US20230026726A1 - Crispr/cas-related methods and compositions for treating sickle cell disease - Google Patents

Abstract

CRISPR/CAS-related compositions and methods for treatment of Sickle Cell Disease (SCD) are disclosed.

Description

REFERENCE TO RELATED APPLICATIONS
• The present application is a continuation of U.S. application Ser. No. 15/129,367, filed Sep. 26, 2016, which is a national phase of International Application No. PCT/US2015/022856, filed Mar. 26, 2015, which claims the benefit of U.S. Provisional Application No. 61/970,588, filed Mar. 26, 2014, and U.S. Provisional Application No. 62/084,487, filed Nov. 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 Sickle Cell Disease (SCD).
SEQUENCE LISTING
• This application contains a Sequence Listing, which was submitted in ASCII format via EFS-Web, and is hereby incorporated by reference in its entirety. The ASCII copy, created on Jan. 19, 2022, is named SequenceListing.txt and is 3,905 KB in size.
BACKGROUND
• Sickle Cell Disease (SCD), also known as Sickle Cell Anemia (SCA), is a common inherited hematologic disease. It affects 80,000-90,000 people in the United States. It is common in people of African descent and in Hispanic-Americans with the prevalence of SCD being 1 in 500 and 1 in 1,000, respectively.
• SCD is caused by a mutation 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, G gamma chain. The alpha-globin gene is located on chromosome 16. A point mutation (e.g., GAG→GTG) results in the substitution of valine for glutamic acid at amino acid position 6 in exon 1 of the HBB gene. Beta hemoglobin chains with this mutation are expressed as HbS. The disease is inherited in an autosomal recessive manner, so that only patients with two HbS alleles have SCD. Subjects who have sickle cell trait (are heterozygous for HbS) only display a phenotype if they are severely dehydrated or oxygen deprived.
• Normal adult hemoglobin (Hb) is composed of a tetramer made from two alpha-globin chains and two beta-globin chains. In SCD, the valine at position 6 of the beta-chain is hydrophobic and causes a change in conformation of the beta-globin protein when it is not bound to oxygen. HbS is more likely to polymerize and leads to the characteristic sickle shaped red blood cells (RBCs) found in SCD.
• Sickle shape RBCs cause multiple manifestations of disease, which include, e.g., anemia, sickle cell crises, vaso-occlusive crises, aplastic crises and acute chest syndrome. The disease has varous manifestations, e.g., vaso-occlusive crisis, splenic sequestration crisis and anemia. Subjects may also suffer from acute chest crisis and infarcts of extremities, end organs and central nervous system. Treatment includes, e.g., hydration, transfusion and analgesics. Treatment of SCD also includes, e.g., the use of hydroxyurea, supplementation with folic acid, and penicillin prophylaxis during childhood. Bone marrow transplants have been demonstrated to cure SCD.
• Thus, there remains a need for additional methods and compositions that can be used to treat SCD.
SUMMARY OF THE INVENTION
• Methods and compositions discussed herein, provide for the treatment and prevention of Sickle Cell Disease (SCD), also known as Sickle Cell Anemia (SCA). SCD is an inherited hematologic disease.
• In healthy individuals, two beta-globin molecules pair with two alpha-globin molecules to form normal hemoglobin (Hb). In SCD, mutations in the beta-globin (HBB) gene, e.g., a point mutation (GAG→GTG) that results in the substitution of valine for glutamic acid at amino acid position 6 of the beta-globin molecule, cause production of sickle hemoglobin (HbS). HbS is more likely to polymerize and leads to the characteristic sickle shaped red blood cells (RBCs). Sickle shaped RBCs give rise to multiple manifestations of disease, such as, anemia, sickle cell crises, vaso-occlusive crises, aplastic crises and acute chest syndrome. Alpha-globin can also pair with fetal hemoglobin (HbF), which significantly moderates the severe anemia and other symptoms of SCD. However, the expression of HbF is negatively regulated by the BCL11A gene product.
• Methods and compositions disclosed herein provide a number of approaches for treating SCD. As is discussed in more detail below, methods described herein provide for treating SCD by correcting a target position in the HBB gene to provide corrected, or functional, e.g., wild type, beta-globin. Methods and compositions discussed herein can be used to treat or prevent SCD by altering the BCL11A gene (also known as B-cell CLL/lymphoma 11A, 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 SCD disease phenotypes.
• In one aspect, methods and compositions discussed herein, provide for the correction of the underlying genetic cause of SCD, e.g., the correction of a mutation at a target position in the HBB gene, e.g., correction of a mutation at amino acid position 6, e.g., an E6V substitution in the HBB gene.
• Mutations in the HBB gene (also known as beta-globin and CD113t-C) have been shown to cause SCD. Mutations leading to SCD can be described based on their target positions in the HBB gene. In an embodiment, the target position is E6, e.g., E6V, in the HBB gene.
• “SCD target point position”, as used herein, refers to a target position in the HBB gene, typically a single nucleotide, which, if mutated, can result in a protein having a mutant amino acid and give rise to SCD. In an embodiment, the SCD target position is the target position at which a change can give rise to an E6 mutant protein, e.g., a protein having an E6V substitution.
• While much of the disclosure herein is presented in the context of the mutation in the HBB gene that gives rise to an E6 mutant protein (e.g., E6V mutant protein), the methods and compositions herein are broadly applicable to any mutation, e.g., a point mutation or a deletion, in the HBB gene that gives rise to SCD.
• While not wishing to be bound by theory, it is believed that, in an embodiment, a mutation at an SCD target point position in the HBB gene is corrected, e.g., by homology directed repair (HDR), as described herein.
• In one aspect, methods and compositions discussed herein may be used to alter the BCL11A gene to treat or prevent SCD, by targeting the BCL11A gene, e.g., coding or non-coding regions of the BCL11A gene. Altering the BCL11A gene herein refers to reducing or eliminating (1) BCL11A 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 BCL11A 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 BCL11A gene by the insertion or deletion of one or more nucleotides mediated by Cas9 (e.g., enzymatically active Cas9 (eaCas9), e.g., Cas9 nuclease or Cas9 nickase) as described below. This type of alteration is also referred to as “knocking out” the BCL11A gene.
• In another embodiment, the method provides an alteration that does not comprise nucleotide insertion or deletion in the BCL11A gene and is mediated by enzymatically inactive Cas9 (eiCas9) or an eiCas9-fusion protein, as described below. This type of alteration is also referred to as “knocking down” the BCL11A gene.
• In an embodiment, the methods and compositions discussed herein may be used to alter the BCL11A gene to treat or prevent SCD by knocking out one or both alleles of the BCL11A gene. In an embodiment, the coding region (e.g., an early coding region) of the BCL11A gene, is targeted to alter the gene. In an embodiment, a non-coding region of the BCL11A 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. BCL11A erythroid enhancer comprises an approximate 12.4 kb fragment of BCL11A intron2, located between approximate+52.0 to +64.4 kilobases (kb) from the Transcription Start Site (TSS+52 kb to TSS+64.4 kb, see FIG. 10 ). It's 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+62 kb, TSS+58 kb and TSS+55 kb are located in this region. Deoxyribonuclease I sensitivity is a marker for gene regulatory elements. While not wishing to be bound by theory, it's believed that deleting the ehancer region (e.g., TSS+52 kb to TSS+64.4 kb) may reduce or eliminate BCL11A expression in erythroid precursors which leads to gamma globin derepression while sparing BCL11A 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). In an embodiment, a targeted knockout approach alters the BCL11A gene. In an embodiment, a targeted knockout approach reduces or eliminates expression of functional BCL11A gene product. In an embodiment, targeting affects one or both alleles of the BCL11A gene. In an embodiment, an enhancer disruption approach reduces or eliminates expression of functional BCL11A gene product in the erythroid lineage.
• “SCD target knockout position”, as used herein, refers to a position in the BCL11A gene, which if altered, e.g., disrupted by insertion or deletion of one or more nucleotides, e.g., by NHEJ-mediated alteration, results in reduction or elimination of expression of functional BCL11A gene product. In an embodiment, the position is in the BCL11A coding region, e.g., an early coding region. In an embodiment, the position is in the BCL11A non-coding region, e.g., an enhancer region.
• In an embodiment, methods and compositions discussed herein, provide for altering (e.g., knocking out) the BCL11A gene. In an embodiment, knocking out the BCL11A 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 BCL11A gene, or (2) deletion (e.g., NHEJ-mediated deletion) of a genomic sequence including the erythroid enhancer of the BCL11A gene,
• In an embodiment, the SCD target knockout position is altered by genome editing using the CRISPR/Cas9 system. The SCD 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 SCD target knockout position or to delete (e.g., mediated by NHEJ) a genomic sequence including the erythroid enhancer of the BCL11A 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 BCL11A 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 BCL11A 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 BCL11A 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 BCL11A 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 at the in the BCL11A gene (one 5′ and the other one 3′ to the erythroid enhancer) to remove (e.g., delete) the genomic sequence including the erythroid enhancer. 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. 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 SCD 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. 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 SCD 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) 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 BCL11A gene.
• “SCD 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) 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) or an eiCas9 fusion protein (e.g., an eiCas9 fused to a transcription repressor domain), sufficiently close to a SCD target knockdown position to reduce, decrease or repress expression of the BCL11A gene.
• “SCD target position”, as used herein, refers to any of an SCD target point position, SCD target knockout position, or SCD target knockdown position, as described herein.
• In one aspect, disclosed herein is a gRNA molecule, e.g., an isolated or non-naturally occurring gRNA molecule, comprising a targeting domain which is complementary with a target domain from the HBB gene or 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 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 an embodiment, a point mutation in the HBB gene, e.g., at E6, e.g., E6V, is targeted, e.g., for correction. In an embodiment, the targeting domain of a gRNA molecule comprises a sequence that is the same as, or differs by no more than 1, 2, 3, 4, or 5 nucleotides from, a targeting domain sequence from any one of Tables 1A-1D. In an embodiment, the targeting domain is selected from those in Tables 1A-1D. For example, in an embodiment, the targeting domain is:

• 	(SEQ ID NO: 387)
  	AAGGUGAACGUGGAUGAAGU;
  	(SEQ ID NO: 388)
  	GUAACGGCAGACUUCUCCUC;
  	(SEQ ID NO: 389)
  	GUGAACGUGGAUGAAGU;
  	or
  	(SEQ ID NO: 390)
  	ACGGCAGACUUCUCCUC.

• In an embodiment, when the SCD target point position is E6, e.g., E6V, and two gRNAs are used to position two breaks, e.g., two single stranded breaks, in the target nucleic acid sequence, the targeting domain of each guide RNA is selected from one of Tables 1A-1D.
• In an embodiment, a point mutation in the HBB gene, e.g., at E6, e.g., E6V, is targeted, e.g., for correction. In an embodiment, the targeting domain of a gRNA molecule comprises a sequence that is the same as, or differs by no more than 1, 2, 3, 4, or 5 nucleotides from, a targeting domain sequence from any one of Tables 13A-13D. In an embodiment, the targeting domain is selected from those in Tables 13A-13D. For example, in an embodiment, the targeting domain is:

• 	(SEQ ID NO: 6803)
  	GGUGCACCUGACUCCUG;
  	or
  	(SEQ ID NO: 6804)
  	GUAACGGCAGACUUCUCCAC.

• In an embodiment, when the SCD target point position is E6, e.g., E6V, and two gRNAs are used to position two breaks, e.g., two single stranded breaks, in the target nucleic acid sequence, the targeting domain of each guide RNA is selected from one of Tables 13A-13D.
• In an embodiment, a point mutation in the HBB gene, e.g., at E6, e.g., E6V, is targeted, e.g., for correction. In an embodiment, the targeting domain of a gRNA molecule comprises a sequence that is the same as, or differs by no more than 1, 2, 3, 4, or 5 nucleotides from, a targeting domain sequence from any one of Tables 14A-14C. In an embodiment, the targeting domain is selected from those in Tables 14A-14C.
• In an embodiment, when the SCD target point position is E6, e.g., E6V, and two gRNAs are used to position two breaks, e.g., two single stranded breaks, in the target nucleic acid sequence, each guide RNA is selected from one of Tables 14A-14C.
• In an embodiment, a point mutation in the HBB gene, e.g., at E6, e.g., E6V, is targeted, e.g., for correction. In an embodiment, the targeting domain of a gRNA molecule comprises a sequence that is the same as, or differs by no more than 1, 2, 3, 4, or 5 nucleotides from, a targeting domain sequence from any one of Tables 24A-24D. In an embodiment, the targeting domain is selected from those in Tables 24A-24D.
• In an embodiment, when the SCD target point position is E6, e.g., E6V, and two gRNAs are used to position two breaks, e.g., two single stranded breaks, in the target nucleic acid sequence, the targeting domain of each guide RNA is selected from one of Tables 24A-24D.
• In an embodiment, a point mutation in the HBB gene, e.g., at E6, e.g., E6V, is targeted, e.g., for correction. In an embodiment, the targeting domain of a gRNA molecule comprises a sequence that is the same as, or differs by no more than 1, 2, 3, 4, or 5 nucleotides from, a targeting domain sequence from any one of Tables 25A-25B. In an embodiment, the targeting domain is selected from those in Tables 25A-25B.
• In an embodiment, when the SCD target point position is E6, e.g., E6V, and two gRNAs are used to position two breaks, e.g., two single stranded breaks, in the target nucleic acid sequence, the targeting domain of each guide RNA is selected from one of Tables 25A-25B.
• In an embodiment, a point mutation in the HBB gene, e.g., at E6, e.g., E6V, is targeted, e.g., for correction. In an embodiment, the targeting domain of a gRNA molecule comprises a sequence that is the same as, or differs by no more than 1, 2, 3, 4, or 5 nucleotides from, a targeting domain sequence from Table 26. In an embodiment, the targeting domain is selected from those in Table 26.
• In an embodiment, when the SCD target point position is E6, e.g., E6V, and two gRNAs are used to position two breaks, e.g., two single stranded breaks, in the target nucleic acid sequence, the targeting domain of each guide RNA is selected from Table 26. 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 2A-2F. In an embodiment, the targeting domain is selected from those in Tables 2A-2F. In another embodiment, the targeting domain is:

• 	(SEQ ID NO: 486)
  	UGGCAUCCAGGUCACGCCAG;
  	(SEQ ID NO: 487)
  	GAUGCUUUUUUCAUCUCGAU;
  	(SEQ ID NO: 488)
  	GCAUCCAAUCCCGUGGAGGU;
  	(SEQ ID NO: 489)
  	UUUUCAUCUCGAUUGGUGAA;
  	(SEQ ID NO: 490)
  	CCAGAUGAACUUCCCAUUGG;
  	(SEQ ID NO: 491)
  	AGGAGGUCAUGAUCCCCUUC;
  	(SEQ ID NO: 492)
  	CAUCCAGGUCACGCCAG;
  	(SEQ ID NO: 493)
  	GCUUUUUUCAUCUCGAU;
  	(SEQ ID NO: 494)
  	UCCAAUCCCGUGGAGGU;
  	(SEQ ID NO: 495)
  	UCAUCUCGAUUGGUGAA;
  	(SEQ ID NO: 496)
  	GAUGAACUUCCCAUUGG;
  	or
  	(SEQ ID NO: 497)
  	AGGUCAUGAUCCCCUUC.

• In an embodiment, when the SCD 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 stranded breaks or two double stranded breaks, or a combination of single strand and double strand breaks, e.g., to create one or more indels, in the target nucleic acid sequence, the targeting domain of each guide RNA is selected from one of Tables 2A-2F.
• 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 Table 4A-4E. In an embodiment, the targeting domain is selected from those in Table 4A-4E. In another embodiment, the targeting domain is:

• 	(SEQ ID NO: 3073)
  	GAGCUCCAUGUGCAGAACGA;
  	(SEQ ID NO: 3074)
  	GAGCUCCCAACGGGCCG;
  	(SEQ ID NO: 3075)
  	GAGUGCAGAAUAUGCCCCGC;
  	(SEQ ID NO: 3076)
  	GAUAAACAAUCGUCAUCCUC;
  	(SEQ ID NO: 3077)
  	GAUGCCAACCUCCACGGGAU;
  	(SEQ ID NO: 3078)
  	GCAGAAUAUGCCCCGCA;
  	(SEQ ID NO: 3079)
  	GCAUCCAAUCCCGUGGAGGU;
  	(SEQ ID NO: 3080)
  	GCCAACCUCCACGGGAU;
  	(SEQ ID NO: 3081)
  	GCUCCCAACGGGCCGUGGUC;
  	or
  	(SEQ ID NO: 3082)
  	GGAGCUCUAAUCCCCACGCC.

• In an embodiment, when the SCD 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, the targeting domain of each guide RNA is selected from one of Table 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 Table 5A-5E. In an embodiment, the targeting domain is selected from those in Table 5A-5E.
• In an embodiment, when the SCD 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, the targeting domain of each guide RNA is selected from one of Table 5A-5E.
• 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 Table 6A-6B. In an embodiment, the targeting domain is selected from those in Table 6A-6B.
• In an embodiment, when the SCD 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, the targeting domain of each guide RNA is selected from one of Table 6A-6B.
• 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 Table 15A-15D. In an embodiment, the targeting domain is selected from those in Table 15A-15D.
• In an embodiment, when the SCD 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, the targeting domain of each guide RNA is selected from one of Table 15A-15D.
• 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 Table 16A-16E. In an embodiment, the targeting domain is selected from those in Table 16A-16E.
• In an embodiment, when the SCD 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, the targeting domain of each guide RNA is selected from one of Table 16A-16E.
• 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 Table 17A-17B. In an embodiment, the targeting domain is selected from those in Table 17A-17B.
• In an embodiment, when the SCD 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, the targeting domain of each guide RNA is selected from one of Table 17A-17B.
• 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 7A-7D. In an embodiment, the targeting domain is selected from those in Tables 7A-7D. In another embodiment, the targeting domain is:

• 	(SEQ ID NO: 4835)
  	GAAAAUACUUACUGUACUGC;
  	(SEQ ID NO: 4836)
  	GAAAGCAGUGUAAGGCU;
  	(SEQ ID NO: 4837)
  	GGCUGUUUUGGAAUGUAGAG;
  	or
  	(SEQ ID NO: 4838)
  	GUGCUACUUAUACAAUUCAC.

• In an embodiment, when the SCD target knockout position is the non-coding region, e.g., the enhancer region, of the BCL11A gene, 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 a deletion, in the target nucleic acid sequence, the targeting domain of each guide RNA is selected from one of Table 7A-7D.
• 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 8A-8D. In an embodiment, the targeting domain is selected from those in Tables 8A-8D.
• In an embodiment, when the SCD target knockout position is the non-coding region, e.g., the enhancer region, of the BCL11A gene, 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 a deletion, in the target nucleic acid sequence, the targeting domain of each guide RNA is selected from one of Table 8A-8D.
• 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 Table 9. In an embodiment, the targeting domain is selected from those in Table 9.
• In an embodiment, when the SCD target knockout position is the non-coding region, e.g., the enhancer region, of the BCL11A gene, 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 a deletion, in the target nucleic acid sequence, the targeting domain of each guide RNA is selected from one of Table 9.
• 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 21A-21E. In an embodiment, the targeting domain is selected from those in Tables 21A-21E. In an embodiment, when the SCD target knockout position is the non-coding region, e.g., the enhancer region, of the BCL11A gene, 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 a deletion, in the target nucleic acid sequence, the targeting domain of each guide RNA is selected from one of Table 21A-21E.
• 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 22A-22E. In an embodiment, the targeting domain is selected from those in Tables 22A-22E. In an embodiment, when the SCD target knockout position is the non-coding region, e.g., the enhancer region, of the BCL11A gene, 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 a deletion, in the target nucleic acid sequence, the targeting domain of each guide RNA is selected from one of Table 22A-22E.
• 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 23A-23C. In an embodiment, the targeting domain is selected from those in Tables 23A-23C.
• In an embodiment, when the SCD target knockout position is the non-coding region, e.g., the enhancer region, of the BCL11A gene, 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 a deletion, in the target nucleic acid sequence, the targeting domain of each guide RNA is selected from one of Table 23A-23C.
• In an embodiment, the targeting domain of the gRNA molecule is 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 an SCD knockdown target position to reduce, decrease or repress expression of the BCL11A gene. In an embodiment, the targeting domain is configured to target the promoter region of the BCL11A gene to block transcription initiation, binding of one or more transcription enhancers or activators, and/or RNA polymerase. One or more gRNA may be used to target an eiCas9 to the promoter region of the BCL11A gene.
• 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 3A-3C. In an embodiment, the targeting domain is selected from those in Tables 3A-3C.
• In an embodiment, when the SCD target knockdown position is the BCL11A promoter region and more than one gRNA is used to position an eiCas9 or an eiCas9-fusion protein (e.g., an eiCas9-transcription repressor domain fusion protein), in the target nucleic acid sequence, the targeting domain of each guide RNA is selected from one of Tables 3A-3C.
• 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 selected from those in Tables 10A-10D. In another embodiment, the targeting domain is:

• 	(SEQ ID NO: 4981)
  	GACGACGGCUCGGUUCACAU;
  	(SEQ ID NO: 4982)
  	GACGCCAGACGCGGCCCCCG;
  	(SEQ ID NO: 4983)
  	GCCUUGCUUGCGGCGAGACA;
  	(SEQ ID NO: 4984)
  	GGCUCCGCGGACGCCAGACG;
  	(SEQ ID NO: 4985)
  	GACGGCUCGGUUCACAU;
  	(SEQ ID NO: 4986)
  	GCCGCGUCUGGCGUCCG;
  	or
  	(SEQ ID NO: 4987)
  	GCGGGCGGACGACGGCU.

• In an embodiment, when the SCD target knockdown position is the BCL11A promoter region and more than one gRNA is used to position an eiCas9 or an eiCas9-fusion protein (e.g., an eiCas9-transcription repressor domain fusion protein), in the target nucleic acid sequence, each guide RNA is selected from one of 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 Tables 11A-11D. In an embodiment, the targeting domain is selected from those in Tables 11A-11D.
• In an embodiment, when the SCD target knockdown position is the BCL11A promoter region and more than one gRNA is used to position an eiCas9 or an eiCas9-fusion protein (e.g., an eiCas9-transcription repressor domain fusion protein), in the target nucleic acid sequence, each guide RNA is selected from one of Tables 11A-11D.
• 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 Table 12. In an embodiment, the targeting domain is selected from those in Table 12.
• In an embodiment, when the SCD target knockdown position is the BCL11A promoter region and more than one gRNA is used to position an eiCas9 or an eiCas9-fusion protein (e.g., an eiCas9-transcription repressor domain fusion protein), in the target nucleic acid sequence, each guide RNA is selected from Table 12.
• 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 18A-18C. In an embodiment, the targeting domain is selected from those in Tables 18A-18C.
• In an embodiment, when the SCD target knockdown position is the BCL11A promoter region and more than one gRNA is used to position an eiCas9 or an eiCas9-fusion protein (e.g., an eiCas9-transcription repressor domain fusion protein), in the target nucleic acid sequence, each guide RNA is selected from one of Tables 18A-18C.
• 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 19A-19E. In an embodiment, the targeting domain is selected from those in Tables 19A-19E.
• In an embodiment, when the SCD target knockdown position is the BCL11A promoter region and more than one gRNA is used to position an eiCas9 or an eiCas9-fusion protein (e.g., an eiCas9-transcription repressor domain fusion protein), in the target nucleic acid sequence, each guide RNA is selected from one of Tables 19A-19E.
• 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 20A-20C. In an embodiment, the targeting domain is selected from those in Tables 20A-20C.
• In an embodiment, when the SCD target knockdown position is the BCL11A promoter region and more than one gRNA is used to position an eiCas9 or an eiCas9-fusion protein (e.g., an eiCas9-transcription repressor domain fusion protein), in the target nucleic acid sequence, each guide RNA is selected from one of Tables 20A-20C.
• 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 selected from any one of Tables 1A-1D, 2A-2F, 3A-3C, 4A-4E, 5A-5E, 6A-6B, 7A-7D, 8A-8D, 9, 10A-10D, 11A-11D, 12, 13A-13D, 14A-14C, 15A-15D, 16A-16E, 17A-17B, 18A-18C, 19A-19E, 20A-20C, 21A-21E, 22A-22E, 23A-23C, 24A-24D, 25A-25B, 26, or 31. In an embodiment, the targeting domain is selected from those in Tables 1A-1D, 2A-2F, 3A-3C, 4A-4E, 5A-5E, 6A-6B, 7A-7D, 8A-8D, 9, 10A-10D, 11A-11D, 12, 13A-13D, 14A-14C, 15A-15D, 16A-16E, 17A-17B, 18A-18C, 19A-19E, 20A-20C, 21A-21E, 22A-22E, 23A-23C, 24A-24D, 25A-25B, 26, or 31.
• In an embodiment, the targeting domain which is complementary with the BCL11A 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 the HBB gene or BCL11A gene, is a modular gRNA. In another embodiment, the gRNA is a unimolecular or chimeric gRNA.
• HBB 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 Krüppel-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 an SCD target position, in the HBB gene or 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 an SCD target position in the HBB gene or BCL11A gene to allow alteration, e.g., alteration associated with HDR or NHEJ, of the an SCD target position in the HBB gene or 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) or an eiCas9 fusion protein (e.g., an eiCas9 fused to a transcription repressor domain), sufficiently close to an SCD 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-1D, 2A-2F, 3A-3C, 4A-4E, 5A-5E, 6A-6B, 7A-7D, 8A-8D, 9, 10A-10D, 11A-11D, 12, 13A-13D, 14A-14C, 15A-15D, 16A-16E, 17A-17B, 18A-18C, 19A-19E, 20A-20C, 21A-21E, 22A-22E, 23A-23C, 24A-24D, 25A-25B, 26, or 31. In an embodiment, the nucleic acid encodes a gRNA molecule comprising a targeting domain is selected from those in Tables 1A-1D, 2A-2F, 3A-3C, 4A-4E, 5A-5E, 6A-6B, 7A-7D, 8A-8D, 9, 10A-10D, 11A-11D, 12, 13A-13D, 14A-14C, 15A-15D, 16A-16E, 17A-17B, 18A-18C, 19A-19E, 20A-20C, 21A-21E, 22A-22E, 23A-23C, 24A-24D, 25A-25B, 26, 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 one 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 30 nucleotides in length; and a targeting domain equal to or greater than 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or 26 nucleotides in length.
• In an embodiment, a nucleic acid encodes a gRNA e.g., the first gRNA molecule, comprising a linking domain of no more than 25 nucleotides in length; a proximal and tail domain, that taken together, are at least 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 HBB gene or 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 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 Krüppel-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 HBB gene or BCL11A gene as disclosed herein; (b) a sequence that encodes a Cas9 molecule; and further comprises (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 HBB gene or 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 HBB gene or 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 HBB gene or BCL11A 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 an SCD target position in the HBB gene or BCL11A gene, to allow alteration, e.g., alteration associated with HDR or NHEJ, of an SCD target position in the HBB gene or BCL11A 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) or an eiCas9 fusion protein (e.g., an eiCas9 fused to a transcription repressor domain), sufficiently close to an SCD knockdown target position to reduce, decrease or repress expression of the BCL11A 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 an SCD target position in the HBB gene or BCL11A gene to allow alteration, e.g., alteration associated with HDR or NHEJ, of an SCD target position in the HBB gene or BCL11A 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) or an eiCas9 fusion protein (e.g., an eiCas9 fused to a transcription repressor domain), sufficiently close to an SCD knockdown target position to reduce, decrease or repress expression of the BCL11A 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 an SCD target position in the HBB gene or BCL11A gene to allow alteration, e.g., alteration associated with HDR or NHEJ, of an SCD target position in the HBB gene or BCL11A 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 an SCD 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 SCD 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 SCD target position as the first and/or 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-1D, 2A-2F, 3A-3C, 4A-4E, 5A-5E, 6A-6B, 7A-7D, 8A-8D, 9, 10A-10D, 11A-11D, 12, 13A-13D, 14A-14C, 15A-15D, 16A-16E, 17A-17B, 18A-18C, 19A-19E, 20A-20C, 21A-21E, 22A-22E, 23A-23C, 24A-24D, 25A-25B, 26, or 31. In an embodiment, the nucleic acid encodes a second gRNA molecule comprising a targeting domain selected from those in Tables 1A-1D, 2A-2F, 3A-3C, 4A-4E, 5A-5E, 6A-6B, 7A-7D, 8A-8D, 9, 10A-10D, 11A-11D, 12, 13A-13D, 14A-14C, 15A-15D, 16A-16E, 17A-17B, 18A-18C, 19A-19E, 20A-20C, 21A-21E, 22A-22E, 23A-23C, 24A-24D, 25A-25B, 26, 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-1D, 2A-2F, 3A-3C, 4A-4E, 5A-5E, 6A-6B, 7A-7D, 8A-8D, 9, 10A-10D, 11A-11D, 12, 13A-13D, 14A-14C, 15A-15D, 16A-16E, 17A-17B, 18A-18C, 19A-19E, 20A-20C, 21A-21E, 22A-22E, 23A-23C, 24A-24D, 25A-25B, 26, 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-1D, 2A-2F, 3A-3C, 4A-4E, 5A-5E, 6A-6B, 7A-7D, 8A-8D, 9, 10A-10D, 11A-11D, 12, 13A-13D, 14A-14C, 15A-15D, 16A-16E, 17A-17B, 18A-18C, 19A-19E, 20A-20C, 21A-21E, 22A-22E, 23A-23C, 24A-24D, 25A-25B, 26, 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/or 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 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 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, when the HBB gene is corrected, e.g., by HDR, the nucleic acid encodes (a) a sequence that encodes a gRNA molecule comprising a targeting domain that is complementary with a target domain in the HBB gene as disclosed herein; (b) a sequence that encodes a Cas9 molecule; optionally, (c)(i) a sequence that encodes a second gRNA molecule described herein having a targeting domain that is complementary to a second target domain of the HBB gene, and further optionally, (c)(ii) a sequence that encodes a third gRNA molecule described herein having a targeting domain that is complementary to a third target domain of the HBB gene; and still further optionally, (c)(iii) a sequence that encodes a fourth gRNA molecule described herein having a targeting domain that is complementary to a fourth target domain of the HBB gene; and further may comprise (d) a template nucleic acid (in an embodiment where an exogenous template is used).
• In an embodiment, a mutation in the HBB gene is corrected, e.g., by HDR, using an exogenously provided template nucleic acid.
• In an embodiment, the template nucleic acid is a single stranded nucleic acid. In another embodiment, the template nucleic acid is a double stranded nucleic acid. In an embodiment, the template nucleic acid comprises a nucleotide sequence, e.g., of one or more nucleotides, that will be added to or will template a change in the target nucleic acid. In another embodiment, the template nucleic acid comprises a nucleotide sequence that may be used to modify the target position. In another embodiment, the template nucleic acid comprises a nucleotide sequence, e.g., of one or more nucleotides, that corresponds to wild type sequence of the target nucleic acid, e.g., of the target position.
• The template nucleic acid may comprise a replacement sequence, e.g., a replacement sequence from the Table 27. In an embodiment, the template nucleic acid comprises a 5′ homology arm, e.g., a 5′ homology arm from Table 27. In another embodiment, the template nucleic acid comprises a 3′ homology arm, e.g., a 3′ homology arm from Table 27.
• In another embodiment, a mutation in the HBB gene is corrected, e.g., by HDR, without using an exogenously provided template nucleic acid. While not wishing to be bound by theory, it is believed that an endogenous region of homology can mediate HDR-based correction. In an embodiment, alteration of the target sequence occurs by HDR with an endogenous genomic donor sequence. In an embodiment, the endogenous genomic donor sequence is located on the same chromosome as the target sequence. In another embodiment, the endogenous genomic donor sequence is located on a different chromosome from the target sequence. In an embodiment, the endogenous genomic donor sequence comprises one or more nucleotides derived from the HBD gene. Mutations in the HBB gene that can be corrected (e.g., altered) by HDR with an endogenous genomic donor sequence include, e.g., a point mutation at E6, e.g., E6V.
• As described above, a nucleic acid may comprise (a) a sequence encoding a gRNA molecule comprising a targeting domain that is complementary with a target domain in the HBB gene or BCL11A gene, and (b) a sequence encoding a Cas9 molecule.
• 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, the nucleic acid may further comprise (c) a sequence that encodes a second, third and/or fourth gRNA molecule as described herein. In an embodiment, the nucleic acid comprises (a), (b) and (c). Each of (a) and (c) 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) 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) 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) 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) 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) 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) 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) 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) 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) 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) 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 further embodiments, each of (a), (b), (c)(i), (c)(ii) and (c)(iii) may be present on more than one nucleic acid molecule, but fewer than five nucleic acid molecules, e.g., AAV vectors.
• In another embodiment, when (d) a template nucleic acid is present, each of (a), (b), and (d) may be present on the same nucleic acid molecule, e.g., the same vector, e.g., the same viral vector, e.g., an AAV vector. In an embodiment, the nucleic acid molecule is an AAV vector. In an alternate embodiment, each of (a), (b), and (d) may be present on the different nucleic acid molecules, e.g., different vectors, e.g., the different viral vectors, e.g., different AAV vectors. In further embodiments, each of (a), (b), and (d) may be present on more than one nucleic acid molecule, but fewer than three nucleic acid molecules, e.g., AAV vectors.
• In another embodiment, when (d) a template nucleic acid is present, each of (a), (b), (c)(i) and (d) may be present on the same nucleic acid molecule, e.g., the same vector, e.g., the same viral vector, e.g., an AAV vector. In an embodiment, the nucleic acid molecule is an AAV vector. In an alternate embodiment, each of (a), (b), (c)(i) and (d) may be present on the different nucleic acid molecules, e.g., different vectors, e.g., the different viral vectors, e.g., different AAV vectors. In further embodiments, each of (a), (b), (c)(i) and (d) may be present on more than one nucleic acid molecule, but fewer than four nucleic acid molecules, e.g., AAV vectors.
• In another embodiment, when (d) a template nucleic acid is present, each of (a), (b), (c)(i), (c)(ii) and (d) may be present on the same nucleic acid molecule, e.g., the same vector, e.g., the same viral vector, e.g., an AAV vector. In an embodiment, the nucleic acid molecule is an AAV vector. In an alternate embodiment, each of (a), (b), (c)(i), (c)(ii) and (d) may be present on the different nucleic acid molecules, e.g., different vectors, e.g., the different viral vectors, e.g., different AAV vectors. In further embodiments, each of (a), (b), (c)(i), (c)(ii) and (d) may be present on more than one nucleic acid molecule, but fewer than five nucleic acid molecules, e.g., AAV vectors.
• In another embodiment, when (d) a template nucleic acid is present, each of (a), (b), (c)(i), (c)(ii), (c)(iii) and (d) may be present on the same nucleic acid molecule, e.g., the same vector, e.g., the same viral vector, e.g., an AAV vector. In an embodiment, the nucleic acid molecule is an AAV vector. In an alternate embodiment, each of (a), (b), (c)(i), (c)(ii), (c)(iii) and (d) may be present on the different nucleic acid molecules, e.g., different vectors, e.g., the different viral vectors, e.g., different AAV vectors. In further embodiments, each of (a), (b), (c)(i), (c)(ii), (c)(iii) and (d) may be present on more than one nucleic acid molecule, but fewer than six nucleic acid molecules, e.g., AAV vectors.
• The nucleic acids described herein may comprise a promoter operably linked to the sequence that encodes the gRNA molecule of (a), e.g., a promoter described herein. The nucleic acid may further comprise a second promoter operably linked to the sequence that encodes the second, third and/or fourth gRNA molecule of (c), e.g., a promoter described herein. The promoter and second promoter differ from one another. In 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 HBB gene or BCL11A gene, as described herein. The composition of (a) may further comprise (b) a Cas9 molecule, e.g., a Cas9 molecule as described herein. A composition of (a) and (b) may further comprise (c) a second, third and/or fourth gRNA molecule, e.g., a second, third and/or fourth gRNA molecule described herein. A composition of (a), (b) and (c) may further comprise (d) a template nucleic acid (in an embodiment where an exogenous template is used). In an embodiment, the composition is a pharmaceutical composition. The Compositions described herein, e.g., pharmaceutical compositions described herein, can be used in treating SCD 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 HBB gene or BCL11A 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 HBB gene or BCL11A gene, e.g., a gRNA; and optionally, (d) a template nucleic acid, as described herein.
• In an embodiment, the method comprises contacting said cell with (a) and (b).
• In an embodiment, the method comprises contacting said cell with (a), (b), and (c).
• In an embodiment, the method comprises contacting said cell with (a), (b), (c) and (d).
• In an embodiment, the gRNA targets the HBB gene and no exogenous template nucleic acid is contacted with the cell.
• The gRNA of (a) and optionally (c) may be selected from any of Tables 1A-1D, 2A-2F, 3A-3C, 4A-4E, 5A-5E, 6A-6B, 7A-7D, 8A-8D, 9, 10A-10D, 11A-11D, 12, 13A-13D, 14A-14C, 15A-15D, 16A-16E, 17A-17B, 18A-18C, 19A-19E, 20A-20C, 21A-21E, 22A-22E, 23A-23C, 24A-24D, 25A-25B, 26, or 31, or a gRNA that differs by no more than 1, 2, 3, 4, or 5 nucleotides from, a targeting domain sequence from any of Tables 1A-1D, 2A-2F, 3A-3C, 4A-4E, 5A-5E, 6A-6B, 7A-7D, 8A-8D, 9, 10A-10D, 11A-11D, 12, 13A-13D, 14A-14C, 15A-15D, 16A-16E, 17A-17B, 18A-18C, 19A-19E, 20A-20C, 21A-21E, 22A-22E, 23A-23C, 24A-24D, 25A-25B, 26, or 31.
• In an embodiment, the method comprises contacting a cell from a subject suffering from or likely to develop SCD. The cell may be from a subject having a mutation at an SCD target position in the HBB gene or a subject which would benefit from having a mutation at an SCD target position in the BCL11A gene.
• 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 at an SCD target position in said cell, prior to the contacting step. Acquiring knowledge of the sequence at an SCD target position in the cell may be by sequencing the HBB gene or BCL11A gene, or a portion of the HBB gene or 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), (c) and (d). In an embodiment, the contacting step of the method comprises contacting the cell with a nucleic acid, e.g., a vector, e.g., an AAV vector, that expresses each of (a), (b), and (c). In another embodiment, the contacting step of the method comprises delivering to the cell a Cas9 molecule of (b), a nucleic acid which encodes a gRNA of (a) and a template nucleic acid of (d), and optionally, a second gRNA (c)(i) (and further optionally, a third gRNA (c)(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.
• 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) 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 or preventing a subject suffering from or likely to develop SCD, 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 HBB gene or BCL11A 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 HBB gene or BCL11A 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 HBB gene or BCL11A gene, e.g., a third and fourth gRNA disclosed herein.
• The method of treating a subject may further comprise contacting the subject (or a cell from the subject) with (d) a template nucleic acid (in an embodiment where an exogenous template is used), e.g., a template nucleic acid disclosed herein.
• In an embodiment, a template nucleic acid is used when the method of treating a subject uses HDR to alter the sequence of the target nucleic acid of the subject. In an embodiment, the gRNA targets the HBB gene and no exogenous template nucleic acid is contacted with the subject (or a cell from the subject).
• 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).
• In an embodiment, contacting comprises contacting with (a), (b), (c)(i) and (d).
• In an embodiment, contacting comprises contacting with (a), (b), (c)(i), (c)(ii) and (d).
• In an embodiment, contacting comprises contacting with (a), (b), (c)(i), (c)(ii), (c)(iii) and (d).
• The gRNA of (a) or (c) (e.g., (c)(i), (c)(ii), or (c)(iii) may be selected from any of Tables 1A-1D, 2A-2F, 3A-3C, 4A-4E, 5A-5E, 6A-6B, 7A-7D, 8A-8D, 9, 10A-10D, 11A-11D, 12, 13A-13D, 14A-14C, 15A-15D, 16A-16E, 17A-17B, 18A-18C, 19A-19E, 20A-20C, 21A-21E, 22A-22E, 23A-23C, 24A-24D, 25A-25B, 26, or 31, or a gRNA that differs by no more than 1, 2, 3, 4, or 5 nucleotides from, a targeting domain sequence from any of Tables 1A-1D, 2A-2F, 3A-3C, 4A-4E, 5A-5E, 6A-6B, 7A-7D, 8A-8D, 9, 10A-10D, 11A-11D, 12, 13A-13D, 14A-14C, 15A-15D, 16A-16E, 17A-17B, 18A-18C, 19A-19E, 20A-20C, 21A-21E, 22A-22E, 23A-23C, 24A-24D, 25A-25B, 26, or 31.
• In an embodiment, the method comprises acquiring knowledge of the sequence (e.g., a mutation) of an SCD target position in said subject.
• In an embodiment, the method comprises acquiring knowledge of the sequence (e.g., a mutation) of an SCD target position in said subject by sequencing the HBB gene or BCL11A gene or a portion of the HBB gene or BCL11A gene.
• In an embodiment, the method comprises correcting a mutation at an SCD target position in the HBB gene.
• In an embodiment, the method comprises correcting a mutation at an SCD target position in the HBB gene by HDR.
• In an embodiment, the method comprises introducing a mutation at an SCD target position in the BCL11A gene.
• In an embodiment, the method comprises introducing a mutation at an SCD target position in the BCL11A gene by NHEJ.
• When the method comprises correcting the mutation at an SCD target position by HDR, a Cas9 of (b), at least one guide RNA, e.g., a guide RNA of (a) and a template nucleic acid of (d) are included in the contacting step.
• In an embodiment, a cell of the subject is contacted ex vivo with (a), (b), (d) and optionally (c)(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) (d) and optionally (c)(i), further optionally (c)(ii), and still further optionally (c)(iii).
• In an embodiment, the cell of the subject is contacted in vivo by intravenous delivery of (a), (b), (d) and optionally (c)(i), further optionally (c)(ii), and still further optionally (c)(iii).
• In an embodiment, the cell of the subject is contacted in vivo by intramuscular delivery of (a), (b), (d) and optionally (c)(i), further optionally (c)(ii), and still further optionally (c)(iii).
• In an embodiment, the cell of the subject is contacted in vivo by subcutaneous delivery of (a), (b), (d) and optionally (c)(i), further optionally (c)(ii), and still further optionally (c)(iii).
• In an embodiment, the cell of the subject is contacted in vivo by intra-bone marrow (IBM) delivery of (a), (b), (d) and optionally (c)(i), further optionally (c)(ii), and still further optionally (c)(iii).
• In an embodiment, contacting comprises contacting the subject with a nucleic acid, e.g., a vector, e.g., an AAV vector, described herein, e.g., a nucleic acid that encodes at least one of (a), (b), (d) and optionally (c)(i), further optionally (c)(ii), and still further optionally (c)(iii).
• In an embodiment, contacting comprises delivering to said subject said Cas9 molecule of (b), as a protein or mRNA, and a nucleic acid which encodes (a), a nucleic acid of (d) and optionally (c)(i), further optionally (c)(ii), and still further optionally (c)(iii).
• In an embodiment, contacting comprises delivering to the subject the Cas9 molecule of (b), as a protein or mRNA, the gRNA of (a), as an RNA, a nucleic acid of (d) and optionally the second, third and/or fourth gRNA of (c), as an RNA.
• In an embodiment, contacting comprises delivering to the subject the gRNA of (a), as an RNA, optionally said second, third and/or fourth gRNA of (c), as an RNA, a nucleic acid that encodes the Cas9 molecule of (b), and a nucleic acid of (d).
• When the method comprises (1) introducing a mutation at an SCD target position by NHEJ or (2) knocking down expression of the BCL11A gene by targeting the promoter region, a Cas9 of (b) and at least one guide RNA, e.g., a guide RNA of (a) are included in the contacting step.
• In an embodiment, a cell of the subject is contacted ex vivo with (a), (b) and optionally (c)(i), further optionally (c)(ii), and still further optionally (c)(iii). In an embodiment, said cell is returned to the subject's body.
• In an embodiment, a populations of cells from a subject is contacted ex vivo with (a), (b) and optionally (c) to correct the E6V mutation in the HBB gene and a second population of cells from the subject is contacted ex vivo with (a), (b) and optionally (c) to introduce a mutation in the BCL11A gene to knockout the BCL11A gene. A mixture of the two cell populations may be returned to the subject's body to treat or prevent SCD.
• 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 cell of the subject is contacted in vivo by intramuscular delivery of (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 subcutaneous delivery of (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 intra-bone marrow (IBM) delivery of (a), (b) and optionally (c)(i), further optionally (c)(ii), and still further optionally (c)(iii).
• In an embodiment, contacting comprises contacting the subject with a nucleic acid, e.g., a vector, e.g., an AAV vector, described herein, e.g., a nucleic acid that encodes at least one of (a), (b), and optionally (c)(i), further optionally (c)(ii), and still further optionally (c)(iii).
• In an embodiment, contacting comprises delivering to said subject said Cas9 molecule of (b), as a protein or mRNA, and a nucleic acid which encodes (a) and optionally (c)(i), further optionally (c)(ii), and still further optionally (c)(iii).
• In an embodiment, contacting comprises delivering to the subject the Cas9 molecule of (b), as a protein or mRNA, the gRNA of (a), as an RNA, and optionally the second, third and/or fourth gRNA of (c), as an RNA.
• In an embodiment, contacting comprises delivering to the subject the 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 reaction mixture comprising a gRNA, a nucleic acid, or a composition described herein, and a cell, e.g., a cell from a subject having, or likely to develop SCD, or a subject having a mutation at an SCD target position in the HBB gene, or a cell from a subject which would benefit from having a mutation at an SCD target position in the BCL11A gene.
• In another aspect, disclosed herein is a kit comprising, (a) gRNA molecule described herein, or nucleic acid that encodes the gRNA, and one or more of the following:
• (b) a Cas9 molecule, e.g., a Cas9 molecule described herein, or a nucleic acid or mRNA that encodes the Cas9;
• (c)(i) a second gRNA molecule, e.g., a second gRNA molecule described herein or a nucleic acid that encodes (c)(i);
• (c)(ii) a third gRNA molecule, e.g., a second gRNA molecule described herein or a nucleic acid that encodes (c)(ii);
• (c)(iii) a fourth gRNA molecule, e.g., a second gRNA molecule described herein or a nucleic acid that encodes (c)(iii);
• (d) a template nucleic acid (in an embodiment where an exogenous template is used), e.g., a template nucleic acid described herein.
• In an embodiment, the kit comprises nucleic acid, e.g., an AAV vector, that encodes one or more of (a), (b), (c)(i), (c)(ii), (c)(iii) and (d).
• In 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 compositions, reaction mixtures and kits, as disclosed herein, can also include a governing gRNA molecule, e.g., a governing gRNA molecule disclosed herein.
• Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, suitable methods and materials are described below. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting.
• Headings, including numeric and alphabetical headings and subheadings, are for organization and presentation and are not intended to be limiting.
• Other features and advantages of the invention will be apparent from the detailed description, drawings, and from the claims.
BRIEF DESCRIPTION OF THE DRAWINGS
• FIGS. 1A-1I are representations of several exemplary gRNAs.
• FIG. 1A depicts a modular gRNA molecule derived in part (or modeled on a sequence in part) from Streptococcus pyogenes (S. pyogenes) as a duplexed structure (SEQ ID NOS: 42 and 43, respectively, in order of appearance);
• FIG. 1B 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. 1D depicts a unimolecular gRNA molecule derived in part from S. pyogenes as a duplexed structure (SEQ ID NO: 46);
• FIG. 1E depicts a unimolecular gRNA molecule derived in part from S. pyogenes as a duplexed structure (SEQ ID NO: 47);
• FIG. 1F 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. 11 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 BCL11A intron 2. Three erythroid DHSs are labeled as distance in kilobases from BCL11A TSS (+62, +58 and +55). BCL11A 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 BCL11A locus.
• FIGS. 12A-12B depict detected deletion events resulting from co-transfection of exemplary gRNA molecules, BCL11A-2983W and BCL11A-2981W.
• FIG. 12A depicts schematic of DNA sequence recognized by BCL11A-2983W and BCL11A-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 depicts 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 BCL11A-2995W and BCL11A-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.
• FIG. 14 depicts a scheme of the pair 8/15 of gRNAs surrounding the sickle mutation in combination with a Cas9 nickase (D10A or N863A). The nickases are shown as the grey ovals.
• FIG. 15 depicts the percentages of total editing event after a wildtype Cas9 or a Cas9 nickase (D10A or N863A). A preprentation of at least three independent experiments for each condition is shown.
• FIG. 16A depicts the frequency of deletions a wildtype Cas9 or a Cas9 nickase (D10A or N863A). A representation of at least 3 independent experiments for each condition is shown.
• FIG. 16B depicts the frequency distribution of the length of deletions using a wildtype Cas9 and gRNA 8 (similar results have been obtained with gRNA 15).
• FIG. 16C depicts the frequency distribution of the length of deletions using a Cas9 nickase (D10A) with gRNAs 8/15 (similar results have been obtained using Cas9 N863A).
• FIG. 17A depicts the frequency of gene conversion a wildtype Cas9 or a Cas9 nickase (D10A or N863A).
• FIG. 17B shows a scheme representing the region of similarity between the HBB and HBD loci.
• FIG. 18 depicts the frequency of different lengths of HBD sequences that were incorporated into the HBB locus.
• FIG. 19A depicts the frequency of insertions using a wildtype Cas9 or a Cas9 nickase (D10A or N863A). A representation of at least three independent experiments for each condition is shown.
• FIG. 19B depicts examples of common reads observed in U2OS cells electroporated with plasmid encoding Cas9 N863 and gRNA 8/15 pair. The HBB reference is shown on the top.
• FIG. 20A is a schematic representation of the donor template.
• FIG. 20B depicts the frequency of HDR using a wildtype Cas9 or a Cas9 nickase (D10A or N863A).
• FIG. 20C depicts different forms of nonors and there contribution to HDR.
• FIG. 21 depicts genome editing of the HBB locus in bone marrow leukemia K562 hematopoietic cells after electroporation of Cas9 protein complexed to HBB gRNAs 8 and 15 (RNP) or Cas9 mRNA co-delivered with HBB gRNAs 8 and 15 (RNA).
DETAILED DESCRIPTION Definitions
• “Alt-HDR” or “alternative HDR”, or alternative homology-directed repair, as used herein, refers to the process of repairing DNA damage using a homologous nucleic acid (e.g., an endogenous homologous sequence, e.g., a sister chromatid, or an exogenous nucleic acid, e.g., a template nucleic acid). Alt-HDR is distinct from canonical HDR in that the process utilizes different pathways from canonical HDR, and can be inhibited by the canonical HDR mediators, RAD51 and BRCA2. Also, alt-HDR uses a single-stranded or nicked homologous nucleic acid for repair of the break.
• “Canonical HDR”, or canonical homology-directed repair, as used herein, refers to the process of repairing DNA damage using a homologous nucleic acid (e.g., an endogenous homologous sequence, e.g., a sister chromatid, or an exogenous nucleic acid, e.g., a template nucleic acid). Canonical HDR typically acts when there has been significant resection at the double strand break, forming at least one single stranded portion of DNA. In a normal cell, HDR typically involves a series of steps such as recognition of the break, stabilization of the break, resection, stabilization of single stranded DNA, formation of a DNA crossover intermediate, resolution of the crossover intermediate, and ligation. The process requires RAD51 and BRCA2, and the homologous nucleic acid is typically double-stranded.
• Unless indicated otherwise, the term “HDR” as used herein encompasses canonical HDR and alt-HDR.
• “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 HBB or 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). 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 HBB or BCL11A 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, biologics, 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 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 Repairing Mutation(s) in the HBB Gene
• One approach to treat or prevent SCD is to repair (i.e., correct) one or more mutations in the HBB gene, e.g., by HDR. In this approach, mutant HBB allele(s) are corrected and restored to wild type state. While not wishing to be bound by theory, it is believed that correction of the glutamic acid to valine substitution at amino acid 6 in the beta-globin gene restores wild type beta-globin production within erythroid cells. The method described herein can be performed in all cell types. Beta-globin is expressed in cells of erythroid cell lineage. In an embodiment, an erythroid cell is targeted.
• In an embodiment, one HBB allele is repaired in the subject. In another embodiment, both HBB alleles are repaired in the subject. In either situation, the subject can be cured of disease. As the disease only displays a phenotype when both alleles are mutated, repair of a single allele is adequate for a cure.
• In one aspect, methods and compositions discussed herein, provide for the correction of the underlying genetic cause of SCD, e.g., the correction of a mutation at a target position in the HBB gene, e.g., correction of a mutation at amino acid position 6, e.g., an E6V substitution in the HBB gene.
• In an embodiment, the method provides for the correction of a mutation at a target position in the HBB gene, e.g., correction of a mutation at amino acid position 6, e.g., an E6V substitution in the HBB 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 target position in the HBB gene, e.g., E6V.
• In an embodiment, the targeting domain of the gRNA molecule is configured to provide a cleavage event, e.g., a double strand break or a single strand break, sufficiently close to (e.g., either 5′ or 3′ to) the target position in the HBB gene, e.g., E6V to allow correction, e.g., an alteration in the HBB gene, e.g., an alternation associated with HDR. In an embodiment, the targeting domain is configured such that a cleavage event, e.g., a double strand or single strand break, is positioned within 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450 or 500 nucleotides of a the target position in the HBB gene, e.g., E6V. The break, e.g., a double strand or single strand break, can be positioned upstream or downstream of the target position in the HBB gene, e.g., E6V.
• In an embodiment, a second, third and/or fourth gRNA molecule is configured to provide a cleavage event, e.g., a double strand break or a single strand break, sufficiently close to (e.g., either 5′ or 3′ to) the target position in the HBB gene, e.g., E6V to allow correction, e.g., an alteration associated with HDR in the HBB 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 the target position in the HBB gene, e.g., E6V. The break, e.g., a double strand or single strand break, can be positioned upstream or downstream of the target position in the HBB gene, e.g., E6V.
• In an embodiment, a single strand break is accompanied by an additional single strand break, positioned by a second, third and/or fourth gRNA molecule, as discussed below. For example, The targeting domains bind configured such that a cleavage event, e.g., the two single strand breaks, are positioned within 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450 or 500 nucleotides of the target position in the HBB gene, e.g., E6V. In an embodiment, the first and second gRNA molecules are configured such, that when guiding a Cas9 nickase, a single strand break will be accompanied by an additional single strand break, positioned by a second gRNA, sufficiently close to one another to result in an alteration of the target position in the HBB gene, e.g., E6V. In an embodiment, the first and second gRNA molecules are configured such that a single strand break positioned by said second gRNA is within 10, 20, 30, 40, or 50 nucleotides of the break positioned by said first gRNA molecule, e.g., when the Cas9 is a nickase. In an embodiment, the two gRNA molecules are configured to position cuts at the same position, or within a few nucleotides of one another, on different strands, e.g., essentially mimicking a double strand break.
• In an embodiment, a double strand break can be accompanied by an additional double strand break, positioned by a second, third and/or fourth gRNA molecule, as is discussed below. For example, the targeting domain of a first gRNA molecule is configured such that a double strand break is positioned upstream of the target position in the HBB gene, e.g., E6V, e.g., within 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450 or 500 nucleotides of the target position; and the targeting domain of a second gRNA molecule is configured such that a double strand break is positioned downstream the target position in the HBB gene, e.g., E6V, e.g., within 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450 or 500 nucleotides of the target position.
• In an embodiment, a double strand break can be accompanied by two additional single strand breaks, positioned by a second gRNA molecule and a third gRNA molecule. For example, the targeting domain of a first gRNA molecule is configured such that a double strand break is positioned upstream of the target position in the HBB gene, e.g., E6V, e.g., within 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450 or 500 nucleotides of the target position; and the targeting domains of a second and third gRNA molecule are configured such that two single strand breaks are positioned downstream of the target position in the HBB gene, e.g., E6V, e.g., within 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450 or 500 nucleotides of the target position. In an embodiment, the targeting domain of the first, second and third gRNA molecules are configured such that a cleavage event, e.g., a double strand or single strand break, is positioned, independently for each of the gRNA molecules.
• In an embodiment, a first and second single strand breaks can be accompanied by two additional single strand breaks positioned by a third gRNA molecule and a fourth gRNA molecule. For example, the targeting domain of a first and second gRNA molecule are configured such that two single strand breaks are positioned upstream of the target position in the HBB gene, e.g., E6V, e.g., within 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450 or 500 nucleotides of the target position in the HBB gene, e.g., E6V; and the targeting domains of a third and fourth gRNA molecule are configured such that two single strand breaks are positioned downstream of the target position in the HBB gene, e.g., E6V, e.g., within 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450 or 500 nucleotides of the target position in the HBB gene, e.g., E6V.
• In an embodiment, a mutation in the HBB gene, e.g., E6V is corrected using an exogenously provided template nucleic acid, e.g., by HDR. In another embodiment, a mutation in the HBB gene, e.g., E6V is corrected without using an exogenously provided template nucleic acid, e.g., by HDR. In an embodiment, alteration of the target sequence occurs with an endogenous genomic donor sequence, e.g., by HDR. In an embodiment, the endogenous genomic donor sequence comprises one or more nucleotides derived from the HBD gene. In an embodiment, a mutation in the HBB gene, e.g., E6V is corrected by an endogenous genomic donor sequence (e.g, an HBD gene). In an embodiment, an eaCas9 molecule, e.g., an eaCas9 molecule described herein, is used. 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 an embodiment, the eaCas9 molecule is an HNH-like domain nickase. In an embodiment, the eaCas9 molecule comprises a mutation at D10 (e.g., D10A). In an 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. In an embodiment, the eaCas9 molecule comprises a mutation at H840 (e.g., H840A) or N863 (e.g., N863A).
• 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. The BCL11A gene product is expressed in adult erythroid precursor cells and down-regulation of its expression leads to an increase in 7 globin expression. In addition, it appears that the splicing of the BCL11A mRNA is developmentally regulated. In embryonic cells, it appears that the shorter BCL11A mRNA variants, known as BCL11A-S and BCL11A-XS are primary expressed, while in adult cells, the longer BCL11A-L and BCL11A-XL mRNA variants are predominantly expressed. See, Sankaran et al (2008) Science 322 p. 1839. The BCL11A protein appears to interact with the β globin locus to alter its conformation and thus its expression at different developmental stages. Thus, if BCL11A 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 SCD target position in the BCL11A gene. Altering the SCD target position is achieved, e.g., by:
• (1) knocking out the BCL11A 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 BCL11A gene, or
  • (b) deletion (e.g., NHEJ-mediated deletion) of a genomic sequence including the erythroid enhancer of the BCL11A gene, or
• (2) knocking down the BCL11A 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 BCL11A gene.
• In one embodiment, methods described herein introduce one or more breaks near the early coding region in at least one allele of the BCL11A gene. In another embodiment, methods described herein introduce two or more breaks to flank the erythroid enhancer of SCD 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 BCL11A gene mediated by enzymatically inactive Cas9 (eiCas9) molecule or an eiCas9-fusion protein by targeting the promoter region of SCD target knockdown position. All methods described herein result in alteration of the BCL11A gene.
• NHEJ-Mediated Introduction of an Indel in Close Proximity to or within the Early Coding Region of the SCD Knockout Position
• In an embodiment, the method comprises introducing a NHEJ-mediated insertion or deletion of one more nucleotides in close proximity to the SCD 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 SCD target knockout position, such that the break-induced indel could be reasonably expected to span the SCD 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 SCD 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 SCD target knockout position. The break, e.g., a double strand or single strand break, can be positioned upstream or downstream of a SCD 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 SCD 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 SCD target knockout position in the BCL11A 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 bind configured such that a cleavage event, e.g., the two single strand breaks, are positioned within 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450 or 500 nucleotides of the early coding region in the BCL11A 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 BCL11A 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 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; 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 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, 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 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; 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 SCD target knockout position in 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 SCD 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 SCD 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 SCD 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 erythroid enhancer within intron 2 (e.g., between TSS+0.75 kb to TSS+52.0 kb), and the second double strand break is positioned downstream of the erythroid enhancer within intron 2 (e.g., between TSS+64.4 kb to TSS+84.7 kb) (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+0.75 kb to TSS+52.0 kb), 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+52.0 kb to TSS+64.4 kb), 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+64.4 kb to TSS+84.7 kb), 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+52.0 kb to TSS+64.4 kb).
• For example, the first double strand break may be positioned in the BCL11A gene:
• (1) between TSS+0.75 kb to TSS+10 kb,
• (2) between TSS+10 kb to TSS+20 kb,
• (3) between TSS+20 kb to TSS+30 kb,
• (4) between TSS+30 kb to TSS+40 kb,
• (5) between TSS+40 kb to TSS+45 kb,
• (6) between TSS+45 kb to TSS+47.5 kb,
• (7) between TSS+47.5 kb to TSS+50 kb,
• (8) between TSS+50 kb to TSS+51 kb,
• (9) between TSS+51 kb to TSS+51.1 kb,
• (10) between TSS+51.1 kb to TSS+51.2 kb,
• (11) between TSS+51.2 kb to TSS+51.3 kb,
• (12) between TSS+51.3 kb to TSS+51.4 kb,
• (13) between TSS+51.4 kb to TSS+51.5 kb,
• (14) between TSS+51.5 kb to TSS+51.6 kb,
• (15) between TSS+51.6 kb to TSS+51.7 kb,
• (16) between TSS+51.7 kb to TSS+51.8 kb,
• (17) between TSS+51.8 kb to TSS+51.9 kb,
• (18) between TSS+51.9 kb to TSS+52 kb,
• (19) between TSS+52 kb to TSS+53 kb,
• (20) between TSS+53 kb to TSS+54 kb,
• (21) between TSS+54 kb to TSS+55 kb,
• (22) between TSS+55 kb to TSS+56 kb,
• (23) between TSS+56 kb to TSS+57 kb,
• (24) between TSS+57 kb to TSS+58 kb,
• (25) between TSS+58 kb to TSS+59 kb,
• (26) between TSS+59 kb to TSS+60 kb,
• (27) between TSS+60 kb to TSS+61 kb,
• (28) between TSS+61 kb to TSS+62 kb,
• (29) between TSS+62 kb to TSS+63 kb,
• (30) between TSS+63 kb to TSS+64 kb, or
• (31) between TSS+64 kb to TSS+64.4 kb,
• 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+52 kb to TSS+53 kb,
• (2) between TSS+53 kb to TSS+54 kb,
• (3) between TSS+54 kb to TSS+55 kb,
• (4) between TSS+55 kb to TSS+56 kb,
• (5) between TSS+56 kb to TSS+57 kb,
• (6) between TSS+57 kb to TSS+58 kb,
• (7) between TSS+58 kb to TSS+59 kb,
• (8) between TSS+59 kb to TSS+60 kb,
• (9) between TSS+60 kb to TSS+61 kb,
• (10) between TSS+61 kb to TSS+62 kb,
• (11) between TSS+62 kb to TSS+63 kb,
• (12) between TSS+63 kb to TSS+64 kb,
• (13) between TSS+64 kb to TSS+64.4 kb,
• (14) between TSS+64.4 kb to TSS+65 kb,
• (15) between TSS+65 kb to TSS+65.1 kb,
• (16) between TSS+65.1 kb to TSS+65.2 kb,
• (17) between TSS+65.2 kb to TSS+65.3 kb,
• (18) between TSS+65.3 kb to TSS+65.4 kb,
• (19) between TSS+65.4 kb to TSS+65.5 kb,
• (20) between TSS+65.5 kb to TSS+65.7 kb,
• (21) between TSS+65.7 kb to TSS+65.8 kb,
• (22) between TSS+65.8 kb to TSS+65.9 kb,
• (23) between TSS+65.9 kb to TSS+66 kb,
• (24) between TSS+66 kb to TSS+67 kb,
• (25) between TSS+67 kb to TSS+68 kb,
• (26) between TSS+68 kb to TSS+69 kb,
• (27) between TSS+69 kb to TSS+70 kb,
• (28) between TSS+70 kb to TSS+75 kb,
• (29) between TSS+75 kb to TSS+80 kb, or
• (30) between TSS+80 kb to TSS+84.4 kb.
• 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 SCD 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 SCD 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 erythroid enhancer within intron 2 (e.g., between TSS+0.75 kb to TSS+52.0 kb), and the second set of breaks (either the double strand break or the pair of single strand breaks) is positioned downstream of the erythroid enhancer within intron 2 (e.g., between TSS+64.4 kb to TSS+84.7 kb) (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+0.75 kb to TSS+52.0 kb), 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+52.0 kb to TSS+64.4 kb),
    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:
  • (1) downstream the 3′ end of the erythroid enhancer in intron 2 (e.g., between TSS+64.4 kb to TSS+84.7 kb), 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+52.0 kb to TSS+64.4 kb).
• 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+0.75 kb to TSS+10 kb,
• (2) between TSS+10 kb to TSS+20 kb,
• (3) between TSS+20 kb to TSS+30 kb,
• (4) between TSS+30 kb to TSS+40 kb,
• (5) between TSS+40 kb to TSS+45 kb,
• (6) between TSS+45 kb to TSS+47.5 kb,
• (7) between TSS+47.5 kb to TSS+50 kb,
• (8) between TSS+50 kb to TSS+51 kb,
• (9) between TSS+51 kb to TSS+51.1 kb,
• (10) between TSS+51.1 kb to TSS+51.2 kb,
• (11) between TSS+51.2 kb to TSS+51.3 kb,
• (12) between TSS+51.3 kb to TSS+51.4 kb,
• (13) between TSS+51.4 kb to TSS+51.5 kb,
• (14) between TSS+51.5 kb to TSS+51.6 kb,
• (15) between TSS+51.6 kb to TSS+51.7 kb,
• (16) between TSS+51.7 kb to TSS+51.8 kb,
• (17) between TSS+51.8 kb to TSS+51.9 kb,
• (18) between TSS+51.9 kb to TSS+52 kb,
• (19) between TSS+52 kb to TSS+53 kb,
• (20) between TSS+53 kb to TSS+54 kb,
• (21) between TSS+54 kb to TSS+55 kb,
• (22) between TSS+55 kb to TSS+56 kb,
• (23) between TSS+56 kb to TSS+57 kb,
• (24) between TSS+57 kb to TSS+58 kb,
• (25) between TSS+58 kb to TSS+59 kb,
• (26) between TSS+59 kb to TSS+60 kb,
• (27) between TSS+60 kb to TSS+61 kb,
• (28) between TSS+61 kb to TSS+62 kb,
• (29) between TSS+62 kb to TSS+63 kb,
• (30) between TSS+63 kb to TSS+64 kb, or
• (31) between TSS+64 kb to TSS+64.4 kb,
• 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 BCL11A gene:
• (1) between TSS+52 kb to TSS+53 kb,
• (2) between TSS+53 kb to TSS+54 kb,
• (3) between TSS+54 kb to TSS+55 kb,
• (4) between TSS+55 kb to TSS+56 kb,
• (5) between TSS+56 kb to TSS+57 kb,
• (6) between TSS+57 kb to TSS+58 kb,
• (7) between TSS+58 kb to TSS+59 kb,
• (8) between TSS+59 kb to TSS+60 kb,
• (9) between TSS+60 kb to TSS+61 kb,
• (10) between TSS+61 kb to TSS+62 kb,
• (11) between TSS+62 kb to TSS+63 kb,
• (12) between TSS+63 kb to TSS+64 kb,
• (13) between TSS+64 kb to TSS+64.4 kb,
• (14) between TSS+64.4 kb to TSS+65 kb,
• (15) between TSS+65 kb to TSS+65.1 kb,
• (16) between TSS+65.1 kb to TSS+65.2 kb,
• (17) between TSS+65.2 kb to TSS+65.3 kb,
• (18) between TSS+65.3 kb to TSS+65.4 kb,
• (19) between TSS+65.4 kb to TSS+65.5 kb,
• (20) between TSS+65.5 kb to TSS+65.7 kb,
• (21) between TSS+65.7 kb to TSS+65.8 kb,
• (22) between TSS+65.8 kb to TSS+65.9 kb,
• (23) between TSS+65.9 kb to TSS+66 kb,
• (24) between TSS+66 kb to TSS+67 kb,
• (25) between TSS+67 kb to TSS+68 kb,
• (26) between TSS+68 kb to TSS+69 kb,
• (27) between TSS+69 kb to TSS+70 kb,
• (28) between TSS+70 kb to TSS+75 kb,
• (29) between TSS+75 kb to TSS+80 kb, or
• (30) between TSS+80 kb to TSS+84.4 kb.
• 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 SCD 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 SCD target knockdown position (e.g., the erythroid enhancer) in the BCL11A gene. In an embodiment, the first set of breaks (i.e., the first pair of single strand breaks) is positioned upstream of the erythroid enhancer within intron 2 (e.g., between TSS+0.75 kb to TSS+52.0 kb), and the second set of breaks (i.e., the second pair of single strand breaks) is positioned downstream of the erythroid enhancer within intron 2 (e.g., between TSS+64.4 kb to TSS+84.7 kb) (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:
• • (1) upstream of the 5′ end of the erythroid enhancer in intron 2 (e.g., between TSS+0.75 kb to TSS+52.0 kb), 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+52.0 kb to TSS+64.4 kb),
    and the second pair of single strand breaks to be paired with the first pair of single strand breaks may be positioned as follows:
  • (1) downstream the 3′ end of the erythroid enhancer in intron 2 (e.g., between TSS+64.4 kb to TSS+84.7 kb), 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+52.0 kb to TSS+64.4 kb).
• For example, the pair of single strand breaks may be positioned in the BCL11A gene:
• (1) between TSS+0.75 kb to TSS+10 kb,
• (2) between TSS+10 kb to TSS+20 kb,
• (3) between TSS+20 kb to TSS+30 kb,
• (4) between TSS+30 kb to TSS+40 kb,
• (5) between TSS+40 kb to TSS+45 kb,
• (6) between TSS+45 kb to TSS+47.5 kb,
• (7) between TSS+47.5 kb to TSS+50 kb,
• (8) between TSS+50 kb to TSS+51 kb,
• (9) between TSS+51 kb to TSS+51.1 kb,
• (10) between TSS+51.1 kb to TSS+51.2 kb,
• (11) between TSS+51.2 kb to TSS+51.3 kb,
• (12) between TSS+51.3 kb to TSS+51.4 kb,
• (13) between TSS+51.4 kb to TSS+51.5 kb,
• (14) between TSS+51.5 kb to TSS+51.6 kb,
• (15) between TSS+51.6 kb to TSS+51.7 kb,
• (16) between TSS+51.7 kb to TSS+51.8 kb,
• (17) between TSS+51.8 kb to TSS+51.9 kb,
• (18) between TSS+51.9 kb to TSS+52 kb,
• (19) between TSS+52 kb to TSS+53 kb,
• (20) between TSS+53 kb to TSS+54 kb,
• (21) between TSS+54 kb to TSS+55 kb,
• (22) between TSS+55 kb to TSS+56 kb,
• (23) between TSS+56 kb to TSS+57 kb,
• (24) between TSS+57 kb to TSS+58 kb,
• (25) between TSS+58 kb to TSS+59 kb,
• (26) between TSS+59 kb to TSS+60 kb,
• (27) between TSS+60 kb to TSS+61 kb,
• (28) between TSS+61 kb to TSS+62 kb,
• (29) between TSS+62 kb to TSS+63 kb,
• (30) between TSS+63 kb to TSS+64 kb, or
• (31) between TSS+64 kb to TSS+64.4 kb,
• 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+52 kb to TSS+53 kb,
• (2) between TSS+53 kb to TSS+54 kb,
• (3) between TSS+54 kb to TSS+55 kb,
• (4) between TSS+55 kb to TSS+56 kb,
• (5) between TSS+56 kb to TSS+57 kb,
• (6) between TSS+57 kb to TSS+58 kb,
• (7) between TSS+58 kb to TSS+59 kb,
• (8) between TSS+59 kb to TSS+60 kb,
• (9) between TSS+60 kb to TSS+61 kb,
• (10) between TSS+61 kb to TSS+62 kb,
• (11) between TSS+62 kb to TSS+63 kb,
• (12) between TSS+63 kb to TSS+64 kb,
• (13) between TSS+64 kb to TSS+64.4 kb,
• (14) between TSS+64.4 kb to TSS+65 kb,
• (15) between TSS+65 kb to TSS+65.1 kb,
• (16) between TSS+65.1 kb to TSS+65.2 kb,
• (17) between TSS+65.2 kb to TSS+65.3 kb,
• (18) between TSS+65.3 kb to TSS+65.4 kb,
• (19) between TSS+65.4 kb to TSS+65.5 kb,
• (20) between TSS+65.5 kb to TSS+65.7 kb,
• (21) between TSS+65.7 kb to TSS+65.8 kb,
• (22) between TSS+65.8 kb to TSS+65.9 kb,
• (23) between TSS+65.9 kb to TSS+66 kb,
• (24) between TSS+66 kb to TSS+67 kb,
• (25) between TSS+67 kb to TSS+68 kb,
• (26) between TSS+68 kb to TSS+69 kb,
• (27) between TSS+69 kb to TSS+70 kb,
• (28) between TSS+70 kb to TSS+75 kb,
• (29) between TSS+75 kb to TSS+80 kb, or
• (30) between TSS+80 kb to TSS+84.4 kb.
• 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 BCL11A gene.
• Knocking Down the BCL11A 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 BCL11A gene product. As described herein, 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 BCL11A gene. In an embodiment, one or more eiCas9s may be used to block binding of one or more endogenous transcription factors. In another embodiment, an eiCas9 can be fused to a chromatin modifying protein. Altering chromatin status can result in decreased expression of the target gene. One or more eiCas9s fused to one or more chromatin modifying proteins may be used to alter chromatin status.
• Methods and compositions discussed herein may be used to alter the expression of the BCL11A gene to treat or prevent SCD by targeting a promoter region of the BCL11A 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 BCL11A gene. In an embodiment, the methods and compositions discussed herein may be used to knock down the BCL11A gene to treat or prevent SCD by targeting 0.5 kb upstream or downstream of the TSS. A targeted knockdown approach reduces or eliminates expression of functional BCL11A gene product. As described herein, 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 BCL11A gene.
• Methods to Treat or Prevent Sickle Cell Disease (SCD)
• Disclosed herein are the approaches to treat or prevent SCD, using the compositions and methods described herein.
• One approach to treat or prevent SCD is to repair (i.e., correct) one or more mutations in the HBB gene, e.g., by HDR. In this approach, mutant HBB allele(s) are corrected and restored to wild type state. While not wishing to be bound by theory, it is believed that correction of the glutamic acid to valine substitution at amino acid 6 in the beta-globin gene restores wild type beta-globin production within erythroid cells. The method described herein can be performed in all cell types. Beta-globin is expressed in cells of erythroid cell lineage. In an embodiment, an erythroid cell is targeted.
• In an embodiment, one HBB allele is repaired in the subject. In another embodiment, both HBB alleles are repaired in the subject. In either situation, the subjects can be cured of disease. As the disease only displays a phenotype when both alleles are mutated, repair of a single allele is adequate for a cure.
• In one approach, the BCL11A 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 SCD 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 BCL11A gene increases fetal hemoglobin levels in beta-thalassemia subjects and improves phenotype and/or reduces or prevents disease progression. BCL11A 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 BCL11A 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 BCL11A knockout or knockdown is targeted specifically to cells of the erythroid lineage. BCL11A 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 SCD. 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 BCL11A 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 SCD. 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 pre-conditioning 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 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 FIGS. 1A-1G. While not wishing to be bound by theory, in an embodiment, with regard to the three dimensional form, or intra- or inter-strand interactions of an active form of a gRNA, regions of high complementarity are sometimes shown as duplexes in FIGS. 1A-1G and other depictions provided herein.
• In an embodiment, a unimolecular, or chimeric, gRNA comprises, preferably from 5′ to 3′:
• • a targeting domain (which is complementary to a target nucleic acid in the HBB gene or BCL11A gene, e.g., a targeting domain from any of Tables 1A-1D, 2A-2F, 3A-3C, 4A-4E, 5A-5E, 6A-6B, 7A-7D, 8A-8D, 9, 10A-10D, 11A-11D, 12, 13A-13D, 14A-14C, 15A-15D, 16A-16E, 17A-17B, 18A-18C, 19A-19E, 20A-20C, 21A-21E, 22A-22E, 23A-23C, 24A-24D, 25A-25B, 26, 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 HBB gene or BCL11A gene, e.g., a targeting domain from Tables 1A-1D, 2A-2F, 3A-3C, 4A-4E, 5A-5E, 6A-6B, 7A-7D, 8A-8D, 9, 10A-10D, 11A-11D, 12, 13A-13D, 14A-14C, 15A-15D, 16A-16E, 17A-17B, 18A-18C, 19A-19E, 20A-20C, 21A-21E, 22A-22E, 23A-23C, 24A-24D, 25A-25B, 26, 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 to 9, e.g., 4, 5, 6, 7, 8 or 9 nucleotides in length. In an embodiment, the central subdomain is 1, 2, or 3, e.g., 1, nucleotide in length. In an embodiment, the 3′ subdomain is 3 to 25, e.g., 4 to 22, 4 to 18, or 4 to 10, or 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25 nucleotides in length.
• The first complementarity domain can share homology with, or be derived from, a naturally occurring first complementarity domain. In an embodiment, it has at least 50% 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. 1B-1E. 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 provides 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 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. 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.
• Some or all of the nucleotides of the domain can have a modification, e.g., a modification found in Section VIII herein.
• A Proximal domain
• FIGS. 1A-1G provide examples of proximal domains.
• In an embodiment, the proximal domain is 5 to 20 nucleotides in length. In an embodiment, the proximal domain can share homology with or be derived from a naturally occurring proximal domain. In an embodiment, it has at least 50% homology with a proximal domain disclosed herein, e.g., an S. pyogenes, S. aureus or S. thermophilus, proximal domain.
• Some or all of the nucleotides of the domain can have a modification, e.g., 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., panels 4a or 5a of FIG. 1D or FIG. 1E. 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 S H et al., Nature 2014 (doi: 10.1038/nature13011).
• 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 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+/−2, 7+/−2, 8+/−2, 9+/−2, 10+/−2, 11+/−2, 12+/−2, 13+/−2, 14+/−2, 15+/−2, or 16+−2, nucleotides in length.
• In an embodiment, the core domain and targeting domain, are independently, 10+/−2 nucleotides in length.
• In an embodiment, the core domain and targeting domain, are independently, 10+/−4 nucleotides in length.
• In an embodiment, the core domain and targeting domain are independently 6, 7, 8, 9, 10, 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 modification at the 2′ position on ribose), 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 modification at the 2′ position on ribose), e.g., a 2-acetylation, e.g., a 2′ methylation, or other modification 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 degree of complementarity, together with other properties of the gRNA, is sufficient to allow targeting of a Cas9 molecule to the target nucleic acid.
• In an embodiment, the first and second complementarity domains are:
• independently, 6+/−2, 7+/−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 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 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):

• (SEQ ID NO: 5)

  NNNNNNNNNNNNNNNNNNNNGUUUUAGAGCUAGAAAUAGCAAGUUAAAA

  UAAGGCUAGUCCGUUAUCAACUUGAAAAAGUGGCACCGAGUCGGUGC.

• 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):

• (SEQ ID NO: 27)

  NNNNNNNNNNNNNNNNNNNNGUUUUAGAGCUAUGCUGAAAAGCAUAGCA

  AGUUAAAAUAAGGCUAGUCCGUUAUCAACUUGAAAAAGUGGCACCGAGU

  CGGUGC.

• 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):

• (SEQ ID NO: 28)

  NNNNNNNNNNNNNNNNNNNNGUUUUAGAGCUAUGCUGGAAACAGCAUAG

  CAAGUUAAAAUAAGGCUAGUCCGUUAUCAACUUGAAAAAGUGGCACCGA

  GUCGGUGC.

• 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):

• (SEQ ID NO: 29)

  NNNNNNNNNNNNNNNNNNNNGUUUUAGAGCUAUGCUGUUUUGGAAACAA

  AACAGCAUAGCAAGUUAAAAUAAGGCUAGUCCGUUAUCAACUUGAAAAA

  GUGGCACCGAGUCGGUGC.

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

• (SEQ ID NO: 30)

  NNNNNNNNNNNNNNNNNNNNGUAUUAGAGCUAGAAAUAGCAAGUUAAUA

  UAAGGCUAGUCCGUUAUCAACUUGAAAAAGUGGCACCGAGUCGGUGC;

  (SEQ ID NO: 31)

  NNNNNNNNNNNNNNNNNNNNGUUUAAGAGCUAGAAAUAGCAAGUUUAAA

  UAAGGCUAGUCCGUUAUCAACUUGAAAAAGUGGCACCGAGUCGGUGC;

  or

  (SEQ ID NO: 32)

  NNNNNNNNNNNNNNNNNNNNGUAUUAGAGCUAUGCUGUAUUGGAAACAA

  UACAGCAUAGCAAGUUAAUAUAAGGCUAGUCCGUUAUCAACUUGAAAAA

  GUGGCACCGAGUCGGUGC.

• 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 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 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 so as to not interfere with gRNA molecule efficacy, which can be evaluated by testing a candidate modification in the system described in Section IV. gRNAs having a candidate 5′ extension domain having a selected length, sequence, degree of complementarity, or degree of modification, can be evaluated in the system described at Section IV. The candidate 5′ extension domain can be placed, either alone, or with one or more other candidate changes in a gRNA molecule/Cas9 molecule system known to be functional with a selected target and evaluated.
• In an embodiment, the 5′ extension domain has at least 60, 70, 80, 85, 90 or 95% homology with, or differs by no more than 1, 2, 3, 4, 5, or 6 nucleotides from, a reference 5′ extension domain, e.g., a naturally occurring, e.g., an S. pyogenes, 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 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 linking domain can comprise as many as 1, 2, 3, 4, 5, 6, 7 or 8 modifications.
• Modifications in a linking domain can be selected so as to not interfere with targeting efficacy, which can be evaluated by testing a candidate modification in the system described in Section IV. gRNAs having a candidate linking domain having a selected length, sequence, degree of complementarity, or degree of modification, can be evaluated a system described in 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 30 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+/−2, 7+/−2, 8+/−2, 9+/−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 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 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 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 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:

• (SEQ ID NO: 33)

  AAGGCUAGUCCGUUAUCAACUUGAAAAAGUGGCACCGAGUCGGUGCU,

  or

  (SEQ ID NO: 34)

  AAGGCUAGUCCGUUAUCAACUUGAAAAAGUGGCACCGAGUCGGUGGUG

  C,

  or

  (SEQ ID NO: 35)

  AAGGCUAGUCCGUUAUCAACUUGAAAAAGUGGCACCGAGUCGGUGCGGA

  UC,

  or

  (SEQ ID NO: 36)

  AAGGCUAGUCCGUUAUCAACUUGAAAAAGUG,

  or

  (SEQ ID NO: 37)

  AAGGCUAGUCCGUUAUCA,

  or

  (SEQ ID NO: 38)

  AAGGCUAGUCCG.

• 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 H1 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 3′:
• • 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, 45, 49, 50, or 53 nucleotides 3′ to the last nucleotide of the second complementarity domain.
• In an embodiment, the targeting domain comprises, has, or consists of, 20 nucleotides (e.g., 20 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 20 nucleotides in length; and there are at least 16, 19, 21, 26, 31, 32, 36, 41, 46, 50, 51, or 54 nucleotides 3′ to the last nucleotide of the second complementarity domain that is complementary to its corresponding nucleotide of the first complementarity domain.
• In an embodiment, the targeting domain comprises, has, or consists of, 21 nucleotides (e.g., 21 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 21 nucleotides in length; and the proximal and tail domain, when taken together, comprise at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides.
• In an embodiment, the targeting domain comprises, has, or consists of, 21 nucleotides (e.g., 21 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 21 nucleotides in length; and there are at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides 3′ to the last nucleotide of the second complementarity domain.
• In an embodiment, the targeting domain comprises, has, or consists of, 21 nucleotides (e.g., 21 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 21 nucleotides in length; and there are at least 16, 19, 21, 26, 31, 32, 36, 41, 46, 50, 51, or 54 nucleotides 3′ to the last nucleotide of the second complementarity domain that is complementary to its corresponding nucleotide of the first complementarity domain.
• In an embodiment, the targeting domain comprises, has, or consists of, 22 nucleotides (e.g., 22 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 22 nucleotides in length; and the proximal and tail domain, when taken together, comprise at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides.
• In an embodiment, the targeting domain comprises, has, or consists of, 22 nucleotides (e.g., 22 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 22 nucleotides in length; and there are at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides 3′ to the last nucleotide of the second complementarity domain.
• In an embodiment, the targeting domain comprises, has, or consists of, 22 nucleotides (e.g., 22 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 22 nucleotides in length; and there are at least 16, 19, 21, 26, 31, 32, 36, 41, 46, 50, 51, or 54 nucleotides 3′ to the last nucleotide of the second complementarity domain that is complementary to its corresponding nucleotide of the first complementarity domain.
• In an embodiment, the targeting domain comprises, has, or consists of, 23 nucleotides (e.g., 23 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 23 nucleotides in length; and the proximal and tail domain, when taken together, comprise at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides.
• In an embodiment, the targeting domain comprises, has, or consists of, 23 nucleotides (e.g., 23 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 23 nucleotides in length; and there are at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides 3′ to the last nucleotide of the second complementarity domain.
• In an embodiment, the targeting domain comprises, has, or consists of, 23 nucleotides (e.g., 23 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 23 nucleotides in length; and there are at least 16, 19, 21, 26, 31, 32, 36, 41, 46, 50, 51, or 54 nucleotides 3′ to the last nucleotide of the second complementarity domain that is complementary to its corresponding nucleotide of the first complementarity domain.
• In an embodiment, the targeting domain comprises, has, or consists of, 24 nucleotides (e.g., 24 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 24 nucleotides in length; and the proximal and tail domain, when taken together, comprise at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides.
• In an embodiment, the targeting domain comprises, has, or consists of, 24 nucleotides (e.g., 24 consecutive nucleotides) having complementarity with the target domain, e.g., the 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-11 .
• Exemplary Modular gRNAs
• In an embodiment, a modular gRNA comprises:
• • a first strand comprising, preferably from 5′ to 3′;
    • a targeting domain, e.g., comprising 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, or 26 nucleotides;
    • a first complementarity domain; and
    • a second strand, comprising, preferably from 5′ to 3′:
    • optionally a 5′ extension domain;
    • a second complementarity domain;
    • a proximal domain; and
    • a tail domain,
  • wherein:
  • (a) the proximal and tail domain, when taken together, comprise at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides;
  • (b) there are at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides 3′ to the last nucleotide of the second complementarity domain; or
  • (c) there are at least 16, 19, 21, 26, 31, 32, 36, 41, 46, 50, 51, or 54 nucleotides 3′ to the last nucleotide of the second complementarity domain that is complementary to its corresponding nucleotide of the first complementarity domain.
• In an embodiment, the sequence from (a), (b), or (c), has at least 60, 75, 80, 85, 90, 95, or 99% homology with the corresponding sequence of a naturally occurring gRNA, or with a gRNA described herein.
• In an embodiment, the proximal and tail domain, when taken together, comprise at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides.
• 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 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 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 5 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 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 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 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 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 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 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, 45, 49, 50, or 53 nucleotides 3′ to the last nucleotide of the second complementarity domain.
• In an embodiment, the targeting domain comprises, has, or consists of, 20 nucleotides (e.g., 20 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 20 nucleotides in length; and there are at least 16, 19, 21, 26, 31, 32, 36, 41, 46, 50, 51, or 54 nucleotides 3′ to the last nucleotide of the second complementarity domain that is complementary to its corresponding nucleotide of the first complementarity domain.
• In an embodiment, the targeting domain comprises, has, or consists of, 21 nucleotides (e.g., 21 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 21 nucleotides in length; and the proximal and tail domain, when taken together, comprise at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides.
• In an embodiment, the targeting domain comprises, has, or consists of, 21 nucleotides (e.g., 21 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 21 nucleotides in length; and there are at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides 3′ to the last nucleotide of the second complementarity domain.
• In an embodiment, the targeting domain comprises, has, or consists of, 21 nucleotides (e.g., 21 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 21 nucleotides in length; and there are at least 16, 19, 21, 26, 31, 32, 36, 41, 46, 50, 51, or 54 nucleotides 3′ to the last nucleotide of the second complementarity domain that is complementary to its corresponding nucleotide of the first complementarity domain.
• In an embodiment, the targeting domain comprises, has, or consists of, 22 nucleotides (e.g., 22 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 22 nucleotides in length; and the proximal and tail domain, when taken together, comprise at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides.
• In an embodiment, the targeting domain comprises, has, or consists of, 22 nucleotides (e.g., 22 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 22 nucleotides in length; and there are at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides 3′ to the last nucleotide of the second complementarity domain.
• In an embodiment, the targeting domain comprises, has, or consists of, 22 nucleotides (e.g., 22 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 22 nucleotides in length; and there are at least 16, 19, 21, 26, 31, 32, 36, 41, 46, 50, 51, or 54 nucleotides 3′ to the last nucleotide of the second complementarity domain that is complementary to its corresponding nucleotide of the first complementarity domain.
• In an embodiment, the targeting domain comprises, has, or consists of, 23 nucleotides (e.g., 23 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 23 nucleotides in length; and the proximal and tail domain, when taken together, comprise at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides.
• In an embodiment, the targeting domain comprises, has, or consists of, 23 nucleotides (e.g., 23 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 23 nucleotides in length; and there are at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides 3′ to the last nucleotide of the second complementarity domain.
• In an embodiment, the targeting domain comprises, has, or consists of, 23 nucleotides (e.g., 23 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 23 nucleotides in length; and there are at least 16, 19, 21, 26, 31, 32, 36, 41, 46, 50, 51, or 54 nucleotides 3′ to the last nucleotide of the second complementarity domain that is complementary to its corresponding nucleotide of the first complementarity domain.
• In an embodiment, the targeting domain comprises, has, or consists of, 24 nucleotides (e.g., 24 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 24 nucleotides in length; and the proximal and tail domain, when taken together, comprise at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides.
• In an embodiment, the targeting domain comprises, has, or consists of, 24 nucleotides (e.g., 24 consecutive nucleotides) having complementarity with the target domain, e.g., the 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.
• 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 11(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 J S. 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. Targeting domains, disclosed herein, may comprise the 17-mer described in Tables 1A-1D, 2A-2F, 3A-3C, 4A-4E, 5A-5E, 6A-6B, 7A-7D, 8A-8D, 9, 10A-10D, 11A-11D, 12, 13A-13D, 14A-14C, 15A-15D, 16A-16E, 17A-17B, 18A-18C, 19A-19E, 20A-20C, 21A-21E, 22A-22E, 23A-23C, 24A-24D, 25A-25B, 26, or 31, e.g., the targeting domains of 18 or more nucleotides may comprise the 17-mer gRNAs described in Tables 1A-1D, 2A-2F, 3A-3C, 4A-4E, 5A-5E, 6A-6B, 7A-7D, 8A-8D, 9, 10A-10D, 11A-11D, 12, 13A-13D, 14A-14C, 15A-15D, 16A-16E, 17A-17B, 18A-18C, 19A-19E, 20A-20C, 21A-21E, 22A-22E, 23A-23C, 24A-24D, 25A-25B, 26, or 31. Targeting domains, disclosed herein, may comprises the 18-mer described in Tables 1A-1D, 2A-2F, 3A-3C, 4A-4E, 5A-5E, 6A-6B, 7A-7D, 8A-8D, 9, 10A-10D, 11A-11D, 12, 13A-13D, 14A-14C, 15A-15D, 16A-16E, 17A-17B, 18A-18C, 19A-19E, 20A-20C, 21A-21E, 22A-22E, 23A-23C, 24A-24D, 25A-25B, 26, or 31, e.g., the targeting domains of 19 or more nucleotides may comprise the 18-mer gRNAs described in Tables 1A-1D, 2A-2F, 3A-3C, 4A-4E, 5A-5E, 6A-6B, 7A-7D, 8A-8D, 9, 10A-10D, 11A-11D, 12, 13A-13D, 14A-14C, 15A-15D, 16A-16E, 17A-17B, 18A-18C, 19A-19E, 20A-20C, 21A-21E, 22A-22E, 23A-23C, 24A-24D, 25A-25B, 26, or 31. Targeting domains, disclosed herein, may comprises the 19-mer described in Tables 1A-1D, 2A-2F, 3A-3C, 4A-4E, 5A-5E, 6A-6B, 7A-7D, 8A-8D, 9, 10A-10D, 11A-11D, 12, 13A-13D, 14A-14C, 15A-15D, 16A-16E, 17A-17B, 18A-18C, 19A-19E, 20A-20C, 21A-21E, 22A-22E, 23A-23C, 24A-24D, 25A-25B, 26, or 31, e.g., the targeting domains of 20 or more nucleotides may comprise the 19-mer gRNAs described in Tables 1A-1D, 2A-2F, 3A-3C, 4A-4E, 5A-5E, 6A-6B, 7A-7D, 8A-8D, 9, 10A-10D, 11A-11D, 12, 13A-13D, 14A-14C, 15A-15D, 16A-16E, 17A-17B, 18A-18C, 19A-19E, 20A-20C, 21A-21E, 22A-22E, 23A-23C, 24A-24D, 25A-25B, 26, or 31. Targeting domains, disclosed herein, may comprises the 20-mer gRNAs described in Tables 1A-1D, 2A-2F, 3A-3C, 4A-4E, 5A-5E, 6A-6B, 7A-7D, 8A-8D, 9, 10A-10D, 11A-11D, 12, 13A-13D, 14A-14C, 15A-15D, 16A-16E, 17A-17B, 18A-18C, 19A-19E, 20A-20C, 21A-21E, 22A-22E, 23A-23C, 24A-24D, 25A-25B, 26, or 31, e.g., the targeting domains of 21 or more nucleotides may comprise the 20-mer gRNAs described in Tables 1A-1D, 2A-2F, 3A-3C, 4A-4E, 5A-5E, 6A-6B, 7A-7D, 8A-8D, 9, 10A-10D, 11A-11D, 12, 13A-13D, 14A-14C, 15A-15D, 16A-16E, 17A-17B, 18A-18C, 19A-19E, 20A-20C, 21A-21E, 22A-22E, 23A-23C, 24A-24D, 25A-25B, 26, or 31. Targeting domains, disclosed herein, may comprises the 21-mer described in Tables 1A-1D, 2A-2F, 3A-3C, 4A-4E, 5A-5E, 6A-6B, 7A-7D, 8A-8D, 9, 10A-10D, 11A-11D, 12, 13A-13D, 14A-14C, 15A-15D, 16A-16E, 17A-17B, 18A-18C, 19A-19E, 20A-20C, 21A-21E, 22A-22E, 23A-23C, 24A-24D, 25A-25B, 26, or 31, e.g., the targeting domains of 22 or more nucleotides may comprise the 21-mer gRNAs described in Tables 1A-1D, 2A-2F, 3A-3C, 4A-4E, 5A-5E, 6A-6B, 7A-7D, 8A-8D, 9, 10A-10D, 11A-11D, 12, 13A-13D, 14A-14C, 15A-15D, 16A-16E, 17A-17B, 18A-18C, 19A-19E, 20A-20C, 21A-21E, 22A-22E, 23A-23C, 24A-24D, 25A-25B, 26, or 31. Targeting domains, disclosed herein, may comprises the 22-mer described in Tables 1A-1D, 2A-2F, 3A-3C, 4A-4E, 5A-5E, 6A-6B, 7A-7D, 8A-8D, 9, 10A-10D, 11A-11D, 12, 13A-13D, 14A-14C, 15A-15D, 16A-16E, 17A-17B, 18A-18C, 19A-19E, 20A-20C, 21A-21E, 22A-22E, 23A-23C, 24A-24D, 25A-25B, 26, or 31, e.g., the targeting domains of 23 or more nucleotides may comprise the 22-mer gRNAs described in Tables 1A-1D, 2A-2F, 3A-3C, 4A-4E, 5A-5E, 6A-6B, 7A-7D, 8A-8D, 9, 10A-10D, 11A-11D, 12, 13A-13D, 14A-14C, 15A-15D, 16A-16E, 17A-17B, 18A-18C, 19A-19E, 20A-20C, 21A-21E, 22A-22E, 23A-23C, 24A-24D, 25A-25B, 26, or 31. Targeting domains, disclosed herein, may comprises the 23-mer described in Tables 1A-1D, 2A-2F, 3A-3C, 4A-4E, 5A-5E, 6A-6B, 7A-7D, 8A-8D, 9, 10A-10D, 11A-11D, 12, 13A-13D, 14A-14C, 15A-15D, 16A-16E, 17A-17B, 18A-18C, 19A-19E, 20A-20C, 21A-21E, 22A-22E, 23A-23C, 24A-24D, 25A-25B, 26, or 31, e.g., the targeting domains of 24 or more nucleotides may comprise the 23-mer gRNAs described in Tables 1A-1D, 2A-2F, 3A-3C, 4A-4E, 5A-5E, 6A-6B, 7A-7D, 8A-8D, 9, 10A-10D, 11A-11D, 12, 13A-13D, 14A-14C, 15A-15D, 16A-16E, 17A-17B, 18A-18C, 19A-19E, 20A-20C, 21A-21E, 22A-22E, 23A-23C, 24A-24D, 25A-25B, 26, or 31. Targeting domains, disclosed herein, may comprises the 24-mer described in Tables 1A-1D, 2A-2F, 3A-3C, 4A-4E, 5A-5E, 6A-6B, 7A-7D, 8A-8D, 9, 10A-10D, 11A-11D, 12, 13A-13D, 14A-14C, 15A-15D, 16A-16E, 17A-17B, 18A-18C, 19A-19E, 20A-20C, 21A-21E, 22A-22E, 23A-23C, 24A-24D, 25A-25B, 26, or 31, e.g., the targeting domains of 25 or more nucleotides may comprise the 24-mer gRNAs described in Tables 1A-1D, 2A-2F, 3A-3C, 4A-4E, 5A-5E, 6A-6B, 7A-7D, 8A-8D, 9, 15 10A-10D, 11A-11D, 12, 13A-13D, 14A-14C, 15A-15D, 16A-16E, 17A-17B, 18A-18C, 19A-19E, 20A-20C, 21A-21E, 22A-22E, 23A-23C, 24A-24D, 25A-25B, 26, 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 Correct a Mutation in the HBB Gene
• gRNAs were designed for use with S. pyogenes, and S. aureus Cas9 enzymes to target the E6V mutation in the HBB gene. As an example, three strategies were utilized to identify gRNAs for use with S. pyogenes, S. aureus and N. meningitidis Cas9 enzymes.
• In one strategy, the gRNAs were identified and ranked into 3 tiers for S. pyogenes (Tables 1A-1C). The targeting domains for tier 1 gRNA molecules for use with the S. pyogenes Cas9 to target the E6V mutation in the HBB 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. Note that tiers are non-inclusive (each gRNA is listed only once). gRNAs for use with the S. aureus (Table 1D), 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.
• In a second strategy, the gRNAs were identified and ranked into 4 tiers for S. pyogenes (Tables 13A-13D) and 5 tiers for S. aureus (Tables 14A-14C). The targeting domain for tier 1 gRNA molecules to use with S. pyogenes Cas9 were selected based on (1) a short distance to the target position, e.g., within 100 bp upstream and 100 bp downstream of the mutation, (2) a high level of orthogonality, and (3) the presence of a 5′ G. For selection of tier 2 gRNAs, a short 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. The targeting domain for tier 1 gRNA molecules to use with S. aureus Cas9 were selected based on (1) a short distance to the target position, e.g., within 100 bp upstream and 100 bp downstream of the mutation, (2) a high level of orthogonality, and (3) the presence of a 5′ G. For selection of tier 2 gRNAs, a short 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. Tier 5 is selected based on (1) a short distance to the target position, e.g., within 100 bp upstream and 100 bp downstream of the mutation and (2) PAM is NNGRRV. Note that tiers are non-inclusive (each gRNA is listed only once for the strategy). In certain instances, no gRNA was identified based on the criteria of the particular tier. In some instances, there are no corresponding exemplary gRNAs in certain tiers.
• In a third strategy, the gRNAs were identified and ranked into 3 tiers for S. pyogenes (Tables 24A-24D), 4 tiers for S. aureus (Tables 25A-25B) and 3 tiers for N. meningitidis (Tables 26). The targeting domain for tier 1 gRNA molecules to use with S. pyogenes Cas9 were selected based on (1) distance to the target position, e.g., within 200 bp upstream and 200 bp downstream of the mutation and (2) a high level of orthogonality. The targeting domain for tier 2 gRNA molecules to use with S. pyogenes Cas9 were selected based on (1) distance to the target position, e.g., within 200 bp upstream and 200 bp downstream of the mutation and (2) the presence of a 5′G. The targeting domain for tier 3 gRNA molecules to use with S. pyogenes Cas9 were selected based on distance to the target position, e.g., within 200 bp upstream and 200 bp downstream of the mutation. The targeting domain for tier 1 gRNA molecules to use with S. aureus Cas9 were selected based on (1) distance to the target position, e.g., within 200 bp upstream and 200 bp downstream of the mutation, (2) a high level of orthogonality and (3) PAM is NNGRRT. The targeting domain for tier 2 gRNA molecules to use with S. aureus Cas9 were selected based on (1) distance to the target position, e.g., within 200 bp upstream and 200 bp downstream of the mutation, (2) the presence of a 5′G, and (3) PAM is NNGRRT. The targeting domain for tier 3 gRNA molecules to use with S. aureus Cas9 were selected based on (1) distance to the target position, e.g., within 200 bp upstream and 200 bp downstream of the mutation and (2) PAM is NNGRRT. The targeting domain for tier 4 gRNA molecules to use with S. aureus Cas9 were selected based on (1) distance to the target position, e.g., within 200 bp upstream and 200 bp downstream of the mutation and (2) PAM is NNGRRV. The targeting domain for tier 1 gRNA molecules to use with N. meningitidis Cas9 were selected based on (1) distance to the target position, e.g., within 200 bp upstream and 200 bp downstream of the mutation and (2) a high level of orthogonality. The targeting domain for tier 2 gRNA molecules to use with N. meningitidis Cas9 were selected based on (1) distance to the target position, e.g., within 200 bp upstream and 200 bp downstream of the mutation and (2) the presence of a 5′G. The targeting domain for tier 3 gRNA molecules to use with N. meningitidis Cas9 were selected based on distance to the target position, e.g., within 200 bp upstream and 200 bp downstream of the mutation.
• 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 0-50 bp. Exemplary nickase pairs including selecting a targeting domain from Group A and a second targeting domain from Group B in Table 24D (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 Table 24D (for S. pyogenes). For example, HBB-9, HBB-20can be combined with HBB-11, HBB-39.
• Strategies to Identify gRNAs for S. pyogenes, S. aureus, and N. meningitidis to Knock Out the BCL11A 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 one strategy, the gRNAs were identified and ranked into 4 tires for S. pyogenes (Tables 2A-2D). 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 2E), and N. meningitidis (Table 2F) 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 4A-4E), and S. aureus (Tables 5A-5E); and 2 tiers for N. meningitidis (Tables 6A-6B). 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., start codon), e.g., within 500 bp (e.g., downstream) of the target site (e.g., start codon), (2) a high level of orthogonality and (3) the presence of 5′G. The targeting domain for tier 2 gRNA molecules were selected based on (1) distance to a target site (e.g., start codon), e.g., within 500 bp (e.g., downstream) of the target site (e.g., start codon) and (2) a high level of orthogonality. The targeting domain for tier 3 gRNA molecules were selected based on (1) distance to a target site (e.g., start codon), e.g., within 500 bp (e.g., downstream) of the target site (e.g., start codon) and (2) the presence of 5′G. The targeting domain for tier 4 gRNA molecules were selected based on distance to a target site (e.g., start codon), e.g., within 500 bp (e.g., downstream) of the target site (e.g., start codon). The targeting domain for tier 5 gRNA molecules were selected based on distance to the target site (e.g., start codon), e.g., within reminder of the coding sequence, e.g., downstream of the first 500 bp 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., start codon), e.g., within 500 bp (e.g., downstream) of the target site (e.g., start codon). The targeting domain for tier 2 gRNA molecules were selected based on distance to the target site (e.g., start codon), e.g., within reminder of the coding sequence, e.g., downstream of the first 500 bp 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 15A-15D), and N. meningitidis (Tables 17A-17B); and 5 tiers for S. aureus (Tables 16A-16D). 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., start codon), e.g., within 500 bp (e.g., downstream) of the target site (e.g., 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., start codon), e.g., within 500 bp (e.g., downstream) of the target site (e.g., 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., start codon), e.g., within reminder of the coding sequence, e.g., downstream of the first 500 bp 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., start codon), e.g., within 500 bp (e.g., downstream) of the target site (e.g., start codon), (2) a high level of orthogonality, and (3) PAM is NNGRRT. The targeting domain 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., start codon), e.g., within 500 bp (e.g., downstream) of the target site (e.g., 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., start codon) mutation, e.g., within 500 bp (e.g., downstream) of the target site (e.g., 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., start codon), e.g., within reminder of the coding sequence, e.g., downstream of the first 500 bp 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., start codon), e.g., within reminder of the coding sequence, e.g., downstream of the first 500 bp 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 500 bp (e.g., downstream) of the target site (e.g., 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., start codon), e.g., within 500 bp (e.g., downstream) of the target site (e.g., 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., start codon), e.g., within reminder of the coding sequence, e.g., downstream of the first 500 bp 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 BCL11A 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 BCL11A target position), or downstream of (e.g., within 500 bp, e.g., within 200 bp downstream of the BCL11A 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 close proximity to the BCL11A 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 BCL11A target position), or downstream of (e.g., within 500 bp, e.g., within 200 bp downstream of the BCL11A target position) in the BCL11A gene.
• In an embodiment, dual targeting is used to create two double strand breaks to in close proximity 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 BCL11A target position), or downstream of (e.g., within 500 bp, e.g., within 200 bp downstream of the BCL11A 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 BCL11A 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 BCL11A target position) in the BCL11A 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 BCL11A 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 BCL11A target position) or downstream of (e.g., within 500 bp, e.g., within 200 bp downstream of the BCL11A 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 BCL11A 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 BCL11A 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 BCL11A target position) in the BCL11A 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 0-50 bp. 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 15D (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 15D (for S. pyogenes). For example, BCL11A-5355 or BCL11A-5380 can be combined with BCL11A-5321 or BCL11A-5416; or BCL11A-5333, BCL11A-5354, or BCL11A-5329 can be combined with BCL11A-5367 or BCL11A-5341.
• Strategies to Identify gRNAs for S. pyogenes, S. aureus, and N. meningitidis to Knock Down the BCL11A Gene
• gRNAs were designed for use with S. pyogenes, S. aureus and N. meningitidis one or more 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 BCL11A 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 BCL11A gene were designed to target the 1 kb of sequence 3′ of the start codon. They were listed in a single list for S. pyogenes (Table 3A), S. aureus (Table 3B) and N. meningitidis (Table 3C).
• In a second strategy, the gRNAs were identified and ranked into 4 tiers for S. pyogenes (Tables 10A-10D), and S. aureus (Tables 11A-11D). The gRNAs were identified and listed in a single list for N. meningitidis (Table 12). 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 500 bp (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 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 500 bp (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 500 bp (e.g., upstream or downstream) of the target site (e.g., the transcription start site) and (2) the presence of 5′G. The targeting domain for tier 4 gRNA molecules were selected based on distance to a target site (e.g., the transcription start site), e.g., within 500 bp (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 18A-18C). 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 500 bp (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 500 bp (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 19A-19B). 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 500 bp (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 500 bp (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 500 bp (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 20A-20C). 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 500 bp (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 500 bp (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 S. pyogenes, S. aureus and N. meningitidis one or more Cas9 molecules.
• In an strategy, the gRNAs were identified and ranked into 4 tiers for S. pyogenes (Tables 7A-7D) and for S. aureus (Tables 8A-8D). The gRNAs were identified and listed in a single list for N. meningitidis (Table 9). 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 51.7 kb downstream of transcription start site, TSS) or 3′ (65.1 to 65.3 kb 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 21A-21E). 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 51.7 kb downstream of TSS) or 3′ (65.1 to 65.3 kb 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 51.7 kb downstream of TSS) or 3′ (65.1 to 65.3 kb 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 51.7 kb downstream of TSS) or 3′ (65.1 to 65.3 kb 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 51.7 kb downstream of TSS) or 3′ (65.1 to 65.3 kb downstream of TSS). The gRNAs were identified and ranked into 5 tiers for S. aureus, when the relevant PAM was NNGRRT or NNGRRV (Tables 22A-22E). 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 51.7 kb downstream of TSS) or 3′ (65.1 to 65.3 kb 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 51.7 kb downstream of TSS) or 3′ (65.1 to 65.3 kb 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 51.7 kb downstream of TSS) or 3′ (65.1 to 65.3 kb 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 51.7 kb downstream of TSS) or 3′ (65.1 to 65.3 kb 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 51.7 kb downstream of TSS) or 3′ (65.1 to 65.3 kb downstream of TSS), and (2) PAM is NNGRRV. The gRNAs were identified and ranked into 3 tiers for N. meningitidis (Tables 23A-23C). 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 51.7 kb downstream of TSS) or 3′ (65.1 to 65.3 kb 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 51.7 kb downstream of TSS) or 3′ (65.1 to 65.3 kb 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 51.7 kb downstream of TSS) or 3′ (65.1 to 65.3 kb 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 51.7 kb downstream of TSS) or 3′ (65.1 to 65.3 kb 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 0-50 bp. 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 20E (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 20E (for S. pyogenes). For example, BCL11A-13271 or BCL11A-13264 can be combined with BCL11A-13276; or BCL11A-13262 or BCL11A-13282 can be combined with BCL11A-13290 or BCL11A-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 the E6V target site in the HBB gene selected according to the first tier parameters, and are selected based on the close proximity and orientation to mutation and orthogonality in the human genome. 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 a Cas9 molecule (e.g., a S. pyogenes Cas9 molecule) that gives double stranded cleavage. 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 0-50 bp. 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. 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., HBB-8 and HBB-25 are used. In an embodiment, two 17-mer RNAs are used to target two Cas9 nucleases or two Cas9 nickases, e.g., HBB-35 and HBB-53 are used.

• TABLE 1A
  			Target	SEQ
  1st Tier	DNA		Site	ID
  gRNA Name	Strand	Targeting Domain	Length	NO
  HBB-8	−	AAGGUGAACGUGGAUGAAGU	20	387
  HBB-25	+	GUAACGGCAGACUUCUCCUC		20	388
  HBB-35	−	GUGAACGUGGAUGAAGU	17	389
  HBB-53	+	ACGGCAGACUUCUCCUC		17	390

• Table 1B provides exemplary targeting domains for the E6V target site in the HBB gene selected according to the second tier parameters and are selected based on the presence of a 5′ G and reasonable proximity to mutation. 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 a S. pyogenes Cas9 molecule that gives double stranded cleavage. Any of the targeting domains in the table can be used with S. pyogenes single-stranded 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 1B
  			Target	SEQ
  2nd Tier	DNA		Site	ID
  gRNA Name	Strand	Targeting Domain	Length	NO
  HBB-12	−	GAAGUUGGUGGUGAGGCCCU	20	391
  HBB-1	−	GCAACCUCAAACAGACACCA	20	392
  HBB-52	+	GCCCCACAGGGCAGUAA		17	393
  HBB-32	−	GCCGUUACUGCCCUGUG	17	394
  HBB-46	−	GGAGACCAAUAGAAACU	17	395
  HBB-37	−	GGAUGAAGUUGGUGGUG	17	396
  HBB-29	−	GGUGCAUCUGACUCCUG	17	397
  HBB-4	−	GUCUGCCGUUACUGCCCUGU	20	398
  HBB-9	−	GUGAACGUGGAUGAAGUUGG	20	399
  HBB-34	−	GUGGGGCAAGGUGAACG	17	400
  HBB-40	−	GUGGUGAGGCCCUGGGC	17	401
  HBB-44	−	GUUACAAGACAGGUUUA	17	402
  HBB-51	+	GUUCACCUUGCCCCACA		17	403
  HBB-39	−	GUUGGUGGUGAGGCCCU	17	404

• Table 1C provides exemplary targeting domains for the E6V target site in the HBB gene selected according to the third tier parameters and are selected based on reasonable proximity to mutation. 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 a S. pyogenes Cas9 molecule that gives double stranded cleavage. Any of the targeting domains in the table can be used with S. pyogenes single-stranded 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 1C
  			Target	SEQ
  3rd Tier	DNA		Site	ID
  gRNA Name	Strand	Targeting Domain	Length	NO
  HBB-36	−	AACGUGGAUGAAGUUGG	17	405
  HBB-17	−	AAGGUUACAAGACAGGUUUA	20	406
  HBB-47	+	ACAUGCCCAGUUUCUAU	17	407
  HBB-55	+	ACCAUGGUGUCUGUUUG	17	408
  HBB-28	−	ACCUCAAACAGACACCA	17	409
  HBB-20	+	ACCUUGAUACCAACCUGCCC	20	410
  HBB-45	−	AGGAGACCAAUAGAAAC	17	411
  HBB-54	+	AGGAGUCAGAUGCACCA	17	412
  HBB-3	−	AGUCUGCCGUUACUGCCCUG	20	413
  HBB-38	−	AGUUGGUGGUGAGGCCC	17	414
  HBB-23	+	CACGUUCACCUUGCCCCACA	20	415
  HBB-2	−	CAUGGUGCAUCUGACUCCUG	20	416
  HBB-22	+	CCACGUUCACCUUGCCCCAC	20	417
  HBB-15	−	CCCUGGGCAGGUUGGUAUCA	20	418
  HBB-7	−	CCUGUGGGGCAAGGUGAACG	20	419
  HBB-21	+	CCUUGAUACCAACCUGCCCA	20	420
  HBB-10	−	CGUGGAUGAAGUUGGUGGUG	20	421
  HBB-6	−	CGUUACUGCCCUGUGGGGCA	20	422
  HBB-50	+	CGUUCACCUUGCCCCAC	17	423
  HBB-26	+	CUCAGGAGUCAGAUGCACCA	20	424
  HBB-30	−	CUGCCGUUACUGCCCUG	17	425
  HBB-24	+	CUUGCCCCACAGGGCAGUAA	20	426
  HBB-19	−	UAAGGAGACCAAUAGAAACU	20	427
  HBB-33	−	UACUGCCCUGUGGGGCA	17	428
  HBB-43	−	UAUCAAGGUUACAAGAC	17	429
  HBB-5	−	UCUGCCGUUACUGCCCUGUG	20	430
  HBB-11	−	UGAAGUUGGUGGUGAGGCCC	20	431
  HBB-41	−	UGAGGCCCUGGGCAGGU	17	432
  HBB-49	+	UGAUACCAACCUGCCCA	17	433
  HBB-27	+	UGCACCAUGGUGUCUGUUUG	20	434
  HBB-31	−	UGCCGUUACUGCCCUGU	17	435
  HBB-42	−	UGGGCAGGUUGGUAUCA	17	436
  HBB-16	−	UGGUAUCAAGGUUACAAGAC	20	437
  HBB-14	−	UGGUGAGGCCCUGGGCAGGU	20	438
  HBB-18	−	UUAAGGAGACCAAUAGAAAC	20	439
  HBB-48	+	UUGAUACCAACCUGCCC	17	440
  HBB-13	−	UUGGUGGUGAGGCCCUGGGC	20	441

• Table 1D provides exemplary targeting domains for the E6V target site in the HBB gene selected based on close proximity to mutation. 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 a S. aureus Cas9 molecule that gives double stranded cleavage. Any of the targeting domains in the table can be used with S. aureus single-stranded 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 ID
  			Target	SEQ
  	DNA		Site	ID
  gRNA Name	Strand	Targeting Domain	Length	NO
  HBB-56	−	CACCAUGGUGCAUCUGACUC	20	442
  HBB-57	−	CCAUGGUGCAUCUGACUCCU	20	443
  HBB-58	−	CAUGGUGCAUCUGACUCCUG	20	444
  HBB-59	−	UGGUGCAUCUGACUCCUGAG	20	445
  HBB-60	−	AAGUCUGCCGUUACUGCCCU	20	446
  HBB-61	−	AGUCUGCCGUUACUGCCCUG	20	447
  HBB-62	−	UUACUGCCCUGUGGGGCAAG	20	448
  HBB-63	−	CCCUGUGGGGCAAGGUGAAC	20	449
  HBB-64	−	GUGGGGCAAGGUGAACGUGG	20	450
  HBB-65	−	GAACGUGGAUGAAGUUGGUG	20	451
  HBB-66	−	AUGAAGUUGGUGGUGAGGCC	20	452
  HBB-67	−	CAAGGUUACAAGACAGGUUU	20	453
  HBB-68	−	AAGGUUACAAGACAGGUUUA	20	454
  HBB-69	−	GACAGGUUUAAGGAGACCAA	20	455
  HBB-70	−	UUUAAGGAGACCAAUAGAAA	20	456
  HBB-71	−	CAUGGUGCAUCUGACUC	20	457
  HBB-72	−	UGGUGCAUCUGACUCCU	17	458
  HBB-73	−	GGUGCAUCUGACUCCUG	17	459
  HBB-74	−	UGCAUCUGACUCCUGAG	17	460
  HBB-75	−	UCUGCCGUUACUGCCCU	17	461
  HBB-76	−	CUGCCGUUACUGCCCUG	17	462
  HBB-77	−	CUGCCCUGUGGGGCAAG	17	463
  HBB-78	−	UGUGGGGCAAGGUGAAC	17	464
  HBB-79	−	GGGCAAGGUGAACGUGG	17	465
  HBB-80	−	CGUGGAUGAAGUUGGUG	17	466
  HBB-81	−	AAGUUGGUGGUGAGGCC	17	467
  HBB-82	−	GGUUACAAGACAGGUUU	17	468
  HBB-83	−	GUUACAAGACAGGUUUA	17	469
  HBB-84	−	AGGUUUAAGGAGACCAA	17	470
  HBB-85	−	AAGGAGACCAAUAGAAA	17	471
  HBB-86	+	GCUAGUGAACACAGUUGUGU	20	472
  HBB-87	+	GUGUCUGUUUGAGGUUGCUA	20	473
  HBB-88	+	AGAUGCACCAUGGUGUCUGU	20	474
  HBB-89	+	GUAACGGCAGACUUCUCCUC	20	475
  HBB-90	+	AGUAACGGCAGACUUCUCCU	20	476
  HBB-91	+	UCCACGUUCACCUUGCCCCA	20	477
  HBB-92	+	AACCUUGAUACCAACCUGCC	20	478
  HBB-93	+	AGUGAACACAGUUGUGU	17	479
  HBB-94	+	UCUGUUUGAGGUUGCUA	17	480
  HBB-95	+	UGCACCAUGGUGUCUGU	17	481
  HBB-96	+	ACGGCAGACUUCUCCUC	17	482
  HBB-97	+	AACGGCAGACUUCUCCU	17	483
  HBB-98	+	ACGUUCACCUUGCCCCA	17	484
  HBB-99	+	CUUGAUACCAACCUGCC	17	485

• Table 2A provides exemplary targeting domains for knocking out the BCL11A gene selected according to first tier parameters, and are selected based on close proximity to start of the coding sequence and orthogonality in the human genome. 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 a S. pyogenes Cas9 molecule that gives double stranded cleavage. Any of the targeting domains in the table can be used with a S. pyogenes Cas9 single-stranded break nucleases (nickases). In an embodiment, dual targeting is used to create two nicks. 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. In an embodiment, two 20-mer guide RNAs are used to target two S. pyogenes Cas9 nucleases or two S. pyogenes Cas9 nickases, e.g., BCL11A-31 and BCL11A-40, BCL11A-30 and BCL11A-42, or BCL11A-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., BCL11A-79 and BCL11A-90, BCL11A-77 and BCL11A-92, or BCL11A-71 and BCL11A-103 are used.

