 7400

BCLllA-5909 + GGCCUCGCUGAAGUGCUGCA 20 7401

BCLllA-7318 + AGGCCUCGCUGAAGUGCUGCA 21 7402

BCLllA-7319 + AAGGCCUCGCUGAAGUGCUGCA 22 7403

BCLllA-7320 + GAAGGCCUCGCUGAAGUGCUGCA 23 7404

BCLllA-7321 + GGAAGGCCUCGCUGAAGUGCUGCA 24 7405

BCLllA-7322 + GAGGAGGGGCGGAUUGCA 18 7406

BCLllA-7323 + GGAGGAGGGGCGGAUUGCA 19 7407

BCLllA-7324 + GGGAGGAGGGGCGGAU UGCA 20 7408

BCLllA-7325 + AGGGAGGAGGGGCGGAUUGCA 21 7409

BCLllA-7326 + GAGGGAGGAGGGGCGGAUUGCA 22 7410

BCLllA-7327 + GGAGGGAGGAGGGGCGGAUUGCA 23 7411

BCLllA-7328 + GGGAGGGAGGAGGGGCGGAUUGCA 24 7412

BCLllA-7329 + GUUGCAGUAACCUUUGCA 18 7413

BCLllA-7330 + GGU UGCAGUAACCUUUGCA 19 7414

BCLllA-7331 + UGGUUGCAGUAACCUUUGCA 20 7415

BCLllA-7332 + AUGGUUGCAGUAACCU UUGCA 21 7416

BCLllA-7333 + AAUGGUUGCAGUAACCU UUGCA 22 7417

BCLllA-7334 + GAAUGGUUGCAGUAACCUUUGCA 23 7418

BCLllA-7335 + GGAAUGGUUGCAGUAACCUUUGCA 24 7419

BCLllA-7336 + GCUUAGAGAAGGGGCUCA 18 7420

BCLllA-7337 + CGCUUAGAGAAGGGGCUCA 19 7421 BCLllA-7338 + GCGCUUAGAGAAGGGGCUCA 20 7422

BCLllA-7339 + UGCGCUUAGAGAAGGGGCUCA 21 7423

BCLllA-7340 + AUGCGCUUAGAGAAGGGGCUCA 22 7424

BCLllA-7341 + GAUGCGCUUAGAGAAGGGGCUCA 23 7425

BCLllA-7342 + UGAUGCGCUUAGAGAAGGGGCUCA 24 7426

BCLllA-7343 + CGUCGGACUUGACCGUCA 18 7427

BCLllA-7344 + UCGUCGGACUUGACCGUCA 19 7428

BCLllA-5912 + GUCGUCGGACUUGACCGUCA 20 7429

BCLllA-7345 + CGUCGUCGGACUUGACCGUCA 21 7430

BCLllA-7346 + CCGUCGUCGGACU UGACCGUCA 22 7431

BCLllA-7347 + ACCGUCGUCGGACUUGACCGUCA 23 7432

BCLllA-7348 + GACCGUCGUCGGACUUGACCGUCA 24 7433

BCLllA-7349 + UACCAACCCGCGGGGUCA 18 7434

BCLllA-7350 + AUACCAACCCGCGGGGUCA 19 7435

BCLllA-5913 + GAUACCAACCCGCGGGGUCA 20 7436

BCLllA-7351 + GGAUACCAACCCGCGGGGUCA 21 7437

BCLllA-7352 + GGGAUACCAACCCGCGGGGUCA 22 7438

BCLllA-7353 + AGGGAUACCAACCCGCGGGGUCA 23 7439

BCLllA-7354 + AAGGGAUACCAACCCGCGGGGUCA 24 7440

BCLllA-7355 + GCUUGAUGCGCUUAGAGA 18 7441

BCLllA-7356 + AGCUUGAUGCGCUUAGAGA 19 7442

BCLllA-5917 + GAGCUUGAUGCGCUUAGAGA 20 7443

BCLllA-7357 + CGAGCU UGAUGCGCUUAGAGA 21 7444

BCLllA-7358 + UCGAGCUUGAUGCGCUUAGAGA 22 7445

BCLllA-7359 + CUCGAGCU UGAUGCGCU UAGAGA 23 7446

BCLllA-7360 + UCUCGAGCUUGAUGCGCUUAGAGA 24 7447

BCLllA-7361 + CUAGAAAGAGGUUGGAGA 18 7448

BCLllA-7362 + CCUAGAAAGAGGUUGGAGA 19 7449

BCLllA-7363 + ACCUAGAAAGAGGUUGGAGA 20 7450

BCLllA-7364 + AACCUAGAAAGAGGUUGGAGA 21 7451

BCLllA-7365 + GAACCUAGAAAGAGGUUGGAGA 22 7452

BCLllA-7366 + AGAACCUAGAAAGAGGUUGGAGA 23 7453

BCLllA-7367 + AAGAACCUAGAAAGAGGUUGGAGA 24 7454

BCLllA-7368 + GUGUGUGAAGAACCUAGA 18 7455

BCLllA-7369 + GGUGUGUGAAGAACCUAGA 19 7456

BCLllA-7370 + GGGUGUGUGAAGAACCUAGA 20 7457

BCLllA-7371 + GGGGUGUGUGAAGAACCUAGA 21 7458

BCLllA-7372 + GGGGGUGUGUGAAGAACCUAGA 22 7459

BCLllA-7373 + UGGGGGUGUGUGAAGAACCUAGA 23 7460

BCLllA-7374 + AUGGGGGUGUGUGAAGAACCUAGA 24 7461

BCLllA-7375 + CUCUGGGUACUACGCCGA 18 7462

BCLllA-7376 + UCUCUGGGUACUACGCCGA 19 7463 BCLllA-7377 + CUCUCUGGGUACUACGCCGA 20 7464

BCLllA-7378 + GCUCUCUGGGUACUACGCCGA 21 7465

BCLllA-7379 + AGCUCUCUGGGUACUACGCCGA 22 7466

BCLllA-7380 + GAGCUCUCUGGGUACUACGCCGA 23 7467

BCLllA-7381 + UGAGCUCUCUGGGUACUACGCCGA 24 7468

BCLllA-7382 + GAGGUUGGAGACAGAGGA 18 7469

BCLllA-7383 + AGAGGUUGGAGACAGAGGA 19 7470

BCLllA-5925 + AAGAGGUUGGAGACAGAGGA 20 7471

BCLllA-7384 + AAAGAGGUUGGAGACAGAGGA 21 7472

BCLllA-7385 + GAAAGAGGUUGGAGACAGAGGA 22 7473

BCLllA-7386 + AGAAAGAGGUUGGAGACAGAGGA 23 7474

BCLllA-7387 + UAGAAAGAGGUUGGAGACAGAGGA 24 7475

BCLllA-7388 + GGGGCGGAUUGCAGAGGA 18 7476

BCLllA-7389 + AGGGGCGGAUUGCAGAGGA 19 7477

BCLllA-5926 + GAGGGGCGGAUUGCAGAGGA 20 7478

BCLllA-7390 + GGAGGGGCGGAUUGCAGAGGA 21 7479

BCLllA-7391 + AGGAGGGGCGGAUUGCAGAGGA 22 7480

BCLllA-7392 + GAGGAGGGGCGGAUUGCAGAGGA 23 7481

BCLllA-7393 + GGAGGAGGGGCGGAUUGCAGAGGA 24 7482

BCLllA-7394 + CGGAUUGCAGAGGAGGGA 18 7483

BCLllA-7395 + GCGGAUUGCAGAGGAGGGA 19 7484

BCLllA-5930 + GGCGGAUUGCAGAGGAGGGA 20 7485

BCLllA-7396 + GGGCGGAUUGCAGAGGAGGGA 21 7486

BCLllA-7397 + GGGGCGGAUUGCAGAGGAGGGA 22 7487

BCLllA-7398 + AGGGGCGGAUUGCAGAGGAGGGA 23 7488

BCLllA-7399 + GAGGGGCGGAUUGCAGAGGAGGGA 24 7489

BCLllA-7400 + CUUGACCGGGGGCUGGGA 18 7490

BCLllA-7401 + ACU UGACCGGGGGCUGGGA 19 7491

BCLllA-5931 + GACUUGACCGGGGGCUGGGA 20 7492

BCLllA-7402 + GGACUUGACCGGGGGCUGGGA 21 7493

BCLllA-7403 + UGGACUUGACCGGGGGCUGGGA 22 7494

BCLllA-7404 + U UGGACUUGACCGGGGGCUGGGA 23 7495

BCLllA-7405 + CUUGGACUUGACCGGGGGCUGGGA 24 7496

BCLllA-7406 + CGCAUGACUUGGACUUGA 18 7497

BCLllA-7407 + UCGCAUGACU UGGACU UGA 19 7498

BCLllA-7408 + CUCGCAUGACUUGGACUUGA 20 7499

BCLllA-7409 + ACUCGCAUGACUUGGACUUGA 21 7500

BCLllA-7410 + AACUCGCAUGACU UGGACUUGA 22 7501

BCLllA-7411 + GAACUCGCAUGACUUGGACUUGA 23 7502

BCLllA-7412 + AGAACUCGCAUGACUUGGACUUGA 24 7503

BCLllA-7413 + GGGCCCGGACCACUAAUA 18 7504

BCLllA-7414 + CGGGCCCGGACCACUAAUA 19 7505 BCLllA-5940 + CCGGGCCCGGACCACUAAUA 20 7506

BCLllA-7415 + CCCGGGCCCGGACCACUAAUA 21 7507

BCLllA-7416 + GCCCGGGCCCGGACCACUAAUA 22 7508

BCLllA-7417 + UGCCCGGGCCCGGACCACUAAUA 23 7509

BCLllA-7418 + CUGCCCGGGCCCGGACCACUAAUA 24 7510

BCLllA-7419 + AGCUCUCUAAGUCUCCUA 18 7511

BCLllA-7420 + CAGCUCUCUAAGUCUCCUA 19 7512

BCLllA-7421 + CCAGCUCUCUAAGUCUCCUA 20 7513

BCLllA-7422 + GCCAGCUCUCUAAGUCUCCUA 21 7514

BCLllA-7423 + UGCCAGCUCUCUAAGUCUCCUA 22 7515

BCLllA-7424 + CUGCCAGCUCUCUAAGUCUCCUA 23 7516

BCLllA-7425 + CCUGCCAGCUCUCUAAGUCUCCUA 24 7517

BCLllA-7426 + CUGGAGUCUCCGAAGCUA 18 7518

BCLllA-7427 + UCUGGAGUCUCCGAAGCUA 19 7519

BCLllA-5943 + GUCUGGAGUCUCCGAAGCUA 20 7520

BCLllA-7428 + UGUCUGGAGUCUCCGAAGCUA 21 7521

BCLllA-7429 + U UGUCUGGAGUCUCCGAAGCUA 22 7522

BCLllA-7430 + AUUGUCUGGAGUCUCCGAAGCUA 23 7523

BCLllA-7431 + GAUUGUCUGGAGUCUCCGAAGCUA 24 7524

BCLllA-7432 + UCGAGCUUGAUGCGCU UA 18 7525

BCLllA-7433 + CUCGAGCU UGAUGCGCUUA 19 7526

BCLllA-7434 + UCUCGAGCUUGAUGCGCUUA 20 7527

BCLllA-7435 + U UCUCGAGCUUGAUGCGCUUA 21 7528

BCLllA-7436 + CUUCUCGAGCUUGAUGCGCUUA 22 7529

BCLllA-7437 + CCUUCUCGAGCUUGAUGCGCUUA 23 7530

BCLllA-7438 + UCCUUCUCGAGCU UGAUGCGCUUA 24 7531

BCLllA-7439 + GGUAUUCUUAGCAGGU UA 18 7532

BCLllA-7440 + UGGUAUUCUUAGCAGGUUA 19 7533

BCLllA-7441 + CUGGUAUUCUUAGCAGGUUA 20 7534

BCLllA-7442 + CCUGGUAUUCUUAGCAGGUUA 21 7535

BCLllA-7443 + UCCUGGUAUUCUUAGCAGGUUA 22 7536

BCLllA-7444 + AUCCUGGUAUUCUUAGCAGGUUA 23 7537

BCLllA-7445 + GAUCCUGGUAUUCUUAGCAGGUUA 24 7538

BCLllA-7446 + CUCGGUGGUGGACUAAAC 18 7539

BCLllA-7447 + UCUCGGUGGUGGACUAAAC 19 7540

BCLllA-5947 + GUCUCGGUGGUGGACUAAAC 20 7541

BCLllA-7448 + UGUCUCGGUGGUGGACUAAAC 21 7542

BCLllA-7449 + AUGUCUCGGUGGUGGACUAAAC 22 7543

BCLllA-7450 + GAUGUCUCGGUGGUGGACUAAAC 23 7544

BCLllA-7451 + UGAUGUCUCGGUGGUGGACUAAAC 24 7545

BCLllA-7452 + UCCGAGGAGUGCUCCGAC 18 7546

BCLllA-7453 + CUCCGAGGAGUGCUCCGAC 19 7547 BCLllA-7454 + UCUCCGAGGAGUGCUCCGAC 20 7548

BCLllA-7455 + UUCUCCGAGGAGUGCUCCGAC 21 7549

BCLllA-7456 + GUUCUCCGAGGAGUGCUCCGAC 22 7550

BCLllA-7457 + CGUUCUCCGAGGAGUGCUCCGAC 23 7551

BCLllA-7458 + CCGUUCUCCGAGGAGUGCUCCGAC 24 7552

BCLllA-7459 + AACUUGGCCACCACGGAC 18 7553

BCLllA-7460 + GAACUUGGCCACCACGGAC 19 7554

BCLllA-7461 + UGAACUUGGCCACCACGGAC 20 7555

BCLllA-7462 + U UGAACUUGGCCACCACGGAC 21 7556

BCLllA-7463 + CUUGAACUUGGCCACCACGGAC 22 7557

BCLllA-7464 + UCUUGAACUUGGCCACCACGGAC 23 7558

BCLllA-7465 + CUCU UGAACUUGGCCACCACGGAC 24 7559

BCLllA-7466 + CCGCAGAACUCGCAUGAC 18 7560

BCLllA-7467 + GCCGCAGAACUCGCAUGAC 19 7561

BCLllA-7468 + UGCCGCAGAACUCGCAUGAC 20 7562

BCLllA-7469 + U UGCCGCAGAACUCGCAUGAC 21 7563

BCLllA-7470 + CUUGCCGCAGAACUCGCAUGAC 22 7564

BCLllA-7471 + UCUUGCCGCAGAACUCGCAUGAC 23 7565

BCLllA-7472 + GUCUUGCCGCAGAACUCGCAUGAC 24 7566

BCLllA-7473 + GCAUGACUUGGACUUGAC 18 7567

BCLllA-7474 + CGCAUGACUUGGACUUGAC 19 7568

BCLllA-5957 + UCGCAUGACU UGGACU UGAC 20 7569

BCLllA-7475 + CUCGCAUGACUUGGACU UGAC 21 7570

BCLllA-7476 + ACUCGCAUGACUUGGACUUGAC 22 7571

BCLllA-7477 + AACUCGCAUGACU UGGACUUGAC 23 7572

BCLllA-7478 + GAACUCGCAUGACUUGGACUUGAC 24 7573

BCLllA-7479 + GGGGGUGUGUGAAGAACC 18 7574

BCLllA-7480 + UGGGGGUGUGUGAAGAACC 19 7575

BCLllA-7481 + AUGGGGGUGUGUGAAGAACC 20 7576

BCLllA-7482 + AAUGGGGGUGUGUGAAGAACC 21 7577

BCLllA-7483 + GAAUGGGGGUGUGUGAAGAACC 22 7578

BCLllA-7484 + CGAAUGGGGGUGUGUGAAGAACC 23 7579

BCLllA-7485 + CCGAAUGGGGGUGUGUGAAGAACC 24 7580

BCLllA-7486 + CUCU UGAACUUGGCCACC 18 7581

BCLllA-7487 + GCUCU UGAACUUGGCCACC 19 7582

BCLllA-7488 + CGCUCU UGAACUUGGCCACC 20 7583

BCLllA-7489 + UCGCUCUUGAACUUGGCCACC 21 7584

BCLllA-7490 + CUCGCUCUUGAACU UGGCCACC 22 7585

BCLllA-7491 + UCUCGCUCUUGAACUUGGCCACC 23 7586

BCLllA-7492 + UUCUCGCUCUUGAACUUGGCCACC 24 7587

BCLllA-7493 + CAUGACUUGGACUUGACC 18 7588

BCLllA-7494 + GCAUGACUUGGACUUGACC 19 7589 BCLllA-5965 + CGCAUGACUUGGACUUGACC 20 7590

BCLllA-7495 + UCGCAUGACUUGGACUUGACC 21 7591

BCLllA-7496 + CUCGCAUGACUUGGACUUGACC 22 7592

BCLllA-7497 + ACUCGCAUGACUUGGACUUGACC 23 7593

BCLllA-7498 + AACUCGCAUGACUUGGACUUGACC 24 7594

BCLllA-7499 + CUGAAGGGAUACCAACCC 18 7595

BCLllA-7500 + CCUGAAGGGAUACCAACCC 19 7596

BCLllA-7501 + UCCUGAAGGGAUACCAACCC 20 7597

BCLllA-7502 + GUCCUGAAGGGAUACCAACCC 21 7598

BCLllA-7503 + AGUCCUGAAGGGAUACCAACCC 22 7599

BCLllA-7504 + UAGUCCUGAAGGGAUACCAACCC 23 7600

BCLllA-7505 + CUAGUCCUGAAGGGAUACCAACCC 24 7601

BCLllA-7506 + CGCCCACGACCGCGCCCC 18 7602

BCLllA-7507 + ACGCCCACGACCGCGCCCC 19 7603

BCLllA-3830 + CACGCCCACGACCGCGCCCC 20 7604

BCLllA-7508 + CCACGCCCACGACCGCGCCCC 21 7605

BCLllA-7509 + CCCACGCCCACGACCGCGCCCC 22 7606

BCLllA-7510 + GCCCACGCCCACGACCGCGCCCC 23 7607

BCLllA-7511 + CGCCCACGCCCACGACCGCGCCCC 24 7608

BCLllA-7512 + GCUUUUUGGACAGGCCCC 18 7609

BCLllA-7513 + AGCUUUUUGGACAGGCCCC 19 7610

BCLllA-7514 + CAGCU UUUUGGACAGGCCCC 20 7611

BCLllA-7515 + GCAGCU UUUUGGACAGGCCCC 21 7612

BCLllA-7516 + AGCAGCUUUUUGGACAGGCCCC 22 7613

BCLllA-7517 + CAGCAGCUUU UUGGACAGGCCCC 23 7614

BCLllA-7518 + GCAGCAGCUUU UUGGACAGGCCCC 24 7615

BCLllA-7519 + CCCGAGGCCGACUCGCCC 18 7616

BCLllA-7520 + CCCCGAGGCCGACUCGCCC 19 7617

BCLllA-5977 + CCCCCGAGGCCGACUCGCCC 20 7618

BCLllA-7521 + CCCCCCGAGGCCGACUCGCCC 21 7619

BCLllA-7522 + GCCCCCCGAGGCCGACUCGCCC 22 7620

BCLllA-7523 + GGCCCCCCGAGGCCGACUCGCCC 23 7621

BCLllA-7524 + AGGCCCCCCGAGGCCGACUCGCCC 24 7622

BCLllA-7525 + GUCUGCAAUAUGAAUCCC 18 7623

BCLllA-7526 + UGUCUGCAAUAUGAAUCCC 19 7624

BCLllA-7527 + U UGUCUGCAAUAUGAAUCCC 20 7625

BCLllA-7528 + AUUGUCUGCAAUAUGAAUCCC 21 7626

BCLllA-7529 + UAUUGUCUGCAAUAUGAAUCCC 22 7627

BCLllA-7530 + U UAUUGUCUGCAAUAUGAAUCCC 23 7628

BCLllA-7531 + GU UAUUGUCUGCAAUAUGAAUCCC 24 7629

BCLllA-7532 + UUCCCGUGCCGCUGCGCC 18 7630

BCLllA-7533 + CUUCCCGUGCCGCUGCGCC 19 7631 BCLllA-7534 + ACUUCCCGUGCCGCUGCGCC 20 7632

BCLllA-7535 + CACUUCCCGUGCCGCUGCGCC 21 7633

BCLllA-7536 + CCACUUCCCGUGCCGCUGCGCC 22 7634

BCLllA-7537 + UCCACUUCCCGUGCCGCUGCGCC 23 7635

BCLllA-7538 + CUCCACUUCCCGUGCCGCUGCGCC 24 7636

BCLllA-7539 + CCCCGAGGCCGACUCGCC 18 7637

BCLllA-7540 + CCCCCGAGGCCGACUCGCC 19 7638

BCLllA-5989 + CCCCCCGAGGCCGACUCGCC 20 7639

BCLllA-7541 + GCCCCCCGAGGCCGACUCGCC 21 7640

BCLllA-7542 + GGCCCCCCGAGGCCGACUCGCC 22 7641

BCLllA-7543 + AGGCCCCCCGAGGCCGACUCGCC 23 7642

BCLllA-7544 + CAGGCCCCCCGAGGCCGACUCGCC 24 7643

BCLllA-7545 + GCGCUUAUGCUUCUCGCC 18 7644

BCLllA-7546 + CGCGCUUAUGCUUCUCGCC 19 7645

BCLllA-7547 + CCGCGCUUAUGCUUCUCGCC 20 7646

BCLllA-7548 + GCCGCGCUUAUGCUUCUCGCC 21 7647

BCLllA-7549 + GGCCGCGCUUAUGCUUCUCGCC 22 7648

BCLllA-7550 + UGGCCGCGCUUAUGCUUCUCGCC 23 7649

BCLllA-7551 + GUGGCCGCGCUUAUGCUUCUCGCC 24 7650

BCLllA-7552 + GGGAGGGGGGGCGUCGCC 18 7651

BCLllA-7553 + AGGGAGGGGGGGCGUCGCC 19 7652

BCLllA-5990 + GAGGGAGGGGGGGCGUCGCC 20 7653

BCLllA-7554 + GGAGGGAGGGGGGGCGUCGCC 21 7654

BCLllA-7555 + AGGAGGGAGGGGGGGCGUCGCC 22 7655

BCLllA-7556 + GAGGAGGGAGGGGGGGCGUCGCC 23 7656

BCLllA-7557 + AGAGGAGGGAGGGGGGGCGUCGCC 24 7657

BCLllA-7558 + CAUAGGGCUGGGCCGGCC 18 7658

BCLllA-7559 + GCAUAGGGCUGGGCCGGCC 19 7659

BCLllA-5991 + UGCAUAGGGCUGGGCCGGCC 20 7660

BCLllA-7560 + UUGCAUAGGGCUGGGCCGGCC 21 7661

BCLllA-7561 + UUUGCAUAGGGCUGGGCCGGCC 22 7662

BCLllA-7562 + CUUUGCAUAGGGCUGGGCCGGCC 23 7663

BCLllA-7563 + CCUUUGCAUAGGGCUGGGCCGGCC 24 7664

BCLllA-7564 + GUGUUGGGCAUCGCGGCC 18 7665

BCLllA-7565 + CGUGUUGGGCAUCGCGGCC 19 7666

BCLllA-5993 + CCGUGU UGGGCAUCGCGGCC 20 7667

BCLllA-7566 + UCCGUGUUGGGCAUCGCGGCC 21 7668

BCLllA-7567 + CUCCGUGU UGGGCAUCGCGGCC 22 7669

BCLllA-7568 + UCUCCGUGUUGGGCAUCGCGGCC 23 7670

BCLllA-7569 + UUCUCCGUGUUGGGCAUCGCGGCC 24 7671

BCLllA-7570 + AGGGAUCUUUGAGCUGCC 18 7672

BCLllA-7571 + AAGGGAUCUUUGAGCUGCC 19 7673 BCLllA-6000 + GAAGGGAUCUUUGAGCUGCC 20 7674

BCLllA-7572 + GGAAGGGAUCUUUGAGCUGCC 21 7675

BCLllA-7573 + AGGAAGGGAUCUUUGAGCUGCC 22 7676

BCLllA-7574 + AAGGAAGGGAUCUUUGAGCUGCC 23 7677

BCLllA-7575 + UAAGGAAGGGAUCUUUGAGCUGCC 24 7678

BCLllA-7576 + AUCCCUCCGUCCAGCUCC 18 7679

BCLllA-7577 + GAUCCCUCCGUCCAGCUCC 19 7680

BCLllA-7578 + AGAUCCCUCCGUCCAGCUCC 20 7681

BCLllA-7579 + GAGAUCCCUCCGUCCAGCUCC 21 7682

BCLllA-7580 + CGAGAUCCCUCCGUCCAGCUCC 22 7683

BCLllA-7581 + CCGAGAUCCCUCCGUCCAGCUCC 23 7684

BCLllA-7582 + CCCGAGAUCCCUCCGUCCAGCUCC 24 7685

BCLllA-7583 + CCAGCUCUCUAAGUCUCC 18 7686

BCLllA-7584 + GCCAGCUCUCUAAGUCUCC 19 7687

BCLllA-7585 + UGCCAGCUCUCUAAGUCUCC 20 7688

BCLllA-7586 + CUGCCAGCUCUCUAAGUCUCC 21 7689

BCLllA-7587 + CCUGCCAGCUCUCUAAGUCUCC 22 7690

BCLllA-7588 + CCCUGCCAGCUCUCUAAGUCUCC 23 7691

BCLllA-7589 + UCCCUGCCAGCUCUCUAAGUCUCC 24 7692

BCLllA-7590 + CGCAAACUCCCGUUCUCC 18 7693

BCLllA-7591 + GCGCAAACUCCCGUUCUCC 19 7694

BCLllA-7592 + AGCGCAAACUCCCGUUCUCC 20 7695

BCLllA-7593 + AAGCGCAAACUCCCGUUCUCC 21 7696

BCLllA-7594 + GAAGCGCAAACUCCCGU UCUCC 22 7697

BCLllA-7595 + AGAAGCGCAAACUCCCGUUCUCC 23 7698

BCLllA-7596 + GAGAAGCGCAAACUCCCGUUCUCC 24 7699

BCLllA-7597 + UCGCUGGUGCCGGGUUCC 18 7700

BCLllA-7598 + GUCGCUGGUGCCGGGUUCC 19 7701

BCLllA-6011 + AGUCGCUGGUGCCGGGUUCC 20 7702

BCLllA-7599 + AAGUCGCUGGUGCCGGGUUCC 21 7703

BCLllA-7600 + CAAGUCGCUGGUGCCGGGUUCC 22 7704

BCLllA-7601 + CCAAGUCGCUGGUGCCGGGUUCC 23 7705

BCLllA-7602 + ACCAAGUCGCUGGUGCCGGGUUCC 24 7706

BCLllA-7603 + GCCGCCUCCAGGCUCAGC 18 7707

BCLllA-7604 + CGCCGCCUCCAGGCUCAGC 19 7708

BCLllA-7605 + GCGCCGCCUCCAGGCUCAGC 20 7709

BCLllA-7606 + CGCGCCGCCUCCAGGCUCAGC 21 7710

BCLllA-7607 + GCGCGCCGCCUCCAGGCUCAGC 22 7711

BCLllA-7608 + GGCGCGCCGCCUCCAGGCUCAGC 23 7712

BCLllA-7609 + UGGCGCGCCGCCUCCAGGCUCAGC 24 7713

BCLllA-7610 + AGAAGGGGCUCAGCGAGC 18 7714

BCLllA-7611 + GAGAAGGGGCUCAGCGAGC 19 7715 BCLllA-6013 + AGAGAAGGGGCUCAGCGAGC 20 7716

BCLllA-7612 + UAGAGAAGGGGCUCAGCGAGC 21 7717

BCLllA-7613 + U UAGAGAAGGGGCUCAGCGAGC 22 7718

BCLllA-7614 + CUUAGAGAAGGGGCUCAGCGAGC 23 7719

BCLllA-7615 + GCU UAGAGAAGGGGCUCAGCGAGC 24 7720

BCLllA-7616 + CCCCCGAGGCCGACUCGC 18 7721

BCLllA-7617 + CCCCCCGAGGCCGACUCGC 19 7722

BCLllA-7618 + GCCCCCCGAGGCCGACUCGC 20 7723

BCLllA-7619 + GGCCCCCCGAGGCCGACUCGC 21 7724

BCLllA-7620 + AGGCCCCCCGAGGCCGACUCGC 22 7725

BCLllA-7621 + CAGGCCCCCCGAGGCCGACUCGC 23 7726

BCLllA-7622 + ACAGGCCCCCCGAGGCCGACUCGC 24 7727

BCLllA-7623 + AGGGAGGGGGGGCGUCGC 18 7728

BCLllA-7624 + GAGGGAGGGGGGGCGUCGC 19 7729

BCLllA-7625 + GGAGGGAGGGGGGGCGUCGC 20 7730

BCLllA-7626 + AGGAGGGAGGGGGGGCGUCGC 21 7731

BCLllA-7627 + GAGGAGGGAGGGGGGGCGUCGC 22 7732

BCLllA-7628 + AGAGGAGGGAGGGGGGGCGUCGC 23 7733

BCLllA-7629 + CAGAGGAGGGAGGGGGGGCGUCGC 24 7734

BCLllA-7630 + AGCGCCCUUCUGCCAGGC 18 7735

BCLllA-7631 + AAGCGCCCU UCUGCCAGGC 19 7736

BCLllA-6027 + AAAGCGCCCUUCUGCCAGGC 20 7737

BCLllA-7632 + GAAAGCGCCCUUCUGCCAGGC 21 7738

BCLllA-7633 + GGAAAGCGCCCU UCUGCCAGGC 22 7739

BCLllA-7634 + UGGAAAGCGCCCUUCUGCCAGGC 23 7740

BCLllA-7635 + GUGGAAAGCGCCCUUCUGCCAGGC 24 7741

BCLllA-7636 + GCAUAGGGCUGGGCCGGC 18 7742

BCLllA-7637 + UGCAUAGGGCUGGGCCGGC 19 7743

BCLllA-7638 + UUGCAUAGGGCUGGGCCGGC 20 7744

BCLllA-7639 + UUUGCAUAGGGCUGGGCCGGC 21 7745

BCLllA-7640 + CUU UGCAUAGGGCUGGGCCGGC 22 7746

BCLllA-7641 + CCUU UGCAUAGGGCUGGGCCGGC 23 7747

BCLllA-7642 + ACCUUUGCAUAGGGCUGGGCCGGC 24 7748

BCLllA-7643 + CGUGUUGGGCAUCGCGGC 18 7749

BCLllA-7644 + CCGUGUUGGGCAUCGCGGC 19 7750

BCLllA-6028 + UCCGUGUUGGGCAUCGCGGC 20 7751

BCLllA-7645 + CUCCGUGU UGGGCAUCGCGGC 21 7752

BCLllA-7646 + UCUCCGUGUUGGGCAUCGCGGC 22 7753

BCLllA-7647 + U UCUCCGUGUUGGGCAUCGCGGC 23 7754

BCLllA-7648 + GU UCUCCGUGUUGGGCAUCGCGGC 24 7755

BCLllA-7649 + AGCUGGGCCUGCCCGGGC 18 7756

BCLllA-7650 + GAGCUGGGCCUGCCCGGGC 19 7757 BCLllA-7651 + UGAGCUGGGCCUGCCCGGGC 20 7758

BCLllA-7652 + UUGAGCUGGGCCUGCCCGGGC 21 7759

BCLllA-7653 + UUUGAGCUGGGCCUGCCCGGGC 22 7760

BCLllA-7654 + UUUUGAGCUGGGCCUGCCCGGGC 23 7761

BCLllA-7655 + CUUUUGAGCUGGGCCUGCCCGGGC 24 7762

BCLllA-7656 + U UGGACUUGACCGGGGGC 18 7763

BCLllA-7657 + CUUGGACUUGACCGGGGGC 19 7764

BCLllA-6032 + ACUUGGACUUGACCGGGGGC 20 7765

BCLllA-7658 + GACUUGGACUUGACCGGGGGC 21 7766

BCLllA-7659 + UGACUUGGACUUGACCGGGGGC 22 7767

BCLllA-7660 + AUGACUUGGACUUGACCGGGGGC 23 7768

BCLllA-7661 + CAUGACUUGGACUUGACCGGGGGC 24 7769

BCLllA-7662 + CCUAGAGAAAUCCAUGGC 18 7770

BCLllA-7663 + UCCUAGAGAAAUCCAUGGC 19 7771

BCLllA-6035 + CUCCUAGAGAAAUCCAUGGC 20 7772

BCLllA-7664 + UCUCCUAGAGAAAUCCAUGGC 21 7773

BCLllA-7665 + GUCUCCUAGAGAAAUCCAUGGC 22 7774

BCLllA-7666 + AGUCUCCUAGAGAAAUCCAUGGC 23 7775

BCLllA-7667 + AAGUCUCCUAGAGAAAUCCAUGGC 24 7776

BCLllA-7668 + AUCCCAUGGAGAGGUGGC 18 7777

BCLllA-7669 + AAUCCCAUGGAGAGGUGGC 19 7778

BCLllA-6038 + GAAUCCCAUGGAGAGGUGGC 20 7779

BCLllA-7670 + UGAAUCCCAUGGAGAGGUGGC 21 7780

BCLllA-7671 + AUGAAUCCCAUGGAGAGGUGGC 22 7781

BCLllA-7672 + UAUGAAUCCCAUGGAGAGGUGGC 23 7782

BCLllA-7673 + AUAUGAAUCCCAUGGAGAGGUGGC 24 7783

BCLllA-7674 + ACUCGGGUGAUGGGUGGC 18 7784

BCLllA-7675 + CACUCGGGUGAUGGGUGGC 19 7785

BCLllA-7676 + GCACUCGGGUGAUGGGUGGC 20 7786

BCLllA-7677 + GGCACUCGGGUGAUGGGUGGC 21 7787

BCLllA-7678 + AGGCACUCGGGUGAUGGGUGGC 22 7788

BCLllA-7679 + AAGGCACUCGGGUGAUGGGUGGC 23 7789

BCLllA-7680 + AAAGGCACUCGGGUGAUGGGUGGC 24 7790

BCLllA-7681 + CUU UUGAGCUGGGCCUGC 18 7791

BCLllA-7682 + UCUUUUGAGCUGGGCCUGC 19 7792

BCLllA-7683 + CUCU UUUGAGCUGGGCCUGC 20 7793

BCLllA-7684 + CCUCUU UUGAGCUGGGCCUGC 21 7794

BCLllA-7685 + CCCUCUUU UGAGCUGGGCCUGC 22 7795

BCLllA-7686 + GCCCUCUUUUGAGCUGGGCCUGC 23 7796

BCLllA-7687 + UGCCCUCUUUUGAGCUGGGCCUGC 24 7797

BCLllA-7688 + AAGGGAUCUUUGAGCUGC 18 7798

BCLllA-7689 + GAAGGGAUCUUUGAGCUGC 19 7799 BCLllA-7690 + GGAAGGGAUCUUUGAGCUGC 20 7800

BCLllA-7691 + AGGAAGGGAUCUUUGAGCUGC 21 7801

BCLllA-7692 + AAGGAAGGGAUCUUUGAGCUGC 22 7802

BCLllA-7693 + UAAGGAAGGGAUCUUUGAGCUGC 23 7803

BCLllA-7694 + CUAAGGAAGGGAUCUU UGAGCUGC 24 7804

BCLllA-7695 + GCCUCGCUGAAGUGCUGC 18 7805

BCLllA-7696 + GGCCUCGCUGAAGUGCUGC 19 7806

BCLllA-7697 + AGGCCUCGCUGAAGUGCUGC 20 7807

BCLllA-7698 + AAGGCCUCGCUGAAGUGCUGC 21 7808

BCLllA-7699 + GAAGGCCUCGCUGAAGUGCUGC 22 7809

BCLllA-7700 + GGAAGGCCUCGCUGAAGUGCUGC 23 7810

BCLllA-7701 + UGGAAGGCCUCGCUGAAGUGCUGC 24 7811

BCLllA-7702 + GUGUUCUGUGCGUGUUGC 18 7812

BCLllA-7703 + AGUGUUCUGUGCGUGU UGC 19 7813

BCLllA-7704 + GAGUGUUCUGUGCGUGUUGC 20 7814

BCLllA-7705 + UGAGUGUUCUGUGCGUGUUGC 21 7815

BCLllA-7706 + AUGAGUGUUCUGUGCGUGUUGC 22 7816

BCLllA-7707 + CAUGAGUGUUCUGUGCGUGUUGC 23 7817

BCLllA-7708 + CCAUGAGUGUUCUGUGCGUGUUGC 24 7818

BCLllA-7709 + CGAAAACUGCCACACAUC 18 7819

BCLllA-7710 + CCGAAAACUGCCACACAUC 19 7820

BCLllA-7711 + UCCGAAAACUGCCACACAUC 20 7821

BCLllA-7712 + AUCCGAAAACUGCCACACAUC 21 7822

BCLllA-7713 + CAUCCGAAAACUGCCACACAUC 22 7823

BCLllA-7714 + CCAUCCGAAAACUGCCACACAUC 23 7824

BCLllA-7715 + UCCAUCCGAAAACUGCCACACAUC 24 7825

BCLllA-7716 + U UGGGGUCGUUCUCGCUC 18 7826

BCLllA-7717 + GUUGGGGUCGUUCUCGCUC 19 7827

BCLllA-7718 + GGU UGGGGUCGUUCUCGCUC 20 7828

BCLllA-7719 + AGGUUGGGGUCGUUCUCGCUC 21 7829

BCLllA-7720 + CAGGUUGGGGUCGUUCUCGCUC 22 7830

BCLllA-7721 + UCAGGUUGGGGUCGUUCUCGCUC 23 7831

BCLllA-7722 + AUCAGGUUGGGGUCGUUCUCGCUC 24 7832

BCLllA-7723 + CUCAGAACUUAAGGGCUC 18 7833

BCLllA-7724 + UCUCAGAACUUAAGGGCUC 19 7834

BCLllA-7725 + U UCUCAGAACUUAAGGGCUC 20 7835

BCLllA-7726 + U UUCUCAGAACUUAAGGGCUC 21 7836

BCLllA-7727 + U UUUCUCAGAACUUAAGGGCUC 22 7837

BCLllA-7728 + AUUUUCUCAGAACUUAAGGGCUC 23 7838

BCLllA-7729 + AAUUUUCUCAGAACUUAAGGGCUC 24 7839

BCLllA-7730 + GACAUUCUGCACCUAGUC 18 7840

BCLllA-7731 + GGACAUUCUGCACCUAGUC 19 7841 BCLllA-7732 + AGGACAUUCUGCACCUAGUC 20 7842

BCLllA-7733 + AAGGACAUUCUGCACCUAGUC 21 7843

BCLllA-7734 + GAAGGACAUUCUGCACCUAGUC 22 7844

BCLllA-7735 + GGAAGGACAUUCUGCACCUAGUC 23 7845

BCLllA-7736 + GGGAAGGACAUUCUGCACCUAGUC 24 7846

BCLllA-7737 + UCGUCGGACUUGACCGUC 18 7847

BCLllA-7738 + GUCGUCGGACUUGACCGUC 19 7848

BCLllA-7739 + CGUCGUCGGACUUGACCGUC 20 7849

BCLllA-7740 + CCGUCGUCGGACUUGACCGUC 21 7850

BCLllA-7741 + ACCGUCGUCGGACUUGACCGUC 22 7851

BCLllA-7742 + GACCGUCGUCGGACUUGACCGUC 23 7852

BCLllA-7743 + AGACCGUCGUCGGACUUGACCGUC 24 7853

BCLllA-7744 + AUACCAACCCGCGGGGUC 18 7854

BCLllA-7745 + GAUACCAACCCGCGGGGUC 19 7855

BCLllA-6052 + GGAUACCAACCCGCGGGGUC 20 7856

BCLllA-7746 + GGGAUACCAACCCGCGGGGUC 21 7857

BCLllA-7747 + AGGGAUACCAACCCGCGGGGUC 22 7858

BCLllA-7748 + AAGGGAUACCAACCCGCGGGGUC 23 7859

BCLllA-7749 + GAAGGGAUACCAACCCGCGGGGUC 24 7860

BCLllA-7750 + GGCAGGUCGAACUCCUUC 18 7861

BCLllA-7751 + GGGCAGGUCGAACUCCU UC 19 7862

BCLllA-7752 + GGGGCAGGUCGAACUCCUUC 20 7863

BCLllA-7753 + GGGGGCAGGUCGAACUCCUUC 21 7864

BCLllA-7754 + CGGGGGCAGGUCGAACUCCUUC 22 7865

BCLllA-7755 + CCGGGGGCAGGUCGAACUCCUUC 23 7866

BCLllA-7756 + GCCGGGGGCAGGUCGAACUCCUUC 24 7867

BCLllA-7757 + GUCGCUGGUGCCGGGU UC 18 7868

BCLllA-7758 + AGUCGCUGGUGCCGGGUUC 19 7869

BCLllA-6058 + AAGUCGCUGGUGCCGGGUUC 20 7870

BCLllA-7759 + CAAGUCGCUGGUGCCGGGUUC 21 7871

BCLllA-7760 + CCAAGUCGCUGGUGCCGGGUUC 22 7872

BCLllA-7761 + ACCAAGUCGCUGGUGCCGGGUUC 23 7873

BCLllA-7762 + CACCAAGUCGCUGGUGCCGGGUUC 24 7874

BCLllA-7763 + CGGUGGUGGACUAAACAG 18 7875

BCLllA-7764 + UCGGUGGUGGACUAAACAG 19 7876

BCLllA-6063 + CUCGGUGGUGGACUAAACAG 20 7877

BCLllA-7765 + UCUCGGUGGUGGACUAAACAG 21 7878

BCLllA-7766 + GUCUCGGUGGUGGACUAAACAG 22 7879

BCLllA-7767 + UGUCUCGGUGGUGGACUAAACAG 23 7880

BCLllA-7768 + AUGUCUCGGUGGUGGACUAAACAG 24 7881

BCLllA-7769 + GAAAGAGGUUGGAGACAG 18 7882

BCLllA-7770 + AG AAAG AGG U UGG AG ACAG 19 7883 BCLllA-6064 + UAGAAAGAGGUUGGAGACAG 20 7884

BCLllA-7771 + CU AG AAAG AGG U UGG AG ACAG 21 7885

BCLllA-7772 + CCUAGAAAGAGGUUGGAGACAG 22 7886

BCLllA-7773 + ACCU AGAAAG AGG UUGGAG ACAG 23 7887

BCLllA-7774 + AACCUAGAAAGAGGUUGGAGACAG 24 7888

BCLllA-7775 + AGGAGGGGCGGAUUGCAG 18 7889

BCLllA-7776 + GAGGAGGGGCGGAUUGCAG 19 7890

BCLllA-6069 + GGAGGAGGGGCGGAUUGCAG 20 7891

BCLllA-7777 + GGGAGGAGGGGCGGAU UGCAG 21 7892

BCLllA-7778 + AGGGAGGAGGGGCGGAUUGCAG 22 7893

BCLllA-7779 + GAGGGAGGAGGGGCGGAUUGCAG 23 7894

BCLllA-7780 + GGAGGGAGGAGGGGCGGAUUGCAG 24 7895

BCLllA-7781 + AAG AGG U UGG AG ACAG AG 18 7896

BCLllA-7782 + AAAGAGGUUGGAGACAGAG 19 7897

BCLllA-7783 + GAAAGAGGUUGGAGACAGAG 20 7898

BCLllA-7784 + AG AAAG AGG U UGG AG ACAG AG 21 7899

BCLllA-7785 + UAGAAAGAGGUUGGAGACAGAG 22 7900

BCLllA-7786 + CU AG AAAG AGG U UGG AG ACAG AG 23 7901

BCLllA-7787 + CCU AG AAAG AGG U UGG AG ACAG AG 24 7902

BCLllA-7788 + GAGGGGCGGAUUGCAGAG 18 7903

BCLllA-7789 + GGAGGGGCGGAUUGCAGAG 19 7904

BCLllA-7790 + AGGAGGGGCGGAUUGCAGAG 20 7905

BCLllA-7791 + GAGGAGGGGCGGAUUGCAGAG 21 7906

BCLllA-7792 + GGAGGAGGGGCGGAUUGCAGAG 22 7907

BCLllA-7793 + GGGAGGAGGGGCGGAU UGCAGAG 23 7908

BCLllA-7794 + AGGGAGGAGGGGCGGAUUGCAGAG 24 7909

BCLllA-7795 + AGCUUGAUGCGCUUAGAG 18 7910

BCLllA-7796 + GAGCUUGAUGCGCUUAGAG 19 7911

BCLllA-7797 + CGAGCUUGAUGCGCUUAGAG 20 7912

BCLllA-7798 + UCGAGCUUGAUGCGCU UAGAG 21 7913

BCLllA-7799 + CUCGAGCU UGAUGCGCUUAGAG 22 7914

BCLllA-7800 + UCUCGAGCUUGAUGCGCUUAGAG 23 7915

BCLllA-7801 + U UCUCGAGCUUGAUGCGCUUAGAG 24 7916

BCLllA-7802 + GAGAAGGGGCUCAGCGAG 18 7917

BCLllA-7803 + AGAGAAGGGGCUCAGCGAG 19 7918

BCLllA-7804 + UAGAGAAGGGGCUCAGCGAG 20 7919

BCLllA-7805 + UUAGAGAAGGGGCUCAGCGAG 21 7920

BCLllA-7806 + CUU AGAGAAGGGGCUCAGCGAG 22 7921

BCLllA-7807 + GCUUAGAGAAGGGGCUCAGCGAG 23 7922

BCLllA-7808 + CGCUUAGAGAAGGGGCUCAGCGAG 24 7923

BCLllA-7809 + GGAUUGCAGAGGAGGGAG 18 7924

BCLllA-7810 + CGGAUUGCAGAGGAGGGAG 19 7925 BCLllA-6075 + GCGGAUUGCAGAGGAGGGAG 20 7926

BCLllA-7811 + GGCGGAUUGCAGAGGAGGGAG 21 7927

BCLllA-7812 + GGGCGGAUUGCAGAGGAGGGAG 22 7928

BCLllA-7813 + GGGGCGGAUUGCAGAGGAGGGAG 23 7929

BCLllA-7814 + AGGGGCGGAUUGCAGAGGAGGGAG 24 7930

BCLllA-7815 + CCGGGGGCUGGGAGGGAG 18 7931

BCLllA-7816 + ACCGGGGGCUGGGAGGGAG 19 7932

BCLllA-7817 + GACCGGGGGCUGGGAGGGAG 20 7933

BCLllA-7818 + UGACCGGGGGCUGGGAGGGAG 21 7934

BCLllA-7819 + U UGACCGGGGGCUGGGAGGGAG 22 7935

BCLllA-7820 + CUUGACCGGGGGCUGGGAGGGAG 23 7936

BCLllA-7821 + ACUUGACCGGGGGCUGGGAGGGAG 24 7937

BCLllA-7822 + CUGAAGUGCUGCAUGGAG 18 7938

BCLllA-7823 + GCUGAAGUGCUGCAUGGAG 19 7939

BCLllA-7824 + CGCUGAAGUGCUGCAUGGAG 20 7940

BCLllA-7825 + UCGCUGAAGUGCUGCAUGGAG 21 7941

BCLllA-7826 + CUCGCUGAAGUGCUGCAUGGAG 22 7942

BCLllA-7827 + CCUCGCUGAAGUGCUGCAUGGAG 23 7943

BCLllA-7828 + GCCUCGCUGAAGUGCUGCAUGGAG 24 7944

BCLllA-7829 + CGUCUGCCCUCUUUUGAG 18 7945

BCLllA-7830 + GCGUCUGCCCUCUUUUGAG 19 7946

BCLllA-7831 + UGCGUCUGCCCUCUUUUGAG 20 7947

BCLllA-7832 + CUGCGUCUGCCCUCU UUUGAG 21 7948

BCLllA-7833 + GCUGCGUCUGCCCUCU U UUGAG 22 7949

BCLllA-7834 + CGCUGCGUCUGCCCUCU UUUGAG 23 7950

BCLllA-7835 + UCGCUGCGUCUGCCCUCUUUUGAG 24 7951

BCLllA-7836 + CCGAGGAGUGCUCCGACG 18 7952

BCLllA-7837 + UCCGAGGAGUGCUCCGACG 19 7953

BCLllA-6080 + CUCCGAGGAGUGCUCCGACG 20 7954

BCLllA-7838 + UCUCCGAGGAGUGCUCCGACG 21 7955

BCLllA-7839 + U UCUCCGAGGAGUGCUCCGACG 22 7956

BCLllA-7840 + GU UCUCCGAGGAGUGCUCCGACG 23 7957

BCLllA-7841 + CGU UCUCCGAGGAGUGCUCCGACG 24 7958

BCLllA-7842 + ACCAUGCCCUGCAUGACG 18 7959

BCLllA-7843 + CACCAUGCCCUGCAUGACG 19 7960

BCLllA-7844 + GCACCAUGCCCUGCAUGACG 20 7961

BCLllA-7845 + AGCACCAUGCCCUGCAUGACG 21 7962

BCLllA-7846 + GAGCACCAUGCCCUGCAUGACG 22 7963

BCLllA-7847 + UGAGCACCAUGCCCUGCAUGACG 23 7964

BCLllA-7848 + CUGAGCACCAUGCCCUGCAUGACG 24 7965

BCLllA-7849 + CCGAGGCCGACUCGCCCG 18 7966

BCLllA-7850 + CCCGAGGCCGACUCGCCCG 19 7967 BCLllA-6088 + CCCCGAGGCCGACUCGCCCG 20 7968

BCLllA-7851 + CCCCCGAGGCCGACUCGCCCG 21 7969

BCLllA-7852 + CCCCCCGAGGCCGACUCGCCCG 22 7970

BCLllA-7853 + GCCCCCCGAGGCCGACUCGCCCG 23 7971

BCLllA-7854 + GGCCCCCCGAGGCCGACUCGCCCG 24 7972

BCLllA-7855 + CUGGAGGCCGCGUAGCCG 18 7973

BCLllA-7856 + CCUGGAGGCCGCGUAGCCG 19 7974

BCLllA-7857 + GCCUGGAGGCCGCGUAGCCG 20 7975

BCLllA-7858 + UGCCUGGAGGCCGCGUAGCCG 21 7976

BCLllA-7859 + CUGCCUGGAGGCCGCGUAGCCG 22 7977

BCLllA-7860 + GCUGCCUGGAGGCCGCGUAGCCG 23 7978

BCLllA-7861 + AGCUGCCUGGAGGCCGCGUAGCCG 24 7979

BCLllA-7862 + AAUUUGAACGUCUUGCCG 18 7980

BCLllA-7863 + AAAUUUGAACGUCUUGCCG 19 7981

BCLllA-7864 + GAAAUUUGAACGUCUUGCCG 20 7982

BCLllA-7865 + UGAAAUUUGAACGUCUUGCCG 21 7983

BCLllA-7866 + CUGAAAUUUGAACGUCUUGCCG 22 7984

BCLllA-7867 + UCUGAAAUUUGAACGUCUUGCCG 23 7985

BCLllA-7868 + CUCUGAAAUUUGAACGUCUUGCCG 24 7986

BCLllA-7869 + UCUCCGAGGAGUGCUCCG 18 7987

BCLllA-7870 + UUCUCCGAGGAGUGCUCCG 19 7988

BCLllA-7871 + GUUCUCCGAGGAGUGCUCCG 20 7989

BCLllA-7872 + CGUUCUCCGAGGAGUGCUCCG 21 7990

BCLllA-7873 + CCGUUCUCCGAGGAGUGCUCCG 22 7991

BCLllA-7874 + CCCGUUCUCCGAGGAGUGCUCCG 23 7992

BCLllA-7875 + UCCCGU UCUCCGAGGAGUGCUCCG 24 7993

BCLllA-7876 + CGCUGGUGCCGGGUUCCG 18 7994

BCLllA-7877 + UCGCUGGUGCCGGGUUCCG 19 7995

BCLllA-6096 + GUCGCUGGUGCCGGGUUCCG 20 7996

BCLllA-7878 + AGUCGCUGGUGCCGGGUUCCG 21 7997

BCLllA-7879 + AAGUCGCUGGUGCCGGGUUCCG 22 7998

BCLllA-7880 + CAAGUCGCUGGUGCCGGGUUCCG 23 7999

BCLllA-7881 + CCAAGUCGCUGGUGCCGGGUUCCG 24 8000

BCLllA-7882 + GCCGGCCUGGGGACAGCG 18 8001

BCLllA-7883 + GGCCGGCCUGGGGACAGCG 19 8002

BCLllA-7884 + GGGCCGGCCUGGGGACAGCG 20 8003

BCLllA-7885 + UGGGCCGGCCUGGGGACAGCG 21 8004

BCLllA-7886 + CUGGGCCGGCCUGGGGACAGCG 22 8005

BCLllA-7887 + GCUGGGCCGGCCUGGGGACAGCG 23 8006

BCLllA-7888 + GGCUGGGCCGGCCUGGGGACAGCG 24 8007

BCLllA-7889 + GGU UCCGGGGAGCUGGCG 18 8008

BCLllA-7890 + GGGUUCCGGGGAGCUGGCG 19 8009 BCLllA-7891 + CGGGUUCCGGGGAGCUGGCG 20 8010

BCLllA-7892 + CCGGGUUCCGGGGAGCUGGCG 21 8011

BCLllA-7893 + GCCGGGUUCCGGGGAGCUGGCG 22 8012

BCLllA-7894 + UGCCGGGU UCCGGGGAGCUGGCG 23 8013

BCLllA-7895 + GUGCCGGGUUCCGGGGAGCUGGCG 24 8014

BCLllA-7896 + CCCCAGGCGCUCUAUGCG 18 8015

BCLllA-7897 + CCCCCAGGCGCUCUAUGCG 19 8016

BCLllA-7898 + GCCCCCAGGCGCUCUAUGCG 20 8017

BCLllA-7899 + CGCCCCCAGGCGCUCUAUGCG 21 8018

BCLllA-7900 + CCGCCCCCAGGCGCUCUAUGCG 22 8019

BCLllA-7901 + UCCGCCCCCAGGCGCUCUAUGCG 23 8020

BCLllA-7902 + U UCCGCCCCCAGGCGCUCUAUGCG 24 8021

BCLllA-7903 + ACCUGGUGGAAGGCCUCG 18 8022

BCLllA-7904 + GACCUGGUGGAAGGCCUCG 19 8023

BCLllA-7905 + GGACCUGGUGGAAGGCCUCG 20 8024

BCLllA-7906 + AGGACCUGGUGGAAGGCCUCG 21 8025

BCLllA-7907 + CAGGACCUGGUGGAAGGCCUCG 22 8026

BCLllA-7908 + CCAGGACCUGGUGGAAGGCCUCG 23 8027

BCLllA-7909 + CCCAGGACCUGGUGGAAGGCCUCG 24 8028

BCLllA-7910 + GCGGUGGAGAGACCGUCG 18 8029

BCLllA-7911 + GGCGGUGGAGAGACCGUCG 19 8030

BCLllA-7912 + UGGCGGUGGAGAGACCGUCG 20 8031

BCLllA-7913 + CUGGCGGUGGAGAGACCGUCG 21 8032

BCLllA-7914 + GCUGGCGGUGGAGAGACCGUCG 22 8033

BCLllA-7915 + AGCUGGCGGUGGAGAGACCGUCG 23 8034

BCLllA-7916 + GAGCUGGCGGUGGAGAGACCGUCG 24 8035

BCLllA-7917 + GAGUCUCCGAAGCUAAGG 18 8036

BCLllA-7918 + GGAGUCUCCGAAGCUAAGG 19 8037

BCLllA-7919 + UGGAGUCUCCGAAGCUAAGG 20 8038

BCLllA-7920 + CUGGAGUCUCCGAAGCUAAGG 21 8039

BCLllA-7921 + UCUGGAGUCUCCGAAGCUAAGG 22 8040

BCLllA-7922 + GUCUGGAGUCUCCGAAGCUAAGG 23 8041

BCLllA-7923 + UGUCUGGAGUCUCCGAAGCUAAGG 24 8042

BCLllA-7924 + GGUGGUGGACUAAACAGG 18 8043

BCLllA-7925 + CGGUGGUGGACUAAACAGG 19 8044

BCLllA-6111 + UCGGUGGUGGACUAAACAGG 20 8045

BCLllA-7926 + CUCGGUGGUGGACUAAACAGG 21 8046

BCLllA-7927 + UCUCGGUGGUGGACUAAACAGG 22 8047

BCLllA-7928 + GUCUCGGUGGUGGACUAAACAGG 23 8048

BCLllA-7929 + UGUCUCGGUGGUGGACUAAACAGG 24 8049

BCLllA-7930 + AGGGGGGGCGUCGCCAGG 18 8050

BCLllA-7931 + GAGGGGGGGCGUCGCCAGG 19 8051 BCLllA-7932 + GGAGGGGGGGCGUCGCCAGG 20 8052

BCLllA-7933 + GGGAGGGGGGGCGUCGCCAGG 21 8053

BCLllA-7934 + AGGGAGGGGGGGCGUCGCCAGG 22 8054

BCLllA-7935 + GAGGGAGGGGGGGCGUCGCCAGG 23 8055

BCLllA-7936 + GGAGGGAGGGGGGGCGUCGCCAGG 24 8056

BCLllA-7937 + AAGCGCCCU UCUGCCAGG 18 8057

BCLllA-7938 + AAAGCGCCCUUCUGCCAGG 19 8058

BCLllA-7939 + GAAAGCGCCCUUCUGCCAGG 20 8059

BCLllA-7940 + GGAAAGCGCCCUUCUGCCAGG 21 8060

BCLllA-7941 + UGGAAAGCGCCCUUCUGCCAGG 22 8061

BCLllA-7942 + GUGGAAAGCGCCCUUCUGCCAGG 23 8062

BCLllA-7943 + GGUGGAAAGCGCCCUUCUGCCAGG 24 8063

BCLllA-7944 + AUCGCGGCCGGGGGCAGG 18 8064

BCLllA-7945 + CAUCGCGGCCGGGGGCAGG 19 8065

BCLllA-7946 + GCAUCGCGGCCGGGGGCAGG 20 8066

BCLllA-7947 + GGCAUCGCGGCCGGGGGCAGG 21 8067

BCLllA-7948 + GGGCAUCGCGGCCGGGGGCAGG 22 8068

BCLllA-7949 + UGGGCAUCGCGGCCGGGGGCAGG 23 8069

BCLllA-7950 + U UGGGCAUCGCGGCCGGGGGCAGG 24 8070

BCLllA-7951 + CCGUUCUCCGGGAUCAGG 18 8071

BCLllA-7952 + CCCGUUCUCCGGGAUCAGG 19 8072

BCLllA-7953 + CCCCGUUCUCCGGGAUCAGG 20 8073

BCLllA-7954 + UCCCCGUUCUCCGGGAUCAGG 21 8074

BCLllA-7955 + GUCCCCGUUCUCCGGGAUCAGG 22 8075

BCLllA-7956 + CGUCCCCGUUCUCCGGGAUCAGG 23 8076

BCLllA-7957 + UCGUCCCCGUUCUCCGGGAUCAGG 24 8077

BCLllA-7958 + GAAGAACCUAGAAAGAGG 18 8078

BCLllA-7959 + UGAAGAACCUAGAAAGAGG 19 8079

BCLllA-7960 + GUGAAGAACCUAGAAAGAGG 20 8080

BCLllA-7961 + UGUGAAGAACCUAGAAAGAGG 21 8081

BCLllA-7962 + GUG UGAAGAACCUAGAAAGAGG 22 8082

BCLllA-7963 + UGUGUGAAGAACCUAGAAAGAGG 23 8083

BCLllA-7964 + GUGUGUGAAGAACCUAGAAAGAGG 24 8084

BCLllA-7965 + AGAGGUUGGAGACAGAGG 18 8085

BCLllA-7966 + AAGAGGUUGGAGACAGAGG 19 8086

BCLllA-6113 + AAAGAGGUUGGAGACAGAGG 20 8087

BCLllA-7967 + GAAAGAGGUUGGAGACAGAGG 21 8088

BCLllA-7968 + AGAAAGAGGUUGGAGACAGAGG 22 8089

BCLllA-7969 + UAGAAAGAGGUUGGAGACAGAGG 23 8090

BCLllA-7970 + CU AG AAAG AGG U UGG AG ACAG AGG 24 8091

BCLllA-7971 + AGGGGCGGAUUGCAGAGG 18 8092

BCLllA-7972 + GAGGGGCGGAUUGCAGAGG 19 8093 BCLllA-6114 + GGAGGGGCGGAUUGCAGAGG 20 8094

BCLllA-7973 + AGGAGGGGCGGAUUGCAGAGG 21 8095

BCLllA-7974 + GAGGAGGGGCGGAUUGCAGAGG 22 8096

BCLllA-7975 + GGAGGAGGGGCGGAUUGCAGAGG 23 8097

BCLllA-7976 + GGGAGGAGGGGCGGAU UGCAGAGG 24 8098

BCLllA-7977 + GGCGGAUUGCAGAGGAGG 18 8099

BCLllA-7978 + GGGCGGAUUGCAGAGGAGG 19 8100

BCLllA-7979 + GGGGCGGAUUGCAGAGGAGG 20 8101

BCLllA-7980 + AGGGGCGGAUUGCAGAGGAGG 21 8102

BCLllA-7981 + GAGGGGCGGAUUGCAGAGGAGG 22 8103

BCLllA-7982 + GGAGGGGCGGAUUGCAGAGGAGG 23 8104

BCLllA-7983 + AGGAGGGGCGGAUUGCAGAGGAGG 24 8105

BCLllA-7984 + GAUUGCAGAGGAGGGAGG 18 8106

BCLllA-7985 + GGAUUGCAGAGGAGGGAGG 19 8107

BCLllA-6118 + CGGAUUGCAGAGGAGGGAGG 20 8108

BCLllA-7986 + GCGGAUUGCAGAGGAGGGAGG 21 8109

BCLllA-7987 + GGCGGAUUGCAGAGGAGGGAGG 22 8110

BCLllA-7988 + GGGCGGAUUGCAGAGGAGGGAGG 23 8111

BCLllA-7989 + GGGGCGGAUUGCAGAGGAGGGAGG 24 8112

BCLllA-7990 + CGGGGGCUGGGAGGGAGG 18 8113

BCLllA-7991 + CCGGGGGCUGGGAGGGAGG 19 8114

BCLllA-6119 + ACCGGGGGCUGGGAGGGAGG 20 8115

BCLllA-7992 + GACCGGGGGCUGGGAGGGAGG 21 8116

BCLllA-7993 + UGACCGGGGGCUGGGAGGGAGG 22 8117

BCLllA-7994 + U UGACCGGGGGCUGGGAGGGAGG 23 8118

BCLllA-7995 + CUUGACCGGGGGCUGGGAGGGAGG 24 8119

BCLllA-7996 + UGACCGGGGGCUGGGAGG 18 8120

BCLllA-7997 + U UGACCGGGGGCUGGGAGG 19 8121

BCLllA-7998 + CUUGACCGGGGGCUGGGAGG 20 8122

BCLllA-7999 + ACUUGACCGGGGGCUGGGAGG 21 8123

BCLllA-8000 + GACUUGACCGGGGGCUGGGAGG 22 8124

BCLllA-8001 + GGACUUGACCGGGGGCUGGGAGG 23 8125

BCLllA-8002 + UGGACUUGACCGGGGGCUGGGAGG 24 8126

BCLllA-8003 + CCGUGU UGGGCAUCGCGG 18 8127

BCLllA-8004 + UCCGUGUUGGGCAUCGCGG 19 8128

BCLllA-8005 + CUCCGUGUUGGGCAUCGCGG 20 8129

BCLllA-8006 + UCUCCGUGUUGGGCAUCGCGG 21 8130

BCLllA-8007 + UUCUCCGUGUUGGGCAUCGCGG 22 8131

BCLllA-8008 + GU UCUCCGUGUUGGGCAUCGCGG 23 8132

BCLllA-8009 + CGUUCUCCGUGU UGGGCAUCGCGG 24 8133

BCLllA-8010 + GUUCCGGGGAGCUGGCGG 18 8134

BCLllA-8011 + GGU UCCGGGGAGCUGGCGG 19 8135 BCLllA-6125 + GGGUUCCGGGGAGCUGGCGG 20 8136

BCLllA-8012 + CGGGU UCCGGGGAGCUGGCGG 21 8137

BCLllA-8013 + CCGGGUUCCGGGGAGCUGGCGG 22 8138

BCLllA-8014 + GCCGGGUUCCGGGGAGCUGGCGG 23 8139

BCLllA-8015 + UGCCGGGUUCCGGGGAGCUGGCGG 24 8140

BCLllA-8016 + CCCAGGCGCUCUAUGCGG 18 8141

BCLllA-8017 + CCCCAGGCGCUCUAUGCGG 19 8142

BCLllA-6126 + CCCCCAGGCGCUCUAUGCGG 20 8143

BCLllA-8018 + GCCCCCAGGCGCUCUAUGCGG 21 8144

BCLllA-8019 + CGCCCCCAGGCGCUCUAUGCGG 22 8145

BCLllA-8020 + CCGCCCCCAGGCGCUCUAUGCGG 23 8146

BCLllA-8021 + UCCGCCCCCAGGCGCUCUAUGCGG 24 8147

BCLllA-8022 + GUGGUGGACUAAACAGGG 18 8148

BCLllA-8023 + GGUGGUGGACUAAACAGGG 19 8149

BCLllA-6131 + CGGUGGUGGACUAAACAGGG 20 8150

BCLllA-8024 + UCGGUGGUGGACUAAACAGGG 21 8151

BCLllA-8025 + CUCGGUGGUGGACUAAACAGGG 22 8152

BCLllA-8026 + UCUCGGUGGUGGACUAAACAGGG 23 8153

BCLllA-8027 + GUCUCGGUGGUGGACUAAACAGGG 24 8154

BCLllA-8028 + GCGGAUUGCAGAGGAGGG 18 8155

BCLllA-8029 + GGCGGAUUGCAGAGGAGGG 19 8156

BCLllA-6133 + GGGCGGAUUGCAGAGGAGGG 20 8157

BCLllA-8030 + GGGGCGGAUUGCAGAGGAGGG 21 8158

BCLllA-8031 + AGGGGCGGAUUGCAGAGGAGGG 22 8159

BCLllA-8032 + GAGGGGCGGAUUGCAGAGGAGGG 23 8160

BCLllA-8033 + GGAGGGGCGGAUUGCAGAGGAGGG 24 8161

BCLllA-8034 + GACCGGGGGCUGGGAGGG 18 8162

BCLllA-8035 + UGACCGGGGGCUGGGAGGG 19 8163

BCLllA-6135 + U UGACCGGGGGCUGGGAGGG 20 8164

BCLllA-8036 + CUUGACCGGGGGCUGGGAGGG 21 8165

BCLllA-8037 + ACU UGACCGGGGGCUGGGAGGG 22 8166

BCLllA-8038 + GACUUGACCGGGGGCUGGGAGGG 23 8167

BCLllA-8039 + GGACUUGACCGGGGGCUGGGAGGG 24 8168

BCLllA-8040 + AGUAACCUUUGCAUAGGG 18 8169

BCLllA-8041 + CAGUAACCUUUGCAUAGGG 19 8170

BCLllA-8042 + GCAGUAACCUUUGCAUAGGG 20 8171

BCLllA-8043 + UGCAGUAACCUU UGCAUAGGG 21 8172

BCLllA-8044 + U UGCAGUAACCU UUGCAUAGGG 22 8173

BCLllA-8045 + GUUGCAGUAACCUUUGCAUAGGG 23 8174

BCLllA-8046 + GGU UGCAGUAACCUUUGCAUAGGG 24 8175

BCLllA-8047 + GCCCUGCAUGACGUCGGG 18 8176

BCLllA-8048 + UGCCCUGCAUGACGUCGGG 19 8177 BCLllA-8049 + AUGCCCUGCAUGACGUCGGG 20 8178

BCLllA-8050 + CAUGCCCUGCAUGACGUCGGG 21 8179

BCLllA-8051 + CCAUGCCCUGCAUGACGUCGGG 22 8180

BCLllA-8052 + ACCAUGCCCUGCAUGACGUCGGG 23 8181

BCLllA-8053 + CACCAUGCCCUGCAUGACGUCGGG 24 8182

BCLllA-8054 + CUUGGACUUGACCGGGGG 18 8183

BCLllA-8055 + ACU UGGACUUGACCGGGGG 19 8184

BCLllA-8056 + GACUUGGACUUGACCGGGGG 20 8185

BCLllA-8057 + UGACUUGGACUUGACCGGGGG 21 8186

BCLllA-8058 + AUGACUUGGACUUGACCGGGGG 22 8187

BCLllA-8059 + CAUGACUUGGACUUGACCGGGGG 23 8188

BCLllA-8060 + GCAUGACUUGGACUUGACCGGGGG 24 8189

BCLllA-8061 + ACUUGACCGGGGGCUGGG 18 8190

BCLllA-8062 + GACUUGACCGGGGGCUGGG 19 8191

BCLllA-6146 + GGACUUGACCGGGGGCUGGG 20 8192

BCLllA-8063 + UGGACUUGACCGGGGGCUGGG 21 8193

BCLllA-8064 + UUGGACUUGACCGGGGGCUGGG 22 8194

BCLllA-8065 + CUUGGACUUGACCGGGGGCUGGG 23 8195

BCLllA-8066 + ACU UGGACUUGACCGGGGGCUGGG 24 8196

BCLllA-8067 + CAUGGAGAGGUGGCUGGG 18 8197

BCLllA-8068 + CCAUGGAGAGGUGGCUGGG 19 8198

BCLllA-8069 + CCCAUGGAGAGGUGGCUGGG 20 8199

BCLllA-8070 + UCCCAUGGAGAGGUGGCUGGG 21 8200

BCLllA-8071 + AUCCCAUGGAGAGGUGGCUGGG 22 8201

BCLllA-8072 + AAUCCCAUGGAGAGGUGGCUGGG 23 8202

BCLllA-8073 + GAAUCCCAUGGAGAGGUGGCUGGG 24 8203

BCLllA-8074 + AAACAGGGGGGGAGUGGG 18 8204

BCLllA-8075 + UAAACAGGGGGGGAGUGGG 19 8205

BCLllA-6147 + CUAAACAGGGGGGGAGUGGG 20 8206

BCLllA-8076 + ACU AAACAGGGGGGGAGUGGG 21 8207

BCLllA-8077 + GACUAAACAGGGGGGGAGUGGG 22 8208

BCLllA-8078 + GGACUAAACAGGGGGGGAGUGGG 23 8209

BCLllA-8079 + UGGACUAAACAGGGGGGGAGUGGG 24 8210

BCLllA-8080 + UCCUAGAGAAAUCCAUGG 18 8211

BCLllA-8081 + CUCCUAGAGAAAUCCAUGG 19 8212

BCLllA-6149 + UCUCCUAGAGAAAUCCAUGG 20 8213

BCLllA-8082 + GUCUCCUAGAGAAAUCCAUGG 21 8214

BCLllA-8083 + AGUCUCCUAGAGAAAUCCAUGG 22 8215

BCLllA-8084 + AAGUCUCCUAGAGAAAUCCAUGG 23 8216

BCLllA-8085 + UAAGUCUCCUAGAGAAAUCCAUGG 24 8217

BCLllA-8086 + U UCUCGCCCAGGACCUGG 18 8218

BCLllA-8087 + CUUCUCGCCCAGGACCUGG 19 8219 BCLllA-6152 + GCU UCUCGCCCAGGACCUGG 20 8220

BCLllA-8088 + UGCUUCUCGCCCAGGACCUGG 21 8221

BCLllA-8089 + AUGCUUCUCGCCCAGGACCUGG 22 8222

BCLllA-8090 + UAUGCUUCUCGCCCAGGACCUGG 23 8223

BCLllA-8091 + UUAUGCUUCUCGCCCAGGACCUGG 24 8224

BCLllA-8092 + GGGCGGCUUGCUACCUGG 18 8225

BCLllA-8093 + AGGGCGGCUUGCUACCUGG 19 8226

BCLllA-8094 + AAGGGCGGCUUGCUACCUGG 20 8227

BCLllA-8095 + GAAGGGCGGCUUGCUACCUGG 21 8228

BCLllA-8096 + GGAAGGGCGGCUUGCUACCUGG 22 8229

BCLllA-8097 + AGGAAGGGCGGCUUGCUACCUGG 23 8230

BCLllA-8098 + CAGGAAGGGCGGCU UGCUACCUGG 24 8231

BCLllA-8099 + GACUUGACCGGGGGCUGG 18 8232

BCLllA-8100 + GGACUUGACCGGGGGCUGG 19 8233

BCLllA-8101 + UGGACUUGACCGGGGGCUGG 20 8234

BCLllA-8102 + U UGGACUUGACCGGGGGCUGG 21 8235

BCLllA-8103 + CUUGGACUUGACCGGGGGCUGG 22 8236

BCLllA-8104 + ACU UGGACUUGACCGGGGGCUGG 23 8237

BCLllA-8105 + GACUUGGACUUGACCGGGGGCUGG 24 8238

BCLllA-8106 + UAAACAGGGGGGGAGUGG 18 8239

BCLllA-8107 + CUAAACAGGGGGGGAGUGG 19 8240

BCLllA-8108 + ACUAAACAGGGGGGGAGUGG 20 8241

BCLllA-8109 + GACUAAACAGGGGGGGAGUGG 21 8242

BCLllA-8110 + GGACUAAACAGGGGGGGAGUGG 22 8243

BCLllA-8111 + UGGACUAAACAGGGGGGGAGUGG 23 8244

BCLllA-8112 + GUGGACUAAACAGGGGGGGAGUGG 24 8245

BCLllA-8113 + AAUCCCAUGGAGAGGUGG 18 8246

BCLllA-8114 + GAAUCCCAUGGAGAGGUGG 19 8247

BCLllA-8115 + UGAAUCCCAUGGAGAGGUGG 20 8248

BCLllA-8116 + AUGAAUCCCAUGGAGAGGUGG 21 8249

BCLllA-8117 + UAUGAAUCCCAUGGAGAGGUGG 22 8250

BCLllA-8118 + AUAUGAAUCCCAUGGAGAGGUGG 23 8251

BCLllA-8119 + AAUAUGAAUCCCAUGGAGAGGUGG 24 8252

BCLllA-8120 + UGCAAUAUGAAUCCCAUG 18 8253

BCLllA-8121 + CUGCAAUAUGAAUCCCAUG 19 8254

BCLllA-8122 + UCUGCAAUAUGAAUCCCAUG 20 8255

BCLllA-8123 + GUCUGCAAUAUGAAUCCCAUG 21 8256

BCLllA-8124 + UGUCUGCAAUAUGAAUCCCAUG 22 8257

BCLllA-8125 + UUGUCUGCAAUAUGAAUCCCAUG 23 8258

BCLllA-8126 + AUUGUCUGCAAUAUGAAUCCCAUG 24 8259

BCLllA-8127 + CUCCUAGAGAAAUCCAUG 18 8260

BCLllA-8128 + UCUCCUAGAGAAAUCCAUG 19 8261 BCLllA-8129 + GUCUCCUAGAGAAAUCCAUG 20 8262

BCLllA-8130 + AGUCUCCUAGAGAAAUCCAUG 21 8263

BCLllA-8131 + AAGUCUCCUAGAGAAAUCCAUG 22 8264

BCLllA-8132 + UAAGUCUCCUAGAGAAAUCCAUG 23 8265

BCLllA-8133 + CUAAGUCUCCUAGAGAAAUCCAUG 24 8266

BCLllA-8134 + UCGGACUUGACCGUCAUG 18 8267

BCLllA-8135 + GUCGGACUUGACCGUCAUG 19 8268

BCLllA-6164 + CGUCGGACUUGACCGUCAUG 20 8269

BCLllA-8136 + UCGUCGGACUUGACCGUCAUG 21 8270

BCLllA-8137 + GUCGUCGGACUUGACCGUCAUG 22 8271

BCLllA-8138 + CGUCGUCGGACUUGACCGUCAUG 23 8272

BCLllA-8139 + CCGUCGUCGGACU UGACCGUCAUG 24 8273

BCLllA-8140 + CUUCUCGCCCAGGACCUG 18 8274

BCLllA-8141 + GCU UCUCGCCCAGGACCUG 19 8275

BCLllA-8142 + UGCUUCUCGCCCAGGACCUG 20 8276

BCLllA-8143 + AUGCUUCUCGCCCAGGACCUG 21 8277

BCLllA-8144 + UAUGCUUCUCGCCCAGGACCUG 22 8278

BCLllA-8145 + U UAUGCUUCUCGCCCAGGACCUG 23 8279

BCLllA-8146 + CUUAUGCUUCUCGCCCAGGACCUG 24 8280

BCLllA-8147 + AUUCUGCACCUAGUCCUG 18 8281

BCLllA-8148 + CAUUCUGCACCUAGUCCUG 19 8282

BCLllA-8149 + ACAUUCUGCACCUAGUCCUG 20 8283

BCLllA-8150 + GACAUUCUGCACCUAGUCCUG 21 8284

BCLllA-8151 + GGACAUUCUGCACCUAGUCCUG 22 8285

BCLllA-8152 + AGGACAUUCUGCACCUAGUCCUG 23 8286

BCLllA-8153 + AAGGACAUUCUGCACCUAGUCCUG 24 8287

BCLllA-6537 + GU UGUACAUGUGUAGCUG 18 8288

BCLllA-6538 + AGUUGUACAUGUGUAGCUG 19 8289

BCLllA-6539 + AAGUUGUACAUGUGUAGCUG 20 8290

BCLllA-6540 + CAAGUUGUACAUGUGUAGCUG 21 8291

BCLllA-6541 + GCAAGUUGUACAUGUGUAGCUG 22 8292

BCLllA-6542 + UGCAAGUUGUACAUGUGUAGCUG 23 8293

BCLllA-6543 + UUGCAAGUUGUACAUGUGUAGCUG 24 8294

BCLllA-8154 + GAGUACACGUUCUCCGUG 18 8295

BCLllA-8155 + CGAGUACACGUUCUCCGUG 19 8296

BCLllA-8156 + GCGAGUACACGUUCUCCGUG 20 8297

BCLllA-8157 + UGCGAGUACACGU UCUCCGUG 21 8298

BCLllA-8158 + CUGCGAGUACACGUUCUCCGUG 22 8299

BCLllA-8159 + ACUGCGAGUACACGUUCUCCGUG 23 8300

BCLllA-8160 + CACUGCGAGUACACGUUCUCCGUG 24 8301

BCLllA-8161 + CCAGCUCCCCGGGCGGUG 18 8302