• TABLE 2A
  1st Tier

  	DNA		Target Site	SEQ ID
  gRNA Name	Strand	Targeting Domain	Length	NO
  BCL11A-32	-	UGGCAUCCAGGUCACGCCAG	20	486
  BCL11A-40	+	GAUGCUUUUUUCAUCUCGAU		20	487
  BCL11A-30	-	GCAUCCAAUCCCGUGGAGGU	20	488
  BCL11A-42	+	UUUUCAUCUCGAUUGGUGAA		20	489
  BCL11A-24	-	CCAGAUGAACUUCCCAUUGG	20	490
  BCL11A-53	+	AGGAGGUCAUGAUCCCCUUC		20	491
  BCL11A-79	-	CAUCCAGGUCACGCCAG	17	492
  BCL11A-90	+	GCUUUUUUCAUCUCGAU		17	493
  BCL11A-77	-	UCCAAUCCCGUGGAGGU	17	494
  BCL11A-92	+	UCAUCUCGAUUGGUGAA		17	495
  BCL11A-71	-	GAUGAACUUCCCAUUGG	17	496
  BCL11A-103	+	AGGUCAUGAUCCCCUUC		17	497

• Table 2B provides exemplary targeting domains for knocking out the BCL11A gene selected according to the second tier parameters and are selected based on close proximity to start of the coding sequence and presence of a 5′ G. 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 a S. pyogenes Cas9 molecule that gives double stranded cleavage. Any of the targeting domains in the table can be used with a S. pyogenes Cas9 single-stranded break nucleases (nickases). In an embodiment, dual targeting is used to create two nicks. 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 2B
  2nd Tier

  	DNA		Target Site	SEQ ID
  gRNA Name	Strand	Targeting Domain	Length	NO
  BCL11A-28	-	GAAAAAAGCAUCCAAUCCCG	20	498
  BCL11A-15	-	GAACCAGACCACGGCCCGUU	20	499
  BCL11A-37	+	GACCUGGAUGCCAACCUCCA		20	500
  BCL11A-120	+	GAGCUCCAUGUGCAGAACGA		20	501
  BCL11A-106	+	GAGCUCCCAACGGGCCG		17	502
  BCL11A-112	-	GAGCUCUAAUCCCCACGCCU	20	503
  BCL11A-113	-	GAGUGCAGAAUAUGCCCCGC	20	504
  BCL11A-35	+	GAUAAACAAUCGUCAUCCUC		20	505
  BCL11A-19	-	GAUCAUGACCUCCUCACCUG	20	506
  BCL11A-60	-	GAUGAUGAACCAGACCA	17	507
  BCL11A-39	+	GAUGCCAACCUCCACGGGAU		20	508
  BCL11A-133	+	GCACUCAUCCCAGGCGU		17	509
  BCL11A-130	-	GCAGAAUAUGCCCCGCA	17	510
  BCL11A-115	+	GCAUAUUCUGCACUCAUCCC		20	511
  BCL11A-89	+	GCCAACCUCCACGGGAU		17	512
  BCL11A-23	-	GCCAGAUGAACUUCCCAUUG	20	513
  BCL11A-17	-	GCCCGUUGGGAGCUCCAGAA	20	514
  BCL11A-83	+	GCUAUGUGUUCCUGUUU		17	515
  BCL11A-135	+	GCUCCAUGUGCAGAACG		17	516
  BCL11A-57	+	GCUCCCAACGGGCCGUGGUC		20	517
  BCL11A-127	-	GCUCUAAUCCCCACGCC	17	518
  BCL11A-6	+	GCUGGGGUUUGCCUUGCUUG		20	519
  BCL11A-111	-	GGAGCUCUAAUCCCCACGCC	20	520
  BCL11A-101	+	GGCACUGCCCACAGGUG		17	521
  BCL11A-52	+	GGCACUGCCCACAGGUGAGG		20	522
  BCL11A-16	-	GGCCCGUUGGGAGCUCCAGA	20	523
  BCL11A-12	+	GGGGUUUGCCUUGCUUG		17	524
  BCL11A-109	+	GUAAGAAUGGCUUCAAG		17	525
  BCL11A-123	+	GUGCAGAACGAGGGGAGGAG		20	526
  BCL11A-21	-	GUGCCAGAUGAACUUCCCAU	20	527
  BCL11A-50	+	GUUCAUCUGGCACUGCCCAC		20	528
  BCL11A-65	-	GUUGGGAGCUCCAGAAG	17	529

• Table 2C provides exemplary targeting domains for knocking out the BCL11A gene selected according to the third tier parameters and are selected based on close proximity to start of the coding sequence. 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 a S. pyogenes Cas9 molecule that gives double stranded cleavage. Any of the targeting domains in the table can be used with a S. pyogenes Cas9 single-stranded break nucleases (nickases). In an embodiment, dual targeting is used to create two nicks. 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 2C
  3rd Tier

  	DNA		Target Site	SEQ ID
  gRNA Name	Strand	Targeting Domain	Length	NO
  BCL11A-75	-	AAAAGCAUCCAAUCCCG	17	530
  BCL11A-29	-	AAAAGCAUCCAAUCCCGUGG	20	531
  BCL11A-47	+	AAAAUAAGAAUGUCCCCCAA	20	532
  BCL11A-85	+	AAACAAUCGUCAUCCUC	17	533
  BCL11A-73	-	AAACGGAAACAAUGCAA	17	534
  BCL11A-125	-	AAACUUCUGCACUGGAG	17	535
  BCL11A-48	+	AAAUAAGAAUGUCCCCCAAU	20	536
  BCL11A-1	-	AACCCCAGCACUUAAGCAAA	20	537
  BCL11A-13	-	ACAGAUGAUGAACCAGACCA	20	538
  BCL11A-61	-	ACCAGACCACGGCCCGU	17	539
  BCL11A-2	-	ACCCCAGCACUUAAGCAAAC	20	540
  BCL11A-38	+	ACCUGGAUGCCAACCUCCAC	20	541
  BCL11A-102	+	ACUGCCCACAGGUGAGG	17	542
  BCL11A-119	+	AGAGCUCCAUGUGCAGAACG	20	543
  BCL11A-70	-	AGAUGAACUUCCCAUUG	17	544
  BCL11A-76	-	AGCAUCCAAUCCCGUGG	17	545
  BCL11A-121	+	AGCUCCAUGUGCAGAACGAG	20	546
  BCL11A-81	-	AGGAAUUUGCCCCAAAC	17	547
  BCL11A-114	-	AGUGCAGAAUAUGCCCCGCA	20	548
  BCL11A-97	+	AUAAGAAUGUCCCCCAA	17	549
  BCL11A-20	-	AUCAUGACCUCCUCACCUGU	20	550
  BCL11A-44	+	AUCUCGAUUGGUGAAGGGGA	20	551
  BCL11A-67	-	AUGACCUCCUCACCUGU	17	552
  BCL11A-138	+	AUGUGCAGAACGAGGGG	17	553
  BCL11A-3	+	AUUCCCGUUUGCUUAAGUGC	20	554
  BCL11A-95	+	AUUGGUGAAGGGGAAGG	17	555
  BCL11A-26	-	CACAAACGGAAACAAUGCAA	20	556
  BCL11A-134	+	CACUCAUCCCAGGCGUG	17	557
  BCL11A-139	+	CAGAACGAGGGGAGGAG	17	558
  BCL11A-69	-	CAGAUGAACUUCCCAUU	17	559
  BCL11A-96	+	CAGCUUUUUCUAAGCAG	17	560
  BCL11A-86	+	CAUCCUCUGGCGUGACC	17	561
  BCL11A-93	+	CAUCUCGAUUGGUGAAG	17	562
  BCL11A-100	+	CAUCUGGCACUGCCCAC	17	563
  BCL11A-66	-	CAUGACCUCCUCACCUG	17	564
  BCL11A-99	+	CCAAUGGGAAGUUCAUC	17	565
  BCL11A-46	+	CCACAGCUUUUUCUAAGCAG	20	566
  BCL11A-62	-	CCAGACCACGGCCCGUU	17	567
  BCL11A-68	-	CCAGAUGAACUUCCCAU	17	568
  BCL11A-8	-	CCAGCACUUAAGCAAAC	17	569
  BCL11A-107	+	CCCAACGGGCCGUGGUC	17	570
  BCL11A-7	-	CCCAGCACUUAAGCAAA	17	571
  BCL11A-49	+	CCCCCAAUGGGAAGUUCAUC	20	572
  BCL11A-55	+	CCCCUUCUGGAGCUCCCAAC	20	573
  BCL11A-18	-	CCCGUUGGGAGCUCCAGAAG	20	574
  BCL11A-9	+	CCCGUUUGCUUAAGUGC	17	575
  BCL11A-63	-	CCGUUGGGAGCUCCAGA	17	576
  BCL11A-10	+	CCGUUUGCUUAAGUGCU	17	577
  BCL11A-27	-	CCUCUGCUUAGAAAAAGCUG	20	578
  BCL11A-104	+	CCUUCUGGAGCUCCCAA	17	579
  BCL11A-36	+	CGUCAUCCUCUGGCGUGACC	20	580
  BCL11A-78	-	CGUGGAGGUUGGCAUCC	17	581
  BCL11A-64	-	CGUUGGGAGCUCCAGAA	17	582
  BCL11A-11	+	CGUUUGCUUAAGUGCUG	17	583
  BCL11A-84	+	CUAUGUGUUCCUGUUUG	17	584
  BCL11A-136	+	CUCCAUGUGCAGAACGA	17	585
  BCL11A-128	-	CUCUAAUCCCCACGCCU	17	586
  BCL11A-118	+	CUGCACUCAUCCCAGGCGUG	20	587
  BCL11A-74	-	CUGCUUAGAAAAAGCUG	17	588
  BCL11A-56	+	CUGGAGCUCCCAACGGGCCG	20	589
  BCL11A-87	+	CUGGAUGCCAACCUCCA	17	590
  BCL11A-105	+	CUUCUGGAGCUCCCAAC	17	591
  BCL11A-124	-	UAAACUUCUGCACUGGA	17	592
  BCL11A-98	+	UAAGAAUGUCCCCCAAU	17	593
  BCL11A-34	-	UAGAGGAAUUUGCCCCAAAC	20	594
  BCL11A-131	+	UAUUCUGCACUCAUCCC	17	595
  BCL11A-137	+	UCCAUGUGCAGAACGAG	17	596
  BCL11A-122	+	UCCAUGUGCAGAACGAGGGG	20	597
  BCL11A-126	-	UCCCCUCGUUCUGCACA	17	598
  BCL11A-54	+	UCCCCUUCUGGAGCUCCCAA	20	599
  BCL11A-31	-	UCCCGUGGAGGUUGGCAUCC	20	600
  BCL11A-5	+	UCCCGUUUGCUUAAGUGCUG	20	601
  BCL11A-110	-	UCCUCCCCUCGUUCUGCACA	20	602
  BCL11A-94	+	UCGAUUGGUGAAGGGGA	17	603
  BCL11A-45	+	UCGAUUGGUGAAGGGGAAGG	20	604
  BCL11A-117	+	UCUGCACUCAUCCCAGGCGU	20	605
  BCL11A-51	+	UCUGGCACUGCCCACAGGUG	20	606
  BCL11A-59	+	UCUGUAAGAAUGGCUUCAAG	20	607
  BCL11A-14	-	UGAACCAGACCACGGCCCGU	20	608
  BCL11A-132	+	UGCACUCAUCCCAGGCG	17	609
  BCL11A-129	-	UGCAGAAUAUGCCCCGC	17	610
  BCL11A-22	-	UGCCAGAUGAACUUCCCAUU	20	611
  BCL11A-82	+	UGCUAUGUGUUCCUGUU	17	612
  BCL11A-88	+	UGGAUGCCAACCUCCAC	17	613
  BCL11A-58	+	UGGUUCAUCAUCUGUAAGAA	20	614
  BCL11A-33	-	UGUUUAUCAACGUCAUCUAG	20	615
  BCL11A-80	-	UUAUCAACGUCAUCUAG	17	616
  BCL11A-25	-	UUAUUUUUAUCGAGCACAAA	20	617
  BCL11A-108	+	UUCAUCAUCUGUAAGAA	17	618
  BCL11A-91	+	UUCAUCUCGAUUGGUGA	17	619
  BCL11A-4	+	UUCCCGUUUGCUUAAGUGCU	20	620
  BCL11A-116	+	UUCUGCACUCAUCCCAGGCG	20	621
  BCL11A-43	+	UUUCAUCUCGAUUGGUGAAG	20	622
  BCL11A-72	-	UUUUUAUCGAGCACAAA	17	623
  BCL11A-41	+	UUUUUCAUCUCGAUUGGUGA	20	624

• Table 2D) provides exemplary targeting domains for knocking out the BCL11A gene selected according to the fourth tier parameters and are selected based on presence in the coding sequence. 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 a S. pyogenes Cas9 molecule that gives double stranded cleavage. Any of the targeting domains in the table can be used with a S. pyogenes Cas9 single-stranded break nucleases (nickases). In an embodiment, dual targeting is used to create two nicks. 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 2D
  4th Tier

  	DNA		Target Site	SEQ ID
  gRNA Name	Strand	Targeting domain	Length	NO

  BCL11A-140	-	AACAGCCAUUCACCAGUGCA	20	625
  BCL11A-141	-	CAACACGCACAGAACACUCA	20	626
  BCL11A-142	-	AUCUACUUAGAAAGCGAACA	20	627
  BCL11A-143	-	ACGGAAGUCCCCUGACCCCG	20	628
  BCL11A-144	-	CGGAAGUCCCCUGACCCCGC	20	629
  BCL11A-145	-	AGUCCCCUGACCCCGCGGGU	20	630
  BCL11A-146	-	CCGCGGGUUGGUAUCCCUUC	20	631
  BCL11A-147	-	GUUGGUAUCCCUUCAGGACU	20	632
  BCL11A-148	-	CCUUCCCAGCCACCUCUCCA	20	633
  BCL11A-149	-	CUUCCCAGCCACCUCUCCAU	20	634
  BCL11A-150	-	UUUAACCUGCUAAGAAUACC	20	635
  BCL11A-151	-	ACCAGGAUCAGUAUCGAGAG	20	636
  BCL11A-152	-	UCAGUAUCGAGAGAGGCUUC	20	637
  BCL11A-153	-	AUCGAGAGAGGCUUCCGGCC	20	638
  BCL11A-154	-	GAGGCUUCCGGCCUGGCAGA	20	639
  BCL11A-155	-	AGGCUUCCGGCCUGGCAGAA	20	640
  BCL11A-156	-	UCCACCACCGAGACAUCACU	20	641
  BCL11A-157	-	CCCCCACCGCAUAGAGCGCC	20	642
  BCL11A-158	-	CCCCACCGCAUAGAGCGCCU	20	643
  BCL11A-159	-	CCCACCGCAUAGAGCGCCUG	20	644
  BCL11A-160	-	CCACCGCAUAGAGCGCCUGG	20	645
  BCL11A-161	-	CCGCAUAGAGCGCCUGGGGG	20	646
  BCL11A-162	-	GCGCCUGGGGGCGGAAGAGA	20	647
  BCL11A-163	-	GGGGGCGGAAGAGAUGGCCC	20	648
  BCL11A-164	-	AUCACCCGAGUGCCUUUGAC	20	649
  BCL11A-165	-	UCACCCGAGUGCCUUUGACA	20	650
  BCL11A-166	-	GUGCCUUUGACAGGGUGCUG	20	651
  BCL11A-167	-	GGUGCUGCGGUUGAAUCCAA	20	652
  BCL11A-168	-	GCGGUUGAAUCCAAUGGCUA	20	653
  BCL11A-169	-	GGCUAUGGAGCCUCCCGCCA	20	654
  BCL11A-170	-	CUCCCGCCAUGGAUUUCUCU	20	655
  BCL11A-171	-	CUCUAGGAGACUUAGAGAGC	20	656
  BCL11A-172	-	AGGAGACUUAGAGAGCUGGC	20	657
  BCL11A-173	-	GGAGACUUAGAGAGCUGGCA	20	658
  BCL11A-174	-	UCUAGCCCACCGCUGUCCCC	20	659
  BCL11A-175	-	GCCCACCGCUGUCCCCAGGC	20	660
  BCL11A-176	-	GCCGGCCCAGCCCUAUGCAA	20	661
  BCL11A-177	-	UUACUGCAACCAUUCCAGCC	20	662
  BCL11A-178	-	AGGUAGCAAGCCGCCCUUCC	20	663
  BCL11A-179	-	CCCUCCUCCCUCCCAGCCCC	20	664
  BCL11A-180	-	UCCAAGUCAUGCGAGUUCUG	20	665
  BCL11A-181	-	GUUCAAAUUUCAGAGCAACC	20	666
  BCL11A-182	-	CAAAUUUCAGAGCAACCUGG	20	667
  BCL11A-183	-	AGAGCAACCUGGUGGUGCAC	20	668
  BCL11A-184	-	GGUGCACCGGCGCAGCCACA	20	669
  BCL11A-185	-	GUGCACCGGCGCAGCCACAC	20	670
  BCL11A-186	-	GUGCGACCACGCGUGCACCC	20	671
  BCL11A-187	-	GCACAAAUCGUCCCCCAUGA	20	672
  BCL11A-188	-	AUGACGGUCAAGUCCGACGA	20	673
  BCL11A-189	-	UCUCUCCACCGCCAGCUCCC	20	674
  BCL11A-190	-	ACCGCCAGCUCCCCGGAACC	20	675
  BCL11A-191	-	GGAACCCGGCACCAGCGACU	20	676
  BCL11A-192	-	ACCCGGCACCAGCGACUUGG	20	677
  BCL11A-193	-	CCCGGCACCAGCGACUUGGU	20	678
  BCL11A-194	-	CAGCAGCGCGCUCAAGUCCG	20	679
  BCL11A-195	-	CAGCGCGCUCAAGUCCGUGG	20	680
  BCL11A-196	-	GAACGACCCCAACCUGAUCC	20	681
  BCL11A-197	-	CCCAACCUGAUCCCGGAGAA	20	682
  BCL11A-198	-	CCAACCUGAUCCCGGAGAAC	20	683
  BCL11A-199	-	CAACCUGAUCCCGGAGAACG	20	684
  BCL11A-200	-	GAUCCCGGAGAACGGGGACG	20	685
  BCL11A-201	-	CCCGGAGAACGGGGACGAGG	20	686
  BCL11A-202	-	GAACGGGGACGAGGAGGAAG	20	687
  BCL11A-203	-	CGGGGACGAGGAGGAAGAGG	20	688
  BCL11A-204	-	GGAGGAAGAGGAGGACGACG	20	689
  BCL11A-205	-	AGAGGAGGACGACGAGGAAG	20	690
  BCL11A-206	-	CGACGAGGAAGAGGAAGAAG	20	691
  BCL11A-207	-	CGAGGAAGAGGAAGAAGAGG	20	692
  BCL11A-208	-	AGAGGAAGAAGAGGAGGAAG	20	693
  BCL11A-209	-	GGAAGAAGAGGAGGAAGAGG	20	694
  BCL11A-210	-	AGAAGAGGAGGAAGAGGAGG	20	695
  BCL11A-211	-	AGAGGAGGAAGAGGAGGAGG	20	696
  BCL11A-212	+	UCCUCCUCGUCCCCGUUCUC	20	697
  BCL11A-213	+	CCUCCUCGUCCCCGUUCUCC	20	698
  BCL11A-214	+	CGUCCCCGUUCUCCGGGAUC	20	699
  BCL11A-215	+	CCCGUUCUCCGGGAUCAGGU	20	700
  BCL11A-216	+	CCGUUCUCCGGGAUCAGGUU	20	701
  BCL11A-217	+	CGUUCUCCGGGAUCAGGUUG	20	702
  BCL11A-218	+	GUCGUUCUCGCUCUUGAACU	20	703
  BCL11A-219	+	GCUCUUGAACUUGGCCACCA	20	704
  BCL11A-220	+	CACGGACUUGAGCGCGCUGC	20	705
  BCL11A-221	+	GGCGCUGCCCACCAAGUCGC	20	706
  BCL11A-222	+	GCCCACCAAGUCGCUGGUGC	20	707
  BCL11A-223	+	CCCACCAAGUCGCUGGUGCC	20	708
  BCL11A-224	+	AAGUCGCUGGUGCCGGGUUC	20	709
  BCL11A-225	+	AGUCGCUGGUGCCGGGUUCC	20	710
  BCL11A-226	+	GUCGCUGGUGCCGGGUUCCG	20	711
  BCL11A-227	+	GGUGCCGGGUUCCGGGGAGC	20	712
  BCL11A-228	+	GCCGGGUUCCGGGGAGCUGG	20	713
  BCL11A-229	+	GGGUUCCGGGGAGCUGGCGG	20	714
  BCL11A-230	+	GGCGGUGGAGAGACCGUCGU	20	715
  BCL11A-231	+	GUCGUCGGACUUGACCGUCA	20	716
  BCL11A-232	+	UCGUCGGACUUGACCGUCAU	20	717
  BCL11A-233	+	CGUCGGACUUGACCGUCAUG	20	718
  BCL11A-234	+	GUCGGACUUGACCGUCAUGG	20	719
  BCL11A-235	+	UGUGCAUGUGCGUCUUCAUG	20	720
  BCL11A-236	+	CAUGUGGCGCUUCAGCUUGC	20	721
  BCL11A-237	+	GGCGCUUCAGCUUGCUGGCC	20	722
  BCL11A-238	+	GCGCUUCAGCUUGCUGGCCU	20	723
  BCL11A-239	+	UGCUGGCCUGGGUGCACGCG	20	724
  BCL11A-240	+	GGGUGCACGCGUGGUCGCAC	20	725
  BCL11A-241	+	GUCGCACAGGUUGCACUUGU	20	726
  BCL11A-242	+	UCGCACAGGUUGCACUUGUA	20	727
  BCL11A-243	+	UGUAGGGCUUCUCGCCCGUG	20	728
  BCL11A-244	+	UCUCGCCCGUGUGGCUGCGC	20	729
  BCL11A-245	+	GGCUGCGCCGGUGCACCACC	20	730
  BCL11A-246	+	GCCGCAGAACUCGCAUGACU	20	731
  BCL11A-247	+	UCGCAUGACUUGGACUUGAC	20	732
  BCL11A-248	+	CGCAUGACUUGGACUUGACC	20	733
  BCL11A-249	+	GCAUGACUUGGACUUGACCG	20	734
  BCL11A-250	+	CAUGACUUGGACUUGACCGG	20	735
  BCL11A-251	+	ACUUGGACUUGACCGGGGGC	20	736
  BCL11A-252	+	CUUGGACUUGACCGGGGGCU	20	737
  BCL11A-253	+	GGACUUGACCGGGGGCUGGG	20	738
  BCL11A-254	+	GACUUGACCGGGGGCUGGGA	20	739
  BCL11A-255	+	UUGACCGGGGGCUGGGAGGG	20	740
  BCL11A-256	+	ACCGGGGGCUGGGAGGGAGG	20	741
  BCL11A-257	+	CCGGGGGCUGGGAGGGAGGA	20	742
  BCL11A-258	+	CGGGGGCUGGGAGGGAGGAG	20	743
  BCL11A-259	+	GGGCUGGGAGGGAGGAGGGG	20	744
  BCL11A-260	+	GGAGGAGGGGCGGAUUGCAG	20	745
  BCL11A-261	+	GGAGGGGCGGAUUGCAGAGG	20	746
  BCL11A-262	+	GAGGGGCGGAUUGCAGAGGA	20	747
  BCL11A-263	+	GGGCGGAUUGCAGAGGAGGG	20	748
  BCL11A-264	+	GGCGGAUUGCAGAGGAGGGA	20	749
  BCL11A-265	+	GCGGAUUGCAGAGGAGGGAG	20	750
  BCL11A-266	+	CGGAUUGCAGAGGAGGGAGG	20	751
  BCL11A-267	+	GGAUUGCAGAGGAGGGAGGG	20	752
  BCL11A-268	+	GAUUGCAGAGGAGGGAGGGG	20	753
  BCL11A-269	+	GAGGGAGGGGGGGCGUCGCC	20	754
  BCL11A-270	+	GAGGGGGGGCGUCGCCAGGA	20	755
  BCL11A-271	+	AGGGGGGGCGUCGCCAGGAA	20	756
  BCL11A-272	+	GGGGGCGUCGCCAGGAAGGG	20	757
  BCL11A-273	+	AGGAAGGGCGGCUUGCUACC	20	758
  BCL11A-274	+	AGGGCGGCUUGCUACCUGGC	20	759
  BCL11A-275	+	GGCUUGCUACCUGGCUGGAA	20	760
  BCL11A-276	+	GGUUGCAGUAACCUUUGCAU	20	761
  BCL11A-277	+	GUUGCAGUAACCUUUGCAUA	20	762
  BCL11A-278	+	CAGUAACCUUUGCAUAGGGC	20	763
  BCL11A-279	+	AGUAACCUUUGCAUAGGGCU	20	764
  BCL11A-280	+	ACCUUUGCAUAGGGCUGGGC	20	765
  BCL11A-281	+	UGCAUAGGGCUGGGCCGGCC	20	766
  BCL11A-282	+	GCAUAGGGCUGGGCCGGCCU	20	767
  BCL11A-283	+	CAUAGGGCUGGGCCGGCCUG	20	768
  BCL11A-284	+	CUGGGCCGGCCUGGGGACAG	20	769
  BCL11A-285	+	GGCCGGCCUGGGGACAGCGG	20	770
  BCL11A-286	+	GCCGGCCUGGGGACAGCGGU	20	771
  BCL11A-287	+	AAGUCUCCUAGAGAAAUCCA	20	772
  BCL11A-288	+	UCUCCUAGAGAAAUCCAUGG	20	773
  BCL11A-289	+	CUCCUAGAGAAAUCCAUGGC	20	774
  BCL11A-290	+	CUAGAGAAAUCCAUGGCGGG	20	775
  BCL11A-291	+	GCGGGAGGCUCCAUAGCCAU	20	776
  BCL11A-292	+	CAACCGCAGCACCCUGUCAA	20	777
  BCL11A-293	+	AGCACCCUGUCAAAGGCACU	20	778
  BCL11A-294	+	GCACCCUGUCAAAGGCACUC	20	779
  BCL11A-295	+	UGUCAAAGGCACUCGGGUGA	20	780
  BCL11A-296	+	GUCAAAGGCACUCGGGUGAU	20	781
  BCL11A-297	+	AAAGGCACUCGGGUGAUGGG	20	782
  BCL11A-298	+	CACUCGGGUGAUGGGUGGCC	20	783
  BCL11A-299	+	ACUCGGGUGAUGGGUGGCCA	20	784
  BCL11A-300	+	GGGCCAUCUCUUCCGCCCCC	20	785
  BCL11A-301	+	CCGCCCCCAGGCGCUCUAUG	20	786
  BCL11A-302	+	CCCCCAGGCGCUCUAUGCGG	20	787
  BCL11A-303	+	CCCCAGGCGCUCUAUGCGGU	20	788
  BCL11A-304	+	CCCAGGCGCUCUAUGCGGUG	20	789
  BCL11A-305	+	CCAGGCGCUCUAUGCGGUGG	20	790
  BCL11A-306	+	UGGGGGUCCAAGUGAUGUCU	20	791
  BCL11A-307	+	GGGUCCAAGUGAUGUCUCGG	20	792
  BCL11A-308	+	UCCAAGUGAUGUCUCGGUGG	20	793
  BCL11A-309	+	GUCUCGGUGGUGGACUAAAC	20	794
  BCL11A-310	+	UCUCGGUGGUGGACUAAACA	20	795
  BCL11A-311	+	CUCGGUGGUGGACUAAACAG	20	796
  BCL11A-312	+	UCGGUGGUGGACUAAACAGG	20	797
  BCL11A-313	+	CGGUGGUGGACUAAACAGGG	20	798
  BCL11A-314	+	GGUGGUGGACUAAACAGGGG	20	799
  BCL11A-315	+	UGGACUAAACAGGGGGGGAG	20	800
  BCL11A-316	+	GGACUAAACAGGGGGGGAGU	20	801
  BCL11A-317	+	CUAAACAGGGGGGGAGUGGG	20	802
  BCL11A-318	+	GUGGAAAGCGCCCUUCUGCC	20	803
  BCL11A-319	+	AAAGCGCCCUUCUGCCAGGC	20	804
  BCL11A-320	+	GCCUCUCUCGAUACUGAUCC	20	805
  BCL11A-321	+	CUGAUCCUGGUAUUCUUAGC	20	806
  BCL11A-322	+	UGGUAUUCUUAGCAGGUUAA	20	807
  BCL11A-323	+	GGUAUUCUUAGCAGGUUAAA	20	808
  BCL11A-324	+	GUAUUCUUAGCAGGUUAAAG	20	809
  BCL11A-325	+	UGUCUGCAAUAUGAAUCCCA	20	810
  BCL11A-326	+	GCAAUAUGAAUCCCAUGGAG	20	811
  BCL11A-327	+	AUAUGAAUCCCAUGGAGAGG	20	812
  BCL11A-328	+	GAAUCCCAUGGAGAGGUGGC	20	813
  BCL11A-329	+	AAUCCCAUGGAGAGGUGGCU	20	814
  BCL11A-330	+	CCAUGGAGAGGUGGCUGGGA	20	815
  BCL11A-331	+	CAUUCUGCACCUAGUCCUGA	20	816
  BCL11A-332	+	AUUCUGCACCUAGUCCUGAA	20	817
  BCL11A-333	+	CCUGAAGGGAUACCAACCCG	20	818
  BCL11A-334	+	CUGAAGGGAUACCAACCCGC	20	819
  BCL11A-335	+	UGAAGGGAUACCAACCCGCG	20	820
  BCL11A-336	+	GGAUACCAACCCGCGGGGUC	20	821
  BCL11A-337	+	GAUACCAACCCGCGGGGUCA	20	822
  BCL11A-338	+	AUACCAACCCGCGGGGUCAG	20	823
  BCL11A-339	+	UUGCAAGAGAAACCAUGCAC	20	824
  BCL11A-340	+	AGAAACCAUGCACUGGUGAA	20	825
  BCL11A-341	+	AGUUGUACAUGUGUAGCUGC	20	826
  BCL11A-342	+	GUUGUACAUGUGUAGCUGCU	20	827
  BCL11A-343	-	AGCCAUUCACCAGUGCA	17	828
  BCL11A-344	-	CACGCACAGAACACUCA	17	829
  BCL11A-345	-	UACUUAGAAAGCGAACA	17	830
  BCL11A-346	-	GAAGUCCCCUGACCCCG	17	831
  BCL11A-347	-	AAGUCCCCUGACCCCGC	17	832
  BCL11A-348	-	CCCCUGACCCCGCGGGU	17	833
  BCL11A-349	-	CGGGUUGGUAUCCCUUC	17	834
  BCL11A-350	-	GGUAUCCCUUCAGGACU	17	835
  BCL11A-351	-	UCCCAGCCACCUCUCCA	17	836
  BCL11A-352	-	CCCAGCCACCUCUCCAU	17	837
  BCL11A-353	-	AACCUGCUAAGAAUACC	17	838
  BCL11A-354	-	AGGAUCAGUAUCGAGAG	17	839
  BCL11A-355	-	GUAUCGAGAGAGGCUUC	17	840
  BCL11A-356	-	GAGAGAGGCUUCCGGCC	17	841
  BCL11A-357	-	GCUUCCGGCCUGGCAGA	17	842
  BCL11A-358	-	CUUCCGGCCUGGCAGAA	17	843
  BCL11A-359	-	ACCACCGAGACAUCACU	17	844
  BCL11A-360	-	CCACCGCAUAGAGCGCC	17	845
  BCL11A-361	-	CACCGCAUAGAGCGCCU	17	846
  BCL11A-362	-	ACCGCAUAGAGCGCCUG	17	847
  BCL11A-363	-	CCGCAUAGAGCGCCUGG	17	848
  BCL11A-364	-	CAUAGAGCGCCUGGGGG	17	849
  BCL11A-365	-	CCUGGGGGCGGAAGAGA	17	850
  BCL11A-366	-	GGCGGAAGAGAUGGCCC	17	851
  BCL11A-367	-	ACCCGAGUGCCUUUGAC	17	852
  BCL11A-368	-	CCCGAGUGCCUUUGACA	17	853
  BCL11A-369	-	CCUUUGACAGGGUGCUG	17	854
  BCL11A-370	-	GCUGCGGUUGAAUCCAA	17	855
  BCL11A-371	-	GUUGAAUCCAAUGGCUA	17	856
  BCL11A-372	-	UAUGGAGCCUCCCGCCA	17	857
  BCL11A-373	-	CCGCCAUGGAUUUCUCU	17	858
  BCL11A-374	-	UAGGAGACUUAGAGAGC	17	859
  BCL11A-375	-	AGACUUAGAGAGCUGGC	17	860
  BCL11A-376	-	GACUUAGAGAGCUGGCA	17	861
  BCL11A-377	-	AGCCCACCGCUGUCCCC	17	862
  BCL11A-378	-	CACCGCUGUCCCCAGGC	17	863
  BCL11A-379	-	GGCCCAGCCCUAUGCAA	17	864
  BCL11A-380	-	CUGCAACCAUUCCAGCC	17	865
  BCL11A-381	-	UAGCAAGCCGCCCUUCC	17	866
  BCL11A-382	-	UCCUCCCUCCCAGCCCC	17	867
  BCL11A-383	-	AAGUCAUGCGAGUUCUG	17	868
  BCL11A-384	-	CAAAUUUCAGAGCAACC	17	869
  BCL11A-385	-	AUUUCAGAGCAACCUGG	17	870
  BCL11A-386	-	GCAACCUGGUGGUGCAC	17	871
  BCL11A-387	-	GCACCGGCGCAGCCACA	17	872
  BCL11A-388	-	CACCGGCGCAGCCACAC	17	873
  BCL11A-389	-	CGACCACGCGUGCACCC	17	874
  BCL11A-390	-	CAAAUCGUCCCCCAUGA	17	875
  BCL11A-391	-	ACGGUCAAGUCCGACGA	17	876
  BCL11A-392	-	CUCCACCGCCAGCUCCC	17	877
  BCL11A-393	-	GCCAGCUCCCCGGAACC	17	878
  BCL11A-394	-	ACCCGGCACCAGCGACU	17	879
  BCL11A-395	-	CGGCACCAGCGACUUGG	17	880
  BCL11A-396	-	GGCACCAGCGACUUGGU	17	881
  BCL11A-397	-	CAGCGCGCUCAAGUCCG	17	882
  BCL11A-398	-	CGCGCUCAAGUCCGUGG	17	883
  BCL11A-399	-	CGACCCCAACCUGAUCC	17	884
  BCL11A-400	-	AACCUGAUCCCGGAGAA	17	885
  BCL11A-401	-	ACCUGAUCCCGGAGAAC	17	886
  BCL11A-402	-	CCUGAUCCCGGAGAACG	17	887
  BCL11A-403	-	CCCGGAGAACGGGGACG	17	888
  BCL11A-404	-	GGAGAACGGGGACGAGG	17	889
  BCL11A-405	-	CGGGGACGAGGAGGAAG	17	890
  BCL11A-406	-	GGACGAGGAGGAAGAGG	17	891
  BCL11A-407	-	GGAAGAGGAGGACGACG	17	892
  BCL11A-408	-	GGAGGACGACGAGGAAG	17	893
  BCL11A-409	-	CGAGGAAGAGGAAGAAG	17	894
  BCL11A-410	-	GGAAGAGGAAGAAGAGG	17	895
  BCL11A-411	-	GGAAGAAGAGGAGGAAG	17	896
  BCL11A-412	-	AGAAGAGGAGGAAGAGG	17	897
  BCL11A-413	-	AGAGGAGGAAGAGGAGG	17	898
  BCL11A-414	-	GGAGGAAGAGGAGGAGG	17	899
  BCL11A-415	+	UCCUCGUCCCCGUUCUC	17	900
  BCL11A-416	+	CCUCGUCCCCGUUCUCC	17	901
  BCL11A-417	+	CCCCGUUCUCCGGGAUC	17	902
  BCL11A-418	+	GUUCUCCGGGAUCAGGU	17	903
  BCL11A-419	+	UUCUCCGGGAUCAGGUU	17	904
  BCL11A-420	+	UCUCCGGGAUCAGGUUG	17	905
  BCL11A-421	+	GUUCUCGCUCUUGAACU	17	906
  BCL11A-422	+	CUUGAACUUGGCCACCA	17	907
  BCL11A-423	+	GGACUUGAGCGCGCUGC	17	908
  BCL11A-424	+	GCUGCCCACCAAGUCGC	17	909
  BCL11A-425	+	CACCAAGUCGCUGGUGC	17	910
  BCL11A-426	+	ACCAAGUCGCUGGUGCC	17	911
  BCL11A-427	+	UCGCUGGUGCCGGGUUC	17	912
  BCL11A-428	+	CGCUGGUGCCGGGUUCC	17	913
  BCL11A-429	+	GCUGGUGCCGGGUUCCG	17	914
  BCL11A-430	+	GCCGGGUUCCGGGGAGC	17	915
  BCL11A-431	+	GGGUUCCGGGGAGCUGG	17	916
  BCL11A-432	+	UUCCGGGGAGCUGGCGG	17	917
  BCL11A-433	+	GGUGGAGAGACCGUCGU	17	918
  BCL11A-434	+	GUCGGACUUGACCGUCA	17	919
  BCL11A-435	+	UCGGACUUGACCGUCAU	17	920
  BCL11A-436	+	CGGACUUGACCGUCAUG	17	921
  BCL11A-437	+	GGACUUGACCGUCAUGG	17	922
  BCL11A-438	+	GCAUGUGCGUCUUCAUG	17	923
  BCL11A-439	+	GUGGCGCUUCAGCUUGC	17	924
  BCL11A-440	+	GCUUCAGCUUGCUGGCC	17	925
  BCL11A-441	+	CUUCAGCUUGCUGGCCU	17	926
  BCL11A-442	+	UGGCCUGGGUGCACGCG	17	927
  BCL11A-443	+	UGCACGCGUGGUCGCAC	17	928
  BCL11A-444	+	GCACAGGUUGCACUUGU	17	929
  BCL11A-445	+	CACAGGUUGCACUUGUA	17	930
  BCL11A-446	+	AGGGCUUCUCGCCCGUG	17	931
  BCL11A-447	+	CGCCCGUGUGGCUGCGC	17	932
  BCL11A-448	+	UGCGCCGGUGCACCACC	17	933
  BCL11A-449	+	GCAGAACUCGCAUGACU	17	934
  BCL11A-450	+	CAUGACUUGGACUUGAC	17	935
  BCL11A-451	+	AUGACUUGGACUUGACC	17	936
  BCL11A-452	+	UGACUUGGACUUGACCG	17	937
  BCL11A-453	+	GACUUGGACUUGACCGG	17	938
  BCL11A-454	+	UGGACUUGACCGGGGGC	17	939
  BCL11A-455	+	GGACUUGACCGGGGGCU	17	940
  BCL11A-456	+	CUUGACCGGGGGCUGGG	17	941
  BCL11A-457	+	UUGACCGGGGGCUGGGA	17	942
  BCL11A-458	+	ACCGGGGGCUGGGAGGG	17	943
  BCL11A-459	+	GGGGGCUGGGAGGGAGG	17	944
  BCL11A-460	+	GGGGCUGGGAGGGAGGA	17	945
  BCL11A-461	+	GGGCUGGGAGGGAGGAG	17	946
  BCL11A-462	+	CUGGGAGGGAGGAGGGG	17	947
  BCL11A-463	+	GGAGGGGCGGAUUGCAG	17	948
  BCL11A-464	+	GGGGCGGAUUGCAGAGG	17	949
  BCL11A-465	+	GGGCGGAUUGCAGAGGA	17	950
  BCL11A-466	+	CGGAUUGCAGAGGAGGG	17	951
  BCL11A-467	+	GGAUUGCAGAGGAGGGA	17	952
  BCL11A-468	+	GAUUGCAGAGGAGGGAG	17	953
  BCL11A-469	+	AUUGCAGAGGAGGGAGG	17	954
  BCL11A-470	+	UUGCAGAGGAGGGAGGG	17	955
  BCL11A-471	+	UGCAGAGGAGGGAGGGG	17	956
  BCL11A-472	+	GGAGGGGGGGCGUCGCC	17	957
  BCL11A-473	+	GGGGGGCGUCGCCAGGA	17	958
  BCL11A-474	+	GGGGGCGUCGCCAGGAA	17	959
  BCL11A-475	+	GGCGUCGCCAGGAAGGG	17	960
  BCL11A-476	+	AAGGGCGGCUUGCUACC	17	961
  BCL11A-477	+	GCGGCUUGCUACCUGGC	17	962
  BCL11A-478	+	UUGCUACCUGGCUGGAA	17	963
  BCL11A-479	+	UGCAGUAACCUUUGCAU	17	964
  BCL11A-480	+	GCAGUAACCUUUGCAUA	17	965
  BCL11A-481	+	UAACCUUUGCAUAGGGC	17	966
  BCL11A-482	+	AACCUUUGCAUAGGGCU	17	967
  BCL11A-483	+	UUUGCAUAGGGCUGGGC	17	968
  BCL11A-484	+	AUAGGGCUGGGCCGGCC	17	969
  BCL11A-485	+	UAGGGCUGGGCCGGCCU	17	970
  BCL11A-486	+	AGGGCUGGGCCGGCCUG	17	971
  BCL11A-487	+	GGCCGGCCUGGGGACAG	17	972
  BCL11A-488	+	CGGCCUGGGGACAGCGG	17	973
  BCL11A-489	+	GGCCUGGGGACAGCGGU	17	974
  BCL11A-490	+	UCUCCUAGAGAAAUCCA	17	975
  BCL11A-491	+	CCUAGAGAAAUCCAUGG	17	976
  BCL11A-492	+	CUAGAGAAAUCCAUGGC	17	977
  BCL11A-493	+	GAGAAAUCCAUGGCGGG	17	978
  BCL11A-494	+	GGAGGCUCCAUAGCCAU	17	979
  BCL11A-495	+	CCGCAGCACCCUGUCAA	17	980
  BCL11A-496	+	ACCCUGUCAAAGGCACU	17	981
  BCL11A-497	+	CCCUGUCAAAGGCACUC	17	982
  BCL11A-498	+	CAAAGGCACUCGGGUGA	17	983
  BCL11A-499	+	AAAGGCACUCGGGUGAU	17	984
  BCL11A-500	+	GGCACUCGGGUGAUGGG	17	985
  BCL11A-501	+	UCGGGUGAUGGGUGGCC	17	986
  BCL11A-502	+	CGGGUGAUGGGUGGCCA	17	987
  BCL11A-503	+	CCAUCUCUUCCGCCCCC	17	988
  BCL11A-504	+	CCCCCAGGCGCUCUAUG	17	989
  BCL11A-505	+	CCAGGCGCUCUAUGCGG	17	990
  BCL11A-506	+	CAGGCGCUCUAUGCGGU	17	991
  BCL11A-507	+	AGGCGCUCUAUGCGGUG	17	992
  BCL11A-508	+	GGCGCUCUAUGCGGUGG	17	993
  BCL11A-509	+	GGGUCCAAGUGAUGUCU	17	994
  BCL11A-510	+	UCCAAGUGAUGUCUCGG	17	995
  BCL11A-511	+	AAGUGAUGUCUCGGUGG	17	996
  BCL11A-512	+	UCGGUGGUGGACUAAAC	17	997
  BCL11A-513	+	CGGUGGUGGACUAAACA	17	998
  BCL11A-514	+	GGUGGUGGACUAAACAG	17	999
  BCL11A-515	+	GUGGUGGACUAAACAGG	17	1000
  BCL11A-516	+	UGGUGGACUAAACAGGG	17	1001
  BCL11A-517	+	GGUGGACUAAACAGGGG	17	1002
  BCL11A-518	+	ACUAAACAGGGGGGGAG	17	1003
  BCL11A-519	+	CUAAACAGGGGGGGAGU	17	1004
  BCL11A-520	+	AACAGGGGGGGAGUGGG	17	1005
  BCL11A-521	+	GAAAGCGCCCUUCUGCC	17	1006
  BCL11A-522	+	GCGCCCUUCUGCCAGGC	17	1007
  BCL11A-523	+	UCUCUCGAUACUGAUCC	17	1008
  BCL11A-524	+	AUCCUGGUAUUCUUAGC	17	1009
  BCL11A-525	+	UAUUCUUAGCAGGUUAA	17	1010
  BCL11A-526	+	AUUCUUAGCAGGUUAAA	17	1011
  BCL11A-527	+	UUCUUAGCAGGUUAAAG	17	1012
  BCL11A-528	+	CUGCAAUAUGAAUCCCA	17	1013
  BCL11A-529	+	AUAUGAAUCCCAUGGAG	17	1014
  BCL11A-530	+	UGAAUCCCAUGGAGAGG	17	1015
  BCL11A-531	+	UCCCAUGGAGAGGUGGC	17	1016
  BCL11A-532	+	CCCAUGGAGAGGUGGCU	17	1017
  BCL11A-533	+	UGGAGAGGUGGCUGGGA	17	1018
  BCL11A-534	+	UCUGCACCUAGUCCUGA	17	1019
  BCL11A-535	+	CUGCACCUAGUCCUGAA	17	1020
  BCL11A-536	+	GAAGGGAUACCAACCCG	17	1021
  BCL11A-537	+	AAGGGAUACCAACCCGC	17	1022
  BCL11A-538	+	AGGGAUACCAACCCGCG	17	1023
  BCL11A-539	+	UACCAACCCGCGGGGUC	17	1024
  BCL11A-540	+	ACCAACCCGCGGGGUCA	17	1025
  BCL11A-541	+	CCAACCCGCGGGGUCAG	17	1026
  BCL11A-542	+	CAAGAGAAACCAUGCAC	17	1027
  BCL11A-543	+	AACCAUGCACUGGUGAA	17	1028
  BCL11A-544	+	UGUACAUGUGUAGCUGC	17	1029
  BCL11A-545	+	GUACAUGUGUAGCUGCU	17	1030
  BCL11A-546	-	AGAGGAGGAGGAGGAGCUGA	20	1031
  BCL11A-547	-	AGGAGCUGACGGAGAGCGAG	20	1032
  BCL11A-548	-	GGAGCUGACGGAGAGCGAGA	20	1033
  BCL11A-549	-	GCUGACGGAGAGCGAGAGGG	20	1034
  BCL11A-550	-	GAGAGCGAGAGGGUGGACUA	20	1035
  BCL11A-551	-	GAGAGGGUGGACUACGGCUU	20	1036
  BCL11A-552	-	AGAGGGUGGACUACGGCUUC	20	1037
  BCL11A-553	-	CUACGGCUUCGGGCUGAGCC	20	1038
  BCL11A-554	-	CGGCUUCGGGCUGAGCCUGG	20	1039
  BCL11A-555	-	CUUCGGGCUGAGCCUGGAGG	20	1040
  BCL11A-556	-	GCCACCACGAGAACAGCUCG	20	1041
  BCL11A-557	-	CCACCACGAGAACAGCUCGC	20	1042
  BCL11A-558	-	CACCACGAGAACAGCUCGCG	20	1043
  BCL11A-559	-	CGAGAACAGCUCGCGGGGCG	20	1044
  BCL11A-560	-	CAGCUCGCGGGGCGCGGUCG	20	1045
  BCL11A-561	-	AGCUCGCGGGGCGCGGUCGU	20	1046
  BCL11A-562	-	GCGGGGCGCGGUCGUGGGCG	20	1047
  BCL11A-563	-	CGGGGCGCGGUCGUGGGCGU	20	1048
  BCL11A-564	-	CGCCCUGCCCGACGUCAUGC	20	1049
  BCL11A-565	-	GCCCUGCCCGACGUCAUGCA	20	1050
  BCL11A-566	-	GCCCGACGUCAUGCAGGGCA	20	1051
  BCL11A-567	-	CUCCAUGCAGCACUUCAGCG	20	1052
  BCL11A-568	-	CUUCAGCGAGGCCUUCCACC	20	1053
  BCL11A-569	-	CGAGGCCUUCCACCAGGUCC	20	1054
  BCL11A-570	-	GAGGCCUUCCACCAGGUCCU	20	1055
  BCL11A-571	-	CUGGGCGAGAAGCAUAAGCG	20	1056
  BCL11A-572	-	GAAGCAUAAGCGCGGCCACC	20	1057
  BCL11A-573	-	UAAGCGCGGCCACCUGGCCG	20	1058
  BCL11A-574	-	CGGCCACCUGGCCGAGGCCG	20	1059
  BCL11A-575	-	GGCCACCUGGCCGAGGCCGA	20	1060
  BCL11A-576	-	UGGCCGAGGCCGAGGGCCAC	20	1061
  BCL11A-577	-	GGCCGAGGCCGAGGGCCACA	20	1062
  BCL11A-578	-	GGACACUUGCGACGAAGACU	20	1063
  BCL11A-579	-	CACUUGCGACGAAGACUCGG	20	1064
  BCL11A-580	-	UGCGACGAAGACUCGGUGGC	20	1065
  BCL11A-581	-	AGACUCGGUGGCCGGCGAGU	20	1066
  BCL11A-582	-	GAGUCGGACCGCAUAGACGA	20	1067
  BCL11A-583	-	AUAGACGAUGGCACUGUUAA	20	1068
  BCL11A-584	-	GAUGGCACUGUUAAUGGCCG	20	1069
  BCL11A-585	-	UAAUGGCCGCGGCUGCUCCC	20	1070
  BCL11A-586	-	AAUGGCCGCGGCUGCUCCCC	20	1071
  BCL11A-587	-	CGGCUGCUCCCCGGGCGAGU	20	1072
  BCL11A-588	-	CUCCCCGGGCGAGUCGGCCU	20	1073
  BCL11A-589	-	UCCCCGGGCGAGUCGGCCUC	20	1074
  BCL11A-590	-	CCCCGGGCGAGUCGGCCUCG	20	1075
  BCL11A-591	-	CCCGGGCGAGUCGGCCUCGG	20	1076
  BCL11A-592	-	CCGGGCGAGUCGGCCUCGGG	20	1077
  BCL11A-593	-	CCUGUCCAAAAAGCUGCUGC	20	1078
  BCL11A-594	-	CUGUCCAAAAAGCUGCUGCU	20	1079
  BCL11A-595	-	UAAGCGCAUCAAGCUCGAGA	20	1080
  BCL11A-596	-	GAAGGAGUUCGACCUGCCCC	20	1081
  BCL11A-597	-	CCCGGCCGCGAUGCCCAACA	20	1082
  BCL11A-598	-	CGGAGAACGUGUACUCGCAG	20	1083
  BCL11A-599	-	GUGUACUCGCAGUGGCUCGC	20	1084
  BCL11A-600	-	GCAGUGGCUCGCCGGCUACG	20	1085
  BCL11A-601	-	UCGCCGGCUACGCGGCCUCC	20	1086
  BCL11A-602	-	AAAGAUCCCUUCCUUAGCUU	20	1087
  BCL11A-603	-	AUCGCCUUUUGCCUCCUCGU	20	1088
  BCL11A-604	-	CUCCUCGUCGGAGCACUCCU	20	1089
  BCL11A-605	-	UCGGAGCACUCCUCGGAGAA	20	1090
  BCL11A-606	-	CGGAGCACUCCUCGGAGAAC	20	1091
  BCL11A-607	-	UUGCGCUUCUCCACACCGCC	20	1092
  BCL11A-608	-	UGCGCUUCUCCACACCGCCC	20	1093
  BCL11A-609	-	GCGCUUCUCCACACCGCCCG	20	1094
  BCL11A-610	-	CUCCACACCGCCCGGGGAGC	20	1095
  BCL11A-611	-	ACACCGCCCGGGGAGCUGGA	20	1096
  BCL11A-612	-	CCGCCCGGGGAGCUGGACGG	20	1097
  BCL11A-613	-	CGCCCGGGGAGCUGGACGGA	20	1098
  BCL11A-614	-	GGAGCUGGACGGAGGGAUCU	20	1099
  BCL11A-615	-	GAGCUGGACGGAGGGAUCUC	20	1100
  BCL11A-616	-	AGCUGGACGGAGGGAUCUCG	20	1101
  BCL11A-617	-	GGAGGGAUCUCGGGGCGCAG	20	1102
  BCL11A-618	-	GAUCUCGGGGCGCAGCGGCA	20	1103
  BCL11A-619	-	AUCUCGGGGCGCAGCGGCAC	20	1104
  BCL11A-620	-	GGGCGCAGCGGCACGGGAAG	20	1105
  BCL11A-621	-	CGCAGCGGCACGGGAAGUGG	20	1106
  BCL11A-622	-	GCAGCGGCACGGGAAGUGGA	20	1107
  BCL11A-623	-	GGGAGCACGCCCCAUAUUAG	20	1108
  BCL11A-624	-	CACGCCCCAUAUUAGUGGUC	20	1109
  BCL11A-625	-	ACGCCCCAUAUUAGUGGUCC	20	1110
  BCL11A-626	-	CCAUAUUAGUGGUCCGGGCC	20	1111
  BCL11A-627	-	CAUAUUAGUGGUCCGGGCCC	20	1112
  BCL11A-628	-	UUAGUGGUCCGGGCCCGGGC	20	1113
  BCL11A-629	-	GGGCAGGCCCAGCUCAAAAG	20	1114
  BCL11A-630	-	GGCAGGCCCAGCUCAAAAGA	20	1115
  BCL11A-631	+	GCGUCUGCCCUCUUUUGAGC	20	1116
  BCL11A-632	+	CGUCUGCCCUCUUUUGAGCU	20	1117
  BCL11A-633	+	UCUUUUGAGCUGGGCCUGCC	20	1118
  BCL11A-634	+	CUUUUGAGCUGGGCCUGCCC	20	1119
  BCL11A-635	+	GAGCUGGGCCUGCCCGGGCC	20	1120
  BCL11A-636	+	CCGGGCCCGGACCACUAAUA	20	1121
  BCL11A-637	+	CGGGCCCGGACCACUAAUAU	20	1122
  BCL11A-638	+	GGGCCCGGACCACUAAUAUG	20	1123
  BCL11A-639	+	GAUCCCUCCGUCCAGCUCCC	20	1124
  BCL11A-640	+	AUCCCUCCGUCCAGCUCCCC	20	1125
  BCL11A-641	+	CCUCCGUCCAGCUCCCCGGG	20	1126
  BCL11A-642	+	GUCCAGCUCCCCGGGCGGUG	20	1127
  BCL11A-643	+	GCGCAAACUCCCGUUCUCCG	20	1128
  BCL11A-644	+	CUCCGAGGAGUGCUCCGACG	20	1129
  BCL11A-645	+	CGAGGAGUGCUCCGACGAGG	20	1130
  BCL11A-646	+	UGCUCCGACGAGGAGGCAAA	20	1131
  BCL11A-647	+	GGAGGCAAAAGGCGAUUGUC	20	1132
  BCL11A-648	+	GUCUGGAGUCUCCGAAGCUA	20	1133
  BCL11A-649	+	GGAGUCUCCGAAGCUAAGGA	20	1134
  BCL11A-650	+	GAGUCUCCGAAGCUAAGGAA	20	1135
  BCL11A-651	+	GAAGGGAUCUUUGAGCUGCC	20	1136
  BCL11A-652	+	GGGAUCUUUGAGCUGCCUGG	20	1137
  BCL11A-653	+	CUGCCUGGAGGCCGCGUAGC	20	1138
  BCL11A-654	+	CGAGUACACGUUCUCCGUGU	20	1139
  BCL11A-655	+	GAGUACACGUUCUCCGUGUU	20	1140
  BCL11A-656	+	GUUCUCCGUGUUGGGCAUCG	20	1141
  BCL11A-657	+	UCCGUGUUGGGCAUCGCGGC	20	1142
  BCL11A-658	+	CCGUGUUGGGCAUCGCGGCC	20	1143
  BCL11A-659	+	CGUGUUGGGCAUCGCGGCCG	20	1144
  BCL11A-660	+	GUGUUGGGCAUCGCGGCCGG	20	1145
  BCL11A-661	+	UGGGCAUCGCGGCCGGGGGC	20	1146
  BCL11A-662	+	GAGCUUGAUGCGCUUAGAGA	20	1147
  BCL11A-663	+	AGCUUGAUGCGCUUAGAGAA	20	1148
  BCL11A-664	+	GCUUGAUGCGCUUAGAGAAG	20	1149
  BCL11A-665	+	AGAGAAGGGGCUCAGCGAGC	20	1150
  BCL11A-666	+	GAGAAGGGGCUCAGCGAGCU	20	1151
  BCL11A-667	+	AGAAGGGGCUCAGCGAGCUG	20	1152
  BCL11A-668	+	GCUGCCCAGCAGCAGCUUUU	20	1153
  BCL11A-669	+	CCAGCAGCAGCUUUUUGGAC	20	1154
  BCL11A-670	+	CUUUUUGGACAGGCCCCCCG	20	1155
  BCL11A-671	+	CCCCCCGAGGCCGACUCGCC	20	1156
  BCL11A-672	+	CCCCCGAGGCCGACUCGCCC	20	1157
  BCL11A-673	+	CCCCGAGGCCGACUCGCCCG	20	1158
  BCL11A-674	+	ACUCGCCCGGGGAGCAGCCG	20	1159
  BCL11A-675	+	UAACAGUGCCAUCGUCUAUG	20	1160
  BCL11A-676	+	GUCUAUGCGGUCCGACUCGC	20	1161
  BCL11A-677	+	CUUCGUCGCAAGUGUCCCUG	20	1162
  BCL11A-678	+	GCAAGUGUCCCUGUGGCCCU	20	1163
  BCL11A-679	+	GUCCCUGUGGCCCUCGGCCU	20	1164
  BCL11A-680	+	UGUGGCCCUCGGCCUCGGCC	20	1165
  BCL11A-681	+	GGCCCUCGGCCUCGGCCAGG	20	1166
  BCL11A-682	+	CGCGCUUAUGCUUCUCGCCC	20	1167
  BCL11A-683	+	UAUGCUUCUCGCCCAGGACC	20	1168
  BCL11A-684	+	GCUUCUCGCCCAGGACCUGG	20	1169
  BCL11A-685	+	CUCGCCCAGGACCUGGUGGA	20	1170
  BCL11A-686	+	GGCCUCGCUGAAGUGCUGCA	20	1171
  BCL11A-687	+	CACCAUGCCCUGCAUGACGU	20	1172
  BCL11A-688	+	ACCAUGCCCUGCAUGACGUC	20	1173
  BCL11A-689	+	UGCCCUGCAUGACGUCGGGC	20	1174
  BCL11A-690	+	GCCCUGCAUGACGUCGGGCA	20	1175
  BCL11A-691	+	GCAUGACGUCGGGCAGGGCG	20	1176
  BCL11A-692	+	CGCCCCGCGAGCUGUUCUCG	20	1177
  BCL11A-693	+	CCCGCGAGCUGUUCUCGUGG	20	1178
  BCL11A-694	+	CGUGGUGGCGCGCCGCCUCC	20	1179
  BCL11A-695	-	GGAGGAAGAGGAGGAGG	17	1180
  BCL11A-696	-	GGAGGAGGAGGAGCUGA	17	1181
  BCL11A-697	-	AGCUGACGGAGAGCGAG	17	1182
  BCL11A-698	-	GCUGACGGAGAGCGAGA	17	1183
  BCL11A-699	-	GACGGAGAGCGAGAGGG	17	1184
  BCL11A-700	-	AGCGAGAGGGUGGACUA	17	1185
  BCL11A-701	-	AGGGUGGACUACGGCUU	17	1186
  BCL11A-702	-	GGGUGGACUACGGCUUC	17	1187
  BCL11A-703	-	CGGCUUCGGGCUGAGCC	17	1188
  BCL11A-704	-	CUUCGGGCUGAGCCUGG	17	1189
  BCL11A-705	-	CGGGCUGAGCCUGGAGG	17	1190
  BCL11A-706	-	ACCACGAGAACAGCUCG	17	1191
  BCL11A-707	-	CCACGAGAACAGCUCGC	17	1192
  BCL11A-708	-	CACGAGAACAGCUCGCG	17	1193
  BCL11A-709	-	GAACAGCUCGCGGGGCG	17	1194
  BCL11A-710	-	CUCGCGGGGCGCGGUCG	17	1195
  BCL11A-711	-	UCGCGGGGCGCGGUCGU	17	1196
  BCL11A-712	-	GGGCGCGGUCGUGGGCG	17	1197
  BCL11A-713	-	GGCGCGGUCGUGGGCGU	17	1198
  BCL11A-714	-	CCUGCCCGACGUCAUGC	17	1199
  BCL11A-715	-	CUGCCCGACGUCAUGCA	17	1200
  BCL11A-716	-	CGACGUCAUGCAGGGCA	17	1201
  BCL11A-717	-	CAUGCAGCACUUCAGCG	17	1202
  BCL11A-718	-	CAGCGAGGCCUUCCACC	17	1203
  BCL11A-719	-	GGCCUUCCACCAGGUCC	17	1204
  BCL11A-720	-	GCCUUCCACCAGGUCCU	17	1205
  BCL11A-721	-	GGCGAGAAGCAUAAGCG	17	1206
  BCL11A-722	-	GCAUAAGCGCGGCCACC	17	1207
  BCL11A-723	-	GCGCGGCCACCUGGCCG	17	1208
  BCL11A-724	-	CCACCUGGCCGAGGCCG	17	1209
  BCL11A-725	-	CACCUGGCCGAGGCCGA	17	1210
  BCL11A-726	-	CCGAGGCCGAGGGCCAC	17	1211
  BCL11A-727	-	CGAGGCCGAGGGCCACA	17	1212
  BCL11A-728	-	CACUUGCGACGAAGACU	17	1213
  BCL11A-729	-	UUGCGACGAAGACUCGG	17	1214
  BCL11A-730	-	GACGAAGACUCGGUGGC	17	1215
  BCL11A-731	-	CUCGGUGGCCGGCGAGU	17	1216
  BCL11A-732	-	UCGGACCGCAUAGACGA	17	1217
  BCL11A-733	-	GACGAUGGCACUGUUAA	17	1218
  BCL11A-734	-	GGCACUGUUAAUGGCCG	17	1219
  BCL11A-735	-	UGGCCGCGGCUGCUCCC	17	1220
  BCL11A-736	-	GGCCGCGGCUGCUCCCC	17	1221
  BCL11A-737	-	CUGCUCCCCGGGCGAGU	17	1222
  BCL11A-738	-	CCCGGGCGAGUCGGCCU	17	1223
  BCL11A-739	-	CCGGGCGAGUCGGCCUC	17	1224
  BCL11A-740	-	CGGGCGAGUCGGCCUCG	17	1225
  BCL11A-741	-	GGGCGAGUCGGCCUCGG	17	1226
  BCL11A-742	-	GGCGAGUCGGCCUCGGG	17	1227
  BCL11A-743	-	GUCCAAAAAGCUGCUGC	17	1228
  BCL11A-744	-	UCCAAAAAGCUGCUGCU	17	1229
  BCL11A-745	-	GCGCAUCAAGCUCGAGA	17	1230
  BCL11A-746	-	GGAGUUCGACCUGCCCC	17	1231
  BCL11A-747	-	GGCCGCGAUGCCCAACA	17	1232
  BCL11A-748	-	AGAACGUGUACUCGCAG	17	1233
  BCL11A-749	-	UACUCGCAGUGGCUCGC	17	1234
  BCL11A-750	-	GUGGCUCGCCGGCUACG	17	1235
  BCL11A-751	-	CCGGCUACGCGGCCUCC	17	1236
  BCL11A-752	-	GAUCCCUUCCUUAGCUU	17	1237
  BCL11A-753	-	GCCUUUUGCCUCCUCGU	17	1238
  BCL11A-754	-	CUCGUCGGAGCACUCCU	17	1239
  BCL11A-755	-	GAGCACUCCUCGGAGAA	17	1240
  BCL11A-756	-	AGCACUCCUCGGAGAAC	17	1241
  BCL11A-757	-	CGCUUCUCCACACCGCC	17	1242
  BCL11A-758	-	GCUUCUCCACACCGCCC	17	1243
  BCL11A-759	-	CUUCUCCACACCGCCCG	17	1244
  BCL11A-760	-	CACACCGCCCGGGGAGC	17	1245
  BCL11A-761	-	CCGCCCGGGGAGCUGGA	17	1246
  BCL11A-762	-	CCCGGGGAGCUGGACGG	17	1247
  BCL11A-763	-	CCGGGGAGCUGGACGGA	17	1248
  BCL11A-764	-	GCUGGACGGAGGGAUCU	17	1249
  BCL11A-765	-	CUGGACGGAGGGAUCUC	17	1250
  BCL11A-766	-	UGGACGGAGGGAUCUCG	17	1251
  BCL11A-767	-	GGGAUCUCGGGGCGCAG	17	1252
  BCL11A-768	-	CUCGGGGCGCAGCGGCA	17	1253
  BCL11A-769	-	UCGGGGCGCAGCGGCAC	17	1254
  BCL11A-770	-	CGCAGCGGCACGGGAAG	17	1255
  BCL11A-771	-	AGCGGCACGGGAAGUGG	17	1256
  BCL11A-772	-	GCGGCACGGGAAGUGGA	17	1257
  BCL11A-773	-	AGCACGCCCCAUAUUAG	17	1258
  BCL11A-774	-	GCCCCAUAUUAGUGGUC	17	1259
  BCL11A-775	-	CCCCAUAUUAGUGGUCC	17	1260
  BCL11A-776	-	UAUUAGUGGUCCGGGCC	17	1261
  BCL11A-777	-	AUUAGUGGUCCGGGCCC	17	1262
  BCL11A-778	-	GUGGUCCGGGCCCGGGC	17	1263
  BCL11A-779	-	CAGGCCCAGCUCAAAAG	17	1264
  BCL11A-780	-	AGGCCCAGCUCAAAAGA	17	1265
  BCL11A-781	+	UCUGCCCUCUUUUGAGC	17	1266
  BCL11A-782	+	CUGCCCUCUUUUGAGCU	17	1267
  BCL11A-783	+	UUUGAGCUGGGCCUGCC	17	1268
  BCL11A-784	+	UUGAGCUGGGCCUGCCC	17	1269
  BCL11A-785	+	CUGGGCCUGCCCGGGCC	17	1270
  BCL11A-786	+	GGCCCGGACCACUAAUA	17	1271
  BCL11A-787	+	GCCCGGACCACUAAUAU	17	1272
  BCL11A-788	+	CCCGGACCACUAAUAUG	17	1273
  BCL11A-789	+	CCCUCCGUCCAGCUCCC	17	1274
  BCL11A-790	+	CCUCCGUCCAGCUCCCC	17	1275
  BCL11A-791	+	CCGUCCAGCUCCCCGGG	17	1276
  BCL11A-792	+	CAGCUCCCCGGGCGGUG	17	1277
  BCL11A-793	+	CAAACUCCCGUUCUCCG	17	1278
  BCL11A-794	+	CGAGGAGUGCUCCGACG	17	1279
  BCL11A-795	+	GGAGUGCUCCGACGAGG	17	1280
  BCL11A-796	+	UCCGACGAGGAGGCAAA	17	1281
  BCL11A-797	+	GGCAAAAGGCGAUUGUC	17	1282
  BCL11A-798	+	UGGAGUCUCCGAAGCUA	17	1283
  BCL11A-799	+	GUCUCCGAAGCUAAGGA	17	1284
  BCL11A-800	+	UCUCCGAAGCUAAGGAA	17	1285
  BCL11A-801	+	GGGAUCUUUGAGCUGCC	17	1286
  BCL11A-802	+	AUCUUUGAGCUGCCUGG	17	1287
  BCL11A-803	+	CCUGGAGGCCGCGUAGC	17	1288
  BCL11A-804	+	GUACACGUUCUCCGUGU	17	1289
  BCL11A-805	+	UACACGUUCUCCGUGUU	17	1290
  BCL11A-806	+	CUCCGUGUUGGGCAUCG	17	1291
  BCL11A-807	+	GUGUUGGGCAUCGCGGC	17	1292
  BCL11A-808	+	UGUUGGGCAUCGCGGCC	17	1293
  BCL11A-809	+	GUUGGGCAUCGCGGCCG	17	1294
  BCL11A-810	+	UUGGGCAUCGCGGCCGG	17	1295
  BCL11A-811	+	GCAUCGCGGCCGGGGGC	17	1296
  BCL11A-812	+	CUUGAUGCGCUUAGAGA	17	1297
  BCL11A-813	+	UUGAUGCGCUUAGAGAA	17	1298
  BCL11A-814	+	UGAUGCGCUUAGAGAAG	17	1299
  BCL11A-815	+	GAAGGGGCUCAGCGAGC	17	1300
  BCL11A-816	+	AAGGGGCUCAGCGAGCU	17	1301
  BCL11A-817	+	AGGGGCUCAGCGAGCUG	17	1302
  BCL11A-818	+	GCCCAGCAGCAGCUUUU	17	1303
  BCL11A-819	+	GCAGCAGCUUUUUGGAC	17	1304
  BCL11A-820	+	UUUGGACAGGCCCCCCG	17	1305
  BCL11A-821	+	CCCGAGGCCGACUCGCC	17	1306
  BCL11A-822	+	CCGAGGCCGACUCGCCC	17	1307
  BCL11A-823	+	CGAGGCCGACUCGCCCG	17	1308
  BCL11A-824	+	CGCCCGGGGAGCAGCCG	17	1309
  BCL11A-825	+	CAGUGCCAUCGUCUAUG	17	1310
  BCL11A-826	+	UAUGCGGUCCGACUCGC	17	1311
  BCL11A-827	+	CGUCGCAAGUGUCCCUG	17	1312
  BCL11A-828	+	AGUGUCCCUGUGGCCCU	17	1313
  BCL11A-829	+	CCUGUGGCCCUCGGCCU	17	1314
  BCL11A-830	+	GGCCCUCGGCCUCGGCC	17	1315
  BCL11A-831	+	CCUCGGCCUCGGCCAGG	17	1316
  BCL11A-832	+	GCUUAUGCUUCUCGCCC	17	1317
  BCL11A-833	+	GCUUCUCGCCCAGGACC	17	1318
  BCL11A-834	+	UCUCGCCCAGGACCUGG	17	1319
  BCL11A-835	+	GCCCAGGACCUGGUGGA	17	1320
  BCL11A-836	+	CUCGCUGAAGUGCUGCA	17	1321
  BCL11A-837	+	CAUGCCCUGCAUGACGU	17	1322
  BCL11A-838	+	AUGCCCUGCAUGACGUC	17	1323
  BCL11A-839	+	CCUGCAUGACGUCGGGC	17	1324
  BCL11A-840	+	CUGCAUGACGUCGGGCA	17	1325
  BCL11A-841	+	UGACGUCGGGCAGGGCG	17	1326
  BCL11A-842	+	CCCGCGAGCUGUUCUCG	17	1327
  BCL11A-843	+	GCGAGCUGUUCUCGUGG	17	1328
  BCL11A-844	+	GGUGGCGCGCCGCCUCC	17	1329
  BCL11A-845	-	CCCAGAGAGCUCAAGAUGUG	20	1330
  BCL11A-846	-	UCAAGAUGUGUGGCAGUUUU	20	1331
  BCL11A-847	-	GAUGUGUGGCAGUUUUCGGA	20	1332
  BCL11A-848	+	GCCACACAUCUUGAGCUCUC	20	1333
  BCL11A-849	+	CCACACAUCUUGAGCUCUCU	20	1334
  BCL11A-850	+	UCUCUGGGUACUACGCCGAA	20	1335
  BCL11A-851	+	CUCUGGGUACUACGCCGAAU	20	1336
  BCL11A-852	+	UCUGGGUACUACGCCGAAUG	20	1337
  BCL11A-853	+	CUGGGUACUACGCCGAAUGG	20	1338
  BCL11A-854	-	CUUCACACACCCCCAUU	17	1339
  BCL11A-855	-	AGAGAGCUCAAGAUGUG	17	1340
  BCL11A-856	-	AGAUGUGUGGCAGUUUU	17	1341
  BCL11A-857	-	GUGUGGCAGUUUUCGGA	17	1342
  BCL11A-858	+	ACACAUCUUGAGCUCUC	17	1343
  BCL11A-859	+	CACAUCUUGAGCUCUCU	17	1344
  BCL11A-860	+	CUGGGUACUACGCCGAA	17	1345
  BCL11A-861	+	UGGGUACUACGCCGAAU	17	1346
  BCL11A-862	+	GGGUACUACGCCGAAUG	17	1347
  BCL11A-863	+	GGUACUACGCCGAAUGG	17	1348

• Table 2E provides exemplary targeting domains for knocking out the BCL11A 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 a S. aureus Cas9 molecule that gives double stranded cleavage. Any of the targeting domains in the table can be used with a S. aureus Cas9 single-stranded break nucleases (nickases). In an embodiment, dual targeting is used to create two nicks. 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 2E
  S. aureus gRNA targets for BCL11A knockout

  	DNA		Target Site	SEQ ID
  gRNA Name	Strand	Targeting Domain	Length	NO
  BCL11A-864	-	AAACCCCAGCACUUAAGCAA	20	1349
  BCL11A-865	-	AACCCCAGCACUUAAGCAAA	20	1350
  BCL11A-866	-	ACCCCAGCACUUAAGCAAAC	20	1351
  BCL11A-867	-	CCCCAGCACUUAAGCAA	17	1352
  BCL11A-868	-	CCCAGCACUUAAGCAAA	17	1353
  BCL11A-869	-	CCAGCACUUAAGCAAAC	17	1354
  BCL11A-870	+	UGGGGUUUGCCUUGCUUGCG	20	1355
  BCL11A-871	+	AUUCCCGUUUGCUUAAGUGC	20	1356
  BCL11A-872	+	AAUUCCCGUUUGCUUAAGUG	20	1357
  BCL11A-873	+	GGUUUGCCUUGCUUGCG	17	1358
  BCL11A-874	+	CCCGUUUGCUUAAGUGC	17	1359
  BCL11A-875	+	UCCCGUUUGCUUAAGUG	17	1360
  BCL11A-876	-	UGAAGCCAUUCUUACAGAUG	20	1361
  BCL11A-877	-	AUGAACCAGACCACGGCCCG	20	1362
  BCL11A-878	-	UGAACCAGACCACGGCCCGU	20	1363
  BCL11A-879	-	GAACCAGACCACGGCCCGUU	20	1364
  BCL11A-880	-	CCACGGCCCGUUGGGAGCUC	20	1365
  BCL11A-881	-	CGGCCCGUUGGGAGCUCCAG	20	1366
  BCL11A-882	-	GGCCCGUUGGGAGCUCCAGA	20	1367
  BCL11A-883	-	GCCCGUUGGGAGCUCCAGAA	20	1368
  BCL11A-884	-	GGAUCAUGACCUCCUCACCU	20	1369
  BCL11A-885	-	UCACCUGUGGGCAGUGCCAG	20	1370
  BCL11A-886	-	AGUGCCAGAUGAACUUCCCA	20	1371
  BCL11A-887	-	GUGCCAGAUGAACUUCCCAU	20	1372
  BCL11A-888	-	UGCCAGAUGAACUUCCCAUU	20	1373
  BCL11A-889	-	GCCAGAUGAACUUCCCAUUG	20	1374
  BCL11A-890	-	GGGGGACAUUCUUAUUUUUA	20	1375
  BCL11A-891	-	CUUAUUUUUAUCGAGCACAA	20	1376
  BCL11A-892	-	UUAUUUUUAUCGAGCACAAA	20	1377
  BCL11A-893	-	AUGCAAUGGCAGCCUCUGCU	20	1378
  BCL11A-894	-	GCCUCUGCUUAGAAAAAGCU	20	1379
  BCL11A-895	-	GCCACCUUCCCCUUCACCAA	20	1380
  BCL11A-896	-	CUUCCCCUUCACCAAUCGAG	20	1381
  BCL11A-897	-	UGAAAAAAGCAUCCAAUCCC	20	1382
  BCL11A-898	-	GAAAAAAGCAUCCAAUCCCG	20	1383
  BCL11A-899	-	GGUUGGCAUCCAGGUCACGC	20	1384
  BCL11A-900	-	UUGGCAUCCAGGUCACGCCA	20	1385
  BCL11A-901	-	GAUUGUUUAUCAACGUCAUC	20	1386
  BCL11A-902	-	UUGUUUAUCAACGUCAUCUA	20	1387
  BCL11A-903	-	UGUUUAUCAACGUCAUCUAG	20	1388
  BCL11A-904	-	CUAGAGGAAUUUGCCCCAAA	20	1389
  BCL11A-905	-	UAGAGGAAUUUGCCCCAAAC	20	1390
  BCL11A-906	-	AGCCAUUCUUACAGAUG	17	1391
  BCL11A-907	-	AACCAGACCACGGCCCG	17	1392
  BCL11A-908	-	ACCAGACCACGGCCCGU	17	1393
  BCL11A-909	-	CCAGACCACGGCCCGUU	17	1394
  BCL11A-910	-	CGGCCCGUUGGGAGCUC	17	1395
  BCL11A-911	-	CCCGUUGGGAGCUCCAG	17	1396
  BCL11A-912	-	CCGUUGGGAGCUCCAGA	17	1397
  BCL11A-913	-	CGUUGGGAGCUCCAGAA	17	1398
  BCL11A-914	-	UCAUGACCUCCUCACCU	17	1399
  BCL11A-915	-	CCUGUGGGCAGUGCCAG	17	1400
  BCL11A-916	-	GCCAGAUGAACUUCCCA	17	1401
  BCL11A-917	-	CCAGAUGAACUUCCCAU	17	1402
  BCL11A-918	-	CAGAUGAACUUCCCAUU	17	1403
  BCL11A-919	-	AGAUGAACUUCCCAUUG	17	1404
  BCL11A-920	-	GGACAUUCUUAUUUUUA	17	1405
  BCL11A-921	-	AUUUUUAUCGAGCACAA	17	1406
  BCL11A-922	-	UUUUUAUCGAGCACAAA	17	1407
  BCL11A-923	-	CAAUGGCAGCCUCUGCU	17	1408
  BCL11A-924	-	UCUGCUUAGAAAAAGCU	17	1409
  BCL11A-925	-	ACCUUCCCCUUCACCAA	17	1410
  BCL11A-926	-	CCCCUUCACCAAUCGAG	17	1411
  BCL11A-927	-	AAAAAGCAUCCAAUCCC	17	1412
  BCL11A-928	-	AAAAGCAUCCAAUCCCG	17	1413
  BCL11A-929	-	UGGCAUCCAGGUCACGC	17	1414
  BCL11A-930	-	GCAUCCAGGUCACGCCA	17	1415
  BCL11A-931	-	UGUUUAUCAACGUCAUC	17	1416
  BCL11A-932	-	UUUAUCAACGUCAUCUA	17	1417
  BCL11A-933	-	UUAUCAACGUCAUCUAG	17	1418
  BCL11A-934	-	GAGGAAUUUGCCCCAAA	17	1419
  BCL11A-935	-	AGGAAUUUGCCCCAAAC	17	1420
  BCL11A-936	+	UCAUCUGUAAGAAUGGCUUC	20	1421
  BCL11A-937	+	UGGUCUGGUUCAUCAUCUGU	20	1422
  BCL11A-938	+	AUCCCCUUCUGGAGCUCCCA	20	1423
  BCL11A-939	+	AGGAGGUCAUGAUCCCCUUC	20	1424
  BCL11A-940	+	GAGGAGGUCAUGAUCCCCUU	20	1425
  BCL11A-941	+	UCUGGCACUGCCCACAGGUG	20	1426
  BCL11A-942	+	AUCUGGCACUGCCCACAGGU	20	1427
  BCL11A-943	+	UCAUCUGGCACUGCCCACAG	20	1428
  BCL11A-944	+	AAAUAAGAAUGUCCCCCAAU	20	1429
  BCL11A-945	+	AAAAUAAGAAUGUCCCCCAA	20	1430
  BCL11A-946	+	AAAAAUAAGAAUGUCCCCCA	20	1431
  BCL11A-947	+	CGUUUGUGCUCGAUAAAAAU	20	1432
  BCL11A-948	+	UAUCCACAGCUUUUUCUAAG	20	1433
  BCL11A-949	+	UUUCAUCUCGAUUGGUGAAG	20	1434
  BCL11A-950	+	UUUUCAUCUCGAUUGGUGAA	20	1435
  BCL11A-951	+	UUUUUCAUCUCGAUUGGUGA	20	1436
  BCL11A-952	+	UUUUUUCAUCUCGAUUGGUG	20	1437
  BCL11A-953	+	UGCUUUUUUCAUCUCGAUUG	20	1438
  BCL11A-954	+	GGAUGCCAACCUCCACGGGA	20	1439
  BCL11A-955	+	GACCUGGAUGCCAACCUCCA	20	1440
  BCL11A-956	+	UGACCUGGAUGCCAACCUCC	20	1441
  BCL11A-957	+	UCGUCAUCCUCUGGCGUGAC	20	1442
  BCL11A-958	+	CUGCUAUGUGUUCCUGUUUG	20	1443
  BCL11A-959	+	CUGCUAUGUGUUCCUGUUUG	20	1444
  BCL11A-960	+	UCUGUAAGAAUGGCUUC	17	1445
  BCL11A-961	+	UCUGGUUCAUCAUCUGU	17	1446
  BCL11A-962	+	CCCUUCUGGAGCUCCCA	17	1447
  BCL11A-963	+	AGGUCAUGAUCCCCUUC	17	1448
  BCL11A-964	+	GAGGUCAUGAUCCCCUU	17	1449
  BCL11A-965	+	GGCACUGCCCACAGGUG	17	1450
  BCL11A-966	+	UGGCACUGCCCACAGGU	17	1451
  BCL11A-967	+	UCUGGCACUGCCCACAG	17	1452
  BCL11A-968	+	UAAGAAUGUCCCCCAAU	17	1453
  BCL11A-969	+	AUAAGAAUGUCCCCCAA	17	1454
  BCL11A-970	+	AAUAAGAAUGUCCCCCA	17	1455
  BCL11A-971	+	UUGUGCUCGAUAAAAAU	17	1456
  BCL11A-972	+	CCACAGCUUUUUCUAAG	17	1457
  BCL11A-973	+	CAUCUCGAUUGGUGAAG	17	1458
  BCL11A-974	+	UCAUCUCGAUUGGUGAA	17	1459
  BCL11A-975	+	UUCAUCUCGAUUGGUGA	17	1460
  BCL11A-976	+	UUUCAUCUCGAUUGGUG	17	1461
  BCL11A-977	+	UUUUUUCAUCUCGAUUG	17	1462
  BCL11A-978	+	UGCCAACCUCCACGGGA	17	1463
  BCL11A-979	+	CUGGAUGCCAACCUCCA	17	1464
  BCL11A-980	+	CCUGGAUGCCAACCUCC	17	1465
  BCL11A-981	+	UCAUCCUCUGGCGUGAC	17	1466
  BCL11A-982	+	UGCUAUGUGUUCCUGUU	17	1467
  BCL11A-983	+	CUGCUAUGUGUUCCUGU	17	1468
  BCL11A-984	-	CUCCUCCCCUCGUUCUGCAC	20	1469
  BCL11A-985	-	UCCUCCCCUCGUUCUGCACA	20	1470
  BCL11A-986	-	UGGAGCUCUAAUCCCCACGC	20	1471
  BCL11A-987	-	GGAGCUCUAAUCCCCACGCC	20	1472
  BCL11A-988	-	CUCUAAUCCCCACGCCUGGG	20	1473
  BCL11A-989	-	CCCCACGCCUGGGAUGAGUG	20	1474
  BCL11A-990	-	UGAGUGCAGAAUAUGCCCCG	20	1475
  BCL11A-991	-	CUCCCCUCGUUCUGCAC	17	1476
  BCL11A-992	-	UCCCCUCGUUCUGCACA	17	1477
  BCL11A-993	-	AGCUCUAAUCCCCACGC	17	1478
  BCL11A-994	-	GCUCUAAUCCCCACGCC	17	1479
  BCL11A-995	-	UAAUCCCCACGCCUGGG	17	1480
  BCL11A-996	-	CACGCCUGGGAUGAGUG	17	1481
  BCL11A-997	-	GUGCAGAAUAUGCCCCG	17	1482
  BCL11A-998	+	GAGGAGAGGCCCCUCCAGUG	20	1483
  BCL11A-999	+	CAUGUGCAGAACGAGGGGAG	20	1484
  BCL11A-1000	+	UCCAUGUGCAGAACGAGGGG	20	1485
  BCL11A-1001	+	CUCCAUGUGCAGAACGAGGG	20	1486
  BCL11A-1002	+	AGCUCCAUGUGCAGAACGAG	20	1487
  BCL11A-1003	+	GAGCUCCAUGUGCAGAACGA	20	1488
  BCL11A-1004	+	AGAGCUCCAUGUGCAGAACG	20	1489
  BCL11A-1005	+	UAGAGCUCCAUGUGCAGAAC	20	1490
  BCL11A-1006	+	AUUAGAGCUCCAUGUGCAGA	20	1491
  BCL11A-1007	+	GGGGAUUAGAGCUCCAUGUG	20	1492
  BCL11A-1008	+	CUCAUCCCAGGCGUGGGGAU	20	1493
  BCL11A-1009	+	UCUGCACUCAUCCCAGGCGU	20	1494
  BCL11A-1010	+	UUCUGCACUCAUCCCAGGCG	20	1495
  BCL11A-1011	+	AUUCUGCACUCAUCCCAGGC	20	1496
  BCL11A-1012	+	GAGAGGCCCCUCCAGUG	17	1497
  BCL11A-1013	+	GUGCAGAACGAGGGGAG	17	1498
  BCL11A-1014	+	AUGUGCAGAACGAGGGG	17	1499
  BCL11A-1015	+	CAUGUGCAGAACGAGGG	17	1500
  BCL11A-1016	+	UCCAUGUGCAGAACGAG	17	1501
  BCL11A-1017	+	CUCCAUGUGCAGAACGA	17	1502
  BCL11A-1018	+	GCUCCAUGUGCAGAACG	17	1503
  BCL11A-1019	+	AGCUCCAUGUGCAGAAC	17	1504
  BCL11A-1020	+	AGAGCUCCAUGUGCAGA	17	1505
  BCL11A-1021	+	GAUUAGAGCUCCAUGUG	17	1506
  BCL11A-1022	+	AUCCCAGGCGUGGGGAU	17	1507
  BCL11A-1023	+	GCACUCAUCCCAGGCGU	17	1508
  BCL11A-1024	+	UGCACUCAUCCCAGGCG	17	1509
  BCL11A-1025	+	CUGCACUCAUCCCAGGC	17	1510
  BCL11A-1026	-	GGUUUCUCUUGCAACACGCA	20	1511
  BCL11A-1027	-	GCAACACGCACAGAACACUC	20	1512
  BCL11A-1028	-	GCACAGAACACUCAUGGAUU	20	1513
  BCL11A-1029	-	UCAUGGAUUAAGAAUCUACU	20	1514
  BCL11A-1030	-	AUUAAGAAUCUACUUAGAAA	20	1515
  BCL11A-1031	-	AAUCUACUUAGAAAGCGAAC	20	1516
  BCL11A-1032	-	AUCUACUUAGAAAGCGAACA	20	1517
  BCL11A-1033	-	CACGGAAGUCCCCUGACCCC	20	1518
  BCL11A-1034	-	CCCGCGGGUUGGUAUCCCUU	20	1519
  BCL11A-1035	-	UAUCCCUUCAGGACUAGGUG	20	1520
  BCL11A-1036	-	UCCUUCCCAGCCACCUCUCC	20	1521
  BCL11A-1037	-	CCUUCCCAGCCACCUCUCCA	20	1522
  BCL11A-1038	-	AAUAACCCCUUUAACCUGCU	20	1523
  BCL11A-1039	-	CUUUAACCUGCUAAGAAUAC	20	1524
  BCL11A-1040	-	UAAGAAUACCAGGAUCAGUA	20	1525
  BCL11A-1041	-	AGAAUACCAGGAUCAGUAUC	20	1526
  BCL11A-1042	-	AAUACCAGGAUCAGUAUCGA	20	1527
  BCL11A-1043	-	GAGAGAGGCUUCCGGCCUGG	20	1528
  BCL11A-1044	-	AGAGGCUUCCGGCCUGGCAG	20	1529
  BCL11A-1045	-	CCCCCCUGUUUAGUCCACCA	20	1530
  BCL11A-1046	-	GUCCACCACCGAGACAUCAC	20	1531
  BCL11A-1047	-	UCACUUGGACCCCCACCGCA	20	1532
  BCL11A-1048	-	ACCCCCACCGCAUAGAGCGC	20	1533
  BCL11A-1049	-	CCCCCACCGCAUAGAGCGCC	20	1534
  BCL11A-1050	-	CCCCACCGCAUAGAGCGCCU	20	1535
  BCL11A-1051	-	ACCGCAUAGAGCGCCUGGGG	20	1536
  BCL11A-1052	-	CCGCAUAGAGCGCCUGGGGG	20	1537
  BCL11A-1053	-	CAUAGAGCGCCUGGGGGCGG	20	1538
  BCL11A-1054	-	UGGCCCUGGCCACCCAUCAC	20	1539
  BCL11A-1055	-	CAUCACCCGAGUGCCUUUGA	20	1540
  BCL11A-1056	-	CCUUUGACAGGGUGCUGCGG	20	1541
  BCL11A-1057	-	UGCGGUUGAAUCCAAUGGCU	20	1542
  BCL11A-1058	-	GCGGUUGAAUCCAAUGGCUA	20	1543
  BCL11A-1059	-	UGGCUAUGGAGCCUCCCGCC	20	1544
  BCL11A-1060	-	CCUCCCGCCAUGGAUUUCUC	20	1545
  BCL11A-1061	-	CUCCCGCCAUGGAUUUCUCU	20	1546
  BCL11A-1062	-	AUGGAUUUCUCUAGGAGACU	20	1547
  BCL11A-1063	-	GGAUUUCUCUAGGAGACUUA	20	1548
  BCL11A-1064	-	UAGGAGACUUAGAGAGCUGG	20	1549
  BCL11A-1065	-	AGGAGACUUAGAGAGCUGGC	20	1550
  BCL11A-1066	-	GGAGACUUAGAGAGCUGGCA	20	1551
  BCL11A-1067	-	CCCGGUCAAGUCCAAGUCAU	20	1552
  BCL11A-1068	-	GCGGCAAGACGUUCAAAUUU	20	1553
  BCL11A-1069	-	UGGUGCACCGGCGCAGCCAC	20	1554
  BCL11A-1070	-	GCACCGGCGCAGCCACACGG	20	1555
  BCL11A-1071	-	ACCGGCGCAGCCACACGGGC	20	1556
  BCL11A-1072	-	CGUGCACCCAGGCCAGCAAG	20	1557
  BCL11A-1073	-	CCAGCAAGCUGAAGCGCCAC	20	1558
  BCL11A-1074	-	GUCUCUCCACCGCCAGCUCC	20	1559
  BCL11A-1075	-	UCUCUCCACCGCCAGCUCCC	20	1560
  BCL11A-1076	-	AACCCGGCACCAGCGACUUG	20	1561
  BCL11A-1077	-	AGUCCGUGGUGGCCAAGUUC	20	1562
  BCL11A-1078	-	CGUGGUGGCCAAGUUCAAGA	20	1563
  BCL11A-1079	-	UGGUGGCCAAGUUCAAGAGC	20	1564
  BCL11A-1080	-	AGAACGACCCCAACCUGAUC	20	1565
  BCL11A-1081	-	GAACGACCCCAACCUGAUCC	20	1566
  BCL11A-1082	-	ACGACCCCAACCUGAUCCCG	20	1567
  BCL11A-1083	-	CCCCAACCUGAUCCCGGAGA	20	1568
  BCL11A-1084	-	CCCAACCUGAUCCCGGAGAA	20	1569
  BCL11A-1085	-	CCAACCUGAUCCCGGAGAAC	20	1570
  BCL11A-1086	-	CCUGAUCCCGGAGAACGGGG	20	1571
  BCL11A-1087	-	UGAUCCCGGAGAACGGGGAC	20	1572
  BCL11A-1088	-	GAUCCCGGAGAACGGGGACG	20	1573
  BCL11A-1089	-	UCCCGGAGAACGGGGACGAG	20	1574
  BCL11A-1090	-	CCCGGAGAACGGGGACGAGG	20	1575
  BCL11A-1091	-	GGAGAACGGGGACGAGGAGG	20	1576
  BCL11A-1092	-	AGAACGGGGACGAGGAGGAA	20	1577
  BCL11A-1093	-	GAACGGGGACGAGGAGGAAG	20	1578
  BCL11A-1094	-	ACGGGGACGAGGAGGAAGAG	20	1579
  BCL11A-1095	-	CGAGGAGGAAGAGGAGGACG	20	1580
  BCL11A-1096	-	AGGAGGAAGAGGAGGACGAC	20	1581
  BCL11A-1097	-	GGAGGAAGAGGAGGACGACG	20	1582
  BCL11A-1098	-	GGAAGAGGAGGACGACGAGG	20	1583
  BCL11A-1099	-	AAGAGGAGGACGACGAGGAA	20	1584
  BCL11A-1100	-	AGAGGAGGACGACGAGGAAG	20	1585
  BCL11A-1101	-	GGAGGACGACGAGGAAGAGG	20	1586
  BCL11A-1102	-	GGACGACGAGGAAGAGGAAG	20	1587
  BCL11A-1103	-	ACGACGAGGAAGAGGAAGAA	20	1588
  BCL11A-1104	-	CGACGAGGAAGAGGAAGAAG	20	1589
  BCL11A-1105	-	ACGAGGAAGAGGAAGAAGAG	20	1590
  BCL11A-1106	-	CGAGGAAGAGGAAGAAGAGG	20	1591
  BCL11A-1107	-	GGAAGAGGAAGAAGAGGAGG	20	1592
  BCL11A-1108	-	AAGAGGAAGAAGAGGAGGAA	20	1593
  BCL11A-1109	-	AGAGGAAGAAGAGGAGGAAG	20	1594
  BCL11A-1110	-	AGGAAGAAGAGGAGGAAGAG	20	1595
  BCL11A-1111	-	GGAAGAAGAGGAGGAAGAGG	20	1596
  BCL11A-1112	-	AAGAAGAGGAGGAAGAGGAG	20	1597
  BCL11A-1113	-	AGAAGAGGAGGAAGAGGAGG	20	1598
  BCL11A-1114	-	AAGAGGAGGAAGAGGAGGAG	20	1599
  BCL11A-1115	-	AGAGGAGGAAGAGGAGGAGG	20	1600
  BCL11A-1116	-	AAGAGGAGGAGGAGGAGCUG	20	1601
  BCL11A-1117	-	AGAGGAGGAGGAGGAGCUGA	20	1602
  BCL11A-1118	-	AGGAGGAGGAGGAGCUGACG	20	1603
  BCL11A-1119	-	GGAGGAGGAGCUGACGGAGA	20	1604
  BCL11A-1120	-	AGGAGGAGCUGACGGAGAGC	20	1605
  BCL11A-1121	-	GAGGAGCUGACGGAGAGCGA	20	1606
  BCL11A-1122	-	AGCUGACGGAGAGCGAGAGG	20	1607
  BCL11A-1123	-	CGAGAGGGUGGACUACGGCU	20	1608
  BCL11A-1124	-	GGGUGGACUACGGCUUCGGG	20	1609
  BCL11A-1125	-	ACUACGGCUUCGGGCUGAGC	20	1610
  BCL11A-1126	-	CUACGGCUUCGGGCUGAGCC	20	1611
  BCL11A-1127	-	CCUGGAGGCGGCGCGCCACC	20	1612
  BCL11A-1128	-	UGGAGGCGGCGCGCCACCAC	20	1613
  BCL11A-1129	-	CGCCACCACGAGAACAGCUC	20	1614
  BCL11A-1130	-	GCCACCACGAGAACAGCUCG	20	1615
  BCL11A-1131	-	ACAGCUCGCGGGGCGCGGUC	20	1616
  BCL11A-1132	-	CGCGGGGCGCGGUCGUGGGC	20	1617
  BCL11A-1133	-	CGCGGUCGUGGGCGUGGGCG	20	1618
  BCL11A-1134	-	CGGUCGUGGGCGUGGGCGAC	20	1619
  BCL11A-1135	-	GCGCCCUGCCCGACGUCAUG	20	1620
  BCL11A-1136	-	CAGCUCCAUGCAGCACUUCA	20	1621
  BCL11A-1137	-	GCGAGGCCUUCCACCAGGUC	20	1622
  BCL11A-1138	-	GGCCUUCCACCAGGUCCUGG	20	1623
  BCL11A-1139	-	CCUUCCACCAGGUCCUGGGC	20	1624
  BCL11A-1140	-	GCAUAAGCGCGGCCACCUGG	20	1625
  BCL11A-1141	-	GCGCGGCCACCUGGCCGAGG	20	1626
  BCL11A-1142	-	GCGGCCACCUGGCCGAGGCC	20	1627
  BCL11A-1143	-	CUGGCCGAGGCCGAGGGCCA	20	1628
  BCL11A-1144	-	UGGCCGAGGCCGAGGGCCAC	20	1629
  BCL11A-1145	-	GGGCCACAGGGACACUUGCG	20	1630
  BCL11A-1146	-	CGACGAAGACUCGGUGGCCG	20	1631
  BCL11A-1147	-	AAGACUCGGUGGCCGGCGAG	20	1632
  BCL11A-1148	-	UUAAUGGCCGCGGCUGCUCC	20	1633
  BCL11A-1149	-	UGGCCGCGGCUGCUCCCCGG	20	1634
  BCL11A-1150	-	GCUCCCCGGGCGAGUCGGCC	20	1635
  BCL11A-1151	-	CUCCCCGGGCGAGUCGGCCU	20	1636
  BCL11A-1152	-	UCCCCGGGCGAGUCGGCCUC	20	1637
  BCL11A-1153	-	CCCCGGGCGAGUCGGCCUCG	20	1638
  BCL11A-1154	-	GCCUGUCCAAAAAGCUGCUG	20	1639
  BCL11A-1155	-	UGCUGGGCAGCCCCAGCUCG	20	1640
  BCL11A-1156	-	CUUCUCUAAGCGCAUCAAGC	20	1641
  BCL11A-1157	-	UCUCUAAGCGCAUCAAGCUC	20	1642
  BCL11A-1158	-	CUAAGCGCAUCAAGCUCGAG	20	1643
  BCL11A-1159	-	UAAGCGCAUCAAGCUCGAGA	20	1644
  BCL11A-1160	-	CCCCGGCCGCGAUGCCCAAC	20	1645
  BCL11A-1161	-	CCCGGCCGCGAUGCCCAACA	20	1646
  BCL11A-1162	-	CGGCCGCGAUGCCCAACACG	20	1647
  BCL11A-1163	-	CAAAGAUCCCUUCCUUAGCU	20	1648
  BCL11A-1164	-	AAAGAUCCCUUCCUUAGCUU	20	1649
  BCL11A-1165	-	AAUCGCCUUUUGCCUCCUCG	20	1650
  BCL11A-1166	-	AUCGCCUUUUGCCUCCUCGU	20	1651
  BCL11A-1167	-	CCUCCUCGUCGGAGCACUCC	20	1652
  BCL11A-1168	-	CUCCUCGUCGGAGCACUCCU	20	1653
  BCL11A-1169	-	CCUCGUCGGAGCACUCCUCG	20	1654
  BCL11A-1170	-	GUCGGAGCACUCCUCGGAGA	20	1655
  BCL11A-1171	-	UCGGAGCACUCCUCGGAGAA	20	1656
  BCL11A-1172	-	CGGAGCACUCCUCGGAGAAC	20	1657
  BCL11A-1173	-	UUUGCGCUUCUCCACACCGC	20	1658
  BCL11A-1174	-	UUGCGCUUCUCCACACCGCC	20	1659
  BCL11A-1175	-	UGCGCUUCUCCACACCGCCC	20	1660
  BCL11A-1176	-	GCGCUUCUCCACACCGCCCG	20	1661
  BCL11A-1177	-	UCUCCACACCGCCCGGGGAG	20	1662
  BCL11A-1178	-	CACACCGCCCGGGGAGCUGG	20	1663
  BCL11A-1179	-	ACACCGCCCGGGGAGCUGGA	20	1664
  BCL11A-1180	-	ACCGCCCGGGGAGCUGGACG	20	1665
  BCL11A-1181	-	CCGCCCGGGGAGCUGGACGG	20	1666
  BCL11A-1182	-	GGGAGCUGGACGGAGGGAUC	20	1667
  BCL11A-1183	-	GGAGCUGGACGGAGGGAUCU	20	1668
  BCL11A-1184	-	GGAUCUCGGGGCGCAGCGGC	20	1669
  BCL11A-1185	-	GAUCUCGGGGCGCAGCGGCA	20	1670
  BCL11A-1186	-	AUCUCGGGGCGCAGCGGCAC	20	1671
  BCL11A-1187	-	GGGGCGCAGCGGCACGGGAA	20	1672
  BCL11A-1188	-	GGGCGCAGCGGCACGGGAAG	20	1673
  BCL11A-1189	-	GCGCAGCGGCACGGGAAGUG	20	1674
  BCL11A-1190	-	CGCAGCGGCACGGGAAGUGG	20	1675
  BCL11A-1191	-	GCAGCGGCACGGGAAGUGGA	20	1676
  BCL11A-1192	-	GCACGCCCCAUAUUAGUGGU	20	1677
  BCL11A-1193	-	CCCAUAUUAGUGGUCCGGGC	20	1678
  BCL11A-1194	-	CCCGGGCAGGCCCAGCUCAA	20	1679
  BCL11A-1195	-	CGGGCAGGCCCAGCUCAAAA	20	1680
  BCL11A-1196	-	UUCUCUUGCAACACGCA	17	1681
  BCL11A-1197	-	ACACGCACAGAACACUC	17	1682
  BCL11A-1198	-	CAGAACACUCAUGGAUU	17	1683
  BCL11A-1199	-	UGGAUUAAGAAUCUACU	17	1684
  BCL11A-1200	-	AAGAAUCUACUUAGAAA	17	1685
  BCL11A-1201	-	CUACUUAGAAAGCGAAC	17	1686
  BCL11A-1202	-	UACUUAGAAAGCGAACA	17	1687
  BCL11A-1203	-	GGAAGUCCCCUGACCCC	17	1688
  BCL11A-1204	-	GCGGGUUGGUAUCCCUU	17	1689
  BCL11A-1205	-	CCCUUCAGGACUAGGUG	17	1690
  BCL11A-1206	-	UUCCCAGCCACCUCUCC	17	1691
  BCL11A-1207	-	UCCCAGCCACCUCUCCA	17	1692
  BCL11A-1208	-	AACCCCUUUAACCUGCU	17	1693
  BCL11A-1209	-	UAACCUGCUAAGAAUAC	17	1694
  BCL11A-1210	-	GAAUACCAGGAUCAGUA	17	1695
  BCL11A-1211	-	AUACCAGGAUCAGUAUC	17	1696
  BCL11A-1212	-	ACCAGGAUCAGUAUCGA	17	1697
  BCL11A-1213	-	AGAGGCUUCCGGCCUGG	17	1698
  BCL11A-1214	-	GGCUUCCGGCCUGGCAG	17	1699
  BCL11A-1215	-	CCCUGUUUAGUCCACCA	17	1700
  BCL11A-1216	-	CACCACCGAGACAUCAC	17	1701
  BCL11A-1217	-	CUUGGACCCCCACCGCA	17	1702
  BCL11A-1218	-	CCCACCGCAUAGAGCGC	17	1703
  BCL11A-1219	-	CCACCGCAUAGAGCGCC	17	1704
  BCL11A-1220	-	CACCGCAUAGAGCGCCU	17	1705
  BCL11A-1221	-	GCAUAGAGCGCCUGGGG	17	1706
  BCL11A-1222	-	CAUAGAGCGCCUGGGGG	17	1707
  BCL11A-1223	-	AGAGCGCCUGGGGGCGG	17	1708
  BCL11A-1224	-	CCCUGGCCACCCAUCAC	17	1709
  BCL11A-1225	-	CACCCGAGUGCCUUUGA	17	1710
  BCL11A-1226	-	UUGACAGGGUGCUGCGG	17	1711
  BCL11A-1227	-	GGUUGAAUCCAAUGGCU	17	1712
  BCL11A-1228	-	GUUGAAUCCAAUGGCUA	17	1713
  BCL11A-1229	-	CUAUGGAGCCUCCCGCC	17	1714
  BCL11A-1230	-	CCCGCCAUGGAUUUCUC	17	1715
  BCL11A-1231	-	CCGCCAUGGAUUUCUCU	17	1716
  BCL11A-1232	-	GAUUUCUCUAGGAGACU	17	1717
  BCL11A-1233	-	UUUCUCUAGGAGACUUA	17	1718
  BCL11A-1234	-	GAGACUUAGAGAGCUGG	17	1719
  BCL11A-1235	-	AGACUUAGAGAGCUGGC	17	1720
  BCL11A-1236	-	GACUUAGAGAGCUGGCA	17	1721
  BCL11A-1237	-	GGUCAAGUCCAAGUCAU	17	1722
  BCL11A-1238	-	GCAAGACGUUCAAAUUU	17	1723
  BCL11A-1239	-	UGCACCGGCGCAGCCAC	17	1724
  BCL11A-1240	-	CCGGCGCAGCCACACGG	17	1725
  BCL11A-1241	-	GGCGCAGCCACACGGGC	17	1726
  BCL11A-1242	-	GCACCCAGGCCAGCAAG	17	1727
  BCL11A-1243	-	GCAAGCUGAAGCGCCAC	17	1728
  BCL11A-1244	-	UCUCCACCGCCAGCUCC	17	1729
  BCL11A-1245	-	CUCCACCGCCAGCUCCC	17	1730
  BCL11A-1246	-	CCGGCACCAGCGACUUG	17	1731
  BCL11A-1247	-	CCGUGGUGGCCAAGUUC	17	1732
  BCL11A-1248	-	GGUGGCCAAGUUCAAGA	17	1733
  BCL11A-1249	-	UGGCCAAGUUCAAGAGC	17	1734
  BCL11A-1250	-	ACGACCCCAACCUGAUC	17	1735
  BCL11A-1251	-	CGACCCCAACCUGAUCC	17	1736
  BCL11A-1252	-	ACCCCAACCUGAUCCCG	17	1737
  BCL11A-1253	-	CAACCUGAUCCCGGAGA	17	1738
  BCL11A-1254	-	AACCUGAUCCCGGAGAA	17	1739
  BCL11A-1255	-	ACCUGAUCCCGGAGAAC	17	1740
  BCL11A-1256	-	GAUCCCGGAGAACGGGG	17	1741
  BCL11A-1257	-	UCCCGGAGAACGGGGAC	17	1742
  BCL11A-1258	-	CCCGGAGAACGGGGACG	17	1743
  BCL11A-1259	-	CGGAGAACGGGGACGAG	17	1744
  BCL11A-1260	-	GGAGAACGGGGACGAGG	17	1745
  BCL11A-1261	-	GAACGGGGACGAGGAGG	17	1746
  BCL11A-1262	-	ACGGGGACGAGGAGGAA	17	1747
  BCL11A-1263	-	CGGGGACGAGGAGGAAG	17	1748
  BCL11A-1264	-	GGGACGAGGAGGAAGAG	17	1749
  BCL11A-1265	-	GGAGGAAGAGGAGGACG	17	1750
  BCL11A-1266	-	AGGAAGAGGAGGACGAC	17	1751
  BCL11A-1267	-	GGAAGAGGAGGACGACG	17	1752
  BCL11A-1268	-	AGAGGAGGACGACGAGG	17	1753
  BCL11A-1269	-	AGGAGGACGACGAGGAA	17	1754
  BCL11A-1270	-	GGAGGACGACGAGGAAG	17	1755
  BCL11A-1271	-	GGACGACGAGGAAGAGG	17	1756
  BCL11A-1272	-	CGACGAGGAAGAGGAAG	17	1757
  BCL11A-1273	-	ACGAGGAAGAGGAAGAA	17	1758
  BCL11A-1274	-	CGAGGAAGAGGAAGAAG	17	1759
  BCL11A-1275	-	AGGAAGAGGAAGAAGAG	17	1760
  BCL11A-1276	-	GGAAGAGGAAGAAGAGG	17	1761
  BCL11A-1277	-	AGAGGAAGAAGAGGAGG	17	1762
  BCL11A-1278	-	AGGAAGAAGAGGAGGAA	17	1763
  BCL11A-1279	-	GGAAGAAGAGGAGGAAG	17	1764
  BCL11A-1280	-	AAGAAGAGGAGGAAGAG	17	1765
  BCL11A-1281	-	AGAAGAGGAGGAAGAGG	17	1766
  BCL11A-1282	-	AAGAGGAGGAAGAGGAG	17	1767
  BCL11A-1283	-	AGAGGAGGAAGAGGAGG	17	1768
  BCL11A-1284	-	AGGAGGAAGAGGAGGAG	17	1769
  BCL11A-1285	-	GGAGGAAGAGGAGGAGG	17	1770
  BCL11A-1286	-	AGGAGGAGGAGGAGCUG	17	1771
  BCL11A-1287	-	GGAGGAGGAGGAGCUGA	17	1772
  BCL11A-1288	-	AGGAGGAGGAGCUGACG	17	1773
  BCL11A-1289	-	GGAGGAGCUGACGGAGA	17	1774
  BCL11A-1290	-	AGGAGCUGACGGAGAGC	17	1775
  BCL11A-1291	-	GAGCUGACGGAGAGCGA	17	1776
  BCL11A-1292	-	UGACGGAGAGCGAGAGG	17	1777
  BCL11A-1293	-	GAGGGUGGACUACGGCU	17	1778
  BCL11A-1294	-	UGGACUACGGCUUCGGG	17	1779
  BCL11A-1295	-	ACGGCUUCGGGCUGAGC	17	1780
  BCL11A-1296	-	CGGCUUCGGGCUGAGCC	17	1781
  BCL11A-1297	-	GGAGGCGGCGCGCCACC	17	1782
  BCL11A-1298	-	AGGCGGCGCGCCACCAC	17	1783
  BCL11A-1299	-	CACCACGAGAACAGCUC	17	1784
  BCL11A-1300	-	ACCACGAGAACAGCUCG	17	1785
  BCL11A-1301	-	GCUCGCGGGGCGCGGUC	17	1786
  BCL11A-1302	-	GGGGCGCGGUCGUGGGC	17	1787
  BCL11A-1303	-	GGUCGUGGGCGUGGGCG	17	1788
  BCL11A-1304	-	UCGUGGGCGUGGGCGAC	17	1789
  BCL11A-1305	-	CCCUGCCCGACGUCAUG	17	1790
  BCL11A-1306	-	CUCCAUGCAGCACUUCA	17	1791
  BCL11A-1307	-	AGGCCUUCCACCAGGUC	17	1792
  BCL11A-1308	-	CUUCCACCAGGUCCUGG	17	1793
  BCL11A-1309	-	UCCACCAGGUCCUGGGC	17	1794
  BCL11A-1310	-	UAAGCGCGGCCACCUGG	17	1795
  BCL11A-1311	-	CGGCCACCUGGCCGAGG	17	1796
  BCL11A-1312	-	GCCACCUGGCCGAGGCC	17	1797
  BCL11A-1313	-	GCCGAGGCCGAGGGCCA	17	1798
  BCL11A-1314	-	CCGAGGCCGAGGGCCAC	17	1799
  BCL11A-1315	-	CCACAGGGACACUUGCG	17	1800
  BCL11A-1316	-	CGAAGACUCGGUGGCCG	17	1801
  BCL11A-1317	-	ACUCGGUGGCCGGCGAG	17	1802
  BCL11A-1318	-	AUGGCCGCGGCUGCUCC	17	1803
  BCL11A-1319	-	CCGCGGCUGCUCCCCGG	17	1804
  BCL11A-1320	-	CCCCGGGCGAGUCGGCC	17	1805
  BCL11A-1321	-	CCCGGGCGAGUCGGCCU	17	1806
  BCL11A-1322	-	CCGGGCGAGUCGGCCUC	17	1807
  BCL11A-1323	-	CGGGCGAGUCGGCCUCG	17	1808
  BCL11A-1324	-	UGUCCAAAAAGCUGCUG	17	1809
  BCL11A-1325	-	UGGGCAGCCCCAGCUCG	17	1810
  BCL11A-1326	-	CUCUAAGCGCAUCAAGC	17	1811
  BCL11A-1327	-	CUAAGCGCAUCAAGCUC	17	1812
  BCL11A-1328	-	AGCGCAUCAAGCUCGAG	17	1813
  BCL11A-1329	-	GCGCAUCAAGCUCGAGA	17	1814
  BCL11A-1330	-	CGGCCGCGAUGCCCAAC	17	1815
  BCL11A-1331	-	GGCCGCGAUGCCCAACA	17	1816
  BCL11A-1332	-	CCGCGAUGCCCAACACG	17	1817
  BCL11A-1333	-	AGAUCCCUUCCUUAGCU	17	1818
  BCL11A-1334	-	GAUCCCUUCCUUAGCUU	17	1819
  BCL11A-1335	-	CGCCUUUUGCCUCCUCG	17	1820
  BCL11A-1336	-	GCCUUUUGCCUCCUCGU	17	1821
  BCL11A-1337	-	CCUCGUCGGAGCACUCC	17	1822
  BCL11A-1338	-	CUCGUCGGAGCACUCCU	17	1823
  BCL11A-1339	-	CGUCGGAGCACUCCUCG	17	1824
  BCL11A-1340	-	GGAGCACUCCUCGGAGA	17	1825
  BCL11A-1341	-	GAGCACUCCUCGGAGAA	17	1826
  BCL11A-1342	-	AGCACUCCUCGGAGAAC	17	1827
  BCL11A-1343	-	GCGCUUCUCCACACCGC	17	1828
  BCL11A-1344	-	CGCUUCUCCACACCGCC	17	1829
  BCL11A-1345	-	GCUUCUCCACACCGCCC	17	1830
  BCL11A-1346	-	CUUCUCCACACCGCCCG	17	1831
  BCL11A-1347	-	CCACACCGCCCGGGGAG	17	1832
  BCL11A-1348	-	ACCGCCCGGGGAGCUGG	17	1833
  BCL11A-1349	-	CCGCCCGGGGAGCUGGA	17	1834
  BCL11A-1350	-	GCCCGGGGAGCUGGACG	17	1835
  BCL11A-1351	-	CCCGGGGAGCUGGACGG	17	1836
  BCL11A-1352	-	AGCUGGACGGAGGGAUC	17	1837
  BCL11A-1353	-	GCUGGACGGAGGGAUCU	17	1838
  BCL11A-1354	-	UCUCGGGGCGCAGCGGC	17	1839
  BCL11A-1355	-	CUCGGGGCGCAGCGGCA	17	1840
  BCL11A-1356	-	UCGGGGCGCAGCGGCAC	17	1841
  BCL11A-1357	-	GCGCAGCGGCACGGGAA	17	1842
  BCL11A-1358	-	CGCAGCGGCACGGGAAG	17	1843
  BCL11A-1359	-	CAGCGGCACGGGAAGUG	17	1844
  BCL11A-1360	-	AGCGGCACGGGAAGUGG	17	1845
  BCL11A-1361	-	GCGGCACGGGAAGUGGA	17	1846
  BCL11A-1362	-	CGCCCCAUAUUAGUGGU	17	1847
  BCL11A-1363	-	AUAUUAGUGGUCCGGGC	17	1848
  BCL11A-1364	-	GGGCAGGCCCAGCUCAA	17	1849
  BCL11A-1365	-	GCAGGCCCAGCUCAAAA	17	1850
  BCL11A-1366	+	AAGUUGUACAUGUGUAGCUG	20	1851
  BCL11A-1367	+	GCAAGAGAAACCAUGCACUG	20	1852
  BCL11A-1368	+	GUGUUCUGUGCGUGUUGCAA	20	1853
  BCL11A-1369	+	GAGUGUUCUGUGCGUGUUGC	20	1854
  BCL11A-1370	+	UCUAAGUAGAUUCUUAAUCC	20	1855
  BCL11A-1371	+	GAUACCAACCCGCGGGGUCA	20	1856
  BCL11A-1372	+	GGAUACCAACCCGCGGGGUC	20	1857
  BCL11A-1373	+	GGGAUACCAACCCGCGGGGU	20	1858
  BCL11A-1374	+	CCUGAAGGGAUACCAACCCG	20	1859
  BCL11A-1375	+	UCCUGAAGGGAUACCAACCC	20	1860
  BCL11A-1376	+	CAUUCUGCACCUAGUCCUGA	20	1861
  BCL11A-1377	+	ACAUUCUGCACCUAGUCCUG	20	1862
  BCL11A-1378	+	AGGACAUUCUGCACCUAGUC	20	1863
  BCL11A-1379	+	CCCAUGGAGAGGUGGCUGGG	20	1864
  BCL11A-1380	+	AAUCCCAUGGAGAGGUGGCU	20	1865
  BCL11A-1381	+	GAAUCCCAUGGAGAGGUGGC	20	1866
  BCL11A-1382	+	UGAAUCCCAUGGAGAGGUGG	20	1867
  BCL11A-1383	+	UCUGCAAUAUGAAUCCCAUG	20	1868
  BCL11A-1384	+	UGUCUGCAAUAUGAAUCCCA	20	1869
  BCL11A-1385	+	UUGUCUGCAAUAUGAAUCCC	20	1870
  BCL11A-1386	+	AAGGGGUUAUUGUCUGCAAU	20	1871
  BCL11A-1387	+	UGGUAUUCUUAGCAGGUUAA	20	1872
  BCL11A-1388	+	CUGGUAUUCUUAGCAGGUUA	20	1873
  BCL11A-1389	+	AAAGCGCCCUUCUGCCAGGC	20	1874
  BCL11A-1390	+	GAAAGCGCCCUUCUGCCAGG	20	1875
  BCL11A-1391	+	CUAAACAGGGGGGGAGUGGG	20	1876
  BCL11A-1392	+	ACUAAACAGGGGGGGAGUGG	20	1877
  BCL11A-1393	+	GUGGACUAAACAGGGGGGGA	20	1878
  BCL11A-1394	+	GGUGGUGGACUAAACAGGGG	20	1879
  BCL11A-1395	+	CGGUGGUGGACUAAACAGGG	20	1880
  BCL11A-1396	+	UCGGUGGUGGACUAAACAGG	20	1881
  BCL11A-1397	+	CUCGGUGGUGGACUAAACAG	20	1882
  BCL11A-1398	+	UCUCGGUGGUGGACUAAACA	20	1883
  BCL11A-1399	+	GUCUCGGUGGUGGACUAAAC	20	1884
  BCL11A-1400	+	UGUCUCGGUGGUGGACUAAA	20	1885
  BCL11A-1401	+	GUCCAAGUGAUGUCUCGGUG	20	1886
  BCL11A-1402	+	CCCCAGGCGCUCUAUGCGGU	20	1887
  BCL11A-1403	+	CCCCCAGGCGCUCUAUGCGG	20	1888
  BCL11A-1404	+	GCCCCCAGGCGCUCUAUGCG	20	1889
  BCL11A-1405	+	GCACUCGGGUGAUGGGUGGC	20	1890
  BCL11A-1406	+	CUGUCAAAGGCACUCGGGUG	20	1891
  BCL11A-1407	+	CAGCACCCUGUCAAAGGCAC	20	1892
  BCL11A-1408	+	GGCGGGAGGCUCCAUAGCCA	20	1893
  BCL11A-1409	+	CUCCUAGAGAAAUCCAUGGC	20	1894
  BCL11A-1410	+	UCUCCUAGAGAAAUCCAUGG	20	1895
  BCL11A-1411	+	GUCUCCUAGAGAAAUCCAUG	20	1896
  BCL11A-1412	+	CCAGCUCUCUAAGUCUCCUA	20	1897
  BCL11A-1413	+	UGCCAGCUCUCUAAGUCUCC	20	1898
  BCL11A-1414	+	GGGCCGGCCUGGGGACAGCG	20	1899
  BCL11A-1415	+	GCAUAGGGCUGGGCCGGCCU	20	1900
  BCL11A-1416	+	UGCAUAGGGCUGGGCCGGCC	20	1901
  BCL11A-1417	+	UUGCAUAGGGCUGGGCCGGC	20	1902
  BCL11A-1418	+	GCAGUAACCUUUGCAUAGGG	20	1903
  BCL11A-1419	+	UGGUUGCAGUAACCUUUGCA	20	1904
  BCL11A-1420	+	AGGGCGGCUUGCUACCUGGC	20	1905
  BCL11A-1421	+	AAGGGCGGCUUGCUACCUGG	20	1906
  BCL11A-1422	+	GGAGGGGGGGCGUCGCCAGG	20	1907
  BCL11A-1423	+	GAGGGAGGGGGGGCGUCGCC	20	1908
  BCL11A-1424	+	GGAGGGAGGGGGGGCGUCGC	20	1909
  BCL11A-1425	+	CGGAUUGCAGAGGAGGGAGG	20	1910
  BCL11A-1426	+	GCGGAUUGCAGAGGAGGGAG	20	1911
  BCL11A-1427	+	GGCGGAUUGCAGAGGAGGGA	20	1912
  BCL11A-1428	+	GGGCGGAUUGCAGAGGAGGG	20	1913
  BCL11A-1429	+	GGGGCGGAUUGCAGAGGAGG	20	1914
  BCL11A-1430	+	GAGGGGCGGAUUGCAGAGGA	20	1915
  BCL11A-1431	+	GGAGGGGCGGAUUGCAGAGG	20	1916
  BCL11A-1432	+	AGGAGGGGCGGAUUGCAGAG	20	1917
  BCL11A-1433	+	GGAGGAGGGGCGGAUUGCAG	20	1918
  BCL11A-1434	+	GGGAGGAGGGGCGGAUUGCA	20	1919
  BCL11A-1435	+	GAGGGAGGAGGGGCGGAUUG	20	1920
  BCL11A-1436	+	GGGGCUGGGAGGGAGGAGGG	20	1921
  BCL11A-1437	+	ACCGGGGGCUGGGAGGGAGG	20	1922
  BCL11A-1438	+	GACCGGGGGCUGGGAGGGAG	20	1923
  BCL11A-1439	+	UUGACCGGGGGCUGGGAGGG	20	1924
  BCL11A-1440	+	CUUGACCGGGGGCUGGGAGG	20	1925
  BCL11A-1441	+	GACUUGACCGGGGGCUGGGA	20	1926
  BCL11A-1442	+	GGACUUGACCGGGGGCUGGG	20	1927
  BCL11A-1443	+	UGGACUUGACCGGGGGCUGG	20	1928
  BCL11A-1444	+	CUUGGACUUGACCGGGGGCU	20	1929
  BCL11A-1445	+	ACUUGGACUUGACCGGGGGC	20	1930
  BCL11A-1446	+	GACUUGGACUUGACCGGGGG	20	1931
  BCL11A-1447	+	CGCAUGACUUGGACUUGACC	20	1932
  BCL11A-1448	+	UCGCAUGACUUGGACUUGAC	20	1933
  BCL11A-1449	+	CUCGCAUGACUUGGACUUGA	20	1934
  BCL11A-1450	+	UGCCGCAGAACUCGCAUGAC	20	1935
  BCL11A-1451	+	GAAAUUUGAACGUCUUGCCG	20	1936
  BCL11A-1452	+	CCACCAGGUUGCUCUGAAAU	20	1937
  BCL11A-1453	+	CGGUGCACCACCAGGUUGCU	20	1938
  BCL11A-1454	+	GGUCGCACAGGUUGCACUUG	20	1939
  BCL11A-1455	+	UGGCGCUUCAGCUUGCUGGC	20	1940
  BCL11A-1456	+	CGUCGGACUUGACCGUCAUG	20	1941
  BCL11A-1457	+	UCGUCGGACUUGACCGUCAU	20	1942
  BCL11A-1458	+	GUCGUCGGACUUGACCGUCA	20	1943
  BCL11A-1459	+	CGUCGUCGGACUUGACCGUC	20	1944
  BCL11A-1460	+	UGGCGGUGGAGAGACCGUCG	20	1945
  BCL11A-1461	+	GUUCCGGGGAGCUGGCGGUG	20	1946
  BCL11A-1462	+	GGGUUCCGGGGAGCUGGCGG	20	1947
  BCL11A-1463	+	CGGGUUCCGGGGAGCUGGCG	20	1948
  BCL11A-1464	+	GUCGCUGGUGCCGGGUUCCG	20	1949
  BCL11A-1465	+	AGUCGCUGGUGCCGGGUUCC	20	1950
  BCL11A-1466	+	AAGUCGCUGGUGCCGGGUUC	20	1951
  BCL11A-1467	+	CAAGUCGCUGGUGCCGGGUU	20	1952
  BCL11A-1468	+	UGCCCACCAAGUCGCUGGUG	20	1953
  BCL11A-1469	+	UGAACUUGGCCACCACGGAC	20	1954
  BCL11A-1470	+	CGCUCUUGAACUUGGCCACC	20	1955
  BCL11A-1471	+	GGUUGGGGUCGUUCUCGCUC	20	1956
  BCL11A-1472	+	CCCGUUCUCCGGGAUCAGGU	20	1957
  BCL11A-1473	+	CCCCGUUCUCCGGGAUCAGG	20	1958
  BCL11A-1474	+	UCCUCCUCGUCCCCGUUCUC	20	1959
  BCL11A-1475	+	UUCCUCCUCGUCCCCGUUCU	20	1960
  BCL11A-1476	+	GCGCCGCCUCCAGGCUCAGC	20	1961
  BCL11A-1477	+	CACGCCCACGACCGCGCCCC	20	1962
  BCL11A-1478	+	AUGCCCUGCAUGACGUCGGG	20	1963
  BCL11A-1479	+	GCACCAUGCCCUGCAUGACG	20	1964
  BCL11A-1480	+	CGCUGAAGUGCUGCAUGGAG	20	1965
  BCL11A-1481	+	GGCCUCGCUGAAGUGCUGCA	20	1966
  BCL11A-1482	+	AGGCCUCGCUGAAGUGCUGC	20	1967
  BCL11A-1483	+	GGACCUGGUGGAAGGCCUCG	20	1968
  BCL11A-1484	+	GCUUCUCGCCCAGGACCUGG	20	1969
  BCL11A-1485	+	UGCUUCUCGCCCAGGACCUG	20	1970
  BCL11A-1486	+	CCGCGCUUAUGCUUCUCGCC	20	1971
  BCL11A-1487	+	GCGGUCCGACUCGCCGGCCA	20	1972
  BCL11A-1488	+	CCCCGAGGCCGACUCGCCCG	20	1973
  BCL11A-1489	+	CCCCCGAGGCCGACUCGCCC	20	1974
  BCL11A-1490	+	CCCCCCGAGGCCGACUCGCC	20	1975
  BCL11A-1491	+	GCCCCCCGAGGCCGACUCGC	20	1976
  BCL11A-1492	+	CAGCUUUUUGGACAGGCCCC	20	1977
  BCL11A-1493	+	GGCUGCCCAGCAGCAGCUUU	20	1978
  BCL11A-1494	+	AGAGAAGGGGCUCAGCGAGC	20	1979
  BCL11A-1495	+	UAGAGAAGGGGCUCAGCGAG	20	1980
  BCL11A-1496	+	GCGCUUAGAGAAGGGGCUCA	20	1981
  BCL11A-1497	+	GAGCUUGAUGCGCUUAGAGA	20	1982
  BCL11A-1498	+	CGAGCUUGAUGCGCUUAGAG	20	1983
  BCL11A-1499	+	UCUCGAGCUUGAUGCGCUUA	20	1984
  BCL11A-1500	+	CUUCUCGAGCUUGAUGCGCU	20	1985
  BCL11A-1501	+	GGGGCAGGUCGAACUCCUUC	20	1986
  BCL11A-1502	+	GCAUCGCGGCCGGGGGCAGG	20	1987
  BCL11A-1503	+	CCGUGUUGGGCAUCGCGGCC	20	1988
  BCL11A-1504	+	UCCGUGUUGGGCAUCGCGGC	20	1989
  BCL11A-1505	+	CUCCGUGUUGGGCAUCGCGG	20	1990
  BCL11A-1506	+	GCGAGUACACGUUCUCCGUG	20	1991
  BCL11A-1507	+	CGCGUAGCCGGCGAGCCACU	20	1992
  BCL11A-1508	+	GCCUGGAGGCCGCGUAGCCG	20	1993
  BCL11A-1509	+	GAAGGGAUCUUUGAGCUGCC	20	1994
  BCL11A-1510	+	GGAAGGGAUCUUUGAGCUGC	20	1995
  BCL11A-1511	+	CGAAGCUAAGGAAGGGAUCU	20	1996
  BCL11A-1512	+	GGAGUCUCCGAAGCUAAGGA	20	1997
  BCL11A-1513	+	UGGAGUCUCCGAAGCUAAGG	20	1998
  BCL11A-1514	+	GUCUGGAGUCUCCGAAGCUA	20	1999
  BCL11A-1515	+	UGUCUGGAGUCUCCGAAGCU	20	2000
  BCL11A-1516	+	AAGGCGAUUGUCUGGAGUCU	20	2001
  BCL11A-1517	+	GGAGGCAAAAGGCGAUUGUC	20	2002
  BCL11A-1518	+	AGGAGGCAAAAGGCGAUUGU	20	2003
  BCL11A-1519	+	CUCCGAGGAGUGCUCCGACG	20	2004
  BCL11A-1520	+	UCUCCGAGGAGUGCUCCGAC	20	2005
  BCL11A-1521	+	GUUCUCCGAGGAGUGCUCCG	20	2006
  BCL11A-1522	+	GCGCAAACUCCCGUUCUCCG	20	2007
  BCL11A-1523	+	AGCGCAAACUCCCGUUCUCC	20	2008
  BCL11A-1524	+	GAAGCGCAAACUCCCGUUCU	20	2009
  BCL11A-1525	+	CCAGCUCCCCGGGCGGUGUG	20	2010
  BCL11A-1526	+	GUCCAGCUCCCCGGGCGGUG	20	2011
  BCL11A-1527	+	CGUCCAGCUCCCCGGGCGGU	20	2012
  BCL11A-1528	+	AGAUCCCUCCGUCCAGCUCC	20	2013
  BCL11A-1529	+	ACUUCCCGUGCCGCUGCGCC	20	2014
  BCL11A-1530	+	CCGGGCCCGGACCACUAAUA	20	2015
  BCL11A-1531	+	CCCGGGCCCGGACCACUAAU	20	2016
  BCL11A-1532	+	UGAGCUGGGCCUGCCCGGGC	20	2017
  BCL11A-1533	+	CUCUUUUGAGCUGGGCCUGC	20	2018
  BCL11A-1534	+	UGCGUCUGCCCUCUUUUGAG	20	2019
  BCL11A-1535	+	GUCGCUGCGUCUGCCCUCUU	20	2020
  BCL11A-1536	+	UUGUACAUGUGUAGCUG	17	2021
  BCL11A-1537	+	AGAGAAACCAUGCACUG	17	2022
  BCL11A-1538	+	UUCUGUGCGUGUUGCAA	17	2023
  BCL11A-1539	+	UGUUCUGUGCGUGUUGC	17	2024
  BCL11A-1540	+	AAGUAGAUUCUUAAUCC	17	2025
  BCL11A-1541	+	ACCAACCCGCGGGGUCA	17	2026
  BCL11A-1542	+	UACCAACCCGCGGGGUC	17	2027
  BCL11A-1543	+	AUACCAACCCGCGGGGU	17	2028
  BCL11A-1544	+	GAAGGGAUACCAACCCG	17	2029
  BCL11A-1545	+	UGAAGGGAUACCAACCC	17	2030
  BCL11A-1546	+	UCUGCACCUAGUCCUGA	17	2031
  BCL11A-1547	+	UUCUGCACCUAGUCCUG	17	2032
  BCL11A-1548	+	ACAUUCUGCACCUAGUC	17	2033
  BCL11A-1549	+	AUGGAGAGGUGGCUGGG	17	2034
  BCL11A-1550	+	CCCAUGGAGAGGUGGCU	17	2035
  BCL11A-1551	+	UCCCAUGGAGAGGUGGC	17	2036
  BCL11A-1552	+	AUCCCAUGGAGAGGUGG	17	2037
  BCL11A-1553	+	GCAAUAUGAAUCCCAUG	17	2038
  BCL11A-1554	+	CUGCAAUAUGAAUCCCA	17	2039
  BCL11A-1555	+	UCUGCAAUAUGAAUCCC	17	2040
  BCL11A-1556	+	GGGUUAUUGUCUGCAAU	17	2041
  BCL11A-1557	+	UAUUCUUAGCAGGUUAA	17	2042
  BCL11A-1558	+	GUAUUCUUAGCAGGUUA	17	2043
  BCL11A-1559	+	GCGCCCUUCUGCCAGGC	17	2044
  BCL11A-1560	+	AGCGCCCUUCUGCCAGG	17	2045
  BCL11A-1561	+	AACAGGGGGGGAGUGGG	17	2046
  BCL11A-1562	+	AAACAGGGGGGGAGUGG	17	2047
  BCL11A-1563	+	GACUAAACAGGGGGGGA	17	2048
  BCL11A-1564	+	GGUGGACUAAACAGGGG	17	2049
  BCL11A-1565	+	UGGUGGACUAAACAGGG	17	2050
  BCL11A-1566	+	GUGGUGGACUAAACAGG	17	2051
  BCL11A-1567	+	GGUGGUGGACUAAACAG	17	2052
  BCL11A-1568	+	CGGUGGUGGACUAAACA	17	2053
  BCL11A-1569	+	UCGGUGGUGGACUAAAC	17	2054
  BCL11A-1570	+	CUCGGUGGUGGACUAAA	17	2055
  BCL11A-1571	+	CAAGUGAUGUCUCGGUG	17	2056
  BCL11A-1572	+	CAGGCGCUCUAUGCGGU	17	2057
  BCL11A-1573	+	CCAGGCGCUCUAUGCGG	17	2058
  BCL11A-1574	+	CCCAGGCGCUCUAUGCG	17	2059
  BCL11A-1575	+	CUCGGGUGAUGGGUGGC	17	2060
  BCL11A-1576	+	UCAAAGGCACUCGGGUG	17	2061
  BCL11A-1577	+	CACCCUGUCAAAGGCAC	17	2062
  BCL11A-1578	+	GGGAGGCUCCAUAGCCA	17	2063
  BCL11A-1579	+	CUAGAGAAAUCCAUGGC	17	2064
  BCL11A-1580	+	CCUAGAGAAAUCCAUGG	17	2065
  BCL11A-1581	+	UCCUAGAGAAAUCCAUG	17	2066
  BCL11A-1582	+	GCUCUCUAAGUCUCCUA	17	2067
  BCL11A-1583	+	CAGCUCUCUAAGUCUCC	17	2068
  BCL11A-1584	+	CCGGCCUGGGGACAGCG	17	2069
  BCL11A-1585	+	UAGGGCUGGGCCGGCCU	17	2070
  BCL11A-1586	+	AUAGGGCUGGGCCGGCC	17	2071
  BCL11A-1587	+	CAUAGGGCUGGGCCGGC	17	2072
  BCL11A-1588	+	GUAACCUUUGCAUAGGG	17	2073
  BCL11A-1589	+	UUGCAGUAACCUUUGCA	17	2074
  BCL11A-1590	+	GCGGCUUGCUACCUGGC	17	2075
  BCL11A-1591	+	GGCGGCUUGCUACCUGG	17	2076
  BCL11A-1592	+	GGGGGGGCGUCGCCAGG	17	2077
  BCL11A-1593	+	GGAGGGGGGGCGUCGCC	17	2078
  BCL11A-1594	+	GGGAGGGGGGGCGUCGC	17	2079
  BCL11A-1595	+	AUUGCAGAGGAGGGAGG	17	2080
  BCL11A-1596	+	GAUUGCAGAGGAGGGAG	17	2081
  BCL11A-1597	+	GGAUUGCAGAGGAGGGA	17	2082
  BCL11A-1598	+	CGGAUUGCAGAGGAGGG	17	2083
  BCL11A-1599	+	GCGGAUUGCAGAGGAGG	17	2084
  BCL11A-1600	+	GGGCGGAUUGCAGAGGA	17	2085
  BCL11A-1601	+	GGGGCGGAUUGCAGAGG	17	2086
  BCL11A-1602	+	AGGGGCGGAUUGCAGAG	17	2087
  BCL11A-1603	+	GGAGGGGCGGAUUGCAG	17	2088
  BCL11A-1604	+	AGGAGGGGCGGAUUGCA	17	2089
  BCL11A-1605	+	GGAGGAGGGGCGGAUUG	17	2090
  BCL11A-1606	+	GCUGGGAGGGAGGAGGG	17	2091
  BCL11A-1607	+	GGGGGCUGGGAGGGAGG	17	2092
  BCL11A-1608	+	CGGGGGCUGGGAGGGAG	17	2093
  BCL11A-1609	+	ACCGGGGGCUGGGAGGG	17	2094
  BCL11A-1610	+	GACCGGGGGCUGGGAGG	17	2095
  BCL11A-1611	+	UUGACCGGGGGCUGGGA	17	2096
  BCL11A-1612	+	CUUGACCGGGGGCUGGG	17	2097
  BCL11A-1613	+	ACUUGACCGGGGGCUGG	17	2098
  BCL11A-1614	+	GGACUUGACCGGGGGCU	17	2099
  BCL11A-1615	+	UGGACUUGACCGGGGGC	17	2100
  BCL11A-1616	+	UUGGACUUGACCGGGGG	17	2101
  BCL11A-1617	+	AUGACUUGGACUUGACC	17	2102
  BCL11A-1618	+	CAUGACUUGGACUUGAC	17	2103
  BCL11A-1619	+	GCAUGACUUGGACUUGA	17	2104
  BCL11A-1620	+	CGCAGAACUCGCAUGAC	17	2105
  BCL11A-1621	+	AUUUGAACGUCUUGCCG	17	2106
  BCL11A-1622	+	CCAGGUUGCUCUGAAAU	17	2107
  BCL11A-1623	+	UGCACCACCAGGUUGCU	17	2108
  BCL11A-1624	+	CGCACAGGUUGCACUUG	17	2109
  BCL11A-1625	+	CGCUUCAGCUUGCUGGC	17	2110
  BCL11A-1626	+	CGGACUUGACCGUCAUG	17	2111
  BCL11A-1627	+	UCGGACUUGACCGUCAU	17	2112
  BCL11A-1628	+	GUCGGACUUGACCGUCA	17	2113
  BCL11A-1629	+	CGUCGGACUUGACCGUC	17	2114
  BCL11A-1630	+	CGGUGGAGAGACCGUCG	17	2115
  BCL11A-1631	+	CCGGGGAGCUGGCGGUG	17	2116
  BCL11A-1632	+	UUCCGGGGAGCUGGCGG	17	2117
  BCL11A-1633	+	GUUCCGGGGAGCUGGCG	17	2118
  BCL11A-1634	+	GCUGGUGCCGGGUUCCG	17	2119
  BCL11A-1635	+	CGCUGGUGCCGGGUUCC	17	2120
  BCL11A-1636	+	UCGCUGGUGCCGGGUUC	17	2121
  BCL11A-1637	+	GUCGCUGGUGCCGGGUU	17	2122
  BCL11A-1638	+	CCACCAAGUCGCUGGUG	17	2123
  BCL11A-1639	+	ACUUGGCCACCACGGAC	17	2124
  BCL11A-1640	+	UCUUGAACUUGGCCACC	17	2125
  BCL11A-1641	+	UGGGGUCGUUCUCGCUC	17	2126
  BCL11A-1642	+	GUUCUCCGGGAUCAGGU	17	2127
  BCL11A-1643	+	CGUUCUCCGGGAUCAGG	17	2128
  BCL11A-1644	+	UCCUCGUCCCCGUUCUC	17	2129
  BCL11A-1645	+	CUCCUCGUCCCCGUUCU	17	2130
  BCL11A-1646	+	CCGCCUCCAGGCUCAGC	17	2131
  BCL11A-1647	+	GCCCACGACCGCGCCCC	17	2132
  BCL11A-1648	+	CCCUGCAUGACGUCGGG	17	2133
  BCL11A-1649	+	CCAUGCCCUGCAUGACG	17	2134
  BCL11A-1650	+	UGAAGUGCUGCAUGGAG	17	2135
  BCL11A-1651	+	CUCGCUGAAGUGCUGCA	17	2136
  BCL11A-1652	+	CCUCGCUGAAGUGCUGC	17	2137
  BCL11A-1653	+	CCUGGUGGAAGGCCUCG	17	2138
  BCL11A-1654	+	UCUCGCCCAGGACCUGG	17	2139
  BCL11A-1655	+	UUCUCGCCCAGGACCUG	17	2140
  BCL11A-1656	+	CGCUUAUGCUUCUCGCC	17	2141
  BCL11A-1657	+	GUCCGACUCGCCGGCCA	17	2142
  BCL11A-1658	+	CGAGGCCGACUCGCCCG	17	2143
  BCL11A-1659	+	CCGAGGCCGACUCGCCC	17	2144
  BCL11A-1660	+	CCCGAGGCCGACUCGCC	17	2145
  BCL11A-1661	+	CCCCGAGGCCGACUCGC	17	2146
  BCL11A-1662	+	CUUUUUGGACAGGCCCC	17	2147
  BCL11A-1663	+	UGCCCAGCAGCAGCUUU	17	2148
  BCL11A-1664	+	GAAGGGGCUCAGCGAGC	17	2149
  BCL11A-1665	+	AGAAGGGGCUCAGCGAG	17	2150
  BCL11A-1666	+	CUUAGAGAAGGGGCUCA	17	2151
  BCL11A-1667	+	CUUGAUGCGCUUAGAGA	17	2152
  BCL11A-1668	+	GCUUGAUGCGCUUAGAG	17	2153
  BCL11A-1669	+	CGAGCUUGAUGCGCUUA	17	2154
  BCL11A-1670	+	CUCGAGCUUGAUGCGCU	17	2155
  BCL11A-1671	+	GCAGGUCGAACUCCUUC	17	2156
  BCL11A-1672	+	UCGCGGCCGGGGGCAGG	17	2157
  BCL11A-1673	+	UGUUGGGCAUCGCGGCC	17	2158
  BCL11A-1674	+	GUGUUGGGCAUCGCGGC	17	2159
  BCL11A-1675	+	CGUGUUGGGCAUCGCGG	17	2160
  BCL11A-1676	+	AGUACACGUUCUCCGUG	17	2161
  BCL11A-1677	+	GUAGCCGGCGAGCCACU	17	2162
  BCL11A-1678	+	UGGAGGCCGCGUAGCCG	17	2163
  BCL11A-1679	+	GGGAUCUUUGAGCUGCC	17	2164
  BCL11A-1680	+	AGGGAUCUUUGAGCUGC	17	2165
  BCL11A-1681	+	AGCUAAGGAAGGGAUCU	17	2166
  BCL11A-1682	+	GUCUCCGAAGCUAAGGA	17	2167
  BCL11A-1683	+	AGUCUCCGAAGCUAAGG	17	2168
  BCL11A-1684	+	UGGAGUCUCCGAAGCUA	17	2169
  BCL11A-1685	+	CUGGAGUCUCCGAAGCU	17	2170
  BCL11A-1686	+	GCGAUUGUCUGGAGUCU	17	2171
  BCL11A-1687	+	GGCAAAAGGCGAUUGUC	17	2172
  BCL11A-1688	+	AGGCAAAAGGCGAUUGU	17	2173
  BCL11A-1689	+	CGAGGAGUGCUCCGACG	17	2174
  BCL11A-1690	+	CCGAGGAGUGCUCCGAC	17	2175
  BCL11A-1691	+	CUCCGAGGAGUGCUCCG	17	2176
  BCL11A-1692	+	CAAACUCCCGUUCUCCG	17	2177
  BCL11A-1693	+	GCAAACUCCCGUUCUCC	17	2178
  BCL11A-1694	+	GCGCAAACUCCCGUUCU	17	2179
  BCL11A-1695	+	GCUCCCCGGGCGGUGUG	17	2180
  BCL11A-1696	+	CAGCUCCCCGGGCGGUG	17	2181
  BCL11A-1697	+	CCAGCUCCCCGGGCGGU	17	2182
  BCL11A-1698	+	UCCCUCCGUCCAGCUCC	17	2183
  BCL11A-1699	+	UCCCGUGCCGCUGCGCC	17	2184
  BCL11A-1700	+	GGCCCGGACCACUAAUA	17	2185
  BCL11A-1701	+	GGGCCCGGACCACUAAU	17	2186
  BCL11A-1702	+	GCUGGGCCUGCCCGGGC	17	2187
  BCL11A-1703	+	UUUUGAGCUGGGCCUGC	17	2188
  BCL11A-1704	+	GUCUGCCCUCUUUUGAG	17	2189
  BCL11A-1705	+	GCUGCGUCUGCCCUCUU	17	2190
  BCL11A-1706	-	CCCCCAUUCGGCGUAGUACC	20	2191
  BCL11A-1707	-	CCCAUUCGGCGUAGUACCCA	20	2192
  BCL11A-1708	-	CUCAAGAUGUGUGGCAGUUU	20	2193
  BCL11A-1709	-	AGAUGUGUGGCAGUUUUCGG	20	2194
  BCL11A-1710	-	GAUGUGUGGCAGUUUUCGGA	20	2195
  BCL11A-1711	-	GGCAGUUUUCGGAUGGAAGC	20	2196
  BCL11A-1712	-	CAGUUUUCGGAUGGAAGCUC	20	2197
  BCL11A-1713	-	CCAUUCGGCGUAGUACC	17	2198
  BCL11A-1714	-	AUUCGGCGUAGUACCCA	17	2199
  BCL11A-1715	-	AAGAUGUGUGGCAGUUU	17	2200
  BCL11A-1716	-	UGUGUGGCAGUUUUCGG	17	2201
  BCL11A-1717	-	GUGUGGCAGUUUUCGGA	17	2202
  BCL11A-1718	-	AGUUUUCGGAUGGAAGC	17	2203
  BCL11A-1719	-	UUUUCGGAUGGAAGCUC	17	2204
  BCL11A-1720	+	ACGCCGAAUGGGGGUGUGUG	20	2205
  BCL11A-1721	+	ACUACGCCGAAUGGGGGUGU	20	2206
  BCL11A-1722	+	CUCUGGGUACUACGCCGAAU	20	2207
  BCL11A-1723	+	UCUCUGGGUACUACGCCGAA	20	2208
  BCL11A-1724	+	CUCUCUGGGUACUACGCCGA	20	2209
  BCL11A-1725	+	UGAGCUCUCUGGGUACUACG	20	2210
  BCL11A-1726	+	UGCCACACAUCUUGAGCUCU	20	2211
  BCL11A-1727	+	UCCGAAAACUGCCACACAUC	20	2212
  BCL11A-1728	+	AAGGGCUCUCGAGCUUCCAU	20	2213
  BCL11A-1729	+	CCGAAUGGGGGUGUGUG	17	2214
  BCL11A-1730	+	ACGCCGAAUGGGGGUGU	17	2215
  BCL11A-1731	+	UGGGUACUACGCCGAAU	17	2216
  BCL11A-1732	+	CUGGGUACUACGCCGAA	17	2217
  BCL11A-1733	+	UCUGGGUACUACGCCGA	17	2218
  BCL11A-1734	+	GCUCUCUGGGUACUACG	17	2219
  BCL11A-1735	+	CACACAUCUUGAGCUCU	17	2220
  BCL11A-1736	+	GAAAACUGCCACACAUC	17	2221
  BCL11A-1737	+	GGCUCUCGAGCUUCCAU	17	2222

• Table 2F provides exemplary targeting domains for knocking out the BCL11A 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-stranded 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 2F
  N. meningitidis gRNA targets
  for BCL11A knockout

  			Tar-
  			get
  gRNA	DNA	Targeting	Site
  Name	Strand	Domain	Length

  BCL11A-1738	−	AUCCAGGUCACGCCAGAGGA	20	2223
  BCL11A-1739	−	UGCAACACGCACAGAACACU	20	2224
  BCL11A-1740	−	UCCUUCCCAGCCACCUCUCC	20	2225
  BCL11A-1741	−	AUGGCUAUGGAGCCUCCCGC	20	2226
  BCL11A-1742	−	CAGGUCACGCCAGAGGA	17	2227
  BCL11A-1743	−	AACACGCACAGAACACU	17	2228
  BCL11A-1744	−	UUCCCAGCCACCUCUCC	17	2229
  BCL11A-1745	−	GCUAUGGAGCCUCCCGC	17	2230
  BCL11A-1746	+	UGAAAAAAGCAUCCAAUCCC	20	2231
  BCL11A-1747	+	GGAGGUUGGCAUCCAGGUCA	20	2232
  BCL11A-1748	+	CGCCUGGGAUGAGUGCAGAA	20	2233
  BCL11A-1749	+	UAGAAAGCGAACACGGAAGU	20	2234
  BCL11A-1750	+	GGCUAUGGAGCCUCCCGCCA	20	2235
  BCL11A-1751	+	CCUCCUCCCUCCCAGCCCCC	20	2236
  BCL11A-1752	+	CCCAUGACGGUCAAGUCCGA	20	2237
  BCL11A-1753	+	UUUGCCUCCUCGUCGGAGCA	20	2238
  BCL11A-1754	+	UGAAAAAAGCAUCCAAU	17	2239
  BCL11A-1755	+	GGAGGUUGGCAUCCAGG	17	2240
  BCL11A-1756	+	CGCCUGGGAUGAGUGCA	17	2241
  BCL11A-1757	+	UAGAAAGCGAACACGGA	17	2242
  BCL11A-1758	+	GGCUAUGGAGCCUCCCG	17	2243
  BCL11A-1759	+	CCUCCUCCCUCCCAGCC	17	2244
  BCL11A-1760	+	CCCAUGACGGUCAAGUC	17	2245
  BCL11A-1761	+	UUUGCCUCCUCGUCGGA	17	2246

• Table 3A provides exemplary targeting domains for repressing (i.e., knocking down or decreasing) expression of the BCL11A 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 a S. pyogenes eiCas9 molecule to cause a steric block at the promoter region 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 3A
  S. pyogenes gRNA targets for
  BCL11A knockdown