BCLllA-8162 + UCCAGCUCCCCGGGCGGUG 19 8303 BCLllA-6177 + GUCCAGCUCCCCGGGCGGUG 20 8304

BCLllA-8163 + CGUCCAGCUCCCCGGGCGGUG 21 8305

BCLllA-8164 + CCGUCCAGCUCCCCGGGCGGUG 22 8306

BCLllA-8165 + UCCGUCCAGCUCCCCGGGCGGUG 23 8307

BCLllA-8166 + CUCCGUCCAGCUCCCCGGGCGGUG 24 8308

BCLllA-8167 + UCCGGGGAGCUGGCGGUG 18 8309

BCLllA-8168 + U UCCGGGGAGCUGGCGGUG 19 8310

BCLllA-8169 + GUUCCGGGGAGCUGGCGGUG 20 8311

BCLllA-8170 + GGU UCCGGGGAGCUGGCGGUG 21 8312

BCLllA-8171 + GGGUUCCGGGGAGCUGGCGGUG 22 8313

BCLllA-8172 + CGGGU UCCGGGGAGCUGGCGGUG 23 8314

BCLllA-8173 + CCGGGUUCCGGGGAGCUGGCGGUG 24 8315

BCLllA-8174 + CCAAGUGAUGUCUCGGUG 18 8316

BCLllA-8175 + UCCAAGUGAUGUCUCGGUG 19 8317

BCLllA-8176 + GUCCAAGUGAUGUCUCGGUG 20 8318

BCLllA-8177 + GGUCCAAGUGAUGUCUCGGUG 21 8319

BCLllA-8178 + GGGUCCAAGUGAUGUCUCGGUG 22 8320

BCLllA-8179 + GGGGUCCAAGUGAUGUCUCGGUG 23 8321

BCLllA-8180 + GGGGGUCCAAGUGAUGUCUCGGUG 24 8322

BCLllA-8181 + AGCUCCCCGGGCGGUGUG 18 8323

BCLllA-8182 + CAGCUCCCCGGGCGGUGUG 19 8324

BCLllA-8183 + CCAGCUCCCCGGGCGGUGUG 20 8325

BCLllA-8184 + UCCAGCUCCCCGGGCGGUGUG 21 8326

BCLllA-8185 + GUCCAGCUCCCCGGGCGGUGUG 22 8327

BCLllA-8186 + CGUCCAGCUCCCCGGGCGGUGUG 23 8328

BCLllA-8187 + CCGUCCAGCUCCCCGGGCGGUGUG 24 8329

BCLllA-8188 + GCCGAAUGGGGGUGUGUG 18 8330

BCLllA-8189 + CGCCGAAUGGGGGUGUGUG 19 8331

BCLllA-8190 + ACGCCGAAUGGGGGUGUGUG 20 8332

BCLllA-8191 + UACGCCGAAUGGGGGUGUGUG 21 8333

BCLllA-8192 + CUACGCCGAAUGGGGGUGUGUG 22 8334

BCLllA-8193 + ACUACGCCGAAUGGGGGUGUGUG 23 8335

BCLllA-8194 + UACUACGCCGAAUGGGGGUGUGUG 24 8336

BCLllA-8195 + GGGAGGAGGGGCGGAU UG 18 8337

BCLllA-8196 + AGGGAGGAGGGGCGGAUUG 19 8338

BCLllA-8197 + GAGGGAGGAGGGGCGGAUUG 20 8339

BCLllA-8198 + GGAGGGAGGAGGGGCGGAUUG 21 8340

BCLllA-8199 + GGGAGGGAGGAGGGGCGGAUUG 22 8341

BCLllA-8200 + UGGGAGGGAGGAGGGGCGGAUUG 23 8342

BCLllA-8201 + CUGGGAGGGAGGAGGGGCGGAUUG 24 8343

BCLllA-8202 + UCGCACAGGUUGCACUUG 18 8344

BCLllA-8203 + GUCGCACAGGUUGCACUUG 19 8345 BCLllA-8204 + GGUCGCACAGGUUGCACUUG 20 8346

BCLllA-8205 + UGGUCGCACAGGUUGCACUUG 21 8347

BCLllA-8206 + GUGGUCGCACAGGUUGCACUUG 22 8348

BCLllA-8207 + CGUGGUCGCACAGGUUGCACUUG 23 8349

BCLllA-8208 + GCGUGGUCGCACAGGUUGCACUUG 24 8350

BCLllA-8209 + ACCAGGUUGCUCUGAAAU 18 8351

BCLllA-8210 + CACCAGGUUGCUCUGAAAU 19 8352

BCLllA-8211 + CCACCAGGU UGCUCUGAAAU 20 8353

BCLllA-8212 + ACCACCAGGUUGCUCUGAAAU 21 8354

BCLllA-8213 + CACCACCAGGU UGCUCUGAAAU 22 8355

BCLllA-8214 + GCACCACCAGGUUGCUCUGAAAU 23 8356

BCLllA-8215 + UGCACCACCAGGUUGCUCUGAAAU 24 8357

BCLllA-8216 + CGGGCCCGGACCACUAAU 18 8358

BCLllA-8217 + CCGGGCCCGGACCACUAAU 19 8359

BCLllA-8218 + CCCGGGCCCGGACCACUAAU 20 8360

BCLllA-8219 + GCCCGGGCCCGGACCACUAAU 21 8361

BCLllA-8220 + UGCCCGGGCCCGGACCACUAAU 22 8362

BCLllA-8221 + CUGCCCGGGCCCGGACCACUAAU 23 8363

BCLllA-8222 + CCUGCCCGGGCCCGGACCACUAAU 24 8364

BCLllA-8223 + GGGCUCUCGAGCUUCCAU 18 8365

BCLllA-8224 + AGGGCUCUCGAGCUUCCAU 19 8366

BCLllA-8225 + AAGGGCUCUCGAGCUUCCAU 20 8367

BCLllA-8226 + UAAGGGCUCUCGAGCUUCCAU 21 8368

BCLllA-8227 + UUAAGGGCUCUCGAGCU UCCAU 22 8369

BCLllA-8228 + CUUAAGGGCUCUCGAGCUUCCAU 23 8370

BCLllA-8229 + ACU UAAGGGCUCUCGAGCUUCCAU 24 8371

BCLllA-8230 + GUCGGACUUGACCGUCAU 18 8372

BCLllA-8231 + CGUCGGACUUGACCGUCAU 19 8373

BCLllA-6186 + UCGUCGGACUUGACCGUCAU 20 8374

BCLllA-8232 + GUCGUCGGACUUGACCGUCAU 21 8375

BCLllA-8233 + CGUCGUCGGACUUGACCGUCAU 22 8376

BCLllA-8234 + CCGUCGUCGGACU UGACCGUCAU 23 8377

BCLllA-8235 + ACCGUCGUCGGACUUGACCGUCAU 24 8378

BCLllA-8236 + AUAGGGCUGGGCCGGCCU 18 8379

BCLllA-8237 + CAUAGGGCUGGGCCGGCCU 19 8380

BCLllA-6198 + GCAUAGGGCUGGGCCGGCCU 20 8381

BCLllA-8238 + UGCAUAGGGCUGGGCCGGCCU 21 8382

BCLllA-8239 + UUGCAUAGGGCUGGGCCGGCCU 22 8383

BCLllA-8240 + U UUGCAUAGGGCUGGGCCGGCCU 23 8384

BCLllA-8241 + CUUUGCAUAGGGCUGGGCCGGCCU 24 8385

BCLllA-8242 + UCUGGAGUCUCCGAAGCU 18 8386

BCLllA-8243 + GUCUGGAGUCUCCGAAGCU 19 8387 BCLllA-8244 + UGUCUGGAGUCUCCGAAGCU 20 8388

BCLllA-8245 + UUGUCUGGAGUCUCCGAAGCU 21 8389

BCLllA-8246 + AUUGUCUGGAGUCUCCGAAGCU 22 8390

BCLllA-8247 + GAUUGUCUGGAGUCUCCGAAGCU 23 8391

BCLllA-8248 + CGAUUGUCUGGAGUCUCCGAAGCU 24 8392

BCLllA-8249 + UCUCGAGCUUGAUGCGCU 18 8393

BCLllA-8250 + UUCUCGAGCUUGAUGCGCU 19 8394

BCLllA-8251 + CUUCUCGAGCUUGAUGCGCU 20 8395

BCLllA-8252 + CCUUCUCGAGCUUGAUGCGCU 21 8396

BCLllA-8253 + UCCU UCUCGAGCUUGAUGCGCU 22 8397

BCLllA-8254 + CUCCUUCUCGAGCUUGAUGCGCU 23 8398

BCLllA-8255 + ACUCCUUCUCGAGCUUGAUGCGCU 24 8399

BCLllA-8256 + UGGACUUGACCGGGGGCU 18 8400

BCLllA-8257 + UUGGACUUGACCGGGGGCU 19 8401

BCLllA-6207 + CUUGGACUUGACCGGGGGCU 20 8402

BCLllA-8258 + ACUUGGACUUGACCGGGGGCU 21 8403

BCLllA-8259 + GACUUGGACUUGACCGGGGGCU 22 8404

BCLllA-8260 + UGACUUGGACUUGACCGGGGGCU 23 8405

BCLllA-8261 + AUGACUUGGACUUGACCGGGGGCU 24 8406

BCLllA-8262 + UCCCAUGGAGAGGUGGCU 18 8407

BCLllA-8263 + AUCCCAUGGAGAGGUGGCU 19 8408

BCLllA-6208 + AAUCCCAUGGAGAGGUGGCU 20 8409

BCLllA-8264 + GAAUCCCAUGGAGAGGUGGCU 21 8410

BCLllA-8265 + UGAAUCCCAUGGAGAGGUGGCU 22 8411

BCLllA-8266 + AUGAAUCCCAUGGAGAGGUGGCU 23 8412

BCLllA-8267 + UAUGAAUCCCAUGGAGAGGUGGCU 24 8413

BCLllA-8268 + GUGCACCACCAGGUUGCU 18 8414

BCLllA-8269 + GGUGCACCACCAGGUUGCU 19 8415

BCLllA-8270 + CGGUGCACCACCAGGUUGCU 20 8416

BCLllA-8271 + CCGGUGCACCACCAGGU UGCU 21 8417

BCLllA-8272 + GCCGGUGCACCACCAGGUUGCU 22 8418

BCLllA-8273 + CGCCGGUGCACCACCAGGU UGCU 23 8419

BCLllA-8274 + GCGCCGGUGCACCACCAGGUUGCU 24 8420

BCLllA-8275 + AAGCUAAGGAAGGGAUCU 18 8421

BCLllA-8276 + GAAGCUAAGGAAGGGAUCU 19 8422

BCLllA-8277 + CGAAGCUAAGGAAGGGAUCU 20 8423

BCLllA-8278 + CCGAAGCUAAGGAAGGGAUCU 21 8424

BCLllA-8279 + UCCGAAGCUAAGGAAGGGAUCU 22 8425

BCLllA-8280 + CUCCGAAGCUAAGGAAGGGAUCU 23 8426

BCLllA-8281 + UCUCCGAAGCUAAGGAAGGGAUCU 24 8427

BCLllA-8282 + GGCGAUUGUCUGGAGUCU 18 8428

BCLllA-8283 + AGGCGAUUGUCUGGAGUCU 19 8429 BCLllA-8284 + AAGGCGAUUGUCUGGAGUCU 20 8430

BCLllA-8285 + AAAGGCGAUUGUCUGGAGUCU 21 8431

BCLllA-8286 + AAAAGGCGAUUGUCUGGAGUCU 22 8432

BCLllA-8287 + CAAAAGGCGAUUGUCUGGAGUCU 23 8433

BCLllA-8288 + GCAAAAGGCGAUUGUCUGGAGUCU 24 8434

BCLllA-8289 + CCUCCUCGUCCCCGUUCU 18 8435

BCLllA-8290 + UCCUCCUCGUCCCCGUUCU 19 8436

BCLllA-8291 + U UCCUCCUCGUCCCCGU UCU 20 8437

BCLllA-8292 + CUUCCUCCUCGUCCCCGUUCU 21 8438

BCLllA-8293 + UCUUCCUCCUCGUCCCCGU UCU 22 8439

BCLllA-8294 + CUCUUCCUCCUCGUCCCCGUUCU 23 8440

BCLllA-8295 + CCUCUUCCUCCUCGUCCCCGUUCU 24 8441

BCLllA-8296 + AG CG CAAAC U CCCGUUCU 18 8442

BCLllA-8297 + AAGCGCAAACUCCCGUUCU 19 8443

BCLllA-8298 + GAAGCGCAAACUCCCGUUCU 20 8444

BCLllA-8299 + AGAAGCGCAAACUCCCGUUCU 21 8445

BCLllA-8300 + GAGAAGCGCAAACUCCCGUUCU 22 8446

BCLllA-8301 + GGAGAAGCGCAAACUCCCGUUCU 23 8447

BCLllA-8302 + UGGAGAAGCGCAAACUCCCGUUCU 24 8448

BCLllA-8303 + GGGGGCU UCAAAUU UUCU 18 8449

BCLllA-8304 + UGGGGGCUUCAAAUUU UCU 19 8450

BCLllA-8305 + CUGGGGGCUUCAAAUUUUCU 20 8451

BCLllA-8306 + CCUGGGGGCUUCAAAUUUUCU 21 8452

BCLllA-8307 + CCCUGGGGGCUUCAAAUUUUCU 22 8453

BCLllA-8308 + CCCCUGGGGGCU UCAAAUUUUCU 23 8454

BCLllA-8309 + ACCCCUGGGGGCUUCAAAUUUUCU 24 8455

BCLllA-8310 + AAGAACCUAGAAAGAGGU 18 8456

BCLllA-8311 + GAAGAACCUAGAAAGAGGU 19 8457

BCLllA-6224 + UGAAGAACCUAGAAAGAGGU 20 8458

BCLllA-8312 + GUGAAGAACCUAGAAAGAGGU 21 8459

BCLllA-8313 + UGUGAAGAACCUAGAAAGAGGU 22 8460

BCLllA-8314 + GUGUGAAGAACCUAGAAAGAGGU 23 8461

BCLllA-8315 + UGUGUGAAGAACCUAGAAAGAGGU 24 8462

BCLllA-8316 + UCCAGCUCCCCGGGCGGU 18 8463

BCLllA-8317 + GUCCAGCUCCCCGGGCGGU 19 8464

BCLllA-8318 + CGUCCAGCUCCCCGGGCGGU 20 8465

BCLllA-8319 + CCGUCCAGCUCCCCGGGCGGU 21 8466

BCLllA-8320 + UCCGUCCAGCUCCCCGGGCGGU 22 8467

BCLllA-8321 + CUCCGUCCAGCUCCCCGGGCGGU 23 8468

BCLllA-8322 + CCUCCGUCCAGCUCCCCGGGCGGU 24 8469

BCLllA-8323 + GAUACCAACCCGCGGGGU 18 8470

BCLllA-8324 + GGAUACCAACCCGCGGGGU 19 8471 BCLllA-8325 + GGGAUACCAACCCGCGGGGU 20 8472

BCLllA-8326 + AGGGAUACCAACCCGCGGGGU 21 8473

BCLllA-8327 + AAGGGAUACCAACCCGCGGGGU 22 8474

BCLllA-8328 + GAAGGGAUACCAACCCGCGGGGU 23 8475

BCLllA-8329 + UGAAGGGAUACCAACCCGCGGGGU 24 8476

BCLllA-8330 + UACGCCGAAUGGGGGUGU 18 8477

BCLllA-8331 + CUACGCCGAAUGGGGGUGU 19 8478

BCLllA-8332 + ACUACGCCGAAUGGGGGUGU 20 8479

BCLllA-8333 + UACUACGCCGAAUGGGGGUGU 21 8480

BCLllA-8334 + GUACUACGCCGAAUGGGGGUGU 22 8481

BCLllA-8335 + GGU ACUACGCCGAAUGGGGGUGU 23 8482

BCLllA-8336 + GGGUACUACGCCGAAUGGGGGUGU 24 8483

BCLllA-8337 + GAGGCAAAAGGCGAUUGU 18 8484

BCLllA-8338 + GGAGGCAAAAGGCGAUUGU 19 8485

BCLllA-8339 + AGGAGGCAAAAGGCGAU UGU 20 8486

BCLllA-8340 + GAGGAGGCAAAAGGCGAUUGU 21 8487

BCLllA-8341 + CGAGGAGGCAAAAGGCGAUUGU 22 8488

BCLllA-8342 + ACGAGGAGGCAAAAGGCGAUUGU 23 8489

BCLllA-8343 + GACGAGGAGGCAAAAGGCGAUUGU 24 8490

BCLllA-8344 + CAAAUUUUCUCAGAACUU 18 8491

BCLllA-8345 + UCAAAUUUUCUCAGAACUU 19 8492

BCLllA-8346 + U UCAAAUUUUCUCAGAACUU 20 8493

BCLllA-8347 + CU U CAAAU U U U CU CAG AACU U 21 8494

BCLllA-8348 + GCU UCAAAUUUUCUCAGAACUU 22 8495

BCLllA-8349 + GGCU UCAAAUUUUCUCAGAACUU 23 8496

BCLllA-8350 + GGGCUUCAAAUUUUCUCAGAACUU 24 8497

BCLllA-8351 + CGCUGCGUCUGCCCUCU U 18 8498

BCLllA-8352 + UCGCUGCGUCUGCCCUCUU 19 8499

BCLllA-8353 + GUCGCUGCGUCUGCCCUCUU 20 8500

BCLllA-8354 + UGUCGCUGCGUCUGCCCUCUU 21 8501

BCLllA-8355 + GUGUCGCUGCGUCUGCCCUCUU 22 8502

BCLllA-8356 + AGUGUCGCUGCGUCUGCCCUCUU 23 8503

BCLllA-8357 + AAGUGUCGCUGCGUCUGCCCUCUU 24 8504

BCLllA-8358 + AGUCGCUGGUGCCGGGUU 18 8505

BCLllA-8359 + AAGUCGCUGGUGCCGGGUU 19 8506

BCLllA-8360 + CAAGUCGCUGGUGCCGGGUU 20 8507

BCLllA-8361 + CCAAGUCGCUGGUGCCGGGUU 21 8508

BCLllA-8362 + ACCAAGUCGCUGGUGCCGGGUU 22 8509

BCLllA-8363 + CACCAAGUCGCUGGUGCCGGGUU 23 8510

BCLllA-8364 + CCACCAAGUCGCUGGUGCCGGGUU 24 8511

BCLllA-8365 + CUGCCCAGCAGCAGCU UU 18 8512

BCLllA-8366 + GCUGCCCAGCAGCAGCU UU 19 8513 BCLllA-8367 + GGCUGCCCAGCAGCAGCUUU 20 8514

BCLllA-8368 + GGGCUGCCCAGCAGCAGCUUU 21 8515

BCLllA-8369 + GGGGCUGCCCAGCAGCAGCUUU 22 8516

BCLllA-8370 + UGGGGCUGCCCAGCAGCAGCUUU 23 8517

BCLllA-8371 + CUGGGGCUGCCCAGCAGCAGCUUU 24 8518

BCLllA-8372 - GGCAGGCCCAGCU C A A A A 18 8519

BCLllA-8373 - GGGCAGGCCCAGCUCAAAA 19 8520

BCLllA-8374 - CGGGCAGGCCCAGCU C A A A A 20 8521

BCLllA-8375 - CCGGGCAGGCCCAGCUCAAAA 21 8522

BCLllA-8376 - CCCGGGCAGGCCCAGCUCAAAA 22 8523

BCLllA-8377 - GCCCGGGCAGGCCCAGCUCAAAA 23 8524

BCLllA-8378 - GGCCCGGGCAGGCCCAGCUCAAAA 24 8525

BCLllA-8379 - UAAGAAUCUACUUAGAAA 18 8526

BCLllA-8380 - U U AAG AAU CU ACU U AG AAA 19 8527

BCLllA-8381 - AUUAAGAAUCUACUUAGAAA 20 8528

BCLllA-8382 - GAUUAAGAAUCUACUUAGAAA 21 8529

BCLllA-8383 - GGAUUAAGAAUCUACUUAGAAA 22 8530

BCLllA-8384 - UGGAUUAAGAAUCUACUUAGAAA 23 8531

BCLllA-8385 - AUGGAUUAAGAAUCUACUUAGAAA 24 8532

BCLllA-8386 - CGGGCAGGCCCAGCUCAA 18 8533

BCLllA-8387 - CCGGGCAGGCCCAGCUCAA 19 8534

BCLllA-8388 - CCCGGGCAGGCCCAGCUCAA 20 8535

BCLllA-8389 - GCCCGGGCAGGCCCAGCUCAA 21 8536

BCLllA-8390 - GGCCCGGGCAGGCCCAGCUCAA 22 8537

BCLllA-8391 - GGGCCCGGGCAGGCCCAGCUCAA 23 8538

BCLllA-8392 - CGGGCCCGGGCAGGCCCAGCUCAA 24 8539

BCLllA-8393 - GACGAGGAAGAGGAAGAA 18 8540

BCLllA-8394 - CGACGAGGAAGAGGAAGAA 19 8541

BCLllA-3947 - ACGACGAGGAAGAGGAAGAA 20 8542

BCLllA-8395 - GACGACGAGGAAGAGGAAGAA 21 8543

BCLllA-8396 - GGACGACGAGGAAGAGGAAGAA 22 8544

BCLllA-8397 - AGGACGACGAGGAAGAGGAAGAA 23 8545

BCLllA-8398 - GAGGACGACGAGGAAGAGGAAGAA 24 8546

BCLllA-8399 - CAACCUGAUCCCGGAGAA 18 8547

BCLllA-8400 - CCAACCUGAUCCCGGAGAA 19 8548

BCLllA-5881 - CCCAACCUGAUCCCGGAGAA 20 8549

BCLllA-8401 - CCCCAACCUGAUCCCGGAGAA 21 8550

BCLllA-8402 - ACCCCAACCUGAUCCCGGAGAA 22 8551

BCLllA-8403 - GACCCCAACCUGAUCCCGGAGAA 23 8552

BCLllA-8404 - CGACCCCAACCUGAUCCCGGAGAA 24 8553

BCLllA-8405 - GGAGCACUCCUCGGAGAA 18 8554

BCLllA-8406 - CGGAGCACUCCUCGGAGAA 19 8555 BCLllA-5882 - UCGGAGCACUCCUCGGAGAA 20 8556

BCLllA-8407 - GUCGGAGCACUCCUCGGAGAA 21 8557

BCLllA-8408 - CGUCGGAGCACUCCUCGGAGAA 22 8558

BCLllA-8409 - UCGUCGGAGCACUCCUCGGAGAA 23 8559

BCLllA-8410 - CUCGUCGGAGCACUCCUCGGAGAA 24 8560

BCLllA-8411 - GAGGAGGACGACGAGGAA 18 8561

BCLllA-8412 - AGAGGAGGACGACGAGGAA 19 8562

BCLllA-3950 - AAGAGGAGGACGACGAGGAA 20 8563

BCLllA-8413 - GAAGAGGAGGACGACGAGGAA 21 8564

BCLllA-8414 - GGAAGAGGAGGACGACGAGGAA 22 8565

BCLllA-8415 - AGGAAGAGGAGGACGACGAGGAA 23 8566

BCLllA-8416 - GAGGAAGAGGAGGACGACGAGGAA 24 8567

BCLllA-8417 - GAGGAAGAAGAGGAGGAA 18 8568

BCLllA-8418 - AGAGGAAGAAGAGGAGGAA 19 8569

BCLllA-3962 - AAGAGGAAGAAGAGGAGGAA 20 8570

BCLllA-8419 - GAAGAGGAAGAAGAGGAGGAA 21 8571

BCLllA-8420 - GGAAGAGGAAGAAGAGGAGGAA 22 8572

BCLllA-8421 - AGGAAGAGGAAGAAGAGGAGGAA 23 8573

BCLllA-8422 - GAGGAAGAGGAAGAAGAGGAGGAA 24 8574

BCLllA-8423 - AACGGGGACGAGGAGGAA 18 8575

BCLllA-8424 - GAACGGGGACGAGGAGGAA 19 8576

BCLllA-3934 - AGAACGGGGACGAGGAGGAA 20 8577

BCLllA-8425 - GAGAACGGGGACGAGGAGGAA 21 8578

BCLllA-8426 - GGAGAACGGGGACGAGGAGGAA 22 8579

BCLllA-8427 - CGGAGAACGGGGACGAGGAGGAA 23 8580

BCLllA-8428 - CCGGAGAACGGGGACGAGGAGGAA 24 8581

BCLllA-8429 - GGCGCAGCGGCACGGGAA 18 8582

BCLllA-8430 - GGGCGCAGCGGCACGGGAA 19 8583

BCLllA-3857 - GGGGCGCAGCGGCACGGGAA 20 8584

BCLllA-8431 - CGGGGCGCAGCGGCACGGGAA 21 8585

BCLllA-8432 - UCGGGGCGCAGCGGCACGGGAA 22 8586

BCLllA-8433 - CUCGGGGCGCAGCGGCACGGGAA 23 8587

BCLllA-8434 - UCUCGGGGCGCAGCGGCACGGGAA 24 8588

BCLllA-8435 - CGGCCGCGAUGCCCAACA 18 8589

BCLllA-8436 - CCGGCCGCGAUGCCCAACA 19 8590

BCLllA-5893 - CCCGGCCGCGAUGCCCAACA 20 8591

BCLllA-8437 - CCCCGGCCGCGAUGCCCAACA 21 8592

BCLllA-8438 - CCCCCGGCCGCGAUGCCCAACA 22 8593

BCLllA-8439 - GCCCCCGGCCGCGAUGCCCAACA 23 8594

BCLllA-8440 - UGCCCCCGGCCGCGAUGCCCAACA 24 8595

BCLllA-8441 - CUACUUAGAAAGCGAACA 18 8596

BCLllA-8442 - U CU ACU U AG AAAG CG AACA 19 8597 BCLllA-5894 - AUCUACUUAGAAAGCGAACA 20 8598

BCLllA-8443 - AAUCUACUUAGAAAGCGAACA 21 8599

BCLllA-8444 - GAAUCUACUUAGAAAGCGAACA 22 8600

BCLllA-8445 - AGAAUCUACUUAGAAAGCGAACA 23 8601

BCLllA-8446 - AAGAAUCUACUUAGAAAGCGAACA 24 8602

BCLllA-8447 - CCCCUGUUUAGUCCACCA 18 8603

BCLllA-8448 - CCCCCUGUUUAGUCCACCA 19 8604

BCLllA-8449 - CCCCCCUGUUUAGUCCACCA 20 8605

BCLllA-8450 - CCCCCCCUGUUUAGUCCACCA 21 8606

BCLllA-8451 - UCCCCCCCUGUUUAGUCCACCA 22 8607

BCLllA-8452 - CUCCCCCCCUGUUUAGUCCACCA 23 8608

BCLllA-8453 - ACUCCCCCCCUGUUUAGUCCACCA 24 8609

BCLllA-8454 - CAUUCGGCGUAGUACCCA 18 8610

BCLllA-8455 - CCAUUCGGCGUAGUACCCA 19 8611

BCLllA-8456 - CCCAUUCGGCGUAGUACCCA 20 8612

BCLllA-8457 - CCCCAUUCGGCGUAGUACCCA 21 8613

BCLllA-8458 - CCCCCAUUCGGCGUAGUACCCA 22 8614

BCLllA-8459 - ACCCCCAUUCGGCGUAGUACCCA 23 8615

BCLllA-8460 - CACCCCCAUUCGGCGUAGUACCCA 24 8616

BCLllA-8461 - GGCCGAGGCCGAGGGCCA 18 8617

BCLllA-8462 - UGGCCGAGGCCGAGGGCCA 19 8618

BCLllA-8463 - CUGGCCGAGGCCGAGGGCCA 20 8619

BCLllA-8464 - CCUGGCCGAGGCCGAGGGCCA 21 8620

BCLllA-8465 - ACCUGGCCGAGGCCGAGGGCCA 22 8621

BCLllA-8466 - CACCUGGCCGAGGCCGAGGGCCA 23 8622

BCLllA-8467 - CCACCUGGCCGAGGCCGAGGGCCA 24 8623

BCLllA-8468 - UUUCUCUUGCAACACGCA 18 8624

BCLllA-8469 - GUUUCUCUUGCAACACGCA 19 8625

BCLllA-8470 - GGUUUCUCUUGCAACACGCA 20 8626

BCLllA-8471 - UGGUUUCUCUUGCAACACGCA 21 8627

BCLllA-8472 - AUGGUUUCUCUUGCAACACGCA 22 8628

BCLllA-8473 - CAUGGUUUCUCUUGCAACACGCA 23 8629

BCLllA-8474 - GCAUGGUUUCUCUUGCAACACGCA 24 8630

BCLllA-8475 - ACUUGGACCCCCACCGCA 18 8631

BCLllA-8476 - CACUUGGACCCCCACCGCA 19 8632

BCLllA-8477 - UCACUUGGACCCCCACCGCA 20 8633

BCLllA-8478 - AUCACUUGGACCCCCACCGCA 21 8634

BCLllA-8479 - CAUCACUUGGACCCCCACCGCA 22 8635

BCLllA-8480 - ACAUCACUUGGACCCCCACCGCA 23 8636

BCLllA-8481 - GACAUCACUUGGACCCCCACCGCA 24 8637

BCLllA-8482 - UCUCGGGGCGCAGCGGCA 18 8638

BCLllA-8483 - AUCUCGGGGCGCAGCGGCA 19 8639 BCLllA-5904 - GAUCUCGGGGCGCAGCGGCA 20 8640

BCLllA-8484 - GGAUCUCGGGGCGCAGCGGCA 21 8641

BCLllA-8485 - GGGAUCUCGGGGCGCAGCGGCA 22 8642

BCLllA-8486 - AGGGAUCUCGGGGCGCAGCGGCA 23 8643

BCLllA-8487 - GAGGGAUCUCGGGGCGCAGCGGCA 24 8644

BCLllA-8488 - AGACUUAGAGAGCUGGCA 18 8645

BCLllA-8489 - GAGACUUAGAGAGCUGGCA 19 8646

BCLllA-5907 - GGAGACUUAGAGAGCUGGCA 20 8647

BCLllA-8490 - AGGAGACUUAGAGAGCUGGCA 21 8648

BCLllA-8491 - UAGGAGACUUAGAGAGCUGGCA 22 8649

BCLllA-8492 - CUAGGAGACUUAGAGAGCUGGCA 23 8650

BCLllA-8493 - UCUAGGAGACUUAGAGAGCUGGCA 24 8651

BCLllA-8494 - GCUCCAUGCAGCACUUCA 18 8652

BCLllA-8495 - AGCUCCAUGCAGCACUUCA 19 8653

BCLllA-8496 - CAGCUCCAUGCAGCACUUCA 20 8654

BCLllA-8497 - UCAGCUCCAUGCAGCACUUCA 21 8655

BCLllA-8498 - CUCAGCUCCAUGCAGCACUUCA 22 8656

BCLllA-8499 - GCUCAGCUCCAUGCAGCACUUCA 23 8657

BCLllA-8500 - UGCUCAGCUCCAUGCAGCACUUCA 24 8658

BCLllA-8501 - UGGUGGCCAAGUUCAAGA 18 8659

BCLllA-8502 - G UGGUGGCCAAG U U CAAGA 19 8660

BCLllA-8503 - CGUGGUGGCCAAGUUCAAGA 20 8661

BCLllA-8504 - CCGUGGUGGCCAAGUUCAAGA 21 8662

BCLllA-8505 - UCCGUGGUGGCCAAGUUCAAGA 22 8663

BCLllA-8506 - GUCCGUGGUGGCCAAGUUCAAGA 23 8664

BCLllA-8507 - AGUCCGUGGUGGCCAAGUUCAAGA 24 8665

BCLllA-8508 - AGGAGGAGCUGACGGAGA 18 8666

BCLllA-8509 - GAGGAGGAGCUGACGGAGA 19 8667

BCLllA-8510 - GGAGGAGGAGCUGACGGAGA 20 8668

BCLllA-8511 - AGGAGGAGGAGCUGACGGAGA 21 8669

BCLllA-8512 - GAGGAGGAGGAGCUGACGGAGA 22 8670

BCLllA-8513 - GGAGGAGGAGGAGCUGACGGAGA 23 8671

BCLllA-8514 - AGGAGGAGGAGGAGCUGACGGAGA 24 8672

BCLllA-8515 - CCAACCUGAUCCCGGAGA 18 8673

BCLllA-8516 - CCCAACCUGAUCCCGGAGA 19 8674

BCLllA-8517 - CCCCAACCUGAUCCCGGAGA 20 8675

BCLllA-8518 - ACCCCAACCUGAUCCCGGAGA 21 8676

BCLllA-8519 - GACCCCAACCUGAUCCCGGAGA 22 8677

BCLllA-8520 - CGACCCCAACCUGAUCCCGGAGA 23 8678

BCLllA-8521 - ACGACCCCAACCUGAUCCCGGAGA 24 8679

BCLllA-8522 - CGGAGCACUCCUCGGAGA 18 8680

BCLllA-8523 - UCGGAGCACUCCUCGGAGA 19 8681 BCLllA-8524 - GUCGGAGCACUCCUCGGAGA 20 8682

BCLllA-8525 - CGUCGGAGCACUCCUCGGAGA 21 8683

BCLllA-8526 - UCGUCGGAGCACUCCUCGGAGA 22 8684

BCLllA-8527 - CUCGUCGGAGCACUCCUCGGAGA 23 8685

BCLllA-8528 - CCUCGUCGGAGCACUCCUCGGAGA 24 8686

BCLllA-8529 - UACCAGGAUCAGUAUCGA 18 8687

BCLllA-8530 - AUACCAGGAUCAGUAUCGA 19 8688

BCLllA-8531 - AAUACCAGGAUCAGUAUCGA 20 8689

BCLllA-8532 - GAAUACCAGGAUCAGUAUCGA 21 8690

BCLllA-8533 - AGAAUACCAGGAUCAGUAUCGA 22 8691

BCLllA-8534 - AAGAAUACCAGGAUCAGUAUCGA 23 8692

BCLllA-8535 - UAAGAAUACCAGGAUCAGUAUCGA 24 8693

BCLllA-8536 - UGUGUGGCAGUUUUCGGA 18 8694

BCLllA-8537 - AUGUGUGGCAGUUUUCGGA 19 8695

BCLllA-5929 - GAUGUGUGGCAGUUUUCGGA 20 8696

BCLllA-8538 - AGAUGUGUGGCAGUUUUCGGA 21 8697

BCLllA-8539 - AAGAUGUGUGGCAGUUUUCGGA 22 8698

BCLllA-8540 - CAAGAUGUGUGGCAGUUUUCGGA 23 8699

BCLllA-8541 - UCAAGAUGUGUGGCAGUUUUCGGA 24 8700

BCLllA-8542 - ACCGCCCGGGGAGCUGGA 18 8701

BCLllA-8543 - CACCGCCCGGGGAGCUGGA 19 8702

BCLllA-5933 - ACACCGCCCGGGGAGCUGGA 20 8703

BCLllA-8544 - CACACCGCCCGGGGAGCUGGA 21 8704

BCLllA-8545 - CCACACCGCCCGGGGAGCUGGA 22 8705

BCLllA-8546 - UCCACACCGCCCGGGGAGCUGGA 23 8706

BCLllA-8547 - CUCCACACCGCCCGGGGAGCUGGA 24 8707

BCLllA-8548 - AGCGGCACGGGAAGUGGA 18 8708

BCLllA-8549 - CAGCGGCACGGGAAGUGGA 19 8709

BCLllA-5934 - GCAGCGGCACGGGAAGUGGA 20 8710

BCLllA-8550 - CGCAGCGGCACGGGAAGUGGA 21 8711

BCLllA-8551 - GCGCAGCGGCACGGGAAGUGGA 22 8712

BCLllA-8552 - GGCGCAGCGGCACGGGAAGUGGA 23 8713

BCLllA-8553 - GGGCGCAGCGGCACGGGAAGUGGA 24 8714

BCLllA-8554 - AGGAGGAGGAGGAGCUGA 18 8715

BCLllA-8555 - GAGGAGGAGGAGGAGCUGA 19 8716

BCLllA-5938 - AGAGGAGGAGGAGGAGCUGA 20 8717

BCLllA-8556 - AAGAGGAGGAGGAGGAGCUGA 21 8718

BCLllA-8557 - GAAGAGGAGGAGGAGGAGCUGA 22 8719

BCLllA-8558 - GGAAGAGGAGGAGGAGGAGCUGA 23 8720

BCLllA-8559 - AGGAAGAGGAGGAGGAGGAGCUGA 24 8721

BCLllA-8560 - GGUUGAAUCCAAUGGCUA 18 8722

BCLllA-8561 - CGGUUGAAUCCAAUGGCUA 19 8723 BCLllA-5944 - GCGGUUGAAUCCAAUGGCUA 20 8724

BCLllA-8562 - UGCGGUUGAAUCCAAUGGCUA 21 8725

BCLllA-8563 - CUGCGGUUGAAUCCAAUGGCUA 22 8726

BCLllA-8564 - GCUGCGGUUGAAUCCAAUGGCUA 23 8727

BCLllA-8565 - UGCUGCGGUUGAAUCCAAUGGCUA 24 8728

BCLllA-8566 - AGAAUACCAGGAUCAGUA 18 8729

BCLllA-8567 - AAGAAUACCAGGAUCAGUA 19 8730

BCLllA-8568 - UAAGAAUACCAGGAUCAGUA 20 8731

BCLllA-8569 - CUAAGAAUACCAGGAUCAGUA 21 8732

BCLllA-8570 - G CU AAG AAU ACCAGG AU CAG U A 22 8733

BCLllA-8571 - UGCU AAGAAUACCAGGAUCAGUA 23 8734

BCLllA-8572 - CUGCUAAGAAUACCAGGAUCAGUA 24 8735

BCLllA-8573 - AUUUCUCUAGGAGACUUA 18 8736

BCLllA-8574 - GAUUUCUCUAGGAGACUUA 19 8737

BCLllA-8575 - GGAUUUCUCUAGGAGACUUA 20 8738

BCLllA-8576 - UGGAUUUCUCUAGGAGACUUA 21 8739

BCLllA-8577 - AUGGAUUUCUCUAGGAGACUUA 22 8740

BCLllA-8578 - CAUGGAUUUCUCUAGGAGACUUA 23 8741

BCLllA-8579 - CCAUGGAUUUCUCUAGGAGACUUA 24 8742

BCLllA-8580 - CCGGCCGCGAUGCCCAAC 18 8743

BCLllA-8581 - CCCGGCCGCGAUGCCCAAC 19 8744

BCLllA-8582 - CCCCGGCCGCGAUGCCCAAC 20 8745

BCLllA-8583 - CCCCCGGCCGCGAUGCCCAAC 21 8746

BCLllA-8584 - GCCCCCGGCCGCGAUGCCCAAC 22 8747

BCLllA-8585 - UGCCCCCGGCCGCGAUGCCCAAC 23 8748

BCLllA-8586 - CUGCCCCCGGCCGCGAUGCCCAAC 24 8749

BCLllA-8587 - AACCUGAUCCCGGAGAAC 18 8750

BCLllA-8588 - CAACCUGAUCCCGGAGAAC 19 8751

BCLllA-5948 - CCAACCUGAUCCCGGAGAAC 20 8752

BCLllA-8589 - CCCAACCUGAUCCCGGAGAAC 21 8753

BCLllA-8590 - CCCCAACCUGAUCCCGGAGAAC 22 8754

BCLllA-8591 - ACCCCAACCUGAUCCCGGAGAAC 23 8755

BCLllA-8592 - GACCCCAACCUGAUCCCGGAGAAC 24 8756

BCLllA-8593 - UCUACUUAGAAAGCGAAC 18 8757

BCLllA-8594 - AUCUACUUAGAAAGCGAAC 19 8758

BCLllA-8595 - AAUCUACUUAGAAAGCGAAC 20 8759

BCLllA-8596 - GAAUCUACUUAGAAAGCGAAC 21 8760

BCLllA-8597 - AGAAUCUACUUAGAAAGCGAAC 22 8761

BCLllA-8598 - AAGAAUCUACUUAGAAAGCGAAC 23 8762

BCLllA-8599 - UAAGAAUCUACUUAGAAAGCGAAC 24 8763

BCLllA-8600 - GAGGCGGCGCGCCACCAC 18 8764

BCLllA-8601 - GGAGGCGGCGCGCCACCAC 19 8765 BCLllA-8602 - UGGAGGCGGCGCGCCACCAC 20 8766

BCLllA-8603 - CUGGAGGCGGCGCGCCACCAC 21 8767

BCLllA-8604 - CCUGGAGGCGGCGCGCCACCAC 22 8768

BCLllA-8605 - GCCUGGAGGCGGCGCGCCACCAC 23 8769

BCLllA-8606 - AGCCUGGAGGCGGCGCGCCACCAC 24 8770

BCLllA-8607 - GUGCACCGGCGCAGCCAC 18 8771

BCLllA-8608 - GGUGCACCGGCGCAGCCAC 19 8772

BCLllA-8609 - UGGUGCACCGGCGCAGCCAC 20 8773

BCLllA-8610 - GUGGUGCACCGGCGCAGCCAC 21 8774

BCLllA-8611 - GGUGGUGCACCGGCGCAGCCAC 22 8775

BCLllA-8612 - UGGUGGUGCACCGGCGCAGCCAC 23 8776

BCLllA-8613 - CUGGUGGUGCACCGGCGCAGCCAC 24 8777

BCLllA-8614 - AG CA AG C UGAAG CG CCAC 18 8778

BCLllA-8615 - CAG CA AG C UGAAG CG CC AC 19 8779

BCLllA-8616 - CCAGCAAGCUGAAGCGCCAC 20 8780

BCLllA-8617 - GCCAGCAAGCUGAAGCGCCAC 21 8781

BCLllA-8618 - GG CCAGCAAG CU G AAG CGCCAC 22 8782

BCLllA-8619 - AGGCCAGCAAGCUGAAGCGCCAC 23 8783

BCLllA-8620 - CAGGCCAGCAAGCUGAAGCGCCAC 24 8784

BCLllA-8621 - GCCGAGGCCGAGGGCCAC 18 8785

BCLllA-8622 - GGCCGAGGCCGAGGGCCAC 19 8786

BCLllA-5951 - UGGCCGAGGCCGAGGGCCAC 20 8787

BCLllA-8623 - CUGGCCGAGGCCGAGGGCCAC 21 8788

BCLllA-8624 - CCUGGCCGAGGCCGAGGGCCAC 22 8789

BCLllA-8625 - ACCUGGCCGAGGCCGAGGGCCAC 23 8790

BCLllA-8626 - CACCUGGCCGAGGCCGAGGGCCAC 24 8791

BCLllA-8627 - CUCGGGGCGCAGCGGCAC 18 8792

BCLllA-8628 - UCUCGGGGCGCAGCGGCAC 19 8793

BCLllA-5953 - AUCUCGGGGCGCAGCGGCAC 20 8794

BCLllA-8629 - GAUCUCGGGGCGCAGCGGCAC 21 8795

BCLllA-8630 - GGAUCUCGGGGCGCAGCGGCAC 22 8796

BCLllA-8631 - GGGAUCUCGGGGCGCAGCGGCAC 23 8797

BCLllA-8632 - AGGGAUCUCGGGGCGCAGCGGCAC 24 8798

BCLllA-8633 - CCACCACCGAGACAUCAC 18 8799

BCLllA-8634 - UCCACCACCGAGACAUCAC 19 8800

BCLllA-8635 - G U CCACCACCG AG ACAU CAC 20 8801

BCLllA-8636 - AGUCCACCACCGAGACAUCAC 21 8802

BCLllA-8637 - UAGUCCACCACCGAGACAUCAC 22 8803

BCLllA-8638 - UUAGUCCACCACCGAGACAUCAC 23 8804

BCLllA-8639 - UUUAGUCCACCACCGAGACAUCAC 24 8805

BCLllA-8640 - GAGGAAGAGGAGGACGAC 18 8806

BCLllA-8641 - GGAGGAAGAGGAGGACGAC 19 8807 BCLllA-3949 - AGGAGGAAGAGGAGGACGAC 20 8808

BCLllA-8642 - GAGGAGGAAGAGGAGGACGAC 21 8809

BCLllA-8643 - CGAGGAGGAAGAGGAGGACGAC 22 8810

BCLllA-8644 - ACGAGGAGGAAGAGGAGGACGAC 23 8811

BCLllA-8645 - GACGAGGAGGAAGAGGAGGACGAC 24 8812

BCLllA-8646 - GUCGUGGGCGUGGGCGAC 18 8813

BCLllA-8647 - GGUCGUGGGCGUGGGCGAC 19 8814

BCLllA-8648 - CGGUCGUGGGCGUGGGCGAC 20 8815

BCLllA-8649 - GCGGUCGUGGGCGUGGGCGAC 21 8816

BCLllA-8650 - CGCGGUCGUGGGCGUGGGCGAC 22 8817

BCLllA-8651 - GCGCGGUCGUGGGCGUGGGCGAC 23 8818

BCLllA-8652 - GGCGCGGUCGUGGGCGUGGGCGAC 24 8819

BCLllA-8653 - AUCCCGGAGAACGGGGAC 18 8820

BCLllA-8654 - GAUCCCGGAGAACGGGGAC 19 8821

BCLllA-8655 - UGAUCCCGGAGAACGGGGAC 20 8822

BCLllA-8656 - CUGAUCCCGGAGAACGGGGAC 21 8823

BCLllA-8657 - CCUGAUCCCGGAGAACGGGGAC 22 8824

BCLllA-8658 - ACCUGAUCCCGGAGAACGGGGAC 23 8825

BCLllA-8659 - AACCUGAUCCCGGAGAACGGGGAC 24 8826

BCLllA-8660 - UGGAGGCGGCGCGCCACC 18 8827

BCLllA-8661 - CUGGAGGCGGCGCGCCACC 19 8828

BCLllA-8662 - CCUGGAGGCGGCGCGCCACC 20 8829

BCLllA-8663 - GCCUGGAGGCGGCGCGCCACC 21 8830

BCLllA-8664 - AGCCUGGAGGCGGCGCGCCACC 22 8831

BCLllA-8665 - GAGCCUGGAGGCGGCGCGCCACC 23 8832

BCLllA-8666 - UGAGCCUGGAGGCGGCGCGCCACC 24 8833

BCLllA-8667 - CCCAUUCGGCGUAGUACC 18 8834

BCLllA-8668 - CCCCAUUCGGCGUAGUACC 19 8835

BCLllA-8669 - CCCCCAUUCGGCGUAGUACC 20 8836

BCLllA-8670 - ACCCCCAUUCGGCGUAGUACC 21 8837

BCLllA-8671 - CACCCCCAUUCGGCGUAGUACC 22 8838

BCLllA-8672 - ACACCCCCAUUCGGCGUAGUACC 23 8839

BCLllA-8673 - CACACCCCCAUUCGGCGUAGUACC 24 8840

BCLllA-8674 - GAGAAAAUUUGAAGCCCC 18 8841

BCLllA-8675 - UGAGAAAAUUUGAAGCCCC 19 8842

BCLllA-8676 - CUGAGAAAAUUUGAAGCCCC 20 8843

BCLllA-8677 - UCUGAGAAAAUUUGAAGCCCC 21 8844

BCLllA-8678 - UUCUGAGAAAAUUUGAAGCCCC 22 8845

BCLllA-8679 - GU UCUGAGAAAAUUUGAAGCCCC 23 8846

BCLllA-8680 - AGUUCUGAGAAAAUUUGAAGCCCC 24 8847

BCLllA-8681 - CGCUUCUCCACACCGCCC 18 8848

BCLllA-8682 - GCGCUUCUCCACACCGCCC 19 8849 BCLllA-5976 - UGCGCUUCUCCACACCGCCC 20 8850

BCLllA-8683 - UUGCGCUUCUCCACACCGCCC 21 8851

BCLllA-8684 - UUUGCGCUUCUCCACACCGCCC 22 8852

BCLllA-8685 - GUUUGCGCUUCUCCACACCGCCC 23 8853

BCLllA-8686 - AGUUUGCGCUUCUCCACACCGCCC 24 8854

BCLllA-8687 - UCUCCACCGCCAGCUCCC 18 8855

BCLllA-8688 - CUCUCCACCGCCAGCUCCC 19 8856

BCLllA-5982 - UCUCUCCACCGCCAGCUCCC 20 8857

BCLllA-8689 - GUCUCUCCACCGCCAGCUCCC 21 8858

BCLllA-8690 - GGUCUCUCCACCGCCAGCUCCC 22 8859

BCLllA-8691 - CGGUCUCUCCACCGCCAGCUCCC 23 8860

BCLllA-8692 - ACGGUCUCUCCACCGCCAGCUCCC 24 8861

BCLllA-8693 - ACGGCUUCGGGCUGAGCC 18 8862

BCLllA-8694 - UACGGCUUCGGGCUGAGCC 19 8863

BCLllA-5986 - CUACGGCUUCGGGCUGAGCC 20 8864

BCLllA-8695 - ACUACGGCUUCGGGCUGAGCC 21 8865

BCLllA-8696 - GACUACGGCUUCGGGCUGAGCC 22 8866

BCLllA-8697 - GGACU ACGGCUUCGGGCUGAGCC 23 8867

BCLllA-8698 - UGGACUACGGCUUCGGGCUGAGCC 24 8868

BCLllA-8699 - GCGCUUCUCCACACCGCC 18 8869

BCLllA-8700 - UGCGCUUCUCCACACCGCC 19 8870

BCLllA-5987 - UUGCGCUUCUCCACACCGCC 20 8871

BCLllA-8701 - UUUGCGCUUCUCCACACCGCC 21 8872

BCLllA-8702 - GUUUGCGCUUCUCCACACCGCC 22 8873

BCLllA-8703 - AGUUUGCGCUUCUCCACACCGCC 23 8874

BCLllA-8704 - GAGUUUGCGCUUCUCCACACCGCC 24 8875

BCLllA-8705 - CCCACCGCAUAGAGCGCC 18 8876

BCLllA-8706 - CCCCACCGCAUAGAGCGCC 19 8877

BCLllA-5988 - CCCCCACCGCAUAGAGCGCC 20 8878

BCLllA-8707 - ACCCCCACCGCAUAGAGCGCC 21 8879

BCLllA-8708 - GACCCCCACCGCAUAGAGCGCC 22 8880

BCLllA-8709 - GGACCCCCACCGCAUAGAGCGCC 23 8881

BCLllA-8710 - UGGACCCCCACCGCAUAGAGCGCC 24 8882

BCLllA-8711 - GGCCACCUGGCCGAGGCC 18 8883

BCLllA-8712 - CGGCCACCUGGCCGAGGCC 19 8884

BCLllA-8713 - GCGGCCACCUGGCCGAGGCC 20 8885

BCLllA-8714 - CGCGGCCACCUGGCCGAGGCC 21 8886

BCLllA-8715 - GCGCGGCCACCUGGCCGAGGCC 22 8887

BCLllA-8716 - AGCGCGGCCACCUGGCCGAGGCC 23 8888

BCLllA-8717 - AAGCGCGGCCACCUGGCCGAGGCC 24 8889

BCLllA-8718 - UCCCCGGGCGAGUCGGCC 18 8890

BCLllA-8719 - CUCCCCGGGCGAGUCGGCC 19 8891 BCLllA-8720 - GCUCCCCGGGCGAGUCGGCC 20 8892

BCLllA-8721 - UGCUCCCCGGGCGAGUCGGCC 21 8893

BCLllA-8722 - CUGCUCCCCGGGCGAGUCGGCC 22 8894

BCLllA-8723 - GCUGCUCCCCGGGCGAGUCGGCC 23 8895

BCLllA-8724 - GGCUGCUCCCCGGGCGAGUCGGCC 24 8896

BCLllA-8725 - ACGACCCCAACCUGAUCC 18 8897

BCLllA-8726 - AACGACCCCAACCUGAUCC 19 8898

BCLllA-6004 - GAACGACCCCAACCUGAUCC 20 8899

BCLllA-8727 - AGAACGACCCCAACCUGAUCC 21 8900

BCLllA-8728 - GAGAACGACCCCAACCUGAUCC 22 8901

BCLllA-8729 - CGAGAACGACCCCAACCUGAUCC 23 8902

BCLllA-8730 - GCGAGAACGACCCCAACCUGAUCC 24 8903

BCLllA-8731 - UCCUCGUCGGAGCACUCC 18 8904

BCLllA-8732 - CUCCUCGUCGGAGCACUCC 19 8905

BCLllA-8733 - CCUCCUCGUCGGAGCACUCC 20 8906

BCLllA-8734 - GCCUCCUCGUCGGAGCACUCC 21 8907

BCLllA-8735 - UGCCUCCUCGUCGGAGCACUCC 22 8908

BCLllA-8736 - UUGCCUCCUCGUCGGAGCACUCC 23 8909

BCLllA-8737 - UUUGCCUCCUCGUCGGAGCACUCC 24 8910

BCLllA-8738 - CUCUCCACCGCCAGCUCC 18 8911

BCLllA-8739 - UCUCUCCACCGCCAGCUCC 19 8912

BCLllA-8740 - GUCUCUCCACCGCCAGCUCC 20 8913

BCLllA-8741 - GGUCUCUCCACCGCCAGCUCC 21 8914

BCLllA-8742 - CGGUCUCUCCACCGCCAGCUCC 22 8915

BCLllA-8743 - ACGGUCUCUCCACCGCCAGCUCC 23 8916

BCLllA-8744 - GACGGUCUCUCCACCGCCAGCUCC 24 8917

BCLllA-8745 - AAUGGCCGCGGCUGCUCC 18 8918

BCLllA-8746 - UAAUGGCCGCGGCUGCUCC 19 8919

BCLllA-8747 - UUAAUGGCCGCGGCUGCUCC 20 8920

BCLllA-8748 - GUUAAUGGCCGCGGCUGCUCC 21 8921

BCLllA-8749 - UGUUAAUGGCCGCGGCUGCUCC 22 8922

BCLllA-8750 - CUGUUAAUGGCCGCGGCUGCUCC 23 8923

BCLllA-8751 - ACUGUUAAUGGCCGCGGCUGCUCC 24 8924

BCLllA-8752 - CUUCCCAGCCACCUCUCC 18 8925

BCLllA-8753 - CCUUCCCAGCCACCUCUCC 19 8926

BCLllA-8754 - UCCUUCCCAGCCACCUCUCC 20 8927

BCLllA-8755 - GUCCUUCCCAGCCACCUCUCC 21 8928

BCLllA-8756 - UGUCCUUCCCAGCCACCUCUCC 22 8929

BCLllA-8757 - AUGUCCUUCCCAGCCACCUCUCC 23 8930

BCLllA-8758 - AAUGUCCUUCCCAGCCACCUCUCC 24 8931

BCLllA-8759 - UCUCUAAGCGCAUCAAGC 18 8932

BCLllA-8760 - UUCUCUAAGCGCAUCAAGC 19 8933 BCLllA-8761 - CUUCUCUAAGCGCAUCAAGC 20 8934

BCLllA-8762 - CCUUCUCUAAGCGCAUCAAGC 21 8935

BCLllA-8763 - CCCUUCUCUAAGCGCAUCAAGC 22 8936

BCLllA-8764 - CCCCUUCUCUAAGCGCAUCAAGC 23 8937

BCLllA-8765 - GCCCCUUCUCUAAGCGCAUCAAGC 24 8938

BCLllA-8766 - CAGUUUUCGGAUGGAAGC 18 8939

BCLllA-8767 - GCAGUUUUCGGAUGGAAGC 19 8940

BCLllA-8768 - GGCAGUUUUCGGAUGGAAGC 20 8941

BCLllA-8769 - UGGCAGUUUUCGGAUGGAAGC 21 8942

BCLllA-8770 - GUGGCAGUUUUCGGAUGGAAGC 22 8943

BCLllA-8771 - UGUGGCAGUUUUCGGAUGGAAGC 23 8944

BCLllA-8772 - GUGUGGCAGUUUUCGGAUGGAAGC 24 8945

BCLllA-8773 - G U G G C C A AG UUCAAGAGC 18 8946

BCLllA-8774 - GGUGGCCAAGUUCAAGAGC 19 8947

BCLllA-8775 - UGGUGGCCAAGUUCAAGAGC 20 8948

BCLllA-8776 - G UGGUGGCCAAG U U CAAG AG C 21 8949

BCLllA-8777 - CGUGGUGGCCAAGUUCAAGAGC 22 8950

BCLllA-8778 - CCGUGGUGGCCAAGUUCAAGAGC 23 8951

BCLllA-8779 - UCCGUGGUGGCCAAGUUCAAGAGC 24 8952

BCLllA-8780 - GAGGAGCUGACGGAGAGC 18 8953

BCLllA-8781 - GGAGGAGCUGACGGAGAGC 19 8954

BCLllA-8782 - AGGAGGAGCUGACGGAGAGC 20 8955

BCLllA-8783 - GAGGAGGAGCUGACGGAGAGC 21 8956

BCLllA-8784 - GGAGGAGGAGCUGACGGAGAGC 22 8957

BCLllA-8785 - AGGAGGAGGAGCUGACGGAGAGC 23 8958

BCLllA-8786 - GAGGAGGAGGAGCUGACGGAGAGC 24 8959

BCLllA-8787 - UACGGCUUCGGGCUGAGC 18 8960

BCLllA-8788 - CUACGGCUUCGGGCUGAGC 19 8961

BCLllA-8789 - ACUACGGCUUCGGGCUGAGC 20 8962

BCLllA-8790 - GACUACGGCUUCGGGCUGAGC 21 8963

BCLllA-8791 - GGACUACGGCUUCGGGCUGAGC 22 8964

BCLllA-8792 - UGGACUACGGCUUCGGGCUGAGC 23 8965

BCLllA-8793 - GUGGACUACGGCUUCGGGCUGAGC 24 8966

BCLllA-8794 - UGCGCUUCUCCACACCGC 18 8967

BCLllA-8795 - UUGCGCUUCUCCACACCGC 19 8968

BCLllA-8796 - UUUGCGCUUCUCCACACCGC 20 8969

BCLllA-8797 - GUUUGCGCUUCUCCACACCGC 21 8970

BCLllA-8798 - AGUUUGCGCUUCUCCACACCGC 22 8971

BCLllA-8799 - GAGUUUGCGCUUCUCCACACCGC 23 8972

BCLllA-8800 - GGAGUUUGCGCUUCUCCACACCGC 24 8973

BCLllA-8801 - CCCCACCGCAUAGAGCGC 18 8974

BCLllA-8802 - CCCCCACCGCAUAGAGCGC 19 8975 BCLllA-8803 - ACCCCCACCGCAUAGAGCGC 20 8976

BCLllA-8804 - GACCCCCACCGCAUAGAGCGC 21 8977

BCLllA-8805 - GGACCCCCACCGCAUAGAGCGC 22 8978

BCLllA-8806 - UGGACCCCCACCGCAUAGAGCGC 23 8979

BCLllA-8807 - UUGGACCCCCACCGCAUAGAGCGC 24 8980

BCLllA-8808 - AUCUCGGGGCGCAGCGGC 18 8981

BCLllA-8809 - GAUCUCGGGGCGCAGCGGC 19 8982

BCLllA-8810 - GGAUCUCGGGGCGCAGCGGC 20 8983

BCLllA-8811 - GGGAUCUCGGGGCGCAGCGGC 21 8984

BCLllA-8812 - AGGGAUCUCGGGGCGCAGCGGC 22 8985

BCLllA-8813 - GAGGGAUCUCGGGGCGCAGCGGC 23 8986

BCLllA-8814 - GGAGGGAUCUCGGGGCGCAGCGGC 24 8987

BCLllA-8815 - CGGCGCAGCCACACGGGC 18 8988

BCLllA-8816 - CCGGCGCAGCCACACGGGC 19 8989

BCLllA-3804 - ACCGGCGCAGCCACACGGGC 20 8990

BCLllA-8817 - CACCGGCGCAGCCACACGGGC 21 8991

BCLllA-8818 - GCACCGGCGCAGCCACACGGGC 22 8992

BCLllA-8819 - UGCACCGGCGCAGCCACACGGGC 23 8993

BCLllA-8820 - GUGCACCGGCGCAGCCACACGGGC 24 8994

BCLllA-8821 - CAUAUUAGUGGUCCGGGC 18 8995

BCLllA-8822 - CCAUAUUAGUGGUCCGGGC 19 8996

BCLllA-8823 - CCCAUAUUAGUGGUCCGGGC 20 8997

BCLllA-8824 - CCCCAUAUUAGUGGUCCGGGC 21 8998

BCLllA-8825 - GCCCCAUAUUAGUGGUCCGGGC 22 8999

BCLllA-8826 - CGCCCCAUAUUAGUGGUCCGGGC 23 9000

BCLllA-8827 - ACGCCCCAUAUUAGUGGUCCGGGC 24 9001

BCLllA-8828 - UUCCACCAGGUCCUGGGC 18 9002

BCLllA-8829 - CUUCCACCAGGUCCUGGGC 19 9003

BCLllA-8830 - CCUUCCACCAGGUCCUGGGC 20 9004

BCLllA-8831 - GCCUUCCACCAGGUCCUGGGC 21 9005

BCLllA-8832 - GGCCUUCCACCAGGUCCUGGGC 22 9006

BCLllA-8833 - AGGCCUUCCACCAGGUCCUGGGC 23 9007

BCLllA-8834 - GAGGCCUUCCACCAGGUCCUGGGC 24 9008

BCLllA-8835 - CGGGGCGCGGUCGUGGGC 18 9009

BCLllA-8836 - GCGGGGCGCGGUCGUGGGC 19 9010

BCLllA-8837 - CGCGGGGCGCGGUCGUGGGC 20 9011

BCLllA-8838 - UCGCGGGGCGCGGUCGUGGGC 21 9012

BCLllA-8839 - CUCGCGGGGCGCGGUCGUGGGC 22 9013

BCLllA-8840 - GCUCGCGGGGCGCGGUCGUGGGC 23 9014

BCLllA-8841 - AGCUCGCGGGGCGCGGUCGUGGGC 24 9015

BCLllA-8842 - GAGACUUAGAGAGCUGGC 18 9016

BCLllA-8843 - GGAGACUUAGAGAGCUGGC 19 9017 BCLllA-6037 - AGGAGACUUAGAGAGCUGGC 20 9018

BCLllA-8844 - UAGGAGACUUAGAGAGCUGGC 21 9019

BCLllA-8845 - CUAGGAGACUUAGAGAGCUGGC 22 9020

BCLllA-8846 - UCUAGGAGACUUAGAGAGCUGGC 23 9021

BCLllA-8847 - CUCUAGGAGACUUAGAGAGCUGGC 24 9022

BCLllA-8848 - GAGCUGGACGGAGGGAUC 18 9023

BCLllA-8849 - GGAGCUGGACGGAGGGAUC 19 9024

BCLllA-8850 - GGGAGCUGGACGGAGGGAUC 20 9025

BCLllA-8851 - GGGGAGCUGGACGGAGGGAUC 21 9026

BCLllA-8852 - CGGGGAGCUGGACGGAGGGAUC 22 9027

BCLllA-8853 - CCGGGGAGCUGGACGGAGGGAUC 23 9028

BCLllA-8854 - CCCGGGGAGCUGGACGGAGGGAUC 24 9029

BCLllA-8855 - AACGACCCCAACCUGAUC 18 9030

BCLllA-8856 - GAACGACCCCAACCUGAUC 19 9031

BCLllA-8857 - AGAACGACCCCAACCUGAUC 20 9032

BCLllA-8858 - GAGAACGACCCCAACCUGAUC 21 9033

BCLllA-8859 - CGAGAACGACCCCAACCUGAUC 22 9034

BCLllA-8860 - GCGAGAACGACCCCAACCUGAUC 23 9035

BCLllA-8861 - AGCGAGAACGACCCCAACCUGAUC 24 9036

BCLllA-8862 - AAUACCAGGAUCAGUAUC 18 9037

BCLllA-8863 - GAAUACCAGGAUCAGUAUC 19 9038

BCLllA-8864 - AGAAUACCAGGAUCAGUAUC 20 9039

BCLllA-8865 - AAGAAUACCAGGAUCAGUAUC 21 9040

BCLllA-8866 - UAAGAAUACCAGGAUCAGUAUC 22 9041

BCLllA-8867 - CUAAGAAUACCAGGAUCAGUAUC 23 9042

BCLllA-8868 - GCUAAGAAUACCAGGAUCAGUAUC 24 9043

BCLllA-8869 - CCCGGGCGAGUCGGCCUC 18 9044

BCLllA-8870 - CCCCGGGCGAGUCGGCCUC 19 9045

BCLllA-6047 - UCCCCGGGCGAGUCGGCCUC 20 9046

BCLllA-8871 - CUCCCCGGGCGAGUCGGCCUC 21 9047

BCLllA-8872 - GCUCCCCGGGCGAGUCGGCCUC 22 9048

BCLllA-8873 - UGCUCCCCGGGCGAGUCGGCCUC 23 9049

BCLllA-8874 - CUGCUCCCCGGGCGAGUCGGCCUC 24 9050

BCLllA-8875 - UCUAAGCGCAUCAAGCUC 18 9051

BCLllA-8876 - CUCUAAGCGCAUCAAGCUC 19 9052

BCLllA-8877 - UCUCUAAGCGCAUCAAGCUC 20 9053

BCLllA-8878 - UUCUCUAAGCGCAUCAAGCUC 21 9054

BCLllA-8879 - CUUCUCUAAGCGCAUCAAGCUC 22 9055

BCLllA-8880 - CCUUCUCUAAGCGCAUCAAGCUC 23 9056

BCLllA-8881 - CCCUUCUCUAAGCGCAUCAAGCUC 24 9057

BCLllA-8882 - GUUUUCGGAUGGAAGCUC 18 9058

BCLllA-8883 - AGUUUUCGGAUGGAAGCUC 19 9059 BCLllA-8884 - CAGUUUUCGGAUGGAAGCUC 20 9060

BCLllA-8885 - GCAGUUUUCGGAUGGAAGCUC 21 9061

BCLllA-8886 - GGCAGUUUUCGGAUGGAAGCUC 22 9062

BCLllA-8887 - UGGCAGUUUUCGGAUGGAAGCUC 23 9063

BCLllA-8888 - GUGGCAGUUUUCGGAUGGAAGCUC 24 9064

BCLllA-8889 - CC ACC ACG AG A ACAG C U C 18 9065

BCLllA-8890 - GCCACCACGAGAACAGCUC 19 9066

BCLllA-8891 - CGCCACCACGAGAACAGCUC 20 9067

BCLllA-8892 - GCGCCACCACGAGAACAGCUC 21 9068

BCLllA-8893 - CGCGCCACCACGAGAACAGCUC 22 9069

BCLllA-8894 - GCGCGCCACCACGAGAACAGCUC 23 9070

BCLllA-8895 - GGCGCGCCACCACGAGAACAGCUC 24 9071

BCLllA-8896 - UCCCGCCAUGGAUUUCUC 18 9072

BCLllA-8897 - CUCCCGCCAUGGAUUUCUC 19 9073

BCLllA-8898 - CCUCCCGCCAUGGAUUUCUC 20 9074

BCLllA-8899 - GCCUCCCGCCAUGGAUUUCUC 21 9075

BCLllA-8900 - AGCCUCCCGCCAUGGAUUUCUC 22 9076

BCLllA-8901 - GAGCCUCCCGCCAUGGAUUUCUC 23 9077

BCLllA-8902 - GGAGCCUCCCGCCAUGGAUUUCUC 24 9078

BCLllA-8903 - GAGGCCUUCCACCAGGUC 18 9079

BCLllA-8904 - CGAGGCCUUCCACCAGGUC 19 9080

BCLllA-8905 - GCGAGGCCUUCCACCAGGUC 20 9081

BCLllA-8906 - AGCGAGGCCUUCCACCAGGUC 21 9082

BCLllA-8907 - CAGCGAGGCCUUCCACCAGGUC 22 9083

BCLllA-8908 - UCAGCGAGGCCUUCCACCAGGUC 23 9084

BCLllA-8909 - UUCAGCGAGGCCUUCCACCAGGUC 24 9085

BCLllA-8910 - AGCUCGCGGGGCGCGGUC 18 9086

BCLllA-8911 - CAGCUCGCGGGGCGCGGUC 19 9087

BCLllA-8912 - ACAGCUCGCGGGGCGCGGUC 20 9088

BCLllA-8913 - AACAGCUCGCGGGGCGCGGUC 21 9089

BCLllA-8914 - GAACAGCUCGCGGGGCGCGGUC 22 9090

BCLllA-8915 - AGAA CAGCUCGCGGGGCGCGGUC 23 9091

BCLllA-8916 - GAGAACAGCUCGCGGGGCGCGGUC 24 9092

BCLllA-8917 - UACUGUGGGAAAGUCUUC 18 9093

BCLllA-8918 - GUACUGUGGGAAAGUCUUC 19 9094

BCLllA-8919 - AGUACUGUGGGAAAGUCUUC 20 9095

BCLllA-8920 - GAGUACUGUGGGAAAGUCUUC 21 9096

BCLllA-8921 - UGAGUACUGUGGGAAAGUCUUC 22 9097

BCLllA-8922 - GUGAGUACUGUGGGAAAGUCUUC 23 9098

BCLllA-8923 - UGUGAGUACUGUGGGAAAGUCUUC 24 9099

BCLllA-8924 - UCCGUGGUGGCCAAGUUC 18 9100

BCLllA-8925 - GUCCGUGGUGGCCAAGUUC 19 9101 BCLllA-8926 - AGUCCGUGGUGGCCAAGUUC 20 9102

BCLllA-8927 - AAGUCCGUGGUGGCCAAGUUC 21 9103

BCLllA-8928 - CAAGUCCGUGGUGGCCAAGUUC 22 9104

BCLllA-8929 - UCAAGUCCGUGGUGGCCAAGUUC 23 9105

BCLllA-8930 - CUCAAGUCCGUGGUGGCCAAGUUC 24 9106

BCLllA-6826 - AUUAUUUUGCAGGUAAAG 18 9107

BCLllA-6827 - UAUUAUUUUGCAGGUAAAG 19 9108

BCLllA-6828 - GUAUUAUUUUGCAGGUAAAG 20 9109

BCLllA-8931 - U GCACCCAGG CCAG CAAG 18 9110

BCLllA-8932 - GUGCACCCAGGCCAGCAAG 19 9111

BCLllA-8933 - CGUGCACCCAGGCCAGCAAG 20 9112

BCLllA-8934 - GCGUGCACCCAGGCCAGCAAG 21 9113

BCLllA-8935 - CGCGUGCACCCAGGCCAGCAAG 22 9114

BCLllA-8936 - ACGCGUGCACCCAGGCCAGCAAG 23 9115

BCLllA-8937 - CACG CG UG CACCCAGG CCAGCAAG 24 9116

BCLllA-8938 - ACGAGGAAGAGGAAGAAG 18 9117

BCLllA-8939 - GACGAGGAAGAGGAAGAAG 19 9118

BCLllA-3449 - CGACGAGGAAGAGGAAGAAG 20 9119

BCLllA-8940 - ACGACGAGGAAGAGGAAGAAG 21 9120

BCLllA-8941 - GACGACGAGGAAGAGGAAGAAG 22 9121

BCLllA-8942 - GGACGACGAGGAAGAGGAAGAAG 23 9122

BCLllA-8943 - AGGACGACGAGGAAGAGGAAGAAG 24 9123

BCLllA-8944 - ACGACGAGGAAGAGGAAG 18 9124

BCLllA-8945 - GACGACGAGGAAGAGGAAG 19 9125

BCLllA-3959 - GGACGACGAGGAAGAGGAAG 20 9126

BCLllA-8946 - AGGACGACGAGGAAGAGGAAG 21 9127

BCLllA-8947 - GAGGACGACGAGGAAGAGGAAG 22 9128

BCLllA-8948 - GGAGGACGACGAGGAAGAGGAAG 23 9129

BCLllA-8949 - AGGAGGACGACGAGGAAGAGGAAG 24 9130

BCLllA-8950 - AGGAGGACGACGAGGAAG 18 9131

BCLllA-8951 - GAGGAGGACGACGAGGAAG 19 9132

BCLllA-3448 - AGAGGAGGACGACGAGGAAG 20 9133

BCLllA-8952 - AAGAGGAGGACGACGAGGAAG 21 9134

BCLllA-8953 - GAAGAGGAGGACGACGAGGAAG 22 9135

BCLllA-8954 - GGAAGAGGAGGACGACGAGGAAG 23 9136

BCLllA-8955 - AGGAAGAGGAGGACGACGAGGAAG 24 9137

BCLllA-8956 - AGGAAGAAGAGGAGGAAG 18 9138

BCLllA-8957 - GAGGAAGAAGAGGAGGAAG 19 9139

BCLllA-3453 - AGAGGAAGAAGAGGAGGAAG 20 9140

BCLllA-8958 - AAGAGGAAGAAGAGGAGGAAG 21 9141

BCLllA-8959 - GAAGAGGAAGAAGAGGAGGAAG 22 9142

BCLllA-8960 - GGAAGAGGAAGAAGAGGAGGAAG 23 9143 BCLllA-8961 - AGGAAGAGGAAGAAGAGGAGGAAG 24 9144

BCLllA-8962 - ACGGGGACGAGGAGGAAG 18 9145

BCLllA-8963 - AACGGGGACGAGGAGGAAG 19 9146

BCLllA-3441 - GAACGGGGACGAGGAGGAAG 20 9147

BCLllA-8964 - AGAACGGGGACGAGGAGGAAG 21 9148

BCLllA-8965 - GAGAACGGGGACGAGGAGGAAG 22 9149

BCLllA-8966 - GGAGAACGGGGACGAGGAGGAAG 23 9150

BCLllA-8967 - CGGAGAACGGGGACGAGGAGGAAG 24 9151

BCLllA-8968 - GCGCAGCGGCACGGGAAG 18 9152

BCLllA-8969 - GGCGCAGCGGCACGGGAAG 19 9153

BCLllA-3376 - GGGCGCAGCGGCACGGGAAG 20 9154

BCLllA-8970 - GGGGCGCAGCGGCACGGGAAG 21 9155

BCLllA-8971 - CGGGGCGCAGCGGCACGGGAAG 22 9156

BCLllA-8972 - UCGGGGCGCAGCGGCACGGGAAG 23 9157

BCLllA-8973 - CUCGGGGCGCAGCGGCACGGGAAG 24 9158

BCLllA-8974 - AGGCUUCCGGCCUGGCAG 18 9159

BCLllA-8975 - GAGGCUUCCGGCCUGGCAG 19 9160

BCLllA-8976 - AGAGGCUUCCGGCCUGGCAG 20 9161

BCLllA-8977 - GAGAGGCUUCCGGCCUGGCAG 21 9162

BCLllA-8978 - AGAGAGGCUUCCGGCCUGGCAG 22 9163

BCLllA-8979 - GAGAGAGGCUUCCGGCCUGGCAG 23 9164

BCLllA-8980 - CGAGAGAGGCUUCCGGCCUGGCAG 24 9165

BCLllA-8981 - GAGGAAGAGGAAGAAGAG 18 9166

BCLllA-8982 - CGAGGAAGAGGAAGAAGAG 19 9167

BCLllA-3948 - ACGAGGAAGAGGAAGAAGAG 20 9168

BCLllA-8983 - GACGAGGAAGAGGAAGAAGAG 21 9169

BCLllA-8984 - CGACGAGGAAGAGGAAGAAGAG 22 9170

BCLllA-8985 - ACGACGAGGAAGAGGAAGAAGAG 23 9171

BCLllA-8986 - GACGACGAGGAAGAGGAAGAAGAG 24 9172

BCLllA-8987 - GAAGAAGAGGAGGAAGAG 18 9173

BCLllA-8988 - GGAAGAAGAGGAGGAAGAG 19 9174

BCLllA-3961 - AGGAAGAAGAGGAGGAAGAG 20 9175

BCLllA-8989 - GAGGAAGAAGAGGAGGAAGAG 21 9176

BCLllA-8990 - AGAGGAAGAAGAGGAGGAAGAG 22 9177

BCLllA-8991 - AAGAGGAAGAAGAGGAGGAAGAG 23 9178

BCLllA-8992 - GAAGAGGAAGAAGAGGAGGAAGAG 24 9179

BCLllA-8993 - GGGGACGAGGAGGAAGAG 18 9180

BCLllA-8994 - CGGGGACGAGGAGGAAGAG 19 9181

BCLllA-3945 - ACGGGGACGAGGAGGAAGAG 20 9182

BCLllA-8995 - AACGGGGACGAGGAGGAAGAG 21 9183

BCLllA-8996 - GAACGGGGACGAGGAGGAAGAG 22 9184

BCLllA-8997 - AGAACGGGGACGAGGAGGAAGAG 23 9185 BCLllA-8998 - GAGAACGGGGACGAGGAGGAAGAG 24 9186

BCLllA-8999 - CCGGAGAACGGGGACGAG 18 9187

BCLllA-9000 - CCCGGAGAACGGGGACGAG 19 9188

BCLllA-9001 - UCCCGGAGAACGGGGACGAG 20 9189

BCLllA-9002 - AUCCCGGAGAACGGGGACGAG 21 9190

BCLllA-9003 - GAUCCCGGAGAACGGGGACGAG 22 9191

BCLllA-9004 - UGAUCCCGGAGAACGGGGACGAG 23 9192

BCLllA-9005 - CUGAUCCCGGAGAACGGGGACGAG 24 9193

BCLllA-9006 - GACUCGGUGGCCGGCGAG 18 9194

BCLllA-9007 - AGACUCGGUGGCCGGCGAG 19 9195

BCLllA-9008 - AAGACUCGGUGGCCGGCGAG 20 9196

BCLllA-9009 - GAAGACUCGGUGGCCGGCGAG 21 9197

BCLllA-9010 - CGAAGACUCGGUGGCCGGCGAG 22 9198

BCLllA-9011 - ACGAAGACUCGGUGGCCGGCGAG 23 9199

BCLllA-9012 - GACGAAGACUCGGUGGCCGGCGAG 24 9200

BCLllA-9013 - AAGCGCAUCAAGCUCGAG 18 9201

BCLllA-9014 - UAAGCGCAUCAAGCUCGAG 19 9202

BCLllA-9015 - CUAAGCGCAUCAAGCUCGAG 20 9203

BCLllA-9016 - UCU AAGCGCAUCAAGCUCGAG 21 9204

BCLllA-9017 - CUCUAAGCGCAUCAAGCUCGAG 22 9205

BCLllA-9018 - UCUCUAAGCGCAUCAAGCUCGAG 23 9206