  			Target	SEQ
  	DNA		Site	ID
  gRNA Name	Strand	Targeting Domain	Length	NO

  BCL11A-1762	−	UCUUCUCCUUGCUGCCUCUG	20	2247
  BCL11A-1763	−	UCCUUGCUGCCUCUGAGGUU	20	2248
  BCL11A-1764	−	UGCUGCCUCUGAGGUUCGGU	20	2249
  BCL11A-1765	−	GCUGCCUCUGAGGUUCGGUC	20	2250
  BCL11A-1766	−	GCCUCUGAGGUUCGGUCGGG	20	2251
  BCL11A-1767	−	CCUCUGAGGUUCGGUCGGGA	20	2252
  BCL11A-1768	−	CUCUGAGGUUCGGUCGGGAG	20	2253
  BCL11A-1769	−	UGAGGUUCGGUCGGGAGGGG	20	2254
  BCL11A-1770	−	GAGGUUCGGUCGGGAGGGGA	20	2255
  BCL11A-1771	−	CGGUCGGGAGGGGAGGGCAG	20	2256
  BCL11A-1772	−	GGGGAGGGCAGCGGCAACCC	20	2257
  BCL11A-1773	−	GAGGGCAGCGGCAACCCAGG	20	2258
  BCL11A-1774	−	CAACCCAGGAGGCAGCAGUC	20	2259
  BCL11A-1775	−	AACCCAGGAGGCAGCAGUCC	20	2260
  BCL11A-1776	−	CUCCCUCUCCCGCGUGCCCC	20	2261
  BCL11A-1777	−	CCCCCGGCCGCCUCCUCCCC	20	2262
  BCL11A-1778	−	CGGCCCUAGCUCCUGCCCUU	20	2263
  BCL11A-1779	−	CCCUAGCUCCUGCCCUUCGG	20	2264
  BCL11A-1780	−	UAGCUCCUGCCCUUCGGCGG	20	2265
  BCL11A-1781	−	CUCCUGCCCUUCGGCGGCGG	20	2266
  BCL11A-1782	−	CUGCCCUUCGGCGGCGGCGG	20	2267
  BCL11A-1783	−	CCCUUCGGCGGCGGCGGCGG	20	2268
  BCL11A-1784	−	UUCGGCGGCGGCGGCGGCGG	20	2269
  BCL11A-1785	−	CGGCGGCGGCGGCGGCGGCG	20	2270
  BCL11A-1786	−	GGCGGCGGCGGCGGCGGCGC	20	2271
  BCL11A-1787	−	GGCGGCGGCGGCGGCGCGGG	20	2272
  BCL11A-1788	−	GCGGCGGCGGCGGCGCGGGA	20	2273
  BCL11A-1789	−	GGCGCGGGAGGGCAAGCGCG	20	2274
  BCL11A-1790	−	GGAGGGCAAGCGCGAGGAGC	20	2275
  BCL11A-1791	−	GCGCGAGGAGCCGGCACAAA	20	2276
  BCL11A-1792	−	GGAGCCGGCACAAAAGGCAG	20	2277
  BCL11A-1793	−	GAGCCGGCACAAAAGGCAGC	20	2278
  BCL11A-1794	−	GCGGGACAAACACCCACCUC	20	2279
  BCL11A-1795	−	GACAAACACCCACCUCUGGC	20	2280
  BCL11A-1796	−	CCACCUCUGGCCGGAACAAA	20	2281
  BCL11A-1797	−	CCUCUGGCCGGAACAAAAGG	20	2282
  BCL11A-1798	−	GGAACAAAAGGCGGCAGUGC	20	2283
  BCL11A-1799	−	GCCGCGUCUCCCGUCCUUCC	20	2284
  BCL11A-1800	−	UCCCGUCCUUCCCGGUCCCA	20	2285
  BCL11A-1801	−	CACGGCUCUCCCCGUCGCCG	20	2286
  BCL11A-1802	−	CGGCCCCUCUCCCGACUCCG	20	2287
  BCL11A-1803	−	UCUCCCGACUCCGCGGACUC	20	2288
  BCL11A-1804	−	CUCCGCGGACUCAGGAGCGC	20	2289
  BCL11A-1805	−	UCCGCGGACUCAGGAGCGCC	20	2290
  BCL11A-1806	−	CCGCGGACUCAGGAGCGCCG	20	2291
  BCL11A-1807	−	CGCGGACUCAGGAGCGCCGG	20	2292
  BCL11A-1808	−	GUGCCACUUUCUCACUAUUG	20	2293
  BCL11A-1809	−	UGCCACUUUCUCACUAUUGU	20	2294
  BCL11A-1810	−	GCCACUUUCUCACUAUUGUG	20	2295
  BCL11A-1811	−	ACACUUGACCGUGAGCGCGC	20	2296
  BCL11A-1812	−	AGUCUCACCUCUUUUCUCCC	20	2297
  BCL11A-1813	−	GUCUCACCUCUUUUCUCCCC	20	2298
  BCL11A-1814	−	CCUACCCCCCCAUUUUCUUA	20	2299
  BCL11A-1815	−	CCCCAUUUUCUUACGGUGAG	20	2300
  BCL11A-1816	−	CCCAUUUUCUUACGGUGAGU	20	2301
  BCL11A-1817	−	CCCCACCAGCUCCCACCCCC	20	2302
  BCL11A-1818	−	UGUUCAUUAUUUUGCAAAAC	20	2303
  BCL11A-1819	−	UCAUUAUUUUGCAAAACUGG	20	2304
  BCL11A-1820	−	CAUUAUUUUGCAAAACUGGC	20	2305
  BCL11A-1821	−	AUUAUUUUGCAAAACUGGCG	20	2306
  BCL11A-1822	−	AUUUUGCAAAACUGGCGGGG	20	2307
  BCL11A-1823	−	UUUUGCAAAACUGGCGGGGC	20	2308
  BCL11A-1824	−	UUUGCAAAACUGGCGGGGCG	20	2309
  BCL11A-1825	−	UUGCAAAACUGGCGGGGCGG	20	2310
  BCL11A-1826	−	UGCAAAACUGGCGGGGCGGG	20	2311
  BCL11A-1827	−	GCAAAACUGGCGGGGCGGGG	20	2312
  BCL11A-1828	−	CAAAACUGGCGGGGCGGGGG	20	2313
  BCL11A-1829	−	CUGGCGGGGCGGGGGGGGAG	20	2314
  BCL11A-1830	−	UUUCGAAAAGAGAAAUAAAG	20	2315
  BCL11A-1831	−	CGAAAAGAGAAAUAAAGCGG	20	2316
  BCL11A-1832	−	AGAGAAAUAAAGCGGCGGAA	20	2317
  BCL11A-1833	−	GAAAUAAAGCGGCGGAAAGG	20	2318
  BCL11A-1834	−	AGCGGCGGAAAGGAGGAAAG	20	2319
  BCL11A-1835	−	GGCGGAAAGGAGGAAAGAGG	20	2320
  BCL11A-1836	−	UAAAAUUAAAUAAAAUUAAA	20	2321
  BCL11A-1837	−	CUGUCUCAAAAGUGCAUACA	20	2322
  BCL11A-1838	−	CAAAAGUGCAUACACGGCAA	20	2323
  BCL11A-1839	−	UACACGGCAAUGGUUCCAGA	20	2324
  BCL11A-1840	−	ACACGGCAAUGGUUCCAGAU	20	2325
  BCL11A-1841	−	CAAUGGUUCCAGAUGGGAUG	20	2326
  BCL11A-1842	−	AAUGGUUCCAGAUGGGAUGA	20	2327
  BCL11A-1843	−	AUCUCUUUUACCUCGACUCU	20	2328
  BCL11A-1844	−	UCUUUUACCUCGACUCUCGG	20	2329
  BCL11A-1845	−	AUAAUUAUUAUUACUAUUAU	20	2330
  BCL11A-1846	−	UAAUUAUUAUUACUAUUAUU	20	2331
  BCL11A-1847	+	UAAUAAUCACGAGAGCGCGC	20	2332
  BCL11A-1848	+	CAGGACUAGAAGCAAAAGCG	20	2333
  BCL11A-1849	+	AGGACUAGAAGCAAAAGCGA	20	2334
  BCL11A-1850	+	GGACUAGAAGCAAAAGCGAG	20	2335
  BCL11A-1851	+	GACUAGAAGCAAAAGCGAGG	20	2336
  BCL11A-1852	+	AGCAAAAGCGAGGGGGAGAG	20	2337
  BCL11A-1853	+	GCAAAAGCGAGGGGGAGAGA	20	2338
  BCL11A-1854	+	CAAAAGCGAGGGGGAGAGAG	20	2339
  BCL11A-1855	+	AGAAAAACCUCCGAGAGUCG	20	2340
  BCL11A-1856	+	AGUCGAGGUAAAAGAGAUAA	20	2341
  BCL11A-1857	+	GUCGAGGUAAAAGAGAUAAA	20	2342
  BCL11A-1858	+	UCGAGGUAAAAGAGAUAAAG	20	2343
  BCL11A-1859	+	CGAGGUAAAAGAGAUAAAGG	20	2344
  BCL11A-1860	+	GAAAAAACCCUCAUCCCAUC	20	2345
  BCL11A-1861	+	CUUUAUUUCUCUUUUCGAAA	20	2346
  BCL11A-1862	+	CAAAAUAAUGAACAAUGCUA	20	2347
  BCL11A-1863	+	GAACAACUCACAUGCAAACC	20	2348
  BCL11A-1864	+	AACAACUCACAUGCAAACCU	20	2349
  BCL11A-1865	+	ACAACUCACAUGCAAACCUG	20	2350
  BCL11A-1866	+	CAACUCACAUGCAAACCUGG	20	2351
  BCL11A-1867	+	CUCACAUGCAAACCUGGGGG	20	2352
  BCL11A-1868	+	UCACAUGCAAACCUGGGGGU	20	2353
  BCL11A-1869	+	GCAAACCUGGGGGUGGGAGC	20	2354
  BCL11A-1870	+	AACCUGGGGGUGGGAGCUGG	20	2355
  BCL11A-1871	+	ACCUGGGGGUGGGAGCUGGU	20	2356
  BCL11A-1872	+	CCUGGGGGUGGGAGCUGGUG	20	2357
  BCL11A-1873	+	GGGUGGGAGCUGGUGGGGAA	20	2358
  BCL11A-1874	+	GGUGGGAGCUGGUGGGGAAA	20	2359
  BCL11A-1875	+	GGGAGCUGGUGGGGAAAGGG	20	2360
  BCL11A-1876	+	UCCCACUCACCGUAAGAAAA	20	2361
  BCL11A-1877	+	CCCACUCACCGUAAGAAAAU	20	2362
  BCL11A-1878	+	CCACUCACCGUAAGAAAAUG	20	2363
  BCL11A-1879	+	CACUCACCGUAAGAAAAUGG	20	2364
  BCL11A-1880	+	ACUCACCGUAAGAAAAUGGG	20	2365
  BCL11A-1881	+	CUCACCGUAAGAAAAUGGGG	20	2366
  BCL11A-1882	+	CCGUAAGAAAAUGGGGGGGU	20	2367
  BCL11A-1883	+	CGUAAGAAAAUGGGGGGGUA	20	2368
  BCL11A-1884	+	AAGAAAAUGGGGGGGUAGGG	20	2369
  BCL11A-1885	+	AGAAAAUGGGGGGGUAGGGA	20	2370
  BCL11A-1886	+	CAAGUCUAAAAAACGAUUCC	20	2371
  BCL11A-1887	+	AAGUCUAAAAAACGAUUCCC	20	2372
  BCL11A-1888	+	AGUCUAAAAAACGAUUCCCG	20	2373
  BCL11A-1889	+	ACGAUUCCCGGGGAGAAAAG	20	2374
  BCL11A-1890	+	GGGGAGAAAAGAGGUGAGAC	20	2375
  BCL11A-1891	+	AAAGAGGUGAGACUGGCUUU	20	2376
  BCL11A-1892	+	UUUGGACACCAGCGCGCUCA	20	2377
  BCL11A-1893	+	GCUCACGGUCAAGUGUGCAG	20	2378
  BCL11A-1894	+	CUCACGGUCAAGUGUGCAGC	20	2379
  BCL11A-1895	+	ACGGUCAAGUGUGCAGCGGG	20	2380
  BCL11A-1896	+	UCCCCACAAUAGUGAGAAAG	20	2381
  BCL11A-1897	+	AUAGUGAGAAAGUGGCACUG	20	2382
  BCL11A-1898	+	GAGAAAGUGGCACUGUGGAA	20	2383
  BCL11A-1899	+	AGAAAGUGGCACUGUGGAAA	20	2384
  BCL11A-1900	+	GAAAGUGGCACUGUGGAAAG	20	2385
  BCL11A-1901	+	GCACUGUGGAAAGGGGCCCC	20	2386
  BCL11A-1902	+	CCCCGGCGCUCCUGAGUCCG	20	2387
  BCL11A-1903	+	CGCUCCUGAGUCCGCGGAGU	20	2388
  BCL11A-1904	+	GCUCCUGAGUCCGCGGAGUC	20	2389
  BCL11A-1905	+	UGAGUCCGCGGAGUCGGGAG	20	2390
  BCL11A-1906	+	GAGUCCGCGGAGUCGGGAGA	20	2391
  BCL11A-1907	+	AGUCCGCGGAGUCGGGAGAG	20	2392
  BCL11A-1908	+	CGGAGUCGGGAGAGGGGCCG	20	2393
  BCL11A-1909	+	CGGGAGAGGGGCCGCGGCGA	20	2394
  BCL11A-1910	+	GGGAGAGGGGCCGCGGCGAC	20	2395
  BCL11A-1911	+	GGAGAGGGGCCGCGGCGACG	20	2396
  BCL11A-1912	+	CGCGGCGACGGGGAGAGCCG	20	2397
  BCL11A-1913	+	GCGGCGACGGGGAGAGCCGU	20	2398
  BCL11A-1914	+	GACGGGGAGAGCCGUGGGAC	20	2399
  BCL11A-1915	+	ACGGGGAGAGCCGUGGGACC	20	2400
  BCL11A-1916	+	GGAGAGCCGUGGGACCGGGA	20	2401
  BCL11A-1917	+	AGCCGUGGGACCGGGAAGGA	20	2402
  BCL11A-1918	+	GCCGUGGGACCGGGAAGGAC	20	2403
  BCL11A-1919	+	ACCGGGAAGGACGGGAGACG	20	2404
  BCL11A-1920	+	GGAAGGACGGGAGACGCGGC	20	2405
  BCL11A-1921	+	GGCACUGCCGCCUUUUGUUC	20	2406
  BCL11A-1922	+	CCGCCUUUUGUUCCGGCCAG	20	2407
  BCL11A-1923	+	CCUUUUGUUCCGGCCAGAGG	20	2408
  BCL11A-1924	+	CUUUUGUUCCGGCCAGAGGU	20	2409
  BCL11A-1925	+	UGUCCCGCUGCCUUUUGUGC	20	2410
  BCL11A-1926	+	GCCGCCGCCGCCGCCGCCGA	20	2411
  BCL11A-1927	+	CCGCCGCCGCCGCCGCCGAA	20	2412
  BCL11A-1928	+	CGCCGCCGCCGCCGAAGGGC	20	2413
  BCL11A-1929	+	GCCGCCGAAGGGCAGGAGCU	20	2414
  BCL11A-1930	+	CCGCCGAAGGGCAGGAGCUA	20	2415
  BCL11A-1931	+	CGAAGGGCAGGAGCUAGGGC	20	2416
  BCL11A-1932	+	GAAGGGCAGGAGCUAGGGCC	20	2417
  BCL11A-1933	+	AAGGGCAGGAGCUAGGGCCG	20	2418
  BCL11A-1934	+	AGGGCAGGAGCUAGGGCCGG	20	2419
  BCL11A-1935	+	GCAGGAGCUAGGGCCGGGGG	20	2420
  BCL11A-1936	+	GGAGCUAGGGCCGGGGGAGG	20	2421
  BCL11A-1937	+	GCUAGGGCCGGGGGAGGAGG	20	2422
  BCL11A-1938	+	GGGCCGGGGGAGGAGGCGGC	20	2423
  BCL11A-1939	+	GGCCGGGGGAGGAGGCGGCC	20	2424
  BCL11A-1940	+	GCCGGGGGAGGAGGCGGCCG	20	2425
  BCL11A-1941	+	CCGGGGGAGGAGGCGGCCGG	20	2426
  BCL11A-1942	+	AGGAGGCGGCCGGGGGCACG	20	2427
  BCL11A-1943	+	GGAGGCGGCCGGGGGCACGC	20	2428
  BCL11A-1944	+	CGGCCGGGGGCACGCGGGAG	20	2429
  BCL11A-1945	+	GGCCGGGGGCACGCGGGAGA	20	2430
  BCL11A-1946	+	CGGGGGCACGCGGGAGAGGG	20	2431
  BCL11A-1947	+	GGGGGCACGCGGGAGAGGGA	20	2432
  BCL11A-1948	+	GGCACGCGGGAGAGGGAGGG	20	2433
  BCL11A-1949	+	GCACGCGGGAGAGGGAGGGA	20	2434
  BCL11A-1950	+	GGAGAGGGAGGGAGGGAGCC	20	2435
  BCL11A-1951	+	GAGCCCGGACUGCUGCCUCC	20	2436
  BCL11A-1952	+	AGCCCGGACUGCUGCCUCCU	20	2437
  BCL11A-1953	+	CCCUCCCGACCGAACCUCAG	20	2438
  BCL11A-1954	+	ACCGAACCUCAGAGGCAGCA	20	2439
  BCL11A-1955	+	AGAGGCAGCAAGGAGAAGAC	20	2440
  BCL11A-1956	+	AAAAUAAAAUAAAUAAAACA	20	2441
  BCL11A-1957	−	UCUCCUUGCUGCCUCUG	17	2442
  BCL11A-1958	−	UUGCUGCCUCUGAGGUU	17	2443
  BCL11A-1959	−	UGCCUCUGAGGUUCGGU	17	2444
  BCL11A-1960	−	GCCUCUGAGGUUCGGUC	17	2445
  BCL11A-1961	−	UCUGAGGUUCGGUCGGG	17	2446
  BCL11A-1962	−	CUGAGGUUCGGUCGGGA	17	2447
  BCL11A-1963	−	UGAGGUUCGGUCGGGAG	17	2448
  BCL11A-1964	−	GGUUCGGUCGGGAGGGG	17	2449
  BCL11A-1965	−	GUUCGGUCGGGAGGGGA	17	2450
  BCL11A-1966	−	UCGGGAGGGGAGGGCAG	17	2451
  BCL11A-1967	−	GAGGGCAGCGGCAACCC	17	2452
  BCL11A-1968	−	GGCAGCGGCAACCCAGG	17	2453
  BCL11A-1969	−	CCCAGGAGGCAGCAGUC	17	2454
  BCL11A-1970	−	CCAGGAGGCAGCAGUCC	17	2455
  BCL11A-1971	−	CCUCUCCCGCGUGCCCC	17	2456
  BCL11A-1972	−	CCGGCCGCCUCCUCCCC	17	2457
  BCL11A-1973	−	CCCUAGCUCCUGCCCUU	17	2458
  BCL11A-1974	−	UAGCUCCUGCCCUUCGG	17	2459
  BCL11A-1975	−	CUCCUGCCCUUCGGCGG	17	2460
  BCL11A-1976	−	CUGCCCUUCGGCGGCGG	17	2461
  BCL11A-1977	−	CCCUUCGGCGGCGGCGG	17	2462
  BCL11A-1978	−	UUCGGCGGCGGCGGCGG	17	2463
  BCL11A-1979	−	GGCGGCGGCGGCGGCGG	17	2464
  BCL11A-1980	−	CGGCGGCGGCGGCGGCG	17	2465
  BCL11A-1981	−	GGCGGCGGCGGCGGCGG	17	2466
  BCL11A-1982	−	GGCGGCGGCGGCGCGGG	17	2467
  BCL11A-1983	−	GCGGCGGCGGCGCGGGA	17	2468
  BCL11A-1984	−	GCGGGAGGGCAAGCGCG	17	2469
  BCL11A-1985	−	GGGCAAGCGCGAGGAGC	17	2470
  BCL11A-1986	−	CGAGGAGCCGGCACAAA	17	2471
  BCL11A-1987	−	GCCGGCACAAAAGGCAG	17	2472
  BCL11A-1988	−	CCGGCACAAAAGGCAGC	17	2473
  BCL11A-1989	−	GGACAAACACCCACCUC	17	2474
  BCL11A-1990	−	AAACACCCACCUCUGGC	17	2475
  BCL11A-1991	−	CCUCUGGCCGGAACAAA	17	2476
  BCL11A-1992	−	CUGGCCGGAACAAAAGG	17	2477
  BCL11A-1993	−	ACAAAAGGCGGCAGUGC	17	2478
  BCL11A-1994	−	GCGUCUCCCGUCCUUCC	17	2479
  BCL11A-1995	−	CGUCCUUCCCGGUCCCA	17	2480
  BCL11A-1996	−	GGCUCUCCCCGUCGCCG	17	2481
  BCL11A-1997	−	CCCCUCUCCCGACUCCG	17	2482
  BCL11A-1998	−	CCCGACUCCGCGGACUC	17	2483
  BCL11A-1999	−	CGCGGACUCAGGAGCGC	17	2484
  BCL11A-2000	−	GCGGACUCAGGAGCGCC	17	2485
  BCL11A-2001	−	CGGACUCAGGAGCGCCG	17	2486
  BCL11A-2002	−	GGACUCAGGAGCGCCGG	17	2487
  BCL11A-2003	−	CCACUUUCUCACUAUUG	17	2488
  BCL11A-2004	−	CACUUUCUCACUAUUGU	17	2489
  BCL11A-2005	−	ACUUUCUCACUAUUGUG	17	2490
  BCL11A-2006	−	CUUGACCGUGAGCGCGC	17	2491
  BCL11A-2007	−	CUCACCUCUUUUCUCCC	17	2492
  BCL11A-2008	−	UCACCUCUUUUCUCCCC	17	2493
  BCL11A-2009	−	ACCCCCCCAUUUUCUUA	17	2494
  BCL11A-2010	−	CAUUUUCUUACGGUGAG	17	2495
  BCL11A-2011	−	AUUUUCUUACGGUGAGU	17	2496
  BCL11A-2012	−	CACCAGCUCCCACCCCC	17	2497
  BCL11A-2013	−	UCAUUAUUUUGCAAAAC	17	2498
  BCL11A-2014	−	UUAUUUUGCAAAACUGG	17	2499
  BCL11A-2015	−	UAUUUUGCAAAACUGGC	17	2500
  BCL11A-2016	−	AUUUUGCAAAACUGGCG	17	2501
  BCL11A-2017	−	UUGCAAAACUGGCGGGG	17	2502
  BCL11A-2018	−	UGCAAAACUGGCGGGGC	17	2503
  BCL11A-2019	−	GCAAAACUGGCGGGGCG	17	2504
  BCL11A-2020	−	CAAAACUGGCGGGGCGG	17	2505
  BCL11A-2021	−	AAAACUGGCGGGGCGGG	17	2506
  BCL11A-2022	−	AAACUGGCGGGGCGGGG	17	2507
  BCL11A-2023	−	AACUGGCGGGGCGGGGG	17	2508
  BCL11A-2024	−	GCGGGGCGGGGGGGGAG	17	2509
  BCL11A-2025	−	CGAAAAGAGAAAUAAAG	17	2510
  BCL11A-2026	−	AAAGAGAAAUAAAGCGG	17	2511
  BCL11A-2027	−	GAAAUAAAGCGGCGGAA	17	2512
  BCL11A-2028	−	AUAAAGCGGCGGAAAGG	17	2513
  BCL11A-2029	−	GGCGGAAAGGAGGAAAG	17	2514
  BCL11A-2030	−	GGAAAGGAGGAAAGAGG	17	2515
  BCL11A-2031	−	AAUUAAAUAAAAUUAAA	17	2516
  BCL11A-2032	−	UCUCAAAAGUGCAUACA	17	2517
  BCL11A-2033	−	AAGUGCAUACACGGCAA	17	2518
  BCL11A-2034	−	ACGGCAAUGGUUCCAGA	17	2519
  BCL11A-2035	−	CGGCAAUGGUUCCAGAU	17	2520
  BCL11A-2036	−	UGGUUCCAGAUGGGAUG	17	2521
  BCL11A-2037	−	GGUUCCAGAUGGGAUGA	17	2522
  BCL11A-2038	−	UCUUUUACCUCGACUCU	17	2523
  BCL11A-2039	−	UUUACCUCGACUCUCGG	17	2524
  BCL11A-2040	−	AUUAUUAUUACUAUUAU	17	2525
  BCL11A-2041	−	UUAUUAUUACUAUUAUU	17	2526
  BCL11A-2042	+	UAAUCACGAGAGCGCGC	17	2527
  BCL11A-2043	+	GACUAGAAGCAAAAGCG	17	2528
  BCL11A-2044	+	ACUAGAAGCAAAAGCGA	17	2529
  BCL11A-2045	+	CUAGAAGCAAAAGCGAG	17	2530
  BCL11A-2046	+	UAGAAGCAAAAGCGAGG	17	2531
  BCL11A-2047	+	AAAAGCGAGGGGGAGAG	17	2532
  BCL11A-2048	+	AAAGCGAGGGGGAGAGA	17	2533
  BCL11A-2049	+	AAGCGAGGGGGAGAGAG	17	2534
  BCL11A-2050	+	AAAACCUCCGAGAGUCG	17	2535
  BCL11A-2051	+	CGAGGUAAAAGAGAUAA	17	2536
  BCL11A-2052	+	GAGGUAAAAGAGAUAAA	17	2537
  BCL11A-2053	+	AGGUAAAAGAGAUAAAG	17	2538
  BCL11A-2054	+	GGUAAAAGAGAUAAAGG	17	2539
  BCL11A-2055	+	AAAACCCUCAUCCCAUC	17	2540
  BCL11A-2056	+	UAUUUCUCUUUUCGAAA	17	2541
  BCL11A-2057	+	AAUAAUGAACAAUGCUA	17	2542
  BCL11A-2058	+	CAACUCACAUGCAAACC	17	2543
  BCL11A-2059	+	AACUCACAUGCAAACCU	17	2544
  BCL11A-2060	+	ACUCACAUGCAAACCUG	17	2545
  BCL11A-2061	+	CUCACAUGCAAACCUGG	17	2546
  BCL11A-2062	+	ACAUGCAAACCUGGGGG	17	2547
  BCL11A-2063	+	CAUGCAAACCUGGGGGU	17	2548
  BCL11A-2064	+	AACCUGGGGGUGGGAGC	17	2549
  BCL11A-2065	+	CUGGGGGUGGGAGCUGG	17	2550
  BCL11A-2066	+	UGGGGGUGGGAGCUGGU	17	2551
  BCL11A-2067	+	GGGGGUGGGAGCUGGUG	17	2552
  BCL11A-2068	+	UGGGAGCUGGUGGGGAA	17	2553
  BCL11A-2069	+	GGGAGCUGGUGGGGAAA	17	2554
  BCL11A-2070	+	AGCUGGUGGGGAAAGGG	17	2555
  BCL11A-2071	+	CACUCACCGUAAGAAAA	17	2556
  BCL11A-2072	+	ACUCACCGUAAGAAAAU	17	2557
  BCL11A-2073	+	CUCACCGUAAGAAAAUG	17	2558
  BCL11A-2074	+	UCACCGUAAGAAAAUGG	17	2559
  BCL11A-2075	+	CACCGUAAGAAAAUGGG	17	2560
  BCL11A-2076	+	ACCGUAAGAAAAUGGGG	17	2561
  BCL11A-2077	+	UAAGAAAAUGGGGGGGU	17	2562
  BCL11A-2078	+	AAGAAAAUGGGGGGGUA	17	2563
  BCL11A-2079	+	AAAAUGGGGGGGUAGGG	17	2564
  BCL11A-2080	+	AAAUGGGGGGGUAGGGA	17	2565
  BCL11A-2081	+	GUCUAAAAAACGAUUCC	17	2566
  BCL11A-2082	+	UCUAAAAAACGAUUCCC	17	2567
  BCL11A-2083	+	CUAAAAAACGAUUCCCG	17	2568
  BCL11A-2084	+	AUUCCCGGGGAGAAAAG	17	2569
  BCL11A-2085	+	GAGAAAAGAGGUGAGAC	17	2570
  BCL11A-2086	+	GAGGUGAGACUGGCUUU	17	2571
  BCL11A-2087	+	GGACACCAGCGCGCUCA	17	2572
  BCL11A-2088	+	CACGGUCAAGUGUGCAG	17	2573
  BCL11A-2089	+	ACGGUCAAGUGUGCAGC	17	2574
  BCL11A-2090	+	GUCAAGUGUGCAGCGGG	17	2575
  BCL11A-2091	+	CCACAAUAGUGAGAAAG	17	2576
  BCL11A-2092	+	GUGAGAAAGUGGCACUG	17	2577
  BCL11A-2093	+	AAAGUGGCACUGUGGAA	17	2578
  BCL11A-2094	+	AAGUGGCACUGUGGAAA	17	2579
  BCL11A-2095	+	AGUGGCACUGUGGAAAG	17	2580
  BCL11A-2096	+	CUGUGGAAAGGGGCCCC	17	2581
  BCL11A-2097	+	CGGCGCUCCUGAGUCCG	17	2582
  BCL11A-2098	+	UCCUGAGUCCGCGGAGU	17	2583
  BCL11A-2099	+	CCUGAGUCCGCGGAGUC	17	2584
  BCL11A-2100	+	GUCCGCGGAGUCGGGAG	17	2585
  BCL11A-2101	+	UCCGCGGAGUCGGGAGA	17	2586
  BCL11A-2102	+	CCGCGGAGUCGGGAGAG	17	2587
  BCL11A-2103	+	AGUCGGGAGAGGGGCCG	17	2588
  BCL11A-2104	+	GAGAGGGGCCGCGGCGA	17	2589
  BCL11A-2105	+	AGAGGGGCCGCGGCGAC	17	2590
  BCL11A-2106	+	GAGGGGCCGCGGCGACG	17	2591
  BCL11A-2107	+	GGCGACGGGGAGAGCCG	17	2592
  BCL11A-2108	+	GCGACGGGGAGAGCCGU	17	2593
  BCL11A-2109	+	GGGGAGAGCCGUGGGAC	17	2594
  BCL11A-2110	+	GGGAGAGCCGUGGGACC	17	2595
  BCL11A-2111	+	GAGCCGUGGGACCGGGA	17	2596
  BCL11A-2112	+	CGUGGGACCGGGAAGGA	17	2597
  BCL11A-2113	+	GUGGGACCGGGAAGGAC	17	2598
  BCL11A-2114	+	GGGAAGGACGGGAGACG	17	2599
  BCL11A-2115	+	AGGACGGGAGACGCGGC	17	2600
  BCL11A-2116	+	ACUGCCGCCUUUUGUUC	17	2601
  BCL11A-2117	+	CCUUUUGUUCCGGCCAG	17	2602
  BCL11A-2118	+	UUUGUUCCGGCCAGAGG	17	2603
  BCL11A-2119	+	UUGUUCCGGCCAGAGGU	17	2604
  BCL11A-2120	+	CCCGCUGCCUUUUGUGC	17	2605
  BCL11A-2121	+	GCCGCCGCCGCCGCCGA	17	2606
  BCL11A-2122	+	CCGCCGCCGCCGCCGAA	17	2607
  BCL11A-2123	+	CGCCGCCGCCGAAGGGC	17	2608
  BCL11A-2124	+	GCCGAAGGGCAGGAGCU	17	2609
  BCL11A-2125	+	CCGAAGGGCAGGAGCUA	17	2610
  BCL11A-2126	+	AGGGCAGGAGCUAGGGC	17	2611
  BCL11A-2127	+	GGGCAGGAGCUAGGGCC	17	2612
  BCL11A-2128	+	GGCAGGAGCUAGGGCCG	17	2613
  BCL11A-2129	+	GCAGGAGCUAGGGCCGG	17	2614
  BCL11A-2130	+	GGAGCUAGGGCCGGGGG	17	2615
  BCL11A-2131	+	GCUAGGGCCGGGGGAGG	17	2616
  BCL11A-2132	+	AGGGCCGGGGGAGGAGG	17	2617
  BCL11A-2133	+	CCGGGGGAGGAGGCGGC	17	2618
  BCL11A-2134	+	CGGGGGAGGAGGCGGCC	17	2619
  BCL11A-2135	+	GGGGGAGGAGGCGGCCG	17	2620
  BCL11A-2136	+	GGGGAGGAGGCGGCCGG	17	2621
  BCL11A-2137	+	AGGCGGCCGGGGGCACG	17	2622
  BCL11A-2138	+	GGCGGCCGGGGGCACGC	17	2623
  BCL11A-2139	+	CCGGGGGCACGCGGGAG	17	2624
  BCL11A-2140	+	CGGGGGCACGCGGGAGA	17	2625
  BCL11A-2141	+	GGGCACGCGGGAGAGGG	17	2626
  BCL11A-2142	+	GGCACGCGGGAGAGGGA	17	2627
  BCL11A-2143	+	ACGCGGGAGAGGGAGGG	17	2628
  BCL11A-2144	+	CGCGGGAGAGGGAGGGA	17	2629
  BCL11A-2145	+	GAGGGAGGGAGGGAGCC	17	2630
  BCL11A-2146	+	CCCGGACUGCUGCCUCC	17	2631
  BCL11A-2147	+	CCGGACUGCUGCCUCCU	17	2632
  BCL11A-2148	+	UCCCGACCGAACCUCAG	17	2633
  BCL11A-2149	+	GAACCUCAGAGGCAGCA	17	2634
  BCL11A-2150	+	GGCAGCAAGGAGAAGAC	17	2635
  BCL11A-2151	+	AUAAAAUAAAUAAAACA	17	2636

• Table 3B provides exemplary targeting domains for repressing (i.e., knocking down or decreasing) expression of the BCL11A gene. Any of the targeting domains in the table can be used with a S. aureus eiCas9 molecule to cause a steric block in the promoter region to block transcription elongation resulting in the repression of the BCL6A gene. 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 3B
  S. aureus gRNA targets for BCL11A knockdown

  			Target	SEQ
  	DNA		Site	ID
  gRNA Name	Strand	Targeting Domain	Length	NO
  BCL11A-2152	−	CAGUCUUCUCCUUGCUGCCU	20	2637
  BCL11A-2153	−	UUGCUGCCUCUGAGGUUCGG	20	2638
  BCL11A-2154	−	UGCUGCCUCUGAGGUUCGGU	20	2639
  BCL11A-2155	−	GCUGCCUCUGAGGUUCGGUC	20	2640
  BCL11A-2156	−	UGCCUCUGAGGUUCGGUCGG	20	2641
  BCL11A-2157	−	GCCUCUGAGGUUCGGUCGGG	20	2642
  BCL11A-2158	−	CCUCUGAGGUUCGGUCGGGA	20	2643
  BCL11A-2159	−	CUCUGAGGUUCGGUCGGGAG	20	2644
  BCL11A-216O	−	CUGAGGUUCGGUCGGGAGGG	20	2645
  BCL11A-2161	−	AGGGGAGGGCAGCGGCAACC	20	2646
  BCL11A-2162	−	GGGGAGGGCAGCGGCAACCC	20	2647
  BCL11A-2163	−	GCAACCCAGGAGGCAGCAGU	20	2648
  BCL11A-2164	−	GCGGCGGCGGCGGCGGCGGC	20	2649
  BCL11A-2165	−	CGGCGGCGGCGGCGGCGGCG	20	2650
  BCL11A-2166	−	GGCGGCGGCGGCGGCGGCGC	20	2651
  BCL11A-2167	−	CGGCGGCGGCGGCGGCGCGG	20	2652
  BCL11A-2168	−	GGCGGCGCGGGAGGGCAAGC	20	2653
  BCL11A-2169	−	CGGCGCGGGAGGGCAAGCGC	20	2654
  BCL11A-2170	−	GGCGCGGGAGGGCAAGCGCG	20	2655
  BCL11A-2171	−	AGGAGCCGGCACAAAAGGCA	20	2656
  BCL11A-2172	−	GGAGCCGGCACAAAAGGCAG	20	2657
  BCL11A-2173	−	GGACAAACACCCACCUCUGG	20	2658
  BCL11A-2174	−	GACAAACACCCACCUCUGGC	20	2659
  BCL11A-2175	−	GCGGCCCCUCUCCCGACUCC	20	2660
  BCL11A-2176	−	CUCUCCCGACUCCGCGGACU	20	2661
  BCL11A-2177	−	UCUCCCGACUCCGCGGACUC	20	2662
  BCL11A-2178	−	ACUCCGCGGACUCAGGAGCG	20	2663
  BCL11A-2179	−	CUCCGCGGACUCAGGAGCGC	20	2664
  BCL11A-2180	−	UCCGCGGACUCAGGAGCGCC	20	2665
  BCL11A-2181	−	AGUGCCACUUUCUCACUAUU	20	2666
  BCL11A-2182	−	GUGCCACUUUCUCACUAUUG	20	2667
  BCL11A-2183	−	UGCCACUUUCUCACUAUUGU	20	2668
  BCL11A-2184	−	CUCCCGCUGCACACUUGACC	20	2669
  BCL11A-2185	−	CAGUCUCACCUCUUUUCUCC	20	2670
  BCL11A-2186	−	AGUCUCACCUCUUUUCUCCC	20	2671
  BCL11A-2187	−	GUCUCACCUCUUUUCUCCCC	20	2672
  BCL11A-2188	−	UACCCCCCCAUUUUCUUACG	20	2673
  BCL11A-2189	−	CCCCCAUUUUCUUACGGUGA	20	2674
  BCL11A-2190	−	CCCCAUUUUCUUACGGUGAG	20	2675
  BCL11A-2191	−	CCCAUUUUCUUACGGUGAGU	20	2676
  BCL11A-2192	−	UCCCACCCCCAGGUUUGCAU	20	2677
  BCL11A-2193	−	UUCAUUAUUUUGCAAAACUG	20	2678
  BCL11A-2194	−	UCAUUAUUUUGCAAAACUGG	20	2679
  BCL11A-2195	−	UAUUUUGCAAAACUGGCGGG	20	2680
  BCL11A-2196	−	AUUUUGCAAAACUGGCGGGG	20	2681
  BCL11A-2197	−	UUUUGCAAAACUGGCGGGGC	20	2682
  BCL11A-2198	−	UUUGCAAAACUGGCGGGGCG	20	2683
  BCL11A-2199	−	UUGCAAAACUGGCGGGGCGG	20	2684
  BCL11A-2200	−	UGCAAAACUGGCGGGGCGGG	20	2685
  BCL11A-2201	−	GCAAAACUGGCGGGGCGGGG	20	2686
  BCL11A-2202	−	CAAAACUGGCGGGGCGGGGG	20	2687
  BCL11A-2203	−	ACUGGCGGGGCGGGGGGGGA	20	2688
  BCL11A-2204	−	CUGGCGGGGCGGGGGGGGAG	20	2689
  BCL11A-2205	−	UGGAAUCAUUGCAUUCCUUU	20	2690
  BCL11A-2206	−	UCAUUGCAUUCCUUUUCGAA	20	2691
  BCL11A-2207	−	AUUGCAUUCCUUUUCGAAAA	20	2692
  BCL11A-2208	−	UCGAAAAGAGAAAUAAAGCG	20	2693
  BCL11A-2209	−	CGAAAAGAGAAAUAAAGCGG	20	2694
  BCL11A-2210	−	AAGAGAAAUAAAGCGGCGGA	20	2695
  BCL11A-2211	−	AGAGAAAUAAAGCGGCGGAA	20	2696
  BCL11A-2212	−	AGAAAUAAAGCGGCGGAAAG	20	2697
  BCL11A-2213	−	GAAAUAAAGCGGCGGAAAGG	20	2698
  BCL11A-2214	−	UAAAGCGGCGGAAAGGAGGA	20	2699
  BCL11A-2215	−	AAGCGGCGGAAAGGAGGAAA	20	2700
  BCL11A-2216	−	AGCGGCGGAAAGGAGGAAAG	20	2701
  BCL11A-2217	−	CGGCGGAAAGGAGGAAAGAG	20	2702
  BCL11A-2218	−	GGCGGAAAGGAGGAAAGAGG	20	2703
  BCL11A-2219	−	AUACACGGCAAUGGUUCCAG	20	2704
  BCL11A-2220	−	UACACGGCAAUGGUUCCAGA	20	2705
  BCL11A-2221	−	CGGCAAUGGUUCCAGAUGGG	20	2706
  BCL11A-2222	−	GCAAUGGUUCCAGAUGGGAU	20	2707
  BCL11A-2223	−	UAUCUCUUUUACCUCGACUC	20	2708
  BCL11A-2224	−	AUCUCUUUUACCUCGACUCU	20	2709
  BCL11A-2225	−	GACUCUCGGAGGUUUUUCUC	20	2710
  BCL11A-2226	−	AAUAAUUAUUAUUACUAUUA	20	2711
  BCL11A-2227	−	ACUAUUAUUGGGUUACUUAC	20	2712
  BCL11A-2228	−	UAUUAUUGGGUUACUUACGC	20	2713
  BCL11A-2229	−	UCUUCUCCUUGCUGCCU	17	2714
  BCL11A-2230	−	CUGCCUCUGAGGUUCGG	17	2715
  BCL11A-2231	−	UGCCUCUGAGGUUCGGU	17	2716
  BCL11A-2232	−	GCCUCUGAGGUUCGGUC	17	2717
  BCL11A-2233	−	CUCUGAGGUUCGGUCGG	17	2718
  BCL11A-2234	−	UCUGAGGUUCGGUCGGG	17	2719
  BCL11A-2235	−	CUGAGGUUCGGUCGGGA	17	2720
  BCL11A-2236	−	UGAGGUUCGGUCGGGAG	17	2721
  BCL11A-2237	−	AGGUUCGGUCGGGAGGG	17	2722
  BCL11A-2238	−	GGAGGGCAGCGGCAACC	17	2723
  BCL11A-2239	−	GAGGGCAGCGGCAACCC	17	2724
  BCL11A-2240	−	ACCCAGGAGGCAGCAGU	17	2725
  BCL11A-2241	−	GCGGCGGCGGCGGCGGC	17	2726
  BCL11A-2242	−	CGGCGGCGGCGGCGGCG	17	2727
  BCL11A-2243	−	GGCGGCGGCGGCGGCGC	17	2728
  BCL11A-2244	−	CGGCGGCGGCGGCGCGG	17	2729
  BCL11A-2245	−	GGCGCGGGAGGGCAAGC	17	2730
  BCL11A-2246	−	CGCGGGAGGGCAAGCGC	17	2731
  BCL11A-2247	−	GCGGGAGGGCAAGCGCG	17	2732
  BCL11A-2248	−	AGCCGGCACAAAAGGCA	17	2733
  BCL11A-2249	−	GCCGGCACAAAAGGCAG	17	2734
  BCL11A-2250	−	CAAACACCCACCUCUGG	17	2735
  BCL11A-2251	−	AAACACCCACCUCUGGC	17	2736
  BCL11A-2252	−	GCCCCUCUCCCGACUCC	17	2737
  BCL11A-2253	−	UCCCGACUCCGCGGACU	17	2738
  BCL11A-2254	−	CCCGACUCCGCGGACUC	17	2739
  BCL11A-2255	−	CCGCGGACUCAGGAGCG	17	2740
  BCL11A-2256	−	CGCGGACUCAGGAGCGC	17	2741
  BCL11A-2257	−	GCGGACUCAGGAGCGCC	17	2742
  BCL11A-2258	−	GCCACUUUCUCACUAUU	17	2743
  BCL11A-2259	−	CCACUUUCUCACUAUUG	17	2744
  BCL11A-2260	−	CACUUUCUCACUAUUGU	17	2745
  BCL11A-2261	−	CCGCUGCACACUUGACC	17	2746
  BCL11A-2262	−	UCUCACCUCUUUUCUCC	17	2747
  BCL11A-2263	−	CUCACCUCUUUUCUCCC	17	2748
  BCL11A-2264	−	UCACCUCUUUUCUCCCC	17	2749
  BCL11A-2265	−	CCCCCCAUUUUCUUACG	17	2750
  BCL11A-2266	−	CCAUUUUCUUACGGUGA	17	2751
  BCL11A-2267	−	CAUUUUCUUACGGUGAG	17	2752
  BCL11A-2268	−	AUUUUCUUACGGUGAGU	17	2753
  BCL11A-2269	−	CACCCCCAGGUUUGCAU	17	2754
  BCL11A-2270	−	AUUAUUUUGCAAAACUG	17	2755
  BCL11A-2271	−	UUAUUUUGCAAAACUGG	17	2756
  BCL11A-2272	−	UUUGCAAAACUGGCGGG	17	2757
  BCL11A-2273	−	UUGCAAAACUGGCGGGG	17	2758
  BCL11A-2274	−	UGCAAAACUGGCGGGGC	17	2759
  BCL11A-2275	−	GCAAAACUGGCGGGGCG	17	2760
  BCL11A-2276	−	CAAAACUGGCGGGGCGG	17	2761
  BCL11A-2277	−	AAAACUGGCGGGGCGGG	17	2762
  BCL11A-2278	−	AAACUGGCGGGGCGGGG	17	2763
  BCL11A-2279	−	AACUGGCGGGGCGGGGG	17	2764
  BCL11A-2280	−	GGCGGGGCGGGGGGGGA	17	2765
  BCL11A-2281	−	GCGGGGCGGGGGGGGAG	17	2766
  BCL11A-2282	−	AAUCAUUGCAUUCCUUU	17	2767
  BCL11A-2283	−	UUGCAUUCCUUUUCGAA	17	2768
  BCL11A-2284	−	GCAUUCCUUUUCGAAAA	17	2769
  BCL11A-2285	−	AAAAGAGAAAUAAAGCG	17	2770
  BCL11A-2286	−	AAAGAGAAAUAAAGCGG	17	2771
  BCL11A-2287	−	AGAAAUAAAGCGGCGGA	17	2772
  BCL11A-2288	−	GAAAUAAAGCGGCGGAA	17	2773
  BCL11A-2289	−	AAUAAAGCGGCGGAAAG	17	2774
  BCL11A-2290	−	AUAAAGCGGCGGAAAGG	17	2775
  BCL11A-2291	−	AGCGGCGGAAAGGAGGA	17	2776
  BCL11A-2292	−	CGGCGGAAAGGAGGAAA	17	2777
  BCL11A-2293	−	GGCGGAAAGGAGGAAAG	17	2778
  BCL11A-2294	−	CGGAAAGGAGGAAAGAG	17	2779
  BCL11A-2295	−	GGAAAGGAGGAAAGAGG	17	2780
  BCL11A-2296	−	CACGGCAAUGGUUCCAG	17	2781
  BCL11A-2297	−	ACGGCAAUGGUUCCAGA	17	2782
  BCL11A-2298	−	CAAUGGUUCCAGAUGGG	17	2783
  BCL11A-2299	−	AUGGUUCCAGAUGGGAU	17	2784
  BCL11A-2300	−	CUCUUUUACCUCGACUC	17	2785
  BCL11A-2301	−	UCUUUUACCUCGACUCU	17	2786
  BCL11A-2302	−	UCUCGGAGGUUUUUCUC	17	2787
  BCL11A-2303	−	AAUUAUUAUUACUAUUA	17	2788
  BCL11A-2304	−	AUUAUUGGGUUACUUAC	17	2789
  BCL11A-2305	−	UAUUGGGUUACUUACGC	17	2790
  BCL11A-2306	+	CGAACCUCAGAGGCAGCAAG	20	2791
  BCL11A-2307	+	ACCGAACCUCAGAGGCAGCA	20	2792
  BCL11A-2308	+	GACCGAACCUCAGAGGCAGC	20	2793
  BCL11A-2309	+	CUCCCCUCCCGACCGAACCU	20	2794
  BCL11A-2310	+	CCGCUGCCCUCCCCUCCCGA	20	2795
  BCL11A-2311	+	GGAGCCCGGACUGCUGCCUC	20	2796
  BCL11A-2312	+	GGGAGAGGGAGGGAGGGAGC	20	2797
  BCL11A-2313	+	GCACGCGGGAGAGGGAGGGA	20	2798
  BCL11A-2314	+	GGCACGCGGGAGAGGGAGGG	20	2799
  BCL11A-2315	+	GGGCACGCGGGAGAGGGAGG	20	2800
  BCL11A-2316	+	GGGGGCACGCGGGAGAGGGA	20	2801
  BCL11A-2317	+	CGGGGGCACGCGGGAGAGGG	20	2802
  BCL11A-2318	+	CCGGGGGCACGCGGGAGAGG	20	2803
  BCL11A-2319	+	GGCCGGGGGCACGCGGGAGA	20	2804
  BCL11A-2320	+	CGGCCGGGGGCACGCGGGAG	20	2805
  BCL11A-2321	+	GCGGCCGGGGGCACGCGGGA	20	2806
  BCL11A-2322	+	AGGCGGCCGGGGGCACGCGG	20	2807
  BCL11A-2323	+	GGAGGCGGCCGGGGGCACGC	20	2808
  BCL11A-2324	+	AGGAGGCGGCCGGGGGCACG	20	2809
  BCL11A-2325	+	GAGGAGGCGGCCGGGGGCAC	20	2810
  BCL11A-2326	+	GGCCGGGGGAGGAGGCGGCC	20	2811
  BCL11A-2327	+	GGGCCGGGGGAGGAGGCGGC	20	2812
  BCL11A-2328	+	AGGGCCGGGGGAGGAGGCGG	20	2813
  BCL11A-2329	+	GCAGGAGCUAGGGCCGGGGG	20	2814
  BCL11A-2330	+	GGCAGGAGCUAGGGCCGGGG	20	2815
  BCL11A-2331	+	AGGGCAGGAGCUAGGGCCGG	20	2816
  BCL11A-2332	+	AAGGGCAGGAGCUAGGGCCG	20	2817
  BCL11A-2333	+	GAAGGGCAGGAGCUAGGGCC	20	2818
  BCL11A-2334	+	CGAAGGGCAGGAGCUAGGGC	20	2819
  BCL11A-2335	+	CCGAAGGGCAGGAGCUAGGG	20	2820
  BCL11A-2336	+	CGCCGCCGAAGGGCAGGAGC	20	2821
  BCL11A-2337	+	CGCCGCCGCCGCCGAAGGGC	20	2822
  BCL11A-2338	+	CCGCCGCCGCCGCCGAAGGG	20	2823
  BCL11A-2339	+	CGCCGCCGCCGCCGCCGCCG	20	2824
  BCL11A-2340	+	CGCCGCCGCCGCCGCCGCCG	20	2825
  BCL11A-2341	+	GCCUUUUGUUCCGGCCAGAG	20	2826
  BCL11A-2342	+	CUGCCGCCUUUUGUUCCGGC	20	2827
  BCL11A-2343	+	GCCGUGGGACCGGGAAGGAC	20	2828
  BCL11A-2344	+	AGCCGUGGGACCGGGAAGGA	20	2829
  BCL11A-2345	+	GAGCCGUGGGACCGGGAAGG	20	2830
  BCL11A-2346	+	GGGAGAGCCGUGGGACCGGG	20	2831
  BCL11A-2347	+	ACGGGGAGAGCCGUGGGACC	20	2832
  BCL11A-2348	+	GACGGGGAGAGCCGUGGGAC	20	2833
  BCL11A-2349	+	CGACGGGGAGAGCCGUGGGA	20	2834
  BCL11A-2350	+	CGCGGCGACGGGGAGAGCCG	20	2835
  BCL11A-2351	+	CCGCGGCGACGGGGAGAGCC	20	2836
  BCL11A-2352	+	AGAGGGGCCGCGGCGACGGG	20	2837
  BCL11A-2353	+	GGAGAGGGGCCGCGGCGACG	20	2838
  BCL11A-2354	+	GGGAGAGGGGCCGCGGCGAC	20	2839
  BCL11A-2355	+	CGGGAGAGGGGCCGCGGCGA	20	2840
  BCL11A-2356	+	UCGGGAGAGGGGCCGCGGCG	20	2841
  BCL11A-2357	+	UGAGUCCGCGGAGUCGGGAG	20	2842
  BCL11A-2358	+	CUGAGUCCGCGGAGUCGGGA	20	2843
  BCL11A-2359	+	UCCUGAGUCCGCGGAGUCGG	20	2844
  BCL11A-2360	+	GCUCCUGAGUCCGCGGAGUC	20	2845
  BCL11A-2361	+	CGCUCCUGAGUCCGCGGAGU	20	2846
  BCL11A-2362	+	GCGCUCCUGAGUCCGCGGAG	20	2847
  BCL11A-2363	+	CCCCGGCGCUCCUGAGUCCG	20	2848
  BCL11A-2364	+	CCCCCGGCGCUCCUGAGUCC	20	2849
  BCL11A-2365	+	GAAAGGGGCCCCCGGCGCUC	20	2850
  BCL11A-2366	+	GAGAAAGUGGCACUGUGGAA	20	2851
  BCL11A-2367	+	UGAGAAAGUGGCACUGUGGA	20	2852
  BCL11A-2368	+	AUAGUGAGAAAGUGGCACUG	20	2853
  BCL11A-2369	+	AAUAGUGAGAAAGUGGCACU	20	2854
  BCL11A-2370	+	GUAGUCAUCCCCACAAUAGU	20	2855
  BCL11A-2371	+	AAGUAGUCAUCCCCACAAUA	20	2856
  BCL11A-2372	+	ACGGUCAAGUGUGCAGCGGG	20	2857
  BCL11A-2373	+	CACGGUCAAGUGUGCAGCGG	20	2858
  BCL11A-2374	+	CUCACGGUCAAGUGUGCAGC	20	2859
  BCL11A-2375	+	GCUCACGGUCAAGUGUGCAG	20	2860
  BCL11A-2376	+	CGCUCACGGUCAAGUGUGCA	20	2861
  BCL11A-2377	+	AAAAGAGGUGAGACUGGCUU	20	2862
  BCL11A-2378	+	GAUUCCCGGGGAGAAAAGAG	20	2863
  BCL11A-2379	+	AAAACGAUUCCCGGGGAGAA	20	2864
  BCL11A-2380	+	UCUAAAAAACGAUUCCCGGG	20	2865
  BCL11A-2381	+	AGUCUAAAAAACGAUUCCCG	20	2866
  BCL11A-2382	+	AAGUCUAAAAAACGAUUCCC	20	2867
  BCL11A-2383	+	CAAGUCUAAAAAACGAUUCC	20	2868
  BCL11A-2384	+	ACAAGUCUAAAAAACGAUUC	20	2869
  BCL11A-2385	+	AAUGGGGGGGUAGGGAGGGA	20	2870
  BCL11A-2386	+	AGAAAAUGGGGGGGUAGGGA	20	2871
  BCL11A-2387	+	AAGAAAAUGGGGGGGUAGGG	20	2872
  BCL11A-2388	+	UAAGAAAAUGGGGGGGUAGG	20	2873
  BCL11A-2389	+	CGUAAGAAAAUGGGGGGGUA	20	2874
  BCL11A-2390	+	CCGUAAGAAAAUGGGGGGGU	20	2875
  BCL11A-2391	+	ACCGUAAGAAAAUGGGGGGG	20	2876
  BCL11A-2392	+	CACUCACCGUAAGAAAAUGG	20	2877
  BCL11A-2393	+	CCACUCACCGUAAGAAAAUG	20	2878
  BCL11A-2394	+	CCCACUCACCGUAAGAAAAU	20	2879
  BCL11A-2395	+	UCCCACUCACCGUAAGAAAA	20	2880
  BCL11A-2396	+	UUCCCACUCACCGUAAGAAA	20	2881
  BCL11A-2397	+	GGUUGCUUCCCACUCACCGU	20	2882
  BCL11A-2398	+	GGUGGGAGCUGGUGGGGAAA	20	2883
  BCL11A-2399	+	GGGUGGGAGCUGGUGGGGAA	20	2884
  BCL11A-2400	+	GGGGUGGGAGCUGGUGGGGA	20	2885
  BCL11A-2401	+	CCUGGGGGUGGGAGCUGGUG	20	2886
  BCL11A-2402	+	ACCUGGGGGUGGGAGCUGGU	20	2887
  BCL11A-2403	+	AACCUGGGGGUGGGAGCUGG	20	2888
  BCL11A-2404	+	AAACCUGGGGGUGGGAGCUG	20	2889
  BCL11A-2405	+	UCACAUGCAAACCUGGGGGU	20	2890
  BCL11A-2406	+	CUCACAUGCAAACCUGGGGG	20	2891
  BCL11A-2407	+	ACUCACAUGCAAACCUGGGG	20	2892
  BCL11A-2408	+	AACAACUCACAUGCAAACCU	20	2893
  BCL11A-2409	+	GAACAACUCACAUGCAAACC	20	2894
  BCL11A-2410	+	CGAACAACUCACAUGCAAAC	20	2895
  BCL11A-2411	+	UAAUGAACAAUGCUAAGGUU	20	2896
  BCL11A-2412	+	CCCGCCAGUUUUGCAAAAUA	20	2897
  BCL11A-2413	+	CUUUAUUUCUCUUUUCGAAA	20	2898
  BCL11A-2414	+	GCUUUAUUUCUCUUUUCGAA	20	2899
  BCL11A-2415	+	CCGCCGCUUUAUUUCUCUUU	20	2900
  BCL11A-2416	+	CCAUUGCCGUGUAUGCACUU	20	2901
  BCL11A-2417	+	GAAAAAACCCUCAUCCCAUC	20	2902
  BCL11A-2418	+	GGAAAAAACCCUCAUCCCAU	20	2903
  BCL11A-2419	+	CGAGGUAAAAGAGAUAAAGG	20	2904
  BCL11A-2420	+	UCGAGGUAAAAGAGAUAAAG	20	2905
  BCL11A-2421	+	GUCGAGGUAAAAGAGAUAAA	20	2906
  BCL11A-2422	+	AGUCGAGGUAAAAGAGAUAA	20	2907
  BCL11A-2423	+	GAGUCGAGGUAAAAGAGAUA	20	2908
  BCL11A-2424	+	ACCUCCGAGAGUCGAGGUAA	20	2909
  BCL11A-2425	+	ACGAGAAAAACCUCCGAGAG	20	2910
  BCL11A-2426	+	UUUUCACGAGAAAAACCUCC	20	2911
  BCL11A-2427	+	AUUUUUCACGAGAAAAACCU	20	2912
  BCL11A-2428	+	UGCAUUUUUAAAUUUUUCAC	20	2913
  BCL11A-2429	+	CAUGCAUUUUUAAAUUUUUC	20	2914
  BCL11A-2430	+	AGCAAAAGCGAGGGGGAGAG	20	2915
  BCL11A-2431	+	AAGCAAAAGCGAGGGGGAGA	20	2916
  BCL11A-2432	+	AGAAGCAAAAGCGAGGGGGA	20	2917
  BCL11A-2433	+	CUAGAAGCAAAAGCGAGGGG	20	2918
  BCL11A-2434	+	GACUAGAAGCAAAAGCGAGG	20	2919
  BCL11A-2435	+	GGACUAGAAGCAAAAGCGAG	20	2920
  BCL11A-2436	+	AGGACUAGAAGCAAAAGCGA	20	2921
  BCL11A-2437	+	CAGGACUAGAAGCAAAAGCG	20	2922
  BCL11A-2438	+	GCAGGACUAGAAGCAAAAGC	20	2923
  BCL11A-2439	+	GCGCAGGACUAGAAGCAAAA	20	2924
  BCL11A-2440	+	AUCACGAGAGCGCGCAGGAC	20	2925
  BCL11A-2441	+	UUAAUAAUCACGAGAGCGCG	20	2926
  BCL11A-2442	+	UAAUAAUUAUUAAUAAUCAC	20	2927
  BCL11A-2443	+	AAUAAUAAUUAUUAAUAAUC	20	2928
  BCL11A-2444	+	ACCUCAGAGGCAGCAAG	17	2929
  BCL11A-2445	+	GAACCUCAGAGGCAGCA	17	2930
  BCL11A-2446	+	CGAACCUCAGAGGCAGC	17	2931
  BCL11A-2447	+	CCCUCCCGACCGAACCU	17	2932
  BCL11A-2448	+	CUGCCCUCCCCUCCCGA	17	2933
  BCL11A-2449	+	GCCCGGACUGCUGCCUC	17	2934
  BCL11A-2450	+	AGAGGGAGGGAGGGAGC	17	2935
  BCL11A-2451	+	CGCGGGAGAGGGAGGGA	17	2936
  BCL11A-2452	+	ACGCGGGAGAGGGAGGG	17	2937
  BCL11A-2453	+	CACGCGGGAGAGGGAGG	17	2938
  BCL11A-2454	+	GGCACGCGGGAGAGGGA	17	2939
  BCL11A-2455	+	GGGCACGCGGGAGAGGG	17	2940
  BCL11A-2456	+	GGGGCACGCGGGAGAGG	17	2941
  BCL11A-2457	+	CGGGGGCACGCGGGAGA	17	2942
  BCL11A-2458	+	CCGGGGGCACGCGGGAG	17	2943
  BCL11A-2459	+	GCCGGGGGCACGCGGGA	17	2944
  BCL11A-2460	+	CGGCCGGGGGCACGCGG	17	2945
  BCL11A-2461	+	GGCGGCCGGGGGCACGC	17	2946
  BCL11A-2462	+	AGGCGGCCGGGGGCACG	17	2947
  BCL11A-2463	+	GAGGCGGCCGGGGGCAC	17	2948
  BCL11A-2464	+	CGGGGGAGGAGGCGGCC	17	2949
  BCL11A-2465	+	CCGGGGGAGGAGGCGGC	17	2950
  BCL11A-2466	+	GCCGGGGGAGGAGGCGG	17	2951
  BCL11A-2467	+	GGAGCUAGGGCCGGGGG	17	2952
  BCL11A-2468	+	AGGAGCUAGGGCCGGGG	17	2953
  BCL11A-2469	+	GCAGGAGCUAGGGCCGG	17	2954
  BCL11A-2470	+	GGCAGGAGCUAGGGCCG	17	2955
  BCL11A-2471	+	GGGCAGGAGCUAGGGCC	17	2956
  BCL11A-2472	+	AGGGCAGGAGCUAGGGC	17	2957
  BCL11A-2473	+	AAGGGCAGGAGCUAGGG	17	2958
  BCL11A-2474	+	CGCCGAAGGGCAGGAGC	17	2959
  BCL11A-2475	+	CGCCGCCGCCGAAGGGC	17	2960
  BCL11A-2476	+	CCGCCGCCGCCGAAGGG	17	2961
  BCL11A-2477	+	CGCCGCCGCCGCCGCCG	17	2962
  BCL11A-2478	+	CGCCGCCGCCGCCGCCG	17	2963
  BCL11A-2479	+	UUUUGUUCCGGCCAGAG	17	2964
  BCL11A-2480	+	CCGCCUUUUGUUCCGGC	17	2965
  BCL11A-2481	+	GUGGGACCGGGAAGGAC	17	2966
  BCL11A-2482	+	CGUGGGACCGGGAAGGA	17	2967
  BCL11A-2483	+	CCGUGGGACCGGGAAGG	17	2968
  BCL11A-2484	+	AGAGCCGUGGGACCGGG	17	2969
  BCL11A-2485	+	GGGAGAGCCGUGGGACC	17	2970
  BCL11A-2486	+	GGGGAGAGCCGUGGGAC	17	2971
  BCL11A-2487	+	CGGGGAGAGCCGUGGGA	17	2972
  BCL11A-2488	+	GGCGACGGGGAGAGCCG	17	2973
  BCL11A-2489	+	CGGCGACGGGGAGAGCC	17	2974
  BCL11A-2490	+	GGGGCCGCGGCGACGGG	17	2975
  BCL11A-2491	+	GAGGGGCCGCGGCGACG	17	2976
  BCL11A-2492	+	AGAGGGGCCGCGGCGAC	17	2977
  BCL11A-2493	+	GAGAGGGGCCGCGGCGA	17	2978
  BCL11A-2494	+	GGAGAGGGGCCGCGGCG	17	2979
  BCL11A-2495	+	GUCCGCGGAGUCGGGAG	17	2980
  BCL11A-2496	+	AGUCCGCGGAGUCGGGA	17	2981
  BCL11A-2497	+	UGAGUCCGCGGAGUCGG	17	2982
  BCL11A-2498	+	CCUGAGUCCGCGGAGUC	17	2983
  BCL11A-2499	+	UCCUGAGUCCGCGGAGU	17	2984
  BCL11A-2500	+	CUCCUGAGUCCGCGGAG	17	2985
  BCL11A-2501	+	CGGCGCUCCUGAGUCCG	17	2986
  BCL11A-2502	+	CCGGCGCUCCUGAGUCC	17	2987
  BCL11A-2503	+	AGGGGCCCCCGGCGCUC	17	2988
  BCL11A-2504	+	AAAGUGGCACUGUGGAA	17	2989
  BCL11A-2505	+	GAAAGUGGCACUGUGGA	17	2990
  BCL11A-2506	+	GUGAGAAAGUGGCACUG	17	2991
  BCL11A-2507	+	AGUGAGAAAGUGGCACU	17	2992
  BCL11A-2508	+	GUCAUCCCCACAAUAGU	17	2993
  BCL11A-2509	+	UAGUCAUCCCCACAAUA	17	2994
  BCL11A-2510	+	GUCAAGUGUGCAGCGGG	17	2995
  BCL11A-2511	+	GGUCAAGUGUGCAGCGG	17	2996
  BCL11A-2512	+	ACGGUCAAGUGUGCAGC	17	2997
  BCL11A-2513	+	CACGGUCAAGUGUGCAG	17	2998
  BCL11A-2514	+	UCACGGUCAAGUGUGCA	17	2999
  BCL11A-2515	+	AGAGGUGAGACUGGCUU	17	3000
  BCL11A-2516	+	UCCCGGGGAGAAAAGAG	17	3001
  BCL11A-2517	+	ACGAUUCCCGGGGAGAA	17	3002
  BCL11A-2518	+	AAAAAACGAUUCCCGGG	17	3003
  BCL11A-2519	+	CUAAAAAACGAUUCCCG	17	3004
  BCL11A-2520	+	UCUAAAAAACGAUUCCC	17	3005
  BCL11A-2521	+	GUCUAAAAAACGAUUCC	17	3006
  BCL11A-2522	+	AGUCUAAAAAACGAUUC	17	3007
  BCL11A-2523	+	GGGGGGGUAGGGAGGGA	17	3008
  BCL11A-2524	+	AAAUGGGGGGGUAGGGA	17	3009
  BCL11A-2525	+	AAAAUGGGGGGGUAGGG	17	3010
  BCL11A-2526	+	GAAAAUGGGGGGGUAGG	17	3011
  BCL11A-2527	+	AAGAAAAUGGGGGGGUA	17	3012
  BCL11A-2528	+	UAAGAAAAUGGGGGGGU	17	3013
  BCL11A-2529	+	GUAAGAAAAUGGGGGGG	17	3014
  BCL11A-2530	+	UCACCGUAAGAAAAUGG	17	3015
  BCL11A-2531	+	CUCACCGUAAGAAAAUG	17	3016
  BCL11A-2532	+	ACUCACCGUAAGAAAAU	17	3017
  BCL11A-2533	+	CACUCACCGUAAGAAAA	17	3018
  BCL11A-2534	+	CCACUCACCGUAAGAAA	17	3019
  BCL11A-2535	+	UGCUUCCCACUCACCGU	17	3020
  BCL11A-2536	+	GGGAGCUGGUGGGGAAA	17	3021
  BCL11A-2537	+	UGGGAGCUGGUGGGGAA	17	3022
  BCL11A-2538	+	GUGGGAGCUGGUGGGGA	17	3023
  BCL11A-2539	+	GGGGGUGGGAGCUGGUG	17	3024
  BCL11A-2540	+	UGGGGGUGGGAGCUGGU	17	3025
  BCL11A-2541	+	CUGGGGGUGGGAGCUGG	17	3026
  BCL11A-2542	+	CCUGGGGGUGGGAGCUG	17	3027
  BCL11A-2543	+	CAUGCAAACCUGGGGGU	17	3028
  BCL11A-2544	+	ACAUGCAAACCUGGGGG	17	3029
  BCL11A-2545	+	CACAUGCAAACCUGGGG	17	3030
  BCL11A-2546	+	AACUCACAUGCAAACCU	17	3031
  BCL11A-2547	+	CAACUCACAUGCAAACC	17	3032
  BCL11A-2548	+	ACAACUCACAUGCAAAC	17	3033
  BCL11A-2549	+	UGAACAAUGCUAAGGUU	17	3034
  BCL11A-2550	+	GCCAGUUUUGCAAAAUA	17	3035
  BCL11A-2551	+	UAUUUCUCUUUUCGAAA	17	3036
  BCL11A-2552	+	UUAUUUCUCUUUUCGAA	17	3037
  BCL11A-2553	+	CCGCUUUAUUUCUCUUU	17	3038
  BCL11A-2554	+	UUGCCGUGUAUGCACUU	17	3039
  BCL11A-2555	+	AAAACCCUCAUCCCAUC	17	3040
  BCL11A-2556	+	AAAAACCCUCAUCCCAU	17	3041
  BCL11A-2557	+	GGUAAAAGAGAUAAAGG	17	3042
  BCL11A-2558	+	AGGUAAAAGAGAUAAAG	17	3043
  BCL11A-2559	+	GAGGUAAAAGAGAUAAA	17	3044
  BCL11A-2560	+	CGAGGUAAAAGAGAUAA	17	3045
  BCL11A-2561	+	UCGAGGUAAAAGAGAUA	17	3046
  BCL11A-2562	+	UCCGAGAGUCGAGGUAA	17	3047
  BCL11A-2563	+	AGAAAAACCUCCGAGAG	17	3048
  BCL11A-2564	+	UCACGAGAAAAACCUCC	17	3049
  BCL11A-2565	+	UUUCACGAGAAAAACCU	17	3050
  BCL11A-2566	+	AUUUUUAAAUUUUUCAC	17	3051
  BCL11A-2567	+	GCAUUUUUAAAUUUUUC	17	3052
  BCL11A-2568	+	AAAAGCGAGGGGGAGAG	17	3053
  BCL11A-2569	+	CAAAAGCGAGGGGGAGA	17	3054
  BCL11A-2570	+	AGCAAAAGCGAGGGGGA	17	3055
  BCL11A-2571	+	GAAGCAAAAGCGAGGGG	17	3056
  BCL11A-2572	+	UAGAAGCAAAAGCGAGG	17	3057
  BCL11A-2573	+	CUAGAAGCAAAAGCGAG	17	3058
  BCL11A-2574	+	ACUAGAAGCAAAAGCGA	17	3059
  BCL11A-2575	+	GACUAGAAGCAAAAGCG	17	3060
  BCL11A-2576	+	GGACUAGAAGCAAAAGC	17	3061
  BCL11A-2577	+	CAGGACUAGAAGCAAAA	17	3062
  BCL11A-2578	+	ACGAGAGCGCGCAGGAC	17	3063
  BCL11A-2579	+	AUAAUCACGAGAGCGCG	17	3064
  BCL11A-2580	+	UAAUUAUUAAUAAUCAC	17	3065
  BCL11A-2581	+	AAUAAUUAUUAAUAAUC	17	3066

• Table 3C provides exemplary targeting domains for repressing (i.e., knocking down or decreasing) expression of the BCL11A gene. Any of the targeting domains in the table can be used with an N. meningitidis eiCas9 molecule to cause a steric block in the promoter region to block transcription elongation resulting in the repression of the BCL11A gene. Any of the targeting domains in the table can be used with an N. meningitidis eiCas9 fused to a transcriptional repressor to decrease transcription and therefore downregulate gene expression.

• TABLE 3C
  N. meningitidis gRNA targets for
  BCL11A knockdown

  				Target	SEQ
  		DNA	Targeting	Site	ID
  	gRNA Name	Strand	Domain	Length	NO
  	BCL11A-2582	−	GCUUCUAGUC	20	3067
  			CUGCGCGCUC
  	BCL11A-2583	−	UCUAGUCCUG	17	3068
  			CGCGCUC
  	BCL11A-2584	+	UUUAGACUUG	20	3069
  			UACUCACUCC
  	BCL11A-2585	+	CAUUCCUUUU	20	3070
  			CGAAAAGAGA
  	BCL11A-2586	+	UUUAGACUUG	17	3071
  			UACUCAC
  	BCL11A-2587	+	CAUUCCUUUU	17	3072
  			CGAAAAG

• 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 bind within first 500 bp 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 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. 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 0-50 bp. 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 BCL11A-2666, BCL11A-2596 and BCL11A-2664, BCL11A-2596 and BCL11A-2666, BCL11A-2603 and BCL11A-2664, of BCL11A-2603 and BCL11A-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 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. For example, gRNA pairs that target upstream (i.e., 5′) of the enhancer region in the BCL11A gene (e.g., 2607 and BCL11A-2593, BCL11A-2607 and BCL11A-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 BCL11A gene (e.g., BCL11A-2589 and BCL11A-2664, BCL11A-2589 and BCL11A-2666, BCL11A-2596 and BCL11A-2664, BCL11A-2596 and BCL11A-2666, BCL11A-2603 and BCL11A-2664, of BCL11A-2603 and BCL11A-2666).

• TABLE 4A
  				Target	SEQ
  	1st Tier	DNA	Targeting	Site	ID
  	gRNA Name	Strand	Domain	Length	NO

  	BCL11A-2588	+	GAGCUCCAUG	20	3073
  			UGCAGAACGA
  	BCL11A-2589	+	GAGCUCCCAA	17	3074
  			CGGGCCG
  	BCL11A-2590	−	GAGUGCAGAA	20	3075
  			UAUGCCCCGC
  	BCL11A-2591	+	GAUAAACAAU	20	3076
  			CGUCAUCCUC
  	BCL11A-2592	+	GAUGCCAACC	20	3077
  			UCCACGGGAU
  	BCL11A-2593	−	GCAGAAUAUG	17	3078
  			CCCCGCA
  	BCL11A-2594	−	GCAUCCAAUC	20	3079
  			CCGUGGAGGU
  	BCL11A-2595	+	GCCAACCUCC	17	3080
  			ACGGGAU
  	BCL11A-2596	+	GCUCCCAACG	20	3081
  			GGCCGUGGUC
  	BCL11A-2597	−	GGAGCUCUAA	20	3082
  			UCCCCACGCC

• 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 bind within first 500 bp 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.
• 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 0-50 bp.
• 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 4B
  				Target	SEQ
  	2nd Tier	DNA	Targeting	Site	ID
  	gRNA Name	Strand	Domain	Length	NO

  	BCL11A-2598	−	AGCAUCCAAU	17	3083
  			CCCGUGG
  	BCL11A-2599	−	AGUGCAGAAU	20	3084
  			AUGCCCCGCA
  	BCL11A-2600	−	AUGUCUCGCC	17	3085
  			GCAAGCA
  	BCL11A-2601	+	AUUCCCGUUU	20	3086
  			GCUUAAGUGC
  	BCL11A-2602	+	CAUCCUCUGG	17	3087
  			CGUGACC
  	BCL11A-2603	+	CCCAACGGGC	17	3088
  			CGUGGUC
  	BCL11A-2604	+	CCCCCAAUGG	20	3089
  			GAAGUUCAUC
  	BCL11A-2605	+	CCCGUUUGCU	17	3090
  			UAAGUGC
  	BCL11A-2606	+	CGUCAUCCUC	20	3091
  			UGGCGUGACC
  	BCL11A-2607	+	UCAUCUCGAU	17	3092
  			UGGUGAA
  	BCL11A-2608	−	UCCAAUCCCG	17	3093
  			UGGAGGU
  	BCL11A-2609	+	UCCCGUUUGC	20	3094
  			UUAAGUGCUG
  	BCL11A-2610	−	UGAACCAGAC	20	3095
  			CACGGCCCGU
  	BCL11A-2611	−	UGCAGAAUAU	17	3096
  			GCCCCGC
  	BCL11A-2612	−	UGGCAUCCAG	20	3097
  			GUCACGCCAG
  	BCL11A-2613	−	UUAUCAACGU	17	3098
  			CAUCUAG
  	BCL11A-2614	+	UUCAUCUCGA	17	3099
  			UUGGUGA

• 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 bind within first 500 bp 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 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. 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 0-50 bp.
• 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 4C
  3rd Tier

  			Target	SEQ
  	DNA		Site	ID
  gRNA Name	Strand	Targeting Domain	Length	NO
  BCL11A-2615	−	GAAAAAAGCAUCCAAUCCCG	20	3100
  BCL11A-2616	−	GAACCAGACCACGGCCCGUU	20	3101
  BCL11A-2617	+	GACCUGGAUGCCAACCUCCA	20	3102
  BCL11A-2618	−	GAGCUCUAAUCCCCACGCCU	20	3103
  BCL11A-2619	−	GAUCAUGACCUCCUCACCUG	20	3104
  BCL11A-2620	−	GAUGAACUUCCCAUUGG	17	3105
  BCL11A-2621	−	GAUGAUGAACCAGACCA	17	3106
  BCL11A-2622	+	GAUGCUUUUUUCAUCUCGAU	20	3107
  BCL11A-2623	+	GCACUCAUCCCAGGCGU	17	3108
  BCL11A-2624	+	GCAUAUUCUGCACUCAUCCC	20	3109
  BCL11A-2625	−	GCCAGAUGAACUUCCCAUUG	20	3110
  BCL11A-2626	−	GCCCGUUGGGAGCUCCAGAA	20	3111
  BCL11A-2627	+	GCUAUGUGUUCCUGUUU	17	3112
  BCL11A-2628	+	GCUCCAUGUGCAGAACG	17	3113
  BCL11A-2629	−	GCUCUAAUCCCCACGCC	17	3114
  BCL11A-2630	+	GCUGGGGUUUGCCUUGCUUG	20	3115
  BCL11A-2631	+	GCUUUUUUCAUCUCGAU	17	3116
  BCL11A-2632	+	GGCACUGCCCACAGGUG	17	3117
  BCL11A-2633	+	GGCACUGCCCACAGGUGAGG	20	3118
  BCL11A-2634	−	GGCCCGUUGGGAGCUCCAGA	20	3119
  BCL11A-2635	+	GGGGUUUGCCUUGCUUG	17	3120
  BCL11A-2636	+	GUAAGAAUGGCUUCAAG	17	3121
  BCL11A-2637	+	GUGCAGAACGAGGGGAGGAG	20	3122
  BCL11A-2638	−	GUGCCAGAUGAACUUCCCAU	20	3123
  BCL11A-2639	+	GUUCAUCUGGCACUGCCCAC	20	3124
  BCL11A-2640	−	GUUGGGAGCUCCAGAAG	17	3125

• Table 4D provides exemplary targeting domains for knocking out the BCL11A gene by targeting the early coding sequence the BCL11A gene selected according to forth tier parameters. The targeting domains bind within first 500 bp 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 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. 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 0-50 bp.
• 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 BCL0A gene and the second pair of gRNAs are used to target downstream (i.e., 3′) of the enhancer region in the BCL11A gene.

• TABLE 4D
  4th Tier

  			Target	SEQ
  	DNA		Site	ID
  gRNA Name	Strand	Targeting Domain	Length	NO
  BCL11A-2641	−	AAAAGCAUCCAAUCCCG	17	3126
  BCL11A-2642	−	AAAAGCAUCCAAUCCCGUGG	20	3127
  BCL11A-2643	+	AAAAUAAGAAUGUCCCCCAA	20	3128
  BCL11A-2644	+	AAACAAUCGUCAUCCUC	17	3129
  BCL11A-2645	−	AAACGGAAACAAUGCAA	17	3130
  BCL11A-2646	−	AAACUUCUGCACUGGAG	17	3131
  BCL11A-2647	+	AAAUAAGAAUGUCCCCCAAU	20	3132
  BCL11A-2648	−	AACCCCAGCACUUAAGCAAA	20	3133
  BCL11A-2649	+	AAGAAUGGCUUCAAGAGGCU	20	3134
  BCL11A-2650	+	AAUGGCUUCAAGAGGCU	17	3135
  BCL11A-2651	−	ACAGAUGAUGAACCAGACCA	20	3136
  BCL11A-2652	−	ACCAGACCACGGCCCGU	17	3137
  BCL11A-2653	−	ACCCCAGCACUUAAGCAAAC	20	3138
  BCL11A-2654	+	ACCUGGAUGCCAACCUCCAC	20	3139
  BCL11A-2655	+	ACUGCCCACAGGUGAGG	17	3140
  BCL11A-2656	+	AGAGCUCCAUGUGCAGAACG	20	3141
  BCL11A-2657	−	AGAUGAACUUCCCAUUG	17	3142
  BCL11A-2658	+	AGCUCCAUGUGCAGAACGAG	20	3143
  BCL11A-2659	−	AGGAAUUUGCCCCAAAC	17	3144
  BCL11A-2660	+	AGGAGGUCAUGAUCCCCUUC	20	3145
  BCL11A-2661	+	AGGUCAUGAUCCCCUUC	17	3146
  BCL11A-2662	−	AUAAACUUCUGCACUGG	17	3147
  BCL11A-2663	+	AUAAGAAUGUCCCCCAA	17	3148
  BCL11A-2664	−	AUCAUGACCUCCUCACCUGU	20	3149
  BCL11A-2665	+	AUCUCGAUUGGUGAAGGGGA	20	3150
  BCL11A-2666	−	AUGACCUCCUCACCUGU	17	3151
  BCL11A-2667	+	AUGUGCAGAACGAGGGG	17	3152
  BCL11A-2668	+	AUUGGUGAAGGGGAAGG	17	3153
  BCL11A-2669	−	CACAAACGGAAACAAUGCAA	20	3154
  BCL11A-2670	+	CACUCAUCCCAGGCGUG	17	3155
  BCL11A-2671	+	CAGAACGAGGGGAGGAG	17	3156
  BCL11A-2672	−	CAGAUGAACUUCCCAUU	17	3157
  BCL11A-2673	+	CAGCUUUUUCUAAGCAG	17	3158
  BCL11A-2674	−	CAUCCAGGUCACGCCAG	17	3159
  BCL11A-2675	+	CAUCUCGAUUGGUGAAG	17	3160
  BCL11A-2676	+	CAUCUGGCACUGCCCAC	17	3161
  BCL11A-2677	−	CAUGACCUCCUCACCUG	17	3162
  BCL11A-2678	+	CCAAUGGGAAGUUCAUC	17	3163
  BCL11A-2679	+	CCACAGCUUUUUCUAAGCAG	20	3164
  BCL11A-2680	−	CCAGACCACGGCCCGUU	17	3165
  BCL11A-2681	−	CCAGAUGAACUUCCCAU	17	3166
  BCL11A-2682	−	CCAGAUGAACUUCCCAUUGG	20	3167
  BCL11A-2683	−	CCAGCACUUAAGCAAAC	17	3168
  BCL11A-2684	−	CCCAGCACUUAAGCAAA	17	3169
  BCL11A-2685	+	CCCCUUCUGGAGCUCCCAAC	20	3170
  BCL11A-2686	−	CCCGUUGGGAGCUCCAGAAG	20	3171
  BCL11A-2687	−	CCGUUGGGAGCUCCAGA	17	3172
  BCL11A-2688	+	CCGUUUGCUUAAGUGCU	17	3173
  BCL11A-2689	−	CCUCUGCUUAGAAAAAGCUG	20	3174
  BCL11A-2690	+	CCUUCUGGAGCUCCCAA	17	3175
  BCL11A-2691	−	CGUGGAGGUUGGCAUCC	17	3176
  BCL11A-2692	−	CGUUGGGAGCUCCAGAA	17	3177
  BCL11A-2693	+	CGUUUGCUUAAGUGCUG	17	3178
  BCL11A-2694	+	CUAUGUGUUCCUGUUUG	17	3179
  BCL11A-2695	+	CUCCAUGUGCAGAACGA	17	3180
  BCL11A-2696	−	CUCUAAUCCCCACGCCU	17	3181
  BCL11A-2697	+	CUGCACUCAUCCCAGGCGUG	20	3182
  BCL11A-2698	+	CUGCUAUGUGUUCCUGUUUG	20	3183
  BCL11A-2699	−	CUGCUUAGAAAAAGCUG	17	3184
  BCL11A-2700	+	CUGGAGCUCCCAACGGGCCG	20	3185
  BCL11A-2701	+	CUGGAUGCCAACCUCCA	17	3186
  BCL11A-2702	+	CUUCUGGAGCUCCCAAC	17	3187
  BCL11A-2703	−	UAAACUUCUGCACUGGA	17	3188
  BCL11A-2704	+	UAAGAAUGUCCCCCAAU	17	3189
  BCL11A-2705	−	UAGAGGAAUUUGCCCCAAAC	20	3190
  BCL11A-2706	+	UAUUCUGCACUCAUCCC	17	3191
  BCL11A-2707	+	UCCAUGUGCAGAACGAG	17	3192
  BCL11A-2708	+	UCCAUGUGCAGAACGAGGGG	20	3193
  BCL11A-2709	−	UCCCCUCGUUCUGCACA	17	3194
  BCL11A-2710	+	UCCCCUUCUGGAGCUCCCAA	20	3195
  BCL11A-2711	−	UCCCGUGGAGGUUGGCAUCC	20	3196
  BCL11A-2712	−	UCCUCCCCUCGUUCUGCACA	20	3197
  BCL11A-2713	+	UCGAUUGGUGAAGGGGA	17	3198
  BCL11A-2714	+	UCGAUUGGUGAAGGGGAAGG	20	3199
  BCL11A-2715	+	UCUGCACUCAUCCCAGGCGU	20	3200
  BCL11A-2716	+	UCUGGCACUGCCCACAGGUG	20	3201
  BCL11A-2717	+	UCUGUAAGAAUGGCUUCAAG	20	3202
  BCL11A-2718	+	UGCACUCAUCCCAGGCG	17	3203
  BCL11A-2719	−	UGCCAGAUGAACUUCCCAUU	20	3204
  BCL11A-2720	+	UGCUAUGUGUUCCUGUU	17	3205
  BCL11A-2721	+	UGGAUGCCAACCUCCAC	17	3206
  BCL11A-2722	+	UGGUUCAUCAUCUGUAAGAA	20	3207
  BCL11A-2723	−	UGUUUAUCAACGUCAUCUAG	20	3208
  BCL11A-2724	−	UUAUUUUUAUCGAGCACAAA	20	3209
  BCL11A-2725	+	UUCAUCAUCUGUAAGAA	17	3210
  BCL11A-2726	+	UUCCCGUUUGCUUAAGUGCU	20	3211
  BCL11A-2727	+	UUCUGCACUCAUCCCAGGCG	20	3212
  BCL11A-2728	+	UUUCAUCUCGAUUGGUGAAG	20	3213
  BCL11A-2729	+	UUUUCAUCUCGAUUGGUGAA	20	3214
  BCL11A-2730	−	UUUUUAUCGAGCACAAA	17	3215
  BCL11A-2731	+	UUUUUCAUCUCGAUUGGUGA	20	3216

• 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 outside the first 500 bp 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 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. 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 0-50 bp.
• 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 BCL23A gene, e.g., the first pair of gRNAs are used to target upstream (i.e., 5′) of the enhancer region in the BCL3A gene and the second pair of gRNAs are used to target downstream (i.e., 3′) of the enhancer region in the BCL11A gene.

• TABLE 4E
  5th Tier

  			Target	SEQ
  	DNA		Site	ID
  gRNA Name	Strand	Targeting Domain	Length	NO
  BCL11A-2732	+	UAUGCGGUCCGACUCGC	17	3217
  BCL11A-2733	−	UCGGACCGCAUAGACGA	17	3218
  BCL11A-2734	+	UGGGUACUACGCCGAAU	17	3219
  BCL11A-2735	+	GGUACUACGCCGAAUGG	17	3220
  BCL11A-2736	−	UUGCGACGAAGACUCGG	17	3221
  BCL11A-2737	+	CUGGGUACUACGCCGAA	17	3222
  BCL11A-2738	+	GGGUACUACGCCGAAUG	17	3223
  BCL11A-2739	+	UCGGACUUGACCGUCAU	17	3224
  BCL11A-2740	+	AGGGAUACCAACCCGCG	17	3225
  BCL11A-2741	−	CGCGCUCAAGUCCGUGG	17	3226
  BCL11A-2742	+	CGAGGAGUGCUCCGACG	17	3227
  BCL11A-2743	+	GUCGGACUUGACCGUCA	17	3228
  BCL11A-2744	+	UGCACGCGUGGUCGCAC	17	3229
  BCL11A-2745	−	CAGCGCGCUCAAGUCCG	17	3230
  BCL11A-2746	+	UACCAACCCGCGGGGUC	17	3231
  BCL11A-2747	−	GUGGCUCGCCGGCUACG	17	3232
  BCL11A-2748	+	CGGACUUGACCGUCAUG	17	3233
  BCL11A-2749	−	CACCGCAUAGAGCGCCU	17	3234
  BCL11A-2750	−	GCGCAUCAAGCUCGAGA	17	3235
  BCL11A-2751	+	GGCCCGGACCACUAAUA	17	3236
  BCL11A-2752	+	GCCCGGACCACUAAUAU	17	3237
  BCL11A-2753	−	GCAUAAGCGCGGCCACC	17	3238
  BCL11A-2754	+	AGGCGCUCUAUGCGGUG	17	3239
  BCL11A-2755	−	ACGGUCAAGUCCGACGA	17	3240
  BCL11A-2756	+	CGAGGCCGACUCGCCCG	17	3241
  BCL11A-2757	−	ACCGCAUAGAGCGCCUG	17	3242
  BCL11A-2758	−	CGACCACGCGUGCACCC	17	3243
  BCL11A-2759	+	GUACACGUUCUCCGUGU	17	3244
  BCL11A-2760	−	CACUUGCGACGAAGACU	17	3245
  BCL11A-2761	−	CGGGUUGGUAUCCCUUC	17	3246
  BCL11A-2762	−	CUCGUCGGAGCACUCCU	17	3247
  BCL11A-2763	+	CCCGGACCACUAAUAUG	17	3248
  BCL11A-2764	+	UCGGUGGUGGACUAAAC	17	3249
  BCL11A-2765	+	CAGGCGCUCUAUGCGGU	17	3250
  BCL11A-2766	+	AAGGGAUACCAACCCGC	17	3251
  BCL11A-2767	+	GGCGCUCUAUGCGGUGG	17	3252
  BCL11A-2768	−	CCACCGCAUAGAGCGCC	17	3253
  BCL11A-2769	−	UACUCGCAGUGGCUCGC	17	3254
  BCL11A-2770	−	CGGGCGAGUCGGCCUCG	17	3255
  BCL11A-2771	+	UACACGUUCUCCGUGUU	17	3256
  BCL11A-2772	−	AGCACGCCCCAUAUUAG	17	3257
  BCL11A-2773	+	GAAGGGAUACCAACCCG	17	3258
  BCL11A-2774	+	UUGGGCAUCGCGGCCGG	17	3259
  BCL11A-2775	−	CCGGGCGAGUCGGCCUC	17	3260
  BCL11A-2776	+	GGUGGAGAGACCGUCGU	17	3261
  BCL11A-2777	+	GUUGGGCAUCGCGGCCG	17	3262
  BCL11A-2778	−	AGAACGUGUACUCGCAG	17	3263
  BCL11A-2779	+	ACCAACCCGCGGGGUCA	17	3264
  BCL11A-2780	−	CACGAGAACAGCUCGCG	17	3265
  BCL11A-2781	−	UAUUAGUGGUCCGGGCC	17	3266
  BCL11A-2782	+	CGUCGCAAGUGUCCCUG	17	3267
  BCL11A-2783	+	CCCGCGAGCUGUUCUCG	17	3268
  BCL11A-2784	+	UGCGCCGGUGCACCACC	17	3269
  BCL11A-2785	−	CUGCCCGACGUCAUGCA	17	3270
  BCL11A-2786	−	GACGAAGACUCGGUGGC	17	3271
  BCL11A-2787	−	CCUGCCCGACGUCAUGC	17	3272
  BCL11A-2788	+	AAGGGCGGCUUGCUACC	17	3273
  BCL11A-2789	−	GGGUGGACUACGGCUUC	17	3274
  BCL11A-2790	+	UCGCUGGUGCCGGGUUC	17	3275
  BCL11A-2791	−	GGCGAGAAGCAUAAGCG	17	3276
  BCL11A-2792	+	GGACUUGAGCGCGCUGC	17	3277
  BCL11A-2793	−	CUCGGUGGCCGGCGAGU	17	3278
  BCL11A-2794	+	CCCGAGGCCGACUCGCC	17	3279
  BCL11A-2795	−	CCCGGGCGAGUCGGCCU	17	3280
  BCL11A-2796	−	CCGCAUAGAGCGCCUGG	17	3281
  BCL11A-2797	+	UGUUGGGCAUCGCGGCC	17	3282
  BCL11A-2798	+	GUGUUGGGCAUCGCGGC	17	3283
  BCL11A-2799	+	UCUCUCGAUACUGAUCC	17	3284
  BCL11A-2800	−	ACCCGAGUGCCUUUGAC	17	3285
  BCL11A-2801	+	UCCGACGAGGAGGCAAA	17	3286
  BCL11A-2802	−	ACCCGGCACCAGCGACU	17	3287
  BCL11A-2803	+	CCCCGUUCUCCGGGAUC	17	3288
  BCL11A-2804	+	CCGAGGCCGACUCGCCC	17	3289
  BCL11A-2805	−	CCCCAUAUUAGUGGUCC	17	3290
  BCL11A-2806	+	GACUUGGACUUGACCGG	17	3291
  BCL11A-2807	−	GCCCCAUAUUAGUGGUC	17	3292
  BCL11A-2808	−	AGGGUGGACUACGGCUU	17	3293
  BCL11A-2809	−	CAAAUCGUCCCCCAUGA	17	3294
  BCL11A-2810	−	CGACGUCAUGCAGGGCA	17	3295
  BCL11A-2811	−	GGCCGCGAUGCCCAACA	17	3296
  BCL11A-2812	+	CCAGGCGCUCUAUGCGG	17	3297
  BCL11A-2813	−	CCUGAUCCCGGAGAACG	17	3298
  BCL11A-2814	+	CCAACCCGCGGGGUCAG	17	3299
  BCL11A-2815	−	GGCGAGUCGGCCUCGGG	17	3300
  BCL11A-2816	+	GGCAAAAGGCGAUUGUC	17	3301
  BCL11A-2817	+	UUUGGACAGGCCCCCCG	17	3302
  BCL11A-2818	+	GCGGCUUGCUACCUGGC	17	3303
  BCL11A-2819	+	GGACUUGACCGUCAUGG	17	3304
  BCL11A-2820	+	GGAGUGCUCCGACGAGG	17	3305
  BCL11A-2821	−	AUUAGUGGUCCGGGCCC	17	3306
  BCL11A-2822	−	CCACGAGAACAGCUCGC	17	3307
  BCL11A-2823	−	GUAUCGAGAGAGGCUUC	17	3308
  BCL11A-2824	+	CUCCGUGUUGGGCAUCG	17	3309
  BCL11A-2825	+	CAAACUCCCGUUCUCCG	17	3310
  BCL11A-2826	−	ACCUGAUCCCGGAGAAC	17	3311
  BCL11A-2827	−	GGCACUGUUAAUGGCCG	17	3312
  BCL11A-2828	+	UUCUCCGGGAUCAGGUU	17	3313
  BCL11A-2829	−	UAUGGAGCCUCCCGCCA	17	3314
  BCL11A-2830	+	CUUGAUGCGCUUAGAGA	17	3315
  BCL11A-2831	−	UAGCAAGCCGCCCUUCC	17	3316
  BCL11A-2832	−	CCGGCUACGCGGCCUCC	17	3317
  BCL11A-2833	+	UCCAAGUGAUGUCUCGG	17	3318
  BCL11A-2834	−	GAACAGCUCGCGGGGCG	17	3319
  BCL11A-2835	−	GCUGCGGUUGAAUCCAA	17	3320
  BCL11A-2836	+	UGACUUGGACUUGACCG	17	3321
  BCL11A-2837	−	CCCGGAGAACGGGGACG	17	3322
  BCL11A-2838	+	GUGGCGCUUCAGCUUGC	17	3323
  BCL11A-2839	+	GUUCUCCGGGAUCAGGU	17	3324
  BCL11A-2840	+	CAGUGCCAUCGUCUAUG	17	3325
  BCL11A-2841	+	UCUCCGGGAUCAGGUUG	17	3326
  BCL11A-2842	−	GACGAUGGCACUGUUAA	17	3327
  BCL11A-2843	−	CUGCUCCCCGGGCGAGU	17	3328
  BCL11A-2844	+	CGGUGGUGGACUAAACA	17	3329
  BCL11A-2845	−	CUCGCGGGGCGCGGUCG	17	3330
  BCL11A-2846	+	AUGCCCUGCAUGACGUC	17	3331
  BCL11A-2847	+	UGGACUUGACCGGGGGC	17	3332
  BCL11A-2848	−	ACCACCGAGACAUCACU	17	3333
  BCL11A-2849	−	GGAGUUCGACCUGCCCC	17	3334
  BCL11A-2850	+	CCUGCAUGACGUCGGGC	17	3335
  BCL11A-2851	+	CUGCAUGACGUCGGGCA	17	3336
  BCL11A-2852	−	AGGAUCAGUAUCGAGAG	17	3337
  BCL11A-2853	+	GGACUUGACCGGGGGCU	17	3338
  BCL11A-2854	+	AAAGGCACUCGGGUGAU	17	3339
  BCL11A-2855	−	UGGACGGAGGGAUCUCG	17	3340
  BCL11A-2856	+	CCCCCAGGCGCUCUAUG	17	3341
  BCL11A-2857	−	CCGCCAUGGAUUUCUCU	17	3342
  BCL11A-2858	−	GGCGCGGUCGUGGGCGU	17	3343
  BCL11A-2859	−	AACCUGAUCCCGGAGAA	17	3344
  BCL11A-2860	+	CAUGCCCUGCAUGACGU	17	3345
  BCL11A-2861	+	CGCUGGUGCCGGGUUCC	17	3346
  BCL11A-2862	+	CCUGGAGGCCGCGUAGC	17	3347
  BCL11A-2863	−	CCCCUGACCCCGCGGGU	17	3348
  BCL11A-2864	+	GCUUAUGCUUCUCGCCC	17	3349
  BCL11A-2865	−	AAGUCAUGCGAGUUCUG	17	3350
  BCL11A-2866	+	CACCAAGUCGCUGGUGC	17	3351
  BCL11A-2867	−	CCCGAGUGCCUUUGACA	17	3352
  BCL11A-2868	+	CAUGACUUGGACUUGAC	17	3353
  BCL11A-2869	−	CGACCCCAACCUGAUCC	17	3354
  BCL11A-2870	+	ACCAAGUCGCUGGUGCC	17	3355
  BCL11A-2871	+	AAGUGAUGUCUCGGUGG	17	3356
  BCL11A-2872	−	CUUCUCCACACCGCCCG	17	3357
  BCL11A-2873	+	UGGAGUCUCCGAAGCUA	17	3358
  BCL11A-2874	−	CGCUUCUCCACACCGCC	17	3359
  BCL11A-2875	+	GCUGGUGCCGGGUUCCG	17	3360
  BCL11A-2876	−	CGCAGCGGCACGGGAAG	17	3361
  BCL11A-2877	+	GCAUCGCGGCCGGGGGC	17	3362
  BCL11A-2878	−	GAGCACUCCUCGGAGAA	17	3363
  BCL11A-2879	+	GGGGGGCGUCGCCAGGA	17	3364
  BCL11A-2880	+	GAAAGCGCCCUUCUGCC	17	3365
  BCL11A-2881	−	CUGGACGGAGGGAUCUC	17	3366
  BCL11A-2882	−	CGGCUUCGGGCUGAGCC	17	3367
  BCL11A-2883	+	GGGGGCGUCGCCAGGAA	17	3368
  BCL11A-2884	+	UAACCUUUGCAUAGGGC	17	3369
  BCL11A-2885	−	GGGCGAGUCGGCCUCGG	17	3370
  BCL11A-2886	−	CACACCGCCCGGGGAGC	17	3371
  BCL11A-2887	−	GGGAUCUCGGGGCGCAG	17	3372
  BCL11A-2888	+	CUCGCUGAAGUGCUGCA	17	3373
  BCL11A-2889	−	UCGGGGCGCAGCGGCAC	17	3374
  BCL11A-2890	−	AAGUCCCCUGACCCCGC	17	3375
  BCL11A-2891	−	GCCUUUUGCCUCCUCGU	17	3376
  BCL11A-2892	−	CACCUGGCCGAGGCCGA	17	3377
  BCL11A-2893	−	GGUAUCCCUUCAGGACU	17	3378
  BCL11A-2894	+	GUGGUGGACUAAACAGG	17	3379
  BCL11A-2895	+	GCGAGCUGUUCUCGUGG	17	3380
  BCL11A-2896	−	AGCACUCCUCGGAGAAC	17	3381
  BCL11A-2897	−	CAUGCAGCACUUCAGCG	17	3382
  BCL11A-2898	+	UGGCCUGGGUGCACGCG	17	3383
  BCL11A-2899	−	AGCGAGAGGGUGGACUA	17	3384
  BCL11A-2900	+	GCACAGGUUGCACUUGU	17	3385
  BCL11A-2901	+	GAGAAAUCCAUGGCGGG	17	3386
  BCL11A-2902	+	GCAGAACUCGCAUGACU	17	3387
  BCL11A-2903	+	UCUCCGAAGCUAAGGAA	17	3388
  BCL11A-2904	+	UGACGUCGGGCAGGGCG	17	3389
  BCL11A-2905	+	GGGUCCAAGUGAUGUCU	17	3390
  BCL11A-2906	−	GCAACCUGGUGGUGCAC	17	3391
  BCL11A-2907	+	GGUGGCGCGCCGCCUCC	17	3392
  BCL11A-2908	+	GCUGCCCACCAAGUCGC	17	3393
  BCL11A-2909	+	GUUCUCGCUCUUGAACU	17	3394
  BCL11A-2910	+	CCGCAGCACCCUGUCAA	17	3395
  BCL11A-2911	−	GAAGUCCCCUGACCCCG	17	3396
  BCL11A-2912	−	GCGCGGCCACCUGGCCG	17	3397
  BCL11A-2913	+	GGCGUCGCCAGGAAGGG	17	3398
  BCL11A-2914	−	GUUGAAUCCAAUGGCUA	17	3399
  BCL11A-2915	−	CUCGGGGCGCAGCGGCA	17	3400
  BCL11A-2916	−	CCGAGGCCGAGGGCCAC	17	3401
  BCL11A-2917	+	CUAAACAGGGGGGGAGU	17	3402
  BCL11A-2918	−	GCGGCACGGGAAGUGGA	17	3403
  BCL11A-2919	+	CACAGGUUGCACUUGUA	17	3404
  BCL11A-2920	−	CAGCGAGGCCUUCCACC	17	3405
  BCL11A-2921	−	AACCUGCUAAGAAUACC	17	3406
  BCL11A-2922	+	AUCCUGGUAUUCUUAGC	17	3407
  BCL11A-2923	+	GGUGGUGGACUAAACAG	17	3408
  BCL11A-2924	−	CGAGGCCGAGGGCCACA	17	3409
  BCL11A-2925	+	GUACAUGUGUAGCUGCU	17	3410
  BCL11A-2926	+	UUGAUGCGCUUAGAGAA	17	3411
  BCL11A-2927	+	UCCUCGUCCCCGUUCUC	17	3412
  BCL11A-2928	+	AUGACUUGGACUUGACC	17	3413
  BCL11A-2929	+	GUCUCCGAAGCUAAGGA	17	3414
  BCL11A-2930	+	GGUGGACUAAACAGGGG	17	3415
  BCL11A-2931	+	GCAUGUGCGUCUUCAUG	17	3416
  BCL11A-2932	+	GGCACUCGGGUGAUGGG	17	3417
  BCL11A-2933	+	AUAGGGCUGGGCCGGCC	17	3418
  BCL11A-2934	+	CCGUCCAGCUCCCCGGG	17	3419
  BCL11A-2935	+	GCAGUAACCUUUGCAUA	17	3420
  BCL11A-2936	−	GAUCCCUUCCUUAGCUU	17	3421
  BCL11A-2937	+	AAGGGGCUCAGCGAGCU	17	3422
  BCL11A-2938	−	AGCUGACGGAGAGCGAG	17	3423
  BCL11A-2939	−	UCGCGGGGCGCGGUCGU	17	3424
  BCL11A-2940	−	AGCGGCACGGGAAGUGG	17	3425
  BCL11A-2941	+	CAAAGGCACUCGGGUGA	17	3426
  BCL11A-2942	+	CUGCACCUAGUCCUGAA	17	3427
  BCL11A-2943	−	GCUGGACGGAGGGAUCU	17	3428
  BCL11A-2944	+	CCCUGUCAAAGGCACUC	17	3429
  BCL11A-2945	+	AACCUUUGCAUAGGGCU	17	3430
  BCL11A-2946	+	CGCCCGGGGAGCAGCCG	17	3431
  BCL11A-2947	+	UGGUGGACUAAACAGGG	17	3432
  BCL11A-2948	−	GGCCCAGCCCUAUGCAA	17	3433
  BCL11A-2949	+	CCUCGUCCCCGUUCUCC	17	3434
  BCL11A-2950	−	GCCAGCUCCCCGGAACC	17	3435
  BCL11A-2951	+	GCCGGGUUCCGGGGAGC	17	3436
  BCL11A-2952	+	UGCAGUAACCUUUGCAU	17	3437
  BCL11A-2953	+	GCUUCUCGCCCAGGACC	17	3438
  BCL11A-2954	−	CCGCCCGGGGAGCUGGA	17	3439
  BCL11A-2955	−	CCGGGGAGCUGGACGGA	17	3440
  BCL11A-2956	−	CUUCCGGCCUGGCAGAA	17	3441
  BCL11A-2957	+	CCUAGAGAAAUCCAUGG	17	3442
  BCL11A-2958	+	GGAGGGGGGGCGUCGCC	17	3443
  BCL11A-2959	−	UACUUAGAAAGCGAACA	17	3444
  BCL11A-2960	+	GGAGGCUCCAUAGCCAU	17	3445
  BCL11A-2961	+	ACACAUCUUGAGCUCUC	17	3446
  BCL11A-2962	−	GGCACCAGCGACUUGGU	17	3447
  BCL11A-2963	+	GGGAUCUUUGAGCUGCC	17	3448
  BCL11A-2964	+	GCAGCAGCUUUUUGGAC	17	3449
  BCL11A-2965	+	CUGCAAUAUGAAUCCCA	17	3450
  BCL11A-2966	+	UCUGCACCUAGUCCUGA	17	3451
  BCL11A-2967	+	GAAGGGGCUCAGCGAGC	17	3452
  BCL11A-2968	+	UUCCGGGGAGCUGGCGG	17	3453
  BCL11A-2969	−	GCACCGGCGCAGCCACA	17	3454
  BCL11A-2970	+	AUAUGAAUCCCAUGGAG	17	3455
  BCL11A-2971	−	GUGGUCCGGGCCCGGGC	17	3456
  BCL11A-2972	−	CUUCACACACCCCCAUU	17	3457
  BCL11A-2973	−	GUCCAAAAAGCUGCUGC	17	3458
  BCL11A-2974	−	CGGCACCAGCGACUUGG	17	3459
  BCL11A-2975	−	GCUUCUCCACACCGCCC	17	3460
  BCL11A-2976	+	CGCCCGUGUGGCUGCGC	17	3461
  BCL11A-2977	−	CACGCACAGAACACUCA	17	3462
  BCL11A-2978	+	UGUACAUGUGUAGCUGC	17	3463
  BCL11A-2979	−	CACCGGCGCAGCCACAC	17	3464
  BCL11A-2980	+	UUGCUACCUGGCUGGAA	17	3465
  BCL11A-2981	+	ACCCUGUCAAAGGCACU	17	3466
  BCL11A-2982	−	CCACCUGGCCGAGGCCG	17	3467
  BCL11A-2983	+	GGGCGGAUUGCAGAGGA	17	3468
  BCL11A-2984	+	CUAGAGAAAUCCAUGGC	17	3469
  BCL11A-2985	−	GGCGGAAGAGAUGGCCC	17	3470
  BCL11A-2986	+	GGGGCGGAUUGCAGAGG	17	3471
  BCL11A-2987	−	GUGUGGCAGUUUUCGGA	17	3472
  BCL11A-2988	−	GAGAGAGGCUUCCGGCC	17	3473
  BCL11A-2989	+	CGGGUGAUGGGUGGCCA	17	3474
  BCL11A-2990	−	CCCGGGGAGCUGGACGG	17	3475
  BCL11A-2991	−	UAGGAGACUUAGAGAGC	17	3476
  BCL11A-2992	+	CACAUCUUGAGCUCUCU	17	3477
  BCL11A-2993	+	CCUCGGCCUCGGCCAGG	17	3478
  BCL11A-2994	−	GGCCUUCCACCAGGUCC	17	3479
  BCL11A-2995	+	UCUCGCCCAGGACCUGG	17	3480
  BCL11A-2996	+	UCUGCCCUCUUUUGAGC	17	3481
  BCL11A-2997	+	ACUAAACAGGGGGGGAG	17	3482
  BCL11A-2998	+	CUUGACCGGGGGCUGGG	17	3483
  BCL11A-2999	+	UUGACCGGGGGCUGGGA	17	3484
  BCL11A-3000	−	AGACUUAGAGAGCUGGC	17	3485
  BCL11A-3001	−	AGCCCACCGCUGUCCCC	17	3486
  BCL11A-3002	−	AGCCAUUCACCAGUGCA	17	3487
  BCL11A-3003	−	GCUUCCGGCCUGGCAGA	17	3488
  BCL11A-3004	−	GACUUAGAGAGCUGGCA	17	3489
  BCL11A-3005	−	AGGCCCAGCUCAAAAGA	17	3490
  BCL11A-3006	+	UCGGGUGAUGGGUGGCC	17	3491
  BCL11A-3007	+	CAAGAGAAACCAUGCAC	17	3492
  BCL11A-3008	+	AUCUUUGAGCUGCCUGG	17	3493
  BCL11A-3009	+	UAUUCUUAGCAGGUUAA	17	3494
  BCL11A-3010	+	CUGCCCUCUUUUGAGCU	17	3495
  BCL11A-3011	+	CCAUCUCUUCCGCCCCC	17	3496
  BCL11A-3012	−	UGGCCGCGGCUGCUCCC	17	3497
  BCL11A-3013	+	CCUGUGGCCCUCGGCCU	17	3498
  BCL11A-3014	+	CAGCUCCCCGGGCGGUG	17	3499
  BCL11A-3015	+	UUUGCAUAGGGCUGGGC	17	3500
  BCL11A-3016	+	GGCCCUCGGCCUCGGCC	17	3501
  BCL11A-3017	−	GCUGACGGAGAGCGAGA	17	3502
  BCL11A-3018	−	AGAUGUGUGGCAGUUUU	17	3503
  BCL11A-3019	+	AUUCUUAGCAGGUUAAA	17	3504
  BCL11A-3020	+	UCUCCUAGAGAAAUCCA	17	3505
  BCL11A-3021	−	CCUUUGACAGGGUGCUG	17	3506
  BCL11A-3022	+	GGAGGGGCGGAUUGCAG	17	3507
  BCL11A-3023	+	UUCUUAGCAGGUUAAAG	17	3508
  BCL11A-3024	+	CGGAUUGCAGAGGAGGG	17	3509
  BCL11A-3025	+	UUUGAGCUGGGCCUGCC	17	3510
  BCL11A-3026	+	CUUCAGCUUGCUGGCCU	17	3511
  BCL11A-3027	+	CUUGAACUUGGCCACCA	17	3512
  BCL11A-3028	−	CUGCAACCAUUCCAGCC	17	3513
  BCL11A-3029	−	CAUAGAGCGCCUGGGGG	17	3514
  BCL11A-3030	−	GGGCGCGGUCGUGGGCG	17	3515
  BCL11A-3031	+	UCCCAUGGAGAGGUGGC	17	3516
  BCL11A-3032	−	GGCCGCGGCUGCUCCCC	17	3517
  BCL11A-3033	−	AUUUCAGAGCAACCUGG	17	3518
  BCL11A-3034	−	GCCUUCCACCAGGUCCU	17	3519
  BCL11A-3035	+	UGAAUCCCAUGGAGAGG	17	3520
  BCL11A-3036	+	UUGAGCUGGGCCUGCCC	17	3521
  BCL11A-3037	+	AGGGGCUCAGCGAGCUG	17	3522
  BCL11A-3038	+	AGGGCUUCUCGCCCGUG	17	3523
  BCL11A-3039	−	CACCGCUGUCCCCAGGC	17	3524
  BCL11A-3040	−	CAAAUUUCAGAGCAACC	17	3525
  BCL11A-3041	−	AGAGAGCUCAAGAUGUG	17	3526
  BCL11A-3042	+	AACCAUGCACUGGUGAA	17	3527
  BCL11A-3043	+	CCUCCGUCCAGCUCCCC	17	3528
  BCL11A-3044	+	AGUGUCCCUGUGGCCCU	17	3529
  BCL11A-3045	+	CCCUCCGUCCAGCUCCC	17	3530
  BCL11A-3046	+	GGCCUGGGGACAGCGGU	17	3531
  BCL11A-3047	+	GCCCAGCAGCAGCUUUU	17	3532
  BCL11A-3048	−	CAGGCCCAGCUCAAAAG	17	3533
  BCL11A-3049	−	CUUCGGGCUGAGCCUGG	17	3534
  BCL11A-3050	+	CCCAUGGAGAGGUGGCU	17	3535
  BCL11A-3051	−	CCCAGCCACCUCUCCAU	17	3536
  BCL11A-3052	+	GGGUUCCGGGGAGCUGG	17	3537
  BCL11A-3053	+	UAGGGCUGGGCCGGCCU	17	3538
  BCL11A-3054	−	CCUGGGGGCGGAAGAGA	17	3539
  BCL11A-3055	+	GCCCAGGACCUGGUGGA	17	3540
  BCL11A-3056	−	CGGGCUGAGCCUGGAGG	17	3541
  BCL11A-3057	−	ACCACGAGAACAGCUCG	17	3542
  BCL11A-3058	+	CGGCCUGGGGACAGCGG	17	3543
  BCL11A-3059	−	UCCAAAAAGCUGCUGCU	17	3544
  BCL11A-3060	+	GCGCCCUUCUGCCAGGC	17	3545
  BCL11A-3061	−	UCCCAGCCACCUCUCCA	17	3546
  BCL11A-3062	−	CUCCACCGCCAGCUCCC	17	3547
  BCL11A-3063	+	CUGGGCCUGCCCGGGCC	17	3548
  BCL11A-3064	+	AGGGCUGGGCCGGCCUG	17	3549
  BCL11A-3065	+	AACAGGGGGGGAGUGGG	17	3550
  BCL11A-3066	−	GGAGAACGGGGACGAGG	17	3551
  BCL11A-3067	+	UGAUGCGCUUAGAGAAG	17	3552
  BCL11A-3068	+	GGAUUGCAGAGGAGGGA	17	3553
  BCL11A-3069	+	GGCCGGCCUGGGGACAG	17	3554
  BCL11A-3070	+	GAUUGCAGAGGAGGGAG	17	3555
  BCL11A-3071	+	AUUGCAGAGGAGGGAGG	17	3556
  BCL11A-3072	+	ACCGGGGGCUGGGAGGG	17	3557
  BCL11A-3073	+	UGGAGAGGUGGCUGGGA	17	3558
  BCL11A-3074	+	UUGCAGAGGAGGGAGGG	17	3559
  BCL11A-3075	−	CGGGGACGAGGAGGAAG	17	3560
  BCL11A-3076	−	GACGGAGAGCGAGAGGG	17	3561
  BCL11A-3077	−	UCCUCCCUCCCAGCCCC	17	3562
  BCL11A-3078	+	GCUUCAGCUUGCUGGCC	17	3563
  BCL11A-3079	+	UGCAGAGGAGGGAGGGG	17	3564
  BCL11A-3080	+	GGGCUGGGAGGGAGGAG	17	3565
  BCL11A-3081	−	GGAAGAGGAGGACGACG	17	3566
  BCL11A-3082	+	GGGGCUGGGAGGGAGGA	17	3567
  BCL11A-3083	−	GGAGGACGACGAGGAAG	17	3568
  BCL11A-3084	−	GGAGGAGGAGGAGCUGA	17	3569
  BCL11A-3085	+	GGGGGCUGGGAGGGAGG	17	3570
  BCL11A-3086	+	CUGGGAGGGAGGAGGGG	17	3571
  BCL11A-3087	−	CGAGGAAGAGGAAGAAG	17	3572
  BCL11A-3088	−	GGACGAGGAGGAAGAGG	17	3573
  BCL11A-3089	−	GGAAGAAGAGGAGGAAG	17	3574
  BCL11A-3090	−	GGAAGAGGAAGAAGAGG	17	3575
  BCL11A-3091	−	AGAAGAGGAGGAAGAGG	17	3576
  BCL11A-3092	−	AGAGGAGGAAGAGGAGG	17	3577
  BCL11A-3093	−	GGAGGAAGAGGAGGAGG	17	3578
  BCL11A-3094	+	GUCUAUGCGGUCCGACUCGC	20	3579
  BCL11A-3095	+	UCGUCGGACUUGACCGUCAU	20	3580
  BCL11A-3096	+	CGUCGGACUUGACCGUCAUG	20	3581
  BCL11A-3097	−	AUGACGGUCAAGUCCGACGA	20	3582
  BCL11A-3098	−	GAGUCGGACCGCAUAGACGA	20	3583
  BCL11A-3099	+	CGGGCCCGGACCACUAAUAU	20	3584
  BCL11A-3100	+	GUCGUCGGACUUGACCGUCA	20	3585
  BCL11A-3101	+	CUCUGGGUACUACGCCGAAU	20	3586
  BCL11A-3102	+	CUGGGUACUACGCCGAAUGG	20	3587
  BCL11A-3103	+	CCGGGCCCGGACCACUAAUA	20	3588
  BCL11A-3104	−	CCGCGGGUUGGUAUCCCUUC	20	3589
  BCL11A-3105	+	UCUGGGUACUACGCCGAAUG	20	3590
  BCL11A-3106	+	GGAUACCAACCCGCGGGGUC	20	3591
  BCL11A-3107	−	ACGCCCCAUAUUAGUGGUCC	20	3592
  BCL11A-3108	−	CACUUGCGACGAAGACUCGG	20	3593
  BCL11A-3109	+	UCUCUGGGUACUACGCCGAA	20	3594
  BCL11A-3110	−	UAAGCGCAUCAAGCUCGAGA	20	3595
  BCL11A-3111	−	UGCGACGAAGACUCGGUGGC	20	3596
  BCL11A-3112	+	CGCGCUUAUGCUUCUCGCCC	20	3597
  BCL11A-3113	+	UGAAGGGAUACCAACCCGCG	20	3598
  BCL11A-3114	+	GGGCCCGGACCACUAAUAUG	20	3599
  BCL11A-3115	+	CGUGUUGGGCAUCGCGGCCG	20	3600
  BCL11A-3116	+	UCCGUGUUGGGCAUCGCGGC	20	3601
  BCL11A-3117	+	GUCGGACUUGACCGUCAUGG	20	3602
  BCL11A-3118	+	GCGCAAACUCCCGUUCUCCG	20	3603
  BCL11A-3119	+	CUCCGAGGAGUGCUCCGACG	20	3604
  BCL11A-3120	+	CACGGACUUGAGCGCGCUGC	20	3605
  BCL11A-3121	−	CACGCCCCAUAUUAGUGGUC	20	3606
  BCL11A-3122	+	GAUACCAACCCGCGGGGUCA	20	3607
  BCL11A-3123	−	CAGCGCGCUCAAGUCCGUGG	20	3608
  BCL11A-3124	+	GGGUGCACGCGUGGUCGCAC	20	3609
  BCL11A-3125	−	GAAGCAUAAGCGCGGCCACC	20	3610
  BCL11A-3126	−	GUGCGACCACGCGUGCACCC	20	3611
  BCL11A-3127	+	GAGUACACGUUCUCCGUGUU	20	3612
  BCL11A-3128	+	GUCUCGGUGGUGGACUAAAC	20	3613
  BCL11A-3129	+	CCGUUCUCCGGGAUCAGGUU	20	3614
  BCL11A-3130	+	CGAGUACACGUUCUCCGUGU	20	3615
  BCL11A-3131	−	CGGAGAACGUGUACUCGCAG	20	3616
  BCL11A-3132	−	GGGAGCACGCCCCAUAUUAG	20	3617
  BCL11A-3133	−	CCAUAUUAGUGGUCCGGGCC	20	3618
  BCL11A-3134	+	GCCGCAGAACUCGCAUGACU	20	3619
  BCL11A-3135	+	CGCCCCGCGAGCUGUUCUCG	20	3620
  BCL11A-3136	−	GCAGUGGCUCGCCGGCUACG	20	3621
  BCL11A-3137	−	CAUAUUAGUGGUCCGGGCCC	20	3622
  BCL11A-3138	+	CUGAAGGGAUACCAACCCGC	20	3623
  BCL11A-3139	+	AUACCAACCCGCGGGGUCAG	20	3624
  BCL11A-3140	−	CAGCAGCGCGCUCAAGUCCG	20	3625
  BCL11A-3141	+	CGUCCCCGUUCUCCGGGAUC	20	3626
  BCL11A-3142	−	CACCACGAGAACAGCUCGCG	20	3627
  BCL11A-3143	−	GCGGUUGAAUCCAAUGGCUA	20	3628
  BCL11A-3144	−	GGACACUUGCGACGAAGACU	20	3629
  BCL11A-3145	+	GUGUUGGGCAUCGCGGCCGG	20	3630
  BCL11A-3146	+	CUUCGUCGCAAGUGUCCCUG	20	3631
  BCL11A-3147	+	CCCCAGGCGCUCUAUGCGGU	20	3632
  BCL11A-3148	+	CCGUGUUGGGCAUCGCGGCC	20	3633
  BCL11A-3149	+	CGUUCUCCGGGAUCAGGUUG	20	3634
  BCL11A-3150	+	GCCUCUCUCGAUACUGAUCC	20	3635
  BCL11A-3151	+	UCGCAUGACUUGGACUUGAC	20	3636
  BCL11A-3152	−	AUCACCCGAGUGCCUUUGAC	20	3637
  BCL11A-3153	−	UAAGCGCGGCCACCUGGCCG	20	3638
  BCL11A-3154	−	GCACAAAUCGUCCCCCAUGA	20	3639
  BCL11A-3155	−	CGCCCUGCCCGACGUCAUGC	20	3640
  BCL11A-3156	−	CAACCUGAUCCCGGAGAACG	20	3641
  BCL11A-3157	−	CGGAGCACUCCUCGGAGAAC	20	3642
  BCL11A-3158	−	AGACUCGGUGGCCGGCGAGU	20	3643
  BCL11A-3159	+	GGCGGUGGAGAGACCGUCGU	20	3644
  BCL11A-3160	−	GUGUACUCGCAGUGGCUCGC	20	3645
  BCL11A-3161	−	UCGGAGCACUCCUCGGAGAA	20	3646
  BCL11A-3162	−	CCCGGCCGCGAUGCCCAACA	20	3647
  BCL11A-3163	+	CCCGUUCUCCGGGAUCAGGU	20	3648
  BCL11A-3164	+	UCGGUGGUGGACUAAACAGG	20	3649
  BCL11A-3165	+	CCUGAAGGGAUACCAACCCG	20	3650
  BCL11A-3166	+	GUCGUUCUCGCUCUUGAACU	20	3651
  BCL11A-3167	−	CCCCACCGCAUAGAGCGCCU	20	3652
  BCL11A-3168	+	GUCGCUGGUGCCGGGUUCCG	20	3653
  BCL11A-3169	−	CGAGAACAGCUCGCGGGGCG	20	3654
  BCL11A-3170	+	CGCAUGACUUGGACUUGACC	20	3655
  BCL11A-3171	−	CCCACCGCAUAGAGCGCCUG	20	3656
  BCL11A-3172	+	AAGUCGCUGGUGCCGGGUUC	20	3657
  BCL11A-3173	+	CGAGGAGUGCUCCGACGAGG	20	3658
  BCL11A-3174	−	UCCCCGGGCGAGUCGGCCUC	20	3659
  BCL11A-3175	−	CUCCCCGGGCGAGUCGGCCU	20	3660
  BCL11A-3176	+	CAUGACUUGGACUUGACCGG	20	3661
  BCL11A-3177	−	AGCUCGCGGGGCGCGGUCGU	20	3662
  BCL11A-3178	+	UGCUCCGACGAGGAGGCAAA	20	3663
  BCL11A-3179	+	CUUUUUGGACAGGCCCCCCG	20	3664
  BCL11A-3180	−	CUACGGCUUCGGGCUGAGCC	20	3665
  BCL11A-3181	−	CCCCGGGCGAGUCGGCCUCG	20	3666
  BCL11A-3182	+	UAACAGUGCCAUCGUCUAUG	20	3667
  BCL11A-3183	−	CUCCUCGUCGGAGCACUCCU	20	3668
  BCL11A-3184	−	CCCGGCACCAGCGACUUGGU	20	3669
  BCL11A-3185	−	GCGCUUCUCCACACCGCCCG	20	3670
  BCL11A-3186	+	CUCGGUGGUGGACUAAACAG	20	3671
  BCL11A-3187	−	CCCCCACCGCAUAGAGCGCC	20	3672
  BCL11A-3188	−	GAUCCCGGAGAACGGGGACG	20	3673
  BCL11A-3189	+	CCAGGCGCUCUAUGCGGUGG	20	3674
  BCL11A-3190	−	UUAGUGGUCCGGGCCCGGGC	20	3675
  BCL11A-3191	+	CCCAGGCGCUCUAUGCGGUG	20	3676
  BCL11A-3192	−	CGGCUGCUCCCCGGGCGAGU	20	3677
  BCL11A-3193	−	UCGCCGGCUACGCGGCCUCC	20	3678
  BCL11A-3194	−	AUCGAGAGAGGCUUCCGGCC	20	3679
  BCL11A-3195	+	GGGUCCAAGUGAUGUCUCGG	20	3680
  BCL11A-3196	−	AUCGCCUUUUGCCUCCUCGU	20	3681
  BCL11A-3197	−	AUCUCGGGGCGCAGCGGCAC	20	3682
  BCL11A-3198	+	CGGUGGUGGACUAAACAGGG	20	3683
  BCL11A-3199	−	GAUGGCACUGUUAAUGGCCG	20	3684
  BCL11A-3200	+	UGCCCUGCAUGACGUCGGGC	20	3685
  BCL11A-3201	+	UCUCGGUGGUGGACUAAACA	20	3686
  BCL11A-3202	−	AGAGGGUGGACUACGGCUUC	20	3687
  BCL11A-3203	+	CCCCGAGGCCGACUCGCCCG	20	3688
  BCL11A-3204	−	GAUCUCGGGGCGCAGCGGCA	20	3689
  BCL11A-3205	−	ACGGAAGUCCCCUGACCCCG	20	3690
  BCL11A-3206	+	ACUCGCCCGGGGAGCAGCCG	20	3691
  BCL11A-3207	−	UUGCGCUUCUCCACACCGCC	20	3692
  BCL11A-3208	−	GGAACCCGGCACCAGCGACU	20	3693
  BCL11A-3209	+	GCAUGACUUGGACUUGACCG	20	3694
  BCL11A-3210	−	UAAUGGCCGCGGCUGCUCCC	20	3695
  BCL11A-3211	−	CCGGGCGAGUCGGCCUCGGG	20	3696
  BCL11A-3212	+	GUCAAAGGCACUCGGGUGAU	20	3697
  BCL11A-3213	−	GGUGCUGCGGUUGAAUCCAA	20	3698
  BCL11A-3214	−	CUGGGCGAGAAGCAUAAGCG	20	3699
  BCL11A-3215	+	ACUUGGACUUGACCGGGGGC	20	3700
  BCL11A-3216	+	CCCCCCGAGGCCGACUCGCC	20	3701
  BCL11A-3217	−	CCACCGCAUAGAGCGCCUGG	20	3702
  BCL11A-3218	+	AGUCGCUGGUGCCGGGUUCC	20	3703
  BCL11A-3219	+	UCGCACAGGUUGCACUUGUA	20	3704
  BCL11A-3220	+	GCCCUGCAUGACGUCGGGCA	20	3705
  BCL11A-3221	+	CCGCCCCCAGGCGCUCUAUG	20	3706
  BCL11A-3222	−	GCCCUGCCCGACGUCAUGCA	20	3707
  BCL11A-3223	+	GUCGCACAGGUUGCACUUGU	20	3708
  BCL11A-3224	−	AGGUAGCAAGCCGCCCUUCC	20	3709
  BCL11A-3225	−	CCAACCUGAUCCCGGAGAAC	20	3710
  BCL11A-3226	+	AGGAAGGGCGGCUUGCUACC	20	3711
  BCL11A-3227	−	GAAGGAGUUCGACCUGCCCC	20	3712
  BCL11A-3228	+	CUUGGACUUGACCGGGGGCU	20	3713
  BCL11A-3229	−	GAGAGGGUGGACUACGGCUU	20	3714
  BCL11A-3230	−	UCCAAGUCAUGCGAGUUCUG	20	3715
  BCL11A-3231	−	ACCCGGCACCAGCGACUUGG	20	3716
  BCL11A-3232	+	CCCCCAGGCGCUCUAUGCGG	20	3717
  BCL11A-3233	+	GCGUCUGCCCUCUUUUGAGC	20	3718
  BCL11A-3234	−	GCCCGACGUCAUGCAGGGCA	20	3719
  BCL11A-3235	+	GAGCUUGAUGCGCUUAGAGA	20	3720
  BCL11A-3236	−	CAGCUCGCGGGGCGCGGUCG	20	3721
  BCL11A-3237	+	CGUGGUGGCGCGCCGCCUCC	20	3722
  BCL11A-3238	−	UCACCCGAGUGCCUUUGACA	20	3723
  BCL11A-3239	−	GAACGACCCCAACCUGAUCC	20	3724
  BCL11A-3240	+	CAACCGCAGCACCCUGUCAA	20	3725
  BCL11A-3241	+	UCCAAGUGAUGUCUCGGUGG	20	3726
  BCL11A-3242	+	GUUCUCCGUGUUGGGCAUCG	20	3727
  BCL11A-3243	−	CGGAAGUCCCCUGACCCCGC	20	3728
  BCL11A-3244	+	UAUGCUUCUCGCCCAGGACC	20	3729
  BCL11A-3245	−	AGCUGGACGGAGGGAUCUCG	20	3730
  BCL11A-3246	+	GGCUGCGCCGGUGCACCACC	20	3731
  BCL11A-3247	−	GUUGGUAUCCCUUCAGGACU	20	3732
  BCL11A-3248	−	AUAGACGAUGGCACUGUUAA	20	3733
  BCL11A-3249	−	CUCCCGCCAUGGAUUUCUCU	20	3734
  BCL11A-3250	−	ACCAGGAUCAGUAUCGAGAG	20	3735
  BCL11A-3251	−	AGUCCCCUGACCCCGCGGGU	20	3736
  BCL11A-3252	+	GUCUGGAGUCUCCGAAGCUA	20	3737
  BCL11A-3253	−	GCCGGCCCAGCCCUAUGCAA	20	3738
  BCL11A-3254	−	GAUGUGUGGCAGUUUUCGGA	20	3739
  BCL11A-3255	+	CUAGAGAAAUCCAUGGCGGG	20	3740
  BCL11A-3256	+	GGCGCUGCCCACCAAGUCGC	20	3741
  BCL11A-3257	−	CCCGGGCGAGUCGGCCUCGG	20	3742
  BCL11A-3258	−	ACACCGCCCGGGGAGCUGGA	20	3743
  BCL11A-3259	+	CAGUAACCUUUGCAUAGGGC	20	3744
  BCL11A-3260	−	UCAGUAUCGAGAGAGGCUUC	20	3745
  BCL11A-3261	+	GCAUGACGUCGGGCAGGGCG	20	3746
  BCL11A-3262	−	CCGCAUAGAGCGCCUGGGGG	20	3747
  BCL11A-3263	+	CCCCCGAGGCCGACUCGCCC	20	3748
  BCL11A-3264	+	AGGGCGGCUUGCUACCUGGC	20	3749
  BCL11A-3265	+	GCACCCUGUCAAAGGCACUC	20	3750
  BCL11A-3266	+	CUGAUCCUGGUAUUCUUAGC	20	3751
  BCL11A-3267	+	CAUGUGGCGCUUCAGCUUGC	20	3752
  BCL11A-3268	+	CCCACCAAGUCGCUGGUGCC	20	3753
  BCL11A-3269	+	GGAGGCAAAAGGCGAUUGUC	20	3754
  BCL11A-3270	−	CCCAACCUGAUCCCGGAGAA	20	3755
  BCL11A-3271	+	GAGUCUCCGAAGCUAAGGAA	20	3756
  BCL11A-3272	−	GGCUAUGGAGCCUCCCGCCA	20	3757
  BCL11A-3273	+	CGUCUGCCCUCUUUUGAGCU	20	3758
  BCL11A-3274	−	CGCCCGGGGAGCUGGACGGA	20	3759
  BCL11A-3275	+	AGUAACCUUUGCAUAGGGCU	20	3760
  BCL11A-3276	−	UCCACCACCGAGACAUCACU	20	3761
  BCL11A-3277	+	GGUUGCAGUAACCUUUGCAU	20	3762
  BCL11A-3278	+	GCAAUAUGAAUCCCAUGGAG	20	3763
  BCL11A-3279	+	ACCAUGCCCUGCAUGACGUC	20	3764
  BCL11A-3280	+	GGCCUCGCUGAAGUGCUGCA	20	3765
  BCL11A-3281	−	AGAGCAACCUGGUGGUGCAC	20	3766
  BCL11A-3282	+	GCCCACCAAGUCGCUGGUGC	20	3767
  BCL11A-3283	+	UGUCAAAGGCACUCGGGUGA	20	3768
  BCL11A-3284	+	AGCUUGAUGCGCUUAGAGAA	20	3769
  BCL11A-3285	+	AGGGGGGGCGUCGCCAGGAA	20	3770
  BCL11A-3286	+	GUGGAAAGCGCCCUUCUGCC	20	3771
  BCL11A-3287	+	UGGGGGUCCAAGUGAUGUCU	20	3772
  BCL11A-3288	−	CUCCAUGCAGCACUUCAGCG	20	3773
  BCL11A-3289	+	GCGCUUCAGCUUGCUGGCCU	20	3774
  BCL11A-3290	−	CUUCAGCGAGGCCUUCCACC	20	3775
  BCL11A-3291	+	GGAGUCUCCGAAGCUAAGGA	20	3776
  BCL11A-3292	+	CACUCGGGUGAUGGGUGGCC	20	3777
  BCL11A-3293	−	UGCGCUUCUCCACACCGCCC	20	3778
  BCL11A-3294	+	GGUGGUGGACUAAACAGGGG	20	3779
  BCL11A-3295	−	CGAGGCCUUCCACCAGGUCC	20	3780
  BCL11A-3296	−	AAUGGCCGCGGCUGCUCCCC	20	3781
  BCL11A-3297	+	GUUGUACAUGUGUAGCUGCU	20	3782
  BCL11A-3298	−	GUUCUUCACACACCCCCAUU	20	3783
  BCL11A-3299	−	CGCAGCGGCACGGGAAGUGG	20	3784
  BCL11A-3300	+	GCGGGAGGCUCCAUAGCCAU	20	3785
  BCL11A-3301	−	GGUGCACCGGCGCAGCCACA	20	3786
  BCL11A-3302	−	CUCCACACCGCCCGGGGAGC	20	3787
  BCL11A-3303	+	AAAGCGCCCUUCUGCCAGGC	20	3788
  BCL11A-3304	+	ACUCGGGUGAUGGGUGGCCA	20	3789
  BCL11A-3305	+	CUGCCUGGAGGCCGCGUAGC	20	3790
  BCL11A-3306	+	GUCCAGCUCCCCGGGCGGUG	20	3791
  BCL11A-3307	−	GAGCUGGACGGAGGGAUCUC	20	3792
  BCL11A-3308	−	UCUAGCCCACCGCUGUCCCC	20	3793
  BCL11A-3309	+	AGUUGUACAUGUGUAGCUGC	20	3794
  BCL11A-3310	+	AUUCUGCACCUAGUCCUGAA	20	3795
  BCL11A-3311	−	CCACCACGAGAACAGCUCGC	20	3796
  BCL11A-3312	+	CUCCUAGAGAAAUCCAUGGC	20	3797
  BCL11A-3313	−	UUUAACCUGCUAAGAAUACC	20	3798
  BCL11A-3314	+	GGACUAAACAGGGGGGGAGU	20	3799
  BCL11A-3315	−	GGCCACCUGGCCGAGGCCGA	20	3800
  BCL11A-3316	+	GGCUUGCUACCUGGCUGGAA	20	3801
  BCL11A-3317	+	CAUUCUGCACCUAGUCCUGA	20	3802
  BCL11A-3318	+	UGCUGGCCUGGGUGCACGCG	20	3803
  BCL11A-3319	+	UGUGGCCCUCGGCCUCGGCC	20	3804
  BCL11A-3320	−	CCGCCCGGGGAGCUGGACGG	20	3805
  BCL11A-3321	−	UGGCCGAGGCCGAGGGCCAC	20	3806
  BCL11A-3322	+	UGGGCAUCGCGGCCGGGGGC	20	3807
  BCL11A-3323	+	UCUCCUAGAGAAAUCCAUGG	20	3808
  BCL11A-3324	+	GGGCCAUCUCUUCCGCCCCC	20	3809
  BCL11A-3325	+	GUUGCAGUAACCUUUGCAUA	20	3810
  BCL11A-3326	+	AAAGGCACUCGGGUGAUGGG	20	3811
  BCL11A-3327	+	GAAGGGAUCUUUGAGCUGCC	20	3812
  BCL11A-3328	+	GCCACACAUCUUGAGCUCUC	20	3813
  BCL11A-3329	−	GGAGGGAUCUCGGGGCGCAG	20	3814
  BCL11A-3330	−	CCCGGAGAACGGGGACGAGG	20	3815
  BCL11A-3331	+	UGCAUAGGGCUGGGCCGGCC	20	3816
  BCL11A-3332	−	CGGGGCGCGGUCGUGGGCGU	20	3817
  BCL11A-3333	+	GAGGGGGGGCGUCGCCAGGA	20	3818
  BCL11A-3334	−	ACCGCCAGCUCCCCGGAACC	20	3819
  BCL11A-3335	+	GGUAUUCUUAGCAGGUUAAA	20	3820
  BCL11A-3336	−	AGGCUUCCGGCCUGGCAGAA	20	3821
  BCL11A-3337	+	GAUCCCUCCGUCCAGCUCCC	20	3822
  BCL11A-3338	+	UGGUAUUCUUAGCAGGUUAA	20	3823
  BCL11A-3339	−	AUCUACUUAGAAAGCGAACA	20	3824
  BCL11A-3340	−	CGGCCACCUGGCCGAGGCCG	20	3825
  BCL11A-3341	−	CAACACGCACAGAACACUCA	20	3826
  BCL11A-3342	+	GCCGGCCUGGGGACAGCGGU	20	3827
  BCL11A-3343	−	GCCACCACGAGAACAGCUCG	20	3828
  BCL11A-3344	+	GUAUUCUUAGCAGGUUAAAG	20	3829
  BCL11A-3345	−	CUCUAGGAGACUUAGAGAGC	20	3830
  BCL11A-3346	−	AACAGCCAUUCACCAGUGCA	20	3831
  BCL11A-3347	+	UUGCAAGAGAAACCAUGCAC	20	3832
  BCL11A-3348	+	GACUUGACCGGGGGCUGGGA	20	3833
  BCL11A-3349	+	ACCUUUGCAUAGGGCUGGGC	20	3834
  BCL11A-3350	+	UCUUUUGAGCUGGGCCUGCC	20	3835
  BCL11A-3351	−	GAGGCCUUCCACCAGGUCCU	20	3836
  BCL11A-3352	+	CUUUUGAGCUGGGCCUGCCC	20	3837
  BCL11A-3353	+	GGGAUCUUUGAGCUGCCUGG	20	3838
  BCL11A-3354	−	GGGCAGGCCCAGCUCAAAAG	20	3839
  BCL11A-3355	+	AGCACCCUGUCAAAGGCACU	20	3840
  BCL11A-3356	+	UGGACUAAACAGGGGGGGAG	20	3841
  BCL11A-3357	+	GCUCUUGAACUUGGCCACCA	20	3842
  BCL11A-3358	+	GAAUCCCAUGGAGAGGUGGC	20	3843
  BCL11A-3359	−	GUGCACCGGCGCAGCCACAC	20	3844
  BCL11A-3360	−	AAAGAUCCCUUCCUUAGCUU	20	3845
  BCL11A-3361	+	UGUCUGCAAUAUGAAUCCCA	20	3846
  BCL11A-3362	−	GGCAGGCCCAGCUCAAAAGA	20	3847
  BCL11A-3363	+	CCUCCGUCCAGCUCCCCGGG	20	3848
  BCL11A-3364	−	CUGUCCAAAAAGCUGCUGCU	20	3849
  BCL11A-3365	+	GCUUGAUGCGCUUAGAGAAG	20	3850
  BCL11A-3366	−	CGGCUUCGGGCUGAGCCUGG	20	3851
  BCL11A-3367	+	CACCAUGCCCUGCAUGACGU	20	3852
  BCL11A-3368	−	UCAAGAUGUGUGGCAGUUUU	20	3853
  BCL11A-3369	−	GUUCAAAUUUCAGAGCAACC	20	3854
  BCL11A-3370	+	GAGAAGGGGCUCAGCGAGCU	20	3855
  BCL11A-3371	−	GCAGCGGCACGGGAAGUGGA	20	3856
  BCL11A-3372	+	AAGUCUCCUAGAGAAAUCCA	20	3857
  BCL11A-3373	+	GGUGCCGGGUUCCGGGGAGC	20	3858
  BCL11A-3374	−	CCUGUCCAAAAAGCUGCUGC	20	3859
  BCL11A-3375	+	AUAUGAAUCCCAUGGAGAGG	20	3860
  BCL11A-3376	−	GGGCGCAGCGGCACGGGAAG	20	3861
  BCL11A-3377	−	GGCCGAGGCCGAGGGCCACA	20	3862
  BCL11A-3378	+	GCAAGUGUCCCUGUGGCCCU	20	3863
  BCL11A-3379	+	GGACUUGACCGGGGGCUGGG	20	3864
  BCL11A-3380	+	GCUUCUCGCCCAGGACCUGG	20	3865
  BCL11A-3381	−	GCGCCUGGGGGCGGAAGAGA	20	3866
  BCL11A-3382	+	GUCCCUGUGGCCCUCGGCCU	20	3867
  BCL11A-3383	+	AUCCCUCCGUCCAGCUCCCC	20	3868
  BCL11A-3384	−	GUGCCUUUGACAGGGUGCUG	20	3869
  BCL11A-3385	−	CCCAGAGAGCUCAAGAUGUG	20	3870
  BCL11A-3386	+	GGCCCUCGGCCUCGGCCAGG	20	3871
  BCL11A-3387	−	GAGAGCGAGAGGGUGGACUA	20	3872
  BCL11A-3388	+	GGGGGCGUCGCCAGGAAGGG	20	3873
  BCL11A-3389	+	AGAGAAGGGGCUCAGCGAGC	20	3874
  BCL11A-3390	+	CCACACAUCUUGAGCUCUCU	20	3875
  BCL11A-3391	+	GCUGCCCAGCAGCAGCUUUU	20	3876
  BCL11A-3392	−	GGAGCUGGACGGAGGGAUCU	20	3877
  BCL11A-3393	−	GGGGGCGGAAGAGAUGGCCC	20	3878
  BCL11A-3394	−	AGGAGACUUAGAGAGCUGGC	20	3879
  BCL11A-3395	−	GAGGCUUCCGGCCUGGCAGA	20	3880
  BCL11A-3396	+	AAUCCCAUGGAGAGGUGGCU	20	3881
  BCL11A-3397	+	UGUGCAUGUGCGUCUUCAUG	20	3882
  BCL11A-3398	+	CUCGCCCAGGACCUGGUGGA	20	3883
  BCL11A-3399	+	UCCUCCUCGUCCCCGUUCUC	20	3884
  BCL11A-3400	+	AGAAACCAUGCACUGGUGAA	20	3885
  BCL11A-3401	−	CUUCGGGCUGAGCCUGGAGG	20	3886
  BCL11A-3402	+	GCCGGGUUCCGGGGAGCUGG	20	3887
  BCL11A-3403	+	AGAAGGGGCUCAGCGAGCUG	20	3888
  BCL11A-3404	+	CUAAACAGGGGGGGAGUGGG	20	3889
  BCL11A-3405	−	CAAAUUUCAGAGCAACCUGG	20	3890
  BCL11A-3406	+	GAGGGAGGGGGGGCGUCGCC	20	3891
  BCL11A-3407	+	CCUCCUCGUCCCCGUUCUCC	20	3892
  BCL11A-3408	+	CCAGCAGCAGCUUUUUGGAC	20	3893
  BCL11A-3409	−	GCCCACCGCUGUCCCCAGGC	20	3894
  BCL11A-3410	−	GGAGACUUAGAGAGCUGGCA	20	3895
  BCL11A-3411	−	AGGAGCUGACGGAGAGCGAG	20	3896
  BCL11A-3412	+	GAGGGGCGGAUUGCAGAGGA	20	3897
  BCL11A-3413	+	CAUAGGGCUGGGCCGGCCUG	20	3898
  BCL11A-3414	+	GGCGGAUUGCAGAGGAGGGA	20	3899
  BCL11A-3415	+	GGAGGGGCGGAUUGCAGAGG	20	3900
  BCL11A-3416	−	UUACUGCAACCAUUCCAGCC	20	3901
  BCL11A-3417	+	GCAUAGGGCUGGGCCGGCCU	20	3902
  BCL11A-3418	+	GGGCGGAUUGCAGAGGAGGG	20	3903
  BCL11A-3419	+	GGGUUCCGGGGAGCUGGCGG	20	3904
  BCL11A-3420	+	UCUCGCCCGUGUGGCUGCGC	20	3905
  BCL11A-3421	−	CUUCCCAGCCACCUCUCCAU	20	3906
  BCL11A-3422	−	GCUGACGGAGAGCGAGAGGG	20	3907
  BCL11A-3423	+	GCGGAUUGCAGAGGAGGGAG	20	3908
  BCL11A-3424	−	GGAGCUGACGGAGAGCGAGA	20	3909
  BCL11A-3425	−	UCUCUCCACCGCCAGCUCCC	20	3910
  BCL11A-3426	+	UUGACCGGGGGCUGGGAGGG	20	3911
  BCL11A-3427	+	CGGAUUGCAGAGGAGGGAGG	20	3912
  BCL11A-3428	−	GCGGGGCGCGGUCGUGGGCG	20	3913
  BCL11A-3429	+	GAGCUGGGCCUGCCCGGGCC	20	3914
  BCL11A-3430	+	CUGGGCCGGCCUGGGGACAG	20	3915
  BCL11A-3431	+	UGUAGGGCUUCUCGCCCGUG	20	3916
  BCL11A-3432	+	CCAUGGAGAGGUGGCUGGGA	20	3917
  BCL11A-3433	+	GGAGGAGGGGCGGAUUGCAG	20	3918
  BCL11A-3434	−	CCUUCCCAGCCACCUCUCCA	20	3919
  BCL11A-3435	+	CCCGCGAGCUGUUCUCGUGG	20	3920
  BCL11A-3436	+	GAUUGCAGAGGAGGGAGGGG	20	3921
  BCL11A-3437	+	GGCCGGCCUGGGGACAGCGG	20	3922
  BCL11A-3438	+	GGAUUGCAGAGGAGGGAGGG	20	3923
  BCL11A-3439	+	ACCGGGGGCUGGGAGGGAGG	20	3924
  BCL11A-3440	+	CCGGGGGCUGGGAGGGAGGA	20	3925
  BCL11A-3441	−	GAACGGGGACGAGGAGGAAG	20	3926
  BCL11A-3442	−	CCCUCCUCCCUCCCAGCCCC	20	3927
  BCL11A-3443	+	CGGGGGCUGGGAGGGAGGAG	20	3928
  BCL11A-3444	+	GGCGCUUCAGCUUGCUGGCC	20	3929
  BCL11A-3445	−	CGGGGACGAGGAGGAAGAGG	20	3930
  BCL11A-3446	−	AGAGGAGGAGGAGGAGCUGA	20	3931
  BCL11A-3447	+	GGGCUGGGAGGGAGGAGGGG	20	3932
  BCL11A-3448	−	AGAGGAGGACGACGAGGAAG	20	3933
  BCL11A-3449	−	CGACGAGGAAGAGGAAGAAG	20	3934
  BCL11A-3450	−	GGAGGAAGAGGAGGACGACG	20	3935
  BCL11A-3451	−	CGAGGAAGAGGAAGAAGAGG	20	3936
  BCL11A-3452	−	GGAAGAAGAGGAGGAAGAGG	20	3937
  BCL11A-3453	−	AGAGGAAGAAGAGGAGGAAG	20	3938
  BCL11A-3454	−	AGAAGAGGAGGAAGAGGAGG	20	3939
  BCL11A-3455	−	AGAGGAGGAAGAGGAGGAGG	20	3940

• Table 5A 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 bind within first 500 bp 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 0-50 bp.
• 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 5A
  			Target	SEQ
  	DNA		Site	ID
  gRNA Name	Strand	Targeting Domain	Length	NO
  BCL11A-3456	−	GAACCAGACCACGGCCCGUU	20	3941
  BCL11A-3457	+	GACCUGGAUGCCAACCUCCA	20	3942
  BCL11A-3458	+	GAUUAGAGCUCCAUGUG	17	3943
  BCL11A-3459	−	GAUUGUUUAUCAACGUCAUC	20	3944
  BCL11A-3460	+	GCACUCAUCCCAGGCGU	17	3945
  BCL11A-3461	+	GGGGAUUAGAGCUCCAUGUG	20	3946
  BCL11A-3462	−	GUGCAGAAUAUGCCCCG	17	3947

• 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 bind within first 500 bp 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.
• 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 0-50 bp.
• 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 BCL43A gene, e.g., the first pair of gRNAs are used to target upstream (i.e., 5′) of the enhancer region in the BCL3A gene and the second pair of gRNAs are used to target downstream (i.e., 3′) of the enhancer region in the BCL11A gene.

• TABLE 5B
  2nd Tier

  			Target	SEQ
  	DNA		Site	ID
  gRNA Name	Strand	Targeting Domain	Length	NO
  BCL11A-3463	−	AACCAGACCACGGCCCG	17	3948
  BCL11A-3464	+	AAUUCCCGUUUGCUUAAGUG	20	3949
  BCL11A-3465	−	ACCAGACCACGGCCCGU	17	3950
  BCL11A-3466	−	AUGAACCAGACCACGGCCCG	20	3951
  BCL11A-3467	+	AUUCCCGUUUGCUUAAGUGC	20	3952
  BCL11A-3468	−	CCAGACCACGGCCCGUU	17	3953
  BCL11A-3469	+	CCCGUUUGCUUAAGUGC	17	3954
  BCL11A-3470	+	CCUGGAUGCCAACCUCC	17	3955
  BCL11A-3471	+	CUGGAUGCCAACCUCCA	17	3956
  BCL11A-3472	+	UCAUCCUCUGGCGUGAC	17	3957
  BCL11A-3473	+	UCCCGUUUGCUUAAGUG	17	3958
  BCL11A-3474	+	UCGUCAUCCUCUGGCGUGAC	20	3959
  BCL11A-3475	+	UCUGCACUCAUCCCAGGCGU	20	3960
  BCL11A-3476	+	UCUGGUUCAUCAUCUGU	17	3961
  BCL11A-3477	−	UGAACCAGACCACGGCCCGU	20	3962
  BCL11A-3478	+	UGACCUGGAUGCCAACCUCC	20	3963
  BCL11A-3479	−	UGAGUGCAGAAUAUGCCCCG	20	3964
  BCL11A-3480	+	UGCACUCAUCCCAGGCG	17	3965
  BCL11A-3481	+	UGGUCUGGUUCAUCAUCUGU	20	3966
  BCL11A-3482	−	UGUUUAUCAACGUCAUC	17	3967
  BCL11A-3483	−	UGUUUAUCAACGUCAUCUAG	20	3968
  BCL11A-3484	−	UUAUCAACGUCAUCUAG	17	3969
  BCL11A-3485	+	UUCUGCACUCAUCCCAGGCG	20	3970
  BCL11A-3486	−	UUGUUUAUCAACGUCAUCUA	20	3971
  BCL11A-3487	−	UUUAUCAACGUCAUCUA	17	3972

• Table 5C 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 bind within first 500 bp 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.
• 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 0-50 bp.
• 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 5C
  3rd Tier			Target	SEQ
  gRNA	DNA	Targeting	Site	ID
  Name	Strand	Domain	Length	NO
  BCL11A-3488	−	GAAAAAAGCAUCCAAUCCCG	20	3973
  BCL11A-3489	+	GAGAGGCCCCUCCAGUG	17	3974
  BCL11A-3490	+	GAGCUCCAUGUGCAGAACGA	20	3975
  BCL11A-3491	−	GAGGAAUUUGCCCCAAA	17	3976
  BCL11A-3492	+	GAGGAGAGGCCCCUCCAGUG	20	3977
  BCL11A-3493	+	GAGGAGGUCAUGAUCCCCUU	20	3978
  BCL11A-3494	+	GAGGUCAUGAUCCCCUU	17	3979
  BCL11A-3495	−	GCAUCCAGGUCACGCCA	17	3980
  BCL11A-3496	−	GCCACCUUCCCCUUCACCAA	20	3981
  BCL11A-3497	−	GCCAGAUGAACUUCCCA	17	3982
  BCL11A-3498	−	GCCAGAUGAACUUCCCAUUG	20	3983
  BCL11A-3499	−	GCCCGUUGGGAGCUCCAGAA	20	3984
  BCL11A-3500	−	GCCUCUGCUUAGAAAAAGCU	20	3985
  BCL11A-3501	+	GCUCCAUGUGCAGAACG	17	3986
  BCL11A-3502	−	GCUCUAAUCCCCACGCC	17	3987
  BCL11A-3503	−	GGACAUUCUUAUUUUUA	17	3988
  BCL11A-3504	−	GGAGCUCUAAUCCCCACGCC	20	3989
  BCL11A-3505	−	GGAUCAUGACCUCCUCACCU	20	3990
  BCL11A-3506	+	GGAUGCCAACCUCCACGGGA	20	3991
  BCL11A-3507	+	GGCACUGCCCACAGGUG	17	3992
  BCL11A-3508	−	GGCCCGUUGGGAGCUCCAGA	20	3993
  BCL11A-3509	−	GGGGGACAUUCUUAUUUUUA	20	3994
  BCL11A-3510	−	GGUUGGCAUCCAGGUCACGC	20	3995
  BCL11A-3511	+	GGUUUGCCUUGCUUGCG	17	3996
  BCL11A-3512	+	GUGCAGAACGAGGGGAG	17	3997
  BCL11A-3513	−	GUGCCAGAUGAACUUCCCAU	20	3998

• Table 5D provides exemplary targeting domains for knocking out the BCL11A gene by targeting the early coding sequence the BCL11A gene selected according to forth tier parameters. The targeting domains bind within first 500 bp 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 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 0-50 bp.
• 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 BCL4A gene and the second pair of gRNAs are used to target downstream (i.e., 3′) of the enhancer region in the BCL11A gene.

• TABLE 5D
  			Target	SEQ
  4th Tier	DNA	Targeting	Site	ID
  gRNA Name	Strand	Domain	Length	NO
  BCL11A-3514	−	AAAAAGCAUCCAAUCCC	17	3999
  BCL11A-3515	+	AAAAAUAAGAAUGUCCCCCA	20	4000
  BCL11A-3516	−	AAAAGCAUCCAAUCCCG	17	4001
  BCL11A-3517	+	AAAAUAAGAAUGUCCCCCAA	20	4002
  BCL11A-3518	−	AAACCCCAGCACUUAAGCAA	20	4003
  BCL11A-3519	+	AAAUAAGAAUGUCCCCCAAU	20	4004
  BCL11A-3520	−	AACCCCAGCACUUAAGCAAA	20	4005
  BCL11A-3521	+	AAUAAGAAUGUCCCCCA	17	4006
  BCL11A-3522	−	ACCCCAGCACUUAAGCAAAC	20	4007
  BCL11A-3523	−	ACCUUCCCCUUCACCAA	17	4008
  BCL11A-3524	+	AGAGCUCCAUGUGCAGA	17	4009
  BCL11A-3525	+	AGAGCUCCAUGUGCAGAACG	20	4010
  BCL11A-3526	−	AGAUGAACUUCCCAUUG	17	4011
  BCL11A-3527	−	AGCCAUUCUUACAGAUG	17	4012
  BCL11A-3528	+	AGCUCCAUGUGCAGAAC	17	4013
  BCL11A-3529	+	AGCUCCAUGUGCAGAACGAG	20	4014
  BCL11A-3530	−	AGCUCUAAUCCCCACGC	17	4015
  BCL11A-3531	−	AGGAAUUUGCCCCAAAC	17	4016
  BCL11A-3532	+	AGGAGGUCAUGAUCCCCUUC	20	4017
  BCL11A-3533	+	AGGUCAUGAUCCCCUUC	17	4018
  BCL11A-3534	−	AGUGCCAGAUGAACUUCCCA	20	4019
  BCL11A-3535	+	AUAAGAAUGUCCCCCAA	17	4020
  BCL11A-3536	+	AUCCCAGGCGUGGGGAU	17	4021
  BCL11A-3537	+	AUCCCCUUCUGGAGCUCCCA	20	4022
  BCL11A-3538	+	AUCUGGCACUGCCCACAGGU	20	4023
  BCL11A-3539	−	AUGCAAUGGCAGCCUCUGCU	20	4024
  BCL11A-3540	+	AUGUGCAGAACGAGGGG	17	4025
  BCL11A-3541	+	AUUAGAGCUCCAUGUGCAGA	20	4026
  BCL11A-3542	+	AUUCUGCACUCAUCCCAGGC	20	4027
  BCL11A-3543	−	AUUUUUAUCGAGCACAA	17	4028
  BCL11A-3544	−	CAAUGGCAGCCUCUGCU	17	4029
  BCL11A-3545	−	CACGCCUGGGAUGAGUG	17	4030
  BCL11A-3546	−	CAGAUGAACUUCCCAUU	17	4031
  BCL11A-3547	+	CAUCUCGAUUGGUGAAG	17	4032
  BCL11A-3548	+	CAUGUGCAGAACGAGGG	17	4033
  BCL11A-3549	+	CAUGUGCAGAACGAGGGGAG	20	4034
  BCL11A-3550	+	CCACAGCUUUUUCUAAG	17	4035
  BCL11A-3551	−	CCACGGCCCGUUGGGAGCUC	20	4036
  BCL11A-3552	−	CCAGAUGAACUUCCCAU	17	4037
  BCL11A-3553	−	CCAGCACUUAAGCAAAC	17	4038
  BCL11A-3554	−	CCCAGCACUUAAGCAAA	17	4039
  BCL11A-3555	−	CCCCACGCCUGGGAUGAGUG	20	4040
  BCL11A-3556	−	CCCCAGCACUUAAGCAA	17	4041
  BCL11A-3557	−	CCCCUUCACCAAUCGAG	17	4042
  BCL11A-3558	−	CCCGUUGGGAGCUCCAG	17	4043
  BCL11A-3559	+	CCCUUCUGGAGCUCCCA	17	4044
  BCL11A-3560	−	CCGUUGGGAGCUCCAGA	17	4045
  BCL11A-3561	−	CCUGUGGGCAGUGCCAG	17	4046
  BCL11A-3562	−	CGGCCCGUUGGGAGCUC	17	4047
  BCL11A-3563	−	CGGCCCGUUGGGAGCUCCAG	20	4048
  BCL11A-3564	−	CGUUGGGAGCUCCAGAA	17	4049
  BCL11A-3565	+	CGUUUGUGCUCGAUAAAAAU	20	4050
  BCL11A-3566	−	CUAGAGGAAUUUGCCCCAAA	20	4051
  BCL11A-3567	+	CUCAUCCCAGGCGUGGGGAU	20	4052
  BCL11A-3568	+	CUCCAUGUGCAGAACGA	17	4053
  BCL11A-3569	+	CUCCAUGUGCAGAACGAGGG	20	4054
  BCL11A-3570	−	CUCCCCUCGUUCUGCAC	17	4055
  BCL11A-3571	−	CUCCUCCCCUCGUUCUGCAC	20	4056
  BCL11A-3572	−	CUCUAAUCCCCACGCCUGGG	20	4057
  BCL11A-3573	+	CUGCACUCAUCCCAGGC	17	4058
  BCL11A-3574	−	CUUAUUUUUAUCGAGCACAA	20	4059
  BCL11A-3575	−	CUUCCCCUUCACCAAUCGAG	20	4060
  BCL11A-3576	+	UAAGAAUGUCCCCCAAU	17	4061
  BCL11A-3577	−	UAAUCCCCACGCCUGGG	17	4062
  BCL11A-3578	+	UAGAGCUCCAUGUGCAGAAC	20	4063
  BCL11A-3579	−	UAGAGGAAUUUGCCCCAAAC	20	4064
  BCL11A-3580	+	UAUCCACAGCUUUUUCUAAG	20	4065
  BCL11A-3581	−	UCACCUGUGGGCAGUGCCAG	20	4066
  BCL11A-3582	+	UCAUCUCGAUUGGUGAA	17	4067
  BCL11A-3583	+	UCAUCUGGCACUGCCCACAG	20	4068
  BCL11A-3584	+	UCAUCUGUAAGAAUGGCUUC	20	4069
  BCL11A-3585	−	UCAUGACCUCCUCACCU	17	4070
  BCL11A-3586	+	UCCAUGUGCAGAACGAG	17	4071
  BCL11A-3587	+	UCCAUGUGCAGAACGAGGGG	20	4072
  BCL11A-3588	−	UCCCCUCGUUCUGCACA	17	4073
  BCL11A-3589	−	UCCUCCCCUCGUUCUGCACA	20	4074
  BCL11A-3590	−	UCUGCUUAGAAAAAGCU	17	4075
  BCL11A-3591	+	UCUGGCACUGCCCACAG	17	4076
  BCL11A-3592	+	UCUGGCACUGCCCACAGGUG	20	4077
  BCL11A-3593	+	UCUGUAAGAAUGGCUUC	17	4078
  BCL11A-3594	−	UGAAAAAAGCAUCCAAUCCC	20	4079
  BCL11A-3595	−	UGAAGCCAUUCUUACAGAUG	20	4080
  BCL11A-3596	+	UGCCAACCUCCACGGGA	17	4081
  BCL11A-3597	−	UGCCAGAUGAACUUCCCAUU	20	4082
  BCL11A-3598	+	UGCUUUUUUCAUCUCGAUUG	20	4083
  BCL11A-3599	−	UGGAGCUCUAAUCCCCACGC	20	4084
  BCL11A-3600	+	UGGCACUGCCCACAGGU	17	4085
  BCL11A-3601	−	UGGCAUCCAGGUCACGC	17	4086
  BCL11A-3602	+	UGGGGUUUGCCUUGCUUGCG	20	4087
  BCL11A-3603	−	UUAUUUUUAUCGAGCACAAA	20	4088
  BCL11A-3604	+	UUCAUCUCGAUUGGUGA	17	4089
  BCL11A-3605	−	UUGGCAUCCAGGUCACGCCA	20	4090
  BCL11A-3606	+	UUGUGCUCGAUAAAAAU	17	4091
  BCL11A-3607	+	UUUCAUCUCGAUUGGUG	17	4092
  BCL11A-3608	+	UUUCAUCUCGAUUGGUGAAG	20	4093
  BCL11A-3609	+	UUUUCAUCUCGAUUGGUGAA	20	4094
  BCL11A-3610	−	UUUUUAUCGAGCACAAA	17	4095
  BCL11A-3611	+	UUUUUCAUCUCGAUUGGUGA	20	4096
  BCL11A-3612	+	UUUUUUCAUCUCGAUUG	17	4097
  BCL11A-3613	+	UUUUUUCAUCUCGAUUGGUG	20	4098

• Table 5E 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 500 bp 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.
• 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 0-50 bp.
• 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 5E
  			Target	SEQ
  5th Tier	DNA	Targeting	Site	ID
  gRNA Name	Strand	Domain	Length	NO
  BCL11A-3614	+	UCGUCGGACUUGACCGUCAU	20	4099
  BCL11A-3615	+	GUCGUCGGACUUGACCGUCA	20	4100
  BCL11A-3616	+	CGUCGUCGGACUUGACCGUC	20	4101
  BCL11A-3617	+	CGUCGGACUUGACCGUCAUG	20	4102
  BCL11A-3618	−	CCCAUAUUAGUGGUCCGGGC	20	4103
  BCL11A-3619	+	GCGGUCCGACUCGCCGGCCA	20	4104
  BCL11A-3620	+	CUCCGAGGAGUGCUCCGACG	20	4105
  BCL11A-3621	−	CCCCCAUUCGGCGUAGUACC	20	4106
  BCL11A-3622	+	UCUCCGAGGAGUGCUCCGAC	20	4107
  BCL11A-3623	−	CCCGCGGGUUGGUAUCCCUU	20	4108
  BCL11A-3624	+	GCGAGUACACGUUCUCCGUG	20	4109
  BCL11A-3625	−	CCCAUUCGGCGUAGUACCCA	20	4110
  BCL11A-3626	+	CUCCGUGUUGGGCAUCGCGG	20	4111
  BCL11A-3627	+	CCGCGCUUAUGCUUCUCGCC	20	4112
  BCL11A-3628	−	CGACGAAGACUCGGUGGCCG	20	4113
  BCL11A-3629	−	ACCCCCACCGCAUAGAGCGC	20	4114
  BCL11A-3630	+	ACUACGCCGAAUGGGGGUGU	20	4115
  BCL11A-3631	+	CCGGGCCCGGACCACUAAUA	20	4116
  BCL11A-3632	+	CGCGUAGCCGGCGAGCCACU	20	4117
  BCL11A-3633	−	UCGGAGCACUCCUCGGAGAA	20	4118
  BCL11A-3634	−	CGGAGCACUCCUCGGAGAAC	20	4119
  BCL11A-3635	+	UCUCUGGGUACUACGCCGAA	20	4120
  BCL11A-3636	+	UGCCGCAGAACUCGCAUGAC	20	4121
  BCL11A-3637	+	GAUACCAACCCGCGGGGUCA	20	4122
  BCL11A-3638	+	GGAUACCAACCCGCGGGGUC	20	4123
  BCL11A-3639	+	GGGAUACCAACCCGCGGGGU	20	4124
  BCL11A-3640	−	CCCCCACCGCAUAGAGCGCC	20	4125
  BCL11A-3641	+	GGUUGGGGUCGUUCUCGCUC	20	4126
  BCL11A-3642	−	GCACGCCCCAUAUUAGUGGU	20	4127
  BCL11A-3643	−	UAAGCGCAUCAAGCUCGAGA	20	4128
  BCL11A-3644	+	GUUCUCCGAGGAGUGCUCCG	20	4129
  BCL11A-3645	+	UCUCGAGCUUGAUGCGCUUA	20	4130
  BCL11A-3646	−	CUAAGCGCAUCAAGCUCGAG	20	4131
  BCL11A-3647	−	GUCGGAGCACUCCUCGGAGA	20	4132
  BCL11A-3648	−	UGGCCGCGGCUGCUCCCCGG	20	4133
  BCL11A-3649	−	CCCCACCGCAUAGAGCGCCU	20	4134
  BCL11A-3650	+	CCUGAAGGGAUACCAACCCG	20	4135
  BCL11A-3651	−	GCGCUUCUCCACACCGCCCG	20	4136
  BCL11A-3652	−	GCGCCCUGCCCGACGUCAUG	20	4137
  BCL11A-3653	−	AACCCGGCACCAGCGACUUG	20	4138
  BCL11A-3654	+	CUCUGGGUACUACGCCGAAU	20	4139
  BCL11A-3655	+	CCCGUUCUCCGGGAUCAGGU	20	4140
  BCL11A-3656	−	GAACGACCCCAACCUGAUCC	20	4141
  BCL11A-3657	+	ACGCCGAAUGGGGGUGUGUG	20	4142
  BCL11A-3658	+	GUCGCUGGUGCCGGGUUCCG	20	4143
  BCL11A-3659	−	CCCCGGGCGAGUCGGCCUCG	20	4144
  BCL11A-3660	+	CGGUGCACCACCAGGUUGCU	20	4145
  BCL11A-3661	−	GUCCACCACCGAGACAUCAC	20	4146
  BCL11A-3662	−	UUAAUGGCCGCGGCUGCUCC	20	4147
  BCL11A-3663	+	CUCUCUGGGUACUACGCCGA	20	4148
  BCL11A-3664	+	GCGCAAACUCCCGUUCUCCG	20	4149
  BCL11A-3665	+	CCCGGGCCCGGACCACUAAU	20	4150
  BCL11A-3666	+	GCCCCCAGGCGCUCUAUGCG	20	4151
  BCL11A-3667	−	AUCGCCUUUUGCCUCCUCGU	20	4152
  BCL11A-3668	−	CCUCGUCGGAGCACUCCUCG	20	4153
  BCL11A-3669	+	GAGCUUGAUGCGCUUAGAGA	20	4154
  BCL11A-3670	+	CCCCGUUCUCCGGGAUCAGG	20	4155
  BCL11A-3671	−	CGGCCGCGAUGCCCAACACG	20	4156
  BCL11A-3672	+	GCCCCCCGAGGCCGACUCGC	20	4157
  BCL11A-3673	−	CCCGGCCGCGAUGCCCAACA	20	4158
  BCL11A-3674	−	CUCCUCGUCGGAGCACUCCU	20	4159
  BCL11A-3675	+	GUCUCGGUGGUGGACUAAAC	20	4160
  BCL11A-3676	+	CCCCAGGCGCUCUAUGCGGU	20	4161
  BCL11A-3677	+	GGUCGCACAGGUUGCACUUG	20	4162
  BCL11A-3678	+	AGUCGCUGGUGCCGGGUUCC	20	4163
  BCL11A-3679	−	CCCGGUCAAGUCCAAGUCAU	20	4164
  BCL11A-3680	−	AGAACGACCCCAACCUGAUC	20	4165
  BCL11A-3681	+	UCCGUGUUGGGCAUCGCGGC	20	4166
  BCL11A-3682	−	CCUCCUCGUCGGAGCACUCC	20	4167
  BCL11A-3683	−	UCACUUGGACCCCCACCGCA	20	4168
  BCL11A-3684	−	CCCAACCUGAUCCCGGAGAA	20	4169
  BCL11A-3685	−	ACUACGGCUUCGGGCUGAGC	20	4170
  BCL11A-3686	−	UUUGCGCUUCUCCACACCGC	20	4171
  BCL11A-3687	+	AAGUCGCUGGUGCCGGGUUC	20	4172
  BCL11A-3688	−	CCCCAACCUGAUCCCGGAGA	20	4173
  BCL11A-3689	−	AAGACUCGGUGGCCGGCGAG	20	4174
  BCL11A-3690	−	GCGCGGCCACCUGGCCGAGG	20	4175
  BCL11A-3691	−	AAUCGCCUUUUGCCUCCUCG	20	4176
  BCL11A-3692	−	ACGACCCCAACCUGAUCCCG	20	4177
  BCL11A-3693	−	GAUCCCGGAGAACGGGGACG	20	4178
  BCL11A-3694	+	GGGGCAGGUCGAACUCCUUC	20	4179
  BCL11A-3695	−	UGGCUAUGGAGCCUCCCGCC	20	4180
  BCL11A-3696	+	CCCCCAGGCGCUCUAUGCGG	20	4181
  BCL11A-3697	−	GCGGUUGAAUCCAAUGGCUA	20	4182
  BCL11A-3698	−	CUACGGCUUCGGGCUGAGCC	20	4183
  BCL11A-3699	−	ACAGCUCGCGGGGCGCGGUC	20	4184
  BCL11A-3700	−	CCCCCCUGUUUAGUCCACCA	20	4185
  BCL11A-3701	+	CGCAUGACUUGGACUUGACC	20	4186
  BCL11A-3702	−	CACGGAAGUCCCCUGACCCC	20	4187
  BCL11A-3703	−	CCUCCCGCCAUGGAUUUCUC	20	4188
  BCL11A-3704	+	UCUCGGUGGUGGACUAAACA	20	4189
  BCL11A-3705	+	UGAACUUGGCCACCACGGAC	20	4190
  BCL11A-3706	−	CUUCUCUAAGCGCAUCAAGC	20	4191
  BCL11A-3707	+	AGCGCAAACUCCCGUUCUCC	20	4192
  BCL11A-3708	+	UCGGUGGUGGACUAAACAGG	20	4193
  BCL11A-3709	−	CGCCACCACGAGAACAGCUC	20	4194
  BCL11A-3710	−	CUCCCGCCAUGGAUUUCUCU	20	4195
  BCL11A-3711	+	CGAGCUUGAUGCGCUUAGAG	20	4196
  BCL11A-3712	+	AUGCCCUGCAUGACGUCGGG	20	4197
  BCL11A-3713	−	UCUCUAAGCGCAUCAAGCUC	20	4198
  BCL11A-3714	+	GUCCAAGUGAUGUCUCGGUG	20	4199
  BCL11A-3715	+	CCCCCGAGGCCGACUCGCCC	20	4200
  BCL11A-3716	+	CCCCGAGGCCGACUCGCCCG	20	4201
  BCL11A-3717	+	GAAAUUUGAACGUCUUGCCG	20	4202
  BCL11A-3718	+	GUCGCUGCGUCUGCCCUCUU	20	4203
  BCL11A-3719	−	UGGAGGCGGCGCGCCACCAC	20	4204
  BCL11A-3720	+	CUUCUCGAGCUUGAUGCGCU	20	4205
  BCL11A-3721	+	GAAGCGCAAACUCCCGUUCU	20	4206
  BCL11A-3722	−	GAGAGAGGCUUCCGGCCUGG	20	4207
  BCL11A-3723	−	UCCCCGGGCGAGUCGGCCUC	20	4208
  BCL11A-3724	+	CAAGUCGCUGGUGCCGGGUU	20	4209
  BCL11A-3725	−	CAUAGAGCGCCUGGGGGCGG	20	4210
  BCL11A-3726	+	CUCGGUGGUGGACUAAACAG	20	4211
  BCL11A-3727	+	CCCCCCGAGGCCGACUCGCC	20	4212
  BCL11A-3728	−	GGUUUCUCUUGCAACACGCA	20	4213
  BCL11A-3729	+	ACUUGGACUUGACCGGGGGC	20	4214
  BCL11A-3730	−	UGAUCCCGGAGAACGGGGAC	20	4215
  BCL11A-3731	+	UGUCUGGAGUCUCCGAAGCU	20	4216
  BCL11A-3732	−	AUGGAUUUCUCUAGGAGACU	20	4217
  BCL11A-3733	−	UGCGGUUGAAUCCAAUGGCU	20	4218
  BCL11A-3734	−	CUCCCCGGGCGAGUCGGCCU	20	4219
  BCL11A-3735	−	CCUGAUCCCGGAGAACGGGG	20	4220
  BCL11A-3736	+	UGUCUCGGUGGUGGACUAAA	20	4221
  BCL11A-3737	+	CGGUGGUGGACUAAACAGGG	20	4222
  BCL11A-3738	+	UGCCCACCAAGUCGCUGGUG	20	4223
  BCL11A-3739	−	CGUGGUGGCCAAGUUCAAGA	20	4224
  BCL11A-3740	−	CAUCACCCGAGUGCCUUUGA	20	4225
  BCL11A-3741	−	GCGGCAAGACGUUCAAAUUU	20	4226
  BCL11A-3742	+	AAGGGCUCUCGAGCUUCCAU	20	4227
  BCL11A-3743	+	GUCUGGAGUCUCCGAAGCUA	20	4228
  BCL11A-3744	−	CCCCGGCCGCGAUGCCCAAC	20	4229
  BCL11A-3745	+	CUGUCAAAGGCACUCGGGUG	20	4230
  BCL11A-3746	+	CUUGGACUUGACCGGGGGCU	20	4231
  BCL11A-3747	+	GACUUGGACUUGACCGGGGG	20	4232
  BCL11A-3748	+	UGCGUCUGCCCUCUUUUGAG	20	4233
  BCL11A-3749	+	GGAGGCAAAAGGCGAUUGUC	20	4234
  BCL11A-3750	−	GCAACACGCACAGAACACUC	20	4235
  BCL11A-3751	+	GCAGUAACCUUUGCAUAGGG	20	4236
  BCL11A-3752	−	UGGUGCACCGGCGCAGCCAC	20	4237
  BCL11A-3753	−	UGGUGGCCAAGUUCAAGAGC	20	4238
  BCL11A-3754	−	GCAUAAGCGCGGCCACCUGG	20	4239
  BCL11A-3755	+	UUGCAUAGGGCUGGGCCGGC	20	4240
  BCL11A-3756	−	CCAACCUGAUCCCGGAGAAC	20	4241
  BCL11A-3757	−	AGAUGUGUGGCAGUUUUCGG	20	4242
  BCL11A-3758	−	CAGUUUUCGGAUGGAAGCUC	20	4243
  BCL11A-3759	−	GCUCCCCGGGCGAGUCGGCC	20	4244
  BCL11A-3760	−	GGGUGGACUACGGCUUCGGG	20	4245
  BCL11A-3761	−	UAUCCCUUCAGGACUAGGUG	20	4246
  BCL11A-3762	−	AUCUCGGGGCGCAGCGGCAC	20	4247
  BCL11A-3763	+	CGCUCUUGAACUUGGCCACC	20	4248
  BCL11A-3764	−	GCACCGGCGCAGCCACACGG	20	4249
  BCL11A-3765	+	GCUUCUCGCCCAGGACCUGG	20	4250
  BCL11A-3766	−	UCCCGGAGAACGGGGACGAG	20	4251
  BCL11A-3767	+	CAGCACCCUGUCAAAGGCAC	20	4252
  BCL11A-3768	+	CAUUCUGCACCUAGUCCUGA	20	4253
  BCL11A-3769	−	CUUUAACCUGCUAAGAAUAC	20	4254
  BCL11A-3770	−	GUCUCUCCACCGCCAGCUCC	20	4255
  BCL11A-3771	−	UCUCUCCACCGCCAGCUCCC	20	4256
  BCL11A-3772	+	UGCUUCUCGCCCAGGACCUG	20	4257
  BCL11A-3773	+	GCGCCGCCUCCAGGCUCAGC	20	4258
  BCL11A-3774	+	AGAUCCCUCCGUCCAGCUCC	20	4259
  BCL11A-3775	−	CGAGAGGGUGGACUACGGCU	20	4260
  BCL11A-3776	+	CGUCCAGCUCCCCGGGCGGU	20	4261
  BCL11A-3777	+	CCAGCUCUCUAAGUCUCCUA	20	4262
  BCL11A-3778	+	UCGCAUGACUUGGACUUGAC	20	4263
  BCL11A-3779	+	GCACCAUGCCCUGCAUGACG	20	4264
  BCL11A-3780	+	AAGGCGAUUGUCUGGAGUCU	20	4265
  BCL11A-3781	+	GCCUGGAGGCCGCGUAGCCG	20	4266
  BCL11A-3782	−	GCGGCCACCUGGCCGAGGCC	20	4267
  BCL11A-3783	−	AGAAUACCAGGAUCAGUAUC	20	4268
  BCL11A-3784	−	GAUGUGUGGCAGUUUUCGGA	20	4269
  BCL11A-3785	−	UCUCCACACCGCCCGGGGAG	20	4270
  BCL11A-3786	−	CCUGGAGGCGGCGCGCCACC	20	4271
  BCL11A-3787	+	CUGGUAUUCUUAGCAGGUUA	20	4272
  BCL11A-3788	+	UAGAGAAGGGGCUCAGCGAG	20	4273
  BCL11A-3789	+	GAGUGUUCUGUGCGUGUUGC	20	4274
  BCL11A-3790	−	AAUAACCCCUUUAACCUGCU	20	4275
  BCL11A-3791	+	AAAGCGCCCUUCUGCCAGGC	20	4276
  BCL11A-3792	+	GUCCAGCUCCCCGGGCGGUG	20	4277
  BCL11A-3793	+	AAGGGCGGCUUGCUACCUGG	20	4278
  BCL11A-3794	+	GAAAGCGCCCUUCUGCCAGG	20	4279
  BCL11A-3795	+	AGGGCGGCUUGCUACCUGGC	20	4280
  BCL11A-3796	−	CGCGGGGCGCGGUCGUGGGC	20	4281
  BCL11A-3797	−	GCGAGGCCUUCCACCAGGUC	20	4282
  BCL11A-3798	+	ACUUCCCGUGCCGCUGCGCC	20	4283
  BCL11A-3799	−	GCACAGAACACUCAUGGAUU	20	4284
  BCL11A-3800	+	CCAGCUCCCCGGGCGGUGUG	20	4285
  BCL11A-3801	−	ACCGCCCGGGGAGCUGGACG	20	4286
  BCL11A-3802	+	UGGUUGCAGUAACCUUUGCA	20	4287
  BCL11A-3803	−	AGGAGACUUAGAGAGCUGGC	20	4288
  BCL11A-3804	−	ACCGGCGCAGCCACACGGGC	20	4289
  BCL11A-3805	+	ACAUUCUGCACCUAGUCCUG	20	4290
  BCL11A-3806	+	GUGUUCUGUGCGUGUUGCAA	20	4291
  BCL11A-3807	−	UGGCCCUGGCCACCCAUCAC	20	4292
  BCL11A-3808	+	UGCAUAGGGCUGGGCCGGCC	20	4293
  BCL11A-3809	−	AAUACCAGGAUCAGUAUCGA	20	4294
  BCL11A-3810	+	UCCUGAAGGGAUACCAACCC	20	4295
  BCL11A-3811	+	CUCCUAGAGAAAUCCAUGGC	20	4296
  BCL11A-3812	+	UGGCGGUGGAGAGACCGUCG	20	4297
  BCL11A-3813	−	GGAUUUCUCUAGGAGACUUA	20	4298
  BCL11A-3814	+	CUCGCAUGACUUGGACUUGA	20	4299
  BCL11A-3815	−	GAUCUCGGGGCGCAGCGGCA	20	4300
  BCL11A-3816	+	GGUGGUGGACUAAACAGGGG	20	4301
  BCL11A-3817	+	AGGCCUCGCUGAAGUGCUGC	20	4302
  BCL11A-3818	+	CCACCAGGUUGCUCUGAAAU	20	4303
  BCL11A-3819	−	ACCGCAUAGAGCGCCUGGGG	20	4304
  BCL11A-3820	−	CCAGCAAGCUGAAGCGCCAC	20	4305
  BCL11A-3821	+	GGCCUCGCUGAAGUGCUGCA	20	4306
  BCL11A-3822	−	CGUGCACCCAGGCCAGCAAG	20	4307
  BCL11A-3823	+	GGCGGGAGGCUCCAUAGCCA	20	4308
  BCL11A-3824	+	AGGAGGCAAAAGGCGAUUGU	20	4309
  BCL11A-3825	−	AAAGAUCCCUUCCUUAGCUU	20	4310
  BCL11A-3826	+	GGAGUCUCCGAAGCUAAGGA	20	4311
  BCL11A-3827	+	GCGCUUAGAGAAGGGGCUCA	20	4312
  BCL11A-3828	+	CAGCUUUUUGGACAGGCCCC	20	4313
  BCL11A-3829	+	GCACUCGGGUGAUGGGUGGC	20	4314
  BCL11A-3830	+	CACGCCCACGACCGCGCCCC	20	4315
  BCL11A-3831	+	AAGUUGUACAUGUGUAGCUG	20	4316
  BCL11A-3832	−	AGUCCGUGGUGGCCAAGUUC	20	4317
  BCL11A-3833	−	CCCGGAGAACGGGGACGAGG	20	4318
  BCL11A-3834	−	CGGGCAGGCCCAGCUCAAAA	20	4319
  BCL11A-3835	+	UGGUAUUCUUAGCAGGUUAA	20	4320
  BCL11A-3836	+	UUGUCUGCAAUAUGAAUCCC	20	4321
  BCL11A-3837	+	GUCUCCUAGAGAAAUCCAUG	20	4322
  BCL11A-3838	+	UGGACUUGACCGGGGGCUGG	20	4323
  BCL11A-3839	+	UGGAGUCUCCGAAGCUAAGG	20	4324
  BCL11A-3840	+	UGAGCUGGGCCUGCCCGGGC	20	4325
  BCL11A-3841	−	CAAAGAUCCCUUCCUUAGCU	20	4326
  BCL11A-3842	+	UGCCACACAUCUUGAGCUCU	20	4327
  BCL11A-3843	−	CCGCCCGGGGAGCUGGACGG	20	4328
  BCL11A-3844	+	AGAGAAGGGGCUCAGCGAGC	20	4329
  BCL11A-3845	−	GGAGACUUAGAGAGCUGGCA	20	4330
  BCL11A-3846	+	GAAUCCCAUGGAGAGGUGGC	20	4331
  BCL11A-3847	+	CGCUGAAGUGCUGCAUGGAG	20	4332
  BCL11A-3848	+	AGGACAUUCUGCACCUAGUC	20	4333
  BCL11A-3849	+	AAUCCCAUGGAGAGGUGGCU	20	4334
  BCL11A-3850	+	UGAGCUCUCUGGGUACUACG	20	4335
  BCL11A-3851	−	GGGCCACAGGGACACUUGCG	20	4336
  BCL11A-3852	−	UAGGAGACUUAGAGAGCUGG	20	4337
  BCL11A-3853	−	CCUUUGACAGGGUGCUGCGG	20	4338
  BCL11A-3854	−	UGGCCGAGGCCGAGGGCCAC	20	4339
  BCL11A-3855	+	GGAAGGGAUCUUUGAGCUGC	20	4340
  BCL11A-3856	+	UCUAAGUAGAUUCUUAAUCC	20	4341
  BCL11A-3857	−	GGGGCGCAGCGGCACGGGAA	20	4342
  BCL11A-3858	−	CUGGCCGAGGCCGAGGGCCA	20	4343
  BCL11A-3859	−	CUCAAGAUGUGUGGCAGUUU	20	4344
  BCL11A-3860	+	CGAAGCUAAGGAAGGGAUCU	20	4345
  BCL11A-3861	+	UGCCAGCUCUCUAAGUCUCC	20	4346
  BCL11A-3862	+	UCUCCUAGAGAAAUCCAUGG	20	4347
  BCL11A-3863	−	GCCACCACGAGAACAGCUCG	20	4348
  BCL11A-3864	+	UCUGCAAUAUGAAUCCCAUG	20	4349
  BCL11A-3865	−	CAGCUCCAUGCAGCACUUCA	20	4350
  BCL11A-3866	−	GCCUGUCCAAAAAGCUGCUG	20	4351
  BCL11A-3867	−	UAAGAAUACCAGGAUCAGUA	20	4352
  BCL11A-3868	−	GGAUCUCGGGGCGCAGCGGC	20	4353
  BCL11A-3869	−	GGCAGUUUUCGGAUGGAAGC	20	4354
  BCL11A-3870	−	CGGUCGUGGGCGUGGGCGAC	20	4355
  BCL11A-3871	+	GCAUCGCGGCCGGGGGCAGG	20	4356
  BCL11A-3872	−	AAUCUACUUAGAAAGCGAAC	20	4357
  BCL11A-3873	+	AAGGGGUUAUUGUCUGCAAU	20	4358
  BCL11A-3874	+	GGACUUGACCGGGGGCUGGG	20	4359
  BCL11A-3875	−	UCAUGGAUUAAGAAUCUACU	20	4360
  BCL11A-3876	−	AGAGGCUUCCGGCCUGGCAG	20	4361
  BCL11A-3877	−	GGCCUUCCACCAGGUCCUGG	20	4362
  BCL11A-3878	+	UGGCGCUUCAGCUUGCUGGC	20	4363
  BCL11A-3879	−	CCGCAUAGAGCGCCUGGGGG	20	4364
  BCL11A-3880	+	GGACCUGGUGGAAGGCCUCG	20	4365
  BCL11A-3881	−	CCUUCCACCAGGUCCUGGGC	20	4366
  BCL11A-3882	+	UGUCUGCAAUAUGAAUCCCA	20	4367
  BCL11A-3883	−	GGAGCUGGACGGAGGGAUCU	20	4368
  BCL11A-3884	+	GACUUGACCGGGGGCUGGGA	20	4369
  BCL11A-3885	−	UCCUUCCCAGCCACCUCUCC	20	4370
  BCL11A-3886	+	CUCUUUUGAGCUGGGCCUGC	20	4371
  BCL11A-3887	−	UGCGCUUCUCCACACCGCCC	20	4372
  BCL11A-3888	+	GCAAGAGAAACCAUGCACUG	20	4373
  BCL11A-3889	−	GGGAGCUGGACGGAGGGAUC	20	4374
  BCL11A-3890	+	GUUCCGGGGAGCUGGCGGUG	20	4375
  BCL11A-3891	+	UGAAUCCCAUGGAGAGGUGG	20	4376
  BCL11A-3892	+	CGGGUUCCGGGGAGCUGGCG	20	4377
  BCL11A-3893	+	GUGGACUAAACAGGGGGGGA	20	4378
  BCL11A-3894	+	GGCUGCCCAGCAGCAGCUUU	20	4379
  BCL11A-3895	+	GAAGGGAUCUUUGAGCUGCC	20	4380
  BCL11A-3896	−	CCUUCCCAGCCACCUCUCCA	20	4381
  BCL11A-3897	−	GCGCAGCGGCACGGGAAGUG	20	4382
  BCL11A-3898	+	GGGUUCCGGGGAGCUGGCGG	20	4383
  BCL11A-3899	+	UCCUCCUCGUCCCCGUUCUC	20	4384
  BCL11A-3900	−	GCAGCGGCACGGGAAGUGGA	20	4385
  BCL11A-3901	−	UGCUGGGCAGCCCCAGCUCG	20	4386
  BCL11A-3902	−	GGGCGCAGCGGCACGGGAAG	20	4387
  BCL11A-3903	−	ACACCGCCCGGGGAGCUGGA	20	4388
  BCL11A-3904	+	CCCAUGGAGAGGUGGCUGGG	20	4389
  BCL11A-3905	+	UUCCUCCUCGUCCCCGUUCU	20	4390
  BCL11A-3906	−	AUCUACUUAGAAAGCGAACA	20	4391
  BCL11A-3907	−	CCCGGGCAGGCCCAGCUCAA	20	4392
  BCL11A-3908	−	CACACCGCCCGGGGAGCUGG	20	4393
  BCL11A-3909	+	ACUAAACAGGGGGGGAGUGG	20	4394
  BCL11A-3910	+	GACCGGGGGCUGGGAGGGAG	20	4395
  BCL11A-3911	+	GGGCCGGCCUGGGGACAGCG	20	4396
  BCL11A-3912	+	GCAUAGGGCUGGGCCGGCCU	20	4397
  BCL11A-3913	−	AUUAAGAAUCUACUUAGAAA	20	4398
  BCL11A-3914	+	CUAAACAGGGGGGGAGUGGG	20	4399
  BCL11A-3915	+	UUGACCGGGGGCUGGGAGGG	20	4400
  BCL11A-3916	−	CGCGGUCGUGGGCGUGGGCG	20	4401
  BCL11A-3917	+	GAGGGAGGGGGGGCGUCGCC	20	4402
  BCL11A-3918	−	GGAGAACGGGGACGAGGAGG	20	4403
  BCL11A-3919	+	CUUGACCGGGGGCUGGGAGG	20	4404
  BCL11A-3920	+	GGAGGGAGGGGGGGCGUCGC	20	4405
  BCL11A-3921	+	ACCGGGGGCUGGGAGGGAGG	20	4406
  BCL11A-3922	−	CGCAGCGGCACGGGAAGUGG	20	4407
  BCL11A-3923	+	GCGGAUUGCAGAGGAGGGAG	20	4408
  BCL11A-3924	+	GGAGGGGGGGCGUCGCCAGG	20	4409
  BCL11A-3925	+	GGCGGAUUGCAGAGGAGGGA	20	4410
  BCL11A-3926	+	GAGGGGCGGAUUGCAGAGGA	20	4411
  BCL11A-3927	+	GGGGCGGAUUGCAGAGGAGG	20	4412
  BCL11A-3928	−	GAGGAGCUGACGGAGAGCGA	20	4413
  BCL11A-3929	+	UCCGAAAACUGCCACACAUC	20	4414
  BCL11A-3930	+	CGGAUUGCAGAGGAGGGAGG	20	4415
  BCL11A-3931	+	GGAGGGGCGGAUUGCAGAGG	20	4416
  BCL11A-3932	+	GGGCGGAUUGCAGAGGAGGG	20	4417
  BCL11A-3933	+	AGGAGGGGCGGAUUGCAGAG	20	4418
  BCL11A-3934	−	AGAACGGGGACGAGGAGGAA	20	4419
  BCL11A-3935	+	GAGGGAGGAGGGGCGGAUUG	20	4420
  BCL11A-3936	−	UUGCGCUUCUCCACACCGCC	20	4421
  BCL11A-3937	−	AGCUGACGGAGAGCGAGAGG	20	4422
  BCL11A-3938	−	AGGAGGAGCUGACGGAGAGC	20	4423
  BCL11A-3939	+	GGGGCUGGGAGGGAGGAGGG	20	4424
  BCL11A-3940	+	GGGAGGAGGGGCGGAUUGCA	20	4425
  BCL11A-3941	+	CCGUGUUGGGCAUCGCGGCC	20	4426
  BCL11A-3942	−	GAACGGGGACGAGGAGGAAG	20	4427
  BCL11A-3943	+	GGAGGAGGGGCGGAUUGCAG	20	4428
  BCL11A-3944	−	GGAGGAGGAGCUGACGGAGA	20	4429
  BCL11A-3945	−	ACGGGGACGAGGAGGAAGAG	20	4430
  BCL11A-3946	−	AGGAGGAGGAGGAGCUGACG	20	4431
  BCL11A-3947	−	ACGACGAGGAAGAGGAAGAA	20	4432
  BCL11A-3948	−	ACGAGGAAGAGGAAGAAGAG	20	4433
  BCL11A-3949	−	AGGAGGAAGAGGAGGACGAC	20	4434
  BCL11A-3950	−	AAGAGGAGGACGACGAGGAA	20	4435
  BCL11A-3951	−	AGAGGAGGAGGAGGAGCUGA	20	4436
  BCL11A-3952	−	GGAGGAAGAGGAGGACGACG	20	4437
  BCL11A-3953	−	CGAGGAGGAAGAGGAGGACG	20	4438
  BCL11A-3954	−	CGAGGAAGAGGAAGAAGAGG	20	4439
  BCL11A-3955	−	AAGAGGAGGAGGAGGAGCUG	20	4440
  BCL11A-3956	−	CGACGAGGAAGAGGAAGAAG	20	4441
  BCL11A-3957	−	GGAGGACGACGAGGAAGAGG	20	4442
  BCL11A-3958	−	AGAGGAGGACGACGAGGAAG	20	4443
  BCL11A-3959	−	GGACGACGAGGAAGAGGAAG	20	4444
  BCL11A-3960	−	GGAAGAGGAGGACGACGAGG	20	4445
  BCL11A-3961	−	AGGAAGAAGAGGAGGAAGAG	20	4446
  BCL11A-3962	−	AAGAGGAAGAAGAGGAGGAA	20	4447
  BCL11A-3963	−	GGAAGAGGAAGAAGAGGAGG	20	4448
  BCL11A-3964	−	AAGAAGAGGAGGAAGAGGAG	20	4449
  BCL11A-3965	−	AAGAGGAGGAAGAGGAGGAG	20	4450
  BCL11A-3966	−	AGAGGAAGAAGAGGAGGAAG	20	4451
  BCL11A-3967	−	GGAAGAAGAGGAGGAAGAGG	20	4452
  BCL11A-3968	−	AGAAGAGGAGGAAGAGGAGG	20	4453
  BCL11A-3969	−	AGAGGAGGAAGAGGAGGAGG	20	4454
  BCL11A-3970	+	UCGGACUUGACCGUCAU	17	4455
  BCL11A-3971	+	GUCGGACUUGACCGUCA	17	4456
  BCL11A-3972	+	CGUCGGACUUGACCGUC	17	4457
  BCL11A-3973	+	CGGACUUGACCGUCAUG	17	4458
  BCL11A-3974	−	AUAUUAGUGGUCCGGGC	17	4459
  BCL11A-3975	+	GUCCGACUCGCCGGCCA	17	4460
  BCL11A-3976	+	CGAGGAGUGCUCCGACG	17	4461
  BCL11A-3977	−	CCAUUCGGCGUAGUACC	17	4462
  BCL11A-3978	+	CCGAGGAGUGCUCCGAC	17	4463
  BCL11A-3979	−	GCGGGUUGGUAUCCCUU	17	4464
  BCL11A-3980	+	AGUACACGUUCUCCGUG	17	4465
  BCL11A-3981	−	AUUCGGCGUAGUACCCA	17	4466
  BCL11A-3982	+	CGUGUUGGGCAUCGCGG	17	4467
  BCL11A-3983	+	CGCUUAUGCUUCUCGCC	17	4468
  BCL11A-3984	−	CGAAGACUCGGUGGCCG	17	4469
  BCL11A-3985	−	CCCACCGCAUAGAGCGC	17	4470
  BCL11A-3986	+	ACGCCGAAUGGGGGUGU	17	4471
  BCL11A-3987	+	GGCCCGGACCACUAAUA	17	4472
  BCL11A-3988	+	GUAGCCGGCGAGCCACU	17	4473
  BCL11A-3989	−	GAGCACUCCUCGGAGAA	17	4474
  BCL11A-3990	−	AGCACUCCUCGGAGAAC	17	4475
  BCL11A-3991	+	CUGGGUACUACGCCGAA	17	4476
  BCL11A-3992	+	CGCAGAACUCGCAUGAC	17	4477
  BCL11A-3993	+	ACCAACCCGCGGGGUCA	17	4478
  BCL11A-3994	+	UACCAACCCGCGGGGUC	17	4479
  BCL11A-3995	+	AUACCAACCCGCGGGGU	17	4480
  BCL11A-3996	−	CCACCGCAUAGAGCGCC	17	4481
  BCL11A-3997	+	UGGGGUCGUUCUCGCUC	17	4482
  BCL11A-3998	−	CGCCCCAUAUUAGUGGU	17	4483
  BCL11A-3999	−	GCGCAUCAAGCUCGAGA	17	4484
  BCL11A-4000	+	CUCCGAGGAGUGCUCCG	17	4485
  BCL11A-4001	+	CGAGCUUGAUGCGCUUA	17	4486
  BCL11A-4002	−	AGCGCAUCAAGCUCGAG	17	4487
  BCL11A-4003	−	GGAGCACUCCUCGGAGA	17	4488
  BCL11A-4004	−	CCGCGGCUGCUCCCCGG	17	4489
  BCL11A-4005	−	CACCGCAUAGAGCGCCU	17	4490
  BCL11A-4006	+	GAAGGGAUACCAACCCG	17	4491
  BCL11A-4007	−	CUUCUCCACACCGCCCG	17	4492
  BCL11A-4008	−	CCCUGCCCGACGUCAUG	17	4493
  BCL11A-4009	−	CCGGCACCAGCGACUUG	17	4494
  BCL11A-4010	+	UGGGUACUACGCCGAAU	17	4495
  BCL11A-4011	+	GUUCUCCGGGAUCAGGU	17	4496
  BCL11A-4012	−	CGACCCCAACCUGAUCC	17	4497
  BCL11A-4013	+	CCGAAUGGGGGUGUGUG	17	4498
  BCL11A-4014	+	GCUGGUGCCGGGUUCCG	17	4499
  BCL11A-4015	−	CGGGCGAGUCGGCCUCG	17	4500
  BCL11A-4016	+	UGCACCACCAGGUUGCU	17	4501
  BCL11A-4017	−	CACCACCGAGACAUCAC	17	4502
  BCL11A-4018	−	AUGGCCGCGGCUGCUCC	17	4503
  BCL11A-4019	+	UCUGGGUACUACGCCGA	17	4504
  BCL11A-4020	+	CAAACUCCCGUUCUCCG	17	4505
  BCL11A-4021	+	GGGCCCGGACCACUAAU	17	4506
  BCL11A-4022	+	CCCAGGCGCUCUAUGCG	17	4507
  BCL11A-4023	−	GCCUUUUGCCUCCUCGU	17	4508
  BCL11A-4024	−	CGUCGGAGCACUCCUCG	17	4509
  BCL11A-4025	+	CUUGAUGCGCUUAGAGA	17	4510
  BCL11A-4026	+	CGUUCUCCGGGAUCAGG	17	4511
  BCL11A-4027	−	CCGCGAUGCCCAACACG	17	4512
  BCL11A-4028	+	CCCCGAGGCCGACUCGC	17	4513
  BCL11A-4029	−	GGCCGCGAUGCCCAACA	17	4514
  BCL11A-4030	−	CUCGUCGGAGCACUCCU	17	4515
  BCL11A-4031	+	UCGGUGGUGGACUAAAC	17	4516
  BCL11A-4032	+	CAGGCGCUCUAUGCGGU	17	4517
  BCL11A-4033	+	CGCACAGGUUGCACUUG	17	4518
  BCL11A-4034	+	CGCUGGUGCCGGGUUCC	17	4519
  BCL11A-4035	−	GGUCAAGUCCAAGUCAU	17	4520
  BCL11A-4036	−	ACGACCCCAACCUGAUC	17	4521
  BCL11A-4037	+	GUGUUGGGCAUCGCGGC	17	4522
  BCL11A-4038	−	CCUCGUCGGAGCACUCC	17	4523
  BCL11A-4039	−	CUUGGACCCCCACCGCA	17	4524
  BCL11A-4040	−	AACCUGAUCCCGGAGAA	17	4525
  BCL11A-4041	−	ACGGCUUCGGGCUGAGC	17	4526
  BCL11A-4042	−	GCGCUUCUCCACACCGC	17	4527
  BCL11A-4043	+	UCGCUGGUGCCGGGUUC	17	4528
  BCL11A-4044	−	CAACCUGAUCCCGGAGA	17	4529
  BCL11A-4045	−	ACUCGGUGGCCGGCGAG	17	4530
  BCL11A-4046	−	CGGCCACCUGGCCGAGG	17	4531
  BCL11A-4047	−	CGCCUUUUGCCUCCUCG	17	4532
  BCL11A-4048	−	ACCCCAACCUGAUCCCG	17	4533
  BCL11A-4049	−	CCCGGAGAACGGGGACG	17	4534
  BCL11A-4050	+	GCAGGUCGAACUCCUUC	17	4535
  BCL11A-4051	−	CUAUGGAGCCUCCCGCC	17	4536
  BCL11A-4052	+	CCAGGCGCUCUAUGCGG	17	4537
  BCL11A-4053	−	GUUGAAUCCAAUGGCUA	17	4538
  BCL11A-4054	−	CGGCUUCGGGCUGAGCC	17	4539
  BCL11A-4055	−	GCUCGCGGGGCGCGGUC	17	4540
  BCL11A-4056	−	CCCUGUUUAGUCCACCA	17	4541
  BCL11A-4057	+	AUGACUUGGACUUGACC	17	4542
  BCL11A-4058	−	GGAAGUCCCCUGACCCC	17	4543
  BCL11A-4059	−	CCCGCCAUGGAUUUCUC	17	4544
  BCL11A-4060	+	CGGUGGUGGACUAAACA	17	4545
  BCL11A-4061	+	ACUUGGCCACCACGGAC	17	4546
  BCL11A-4062	−	CUCUAAGCGCAUCAAGC	17	4547
  BCL11A-4063	+	GCAAACUCCCGUUCUCC	17	4548
  BCL11A-4064	+	GUGGUGGACUAAACAGG	17	4549
  BCL11A-4065	−	CACCACGAGAACAGCUC	17	4550
  BCL11A-4066	−	CCGCCAUGGAUUUCUCU	17	4551
  BCL11A-4067	+	GCUUGAUGCGCUUAGAG	17	4552
  BCL11A-4068	+	CCCUGCAUGACGUCGGG	17	4553
  BCL11A-4069	−	CUAAGCGCAUCAAGCUC	17	4554
  BCL11A-4070	+	CAAGUGAUGUCUCGGUG	17	4555
  BCL11A-4071	+	CCGAGGCCGACUCGCCC	17	4556
  BCL11A-4072	+	CGAGGCCGACUCGCCCG	17	4557
  BCL11A-4073	+	AUUUGAACGUCUUGCCG	17	4558
  BCL11A-4074	+	GCUGCGUCUGCCCUCUU	17	4559
  BCL11A-4075	−	AGGCGGCGCGCCACCAC	17	4560
  BCL11A-4076	+	CUCGAGCUUGAUGCGCU	17	4561
  BCL11A-4077	+	GCGCAAACUCCCGUUCU	17	4562
  BCL11A-4078	−	AGAGGCUUCCGGCCUGG	17	4563
  BCL11A-4079	−	CCGGGCGAGUCGGCCUC	17	4564
  BCL11A-4080	+	GUCGCUGGUGCCGGGUU	17	4565
  BCL11A-4081	−	AGAGCGCCUGGGGGCGG	17	4566
  BCL11A-4082	+	GGUGGUGGACUAAACAG	17	4567
  BCL11A-4083	+	CCCGAGGCCGACUCGCC	17	4568
  BCL11A-4084	−	UUCUCUUGCAACACGCA	17	4569
  BCL11A-4085	+	UGGACUUGACCGGGGGC	17	4570
  BCL11A-4086	−	UCCCGGAGAACGGGGAC	17	4571
  BCL11A-4087	+	CUGGAGUCUCCGAAGCU	17	4572
  BCL11A-4088	−	GAUUUCUCUAGGAGACU	17	4573
  BCL11A-4089	−	GGUUGAAUCCAAUGGCU	17	4574
  BCL11A-4090	−	CCCGGGCGAGUCGGCCU	17	4575
  BCL11A-4091	−	GAUCCCGGAGAACGGGG	17	4576
  BCL11A-4092	+	CUCGGUGGUGGACUAAA	17	4577
  BCL11A-4093	+	UGGUGGACUAAACAGGG	17	4578
  BCL11A-4094	+	CCACCAAGUCGCUGGUG	17	4579
  BCL11A-4095	−	GGUGGCCAAGUUCAAGA	17	4580
  BCL11A-4096	−	CACCCGAGUGCCUUUGA	17	4581
  BCL11A-4097	−	GCAAGACGUUCAAAUUU	17	4582
  BCL11A-4098	+	GGCUCUCGAGCUUCCAU	17	4583
  BCL11A-4099	+	UGGAGUCUCCGAAGCUA	17	4584
  BCL11A-4100	−	CGGCCGCGAUGCCCAAC	17	4585
  BCL11A-4101	+	UCAAAGGCACUCGGGUG	17	4586
  BCL11A-4102	+	GGACUUGACCGGGGGCU	17	4587
  BCL11A-4103	+	UUGGACUUGACCGGGGG	17	4588
  BCL11A-4104	+	GUCUGCCCUCUUUUGAG	17	4589
  BCL11A-4105	+	GGCAAAAGGCGAUUGUC	17	4590
  BCL11A-4106	−	ACACGCACAGAACACUC	17	4591
  BCL11A-4107	+	GUAACCUUUGCAUAGGG	17	4592
  BCL11A-4108	−	UGCACCGGCGCAGCCAC	17	4593
  BCL11A-4109	−	UGGCCAAGUUCAAGAGC	17	4594
  BCL11A-4110	−	UAAGCGCGGCCACCUGG	17	4595
  BCL11A-4111	+	CAUAGGGCUGGGCCGGC	17	4596
  BCL11A-4112	−	ACCUGAUCCCGGAGAAC	17	4597
  BCL11A-4113	−	UGUGUGGCAGUUUUCGG	17	4598
  BCL11A-4114	−	UUUUCGGAUGGAAGCUC	17	4599
  BCL11A-4115	−	CCCCGGGCGAGUCGGCC	17	4600
  BCL11A-4116	−	UGGACUACGGCUUCGGG	17	4601
  BCL11A-4117	−	CCCUUCAGGACUAGGUG	17	4602
  BCL11A-4118	−	UCGGGGCGCAGCGGCAC	17	4603
  BCL11A-4119	+	UCUUGAACUUGGCCACC	17	4604
  BCL11A-4120	−	CCGGCGCAGCCACACGG	17	4605
  BCL11A-4121	+	UCUCGCCCAGGACCUGG	17	4606
  BCL11A-4122	−	CGGAGAACGGGGACGAG	17	4607
  BCL11A-4123	+	CACCCUGUCAAAGGCAC	17	4608
  BCL11A-4124	+	UCUGCACCUAGUCCUGA	17	4609
  BCL11A-4125	−	UAACCUGCUAAGAAUAC	17	4610
  BCL11A-4126	−	UCUCCACCGCCAGCUCC	17	4611
  BCL11A-4127	−	CUCCACCGCCAGCUCCC	17	4612
  BCL11A-4128	+	UUCUCGCCCAGGACCUG	17	4613
  BCL11A-4129	+	CCGCCUCCAGGCUCAGC	17	4614
  BCL11A-4130	+	UCCCUCCGUCCAGCUCC	17	4615
  BCL11A-4131	−	GAGGGUGGACUACGGCU	17	4616
  BCL11A-4132	+	CCAGCUCCCCGGGCGGU	17	4617
  BCL11A-4133	+	GCUCUCUAAGUCUCCUA	17	4618
  BCL11A-4134	+	CAUGACUUGGACUUGAC	17	4619
  BCL11A-4135	+	CCAUGCCCUGCAUGACG	17	4620
  BCL11A-4136	+	GCGAUUGUCUGGAGUCU	17	4621
  BCL11A-4137	+	UGGAGGCCGCGUAGCCG	17	4622
  BCL11A-4138	−	GCCACCUGGCCGAGGCC	17	4623
  BCL11A-4139	−	AUACCAGGAUCAGUAUC	17	4624
  BCL11A-4140	−	GUGUGGCAGUUUUCGGA	17	4625
  BCL11A-4141	−	CCACACCGCCCGGGGAG	17	4626
  BCL11A-4142	−	GGAGGCGGCGCGCCACC	17	4627
  BCL11A-4143	+	GUAUUCUUAGCAGGUUA	17	4628
  BCL11A-4144	+	AGAAGGGGCUCAGCGAG	17	4629
  BCL11A-4145	+	UGUUCUGUGCGUGUUGC	17	4630
  BCL11A-4146	−	AACCCCUUUAACCUGCU	17	4631
  BCL11A-4147	+	GCGCCCUUCUGCCAGGC	17	4632
  BCL11A-4148	+	CAGCUCCCCGGGCGGUG	17	4633
  BCL11A-4149	+	GGCGGCUUGCUACCUGG	17	4634
  BCL11A-4150	+	AGCGCCCUUCUGCCAGG	17	4635
  BCL11A-4151	+	GCGGCUUGCUACCUGGC	17	4636
  BCL11A-4152	−	GGGGCGCGGUCGUGGGC	17	4637
  BCL11A-4153	−	AGGCCUUCCACCAGGUC	17	4638
  BCL11A-4154	+	UCCCGUGCCGCUGCGCC	17	4639
  BCL11A-4155	−	CAGAACACUCAUGGAUU	17	4640
  BCL11A-4156	+	GCUCCCCGGGCGGUGUG	17	4641
  BCL11A-4157	−	GCCCGGGGAGCUGGACG	17	4642
  BCL11A-4158	+	UUGCAGUAACCUUUGCA	17	4643
  BCL11A-4159	−	AGACUUAGAGAGCUGGC	17	4644
  BCL11A-4160	−	GGCGCAGCCACACGGGC	17	4645
  BCL11A-4161	+	UUCUGCACCUAGUCCUG	17	4646
  BCL11A-4162	+	UUCUGUGCGUGUUGCAA	17	4647
  BCL11A-4163	−	CCCUGGCCACCCAUCAC	17	4648
  BCL11A-4164	+	AUAGGGCUGGGCCGGCC	17	4649
  BCL11A-4165	−	ACCAGGAUCAGUAUCGA	17	4650
  BCL11A-4166	+	UGAAGGGAUACCAACCC	17	4651
  BCL11A-4167	+	CUAGAGAAAUCCAUGGC	17	4652
  BCL11A-4168	+	CGGUGGAGAGACCGUCG	17	4653
  BCL11A-4169	−	UUUCUCUAGGAGACUUA	17	4654
  BCL11A-4170	+	GCAUGACUUGGACUUGA	17	4655
  BCL11A-4171	−	CUCGGGGCGCAGCGGCA	17	4656
  BCL11A-4172	+	GGUGGACUAAACAGGGG	17	4657
  BCL11A-4173	+	CCUCGCUGAAGUGCUGC	17	4658
  BCL11A-4174	+	CCAGGUUGCUCUGAAAU	17	4659
  BCL11A-4175	−	GCAUAGAGCGCCUGGGG	17	4660
  BCL11A-4176	−	GCAAGCUGAAGCGCCAC	17	4661
  BCL11A-4177	+	CUCGCUGAAGUGCUGCA	17	4662
  BCL11A-4178	−	GCACCCAGGCCAGCAAG	17	4663
  BCL11A-4179	+	GGGAGGCUCCAUAGCCA	17	4664
  BCL11A-4180	+	AGGCAAAAGGCGAUUGU	17	4665
  BCL11A-4181	−	GAUCCCUUCCUUAGCUU	17	4666
  BCL11A-4182	+	GUCUCCGAAGCUAAGGA	17	4667
  BCL11A-4183	+	CUUAGAGAAGGGGCUCA	17	4668
  BCL11A-4184	+	CUUUUUGGACAGGCCCC	17	4669
  BCL11A-4185	+	CUCGGGUGAUGGGUGGC	17	4670
  BCL11A-4186	+	GCCCACGACCGCGCCCC	17	4671
  BCL11A-4187	+	UUGUACAUGUGUAGCUG	17	4672
  BCL11A-4188	−	CCGUGGUGGCCAAGUUC	17	4673
  BCL11A-4189	−	GGAGAACGGGGACGAGG	17	4674
  BCL11A-4190	−	GCAGGCCCAGCUCAAAA	17	4675
  BCL11A-4191	+	UAUUCUUAGCAGGUUAA	17	4676
  BCL11A-4192	+	UCUGCAAUAUGAAUCCC	17	4677
  BCL11A-4193	+	UCCUAGAGAAAUCCAUG	17	4678
  BCL11A-4194	+	ACUUGACCGGGGGCUGG	17	4679
  BCL11A-4195	+	AGUCUCCGAAGCUAAGG	17	4680
  BCL11A-4196	+	GCUGGGCCUGCCCGGGC	17	4681
  BCL11A-4197	−	AGAUCCCUUCCUUAGCU	17	4682
  BCL11A-4198	+	CACACAUCUUGAGCUCU	17	4683
  BCL11A-4199	−	CCCGGGGAGCUGGACGG	17	4684
  BCL11A-4200	+	GAAGGGGCUCAGCGAGC	17	4685
  BCL11A-4201	−	GACUUAGAGAGCUGGCA	17	4686
  BCL11A-4202	+	UCCCAUGGAGAGGUGGC	17	4687
  BCL11A-4203	+	UGAAGUGCUGCAUGGAG	17	4688
  BCL11A-4204	+	ACAUUCUGCACCUAGUC	17	4689
  BCL11A-4205	+	CCCAUGGAGAGGUGGCU	17	4690
  BCL11A-4206	+	GCUCUCUGGGUACUACG	17	4691
  BCL11A-4207	−	CCACAGGGACACUUGCG	17	4692
  BCL11A-4208	−	GAGACUUAGAGAGCUGG	17	4693
  BCL11A-4209	−	UUGACAGGGUGCUGCGG	17	4694
  BCL11A-4210	−	CCGAGGCCGAGGGCCAC	17	4695
  BCL11A-4211	+	AGGGAUCUUUGAGCUGC	17	4696
  BCL11A-4212	+	AAGUAGAUUCUUAAUCC	17	4697
  BCL11A-4213	−	GCGCAGCGGCACGGGAA	17	4698
  BCL11A-4214	−	GCCGAGGCCGAGGGCCA	17	4699
  BCL11A-4215	−	AAGAUGUGUGGCAGUUU	17	4700
  BCL11A-4216	+	AGCUAAGGAAGGGAUCU	17	4701
  BCL11A-4217	+	CAGCUCUCUAAGUCUCC	17	4702
  BCL11A-4218	+	CCUAGAGAAAUCCAUGG	17	4703
  BCL11A-4219	−	ACCACGAGAACAGCUCG	17	4704
  BCL11A-4220	+	GCAAUAUGAAUCCCAUG	17	4705
  BCL11A-4221	−	CUCCAUGCAGCACUUCA	17	4706
  BCL11A-4222	−	UGUCCAAAAAGCUGCUG	17	4707
  BCL11A-4223	−	GAAUACCAGGAUCAGUA	17	4708
  BCL11A-4224	−	UCUCGGGGCGCAGCGGC	17	4709
  BCL11A-4225	−	AGUUUUCGGAUGGAAGC	17	4710
  BCL11A-4226	−	UCGUGGGCGUGGGCGAC	17	4711
  BCL11A-4227	+	UCGCGGCCGGGGGCAGG	17	4712
  BCL11A-4228	−	CUACUUAGAAAGCGAAC	17	4713
  BCL11A-4229	+	GGGUUAUUGUCUGCAAU	17	4714
  BCL11A-4230	+	CUUGACCGGGGGCUGGG	17	4715
  BCL11A-4231	−	UGGAUUAAGAAUCUACU	17	4716
  BCL11A-4232	−	GGCUUCCGGCCUGGCAG	17	4717
  BCL11A-4233	−	CUUCCACCAGGUCCUGG	17	4718
  BCL11A-4234	+	CGCUUCAGCUUGCUGGC	17	4719
  BCL11A-4235	−	CAUAGAGCGCCUGGGGG	17	4720
  BCL11A-4236	+	CCUGGUGGAAGGCCUCG	17	4721
  BCL11A-4237	−	UCCACCAGGUCCUGGGC	17	4722
  BCL11A-4238	+	CUGCAAUAUGAAUCCCA	17	4723
  BCL11A-4239	−	GCUGGACGGAGGGAUCU	17	4724
  BCL11A-4240	+	UUGACCGGGGGCUGGGA	17	4725
  BCL11A-4241	−	UUCCCAGCCACCUCUCC	17	4726
  BCL11A-4242	+	UUUUGAGCUGGGCCUGC	17	4727
  BCL11A-4243	−	GCUUCUCCACACCGCCC	17	4728
  BCL11A-4244	+	AGAGAAACCAUGCACUG	17	4729
  BCL11A-4245	−	AGCUGGACGGAGGGAUC	17	4730
  BCL11A-4246	+	CCGGGGAGCUGGCGGUG	17	4731
  BCL11A-4247	+	AUCCCAUGGAGAGGUGG	17	4732
  BCL11A-4248	+	GUUCCGGGGAGCUGGCG	17	4733
  BCL11A-4249	+	GACUAAACAGGGGGGGA	17	4734
  BCL11A-4250	+	UGCCCAGCAGCAGCUUU	17	4735
  BCL11A-4251	+	GGGAUCUUUGAGCUGCC	17	4736
  BCL11A-4252	−	UCCCAGCCACCUCUCCA	17	4737
  BCL11A-4253	−	CAGCGGCACGGGAAGUG	17	4738
  BCL11A-4254	+	UUCCGGGGAGCUGGCGG	17	4739
  BCL11A-4255	+	UCCUCGUCCCCGUUCUC	17	4740
  BCL11A-4256	−	GCGGCACGGGAAGUGGA	17	4741
  BCL11A-4257	−	UGGGCAGCCCCAGCUCG	17	4742
  BCL11A-4258	−	CGCAGCGGCACGGGAAG	17	4743
  BCL11A-4259	−	CCGCCCGGGGAGCUGGA	17	4744
  BCL11A-4260	+	AUGGAGAGGUGGCUGGG	17	4745
  BCL11A-4261	+	CUCCUCGUCCCCGUUCU	17	4746
  BCL11A-4262	−	UACUUAGAAAGCGAACA	17	4747
  BCL11A-4263	−	GGGCAGGCCCAGCUCAA	17	4748
  BCL11A-4264	−	ACCGCCCGGGGAGCUGG	17	4749
  BCL11A-4265	+	AAACAGGGGGGGAGUGG	17	4750
  BCL11A-4266	+	CGGGGGCUGGGAGGGAG	17	4751
  BCL11A-4267	+	CCGGCCUGGGGACAGCG	17	4752
  BCL11A-4268	+	UAGGGCUGGGCCGGCCU	17	4753
  BCL11A-4269	−	AAGAAUCUACUUAGAAA	17	4754
  BCL11A-4270	+	AACAGGGGGGGAGUGGG	17	4755
  BCL11A-4271	+	ACCGGGGGCUGGGAGGG	17	4756
  BCL11A-4272	−	GGUCGUGGGCGUGGGCG	17	4757
  BCL11A-4273	+	GGAGGGGGGGCGUCGCC	17	4758
  BCL11A-4274	−	GAACGGGGACGAGGAGG	17	4759
  BCL11A-4275	+	GACCGGGGGCUGGGAGG	17	4760
  BCL11A-4276	+	GGGAGGGGGGGCGUCGC	17	4761
  BCL11A-4277	+	GGGGGCUGGGAGGGAGG	17	4762
  BCL11A-4278	−	AGCGGCACGGGAAGUGG	17	4763
  BCL11A-4279	+	GAUUGCAGAGGAGGGAG	17	4764
  BCL11A-4280	+	GGGGGGGCGUCGCCAGG	17	4765
  BCL11A-4281	+	GGAUUGCAGAGGAGGGA	17	4766
  BCL11A-4282	+	GGGCGGAUUGCAGAGGA	17	4767
  BCL11A-4283	+	GCGGAUUGCAGAGGAGG	17	4768
  BCL11A-4284	−	GAGCUGACGGAGAGCGA	17	4769
  BCL11A-4285	+	GAAAACUGCCACACAUC	17	4770
  BCL11A-4286	+	AUUGCAGAGGAGGGAGG	17	4771
  BCL11A-4287	+	GGGGCGGAUUGCAGAGG	17	4772
  BCL11A-4288	+	CGGAUUGCAGAGGAGGG	17	4773
  BCL11A-4289	+	AGGGGCGGAUUGCAGAG	17	4774
  BCL11A-4290	−	ACGGGGACGAGGAGGAA	17	4775
  BCL11A-4291	+	GGAGGAGGGGCGGAUUG	17	4776
  BCL11A-4292	−	CGCUUCUCCACACCGCC	17	4777
  BCL11A-4293	−	UGACGGAGAGCGAGAGG	17	4778
  BCL11A-4294	−	AGGAGCUGACGGAGAGC	17	4779
  BCL11A-4295	+	GCUGGGAGGGAGGAGGG	17	4780
  BCL11A-4296	+	AGGAGGGGCGGAUUGCA	17	4781
  BCL11A-4297	+	UGUUGGGCAUCGCGGCC	17	4782
  BCL11A-4298	−	CGGGGACGAGGAGGAAG	17	4783
  BCL11A-4299	+	GGAGGGGCGGAUUGCAG	17	4784
  BCL11A-4300	−	GGAGGAGCUGACGGAGA	17	4785
  BCL11A-4301	−	GGGACGAGGAGGAAGAG	17	4786
  BCL11A-4302	−	AGGAGGAGGAGCUGACG	17	4787
  BCL11A-4303	−	ACGAGGAAGAGGAAGAA	17	4788
  BCL11A-4304	−	AGGAAGAGGAAGAAGAG	17	4789
  BCL11A-4305	−	AGGAAGAGGAGGACGAC	17	4790
  BCL11A-4306	−	AGGAGGACGACGAGGAA	17	4791
  BCL11A-4307	−	GGAGGAGGAGGAGCUGA	17	4792
  BCL11A-4308	−	GGAAGAGGAGGACGACG	17	4793
  BCL11A-4309	−	GGAGGAAGAGGAGGACG	17	4794
  BCL11A-4310	−	GGAAGAGGAAGAAGAGG	17	4795
  BCL11A-4311	−	AGGAGGAGGAGGAGCUG	17	4796
  BCL11A-4312	−	CGAGGAAGAGGAAGAAG	17	4797
  BCL11A-4313	−	GGACGACGAGGAAGAGG	17	4798
  BCL11A-4314	−	GGAGGACGACGAGGAAG	17	4799
  BCL11A-4315	−	CGACGAGGAAGAGGAAG	17	4800
  BCL11A-4316	−	AGAGGAGGACGACGAGG	17	4801
  BCL11A-4317	−	AAGAAGAGGAGGAAGAG	17	4802
  BCL11A-4318	−	AGGAAGAAGAGGAGGAA	17	4803
  BCL11A-4319	−	AGAGGAAGAAGAGGAGG	17	4804
  BCL11A-4320	−	AAGAGGAGGAAGAGGAG	17	4805
  BCL11A-4321	−	AGGAGGAAGAGGAGGAG	17	4806
  BCL11A-4322	−	GGAAGAAGAGGAGGAAG	17	4807
  BCL11A-4323	−	AGAAGAGGAGGAAGAGG	17	4808
  BCL11A-4324	−	AGAGGAGGAAGAGGAGG	17	4809
  BCL11A-4325	−	GGAGGAAGAGGAGGAGG	17	4810

• Table 6A 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 bind within first 500 bp 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 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 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 0-50 bp.
• 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 6A
  			Target	SEQ
  1st Tier	DNA		Site	ID
  gRNA Name	Strand	Targeting Domain	Length	NO
  BCL11A-4326	+	UUCUGCACUCAUCCCAGGCG	20	4811
  BCL11A-4327	−	AUCCAGGUCACGCCAGAGGA	20	4812
  BCL11A-4328	+	UGACCUGGAUGCCAACCUCC	20	4813
  BCL11A-4329	+	GGGAUUGGAUGCUUUUUUCA	20	4814
  BCL11A-4330	+	UGCACUCAUCCCAGGCG	17	4815
  BCL11A-4331	−	CAGGUCACGCCAGAGGA	17	4816
  BCL11A-4332	+	CCUGGAUGCCAACCUCC	17	4817
  BCL11A-4333	+	AUUGGAUGCUUUUUUCA	17	4818

• Table 6B provides exemplary targeting domains for knocking out the BCL11A gene by targeting the early coding sequence the BCL11A gene. The targeting domains target outside the first 500 bp 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.
• 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 0-50 bp.
• 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 6B
  			Target	SEQ
  	DNA		Site	ID
  gRNA Name	Strand	Targeting Domain	Length	NO
  BCL11A-4334	−	GCUAUGGAGCCUCCCGC	17	4819
  BCL11A-4335	+	GACUUGACCGUCAUGGG	17	4820
  BCL11A-4336	+	UCCGACGAGGAGGCAAA	17	4821
  BCL11A-4337	+	CGGGAGGCUCCAUAGCC	17	4822
  BCL11A-4338	+	UCCGUGUUCGCUUUCUA	17	4823
  BCL11A-4339	−	AACACGCACAGAACACU	17	4824
  BCL11A-4340	−	UUCCCAGCCACCUCUCC	17	4825
  BCL11A-4341	+	GGCUGGGAGGGAGGAGG	17	4826
  BCL11A-4342	+	UCGGACUUGACCGUCAUGGG	20	4827
  BCL11A-4343	−	AUGGCUAUGGAGCCUCCCGC	20	4828
  BCL11A-4344	+	UGCUCCGACGAGGAGGCAAA	20	4829
  BCL11A-4345	+	UGGCGGGAGGCUCCAUAGCC	20	4830
  BCL11A-4346	−	UGCAACACGCACAGAACACU	20	4831
  BCL11A-4347	+	ACUUCCGUGUUCGCUUUCUA	20	4832
  BCL11A-4348	−	UCCUUCCCAGCCACCUCUCC	20	4833
  BCL11A-4349	+	GGGGGCUGGGAGGGAGGAGG	20	4834

• Table 7A 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 bind within a region 5′ (51.5 to 51.7 kb downstream of transcription start site, TSS) or 3′ (65.1 to 65.3 kb 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.
• 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 0-50 bp. Exemplary gRNA pairs are: BCL11A-5210 and BCL11A-5204, BCL11A-5211 and BCL11A-5204, BCL11A-5172 and BCL11A-5176, BCL11A-5172 and BCL11A-5186, BCL11A-5179 and BCL11A-5176, or BCL11A-5179 and BCL11A-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 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. For example, gRNA pairs that target upstream (i.e., 5′) of the enhancer region in the BCL11A gene (e.g., BCL11A-5210 and BCL11A-5204, or BCL11A-5211 and BCL11A-5204) can be paired with gRNA pairs that target downstream (i.e., 3′) of the enhancer region in the BCL11A gene (e.g., BCL11A-5172 and BCL11A-5176, BCL11A-5172 and BCL11A-5186, BCL11A-5179 and BCL11A-5176, or BCL11A-5179 and BCL11A-5186).

• TABLE 7A
  			Target
  	5′ or	SEQ
  1st Tier	DNA	Targeting	Site		3′ of	ID
  gRNA Name	Strand	Domain	Length	repeats	NO
  BCL11A-5172	+	GAAAAUACUU		20	3′	4835
  		ACUGUACUGC
  BCL11A-5173	−	GAAAGCAGUG	17	5′	4836
  		UAAGGCU
  BCL11A-5174	−	GGCUGUUUUG	20	5′	4837
  		GAAUGUAGAG
  BCL11A-5175	+	GUGCUACUUA		20	3′	4838
  		UACAAUUCAC

• Table 7B provides exemplary targeting domains for removing (e.g., deleting) the enhancer region in the BCL11A gene selected according to second tier parameters. The targeting domains bind within a region 5′ (51.5 to 51.7 kb downstream of transcription start site, TSS) or 3′ (65.1 to 65.3 kb 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 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. 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 0-50 bp. 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 bind within a region 5′ (51.5 to 51.7 kb downstream of transcription start site, TSS) or 3′ (65.1 to 65.3 kb 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.
• 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 0-50 bp.
• 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 7B
  			Target
  2nd Tier	DNA		Site		5′ or 3′ of	SEQ ID
  gRNA Name	Strand	Targeting Domain	Length	repeats	NO

  BCL11A-5176	−	AAACUAUUUACAGCCAUAAC	20	3′	4839
  BCL11A-5177	+	AAAUACUUACUGUACUGCAG		20	3′	4840
  BCL11A-5178	−	AACUAUUUACAGCCAUAACA	20	3′	4841
  BCL11A-5179	+	AAUACUUACUGUACUGC		17	3′	4842
  BCL11A-5180	+	ACAACUUGUGUUGCACU		17	5′	4843
  BCL11A-5181	+	AUACUUACUGUACUGCA		17	3′	4844
  BCL11A-5182	+	AUUCACUGGAAACCCUGUUA		20	3′	4845
  BCL11A-5183	+	AUUUAAGACGGGAAAAC		17	5′	4846
  BCL11A-5184	+	CACUGGAAACCCUGUUA		17	3′	4847
  BCL11A-5185	+	CUACUUAUACAAUUCAC		17	3′	4848
  BCL11A-5186	−	CUAUUUACAGCCAUAAC	17	3′	4849
  BCL11A-5187	−	UAAGAAAGCAGUGUAAGGCU	20	5′	4850
  BCL11A-5188	+	UACACAACUUGUGUUGCACU		20	5′	4851
  BCL11A-5189	+	UACUGUACUGCAGGGGAAUU		20	3′	4852
  BCL11A-5190	+	UACUUACUGUACUGCAG		17	3′	4853
  BCL11A-5191	+	UGUACUGCAGGGGAAUU		17	3′	4854

• 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 bind within a region 5′ (51.5 to 51.7 kb downstream of transcription start site, TSS) or 3′ (65.1 to 65.3 kb 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 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. 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 0-50 bp. 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 bind within a region 5′ (51.5 to 51.7 kb downstream of transcription start site, TSS) or 3′ (65.1 to 65.3 kb 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.
• 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 0-50 bp.
• 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 7C
  			Target
  3rd Tier	DNA		Site		5′ or 3′ of	SEQ ID
  gRNA Name	Strand	Targeting Domain	Length	repeats	NO
  BCL11A-5192	−	GAAUGUAGAGAGGCAGA	17	5′	4855
  BCL11A-5193	−	GGAAUGUAGAGAGGCAG	17	5′	4856
  BCL11A-5194	−	GUAAGUAUUUUCUUUCAUUG	20	3′	4857
  BCL11A-5195	−	GUAAUUAAGAAAGCAGUGUA	20	5′	4858
  BCL11A-5196	−	GUAUUUUCUUUCAUUGG	17	3′	4859

• Table 7D 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 bind within a region 5′ (51.5 to 51.7 kb downstream of transcription start site, TSS) or 3′ (65.1 to 65.3 kb 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 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. 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 0-50 bp. 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 bind within a region 5′ (51.5 to 51.7 kb downstream of transcription start site, TSS) or 3′ (65.1 to 65.3 kb 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.
• 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 0-50 bp.
• 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 7D
  			Target
  4th Tier	DNA		Site	5′ or 3′ of	SEQ ID
  gRNA Name	Strand	Targeting Domain	Length	repeats	NO
  BCL11A-5197	−	AAAAUAAUUAGAAUAAA	17	5′	4860
  BCL11A-5198	+	AAAAUACUUACUGUACUGCA	20	3′	4861
  BCL11A-5199	+	AAAAUUUAAGACGGGAAAAC	20	5′	4862
  BCL11A-5200	−	AAGUAUUUUCUUUCAUU	17	3′	4863
  BCL11A-5201	−	AAUGUAGAGAGGCAGAG	17	5′	4864
  BCL11A-5202	+	ACAUAAAAAUUUAAGAC	17	5′	4865
  BCL11A-5203	−	AGAAAGCAGUGUAAGGC	17	5′	4866
  BCL11A-5204	−	AGAAUAAAAGGCUGUUU	17	5′	4867
  BCL11A-5205	−	AGUAAAAUAAUUAGAAUAAA	20	5′	4868
  BCL11A-5206	−	AGUAAGUAUUUUCUUUCAUU	20	3′	4869
  BCL11A-5207	−	AGUAUUUUCUUUCAUUG	17	3′	4870
  BCL11A-5208	−	AUUAAGAAAGCAGUGUA	17	5′	4871
  BCL11A-5209	−	AUUAGAAUAAAAGGCUGUUU	20	5′	4872
  BCL11A-5210	+	AUUAUUUUACUAGUGAAUUA	20	5′	4873
  BCL11A-5211	+	AUUUUACUAGUGAAUUA	17	5′	4874
  BCL11A-5212	+	CACAUAAAAAUUUAAGA	17	5′	4875
  BCL11A-5213	−	CAGUAAGUAUUUUCUUUCAU	20	3′	4876
  BCL11A-5214	+	CUCACAUAAAAAUUUAAGAC	20	5′	4877
  BCL11A-5215	−	UAAGUAUUUUCUUUCAU	17	3′	4878
  BCL11A-5216	−	UAAGUAUUUUCUUUCAUUGG	20	3′	4879
  BCL11A-5217	−	UAUUUACAGCCAUAACA	17	3′	4880
  BCL11A-5218	+	UCUCACAUAAAAAUUUAAGA	20	5′	4881
  BCL11A-5219	−	UGGAAUGUAGAGAGGCAGAG	20	5′	4882
  BCL11A-5220	−	UGUUUUGGAAUGUAGAG	17	5′	4883
  BCL11A-5221	−	UUAAGAAAGCAGUGUAAGGC	20	5′	4884
  BCL11A-5222	−	UUGGAAUGUAGAGAGGCAGA	20	5′	4885
  BCL11A-5223	−	UUUGGAAUGUAGAGAGGCAG	20	5′	4886

• Table 8A 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 bind within a region 5′ (51.5 to 51.7 kb downstream of transcription start site, TS S) or 3′ (65.1 to 65.3 kb 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.
• 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 0-50 bp.
• 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 8A
  			Target
  1st Tier	DNA		Site		5′ or 3′ of	SEQ ID
  gRNA Name	Strand	Targeting Domain	Length	repeats	NO
  BCL11A-5224	−	GAGGGGCUGAUAUAACUUCU	20	5′	4887
  BCL11A-5225	+	GCUACUUAUACAAUUCA		17	3′	4888
  BCL11A-5226	−	GGGCUGAUAUAACUUCU	17	5′	4889
  BCL11A-5227	−	GUCUUAAAUUUUUAUGUGAG	20	5′	4890
  BCL11A-5228	+	GUGCUACUUAUACAAUUCAC		20	3′	4891

• Table 8B provides exemplary targeting domains for removing (e.g., deleting) the enhancer region in the BCL11A gene selected according to second tier parameters. The targeting domains bind within a region 5′ (51.5 to 51.7 kb downstream of transcription start site, TSS) or 3′ (65.1 to 65.3 kb 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 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 0-50 bp. 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 bind within a region 5′ (51.5 to 51.7 kb downstream of transcription start site, TSS) or 3′ (65.1 to 65.3 kb 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.
• 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 0-50 bp.
• 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 8B
  			Target
  2nd Tier	DNA		Site		5′ or 3′ of	SEQ ID
  gRNA Name	Strand	Targeting Domain	Length	repeats	NO

  BCL11A-5229	−	AACACAAGUUGUGUAGA	17	5′	4892
  BCL11A-5230	−	ACUAUUUACAGCCAUAA	17	3′	4893
  BCL11A-5231	−	AGCACACUGCUGUAAUU	17	5′	4894
  BCL11A-5232	+	AGUGCUACUUAUACAAUUCA		20	3′	4895
  BCL11A-5233	+	AUAGUUUGCUUCCCCCA		17	3′	4896
  BCL11A-5234	−	AUGAGCACACUGCUGUAAUU	20	5′	4897
  BCL11A-5235	−	CAAACUAUUUACAGCCAUAA	20	3′	4898
  BCL11A-5236	−	CAGCCAUAACAGGGUUUCCA	20	3′	4899
  BCL11A-5237	−	CCAUAACAGGGUUUCCA	17	3′	4900
  BCL11A-5238	+	CUACUUAUACAAUUCAC		17	3′	4901
  BCL11A-5239	−	CUUUGGCUAUUGAUACUGAU	20	3′	4902
  BCL11A-5240	+	UAAAUAGUUUGCUUCCCCCA		20	3′	4903
  BCL11A-5241	+	UAGUUUGCUUCCCCCAAUGA		20	3′	4904
  BCL11A-5242	−	UGCAACACAAGUUGUGUAGA	20	5′	4905
  BCL11A-5243	−	UGGAAUGUAGAGAGGCA	17	5′	4906
  BCL11A-5244	−	UGGCUAUUGAUACUGAU	17	3′	4907
  BCL11A-5245	+	UUUGCUUCCCCCAAUGA		17	3′	4908
  BCL11A-5246	−	UUUUGGAAUGUAGAGAGGCA	20	5′	4909

• Table 8C 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 bind within a region 5′ (51.5 to 51.7 kb downstream of transcription start site, TS S) or 3′ (65.1 to 65.3 kb 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 0-50 bp. 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 bind within a region 5′ (51.5 to 51.7 kb downstream of transcription start site, TSS) or 3′ (65.1 to 65.3 kb 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.
• 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 0-50 bp.
• 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 8C
  			Target
  3rd Tier	DNA		Site		5′ or 3′ of	SEQ ID
  gRNA Name	Strand	Targeting Domain	Length	repeats	NO

  BCL11A-5247	+	GAAAAUACUUACUGUACUGC		20	3′	4910
  BCL11A-5248	−	GAAUUGUAUAAGUAGCA	17	3′	4911
  BCL11A-5249	−	GAGUUCUGUGUCAGCAAAAA	20	3′	4912
  BCL11A-5250	+	GGAAAACAGGAAGAUGCAUU		20	5′	4913
  BCL11A-5251	−	GGAAUGUAGAGAGGCAG	17	5′	4914
  BCL11A-5252	−	GGCUGUUUUGGAAUGUA	17	5′	4915
  BCL11A-5253	−	GUAAGUAUUUUCUUUCA	17	3′	4916
  BCL11A-5254	−	GUAAGUAUUUUCUUUCAUUG	20	3′	4917
  BCL11A-5255	−	GUAUUUUCUUUCAUUGG	17	3′	4918

• Table 8D 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 bind within a region 5′ (51.5 to 51.7 kb downstream of transcription start site, TSS) or 3′ (65.1 to 65.3 kb 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 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 0-50 bp. 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 bind within a region 5′ (51.5 to 51.7 kb downstream of transcription start site, TSS) or 3′ (65.1 to 65.3 kb 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.
• 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 0-50 bp.
• 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 8D
  			Target
  4th Tier	DNA		Site	5′ or 3′ of	SEQ ID
  gRNA Name	Strand	Targeting Domain	Length	repeats	NO
  BCL11A-5256	+	AAAAAUUUAAGACGGGAAAA	20	5′	4919
  BCL11A-5257	+	AAAACAGGAAGAUGCAUUCU	20	5′	4920
  BCL11A-5258	−	AAAACUAGAAAGUUUUA	17	3′	4921
  BCL11A-5259	+	AAAAUACUUACUGUACUGCA	20	3′	4922
  BCL11A-5260	+	AAAAUUUAAGACGGGAAAAC	20	5′	4923
  BCL11A-5261	+	AAACAGGAAGAUGCAUU	17	5′	4924
  BCL11A-5262	−	AAAGGCUGUUUUGGAAUGUA	20	5′	4925
  BCL11A-5263	+	AAAUACUUACUGUACUG	17	3′	4926
  BCL11A-5264	+	AAAUACUUACUGUACUGCAG	20	3′	4927
  BCL11A-5265	−	AAGAAAGCAGUGUAAGG	17	5′	4928
  BCL11A-5266	−	AAGGCUGUUUUGGAAUG	17	5′	4929
  BCL11A-5267	−	AAGUAUUUUCUUUCAUU	17	3′	4930
  BCL11A-5268	+	AAUACUUACUGUACUGC	17	3′	4931
  BCL11A-5269	−	AAUUAGAAUAAAAGGCUGUU	20	5′	4932
  BCL11A-5270	+	AAUUAUUUUACUAGUGAAUU	20	5′	4933
  BCL11A-5271	+	AAUUUAAGACGGGAAAA	17	5′	4934
  BCL11A-5272	+	ACAGGAAGAUGCAUUCU	17	5′	4935
  BCL11A-5273	−	ACAGUAAGUAUUUUCUUUCA	20	3′	4936
  BCL11A-5274	+	ACAUAAAAAUUUAAGAC	17	5′	4937
  BCL11A-5275	+	ACUUUCUAGUUUUGCUUAAC	20	3′	4938
  BCL11A-5276	+	AGAAAAUACUUACUGUACUG	20	3′	4939
  BCL11A-5277	−	AGAAUAAAAGGCUGUUU	17	5′	4940
  BCL11A-5278	−	AGCAAAACUAGAAAGUUUUA	20	3′	4941
  BCL11A-5279	−	AGUAAGUAUUUUCUUUCAUU	20	3′	4942
  BCL11A-5280	−	AGUAUUUUCUUUCAUUG	17	3′	4943
  BCL11A-5281	−	AGUGAAUUGUAUAAGUAGCA	20	3′	4944
  BCL11A-5282	+	AUACUUACUGUACUGCA	17	3′	4945
  BCL11A-5283	+	AUCUCACAUAAAAAUUUAAG	20	5′	4946
  BCL11A-5284	−	AUUAAGAAAGCAGUGUAAGG	20	5′	4947
  BCL11A-5285	−	AUUAGAAUAAAAGGCUGUUU	20	5′	4948
  BCL11A-5286	+	AUUAUUUUACUAGUGAAUUA	20	5′	4949
  BCL11A-5287	+	AUUUAAGACGGGAAAAC	17	5′	4950
  BCL11A-5288	+	AUUUUACUAGUGAAUUA	17	5′	4951
  BCL11A-5289	−	AUUUUCAUGUUAAGCAAAAC	20	3′	4952
  BCL11A-5290	+	CACAUAAAAAUUUAAGA	17	5′	4953
  BCL11A-5291	−	CAGUAAGUAUUUUCUUUCAU	20	3′	4954
  BCL11A-5292	−	CCGUCUUAAAUUUUUAU	17	5′	4955
  BCL11A-5293	+	CUCACAUAAAAAUUUAAGAC	20	5′	4956
  BCL11A-5294	−	UAAAAGGCUGUUUUGGAAUG	20	5′	4957
  BCL11A-5295	−	UAAGUAUUUUCUUUCAU	17	3′	4958
  BCL11A-5296	−	UAAGUAUUUUCUUUCAUUGG	20	3′	4959
  BCL11A-5297	−	UAAUUCACUAGUAAAAUAAU	20	5′	4960
  BCL11A-5298	+	UACUUACUGUACUGCAG	17	3′	4961
  BCL11A-5299	−	UAGAAUAAAAGGCUGUU	17	5′	4962
  BCL11A-5300	+	UAUUUUACUAGUGAAUU	17	5′	4963
  BCL11A-5301	+	UCACAUAAAAAUUUAAG	17	5′	4964
  BCL11A-5302	+	UCUCACAUAAAAAUUUAAGA	20	5′	4965
  BCL11A-5303	+	UGUUUCAUUUUUUGCUGACA	20	3′	4966
  BCL11A-5304	−	UGUUUUGGAAUGUAGAGAGG	20	5′	4967
  BCL11A-5305	−	UUAAAUUUUUAUGUGAG	17	5′	4968
  BCL11A-5306	+	UUAUUCUAAUUAUUUUACUA	20	5′	4969
  BCL11A-5307	−	UUCACUAGUAAAAUAAU	17	5′	4970
  BCL11A-5308	−	UUCAUGUUAAGCAAAAC	17	3′	4971
  BCL11A-5309	+	UUCAUUUUUUGCUGACA	17	3′	4972
  BCL11A-5310	−	UUCCCGUCUUAAAUUUUUAU	20	5′	4973
  BCL11A-5311	+	UUCUAAUUAUUUUACUA	17	5′	4974
  BCL11A-5312	+	UUCUAGUUUUGCUUAAC	17	3′	4975
  BCL11A-5313	−	UUCUGUGUCAGCAAAAA	17	3′	4976
  BCL11A-5314	−	UUUGGAAUGUAGAGAGG	17	5′	4977
  BCL11A-5315	−	UUUGGAAUGUAGAGAGGCAG	20	5′	4978

• Table 9 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 bind within a region 5′ (51.5 to 51.7 kb downstream of transcription start site, TSS) or 3′ (65.1 to 65.3 kb 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 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 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 0-50 bp.
• 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 9
  			Target
  1st Tier	DNA		Site		5′ or 3′ of	SEQ ID
  gRNA Name	Strand	Targeting Domain	Length	repeats	NO
  BCL11A-5316	−	UUUGGAUCUUUGGCUAUUGA	20	3′	4979
  BCL11A-5317	−	GGAUCUUUGGCUAUUGA	17	3′	4980

• Table 10A provides exemplary targeting domains for knocking down expression of the BCL11A gene according to first tier parameters. The targeting domains bind between 500 bp upstream and 500 bp 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 500 bp upstream and 500 bp 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 10A
  1st Tier	DNA		Target Site	SEQ ID
  gRNA Name	Strand	Targeting Domain	Length	NO
  BCL11A-4350	+	GACGACGGCUCGGUUCACAU		20	4981
  BCL11A-4351	+	GACGCCAGACGCGGCCCCCG		20	4982
  BCL11A-4352	+	GCCUUGCUUGCGGCGAGACA		20	4983
  BCL11A-4353	+	GGCUCCGCGGACGCCAGACG		20	4984
  BCL11A-4354	+	GACGGCUCGGUUCACAU		17	4985
  BCL11A-4355	−	GCCGCGUCUGGCGUCCG	17	4986
  BCL11A-4356	+	GCGGGCGGACGACGGCU		17	4987

• Table 10B provides exemplary targeting domains for knocking down expression of the BCL11A gene according to second tier parameters. The targeting domains bind between 500 bp upstream and 500 bp 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 500 bp upstream and 500 bp 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 10B
  2nd Tier	DNA		Target Site	SEQ ID
  gRNA Name	Strand	Targeting Domain	Length	NO
  BCL11A-4357	+	ACACGGCAAUGGUUCCAGAU		20	4988
  BCL11A-4358	−	ACCAUGUCUCGCCGCAAGCA	20	4989
  BCL11A-4359	+	ACGACGGCUCGGUUCACAUC		20	4990
  BCL11A-4360	+	AUUCCCGUUUGCUUAAGUGC		20	4991
  BCL11A-4361	−	CAUUUUAGAGUCCGCGUGUG	20	4992
  BCL11A-4362	+	CGGACGCCAGACGCGGCCCC		20	4993
  BCL11A-4363	+	CGGUUCACAUCGGGAGAGCC		20	4994
  BCL11A-4364	−	CUCCUGACGUUCAAGUUCGC	20	4995
  BCL11A-4365	−	UAAUAAUCACGAGAGCGCGC	20	4996
  BCL11A-4366	−	UCCUGACGUUCAAGUUCGCA	20	4997
  BCL11A-4367	+	UCGGUUCACAUCGGGAGAGC		20	4998
  BCL11A-4368	+	UCUUUUACCUCGACUCUCGG		20	4999
  BCL11A-4369	+	UGCUUGCGGCGAGACAUGGU		20	5000
  BCL11A-4370	−	UUUAGAGUCCGCGUGUGUGG	20	5001
  BCL11A-4371	+	ACGGCUCGGUUCACAUC		17	5002
  BCL11A-4372	−	AUGUCUCGCCGCAAGCA	17	5003
  BCL11A-4373	−	CUGACGUUCAAGUUCGC	17	5004
  BCL11A-4374	−	UAAUCACGAGAGCGCGC	17	5005
  BCL11A-4375	+	UCCGCGGACGCCAGACG		17	5006
  BCL11A-4376	−	UGACGUUCAAGUUCGCA	17	5007
  BCL11A-4377	−	UUAGAGUCCGCGUGUGU	17	5008
  BCL11A-4378	+	UUGCGGCGAGACAUGGU		17	5009
  BCL11A-4379	+	UUGCUUGCGGCGAGACA		17	5010
  BCL11A-4380	+	UUUACCUCGACUCUCGG		17	5011
  BCL11A-4381	−	UUUAGAGUCCGCGUGUG	17	5012

• Table 10C provides exemplary targeting domains for knocking down expression of the BCL11A gene according to third tier parameters. The targeting domains bind between 500 bp upstream and 500 bp 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 500 bp upstream and 500 bp 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 10C
  3rd Tier	DNA		Target Site	SEQ ID
  gRNA Name	Strand	Targeting Domain	Length	NO
  BCL11A-4382	−	GAAAAAACCCUCAUCCCAUC	20	5013
  BCL11A-4383	+	GAAAGGGGUGGCAGGGG	17	5014
  BCL11A-4384	+	GAACUUGAACGUCAGGAGUC	20	5015
  BCL11A-4385	−	GAACUUGCAGCUCAGGG	17	5016
  BCL11A-4386	+	GAAGAAAGGGGUGGCAG	17	5017
  BCL11A-4387	+	GAAGAAAGGGGUGGCAGGGG	20	5018
  BCL11A-4388	+	GAAGGGGAAGCUCACACCAA	20	5019
  BCL11A-4389	+	GAAGGGGAGGAGGGAAG	17	5020
  BCL11A-4390	+	GAAUUGUGGGAGAGCCGUCA	20	5021
  BCL11A-4391	+	GACAAGCCAAUGGCCAGUGC	20	5022
  BCL11A-4392	+	GACAGAGACACACAAAACAU	20	5023
  BCL11A-4393	+	GACAUGAAAAAGAGACC	17	5024
  BCL11A-4394	+	GACAUGGUGGGCUGCGGGGC	20	5025
  BCL11A-4395	+	GACGCGGCCCCCGGGGG	17	5026
  BCL11A-4396	−	GACUAGAAGCAAAAGCG	17	5027
  BCL11A-4397	−	GACUAGAAGCAAAAGCGAGG	20	5028
  BCL11A-4398	+	GAGAAGAAAGGGGUGGC	17	5029
  BCL11A-4399	+	GAGAAGGGGAGGAGGGA	17	5030
  BCL11A-4400	+	GAGACACACAAAACAUGGGC	20	5031
  BCL11A-4401	+	GAGACAUGGUGGGCUGC	17	5032
  BCL11A-4402	+	GAGAGAAGAAAGGGGUGGCA	20	5033
  BCL11A-4403	+	GAGAGAAGAGAGAUAGA	17	5034
  BCL11A-4404	+	GAGAGAAGGGGAGGAGGGAA	20	5035
  BCL11A-4405	+	GAGAGAGAGAAGAGAGAUAG	20	5036
  BCL11A-4406	+	GAGAGAGAUGAAAAAAA	17	5037
  BCL11A-4407	+	GAGCAGGAGAGAAGGGG	17	5038
  BCL11A-4408	+	GAGCAGGAGAGAAGGGGAGG	20	5039
  BCL11A-4409	+	GAGCCGGGUUAGAAAGA	17	5040
  BCL11A-4410	+	GAGGGGAGGGGGCGCUG	17	5041
  BCL11A-4411	+	GAGGGGCGGGCCGAGGGGAG	20	5042
  BCL11A-4412	+	GAGGGGGAGGUGCGGGG	17	5043
  BCL11A-4413	+	GAGGGGGAGGUGCGGGGCGG	20	5044
  BCL11A-4414	−	GAGGUAAAAGAGAUAAA	17	5045
  BCL11A-4415	−	GAGUCCGCGUGUGUGGG	17	5046
  BCL11A-4416	−	GAGUCUCCUUCUUUCUAACC	20	5047
  BCL11A-4417	−	GAUGAAGAUAUUUUCUC	17	5048
  BCL11A-4418	−	GCAAAAGCGAGGGGGAGAGA	20	5049
  BCL11A-4419	−	GCACCUCCCCCUCCCCGCAC	20	5050
  BCL11A-4420	−	GCACUUGAACUUGCAGCUCA	20	5051
  BCL11A-4421	+	GCAGGGAAGAUGAAUUG	17	5052
  BCL11A-4422	+	GCAGGGCGAGCAGGAGAGAA	20	5053
  BCL11A-4423	+	GCAGGGGUGGGAGGAAA	17	5054
  BCL11A-4424	+	GCAGGGGUGGGAGGAAAGGG	20	5055
  BCL11A-4425	+	GCCAAUGGCCAGUGCGGGGA	20	5056
  BCL11A-4426	−	GCCACCCCUUUCUUCUCUCC	20	5057
  BCL11A-4427	+	GCCAGACGCGGCCCCCG	17	5058
  BCL11A-4428	−	GCCCCAGCGCCCCCUCCCCU	20	5059
  BCL11A-4429	+	GCCCCCGGGGGAGGGGC	17	5060
  BCL11A-4430	−	GCCCGCCCCUCCCCCGG	17	5061
  BCL11A-4431	+	GCCGAGGGGAGGGGGCGCUG	20	5062
  BCL11A-4432	+	GCCGCGGCGGUGGCGUGGCC	20	5063
  BCL11A-4433	+	GCCGGGAGAGAAGAAAG	17	5064
  BCL11A-4434	+	GCCGGGAGAGAAGAAAGGGG	20	5065
  BCL11A-4435	+	GCGAGACAUGGUGGGCUGCG	20	5066
  BCL11A-4436	+	GCGCAGGGAAGAUGAAUUGU	20	5067
  BCL11A-4437	+	GCGCCGCGGCGGUGGCG	17	5068
  BCL11A-4438	−	GCGCUCGCUGCGGCCAC	17	5069
  BCL11A-4439	+	GCGGCCCCCGGGGGAGGGGC	20	5070
  BCL11A-4440	−	GCGGCGCUCGCUGCGGCCAC	20	5071
  BCL11A-4441	+	GCGGCGGCGGCGGCGGC	17	5072
  BCL11A-4442	+	GCGGCGGCGGCGGCGGCGGC	20	5073
  BCL11A-4443	+	GCGGCGGCGGCGGCGGCGGG	20	5074
  BCL11A-4444	+	GCGGCGGCGGCGGCGGG	17	5075
  BCL11A-4445	+	GCGGCGGGCGGACGACGGCU	20	5076
  BCL11A-4446	+	GCGGCGGUGGCGUGGCC	17	5077
  BCL11A-4447	+	GCGGGCGGCGGCGGCGG	17	5078
  BCL11A-4448	+	GCGGGCGGCGGCGGCGGCGG	20	5079
  BCL11A-4449	+	GCGGGGAGGGGGAGGUG	17	5080
  BCL11A-4450	+	GCGUGGCCGGGAGAGAAGAA	20	5081
  BCL11A-4451	+	GCUCCCCCCCACACACG	17	5082
  BCL11A-4452	+	GCUGGGGUUUGCCUUGCUUG	20	5083
  BCL11A-4453	+	GGACAAGCCAAUGGCCAGUG	20	5084
  BCL11A-4454	+	GGACACACAUCAGGGGC	17	5085
  BCL11A-4455	+	GGACAGAGACACACAAAACA	20	5086
  BCL11A-4456	+	GGACGCCAGACGCGGCCCCC	20	5087
  BCL11A-4457	−	GGACUAGAAGCAAAAGCGAG	20	5088
  BCL11A-4458	+	GGAGAGAAGAAAGGGGUGGC	20	5089
  BCL11A-4459	+	GGAGAGAAGGGGAGGAGGGA	20	5090
  BCL11A-4460	+	GGAGAGCCGGGUUAGAAAGA	20	5091
  BCL11A-4461	+	GGAGGGGCGGGCCGAGGGGA	20	5092
  BCL11A-4462	+	GGAGGGGGAGGUGCGGGGCG	20	5093
  BCL11A-4463	+	GGAGGGGGCGCUGGGGCCGC	20	5094
  BCL11A-4464	+	GGCAGGGCGAGCAGGAGAGA	20	5095
  BCL11A-4465	+	GGCAGGGGUGGGAGGAA	17	5096
  BCL11A-4466	−	GGCCACUGGUGAGCCCG	17	5097
  BCL11A-4467	+	GGCCCCCGGGGGAGGGG	17	5098
  BCL11A-4468	−	GGCCCGCCCCUCCCCCG	17	5099
  BCL11A-4469	+	GGCCGAGGGGAGGGGGCGCU	20	5100
  BCL11A-4470	+	GGCCGCAGCGAGCGCCG	17	5101
  BCL11A-4471	+	GGCCGCAGCGAGCGCCGCGG	20	5102
  BCL11A-4472	+	GGCCGCGGGCUCACCAG	17	5103
  BCL11A-4473	+	GGCCGGGAGAGAAGAAA	17	5104
  BCL11A-4474	+	GGCGAGACAUGGUGGGCUGC	20	5105
  BCL11A-4475	+	GGCGAGCAGGAGAGAAG	17	5106
  BCL11A-4476	+	GGCGAGCAGGAGAGAAGGGG	20	5107
  BCL11A-4477	+	GGCGCAGGGAAGAUGAAUUG	20	5108
  BCL11A-4478	+	GGCGGCGGCGGCGGCGG	17	5109
  BCL11A-4479	+	GGCGGCGGCGGCGGCGGCGG	20	5110
  BCL11A-4480	+	GGCGGGCCGAGGGGAGG	17	5111
  BCL11A-4481	+	GGCUGCGGGGCGGGCGG	17	5112
  BCL11A-4482	+	GGCUGCGGGGCGGGCGGCGG	20	5113
  BCL11A-4483	+	GGGAGAGAAGAAAGGGG	17	5114
  BCL11A-4484	+	GGGAGGAAAGGGUGGGG	17	5115
  BCL11A-4485	+	GGGAGGGGCGGGCCGAG	17	5116
  BCL11A-4486	+	GGGAGGGGCGGGCCGAGGGG	20	5117
  BCL11A-4487	+	GGGAGGGGGAGGUGCGGGGC	20	5118
  BCL11A-4488	+	GGGAGGGGGCGCUGGGGCCG	20	5119
  BCL11A-4489	+	GGGAGGUGCGGGGCGGG	17	5120
  BCL11A-4490	+	GGGCCGAGGGGAGGGGGCGC	20	5121
  BCL11A-4491	+	GGGCGAGCAGGAGAGAA	17	5122
  BCL11A-4492	+	GGGCGGGCCGAGGGGAG	17	5123
  BCL11A-4493	+	GGGGAAGCUCACACCAA	17	5124
  BCL11A-4494	+	GGGGAGGGGCGGGCCGA	17	5125
  BCL11A-4495	+	GGGGAGGGGGAGGUGCG	17	5126
  BCL11A-4496	+	GGGGAGGGGGAGGUGCGGGG	20	5127
  BCL11A-4497	+	GGGGAGGUGCGGGGCGG	17	5128
  BCL11A-4498	−	GGGGCCGCGUCUGGCGUCCG	20	5129
  BCL11A-4499	+	GGGGCGGGCCGAGGGGA	17	5130
  BCL11A-4500	+	GGGGCGGGCGGCGGCGG	17	5131
  BCL11A-4501	+	GGGGCGGGCGGCGGCGGCGG	20	5132
  BCL11A-4502	+	GGGGGAGGGGCGGGCCG	17	5133
  BCL11A-4503	+	GGGGGAGGUGCGGGGCG	17	5134
  BCL11A-4504	+	GGGGGCGCUGGGGCCGC	17	5135
  BCL11A-4505	+	GGGGUGGCAGGGGUGGG	17	5136
  BCL11A-4506	+	GGGGUGGGAGGAAAGGG	17	5137
  BCL11A-4507	+	GGGGUGGGAGGAAAGGGUGG	20	5138
  BCL11A-4508	+	GGGGUUUGCCUUGCUUG	17	5139
  BCL11A-4509	+	GGGUGGGAGGAAAGGGU	17	5140
  BCL11A-4510	+	GGGUGGGAGGAAAGGGUGGG	20	5141
  BCL11A-4511	−	GGUAAAAGAGAUAAAGG	17	5142
  BCL11A-4512	+	GGUGGCAGGGGUGGGAGGAA	20	5143
  BCL11A-4513	+	GGUGGGAGGAAAGGGUG	17	5144
  BCL11A-4514	+	GGUGGGAGGAAAGGGUGGGG	20	5145
  BCL11A-4515	+	GGUUCCAGAUGGGAUGA	17	5146
  BCL11A-4516	−	GUAUUAUUUCUAAUUUAUUU	20	5147
  BCL11A-4517	−	GUCGAGGUAAAAGAGAUAAA	20	5148
  BCL11A-4518	+	GUGCGGGGAGGGGGAGGUGC	20	5149
  BCL11A-4519	+	GUGCGGGGCGGGGGGCUCCG	20	5150
  BCL11A-4520	+	GUGGCAGGGGUGGGAGGAAA	20	5151
  BCL11A-4521	+	GUGGCCGGGAGAGAAGAAAG	20	5152
  BCL11A-4522	+	GUGGGAGGAAAGGGUGG	17	5153
  BCL11A-4523	+	GUGGGCUGCGGGGCGGG	17	5154
  BCL11A-4524	+	GUGGGCUGCGGGGCGGGCGG	20	5155
  BCL11A-4525	−	GUGUGUGGGGGGGAGCA	17	5156

• Table 10D provides exemplary targeting domains for knocking down expression of the BCL11A gene according to forth tier parameters. The targeting domains bind between 500 bp upstream and 500 bp 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 500 bp upstream and 500 bp 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 10D
  4th Tier	DNA		Target Site	SEQ ID
  gRNA Name	Strand	Targeting Domain	Length	NO
  BCL11A-4526	+	AAAAAAAAAAAAAAAAAAAG	20	5157
  BCL11A-4527	+	AAAAAAAAAAAAAAAAAAGA	20	5158
  BCL11A-4528	+	AAAAAAAAAAAAAAAAG	17	5159
  BCL11A-4529	+	AAAAAAAAAAAAAAAGA	17	5160
  BCL11A-4530	+	AAAACAUGGGCAGGGCGAGC	20	5161
  BCL11A-4531	−	AAAACCCUCAUCCCAUC	17	5162
  BCL11A-4532	−	AAAACCUCCGAGAGUCG	17	5163
  BCL11A-4533	−	AAAAGCGAGGGGGAGAG	17	5164
  BCL11A-4534	−	AAAGCGAGGGGGAGAGA	17	5165
  BCL11A-4535	+	AAAGGGGUGGCAGGGGU	17	5166
  BCL11A-4536	+	AAAGGGGUGGCAGGGGUGGG	20	5167
  BCL11A-4537	+	AAAUAAUACAAAGAUGGCGC	20	5168
  BCL11A-4538	−	AACCCCAGCACUUAAGCAAA	20	5169
  BCL11A-4539	+	AACGUCAGGAGUCUGGA	17	5170
  BCL11A-4540	+	AAGAAAGGGGUGGCAGGGGU	20	5171
  BCL11A-4541	+	AAGAGACCAGGACAAGCCAA	20	5172
  BCL11A-4542	+	AAGCCAAUGGCCAGUGC	17	5173
  BCL11A-4543	−	AAGCGAGGGGGAGAGAG	17	5174
  BCL11A-4544	+	AAGUGCAUACACGGCAA	17	5175
  BCL11A-4545	+	AAUAAUACAAAGAUGGCGCA	20	5176
  BCL11A-4546	+	AAUACAAAGAUGGCGCA	17	5177
  BCL11A-4547	+	AAUGGACACACAUCAGGGGC	20	5178
  BCL11A-4548	+	AAUGGCCAGUGCGGGGA	17	5179
  BCL11A-4549	+	AAUGGUUCCAGAUGGGAUGA	20	5180
  BCL11A-4550	+	AAUUAAAUAAAAUUAAA	17	5181
  BCL11A-4551	+	AAUUAGAAAUAAUACAAAGA	20	5182
  BCL11A-4552	−	AAUUUAUUUUGGAUGUCAAA	20	5183
  BCL11A-4553	+	ACAAGCCAAUGGCCAGUGCG	20	5184
  BCL11A-4554	+	ACACACAAAACAUGGGC	17	5185
  BCL11A-4555	+	ACACCAAUGGACACACAUCA	20	5186
  BCL11A-4556	+	ACAUGGGCAGGGCGAGC	17	5187
  BCL11A-4557	+	ACCAAUGGACACACAUC	17	5188
  BCL11A-4558	−	ACCCCAGCACUUAAGCAAAC	20	5189
  BCL11A-4559	−	ACCCCUUUCUUCUCUCC	17	5190
  BCL11A-4560	+	ACGCCAGACGCGGCCCC	17	5191
  BCL11A-4561	+	ACGCCAGACGCGGCCCCCGG	20	5192
  BCL11A-4562	+	ACGCGGCCCCCGGGGGA	17	5193
  BCL11A-4563	+	ACGGCAAUGGUUCCAGA	17	5194
  BCL11A-4564	−	ACUAGAAGCAAAAGCGA	17	5195
  BCL11A-4565	−	ACUGAUGAAGAUAUUUUCUC	20	5196
  BCL11A-4566	−	ACUUGAACUUGCAGCUC	17	5197
  BCL11A-4567	−	ACUUGAACUUGCAGCUCAGG	20	5198
  BCL11A-4568	−	AGAAAAACCUCCGAGAGUCG	20	5199
  BCL11A-4569	+	AGAAGAAAGGGGUGGCA	17	5200
  BCL11A-4570	+	AGAAGGGGAGGAGGGAA	17	5201
  BCL11A-4571	+	AGACACACAAAACAUGGGCA	20	5202
  BCL11A-4572	+	AGACAUGGUGGGCUGCG	17	5203
  BCL11A-4573	+	AGACAUGGUGGGCUGCGGGG	20	5204
  BCL11A-4574	+	AGACCAGGACAAGCCAA	17	5205
  BCL11A-4575	+	AGACGCGGCCCCCGGGGGAG	20	5206
  BCL11A-4576	+	AGAGAAGAAAGGGGUGGCAG	20	5207
  BCL11A-4577	+	AGAGAAGGGGAGGAGGGAAG	20	5208
  BCL11A-4578	+	AGAGACACACAAAACAU	17	5209
  BCL11A-4579	+	AGAGAGAAGAGAGAUAG	17	5210
  BCL11A-4580	+	AGAGAGAGAAGAGAGAUAGA	20	5211
  BCL11A-4581	+	AGAGAGAGAGAUGAAAAAAA	20	5212
  BCL11A-4582	−	AGAGUCCGCGUGUGUGG	17	5213
  BCL11A-4583	−	AGCAAAAGCGAGGGGGAGAG	20	5214
  BCL11A-4584	+	AGCAGGAGAGAAGGGGAGGA	20	5215
  BCL11A-4585	+	AGCCAAUGGCCAGUGCG	17	5216
  BCL11A-4586	+	AGCCAAUGGCCAGUGCGGGG	20	5217
  BCL11A-4587	−	AGCCCCUGAUGUGUGUCCAU	20	5218
  BCL11A-4588	+	AGCGAGCGCCGCGGCGG	17	5219
  BCL11A-4589	+	AGCUGCAAGUUCAAGUG	17	5220
  BCL11A-4590	−	AGGACUAGAAGCAAAAGCGA	20	5221
  BCL11A-4591	+	AGGAGAGAAGGGGAGGA	17	5222
  BCL11A-4592	+	AGGGCGAGCAGGAGAGA	17	5223
  BCL11A-4593	+	AGGGGCGGGCCGAGGGG	17	5224
  BCL11A-4594	+	AGGGGCGGGCCGAGGGGAGG	20	5225
  BCL11A-4595	+	AGGGGGAGGUGCGGGGC	17	5226
  BCL11A-4596	+	AGGGGGAGGUGCGGGGCGGG	20	5227
  BCL11A-4597	+	AGGGGGCGCUGGGGCCG	17	5228
  BCL11A-4598	+	AGGGGUGGGAGGAAAGGGUG	20	5229
  BCL11A-4599	−	AGGUAAAAGAGAUAAAG	17	5230
  BCL11A-4600	−	AGUCCGCGUGUGUGGGG	17	5231
  BCL11A-4601	−	AGUCGAGGUAAAAGAGAUAA	20	5232
  BCL11A-4602	+	AGUGCGGGGAGGGGGAGGUG	20	5233
  BCL11A-4603	+	AGUGGCCGCAGCGAGCGCCG	20	5234
  BCL11A-4604	+	AUAAUUAUUAUUACUAUUAU	20	5235
  BCL11A-4605	+	AUCUCUUUUACCUCGACUCU	20	5236
  BCL11A-4606	+	AUGGCCAGUGCGGGGAG	17	5237
  BCL11A-4607	+	AUGGUGGGCUGCGGGGC	17	5238
  BCL11A-4608	+	AUGGUGGGCUGCGGGGCGGG	20	5239
  BCL11A-4609	+	AUUAUUAUUACUAUUAU	17	5240
  BCL11A-4610	−	AUUUUAGAGUCCGCGUGUGU	20	5241
  BCL11A-4611	−	CAAAAGCGAGGGGGAGAGAG	20	5242
  BCL11A-4612	+	CAAAAGUGCAUACACGGCAA	20	5243
  BCL11A-4613	+	CAAGCCAAUGGCCAGUG	17	5244
  BCL11A-4614	+	CAAUGGACACACAUCAG	17	5245
  BCL11A-4615	+	CAAUGGCCAGUGCGGGG	17	5246
  BCL11A-4616	+	CAAUGGCCAGUGCGGGGAGG	20	5247
  BCL11A-4617	+	CAAUGGUUCCAGAUGGGAUG	20	5248
  BCL11A-4618	+	CACACAAAACAUGGGCA	17	5249
  BCL11A-4619	+	CACACCAAUGGACACACAUC	20	5250
  BCL11A-4620	+	CACCAAUGGACACACAUCAG	20	5251
  BCL11A-4621	−	CACCGCCGCGGCGCUCGCUG	20	5252
  BCL11A-4622	−	CACUGGCCAUUGGCUUGUCC	20	5253
  BCL11A-4623	−	CACUUGAACUUGCAGCUCAG	20	5254
  BCL11A-4624	+	CAGACGCGGCCCCCGGGGGA	20	5255
  BCL11A-4625	+	CAGAGACACACAAAACA	17	5256
  BCL11A-4626	−	CAGGACUAGAAGCAAAAGCG	20	5257
  BCL11A-4627	+	CAGGAGAGAAGGGGAGG	17	5258
  BCL11A-4628	+	CAGGGAAGAUGAAUUGU	17	5259
  BCL11A-4629	+	CAGGGCGAGCAGGAGAGAAG	20	5260
  BCL11A-4630	+	CAGGGGUGGGAGGAAAGGGU	20	5261
  BCL11A-4631	+	CAUGGUGGGCUGCGGGG	17	5262
  BCL11A-4632	+	CCAAUGGACACACAUCA	17	5263
  BCL11A-4633	+	CCAAUGGCCAGUGCGGGGAG	20	5264
  BCL11A-4634	+	CCAGACGCGGCCCCCGG	17	5265
  BCL11A-4635	+	CCAGACGCGGCCCCCGGGGG	20	5266
  BCL11A-4636	−	CCAGCACUUAAGCAAAC	17	5267
  BCL11A-4637	−	CCAGCGCCCCCUCCCCU	17	5268
  BCL11A-4638	+	CCAGUGCGGGGAGGGGG	17	5269
  BCL11A-4639	−	CCCAGCACUUAAGCAAA	17	5270
  BCL11A-4640	−	CCCCCGGGGGCCGCGUC	17	5271
  BCL11A-4641	−	CCCCUCCCCGCACUGGCCAU	20	5272
  BCL11A-4642	+	CCCGGGGGAGGGGCGGGCCG	20	5273
  BCL11A-4643	+	CCCGUUUGCUUAAGUGC	17	5274
  BCL11A-4644	−	CCCUCGGCCCGCCCCUCCCC	20	5275
  BCL11A-4645	−	CCCUGAUGUGUGUCCAU	17	5276
  BCL11A-4646	+	CCGAGGGGAGGGGGCGC	17	5277
  BCL11A-4647	−	CCGCGUGUGUGGGGGGGAGC	20	5278
  BCL11A-4648	+	CCGGGGGAGGGGCGGGCCGA	20	5279
  BCL11A-4649	+	CCGUUUGCUUAAGUGCU	17	5280
  BCL11A-4650	−	CCUCCCCCGGGGGCCGCGUC	20	5281
  BCL11A-4651	−	CCUCCCCCUCCCCGCAC	17	5282
  BCL11A-4652	−	CCUCGGCCCGCCCCUCCCCC	20	5283
  BCL11A-4653	+	CCUGCUCCCCCCCACACACG	20	5284
  BCL11A-4654	+	CGAGACAUGGUGGGCUG	17	5285
  BCL11A-4655	+	CGAGCGCCGCGGCGGUGGCG	20	5286
  BCL11A-4656	+	CGAGGGGAGGGGGCGCU	17	5287
  BCL11A-4657	−	CGAGGUAAAAGAGAUAA	17	5288
  BCL11A-4658	−	CGAGGUAAAAGAGAUAAAGG	20	5289
  BCL11A-4659	−	CGCACUUGAACUUGCAGCUC	20	5290
  BCL11A-4660	+	CGCAGCGAGCGCCGCGG	17	5291
  BCL11A-4661	+	CGCAGCGAGCGCCGCGGCGG	20	5292
  BCL11A-4662	+	CGCCAGACGCGGCCCCC	17	5293
  BCL11A-4663	−	CGCCGCGGCGCUCGCUG	17	5294
  BCL11A-4664	+	CGCCGCGGCGGUGGCGUGGC	20	5295
  BCL11A-4665	+	CGCGGCCCCCGGGGGAG	17	5296
  BCL11A-4666	+	CGCGGCCCCCGGGGGAGGGG	20	5297
  BCL11A-4667	+	CGCGGCGGUGGCGUGGC	17	5298
  BCL11A-4668	−	CGCGUGUGUGGGGGGGAGCA	20	5299
  BCL11A-4669	+	CGGCAAUGGUUCCAGAU	17	5300
  BCL11A-4670	−	CGGCCACGCCACCGCCG	17	5301
  BCL11A-4671	−	CGGCCCGCCCCUCCCCC	17	5302
  BCL11A-4672	+	CGGCGAGACAUGGUGGGCUG	20	5303
  BCL11A-4673	+	CGGCGGCGGCGGGCGGACGA	20	5304
  BCL11A-4674	+	CGGCGGCGGGCGGACGA	17	5305
  BCL11A-4675	+	CGGGGAGGGGGAGGUGC	17	5306
  BCL11A-4676	+	CGGGGCGGGGGGCUCCG	17	5307
  BCL11A-4677	+	CGGGGGAGGGGCGGGCCGAG	20	5308
  BCL11A-4678	+	CGUGGCCGGGAGAGAAGAAA	20	5309
  BCL11A-4679	−	CGUGUGUGGGGGGGAGC	17	5310
  BCL11A-4680	+	CGUUUGCUUAAGUGCUG	17	5311
  BCL11A-4681	−	CUAGAAGCAAAAGCGAG	17	5312
  BCL11A-4682	−	CUCCCCGCACUGGCCAU	17	5313
  BCL11A-4683	−	CUCGGCCCGCCCCUCCCCCG	20	5314
  BCL11A-4684	+	CUGAGCUGCAAGUUCAAGUG	20	5315
  BCL11A-4685	+	CUGCGAACUUGAACGUC	17	5316
  BCL11A-4686	+	CUGGACAUGAAAAAGAGACC	20	5317
  BCL11A-4687	+	CUGUCUCAAAAGUGCAUACA	20	5318
  BCL11A-4688	+	CUUGAACGUCAGGAGUC	17	5319
  BCL11A-4689	−	CUUGAACUUGCAGCUCA	17	5320
  BCL11A-4690	−	CUUGAACUUGCAGCUCAGGG	20	5321
  BCL11A-4691	+	CUUGCGGCGAGACAUGG	17	5322
  BCL11A-4692	+	GUUCACAUCGGGAGAGC	17	5323
  BCL11A-4693	+	UAAUACAAAGAUGGCGC	17	5324
  BCL11A-4694	+	UAAUUAUUAUUACUAUUAUU	20	5325
  BCL11A-4695	+	UACACGGCAAUGGUUCCAGA	20	5326
  BCL11A-4696	+	UAGAAAUAAUACAAAGA	17	5327
  BCL11A-4697	−	UAGAAGCAAAAGCGAGG	17	5328
  BCL11A-4698	−	UAGAGUCCGCGUGUGUG	17	5329
  BCL11A-4699	−	UAGAGUCCGCGUGUGUGGGG	20	5330
  BCL11A-4700	−	UCCCGGCCACGCCACCGCCG	20	5331
  BCL11A-4701	+	UCCCGUUUGCUUAAGUGCUG	20	5332
  BCL11A-4702	+	UCCCUGCGAACUUGAACGUC	20	5333
  BCL11A-4703	−	UCGAGGUAAAAGAGAUAAAG	20	5334
  BCL11A-4704	−	UCGGCCCGCCCCUCCCC	17	5335
  BCL11A-4705	−	UCGGCCCGCCCCUCCCCCGG	20	5336
  BCL11A-4706	+	UCUCAAAAGUGCAUACA	17	5337
  BCL11A-4707	−	UCUCCUUCUUUCUAACC	17	5338
  BCL11A-4708	+	UCUUUUACCUCGACUCU	17	5339
  BCL11A-4709	−	UGAACUUGCAGCUCAGG	17	5340
  BCL11A-4710	−	UGCGGCCACUGGUGAGCCCG	20	5341
  BCL11A-4711	+	UGCGGGGAGGGGGAGGUGCG	20	5342
  BCL11A-4712	+	UGCGGGGCGGGCGGCGG	17	5343
  BCL11A-4713	+	UGCGGGGCGGGCGGCGGCGG	20	5344
  BCL11A-4714	−	UGCUUAAAAAAAAGCCAUGA	20	5345
  BCL11A-4715	+	UGGCCAGUGCGGGGAGG	17	5346
  BCL11A-4716	+	UGGCCAGUGCGGGGAGGGGG	20	5347
  BCL11A-4717	−	UGGCCAUUGGCUUGUCC	17	5348
  BCL11A-4718	+	UGGCCGGGAGAGAAGAA	17	5349
  BCL11A-4719	+	UGGGAGGAAAGGGUGGG	17	5350
  BCL11A-4720	+	UGGGGCCGCGGGCUCACCAG	20	5351
  BCL11A-4721	+	UGGUUCCAGAUGGGAUG	17	5352
  BCL11A-4722	−	UUAAAAAAAAGCCAUGA	17	5353
  BCL11A-4723	−	UUAGAGUCCGCGUGUGUGGG	20	5354
  BCL11A-4724	+	UUAUUAUUACUAUUAUU	17	5355
  BCL11A-4725	−	UUAUUUCUAAUUUAUUU	17	5356
  BCL11A-4726	−	UUAUUUUGGAUGUCAAA	17	5357
  BCL11A-4727	+	UUCACAUCGGGAGAGCC	17	5358
  BCL11A-4728	+	UUCCCGUUUGCUUAAGUGCU	20	5359
  BCL11A-4729	+	UUGAACGUCAGGAGUCUGGA	20	5360
  BCL11A-4730	−	UUGAACUUGCAGCUCAG	17	5361
  BCL11A-4731	+	UUGCUUGCGGCGAGACAUGG	20	5362
  BCL11A-4732	+	UUGUGGGAGAGCCGUCA	17	5363
  BCL11A-4733	−	UUUUAGAGUCCGCGUGUGUG	20	5364

• Table 11A provides exemplary targeting domains for knocking down expression of the BCL11A gene according to first tier parameters. The targeting domains bind between 500 bp upstream and 500 bp 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 500 bp upstream and 500 bp 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 11A
  1st Tier	DNA		Target Site	SEQ ID
  gRNA Name	Strand	Targeting Domain	Length	NO
  BCL11A-4734	+	GACGACGGCUCGGUUCACAU	20	6365
  BCL11A-4735	+	GACGGCUCGGUUCACAU	17	6366
  BCL11A-4736	+	GACGGCUCGGUUCACAUCGG	20	6367
  BCL11A-4737	+	GACGUGACGUCCCUGCGAAC	20	6368
  BCL11A-4738	+	GCGGACGUGACGUCCCU	17	6369
  BCL11A-4739	+	GGACGACGGCUCGGUUCACA	20	6370
  BCL11A-4740	−	GGACGUCACGUCCGCAC	17	6371
  BCL11A-4741	+	GGCUCGGUUCACAUCGG	17	6372
  BCL11A-4742	−	GGCUCUCCCGAUGUGAA	17	6373
  BCL11A-4743	+	GGUUCACAUCGGGAGAG	17	6374
  BCL11A-4744	+	GUCCCUGCGAACUUGAACGU	20	6375
  BCL11A-4745	+	GUGACGUCCCUGCGAAC	17	6376

• Table 11B provides exemplary targeting domains for knocking down expression of the BCL11A gene according to second tier parameters. The targeting domains bind between 500 bp upstream and 500 bp 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 500 bp upstream and 500 bp 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 11B
  2nd Tier	DNA		Target Site	SEQ ID
  gRNA Name	Strand	Targeting Domain	Length	NO
  BCL11A-4746	+	ACGACGGCUCGGUUCACAUC	20	6377
  BCL11A-4747	−	ACGAGAGCGCGCAGGAC	17	6378
  BCL11A-4748	+	ACGGCUCGGUUCACAUC	17	6379
  BCL11A-4749	+	AGUGCGGACGUGACGUCCCU	20	6380
  BCL11A-4750	−	AUCACGAGAGCGCGCAGGAC	20	6381
  BCL11A-4751	−	CAGGGACGUCACGUCCGCAC	20	6382
  BCL11A-4752	+	CAUCGGGAGAGCCGGGU	17	6383
  BCL11A-4753	−	CCCGGCUCUCCCGAUGUGAA	20	6384
  BCL11A-4754	+	CCUGCGAACUUGAACGU	17	6385
  BCL11A-4755	+	CGACGGCUCGGUUCACA	17	6386
  BCL11A-4756	+	CUCGGUUCACAUCGGGAGAG	20	6387
  BCL11A-4757	+	CUGCGAACUUGAACGUC	17	6388
  BCL11A-4758	+	UCACAUCGGGAGAGCCGGGU	20	6389
  BCL11A-4759	+	UCCCUGCGAACUUGAACGUC	20	6390