BCLllA-9019 - UUCUCUAAGCGCAUCAAGCUCGAG 24 9207

BCLllA-9020 - GAAGAGGAGGAAGAGGAG 18 9208

BCLllA-9021 - AGAAGAGGAGGAAGAGGAG 19 9209

BCLllA-3964 - AAGAAGAGGAGGAAGAGGAG 20 9210

BCLllA-9022 - GAAGAAGAGGAGGAAGAGGAG 21 9211

BCLllA-9023 - GGAAGAAGAGGAGGAAGAGGAG 22 9212

BCLllA-9024 - AGGAAGAAGAGGAGGAAGAGGAG 23 9213

BCLllA-9025 - GAGGAAGAAGAGGAGGAAGAGGAG 24 9214

BCLllA-9026 - GAGGAGGAAGAGGAGGAG 18 9215

BCLllA-9027 - AGAGGAGGAAGAGGAGGAG 19 9216

BCLllA-3965 - AAGAGGAGGAAGAGGAGGAG 20 9217

BCLllA-9028 - GAAGAGGAGGAAGAGGAGGAG 21 9218

BCLllA-9029 - AGAAGAGGAGGAAGAGGAGGAG 22 9219

BCLllA-9030 - AAGAAGAGGAGGAAGAGGAGGAG 23 9220

BCLllA-9031 - GAAGAAGAGGAGGAAGAGGAGGAG 24 9221

BCLllA-9032 - UCCACACCGCCCGGGGAG 18 9222

BCLllA-9033 - CUCCACACCGCCCGGGGAG 19 9223

BCLllA-9034 - UCUCCACACCGCCCGGGGAG 20 9224

BCLllA-9035 - UUCUCCACACCGCCCGGGGAG 21 9225

BCLllA-9036 - CUUCUCCACACCGCCCGGGGAG 22 9226

BCLllA-9037 - GCUUCUCCACACCGCCCGGGGAG 23 9227 BCLllA-9038 - CGCUUCUCCACACCGCCCGGGGAG 24 9228

BCLllA-9039 - GCCGCGAUGCCCAACACG 18 9229

BCLllA-9040 - GGCCGCGAUGCCCAACACG 19 9230

BCLllA-9041 - CGGCCGCGAUGCCCAACACG 20 9231

BCLllA-9042 - CCGGCCGCGAUGCCCAACACG 21 9232

BCLllA-9043 - CCCGGCCGCGAUGCCCAACACG 22 9233

BCLllA-9044 - CCCCGGCCGCGAUGCCCAACACG 23 9234

BCLllA-9045 - CCCCCGGCCGCGAUGCCCAACACG 24 9235

BCLllA-9046 - AGGAAGAGGAGGACGACG 18 9236

BCLllA-9047 - GAGGAAGAGGAGGACGACG 19 9237

BCLllA-3450 - GGAGGAAGAGGAGGACGACG 20 9238

BCLllA-9048 - AGGAGGAAGAGGAGGACGACG 21 9239

BCLllA-9049 - GAGGAGGAAGAGGAGGACGACG 22 9240

BCLllA-9050 - CGAGGAGGAAGAGGAGGACGACG 23 9241

BCLllA-9051 - ACGAGGAGGAAGAGGAGGACGACG 24 9242

BCLllA-9052 - AGGAGGAAGAGGAGGACG 18 9243

BCLllA-9053 - GAGGAGGAAGAGGAGGACG 19 9244

BCLllA-3953 - CGAGGAGGAAGAGGAGGACG 20 9245

BCLllA-9054 - ACGAGGAGGAAGAGGAGGACG 21 9246

BCLllA-9055 - GACGAGGAGGAAGAGGAGGACG 22 9247

BCLllA-9056 - GGACGAGGAGGAAGAGGAGGACG 23 9248

BCLllA-9057 - GGGACGAGGAGGAAGAGGAGGACG 24 9249

BCLllA-9058 - UCCCGGAGAACGGGGACG 18 9250

BCLllA-9059 - AUCCCGGAGAACGGGGACG 19 9251

BCLllA-6081 - GAUCCCGGAGAACGGGGACG 20 9252

BCLllA-9060 - UGAUCCCGGAGAACGGGGACG 21 9253

BCLllA-9061 - CUGAUCCCGGAGAACGGGGACG 22 9254

BCLllA-9062 - CCUGAUCCCGGAGAACGGGGACG 23 9255

BCLllA-9063 - ACCUGAUCCCGGAGAACGGGGACG 24 9256

BCLllA-9064 - CGCCCGGGGAGCUGGACG 18 9257

BCLllA-9065 - CCGCCCGGGGAGCUGGACG 19 9258

BCLllA-9066 - ACCGCCCGGGGAGCUGGACG 20 9259

BCLllA-9067 - CACCGCCCGGGGAGCUGGACG 21 9260

BCLllA-9068 - ACACCGCCCGGGGAGCUGGACG 22 9261

BCLllA-9069 - CACACCGCCCGGGGAGCUGGACG 23 9262

BCLllA-9070 - CCACACCGCCCGGGGAGCUGGACG 24 9263

BCLllA-9071 - GAGGAGGAGGAGCUGACG 18 9264

BCLllA-9072 - GGAGGAGGAGGAGCUGACG 19 9265

BCLllA-9073 - AGGAGGAGGAGGAGCUGACG 20 9266

BCLllA-9074 - GAGGAGGAGGAGGAGCUGACG 21 9267

BCLllA-9075 - AGAGGAGGAGGAGGAGCUGACG 22 9268

BCLllA-9076 - AAGAGGAGGAGGAGGAGCUGACG 23 9269 BCLllA-9077 - GAAGAGGAGGAGGAGGAGCUGACG 24 9270

BCLllA-9078 - GCUUCUCCACACCGCCCG 18 9271

BCLllA-9079 - CGCUUCUCCACACCGCCCG 19 9272

BCLllA-6087 - GCGCUUCUCCACACCGCCCG 20 9273

BCLllA-9080 - UGCGCUUCUCCACACCGCCCG 21 9274

BCLllA-9081 - UUGCGCUUCUCCACACCGCCCG 22 9275

BCLllA-9082 - UUUGCGCUUCUCCACACCGCCCG 23 9276

BCLllA-9083 - GUUUGCGCUUCUCCACACCGCCCG 24 9277

BCLllA-9084 - GACCCCAACCUGAUCCCG 18 9278

BCLllA-9085 - CGACCCCAACCUGAUCCCG 19 9279

BCLllA-9086 - ACGACCCCAACCUGAUCCCG 20 9280

BCLllA-9087 - AACGACCCCAACCUGAUCCCG 21 9281

BCLllA-9088 - GAACGACCCCAACCUGAUCCCG 22 9282

BCLllA-9089 - AGAACGACCCCAACCUGAUCCCG 23 9283

BCLllA-9090 - GAGAACGACCCCAACCUGAUCCCG 24 9284

BCLllA-9091 - CGGUCGUGGGCGUGGGCG 18 9285

BCLllA-9092 - GCGGUCGUGGGCGUGGGCG 19 9286

BCLllA-9093 - CGCGGUCGUGGGCGUGGGCG 20 9287

BCLllA-9094 - GCGCGGUCGUGGGCGUGGGCG 21 9288

BCLllA-9095 - GGCGCGGUCGUGGGCGUGGGCG 22 9289

BCLllA-9096 - GGGCGCGGUCGUGGGCGUGGGCG 23 9290

BCLllA-9097 - GGGGCGCGGUCGUGGGCGUGGGCG 24 9291

BCLllA-9098 - GCCACAGGGACACUUGCG 18 9292

BCLllA-9099 - GGCCACAGGGACACUUGCG 19 9293

BCLllA-9100 - GGGCCACAGGGACACUUGCG 20 9294

BCLllA-9101 - AGGGCCACAGGGACACUUGCG 21 9295

BCLllA-9102 - GAGGGCCACAGGGACACUUGCG 22 9296

BCLllA-9103 - CGAGGGCCACAGGGACACUUGCG 23 9297

BCLllA-9104 - CCGAGGGCCACAGGGACACUUGCG 24 9298

BCLllA-9105 - CCGGGCGAGUCGGCCUCG 18 9299

BCLllA-9106 - CCCGGGCGAGUCGGCCUCG 19 9300

BCLllA-6106 - CCCCGGGCGAGUCGGCCUCG 20 9301

BCLllA-9107 - UCCCCGGGCGAGUCGGCCUCG 21 9302

BCLllA-9108 - CUCCCCGGGCGAGUCGGCCUCG 22 9303

BCLllA-9109 - GCUCCCCGGGCGAGUCGGCCUCG 23 9304

BCLllA-9110 - UGCUCCCCGGGCGAGUCGGCCUCG 24 9305

BCLllA-9111 - UCGUCGGAGCACUCCUCG 18 9306

BCLllA-9112 - CUCGUCGGAGCACUCCUCG 19 9307

BCLllA-9113 - CCUCGUCGGAGCACUCCUCG 20 9308

BCLllA-9114 - UCCUCGUCGGAGCACUCCUCG 21 9309

BCLllA-9115 - CUCCUCGUCGGAGCACUCCUCG 22 9310

BCLllA-9116 - CCUCCUCGUCGGAGCACUCCUCG 23 9311 BCLllA-9117 - GCCUCCUCGUCGGAGCACUCCUCG 24 9312

BCLllA-9118 - UCGCCUUUUGCCUCCUCG 18 9313

BCLllA-9119 - AUCGCCUUUUGCCUCCUCG 19 9314

BCLllA-9120 - AAUCGCCUUUUGCCUCCUCG 20 9315

BCLllA-9121 - CAAUCGCCUUUUGCCUCCUCG 21 9316

BCLllA-9122 - ACAAUCGCCUUUUGCCUCCUCG 22 9317

BCLllA-9123 - GACAAUCGCCUUUUGCCUCCUCG 23 9318

BCLllA-9124 - AGACAAUCGCCUUUUGCCUCCUCG 24 9319

BCLllA-9125 - CACCACG AG AACAG CU CG 18 9320

BCLllA-9126 - CCACCACGAGAACAGCUCG 19 9321

BCLllA-6107 - GCCACCACGAGAACAGCUCG 20 9322

BCLllA-9127 - CGCCACCACGAGAACAGCUCG 21 9323

BCLllA-9128 - GCGCCACCACGAGAACAGCUCG 22 9324

BCLllA-9129 - CGCGCCACCACGAGAACAGCUCG 23 9325

BCLllA-9130 - GCGCGCCACCACGAGAACAGCUCG 24 9326

BCLllA-9131 - CUGGGCAGCCCCAGCUCG 18 9327

BCLllA-9132 - GCUGGGCAGCCCCAGCUCG 19 9328

BCLllA-9133 - UGCUGGGCAGCCCCAGCUCG 20 9329

BCLllA-9134 - CUGCUGGGCAGCCCCAGCUCG 21 9330

BCLllA-9135 - GCUGCUGGGCAGCCCCAGCUCG 22 9331

BCLllA-9136 - UGCUGCUGGGCAGCCCCAGCUCG 23 9332

BCLllA-9137 - CUGCUGCUGGGCAGCCCCAGCUCG 24 9333

BCLllA-9138 - AGGAAGAGGAAGAAGAGG 18 9334

BCLllA-9139 - GAGGAAGAGGAAGAAGAGG 19 9335

BCLllA-3451 - CGAGGAAGAGGAAGAAGAGG 20 9336

BCLllA-9140 - ACGAGGAAGAGGAAGAAGAGG 21 9337

BCLllA-9141 - GACGAGGAAGAGGAAGAAGAGG 22 9338

BCLllA-9142 - CGACGAGGAAGAGGAAGAAGAGG 23 9339

BCLllA-9143 - ACGACGAGGAAGAGGAAGAAGAGG 24 9340

BCLllA-9144 - AGGACGACGAGGAAGAGG 18 9341

BCLllA-9145 - GAGGACGACGAGGAAGAGG 19 9342

BCLllA-3957 - GGAGGACGACGAGGAAGAGG 20 9343

BCLllA-9146 - AGGAGGACGACGAGGAAGAGG 21 9344

BCLllA-9147 - GAGGAGGACGACGAGGAAGAGG 22 9345

BCLllA-9148 - AGAGGAGGACGACGAGGAAGAGG 23 9346

BCLllA-9149 - AAGAGGAGGACGACGAGGAAGAGG 24 9347

BCLllA-9150 - AAGAAGAGGAGGAAGAGG 18 9348

BCLllA-9151 - GAAGAAGAGGAGGAAGAGG 19 9349

BCLllA-3452 - GGAAGAAGAGGAGGAAGAGG 20 9350

BCLllA-9152 - AGGAAGAAGAGGAGGAAGAGG 21 9351

BCLllA-9153 - GAGGAAGAAGAGGAGGAAGAGG 22 9352

BCLllA-9154 - AGAGGAAGAAGAGGAGGAAGAGG 23 9353 BCLllA-9155 - AAGAGGAAGAAGAGGAGGAAGAGG 24 9354

BCLllA-9156 - CUGACGGAGAGCGAGAGG 18 9355

BCLllA-9157 - GCUGACGGAGAGCGAGAGG 19 9356

BCLllA-9158 - AGCUGACGGAGAGCGAGAGG 20 9357

BCLllA-9159 - GAGCUGACGGAGAGCGAGAGG 21 9358

BCLllA-9160 - GGAGCUGACGGAGAGCGAGAGG 22 9359

BCLllA-9161 - AGGAGCUGACGGAGAGCGAGAGG 23 9360

BCLllA-9162 - GAGGAGCUGACGGAGAGCGAGAGG 24 9361

BCLllA-9163 - AAGAGGAGGACGACGAGG 18 9362

BCLllA-9164 - GAAGAGGAGGACGACGAGG 19 9363

BCLllA-3960 - GGAAGAGGAGGACGACGAGG 20 9364

BCLllA-9165 - AGGAAGAGGAGGACGACGAGG 21 9365

BCLllA-9166 - GAGGAAGAGGAGGACGACGAGG 22 9366

BCLllA-9167 - GGAGGAAGAGGAGGACGACGAGG 23 9367

BCLllA-9168 - AGGAGGAAGAGGAGGACGACGAGG 24 9368

BCLllA-9169 - CGGAGAACGGGGACGAGG 18 9369

BCLllA-9170 - CCGGAGAACGGGGACGAGG 19 9370

BCLllA-3330 - CCCGGAGAACGGGGACGAGG 20 9371

BCLllA-9171 - UCCCGGAGAACGGGGACGAGG 21 9372

BCLllA-9172 - AUCCCGGAGAACGGGGACGAGG 22 9373

BCLllA-9173 - GAUCCCGGAGAACGGGGACGAGG 23 9374

BCLllA-9174 - UGAUCCCGGAGAACGGGGACGAGG 24 9375

BCLllA-9175 - GCGGCCACCUGGCCGAGG 18 9376

BCLllA-9176 - CGCGGCCACCUGGCCGAGG 19 9377

BCLllA-9177 - GCGCGGCCACCUGGCCGAGG 20 9378

BCLllA-9178 - AGCGCGGCCACCUGGCCGAGG 21 9379

BCLllA-9179 - AAGCGCGGCCACCUGGCCGAGG 22 9380

BCLllA-9180 - UAAGCGCGGCCACCUGGCCGAGG 23 9381

BCLllA-9181 - AUAAGCGCGGCCACCUGGCCGAGG 24 9382

BCLllA-9182 - AAGAGGAAGAAGAGGAGG 18 9383

BCLllA-9183 - GAAGAGGAAGAAGAGGAGG 19 9384

BCLllA-3963 - GGAAGAGGAAGAAGAGGAGG 20 9385

BCLllA-9184 - AGGAAGAGGAAGAAGAGGAGG 21 9386

BCLllA-9185 - GAGGAAGAGGAAGAAGAGGAGG 22 9387

BCLllA-9186 - CGAGGAAGAGGAAGAAGAGGAGG 23 9388

BCLllA-9187 - ACGAGGAAGAGGAAGAAGAGGAGG 24 9389

BCLllA-9188 - AAGAGGAGGAAGAGGAGG 18 9390

BCLllA-9189 - GAAGAGGAGGAAGAGGAGG 19 9391

BCLllA-3454 - AGAAGAGGAGGAAGAGGAGG 20 9392

BCLllA-9190 - AAG AAG AG G AG G AAG AG G AG G 21 9393

BCLllA-9191 - GAAGAAGAGGAGGAAGAGGAGG 22 9394

BCLllA-9192 - GGAAGAAGAGGAGGAAGAGGAGG 23 9395 BCLllA-9193 - AGGAAGAAGAGGAGGAAGAGGAGG 24 9396

BCLllA-9194 - AGAACGGGGACGAGGAGG 18 9397

BCLllA-9195 - GAGAACGGGGACGAGGAGG 19 9398

BCLllA-3918 - GGAGAACGGGGACGAGGAGG 20 9399

BCLllA-9196 - CGGAGAACGGGGACGAGGAGG 21 9400

BCLllA-9197 - CCGGAGAACGGGGACGAGGAGG 22 9401

BCLllA-9198 - CCCGGAGAACGGGGACGAGGAGG 23 9402

BCLllA-9199 - UCCCGGAGAACGGGGACGAGGAGG 24 9403

BCLllA-9200 - AGGAGGAAGAGGAGGAGG 18 9404

BCLllA-9201 - GAGGAGGAAGAGGAGGAGG 19 9405

BCLllA-3455 - AGAGGAGGAAGAGGAGGAGG 20 9406

BCLllA-9202 - AAGAGGAGGAAGAGGAGGAGG 21 9407

BCLllA-9203 - GAAGAGGAGGAAGAGGAGGAGG 22 9408

BCLllA-9204 - AGAAGAGGAGGAAGAGGAGGAGG 23 9409

BCLllA-9205 - AAGAAGAGGAGGAAGAGGAGGAGG 24 9410

BCLllA-9206 - ACCGGCGCAGCCACACGG 18 9411

BCLllA-9207 - CACCGGCGCAGCCACACGG 19 9412

BCLllA-3764 - GCACCGGCGCAGCCACACGG 20 9413

BCLllA-9208 - UGCACCGGCGCAGCCACACGG 21 9414

BCLllA-9209 - GUGCACCGGCGCAGCCACACGG 22 9415

BCLllA-9210 - GGUGCACCGGCGCAGCCACACGG 23 9416

BCLllA-9211 - UGGUGCACCGGCGCAGCCACACGG 24 9417

BCLllA-9212 - UAGAGCGCCUGGGGGCGG 18 9418

BCLllA-9213 - AUAGAGCGCCUGGGGGCGG 19 9419

BCLllA-9214 - CAUAGAGCGCCUGGGGGCGG 20 9420

BCLllA-9215 - GCAUAGAGCGCCUGGGGGCGG 21 9421

BCLllA-9216 - CGCAUAGAGCGCCUGGGGGCGG 22 9422

BCLllA-9217 - CCGCAUAGAGCGCCUGGGGGCGG 23 9423

BCLllA-9218 - ACCGCAUAGAGCGCCUGGGGGCGG 24 9424

BCLllA-9219 - AUGUGUGGCAGUUUUCGG 18 9425

BCLllA-9220 - GAUGUGUGGCAGUUUUCGG 19 9426

BCLllA-9221 - AGAUGUGUGGCAGUUUUCGG 20 9427

BCLllA-9222 - AAGAUGUGUGGCAGUUUUCGG 21 9428

BCLllA-9223 - CAAGAUGUGUGGCAGUUUUCGG 22 9429

BCLllA-9224 - UCAAGAUGUGUGGCAGUUUUCGG 23 9430

BCLllA-9225 - CUCAAGAUGUGUGGCAGUUUUCGG 24 9431

BCLllA-9226 - AAUUUGAAGCCCCCAGGG 18 9432

BCLllA-9227 - AAAUUUGAAGCCCCCAGGG 19 9433

BCLllA-9228 - AAAAUUUGAAGCCCCCAGGG 20 9434

BCLllA-9229 - GAAAAUUUGAAGCCCCCAGGG 21 9435

BCLllA-9230 - AGAAAAUUUGAAGCCCCCAGGG 22 9436

BCLllA-9231 - GAGAAAAUUUGAAGCCCCCAGGG 23 9437 BCLllA-9232 - UGAGAAAAUUUGAAGCCCCCAGGG 24 9438

BCLllA-9233 - GUGGACUACGGCUUCGGG 18 9439

BCLllA-9234 - GGUGGACUACGGCUUCGGG 19 9440

BCLllA-9235 - GGGUGGACUACGGCUUCGGG 20 9441

BCLllA-9236 - AGGGUGGACUACGGCUUCGGG 21 9442

BCLllA-9237 - GAGGGUGGACUACGGCUUCGGG 22 9443

BCLllA-9238 - AGAGGGUGGACUACGGCUUCGGG 23 9444

BCLllA-9239 - GAGAGGGUGGACUACGGCUUCGGG 24 9445

BCLllA-9240 - UGAUCCCGGAGAACGGGG 18 9446

BCLllA-9241 - CUGAUCCCGGAGAACGGGG 19 9447

BCLllA-9242 - CCUGAUCCCGGAGAACGGGG 20 9448

BCLllA-9243 - ACCUGAUCCCGGAGAACGGGG 21 9449

BCLllA-9244 - AACCUGAUCCCGGAGAACGGGG 22 9450

BCLllA-9245 - CAACCUGAUCCCGGAGAACGGGG 23 9451

BCLllA-9246 - CCAACCUGAUCCCGGAGAACGGGG 24 9452

BCLllA-9247 - GCAUAGAGCGCCUGGGGG 18 9453

BCLllA-9248 - CGCAUAGAGCGCCUGGGGG 19 9454

BCLllA-6143 - CCGCAUAGAGCGCCUGGGGG 20 9455

BCLllA-9249 - ACCGCAUAGAGCGCCUGGGGG 21 9456

BCLllA-9250 - CACCGCAUAGAGCGCCUGGGGG 22 9457

BCLllA-9251 - CCACCGCAUAGAGCGCCUGGGGG 23 9458

BCLllA-9252 - CCCACCGCAUAGAGCGCCUGGGGG 24 9459

BCLllA-9253 - CGCAUAGAGCGCCUGGGG 18 9460

BCLllA-9254 - CCGCAUAGAGCGCCUGGGG 19 9461

BCLllA-9255 - ACCGCAUAGAGCGCCUGGGG 20 9462

BCLllA-9256 - CACCGCAUAGAGCGCCUGGGG 21 9463

BCLllA-9257 - CCACCGCAUAGAGCGCCUGGGG 22 9464

BCLllA-9258 - CCCACCGCAUAGAGCGCCUGGGG 23 9465

BCLllA-9259 - CCCCACCGCAUAGAGCGCCUGGGG 24 9466

BCLllA-9260 - AUAAGCGCGGCCACCUGG 18 9467

BCLllA-9261 - CAUAAGCGCGGCCACCUGG 19 9468

BCLllA-9262 - GCAUAAGCGCGGCCACCUGG 20 9469

BCLllA-9263 - AGCAUAAGCGCGGCCACCUGG 21 9470

BCLllA-9264 - AAGCAUAAGCGCGGCCACCUGG 22 9471

BCLllA-9265 - GAAGCAUAAGCGCGGCCACCUGG 23 9472

BCLllA-9266 - AGAAGCAUAAGCGCGGCCACCUGG 24 9473

BCLllA-9267 - GAGAGGCUUCCGGCCUGG 18 9474

BCLllA-9268 - AGAGAGGCUUCCGGCCUGG 19 9475

BCLllA-9269 - GAGAGAGGCUUCCGGCCUGG 20 9476

BCLllA-9270 - CGAGAGAGGCUUCCGGCCUGG 21 9477

BCLllA-9271 - UCGAGAGAGGCUUCCGGCCUGG 22 9478

BCLllA-9272 - AUCGAGAGAGGCUUCCGGCCUGG 23 9479 BCLllA-9273 - UAUCGAGAGAGGCUUCCGGCCUGG 24 9480

BCLllA-9274 - CCUUCCACCAGGUCCUGG 18 9481

BCLllA-9275 - GCCUUCCACCAGGUCCUGG 19 9482

BCLllA-9276 - GGCCUUCCACCAGGUCCUGG 20 9483

BCLllA-9277 - AGGCCUUCCACCAGGUCCUGG 21 9484

BCLllA-9278 - GAGGCCUUCCACCAGGUCCUGG 22 9485

BCLllA-9279 - CGAGGCCUUCCACCAGGUCCUGG 23 9486

BCLllA-9280 - GCGAGGCCUUCCACCAGGUCCUGG 24 9487

BCLllA-9281 - GGAGACUUAGAGAGCUGG 18 9488

BCLllA-9282 - AGGAGACUUAGAGAGCUGG 19 9489

BCLllA-9283 - UAGGAGACUUAGAGAGCUGG 20 9490

BCLllA-9284 - CUAGGAGACUUAGAGAGCUGG 21 9491

BCLllA-9285 - UCUAGGAGACUUAGAGAGCUGG 22 9492

BCLllA-9286 - CUCUAGGAGACUUAGAGAGCUGG 23 9493

BCLllA-9287 - UCUCUAGGAGACUUAGAGAGCUGG 24 9494

BCLllA-9288 - CACCGCCCGGGGAGCUGG 18 9495

BCLllA-9289 - ACACCGCCCGGGGAGCUGG 19 9496

BCLllA-9290 - CACACCGCCCGGGGAGCUGG 20 9497

BCLllA-9291 - CCACACCGCCCGGGGAGCUGG 21 9498

BCLllA-9292 - UCCACACCGCCCGGGGAGCUGG 22 9499

BCLllA-9293 - CUCCACACCGCCCGGGGAGCUGG 23 9500

BCLllA-9294 - UCUCCA CACCGCCCGGGGAGCUGG 24 9501

BCLllA-9295 - CAGCGGCACGGGAAGUGG 18 9502

BCLllA-9296 - GCAGCGGCACGGGAAGUGG 19 9503

BCLllA-6157 - CGCAGCGGCACGGGAAGUGG 20 9504

BCLllA-9297 - GCGCAGCGGCACGGGAAGUGG 21 9505

BCLllA-9298 - GGCGCAGCGGCACGGGAAGUGG 22 9506

BCLllA-9299 - GGGCGCAGCGGCACGGGAAGUGG 23 9507

BCLllA-9300 - GGGGCGCAGCGGCACGGGAAGUGG 24 9508

BCLllA-9301 - GCCCUGCCCGACGUCAUG 18 9509

BCLllA-9302 - CGCCCUGCCCGACGUCAUG 19 9510

BCLllA-9303 - GCGCCCUGCCCGACGUCAUG 20 9511

BCLllA-9304 - CGCGCCCUGCCCGACGUCAUG 21 9512

BCLllA-9305 - CCGCGCCCUGCCCGACGUCAUG 22 9513

BCLllA-9306 - GCCGCGCCCUGCCCGACGUCAUG 23 9514

BCLllA-9307 - AGCCGCGCCCUGCCCGACGUCAUG 24 9515

BCLllA-9308 - CGACACUUGUGAGUACUG 18 9516

BCLllA-9309 - GCGACACUUGUGAGUACUG 19 9517

BCLllA-6169 - AGCGACACUUGUGAGUACUG 20 9518

BCLllA-9310 - CAGCGACACUUGUGAGUACUG 21 9519

BCLllA-9311 - GCAGCGACACUUGUGAGUACUG 22 9520

BCLllA-9312 - CGCAGCGACACUUGUGAGUACUG 23 9521 BCLllA-9313 - ACGCAGCGACACUUGUGAGUACUG 24 9522

BCLllA-9314 - GAGGAGGAGGAGGAGCUG 18 9523

BCLllA-9315 - AGAGGAGGAGGAGGAGCUG 19 9524

BCLllA-9316 - AAGAGGAGGAGGAGGAGCUG 20 9525

BCLllA-9317 - GAAGAGGAGGAGGAGGAGCUG 21 9526

BCLllA-9318 - GGAAGAGGAGGAGGAGGAGCUG 22 9527

BCLllA-9319 - AGGAAGAGGAGGAGGAGGAGCUG 23 9528

BCLllA-9320 - GAGGAAGAGGAGGAGGAGGAGCUG 24 9529

BCLllA-9321 - CUGUCCAAAAAGCUGCUG 18 9530

BCLllA-9322 - CCUGUCCAAAAAGCUGCUG 19 9531

BCLllA-9323 - GCCUGUCCAAAAAGCUGCUG 20 9532

BCLllA-9324 - GGCCUGUCCAAAAAGCUGCUG 21 9533

BCLllA-9325 - GGGCCUGUCCAAAAAGCUGCUG 22 9534

BCLllA-9326 - GGGGCCUGUCCAAAAAGCUGCUG 23 9535

BCLllA-9327 - GGGGGCCUGUCCAAAAAGCUGCUG 24 9536

BCLllA-9328 - GCAGCGGCACGGGAAGUG 18 9537

BCLllA-9329 - CGCAGCGGCACGGGAAGUG 19 9538

BCLllA-9330 - GCGCAGCGGCACGGGAAGUG 20 9539

BCLllA-9331 - GGCGCAGCGGCACGGGAAGUG 21 9540

BCLllA-9332 - GGGCGCAGCGGCACGGGAAGUG 22 9541

BCLllA-9333 - GGGGCGCAGCGGCACGGGAAGUG 23 9542

BCLllA-9334 - CGGGGCGCAGCGGCACGGGAAGUG 24 9543

BCLllA-9335 - CCCGGCACCAGCGACUUG 18 9544

BCLllA-9336 - ACCCGGCACCAGCGACUUG 19 9545

BCLllA-9337 - AACCCGGCACCAGCGACUUG 20 9546

BCLllA-9338 - GAACCCGGCACCAGCGACUUG 21 9547

BCLllA-9339 - GGAACCCGGCACCAGCGACUUG 22 9548

BCLllA-9340 - CGGAACCCGGCACCAGCGACUUG 23 9549

BCLllA-9341 - CCGGAACCCGGCACCAGCGACUUG 24 9550

BCLllA-9342 - CUUAAGUUCUGAGAAAAU 18 9551

BCLllA-9343 - CCUUAAGUUCUGAGAAAAU 19 9552

BCLllA-9344 - CCCUUAAGUUCUGAGAAAAU 20 9553

BCLllA-9345 - GCCCUUAAGUUCUGAGAAAAU 21 9554

BCLllA-9346 - AGCCCUUAAGUUCUGAGAAAAU 22 9555

BCLllA-9347 - GAGCCCUUAAGUUCUGAGAAAAU 23 9556

BCLllA-9348 - AGAGCCCUUAAGUUCUGAGAAAAU 24 9557

BCLllA-9349 - GGAUUUCUCUAGGAGACU 18 9558

BCLllA-9350 - UGGAUUUCUCUAGGAGACU 19 9559

BCLllA-9351 - AUGGAUUUCUCUAGGAGACU 20 9560

BCLllA-9352 - CAUGGAUUUCUCUAGGAGACU 21 9561

BCLllA-9353 - CCAUGGAUUUCUCUAGGAGACU 22 9562

BCLllA-9354 - GCCAUGGAUUUCUCUAGGAGACU 23 9563 BCLllA-9355 - CGCCAUGGAUUUCUCUAGGAGACU 24 9564

BCLllA-9356 - AUGGAUUAAGAAUCUACU 18 9565

BCLllA-9357 - CAUGGAUUAAGAAUCUACU 19 9566

BCLllA-9358 - UCAUGGAUUAAGAAUCUACU 20 9567

BCLllA-9359 - CUCAUGGAUUAAGAAUCUACU 21 9568

BCLllA-9360 - ACUCAUGGAUUAAGAAUCUACU 22 9569

BCLllA-9361 - CACUCAUGGAUUAAGAAUCUACU 23 9570

BCLllA-9362 - ACACUCAUGGAUUAAGAAUCUACU 24 9571

BCLllA-9363 - GCGACACUUGUGAGUACU 18 9572

BCLllA-9364 - AGCGACACUUGUGAGUACU 19 9573

BCLllA-9365 - CAGCGACACUUGUGAGUACU 20 9574

BCLllA-9366 - GCAGCGACACUUGUGAGUACU 21 9575

BCLllA-9367 - CGCAGCGACACUUGUGAGUACU 22 9576

BCLllA-9368 - ACGCAGCGACACUUGUGAGUACU 23 9577

BCLllA-9369 - GACGCAGCGACACUUGUGAGUACU 24 9578

BCLllA-9370 - CCACCGCAUAGAGCGCCU 18 9579

BCLllA-9371 - CCCACCGCAUAGAGCGCCU 19 9580

BCLllA-6197 - CCCCACCGCAUAGAGCGCCU 20 9581

BCLllA-9372 - CCCCCACCGCAUAGAGCGCCU 21 9582

BCLllA-9373 - ACCCCCACCGCAUAGAGCGCCU 22 9583

BCLllA-9374 - GACCCCCACCGCAUAGAGCGCCU 23 9584

BCLllA-9375 - GGACCCCCACCGCAUAGAGCGCCU 24 9585

BCLllA-9376 - CCCCGGGCGAGUCGGCCU 18 9586

BCLllA-9377 - UCCCCGGGCGAGUCGGCCU 19 9587

BCLllA-6200 - CUCCCCGGGCGAGUCGGCCU 20 9588

BCLllA-9378 - GCUCCCCGGGCGAGUCGGCCU 21 9589

BCLllA-9379 - UGCUCCCCGGGCGAGUCGGCCU 22 9590

BCLllA-9380 - CUGCUCCCCGGGCGAGUCGGCCU 23 9591

BCLllA-9381 - GCUGCUCCCCGGGCGAGUCGGCCU 24 9592

BCLllA-9382 - CCUCGUCGGAGCACUCCU 18 9593

BCLllA-9383 - UCCUCGUCGGAGCACUCCU 19 9594

BCLllA-6202 - CUCCUCGUCGGAGCACUCCU 20 9595

BCLllA-9384 - CCUCCUCGUCGGAGCACUCCU 21 9596

BCLllA-9385 - GCCUCCUCGUCGGAGCACUCCU 22 9597

BCLllA-9386 - UGCCUCCUCGUCGGAGCACUCCU 23 9598

BCLllA-9387 - UUGCCUCCUCGUCGGAGCACUCCU 24 9599

BCLllA-9388 - AAGAUCCCUUCCUUAGCU 18 9600

BCLllA-9389 - AAAGAUCCCUUCCUUAGCU 19 9601

BCLllA-9390 - CAAAGAUCCCUUCCUUAGCU 20 9602

BCLllA-9391 - UCAAAGAUCCCUUCCUUAGCU 21 9603

BCLllA-9392 - CUCAAAGAUCCCUUCCUUAGCU 22 9604

BCLllA-9393 - GCUCAAAGAUCCCUUCCUUAGCU 23 9605 BCLllA-9394 - AGCUCAAAGAUCCCUUCCUUAGCU 24 9606

BCLllA-9395 - AGAGGGUGGACUACGGCU 18 9607

BCLllA-9396 - GAGAGGGUGGACUACGGCU 19 9608

BCLllA-9397 - CGAGAGGGUGGACUACGGCU 20 9609

BCLllA-9398 - GCGAGAGGGUGGACUACGGCU 21 9610

BCLllA-9399 - AGCGAGAGGGUGGACUACGGCU 22 9611

BCLllA-9400 - GAGCGAGAGGGUGGACUACGGCU 23 9612

BCLllA-9401 - AGAGCGAGAGGGUGGACUACGGCU 24 9613

BCLllA-9402 - CGGUUGAAUCCAAUGGCU 18 9614

BCLllA-9403 - GCGGUUGAAUCCAAUGGCU 19 9615

BCLllA-9404 - UGCGGUUGAAUCCAAUGGCU 20 9616

BCLllA-9405 - CUGCGGUUGAAUCCAAUGGCU 21 9617

BCLllA-9406 - GCUGCGGUUGAAUCCAAUGGCU 22 9618

BCLllA-9407 - UGCUGCGGUUGAAUCCAAUGGCU 23 9619

BCLllA-9408 - GUGCUGCGGUUGAAUCCAAUGGCU 24 9620

BCLllA-9409 - AGCUGGACGGAGGGAUCU 18 9621

BCLllA-9410 - GAGCUGGACGGAGGGAUCU 19 9622

BCLllA-6210 - GGAGCUGGACGGAGGGAUCU 20 9623

BCLllA-9411 - GGGAGCUGGACGGAGGGAUCU 21 9624

BCLllA-9412 - GGGGAGCUGGACGGAGGGAUCU 22 9625

BCLllA-9413 - CGGGGAGCUGGACGGAGGGAUCU 23 9626

BCLllA-9414 - CCGGGGAGCUGGACGGAGGGAUCU 24 9627

BCLllA-9415 - CCCGCCAUGGAUUUCUCU 18 9628

BCLllA-9416 - UCCCGCCAUGGAUUUCUCU 19 9629

BCLllA-6212 - CUCCCGCCAUGGAUUUCUCU 20 9630

BCLllA-9417 - CCUCCCGCCAUGGAUUUCUCU 21 9631

BCLllA-9418 - GCCUCCCGCCAUGGAUUUCUCU 22 9632

BCLllA-9419 - AGCCUCCCGCCAUGGAUUUCUCU 23 9633

BCLllA-9420 - GAGCCUCCCGCCAUGGAUUUCUCU 24 9634

BCLllA-9421 - CGAGAGCCCUUAAGUUCU 18 9635

BCLllA-9422 - UCGAGAGCCCUUAAGUUCU 19 9636

BCLllA-9423 - CUCGAGAGCCCUUAAGUUCU 20 9637

BCLllA-9424 - GCUCGAGAGCCCUUAAGUUCU 21 9638

BCLllA-9425 - AGCUCGAGAGCCCUUAAGUUCU 22 9639

BCLllA-9426 - AAGCUCGAGAGCCCUUAAGUUCU 23 9640

BCLllA-9427 - GAAGCUCGAGAGCCCUUAAGUUCU 24 9641

BCLllA-9428 - CGCCUUUUGCCUCCUCGU 18 9642

BCLllA-9429 - UCGCCUUUUGCCUCCUCGU 19 9643

BCLllA-6220 - AUCGCCUUUUGCCUCCUCGU 20 9644

BCLllA-9430 - AAUCGCCUUUUGCCUCCUCGU 21 9645

BCLllA-9431 - CAAUCGCCUUUUGCCUCCUCGU 22 9646

BCLllA-9432 - ACAAUCGCCUUUUGCCUCCUCGU 23 9647 BCLllA-9433 - GACAAUCGCCUUUUGCCUCCUCGU 24 9648

BCLllA-9434 - ACGCCCCAUAUUAGUGGU 18 9649

BCLllA-9435 - CACGCCCCAUAUUAGUGGU 19 9650

BCLllA-9436 - GCACGCCCCAUAUUAGUGGU 20 9651

BCLllA-9437 - AGCACGCCCCAUAUUAGUGGU 21 9652

BCLllA-9438 - GAGCACGCCCCAUAUUAGUGGU 22 9653

BCLllA-9439 - GGAGCACGCCCCAUAUUAGUGGU 23 9654

BCLllA-9440 - GGGAGCACGCCCCAUAUUAGUGGU 24 9655

BCLllA-9441 - GACACUUGUGAGUACUGU 18 9656

BCLllA-9442 - CGACACUUGUGAGUACUGU 19 9657

BCLllA-6230 - GCGACACUUGUGAGUACUGU 20 9658

BCLllA-9443 - AGCGACACUUGUGAGUACUGU 21 9659

BCLllA-9444 - CAGCGACACUUGUGAGUACUGU 22 9660

BCLllA-9445 - GCAGCGACACUUGUGAGUACUGU 23 9661

BCLllA-9446 - CGCAGCGACACUUGUGAGUACUGU 24 9662

BCLllA-9447 - CGCGGGUUGGUAUCCCUU 18 9663

BCLllA-9448 - CCGCGGGUUGGUAUCCCUU 19 9664

BCLllA-9449 - CCCGCGGGUUGGUAUCCCUU 20 9665

BCLllA-9450 - CCCCGCGGGUUGGUAUCCCUU 21 9666

BCLllA-9451 - ACCCCGCGGGUUGGUAUCCCUU 22 9667

BCLllA-9452 - GACCCCGCGGGUUGGUAUCCCUU 23 9668

BCLllA-9453 - UGACCCCGCGGGUUGGUAUCCCUU 24 9669

BCLllA-9454 - AGAUCCCUUCCUUAGCUU 18 9670

BCLllA-9455 - AAGAUCCCUUCCUUAGCUU 19 9671

BCLllA-6234 - AAAGAUCCCUUCCUUAGCUU 20 9672

BCLllA-9456 - CAAAGAUCCCUUCCUUAGCUU 21 9673

BCLllA-9457 - UCAAAGAUCCCUUCCUUAGCUU 22 9674

BCLllA-9458 - CUCAAAGAUCCCUUCCUUAGCUU 23 9675

BCLllA-9459 - GCUCAAAGAUCCCUUCCUUAGCUU 24 9676

BCLllA-9460 - CUCGAGAGCCCUUAAGUU 18 9677

BCLllA-9461 - GCUCGAGAGCCCUUAAGUU 19 9678

BCLllA-9462 - AGCUCGAGAGCCCUUAAGUU 20 9679

BCLllA-9463 - AAGCUCGAGAGCCCUUAAGUU 21 9680

BCLllA-9464 - GAAGCUCGAGAGCCCUUAAGUU 22 9681

BCLllA-9465 - GGAAGCUCGAGAGCCCUUAAGUU 23 9682

BCLllA-9466 - UGGAAGCUCGAGAGCCCUUAAGUU 24 9683

BCLllA-9467 - GGCAAGACGUUCAAAUUU 18 9684

BCLllA-9468 - CGGCAAGACGUUCAAAUUU 19 9685

BCLllA-9469 - GCGGCAAGACGUUCAAAUUU 20 9686

BCLllA-9470 - UGCGGCAAGACGUUCAAAUUU 21 9687

BCLllA-9471 - CUGCGGCAAGACGUUCAAAUUU 22 9688

BCLllA-9472 - UCUGCGGCAAGACGUUCAAAUUU 23 9689 BCLllA-9473 - U UCUGCGGCAAGACGUUCAAAUUU 24 9690

Table 14A provides exemplary targeting domains for knocking out the BCL11A gene selected according to the first tier parameters. The targeting domains bind within the first 500 bp of the coding sequence (e.g., within 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 14A

Table 14B provides exemplary targeting domains for knocking out the BCL11A gene selected according to the third 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 14B

BCLllA-9517 + GCGAGCUGGGGCUGCCCAGC 20 9743

BCLllA-9518 - AUGGCUAUGGAGCCUCCCGC 20 9744

BCLllA-9519 + CCUCGGCCAGGUGGCCGCGC 20 9745

BCLllA-9520 + UGUGCGUCUUCAUGUGGCGC 20 9746

BCLllA-7725 + UUCUCAGAACUUAAGGGCUC 20 9747

BCLllA-9521 - GGCAGCUCAAAGAUCCCUUC 20 9748

BCLllA-7752 + GGGGCAGGUCGAACUCCUUC 20 9749

BCLllA-9522 + GGGGGGGCGUCGCCAGGAAG 20 9750

BCLllA-9523 - AUACCAGGAUCAGUAUCGAG 20 9751

BCLllA-9524 + GGGGGCUGGGAGGGAGGAGG 20 9752

BCLllA-9525 + UCGGACUUGACCGUCAUGGG 20 9753

BCLllA-9526 + CCUCGGCCUCGGCCAGGUGG 20 9754

BCLllA-6165 + UGUGCAUGUGCGUCUUCAUG 20 9755

BCLllA-8204 + GGUCGCACAGGUUGCACUUG 20 9756

BCLllA-9527 + CGAACUCCUUCUCGAGCUUG 20 9757

BCLllA-9528 - UGCAACACGCACAGAACACU 20 9758

BCLllA-9529 - ACUCCUCGGAGAACGGGAGU 20 9759

BCLllA-9530 + CGGGGUCAGGGGACUUCCGU 20 9760

Table 15A provides exemplary targeting domains for knocking down the BCLl 1 A 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) 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 BCLl 1 A gene (e.g., reduce or

eliminateBCLl 1 A gene expression, BCLl 1 A protein function, or the level of BCLl 1 A protein). One or more gRNA may be used to target an eiCas9 to the promoter region of the BCLl 1 A gene.

Table 15A

BCLllA-9535 - GCGCUCGCUGCGGCCAC 17 9767

BCLllA-4560 + ACGCCAGACGCGGCCCC 17 9768

BCLllA-9536 + U UCACAUCGGGAGAGCC 17 9769

BCLllA-9537 + GU UCACAUCGGGAGAGC 17 9770

BCLllA-9538 - UAAUCACGAGAGCGCGC 17 9771

BCLllA-9539 - CUGACGUUCAAGUUCGC 17 9772

BCLllA-5327 + CCCGUUUGCUUAAGUGC 17 9773

BCLllA-9540 + ACGGCUCGGUUCACAUC 17 9774

BCLllA-9541 + CUUGAACGUCAGGAGUC 17 9775

BCLllA-9542 + CUGCGAACUUGAACGUC 17 9776

BCLllA-9543 - CCCCCGGGGGCCGCGUC 17 9777

BCLllA-9544 + UCCGCGGACGCCAGACG 17 9778

BCLllA-9545 - G ACU AG AAG CAAAAG CG 17 9779

BCLllA-5335 + AGACAUGGUGGGCUGCG 17 9780

BCLllA-9546 - AAAACCU CCG AG AG U CG 17 9781

BCLllA-9547 + U UUACCUCGACUCUCGG 17 9782

BCLllA-9548 - AGUCCGCGUGUGUGGGG 17 9783

BCLllA-5336 + CGUUUGCU UAAGUGCUG 17 9784

BCLllA-9549 - UAGAGUCCGCGUGUGUG 17 9785

BCLllA-9550 + GACGGCUCGGUUCACAU 17 9786

BCLllA-9551 - CUCCCCGCACUGGCCAU 17 9787

BCLllA-9552 + CGGCAAUGGUUCCAGAU 17 9788

BCLllA-9553 + GCGGGCGGACGACGGCU 17 9789

BCLllA-5338 + CCGUUUGCUUAAGUGCU 17 9790

BCLllA-5340 + UUGCGGCGAGACAUGGU 17 9791

BCLllA-9554 + CGUGGCCGGGAGAGAAGAAA 20 9792

BCLllA-5345 + GCCUUGCUUGCGGCGAGACA 20 9793

BCLllA-5346 - ACCAUGUCUCGCCGCAAGCA 20 9794

BCLllA-9555 - UCCUGACGUUCAAGUUCGCA 20 9795

BCLllA-9556 + ACACCAAUGGACACACAUCA 20 9796

BCLllA-9557 + UACACGGCAAUGGUUCCAGA 20 9797

BCLllA-9558 + GCCAAUGGCCAGUGCGGGGA 20 9798

BCLllA-9559 + AAUGGUUCCAGAUGGGAUGA 20 9799

BCLllA-9560 - GAGUCUCCUUCUU UCUAACC 20 9800

BCLllA-9561 + CGGUUCACAUCGGGAGAGCC 20 9801

BCLllA-9562 + UCGGUUCACAUCGGGAGAGC 20 9802

BCLllA-9563 - CCGCGUGUGUGGGGGGGAGC 20 9803

BCLllA-9564 - UAAUAAUCACGAGAGCGCGC 20 9804

BCLllA-9565 + AAAUAAUACAAAGAUGGCGC 20 9805

BCLllA-9566 - CUCCUGACGU UCAAGUUCGC 20 9806

BCLllA-9567 + GAGACACACAAAACAUGGGC 20 9807

BCLllA-5352 + AUUCCCGUUUGCU UAAGUGC 20 9808 BCLllA-9568 + ACGACGGCUCGGUUCACAUC 20 9809

BCLllA-9569 - CGCACUUGAACUUGCAGCUC 20 9810

BCLllA-9570 + UCCCUGCGAACUUGAACGUC 20 9811

BCLllA-9571 - U CG AGG U AAAAG AG AU AAAG 20 9812

BCLllA-9572 + CCAAUGGCCAGUGCGGGGAG 20 9813

BCLllA-4351 + GACGCCAGACGCGGCCCCCG 20 9814

BCLllA-9573 - UGCGGCCACUGGUGAGCCCG 20 9815

BCLllA-9574 - GGGGCCGCGUCUGGCGUCCG 20 9816

BCLllA-5359 + GCGAGACAUGGUGGGCUGCG 20 9817

BCLllA-9575 - AGAAAAACCUCCGAGAGUCG 20 9818

BCLllA-4561 + ACGCCAGACGCGGCCCCCGG 20 9819

BCLllA-9576 + UCU UUUACCUCGACUCUCGG 20 9820

BCLllA-9577 - UAGAGUCCGCGUGUGUGGGG 20 9821

BCLllA-9578 - UUUAGAGUCCGCGUGUGUGG 20 9822

BCLllA-9579 + CAAUGGUUCCAGAUGGGAUG 20 9823

BCLllA-5361 + CGGCGAGACAUGGUGGGCUG 20 9824

BCLllA-9580 + CUGAGCUGCAAGU UCAAGUG 20 9825

BCLllA-9581 - CAUUUUAGAGUCCGCGUGUG 20 9826

BCLllA-9582 + GACGACGGCUCGGUUCACAU 20 9827

BCLllA-9583 - AGCCCCUGAUGUGUGUCCAU 20 9828

BCLllA-9584 + GCGGCGGGCGGACGACGGCU 20 9829

BCLllA-9585 + AUCUCUUU UACCUCGACUCU 20 9830

BCLllA-5365 + UGCUUGCGGCGAGACAUGGU 20 9831

BCLllA-9586 - AUUUUAGAGUCCGCGUGUGU 20 9832

Table 15B provides exemplary targeting domains for knocking down the BCLl 1 A 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). 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 BCLl 1 A gene (e.g., reduce or eliminate BCLl 1A gene expression, BCLl 1A protein function, or the level of BCLl 1 A protein). One or more gRNA may be used to target an eiCas9 to the promoter region of the BCLl 1A gene.

Table 15B

BCLllA-9587 + GAGAGAGAUGAAAAAAA 17 9833

BCLllA-5369 - CCCAGCACUUAAGCAAA 17 9834

BCLllA-9588 - UUAUUUUGGAUGUCAAA 17 9835

BCLllA-4473 + GGCCGGGAGAGAAGAAA 17 9836

BCLllA-9589 + GCAGGGGUGGGAGGAAA 17 9837

BCLllA-9590 - G AGG U AAAAG AG AU AAA 17 9838

BCLllA-9591 + AAU U AAAU AAAAU U AAA 17 9839

BCLllA-9592 + GGGGAAGCUCACACCAA 17 9840

BCLllA-4574 + AGACCAGGACAAGCCAA 17 9841

BCLllA-9593 + UGGCCGGGAGAGAAGAA 17 9842

BCLllA-4491 + GGGCGAGCAGGAGAGAA 17 9843

BCLllA-9594 + GGCAGGGGUGGGAGGAA 17 9844

BCLllA-4570 + AGAAGGGGAGGAGGGAA 17 9845

BCLllA-9595 - CG AGG U AAAAG AG AU AA 17 9846

BCLllA-4625 + CAGAGACACACAAAACA 17 9847

BCLllA-9596 + U C U C A A A AG U G C A U AC A 17 9848

BCLllA-9597 - GUGUGUGGGGGGGAGCA 17 9849

BCLllA-9598 + A A U AC A A AG A U G G CG C A 17 9850

BCLllA-9599 + CACACAAAACAUGGGCA 17 9851

BCLllA-9600 + AGAAGAAAGGGGUGGCA 17 9852

BCLllA-9601 + CCAAUGGACACACAUCA 17 9853

BCLllA-9602 - CUUGAACUUGCAGCUCA 17 9854

BCLllA-4529 + AAAAAAAAAAAAAAAGA 17 9855

BCLllA-9603 + U AG AAA U A A U AC A A AG A 17 9856

BCLllA-9604 + GAGCCGGGUUAGAAAGA 17 9857

BCLllA-4592 + AGGGCGAGCAGGAGAGA 17 9858

BCLllA-4534 - AAAGCGAGGGGGAGAGA 17 9859

BCLllA-9605 + GAGAGAAGAGAGAUAGA 17 9860

BCLllA-4674 + CGGCGGCGGGCGGACGA 17 9861

BCLllA-4494 + GGGGAGGGGCGGGCCGA 17 9862

BCLllA-9606 - ACU AG AAG CAAAAG CG A 17 9863

BCLllA-4591 + AGGAGAGAAGGGGAGGA 17 9864

BCLllA-4399 + GAGAAGGGGAGGAGGGA 17 9865

BCLllA-4499 + GGGGCGGGCCGAGGGGA 17 9866

BCLllA-9607 + AAUGGCCAGUGCGGGGA 17 9867

BCLllA-4562 + ACGCGGCCCCCGGGGGA 17 9868

BCLllA-9608 + AACGUCAGGAGUCUGGA 17 9869

BCLllA-9609 - U U A A A A A A A AG C C A U G A 17 9870

BCLllA-9610 + GGUUCCAGAUGGGAUGA 17 9871

BCLllA-5383 - CCAGCACUUAAGCAAAC 17 9872

BCLllA-9611 - CCUCCCCCUCCCCGCAC 17 9873

BCLllA-9612 - UCUCCU UCUUUCUAACC 17 9874 BCLllA-9613 + GACAUGAAAAAGAGACC 17 9875

BCLllA-4662 + CGCCAGACGCGGCCCCC 17 9876

BCLllA-9614 - CGGCCCGCCCCUCCCCC 17 9877

BCLllA-9615 - UCGGCCCGCCCCUCCCC 17 9878

BCLllA-9616 + GCGGCGGUGGCGUGGCC 17 9879

BCLllA-9617 - ACCCCUU UCU UCUCUCC 17 9880

BCLllA-9618 - UGGCCAUUGGCUUGUCC 17 9881

BCLllA-9619 + ACAUGGGCAGGGCGAGC 17 9882

BCLllA-9620 - CGUGUGUGGGGGGGAGC 17 9883

BCLllA-9621 + GGGGGCGCUGGGGCCGC 17 9884

BCLllA-4646 + CCGAGGGGAGGGGGCGC 17 9885

BCLllA-9622 + UAAUACAAAGAUGGCGC 17 9886

BCLllA-4441 + GCGGCGGCGGCGGCGGC 17 9887

BCLllA-9623 + GGACACACAUCAGGGGC 17 9888

BCLllA-4429 + GCCCCCGGGGGAGGGGC 17 9889

BCLllA-5392 + AUGGUGGGCUGCGGGGC 17 9890

BCLllA-9624 + AGGGGGAGGUGCGGGGC 17 9891

BCLllA-9625 + ACACACAAAACAUGGGC 17 9892

BCLllA-9626 + CGCGGCGGUGGCGUGGC 17 9893

BCLllA-9627 + GAGAAGAAAGGGGUGGC 17 9894

BCLllA-5395 + GAGACAUGGUGGGCUGC 17 9895

BCLllA-9628 + AAGCCAAUGGCCAGUGC 17 9896

BCLllA-9629 + CGGGGAGGGGGAGGUGC 17 9897

BCLllA-9630 + ACCAAUGGACACACAUC 17 9898

BCLllA-9631 - AAAACCCUCAUCCCAUC 17 9899

BCLllA-9632 - ACUUGAACUUGCAGCUC 17 9900

BCLllA-9633 - GAUGAAGAUAUUUUCUC 17 9901

BCLllA-4528 + AAAAAAAAAAAAAAAAG 17 9902

BCLllA-4433 + GCCGGGAGAGAAGAAAG 17 9903

BCLllA-9634 - AG G U A A A AG AG A U A A AG 17 9904

BCLllA-4475 + GG CG AG CAGG AG AG AAG 17 9905

BCLllA-4389 + GAAGGGGAGGAGGGAAG 17 9906

BCLllA-9635 + GGCCGCGGGCUCACCAG 17 9907

BCLllA-9636 + G A AG A A AG GGGUGGCAG 17 9908

BCLllA-9637 + CAAUGGACACACAUCAG 17 9909

BCLllA-9638 - UUGAACUUGCAGCUCAG 17 9910

BCLllA-4543 - AAGCGAGGGGGAGAGAG 17 9911

BCLllA-4533 - AAAAGCGAGGGGGAGAG 17 9912

BCLllA-4485 + GGGAGGGGCGGGCCGAG 17 9913

BCLllA-9639 - CUAGAAGCAAAAGCGAG 17 9914

BCLllA-4492 + GGGCGGGCCGAGGGGAG 17 9915

BCLllA-9640 + AUGGCCAGUGCGGGGAG 17 9916 BCLllA-4665 + CGCGGCCCCCGGGGGAG 17 9917

BCLllA-9641 + AGAGAGAAGAGAGAUAG 17 9918

BCLllA-9642 + GCUCCCCCCCACACACG 17 9919

BCLllA-4427 + GCCAGACGCGGCCCCCG 17 9920

BCLllA-9643 - GGCCCGCCCCUCCCCCG 17 9921

BCLllA-9644 - GGCCACUGGUGAGCCCG 17 9922

BCLllA-4670 - CGGCCACGCCACCGCCG 17 9923

BCLllA-4470 + GGCCGCAGCGAGCGCCG 17 9924

BCLllA-4502 + GGGGGAGGGGCGGGCCG 17 9925

BCLllA-9645 + AGGGGGCGCUGGGGCCG 17 9926

BCLllA-9646 + CGGGGCGGGGGGCUCCG 17 9927

BCLllA-9647 - GCCGCGUCUGGCGUCCG 17 9928

BCLllA-9648 + GGGGGAGGUGCGGGGCG 17 9929

BCLllA-9649 + GCGCCGCGGCGGUGGCG 17 9930

BCLllA-9650 + AGCCAAUGGCCAGUGCG 17 9931

BCLllA-9651 + GGGGAGGGGGAGGUGCG 17 9932

BCLllA-9652 - G G U A A A AG AG A U A A AG G 17 9933

BCLllA-9653 - UGAACUUGCAGCUCAGG 17 9934

BCLllA-9654 - U AG AAG CAAAAG CG AGG 17 9935

BCLllA-4627 + CAGGAGAGAAGGGGAGG 17 9936

BCLllA-4480 + GGCGGGCCGAGGGGAGG 17 9937

BCLllA-9655 + UGGCCAGUGCGGGGAGG 17 9938

BCLllA-4634 + CCAGACGCGGCCCCCGG 17 9939

BCLllA-9656 - GCCCGCCCCUCCCCCGG 17 9940

BCLllA-4660 + CG CAG CG AG CG CCG CG G 17 9941

BCLllA-4588 + AGCGAGCGCCGCGGCGG 17 9942

BCLllA-4478 + GGCGGCGGCGGCGGCGG 17 9943

BCLllA-4447 + GCGGGCGGCGGCGGCGG 17 9944

BCLllA-4500 + GGGGCGGGCGGCGGCGG 17 9945

BCLllA-5409 + UGCGGGGCGGGCGGCGG 17 9946

BCLllA-5410 + GGCUGCGGGGCGGGCGG 17 9947

BCLllA-9657 + GGGGAGGUGCGGGGCGG 17 9948

BCLllA-9658 + GGGGUGGGAGGAAAGGG 17 9949

BCLllA-9659 - GAACUUGCAGCUCAGGG 17 9950

BCLllA-4444 + GCGGCGGCGGCGGCGGG 17 9951

BCLllA-5411 + GUGGGCUGCGGGGCGGG 17 9952

BCLllA-9660 + GGGAGGUGCGGGGCGGG 17 9953

BCLllA-4483 + GGGAGAGAAGAAAGGGG 17 9954

BCLllA-4407 + GAGCAGGAGAGAAGGGG 17 9955

BCLllA-9661 + GAAAGGGGUGGCAGGGG 17 9956

BCLllA-4593 + AGGGGCGGGCCGAGGGG 17 9957

BCLllA-4467 + GGCCCCCGGGGGAGGGG 17 9958 BCLllA-5413 + CAUGGUGGGCUGCGGGG 17 9959

BCLllA-9662 + CAAUGGCCAGUGCGGGG 17 9960

BCLllA-9663 + GAGGGGGAGGUGCGGGG 17 9961

BCLllA-9664 + CCAGUGCGGGGAGGGGG 17 9962

BCLllA-4395 + GACGCGGCCCCCGGGGG 17 9963

BCLllA-9665 + GGGAGGAAAGGGUGGGG 17 9964

BCLllA-9666 + UGGGAGGAAAGGGUGGG 17 9965

BCLllA-9667 + GGGGUGGCAGGGGUGGG 17 9966

BCLllA-9668 - GAGUCCGCGUGUGUGGG 17 9967

BCLllA-5414 + CUUGCGGCGAGACAUGG 17 9968

BCLllA-9669 + GUGGGAGGAAAGGGUGG 17 9969

BCLllA-9670 - AGAGUCCGCGUGUGUGG 17 9970

BCLllA-9671 + UGGUUCCAGAUGGGAUG 17 9971

BCLllA-9672 + GAGGGGAGGGGGCGCUG 17 9972

BCLllA-9673 - CGCCGCGGCGCUCGCUG 17 9973

BCLllA-5422 + CGAGACAUGGUGGGCUG 17 9974

BCLllA-9674 + AG C U G C A AG U U C A AG U G 17 9975

BCLllA-9675 + CAAGCCAAUGGCCAGUG 17 9976

BCLllA-9676 + GCGGGGAGGGGGAGGUG 17 9977

BCLllA-9677 + GGUGGGAGGAAAGGGUG 17 9978

BCLllA-9678 - U UUAGAGUCCGCGUGUG 17 9979

BCLllA-9679 + GCAGGGAAGAUGAAUUG 17 9980

BCLllA-5426 + GGGGUUUGCCUUGCUUG 17 9981

BCLllA-9680 + AGAGACACACAAAACAU 17 9982

BCLllA-9681 - CCCUGAUGUGUGUCCAU 17 9983

BCLllA-5431 + AUUAUUAUUACUAUUAU 17 9984

BCLllA-9682 - CCAGCGCCCCCUCCCCU 17 9985

BCLllA-9683 + CGAGGGGAGGGGGCGCU 17 9986

BCLllA-9684 + UCUUUUACCUCGACUCU 17 9987

BCLllA-9685 + GGGUGGGAGGAAAGGGU 17 9988

BCLllA-9686 + AAAGGGGUGGCAGGGGU 17 9989

BCLllA-9687 - U UAGAGUCCGCGUGUGU 17 9990

BCLllA-9688 + CAGGGAAGAUGAAUUGU 17 9991

BCLllA-5439 + U UAUUAUUACUAUUAU U 17 9992

BCLllA-9689 - U UAUUUCUAAUUUAU UU 17 9993

BCLllA-9690 + AGAGAGAGAGAUGAAAAAAA 20 9994

BCLllA-5443 - AACCCCAGCACUUAAGCAAA 20 9995

BCLllA-9691 - AAUUUAUUUUGGAUGUCAAA 20 9996

BCLllA-9692 + GUGGCAGGGGUGGGAGGAAA 20 9997

BCLllA-9693 - GUCGAGGUAAAAGAGAUAAA 20 9998

BCLllA-9694 + UAAAAU U AAAU AAAAU U AAA 20 9999

BCLllA-9695 + GAAGGGGAAGCUCACACCAA 20 10000 BCLllA-4541 + AAGAGACCAGGACAAGCCAA 20 10001

BCLllA-9696 + CAAAAGUGCAUACACGGCAA 20 10002

BCLllA-9697 + GCGUGGCCGGGAGAGAAGAA 20 10003

BCLllA-4422 + GCAGGGCGAGCAGGAGAGAA 20 10004

BCLllA-9698 + GGUGGCAGGGGUGGGAGGAA 20 10005

BCLllA-4404 + GAGAGAAGGGGAGGAGGGAA 20 10006

BCLllA-9699 - AGUCGAGGUAAAAGAGAUAA 20 10007

BCLllA-4455 + GGACAGAGACACACAAAACA 20 10008

BCLllA-9700 + CUGUCUCAAAAGUGCAUACA 20 10009

BCLllA-9701 - CGCGUGUGUGGGGGGGAGCA 20 10010

BCLllA-9702 + AAUAAUACAAAGAUGGCGCA 20 10011

BCLllA-9703 + AGACACACAAAACAUGGGCA 20 10012

BCLllA-9704 + G AG AG A AG A A AG G G G U G G C A 20 10013

BCLllA-9705 - GCACU UGAACUUGCAGCUCA 20 10014

BCLllA-9706 + GAAUUGUGGGAGAGCCGUCA 20 10015

BCLllA-4527 + AAAAAAAAAAAAAAAAAAGA 20 10016

BCLllA-9707 + AAU U AG AAA U A A U AC A A AG A 20 10017

BCLllA-9708 + GGAGAGCCGGGUUAGAAAGA 20 10018

BCLllA-4464 + GGCAGGGCGAGCAGGAGAGA 20 10019

BCLllA-4418 - GCAAAAGCGAGGGGGAGAGA 20 10020

BCLllA-9709 + AGAGAGAGAAGAGAGAUAGA 20 10021

BCLllA-4673 + CGGCGGCGGCGGGCGGACGA 20 10022

BCLllA-4648 + CCGGGGGAGGGGCGGGCCGA 20 10023

BCLllA-9710 - AGGACUAGAAGCAAAAGCGA 20 10024

BCLllA-4584 + AGCAGGAGAGAAGGGGAGGA 20 10025

BCLllA-4459 + GGAGAGAAGGGGAGGAGGGA 20 10026

BCLllA-4461 + GGAGGGGCGGGCCGAGGGGA 20 10027

BCLllA-4624 + CAGACGCGGCCCCCGGGGGA 20 10028

BCLllA-9711 + U UGAACGUCAGGAGUCUGGA 20 10029

BCLllA-9712 - UGCU UAAAAAAAAGCCAUGA 20 10030

BCLllA-5458 - ACCCCAGCACUUAAGCAAAC 20 10031

BCLllA-9713 - GCGGCGCUCGCUGCGGCCAC 20 10032

BCLllA-9714 - GCACCUCCCCCUCCCCGCAC 20 10033

BCLllA-9715 + CUGGACAUGAAAAAGAGACC 20 10034

BCLllA-4456 + GGACGCCAGACGCGGCCCCC 20 10035

BCLllA-9716 - CCUCGGCCCGCCCCUCCCCC 20 10036

BCLllA-4362 + CGGACGCCAGACGCGGCCCC 20 10037

BCLllA-9717 - CCCUCGGCCCGCCCCUCCCC 20 10038

BCLllA-9718 + GCCGCGGCGGUGGCGUGGCC 20 10039

BCLllA-9719 - GCCACCCCUUUCUUCUCUCC 20 10040

BCLllA-9720 - CACUGGCCAU UGGCU UGUCC 20 10041

BCLllA-9721 + AAAACAUGGGCAGGGCGAGC 20 10042 BCLllA-9722 + GGAGGGGGCGCUGGGGCCGC 20 10043

BCLllA-4490 + GGGCCGAGGGGAGGGGGCGC 20 10044

BCLllA-4442 + GCGGCGGCGGCGGCGGCGGC 20 10045

BCLllA-9723 + AAUGGACACACAUCAGGGGC 20 10046

BCLllA-4439 + GCGGCCCCCGGGGGAGGGGC 20 10047

BCLllA-5465 + GACAUGGUGGGCUGCGGGGC 20 10048

BCLllA-9724 + GGGAGGGGGAGGUGCGGGGC 20 10049

BCLllA-9725 + CGCCGCGGCGGUGGCGUGGC 20 10050

BCLllA-9726 + GGAGAGAAGAAAGGGGUGGC 20 10051

BCLllA-5468 + GGCGAGACAUGGUGGGCUGC 20 10052

BCLllA-9727 + GACAAGCCAAUGGCCAGUGC 20 10053

BCLllA-9728 + GUGCGGGGAGGGGGAGGUGC 20 10054

BCLllA-9729 + CACACCAAUGGACACACAUC 20 10055

BCLllA-9730 - GAAAAAACCCUCAUCCCAUC 20 10056

BCLllA-9731 - ACUGAUGAAGAUAUUU UCUC 20 10057

BCLllA-9732 + GAACUUGAACGUCAGGAGUC 20 10058

BCLllA-9733 - CCUCCCCCGGGGGCCGCGUC 20 10059

BCLllA-4526 + AAAAAAAAAAAAAAAAAAAG 20 10060

BCLllA-9734 + GUGGCCGGGAGAGAAGAAAG 20 10061

BCLllA-4629 + CAGGGCGAGCAGGAGAGAAG 20 10062

BCLllA-4577 + AGAGAAGGGGAGGAGGGAAG 20 10063

BCLllA-9735 + UGGGGCCGCGGGCUCACCAG 20 10064

BCLllA-9736 + AGAGAAGAAAGGGGUGGCAG 20 10065

BCLllA-9737 + CACCAAUGGACACACAUCAG 20 10066

BCLllA-9738 - CACUUGAACUUGCAGCUCAG 20 10067

BCLllA-4611 - CAAAAGCGAGGGGGAGAGAG 20 10068

BCLllA-4583 - AGCAAAAGCGAGGGGGAGAG 20 10069

BCLllA-4677 + CGGGGGAGGGGCGGGCCGAG 20 10070

BCLllA-9739 - GGACUAGAAGCAAAAGCGAG 20 10071

BCLllA-4411 + GAGGGGCGGGCCGAGGGGAG 20 10072

BCLllA-4575 + AGACGCGGCCCCCGGGGGAG 20 10073

BCLllA-9740 + GAGAGAGAGAAGAGAGAUAG 20 10074

BCLllA-9741 + CCUGCUCCCCCCCACACACG 20 10075

BCLllA-9742 + GGCUCCGCGGACGCCAGACG 20 10076

BCLllA-9743 - CUCGGCCCGCCCCUCCCCCG 20 10077

BCLllA-9744 - UCCCGGCCACGCCACCGCCG 20 10078

BCLllA-9745 + AGUGGCCGCAGCGAGCGCCG 20 10079

BCLllA-4642 + CCCGGGGGAGGGGCGGGCCG 20 10080

BCLllA-9746 + GGGAGGGGGCGCUGGGGCCG 20 10081

BCLllA-9747 + GUGCGGGGCGGGGGGCUCCG 20 10082

BCLllA-9748 - CAGGACUAGAAGCAAAAGCG 20 10083

BCLllA-9749 + GGAGGGGGAGGUGCGGGGCG 20 10084 BCLllA-9750 + CGAGCGCCGCGGCGGUGGCG 20 10085

BCLllA-9751 + ACAAGCCAAUGGCCAGUGCG 20 10086

BCLllA-9752 + UGCGGGGAGGGGGAGGUGCG 20 10087

BCLllA-9753 - CG AG G U A A A AG AG A U A A AG G 20 10088

BCLllA-9754 - ACUUGAACUUGCAGCUCAGG 20 10089

BCLllA-9755 - GACUAGAAGCAAAAGCGAGG 20 10090

BCLllA-4408 + GAGCAGGAGAGAAGGGGAGG 20 10091

BCLllA-4594 + AGGGGCGGGCCGAGGGGAGG 20 10092

BCLllA-9756 + CAAUGGCCAGUGCGGGGAGG 20 10093

BCLllA-9757 - UCGGCCCGCCCCUCCCCCGG 20 10094

BCLllA-4471 + GGCCGCAGCGAGCGCCGCGG 20 10095

BCLllA-4661 + CGCAGCGAGCGCCGCGGCGG 20 10096

BCLllA-4479 + GGCGGCGGCGGCGGCGGCGG 20 10097

BCLllA-4448 + GCGGGCGGCGGCGGCGGCGG 20 10098

BCLllA-4501 + GGGGCGGGCGGCGGCGGCGG 20 10099

BCLllA-5484 + UGCGGGGCGGGCGGCGGCGG 20 10100

BCLllA-5485 + GGCUGCGGGGCGGGCGGCGG 20 10101

BCLllA-5486 + GUGGGCUGCGGGGCGGGCGG 20 10102

BCLllA-9758 + GAGGGGGAGGUGCGGGGCGG 20 10103

BCLllA-9759 + GCAGGGGUGGGAGGAAAGGG 20 10104

BCLllA-9760 - CUUGAACUUGCAGCUCAGGG 20 10105

BCLllA-4443 + GCGGCGGCGGCGGCGGCGGG 20 10106

BCLllA-5487 + AUGGUGGGCUGCGGGGCGGG 20 10107

BCLllA-9761 + AGGGGGAGGUGCGGGGCGGG 20 10108

BCLllA-4434 + GCCGGGAGAGAAGAAAGGGG 20 10109

BCLllA-4476 + GGCGAGCAGGAGAGAAGGGG 20 10110

BCLllA-9762 + GAAGAAAGGGGUGGCAGGGG 20 10111

BCLllA-4486 + GGGAGGGGCGGGCCGAGGGG 20 10112

BCLllA-4666 + CGCGGCCCCCGGGGGAGGGG 20 10113

BCLllA-5489 + AGACAUGGUGGGCUGCGGGG 20 10114

BCLllA-9763 + AGCCAAUGGCCAGUGCGGGG 20 10115

BCLllA-9764 + GGGGAGGGGGAGGUGCGGGG 20 10116

BCLllA-9765 + UGGCCAGUGCGGGGAGGGGG 20 10117

BCLllA-4635 + CCAGACGCGGCCCCCGGGGG 20 10118

BCLllA-9766 + GGUGGGAGGAAAGGGUGGGG 20 10119

BCLllA-9767 + GGGUGGGAGGAAAGGGUGGG 20 10120

BCLllA-9768 + AAAGGGGUGGCAGGGGUGGG 20 10121

BCLllA-9769 - U UAGAGUCCGCGUGUGUGGG 20 10122

BCLllA-5490 + U UGCUUGCGGCGAGACAUGG 20 10123

BCLllA-9770 + GGGGUGGGAGGAAAGGGUGG 20 10124

BCLllA-9771 + GCCGAGGGGAGGGGGCGCUG 20 10125

BCLllA-9772 - CACCGCCGCGGCGCUCGCUG 20 10126 BCLllA-5497 + UCCCGUUUGCUUAAGUGCUG 20 10127

BCLllA-9773 + GGACAAGCCAAUGGCCAGUG 20 10128

BCLllA-9774 + AGUGCGGGGAGGGGGAGGUG 20 10129

BCLllA-9775 + AGGGGUGGGAGGAAAGGGUG 20 10130

BCLllA-9776 - UUUUAGAGUCCGCGUGUGUG 20 10131

BCLllA-9777 + GGCGCAGGGAAGAUGAAUUG 20 10132

BCLllA-5500 + GCUGGGGUUUGCCUUGCUUG 20 10133

BCLllA-9778 + GACAGAGACACACAAAACAU 20 10134

BCLllA-9779 - CCCCUCCCCGCACUGGCCAU 20 10135

BCLllA-9780 + ACACGGCAAUGGUUCCAGAU 20 10136

BCLllA-9781 + AUAAUUAUUAUUACUAUUAU 20 10137

BCLllA-9782 - GCCCCAGCGCCCCCUCCCCU 20 10138

BCLllA-9783 + GGCCGAGGGGAGGGGGCGCU 20 10139

BCLllA-5509 + UUCCCGUUUGCUUAAGUGCU 20 10140

BCLllA-9784 + CAGGGGUGGGAGGAAAGGGU 20 10141

BCLllA-9785 + AAGAAAGGGGUGGCAGGGGU 20 10142

BCLllA-9786 + GCGCAGGGAAGAUGAAUUGU 20 10143

BCLllA-9787 + UAAUUAUUAUUACUAUUAUU 20 10144

BCLllA-9788 - GUAUUAUUUCUAAUUUAUUU 20 10145

Table 15C provides exemplary targeting domains for knocking down the BCLl 1 A gene selected according to the third tier parameters. The targeting domains binds 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 BCLl 1 A gene (e.g., reduce or eliminate BCLl 1A gene expression, BCLl 1A protein function, or the level of BCLl 1A protein). One or more gRNA may be used to target an eiCas9 to the promoter region of the BCLl 1 A gene.

Table 15C

BCLllA-9794 - AAGUGGCACUGUGGAAA 17 10151

BCLllA-9795 + GGGCUGCGGGUCCGGAA 17 10152

BCLllA-9796 + G AAA U A A AG CG G CG G A A 17 10153

BCLllA-9797 - UGGGAGCUGGUGGGGAA 17 10154

BCLllA-9798 - AAAGUGGCACUGUGGAA 17 10155

BCLllA-9799 + GCCCGAGGGCGCCCCCA 17 10156

BCLllA-9800 + CGUCCUUCCCGGUCCCA 17 10157

BCLllA-9801 + CCCCCAAGGCCGAGCCA 17 10158

BCLllA-9802 + CCCGCGUGUGGACGCCA 17 10159

BCLllA-9597 - GUGUGUGGGGGGGAGCA 17 10160

BCLllA-9803 + AGGUGGGAGGGAGCGCA 17 10161

BCLllA-9804 - GGACACCAGCGCGCUCA 17 10162

BCLllA-9805 + CGCGCGGCCUGGAAAGA 17 10163

BCLllA-9806 - UCCGCGGAGUCGGGAGA 17 10164

BCLllA-9807 + CGCAGGCCGGGGCCCGA 17 10165

BCLllA-9808 - GAGAGGGGCCGCGGCGA 17 10166

BCLllA-9809 + AGCUCCGCAGCGGGCGA 17 10167

BCLllA-9810 - CGUGGGACCGGGAAGGA 17 10168

BCLllA-9811 - GGUGUGCGUACGGAGGA 17 10169

BCLllA-9812 + AGGGCUGCGGGUCCGGA 17 10170

BCLllA-9813 + GGGGAAGCGCGGGCGGA 17 10171

BCLllA-9814 - AAAUGGGGGGGUAGGGA 17 10172

BCLllA-9815 - GAGCCGUGGGACCGGGA 17 10173

BCLllA-9816 - CGCGGCGGCGGCGGGGA 17 10174

BCLllA-9817 + GGCGAGGGGAGGUGGGA 17 10175

BCLllA-9818 + UCCAGCCUAAGUUUGGA 17 10176

BCLllA-9819 - AAUAAUGAACAAUGCUA 17 10177

BCLllA-9820 - GGAAGUGGGUGUGCGUA 17 10178

BCLllA-9821 - AAGAAAAUGGGGGGGUA 17 10179

BCLllA-9822 + ACCCCCCCAUUUUCUUA 17 10180

BCLllA-9823 + U CAU U AU U U UG CAAAAC 17 10181

BCLllA-9824 + AUAGAGCGAGAGUGCAC 17 10182

BCLllA-9825 - GAGAAAAGAGGUGAGAC 17 10183

BCLllA-9826 - AGAGGGGCCGCGGCGAC 17 10184

BCLllA-9827 - GUGGGACCGGGAAGGAC 17 10185

BCLllA-9828 + AAGGCCGAGCCAGGGAC 17 10186

BCLllA-9829 + GCCUGGAAAGAGGGGAC 17 10187

BCLllA-9830 - GGGGAGAGCCGUGGGAC 17 10188

BCLllA-9831 - CAACUCACAUGCAAACC 17 10189

BCLllA-9832 + UAGAGCGAGAGUGCACC 17 10190

BCLllA-9833 + AGGCCGAGCCAGGGACC 17 10191

BCLllA-9834 + CCUGGAAAGAGGGGACC 17 10192 BCLllA-9835 - GGGAGAGCCGUGGGACC 17 10193

BCLllA-9836 - CCGGGAGCAACUCUACC 17 10194

BCLllA-9837 + CACCAGCUCCCACCCCC 17 10195

BCLllA-9838 + CGGGAGGCUGCAGCCCC 17 10196

BCLllA-9839 - GCUUUUACUUCGGCCCC 17 10197

BCLllA-9840 - CUGUGGAAAGGGGCCCC 17 10198

BCLllA-9841 + UCACCUCUUUUCUCCCC 17 10199

BCLllA-9842 - CCGCGCUUCCCCAGCCC 17 10200

BCLllA-9843 + CCGGGAGGCUGCAGCCC 17 10201

BCLllA-9844 - GGGGCGCCCUCGGGCCC 17 10202

BCLllA-9845 - CGCCGCCUGCCUCUCCC 17 10203

BCLllA-9846 + CUCACCUCU UUUCUCCC 17 10204

BCLllA-9847 - U CU AAAAAACG AU U CCC 17 10205

BCLllA-9848 + GCGGGCGGAGGGAAGCC 17 10206

BCLllA-9849 - CCCGCGCUUCCCCAGCC 17 10207

BCLllA-9850 + GCCCCCAAGGCCGAGCC 17 10208

BCLllA-9851 + CCCCGCGUGUGGACGCC 17 10209

BCLllA-9852 + GCGGACUCAGGAGCGCC 17 10210

BCLllA-9853 + GGCAGGCGGCGCAGGCC 17 10211

BCLllA-9854 + CAGGAGCCCGCGCGGCC 17 10212

BCLllA-9855 - CCGGGGCUGCAGCCUCC 17 10213

BCLllA-9856 - CAGGCCGCGCGGGCUCC 17 10214

BCLllA-9857 + CCAGGUAGAGUUGCUCC 17 10215

BCLllA-9858 + GCAGCGCCCAAGUCUCC 17 10216

BCLllA-9859 - UACGGAGGAGGGUGUCC 17 10217

BCLllA-9860 - GUCU AAAAAACG AUUCC 17 10218

BCLllA-9861 + GCGUCUCCCGUCCUUCC 17 10219

BCLllA-9862 - CCCGGUCCCCUCUU UCC 17 10220

BCLllA-9863 + AGUUACAGCUCCGCAGC 17 10221

BCLllA-9864 + CCGGCACAAAAGGCAGC 17 10222

BCLllA-9865 - ACGGUCAAGUGUGCAGC 17 10223

BCLllA-9866 + GGGCAAGCGCGAGGAGC 17 10224

BCLllA-9620 - CGUGUGUGGGGGGGAGC 17 10225

BCLllA-9867 - AACCUGGGGGUGGGAGC 17 10226

BCLllA-9868 - CCCUGGCGUCCACACGC 17 10227

BCLllA-9869 - UUCCCGAGCGCAGCCGC 17 10228

BCLllA-9870 + CCGGGCUGGGGAAGCGC 17 10229

BCLllA-9871 + CGCGGACUCAGGAGCGC 17 10230

BCLllA-9872 - CUCUUUCCAGGCCGCGC 17 10231

BCLllA-9873 + CUUGACCGUGAGCGCGC 17 10232

BCLllA-9874 + GGAGAGGCAGGCGGCGC 17 10233

BCLllA-9875 + AGGCAGGCGGCGCAGGC 17 10234 BCLllA-9876 + GGGGACCGGGGAGAGGC 17 10235

BCLllA-9877 - GCCCUCCAAACU UAGGC 17 10236

BCLllA-9878 - AGGACGGGAGACGCGGC 17 10237

BCLllA-9879 - GCGAGCGCGGCGGCGGC 17 10238

BCLllA-9880 + AGGCUGCAGCCCCGGGC 17 10239

BCLllA-9881 + UGCAAAACUGGCGGGGC 17 10240

BCLllA-9882 + UAUUUUGCAAAACUGGC 17 10241

BCLllA-9883 + AAACACCCACCUCUGGC 17 10242

BCLllA-9884 + UAAGUUUGGAGGGCUGC 17 10243

BCLllA-9885 + A C A A A AG GCGGCAGUGC 17 10244

BCLllA-9886 - CCCGCUGCCUUUUGUGC 17 10245

BCLllA-9887 + CCCGACUCCGCGGACUC 17 10246

BCLllA-9888 + GGACAAACACCCACCUC 17 10247

BCLllA-9889 - GCCUUGGGGGCGCCCUC 17 10248

BCLllA-9890 - UUUGCUGUCCUCUCCUC 17 10249

BCLllA-9891 + AGCCCGCGGCUGCGCUC 17 10250

BCLllA-9892 - AGCGCAGCCGCGGGCUC 17 10251

BCLllA-9893 - CCUGAGUCCGCGGAGUC 17 10252

BCLllA-9894 + UUGGAGGGCUGCGGGUC 17 10253

BCLllA-9895 - GUACGGAGGAGGGUGUC 17 10254

BCLllA-9896 - GCUCAGCUCUCAACUUC 17 10255

BCLllA-9897 - CUUGGGCGCUGCCCU UC 17 10256

BCLllA-9898 - ACUGCCGCCUU UUGUUC 17 10257

BCLllA-9899 - AUUCCCGGGGAGAAAAG 17 10258

BCLllA-9900 - CCACAAUAGUGAGAAAG 17 10259

BCLllA-9901 + GGCGGAAAGGAGGAAAG 17 10260

BCLllA-9902 + CCGCGCGGCCUGGAAAG 17 10261

BCLllA-9903 - AGUGGCACUGUGGAAAG 17 10262

BCLllA-9904 + CG A A A AG AG A A A U A A AG 17 10263

BCLllA-9905 - GCGGCGGGGAGGGGAAG 17 10264

BCLllA-9906 + CCGCGUGUGGACGCCAG 17 10265

BCLllA-9907 - CCUUU UGUUCCGGCCAG 17 10266

BCLllA-9908 + AAGUUACAGCUCCGCAG 17 10267

BCLllA-9909 + G CCGG CAC AAAAG G C AG 17 10268

BCLllA-9910 - C ACG G U CAAG U G U G C AG 17 10269

BCLllA-9911 + GCGCGGCCUGGAAAGAG 17 10270

BCLllA-9912 - CCGCGGAGUCGGGAGAG 17 10271

BCLllA-9913 + GCUCCGCAGCGGGCGAG 17 10272

BCLllA-9914 + AAACUUUGCCCGAGGAG 17 10273

BCLllA-9915 - GUCCGCGGAGUCGGGAG 17 10274

BCLllA-9916 + AAGAGGGGACCGGGGAG 17 10275

BCLllA-9917 - GCGGCGGCGGCGGGGAG 17 10276 BCLllA-9918 + GCGGGGCGGGGGGGGAG 17 10277

BCLllA-9919 + CAUUUUCUUACGGUGAG 17 10278

BCLllA-9920 + GGGAGCGCACGGCAACG 17 10279

BCLllA-9642 + GCUCCCCCCCACACACG 17 10280

BCLllA-9921 - CCCCUGGCGUCCACACG 17 10281

BCLllA-9922 - GGGAAGGACGGGAGACG 17 10282

BCLllA-9923 - GAGGGGCCGCGGCGACG 17 10283

BCLllA-9924 + CUGGAAAGAGGGGACCG 17 10284

BCLllA-9925 - CGCGCUUCCCCAGCCCG 17 10285

BCLllA-9926 + UAAAAGCCCCGAGCCCG 17 10286

BCLllA-9927 + GCGCAGGCCGGGGCCCG 17 10287

BCLllA-9928 + UCGGGAAACUUUGCCCG 17 10288

BCLllA-9929 - CUAAAAAACGAUUCCCG 17 10289

BCLllA-9930 - UUUCCCGAGCGCAGCCG 17 10290

BCLllA-9931 - GGCGACGGGGAGAGCCG 17 10291

BCLllA-9932 + CGGACUCAGGAGCGCCG 17 10292

BCLllA-9933 + GGCUCUCCCCGUCGCCG 17 10293

BCLllA-9934 + GCAGGCGGCGCAGGCCG 17 10294

BCLllA-9935 - AGUCGGGAGAGGGGCCG 17 10295

BCLllA-9936 + CCCCUCUCCCGACUCCG 17 10296

BCLllA-9937 - CGGCGCUCCUGAGUCCG 17 10297

BCLllA-9938 + CCCGGGCUGGGGAAGCG 17 10298

BCLllA-9939 - CACGCGGGGAGCGAGCG 17 10299

BCLllA-9940 - CCUGGCGUCCACACGCG 17 10300

BCLllA-9941 + GUCUCCAGGAGCCCGCG 17 10301

BCLllA-9942 - CCUCUU UCCAGGCCGCG 17 10302

BCLllA-9943 + GCGGGAGGGCAAGCGCG 17 10303

BCLllA-9944 - CGAGCGCGGCGGCGGCG 17 10304

BCLllA-9945 + CAGCUCCGCAGCGGGCG 17 10305

BCLllA-9946 + GCAAAACUGGCGGGGCG 17 10306

BCLllA-9947 + AUUUUGCAAAACUGGCG 17 10307

BCLllA-9948 - GCGCAGCCGCGGGCUCG 17 10308

BCLllA-9949 + C U G G CCG G A ACAAAAG G 17 10309

BCLllA-9950 + A U A A AG CG G CG G A A AG G 17 10310

BCLllA-9951 + GACCGGGGAGAGGCAGG 17 10311

BCLllA-9952 + GGAAAGGAGGAAAGAGG 17 10312

BCLllA-9953 - U UUGUUCCGGCCAGAGG 17 10313

BCLllA-9954 - GGGUGUGCGUACGGAGG 17 10314

BCLllA-9955 + CAGCGGGCGAGGGGAGG 17 10315

BCLllA-9956 - AGUGGGUGUGCGUACGG 17 10316

BCLllA-9957 + GGACUCAGGAGCGCCGG 17 10317

BCLllA-9958 + AAAGAGAAAUAAAGCGG 17 10318 BCLllA-9959 - GCGGGGAGCGAGCGCGG 17 10319

BCLllA-9960 - GGGAGCGAGCGCGGCGG 17 10320

BCLllA-9961 - AGCGAGCGCGGCGGCGG 17 10321

BCLllA-9962 + UGGGGAAGCGCGGGCGG 17 10322

BCLllA-9963 + CAAAACUGGCGGGGCGG 17 10323

BCLllA-9964 - AGCUGGUGGGGAAAGGG 17 10324

BCLllA-9965 - AAAAUGGGGGGGUAGGG 17 10325

BCLllA-9966 + AGCGAGAGUGCACCGGG 17 10326

BCLllA-9967 - GUCAAGUGUGCAGCGGG 17 10327

BCLllA-9968 + GGCUGGGGAAGCGCGGG 17 10328

BCLllA-9969 + AAAACUGGCGGGGCGGG 17 10329

BCLllA-9970 + CCGCAGCGGGCGAGGGG 17 10330

BCLllA-9971 - GCGCGGCGGCGGCGGGG 17 10331

BCLllA-9972 + AAACUGGCGGGGCGGGG 17 10332

BCLllA-9973 + UUGCAAAACUGGCGGGG 17 10333

BCLllA-9974 + AACUGGCGGGGCGGGGG 17 10334

BCLllA-9975 - ACAUGCAAACCUGGGGG 17 10335

BCLllA-9976 - ACCGUAAGAAAAUGGGG 17 10336

BCLllA-9548 - AGUCCGCGUGUGUGGGG 17 10337

BCLllA-9977 - C AC CG U A AG A A A A U G G G 17 10338

BCLllA-9978 + GGGCGAGGGGAGGUGGG 17 10339

BCLllA-9668 - GAGUCCGCGUGUGUGGG 17 10340

BCLllA-9979 - U C A CCG U A AG A A A A U G G 17 10341

BCLllA-9980 + UUAUUUUGCAAAACUGG 17 10342

BCLllA-9981 - CUCACAUGCAAACCUGG 17 10343

BCLllA-9982 - CUGGGGGUGGGAGCUGG 17 10344

BCLllA-9670 - AGAGUCCGCGUGUGUGG 17 10345

BCLllA-9983 - GCGGAGCUGUAACUUGG 17 10346

BCLllA-9984 - CCCUGGCUCGGCCUUGG 17 10347

BCLllA-9985 + AUCCAGCCUAAGU UUGG 17 10348

BCLllA-9986 - CUCACCGUAAGAAAAUG 17 10349

BCLllA-9987 - GUGAGAAAGUGGCACUG 17 10350

BCLllA-9988 - ACUCACAUGCAAACCUG 17 10351

BCLllA-9989 - CCUCCCCUCGCCCGCUG 17 10352

BCLllA-9990 + CUAAGUUUGGAGGGCUG 17 10353

BCLllA-9991 + GCUGCAGCCCCGGGCUG 17 10354

BCLllA-9992 + CGCUCGCUCCCCGCGUG 17 10355

BCLllA-9993 - GGGGGUGGGAGCUGGUG 17 10356

BCLllA-9678 - U UUAGAGUCCGCGUGUG 17 10357

BCLllA-9549 - UAGAGUCCGCGUGUGUG 17 10358

BCLllA-9994 + ACU UUCUCACUAUUGUG 17 10359

BCLllA-9995 + CCACUU UCUCACUAUUG 17 10360 BCLllA-9996 - UCCCUGGCUCGGCCUUG 17 10361

BCLllA-9997 - ACUCACCGUAAG A A A A U 17 10362

BCLllA-9998 - GCUGCGGAGCUGUAACU 17 10363

BCLllA-9999 - GCGGGCUCCUGGAGACU 17 10364

BCLllA-10000 - AAC U CAC AU G CAAACCU 17 10365

BCLllA-10001 - GGCCUUGGGGGCGCCCU 17 10366

BCLllA-10002 - GGUCCCUGGCUCGGCCU 17 10367

BCLllA-10003 - CUU UGCUGUCCUCUCCU 17 10368

BCLllA-10004 + GAGCCCGCGGCUGCGCU 17 10369

BCLllA-10005 + GGCUGCAGCCCCGGGCU 17 10370

BCLllA-10006 - GAGCGCAGCCGCGGGCU 17 10371

BCLllA-10007 - CGGCGGGGAGGGGAAGU 17 10372

BCLllA-10008 - UCCUGAGUCCGCGGAGU 17 10373

BCLllA-10009 + AUUUUCUUACGGUGAGU 17 10374

BCLllA-10010 - GCGACGGGGAGAGCCGU 17 10375

BCLllA-10011 - U UGUUCCGGCCAGAGGU 17 10376

BCLllA-10012 + AGCGGGCGAGGGGAGGU 17 10377

BCLllA-10013 - UAAGAAAAUGGGGGGGU 17 10378

BCLllA-10014 - CAUGCAAACCUGGGGGU 17 10379

BCLllA-10015 - UGGGGGUGGGAGCUGGU 17 10380

BCLllA-9687 - U UAGAGUCCGCGUGUGU 17 10381

BCLllA-10016 + CACUUUCUCACUAUUGU 17 10382

BCLllA-10017 - CGCAGCCCUCCAAACUU 17 10383

BCLllA-10018 - GGCUCAGCUCUCAACUU 17 10384

BCLllA-10019 - CGGGCUCCUGGAGACU U 17 10385

BCLllA-10020 - GCUCGGGGCUUUUACU U 17 10386

BCLllA-10021 - GUCCCUGGCUCGGCCUU 17 10387

BCLllA-10022 + GGAAUCCAGCCUAAGUU 17 10388

BCLllA-10023 - GAGGUGAGACUGGCU UU 17 10389

BCLllA-10024 - U CCCACU CACCG U AAG AAAA 20 10390

BCLllA-10025 + CCACCUCUGGCCGGAACAAA 20 10391

BCLllA-10026 + GCGCGAGGAGCCGGCACAAA 20 10392

BCLllA-10027 - CUU UAUUUCUCUUU UCGAAA 20 10393

BCLllA-10028 - GGUGGGAGCUGGUGGGGAAA 20 10394

BCLllA-10029 - AGAAAGUGGCACUGUGGAAA 20 10395

BCLllA-10030 + GGAGGGCUGCGGGUCCGGAA 20 10396

BCLllA-10031 + AGAGAAAUAAAGCGGCGGAA 20 10397

BCLllA-10032 - GGGUGGGAGCUGGUGGGGAA 20 10398

BCLllA-10033 - GAGAAAGUGGCACUGUGGAA 20 10399

BCLllA-10034 + GGGGCCCGAGGGCGCCCCCA 20 10400

BCLllA-10035 + UCCCGUCCUUCCCGGUCCCA 20 10401

BCLllA-10036 + GCGCCCCCAAGGCCGAGCCA 20 10402 BCLllA-10037 + CUCCCCGCGUGUGGACGCCA 20 10403

BCLllA-9701 - CGCGUGUGUGGGGGGGAGCA 20 10404

BCLllA-10038 + GGGAGGUGGGAGGGAGCGCA 20 10405

BCLllA-10039 - U UUGGACACCAGCGCGCUCA 20 10406

BCLllA-10040 + GCCCGCGCGGCCUGGAAAGA 20 10407

BCLllA-10041 - GAGUCCGCGGAGUCGGGAGA 20 10408

BCLllA-10042 + CGGCGCAGGCCGGGGCCCGA 20 10409

BCLllA-10043 - CGGGAGAGGGGCCGCGGCGA 20 10410

BCLllA-10044 + UACAGCUCCGCAGCGGGCGA 20 10411

BCLllA-10045 - AGCCGUGGGACCGGGAAGGA 20 10412

BCLllA-10046 - GUGGGUGUGCGUACGGAGGA 20 10413

BCLllA-10047 + UGGAGGGCUGCGGGUCCGGA 20 10414

BCLllA-10048 + GCUGGGGAAGCGCGGGCGGA 20 10415

BCLllA-10049 - AGAAAAUGGGGGGGUAGGGA 20 10416

BCLllA-10050 - GGAGAGCCGUGGGACCGGGA 20 10417

BCLllA-10051 - GAGCGCGGCGGCGGCGGGGA 20 10418

BCLllA-10052 + GCGGGCGAGGGGAGGUGGGA 20 10419

BCLllA-10053 + GAAUCCAGCCUAAGUUUGGA 20 10420

BCLllA-10054 - CAAAAUAAUGAACAAUGCUA 20 10421

BCLllA-10055 - AGGGGAAGUGGGUGUGCGUA 20 10422

BCLllA-10056 - CGUAAGAAAAUGGGGGGGUA 20 10423

BCLllA-10057 + CCUACCCCCCCAUUUUCUUA 20 10424

BCLllA-10058 + UGUUCAUUAUUUUGCAAAAC 20 10425

BCLllA-10059 + AAAAUAGAGCGAGAGUGCAC 20 10426

BCLllA-10060 - GGGGAGAAAAGAGGUGAGAC 20 10427

BCLllA-10061 - GGGAGAGGGGCCGCGGCGAC 20 10428

BCLllA-10062 - GCCGUGGGACCGGGAAGGAC 20 10429

BCLllA-10063 + CCCAAGGCCGAGCCAGGGAC 20 10430

BCLllA-10064 + GCGGCCUGGAAAGAGGGGAC 20 10431

BCLllA-10065 - GACGGGGAGAGCCGUGGGAC 20 10432

BCLllA-10066 - GAACAACUCACAUGCAAACC 20 10433

BCLllA-10067 + AAAUAGAGCGAGAGUGCACC 20 10434

BCLllA-10068 + CCAAGGCCGAGCCAGGGACC 20 10435

BCLllA-10069 + CGGCCUGGAAAGAGGGGACC 20 10436

BCLllA-10070 - ACGGGGAGAGCCGUGGGACC 20 10437

BCLllA-10071 - UGUCCGGGAGCAACUCUACC 20 10438

BCLllA-10072 + CCCCACCAGCUCCCACCCCC 20 10439

BCLllA-10073 + CACCGGGAGGCUGCAGCCCC 20 10440

BCLllA-10074 - GGGGCU UUUACUUCGGCCCC 20 10441

BCLllA-10075 - GCACUGUGGAAAGGGGCCCC 20 10442

BCLllA-10076 + GUCUCACCUCUU UUCUCCCC 20 10443

BCLllA-10077 - CGCCCGCGCU UCCCCAGCCC 20 10444 BCLllA-10078 + GCACCGGGAGGCUGCAGCCC 20 10445

BCLllA-10079 - U UGGGGGCGCCCUCGGGCCC 20 10446

BCLllA-10080 - CUGCGCCGCCUGCCUCUCCC 20 10447

BCLllA-10081 + AGUCUCACCUCUUU UCUCCC 20 10448

BCLllA-10082 - AAGUCUAAAAAACGAUUCCC 20 10449

BCLllA-10083 + AGCGCGGGCGGAGGGAAGCC 20 10450

BCLllA-10084 - CCGCCCGCGCUUCCCCAGCC 20 10451

BCLllA-10085 + GGCGCCCCCAAGGCCGAGCC 20 10452

BCLllA-10086 + GCUCCCCGCGUGUGGACGCC 20 10453

BCLllA-10087 + UCCGCGGACUCAGGAGCGCC 20 10454

BCLllA-10088 + AGAGGCAGGCGGCGCAGGCC 20 10455

BCLllA-10089 + CUCCAGGAGCCCGCGCGGCC 20 10456

BCLllA-10090 - AGCCCGGGGCUGCAGCCUCC 20 10457

BCLllA-10091 - U UCCAGGCCGCGCGGGCUCC 20 10458

BCLllA-10092 + AAGCCAGGUAGAGUUGCUCC 20 10459

BCLllA-10093 + AGGGCAGCGCCCAAGUCUCC 20 10460

BCLllA-10094 - GCGUACGGAGGAGGGUGUCC 20 10461

BCLllA-10095 - CAAGUCUAAAAAACGAUUCC 20 10462

BCLllA-10096 + GCCGCGUCUCCCGUCCU UCC 20 10463

BCLllA-10097 - CUCCCCGGUCCCCUCUUUCC 20 10464

BCLllA-10098 + CCAAG U UACAGCU CCG CAGC 20 10465

BCLllA-10099 + GAGCCGGCA C A A A AG G C AG C 20 10466

BCLllA-10100 - CUCACGGUCAAGUGUGCAGC 20 10467

BCLllA-10101 + GGAGGGCAAGCGCGAGGAGC 20 10468

BCLllA-9563 - CCGCGUGUGUGGGGGGGAGC 20 10469

BCLllA-10102 - GCAAACCUGGGGGUGGGAGC 20 10470

BCLllA-10103 - GGCCCCUGGCGUCCACACGC 20 10471

BCLllA-10104 - AGUUUCCCGAGCGCAGCCGC 20 10472

BCLllA-10105 + GCCCCGGGCUGGGGAAGCGC 20 10473

BCLllA-10106 + CUCCGCGGACUCAGGAGCGC 20 10474

BCLllA-10107 - CCCCUCUUUCCAGGCCGCGC 20 10475

BCLllA-10108 + ACACUUGACCGUGAGCGCGC 20 10476

BCLllA-10109 + CGGGGAGAGGCAGGCGGCGC 20 10477

BCLllA-10110 + GAGAGGCAGGCGGCGCAGGC 20 10478

BCLllA-10111 + AGAGGGGACCGGGGAGAGGC 20 10479

BCLllA-10112 - GCAGCCCUCCAAACUUAGGC 20 10480

BCLllA-10113 - GGAAGGACGGGAGACGCGGC 20 10481

BCLllA-10114 - GGAGCGAGCGCGGCGGCGGC 20 10482

BCLllA-10115 + GGGAGGCUGCAGCCCCGGGC 20 10483

BCLllA-10116 + U UUUGCAAAACUGGCGGGGC 20 10484

BCLllA-10117 + CAUUAUUUUGCAAAACUGGC 20 10485

BCLllA-10118 + GACAAACACCCACCUCUGGC 20 10486 BCLllA-10119 + GCCUAAGUUUGGAGGGCUGC 20 10487

BCLllA-10120 + GGAACAAAAGGCGGCAGUGC 20 10488

BCLllA-10121 - UGUCCCGCUGCCU UUUGUGC 20 10489

BCLllA-10122 + UCUCCCGACUCCGCGGACUC 20 10490

BCLllA-10123 + GCGGGACAAACACCCACCUC 20 10491

BCLllA-10124 - UCGGCCUUGGGGGCGCCCUC 20 10492

BCLllA-10125 - UUCUUUGCUGUCCUCUCCUC 20 10493

BCLllA-10126 + CCGAGCCCGCGGCUGCGCUC 20 10494

BCLllA-10127 - CCGAGCGCAGCCGCGGGCUC 20 10495

BCLllA-10128 - GCUCCUGAGUCCGCGGAGUC 20 10496

BCLllA-10129 + AGUUUGGAGGGCUGCGGGUC 20 10497

BCLllA-10130 - UGCGUACGGAGGAGGGUGUC 20 10498

BCLllA-10131 - GAGGCUCAGCUCUCAACUUC 20 10499

BCLllA-10132 - AGACUUGGGCGCUGCCCUUC 20 10500

BCLllA-10133 - GGCACUGCCGCCUU UUGUUC 20 10501

BCLllA-10134 - ACGAUUCCCGGGGAGAAAAG 20 10502

BCLllA-10135 - UCCCCACAAUAGUGAGAAAG 20 10503

BCLllA-10136 + AGCGGCGGAAAGGAGGAAAG 20 10504

BCLllA-10137 + AGCCCGCGCGGCCUGGAAAG 20 10505

BCLllA-10138 - GAAAGUGGCACUGUGGAAAG 20 10506

BCLllA-10139 + U U U CG A A A AG AG AAA U A A AG 20 10507

BCLllA-10140 - GCGGCGGCGGGGAGGGGAAG 20 10508

BCLllA-10141 + UCCCCGCGUGUGGACGCCAG 20 10509

BCLllA-10142 - CCGCCUUUUGUUCCGGCCAG 20 10510

BCLllA-10143 + UCCAAGUUACAGCUCCGCAG 20 10511

BCLllA-10144 + GGAGCCGGCA C A A A AG G C AG 20 10512

BCLllA-10145 - GCUCACGGUCAAGUGUGCAG 20 10513

BCLllA-10146 + CCCGCGCGGCCUGGAAAGAG 20 10514

BCLllA-10147 - AGUCCGCGGAGUCGGGAGAG 20 10515

BCLllA-10148 + ACAGCUCCGCAGCGGGCGAG 20 10516

BCLllA-10149 + GGGAAACUUUGCCCGAGGAG 20 10517

BCLllA-10150 - UGAGUCCGCGGAGUCGGGAG 20 10518

BCLllA-10151 + GGAAAGAGGGGACCGGGGAG 20 10519

BCLllA-10152 - AGCGCGGCGGCGGCGGGGAG 20 10520

BCLllA-10153 + CUGGCGGGGCGGGGGGGGAG 20 10521

BCLllA-10154 + CCCCAUU UUCUUACGGUGAG 20 10522

BCLllA-10155 + GGAGGGAGCGCACGGCAACG 20 10523

BCLllA-9741 + CCUGCUCCCCCCCACACACG 20 10524

BCLllA-10156 - CGGCCCCUGGCGUCCACACG 20 10525

BCLllA-10157 - ACCGGGAAGGACGGGAGACG 20 10526

BCLllA-10158 - GGAGAGGGGCCGCGGCGACG 20 10527

BCLllA-10159 + GGCCUGGAAAGAGGGGACCG 20 10528 BCLllA-10160 - GCCCGCGCUUCCCCAGCCCG 20 10529

BCLllA-10161 + AAGUAAAAGCCCCGAGCCCG 20 10530

BCLllA-10162 + GCGGCGCAGGCCGGGGCCCG 20 10531

BCLllA-10163 + CGCUCGGGAAACUUUGCCCG 20 10532

BCLllA-10164 - AGUCUAAAAAACGAUUCCCG 20 10533

BCLllA-10165 - AAGUUUCCCGAGCGCAGCCG 20 10534

BCLllA-10166 - CGCGGCGACGGGGAGAGCCG 20 10535

BCLllA-10167 + CCGCGGACUCAGGAGCGCCG 20 10536

BCLllA-10168 + CACGGCUCUCCCCGUCGCCG 20 10537

BCLllA-10169 + GAGGCAGGCGGCGCAGGCCG 20 10538

BCLllA-10170 - CGGAGUCGGGAGAGGGGCCG 20 10539

BCLllA-10171 + CGGCCCCUCUCCCGACUCCG 20 10540

BCLllA-10172 - CCCCGGCGCUCCUGAGUCCG 20 10541

BCLllA-10173 + AGCCCCGGGCUGGGGAAGCG 20 10542

BCLllA-10174 - CCACACGCGGGGAGCGAGCG 20 10543

BCLllA-10175 - GCCCCUGGCGUCCACACGCG 20 10544

BCLllA-10176 + CAAGUCUCCAGGAGCCCGCG 20 10545

BCLllA-10177 - UCCCCUCUUUCCAGGCCGCG 20 10546

BCLllA-10178 + GGCGCGGGAGGGCAAGCGCG 20 10547

BCLllA-10179 - GAGCGAGCGCGGCGGCGGCG 20 10548

BCLllA-10180 + UUACAGCUCCGCAGCGGGCG 20 10549

BCLllA-10181 + U UUGCAAAACUGGCGGGGCG 20 10550

BCLllA-10182 + AUUAUUUUGCAAAACUGGCG 20 10551

BCLllA-10183 - CGAGCGCAGCCGCGGGCUCG 20 10552

BCLllA-10184 + CCUCUGGCCGGAACAAAAGG 20 10553

BCLllA-10185 + G AAA U A A AG CG G CG G A A AG G 20 10554

BCLllA-10186 + GGGGACCGGGGAGAGGCAGG 20 10555

BCLllA-10187 + GGCGGAAAGGAGGAAAGAGG 20 10556

BCLllA-10188 - CCUU UUGUUCCGGCCAGAGG 20 10557

BCLllA-10189 - AGUGGGUGUGCGUACGGAGG 20 10558

BCLllA-10190 + CCGCAGCGGGCGAGGGGAGG 20 10559

BCLllA-10191 - GGAAGUGGGUGUGCGUACGG 20 10560

BCLllA-10192 + CGCGGACUCAGGAGCGCCGG 20 10561

BCLllA-10193 + CGAAAAGAGAAAUAAAGCGG 20 10562

BCLllA-10194 - CACGCGGGGAGCGAGCGCGG 20 10563

BCLllA-10195 - GCGGGGAGCGAGCGCGGCGG 20 10564

BCLllA-10196 - GGGAGCGAGCGCGGCGGCGG 20 10565

BCLllA-10197 + GGCUGGGGAAGCGCGGGCGG 20 10566

BCLllA-10198 + UUGCAAAACUGGCGGGGCGG 20 10567

BCLllA-10199 - GGGAGCUGGUGGGGAAAGGG 20 10568

BCLllA-10200 - AAGAAAAUGGGGGGGUAGGG 20 10569

BCLllA-10201 + UAGAGCGAGAGUGCACCGGG 20 10570 BCLllA-10202 - ACGGUCAAGUGUGCAGCGGG 20 10571

BCLllA-10203 + CCGGGCUGGGGAAGCGCGGG 20 10572

BCLllA-10204 + UGCAAAACUGGCGGGGCGGG 20 10573

BCLllA-10205 + GCUCCGCAGCGGGCGAGGGG 20 10574

BCLllA-10206 - CGAGCGCGGCGGCGGCGGGG 20 10575

BCLllA-10207 + GCAAAACUGGCGGGGCGGGG 20 10576

BCLllA-10208 + AUUUUGCAAAACUGGCGGGG 20 10577

BCLllA-10209 + CAAAACUGGCGGGGCGGGGG 20 10578

BCLllA-10210 - CUCACAUGCAAACCUGGGGG 20 10579

BCLllA-10211 - CUCACCGUAAGAAAAUGGGG 20 10580

BCLllA-9577 - UAGAGUCCGCGUGUGUGGGG 20 10581

BCLllA-10212 - ACUCACCGUAAGAAAAUGGG 20 10582

BCLllA-10213 + AGCGGGCGAGGGGAGGUGGG 20 10583

BCLllA-9769 - U UAGAGUCCGCGUGUGUGGG 20 10584

BCLllA-10214 - CACUCACCGUAAGAAAAUGG 20 10585

BCLllA-10215 + UCAUUAUUUUGCAAAACUGG 20 10586

BCLllA-10216 - CAACUCACAUGCAAACCUGG 20 10587

BCLllA-10217 - AACCUGGGGGUGGGAGCUGG 20 10588

BCLllA-9578 - UUUAGAGUCCGCGUGUGUGG 20 10589

BCLllA-10218 - GCUGCGGAGCUGUAACU UGG 20 10590

BCLllA-10219 - GGUCCCUGGCUCGGCCU UGG 20 10591

BCLllA-10220 + GGAAUCCAGCCUAAGU UUGG 20 10592

BCLllA-10221 - CCACUCACCGUAAGAAAAUG 20 10593

BCLllA-10222 - AUAGUGAGAAAGUGGCACUG 20 10594

BCLllA-10223 - ACAACUCACAUGCAAACCUG 20 10595

BCLllA-10224 - CCACCUCCCCUCGCCCGCUG 20 10596

BCLllA-10225 + AGCCUAAGUUUGGAGGGCUG 20 10597

BCLllA-10226 + GAGGCUGCAGCCCCGGGCUG 20 10598

BCLllA-10227 + CCGCGCUCGCUCCCCGCGUG 20 10599

BCLllA-10228 - CCUGGGGGUGGGAGCUGGUG 20 10600

BCLllA-9581 - CAUUUUAGAGUCCGCGUGUG 20 10601

BCLllA-9776 - U UUUAGAGUCCGCGUGUGUG 20 10602

BCLllA-10229 + GCCACU UUCUCACUAUUGUG 20 10603

BCLllA-10230 + GUGCCACU UUCUCACUAUUG 20 10604

BCLllA-10231 - CGGUCCCUGGCUCGGCCUUG 20 10605

BCLllA-10232 - CCCACU CACCG UAAGAAAAU 20 10606

BCLllA-10233 - CCCGCUGCGGAGCUGUAACU 20 10607

BCLllA-10234 - CGCGCGGGCUCCUGGAGACU 20 10608

BCLllA-10235 - AACAACUCACAUGCAAACCU 20 10609

BCLllA-10236 - CUCGGCCUUGGGGGCGCCCU 20 10610

BCLllA-10237 - CCCGGUCCCUGGCUCGGCCU 20 10611

BCLllA-10238 - UUUCUUUGCUGUCCUCUCCU 20 10612 BCLllA-10239 + CCCGAGCCCGCGGCUGCGCU 20 10613

BCLllA-10240 + GGAGGCUGCAGCCCCGGGCU 20 10614

BCLllA-10241 - CCCGAGCGCAGCCGCGGGCU 20 10615

BCLllA-10242 - CGGCGGCGGGGAGGGGAAGU 20 10616

BCLllA-10243 - CGCUCCUGAGUCCGCGGAGU 20 10617

BCLllA-10244 + CCCAUU UUCUUACGGUGAGU 20 10618

BCLllA-10245 - GCGGCGACGGGGAGAGCCGU 20 10619

BCLllA-10246 - CUU UUGUUCCGGCCAGAGGU 20 10620

BCLllA-10247 + CGCAGCGGGCGAGGGGAGGU 20 10621

BCLllA-10248 - CCGUAAGAAAAUGGGGGGGU 20 10622

BCLllA-10249 - UCACAUGCAAACCUGGGGGU 20 10623

BCLllA-10250 - ACCUGGGGGUGGGAGCUGGU 20 10624

BCLllA-9586 - AUUUUAGAGUCCGCGUGUGU 20 10625

BCLllA-10251 + UGCCACUU UCUCACUAUUGU 20 10626

BCLllA-10252 - ACCCGCAGCCCUCCAAACU U 20 10627

BCLllA-10253 - GGAGGCUCAGCUCUCAACUU 20 10628

BCLllA-10254 - GCGCGGGCUCCUGGAGACUU 20 10629

BCLllA-10255 - CGGGCUCGGGGCU UUUACUU 20 10630

BCLllA-10256 - CCGGUCCCUGGCUCGGCCUU 20 10631

BCLllA-10257 + CGCGGAAUCCAGCCUAAGUU 20 10632

BCLllA-10258 - AAAGAGGUGAGACUGGCUUU 20 10633

Table 16A provides exemplary targeting domains for knocking down the BCLl 1 A 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) and have a high level of

orthogonality, and the 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 BCLl 1 A gene (e.g., reduce or eliminate BCLl 1 A gene expression, BCLl 1 A protein function, or the level of BCLl 1A protein). One or more gRNA may be used to target an eiCas9 to the promoter region of the BCLl 1 A gene.

Table 16A

BCLllA-10261 + GUGGCGUGGCCGGGAGAGAAGAA 23 10636

BCLllA-10262 + GGUGGCGUGGCCGGGAGAGAAGAA 24 10637

BCLllA-10263 + CACGGCAAUGGUUCCAGA 18 10638

BCLllA-10264 + ACACGGCAAUGGUUCCAGA 19 10639

BCLllA-9557 + UACACGGCAAUGGUUCCAGA 20 10640

BCLllA-10265 + AUACACGGCAAUGGUUCCAGA 21 10641

BCLllA-10266 + CAUACACGGCAAUGGUUCCAGA 22 10642

BCLllA-10267 + GCAUACACGGCAAUGGUUCCAGA 23 10643

BCLllA-10268 + UGCAUACACGGCAAUGGUUCCAGA 24 10644

BCLllA-6258 + UUAUUGGGUUACU UACGC 18 10645

BCLllA-6259 + AUUAUUGGGUUACUUACGC 19 10646

BCLllA-6260 + UAUUAUUGGGUUACUUACGC 20 10647

BCLllA-6261 + CUAUUAUUGGGUUACU UACGC 21 10648

BCLllA-6262 + ACUAUUAUUGGGUUACUUACGC 22 10649

BCLllA-6263 + UACUAUUAUUGGGU UACUUACGC 23 10650

BCLllA-6264 + U UACUAUUAUUGGGUUACUUACGC 24 10651

BCLllA-10269 + GGGAGAGAAGAAAGGGGUGGC 21 10652

BCLllA-10270 + CGGGAGAGAAGAAAGGGGUGGC 22 10653

BCLllA-10271 + CCGGGAGAGAAGAAAGGGGUGGC 23 10654

BCLllA-10272 + GCCGGGAGAGAAGAAAGGGGUGGC 24 10655

BCLllA-6265 + UCCCGUU UGCUUAAGUGC 18 10656

BCLllA-6266 + UUCCCGU UUGCUUAAGUGC 19 10657

BCLllA-5352 + AUUCCCGUUUGCU UAAGUGC 20 10658

BCLllA-6267 + AAUUCCCGUU UGCUUAAGUGC 21 10659

BCLllA-6268 + GAAUUCCCGU UUGCUUAAGUGC 22 10660

BCLllA-6269 + AGAAUUCCCGUU UGCUUAAGUGC 23 10661

BCLllA-6270 + GAGAAUUCCCGU UUGCUUAAGUGC 24 10662

BCLllA-10273 + CCUGCGAACUUGAACGUC 18 10663

BCLllA-10274 + CCCUGCGAACUUGAACGUC 19 10664

BCLllA-9570 + UCCCUGCGAACUUGAACGUC 20 10665

BCLllA-10275 + GUCCCUGCGAACUUGAACGUC 21 10666

BCLllA-10276 + CGUCCCUGCGAACU UGAACGUC 22 10667

BCLllA-10277 + ACGUCCCUGCGAACUUGAACGUC 23 10668

BCLllA-10278 + GACGUCCCUGCGAACUUGAACGUC 24 10669

BCLllA-10279 + UACAAAGAUGGCGCAGGGAAG 21 10670

BCLllA-10280 + A U AC A A AG AUGGCGCAGGGAAG 22 10671

BCLllA-10281 + AAUACAAAGAUGGCGCAGGGAAG 23 10672

BCLllA-10282 + UAAUACAAAGAUGGCGCAGGGAAG 24 10673

BCLllA-10283 + CGGU UCACAUCGGGAGAG 18 10674

BCLllA-10284 + UCGGUUCACAUCGGGAGAG 19 10675

BCLllA-10285 + CUCGGUUCACAUCGGGAGAG 20 10676

BCLllA-10286 + GCUCGGUUCACAUCGGGAGAG 21 10677 BCLllA-10287 + GGCUCGGU UCACAUCGGGAGAG 22 10678

BCLllA-10288 + CGGCUCGGUUCACAUCGGGAGAG 23 10679

BCLllA-10289 + ACGGCUCGGUUCACAUCGGGAGAG 24 10680

BCLllA-10290 + AAUGGUUCCAGAUGGGAU 18 10681

BCLllA-10291 + CAAUGGUUCCAGAUGGGAU 19 10682

BCLllA-10292 + GCAAUGGUUCCAGAUGGGAU 20 10683

BCLllA-10293 + GGCAAUGGUUCCAGAUGGGAU 21 10684

BCLllA-10294 + CGGCAAUGGUUCCAGAUGGGAU 22 10685

BCLllA-10295 + ACGGCAAUGGUUCCAGAUGGGAU 23 10686

BCLllA-10296 + CACGGCAAUGGUUCCAGAUGGGAU 24 10687

BCLllA-10297 + AACUUGAACGUCAGGAGU 18 10688

BCLllA-10298 + GAACUUGAACGUCAGGAGU 19 10689

BCLllA-10299 + CGAACUUGAACGUCAGGAGU 20 10690

BCLllA-10300 + GCGAACUUGAACGUCAGGAGU 21 10691

BCLllA-10301 + UGCGAACUUGAACGUCAGGAGU 22 10692

BCLllA-10302 + CUGCGAACUUGAACGUCAGGAGU 23 10693

BCLllA-10303 + CCUGCGAACUUGAACGUCAGGAGU 24 10694

BCLllA-6304 - AACCCCAGCACU UAAGCAAAC 21 10695

BCLllA-6305 - AAACCCCAGCACUUAAGCAAAC 22 10696

BCLllA-6306 - CAAACCCCAGCACUUAAGCAAAC 23 10697

BCLllA-6307 - GCAAACCCCAGCACUUAAGCAAAC 24 10698

BCLllA-10304 - AAGCAAAAGCGAGGGGGAGAG 21 10699

BCLllA-10305 - GAAGCAAAAGCGAGGGGGAGAG 22 10700

BCLllA-10306 - AGAAGCAAAAGCGAGGGGGAGAG 23 10701

BCLllA-10307 - UAGAAGCAAAAGCGAGGGGGAGAG 24 10702

Table 16B provides exemplary targeting domains for knocking down the BCLl 1 A 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 the 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 BCLl 1 A gene (e.g., reduce or eliminate BCLl 1 A gene expression, BCLl 1A protein function, or the level of BCLl 1A protein). One or more gRNA may be used to target an eiCas9 to the promoter region of the BCLl 1A gene.

Table 16B

Strand Length NO

BCLllA-10308 + GUGGCCGGGAGAGAAGAA 18 10703

BCLllA-10309 + CGUGGCCGGGAGAGAAGAA 19 10704

BCLllA-9697 + GCGUGGCCGGGAGAGAAGAA 20 10705

BCLllA-10310 + GUGGCAGGGGUGGGAGGA 18 10706

BCLllA-10311 + GGUGGCAGGGGUGGGAGGA 19 10707

BCLllA-10312 + GGGUGGCAGGGGUGGGAGGA 20 10708

BCLllA-10313 + GGGGUGGCAGGGGUGGGAGGA 21 10709

BCLllA-10314 + AGGGGUGGCAGGGGUGGGAGGA 22 10710

BCLllA-10315 + AAGGGGUGGCAGGGGUGGGAGGA 23 10711

BCLllA-10316 + AAAGGGGUGGCAGGGGUGGGAGGA 24 10712

BCLllA-10317 + UAAUUAUUAUUACUAUUA 18 10713

BCLllA-10318 + AUAAUUAUUAUUACUAUUA 19 10714

BCLllA-10319 + AAUAAUUAUUAUUACUAUUA 20 10715

BCLllA-10320 + UAAUAAUUAUUAUUACUAUUA 21 10716

BCLllA-10321 + UUAAUAAUUAUUAUUACUAUUA 22 10717

BCLllA-10322 + AUUAAUAAUUAUUAUUACUAUUA 23 10718

BCLllA-10323 + UAUUAAUAAUUAUUAUUACUAUUA 24 10719

BCLllA-10324 + AGAGAAGAAAGGGGUGGC 18 10720

BCLllA-10325 + GAGAGAAGAAAGGGGUGGC 19 10721

BCLllA-9726 + GGAGAGAAGAAAGGGGUGGC 20 10722

BCLllA-10326 + AAAGAUGGCGCAGGGAAG 18 10723

BCLllA-10327 + CAAAGAUGGCGCAGGGAAG 19 10724

BCLllA-10328 + ACAAAGAUGGCGCAGGGAAG 20 10725

BCLllA-6350 - CCCAGCACUUAAGCAAAC 18 10726

BCLllA-6351 - CCCCAGCACUUAAGCAAAC 19 10727

BCLllA-5458 - ACCCCAGCACUUAAGCAAAC 20 10728

BCLllA-10329 - UUCACGAGAAAAACCUCC 18 10729

BCLllA-10330 - U U U CACG AG AAAAACCU CC 19 10730

BCLllA-10331 - UUUUCACGAGAAAAACCUCC 20 10731

BCLllA-10332 - UUUUUCACGAGAAAAACCUCC 21 10732

BCLllA-10333 - AUUUUUCACGAGAAAAACCUCC 22 10733

BCLllA-10334 - AAU U U U U CACG AG AAAAACCU CC 23 10734

BCLllA-10335 - AAAU U U U U CACG AG AAAAACCU CC 24 10735

BCLllA-10336 - UGAUGAAGAUAUUUUCUC 18 10736

BCLllA-10337 - CUGAUGAAGAUAUUUUCUC 19 10737

BCLllA-9731 - ACUGAUGAAGAUAUUUUCUC 20 10738

BCLllA-10338 - CACUGAUGAAGAUAUUUUCUC 21 10739

BCLllA-10339 - GCACUGAUGAAGAUAUUUUCUC 22 10740

BCLllA-10340 - GGCACUGAUGAAGAUAUUUUCUC 23 10741

BCLllA-10341 - AGGCACUGAUGAAGAUAUUUUCUC 24 10742 BCLllA-10342 - CAAAAGCGAGGGGGAGAG 18 10743

BCLllA-10343 - GCAAAAGCGAGGGGGAGAG 19 10744

BCLllA-4583 - AGCAAAAGCGAGGGGGAGAG 20 10745

BCLllA-10344 - UAUUAUUUCUAAUUUAUU 18 10746

BCLllA-10345 - GUAUUAUUUCUAAUU UAUU 19 10747

BCLllA-10346 - UGUAUUAUUUCUAAU UUAUU 20 10748

BCLllA-10347 - U UGUAUUAUUUCUAAU UUAUU 21 10749

BCLllA-10348 - U UUGUAUUAUUUCUAAUUUAUU 22 10750

BCLllA-10349 - CUUUGUAUUAUUUCUAAUUUAUU 23 10751

BCLllA-10350 - UCUUUGUAUUAUUUCUAAUUUAUU 24 10752

BCLllA-10351 - UUGAAUAAUCUUUCAUUU 18 10753

BCLllA-10352 - UUUGAAUAAUCUUUCAUUU 19 10754

BCLllA-10353 - U UUUGAAUAAUCUUUCAUUU 20 10755

BCLllA-10354 - U UUUUGAAUAAUCUUUCAUUU 21 10756

BCLllA-10355 - U UUUUUGAAUAAUCUU UCAUUU 22 10757

BCLllA-10356 - CUU UUUUGAAUAAUCU UUCAUUU 23 10758

BCLllA-10357 - UCU UUUUUGAAUAAUCUUUCAUUU 24 10759

Table 16C provides exemplary targeting domains for knocking down the BCLl 1 A 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 the 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 BCLl 1 A gene (e.g., reduce or eliminate BCLl 1 A gene expression, BCLl 1A protein function, or the level of BCLl 1A protein). One or more gRNA may be used. Table 16C