• Table 11C provides exemplary targeting domains for knocking down expression of the BCL11A gene according to third tier parameters. The targeting domains bind between 500 bp upstream and 500 bp 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 500 bp upstream and 500 bp 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 11C
  3rd Tier	DNA		Target Site	SEQ ID
  gRNA Name	Strand	Targeting Domain	Length	NO
  BCL11A-4760	−	GAAAAAACCCUCAUCCCAUC	20	6391
  BCL11A-4761	+	GAAAGAAGGAGACUCCA	17	6392
  BCL11A-4762	+	GAAAGGGGUGGCAGGGG	17	6393
  BCL11A-4763	+	GAAAGGGGUGGCAGGGGUGG	20	6394
  BCL11A-4764	+	GAAAUAAUACAAAGAUGGCG	20	6395
  BCL11A-4765	+	GAACGUCAGGAGUCUGG	17	6396
  BCL11A-4766	+	GAAGAAAGGGGUGGCAGGGG	20	6397
  BCL11A-4767	+	GAAGAGAGAUAGAGGGA	17	6398
  BCL11A-4768	−	GAAGCAAAAGCGAGGGG	17	6399
  BCL11A-4769	+	GAAGGGGAGGAGGGAAG	17	6400
  BCL11A-4770	+	GACAAGCCAAUGGCCAGUGC	20	6401
  BCL11A-4771	+	GACACACAAAACAUGGG	17	6402
  BCL11A-4772	+	GACGCCAGACGCGGCCC	17	6403
  BCL11A-4773	+	GACGCCAGACGCGGCCCCCG	20	6404
  BCL11A-4774	+	GACGCGGCCCCCGGGGG	17	6405
  BCL11A-4775	−	GACUAGAAGCAAAAGCG	17	6406
  BCL11A-4776	−	GACUAGAAGCAAAAGCGAGG	20	6407
  BCL11A-4777	+	GACUCUCGGAGGUUUUUCUC	20	6408
  BCL11A-4778	+	GAGAAGAAAGGGGUGGC	17	6409
  BCL11A-4779	+	GAGAAGAGAGAUAGAGG	17	6410
  BCL11A-4780	+	GAGAAGGGGAGGAGGGA	17	6411
  BCL11A-4781	+	GAGACAUGGUGGGCUGCGGG	20	6412
  BCL11A-4782	+	GAGAGAAGAGAGAUAGA	17	6413
  BCL11A-4783	+	GAGAGAAGGGGAGGAGGGAA	20	6414
  BCL11A-4784	+	GAGAGAGAAGAGAGAUA	17	6415
  BCL11A-4785	+	GAGAGAGAGAAGAGAGA	17	6416
  BCL11A-4786	+	GAGAGAGAGAAGAGAGAUAG	20	6417
  BCL11A-4787	+	GAGAGAGAGAGAGAGAG	17	6418
  BCL11A-4788	+	GAGAGAUAGAGGGAGAGAGA	20	6419
  BCL11A-4789	+	GAGAUAGAGGGAGAGAGAGA	20	6420
  BCL11A-4790	+	GAGCAGGAGAGAAGGGG	17	6421
  BCL11A-4791	+	GAGCAGGAGAGAAGGGGAGG	20	6422
  BCL11A-4792	+	GAGCCGGGUUAGAAAGA	17	6423
  BCL11A-4793	+	GAGCUGCAAGUUCAAGU	17	6424
  BCL11A-4794	+	GAGGGAGAGAGAGAGAA	17	6425
  BCL11A-4795	+	GAGGGGCGGGCCGAGGG	17	6426
  BCL11A-4796	+	GAGGGGGAGGUGCGGGG	17	6427
  BCL11A-4797	+	GAGGGGGCGCUGGGGCC	17	6428
  BCL11A-4798	−	GAGGUAAAAGAGAUAAA	17	6429
  BCL11A-4799	−	GAGUCCGCGUGUGUGGG	17	6430
  BCL11A-4800	−	GAGUCGAGGUAAAAGAGAUA	20	6431
  BCL11A-4801	+	GAUAGAGGGAGAGAGAGAGA	20	6432
  BCL11A-4802	−	GAUGAAGAUAUUUUCUC	17	6433
  BCL11A-4803	−	GAUGUCAAAAGGCACUG	17	6434
  BCL11A-4804	−	GAUGUGUGUCCAUUGGU	17	6435
  BCL11A-4805	+	GCAAUGGUUCCAGAUGGGAU	20	6436
  BCL11A-4806	−	GCACUUGAACUUGCAGCUCA	20	6437
  BCL11A-4807	−	GCAGGACUAGAAGCAAAAGC	20	6438
  BCL11A-4808	+	GCAGGAGAGAAGGGGAG	17	6439
  BCL11A-4809	+	GCAGGGAAGAUGAAUUG	17	6440
  BCL11A-4810	+	GCAGGGAAGAUGAAUUGUGG	20	6441
  BCL11A-4811	+	GCAGGGCGAGCAGGAGAGAA	20	6442
  BCL11A-4812	+	GCAGGGGUGGGAGGAAAGGG	20	6443
  BCL11A-4813	−	GCAUUUUUAAAUUUUUC	17	6444
  BCL11A-4814	+	GCCAAUGGCCAGUGCGGGGA	20	6445
  BCL11A-4815	+	GCCAGACGCGGCCCCCG	17	6446
  BCL11A-4816	+	GCCAGACGCGGCCCCCGGGG	20	6447
  BCL11A-4817	+	GCCCCCGGGGGAGGGGCGGG	20	6448
  BCL11A-4818	+	GCCGAGGGGAGGGGGCG	17	6449
  BCL11A-4819	+	GCCGCGGCGGUGGCGUGGCC	20	6450
  BCL11A-4820	−	GCCGCGUCUGGCGUCCG	17	6451
  BCL11A-4821	+	GCGAGACAUGGUGGGCU	17	6452
  BCL11A-4822	−	GCGCAGGACUAGAAGCAAAA	20	6453
  BCL11A-4823	+	GCGCAGGGAAGAUGAAUUGU	20	6454
  BCL11A-4824	+	GCGCCGCGGCGGUGGCGUGG	20	6455
  BCL11A-4825	+	GCGGACGCCAGACGCGGCCC	20	6456
  BCL11A-4826	+	GCGGCGAGACAUGGUGGGCU	20	6457
  BCL11A-4827	+	GCGGCGGUGGCGUGGCC	17	6458
  BCL11A-4828	+	GCGGGGAGGGGGAGGUG	17	6459
  BCL11A-4829	+	GCGGGGCGGGGGGCUCC	17	6460
  BCL11A-4830	+	GCGUGGCCGGGAGAGAAGAA	20	6461
  BCL11A-4831	−	GCGUGUGUGGGGGGGAG	17	6462
  BCL11A-4832	+	GCUCACCAGUGGCCGCA	17	6463
  BCL11A-4833	−	GCUCGCUGCGGCCACUG	17	6464
  BCL11A-4834	+	GCUGGACAUGAAAAAGAGAC	20	6465
  BCL11A-4835	+	GCUUGCGGCGAGACAUG	17	6466
  BCL11A-4836	−	GGAAAAAACCCUCAUCCCAU	20	6467
  BCL11A-4837	+	GGAAGGGGAAGCUCACACCA	20	6468
  BCL11A-4838	+	GGACAAGCCAAUGGCCAGUG	20	6469
  BCL11A-4839	+	GGACAUGAAAAAGAGAC	17	6470
  BCL11A-4840	+	GGACGCCAGACGCGGCCCCC	20	6471
  BCL11A-4841	−	GGACUAGAAGCAAAAGC	17	6472
  BCL11A-4842	−	GGACUAGAAGCAAAAGCGAG	20	6473
  BCL11A-4843	+	GGAGAGAAGAAAGGGGUGGC	20	6474
  BCL11A-4844	+	GGAGAGAAGGGGAGGAGGGA	20	6475
  BCL11A-4845	+	GGAGAGAGAGAGAAGAGAGA	20	6476
  BCL11A-4846	+	GGAGAGCCGGGUUAGAAAGA	20	6477
  BCL11A-4847	+	GGAGGGGCGGGCCGAGGGGA	20	6478
  BCL11A-4848	+	GGAGGGGGAGGUGCGGG	17	6479
  BCL11A-4849	+	GGAGGGGGAGGUGCGGGGCG	20	6480
  BCL11A-4850	+	GGCAGGGCGAGCAGGAGAGA	20	6481
  BCL11A-4851	+	GGCAGGGGUGGGAGGAAAGG	20	6482
  BCL11A-4852	−	GGCCGCGUCUGGCGUCC	17	6483
  BCL11A-4853	+	GGCGAGCAGGAGAGAAG	17	6484
  BCL11A-4854	+	GGCGAGCAGGAGAGAAGGGG	20	6485
  BCL11A-4855	+	GGCGCAGGGAAGAUGAAUUG	20	6486
  BCL11A-4856	−	GGCGCUCGCUGCGGCCACUG	20	6487
  BCL11A-4857	+	GGCGGCGGCGGCGGCGG	17	6488
  BCL11A-4858	+	GGCGGCGGCGGCGGCGGCGG	20	6489
  BCL11A-4859	+	GGCGGUGGCGUGGCCGG	17	6490
  BCL11A-4860	+	GGCGUGGCCGGGAGAGAAGA	20	6491
  BCL11A-4861	+	GGGAAGAUGAAUUGUGG	17	6492
  BCL11A-4862	+	GGGAGAGAAGAAAGGGGUGG	20	6493
  BCL11A-4863	+	GGGAGAGCCGGGUUAGA	17	6494
  BCL11A-4864	+	GGGAGAGCCGGGUUAGAAAG	20	6495
  BCL11A-4865	+	GGGAGGAAAGGGUGGGG	17	6496
  BCL11A-4866	+	GGGAGGGGCGGGCCGAG	17	6497
  BCL11A-4867	+	GGGAGGGGCGGGCCGAGGGG	20	6498
  BCL11A-4868	+	GGGAGGGGGAGGUGCGGGGC	20	6499
  BCL11A-4869	+	GGGCAGGGCGAGCAGGA	17	6500
  BCL11A-4870	+	GGGCAGGGCGAGCAGGAGAG	20	6501
  BCL11A-4871	+	GGGCCGAGGGGAGGGGGCGC	20	6502
  BCL11A-4872	+	GGGCGAGCAGGAGAGAA	17	6503
  BCL11A-4873	+	GGGCGAGCAGGAGAGAAGGG	20	6504
  BCL11A-4874	+	GGGGAGGGGCGGGCCGA	17	6505
  BCL11A-4875	+	GGGGAGGGGCGGGCCGAGGG	20	6506
  BCL11A-4876	+	GGGGAGGGGGAGGUGCGGGG	20	6507
  BCL11A-4877	+	GGGGAGGGGGCGCUGGGGCC	20	6508
  BCL11A-4878	−	GGGGCCGCGUCUGGCGUCCG	20	6509
  BCL11A-4879	+	GGGGCGGGCCGAGGGGA	17	6510
  BCL11A-4880	+	GGGGGAGGGGCGGGCCG	17	6511
  BCL11A-4881	+	GGGGGAGGUGCGGGGCG	17	6512
  BCL11A-4882	−	GGGGGCCGCGUCUGGCGUCC	20	6513
  BCL11A-4883	+	GGGGUGGCAGGGGUGGG	17	6514
  BCL11A-4884	+	GGGGUGGGAGGAAAGGG	17	6515
  BCL11A-4885	+	GGGGUGGGAGGAAAGGGUGG	20	6516
  BCL11A-4886	+	GGGUGGCAGGGGUGGGAGGA	20	6517
  BCL11A-4887	+	GGGUGGGAGGAAAGGGU	17	6518
  BCL11A-4888	+	GGGUGGGAGGAAAGGGUGGG	20	6519
  BCL11A-4889	−	GGUAAAAGAGAUAAAGG	17	6520
  BCL11A-4890	+	GGUGCGGGGCGGGGGGCUCC	20	6521
  BCL11A-4891	+	GGUGGGAGGAAAGGGUG	17	6522
  BCL11A-4892	+	GGUGGGAGGAAAGGGUGGGG	20	6523
  BCL11A-4893	+	GGUUAGAAAGAAGGAGACUC	20	6524
  BCL11A-4894	+	GGUUUGCCUUGCUUGCG	17	6525
  BCL11A-4895	−	GUCGAGGUAAAAGAGAUAAA	20	6526
  BCL11A-4896	+	GUGGCCGGGAGAGAAGA	17	6527
  BCL11A-4897	+	GUGGGAGGAAAGGGUGG	17	6528

• Table 11D provides exemplary targeting domains for knocking down expression of the BCL11A gene according to forth tier parameters. The targeting domains bind between 500 bp upstream and 500 bp 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 500 bp upstream and 500 bp 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 11D
  4th Tier

  	DNA		Target Site	SEQ ID
  gRNA Name	Strand	Targeting Domain	Length	NO
  BCL11A-4898	+	AAAAAAAAAAAAAAAAA	17	6529
  BCL11A-4899	+	AAAAAAAAAAAAAAAAAAAA	20	6530
  BCL11A-4900	+	AAAAAAAAAAAAAAAAAAAG	20	6531
  BCL11A-4901	+	AAAAAAAAAAAAAAAAAAGA	20	6532
  BCL11A-4902	+	AAAAAAAAAAAAAAAAG	17	6533
  BCL11A-4903	+	AAAAAAAAAAAAAAAAGAGG	20	6534
  BCL11A-4904	+	AAAAAAAAAAAAAAAGA	17	6535
  BCL11A-4905	+	AAAAAAAAAAAAAAGAGGGA	20	6536
  BCL11A-4906	+	AAAAAAAAAAAAAGAGG	17	6537
  BCL11A-4907	+	AAAAAAAAAAAAGAGGGAGA	20	6538
  BCL11A-4908	+	AAAAAAAAAAAGAGGGA	17	6539
  BCL11A-4909	+	AAAAAAAAAAGAGGGAGAGA	20	6540
  BCL11A-4910	+	AAAAAAAAAGAGGGAGA	17	6541
  BCL11A-4911	+	AAAAAAAAGAGGGAGAGAGA	20	6542
  BCL11A-4912	+	AAAAAAAGAGGGAGAGA	17	6543
  BCL11A-4913	+	AAAAAAUGGCAAAAGCCCCC	20	6544
  BCL11A-4914	-	AAAAACCCUCAUCCCAU	17	6545
  BCL11A-4915	+	AAAAAGAGGGAGAGAGA	17	6546
  BCL11A-4916	+	AAAAAGAGGGAGAGAGAGAG	20	6547
  BCL11A-4917	+	AAAACAUGGGCAGGGCGAGC	20	6548
  BCL11A-4918	-	AAAACCCUCAUCCCAUC	17	6549
  BCL11A-4919	-	AAAAGCGAGGGGGAGAG	17	6550
  BCL11A-4920	-	AAACCCCAGCACUUAAGCAA	20	6551
  BCL11A-4921	+	AAAGAGGGAGAGAGAGAGAA	20	6552
  BCL11A-4922	+	AAAGGGGUGGCAGGGGU	17	6553
  BCL11A-4923	+	AAAGGGGUGGCAGGGGUGGG	20	6554
  BCL11A-4924	+	AAAUAAUACAAAGAUGGCGC	20	6555
  BCL11A-4925	+	AAAUGGCAAAAGCCCCC	17	6556
  BCL11A-4926	+	AACAUGGGCAGGGCGAG	17	6557
  BCL11A-4927	+	AACAUGGGCAGGGCGAGCAG	20	6558
  BCL11A-4928	-	AACCCCAGCACUUAAGCAAA	20	6559
  BCL11A-4929	-	AACCCGGCUCUCCCGAU	17	6560
  BCL11A-4930	+	AAGAAAGGGGUGGCAGGGGU	20	6561
  BCL11A-4931	+	AAGAGAGAUAGAGGGAGAGA	20	6562
  BCL11A-4932	+	AAGAGGGAGAGAGAGAG	17	6563
  BCL11A-4933	+	AAGAUGGCGCAGGGAAG	17	6564
  BCL11A-4934	-	AAGCAAAAGCGAGGGGGAGA	20	6565
  BCL11A-4935	+	AAGCCAAUGGCCAGUGC	17	6566
  BCL11A-4936	+	AAGCCAAUGGCCAGUGCGGG	20	6567
  BCL11A-4937	-	AAUAAUAAUUAUUAAUAAUC	20	6568
  BCL11A-4938	+	AAUAAUACAAAGAUGGCGCA	20	6569
  BCL11A-4939	-	AAUAAUUAUUAAUAAUC	17	6570
  BCL11A-4940	+	AAUAAUUAUUAUUACUAUUA	20	6571
  BCL11A-4941	+	AAUACAAAGAUGGCGCA	17	6572
  BCL11A-4942	+	AAUGGCCAGUGCGGGGA	17	6573
  BCL11A-4943	+	AAUUAUUAUUACUAUUA	17	6574
  BCL11A-4944	+	AAUUCCCGUUUGCUUAAGUG	20	6575
  BCL11A-4945	+	ACAAAGAUGGCGCAGGGAAG	20	6576
  BCL11A-4946	+	ACAAGCCAAUGGCCAGU	17	6577
  BCL11A-4947	+	ACAAGCCAAUGGCCAGUGCG	20	6578
  BCL11A-4948	+	ACACACAAAACAUGGGCAGG	20	6579
  BCL11A-4949	+	ACACACAUCAGGGGCUGGAC	20	6580
  BCL11A-4950	+	ACAGAGACACACAAAAC	17	6581
  BCL11A-4951	+	ACAUGGGCAGGGCGAGC	17	6582
  BCL11A-4952	+	ACAUGGUGGGCUGCGGG	17	6583
  BCL11A-4953	+	ACCAAUGGACACACAUC	17	6584
  BCL11A-4954	-	ACCCCAGCACUUAAGCAAAC	20	6585
  BCL11A-4955	-	ACCUCCGAGAGUCGAGGUAA	20	6586
  BCL11A-4956	-	ACGAGAAAAACCUCCGAGAG	20	6587
  BCL11A-4957	+	ACGCCAGACGCGGCCCC	17	6588
  BCL11A-4958	+	ACGCCAGACGCGGCCCCCGG	20	6589
  BCL11A-4959	+	ACGCGGCCCCCGGGGGAGGG	20	6590
  BCL11A-4960	+	ACGGCAAUGGUUCCAGA	17	6591
  BCL11A-4961	+	ACGUCAGGAGUCUGGAUGGA	20	6592
  BCL11A-4962	-	ACUAGAAGCAAAAGCGA	17	6593
  BCL11A-4963	+	ACUAUUAUUGGGUUACUUAC	20	6594
  BCL11A-4964	-	ACUCCUGACGUUCAAGUUCG	20	6595
  BCL11A-4965	-	ACUGAUGAAGAUAUUUUCUC	20	6596
  BCL11A-4966	+	ACUUGAACGUCAGGAGU	17	6597
  BCL11A-4967	-	ACUUGAACUUGCAGCUC	17	6598
  BCL11A-4968	-	AGAAAAACCUCCGAGAG	17	6599
  BCL11A-4969	+	AGAAAGGGGUGGCAGGG	17	6600
  BCL11A-4970	+	AGAAGAAAGGGGUGGCAGGG	20	6601
  BCL11A-4971	+	AGAAGAGAGAUAGAGGGAGA	20	6602
  BCL11A-4972	-	AGAAGCAAAAGCGAGGGGGA	20	6603
  BCL11A-4973	+	AGAAGGGGAGGAGGGAA	17	6604
  BCL11A-4974	+	AGACGCGGCCCCCGGGG	17	6605
  BCL11A-4975	+	AGAGAAGAAAGGGGUGG	17	6606
  BCL11A-4976	+	AGAGAAGAGAGAUAGAGGGA	20	6607
  BCL11A-4977	+	AGAGAAGGGGAGGAGGG	17	6608
  BCL11A-4978	+	AGAGAAGGGGAGGAGGGAAG	20	6609
  BCL11A-4979	+	AGAGACACACAAAACAUGGG	20	6610
  BCL11A-4980	+	AGAGAGAAGAGAGAUAG	17	6611
  BCL11A-4981	+	AGAGAGAAGAGAGAUAGAGG	20	6612
  BCL11A-4982	+	AGAGAGAGAAGAGAGAUAGA	20	6613
  BCL11A-4983	+	AGAGAGAGAGAAGAGAGAUA	20	6614
  BCL11A-4984	+	AGAGAGAUAGAGGGAGA	17	6615
  BCL11A-4985	+	AGAGAUAGAGGGAGAGA	17	6616
  BCL11A-4986	+	AGAGCCGGGUUAGAAAG	17	6617
  BCL11A-4987	+	AGAGGGAGAGAGAGAGA	17	6618
  BCL11A-4988	-	AGAGUCCGCGUGUGUGG	17	6619
  BCL11A-4989	+	AGAUAGAGGGAGAGAGA	17	6620
  BCL11A-4990	-	AGCAAAAGCGAGGGGGA	17	6621
  BCL11A-4991	-	AGCAAAAGCGAGGGGGAGAG	20	6622
  BCL11A-4992	+	AGCAGGAGAGAAGGGGAGGA	20	6623
  BCL11A-4993	+	AGCCAAUGGCCAGUGCG	17	6624
  BCL11A-4994	+	AGCCAAUGGCCAGUGCGGGG	20	6625
  BCL11A-4995	+	AGGACAAGCCAAUGGCCAGU	20	6626
  BCL11A-4996	-	AGGACUAGAAGCAAAAGCGA	20	6627
  BCL11A-4997	+	AGGAGAGAAGGGGAGGA	17	6628
  BCL11A-4998	+	AGGAGAGAAGGGGAGGAGGG	20	6629
  BCL11A-4999	+	AGGGAGAGAGAGAGAGAGAG	20	6630
  BCL11A-5000	+	AGGGCGAGCAGGAGAGA	17	6631
  BCL11A-5001	+	AGGGGAAGCUCACACCA	17	6632
  BCL11A-5002	+	AGGGGCGGGCCGAGGGG	17	6633
  BCL11A-5003	+	AGGGGCUGGACAUGAAA	17	6634
  BCL11A-5004	+	AGGGGGAGGUGCGGGGC	17	6635
  BCL11A-5005	+	AGGGGUGGCAGGGGUGG	17	6636
  BCL11A-5006	+	AGGGGUGGGAGGAAAGG	17	6637
  BCL11A-5007	+	AGGGGUGGGAGGAAAGGGUG	20	6638
  BCL11A-5008	-	AGGUAAAAGAGAUAAAG	17	6639
  BCL11A-5009	-	AGUCCGCGUGUGUGGGG	17	6640
  BCL11A-5010	-	AGUCGAGGUAAAAGAGAUAA	20	6641
  BCL11A-5011	+	AGUGCGGGGAGGGGGAGGUG	20	6642
  BCL11A-5012	+	AUAAUACAAAGAUGGCG	17	6643
  BCL11A-5013	-	AUAAUCACGAGAGCGCG	17	6644
  BCL11A-5014	+	AUACACGGCAAUGGUUCCAG	20	6645
  BCL11A-5015	+	AUAGAGGGAGAGAGAGA	17	6646
  BCL11A-5016	+	AUCAGGGGCUGGACAUGAAA	20	6647
  BCL11A-5017	+	AUCGGGAGAGCCGGGUUAGA	20	6648
  BCL11A-5018	+	AUCUCUUUUACCUCGACUCU	20	6649
  BCL11A-5019	+	AUGGCCAGUGCGGGGAG	17	6650
  BCL11A-5020	+	AUGGGCAGGGCGAGCAG	17	6651
  BCL11A-5021	+	AUGGUUCCAGAUGGGAU	17	6652
  BCL11A-5022	+	AUUAUUGGGUUACUUAC	17	6653
  BCL11A-5023	-	AUUAUUUCUAAUUUAUU	17	6654
  BCL11A-5024	+	AUUCCCGUUUGCUUAAGUGC	20	6655
  BCL11A-5025	-	AUUUUAGAGUCCGCGUGUGU	20	6656
  BCL11A-5026	-	AUUUUUAAAUUUUUCAC	17	6657
  BCL11A-5027	-	AUUUUUCACGAGAAAAACCU	20	6658
  BCL11A-5028	+	CAAAACAUGGGCAGGGCGAG	20	6659
  BCL11A-5029	-	CAAAAGCGAGGGGGAGA	17	6660
  BCL11A-5030	+	CAAGCCAAUGGCCAGUG	17	6661
  BCL11A-5031	+	CAAUGGACACACAUCAGGGG	20	6662
  BCL11A-5032	+	CAAUGGCCAGUGCGGGG	17	6663
  BCL11A-5033	+	CAAUGGCCAGUGCGGGGAGG	20	6664
  BCL11A-5034	+	CAAUGGUUCCAGAUGGG	17	6665
  BCL11A-5035	+	CACAAAACAUGGGCAGG	17	6666
  BCL11A-5036	+	CACACCAAUGGACACACAUC	20	6667
  BCL11A-5037	+	CACACGCGGACUCUAAA	17	6668
  BCL11A-5038	+	CACAUCAGGGGCUGGAC	17	6669
  BCL11A-5039	+	CACCAAUGGACACACAU	17	6670
  BCL11A-5040	+	CACGGCAAUGGUUCCAG	17	6671
  BCL11A-5041	-	CACUGAUGAAGAUAUUUUCU	20	6672
  BCL11A-5042	-	CACUUGAACUUGCAGCU	17	6673
  BCL11A-5043	-	CACUUGAACUUGCAGCUCAG	20	6674
  BCL11A-5044	-	CAGGACUAGAAGCAAAA	17	6675
  BCL11A-5045	-	CAGGACUAGAAGCAAAAGCG	20	6676
  BCL11A-5046	+	CAGGAGAGAAGGGGAGG	17	6677
  BCL11A-5047	+	CAGGGAAGAUGAAUUGU	17	6678
  BCL11A-5048	+	CAGGGCGAGCAGGAGAG	17	6679
  BCL11A-5049	+	CAGGGCGAGCAGGAGAGAAG	20	6680
  BCL11A-5050	+	CAGGGGUGGGAGGAAAGGGU	20	6681
  BCL11A-5051	+	CAGUGCGGGGAGGGGGAGGU	20	6682
  BCL11A-5052	-	CAUGCAUUUUUAAAUUUUUC	20	6683
  BCL11A-5053	+	CAUGGGCAGGGCGAGCAGGA	20	6684
  BCL11A-5054	-	CAUUUUAGAGUCCGCGUGUG	20	6685
  BCL11A-5055	+	CCAAUGGCCAGUGCGGG	17	6686
  BCL11A-5056	+	CCAAUGGCCAGUGCGGGGAG	20	6687
  BCL11A-5057	+	CCACACACGCGGACUCUAAA	20	6688
  BCL11A-5058	+	CCAGACGCGGCCCCCGG	17	6689
  BCL11A-5059	+	CCAGACGCGGCCCCCGGGGG	20	6690
  BCL11A-5060	-	CCAGCACUUAAGCAAAC	17	6691
  BCL11A-5061	-	CCAUUGCCGUGUAUGCACUU	20	6692
  BCL11A-5062	-	CCCAGCACUUAAGCAAA	17	6693
  BCL11A-5063	-	CCCCAGCACUUAAGCAA	17	6694
  BCL11A-5064	+	CCCCGGGGGAGGGGCGGGCC	20	6695
  BCL11A-5065	-	CCCCUCGGCCCGCCCCUCCC	20	6696
  BCL11A-5066	+	CCCGGGGGAGGGGCGGG	17	6697
  BCL11A-5067	+	CCCGGGGGAGGGGCGGGCCG	20	6698
  BCL11A-5068	+	CCCGUUUGCUUAAGUGC	17	6699
  BCL11A-5069	-	CCCUCGGCCCGCCCCUCCCC	20	6700
  BCL11A-5070	+	CCCUGCUCCCCCCCACACAC	20	6701
  BCL11A-5071	+	CCGAGGGGAGGGGGCGC	17	6702
  BCL11A-5072	-	CCGCACUUGAACUUGCAGCU	20	6703
  BCL11A-5073	+	CCGCGGCGGUGGCGUGG	17	6704
  BCL11A-5074	+	CCGGGGGAGGGGCGGGCCGA	20	6705
  BCL11A-5075	-	CCUCGGCCCGCCCCUCCCCC	20	6706
  BCL11A-5076	-	CCUGACGUUCAAGUUCG	17	6707
  BCL11A-5077	+	CCUGAGCUGCAAGUUCAAGU	20	6708
  BCL11A-5078	-	CCUGAUGUGUGUCCAUUGGU	20	6709
  BCL11A-5079	+	CGAACUUGAACGUCAGGAGU	20	6710
  BCL11A-5080	+	CGAGACAUGGUGGGCUG	17	6711
  BCL11A-5081	+	CGAGCAGGAGAGAAGGG	17	6712
  BCL11A-5082	+	CGAGCAGGAGAGAAGGGGAG	20	6713
  BCL11A-5083	-	CGAGGUAAAAGAGAUAA	17	6714
  BCL11A-5084	-	CGAGGUAAAAGAGAUAAAGG	20	6715
  BCL11A-5085	-	CGCACUUGAACUUGCAGCUC	20	6716
  BCL11A-5086	+	CGCAGGGAAGAUGAAUU	17	6717
  BCL11A-5087	+	CGCCAGACGCGGCCCCC	17	6718
  BCL11A-5088	+	CGCCGCGGCGGUGGCGUGGC	20	6719
  BCL11A-5089	+	CGCGGCGGUGGCGUGGC	17	6720
  BCL11A-5090	+	CGCGGCGGUGGCGUGGCCGG	20	6721
  BCL11A-5091	+	CGGACGCCAGACGCGGCCCC	20	6722
  BCL11A-5092	+	CGGCAAUGGUUCCAGAUGGG	20	6723
  BCL11A-5093	+	CGGCCCCCGGGGGAGGG	17	6724
  BCL11A-5094	-	CGGCCCGCCCCUCCCCC	17	6725
  BCL11A-5095	+	CGGCGAGACAUGGUGGGCUG	20	6726
  BCL11A-5096	+	CGGCGGCGGCGGCGGCG	17	6727
  BCL11A-5097	+	CGGCGGCGGCGGCGGCGGCG	20	6728
  BCL11A-5098	+	CGGCGGUGGCGUGGCCGGGA	20	6729
  BCL11A-5099	+	CGGGCCGAGGGGAGGGGGCG	20	6730
  BCL11A-5100	+	CGGGCUCACCAGUGGCCGCA	20	6731
  BCL11A-5101	+	CGGGGAGGGGGAGGUGCGGG	20	6732
  BCL11A-5102	+	CGGGGGAGGGGCGGGCC	17	6733
  BCL11A-5103	+	CGGGGGAGGGGCGGGCCGAG	20	6734
  BCL11A-5104	+	CGGUGGCGUGGCCGGGA	17	6735
  BCL11A-5105	+	CGGUGGCGUGGCCGGGAGAG	20	6736
  BCL11A-5106	-	CUAGAAGCAAAAGCGAG	17	6737
  BCL11A-5107	-	CUAGAAGCAAAAGCGAGGGG	20	6738
  BCL11A-5108	-	CUCCUGACGUUCAAGUUCGC	20	6739
  BCL11A-5109	-	CUCGGCCCGCCCCUCCC	17	6740
  BCL11A-5110	+	CUCUUUUACCUCGACUC	17	6741
  BCL11A-5111	-	CUGACGUUCAAGUUCGC	17	6742
  BCL11A-5112	+	CUUGAACGUCAGGAGUCUGG	20	6743
  BCL11A-5113	-	CUUGAACUUGCAGCUCA	17	6744
  BCL11A-5114	+	CUUGCUUGCGGCGAGACAUG	20	6745
  BCL11A-5115	-	UAAUAAUUAUUAAUAAUCAC	20	6746
  BCL11A-5116	+	UAAUACAAAGAUGGCGC	17	6747
  BCL11A-5117	-	UAAUUAUUAAUAAUCAC	17	6748
  BCL11A-5118	+	UACACGGCAAUGGUUCCAGA	20	6749
  BCL11A-5119	+	UAGAAAGAAGGAGACUC	17	6750
  BCL11A-5120	-	UAGAAGCAAAAGCGAGG	17	6751
  BCL11A-5121	-	UAGAGUCCGCGUGUGUG	17	6752
  BCL11A-5122	-	UAGAGUCCGCGUGUGUGGGG	20	6753
  BCL11A-5123	+	UAUCUCUUUUACCUCGACUC	20	6754
  BCL11A-5124	+	UAUUAUUGGGUUACUUACGC	20	6755
  BCL11A-5125	+	UAUUGGGUUACUUACGC	17	6756
  BCL11A-5126	+	UCACACCAAUGGACACACAU	20	6757
  BCL11A-5127	-	UCACGAGAAAAACCUCC	17	6758
  BCL11A-5128	+	UCAGGAGUCUGGAUGGA	17	6759
  BCL11A-5129	-	UCAUUUUAGAGUCCGCGUGU	20	6760
  BCL11A-5130	+	UCCCGUUUGCUUAAGUG	17	6761
  BCL11A-5131	-	UCCGAGAGUCGAGGUAA	17	6762
  BCL11A-5132	-	UCCGCGUGUGUGGGGGGGAG	20	6763
  BCL11A-5133	-	UCGAGGUAAAAGAGAUA	17	6764
  BCL11A-5134	-	UCGAGGUAAAAGAGAUAAAG	20	6765
  BCL11A-5135	-	UCGGCCCGCCCCUCCCC	17	6766
  BCL11A-5136	-	UCUAACCCGGCUCUCCCGAU	20	6767
  BCL11A-5137	+	UCUCGGAGGUUUUUCUC	17	6768
  BCL11A-5138	+	UCUUUUACCUCGACUCU	17	6769
  BCL11A-5139	+	UGACAUCCAAAAUAAAU	17	6770
  BCL11A-5140	-	UGAUGAAGAUAUUUUCU	17	6771
  BCL11A-5141	-	UGCAUUUUUAAAUUUUUCAC	20	6772
  BCL11A-5142	+	UGCGGGGAGGGGGAGGU	17	6773
  BCL11A-5143	+	UGCUCCCCCCCACACAC	17	6774
  BCL11A-5144	+	UGGACACACAUCAGGGG	17	6775
  BCL11A-5145	+	UGGACAGAGACACACAAAAC	20	6776
  BCL11A-5146	+	UGGCAGGGGUGGGAGGA	17	6777
  BCL11A-5147	+	UGGCCAGUGCGGGGAGG	17	6778
  BCL11A-5148	+	UGGCCGGGAGAGAAGAA	17	6779
  BCL11A-5149	+	UGGCGCAGGGAAGAUGAAUU	20	6780
  BCL11A-5150	+	UGGCGUGGCCGGGAGAG	17	6781
  BCL11A-5151	+	UGGGAGGAAAGGGUGGG	17	6782
  BCL11A-5152	+	UGGGGUUUGCCUUGCUUGCG	20	6783
  BCL11A-5153	-	UGUAUUAUUUCUAAUUUAUU	20	6784
  BCL11A-5154	-	UUAAUAAUCACGAGAGCGCG	20	6785
  BCL11A-5155	+	UUAGAAAGAAGGAGACUCCA	20	6786
  BCL11A-5156	-	UUAGAGUCCGCGUGUGU	17	6787
  BCL11A-5157	-	UUAGAGUCCGCGUGUGUGGG	20	6788
  BCL11A-5158	-	UUGAACUUGCAGCUCAG	17	6789
  BCL11A-5159	-	UUGCCGUGUAUGCACUU	17	6790
  BCL11A-5160	-	UUGGAUGUCAAAAGGCACUG	20	6791
  BCL11A-5161	-	UUUAGAGUCCGCGUGUG	17	6792
  BCL11A-5162	-	UUUAGAGUCCGCGUGUGUGG	20	6793
  BCL11A-5163	-	UUUCACGAGAAAAACCU	17	6794
  BCL11A-5164	-	UUUUAGAGUCCGCGUGU	17	6795
  BCL11A-5165	-	UUUUAGAGUCCGCGUGUGUG	20	6796
  BCL11A-5166	-	UUUUCACGAGAAAAACCUCC	20	6797
  BCL11A-5167	+	UUUUGACAUCCAAAAUAAAU	20	6798

• Table 12 provides exemplary targeting domains for knocking down expression of the BCL11A gene. The targeting domains bind between 500 bp upstream and 500 bp 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. meningitidismeningitidis eiCas9 molecule to cause a steric block at the target region, e.g., between 500 bp upstream and 500 bp 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. meningitidismeningitidis eiCas9 fused to a transcriptional repressor to decrease transcription and therefore downregulate gene expression.

• TABLE 12
  	DNA		Target Site	SEQ ID
  gRNA Name	Strand	Targeting Domain	Length	NO
  BCL11A-5168	+	GCUUCUAGUCCUGCGCGCUC	20	6799
  BCL11A-5169	+	ACACACGCGGACUCUAAAAU	20	6800
  BCL11A-5170	+	UCUAGUCCUGCGCGCUC	17	6801
  BCL11A-5171	+	CACGCGGACUCUAAAAU	17	6802

• Table 13A provides exemplary targeting domains for the E6V target site in the HBB gene selected according to the first tier parameters. The targeting domains bind within 100 bp upstream and 100 bp downstream of the target position, good orthogonality 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).
• 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 0-50 bp. Exemplary gRNA pairs are: HBB-9 and HBB-11, HBB-9 and HBB-39, HBB-20 and HBB-11 and HBB-20 and HBB-39.

• TABLE 13A
  1st Tier

  	DNA		Target Site	SEQ ID
  gRNA Name	Strand	Targeting Domain	Length	NO
  HBB-1	-	GGUGCACCUGACUCCUG	17	6803
  HBB-2	+	GUAACGGCAGACUUCUCCAC	20	6804

• Table 13B provides exemplary targeting domains for the E6V target site in the HBB gene selected according to the second tier parameters. The targeting domains bind within 100 bp upstream and 100 bp downstream of the target position, 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).
• 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 0-50 bp.

• TABLE 13B
  2nd Tier

  	DNA		Target Site	SEQ ID
  gRNA Name	Strand	Targeting Domain	Length	NO
  HBB-3	+	ACGGCAGACUUCUCCAC	17	6805
  HBB-4	+	ACUUCUCCACAGGAGUC	17	6806
  HBB-5	+	AGGAGUCAGGUGCACCA	17	6807
  HBB-6	-	CAUGGUGCACCUGACUCCUG	20	6808
  HBB-7	+	CACAGGAGUCAGGUGCACCA	20	6809
  HBB-8	+	CAGACUUCUCCACAGGAGUC	20	6810

• Table 13C provides exemplary targeting domains for the E6V target site in the HBB gene selected according to the third tier parameters. The targeting domains bind within 100 bp upstream and 100 bp downstream of the target position, 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).
• 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 0-50 bp.

• TABLE 13C
  3rd Tier

  	DNA		Target Site	SEQ ID
  gRNA Name	Strand	Targeting Domain	Length	NO
  HBB-9	-	GAAGUUGGUGGUGAGGCCCU	20	6811
  HBB-10	-	GCAACCUCAAACAGACACCA	20	6812
  HBB-11	+	GCCCCACAGGGCAGUAA	17	6813
  HBB-12	-	GCCGUUACUGCCCUGUG	17	6814
  HBB-13	-	GGAUGAAGUUGGUGGUG	17	6815
  HBB-14	-	GUCUGCCGUUACUGCCCUGU	20	6816
  HBB-15	-	GUGAACGUGGAUGAAGU	17	6817
  HBB-16	-	GUGAACGUGGAUGAAGUUGG	20	6818
  HBB-17	-	GUGGGGCAAGGUGAACG	17	6819
  HBB-18	-	GUGGUGAGGCCCUGGGC	17	6820
  HBB-19	+	GUUCACCUUGCCCCACA	17	6821
  HBB-20	-	GUUGGUGGUGAGGCCCU	17	6822

• Table 13D provides exemplary targeting domains for the E6V target site in the HBB gene selected according to the fourth tier parameters. The targeting domains bind within 100 bp upstream and 100 bp downstream of the target position, 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).
• 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 0-50 bp.

• TABLE 13D
  4th Tier

  	DNA		Target Site	SEQ ID
  gRNA Name	Strand	Targeting Domain	Length	NO
  HBB-21	-	AACGUGGAUGAAGUUGG	17	6823
  HBB-22	+	AAGCAAAUGUAAGCAAUAGA	20	6824
  HBB-23	-	AAGGUGAACGUGGAUGAAGU	20	6825
  HBB-24	+	ACCAUGGUGUCUGUUUG	17	6826
  HBB-25	-	ACCUCAAACAGACACCA	17	6827
  HBB-26	+	ACCUUGAUACCAACCUGCCC	20	6828
  HBB-27	-	AGUCUGCCGUUACUGCCCUG	20	6829
  HBB-28	-	AGUUGGUGGUGAGGCCC	17	6830
  HBB-29	+	CAAAUGUAAGCAAUAGA	17	6831
  HBB-30	+	CACGUUCACCUUGCCCCACA	20	6832
  HBB-31	+	CCACGUUCACCUUGCCCCAC	20	6833
  HBB-32	-	CCCUGGGCAGGUUGGUAUCA	20	6834
  HBB-33	-	CCUGUGGGGCAAGGUGAACG	20	6835
  HBB-34	+	CCUUGAUACCAACCUGCCCA	20	6836
  HBB-35	-	CGUGGAUGAAGUUGGUGGUG	20	6837
  HBB-36	-	CGUUACUGCCCUGUGGGGCA	20	6838
  HBB-37	+	CGUUCACCUUGCCCCAC	17	6839
  HBB-38	-	CUGCCGUUACUGCCCUG	17	6840
  HBB-39	+	CUUGCCCCACAGGGCAGUAA	20	6841
  HBB-40	-	UACUGCCCUGUGGGGCA	17	6842
  HBB-41	-	UAUCAAGGUUACAAGAC	17	6843
  HBB-42	-	UCUGCCGUUACUGCCCUGUG	20	6844
  HBB-43	-	UGAAGUUGGUGGUGAGGCCC	20	6845
  HBB-44	-	UGAGGCCCUGGGCAGGU	17	6846
  HBB-45	+	UGAUACCAACCUGCCCA	17	6847
  HBB-46	+	UGCACCAUGGUGUCUGUUUG	20	6848
  HBB-47	-	UGCCGUUACUGCCCUGU	17	6849
  HBB-48	-	UGGGCAGGUUGGUAUCA	17	6850
  HBB-49	-	UGGUAUCAAGGUUACAAGAC	20	6851
  HBB-50	-	UGGUGAGGCCCUGGGCAGGU	20	6852
  HBB-51	+	UUGAUACCAACCUGCCC	17	6853
  HBB-52	-	UUGGUGGUGAGGCCCUGGGC	20	6854

• Table 14A provides exemplary targeting domains for the E6V target site in the HBB gene selected according to the first tier parameters. The targeting domains bind within 100 bp upstream and 100 bp downstream of the target position, good orthogonality 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).
• 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 0-50 bp. Exemplary gRNA pairs are: HBB-9 and HBB-11, HBB-9 and HBB-39, HBB-20 and HBB-11 and HBB-20 and HBB-39.

• TABLE 14A
  1st Tier

  	DNA		Target Site	SEQ ID
  gRNA Name	Strand	Targeting Domain	Length	NO
  HBB-53	+	GUAACGGCAGACUUCUCCAC	20	6855

• Table 14B provides exemplary targeting domains for the E6V target site in the HBB gene selected according to the second tier parameters. The targeting domains bind within 100 bp upstream and 100 bp downstream of the target position, 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).
• 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 0-50 bp.

• TABLE 14B
  2nd Tier

  	DNA		Target Site	SEQ ID
  gRNA Name	Strand	Targeting Domain	Length	NO
  HBB-54	-	CCCUGUGGGGCAAGGUGGAC	20	6856

• Table 14C provides exemplary targeting domains for the E6V target site in the HBB gene selected according to the fifth tier parameters. The targeting domains bind within 100 bp upstream and 100 bp downstream of the target position and PAM is NNGRRV. 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 0-50 bp.

• TABLE 14C
  5th Tier

  	DNA		Target Site	SEQ ID
  gRNA Name	Strand	Targeting Domain	Length	NO
  HBB-55	-	AGUCUGCCGUUACUGCCCUG	20	6857
  HBB-56	-	AAGUCUGCCGUUACUGCCCU	20	6858
  HBB-57	+	AACCUUGAUACCAACCUGCC		20	6859
  HBB-58	+	UCCACGUUCACCUUGCCCCA		20	6860
  HBB-59	+	GCUAGUGAACACAGUUGUGU		20	6861
  HBB-60	-	CCAUGGUGCACCUGACUCCU	20	6862
  HBB-61	-	CAUGGUGCACCUGACUCCUG	20	6863
  HBB-62	+	AGGUGCACCAUGGUGUCUGU		20	6864
  HBB-63	-	UGGUGCACCUGACUCCUGUG	20	6865
  HBB-64	-	GAACGUGGAUGAAGUUGGUG	20	6866
  HBB-65	-	UUACUGCCCUGUGGGGCAAG	20	6867
  HBB-66	+	GUGUCUGUUUGAGGUUGCUA		20	6868
  HBB-67	-	GUGGGGCAAGGUGAACGUGG	20	6869
  HBB-68	-	AUGAAGUUGGUGGUGAGGCC	20	6870
  HBB-69	+	AGUAACGGCAGACUUCUCCA		20	6871

• Table 15A 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 15A
  1st Tier

  	DNA		Target Site	SEQ ID
  gRNA Name	Strand	Targeting Domain	Length	NO:
  BCL11A-5318	+	UCAUCUCGAUUGGUGAA	17	6872
  BCL11A-5319	+	UUGCUUGCGGCGAGACA	17	6873
  BCL11A-5320	-	AUGUCUCGCCGCAAGCA	17	6874
  BCL11A-5321	-	GCAGAAUAUGCCCCGCA	17	6875
  BCL11A-5322	-	CCGUUGGGAGCUCCAGA	17	6876
  BCL11A-5323	+	CUCCAUGUGCAGAACGA	17	6877
  BCL11A-5324	+	UCGAUUGGUGAAGGGGA	17	6878
  BCL11A-5325	+	CAUCCUCUGGCGUGACC	17	6879
  BCL11A-5326	-	GCUCUAAUCCCCACGCC	17	6880
  BCL11A-5327	+	CCCGUUUGCUUAAGUGC	17	6881
  BCL11A-5328	+	AAACAAUCGUCAUCCUC	17	6882
  BCL11A-5329	+	CCCAACGGGCCGUGGUC	17	6883
  BCL11A-5330	+	CAUCUCGAUUGGUGAAG	17	6884
  BCL11A-5331	-	CAUCCAGGUCACGCCAG	17	6885
  BCL11A-5332	-	UUAUCAACGUCAUCUAG	17	6886
  BCL11A-5333	+	GAGCUCCCAACGGGCCG	17	6887
  BCL11A-5334	+	UGCACUCAUCCCAGGCG	17	6888
  BCL11A-5335	+	AGACAUGGUGGGCUGCG	17	6889
  BCL11A-5336	+	CGUUUGCUUAAGUGCUG	17	6890
  BCL11A-5337	+	GCUUUUUUCAUCUCGAU	17	6891
  BCL11A-5338	+	CCGUUUGCUUAAGUGCU	17	6892
  BCL11A-5339	-	UCCAAUCCCGUGGAGGU	17	6893
  BCL11A-5340	+	UUGCGGCGAGACAUGGU	17	6894
  BCL11A-5341	-	AUGACCUCCUCACCUGU	17	6895
  BCL11A-5342	-	UUAUUUUUAUCGAGCACAAA	20	6896
  BCL11A-5343	+	UCCCCUUCUGGAGCUCCCAA	20	6897
  BCL11A-5344	+	UUUUCAUCUCGAUUGGUGAA	20	6898
  BCL11A-5345	+	GCCUUGCUUGCGGCGAGACA	20	6899
  BCL11A-5346	-	ACCAUGUCUCGCCGCAAGCA	20	6900
  BCL11A-5347	+	GAGCUCCAUGUGCAGAACGA	20	6901
  BCL11A-5348	-	UCACAGAUAAACUUCUGCAC	20	6902
  BCL11A-5349	+	CGUCAUCCUCUGGCGUGACC	20	6903
  BCL11A-5350	-	GGAGCUCUAAUCCCCACGCC	20	6904
  BCL11A-5351	-	UCCCGUGGAGGUUGGCAUCC	20	6905
  BCL11A-5352	+	AUUCCCGUUUGCUUAAGUGC	20	6906
  BCL11A-5353	+	CCCCCAAUGGGAAGUUCAUC	20	6907
  BCL11A-5354	+	GCUCCCAACGGGCCGUGGUC	20	6908
  BCL11A-5355	+	UUUCAUCUCGAUUGGUGAAG	20	6909
  BCL11A-5356	-	UGUUUAUCAACGUCAUCUAG	20	6910
  BCL11A-5357	+	AGAGCUCCAUGUGCAGAACG	20	6911
  BCL11A-5358	-	GAAAAAAGCAUCCAAUCCCG	20	6912
  BCL11A-5359	+	GCGAGACAUGGUGGGCUGCG	20	6913
  BCL11A-5360	-	CAGAUAAACUUCUGCACUGG	20	6914
  BCL11A-5361	+	CGGCGAGACAUGGUGGGCUG	20	6915
  BCL11A-5362	+	CUGCACUCAUCCCAGGCGUG	20	6916
  BCL11A-5363	-	UGAACCAGACCACGGCCCGU	20	6917
  BCL11A-5364	-	GCAUCCAAUCCCGUGGAGGU	20	6918
  BCL11A-5365	+	UGCUUGCGGCGAGACAUGGU	20	6919
  BCL11A-5366	+	UCAAGAGGCUCGGCUGUGGU	20	6920
  BCL11A-5367	-	AUCAUGACCUCCUCACCUGU	20	6921

• Table 15B 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 15B
  2nd Tier

  	DNA		Target Site	SEQ ID
  gRNA Name	Strand	Targeting Domain	Length	NO:
  BCL11A-5368	-	UUUUUAUCGAGCACAAA	17	6922
  BCL11A-5369	-	CCCAGCACUUAAGCAAA	17	6923
  BCL11A-5370	+	AUAAGAAUGUCCCCCAA	17	6924
  BCL11A-5371	+	CCUUCUGGAGCUCCCAA	17	6925
  BCL11A-5372	-	AAACGGAAACAAUGCAA	17	6926
  BCL11A-5373	+	UUCAUCAUCUGUAAGAA	17	6927
  BCL11A-5374	-	CGUUGGGAGCUCCAGAA	17	6928
  BCL11A-5375	-	UCCCCUCGUUCUGCACA	17	6929
  BCL11A-5376	-	GAUGAUGAACCAGACCA	17	6930
  BCL11A-5377	+	CUGGAUGCCAACCUCCA	17	6931
  BCL11A-5378	-	CAGGUAAAUGAGAAGCA	17	6932
  BCL11A-5379	-	UAAACUUCUGCACUGGA	17	6933
  BCL11A-5380	+	UUCAUCUCGAUUGGUGA	17	6934
  BCL11A-5381	+	CAUUUGUAGAAGAAAUA	17	6935
  BCL11A-5382	-	AGGAAUUUGCCCCAAAC	17	6936
  BCL11A-5383	-	CCAGCACUUAAGCAAAC	17	6937
  BCL11A-5384	+	CUUCUGGAGCUCCCAAC	17	6938
  BCL11A-5385	+	CAUCUGGCACUGCCCAC	17	6939
  BCL11A-5386	+	UGGAUGCCAACCUCCAC	17	6940
  BCL11A-5387	-	CAGAUAAACUUCUGCAC	17	6941
  BCL11A-5388	+	UAUUCUGCACUCAUCCC	17	6942
  BCL11A-5389	-	CGUGGAGGUUGGCAUCC	17	6943
  BCL11A-5390	-	AAACAGGAACACAUAGC	17	6944
  BCL11A-5391	-	UGCAGAAUAUGCCCCGC	17	6945
  BCL11A-5392	+	AUGGUGGGCUGCGGGGC	17	6946
  BCL11A-5393	+	ACUUACAAAUACCCUGC	17	6947
  BCL11A-5394	+	UGUACAUGUGUAGCUGC	17	6948
  BCL11A-5395	+	GAGACAUGGUGGGCUGC	17	6949
  BCL11A-5396	-	GUGUUGUAUUAUUUUGC	17	6950
  BCL11A-5397	+	CCAAUGGGAAGUUCAUC	17	6951
  BCL11A-5398	+	AGGUCAUGAUCCCCUUC	17	6952
  BCL11A-5399	+	GUAAGAAUGGCUUCAAG	17	6953
  BCL11A-5400	-	GUUGGGAGCUCCAGAAG	17	6954
  BCL11A-5401	+	CAGCUUUUUCUAAGCAG	17	6955
  BCL11A-5402	+	UCCAUGUGCAGAACGAG	17	6956
  BCL11A-2671	+	CAGAACGAGGGGAGGAG	17	6957
  BCL11A-5403	-	AAACUUCUGCACUGGAG	17	6958
  BCL11A-5404	+	GCUCCAUGUGCAGAACG	17	6959
  BCL11A-5405	-	AAAAGCAUCCAAUCCCG	17	6960
  BCL11A-5406	+	CUUACAAAUACCCUGCG	17	6961
  BCL11A-5407	+	AUUGGUGAAGGGGAAGG	17	6962
  BCL11A-5408	+	ACUGCCCACAGGUGAGG	17	6963
  BCL11A-4500	+	GGGGCGGGCGGCGGCGG	17	6964
  BCL11A-5409	+	UGCGGGGCGGGCGGCGG	17	6965
  BCL11A-5410	+	GGCUGCGGGGCGGGCGG	17	6966
  BCL11A-5411	+	GUGGGCUGCGGGGCGGG	17	6967
  BCL11A-5412	+	AUGUGCAGAACGAGGGG	17	6968
  BCL11A-5413	+	CAUGGUGGGCUGCGGGG	17	6969
  BCL11A-5414	+	CUUGCGGCGAGACAUGG	17	6970
  BCL11A-5415	-	AUAAACUUCUGCACUGG	17	6971
  BCL11A-5416	-	AGCAUCCAAUCCCGUGG	17	6972
  BCL11A-5417	-	GAUGAACUUCCCAUUGG	17	6973
  BCL11A-5418	-	CAUGACCUCCUCACCUG	17	6974
  BCL11A-5419	+	AACUUACAAAUACCCUG	17	6975
  BCL11A-5420	-	CUGCUUAGAAAAAGCUG	17	6976
  BCL11A-5421	+	UUCAAGAGGCUCGGCUG	17	6977
  BCL11A-5422	+	CGAGACAUGGUGGGCUG	17	6978
  BCL11A-5423	+	CACUCAUCCCAGGCGUG	17	6979
  BCL11A-5424	+	GGCACUGCCCACAGGUG	17	6980
  BCL11A-5425	-	AGAUGAACUUCCCAUUG	17	6981
  BCL11A-5426	+	GGGGUUUGCCUUGCUUG	17	6982
  BCL11A-5427	+	CUAUGUGUUCCUGUUUG	17	6983
  BCL11A-5428	+	UAAGAAUGUCCCCCAAU	17	6984
  BCL11A-5429	-	CCAGAUGAACUUCCCAU	17	6985
  BCL11A-5430	+	GCCAACCUCCACGGGAU	17	6986
  BCL11A-5431	+	AUUAUUAUUACUAUUAU	17	6987
  BCL11A-5432	-	CUCUAAUCCCCACGCCU	17	6988
  BCL11A-5433	+	AAUGGCUUCAAGAGGCU	17	6989
  BCL11A-5434	+	GUACAUGUGUAGCUGCU	17	6990
  BCL11A-5435	-	ACCAGACCACGGCCCGU	17	6991
  BCL11A-5436	+	GCACUCAUCCCAGGCGU	17	6992
  BCL11A-5437	+	AGAGGCUCGGCUGUGGU	17	6993
  BCL11A-5438	-	CAGAUGAACUUCCCAUU	17	6994
  BCL11A-5439	+	UUAUUAUUACUAUUAUU	17	6995
  BCL11A-5440	-	CCAGACCACGGCCCGUU	17	6996
  BCL11A-5441	+	UGCUAUGUGUUCCUGUU	17	6997
  BCL11A-5442	+	GCUAUGUGUUCCUGUUU	17	6998
  BCL11A-5443	-	AACCCCAGCACUUAAGCAAA	20	6999
  BCL11A-5444	+	AAAAUAAGAAUGUCCCCCAA	20	7000
  BCL11A-5445	-	CACAAACGGAAACAAUGCAA	20	7001
  BCL11A-5446	+	UGGUUCAUCAUCUGUAAGAA	20	7002
  BCL11A-5447	-	GCCCGUUGGGAGCUCCAGAA	20	7003
  BCL11A-5448	-	UCCUCCCCUCGUUCUGCACA	20	7004
  BCL11A-5449	-	ACAGAUGAUGAACCAGACCA	20	7005
  BCL11A-5450	+	GACCUGGAUGCCAACCUCCA	20	7006
  BCL11A-5451	-	UAGCAGGUAAAUGAGAAGCA	20	7007
  BCL11A-5452	-	AGUGCAGAAUAUGCCCCGCA	20	7008
  BCL11A-5453	-	GGCCCGUUGGGAGCUCCAGA	20	7009
  BCL11A-5454	+	AUCUCGAUUGGUGAAGGGGA	20	7010
  BCL11A-5455	-	AGAUAAACUUCUGCACUGGA	20	7011
  BCL11A-5456	+	UUUUUCAUCUCGAUUGGUGA	20	7012
  BCL11A-5457	-	UAGAGGAAUUUGCCCCAAAC	20	7013
  BCL11A-5458	-	ACCCCAGCACUUAAGCAAAC	20	7014
  BCL11A-5459	+	CCCCUUCUGGAGCUCCCAAC	20	7015
  BCL11A-5460	+	GUUCAUCUGGCACUGCCCAC	20	7016
  BCL11A-5461	+	ACCUGGAUGCCAACCUCCAC	20	7017
  BCL11A-5462	+	GCAUAUUCUGCACUCAUCCC	20	7018
  BCL11A-5463	-	CCCAAACAGGAACACAUAGC	20	7019
  BCL11A-5464	-	GAGUGCAGAAUAUGCCCCGC	20	7020
  BCL11A-5465	+	GACAUGGUGGGCUGCGGGGC	20	7021
  BCL11A-5466	+	UCAACUUACAAAUACCCUGC	20	7022
  BCL11A-5467	+	AGUUGUACAUGUGUAGCUGC	20	7023
  BCL11A-5468	+	GGCGAGACAUGGUGGGCUGC	20	7024
  BCL11A-5469	-	UUGGUGUUGUAUUAUUUUGC	20	7025
  BCL11A-5470	+	GAUAAACAAUCGUCAUCCUC	20	7026
  BCL11A-5471	+	AGGAGGUCAUGAUCCCCUUC	20	7027
  BCL11A-5472	+	UCUGUAAGAAUGGCUUCAAG	20	7028
  BCL11A-5473	-	CCCGUUGGGAGCUCCAGAAG	20	7029
  BCL11A-5474	-	UGGCAUCCAGGUCACGCCAG	20	7030
  BCL11A-5475	+	CCACAGCUUUUUCUAAGCAG	20	7031
  BCL11A-5476	+	AGCUCCAUGUGCAGAACGAG	20	7032
  BCL11A-5477	+	GUGCAGAACGAGGGGAGGAG	20	7033
  BCL11A-5478	-	GAUAAACUUCUGCACUGGAG	20	7034
  BCL11A-5479	+	CUGGAGCUCCCAACGGGCCG	20	7035
  BCL11A-5480	+	UUCUGCACUCAUCCCAGGCG	20	7036
  BCL11A-5481	+	CAACUUACAAAUACCCUGCG	20	7037
  BCL11A-5482	+	UCGAUUGGUGAAGGGGAAGG	20	7038
  BCL11A-5483	+	GGCACUGCCCACAGGUGAGG	20	7039
  BCL11A-5484	+	UGCGGGGCGGGCGGCGGCGG	20	7040
  BCL11A-5485	+	GGCUGCGGGGCGGGCGGCGG	20	7041
  BCL11A-5486	+	GUGGGCUGCGGGGCGGGCGG	20	7042
  BCL11A-5487	+	AUGGUGGGCUGCGGGGCGGG	20	7043
  BCL11A-5488	+	UCCAUGUGCAGAACGAGGGG	20	7044
  BCL11A-5489	+	AGACAUGGUGGGCUGCGGGG	20	7045
  BCL11A-5490	+	UUGCUUGCGGCGAGACAUGG	20	7046
  BCL11A-5491	-	AAAAGCAUCCAAUCCCGUGG	20	7047
  BCL11A-5492	-	CCAGAUGAACUUCCCAUUGG	20	7048
  BCL11A-5493	-	GAUCAUGACCUCCUCACCUG	20	7049
  BCL11A-5494	+	CUCAACUUACAAAUACCCUG	20	7050
  BCL11A-5495	-	CCUCUGCUUAGAAAAAGCUG	20	7051
  BCL11A-5496	+	GGCUUCAAGAGGCUCGGCUG	20	7052
  BCL11A-5497	+	UCCCGUUUGCUUAAGUGCUG	20	7053
  BCL11A-5498	+	UCUGGCACUGCCCACAGGUG	20	7054
  BCL11A-5499	-	GCCAGAUGAACUUCCCAUUG	20	7055
  BCL11A-5500	+	GCUGGGGUUUGCCUUGCUUG	20	7056
  BCL11A-5501	+	CUGCUAUGUGUUCCUGUUUG	20	7057
  BCL11A-5502	+	AAAUAAGAAUGUCCCCCAAU	20	7058
  BCL11A-5503	-	GUGCCAGAUGAACUUCCCAU	20	7059
  BCL11A-5504	+	GAUGCUUUUUUCAUCUCGAU	20	7060
  BCL11A-5505	+	GAUGCCAACCUCCACGGGAU	20	7061
  BCL11A-5506	-	GAGCUCUAAUCCCCACGCCU	20	7062
  BCL11A-5507	+	AAGAAUGGCUUCAAGAGGCU	20	7063
  BCL11A-5508	+	GUUGUACAUGUGUAGCUGCU	20	7064
  BCL11A-5509	+	UUCCCGUUUGCUUAAGUGCU	20	7065
  BCL11A-5510	+	UCUGCACUCAUCCCAGGCGU	20	7066
  BCL11A-5511	-	UGCCAGAUGAACUUCCCAUU	20	7067
  BCL11A-5512	-	GAACCAGACCACGGCCCGUU	20	7068
  BCL11A-5513	+	ACCUGCUAUGUGUUCCUGUU	20	7069
  BCL11A-5514	+	CCUGCUAUGUGUUCCUGUUU	20	7070

• Table 15C 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 500 bp of coding sequence (e.g., anywhere from +500 (relative to the start codon) to the stop codon of the gene). It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

• TABLE 15C
  3rd Tier

  	DNA		Target Site	SEQ ID
  gRNA Name	Strand	Targeting Domain	Length	NO:
  BCL11A-5515	+	UCCGACGAGGAGGCAAA	17	7071
  BCL11A-5516	+	AUUCUUAGCAGGUUAAA	17	7072
  BCL11A-5517	-	GCUGCGGUUGAAUCCAA	17	7073
  BCL11A-5518	-	GGCCCAGCCCUAUGCAA	17	7074
  BCL11A-5519	+	CCGCAGCACCCUGUCAA	17	7075
  BCL11A-5520	-	CUUCCGGCCUGGCAGAA	17	7076
  BCL11A-5521	+	UUGAUGCGCUUAGAGAA	17	7077
  BCL11A-5522	-	AACCUGAUCCCGGAGAA	17	7078
  BCL11A-5523	-	GAGCACUCCUCGGAGAA	17	7079
  BCL11A-5524	+	CUGGGUACUACGCCGAA	17	7080
  BCL11A-5525	+	UCUCCGAAGCUAAGGAA	17	7081
  BCL11A-5526	+	GGGGGCGUCGCCAGGAA	17	7082
  BCL11A-5527	+	UUGCUACCUGGCUGGAA	17	7083
  BCL11A-5528	+	CUGCACCUAGUCCUGAA	17	7084
  BCL11A-5529	+	AACCAUGCACUGGUGAA	17	7085
  BCL11A-5530	+	AUUUUCUCAGAACUUAA	17	7086
  BCL11A-5531	+	UAUUCUUAGCAGGUUAA	17	7087
  BCL11A-5532	-	GACGAUGGCACUGUUAA	17	7088
  BCL11A-5533	+	CGGUGGUGGACUAAACA	17	7089
  BCL11A-5534	-	GGCCGCGAUGCCCAACA	17	7090
  BCL11A-5535	-	UACUUAGAAAGCGAACA	17	7091
  BCL11A-2969	-	GCACCGGCGCAGCCACA	17	7092
  BCL11A-2924	-	CGAGGCCGAGGGCCACA	17	7093
  BCL11A-5536	-	CCCGAGUGCCUUUGACA	17	7094
  BCL11A-5537	+	CUUGAACUUGGCCACCA	17	7095
  BCL11A-5538	-	AAAAUUUGAAGCCCCCA	17	7096
  BCL11A-5539	+	CUGCAAUAUGAAUCCCA	17	7097
  BCL11A-5540	-	UAUGGAGCCUCCCGCCA	17	7098
  BCL11A-5541	+	CGGGUGAUGGGUGGCCA	17	7099
  BCL11A-5542	+	UCUCCUAGAGAAAUCCA	17	7100
  BCL11A-5543	-	UCCCAGCCACCUCUCCA	17	7101
  BCL11A-5544	-	CUCGGGGCGCAGCGGCA	17	7102
  BCL11A-5545	-	CGACGUCAUGCAGGGCA	17	7103
  BCL11A-5546	+	CUGCAUGACGUCGGGCA	17	7104
  BCL11A-5547	-	GACUUAGAGAGCUGGCA	17	7105
  BCL11A-5548	-	CUGCCCGACGUCAUGCA	17	7106
  BCL11A-5549	+	CUCGCUGAAGUGCUGCA	17	7107
  BCL11A-5550	-	AGCCAUUCACCAGUGCA	17	7108
  BCL11A-5551	-	CACGCACAGAACACUCA	17	7109
  BCL11A-5552	+	GUCGGACUUGACCGUCA	17	7110
  BCL11A-5553	+	ACCAACCCGCGGGGUCA	17	7111
  BCL11A-5554	-	AGGCCCAGCUCAAAAGA	17	7112
  BCL11A-5555	-	GCUUCCGGCCUGGCAGA	17	7113
  BCL11A-5556	-	CCUGGGGGCGGAAGAGA	17	7114
  BCL11A-5557	+	CUUGAUGCGCUUAGAGA	17	7115
  BCL11A-5558	-	GCUGACGGAGAGCGAGA	17	7116
  BCL11A-5559	-	GCGCAUCAAGCUCGAGA	17	7117
  BCL11A-5560	-	UCGGACCGCAUAGACGA	17	7118
  BCL11A-5561	-	ACGGUCAAGUCCGACGA	17	7119
  BCL11A-5562	-	CACCUGGCCGAGGCCGA	17	7120
  BCL11A-5563	+	GUCUCCGAAGCUAAGGA	17	7121
  BCL11A-5564	+	GGGGGGCGUCGCCAGGA	17	7122
  BCL11A-5565	+	AGGUUGGAGACAGAGGA	17	7123
  BCL11A-5566	+	GGGCGGAUUGCAGAGGA	17	7124
  BCL11A-5567	+	GGGGCUGGGAGGGAGGA	17	7125
  BCL11A-5568	-	CCGGGGAGCUGGACGGA	17	7126
  BCL11A-5569	-	GUGUGGCAGUUUUCGGA	17	7127
  BCL11A-5570	+	GGAUUGCAGAGGAGGGA	17	7128
  BCL11A-5571	+	UUGACCGGGGGCUGGGA	17	7129
  BCL11A-5572	+	UGGAGAGGUGGCUGGGA	17	7130
  BCL11A-5573	-	CCGCCCGGGGAGCUGGA	17	7131
  BCL11A-5574	-	GCGGCACGGGAAGUGGA	17	7132
  BCL11A-5575	+	GCCCAGGACCUGGUGGA	17	7133
  BCL11A-5576	-	CAAAUCGUCCCCCAUGA	17	7134
  BCL11A-5577	+	UCUGCACCUAGUCCUGA	17	7135
  BCL11A-5578	-	GGAGGAGGAGGAGCUGA	17	7136
  BCL11A-5579	+	CAAAGGCACUCGGGUGA	17	7137
  BCL11A-5580	+	GGCCCGGACCACUAAUA	17	7138
  BCL11A-5581	+	GCAGUAACCUUUGCAUA	17	7139
  BCL11A-5582	-	AGCGAGAGGGUGGACUA	17	7140
  BCL11A-5583	+	UGGAGUCUCCGAAGCUA	17	7141
  BCL11A-5584	-	GUUGAAUCCAAUGGCUA	17	7142
  BCL11A-5585	+	CACAGGUUGCACUUGUA	17	7143
  BCL11A-5586	+	AAUUUUCUCAGAACUUA	17	7144
  BCL11A-5587	+	UCGGUGGUGGACUAAAC	17	7145
  BCL11A-5588	-	ACCUGAUCCCGGAGAAC	17	7146
  BCL11A-5589	-	AGCACUCCUCGGAGAAC	17	7147
  BCL11A-2979	-	CACCGGCGCAGCCACAC	17	7148
  BCL11A-2916	-	CCGAGGCCGAGGGCCAC	17	7149
  BCL11A-5590	+	UGCACGCGUGGUCGCAC	17	7150
  BCL11A-5591	-	UCGGGGCGCAGCGGCAC	17	7151
  BCL11A-5592	+	CAAGAGAAACCAUGCAC	17	7152
  BCL11A-5593	-	GCAACCUGGUGGUGCAC	17	7153
  BCL11A-5594	+	GCAGCAGCUUUUUGGAC	17	7154
  BCL11A-5595	+	CAUGACUUGGACUUGAC	17	7155
  BCL11A-5596	-	ACCCGAGUGCCUUUGAC	17	7156
  BCL11A-5597	-	CAAAUUUCAGAGCAACC	17	7157
  BCL11A-5598	-	GCCAGCUCCCCGGAACC	17	7158
  BCL11A-5599	+	UGCGCCGGUGCACCACC	17	7159
  BCL11A-5600	-	GCAUAAGCGCGGCCACC	17	7160
  BCL11A-5601	-	CAGCGAGGCCUUCCACC	17	7161
  BCL11A-5602	+	GCUUCUCGCCCAGGACC	17	7162
  BCL11A-5603	+	AUGACUUGGACUUGACC	17	7163
  BCL11A-5604	-	AACCUGCUAAGAAUACC	17	7164
  BCL11A-5605	+	AAGGGCGGCUUGCUACC	17	7165
  BCL11A-5606	-	CGACCACGCGUGCACCC	17	7166
  BCL11A-5607	-	GAAAAUUUGAAGCCCCC	17	7167
  BCL11A-5608	+	CCAUCUCUUCCGCCCCC	17	7168
  BCL11A-5609	-	UCCUCCCUCCCAGCCCC	17	7169
  BCL11A-5610	-	GGAGUUCGACCUGCCCC	17	7170
  BCL11A-5611	+	CCUCCGUCCAGCUCCCC	17	7171
  BCL11A-5612	-	GGCCGCGGCUGCUCCCC	17	7172
  BCL11A-5613	-	AGCCCACCGCUGUCCCC	17	7173
  BCL11A-5614	-	GCUUCUCCACACCGCCC	17	7174
  BCL11A-5615	+	CCGAGGCCGACUCGCCC	17	7175
  BCL11A-5616	+	GCUUAUGCUUCUCGCCC	17	7176
  BCL11A-5617	-	AUUAGUGGUCCGGGCCC	17	7177
  BCL11A-5618	-	GGCGGAAGAGAUGGCCC	17	7178
  BCL11A-5619	+	UUGAGCUGGGCCUGCCC	17	7179
  BCL11A-5620	-	CUCCACCGCCAGCUCCC	17	7180
  BCL11A-5621	+	CCCUCCGUCCAGCUCCC	17	7181
  BCL11A-5622	-	UGGCCGCGGCUGCUCCC	17	7182
  BCL11A-5623	-	CUGCAACCAUUCCAGCC	17	7183
  BCL11A-5624	-	CGGCUUCGGGCUGAGCC	17	7184
  BCL11A-5625	-	CGCUUCUCCACACCGCC	17	7185
  BCL11A-5626	-	CCACCGCAUAGAGCGCC	17	7186
  BCL11A-5627	+	CCCGAGGCCGACUCGCC	17	7187
  BCL11A-5628	+	GGAGGGGGGGCGUCGCC	17	7188
  BCL11A-5629	+	AUAGGGCUGGGCCGGCC	17	7189
  BCL11A-5630	-	GAGAGAGGCUUCCGGCC	17	7190
  BCL11A-5631	+	UGUUGGGCAUCGCGGCC	17	7191
  BCL11A-5632	+	GGCCCUCGGCCUCGGCC	17	7192
  BCL11A-5633	+	CUGGGCCUGCCCGGGCC	17	7193
  BCL11A-5634	-	UAUUAGUGGUCCGGGCC	17	7194
  BCL11A-5635	+	GCUUCAGCUUGCUGGCC	17	7195
  BCL11A-5636	+	UCGGGUGAUGGGUGGCC	17	7196
  BCL11A-5637	+	UUUGAGCUGGGCCUGCC	17	7197
  BCL11A-5638	+	GGGAUCUUUGAGCUGCC	17	7198
  BCL11A-5639	+	GAAAGCGCCCUUCUGCC	17	7199
  BCL11A-5640	+	ACCAAGUCGCUGGUGCC	17	7200
  BCL11A-5641	+	UCUCUCGAUACUGAUCC	17	7201
  BCL11A-5642	-	CGACCCCAACCUGAUCC	17	7202
  BCL11A-5643	+	GGUGGCGCGCCGCCUCC	17	7203
  BCL11A-5644	-	CCGGCUACGCGGCCUCC	17	7204
  BCL11A-5645	+	CCUCGUCCCCGUUCUCC	17	7205
  BCL11A-5646	-	GGCCUUCCACCAGGUCC	17	7206
  BCL11A-5647	-	CCCCAUAUUAGUGGUCC	17	7207
  BCL11A-5648	-	UAGCAAGCCGCCCUUCC	17	7208
  BCL11A-5649	+	CGCUGGUGCCGGGUUCC	17	7209
  BCL11A-5650	-	UAGGAGACUUAGAGAGC	17	7210
  BCL11A-5651	+	GAAGGGGCUCAGCGAGC	17	7211
  BCL11A-2886	-	CACACCGCCCGGGGAGC	17	7212
  BCL11A-5652	+	GCCGGGUUCCGGGGAGC	17	7213
  BCL11A-5653	+	UCUGCCCUCUUUUGAGC	17	7214
  BCL11A-5654	+	CCUGGAGGCCGCGUAGC	17	7215
  BCL11A-5655	+	AUCCUGGUAUUCUUAGC	17	7216
  BCL11A-5656	+	AAGGGAUACCAACCCGC	17	7217
  BCL11A-5657	-	AAGUCCCCUGACCCCGC	17	7218
  BCL11A-5658	+	CGCCCGUGUGGCUGCGC	17	7219
  BCL11A-5659	+	UAUGCGGUCCGACUCGC	17	7220
  BCL11A-5660	-	CCACGAGAACAGCUCGC	17	7221
  BCL11A-5661	-	UACUCGCAGUGGCUCGC	17	7222
  BCL11A-5662	+	GCUGCCCACCAAGUCGC	17	7223
  BCL11A-5663	-	CACCGCUGUCCCCAGGC	17	7224
  BCL11A-5664	+	GCGCCCUUCUGCCAGGC	17	7225
  BCL11A-5665	+	GUGUUGGGCAUCGCGGC	17	7226
  BCL11A-5666	+	UAACCUUUGCAUAGGGC	17	7227
  BCL11A-5667	-	GUGGUCCGGGCCCGGGC	17	7228
  BCL11A-5668	+	CCUGCAUGACGUCGGGC	17	7229
  BCL11A-5669	+	UGGACUUGACCGGGGGC	17	7230
  BCL11A-5670	+	GCAUCGCGGCCGGGGGC	17	7231
  BCL11A-5671	+	UUUGCAUAGGGCUGGGC	17	7232
  BCL11A-5672	+	CUAGAGAAAUCCAUGGC	17	7233
  BCL11A-5673	+	GCGGCUUGCUACCUGGC	17	7234
  BCL11A-5674	-	AGACUUAGAGAGCUGGC	17	7235
  BCL11A-5675	+	UCCCAUGGAGAGGUGGC	17	7236
  BCL11A-5676	-	GACGAAGACUCGGUGGC	17	7237
  BCL11A-5677	-	CCUGCCCGACGUCAUGC	17	7238
  BCL11A-5394	+	UGUACAUGUGUAGCUGC	17	7239
  BCL11A-5678	+	GGACUUGAGCGCGCUGC	17	7240
  BCL11A-5679	-	GUCCAAAAAGCUGCUGC	17	7241
  BCL11A-5680	+	CACCAAGUCGCUGGUGC	17	7242
  BCL11A-5681	+	GUGGCGCUUCAGCUUGC	17	7243
  BCL11A-5682	+	CCCCGUUCUCCGGGAUC	17	7244
  BCL11A-5683	+	CCCUGUCAAAGGCACUC	17	7245
  BCL11A-5684	-	CCGGGCGAGUCGGCCUC	17	7246
  BCL11A-5685	-	CUGGACGGAGGGAUCUC	17	7247
  BCL11A-5686	+	ACACAUCUUGAGCUCUC	17	7248
  BCL11A-5687	+	UCCUCGUCCCCGUUCUC	17	7249
  BCL11A-5688	+	AUGCCCUGCAUGACGUC	17	7250
  BCL11A-5689	+	UACCAACCCGCGGGGUC	17	7251
  BCL11A-5690	-	GCCCCAUAUUAGUGGUC	17	7252
  BCL11A-5691	+	GGCAAAAGGCGAUUGUC	17	7253
  BCL11A-5692	-	CGGGUUGGUAUCCCUUC	17	7254
  BCL11A-5693	-	GUAUCGAGAGAGGCUUC	17	7255
  BCL11A-5694	-	GGGUGGACUACGGCUUC	17	7256
  BCL11A-5695	+	UCGCUGGUGCCGGGUUC	17	7257
  BCL11A-5696	-	CAGGCCCAGCUCAAAAG	17	7258
  BCL11A-5697	+	GUGAAGAACCUAGAAAG	17	7259
  BCL11A-5698	+	UUCUUAGCAGGUUAAAG	17	7260
  BCL11A-3087	-	CGAGGAAGAGGAAGAAG	17	7261
  BCL11A-5699	+	UGAUGCGCUUAGAGAAG	17	7262
  BCL11A-3083	-	GGAGGACGACGAGGAAG	17	7263
  BCL11A-3089	-	GGAAGAAGAGGAGGAAG	17	7264
  BCL11A-3075	-	CGGGGACGAGGAGGAAG	17	7265
  BCL11A-2876	-	CGCAGCGGCACGGGAAG	17	7266
  BCL11A-5700	+	GGUGGUGGACUAAACAG	17	7267
  BCL11A-5701	+	AAAGAGGUUGGAGACAG	17	7268
  BCL11A-5702	+	GGCCGGCCUGGGGACAG	17	7269
  BCL11A-5703	-	AAAUUUGAAGCCCCCAG	17	7270
  BCL11A-5704	-	GGGAUCUCGGGGCGCAG	17	7271
  BCL11A-5705	-	AGAACGUGUACUCGCAG	17	7272
  BCL11A-5706	+	GGAGGGGCGGAUUGCAG	17	7273
  BCL11A-5707	+	CCAACCCGCGGGGUCAG	17	7274
  BCL11A-5708	-	AGGAUCAGUAUCGAGAG	17	7275
  BCL11A-5709	-	AGCUGACGGAGAGCGAG	17	7276
  BCL11A-5710	+	GGUUGGAGACAGAGGAG	17	7277
  BCL11A-5711	+	GGGCUGGGAGGGAGGAG	17	7278
  BCL11A-5712	+	GAUUGCAGAGGAGGGAG	17	7279
  BCL11A-5713	+	ACUAAACAGGGGGGGAG	17	7280
  BCL11A-5714	+	AUAUGAAUCCCAUGGAG	17	7281
  BCL11A-5715	-	AGCACGCCCCAUAUUAG	17	7282
  BCL11A-5716	-	CCUGAUCCCGGAGAACG	17	7283
  BCL11A-3081	-	GGAAGAGGAGGACGACG	17	7284
  BCL11A-5717	+	CGAGGAGUGCUCCGACG	17	7285
  BCL11A-2837	-	CCCGGAGAACGGGGACG	17	7286
  BCL11A-5718	-	GUGGCUCGCCGGCUACG	17	7287
  BCL11A-5719	+	UGACUUGGACUUGACCG	17	7288
  BCL11A-5720	+	GAAGGGAUACCAACCCG	17	7289
  BCL11A-5721	-	GAAGUCCCCUGACCCCG	17	7290
  BCL11A-5722	+	UUUGGACAGGCCCCCCG	17	7291
  BCL11A-5723	-	CUUCUCCACACCGCCCG	17	7292
  BCL11A-5724	+	CGAGGCCGACUCGCCCG	17	7293
  BCL11A-2946	+	CGCCCGGGGAGCAGCCG	17	7294
  BCL11A-5725	-	CCACCUGGCCGAGGCCG	17	7295
  BCL11A-5726	+	GUUGGGCAUCGCGGCCG	17	7296
  BCL11A-5727	-	GGCACUGUUAAUGGCCG	17	7297
  BCL11A-5728	-	GCGCGGCCACCUGGCCG	17	7298
  BCL11A-5729	+	CAAACUCCCGUUCUCCG	17	7299
  BCL11A-5730	-	CAGCGCGCUCAAGUCCG	17	7300
  BCL11A-5731	+	GCUGGUGCCGGGUUCCG	17	7301
  BCL11A-5732	-	GGCGAGAAGCAUAAGCG	17	7302
  BCL11A-5733	-	CAUGCAGCACUUCAGCG	17	7303
  BCL11A-5734	+	UGGCCUGGGUGCACGCG	17	7304
  BCL11A-5735	+	AGGGAUACCAACCCGCG	17	7305
  BCL11A-5736	-	CACGAGAACAGCUCGCG	17	7306
  BCL11A-5737	+	UGACGUCGGGCAGGGCG	17	7307
  BCL11A-5738	-	GAACAGCUCGCGGGGCG	17	7308
  BCL11A-5739	-	GGGCGCGGUCGUGGGCG	17	7309
  BCL11A-5740	+	CUCCGUGUUGGGCAUCG	17	7310
  BCL11A-5741	-	CGGGCGAGUCGGCCUCG	17	7311
  BCL11A-5742	-	ACCACGAGAACAGCUCG	17	7312
  BCL11A-5743	-	UGGACGGAGGGAUCUCG	17	7313
  BCL11A-5744	+	CCCGCGAGCUGUUCUCG	17	7314
  BCL11A-5745	-	CUCGCGGGGCGCGGUCG	17	7315
  BCL11A-5746	+	GUGGUGGACUAAACAGG	17	7316
  BCL11A-5747	+	CCUCGGCCUCGGCCAGG	17	7317
  BCL11A-3090	-	GGAAGAGGAAGAAGAGG	17	7318
  BCL11A-3091	-	AGAAGAGGAGGAAGAGG	17	7319
  BCL11A-3088	-	GGACGAGGAGGAAGAGG	17	7320
  BCL11A-5748	+	GAGGUUGGAGACAGAGG	17	7321
  BCL11A-5749	+	GGGGCGGAUUGCAGAGG	17	7322
  BCL11A-5750	+	UGAAUCCCAUGGAGAGG	17	7323
  BCL11A-5751	+	GGAGUGCUCCGACGAGG	17	7324
  BCL11A-3066	-	GGAGAACGGGGACGAGG	17	7325
  BCL11A-3092	-	AGAGGAGGAAGAGGAGG	17	7326
  BCL11A-5752	+	GUUGGAGACAGAGGAGG	17	7327
  BCL11A-3093	-	GGAGGAAGAGGAGGAGG	17	7328
  BCL11A-5753	+	AUUGCAGAGGAGGGAGG	17	7329
  BCL11A-5754	+	GGGGGCUGGGAGGGAGG	17	7330
  BCL11A-5755	-	CGGGCUGAGCCUGGAGG	17	7331
  BCL11A-5756	-	CCCGGGGAGCUGGACGG	17	7332
  BCL11A-5757	+	GACUUGGACUUGACCGG	17	7333
  BCL11A-5758	+	UUGGGCAUCGCGGCCGG	17	7334
  BCL11A-5759	+	CGGCCUGGGGACAGCGG	17	7335
  BCL11A-5760	+	UUCCGGGGAGCUGGCGG	17	7336
  BCL11A-5761	+	CCAGGCGCUCUAUGCGG	17	7337
  BCL11A-5762	-	UUGCGACGAAGACUCGG	17	7338
  BCL11A-5763	-	GGGCGAGUCGGCCUCGG	17	7339
  BCL11A-5764	+	UCCAAGUGAUGUCUCGG	17	7340
  BCL11A-5765	+	GGCGUCGCCAGGAAGGG	17	7341
  BCL11A-5766	+	UGGUGGACUAAACAGGG	17	7342
  BCL11A-3076	-	GACGGAGAGCGAGAGGG	17	7343
  BCL11A-5767	+	CGGAUUGCAGAGGAGGG	17	7344
  BCL11A-5768	+	UUGCAGAGGAGGGAGGG	17	7345
  BCL11A-5769	+	ACCGGGGGCUGGGAGGG	17	7346
  BCL11A-5770	+	CCGUCCAGCUCCCCGGG	17	7347
  BCL11A-5771	+	GAGAAAUCCAUGGCGGG	17	7348
  BCL11A-5772	-	GGCGAGUCGGCCUCGGG	17	7349
  BCL11A-5773	+	GGUGGACUAAACAGGGG	17	7350
  BCL11A-5774	-	UUUGAAGCCCCCAGGGG	17	7351
  BCL11A-5775	+	CUGGGAGGGAGGAGGGG	17	7352
  BCL11A-5776	+	UGCAGAGGAGGGAGGGG	17	7353
  BCL11A-5777	-	CAUAGAGCGCCUGGGGG	17	7354
  BCL11A-5778	-	AGCCCCCAGGGGUGGGG	17	7355
  BCL11A-5779	+	GGCACUCGGGUGAUGGG	17	7356
  BCL11A-5780	+	CUUGACCGGGGGCUGGG	17	7357
  BCL11A-5781	+	AACAGGGGGGGAGUGGG	17	7358
  BCL11A-5782	+	GGUACUACGCCGAAUGG	17	7359
  BCL11A-5783	+	CCUAGAGAAAUCCAUGG	17	7360
  BCL11A-5784	+	GGACUUGACCGUCAUGG	17	7361
  BCL11A-5785	-	AUUUCAGAGCAACCUGG	17	7362
  BCL11A-5786	+	UCUCGCCCAGGACCUGG	17	7363
  BCL11A-5787	-	CUUCGGGCUGAGCCUGG	17	7364
  BCL11A-5788	-	CCGCAUAGAGCGCCUGG	17	7365
  BCL11A-5789	+	AUCUUUGAGCUGCCUGG	17	7366
  BCL11A-5790	+	GGGUUCCGGGGAGCUGG	17	7367
  BCL11A-5791	-	AGCGGCACGGGAAGUGG	17	7368
  BCL11A-5792	-	CGCGCUCAAGUCCGUGG	17	7369
  BCL11A-5793	+	GCGAGCUGUUCUCGUGG	17	7370
  BCL11A-5794	+	GGCGCUCUAUGCGGUGG	17	7371
  BCL11A-5795	+	AAGUGAUGUCUCGGUGG	17	7372
  BCL11A-5796	-	CGGCACCAGCGACUUGG	17	7373
  BCL11A-5797	+	GGGUACUACGCCGAAUG	17	7374
  BCL11A-5798	+	CGGACUUGACCGUCAUG	17	7375
  BCL11A-5799	+	GCAUGUGCGUCUUCAUG	17	7376
  BCL11A-5800	+	CCCGGACCACUAAUAUG	17	7377
  BCL11A-5801	+	CCCCCAGGCGCUCUAUG	17	7378
  BCL11A-5802	+	CAGUGCCAUCGUCUAUG	17	7379
  BCL11A-5803	-	GACACUUGUGAGUACUG	17	7380
  BCL11A-5804	+	CGUCGCAAGUGUCCCUG	17	7381
  BCL11A-5805	-	ACCGCAUAGAGCGCCUG	17	7382
  BCL11A-5806	+	AGGGCUGGGCCGGCCUG	17	7383
  BCL11A-5807	+	AGGGGCUCAGCGAGCUG	17	7384
  BCL11A-5808	-	CCUUUGACAGGGUGCUG	17	7385
  BCL11A-5809	-	AAGUCAUGCGAGUUCUG	17	7386
  BCL11A-5810	+	AGGGCUUCUCGCCCGUG	17	7387
  BCL11A-5811	+	CAGCUCCCCGGGCGGUG	17	7388
  BCL11A-5812	+	AGGCGCUCUAUGCGGUG	17	7389
  BCL11A-5813	-	UGAAGCCCCCAGGGGUG	17	7390
  BCL11A-5814	-	AGAGAGCUCAAGAUGUG	17	7391
  BCL11A-5815	+	UCUCCGGGAUCAGGUUG	17	7392
  BCL11A-5816	+	UGGGUACUACGCCGAAU	17	7393
  BCL11A-5817	+	GGAGGCUCCAUAGCCAU	17	7394
  BCL11A-5818	-	CCCAGCCACCUCUCCAU	17	7395
  BCL11A-5819	+	UGCAGUAACCUUUGCAU	17	7396
  BCL11A-5820	+	UCGGACUUGACCGUCAU	17	7397
  BCL11A-5821	+	AAAGGCACUCGGGUGAU	17	7398
  BCL11A-5822	+	GCCCGGACCACUAAUAU	17	7399
  BCL11A-5823	+	GUUCUCGCUCUUGAACU	17	7400
  BCL11A-5824	+	ACCCUGUCAAAGGCACU	17	7401
  BCL11A-5825	-	ACCACCGAGACAUCACU	17	7402
  BCL11A-5826	-	CACUUGCGACGAAGACU	17	7403
  BCL11A-5827	-	ACCCGGCACCAGCGACU	17	7404
  BCL11A-5828	-	GGUAUCCCUUCAGGACU	17	7405
  BCL11A-5829	+	GCAGAACUCGCAUGACU	17	7406
  BCL11A-5830	+	AGUGUCCCUGUGGCCCU	17	7407
  BCL11A-5831	-	CACCGCAUAGAGCGCCU	17	7408
  BCL11A-5832	+	UAGGGCUGGGCCGGCCU	17	7409
  BCL11A-5833	+	CCUGUGGCCCUCGGCCU	17	7410
  BCL11A-5834	-	CCCGGGCGAGUCGGCCU	17	7411
  BCL11A-5835	+	CUUCAGCUUGCUGGCCU	17	7412
  BCL11A-5836	-	CUCGUCGGAGCACUCCU	17	7413
  BCL11A-5837	-	GCCUUCCACCAGGUCCU	17	7414
  BCL11A-5838	+	AAGGGGCUCAGCGAGCU	17	7415
  BCL11A-5839	+	CUGCCCUCUUUUGAGCU	17	7416
  BCL11A-5840	+	AACCUUUGCAUAGGGCU	17	7417
  BCL11A-5841	+	GGACUUGACCGGGGGCU	17	7418
  BCL11A-5842	+	CCCAUGGAGAGGUGGCU	17	7419
  BCL11A-5434	+	GUACAUGUGUAGCUGCU	17	7420
  BCL11A-5843	-	UCCAAAAAGCUGCUGCU	17	7421
  BCL11A-5844	-	GCUGGACGGAGGGAUCU	17	7422
  BCL11A-5845	+	CACAUCUUGAGCUCUCU	17	7423
  BCL11A-5846	-	CCGCCAUGGAUUUCUCU	17	7424
  BCL11A-5847	+	GGGUCCAAGUGAUGUCU	17	7425
  BCL11A-5848	-	GUCUCCAACCUCUUUCU	17	7426
  BCL11A-5849	-	CUCGGUGGCCGGCGAGU	17	7427
  BCL11A-5850	-	CUGCUCCCCGGGCGAGU	17	7428
  BCL11A-5851	+	CUAAACAGGGGGGGAGU	17	7429
  BCL11A-5852	+	CAUGCCCUGCAUGACGU	17	7430
  BCL11A-5853	-	GGCGCGGUCGUGGGCGU	17	7431
  BCL11A-5854	-	GCCUUUUGCCUCCUCGU	17	7432
  BCL11A-5855	+	GGUGGAGAGACCGUCGU	17	7433
  BCL11A-5856	-	UCGCGGGGCGCGGUCGU	17	7434
  BCL11A-5857	+	GUUCUCCGGGAUCAGGU	17	7435
  BCL11A-5858	+	AGAACCUAGAAAGAGGU	17	7436
  BCL11A-5859	+	GGCCUGGGGACAGCGGU	17	7437
  BCL11A-5860	+	CAGGCGCUCUAUGCGGU	17	7438
  BCL11A-5861	-	CCCCUGACCCCGCGGGU	17	7439
  BCL11A-5862	-	UUGAAGCCCCCAGGGGU	17	7440
  BCL11A-5863	-	GGCACCAGCGACUUGGU	17	7441
  BCL11A-5864	-	ACACUUGUGAGUACUGU	17	7442
  BCL11A-5865	+	GUACACGUUCUCCGUGU	17	7443
  BCL11A-5866	+	GCACAGGUUGCACUUGU	17	7444
  BCL11A-5867	-	CUUCACACACCCCCAUU	17	7445
  BCL11A-5868	-	GAUCCCUUCCUUAGCUU	17	7446
  BCL11A-5869	-	AGGGUGGACUACGGCUU	17	7447
  BCL11A-5870	+	UUCUCCGGGAUCAGGUU	17	7448
  BCL11A-5871	+	UACACGUUCUCCGUGUU	17	7449
  BCL11A-5872	+	GCCCAGCAGCAGCUUUU	17	7450
  BCL11A-5873	-	AGAUGUGUGGCAGUUUU	17	7451
  BCL11A-5874	+	UGCUCCGACGAGGAGGCAAA	20	7452
  BCL11A-5875	+	GGUAUUCUUAGCAGGUUAAA	20	7453
  BCL11A-5876	-	GGUGCUGCGGUUGAAUCCAA	20	7454
  BCL11A-5877	-	GCCGGCCCAGCCCUAUGCAA	20	7455
  BCL11A-5878	+	CAACCGCAGCACCCUGUCAA	20	7456
  BCL11A-5879	-	AGGCUUCCGGCCUGGCAGAA	20	7457
  BCL11A-5880	+	AGCUUGAUGCGCUUAGAGAA	20	7458
  BCL11A-5881	-	CCCAACCUGAUCCCGGAGAA	20	7459
  BCL11A-5882	-	UCGGAGCACUCCUCGGAGAA	20	7460
  BCL11A-5883	+	UCUCUGGGUACUACGCCGAA	20	7461
  BCL11A-5884	+	GAGUCUCCGAAGCUAAGGAA	20	7462
  BCL11A-5885	+	AGGGGGGGCGUCGCCAGGAA	20	7463
  BCL11A-5886	+	GGCUUGCUACCUGGCUGGAA	20	7464
  BCL11A-5887	+	AUUCUGCACCUAGUCCUGAA	20	7465
  BCL11A-5888	+	AGAAACCAUGCACUGGUGAA	20	7466
  BCL11A-5889	+	CAAAUUUUCUCAGAACUUAA	20	7467
  BCL11A-5890	+	UGGUAUUCUUAGCAGGUUAA	20	7468
  BCL11A-5891	-	AUAGACGAUGGCACUGUUAA	20	7469
  BCL11A-5892	+	UCUCGGUGGUGGACUAAACA	20	7470
  BCL11A-5893	-	CCCGGCCGCGAUGCCCAACA	20	7471
  BCL11A-5894	-	AUCUACUUAGAAAGCGAACA	20	7472
  BCL11A-5895	-	GGUGCACCGGCGCAGCCACA	20	7473
  BCL11A-3377	-	GGCCGAGGCCGAGGGCCACA	20	7474
  BCL11A-5896	-	UCACCCGAGUGCCUUUGACA	20	7475
  BCL11A-5897	+	GCUCUUGAACUUGGCCACCA	20	7476
  BCL11A-5898	-	GAGAAAAUUUGAAGCCCCCA	20	7477
  BCL11A-5899	+	UGUCUGCAAUAUGAAUCCCA	20	7478
  BCL11A-5900	-	GGCUAUGGAGCCUCCCGCCA	20	7479
  BCL11A-5901	+	ACUCGGGUGAUGGGUGGCCA	20	7480
  BCL11A-5902	+	AAGUCUCCUAGAGAAAUCCA	20	7481
  BCL11A-5903	-	CCUUCCCAGCCACCUCUCCA	20	7482
  BCL11A-5904	-	GAUCUCGGGGCGCAGCGGCA	20	7483
  BCL11A-5905	-	GCCCGACGUCAUGCAGGGCA	20	7484
  BCL11A-5906	+	GCCCUGCAUGACGUCGGGCA	20	7485
  BCL11A-5907	-	GGAGACUUAGAGAGCUGGCA	20	7486
  BCL11A-5908	-	GCCCUGCCCGACGUCAUGCA	20	7487
  BCL11A-5909	+	GGCCUCGCUGAAGUGCUGCA	20	7488
  BCL11A-5910	-	AACAGCCAUUCACCAGUGCA	20	7489
  BCL11A-5911	-	CAACACGCACAGAACACUCA	20	7490
  BCL11A-5912	+	GUCGUCGGACUUGACCGUCA	20	7491
  BCL11A-5913	+	GAUACCAACCCGCGGGGUCA	20	7492
  BCL11A-5914	-	GGCAGGCCCAGCUCAAAAGA	20	7493
  BCL11A-5915	-	GAGGCUUCCGGCCUGGCAGA	20	7494
  BCL11A-5916	-	GCGCCUGGGGGCGGAAGAGA	20	7495
  BCL11A-5917	+	GAGCUUGAUGCGCUUAGAGA	20	7496
  BCL11A-5918	-	GGAGCUGACGGAGAGCGAGA	20	7497
  BCL11A-5919	-	UAAGCGCAUCAAGCUCGAGA	20	7498
  BCL11A-5920	-	GAGUCGGACCGCAUAGACGA	20	7499
  BCL11A-5921	-	AUGACGGUCAAGUCCGACGA	20	7500
  BCL11A-5922	-	GGCCACCUGGCCGAGGCCGA	20	7501
  BCL11A-5923	+	GGAGUCUCCGAAGCUAAGGA	20	7502
  BCL11A-5924	+	GAGGGGGGGCGUCGCCAGGA	20	7503
  BCL11A-5925	+	AAGAGGUUGGAGACAGAGGA	20	7504
  BCL11A-5926	+	GAGGGGCGGAUUGCAGAGGA	20	7505
  BCL11A-5927	+	CCGGGGGCUGGGAGGGAGGA	20	7506
  BCL11A-5928	-	CGCCCGGGGAGCUGGACGGA	20	7507
  BCL11A-5929	-	GAUGUGUGGCAGUUUUCGGA	20	7508
  BCL11A-5930	+	GGCGGAUUGCAGAGGAGGGA	20	7509
  BCL11A-5931	+	GACUUGACCGGGGGCUGGGA	20	7510
  BCL11A-5932	+	CCAUGGAGAGGUGGCUGGGA	20	7511
  BCL11A-5933	-	ACACCGCCCGGGGAGCUGGA	20	7512
  BCL11A-5934	-	GCAGCGGCACGGGAAGUGGA	20	7513
  BCL11A-5935	+	CUCGCCCAGGACCUGGUGGA	20	7514
  BCL11A-5936	-	GCACAAAUCGUCCCCCAUGA	20	7515
  BCL11A-5937	+	CAUUCUGCACCUAGUCCUGA	20	7516
  BCL11A-5938	-	AGAGGAGGAGGAGGAGCUGA	20	7517
  BCL11A-5939	+	UGUCAAAGGCACUCGGGUGA	20	7518
  BCL11A-5940	+	CCGGGCCCGGACCACUAAUA	20	7519
  BCL11A-5941	+	GUUGCAGUAACCUUUGCAUA	20	7520
  BCL11A-5942	-	GAGAGCGAGAGGGUGGACUA	20	7521
  BCL11A-5943	+	GUCUGGAGUCUCCGAAGCUA	20	7522
  BCL11A-5944	-	GCGGUUGAAUCCAAUGGCUA	20	7523
  BCL11A-5945	+	UCGCACAGGUUGCACUUGUA	20	7524
  BCL11A-5946	+	UCAAAUUUUCUCAGAACUUA	20	7525
  BCL11A-5947	+	GUCUCGGUGGUGGACUAAAC	20	7526
  BCL11A-5948	-	CCAACCUGAUCCCGGAGAAC	20	7527
  BCL11A-5949	-	CGGAGCACUCCUCGGAGAAC	20	7528
  BCL11A-5950	-	GUGCACCGGCGCAGCCACAC	20	7529
  BCL11A-5951	-	UGGCCGAGGCCGAGGGCCAC	20	7530
  BCL11A-5952	+	GGGUGCACGCGUGGUCGCAC	20	7531
  BCL11A-5953	-	AUCUCGGGGCGCAGCGGCAC	20	7532
  BCL11A-5954	+	UUGCAAGAGAAACCAUGCAC	20	7533
  BCL11A-5955	-	AGAGCAACCUGGUGGUGCAC	20	7534
  BCL11A-5956	+	CCAGCAGCAGCUUUUUGGAC	20	7535
  BCL11A-5957	+	UCGCAUGACUUGGACUUGAC	20	7536
  BCL11A-5958	-	AUCACCCGAGUGCCUUUGAC	20	7537
  BCL11A-5959	-	GUUCAAAUUUCAGAGCAACC	20	7538
  BCL11A-5960	-	ACCGCCAGCUCCCCGGAACC	20	7539
  BCL11A-5961	+	GGCUGCGCCGGUGCACCACC	20	7540
  BCL11A-5962	-	GAAGCAUAAGCGCGGCCACC	20	7541
  BCL11A-5963	-	CUUCAGCGAGGCCUUCCACC	20	7542
  BCL11A-5964	+	UAUGCUUCUCGCCCAGGACC	20	7543
  BCL11A-5965	+	CGCAUGACUUGGACUUGACC	20	7544
  BCL11A-5966	-	UUUAACCUGCUAAGAAUACC	20	7545
  BCL11A-5967	+	AGGAAGGGCGGCUUGCUACC	20	7546
  BCL11A-5968	-	GUGCGACCACGCGUGCACCC	20	7547
  BCL11A-5969	-	UGAGAAAAUUUGAAGCCCCC	20	7548
  BCL11A-5970	+	GGGCCAUCUCUUCCGCCCCC	20	7549
  BCL11A-5971	-	CCCUCCUCCCUCCCAGCCCC	20	7550
  BCL11A-5972	-	GAAGGAGUUCGACCUGCCCC	20	7551
  BCL11A-5973	+	AUCCCUCCGUCCAGCUCCCC	20	7552
  BCL11A-5974	-	AAUGGCCGCGGCUGCUCCCC	20	7553
  BCL11A-5975	-	UCUAGCCCACCGCUGUCCCC	20	7554
  BCL11A-5976	-	UGCGCUUCUCCACACCGCCC	20	7555
  BCL11A-5977	+	CCCCCGAGGCCGACUCGCCC	20	7556
  BCL11A-5978	+	CGCGCUUAUGCUUCUCGCCC	20	7557
  BCL11A-5979	-	CAUAUUAGUGGUCCGGGCCC	20	7558
  BCL11A-5980	-	GGGGGCGGAAGAGAUGGCCC	20	7559
  BCL11A-5981	+	CUUUUGAGCUGGGCCUGCCC	20	7560
  BCL11A-5982	-	UCUCUCCACCGCCAGCUCCC	20	7561
  BCL11A-5983	+	GAUCCCUCCGUCCAGCUCCC	20	7562
  BCL11A-5984	-	UAAUGGCCGCGGCUGCUCCC	20	7563
  BCL11A-5985	-	UUACUGCAACCAUUCCAGCC	20	7564
  BCL11A-5986	-	CUACGGCUUCGGGCUGAGCC	20	7565
  BCL11A-5987	-	UUGCGCUUCUCCACACCGCC	20	7566
  BCL11A-5988	-	CCCCCACCGCAUAGAGCGCC	20	7567
  BCL11A-5989	+	CCCCCCGAGGCCGACUCGCC	20	7568
  BCL11A-5990	+	GAGGGAGGGGGGGCGUCGCC	20	7569
  BCL11A-5991	+	UGCAUAGGGCUGGGCCGGCC	20	7570
  BCL11A-5992	-	AUCGAGAGAGGCUUCCGGCC	20	7571
  BCL11A-5993	+	CCGUGUUGGGCAUCGCGGCC	20	7572
  BCL11A-5994	+	UGUGGCCCUCGGCCUCGGCC	20	7573
  BCL11A-5995	+	GAGCUGGGCCUGCCCGGGCC	20	7574
  BCL11A-5996	-	CCAUAUUAGUGGUCCGGGCC	20	7575
  BCL11A-5997	+	GGCGCUUCAGCUUGCUGGCC	20	7576
  BCL11A-5998	+	CACUCGGGUGAUGGGUGGCC	20	7577
  BCL11A-5999	+	UCUUUUGAGCUGGGCCUGCC	20	7578
  BCL11A-6000	+	GAAGGGAUCUUUGAGCUGCC	20	7579
  BCL11A-6001	+	GUGGAAAGCGCCCUUCUGCC	20	7580
  BCL11A-6002	+	CCCACCAAGUCGCUGGUGCC	20	7581
  BCL11A-6003	+	GCCUCUCUCGAUACUGAUCC	20	7582
  BCL11A-6004	-	GAACGACCCCAACCUGAUCC	20	7583
  BCL11A-6005	+	CGUGGUGGCGCGCCGCCUCC	20	7584
  BCL11A-6006	-	UCGCCGGCUACGCGGCCUCC	20	7585
  BCL11A-6007	+	CCUCCUCGUCCCCGUUCUCC	20	7586
  BCL11A-6008	-	CGAGGCCUUCCACCAGGUCC	20	7587
  BCL11A-6009	-	ACGCCCCAUAUUAGUGGUCC	20	7588
  BCL11A-6010	-	AGGUAGCAAGCCGCCCUUCC	20	7589
  BCL11A-6011	+	AGUCGCUGGUGCCGGGUUCC	20	7590
  BCL11A-6012	-	CUCUAGGAGACUUAGAGAGC	20	7591
  BCL11A-6013	+	AGAGAAGGGGCUCAGCGAGC	20	7592
  BCL11A-6014	-	CUCCACACCGCCCGGGGAGC	20	7593
  BCL11A-6015	+	GGUGCCGGGUUCCGGGGAGC	20	7594
  BCL11A-6016	+	GCGUCUGCCCUCUUUUGAGC	20	7595
  BCL11A-6017	+	CUGCCUGGAGGCCGCGUAGC	20	7596
  BCL11A-6018	+	CUGAUCCUGGUAUUCUUAGC	20	7597
  BCL11A-6019	+	CUGAAGGGAUACCAACCCGC	20	7598
  BCL11A-6020	-	CGGAAGUCCCCUGACCCCGC	20	7599
  BCL11A-6021	+	UCUCGCCCGUGUGGCUGCGC	20	7600
  BCL11A-6022	+	GUCUAUGCGGUCCGACUCGC	20	7601
  BCL11A-6023	-	CCACCACGAGAACAGCUCGC	20	7602
  BCL11A-6024	-	GUGUACUCGCAGUGGCUCGC	20	7603
  BCL11A-6025	+	GGCGCUGCCCACCAAGUCGC	20	7604
  BCL11A-6026	-	GCCCACCGCUGUCCCCAGGC	20	7605
  BCL11A-6027	+	AAAGCGCCCUUCUGCCAGGC	20	7606
  BCL11A-6028	+	UCCGUGUUGGGCAUCGCGGC	20	7607
  BCL11A-6029	+	CAGUAACCUUUGCAUAGGGC	20	7608
  BCL11A-6030	-	UUAGUGGUCCGGGCCCGGGC	20	7609
  BCL11A-6031	+	UGCCCUGCAUGACGUCGGGC	20	7610
  BCL11A-6032	+	ACUUGGACUUGACCGGGGGC	20	7611
  BCL11A-6033	+	UGGGCAUCGCGGCCGGGGGC	20	7612
  BCL11A-6034	+	ACCUUUGCAUAGGGCUGGGC	20	7613
  BCL11A-6035	+	CUCCUAGAGAAAUCCAUGGC	20	7614
  BCL11A-6036	+	AGGGCGGCUUGCUACCUGGC	20	7615
  BCL11A-6037	-	AGGAGACUUAGAGAGCUGGC	20	7616
  BCL11A-6038	+	GAAUCCCAUGGAGAGGUGGC	20	7617
  BCL11A-6039	-	UGCGACGAAGACUCGGUGGC	20	7618
  BCL11A-6040	-	CGCCCUGCCCGACGUCAUGC	20	7619
  BCL11A-5467	+	AGUUGUACAUGUGUAGCUGC	20	7620
  BCL11A-6041	+	CACGGACUUGAGCGCGCUGC	20	7621
  BCL11A-6042	-	CCUGUCCAAAAAGCUGCUGC	20	7622
  BCL11A-6043	+	GCCCACCAAGUCGCUGGUGC	20	7623
  BCL11A-6044	+	CAUGUGGCGCUUCAGCUUGC	20	7624
  BCL11A-6045	+	CGUCCCCGUUCUCCGGGAUC	20	7625
  BCL11A-6046	+	GCACCCUGUCAAAGGCACUC	20	7626
  BCL11A-6047	-	UCCCCGGGCGAGUCGGCCUC	20	7627
  BCL11A-6048	-	GAGCUGGACGGAGGGAUCUC	20	7628
  BCL11A-6049	+	GCCACACAUCUUGAGCUCUC	20	7629
  BCL11A-6050	+	UCCUCCUCGUCCCCGUUCUC	20	7630
  BCL11A-6051	+	ACCAUGCCCUGCAUGACGUC	20	7631
  BCL11A-6052	+	GGAUACCAACCCGCGGGGUC	20	7632
  BCL11A-6053	-	CACGCCCCAUAUUAGUGGUC	20	7633
  BCL11A-6054	+	GGAGGCAAAAGGCGAUUGUC	20	7634
  BCL11A-6055	-	CCGCGGGUUGGUAUCCCUUC	20	7635
  BCL11A-6056	-	UCAGUAUCGAGAGAGGCUUC	20	7636
  BCL11A-6057	-	AGAGGGUGGACUACGGCUUC	20	7637
  BCL11A-6058	+	AAGUCGCUGGUGCCGGGUUC	20	7638
  BCL11A-6059	-	GGGCAGGCCCAGCUCAAAAG	20	7639
  BCL11A-6060	+	UGUGUGAAGAACCUAGAAAG	20	7640
  BCL11A-6061	+	GUAUUCUUAGCAGGUUAAAG	20	7641
  BCL11A-3449	-	CGACGAGGAAGAGGAAGAAG	20	7642
  BCL11A-6062	+	GCUUGAUGCGCUUAGAGAAG	20	7643
  BCL11A-3448	-	AGAGGAGGACGACGAGGAAG	20	7644
  BCL11A-3453	-	AGAGGAAGAAGAGGAGGAAG	20	7645
  BCL11A-3441	-	GAACGGGGACGAGGAGGAAG	20	7646
  BCL11A-3376	-	GGGCGCAGCGGCACGGGAAG	20	7647
  BCL11A-6063	+	CUCGGUGGUGGACUAAACAG	20	7648
  BCL11A-6064	+	UAGAAAGAGGUUGGAGACAG	20	7649
  BCL11A-6065	+	CUGGGCCGGCCUGGGGACAG	20	7650
  BCL11A-6066	-	AGAAAAUUUGAAGCCCCCAG	20	7651
  BCL11A-6067	-	GGAGGGAUCUCGGGGCGCAG	20	7652
  BCL11A-6068	-	CGGAGAACGUGUACUCGCAG	20	7653
  BCL11A-6069	+	GGAGGAGGGGCGGAUUGCAG	20	7654
  BCL11A-6070	+	AUACCAACCCGCGGGGUCAG	20	7655
  BCL11A-6071	-	ACCAGGAUCAGUAUCGAGAG	20	7656
  BCL11A-6072	-	AGGAGCUGACGGAGAGCGAG	20	7657
  BCL11A-6073	+	AGAGGUUGGAGACAGAGGAG	20	7658
  BCL11A-6074	+	CGGGGGCUGGGAGGGAGGAG	20	7659
  BCL11A-6075	+	GCGGAUUGCAGAGGAGGGAG	20	7660
  BCL11A-6076	+	UGGACUAAACAGGGGGGGAG	20	7661
  BCL11A-6077	+	GCAAUAUGAAUCCCAUGGAG	20	7662
  BCL11A-6078	-	GGGAGCACGCCCCAUAUUAG	20	7663
  BCL11A-6079	-	CAACCUGAUCCCGGAGAACG	20	7664
  BCL11A-3450	-	GGAGGAAGAGGAGGACGACG	20	7665
  BCL11A-6080	+	CUCCGAGGAGUGCUCCGACG	20	7666
  BCL11A-6081	-	GAUCCCGGAGAACGGGGACG	20	7667
  BCL11A-6082	-	GCAGUGGCUCGCCGGCUACG	20	7668
  BCL11A-6083	+	GCAUGACUUGGACUUGACCG	20	7669
  BCL11A-6084	+	CCUGAAGGGAUACCAACCCG	20	7670
  BCL11A-6085	-	ACGGAAGUCCCCUGACCCCG	20	7671
  BCL11A-6086	+	CUUUUUGGACAGGCCCCCCG	20	7672
  BCL11A-6087	-	GCGCUUCUCCACACCGCCCG	20	7673
  BCL11A-6088	+	CCCCGAGGCCGACUCGCCCG	20	7674
  BCL11A-6089	+	ACUCGCCCGGGGAGCAGCCG	20	7675
  BCL11A-6090	-	CGGCCACCUGGCCGAGGCCG	20	7676
  BCL11A-6091	+	CGUGUUGGGCAUCGCGGCCG	20	7677
  BCL11A-6092	-	GAUGGCACUGUUAAUGGCCG	20	7678
  BCL11A-6093	-	UAAGCGCGGCCACCUGGCCG	20	7679
  BCL11A-6094	+	GCGCAAACUCCCGUUCUCCG	20	7680
  BCL11A-6095	-	CAGCAGCGCGCUCAAGUCCG	20	7681
  BCL11A-6096	+	GUCGCUGGUGCCGGGUUCCG	20	7682
  BCL11A-6097	-	CUGGGCGAGAAGCAUAAGCG	20	7683
  BCL11A-6098	-	CUCCAUGCAGCACUUCAGCG	20	7684
  BCL11A-6099	+	UGCUGGCCUGGGUGCACGCG	20	7685
  BCL11A-6100	+	UGAAGGGAUACCAACCCGCG	20	7686
  BCL11A-6101	-	CACCACGAGAACAGCUCGCG	20	7687
  BCL11A-6102	+	GCAUGACGUCGGGCAGGGCG	20	7688
  BCL11A-6103	-	CGAGAACAGCUCGCGGGGCG	20	7689
  BCL11A-6104	-	GCGGGGCGCGGUCGUGGGCG	20	7690
  BCL11A-6105	+	GUUCUCCGUGUUGGGCAUCG	20	7691
  BCL11A-6106	-	CCCCGGGCGAGUCGGCCUCG	20	7692
  BCL11A-6107	-	GCCACCACGAGAACAGCUCG	20	7693
  BCL11A-6108	-	AGCUGGACGGAGGGAUCUCG	20	7694
  BCL11A-6109	+	CGCCCCGCGAGCUGUUCUCG	20	7695
  BCL11A-6110	-	CAGCUCGCGGGGCGCGGUCG	20	7696
  BCL11A-6111	+	UCGGUGGUGGACUAAACAGG	20	7697
  BCL11A-6112	+	GGCCCUCGGCCUCGGCCAGG	20	7698
  BCL11A-3451	-	CGAGGAAGAGGAAGAAGAGG	20	7699
  BCL11A-3452	-	GGAAGAAGAGGAGGAAGAGG	20	7700
  BCL11A-3445	-	CGGGGACGAGGAGGAAGAGG	20	7701
  BCL11A-6113	+	AAAGAGGUUGGAGACAGAGG	20	7702
  BCL11A-6114	+	GGAGGGGCGGAUUGCAGAGG	20	7703
  BCL11A-6115	+	AUAUGAAUCCCAUGGAGAGG	20	7704
  BCL11A-6116	+	CGAGGAGUGCUCCGACGAGG	20	7705
  BCL11A-3330	-	CCCGGAGAACGGGGACGAGG	20	7706
  BCL11A-3454	-	AGAAGAGGAGGAAGAGGAGG	20	7707
  BCL11A-6117	+	GAGGUUGGAGACAGAGGAGG	20	7708
  BCL11A-3455	-	AGAGGAGGAAGAGGAGGAGG	20	7709
  BCL11A-6118	+	CGGAUUGCAGAGGAGGGAGG	20	7710
  BCL11A-6119	+	ACCGGGGGCUGGGAGGGAGG	20	7711
  BCL11A-6120	-	CUUCGGGCUGAGCCUGGAGG	20	7712
  BCL11A-6121	-	CCGCCCGGGGAGCUGGACGG	20	7713
  BCL11A-6122	+	CAUGACUUGGACUUGACCGG	20	7714
  BCL11A-6123	+	GUGUUGGGCAUCGCGGCCGG	20	7715
  BCL11A-6124	+	GGCCGGCCUGGGGACAGCGG	20	7716
  BCL11A-6125	+	GGGUUCCGGGGAGCUGGCGG	20	7717
  BCL11A-6126	+	CCCCCAGGCGCUCUAUGCGG	20	7718
  BCL11A-6127	-	CACUUGCGACGAAGACUCGG	20	7719
  BCL11A-6128	-	CCCGGGCGAGUCGGCCUCGG	20	7720
  BCL11A-6129	+	GGGUCCAAGUGAUGUCUCGG	20	7721
  BCL11A-6130	+	GGGGGCGUCGCCAGGAAGGG	20	7722
  BCL11A-6131	+	CGGUGGUGGACUAAACAGGG	20	7723
  BCL11A-6132	-	GCUGACGGAGAGCGAGAGGG	20	7724
  BCL11A-6133	+	GGGCGGAUUGCAGAGGAGGG	20	7725
  BCL11A-6134	+	GGAUUGCAGAGGAGGGAGGG	20	7726
  BCL11A-6135	+	UUGACCGGGGGCUGGGAGGG	20	7727
  BCL11A-6136	+	CCUCCGUCCAGCUCCCCGGG	20	7728
  BCL11A-6137	+	CUAGAGAAAUCCAUGGCGGG	20	7729
  BCL11A-6138	-	CCGGGCGAGUCGGCCUCGGG	20	7730
  BCL11A-6139	+	GGUGGUGGACUAAACAGGGG	20	7731
  BCL11A-6140	-	AAAUUUGAAGCCCCCAGGGG	20	7732
  BCL11A-6141	+	GGGCUGGGAGGGAGGAGGGG	20	7733
  BCL11A-6142	+	GAUUGCAGAGGAGGGAGGGG	20	7734
  BCL11A-6143	-	CCGCAUAGAGCGCCUGGGGG	20	7735
  BCL11A-6144	-	UGAAGCCCCCAGGGGUGGGG	20	7736
  BCL11A-6145	+	AAAGGCACUCGGGUGAUGGG	20	7737
  BCL11A-6146	+	GGACUUGACCGGGGGCUGGG	20	7738
  BCL11A-6147	+	CUAAACAGGGGGGGAGUGGG	20	7739
  BCL11A-6148	+	CUGGGUACUACGCCGAAUGG	20	7740
  BCL11A-6149	+	UCUCCUAGAGAAAUCCAUGG	20	7741
  BCL11A-6150	+	GUCGGACUUGACCGUCAUGG	20	7742
  BCL11A-6151	-	CAAAUUUCAGAGCAACCUGG	20	7743
  BCL11A-6152	+	GCUUCUCGCCCAGGACCUGG	20	7744
  BCL11A-6153	-	CGGCUUCGGGCUGAGCCUGG	20	7745
  BCL11A-6154	-	CCACCGCAUAGAGCGCCUGG	20	7746
  BCL11A-6155	+	GGGAUCUUUGAGCUGCCUGG	20	7747
  BCL11A-6156	+	GCCGGGUUCCGGGGAGCUGG	20	7748
  BCL11A-6157	-	CGCAGCGGCACGGGAAGUGG	20	7749
  BCL11A-6158	-	CAGCGCGCUCAAGUCCGUGG	20	7750
  BCL11A-6159	+	CCCGCGAGCUGUUCUCGUGG	20	7751
  BCL11A-6160	+	CCAGGCGCUCUAUGCGGUGG	20	7752
  BCL11A-6161	+	UCCAAGUGAUGUCUCGGUGG	20	7753
  BCL11A-6162	-	ACCCGGCACCAGCGACUUGG	20	7754
  BCL11A-6163	+	UCUGGGUACUACGCCGAAUG	20	7755
  BCL11A-6164	+	CGUCGGACUUGACCGUCAUG	20	7756
  BCL11A-6165	+	UGUGCAUGUGCGUCUUCAUG	20	7757
  BCL11A-6166	+	GGGCCCGGACCACUAAUAUG	20	7758
  BCL11A-6167	+	CCGCCCCCAGGCGCUCUAUG	20	7759
  BCL11A-6168	+	UAACAGUGCCAUCGUCUAUG	20	7760
  BCL11A-6169	-	AGCGACACUUGUGAGUACUG	20	7761
  BCL11A-6170	+	CUUCGUCGCAAGUGUCCCUG	20	7762
  BCL11A-6171	-	CCCACCGCAUAGAGCGCCUG	20	7763
  BCL11A-6172	+	CAUAGGGCUGGGCCGGCCUG	20	7764
  BCL11A-6173	+	AGAAGGGGCUCAGCGAGCUG	20	7765
  BCL11A-6174	-	GUGCCUUUGACAGGGUGCUG	20	7766
  BCL11A-6175	-	UCCAAGUCAUGCGAGUUCUG	20	7767
  BCL11A-6176	+	UGUAGGGCUUCUCGCCCGUG	20	7768
  BCL11A-6177	+	GUCCAGCUCCCCGGGCGGUG	20	7769
  BCL11A-6178	+	CCCAGGCGCUCUAUGCGGUG	20	7770
  BCL11A-6179	-	AUUUGAAGCCCCCAGGGGUG	20	7771
  BCL11A-6180	-	CCCAGAGAGCUCAAGAUGUG	20	7772
  BCL11A-6181	+	CGUUCUCCGGGAUCAGGUUG	20	7773
  BCL11A-6182	+	CUCUGGGUACUACGCCGAAU	20	7774
  BCL11A-6183	+	GCGGGAGGCUCCAUAGCCAU	20	7775
  BCL11A-6184	-	CUUCCCAGCCACCUCUCCAU	20	7776
  BCL11A-6185	+	GGUUGCAGUAACCUUUGCAU	20	7777
  BCL11A-6186	+	UCGUCGGACUUGACCGUCAU	20	7778
  BCL11A-6187	+	GUCAAAGGCACUCGGGUGAU	20	7779
  BCL11A-6188	+	CGGGCCCGGACCACUAAUAU	20	7780
  BCL11A-6189	+	GUCGUUCUCGCUCUUGAACU	20	7781
  BCL11A-6190	+	AGCACCCUGUCAAAGGCACU	20	7782
  BCL11A-6191	-	UCCACCACCGAGACAUCACU	20	7783
  BCL11A-6192	-	GGACACUUGCGACGAAGACU	20	7784
  BCL11A-6193	-	GGAACCCGGCACCAGCGACU	20	7785
  BCL11A-6194	-	GUUGGUAUCCCUUCAGGACU	20	7786
  BCL11A-6195	+	GCCGCAGAACUCGCAUGACU	20	7787
  BCL11A-6196	+	GCAAGUGUCCCUGUGGCCCU	20	7788
  BCL11A-6197	-	CCCCACCGCAUAGAGCGCCU	20	7789
  BCL11A-6198	+	GCAUAGGGCUGGGCCGGCCU	20	7790
  BCL11A-6199	+	GUCCCUGUGGCCCUCGGCCU	20	7791
  BCL11A-6200	-	CUCCCCGGGCGAGUCGGCCU	20	7792
  BCL11A-6201	+	GCGCUUCAGCUUGCUGGCCU	20	7793
  BCL11A-6202	-	CUCCUCGUCGGAGCACUCCU	20	7794
  BCL11A-6203	-	GAGGCCUUCCACCAGGUCCU	20	7795
  BCL11A-6204	+	GAGAAGGGGCUCAGCGAGCU	20	7796
  BCL11A-6205	+	CGUCUGCCCUCUUUUGAGCU	20	7797
  BCL11A-6206	+	AGUAACCUUUGCAUAGGGCU	20	7798
  BCL11A-6207	+	CUUGGACUUGACCGGGGGCU	20	7799
  BCL11A-6208	+	AAUCCCAUGGAGAGGUGGCU	20	7800
  BCL11A-5508	+	GUUGUACAUGUGUAGCUGCU	20	7801
  BCL11A-6209	-	CUGUCCAAAAAGCUGCUGCU	20	7802
  BCL11A-6210	-	GGAGCUGGACGGAGGGAUCU	20	7803
  BCL11A-6211	+	CCACACAUCUUGAGCUCUCU	20	7804
  BCL11A-6212	-	CUCCCGCCAUGGAUUUCUCU	20	7805
  BCL11A-6213	+	UGGGGGUCCAAGUGAUGUCU	20	7806
  BCL11A-6214	-	UCUGUCUCCAACCUCUUUCU	20	7807
  BCL11A-6215	-	AGACUCGGUGGCCGGCGAGU	20	7808
  BCL11A-6216	-	CGGCUGCUCCCCGGGCGAGU	20	7809
  BCL11A-6217	+	GGACUAAACAGGGGGGGAGU	20	7810
  BCL11A-6218	+	CACCAUGCCCUGCAUGACGU	20	7811
  BCL11A-6219	-	CGGGGCGCGGUCGUGGGCGU	20	7812
  BCL11A-6220	-	AUCGCCUUUUGCCUCCUCGU	20	7813
  BCL11A-6221	+	GGCGGUGGAGAGACCGUCGU	20	7814
  BCL11A-6222	-	AGCUCGCGGGGCGCGGUCGU	20	7815
  BCL11A-6223	+	CCCGUUCUCCGGGAUCAGGU	20	7816
  BCL11A-6224	+	UGAAGAACCUAGAAAGAGGU	20	7817
  BCL11A-6225	+	GCCGGCCUGGGGACAGCGGU	20	7818
  BCL11A-6226	+	CCCCAGGCGCUCUAUGCGGU	20	7819
  BCL11A-6227	-	AGUCCCCUGACCCCGCGGGU	20	7820
  BCL11A-6228	-	AAUUUGAAGCCCCCAGGGGU	20	7821
  BCL11A-6229	-	CCCGGCACCAGCGACUUGGU	20	7822
  BCL11A-6230	-	GCGACACUUGUGAGUACUGU	20	7823
  BCL11A-6231	+	CGAGUACACGUUCUCCGUGU	20	7824
  BCL11A-6232	+	GUCGCACAGGUUGCACUUGU	20	7825
  BCL11A-6233	-	GUUCUUCACACACCCCCAUU	20	7826
  BCL11A-6234	-	AAAGAUCCCUUCCUUAGCUU	20	7827
  BCL11A-6235	-	GAGAGGGUGGACUACGGCUU	20	7828
  BCL11A-6236	+	CCGUUCUCCGGGAUCAGGUU	20	7829
  BCL11A-6237	+	GAGUACACGUUCUCCGUGUU	20	7830
  BCL11A-6238	+	GCUGCCCAGCAGCAGCUUUU	20	7831
  BCL11A-6239	-	UCAAGAUGUGUGGCAGUUUU	20	7832

• Table 15D provides targeting domains for knocking out the BCL11A 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 0-50 bp. 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. Exemplary gRNA pairs to be used with S. pyogenes Cas9 are shown in Table 151D, e.g., BCL11A-5355 or BCL11A-5380 can be combined with BCL11A-5321 or BCL11A-5416; or BCL11A-5333, BCL11A-5354, or BCL11A-5329 can be combined with BCL11A-5367 or BCL11A-5341.