BCLllA-10365 + UCAGGGGCUGGACAUGAAA 19 10768

BCLllA-10366 + AUCAGGGGCUGGACAUGAAA 20 10769

BCLllA-10367 + CAUCAGGGGCUGGACAUGAAA 21 10770

BCLllA-10368 + ACAUCAGGGGCUGGACAUGAAA 22 10771

BCLllA-10369 + CA CAUCAGGGGCUGGACAUGAAA 23 10772

BCLllA-10370 + ACACAUCAGGGGCUGGACAUGAAA 24 10773

BCLllA-10371 + ACACACGCGGACUCUAAA 18 10774

BCLllA-10372 + CACACACGCGGACUCUAAA 19 10775

BCLllA-10373 + CCACACACGCGGACUCUAAA 20 10776

BCLllA-10374 + CCCACACACGCGGACUCUAAA 21 10777

BCLllA-10375 + CCCCACACACGCGGACUCUAAA 22 10778

BCLllA-10376 + CCCCCACACACGCGGACUCUAAA 23 10779

BCLllA-10377 + CCCCCCACACACGCGGACUCUAAA 24 10780

BCLllA-10378 + AGAGGGAGAGAGAGAGAA 18 10781

BCLllA-10379 + AAGAGGGAGAGAGAGAGAA 19 10782

BCLllA-4921 + AAAGAGGGAGAGAGAGAGAA 20 10783

BCLllA-10380 + AAAAGAGGGAGAGAGAGAGAA 21 10784

BCLllA-10381 + AAAAAGAGGGAGAGAGAGAGAA 22 10785

BCLllA-10382 + AAAAAAGAGGGAGAGAGAGAGAA 23 10786

BCLllA-10383 + AAAAAAAGAGGGAGAGAGAGAGAA 24 10787

BCLllA-10384 + AGGGCGAGCAGGAGAGAA 18 10788

BCLllA-10385 + CAGGGCGAGCAGGAGAGAA 19 10789

BCLllA-4422 + GCAGGGCGAGCAGGAGAGAA 20 10790

BCLllA-10386 + GGCAGGGCGAGCAGGAGAGAA 21 10791

BCLllA-10387 + GGGCAGGGCGAGCAGGAGAGAA 22 10792

BCLllA-10388 + UGGGCAGGGCGAGCAGGAGAGAA 23 10793

BCLllA-10389 + AUGGGCAGGGCGAGCAGGAGAGAA 24 10794

BCLllA-10390 + GAGAAGGGGAGGAGGGAA 18 10795

BCLllA-10391 + AGAGAAGGGGAGGAGGGAA 19 10796

BCLllA-4404 + GAGAGAAGGGGAGGAGGGAA 20 10797

BCLllA-10392 + GGAGAGAAGGGGAGGAGGGAA 21 10798

BCLllA-10393 + AGGAGAGAAGGGGAGGAGGGAA 22 10799

BCLllA-10394 + CAGGAGAGAAGGGGAGGAGGGAA 23 10800

BCLllA-10395 + GCAGGAGAGAAGGGGAGGAGGGAA 24 10801

BCLllA-10396 + ACGACGGCUCGGUUCACA 18 10802

BCLllA-10397 + GACGACGGCUCGGUUCACA 19 10803

BCLllA-10398 + GGACGACGGCUCGGUUCACA 20 10804

BCLllA-10399 + CGGACGACGGCUCGGUUCACA 21 10805

BCLllA-10400 + GCGGACGACGGCUCGGUUCACA 22 10806

BCLllA-10401 + GGCGGACGACGGCUCGGUUCACA 23 10807

BCLllA-10402 + GGGCGGACGACGGCUCGGUUCACA 24 10808

BCLllA-10403 + AAGGGGAAGCUCACACCA 18 10809 BCLllA-10404 + GAAGGGGAAGCUCACACCA 19 10810

BCLllA-10405 + GGAAGGGGAAGCUCACACCA 20 10811

BCLllA-10406 + GGGAAGGGGAAGCUCACACCA 21 10812

BCLllA-10407 + AGGGAAGGGGAAGCUCACACCA 22 10813

BCLllA-10408 + GAGGGAAGGGGAAGCUCACACCA 23 10814

BCLllA-10409 + GGAGGGAAGGGGAAGCUCACACCA 24 10815

BCLllA-10410 + AGAAAGAAGGAGACUCCA 18 10816

BCLllA-10411 + UAGAAAGAAGGAGACUCCA 19 10817

BCLllA-10412 + U UAGAAAGAAGGAGACUCCA 20 10818

BCLllA-10413 + G U U AG AAAG AAGG AG ACU CCA 21 10819

BCLllA-10414 + GGUUAGAAAGAAGGAGACUCCA 22 10820

BCLllA-10415 + GGGUUAGAAAGAAGGAGACUCCA 23 10821

BCLllA-10416 + CGGGUUAGAAAGAAGGAGACUCCA 24 10822

BCLllA-10417 + GGCUCACCAGUGGCCGCA 18 10823

BCLllA-10418 + GGGCUCACCAGUGGCCGCA 19 10824

BCLllA-10419 + CGGGCUCACCAGUGGCCGCA 20 10825

BCLllA-10420 + GCGGGCUCACCAGUGGCCGCA 21 10826

BCLllA-10421 + CGCGGGCUCACCAGUGGCCGCA 22 10827

BCLllA-10422 + CCGCGGGCUCACCAGUGGCCGCA 23 10828

BCLllA-10423 + GCCGCGGGCUCACCAGUGGCCGCA 24 10829

BCLllA-10424 + UAAUACAAAGAUGGCGCA 18 10830

BCLllA-10425 + AUAAUACAAAGAUGGCGCA 19 10831

BCLllA-9702 + AAUAAUACAAAGAUGGCGCA 20 10832

BCLllA-10426 + A A A U A A U AC A A AG A U G G CG C A 21 10833

BCLllA-10427 + GAAAUAAUACAAAGAUGGCGCA 22 10834

BCLllA-10428 + AG AAA U A A U AC A A AG A U G G CG C A 23 10835

BCLllA-10429 + UAGAAAUAAUACAAAGAUGGCGCA 24 10836

BCLllA-10430 + AAAAAAAAAAAAAAAAGA 18 10837

BCLllA-10431 + AAAAAAAAAAAAAAAAAGA 19 10838

BCLllA-4527 + A A A A A A A A A A A A A A A AAAG A 20 10839

BCLllA-10432 + AAAAAAAAAAAAAAAAAAAGA 21 10840

BCLllA-10433 + A A A A A A A A A A A A A A A A AAA AG A 22 10841

BCLllA-10434 + A A A A A A A A A A A A A A A A AAA A AG A 23 10842

BCLllA-10435 + AAAAAAAAAAAAAAAAAAAAAAGA 24 10843

BCLllA-10436 + AGAGCCGGGUUAGAAAGA 18 10844

BCLllA-10437 + GAGAGCCGGGUUAGAAAGA 19 10845

BCLllA-9708 + GGAGAGCCGGGUUAGAAAGA 20 10846

BCLllA-10438 + GGGAGAGCCGGGUUAGAAAGA 21 10847

BCLllA-10439 + CGGGAGAGCCGGGUUAGAAAGA 22 10848

BCLllA-10440 + U CGGG AG AG CCGGGU U AG AAAG A 23 10849

BCLllA-10441 + AUCGGGAGAGCCGGGU UAGAAAGA 24 10850

BCLllA-10442 + CGUGGCCGGGAGAGAAGA 18 10851 BCLllA-10443 + GCGUGGCCGGGAGAGAAGA 19 10852

BCLllA-10444 + GGCGUGGCCGGGAGAGAAGA 20 10853

BCLllA-10445 + UGGCGUGGCCGGGAGAGAAGA 21 10854

BCLllA-10446 + GUGGCGUGGCCGGGAGAGAAGA 22 10855

BCLllA-10447 + GGUGGCGUGGCCGGGAGAGAAGA 23 10856

BCLllA-10448 + CGGUGGCGUGGCCGGGAGAGAAGA 24 10857

BCLllA-10449 + AGAGAGAGAGAAGAGAGA 18 10858

BCLllA-10450 + GAGAGAGAGAGAAGAGAGA 19 10859

BCLllA-4845 + GGAGAGAGAGAGAAGAGAGA 20 10860

BCLllA-10451 + GGGAGAGAGAGAGAAGAGAGA 21 10861

BCLllA-10452 + AGGGAGAGAGAGAGAAGAGAGA 22 10862

BCLllA-10453 + GAGGGAGAGAGAGAGAAGAGAGA 23 10863

BCLllA-10454 + AGAGGGAGAGAGAGAGAAGAGAGA 24 10864

BCLllA-10455 + UAGAGGGAGAGAGAGAGA 18 10865

BCLllA-10456 + AUAGAGGGAGAGAGAGAGA 19 10866

BCLllA-10457 + GAUAGAGGGAGAGAGAGAGA 20 10867

BCLllA-10458 + AGAUAGAGGGAGAGAGAGAGA 21 10868

BCLllA-10459 + GAGAUAGAGGGAGAGAGAGAGA 22 10869

BCLllA-10460 + AGAGAUAGAGGGAGAGAGAGAGA 23 10870

BCLllA-10461 + GAGAGAUAGAGGGAGAGAGAGAGA 24 10871

BCLllA-10462 + GAUAGAGGGAGAGAGAGA 18 10872

BCLllA-10463 + AGAUAGAGGGAGAGAGAGA 19 10873

BCLllA-10464 + GAGAUAGAGGGAGAGAGAGA 20 10874

BCLllA-10465 + AGAGAUAGAGGGAGAGAGAGA 21 10875

BCLllA-10466 + GAGAGAUAGAGGGAGAGAGAGA 22 10876

BCLllA-10467 + AGAGAGAUAGAGGGAGAGAGAGA 23 10877

BCLllA-10468 + AAGAGAGAUAGAGGGAGAGAGAGA 24 10878

BCLllA-10469 + AAAAAAGAGGGAGAGAGA 18 10879

BCLllA-10470 + AAAAAAAGAGGGAGAGAGA 19 10880

BCLllA-4911 + AAAAAAAAGAGGGAGAGAGA 20 10881

BCLllA-10471 + A A A A A A A A AG AGGGAGAGAGA 21 10882

BCLllA-10472 + AAAAAAAAAAGAGGGAGAGAGA 22 10883

BCLllA-10473 + AAAAAAAAAAAGAGGGAGAGAGA 23 10884

BCLllA-10474 + A A A A A A AAA A AAG AGGGAGAGAGA 24 10885

BCLllA-10475 + GAGAUAGAGGGAGAGAGA 18 10886

BCLllA-10476 + AGAGAUAGAGGGAGAGAGA 19 10887

BCLllA-10477 + GAGAGAUAGAGGGAGAGAGA 20 10888

BCLllA-10478 + AGAGAGAUAGAGGGAGAGAGA 21 10889

BCLllA-10479 + AAGAGAGAUAGAGGGAGAGAGA 22 10890

BCLllA-10480 + GAAGAGAGAUAGAGGGAGAGAGA 23 10891

BCLllA-10481 + AGAAGAGAGAUAGAGGGAGAGAGA 24 10892

BCLllA-10482 + CAGGGCGAGCAGGAGAGA 18 10893 BCLllA-10483 + GCAGGGCGAGCAGGAGAGA 19 10894

BCLllA-4464 + GGCAGGGCGAGCAGGAGAGA 20 10895

BCLllA-10484 + GGGCAGGGCGAGCAGGAGAGA 21 10896

BCLllA-10485 + UGGGCAGGGCGAGCAGGAGAGA 22 10897

BCLllA-10486 + AUGGGCAGGGCGAGCAGGAGAGA 23 10898

BCLllA-10487 + CAUGGGCAGGGCGAGCAGGAGAGA 24 10899

BCLllA-10488 + AAAAAAAAGAGGGAGAGA 18 10900

BCLllA-10489 + A A A A A A A A AG AGGGAGAGA 19 10901

BCLllA-4909 + AAAAAAAAAAGAGGGAGAGA 20 10902

BCLllA-10490 + A A A A A A A A A A AG AG G G AG AG A 21 10903

BCLllA-10491 + A A A A A A AAA A AAG AGGGAGAGA 22 10904

BCLllA-10492 + A A A A A A A A A AAA AG AGGGAGAGA 23 10905

BCLllA-10493 + AAAAAAAAAAAAAAGAGGGAGAGA 24 10906

BCLllA-10494 + GAGAGAUAGAGGGAGAGA 18 10907

BCLllA-10495 + AGAGAGAUAGAGGGAGAGA 19 10908

BCLllA-10496 + AAGAGAGAUAGAGGGAGAGA 20 10909

BCLllA-10497 + GAAGAGAGAUAGAGGGAGAGA 21 10910

BCLllA-10498 + AGAAGAGAGAUAGAGGGAGAGA 22 10911

BCLllA-10499 + GAGAAGAGAGAUAGAGGGAGAGA 23 10912

BCLllA-10500 + AGAGAAGAGAGAUAGAGGGAGAGA 24 10913

BCLllA-10501 + AAAAAAAAAAGAGGGAGA 18 10914

BCLllA-10502 + AAAAAAAAAAAGAGGGAGA 19 10915

BCLllA-4907 + AAAAAAAAAAAAGAGGGAGA 20 10916

BCLllA-10503 + A A A A A A A A A AAA AG AG G G AG A 21 10917

BCLllA-10504 + AAAAAAAAAAAAAAGAGGGAGA 22 10918

BCLllA-10505 + A A A A A A A A A A AAA A AG AG G G AG A 23 10919

BCLllA-10506 + AAAAAAAAAAAAAAAAGAGGGAGA 24 10920

BCLllA-10507 + AAGAGAGAUAGAGGGAGA 18 10921

BCLllA-10508 + GAAGAGAGAUAGAGGGAGA 19 10922

BCLllA-10509 + AGAAGAGAGAUAGAGGGAGA 20 10923

BCLllA-10510 + GAGAAGAGAGAUAGAGGGAGA 21 10924

BCLllA-10511 + AGAGAAGAGAGAUAGAGGGAGA 22 10925

BCLllA-10512 + GAGAGAAGAGAGAUAGAGGGAGA 23 10926

BCLllA-10513 + AGAGAGAAGAGAGAUAGAGGGAGA 24 10927

BCLllA-10514 + AGAGAGAAGAGAGAUAGA 18 10928

BCLllA-10515 + GAGAGAGAAGAGAGAUAGA 19 10929

BCLllA-9709 + AGAGAGAGAAGAGAGAUAGA 20 10930

BCLllA-10516 + GAGAGAGAGAAGAGAGAUAGA 21 10931

BCLllA-10517 + AGAGAGAGAGAAGAGAGAUAGA 22 10932

BCLllA-10518 + GAGAGAGAGAGAAGAGAGAUAGA 23 10933

BCLllA-10519 + GGAGAGAGAGAGAAGAGAGAUAGA 24 10934

BCLllA-10520 + CGGGAGAGCCGGGUUAGA 18 10935 BCLllA-10521 + UCGGGAGAGCCGGGUUAGA 19 10936

BCLllA-10522 + AUCGGGAGAGCCGGGUUAGA 20 10937

BCLllA-10523 + CAUCGGGAGAGCCGGGUUAGA 21 10938

BCLllA-10524 + ACAUCGGGAGAGCCGGGUUAGA 22 10939

BCLllA-10525 + CACAUCGGGAGAGCCGGGUUAGA 23 10940

BCLllA-10526 + UCACAUCGGGAGAGCCGGGUUAGA 24 10941

BCLllA-10527 + GGGGGAGGGGCGGGCCGA 18 10942

BCLllA-10528 + CGGGGGAGGGGCGGGCCGA 19 10943

BCLllA-4648 + CCGGGGGAGGGGCGGGCCGA 20 10944

BCLllA-10529 + CCCGGGGGAGGGGCGGGCCGA 21 10945

BCLllA-10530 + CCCCGGGGGAGGGGCGGGCCGA 22 10946

BCLllA-10531 + CCCCCGGGGGAGGGGCGGGCCGA 23 10947

BCLllA-10532 + GCCCCCGGGGGAGGGGCGGGCCGA 24 10948

BCLllA-10533 + UGGGCAGGGCGAGCAGGA 18 10949

BCLllA-10534 + AUGGGCAGGGCGAGCAGGA 19 10950

BCLllA-10535 + CAUGGGCAGGGCGAGCAGGA 20 10951

BCLllA-10536 + ACAUGGGCAGGGCGAGCAGGA 21 10952

BCLllA-10537 + AACAUGGGCAGGGCGAGCAGGA 22 10953

BCLllA-10538 + AAACAUGGGCAGGGCGAGCAGGA 23 10954

BCLllA-10539 + AAAACAUGGGCAGGGCGAGCAGGA 24 10955

BCLllA-10540 + CAGGAGAGAAGGGGAGGA 18 10956

BCLllA-10541 + GCAGGAGAGAAGGGGAGGA 19 10957

BCLllA-4584 + AGCAGGAGAGAAGGGGAGGA 20 10958

BCLllA-10542 + GAGCAGGAGAGAAGGGGAGGA 21 10959

BCLllA-10543 + CGAGCAGGAGAGAAGGGGAGGA 22 10960

BCLllA-10544 + GCGAGCAGGAGAGAAGGGGAGGA 23 10961

BCLllA-10545 + GGCGAGCAGGAGAGAAGGGGAGGA 24 10962

BCLllA-10546 + A A A A A A A A A A A AG AG G G A 18 10963

BCLllA-10547 + AAAAAAAAAAAAAGAGGGA 19 10964

BCLllA-4905 + A A A A A A A A A A AAA AG AG G G A 20 10965

BCLllA-10548 + AAAAAAAAAAAAAAAGAGGGA 21 10966

BCLllA-10549 + A A A A A A A A A A AAA A A AG AG G G A 22 10967

BCLllA-10550 + AAAAAAAAAAAAAAAAAGAGGGA 23 10968

BCLllA-10551 + A A A A A A A A A A AAA A A A A AG AG G G A 24 10969

BCLllA-10552 + AGAAGAGAGAUAGAGGGA 18 10970

BCLllA-10553 + GAGAAGAGAGAUAGAGGGA 19 10971

BCLllA-10554 + AGAGAAGAGAGAUAGAGGGA 20 10972

BCLllA-10555 + GAGAGAAGAGAGAUAGAGGGA 21 10973

BCLllA-10556 + AGAGAGAAGAGAGAUAGAGGGA 22 10974

BCLllA-10557 + GAGAGAGAAGAGAGAUAGAGGGA 23 10975

BCLllA-10558 + AGAGAGAGAAGAGAGAUAGAGGGA 24 10976

BCLllA-10559 + AGAGAAGGGGAGGAGGGA 18 10977 BCLllA-10560 + GAGAGAAGGGGAGGAGGGA 19 10978

BCLllA-4459 + GGAGAGAAGGGGAGGAGGGA 20 10979

BCLllA-10561 + AGGAGAGAAGGGGAGGAGGGA 21 10980

BCLllA-10562 + CAGGAGAGAAGGGGAGGAGGGA 22 10981

BCLllA-10563 + GCAGGAGAGAAGGGGAGGAGGGA 23 10982

BCLllA-10564 + AGCAGGAGAGAAGGGGAGGAGGGA 24 10983

BCLllA-10565 + GCGGUGGCGUGGCCGGGA 18 10984

BCLllA-10566 + GGCGGUGGCGUGGCCGGGA 19 10985

BCLllA-10567 + CGGCGGUGGCGUGGCCGGGA 20 10986

BCLllA-10568 + GCGGCGGUGGCGUGGCCGGGA 21 10987

BCLllA-10569 + CGCGGCGGUGGCGUGGCCGGGA 22 10988

BCLllA-10570 + CCGCGGCGGUGGCGUGGCCGGGA 23 10989

BCLllA-10571 + GCCGCGGCGGUGGCGUGGCCGGGA 24 10990

BCLllA-10572 + AGGGGCGGGCCGAGGGGA 18 10991

BCLllA-10573 + GAGGGGCGGGCCGAGGGGA 19 10992

BCLllA-4461 + GGAGGGGCGGGCCGAGGGGA 20 10993

BCLllA-10574 + GGGAGGGGCGGGCCGAGGGGA 21 10994

BCLllA-10575 + GGGGAGGGGCGGGCCGAGGGGA 22 10995

BCLllA-10576 + GGGGGAGGGGCGGGCCGAGGGGA 23 10996

BCLllA-10577 + CGGGGGAGGGGCGGGCCGAGGGGA 24 10997

BCLllA-10578 + CAAUGGCCAGUGCGGGGA 18 10998

BCLllA-10579 + CCAAUGGCCAGUGCGGGGA 19 10999

BCLllA-9558 + GCCAAUGGCCAGUGCGGGGA 20 11000

BCLllA-10580 + AGCCAAUGGCCAGUGCGGGGA 21 11001

BCLllA-10581 + AAGCCAAUGGCCAGUGCGGGGA 22 11002

BCLllA-10582 + CAAGCCAAUGGCCAGUGCGGGGA 23 11003

BCLllA-10583 + ACAAGCCAAUGGCCAGUGCGGGGA 24 11004

BCLllA-10584 + GUCAGGAGUCUGGAUGGA 18 11005

BCLllA-10585 + CGUCAGGAGUCUGGAUGGA 19 11006

BCLllA-10586 + ACGUCAGGAGUCUGGAUGGA 20 11007

BCLllA-10587 + AACGUCAGGAGUCUGGAUGGA 21 11008

BCLllA-10588 + GAACGUCAGGAGUCUGGAUGGA 22 11009

BCLllA-10589 + UGAACGUCAGGAGUCUGGAUGGA 23 11010

BCLllA-10590 + UUGAACGUCAGGAGUCUGGAUGGA 24 11011

BCLllA-10591 + AGAGAGAGAAGAGAGAUA 18 11012

BCLllA-10592 + GAGAGAGAGAAGAGAGAUA 19 11013

BCLllA-10593 + AGAGAGAGAGAAGAGAGAUA 20 11014

BCLllA-10594 + GAGAGAGAGAGAAGAGAGAUA 21 11015

BCLllA-10595 + GGAGAGAGAGAGAAGAGAGAUA 22 11016

BCLllA-10596 + GGGAGAGAGAGAGAAGAGAGAUA 23 11017

BCLllA-10597 + AGGGAGAGAGAGAGAAGAGAGAUA 24 11018

BCLllA-10598 + GACAGAGACACACAAAAC 18 11019 BCLllA-10599 + GGACAGAGACACACAAAAC 19 11020

BCLllA-10600 + UGGACAGAGACACACAAAAC 20 11021

BCLllA-10601 + AUGGACAGAGACACACAAAAC 21 11022

BCLllA-10602 + GAUGGACAGAGACACACAAAAC 22 11023

BCLllA-10603 + GGAUGGACAGAGACACACAAAAC 23 11024

BCLllA-10604 + UGGAUGGACAGAGACACACAAAAC 24 11025

BCLllA-10605 + CGUGACGUCCCUGCGAAC 18 11026

BCLllA-10606 + ACGUGACGUCCCUGCGAAC 19 11027

BCLllA-10607 + GACGUGACGUCCCUGCGAAC 20 11028

BCLllA-10608 + GGACGUGACGUCCCUGCGAAC 21 11029

BCLllA-10609 + CGGACGUGACGUCCCUGCGAAC 22 11030

BCLllA-10610 + GCGGACGUGACGUCCCUGCGAAC 23 11031

BCLllA-10611 + UGCGGACGUGACGUCCCUGCGAAC 24 11032

BCLllA-10612 + CUGCUCCCCCCCACACAC 18 11033

BCLllA-10613 + CCUGCUCCCCCCCACACAC 19 11034

BCLllA-10614 + CCCUGCUCCCCCCCACACAC 20 11035

BCLllA-10615 + GCCCUGCUCCCCCCCACACAC 21 11036

BCLllA-10616 + CGCCCUGCUCCCCCCCACACAC 22 11037

BCLllA-10617 + GCGCCCUGCUCCCCCCCACACAC 23 11038

BCLllA-10618 + UGCGCCCUGCUCCCCCCCACACAC 24 11039

BCLllA-10619 + UGGACAUGAAAAAGAGAC 18 11040

BCLllA-10620 + CUGGACAUGAAAAAGAGAC 19 11041

BCLllA-10621 + GCUGGACAUGAAAAAGAGAC 20 11042

BCLllA-10622 + GGCUGGACAUGAAAAAGAGAC 21 11043

BCLllA-10623 + GGGCUGGACAUGAAAAAGAGAC 22 11044

BCLllA-10624 + GGGGCUGGACAUGAAAAAGAGAC 23 11045

BCLllA-10625 + AGGGGCUGGACAUGAAAAAGAGAC 24 11046

BCLllA-10626 + ACACAUCAGGGGCUGGAC 18 11047

BCLllA-10627 + CACACAUCAGGGGCUGGAC 19 11048

BCLllA-10628 + ACACACAUCAGGGGCUGGAC 20 11049

BCLllA-10629 + GACACACAUCAGGGGCUGGAC 21 11050

BCLllA-10630 + GGACACACAUCAGGGGCUGGAC 22 11051

BCLllA-10631 + UGGACACACAUCAGGGGCUGGAC 23 11052

BCLllA-10632 + AUGGACACACAUCAGGGGCUGGAC 24 11053

BCLllA-6411 + UAUUAUUGGGUUACUUAC 18 11054

BCLllA-6412 + CUAUUAUUGGGUUACUUAC 19 11055

BCLllA-6413 + ACUAUUAUUGGGUUACUUAC 20 11056

BCLllA-6414 + UACUAUUAUUGGGU UACUUAC 21 11057

BCLllA-6415 + U UACUAUUAUUGGGUUACUUAC 22 11058

BCLllA-6416 + AUUACUAUUAUUGGGUUACUUAC 23 11059

BCLllA-6417 + UAUUACUAUUAUUGGGUUACUUAC 24 11060

BCLllA-10633 + A A A A U G G C A A A AG C CC C C 18 11061 BCLllA-10634 + A A A A A U G G C A A A AG C CC C C 19 11062

BCLllA-10635 + AAAAAAUGGCAAAAGCCCCC 20 11063

BCLllA-10636 + AAAAAAAUGGCAAAAGCCCCC 21 11064

BCLllA-10637 + GAAAAAAAUGGCAAAAGCCCCC 22 11065

BCLllA-10638 + UGAAAAAAAUGGCAAAAGCCCCC 23 11066

BCLllA-10639 + AUGAAAAAAAUGGCAAAAGCCCCC 24 11067

BCLllA-10640 + ACGCCAGACGCGGCCCCC 18 11068

BCLllA-10641 + GACGCCAGACGCGGCCCCC 19 11069

BCLllA-4456 + GGACGCCAGACGCGGCCCCC 20 11070

BCLllA-10642 + CGGACGCCAGACGCGGCCCCC 21 11071

BCLllA-10643 + GCGGACGCCAGACGCGGCCCCC 22 11072

BCLllA-10644 + CGCGGACGCCAGACGCGGCCCCC 23 11073

BCLllA-10645 + CCGCGGACGCCAGACGCGGCCCCC 24 11074

BCLllA-10646 + GACGCCAGACGCGGCCCC 18 11075

BCLllA-10647 + GGACGCCAGACGCGGCCCC 19 11076

BCLllA-4362 + CGGACGCCAGACGCGGCCCC 20 11077

BCLllA-10648 + GCGGACGCCAGACGCGGCCCC 21 11078

BCLllA-10649 + CGCGGACGCCAGACGCGGCCCC 22 11079

BCLllA-10650 + CCGCGGACGCCAGACGCGGCCCC 23 11080

BCLllA-10651 + UCCGCGGACGCCAGACGCGGCCCC 24 11081

BCLllA-10652 + GGACGCCAGACGCGGCCC 18 11082

BCLllA-10653 + CGGACGCCAGACGCGGCCC 19 11083

BCLllA-4825 + GCGGACGCCAGACGCGGCCC 20 11084

BCLllA-10654 + CG CGGACG CCAGACG CGGCCC 21 11085

BCLllA-10655 + CCGCGGACGCCAGACGCGGCCC 22 11086

BCLllA-10656 + UCCGCGGACGCCAGACGCGGCCC 23 11087

BCLllA-10657 + CUCCGCGGACGCCAGACGCGGCCC 24 11088

BCLllA-10658 + CCGGGGGAGGGGCGGGCC 18 11089

BCLllA-10659 + CCCGGGGGAGGGGCGGGCC 19 11090

BCLllA-5064 + CCCCGGGGGAGGGGCGGGCC 20 11091

BCLllA-10660 + CCCCCGGGGGAGGGGCGGGCC 21 11092

BCLllA-10661 + GCCCCCGGGGGAGGGGCGGGCC 22 11093

BCLllA-10662 + GGCCCCCGGGGGAGGGGCGGGCC 23 11094

BCLllA-10663 + CGGCCCCCGGGGGAGGGGCGGGCC 24 11095

BCLllA-10664 + GGAGGGGGCGCUGGGGCC 18 11096

BCLllA-10665 + GGGAGGGGGCGCUGGGGCC 19 11097

BCLllA-10666 + GGGGAGGGGGCGCUGGGGCC 20 11098

BCLllA-10667 + AGGGGAGGGGGCGCUGGGGCC 21 11099

BCLllA-10668 + GAGGGGAGGGGGCGCUGGGGCC 22 11100

BCLllA-10669 + CGAGGGGAGGGGGCGCUGGGGCC 23 11101

BCLllA-10670 + CCGAGGGGAGGGGGCGCUGGGGCC 24 11102

BCLllA-10671 + CGCGGCGGUGGCGUGGCC 18 11103 BCLllA-10672 + CCGCGGCGGUGGCGUGGCC 19 11104

BCLllA-9718 + GCCGCGGCGGUGGCGUGGCC 20 11105

BCLllA-10673 + CGCCGCGGCGGUGGCGUGGCC 21 11106

BCLllA-10674 + GCGCCGCGGCGGUGGCGUGGCC 22 11107

BCLllA-10675 + AGCGCCGCGGCGGUGGCGUGGCC 23 11108

BCLllA-10676 + GAGCGCCGCGGCGGUGGCGUGGCC 24 11109

BCLllA-10677 + UGCGGGGCGGGGGGCUCC 18 11110

BCLllA-10678 + GUGCGGGGCGGGGGGCUCC 19 11111

BCLllA-10679 + GGUGCGGGGCGGGGGGCUCC 20 11112

BCLllA-10680 + AGGUGCGGGGCGGGGGGCUCC 21 11113

BCLllA-10681 + GAGGUGCGGGGCGGGGGGCUCC 22 11114

BCLllA-10682 + GGAGGUGCGGGGCGGGGGGCUCC 23 11115

BCLllA-10683 + GGGAGGUGCGGGGCGGGGGGCUCC 24 11116

BCLllA-10684 + AACAUGGGCAGGGCGAGC 18 11117

BCLllA-10685 + AAACAUGGGCAGGGCGAGC 19 11118

BCLllA-9721 + AAAACAUGGGCAGGGCGAGC 20 11119

BCLllA-10686 + CAAAACAUGGGCAGGGCGAGC 21 11120

BCLllA-10687 + ACAAAACAUGGGCAGGGCGAGC 22 11121

BCLllA-10688 + CA CAAAACAUGGGCAGGGCGAGC 23 11122

BCLllA-10689 + ACACAAAACAUGGGCAGGGCGAGC 24 11123

BCLllA-10690 + GCCGAGGGGAGGGGGCGC 18 11124

BCLllA-10691 + GGCCGAGGGGAGGGGGCGC 19 11125

BCLllA-4490 + GGGCCGAGGGGAGGGGGCGC 20 11126

BCLllA-10692 + CGGGCCGAGGGGAGGGGGCGC 21 11127

BCLllA-10693 + GCGGGCCGAGGGGAGGGGGCGC 22 11128

BCLllA-10694 + GGCGGGCCGAGGGGAGGGGGCGC 23 11129

BCLllA-10695 + GGGCGGGCCGAGGGGAGGGGGCGC 24 11130

BCLllA-10696 + AUAAUACAAAGAUGGCGC 18 11131

BCLllA-10697 + AAUAAUACAAAGAUGGCGC 19 11132

BCLllA-9565 + AAAUAAUACAAAGAUGGCGC 20 11133

BCLllA-10698 + GAAAUAAUACAAAGAUGGCGC 21 11134

BCLllA-10699 + AGAAAUAAUACAAAGAUGGCGC 22 11135

BCLllA-10700 + UAGAAAUAAUACAAAGAUGGCGC 23 11136

BCLllA-10701 + U UAGAAAUAAUACAAAGAUGGCGC 24 11137

BCLllA-10702 + GAGGGGGAGGUGCGGGGC 18 11138

BCLllA-10703 + GGAGGGGGAGGUGCGGGGC 19 11139

BCLllA-9724 + GGGAGGGGGAGGUGCGGGGC 20 11140

BCLllA-10704 + GGGGAGGGGGAGGUGCGGGGC 21 11141

BCLllA-10705 + CGGGGAGGGGGAGGUGCGGGGC 22 11142

BCLllA-10706 + GCGGGGAGGGGGAGGUGCGGGGC 23 11143

BCLllA-10707 + UGCGGGGAGGGGGAGGUGCGGGGC 24 11144

BCLllA-10708 + CCGCGGCGGUGGCGUGGC 18 11145 BCLllA-10709 + GCCGCGGCGGUGGCGUGGC 19 11146

BCLllA-9725 + CGCCGCGGCGGUGGCGUGGC 20 11147

BCLllA-10710 + GCGCCGCGGCGGUGGCGUGGC 21 11148

BCLllA-10711 + AGCGCCGCGGCGGUGGCGUGGC 22 11149

BCLllA-10712 + GAGCGCCGCGGCGGUGGCGUGGC 23 11150

BCLllA-10713 + CGAGCGCCGCGGCGGUGGCGUGGC 24 11151

BCLllA-10714 + CAAGCCAAUGGCCAGUGC 18 11152

BCLllA-10715 + ACAAGCCAAUGGCCAGUGC 19 11153

BCLllA-9727 + GACAAGCCAAUGGCCAGUGC 20 11154

BCLllA-10716 + GGACAAGCCAAUGGCCAGUGC 21 11155

BCLllA-10717 + AGGACAAGCCAAUGGCCAGUGC 22 11156

BCLllA-10718 + CAGGACAAGCCAAUGGCCAGUGC 23 11157

BCLllA-10719 + C C AG G A C A AG CCAAUGGCCAGUGC 24 11158

BCLllA-10720 + CACCAAUGGACACACAUC 18 11159

BCLllA-10721 + ACACCAAUGGACACACAUC 19 11160

BCLllA-9729 + CACACCAAUGGACACACAUC 20 11161

BCLllA-10722 + UCACACCAAUGGACACACAUC 21 11162

BCLllA-10723 + CUCA CACCAAUGGACACACAUC 22 11163

BCLllA-10724 + GCUCACACCAAUGGACACACAUC 23 11164

BCLllA-10725 + AGCUCACACCAAUGGACACACAUC 24 11165

BCLllA-10726 + GACGGCUCGGUUCACAUC 18 11166

BCLllA-10727 + CGACGGCUCGGUUCACAUC 19 11167

BCLllA-9568 + ACGACGGCUCGGUUCACAUC 20 11168

BCLllA-10728 + GACGACGGCUCGGUUCACAUC 21 11169

BCLllA-10729 + GGACGACGGCUCGGUUCACAUC 22 11170

BCLllA-10730 + CGGACGACGGCUCGGUUCACAUC 23 11171

BCLllA-10731 + GCGGACGACGGCUCGGU UCACAUC 24 11172

BCLllA-10732 + U UAGAAAGAAGGAGACUC 18 11173

BCLllA-10733 + G U U AG AAAG AAGG AG ACU C 19 11174

BCLllA-10734 + GGUUAGAAAGAAGGAGACUC 20 11175

BCLllA-10735 + GGGUUAGAAAGAAGGAGACUC 21 11176

BCLllA-10736 + CGGGUUAGAAAGAAGGAGACUC 22 11177

BCLllA-10737 + CCGGGUUAGAAAGAAGGAGACUC 23 11178

BCLllA-10738 + GCCGGGU UAGAAAGAAGGAGACUC 24 11179

BCLllA-10739 + UCUCUUUUACCUCGACUC 18 11180

BCLllA-10740 + AUCUCUUU UACCUCGACUC 19 11181

BCLllA-10741 + UAUCUCUU UUACCUCGACUC 20 11182

BCLllA-10742 + UUAUCUCU UUUACCUCGACUC 21 11183

BCLllA-10743 + UUUAUCUCUUUUACCUCGACUC 22 11184

BCLllA-10744 + CUUUAUCUCUUUUACCUCGACUC 23 11185

BCLllA-10745 + CCUU UAUCUCUUU UACCUCGACUC 24 11186

BCLllA-10746 + CUCUCGGAGGUUUUUCUC 18 11187 BCLllA-10747 + ACUCUCGGAGGUUUUUCUC 19 11188

BCLllA-10748 + GACUCUCGGAGGUUUUUCUC 20 11189

BCLllA-10749 + CGACUCUCGGAGGUUU UUCUC 21 11190

BCLllA-10750 + UCGACUCUCGGAGGUU UUUCUC 22 11191

BCLllA-10751 + CUCGACUCUCGGAGGU UUUUCUC 23 11192

BCLllA-10752 + CCUCGACUCUCGGAGGUUUUUCUC 24 11193

BCLllA-10753 + AAAAAAAAAAAAAAAAAG 18 11194

BCLllA-10754 + AAAAAAAAAAAAAAAAAAG 19 11195

BCLllA-4526 + AAAAAAAAAAAAAAAAAAAG 20 11196

BCLllA-10755 + AAAAAAAAAAAAAAAAAAAAG 21 11197

BCLllA-10756 + AAAAAAAAAAAAAAAAAAAAAG 22 11198

BCLllA-10757 + AAAAAAAAAAAAAAAAAAAAAAG 23 11199

BCLllA-10758 + AAAAAAAAAAAAAAAAAAAAAAAG 24 11200

BCLllA-10759 + GAGAGCCGGGUUAGAAAG 18 11201

BCLllA-10760 + GGAGAGCCGGGUUAGAAAG 19 11202

BCLllA-10761 + GGGAGAGCCGGGUUAGAAAG 20 11203

BCLllA-10762 + CGGGAGAGCCGGGUUAGAAAG 21 11204

BCLllA-10763 + UCGGGAGAGCCGGGUUAGAAAG 22 11205

BCLllA-10764 + AUCGGGAGAGCCGGGUUAGAAAG 23 11206

BCLllA-10765 + CAUCGGGAGAGCCGGGU UAGAAAG 24 11207

BCLllA-10766 + GGGCGAGCAGGAGAGAAG 18 11208

BCLllA-10767 + AGGGCGAGCAGGAGAGAAG 19 11209

BCLllA-4629 + CAGGGCGAGCAGGAGAGAAG 20 11210

BCLllA-10768 + GCAGGGCGAGCAGGAGAGAAG 21 11211

BCLllA-10769 + GGCAGGGCGAGCAGGAGAGAAG 22 11212

BCLllA-10770 + GGGCAGGGCGAGCAGGAGAGAAG 23 11213

BCLllA-10771 + UGGGCAGGGCGAGCAGGAGAGAAG 24 11214

BCLllA-10772 + AGAAGGGGAGGAGGGAAG 18 11215

BCLllA-10773 + GAGAAGGGGAGGAGGGAAG 19 11216

BCLllA-4577 + AGAGAAGGGGAGGAGGGAAG 20 11217

BCLllA-10774 + GAGAGAAGGGGAGGAGGGAAG 21 11218

BCLllA-10775 + GGAGAGAAGGGGAGGAGGGAAG 22 11219

BCLllA-10776 + AGGAGAGAAGGGGAGGAGGGAAG 23 11220

BCLllA-10777 + CAGGAGAGAAGGGGAGGAGGGAAG 24 11221

BCLllA-10778 + ACACGGCAAUGGUUCCAG 18 11222

BCLllA-10779 + UACACGGCAAUGGUUCCAG 19 11223

BCLllA-10780 + AUACACGGCAAUGGUUCCAG 20 11224

BCLllA-10781 + CAUACACGGCAAUGGU UCCAG 21 11225

BCLllA-10782 + GCAUACACGGCAAUGGU UCCAG 22 11226

BCLllA-10783 + UGCAUACACGGCAAUGGUUCCAG 23 11227

BCLllA-10784 + GUGCAUACACGGCAAUGGUUCCAG 24 11228

BCLllA-10785 + CAUGGGCAGGGCGAGCAG 18 11229 BCLllA-10786 + ACAUGGGCAGGGCGAGCAG 19 11230

BCLllA-10787 + AACAUGGGCAGGGCGAGCAG 20 11231

BCLllA-10788 + AAACAUGGGCAGGGCGAGCAG 21 11232

BCLllA-10789 + AAAACAUGGGCAGGGCGAGCAG 22 11233

BCLllA-10790 + CAAAACAUGGGCAGGGCGAGCAG 23 11234

BCLllA-10791 + ACAAAACAUGGGCAGGGCGAGCAG 24 11235

BCLllA-10792 + GGAGAGAGAGAGAGAGAG 18 11236

BCLllA-10793 + GGGAGAGAGAGAGAGAGAG 19 11237

BCLllA-4999 + AGGGAGAGAGAGAGAGAGAG 20 11238

BCLllA-10794 + GAGGGAGAGAGAGAGAGAGAG 21 11239

BCLllA-10795 + AGAGGGAGAGAGAGAGAGAGAG 22 11240

BCLllA-10796 + UAGAGGGAGAGAGAGAGAGAGAG 23 11241

BCLllA-10797 + AUAGAGGGAGAGAGAGAGAGAGAG 24 11242

BCLllA-10798 + AAAGAGGGAGAGAGAGAG 18 11243

BCLllA-10799 + AAAAGAGGGAGAGAGAGAG 19 11244

BCLllA-4916 + AAAAAGAGGGAGAGAGAGAG 20 11245

BCLllA-10800 + AAAAAAGAGGGAGAGAGAGAG 21 11246

BCLllA-10801 + AAAAAAAGAGGGAGAGAGAGAG 22 11247

BCLllA-10802 + AAAAAAAAGAGGGAGAGAGAGAG 23 11248

BCLllA-10803 + AAAAAAAAAGAGGGAGAGAGAGAG 24 11249

BCLllA-10804 + GCAGGGCGAGCAGGAGAG 18 11250

BCLllA-10805 + GGCAGGGCGAGCAGGAGAG 19 11251

BCLllA-4870 + GGGCAGGGCGAGCAGGAGAG 20 11252

BCLllA-10806 + UGGGCAGGGCGAGCAGGAGAG 21 11253

BCLllA-10807 + AUGGGCAGGGCGAGCAGGAGAG 22 11254

BCLllA-10808 + CAUGGGCAGGGCGAGCAGGAGAG 23 11255

BCLllA-10809 + ACAUGGGCAGGGCGAGCAGGAGAG 24 11256

BCLllA-10810 + GUGGCGUGGCCGGGAGAG 18 11257

BCLllA-10811 + GGUGGCGUGGCCGGGAGAG 19 11258

BCLllA-10812 + CGGUGGCGUGGCCGGGAGAG 20 11259

BCLllA-10813 + GCGGUGGCGUGGCCGGGAGAG 21 11260

BCLllA-10814 + GGCGGUGGCGUGGCCGGGAGAG 22 11261

BCLllA-10815 + CGGCGGUGGCGUGGCCGGGAGAG 23 11262

BCLllA-10816 + GCGGCGGUGGCGUGGCCGGGAGAG 24 11263

BCLllA-10817 + GGGGAGGGGCGGGCCGAG 18 11264

BCLllA-10818 + GGGGGAGGGGCGGGCCGAG 19 11265

BCLllA-4677 + CGGGGGAGGGGCGGGCCGAG 20 11266

BCLllA-10819 + CCGGGGGAGGGGCGGGCCGAG 21 11267

BCLllA-10820 + CCCGGGGGAGGGGCGGGCCGAG 22 11268

BCLllA-10821 + CCCCGGGGGAGGGGCGGGCCGAG 23 11269

BCLllA-10822 + CCCCCGGGGGAGGGGCGGGCCGAG 24 11270

BCLllA-10823 + AAACAUGGGCAGGGCGAG 18 11271 BCLllA-10824 + A A A AC A UGGGCAGGGCGAG 19 11272

BCLllA-10825 + CAAAACAUGGGCAGGGCGAG 20 11273

BCLllA-10826 + ACAAAACAUGGGCAGGGCGAG 21 11274

BCLllA-10827 + C ACA AAACAU G GG CAG G G CG AG 22 11275

BCLllA-10828 + ACACAAAACAUGGGCAGGGCGAG 23 11276

BCLllA-10829 + CACA CAAAACAUGGGCAGGGCGAG 24 11277

BCLllA-10830 + AGCAGGAGAGAAGGGGAG 18 11278

BCLllA-10831 + GAGCAGGAGAGAAGGGGAG 19 11279

BCLllA-5082 + CGAGCAGGAGAGAAGGGGAG 20 11280

BCLllA-10832 + GCGAGCAGGAGAGAAGGGGAG 21 11281

BCLllA-10833 + GGCGAGCAGGAGAGAAGGGGAG 22 11282

BCLllA-10834 + GGGCGAGCAGGAGAGAAGGGGAG 23 11283

BCLllA-10835 + AGGGCGAGCAGGAGAGAAGGGGAG 24 11284

BCLllA-10836 + AAUGGCCAGUGCGGGGAG 18 11285

BCLllA-10837 + CAAUGGCCAGUGCGGGGAG 19 11286

BCLllA-9572 + CCAAUGGCCAGUGCGGGGAG 20 11287

BCLllA-10838 + GCCAAUGGCCAGUGCGGGGAG 21 11288

BCLllA-10839 + AGCCAAUGGCCAGUGCGGGGAG 22 11289

BCLllA-10840 + AAGCCAAUGGCCAGUGCGGGGAG 23 11290

BCLllA-10841 + CAAGCCAAUGGCCAGUGCGGGGAG 24 11291

BCLllA-10842 + GAGAGAGAAGAGAGAUAG 18 11292

BCLllA-10843 + AGAGAGAGAAGAGAGAUAG 19 11293

BCLllA-9740 + GAGAGAGAGAAGAGAGAUAG 20 11294

BCLllA-10844 + AGAGAGAGAGAAGAGAGAUAG 21 11295

BCLllA-10845 + GAGAGAGAGAGAAGAGAGAUAG 22 11296

BCLllA-10846 + GGAGAGAGAGAGAAGAGAGAUAG 23 11297

BCLllA-10847 + GGGAGAGAGAGAGAAGAGAGAUAG 24 11298

BCLllA-10848 + CGCCAGACGCGGCCCCCG 18 11299

BCLllA-10849 + ACGCCAGACGCGGCCCCCG 19 11300

BCLllA-4351 + GACGCCAGACGCGGCCCCCG 20 11301

BCLllA-10850 + GGACGCCAGACGCGGCCCCCG 21 11302

BCLllA-10851 + CGGACGCCAGACGCGGCCCCCG 22 11303

BCLllA-10852 + GCGGACGCCAGACGCGGCCCCCG 23 11304

BCLllA-10853 + CGCGGACGCCAGACGCGGCCCCCG 24 11305

BCLllA-10854 + CGGGGGAGGGGCGGGCCG 18 11306

BCLllA-10855 + CCGGGGGAGGGGCGGGCCG 19 11307

BCLllA-4642 + CCCGGGGGAGGGGCGGGCCG 20 11308

BCLllA-10856 + CCCCGGGGGAGGGGCGGGCCG 21 11309

BCLllA-10857 + CCCCCGGGGGAGGGGCGGGCCG 22 11310

BCLllA-10858 + GCCCCCGGGGGAGGGGCGGGCCG 23 11311

BCLllA-10859 + GGCCCCCGGGGGAGGGGCGGGCCG 24 11312

BCLllA-10860 + GCGGCGGCGGCGGCGGCG 18 11313 BCLllA-10861 + GGCGGCGGCGGCGGCGGCG 19 11314

BCLllA-5097 + CGGCGGCGGCGGCGGCGGCG 20 11315

BCLllA-10862 + GCGGCGGCGGCGGCGGCGGCG 21 11316

BCLllA-10863 + GGCGGCGGCGGCGGCGGCGGCG 22 11317

BCLllA-10864 + CGGCGGCGGCGGCGGCGGCGGCG 23 11318

BCLllA-10865 + GCGGCGGCGGCGGCGGCGGCGGCG 24 11319

BCLllA-10866 + AGGGGGAGGUGCGGGGCG 18 11320

BCLllA-10867 + GAGGGGGAGGUGCGGGGCG 19 11321

BCLllA-9749 + GGAGGGGGAGGUGCGGGGCG 20 11322

BCLllA-10868 + GGGAGGGGGAGGUGCGGGGCG 21 11323

BCLllA-10869 + GGGGAGGGGGAGGUGCGGGGCG 22 11324

BCLllA-10870 + CGGGGAGGGGGAGGUGCGGGGCG 23 11325

BCLllA-10871 + GCGGGGAGGGGGAGGUGCGGGGCG 24 11326

BCLllA-10872 + GGCCGAGGGGAGGGGGCG 18 11327

BCLllA-10873 + GGGCCGAGGGGAGGGGGCG 19 11328

BCLllA-5099 + CGGGCCGAGGGGAGGGGGCG 20 11329

BCLllA-10874 + GCGGGCCGAGGGGAGGGGGCG 21 11330

BCLllA-10875 + GGCGGGCCGAGGGGAGGGGGCG 22 11331

BCLllA-10876 + GGGCGGGCCGAGGGGAGGGGGCG 23 11332

BCLllA-10877 + GGGGCGGGCCGAGGGGAGGGGGCG 24 11333

BCLllA-10878 + AAUAAUACAAAGAUGGCG 18 11334

BCLllA-10879 + A A A U A A U AC A A AG A U G G CG 19 11335

BCLllA-10880 + GAAAUAAUACAAAGAUGGCG 20 11336

BCLllA-10881 + AG AAA U A A U AC A A AG A U G G CG 21 11337

BCLllA-10882 + UAGAAAUAAUACAAAGAUGGCG 22 11338

BCLllA-10883 + UUAGAAAUAAUACAAAGAUGGCG 23 11339

BCLllA-10884 + AUUAGAAAUAAUACAAAGAUGGCG 24 11340

BCLllA-10885 + AAGCCAAUGGCCAGUGCG 18 11341

BCLllA-10886 + CAAGCCAAUGGCCAGUGCG 19 11342

BCLllA-9751 + ACAAGCCAAUGGCCAGUGCG 20 11343

BCLllA-10887 + GACAAGCCAAUGGCCAGUGCG 21 11344

BCLllA-10888 + GGACAAGCCAAUGGCCAGUGCG 22 11345

BCLllA-10889 + AGGACAAGCCAAUGGCCAGUGCG 23 11346

BCLllA-10890 + CAGGACAAGCCAAUGGCCAGUGCG 24 11347

BCLllA-6490 + GGGUUUGCCUUGCUUGCG 18 11348

BCLllA-6491 + GGGGUUUGCCUUGCUUGCG 19 11349

BCLllA-6492 + UGGGGUUUGCCUUGCUUGCG 20 11350

BCLllA-6493 + CUGGGGUUUGCCUUGCUUGCG 21 11351

BCLllA-6494 + GCUGGGGUUUGCCU UGCUUGCG 22 11352

BCLllA-6495 + UGCUGGGGUU UGCCUUGCUUGCG 23 11353

BCLllA-6496 + GUGCUGGGGUUUGCCU UGCUUGCG 24 11354

BCLllA-10891 + CAGGGGUGGGAGGAAAGG 18 11355 BCLllA-10892 + GCAGGGGUGGGAGGAAAGG 19 11356

BCLllA-10893 + GGCAGGGGUGGGAGGAAAGG 20 11357

BCLllA-10894 + UGGCAGGGGUGGGAGGAAAGG 21 11358

BCLllA-10895 + GUGGCAGGGGUGGGAGGAAAGG 22 11359

BCLllA-10896 + GGUGGCAGGGGUGGGAGGAAAGG 23 11360

BCLllA-10897 + GGGUGGCAGGGGUGGGAGGAAAGG 24 11361

BCLllA-10898 + ACACAAAACAUGGGCAGG 18 11362

BCLllA-10899 + CACACAAAACAUGGGCAGG 19 11363

BCLllA-10900 + ACACACAAAACAUGGGCAGG 20 11364

BCLllA-10901 + GACACACAAAACAUGGGCAGG 21 11365

BCLllA-10902 + AGACACACAAAACAUGGGCAGG 22 11366

BCLllA-10903 + GAGACACACAAAACAUGGGCAGG 23 11367

BCLllA-10904 + AGAGACACACAAAACAUGGGCAGG 24 11368

BCLllA-10905 + A A A A A A A A A A AAA AG AG G 18 11369

BCLllA-10906 + AAAAAAAAAAAAAAAGAGG 19 11370

BCLllA-4903 + A AAAAAAAAAAAAAAAG AG G 20 11371

BCLllA-10907 + A A A A A A A A A A A A A A A A AG AG G 21 11372

BCLllA-10908 + A AAAAAAAAAAAAAAAAAG AG G 22 11373

BCLllA-10909 + A A A A A A A A A A A A A A A AAA AG AG G 23 11374

BCLllA-10910 + A AAAAAAAAAAAAAAAAAAAG AG G 24 11375

BCLllA-10911 + AGAGAAGAGAGAUAGAGG 18 11376

BCLllA-10912 + GAGAGAAGAGAGAUAGAGG 19 11377

BCLllA-10913 + AGAGAGAAGAGAGAUAGAGG 20 11378

BCLllA-10914 + GAGAGAGAAGAGAGAUAGAGG 21 11379

BCLllA-10915 + AGAGAGAGAAGAGAGAUAGAGG 22 11380

BCLllA-10916 + GAGAGAGAGAAGAGAGAUAGAGG 23 11381

BCLllA-10917 + AGAGAGAGAGAAGAGAGAUAGAGG 24 11382

BCLllA-10918 + GCAGGAGAGAAGGGGAGG 18 11383

BCLllA-10919 + AGCAGGAGAGAAGGGGAGG 19 11384

BCLllA-4408 + GAGCAGGAGAGAAGGGGAGG 20 11385

BCLllA-10920 + CGAGCAGGAGAGAAGGGGAGG 21 11386

BCLllA-10921 + GCGAGCAGGAGAGAAGGGGAGG 22 11387

BCLllA-10922 + GGCGAGCAGGAGAGAAGGGGAGG 23 11388

BCLllA-10923 + GGGCGAGCAGGAGAGAAGGGGAGG 24 11389

BCLllA-10924 + AUGGCCAGUGCGGGGAGG 18 11390

BCLllA-10925 + AAUGGCCAGUGCGGGGAGG 19 11391

BCLllA-9756 + CAAUGGCCAGUGCGGGGAGG 20 11392

BCLllA-10926 + CCAAUGGCCAGUGCGGGGAGG 21 11393

BCLllA-10927 + GCCAAUGGCCAGUGCGGGGAGG 22 11394

BCLllA-10928 + AGCCAAUGGCCAGUGCGGGGAGG 23 11395

BCLllA-10929 + AAGCCAAUGGCCAGUGCGGGGAGG 24 11396

BCLllA-10930 + GCCAGACGCGGCCCCCGG 18 11397 BCLllA-10931 + CGCCAGACGCGGCCCCCGG 19 11398

BCLllA-4561 + ACGCCAGACGCGGCCCCCGG 20 11399

BCLllA-10932 + GACGCCAGACGCGGCCCCCGG 21 11400

BCLllA-10933 + GGACGCCAGACGCGGCCCCCGG 22 11401

BCLllA-10934 + CGGACGCCAGACGCGGCCCCCGG 23 11402

BCLllA-10935 + GCGGACGCCAGACGCGGCCCCCGG 24 11403

BCLllA-10936 + CGGCGGUGGCGUGGCCGG 18 11404

BCLllA-10937 + GCGGCGGUGGCGUGGCCGG 19 11405

BCLllA-10938 + CGCGGCGGUGGCGUGGCCGG 20 11406

BCLllA-10939 + CCGCGGCGGUGGCGUGGCCGG 21 11407

BCLllA-10940 + GCCGCGGCGGUGGCGUGGCCGG 22 11408

BCLllA-10941 + CGCCGCGGCGGUGGCGUGGCCGG 23 11409

BCLllA-10942 + GCGCCGCGGCGGUGGCGUGGCCGG 24 11410

BCLllA-10943 + CGGCGGCGGCGGCGGCGG 18 11411

BCLllA-10944 + GCGGCGGCGGCGGCGGCGG 19 11412

BCLllA-4479 + GGCGGCGGCGGCGGCGGCGG 20 11413

BCLllA-10945 + CGGCGGCGGCGGCGGCGGCGG 21 11414

BCLllA-10946 + GCGGCGGCGGCGGCGGCGGCGG 22 11415

BCLllA-10947 + GGCGGCGGCGGCGGCGGCGGCGG 23 11416

BCLllA-10948 + CGGCGGCGGCGGCGGCGGCGGCGG 24 11417

BCLllA-10949 + CGGCUCGGUUCACAUCGG 18 11418

BCLllA-10950 + ACGGCUCGGUUCACAUCGG 19 11419

BCLllA-10951 + GACGGCUCGGUUCACAUCGG 20 11420

BCLllA-10952 + CGACGGCUCGGUUCACAUCGG 21 11421

BCLllA-10953 + ACGACGGCUCGGUUCACAUCGG 22 11422

BCLllA-10954 + GACGACGGCUCGGUUCACAUCGG 23 11423

BCLllA-10955 + GGACGACGGCUCGGUUCACAUCGG 24 11424

BCLllA-10956 + AGGGGUGGGAGGAAAGGG 18 11425

BCLllA-10957 + CAGGGGUGGGAGGAAAGGG 19 11426

BCLllA-9759 + GCAGGGGUGGGAGGAAAGGG 20 11427

BCLllA-10958 + GGCAGGGGUGGGAGGAAAGGG 21 11428

BCLllA-10959 + UGGCAGGGGUGGGAGGAAAGGG 22 11429

BCLllA-10960 + GUGGCAGGGGUGGGAGGAAAGGG 23 11430

BCLllA-10961 + GGUGGCAGGGGUGGGAGGAAAGGG 24 11431

BCLllA-10962 + GCGAGCAGGAGAGAAGGG 18 11432

BCLllA-10963 + GGCGAGCAGGAGAGAAGGG 19 11433

BCLllA-4873 + GGGCGAGCAGGAGAGAAGGG 20 11434

BCLllA-10964 + AGGGCGAGCAGGAGAGAAGGG 21 11435

BCLllA-10965 + CAGGGCGAGCAGGAGAGAAGGG 22 11436

BCLllA-10966 + GCAGGGCGAGCAGGAGAGAAGGG 23 11437

BCLllA-10967 + GGCAGGGCGAGCAGGAGAGAAGGG 24 11438

BCLllA-10968 + AAGAAAGGGGUGGCAGGG 18 11439 BCLllA-10969 + GAAGAAAGGGGUGGCAGGG 19 11440

BCLllA-10970 + AGAAGAAAGGGGUGGCAGGG 20 11441

BCLllA-10971 + GAGAAGAAAGGGGUGGCAGGG 21 11442

BCLllA-10972 + AGAGAAGAAAGGGGUGGCAGGG 22 11443

BCLllA-10973 + GAGAGAAGAAAGGGGUGGCAGGG 23 11444

BCLllA-10974 + GGAGAGAAGAAAGGGGUGGCAGGG 24 11445

BCLllA-10975 + GGAGGGGCGGGCCGAGGG 18 11446

BCLllA-10976 + GGGAGGGGCGGGCCGAGGG 19 11447

BCLllA-4875 + GGGGAGGGGCGGGCCGAGGG 20 11448

BCLllA-10977 + GGGGGAGGGGCGGGCCGAGGG 21 11449

BCLllA-10978 + CGGGGGAGGGGCGGGCCGAGGG 22 11450

BCLllA-10979 + CCGGGGGAGGGGCGGGCCGAGGG 23 11451

BCLllA-10980 + CCCGGGGGAGGGGCGGGCCGAGGG 24 11452

BCLllA-10981 + GAGAGAAGGGGAGGAGGG 18 11453

BCLllA-10982 + GGAGAGAAGGGGAGGAGGG 19 11454

BCLllA-4998 + AGGAGAGAAGGGGAGGAGGG 20 11455

BCLllA-10983 + CAGGAGAGAAGGGGAGGAGGG 21 11456

BCLllA-10984 + GCAGGAGAGAAGGGGAGGAGGG 22 11457

BCLllA-10985 + AGCAGGAGAGAAGGGGAGGAGGG 23 11458

BCLllA-10986 + GAGCAGGAGAGAAGGGGAGGAGGG 24 11459

BCLllA-10987 + GCGGCCCCCGGGGGAGGG 18 11460

BCLllA-10988 + CGCGGCCCCCGGGGGAGGG 19 11461

BCLllA-4959 + ACGCGGCCCCCGGGGGAGGG 20 11462

BCLllA-10989 + GACGCGGCCCCCGGGGGAGGG 21 11463

BCLllA-10990 + AGACGCGGCCCCCGGGGGAGGG 22 11464

BCLllA-10991 + CAGACGCGGCCCCCGGGGGAGGG 23 11465

BCLllA-10992 + CCAGACGCGGCCCCCGGGGGAGGG 24 11466

BCLllA-10993 + CCCCGGGGGAGGGGCGGG 18 11467

BCLllA-10994 + CCCCCGGGGGAGGGGCGGG 19 11468

BCLllA-4817 + GCCCCCGGGGGAGGGGCGGG 20 11469

BCLllA-10995 + GGCCCCCGGGGGAGGGGCGGG 21 11470

BCLllA-10996 + CGGCCCCCGGGGGAGGGGCGGG 22 11471

BCLllA-10997 + GCGGCCCCCGGGGGAGGGGCGGG 23 11472

BCLllA-10998 + CGCGGCCCCCGGGGGAGGGGCGGG 24 11473

BCLllA-6504 + GACAUGGUGGGCUGCGGG 18 11474

BCLllA-6505 + AGACAUGGUGGGCUGCGGG 19 11475

BCLllA-6506 + GAGACAUGGUGGGCUGCGGG 20 11476

BCLllA-6507 + CGAGACAUGGUGGGCUGCGGG 21 11477

BCLllA-6508 + GCGAGACAUGGUGGGCUGCGGG 22 11478

BCLllA-6509 + GGCGAGACAUGGUGGGCUGCGGG 23 11479

BCLllA-6510 + CGGCGAGACAUGGUGGGCUGCGGG 24 11480

BCLllA-10999 + GCCAAUGGCCAGUGCGGG 18 11481 BCLllA-11000 + AGCCAAUGGCCAGUGCGGG 19 11482

BCLllA-11001 + AAGCCAAUGGCCAGUGCGGG 20 11483

BCLllA-11002 + CAAGCCAAUGGCCAGUGCGGG 21 11484

BCLllA-11003 + ACAAGCCAAUGGCCAGUGCGGG 22 11485

BCLllA-11004 + GACAAGCCAAUGGCCAGUGCGGG 23 11486

BCLllA-11005 + GGACAAGCCAAUGGCCAGUGCGGG 24 11487

BCLllA-11006 + GGGAGGGGGAGGUGCGGG 18 11488

BCLllA-11007 + GGGGAGGGGGAGGUGCGGG 19 11489

BCLllA-11008 + CGGGGAGGGGGAGGUGCGGG 20 11490

BCLllA-11009 + GCGGGGAGGGGGAGGUGCGGG 21 11491

BCLllA-11010 + UGCGGGGAGGGGGAGGUGCGGG 22 11492

BCLllA-11011 + GUGCGGGGAGGGGGAGGUGCGGG 23 11493

BCLllA-11012 + AGUGCGGGGAGGGGGAGGUGCGGG 24 11494

BCLllA-11013 + CGAGCAGGAGAGAAGGGG 18 11495

BCLllA-11014 + GCGAGCAGGAGAGAAGGGG 19 11496

BCLllA-4476 + GGCGAGCAGGAGAGAAGGGG 20 11497

BCLllA-11015 + GGGCGAGCAGGAGAGAAGGGG 21 11498

BCLllA-11016 + AGGGCGAGCAGGAGAGAAGGGG 22 11499

BCLllA-11017 + CAGGGCGAGCAGGAGAGAAGGGG 23 11500

BCLllA-11018 + GCAGGGCGAGCAGGAGAGAAGGGG 24 11501

BCLllA-11019 + AGAAAGGGGUGGCAGGGG 18 11502

BCLllA-11020 + AAGAAAGGGGUGGCAGGGG 19 11503

BCLllA-9762 + GAAGAAAGGGGUGGCAGGGG 20 11504

BCLllA-11021 + AGAAGAAAGGGGUGGCAGGGG 21 11505

BCLllA-11022 + GAGAAGAAAGGGGUGGCAGGGG 22 11506

BCLllA-11023 + AGAGAAGAAAGGGGUGGCAGGGG 23 11507

BCLllA-11024 + GAGAGAAGAAAGGGGUGGCAGGGG 24 11508

BCLllA-11025 + AUGGACACACAUCAGGGG 18 11509

BCLllA-11026 + AAUGGACACACAUCAGGGG 19 11510

BCLllA-11027 + CAAUGGACACACAUCAGGGG 20 11511

BCLllA-11028 + CCAAUGGACACACAUCAGGGG 21 11512

BCLllA-11029 + ACCAAUGGACACACAUCAGGGG 22 11513

BCLllA-11030 + CACCAAUGGACACACAUCAGGGG 23 11514

BCLllA-11031 + ACACCAAUGGACACACAUCAGGGG 24 11515

BCLllA-11032 + GAGGGGCGGGCCGAGGGG 18 11516

BCLllA-11033 + GGAGGGGCGGGCCGAGGGG 19 11517

BCLllA-4486 + GGGAGGGGCGGGCCGAGGGG 20 11518

BCLllA-11034 + GGGGAGGGGCGGGCCGAGGGG 21 11519

BCLllA-11035 + GGGGGAGGGGCGGGCCGAGGGG 22 11520

BCLllA-11036 + CGGGGGAGGGGCGGGCCGAGGGG 23 11521

BCLllA-11037 + CCGGGGGAGGGGCGGGCCGAGGGG 24 11522

BCLllA-11038 + CAGACGCGGCCCCCGGGG 18 11523 BCLllA-11039 + CCAGACGCGGCCCCCGGGG 19 11524

BCLllA-4816 + GCCAGACGCGGCCCCCGGGG 20 11525

BCLllA-11040 + CGCCAGACGCGGCCCCCGGGG 21 11526

BCLllA-11041 + ACGCCAGACGCGGCCCCCGGGG 22 11527

BCLllA-11042 + GACGCCAGACGCGGCCCCCGGGG 23 11528

BCLllA-11043 + GGACGCCAGACGCGGCCCCCGGGG 24 11529

BCLllA-11044 + CCAAUGGCCAGUGCGGGG 18 11530

BCLllA-11045 + GCCAAUGGCCAGUGCGGGG 19 11531

BCLllA-9763 + AGCCAAUGGCCAGUGCGGGG 20 11532

BCLllA-11046 + AAGCCAAUGGCCAGUGCGGGG 21 11533

BCLllA-11047 + CAAGCCAAUGGCCAGUGCGGGG 22 11534

BCLllA-11048 + ACAAGCCAAUGGCCAGUGCGGGG 23 11535

BCLllA-11049 + GACAAGCCAAUGGCCAGUGCGGGG 24 11536

BCLllA-11050 + GGAGGGGGAGGUGCGGGG 18 11537

BCLllA-11051 + GGGAGGGGGAGGUGCGGGG 19 11538

BCLllA-9764 + GGGGAGGGGGAGGUGCGGGG 20 11539

BCLllA-11052 + CGGGGAGGGGGAGGUGCGGGG 21 11540

BCLllA-11053 + GCGGGGAGGGGGAGGUGCGGGG 22 11541

BCLllA-11054 + UGCGGGGAGGGGGAGGUGCGGGG 23 11542

BCLllA-11055 + GUGCGGGGAGGGGGAGGUGCGGGG 24 11543

BCLllA-11056 + AGACGCGGCCCCCGGGGG 18 11544

BCLllA-11057 + CAGACGCGGCCCCCGGGGG 19 11545

BCLllA-4635 + CCAGACGCGGCCCCCGGGGG 20 11546

BCLllA-11058 + GCCAGACGCGGCCCCCGGGGG 21 11547

BCLllA-11059 + CGCCAGACGCGGCCCCCGGGGG 22 11548

BCLllA-11060 + ACGCCAGACGCGGCCCCCGGGGG 23 11549

BCLllA-11061 + GACGCCAGACGCGGCCCCCGGGGG 24 11550

BCLllA-11062 + UGGGAGGAAAGGGUGGGG 18 11551

BCLllA-11063 + GUGGGAGGAAAGGGUGGGG 19 11552

BCLllA-9766 + GGUGGGAGGAAAGGGUGGGG 20 11553

BCLllA-11064 + GGGUGGGAGGAAAGGGUGGGG 21 11554

BCLllA-11065 + GGGGUGGGAGGAAAGGGUGGGG 22 11555

BCLllA-11066 + AGGGGUGGGAGGAAAGGGUGGGG 23 11556

BCLllA-11067 + CAGGGGUGGGAGGAAAGGGUGGGG 24 11557

BCLllA-11068 + AGACACACAAAACAUGGG 18 11558

BCLllA-11069 + GAGACACACAAAACAUGGG 19 11559

BCLllA-11070 + AGAGACACACAAAACAUGGG 20 11560

BCLllA-11071 + CAGAGACACACAAAACAUGGG 21 11561

BCLllA-11072 + ACAGAGACACACAAAACAUGGG 22 11562

BCLllA-11073 + GACAGAGACACACAAAACAUGGG 23 11563

BCLllA-11074 + GGACAGAGACACACAAAACAUGGG 24 11564

BCLllA-11075 + GCAAUGGUUCCAGAUGGG 18 11565 BCLllA-11076 + GGCAAUGGUUCCAGAUGGG 19 11566

BCLllA-11077 + CGGCAAUGGUUCCAGAUGGG 20 11567

BCLllA-11078 + ACGGCAAUGGUUCCAGAUGGG 21 11568

BCLllA-11079 + CACGGCAAUGGUUCCAGAUGGG 22 11569

BCLllA-11080 + ACACGGCAAUGGUUCCAGAUGGG 23 11570

BCLllA-11081 + UACACGGCAAUGGUUCCAGAUGGG 24 11571

BCLllA-11082 + GUGGGAGGAAAGGGUGGG 18 11572

BCLllA-11083 + GGUGGGAGGAAAGGGUGGG 19 11573

BCLllA-9767 + GGGUGGGAGGAAAGGGUGGG 20 11574

BCLllA-11084 + GGGGUGGGAGGAAAGGGUGGG 21 11575

BCLllA-11085 + AGGGGUGGGAGGAAAGGGUGGG 22 11576

BCLllA-11086 + CAGGGGUGGGAGGAAAGGGUGGG 23 11577

BCLllA-11087 + GCAGGGGUGGGAGGAAAGGGUGGG 24 11578

BCLllA-11088 + AGGGGUGGCAGGGGUGGG 18 11579

BCLllA-11089 + AAGGGGUGGCAGGGGUGGG 19 11580

BCLllA-9768 + AAAGGGGUGGCAGGGGUGGG 20 11581

BCLllA-11090 + GAAAGGGGUGGCAGGGGUGGG 21 11582

BCLllA-11091 + AGAAAGGGGUGGCAGGGGUGGG 22 11583

BCLllA-11092 + AAGAAAGGGGUGGCAGGGGUGGG 23 11584

BCLllA-11093 + GAAGAAAGGGGUGGCAGGGGUGGG 24 11585

BCLllA-11094 + UGAACGUCAGGAGUCUGG 18 11586

BCLllA-11095 + UUGAACGUCAGGAGUCUGG 19 11587

BCLllA-11096 + CU UGAACGUCAGGAGUCUGG 20 11588

BCLllA-11097 + ACUUGAACGUCAGGAGUCUGG 21 11589

BCLllA-11098 + AACUUGAACGUCAGGAGUCUGG 22 11590

BCLllA-11099 + GAACUUGAACGUCAGGAGUCUGG 23 11591

BCLllA-11100 + CGAACUUGAACGUCAGGAGUCUGG 24 11592

BCLllA-11101 + GCCGCGGCGGUGGCGUGG 18 11593

BCLllA-11102 + CGCCGCGGCGGUGGCGUGG 19 11594

BCLllA-11103 + GCGCCGCGGCGGUGGCGUGG 20 11595

BCLllA-11104 + AGCGCCGCGGCGGUGGCGUGG 21 11596

BCLllA-11105 + GAGCGCCGCGGCGGUGGCGUGG 22 11597

BCLllA-11106 + CGAGCGCCGCGGCGGUGGCGUGG 23 11598

BCLllA-11107 + GCGAGCGCCGCGGCGGUGGCGUGG 24 11599

BCLllA-11108 + GGUGGGAGGAAAGGGUGG 18 11600

BCLllA-11109 + GGGUGGGAGGAAAGGGUGG 19 11601

BCLllA-9770 + GGGGUGGGAGGAAAGGGUGG 20 11602

BCLllA-11110 + AGGGGUGGGAGGAAAGGGUGG 21 11603

BCLllA-11111 + CAGGGGUGGGAGGAAAGGGUGG 22 11604

BCLllA-11112 + GCAGGGGUGGGAGGAAAGGGUGG 23 11605

BCLllA-11113 + GGCAGGGGUGGGAGGAAAGGGUGG 24 11606

BCLllA-11114 + GAGAGAAGAAAGGGGUGG 18 11607 BCLllA-11115 + GGAGAGAAGAAAGGGGUGG 19 11608

BCLllA-11116 + GGGAGAGAAGAAAGGGGUGG 20 11609

BCLllA-11117 + CGGGAGAGAAGAAAGGGGUGG 21 11610

BCLllA-11118 + CCGGGAGAGAAGAAAGGGGUGG 22 11611

BCLllA-11119 + GCCGGGAGAGAAGAAAGGGGUGG 23 11612

BCLllA-11120 + GGCCGGGAGAGAAGAAAGGGGUGG 24 11613

BCLllA-11121 + AAGGGGUGGCAGGGGUGG 18 11614

BCLllA-11122 + AAAGGGGUGGCAGGGGUGG 19 11615

BCLllA-11123 + GAAAGGGGUGGCAGGGGUGG 20 11616

BCLllA-11124 + AGAAAGGGGUGGCAGGGGUGG 21 11617

BCLllA-11125 + AAGAAAGGGGUGGCAGGGGUGG 22 11618

BCLllA-11126 + GAAGAAAGGGGUGGCAGGGGUGG 23 11619

BCLllA-11127 + AGAAGAAAGGGGUGGCAGGGGUGG 24 11620

BCLllA-11128 + AGGGAAGAUGAAUUGUGG 18 11621

BCLllA-11129 + CAGGGAAGAUGAAUUGUGG 19 11622

BCLllA-11130 + GCAGGGAAGAUGAAUUGUGG 20 11623

BCLllA-11131 + CGCAGGGAAGAUGAAU UGUGG 21 11624

BCLllA-11132 + GCGCAGGGAAGAUGAAUUGUGG 22 11625

BCLllA-11133 + GGCGCAGGGAAGAUGAAUUGUGG 23 11626

BCLllA-11134 + UGGCGCAGGGAAGAUGAAUUGUGG 24 11627

BCLllA-6524 + UGCUUGCGGCGAGACAUG 18 11628

BCLllA-6525 + U UGCUUGCGGCGAGACAUG 19 11629

BCLllA-6526 + CUUGCUUGCGGCGAGACAUG 20 11630

BCLllA-6527 + CCUUGCU UGCGGCGAGACAUG 21 11631

BCLllA-6528 + GCCUUGCUUGCGGCGAGACAUG 22 11632

BCLllA-6529 + UGCCU UGCUUGCGGCGAGACAUG 23 11633

BCLllA-6530 + UUGCCUUGCUUGCGGCGAGACAUG 24 11634

BCLllA-6544 + GCGAGACAUGGUGGGCUG 18 11635

BCLllA-6545 + GGCGAGACAUGGUGGGCUG 19 11636

BCLllA-5361 + CGGCGAGACAUGGUGGGCUG 20 11637

BCLllA-6546 + GCGGCGAGACAUGGUGGGCUG 21 11638

BCLllA-6547 + UGCGGCGAGACAUGGUGGGCUG 22 11639

BCLllA-6548 + U UGCGGCGAGACAUGGUGGGCUG 23 11640

BCLllA-6549 + CUUGCGGCGAGACAUGGUGGGCUG 24 11641

BCLllA-6550 + U UCCCGUUUGCU UAAGUG 18 11642

BCLllA-6551 + AUUCCCGU UUGCUUAAGUG 19 11643

BCLllA-6552 + AAUUCCCGUUUGCUUAAGUG 20 11644

BCLllA-6553 + GAAUUCCCGU UUGCUUAAGUG 21 11645

BCLllA-6554 + AGAAUUCCCGUUUGCU UAAGUG 22 11646

BCLllA-6555 + GAGAAUUCCCGUUUGCUUAAGUG 23 11647

BCLllA-6556 + CGAGAAUUCCCGUUUGCUUAAGUG 24 11648

BCLllA-11135 + ACAAGCCAAUGGCCAGUG 18 11649 BCLllA-11136 + GACAAGCCAAUGGCCAGUG 19 11650

BCLllA-9773 + GGACAAGCCAAUGGCCAGUG 20 11651

BCLllA-11137 + AGGACAAGCCAAUGGCCAGUG 21 11652

BCLllA-11138 + CAGGACAAGCCAAUGGCCAGUG 22 11653

BCLllA-11139 + CCAGGACAAGCCAAUGGCCAGUG 23 11654

BCLllA-11140 + ACCAGGACAAGCCAAUGGCCAGUG 24 11655

BCLllA-11141 + UGCGGGGAGGGGGAGGUG 18 11656

BCLllA-11142 + GUGCGGGGAGGGGGAGGUG 19 11657

BCLllA-9774 + AGUGCGGGGAGGGGGAGGUG 20 11658

BCLllA-11143 + CAGUGCGGGGAGGGGGAGGUG 21 11659

BCLllA-11144 + CCAGUGCGGGGAGGGGGAGGUG 22 11660

BCLllA-11145 + GCCAGUGCGGGGAGGGGGAGGUG 23 11661

BCLllA-11146 + GGCCAGUGCGGGGAGGGGGAGGUG 24 11662

BCLllA-11147 + GGGUGGGAGGAAAGGGUG 18 11663

BCLllA-11148 + GGGGUGGGAGGAAAGGGUG 19 11664

BCLllA-9775 + AGGGGUGGGAGGAAAGGGUG 20 11665

BCLllA-11149 + CAGGGGUGGGAGGAAAGGGUG 21 11666

BCLllA-11150 + GCAGGGGUGGGAGGAAAGGGUG 22 11667

BCLllA-11151 + GGCAGGGGUGGGAGGAAAGGGUG 23 11668

BCLllA-11152 + UGGCAGGGGUGGGAGGAAAGGGUG 24 11669

BCLllA-11153 + CGCAGGGAAGAUGAAUUG 18 11670

BCLllA-11154 + GCGCAGGGAAGAUGAAUUG 19 11671

BCLllA-9777 + GGCGCAGGGAAGAUGAAUUG 20 11672

BCLllA-11155 + UGGCGCAGGGAAGAUGAAUUG 21 11673

BCLllA-11156 + AUGGCGCAGGGAAGAUGAAUUG 22 11674

BCLllA-11157 + GAUGGCGCAGGGAAGAUGAAUUG 23 11675

BCLllA-11158 + AGAUGGCGCAGGGAAGAUGAAUUG 24 11676

BCLllA-11159 + UUGACAUCCAAAAUAAAU 18 11677

BCLllA-11160 + UUUGACAUCCAAAAUAAAU 19 11678

BCLllA-11161 + U U UUGACAUCCAAAAUAAAU 20 11679

BCLllA-11162 + CUUUUGACAUCCAAAAUAAAU 21 11680

BCLllA-11163 + CCUUUUGACAUCCAAAAUAAAU 22 11681

BCLllA-11164 + GCCUUUUGACAUCCAAAAUAAAU 23 11682

BCLllA-11165 + UGCCUUUUGACAUCCAAAAUAAAU 24 11683

BCLllA-11166 + ACACCAAUGGACACACAU 18 11684

BCLllA-11167 + CACACCAAUGGACACACAU 19 11685

BCLllA-11168 + UCACACCAAUGGACACACAU 20 11686

BCLllA-11169 + CU CACACCAAUGGACACACAU 21 11687

BCLllA-11170 + GCUCACACCAAUGGACACACAU 22 11688

BCLllA-11171 + AGCUCACACCAAUGGACACACAU 23 11689

BCLllA-11172 + AAGCUCACACCAAUGGACACACAU 24 11690

BCLllA-11173 + CGACGGCUCGGUUCACAU 18 11691 BCLllA-11174 + ACGACGGCUCGGUUCACAU 19 11692

BCLllA-9582 + GACGACGGCUCGGUUCACAU 20 11693

BCLllA-11175 + GGACGACGGCUCGGUUCACAU 21 11694

BCLllA-11176 + CGGACGACGGCUCGGUUCACAU 22 11695

BCLllA-11177 + GCGGACGACGGCUCGGUUCACAU 23 11696

BCLllA-11178 + GGCGGACGACGGCUCGGUUCACAU 24 11697

BCLllA-11179 + UGCGGACGUGACGUCCCU 18 11698

BCLllA-11180 + GUGCGGACGUGACGUCCCU 19 11699

BCLllA-11181 + AGUGCGGACGUGACGUCCCU 20 11700

BCLllA-11182 + AAGUGCGGACGUGACGUCCCU 21 11701

BCLllA-11183 + CAAGUGCGGACGUGACGUCCCU 22 11702

BCLllA-11184 + UCAAGUGCGGACGUGACGUCCCU 23 11703

BCLllA-11185 + UUCAAGUGCGGACGUGACGUCCCU 24 11704

BCLllA-6618 + GGCGAGACAUGGUGGGCU 18 11705

BCLllA-6619 + CGGCGAGACAUGGUGGGCU 19 11706

BCLllA-6620 + GCGGCGAGACAUGGUGGGCU 20 11707

BCLllA-6621 + UGCGGCGAGACAUGGUGGGCU 21 11708

BCLllA-6622 + UUGCGGCGAGACAUGGUGGGCU 22 11709

BCLllA-6623 + CUUGCGGCGAGACAUGGUGGGCU 23 11710

BCLllA-6624 + GCUUGCGGCGAGACAUGGUGGGCU 24 11711

BCLllA-11186 + CUCU UUUACCUCGACUCU 18 11712

BCLllA-11187 + UCUCUUUUACCUCGACUCU 19 11713

BCLllA-9585 + AUCUCUUU UACCUCGACUCU 20 11714

BCLllA-11188 + UAUCUCUU UUACCUCGACUCU 21 11715

BCLllA-11189 + UUAUCUCU UUUACCUCGACUCU 22 11716

BCLllA-11190 + UUUAUCUCUUUUACCUCGACUCU 23 11717

BCLllA-11191 + CUUUAUCUCUUUUACCUCGACUCU 24 11718

BCLllA-11192 + U G AG CU G CAAG U U CAAG U 18 11719

BCLllA-11193 + CUGAGCUGCAAGUUCAAGU 19 11720

BCLllA-11194 + CCUGAGCUGCAAGUUCAAGU 20 11721

BCLllA-11195 + CCCUGAGCUGCAAGUUCAAGU 21 11722

BCLllA-11196 + CCCCUGAGCUGCAAGUUCAAGU 22 11723

BCLllA-11197 + CCCCCUGAGCUGCAAGUUCAAGU 23 11724

BCLllA-11198 + CCCCCCUGAGCUGCAAGUUCAAGU 24 11725

BCLllA-11199 + GACAAGCCAAUGGCCAGU 18 11726

BCLllA-11200 + GGACAAGCCAAUGGCCAGU 19 11727

BCLllA-11201 + AGGACAAGCCAAUGGCCAGU 20 11728

BCLllA-11202 + CAGGACAAGCCAAUGGCCAGU 21 11729

BCLllA-11203 + CCAGGACAAGCCAAUGGCCAGU 22 11730

BCLllA-11204 + ACCAGGACAAGCCAAUGGCCAGU 23 11731

BCLllA-11205 + GACCAGGACAAGCCAAUGGCCAGU 24 11732

BCLllA-11206 + CCCUGCGAACUUGAACGU 18 11733 BCLllA-11207 + UCCCUGCGAACUUGAACGU 19 11734

BCLllA-11208 + GUCCCUGCGAACUUGAACGU 20 11735

BCLllA-11209 + CGUCCCUGCGAACUUGAACGU 21 11736

BCLllA-11210 + ACGUCCCUGCGAACUUGAACGU 22 11737

BCLllA-11211 + GACGUCCCUGCGAACU UGAACGU 23 11738

BCLllA-11212 + UGACGUCCCUGCGAACU UGAACGU 24 11739

BCLllA-11213 + GUGCGGGGAGGGGGAGGU 18 11740

BCLllA-11214 + AGUGCGGGGAGGGGGAGGU 19 11741

BCLllA-11215 + CAGUGCGGGGAGGGGGAGGU 20 11742

BCLllA-11216 + CCAGUGCGGGGAGGGGGAGGU 21 11743

BCLllA-11217 + GCCAGUGCGGGGAGGGGGAGGU 22 11744

BCLllA-11218 + GGCCAGUGCGGGGAGGGGGAGGU 23 11745

BCLllA-11219 + UGGCCAGUGCGGGGAGGGGGAGGU 24 11746

BCLllA-11220 + GGGGUGGGAGGAAAGGGU 18 11747

BCLllA-11221 + AGGGGUGGGAGGAAAGGGU 19 11748

BCLllA-9784 + CAGGGGUGGGAGGAAAGGGU 20 11749

BCLllA-11222 + GCAGGGGUGGGAGGAAAGGGU 21 11750

BCLllA-11223 + GGCAGGGGUGGGAGGAAAGGGU 22 11751

BCLllA-11224 + UGGCAGGGGUGGGAGGAAAGGGU 23 11752

BCLllA-11225 + GUGGCAGGGGUGGGAGGAAAGGGU 24 11753

BCLllA-11226 + ACAUCGGGAGAGCCGGGU 18 11754

BCLllA-11227 + CACAUCGGGAGAGCCGGGU 19 11755

BCLllA-11228 + UCACAUCGGGAGAGCCGGGU 20 11756

BCLllA-11229 + UUCACAUCGGGAGAGCCGGGU 21 11757

BCLllA-11230 + GUUCACAUCGGGAGAGCCGGGU 22 11758

BCLllA-11231 + GGUUCACAUCGGGAGAGCCGGGU 23 11759

BCLllA-11232 + CGGU UCACAUCGGGAGAGCCGGGU 24 11760

BCLllA-11233 + GAAAGGGGUGGCAGGGGU 18 11761

BCLllA-11234 + AGAAAGGGGUGGCAGGGGU 19 11762

BCLllA-9785 + AAGAAAGGGGUGGCAGGGGU 20 11763

BCLllA-11235 + GAAGAAAGGGGUGGCAGGGGU 21 11764

BCLllA-11236 + AGAAGAAAGGGGUGGCAGGGGU 22 11765

BCLllA-11237 + GAGAAGAAAGGGGUGGCAGGGGU 23 11766

BCLllA-11238 + AGAGAAGAAAGGGGUGGCAGGGGU 24 11767

BCLllA-11239 + GCAGGGAAGAUGAAUUGU 18 11768

BCLllA-11240 + CGCAGGGAAGAUGAAU UGU 19 11769

BCLllA-9786 + GCGCAGGGAAGAUGAAUUGU 20 11770

BCLllA-11241 + GGCGCAGGGAAGAUGAAUUGU 21 11771

BCLllA-11242 + UGGCGCAGGGAAGAUGAAUUGU 22 11772

BCLllA-11243 + AUGGCGCAGGGAAGAUGAAUUGU 23 11773

BCLllA-11244 + GAUGGCGCAGGGAAGAUGAAUUGU 24 11774

BCLllA-11245 + GCGCAGGGAAGAUGAAUU 18 11775 BCLllA-11246 + GGCGCAGGGAAGAUGAAUU 19 11776

BCLllA-11247 + UGGCGCAGGGAAGAUGAAUU 20 11777

BCLllA-11248 + AUGGCGCAGGGAAGAUGAAUU 21 11778

BCLllA-11249 + GAUGGCGCAGGGAAGAUGAAUU 22 11779

BCLllA-11250 + AGAUGGCGCAGGGAAGAUGAAUU 23 11780

BCLllA-11251 + AAGAUGGCGCAGGGAAGAUGAAUU 24 11781

BCLllA-11252 - GCAGGACUAGAAGCAAAA 18 11782

BCLllA-11253 - CGCAGGACUAGAAGCAAAA 19 11783

BCLllA-11254 - GCGCAGGACUAGAAG C A A A A 20 11784

BCLllA-11255 - CGCGCAGGACUAGAAGCAAAA 21 11785

BCLllA-11256 - G CG CG CAG G ACU AG AAG CAAAA 22 11786

BCLllA-11257 - AGCGCGCAGGACUAGAAG CAAAA 23 11787

BCLllA-11258 - GAGCGCGCAGGACUAGAAGCAAAA 24 11788

BCLllA-6678 - CCCCAGCACUUAAGCAAA 18 11789

BCLllA-6679 - ACCCCAGCACUUAAGCAAA 19 11790

BCLllA-5443 - AACCCCAGCACUUAAGCAAA 20 11791

BCLllA-6680 - AAACCCCAGCACUUAAGCAAA 21 11792

BCLllA-6681 - CAAACCCCAGCACUUAAGCAAA 22 11793

BCLllA-6682 - GCAAACCCCAGCACUUAAGCAAA 23 11794

BCLllA-6683 - GGCAAACCCCAGCACUUAAGCAAA 24 11795

BCLllA-11259 - CG AG G U A A A AG AG A U AAA 18 11796

BCLllA-11260 - U CG AG G U A A A AG AG A U AAA 19 11797

BCLllA-9693 - G U CG AGG U AAAAG AG AU AAA 20 11798

BCLllA-11261 - AGUCGAGGUAAAAGAGAUAAA 21 11799

BCLllA-11262 - GAGUCGAGGUAAAAGAGAUAAA 22 11800

BCLllA-11263 - AG AG U CG AGG U AAAAG AG AU AAA 23 11801

BCLllA-11264 - GAGAGUCGAGGUAAAAGAGAUAAA 24 11802

BCLllA-6698 - ACCCCAGCACUUAAGCAA 18 11803

BCLllA-6699 - AACCCCAGCACUUAAGCAA 19 11804

BCLllA-6700 - AAACCCCAGCACUUAAGCAA 20 11805

BCLllA-6701 - CAAACCCCAGCACUUAAGCAA 21 11806

BCLllA-6702 - GCAAACCCCAGCACUUAAGCAA 22 11807

BCLllA-6703 - GGCAAACCCCAGCACUUAAGCAA 23 11808

BCLllA-6704 - AGGCAAACCCCAGCACUUAAGCAA 24 11809

BCLllA-11265 - CGGCUCUCCCGAUGUGAA 18 11810

BCLllA-11266 - CCGGCUCUCCCGAUGUGAA 19 11811

BCLllA-11267 - CCCGGCUCUCCCGAUGUGAA 20 11812

BCLllA-11268 - ACCCGGCUCUCCCGAUGUGAA 21 11813

BCLllA-11269 - AACCCGGCUCUCCCGAUGUGAA 22 11814

BCLllA-11270 - UAACCCGGCUCUCCCGAUGUGAA 23 11815

BCLllA-11271 - CUAACCCGGCUCUCCCGAUGUGAA 24 11816

BCLllA-11272 - U CG AGG U AAAAG AG AU AA 18 11817 BCLllA-11273 - GUCGAGGUAAAAGAGAUAA 19 11818

BCLllA-9699 - AG U CG AGG U AAAAG AG AU AA 20 11819

BCLllA-11274 - G AG U CG AGG U AAAAG AG AU AA 21 11820

BCLllA-11275 - AGAGUCGAGGUAAAAGAGAUAA 22 11821

BCLllA-11276 - GAG AG U CG AGG U AAAAG AG AU AA 23 11822

BCLllA-11277 - CG AG AG U CG AGG U AAAAG AG AU AA 24 11823

BCLllA-11278 - CUCCGAGAGUCGAGGUAA 18 11824

BCLllA-11279 - CCUCCGAGAGUCGAGGUAA 19 11825

BCLllA-11280 - ACCUCCGAGAGUCGAGGUAA 20 11826

BCLllA-11281 - AACCUCCGAGAGUCGAGGUAA 21 11827

BCLllA-11282 - AAACCUCCGAGAGUCGAGGUAA 22 11828

BCLllA-11283 - AAAACCUCCGAGAGUCGAGGUAA 23 11829

BCLllA-11284 - AAAAACCUCCGAGAGUCGAGGUAA 24 11830

BCLllA-11285 - ACUUGAACUUGCAGCUCA 18 11831

BCLllA-11286 - CACUUGAACUUGCAGCUCA 19 11832

BCLllA-9705 - GCACUUGAACUUGCAGCUCA 20 11833

BCLllA-11287 - CGCACUUGAACUUGCAGCUCA 21 11834

BCLllA-11288 - CCGCACUUGAACUUGCAGCUCA 22 11835

BCLllA-11289 - UCCGCACUUGAACUUGCAGCUCA 23 11836

BCLllA-11290 - GUCCGCACUUGAACUUGCAGCUCA 24 11837

BCLllA-11291 - GCAAAAGCGAGGGGGAGA 18 11838

BCLllA-11292 - AGCAAAAGCGAGGGGGAGA 19 11839

BCLllA-4934 - A AG C A A A AG CGAGGGGGAGA 20 11840

BCLllA-11293 - G A AG C A A A AG CGAGGGGGAGA 21 11841

BCLllA-11294 - AGAAGCAAAAGCGAGGGGGAGA 22 11842

BCLllA-11295 - UAGAAGCAAAAGCGAGGGGGAGA 23 11843

BCLllA-11296 - CUAGAAGCAAAAGCGAGGGGGAGA 24 11844

BCLllA-11297 - GACUAGAAGCAAAAGCGA 18 11845

BCLllA-11298 - GGACUAGAAGCAAAAGCGA 19 11846

BCLllA-9710 - AGGACUAGAAGCAAAAGCGA 20 11847

BCLllA-11299 - CAGGACUAGAAGCAAAAGCGA 21 11848

BCLllA-11300 - GCAGGACUAGAAG C A A A AG CG A 22 11849

BCLllA-11301 - CGCAGGACUAGAAGCAAAAGCGA 23 11850

BCLllA-11302 - GCGCAGGACUAGAAGCAAAAGCGA 24 11851

BCLllA-11303 - AAGCAAAAGCGAGGGGGA 18 11852

BCLllA-11304 - G A AG C A A A AG CGAGGGGGA 19 11853

BCLllA-4972 - AGAAGCAAAAGCGAGGGGGA 20 11854

BCLllA-11305 - UAGAAGCAAAAGCGAGGGGGA 21 11855

BCLllA-11306 - CUAGAAGCAAAAGCGAGGGGGA 22 11856

BCLllA-11307 - ACUAGAAGCAAAAGCGAGGGGGA 23 11857

BCLllA-11308 - GACUAGAAGCAAAAGCGAGGGGGA 24 11858

BCLllA-11309 - G U CG AGG U AAAAG AG AU A 18 11859 BCLllA-11310 - AGUCGAGGUAAAAGAGAUA 19 11860

BCLllA-11311 - GAGUCGAGGUAAAAGAGAUA 20 11861

BCLllA-11312 - AG AG U CG AGG U AAAAG AG AU A 21 11862

BCLllA-11313 - GAGAGUCGAGGUAAAAGAGAUA 22 11863

BCLllA-11314 - CGAGAGUCGAGGUAAAAGAGAUA 23 11864

BCLllA-11315 - CCG AG AG U CG AGG U AAAAG AG AU A 24 11865

BCLllA-11316 - GGGACGUCACGUCCGCAC 18 11866

BCLllA-11317 - AGGGACGUCACGUCCGCAC 19 11867

BCLllA-11318 - CAGGGACGUCACGUCCGCAC 20 11868

BCLllA-11319 - GCAGGGACGUCACGUCCGCAC 21 11869

BCLllA-11320 - CGCAGGGACGUCACGUCCGCAC 22 11870

BCLllA-11321 - U CGCAGGG ACG U CACG U CCG CAC 23 11871

BCLllA-11322 - U U CG CAGGG ACG U CACG U CCG CAC 24 11872

BCLllA-11323 - AUAAUUAUUAAUAAUCAC 18 11873

BCLllA-11324 - AAUAAUUAUUAAUAAUCAC 19 11874

BCLllA-11325 - UAAUAAUUAUUAAUAAUCAC 20 11875

BCLllA-11326 - AUAAUAAUUAUUAAUAAUCAC 21 11876

BCLllA-11327 - AAUAAUAAUUAUUAAUAAUCAC 22 11877

BCLllA-11328 - UAAUAAUAAUUAUUAAUAAUCAC 23 11878

BCLllA-11329 - GUAAUAAUAAUUAUUAAUAAUCAC 24 11879

BCLllA-11330 - CAUUUUUAAAUUUUUCAC 18 11880

BCLllA-11331 - GCAUUUUUAAAUUUUUCAC 19 11881

BCLllA-11332 - UGCAUUUUUAAAUUUUUCAC 20 11882

BCLllA-11333 - AUGCAUUUUUAAAUUUUUCAC 21 11883

BCLllA-11334 - CAUGCAUUUUUAAAUUUUUCAC 22 11884

BCLllA-11335 - GCAUGCAUUUUUAAAUUUUUCAC 23 11885

BCLllA-11336 - UGCAUGCAUUUUUAAAUUUUUCAC 24 11886

BCLllA-11337 - CACGAGAGCGCGCAGGAC 18 11887

BCLllA-11338 - UCACGAGAGCGCGCAGGAC 19 11888

BCLllA-11339 - AUCACGAGAGCGCGCAGGAC 20 11889

BCLllA-11340 - AAUCACGAGAGCGCGCAGGAC 21 11890

BCLllA-11341 - U AAU CACG AG AG CG CG CAGG AC 22 11891

BCLllA-11342 - AUAAUCACGAGAGCGCGCAGGAC 23 11892

BCLllA-11343 - AAUAAUCACGAGAGCGCGCAGGAC 24 11893

BCLllA-11344 - UCGGCCCGCCCCUCCCCC 18 11894

BCLllA-11345 - CUCGGCCCGCCCCUCCCCC 19 11895

BCLllA-9716 - CCUCGGCCCGCCCCUCCCCC 20 11896

BCLllA-11346 - CCCUCGGCCCGCCCCUCCCCC 21 11897

BCLllA-11347 - CCCCUCGGCCCGCCCCUCCCCC 22 11898

BCLllA-11348 - UCCCCUCGGCCCGCCCCUCCCCC 23 11899

BCLllA-11349 - CUCCCCUCGGCCCGCCCCUCCCCC 24 11900

BCLllA-11350 - CUCGGCCCGCCCCUCCCC 18 11901 BCLllA-11351 - CCUCGGCCCGCCCCUCCCC 19 11902

BCLllA-9717 - CCCUCGGCCCGCCCCUCCCC 20 11903

BCLllA-11352 - CCCCUCGGCCCGCCCCUCCCC 21 11904

BCLllA-11353 - UCCCCUCGGCCCGCCCCUCCCC 22 11905

BCLllA-11354 - CUCCCCUCGGCCCGCCCCUCCCC 23 11906

BCLllA-11355 - CCUCCCCUCGGCCCGCCCCUCCCC 24 11907

BCLllA-11356 - CCUCGGCCCGCCCCUCCC 18 11908

BCLllA-11357 - CCCUCGGCCCGCCCCUCCC 19 11909

BCLllA-11358 - CCCCUCGGCCCGCCCCUCCC 20 11910

BCLllA-11359 - UCCCCUCGGCCCGCCCCUCCC 21 11911

BCLllA-11360 - CUCCCCUCGGCCCGCCCCUCCC 22 11912

BCLllA-11361 - CCUCCCCUCGGCCCGCCCCUCCC 23 11913

BCLllA-11362 - CCCUCCCCUCGGCCCGCCCCUCCC 24 11914

BCLllA-11363 - GGGCCGCGUCUGGCGUCC 18 11915

BCLllA-11364 - GGGGCCGCGUCUGGCGUCC 19 11916

BCLllA-11365 - GGGGGCCGCGUCUGGCGUCC 20 11917

BCLllA-11366 - CGGGGGCCGCGUCUGGCGUCC 21 11918

BCLllA-11367 - CCGGGGGCCGCGUCUGGCGUCC 22 11919

BCLllA-11368 - CCCGGGGGCCGCGUCUGGCGUCC 23 11920

BCLllA-11369 - CCCCGGGGGCCGCGUCUGGCGUCC 24 11921

BCLllA-11370 - AG G AC U AG AAG CAAAAG C 18 11922

BCLllA-11371 - C AG G AC U AG AAG CAAAAG C 19 11923

BCLllA-11372 - GCAGGACUAGAAGCAAAAGC 20 11924

BCLllA-11373 - CGCAGGACUAGAAGCAAAAGC 21 11925

BCLllA-11374 - GCGCAGGACUAGAAGCAAAAGC 22 11926

BCLllA-11375 - CGCGCAGGACUAGAAG CAAAAG C 23 11927

BCLllA-11376 - G CG CG CAG G AC U AG AAG CAAAAG C 24 11928

BCLllA-11377 - CCUGACGU UCAAGUUCGC 18 11929

BCLllA-11378 - UCCUGACGUUCAAGUUCGC 19 11930

BCLllA-9566 - CUCCUGACGU UCAAGUUCGC 20 11931

BCLllA-11379 - ACUCCUGACGUUCAAGU UCGC 21 11932

BCLllA-11380 - GACUCCUGACGUUCAAGUUCGC 22 11933

BCLllA-11381 - AGACUCCUGACGUUCAAGUUCGC 23 11934

BCLllA-11382 - CAGACUCCUGACGUUCAAGUUCGC 24 11935

BCLllA-11383 - UAAUAAUUAUUAAUAAUC 18 11936

BCLllA-11384 - AUAAUAAUUAUUAAUAAUC 19 11937

BCLllA-11385 - AAUAAUAAUUAUUAAUAAUC 20 11938

BCLllA-11386 - UAAUAAUAAUUAUUAAUAAUC 21 11939

BCLllA-11387 - GUAAUAAUAAUUAUUAAUAAUC 22 11940

BCLllA-11388 - AGUAAUAAUAAUUAUUAAUAAUC 23 11941

BCLllA-11389 - UAGUAAUAAUAAUUAUUAAUAAUC 24 11942

BCLllA-11390 - AAAAACCCUCAUCCCAUC 18 11943 BCLllA-11391 - AAAAAACCCUCAUCCCAUC 19 11944

BCLllA-9730 - GAAAAAACCCUCAUCCCAUC 20 11945

BCLllA-11392 - GGAAAAAACCCUCAUCCCAUC 21 11946

BCLllA-11393 - GGGAAAAAACCCUCAUCCCAUC 22 11947

BCLllA-11394 - GGGGAAAAAACCCUCAUCCCAUC 23 11948

BCLllA-11395 - GGGGGAAAAAACCCUCAUCCCAUC 24 11949

BCLllA-11396 - CACUUGAACUUGCAGCUC 18 11950

BCLllA-11397 - GCACUUGAACUUGCAGCUC 19 11951

BCLllA-9569 - CGCACUUGAACUUGCAGCUC 20 11952

BCLllA-11398 - CCGCACUUGAACUUGCAGCUC 21 11953

BCLllA-11399 - UCCGCACUUGAACUUGCAGCUC 22 11954

BCLllA-11400 - GUCCGCACUUGAACUUGCAGCUC 23 11955

BCLllA-11401 - CGUCCGCACUUGAACUUGCAGCUC 24 11956

BCLllA-11402 - UGCAUUUUUAAAUUUUUC 18 11957

BCLllA-11403 - AUGCAUUUUUAAAUUUUUC 19 11958

BCLllA-11404 - CAUGCAUUUUUAAAUUUUUC 20 11959

BCLllA-11405 - GCAUGCAUUUUUAAAUUUUUC 21 11960

BCLllA-11406 - UGCAUGCAUUUUUAAAUUUUUC 22 11961

BCLllA-11407 - GUGCAUGCAUUUUUAAAUUUUUC 23 11962

BCLllA-11408 - UGUGCAUGCAUUUUUAAAUUUUUC 24 11963

BCLllA-11409 - G AG G U AAAAG AG A U AAAG 18 11964

BCLllA-11410 - CG AG G U AAAAG AG A U AAAG 19 11965

BCLllA-9571 - U CG AG G U AAAAG AG A U AAAG 20 11966

BCLllA-11411 - GUCGAGGU AAAAG AG A U AAAG 21 11967

BCLllA-11412 - AG U CG AGG U AAAAG AG AU AAAG 22 11968

BCLllA-11413 - GAGUCGAGGUAAAAGAGAUAAAG 23 11969

BCLllA-11414 - AG AG U CG AGG U AAAAG AG AU AAAG 24 11970

BCLllA-11415 - CUUGAACUUGCAGCUCAG 18 11971

BCLllA-11416 - ACUUGAACUUGCAGCUCAG 19 11972

BCLllA-9738 - CACUUGAACUUGCAGCUCAG 20 11973

BCLllA-11417 - GCACUUGAACUUGCAGCUCAG 21 11974

BCLllA-11418 - CGCACUUGAACUUGCAGCUCAG 22 11975

BCLllA-11419 - CCGCACUUGAACUUGCAGCUCAG 23 11976

BCLllA-11420 - UCCGCACUUGAACUUGCAGCUCAG 24 11977

BCLllA-11421 - GAGAAAAACCUCCGAGAG 18 11978

BCLllA-11422 - CGAGAAAAACCUCCGAGAG 19 11979

BCLllA-11423 - ACGAGAAAAACCUCCGAGAG 20 11980

BCLllA-11424 - CACGAGAAAAACCUCCGAGAG 21 11981

BCLllA-11425 - UCACGAGAAAAACCUCCGAGAG 22 11982

BCLllA-11426 - UUCACGAGAAAAACCUCCGAGAG 23 11983

BCLllA-11427 - UUUCACGAGAAAAACCUCCGAGAG 24 11984

BCLllA-11428 - ACU AG AAG CAAAAG CG AG 18 11985 BCLllA-11429 - GACUAGAAGCAAAAGCGAG 19 11986

BCLllA-9739 - GGACUAGAAGCAAAAGCGAG 20 11987

BCLllA-11430 - AGGACUAGAAGCAAAAGCGAG 21 11988

BCLllA-11431 - CAGGACUAGAAGCAAAAGCGAG 22 11989

BCLllA-11432 - GCAGGACUAGAAGCAAAAGCGAG 23 11990

BCLllA-11433 - CGCAGGACUAGAAGCAAAAGCGAG 24 11991

BCLllA-11434 - CGCGUGUGUGGGGGGGAG 18 11992

BCLllA-11435 - CCGCGUGUGUGGGGGGGAG 19 11993

BCLllA-11436 - UCCGCGUGUGUGGGGGGGAG 20 11994

BCLllA-11437 - GUCCGCGUGUGUGGGGGGGAG 21 11995

BCLllA-11438 - AGUCCGCGUGUGUGGGGGGGAG 22 11996

BCLllA-11439 - GAGUCCGCGUGUGUGGGGGGGAG 23 11997

BCLllA-11440 - AGAGUCCGCGUGUGUGGGGGGGAG 24 11998

BCLllA-11441 - GGCCGCGUCUGGCGUCCG 18 11999

BCLllA-11442 - GGGCCGCGUCUGGCGUCCG 19 12000

BCLllA-9574 - GGGGCCGCGUCUGGCGUCCG 20 12001

BCLllA-11443 - GGGGGCCGCGUCUGGCGUCCG 21 12002

BCLllA-11444 - CGGGGGCCGCGUCUGGCGUCCG 22 12003

BCLllA-11445 - CCGGGGGCCGCGUCUGGCGUCCG 23 12004

BCLllA-11446 - CCCGGGGGCCGCGUCUGGCGUCCG 24 12005

BCLllA-11447 - GGACUAGAAGCAAAAGCG 18 12006

BCLllA-11448 - AG G AC U AG AAG CAAAAG CG 19 12007

BCLllA-9748 - CAGGACUAGAAGCAAAAGCG 20 12008

BCLllA-11449 - G C AG G AC U AG AAG CAAAAG CG 21 12009

BCLllA-11450 - CGCAGGACUAGAAGCAAAAGCG 22 12010

BCLllA-11451 - GCGCAGGACUAGAAGCAAAAGCG 23 12011

BCLllA-11452 - CGCGCAGGACUAGAAGCAAAAGCG 24 12012

BCLllA-11453 - AAUAAUCACGAGAGCGCG 18 12013

BCLllA-11454 - UAAUAAUCACGAGAGCGCG 19 12014

BCLllA-11455 - UUAAUAAUCACGAGAGCGCG 20 12015

BCLllA-11456 - AUUAAUAAUCACGAGAGCGCG 21 12016

BCLllA-11457 - UAUUAAUAAUCACGAGAGCGCG 22 12017

BCLllA-11458 - UUAUUAAUAAUCACGAGAGCGCG 23 12018

BCLllA-11459 - AUUAUUAAUAAUCACGAGAGCGCG 24 12019

BCLllA-11460 - UCCUGACGUUCAAGUUCG 18 12020

BCLllA-11461 - CUCCUGACGUUCAAGUUCG 19 12021

BCLllA-11462 - ACUCCUGACGUUCAAGUUCG 20 12022

BCLllA-11463 - GACUCCUGACGUUCAAGUUCG 21 12023

BCLllA-11464 - AGACUCCUGACGUUCAAGUUCG 22 12024

BCLllA-11465 - CAGACUCCUGACGUUCAAGUUCG 23 12025

BCLllA-11466 - CCAGACUCCUGACGUUCAAGUUCG 24 12026

BCLllA-11467 - AGG U AAAAG AG AU AAAGG 18 12027 BCLllA-11468 - G AGG U AAAAG AG AU AAAGG 19 12028

BCLllA-9753 - CGAGGUAAAAGAGAU AAAGG 20 12029

BCLllA-11469 - U CG AGG U AAAAG AG AU AAAGG 21 12030

BCLllA-11470 - GUCGAGGUAAAAGAGAUAAAGG 22 12031

BCLllA-11471 - AG U CG AGG U AAAAG AG AU AAAGG 23 12032

BCLllA-11472 - G AG U CG AGG U AAAAG AG AU AAAGG 24 12033

BCLllA-11473 - CUAGAAGCAAAAGCGAGG 18 12034

BCLllA-11474 - ACUAGAAGCAAAAGCGAGG 19 12035

BCLllA-9755 - GACUAGAAGCAAAAGCGAGG 20 12036

BCLllA-11475 - GGACUAGAAGCAAAAGCGAGG 21 12037

BCLllA-11476 - AGGACUAGAAGCAAAAGCGAGG 22 12038

BCLllA-11477 - CAGGACUAGAAGCAAAAGCGAGG 23 12039

BCLllA-11478 - GCAGGACUAGAAGCAAAAGCGAGG 24 12040

BCLllA-11479 - AGAAGCAAAAGCGAGGGG 18 12041

BCLllA-11480 - U AG A AG C A A A AG CG AG G G G 19 12042

BCLllA-11481 - CUAGAAGCAAAAGCGAGGGG 20 12043

BCLllA-11482 - ACUAGAAGCAAAAGCGAGGGG 21 12044

BCLllA-11483 - GACUAGAAG C A A A AG CG AG G G G 22 12045

BCLllA-11484 - GGACUAGAAGCAAAAGCGAGGGG 23 12046

BCLllA-11485 - AGGACUAGAAGCAAAAGCGAGGGG 24 12047

BCLllA-11486 - GAGUCCGCGUGUGUGGGG 18 12048

BCLllA-11487 - AGAGUCCGCGUGUGUGGGG 19 12049

BCLllA-9577 - UAGAGUCCGCGUGUGUGGGG 20 12050

BCLllA-11488 - UUAGAGUCCGCGUGUGUGGGG 21 12051

BCLllA-11489 - UUUAGAGUCCGCGUGUGUGGGG 22 12052

BCLllA-11490 - UUUUAGAGUCCGCGUGUGUGGGG 23 12053

BCLllA-11491 - AUUUUAGAGUCCGCGUGUGUGGGG 24 12054

BCLllA-11492 - AGAGUCCGCGUGUGUGGG 18 12055

BCLllA-11493 - UAGAGUCCGCGUGUGUGGG 19 12056

BCLllA-9769 - UUAGAGUCCGCGUGUGUGGG 20 12057

BCLllA-11494 - UUUAGAGUCCGCGUGUGUGGG 21 12058

BCLllA-11495 - UUUUAGAGUCCGCGUGUGUGGG 22 12059

BCLllA-11496 - AUUUUAGAGUCCGCGUGUGUGGG 23 12060

BCLllA-11497 - CAUUUUAGAGUCCGCGUGUGUGGG 24 12061

BCLllA-11498 - UAGAGUCCGCGUGUGUGG 18 12062

BCLllA-11499 - UUAGAGUCCGCGUGUGUGG 19 12063

BCLllA-9578 - UUUAGAGUCCGCGUGUGUGG 20 12064

BCLllA-11500 - UUUUAGAGUCCGCGUGUGUGG 21 12065

BCLllA-11501 - AUUUUAGAGUCCGCGUGUGUGG 22 12066

BCLllA-11502 - CAUUUUAGAGUCCGCGUGUGUGG 23 12067

BCLllA-11503 - UCAUUUUAGAGUCCGCGUGUGUGG 24 12068

BCLllA-11504 - CGCUCGCUGCGGCCACUG 18 12069 BCLllA-11505 - GCGCUCGCUGCGGCCACUG 19 12070

BCLllA-11506 - GGCGCUCGCUGCGGCCACUG 20 12071

BCLllA-11507 - CGGCGCUCGCUGCGGCCACUG 21 12072

BCLllA-11508 - GCGGCGCUCGCUGCGGCCACUG 22 12073

BCLllA-11509 - CGCGGCGCUCGCUGCGGCCACUG 23 12074

BCLllA-11510 - CCGCGGCGCUCGCUGCGGCCACUG 24 12075

BCLllA-11511 - GGAUGUCAAAAGGCACUG 18 12076

BCLllA-11512 - UGGAUGUCAAAAGGCACUG 19 12077

BCLllA-11513 - UUGGAUGUCAAAAGGCACUG 20 12078

BCLllA-11514 - UUUGGAUGUCAAAAGGCACUG 21 12079

BCLllA-11515 - UUUUGGAUGUCAAAAGGCACUG 22 12080

BCLllA-11516 - AUUUUGGAUGUCAAAAGGCACUG 23 12081

BCLllA-11517 - UAUUUUGGAUGUCAAAAGGCACUG 24 12082

BCLllA-11518 - UUUUAGAGUCCGCGUGUG 18 12083

BCLllA-11519 - AUUUUAGAGUCCGCGUGUG 19 12084

BCLllA-9581 - CAUUUUAGAGUCCGCGUGUG 20 12085

BCLllA-11520 - UCAUUUUAGAGUCCGCGUGUG 21 12086

BCLllA-11521 - UUCAUUUUAGAGUCCGCGUGUG 22 12087

BCLllA-11522 - UUUCAUUUUAGAGUCCGCGUGUG 23 12088

BCLllA-11523 - CUUUCAUUUUAGAGUCCGCGUGUG 24 12089

BCLllA-11524 - UUAGAGUCCGCGUGUGUG 18 12090

BCLllA-11525 - UUUAGAGUCCGCGUGUGUG 19 12091

BCLllA-9776 - UUUUAGAGUCCGCGUGUGUG 20 12092

BCLllA-11526 - AUUUUAGAGUCCGCGUGUGUG 21 12093

BCLllA-11527 - CAUUUUAGAGUCCGCGUGUGUG 22 12094

BCLllA-11528 - UCAUUUUAGAGUCCGCGUGUGUG 23 12095

BCLllA-11529 - UUCAUUUUAGAGUCCGCGUGUGUG 24 12096

BCLllA-11530 - AAAAAACCCUCAUCCCAU 18 12097

BCLllA-11531 - GAAAAAACCCUCAUCCCAU 19 12098

BCLllA-11532 - GGAAAAAACCCUCAUCCCAU 20 12099

BCLllA-11533 - GGGAAAAAACCCUCAUCCCAU 21 12100

BCLllA-11534 - GGGGAAAAAACCCUCAUCCCAU 22 12101

BCLllA-11535 - GGGGGAAAAAACCCUCAUCCCAU 23 12102

BCLllA-11536 - AGGGGGAAAAAACCCUCAUCCCAU 24 12103

BCLllA-11537 - UAACCCGGCUCUCCCGAU 18 12104

BCLllA-11538 - CUAACCCGGCUCUCCCGAU 19 12105

BCLllA-11539 - UCUAACCCGGCUCUCCCGAU 20 12106

BCLllA-11540 - UUCUAACCCGGCUCUCCCGAU 21 12107

BCLllA-11541 - UUUCUAACCCGGCUCUCCCGAU 22 12108

BCLllA-11542 - CUUUCUAACCCGGCUCUCCCGAU 23 12109

BCLllA-11543 - UCUUUCUAACCCGGCUCUCCCGAU 24 12110

BCLllA-11544 - U U U U CACG AG AAAAACCU 18 12111 BCLllA-11545 - U U U U U CACG AG AAAAACCU 19 12112

BCLllA-11546 - AU U U U U CACG AG AAAAACCU 20 12113

BCLllA-11547 - AAU U U U U CACG AG AAAAACCU 21 12114

BCLllA-11548 - AAAU U U U U CACG AG AAAAACCU 22 12115

BCLllA-11549 - UAAAU U U U U CACG AG AAAAACCU 23 12116

BCLllA-11550 - U UAAAU U U U U CACG AG AAAAACCU 24 12117

BCLllA-11551 - GCACUUGAACUUGCAGCU 18 12118

BCLllA-11552 - CGCACUUGAACUUGCAGCU 19 12119

BCLllA-11553 - CCGCACUUGAACUUGCAGCU 20 12120

BCLllA-11554 - UCCGCACUUGAACUUGCAGCU 21 12121

BCLllA-11555 - GUCCGCACUUGAACUUGCAGCU 22 12122

BCLllA-11556 - CGUCCGCACUUGAACUUGCAGCU 23 12123

BCLllA-11557 - ACGUCCGCACUUGAACUUGCAGCU 24 12124

BCLllA-11558 - CUGAUGAAGAUAUUUUCU 18 12125

BCLllA-11559 - ACUGAUGAAGAUAUUUUCU 19 12126

BCLllA-11560 - CACUGAUGAAGAUAUUUUCU 20 12127

BCLllA-11561 - GCACUGAUGAAGAUAUUUUCU 21 12128

BCLllA-11562 - GGCACUGAUGAAGAUAUUUUCU 22 12129

BCLllA-11563 - AGGCACUGAUGAAGAUAUUUUCU 23 12130

BCLllA-11564 - AAGGCACUGAUGAAGAUAUUUUCU 24 12131

BCLllA-11565 - UGAUGUGUGUCCAUUGGU 18 12132

BCLllA-11566 - CUGAUGUGUGUCCAUUGGU 19 12133

BCLllA-11567 - CCUGAUGUGUGUCCAUUGGU 20 12134

BCLllA-11568 - CCCUGAUGUGUGUCCAUUGGU 21 12135

BCLllA-11569 - CCCCUGAUGUGUGUCCAUUGGU 22 12136

BCLllA-11570 - GCCCCUGAUGUGUGUCCAUUGGU 23 12137

BCLllA-11571 - AGCCCCUGAUGUGUGUCCAUUGGU 24 12138

BCLllA-11572 - AUUUUAGAGUCCGCGUGU 18 12139

BCLllA-11573 - CAUUUUAGAGUCCGCGUGU 19 12140

BCLllA-11574 - UCAUUUUAGAGUCCGCGUGU 20 12141

BCLllA-11575 - UUCAUUUUAGAGUCCGCGUGU 21 12142

BCLllA-11576 - UUUCAUUUUAGAGUCCGCGUGU 22 12143

BCLllA-11577 - CUUUCAUUUUAGAGUCCGCGUGU 23 12144

BCLllA-11578 - UCUUUCAUUUUAGAGUCCGCGUGU 24 12145

BCLllA-11579 - UUUAGAGUCCGCGUGUGU 18 12146

BCLllA-11580 - UUUUAGAGUCCGCGUGUGU 19 12147

BCLllA-9586 - AUUUUAGAGUCCGCGUGUGU 20 12148

BCLllA-11581 - CAUUUUAGAGUCCGCGUGUGU 21 12149

BCLllA-11582 - UCAUUUUAGAGUCCGCGUGUGU 22 12150

BCLllA-11583 - UUCAUUUUAGAGUCCGCGUGUGU 23 12151

BCLllA-11584 - UUUCAUUUUAGAGUCCGCGUGUGU 24 12152

BCLllA-11585 - AUUGCCGUGUAUGCACUU 18 12153 BCLllA-11586 - CAUUGCCGUGUAUGCACUU 19 12154

BCLllA-11587 - CCAUUGCCGUGUAUGCACUU 20 12155

BCLllA-11588 - ACCAUUGCCGUGUAUGCACUU 21 12156

BCLllA-11589 - AACCAUUGCCGUGUAUGCACUU 22 12157

BCLllA-11590 - GAACCAUUGCCGUGUAUGCACUU 23 12158

BCLllA-11591 - GGAACCAUUGCCGUGUAUGCACUU 24 12159

Table 16D provides exemplary targeting domains for knocking down the BCLl 1 A gene selected according to the fourth 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 the 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 BCLl 1 A gene (e.g., reduce or eliminate BCLl 1A gene expression, BCLl 1A protein function, or the level of BCLl 1A protein). One or more gRNA may be used to target an eiCas9 to the promoter region of the BCLl 1 A gene.

Table 16D

BCLllA-11607 + ACUGGCGGGGCGGGGGGGGAG 21 12177

BCLllA-11608 + AACUGGCGGGGCGGGGGGGGAG 22 12178

BCLllA-11609 + AAACUGGCGGGGCGGGGGGGGAG 23 12179

BCLllA-11610 + AAAACUGGCGGGGCGGGGGGGGAG 24 12180

BCLllA-11611 + AGGGAGCGCACGGCAACG 18 12181

BCLllA-11612 + GAGGGAGCGCACGGCAACG 19 12182

BCLllA-10155 + GGAGGGAGCGCACGGCAACG 20 12183

BCLllA-11613 + GGGAGGGAGCGCACGGCAACG 21 12184

BCLllA-11614 + UGGGAGGGAGCGCACGGCAACG 22 12185

BCLllA-11615 + GUGGGAGGGAGCGCACGGCAACG 23 12186

BCLllA-11616 + GGUGGGAGGGAGCGCACGGCAACG 24 12187

BCLllA-11617 + CCCCCCCAUUUUCUUACG 18 12188

BCLllA-11618 + ACCCCCCCAUUU UCUUACG 19 12189

BCLllA-11619 + UACCCCCCCAUU UUCUUACG 20 12190

BCLllA-11620 + CUACCCCCCCAUUUUCU UACG 21 12191

BCLllA-11621 + CCUACCCCCCCAUUUUCUUACG 22 12192

BCLllA-11622 + CCCUACCCCCCCAUU UUCUUACG 23 12193

BCLllA-11623 + UCCCUACCCCCCCAU UU UCUUACG 24 12194

BCLllA-11624 + GGGCGGAGGGAAGCCAGG 18 12195

BCLllA-11625 + CGGGCGGAGGGAAGCCAGG 19 12196

BCLllA-11626 + GCGGGCGGAGGGAAGCCAGG 20 12197

BCLllA-11627 + CGCGGGCGGAGGGAAGCCAGG 21 12198

BCLllA-11628 + GCGCGGGCGGAGGGAAGCCAGG 22 12199

BCLllA-11629 + AGCGCGGGCGGAGGGAAGCCAGG 23 12200

BCLllA-11630 + AAGCGCGGGCGGAGGGAAGCCAGG 24 12201

BCLllA-11631 + CGGAAAGGAGGAAAGAGG 18 12202

BCLllA-11632 + GCGGAAAGGAGGAAAGAGG 19 12203

BCLllA-10187 + GGCGGAAAGGAGGAAAGAGG 20 12204

BCLllA-11633 + CGGCGGAAAGGAGGAAAGAGG 21 12205

BCLllA-11634 + GCGGCGGAAAGGAGGAAAGAGG 22 12206

BCLllA-11635 + AGCGGCGGAAAGGAGGAAAGAGG 23 12207

BCLllA-11636 + AAGCGGCGGAAAGGAGGAAAGAGG 24 12208

BCLllA-11637 + AAACUGGCGGGGCGGGGG 18 12209

BCLllA-11638 + AAAACUGGCGGGGCGGGGG 19 12210

BCLllA-10209 + CAAAACUGGCGGGGCGGGGG 20 12211

BCLllA-11639 + GCAAAACUGGCGGGGCGGGGG 21 12212

BCLllA-11640 + UGCAAAACUGGCGGGGCGGGGG 22 12213

BCLllA-11641 + U UGCAAAACUGGCGGGGCGGGGG 23 12214

BCLllA-11642 + UUUGCAAAACUGGCGGGGCGGGGG 24 12215

BCLllA-11643 + CCACCCCCAGGU UUGCAU 18 12216

BCLllA-11644 + CCCACCCCCAGGUUUGCAU 19 12217

BCLllA-11645 + UCCCACCCCCAGGUUUGCAU 20 12218 BCLllA-11646 + CUCCCACCCCCAGGUUUGCAU 21 12219

BCLllA-11647 + GCUCCCACCCCCAGGUUUGCAU 22 12220

BCLllA-11648 + AGCUCCCACCCCCAGGU UUGCAU 23 12221

BCLllA-11649 + CAGCUCCCACCCCCAGGUUUGCAU 24 12222

BCLllA-11650 + GCCUAAGUUUGGAGGGCU 18 12223

BCLllA-11651 + AGCCUAAGUUUGGAGGGCU 19 12224

BCLllA-11652 + CAGCCUAAGUUUGGAGGGCU 20 12225

BCLllA-11653 + CCAGCCUAAGUUUGGAGGGCU 21 12226

BCLllA-11654 + UCCAGCCUAAGUUUGGAGGGCU 22 12227

BCLllA-11655 + AUCCAGCCUAAGU UUGGAGGGCU 23 12228

BCLllA-11656 + AAUCCAGCCUAAGUUUGGAGGGCU 24 12229

BCLllA-11657 + CCACUUUCUCACUAUUGU 18 12230

BCLllA-11658 + GCCACU UUCUCACUAUUGU 19 12231

BCLllA-10251 + UGCCACUUUCUCACUAU UGU 20 12232

BCLllA-11659 + GUGCCACU UUCUCACUAUUGU 21 12233

BCLllA-11660 + AGUGCCACUU UCUCACUAUUGU 22 12234

BCLllA-11661 + CAGUGCCACUUUCUCACUAUUGU 23 12235

BCLllA-11662 + ACAGUGCCACUUUCUCACUAUUGU 24 12236

BCLllA-11663 - UUAUUUCUCUUUUCGAAA 18 12237

BCLllA-11664 - U UUAUUUCUCUUUUCGAAA 19 12238

BCLllA-10027 - CUUUAUUUCUCUUUUCGAAA 20 12239

BCLllA-11665 - GCUU UAUUUCUCUU UUCGAAA 21 12240

BCLllA-11666 - CGCUUUAUU UCUCUUU UCGAAA 22 12241

BCLllA-11667 - CCGCUUUAUUUCUCUU UUCGAAA 23 12242

BCLllA-11668 - GCCGCUU UAUUUCUCUUUUCGAAA 24 12243

BCLllA-11669 - CGGCGGCGGGGAGGGGAA 18 12244

BCLllA-11670 - GCGGCGGCGGGGAGGGGAA 19 12245

BCLllA-11671 - GGCGGCGGCGGGGAGGGGAA 20 12246

BCLllA-11672 - CGGCGGCGGCGGGGAGGGGAA 21 12247

BCLllA-11673 - GCGGCGGCGGCGGGGAGGGGAA 22 12248

BCLllA-11674 - CGCGGCGGCGGCGGGGAGGGGAA 23 12249

BCLllA-11675 - GCGCGGCGGCGGCGGGGAGGGGAA 24 12250

BCLllA-11676 - UGGGGGGGUAGGGAGGGA 18 12251

BCLllA-11677 - AUGGGGGGGUAGGGAGGGA 19 12252

BCLllA-11678 - AAUGGGGGGGUAGGGAGGGA 20 12253

BCLllA-11679 - AAAUGGGGGGGUAGGGAGGGA 21 12254

BCLllA-11680 - AAAAUGGGGGGGUAGGGAGGGA 22 12255

BCLllA-11681 - GAAAAUGGGGGGGUAGGGAGGGA 23 12256

BCLllA-11682 - AGAAAAUGGGGGGGUAGGGAGGGA 24 12257

BCLllA-11683 - AAAAUGGGGGGGUAGGGA 18 12258

BCLllA-11684 - GAAAAUGGGGGGGUAGGGA 19 12259

BCLllA-10049 - AGAAAAUGGGGGGGUAGGGA 20 12260 BCLllA-11685 - AAGAAAAUGGGGGGGUAGGGA 21 12261

BCLllA-11686 - UAAGAAAAUGGGGGGGUAGGGA 22 12262

BCLllA-11687 - GU AAGAAAAUGGGGGGGUAGGGA 23 12263

BCLllA-11688 - CGUAAGAAAAUGGGGGGGUAGGGA 24 12264

BCLllA-11689 - AAGGGGCCCCCGGCGCUC 18 12265

BCLllA-11690 - AAAGGGGCCCCCGGCGCUC 19 12266

BCLllA-11691 - GAAAGGGGCCCCCGGCGCUC 20 12267

BCLllA-11692 - GGAAAGGGGCCCCCGGCGCUC 21 12268

BCLllA-11693 - UGGAAAGGGGCCCCCGGCGCUC 22 12269

BCLllA-11694 - GUGGAAAGGGGCCCCCGGCGCUC 23 12270

BCLllA-11695 - UGUGGAAAGGGGCCCCCGGCGCUC 24 12271

BCLllA-11696 - CUUUUGUUCCGGCCAGAG 18 12272

BCLllA-11697 - CCUUUUGUUCCGGCCAGAG 19 12273

BCLllA-11698 - GCCUUUUGUUCCGGCCAGAG 20 12274

BCLllA-11699 - CGCCUUUUGUUCCGGCCAGAG 21 12275

BCLllA-11700 - CCGCCUUUUGUUCCGGCCAGAG 22 12276

BCLllA-11701 - GCCGCCUUUUGUUCCGGCCAGAG 23 12277

BCLllA-11702 - UGCCGCCUUUUGUUCCGGCCAGAG 24 12278

BCLllA-11703 - GUGGGUGUGCGUACGGAG 18 12279

BCLllA-11704 - AGUGGGUGUGCGUACGGAG 19 12280

BCLllA-11705 - AAGUGGGUGUGCGUACGGAG 20 12281

BCLllA-11706 - GAAGUGGGUGUGCGUACGGAG 21 12282

BCLllA-11707 - GGAAGUGGGUGUGCGUACGGAG 22 12283

BCLllA-11708 - GGGAAGUGGGUGUGCGUACGGAG 23 12284

BCLllA-11709 - GGGGAAGUGGGUGUGCGUACGGAG 24 12285

BCLllA-11710 - CCGGCGCUCCUGAGUCCG 18 12286

BCLllA-11711 - CCCGGCGCUCCUGAGUCCG 19 12287

BCLllA-10172 - CCCCGGCGCUCCUGAGUCCG 20 12288

BCLllA-11712 - CCCCCGGCGCUCCUGAGUCCG 21 12289

BCLllA-11713 - GCCCCCGGCGCUCCUGAGUCCG 22 12290

BCLllA-11714 - GGCCCCCGGCGCUCCUGAGUCCG 23 12291

BCLllA-11715 - GGGCCCCCGGCGCUCCUGAGUCCG 24 12292

BCLllA-11716 - CAGCCCUCCAAACUUAGG 18 12293

BCLllA-11717 - GCAGCCCUCCAAACUUAGG 19 12294

BCLllA-11718 - CGCAGCCCUCCAAACUUAGG 20 12295

BCLllA-11719 - CCGCAGCCCUCCAAACUUAGG 21 12296

BCLllA-11720 - CCCGCAGCCCUCCAAACUUAGG 22 12297

BCLllA-11721 - ACCCGCAGCCCUCCAAACUUAGG 23 12298

BCLllA-11722 - GACCCGCAGCCCUCCAAACUUAGG 24 12299

BCLllA-11723 - CUCACCGUAAGAAAAUGG 18 12300

BCLllA-11724 - ACUCACCGUAAGAAAAUGG 19 12301

BCLllA-10214 - CACU CACCG U AAG AAAAUGG 20 12302 BCLllA-11725 - CCACUCACCGUAAGAAAAUGG 21 12303

BCLllA-11726 - CCCACUCACCGUAAGAAAAUGG 22 12304

BCLllA-11727 - UCCCACUCACCGUAAGAAAAUGG 23 12305

BCLllA-11728 - U UCCCACUCACCGUAAGAAAAUGG 24 12306

BCLllA-11729 - GAGGCUCAGCUCUCAACU 18 12307

BCLllA-11730 - GGAGGCUCAGCUCUCAACU 19 12308

BCLllA-11731 - UGGAGGCUCAGCUCUCAACU 20 12309

BCLllA-11732 - UUGGAGGCUCAGCUCUCAACU 21 12310

BCLllA-11733 - CUUGGAGGCUCAGCUCUCAACU 22 12311

BCLllA-11734 - ACU UGGAGGCUCAGCUCUCAACU 23 12312

BCLllA-11735 - AACUUGGAGGCUCAGCUCUCAACU 24 12313

BCLllA-11736 - CAACUCACAUGCAAACCU 18 12314

BCLllA-11737 - ACAACUCACAUGCAAACCU 19 12315

BCLllA-10235 - AACAACUCACAUGCAAACCU 20 12316

BCLllA-11738 - GAACAACUCACAUGCAAACCU 21 12317

BCLllA-11739 - CGAACAACUCACAUGCAAACCU 22 12318

BCLllA-11740 - GCGAACAACUCACAUGCAAACCU 23 12319

BCLllA-11741 - UGCGAACAACUCACAUGCAAACCU 24 12320

BCLllA-10351 - UUGAAUAAUCUUUCAUUU 18 12321

BCLllA-10352 - UUUGAAUAAUCUUUCAUUU 19 12322

BCLllA-10353 - U UUUGAAUAAUCUUUCAUUU 20 12323

BCLllA-10354 - U UUUUGAAUAAUCUUUCAUUU 21 12324

BCLllA-10355 - U UUUUUGAAUAAUCUU UCAUUU 22 12325

BCLllA-10356 - CUU UUUUGAAUAAUCU UUCAUUU 23 12326

BCLllA-10357 - UCU UUUUUGAAUAAUCUUUCAUUU 24 12327

BCLllA-11742 - GCUCUAUUUUUUUCUU UU 18 12328

BCLllA-11743 - CGCUCUAU UUUUUUCUUUU 19 12329

BCLllA-11744 - UCGCUCUAUUUUUU UCUUUU 20 12330

BCLllA-11745 - CUCGCUCUAUUUUUUUCUUUU 21 12331

BCLllA-11746 - UCUCGCUCUAUUUUUU UCUUUU 22 12332

BCLllA-11747 - CUCUCGCUCUAUUUUU UUCUUUU 23 12333

BCLllA-11748 - ACUCUCGCUCUAUU UUUUUCUUUU 24 12334

Table 16E provides exemplary targeting domains for knocking down the BCL11A 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, and the 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 BCLl 1 A gene (e.g., reduce or eliminate BCLl 1A gene expression, BCLl 1A protein function, or the level of BCLl 1 A protein). One or more gRNA may be used to target an eiCas9 to the promoter region of the BCLl 1 A gene.

Table 16E

BCLllA-11783 + CCAGGAGCCCGCGCGGCCUGGAAA 24 12369

BCLllA-10371 + ACACACGCGGACUCUAAA 18 12370

BCLllA-10372 + CACACACGCGGACUCUAAA 19 12371

BCLllA-10373 + CCACACACGCGGACUCUAAA 20 12372

BCLllA-10374 + CCCACACACGCGGACUCUAAA 21 12373

BCLllA-10375 + CCCCACACACGCGGACUCUAAA 22 12374

BCLllA-10376 + CCCCCACACACGCGGACUCUAAA 23 12375

BCLllA-10377 + CCCCCCACACACGCGGACUCUAAA 24 12376

BCLllA-11784 + AUUGCAUUCCUUUUCGAA 18 12377

BCLllA-11785 + CAUUGCAUUCCUUUUCGAA 19 12378

BCLllA-11786 + UCAUUGCAUUCCUUUUCGAA 20 12379

BCLllA-11787 + AUCAUUGCAUUCCUUU UCGAA 21 12380

BCLllA-11788 + AAUCAUUGCAUUCCUUUUCGAA 22 12381

BCLllA-11789 + GAAUCAUUGCAUUCCUUUUCGAA 23 12382

BCLllA-11790 + GGAAUCAUUGCAUUCCU UUUCGAA 24 12383

BCLllA-11791 + AGAAAUAAAGCGGCGGAA 18 12384

BCLllA-11792 + GAG AAA U A A AG CG G CG G A A 19 12385

BCLllA-10031 + AGAGAAAUAAAGCGGCGGAA 20 12386

BCLllA-11793 + AAGAGAAAUAAAGCGGCGGAA 21 12387

BCLllA-11794 + A A AG AG A A A U A A AG CG G CG G A A 22 12388

BCLllA-11795 + A A A AG AG A A A U A A AG CG G CG G A A 23 12389

BCLllA-11796 + GAAAAGAGAAAUAAAGCGGCGGAA 24 12390

BCLllA-11797 + CCCGAGGAGAGGACAGCA 18 12391

BCLllA-11798 + GCCCGAGGAGAGGACAGCA 19 12392

BCLllA-11799 + UGCCCGAGGAGAGGACAGCA 20 12393

BCLllA-11800 + UUGCCCGAGGAGAGGACAGCA 21 12394

BCLllA-11801 + UUUGCCCGAGGAGAGGACAGCA 22 12395

BCLllA-11802 + CU UUGCCCGAGGAGAGGACAGCA 23 12396

BCLllA-11803 + ACUUUGCCCGAGGAGAGGACAGCA 24 12397

BCLllA-11804 + CCAAGUUACAGCUCCGCA 18 12398

BCLllA-11805 + UCCAAGUUACAGCUCCGCA 19 12399

BCLllA-11806 + CUCCAAGUUACAGCUCCGCA 20 12400

BCLllA-11807 + CCUCCAAGUUACAGCUCCGCA 21 12401

BCLllA-11808 + GCCUCCAAGUUACAGCUCCGCA 22 12402

BCLllA-11809 + AGCCUCCAAGU UACAGCUCCGCA 23 12403

BCLllA-11810 + GAGCCUCCAAGUUACAGCUCCGCA 24 12404

BCLllA-11811 + GAG CCGG CACAAAAGG CA 18 12405

BCLllA-11812 + GGAGCCGGCA C A A A AG G C A 19 12406

BCLllA-11813 + AG GAG CCGG CAC AAAAG G C A 20 12407

BCLllA-11814 + GAGGAGCCGGCACAAAAGGCA 21 12408

BCLllA-11815 + CG AG G AG CCGG C ACAAAAG G C A 22 12409

BCLllA-11816 + GCGAGGAGCCGGCACAAAAGGCA 23 12410 BCLllA-11817 + CG CG AG G AG CCG G C ACA AAAGG CA 24 12411

BCLllA-11818 + AAAUAGAGCGAGAGUGCA 18 12412

BCLllA-11819 + AAAAUAGAGCGAGAGUGCA 19 12413

BCLllA-11820 + AAAAAUAGAGCGAGAGUGCA 20 12414

BCLllA-11821 + AAAAAAUAGAGCGAGAGUGCA 21 12415

BCLllA-11822 + AAAAAAAU AG AGCGAG AG UGCA 22 12416

BCLllA-11823 + G A A A A A A A UAGAGCGAGAGUGCA 23 12417

BCLllA-11824 + AGAAAAAAAUAGAGCGAGAGUGCA 24 12418

BCLllA-11825 + CCGCGCGGCCUGGAAAGA 18 12419

BCLllA-11826 + CCCGCGCGGCCUGGAAAGA 19 12420

BCLllA-10040 + GCCCGCGCGGCCUGGAAAGA 20 12421

BCLllA-11827 + AGCCCGCGCGGCCUGGAAAGA 21 12422

BCLllA-11828 + GAGCCCGCGCGGCCUGGAAAGA 22 12423

BCLllA-11829 + GGAGCCCGCGCGGCCUGGAAAGA 23 12424

BCLllA-11830 + AGGAGCCCGCGCGGCCUGGAAAGA 24 12425

BCLllA-11831 + AAAAAAGAAAAAAAUAGA 18 12426

BCLllA-11832 + CAAAAAAGAAAAAAAUAGA 19 12427

BCLllA-11833 + U CAAAAAAG AAAAAAAU AG A 20 12428

BCLllA-11834 + UU CAAAAAAGAAAAAAAUAGA 21 12429

BCLllA-11835 + A U U CAAAAAAG A A A A AAA U AG A 22 12430

BCLllA-11836 + U A U U CAAAAAAG A A A A AAA U AG A 23 12431

BCLllA-11837 + U U AU U CAAAAAAGAAAAAAAUAGA 24 12432

BCLllA-11838 + CAGCUCCGCAGCGGGCGA 18 12433

BCLllA-11839 + ACAGCUCCGCAGCGGGCGA 19 12434

BCLllA-10044 + UACAGCUCCGCAGCGGGCGA 20 12435

BCLllA-11840 + U UACAGCUCCGCAGCGGGCGA 21 12436

BCLllA-11841 + GUUACAGCUCCGCAGCGGGCGA 22 12437

BCLllA-11842 + AGUUACAGCUCCGCAGCGGGCGA 23 12438

BCLllA-11843 + AAGUUACAGCUCCGCAGCGGGCGA 24 12439

BCLllA-11844 + GGAAACUUUGCCCGAGGA 18 12440

BCLllA-11845 + GGGAAACUUUGCCCGAGGA 19 12441

BCLllA-11846 + CGGGAAACUUUGCCCGAGGA 20 12442

BCLllA-11847 + UCGGGAAACUUUGCCCGAGGA 21 12443

BCLllA-11848 + CUCGGGAAACUU UGCCCGAGGA 22 12444

BCLllA-11849 + GCUCGGGAAACUU UGCCCGAGGA 23 12445

BCLllA-11850 + CGCUCGGGAAACUUUGCCCGAGGA 24 12446

BCLllA-11851 + AAGCGGCGGAAAGGAGGA 18 12447

BCLllA-11852 + AAAGCGGCGGAAAGGAGGA 19 12448

BCLllA-11853 + UAAAGCGGCGGAAAGGAGGA 20 12449

BCLllA-11854 + AUAAAGCGGCGGAAAGGAGGA 21 12450

BCLllA-11855 + AAUAAAGCGGCGGAAAGGAGGA 22 12451

BCLllA-11856 + AAA U A A AG CG G CG G A A AG G AG G A 23 12452 BCLllA-11857 + GAAAUAAAGCGGCGGAAAGGAGGA 24 12453

BCLllA-11858 + GAGAAAUAAAGCGGCGGA 18 12454

BCLllA-11859 + AGAGAAAUAAAGCGGCGGA 19 12455

BCLllA-11860 + AAGAGAAAUAAAGCGGCGGA 20 12456

BCLllA-11861 + AAAGAGAAAUAAAGCGGCGGA 21 12457

BCLllA-11862 + AAAAGAGAAAUAAAGCGGCGGA 22 12458

BCLllA-11863 + G A A A AG AG A A A U A A AG CG G CG G A 23 12459

BCLllA-11864 + CGAAAAGAGAAAUAAAGCGGCGGA 24 12460

BCLllA-11865 + UGGGGAAGCGCGGGCGGA 18 12461

BCLllA-11866 + CUGGGGAAGCGCGGGCGGA 19 12462

BCLllA-10048 + GCUGGGGAAGCGCGGGCGGA 20 12463

BCLllA-11867 + GGCUGGGGAAGCGCGGGCGGA 21 12464

BCLllA-11868 + GGGCUGGGGAAGCGCGGGCGGA 22 12465

BCLllA-11869 + CGGGCUGGGGAAGCGCGGGCGGA 23 12466

BCLllA-11870 + CCGGGCUGGGGAAGCGCGGGCGGA 24 12467

BCLllA-11871 + CCAAGGCCGAGCCAGGGA 18 12468

BCLllA-11872 + CCCAAGGCCGAGCCAGGGA 19 12469

BCLllA-11873 + CCCCAAGGCCGAGCCAGGGA 20 12470

BCLllA-11874 + CCCCCAAGGCCGAGCCAGGGA 21 12471

BCLllA-11875 + GCCCCCAAGGCCGAGCCAGGGA 22 12472

BCLllA-11876 + CGCCCCCAAGGCCGAGCCAGGGA 23 12473

BCLllA-11877 + GCGCCCCCAAGGCCGAGCCAGGGA 24 12474

BCLllA-11878 + CGGCCUGGAAAGAGGGGA 18 12475

BCLllA-11879 + GCGGCCUGGAAAGAGGGGA 19 12476

BCLllA-11880 + CGCGGCCUGGAAAGAGGGGA 20 12477

BCLllA-11881 + GCGCGGCCUGGAAAGAGGGGA 21 12478

BCLllA-11882 + CGCGCGGCCUGGAAAGAGGGGA 22 12479

BCLllA-11883 + CCGCGCGGCCUGGAAAGAGGGGA 23 12480

BCLllA-11884 + CCCGCGCGGCCUGGAAAGAGGGGA 24 12481

BCLllA-11885 + UGGCGGGGCGGGGGGGGA 18 12482

BCLllA-11886 + CUGGCGGGGCGGGGGGGGA 19 12483

BCLllA-11887 + ACUGGCGGGGCGGGGGGGGA 20 12484

BCLllA-11888 + AACUGGCGGGGCGGGGGGGGA 21 12485

BCLllA-11889 + AAACUGGCGGGGCGGGGGGGGA 22 12486

BCLllA-11890 + AAAACUGGCGGGGCGGGGGGGGA 23 12487

BCLllA-11891 + CAAAACUGGCGGGGCGGGGGGGGA 24 12488

BCLllA-11892 + GGGCGAGGGGAGGUGGGA 18 12489

BCLllA-11893 + CGGGCGAGGGGAGGUGGGA 19 12490

BCLllA-10052 + GCGGGCGAGGGGAGGUGGGA 20 12491

BCLllA-11894 + AGCGGGCGAGGGGAGGUGGGA 21 12492

BCLllA-11895 + CAGCGGGCGAGGGGAGGUGGGA 22 12493

BCLllA-11896 + GCAGCGGGCGAGGGGAGGUGGGA 23 12494 BCLllA-11897 + CGCAGCGGGCGAGGGGAGGUGGGA 24 12495

BCLllA-11898 + GAGCCCGCGCGGCCUGGA 18 12496

BCLllA-11899 + GGAGCCCGCGCGGCCUGGA 19 12497

BCLllA-11900 + AGGAGCCCGCGCGGCCUGGA 20 12498

BCLllA-11901 + CAGGAGCCCGCGCGGCCUGGA 21 12499

BCLllA-11902 + CCAGGAGCCCGCGCGGCCUGGA 22 12500

BCLllA-11903 + UCCAGGAGCCCGCGCGGCCUGGA 23 12501

BCLllA-11904 + CUCCAGGAGCCCGCGCGGCCUGGA 24 12502

BCLllA-11905 + CCCAUU UUCUUACGGUGA 18 12503

BCLllA-11906 + CCCCAUU UUCUUACGGUGA 19 12504

BCLllA-11907 + CCCCCAUUU UCUUACGGUGA 20 12505

BCLllA-11908 + CCCCCCAUUUUCUUACGGUGA 21 12506

BCLllA-11909 + CCCCCCCAUUUUCUUACGGUGA 22 12507

BCLllA-11910 + ACCCCCCCAUUU UCUUACGGUGA 23 12508

BCLllA-11911 + UACCCCCCCAUU UUCUUACGGUGA 24 12509

BCLllA-11912 + GAGGGAGCGCACGGCAAC 18 12510

BCLllA-11913 + GGAGGGAGCGCACGGCAAC 19 12511

BCLllA-11914 + GGGAGGGAGCGCACGGCAAC 20 12512

BCLllA-11915 + UGGGAGGGAGCGCACGGCAAC 21 12513

BCLllA-11916 + GUGGGAGGGAGCGCACGGCAAC 22 12514

BCLllA-11917 + GGUGGGAGGGAGCGCACGGCAAC 23 12515

BCLllA-11918 + AGGUGGGAGGGAGCGCACGGCAAC 24 12516

BCLllA-10612 + CUGCUCCCCCCCACACAC 18 12517

BCLllA-10613 + CCUGCUCCCCCCCACACAC 19 12518

BCLllA-10614 + CCCUGCUCCCCCCCACACAC 20 12519

BCLllA-10615 + GCCCUGCUCCCCCCCACACAC 21 12520

BCLllA-10616 + CGCCCUGCUCCCCCCCACACAC 22 12521

BCLllA-10617 + GCGCCCUGCUCCCCCCCACACAC 23 12522

BCLllA-10618 + UGCGCCCUGCUCCCCCCCACACAC 24 12523

BCLllA-11919 + AAUAGAGCGAGAGUGCAC 18 12524

BCLllA-11920 + AAAUAGAGCGAGAGUGCAC 19 12525

BCLllA-10059 + AAAAUAGAGCGAGAGUGCAC 20 12526

BCLllA-11921 + AAAAAUAGAGCGAGAGUGCAC 21 12527

BCLllA-11922 + AAAAAAUAGAGCGAGAGUGCAC 22 12528

BCLllA-11923 + AAAAAAAU AG AG CG AG AG UG CAC 23 12529

BCLllA-11924 + GAAAAAAAUAGAGCGAGAGUGCAC 24 12530

BCLllA-11925 + ACAGCAAAGAAAAAUCAC 18 12531

BCLllA-11926 + GACAGCAAAGAAAAAUCAC 19 12532

BCLllA-11927 + G G AC AG CAAAG AAAAAU CAC 20 12533

BCLllA-11928 + AGGACAGCAAAGAAAAAUCAC 21 12534

BCLllA-11929 + GAGGACAG CAAAG AAAAAU CAC 22 12535

BCLllA-11930 + AG AG G AC AG CAAAG AAAAAU CAC 23 12536 BCLllA-11931 + GAGAGGACAGCAAAGAAAAAUCAC 24 12537

BCLllA-11932 + CAAGGCCGAGCCAGGGAC 18 12538

BCLllA-11933 + CCAAGGCCGAGCCAGGGAC 19 12539

BCLllA-10063 + CCCAAGGCCGAGCCAGGGAC 20 12540

BCLllA-11934 + CCCCAAGGCCGAGCCAGGGAC 21 12541

BCLllA-11935 + CCCCCAAGGCCGAGCCAGGGAC 22 12542

BCLllA-11936 + GCCCCCAAGGCCGAGCCAGGGAC 23 12543

BCLllA-11937 + CGCCCCCAAGGCCGAGCCAGGGAC 24 12544

BCLllA-11938 + GGCCUGGAAAGAGGGGAC 18 12545

BCLllA-11939 + CGGCCUGGAAAGAGGGGAC 19 12546

BCLllA-10064 + GCGGCCUGGAAAGAGGGGAC 20 12547

BCLllA-11940 + CGCGGCCUGGAAAGAGGGGAC 21 12548

BCLllA-11941 + GCGCGGCCUGGAAAGAGGGGAC 22 12549

BCLllA-11942 + CGCGCGGCCUGGAAAGAGGGGAC 23 12550

BCLllA-11943 + CCGCGCGGCCUGGAAAGAGGGGAC 24 12551

BCLllA-11944 + AUAGAGCGAGAGUGCACC 18 12552

BCLllA-11945 + AAUAGAGCGAGAGUGCACC 19 12553

BCLllA-10067 + AAAUAGAGCGAGAGUGCACC 20 12554

BCLllA-11946 + AAAAUAGAGCGAGAGUGCACC 21 12555

BCLllA-11947 + AAAAAUAGAGCGAGAGUGCACC 22 12556

BCLllA-11948 + AAAAAAUAGAGCGAGAGUGCACC 23 12557

BCLllA-11949 + AAAAAAAUAGAGCGAGAGUGCACC 24 12558

BCLllA-11950 + AAGGCCGAGCCAGGGACC 18 12559

BCLllA-11951 + CAAGGCCGAGCCAGGGACC 19 12560

BCLllA-10068 + CCAAGGCCGAGCCAGGGACC 20 12561

BCLllA-11952 + CCCAAGGCCGAGCCAGGGACC 21 12562

BCLllA-11953 + CCCCAAGGCCGAGCCAGGGACC 22 12563

BCLllA-11954 + CCCCCAAGGCCGAGCCAGGGACC 23 12564

BCLllA-11955 + GCCCCCAAGGCCGAGCCAGGGACC 24 12565

BCLllA-11956 + GCCUGGAAAGAGGGGACC 18 12566

BCLllA-11957 + GGCCUGGAAAGAGGGGACC 19 12567

BCLllA-10069 + CGGCCUGGAAAGAGGGGACC 20 12568

BCLllA-11958 + GCGGCCUGGAAAGAGGGGACC 21 12569

BCLllA-11959 + CGCGGCCUGGAAAGAGGGGACC 22 12570

BCLllA-11960 + GCGCGGCCUGGAAAGAGGGGACC 23 12571

BCLllA-11961 + CGCGCGGCCUGGAAAGAGGGGACC 24 12572

BCLllA-11962 + CCCGCUGCACACUUGACC 18 12573

BCLllA-11963 + UCCCGCUGCACACU UGACC 19 12574

BCLllA-11964 + CUCCCGCUGCACACU UGACC 20 12575

BCLllA-11965 + CCUCCCGCUGCACACUUGACC 21 12576

BCLllA-11966 + UCCUCCCGCUGCACACU UGACC 22 12577

BCLllA-11967 + U UCCUCCCGCUGCACACUUGACC 23 12578 BCLllA-11968 + U UUCCUCCCGCUGCACACUUGACC 24 12579

BCLllA-11969 + CGGCGCAGGCCGGGGCCC 18 12580

BCLllA-11970 + GCGGCGCAGGCCGGGGCCC 19 12581

BCLllA-11971 + GGCGGCGCAGGCCGGGGCCC 20 12582

BCLllA-11972 + AGGCGGCGCAGGCCGGGGCCC 21 12583

BCLllA-11973 + CAGGCGGCGCAGGCCGGGGCCC 22 12584

BCLllA-11974 + GCAGGCGGCGCAGGCCGGGGCCC 23 12585

BCLllA-11975 + GGCAGGCGGCGCAGGCCGGGGCCC 24 12586

BCLllA-11976 + GCUCGGGAAACUU UGCCC 18 12587

BCLllA-11977 + CGCUCGGGAAACUUUGCCC 19 12588

BCLllA-11978 + GCGCUCGGGAAACUUUGCCC 20 12589

BCLllA-11979 + UGCGCUCGGGAAACUUUGCCC 21 12590

BCLllA-11980 + CUGCGCUCGGGAAACUUUGCCC 22 12591

BCLllA-11981 + GCUGCGCUCGGGAAACUUUGCCC 23 12592

BCLllA-11982 + GGCUGCGCUCGGGAAACUUUGCCC 24 12593

BCLllA-11983 + UCUCACCUCUUU UCUCCC 18 12594

BCLllA-11984 + GUCUCACCUCUUUUCUCCC 19 12595

BCLllA-10081 + AGUCUCACCUCUUUUCUCCC 20 12596

BCLllA-11985 + CAGUCUCACCUCUUUUCUCCC 21 12597

BCLllA-11986 + CCAGUCUCACCUCUUUUCUCCC 22 12598

BCLllA-11987 + GCCAGUCUCACCUCUUU UCUCCC 23 12599

BCLllA-11988 + AGCCAGUCUCACCUCUUUUCUCCC 24 12600

BCLllA-11989 + GGGGCCGAAGU A A A AG C C 18 12601

BCLllA-11990 + AGGGGCCGAAGUAAAAGCC 19 12602

BCLllA-11991 + CAGGGGCCGAAGUAAAAGCC 20 12603

BCLllA-11992 + CCAGGGGCCGAAGUAAAAGCC 21 12604

BCLllA-11993 + GCCAGGGGCCGAAGUAAAAGCC 22 12605

BCLllA-11994 + CGCCAGGGGCCGAAGUAAAAGCC 23 12606

BCLllA-11995 + ACGCCAGGGGCCGAAGUAAAAGCC 24 12607

BCLllA-11996 + CACCGGGAGGCUGCAGCC 18 12608

BCLllA-11997 + GCACCGGGAGGCUGCAGCC 19 12609

BCLllA-11998 + UGCACCGGGAGGCUGCAGCC 20 12610

BCLllA-11999 + GUGCACCGGGAGGCUGCAGCC 21 12611

BCLllA-12000 + AGUGCACCGGGAGGCUGCAGCC 22 12612

BCLllA-12001 + GAGUGCACCGGGAGGCUGCAGCC 23 12613

BCLllA-12002 + AGAGUGCACCGGGAGGCUGCAGCC 24 12614

BCLllA-12003 + CGCCCCCAAGGCCGAGCC 18 12615

BCLllA-12004 + GCGCCCCCAAGGCCGAGCC 19 12616

BCLllA-10085 + GGCGCCCCCAAGGCCGAGCC 20 12617

BCLllA-12005 + GGGCGCCCCCAAGGCCGAGCC 21 12618

BCLllA-12006 + AGGGCGCCCCCAAGGCCGAGCC 22 12619

BCLllA-12007 + GAGGGCGCCCCCAAGGCCGAGCC 23 12620 BCLllA-12008 + CGAGGGCGCCCCCAAGGCCGAGCC 24 12621

BCLllA-12009 + UCCCCGCGUGUGGACGCC 18 12622

BCLllA-12010 + CUCCCCGCGUGUGGACGCC 19 12623

BCLllA-10086 + GCUCCCCGCGUGUGGACGCC 20 12624

BCLllA-12011 + CGCUCCCCGCGUGUGGACGCC 21 12625

BCLllA-12012 + UCGCUCCCCGCGUGUGGACGCC 22 12626

BCLllA-12013 + CUCGCUCCCCGCGUGUGGACGCC 23 12627

BCLllA-12014 + GCUCGCUCCCCGCGUGUGGACGCC 24 12628

BCLllA-12015 + CGCGGACUCAGGAGCGCC 18 12629

BCLllA-12016 + CCGCGGACUCAGGAGCGCC 19 12630

BCLllA-10087 + UCCGCGGACUCAGGAGCGCC 20 12631

BCLllA-12017 + CUCCGCGGACUCAGGAGCGCC 21 12632

BCLllA-12018 + ACUCCGCGGACUCAGGAGCGCC 22 12633

BCLllA-12019 + GACUCCGCGGACUCAGGAGCGCC 23 12634

BCLllA-12020 + CGACUCCGCGGACUCAGGAGCGCC 24 12635

BCLllA-12021 + CCAGGAGCCCGCGCGGCC 18 12636

BCLllA-12022 + UCCAGGAGCCCGCGCGGCC 19 12637

BCLllA-10089 + CUCCAGGAGCCCGCGCGGCC 20 12638

BCLllA-12023 + UCUCCAGGAGCCCGCGCGGCC 21 12639

BCLllA-12024 + GUCUCCAGGAGCCCGCGCGGCC 22 12640

BCLllA-12025 + AGUCUCCAGGAGCCCGCGCGGCC 23 12641

BCLllA-12026 + AAGUCUCCAGGAGCCCGCGCGGCC 24 12642

BCLllA-12027 + GGCCCCUCUCCCGACUCC 18 12643

BCLllA-12028 + CGGCCCCUCUCCCGACUCC 19 12644

BCLllA-12029 + GCGGCCCCUCUCCCGACUCC 20 12645

BCLllA-12030 + CGCGGCCCCUCUCCCGACUCC 21 12646

BCLllA-12031 + CCGCGGCCCCUCUCCCGACUCC 22 12647

BCLllA-12032 + GCCGCGGCCCCUCUCCCGACUCC 23 12648

BCLllA-12033 + CGCCGCGGCCCCUCUCCCGACUCC 24 12649

BCLllA-12034 + GGCAGCGCCCAAGUCUCC 18 12650

BCLllA-12035 + GGGCAGCGCCCAAGUCUCC 19 12651

BCLllA-10093 + AGGGCAGCGCCCAAGUCUCC 20 12652

BCLllA-12036 + AAGGGCAGCGCCCAAGUCUCC 21 12653

BCLllA-12037 + GAAGGGCAGCGCCCAAGUCUCC 22 12654

BCLllA-12038 + GGAAGGGCAGCGCCCAAGUCUCC 23 12655

BCLllA-12039 + CGGAAGGGCAGCGCCCAAGUCUCC 24 12656

BCLllA-12040 + GUCUCACCUCUU UUCUCC 18 12657

BCLllA-12041 + AGUCUCACCUCUUUUCUCC 19 12658

BCLllA-12042 + CAGUCUCACCUCU UUUCUCC 20 12659

BCLllA-12043 + CCAGUCUCACCUCUUUUCUCC 21 12660

BCLllA-12044 + GCCAGUCUCACCUCUUUUCUCC 22 12661

BCLllA-12045 + AGCCAGUCUCACCUCUU UUCUCC 23 12662 BCLllA-12046 + AAGCCAGUCUCACCUCU UUUCUCC 24 12663

BCLllA-12047 + CGGCGCGGGAGGGCAAGC 18 12664

BCLllA-12048 + GCGGCGCGGGAGGGCAAGC 19 12665

BCLllA-12049 + GGCGGCGCGGGAGGGCAAGC 20 12666

BCLllA-12050 + GCCCCGGGCUGGGGAAGC 18 12667

BCLllA-12051 + AGCCCCGGGCUGGGGAAGC 19 12668

BCLllA-12052 + CAGCCCCGGGCUGGGGAAGC 20 12669

BCLllA-12053 + GCAGCCCCGGGCUGGGGAAGC 21 12670

BCLllA-12054 + UGCAGCCCCGGGCUGGGGAAGC 22 12671

BCLllA-12055 + CUGCAGCCCCGGGCUGGGGAAGC 23 12672

BCLllA-12056 + GCUGCAGCCCCGGGCUGGGGAAGC 24 12673

BCLllA-12057 + GCGCCCCCAAGGCCGAGC 18 12674

BCLllA-12058 + GGCGCCCCCAAGGCCGAGC 19 12675

BCLllA-12059 + GGGCGCCCCCAAGGCCGAGC 20 12676

BCLllA-12060 + AGGGCGCCCCCAAGGCCGAGC 21 12677

BCLllA-12061 + GAGGGCGCCCCCAAGGCCGAGC 22 12678

BCLllA-12062 + CGAGGGCGCCCCCAAGGCCGAGC 23 12679

BCLllA-12063 + CCGAGGGCGCCCCCAAGGCCGAGC 24 12680

BCLllA-12064 + CUCCCCGCGUGUGGACGC 18 12681

BCLllA-12065 + GCUCCCCGCGUGUGGACGC 19 12682

BCLllA-12066 + CGCUCCCCGCGUGUGGACGC 20 12683

BCLllA-12067 + UCGCUCCCCGCGUGUGGACGC 21 12684

BCLllA-12068 + CUCGCUCCCCGCGUGUGGACGC 22 12685

BCLllA-12069 + GCUCGCUCCCCGCGUGUGGACGC 23 12686

BCLllA-12070 + CGCUCGCUCCCCGCGUGUGGACGC 24 12687

BCLllA-12071 + GCGCGGGAGGGCAAGCGC 18 12688

BCLllA-12072 + GGCGCGGGAGGGCAAGCGC 19 12689

BCLllA-12073 + CGGCGCGGGAGGGCAAGCGC 20 12690

BCLllA-12074 + CCGCGGACUCAGGAGCGC 18 12691

BCLllA-12075 + UCCGCGGACUCAGGAGCGC 19 12692

BCLllA-10106 + CUCCGCGGACUCAGGAGCGC 20 12693

BCLllA-12076 + ACUCCGCGGACUCAGGAGCGC 21 12694

BCLllA-12077 + GACUCCGCGGACUCAGGAGCGC 22 12695

BCLllA-12078 + CGACUCCGCGGACUCAGGAGCGC 23 12696

BCLllA-12079 + CCGACUCCGCGGACUCAGGAGCGC 24 12697

BCLllA-12080 + CCGAGCCCGCGGCUGCGC 18 12698

BCLllA-12081 + CCCGAGCCCGCGGCUGCGC 19 12699

BCLllA-12082 + CCCCGAGCCCGCGGCUGCGC 20 12700

BCLllA-12083 + GCCCCGAGCCCGCGGCUGCGC 21 12701

BCLllA-12084 + AGCCCCGAGCCCGCGGCUGCGC 22 12702

BCLllA-12085 + AAGCCCCGAGCCCGCGGCUGCGC 23 12703

BCLllA-12086 + AAAGCCCCGAGCCCGCGGCUGCGC 24 12704 BCLllA-12087 + GAGGCAGGCGGCGCAGGC 18 12705

BCLllA-12088 + AGAGGCAGGCGGCGCAGGC 19 12706

BCLllA-10110 + GAGAGGCAGGCGGCGCAGGC 20 12707

BCLllA-12089 + GGAGAGGCAGGCGGCGCAGGC 21 12708

BCLllA-12090 + GGGAGAGGCAGGCGGCGCAGGC 22 12709

BCLllA-12091 + GGGGAGAGGCAGGCGGCGCAGGC 23 12710

BCLllA-12092 + CGGGGAGAGGCAGGCGGCGCAGGC 24 12711

BCLllA-12093 + UCCAGGAGCCCGCGCGGC 18 12712

BCLllA-12094 + CUCCAGGAGCCCGCGCGGC 19 12713

BCLllA-12095 + UCUCCAGGAGCCCGCGCGGC 20 12714

BCLllA-12096 + GUCUCCAGGAGCCCGCGCGGC 21 12715

BCLllA-12097 + AGUCUCCAGGAGCCCGCGCGGC 22 12716

BCLllA-12098 + AAGUCUCCAGGAGCCCGCGCGGC 23 12717

BCLllA-12099 + CAAGUCUCCAGGAGCCCGCGCGGC 24 12718

BCLllA-12100 + GAGGCUGCAGCCCCGGGC 18 12719

BCLllA-12101 + GGAGGCUGCAGCCCCGGGC 19 12720

BCLllA-10115 + GGGAGGCUGCAGCCCCGGGC 20 12721

BCLllA-12102 + CGGGAGGCUGCAGCCCCGGGC 21 12722

BCLllA-12103 + CCGGGAGGCUGCAGCCCCGGGC 22 12723

BCLllA-12104 + ACCGGGAGGCUGCAGCCCCGGGC 23 12724

BCLllA-12105 + CACCGGGAGGCUGCAGCCCCGGGC 24 12725

BCLllA-12106 + UACAGCUCCGCAGCGGGC 18 12726

BCLllA-12107 + U UACAGCUCCGCAGCGGGC 19 12727

BCLllA-12108 + GUUACAGCUCCGCAGCGGGC 20 12728

BCLllA-12109 + AGUUACAGCUCCGCAGCGGGC 21 12729

BCLllA-12110 + AAGUUACAGCUCCGCAGCGGGC 22 12730

BCLllA-12111 + CAAGUUACAGCUCCGCAGCGGGC 23 12731

BCLllA-12112 + CCAAGUUACAGCUCCGCAGCGGGC 24 12732

BCLllA-12113 + GGCGGCGCAGGCCGGGGC 18 12733

BCLllA-12114 + AGGCGGCGCAGGCCGGGGC 19 12734

BCLllA-12115 + CAGGCGGCGCAGGCCGGGGC 20 12735

BCLllA-12116 + GCAGGCGGCGCAGGCCGGGGC 21 12736

BCLllA-12117 + GGCAGGCGGCGCAGGCCGGGGC 22 12737

BCLllA-12118 + AGGCAGGCGGCGCAGGCCGGGGC 23 12738

BCLllA-12119 + GAGGCAGGCGGCGCAGGCCGGGGC 24 12739

BCLllA-12120 + U UGCAAAACUGGCGGGGC 18 12740

BCLllA-12121 + UUUGCAAAACUGGCGGGGC 19 12741

BCLllA-10116 + UUUUGCAAAACUGGCGGGGC 20 12742

BCLllA-12122 + AUUUUGCAAAACUGGCGGGGC 21 12743

BCLllA-12123 + UAUUUUGCAAAACUGGCGGGGC 22 12744

BCLllA-12124 + U UAUUUUGCAAAACUGGCGGGGC 23 12745

BCLllA-12125 + AUUAUUUUGCAAAACUGGCGGGGC 24 12746 BCLllA-12126 + CAAACACCCACCUCUGGC 18 12747

BCLllA-12127 + ACAAACACCCACCUCUGGC 19 12748

BCLllA-10118 + GACAAACACCCACCUCUGGC 20 12749

BCLllA-12128 + GGACAAACACCCACCUCUGGC 21 12750

BCLllA-12129 + GGGACAAACACCCACCUCUGGC 22 12751

BCLllA-12130 + CGGGACAAACACCCACCUCUGGC 23 12752

BCLllA-12131 + GCGGGACAAACACCCACCUCUGGC 24 12753

BCLllA-12132 + GCGCUCGGGAAACUUUGC 18 12754

BCLllA-12133 + UGCGCUCGGGAAACUUUGC 19 12755

BCLllA-12134 + CUGCGCUCGGGAAACUU UGC 20 12756

BCLllA-12135 + GCUGCGCUCGGGAAACU UUGC 21 12757

BCLllA-12136 + GGCUGCGCUCGGGAAACUUUGC 22 12758

BCLllA-12137 + CGGCUGCGCUCGGGAAACUUUGC 23 12759

BCLllA-12138 + GCGGCUGCGCUCGGGAAACUUUGC 24 12760

BCLllA-12139 + UCCCGACUCCGCGGACUC 18 12761

BCLllA-12140 + CUCCCGACUCCGCGGACUC 19 12762

BCLllA-10122 + UCUCCCGACUCCGCGGACUC 20 12763

BCLllA-12141 + CUCUCCCGACUCCGCGGACUC 21 12764

BCLllA-12142 + CCUCUCCCGACUCCGCGGACUC 22 12765

BCLllA-12143 + CCCUCUCCCGACUCCGCGGACUC 23 12766

BCLllA-12144 + CCCCUCUCCCGACUCCGCGGACUC 24 12767

BCLllA-12145 + GAGCCCGCGGCUGCGCUC 18 12768

BCLllA-12146 + CGAGCCCGCGGCUGCGCUC 19 12769

BCLllA-10126 + CCGAGCCCGCGGCUGCGCUC 20 12770

BCLllA-12147 + CCCGAGCCCGCGGCUGCGCUC 21 12771

BCLllA-12148 + CCCCGAGCCCGCGGCUGCGCUC 22 12772

BCLllA-12149 + GCCCCGAGCCCGCGGCUGCGCUC 23 12773

BCLllA-12150 + AGCCCCGAGCCCGCGGCUGCGCUC 24 12774

BCLllA-12151 + AGCCAGGUAGAGUUGCUC 18 12775

BCLllA-12152 + AAGCCAGGUAGAGUUGCUC 19 12776

BCLllA-12153 + GAAGCCAGGUAGAGUUGCUC 20 12777

BCLllA-12154 + GGAAGCCAGGUAGAGUUGCUC 21 12778

BCLllA-12155 + GGGAAGCCAGGUAGAGUUGCUC 22 12779

BCLllA-12156 + AGGGAAGCCAGGUAGAGUUGCUC 23 12780

BCLllA-12157 + GAGGGAAGCCAGGUAGAGUUGCUC 24 12781

BCLllA-12158 + GGGCAGCGCCCAAGUCUC 18 12782

BCLllA-12159 + AGGGCAGCGCCCAAGUCUC 19 12783

BCLllA-12160 + AAGGGCAGCGCCCAAGUCUC 20 12784

BCLllA-12161 + GAAGGGCAGCGCCCAAGUCUC 21 12785

BCLllA-12162 + GGAAGGGCAGCGCCCAAGUCUC 22 12786

BCLllA-12163 + CGGAAGGGCAGCGCCCAAGUCUC 23 12787

BCLllA-12164 + CCGGAAGGGCAGCGCCCAAGUCUC 24 12788 BCLllA-12165 + U UUGGAGGGCUGCGGGUC 18 12789

BCLllA-12166 + GUUUGGAGGGCUGCGGGUC 19 12790

BCLllA-10129 + AGUUUGGAGGGCUGCGGGUC 20 12791

BCLllA-12167 + AAGUUUGGAGGGCUGCGGGUC 21 12792

BCLllA-12168 + UAAGUUUGGAGGGCUGCGGGUC 22 12793

BCLllA-12169 + CU AAGUUUGGAGGGCUGCGGGUC 23 12794

BCLllA-12170 + CCUAAGUUUGGAGGGCUGCGGGUC 24 12795

BCLllA-12171 + CGGCGGAAAGGAGGAAAG 18 12796

BCLllA-12172 + GCGGCGGAAAGGAGGAAAG 19 12797

BCLllA-10136 + AGCGGCGGAAAGGAGGAAAG 20 12798

BCLllA-12173 + AAGCGGCGG A A AG G AG G A A AG 21 12799

BCLllA-12174 + A A AG CG G CG G A A AG G AG G A A AG 22 12800

BCLllA-12175 + UAAAGCGGCGGAAAGGAGGAAAG 23 12801

BCLllA-12176 + AUAAAGCGGCGGAAAGGAGGAAAG 24 12802

BCLllA-12177 + AAAUAAAGCGGCGGAAAG 18 12803

BCLllA-12178 + G AAA U A A AG CG G CG G A A AG 19 12804

BCLllA-12179 + AGAAAUAAAGCGGCGGAAAG 20 12805

BCLllA-12180 + GAGAAAUAAAGCGGCGGAAAG 21 12806

BCLllA-12181 + AG AG A A A U A A AG CG G CG G A A AG 22 12807

BCLllA-12182 + AAGAGAAAUAAAGCGGCGGAAAG 23 12808

BCLllA-12183 + AAAGAGAAAUAAAGCGGCGGAAAG 24 12809

BCLllA-12184 + CCCGCGCGGCCUGGAAAG 18 12810

BCLllA-12185 + GCCCGCGCGGCCUGGAAAG 19 12811

BCLllA-10137 + AGCCCGCGCGGCCUGGAAAG 20 12812

BCLllA-12186 + GAGCCCGCGCGGCCUGGAAAG 21 12813

BCLllA-12187 + GGAGCCCGCGCGGCCUGGAAAG 22 12814

BCLllA-12188 + AGGAGCCCGCGCGGCCUGGAAAG 23 12815

BCLllA-12189 + CAGGAGCCCGCGCGGCCUGGAAAG 24 12816

BCLllA-12190 + AAGAAAAAUCACCCGAAG 18 12817

BCLllA-12191 + AAAGAAAAAUCACCCGAAG 19 12818

BCLllA-12192 + CAAAGAAAAAUCACCCGAAG 20 12819

BCLllA-12193 + GCAAAGAAAAAUCACCCGAAG 21 12820

BCLllA-12194 + AGCAAAGAAAAAUCACCCGAAG 22 12821

BCLllA-12195 + CAGCAAAGAAAAAUCACCCGAAG 23 12822

BCLllA-12196 + ACAG CAAAGAAAAAUCACCCGAAG 24 12823

BCLllA-12197 + AG C CG G C A C A A A AG G C AG 18 12824

BCLllA-12198 + GAG CCGG CACAAAAGG CAG 19 12825

BCLllA-10144 + GG AG CCGG CACAAAAGG CAG 20 12826

BCLllA-12199 + AGGAGCCGGCACAAAAGGCAG 21 12827

BCLllA-12200 + GAG GAG CCGG CAC AAAAG G CAG 22 12828

BCLllA-12201 + CGAGGAGCCGGCACAAAAGGCAG 23 12829

BCLllA-12202 + G CG AGG AG CCGG CACAAAAGG CAG 24 12830 BCLllA-12203 + GCGGAAAGGAGGAAAGAG 18 12831

BCLllA-12204 + GGCGGAAAGGAGGAAAGAG 19 12832

BCLllA-12205 + CGGCGGAAAGGAGGAAAGAG 20 12833

BCLllA-12206 + GCGGCGGAAAGGAGGAAAGAG 21 12834

BCLllA-12207 + AGCGGCGGAAAGGAGGAAAGAG 22 12835

BCLllA-12208 + AAGCGGCGGAAAGGAGGAAAGAG 23 12836

BCLllA-12209 + A AAG CGG CG G AAAG GAG G AAAG AG 24 12837

BCLllA-12210 + AUCACCCGAAGUUGAGAG 18 12838

BCLllA-12211 + AAU CACCCG AAG U UG AG AG 19 12839

BCLllA-12212 + AAAUCACCCGAAGUUGAGAG 20 12840

BCLllA-12213 + AAAAU CACCCG AAG U UG AG AG 21 12841

BCLllA-12214 + AAAAAUCACCCGAAGUUGAGAG 22 12842

BCLllA-12215 + G AAAAAU CACCCG AAG U UG AG AG 23 12843

BCLllA-12216 + AG AAAAAU CACCCG AAG U UG AG AG 24 12844

BCLllA-12217 + CGGGAAACUUUGCCCGAG 18 12845

BCLllA-12218 + UCGGGAAACUUUGCCCGAG 19 12846

BCLllA-12219 + CUCGGGAAACUU UGCCCGAG 20 12847

BCLllA-12220 + GCUCGGGAAACUU UGCCCGAG 21 12848

BCLllA-12221 + CGCUCGGGAAACUUUGCCCGAG 22 12849

BCLllA-12222 + GCGCUCGGGAAACUUUGCCCGAG 23 12850

BCLllA-12223 + UGCGCUCGGGAAACUUUGCCCGAG 24 12851

BCLllA-12224 + AGCUCCGCAGCGGGCGAG 18 12852

BCLllA-12225 + CAGCUCCGCAGCGGGCGAG 19 12853

BCLllA-10148 + ACAGCUCCGCAGCGGGCGAG 20 12854

BCLllA-12226 + UACAGCUCCGCAGCGGGCGAG 21 12855

BCLllA-12227 + U UACAGCUCCGCAGCGGGCGAG 22 12856

BCLllA-12228 + GUUACAGCUCCGCAGCGGGCGAG 23 12857

BCLllA-12229 + AGUUACAGCUCCGCAGCGGGCGAG 24 12858

BCLllA-12230 + CGCAGCGGGCGAGGGGAG 18 12859

BCLllA-12231 + CCGCAGCGGGCGAGGGGAG 19 12860

BCLllA-12232 + UCCGCAGCGGGCGAGGGGAG 20 12861

BCLllA-12233 + CUCCGCAGCGGGCGAGGGGAG 21 12862

BCLllA-12234 + GCUCCGCAGCGGGCGAGGGGAG 22 12863

BCLllA-12235 + AGCUCCGCAGCGGGCGAGGGGAG 23 12864

BCLllA-12236 + CAGCUCCGCAGCGGGCGAGGGGAG 24 12865

BCLllA-12237 + CCAUUUUCUUACGGUGAG 18 12866

BCLllA-12238 + CCCAUUUUCUUACGGUGAG 19 12867

BCLllA-10154 + CCCCAUU UUCUUACGGUGAG 20 12868

BCLllA-12239 + CCCCCAUUUUCUUACGGUGAG 21 12869

BCLllA-12240 + CCCCCCAUUUUCUUACGGUGAG 22 12870

BCLllA-12241 + CCCCCCCAUUUUCUUACGGUGAG 23 12871

BCLllA-12242 + ACCCCCCCAUUU UCUUACGGUGAG 24 12872 BCLllA-12243 + CCUGGAAAGAGGGGACCG 18 12873

BCLllA-12244 + GCCUGGAAAGAGGGGACCG 19 12874

BCLllA-10159 + GGCCUGGAAAGAGGGGACCG 20 12875

BCLllA-12245 + CGGCCUGGAAAGAGGGGACCG 21 12876

BCLllA-12246 + GCGGCCUGGAAAGAGGGGACCG 22 12877

BCLllA-12247 + CGCGGCCUGGAAAGAGGGGACCG 23 12878

BCLllA-12248 + GCGCGGCCUGGAAAGAGGGGACCG 24 12879

BCLllA-12249 + CUCGGGAAACUUUGCCCG 18 12880

BCLllA-12250 + GCUCGGGAAACUUUGCCCG 19 12881

BCLllA-10163 + CGCUCGGGAAACUUUGCCCG 20 12882

BCLllA-12251 + GCGCUCGGGAAACUUUGCCCG 21 12883

BCLllA-12252 + UGCGCUCGGGAAACUUUGCCCG 22 12884

BCLllA-12253 + CUGCGCUCGGGAAACUU UGCCCG 23 12885

BCLllA-12254 + GCUGCGCUCGGGAAACUUUGCCCG 24 12886

BCLllA-12255 + G AAAAG AG AAAU AAAG CG 18 12887

BCLllA-12256 + CGAAAAGAGAAAUAAAGCG 19 12888

BCLllA-12257 + UCGAAAAGAGAAAUAAAGCG 20 12889

BCLllA-12258 + UU CGAAAAGAGAAAUAAAGCG 21 12890

BCLllA-12259 + UU UCGAAAAGAGAAAUAAAGCG 22 12891

BCLllA-12260 + U U U U CG AAAAG AG AAAU AAAG CG 23 12892

BCLllA-12261 + C U U U U CG AAAAG AG AAA U AAAG CG 24 12893

BCLllA-12262 + UCCGCGGACUCAGGAGCG 18 12894

BCLllA-12263 + CUCCGCGGACUCAGGAGCG 19 12895

BCLllA-12264 + ACUCCGCGGACUCAGGAGCG 20 12896

BCLllA-12265 + GACUCCGCGGACUCAGGAGCG 21 12897

BCLllA-12266 + CGACUCCGCGGACUCAGGAGCG 22 12898

BCLllA-12267 + CCGACUCCGCGGACUCAGGAGCG 23 12899

BCLllA-12268 + CCCGACUCCGCGGACUCAGGAGCG 24 12900

BCLllA-12269 + CGCGGGAGGGCAAGCGCG 18 12901

BCLllA-12270 + GCGCGGGAGGGCAAGCGCG 19 12902

BCLllA-10178 + GGCGCGGGAGGGCAAGCGCG 20 12903

BCLllA-12271 + ACAGCUCCGCAGCGGGCG 18 12904

BCLllA-12272 + UACAGCUCCGCAGCGGGCG 19 12905

BCLllA-10180 + U UACAGCUCCGCAGCGGGCG 20 12906

BCLllA-12273 + GUUACAGCUCCGCAGCGGGCG 21 12907

BCLllA-12274 + AGUUACAGCUCCGCAGCGGGCG 22 12908

BCLllA-12275 + AAGUUACAGCUCCGCAGCGGGCG 23 12909

BCLllA-12276 + CAAGUUACAGCUCCGCAGCGGGCG 24 12910

BCLllA-12277 + GCUGGGGAAGCGCGGGCG 18 12911

BCLllA-12278 + GGCUGGGGAAGCGCGGGCG 19 12912

BCLllA-12279 + GGGCUGGGGAAGCGCGGGCG 20 12913

BCLllA-12280 + CGGGCUGGGGAAGCGCGGGCG 21 12914 BCLllA-12281 + CCGGGCUGGGGAAGCGCGGGCG 22 12915

BCLllA-12282 + CCCGGGCUGGGGAAGCGCGGGCG 23 12916

BCLllA-12283 + CCCCGGGCUGGGGAAGCGCGGGCG 24 12917

BCLllA-12284 + UGCAAAACUGGCGGGGCG 18 12918

BCLllA-12285 + U UGCAAAACUGGCGGGGCG 19 12919

BCLllA-10181 + UUUGCAAAACUGGCGGGGCG 20 12920

BCLllA-12286 + UUUUGCAAAACUGGCGGGGCG 21 12921

BCLllA-12287 + AUUUUGCAAAACUGGCGGGGCG 22 12922

BCLllA-12288 + UAUUUUGCAAAACUGGCGGGGCG 23 12923

BCLllA-12289 + UUAUUUUGCAAAACUGGCGGGGCG 24 12924

BCLllA-12290 + A A U A A AG CG G CG G A A AG G 18 12925

BCLllA-12291 + AAAUAAAGCGGCGGAAAGG 19 12926

BCLllA-10185 + GAAAUAAAGCGGCGGAAAGG 20 12927

BCLllA-12292 + AGAAAUAAAGCGGCGGAAAGG 21 12928

BCLllA-12293 + GAG AAA U A A AG CG G CG G A A AG G 22 12929

BCLllA-12294 + AG AG A A A U A A AG CG G CG G A A AG G 23 12930

BCLllA-12295 + AAGAGAAAUAAAGCGGCGGAAAGG 24 12931

BCLllA-12296 + CCGAGGGCGCCCCCAAGG 18 12932

BCLllA-12297 + CCCGAGGGCGCCCCCAAGG 19 12933

BCLllA-12298 + GCCCGAGGGCGCCCCCAAGG 20 12934

BCLllA-12299 + GGCCCGAGGGCGCCCCCAAGG 21 12935

BCLllA-12300 + GGGCCCGAGGGCGCCCCCAAGG 22 12936

BCLllA-12301 + GGGGCCCGAGGGCGCCCCCAAGG 23 12937

BCLllA-12302 + CGGGGCCCGAGGGCGCCCCCAAGG 24 12938

BCLllA-12303 + AGAGGCAGGCGGCGCAGG 18 12939

BCLllA-12304 + GAGAGGCAGGCGGCGCAGG 19 12940

BCLllA-12305 + GGAGAGGCAGGCGGCGCAGG 20 12941

BCLllA-12306 + GGGAGAGGCAGGCGGCGCAGG 21 12942

BCLllA-12307 + GGGGAGAGGCAGGCGGCGCAGG 22 12943

BCLllA-12308 + CGGGGAGAGGCAGGCGGCGCAGG 23 12944

BCLllA-12309 + CCGGGGAGAGGCAGGCGGCGCAGG 24 12945

BCLllA-12310 + GCAGCGGGCGAGGGGAGG 18 12946

BCLllA-12311 + CGCAGCGGGCGAGGGGAGG 19 12947

BCLllA-10190 + CCGCAGCGGGCGAGGGGAGG 20 12948

BCLllA-12312 + UCCGCAGCGGGCGAGGGGAGG 21 12949

BCLllA-12313 + CUCCGCAGCGGGCGAGGGGAGG 22 12950

BCLllA-12314 + GCUCCGCAGCGGGCGAGGGGAGG 23 12951

BCLllA-12315 + AGCUCCGCAGCGGGCGAGGGGAGG 24 12952

BCLllA-12316 + GGAGGGCUGCGGGUCCGG 18 12953

BCLllA-12317 + UGGAGGGCUGCGGGUCCGG 19 12954

BCLllA-12318 + U UGGAGGGCUGCGGGUCCGG 20 12955

BCLllA-12319 + U UUGGAGGGCUGCGGGUCCGG 21 12956 BCLllA-12320 + GUUUGGAGGGCUGCGGGUCCGG 22 12957

BCLllA-12321 + AGUUUGGAGGGCUGCGGGUCCGG 23 12958

BCLllA-12322 + AAGUUUGGAGGGCUGCGGGUCCGG 24 12959

BCLllA-12323 + AAAAGAGAAAUAAAGCGG 18 12960

BCLllA-12324 + G A A A AG AG AAA U A A AG CG G 19 12961

BCLllA-10193 + CGAAAAGAGAAAUAAAGCGG 20 12962

BCLllA-12325 + U CG A A A AG AG AAA U A A AG CG G 21 12963

BCLllA-12326 + U UCGAAAAGAGAAAUAAAGCGG 22 12964

BCLllA-12327 + U UUCGAAAAGAGAAAUAAAGCGG 23 12965

BCLllA-12328 + U U U U CGAAAAGAGAAAUAAAGCGG 24 12966

BCLllA-12329 + GUUACAGCUCCGCAGCGG 18 12967

BCLllA-12330 + AGUUACAGCUCCGCAGCGG 19 12968

BCLllA-12331 + AAGUUACAGCUCCGCAGCGG 20 12969

BCLllA-12332 + CAAGUUACAGCUCCGCAGCGG 21 12970

BCLllA-12333 + CCAAGUUACAGCUCCGCAGCGG 22 12971

BCLllA-12334 + UCCAAG U U ACAG C U CCG CAG CG G 23 12972

BCLllA-12335 + CUCCAAGUUACAGCUCCGCAGCGG 24 12973

BCLllA-12336 + CGGGCUGGGGAAGCGCGG 18 12974

BCLllA-12337 + CCGGGCUGGGGAAGCGCGG 19 12975

BCLllA-12338 + CCCGGGCUGGGGAAGCGCGG 20 12976

BCLllA-12339 + CCCCGGGCUGGGGAAGCGCGG 21 12977

BCLllA-12340 + GCCCCGGGCUGGGGAAGCGCGG 22 12978

BCLllA-12341 + AGCCCCGGGCUGGGGAAGCGCGG 23 12979

BCLllA-12342 + CAGCCCCGGGCUGGGGAAGCGCGG 24 12980

BCLllA-12343 + CUGGGGAAGCGCGGGCGG 18 12981

BCLllA-12344 + GCUGGGGAAGCGCGGGCGG 19 12982

BCLllA-10197 + GGCUGGGGAAGCGCGGGCGG 20 12983

BCLllA-12345 + GGGCUGGGGAAGCGCGGGCGG 21 12984

BCLllA-12346 + CGGGCUGGGGAAGCGCGGGCGG 22 12985

BCLllA-12347 + CCGGGCUGGGGAAGCGCGGGCGG 23 12986

BCLllA-12348 + CCCGGGCUGGGGAAGCGCGGGCGG 24 12987

BCLllA-12349 + GCAAAACUGGCGGGGCGG 18 12988

BCLllA-12350 + UGCAAAACUGGCGGGGCGG 19 12989

BCLllA-10198 + U UGCAAAACUGGCGGGGCGG 20 12990

BCLllA-12351 + U UUGCAAAACUGGCGGGGCGG 21 12991

BCLllA-12352 + U UUUGCAAAACUGGCGGGGCGG 22 12992

BCLllA-12353 + AUUUUGCAAAACUGGCGGGGCGG 23 12993

BCLllA-12354 + UAUUUUGCAAAACUGGCGGGGCGG 24 12994

BCLllA-12355 + UGGAAAGAGGGGACCGGG 18 12995

BCLllA-12356 + CUGGAAAGAGGGGACCGGG 19 12996

BCLllA-12357 + CCUGGAAAGAGGGGACCGGG 20 12997

BCLllA-12358 + GCCUGGAAAGAGGGGACCGGG 21 12998 BCLllA-12359 + GGCCUGGAAAGAGGGGACCGGG 22 12999

BCLllA-12360 + CGGCCUGGAAAGAGGGGACCGGG 23 13000

BCLllA-12361 + GCGGCCUGGAAAGAGGGGACCGGG 24 13001

BCLllA-12362 + GGAGGCUGCAGCCCCGGG 18 13002

BCLllA-12363 + GGGAGGCUGCAGCCCCGGG 19 13003

BCLllA-12364 + CGGGAGGCUGCAGCCCCGGG 20 13004

BCLllA-12365 + CCGGGAGGCUGCAGCCCCGGG 21 13005

BCLllA-12366 + ACCGGGAGGCUGCAGCCCCGGG 22 13006

BCLllA-12367 + CACCGGGAGGCUGCAGCCCCGGG 23 13007

BCLllA-12368 + GCACCGGGAGGCUGCAGCCCCGGG 24 13008

BCLllA-12369 + GGGCUGGGGAAGCGCGGG 18 13009

BCLllA-12370 + CGGGCUGGGGAAGCGCGGG 19 13010

BCLllA-10203 + CCGGGCUGGGGAAGCGCGGG 20 13011

BCLllA-12371 + CCCGGGCUGGGGAAGCGCGGG 21 13012

BCLllA-12372 + CCCCGGGCUGGGGAAGCGCGGG 22 13013

BCLllA-12373 + GCCCCGGGCUGGGGAAGCGCGGG 23 13014

BCLllA-12374 + AGCCCCGGGCUGGGGAAGCGCGGG 24 13015

BCLllA-12375 + CAAAACUGGCGGGGCGGG 18 13016

BCLllA-12376 + GCAAAACUGGCGGGGCGGG 19 13017

BCLllA-10204 + UGCAAAACUGGCGGGGCGGG 20 13018

BCLllA-12377 + UUGCAAAACUGGCGGGGCGGG 21 13019

BCLllA-12378 + U UUGCAAAACUGGCGGGGCGGG 22 13020

BCLllA-12379 + U UUUGCAAAACUGGCGGGGCGGG 23 13021

BCLllA-12380 + AUUUUGCAAAACUGGCGGGGCGGG 24 13022

BCLllA-12381 + UUUUGCAAAACUGGCGGG 18 13023

BCLllA-12382 + AUUUUGCAAAACUGGCGGG 19 13024

BCLllA-12383 + UAUUUUGCAAAACUGGCGGG 20 13025

BCLllA-12384 + U UAUUUUGCAAAACUGGCGGG 21 13026

BCLllA-12385 + AUUAUUUUGCAAAACUGGCGGG 22 13027

BCLllA-12386 + CAUUAUUUUGCAAAACUGGCGGG 23 13028

BCLllA-12387 + UCAUUAUUUUGCAAAACUGGCGGG 24 13029

BCLllA-12388 + GCGUGUGGACGCCAGGGG 18 13030

BCLllA-12389 + CGCGUGUGGACGCCAGGGG 19 13031

BCLllA-12390 + CCGCGUGUGGACGCCAGGGG 20 13032

BCLllA-12391 + CCCGCGUGUGGACGCCAGGGG 21 13033

BCLllA-12392 + CCCCGCGUGUGGACGCCAGGGG 22 13034

BCLllA-12393 + UCCCCGCGUGUGGACGCCAGGGG 23 13035

BCLllA-12394 + CUCCCCGCGUGUGGACGCCAGGGG 24 13036

BCLllA-12395 + AAAACUGGCGGGGCGGGG 18 13037

BCLllA-12396 + CAAAACUGGCGGGGCGGGG 19 13038

BCLllA-10207 + GCAAAACUGGCGGGGCGGGG 20 13039

BCLllA-12397 + UGCAAAACUGGCGGGGCGGGG 21 13040 BCLllA-12398 + UUGCAAAACUGGCGGGGCGGGG 22 13041

BCLllA-12399 + UUUGCAAAACUGGCGGGGCGGGG 23 13042

BCLllA-12400 + UUUUGCAAAACUGGCGGGGCGGGG 24 13043

BCLllA-12401 + U UUGCAAAACUGGCGGGG 18 13044

BCLllA-12402 + U UUUGCAAAACUGGCGGGG 19 13045

BCLllA-10208 + AUUUUGCAAAACUGGCGGGG 20 13046

BCLllA-12403 + UAUUUUGCAAAACUGGCGGGG 21 13047

BCLllA-12404 + UUAUUUUGCAAAACUGGCGGGG 22 13048

BCLllA-12405 + AUUAUUUUGCAAAACUGGCGGGG 23 13049

BCLllA-12406 + CAUUAUUUUGCAAAACUGGCGGGG 24 13050

BCLllA-12407 + CGGGCGAGGGGAGGUGGG 18 13051

BCLllA-12408 + GCGGGCGAGGGGAGGUGGG 19 13052

BCLllA-10213 + AGCGGGCGAGGGGAGGUGGG 20 13053

BCLllA-12409 + CAGCGGGCGAGGGGAGGUGGG 21 13054

BCLllA-12410 + GCAGCGGGCGAGGGGAGGUGGG 22 13055

BCLllA-12411 + CGCAGCGGGCGAGGGGAGGUGGG 23 13056

BCLllA-12412 + CCGCAGCGGGCGAGGGGAGGUGGG 24 13057

BCLllA-12413 + AUUAUUUUGCAAAACUGG 18 13058

BCLllA-12414 + CAUUAUUUUGCAAAACUGG 19 13059

BCLllA-10215 + UCAUUAUUUUGCAAAACUGG 20 13060

BCLllA-12415 + U UCAUUAUUUUGCAAAACUGG 21 13061

BCLllA-12416 + GUUCAUUAUUUUGCAAAACUGG 22 13062

BCLllA-12417 + UGUUCAUUAUUUUGCAAAACUGG 23 13063

BCLllA-12418 + U UGUUCAUUAUUUUGCAAAACUGG 24 13064

BCLllA-12419 + ACAAACACCCACCUCUGG 18 13065

BCLllA-12420 + GACAAACACCCACCUCUGG 19 13066

BCLllA-12421 + GGACAAACACCCACCUCUGG 20 13067

BCLllA-12422 + GGGACAAACACCCACCUCUGG 21 13068

BCLllA-12423 + CGGGACAAACACCCACCUCUGG 22 13069

BCLllA-12424 + GCGGGACAAACACCCACCUCUGG 23 13070

BCLllA-12425 + AGCGGGACAAACACCCACCUCUGG 24 13071

BCLllA-12426 + GCGGGCGAGGGGAGGUGG 18 13072

BCLllA-12427 + AGCGGGCGAGGGGAGGUGG 19 13073

BCLllA-12428 + CAGCGGGCGAGGGGAGGUGG 20 13074

BCLllA-12429 + GCAGCGGGCGAGGGGAGGUGG 21 13075

BCLllA-12430 + CGCAGCGGGCGAGGGGAGGUGG 22 13076

BCLllA-12431 + CCGCAGCGGGCGAGGGGAGGUGG 23 13077

BCLllA-12432 + UCCGCAGCGGGCGAGGGGAGGUGG 24 13078

BCLllA-12433 + CAUUAUUUUGCAAAACUG 18 13079

BCLllA-12434 + UCAUUAUUUUGCAAAACUG 19 13080

BCLllA-12435 + U UCAUUAUUUUGCAAAACUG 20 13081

BCLllA-12436 + GUUCAUUAUUUUGCAAAACUG 21 13082 BCLllA-12437 + UGUUCAUUAUUUUGCAAAACUG 22 13083

BCLllA-12438 + U UGUUCAUUAUUUUGCAAAACUG 23 13084

BCLllA-12439 + AUUGUUCAUUAUUU UGCAAAACUG 24 13085

BCLllA-12440 + GGCUGCAGCCCCGGGCUG 18 13086

BCLllA-12441 + AGGCUGCAGCCCCGGGCUG 19 13087

BCLllA-10226 + GAGGCUGCAGCCCCGGGCUG 20 13088

BCLllA-12442 + GGAGGCUGCAGCCCCGGGCUG 21 13089

BCLllA-12443 + GGGAGGCUGCAGCCCCGGGCUG 22 13090

BCLllA-12444 + CGGGAGGCUGCAGCCCCGGGCUG 23 13091

BCLllA-12445 + CCGGGAGGCUGCAGCCCCGGGCUG 24 13092

BCLllA-12446 + GCCACU UUCUCACUAUUG 18 13093

BCLllA-12447 + UGCCACUUUCUCACUAU UG 19 13094

BCLllA-10230 + GUGCCACUUUCUCACUAUUG 20 13095

BCLllA-12448 + AGUGCCACUU UCUCACUAUUG 21 13096

BCLllA-12449 + CAGUGCCACUUUCUCACUAUUG 22 13097

BCLllA-12450 + ACAGUGCCACUUUCUCACUAUUG 23 13098

BCLllA-12451 + CACAGUGCCACUUUCUCACUAUUG 24 13099

BCLllA-12452 + GAAUCCAGCCUAAGUUUG 18 13100

BCLllA-12453 + GGAAUCCAGCCUAAGU UUG 19 13101

BCLllA-12454 + CGGAAUCCAGCCUAAGU UUG 20 13102

BCLllA-12455 + GCGGAAUCCAGCCUAAGUUUG 21 13103

BCLllA-12456 + CGCGGAAUCCAGCCUAAGUUUG 22 13104

BCLllA-12457 + ACGCGGAAUCCAGCCUAAGUUUG 23 13105

BCLllA-12458 + AACGCGGAAUCCAGCCUAAGUUUG 24 13106

BCLllA-12459 + CUCCCGACUCCGCGGACU 18 13107

BCLllA-12460 + UCUCCCGACUCCGCGGACU 19 13108

BCLllA-12461 + CUCUCCCGACUCCGCGGACU 20 13109

BCLllA-12462 + CCUCUCCCGACUCCGCGGACU 21 13110

BCLllA-12463 + CCCUCUCCCGACUCCGCGGACU 22 13111

BCLllA-12464 + CCCCUCUCCCGACUCCGCGGACU 23 13112

BCLllA-12465 + GCCCCUCUCCCGACUCCGCGGACU 24 13113

BCLllA-12466 + CGAGCCCGCGGCUGCGCU 18 13114

BCLllA-12467 + CCGAGCCCGCGGCUGCGCU 19 13115

BCLllA-10239 + CCCGAGCCCGCGGCUGCGCU 20 13116

BCLllA-12468 + CCCCGAGCCCGCGGCUGCGCU 21 13117

BCLllA-12469 + GCCCCGAGCCCGCGGCUGCGCU 22 13118

BCLllA-12470 + AGCCCCGAGCCCGCGGCUGCGCU 23 13119

BCLllA-12471 + AAGCCCCGAGCCCGCGGCUGCGCU 24 13120

BCLllA-12472 + AGGCUGCAGCCCCGGGCU 18 13121

BCLllA-12473 + GAGGCUGCAGCCCCGGGCU 19 13122

BCLllA-10240 + GGAGGCUGCAGCCCCGGGCU 20 13123

BCLllA-12474 + GGGAGGCUGCAGCCCCGGGCU 21 13124 BCLllA-12475 + CGGGAGGCUGCAGCCCCGGGCU 22 13125

BCLllA-12476 + CCGGGAGGCUGCAGCCCCGGGCU 23 13126

BCLllA-12477 + ACCGGGAGGCUGCAGCCCCGGGCU 24 13127

BCLllA-12478 + GCGGAAUCCAGCCUAAGU 18 13128

BCLllA-12479 + CGCGGAAUCCAGCCUAAGU 19 13129

BCLllA-12480 + ACGCGGAAUCCAGCCUAAGU 20 13130

BCLllA-12481 + AACGCGGAAUCCAGCCUAAGU 21 13131

BCLllA-12482 + CAACGCGGAAUCCAGCCUAAGU 22 13132

BCLllA-12483 + GCAACGCGGAAUCCAGCCUAAGU 23 13133

BCLllA-12484 + GGCAACGCGGAAUCCAGCCUAAGU 24 13134

BCLllA-12485 + CAUUUUCU UACGGUGAGU 18 13135

BCLllA-12486 + CCAUUUUCUUACGGUGAGU 19 13136

BCLllA-10244 + CCCAUUUUCUUACGGUGAGU 20 13137

BCLllA-12487 + CCCCAUU UUCUUACGGUGAGU 21 13138

BCLllA-12488 + CCCCCAUUUUCUUACGGUGAGU 22 13139

BCLllA-12489 + CCCCCCAUUUUCUUACGGUGAGU 23 13140

BCLllA-12490 + CCCCCCCAUUUUCUUACGGUGAGU 24 13141

BCLllA-12491 + CGCGCUCGCUCCCCGCGU 18 13142

BCLllA-12492 + CCGCGCUCGCUCCCCGCGU 19 13143

BCLllA-12493 + GCCGCGCUCGCUCCCCGCGU 20 13144

BCLllA-12494 + CGCCGCGCUCGCUCCCCGCGU 21 13145

BCLllA-12495 + CCGCCGCGCUCGCUCCCCGCGU 22 13146

BCLllA-12496 + GCCGCCGCGCUCGCUCCCCGCGU 23 13147

BCLllA-12497 + CGCCGCCGCGCUCGCUCCCCGCGU 24 13148

BCLllA-12498 + CAGCGGGCGAGGGGAGGU 18 13149

BCLllA-12499 + GCAGCGGGCGAGGGGAGGU 19 13150

BCLllA-10247 + CGCAGCGGGCGAGGGGAGGU 20 13151

BCLllA-12500 + CCGCAGCGGGCGAGGGGAGGU 21 13152

BCLllA-12501 + UCCGCAGCGGGCGAGGGGAGGU 22 13153

BCLllA-12502 + CUCCGCAGCGGGCGAGGGGAGGU 23 13154

BCLllA-12503 + GCUCCGCAGCGGGCGAGGGGAGGU 24 13155

BCLllA-12504 + GUUUGGAGGGCUGCGGGU 18 13156

BCLllA-12505 + AGUUUGGAGGGCUGCGGGU 19 13157

BCLllA-12506 + AAGUUUGGAGGGCUGCGGGU 20 13158

BCLllA-12507 + UAAGUUUGGAGGGCUGCGGGU 21 13159

BCLllA-12508 + CUAAGUUUGGAGGGCUGCGGGU 22 13160

BCLllA-12509 + CCUAAGUUUGGAGGGCUGCGGGU 23 13161

BCLllA-12510 + GCCUAAGUUUGGAGGGCUGCGGGU 24 13162

BCLllA-12511 + UGCCACUUUCUCACUAU U 18 13163

BCLllA-12512 + GUGCCACU UUCUCACUAUU 19 13164

BCLllA-12513 + AGUGCCACUUUCUCACUAUU 20 13165

BCLllA-12514 + CAGUGCCACUUUCUCACUAUU 21 13166 BCLllA-12515 + ACAGUGCCACUUUCUCACUAUU 22 13167

BCLllA-12516 + CACAGUGCCACUUUCUCACUAUU 23 13168

BCLllA-12517 + CCACAGUGCCACUUUCUCACUAUU 24 13169

BCLllA-12518 + GAAAAAUCACCCGAAGU U 18 13170

BCLllA-12519 + AG AAAAAU CACCCG AAG U U 19 13171

BCLllA-12520 + AAGAAAAAUCACCCGAAGUU 20 13172

BCLllA-12521 + AAAG AAAAAU CACCCG AAG U U 21 13173

BCLllA-12522 + CAAAG AAAAAU CACCCG AAG UU 22 13174

BCLllA-12523 + G CAAAG AAAAAU CACCCG AAG UU 23 13175

BCLllA-12524 + AGCAAAGAAAAAUCACCCGAAGUU 24 13176

BCLllA-12525 + CGGAAUCCAGCCUAAGUU 18 13177

BCLllA-12526 + GCGGAAUCCAGCCUAAGUU 19 13178

BCLllA-10257 + CGCGGAAUCCAGCCUAAGUU 20 13179

BCLllA-12527 + ACGCGGAAUCCAGCCUAAGUU 21 13180

BCLllA-12528 + AACGCGGAAUCCAGCCUAAGUU 22 13181

BCLllA-12529 + CAACGCGGAAUCCAGCCUAAGUU 23 13182

BCLllA-12530 + GCAACGCGGAAUCCAGCCUAAGUU 24 13183

BCLllA-12531 + GAAUCAUUGCAUUCCUUU 18 13184

BCLllA-12532 + GGAAUCAUUGCAUUCCU UU 19 13185

BCLllA-12533 + UGGAAUCAUUGCAUUCCUUU 20 13186

BCLllA-12534 + GUGGAAUCAUUGCAUUCCUUU 21 13187

BCLllA-12535 + AGUGGAAUCAUUGCAU UCCUUU 22 13188

BCLllA-12536 + GAGUGGAAUCAUUGCAUUCCUUU 23 13189

BCLllA-12537 + GGAGUGGAAUCAUUGCAUUCCUUU 24 13190

BCLllA-12538 - CCACUCACCGUAAGAAAA 18 13191

BCLllA-12539 - CCCACU CACCG U AAG AAAA 19 13192

BCLllA-10024 - UCCCACUCACCGUAAGAAAA 20 13193

BCLllA-12540 - U U CCCACU CACCG U AAG AAAA 21 13194

BCLllA-12541 - CU U CCCACU CACCG U AAG AAAA 22 13195

BCLllA-12542 - GCU U CCCACU CACCG U AAG AAAA 23 13196

BCLllA-12543 - UGCUUCCCACUCACCGUAAGAAAA 24 13197

BCLllA-12544 - CCCACU CACCG U AAG AAA 18 13198

BCLllA-12545 - U CCCACU CACCG U AAG AAA 19 13199

BCLllA-12546 - U UCCCACUCACCGUAAGAAA 20 13200

BCLllA-12547 - CUUCCCACUCACCGUAAGAAA 21 13201

BCLllA-12548 - GCUUCCCACUCACCGUAAGAAA 22 13202

BCLllA-12549 - UGCU UCCCACUCACCGUAAGAAA 23 13203

BCLllA-12550 - U UGCUUCCCACUCACCGUAAGAAA 24 13204

BCLllA-12551 - UGGGAGCUGGUGGGGAAA 18 13205

BCLllA-12552 - GUGGGAGCUGGUGGGGAAA 19 13206

BCLllA-10028 - GGUGGGAGCUGGUGGGGAAA 20 13207

BCLllA-12553 - GGGUGGGAGCUGGUGGGGAAA 21 13208 BCLllA-12554 - GGGGUGGGAGCUGGUGGGGAAA 22 13209

BCLllA-12555 - GGGGGUGGGAGCUGGUGGGGAAA 23 13210

BCLllA-12556 - UGGGGGUGGGAGCUGGUGGGGAAA 24 13211

BCLllA-12557 - AACGAUUCCCGGGGAGAA 18 13212

BCLllA-12558 - AAACGAUUCCCGGGGAGAA 19 13213

BCLllA-12559 - AAAACGAUUCCCGGGGAGAA 20 13214

BCLllA-12560 - AAAAACGAUUCCCGGGGAGAA 21 13215

BCLllA-12561 - AAAAAACGAUUCCCGGGGAGAA 22 13216

BCLllA-12562 - UAAAAAACGAUUCCCGGGGAGAA 23 13217

BCLllA-12563 - CUAAAAAACGAUUCCCGGGGAGAA 24 13218

BCLllA-12564 - UUUAUUUCUCUUUUCGAA 18 13219

BCLllA-12565 - CUUUAUUUCUCUUUUCGAA 19 13220

BCLllA-12566 - GCUUUAUUUCUCUUUUCGAA 20 13221

BCLllA-12567 - CGCUUUAUUUCUCUUUUCGAA 21 13222

BCLllA-12568 - CCGCUUUAUUUCUCUUUUCGAA 22 13223

BCLllA-12569 - GCCGCUUUAUUUCUCUUUUCGAA 23 13224

BCLllA-12570 - CGCCGCUUUAUUUCUCUUUUCGAA 24 13225

BCLllA-12571 - GUGGGAGCUGGUGGGGAA 18 13226

BCLllA-12572 - GGUGGGAGCUGGUGGGGAA 19 13227

BCLllA-10032 - GGGUGGGAGCUGGUGGGGAA 20 13228

BCLllA-12573 - GGGGUGGGAGCUGGUGGGGAA 21 13229

BCLllA-12574 - GGGGGUGGGAGCUGGUGGGGAA 22 13230

BCLllA-12575 - UGGGGGUGGGAGCUGGUGGGGAA 23 13231

BCLllA-12576 - CUGGGGGUGGGAGCUGGUGGGGAA 24 13232

BCLllA-12577 - GAAAGUGGCACUGUGGAA 18 13233

BCLllA-12578 - AGAAAGUGGCACUGUGGAA 19 13234

BCLllA-10033 - GAGAAAGUGGCACUGUGGAA 20 13235

BCLllA-12579 - UGAGAAAGUGGCACUGUGGAA 21 13236

BCLllA-12580 - GUGAGAAAGUGGCACUGUGGAA 22 13237

BCLllA-12581 - AGUGAGAAAGUGGCACUGUGGAA 23 13238

BCLllA-12582 - UAGUGAGAAAGUGGCACUGUGGAA 24 13239

BCLllA-12583 - CUCACGGUCAAGUGUGCA 18 13240

BCLllA-12584 - GCUCACGGUCAAGUGUGCA 19 13241

BCLllA-12585 - CGCUCACGGUCAAGUGUGCA 20 13242

BCLllA-12586 - GCGCUCACGGUCAAGUGUGCA 21 13243

BCLllA-12587 - CGCGCUCACGGUCAAGUGUGCA 22 13244

BCLllA-12588 - GCGCGCUCACGGUCAAGUGUGCA 23 13245

BCLllA-12589 - AGCGCGCUCACGGUCAAGUGUGCA 24 13246

BCLllA-12590 - GGAGAGGGGCCGCGGCGA 18 13247

BCLllA-12591 - GGGAGAGGGGCCGCGGCGA 19 13248

BCLllA-10043 - CGGGAGAGGGGCCGCGGCGA 20 13249

BCLllA-12592 - UCGGGAGAGGGGCCGCGGCGA 21 13250 BCLllA-12593 - GUCGGGAGAGGGGCCGCGGCGA 22 13251

BCLllA-12594 - AGUCGGGAGAGGGGCCGCGGCGA 23 13252

BCLllA-12595 - GAGUCGGGAGAGGGGCCGCGGCGA 24 13253

BCLllA-12596 - CCGUGGGACCGGGAAGGA 18 13254

BCLllA-12597 - GCCGUGGGACCGGGAAGGA 19 13255

BCLllA-10045 - AGCCGUGGGACCGGGAAGGA 20 13256

BCLllA-12598 - GAGCCGUGGGACCGGGAAGGA 21 13257

BCLllA-12599 - AGAGCCGUGGGACCGGGAAGGA 22 13258

BCLllA-12600 - GAGAGCCGUGGGACCGGGAAGGA 23 13259

BCLllA-12601 - GGAGAGCCGUGGGACCGGGAAGGA 24 13260

BCLllA-12602 - GAGUCCGCGGAGUCGGGA 18 13261

BCLllA-12603 - UGAGUCCGCGGAGUCGGGA 19 13262

BCLllA-12604 - CUGAGUCCGCGGAGUCGGGA 20 13263

BCLllA-12605 - CCUGAGUCCGCGGAGUCGGGA 21 13264

BCLllA-12606 - UCCUGAGUCCGCGGAGUCGGGA 22 13265

BCLllA-12607 - CUCCUGAGUCCGCGGAGUCGGGA 23 13266

BCLllA-12608 - GCUCCUGAGUCCGCGGAGUCGGGA 24 13267

BCLllA-12609 - GGCGUCCACACGCGGGGA 18 13268

BCLllA-12610 - UGGCGUCCACACGCGGGGA 19 13269

BCLllA-12611 - CUGGCGUCCACACGCGGGGA 20 13270

BCLllA-12612 - CCUGGCGUCCACACGCGGGGA 21 13271

BCLllA-12613 - CCCUGGCGUCCACACGCGGGGA 22 13272

BCLllA-12614 - CCCCUGGCGUCCACACGCGGGGA 23 13273

BCLllA-12615 - GCCCCUGGCGUCCACACGCGGGGA 24 13274

BCLllA-12616 - GCGCGGCGGCGGCGGGGA 18 13275

BCLllA-12617 - AGCGCGGCGGCGGCGGGGA 19 13276

BCLllA-10051 - GAGCGCGGCGGCGGCGGGGA 20 13277

BCLllA-12618 - CGAGCGCGGCGGCGGCGGGGA 21 13278

BCLllA-12619 - GCGAGCGCGGCGGCGGCGGGGA 22 13279

BCLllA-12620 - AGCGAGCGCGGCGGCGGCGGGGA 23 13280

BCLllA-12621 - GAGCGAGCGCGGCGGCGGCGGGGA 24 13281

BCLllA-12622 - GGUGGGAGCUGGUGGGGA 18 13282

BCLllA-12623 - GGGUGGGAGCUGGUGGGGA 19 13283

BCLllA-12624 - GGGGUGGGAGCUGGUGGGGA 20 13284

BCLllA-12625 - GGGGGUGGGAGCUGGUGGGGA 21 13285

BCLllA-12626 - UGGGGGUGGGAGCUGGUGGGGA 22 13286

BCLllA-12627 - CUGGGGGUGGGAGCUGGUGGGGA 23 13287

BCLllA-12628 - CCUGGGGGUGGGAGCUGGUGGGGA 24 13288

BCLllA-12629 - ACGGGGAGAGCCGUGGGA 18 13289

BCLllA-12630 - GACGGGGAGAGCCGUGGGA 19 13290

BCLllA-12631 - CGACGGGGAGAGCCGUGGGA 20 13291

BCLllA-12632 - GCGACGGGGAGAGCCGUGGGA 21 13292 BCLllA-12633 - GGCGACGGGGAGAGCCGUGGGA 22 13293

BCLllA-12634 - CGGCGACGGGGAGAGCCGUGGGA 23 13294

BCLllA-12635 - GCGGCGACGGGGAGAGCCGUGGGA 24 13295

BCLllA-12636 - AGAAAGUGGCACUGUGGA 18 13296

BCLllA-12637 - GAGAAAGUGGCACUGUGGA 19 13297

BCLllA-12638 - UGAGAAAGUGGCACUGUGGA 20 13298

BCLllA-12639 - GUGAGAAAGUGGCACUGUGGA 21 13299

BCLllA-12640 - AGUGAGAAAGUGGCACUGUGGA 22 13300

BCLllA-12641 - UAGUGAGAAAGUGGCACUGUGGA 23 13301

BCLllA-12642 - AUAGUGAGAAAGUGGCACUGUGGA 24 13302

BCLllA-12643 - CGCCAGUUUUG C A A A A U A 18 13303

BCLllA-12644 - CCGCCAGUUUUGCAAAAUA 19 13304

BCLllA-12645 - CCCGCCAGUUUUGCAAAAUA 20 13305

BCLllA-12646 - CCCCGCCAGUUUUGCAAAAUA 21 13306

BCLllA-12647 - GCCCCGCCAGUUUUGCAAAAUA 22 13307

BCLllA-12648 - CGCCCCGCCAGUUUUGCAAAAUA 23 13308

BCLllA-12649 - CCGCCCCGCCAGUUUUGCAAAAUA 24 13309

BCLllA-12650 - GUAGUCAUCCCCACAAUA 18 13310

BCLllA-12651 - AGUAGUCAUCCCCACAAUA 19 13311

BCLllA-12652 - AAGUAGUCAUCCCCACAAUA 20 13312

BCLllA-12653 - AAAGUAGUCAUCCCCACAAUA 21 13313

BCLllA-12654 - GAAAGUAGUCAUCCCCACAAUA 22 13314

BCLllA-12655 - GGAAAGUAGUCAUCCCCACAAUA 23 13315

BCLllA-12656 - AGGAAAGUAGUCAUCCCCACAAUA 24 13316

BCLllA-12657 - GGGAAGUGGGUGUGCGUA 18 13317

BCLllA-12658 - GGGGAAGUGGGUGUGCGUA 19 13318

BCLllA-10055 - AGGGGAAGUGGGUGUGCGUA 20 13319

BCLllA-12659 - GAGGGGAAGUGGGUGUGCGUA 21 13320

BCLllA-12660 - GGAGGGGAAGUGGGUGUGCGUA 22 13321

BCLllA-12661 - GGGAGGGGAAGUGGGUGUGCGUA 23 13322

BCLllA-12662 - GGGGAGGGGAAGUGGGUGUGCGUA 24 13323

BCLllA-12663 - UAAGAAAAUGGGGGGGUA 18 13324

BCLllA-12664 - GUAAGAAAAUGGGGGGGUA 19 13325

BCLllA-10056 - CGUAAGAAAAUGGGGGGGUA 20 13326

BCLllA-12665 - CCGUAAGAAAAUGGGGGGGUA 21 13327

BCLllA-12666 - ACCGUAAGAAAAUGGGGGGGUA 22 13328

BCLllA-12667 - CACCGUAAGAAAAUGGGGGGGUA 23 13329

BCLllA-12668 - UCACCGUAAGAAAAUGGGGGGGUA 24 13330

BCLllA-12669 - AACAACUCACAUGCAAAC 18 13331

BCLllA-12670 - G A ACAAC U CAC AU G CAAAC 19 13332

BCLllA-12671 - CGAACAACUCACAUGCAAAC 20 13333

BCLllA-12672 - GCGAACAACUCACAUGCAAAC 21 13334 BCLllA-12673 - U G CG AACAAC U CAC AU G CAAAC 22 13335

BCLllA-12674 - UUGCGAACAACUCACAUGCAAAC 23 13336

BCLllA-12675 - GUUGCGAACAACUCACAUGCAAAC 24 13337

BCLllA-12676 - CCGCUGCGGAGCUGUAAC 18 13338

BCLllA-12677 - CCCGCUGCGGAGCUGUAAC 19 13339

BCLllA-12678 - GCCCGCUGCGGAGCUGUAAC 20 13340

BCLllA-12679 - CGCCCGCUGCGGAGCUGUAAC 21 13341

BCLllA-12680 - UCGCCCGCUGCGGAGCUGUAAC 22 13342

BCLllA-12681 - CUCGCCCGCUGCGGAGCUGUAAC 23 13343

BCLllA-12682 - CCUCGCCCGCUGCGGAGCUGUAAC 24 13344

BCLllA-12683 - GGCCCCUGGCGUCCACAC 18 13345

BCLllA-12684 - CGGCCCCUGGCGUCCACAC 19 13346

BCLllA-12685 - UCGGCCCCUGGCGUCCACAC 20 13347

BCLllA-12686 - UUCGGCCCCUGGCGUCCACAC 21 13348

BCLllA-12687 - CUUCGGCCCCUGGCGUCCACAC 22 13349

BCLllA-12688 - ACUUCGGCCCCUGGCGUCCACAC 23 13350

BCLllA-12689 - UACUUCGGCCCCUGGCGUCCACAC 24 13351

BCLllA-12690 - GCGCGGGCUCCUGGAGAC 18 13352

BCLllA-12691 - CGCGCGGGCUCCUGGAGAC 19 13353

BCLllA-12692 - CCGCGCGGGCUCCUGGAGAC 20 13354

BCLllA-12693 - GCCGCGCGGGCUCCUGGAGAC 21 13355

BCLllA-12694 - GGCCGCGCGGGCUCCUGGAGAC 22 13356

BCLllA-12695 - AGGCCGCGCGGGCUCCUGGAGAC 23 13357

BCLllA-12696 - CAGGCCGCGCGGGCUCCUGGAGAC 24 13358

BCLllA-12697 - GAGAGGGGCCGCGGCGAC 18 13359

BCLllA-12698 - GGAGAGGGGCCGCGGCGAC 19 13360

BCLllA-10061 - GGGAGAGGGGCCGCGGCGAC 20 13361

BCLllA-12699 - CGGGAGAGGGGCCGCGGCGAC 21 13362

BCLllA-12700 - UCGGGAGAGGGGCCGCGGCGAC 22 13363

BCLllA-12701 - GUCGGGAGAGGGGCCGCGGCGAC 23 13364

BCLllA-12702 - AGUCGGGAGAGGGGCCGCGGCGAC 24 13365

BCLllA-12703 - CGUGGGACCGGGAAGGAC 18 13366

BCLllA-12704 - CCGUGGGACCGGGAAGGAC 19 13367

BCLllA-10062 - GCCGUGGGACCGGGAAGGAC 20 13368

BCLllA-12705 - AGCCGUGGGACCGGGAAGGAC 21 13369

BCLllA-12706 - GAGCCGUGGGACCGGGAAGGAC 22 13370

BCLllA-12707 - AGAGCCGUGGGACCGGGAAGGAC 23 13371

BCLllA-12708 - GAGAGCCGUGGGACCGGGAAGGAC 24 13372

BCLllA-12709 - CGGGGAGAGCCGUGGGAC 18 13373

BCLllA-12710 - ACGGGGAGAGCCGUGGGAC 19 13374

BCLllA-10065 - GACGGGGAGAGCCGUGGGAC 20 13375

BCLllA-12711 - CGACGGGGAGAGCCGUGGGAC 21 13376 BCLllA-12712 - GCGACGGGGAGAGCCGUGGGAC 22 13377

BCLllA-12713 - GGCGACGGGGAGAGCCGUGGGAC 23 13378

BCLllA-12714 - CGGCGACGGGGAGAGCCGUGGGAC 24 13379

BCLllA-12715 - ACAACUCACAUGCAAACC 18 13380

BCLllA-12716 - AACAACUCACAUGCAAACC 19 13381

BCLllA-10066 - GAACAACUCACAUGCAAACC 20 13382

BCLllA-12717 - CGAACAACUCACAUGCAAACC 21 13383

BCLllA-12718 - GCGAACAACUCACAUGCAAACC 22 13384

BCLllA-12719 - UGCGAACAACUCACAUGCAAACC 23 13385

BCLllA-12720 - UUGCGAACAACUCACAUGCAAACC 24 13386

BCLllA-12721 - GGGGAGAGCCGUGGGACC 18 13387

BCLllA-12722 - CGGGGAGAGCCGUGGGACC 19 13388

BCLllA-10070 - ACGGGGAGAGCCGUGGGACC 20 13389

BCLllA-12723 - GACGGGGAGAGCCGUGGGACC 21 13390

BCLllA-12724 - CGACGGGGAGAGCCGUGGGACC 22 13391

BCLllA-12725 - GCGACGGGGAGAGCCGUGGGACC 23 13392

BCLllA-12726 - GGCGACGGGGAGAGCCGUGGGACC 24 13393

BCLllA-12727 - UCGGCCUUGGGGGCGCCC 18 13394

BCLllA-12728 - CUCGGCCUUGGGGGCGCCC 19 13395

BCLllA-12729 - GCUCGGCCUUGGGGGCGCCC 20 13396

BCLllA-12730 - GGCUCGGCCUUGGGGGCGCCC 21 13397

BCLllA-12731 - UGGCUCGGCCUUGGGGGCGCCC 22 13398

BCLllA-12732 - CUGGCUCGGCCUUGGGGGCGCCC 23 13399

BCLllA-12733 - CCUGGCUCGGCCUUGGGGGCGCCC 24 13400

BCLllA-12734 - GUCUAAAAAACGAUUCCC 18 13401

BCLllA-12735 - AGUCUAAAAAACGAUUCCC 19 13402

BCLllA-10082 - AAGUCUAAAAAACGAUUCCC 20 13403

BCLllA-12736 - CAAGUCUAAAAAACGAUUCCC 21 13404

BCLllA-12737 - ACAAGUCUAAAAAACGAUUCCC 22 13405

BCLllA-12738 - UACAAGUCUAAAAAACGAUUCCC 23 13406

BCLllA-12739 - GUACAAGUCUAAAAAACGAUUCCC 24 13407

BCLllA-12740 - GCCCGCGCUUCCCCAGCC 18 13408

BCLllA-12741 - CGCCCGCGCUUCCCCAGCC 19 13409

BCLllA-10084 - CCGCCCGCGCUUCCCCAGCC 20 13410

BCLllA-12742 - UCCGCCCGCGCUUCCCCAGCC 21 13411