• 	TABLE 15D
  	Group A	Group B
  	BCL11A-5355,	BCL11A-5321,
  	BCL11A-5380	BCL11A-5416
  	Group C	Group D
  	BCL11A-5333, BCL11A-	BCL11A-5367,
  	5354, BCL11A-5329	BCL11A-5341

• Table 16A 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, 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 16A
  1st Tier

  	DNA		Target Site	SEQ ID
  gRNA Name	Strand	Targeting Domain	Length	NO:
  BCL11A-6240	+	UGACCUGGAUGCCAACCUCCA	21	7833
  BCL11A-6241	+	GUGACCUGGAUGCCAACCUCCA	22	7834
  BCL11A-6242	+	CGUGACCUGGAUGCCAACCUCCA	23	7835
  BCL11A-6243	+	GCGUGACCUGGAUGCCAACCUCCA	24	7836
  BCL11A-6244	+	AUGCCAACCUCCACGGGA	18	7837
  BCL11A-6245	+	GAUGCCAACCUCCACGGGA	19	7838
  BCL11A-6246	+	GGAUGCCAACCUCCACGGGA	20	7839
  BCL11A-6247	+	UGGAUGCCAACCUCCACGGGA	21	7840
  BCL11A-6248	+	CUGGAUGCCAACCUCCACGGGA	22	7841
  BCL11A-6249	+	CCUGGAUGCCAACCUCCACGGGA	23	7842
  BCL11A-6250	+	ACCUGGAUGCCAACCUCCACGGGA	24	7843
  BCL11A-6251	+	GUCAUCCUCUGGCGUGAC	18	7844
  BCL11A-6252	+	CGUCAUCCUCUGGCGUGAC	19	7845
  BCL11A-6253	+	UCGUCAUCCUCUGGCGUGAC	20	7846
  BCL11A-6254	+	AUCGUCAUCCUCUGGCGUGAC	21	7847
  BCL11A-6255	+	AAUCGUCAUCCUCUGGCGUGAC	22	7848
  BCL11A-6256	+	CAAUCGUCAUCCUCUGGCGUGAC	23	7849
  BCL11A-6257	+	ACAAUCGUCAUCCUCUGGCGUGAC	24	7850
  BCL11A-6258	+	UUAUUGGGUUACUUACGC	18	7851
  BCL11A-6259	+	AUUAUUGGGUUACUUACGC	19	7852
  BCL11A-6260	+	UAUUAUUGGGUUACUUACGC	20	7853
  BCL11A-6261	+	CUAUUAUUGGGUUACUUACGC	21	7854
  BCL11A-6262	+	ACUAUUAUUGGGUUACUUACGC	22	7855
  BCL11A-6263	+	UACUAUUAUUGGGUUACUUACGC	23	7856
  BCL11A-6264	+	UUACUAUUAUUGGGUUACUUACGC	24	7857
  BCL11A-6265	+	UCCCGUUUGCUUAAGUGC	18	7858
  BCL11A-6266	+	UUCCCGUUUGCUUAAGUGC	19	7859
  BCL11A-5352	+	AUUCCCGUUUGCUUAAGUGC	20	7860
  BCL11A-6267	+	AAUUCCCGUUUGCUUAAGUGC	21	7861
  BCL11A-6268	+	GAAUUCCCGUUUGCUUAAGUGC	22	7862
  BCL11A-6269	+	AGAAUUCCCGUUUGCUUAAGUGC	23	7863
  BCL11A-6270	+	GAGAAUUCCCGUUUGCUUAAGUGC	24	7864
  BCL11A-6271	+	UUUGUGCUCGAUAAAAAU	18	7865
  BCL11A-6272	+	GUUUGUGCUCGAUAAAAAU	19	7866
  BCL11A-6273	+	CGUUUGUGCUCGAUAAAAAU	20	7867
  BCL11A-6274	+	CCGUUUGUGCUCGAUAAAAAU	21	7868
  BCL11A-6275	+	UCCGUUUGUGCUCGAUAAAAAU	22	7869
  BCL11A-6276	+	UUCCGUUUGUGCUCGAUAAAAAU	23	7870
  BCL11A-6277	+	UUUCCGUUUGUGCUCGAUAAAAAU	24	7871
  BCL11A-6278	+	UGCACUCAUCCCAGGCGU	18	7872
  BCL11A-6279	+	CUGCACUCAUCCCAGGCGU	19	7873
  BCL11A-5510	+	UCUGCACUCAUCCCAGGCGU	20	7874
  BCL11A-6280	+	UUCUGCACUCAUCCCAGGCGU	21	7875
  BCL11A-6281	+	AUUCUGCACUCAUCCCAGGCGU	22	7876
  BCL11A-6282	+	UAUUCUGCACUCAUCCCAGGCGU	23	7877
  BCL11A-6283	+	AUAUUCUGCACUCAUCCCAGGCGU	24	7878
  BCL11A-6284	+	GUCUGGUUCAUCAUCUGU	18	7879
  BCL11A-6285	+	GGUCUGGUUCAUCAUCUGU	19	7880
  BCL11A-6286	+	UGGUCUGGUUCAUCAUCUGU	20	7881
  BCL11A-6287	+	GUGGUCUGGUUCAUCAUCUGU	21	7882
  BCL11A-6288	+	CGUGGUCUGGUUCAUCAUCUGU	22	7883
  BCL11A-6289	+	CCGUGGUCUGGUUCAUCAUCUGU	23	7884
  BCL11A-6290	+	GCCGUGGUCUGGUUCAUCAUCUGU	24	7885
  BCL11A-6291	-	CCGUUGGGAGCUCCAGAA	18	7886
  BCL11A-6292	-	CCCGUUGGGAGCUCCAGAA	19	7887
  BCL11A-5447	-	GCCCGUUGGGAGCUCCAGAA	20	7888
  BCL11A-6293	-	GGCCCGUUGGGAGCUCCAGAA	21	7889
  BCL11A-6294	-	CGGCCCGUUGGGAGCUCCAGAA	22	7890
  BCL11A-6295	-	ACGGCCCGUUGGGAGCUCCAGAA	23	7891
  BCL11A-6296	-	CACGGCCCGUUGGGAGCUCCAGAA	24	7892
  BCL11A-6297	-	GGCAUCCAGGUCACGCCA	18	7893
  BCL11A-6298	-	UGGCAUCCAGGUCACGCCA	19	7894
  BCL11A-6299	-	UUGGCAUCCAGGUCACGCCA	20	7895
  BCL11A-6300	-	GUUGGCAUCCAGGUCACGCCA	21	7896
  BCL11A-6301	-	GGUUGGCAUCCAGGUCACGCCA	22	7897
  BCL11A-6302	-	AGGUUGGCAUCCAGGUCACGCCA	23	7898
  BCL11A-6303	-	GAGGUUGGCAUCCAGGUCACGCCA	24	7899
  BCL11A-6304	-	AACCCCAGCACUUAAGCAAAC	21	7900
  BCL11A-6305	-	AAACCCCAGCACUUAAGCAAAC	22	7901
  BCL11A-6306	-	CAAACCCCAGCACUUAAGCAAAC	23	7902
  BCL11A-6307	-	GCAAACCCCAGCACUUAAGCAAAC	24	7903
  BCL11A-6308	-	AGCUCUAAUCCCCACGCC	18	7904
  BCL11A-6309	-	GAGCUCUAAUCCCCACGCC	19	7905
  BCL11A-5350	-	GGAGCUCUAAUCCCCACGCC	20	7906
  BCL11A-6310	-	UGGAGCUCUAAUCCCCACGCC	21	7907
  BCL11A-6311	-	AUGGAGCUCUAAUCCCCACGCC	22	7908
  BCL11A-6312	-	CAUGGAGCUCUAAUCCCCACGCC	23	7909
  BCL11A-6313	-	ACAUGGAGCUCUAAUCCCCACGCC	24	7910
  BCL11A-6314	-	UUUAUCAACGUCAUCUAG	18	7911
  BCL11A-6315	-	GUUUAUCAACGUCAUCUAG	19	7912
  BCL11A-5356	-	UGUUUAUCAACGUCAUCUAG	20	7913
  BCL11A-6316	-	UUGUUUAUCAACGUCAUCUAG	21	7914
  BCL11A-6317	-	AUUGUUUAUCAACGUCAUCUAG	22	7915
  BCL11A-6318	-	GAUUGUUUAUCAACGUCAUCUAG	23	7916
  BCL11A-6319	-	CGAUUGUUUAUCAACGUCAUCUAG	24	7917
  BCL11A-6320	-	AGUGCAGAAUAUGCCCCG	18	7918
  BCL11A-6321	-	GAGUGCAGAAUAUGCCCCG	19	7919
  BCL11A-6322	-	UGAGUGCAGAAUAUGCCCCG	20	7920
  BCL11A-6323	-	AUGAGUGCAGAAUAUGCCCCG	21	7921
  BCL11A-6324	-	GAUGAGUGCAGAAUAUGCCCCG	22	7922
  BCL11A-6325	-	GGAUGAGUGCAGAAUAUGCCCCG	23	7923
  BCL11A-6326	-	GGGAUGAGUGCAGAAUAUGCCCCG	24	7924
  BCL11A-6327	-	CUAAUCCCCACGCCUGGG	18	7925
  BCL11A-6328	-	UCUAAUCCCCACGCCUGGG	19	7926
  BCL11A-6329	-	CUCUAAUCCCCACGCCUGGG	20	7927
  BCL11A-6330	-	GCUCUAAUCCCCACGCCUGGG	21	7928
  BCL11A-6331	-	AGCUCUAAUCCCCACGCCUGGG	22	7929
  BCL11A-6332	-	GAGCUCUAAUCCCCACGCCUGGG	23	7930
  BCL11A-6333	-	GGAGCUCUAAUCCCCACGCCUGGG	24	7931
  BCL11A-6334	-	CCACGCCUGGGAUGAGUG	18	7932
  BCL11A-6335	-	CCCACGCCUGGGAUGAGUG	19	7933
  BCL11A-6336	-	CCCCACGCCUGGGAUGAGUG	20	7934
  BCL11A-6337	-	UCCCCACGCCUGGGAUGAGUG	21	7935
  BCL11A-6338	-	AUCCCCACGCCUGGGAUGAGUG	22	7936
  BCL11A-6339	-	AAUCCCCACGCCUGGGAUGAGUG	23	7937
  BCL11A-6340	-	UAAUCCCCACGCCUGGGAUGAGUG	24	7938
  BCL11A-6341	-	CUCUGCUUAGAAAAAGCU	18	7939
  BCL11A-6342	-	CCUCUGCUUAGAAAAAGCU	19	7940
  BCL11A-6343	-	GCCUCUGCUUAGAAAAAGCU	20	7941
  BCL11A-6344	-	AGCCUCUGCUUAGAAAAAGCU	21	7942
  BCL11A-6345	-	CAGCCUCUGCUUAGAAAAAGCU	22	7943
  BCL11A-6346	-	GCAGCCUCUGCUUAGAAAAAGCU	23	7944
  BCL11A-6347	-	GGCAGCCUCUGCUUAGAAAAAGCU	24	7945

• Table 16B 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 16B
  2nd Tier

  	DNA		Target Site	SEQ ID
  gRNA Name	Strand	Targeting Domain	Length	NO:
  BCL11A-6348	+	CCUGGAUGCCAACCUCCA	18	7946
  BCL11A-6349	+	ACCUGGAUGCCAACCUCCA	19	7947
  BCL11A-5450	+	GACCUGGAUGCCAACCUCCA	20	7948
  BCL11A-6350	-	CCCAGCACUUAAGCAAAC	18	7949
  BCL11A-6351	-	CCCCAGCACUUAAGCAAAC	19	7950
  BCL11A-5458	-	ACCCCAGCACUUAAGCAAAC	20	7951

• Table 16C 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 16C
  3rd Tier

  	DNA		Target Site	SEQ ID
  gRNA Name	Strand	Targeting Domain	Length	NO:
  BCL11A-6352	+	AAUAAGAAUGUCCCCCAA	18	7952
  BCL11A-6353	+	AAAUAAGAAUGUCCCCCAA	19	7953
  BCL11A-5444	+	AAAAUAAGAAUGUCCCCCAA	20	7954
  BCL11A-6354	+	AAAAAUAAGAAUGUCCCCCAA	21	7955
  BCL11A-6355	+	UAAAAAUAAGAAUGUCCCCCAA	22	7956
  BCL11A-6356	+	AUAAAAAUAAGAAUGUCCCCCAA	23	7957
  BCL11A-6357	+	GAUAAAAAUAAGAAUGUCCCCCAA	24	7958
  BCL11A-6358	+	UUCAUCUCGAUUGGUGAA	18	7959
  BCL11A-6359	+	UUUCAUCUCGAUUGGUGAA	19	7960
  BCL11A-5344	+	UUUUCAUCUCGAUUGGUGAA	20	7961
  BCL11A-6360	+	UUUUUCAUCUCGAUUGGUGAA	21	7962
  BCL11A-6361	+	UUUUUUCAUCUCGAUUGGUGAA	22	7963
  BCL11A-6362	+	CUUUUUUCAUCUCGAUUGGUGAA	23	7964
  BCL11A-6363	+	GCUUUUUUCAUCUCGAUUGGUGAA	24	7965
  BCL11A-6364	+	AAAUAAGAAUGUCCCCCA	18	7966
  BCL11A-6365	+	AAAAUAAGAAUGUCCCCCA	19	7967
  BCL11A-6366	+	AAAAAUAAGAAUGUCCCCCA	20	7968
  BCL11A-6367	+	UAAAAAUAAGAAUGUCCCCCA	21	7969
  BCL11A-6368	+	AUAAAAAUAAGAAUGUCCCCCA	22	7970
  BCL11A-6369	+	GAUAAAAAUAAGAAUGUCCCCCA	23	7971
  BCL11A-6370	+	CGAUAAAAAUAAGAAUGUCCCCCA	24	7972
  BCL11A-6371	+	CCCCUUCUGGAGCUCCCA	18	7973
  BCL11A-6372	+	UCCCCUUCUGGAGCUCCCA	19	7974
  BCL11A-6373	+	AUCCCCUUCUGGAGCUCCCA	20	7975
  BCL11A-6374	+	GAUCCCCUUCUGGAGCUCCCA	21	7976
  BCL11A-6375	+	UGAUCCCCUUCUGGAGCUCCCA	22	7977
  BCL11A-6376	+	AUGAUCCCCUUCUGGAGCUCCCA	23	7978
  BCL11A-6377	+	CAUGAUCCCCUUCUGGAGCUCCCA	24	7979
  BCL11A-6378	+	UAGAGCUCCAUGUGCAGA	18	7980
  BCL11A-6379	+	UUAGAGCUCCAUGUGCAGA	19	7981
  BCL11A-6380	+	AUUAGAGCUCCAUGUGCAGA	20	7982
  BCL11A-6381	+	GAUUAGAGCUCCAUGUGCAGA	21	7983
  BCL11A-6382	+	GGAUUAGAGCUCCAUGUGCAGA	22	7984
  BCL11A-6383	+	GGGAUUAGAGCUCCAUGUGCAGA	23	7985
  BCL11A-6384	+	GGGGAUUAGAGCUCCAUGUGCAGA	24	7986
  BCL11A-6385	+	GCUCCAUGUGCAGAACGA	18	7987
  BCL11A-6386	+	AGCUCCAUGUGCAGAACGA	19	7988
  BCL11A-5347	+	GAGCUCCAUGUGCAGAACGA	20	7989
  BCL11A-6387	+	AGAGCUCCAUGUGCAGAACGA	21	7990
  BCL11A-6388	+	UAGAGCUCCAUGUGCAGAACGA	22	7991
  BCL11A-6389	+	UUAGAGCUCCAUGUGCAGAACGA	23	7992
  BCL11A-6390	+	AUUAGAGCUCCAUGUGCAGAACGA	24	7993
  BCL11A-6391	+	UUUCAUCUCGAUUGGUGA	18	7994
  BCL11A-6392	+	UUUUCAUCUCGAUUGGUGA	19	7995
  BCL11A-5456	+	UUUUUCAUCUCGAUUGGUGA	20	7996
  BCL11A-6393	+	UUUUUUCAUCUCGAUUGGUGA	21	7997
  BCL11A-6394	+	CUUUUUUCAUCUCGAUUGGUGA	22	7998
  BCL11A-6395	+	GCUUUUUUCAUCUCGAUUGGUGA	23	7999
  BCL11A-6396	+	UGCUUUUUUCAUCUCGAUUGGUGA	24	8000
  BCL11A-6397	+	GCAGAAGUUUAUCUGUGA	18	8001
  BCL11A-6398	+	UGCAGAAGUUUAUCUGUGA	19	8002
  BCL11A-6399	+	GUGCAGAAGUUUAUCUGUGA	20	8003
  BCL11A-6400	+	AGUGCAGAAGUUUAUCUGUGA	21	8004
  BCL11A-6401	+	CAGUGCAGAAGUUUAUCUGUGA	22	8005
  BCL11A-6402	+	CCAGUGCAGAAGUUUAUCUGUGA	23	8006
  BCL11A-6403	+	UCCAGUGCAGAAGUUUAUCUGUGA	24	8007
  BCL11A-6404	+	GAGCUCCAUGUGCAGAAC	18	8008
  BCL11A-6405	+	AGAGCUCCAUGUGCAGAAC	19	8009
  BCL11A-6406	+	UAGAGCUCCAUGUGCAGAAC	20	8010
  BCL11A-6407	+	UUAGAGCUCCAUGUGCAGAAC	21	8011
  BCL11A-6408	+	AUUAGAGCUCCAUGUGCAGAAC	22	8012
  BCL11A-6409	+	GAUUAGAGCUCCAUGUGCAGAAC	23	8013
  BCL11A-6410	+	GGAUUAGAGCUCCAUGUGCAGAAC	24	8014
  BCL11A-6411	+	UAUUAUUGGGUUACUUAC	18	8015
  BCL11A-6412	+	CUAUUAUUGGGUUACUUAC	19	8016
  BCL11A-6413	+	ACUAUUAUUGGGUUACUUAC	20	8017
  BCL11A-6414	+	UACUAUUAUUGGGUUACUUAC	21	8018
  BCL11A-6415	+	UUACUAUUAUUGGGUUACUUAC	22	8019
  BCL11A-6416	+	AUUACUAUUAUUGGGUUACUUAC	23	8020
  BCL11A-6417	+	UAUUACUAUUAUUGGGUUACUUAC	24	8021
  BCL11A-6418	+	ACCUGGAUGCCAACCUCC	18	8022
  BCL11A-6419	+	GACCUGGAUGCCAACCUCC	19	8023
  BCL11A-6420	+	UGACCUGGAUGCCAACCUCC	20	8024
  BCL11A-6421	+	GUGACCUGGAUGCCAACCUCC	21	8025
  BCL11A-6422	+	CGUGACCUGGAUGCCAACCUCC	22	8026
  BCL11A-6423	+	GCGUGACCUGGAUGCCAACCUCC	23	8027
  BCL11A-6424	+	GGCGUGACCUGGAUGCCAACCUCC	24	8028
  BCL11A-6425	+	UCUGCACUCAUCCCAGGC	18	8029
  BCL11A-6426	+	UUCUGCACUCAUCCCAGGC	19	8030
  BCL11A-6427	+	AUUCUGCACUCAUCCCAGGC	20	8031
  BCL11A-6428	+	UAUUCUGCACUCAUCCCAGGC	21	8032
  BCL11A-6429	+	AUAUUCUGCACUCAUCCCAGGC	22	8033
  BCL11A-6430	+	CAUAUUCUGCACUCAUCCCAGGC	23	8034
  BCL11A-6431	+	GCAUAUUCUGCACUCAUCCCAGGC	24	8035
  BCL11A-6432	+	GAGGUCAUGAUCCCCUUC	18	8036
  BCL11A-6433	+	GGAGGUCAUGAUCCCCUUC	19	8037
  BCL11A-5471	+	AGGAGGUCAUGAUCCCCUUC	20	8038
  BCL11A-6434	+	GAGGAGGUCAUGAUCCCCUUC	21	8039
  BCL11A-6435	+	UGAGGAGGUCAUGAUCCCCUUC	22	8040
  BCL11A-6436	+	GUGAGGAGGUCAUGAUCCCCUUC	23	8041
  BCL11A-6437	+	GGUGAGGAGGUCAUGAUCCCCUUC	24	8042
  BCL11A-6438	+	AUCUGUAAGAAUGGCUUC	18	8043
  BCL11A-6439	+	CAUCUGUAAGAAUGGCUUC	19	8044
  BCL11A-6440	+	UCAUCUGUAAGAAUGGCUUC	20	8045
  BCL11A-6441	+	AUCAUCUGUAAGAAUGGCUUC	21	8046
  BCL11A-6442	+	CAUCAUCUGUAAGAAUGGCUUC	22	8047
  BCL11A-6443	+	UCAUCAUCUGUAAGAAUGGCUUC	23	8048
  BCL11A-6444	+	UUCAUCAUCUGUAAGAAUGGCUUC	24	8049
  BCL11A-6445	+	UCAUCUCGAUUGGUGAAG	18	8050
  BCL11A-6446	+	UUCAUCUCGAUUGGUGAAG	19	8051
  BCL11A-5355	+	UUUCAUCUCGAUUGGUGAAG	20	8052
  BCL11A-6447	+	UUUUCAUCUCGAUUGGUGAAG	21	8053
  BCL11A-6448	+	UUUUUCAUCUCGAUUGGUGAAG	22	8054
  BCL11A-6449	+	UUUUUUCAUCUCGAUUGGUGAAG	23	8055
  BCL11A-6450	+	CUUUUUUCAUCUCGAUUGGUGAAG	24	8056
  BCL11A-6451	+	UCCACAGCUUUUUCUAAG	18	8057
  BCL11A-6452	+	AUCCACAGCUUUUUCUAAG	19	8058
  BCL11A-6453	+	UAUCCACAGCUUUUUCUAAG	20	8059
  BCL11A-6454	+	UUAUCCACAGCUUUUUCUAAG	21	8060
  BCL11A-6455	+	CUUAUCCACAGCUUUUUCUAAG	22	8061
  BCL11A-6456	+	GCUUAUCCACAGCUUUUUCUAAG	23	8062
  BCL11A-6457	+	GGCUUAUCCACAGCUUUUUCUAAG	24	8063
  BCL11A-6458	+	AUCUGGCACUGCCCACAG	18	8064
  BCL11A-6459	+	CAUCUGGCACUGCCCACAG	19	8065
  BCL11A-6460	+	UCAUCUGGCACUGCCCACAG	20	8066
  BCL11A-6461	+	UUCAUCUGGCACUGCCCACAG	21	8067
  BCL11A-6462	+	GUUCAUCUGGCACUGCCCACAG	22	8068
  BCL11A-6463	+	AGUUCAUCUGGCACUGCCCACAG	23	8069
  BCL11A-6464	+	AAGUUCAUCUGGCACUGCCCACAG	24	8070
  BCL11A-6465	+	CUCCAUGUGCAGAACGAG	18	8071
  BCL11A-6466	+	GCUCCAUGUGCAGAACGAG	19	8072
  BCL11A-5476	+	AGCUCCAUGUGCAGAACGAG	20	8073
  BCL11A-6467	+	GAGCUCCAUGUGCAGAACGAG	21	8074
  BCL11A-6468	+	AGAGCUCCAUGUGCAGAACGAG	22	8075
  BCL11A-6469	+	UAGAGCUCCAUGUGCAGAACGAG	23	8076
  BCL11A-6470	+	UUAGAGCUCCAUGUGCAGAACGAG	24	8077
  BCL11A-6471	+	UGUGCAGAACGAGGGGAG	18	8078
  BCL11A-6472	+	AUGUGCAGAACGAGGGGAG	19	8079
  BCL11A-6473	+	CAUGUGCAGAACGAGGGGAG	20	8080
  BCL11A-6474	+	CCAUGUGCAGAACGAGGGGAG	21	8081
  BCL11A-6475	+	UCCAUGUGCAGAACGAGGGGAG	22	8082
  BCL11A-6476	+	CUCCAUGUGCAGAACGAGGGGAG	23	8083
  BCL11A-6477	+	GCUCCAUGUGCAGAACGAGGGGAG	24	8084
  BCL11A-6478	+	AGCUCCAUGUGCAGAACG	18	8085
  BCL11A-6479	+	GAGCUCCAUGUGCAGAACG	19	8086
  BCL11A-5357	+	AGAGCUCCAUGUGCAGAACG	20	8087
  BCL11A-6480	+	UAGAGCUCCAUGUGCAGAACG	21	8088
  BCL11A-6481	+	UUAGAGCUCCAUGUGCAGAACG	22	8089
  BCL11A-6482	+	AUUAGAGCUCCAUGUGCAGAACG	23	8090
  BCL11A-6483	+	GAUUAGAGCUCCAUGUGCAGAACG	24	8091
  BCL11A-6484	+	CUGCACUCAUCCCAGGCG	18	8092
  BCL11A-6485	+	UCUGCACUCAUCCCAGGCG	19	8093
  BCL11A-5480	+	UUCUGCACUCAUCCCAGGCG	20	8094
  BCL11A-6486	+	AUUCUGCACUCAUCCCAGGCG	21	8095
  BCL11A-6487	+	UAUUCUGCACUCAUCCCAGGCG	22	8096
  BCL11A-6488	+	AUAUUCUGCACUCAUCCCAGGCG	23	8097
  BCL11A-6489	+	CAUAUUCUGCACUCAUCCCAGGCG	24	8098
  BCL11A-6490	+	GGGUUUGCCUUGCUUGCG	18	8099
  BCL11A-6491	+	GGGGUUUGCCUUGCUUGCG	19	8100
  BCL11A-6492	+	UGGGGUUUGCCUUGCUUGCG	20	8101
  BCL11A-6493	+	CUGGGGUUUGCCUUGCUUGCG	21	8102
  BCL11A-6494	+	GCUGGGGUUUGCCUUGCUUGCG	22	8103
  BCL11A-6495	+	UGCUGGGGUUUGCCUUGCUUGCG	23	8104
  BCL11A-6496	+	GUGCUGGGGUUUGCCUUGCUUGCG	24	8105
  BCL11A-6497	+	CCAUGUGCAGAACGAGGG	18	8106
  BCL11A-6498	+	UCCAUGUGCAGAACGAGGG	19	8107
  BCL11A-6499	+	CUCCAUGUGCAGAACGAGGG	20	8108
  BCL11A-6500	+	GCUCCAUGUGCAGAACGAGGG	21	8109
  BCL11A-6501	+	AGCUCCAUGUGCAGAACGAGGG	22	8110
  BCL11A-6502	+	GAGCUCCAUGUGCAGAACGAGGG	23	8111
  BCL11A-6503	+	AGAGCUCCAUGUGCAGAACGAGGG	24	8112
  BCL11A-6504	+	GACAUGGUGGGCUGCGGG	18	8113
  BCL11A-6505	+	AGACAUGGUGGGCUGCGGG	19	8114
  BCL11A-6506	+	GAGACAUGGUGGGCUGCGGG	20	8115
  BCL11A-6507	+	CGAGACAUGGUGGGCUGCGGG	21	8116
  BCL11A-6508	+	GCGAGACAUGGUGGGCUGCGGG	22	8117
  BCL11A-6509	+	GGCGAGACAUGGUGGGCUGCGGG	23	8118
  BCL11A-6510	+	CGGCGAGACAUGGUGGGCUGCGGG	24	8119
  BCL11A-6511	+	CAUGUGCAGAACGAGGGG	18	8120
  BCL11A-6512	+	CCAUGUGCAGAACGAGGGG	19	8121
  BCL11A-5488	+	UCCAUGUGCAGAACGAGGGG	20	8122
  BCL11A-6513	+	CUCCAUGUGCAGAACGAGGGG	21	8123
  BCL11A-6514	+	GCUCCAUGUGCAGAACGAGGGG	22	8124
  BCL11A-6515	+	AGCUCCAUGUGCAGAACGAGGGG	23	8125
  BCL11A-6516	+	GAGCUCCAUGUGCAGAACGAGGGG	24	8126
  BCL11A-6517	+	CAAGAGGCUCGGCUGUGG	18	8127
  BCL11A-6518	+	UCAAGAGGCUCGGCUGUGG	19	8128
  BCL11A-6519	+	UUCAAGAGGCUCGGCUGUGG	20	8129
  BCL11A-6520	+	CUUCAAGAGGCUCGGCUGUGG	21	8130
  BCL11A-6521	+	GCUUCAAGAGGCUCGGCUGUGG	22	8131
  BCL11A-6522	+	GGCUUCAAGAGGCUCGGCUGUGG	23	8132
  BCL11A-6523	+	UGGCUUCAAGAGGCUCGGCUGUGG	24	8133
  BCL11A-6524	+	UGCUUGCGGCGAGACAUG	18	8134
  BCL11A-6525	+	UUGCUUGCGGCGAGACAUG	19	8135
  BCL11A-6526	+	CUUGCUUGCGGCGAGACAUG	20	8136
  BCL11A-6527	+	CCUUGCUUGCGGCGAGACAUG	21	8137
  BCL11A-6528	+	GCCUUGCUUGCGGCGAGACAUG	22	8138
  BCL11A-6529	+	UGCCUUGCUUGCGGCGAGACAUG	23	8139
  BCL11A-6530	+	UUGCCUUGCUUGCGGCGAGACAUG	24	8140
  BCL11A-6531	+	CAACUUACAAAUACCCUG	18	8141
  BCL11A-6532	+	UCAACUUACAAAUACCCUG	19	8142
  BCL11A-5494	+	CUCAACUUACAAAUACCCUG	20	8143
  BCL11A-6533	+	GCUCAACUUACAAAUACCCUG	21	8144
  BCL11A-6534	+	GGCUCAACUUACAAAUACCCUG	22	8145
  BCL11A-6535	+	AGGCUCAACUUACAAAUACCCUG	23	8146
  BCL11A-6536	+	AAGGCUCAACUUACAAAUACCCUG	24	8147
  BCL11A-6537	+	GUUGUACAUGUGUAGCUG	18	8148
  BCL11A-6538	+	AGUUGUACAUGUGUAGCUG	19	8149
  BCL11A-6539	+	AAGUUGUACAUGUGUAGCUG	20	8150
  BCL11A-6540	+	CAAGUUGUACAUGUGUAGCUG	21	8151
  BCL11A-6541	+	GCAAGUUGUACAUGUGUAGCUG	22	8152
  BCL11A-6542	+	UGCAAGUUGUACAUGUGUAGCUG	23	8153
  BCL11A-6543	+	UUGCAAGUUGUACAUGUGUAGCUG	24	8154
  BCL11A-6544	+	GCGAGACAUGGUGGGCUG	18	8155
  BCL11A-6545	+	GGCGAGACAUGGUGGGCUG	19	8156
  BCL11A-5361	+	CGGCGAGACAUGGUGGGCUG	20	8157
  BCL11A-6546	+	GCGGCGAGACAUGGUGGGCUG	21	8158
  BCL11A-6547	+	UGCGGCGAGACAUGGUGGGCUG	22	8159
  BCL11A-6548	+	UUGCGGCGAGACAUGGUGGGCUG	23	8160
  BCL11A-6549	+	CUUGCGGCGAGACAUGGUGGGCUG	24	8161
  BCL11A-6550	+	UUCCCGUUUGCUUAAGUG	18	8162
  BCL11A-6551	+	AUUCCCGUUUGCUUAAGUG	19	8163
  BCL11A-6552	+	AAUUCCCGUUUGCUUAAGUG	20	8164
  BCL11A-6553	+	GAAUUCCCGUUUGCUUAAGUG	21	8165
  BCL11A-6554	+	AGAAUUCCCGUUUGCUUAAGUG	22	8166
  BCL11A-6555	+	GAGAAUUCCCGUUUGCUUAAGUG	23	8167
  BCL11A-6556	+	CGAGAAUUCCCGUUUGCUUAAGUG	24	8168
  BCL11A-6557	+	GGAGAGGCCCCUCCAGUG	18	8169
  BCL11A-6558	+	AGGAGAGGCCCCUCCAGUG	19	8170
  BCL11A-6559	+	GAGGAGAGGCCCCUCCAGUG	20	8171
  BCL11A-6560	+	GGAGGAGAGGCCCCUCCAGUG	21	8172
  BCL11A-6561	+	GGGAGGAGAGGCCCCUCCAGUG	22	8173
  BCL11A-6562	+	GGGGAGGAGAGGCCCCUCCAGUG	23	8174
  BCL11A-6563	+	AGGGGAGGAGAGGCCCCUCCAGUG	24	8175
  BCL11A-6564	+	UGGCACUGCCCACAGGUG	18	8176
  BCL11A-6565	+	CUGGCACUGCCCACAGGUG	19	8177
  BCL11A-5498	+	UCUGGCACUGCCCACAGGUG	20	8178
  BCL11A-6566	+	AUCUGGCACUGCCCACAGGUG	21	8179
  BCL11A-6567	+	CAUCUGGCACUGCCCACAGGUG	22	8180
  BCL11A-6568	+	UCAUCUGGCACUGCCCACAGGUG	23	8181
  BCL11A-6569	+	UUCAUCUGGCACUGCCCACAGGUG	24	8182
  BCL11A-6570	+	UUUUCAUCUCGAUUGGUG	18	8183
  BCL11A-6571	+	UUUUUCAUCUCGAUUGGUG	19	8184
  BCL11A-6572	+	UUUUUUCAUCUCGAUUGGUG	20	8185
  BCL11A-6573	+	CUUUUUUCAUCUCGAUUGGUG	21	8186
  BCL11A-6574	+	GCUUUUUUCAUCUCGAUUGGUG	22	8187
  BCL11A-6575	+	UGCUUUUUUCAUCUCGAUUGGUG	23	8188
  BCL11A-6576	+	AUGCUUUUUUCAUCUCGAUUGGUG	24	8189
  BCL11A-6577	+	GGAUUAGAGCUCCAUGUG	18	8190
  BCL11A-6578	+	GGGAUUAGAGCUCCAUGUG	19	8191
  BCL11A-6579	+	GGGGAUUAGAGCUCCAUGUG	20	8192
  BCL11A-6580	+	UGGGGAUUAGAGCUCCAUGUG	21	8193
  BCL11A-6581	+	GUGGGGAUUAGAGCUCCAUGUG	22	8194
  BCL11A-6582	+	CGUGGGGAUUAGAGCUCCAUGUG	23	8195
  BCL11A-6583	+	GCGUGGGGAUUAGAGCUCCAUGUG	24	8196
  BCL11A-6584	+	CUUUUUUCAUCUCGAUUG	18	8197
  BCL11A-6585	+	GCUUUUUUCAUCUCGAUUG	19	8198
  BCL11A-6586	+	UGCUUUUUUCAUCUCGAUUG	20	8199
  BCL11A-6587	+	AUGCUUUUUUCAUCUCGAUUG	21	8200
  BCL11A-6588	+	GAUGCUUUUUUCAUCUCGAUUG	22	8201
  BCL11A-6589	+	GGAUGCUUUUUUCAUCUCGAUUG	23	8202
  BCL11A-6590	+	UGGAUGCUUUUUUCAUCUCGAUUG	24	8203
  BCL11A-6591	+	GAGGCUCGGCUGUGGUUG	18	8204
  BCL11A-6592	+	AGAGGCUCGGCUGUGGUUG	19	8205
  BCL11A-6593	+	AAGAGGCUCGGCUGUGGUUG	20	8206
  BCL11A-6594	+	CAAGAGGCUCGGCUGUGGUUG	21	8207
  BCL11A-6595	+	UCAAGAGGCUCGGCUGUGGUUG	22	8208
  BCL11A-6596	+	UUCAAGAGGCUCGGCUGUGGUUG	23	8209
  BCL11A-6597	+	CUUCAAGAGGCUCGGCUGUGGUUG	24	8210
  BCL11A-6598	+	AUAAGAAUGUCCCCCAAU	18	8211
  BCL11A-6599	+	AAUAAGAAUGUCCCCCAAU	19	8212
  BCL11A-5502	+	AAAUAAGAAUGUCCCCCAAU	20	8213
  BCL11A-6600	+	AAAAUAAGAAUGUCCCCCAAU	21	8214
  BCL11A-6601	+	AAAAAUAAGAAUGUCCCCCAAU	22	8215
  BCL11A-6602	+	UAAAAAUAAGAAUGUCCCCCAAU	23	8216
  BCL11A-6603	+	AUAAAAAUAAGAAUGUCCCCCAAU	24	8217
  BCL11A-6604	+	CAUCCCAGGCGUGGGGAU	18	8218
  BCL11A-6605	+	UCAUCCCAGGCGUGGGGAU	19	8219
  BCL11A-6606	+	CUCAUCCCAGGCGUGGGGAU	20	8220
  BCL11A-6607	+	ACUCAUCCCAGGCGUGGGGAU	21	8221
  BCL11A-6608	+	CACUCAUCCCAGGCGUGGGGAU	22	8222
  BCL11A-6609	+	GCACUCAUCCCAGGCGUGGGGAU	23	8223
  BCL11A-6610	+	UGCACUCAUCCCAGGCGUGGGGAU	24	8224
  BCL11A-6611	+	UCAACUUACAAAUACCCU	18	8225
  BCL11A-6612	+	CUCAACUUACAAAUACCCU	19	8226
  BCL11A-6613	+	GCUCAACUUACAAAUACCCU	20	8227
  BCL11A-6614	+	GGCUCAACUUACAAAUACCCU	21	8228
  BCL11A-6615	+	AGGCUCAACUUACAAAUACCCU	22	8229
  BCL11A-6616	+	AAGGCUCAACUUACAAAUACCCU	23	8230
  BCL11A-6617	+	UAAGGCUCAACUUACAAAUACCCU	24	8231
  BCL11A-6618	+	GGCGAGACAUGGUGGGCU	18	8232
  BCL11A-6619	+	CGGCGAGACAUGGUGGGCU	19	8233
  BCL11A-6620	+	GCGGCGAGACAUGGUGGGCU	20	8234
  BCL11A-6621	+	UGCGGCGAGACAUGGUGGGCU	21	8235
  BCL11A-6622	+	UUGCGGCGAGACAUGGUGGGCU	22	8236
  BCL11A-6623	+	CUUGCGGCGAGACAUGGUGGGCU	23	8237
  BCL11A-6624	+	GCUUGCGGCGAGACAUGGUGGGCU	24	8238
  BCL11A-6625	+	CAGUGCAGAAGUUUAUCU	18	8239
  BCL11A-6626	+	CCAGUGCAGAAGUUUAUCU	19	8240
  BCL11A-6627	+	UCCAGUGCAGAAGUUUAUCU	20	8241
  BCL11A-6628	+	CUCCAGUGCAGAAGUUUAUCU	21	8242
  BCL11A-6629	+	CCUCCAGUGCAGAAGUUUAUCU	22	8243
  BCL11A-6630	+	CCCUCCAGUGCAGAAGUUUAUCU	23	8244
  BCL11A-6631	+	CCCCUCCAGUGCAGAAGUUUAUCU	24	8245
  BCL11A-6632	+	CUGGCACUGCCCACAGGU	18	8246
  BCL11A-6633	+	UCUGGCACUGCCCACAGGU	19	8247
  BCL11A-6634	+	AUCUGGCACUGCCCACAGGU	20	8248
  BCL11A-6635	+	CAUCUGGCACUGCCCACAGGU	21	8249
  BCL11A-6636	+	UCAUCUGGCACUGCCCACAGGU	22	8250
  BCL11A-6637	+	UUCAUCUGGCACUGCCCACAGGU	23	8251
  BCL11A-6638	+	GUUCAUCUGGCACUGCCCACAGGU	24	8252
  BCL11A-6639	+	AAGAGGCUCGGCUGUGGU	18	8253
  BCL11A-6640	+	CAAGAGGCUCGGCUGUGGU	19	8254
  BCL11A-5366	+	UCAAGAGGCUCGGCUGUGGU	20	8255
  BCL11A-6641	+	UUCAAGAGGCUCGGCUGUGGU	21	8256
  BCL11A-6642	+	CUUCAAGAGGCUCGGCUGUGGU	22	8257
  BCL11A-6643	+	GCUUCAAGAGGCUCGGCUGUGGU	23	8258
  BCL11A-6644	+	GGCUUCAAGAGGCUCGGCUGUGGU	24	8259
  BCL11A-6645	+	CCUGCUAUGUGUUCCUGU	18	8260
  BCL11A-6646	+	ACCUGCUAUGUGUUCCUGU	19	8261
  BCL11A-6647	+	UACCUGCUAUGUGUUCCUGU	20	8262
  BCL11A-6648	+	UUACCUGCUAUGUGUUCCUGU	21	8263
  BCL11A-6649	+	UUUACCUGCUAUGUGUUCCUGU	22	8264
  BCL11A-6650	+	AUUUACCUGCUAUGUGUUCCUGU	23	8265
  BCL11A-6651	+	CAUUUACCUGCUAUGUGUUCCUGU	24	8266
  BCL11A-6652	+	GGAGGUCAUGAUCCCCUU	18	8267
  BCL11A-6653	+	AGGAGGUCAUGAUCCCCUU	19	8268
  BCL11A-6654	+	GAGGAGGUCAUGAUCCCCUU	20	8269
  BCL11A-6655	+	UGAGGAGGUCAUGAUCCCCUU	21	8270
  BCL11A-6656	+	GUGAGGAGGUCAUGAUCCCCUU	22	8271
  BCL11A-6657	+	GGUGAGGAGGUCAUGAUCCCCUU	23	8272
  BCL11A-6658	+	AGGUGAGGAGGUCAUGAUCCCCUU	24	8273
  BCL11A-6659	+	CUGCUAUGUGUUCCUGUU	18	8274
  BCL11A-6660	+	CCUGCUAUGUGUUCCUGUU	19	8275
  BCL11A-5513	+	ACCUGCUAUGUGUUCCUGUU	20	8276
  BCL11A-6661	+	UACCUGCUAUGUGUUCCUGUU	21	8277
  BCL11A-6662	+	UUACCUGCUAUGUGUUCCUGUU	22	8278
  BCL11A-6663	+	UUUACCUGCUAUGUGUUCCUGUU	23	8279
  BCL11A-6664	+	AUUUACCUGCUAUGUGUUCCUGUU	24	8280
  BCL11A-6665	-	AUUUUUAUCGAGCACAAA	18	8281
  BCL11A-6666	-	UAUUUUUAUCGAGCACAAA	19	8282
  BCL11A-5342	-	UUAUUUUUAUCGAGCACAAA	20	8283
  BCL11A-6667	-	CUUAUUUUUAUCGAGCACAAA	21	8284
  BCL11A-6668	-	UCUUAUUUUUAUCGAGCACAAA	22	8285
  BCL11A-6669	-	UUCUUAUUUUUAUCGAGCACAAA	23	8286
  BCL11A-6670	-	AUUCUUAUUUUUAUCGAGCACAAA	24	8287
  BCL11A-6671	-	AGAGGAAUUUGCCCCAAA	18	8288
  BCL11A-6672	-	UAGAGGAAUUUGCCCCAAA	19	8289
  BCL11A-6673	-	CUAGAGGAAUUUGCCCCAAA	20	8290
  BCL11A-6674	-	UCUAGAGGAAUUUGCCCCAAA	21	8291
  BCL11A-6675	-	AUCUAGAGGAAUUUGCCCCAAA	22	8292
  BCL11A-6676	-	CAUCUAGAGGAAUUUGCCCCAAA	23	8293
  BCL11A-6677	-	UCAUCUAGAGGAAUUUGCCCCAAA	24	8294
  BCL11A-6678	-	CCCCAGCACUUAAGCAAA	18	8295
  BCL11A-6679	-	ACCCCAGCACUUAAGCAAA	19	8296
  BCL11A-5443	-	AACCCCAGCACUUAAGCAAA	20	8297
  BCL11A-6680	-	AAACCCCAGCACUUAAGCAAA	21	8298
  BCL11A-6681	-	CAAACCCCAGCACUUAAGCAAA	22	8299
  BCL11A-6682	-	GCAAACCCCAGCACUUAAGCAAA	23	8300
  BCL11A-6683	-	GGCAAACCCCAGCACUUAAGCAAA	24	8301
  BCL11A-6684	-	UAUUUUUAUCGAGCACAA	18	8302
  BCL11A-6685	-	UUAUUUUUAUCGAGCACAA	19	8303
  BCL11A-6686	-	CUUAUUUUUAUCGAGCACAA	20	8304
  BCL11A-6687	-	UCUUAUUUUUAUCGAGCACAA	21	8305
  BCL11A-6688	-	UUCUUAUUUUUAUCGAGCACAA	22	8306
  BCL11A-6689	-	AUUCUUAUUUUUAUCGAGCACAA	23	8307
  BCL11A-6690	-	CAUUCUUAUUUUUAUCGAGCACAA	24	8308
  BCL11A-6691	-	CACCUUCCCCUUCACCAA	18	8309
  BCL11A-6692	-	CCACCUUCCCCUUCACCAA	19	8310
  BCL11A-6693	-	GCCACCUUCCCCUUCACCAA	20	8311
  BCL11A-6694	-	AGCCACCUUCCCCUUCACCAA	21	8312
  BCL11A-6695	-	AAGCCACCUUCCCCUUCACCAA	22	8313
  BCL11A-6696	-	UAAGCCACCUUCCCCUUCACCAA	23	8314
  BCL11A-6697	-	AUAAGCCACCUUCCCCUUCACCAA	24	8315
  BCL11A-6698	-	ACCCCAGCACUUAAGCAA	18	8316
  BCL11A-6699	-	AACCCCAGCACUUAAGCAA	19	8317
  BCL11A-6700	-	AAACCCCAGCACUUAAGCAA	20	8318
  BCL11A-6701	-	CAAACCCCAGCACUUAAGCAA	21	8319
  BCL11A-6702	-	GCAAACCCCAGCACUUAAGCAA	22	8320
  BCL11A-6703	-	GGCAAACCCCAGCACUUAAGCAA	23	8321
  BCL11A-6704	-	AGGCAAACCCCAGCACUUAAGCAA	24	8322
  BCL11A-6705	-	GGAACACAUAGCAGGUAA	18	8323
  BCL11A-6706	-	AGGAACACAUAGCAGGUAA	19	8324
  BCL11A-6707	-	CAGGAACACAUAGCAGGUAA	20	8325
  BCL11A-6708	-	ACAGGAACACAUAGCAGGUAA	21	8326
  BCL11A-6709	-	AACAGGAACACAUAGCAGGUAA	22	8327
  BCL11A-6710	-	AAACAGGAACACAUAGCAGGUAA	23	8328
  BCL11A-6711	-	CAAACAGGAACACAUAGCAGGUAA	24	8329
  BCL11A-6712	-	CUCCCCUCGUUCUGCACA	18	8330
  BCL11A-6713	-	CCUCCCCUCGUUCUGCACA	19	8331
  BCL11A-5448	-	UCCUCCCCUCGUUCUGCACA	20	8332
  BCL11A-6714	-	CUCCUCCCCUCGUUCUGCACA	21	8333
  BCL11A-6715	-	UCUCCUCCCCUCGUUCUGCACA	22	8334
  BCL11A-6716	-	CUCUCCUCCCCUCGUUCUGCACA	23	8335
  BCL11A-6717	-	CCUCUCCUCCCCUCGUUCUGCACA	24	8336
  BCL11A-6718	-	UGCCAGAUGAACUUCCCA	18	8337
  BCL11A-6719	-	GUGCCAGAUGAACUUCCCA	19	8338
  BCL11A-6720	-	AGUGCCAGAUGAACUUCCCA	20	8339
  BCL11A-6721	-	CAGUGCCAGAUGAACUUCCCA	21	8340
  BCL11A-6722	-	GCAGUGCCAGAUGAACUUCCCA	22	8341
  BCL11A-6723	-	GGCAGUGCCAGAUGAACUUCCCA	23	8342
  BCL11A-6724	-	GGGCAGUGCCAGAUGAACUUCCCA	24	8343
  BCL11A-6725	-	GCAGGUAAAUGAGAAGCA	18	8344
  BCL11A-6726	-	AGCAGGUAAAUGAGAAGCA	19	8345
  BCL11A-5451	-	UAGCAGGUAAAUGAGAAGCA	20	8346
  BCL11A-6727	-	AUAGCAGGUAAAUGAGAAGCA	21	8347
  BCL11A-6728	-	CAUAGCAGGUAAAUGAGAAGCA	22	8348
  BCL11A-6729	-	ACAUAGCAGGUAAAUGAGAAGCA	23	8349
  BCL11A-6730	-	CACAUAGCAGGUAAAUGAGAAGCA	24	8350
  BCL11A-6731	-	CACAGAUAAACUUCUGCA	18	8351
  BCL11A-6732	-	UCACAGAUAAACUUCUGCA	19	8352
  BCL11A-6733	-	UUCACAGAUAAACUUCUGCA	20	8353
  BCL11A-6734	-	UUUCACAGAUAAACUUCUGCA	21	8354
  BCL11A-6735	-	CUUUCACAGAUAAACUUCUGCA	22	8355
  BCL11A-6736	-	UCUUUCACAGAUAAACUUCUGCA	23	8356
  BCL11A-6737	-	UUCUUUCACAGAUAAACUUCUGCA	24	8357
  BCL11A-6738	-	CCCGUUGGGAGCUCCAGA	18	8358
  BCL11A-6739	-	GCCCGUUGGGAGCUCCAGA	19	8359
  BCL11A-5453	-	GGCCCGUUGGGAGCUCCAGA	20	8360
  BCL11A-6740	-	CGGCCCGUUGGGAGCUCCAGA	21	8361
  BCL11A-6741	-	ACGGCCCGUUGGGAGCUCCAGA	22	8362
  BCL11A-6742	-	CACGGCCCGUUGGGAGCUCCAGA	23	8363
  BCL11A-6743	-	CCACGGCCCGUUGGGAGCUCCAGA	24	8364
  BCL11A-6744	-	GUUUAUCAACGUCAUCUA	18	8365
  BCL11A-6745	-	UGUUUAUCAACGUCAUCUA	19	8366
  BCL11A-6746	-	UUGUUUAUCAACGUCAUCUA	20	8367
  BCL11A-6747	-	AUUGUUUAUCAACGUCAUCUA	21	8368
  BCL11A-6748	-	GAUUGUUUAUCAACGUCAUCUA	22	8369
  BCL11A-6749	-	CGAUUGUUUAUCAACGUCAUCUA	23	8370
  BCL11A-6750	-	ACGAUUGUUUAUCAACGUCAUCUA	24	8371
  BCL11A-6751	-	GGGACAUUCUUAUUUUUA	18	8372
  BCL11A-6752	-	GGGGACAUUCUUAUUUUUA	19	8373
  BCL11A-6753	-	GGGGGACAUUCUUAUUUUUA	20	8374
  BCL11A-6754	-	UGGGGGACAUUCUUAUUUUUA	21	8375
  BCL11A-6755	-	UUGGGGGACAUUCUUAUUUUUA	22	8376
  BCL11A-6756	-	AUUGGGGGACAUUCUUAUUUUUA	23	8377
  BCL11A-6757	-	CAUUGGGGGACAUUCUUAUUUUUA	24	8378
  BCL11A-6758	-	GAGGAAUUUGCCCCAAAC	18	8379
  BCL11A-6759	-	AGAGGAAUUUGCCCCAAAC	19	8380
  BCL11A-5457	-	UAGAGGAAUUUGCCCCAAAC	20	8381
  BCL11A-6760	-	CUAGAGGAAUUUGCCCCAAAC	21	8382
  BCL11A-6761	-	UCUAGAGGAAUUUGCCCCAAAC	22	8383
  BCL11A-6762	-	AUCUAGAGGAAUUUGCCCCAAAC	23	8384
  BCL11A-6763	-	CAUCUAGAGGAAUUUGCCCCAAAC	24	8385
  BCL11A-6764	-	ACAGAUAAACUUCUGCAC	18	8386
  BCL11A-6765	-	CACAGAUAAACUUCUGCAC	19	8387
  BCL11A-5348	-	UCACAGAUAAACUUCUGCAC	20	8388
  BCL11A-6766	-	UUCACAGAUAAACUUCUGCAC	21	8389
  BCL11A-6767	-	UUUCACAGAUAAACUUCUGCAC	22	8390
  BCL11A-6768	-	CUUUCACAGAUAAACUUCUGCAC	23	8391
  BCL11A-6769	-	UCUUUCACAGAUAAACUUCUGCAC	24	8392
  BCL11A-6770	-	CCUCCCCUCGUUCUGCAC	18	8393
  BCL11A-6771	-	UCCUCCCCUCGUUCUGCAC	19	8394
  BCL11A-6772	-	CUCCUCCCCUCGUUCUGCAC	20	8395
  BCL11A-6773	-	UCUCCUCCCCUCGUUCUGCAC	21	8396
  BCL11A-6774	-	CUCUCCUCCCCUCGUUCUGCAC	22	8397
  BCL11A-6775	-	CCUCUCCUCCCCUCGUUCUGCAC	23	8398
  BCL11A-6776	-	GCCUCUCCUCCCCUCGUUCUGCAC	24	8399
  BCL11A-6777	-	AAAAAAGCAUCCAAUCCC	18	8400
  BCL11A-6778	-	GAAAAAAGCAUCCAAUCCC	19	8401
  BCL11A-6779	-	UGAAAAAAGCAUCCAAUCCC	20	8402
  BCL11A-6780	-	AUGAAAAAAGCAUCCAAUCCC	21	8403
  BCL11A-6781	-	GAUGAAAAAAGCAUCCAAUCCC	22	8404
  BCL11A-6782	-	AGAUGAAAAAAGCAUCCAAUCCC	23	8405
  BCL11A-6783	-	GAGAUGAAAAAAGCAUCCAAUCCC	24	8406
  BCL11A-6784	-	AGCAGGUAAAUGAGAAGC	18	8407
  BCL11A-6785	-	UAGCAGGUAAAUGAGAAGC	19	8408
  BCL11A-6786	-	AUAGCAGGUAAAUGAGAAGC	20	8409
  BCL11A-6787	-	CAUAGCAGGUAAAUGAGAAGC	21	8410
  BCL11A-6788	-	ACAUAGCAGGUAAAUGAGAAGC	22	8411
  BCL11A-6789	-	CACAUAGCAGGUAAAUGAGAAGC	23	8412
  BCL11A-6790	-	ACACAUAGCAGGUAAAUGAGAAGC	24	8413
  BCL11A-6791	-	GAGCUCUAAUCCCCACGC	18	8414
  BCL11A-6792	-	GGAGCUCUAAUCCCCACGC	19	8415
  BCL11A-6793	-	UGGAGCUCUAAUCCCCACGC	20	8416
  BCL11A-6794	-	AUGGAGCUCUAAUCCCCACGC	21	8417
  BCL11A-6795	-	CAUGGAGCUCUAAUCCCCACGC	22	8418
  BCL11A-6796	-	ACAUGGAGCUCUAAUCCCCACGC	23	8419
  BCL11A-6797	-	CACAUGGAGCUCUAAUCCCCACGC	24	8420
  BCL11A-6798	-	UUGGCAUCCAGGUCACGC	18	8421
  BCL11A-6799	-	GUUGGCAUCCAGGUCACGC	19	8422
  BCL11A-6800	-	GGUUGGCAUCCAGGUCACGC	20	8423
  BCL11A-6801	-	AGGUUGGCAUCCAGGUCACGC	21	8424
  BCL11A-6802	-	GAGGUUGGCAUCCAGGUCACGC	22	8425
  BCL11A-6803	-	GGAGGUUGGCAUCCAGGUCACGC	23	8426
  BCL11A-6804	-	UGGAGGUUGGCAUCCAGGUCACGC	24	8427
  BCL11A-6805	-	UUGUUUAUCAACGUCAUC	18	8428
  BCL11A-6806	-	AUUGUUUAUCAACGUCAUC	19	8429
  BCL11A-6807	-	GAUUGUUUAUCAACGUCAUC	20	8430
  BCL11A-6808	-	CGAUUGUUUAUCAACGUCAUC	21	8431
  BCL11A-6809	-	ACGAUUGUUUAUCAACGUCAUC	22	8432
  BCL11A-6810	-	GACGAUUGUUUAUCAACGUCAUC	23	8433
  BCL11A-6811	-	UGACGAUUGUUUAUCAACGUCAUC	24	8434
  BCL11A-6812	-	CAACCACAGCCGAGCCUC	18	8435
  BCL11A-6813	-	CCAACCACAGCCGAGCCUC	19	8436
  BCL11A-6814	-	UCCAACCACAGCCGAGCCUC	20	8437
  BCL11A-6815	-	CUCCAACCACAGCCGAGCCUC	21	8438
  BCL11A-6816	-	UCUCCAACCACAGCCGAGCCUC	22	8439
  BCL11A-6817	-	UUCUCCAACCACAGCCGAGCCUC	23	8440
  BCL11A-6818	-	UUUCUCCAACCACAGCCGAGCCUC	24	8441
  BCL11A-6819	-	ACGGCCCGUUGGGAGCUC	18	8442
  BCL11A-6820	-	CACGGCCCGUUGGGAGCUC	19	8443
  BCL11A-6821	-	CCACGGCCCGUUGGGAGCUC	20	8444
  BCL11A-6822	-	ACCACGGCCCGUUGGGAGCUC	21	8445
  BCL11A-6823	-	GACCACGGCCCGUUGGGAGCUC	22	8446
  BCL11A-6824	-	AGACCACGGCCCGUUGGGAGCUC	23	8447
  BCL11A-6825	-	CAGACCACGGCCCGUUGGGAGCUC	24	8448
  BCL11A-6826	-	AUUAUUUUGCAGGUAAAG	18	8449
  BCL11A-6827	-	UAUUAUUUUGCAGGUAAAG	19	8450
  BCL11A-6828	-	GUAUUAUUUUGCAGGUAAAG	20	8451
  BCL11A-6829	-	UGUAUUAUUUUGCAGGUAAAG	21	8452
  BCL11A-6830	-	UUGUAUUAUUUUGCAGGUAAAG	22	8453
  BCL11A-6831	-	GUUGUAUUAUUUUGCAGGUAAAG	23	8454
  BCL11A-6832	-	UGUUGUAUUAUUUUGCAGGUAAAG	24	8455
  BCL11A-6833	-	AGGUAAAUGAGAAGCAAG	18	8456
  BCL11A-6834	-	CAGGUAAAUGAGAAGCAAG	19	8457
  BCL11A-6835	-	GCAGGUAAAUGAGAAGCAAG	20	8458
  BCL11A-6836	-	AGCAGGUAAAUGAGAAGCAAG	21	8459
  BCL11A-6837	-	UAGCAGGUAAAUGAGAAGCAAG	22	8460
  BCL11A-6838	-	AUAGCAGGUAAAUGAGAAGCAAG	23	8461
  BCL11A-6839	-	CAUAGCAGGUAAAUGAGAAGCAAG	24	8462
  BCL11A-6840	-	CCGCAGGGUAUUUGUAAG	18	8463
  BCL11A-6841	-	CCCGCAGGGUAUUUGUAAG	19	8464
  BCL11A-6842	-	CCCCGCAGGGUAUUUGUAAG	20	8465
  BCL11A-6843	-	GCCCCGCAGGGUAUUUGUAAG	21	8466
  BCL11A-6844	-	UGCCCCGCAGGGUAUUUGUAAG	22	8467
  BCL11A-6845	-	AUGCCCCGCAGGGUAUUUGUAAG	23	8468
  BCL11A-6846	-	UAUGCCCCGCAGGGUAUUUGUAAG	24	8469
  BCL11A-6847	-	UUGUUUCUCCAACCACAG	18	8470
  BCL11A-6848	-	UUUGUUUCUCCAACCACAG	19	8471
  BCL11A-6849	-	UUUUGUUUCUCCAACCACAG	20	8472
  BCL11A-6850	-	CUUUUGUUUCUCCAACCACAG	21	8473
  BCL11A-6851	-	GCUUUUGUUUCUCCAACCACAG	22	8474
  BCL11A-6852	-	UGCUUUUGUUUCUCCAACCACAG	23	8475
  BCL11A-6853	-	GUGCUUUUGUUUCUCCAACCACAG	24	8476
  BCL11A-6854	-	ACCUGUGGGCAGUGCCAG	18	8477
  BCL11A-6855	-	CACCUGUGGGCAGUGCCAG	19	8478
  BCL11A-6856	-	UCACCUGUGGGCAGUGCCAG	20	8479
  BCL11A-6857	-	CUCACCUGUGGGCAGUGCCAG	21	8480
  BCL11A-6858	-	CCUCACCUGUGGGCAGUGCCAG	22	8481
  BCL11A-6859	-	UCCUCACCUGUGGGCAGUGCCAG	23	8482
  BCL11A-6860	-	CUCCUCACCUGUGGGCAGUGCCAG	24	8483
  BCL11A-6861	-	GCCCGUUGGGAGCUCCAG	18	8484
  BCL11A-6862	-	GGCCCGUUGGGAGCUCCAG	19	8485
  BCL11A-6863	-	CGGCCCGUUGGGAGCUCCAG	20	8486
  BCL11A-6864	-	ACGGCCCGUUGGGAGCUCCAG	21	8487
  BCL11A-6865	-	CACGGCCCGUUGGGAGCUCCAG	22	8488
  BCL11A-6866	-	CCACGGCCCGUUGGGAGCUCCAG	23	8489
  BCL11A-6867	-	ACCACGGCCCGUUGGGAGCUCCAG	24	8490
  BCL11A-6868	-	UCCCCUUCACCAAUCGAG	18	8491
  BCL11A-6869	-	UUCCCCUUCACCAAUCGAG	19	8492
  BCL11A-6870	-	CUUCCCCUUCACCAAUCGAG	20	8493
  BCL11A-6871	-	CCUUCCCCUUCACCAAUCGAG	21	8494
  BCL11A-6872	-	ACCUUCCCCUUCACCAAUCGAG	22	8495
  BCL11A-6873	-	CACCUUCCCCUUCACCAAUCGAG	23	8496
  BCL11A-6874	-	CCACCUUCCCCUUCACCAAUCGAG	24	8497
  BCL11A-6875	-	GAACCAGACCACGGCCCG	18	8498
  BCL11A-6876	-	UGAACCAGACCACGGCCCG	19	8499
  BCL11A-6877	-	AUGAACCAGACCACGGCCCG	20	8500
  BCL11A-6878	-	GAUGAACCAGACCACGGCCCG	21	8501
  BCL11A-6879	-	UGAUGAACCAGACCACGGCCCG	22	8502
  BCL11A-6880	-	AUGAUGAACCAGACCACGGCCCG	23	8503
  BCL11A-6881	-	GAUGAUGAACCAGACCACGGCCCG	24	8504
  BCL11A-6882	-	AAAAAGCAUCCAAUCCCG	18	8505
  BCL11A-6883	-	AAAAAAGCAUCCAAUCCCG	19	8506
  BCL11A-5358	-	GAAAAAAGCAUCCAAUCCCG	20	8507
  BCL11A-6884	-	UGAAAAAAGCAUCCAAUCCCG	21	8508
  BCL11A-6885	-	AUGAAAAAAGCAUCCAAUCCCG	22	8509
  BCL11A-6886	-	GAUGAAAAAAGCAUCCAAUCCCG	23	8510
  BCL11A-6887	-	AGAUGAAAAAAGCAUCCAAUCCCG	24	8511
  BCL11A-6888	-	GAUAAACUUCUGCACUGG	18	8512
  BCL11A-6889	-	AGAUAAACUUCUGCACUGG	19	8513
  BCL11A-5360	-	CAGAUAAACUUCUGCACUGG	20	8514
  BCL11A-6890	-	ACAGAUAAACUUCUGCACUGG	21	8515
  BCL11A-6891	-	CACAGAUAAACUUCUGCACUGG	22	8516
  BCL11A-6892	-	UCACAGAUAAACUUCUGCACUGG	23	8517
  BCL11A-6893	-	UUCACAGAUAAACUUCUGCACUGG	24	8518
  BCL11A-6894	-	AAGCCAUUCUUACAGAUG	18	8519
  BCL11A-6895	-	GAAGCCAUUCUUACAGAUG	19	8520
  BCL11A-6896	-	UGAAGCCAUUCUUACAGAUG	20	8521
  BCL11A-6897	-	UUGAAGCCAUUCUUACAGAUG	21	8522
  BCL11A-6898	-	CUUGAAGCCAUUCUUACAGAUG	22	8523
  BCL11A-6899	-	UCUUGAAGCCAUUCUUACAGAUG	23	8524
  BCL11A-6900	-	CUCUUGAAGCCAUUCUUACAGAUG	24	8525
  BCL11A-6901	-	AGAUAAACUUCUGCACUG	18	8526
  BCL11A-6902	-	CAGAUAAACUUCUGCACUG	19	8527
  BCL11A-6903	-	ACAGAUAAACUUCUGCACUG	20	8528
  BCL11A-6904	-	CACAGAUAAACUUCUGCACUG	21	8529
  BCL11A-6905	-	UCACAGAUAAACUUCUGCACUG	22	8530
  BCL11A-6906	-	UUCACAGAUAAACUUCUGCACUG	23	8531
  BCL11A-6907	-	UUUCACAGAUAAACUUCUGCACUG	24	8532
  BCL11A-6908	-	CAGAUGAACUUCCCAUUG	18	8533
  BCL11A-6909	-	CCAGAUGAACUUCCCAUUG	19	8534
  BCL11A-5499	-	GCCAGAUGAACUUCCCAUUG	20	8535
  BCL11A-6910	-	UGCCAGAUGAACUUCCCAUUG	21	8536
  BCL11A-6911	-	GUGCCAGAUGAACUUCCCAUUG	22	8537
  BCL11A-6912	-	AGUGCCAGAUGAACUUCCCAUUG	23	8538
  BCL11A-6913	-	CAGUGCCAGAUGAACUUCCCAUUG	24	8539
  BCL11A-6914	-	AACACAUAGCAGGUAAAU	18	8540
  BCL11A-6915	-	GAACACAUAGCAGGUAAAU	19	8541
  BCL11A-6916	-	GGAACACAUAGCAGGUAAAU	20	8542
  BCL11A-6917	-	AGGAACACAUAGCAGGUAAAU	21	8543
  BCL11A-6918	-	CAGGAACACAUAGCAGGUAAAU	22	8544
  BCL11A-6919	-	ACAGGAACACAUAGCAGGUAAAU	23	8545
  BCL11A-6920	-	AACAGGAACACAUAGCAGGUAAAU	24	8546
  BCL11A-6921	-	GCCAGAUGAACUUCCCAU	18	8547
  BCL11A-6922	-	UGCCAGAUGAACUUCCCAU	19	8548
  BCL11A-5503	-	GUGCCAGAUGAACUUCCCAU	20	8549
  BCL11A-6923	-	AGUGCCAGAUGAACUUCCCAU	21	8550
  BCL11A-6924	-	CAGUGCCAGAUGAACUUCCCAU	22	8551
  BCL11A-6925	-	GCAGUGCCAGAUGAACUUCCCAU	23	8552
  BCL11A-6926	-	GGCAGUGCCAGAUGAACUUCCCAU	24	8553
  BCL11A-6927	-	AUCAUGACCUCCUCACCU	18	8554
  BCL11A-6928	-	GAUCAUGACCUCCUCACCU	19	8555
  BCL11A-6929	-	GGAUCAUGACCUCCUCACCU	20	8556
  BCL11A-6930	-	GGGAUCAUGACCUCCUCACCU	21	8557
  BCL11A-6931	-	GGGGAUCAUGACCUCCUCACCU	22	8558
  BCL11A-6932	-	AGGGGAUCAUGACCUCCUCACCU	23	8559
  BCL11A-6933	-	AAGGGGAUCAUGACCUCCUCACCU	24	8560
  BCL11A-6934	-	GCAAUGGCAGCCUCUGCU	18	8561
  BCL11A-6935	-	UGCAAUGGCAGCCUCUGCU	19	8562
  BCL11A-6936	-	AUGCAAUGGCAGCCUCUGCU	20	8563
  BCL11A-6937	-	AAUGCAAUGGCAGCCUCUGCU	21	8564
  BCL11A-6938	-	CAAUGCAAUGGCAGCCUCUGCU	22	8565
  BCL11A-6939	-	ACAAUGCAAUGGCAGCCUCUGCU	23	8566
  BCL11A-6940	-	AACAAUGCAAUGGCAGCCUCUGCU	24	8567
  BCL11A-6941	-	AACCAGACCACGGCCCGU	18	8568
  BCL11A-6942	-	GAACCAGACCACGGCCCGU	19	8569
  BCL11A-5363	-	UGAACCAGACCACGGCCCGU	20	8570
  BCL11A-6943	-	AUGAACCAGACCACGGCCCGU	21	8571
  BCL11A-6944	-	GAUGAACCAGACCACGGCCCGU	22	8572
  BCL11A-6945	-	UGAUGAACCAGACCACGGCCCGU	23	8573
  BCL11A-6946	-	AUGAUGAACCAGACCACGGCCCGU	24	8574
  BCL11A-6947	-	CCAGAUGAACUUCCCAUU	18	8575
  BCL11A-6948	-	GCCAGAUGAACUUCCCAUU	19	8576
  BCL11A-5511	-	UGCCAGAUGAACUUCCCAUU	20	8577
  BCL11A-6949	-	GUGCCAGAUGAACUUCCCAUU	21	8578
  BCL11A-6950	-	AGUGCCAGAUGAACUUCCCAUU	22	8579
  BCL11A-6951	-	CAGUGCCAGAUGAACUUCCCAUU	23	8580
  BCL11A-6952	-	GCAGUGCCAGAUGAACUUCCCAUU	24	8581
  BCL11A-6953	-	ACCAGACCACGGCCCGUU	18	8582
  BCL11A-6954	-	AACCAGACCACGGCCCGUU	19	8583
  BCL11A-5512	-	GAACCAGACCACGGCCCGUU	20	8584
  BCL11A-6955	-	UGAACCAGACCACGGCCCGUU	21	8585
  BCL11A-6956	-	AUGAACCAGACCACGGCCCGUU	22	8586
  BCL11A-6957	-	GAUGAACCAGACCACGGCCCGUU	23	8587
  BCL11A-6958	-	UGAUGAACCAGACCACGGCCCGUU	24	8588

• Table 16D 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 500 bp 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 16D
  4th Tier

  	DNA		Target Site	SEQ ID
  gRNA Name	Strand	Targeting Domain	Length	NO:
  BCL11A-6959	+	GUAUUCUUAGCAGGUUAA	18	8589
  BCL11A-6960	+	GGUAUUCUUAGCAGGUUAA	19	8590
  BCL11A-5890	+	UGGUAUUCUUAGCAGGUUAA	20	8591
  BCL11A-6961	+	CUGGUAUUCUUAGCAGGUUAA	21	8592
  BCL11A-6962	+	CCUGGUAUUCUUAGCAGGUUAA	22	8593
  BCL11A-6963	+	UCCUGGUAUUCUUAGCAGGUUAA	23	8594
  BCL11A-6964	+	AUCCUGGUAUUCUUAGCAGGUUAA	24	8595
  BCL11A-6965	+	CGGGAGGCUCCAUAGCCA	18	8596
  BCL11A-6966	+	GCGGGAGGCUCCAUAGCCA	19	8597
  BCL11A-6967	+	GGCGGGAGGCUCCAUAGCCA	20	8598
  BCL11A-6968	+	UGGCGGGAGGCUCCAUAGCCA	21	8599
  BCL11A-6969	+	AUGGCGGGAGGCUCCAUAGCCA	22	8600
  BCL11A-6970	+	CAUGGCGGGAGGCUCCAUAGCCA	23	8601
  BCL11A-6971	+	CCAUGGCGGGAGGCUCCAUAGCCA	24	8602
  BCL11A-6972	+	GGUCCGACUCGCCGGCCA	18	8603
  BCL11A-6973	+	CGGUCCGACUCGCCGGCCA	19	8604
  BCL11A-6974	+	GCGGUCCGACUCGCCGGCCA	20	8605
  BCL11A-6975	+	UGCGGUCCGACUCGCCGGCCA	21	8606
  BCL11A-6976	+	AUGCGGUCCGACUCGCCGGCCA	22	8607
  BCL11A-6977	+	UAUGCGGUCCGACUCGCCGGCCA	23	8608
  BCL11A-6978	+	CUAUGCGGUCCGACUCGCCGGCCA	24	8609
  BCL11A-6979	+	AGUCUCCGAAGCUAAGGA	18	8610
  BCL11A-6980	+	GAGUCUCCGAAGCUAAGGA	19	8611
  BCL11A-5923	+	GGAGUCUCCGAAGCUAAGGA	20	8612
  BCL11A-6981	+	UGGAGUCUCCGAAGCUAAGGA	21	8613
  BCL11A-6982	+	CUGGAGUCUCCGAAGCUAAGGA	22	8614
  BCL11A-6983	+	UCUGGAGUCUCCGAAGCUAAGGA	23	8615
  BCL11A-6984	+	GUCUGGAGUCUCCGAAGCUAAGGA	24	8616
  BCL11A-6985	+	GGACUAAACAGGGGGGGA	18	8617
  BCL11A-6986	+	UGGACUAAACAGGGGGGGA	19	8618
  BCL11A-6987	+	GUGGACUAAACAGGGGGGGA	20	8619
  BCL11A-6988	+	GGUGGACUAAACAGGGGGGGA	21	8620
  BCL11A-6989	+	UGGUGGACUAAACAGGGGGGGA	22	8621
  BCL11A-6990	+	GUGGUGGACUAAACAGGGGGGGA	23	8622
  BCL11A-6991	+	GGUGGUGGACUAAACAGGGGGGGA	24	8623
  BCL11A-6992	+	UUCUGCACCUAGUCCUGA	18	8624
  BCL11A-6993	+	AUUCUGCACCUAGUCCUGA	19	8625
  BCL11A-5937	+	CAUUCUGCACCUAGUCCUGA	20	8626
  BCL11A-6994	+	ACAUUCUGCACCUAGUCCUGA	21	8627
  BCL11A-6995	+	GACAUUCUGCACCUAGUCCUGA	22	8628
  BCL11A-6996	+	GGACAUUCUGCACCUAGUCCUGA	23	8629
  BCL11A-6997	+	AGGACAUUCUGCACCUAGUCCUGA	24	8630
  BCL11A-6998	+	GCACCCUGUCAAAGGCAC	18	8631
  BCL11A-6999	+	AGCACCCUGUCAAAGGCAC	19	8632
  BCL11A-7000	+	CAGCACCCUGUCAAAGGCAC	20	8633
  BCL11A-7001	+	GCAGCACCCUGUCAAAGGCAC	21	8634
  BCL11A-7002	+	CGCAGCACCCUGUCAAAGGCAC	22	8635
  BCL11A-7003	+	CCGCAGCACCCUGUCAAAGGCAC	23	8636
  BCL11A-7004	+	ACCGCAGCACCCUGUCAAAGGCAC	24	8637
  BCL11A-7005	+	UAAGUAGAUUCUUAAUCC	18	8638
  BCL11A-7006	+	CUAAGUAGAUUCUUAAUCC	19	8639
  BCL11A-7007	+	UCUAAGUAGAUUCUUAAUCC	20	8640
  BCL11A-7008	+	UUCUAAGUAGAUUCUUAAUCC	21	8641
  BCL11A-7009	+	UUUCUAAGUAGAUUCUUAAUCC	22	8642
  BCL11A-7010	+	CUUUCUAAGUAGAUUCUUAAUCC	23	8643
  BCL11A-7011	+	GCUUUCUAAGUAGAUUCUUAAUCC	24	8644
  BCL11A-7012	+	GGCGGCUUGCUACCUGGC	18	8645
  BCL11A-7013	+	GGGCGGCUUGCUACCUGGC	19	8646
  BCL11A-6036	+	AGGGCGGCUUGCUACCUGGC	20	8647
  BCL11A-7014	+	AAGGGCGGCUUGCUACCUGGC	21	8648
  BCL11A-7015	+	GAAGGGCGGCUUGCUACCUGGC	22	8649
  BCL11A-7016	+	GGAAGGGCGGCUUGCUACCUGGC	23	8650
  BCL11A-7017	+	AGGAAGGGCGGCUUGCUACCUGGC	24	8651
  BCL11A-7018	+	GCGCUUCAGCUUGCUGGC	18	8652
  BCL11A-7019	+	GGCGCUUCAGCUUGCUGGC	19	8653
  BCL11A-7020	+	UGGCGCUUCAGCUUGCUGGC	20	8654
  BCL11A-7021	+	GUGGCGCUUCAGCUUGCUGGC	21	8655
  BCL11A-7022	+	UGUGGCGCUUCAGCUUGCUGGC	22	8656
  BCL11A-7023	+	AUGUGGCGCUUCAGCUUGCUGGC	23	8657
  BCL11A-7024	+	CAUGUGGCGCUUCAGCUUGCUGGC	24	8658
  BCL11A-7025	+	CUCCUCGUCCCCGUUCUC	18	8659
  BCL11A-7026	+	CCUCCUCGUCCCCGUUCUC	19	8660
  BCL11A-6050	+	UCCUCCUCGUCCCCGUUCUC	20	8661
  BCL11A-7027	+	UUCCUCCUCGUCCCCGUUCUC	21	8662
  BCL11A-7028	+	CUUCCUCCUCGUCCCCGUUCUC	22	8663
  BCL11A-7029	+	UCUUCCUCCUCGUCCCCGUUCUC	23	8664
  BCL11A-7030	+	CUCUUCCUCCUCGUCCCCGUUCUC	24	8665
  BCL11A-7031	+	AGGCAAAAGGCGAUUGUC	18	8666
  BCL11A-7032	+	GAGGCAAAAGGCGAUUGUC	19	8667
  BCL11A-6054	+	GGAGGCAAAAGGCGAUUGUC	20	8668
  BCL11A-7033	+	AGGAGGCAAAAGGCGAUUGUC	21	8669
  BCL11A-7034	+	GAGGAGGCAAAAGGCGAUUGUC	22	8670
  BCL11A-7035	+	CGAGGAGGCAAAAGGCGAUUGUC	23	8671
  BCL11A-7036	+	ACGAGGAGGCAAAAGGCGAUUGUC	24	8672
  BCL11A-7037	+	AGCUCUCUGGGUACUACG	18	8673
  BCL11A-7038	+	GAGCUCUCUGGGUACUACG	19	8674
  BCL11A-7039	+	UGAGCUCUCUGGGUACUACG	20	8675
  BCL11A-7040	+	UUGAGCUCUCUGGGUACUACG	21	8676
  BCL11A-7041	+	CUUGAGCUCUCUGGGUACUACG	22	8677
  BCL11A-7042	+	UCUUGAGCUCUCUGGGUACUACG	23	8678
  BCL11A-7043	+	AUCUUGAGCUCUCUGGGUACUACG	24	8679
  BCL11A-7044	+	UGAAGGGAUACCAACCCG	18	8680
  BCL11A-7045	+	CUGAAGGGAUACCAACCCG	19	8681
  BCL11A-6084	+	CCUGAAGGGAUACCAACCCG	20	8682
  BCL11A-7046	+	UCCUGAAGGGAUACCAACCCG	21	8683
  BCL11A-7047	+	GUCCUGAAGGGAUACCAACCCG	22	8684
  BCL11A-7048	+	AGUCCUGAAGGGAUACCAACCCG	23	8685
  BCL11A-7049	+	UAGUCCUGAAGGGAUACCAACCCG	24	8686
  BCL11A-7050	+	GCAAACUCCCGUUCUCCG	18	8687
  BCL11A-7051	+	CGCAAACUCCCGUUCUCCG	19	8688
  BCL11A-6094	+	GCGCAAACUCCCGUUCUCCG	20	8689
  BCL11A-7052	+	AGCGCAAACUCCCGUUCUCCG	21	8690
  BCL11A-7053	+	AAGCGCAAACUCCCGUUCUCCG	22	8691
  BCL11A-7054	+	GAAGCGCAAACUCCCGUUCUCCG	23	8692
  BCL11A-7055	+	AGAAGCGCAAACUCCCGUUCUCCG	24	8693
  BCL11A-7056	+	GGCUGGGAGGGAGGAGGG	18	8694
  BCL11A-7057	+	GGGCUGGGAGGGAGGAGGG	19	8695
  BCL11A-7058	+	GGGGCUGGGAGGGAGGAGGG	20	8696
  BCL11A-7059	+	GGGGGCUGGGAGGGAGGAGGG	21	8697
  BCL11A-7060	+	CGGGGGCUGGGAGGGAGGAGGG	22	8698
  BCL11A-7061	+	CCGGGGGCUGGGAGGGAGGAGGG	23	8699
  BCL11A-7062	+	ACCGGGGGCUGGGAGGGAGGAGGG	24	8700
  BCL11A-7063	+	UGGUGGACUAAACAGGGG	18	8701
  BCL11A-7064	+	GUGGUGGACUAAACAGGGG	19	8702
  BCL11A-6139	+	GGUGGUGGACUAAACAGGGG	20	8703
  BCL11A-7065	+	CGGUGGUGGACUAAACAGGGG	21	8704
  BCL11A-7066	+	UCGGUGGUGGACUAAACAGGGG	22	8705
  BCL11A-7067	+	CUCGGUGGUGGACUAAACAGGGG	23	8706
  BCL11A-7068	+	UCUCGGUGGUGGACUAAACAGGGG	24	8707
  BCL11A-7069	+	AAGAGAAACCAUGCACUG	18	8708
  BCL11A-7070	+	CAAGAGAAACCAUGCACUG	19	8709
  BCL11A-7071	+	GCAAGAGAAACCAUGCACUG	20	8710
  BCL11A-7072	+	UGCAAGAGAAACCAUGCACUG	21	8711
  BCL11A-7073	+	UUGCAAGAGAAACCAUGCACUG	22	8712
  BCL11A-7074	+	GUUGCAAGAGAAACCAUGCACUG	23	8713
  BCL11A-7075	+	UGUUGCAAGAGAAACCAUGCACUG	24	8714
  BCL11A-7076	+	GUCAAAGGCACUCGGGUG	18	8715
  BCL11A-7077	+	UGUCAAAGGCACUCGGGUG	19	8716
  BCL11A-7078	+	CUGUCAAAGGCACUCGGGUG	20	8717
  BCL11A-7079	+	CCUGUCAAAGGCACUCGGGUG	21	8718
  BCL11A-7080	+	CCCUGUCAAAGGCACUCGGGUG	22	8719
  BCL11A-7081	+	ACCCUGUCAAAGGCACUCGGGUG	23	8720
  BCL11A-7082	+	CACCCUGUCAAAGGCACUCGGGUG	24	8721
  BCL11A-7083	+	CCCACCAAGUCGCUGGUG	18	8722
  BCL11A-7084	+	GCCCACCAAGUCGCUGGUG	19	8723
  BCL11A-7085	+	UGCCCACCAAGUCGCUGGUG	20	8724
  BCL11A-7086	+	CUGCCCACCAAGUCGCUGGUG	21	8725
  BCL11A-7087	+	GCUGCCCACCAAGUCGCUGGUG	22	8726
  BCL11A-7088	+	CGCUGCCCACCAAGUCGCUGGUG	23	8727
  BCL11A-7089	+	GCGCUGCCCACCAAGUCGCUGGUG	24	8728
  BCL11A-7090	+	GGGGUUAUUGUCUGCAAU	18	8729
  BCL11A-7091	+	AGGGGUUAUUGUCUGCAAU	19	8730
  BCL11A-7092	+	AAGGGGUUAUUGUCUGCAAU	20	8731
  BCL11A-7093	+	AAAGGGGUUAUUGUCUGCAAU	21	8732
  BCL11A-7094	+	UAAAGGGGUUAUUGUCUGCAAU	22	8733
  BCL11A-7095	+	UUAAAGGGGUUAUUGUCUGCAAU	23	8734
  BCL11A-7096	+	GUUAAAGGGGUUAUUGUCUGCAAU	24	8735
  BCL11A-7097	+	CUGGGUACUACGCCGAAU	18	8736
  BCL11A-7098	+	UCUGGGUACUACGCCGAAU	19	8737
  BCL11A-6182	+	CUCUGGGUACUACGCCGAAU	20	8738
  BCL11A-7099	+	UCUCUGGGUACUACGCCGAAU	21	8739
  BCL11A-7100	+	CUCUCUGGGUACUACGCCGAAU	22	8740
  BCL11A-7101	+	GCUCUCUGGGUACUACGCCGAAU	23	8741
  BCL11A-7102	+	AGCUCUCUGGGUACUACGCCGAAU	24	8742
  BCL11A-7103	+	CGUAGCCGGCGAGCCACU	18	8743
  BCL11A-7104	+	GCGUAGCCGGCGAGCCACU	19	8744
  BCL11A-7105	+	CGCGUAGCCGGCGAGCCACU	20	8745
  BCL11A-7106	+	CCGCGUAGCCGGCGAGCCACU	21	8746
  BCL11A-7107	+	GCCGCGUAGCCGGCGAGCCACU	22	8747
  BCL11A-7108	+	GGCCGCGUAGCCGGCGAGCCACU	23	8748
  BCL11A-7109	+	AGGCCGCGUAGCCGGCGAGCCACU	24	8749
  BCL11A-7110	+	CCACACAUCUUGAGCUCU	18	8750
  BCL11A-7111	+	GCCACACAUCUUGAGCUCU	19	8751
  BCL11A-7112	+	UGCCACACAUCUUGAGCUCU	20	8752
  BCL11A-7113	+	CUGCCACACAUCUUGAGCUCU	21	8753
  BCL11A-7114	+	ACUGCCACACAUCUUGAGCUCU	22	8754
  BCL11A-7115	+	AACUGCCACACAUCUUGAGCUCU	23	8755
  BCL11A-7116	+	AAACUGCCACACAUCUUGAGCUCU	24	8756
  BCL11A-7117	+	CGUUCUCCGGGAUCAGGU	18	8757
  BCL11A-7118	+	CCGUUCUCCGGGAUCAGGU	19	8758
  BCL11A-6223	+	CCCGUUCUCCGGGAUCAGGU	20	8759
  BCL11A-7119	+	CCCCGUUCUCCGGGAUCAGGU	21	8760
  BCL11A-7120	+	UCCCCGUUCUCCGGGAUCAGGU	22	8761
  BCL11A-7121	+	GUCCCCGUUCUCCGGGAUCAGGU	23	8762
  BCL11A-7122	+	CGUCCCCGUUCUCCGGGAUCAGGU	24	8763
  BCL11A-7123	+	CCAGGCGCUCUAUGCGGU	18	8764
  BCL11A-7124	+	CCCAGGCGCUCUAUGCGGU	19	8765
  BCL11A-6226	+	CCCCAGGCGCUCUAUGCGGU	20	8766
  BCL11A-7125	+	CCCCCAGGCGCUCUAUGCGGU	21	8767
  BCL11A-7126	+	GCCCCCAGGCGCUCUAUGCGGU	22	8768
  BCL11A-7127	+	CGCCCCCAGGCGCUCUAUGCGGU	23	8769
  BCL11A-7128	+	CCGCCCCCAGGCGCUCUAUGCGGU	24	8770
  BCL11A-7129	-	UUCCCAGCCACCUCUCCA	18	8771
  BCL11A-7130	-	CUUCCCAGCCACCUCUCCA	19	8772
  BCL11A-5903	-	CCUUCCCAGCCACCUCUCCA	20	8773
  BCL11A-7131	-	UCCUUCCCAGCCACCUCUCCA	21	8774
  BCL11A-7132	-	GUCCUUCCCAGCCACCUCUCCA	22	8775
  BCL11A-7133	-	UGUCCUUCCCAGCCACCUCUCCA	23	8776
  BCL11A-7134	-	AUGUCCUUCCCAGCCACCUCUCCA	24	8777
  BCL11A-7135	-	AGCGCAUCAAGCUCGAGA	18	8778
  BCL11A-7136	-	AAGCGCAUCAAGCUCGAGA	19	8779
  BCL11A-5919	-	UAAGCGCAUCAAGCUCGAGA	20	8780
  BCL11A-7137	-	CUAAGCGCAUCAAGCUCGAGA	21	8781
  BCL11A-7138	-	UCUAAGCGCAUCAAGCUCGAGA	22	8782
  BCL11A-7139	-	CUCUAAGCGCAUCAAGCUCGAGA	23	8783
  BCL11A-7140	-	UCUCUAAGCGCAUCAAGCUCGAGA	24	8784
  BCL11A-7141	-	GGAGCUGACGGAGAGCGA	18	8785
  BCL11A-7142	-	AGGAGCUGACGGAGAGCGA	19	8786
  BCL11A-7143	-	GAGGAGCUGACGGAGAGCGA	20	8787
  BCL11A-7144	-	GGAGGAGCUGACGGAGAGCGA	21	8788
  BCL11A-7145	-	AGGAGGAGCUGACGGAGAGCGA	22	8789
  BCL11A-7146	-	GAGGAGGAGCUGACGGAGAGCGA	23	8790
  BCL11A-7147	-	GGAGGAGGAGCUGACGGAGAGCGA	24	8791
  BCL11A-7148	-	UCACCCGAGUGCCUUUGA	18	8792
  BCL11A-7149	-	AUCACCCGAGUGCCUUUGA	19	8793
  BCL11A-7150	-	CAUCACCCGAGUGCCUUUGA	20	8794
  BCL11A-7151	-	CCAUCACCCGAGUGCCUUUGA	21	8795
  BCL11A-7152	-	CCCAUCACCCGAGUGCCUUUGA	22	8796
  BCL11A-7153	-	ACCCAUCACCCGAGUGCCUUUGA	23	8797
  BCL11A-7154	-	CACCCAUCACCCGAGUGCCUUUGA	24	8798
  BCL11A-7155	-	GAGCACUCCUCGGAGAAC	18	8799
  BCL11A-7156	-	GGAGCACUCCUCGGAGAAC	19	8800
  BCL11A-5949	-	CGGAGCACUCCUCGGAGAAC	20	8801
  BCL11A-7157	-	UCGGAGCACUCCUCGGAGAAC	21	8802
  BCL11A-7158	-	GUCGGAGCACUCCUCGGAGAAC	22	8803
  BCL11A-7159	-	CGUCGGAGCACUCCUCGGAGAAC	23	8804
  BCL11A-7160	-	UCGUCGGAGCACUCCUCGGAGAAC	24	8805
  BCL11A-7161	-	GCCCUGGCCACCCAUCAC	18	8806
  BCL11A-7162	-	GGCCCUGGCCACCCAUCAC	19	8807
  BCL11A-7163	-	UGGCCCUGGCCACCCAUCAC	20	8808
  BCL11A-7164	-	AUGGCCCUGGCCACCCAUCAC	21	8809
  BCL11A-7165	-	GAUGGCCCUGGCCACCCAUCAC	22	8810
  BCL11A-7166	-	AGAUGGCCCUGGCCACCCAUCAC	23	8811
  BCL11A-7167	-	GAGAUGGCCCUGGCCACCCAUCAC	24	8812
  BCL11A-7168	-	UUAACCUGCUAAGAAUAC	18	8813
  BCL11A-7169	-	UUUAACCUGCUAAGAAUAC	19	8814
  BCL11A-7170	-	CUUUAACCUGCUAAGAAUAC	20	8815
  BCL11A-7171	-	CCUUUAACCUGCUAAGAAUAC	21	8816
  BCL11A-7172	-	CCCUUUAACCUGCUAAGAAUAC	22	8817
  BCL11A-7173	-	CCCCUUUAACCUGCUAAGAAUAC	23	8818
  BCL11A-7174	-	ACCCCUUUAACCUGCUAAGAAUAC	24	8819
  BCL11A-7175	-	CGGAAGUCCCCUGACCCC	18	8820
  BCL11A-7176	-	ACGGAAGUCCCCUGACCCC	19	8821
  BCL11A-7177	-	CACGGAAGUCCCCUGACCCC	20	8822
  BCL11A-7178	-	ACACGGAAGUCCCCUGACCCC	21	8823
  BCL11A-7179	-	AACACGGAAGUCCCCUGACCCC	22	8824
  BCL11A-7180	-	GAACACGGAAGUCCCCUGACCCC	23	8825
  BCL11A-7181	-	CGAACACGGAAGUCCCCUGACCCC	24	8826
  BCL11A-7182	-	AGAAAAUUUGAAGCCCCC	18	8827
  BCL11A-7183	-	GAGAAAAUUUGAAGCCCCC	19	8828
  BCL11A-5969	-	UGAGAAAAUUUGAAGCCCCC	20	8829
  BCL11A-7184	-	CUGAGAAAAUUUGAAGCCCCC	21	8830
  BCL11A-7185	-	UCUGAGAAAAUUUGAAGCCCCC	22	8831
  BCL11A-7186	-	UUCUGAGAAAAUUUGAAGCCCCC	23	8832
  BCL11A-7187	-	GUUCUGAGAAAAUUUGAAGCCCCC	24	8833
  BCL11A-7188	-	GCUAUGGAGCCUCCCGCC	18	8834
  BCL11A-7189	-	GGCUAUGGAGCCUCCCGCC	19	8835
  BCL11A-7190	-	UGGCUAUGGAGCCUCCCGCC	20	8836
  BCL11A-7191	-	AUGGCUAUGGAGCCUCCCGCC	21	8837
  BCL11A-7192	-	AAUGGCUAUGGAGCCUCCCGCC	22	8838
  BCL11A-7193	-	CAAUGGCUAUGGAGCCUCCCGCC	23	8839
  BCL11A-7194	-	CCAAUGGCUAUGGAGCCUCCCGCC	24	8840
  BCL11A-7195	-	AACACGCACAGAACACUC	18	8841
  BCL11A-7196	-	CAACACGCACAGAACACUC	19	8842
  BCL11A-7197	-	GCAACACGCACAGAACACUC	20	8843
  BCL11A-7198	-	UGCAACACGCACAGAACACUC	21	8844
  BCL11A-7199	-	UUGCAACACGCACAGAACACUC	22	8845
  BCL11A-7200	-	CUUGCAACACGCACAGAACACUC	23	8846
  BCL11A-7201	-	UCUUGCAACACGCACAGAACACUC	24	8847
  BCL11A-7202	-	ACGAAGACUCGGUGGCCG	18	8848
  BCL11A-7203	-	GACGAAGACUCGGUGGCCG	19	8849
  BCL11A-7204	-	CGACGAAGACUCGGUGGCCG	20	8850
  BCL11A-7205	-	GCGACGAAGACUCGGUGGCCG	21	8851
  BCL11A-7206	-	UGCGACGAAGACUCGGUGGCCG	22	8852
  BCL11A-7207	-	UUGCGACGAAGACUCGGUGGCCG	23	8853
  BCL11A-7208	-	CUUGCGACGAAGACUCGGUGGCCG	24	8854
  BCL11A-7209	-	GCCCGGGGAGCUGGACGG	18	8855
  BCL11A-7210	-	CGCCCGGGGAGCUGGACGG	19	8856
  BCL11A-6121	-	CCGCCCGGGGAGCUGGACGG	20	8857
  BCL11A-7211	-	ACCGCCCGGGGAGCUGGACGG	21	8858
  BCL11A-7212	-	CACCGCCCGGGGAGCUGGACGG	22	8859
  BCL11A-7213	-	ACACCGCCCGGGGAGCUGGACGG	23	8860
  BCL11A-7214	-	CACACCGCCCGGGGAGCUGGACGG	24	8861
  BCL11A-7215	-	GCCGCGGCUGCUCCCCGG	18	8862
  BCL11A-7216	-	GGCCGCGGCUGCUCCCCGG	19	8863
  BCL11A-7217	-	UGGCCGCGGCUGCUCCCCGG	20	8864
  BCL11A-7218	-	AUGGCCGCGGCUGCUCCCCGG	21	8865
  BCL11A-7219	-	AAUGGCCGCGGCUGCUCCCCGG	22	8866
  BCL11A-7220	-	UAAUGGCCGCGGCUGCUCCCCGG	23	8867
  BCL11A-7221	-	UUAAUGGCCGCGGCUGCUCCCCGG	24	8868
  BCL11A-7222	-	UUUGACAGGGUGCUGCGG	18	8869
  BCL11A-7223	-	CUUUGACAGGGUGCUGCGG	19	8870
  BCL11A-7224	-	CCUUUGACAGGGUGCUGCGG	20	8871
  BCL11A-7225	-	GCCUUUGACAGGGUGCUGCGG	21	8872
  BCL11A-7226	-	UGCCUUUGACAGGGUGCUGCGG	22	8873
  BCL11A-7227	-	GUGCCUUUGACAGGGUGCUGCGG	23	8874
  BCL11A-7228	-	AGUGCCUUUGACAGGGUGCUGCGG	24	8875
  BCL11A-7229	-	AUUUGAAGCCCCCAGGGG	18	8876
  BCL11A-7230	-	AAUUUGAAGCCCCCAGGGG	19	8877
  BCL11A-6140	-	AAAUUUGAAGCCCCCAGGGG	20	8878
  BCL11A-7231	-	AAAAUUUGAAGCCCCCAGGGG	21	8879
  BCL11A-7232	-	GAAAAUUUGAAGCCCCCAGGGG	22	8880
  BCL11A-7233	-	AGAAAAUUUGAAGCCCCCAGGGG	23	8881
  BCL11A-7234	-	GAGAAAAUUUGAAGCCCCCAGGGG	24	8882
  BCL11A-7235	-	UCCCUUCAGGACUAGGUG	18	8883
  BCL11A-7236	-	AUCCCUUCAGGACUAGGUG	19	8884
  BCL11A-7237	-	UAUCCCUUCAGGACUAGGUG	20	8885
  BCL11A-7238	-	GUAUCCCUUCAGGACUAGGUG	21	8886
  BCL11A-7239	-	GGUAUCCCUUCAGGACUAGGUG	22	8887
  BCL11A-7240	-	UGGUAUCCCUUCAGGACUAGGUG	23	8888
  BCL11A-7241	-	UUGGUAUCCCUUCAGGACUAGGUG	24	8889
  BCL11A-7242	-	CGGUCAAGUCCAAGUCAU	18	8890
  BCL11A-7243	-	CCGGUCAAGUCCAAGUCAU	19	8891
  BCL11A-7244	-	CCCGGUCAAGUCCAAGUCAU	20	8892
  BCL11A-7245	-	CCCCGGUCAAGUCCAAGUCAU	21	8893
  BCL11A-7246	-	CCCCCGGUCAAGUCCAAGUCAU	22	8894
  BCL11A-7247	-	GCCCCCGGUCAAGUCCAAGUCAU	23	8895
  BCL11A-7248	-	AGCCCCCGGUCAAGUCCAAGUCAU	24	8896
  BCL11A-7249	-	UAACCCCUUUAACCUGCU	18	8897
  BCL11A-7250	-	AUAACCCCUUUAACCUGCU	19	8898
  BCL11A-7251	-	AAUAACCCCUUUAACCUGCU	20	8899
  BCL11A-7252	-	CAAUAACCCCUUUAACCUGCU	21	8900
  BCL11A-7253	-	ACAAUAACCCCUUUAACCUGCU	22	8901
  BCL11A-7254	-	GACAAUAACCCCUUUAACCUGCU	23	8902
  BCL11A-7255	-	AGACAAUAACCCCUUUAACCUGCU	24	8903
  BCL11A-7256	-	ACAGAACACUCAUGGAUU	18	8904
  BCL11A-7257	-	CACAGAACACUCAUGGAUU	19	8905
  BCL11A-7258	-	GCACAGAACACUCAUGGAUU	20	8906
  BCL11A-7259	-	CGCACAGAACACUCAUGGAUU	21	8907
  BCL11A-7260	-	ACGCACAGAACACUCAUGGAUU	22	8908
  BCL11A-7261	-	CACGCACAGAACACUCAUGGAUU	23	8909
  BCL11A-7262	-	ACACGCACAGAACACUCAUGGAUU	24	8910
  BCL11A-7263	-	GCAGACGCAGCGACACUU	18	8911
  BCL11A-7264	-	GGCAGACGCAGCGACACUU	19	8912
  BCL11A-7265	-	GGGCAGACGCAGCGACACUU	20	8913
  BCL11A-7266	-	AGGGCAGACGCAGCGACACUU	21	8914
  BCL11A-7267	-	GAGGGCAGACGCAGCGACACUU	22	8915
  BCL11A-7268	-	AGAGGGCAGACGCAGCGACACUU	23	8916
  BCL11A-7269	-	AAGAGGGCAGACGCAGCGACACUU	24	8917
  BCL11A-7270	-	CAAGAUGUGUGGCAGUUU	18	8918
  BCL11A-7271	-	UCAAGAUGUGUGGCAGUUU	19	8919
  BCL11A-7272	-	CUCAAGAUGUGUGGCAGUUU	20	8920
  BCL11A-7273	-	GCUCAAGAUGUGUGGCAGUUU	21	8921
  BCL11A-7274	-	AGCUCAAGAUGUGUGGCAGUUU	22	8922
  BCL11A-7275	-	GAGCUCAAGAUGUGUGGCAGUUU	23	8923
  BCL11A-7276	-	AGAGCUCAAGAUGUGUGGCAGUUU	24	8924

• Table 16E 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 500 bp 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 16E
  5th Tier

  	DNA		Target Site	SEQ ID
  gRNA Name	Strand	Targeting Domain	Length	NO:

  BCL11A-7277	+	UCUCGGUGGUGGACUAAA	18	8925
  BCL11A-7278	+	GUCUCGGUGGUGGACUAAA	19	8926
  BCL11A-7279	+	UGUCUCGGUGGUGGACUAAA	20	8927
  BCL11A-7280	+	AUGUCUCGGUGGUGGACUAAA	21	8928
  BCL11A-7281	+	GAUGUCUCGGUGGUGGACUAAA	22	8929
  BCL11A-7282	+	UGAUGUCUCGGUGGUGGACUAAA	23	8930
  BCL11A-7283	+	GUGAUGUCUCGGUGGUGGACUAAA	24	8931
  BCL11A-7284	+	GUUCUGUGCGUGUUGCAA	18	8932
  BCL11A-7285	+	UGUUCUGUGCGUGUUGCAA	19	8933
  BCL11A-7286	+	GUGUUCUGUGCGUGUUGCAA	20	8934
  BCL11A-7287	+	AGUGUUCUGUGCGUGUUGCAA	21	8935
  BCL11A-7288	+	GAGUGUUCUGUGCGUGUUGCAA	22	8936
  BCL11A-7289	+	UGAGUGUUCUGUGCGUGUUGCAA	23	8937
  BCL11A-7290	+	AUGAGUGUUCUGUGCGUGUUGCAA	24	8938
  BCL11A-7291	+	UCUGGGUACUACGCCGAA	18	8939
  BCL11A-7292	+	CUCUGGGUACUACGCCGAA	19	8940
  BCL11A-5883	+	UCUCUGGGUACUACGCCGAA	20	8941
  BCL11A-7293	+	CUCUCUGGGUACUACGCCGAA	21	8942
  BCL11A-7294	+	GCUCUCUGGGUACUACGCCGAA	22	8943
  BCL11A-7295	+	AGCUCUCUGGGUACUACGCCGAA	23	8944
  BCL11A-7296	+	GAGCUCUCUGGGUACUACGCCGAA	24	8945
  BCL11A-7297	+	UCGGUGGUGGACUAAACA	18	8946
  BCL11A-7298	+	CUCGGUGGUGGACUAAACA	19	8947
  BCL11A-5892	+	UCUCGGUGGUGGACUAAACA	20	8948
  BCL11A-7299	+	GUCUCGGUGGUGGACUAAACA	21	8949
  BCL11A-7300	+	UGUCUCGGUGGUGGACUAAACA	22	8950
  BCL11A-7301	+	AUGUCUCGGUGGUGGACUAAACA	23	8951
  BCL11A-7302	+	GAUGUCUCGGUGGUGGACUAAACA	24	8952
  BCL11A-7303	+	AGAAAGAGGUUGGAGACA	18	8953
  BCL11A-7304	+	UAGAAAGAGGUUGGAGACA	19	8954
  BCL11A-7305	+	CUAGAAAGAGGUUGGAGACA	20	8955
  BCL11A-7306	+	CCUAGAAAGAGGUUGGAGACA	21	8956
  BCL11A-7307	+	ACCUAGAAAGAGGUUGGAGACA	22	8957
  BCL11A-7308	+	AACCUAGAAAGAGGUUGGAGACA	23	8958
  BCL11A-7309	+	GAACCUAGAAAGAGGUUGGAGACA	24	8959
  BCL11A-7310	+	UCUGCAAUAUGAAUCCCA	18	8960
  BCL11A-7311	+	GUCUGCAAUAUGAAUCCCA	19	8961
  BCL11A-5899	+	UGUCUGCAAUAUGAAUCCCA	20	8962
  BCL11A-7312	+	UUGUCUGCAAUAUGAAUCCCA	21	8963
  BCL11A-7313	+	AUUGUCUGCAAUAUGAAUCCCA	22	8964
  BCL11A-7314	+	UAUUGUCUGCAAUAUGAAUCCCA	23	8965
  BCL11A-7315	+	UUAUUGUCUGCAAUAUGAAUCCCA	24	8966
  BCL11A-7316	+	CCUCGCUGAAGUGCUGCA	18	8967
  BCL11A-7317	+	GCCUCGCUGAAGUGCUGCA	19	8968
  BCL11A-5909	+	GGCCUCGCUGAAGUGCUGCA	20	8969
  BCL11A-7318	+	AGGCCUCGCUGAAGUGCUGCA	21	8970
  BCL11A-7319	+	AAGGCCUCGCUGAAGUGCUGCA	22	8971
  BCL11A-7320	+	GAAGGCCUCGCUGAAGUGCUGCA	23	8972
  BCL11A-7321	+	GGAAGGCCUCGCUGAAGUGCUGCA	24	8973
  BCL11A-7322	+	GAGGAGGGGCGGAUUGCA	18	8974
  BCL11A-7323	+	GGAGGAGGGGCGGAUUGCA	19	8975
  BCL11A-7324	+	GGGAGGAGGGGCGGAUUGCA	20	8976
  BCL11A-7325	+	AGGGAGGAGGGGCGGAUUGCA	21	8977
  BCL11A-7326	+	GAGGGAGGAGGGGCGGAUUGCA	22	8978
  BCL11A-7327	+	GGAGGGAGGAGGGGCGGAUUGCA	23	8979
  BCL11A-7328	+	GGGAGGGAGGAGGGGCGGAUUGCA	24	8980
  BCL11A-7329	+	GUUGCAGUAACCUUUGCA	18	8981
  BCL11A-7330	+	GGUUGCAGUAACCUUUGCA	19	8982
  BCL11A-7331	+	UGGUUGCAGUAACCUUUGCA	20	8983
  BCL11A-7332	+	AUGGUUGCAGUAACCUUUGCA	21	8984
  BCL11A-7333	+	AAUGGUUGCAGUAACCUUUGCA	22	8985
  BCL11A-7334	+	GAAUGGUUGCAGUAACCUUUGCA	23	8986
  BCL11A-7335	+	GGAAUGGUUGCAGUAACCUUUGCA	24	8987
  BCL11A-7336	+	GCUUAGAGAAGGGGCUCA	18	8988
  BCL11A-7337	+	CGCUUAGAGAAGGGGCUCA	19	8989
  BCL11A-7338	+	GCGCUUAGAGAAGGGGCUCA	20	8990
  BCL11A-7339	+	UGCGCUUAGAGAAGGGGCUCA	21	8991
  BCL11A-7340	+	AUGCGCUUAGAGAAGGGGCUCA	22	8992
  BCL11A-7341	+	GAUGCGCUUAGAGAAGGGGCUCA	23	8993
  BCL11A-7342	+	UGAUGCGCUUAGAGAAGGGGCUCA	24	8994
  BCL11A-7343	+	CGUCGGACUUGACCGUCA	18	8995
  BCL11A-7344	+	UCGUCGGACUUGACCGUCA	19	8996
  BCL11A-5912	+	GUCGUCGGACUUGACCGUCA	20	8997
  BCL11A-7345	+	CGUCGUCGGACUUGACCGUCA	21	8998
  BCL11A-7346	+	CCGUCGUCGGACUUGACCGUCA	22	8999
  BCL11A-7347	+	ACCGUCGUCGGACUUGACCGUCA	23	9000
  BCL11A-7348	+	GACCGUCGUCGGACUUGACCGUCA	24	9001
  BCL11A-7349	+	UACCAACCCGCGGGGUCA	18	9002
  BCL11A-7350	+	AUACCAACCCGCGGGGUCA	19	9003
  BCL11A-5913	+	GAUACCAACCCGCGGGGUCA	20	9004
  BCL11A-7351	+	GGAUACCAACCCGCGGGGUCA	21	9005
  BCL11A-7352	+	GGGAUACCAACCCGCGGGGUCA	22	9006
  BCL11A-7353	+	AGGGAUACCAACCCGCGGGGUCA	23	9007
  BCL11A-7354	+	AAGGGAUACCAACCCGCGGGGUCA	24	9008
  BCL11A-7355	+	GCUUGAUGCGCUUAGAGA	18	9009
  BCL11A-7356	+	AGCUUGAUGCGCUUAGAGA	19	9010
  BCL11A-5917	+	GAGCUUGAUGCGCUUAGAGA	20	9011
  BCL11A-7357	+	CGAGCUUGAUGCGCUUAGAGA	21	9012
  BCL11A-7358	+	UCGAGCUUGAUGCGCUUAGAGA	22	9013
  BCL11A-7359	+	CUCGAGCUUGAUGCGCUUAGAGA	23	9014
  BCL11A-7360	+	UCUCGAGCUUGAUGCGCUUAGAGA	24	9015
  BCL11A-7361	+	CUAGAAAGAGGUUGGAGA	18	9016
  BCL11A-7362	+	CCUAGAAAGAGGUUGGAGA	19	9017
  BCL11A-7363	+	ACCUAGAAAGAGGUUGGAGA	20	9018
  BCL11A-7364	+	AACCUAGAAAGAGGUUGGAGA	21	9019
  BCL11A-7365	+	GAACCUAGAAAGAGGUUGGAGA	22	9020
  BCL11A-7366	+	AGAACCUAGAAAGAGGUUGGAGA	23	9021
  BCL11A-7367	+	AAGAACCUAGAAAGAGGUUGGAGA	24	9022
  BCL11A-7368	+	GUGUGUGAAGAACCUAGA	18	9023
  BCL11A-7369	+	GGUGUGUGAAGAACCUAGA	19	9024
  BCL11A-7370	+	GGGUGUGUGAAGAACCUAGA	20	9025
  BCL11A-7371	+	GGGGUGUGUGAAGAACCUAGA	21	9026
  BCL11A-7372	+	GGGGGUGUGUGAAGAACCUAGA	22	9027
  BCL11A-7373	+	UGGGGGUGUGUGAAGAACCUAGA	23	9028
  BCL11A-7374	+	AUGGGGGUGUGUGAAGAACCUAGA	24	9029
  BCL11A-7375	+	CUCUGGGUACUACGCCGA	18	9030
  BCL11A-7376	+	UCUCUGGGUACUACGCCGA	19	9031
  BCL11A-7377	+	CUCUCUGGGUACUACGCCGA	20	9032
  BCL11A-7378	+	GCUCUCUGGGUACUACGCCGA	21	9033
  BCL11A-7379	+	AGCUCUCUGGGUACUACGCCGA	22	9034
  BCL11A-7380	+	GAGCUCUCUGGGUACUACGCCGA	23	9035
  BCL11A-7381	+	UGAGCUCUCUGGGUACUACGCCGA	24	9036
  BCL11A-7382	+	GAGGUUGGAGACAGAGGA	18	9037
  BCL11A-7383	+	AGAGGUUGGAGACAGAGGA	19	9038
  BCL11A-5925	+	AAGAGGUUGGAGACAGAGGA	20	9039
  BCL11A-7384	+	AAAGAGGUUGGAGACAGAGGA	21	9040
  BCL11A-7385	+	GAAAGAGGUUGGAGACAGAGGA	22	9041
  BCL11A-7386	+	AGAAAGAGGUUGGAGACAGAGGA	23	9042
  BCL11A-7387	+	UAGAAAGAGGUUGGAGACAGAGGA	24	9043
  BCL11A-7388	+	GGGGCGGAUUGCAGAGGA	18	9044
  BCL11A-7389	+	AGGGGCGGAUUGCAGAGGA	19	9045
  BCL11A-5926	+	GAGGGGCGGAUUGCAGAGGA	20	9046
  BCL11A-7390	+	GGAGGGGCGGAUUGCAGAGGA	21	9047
  BCL11A-7391	+	AGGAGGGGCGGAUUGCAGAGGA	22	9048
  BCL11A-7392	+	GAGGAGGGGCGGAUUGCAGAGGA	23	9049
  BCL11A-7393	+	GGAGGAGGGGCGGAUUGCAGAGGA	24	9050
  BCL11A-7394	+	CGGAUUGCAGAGGAGGGA	18	9051
  BCL11A-7395	+	GCGGAUUGCAGAGGAGGGA	19	9052
  BCL11A-5930	+	GGCGGAUUGCAGAGGAGGGA	20	9053
  BCL11A-7396	+	GGGCGGAUUGCAGAGGAGGGA	21	9054
  BCL11A-7397	+	GGGGCGGAUUGCAGAGGAGGGA	22	9055
  BCL11A-7398	+	AGGGGCGGAUUGCAGAGGAGGGA	23	9056
  BCL11A-7399	+	GAGGGGCGGAUUGCAGAGGAGGGA	24	9057
  BCL11A-7400	+	CUUGACCGGGGGCUGGGA	18	9058
  BCL11A-7401	+	ACUUGACCGGGGGCUGGGA	19	9059
  BCL11A-5931	+	GACUUGACCGGGGGCUGGGA	20	9060
  BCL11A-7402	+	GGACUUGACCGGGGGCUGGGA	21	9061
  BCL11A-7403	+	UGGACUUGACCGGGGGCUGGGA	22	9062
  BCL11A-7404	+	UUGGACUUGACCGGGGGCUGGGA	23	9063
  BCL11A-7405	+	CUUGGACUUGACCGGGGGCUGGGA	24	9064
  BCL11A-7406	+	CGCAUGACUUGGACUUGA	18	9065
  BCL11A-7407	+	UCGCAUGACUUGGACUUGA	19	9066
  BCL11A-7408	+	CUCGCAUGACUUGGACUUGA	20	9067
  BCL11A-7409	+	ACUCGCAUGACUUGGACUUGA	21	9068
  BCL11A-7410	+	AACUCGCAUGACUUGGACUUGA	22	9069
  BCL11A-7411	+	GAACUCGCAUGACUUGGACUUGA	23	9070
  BCL11A-7412	+	AGAACUCGCAUGACUUGGACUUGA	24	9071
  BCL11A-7413	+	GGGCCCGGACCACUAAUA	18	9072
  BCL11A-7414	+	CGGGCCCGGACCACUAAUA	19	9073
  BCL11A-5940	+	CCGGGCCCGGACCACUAAUA	20	9074
  BCL11A-7415	+	CCCGGGCCCGGACCACUAAUA	21	9075
  BCL11A-7416	+	GCCCGGGCCCGGACCACUAAUA	22	9076
  BCL11A-7417	+	UGCCCGGGCCCGGACCACUAAUA	23	9077
  BCL11A-7418	+	CUGCCCGGGCCCGGACCACUAAUA	24	9078
  BCL11A-7419	+	AGCUCUCUAAGUCUCCUA	18	9079
  BCL11A-7420	+	CAGCUCUCUAAGUCUCCUA	19	9080
  BCL11A-7421	+	CCAGCUCUCUAAGUCUCCUA	20	9081
  BCL11A-7422	+	GCCAGCUCUCUAAGUCUCCUA	21	9082
  BCL11A-7423	+	UGCCAGCUCUCUAAGUCUCCUA	22	9083
  BCL11A-7424	+	CUGCCAGCUCUCUAAGUCUCCUA	23	9084
  BCL11A-7425	+	CCUGCCAGCUCUCUAAGUCUCCUA	24	9085
  BCL11A-7426	+	CUGGAGUCUCCGAAGCUA	18	9086
  BCL11A-7427	+	UCUGGAGUCUCCGAAGCUA	19	9087
  BCL11A-5943	+	GUCUGGAGUCUCCGAAGCUA	20	9088
  BCL11A-7428	+	UGUCUGGAGUCUCCGAAGCUA	21	9089
  BCL11A-7429	+	UUGUCUGGAGUCUCCGAAGCUA	22	9090
  BCL11A-7430	+	AUUGUCUGGAGUCUCCGAAGCUA	23	9091
  BCL11A-7431	+	GAUUGUCUGGAGUCUCCGAAGCUA	24	9092
  BCL11A-7432	+	UCGAGCUUGAUGCGCUUA	18	9093
  BCL11A-7433	+	CUCGAGCUUGAUGCGCUUA	19	9094
  BCL11A-7434	+	UCUCGAGCUUGAUGCGCUUA	20	9095
  BCL11A-7435	+	UUCUCGAGCUUGAUGCGCUUA	21	9096
  BCL11A-7436	+	CUUCUCGAGCUUGAUGCGCUUA	22	9097
  BCL11A-7437	+	CCUUCUCGAGCUUGAUGCGCUUA	23	9098
  BCL11A-7438	+	UCCUUCUCGAGCUUGAUGCGCUUA	24	9099
  BCL11A-7439	+	GGUAUUCUUAGCAGGUUA	18	9100
  BCL11A-7440	+	UGGUAUUCUUAGCAGGUUA	19	9101
  BCL11A-7441	+	CUGGUAUUCUUAGCAGGUUA	20	9102
  BCL11A-7442	+	CCUGGUAUUCUUAGCAGGUUA	21	9103
  BCL11A-7443	+	UCCUGGUAUUCUUAGCAGGUUA	22	9104
  BCL11A-7444	+	AUCCUGGUAUUCUUAGCAGGUUA	23	9105
  BCL11A-7445	+	GAUCCUGGUAUUCUUAGCAGGUUA	24	9106
  BCL11A-7446	+	CUCGGUGGUGGACUAAAC	18	9107
  BCL11A-7447	+	UCUCGGUGGUGGACUAAAC	19	9108
  BCL11A-5947	+	GUCUCGGUGGUGGACUAAAC	20	9109
  BCL11A-7448	+	UGUCUCGGUGGUGGACUAAAC	21	9110
  BCL11A-7449	+	AUGUCUCGGUGGUGGACUAAAC	22	9111
  BCL11A-7450	+	GAUGUCUCGGUGGUGGACUAAAC	23	9112
  BCL11A-7451	+	UGAUGUCUCGGUGGUGGACUAAAC	24	9113
  BCL11A-7452	+	UCCGAGGAGUGCUCCGAC	18	9114
  BCL11A-7453	+	CUCCGAGGAGUGCUCCGAC	19	9115
  BCL11A-7454	+	UCUCCGAGGAGUGCUCCGAC	20	9116
  BCL11A-7455	+	UUCUCCGAGGAGUGCUCCGAC	21	9117
  BCL11A-7456	+	GUUCUCCGAGGAGUGCUCCGAC	22	9118
  BCL11A-7457	+	CGUUCUCCGAGGAGUGCUCCGAC	23	9119
  BCL11A-7458	+	CCGUUCUCCGAGGAGUGCUCCGAC	24	9120
  BCL11A-7459	+	AACUUGGCCACCACGGAC	18	9121
  BCL11A-7460	+	GAACUUGGCCACCACGGAC	19	9122
  BCL11A-7461	+	UGAACUUGGCCACCACGGAC	20	9123
  BCL11A-7462	+	UUGAACUUGGCCACCACGGAC	21	9124
  BCL11A-7463	+	CUUGAACUUGGCCACCACGGAC	22	9125
  BCL11A-7464	+	UCUUGAACUUGGCCACCACGGAC	23	9126
  BCL11A-7465	+	CUCUUGAACUUGGCCACCACGGAC	24	9127
  BCL11A-7466	+	CCGCAGAACUCGCAUGAC	18	9128
  BCL11A-7467	+	GCCGCAGAACUCGCAUGAC	19	9129
  BCL11A-7468	+	UGCCGCAGAACUCGCAUGAC	20	9130
  BCL11A-7469	+	UUGCCGCAGAACUCGCAUGAC	21	9131
  BCL11A-7470	+	CUUGCCGCAGAACUCGCAUGAC	22	9132
  BCL11A-7471	+	UCUUGCCGCAGAACUCGCAUGAC	23	9133
  BCL11A-7472	+	GUCUUGCCGCAGAACUCGCAUGAC	24	9134
  BCL11A-7473	+	GCAUGACUUGGACUUGAC	18	9135
  BCL11A-7474	+	CGCAUGACUUGGACUUGAC	19	9136
  BCL11A-5957	+	UCGCAUGACUUGGACUUGAC	20	9137
  BCL11A-7475	+	CUCGCAUGACUUGGACUUGAC	21	9138
  BCL11A-7476	+	ACUCGCAUGACUUGGACUUGAC	22	9139
  BCL11A-7477	+	AACUCGCAUGACUUGGACUUGAC	23	9140
  BCL11A-7478	+	GAACUCGCAUGACUUGGACUUGAC	24	9141
  BCL11A-7479	+	GGGGGUGUGUGAAGAACC	18	9142
  BCL11A-7480	+	UGGGGGUGUGUGAAGAACC	19	9143
  BCL11A-7481	+	AUGGGGGUGUGUGAAGAACC	20	9144
  BCL11A-7482	+	AAUGGGGGUGUGUGAAGAACC	21	9145
  BCL11A-7483	+	GAAUGGGGGUGUGUGAAGAACC	22	9146
  BCL11A-7484	+	CGAAUGGGGGUGUGUGAAGAACC	23	9147
  BCL11A-7485	+	CCGAAUGGGGGUGUGUGAAGAACC	24	9148
  BCL11A-7486	+	CUCUUGAACUUGGCCACC	18	9149
  BCL11A-7487	+	GCUCUUGAACUUGGCCACC	19	9150
  BCL11A-7488	+	CGCUCUUGAACUUGGCCACC	20	9151
  BCL11A-7489	+	UCGCUCUUGAACUUGGCCACC	21	9152
  BCL11A-7490	+	CUCGCUCUUGAACUUGGCCACC	22	9153
  BCL11A-7491	+	UCUCGCUCUUGAACUUGGCCACC	23	9154
  BCL11A-7492	+	UUCUCGCUCUUGAACUUGGCCACC	24	9155
  BCL11A-7493	+	CAUGACUUGGACUUGACC	18	9156
  BCL11A-7494	+	GCAUGACUUGGACUUGACC	19	9157
  BCL11A-5965	+	CGCAUGACUUGGACUUGACC	20	9158
  BCL11A-7495	+	UCGCAUGACUUGGACUUGACC	21	9159
  BCL11A-7496	+	CUCGCAUGACUUGGACUUGACC	22	9160
  BCL11A-7497	+	ACUCGCAUGACUUGGACUUGACC	23	9161
  BCL11A-7498	+	AACUCGCAUGACUUGGACUUGACC	24	9162
  BCL11A-7499	+	CUGAAGGGAUACCAACCC	18	9163
  BCL11A-7500	+	CCUGAAGGGAUACCAACCC	19	9164
  BCL11A-7501	+	UCCUGAAGGGAUACCAACCC	20	9165
  BCL11A-7502	+	GUCCUGAAGGGAUACCAACCC	21	9166
  BCL11A-7503	+	AGUCCUGAAGGGAUACCAACCC	22	9167
  BCL11A-7504	+	UAGUCCUGAAGGGAUACCAACCC	23	9168
  BCL11A-7505	+	CUAGUCCUGAAGGGAUACCAACCC	24	9169
  BCL11A-7506	+	CGCCCACGACCGCGCCCC	18	9170
  BCL11A-7507	+	ACGCCCACGACCGCGCCCC	19	9171
  BCL11A-3830	+	CACGCCCACGACCGCGCCCC	20	9172
  BCL11A-7508	+	CCACGCCCACGACCGCGCCCC	21	9173
  BCL11A-7509	+	CCCACGCCCACGACCGCGCCCC	22	9174
  BCL11A-7510	+	GCCCACGCCCACGACCGCGCCCC	23	9175
  BCL11A-7511	+	CGCCCACGCCCACGACCGCGCCCC	24	9176
  BCL11A-7512	+	GCUUUUUGGACAGGCCCC	18	9177
  BCL11A-7513	+	AGCUUUUUGGACAGGCCCC	19	9178
  BCL11A-7514	+	CAGCUUUUUGGACAGGCCCC	20	9179
  BCL11A-7515	+	GCAGCUUUUUGGACAGGCCCC	21	9180
  BCL11A-7516	+	AGCAGCUUUUUGGACAGGCCCC	22	9181
  BCL11A-7517	+	CAGCAGCUUUUUGGACAGGCCCC	23	9182
  BCL11A-7518	+	GCAGCAGCUUUUUGGACAGGCCCC	24	9183
  BCL11A-7519	+	CCCGAGGCCGACUCGCCC	18	9184
  BCL11A-7520	+	CCCCGAGGCCGACUCGCCC	19	9185
  BCL11A-5977	+	CCCCCGAGGCCGACUCGCCC	20	9186
  BCL11A-7521	+	CCCCCCGAGGCCGACUCGCCC	21	9187
  BCL11A-7522	+	GCCCCCCGAGGCCGACUCGCCC	22	9188
  BCL11A-7523	+	GGCCCCCCGAGGCCGACUCGCCC	23	9189
  BCL11A-7524	+	AGGCCCCCCGAGGCCGACUCGCCC	24	9190
  BCL11A-7525	+	GUCUGCAAUAUGAAUCCC	18	9191
  BCL11A-7526	+	UGUCUGCAAUAUGAAUCCC	19	9192
  BCL11A-7527	+	UUGUCUGCAAUAUGAAUCCC	20	9193
  BCL11A-7528	+	AUUGUCUGCAAUAUGAAUCCC	21	9194
  BCL11A-7529	+	UAUUGUCUGCAAUAUGAAUCCC	22	9195
  BCL11A-7530	+	UUAUUGUCUGCAAUAUGAAUCCC	23	9196
  BCL11A-7531	+	GUUAUUGUCUGCAAUAUGAAUCCC	24	9197
  BCL11A-7532	+	UUCCCGUGCCGCUGCGCC	18	9198
  BCL11A-7533	+	CUUCCCGUGCCGCUGCGCC	19	9199
  BCL11A-7534	+	ACUUCCCGUGCCGCUGCGCC	20	9200
  BCL11A-7535	+	CACUUCCCGUGCCGCUGCGCC	21	9201
  BCL11A-7536	+	CCACUUCCCGUGCCGCUGCGCC	22	9202
  BCL11A-7537	+	UCCACUUCCCGUGCCGCUGCGCC	23	9203
  BCL11A-7538	+	CUCCACUUCCCGUGCCGCUGCGCC	24	9204
  BCL11A-7539	+	CCCCGAGGCCGACUCGCC	18	9205
  BCL11A-7540	+	CCCCCGAGGCCGACUCGCC	19	9206
  BCL11A-5989	+	CCCCCCGAGGCCGACUCGCC	20	9207
  BCL11A-7541	+	GCCCCCCGAGGCCGACUCGCC	21	9208
  BCL11A-7542	+	GGCCCCCCGAGGCCGACUCGCC	22	9209
  BCL11A-7543	+	AGGCCCCCCGAGGCCGACUCGCC	23	9210
  BCL11A-7544	+	CAGGCCCCCCGAGGCCGACUCGCC	24	9211
  BCL11A-7545	+	GCGCUUAUGCUUCUCGCC	18	9212
  BCL11A-7546	+	CGCGCUUAUGCUUCUCGCC	19	9213
  BCL11A-7547	+	CCGCGCUUAUGCUUCUCGCC	20	9214
  BCL11A-7548	+	GCCGCGCUUAUGCUUCUCGCC	21	9215
  BCL11A-7549	+	GGCCGCGCUUAUGCUUCUCGCC	22	9216
  BCL11A-7550	+	UGGCCGCGCUUAUGCUUCUCGCC	23	9217
  BCL11A-7551	+	GUGGCCGCGCUUAUGCUUCUCGCC	24	9218
  BCL11A-7552	+	GGGAGGGGGGGCGUCGCC	18	9219
  BCL11A-7553	+	AGGGAGGGGGGGCGUCGCC	19	9220
  BCL11A-5990	+	GAGGGAGGGGGGGCGUCGCC	20	9221
  BCL11A-7554	+	GGAGGGAGGGGGGGCGUCGCC	21	9222
  BCL11A-7555	+	AGGAGGGAGGGGGGGCGUCGCC	22	9223
  BCL11A-7556	+	GAGGAGGGAGGGGGGGCGUCGCC	23	9224
  BCL11A-7557	+	AGAGGAGGGAGGGGGGGCGUCGCC	24	9225
  BCL11A-7558	+	CAUAGGGCUGGGCCGGCC	18	9226
  BCL11A-7559	+	GCAUAGGGCUGGGCCGGCC	19	9227
  BCL11A-5991	+	UGCAUAGGGCUGGGCCGGCC	20	9228
  BCL11A-7560	+	UUGCAUAGGGCUGGGCCGGCC	21	9229
  BCL11A-7561	+	UUUGCAUAGGGCUGGGCCGGCC	22	9230
  BCL11A-7562	+	CUUUGCAUAGGGCUGGGCCGGCC	23	9231
  BCL11A-7563	+	CCUUUGCAUAGGGCUGGGCCGGCC	24	9232
  BCL11A-7564	+	GUGUUGGGCAUCGCGGCC	18	9233
  BCL11A-7565	+	CGUGUUGGGCAUCGCGGCC	19	9234
  BCL11A-5993	+	CCGUGUUGGGCAUCGCGGCC	20	9235
  BCL11A-7566	+	UCCGUGUUGGGCAUCGCGGCC	21	9236
  BCL11A-7567	+	CUCCGUGUUGGGCAUCGCGGCC	22	9237
  BCL11A-7568	+	UCUCCGUGUUGGGCAUCGCGGCC	23	9238
  BCL11A-7569	+	UUCUCCGUGUUGGGCAUCGCGGCC	24	9239
  BCL11A-7570	+	AGGGAUCUUUGAGCUGCC	18	9240
  BCL11A-7571	+	AAGGGAUCUUUGAGCUGCC	19	9241
  BCL11A-6000	+	GAAGGGAUCUUUGAGCUGCC	20	9242
  BCL11A-7572	+	GGAAGGGAUCUUUGAGCUGCC	21	9243
  BCL11A-7573	+	AGGAAGGGAUCUUUGAGCUGCC	22	9244
  BCL11A-7574	+	AAGGAAGGGAUCUUUGAGCUGCC	23	9245
  BCL11A-7575	+	UAAGGAAGGGAUCUUUGAGCUGCC	24	9246
  BCL11A-7576	+	AUCCCUCCGUCCAGCUCC	18	9247
  BCL11A-7577	+	GAUCCCUCCGUCCAGCUCC	19	9248
  BCL11A-7578	+	AGAUCCCUCCGUCCAGCUCC	20	9249
  BCL11A-7579	+	GAGAUCCCUCCGUCCAGCUCC	21	9250
  BCL11A-7580	+	CGAGAUCCCUCCGUCCAGCUCC	22	9251
  BCL11A-7581	+	CCGAGAUCCCUCCGUCCAGCUCC	23	9252
  BCL11A-7582	+	CCCGAGAUCCCUCCGUCCAGCUCC	24	9253
  BCL11A-7583	+	CCAGCUCUCUAAGUCUCC	18	9254
  BCL11A-7584	+	GCCAGCUCUCUAAGUCUCC	19	9255
  BCL11A-7585	+	UGCCAGCUCUCUAAGUCUCC	20	9256
  BCL11A-7586	+	CUGCCAGCUCUCUAAGUCUCC	21	9257
  BCL11A-7587	+	CCUGCCAGCUCUCUAAGUCUCC	22	9258
  BCL11A-7588	+	CCCUGCCAGCUCUCUAAGUCUCC	23	9259
  BCL11A-7589	+	UCCCUGCCAGCUCUCUAAGUCUCC	24	9260
  BCL11A-7590	+	CGCAAACUCCCGUUCUCC	18	9261
  BCL11A-7591	+	GCGCAAACUCCCGUUCUCC	19	9262
  BCL11A-7592	+	AGCGCAAACUCCCGUUCUCC	20	9263
  BCL11A-7593	+	AAGCGCAAACUCCCGUUCUCC	21	9264
  BCL11A-7594	+	GAAGCGCAAACUCCCGUUCUCC	22	9265
  BCL11A-7595	+	AGAAGCGCAAACUCCCGUUCUCC	23	9266
  BCL11A-7596	+	GAGAAGCGCAAACUCCCGUUCUCC	24	9267
  BCL11A-7597	+	UCGCUGGUGCCGGGUUCC	18	9268
  BCL11A-7598	+	GUCGCUGGUGCCGGGUUCC	19	9269
  BCL11A-6011	+	AGUCGCUGGUGCCGGGUUCC	20	9270
  BCL11A-7599	+	AAGUCGCUGGUGCCGGGUUCC	21	9271
  BCL11A-7600	+	CAAGUCGCUGGUGCCGGGUUCC	22	9272
  BCL11A-7601	+	CCAAGUCGCUGGUGCCGGGUUCC	23	9273
  BCL11A-7602	+	ACCAAGUCGCUGGUGCCGGGUUCC	24	9274
  BCL11A-7603	+	GCCGCCUCCAGGCUCAGC	18	9275
  BCL11A-7604	+	CGCCGCCUCCAGGCUCAGC	19	9276
  BCL11A-7605	+	GCGCCGCCUCCAGGCUCAGC	20	9277
  BCL11A-7606	+	CGCGCCGCCUCCAGGCUCAGC	21	9278
  BCL11A-7607	+	GCGCGCCGCCUCCAGGCUCAGC	22	9279
  BCL11A-7608	+	GGCGCGCCGCCUCCAGGCUCAGC	23	9280
  BCL11A-7609	+	UGGCGCGCCGCCUCCAGGCUCAGC	24	9281
  BCL11A-7610	+	AGAAGGGGCUCAGCGAGC	18	9282
  BCL11A-7611	+	GAGAAGGGGCUCAGCGAGC	19	9283
  BCL11A-6013	+	AGAGAAGGGGCUCAGCGAGC	20	9284
  BCL11A-7612	+	UAGAGAAGGGGCUCAGCGAGC	21	9285
  BCL11A-7613	+	UUAGAGAAGGGGCUCAGCGAGC	22	9286
  BCL11A-7614	+	CUUAGAGAAGGGGCUCAGCGAGC	23	9287
  BCL11A-7615	+	GCUUAGAGAAGGGGCUCAGCGAGC	24	9288
  BCL11A-7616	+	CCCCCGAGGCCGACUCGC	18	9289
  BCL11A-7617	+	CCCCCCGAGGCCGACUCGC	19	9290
  BCL11A-7618	+	GCCCCCCGAGGCCGACUCGC	20	9291
  BCL11A-7619	+	GGCCCCCCGAGGCCGACUCGC	21	9292
  BCL11A-7620	+	AGGCCCCCCGAGGCCGACUCGC	22	9293
  BCL11A-7621	+	CAGGCCCCCCGAGGCCGACUCGC	23	9294
  BCL11A-7622	+	ACAGGCCCCCCGAGGCCGACUCGC	24	9295
  BCL11A-7623	+	AGGGAGGGGGGGCGUCGC	18	9296
  BCL11A-7624	+	GAGGGAGGGGGGGCGUCGC	19	9297
  BCL11A-7625	+	GGAGGGAGGGGGGGCGUCGC	20	9298
  BCL11A-7626	+	AGGAGGGAGGGGGGGCGUCGC	21	9299
  BCL11A-7627	+	GAGGAGGGAGGGGGGGCGUCGC	22	9300
  BCL11A-7628	+	AGAGGAGGGAGGGGGGGCGUCGC	23	9301
  BCL11A-7629	+	CAGAGGAGGGAGGGGGGGCGUCGC	24	9302
  BCL11A-7630	+	AGCGCCCUUCUGCCAGGC	18	9303
  BCL11A-7631	+	AAGCGCCCUUCUGCCAGGC	19	9304
  BCL11A-6027	+	AAAGCGCCCUUCUGCCAGGC	20	9305
  BCL11A-7632	+	GAAAGCGCCCUUCUGCCAGGC	21	9306
  BCL11A-7633	+	GGAAAGCGCCCUUCUGCCAGGC	22	9307
  BCL11A-7634	+	UGGAAAGCGCCCUUCUGCCAGGC	23	9308
  BCL11A-7635	+	GUGGAAAGCGCCCUUCUGCCAGGC	24	9309
  BCL11A-7636	+	GCAUAGGGCUGGGCCGGC	18	9310
  BCL11A-7637	+	UGCAUAGGGCUGGGCCGGC	19	9311
  BCL11A-7638	+	UUGCAUAGGGCUGGGCCGGC	20	9312
  BCL11A-7639	+	UUUGCAUAGGGCUGGGCCGGC	21	9313
  BCL11A-7640	+	CUUUGCAUAGGGCUGGGCCGGC	22	9314
  BCL11A-7641	+	CCUUUGCAUAGGGCUGGGCCGGC	23	9315
  BCL11A-7642	+	ACCUUUGCAUAGGGCUGGGCCGGC	24	9316
  BCL11A-7643	+	CGUGUUGGGCAUCGCGGC	18	9317
  BCL11A-7644	+	CCGUGUUGGGCAUCGCGGC	19	9318
  BCL11A-6028	+	UCCGUGUUGGGCAUCGCGGC	20	9319
  BCL11A-7645	+	CUCCGUGUUGGGCAUCGCGGC	21	9320
  BCL11A-7646	+	UCUCCGUGUUGGGCAUCGCGGC	22	9321
  BCL11A-7647	+	UUCUCCGUGUUGGGCAUCGCGGC	23	9322
  BCL11A-7648	+	GUUCUCCGUGUUGGGCAUCGCGGC	24	9323
  BCL11A-7649	+	AGCUGGGCCUGCCCGGGC	18	9324
  BCL11A-7650	+	GAGCUGGGCCUGCCCGGGC	19	9325
  BCL11A-7651	+	UGAGCUGGGCCUGCCCGGGC	20	9326
  BCL11A-7652	+	UUGAGCUGGGCCUGCCCGGGC	21	9327
  BCL11A-7653	+	UUUGAGCUGGGCCUGCCCGGGC	22	9328
  BCL11A-7654	+	UUUUGAGCUGGGCCUGCCCGGGC	23	9329
  BCL11A-7655	+	CUUUUGAGCUGGGCCUGCCCGGGC	24	9330
  BCL11A-7656	+	UUGGACUUGACCGGGGGC	18	9331
  BCL11A-7657	+	CUUGGACUUGACCGGGGGC	19	9332
  BCL11A-6032	+	ACUUGGACUUGACCGGGGGC	20	9333
  BCL11A-7658	+	GACUUGGACUUGACCGGGGGC	21	9334
  BCL11A-7659	+	UGACUUGGACUUGACCGGGGGC	22	9335
  BCL11A-7660	+	AUGACUUGGACUUGACCGGGGGC	23	9336
  BCL11A-7661	+	CAUGACUUGGACUUGACCGGGGGC	24	9337
  BCL11A-7662	+	CCUAGAGAAAUCCAUGGC	18	9338
  BCL11A-7663	+	UCCUAGAGAAAUCCAUGGC	19	9339
  BCL11A-6035	+	CUCCUAGAGAAAUCCAUGGC	20	9340
  BCL11A-7664	+	UCUCCUAGAGAAAUCCAUGGC	21	9341
  BCL11A-7665	+	GUCUCCUAGAGAAAUCCAUGGC	22	9342
  BCL11A-7666	+	AGUCUCCUAGAGAAAUCCAUGGC	23	9343
  BCL11A-7667	+	AAGUCUCCUAGAGAAAUCCAUGGC	24	9344
  BCL11A-7668	+	AUCCCAUGGAGAGGUGGC	18	9345
  BCL11A-7669	+	AAUCCCAUGGAGAGGUGGC	19	9346
  BCL11A-6038	+	GAAUCCCAUGGAGAGGUGGC	20	9347
  BCL11A-7670	+	UGAAUCCCAUGGAGAGGUGGC	21	9348
  BCL11A-7671	+	AUGAAUCCCAUGGAGAGGUGGC	22	9349
  BCL11A-7672	+	UAUGAAUCCCAUGGAGAGGUGGC	23	9350
  BCL11A-7673	+	AUAUGAAUCCCAUGGAGAGGUGGC	24	9351
  BCL11A-7674	+	ACUCGGGUGAUGGGUGGC	18	9352
  BCL11A-7675	+	CACUCGGGUGAUGGGUGGC	19	9353
  BCL11A-7676	+	GCACUCGGGUGAUGGGUGGC	20	9354
  BCL11A-7677	+	GGCACUCGGGUGAUGGGUGGC	21	9355
  BCL11A-7678	+	AGGCACUCGGGUGAUGGGUGGC	22	9356
  BCL11A-7679	+	AAGGCACUCGGGUGAUGGGUGGC	23	9357
  BCL11A-7680	+	AAAGGCACUCGGGUGAUGGGUGGC	24	9358
  BCL11A-7681	+	CUUUUGAGCUGGGCCUGC	18	9359
  BCL11A-7682	+	UCUUUUGAGCUGGGCCUGC	19	9360
  BCL11A-7683	+	CUCUUUUGAGCUGGGCCUGC	20	9361
  BCL11A-7684	+	CCUCUUUUGAGCUGGGCCUGC	21	9362
  BCL11A-7685	+	CCCUCUUUUGAGCUGGGCCUGC	22	9363
  BCL11A-7686	+	GCCCUCUUUUGAGCUGGGCCUGC	23	9364
  BCL11A-7687	+	UGCCCUCUUUUGAGCUGGGCCUGC	24	9365
  BCL11A-7688	+	AAGGGAUCUUUGAGCUGC	18	9366
  BCL11A-7689	+	GAAGGGAUCUUUGAGCUGC	19	9367
  BCL11A-7690	+	GGAAGGGAUCUUUGAGCUGC	20	9368
  BCL11A-7691	+	AGGAAGGGAUCUUUGAGCUGC	21	9369
  BCL11A-7692	+	AAGGAAGGGAUCUUUGAGCUGC	22	9370
  BCL11A-7693	+	UAAGGAAGGGAUCUUUGAGCUGC	23	9371
  BCL11A-7694	+	CUAAGGAAGGGAUCUUUGAGCUGC	24	9372
  BCL11A-7695	+	GCCUCGCUGAAGUGCUGC	18	9373
  BCL11A-7696	+	GGCCUCGCUGAAGUGCUGC	19	9374
  BCL11A-7697	+	AGGCCUCGCUGAAGUGCUGC	20	9375
  BCL11A-7698	+	AAGGCCUCGCUGAAGUGCUGC	21	9376
  BCL11A-7699	+	GAAGGCCUCGCUGAAGUGCUGC	22	9377
  BCL11A-7700	+	GGAAGGCCUCGCUGAAGUGCUGC	23	9378
  BCL11A-7701	+	UGGAAGGCCUCGCUGAAGUGCUGC	24	9379
  BCL11A-7702	+	GUGUUCUGUGCGUGUUGC	18	9380
  BCL11A-7703	+	AGUGUUCUGUGCGUGUUGC	19	9381
  BCL11A-7704	+	GAGUGUUCUGUGCGUGUUGC	20	9382
  BCL11A-7705	+	UGAGUGUUCUGUGCGUGUUGC	21	9383
  BCL11A-7706	+	AUGAGUGUUCUGUGCGUGUUGC	22	9384
  BCL11A-7707	+	CAUGAGUGUUCUGUGCGUGUUGC	23	9385
  BCL11A-7708	+	CCAUGAGUGUUCUGUGCGUGUUGC	24	9386
  BCL11A-7709	+	CGAAAACUGCCACACAUC	18	9387
  BCL11A-7710	+	CCGAAAACUGCCACACAUC	19	9388
  BCL11A-7711	+	UCCGAAAACUGCCACACAUC	20	9389
  BCL11A-7712	+	AUCCGAAAACUGCCACACAUC	21	9390
  BCL11A-7713	+	CAUCCGAAAACUGCCACACAUC	22	9391
  BCL11A-7714	+	CCAUCCGAAAACUGCCACACAUC	23	9392
  BCL11A-7715	+	UCCAUCCGAAAACUGCCACACAUC	24	9393
  BCL11A-7716	+	UUGGGGUCGUUCUCGCUC	18	9394
  BCL11A-7717	+	GUUGGGGUCGUUCUCGCUC	19	9395
  BCL11A-7718	+	GGUUGGGGUCGUUCUCGCUC	20	9396
  BCL11A-7719	+	AGGUUGGGGUCGUUCUCGCUC	21	9397
  BCL11A-7720	+	CAGGUUGGGGUCGUUCUCGCUC	22	9398
  BCL11A-7721	+	UCAGGUUGGGGUCGUUCUCGCUC	23	9399
  BCL11A-7722	+	AUCAGGUUGGGGUCGUUCUCGCUC	24	9400
  BCL11A-7723	+	CUCAGAACUUAAGGGCUC	18	9401
  BCL11A-7724	+	UCUCAGAACUUAAGGGCUC	19	9402
  BCL11A-7725	+	UUCUCAGAACUUAAGGGCUC	20	9403
  BCL11A-7726	+	UUUCUCAGAACUUAAGGGCUC	21	9404
  BCL11A-7727	+	UUUUCUCAGAACUUAAGGGCUC	22	9405
  BCL11A-7728	+	AUUUUCUCAGAACUUAAGGGCUC	23	9406
  BCL11A-7729	+	AAUUUUCUCAGAACUUAAGGGCUC	24	9407
  BCL11A-7730	+	GACAUUCUGCACCUAGUC	18	9408
  BCL11A-7731	+	GGACAUUCUGCACCUAGUC	19	9409
  BCL11A-7732	+	AGGACAUUCUGCACCUAGUC	20	9410
  BCL11A-7733	+	AAGGACAUUCUGCACCUAGUC	21	9411
  BCL11A-7734	+	GAAGGACAUUCUGCACCUAGUC	22	9412
  BCL11A-7735	+	GGAAGGACAUUCUGCACCUAGUC	23	9413
  BCL11A-7736	+	GGGAAGGACAUUCUGCACCUAGUC	24	9414
  BCL11A-7737	+	UCGUCGGACUUGACCGUC	18	9415
  BCL11A-7738	+	GUCGUCGGACUUGACCGUC	19	9416
  BCL11A-7739	+	CGUCGUCGGACUUGACCGUC	20	9417
  BCL11A-7740	+	CCGUCGUCGGACUUGACCGUC	21	9418
  BCL11A-7741	+	ACCGUCGUCGGACUUGACCGUC	22	9419
  BCL11A-7742	+	GACCGUCGUCGGACUUGACCGUC	23	9420
  BCL11A-7743	+	AGACCGUCGUCGGACUUGACCGUC	24	9421
  BCL11A-7744	+	AUACCAACCCGCGGGGUC	18	9422
  BCL11A-7745	+	GAUACCAACCCGCGGGGUC	19	9423
  BCL11A-6052	+	GGAUACCAACCCGCGGGGUC	20	9424
  BCL11A-7746	+	GGGAUACCAACCCGCGGGGUC	21	9425
  BCL11A-7747	+	AGGGAUACCAACCCGCGGGGUC	22	9426
  BCL11A-7748	+	AAGGGAUACCAACCCGCGGGGUC	23	9427
  BCL11A-7749	+	GAAGGGAUACCAACCCGCGGGGUC	24	9428
  BCL11A-7750	+	GGCAGGUCGAACUCCUUC	18	9429
  BCL11A-7751	+	GGGCAGGUCGAACUCCUUC	19	9430
  BCL11A-7752	+	GGGGCAGGUCGAACUCCUUC	20	9431
  BCL11A-7753	+	GGGGGCAGGUCGAACUCCUUC	21	9432
  BCL11A-7754	+	CGGGGGCAGGUCGAACUCCUUC	22	9433
  BCL11A-7755	+	CCGGGGGCAGGUCGAACUCCUUC	23	9434
  BCL11A-7756	+	GCCGGGGGCAGGUCGAACUCCUUC	24	9435
  BCL11A-7757	+	GUCGCUGGUGCCGGGUUC	18	9436
  BCL11A-7758	+	AGUCGCUGGUGCCGGGUUC	19	9437
  BCL11A-6058	+	AAGUCGCUGGUGCCGGGUUC	20	9438
  BCL11A-7759	+	CAAGUCGCUGGUGCCGGGUUC	21	9439
  BCL11A-7760	+	CCAAGUCGCUGGUGCCGGGUUC	22	9440
  BCL11A-7761	+	ACCAAGUCGCUGGUGCCGGGUUC	23	9441
  BCL11A-7762	+	CACCAAGUCGCUGGUGCCGGGUUC	24	9442
  BCL11A-7763	+	CGGUGGUGGACUAAACAG	18	9443
  BCL11A-7764	+	UCGGUGGUGGACUAAACAG	19	9444
  BCL11A-6063	+	CUCGGUGGUGGACUAAACAG	20	9445
  BCL11A-7765	+	UCUCGGUGGUGGACUAAACAG	21	9446
  BCL11A-7766	+	GUCUCGGUGGUGGACUAAACAG	22	9447
  BCL11A-7767	+	UGUCUCGGUGGUGGACUAAACAG	23	9448
  BCL11A-7768	+	AUGUCUCGGUGGUGGACUAAACAG	24	9449
  BCL11A-7769	+	GAAAGAGGUUGGAGACAG	18	9450
  BCL11A-7770	+	AGAAAGAGGUUGGAGACAG	19	9451
  BCL11A-6064	+	UAGAAAGAGGUUGGAGACAG	20	9452
  BCL11A-7771	+	CUAGAAAGAGGUUGGAGACAG	21	9453
  BCL11A-7772	+	CCUAGAAAGAGGUUGGAGACAG	22	9454
  BCL11A-7773	+	ACCUAGAAAGAGGUUGGAGACAG	23	9455
  BCL11A-7774	+	AACCUAGAAAGAGGUUGGAGACAG	24	9456
  BCL11A-7775	+	AGGAGGGGCGGAUUGCAG	18	9457
  BCL11A-7776	+	GAGGAGGGGCGGAUUGCAG	19	9458
  BCL11A-6069	+	GGAGGAGGGGCGGAUUGCAG	20	9459
  BCL11A-7777	+	GGGAGGAGGGGCGGAUUGCAG	21	9460
  BCL11A-7778	+	AGGGAGGAGGGGCGGAUUGCAG	22	9461
  BCL11A-7779	+	GAGGGAGGAGGGGCGGAUUGCAG	23	9462
  BCL11A-7780	+	GGAGGGAGGAGGGGCGGAUUGCAG	24	9463
  BCL11A-7781	+	AAGAGGUUGGAGACAGAG	18	9464
  BCL11A-7782	+	AAAGAGGUUGGAGACAGAG	19	9465
  BCL11A-7783	+	GAAAGAGGUUGGAGACAGAG	20	9466
  BCL11A-7784	+	AGAAAGAGGUUGGAGACAGAG	21	9467
  BCL11A-7785	+	UAGAAAGAGGUUGGAGACAGAG	22	9468
  BCL11A-7786	+	CUAGAAAGAGGUUGGAGACAGAG	23	9469
  BCL11A-7787	+	CCUAGAAAGAGGUUGGAGACAGAG	24	9470
  BCL11A-7788	+	GAGGGGCGGAUUGCAGAG	18	9471
  BCL11A-7789	+	GGAGGGGCGGAUUGCAGAG	19	9472
  BCL11A-7790	+	AGGAGGGGCGGAUUGCAGAG	20	9473
  BCL11A-7791	+	GAGGAGGGGCGGAUUGCAGAG	21	9474
  BCL11A-7792	+	GGAGGAGGGGCGGAUUGCAGAG	22	9475
  BCL11A-7793	+	GGGAGGAGGGGCGGAUUGCAGAG	23	9476
  BCL11A-7794	+	AGGGAGGAGGGGCGGAUUGCAGAG	24	9477
  BCL11A-7795	+	AGCUUGAUGCGCUUAGAG	18	9478
  BCL11A-7796	+	GAGCUUGAUGCGCUUAGAG	19	9479
  BCL11A-7797	+	CGAGCUUGAUGCGCUUAGAG	20	9480
  BCL11A-7798	+	UCGAGCUUGAUGCGCUUAGAG	21	9481
  BCL11A-7799	+	CUCGAGCUUGAUGCGCUUAGAG	22	9482
  BCL11A-7800	+	UCUCGAGCUUGAUGCGCUUAGAG	23	9483
  BCL11A-7801	+	UUCUCGAGCUUGAUGCGCUUAGAG	24	9484
  BCL11A-7802	+	GAGAAGGGGCUCAGCGAG	18	9485
  BCL11A-7803	+	AGAGAAGGGGCUCAGCGAG	19	9486
  BCL11A-7804	+	UAGAGAAGGGGCUCAGCGAG	20	9487
  BCL11A-7805	+	UUAGAGAAGGGGCUCAGCGAG	21	9488
  BCL11A-7806	+	CUUAGAGAAGGGGCUCAGCGAG	22	9489
  BCL11A-7807	+	GCUUAGAGAAGGGGCUCAGCGAG	23	9490
  BCL11A-7808	+	CGCUUAGAGAAGGGGCUCAGCGAG	24	9491
  BCL11A-7809	+	GGAUUGCAGAGGAGGGAG	18	9492
  BCL11A-7810	+	CGGAUUGCAGAGGAGGGAG	19	9493
  BCL11A-6075	+	GCGGAUUGCAGAGGAGGGAG	20	9494
  BCL11A-7811	+	GGCGGAUUGCAGAGGAGGGAG	21	9495
  BCL11A-7812	+	GGGCGGAUUGCAGAGGAGGGAG	22	9496
  BCL11A-7813	+	GGGGCGGAUUGCAGAGGAGGGAG	23	9497
  BCL11A-7814	+	AGGGGCGGAUUGCAGAGGAGGGAG	24	9498
  BCL11A-7815	+	CCGGGGGCUGGGAGGGAG	18	9499
  BCL11A-7816	+	ACCGGGGGCUGGGAGGGAG	19	9500
  BCL11A-7817	+	GACCGGGGGCUGGGAGGGAG	20	9501
  BCL11A-7818	+	UGACCGGGGGCUGGGAGGGAG	21	9502
  BCL11A-7819	+	UUGACCGGGGGCUGGGAGGGAG	22	9503
  BCL11A-7820	+	CUUGACCGGGGGCUGGGAGGGAG	23	9504
  BCL11A-7821	+	ACUUGACCGGGGGCUGGGAGGGAG	24	9505
  BCL11A-7822	+	CUGAAGUGCUGCAUGGAG	18	9506
  BCL11A-7823	+	GCUGAAGUGCUGCAUGGAG	19	9507
  BCL11A-7824	+	CGCUGAAGUGCUGCAUGGAG	20	9508
  BCL11A-7825	+	UCGCUGAAGUGCUGCAUGGAG	21	9509
  BCL11A-7826	+	CUCGCUGAAGUGCUGCAUGGAG	22	9510
  BCL11A-7827	+	CCUCGCUGAAGUGCUGCAUGGAG	23	9511
  BCL11A-7828	+	GCCUCGCUGAAGUGCUGCAUGGAG	24	9512
  BCL11A-7829	+	CGUCUGCCCUCUUUUGAG	18	9513
  BCL11A-7830	+	GCGUCUGCCCUCUUUUGAG	19	9514
  BCL11A-7831	+	UGCGUCUGCCCUCUUUUGAG	20	9515
  BCL11A-7832	+	CUGCGUCUGCCCUCUUUUGAG	21	9516
  BCL11A-7833	+	GCUGCGUCUGCCCUCUUUUGAG	22	9517
  BCL11A-7834	+	CGCUGCGUCUGCCCUCUUUUGAG	23	9518
  BCL11A-7835	+	UCGCUGCGUCUGCCCUCUUUUGAG	24	9519
  BCL11A-7836	+	CCGAGGAGUGCUCCGACG	18	9520
  BCL11A-7837	+	UCCGAGGAGUGCUCCGACG	19	9521
  BCL11A-6080	+	CUCCGAGGAGUGCUCCGACG	20	9522
  BCL11A-7838	+	UCUCCGAGGAGUGCUCCGACG	21	9523
  BCL11A-7839	+	UUCUCCGAGGAGUGCUCCGACG	22	9524
  BCL11A-7840	+	GUUCUCCGAGGAGUGCUCCGACG	23	9525
  BCL11A-7841	+	CGUUCUCCGAGGAGUGCUCCGACG	24	9526
  BCL11A-7842	+	ACCAUGCCCUGCAUGACG	18	9527
  BCL11A-7843	+	CACCAUGCCCUGCAUGACG	19	9528
  BCL11A-7844	+	GCACCAUGCCCUGCAUGACG	20	9529
  BCL11A-7845	+	AGCACCAUGCCCUGCAUGACG	21	9530
  BCL11A-7846	+	GAGCACCAUGCCCUGCAUGACG	22	9531
  BCL11A-7847	+	UGAGCACCAUGCCCUGCAUGACG	23	9532
  BCL11A-7848	+	CUGAGCACCAUGCCCUGCAUGACG	24	9533
  BCL11A-7849	+	CCGAGGCCGACUCGCCCG	18	9534
  BCL11A-7850	+	CCCGAGGCCGACUCGCCCG	19	9535
  BCL11A-6088	+	CCCCGAGGCCGACUCGCCCG	20	9536
  BCL11A-7851	+	CCCCCGAGGCCGACUCGCCCG	21	9537
  BCL11A-7852	+	CCCCCCGAGGCCGACUCGCCCG	22	9538
  BCL11A-7853	+	GCCCCCCGAGGCCGACUCGCCCG	23	9539
  BCL11A-7854	+	GGCCCCCCGAGGCCGACUCGCCCG	24	9540
  BCL11A-7855	+	CUGGAGGCCGCGUAGCCG	18	9541
  BCL11A-7856	+	CCUGGAGGCCGCGUAGCCG	19	9542
  BCL11A-7857	+	GCCUGGAGGCCGCGUAGCCG	20	9543
  BCL11A-7858	+	UGCCUGGAGGCCGCGUAGCCG	21	9544
  BCL11A-7859	+	CUGCCUGGAGGCCGCGUAGCCG	22	9545
  BCL11A-7860	+	GCUGCCUGGAGGCCGCGUAGCCG	23	9546
  BCL11A-7861	+	AGCUGCCUGGAGGCCGCGUAGCCG	24	9547
  BCL11A-7862	+	AAUUUGAACGUCUUGCCG	18	9548
  BCL11A-7863	+	AAAUUUGAACGUCUUGCCG	19	9549
  BCL11A-7864	+	GAAAUUUGAACGUCUUGCCG	20	9550
  BCL11A-7865	+	UGAAAUUUGAACGUCUUGCCG	21	9551
  BCL11A-7866	+	CUGAAAUUUGAACGUCUUGCCG	22	9552
  BCL11A-7867	+	UCUGAAAUUUGAACGUCUUGCCG	23	9553
  BCL11A-7868	+	CUCUGAAAUUUGAACGUCUUGCCG	24	9554
  BCL11A-7869	+	UCUCCGAGGAGUGCUCCG	18	9555
  BCL11A-7870	+	UUCUCCGAGGAGUGCUCCG	19	9556
  BCL11A-7871	+	GUUCUCCGAGGAGUGCUCCG	20	9557
  BCL11A-7872	+	CGUUCUCCGAGGAGUGCUCCG	21	9558
  BCL11A-7873	+	CCGUUCUCCGAGGAGUGCUCCG	22	9559
  BCL11A-7874	+	CCCGUUCUCCGAGGAGUGCUCCG	23	9560
  BCL11A-7875	+	UCCCGUUCUCCGAGGAGUGCUCCG	24	9561
  BCL11A-7876	+	CGCUGGUGCCGGGUUCCG	18	9562
  BCL11A-7877	+	UCGCUGGUGCCGGGUUCCG	19	9563
  BCL11A-6096	+	GUCGCUGGUGCCGGGUUCCG	20	9564
  BCL11A-7878	+	AGUCGCUGGUGCCGGGUUCCG	21	9565
  BCL11A-7879	+	AAGUCGCUGGUGCCGGGUUCCG	22	9566
  BCL11A-7880	+	CAAGUCGCUGGUGCCGGGUUCCG	23	9567
  BCL11A-7881	+	CCAAGUCGCUGGUGCCGGGUUCCG	24	9568
  BCL11A-7882	+	GCCGGCCUGGGGACAGCG	18	9569
  BCL11A-7883	+	GGCCGGCCUGGGGACAGCG	19	9570
  BCL11A-7884	+	GGGCCGGCCUGGGGACAGCG	20	9571
  BCL11A-7885	+	UGGGCCGGCCUGGGGACAGCG	21	9572
  BCL11A-7886	+	CUGGGCCGGCCUGGGGACAGCG	22	9573
  BCL11A-7887	+	GCUGGGCCGGCCUGGGGACAGCG	23	9574
  BCL11A-7888	+	GGCUGGGCCGGCCUGGGGACAGCG	24	9575
  BCL11A-7889	+	GGUUCCGGGGAGCUGGCG	18	9576
  BCL11A-7890	+	GGGUUCCGGGGAGCUGGCG	19	9577
  BCL11A-7891	+	CGGGUUCCGGGGAGCUGGCG	20	9578
  BCL11A-7892	+	CCGGGUUCCGGGGAGCUGGCG	21	9579
  BCL11A-7893	+	GCCGGGUUCCGGGGAGCUGGCG	22	9580
  BCL11A-7894	+	UGCCGGGUUCCGGGGAGCUGGCG	23	9581
  BCL11A-7895	+	GUGCCGGGUUCCGGGGAGCUGGCG	24	9582
  BCL11A-7896	+	CCCCAGGCGCUCUAUGCG	18	9583
  BCL11A-7897	+	CCCCCAGGCGCUCUAUGCG	19	9584
  BCL11A-7898	+	GCCCCCAGGCGCUCUAUGCG	20	9585
  BCL11A-7899	+	CGCCCCCAGGCGCUCUAUGCG	21	9586
  BCL11A-7900	+	CCGCCCCCAGGCGCUCUAUGCG	22	9587
  BCL11A-7901	+	UCCGCCCCCAGGCGCUCUAUGCG	23	9588
  BCL11A-7902	+	UUCCGCCCCCAGGCGCUCUAUGCG	24	9589
  BCL11A-7903	+	ACCUGGUGGAAGGCCUCG	18	9590
  BCL11A-7904	+	GACCUGGUGGAAGGCCUCG	19	9591
  BCL11A-7905	+	GGACCUGGUGGAAGGCCUCG	20	9592
  BCL11A-7906	+	AGGACCUGGUGGAAGGCCUCG	21	9593
  BCL11A-7907	+	CAGGACCUGGUGGAAGGCCUCG	22	9594
  BCL11A-7908	+	CCAGGACCUGGUGGAAGGCCUCG	23	9595
  BCL11A-7909	+	CCCAGGACCUGGUGGAAGGCCUCG	24	9596
  BCL11A-7910	+	GCGGUGGAGAGACCGUCG	18	9597
  BCL11A-7911	+	GGCGGUGGAGAGACCGUCG	19	9598
  BCL11A-7912	+	UGGCGGUGGAGAGACCGUCG	20	9599
  BCL11A-7913	+	CUGGCGGUGGAGAGACCGUCG	21	9600
  BCL11A-7914	+	GCUGGCGGUGGAGAGACCGUCG	22	9601
  BCL11A-7915	+	AGCUGGCGGUGGAGAGACCGUCG	23	9602
  BCL11A-7916	+	GAGCUGGCGGUGGAGAGACCGUCG	24	9603
  BCL11A-7917	+	GAGUCUCCGAAGCUAAGG	18	9604
  BCL11A-7918	+	GGAGUCUCCGAAGCUAAGG	19	9605
  BCL11A-7919	+	UGGAGUCUCCGAAGCUAAGG	20	9606
  BCL11A-7920	+	CUGGAGUCUCCGAAGCUAAGG	21	9607
  BCL11A-7921	+	UCUGGAGUCUCCGAAGCUAAGG	22	9608
  BCL11A-7922	+	GUCUGGAGUCUCCGAAGCUAAGG	23	9609
  BCL11A-7923	+	UGUCUGGAGUCUCCGAAGCUAAGG	24	9610
  BCL11A-7924	+	GGUGGUGGACUAAACAGG	18	9611
  BCL11A-7925	+	CGGUGGUGGACUAAACAGG	19	9612
  BCL11A-6111	+	UCGGUGGUGGACUAAACAGG	20	9613
  BCL11A-7926	+	CUCGGUGGUGGACUAAACAGG	21	9614
  BCL11A-7927	+	UCUCGGUGGUGGACUAAACAGG	22	9615
  BCL11A-7928	+	GUCUCGGUGGUGGACUAAACAGG	23	9616
  BCL11A-7929	+	UGUCUCGGUGGUGGACUAAACAGG	24	9617
  BCL11A-7930	+	AGGGGGGGCGUCGCCAGG	18	9618
  BCL11A-7931	+	GAGGGGGGGCGUCGCCAGG	19	9619
  BCL11A-7932	+	GGAGGGGGGGCGUCGCCAGG	20	9620
  BCL11A-7933	+	GGGAGGGGGGGCGUCGCCAGG	21	9621
  BCL11A-7934	+	AGGGAGGGGGGGCGUCGCCAGG	22	9622
  BCL11A-7935	+	GAGGGAGGGGGGGCGUCGCCAGG	23	9623
  BCL11A-7936	+	GGAGGGAGGGGGGGCGUCGCCAGG	24	9624
  BCL11A-7937	+	AAGCGCCCUUCUGCCAGG	18	9625
  BCL11A-7938	+	AAAGCGCCCUUCUGCCAGG	19	9626
  BCL11A-7939	+	GAAAGCGCCCUUCUGCCAGG	20	9627
  BCL11A-7940	+	GGAAAGCGCCCUUCUGCCAGG	21	9628
  BCL11A-7941	+	UGGAAAGCGCCCUUCUGCCAGG	22	9629
  BCL11A-7942	+	GUGGAAAGCGCCCUUCUGCCAGG	23	9630
  BCL11A-7943	+	GGUGGAAAGCGCCCUUCUGCCAGG	24	9631
  BCL11A-7944	+	AUCGCGGCCGGGGGCAGG	18	9632
  BCL11A-7945	+	CAUCGCGGCCGGGGGCAGG	19	9633
  BCL11A-7946	+	GCAUCGCGGCCGGGGGCAGG	20	9634
  BCL11A-7947	+	GGCAUCGCGGCCGGGGGCAGG	21	9635
  BCL11A-7948	+	GGGCAUCGCGGCCGGGGGCAGG	22	9636
  BCL11A-7949	+	UGGGCAUCGCGGCCGGGGGCAGG	23	9637
  BCL11A-7950	+	UUGGGCAUCGCGGCCGGGGGCAGG	24	9638
  BCL11A-7951	+	CCGUUCUCCGGGAUCAGG	18	9639
  BCL11A-7952	+	CCCGUUCUCCGGGAUCAGG	19	9640
  BCL11A-7953	+	CCCCGUUCUCCGGGAUCAGG	20	9641
  BCL11A-7954	+	UCCCCGUUCUCCGGGAUCAGG	21	9642
  BCL11A-7955	+	GUCCCCGUUCUCCGGGAUCAGG	22	9643
  BCL11A-7956	+	CGUCCCCGUUCUCCGGGAUCAGG	23	9644
  BCL11A-7957	+	UCGUCCCCGUUCUCCGGGAUCAGG	24	9645
  BCL11A-7958	+	GAAGAACCUAGAAAGAGG	18	9646
  BCL11A-7959	+	UGAAGAACCUAGAAAGAGG	19	9647
  BCL11A-7960	+	GUGAAGAACCUAGAAAGAGG	20	9648
  BCL11A-7961	+	UGUGAAGAACCUAGAAAGAGG	21	9649
  BCL11A-7962	+	GUGUGAAGAACCUAGAAAGAGG	22	9650
  BCL11A-7963	+	UGUGUGAAGAACCUAGAAAGAGG	23	9651
  BCL11A-7964	+	GUGUGUGAAGAACCUAGAAAGAGG	24	9652
  BCL11A-7965	+	AGAGGUUGGAGACAGAGG	18	9653
  BCL11A-7966	+	AAGAGGUUGGAGACAGAGG	19	9654
  BCL11A-6113	+	AAAGAGGUUGGAGACAGAGG	20	9655
  BCL11A-7967	+	GAAAGAGGUUGGAGACAGAGG	21	9656
  BCL11A-7968	+	AGAAAGAGGUUGGAGACAGAGG	22	9657
  BCL11A-7969	+	UAGAAAGAGGUUGGAGACAGAGG	23	9658
  BCL11A-7970	+	CUAGAAAGAGGUUGGAGACAGAGG	24	9659
  BCL11A-7971	+	AGGGGCGGAUUGCAGAGG	18	9660
  BCL11A-7972	+	GAGGGGCGGAUUGCAGAGG	19	9661
  BCL11A-6114	+	GGAGGGGCGGAUUGCAGAGG	20	9662
  BCL11A-7973	+	AGGAGGGGCGGAUUGCAGAGG	21	9663
  BCL11A-7974	+	GAGGAGGGGCGGAUUGCAGAGG	22	9664
  BCL11A-7975	+	GGAGGAGGGGCGGAUUGCAGAGG	23	9665
  BCL11A-7976	+	GGGAGGAGGGGCGGAUUGCAGAGG	24	9666
  BCL11A-7977	+	GGCGGAUUGCAGAGGAGG	18	9667
  BCL11A-7978	+	GGGCGGAUUGCAGAGGAGG	19	9668
  BCL11A-7979	+	GGGGCGGAUUGCAGAGGAGG	20	9669
  BCL11A-7980	+	AGGGGCGGAUUGCAGAGGAGG	21	9670
  BCL11A-7981	+	GAGGGGCGGAUUGCAGAGGAGG	22	9671
  BCL11A-7982	+	GGAGGGGCGGAUUGCAGAGGAGG	23	9672
  BCL11A-7983	+	AGGAGGGGCGGAUUGCAGAGGAGG	24	9673
  BCL11A-7984	+	GAUUGCAGAGGAGGGAGG	18	9674
  BCL11A-7985	+	GGAUUGCAGAGGAGGGAGG	19	9675
  BCL11A-6118	+	CGGAUUGCAGAGGAGGGAGG	20	9676
  BCL11A-7986	+	GCGGAUUGCAGAGGAGGGAGG	21	9677
  BCL11A-7987	+	GGCGGAUUGCAGAGGAGGGAGG	22	9678
  BCL11A-7988	+	GGGCGGAUUGCAGAGGAGGGAGG	23	9679
  BCL11A-7989	+	GGGGCGGAUUGCAGAGGAGGGAGG	24	9680
  BCL11A-7990	+	CGGGGGCUGGGAGGGAGG	18	9681
  BCL11A-7991	+	CCGGGGGCUGGGAGGGAGG	19	9682
  BCL11A-6119	+	ACCGGGGGCUGGGAGGGAGG	20	9683
  BCL11A-7992	+	GACCGGGGGCUGGGAGGGAGG	21	9684
  BCL11A-7993	+	UGACCGGGGGCUGGGAGGGAGG	22	9685
  BCL11A-7994	+	UUGACCGGGGGCUGGGAGGGAGG	23	9686
  BCL11A-7995	+	CUUGACCGGGGGCUGGGAGGGAGG	24	9687
  BCL11A-7996	+	UGACCGGGGGCUGGGAGG	18	9688
  BCL11A-7997	+	UUGACCGGGGGCUGGGAGG	19	9689
  BCL11A-7998	+	CUUGACCGGGGGCUGGGAGG	20	9690
  BCL11A-7999	+	ACUUGACCGGGGGCUGGGAGG	21	9691
  BCL11A-8000	+	GACUUGACCGGGGGCUGGGAGG	22	9692
  BCL11A-8001	+	GGACUUGACCGGGGGCUGGGAGG	23	9693
  BCL11A-8002	+	UGGACUUGACCGGGGGCUGGGAGG	24	9694
  BCL11A-8003	+	CCGUGUUGGGCAUCGCGG	18	9695
  BCL11A-8004	+	UCCGUGUUGGGCAUCGCGG	19	9696
  BCL11A-8005	+	CUCCGUGUUGGGCAUCGCGG	20	9697
  BCL11A-8006	+	UCUCCGUGUUGGGCAUCGCGG	21	9698
  BCL11A-8007	+	UUCUCCGUGUUGGGCAUCGCGG	22	9699
  BCL11A-8008	+	GUUCUCCGUGUUGGGCAUCGCGG	23	9700
  BCL11A-8009	+	CGUUCUCCGUGUUGGGCAUCGCGG	24	9701
  BCL11A-8010	+	GUUCCGGGGAGCUGGCGG	18	9702
  BCL11A-8011	+	GGUUCCGGGGAGCUGGCGG	19	9703
  BCL11A-6125	+	GGGUUCCGGGGAGCUGGCGG	20	9704
  BCL11A-8012	+	CGGGUUCCGGGGAGCUGGCGG	21	9705
  BCL11A-8013	+	CCGGGUUCCGGGGAGCUGGCGG	22	9706
  BCL11A-8014	+	GCCGGGUUCCGGGGAGCUGGCGG	23	9707
  BCL11A-8015	+	UGCCGGGUUCCGGGGAGCUGGCGG	24	9708
  BCL11A-8016	+	CCCAGGCGCUCUAUGCGG	18	9709
  BCL11A-8017	+	CCCCAGGCGCUCUAUGCGG	19	9710
  BCL11A-6126	+	CCCCCAGGCGCUCUAUGCGG	20	9711
  BCL11A-8018	+	GCCCCCAGGCGCUCUAUGCGG	21	9712
  BCL11A-8019	+	CGCCCCCAGGCGCUCUAUGCGG	22	9713
  BCL11A-8020	+	CCGCCCCCAGGCGCUCUAUGCGG	23	9714
  BCL11A-8021	+	UCCGCCCCCAGGCGCUCUAUGCGG	24	9715
  BCL11A-8022	+	GUGGUGGACUAAACAGGG	18	9716
  BCL11A-8023	+	GGUGGUGGACUAAACAGGG	19	9717
  BCL11A-6131	+	CGGUGGUGGACUAAACAGGG	20	9718
  BCL11A-8024	+	UCGGUGGUGGACUAAACAGGG	21	9719
  BCL11A-8025	+	CUCGGUGGUGGACUAAACAGGG	22	9720
  BCL11A-8026	+	UCUCGGUGGUGGACUAAACAGGG	23	9721
  BCL11A-8027	+	GUCUCGGUGGUGGACUAAACAGGG	24	9722
  BCL11A-8028	+	GCGGAUUGCAGAGGAGGG	18	9723
  BCL11A-8029	+	GGCGGAUUGCAGAGGAGGG	19	9724
  BCL11A-6133	+	GGGCGGAUUGCAGAGGAGGG	20	9725
  BCL11A-8030	+	GGGGCGGAUUGCAGAGGAGGG	21	9726
  BCL11A-8031	+	AGGGGCGGAUUGCAGAGGAGGG	22	9727
  BCL11A-8032	+	GAGGGGCGGAUUGCAGAGGAGGG	23	9728
  BCL11A-8033	+	GGAGGGGCGGAUUGCAGAGGAGGG	24	9729
  BCL11A-8034	+	GACCGGGGGCUGGGAGGG	18	9730
  BCL11A-8035	+	UGACCGGGGGCUGGGAGGG	19	9731
  BCL11A-6135	+	UUGACCGGGGGCUGGGAGGG	20	9732
  BCL11A-8036	+	CUUGACCGGGGGCUGGGAGGG	21	9733
  BCL11A-8037	+	ACUUGACCGGGGGCUGGGAGGG	22	9734
  BCL11A-8038	+	GACUUGACCGGGGGCUGGGAGGG	23	9735
  BCL11A-8039	+	GGACUUGACCGGGGGCUGGGAGGG	24	9736
  BCL11A-8040	+	AGUAACCUUUGCAUAGGG	18	9737
  BCL11A-8041	+	CAGUAACCUUUGCAUAGGG	19	9738
  BCL11A-8042	+	GCAGUAACCUUUGCAUAGGG	20	9739
  BCL11A-8043	+	UGCAGUAACCUUUGCAUAGGG	21	9740
  BCL11A-8044	+	UUGCAGUAACCUUUGCAUAGGG	22	9741
  BCL11A-8045	+	GUUGCAGUAACCUUUGCAUAGGG	23	9742
  BCL11A-8046	+	GGUUGCAGUAACCUUUGCAUAGGG	24	9743
  BCL11A-8047	+	GCCCUGCAUGACGUCGGG	18	9744
  BCL11A-8048	+	UGCCCUGCAUGACGUCGGG	19	9745
  BCL11A-8049	+	AUGCCCUGCAUGACGUCGGG	20	9746
  BCL11A-8050	+	CAUGCCCUGCAUGACGUCGGG	21	9747
  BCL11A-8051	+	CCAUGCCCUGCAUGACGUCGGG	22	9748
  BCL11A-8052	+	ACCAUGCCCUGCAUGACGUCGGG	23	9749
  BCL11A-8053	+	CACCAUGCCCUGCAUGACGUCGGG	24	9750
  BCL11A-8054	+	CUUGGACUUGACCGGGGG	18	9751
  BCL11A-8055	+	ACUUGGACUUGACCGGGGG	19	9752
  BCL11A-8056	+	GACUUGGACUUGACCGGGGG	20	9753
  BCL11A-8057	+	UGACUUGGACUUGACCGGGGG	21	9754
  BCL11A-8058	+	AUGACUUGGACUUGACCGGGGG	22	9755
  BCL11A-8059	+	CAUGACUUGGACUUGACCGGGGG	23	9756
  BCL11A-8060	+	GCAUGACUUGGACUUGACCGGGGG	24	9757
  BCL11A-8061	+	ACUUGACCGGGGGCUGGG	18	9758
  BCL11A-8062	+	GACUUGACCGGGGGCUGGG	19	9759
  BCL11A-6146	+	GGACUUGACCGGGGGCUGGG	20	9760
  BCL11A-8063	+	UGGACUUGACCGGGGGCUGGG	21	9761
  BCL11A-8064	+	UUGGACUUGACCGGGGGCUGGG	22	9762
  BCL11A-8065	+	CUUGGACUUGACCGGGGGCUGGG	23	9763
  BCL11A-8066	+	ACUUGGACUUGACCGGGGGCUGGG	24	9764
  BCL11A-8067	+	CAUGGAGAGGUGGCUGGG	18	9765
  BCL11A-8068	+	CCAUGGAGAGGUGGCUGGG	19	9766
  BCL11A-8069	+	CCCAUGGAGAGGUGGCUGGG	20	9767
  BCL11A-8070	+	UCCCAUGGAGAGGUGGCUGGG	21	9768
  BCL11A-8071	+	AUCCCAUGGAGAGGUGGCUGGG	22	9769
  BCL11A-8072	+	AAUCCCAUGGAGAGGUGGCUGGG	23	9770
  BCL11A-8073	+	GAAUCCCAUGGAGAGGUGGCUGGG	24	9771
  BCL11A-8074	+	AAACAGGGGGGGAGUGGG	18	9772
  BCL11A-8075	+	UAAACAGGGGGGGAGUGGG	19	9773
  BCL11A-6147	+	CUAAACAGGGGGGGAGUGGG	20	9774
  BCL11A-8076	+	ACUAAACAGGGGGGGAGUGGG	21	9775
  BCL11A-8077	+	GACUAAACAGGGGGGGAGUGGG	22	9776
  BCL11A-8078	+	GGACUAAACAGGGGGGGAGUGGG	23	9777
  BCL11A-8079	+	UGGACUAAACAGGGGGGGAGUGGG	24	9778
  BCL11A-8080	+	UCCUAGAGAAAUCCAUGG	18	9779
  BCL11A-8081	+	CUCCUAGAGAAAUCCAUGG	19	9780
  BCL11A-6149	+	UCUCCUAGAGAAAUCCAUGG	20	9781
  BCL11A-8082	+	GUCUCCUAGAGAAAUCCAUGG	21	9782
  BCL11A-8083	+	AGUCUCCUAGAGAAAUCCAUGG	22	9783
  BCL11A-8084	+	AAGUCUCCUAGAGAAAUCCAUGG	23	9784
  BCL11A-8085	+	UAAGUCUCCUAGAGAAAUCCAUGG	24	9785
  BCL11A-8086	+	UUCUCGCCCAGGACCUGG	18	9786
  BCL11A-8087	+	CUUCUCGCCCAGGACCUGG	19	9787
  BCL11A-6152	+	GCUUCUCGCCCAGGACCUGG	20	9788
  BCL11A-8088	+	UGCUUCUCGCCCAGGACCUGG	21	9789
  BCL11A-8089	+	AUGCUUCUCGCCCAGGACCUGG	22	9790
  BCL11A-8090	+	UAUGCUUCUCGCCCAGGACCUGG	23	9791
  BCL11A-8091	+	UUAUGCUUCUCGCCCAGGACCUGG	24	9792
  BCL11A-8092	+	GGGCGGCUUGCUACCUGG	18	9793
  BCL11A-8093	+	AGGGCGGCUUGCUACCUGG	19	9794
  BCL11A-8094	+	AAGGGCGGCUUGCUACCUGG	20	9795
  BCL11A-8095	+	GAAGGGCGGCUUGCUACCUGG	21	9796
  BCL11A-8096	+	GGAAGGGCGGCUUGCUACCUGG	22	9797
  BCL11A-8097	+	AGGAAGGGCGGCUUGCUACCUGG	23	9798
  BCL11A-8098	+	CAGGAAGGGCGGCUUGCUACCUGG	24	9799
  BCL11A-8099	+	GACUUGACCGGGGGCUGG	18	9800
  BCL11A-8100	+	GGACUUGACCGGGGGCUGG	19	9801
  BCL11A-8101	+	UGGACUUGACCGGGGGCUGG	20	9802
  BCL11A-8102	+	UUGGACUUGACCGGGGGCUGG	21	9803
  BCL11A-8103	+	CUUGGACUUGACCGGGGGCUGG	22	9804
  BCL11A-8104	+	ACUUGGACUUGACCGGGGGCUGG	23	9805
  BCL11A-8105	+	GACUUGGACUUGACCGGGGGCUGG	24	9806
  BCL11A-8106	+	UAAACAGGGGGGGAGUGG	18	9807
  BCL11A-8107	+	CUAAACAGGGGGGGAGUGG	19	9808
  BCL11A-8108	+	ACUAAACAGGGGGGGAGUGG	20	9809
  BCL11A-8109	+	GACUAAACAGGGGGGGAGUGG	21	9810
  BCL11A-8110	+	GGACUAAACAGGGGGGGAGUGG	22	9811
  BCL11A-8111	+	UGGACUAAACAGGGGGGGAGUGG	23	9812
  BCL11A-8112	+	GUGGACUAAACAGGGGGGGAGUGG	24	9813
  BCL11A-8113	+	AAUCCCAUGGAGAGGUGG	18	9814
  BCL11A-8114	+	GAAUCCCAUGGAGAGGUGG	19	9815
  BCL11A-8115	+	UGAAUCCCAUGGAGAGGUGG	20	9816
  BCL11A-8116	+	AUGAAUCCCAUGGAGAGGUGG	21	9817
  BCL11A-8117	+	UAUGAAUCCCAUGGAGAGGUGG	22	9818
  BCL11A-8118	+	AUAUGAAUCCCAUGGAGAGGUGG	23	9819
  BCL11A-8119	+	AAUAUGAAUCCCAUGGAGAGGUGG	24	9820
  BCL11A-8120	+	UGCAAUAUGAAUCCCAUG	18	9821
  BCL11A-8121	+	CUGCAAUAUGAAUCCCAUG	19	9822
  BCL11A-8122	+	UCUGCAAUAUGAAUCCCAUG	20	9823
  BCL11A-8123	+	GUCUGCAAUAUGAAUCCCAUG	21	9824
  BCL11A-8124	+	UGUCUGCAAUAUGAAUCCCAUG	22	9825
  BCL11A-8125	+	UUGUCUGCAAUAUGAAUCCCAUG	23	9826
  BCL11A-8126	+	AUUGUCUGCAAUAUGAAUCCCAUG	24	9827
  BCL11A-8127	+	CUCCUAGAGAAAUCCAUG	18	9828
  BCL11A-8128	+	UCUCCUAGAGAAAUCCAUG	19	9829
  BCL11A-8129	+	GUCUCCUAGAGAAAUCCAUG	20	9830
  BCL11A-8130	+	AGUCUCCUAGAGAAAUCCAUG	21	9831
  BCL11A-8131	+	AAGUCUCCUAGAGAAAUCCAUG	22	9832
  BCL11A-8132	+	UAAGUCUCCUAGAGAAAUCCAUG	23	9833
  BCL11A-8133	+	CUAAGUCUCCUAGAGAAAUCCAUG	24	9834
  BCL11A-8134	+	UCGGACUUGACCGUCAUG	18	9835
  BCL11A-8135	+	GUCGGACUUGACCGUCAUG	19	9836
  BCL11A-6164	+	CGUCGGACUUGACCGUCAUG	20	9837
  BCL11A-8136	+	UCGUCGGACUUGACCGUCAUG	21	9838
  BCL11A-8137	+	GUCGUCGGACUUGACCGUCAUG	22	9839
  BCL11A-8138	+	CGUCGUCGGACUUGACCGUCAUG	23	9840
  BCL11A-8139	+	CCGUCGUCGGACUUGACCGUCAUG	24	9841
  BCL11A-8140	+	CUUCUCGCCCAGGACCUG	18	9842
  BCL11A-8141	+	GCUUCUCGCCCAGGACCUG	19	9843
  BCL11A-8142	+	UGCUUCUCGCCCAGGACCUG	20	9844
  BCL11A-8143	+	AUGCUUCUCGCCCAGGACCUG	21	9845
  BCL11A-8144	+	UAUGCUUCUCGCCCAGGACCUG	22	9846
  BCL11A-8145	+	UUAUGCUUCUCGCCCAGGACCUG	23	9847
  BCL11A-8146	+	CUUAUGCUUCUCGCCCAGGACCUG	24	9848
  BCL11A-8147	+	AUUCUGCACCUAGUCCUG	18	9849
  BCL11A-8148	+	CAUUCUGCACCUAGUCCUG	19	9850
  BCL11A-8149	+	ACAUUCUGCACCUAGUCCUG	20	9851
  BCL11A-8150	+	GACAUUCUGCACCUAGUCCUG	21	9852
  BCL11A-8151	+	GGACAUUCUGCACCUAGUCCUG	22	9853
  BCL11A-8152	+	AGGACAUUCUGCACCUAGUCCUG	23	9854
  BCL11A-8153	+	AAGGACAUUCUGCACCUAGUCCUG	24	9855
  BCL11A-6537	+	GUUGUACAUGUGUAGCUG	18	9856
  BCL11A-6538	+	AGUUGUACAUGUGUAGCUG	19	9857
  BCL11A-6539	+	AAGUUGUACAUGUGUAGCUG	20	9858
  BCL11A-6540	+	CAAGUUGUACAUGUGUAGCUG	21	9859
  BCL11A-6541	+	GCAAGUUGUACAUGUGUAGCUG	22	9860
  BCL11A-6542	+	UGCAAGUUGUACAUGUGUAGCUG	23	9861
  BCL11A-6543	+	UUGCAAGUUGUACAUGUGUAGCUG	24	9862
  BCL11A-8154	+	GAGUACACGUUCUCCGUG	18	9863
  BCL11A-8155	+	CGAGUACACGUUCUCCGUG	19	9864
  BCL11A-8156	+	GCGAGUACACGUUCUCCGUG	20	9865
  BCL11A-8157	+	UGCGAGUACACGUUCUCCGUG	21	9866
  BCL11A-8158	+	CUGCGAGUACACGUUCUCCGUG	22	9867
  BCL11A-8159	+	ACUGCGAGUACACGUUCUCCGUG	23	9868
  BCL11A-8160	+	CACUGCGAGUACACGUUCUCCGUG	24	9869
  BCL11A-8161	+	CCAGCUCCCCGGGCGGUG	18	9870
  BCL11A-8162	+	UCCAGCUCCCCGGGCGGUG	19	9871
  BCL11A-6177	+	GUCCAGCUCCCCGGGCGGUG	20	9872
  BCL11A-8163	+	CGUCCAGCUCCCCGGGCGGUG	21	9873
  BCL11A-8164	+	CCGUCCAGCUCCCCGGGCGGUG	22	9874
  BCL11A-8165	+	UCCGUCCAGCUCCCCGGGCGGUG	23	9875
  BCL11A-8166	+	CUCCGUCCAGCUCCCCGGGCGGUG	24	9876
  BCL11A-8167	+	UCCGGGGAGCUGGCGGUG	18	9877
  BCL11A-8168	+	UUCCGGGGAGCUGGCGGUG	19	9878
  BCL11A-8169	+	GUUCCGGGGAGCUGGCGGUG	20	9879
  BCL11A-8170	+	GGUUCCGGGGAGCUGGCGGUG	21	9880
  BCL11A-8171	+	GGGUUCCGGGGAGCUGGCGGUG	22	9881
  BCL11A-8172	+	CGGGUUCCGGGGAGCUGGCGGUG	23	9882
  BCL11A-8173	+	CCGGGUUCCGGGGAGCUGGCGGUG	24	9883
  BCL11A-8174	+	CCAAGUGAUGUCUCGGUG	18	9884
  BCL11A-8175	+	UCCAAGUGAUGUCUCGGUG	19	9885
  BCL11A-8176	+	GUCCAAGUGAUGUCUCGGUG	20	9886
  BCL11A-8177	+	GGUCCAAGUGAUGUCUCGGUG	21	9887
  BCL11A-8178	+	GGGUCCAAGUGAUGUCUCGGUG	22	9888
  BCL11A-8179	+	GGGGUCCAAGUGAUGUCUCGGUG	23	9889
  BCL11A-8180	+	GGGGGUCCAAGUGAUGUCUCGGUG	24	9890
  BCL11A-8181	+	AGCUCCCCGGGCGGUGUG	18	9891
  BCL11A-8182	+	CAGCUCCCCGGGCGGUGUG	19	9892
  BCL11A-8183	+	CCAGCUCCCCGGGCGGUGUG	20	9893
  BCL11A-8184	+	UCCAGCUCCCCGGGCGGUGUG	21	9894
  BCL11A-8185	+	GUCCAGCUCCCCGGGCGGUGUG	22	9895
  BCL11A-8186	+	CGUCCAGCUCCCCGGGCGGUGUG	23	9896
  BCL11A-8187	+	CCGUCCAGCUCCCCGGGCGGUGUG	24	9897
  BCL11A-8188	+	GCCGAAUGGGGGUGUGUG	18	9898
  BCL11A-8189	+	CGCCGAAUGGGGGUGUGUG	19	9899
  BCL11A-8190	+	ACGCCGAAUGGGGGUGUGUG	20	9900
  BCL11A-8191	+	UACGCCGAAUGGGGGUGUGUG	21	9901
  BCL11A-8192	+	CUACGCCGAAUGGGGGUGUGUG	22	9902
  BCL11A-8193	+	ACUACGCCGAAUGGGGGUGUGUG	23	9903
  BCL11A-8194	+	UACUACGCCGAAUGGGGGUGUGUG	24	9904
  BCL11A-8195	+	GGGAGGAGGGGCGGAUUG	18	9905
  BCL11A-8196	+	AGGGAGGAGGGGCGGAUUG	19	9906
  BCL11A-8197	+	GAGGGAGGAGGGGCGGAUUG	20	9907
  BCL11A-8198	+	GGAGGGAGGAGGGGCGGAUUG	21	9908
  BCL11A-8199	+	GGGAGGGAGGAGGGGCGGAUUG	22	9909
  BCL11A-8200	+	UGGGAGGGAGGAGGGGCGGAUUG	23	9910
  BCL11A-8201	+	CUGGGAGGGAGGAGGGGCGGAUUG	24	9911
  BCL11A-8202	+	UCGCACAGGUUGCACUUG	18	9912
  BCL11A-8203	+	GUCGCACAGGUUGCACUUG	19	9913
  BCL11A-8204	+	GGUCGCACAGGUUGCACUUG	20	9914
  BCL11A-8205	+	UGGUCGCACAGGUUGCACUUG	21	9915
  BCL11A-8206	+	GUGGUCGCACAGGUUGCACUUG	22	9916
  BCL11A-8207	+	CGUGGUCGCACAGGUUGCACUUG	23	9917
  BCL11A-8208	+	GCGUGGUCGCACAGGUUGCACUUG	24	9918
  BCL11A-8209	+	ACCAGGUUGCUCUGAAAU	18	9919
  BCL11A-8210	+	CACCAGGUUGCUCUGAAAU	19	9920
  BCL11A-8211	+	CCACCAGGUUGCUCUGAAAU	20	9921
  BCL11A-8212	+	ACCACCAGGUUGCUCUGAAAU	21	9922
  BCL11A-8213	+	CACCACCAGGUUGCUCUGAAAU	22	9923
  BCL11A-8214	+	GCACCACCAGGUUGCUCUGAAAU	23	9924
  BCL11A-8215	+	UGCACCACCAGGUUGCUCUGAAAU	24	9925
  BCL11A-8216	+	CGGGCCCGGACCACUAAU	18	9926
  BCL11A-8217	+	CCGGGCCCGGACCACUAAU	19	9927
  BCL11A-8218	+	CCCGGGCCCGGACCACUAAU	20	9928
  BCL11A-8219	+	GCCCGGGCCCGGACCACUAAU	21	9929
  BCL11A-8220	+	UGCCCGGGCCCGGACCACUAAU	22	9930
  BCL11A-8221	+	CUGCCCGGGCCCGGACCACUAAU	23	9931
  BCL11A-8222	+	CCUGCCCGGGCCCGGACCACUAAU	24	9932
  BCL11A-8223	+	GGGCUCUCGAGCUUCCAU	18	9933
  BCL11A-8224	+	AGGGCUCUCGAGCUUCCAU	19	9934
  BCL11A-8225	+	AAGGGCUCUCGAGCUUCCAU	20	9935
  BCL11A-8226	+	UAAGGGCUCUCGAGCUUCCAU	21	9936
  BCL11A-8227	+	UUAAGGGCUCUCGAGCUUCCAU	22	9937
  BCL11A-8228	+	CUUAAGGGCUCUCGAGCUUCCAU	23	9938
  BCL11A-8229	+	ACUUAAGGGCUCUCGAGCUUCCAU	24	9939
  BCL11A-8230	+	GUCGGACUUGACCGUCAU	18	9940
  BCL11A-8231	+	CGUCGGACUUGACCGUCAU	19	9941
  BCL11A-6186	+	UCGUCGGACUUGACCGUCAU	20	9942
  BCL11A-8232	+	GUCGUCGGACUUGACCGUCAU	21	9943
  BCL11A-8233	+	CGUCGUCGGACUUGACCGUCAU	22	9944
  BCL11A-8234	+	CCGUCGUCGGACUUGACCGUCAU	23	9945
  BCL11A-8235	+	ACCGUCGUCGGACUUGACCGUCAU	24	9946
  BCL11A-8236	+	AUAGGGCUGGGCCGGCCU	18	9947
  BCL11A-8237	+	CAUAGGGCUGGGCCGGCCU	19	9948
  BCL11A-6198	+	GCAUAGGGCUGGGCCGGCCU	20	9949
  BCL11A-8238	+	UGCAUAGGGCUGGGCCGGCCU	21	9950
  BCL11A-8239	+	UUGCAUAGGGCUGGGCCGGCCU	22	9951
  BCL11A-8240	+	UUUGCAUAGGGCUGGGCCGGCCU	23	9952
  BCL11A-8241	+	CUUUGCAUAGGGCUGGGCCGGCCU	24	9953
  BCL11A-8242	+	UCUGGAGUCUCCGAAGCU	18	9954
  BCL11A-8243	+	GUCUGGAGUCUCCGAAGCU	19	9955
  BCL11A-8244	+	UGUCUGGAGUCUCCGAAGCU	20	9956
  BCL11A-8245	+	UUGUCUGGAGUCUCCGAAGCU	21	9957
  BCL11A-8246	+	AUUGUCUGGAGUCUCCGAAGCU	22	9958
  BCL11A-8247	+	GAUUGUCUGGAGUCUCCGAAGCU	23	9959
  BCL11A-8248	+	CGAUUGUCUGGAGUCUCCGAAGCU	24	9960
  BCL11A-8249	+	UCUCGAGCUUGAUGCGCU	18	9961
  BCL11A-8250	+	UUCUCGAGCUUGAUGCGCU	19	9962
  BCL11A-8251	+	CUUCUCGAGCUUGAUGCGCU	20	9963
  BCL11A-8252	+	CCUUCUCGAGCUUGAUGCGCU	21	9964
  BCL11A-8253	+	UCCUUCUCGAGCUUGAUGCGCU	22	9965
  BCL11A-8254	+	CUCCUUCUCGAGCUUGAUGCGCU	23	9966
  BCL11A-8255	+	ACUCCUUCUCGAGCUUGAUGCGCU	24	9967
  BCL11A-8256	+	UGGACUUGACCGGGGGCU	18	9968
  BCL11A-8257	+	UUGGACUUGACCGGGGGCU	19	9969
  BCL11A-6207	+	CUUGGACUUGACCGGGGGCU	20	9970
  BCL11A-8258	+	ACUUGGACUUGACCGGGGGCU	21	9971
  BCL11A-8259	+	GACUUGGACUUGACCGGGGGCU	22	9972
  BCL11A-8260	+	UGACUUGGACUUGACCGGGGGCU	23	9973
  BCL11A-8261	+	AUGACUUGGACUUGACCGGGGGCU	24	9974
  BCL11A-8262	+	UCCCAUGGAGAGGUGGCU	18	9975
  BCL11A-8263	+	AUCCCAUGGAGAGGUGGCU	19	9976
  BCL11A-6208	+	AAUCCCAUGGAGAGGUGGCU	20	9977
  BCL11A-8264	+	GAAUCCCAUGGAGAGGUGGCU	21	9978
  BCL11A-8265	+	UGAAUCCCAUGGAGAGGUGGCU	22	9979
  BCL11A-8266	+	AUGAAUCCCAUGGAGAGGUGGCU	23	9980
  BCL11A-8267	+	UAUGAAUCCCAUGGAGAGGUGGCU	24	9981
  BCL11A-8268	+	GUGCACCACCAGGUUGCU	18	9982
  BCL11A-8269	+	GGUGCACCACCAGGUUGCU	19	9983
  BCL11A-8270	+	CGGUGCACCACCAGGUUGCU	20	9984
  BCL11A-8271	+	CCGGUGCACCACCAGGUUGCU	21	9985
  BCL11A-8272	+	GCCGGUGCACCACCAGGUUGCU	22	9986
  BCL11A-8273	+	CGCCGGUGCACCACCAGGUUGCU	23	9987
  BCL11A-8274	+	GCGCCGGUGCACCACCAGGUUGCU	24	9988
  BCL11A-8275	+	AAGCUAAGGAAGGGAUCU	18	9989
  BCL11A-8276	+	GAAGCUAAGGAAGGGAUCU	19	9990
  BCL11A-8277	+	CGAAGCUAAGGAAGGGAUCU	20	9991
  BCL11A-8278	+	CCGAAGCUAAGGAAGGGAUCU	21	9992
  BCL11A-8279	+	UCCGAAGCUAAGGAAGGGAUCU	22	9993
  BCL11A-8280	+	CUCCGAAGCUAAGGAAGGGAUCU	23	9994
  BCL11A-8281	+	UCUCCGAAGCUAAGGAAGGGAUCU	24	9995
  BCL11A-8282	+	GGCGAUUGUCUGGAGUCU	18	9996
  BCL11A-8283	+	AGGCGAUUGUCUGGAGUCU	19	9997
  BCL11A-8284	+	AAGGCGAUUGUCUGGAGUCU	20	9998
  BCL11A-8285	+	AAAGGCGAUUGUCUGGAGUCU	21	9999
  BCL11A-8286	+	AAAAGGCGAUUGUCUGGAGUCU	22	10000
  BCL11A-8287	+	CAAAAGGCGAUUGUCUGGAGUCU	23	10001
  BCL11A-8288	+	GCAAAAGGCGAUUGUCUGGAGUCU	24	10002
  BCL11A-8289	+	CCUCCUCGUCCCCGUUCU	18	10003
  BCL11A-8290	+	UCCUCCUCGUCCCCGUUCU	19	10004
  BCL11A-8291	+	UUCCUCCUCGUCCCCGUUCU	20	10005
  BCL11A-8292	+	CUUCCUCCUCGUCCCCGUUCU	21	10006
  BCL11A-8293	+	UCUUCCUCCUCGUCCCCGUUCU	22	10007
  BCL11A-8294	+	CUCUUCCUCCUCGUCCCCGUUCU	23	10008
  BCL11A-8295	+	CCUCUUCCUCCUCGUCCCCGUUCU	24	10009
  BCL11A-8296	+	AGCGCAAACUCCCGUUCU	18	10010
  BCL11A-8297	+	AAGCGCAAACUCCCGUUCU	19	10011
  BCL11A-8298	+	GAAGCGCAAACUCCCGUUCU	20	10012
  BCL11A-8299	+	AGAAGCGCAAACUCCCGUUCU	21	10013
  BCL11A-8300	+	GAGAAGCGCAAACUCCCGUUCU	22	10014
  BCL11A-8301	+	GGAGAAGCGCAAACUCCCGUUCU	23	10015
  BCL11A-8302	+	UGGAGAAGCGCAAACUCCCGUUCU	24	10016
  BCL11A-8303	+	GGGGGCUUCAAAUUUUCU	18	10017
  BCL11A-8304	+	UGGGGGCUUCAAAUUUUCU	19	10018
  BCL11A-8305	+	CUGGGGGCUUCAAAUUUUCU	20	10019
  BCL11A-8306	+	CCUGGGGGCUUCAAAUUUUCU	21	10020
  BCL11A-8307	+	CCCUGGGGGCUUCAAAUUUUCU	22	10021
  BCL11A-8308	+	CCCCUGGGGGCUUCAAAUUUUCU	23	10022
  BCL11A-8309	+	ACCCCUGGGGGCUUCAAAUUUUCU	24	10023
  BCL11A-8310	+	AAGAACCUAGAAAGAGGU	18	10024
  BCL11A-8311	+	GAAGAACCUAGAAAGAGGU	19	10025
  BCL11A-6224	+	UGAAGAACCUAGAAAGAGGU	20	10026
  BCL11A-8312	+	GUGAAGAACCUAGAAAGAGGU	21	10027
  BCL11A-8313	+	UGUGAAGAACCUAGAAAGAGGU	22	10028
  BCL11A-8314	+	GUGUGAAGAACCUAGAAAGAGGU	23	10029
  BCL11A-8315	+	UGUGUGAAGAACCUAGAAAGAGGU	24	10030
  BCL11A-8316	+	UCCAGCUCCCCGGGCGGU	18	10031
  BCL11A-8317	+	GUCCAGCUCCCCGGGCGGU	19	10032
  BCL11A-8318	+	CGUCCAGCUCCCCGGGCGGU	20	10033
  BCL11A-8319	+	CCGUCCAGCUCCCCGGGCGGU	21	10034
  BCL11A-8320	+	UCCGUCCAGCUCCCCGGGCGGU	22	10035
  BCL11A-8321	+	CUCCGUCCAGCUCCCCGGGCGGU	23	10036
  BCL11A-8322	+	CCUCCGUCCAGCUCCCCGGGCGGU	24	10037
  BCL11A-8323	+	GAUACCAACCCGCGGGGU	18	10038
  BCL11A-8324	+	GGAUACCAACCCGCGGGGU	19	10039
  BCL11A-8325	+	GGGAUACCAACCCGCGGGGU	20	10040
  BCL11A-8326	+	AGGGAUACCAACCCGCGGGGU	21	10041
  BCL11A-8327	+	AAGGGAUACCAACCCGCGGGGU	22	10042
  BCL11A-8328	+	GAAGGGAUACCAACCCGCGGGGU	23	10043
  BCL11A-8329	+	UGAAGGGAUACCAACCCGCGGGGU	24	10044
  BCL11A-8330	+	UACGCCGAAUGGGGGUGU	18	10045
  BCL11A-8331	+	CUACGCCGAAUGGGGGUGU	19	10046
  BCL11A-8332	+	ACUACGCCGAAUGGGGGUGU	20	10047
  BCL11A-8333	+	UACUACGCCGAAUGGGGGUGU	21	10048
  BCL11A-8334	+	GUACUACGCCGAAUGGGGGUGU	22	10049
  BCL11A-8335	+	GGUACUACGCCGAAUGGGGGUGU	23	10050
  BCL11A-8336	+	GGGUACUACGCCGAAUGGGGGUGU	24	10051
  BCL11A-8337	+	GAGGCAAAAGGCGAUUGU	18	10052
  BCL11A-8338	+	GGAGGCAAAAGGCGAUUGU	19	10053
  BCL11A-8339	+	AGGAGGCAAAAGGCGAUUGU	20	10054
  BCL11A-8340	+	GAGGAGGCAAAAGGCGAUUGU	21	10055
  BCL11A-8341	+	CGAGGAGGCAAAAGGCGAUUGU	22	10056
  BCL11A-8342	+	ACGAGGAGGCAAAAGGCGAUUGU	23	10057
  BCL11A-8343	+	GACGAGGAGGCAAAAGGCGAUUGU	24	10058
  BCL11A-8344	+	CAAAUUUUCUCAGAACUU	18	10059
  BCL11A-8345	+	UCAAAUUUUCUCAGAACUU	19	10060
  BCL11A-8346	+	UUCAAAUUUUCUCAGAACUU	20	10061
  BCL11A-8347	+	CUUCAAAUUUUCUCAGAACUU	21	10062
  BCL11A-8348	+	GCUUCAAAUUUUCUCAGAACUU	22	10063
  BCL11A-8349	+	GGCUUCAAAUUUUCUCAGAACUU	23	10064
  BCL11A-8350	+	GGGCUUCAAAUUUUCUCAGAACUU	24	10065
  BCL11A-8351	+	CGCUGCGUCUGCCCUCUU	18	10066
  BCL11A-8352	+	UCGCUGCGUCUGCCCUCUU	19	10067
  BCL11A-8353	+	GUCGCUGCGUCUGCCCUCUU	20	10068
  BCL11A-8354	+	UGUCGCUGCGUCUGCCCUCUU	21	10069
  BCL11A-8355	+	GUGUCGCUGCGUCUGCCCUCUU	22	10070
  BCL11A-8356	+	AGUGUCGCUGCGUCUGCCCUCUU	23	10071
  BCL11A-8357	+	AAGUGUCGCUGCGUCUGCCCUCUU	24	10072
  BCL11A-8358	+	AGUCGCUGGUGCCGGGUU	18	10073
  BCL11A-8359	+	AAGUCGCUGGUGCCGGGUU	19	10074
  BCL11A-8360	+	CAAGUCGCUGGUGCCGGGUU	20	10075
  BCL11A-8361	+	CCAAGUCGCUGGUGCCGGGUU	21	10076
  BCL11A-8362	+	ACCAAGUCGCUGGUGCCGGGUU	22	10077
  BCL11A-8363	+	CACCAAGUCGCUGGUGCCGGGUU	23	10078
  BCL11A-8364	+	CCACCAAGUCGCUGGUGCCGGGUU	24	10079
  BCL11A-8365	+	CUGCCCAGCAGCAGCUUU	18	10080
  BCL11A-8366	+	GCUGCCCAGCAGCAGCUUU	19	10081
  BCL11A-8367	+	GGCUGCCCAGCAGCAGCUUU	20	10082
  BCL11A-8368	+	GGGCUGCCCAGCAGCAGCUUU	21	10083
  BCL11A-8369	+	GGGGCUGCCCAGCAGCAGCUUU	22	10084
  BCL11A-8370	+	UGGGGCUGCCCAGCAGCAGCUUU	23	10085
  BCL11A-8371	+	CUGGGGCUGCCCAGCAGCAGCUUU	24	10086
  BCL11A-8372	-	GGCAGGCCCAGCUCAAAA	18	10087
  BCL11A-8373	-	GGGCAGGCCCAGCUCAAAA	19	10088
  BCL11A-8374	-	CGGGCAGGCCCAGCUCAAAA	20	10089
  BCL11A-8375	-	CCGGGCAGGCCCAGCUCAAAA	21	10090
  BCL11A-8376	-	CCCGGGCAGGCCCAGCUCAAAA	22	10091
  BCL11A-8377	-	GCCCGGGCAGGCCCAGCUCAAAA	23	10092
  BCL11A-8378	-	GGCCCGGGCAGGCCCAGCUCAAAA	24	10093
  BCL11A-8379	-	UAAGAAUCUACUUAGAAA	18	10094
  BCL11A-8380	-	UUAAGAAUCUACUUAGAAA	19	10095
  BCL11A-8381	-	AUUAAGAAUCUACUUAGAAA	20	10096
  BCL11A-8382	-	GAUUAAGAAUCUACUUAGAAA	21	10097
  BCL11A-8383	-	GGAUUAAGAAUCUACUUAGAAA	22	10098
  BCL11A-8384	-	UGGAUUAAGAAUCUACUUAGAAA	23	10099
  BCL11A-8385	-	AUGGAUUAAGAAUCUACUUAGAAA	24	10100
  BCL11A-8386	-	CGGGCAGGCCCAGCUCAA	18	10101
  BCL11A-8387	-	CCGGGCAGGCCCAGCUCAA	19	10102
  BCL11A-8388	-	CCCGGGCAGGCCCAGCUCAA	20	10103
  BCL11A-8389	-	GCCCGGGCAGGCCCAGCUCAA	21	10104
  BCL11A-8390	-	GGCCCGGGCAGGCCCAGCUCAA	22	10105
  BCL11A-8391	-	GGGCCCGGGCAGGCCCAGCUCAA	23	10106
  BCL11A-8392	-	CGGGCCCGGGCAGGCCCAGCUCAA	24	10107
  BCL11A-8393	-	GACGAGGAAGAGGAAGAA	18	10108
  BCL11A-8394	-	CGACGAGGAAGAGGAAGAA	19	10109
  BCL11A-3947	-	ACGACGAGGAAGAGGAAGAA	20	10110
  BCL11A-8395	-	GACGACGAGGAAGAGGAAGAA	21	10111
  BCL11A-8396	-	GGACGACGAGGAAGAGGAAGAA	22	10112
  BCL11A-8397	-	AGGACGACGAGGAAGAGGAAGAA	23	10113
  BCL11A-8398	-	GAGGACGACGAGGAAGAGGAAGAA	24	10114
  BCL11A-8399	-	CAACCUGAUCCCGGAGAA	18	10115
  BCL11A-8400	-	CCAACCUGAUCCCGGAGAA	19	10116
  BCL11A-5881	-	CCCAACCUGAUCCCGGAGAA	20	10117
  BCL11A-8401	-	CCCCAACCUGAUCCCGGAGAA	21	10118
  BCL11A-8402	-	ACCCCAACCUGAUCCCGGAGAA	22	10119
  BCL11A-8403	-	GACCCCAACCUGAUCCCGGAGAA	23	10120
  BCL11A-8404	-	CGACCCCAACCUGAUCCCGGAGAA	24	10121
  BCL11A-8405	-	GGAGCACUCCUCGGAGAA	18	10122
  BCL11A-8406	-	CGGAGCACUCCUCGGAGAA	19	10123
  BCL11A-5882	-	UCGGAGCACUCCUCGGAGAA	20	10124
  BCL11A-8407	-	GUCGGAGCACUCCUCGGAGAA	21	10125
  BCL11A-8408	-	CGUCGGAGCACUCCUCGGAGAA	22	10126
  BCL11A-8409	-	UCGUCGGAGCACUCCUCGGAGAA	23	10127
  BCL11A-8410	-	CUCGUCGGAGCACUCCUCGGAGAA	24	10128
  BCL11A-8411	-	GAGGAGGACGACGAGGAA	18	10129
  BCL11A-8412	-	AGAGGAGGACGACGAGGAA	19	10130
  BCL11A-3950	-	AAGAGGAGGACGACGAGGAA	20	10131
  BCL11A-8413	-	GAAGAGGAGGACGACGAGGAA	21	10132
  BCL11A-8414	-	GGAAGAGGAGGACGACGAGGAA	22	10133
  BCL11A-8415	-	AGGAAGAGGAGGACGACGAGGAA	23	10134
  BCL11A-8416	-	GAGGAAGAGGAGGACGACGAGGAA	24	10135
  BCL11A-8417	-	GAGGAAGAAGAGGAGGAA	18	10136
  BCL11A-8418	-	AGAGGAAGAAGAGGAGGAA	19	10137
  BCL11A-3962	-	AAGAGGAAGAAGAGGAGGAA	20	10138
  BCL11A-8419	-	GAAGAGGAAGAAGAGGAGGAA	21	10139
  BCL11A-8420	-	GGAAGAGGAAGAAGAGGAGGAA	22	10140
  BCL11A-8421	-	AGGAAGAGGAAGAAGAGGAGGAA	23	10141
  BCL11A-8422	-	GAGGAAGAGGAAGAAGAGGAGGAA	24	10142
  BCL11A-8423	-	AACGGGGACGAGGAGGAA	18	10143
  BCL11A-8424	-	GAACGGGGACGAGGAGGAA	19	10144
  BCL11A-3934	-	AGAACGGGGACGAGGAGGAA	20	10145
  BCL11A-8425	-	GAGAACGGGGACGAGGAGGAA	21	10146
  BCL11A-8426	-	GGAGAACGGGGACGAGGAGGAA	22	10147
  BCL11A-8427	-	CGGAGAACGGGGACGAGGAGGAA	23	10148
  BCL11A-8428	-	CCGGAGAACGGGGACGAGGAGGAA	24	10149
  BCL11A-8429	-	GGCGCAGCGGCACGGGAA	18	10150
  BCL11A-8430	-	GGGCGCAGCGGCACGGGAA	19	10151
  BCL11A-3857	-	GGGGCGCAGCGGCACGGGAA	20	10152
  BCL11A-8431	-	CGGGGCGCAGCGGCACGGGAA	21	10153
  BCL11A-8432	-	UCGGGGCGCAGCGGCACGGGAA	22	10154
  BCL11A-8433	-	CUCGGGGCGCAGCGGCACGGGAA	23	10155
  BCL11A-8434	-	UCUCGGGGCGCAGCGGCACGGGAA	24	10156
  BCL11A-8435	-	CGGCCGCGAUGCCCAACA	18	10157
  BCL11A-8436	-	CCGGCCGCGAUGCCCAACA	19	10158
  BCL11A-5893	-	CCCGGCCGCGAUGCCCAACA	20	10159
  BCL11A-8437	-	CCCCGGCCGCGAUGCCCAACA	21	10160
  BCL11A-8438	-	CCCCCGGCCGCGAUGCCCAACA	22	10161
  BCL11A-8439	-	GCCCCCGGCCGCGAUGCCCAACA	23	10162
  BCL11A-8440	-	UGCCCCCGGCCGCGAUGCCCAACA	24	10163
  BCL11A-8441	-	CUACUUAGAAAGCGAACA	18	10164
  BCL11A-8442	-	UCUACUUAGAAAGCGAACA	19	10165
  BCL11A-5894	-	AUCUACUUAGAAAGCGAACA	20	10166
  BCL11A-8443	-	AAUCUACUUAGAAAGCGAACA	21	10167
  BCL11A-8444	-	GAAUCUACUUAGAAAGCGAACA	22	10168
  BCL11A-8445	-	AGAAUCUACUUAGAAAGCGAACA	23	10169
  BCL11A-8446	-	AAGAAUCUACUUAGAAAGCGAACA	24	10170
  BCL11A-8447	-	CCCCUGUUUAGUCCACCA	18	10171
  BCL11A-8448	-	CCCCCUGUUUAGUCCACCA	19	10172
  BCL11A-8449	-	CCCCCCUGUUUAGUCCACCA	20	10173
  BCL11A-8450	-	CCCCCCCUGUUUAGUCCACCA	21	10174
  BCL11A-8451	-	UCCCCCCCUGUUUAGUCCACCA	22	10175
  BCL11A-8452	-	CUCCCCCCCUGUUUAGUCCACCA	23	10176
  BCL11A-8453	-	ACUCCCCCCCUGUUUAGUCCACCA	24	10177
  BCL11A-8454	-	CAUUCGGCGUAGUACCCA	18	10178
  BCL11A-8455	-	CCAUUCGGCGUAGUACCCA	19	10179
  BCL11A-8456	-	CCCAUUCGGCGUAGUACCCA	20	10180
  BCL11A-8457	-	CCCCAUUCGGCGUAGUACCCA	21	10181
  BCL11A-8458	-	CCCCCAUUCGGCGUAGUACCCA	22	10182
  BCL11A-8459	-	ACCCCCAUUCGGCGUAGUACCCA	23	10183
  BCL11A-8460	-	CACCCCCAUUCGGCGUAGUACCCA	24	10184
  BCL11A-8461	-	GGCCGAGGCCGAGGGCCA	18	10185
  BCL11A-8462	-	UGGCCGAGGCCGAGGGCCA	19	10186
  BCL11A-8463	-	CUGGCCGAGGCCGAGGGCCA	20	10187
  BCL11A-8464	-	CCUGGCCGAGGCCGAGGGCCA	21	10188
  BCL11A-8465	-	ACCUGGCCGAGGCCGAGGGCCA	22	10189
  BCL11A-8466	-	CACCUGGCCGAGGCCGAGGGCCA	23	10190
  BCL11A-8467	-	CCACCUGGCCGAGGCCGAGGGCCA	24	10191
  BCL11A-8468	-	UUUCUCUUGCAACACGCA	18	10192
  BCL11A-8469	-	GUUUCUCUUGCAACACGCA	19	10193
  BCL11A-8470	-	GGUUUCUCUUGCAACACGCA	20	10194
  BCL11A-8471	-	UGGUUUCUCUUGCAACACGCA	21	10195
  BCL11A-8472	-	AUGGUUUCUCUUGCAACACGCA	22	10196
  BCL11A-8473	-	CAUGGUUUCUCUUGCAACACGCA	23	10197
  BCL11A-8474	-	GCAUGGUUUCUCUUGCAACACGCA	24	10198
  BCL11A-8475	-	ACUUGGACCCCCACCGCA	18	10199
  BCL11A-8476	-	CACUUGGACCCCCACCGCA	19	10200
  BCL11A-8477	-	UCACUUGGACCCCCACCGCA	20	10201
  BCL11A-8478	-	AUCACUUGGACCCCCACCGCA	21	10202
  BCL11A-8479	-	CAUCACUUGGACCCCCACCGCA	22	10203
  BCL11A-8480	-	ACAUCACUUGGACCCCCACCGCA	23	10204
  BCL11A-8481	-	GACAUCACUUGGACCCCCACCGCA	24	10205
  BCL11A-8482	-	UCUCGGGGCGCAGCGGCA	18	10206
  BCL11A-8483	-	AUCUCGGGGCGCAGCGGCA	19	10207
  BCL11A-5904	-	GAUCUCGGGGCGCAGCGGCA	20	10208
  BCL11A-8484	-	GGAUCUCGGGGCGCAGCGGCA	21	10209
  BCL11A-8485	-	GGGAUCUCGGGGCGCAGCGGCA	22	10210
  BCL11A-8486	-	AGGGAUCUCGGGGCGCAGCGGCA	23	10211
  BCL11A-8487	-	GAGGGAUCUCGGGGCGCAGCGGCA	24	10212
  BCL11A-8488	-	AGACUUAGAGAGCUGGCA	18	10213
  BCL11A-8489	-	GAGACUUAGAGAGCUGGCA	19	10214
  BCL11A-5907	-	GGAGACUUAGAGAGCUGGCA	20	10215
  BCL11A-8490	-	AGGAGACUUAGAGAGCUGGCA	21	10216
  BCL11A-8491	-	UAGGAGACUUAGAGAGCUGGCA	22	10217
  BCL11A-8492	-	CUAGGAGACUUAGAGAGCUGGCA	23	10218
  BCL11A-8493	-	UCUAGGAGACUUAGAGAGCUGGCA	24	10219
  BCL11A-8494	-	GCUCCAUGCAGCACUUCA	18	10220
  BCL11A-8495	-	AGCUCCAUGCAGCACUUCA	19	10221
  BCL11A-8496	-	CAGCUCCAUGCAGCACUUCA	20	10222
  BCL11A-8497	-	UCAGCUCCAUGCAGCACUUCA	21	10223
  BCL11A-8498	-	CUCAGCUCCAUGCAGCACUUCA	22	10224
  BCL11A-8499	-	GCUCAGCUCCAUGCAGCACUUCA	23	10225
  BCL11A-8500	-	UGCUCAGCUCCAUGCAGCACUUCA	24	10226
  BCL11A-8501	-	UGGUGGCCAAGUUCAAGA	18	10227
  BCL11A-8502	-	GUGGUGGCCAAGUUCAAGA	19	10228
  BCL11A-8503	-	CGUGGUGGCCAAGUUCAAGA	20	10229
  BCL11A-8504	-	CCGUGGUGGCCAAGUUCAAGA	21	10230
  BCL11A-8505	-	UCCGUGGUGGCCAAGUUCAAGA	22	10231
  BCL11A-8506	-	GUCCGUGGUGGCCAAGUUCAAGA	23	10232
  BCL11A-8507	-	AGUCCGUGGUGGCCAAGUUCAAGA	24	10233
  BCL11A-8508	-	AGGAGGAGCUGACGGAGA	18	10234
  BCL11A-8509	-	GAGGAGGAGCUGACGGAGA	19	10235
  BCL11A-8510	-	GGAGGAGGAGCUGACGGAGA	20	10236
  BCL11A-8511	-	AGGAGGAGGAGCUGACGGAGA	21	10237
  BCL11A-8512	-	GAGGAGGAGGAGCUGACGGAGA	22	10238
  BCL11A-8513	-	GGAGGAGGAGGAGCUGACGGAGA	23	10239
  BCL11A-8514	-	AGGAGGAGGAGGAGCUGACGGAGA	24	10240
  BCL11A-8515	-	CCAACCUGAUCCCGGAGA	18	10241
  BCL11A-8516	-	CCCAACCUGAUCCCGGAGA	19	10242
  BCL11A-8517	-	CCCCAACCUGAUCCCGGAGA	20	10243
  BCL11A-8518	-	ACCCCAACCUGAUCCCGGAGA	21	10244
  BCL11A-8519	-	GACCCCAACCUGAUCCCGGAGA	22	10245
  BCL11A-8520	-	CGACCCCAACCUGAUCCCGGAGA	23	10246
  BCL11A-8521	-	ACGACCCCAACCUGAUCCCGGAGA	24	10247
  BCL11A-8522	-	CGGAGCACUCCUCGGAGA	18	10248
  BCL11A-8523	-	UCGGAGCACUCCUCGGAGA	19	10249
  BCL11A-8524	-	GUCGGAGCACUCCUCGGAGA	20	10250
  BCL11A-8525	-	CGUCGGAGCACUCCUCGGAGA	21	10251
  BCL11A-8526	-	UCGUCGGAGCACUCCUCGGAGA	22	10252
  BCL11A-8527	-	CUCGUCGGAGCACUCCUCGGAGA	23	10253
  BCL11A-8528	-	CCUCGUCGGAGCACUCCUCGGAGA	24	10254
  BCL11A-8529	-	UACCAGGAUCAGUAUCGA	18	10255
  BCL11A-8530	-	AUACCAGGAUCAGUAUCGA	19	10256
  BCL11A-8531	-	AAUACCAGGAUCAGUAUCGA	20	10257
  BCL11A-8532	-	GAAUACCAGGAUCAGUAUCGA	21	10258
  BCL11A-8533	-	AGAAUACCAGGAUCAGUAUCGA	22	10259
  BCL11A-8534	-	AAGAAUACCAGGAUCAGUAUCGA	23	10260
  BCL11A-8535	-	UAAGAAUACCAGGAUCAGUAUCGA	24	10261
  BCL11A-8536	-	UGUGUGGCAGUUUUCGGA	18	10262
  BCL11A-8537	-	AUGUGUGGCAGUUUUCGGA	19	10263
  BCL11A-5929	-	GAUGUGUGGCAGUUUUCGGA	20	10264
  BCL11A-8538	-	AGAUGUGUGGCAGUUUUCGGA	21	10265
  BCL11A-8539	-	AAGAUGUGUGGCAGUUUUCGGA	22	10266
  BCL11A-8540	-	CAAGAUGUGUGGCAGUUUUCGGA	23	10267
  BCL11A-8541	-	UCAAGAUGUGUGGCAGUUUUCGGA	24	10268
  BCL11A-8542	-	ACCGCCCGGGGAGCUGGA	18	10269
  BCL11A-8543	-	CACCGCCCGGGGAGCUGGA	19	10270
  BCL11A-5933	-	ACACCGCCCGGGGAGCUGGA	20	10271
  BCL11A-8544	-	CACACCGCCCGGGGAGCUGGA	21	10272
  BCL11A-8545	-	CCACACCGCCCGGGGAGCUGGA	22	10273
  BCL11A-8546	-	UCCACACCGCCCGGGGAGCUGGA	23	10274
  BCL11A-8547	-	CUCCACACCGCCCGGGGAGCUGGA	24	10275
  BCL11A-8548	-	AGCGGCACGGGAAGUGGA	18	10276
  BCL11A-8549	-	CAGCGGCACGGGAAGUGGA	19	10277
  BCL11A-5934	-	GCAGCGGCACGGGAAGUGGA	20	10278
  BCL11A-8550	-	CGCAGCGGCACGGGAAGUGGA	21	10279
  BCL11A-8551	-	GCGCAGCGGCACGGGAAGUGGA	22	10280
  BCL11A-8552	-	GGCGCAGCGGCACGGGAAGUGGA	23	10281
  BCL11A-8553	-	GGGCGCAGCGGCACGGGAAGUGGA	24	10282
  BCL11A-8554	-	AGGAGGAGGAGGAGCUGA	18	10283
  BCL11A-8555	-	GAGGAGGAGGAGGAGCUGA	19	10284
  BCL11A-5938	-	AGAGGAGGAGGAGGAGCUGA	20	10285
  BCL11A-8556	-	AAGAGGAGGAGGAGGAGCUGA	21	10286
  BCL11A-8557	-	GAAGAGGAGGAGGAGGAGCUGA	22	10287
  BCL11A-8558	-	GGAAGAGGAGGAGGAGGAGCUGA	23	10288
  BCL11A-8559	-	AGGAAGAGGAGGAGGAGGAGCUGA	24	10289
  BCL11A-8560	-	GGUUGAAUCCAAUGGCUA	18	10290
  BCL11A-8561	-	CGGUUGAAUCCAAUGGCUA	19	10291
  BCL11A-5944	-	GCGGUUGAAUCCAAUGGCUA	20	10292
  BCL11A-8562	-	UGCGGUUGAAUCCAAUGGCUA	21	10293
  BCL11A-8563	-	CUGCGGUUGAAUCCAAUGGCUA	22	10294
  BCL11A-8564	-	GCUGCGGUUGAAUCCAAUGGCUA	23	10295
  BCL11A-8565	-	UGCUGCGGUUGAAUCCAAUGGCUA	24	10296
  BCL11A-8566	-	AGAAUACCAGGAUCAGUA	18	10297
  BCL11A-8567	-	AAGAAUACCAGGAUCAGUA	19	10298
  BCL11A-8568	-	UAAGAAUACCAGGAUCAGUA	20	10299
  BCL11A-8569	-	CUAAGAAUACCAGGAUCAGUA	21	10300
  BCL11A-8570	-	GCUAAGAAUACCAGGAUCAGUA	22	10301
  BCL11A-8571	-	UGCUAAGAAUACCAGGAUCAGUA	23	10302
  BCL11A-8572	-	CUGCUAAGAAUACCAGGAUCAGUA	24	10303
  BCL11A-8573	-	AUUUCUCUAGGAGACUUA	18	10304
  BCL11A-8574	-	GAUUUCUCUAGGAGACUUA	19	10305
  BCL11A-8575	-	GGAUUUCUCUAGGAGACUUA	20	10306
  BCL11A-8576	-	UGGAUUUCUCUAGGAGACUUA	21	10307
  BCL11A-8577	-	AUGGAUUUCUCUAGGAGACUUA	22	10308
  BCL11A-8578	-	CAUGGAUUUCUCUAGGAGACUUA	23	10309
  BCL11A-8579	-	CCAUGGAUUUCUCUAGGAGACUUA	24	10310
  BCL11A-8580	-	CCGGCCGCGAUGCCCAAC	18	10311
  BCL11A-8581	-	CCCGGCCGCGAUGCCCAAC	19	10312
  BCL11A-8582	-	CCCCGGCCGCGAUGCCCAAC	20	10313
  BCL11A-8583	-	CCCCCGGCCGCGAUGCCCAAC	21	10314
  BCL11A-8584	-	GCCCCCGGCCGCGAUGCCCAAC	22	10315
  BCL11A-8585	-	UGCCCCCGGCCGCGAUGCCCAAC	23	10316
  BCL11A-8586	-	CUGCCCCCGGCCGCGAUGCCCAAC	24	10317
  BCL11A-8587	-	AACCUGAUCCCGGAGAAC	18	10318
  BCL11A-8588	-	CAACCUGAUCCCGGAGAAC	19	10319
  BCL11A-5948	-	CCAACCUGAUCCCGGAGAAC	20	10320
  BCL11A-8589	-	CCCAACCUGAUCCCGGAGAAC	21	10321
  BCL11A-8590	-	CCCCAACCUGAUCCCGGAGAAC	22	10322
  BCL11A-8591	-	ACCCCAACCUGAUCCCGGAGAAC	23	10323
  BCL11A-8592	-	GACCCCAACCUGAUCCCGGAGAAC	24	10324
  BCL11A-8593	-	UCUACUUAGAAAGCGAAC	18	10325
  BCL11A-8594	-	AUCUACUUAGAAAGCGAAC	19	10326
  BCL11A-8595	-	AAUCUACUUAGAAAGCGAAC	20	10327
  BCL11A-8596	-	GAAUCUACUUAGAAAGCGAAC	21	10328
  BCL11A-8597	-	AGAAUCUACUUAGAAAGCGAAC	22	10329
  BCL11A-8598	-	AAGAAUCUACUUAGAAAGCGAAC	23	10330
  BCL11A-8599	-	UAAGAAUCUACUUAGAAAGCGAAC	24	10331
  BCL11A-8600	-	GAGGCGGCGCGCCACCAC	18	10332
  BCL11A-8601	-	GGAGGCGGCGCGCCACCAC	19	10333
  BCL11A-8602	-	UGGAGGCGGCGCGCCACCAC	20	10334
  BCL11A-8603	-	CUGGAGGCGGCGCGCCACCAC	21	10335
  BCL11A-8604	-	CCUGGAGGCGGCGCGCCACCAC	22	10336
  BCL11A-8605	-	GCCUGGAGGCGGCGCGCCACCAC	23	10337
  BCL11A-8606	-	AGCCUGGAGGCGGCGCGCCACCAC	24	10338
  BCL11A-8607	-	GUGCACCGGCGCAGCCAC	18	10339
  BCL11A-8608	-	GGUGCACCGGCGCAGCCAC	19	10340
  BCL11A-8609	-	UGGUGCACCGGCGCAGCCAC	20	10341
  BCL11A-8610	-	GUGGUGCACCGGCGCAGCCAC	21	10342
  BCL11A-8611	-	GGUGGUGCACCGGCGCAGCCAC	22	10343
  BCL11A-8612	-	UGGUGGUGCACCGGCGCAGCCAC	23	10344
  BCL11A-8613	-	CUGGUGGUGCACCGGCGCAGCCAC	24	10345
  BCL11A-8614	-	AGCAAGCUGAAGCGCCAC	18	10346
  BCL11A-8615	-	CAGCAAGCUGAAGCGCCAC	19	10347
  BCL11A-8616	-	CCAGCAAGCUGAAGCGCCAC	20	10348
  BCL11A-8617	-	GCCAGCAAGCUGAAGCGCCAC	21	10349
  BCL11A-8618	-	GGCCAGCAAGCUGAAGCGCCAC	22	10350
  BCL11A-8619	-	AGGCCAGCAAGCUGAAGCGCCAC	23	10351
  BCL11A-8620	-	CAGGCCAGCAAGCUGAAGCGCCAC	24	10352
  BCL11A-8621	-	GCCGAGGCCGAGGGCCAC	18	10353
  BCL11A-8622	-	GGCCGAGGCCGAGGGCCAC	19	10354
  BCL11A-5951	-	UGGCCGAGGCCGAGGGCCAC	20	10355
  BCL11A-8623	-	CUGGCCGAGGCCGAGGGCCAC	21	10356
  BCL11A-8624	-	CCUGGCCGAGGCCGAGGGCCAC	22	10357
  BCL11A-8625	-	ACCUGGCCGAGGCCGAGGGCCAC	23	10358
  BCL11A-8626	-	CACCUGGCCGAGGCCGAGGGCCAC	24	10359
  BCL11A-8627	-	CUCGGGGCGCAGCGGCAC	18	10360
  BCL11A-8628	-	UCUCGGGGCGCAGCGGCAC	19	10361
  BCL11A-5953	-	AUCUCGGGGCGCAGCGGCAC	20	10362
  BCL11A-8629	-	GAUCUCGGGGCGCAGCGGCAC	21	10363
  BCL11A-8630	-	GGAUCUCGGGGCGCAGCGGCAC	22	10364
  BCL11A-8631	-	GGGAUCUCGGGGCGCAGCGGCAC	23	10365
  BCL11A-8632	-	AGGGAUCUCGGGGCGCAGCGGCAC	24	10366
  BCL11A-8633	-	CCACCACCGAGACAUCAC	18	10367
  BCL11A-8634	-	UCCACCACCGAGACAUCAC	19	10368
  BCL11A-8635	-	GUCCACCACCGAGACAUCAC	20	10369
  BCL11A-8636	-	AGUCCACCACCGAGACAUCAC	21	10370
  BCL11A-8637	-	UAGUCCACCACCGAGACAUCAC	22	10371
  BCL11A-8638	-	UUAGUCCACCACCGAGACAUCAC	23	10372
  BCL11A-8639	-	UUUAGUCCACCACCGAGACAUCAC	24	10373
  BCL11A-8640	-	GAGGAAGAGGAGGACGAC	18	10374
  BCL11A-8641	-	GGAGGAAGAGGAGGACGAC	19	10375
  BCL11A-3949	-	AGGAGGAAGAGGAGGACGAC	20	10376
  BCL11A-8642	-	GAGGAGGAAGAGGAGGACGAC	21	10377
  BCL11A-8643	-	CGAGGAGGAAGAGGAGGACGAC	22	10378
  BCL11A-8644	-	ACGAGGAGGAAGAGGAGGACGAC	23	10379
  BCL11A-8645	-	GACGAGGAGGAAGAGGAGGACGAC	24	10380
  BCL11A-8646	-	GUCGUGGGCGUGGGCGAC	18	10381
  BCL11A-8647	-	GGUCGUGGGCGUGGGCGAC	19	10382
  BCL11A-8648	-	CGGUCGUGGGCGUGGGCGAC	20	10383
  BCL11A-8649	-	GCGGUCGUGGGCGUGGGCGAC	21	10384
  BCL11A-8650	-	CGCGGUCGUGGGCGUGGGCGAC	22	10385
  BCL11A-8651	-	GCGCGGUCGUGGGCGUGGGCGAC	23	10386
  BCL11A-8652	-	GGCGCGGUCGUGGGCGUGGGCGAC	24	10387
  BCL11A-8653	-	AUCCCGGAGAACGGGGAC	18	10388
  BCL11A-8654	-	GAUCCCGGAGAACGGGGAC	19	10389
  BCL11A-8655	-	UGAUCCCGGAGAACGGGGAC	20	10390
  BCL11A-8656	-	CUGAUCCCGGAGAACGGGGAC	21	10391
  BCL11A-8657	-	CCUGAUCCCGGAGAACGGGGAC	22	10392
  BCL11A-8658	-	ACCUGAUCCCGGAGAACGGGGAC	23	10393
  BCL11A-8659	-	AACCUGAUCCCGGAGAACGGGGAC	24	10394
  BCL11A-8660	-	UGGAGGCGGCGCGCCACC	18	10395
  BCL11A-8661	-	CUGGAGGCGGCGCGCCACC	19	10396
  BCL11A-8662	-	CCUGGAGGCGGCGCGCCACC	20	10397
  BCL11A-8663	-	GCCUGGAGGCGGCGCGCCACC	21	10398
  BCL11A-8664	-	AGCCUGGAGGCGGCGCGCCACC	22	10399
  BCL11A-8665	-	GAGCCUGGAGGCGGCGCGCCACC	23	10400
  BCL11A-8666	-	UGAGCCUGGAGGCGGCGCGCCACC	24	10401
  BCL11A-8667	-	CCCAUUCGGCGUAGUACC	18	10402
  BCL11A-8668	-	CCCCAUUCGGCGUAGUACC	19	10403
  BCL11A-8669	-	CCCCCAUUCGGCGUAGUACC	20	10404
  BCL11A-8670	-	ACCCCCAUUCGGCGUAGUACC	21	10405
  BCL11A-8671	-	CACCCCCAUUCGGCGUAGUACC	22	10406
  BCL11A-8672	-	ACACCCCCAUUCGGCGUAGUACC	23	10407
  BCL11A-8673	-	CACACCCCCAUUCGGCGUAGUACC	24	10408
  BCL11A-8674	-	GAGAAAAUUUGAAGCCCC	18	10409
  BCL11A-8675	-	UGAGAAAAUUUGAAGCCCC	19	10410
  BCL11A-8676	-	CUGAGAAAAUUUGAAGCCCC	20	10411
  BCL11A-8677	-	UCUGAGAAAAUUUGAAGCCCC	21	10412
  BCL11A-8678	-	UUCUGAGAAAAUUUGAAGCCCC	22	10413
  BCL11A-8679	-	GUUCUGAGAAAAUUUGAAGCCCC	23	10414
  BCL11A-8680	-	AGUUCUGAGAAAAUUUGAAGCCCC	24	10415
  BCL11A-8681	-	CGCUUCUCCACACCGCCC	18	10416
  BCL11A-8682	-	GCGCUUCUCCACACCGCCC	19	10417
  BCL11A-5976	-	UGCGCUUCUCCACACCGCCC	20	10418
  BCL11A-8683	-	UUGCGCUUCUCCACACCGCCC	21	10419
  BCL11A-8684	-	UUUGCGCUUCUCCACACCGCCC	22	10420
  BCL11A-8685	-	GUUUGCGCUUCUCCACACCGCCC	23	10421
  BCL11A-8686	-	AGUUUGCGCUUCUCCACACCGCCC	24	10422
  BCL11A-8687	-	UCUCCACCGCCAGCUCCC	18	10423
  BCL11A-8688	-	CUCUCCACCGCCAGCUCCC	19	10424
  BCL11A-5982	-	UCUCUCCACCGCCAGCUCCC	20	10425
  BCL11A-8689	-	GUCUCUCCACCGCCAGCUCCC	21	10426
  BCL11A-8690	-	GGUCUCUCCACCGCCAGCUCCC	22	10427
  BCL11A-8691	-	CGGUCUCUCCACCGCCAGCUCCC	23	10428
  BCL11A-8692	-	ACGGUCUCUCCACCGCCAGCUCCC	24	10429
  BCL11A-8693	-	ACGGCUUCGGGCUGAGCC	18	10430
  BCL11A-8694	-	UACGGCUUCGGGCUGAGCC	19	10431
  BCL11A-5986	-	CUACGGCUUCGGGCUGAGCC	20	10432
  BCL11A-8695	-	ACUACGGCUUCGGGCUGAGCC	21	10433
  BCL11A-8696	-	GACUACGGCUUCGGGCUGAGCC	22	10434
  BCL11A-8697	-	GGACUACGGCUUCGGGCUGAGCC	23	10435
  BCL11A-8698	-	UGGACUACGGCUUCGGGCUGAGCC	24	10436
  BCL11A-8699	-	GCGCUUCUCCACACCGCC	18	10437
  BCL11A-8700	-	UGCGCUUCUCCACACCGCC	19	10438
  BCL11A-5987	-	UUGCGCUUCUCCACACCGCC	20	10439
  BCL11A-8701	-	UUUGCGCUUCUCCACACCGCC	21	10440
  BCL11A-8702	-	GUUUGCGCUUCUCCACACCGCC	22	10441
  BCL11A-8703	-	AGUUUGCGCUUCUCCACACCGCC	23	10442
  BCL11A-8704	-	GAGUUUGCGCUUCUCCACACCGCC	24	10443
  BCL11A-8705	-	CCCACCGCAUAGAGCGCC	18	10444
  BCL11A-8706	-	CCCCACCGCAUAGAGCGCC	19	10445
  BCL11A-5988	-	CCCCCACCGCAUAGAGCGCC	20	10446
  BCL11A-8707	-	ACCCCCACCGCAUAGAGCGCC	21	10447
  BCL11A-8708	-	GACCCCCACCGCAUAGAGCGCC	22	10448
  BCL11A-8709	-	GGACCCCCACCGCAUAGAGCGCC	23	10449
  BCL11A-8710	-	UGGACCCCCACCGCAUAGAGCGCC	24	10450
  BCL11A-8711	-	GGCCACCUGGCCGAGGCC	18	10451
  BCL11A-8712	-	CGGCCACCUGGCCGAGGCC	19	10452
  BCL11A-8713	-	GCGGCCACCUGGCCGAGGCC	20	10453
  BCL11A-8714	-	CGCGGCCACCUGGCCGAGGCC	21	10454
  BCL11A-8715	-	GCGCGGCCACCUGGCCGAGGCC	22	10455
  BCL11A-8716	-	AGCGCGGCCACCUGGCCGAGGCC	23	10456
  BCL11A-8717	-	AAGCGCGGCCACCUGGCCGAGGCC	24	10457
  BCL11A-8718	-	UCCCCGGGCGAGUCGGCC	18	10458
  BCL11A-8719	-	CUCCCCGGGCGAGUCGGCC	19	10459
  BCL11A-8720	-	GCUCCCCGGGCGAGUCGGCC	20	10460
  BCL11A-8721	-	UGCUCCCCGGGCGAGUCGGCC	21	10461
  BCL11A-8722	-	CUGCUCCCCGGGCGAGUCGGCC	22	10462
  BCL11A-8723	-	GCUGCUCCCCGGGCGAGUCGGCC	23	10463
  BCL11A-8724	-	GGCUGCUCCCCGGGCGAGUCGGCC	24	10464
  BCL11A-8725	-	ACGACCCCAACCUGAUCC	18	10465
  BCL11A-8726	-	AACGACCCCAACCUGAUCC	19	10466
  BCL11A-6004	-	GAACGACCCCAACCUGAUCC	20	10467
  BCL11A-8727	-	AGAACGACCCCAACCUGAUCC	21	10468
  BCL11A-8728	-	GAGAACGACCCCAACCUGAUCC	22	10469
  BCL11A-8729	-	CGAGAACGACCCCAACCUGAUCC	23	10470
  BCL11A-8730	-	GCGAGAACGACCCCAACCUGAUCC	24	10471
  BCL11A-8731	-	UCCUCGUCGGAGCACUCC	18	10472
  BCL11A-8732	-	CUCCUCGUCGGAGCACUCC	19	10473
  BCL11A-8733	-	CCUCCUCGUCGGAGCACUCC	20	10474
  BCL11A-8734	-	GCCUCCUCGUCGGAGCACUCC	21	10475
  BCL11A-8735	-	UGCCUCCUCGUCGGAGCACUCC	22	10476
  BCL11A-8736	-	UUGCCUCCUCGUCGGAGCACUCC	23	10477
  BCL11A-8737	-	UUUGCCUCCUCGUCGGAGCACUCC	24	10478
  BCL11A-8738	-	CUCUCCACCGCCAGCUCC	18	10479
  BCL11A-8739	-	UCUCUCCACCGCCAGCUCC	19	10480
  BCL11A-8740	-	GUCUCUCCACCGCCAGCUCC	20	10481
  BCL11A-8741	-	GGUCUCUCCACCGCCAGCUCC	21	10482
  BCL11A-8742	-	CGGUCUCUCCACCGCCAGCUCC	22	10483
  BCL11A-8743	-	ACGGUCUCUCCACCGCCAGCUCC	23	10484
  BCL11A-8744	-	GACGGUCUCUCCACCGCCAGCUCC	24	10485
  BCL11A-8745	-	AAUGGCCGCGGCUGCUCC	18	10486
  BCL11A-8746	-	UAAUGGCCGCGGCUGCUCC	19	10487
  BCL11A-8747	-	UUAAUGGCCGCGGCUGCUCC	20	10488
  BCL11A-8748	-	GUUAAUGGCCGCGGCUGCUCC	21	10489
  BCL11A-8749	-	UGUUAAUGGCCGCGGCUGCUCC	22	10490
  BCL11A-8750	-	CUGUUAAUGGCCGCGGCUGCUCC	23	10491
  BCL11A-8751	-	ACUGUUAAUGGCCGCGGCUGCUCC	24	10492
  BCL11A-8752	-	CUUCCCAGCCACCUCUCC	18	10493
  BCL11A-8753	-	CCUUCCCAGCCACCUCUCC	19	10494
  BCL11A-8754	-	UCCUUCCCAGCCACCUCUCC	20	10495
  BCL11A-8755	-	GUCCUUCCCAGCCACCUCUCC	21	10496
  BCL11A-8756	-	UGUCCUUCCCAGCCACCUCUCC	22	10497
  BCL11A-8757	-	AUGUCCUUCCCAGCCACCUCUCC	23	10498
  BCL11A-8758	-	AAUGUCCUUCCCAGCCACCUCUCC	24	10499
  BCL11A-8759	-	UCUCUAAGCGCAUCAAGC	18	10500
  BCL11A-8760	-	UUCUCUAAGCGCAUCAAGC	19	10501
  BCL11A-8761	-	CUUCUCUAAGCGCAUCAAGC	20	10502
  BCL11A-8762	-	CCUUCUCUAAGCGCAUCAAGC	21	10503
  BCL11A-8763	-	CCCUUCUCUAAGCGCAUCAAGC	22	10504
  BCL11A-8764	-	CCCCUUCUCUAAGCGCAUCAAGC	23	10505
  BCL11A-8765	-	GCCCCUUCUCUAAGCGCAUCAAGC	24	10506
  BCL11A-8766	-	CAGUUUUCGGAUGGAAGC	18	10507
  BCL11A-8767	-	GCAGUUUUCGGAUGGAAGC	19	10508
  BCL11A-8768	-	GGCAGUUUUCGGAUGGAAGC	20	10509
  BCL11A-8769	-	UGGCAGUUUUCGGAUGGAAGC	21	10510
  BCL11A-8770	-	GUGGCAGUUUUCGGAUGGAAGC	22	10511
  BCL11A-8771	-	UGUGGCAGUUUUCGGAUGGAAGC	23	10512
  BCL11A-8772	-	GUGUGGCAGUUUUCGGAUGGAAGC	24	10513
  BCL11A-8773	-	GUGGCCAAGUUCAAGAGC	18	10514
  BCL11A-8774	-	GGUGGCCAAGUUCAAGAGC	19	10515
  BCL11A-8775	-	UGGUGGCCAAGUUCAAGAGC	20	10516
  BCL11A-8776	-	GUGGUGGCCAAGUUCAAGAGC	21	10517
  BCL11A-8777	-	CGUGGUGGCCAAGUUCAAGAGC	22	10518
  BCL11A-8778	-	CCGUGGUGGCCAAGUUCAAGAGC	23	10519
  BCL11A-8779	-	UCCGUGGUGGCCAAGUUCAAGAGC	24	10520
  BCL11A-8780	-	GAGGAGCUGACGGAGAGC	18	10521
  BCL11A-8781	-	GGAGGAGCUGACGGAGAGC	19	10522
  BCL11A-8782	-	AGGAGGAGCUGACGGAGAGC	20	10523
  BCL11A-8783	-	GAGGAGGAGCUGACGGAGAGC	21	10524
  BCL11A-8784	-	GGAGGAGGAGCUGACGGAGAGC	22	10525
  BCL11A-8785	-	AGGAGGAGGAGCUGACGGAGAGC	23	10526
  BCL11A-8786	-	GAGGAGGAGGAGCUGACGGAGAGC	24	10527
  BCL11A-8787	-	UACGGCUUCGGGCUGAGC	18	10528
  BCL11A-8788	-	CUACGGCUUCGGGCUGAGC	19	10529
  BCL11A-8789	-	ACUACGGCUUCGGGCUGAGC	20	10530
  BCL11A-8790	-	GACUACGGCUUCGGGCUGAGC	21	10531
  BCL11A-8791	-	GGACUACGGCUUCGGGCUGAGC	22	10532
  BCL11A-8792	-	UGGACUACGGCUUCGGGCUGAGC	23	10533
  BCL11A-8793	-	GUGGACUACGGCUUCGGGCUGAGC	24	10534
  BCL11A-8794	-	UGCGCUUCUCCACACCGC	18	10535
  BCL11A-8795	-	UUGCGCUUCUCCACACCGC	19	10536
  BCL11A-8796	-	UUUGCGCUUCUCCACACCGC	20	10537
  BCL11A-8797	-	GUUUGCGCUUCUCCACACCGC	21	10538
  BCL11A-8798	-	AGUUUGCGCUUCUCCACACCGC	22	10539
  BCL11A-8799	-	GAGUUUGCGCUUCUCCACACCGC	23	10540
  BCL11A-8800	-	GGAGUUUGCGCUUCUCCACACCGC	24	10541
  BCL11A-8801	-	CCCCACCGCAUAGAGCGC	18	10542
  BCL11A-8802	-	CCCCCACCGCAUAGAGCGC	19	10543
  BCL11A-8803	-	ACCCCCACCGCAUAGAGCGC	20	10544
  BCL11A-8804	-	GACCCCCACCGCAUAGAGCGC	21	10545
  BCL11A-8805	-	GGACCCCCACCGCAUAGAGCGC	22	10546
  BCL11A-8806	-	UGGACCCCCACCGCAUAGAGCGC	23	10547
  BCL11A-8807	-	UUGGACCCCCACCGCAUAGAGCGC	24	10548
  BCL11A-8808	-	AUCUCGGGGCGCAGCGGC	18	10549
  BCL11A-8809	-	GAUCUCGGGGCGCAGCGGC	19	10550
  BCL11A-8810	-	GGAUCUCGGGGCGCAGCGGC	20	10551
  BCL11A-8811	-	GGGAUCUCGGGGCGCAGCGGC	21	10552
  BCL11A-8812	-	AGGGAUCUCGGGGCGCAGCGGC	22	10553
  BCL11A-8813	-	GAGGGAUCUCGGGGCGCAGCGGC	23	10554
  BCL11A-8814	-	GGAGGGAUCUCGGGGCGCAGCGGC	24	10555
  BCL11A-8815	-	CGGCGCAGCCACACGGGC	18	10556
  BCL11A-8816	-	CCGGCGCAGCCACACGGGC	19	10557
  BCL11A-3804	-	ACCGGCGCAGCCACACGGGC	20	10558
  BCL11A-8817	-	CACCGGCGCAGCCACACGGGC	21	10559
  BCL11A-8818	-	GCACCGGCGCAGCCACACGGGC	22	10560
  BCL11A-8819	-	UGCACCGGCGCAGCCACACGGGC	23	10561
  BCL11A-8820	-	GUGCACCGGCGCAGCCACACGGGC	24	10562
  BCL11A-8821	-	CAUAUUAGUGGUCCGGGC	18	10563
  BCL11A-8822	-	CCAUAUUAGUGGUCCGGGC	19	10564
  BCL11A-8823	-	CCCAUAUUAGUGGUCCGGGC	20	10565
  BCL11A-8824	-	CCCCAUAUUAGUGGUCCGGGC	21	10566
  BCL11A-8825	-	GCCCCAUAUUAGUGGUCCGGGC	22	10567
  BCL11A-8826	-	CGCCCCAUAUUAGUGGUCCGGGC	23	10568
  BCL11A-8827	-	ACGCCCCAUAUUAGUGGUCCGGGC	24	10569
  BCL11A-8828	-	UUCCACCAGGUCCUGGGC	18	10570
  BCL11A-8829	-	CUUCCACCAGGUCCUGGGC	19	10571
  BCL11A-8830	-	CCUUCCACCAGGUCCUGGGC	20	10572
  BCL11A-8831	-	GCCUUCCACCAGGUCCUGGGC	21	10573
  BCL11A-8832	-	GGCCUUCCACCAGGUCCUGGGC	22	10574
  BCL11A-8833	-	AGGCCUUCCACCAGGUCCUGGGC	23	10575
  BCL11A-8834	-	GAGGCCUUCCACCAGGUCCUGGGC	24	10576
  BCL11A-8835	-	CGGGGCGCGGUCGUGGGC	18	10577
  BCL11A-8836	-	GCGGGGCGCGGUCGUGGGC	19	10578
  BCL11A-8837	-	CGCGGGGCGCGGUCGUGGGC	20	10579
  BCL11A-8838	-	UCGCGGGGCGCGGUCGUGGGC	21	10580
  BCL11A-8839	-	CUCGCGGGGCGCGGUCGUGGGC	22	10581
  BCL11A-8840	-	GCUCGCGGGGCGCGGUCGUGGGC	23	10582
  BCL11A-8841	-	AGCUCGCGGGGCGCGGUCGUGGGC	24	10583
  BCL11A-8842	-	GAGACUUAGAGAGCUGGC	18	10584
  BCL11A-8843	-	GGAGACUUAGAGAGCUGGC	19	10585
  BCL11A-6037	-	AGGAGACUUAGAGAGCUGGC	20	10586
  BCL11A-8844	-	UAGGAGACUUAGAGAGCUGGC	21	10587
  BCL11A-8845	-	CUAGGAGACUUAGAGAGCUGGC	22	10588
  BCL11A-8846	-	UCUAGGAGACUUAGAGAGCUGGC	23	10589
  BCL11A-8847	-	CUCUAGGAGACUUAGAGAGCUGGC	24	10590
  BCL11A-8848	-	GAGCUGGACGGAGGGAUC	18	10591
  BCL11A-8849	-	GGAGCUGGACGGAGGGAUC	19	10592
  BCL11A-8850	-	GGGAGCUGGACGGAGGGAUC	20	10593
  BCL11A-8851	-	GGGGAGCUGGACGGAGGGAUC	21	10594
  BCL11A-8852	-	CGGGGAGCUGGACGGAGGGAUC	22	10595
  BCL11A-8853	-	CCGGGGAGCUGGACGGAGGGAUC	23	10596
  BCL11A-8854	-	CCCGGGGAGCUGGACGGAGGGAUC	24	10597
  BCL11A-8855	-	AACGACCCCAACCUGAUC	18	10598
  BCL11A-8856	-	GAACGACCCCAACCUGAUC	19	10599
  BCL11A-8857	-	AGAACGACCCCAACCUGAUC	20	10600
  BCL11A-8858	-	GAGAACGACCCCAACCUGAUC	21	10601
  BCL11A-8859	-	CGAGAACGACCCCAACCUGAUC	22	10602
  BCL11A-8860	-	GCGAGAACGACCCCAACCUGAUC	23	10603
  BCL11A-8861	-	AGCGAGAACGACCCCAACCUGAUC	24	10604
  BCL11A-8862	-	AAUACCAGGAUCAGUAUC	18	10605
  BCL11A-8863	-	GAAUACCAGGAUCAGUAUC	19	10606
  BCL11A-8864	-	AGAAUACCAGGAUCAGUAUC	20	10607
  BCL11A-8865	-	AAGAAUACCAGGAUCAGUAUC	21	10608
  BCL11A-8866	-	UAAGAAUACCAGGAUCAGUAUC	22	10609
  BCL11A-8867	-	CUAAGAAUACCAGGAUCAGUAUC	23	10610
  BCL11A-8868	-	GCUAAGAAUACCAGGAUCAGUAUC	24	10611
  BCL11A-8869	-	CCCGGGCGAGUCGGCCUC	18	10612
  BCL11A-8870	-	CCCCGGGCGAGUCGGCCUC	19	10613
  BCL11A-6047	-	UCCCCGGGCGAGUCGGCCUC	20	10614
  BCL11A-8871	-	CUCCCCGGGCGAGUCGGCCUC	21	10615
  BCL11A-8872	-	GCUCCCCGGGCGAGUCGGCCUC	22	10616
  BCL11A-8873	-	UGCUCCCCGGGCGAGUCGGCCUC	23	10617
  BCL11A-8874	-	CUGCUCCCCGGGCGAGUCGGCCUC	24	10618
  BCL11A-8875	-	UCUAAGCGCAUCAAGCUC	18	10619
  BCL11A-8876	-	CUCUAAGCGCAUCAAGCUC	19	10620
  BCL11A-8877	-	UCUCUAAGCGCAUCAAGCUC	20	10621
  BCL11A-8878	-	UUCUCUAAGCGCAUCAAGCUC	21	10622
  BCL11A-8879	-	CUUCUCUAAGCGCAUCAAGCUC	22	10623
  BCL11A-8880	-	CCUUCUCUAAGCGCAUCAAGCUC	23	10624
  BCL11A-8881	-	CCCUUCUCUAAGCGCAUCAAGCUC	24	10625
  BCL11A-8882	-	GUUUUCGGAUGGAAGCUC	18	10626
  BCL11A-8883	-	AGUUUUCGGAUGGAAGCUC	19	10627
  BCL11A-8884	-	CAGUUUUCGGAUGGAAGCUC	20	10628
  BCL11A-8885	-	GCAGUUUUCGGAUGGAAGCUC	21	10629
  BCL11A-8886	-	GGCAGUUUUCGGAUGGAAGCUC	22	10630
  BCL11A-8887	-	UGGCAGUUUUCGGAUGGAAGCUC	23	10631
  BCL11A-8888	-	GUGGCAGUUUUCGGAUGGAAGCUC	24	10632
  BCL11A-8889	-	CCACCACGAGAACAGCUC	18	10633
  BCL11A-8890	-	GCCACCACGAGAACAGCUC	19	10634
  BCL11A-8891	-	CGCCACCACGAGAACAGCUC	20	10635
  BCL11A-8892	-	GCGCCACCACGAGAACAGCUC	21	10636
  BCL11A-8893	-	CGCGCCACCACGAGAACAGCUC	22	10637
  BCL11A-8894	-	GCGCGCCACCACGAGAACAGCUC	23	10638
  BCL11A-8895	-	GGCGCGCCACCACGAGAACAGCUC	24	10639
  BCL11A-8896	-	UCCCGCCAUGGAUUUCUC	18	10640
  BCL11A-8897	-	CUCCCGCCAUGGAUUUCUC	19	10641
  BCL11A-8898	-	CCUCCCGCCAUGGAUUUCUC	20	10642
  BCL11A-8899	-	GCCUCCCGCCAUGGAUUUCUC	21	10643
  BCL11A-8900	-	AGCCUCCCGCCAUGGAUUUCUC	22	10644
  BCL11A-8901	-	GAGCCUCCCGCCAUGGAUUUCUC	23	10645
  BCL11A-8902	-	GGAGCCUCCCGCCAUGGAUUUCUC	24	10646
  BCL11A-8903	-	GAGGCCUUCCACCAGGUC	18	10647
  BCL11A-8904	-	CGAGGCCUUCCACCAGGUC	19	10648
  BCL11A-8905	-	GCGAGGCCUUCCACCAGGUC	20	10649
  BCL11A-8906	-	AGCGAGGCCUUCCACCAGGUC	21	10650
  BCL11A-8907	-	CAGCGAGGCCUUCCACCAGGUC	22	10651
  BCL11A-8908	-	UCAGCGAGGCCUUCCACCAGGUC	23	10652
  BCL11A-8909	-	UUCAGCGAGGCCUUCCACCAGGUC	24	10653
  BCL11A-8910	-	AGCUCGCGGGGCGCGGUC	18	10654
  BCL11A-8911	-	CAGCUCGCGGGGCGCGGUC	19	10655
  BCL11A-8912	-	ACAGCUCGCGGGGCGCGGUC	20	10656
  BCL11A-8913	-	AACAGCUCGCGGGGCGCGGUC	21	10657
  BCL11A-8914	-	GAACAGCUCGCGGGGCGCGGUC	22	10658
  BCL11A-8915	-	AGAACAGCUCGCGGGGCGCGGUC	23	10659
  BCL11A-8916	-	GAGAACAGCUCGCGGGGCGCGGUC	24	10660
  BCL11A-8917	-	UACUGUGGGAAAGUCUUC	18	10661
  BCL11A-8918	-	GUACUGUGGGAAAGUCUUC	19	10662
  BCL11A-8919	-	AGUACUGUGGGAAAGUCUUC	20	10663
  BCL11A-8920	-	GAGUACUGUGGGAAAGUCUUC	21	10664
  BCL11A-8921	-	UGAGUACUGUGGGAAAGUCUUC	22	10665
  BCL11A-8922	-	GUGAGUACUGUGGGAAAGUCUUC	23	10666
  BCL11A-8923	-	UGUGAGUACUGUGGGAAAGUCUUC	24	10667
  BCL11A-8924	-	UCCGUGGUGGCCAAGUUC	18	10668
  BCL11A-8925	-	GUCCGUGGUGGCCAAGUUC	19	10669
  BCL11A-8926	-	AGUCCGUGGUGGCCAAGUUC	20	10670
  BCL11A-8927	-	AAGUCCGUGGUGGCCAAGUUC	21	10671
  BCL11A-8928	-	CAAGUCCGUGGUGGCCAAGUUC	22	10672
  BCL11A-8929	-	UCAAGUCCGUGGUGGCCAAGUUC	23	10673
  BCL11A-8930	-	CUCAAGUCCGUGGUGGCCAAGUUC	24	10674
  BCL11A-6826	-	AUUAUUUUGCAGGUAAAG	18	10675
  BCL11A-6827	-	UAUUAUUUUGCAGGUAAAG	19	10676
  BCL11A-6828	-	GUAUUAUUUUGCAGGUAAAG	20	10677
  BCL11A-8931	-	UGCACCCAGGCCAGCAAG	18	10678
  BCL11A-8932	-	GUGCACCCAGGCCAGCAAG	19	10679
  BCL11A-8933	-	CGUGCACCCAGGCCAGCAAG	20	10680
  BCL11A-8934	-	GCGUGCACCCAGGCCAGCAAG	21	10681
  BCL11A-8935	-	CGCGUGCACCCAGGCCAGCAAG	22	10682
  BCL11A-8936	-	ACGCGUGCACCCAGGCCAGCAAG	23	10683
  BCL11A-8937	-	CACGCGUGCACCCAGGCCAGCAAG	24	10684
  BCL11A-8938	-	ACGAGGAAGAGGAAGAAG	18	10685
  BCL11A-8939	-	GACGAGGAAGAGGAAGAAG	19	10686
  BCL11A-3449	-	CGACGAGGAAGAGGAAGAAG	20	10687
  BCL11A-8940	-	ACGACGAGGAAGAGGAAGAAG	21	10688
  BCL11A-8941	-	GACGACGAGGAAGAGGAAGAAG	22	10689
  BCL11A-8942	-	GGACGACGAGGAAGAGGAAGAAG	23	10690
  BCL11A-8943	-	AGGACGACGAGGAAGAGGAAGAAG	24	10691
  BCL11A-8944	-	ACGACGAGGAAGAGGAAG	18	10692
  BCL11A-8945	-	GACGACGAGGAAGAGGAAG	19	10693
  BCL11A-3959	-	GGACGACGAGGAAGAGGAAG	20	10694
  BCL11A-8946	-	AGGACGACGAGGAAGAGGAAG	21	10695
  BCL11A-8947	-	GAGGACGACGAGGAAGAGGAAG	22	10696
  BCL11A-8948	-	GGAGGACGACGAGGAAGAGGAAG	23	10697
  BCL11A-8949	-	AGGAGGACGACGAGGAAGAGGAAG	24	10698
  BCL11A-8950	-	AGGAGGACGACGAGGAAG	18	10699
  BCL11A-8951	-	GAGGAGGACGACGAGGAAG	19	10700
  BCL11A-3448	-	AGAGGAGGACGACGAGGAAG	20	10701
  BCL11A-8952	-	AAGAGGAGGACGACGAGGAAG	21	10702
  BCL11A-8953	-	GAAGAGGAGGACGACGAGGAAG	22	10703
  BCL11A-8954	-	GGAAGAGGAGGACGACGAGGAAG	23	10704
  BCL11A-8955	-	AGGAAGAGGAGGACGACGAGGAAG	24	10705
  BCL11A-8956	-	AGGAAGAAGAGGAGGAAG	18	10706
  BCL11A-8957	-	GAGGAAGAAGAGGAGGAAG	19	10707
  BCL11A-3453	-	AGAGGAAGAAGAGGAGGAAG	20	10708
  BCL11A-8958	-	AAGAGGAAGAAGAGGAGGAAG	21	10709
  BCL11A-8959	-	GAAGAGGAAGAAGAGGAGGAAG	22	10710
  BCL11A-8960	-	GGAAGAGGAAGAAGAGGAGGAAG	23	10711
  BCL11A-8961	-	AGGAAGAGGAAGAAGAGGAGGAAG	24	10712
  BCL11A-8962	-	ACGGGGACGAGGAGGAAG	18	10713
  BCL11A-8963	-	AACGGGGACGAGGAGGAAG	19	10714
  BCL11A-3441	-	GAACGGGGACGAGGAGGAAG	20	10715
  BCL11A-8964	-	AGAACGGGGACGAGGAGGAAG	21	10716
  BCL11A-8965	-	GAGAACGGGGACGAGGAGGAAG	22	10717
  BCL11A-8966	-	GGAGAACGGGGACGAGGAGGAAG	23	10718
  BCL11A-8967	-	CGGAGAACGGGGACGAGGAGGAAG	24	10719
  BCL11A-8968	-	GCGCAGCGGCACGGGAAG	18	10720
  BCL11A-8969	-	GGCGCAGCGGCACGGGAAG	19	10721
  BCL11A-3376	-	GGGCGCAGCGGCACGGGAAG	20	10722
  BCL11A-8970	-	GGGGCGCAGCGGCACGGGAAG	21	10723
  BCL11A-8971	-	CGGGGCGCAGCGGCACGGGAAG	22	10724
  BCL11A-8972	-	UCGGGGCGCAGCGGCACGGGAAG	23	10725
  BCL11A-8973	-	CUCGGGGCGCAGCGGCACGGGAAG	24	10726
  BCL11A-8974	-	AGGCUUCCGGCCUGGCAG	18	10727
  BCL11A-8975	-	GAGGCUUCCGGCCUGGCAG	19	10728
  BCL11A-8976	-	AGAGGCUUCCGGCCUGGCAG	20	10729
  BCL11A-8977	-	GAGAGGCUUCCGGCCUGGCAG	21	10730
  BCL11A-8978	-	AGAGAGGCUUCCGGCCUGGCAG	22	10731
  BCL11A-8979	-	GAGAGAGGCUUCCGGCCUGGCAG	23	10732
  BCL11A-8980	-	CGAGAGAGGCUUCCGGCCUGGCAG	24	10733
  BCL11A-8981	-	GAGGAAGAGGAAGAAGAG	18	10734
  BCL11A-8982	-	CGAGGAAGAGGAAGAAGAG	19	10735
  BCL11A-3948	-	ACGAGGAAGAGGAAGAAGAG	20	10736
  BCL11A-8983	-	GACGAGGAAGAGGAAGAAGAG	21	10737
  BCL11A-8984	-	CGACGAGGAAGAGGAAGAAGAG	22	10738
  BCL11A-8985	-	ACGACGAGGAAGAGGAAGAAGAG	23	10739
  BCL11A-8986	-	GACGACGAGGAAGAGGAAGAAGAG	24	10740
  BCL11A-8987	-	GAAGAAGAGGAGGAAGAG	18	10741
  BCL11A-8988	-	GGAAGAAGAGGAGGAAGAG	19	10742
  BCL11A-3961	-	AGGAAGAAGAGGAGGAAGAG	20	10743
  BCL11A-8989	-	GAGGAAGAAGAGGAGGAAGAG	21	10744
  BCL11A-8990	-	AGAGGAAGAAGAGGAGGAAGAG	22	10745
  BCL11A-8991	-	AAGAGGAAGAAGAGGAGGAAGAG	23	10746
  BCL11A-8992	-	GAAGAGGAAGAAGAGGAGGAAGAG	24	10747
  BCL11A-8993	-	GGGGACGAGGAGGAAGAG	18	10748
  BCL11A-8994	-	CGGGGACGAGGAGGAAGAG	19	10749
  BCL11A-3945	-	ACGGGGACGAGGAGGAAGAG	20	10750
  BCL11A-8995	-	AACGGGGACGAGGAGGAAGAG	21	10751
  BCL11A-8996	-	GAACGGGGACGAGGAGGAAGAG	22	10752
  BCL11A-8997	-	AGAACGGGGACGAGGAGGAAGAG	23	10753
  BCL11A-8998	-	GAGAACGGGGACGAGGAGGAAGAG	24	10754
  BCL11A-8999	-	CCGGAGAACGGGGACGAG	18	10755
  BCL11A-9000	-	CCCGGAGAACGGGGACGAG	19	10756
  BCL11A-9001	-	UCCCGGAGAACGGGGACGAG	20	10757
  BCL11A-9002	-	AUCCCGGAGAACGGGGACGAG	21	10758
  BCL11A-9003	-	GAUCCCGGAGAACGGGGACGAG	22	10759
  BCL11A-9004	-	UGAUCCCGGAGAACGGGGACGAG	23	10760
  BCL11A-9005	-	CUGAUCCCGGAGAACGGGGACGAG	24	10761
  BCL11A-9006	-	GACUCGGUGGCCGGCGAG	18	10762
  BCL11A-9007	-	AGACUCGGUGGCCGGCGAG	19	10763
  BCL11A-9008	-	AAGACUCGGUGGCCGGCGAG	20	10764
  BCL11A-9009	-	GAAGACUCGGUGGCCGGCGAG	21	10765
  BCL11A-9010	-	CGAAGACUCGGUGGCCGGCGAG	22	10766
  BCL11A-9011	-	ACGAAGACUCGGUGGCCGGCGAG	23	10767
  BCL11A-9012	-	GACGAAGACUCGGUGGCCGGCGAG	24	10768
  BCL11A-9013	-	AAGCGCAUCAAGCUCGAG	18	10769
  BCL11A-9014	-	UAAGCGCAUCAAGCUCGAG	19	10770
  BCL11A-9015	-	CUAAGCGCAUCAAGCUCGAG	20	10771
  BCL11A-9016	-	UCUAAGCGCAUCAAGCUCGAG	21	10772
  BCL11A-9017	-	CUCUAAGCGCAUCAAGCUCGAG	22	10773
  BCL11A-9018	-	UCUCUAAGCGCAUCAAGCUCGAG	23	10774
  BCL11A-9019	-	UUCUCUAAGCGCAUCAAGCUCGAG	24	10775
  BCL11A-9020	-	GAAGAGGAGGAAGAGGAG	18	10776
  BCL11A-9021	-	AGAAGAGGAGGAAGAGGAG	19	10777
  BCL11A-3964	-	AAGAAGAGGAGGAAGAGGAG	20	10778
  BCL11A-9022	-	GAAGAAGAGGAGGAAGAGGAG	21	10779
  BCL11A-9023	-	GGAAGAAGAGGAGGAAGAGGAG	22	10780
  BCL11A-9024	-	AGGAAGAAGAGGAGGAAGAGGAG	23	10781
  BCL11A-9025	-	GAGGAAGAAGAGGAGGAAGAGGAG	24	10782
  BCL11A-9026	-	GAGGAGGAAGAGGAGGAG	18	10783
  BCL11A-9027	-	AGAGGAGGAAGAGGAGGAG	19	10784
  BCL11A-3965	-	AAGAGGAGGAAGAGGAGGAG	20	10785
  BCL11A-9028	-	GAAGAGGAGGAAGAGGAGGAG	21	10786
  BCL11A-9029	-	AGAAGAGGAGGAAGAGGAGGAG	22	10787
  BCL11A-9030	-	AAGAAGAGGAGGAAGAGGAGGAG	23	10788
  BCL11A-9031	-	GAAGAAGAGGAGGAAGAGGAGGAG	24	10789
  BCL11A-9032	-	UCCACACCGCCCGGGGAG	18	10790
  BCL11A-9033	-	CUCCACACCGCCCGGGGAG	19	10791
  BCL11A-9034	-	UCUCCACACCGCCCGGGGAG	20	10792
  BCL11A-9035	-	UUCUCCACACCGCCCGGGGAG	21	10793
  BCL11A-9036	-	CUUCUCCACACCGCCCGGGGAG	22	10794
  BCL11A-9037	-	GCUUCUCCACACCGCCCGGGGAG	23	10795
  BCL11A-9038	-	CGCUUCUCCACACCGCCCGGGGAG	24	10796
  BCL11A-9039	-	GCCGCGAUGCCCAACACG	18	10797
  BCL11A-9040	-	GGCCGCGAUGCCCAACACG	19	10798
  BCL11A-9041	-	CGGCCGCGAUGCCCAACACG	20	10799
  BCL11A-9042	-	CCGGCCGCGAUGCCCAACACG	21	10800
  BCL11A-9043	-	CCCGGCCGCGAUGCCCAACACG	22	10801
  BCL11A-9044	-	CCCCGGCCGCGAUGCCCAACACG	23	10802
  BCL11A-9045	-	CCCCCGGCCGCGAUGCCCAACACG	24	10803
  BCL11A-9046	-	AGGAAGAGGAGGACGACG	18	10804
  BCL11A-9047	-	GAGGAAGAGGAGGACGACG	19	10805
  BCL11A-3450	-	GGAGGAAGAGGAGGACGACG	20	10806
  BCL11A-9048	-	AGGAGGAAGAGGAGGACGACG	21	10807
  BCL11A-9049	-	GAGGAGGAAGAGGAGGACGACG	22	10808
  BCL11A-9050	-	CGAGGAGGAAGAGGAGGACGACG	23	10809
  BCL11A-9051	-	ACGAGGAGGAAGAGGAGGACGACG	24	10810
  BCL11A-9052	-	AGGAGGAAGAGGAGGACG	18	10811
  BCL11A-9053	-	GAGGAGGAAGAGGAGGACG	19	10812
  BCL11A-3953	-	CGAGGAGGAAGAGGAGGACG	20	10813
  BCL11A-9054	-	ACGAGGAGGAAGAGGAGGACG	21	10814
  BCL11A-9055	-	GACGAGGAGGAAGAGGAGGACG	22	10815
  BCL11A-9056	-	GGACGAGGAGGAAGAGGAGGACG	23	10816
  BCL11A-9057	-	GGGACGAGGAGGAAGAGGAGGACG	24	10817
  BCL11A-9058	-	UCCCGGAGAACGGGGACG	18	10818
  BCL11A-9059	-	AUCCCGGAGAACGGGGACG	19	10819
  BCL11A-6081	-	GAUCCCGGAGAACGGGGACG	20	10820
  BCL11A-9060	-	UGAUCCCGGAGAACGGGGACG	21	10821
  BCL11A-9061	-	CUGAUCCCGGAGAACGGGGACG	22	10822
  BCL11A-9062	-	CCUGAUCCCGGAGAACGGGGACG	23	10823
  BCL11A-9063	-	ACCUGAUCCCGGAGAACGGGGACG	24	10824
  BCL11A-9064	-	CGCCCGGGGAGCUGGACG	18	10825
  BCL11A-9065	-	CCGCCCGGGGAGCUGGACG	19	10826
  BCL11A-9066	-	ACCGCCCGGGGAGCUGGACG	20	10827
  BCL11A-9067	-	CACCGCCCGGGGAGCUGGACG	21	10828
  BCL11A-9068	-	ACACCGCCCGGGGAGCUGGACG	22	10829
  BCL11A-9069	-	CACACCGCCCGGGGAGCUGGACG	23	10830
  BCL11A-9070	-	CCACACCGCCCGGGGAGCUGGACG	24	10831
  BCL11A-9071	-	GAGGAGGAGGAGCUGACG	18	10832
  BCL11A-9072	-	GGAGGAGGAGGAGCUGACG	19	10833
  BCL11A-9073	-	AGGAGGAGGAGGAGCUGACG	20	10834
  BCL11A-9074	-	GAGGAGGAGGAGGAGCUGACG	21	10835
  BCL11A-9075	-	AGAGGAGGAGGAGGAGCUGACG	22	10836
  BCL11A-9076	-	AAGAGGAGGAGGAGGAGCUGACG	23	10837
  BCL11A-9077	-	GAAGAGGAGGAGGAGGAGCUGACG	24	10838
  BCL11A-9078	-	GCUUCUCCACACCGCCCG	18	10839
  BCL11A-9079	-	CGCUUCUCCACACCGCCCG	19	10840
  BCL11A-6087	-	GCGCUUCUCCACACCGCCCG	20	10841
  BCL11A-9080	-	UGCGCUUCUCCACACCGCCCG	21	10842
  BCL11A-9081	-	UUGCGCUUCUCCACACCGCCCG	22	10843
  BCL11A-9082	-	UUUGCGCUUCUCCACACCGCCCG	23	10844
  BCL11A-9083	-	GUUUGCGCUUCUCCACACCGCCCG	24	10845
  BCL11A-9084	-	GACCCCAACCUGAUCCCG	18	10846
  BCL11A-9085	-	CGACCCCAACCUGAUCCCG	19	10847
  BCL11A-9086	-	ACGACCCCAACCUGAUCCCG	20	10848
  BCL11A-9087	-	AACGACCCCAACCUGAUCCCG	21	10849
  BCL11A-9088	-	GAACGACCCCAACCUGAUCCCG	22	10850
  BCL11A-9089	-	AGAACGACCCCAACCUGAUCCCG	23	10851
  BCL11A-9090	-	GAGAACGACCCCAACCUGAUCCCG	24	10852
  BCL11A-9091	-	CGGUCGUGGGCGUGGGCG	18	10853
  BCL11A-9092	-	GCGGUCGUGGGCGUGGGCG	19	10854
  BCL11A-9093	-	CGCGGUCGUGGGCGUGGGCG	20	10855
  BCL11A-9094	-	GCGCGGUCGUGGGCGUGGGCG	21	10856
  BCL11A-9095	-	GGCGCGGUCGUGGGCGUGGGCG	22	10857
  BCL11A-9096	-	GGGCGCGGUCGUGGGCGUGGGCG	23	10858
  BCL11A-9097	-	GGGGCGCGGUCGUGGGCGUGGGCG	24	10859
  BCL11A-9098	-	GCCACAGGGACACUUGCG	18	10860
  BCL11A-9099	-	GGCCACAGGGACACUUGCG	19	10861
  BCL11A-9100	-	GGGCCACAGGGACACUUGCG	20	10862
  BCL11A-9101	-	AGGGCCACAGGGACACUUGCG	21	10863
  BCL11A-9102	-	GAGGGCCACAGGGACACUUGCG	22	10864
  BCL11A-9103	-	CGAGGGCCACAGGGACACUUGCG	23	10865
  BCL11A-9104	-	CCGAGGGCCACAGGGACACUUGCG	24	10866
  BCL11A-9105	-	CCGGGCGAGUCGGCCUCG	18	10867
  BCL11A-9106	-	CCCGGGCGAGUCGGCCUCG	19	10868
  BCL11A-6106	-	CCCCGGGCGAGUCGGCCUCG	20	10869
  BCL11A-9107	-	UCCCCGGGCGAGUCGGCCUCG	21	10870
  BCL11A-9108	-	CUCCCCGGGCGAGUCGGCCUCG	22	10871
  BCL11A-9109	-	GCUCCCCGGGCGAGUCGGCCUCG	23	10872
  BCL11A-9110	-	UGCUCCCCGGGCGAGUCGGCCUCG	24	10873
  BCL11A-9111	-	UCGUCGGAGCACUCCUCG	18	10874
  BCL11A-9112	-	CUCGUCGGAGCACUCCUCG	19	10875
  BCL11A-9113	-	CCUCGUCGGAGCACUCCUCG	20	10876
  BCL11A-9114	-	UCCUCGUCGGAGCACUCCUCG	21	10877
  BCL11A-9115	-	CUCCUCGUCGGAGCACUCCUCG	22	10878
  BCL11A-9116	-	CCUCCUCGUCGGAGCACUCCUCG	23	10879
  BCL11A-9117	-	GCCUCCUCGUCGGAGCACUCCUCG	24	10880
  BCL11A-9118	-	UCGCCUUUUGCCUCCUCG	18	10881
  BCL11A-9119	-	AUCGCCUUUUGCCUCCUCG	19	10882
  BCL11A-9120	-	AAUCGCCUUUUGCCUCCUCG	20	10883
  BCL11A-9121	-	CAAUCGCCUUUUGCCUCCUCG	21	10884
  BCL11A-9122	-	ACAAUCGCCUUUUGCCUCCUCG	22	10885
  BCL11A-9123	-	GACAAUCGCCUUUUGCCUCCUCG	23	10886
  BCL11A-9124	-	AGACAAUCGCCUUUUGCCUCCUCG	24	10887
  BCL11A-9125	-	CACCACGAGAACAGCUCG	18	10888
  BCL11A-9126	-	CCACCACGAGAACAGCUCG	19	10889
  BCL11A-6107	-	GCCACCACGAGAACAGCUCG	20	10890
  BCL11A-9127	-	CGCCACCACGAGAACAGCUCG	21	10891
  BCL11A-9128	-	GCGCCACCACGAGAACAGCUCG	22	10892
  BCL11A-9129	-	CGCGCCACCACGAGAACAGCUCG	23	10893
  BCL11A-9130	-	GCGCGCCACCACGAGAACAGCUCG	24	10894
  BCL11A-9131	-	CUGGGCAGCCCCAGCUCG	18	10895
  BCL11A-9132	-	GCUGGGCAGCCCCAGCUCG	19	10896
  BCL11A-9133	-	UGCUGGGCAGCCCCAGCUCG	20	10897
  BCL11A-9134	-	CUGCUGGGCAGCCCCAGCUCG	21	10898
  BCL11A-9135	-	GCUGCUGGGCAGCCCCAGCUCG	22	10899
  BCL11A-9136	-	UGCUGCUGGGCAGCCCCAGCUCG	23	10900
  BCL11A-9137	-	CUGCUGCUGGGCAGCCCCAGCUCG	24	10901
  BCL11A-9138	-	AGGAAGAGGAAGAAGAGG	18	10902
  BCL11A-9139	-	GAGGAAGAGGAAGAAGAGG	19	10903
  BCL11A-3451	-	CGAGGAAGAGGAAGAAGAGG	20	10904
  BCL11A-9140	-	ACGAGGAAGAGGAAGAAGAGG	21	10905
  BCL11A-9141	-	GACGAGGAAGAGGAAGAAGAGG	22	10906
  BCL11A-9142	-	CGACGAGGAAGAGGAAGAAGAGG	23	10907
  BCL11A-9143	-	ACGACGAGGAAGAGGAAGAAGAGG	24	10908
  BCL11A-9144	-	AGGACGACGAGGAAGAGG	18	10909
  BCL11A-9145	-	GAGGACGACGAGGAAGAGG	19	10910
  BCL11A-3957	-	GGAGGACGACGAGGAAGAGG	20	10911
  BCL11A-9146	-	AGGAGGACGACGAGGAAGAGG	21	10912
  BCL11A-9147	-	GAGGAGGACGACGAGGAAGAGG	22	10913
  BCL11A-9148	-	AGAGGAGGACGACGAGGAAGAGG	23	10914
  BCL11A-9149	-	AAGAGGAGGACGACGAGGAAGAGG	24	10915
  BCL11A-9150	-	AAGAAGAGGAGGAAGAGG	18	10916
  BCL11A-9151	-	GAAGAAGAGGAGGAAGAGG	19	10917
  BCL11A-3452	-	GGAAGAAGAGGAGGAAGAGG	20	10918
  BCL11A-9152	-	AGGAAGAAGAGGAGGAAGAGG	21	10919
  BCL11A-9153	-	GAGGAAGAAGAGGAGGAAGAGG	22	10920
  BCL11A-9154	-	AGAGGAAGAAGAGGAGGAAGAGG	23	10921
  BCL11A-9155	-	AAGAGGAAGAAGAGGAGGAAGAGG	24	10922
  BCL11A-9156	-	CUGACGGAGAGCGAGAGG	18	10923
  BCL11A-9157	-	GCUGACGGAGAGCGAGAGG	19	10924
  BCL11A-9158	-	AGCUGACGGAGAGCGAGAGG	20	10925
  BCL11A-9159	-	GAGCUGACGGAGAGCGAGAGG	21	10926
  BCL11A-9160	-	GGAGCUGACGGAGAGCGAGAGG	22	10927
  BCL11A-9161	-	AGGAGCUGACGGAGAGCGAGAGG	23	10928
  BCL11A-9162	-	GAGGAGCUGACGGAGAGCGAGAGG	24	10929
  BCL11A-9163	-	AAGAGGAGGACGACGAGG	18	10930
  BCL11A-9164	-	GAAGAGGAGGACGACGAGG	19	10931
  BCL11A-3960	-	GGAAGAGGAGGACGACGAGG	20	10932
  BCL11A-9165	-	AGGAAGAGGAGGACGACGAGG	21	10933
  BCL11A-9166	-	GAGGAAGAGGAGGACGACGAGG	22	10934
  BCL11A-9167	-	GGAGGAAGAGGAGGACGACGAGG	23	10935
  BCL11A-9168	-	AGGAGGAAGAGGAGGACGACGAGG	24	10936
  BCL11A-9169	-	CGGAGAACGGGGACGAGG	18	10937
  BCL11A-9170	-	CCGGAGAACGGGGACGAGG	19	10938
  BCL11A-3330	-	CCCGGAGAACGGGGACGAGG	20	10939
  BCL11A-9171	-	UCCCGGAGAACGGGGACGAGG	21	10940
  BCL11A-9172	-	AUCCCGGAGAACGGGGACGAGG	22	10941
  BCL11A-9173	-	GAUCCCGGAGAACGGGGACGAGG	23	10942
  BCL11A-9174	-	UGAUCCCGGAGAACGGGGACGAGG	24	10943
  BCL11A-9175	-	GCGGCCACCUGGCCGAGG	18	10944
  BCL11A-9176	-	CGCGGCCACCUGGCCGAGG	19	10945
  BCL11A-9177	-	GCGCGGCCACCUGGCCGAGG	20	10946
  BCL11A-9178	-	AGCGCGGCCACCUGGCCGAGG	21	10947
  BCL11A-9179	-	AAGCGCGGCCACCUGGCCGAGG	22	10948
  BCL11A-9180	-	UAAGCGCGGCCACCUGGCCGAGG	23	10949
  BCL11A-9181	-	AUAAGCGCGGCCACCUGGCCGAGG	24	10950
  BCL11A-9182	-	AAGAGGAAGAAGAGGAGG	18	10951
  BCL11A-9183	-	GAAGAGGAAGAAGAGGAGG	19	10952
  BCL11A-3963	-	GGAAGAGGAAGAAGAGGAGG	20	10953
  BCL11A-9184	-	AGGAAGAGGAAGAAGAGGAGG	21	10954
  BCL11A-9185	-	GAGGAAGAGGAAGAAGAGGAGG	22	10955
  BCL11A-9186	-	CGAGGAAGAGGAAGAAGAGGAGG	23	10956
  BCL11A-9187	-	ACGAGGAAGAGGAAGAAGAGGAGG	24	10957
  BCL11A-9188	-	AAGAGGAGGAAGAGGAGG	18	10958
  BCL11A-9189	-	GAAGAGGAGGAAGAGGAGG	19	10959
  BCL11A-3454	-	AGAAGAGGAGGAAGAGGAGG	20	10960
  BCL11A-9190	-	AAGAAGAGGAGGAAGAGGAGG	21	10961
  BCL11A-9191	-	GAAGAAGAGGAGGAAGAGGAGG	22	10962
  BCL11A-9192	-	GGAAGAAGAGGAGGAAGAGGAGG	23	10963
  BCL11A-9193	-	AGGAAGAAGAGGAGGAAGAGGAGG	24	10964
  BCL11A-9194	-	AGAACGGGGACGAGGAGG	18	10965
  BCL11A-9195	-	GAGAACGGGGACGAGGAGG	19	10966
  BCL11A-3918	-	GGAGAACGGGGACGAGGAGG	20	10967
  BCL11A-9196	-	CGGAGAACGGGGACGAGGAGG	21	10968
  BCL11A-9197	-	CCGGAGAACGGGGACGAGGAGG	22	10969
  BCL11A-9198	-	CCCGGAGAACGGGGACGAGGAGG	23	10970
  BCL11A-9199	-	UCCCGGAGAACGGGGACGAGGAGG	24	10971
  BCL11A-9200	-	AGGAGGAAGAGGAGGAGG	18	10972
  BCL11A-9201	-	GAGGAGGAAGAGGAGGAGG	19	10973
  BCL11A-3455	-	AGAGGAGGAAGAGGAGGAGG	20	10974
  BCL11A-9202	-	AAGAGGAGGAAGAGGAGGAGG	21	10975
  BCL11A-9203	-	GAAGAGGAGGAAGAGGAGGAGG	22	10976
  BCL11A-9204	-	AGAAGAGGAGGAAGAGGAGGAGG	23	10977
  BCL11A-9205	-	AAGAAGAGGAGGAAGAGGAGGAGG	24	10978
  BCL11A-9206	-	ACCGGCGCAGCCACACGG	18	10979
  BCL11A-9207	-	CACCGGCGCAGCCACACGG	19	10980
  BCL11A-3764	-	GCACCGGCGCAGCCACACGG	20	10981
  BCL11A-9208	-	UGCACCGGCGCAGCCACACGG	21	10982
  BCL11A-9209	-	GUGCACCGGCGCAGCCACACGG	22	10983
  BCL11A-9210	-	GGUGCACCGGCGCAGCCACACGG	23	10984
  BCL11A-9211	-	UGGUGCACCGGCGCAGCCACACGG	24	10985
  BCL11A-9212	-	UAGAGCGCCUGGGGGCGG	18	10986
  BCL11A-9213	-	AUAGAGCGCCUGGGGGCGG	19	10987
  BCL11A-9214	-	CAUAGAGCGCCUGGGGGCGG	20	10988
  BCL11A-9215	-	GCAUAGAGCGCCUGGGGGCGG	21	10989
  BCL11A-9216	-	CGCAUAGAGCGCCUGGGGGCGG	22	10990
  BCL11A-9217	-	CCGCAUAGAGCGCCUGGGGGCGG	23	10991
  BCL11A-9218	-	ACCGCAUAGAGCGCCUGGGGGCGG	24	10992
  BCL11A-9219	-	AUGUGUGGCAGUUUUCGG	18	10993
  BCL11A-9220	-	GAUGUGUGGCAGUUUUCGG	19	10994
  BCL11A-9221	-	AGAUGUGUGGCAGUUUUCGG	20	10995
  BCL11A-9222	-	AAGAUGUGUGGCAGUUUUCGG	21	10996
  BCL11A-9223	-	CAAGAUGUGUGGCAGUUUUCGG	22	10997
  BCL11A-9224	-	UCAAGAUGUGUGGCAGUUUUCGG	23	10998
  BCL11A-9225	-	CUCAAGAUGUGUGGCAGUUUUCGG	24	10999
  BCL11A-9226	-	AAUUUGAAGCCCCCAGGG	18	11000
  BCL11A-9227	-	AAAUUUGAAGCCCCCAGGG	19	11001
  BCL11A-9228	-	AAAAUUUGAAGCCCCCAGGG	20	11002
  BCL11A-9229	-	GAAAAUUUGAAGCCCCCAGGG	21	11003
  BCL11A-9230	-	AGAAAAUUUGAAGCCCCCAGGG	22	11004
  BCL11A-9231	-	GAGAAAAUUUGAAGCCCCCAGGG	23	11005
  BCL11A-9232	-	UGAGAAAAUUUGAAGCCCCCAGGG	24	11006
  BCL11A-9233	-	GUGGACUACGGCUUCGGG	18	11007
  BCL11A-9234	-	GGUGGACUACGGCUUCGGG	19	11008
  BCL11A-9235	-	GGGUGGACUACGGCUUCGGG	20	11009
  BCL11A-9236	-	AGGGUGGACUACGGCUUCGGG	21	11010
  BCL11A-9237	-	GAGGGUGGACUACGGCUUCGGG	22	11011
  BCL11A-9238	-	AGAGGGUGGACUACGGCUUCGGG	23	11012
  BCL11A-9239	-	GAGAGGGUGGACUACGGCUUCGGG	24	11013
  BCL11A-9240	-	UGAUCCCGGAGAACGGGG	18	11014
  BCL11A-9241	-	CUGAUCCCGGAGAACGGGG	19	11015
  BCL11A-9242	-	CCUGAUCCCGGAGAACGGGG	20	11016
  BCL11A-9243	-	ACCUGAUCCCGGAGAACGGGG	21	11017
  BCL11A-9244	-	AACCUGAUCCCGGAGAACGGGG	22	11018
  BCL11A-9245	-	CAACCUGAUCCCGGAGAACGGGG	23	11019
  BCL11A-9246	-	CCAACCUGAUCCCGGAGAACGGGG	24	11020
  BCL11A-9247	-	GCAUAGAGCGCCUGGGGG	18	11021
  BCL11A-9248	-	CGCAUAGAGCGCCUGGGGG	19	11022
  BCL11A-6143	-	CCGCAUAGAGCGCCUGGGGG	20	11023
  BCL11A-9249	-	ACCGCAUAGAGCGCCUGGGGG	21	11024
  BCL11A-9250	-	CACCGCAUAGAGCGCCUGGGGG	22	11025
  BCL11A-9251	-	CCACCGCAUAGAGCGCCUGGGGG	23	11026
  BCL11A-9252	-	CCCACCGCAUAGAGCGCCUGGGGG	24	11027
  BCL11A-9253	-	CGCAUAGAGCGCCUGGGG	18	11028
  BCL11A-9254	-	CCGCAUAGAGCGCCUGGGG	19	11029
  BCL11A-9255	-	ACCGCAUAGAGCGCCUGGGG	20	11030
  BCL11A-9256	-	CACCGCAUAGAGCGCCUGGGG	21	11031
  BCL11A-9257	-	CCACCGCAUAGAGCGCCUGGGG	22	11032
  BCL11A-9258	-	CCCACCGCAUAGAGCGCCUGGGG	23	11033
  BCL11A-9259	-	CCCCACCGCAUAGAGCGCCUGGGG	24	11034
  BCL11A-9260	-	AUAAGCGCGGCCACCUGG	18	11035
  BCL11A-9261	-	CAUAAGCGCGGCCACCUGG	19	11036
  BCL11A-9262	-	GCAUAAGCGCGGCCACCUGG	20	11037
  BCL11A-9263	-	AGCAUAAGCGCGGCCACCUGG	21	11038
  BCL11A-9264	-	AAGCAUAAGCGCGGCCACCUGG	22	11039
  BCL11A-9265	-	GAAGCAUAAGCGCGGCCACCUGG	23	11040
  BCL11A-9266	-	AGAAGCAUAAGCGCGGCCACCUGG	24	11041
  BCL11A-9267	-	GAGAGGCUUCCGGCCUGG	18	11042
  BCL11A-9268	-	AGAGAGGCUUCCGGCCUGG	19	11043
  BCL11A-9269	-	GAGAGAGGCUUCCGGCCUGG	20	11044
  BCL11A-9270	-	CGAGAGAGGCUUCCGGCCUGG	21	11045
  BCL11A-9271	-	UCGAGAGAGGCUUCCGGCCUGG	22	11046
  BCL11A-9272	-	AUCGAGAGAGGCUUCCGGCCUGG	23	11047
  BCL11A-9273	-	UAUCGAGAGAGGCUUCCGGCCUGG	24	11048
  BCL11A-9274	-	CCUUCCACCAGGUCCUGG	18	11049
  BCL11A-9275	-	GCCUUCCACCAGGUCCUGG	19	11050
  BCL11A-9276	-	GGCCUUCCACCAGGUCCUGG	20	11051
  BCL11A-9277	-	AGGCCUUCCACCAGGUCCUGG	21	11052
  BCL11A-9278	-	GAGGCCUUCCACCAGGUCCUGG	22	11053
  BCL11A-9279	-	CGAGGCCUUCCACCAGGUCCUGG	23	11054
  BCL11A-9280	-	GCGAGGCCUUCCACCAGGUCCUGG	24	11055
  BCL11A-9281	-	GGAGACUUAGAGAGCUGG	18	11056
  BCL11A-9282	-	AGGAGACUUAGAGAGCUGG	19	11057
  BCL11A-9283	-	UAGGAGACUUAGAGAGCUGG	20	11058
  BCL11A-9284	-	CUAGGAGACUUAGAGAGCUGG	21	11059
  BCL11A-9285	-	UCUAGGAGACUUAGAGAGCUGG	22	11060
  BCL11A-9286	-	CUCUAGGAGACUUAGAGAGCUGG	23	11061
  BCL11A-9287	-	UCUCUAGGAGACUUAGAGAGCUGG	24	11062
  BCL11A-9288	-	CACCGCCCGGGGAGCUGG	18	11063
  BCL11A-9289	-	ACACCGCCCGGGGAGCUGG	19	11064
  BCL11A-9290	-	CACACCGCCCGGGGAGCUGG	20	11065
  BCL11A-9291	-	CCACACCGCCCGGGGAGCUGG	21	11066
  BCL11A-9292	-	UCCACACCGCCCGGGGAGCUGG	22	11067
  BCL11A-9293	-	CUCCACACCGCCCGGGGAGCUGG	23	11068
  BCL11A-9294	-	UCUCCACACCGCCCGGGGAGCUGG	24	11069
  BCL11A-9295	-	CAGCGGCACGGGAAGUGG	18	11070
  BCL11A-9296	-	GCAGCGGCACGGGAAGUGG	19	11071
  BCL11A-6157	-	CGCAGCGGCACGGGAAGUGG	20	11072
  BCL11A-9297	-	GCGCAGCGGCACGGGAAGUGG	21	11073
  BCL11A-9298	-	GGCGCAGCGGCACGGGAAGUGG	22	11074
  BCL11A-9299	-	GGGCGCAGCGGCACGGGAAGUGG	23	11075
  BCL11A-9300	-	GGGGCGCAGCGGCACGGGAAGUGG	24	11076
  BCL11A-9301	-	GCCCUGCCCGACGUCAUG	18	11077
  BCL11A-9302	-	CGCCCUGCCCGACGUCAUG	19	11078
  BCL11A-9303	-	GCGCCCUGCCCGACGUCAUG	20	11079
  BCL11A-9304	-	CGCGCCCUGCCCGACGUCAUG	21	11080
  BCL11A-9305	-	CCGCGCCCUGCCCGACGUCAUG	22	11081
  BCL11A-9306	-	GCCGCGCCCUGCCCGACGUCAUG	23	11082
  BCL11A-9307	-	AGCCGCGCCCUGCCCGACGUCAUG	24	11083
  BCL11A-9308	-	CGACACUUGUGAGUACUG	18	11084
  BCL11A-9309	-	GCGACACUUGUGAGUACUG	19	11085
  BCL11A-6169	-	AGCGACACUUGUGAGUACUG	20	11086
  BCL11A-9310	-	CAGCGACACUUGUGAGUACUG	21	11087
  BCL11A-9311	-	GCAGCGACACUUGUGAGUACUG	22	11088
  BCL11A-9312	-	CGCAGCGACACUUGUGAGUACUG	23	11089
  BCL11A-9313	-	ACGCAGCGACACUUGUGAGUACUG	24	11090
  BCL11A-9314	-	GAGGAGGAGGAGGAGCUG	18	11091
  BCL11A-9315	-	AGAGGAGGAGGAGGAGCUG	19	11092
  BCL11A-9316	-	AAGAGGAGGAGGAGGAGCUG	20	11093
  BCL11A-9317	-	GAAGAGGAGGAGGAGGAGCUG	21	11094
  BCL11A-9318	-	GGAAGAGGAGGAGGAGGAGCUG	22	11095
  BCL11A-9319	-	AGGAAGAGGAGGAGGAGGAGCUG	23	11096
  BCL11A-9320	-	GAGGAAGAGGAGGAGGAGGAGCUG	24	11097
  BCL11A-9321	-	CUGUCCAAAAAGCUGCUG	18	11098
  BCL11A-9322	-	CCUGUCCAAAAAGCUGCUG	19	11099
  BCL11A-9323	-	GCCUGUCCAAAAAGCUGCUG	20	11100
  BCL11A-9324	-	GGCCUGUCCAAAAAGCUGCUG	21	11101
  BCL11A-9325	-	GGGCCUGUCCAAAAAGCUGCUG	22	11102
  BCL11A-9326	-	GGGGCCUGUCCAAAAAGCUGCUG	23	11103
  BCL11A-9327	-	GGGGGCCUGUCCAAAAAGCUGCUG	24	11104
  BCL11A-9328	-	GCAGCGGCACGGGAAGUG	18	11105
  BCL11A-9329	-	CGCAGCGGCACGGGAAGUG	19	11106
  BCL11A-9330	-	GCGCAGCGGCACGGGAAGUG	20	11107
  BCL11A-9331	-	GGCGCAGCGGCACGGGAAGUG	21	11108
  BCL11A-9332	-	GGGCGCAGCGGCACGGGAAGUG	22	11109
  BCL11A-9333	-	GGGGCGCAGCGGCACGGGAAGUG	23	11110
  BCL11A-9334	-	CGGGGCGCAGCGGCACGGGAAGUG	24	11111
  BCL11A-9335	-	CCCGGCACCAGCGACUUG	18	11112
  BCL11A-9336	-	ACCCGGCACCAGCGACUUG	19	11113
  BCL11A-9337	-	AACCCGGCACCAGCGACUUG	20	11114
  BCL11A-9338	-	GAACCCGGCACCAGCGACUUG	21	11115
  BCL11A-9339	-	GGAACCCGGCACCAGCGACUUG	22	11116
  BCL11A-9340	-	CGGAACCCGGCACCAGCGACUUG	23	11117
  BCL11A-9341	-	CCGGAACCCGGCACCAGCGACUUG	24	11118
  BCL11A-9342	-	CUUAAGUUCUGAGAAAAU	18	11119
  BCL11A-9343	-	CCUUAAGUUCUGAGAAAAU	19	11120
  BCL11A-9344	-	CCCUUAAGUUCUGAGAAAAU	20	11121
  BCL11A-9345	-	GCCCUUAAGUUCUGAGAAAAU	21	11122
  BCL11A-9346	-	AGCCCUUAAGUUCUGAGAAAAU	22	11123
  BCL11A-9347	-	GAGCCCUUAAGUUCUGAGAAAAU	23	11124
  BCL11A-9348	-	AGAGCCCUUAAGUUCUGAGAAAAU	24	11125
  BCL11A-9349	-	GGAUUUCUCUAGGAGACU	18	11126
  BCL11A-9350	-	UGGAUUUCUCUAGGAGACU	19	11127
  BCL11A-9351	-	AUGGAUUUCUCUAGGAGACU	20	11128
  BCL11A-9352	-	CAUGGAUUUCUCUAGGAGACU	21	11129
  BCL11A-9353	-	CCAUGGAUUUCUCUAGGAGACU	22	11130
  BCL11A-9354	-	GCCAUGGAUUUCUCUAGGAGACU	23	11131
  BCL11A-9355	-	CGCCAUGGAUUUCUCUAGGAGACU	24	11132
  BCL11A-9356	-	AUGGAUUAAGAAUCUACU	18	11133
  BCL11A-9357	-	CAUGGAUUAAGAAUCUACU	19	11134
  BCL11A-9358	-	UCAUGGAUUAAGAAUCUACU	20	11135
  BCL11A-9359	-	CUCAUGGAUUAAGAAUCUACU	21	11136
  BCL11A-9360	-	ACUCAUGGAUUAAGAAUCUACU	22	11137
  BCL11A-9361	-	CACUCAUGGAUUAAGAAUCUACU	23	11138
  BCL11A-9362	-	ACACUCAUGGAUUAAGAAUCUACU	24	11139
  BCL11A-9363	-	GCGACACUUGUGAGUACU	18	11140
  BCL11A-9364	-	AGCGACACUUGUGAGUACU	19	11141
  BCL11A-9365	-	CAGCGACACUUGUGAGUACU	20	11142
  BCL11A-9366	-	GCAGCGACACUUGUGAGUACU	21	11143
  BCL11A-9367	-	CGCAGCGACACUUGUGAGUACU	22	11144
  BCL11A-9368	-	ACGCAGCGACACUUGUGAGUACU	23	11145
  BCL11A-9369	-	GACGCAGCGACACUUGUGAGUACU	24	11146
  BCL11A-9370	-	CCACCGCAUAGAGCGCCU	18	11147
  BCL11A-9371	-	CCCACCGCAUAGAGCGCCU	19	11148
  BCL11A-6197	-	CCCCACCGCAUAGAGCGCCU	20	11149
  BCL11A-9372	-	CCCCCACCGCAUAGAGCGCCU	21	11150
  BCL11A-9373	-	ACCCCCACCGCAUAGAGCGCCU	22	11151
  BCL11A-9374	-	GACCCCCACCGCAUAGAGCGCCU	23	11152
  BCL11A-9375	-	GGACCCCCACCGCAUAGAGCGCCU	24	11153
  BCL11A-9376	-	CCCCGGGCGAGUCGGCCU	18	11154
  BCL11A-9377	-	UCCCCGGGCGAGUCGGCCU	19	11155
  BCL11A-6200	-	CUCCCCGGGCGAGUCGGCCU	20	11156
  BCL11A-9378	-	GCUCCCCGGGCGAGUCGGCCU	21	11157
  BCL11A-9379	-	UGCUCCCCGGGCGAGUCGGCCU	22	11158
  BCL11A-9380	-	CUGCUCCCCGGGCGAGUCGGCCU	23	11159
  BCL11A-9381	-	GCUGCUCCCCGGGCGAGUCGGCCU	24	11160
  BCL11A-9382	-	CCUCGUCGGAGCACUCCU	18	11161
  BCL11A-9383	-	UCCUCGUCGGAGCACUCCU	19	11162
  BCL11A-6202	-	CUCCUCGUCGGAGCACUCCU	20	11163
  BCL11A-9384	-	CCUCCUCGUCGGAGCACUCCU	21	11164
  BCL11A-9385	-	GCCUCCUCGUCGGAGCACUCCU	22	11165
  BCL11A-9386	-	UGCCUCCUCGUCGGAGCACUCCU	23	11166
  BCL11A-9387	-	UUGCCUCCUCGUCGGAGCACUCCU	24	11167
  BCL11A-9388	-	AAGAUCCCUUCCUUAGCU	18	11168
  BCL11A-9389	-	AAAGAUCCCUUCCUUAGCU	19	11169
  BCL11A-9390	-	CAAAGAUCCCUUCCUUAGCU	20	11170
  BCL11A-9391	-	UCAAAGAUCCCUUCCUUAGCU	21	11171
  BCL11A-9392	-	CUCAAAGAUCCCUUCCUUAGCU	22	11172
  BCL11A-9393	-	GCUCAAAGAUCCCUUCCUUAGCU	23	11173
  BCL11A-9394	-	AGCUCAAAGAUCCCUUCCUUAGCU	24	11174
  BCL11A-9395	-	AGAGGGUGGACUACGGCU	18	11175
  BCL11A-9396	-	GAGAGGGUGGACUACGGCU	19	11176
  BCL11A-9397	-	CGAGAGGGUGGACUACGGCU	20	11177
  BCL11A-9398	-	GCGAGAGGGUGGACUACGGCU	21	11178
  BCL11A-9399	-	AGCGAGAGGGUGGACUACGGCU	22	11179
  BCL11A-9400	-	GAGCGAGAGGGUGGACUACGGCU	23	11180
  BCL11A-9401	-	AGAGCGAGAGGGUGGACUACGGCU	24	11181
  BCL11A-9402	-	CGGUUGAAUCCAAUGGCU	18	11182
  BCL11A-9403	-	GCGGUUGAAUCCAAUGGCU	19	11183
  BCL11A-9404	-	UGCGGUUGAAUCCAAUGGCU	20	11184
  BCL11A-9405	-	CUGCGGUUGAAUCCAAUGGCU	21	11185
  BCL11A-9406	-	GCUGCGGUUGAAUCCAAUGGCU	22	11186
  BCL11A-9407	-	UGCUGCGGUUGAAUCCAAUGGCU	23	11187
  BCL11A-9408	-	GUGCUGCGGUUGAAUCCAAUGGCU	24	11188
  BCL11A-9409	-	AGCUGGACGGAGGGAUCU	18	11189
  BCL11A-9410	-	GAGCUGGACGGAGGGAUCU	19	11190
  BCL11A-6210	-	GGAGCUGGACGGAGGGAUCU	20	11191
  BCL11A-9411	-	GGGAGCUGGACGGAGGGAUCU	21	11192
  BCL11A-9412	-	GGGGAGCUGGACGGAGGGAUCU	22	11193
  BCL11A-9413	-	CGGGGAGCUGGACGGAGGGAUCU	23	11194
  BCL11A-9414	-	CCGGGGAGCUGGACGGAGGGAUCU	24	11195
  BCL11A-9415	-	CCCGCCAUGGAUUUCUCU	18	11196
  BCL11A-9416	-	UCCCGCCAUGGAUUUCUCU	19	11197
  BCL11A-6212	-	CUCCCGCCAUGGAUUUCUCU	20	11198
  BCL11A-9417	-	CCUCCCGCCAUGGAUUUCUCU	21	11199
  BCL11A-9418	-	GCCUCCCGCCAUGGAUUUCUCU	22	11200
  BCL11A-9419	-	AGCCUCCCGCCAUGGAUUUCUCU	23	11201
  BCL11A-9420	-	GAGCCUCCCGCCAUGGAUUUCUCU	24	11202
  BCL11A-9421	-	CGAGAGCCCUUAAGUUCU	18	11203
  BCL11A-9422	-	UCGAGAGCCCUUAAGUUCU	19	11204
  BCL11A-9423	-	CUCGAGAGCCCUUAAGUUCU	20	11205
  BCL11A-9424	-	GCUCGAGAGCCCUUAAGUUCU	21	11206
  BCL11A-9425	-	AGCUCGAGAGCCCUUAAGUUCU	22	11207
  BCL11A-9426	-	AAGCUCGAGAGCCCUUAAGUUCU	23	11208
  BCL11A-9427	-	GAAGCUCGAGAGCCCUUAAGUUCU	24	11209
  BCL11A-9428	-	CGCCUUUUGCCUCCUCGU	18	11210
  BCL11A-9429	-	UCGCCUUUUGCCUCCUCGU	19	11211
  BCL11A-6220	-	AUCGCCUUUUGCCUCCUCGU	20	11212
  BCL11A-9430	-	AAUCGCCUUUUGCCUCCUCGU	21	11213
  BCL11A-9431	-	CAAUCGCCUUUUGCCUCCUCGU	22	11214
  BCL11A-9432	-	ACAAUCGCCUUUUGCCUCCUCGU	23	11215
  BCL11A-9433	-	GACAAUCGCCUUUUGCCUCCUCGU	24	11216
  BCL11A-9434	-	ACGCCCCAUAUUAGUGGU	18	11217
  BCL11A-9435	-	CACGCCCCAUAUUAGUGGU	19	11218
  BCL11A-9436	-	GCACGCCCCAUAUUAGUGGU	20	11219
  BCL11A-9437	-	AGCACGCCCCAUAUUAGUGGU	21	11220
  BCL11A-9438	-	GAGCACGCCCCAUAUUAGUGGU	22	11221
  BCL11A-9439	-	GGAGCACGCCCCAUAUUAGUGGU	23	11222
  BCL11A-9440	-	GGGAGCACGCCCCAUAUUAGUGGU	24	11223
  BCL11A-9441	-	GACACUUGUGAGUACUGU	18	11224
  BCL11A-9442	-	CGACACUUGUGAGUACUGU	19	11225
  BCL11A-6230	-	GCGACACUUGUGAGUACUGU	20	11226
  BCL11A-9443	-	AGCGACACUUGUGAGUACUGU	21	11227
  BCL11A-9444	-	CAGCGACACUUGUGAGUACUGU	22	11228
  BCL11A-9445	-	GCAGCGACACUUGUGAGUACUGU	23	11229
  BCL11A-9446	-	CGCAGCGACACUUGUGAGUACUGU	24	11230
  BCL11A-9447	-	CGCGGGUUGGUAUCCCUU	18	11231
  BCL11A-9448	-	CCGCGGGUUGGUAUCCCUU	19	11232
  BCL11A-9449	-	CCCGCGGGUUGGUAUCCCUU	20	11233
  BCL11A-9450	-	CCCCGCGGGUUGGUAUCCCUU	21	11234
  BCL11A-9451	-	ACCCCGCGGGUUGGUAUCCCUU	22	11235
  BCL11A-9452	-	GACCCCGCGGGUUGGUAUCCCUU	23	11236
  BCL11A-9453	-	UGACCCCGCGGGUUGGUAUCCCUU	24	11237
  BCL11A-9454	-	AGAUCCCUUCCUUAGCUU	18	11238
  BCL11A-9455	-	AAGAUCCCUUCCUUAGCUU	19	11239
  BCL11A-6234	-	AAAGAUCCCUUCCUUAGCUU	20	11240
  BCL11A-9456	-	CAAAGAUCCCUUCCUUAGCUU	21	11241
  BCL11A-9457	-	UCAAAGAUCCCUUCCUUAGCUU	22	11242
  BCL11A-9458	-	CUCAAAGAUCCCUUCCUUAGCUU	23	11243
  BCL11A-9459	-	GCUCAAAGAUCCCUUCCUUAGCUU	24	11244
  BCL11A-9460	-	CUCGAGAGCCCUUAAGUU	18	11245
  BCL11A-9461	-	GCUCGAGAGCCCUUAAGUU	19	11246
  BCL11A-9462	-	AGCUCGAGAGCCCUUAAGUU	20	11247
  BCL11A-9463	-	AAGCUCGAGAGCCCUUAAGUU	21	11248
  BCL11A-9464	-	GAAGCUCGAGAGCCCUUAAGUU	22	11249
  BCL11A-9465	-	GGAAGCUCGAGAGCCCUUAAGUU	23	11250
  BCL11A-9466	-	UGGAAGCUCGAGAGCCCUUAAGUU	24	11251
  BCL11A-9467	-	GGCAAGACGUUCAAAUUU	18	11252
  BCL11A-9468	-	CGGCAAGACGUUCAAAUUU	19	11253
  BCL11A-9469	-	GCGGCAAGACGUUCAAAUUU	20	11254
  BCL11A-9470	-	UGCGGCAAGACGUUCAAAUUU	21	11255
  BCL11A-9471	-	CUGCGGCAAGACGUUCAAAUUU	22	11256
  BCL11A-9472	-	UCUGCGGCAAGACGUUCAAAUUU	23	11257
  BCL11A-9473	-	UUCUGCGGCAAGACGUUCAAAUUU	24	11258