BCLllA-12743 - CUCCGCCCGCGCUUCCCCAGCC 22 13412

BCLllA-12744 - CCUCCGCCCGCGCUUCCCCAGCC 23 13413

BCLllA-12745 - CCCUCCGCCCGCGCUUCCCCAGCC 24 13414

BCLllA-12746 - AGUUUCCCGAGCGCAGCC 18 13415

BCLllA-12747 - A AG UUUCCCGAG CG C AG CC 19 13416

BCLllA-12748 - AAAGUUUCCCGAGCGCAGCC 20 13417

BCLllA-12749 - CAAAGUUUCCCGAGCGCAGCC 21 13418 BCLllA-12750 - GCAAAGUUUCCCGAGCGCAGCC 22 13419

BCLllA-12751 - GGCAAAGUUUCCCGAGCGCAGCC 23 13420

BCLllA-12752 - GGGCAAAGUUUCCCGAGCGCAGCC 24 13421

BCLllA-12753 - GCGGCGACGGGGAGAGCC 18 13422

BCLllA-12754 - CGCGGCGACGGGGAGAGCC 19 13423

BCLllA-12755 - CCGCGGCGACGGGGAGAGCC 20 13424

BCLllA-12756 - GCCGCGGCGACGGGGAGAGCC 21 13425

BCLllA-12757 - GGCCGCGGCGACGGGGAGAGCC 22 13426

BCLllA-12758 - GGGCCGCGGCGACGGGGAGAGCC 23 13427

BCLllA-12759 - GGGGCCGCGGCGACGGGGAGAGCC 24 13428

BCLllA-12760 - CCGGUCCCUGGCUCGGCC 18 13429

BCLllA-12761 - CCCGGUCCCUGGCUCGGCC 19 13430

BCLllA-12762 - UCCCGGUCCCUGGCUCGGCC 20 13431

BCLllA-12763 - CCAGGCCGCGCGGGCUCC 18 13432

BCLllA-12764 - UCCAGGCCGCGCGGGCUCC 19 13433

BCLllA-10091 - UUCCAGGCCGCGCGGGCUCC 20 13434

BCLllA-12765 - UUUCCAGGCCGCGCGGGCUCC 21 13435

BCLllA-12766 - CUUUCCAGGCCGCGCGGGCUCC 22 13436

BCLllA-12767 - UCUUUCCAGGCCGCGCGGGCUCC 23 13437

BCLllA-12768 - CUCUUUCCAGGCCGCGCGGGCUCC 24 13438

BCLllA-12769 - UUCUUUGCUGUCCUCUCC 18 13439

BCLllA-12770 - UUUCUUUGCUGUCCUCUCC 19 13440

BCLllA-12771 - UUUUCUUUGCUGUCCUCUCC 20 13441

BCLllA-12772 - UUUUUCUUUGCUGUCCUCUCC 21 13442

BCLllA-12773 - AUUUUUCUUUGCUGUCCUCUCC 22 13443

BCLllA-12774 - GAUUUUUCUUUGCUGUCCUCUCC 23 13444

BCLllA-12775 - UGAUUUUUCUUUGCUGUCCUCUCC 24 13445

BCLllA-12776 - CCCGGCGCUCCUGAGUCC 18 13446

BCLllA-12777 - CCCCGGCGCUCCUGAGUCC 19 13447

BCLllA-12778 - CCCCCGGCGCUCCUGAGUCC 20 13448

BCLllA-12779 - GCCCCCGGCGCUCCUGAGUCC 21 13449

BCLllA-12780 - GGCCCCCGGCGCUCCUGAGUCC 22 13450

BCLllA-12781 - GGGCCCCCGGCGCUCCUGAGUCC 23 13451

BCLllA-12782 - GGGGCCCCCGGCGCUCCUGAGUCC 24 13452

BCLllA-12783 - GUACGGAGGAGGGUGUCC 18 13453

BCLllA-12784 - CGUACGGAGGAGGGUGUCC 19 13454

BCLllA-10094 - GCGUACGGAGGAGGGUGUCC 20 13455

BCLllA-12785 - UGCGUACGGAGGAGGGUGUCC 21 13456

BCLllA-12786 - GUGCGUACGGAGGAGGGUGUCC 22 13457

BCLllA-12787 - UGUGCGUACGGAGGAGGGUGUCC 23 13458

BCLllA-12788 - GUGUGCGUACGGAGGAGGGUGUCC 24 13459

BCLllA-12789 - AGUCUAAAAAACGAUUCC 18 13460 BCLllA-12790 - AAGUCUAAAAAACGAUUCC 19 13461

BCLllA-10095 - CAAGUCUAAAAAACGAUUCC 20 13462

BCLllA-12791 - ACAAGUCUAAAAAACGAUUCC 21 13463

BCLllA-12792 - UACAAGUCUAAAAAACGAUUCC 22 13464

BCLllA-12793 - GU ACAAGUCUAAAAAACGAUUCC 23 13465

BCLllA-12794 - AGUACAAGUCUAAAAAACGAUUCC 24 13466

BCLllA-12795 - CGCCCGCGCUUCCCCAGC 18 13467

BCLllA-12796 - CCGCCCGCGCUUCCCCAGC 19 13468

BCLllA-12797 - UCCGCCCGCGCUUCCCCAGC 20 13469

BCLllA-12798 - CUCCGCCCGCGCUUCCCCAGC 21 13470

BCLllA-12799 - CCUCCGCCCGCGCUUCCCCAGC 22 13471

BCLllA-12800 - CCCUCCGCCCGCGCUUCCCCAGC 23 13472

BCLllA-12801 - UCCCUCCGCCCGCGCUUCCCCAGC 24 13473

BCLllA-12802 - CACGGUCAAGUGUGCAGC 18 13474

BCLllA-12803 - UCACGGUCAAGUGUGCAGC 19 13475

BCLllA-10100 - CUCACGGUCAAGUGUGCAGC 20 13476

BCLllA-12804 - GCUCACGGUCAAGUGUGCAGC 21 13477

BCLllA-12805 - CGCUCACGGUCAAGUGUGCAGC 22 13478

BCLllA-12806 - GCGCUCACGGUCAAGUGUGCAGC 23 13479

BCLllA-12807 - CGCGCUCACGGUCAAGUGUGCAGC 24 13480

BCLllA-12808 - CCCCUGGCGUCCACACGC 18 13481

BCLllA-12809 - GCCCCUGGCGUCCACACGC 19 13482

BCLllA-10103 - GGCCCCUGGCGUCCACACGC 20 13483

BCLllA-12810 - CGGCCCCUGGCGUCCACACGC 21 13484

BCLllA-12811 - UCGGCCCCUGGCGUCCACACGC 22 13485

BCLllA-12812 - UUCGGCCCCUGGCGUCCACACGC 23 13486

BCLllA-12813 - CUUCGGCCCCUGGCGUCCACACGC 24 13487

BCLllA-12814 - CCCCUCUUUCCAGGCCGC 18 13488

BCLllA-12815 - UCCCCUCUUUCCAGGCCGC 19 13489

BCLllA-12816 - GUCCCCUCUUUCCAGGCCGC 20 13490

BCLllA-12817 - GGUCCCCUCUUUCCAGGCCGC 21 13491

BCLllA-12818 - CGGUCCCCUCUUUCCAGGCCGC 22 13492

BCLllA-12819 - CCGGUCCCCUCUUUCCAGGCCGC 23 13493

BCLllA-12820 - CCCGGUCCCCUCUUUCCAGGCCGC 24 13494

BCLllA-12821 - GCCGCCUUUUGUUCCGGC 18 13495

BCLllA-12822 - UGCCGCCUUUUGUUCCGGC 19 13496

BCLllA-12823 - CUGCCGCCUUUUGUUCCGGC 20 13497

BCLllA-12824 - ACUGCCGCCUUUUGUUCCGGC 21 13498

BCLllA-12825 - CACUGCCGCCUUUUGUUCCGGC 22 13499

BCLllA-12826 - GCACUGCCGCCUUUUGUUCCGGC 23 13500

BCLllA-12827 - GGCACUGCCGCCUUUUGUUCCGGC 24 13501

BCLllA-12828 - AGCGAGCGCGGCGGCGGC 18 13502 BCLllA-12829 - GAGCGAGCGCGGCGGCGGC 19 13503

BCLllA-10114 - GGAGCGAGCGCGGCGGCGGC 20 13504

BCLllA-12830 - GGGAGCGAGCGCGGCGGCGGC 21 13505

BCLllA-12831 - GGGGAGCGAGCGCGGCGGCGGC 22 13506

BCLllA-12832 - CGGGGAGCGAGCGCGGCGGCGGC 23 13507

BCLllA-12833 - GCGGGGAGCGAGCGCGGCGGCGGC 24 13508

BCLllA-12834 - CCGAGCGCAGCCGCGGGC 18 13509

BCLllA-12835 - CCCGAGCGCAGCCGCGGGC 19 13510

BCLllA-12836 - UCCCGAGCGCAGCCGCGGGC 20 13511

BCLllA-12837 - UUCCCGAGCGCAGCCGCGGGC 21 13512

BCLllA-12838 - UUUCCCGAGCGCAGCCGCGGGC 22 13513

BCLllA-12839 - GUUUCCCGAGCGCAGCCGCGGGC 23 13514

BCLllA-12840 - AGUUUCCCGAGCGCAGCCGCGGGC 24 13515

BCLllA-12841 - UCCAGGCCGCGCGGGCUC 18 13516

BCLllA-12842 - UUCCAGGCCGCGCGGGCUC 19 13517

BCLllA-12843 - UUUCCAGGCCGCGCGGGCUC 20 13518

BCLllA-12844 - CUUUCCAGGCCGCGCGGGCUC 21 13519

BCLllA-12845 - UCUUUCCAGGCCGCGCGGGCUC 22 13520

BCLllA-12846 - CUCUUUCCAGGCCGCGCGGGCUC 23 13521

BCLllA-12847 - CCUCUUUCCAGGCCGCGCGGGCUC 24 13522

BCLllA-12848 - UCCUGAGUCCGCGGAGUC 18 13523

BCLllA-12849 - CUCCUGAGUCCGCGGAGUC 19 13524

BCLllA-10128 - GCUCCUGAGUCCGCGGAGUC 20 13525

BCLllA-12850 - CGCUCCUGAGUCCGCGGAGUC 21 13526

BCLllA-12851 - GCGCUCCUGAGUCCGCGGAGUC 22 13527

BCLllA-12852 - GGCGCUCCUGAGUCCGCGGAGUC 23 13528

BCLllA-12853 - CGGCGCUCCUGAGUCCGCGGAGUC 24 13529

BCLllA-12854 - CGUACGGAGGAGGGUGUC 18 13530

BCLllA-12855 - GCGUACGGAGGAGGGUGUC 19 13531

BCLllA-10130 - UGCGUACGGAGGAGGGUGUC 20 13532

BCLllA-12856 - GUGCGUACGGAGGAGGGUGUC 21 13533

BCLllA-12857 - UGUGCGUACGGAGGAGGGUGUC 22 13534

BCLllA-12858 - GUGUGCGUACGGAGGAGGGUGUC 23 13535

BCLllA-12859 - GGUGUGCGUACGGAGGAGGGUGUC 24 13536

BCLllA-12860 - AAGUCUAAAAAACGAUUC 18 13537

BCLllA-12861 - CAAGUCUAAAAAACGAUUC 19 13538

BCLllA-12862 - ACAAGUCUAAAAAACGAUUC 20 13539

BCLllA-12863 - UACAAGUCUAAAAAACGAUUC 21 13540

BCLllA-12864 - GUACAAGUCUAAAAAACGAUUC 22 13541

BCLllA-12865 - AG UACAAG U CU AAAAAACG AU U C 23 13542

BCLllA-12866 - GAGUACAAGUCUAAAAAACGAUUC 24 13543

BCLllA-12867 - CUCCUCGGGCAAAGUUUC 18 13544 BCLllA-12868 - UCUCCUCGGGCAAAGUUUC 19 13545

BCLllA-12869 - CUCUCCUCGGGCAAAGUUUC 20 13546

BCLllA-12870 - CCUCUCCUCGGGCAAAGUUUC 21 13547

BCLllA-12871 - UCCUCUCCUCGGGCAAAGUUUC 22 13548

BCLllA-12872 - GUCCUCUCCUCGGGCAAAGUUUC 23 13549

BCLllA-12873 - UGUCCUCUCCUCGGGCAAAGUUUC 24 13550

BCLllA-12874 - UCACGGUCAAGUGUGCAG 18 13551

BCLllA-12875 - CUCACGGUCAAGUGUGCAG 19 13552

BCLllA-10145 - GCUCACGGUCAAGUGUGCAG 20 13553

BCLllA-12876 - CGCUCACGGUCAAGUGUGCAG 21 13554

BCLllA-12877 - GCGCUCACGGUCAAGUGUGCAG 22 13555

BCLllA-12878 - CGCGCUCACGGUCAAGUGUGCAG 23 13556

BCLllA-12879 - GCGCGCUCACGGUCAAGUGUGCAG 24 13557

BCLllA-12880 - UUCCCGGGGAGAAAAGAG 18 13558

BCLllA-12881 - AUUCCCGGGGAGAAAAGAG 19 13559

BCLllA-12882 - GAUUCCCGGGGAGAAAAGAG 20 13560

BCLllA-12883 - CGAUUCCCGGGGAGAAAAGAG 21 13561

BCLllA-12884 - ACGAUUCCCGGGGAGAAAAGAG 22 13562

BCLllA-12885 - AACGAUUCCCGGGGAGAAAAGAG 23 13563

BCLllA-12886 - AAACGAUUCCCGGGGAGAAAAGAG 24 13564

BCLllA-12887 - GCUCCUGAGUCCGCGGAG 18 13565

BCLllA-12888 - CGCUCCUGAGUCCGCGGAG 19 13566

BCLllA-12889 - GCGCUCCUGAGUCCGCGGAG 20 13567

BCLllA-12890 - GGCGCUCCUGAGUCCGCGGAG 21 13568

BCLllA-12891 - CGGCGCUCCUGAGUCCGCGGAG 22 13569

BCLllA-12892 - CCGGCGCUCCUGAGUCCGCGGAG 23 13570

BCLllA-12893 - CCCGGCGCUCCUGAGUCCGCGGAG 24 13571

BCLllA-12894 - AGUCCGCGGAGUCGGGAG 18 13572

BCLllA-12895 - GAGUCCGCGGAGUCGGGAG 19 13573

BCLllA-10150 - UGAGUCCGCGGAGUCGGGAG 20 13574

BCLllA-12896 - CUGAGUCCGCGGAGUCGGGAG 21 13575

BCLllA-12897 - CCUGAGUCCGCGGAGUCGGGAG 22 13576

BCLllA-12898 - UCCUGAGUCCGCGGAGUCGGGAG 23 13577

BCLllA-12899 - CUCCUGAGUCCGCGGAGUCGGGAG 24 13578

BCLllA-12900 - CGCGGCGGCGGCGGGGAG 18 13579

BCLllA-12901 - GCGCGGCGGCGGCGGGGAG 19 13580

BCLllA-10152 - AGCGCGGCGGCGGCGGGGAG 20 13581

BCLllA-12902 - GAGCGCGGCGGCGGCGGGGAG 21 13582

BCLllA-12903 - CGAGCGCGGCGGCGGCGGGGAG 22 13583

BCLllA-12904 - GCGAGCGCGGCGGCGGCGGGGAG 23 13584

BCLllA-12905 - AGCGAGCGCGGCGGCGGCGGGGAG 24 13585

BCLllA-11434 - CGCGUGUGUGGGGGGGAG 18 13586 BCLllA-11435 - CCGCGUGUGUGGGGGGGAG 19 13587

BCLllA-11436 - UCCGCGUGUGUGGGGGGGAG 20 13588

BCLllA-11437 - GUCCGCGUGUGUGGGGGGGAG 21 13589

BCLllA-11438 - AGUCCGCGUGUGUGGGGGGGAG 22 13590

BCLllA-11439 - GAGUCCGCGUGUGUGGGGGGGAG 23 13591

BCLllA-11440 - AGAGUCCGCGUGUGUGGGGGGGAG 24 13592

BCLllA-12906 - GCCCCUGGCGUCCACACG 18 13593

BCLllA-12907 - GGCCCCUGGCGUCCACACG 19 13594

BCLllA-10156 - CGGCCCCUGGCGUCCACACG 20 13595

BCLllA-12908 - UCGGCCCCUGGCGUCCACACG 21 13596

BCLllA-12909 - UUCGGCCCCUGGCGUCCACACG 22 13597

BCLllA-12910 - CUUCGGCCCCUGGCGUCCACACG 23 13598

BCLllA-12911 - ACUUCGGCCCCUGGCGUCCACACG 24 13599

BCLllA-12912 - AGAGGGGCCGCGGCGACG 18 13600

BCLllA-12913 - GAGAGGGGCCGCGGCGACG 19 13601

BCLllA-10158 - GGAGAGGGGCCGCGGCGACG 20 13602

BCLllA-12914 - GGGAGAGGGGCCGCGGCGACG 21 13603

BCLllA-12915 - CGGGAGAGGGGCCGCGGCGACG 22 13604

BCLllA-12916 - UCGGGAGAGGGGCCGCGGCGACG 23 13605

BCLllA-12917 - GUCGGGAGAGGGGCCGCGGCGACG 24 13606

BCLllA-12918 - GAAGUGGGUGUGCGUACG 18 13607

BCLllA-12919 - GGAAGUGGGUGUGCGUACG 19 13608

BCLllA-12920 - GGGAAGUGGGUGUGCGUACG 20 13609

BCLllA-12921 - GGGGAAGUGGGUGUGCGUACG 21 13610

BCLllA-12922 - AGGGGAAGUGGGUGUGCGUACG 22 13611

BCLllA-12923 - GAGGGGAAGUGGGUGUGCGUACG 23 13612

BCLllA-12924 - GGAGGGGAAGUGGGUGUGCGUACG 24 13613

BCLllA-12925 - U CU AAAAAACG AU U CCCG 18 13614

BCLllA-12926 - GUCUAAAAAACGAUUCCCG 19 13615

BCLllA-10164 - AGUCUAAAAAACGAUUCCCG 20 13616

BCLllA-12927 - AAGUCUAAAAAACGAUUCCCG 21 13617

BCLllA-12928 - CAAGUCUAAAAAACGAUUCCCG 22 13618

BCLllA-12929 - ACAAGUCUAAAAAACGAUUCCCG 23 13619

BCLllA-12930 - UACAAGUCUAAAAAACGAUUCCCG 24 13620

BCLllA-12931 - CGGCGACGGGGAGAGCCG 18 13621

BCLllA-12932 - GCGGCGACGGGGAGAGCCG 19 13622

BCLllA-10166 - CGCGGCGACGGGGAGAGCCG 20 13623

BCLllA-12933 - CCGCGGCGACGGGGAGAGCCG 21 13624

BCLllA-12934 - GCCGCGGCGACGGGGAGAGCCG 22 13625

BCLllA-12935 - GGCCGCGGCGACGGGGAGAGCCG 23 13626

BCLllA-12936 - GGGCCGCGGCGACGGGGAGAGCCG 24 13627

BCLllA-12937 - CCCUGGCGUCCACACGCG 18 13628 BCLllA-12938 - CCCCUGGCGUCCACACGCG 19 13629

BCLllA-10175 - GCCCCUGGCGUCCACACGCG 20 13630

BCLllA-12939 - GGCCCCUGGCGUCCACACGCG 21 13631

BCLllA-12940 - CGGCCCCUGGCGUCCACACGCG 22 13632

BCLllA-12941 - UCGGCCCCUGGCGUCCACACGCG 23 13633

BCLllA-12942 - UUCGGCCCCUGGCGUCCACACGCG 24 13634

BCLllA-12943 - GGGAGAGGGGCCGCGGCG 18 13635

BCLllA-12944 - CGGGAGAGGGGCCGCGGCG 19 13636

BCLllA-12945 - UCGGGAGAGGGGCCGCGGCG 20 13637

BCLllA-12946 - GUCGGGAGAGGGGCCGCGGCG 21 13638

BCLllA-12947 - AGUCGGGAGAGGGGCCGCGGCG 22 13639

BCLllA-12948 - GAGUCGGGAGAGGGGCCGCGGCG 23 13640

BCLllA-12949 - GGAGUCGGGAGAGGGGCCGCGGCG 24 13641

BCLllA-12950 - GGAGCGAGCGCGGCGGCG 18 13642

BCLllA-12951 - GGGAGCGAGCGCGGCGGCG 19 13643

BCLllA-12952 - GGGGAGCGAGCGCGGCGGCG 20 13644

BCLllA-12953 - CGGGGAGCGAGCGCGGCGGCG 21 13645

BCLllA-12954 - GCGGGGAGCGAGCGCGGCGGCG 22 13646

BCLllA-12955 - CGCGGGGAGCGAGCGCGGCGGCG 23 13647

BCLllA-12956 - ACGCGGGGAGCGAGCGCGGCGGCG 24 13648

BCLllA-12957 - GCGAGCGCGGCGGCGGCG 18 13649

BCLllA-12958 - AGCGAGCGCGGCGGCGGCG 19 13650

BCLllA-10179 - GAGCGAGCGCGGCGGCGGCG 20 13651

BCLllA-12959 - GGAGCGAGCGCGGCGGCGGCG 21 13652

BCLllA-12960 - GGGAGCGAGCGCGGCGGCGGCG 22 13653

BCLllA-12961 - GGGGAGCGAGCGCGGCGGCGGCG 23 13654

BCLllA-12962 - CGGGGAGCGAGCGCGGCGGCGGCG 24 13655

BCLllA-12963 - GCCGUGGGACCGGGAAGG 18 13656

BCLllA-12964 - AGCCGUGGGACCGGGAAGG 19 13657

BCLllA-12965 - GAGCCGUGGGACCGGGAAGG 20 13658

BCLllA-12966 - AGAGCCGUGGGACCGGGAAGG 21 13659

BCLllA-12967 - GAGAGCCGUGGGACCGGGAAGG 22 13660

BCLllA-12968 - GGAGAGCCGUGGGACCGGGAAGG 23 13661

BCLllA-12969 - GGGAGAGCCGUGGGACCGGGAAGG 24 13662

BCLllA-12970 - AGAAAAUGGGGGGGUAGG 18 13663

BCLllA-12971 - AAGAAAAUGGGGGGGUAGG 19 13664

BCLllA-12972 - UAAGAAAAUGGGGGGGUAGG 20 13665

BCLllA-12973 - GUAAGAAAAUGGGGGGGUAGG 21 13666

BCLllA-12974 - CGUAAGAAAAUGGGGGGGUAGG 22 13667

BCLllA-12975 - CCGUAAGAAAAUGGGGGGGUAGG 23 13668

BCLllA-12976 - ACCGUAAGAAAAUGGGGGGGUAGG 24 13669

BCLllA-12977 - AAGUGGGUGUGCGUACGG 18 13670 BCLllA-12978 - GAAGUGGGUGUGCGUACGG 19 13671

BCLllA-10191 - GGAAGUGGGUGUGCGUACGG 20 13672

BCLllA-12979 - GGGAAGUGGGUGUGCGUACGG 21 13673

BCLllA-12980 - GGGGAAGUGGGUGUGCGUACGG 22 13674

BCLllA-12981 - AGGGGAAGUGGGUGUGCGUACGG 23 13675

BCLllA-12982 - GAGGGGAAGUGGGUGUGCGUACGG 24 13676

BCLllA-12983 - CGGUCAAGUGUGCAGCGG 18 13677

BCLllA-12984 - ACGGUCAAGUGUGCAGCGG 19 13678

BCLllA-12985 - CACGGUCAAGUGUGCAGCGG 20 13679

BCLllA-12986 - UCACGGUCAAGUGUGCAGCGG 21 13680

BCLllA-12987 - CUCACGGUCAAGUGUGCAGCGG 22 13681

BCLllA-12988 - GCUCACGGUCAAGUGUGCAGCGG 23 13682

BCLllA-12989 - CGCUCACGGUCAAGUGUGCAGCGG 24 13683

BCLllA-12990 - GAGCGAGCGCGGCGGCGG 18 13684

BCLllA-12991 - GGAGCGAGCGCGGCGGCGG 19 13685

BCLllA-10196 - GGGAGCGAGCGCGGCGGCGG 20 13686

BCLllA-12992 - GGGGAGCGAGCGCGGCGGCGG 21 13687

BCLllA-12993 - CGGGGAGCGAGCGCGGCGGCGG 22 13688

BCLllA-12994 - GCGGGGAGCGAGCGCGGCGGCGG 23 13689

BCLllA-12995 - CGCGGGGAGCGAGCGCGGCGGCGG 24 13690

BCLllA-12996 - CUGAGUCCGCGGAGUCGG 18 13691

BCLllA-12997 - CCUGAGUCCGCGGAGUCGG 19 13692

BCLllA-12998 - UCCUGAGUCCGCGGAGUCGG 20 13693

BCLllA-12999 - CUCCUGAGUCCGCGGAGUCGG 21 13694

BCLllA-13000 - GCUCCUGAGUCCGCGGAGUCGG 22 13695

BCLllA-13001 - CGCUCCUGAGUCCGCGGAGUCGG 23 13696

BCLllA-13002 - GCGCUCCUGAGUCCGCGGAGUCGG 24 13697

BCLllA-13003 - GAAAAUGGGGGGGUAGGG 18 13698

BCLllA-13004 - AGAAAAUGGGGGGGUAGGG 19 13699

BCLllA-10200 - AAGAAAAUGGGGGGGUAGGG 20 13700

BCLllA-13005 - UAAGAAAAUGGGGGGGUAGGG 21 13701

BCLllA-13006 - GUAAGAAAAUGGGGGGGUAGGG 22 13702

BCLllA-13007 - CGUAAGAAAAUGGGGGGGUAGGG 23 13703

BCLllA-13008 - CCGUAAGAAAAUGGGGGGGUAGGG 24 13704

BCLllA-13009 - AGGGGCCGCGGCGACGGG 18 13705

BCLllA-13010 - GAGGGGCCGCGGCGACGGG 19 13706

BCLllA-13011 - AGAGGGGCCGCGGCGACGGG 20 13707

BCLllA-13012 - GAGAGGGGCCGCGGCGACGGG 21 13708

BCLllA-13013 - GGAGAGGGGCCGCGGCGACGGG 22 13709

BCLllA-13014 - GGGAGAGGGGCCGCGGCGACGGG 23 13710

BCLllA-13015 - CGGGAGAGGGGCCGCGGCGACGGG 24 13711

BCLllA-13016 - GAGAGCCGUGGGACCGGG 18 13712 BCLllA-13017 - GGAGAGCCGUGGGACCGGG 19 13713

BCLllA-13018 - GGGAGAGCCGUGGGACCGGG 20 13714

BCLllA-13019 - GGGGAGAGCCGUGGGACCGGG 21 13715

BCLllA-13020 - CGGGGAGAGCCGUGGGACCGGG 22 13716

BCLllA-13021 - ACGGGGAGAGCCGUGGGACCGGG 23 13717

BCLllA-13022 - GACGGGGAGAGCCGUGGGACCGGG 24 13718

BCLllA-13023 - UAAAAAACGAUUCCCGGG 18 13719

BCLllA-13024 - CUAAAAAACGAUUCCCGGG 19 13720

BCLllA-13025 - UCUAAAAAACGAUUCCCGGG 20 13721

BCLllA-13026 - GUCUAAAAAACGAUUCCCGGG 21 13722

BCLllA-13027 - AGUCUAAAAAACGAUUCCCGGG 22 13723

BCLllA-13028 - AAGUCUAAAAAACGAUUCCCGGG 23 13724

BCLllA-13029 - CAAGUCUAAAAAACGAUUCCCGGG 24 13725

BCLllA-13030 - GGUCAAGUGUGCAGCGGG 18 13726

BCLllA-13031 - CGGUCAAGUGUGCAGCGGG 19 13727

BCLllA-10202 - ACGGUCAAGUGUGCAGCGGG 20 13728

BCLllA-13032 - CACGGUCAAGUGUGCAGCGGG 21 13729

BCLllA-13033 - UCACGGUCAAGUGUGCAGCGGG 22 13730

BCLllA-13034 - CUCACGGUCAAGUGUGCAGCGGG 23 13731

BCLllA-13035 - GCUCACGGUCAAGUGUGCAGCGGG 24 13732

BCLllA-13036 - GAGCGCGGCGGCGGCGGG 18 13733

BCLllA-13037 - CGAGCGCGGCGGCGGCGGG 19 13734

BCLllA-13038 - GCGAGCGCGGCGGCGGCGGG 20 13735

BCLllA-13039 - AGCGAGCGCGGCGGCGGCGGG 21 13736

BCLllA-13040 - GAGCGAGCGCGGCGGCGGCGGG 22 13737

BCLllA-13041 - GGAGCGAGCGCGGCGGCGGCGGG 23 13738

BCLllA-13042 - GGGAGCGAGCGCGGCGGCGGCGGG 24 13739

BCLllA-13043 - AGCGCGGCGGCGGCGGGG 18 13740

BCLllA-13044 - GAGCGCGGCGGCGGCGGGG 19 13741

BCLllA-10206 - CGAGCGCGGCGGCGGCGGGG 20 13742

BCLllA-13045 - GCGAGCGCGGCGGCGGCGGGG 21 13743

BCLllA-13046 - AGCGAGCGCGGCGGCGGCGGGG 22 13744

BCLllA-13047 - GAGCGAGCGCGGCGGCGGCGGGG 23 13745

BCLllA-13048 - GGAGCGAGCGCGGCGGCGGCGGGG 24 13746

BCLllA-13049 - CGUAAGAAAAUGGGGGGG 18 13747

BCLllA-13050 - CCGUAAGAAAAUGGGGGGG 19 13748

BCLllA-13051 - ACCGUAAGAAAAUGGGGGGG 20 13749

BCLllA-13052 - CACCGUAAGAAAAUGGGGGGG 21 13750

BCLllA-13053 - UCACCGUAAGAAAAUGGGGGGG 22 13751

BCLllA-13054 - CUCACCGUAAGAAAAUGGGGGGG 23 13752

BCLllA-13055 - ACUCACCGUAAGAAAAUGGGGGGG 24 13753

BCLllA-13056 - CACAUGCAAACCUGGGGG 18 13754 BCLllA-13057 - UCACAUGCAAACCUGGGGG 19 13755

BCLllA-10210 - CUCACAUGCAAACCUGGGGG 20 13756

BCLllA-13058 - ACUCACAUGCAAACCUGGGGG 21 13757

BCLllA-13059 - AACUCACAUGCAAACCUGGGGG 22 13758

BCLllA-13060 - CAACUCACAUGCAAACCUGGGGG 23 13759

BCLllA-13061 - ACAACUCACAUGCAAACCUGGGGG 24 13760

BCLllA-13062 - UCACAUGCAAACCUGGGG 18 13761

BCLllA-13063 - CUCACAUGCAAACCUGGGG 19 13762

BCLllA-13064 - ACUCACAUGCAAACCUGGGG 20 13763

BCLllA-13065 - AACUCACAUGCAAACCUGGGG 21 13764

BCLllA-13066 - CAACUCACAUGCAAACCUGGGG 22 13765

BCLllA-13067 - ACAACUCACAUGCAAACCUGGGG 23 13766

BCLllA-13068 - AACAACUCACAUGCAAACCUGGGG 24 13767

BCLllA-11486 - GAGUCCGCGUGUGUGGGG 18 13768

BCLllA-11487 - AGAGUCCGCGUGUGUGGGG 19 13769

BCLllA-9577 - UAGAGUCCGCGUGUGUGGGG 20 13770

BCLllA-11488 - UUAGAGUCCGCGUGUGUGGGG 21 13771

BCLllA-11489 - UUUAGAGUCCGCGUGUGUGGGG 22 13772

BCLllA-11490 - UUUUAGAGUCCGCGUGUGUGGGG 23 13773

BCLllA-11491 - AUUUUAGAGUCCGCGUGUGUGGGG 24 13774

BCLllA-11492 - AGAGUCCGCGUGUGUGGG 18 13775

BCLllA-11493 - UAGAGUCCGCGUGUGUGGG 19 13776

BCLllA-9769 - UUAGAGUCCGCGUGUGUGGG 20 13777

BCLllA-11494 - UUUAGAGUCCGCGUGUGUGGG 21 13778

BCLllA-11495 - UUUUAGAGUCCGCGUGUGUGGG 22 13779

BCLllA-11496 - AUUUUAGAGUCCGCGUGUGUGGG 23 13780

BCLllA-11497 - CAUUUUAGAGUCCGCGUGUGUGGG 24 13781

BCLllA-13069 - CCUGGGGGUGGGAGCUGG 18 13782

BCLllA-13070 - ACCUGGGGGUGGGAGCUGG 19 13783

BCLllA-10217 - AACCUGGGGGUGGGAGCUGG 20 13784

BCLllA-13071 - AAACCUGGGGGUGGGAGCUGG 21 13785

BCLllA-13072 - CAAACCUGGGGGUGGGAGCUGG 22 13786

BCLllA-13073 - GCAAACCUGGGGGUGGGAGCUGG 23 13787

BCLllA-13074 - UGCAAACCUGGGGGUGGGAGCUGG 24 13788

BCLllA-11498 - UAGAGUCCGCGUGUGUGG 18 13789

BCLllA-11499 - UUAGAGUCCGCGUGUGUGG 19 13790

BCLllA-9578 - UUUAGAGUCCGCGUGUGUGG 20 13791

BCLllA-11500 - UUUUAGAGUCCGCGUGUGUGG 21 13792

BCLllA-11501 - AUUUUAGAGUCCGCGUGUGUGG 22 13793

BCLllA-11502 - CAUUUUAGAGUCCGCGUGUGUGG 23 13794

BCLllA-11503 - UCAUUUUAGAGUCCGCGUGUGUGG 24 13795

BCLllA-13075 - ACUCACCGUAAGAAAAUG 18 13796 BCLllA-13076 - CACUCACCGUAAGAAAAUG 19 13797

BCLllA-10221 - CCACUCACCGUAAGAAAAUG 20 13798

BCLllA-13077 - CCCACU CACCG U AAG AAAAUG 21 13799

BCLllA-13078 - U CCCACU CACCG U AAG AAAAUG 22 13800

BCLllA-13079 - U U CCCACU CACCG U AAG AAAAUG 23 13801

BCLllA-13080 - CUUCCCACUCACCGUAAGAAAAUG 24 13802

BCLllA-13081 - AG U G AG AAAG U G G C AC U G 18 13803

BCLllA-13082 - UAGUGAGAAAGUGGCACUG 19 13804

BCLllA-10222 - AUAGUGAGAAAGUGGCACUG 20 13805

BCLllA-13083 - AAUAGUGAGAAAGUGGCACUG 21 13806

BCLllA-13084 - CAAUAGUGAGAAAGUGGCACUG 22 13807

BCLllA-13085 - ACAAUAGUGAGAAAGUGGCACUG 23 13808

BCLllA-13086 - CACAAUAGUGAGAAAGUGGCACUG 24 13809

BCLllA-13087 - ACCUGGGGGUGGGAGCUG 18 13810

BCLllA-13088 - AACCUGGGGGUGGGAGCUG 19 13811

BCLllA-13089 - AAACCUGGGGGUGGGAGCUG 20 13812

BCLllA-13090 - CAAACCUGGGGGUGGGAGCUG 21 13813

BCLllA-13091 - GCAAACCUGGGGGUGGGAGCUG 22 13814

BCLllA-13092 - UGCAAACCUGGGGGUGGGAGCUG 23 13815

BCLllA-13093 - AUGCAAACCUGGGGGUGGGAGCUG 24 13816

BCLllA-13094 - ACCUCCCCUCGCCCGCUG 18 13817

BCLllA-13095 - CACCUCCCCUCGCCCGCUG 19 13818

BCLllA-10224 - CCACCUCCCCUCGCCCGCUG 20 13819

BCLllA-13096 - CCCACCUCCCCUCGCCCGCUG 21 13820

BCLllA-13097 - UCCCACCUCCCCUCGCCCGCUG 22 13821

BCLllA-13098 - CUCCCACCUCCCCUCGCCCGCUG 23 13822

BCLllA-13099 - CCUCCCACCUCCCCUCGCCCGCUG 24 13823

BCLllA-13100 - UGGGGGUGGGAGCUGGUG 18 13824

BCLllA-13101 - CUGGGGGUGGGAGCUGGUG 19 13825

BCLllA-10228 - CCUGGGGGUGGGAGCUGGUG 20 13826

BCLllA-13102 - ACCUGGGGGUGGGAGCUGGUG 21 13827

BCLllA-13103 - AACCUGGGGGUGGGAGCUGGUG 22 13828

BCLllA-13104 - AAACCUGGGGGUGGGAGCUGGUG 23 13829

BCLllA-13105 - CAAACCUGGGGGUGGGAGCUGGUG 24 13830

BCLllA-11518 - UUUUAGAGUCCGCGUGUG 18 13831

BCLllA-11519 - AUUUUAGAGUCCGCGUGUG 19 13832

BCLllA-9581 - CAUUUUAGAGUCCGCGUGUG 20 13833

BCLllA-11520 - UCAUUUUAGAGUCCGCGUGUG 21 13834

BCLllA-11521 - UUCAUUUUAGAGUCCGCGUGUG 22 13835

BCLllA-11522 - UUUCAUUUUAGAGUCCGCGUGUG 23 13836

BCLllA-11523 - CUUUCAUUUUAGAGUCCGCGUGUG 24 13837

BCLllA-11524 - UUAGAGUCCGCGUGUGUG 18 13838 BCLllA-11525 - UUUAGAGUCCGCGUGUGUG 19 13839

BCLllA-9776 - UUUUAGAGUCCGCGUGUGUG 20 13840

BCLllA-11526 - AUUUUAGAGUCCGCGUGUGUG 21 13841

BCLllA-11527 - CAUUUUAGAGUCCGCGUGUGUG 22 13842

BCLllA-11528 - UCAUUUUAGAGUCCGCGUGUGUG 23 13843

BCLllA-11529 - UUCAUUUUAGAGUCCGCGUGUGUG 24 13844

BCLllA-13106 - CACUCACCGUAAGAAAAU 18 13845

BCLllA-13107 - CCACUCACCGUAAGAAAAU 19 13846

BCLllA-10232 - CCCACUCACCGUAAGAAAAU 20 13847

BCLllA-13108 - UCCCACUCACCGUAAGAAAAU 21 13848

BCLllA-13109 - U U CCCACU CACCG UAAGAAAAU 22 13849

BCLllA-13110 - CU U CCCACU CACCG UAAGAAAAU 23 13850

BCLllA-13111 - GCU U CCCACU CACCG UAAGAAAAU 24 13851

BCLllA-13112 - CGCUGCGGAGCUGUAACU 18 13852

BCLllA-13113 - CCGCUGCGGAGCUGUAACU 19 13853

BCLllA-10233 - CCCGCUGCGGAGCUGUAACU 20 13854

BCLllA-13114 - GCCCGCUGCGGAGCUGUAACU 21 13855

BCLllA-13115 - CGCCCGCUGCGGAGCUGUAACU 22 13856

BCLllA-13116 - UCGCCCGCUGCGGAGCUGUAACU 23 13857

BCLllA-13117 - CUCGCCCGCUGCGGAGCUGUAACU 24 13858

BCLllA-13118 - UAGUGAGAAAGUGGCACU 18 13859

BCLllA-13119 - AUAGUGAGAAAGUGGCACU 19 13860

BCLllA-13120 - AAUAGUGAGAAAGUGGCACU 20 13861

BCLllA-13121 - CAAUAGUGAGAAAGUGGCACU 21 13862

BCLllA-13122 - ACAAUAGUGAGAAAGUGGCACU 22 13863

BCLllA-13123 - CACAAUAGUGAGAAAGUGGCACU 23 13864

BCLllA-13124 - CCACAAUAGUGAGAAAGUGGCACU 24 13865

BCLllA-13125 - CGGUCCCUGGCUCGGCCU 18 13866

BCLllA-13126 - CCGGUCCCUGGCUCGGCCU 19 13867

BCLllA-10237 - CCCGGUCCCUGGCUCGGCCU 20 13868

BCLllA-13127 - CACCUCCCCUCGCCCGCU 18 13869

BCLllA-13128 - CCACCUCCCCUCGCCCGCU 19 13870

BCLllA-13129 - CCCACCUCCCCUCGCCCGCU 20 13871

BCLllA-13130 - UCCCACCUCCCCUCGCCCGCU 21 13872

BCLllA-13131 - CUCCCACCUCCCCUCGCCCGCU 22 13873

BCLllA-13132 - CCUCCCACCUCCCCUCGCCCGCU 23 13874

BCLllA-13133 - CCCUCCCACCUCCCCUCGCCCGCU 24 13875

BCLllA-13134 - CGAGCGCAGCCGCGGGCU 18 13876

BCLllA-13135 - CCGAGCGCAGCCGCGGGCU 19 13877

BCLllA-10241 - CCCGAGCGCAGCCGCGGGCU 20 13878

BCLllA-13136 - UCCCGAGCGCAGCCGCGGGCU 21 13879

BCLllA-13137 - UUCCCGAGCGCAGCCGCGGGCU 22 13880 BCLllA-13138 - UUUCCCGAGCGCAGCCGCGGGCU 23 13881

BCLllA-13139 - GUUUCCCGAGCGCAGCCGCGGGCU 24 13882

BCLllA-13140 - CUCCUGAGUCCGCGGAGU 18 13883

BCLllA-13141 - GCUCCUGAGUCCGCGGAGU 19 13884

BCLllA-10243 - CGCUCCUGAGUCCGCGGAGU 20 13885

BCLllA-13142 - GCGCUCCUGAGUCCGCGGAGU 21 13886

BCLllA-13143 - GGCGCUCCUGAGUCCGCGGAGU 22 13887

BCLllA-13144 - CGGCGCUCCUGAGUCCGCGGAGU 23 13888

BCLllA-13145 - CCGGCGCUCCUGAGUCCGCGGAGU 24 13889

BCLllA-13146 - AGUCAUCCCCACAAUAGU 18 13890

BCLllA-13147 - UAGUCAUCCCCACAAUAGU 19 13891

BCLllA-13148 - GUAGUCAUCCCCACAAUAGU 20 13892

BCLllA-13149 - AGUAGUCAUCCCCACAAUAGU 21 13893

BCLllA-13150 - AAGUAGUCAUCCCCACAAUAGU 22 13894

BCLllA-13151 - AAAGUAGUCAUCCCCACAAUAGU 23 13895

BCLllA-13152 - GAAAGUAGUCAUCCCCACAAUAGU 24 13896

BCLllA-13153 - UUGCUUCCCACUCACCGU 18 13897

BCLllA-13154 - GUUGCUUCCCACUCACCGU 19 13898

BCLllA-13155 - GGUUGCUUCCCACUCACCGU 20 13899

BCLllA-13156 - AGGUUGCUUCCCACUCACCGU 21 13900

BCLllA-13157 - GAGGUUGCUUCCCACUCACCGU 22 13901

BCLllA-13158 - GGAGGUUGCUUCCCACUCACCGU 23 13902

BCLllA-13159 - GGGAGGUUGCUUCCCACUCACCGU 24 13903

BCLllA-13160 - GGGGAAGUGGGUGUGCGU 18 13904

BCLllA-13161 - AGGGGAAGUGGGUGUGCGU 19 13905

BCLllA-13162 - GAGGGGAAGUGGGUGUGCGU 20 13906

BCLllA-13163 - GGAGGGGAAGUGGGUGUGCGU 21 13907

BCLllA-13164 - GGGAGGGGAAGUGGGUGUGCGU 22 13908

BCLllA-13165 - GGGGAGGGGAAGUGGGUGUGCGU 23 13909

BCLllA-13166 - CGGGGAGGGGAAGUGGGUGUGCGU 24 13910

BCLllA-13167 - GUAAGAAAAUGGGGGGGU 18 13911

BCLllA-13168 - CGUAAGAAAAUGGGGGGGU 19 13912

BCLllA-10248 - CCGUAAGAAAAUGGGGGGGU 20 13913

BCLllA-13169 - ACCGUAAGAAAAUGGGGGGGU 21 13914

BCLllA-13170 - CACCGUAAGAAAAUGGGGGGGU 22 13915

BCLllA-13171 - UCACCGUAAGAAAAUGGGGGGGU 23 13916

BCLllA-13172 - CUCACCGUAAGAAAAUGGGGGGGU 24 13917

BCLllA-13173 - ACAUGCAAACCUGGGGGU 18 13918

BCLllA-13174 - CACAUGCAAACCUGGGGGU 19 13919

BCLllA-10249 - UCACAUGCAAACCUGGGGGU 20 13920

BCLllA-13175 - CUCACAUGCAAACCUGGGGGU 21 13921

BCLllA-13176 - ACUCACAUGCAAACCUGGGGGU 22 13922 BCLllA-13177 - AACUCACAUGCAAACCUGGGGGU 23 13923

BCLllA-13178 - CAACUCACAUGCAAACCUGGGGGU 24 13924

BCLllA-13179 - CUGGGGGUGGGAGCUGGU 18 13925

BCLllA-13180 - CCUGGGGGUGGGAGCUGGU 19 13926

BCLllA-10250 - ACCUGGGGGUGGGAGCUGGU 20 13927

BCLllA-13181 - AACCUGGGGGUGGGAGCUGGU 21 13928

BCLllA-13182 - AAACCUGGGGGUGGGAGCUGGU 22 13929

BCLllA-13183 - CAAACCUGGGGGUGGGAGCUGGU 23 13930

BCLllA-13184 - GCAAACCUGGGGGUGGGAGCUGGU 24 13931

BCLllA-11572 - AUUUUAGAGUCCGCGUGU 18 13932

BCLllA-11573 - CAUUUUAGAGUCCGCGUGU 19 13933

BCLllA-11574 - UCAUUUUAGAGUCCGCGUGU 20 13934

BCLllA-11575 - UUCAUUUUAGAGUCCGCGUGU 21 13935

BCLllA-11576 - UUUCAUUUUAGAGUCCGCGUGU 22 13936

BCLllA-11577 - CUUUCAUUUUAGAGUCCGCGUGU 23 13937

BCLllA-11578 - UCUUUCAUUUUAGAGUCCGCGUGU 24 13938

BCLllA-13185 - GCGUACGGAGGAGGGUGU 18 13939

BCLllA-13186 - UGCGUACGGAGGAGGGUGU 19 13940

BCLllA-13187 - GUGCGUACGGAGGAGGGUGU 20 13941

BCLllA-13188 - UGUGCGUACGGAGGAGGGUGU 21 13942

BCLllA-13189 - GUGUGCGUACGGAGGAGGGUGU 22 13943

BCLllA-13190 - GGUGUGCGUACGGAGGAGGGUGU 23 13944

BCLllA-13191 - GGGUGUGCGUACGGAGGAGGGUGU 24 13945

BCLllA-11579 - UUUAGAGUCCGCGUGUGU 18 13946

BCLllA-11580 - UUUUAGAGUCCGCGUGUGU 19 13947

BCLllA-9586 - AUUUUAGAGUCCGCGUGUGU 20 13948

BCLllA-11581 - CAUUUUAGAGUCCGCGUGUGU 21 13949

BCLllA-11582 - UCAUUUUAGAGUCCGCGUGUGU 22 13950

BCLllA-11583 - UUCAUUUUAGAGUCCGCGUGUGU 23 13951

BCLllA-11584 - UUUCAUUUUAGAGUCCGCGUGUGU 24 13952

BCLllA-13192 - GACUUGGGCGCUGCCCUU 18 13953

BCLllA-13193 - AGACUUGGGCGCUGCCCUU 19 13954

BCLllA-13194 - GAGACUUGGGCGCUGCCCUU 20 13955

BCLllA-13195 - GGAGACUUGGGCGCUGCCCUU 21 13956

BCLllA-13196 - UGGAGACUUGGGCGCUGCCCUU 22 13957

BCLllA-13197 - CUGGAGACUUGGGCGCUGCCCUU 23 13958

BCLllA-13198 - CCUGGAGACUUGGGCGCUGCCCUU 24 13959

BCLllA-13199 - GGUCCCUGGCUCGGCCUU 18 13960

BCLllA-13200 - CGGUCCCUGGCUCGGCCUU 19 13961

BCLllA-10256 - CCGGUCCCUGGCUCGGCCUU 20 13962

BCLllA-13201 - AAGAGGUGAGACUGGCUU 18 13963

BCLllA-13202 - AAAGAGGUGAGACUGGCUU 19 13964 BCLllA-13203 - AAAAGAGGUGAGACUGGCUU 20 13965

BCLllA-13204 - GAAAAGAGGUGAGACUGGCUU 21 13966

BCLllA-13205 - AGAAAAGAGGUGAGACUGGCUU 22 13967

BCLllA-13206 - GAGAAAAGAGGUGAGACUGGCUU 23 13968

BCLllA-13207 - GGAGAAAAGAGGUGAGACUGGCUU 24 13969

BCLllA-13208 - AUGAACAAUGCUAAGGUU 18 13970

BCLllA-13209 - AAUGAACAAUGCUAAGGUU 19 13971

BCLllA-13210 - UAAUGAACAAUGCUAAGGUU 20 13972

BCLllA-13211 - AUAAUGAACAAUGCUAAGGUU 21 13973

BCLllA-13212 - AAUAAUGAACAAUGCUAAGGUU 22 13974

BCLllA-13213 - AAAUAAUGAACAAUGCUAAGGUU 23 13975

BCLllA-13214 - AAAAUAAUGAACAAUGCUAAGGUU 24 13976

BCLllA-13215 - GCCGCUU UAUUUCUCUUU 18 13977

BCLllA-13216 - CGCCGCUUUAUUUCUCUUU 19 13978

BCLllA-13217 - CCGCCGCUUUAUUUCUCUUU 20 13979

BCLllA-13218 - UCCGCCGCUUUAU UUCUCUUU 21 13980

BCLllA-13219 - UUCCGCCGCUU UAUUUCUCUUU 22 13981

BCLllA-13220 - UUUCCGCCGCU UUAUUUCUCUUU 23 13982

BCLllA-13221 - CUU UCCGCCGCUUUAUU UCUCUUU 24 13983

Table 17A provides exemplary targeting domains for knocking down the BCLl 1 A 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) 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 eiCas9 molecule or eiCas9 fusion protein (e.g., an eiCas9 fused to a transcription repressor domain) to alter the BCLl 1 A gene (e.g., reduce or eliminate BCLl 1 A gene expression, BCLl 1 A protein function, or the level of BCLl 1 A protein). One or more gRNA may be used to target an eiCas9 to the promoter region of the BCLl 1 A gene.

Table 17A

BCLllA-9482 + U UAAGUGCUGGGGU UUG 17 13989

BCLllA-13225 + CACGCGGACUCUAAAAU 17 13990

BCLllA-13226 + AAUUGUGGGAGAGCCGU 17 13991

BCLllA-13227 - GAUGUGUGUCCAUUGGU 17 13992

BCLllA-13228 + UGCACACACCCCUCUCUCCC 20 13993

BCLllA-9487 + UUACUUACGCGAGAAUUCCC 20 13994

BCLllA-13229 + CACCCCUCUCUCCCCCUCGC 20 13995

BCLllA-13230 + GCU UCUAGUCCUGCGCGCUC 20 13996

BCLllA-9738 - CACUUGAACUUGCAGCUCAG 20 13997

BCLllA-9491 + UGCUUAAGUGCUGGGGUUUG 20 13998

BCLllA-13231 + AUGAAUUGUGGGAGAGCCGU 20 13999

BCLllA-11567 - CCUGAUGUGUGUCCAU UGGU 20 14000

Table 17B provides exemplary targeting domains for knocking down the BCLl 1 A 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). 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 eiCas9 molecule or eiCas9 fusion protein (e.g., an eiCas9 fused to a transcription repressor domain) to alter the BCLl 1 A gene (e.g., reduce or eliminate BCLl 1A gene expression, BCLl 1A protein function, or the level of BCLl 1 A protein). One or more gRNA may be used to target an eiCas9 to the promoter region of the BCLl 1A gene.

Table 17B

Table 17C provides exemplary targeting domains for knocking down the BCLl 1 A gene selected according to the third 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. meningitidis eiCas9 molecule or eiCas9 fusion protein (e.g., an eiCas9 fused to a transcription repressor domain) to alter the BCLl 1 A gene (e.g., reduce or eliminate BCLl 1A gene expression, BCLl 1A protein function, or the level of BCLl 1A protein). One or more gRNA may be used to target an eiCas9 to the promoter region of the BCLl 1 A gene.

Table 17C

Table 18A provides exemplary targeting domains for removing (e.g., deleting) the enhancer region of the BCLl 1 A gene selected according to the first tier parameters. The targeting domains bind within a region 5' (51.5 to 51.7kb downstream of TSS) or 3' (65.1 to 65.3kb downstream of TSS), have a high level of orthogonality and starts with 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 18A

Table 18B provides exemplary targeting domains for removing (e.g., deleting) the enhancer region the BCL11A gene selected according to the second tier parameters. The targeting domains bind within a region 5' (51.5 to 51.7kb downstream of TSS) or 3' (65.1 to 65.3kb downstream of 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 Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 18B

BCLllA-13270 - UUGGAAUGUAGAGAGGCAGA 20 5' 14045

BCLllA-13271 + AUUAUUUUACUAGUGAAUUA 20 5' 14046

BCLllA-13272 + AAAAU U U AAG ACGGG AAAAC 20 5' 14047

BCLllA-13273 + CU CACAU AAAAAU U U AAG AC 20 5' 14048

BCLllA-13274 + UACACAACUUGUGUUGCACU 20 5' 14049

BCLllA-13275 - UAAGAAAGCAGUGUAAGGCU 20 5' 14050

BCLllA-13276 - AUUAGAAUAAAAGGCUGUUU 20 5' 14051

BCLllA-13277 - U AU U UACAG CCAU AACA 17 3' 14052

BCLllA-13278 + AUACUUACUGUACUGCA 17 3' 14053

BCLllA-13279 + CACUGGAAACCCUGUUA 17 3' 14054

BCLllA-13280 - CUAUUUACAGCCAUAAC 17 3' 14055

BCLllA-13281 + CUACUUAUACAAUUCAC 17 3' 14056

BCLllA-13282 + AAUACUUACUGUACUGC 17 3' 14057

BCLllA-13283 + UACUUACUGUACUGCAG 17 3' 14058

BCLllA-13284 + UGUACUGCAGGGGAAUU 17 3' 14059

BCLllA-13285 - UGGGUAGCAGUGGCUUU 17 3' 14060

BCLllA-13286 - UGGCUUUAGGCUGUUUU 17 3' 14061

BCLllA-13287 - AACUAUUUACAGCCAUAACA 20 3' 14062

BCLllA-13288 + AAAAUACUUACUGUACUGCA 20 3' 14063

BCLllA-13289 + AUUCACUGGAAACCCUGUUA 20 3' 14064

BCLllA-13290 - AAACUAUUUACAGCCAUAAC 20 3' 14065

BCLllA-13291 + AAAUACUUACUGUACUGCAG 20 3' 14066

BCLllA-13292 + UACUGUACUGCAGGGGAAUU 20 3' 14067

BCLllA-13293 - UUAGGCUGUUUUUGGAUCUU 20 3' 14068

BCLllA-13294 - CAGUGGCUUUAGGCUGUUUU 20 3' 14069

Table 18C provides exemplary targeting domains for removing (e.g., deleting) the enhancer region the BCLl 1A gene selected according to the third tier parameters. The targeting domains bind within a region 5' (51.5 to 51.7kb downstream of TSS) or 3' (65.1 to 65.3kb downstream of TSS) and starts with 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 18C

BCLllA-13297 - GUAUUUUCUUUCAUUGG 17 3' 14072

BCLllA-13298 - GUAAGUAUUUUCUU UCAUUG 20 3' 14073

Table 18D provides exemplary targeting domains for removing (e.g., deleting) the enhancer region the BCLl 1A gene selected according to the fourth tier parameters. The targeting domains bind within a region 5' (51.5 to 51.7kb downstream of TSS) or 3' (65.1 to 65.3kb downstream of 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 Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 18D

Table 18E provides targeting domains for removing (e.g., deleting) the enhancer region the BCLl 1A gene by dual targeting (e.g., dual double strand cleavage). It is contemplated herein that an upstream gRNA can be paired with a downstream gRNA to guide Cas9 nuclease pairs. Exemplary nickase pairs include a targeting domain from Group A and a second targeting domain from Group B, or include a targeting domain from Group C and a second targeting domain from Group D. It is contemplated herein that in an embodiment a targeting domain of Group A can be combined with any of the targeting domains of Group B; in an embodiment a targeting domain of Group C can be combined with any of the targeting domains of Group D. For example, BCLl lA- 13271 or BCLl lA-13264 can be combined with BCLl lA-13276; or BCLl 1A-13262 or BCLl 1A-13282 can be combined with BCLl 1A-13290 or BCLl 1 A- 13280. Table 18E

Table 19A provides exemplary targeting domains for removing (e.g., deleting) the enhancer region the BCLl 1A gene selected according to the first tier parameters. The targeting domains bind within a region 5' (51.5 to 51.7kb downstream of TSS) or 3' (65.1 to 65.3kb downstream of TSS), have a high level of orthogonality, and start with 5'G. The 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 19A

BCLllA-13325 - GCAGUGGCUUUAGGCUGUUU 20 3' 14100

BCLllA-13326 - GUAGCAGUGGCUUUAGGCUGUUU 23 3' 14101

BCLllA-13327 - GGUAGCAGUGGCUUUAGGCUGUUU 24 3' 14102

Table 19B provides exemplary targeting domains for removing (e.g., deleting) the enhancer region the BCL11A gene selected according to the second tier parameters. The targeting domains bind within a region 5' (51.5 to 51.7kb downstream of TSS) or 3' (65.1 to 65.3kb downstream of TSS) and have a high level of orthogonality, and the 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 19B

BCLllA-13350 - AUAAU U AG AAU AAAAGG CUG U U U 23 5' 14125

BCLllA-13351 - AAUAAU U AG AAU AAAAGG CUG U U U 24 5' 14126

BCLllA-13352 + AUACUUACUGUACUGCAG 18 3' 14127

BCLllA-13353 + AAUACUUACUGUACUGCAG 19 3' 14128

BCLllA-13354 + AAAUACUUACUGUACUGCAG 20 3' 14129

BCLllA-13355 - AACUAUUUACAGCCAUAA 18 3' 14130

BCLllA-13356 - AAACUAU U UACAG CCAUAA 19 3' 14131

BCLllA-13357 - CAAACU AU U UACAG CCAUAA 20 3' 14132

BCLllA-13358 - AGCAAACUAUUUACAGCCAUAA 22 3' 14133

BCLllA-13359 - AAGCAAACUAUUUACAGCCAUAA 23 3' 14134

BCLllA-13360 - AGCCAUAACAGGGUUUCCA 19 3' 14135

BCLllA-13361 - CAGCCAUAACAGGGUU UCCA 20 3' 14136

BCLllA-13362 - ACAGCCAUAACAGGGUU UCCA 21 3' 14137

BCLllA-13363 - UACAGCCAUAACAGGGU UUCCA 22 3' 14138

BCLllA-13364 - U U ACAGCCAU AACAGGG U U U CCA 23 3' 14139

BCLllA-13365 - U U U ACAGCCAU AACAGGG U U U CCA 24 3' 14140

BCLllA-13366 - UGAAUUGUAUAAGUAGCA 18 3' 14141

BCLllA-13367 - AGUGAAUUGUAUAAGUAGCA 20 3' 14142

BCLllA-13368 - CAGUGAAUUGUAUAAGUAGCA 21 3' 14143

BCLllA-13369 - CCAGUGAAUUGUAUAAGUAGCA 22 3' 14144

BCLllA-13370 - UCCAGUGAAUUGUAUAAGUAGCA 23 3' 14145

BCLllA-13371 - U UCCAGUGAAUUGUAUAAGUAGCA 24 3' 14146

BCLllA-13372 - CAAAACU AG AAAG U U U U A 18 3' 14147

BCLllA-13373 - AGCAAAACU AG AAAG U U U U A 20 3' 14148

BCLllA-13374 - AGUGGCUUUAGGCUGUUU 18 3' 14149

BCLllA-13375 - CAGUGGCUUUAGGCUGUUU 19 3' 14150

BCLllA-13376 - AGCAGUGGCUUUAGGCUGUUU 21 3' 14151

BCLllA-13377 - UAGCAGUGGCUU UAGGCUGUUU 22 3' 14152

Table 19C provides exemplary targeting domains for removing (e.g., deleting) the enhancer region the BCLl 1A gene selected according to the third tier parameters. The targeting domains bind within a region 5' (51.5 to 51.7kb downstream of TSS) or 3' (65.1 to 65.3kb downstream of TSS) and start with 5'G. The 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 19C

Target SEQ ID

DNA 5' or

gRNA Name Targeting Domain Site NO

Strand 3'

Length

BCLllA-13378 + GAAAAUACUUACUGUACUGCAG 22 3' 14153

BCLllA-13379 - G U U A AG C A A A AC U AG A A AG U U U U A 24 3' 14154

Table 19D provides exemplary targeting domains for removing (e.g., deleting) the enhancer region the BCLl 1A gene selected according to the second tier parameters. The targeting domains bind within a region 5' (51.5 to 51.7kb downstream of TSS) or 3' (65.1 to 65.3kb downstream of TSS), and the 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 19D

Table 19E provides exemplary targeting domains for removing (e.g., deleting) the enhancer region the BCLl 1A gene selected according to the third tier parameters. The targeting domains bind within a region 5' (51.5 to 51.7kb downstream of TSS) or 3' (65.1 to 65.3kb downstream of TSS), and the 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 19E

BCLllA-13427 + GCUCAUCUCACAUAAAAAUUUAAG 24 5' 14202

BCLllA-13428 + CAACUUGUGUUGCACUAG 18 5' 14203

BCLllA-13429 + ACAACUUGUGUUGCACUAG 19 5' 14204

BCLllA-13430 + CA CAACUUGUGUUGCACUAG 20 5' 14205

BCLllA-13431 + ACACAACUUGUGUUGCACUAG 21 5' 14206

BCLllA-13432 + UACACAACUUGUGU UGCACUAG 22 5' 14207

BCLllA-13433 + CUACACAACUUGUGUUGCACUAG 23 5' 14208

BCLllA-13434 + UCUACACAACUUGUGUUGCACUAG 24 5' 14209

BCLllA-13435 + AACAGGAAGAUGCAUUCU 18 5' 14210

BCLllA-13436 + AAACAGGAAGAUGCAUUCU 19 5' 14211

BCLllA-13437 + AAAACAGGAAGAUGCAUUCU 20 5' 14212

BCLllA-13438 + GAAAACAGGAAGAUGCAUUCU 21 5' 14213

BCLllA-13439 + GGAAAACAGGAAGAUGCAUUCU 22 5' 14214

BCLllA-13440 + GGGAAAACAGGAAGAUGCAUUCU 23 5' 14215

BCLllA-13441 + CG G G A A A AC AG GAAGAUGCAUUCU 24 5' 14216

BCLllA-13442 + U UAUUUUACUAGUGAAUU 18 5' 14217

BCLllA-13443 + AUUAUUUUACUAGUGAAUU 19 5' 14218

BCLllA-13444 + AAUUAUUUUACUAGUGAAUU 20 5' 14219

BCLllA-13445 + UAAUUAUUUUACUAGUGAAUU 21 5' 14220

BCLllA-13446 + CUAAUUAUUUUACUAGUGAAUU 22 5' 14221

BCLllA-13447 + UCUAAUUAUUUUACUAGUGAAUU 23 5' 14222

BCLllA-13448 + UUCUAAUUAUUUUACUAGUGAAUU 24 5' 14223

BCLllA-13449 + AAAACAGGAAGAUGCAUU 18 5' 14224

BCLllA-13450 + GAAAACAGGAAGAUGCAUU 19 5' 14225

BCLllA-13451 + GG AAAACAGGAAGAUGCAUU 20 5' 14226

BCLllA-13452 + GGGAAAACAGGAAGAUGCAUU 21 5' 14227

BCLllA-13453 + CGGGAAAACAGGAAGAUGCAUU 22 5' 14228

BCLllA-13454 + ACGGGAAAACAGGAAGAUGCAUU 23 5' 14229

BCLllA-13455 + GACGGGAAAACAGGAAGAUGCAUU 24 5' 14230

BCLllA-13456 - U UGGAAUGUAGAGAGGCA 18 5' 14231

BCLllA-13457 - U UUGGAAUGUAGAGAGGCA 19 5' 14232

BCLllA-13458 - U UUUGGAAUGUAGAGAGGCA 20 5' 14233

BCLllA-13459 - GUUUUGGAAUGUAGAGAGGCA 21 5' 14234

BCLllA-13460 - UGUUUUGGAAUGUAGAGAGGCA 22 5' 14235

BCLllA-13461 - CUGUUUUGGAAUGUAGAGAGGCA 23 5' 14236

BCLllA-13462 - GCUGUUUUGGAAUGUAGAGAGGCA 24 5' 14237

BCLllA-13463 - CAACACAAGUUGUGUAGA 18 5' 14238

BCLllA-13464 - GCAACACAAGUUGUGUAGA 19 5' 14239

BCLllA-13465 - UGCAACACAAGUUGUGUAGA 20 5' 14240

BCLllA-13466 - G U G C AACAC AAG UUGUGUAGA 21 5' 14241

BCLllA-13467 - AGUGCAACACAAGUUGUGUAGA 22 5' 14242

BCLllA-13468 - U AG U G C A AC AC A AG UUGUGUAGA 23 5' 14243 BCLllA-13469 - C U AG U G C AACAC AAG UUGUGUAGA 24 5' 14244

BCLllA-13470 - AGGCUGUUUUGGAAUGUA 18 5' 14245

BCLllA-13471 - AAGGCUGUUUUGGAAUGUA 19 5' 14246

BCLllA-13472 - AAAGGCUGUUUUGGAAUGUA 20 5' 14247

BCLllA-13473 - AAAAGGCUGUUUUGGAAUGUA 21 5' 14248

BCLllA-13474 - UAAAAGGCUGUUUUGGAAUGUA 22 5' 14249

BCLllA-13475 - AUAAAAGGCUGUUUUGGAAUGUA 23 5' 14250

BCLllA-13476 - AAUAAAAGGCUGUUUUGGAAUGUA 24 5' 14251

BCLllA-13477 - UGGAAUGUAGAGAGGCAG 18 5' 14252

BCLllA-13478 - UUGGAAUGUAGAGAGGCAG 19 5' 14253

BCLllA-13479 - UUUGGAAUGUAGAGAGGCAG 20 5' 14254

BCLllA-13480 - UUUUGGAAUGUAGAGAGGCAG 21 5' 14255

BCLllA-13481 - GU UUUGGAAUGUAGAGAGGCAG 22 5' 14256

BCLllA-13482 - UGUUUUGGAAUGUAGAGAGGCAG 23 5' 14257

BCLllA-13483 - CUGUUUUGGAAUGUAGAGAGGCAG 24 5' 14258

BCLllA-13484 - CUUAAAUUUUUAUGUGAG 18 5' 14259

BCLllA-13485 - UCUUAAAUUUUUAUGUGAG 19 5' 14260

BCLllA-13486 - GUCUUAAAUUUUUAUGUGAG 20 5' 14261

BCLllA-13487 - CGUCUUAAAUUUUUAUGUGAG 21 5' 14262

BCLllA-13488 - CCGUCUUAAAUUUUUAUGUGAG 22 5' 14263

BCLllA-13489 - CCCGUCUUAAAUUUUUAUGUGAG 23 5' 14264

BCLllA-13490 - UCCCGUCUUAAAUUUUUAUGUGAG 24 5' 14265

BCLllA-13491 - U A AG A A AG C AG U G U A AG G 18 5' 14266

BCLllA-13492 - U U A AG A A AG C AG U G U A AG G 19 5' 14267

BCLllA-13493 - AUUAAGAAAGCAGUGUAAGG 20 5' 14268

BCLllA-13494 - A A U U A AG A A AG C AG U G U A AG G 21 5' 14269

BCLllA-13495 - U A A U U A AG A A AG C AG U G U A AG G 22 5' 14270

BCLllA-13496 - GUAAU U AAG AAAGCAG UG U AAGG 23 5' 14271

BCLllA-13497 - U G U A A U U A AG A A AG CAGUGUAAGG 24 5' 14272

BCLllA-13498 - UUUUGGAAUGUAGAGAGG 18 5' 14273

BCLllA-13499 - GUUUUGGAAUGUAGAGAGG 19 5' 14274

BCLllA-13500 - UGUUUUGGAAUGUAGAGAGG 20 5' 14275

BCLllA-13501 - CUGUUUUGGAAUGUAGAGAGG 21 5' 14276

BCLllA-13502 - GCUGUUUUGGAAUGUAGAGAGG 22 5' 14277

BCLllA-13503 - GGCUGUUUUGGAAUGUAGAGAGG 23 5' 14278

BCLllA-13504 - AGGCUGUUUUGGAAUGUAGAGAGG 24 5' 14279

BCLllA-13505 - AAAGGCUGUUUUGGAAUG 18 5' 14280

BCLllA-13506 - AAAAGGCUGUUUUGGAAUG 19 5' 14281

BCLllA-13507 - UAAAAGGCUGUUUUGGAAUG 20 5' 14282

BCLllA-13508 - AUAAAAGGCUGUUUUGGAAUG 21 5' 14283

BCLllA-13509 - AAUAAAAGGCUGUUUUGGAAUG 22 5' 14284

BCLllA-13510 - GAAUAAAAGGCUGUUUUGGAAUG 23 5' 14285 BCLllA-13511 - AGAAUAAAAGGCUGUUUUGGAAUG 24 5' 14286

BCLllA-13512 - AG U G CAAC ACAAG U U G U G 18 5' 14287

BCLllA-13513 - U AG U G CAAC ACAAG U U G U G 19 5' 14288

BCLllA-13514 - CUAGUGCAACACAAGUUGUG 20 5' 14289

BCLllA-13515 - CCUAGUGCAACACAAGU UGUG 21 5' 14290

BCLllA-13516 - ACCUAGUGCAACACAAGUUGUG 22 5' 14291

BCLllA-13517 - CACCUAGUGCAACACAAGUUGUG 23 5' 14292

BCLllA-13518 - UCACCUAGUGCAACACAAGUUGUG 24 5' 14293

BCLllA-13519 - CCCGUCUUAAAUUUUUAU 18 5' 14294

BCLllA-13520 - UCCCGUCUUAAAUUUU UAU 19 5' 14295

BCLllA-13521 - UUCCCGUCUUAAAUUU UUAU 20 5' 14296

BCLllA-13522 - U UUCCCGUCUUAAAUUUUUAU 21 5' 14297

BCLllA-13523 - U UUUCCCGUCUUAAAUUUUUAU 22 5' 14298

BCLllA-13524 - GU UUUCCCGUCUUAAAUUUUUAU 23 5' 14299

BCLllA-13525 - UGUUUUCCCGUCUUAAAUUUUUAU 24 5' 14300

BCLllA-13526 - GAGCACACUGCUGUAAUU 18 5' 14301

BCLllA-13527 - UGAGCACACUGCUGUAAUU 19 5' 14302

BCLllA-13528 - AUGAGCACACUGCUGUAAUU 20 5' 14303

BCLllA-13529 - GAUGAGCACACUGCUGUAAUU 21 5' 14304

BCLllA-13530 - AGAUGAGCACACUGCUGUAAUU 22 5' 14305

BCLllA-13531 - GAGAUGAGCACACUGCUGUAAUU 23 5' 14306

BCLllA-13532 - UGAGAUGAGCACACUGCUGUAAUU 24 5' 14307

BCLllA-13533 - U UAGAAUAAAAGGCUGUU 18 5' 14308

BCLllA-13534 - AU U AG AAU AAAAGG CUG U U 19 5' 14309

BCLllA-13535 - AAUUAGAAUAAAAGGCUGUU 20 5' 14310

BCLllA-13536 - U AAU U AG AAU AAAAGG CUG U U 21 5' 14311

BCLllA-13537 - AUAAUUAGAAUAAAAGGCUGUU 22 5' 14312

BCLllA-13538 - AAU AAU U AG AAU AAAAGG CUG U U 23 5' 14313

BCLllA-13539 - AAAUAAUUAGAAUAAAAGGCUGUU 24 5' 14314

BCLllA-13540 + UUUCAUUUUUUGCUGACA 18 3' 14315

BCLllA-13541 + GUUUCAUUUU UUGCUGACA 19 3' 14316

BCLllA-13542 + UGUUUCAUUU UUUGCUGACA 20 3' 14317

BCLllA-13543 + UUGUUUCAUU UUUUGCUGACA 21 3' 14318

BCLllA-13544 + UUUGUUUCAU UUUUUGCUGACA 22 3' 14319

BCLllA-13545 + UUUUGUUUCAUUUUUUGCUGACA 23 3' 14320

BCLllA-13546 + UUUUUGUUUCAUUUUUUGCUGACA 24 3' 14321

BCLllA-13547 + AAUAGUUUGCUUCCCCCA 18 3' 14322

BCLllA-13548 + AAAUAGUUUGCUUCCCCCA 19 3' 14323

BCLllA-13549 + UAAAUAGUUUGCUUCCCCCA 20 3' 14324

BCLllA-13550 + GUAAAUAGUUUGCUUCCCCCA 21 3' 14325

BCLllA-13551 + UGUAAAUAGUUUGCUUCCCCCA 22 3' 14326

BCLllA-13552 + CUGUAAAUAGUUUGCUUCCCCCA 23 3' 14327 BCLllA-13553 + GCUGUAAAUAGUUUGCUUCCCCCA 24 3' 14328

BCLllA-13554 + AAUACUUACUGUACUGCA 18 3' 14329

BCLllA-13555 + AAAUACUUACUGUACUGCA 19 3' 14330

BCLllA-13556 + AAAAUACUUACUGUACUGCA 20 3' 14331

BCLllA-13557 + GAAAAUACUUACUGUACUGCA 21 3' 14332

BCLllA-13558 + AGAAAAUACUUACUGUACUGCA 22 3' 14333

BCLllA-13559 + AAGAAAAUACUUACUGUACUGCA 23 3' 14334

BCLllA-13560 + AAAGAAAAUACUUACUGUACUGCA 24 3' 14335

BCLllA-13561 + UGCUACUUAUACAAU UCA 18 3' 14336

BCLllA-13562 + GUGCUACUUAUACAAUUCA 19 3' 14337

BCLllA-13563 + AGUGCUACUUAUACAAUUCA 20 3' 14338

BCLllA-13564 + CAGUGCUACUUAUACAAUUCA 21 3' 14339

BCLllA-13565 + UCAGUGCUACUUAUACAAUUCA 22 3' 14340

BCLllA-13566 + CUCAGUGCUACUUAUACAAUUCA 23 3' 14341

BCLllA-13567 + ACUCAGUGCUACUUAUACAAUUCA 24 3' 14342

BCLllA-13568 + GUUUGCUUCCCCCAAUGA 18 3' 14343

BCLllA-13569 + AGUUUGCUUCCCCCAAUGA 19 3' 14344

BCLllA-13570 + UAGUUUGCUUCCCCCAAUGA 20 3' 14345

BCLllA-13571 + AUAGUUUGCUUCCCCCAAUGA 21 3' 14346

BCLllA-13572 + AAUAGUUUGCUUCCCCCAAUGA 22 3' 14347

BCLllA-13573 + AAAUAGUUUGCUUCCCCCAAUGA 23 3' 14348

BCLllA-13574 + UAAAUAGUUUGCUUCCCCCAAUGA 24 3' 14349

BCLllA-13575 + UUUCUAGUUU UGCUUAAC 18 3' 14350

BCLllA-13576 + CUUUCUAGU UUUGCUUAAC 19 3' 14351

BCLllA-13577 + ACUUUCUAGUUUUGCU UAAC 20 3' 14352

BCLllA-13578 + AACUUUCUAGUUU UGCUUAAC 21 3' 14353

BCLllA-13579 + AAACUUUCUAGUUUUGCUUAAC 22 3' 14354

BCLllA-13580 + AAAACUUUCUAGUUUUGCUUAAC 23 3' 14355

BCLllA-13581 + UAAAACUUUCUAGUUU UGCUUAAC 24 3' 14356

BCLllA-13582 + GCUACUUAUACAAUUCAC 18 3' 14357

BCLllA-13583 + UGCUACUUAUACAAUUCAC 19 3' 14358

BCLllA-13584 + GUGCUACUUAUACAAUUCAC 20 3' 14359

BCLllA-13585 + AGUGCUACUUAUACAAU UCAC 21 3' 14360

BCLllA-13586 + CAGUGCUACUUAUACAAUUCAC 22 3' 14361

BCLllA-13587 + UCAGUGCUACUUAUACAAUUCAC 23 3' 14362

BCLllA-13588 + CUCAGUGCUACUUAUACAAUUCAC 24 3' 14363

BCLllA-13589 + AAAUACUUACUGUACUGC 18 3' 14364

BCLllA-13590 + AAAAUACUUACUGUACUGC 19 3' 14365

BCLllA-13591 + GAAAAUACUUACUGUACUGC 20 3' 14366

BCLllA-13592 + AGAAAAUACUUACUGUACUGC 21 3' 14367

BCLllA-13593 + AAGAAAAUACUUACUGUACUGC 22 3' 14368

BCLllA-13594 + AAAGAAAAUACUUACUGUACUGC 23 3' 14369 BCLllA-13595 + GAAAGAAAAUACUUACUGUACUGC 24 3' 14370

BCLllA-13596 + AAAAUACUUACUGUACUG 18 3' 14371

BCLllA-13597 + GAAAAUACUUACUGUACUG 19 3' 14372

BCLllA-13598 + AGAAAAUACUUACUGUACUG 20 3' 14373

BCLllA-13599 + AAGAAAAUACUUACUGUACUG 21 3' 14374

BCLllA-13600 + AAAGAAAAUACUUACUGUACUG 22 3' 14375

BCLllA-13601 + GAAAGAAAAUACUUACUGUACUG 23 3' 14376

BCLllA-13602 + UGAAAGAAAAUACUUACUGUACUG 24 3' 14377

BCLllA-13603 - GUUCUGUGUCAG C A A A A A 18 3' 14378

BCLllA-13604 - AGUUCUGUGUCAGCAAAAA 19 3' 14379

BCLllA-13605 - GAGUUCUGUGUCAGCAAAAA 20 3' 14380

BCLllA-13606 - UGAGUUCUGUGUCAGCAAAAA 21 3' 14381

BCLllA-13607 - CUGAGUUCUGUGUCAGCAAAAA 22 3' 14382

BCLllA-13608 - ACUGAGUUCUGUGU CAG C AAAAA 23 3' 14383

BCLllA-13609 - CACUGAGUUCUGUGU CAG C AAAAA 24 3' 14384

BCLllA-13610 - AGUAAGUAUUUUCUUUCA 18 3' 14385

BCLllA-13611 - CAGUAAGUAUUUUCUUUCA 19 3' 14386

BCLllA-13612 - ACAGUAAGUAUUUUCUUUCA 20 3' 14387

BCLllA-13613 - UACAGUAAGUAUUUUCUUUCA 21 3' 14388

BCLllA-13614 - GUACAGUAAGUAUUUUCUUUCA 22 3' 14389

BCLllA-13615 - AGUACAGUAAGUAUUUUCUUUCA 23 3' 14390

BCLllA-13616 - CAGUACAGUAAGUAUUUUCUUUCA 24 3' 14391

BCLllA-13617 - UUUCAUGUUAAGCAAAAC 18 3' 14392

BCLllA-13618 - UUUUCAUGUUAAGCAAAAC 19 3' 14393

BCLllA-13619 - AUUUUCAUGUUAAGCAAAAC 20 3' 14394

BCLllA-13620 - UAUUUUCAUGUUAAGCAAAAC 21 3' 14395

BCLllA-13621 - UUAUUUUCAUGUUAAGCAAAAC 22 3' 14396

BCLllA-13622 - AUUAUUUUCAUGU U AAGCAAAAC 23 3' 14397

BCLllA-13623 - UAUUAUUUUCAUGUUAAGCAAAAC 24 3' 14398

BCLllA-13624 - AGUAUUUUCUUUCAUUGG 18 3' 14399

BCLllA-13625 - AAGUAUUUUCUUUCAUUGG 19 3' 14400

BCLllA-13626 - UAAGUAUUUUCUUUCAUUGG 20 3' 14401

BCLllA-13627 - GUAAGUAUUUUCUUUCAUUGG 21 3' 14402

BCLllA-13628 - AGUAAGUAUUUUCUUUCAUUGG 22 3' 14403

BCLllA-13629 - CAGUAAGUAUUUUCUUUCAUUGG 23 3' 14404

BCLllA-13630 - ACAGUAAGUAUUUUCUUUCAUUGG 24 3' 14405

BCLllA-13631 - AAGUAUUUUCUUUCAUUG 18 3' 14406

BCLllA-13632 - UAAGUAUUUUCUUUCAUUG 19 3' 14407

BCLllA-13633 - GUAAGUAUUUUCUUUCAUUG 20 3' 14408

BCLllA-13634 - AGUAAGUAUUUUCUUUCAUUG 21 3' 14409

BCLllA-13635 - CAGUAAGUAUUUUCUUUCAUUG 22 3' 14410

BCLllA-13636 - ACAGUAAGUAUUUUCUUUCAUUG 23 3' 14411 BCLllA-13637 - UACAGUAAGUAUUUUCUUUCAUUG 24 3' 14412

BCLllA-13638 - GUAAGUAUUUUCUU UCAU 18 3' 14413

BCLllA-13639 - AGUAAGUAUUUUCUUUCAU 19 3' 14414

BCLllA-13640 - CAGUAAGUAUUUUCUU UCAU 20 3' 14415

BCLllA-13641 - ACAGUAAGUAUUUUCUUUCAU 21 3' 14416

BCLllA-13642 - UACAGUAAGUAUUUUCUUUCAU 22 3' 14417

BCLllA-13643 - GUACAGUAAGUAUUUUCUUUCAU 23 3' 14418

BCLllA-13644 - AGUACAGUAAGUAUUU UCUUUCAU 24 3' 14419

BCLllA-13645 - UUGGCUAUUGAUACUGAU 18 3' 14420

BCLllA-13646 - UUUGGCUAUUGAUACUGAU 19 3' 14421

BCLllA-13647 - CUU UGGCUAUUGAUACUGAU 20 3' 14422

BCLllA-13648 - UCUUUGGCUAUUGAUACUGAU 21 3' 14423

BCLllA-13649 - AUCUUUGGCUAUUGAUACUGAU 22 3' 14424

BCLllA-13650 - GAUCUUUGGCUAUUGAUACUGAU 23 3' 14425

BCLllA-13651 - GGAUCUUUGGCUAUUGAUACUGAU 24 3' 14426

BCLllA-13652 - UAAGUAUUUUCUUUCAUU 18 3' 14427

BCLllA-13653 - GUAAGUAUUUUCUU UCAUU 19 3' 14428

BCLllA-13654 - AGUAAGUAUUUUCUUUCAUU 20 3' 14429

BCLllA-13655 - CAGUAAGUAUUUUCUU UCAUU 21 3' 14430

BCLllA-13656 - ACAGUAAGUAUUUUCUUUCAUU 22 3' 14431

BCLllA-13657 - UACAGUAAGUAUUUUCUUUCAUU 23 3' 14432

BCLllA-13658 - GUACAGUAAGUAUUUUCUUUCAUU 24 3' 14433

Table 20A provides exemplary targeting domains for removing (e.g., deleting) the enhancer region the BCLl 1A gene selected according to the first tier parameters. The targeting domains bind within a region 5' (51.5 to 51.7kb downstream of TSS) or 3' (65.1 to 65.3kb downstream of TSS), have a high level of orthogonality, and start with 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 20A

Table 20B provides exemplary targeting domains for removing (e.g., deleting) the enhancer region the BCLl 1A gene selected according to the second tier parameters. The targeting domains bind within a region 5' (51.5 to 51.7kb downstream of TSS) or 3' (65.1 to 65.3kb downstream of 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 N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 20B

Table 20C provides exemplary targeting domains for removing (e.g., deleting) the enhancer region the BCLl 1A gene selected according to the fourth tier parameters. The targeting domains bind within a region 5' (51.5 to 51.7kb downstream of TSS) or 3' (65.1 to 65.3kb downstream of 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. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single- stranded break (Cas9 nickase).

Table 20C

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, Neisseria flavescens, Neisseria lactamica, Neisseria sp., Neisseria wadsworthii, Nitrosomonas sp., Parvibaculum lavamentivorans, Pasteur ella 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 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 in an embodiment, a 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 21.

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 comprise 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 RECl 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 RECl 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 RECl domain comprises two RECl motifs at amino acids 94 to 179 and 308 to 717 of the sequence of S. pyogenes Cas9. These two RECl domains, though separated by the REC2 domain in the linear primary structure, assemble in the tertiary structure to form the RECl 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, the HNH 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. 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.

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);

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

X3 is selected from N, S, G, A, D, T, R, M and F (e.g., A or N);

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.

D-I-G-T-N-S-V-G-W-A-V-X (SEQ ID NO: 11),

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 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:

X 1 -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

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:

X 1 -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),

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.

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);

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;

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 eaCas9 molecule or Cas9 polypeptide comprises one or more of the following enzymatic 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 or an eaCas9 molecule or 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 domain. In an embodiment, an eaCas9 molecule or eaCas9 polypeptide comprises cleavage activity associated with a RuvC domain. In an embodiment, an eaCas9 molecule or eaCas9 polypeptide comprises cleavage activity associated with an HNH domain and cleavage activity associated with a RuvC domain. In an embodiment, an eaCas9 molecule or eaCas9 polypeptide comprises an active, or cleavage competent, HNH domain and an inactive, or cleavage incompetent, RuvC domain. In an embodiment, an eaCas9 molecule or eaCas9 polypeptide comprises an inactive, or cleavage incompetent, HNH domain and an active, or cleavage competent, RuvC 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 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 in an embodiment, a 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 ah, SCIENCE 2013; 339(6121): 823-826. In an embodiment, an eaCas9 molecule of S. thermophilus recognizes the sequence motif NGGNG (SEQ ID NO.: 90) and/or NNAGAAW (W = A or T) (SEQ ID NO.: 91) and directs cleavage of a 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) (SEQ ID NO.: 92) and directs cleavage of a 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) (SEQ ID NO.: 93) 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) (SEQ ID NO.: ) 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 N. meningitidis recognizes the sequence motif NNNNGATT or NNNGCTT (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. See, e.g., Hou et al, PNAS 2013; 110(39): 15644-15649. 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 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. equities (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 meningitidis (Hou et al., 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 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 of S. pyogenes, S. thermophilus, S. mutans and L. innocua, and "-" indicates any amino acid. In an embodiment, a Cas9 molecule or Cas9 polypeptide differs from the sequence of the consensus sequence disclosed in 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 of S. pyogenes, or N. meningitidis, "-" 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 amino acids 1-180 (the numbering is according to the motif sequence in Fig. 2; 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 1 ' :

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 Fig. 2 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 Fig. 2 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.

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 Fig. 2 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 or Cas9 polypeptide, e.g., an eaCas9 molecule or eaCas9 polypeptide, 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

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: 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 a typical embodiment, a Cas9 molecule or Cas9 polypeptide has 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 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.

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 . 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 domains, e.g., an N-terminal RuvC domain; an HNH domain; a region outside the RuvC domains and the HNH domain. In an embodiment, a mutation(s) is present in a RuvC domain. In an embodiment, a mutation(s) is present in an HNH domain. In an embodiment, mutations are present in both a RuvC domain and an HNH 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 is an eiCas9 molecule 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 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. 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 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 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 is an eaCas9 molecule 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 is an eiCas9 molecule 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 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.

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 In an embodiment, the altered Cas9 molecule or Cas9 polypeptide comprises a sequence in which:

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 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.

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.

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 Cas9 molecule of a species other than S. pyogenes (e.g., S. thermophilus) comprising an HNH-like domain. Cas9 Molecules and 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, e.g., S. pyogenes, S. thermophilus, 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 an 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 can be altered, e.g., to alter PAM recognition, e.g., to alter the PAM sequence that the Cas9 molecule or Cas9 polypeptide 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 poypeptide 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 Syn-Cas9 polypetide comprises:

a) a Cas9 core domain, e.g., a Cas9 core domain from Table 21 or 22, 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 24 and 25. 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 21 and said altered PI domain comprises a PI domain from a species Y Cas9 from Table 21.

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 21. 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 21.

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 25.

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 25.

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 25.

In an embodiment, the Cas9 molecule 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 24 and 25. The sequences for the 83 Cas9 orthologs referenced in Tables 24 and 25 are provided in Table 21. Table 23 provides the Cas9 orthologs with known PAM sequences and the corresponding RKR motif.

In an embodiment, a Syn-Cas9 molecule may also be size- optimized, e.g., the Syn-Cas9 molecule 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 comprises a REC deletion.

Size-Optimized Cas9 Molecules

Engineered Cas9 molecules and engineered Cas9 polypeptides described herein include 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 delivery methods, and thereby increases utility for genome-editing. A Cas9 molecule can comprise one or more deletions that do not substantially affect or decrease the activity of the resultant Cas9 molecules described herein. Activities that are retained in the Cas9 molecules 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 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 21, 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

A REC-optimized Cas9 molecule, as that term is used herein, refers to a Cas9 molecule that comprises a deletion in one or both of the REC2 domain and the RE1_CT domain (collectively a REC deletion), wherein the deletion comprises at least 10% of the amino acid residues in the cognate domain. A REC-optimized Cas9 molecule can be an eaCas9 molecule or an eiCas9 molecule. An exemplary REC-optimizedCas9 molecule comprises:

a) a deletion selected from:

i) a REC2 deletion;

ii) a REC IC_T deletion; or

iii) a REC 1 _SUB deletion.

Optionally, a linker is disposed between the amino acid residues that flank the deletion. In an embodiment a Cas9 molecule includes only one deletion, or only two deletions. A Cas9 molecule can comprise a REC2 deletion and a REC I_CT deletion. A Cas9 molecule can comprise a REC2 deletion and a REC 1 _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 can include a linker disposed between the amino acid residues that flank the deletion. Suitable linkers for use between the amino acid resides that flank a REC deletion in a REC-optimized Cas9 molecule is disclosed in Section V.

In an embodiment a REC-optimized Cas9 molecule 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 21, 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 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 21, 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 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 21, 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 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 21.

The amino acid sequences of exemplary Cas9 molecules from different bacterial species are shown below.

Table 21. Amino Acid Sequence of Cas9 Orthologs

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

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

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 1 16627542lref 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 1 150502.1 356

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

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

1 1 170 366

gil83591793 Irefl YP_425545.11

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_00141 1379

.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

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 gill l7929158lreflYP_873709.1 l 385

Mycoplasma ovipneumoniae SEQ ID NO: 156 184 29 381 420 62 381 420 62

SCOl 386

gil363542550lreflZP_09312133.1

Table 22. Amino Acid Sequence of Cas9 Core Domains

Table 23. Identified PAM sequences and corresponding RKR motifs.

PI domains are provided in Tables 24 and 25.

Table 24. Altered PI Domains

Table 25. Other Altered PI Domains

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 DJO10A 904 1187 284 VRK

Amino acid sequences described in Table 21:

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 MPQV IVKKTEVQTGGFSKES 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 VLKQALVNITFNCFDTNSAI SS I SNILMESGKTKSDKAKAIERLVDTYTVFDEVNTPDKPQKEQ VKEDKKTLKAFANLVLGLSANLIDLFGSVEDIDDDLKKLQIVGDTYDEKRDELAKVWGDEIHI I DDCKSVYDAI ILMS IKEPGLTI SQSKVKAFDKHKEDLVILKSLLKLDRNVYNEMFKSDKKGLHN YVHYIKQGRTEETSCSREDFYKYTKKIVEGLADSKDKEYILNEIELQTLLPLQRIKDNGVIPYQ LHLEELKVILDKCGPKFPFLHTVSDGFSVTEKLIKMLEFRIPYYVGPLNTHHNIDNGGFSWAVR KQAGRVTPWNFEEKIDREKSAAAFIKNLTNKCTYLFGEDVLPKSSLLYSEFMLLNELNNVRIDG KALAQGVKQHLIDSIFKQDHKKMTKNRIELFLKDNNYITKKHKPEITGLDGEIKNDLTSYRDMV RILGNNFDVSMAEDI ITDITIFGESKKMLRQTLRNKFGSQLNDETIKKLSKLRYRDWGRLSKKL LKGIDGCDKAGNGAPKTI IELMRNDSYNLMEILGDKFSFMECIEEENAKLAQGQVVNPHDI IDE LALSPAVKRAVWQALRIVDEVAHIKKALPSRIFVEVARTNKSEKKKKDSRQKRLSDLYSAIKKD DVLQSGLQDKEFGALKSGLANYDDAALRSKKLYLYYTQMGRCAYTGNI IDLNQLNTDNYDIDHI YPRSLTKDDSFDNLVLCERTANAKKSDIYPIDNRIQTKQKPFWAFLKHQGLI 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 SSVTIKQVADNLVAHGDFARRPEIRGLADEKRFLSSLSTYHQLKEILHEAIDDPTKLLDIENII 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 I SEAMVSRYNKHHDDLKLLKDCIKNNVPNKYFDMFRNDSEKSKGYYNYINRPSKAPVDEFYKYV KKCIEKVDTPEAKQILNDIELENFLLKQNSRTNGSVPYQMQLDEMIKI IDNQAEYYPILKEKRE QLLS ILTFRIPYYFGPLNETSEHAWIKRLEGKENQRILPWNYQDIVDVDATAEGFIKRMRSYCT YFPDEEVLPKNSLIVSKYEVYNELNKIRVDDKLLEVDVKNDIYNELFMKNKTVTEKKLKNWLVN NQCCSKDAEIKGFQKENQFSTSLTPWIDFTNIFGKIDQSNFDLIENI IYDLTVFEDKKIMKRRL KKKYALPDDKVKQILKLKYKDWSRLSKKLLDGIVADNRFGSSVTVLDVLEMSRLNLMEI INDKD LGYAQMIEEATSCPEDGKFTYEEVERLAGSPALKRGIWQSLQIVEEITKVMKCRPKYIYIEFER SEEAKERTESKIKKLENVYKDLDEQTKKEYKSVLEELKGFDNTKKI SSDSLFLYFTQLGKCMYS GKKLDIDSLDKYQIDHIVPQSLVKDDSFDNRVLVVPSENQRKLDDLVVPFDIRDKMYRFWKLLF DHELI SPKKFYSLIKTEYTERDEERFINRQLVETRQITKNVTQI IEDHYSTTKVAAIRANLSHE FRVKNHIYKNRDINDYHHAHDAYIVALIGGFMRDRYPNMHDSKAVYSEYMKMFRKNKNDQKRWK DGFVINSMNYPYEVDGKLIWNPDLINEIKKCFYYKDCYCTTKLDQKSGQLFNLTVLSNDAHADK GVTKAVVPVNKNRSDVHKYGGFSGLQYTIVAIEGQKKKGKKTELVKKI SGVPLHLKAAS INEKI NYIEEKEGLSDVRI IKDNIPVNQMIEMDGGEYLLTSPTEYVNARQLVLNEKQCALIADIYNAIY KQDYDNLDDILMIQLYIELTNKMKVLYPAYRGIAEKFESMNENYVVI SKEEKANI 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 ITKETIVGVKEIKFGRNKVEKADKTPKKPNLQAYRPIKTSDERLC ILRYGGRTS 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 ELNDYHHAHDAYLAVVVGQTLLKVYPKLAPELIYGHHAHFNRHEENKATLRKHLYS IMRFFNN 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 KLISQRKFDNLTKAERGGLSPEDKAGFIQRQLVETRQITKHVARLLDEKFNNKKDENNRAVRTV 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 EKYQFKQ IENYKAENYDEKQNLHEELDDMYI 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 ELQNKKEITFSAIFKKLKAEFDLREGIDFLNGMSPKDKLKGNETKLQLQKSLGELWDVLGLDSI 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 GEEEETPNKLVEYYSLKVEKVEDSGERKGKDTWYNVHLENGMIYRRTS IPLDWEGKTKEFIVT TDLEADGSPKKDKEG IKRSFRAPKDDDWTLIKKKTEADIDKIKMTVGAYIYDTLLQKPDQKIR 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 ETSVADDKNTSGRIPKFHRVQSLKAYEERNIRKVRVDLLGRI SLL 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 QAFYPNELTDDWIALFVQPGIAEEAGLIYRKRPYYHGPGNEANNSPYGRWSDFQKTGEPATNIF DKLIGKDFQGELRASGLSLSAQQYNLLNDLTNLKIDGEVPLSSEQKEYILTELMTKEFTRFGVN DVVKLLGVKKERLSGWRLDKKGKPEIHTLKGYRNWRKIFAEAGIDLATLPTETIDCLAKVLTLN TEREGIENTLAFELPELSESVKLLVLDRYKELSQS I STQSWHRFSLKTLHLLIPELMNATSEQN TLLEQFQLKSDVRKRYSEYKKLPTKDVLAEIYNPTVNKTVSQAFKVIDALLVKYGKEQIRYITI EMPRDDNEEDEKKRIKELHAKNSQRKNDSQSYFMQKSGWSQEKFQTTIQKNRRFLAKLLYYYEQ DGICAYTGLPI SPELLVSDSTEIDHI IPI S I SLDDS INNKVLVLSKANQVKGQQTPYDAWMDGS FKKINGKFSNWDDYQKWVESRHFSHKKENNLLETRNIFDSEQVEKFLARNLNDTRYASRLVLNT LQSFFTNQETKVRVVNGSFTHTLRKKWGADLDKTRETHHHHAVDATLCAVTSFVKVSRYHYAVK EETGEKVMREIDFETGEIVNEMSYWEFKKSKKYERKTYQVKWPNFREQLKPVNLHPRIKFSHQV DRKANRKLSDATIYSVREKTEVKTLKSGKQKITTDEYTIGKIKDIYTLDGWEAFKKKQDKLLMK DLDEKTYERLLS IAETTPDFQEVEEKNGKVKRVKRSPFAVYCEENDIPAIQKYAKKNNGPLIRS LKYYDGKLNKHINITKDSQGRPVEKTKNGRKVTLQSLKPYRYDIYQDLETKAYYTVQLYYSDLR FVEGKYGITEKEYMKKVAEQTKGQVVRFCFSLQKNDGLEIEWKDSQRYDVRFYNFQSANS INFK GLEQEMMPAENQFKQKPYNNGAINLNIAKYGKEGKKLRKFNTDILGKKHYLFYEKEPKNI IK

SEQ ID NO: 352

MYFYKNKENKLNKKVVLGLDLGIASVGWCLTDI SQKEDNKFPI ILHGVRLFETVDDSDDKLLNE TRRKKRGQRRRNRRLFTRKRDFIKYLIDNNI IELEFDKNPKILVRNFIEKYINPFSKNLELKYK SVTNLPIGFHNLRKAAINEKYKLDKSELIVLLYFYLSLRGAFFDNPEDTKSKEMNKNEIEIFDK NES IKNAEFPIDKI IEFYKI SGKIRSTINLKFGHQDYLKEIKQVFEKQNIDFMNYEKFAMEEKS FFSRIRNYSEGPGNEKSFSKYGLYANENGNPELI INEKGQKIYTKIFKTLWESKIGKCSYDKKL YRAPKNSFSAKVFDITNKLTDWKHKNEYI SERLKRKILLSRFLNKDSKSAVEKILKEE IKFEN 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 SRAAGQGEAAGQSAEL IARDTPPPWEGFRDDLRVRLDRI 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 IKYPNI IELKTKALSQEVCPDEIAWILHDYLKNRG YFYDEKETKEDFDQQTVESMPSYKLNEFYKKYGYFKGALSQPTESEMKDNKDLKEAFFFDFSNK EWLKEINYFFNVQKNILSETFIEEFKKIFSFTRDI SKGPGSDNMPSPYGIFGEFGDNGQGGRYE HIWDKNIGKCS IFTNEQRAPKYLPSALIFNFLNELANIRLYSTDKKNIQPLWKLSSVDKLNILL NLFNLPI SEKKKKLTSTNINDIVKKES IKS IMI SVEDIDMIKDEWAGKEPNVYGVGLSGLNIEE SAKENKFKFQDLKILNVLINLLDNVGIKFEFKDRNDI IKNLELLDNLYLFLIYQKESNNKDSS I DLFIAKNESLNIENLKLKLKEFLLGAGNEFENHNSKTHSLSKKAIDEILPKLLDNNEGWNLEAI KNYDEEIKSQIEDNSSLMAKQDKKYLNDNFLKDAILPPNVKVTFQQAILIFNKI IQKFSKDFEI DKVVIELAREMTQDQENDALKGIAKAQKSKKSLVEERLEANNIDKSVFNDKYEKLIYKIFLWI S QDFKDPYTGAQI SVNEIVNNKVEIDHI IPYSLCFDDSSANKVLVHKQSNQEKSNSLPYEYIKQG HSGWNWDEFTKYVKRVFVNNVDS ILSKKERLKKSENLLTASYDGYDKLGFLARNLNDTRYATIL FRDQLNNYAEHHLIDNKKMFKVIAMNGAVTSFIRKNMSYDNKLRLKDRSDFSHHAYDAAI IALF 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 PYAGDQIKKMVGKDIFEPTEDRAAKATYTFQYFNLLQKMTSLNYQNTTGDTWHTLNGLDRQAII 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 RIG I 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 SFFTEIYKKCAAKHS ILEVKVKALDS 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 IGNKNPQIANLLTLADNKTDKKFLLHDENYKE IETGELVKIPKFEVDKLAKV 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 polypeptides are provided herein.

Exemplary nucleic acids encoding Cas9 molecules or Cas9 polypeptides are described in Cong et al., 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. ATGGCCGCCT TCAAGCCCAACCCCATCAACTACATCCTGGGCCTGGACATCGGCATCGCCAGCG TGGGCTGGGCCATGGTGGAGATCGACGAGGACGAGAACCCCATCTGCCTGATCGACCTGGGTGT GCGCGTGT TCGAGCGCGCTGAGGTGCCCAAGACTGGTGACAGTCTGGCTATGGCTCGCCGGCT T GCTCGCTCTGT TCGGCGCCT TACTCGCCGGCGCGCTCACCGCCT TCTGCGCGCTCGCCGCCTGC TGAAGCGCGAGGGTGTGCTGCAGGCTGCCGACT TCGACGAGAACGGCCTGATCAAGAGCCTGCC CAACACTCCT TGGCAGCTGCGCGCTGCCGCTCTGGACCGCAAGCTGACTCCTCTGGAGTGGAGC GCCGTGCTGCTGCACCTGATCAAGCACCGCGGCTACCTGAGCCAGCGCAAGAACGAGGGCGAGA CCGCCGACAAGGAGCTGGGTGCTCTGCTGAAGGGCGTGGCCGACAACGCCCACGCCCTGCAGAC TGGTGACT TCCGCACTCCTGCTGAGCTGGCCCTGAACAAGT TCGAGAAGGAGAGCGGCCACATC CGCAACCAGCGCGGCGACTACAGCCACACCT TCAGCCGCAAGGACCTGCAGGCCGAGCTGATCC TGCTGT TCGAGAAGCAGAAGGAGT TCGGCAACCCCCACGTGAGCGGCGGCCTGAAGGAGGGCAT CGAGACCCTGCTGATGACCCAGCGCCCCGCCCTGAGCGGCGACGCCGTGCAGAAGATGCTGGGC CACTGCACCT TCGAGCCAGCCGAGCCCAAGGCCGCCAAGAACACCTACACCGCCGAGCGCT TCA TCTGGCTGACCAAGCTGAACAACCTGCGCATCCTGGAGCAGGGCAGCGAGCGCCCCCTGACCGA CACCGAGCGCGCCACCCTGATGGACGAGCCCTACCGCAAGAGCAAGCTGACCTACGCCCAGGCC CGCAAGCTGCTGGGTCTGGAGGACACCGCCT TCT TCAAGGGCCTGCGCTACGGCAAGGACAACG CCGAGGCCAGCACCCTGATGGAGATGAAGGCCTACCACGCCATCAGCCGCGCCCTGGAGAAGGA GGGCCTGAAGGACAAGAAGAGTCCTCTGAACCTGAGCCCCGAGCTGCAGGACGAGATCGGCACC GCCT TCAGCCTGT TCAAGACCGACGAGGACATCACCGGCCGCCTGAAGGACCGCATCCAGCCCG AGATCCTGGAGGCCCTGCTGAAGCACATCAGCT TCGACAAGT TCGTGCAGATCAGCCTGAAGGC CCTGCGCCGCATCGTGCCCCTGATGGAGCAGGGCAAGCGCTACGACGAGGCCTGCGCCGAGATC TACGGCGACCACTACGGCAAGAAGAACACCGAGGAGAAGATCTACCTGCCTCCTATCCCCGCCG ACGAGATCCGCAACCCCGTGGTGCTGCGCGCCCTGAGCCAGGCCCGCAAGGTGATCAACGGCGT GGTGCGCCGCTACGGCAGCCCCGCCCGCATCCACATCGAGACCGCCCGCGAGGTGGGCAAGAGC T TCAAGGACCGCAAGGAGATCGAGAAGCGCCAGGAGGAGAACCGCAAGGACCGCGAGAAGGCCG CCGCCAAGT TCCGCGAGTACT TCCCCAACT TCGTGGGCGAGCCCAAGAGCAAGGACATCCTGAA GCTGCGCCTGTACGAGCAGCAGCACGGCAAGTGCCTGTACAGCGGCAAGGAGATCAACCTGGGC CGCCTGAACGAGAAGGGCTACGTGGAGATCGACCACGCCCTGCCCT TCAGCCGCACCTGGGACG ACAGCT TCAACAACAAGGTGCTGGTGCTGGGCAGCGAGAACCAGAACAAGGGCAACCAGACCCC CTACGAGTACT TCAACGGCAAGGACAACAGCCGCGAGTGGCAGGAGT TCAAGGCCCGCGTGGAG ACCAGCCGCT TCCCCCGCAGCAAGAAGCAGCGCATCCTGCTGCAGAAGT TCGACGAGGACGGCT TCAAGGAGCGCAACCTGAACGACACCCGCTACGTGAACCGCT TCCTGTGCCAGT TCGTGGCCGA CCGCATGCGCCTGACCGGCAAGGGCAAGAAGCGCGTGT TCGCCAGCAACGGCCAGATCACCAAC CTGCTGCGCGGCT TCTGGGGCCTGCGCAAGGTGCGCGCCGAGAACGACCGCCACCACGCCCTGG ACGCCGTGGTGGTGGCCTGCAGCACCGTGGCCATGCAGCAGAAGATCACCCGCT TCGTGCGCTA CAAGGAGATGAACGCCT TCGACGGTAAAACCATCGACAAGGAGACCGGCGAGGTGCTGCACCAG AAGACCCACT TCCCCCAGCCCTGGGAGT TCT TCGCCCAGGAGGTGATGATCCGCGTGT TCGGCA AGCCCGACGGCAAGCCCGAGT TCGAGGAGGCCGACACCCCCGAGAAGCTGCGCACCCTGCTGGC CGAGAAGCTGAGCAGCCGCCCTGAGGCCGTGCACGAGTACGTGACTCCTCTGT TCGTGAGCCGC GCCCCCAACCGCAAGATGAGCGGTCAGGGTCACATGGAGACCGTGAAGAGCGCCAAGCGCCTGG ACGAGGGCGTGAGCGTGCTGCGCGTGCCCCTGACCCAGCTGAAGCTGAAGGACCTGGAGAAGAT GGTGAACCGCGAGCGCGAGCCCAAGCTGTACGAGGCCCTGAAGGCCCGCCTGGAGGCCCACAAG GACGACCCCGCCAAGGCCT TCGCCGAGCCCT TCTACAAGTACGACAAGGCCGGCAACCGCACCC AGCAGGTGAAGGCCGTGCGCGTGGAGCAGGTGCAGAAGACCGGCGTGTGGGTGCGCAACCACAA CGGCATCGCCGACAACGCCACCATGGTGCGCGTGGACGTGT TCGAGAAGGGCGACAAGTACTAC CTGGTGCCCATCTACAGCTGGCAGGTGGCCAAGGGCATCCTGCCCGACCGCGCCGTGGTGCAGG GCAAGGACGAGGAGGACTGGCAGCTGATCGACGACAGCT TCAACT TCAAGT TCAGCCTGCACCC 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 IANADFIFKEWKKLDKAKKVMENQMFEEKQAESMPEIETEQEYKEIFITPHQIKHIKDFKD YKYSHRVDKKPNRELINDTLYSTRKDDKGNTLIVNNLNGLYDKDNDKLKKLINKSPEKLLMYHH DPQTYQKLKLIMEQYGDEKNPLYKYYEETGNYLTKYSKKDNGPVIKKIKYYGNKLNAHLDITDD YPNSRNKVVKLSLKPYRFDVYLDNGVYKFVTVKNLDVIKKENYYEVNSKCYEEAKKLKKI SNQA 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 Cas Polypeptides

Various types of Cas molecules or Cas 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 26.

Table 26: 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

cas4 • Subtype I-A cas4 and csal NA COG1468 APE1239 and BH0340

• Subtype I-B

• Subtype I-C

• Subtype I-D

• Subtype II- B

cas5 • Subtype I-A cas5a, cas5d, 3KG4 COG1688 APE1234, BH0337,

• Subtype I-B cas5e, cas5h, (RAMP) devS and ygcl

• Subtype I-C cas5p, cas5t

• Subtype I-E and cmx5

cas6 • Subtype I-A cas6 and cmx6 3I4H COG1583 and PF1131 and slr7014

• Subtype I-B COG5551

• Subtype I-D (RAMP)

• Subtype III- Α· Subtype

III-B

cas6e • Subtype I-E cse3 1WJ9 (RAMP) ygcH

cas6f • Subtype I-F csy4 2XLJ (RAMP) yl727

cas7 • Subtype I-A csal, csd2, NA COG 1857 and devR and ygcJ

• 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 cspl 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) y!725 Table 26: 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

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

csm.2 • Subtype III- csm.2 NA COG1421 MTH1081 and

A« SERP2460 csm.3 • Subtype III- csc2 and csm.3 NA COG1337 MTH1080 and

A (RAMP) SERP2459 csm.4 • Subtype III- csm4 NA COG 1567 MTH1079 and

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 csm6 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 csb2 • 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 Table 26: Cas Systems

(PDB encoded

accessions)¹ protein

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 μΐ_^ 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

phosphorimaging.

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

Described herein are methods for (1) targeted knockout of one or both alleles of the

BCL11A gene using NHEJ and (2) NHEJ-mediated removal of an enhancer region in the BCL11A gene (see Section V.l). In another embodiment, methods are provided for targeted knockdown of the BCL11A gene (see Section V.2).

V.l 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) sequences 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 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 (e.g., motifs less than or equal to 50 nucleotides in length) as long as the generation of a specific final sequence is not required. If a double- strand break is targeted near to a 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. In this way, DNA segments as large as several hundred kilobases can be deleted. 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 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 start codon, within a first exon of the coding sequence, or within 500 bp of the start codon (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 strand 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 strand 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.2 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.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, ERCCl, XPA-G, and

LIGl. Transcription-coupled NER (TC-NER) can involve the following factors: CSA, CSB, XPB, XPD, XPG, ERCCl, and TTDA. Additional factors that may promote the NER repair pathway include XPA-G, POLH, XPF, ERCCl, XPA-G, LIGl, 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 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., 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, 200, 250, 300, 350, 400, 450, or 500 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 16 nucleotides, e.g., a targeting domain of (i) 16, (ii), 17, (iii) 18, (iv) 19, (v) 20, (vi) 21, (vii) 22, (viii) 23, (ix) 24, (x) 25, or (xi) 26 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.

Jl an embodiment, the gRNA is configured such that it comprises properties: a and b(i).

Jl an embodiment, the gRNA is configured such that it comprises properties: a and b(ii).

Jl an embodiment, the gRNA is configured such that it comprises properties: a and b(iii).

11 an embodiment, the gRNA is configured such that it comprises properties: a and b(iv).

11 an embodiment, the gRNA is configured such that it comprises properties: a and b(v).

11 an embodiment, the gRNA is configured such that it comprises properties: a and b(vi).

11 an embodiment, the gRNA is configured such that it comprises properties: a and b(vii).

11 an embodiment, the gRNA is configured such that it comprises properties: a and b(viii).

11 an embodiment, the gRNA is configured such that it comprises properties: a and b(ix).

11 an embodiment, the gRNA is configured such that it comprises properties: a and b(x).

11 an embodiment, the gRNA is configured such that it comprises properties: a and b(xi).

11 an embodiment, the gRNA is configured such that it comprises properties: a and c.

11 an embodiment, the gRNA is configured such that in comprises properties: a, b, and c.

11 an embodiment, the gRNA is configured such that in comprises properties: a(i), b(i), and c(i)

11 an embodiment, the gRNA is configured such that in comprises properties: a(i), b(i), and c(ii

11 an embodiment, the gRNA is configured such that in comprises properties: a(i), b(ii), and c(i)

[n an embodiment, the gRNA is configured such that in comprises properties: a(i), b(ii), and c(ii). In an embodiment, the gRNA is configured such that in comprises properties: a(i), b(iii), n an embodiment, the gRNA is configured such that in comprises properties: a(i), b(iii), n an embodiment, the gRNA is configured such that in comprises properties: a(i), b(iv), n an embodiment, the gRNA is configured such that in comprises properties: a(i), b(iv), n an embodiment, the gRNA is configured such that in comprises properties: a(i), b(v), n an embodiment, the gRNA is configured such that in comprises properties: a(i), b(v), n an embodiment, the gRNA is configured such that in comprises properties: a(i), b(vi), n an embodiment, the gRNA is configured such that in comprises properties: a(i), b(vi), n an embodiment, the gRNA is configured such that in comprises properties: a(i), b(vii), n an embodiment, the gRNA is configured such that in comprises properties: a(i), b(vii), n an embodiment, the gRNA is configured such that in comprises properties: a(i), b(viii), n an embodiment, the gRNA is configured such that in comprises properties: a(i), b(viii), n an embodiment, the gRNA is configured such that in comprises properties: a(i), b(ix), n an embodiment, the gRNA is configured such that in comprises properties: a(i), b(ix), n an embodiment, the gRNA is configured such that in comprises properties: a(i), b(x), In an embodiment, the gRNA is configured such that in comprises properties: a(i), b(x), and c(ii).

In an embodiment, the gRNA is configured such that in comprises properties: a(i), b(xi), and c(i).

In an embodiment, the gRNA is configured such that in comprises properties: a(i), b(xi), and c(ii).

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, 200, 250, 300, 350, 400, 450, or 500 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 16 nucleotides, e.g., a targeting domain of (i) 16, (ii), 17, (iii) 18, (iv) 19, (v) 20, (vi) 21, (vii) 22, (viii) 23, (ix) 24, (x) 25, or (xi) 26 nucleotides; and

c)

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

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 b(iv).

In an embodiment, the gRNA is configured such that it comprises properties: a and b(v).

In an embodiment, the gRNA is configured such that it comprises properties: a and b(vi).

In an embodiment, the gRNA is configured such that it comprises properties: a and b(vii).

In an embodiment, the gRNA is configured such that it comprises properties: a and b(viii)

In an embodiment, the gRNA is configured such that it comprises properties: a and b(ix).

In an embodiment, the gRNA is configured such that it comprises properties: a and b(x).

In an embodiment, the gRNA is configured such that it comprises properties: a and b(xi).

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(ii), n an embodiment, the gRNA is configured such that in comprises properties: a(i), b(ii), n an embodiment, the gRNA is configured such that in comprises properties: a(i), b(iii), n an embodiment, the gRNA is configured such that in comprises properties: a(i), b(iii), n an embodiment, the gRNA is configured such that in comprises properties: a(i), b(iv), n an embodiment, the gRNA is configured such that in comprises properties: a(i), b(iv), n an embodiment, the gRNA is configured such that in comprises properties: a(i), b(v), n an embodiment, the gRNA is configured such that in comprises properties: a(i), b(v), n an embodiment, the gRNA is configured such that in comprises properties: a(i), b(vi), n an embodiment, the gRNA is configured such that in comprises properties: a(i), b(vi), n an embodiment, the gRNA is configured such that in comprises properties: a(i), b(vii), n an embodiment, the gRNA is configured such that in comprises properties: a(i), b(vii), n an embodiment, the gRNA is configured such that in comprises properties: a(i), b(viii), n an embodiment, the gRNA is configured such that in comprises properties: a(i), b(viii), n an embodiment, the gRNA is configured such that in comprises properties: a(i), b(ix), In an embodiment, the gRNA is configured such that in comprises properties: a(i), b(ix), and c(ii).

In an embodiment, the gRNA is configured such that in comprises properties: a(i), b(x), and c(i).

In an embodiment, the gRNA is configured such that in comprises properties: a(i), b(x), 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, 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;

b) one or both have a targeting domain of at least 16 nucleotides, e.g., a targeting domain of (i) 16, (ii), 17, (iii) 18, (iv) 19, (v) 20, (vi) 21, (vii) 22, (viii) 23, (ix) 24, (x) 25, or (xi) 26 nucleotides;

c) for one or both:

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 is configured such that it comprises properties: a and b(iv).

In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a and b(v).

In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a and b(vi).

In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a and b(vii).

In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a and b(viii).

In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a and b(ix).

In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a and b(x).

In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a and b(xi).

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 it comprises properties: a, b, and c.

In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a(i), b(i), and c(i).

In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a(i), b(i), and c(ii).

In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a(i), b(i), c, and d.

In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a(i), b(i), c, and e. In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a(i), b(i), c, d, and e.

In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a(i), b(ii), and c(i).

In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a(i), b(ii), and c(ii).

In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a(i), b(ii), c, and d.

In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a(i), b(ii), c, and e.

In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a(i), b(ii), c, d, and e.

In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a(i), b(iii), and c(i).

In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a(i), b(iii), and c(ii).

In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a(i), b(iii), c, and d.

In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a(i), b(iii), c, and e.

In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a(i), b(iii), c, d, and e.

In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a(i), b(iv), and c(i).

In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a(i), b(iv), and c(ii).

In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a(i), b(iv), c, and d.

In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a(i), b(iv), c, and e. In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a(i), b(iv), c, d, and e.

In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a(i), b(v), and c(i).

In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a(i), b(v), and c(ii).

In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a(i), b(v), c, and d.

In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a(i), b(v), c, and e.

In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a(i), b(v), c, d, and e.

In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a(i), b(vi), and c(i).

In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a(i), b(vi), and c(ii).

In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a(i), b(vi), c, and d.

In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a(i), b(vi), c, and e.

In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a(i), b(vi), c, d, and e.

In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a(i), b(vii), and c(i).

In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a(i), b(vii), and c(ii).

In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a(i), b(vii), c, and d.

In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a(i), b(vii), c, and e. In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a(i), b(vii), c, d, and e.

In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a(i), b(viii), and c(i).

In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a(i), b(viii), and c(ii).

In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a(i), b(viii), c, and d.

In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a(i), b(viii), c, and e.

In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a(i), b(viii), c, d, and e.

In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a(i), b(ix), and c(i).

In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a(i), b(ix), and c(ii).

In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a(i), b(ix), c, and d.

In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a(i), b(ix), c, and e.

In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a(i), b(ix), c, d, and e.

In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a(i), b(x), and c(i).

In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a(i), b(x), and c(ii).

In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a(i), b(x), c, and d.

In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a(i), b(x), c, and e. In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a(i), b(x), c, d, and e.

In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a(i), b(xi), and c(i).

In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a(i), b(xi), and c(ii).

In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a(i), b(xi), c, and d.

In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a(i), b(xi), c, and e.

In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a(i), b(xi), 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 D10, 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., the H840A 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 N863, e.g., the N863A mutation.

VI. Target Cells

Cas9 molecules and gRNA molecules, e.g., a Cas9 molecule/gRNA molecule complex, 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., introducing a mutation in) the BCL11A target gene, e.g., as described herein. In an embodiment, the expression of the BCL11A target gene is modulated, e.g., in vivo. In another embodiment, the expression of the BCL11A target gene is modulated, e.g., ex vivo.

The Cas9 and gRNA molecules described herein can be delivered to a target cell. In an embodiment, the target cell is a circulating blood cell, e.g., a reticulocyte, a myeloid progenitor cell, or a hematopoietic stem cell. In an embodiment, the target cell is a bone marrow cell (e.g., a myeloid progenitor cell, an erythroid progenitor cell, a hematopoietic stem cell, or a mesenchymal stem cell). In an embodiment, the target cell is a myeloid progenitor cell (e.g., a common myeloid progenitor (CMP) cell). In an embodiment, the target cell is an erythroid progenitor cell (e.g., a megakaryocyte erythroid progenitor (MEP) cell). In an embodiment, the target cell is a hematopoietic stem cell (e.g., a long term hematopoietic stem cell (LT-HSC), a short term hematopoietic stem cell (ST-HSC), a multipotent progenitor (MPP) cell, a lineage restricted progenitor (LRP) cell).

In an embodiment, the target cell is manipulated ex vivo by editing (e.g., introducing a mutation in) the BCL11A target gene and/or modulating the expression of the BCL11A target gene, and administered to the subject. Sources of target cells for ex vivo manipulation may include, by way of example, the subject's blood, the subject's cord blood, or the subject's bone marrow. Sources of target cells for ex vivo manipulation may also include, by way of example, heterologous donor blood, cord blood, or bone marrow.

In an embodiment, a myeloid progenitor cell is removed from the subject, manipulated ex vivo as described above, and the myeloid progenitor cell is returned to the subject. In an embodiment, an erythroid progenitor cell is removed from the subject, manipulated ex vivo as described above, and the erythroid progenitor cell is returned to the subject. In an embodiment, a hematopoietic stem cell is removed from the subject, manipulated ex vivo as described above, and the hematopoietic stem cell is returned to the subject. In an embodiment, a CD34+ hematopoietic stem cell is removed from the subject, manipulated ex vivo as described above, and the CD34+ hematopoietic stem cell is returned to the subject.

A suitable cell can also include a stem cell such as, by way of example, an embryonic stem cell, an induced pluripotent stem cell, a hematopoietic stem cell, a neuronal stem cell and a mesenchymal stem cell. In an embodiment, the cell is an induced pluripotent stem (iPS) cell or a cell derived from an iPS cell, e.g., an iPS cell generated from the subject, modified to induce a mutation and differentiated into a clinically relevant cell such as a myeloid progenitor cell, an erythroid progenitor cell or a hematopoietic stem cell. In an embodiment, AAV is used to transduce the target cells, e.g., the target cells described herein.

Cells produced by the methods described herein may be used immediately. Alternatively, the cells may be frozen (e.g., in liquid nitrogen) and stored for later use. The cells will usually be frozen in 10% dimehtylsulfoxide (DMSO), 50% serum, 40% buffered medium, or some other such solution as is commonly used in the art to preserve cells at such freezing temperature and thawed in such a manner as commonly known in the art for thawing frozen cultured cells.

VII. Delivery, Formulations and Routes of Administration

The components, e.g., a Cas9 molecule and gRNA molecule can be delivered or formulated in a variety of forms, see, e.g., Tables 27-28. 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 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 27 provides examples of how the components can be formulated, delivered, or administered.

Table 27

from DNA, here from a single molecule.

DNA RNA 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

mRNA RNA 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.

mRNA 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.

Protein DNA In this embodiment, a Cas9 molecule, typically

an eaCas9 molecule, is provided as a protein,

and a gRNA is transcribed from DNA.

Protein RNA In this embodiment, an eaCas9 molecule is

provided as a protein, and a gRNA is provided

as transcribed or synthesized RNA.

Table 28 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 28

Vaccinia Virus YES Very NO DNA

Transient

Herpes Simplex YES Stable NO DNA

Virus

Non-Viral Cationic YES Transient Depends on Nucleic Acids

Liposomes what is and Proteins

delivered

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

DNA encoding Cas9 molecules (e.g., eaCas9 molecules) and/or gRNA molecules, 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 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 can be conjugated to molecules promoting uptake by the target cells (e.g., the target cells described herein).

In an embodiment, the Cas9- and/or gRNA-encoding DNA is delivered by a vector (e.g., viral vector/virus or plasmid).

A vector can comprise a sequence that encodes a Cas9 molecule and/or a gRNA molecule. 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 an embodiment, the promoter is recognized by RNA polymerase II (e.g., a CMV promoter). In another embodiment, the promoter is recognized by RNA polymerase III (e.g., a U6 promoter). In an embodiment, the promoter is a regulated promoter (e.g., inducible promoter). In another embodiment, the promoter is a constitutive promoter. In an embodiment, the promoter is a tissue specific promoter. In an embodiment, the promoter is a viral promoter. In another embodiment, the promoter is a non-viral promoter.

In an embodiment, the vector or delivery vehicle is a viral vector (e.g., for generation of recombinant viruses). In an embodiment, the virus is a DNA virus (e.g., dsDNA or ssDNA virus). In another embodiment, 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 an embodiment, the virus infects dividing cells. In another embodiment, the virus infects non-dividing cells. In an embodiment, the virus infects both dividing and non-dividing cells. In an embodiment, the virus can integrate into the host genome. In an embodiment, the virus is engineered to have reduced immunity, e.g., in human. In an embodiment, the virus is replication-competent. In another embodiment, 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 an embodiment, the virus causes transient expression of the Cas9 molecule and/or the gRNA molecule. In another embodiment, 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 an embodiment, the Cas9- and/or gRNA-encoding sequence is delivered by a recombinant retrovirus. In an embodiment, the retrovirus (e.g., Moloney murine leukemia virus) comprises a reverse transcriptase, e.g., that allows integration into the host genome. In an embodiment, the retrovirus is replication-competent. In another embodiment, 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 an embodiment, the Cas9- and/or gRNA-encoding sequence 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 an embodiment, the Cas9- and/or gRNA-encoding DNA is delivered by a recombinant adenovirus. In an embodiment, the adenovirus is engineered to have reduced immunity in human.

In an embodiment, the Cas9- and/or gRNA-encoding DNA is delivered by a recombinant AAV. In some embodiments, the AAV does not incorporate its geneome into that of a host cell, e.g., a target cell as describe herein. In an embodiment, 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 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. 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. 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 an embodiment, 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 EIB 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 an embodiment, 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 (e.g,, 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 an embodiment, the Cas9- and/or gRNA-encoding DNA 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., Fe₃Mn0₂) 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 (e.g., entrapment of the payload inside the nanoparticle). Exemplary organic nanoparticles include, e.g., SNALP liposomes that contain cationic lipids together with neutral helper lipids which are coated with polyethylene glycol (PEG) and protamine and nucleic acid complex coated with lipid coating.

Exemplary lipids for gene transfer are shown below in Table 29.

Table 29. Lipids Used for Gene Transfer

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 bromide DMRI Cationic

3 β- [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)]-dimethylammonium CLIP-1 Cationic 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-i-Butyl-N0-tetradecyl-3-tetradecylaminopropionamidine diC14-amidine Cationic

Octadecenolyoxy[ethyl-2-heptadecenyl-3 hydroxyethyl] imidazolinium DOTIM Cationic chloride

Nl -Cholesteryloxycarbonyl-3 ,7-diazanonane- 1 ,9-diamine CDAN Cationic

2-(3-[Bis(3-amino-propyl)-amino]propylamino)-N- RPR209120 Cationic ditetradecylcarbamoylme-ethyl-acetamide

1 ,2-dilinoleyloxy-3- dimethylaminopropane DLinDMA Cationic

2,2-dilinoleyl-4-dimethylaminoethyl-[ 1 ,3] - dioxolane DLin-KC2-DMA Cationic dilinoleyl- methyl -4-dimethylaminobutyrate DLin-MC3 -DMA Cationic

Exemplary polymers for gene transfer are shown below in Table 30.

Table 30. Polymers Used for Gene Transfer

Polymer Abbreviation

Poly(ethylene)glycol PEG

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(P-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(phosphazene)s PPZ

Poly (phosphoester) s PPE

Poly(phosphoramidate)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, 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, peptide-mediated delivery, or a combination thereof. Cas9-encoding and/or gRNA-encoding RNA can be conjugated to molecules to promote 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 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 in a vessel connected to a device (e.g., 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, transient cell compression or squeezing (e.g., as described in Lee, et al, 2012, Nano Lett 12: 6322-27), 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) with or without gRNA 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 Cas9 molecules (e.g., eaCas9 molecules, eiCas9 molecules or eiCas9 fusion protiens) with or without gRNA molecules in a vessel connected to a device (e.g., 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, intrarterial, intraosseous, intramuscular, intradermal, subcutaneous, intranasal and intraperitoneal routes. Components administered systemically may be modified or formulated to target the components to cells of the blood and bone marrow.

Local modes of administration include, by way of example, intra-bone marrow, intrathecal, and intra-cerebroventricular routes. In an embodiment, significantly smaller amounts of the components (compared with systemic approaches) may exert an effect when administered locally (for example, intra-bone marrow) 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 intra-bone marrow injection. Injections may be made directly into the bone marrow compartment of one or more than one bone. In an embodiment, nanoparticle or viral, e.g., AAV vector, delivery is via intra- bone marrow injection.

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, or gRNA molecule,. 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 lenti virus. 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 an embodiment, components described in Table 27 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 in Table 28.

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 an embodiment, the modified nucleic acids comprise one, two, three or more modified nucleotides. In an embodiment, 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 an embodiment, 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 an embodiment, 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 an embodiment, 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 an embodiment, 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 an embodiment, 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 an embodiment, 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 an embodiment, 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 an embodiment, 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 an embodiment, 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 an embodiment, 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 an embodiment, 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 an embodiment, 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 an embodiment, 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 an embodiment, 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 an embodiment, the nucleobase can include, for example, naturally-occurring and synthetic derivatives of a base.

Uracil

In an embodiment, 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-methyl-uridine

3 5 5

(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-methylaminomethyl-2-seleno-

5 2 5

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(Tm⁵s2U), 1 -taurinomethyl-4-thio-pseudouridine, 5-methyl-uridine (m⁵U, i.e., having the nucleobase deoxythymine), 1-methyl-pseudouridine (ηι'ψ), 5-methyl-2- thio-uridine (m⁵s2U), l-methyl-4-thio-pseudouridine 4-thio- 1-methyl-pseudouridine, 3- methyl-pseudouridine (m ψ), 2-thio-l -methyl -pseudouridine, 1 -methyl- 1-deaza-pseudouridine, 2-thio-l -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 3 U), l-methyl-3-(3-amino-3-carboxypropyl)pseudouridine (acp 3 ψ), 5- (isopentenylaminomethyl)uridine (inm⁵U), 5-(isopentenylaminomethyl)-2-thio-uridine

(inm⁵s2U), a-thio-uridine, 2'-0-methyl-uridine (Um), 5,2'-0-dimethyl-uridine (m⁵Um), 2'-0- methyl-pseudouridine (ψηι), 2-thio-2'-0-methyl-uridine (s2Um), 5-methoxycarbonylmethyl-2'- O-methyl-uridine (mem ⁵Um), 5-carbamoylmethyl-2'-0-methyl-uridine (ncm ⁵Um), 5- carboxymethylaminomethyl-2'-0-methyl-uridine (cmnm 5 Um), 3,2'-0-dimethyl-uridine (m 3 Um),

5- (isopentenylaminomethyl)-2'-0-methyl-uridine (inm⁵Um), 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 an embodiment, 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 an embodiment, 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 an embodiment, 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), 2 2

N2,7-dimethyl-guanosine (m ,7G), N2, N2,7-dimethyl-guanosine (m ,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-

2 2

methyl-guanosine (rri Gm), N2,N2-dimethyl-2'-0-methyl- guano sine (m ₂Gm), l-methyl-2'-0- methyl-guanosine (m'Gm), N2,7-dimethyl-2'-0-methyl-guanosine (rri ,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-1F, 2A-2C, 3A-3E, 4A-4E, 5A-5B, 6A-6D, 7A-7D, 8, 9A-9D, 10A-10D, 11, 12A-12D, 13A-13E, 14A-14B, 15A-15C, 16A- 16E, 17A-17C, 18A-18E, 19A-19E, 20A-20C, or 31.

As discussed above, transiently expressed or delivered nucleic acids can be prone to degradation by, e.g., cellular nucleases. Accordingly, in one aspect the modified gRNAs described herein can contain one or more modified nucleosides or nucleotides which introduce stability toward nucleases. While not wishing to be bound by theory it is also believed that certain modified gRNAs described herein can exhibit a reduced innate immune response when introduced into a population of cells, particularly the cells of the present invention. As noted above, 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.

While some of the exemplary modification 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 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 (ARCA)). 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 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 and guanosines can be replaced with modified adenosines and guanosines, e.g., with modifications at the 8-position, e.g., 8-bromo guanosine, or with any of the modified adenosines 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, heterocyclyl, 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, heterocyclyl, arylamino, diarylamino, heteroarylamino, or diheteroarylamino, ethylenediamine, or polyamino) and aminoalkoxy or 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, 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.

Governing gRNA molecules and the use thereof to limit the activity of a Cas9 system

Methods and compositions that use, or include, a nucleic acid, e.g., DNA, that encodes a Cas9 molecule or a gRNA molecule, can, in addition, use or include a "governing gRNA molecule." The governing gRNA can limit the activity of the other CRISPR/Cas components introduced into a cell or subject. In an embodiment, a gRNA molecule 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. 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 BCL11A gene (a target gene gRNA); or on more than one nucleic acid that encodes a CRISPR/Cas component, e.g., both (a) and (b). The governing gRNA molecule can complex with the Cas9 molecule to inactivate a component of the system. In an embodiment, a Cas9

molecule/governing gRNA molecule complex inactivates a nucleic acid that comprises the sequence encoding the Cas9 molecule. In an embodiment, a Cas9 molecule/governing gRNA molecule complex inactivates the nucleic acid that comprises the sequence encoding a target gene gRNA molecule. In an embodiment, a Cas9 molecule/governing gRNA molecule complex places temporal, level of expression, or other limits, on activity of the Cas9 molecule/target gene gRNA molecule complex. In an embodiment, a Cas9 molecule/governing gRNA molecule complex reduces off-target or other unwanted activity. In an embodiment, a governing gRNA molecule targets the coding sequence, or a control region, e.g., a promoter, for the CRISPR/Cas system component to be negatively regulated. For example, a governing gRNA can target the coding sequence for a Cas9 molecule, or a control region, e.g., a promoter, that regulates the expression of the Cas9 molecule coding sequence, or a sequence disposed between the two. In an embodiment, a governing gRNA molecule targets the coding sequence, or a control region, e.g., a promoter, for a target gene gRNA. In an embodiment, a governing gRNA, e.g., a Cas9- targeting or target gene gRNA-targeting, governing gRNA molecule, or a nucleic acid that encodes it, is introduced separately, e.g., later, than is the Cas9 molecule or a nucleic acid that encodes it. For example, a first vector, e.g., a viral vector, e.g., an AAV vector, can introduce nucleic acid encoding a Cas9 molecule and one or more target gene gRNA molecules, and a second vector, e.g., a viral vector, e.g., an AAV vector, can introduce nucleic acid encoding a governing gRNA molecule, e.g., a Cas9-targeting or target gene gRNA targeting, gRNA molecule. In an embodiment, the second vector can be introduced after the first. In another embodiment, a governing gRNA molecule, e.g., a Cas9-targeting or target gene gRNA targeting, governing gRNA molecule, or a nucleic acid that encodes it, can be introduced together, e.g., at the same time or in the same vector, with the Cas9 molecule or a nucleic acid that encodes it, but, e.g., under transcriptional control elements, e.g., a promoter or an enhancer, that are activated at a later time, e.g., such that after a period of time the transcription of Cas9 is reduced. In an embodiment, the transcriptional control element is activated intrinsically. In an embodiment, the transcriptional element is activated via the introduction of an external trigger.

Typically a nucleic acid sequence encoding a governing gRNA molecule, e.g., a Cas9- targeting gRNA molecule, is under the control of a different control region, e.g., promoter, than is the component it negatively modulates, e.g., a nucleic acid encoding a Cas9 molecule. In an embodiment, "different control region" refers to simply not being under the control of one control region, e.g., promoter, that is functionally coupled to both controlled sequences. In an embodiment, different refers to "different control region" in kind or type of control region. For example, the sequence encoding a governing gRNA molecule, e.g., a Cas9-targeting gRNA molecule, is under the control of a control region, e.g., a promoter, that has a lower level of expression, or is expressed later than the sequence which encodes is the component it negatively modulates, e.g., a nucleic acid encoding a Cas9 molecule.

By way of example, a sequence that encodes a governing gRNA molecule, e.g., a Cas9- targeting governing gRNA molecule, can be under the control of a control region (e.g., a promoter) described herein, e.g., human U6 small nuclear promoter, or human HI promoter. In an embodiment, a sequence that encodes the component it negatively regulates, e.g., a nucleic acid encoding a Cas9 molecule, can be under the control of a control region (e.g., a promoter) described herein, e.g., CMV, EF-la, MSCV, PGK, CAG promoters.

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 : Cloning and Initial Screening of 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 500-700bp long. For next generation sequencing, PCR amplicons may be 300-500bp 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: Screening of gRNAs for Targeting BCL11A

In order to identify gRNAs with the highest on target NHEJ efficiency, thirty exemplary S. pyogenes gRNAs were selected for testing (Table 31). The gRNAs tested target three different regions of the BCLA11A locus - 5' of a red blood cell enhancer, 3' of a red blood cell enhancer and downstream of the ATG start codon in exon 2 (specified in Table 31).

Table 31

BCL11A-2997W GUAAGUAUUUUCUUUCAUUG 20 3' of enhancer 14458

BCL11A-2998W G U A A U U A AG A A AG C AG U G U A 20 5' of enhancer 14459

BCL11A-2999W GUAUUUUCUU UCAUUGG 17 3' of enhancer 14460

BCL11A-32W UGGCAUCCAGGUCACGCCAG 20 Exon 2 14461

BCL11A-40W GAUGCUUUUUUCAUCUCGAU 20 Exon 2 14462

BCL11A-30W GCAUCCAAUCCCGUGGAGGU 20 Exon 2 14463

BCL11A-42W UUUUCAUCUCGAUUGGUGAA 20 Exon 2 14464

BCL11A-24W CCAGAUGAACUUCCCAUUGG 20 Exon 2 14465

BCL11A-53W AGGAGGUCAUGAUCCCCUUC 20 Exon 2 14466

BCL11A-79W CAUCCAGGUCACGCCAG 17 Exon 2 14467

BCL11A-90W GCUUUUUUCAUCUCGAU 17 Exon 2 14468

BCL11A-77W UCCAAUCCCGUGGAGGU 17 Exon 2 14469

BCL11A-92W UCAUCUCGAU UGGUGAA 17 Exon 2 14470

BCL11A-71W GAUGAACUUCCCAUUGG 17 Exon 2 14471

A DNA template comprised of an exemplary gRNA (including the target region and the S. pyogenes TRACR sequence) under the control of a U6 promoter was generated by a PCR StitchR reaction. This DNA template was subsequently transfected into 293 cells using

Lipofectamine 3000 along with a DNA plasmid encoding the S. pyogenes Cas9 downstream of a CMV promoter. Genomic DNA was isolated from the cells 48-72 hours post transfection. To determine the rate of modification at the BCL11A locus, the target region was amplified using a locus PCR with the primers listed in Table 32.

Table 32

After PCR amplification, a T7E1 -directed mismatch cleavage assay was performed on the PCR product. Briefly, this assay involves melting the PCR product followed by a re- annealing step. If gene modification has occurred, there will exist double stranded products that are not perfect matches due to some frequency of insertions or deletions. These double stranded products are sensitive to cleavage by a T7 endonuclease 1 enzyme at the site of mismatch. Therefore, the efficiency of cutting by the Cas9/gRNA complex was determined by analyzing the amount of T7E1 cleavage. The formula that was used to provide a measure of % NHEJ from the T7E1 cutting is the following: 100*(l-(l-(fraction cleaved))^A0.5). The results of this analysis are shown in Fig. 11. The top performing gRNAs in this assay were BCLl 1A-2981, BCLl 1A-2983, BCLl 1 A-2995, BCLl 1 A-32, BCLl 1 A-30, and BCLl 1 A-71.

Example 4: Deletion of the Erythroid Enhancer Elements Using Two gRNAs Flanking the Sequence

In order to test whether the erythroid enhancer sequence can be deleted using a two gRNA approach, two pairs of gRNA primers were tested in 293 cells. Pair number 1 comprised BCLl 1A-2983W and BCLl 1A-2981W while Pair number 2 comprised BCLl 1A-2995W and BCLl 1 A-2984W. In this example, a plasmid encoding S. pyogenes Cas9 downstream of a CMV promoter was delivered with either gRNA pair 1 or gRNA pair 2. The gRNAs were delivered as separate STITCHR products with each template comprising the U6 promoter, gRNA target sequence and S. pyogenes TRACR sequence. The DNA templates were delivered to 293 cells using lipid transfection (Lipofectamine 3000, Life Technologies). 72 hours post transfection, the cells were harvested and gDNA was isolated. To detect the deletion of the enhancer region of BCLl 1 A, PCR primers flanking the enhancer sequences were used to amplify the deletion event. The PCR product was TOPO cloned and sequenced by Sanger sequencing. The results of these analyses are presented in Fig. 12A-13B. As shown in Fig. 12A-13B, the deletion for both gRNA pairs that were delivered to the 293 cells were detected.

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

Other embodiments are within the following claims. What is claimed is:

1. A gRNA molecule comprising a targeting domain which is complementary with a target domain from the BCL11A 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 BT target knockout position.

3. The gRNA molecule of claim 1 or 2, wherein said targeting domain is configured to

target an early coding region or an enhancer region of the BCL11A gene.

4. The gRNA molecule of claim 1, wherein said targeting domain is configured to target an enzymatically inactive Cas9 (eiCas9) or an eiCas9 fusion protein, sufficiently close to a BT knockdown target position to reduce, decrease or repress expression of the BCL11A gene.

5. The gRNA molecule of any of claims 1, 2, or 4, wherein said targeting domain is

configured to target the promoter region of the BCL11A gene.

6. The gRNA molecule of any of claims 1-5, wherein said targeting domain comprises or consists of 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-1F, 2A-2C, 3A-3E, 4A-4E, 5A-5B, 6A-6D, 7A-7D, 8, 9A-9D, 10A-10D, 11, 12A-12D, 13A-13E, 14A-14B, 15A-15C, 16A- 16E, 17A-17C, 18A-18E, 19A-19E, 20A-20C, or 31.

7. The gRNA molecule of any of claims 1-5, wherein said targeting domain comprises or consists of a sequence that is the same as a targeting domain sequence from any of Tables 1A-1F, 2A-2C, 3A-3E, 4A-4E, 5A-5B, 6A-6D, 7A-7D, 8, 9A-9D, 10A-10D, 11, 12A- 12D, 13A-13E, 14A-14B, 15A-15C, 16A-16E, 17A-17C, 18A-18E, 19A-19E, 20A-20C, or 31.

8. The gRNA molecule of claim 1-3, 6, or 7, wherein said targeting domain is selected from those in Tables 1A-1F, 3A-3E, 4A-4E, 5A-5B, 12A-12D, 13A-13E, or 14A-14B.

9. The gRNA molecule of claim 1-3, 6, or 7, wherein said targeting domain is selected from those in Tables 6A-6D, 7A-7D, 8, 18A-18E, 19A-19E, or 20A-20C.

10. The gRNA molecule of claim 1 or 4-7, wherein said targeting domain is selected from those in Tables 2A-2C, 9A-9D, 10A-10D, 11, 15A-15C, 16A-16E, or 17A-17C.

11. The gRNA molecule of any of claims 1-10, wherein said targeting domain is selected from Table 31.

12. The gRNA molecule of any of claims 1-11, wherein said gRNA is a modular gRNA molecule.

13. The gRNA molecule of any of claimsl-11, wherein said gRNA is a chimeric gRNA molecule.

14. The gRNA molecule of any of claims 1-13, wherein said targeting domain is 16 nucleotides or more in length.

15. The gRNA molecule of any of claims 1-14, wherein said targeting domain is 17 nucleotides or more in length.

16. The gRNA molecule of any of claims 1-15, wherein said targeting domain is 18 nucleotides or more in length.

17. The gRNA molecule of any of claims 1-16, wherein said targeting domain is 19 nucleotides or more in length.

18. The gRNA molecule of any of claims 1-17, wherein said targeting domain is 20 nucleotides or more in length.

19. The gRNA molecule of any of claims 1-18, wherein said targeting domain is 21 nucleotides or more in length.

20. The gRNA molecule of any of claims 1-19, wherein said targeting domain is 22 nucleotides or more in length.

21. The gRNA molecule of any of claims 1-20, wherein said targeting domain is 23 nucleotides or more in length.

22. The gRNA molecule of any of claims 1-21, wherein said targeting domain is 24 nucleotides or more in length.

23. The gRNA molecule of any of claims 1-22, wherein said targeting domain is 25 nucleotides or more in length.

24. The gRNA molecule of any of claims 1-23, wherein said targeting domain is 26 nucleotides or more in length.

25. The gRNA molecule of any of claims 1-24, 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.

26. The gRNA molecule of any of claims 1-25, 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.

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 25 nucleotides in 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 30 nucleotides in length; and

a targeting domain of 17 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 40 nucleotides in length; and

a targeting domain of 17 nucleotides in length.

30. A nucleic acid that comprises: (a) sequence that encodes a gRNA molecule comprising a targeting domain that is complementary with a BT target domain in BCLllA gene.

31. The nucleic acid of claim 30, wherein said gRNA molecule is a gRNA molecule of any of claims 1-29.

32. The nucleic acid of claim 30 or 31, 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 BT target knockout position.

33. The nucleic acid of any of claims 30-32, wherein said targeting domain is configured to target an early coding region or an enhancer region of the BCL11A gene.

34. The nucleic acid of claim 30 or 31, wherein said targeting domain is configured to target an enzymatically inactive Cas9 (eiCas9) or an eiCas9 fusion protein, sufficiently close to a BT knockdown target position to reduce, decrease or repress expression of the BCL11A gene.

35. The nucleic acid of claim 30, 31, or 34, wherein said targeting domain is configured to target the promoter region of the BCL11A gene.

36. The nucleic acid of any of claims 30-35, wherein said targeting domain comprises or consists of 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-1F, 2A-2C, 3A-3E, 4A-4E, 5A-5B, 6A-6D, 7A-7D, 8, 9A-9D, 10A-10D, 11, 12A-12D, 13A-13E, 14A-14B, 15A-15C, 16A- 16E, 17A-17C, 18A-18E, 19A-19E, 20A-20C, or 31.

37. The nucleic acid of any of claims 30-36, wherein said targeting domain comprises or consists of 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-1F, 2A-2C, 3A-3E, 4A-4E, 5A-5B, 6A-6D, 7A-7D, 8, 9A-9D, 10A-10D, 11, 12A-12D, 13A-13E, 14A-14B, 15A-15C, 16A- 16E, 17A-17C, 18A-18E, 19A-19E, 20A-20C, or 31.

38. The nucleic acid of any of claims 30-37, wherein said gRNA is a modular gRNA

molecule.

39. The nucleic acid of any of claims 30-37, wherein said gRNA is a chimeric gRNA

molecule.

40. The nucleic acid of any of claims 30-39, wherein said targeting domain is 16 nucleotides or more in length.

41. The nucleic acid of any of claims 30-40, wherein said targeting domain is 17 nucleotides in length.

42. The nucleic acid of any of claims 30-40, wherein said targeting domain is 18 nucleotides in length.

43. The nucleic acid of any of claims 30-40, wherein said targeting domain is 19 nucleotides in length.

44. The nucleic acid of any of claims 30-40, wherein said targeting domain is 20 nucleotides in length.

45. The nucleic acid of any of claims 30-40, wherein said targeting domain is 21 nucleotides or more in length.

46. The nucleic acid of any of claims 30-40, wherein said targeting domain is 22 nucleotides in length.

47. The nucleic acid of any of claims 30-40, wherein said targeting domain is 23 nucleotides in length.

48. The nucleic acid of any of claims 30-40, wherein said targeting domain is 24 nucleotides in length.

49. The nucleic acid of any of claims 30-40, wherein said targeting domain is 25 nucleotides in length.

50. The nucleic acid of any of claims 30-40, wherein said targeting domain is 26 nucleotides in length.

51. The nucleic acid of any of claims 30-50, 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.

52. The nucleic acid of any of claims 30-51, 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.

53. The nucleic acid of any of claims 30-52, 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.

54. The nucleic acid of any of claims 30-53, 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.

55. The nucleic acid of any of claims 30-54, 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.

56. The nucleic acid of any of claims 30-55, further comprising: (b) sequence that encodes a Cas9 molecule.

57. The nucleic acid of claim 56, wherein said Cas9 molecule is an eaCas9 molecule.

58. The nucleic acid of claim 57, wherein said eaCas9 molecule comprises a nickase

molecule.

59. The nucleic acid of claim 57, wherein said eaCas9 molecule forms a double strand break in a target nucleic acid.

60. The nucleic acid of any of claims 57 or58, wherein said eaCas9 molecule forms a single strand break in a target nucleic acid.

61. The nucleic acid of any of claims 57, 58 or 60, 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.

62. The nucleic acid of any of claims 57, 58 or 60, 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.

63. The nucleic acid of any of claims 57, 58 or 60, wherein said eaCas9 molecule comprises HNH-like domain cleavage activity but has no, or no significant, N-terminal RuvC-like domain cleavage activity.

64. The nucleic acid of any of claims 57, 58, 60, or 63, wherein said eaCas9 molecule is an HNH-like domain nickase.

65. The nucleic acid of any of claims 57,58, 60, 63, or 64, wherein said eaCas9 molecule comprises a mutation at D10.

66. The nucleic acid of any of claims 57,58 or 60, wherein said eaCas9 molecule comprises N-terminal RuvC-like domain cleavage activity but has no, or no significant, HNH-like domain cleavage activity.

67. The nucleic acid of any of claims 57,58, 60, or 66, wherein said eaCas9 molecule is an N- terminal RuvC-like domain nickase.

68. The nucleic acid of any of claims 57, 58, 60, 66, or 67, wherein said eaCas9 molecule comprises a mutation at H840 or N863.

69. The nucleic acid of claim 56, wherein said Cas9 molecule is an eiCas9 molecule.

70. The nucleic acid of claim 69, wherein said Cas9 molecule is an eiCas9 fusion protein molecule.

71. The nucleic acid of claim 69 or 70, wherein the eiCas9 fusion protein molecule is an eiCas9-transcription repressor domain fusion or eiCas9-chromatin modifying protein fusion.

72. The nucleic acid of any of claims 30-71, 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 BCL11A gene.

73. The nucleic acid of claim 72, wherein said second gRNA molecule is a gRNA molecule of any of claims 1-29.

74. The nucleic acid of claim 72 or 73, wherein said targeting domain of said second gRNA molecule 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 BT target knockout position.

75. The nucleic acid of any of claims 72-74, wherein said targeting domain of said second gRNA is configured to target an early coding region or an enhancer region of the

BCL11A gene.

76. The nucleic acid of claim 72 or 73, wherein said targeting domain of said second gRNA molecule is configured to target an enzymatically inactive Cas9 (eiCas9) or an eiCas9 fusion protein, sufficiently close to a BT knockdown target position to reduce, decrease or repress expression of the BCL11A gene.

77. The nucleic acid of any of claims 72, 73, or 76, wherein said targeting domain of said second gRNA molecule is configured to target the promoter region of the BCL11A gene.

78. The nucleic acid of claim 72-77, wherein said targeting domain of said second gRNA molecule comprises or consists of 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-1F, 2A-2C, 3A-3E, 4A-4E, 5A-5B, 6A-6D, 7A-7D, 8, 9A-9D, 10A-10D, 11, 12A-12D, 13A-13E, 14A-14B, 15A-15C, 16A-16E, 17A-17C, 18A-18E, 19A-19E, 20A-20C, or 31.

79. The nucleic acid of claim 72-78, wherein said targeting domain of said second gRNA molecule comprises or consists of a sequence that is the same as a targeting domain sequence from any of Tables 1A-1F, 2A-2C, 3A-3E, 4A-4E, 5A-5B, 6A-6D, 7A-7D, 8, 9A-9D, 10A-10D, 11, 12A-12D, 13A-13E, 14A-14B, 15A-15C, 16A-16E, 17A-17C, 18A-18E, 19A-19E, 20A-20C, or 31.

80. The nucleic acid of any of claims 72-79, wherein said second gRNA molecule is a

modular gRNA molecule.

81. The nucleic acid of any of claims 72-79, wherein said second gRNA molecule is a

chimeric gRNA molecule.

82. The nucleic acid of any of claims 72-81, wherein said targeting domain is 16 nucleotides or more in length.

83. The nucleic acid of any of claims 72-82, wherein said targeting domain is 17 nucleotides in length.

84. The nucleic acid of any of claims 72-82, wherein said targeting domain is 18 nucleotides in length.

85. The nucleic acid of any of claims 72-82, wherein said targeting domain is 19 nucleotides in length.

86. The nucleic acid of any of claims 72-82, wherein said targeting domain is 20 nucleotides in length.

87. The nucleic acid of any of claims 72-86, 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.

88. The nucleic acid of any of claims 72-87, wherein said second gRNA molecule comprises: a linking domain of no more than 25 nucleotides in length;

89. The nucleic acid of any of claims 72-88, 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.

90. The nucleic acid of any of claims 72-89, wherein said second gRNA molecule comprises: a linking domain of no more than 25 nucleotides in length;

91. The nucleic acid of any of claims 72-90, wherein said second gRNA molecule comprises: a linking domain of no more than 25 nucleotides in length;

92. The nucleic acid of any of claims 72-91, further comprising a third gRNA molecule.

93. The nucleic acid of claim 92, further comprising a fourth gRNA molecule.

94. The nucleic acid of any of claims 30-71, wherein said nucleic acid does not comprise (c) a sequence that encodes a second gRNA molecule.

95. The nucleic acid of any of claims 56-94, wherein each of (a) and (b) is present on the same nucleic acid molecule.

96. The nucleic acid of claim 95, wherein said nucleic acid molecule is an AAV vector.

97. The nucleic acid of any of claims 56-94, wherein: (a) is present on a first nucleic acid molecule; and (b) is present on a second nucleic acid molecule.

98. The nucleic acid of claim 97, wherein said first and second nucleic acid molecules are AAV vectors.

99. The nucleic acid of any of claims 72-93 or 95-98, wherein each of (a) and (c) is present on the same nucleic acid molecule.

100. The nucleic acid of claim 99, wherein said nucleic acid molecule is an AAV

vector.

101. The nucleic acid of any of claims 72-93 or 95-98, wherein: (a) is present on a first nucleic acid molecule; and (c) is present on a second nucleic acid molecule.

102. The nucleic acid of claim 101, wherein said first and second nucleic acid

molecules are AAV vectors.

103. The nucleic acid of any of claims 71-93, 95, 96, 99, or 100, wherein each of (a), (b), and (c) are present on the same nucleic acid molecule.

104. The nucleic acid of claim 103, wherein said nucleic acid molecule is an AAV vector.

105. The nucleic acid of any of claims 72-93 or 95-102, 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.

106. The nucleic acid of claim 105, wherein said first and second nucleic acid

molecules are AAV vectors.

107. The nucleic acid of claim 72-93, 97, 98, 101, 102, 105, or 106, wherein: (a) is present on a first nucleic acid molecule; and (b) and (c) are present on a second nucleic acid molecule.

108. The nucleic acid of claim 107, wherein said first and second nucleic acid

molecules are AAV vectors.

109. The nucleic acid of claim 72-93, 97-100, 105, or 106, wherein: (b) is present on a first nucleic acid molecule; and (a) and (c) are present on a second nucleic acid molecule.

110. The nucleic acid of claim 109, wherein said first and second nucleic acid

molecules are AAV vectors.

111. The nucleic acid of claim 72-93, 95, 96, 101, 102, 105, or 106, wherein: (c) is present on a first nucleic acid molecule; and (b) and (a) are present on a second nucleic acid molecule.

112. The nucleic acid of claim 111, wherein said first and second nucleic acid

molecules are AAV vectors.

113. The nucleic acid of any of claims 97, 101, 105, 107, 109, or 111, wherein said first nucleic acid molecule is other than an AAV vector and said second nucleic acid molecule is an AAV vector.

114. The nucleic acid of any of claims 30-113, wherein said nucleic acid comprises a promoter operably linked to the sequence that encodes said gRNA molecule of (a).

115. The nucleic acid of claims 72-93 or 95-114, wherein said nucleic acid comprises a second promoter operably linked to the sequence that encodes the second gRNA molecule of (c).

116. The nucleic acid of claim 115, wherein the promoter and second promoter differ from one another.

117. The nucleic acid of claim 115, wherein the promoter and second promoter are the same.

118. The nucleic acid of any of claims 72-117, wherein said nucleic acid comprises a promoter operably linked to the sequence that encodes the Cas9 molecule of (b).

119. A composition comprising the (a) gRNA molecule of any of claims 1-29.

120. The composition of claim 119, further comprising (b) a Cas9 molecule of any of claims 56-71.

121. The composition of any of claims 119 or 120, further comprising (c) a second gRNA molecule of any of claims 72-91.

122. The composition of claim 121, further comprising a third gRNA molecule.

123. The composition of claim 122, further comprising a fourth gRNA molecule.

124. A method of altering a cell comprising contacting said cell with:

(a) a gRNA of any of claims 1-29;

(b) a Cas9 molecule of any of claims 56-71; and

optionally, (c) a second gRNA molecule of any of claims 72-91.

125. The method of claim 124, further comprising a third gRNA molecule.

126. The method of claim 125, further comprising a fourth gRNA molecule.

127. The method of claim 115, comprising contacting said cell with (a), (b), and (c).

128. The method of any of claims 124-127, wherein said cell is from a subject

suffering from BT or BTM.

129. The method of any of claims 124-128, wherein said cell is from a subject who could benefit from a mutation at a BT target position of the BCL11A gene.

130. The method of any of claims 124-129, wherein said cell is an erythroid cell.

131. The method of any of claims 124-129, wherein said cell is an erythroid cell

precursor cell.

132. The method of claim 131, wherein said erythorid cell precursor cell is a

hematopoietic stem cell.

133. The method of claim 131 or 132, wherein said erythorid cell precursor cell is a CD34+ hematopoietic stem cell.

134. The method of any of claims 124-133, wherein said contacting step is performed ex vivo.

135. The method of claim 134, wherein said contacted cell is returned to said subject's body.

136. The method of any of claims 124-133, wherein said contacting step is performed in vivo.

137. The method of any of claims 124-136, comprising acquiring knowledge of the sequence of the BT target position in said cell.

138. The method of claim 137, comprising acquiring knowledge of the sequence of the BT target position in said cell by sequencing a portion of the BCL11A gene.

139. The method of any of claims 124-138, comprising inducing a BT target position mutation.

140. The method of any of claims 124-139, wherein the contacting step comprises contacting said cell with a nucleic acid that encodes at least one of (a), (b), and (c).

141. The method of any of claims 124-140, wherein contacting comprises contacting the cell with a nucleic acid of any of claims 30-118.

142. The method of any of claims 124-141, wherein the contacting step comprises delivering to said cell said Cas9 molecule of (b) and a nucleic acid which encodes and (a) and optionally (c).

143. The method of any of claims 124-141, wherein the contacting step comprises delivering to said cell said Cas9 molecule of (b), said gRNA molecule of (a) and optionally said second gRNA molecule of (c).

144. The method of any of claims 124-141, wherein the contacting step 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).

145. A method of treating a subject, comprising contacting a subject, or a cell from said subject, with:

(a) a gRNA of any of claims 1-29;

(b) a Cas9 molecule of any of claims 56-71; and

optionally, (c) a second gRNA of any of claims 72-91.

146. The method of claim 145, further comprising contacting the subject or a cell from said subject with a third gRNA molecule.

147. The method of claim 146, further comprising contacting the subject or a cell from said subject with a fourth gRNA molecule.

148. The method of any of claims 145-147, further comprising contacting said subject or a cell from said subject with (a), (b), and (c).

149. The method of any of claims 145-148, wherein said subject is suffering from BT, e.g., BTM.

150. The method of any of claims 145-149, wherein said subject would benefit from a mutation at the BT target position of the BCL11A gene.

151. The method of any of claims 145-150, comprising acquiring knowledge of the sequence of the BT target position in said subject.

152. The method of claim 151, comprising acquiring knowledge of the sequence of the BT target position in said subject by sequencing a portion of the BCL11A gene.

153. The method of claim 145-152, comprising inducing a BT target position mutation in the BCL11A gene.

154. The method of any of claims 145-153, wherein a cell of said subject is contacted ex vivo with (a), (b), and optionally (c).

155. The method of claim 154, wherein said cell is returned to the subject's body.

156. The method of any of claims 145-153, comprising introducing a cell into said subject's body, wherein said cell subject is contacted ex vivo with (a), (b), and optionally (c).

157. The method of any of claims 145-153, wherein said contacting step is performed in vivo.

158. The method of any of claims 145-153 or 157, wherein said contacting step

comprises intravenous injection.

159. The method of any of claims 145-158, comprising contacting said subject or a cell from said subject with a nucleic acid that encodes at least one of (a), (b), and (c).

160. The method of any of claims 145-159, comprising contacting said subject or a cell from said subject with a nucleic acid of any of claims 30-118.

161. The method of any of claims 145-160, wherein the contacting step comprises delivering to said subject said Cas9 molecule of (b) and a nucleic acid which encodes and

(a) and optionally (c).

162. The method of any of claims 145-160, wherein the contacting step comprises delivering to said subject said Cas9 molecule of (b), and said gRNA of (a) and optionally said second gRNA of (c).

163. The method of any of claims 145-160, 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).

164. A reaction mixture comprising a gRNA, a nucleic acid, or a composition

described herein, and a cell from a subject having BT, or a subject which would benefit from a mutation at a BT target position of the BCL11A gene.

165. A kit comprising, (a) gRNA molecule of any of claims 1-29, or nucleic acid that encodes said gRNA, and one or more of the following:

(b) a Cas9 molecule of any of claims 56-71;

(c) a second gRNA molecule of any of claims 72-91; and

(d) nucleic acid that encodes one or more of (b) and (c).

166. The kit of claim 165, comprising nucleic acid that encodes one or more of (a), (b) and (c).

167. The kit of claim 165 or 166, further comprising a third gRNA molecule targeting a BCL11A target position.

168. The kit of claim 167, further comprising a fourth gRNA molecule targeting a

BCL11A target position.

169. A gRNA molecule of any of claims 1-29 for use in treating BT or BTM in a subject.

170. The gRNA molecue of claim 169, wherein the gRNA molecule in used in

combination with (b) a Cas9 molecule of any of claims 56-71.

171. The gRNA molecule of claim 169 or 170, wherein the gRNA molecule is used in combination with (c) a second gRNA molecule of any of claims 72-91.

172. Use of a gRNA molecule of any of claims 1-29 in the manufacture of a

medicament for treating BT or BTM in a subject.

173. The use of claim 172, wherein the medicament further comprises (b) a Cas9 molecule of any of claims 56-71.

174. The use of claim 172 or 173, wherein the medicament further comprises (c) a second gRNA molecule of any of claims 72-91.

175. A composition of any of claims 119-123 for use in treating BT or BTM in a subject.