• Table 17A 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 17A
  1st Tier

  			Target	SEQ
  	DNA		Site	ID
  gRNA Name	Strand	Targeting Domain	Length	NO:
  BCL11A-9474	+	CGAUUGGUGAAGGGGAA	17	11259
  BCL11A-9475	+	AUUGGAUGCUUUUUUCA	17	11260
  BCL11A-9476	−	CAGGUCACGCCAGAGGA	17	11261
  BCL11A-9477	+	CUUACGCGAGAAUUCCC	17	11262
  BCL11A-9478	+	CCUGGAUGCCAACCUCC	17	11263
  BCL11A-9479	−	AACAAUGCAAUGGCAGC	17	11264
  BCL11A-9480	+	GGGGAAGGUGGCUUAUC	17	11265
  BCL11A-9481	+	GGUUCAUCAUCUGUAAG	17	11266
  BCL11A-5334	+	UGCACUCAUCCCAGGCG	17	11267
  BCL11A-9482	+	UUAAGUGCUGGGGUUUG	17	11268
  BCL11A-9483	+	CCAACCUCCACGGGAUU	17	11269
  BCL11A-9484	+	UCUCGAUUGGUGAAGGGGAA	20	11270
  BCL11A-9485	+	GGGAUUGGAUGCUUUUUUCA	20	11271
  BCL11A-9486	−	AUCCAGGUCACGCCAGAGGA	20	11272
  BCL11A-9487	+	UUACUUACGCGAGAAUUCCC	20	11273
  BCL11A-6420	+	UGACCUGGAUGCCAACCUCC	20	11274
  BCL11A-9488	−	GGAAACAAUGCAAUGGCAGC	20	11275
  BCL11A-9489	+	GAAGGGGAAGGUGGCUUAUC	20	11276
  BCL11A-9490	+	UCUGGUUCAUCAUCUGUAAG	20	11277
  BCL11A-5480	+	UUCUGCACUCAUCCCAGGCG	20	11278
  BCL11A-9491	+	UGCUUAAGUGCUGGGGUUUG	20	11279
  BCL11A-9492	+	AUGCCAACCUCCACGGGAUU	20	11280

• Table 17B 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 500 bp 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 17B
  3rd Tier

  			Target	SEQ
  	DNA		Site	ID
  gRNA Name	Strand	Targeting Domain	Length	NO:
  BCL11A-5515	+	UCCGACGAGGAGGCAAA	17	11281
  BCL11A-5520	−	CUUCCGGCCUGGCAGAA	17	11282
  BCL11A-9493	+	UCCGUGUUCGCUUUCUA	17	11283
  BCL11A-9494	−	AGAGCGAGAGGGUGGAC	17	11284
  BCL11A-9495	+	CGGGAGGCUCCAUAGCC	17	11285
  BCL11A-9496	−	UUCCCAGCCACCUCUCC	17	11286
  BCL11A-9497	+	AGCUGGGGCUGCCCAGC	17	11287
  BCL11A-9498	−	GCUAUGGAGCCUCCCGC	17	11288
  BCL11A-9499	+	CGGCCAGGUGGCCGCGC	17	11289
  BCL11A-9500	+	GCGUCUUCAUGUGGCGC	17	11290
  BCL11A-9501	+	UCAGAACUUAAGGGCUC	17	11291
  BCL11A-9502	−	AGCUCAAAGAUCCCUUC	17	11292
  BCL11A-9503	+	GCAGGUCGAACUCCUUC	17	11293
  BCL11A-9504	+	GGGGCGUCGCCAGGAAG	17	11294
  BCL11A-9505	−	CCAGGAUCAGUAUCGAG	17	11295
  BCL11A-9506	+	GGCUGGGAGGGAGGAGG	17	11296
  BCL11A-9507	+	GACUUGACCGUCAUGGG	17	11297
  BCL11A-9508	+	CGGCCUCGGCCAGGUGG	17	11298
  BCL11A-5799	+	GCAUGUGCGUCUUCAUG	17	11299
  BCL11A-9509	+	CGCACAGGUUGCACUUG	17	11300
  BCL11A-9510	+	ACUCCUUCUCGAGCUUG	17	11301
  BCL11A-9511	−	AACACGCACAGAACACU	17	11302
  BCL11A-9512	−	CCUCGGAGAACGGGAGU	17	11303
  BCL11A-9513	+	GGUCAGGGGACUUCCGU	17	11304
  BCL11A-5874	+	UGCUCCGACGAGGAGGCAAA	20	11305
  BCL11A-5879	−	AGGCUUCCGGCCUGGCAGAA	20	11306
  BCL11A-9514	+	ACUUCCGUGUUCGCUUUCUA	20	11307
  BCL11A-9515	−	CGGAGAGCGAGAGGGUGGAC	20	11308
  BCL11A-9516	+	UGGCGGGAGGCUCCAUAGCC	20	11309
  BCL11A-8754	−	UCCUUCCCAGCCACCUCUCC	20	11310
  BCL11A-9517	+	GCGAGCUGGGGCUGCCCAGC	20	11311
  BCL11A-9518	−	AUGGCUAUGGAGCCUCCCGC	20	11312
  BCL11A-9519	+	CCUCGGCCAGGUGGCCGCGC	20	11313
  BCL11A-9520	+	UGUGCGUCUUCAUGUGGCGC	20	11314
  BCL11A-7725	+	UUCUCAGAACUUAAGGGCUC	20	11315
  BCL11A-9521	−	GGCAGCUCAAAGAUCCCUUC	20	11316
  BCL11A-7752	+	GGGGCAGGUCGAACUCCUUC	20	11317
  BCL11A-9522	+	GGGGGGGCGUCGCCAGGAAG	20	11318
  BCL11A-9523	−	AUACCAGGAUCAGUAUCGAG	20	11319
  BCL11A-9524	+	GGGGGCUGGGAGGGAGGAGG	20	11320
  BCL11A-9525	+	UCGGACUUGACCGUCAUGGG	20	11321
  BCL11A-9526	+	CCUCGGCCUCGGCCAGGUGG	20	11322
  BCL11A-6165	+	UGUGCAUGUGCGUCUUCAUG	20	11323
  BCL11A-8204	+	GGUCGCACAGGUUGCACUUG	20	11324
  BCL11A-9527	+	CGAACUCCUUCUCGAGCUUG	20	11325
  BCL11A-9528	−	UGCAACACGCACAGAACACU	20	11326
  BCL11A-9529	−	ACUCCUCGGAGAACGGGAGU	20	11327
  BCL11A-9530	+	CGGGGUCAGGGGACUUCCGU	20	11328

• Table 18A provides exemplary targeting domains for knocking down the BCL11A 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 BCL11A gene (e.g., reduce or eliminate BCL11A gene expression, BCL11A protein function, or the level of BCL11A protein). One or more gRNA may be used to target an eiCas9 to the promoter region of the BCL11A gene.

• TABLE 18A
  1st Tier

  			Target	SEQ
  	DNA		Site	ID
  gRNA Name	Strand	Targeting Domain	Length	NO:
  BCL11A-9531	+	AAGUGCAUACACGGCAA	17	11329
  BCL11A-5319	+	UUGCUUGCGGCGAGACA	17	11330
  BCL11A-5320	−	AUGUCUCGCCGCAAGCA	17	11331
  BCL11A-9532	−	UGACGUUCAAGUUCGCA	17	11332
  BCL11A-9533	+	UUGUGGGAGAGCCGUCA	17	11333
  BCL11A-9534	+	ACGGCAAUGGUUCCAGA	17	11334
  BCL11A-9535	−	GCGCUCGCUGCGGCCAC	17	11335
  BCL11A-4560	+	ACGCCAGACGCGGCCCC	17	11336
  BCL11A-9536	+	UUCACAUCGGGAGAGCC	17	11337
  BCL11A-9537	+	GUUCACAUCGGGAGAGC	17	11338
  BCL11A-9538	−	UAAUCACGAGAGCGCGC	17	11339
  BCL11A-9539	−	CUGACGUUCAAGUUCGC	17	11340
  BCL11A-5327	+	CCCGUUUGCUUAAGUGC	17	11341
  BCL11A-9540	+	ACGGCUCGGUUCACAUC	17	11342
  BCL11A-9541	+	CUUGAACGUCAGGAGUC	17	11343
  BCL11A-9542	+	CUGCGAACUUGAACGUC	17	11344
  BCL11A-9543	−	CCCCCGGGGGCCGCGUC	17	11345
  BCL11A-9544	+	UCCGCGGACGCCAGACG	17	11346
  BCL11A-9545	−	GACUAGAAGCAAAAGCG	17	11347
  BCL11A-5335	+	AGACAUGGUGGGCUGCG	17	11348
  BCL11A-9546	−	AAAACCUCCGAGAGUCG	17	11349
  BCL11A-9547	+	UUUACCUCGACUCUCGG	17	11350
  BCL11A-9548	−	AGUCCGCGUGUGUGGGG	17	11351
  BCL11A-5336	+	CGUUUGCUUAAGUGCUG	17	11352
  BCL11A-9549	−	UAGAGUCCGCGUGUGUG	17	11353
  BCL11A-9550	+	GACGGCUCGGUUCACAU	17	11354
  BCL11A-9551	−	CUCCCCGCACUGGCCAU	17	11355
  BCL11A-9552	+	CGGCAAUGGUUCCAGAU	17	11356
  BCL11A-9553	+	GCGGGCGGACGACGGCU	17	11357
  BCL11A-5338	+	CCGUUUGCUUAAGUGCU	17	11358
  BCL11A-5340	+	UUGCGGCGAGACAUGGU	17	11359
  BCL11A-9554	+	CGUGGCCGGGAGAGAAGAAA	20	11360
  BCL11A-5345	+	GCCUUGCUUGCGGCGAGACA	20	11361
  BCL11A-5346	−	ACCAUGUCUCGCCGCAAGCA	20	11362
  BCL11A-9555	−	UCCUGACGUUCAAGUUCGCA	20	11363
  BCL11A-9556	+	ACACCAAUGGACACACAUCA	20	11364
  BCL11A-9557	+	UACACGGCAAUGGUUCCAGA	20	11365
  BCL11A-9558	+	GCCAAUGGCCAGUGCGGGGA	20	11366
  BCL11A-9559	+	AAUGGUUCCAGAUGGGAUGA	20	11367
  BCL11A-9560	−	GAGUCUCCUUCUUUCUAACC	20	11368
  BCL11A-9561	+	CGGUUCACAUCGGGAGAGCC	20	11369
  BCL11A-9562	+	UCGGUUCACAUCGGGAGAGC	20	11370
  BCL11A-9563	−	CCGCGUGUGUGGGGGGGAGC	20	11371
  BCL11A-9564	−	UAAUAAUCACGAGAGCGCGC	20	11372
  BCL11A-9565	+	AAAUAAUACAAAGAUGGCGC	20	11373
  BCL11A-9566	−	CUCCUGACGUUCAAGUUCGC	20	11374
  BCL11A-9567	+	GAGACACACAAAACAUGGGC	20	11375
  BCL11A-5352	+	AUUCCCGUUUGCUUAAGUGC	20	11376
  BCL11A-9568	+	ACGACGGCUCGGUUCACAUC	20	11377
  BCL11A-9569	−	CGCACUUGAACUUGCAGCUC	20	11378
  BCL11A-9570	+	UCCCUGCGAACUUGAACGUC	20	11379
  BCL11A-9571	−	UCGAGGUAAAAGAGAUAAAG	20	11380
  BCL11A-9572	+	CCAAUGGCCAGUGCGGGGAG	20	11381
  BCL11A-4351	+	GACGCCAGACGCGGCCCCCG	20	11382
  BCL11A-9573	−	UGCGGCCACUGGUGAGCCCG	20	11383
  BCL11A-9574	−	GGGGCCGCGUCUGGCGUCCG	20	11384
  BCL11A-5359	+	GCGAGACAUGGUGGGCUGCG	20	11385
  BCL11A-9575	−	AGAAAAACCUCCGAGAGUCG	20	11386
  BCL11A-4561	+	ACGCCAGACGCGGCCCCCGG	20	11387
  BCL11A-9576	+	UCUUUUACCUCGACUCUCGG	20	11388
  BCL11A-9577	−	UAGAGUCCGCGUGUGUGGGG	20	11389
  BCL11A-9578	−	UUUAGAGUCCGCGUGUGUGG	20	11390
  BCL11A-9579	+	CAAUGGUUCCAGAUGGGAUG	20	11391
  BCL11A-5361	+	CGGCGAGACAUGGUGGGCUG	20	11392
  BCL11A-9580	+	CUGAGCUGCAAGUUCAAGUG	20	11393
  BCL11A-9581	−	CAUUUUAGAGUCCGCGUGUG	20	11394
  BCL11A-9582	+	GACGACGGCUCGGUUCACAU	20	11395
  BCL11A-9583	−	AGCCCCUGAUGUGUGUCCAU	20	11396
  BCL11A-9584	+	GCGGCGGGCGGACGACGGCU	20	11397
  BCL11A-9585	+	AUCUCUUUUACCUCGACUCU	20	11398
  BCL11A-5365	+	UGCUUGCGGCGAGACAUGGU	20	11399
  BCL11A-9586	−	AUUUUAGAGUCCGCGUGUGU	20	11400

• Table 18B provides exemplary targeting domains for knocking down the BCL11A 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 BCL11A gene (e.g., reduce or eliminate BCL11A gene expression, BCL11A protein function, or the level of BCL11A protein). One or more gRNA may be used to target an eiCas9 to the promoter region of the BCL11A gene.

• TABLE 18B
  2nd Tier

  	DNA		Target Site	SEQ ID
  gRNA Name	Strand	Targeting Domain	Length	NO:
  BCL11A-9587	+	GAGAGAGAUGAAAAAAA	17	11401
  BCL11A-5369	-	CCCAGCACUUAAGCAAA	17	11402
  BCL11A-9588	-	UUAUUUUGGAUGUCAAA	17	11403
  BCL11A-4473	+	GGCCGGGAGAGAAGAAA	17	11404
  BCL11A-9589	+	GCAGGGGUGGGAGGAAA	17	11405
  BCL11A-9590	-	GAGGUAAAAGAGAUAAA	17	11406
  BCL11A-9591	+	AAUUAAAUAAAAUUAAA	17	11407
  BCL11A-9592	+	GGGGAAGCUCACACCAA	17	11408
  BCL11A-4574	+	AGACCAGGACAAGCCAA	17	11409
  BCL11A-9593	+	UGGCCGGGAGAGAAGAA	17	11410
  BCL11A-4491	+	GGGCGAGCAGGAGAGAA	17	11411
  BCL11A-9594	+	GGCAGGGGUGGGAGGAA	17	11412
  BCL11A-4570	+	AGAAGGGGAGGAGGGAA	17	11413
  BCL11A-9595	-	CGAGGUAAAAGAGAUAA	17	11414
  BCL11A-4625	+	CAGAGACACACAAAACA	17	11415
  BCL11A-9596	+	UCUCAAAAGUGCAUACA	17	11416
  BCL11A-9597	-	GUGUGUGGGGGGGAGCA	17	11417
  BCL11A-9598	+	AAUACAAAGAUGGCGCA	17	11418
  BCL11A-9599	+	CACACAAAACAUGGGCA	17	11419
  BCL11A-9600	+	AGAAGAAAGGGGUGGCA	17	11420
  BCL11A-9601	+	CCAAUGGACACACAUCA	17	11421
  BCL11A-9602	-	CUUGAACUUGCAGCUCA	17	11422
  BCL11A-4529	+	AAAAAAAAAAAAAAAGA	17	11423
  BCL11A-9603	+	UAGAAAUAAUACAAAGA	17	11424
  BCL11A-9604	+	GAGCCGGGUUAGAAAGA	17	11425
  BCL11A-4592	+	AGGGCGAGCAGGAGAGA	17	11426
  BCL11A-4534	-	AAAGCGAGGGGGAGAGA	17	11427
  BCL11A-9605	+	GAGAGAAGAGAGAUAGA	17	11428
  BCL11A-4674	+	CGGCGGCGGGCGGACGA	17	11429
  BCL11A-4494	+	GGGGAGGGGCGGGCCGA	17	11430
  BCL11A-9606	-	ACUAGAAGCAAAAGCGA	17	11431
  BCL11A-4591	+	AGGAGAGAAGGGGAGGA	17	11432
  BCL11A-4399	+	GAGAAGGGGAGGAGGGA	17	11433
  BCL11A-4499	+	GGGGCGGGCCGAGGGGA	17	11434
  BCL11A-9607	+	AAUGGCCAGUGCGGGGA	17	11435
  BCL11A-4562	+	ACGCGGCCCCCGGGGGA	17	11436
  BCL11A-9608	+	AACGUCAGGAGUCUGGA	17	11437
  BCL11A-9609	-	UUAAAAAAAAGCCAUGA	17	11438
  BCL11A-9610	+	GGUUCCAGAUGGGAUGA	17	11439
  BCL11A-5383	-	CCAGCACUUAAGCAAAC	17	11440
  BCL11A-9611	-	CCUCCCCCUCCCCGCAC	17	11441
  BCL11A-9612	-	UCUCCUUCUUUCUAACC	17	11442
  BCL11A-9613	+	GACAUGAAAAAGAGACC	17	11443
  BCL11A-4662	+	CGCCAGACGCGGCCCCC	17	11444
  BCL11A-9614	-	CGGCCCGCCCCUCCCCC	17	11445
  BCL11A-9615	-	UCGGCCCGCCCCUCCCC	17	11446
  BCL11A-9616	+	GCGGCGGUGGCGUGGCC	17	11447
  BCL11A-9617	-	ACCCCUUUCUUCUCUCC	17	11448
  BCL11A-9618	-	UGGCCAUUGGCUUGUCC	17	11449
  BCL11A-9619	+	ACAUGGGCAGGGCGAGC	17	11450
  BCL11A-9620	-	CGUGUGUGGGGGGGAGC	17	11451
  BCL11A-9621	+	GGGGGCGCUGGGGCCGC	17	11452
  BCL11A-4646	+	CCGAGGGGAGGGGGCGC	17	11453
  BCL11A-9622	+	UAAUACAAAGAUGGCGC	17	11454
  BCL11A-4441	+	GCGGCGGCGGCGGCGGC	17	11455
  BCL11A-9623	+	GGACACACAUCAGGGGC	17	11456
  BCL11A-4429	+	GCCCCCGGGGGAGGGGC	17	11457
  BCL11A-5392	+	AUGGUGGGCUGCGGGGC	17	11458
  BCL11A-9624	+	AGGGGGAGGUGCGGGGC	17	11459
  BCL11A-9625	+	ACACACAAAACAUGGGC	17	11460
  BCL11A-9626	+	CGCGGCGGUGGCGUGGC	17	11461
  BCL11A-9627	+	GAGAAGAAAGGGGUGGC	17	11462
  BCL11A-5395	+	GAGACAUGGUGGGCUGC	17	11463
  BCL11A-9628	+	AAGCCAAUGGCCAGUGC	17	11464
  BCL11A-9629	+	CGGGGAGGGGGAGGUGC	17	11465
  BCL11A-9630	+	ACCAAUGGACACACAUC	17	11466
  BCL11A-9631	-	AAAACCCUCAUCCCAUC	17	11467
  BCL11A-9632	-	ACUUGAACUUGCAGCUC	17	11468
  BCL11A-9633	-	GAUGAAGAUAUUUUCUC	17	11469
  BCL11A-4528	+	AAAAAAAAAAAAAAAAG	17	11470
  BCL11A-4433	+	GCCGGGAGAGAAGAAAG	17	11471
  BCL11A-9634	-	AGGUAAAAGAGAUAAAG	17	11472
  BCL11A-4475	+	GGCGAGCAGGAGAGAAG	17	11473
  BCL11A-4389	+	GAAGGGGAGGAGGGAAG	17	11474
  BCL11A-9635	+	GGCCGCGGGCUCACCAG	17	11475
  BCL11A-9636	+	GAAGAAAGGGGUGGCAG	17	11476
  BCL11A-9637	+	CAAUGGACACACAUCAG	17	11477
  BCL11A-9638	-	UUGAACUUGCAGCUCAG	17	11478
  BCL11A-4543	-	AAGCGAGGGGGAGAGAG	17	11479
  BCL11A-4533	-	AAAAGCGAGGGGGAGAG	17	11480
  BCL11A-4485	+	GGGAGGGGCGGGCCGAG	17	11481
  BCL11A-9639	-	CUAGAAGCAAAAGCGAG	17	11482
  BCL11A-4492	+	GGGCGGGCCGAGGGGAG	17	11483
  BCL11A-9640	+	AUGGCCAGUGCGGGGAG	17	11484
  BCL11A-4665	+	CGCGGCCCCCGGGGGAG	17	11485
  BCL11A-9641	+	AGAGAGAAGAGAGAUAG	17	11486
  BCL11A-9642	+	GCUCCCCCCCACACACG	17	11487
  BCL11A-4427	+	GCCAGACGCGGCCCCCG	17	11488
  BCL11A-9643	-	GGCCCGCCCCUCCCCCG	17	11489
  BCL11A-9644	-	GGCCACUGGUGAGCCCG	17	11490
  BCL11A-4670	-	CGGCCACGCCACCGCCG	17	11491
  BCL11A-4470	+	GGCCGCAGCGAGCGCCG	17	11492
  BCL11A-4502	+	GGGGGAGGGGCGGGCCG	17	11493
  BCL11A-9645	+	AGGGGGCGCUGGGGCCG	17	11494
  BCL11A-9646	+	CGGGGCGGGGGGCUCCG	17	11495
  BCL11A-9647	-	GCCGCGUCUGGCGUCCG	17	11496
  BCL11A-9648	+	GGGGGAGGUGCGGGGCG	17	11497
  BCL11A-9649	+	GCGCCGCGGCGGUGGCG	17	11498
  BCL11A-9650	+	AGCCAAUGGCCAGUGCG	17	11499
  BCL11A-9651	+	GGGGAGGGGGAGGUGCG	17	11500
  BCL11A-9652	-	GGUAAAAGAGAUAAAGG	17	11501
  BCL11A-9653	-	UGAACUUGCAGCUCAGG	17	11502
  BCL11A-9654	-	UAGAAGCAAAAGCGAGG	17	11503
  BCL11A-4627	+	CAGGAGAGAAGGGGAGG	17	11504
  BCL11A-4480	+	GGCGGGCCGAGGGGAGG	17	11505
  BCL11A-9655	+	UGGCCAGUGCGGGGAGG	17	11506
  BCL11A-4634	+	CCAGACGCGGCCCCCGG	17	11507
  BCL11A-9656	-	GCCCGCCCCUCCCCCGG	17	11508
  BCL11A-4660	+	CGCAGCGAGCGCCGCGG	17	11509
  BCL11A-4588	+	AGCGAGCGCCGCGGCGG	17	11510
  BCL11A-4478	+	GGCGGCGGCGGCGGCGG	17	11511
  BCL11A-4447	+	GCGGGCGGCGGCGGCGG	17	11512
  BCL11A-4500	+	GGGGCGGGCGGCGGCGG	17	11513
  BCL11A-5409	+	UGCGGGGCGGGCGGCGG	17	11514
  BCL11A-5410	+	GGCUGCGGGGCGGGCGG	17	11515
  BCL11A-9657	+	GGGGAGGUGCGGGGCGG	17	11516
  BCL11A-9658	+	GGGGUGGGAGGAAAGGG	17	11517
  BCL11A-9659	-	GAACUUGCAGCUCAGGG	17	11518
  BCL11A-4444	+	GCGGCGGCGGCGGCGGG	17	11519
  BCL11A-5411	+	GUGGGCUGCGGGGCGGG	17	11520
  BCL11A-9660	+	GGGAGGUGCGGGGCGGG	17	11521
  BCL11A-4483	+	GGGAGAGAAGAAAGGGG	17	11522
  BCL11A-4407	+	GAGCAGGAGAGAAGGGG	17	11523
  BCL11A-9661	+	GAAAGGGGUGGCAGGGG	17	11524
  BCL11A-4593	+	AGGGGCGGGCCGAGGGG	17	11525
  BCL11A-4467	+	GGCCCCCGGGGGAGGGG	17	11526
  BCL11A-5413	+	CAUGGUGGGCUGCGGGG	17	11527
  BCL11A-9662	+	CAAUGGCCAGUGCGGGG	17	11528
  BCL11A-9663	+	GAGGGGGAGGUGCGGGG	17	11529
  BCL11A-9664	+	CCAGUGCGGGGAGGGGG	17	11530
  BCL11A-4395	+	GACGCGGCCCCCGGGGG	17	11531
  BCL11A-9665	+	GGGAGGAAAGGGUGGGG	17	11532
  BCL11A-9666	+	UGGGAGGAAAGGGUGGG	17	11533
  BCL11A-9667	+	GGGGUGGCAGGGGUGGG	17	11534
  BCL11A-9668	-	GAGUCCGCGUGUGUGGG	17	11535
  BCL11A-5414	+	CUUGCGGCGAGACAUGG	17	11536
  BCL11A-9669	+	GUGGGAGGAAAGGGUGG	17	11537
  BCL11A-9670	-	AGAGUCCGCGUGUGUGG	17	11538
  BCL11A-9671	+	UGGUUCCAGAUGGGAUG	17	11539
  BCL11A-9672	+	GAGGGGAGGGGGCGCUG	17	11540
  BCL11A-9673	-	CGCCGCGGCGCUCGCUG	17	11541
  BCL11A-5422	+	CGAGACAUGGUGGGCUG	17	11542
  BCL11A-9674	+	AGCUGCAAGUUCAAGUG	17	11543
  BCL11A-9675	+	CAAGCCAAUGGCCAGUG	17	11544
  BCL11A-9676	+	GCGGGGAGGGGGAGGUG	17	11545
  BCL11A-9677	+	GGUGGGAGGAAAGGGUG	17	11546
  BCL11A-9678	-	UUUAGAGUCCGCGUGUG	17	11547
  BCL11A-9679	+	GCAGGGAAGAUGAAUUG	17	11548
  BCL11A-5426	+	GGGGUUUGCCUUGCUUG	17	11549
  BCL11A-9680	+	AGAGACACACAAAACAU	17	11550
  BCL11A-9681	-	CCCUGAUGUGUGUCCAU	17	11551
  BCL11A-5431	+	AUUAUUAUUACUAUUAU	17	11552
  BCL11A-9682	-	CCAGCGCCCCCUCCCCU	17	11553
  BCL11A-9683	+	CGAGGGGAGGGGGCGCU	17	11554
  BCL11A-9684	+	UCUUUUACCUCGACUCU	17	11555
  BCL11A-9685	+	GGGUGGGAGGAAAGGGU	17	11556
  BCL11A-9686	+	AAAGGGGUGGCAGGGGU	17	11557
  BCL11A-9687	-	UUAGAGUCCGCGUGUGU	17	11558
  BCL11A-9688	+	CAGGGAAGAUGAAUUGU	17	11559
  BCL11A-5439	+	UUAUUAUUACUAUUAUU	17	11560
  BCL11A-9689	-	UUAUUUCUAAUUUAUUU	17	11561
  BCL11A-9690	+	AGAGAGAGAGAUGAAAAAAA	20	11562
  BCL11A-5443	-	AACCCCAGCACUUAAGCAAA	20	11563
  BCL11A-9691	-	AAUUUAUUUUGGAUGUCAAA	20	11564
  BCL11A-9692	+	GUGGCAGGGGUGGGAGGAAA	20	11565
  BCL11A-9693	-	GUCGAGGUAAAAGAGAUAAA	20	11566
  BCL11A-9694	+	UAAAAUUAAAUAAAAUUAAA	20	11567
  BCL11A-9695	+	GAAGGGGAAGCUCACACCAA	20	11568
  BCL11A-4541	+	AAGAGACCAGGACAAGCCAA	20	11569
  BCL11A-9696	+	CAAAAGUGCAUACACGGCAA	20	11570
  BCL11A-9697	+	GCGUGGCCGGGAGAGAAGAA	20	11571
  BCL11A-4422	+	GCAGGGCGAGCAGGAGAGAA	20	11572
  BCL11A-9698	+	GGUGGCAGGGGUGGGAGGAA	20	11573
  BCL11A-4404	+	GAGAGAAGGGGAGGAGGGAA	20	11574
  BCL11A-9699	-	AGUCGAGGUAAAAGAGAUAA	20	11575
  BCL11A-4455	+	GGACAGAGACACACAAAACA	20	11576
  BCL11A-9700	+	CUGUCUCAAAAGUGCAUACA	20	11577
  BCL11A-9701	-	CGCGUGUGUGGGGGGGAGCA	20	11578
  BCL11A-9702	+	AAUAAUACAAAGAUGGCGCA	20	11579
  BCL11A-9703	+	AGACACACAAAACAUGGGCA	20	11580
  BCL11A-9704	+	GAGAGAAGAAAGGGGUGGCA	20	11581
  BCL11A-9705	-	GCACUUGAACUUGCAGCUCA	20	11582
  BCL11A-9706	+	GAAUUGUGGGAGAGCCGUCA	20	11583
  BCL11A-4527	+	AAAAAAAAAAAAAAAAAAGA	20	11584
  BCL11A-9707	+	AAUUAGAAAUAAUACAAAGA	20	11585
  BCL11A-9708	+	GGAGAGCCGGGUUAGAAAGA	20	11586
  BCL11A-4464	+	GGCAGGGCGAGCAGGAGAGA	20	11587
  BCL11A-4418	-	GCAAAAGCGAGGGGGAGAGA	20	11588
  BCL11A-9709	+	AGAGAGAGAAGAGAGAUAGA	20	11589
  BCL11A-4673	+	CGGCGGCGGCGGGCGGACGA	20	11590
  BCL11A-4648	+	CCGGGGGAGGGGCGGGCCGA	20	11591
  BCL11A-9710	-	AGGACUAGAAGCAAAAGCGA	20	11592
  BCL11A-4584	+	AGCAGGAGAGAAGGGGAGGA	20	11593
  BCL11A-4459	+	GGAGAGAAGGGGAGGAGGGA	20	11594
  BCL11A-4461	+	GGAGGGGCGGGCCGAGGGGA	20	11595
  BCL11A-4624	+	CAGACGCGGCCCCCGGGGGA	20	11596
  BCL11A-9711	+	UUGAACGUCAGGAGUCUGGA	20	11597
  BCL11A-9712	-	UGCUUAAAAAAAAGCCAUGA	20	11598
  BCL11A-5458	-	ACCCCAGCACUUAAGCAAAC	20	11599
  BCL11A-9713	-	GCGGCGCUCGCUGCGGCCAC	20	11600
  BCL11A-9714	-	GCACCUCCCCCUCCCCGCAC	20	11601
  BCL11A-9715	+	CUGGACAUGAAAAAGAGACC	20	11602
  BCL11A-4456	+	GGACGCCAGACGCGGCCCCC	20	11603
  BCL11A-9716	-	CCUCGGCCCGCCCCUCCCCC	20	11604
  BCL11A-4362	+	CGGACGCCAGACGCGGCCCC	20	11605
  BCL11A-9717	-	CCCUCGGCCCGCCCCUCCCC	20	11606
  BCL11A-9718	+	GCCGCGGCGGUGGCGUGGCC	20	11607
  BCL11A-9719	-	GCCACCCCUUUCUUCUCUCC	20	11608
  BCL11A-9720	-	CACUGGCCAUUGGCUUGUCC	20	11609
  BCL11A-9721	+	AAAACAUGGGCAGGGCGAGC	20	11610
  BCL11A-9722	+	GGAGGGGGCGCUGGGGCCGC	20	11611
  BCL11A-4490	+	GGGCCGAGGGGAGGGGGCGC	20	11612
  BCL11A-4442	+	GCGGCGGCGGCGGCGGCGGC	20	11613
  BCL11A-9723	+	AAUGGACACACAUCAGGGGC	20	11614
  BCL11A-4439	+	GCGGCCCCCGGGGGAGGGGC	20	11615
  BCL11A-5465	+	GACAUGGUGGGCUGCGGGGC	20	11616
  BCL11A-9724	+	GGGAGGGGGAGGUGCGGGGC	20	11617
  BCL11A-9725	+	CGCCGCGGCGGUGGCGUGGC	20	11618
  BCL11A-9726	+	GGAGAGAAGAAAGGGGUGGC	20	11619
  BCL11A-5468	+	GGCGAGACAUGGUGGGCUGC	20	11620
  BCL11A-9727	+	GACAAGCCAAUGGCCAGUGC	20	11621
  BCL11A-9728	+	GUGCGGGGAGGGGGAGGUGC	20	11622
  BCL11A-9729	+	CACACCAAUGGACACACAUC	20	11623
  BCL11A-9730	-	GAAAAAACCCUCAUCCCAUC	20	11624
  BCL11A-9731	-	ACUGAUGAAGAUAUUUUCUC	20	11625
  BCL11A-9732	+	GAACUUGAACGUCAGGAGUC	20	11626
  BCL11A-9733	-	CCUCCCCCGGGGGCCGCGUC	20	11627
  BCL11A-4526	+	AAAAAAAAAAAAAAAAAAAG	20	11628
  BCL11A-9734	+	GUGGCCGGGAGAGAAGAAAG	20	11629
  BCL11A-4629	+	CAGGGCGAGCAGGAGAGAAG	20	11630
  BCL11A-4577	+	AGAGAAGGGGAGGAGGGAAG	20	11631
  BCL11A-9735	+	UGGGGCCGCGGGCUCACCAG	20	11632
  BCL11A-9736	+	AGAGAAGAAAGGGGUGGCAG	20	11633
  BCL11A-9737	+	CACCAAUGGACACACAUCAG	20	11634
  BCL11A-9738	-	CACUUGAACUUGCAGCUCAG	20	11635
  BCL11A-4611	-	CAAAAGCGAGGGGGAGAGAG	20	11636
  BCL11A-4583	-	AGCAAAAGCGAGGGGGAGAG	20	11637
  BCL11A-4677	+	CGGGGGAGGGGCGGGCCGAG	20	11638
  BCL11A-9739	-	GGACUAGAAGCAAAAGCGAG	20	11639
  BCL11A-4411	+	GAGGGGCGGGCCGAGGGGAG	20	11640
  BCL11A-4575	+	AGACGCGGCCCCCGGGGGAG	20	11641
  BCL11A-9740	+	GAGAGAGAGAAGAGAGAUAG	20	11642
  BCL11A-9741	+	CCUGCUCCCCCCCACACACG	20	11643
  BCL11A-9742	+	GGCUCCGCGGACGCCAGACG	20	11644
  BCL11A-9743	-	CUCGGCCCGCCCCUCCCCCG	20	11645
  BCL11A-9744	-	UCCCGGCCACGCCACCGCCG	20	11646
  BCL11A-9745	+	AGUGGCCGCAGCGAGCGCCG	20	11647
  BCL11A-4642	+	CCCGGGGGAGGGGCGGGCCG	20	11648
  BCL11A-9746	+	GGGAGGGGGCGCUGGGGCCG	20	11649
  BCL11A-9747	+	GUGCGGGGCGGGGGGCUCCG	20	11650
  BCL11A-9748	-	CAGGACUAGAAGCAAAAGCG	20	11651
  BCL11A-9749	+	GGAGGGGGAGGUGCGGGGCG	20	11652
  BCL11A-9750	+	CGAGCGCCGCGGCGGUGGCG	20	11653
  BCL11A-9751	+	ACAAGCCAAUGGCCAGUGCG	20	11654
  BCL11A-9752	+	UGCGGGGAGGGGGAGGUGCG	20	11655
  BCL11A-9753	-	CGAGGUAAAAGAGAUAAAGG	20	11656
  BCL11A-9754	-	ACUUGAACUUGCAGCUCAGG	20	11657
  BCL11A-9755	-	GACUAGAAGCAAAAGCGAGG	20	11658
  BCL11A-4408	+	GAGCAGGAGAGAAGGGGAGG	20	11659
  BCL11A-4594	+	AGGGGCGGGCCGAGGGGAGG	20	11660
  BCL11A-9756	+	CAAUGGCCAGUGCGGGGAGG	20	11661
  BCL11A-9757	-	UCGGCCCGCCCCUCCCCCGG	20	11662
  BCL11A-4471	+	GGCCGCAGCGAGCGCCGCGG	20	11663
  BCL11A-4661	+	CGCAGCGAGCGCCGCGGCGG	20	11664
  BCL11A-4479	+	GGCGGCGGCGGCGGCGGCGG	20	11665
  BCL11A-4448	+	GCGGGCGGCGGCGGCGGCGG	20	11666
  BCL11A-4501	+	GGGGCGGGCGGCGGCGGCGG	20	11667
  BCL11A-5484	+	UGCGGGGCGGGCGGCGGCGG	20	11668
  BCL11A-5485	+	GGCUGCGGGGCGGGCGGCGG	20	11669
  BCL11A-5486	+	GUGGGCUGCGGGGCGGGCGG	20	11670
  BCL11A-9758	+	GAGGGGGAGGUGCGGGGCGG	20	11671
  BCL11A-9759	+	GCAGGGGUGGGAGGAAAGGG	20	11672
  BCL11A-9760	-	CUUGAACUUGCAGCUCAGGG	20	11673
  BCL11A-4443	+	GCGGCGGCGGCGGCGGCGGG	20	11674
  BCL11A-5487	+	AUGGUGGGCUGCGGGGCGGG	20	11675
  BCL11A-9761	+	AGGGGGAGGUGCGGGGCGGG	20	11676
  BCL11A-4434	+	GCCGGGAGAGAAGAAAGGGG	20	11677
  BCL11A-4476	+	GGCGAGCAGGAGAGAAGGGG	20	11678
  BCL11A-9762	+	GAAGAAAGGGGUGGCAGGGG	20	11679
  BCL11A-4486	+	GGGAGGGGCGGGCCGAGGGG	20	11680
  BCL11A-4666	+	CGCGGCCCCCGGGGGAGGGG	20	11681
  BCL11A-5489	+	AGACAUGGUGGGCUGCGGGG	20	11682
  BCL11A-9763	+	AGCCAAUGGCCAGUGCGGGG	20	11683
  BCL11A-9764	+	GGGGAGGGGGAGGUGCGGGG	20	11684
  BCL11A-9765	+	UGGCCAGUGCGGGGAGGGGG	20	11685
  BCL11A-4635	+	CCAGACGCGGCCCCCGGGGG	20	11686
  BCL11A-9766	+	GGUGGGAGGAAAGGGUGGGG	20	11687
  BCL11A-9767	+	GGGUGGGAGGAAAGGGUGGG	20	11688
  BCL11A-9768	+	AAAGGGGUGGCAGGGGUGGG	20	11689
  BCL11A-9769	-	UUAGAGUCCGCGUGUGUGGG	20	11690
  BCL11A-5490	+	UUGCUUGCGGCGAGACAUGG	20	11691
  BCL11A-9770	+	GGGGUGGGAGGAAAGGGUGG	20	11692
  BCL11A-9771	+	GCCGAGGGGAGGGGGCGCUG	20	11693
  BCL11A-9772	-	CACCGCCGCGGCGCUCGCUG	20	11694
  BCL11A-5497	+	UCCCGUUUGCUUAAGUGCUG	20	11695
  BCL11A-9773	+	GGACAAGCCAAUGGCCAGUG	20	11696
  BCL11A-9774	+	AGUGCGGGGAGGGGGAGGUG	20	11697
  BCL11A-9775	+	AGGGGUGGGAGGAAAGGGUG	20	11698
  BCL11A-9776	-	UUUUAGAGUCCGCGUGUGUG	20	11699
  BCL11A-9777	+	GGCGCAGGGAAGAUGAAUUG	20	11700
  BCL11A-5500	+	GCUGGGGUUUGCCUUGCUUG	20	11701
  BCL11A-9778	+	GACAGAGACACACAAAACAU	20	11702
  BCL11A-9779	-	CCCCUCCCCGCACUGGCCAU	20	11703
  BCL11A-9780	+	ACACGGCAAUGGUUCCAGAU	20	11704
  BCL11A-9781	+	AUAAUUAUUAUUACUAUUAU	20	11705
  BCL11A-9782	-	GCCCCAGCGCCCCCUCCCCU	20	11706
  BCL11A-9783	+	GGCCGAGGGGAGGGGGCGCU	20	11707
  BCL11A-5509	+	UUCCCGUUUGCUUAAGUGCU	20	11708
  BCL11A-9784	+	CAGGGGUGGGAGGAAAGGGU	20	11709
  BCL11A-9785	+	AAGAAAGGGGUGGCAGGGGU	20	11710
  BCL11A-9786	+	GCGCAGGGAAGAUGAAUUGU	20	11711
  BCL11A-9787	+	UAAUUAUUAUUACUAUUAUU	20	11712
  BCL11A-9788	-	GUAUUAUUUCUAAUUUAUUU	20	11713

• Table 18C provides exemplary targeting domains for knocking down the BCL11A 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 1 kb 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 BCL11A gene (e.g., reduce or eliminate BCL11A gene expression, BCL11A protein function, or the level of BCL11A protein). One or more gRNA may be used to target an eiCas9 to the promoter region of the BCL11A gene.

• TABLE 18C
  	DNA		Target Site	SEQ ID
  gRNA Name	Strand	Targeting Domain	Length	NO:
  BCL11A-9789	-	CACUCACCGUAAGAAAA	17	11714
  BCL11A-9790	+	CCUCUGGCCGGAACAAA	17	11715
  BCL11A-9791	+	CGAGGAGCCGGCACAAA	17	11716
  BCL11A-9792	-	UAUUUCUCUUUUCGAAA	17	11717
  BCL11A-9793	-	GGGAGCUGGUGGGGAAA	17	11718
  BCL11A-9794	-	AAGUGGCACUGUGGAAA	17	11719
  BCL11A-9795	+	GGGCUGCGGGUCCGGAA	17	11720
  BCL11A-9796	+	GAAAUAAAGCGGCGGAA	17	11721
  BCL11A-9797	-	UGGGAGCUGGUGGGGAA	17	11722
  BCL11A-9798	-	AAAGUGGCACUGUGGAA	17	11723
  BCL11A-9799	+	GCCCGAGGGCGCCCCCA	17	11724
  BCL11A-9800	+	CGUCCUUCCCGGUCCCA	17	11725
  BCL11A-9801	+	CCCCCAAGGCCGAGCCA	17	11726
  BCL11A-9802	+	CCCGCGUGUGGACGCCA	17	11727
  BCL11A-9597	-	GUGUGUGGGGGGGAGCA	17	11728
  BCL11A-9803	+	AGGUGGGAGGGAGCGCA	17	11729
  BCL11A-9804	-	GGACACCAGCGCGCUCA	17	11730
  BCL11A-9805	+	CGCGCGGCCUGGAAAGA	17	11731
  BCL11A-9806	-	UCCGCGGAGUCGGGAGA	17	11732
  BCL11A-9807	+	CGCAGGCCGGGGCCCGA	17	11733
  BCL11A-9808	-	GAGAGGGGCCGCGGCGA	17	11734
  BCL11A-9809	+	AGCUCCGCAGCGGGCGA	17	11735
  BCL11A-9810	-	CGUGGGACCGGGAAGGA	17	11736
  BCL11A-9811	-	GGUGUGCGUACGGAGGA	17	11737
  BCL11A-9812	+	AGGGCUGCGGGUCCGGA	17	11738
  BCL11A-9813	+	GGGGAAGCGCGGGCGGA	17	11739
  BCL11A-9814	-	AAAUGGGGGGGUAGGGA	17	11740
  BCL11A-9815	-	GAGCCGUGGGACCGGGA	17	11741
  BCL11A-9816	-	CGCGGCGGCGGCGGGGA	17	11742
  BCL11A-9817	+	GGCGAGGGGAGGUGGGA	17	11743
  BCL11A-9818	+	UCCAGCCUAAGUUUGGA	17	11744
  BCL11A-9819	-	AAUAAUGAACAAUGCUA	17	11745
  BCL11A-9820	-	GGAAGUGGGUGUGCGUA	17	11746
  BCL11A-9821	-	AAGAAAAUGGGGGGGUA	17	11747
  BCL11A-9822	+	ACCCCCCCAUUUUCUUA	17	11748
  BCL11A-9823	+	UCAUUAUUUUGCAAAAC	17	11749
  BCL11A-9824	+	AUAGAGCGAGAGUGCAC	17	11750
  BCL11A-9825	-	GAGAAAAGAGGUGAGAC	17	11751
  BCL11A-9826	-	AGAGGGGCCGCGGCGAC	17	11752
  BCL11A-9827	-	GUGGGACCGGGAAGGAC	17	11753
  BCL11A-9828	+	AAGGCCGAGCCAGGGAC	17	11754
  BCL11A-9829	+	GCCUGGAAAGAGGGGAC	17	11755
  BCL11A-9830	-	GGGGAGAGCCGUGGGAC	17	11756
  BCL11A-9831	-	CAACUCACAUGCAAACC	17	11757
  BCL11A-9832	+	UAGAGCGAGAGUGCACC	17	11758
  BCL11A-9833	+	AGGCCGAGCCAGGGACC	17	11759
  BCL11A-9834	+	CCUGGAAAGAGGGGACC	17	11760
  BCL11A-9835	-	GGGAGAGCCGUGGGACC	17	11761
  BCL11A-9836	-	CCGGGAGCAACUCUACC	17	11762
  BCL11A-9837	+	CACCAGCUCCCACCCCC	17	11763
  BCL11A-9838	+	CGGGAGGCUGCAGCCCC	17	11764
  BCL11A-9839	-	GCUUUUACUUCGGCCCC	17	11765
  BCL11A-9840	-	CUGUGGAAAGGGGCCCC	17	11766
  BCL11A-9841	+	UCACCUCUUUUCUCCCC	17	11767
  BCL11A-9842	-	CCGCGCUUCCCCAGCCC	17	11768
  BCL11A-9843	+	CCGGGAGGCUGCAGCCC	17	11769
  BCL11A-9844	-	GGGGCGCCCUCGGGCCC	17	11770
  BCL11A-9845	-	CGCCGCCUGCCUCUCCC	17	11771
  BCL11A-9846	+	CUCACCUCUUUUCUCCC	17	11772
  BCL11A-9847	-	UCUAAAAAACGAUUCCC	17	11773
  BCL11A-9848	+	GCGGGCGGAGGGAAGCC	17	11774
  BCL11A-9849	-	CCCGCGCUUCCCCAGCC	17	11775
  BCL11A-9850	+	GCCCCCAAGGCCGAGCC	17	11776
  BCL11A-9851	+	CCCCGCGUGUGGACGCC	17	11777
  BCL11A-9852	+	GCGGACUCAGGAGCGCC	17	11778
  BCL11A-9853	+	GGCAGGCGGCGCAGGCC	17	11779
  BCL11A-9854	+	CAGGAGCCCGCGCGGCC	17	11780
  BCL11A-9855	-	CCGGGGCUGCAGCCUCC	17	11781
  BCL11A-9856	-	CAGGCCGCGCGGGCUCC	17	11782
  BCL11A-9857	+	CCAGGUAGAGUUGCUCC	17	11783
  BCL11A-9858	+	GCAGCGCCCAAGUCUCC	17	11784
  BCL11A-9859	-	UACGGAGGAGGGUGUCC	17	11785
  BCL11A-9860	-	GUCUAAAAAACGAUUCC	17	11786
  BCL11A-9861	+	GCGUCUCCCGUCCUUCC	17	11787
  BCL11A-9862	-	CCCGGUCCCCUCUUUCC	17	11788
  BCL11A-9863	+	AGUUACAGCUCCGCAGC	17	11789
  BCL11A-9864	+	CCGGCACAAAAGGCAGC	17	11790
  BCL11A-9865	-	ACGGUCAAGUGUGCAGC	17	11791
  BCL11A-9866	+	GGGCAAGCGCGAGGAGC	17	11792
  BCL11A-9620	-	CGUGUGUGGGGGGGAGC	17	11793
  BCL11A-9867	-	AACCUGGGGGUGGGAGC	17	11794
  BCL11A-9868	-	CCCUGGCGUCCACACGC	17	11795
  BCL11A-9869	-	UUCCCGAGCGCAGCCGC	17	11796
  BCL11A-9870	+	CCGGGCUGGGGAAGCGC	17	11797
  BCL11A-9871	+	CGCGGACUCAGGAGCGC	17	11798
  BCL11A-9872	-	CUCUUUCCAGGCCGCGC	17	11799
  BCL11A-9873	+	CUUGACCGUGAGCGCGC	17	11800
  BCL11A-9874	+	GGAGAGGCAGGCGGCGC	17	11801
  BCL11A-9875	+	AGGCAGGCGGCGCAGGC	17	11802
  BCL11A-9876	+	GGGGACCGGGGAGAGGC	17	11803
  BCL11A-9877	-	GCCCUCCAAACUUAGGC	17	11804
  BCL11A-9878	-	AGGACGGGAGACGCGGC	17	11805
  BCL11A-9879	-	GCGAGCGCGGCGGCGGC	17	11806
  BCL11A-9880	+	AGGCUGCAGCCCCGGGC	17	11807
  BCL11A-9881	+	UGCAAAACUGGCGGGGC	17	11808
  BCL11A-9882	+	UAUUUUGCAAAACUGGC	17	11809
  BCL11A-9883	+	AAACACCCACCUCUGGC	17	11810
  BCL11A-9884	+	UAAGUUUGGAGGGCUGC	17	11811
  BCL11A-9885	+	ACAAAAGGCGGCAGUGC	17	11812
  BCL11A-9886	-	CCCGCUGCCUUUUGUGC	17	11813
  BCL11A-9887	+	CCCGACUCCGCGGACUC	17	11814
  BCL11A-9888	+	GGACAAACACCCACCUC	17	11815
  BCL11A-9889	-	GCCUUGGGGGCGCCCUC	17	11816
  BCL11A-9890	-	UUUGCUGUCCUCUCCUC	17	11817
  BCL11A-9891	+	AGCCCGCGGCUGCGCUC	17	11818
  BCL11A-9892	-	AGCGCAGCCGCGGGCUC	17	11819
  BCL11A-9893	-	CCUGAGUCCGCGGAGUC	17	11820
  BCL11A-9894	+	UUGGAGGGCUGCGGGUC	17	11821
  BCL11A-9895	-	GUACGGAGGAGGGUGUC	17	11822
  BCL11A-9896	-	GCUCAGCUCUCAACUUC	17	11823
  BCL11A-9897	-	CUUGGGCGCUGCCCUUC	17	11824
  BCL11A-9898	-	ACUGCCGCCUUUUGUUC	17	11825
  BCL11A-9899	-	AUUCCCGGGGAGAAAAG	17	11826
  BCL11A-9900	-	CCACAAUAGUGAGAAAG	17	11827
  BCL11A-9901	+	GGCGGAAAGGAGGAAAG	17	11828
  BCL11A-9902	+	CCGCGCGGCCUGGAAAG	17	11829
  BCL11A-9903	-	AGUGGCACUGUGGAAAG	17	11830
  BCL11A-9904	+	CGAAAAGAGAAAUAAAG	17	11831
  BCL11A-9905	-	GCGGCGGGGAGGGGAAG	17	11832
  BCL11A-9906	+	CCGCGUGUGGACGCCAG	17	11833
  BCL11A-9907	-	CCUUUUGUUCCGGCCAG	17	11834
  BCL11A-9908	+	AAGUUACAGCUCCGCAG	17	11835
  BCL11A-9909	+	GCCGGCACAAAAGGCAG	17	11836
  BCL11A-9910	-	CACGGUCAAGUGUGCAG	17	11837
  BCL11A-9911	+	GCGCGGCCUGGAAAGAG	17	11838
  BCL11A-9912	-	CCGCGGAGUCGGGAGAG	17	11839
  BCL11A-9913	+	GCUCCGCAGCGGGCGAG	17	11840
  BCL11A-9914	+	AAACUUUGCCCGAGGAG	17	11841
  BCL11A-9915	-	GUCCGCGGAGUCGGGAG	17	11842
  BCL11A-9916	+	AAGAGGGGACCGGGGAG	17	11843
  BCL11A-9917	-	GCGGCGGCGGCGGGGAG	17	11844
  BCL11A-9918	+	GCGGGGCGGGGGGGGAG	17	11845
  BCL11A-9919	+	CAUUUUCUUACGGUGAG	17	11846
  BCL11A-9920	+	GGGAGCGCACGGCAACG	17	11847
  BCL11A-9642	+	GCUCCCCCCCACACACG	17	11848
  BCL11A-9921	-	CCCCUGGCGUCCACACG	17	11849
  BCL11A-9922	-	GGGAAGGACGGGAGACG	17	11850
  BCL11A-9923	-	GAGGGGCCGCGGCGACG	17	11851
  BCL11A-9924	+	CUGGAAAGAGGGGACCG	17	11852
  BCL11A-9925	-	CGCGCUUCCCCAGCCCG	17	11853
  BCL11A-9926	+	UAAAAGCCCCGAGCCCG	17	11854
  BCL11A-9927	+	GCGCAGGCCGGGGCCCG	17	11855
  BCL11A-9928	+	UCGGGAAACUUUGCCCG	17	11856
  BCL11A-9929	-	CUAAAAAACGAUUCCCG	17	11857
  BCL11A-9930	-	UUUCCCGAGCGCAGCCG	17	11858
  BCL11A-9931	-	GGCGACGGGGAGAGCCG	17	11859
  BCL11A-9932	+	CGGACUCAGGAGCGCCG	17	11860
  BCL11A-9933	+	GGCUCUCCCCGUCGCCG	17	11861
  BCL11A-9934	+	GCAGGCGGCGCAGGCCG	17	11862
  BCL11A-9935	-	AGUCGGGAGAGGGGCCG	17	11863
  BCL11A-9936	+	CCCCUCUCCCGACUCCG	17	11864
  BCL11A-9937	-	CGGCGCUCCUGAGUCCG	17	11865
  BCL11A-9938	+	CCCGGGCUGGGGAAGCG	17	11866
  BCL11A-9939	-	CACGCGGGGAGCGAGCG	17	11867
  BCL11A-9940	-	CCUGGCGUCCACACGCG	17	11868
  BCL11A-9941	+	GUCUCCAGGAGCCCGCG	17	11869
  BCL11A-9942	-	CCUCUUUCCAGGCCGCG	17	11870
  BCL11A-9943	+	GCGGGAGGGCAAGCGCG	17	11871
  BCL11A-9944	-	CGAGCGCGGCGGCGGCG	17	11872
  BCL11A-9945	+	CAGCUCCGCAGCGGGCG	17	11873
  BCL11A-9946	+	GCAAAACUGGCGGGGCG	17	11874
  BCL11A-9947	+	AUUUUGCAAAACUGGCG	17	11875
  BCL11A-9948	-	GCGCAGCCGCGGGCUCG	17	11876
  BCL11A-9949	+	CUGGCCGGAACAAAAGG	17	11877
  BCL11A-9950	+	AUAAAGCGGCGGAAAGG	17	11878
  BCL11A-9951	+	GACCGGGGAGAGGCAGG	17	11879
  BCL11A-9952	+	GGAAAGGAGGAAAGAGG	17	11880
  BCL11A-9953	-	UUUGUUCCGGCCAGAGG	17	11881
  BCL11A-9954	-	GGGUGUGCGUACGGAGG	17	11882
  BCL11A-9955	+	CAGCGGGCGAGGGGAGG	17	11883
  BCL11A-9956	-	AGUGGGUGUGCGUACGG	17	11884
  BCL11A-9957	+	GGACUCAGGAGCGCCGG	17	11885
  BCL11A-9958	+	AAAGAGAAAUAAAGCGG	17	11886
  BCL11A-9959	-	GCGGGGAGCGAGCGCGG	17	11887
  BCL11A-9960	-	GGGAGCGAGCGCGGCGG	17	11888
  BCL11A-9961	-	AGCGAGCGCGGCGGCGG	17	11889
  BCL11A-9962	+	UGGGGAAGCGCGGGCGG	17	11890
  BCL11A-9963	+	CAAAACUGGCGGGGCGG	17	11891
  BCL11A-9964	-	AGCUGGUGGGGAAAGGG	17	11892
  BCL11A-9965	-	AAAAUGGGGGGGUAGGG	17	11893
  BCL11A-9966	+	AGCGAGAGUGCACCGGG	17	11894
  BCL11A-9967	-	GUCAAGUGUGCAGCGGG	17	11895
  BCL11A-9968	+	GGCUGGGGAAGCGCGGG	17	11896
  BCL11A-9969	+	AAAACUGGCGGGGCGGG	17	11897
  BCL11A-9970	+	CCGCAGCGGGCGAGGGG	17	11898
  BCL11A-9971	-	GCGCGGCGGCGGCGGGG	17	11899
  BCL11A-9972	+	AAACUGGCGGGGCGGGG	17	11900
  BCL11A-9973	+	UUGCAAAACUGGCGGGG	17	11901
  BCL11A-9974	+	AACUGGCGGGGCGGGGG	17	11902
  BCL11A-9975	-	ACAUGCAAACCUGGGGG	17	11903
  BCL11A-9976	-	ACCGUAAGAAAAUGGGG	17	11904
  BCL11A-9548	-	AGUCCGCGUGUGUGGGG	17	11905
  BCL11A-9977	-	CACCGUAAGAAAAUGGG	17	11906
  BCL11A-9978	+	GGGCGAGGGGAGGUGGG	17	11907
  BCL11A-9668	-	GAGUCCGCGUGUGUGGG	17	11908
  BCL11A-9979	-	UCACCGUAAGAAAAUGG	17	11909
  BCL11A-9980	+	UUAUUUUGCAAAACUGG	17	11910
  BCL11A-9981	-	CUCACAUGCAAACCUGG	17	11911
  BCL11A-9982	-	CUGGGGGUGGGAGCUGG	17	11912
  BCL11A-9670	-	AGAGUCCGCGUGUGUGG	17	11913
  BCL11A-9983	-	GCGGAGCUGUAACUUGG	17	11914
  BCL11A-9984	-	CCCUGGCUCGGCCUUGG	17	11915
  BCL11A-9985	+	AUCCAGCCUAAGUUUGG	17	11916
  BCL11A-9986	-	CUCACCGUAAGAAAAUG	17	11917
  BCL11A-9987	-	GUGAGAAAGUGGCACUG	17	11918
  BCL11A-9988	-	ACUCACAUGCAAACCUG	17	11919
  BCL11A-9989	-	CCUCCCCUCGCCCGCUG	17	11920
  BCL11A-9990	+	CUAAGUUUGGAGGGCUG	17	11921
  BCL11A-9991	+	GCUGCAGCCCCGGGCUG	17	11922
  BCL11A-9992	+	CGCUCGCUCCCCGCGUG	17	11923
  BCL11A-9993	-	GGGGGUGGGAGCUGGUG	17	11924
  BCL11A-9678	-	UUUAGAGUCCGCGUGUG	17	11925
  BCL11A-9549	-	UAGAGUCCGCGUGUGUG	17	11926
  BCL11A-9994	+	ACUUUCUCACUAUUGUG	17	11927
  BCL11A-9995	+	CCACUUUCUCACUAUUG	17	11928
  BCL11A-9996	-	UCCCUGGCUCGGCCUUG	17	11929
  BCL11A-9997	-	ACUCACCGUAAGAAAAU	17	11930
  BCL11A-9998	-	GCUGCGGAGCUGUAACU	17	11931
  BCL11A-9999	-	GCGGGCUCCUGGAGACU	17	11932
  BCL11A-10000	-	AACUCACAUGCAAACCU	17	11933
  BCL11A-10001	-	GGCCUUGGGGGCGCCCU	17	11934
  BCL11A-10002	-	GGUCCCUGGCUCGGCCU	17	11935
  BCL11A-10003	-	CUUUGCUGUCCUCUCCU	17	11936
  BCL11A-10004	+	GAGCCCGCGGCUGCGCU	17	11937
  BCL11A-10005	+	GGCUGCAGCCCCGGGCU	17	11938
  BCL11A-10006	-	GAGCGCAGCCGCGGGCU	17	11939
  BCL11A-10007	-	CGGCGGGGAGGGGAAGU	17	11940
  BCL11A-10008	-	UCCUGAGUCCGCGGAGU	17	11941
  BCL11A-10009	+	AUUUUCUUACGGUGAGU	17	11942
  BLC11A-10010	-	GCGACGGGGAGAGCCGU	17	11943
  BCL11A-10011	-	UUGUUCCGGCCAGAGGU	17	11944
  BCL11A-10012	+	AGCGGGCGAGGGGAGGU	17	11945
  BCL11A-10013	-	UAAGAAAAUGGGGGGGU	17	11946
  BCL11A-10014	-	CAUGCAAACCUGGGGGU	17	11947
  BCL11A-10015	-	UGGGGGUGGGAGCUGGU	17	11948
  BCL11A-9687	-	UUAGAGUCCGCGUGUGU	17	11949
  BCL11A-10016	+	CACUUUCUCACUAUUGU	17	11950
  BCL11A-10017	-	CGCAGCCCUCCAAACUU	17	11951
  BCL11A-10018	-	GGCUCAGCUCUCAACUU	17	11952
  BCL11A-10019	-	CGGGCUCCUGGAGACUU	17	11953
  BCL11A-10020	-	GCUCGGGGCUUUUACUU	17	11954
  BCL11A-10021	-	GUCCCUGGCUCGGCCUU	17	11955
  BCL11A-10022	+	GGAAUCCAGCCUAAGUU	17	11956
  BCL11A-10023	-	GAGGUGAGACUGGCUUU	17	11957
  BCL11A-10024	-	UCCCACUCACCGUAAGAAAA	20	11958
  BLC11A-10025	+	CCACCUCUGGCCGGAACAAA	20	11959
  BCL11A-10026	+	GCGCGAGGAGCCGGCACAAA	20	11960
  BCL11A-10027	-	CUUUAUUUCUCUUUUCGAAA	20	11961
  BCL11A-10028	-	GGUGGGAGCUGGUGGGGAAA	20	11962
  BCL11A-10029	-	AGAAAGUGGCACUGUGGAAA	20	11963
  BCL11A-10030	+	GGAGGGCUGCGGGUCCGGAA	20	11964
  BCL11A-10031	+	AGAGAAAUAAAGCGGCGGAA	20	11965
  BCL11A-10032	-	GGGUGGGAGCUGGUGGGGAA	20	11966
  BCL11A-10033	-	GAGAAAGUGGCACUGUGGAA	20	11967
  BCL11A-10034	+	GGGGCCCGAGGGCGCCCCCA	20	11968
  BCL11A-10035	+	UCCCGUCCUUCCCGGUCCCA	20	11969
  BCL11A-10036	+	GCGCCCCCAAGGCCGAGCCA	20	11970
  BCL11A-10037	+	CUCCCCGCGUGUGGACGCCA	20	11971
  BCL11A-9701	-	CGCGUGUGUGGGGGGGAGCA	20	11972
  BCL11A-10038	+	GGGAGGUGGGAGGGAGCGCA	20	11973
  BCL11A-10039	-	UUUGGACACCAGCGCGCUCA	20	11974
  BCL11A-10040	+	GCCCGCGCGGCCUGGAAAGA	20	11975
  BCL11A-10041	-	GAGUCCGCGGAGUCGGGAGA	20	11976
  BCL11A-10042	+	CGGCGCAGGCCGGGGCCCGA	20	11977
  BCL11A-10043	-	CGGGAGAGGGGCCGCGGCGA	20	11978
  BCL11A-10044	+	UACAGCUCCGCAGCGGGCGA	20	11979
  BCL11A-10045	-	AGCCGUGGGACCGGGAAGGA	20	11980
  BCL11A-10046	-	GUGGGUGUGCGUACGGAGGA	20	11981
  BCL11A-10047	+	UGGAGGGCUGCGGGUCCGGA	20	11982
  BCL11A-10048	+	GCUGGGGAAGCGCGGGCGGA	20	11983
  BCL11A-10049	-	AGAAAAUGGGGGGGUAGGGA	20	11984
  BCL11A-10050	-	GGAGAGCCGUGGGACCGGGA	20	11985
  BCL11A-10051	-	GAGCGCGGCGGCGGCGGGGA	20	11986
  BCL11A-10052	+	GCGGGCGAGGGGAGGUGGGA	20	11987
  BCL11A-10053	+	GAAUCCAGCCUAAGUUUGGA	20	11988
  BCL11A-10054	-	CAAAAUAAUGAACAAUGCUA	20	11989
  BCL11A-10055	-	AGGGGAAGUGGGUGUGCGUA	20	11990
  BCL11A-10056	-	CGUAAGAAAAUGGGGGGGUA	20	11991
  BCL11A-10057	+	CCUACCCCCCCAUUUUCUUA	20	11992
  BCL11A-10058	+	UGUUCAUUAUUUUGCAAAAC	20	11993
  BCL11A-10059	+	AAAAUAGAGCGAGAGUGCAC	20	11994
  BCL11A-10060	-	GGGGAGAAAAGAGGUGAGAC	20	11995
  BCL11A-10061	-	GGGAGAGGGGCCGCGGCGAC	20	11996
  BCL11A-10062	-	GCCGUGGGACCGGGAAGGAC	20	11997
  BCL11A-10063	+	CCCAAGGCCGAGCCAGGGAC	20	11998
  BCL11A-10064	+	GCGGCCUGGAAAGAGGGGAC	20	11999
  BCL11A-10065	-	GACGGGGAGAGCCGUGGGAC	20	12000
  BCL11A-10066	-	GAACAACUCACAUGCAAACC	20	12001
  BCL11A-10067	+	AAAUAGAGCGAGAGUGCACC	20	12002
  BCL11A-10068	+	CCAAGGCCGAGCCAGGGACC	20	12003
  BCL11A-10069	+	CGGCCUGGAAAGAGGGGACC	20	12004
  BCL11A-10070	-	ACGGGGAGAGCCGUGGGACC	20	12005
  BCL11A-10071	-	UGUCCGGGAGCAACUCUACC	20	12006
  BCL11A-10072	+	CCCCACCAGCUCCCACCCCC	20	12007
  BCL11A-10073	+	CACCGGGAGGCUGCAGCCCC	20	12008
  BCL11A-10074	-	GGGGCUUUUACUUCGGCCCC	20	12009
  BCL11A-10075	-	GCACUGUGGAAAGGGGCCCC	20	12010
  BCL11A-10076	+	GUCUCACCUCUUUUCUCCCC	20	12011
  BCL11A-10077	-	CGCCCGCGCUUCCCCAGCCC	20	12012
  BCL11A-10078	+	GCACCGGGAGGCUGCAGCCC	20	12013
  BCL11A-10079	-	UUGGGGGCGCCCUCGGGCCC	20	12014
  BCL11A-10080	-	CUGCGCCGCCUGCCUCUCCC	20	12015
  BCL11A-10081	+	AGUCUCACCUCUUUUCUCCC	20	12016
  BCL11A-10082	-	AAGUCUAAAAAACGAUUCCC	20	12017
  BCL11A-10083	+	AGCGCGGGCGGAGGGAAGCC	20	12018
  BCL11A-10084	-	CCGCCCGCGCUUCCCCAGCC	20	12019
  BCL11A-10085	+	GGCGCCCCCAAGGCCGAGCC	20	12020
  BCL11A-10086	+	GCUCCCCGCGUGUGGACGCC	20	12021
  BCL11A-10087	+	UCCGCGGACUCAGGAGCGCC	20	12022
  BCL11A-10088	+	AGAGGCAGGCGGCGCAGGCC	20	12023
  BCL11A-10089	+	CUCCAGGAGCCCGCGCGGCC	20	12024
  BCL11A-10090	-	AGCCCGGGGCUGCAGCCUCC	20	12025
  BCL11A-10091	-	UUCCAGGCCGCGCGGGCUCC	20	12026
  BCL11A-10092	+	AAGCCAGGUAGAGUUGCUCC	20	12027
  BCL11A-10093	+	AGGGCAGCGCCCAAGUCUCC	20	12028
  BCL11A-10094	-	GCGUACGGAGGAGGGUGUCC	20	12029
  BCL11A-10095	-	CAAGUCUAAAAAACGAUUCC	20	12030
  BCL11A-10096	+	GCCGCGUCUCCCGUCCUUCC	20	12031
  BCL11A-10097	-	CUCCCCGGUCCCCUCUUUCC	20	12032
  BCL11A-10098	+	CCAAGUUACAGCUCCGCAGC	20	12033
  BCL11A-10099	+	GAGCCGGCACAAAAGGCAGC	20	12034
  BCL11A-10100	-	CUCACGGUCAAGUGUGCAGC	20	12035
  BCL11A-10101	+	GGAGGGCAAGCGCGAGGAGC	20	12036
  BCL11A-9563	-	CCGCGUGUGUGGGGGGGAGC	20	12037
  BCL11A-10102	-	GCAAACCUGGGGGUGGGAGC	20	12038
  BCL11A-10103	-	GGCCCCUGGCGUCCACACGC	20	12039
  BCL11A-10104	-	AGUUUCCCGAGCGCAGCCGC	20	12040
  BCL11A-10105	+	GCCCCGGGCUGGGGAAGCGC	20	12041
  BCL11A-10106	+	CUCCGCGGACUCAGGAGCGC	20	12042
  BCL11A-10107	-	CCCCUCUUUCCAGGCCGCGC	20	12043
  BCL11A-10108	+	ACACUUGACCGUGAGCGCGC	20	12044
  BCL11A-10109	+	CGGGGAGAGGCAGGCGGCGC	20	12045
  BCL11A-10110	+	GAGAGGCAGGCGGCGCAGGC	20	12046
  BCL11A-10111	+	AGAGGGGACCGGGGAGAGGC	20	12047
  BCL11A-10112	-	GCAGCCCUCCAAACUUAGGC	20	12048
  BCL11A-10113	-	GGAAGGACGGGAGACGCGGC	20	12049
  BCL11A-10114	-	GGAGCGAGCGCGGCGGCGGC	20	12050
  BCL11A-10115	+	GGGAGGCUGCAGCCCCGGGC	20	12051
  BCL11A-10116	+	UUUUGCAAAACUGGCGGGGC	20	12052
  BCL11A-10117	+	CAUUAUUUUGCAAAACUGGC	20	12053
  BCL11A-10118	+	GACAAACACCCACCUCUGGC	20	12054
  BCL11A-10119	+	GCCUAAGUUUGGAGGGCUGC	20	12055
  BCL11A-10120	+	GGAACAAAAGGCGGCAGUGC	20	12056
  BCL11A-10121	-	UGUCCCGCUGCCUUUUGUGC	20	12057
  BCL11A-10122	+	UCUCCCGACUCCGCGGACUC	20	12058
  BCL11A-10123	+	GCGGGACAAACACCCACCUC	20	12059
  BCL11A-10124	-	UCGGCCUUGGGGGCGCCCUC	20	12060
  BCL11A-10125	-	UUCUUUGCUGUCCUCUCCUC	20	12061
  BCL11A-10126	+	CCGAGCCCGCGGCUGCGCUC	20	12062
  BCL11A-10127	-	CCGAGCGCAGCCGCGGGCUC	20	12063
  BCL11A-10128	-	GCUCCUGAGUCCGCGGAGUC	20	12064
  BCL11A-10129	+	AGUUUGGAGGGCUGCGGGUC	20	12065
  BCL11A-10130	-	UGCGUACGGAGGAGGGUGUC	20	12066
  BCL11A-10131	-	GAGGCUCAGCUCUCAACUUC	20	12067
  BCL11A-10132	-	AGACUUGGGCGCUGCCCUUC	20	12068
  BCL11A-10133	-	GGCACUGCCGCCUUUUGUUC	20	12069
  BCL11A-10134	-	ACGAUUCCCGGGGAGAAAAG	20	12070
  BCL11A-10135	-	UCCCCACAAUAGUGAGAAAG	20	12071
  BCL11A-10136	+	AGCGGCGGAAAGGAGGAAAG	20	12072
  BCL11A-10137	+	AGCCCGCGCGGCCUGGAAAG	20	12073
  BCL11A-10138	-	GAAAGUGGCACUGUGGAAAG	20	12074
  BCL11A-10139	+	UUUCGAAAAGAGAAAUAAAG	20	12075
  BCL11A-10140	-	GCGGCGGCGGGGAGGGGAAG	20	12076
  BCL11A-10141	+	UCCCCGCGUGUGGACGCCAG	20	12077
  BCL11A-10142	-	CCGCCUUUUGUUCCGGCCAG	20	12078
  BCL11A-10143	+	UCCAAGUUACAGCUCCGCAG	20	12079
  BCL11A-10144	+	GGAGCCGGCACAAAAGGCAG	20	12080
  BCL11A-10145	-	GCUCACGGUCAAGUGUGCAG	20	12081
  BCL11A-10146	+	CCCGCGCGGCCUGGAAAGAG	20	12082
  BCL11A-10147	-	AGUCCGCGGAGUCGGGAGAG	20	12083
  BCL11A-10148	+	ACAGCUCCGCAGCGGGCGAG	20	12084
  BCL11A-10149	+	GGGAAACUUUGCCCGAGGAG	20	12085
  BCL11A-10150	-	UGAGUCCGCGGAGUCGGGAG	20	12086
  BCL11A-10151	+	GGAAAGAGGGGACCGGGGAG	20	12087
  BCL11A-10152	-	AGCGCGGCGGCGGCGGGGAG	20	12088
  BCL11A-10153	+	CUGGCGGGGCGGGGGGGGAG	20	12089
  BLC11A-10154	+	CCCCAUUUUCUUACGGUGAG	20	12090
  BCL11A-10155	+	GGAGGGAGCGCACGGCAACG	20	12091
  BCL11A-9741	+	CCUGCUCCCCCCCACACACG	20	12092
  BCL11A-10156	-	CGGCCCCUGGCGUCCACACG	20	12093
  BCL11A-10157	-	ACCGGGAAGGACGGGAGACG	20	12094
  BCL11A-10158	-	GGAGAGGGGCCGCGGCGACG	20	12095
  BCL11A-10159	+	GGCCUGGAAAGAGGGGACCG	20	12096
  BCL11A-10160	-	GCCCGCGCUUCCCCAGCCCG	20	12097
  BCL11A-10161	+	AAGUAAAAGCCCCGAGCCCG	20	12098
  BCL11A-10162	+	GCGGCGCAGGCCGGGGCCCG	20	12099
  BCL11A-10163	+	CGCUCGGGAAACUUUGCCCG	20	12100
  BCL11A-10164	-	AGUCUAAAAAACGAUUCCCG	20	12101
  BCL11A-10165	-	AAGUUUCCCGAGCGCAGCCG	20	12102
  BCL11A-10166	-	CGCGGCGACGGGGAGAGCCG	20	12103
  BCL11A-10167	+	CCGCGGACUCAGGAGCGCCG	20	12104
  BCL11A-10168	+	CACGGCUCUCCCCGUCGCCG	20	12105
  BCL11A-10169	+	GAGGCAGGCGGCGCAGGCCG	20	12106
  BCL11A-10170	-	CGGAGUCGGGAGAGGGGCCG	20	12107
  BCL11A-10171	+	CGGCCCCUCUCCCGACUCCG	20	12108
  BCL11A-10172	-	CCCCGGCGCUCCUGAGUCCG	20	12109
  BCL11A-10173	+	AGCCCCGGGCUGGGGAAGCG	20	12110
  BCL11A-10174	-	CCACACGCGGGGAGCGAGCG	20	12111
  BCL11A-10175	-	GCCCCUGGCGUCCACACGCG	20	12112
  BCL11A-10176	+	CAAGUCUCCAGGAGCCCGCG	20	12113
  BCL11A-10177	-	UCCCCUCUUUCCAGGCCGCG	20	12114
  BCL11A-10178	+	GGCGCGGGAGGGCAAGCGCG	20	12115
  BCL11A-10179	-	GAGCGAGCGCGGCGGCGGCG	20	12116
  BCL11A-10180	+	UUACAGCUCCGCAGCGGGCG	20	12117
  BCL11A-10181	+	UUUGCAAAACUGGCGGGGCG	20	12118
  BCL11A-10182	+	AUUAUUUUGCAAAACUGGCG	20	12119
  BCL11A-10183	-	CGAGCGCAGCCGCGGGCUCG	20	12120
  BCL11A-10184	+	CCUCUGGCCGGAACAAAAGG	20	12121
  BCL11A-10185	+	GAAAUAAAGCGGCGGAAAGG	20	12122
  BCL11A-10186	+	GGGGACCGGGGAGAGGCAGG	20	12123
  BCL11A-10187	+	GGCGGAAAGGAGGAAAGAGG	20	12124
  BCL11A-10188	-	CCUUUUGUUCCGGCCAGAGG	20	12125
  BCL11A-10189	-	AGUGGGUGUGCGUACGGAGG	20	12126
  BCL11A-10190	+	CCGCAGCGGGCGAGGGGAGG	20	12127
  BCL11A-10191	-	GGAAGUGGGUGUGCGUACGG	20	12128
  BCL11A-10192	+	CGCGGACUCAGGAGCGCCGG	20	12129
  BCL11A-10193	+	CGAAAAGAGAAAUAAAGCGG	20	12130
  BCL11A-10194	-	CACGCGGGGAGCGAGCGCGG	20	12131
  BLC11A-10195	-	GCGGGGAGCGAGCGCGGCGG	20	12132
  BCL11A-10196	-	GGGAGCGAGCGCGGCGGCGG	20	12133
  BCL11A-10197	+	GGCUGGGGAAGCGCGGGCGG	20	12134
  BCL11A-10198	+	UUGCAAAACUGGCGGGGCGG	20	12135
  BCL11A-10199	-	GGGAGCUGGUGGGGAAAGGG	20	12136
  BCL11A-10200	-	AAGAAAAUGGGGGGGUAGGG	20	12137
  BCL11A-10201	+	UAGAGCGAGAGUGCACCGGG	20	12138
  BCL11A-10202	-	ACGGUCAAGUGUGCAGCGGG	20	12139
  BCL11A-10203	+	CCGGGCUGGGGAAGCGCGGG	20	12140
  BCL11A-10204	+	UGCAAAACUGGCGGGGCGGG	20	12141
  BCL11A-10205	+	GCUCCGCAGCGGGCGAGGGG	20	12142
  BCL11A-10206	-	CGAGCGCGGCGGCGGCGGGG	20	12143
  BCL11A-10207	+	GCAAAACUGGCGGGGCGGGG	20	12144
  BCL11A-10208	+	AUUUUGCAAAACUGGCGGGG	20	12145
  BCL11A-10209	+	CAAAACUGGCGGGGCGGGGG	20	12146
  BCL11A-10210	-	CUCACAUGCAAACCUGGGGG	20	12147
  BCL11A-10211	-	CUCACCGUAAGAAAAUGGGG	20	12148
  BCL11A-9577	-	UAGAGUCCGCGUGUGUGGGG	20	12149
  BCL11A-10212	-	ACUCACCGUAAGAAAAUGGG	20	12150
  BCL11A-10213	+	AGCGGGCGAGGGGAGGUGGG	20	12151
  BCL11A-9769	-	UUAGAGUCCGCGUGUGUGGG	20	12152
  BCL11A-10214	-	CACUCACCGUAAGAAAAUGG	20	12153
  BCL11A-10215	+	UCAUUAUUUUGCAAAACUGG	20	12154
  BCL11A-10216	-	CAACUCACAUGCAAACCUGG	20	12155
  BCL11A-10217	-	AACCUGGGGGUGGGAGCUGG	20	12156
  BCL11A-9578	-	UUUAGAGUCCGCGUGUGUGG	20	12157
  BCL11A-10218	-	GCUGCGGAGCUGUAACUUGG	20	12158
  BCL11A-10219	-	GGUCCCUGGCUCGGCCUUGG	20	12159
  BCL11A-10220	+	GGAAUCCAGCCUAAGUUUGG	20	12160
  BCL11A-10221	-	CCACUCACCGUAAGAAAAUG	20	12161
  BCL11A-10222	-	AUAGUGAGAAAGUGGCACUG	20	12162
  BCL11A-10223	-	ACAACUCACAUGCAAACCUG	20	12163
  BCL11A-10224	-	CCACCUCCCCUCGCCCGCUG	20	12164
  BCL11A-10225	+	AGCCUAAGUUUGGAGGGCUG	20	12165
  BCL11A-10226	+	GAGGCUGCAGCCCCGGGCUG	20	12166
  BCL11A-10227	+	CCGCGCUCGCUCCCCGCGUG	20	12167
  BCL11A-10228	-	CCUGGGGGUGGGAGCUGGUG	20	12168
  BCL11A-9581	-	CAUUUUAGAGUCCGCGUGUG	20	12169
  BCL11A-9776	-	UUUUAGAGUCCGCGUGUGUG	20	12170
  BCL11A-10229	+	GCCACUUUCUCACUAUUGUG	20	12171
  BCL11A-10230	+	GUGCCACUUUCUCACUAUUG	20	12172
  BCL11A-10231	-	CGGUCCCUGGCUCGGCCUUG	20	12173
  BCL11A-10232	-	CCCACUCACCGUAAGAAAAU	20	12174
  BCL11A-10233	-	CCCGCUGCGGAGCUGUAACU	20	12175
  BCL11A-10234	-	CGCGCGGGCUCCUGGAGACU	20	12176
  BCL11A-10235	-	AACAACUCACAUGCAAACCU	20	12177
  BCL11A-10236	-	CUCGGCCUUGGGGGCGCCCU	20	12178
  BCL11A-10237	-	CCCGGUCCCUGGCUCGGCCU	20	12179
  BCL11A-10238	-	UUUCUUUGCUGUCCUCUCCU	20	12180
  BCL11A-10239	+	CCCGAGCCCGCGGCUGCGCU	20	12181
  BCL11A-10240	+	GGAGGCUGCAGCCCCGGGCU	20	12182
  BCL11A-10241	-	CCCGAGCGCAGCCGCGGGCU	20	12183
  BCL11A-10242	-	CGGCGGCGGGGAGGGGAAGU	20	12184
  BCL11A-10243	-	CGCUCCUGAGUCCGCGGAGU	20	12185
  BCL11A-10244	+	CCCAUUUUCUUACGGUGAGU	20	12186
  BCL11A-10245	-	GCGGCGACGGGGAGAGCCGU	20	12187
  BCL11A-10246	-	CUUUUGUUCCGGCCAGAGGU	20	12188
  BCL11A-10247	+	CGCAGCGGGCGAGGGGAGGU	20	12189
  BCL11A-10248	-	CCGUAAGAAAAUGGGGGGGU	20	12190
  BCL11A-10249	-	UCACAUGCAAACCUGGGGGU	20	12191
  BCL11A-10250	-	ACCUGGGGGUGGGAGCUGGU	20	12192
  BCL11A-9586	-	AUUUUAGAGUCCGCGUGUGU	20	12193
  BCL11A-10251	+	UGCCACUUUCUCACUAUUGU	20	12194
  BCL11A-10252	-	ACCCGCAGCCCUCCAAACUU	20	12195
  BCL11A-10253	-	GGAGGCUCAGCUCUCAACUU	20	12196
  BCL11A-10254	-	GCGCGGGCUCCUGGAGACUU	20	12197
  BCL11A-10255	-	CGGGCUCGGGGCUUUUACUU	20	12198
  BCL11A-10256	-	CCGGUCCCUGGCUCGGCCUU	20	12199
  BCL11A-10257	+	CGCGGAAUCCAGCCUAAGUU	20	12200
  BCL11A-10258	-	AAAGAGGUGAGACUGGCUUU	20	12201

• Table 19A provides exemplary targeting domains for knocking down the BCL11A 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 BCL11A gene (e.g., reduce or eliminate BCL11A gene expression, BCL11A protein function, or the level of BCL11A protein). One or more gRNA may be used to target an eiCas9 to the promoter region of the BCL11A gene.

• TABLE 19A
  1st Tier

  	DNA		Target Site	SEQ ID
  gRNA Name	Strand	Targeting Domain	Length	NO:
  BCL11A-10259	+	GGCGUGGCCGGGAGAGAAGAA	21	12202
  BCL11A-10260	+	UGGCGUGGCCGGGAGAGAAGAA	22	12203
  BCL11A-10261	+	GUGGCGUGGCCGGGAGAGAAGAA	23	12204
  BCL11A-10262	+	GGUGGCGUGGCCGGGAGAGAAGAA	24	12205
  BCL11A-10263	+	CACGGCAAUGGUUCCAGA	18	12206
  BCL11A-10264	+	ACACGGCAAUGGUUCCAGA	19	12207
  BCL11A-9557	+	UACACGGCAAUGGUUCCAGA	20	12208
  BCL11A-10265	+	AUACACGGCAAUGGUUCCAGA	21	12209
  BCL11A-10266	+	CAUACACGGCAAUGGUUCCAGA	22	12210
  BCL11A-10267	+	GCAUACACGGCAAUGGUUCCAGA	23	12211
  BCL11A-10268	+	UGCAUACACGGCAAUGGUUCCAGA	24	12212
  BCL11A-6258	+	UUAUUGGGUUACUUACGC	18	12213
  BCL11A-6259	+	AUUAUUGGGUUACUUACGC	19	12214
  BCL11A-6260	+	UAUUAUUGGGUUACUUACGC	20	12215
  BCL11A-6261	+	CUAUUAUUGGGUUACUUACGC	21	12216
  BCL11A-6262	+	ACUAUUAUUGGGUUACUUACGC	22	12217
  BCL11A-6263	+	UACUAUUAUUGGGUUACUUACGC	23	12218
  BCL11A-6264	+	UUACUAUUAUUGGGUUACUUACGC	24	12219
  BCL11A-10269	+	GGGAGAGAAGAAAGGGGUGGC	21	12220
  BCL11A-10270	+	CGGGAGAGAAGAAAGGGGUGGC	22	12221
  BCL11A-10271	+	CCGGGAGAGAAGAAAGGGGUGGC	23	12222
  BCL11A-10272	+	GCCGGGAGAGAAGAAAGGGGUGGC	24	12223
  BCL11A-6265	+	UCCCGUUUGCUUAAGUGC	18	12224
  BCL11A-6266	+	UUCCCGUUUGCUUAAGUGC	19	12225
  BCL11A-5352	+	AUUCCCGUUUGCUUAAGUGC	20	12226
  BCL11A-6267	+	AAUUCCCGUUUGCUUAAGUGC	21	12227
  BCL11A-6268	+	GAAUUCCCGUUUGCUUAAGUGC	22	12228
  BCL11A-6269	+	AGAAUUCCCGUUUGCUUAAGUGC	23	12229
  BCL11A-6270	+	GAGAAUUCCCGUUUGCUUAAGUGC	24	12230
  BCL11A-10273	+	CCUGCGAACUUGAACGUC	18	12231
  BCL11A-10274	+	CCCUGCGAACUUGAACGUC	19	12232
  BCL11A-9570	+	UCCCUGCGAACUUGAACGUC	20	12233
  BCL11A-10275	+	GUCCCUGCGAACUUGAACGUC	21	12234
  BCL11A-10276	+	CGUCCCUGCGAACUUGAACGUC	22	12235
  BCL11A-10277	+	ACGUCCCUGCGAACUUGAACGUC	23	12236
  BCL11A-10278	+	GACGUCCCUGCGAACUUGAACGUC	24	12237
  BCL11A-10279	+	UACAAAGAUGGCGCAGGGAAG	21	12238
  BCL11A-10280	+	AUACAAAGAUGGCGCAGGGAAG	22	12239
  BCL11A-10281	+	AAUACAAAGAUGGCGCAGGGAAG	23	12240
  BCL11A-10282	+	UAAUACAAAGAUGGCGCAGGGAAG	24	12241
  BCL11A-10283	+	CGGUUCACAUCGGGAGAG	18	12242
  BCL11A-10284	+	UCGGUUCACAUCGGGAGAG	19	12243
  BCL11A-10285	+	CUCGGUUCACAUCGGGAGAG	20	12244
  BCL11A-10286	+	GCUCGGUUCACAUCGGGAGAG	21	12245
  BCL11A-10287	+	GGCUCGGUUCACAUCGGGAGAG	22	12246
  BCL11A-10288	+	CGGCUCGGUUCACAUCGGGAGAG	23	12247
  BCL11A-10289	+	ACGGCUCGGUUCACAUCGGGAGAG	24	12248
  BCL11A-10290	+	AAUGGUUCCAGAUGGGAU	18	12249
  BCL11A-10291	+	CAAUGGUUCCAGAUGGGAU	19	12250
  BCL11A-10292	+	GCAAUGGUUCCAGAUGGGAU	20	12251
  BCL11A-10293	+	GGCAAUGGUUCCAGAUGGGAU	21	12252
  BCL11A-10294	+	CGGCAAUGGUUCCAGAUGGGAU	22	12253
  BCL11A-10295	+	ACGGCAAUGGUUCCAGAUGGGAU	23	12254
  BCL11A-10296	+	CACGGCAAUGGUUCCAGAUGGGAU	24	12255
  BCL11A-10297	+	AACUUGAACGUCAGGAGU	18	12256
  BCL11A-10298	+	GAACUUGAACGUCAGGAGU	19	12257
  BCL11A-10299	+	CGAACUUGAACGUCAGGAGU	20	12258
  BCL11A-10300	+	GCGAACUUGAACGUCAGGAGU	21	12259
  BCL11A-10301	+	UGCGAACUUGAACGUCAGGAGU	22	12260
  BCL11A-10302	+	CUGCGAACUUGAACGUCAGGAGU	23	12261
  BCL11A-10303	+	CCUGCGAACUUGAACGUCAGGAGU	24	12262
  BCL11A-6304	-	AACCCCAGCACUUAAGCAAAC	21	12263
  BCL11A-6305	-	AAACCCCAGCACUUAAGCAAAC	22	12264
  BCL11A-6306	-	CAAACCCCAGCACUUAAGCAAAC	23	12265
  BCL11A-6307	-	GCAAACCCCAGCACUUAAGCAAAC	24	12266
  BCL11A-10304	-	AAGCAAAAGCGAGGGGGAGAG	21	12267
  BCL11A-10305	-	GAAGCAAAAGCGAGGGGGAGAG	22	12268
  BCL11A-10306	-	AGAAGCAAAAGCGAGGGGGAGAG	23	12269
  BCL11A-10307	-	UAGAAGCAAAAGCGAGGGGGAGAG	24	12270

• Table 19B provides exemplary targeting domains for knocking down the BCL11A 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 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 BCL11A gene (e.g., reduce or eliminate BCL11A gene expression, BCL11A protein function, or the level of BCL11A protein). One or more gRNA may be used to target an eiCas9 to the promoter region of the BCL11A gene.

• TABLE 19B
  2nd Tier

  			Target
  	DNA		Site	SEQ
  gRNA Name	Strand	Targeting Domain	Length	ID NO:
  BCL11A-10308	+	GUGGCCGGGAGAGAAGAA	18	12271
  BCL11A-10309	+	CGUGGCCGGGAGAGAAGAA	19	12272
  BCL11A-9697	+	GCGUGGCCGGGAGAGAAGAA	20	12273
  BCL11A-10310	+	GUGGCAGGGGUGGGAGGA	18	12274
  BCL11A-10311	+	GGUGGCAGGGGUGGGAGGA	19	12275
  BCL11A-10312	+	GGGUGGCAGGGGUGGGAGGA	20	12276
  BCL11A-10313	+	GGGGUGGCAGGGGUGGGAGGA	21	12277
  BCL11A-10314	+	AGGGGUGGCAGGGGUGGGAGGA	22	12278
  BCL11A-10315	+	AAGGGGUGGCAGGGGUGGGAGGA	23	12279
  BCL11A-10316	+	AAAGGGGUGGCAGGGGUGGGAGGA	24	12280
  BCL11A-10317	+	UAAUUAUUAUUACUAUUA	18	12281
  BCL11A-10318	+	AUAAUUAUUAUUACUAUUA	19	12282
  BCL11A-10319	+	AAUAAUUAUUAUUACUAUUA	20	12283
  BCL11A-10320	+	UAAUAAUUAUUAUUACUAUUA	21	12284
  BCL11A-10321	+	UUAAUAAUUAUUAUUACUAUUA	22	12285
  BCL11A-10322	+	AUUAAUAAUUAUUAUUACUAUUA	23	12286
  BCL11A-10323	+	UAUUAAUAAUUAUUAUUACUAUUA	24	12287
  BCL11A-10324	+	AGAGAAGAAAGGGGUGGC	18	12288
  BCL11A-10325	+	GAGAGAAGAAAGGGGUGGC	19	12289
  BCL11A-9726	+	GGAGAGAAGAAAGGGGUGGC	20	12290
  BCL11A-10326	+	AAAGAUGGCGCAGGGAAG	18	12291
  BCL11A-10327	+	CAAAGAUGGCGCAGGGAAG	19	12292
  BCL11A-10328	+	ACAAAGAUGGCGCAGGGAAG	20	12293
  BCL11A-6350	-	CCCAGCACUUAAGCAAAC	18	12294
  BCL11A-6351	-	CCCCAGCACUUAAGCAAAC	19	12295
  BCL11A-5458	-	ACCCCAGCACUUAAGCAAAC	20	12296
  BCL11A-10329	-	UUCACGAGAAAAACCUCC	18	12297
  BCL11A-10330	-	UUUCACGAGAAAAACCUCC	19	12298
  BCL11A-10331	-	UUUUCACGAGAAAAACCUCC	20	12299
  BCL11A-10332	-	UUUUUCACGAGAAAAACCUCC	21	12300
  BCL11A-10333	-	AUUUUUCACGAGAAAAACCUCC	22	12301
  BCL11A-10334	-	AAUUUUUCACGAGAAAAACCUCC	23	12302
  BCL11A-10335	-	AAAUUUUUCACGAGAAAAACCUCC	24	12303
  BCL11A-10336	-	UGAUGAAGAUAUUUUCUC	18	12304
  BCL11A-10337	-	CUGAUGAAGAUAUUUUCUC	19	12305
  BCL11A-9731	-	ACUGAUGAAGAUAUUUUCUC	20	12306
  BCL11A-10338	-	CACUGAUGAAGAUAUUUUCUC	21	12307
  BCL11A-10339	-	GCACUGAUGAAGAUAUUUUCUC	22	12308
  BCL11A-10340	-	GGCACUGAUGAAGAUAUUUUCUC	23	12309
  BCL11A-10341	-	AGGCACUGAUGAAGAUAUUUUCUC	24	12310
  BCL11A-10342	-	CAAAAGCGAGGGGGAGAG	18	12311
  BCL11A-10343	-	GCAAAAGCGAGGGGGAGAG	19	12312
  BCL11A-4583	-	AGCAAAAGCGAGGGGGAGAG	20	12313
  BCL11A-10344	-	UAUUAUUUCUAAUUUAUU	18	12314
  BCL11A-10345	-	GUAUUAUUUCUAAUUUAUU	19	12315
  BCL11A-10346	-	UGUAUUAUUUCUAAUUUAUU	20	12316
  BCL11A-10347	-	UUGUAUUAUUUCUAAUUUAUU	21	12317
  BCL11A-10348	-	UUUGUAUUAUUUCUAAUUUAUU	22	12318
  BCL11A-10349	-	CUUUGUAUUAUUUCUAAUUUAUU	23	12319
  BCL11A-10350	-	UCUUUGUAUUAUUUCUAAUUUAUU	24	12320
  BCL11A-10351	-	UUGAAUAAUCUUUCAUUU	18	12321
  BCL11A-10352	-	UUUGAAUAAUCUUUCAUUU	19	12322
  BCL11A-10353	-	UUUUGAAUAAUCUUUCAUUU	20	12323
  BCL11A-10354	-	UUUUUGAAUAAUCUUUCAUUU	21	12324
  BCL11A-10355	-	UUUUUUGAAUAAUCUUUCAUUU	22	12325
  BCL11A-10356	-	CUUUUUUGAAUAAUCUUUCAUUU	23	12326
  BCL11A-10357	-	UCUUUUUUGAAUAAUCUUUCAUUU	24	12327

• Table 19C provides exemplary targeting domains for knocking down the BCL11A 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 BCL11A gene (e.g., reduce or eliminate BCL11A gene expression, BCL11A protein function, or the level of BCL11A protein). One or more gRNA may be used

• TABLE 19C
  3rd Tier

  			Target
  	DNA		Site	SEQ
  gRNA Name	Strand	Targeting Domain	Length	ID NO:
  BCL11A-10358	+	AAAAAAAAAAAAAAAAAA	18	12328
  BCL11A-10359	+	AAAAAAAAAAAAAAAAAAA	19	12329
  BCL11A-4899	+	AAAAAAAAAAAAAAAAAAAA	20	12330
  BCL11A-10360	+	AAAAAAAAAAAAAAAAAAAAA	21	12331
  BCL11A-10361	+	AAAAAAAAAAAAAAAAAAAAAA	22	12332
  BCL11A-10362	+	AAAAAAAAAAAAAAAAAAAAAAA	23	12333
  BCL11A-10363	+	AAAAAAAAAAAAAAAAAAAAAAAA	24	12334
  BCL11A-10364	+	CAGGGGCUGGACAUGAAA	18	12335
  BCL11A-10365	+	UCAGGGGCUGGACAUGAAA	19	12336
  BCL11A-10366	+	AUCAGGGGCUGGACAUGAAA	20	12337
  BCL11A-10367	+	CAUCAGGGGCUGGACAUGAAA	21	12338
  BCL11A-10368	+	ACAUCAGGGGCUGGACAUGAAA	22	12339
  BCL11A-10369	+	CACAUCAGGGGCUGGACAUGAAA	23	12340
  BCL11A-10370	+	ACACAUCAGGGGCUGGACAUGAAA	24	12341
  BCL11A-10371	+	ACACACGCGGACUCUAAA	18	12342
  BCL11A-10372	+	CACACACGCGGACUCUAAA	19	12343
  BCL11A-10373	+	CCACACACGCGGACUCUAAA	20	12344
  BCL11A-10374	+	CCCACACACGCGGACUCUAAA	21	12345
  BCL11A-10375	+	CCCCACACACGCGGACUCUAAA	22	12346
  BCL11A-10376	+	CCCCCACACACGCGGACUCUAAA	23	12347
  BCL11A-10377	+	CCCCCCACACACGCGGACUCUAAA	24	12348
  BCL11A-10378	+	AGAGGGAGAGAGAGAGAA	18	12349
  BCL11A-10379	+	AAGAGGGAGAGAGAGAGAA	19	12350
  BCL11A-4921	+	AAAGAGGGAGAGAGAGAGAA	20	12351
  BCL11A-10380	+	AAAAGAGGGAGAGAGAGAGAA	21	12352
  BCL11A-10381	+	AAAAAGAGGGAGAGAGAGAGAA	22	12353
  BCL11A-10382	+	AAAAAAGAGGGAGAGAGAGAGAA	23	12354
  BCL11A-10383	+	AAAAAAAGAGGGAGAGAGAGAGAA	24	12355
  BCL11A-10384	+	AGGGCGAGCAGGAGAGAA	18	12356
  BCL11A-10385	+	CAGGGCGAGCAGGAGAGAA	19	12357
  BCL11A-4422	+	GCAGGGCGAGCAGGAGAGAA	20	12358
  BCL11A-10386	+	GGCAGGGCGAGCAGGAGAGAA	21	12359
  BCL11A-10387	+	GGGCAGGGCGAGCAGGAGAGAA	22	12360
  BCL11A-10388	+	UGGGCAGGGCGAGCAGGAGAGAA	23	12361
  BCL11A-10389	+	AUGGGCAGGGCGAGCAGGAGAGAA	24	12362
  BCL11A-10390	+	GAGAAGGGGAGGAGGGAA	18	12363
  BCL11A-10391	+	AGAGAAGGGGAGGAGGGAA	19	12364
  BCL11A-4404	+	GAGAGAAGGGGAGGAGGGAA	20	12365
  BCL11A-10392	+	GGAGAGAAGGGGAGGAGGGAA	21	12366
  BCL11A-10393	+	AGGAGAGAAGGGGAGGAGGGAA	22	12367
  BCL11A-10394	+	CAGGAGAGAAGGGGAGGAGGGAA	23	12368
  BCL11A-10395	+	GCAGGAGAGAAGGGGAGGAGGGAA	24	12369
  BCL11A-10396	+	ACGACGGCUCGGUUCACA	18	12370
  BCL11A-10397	+	GACGACGGCUCGGUUCACA	19	12371
  BCL11A-10398	+	GGACGACGGCUCGGUUCACA	20	12372
  BCL11A-10399	+	CGGACGACGGCUCGGUUCACA	21	12373
  BCL11A-10400	+	GCGGACGACGGCUCGGUUCACA	22	12374
  BCL11A-10401	+	GGCGGACGACGGCUCGGUUCACA	23	12375
  BCL11A-10402	+	GGGCGGACGACGGCUCGGUUCACA	24	12376
  BCL11A-10403	+	AAGGGGAAGCUCACACCA	18	12377
  BCL11A-10404	+	GAAGGGGAAGCUCACACCA	19	12378
  BCL11A-10405	+	GGAAGGGGAAGCUCACACCA	20	12379
  BCL11A-10406	+	GGGAAGGGGAAGCUCACACCA	21	12380
  BCL11A-10407	+	AGGGAAGGGGAAGCUCACACCA	22	12381
  BCL11A-10408	+	GAGGGAAGGGGAAGCUCACACCA	23	12382
  BCL11A-10409	+	GGAGGGAAGGGGAAGCUCACACCA	24	12383
  BCL11A-10410	+	AGAAAGAAGGAGACUCCA	18	12384
  BCL11A-10411	+	UAGAAAGAAGGAGACUCCA	19	12385
  BCL11A-10412	+	UUAGAAAGAAGGAGACUCCA	20	12386
  BCL11A-10413	+	GUUAGAAAGAAGGAGACUCCA	21	12387
  BCL11A-10414	+	GGUUAGAAAGAAGGAGACUCCA	22	12388
  BCL11A-10415	+	GGGUUAGAAAGAAGGAGACUCCA	23	12389
  BCL11A-10416	+	CGGGUUAGAAAGAAGGAGACUCCA	24	12390
  BCL11A-10417	+	GGCUCACCAGUGGCCGCA	18	12391
  BCL11A-10418	+	GGGCUCACCAGUGGCCGCA	19	12392
  BCL11A-10419	+	CGGGCUCACCAGUGGCCGCA	20	12393
  BCL11A-10420	+	GCGGGCUCACCAGUGGCCGCA	21	12394
  BCL11A-10421	+	CGCGGGCUCACCAGUGGCCGCA	22	12395
  BCL11A-10422	+	CCGCGGGCUCACCAGUGGCCGCA	23	12396
  BCL11A-10423	+	GCCGCGGGCUCACCAGUGGCCGCA	24	12397
  BCL11A-10424	+	UAAUACAAAGAUGGCGCA	18	12398
  BCL11A-10425	+	AUAAUACAAAGAUGGCGCA	19	12399
  BCL11A-9702	+	AAUAAUACAAAGAUGGCGCA	20	12400
  BCL11A-10426	+	AAAUAAUACAAAGAUGGCGCA	21	12401
  BCL11A-10427	+	GAAAUAAUACAAAGAUGGCGCA	22	12402
  BCL11A-10428	+	AGAAAUAAUACAAAGAUGGCGCA	23	12403
  BCL11A-10429	+	UAGAAAUAAUACAAAGAUGGCGCA	24	12404
  BCL11A-10430	+	AAAAAAAAAAAAAAAAGA	18	12405
  BCL11A-10431	+	AAAAAAAAAAAAAAAAAGA	19	12406
  BCL11A-4527	+	AAAAAAAAAAAAAAAAAAGA	20	12407
  BCL11A-10432	+	AAAAAAAAAAAAAAAAAAAGA	21	12408
  BCL11A-10433	+	AAAAAAAAAAAAAAAAAAAAGA	22	12409
  BCL11A-10434	+	AAAAAAAAAAAAAAAAAAAAAGA	23	12410
  BCL11A-10435	+	AAAAAAAAAAAAAAAAAAAAAAGA	24	12411
  BCL11A-10436	+	AGAGCCGGGUUAGAAAGA	18	12412
  BCL11A-10437	+	GAGAGCCGGGUUAGAAAGA	19	12413
  BCL11A-9708	+	GGAGAGCCGGGUUAGAAAGA	20	12414
  BCL11A-10438	+	GGGAGAGCCGGGUUAGAAAGA	21	12415
  BCL11A-10439	+	CGGGAGAGCCGGGUUAGAAAGA	22	12416
  BCL11A-10440	+	UCGGGAGAGCCGGGUUAGAAAGA	23	12417
  BCL11A-10441	+	AUCGGGAGAGCCGGGUUAGAAAGA	24	12418
  BCL11A-10442	+	CGUGGCCGGGAGAGAAGA	18	12419
  BCL11A-10443	+	GCGUGGCCGGGAGAGAAGA	19	12420
  BCL11A-10444	+	GGCGUGGCCGGGAGAGAAGA	20	12421
  BCL11A-10445	+	UGGCGUGGCCGGGAGAGAAGA	21	12422
  BCL11A-10446	+	GUGGCGUGGCCGGGAGAGAAGA	22	12423
  BCL11A-10447	+	GGUGGCGUGGCCGGGAGAGAAGA	23	12424
  BCL11A-10448	+	CGGUGGCGUGGCCGGGAGAGAAGA	24	12425
  BCL11A-10449	+	AGAGAGAGAGAAGAGAGA	18	12426
  BCL11A-10450	+	GAGAGAGAGAGAAGAGAGA	19	12427
  BCL11A-4845	+	GGAGAGAGAGAGAAGAGAGA	20	12428
  BCL11A-10451	+	GGGAGAGAGAGAGAAGAGAGA	21	12429
  BCL11A-10452	+	AGGGAGAGAGAGAGAAGAGAGA	22	12430
  BCL11A-10453	+	GAGGGAGAGAGAGAGAAGAGAGA	23	12431
  BCL11A-10454	+	AGAGGGAGAGAGAGAGAAGAGAGA	24	12432
  BCL11A-10455	+	UAGAGGGAGAGAGAGAGA	18	12433
  BCL11A-10456	+	AUAGAGGGAGAGAGAGAGA	19	12434
  BCL11A-10457	+	GAUAGAGGGAGAGAGAGAGA	20	12435
  BCL11A-10458	+	AGAUAGAGGGAGAGAGAGAGA	21	12436
  BCL11A-10459	+	GAGAUAGAGGGAGAGAGAGAGA	22	12437
  BCL11A-10460	+	AGAGAUAGAGGGAGAGAGAGAGA	23	12438
  BCL11A-10461	+	GAGAGAUAGAGGGAGAGAGAGAGA	24	12439
  BCL11A-10462	+	GAUAGAGGGAGAGAGAGA	18	12440
  BCL11A-10463	+	AGAUAGAGGGAGAGAGAGA	19	12441
  BCL11A-10464	+	GAGAUAGAGGGAGAGAGAGA	20	12442
  BCL11A-10465	+	AGAGAUAGAGGGAGAGAGAGA	21	12443
  BCL11A-10466	+	GAGAGAUAGAGGGAGAGAGAGA	22	12444
  BCL11A-10467	+	AGAGAGAUAGAGGGAGAGAGAGA	23	12445
  BCL11A-10468	+	AAGAGAGAUAGAGGGAGAGAGAGA	24	12446
  BCL11A-10469	+	AAAAAAGAGGGAGAGAGA	18	12447
  BCL11A-10470	+	AAAAAAAGAGGGAGAGAGA	19	12448
  BCL11A-4911	+	AAAAAAAAGAGGGAGAGAGA	20	12449
  BCL11A-10471	+	AAAAAAAAAGAGGGAGAGAGA	21	12450
  BCL11A-10472	+	AAAAAAAAAAGAGGGAGAGAGA	22	12451
  BCL11A-10473	+	AAAAAAAAAAAGAGGGAGAGAGA	23	12452
  BCL11A-10474	+	AAAAAAAAAAAAGAGGGAGAGAGA	24	12453
  BCL11A-10475	+	GAGAUAGAGGGAGAGAGA	18	12454
  BCL11A-10476	+	AGAGAUAGAGGGAGAGAGA	19	12455
  BCL11A-10477	+	GAGAGAUAGAGGGAGAGAGA	20	12456
  BCL11A-10478	+	AGAGAGAUAGAGGGAGAGAGA	21	12457
  BCL11A-10479	+	AAGAGAGAUAGAGGGAGAGAGA	22	12458
  BCL11A-10480	+	GAAGAGAGAUAGAGGGAGAGAGA	23	12459
  BCL11A-10481	+	AGAAGAGAGAUAGAGGGAGAGAGA	24	12460
  BCL11A-10482	+	CAGGGCGAGCAGGAGAGA	18	12461
  BCL11A-10483	+	GCAGGGCGAGCAGGAGAGA	19	12462
  BCL11A-4464	+	GGCAGGGCGAGCAGGAGAGA	20	12463
  BCL11A-10484	+	GGGCAGGGCGAGCAGGAGAGA	21	12464
  BCL11A-10485	+	UGGGCAGGGCGAGCAGGAGAGA	22	12465
  BCL11A-10486	+	AUGGGCAGGGCGAGCAGGAGAGA	23	12466
  BCL11A-10487	+	CAUGGGCAGGGCGAGCAGGAGAGA	24	12467
  BCL11A-10488	+	AAAAAAAAGAGGGAGAGA	18	12468
  BCL11A-10489	+	AAAAAAAAAGAGGGAGAGA	19	12469
  BCL11A-4909	+	AAAAAAAAAAGAGGGAGAGA	20	12470
  BCL11A-10490	+	AAAAAAAAAAAGAGGGAGAGA	21	12471
  BCL11A-10491	+	AAAAAAAAAAAAGAGGGAGAGA	22	12472
  BCL11A-10492	+	AAAAAAAAAAAAAGAGGGAGAGA	23	12473
  BCL11A-10493	+	AAAAAAAAAAAAAAGAGGGAGAGA	24	12474
  BCL11A-10494	+	GAGAGAUAGAGGGAGAGA	18	12475
  BCL11A-10495	+	AGAGAGAUAGAGGGAGAGA	19	12476
  BCL11A-10496	+	AAGAGAGAUAGAGGGAGAGA	20	12477
  BCL11A-10497	+	GAAGAGAGAUAGAGGGAGAGA	21	12478
  BCL11A-10498	+	AGAAGAGAGAUAGAGGGAGAGA	22	12479
  BCL11A-10499	+	GAGAAGAGAGAUAGAGGGAGAGA	23	12480
  BCL11A-10500	+	AGAGAAGAGAGAUAGAGGGAGAGA	24	12481
  BCL11A-10501	+	AAAAAAAAAAGAGGGAGA	18	12482
  BCL11A-10502	+	AAAAAAAAAAAGAGGGAGA	19	12483
  BCL11A-4907	+	AAAAAAAAAAAAGAGGGAGA	20	12484
  BCL11A-10503	+	AAAAAAAAAAAAAGAGGGAGA	21	12485
  BCL11A-10504	+	AAAAAAAAAAAAAAGAGGGAGA	22	12486
  BCL11A-10505	+	AAAAAAAAAAAAAAAGAGGGAGA	23	12487
  BCL11A-10506	+	AAAAAAAAAAAAAAAAGAGGGAGA	24	12488
  BCL11A-10507	+	AAGAGAGAUAGAGGGAGA	18	12489
  BCL11A-10508	+	GAAGAGAGAUAGAGGGAGA	19	12490
  BCL11A-10509	+	AGAAGAGAGAUAGAGGGAGA	20	12491
  BCL11A-10510	+	GAGAAGAGAGAUAGAGGGAGA	21	12492
  BCL11A-10511	+	AGAGAAGAGAGAUAGAGGGAGA	22	12493
  BCL11A-10512	+	GAGAGAAGAGAGAUAGAGGGAGA	23	12494
  BCL11A-10513	+	AGAGAGAAGAGAGAUAGAGGGAGA	24	12495
  BCL11A-10514	+	AGAGAGAAGAGAGAUAGA	18	12496
  BCL11A-10515	+	GAGAGAGAAGAGAGAUAGA	19	12497
  BCL11A-9709	+	AGAGAGAGAAGAGAGAUAGA	20	12498
  BCL11A-10516	+	GAGAGAGAGAAGAGAGAUAGA	21	12499
  BCL11A-10517	+	AGAGAGAGAGAAGAGAGAUAGA	22	12500
  BCL11A-10518	+	GAGAGAGAGAGAAGAGAGAUAGA	23	12501
  BCL11A-10519	+	GGAGAGAGAGAGAAGAGAGAUAGA	24	12502
  BCL11A-10520	+	CGGGAGAGCCGGGUUAGA	18	12503
  BCL11A-10521	+	UCGGGAGAGCCGGGUUAGA	19	12504
  BCL11A-10522	+	AUCGGGAGAGCCGGGUUAGA	20	12505
  BCL11A-10523	+	CAUCGGGAGAGCCGGGUUAGA	21	12506
  BCL11A-10524	+	ACAUCGGGAGAGCCGGGUUAGA	22	12507
  BCL11A-10525	+	CACAUCGGGAGAGCCGGGUUAGA	23	12508
  BCL11A-10526	+	UCACAUCGGGAGAGCCGGGUUAGA	24	12509
  BCL11A-10527	+	GGGGGAGGGGCGGGCCGA	18	12510
  BCL11A-10528	+	CGGGGGAGGGGCGGGCCGA	19	12511
  BCL11A-4648	+	CCGGGGGAGGGGCGGGCCGA	20	12512
  BCL11A-10529	+	CCCGGGGGAGGGGCGGGCCGA	21	12513
  BCL11A-10530	+	CCCCGGGGGAGGGGCGGGCCGA	22	12514
  BCL11A-10531	+	CCCCCGGGGGAGGGGCGGGCCGA	23	12515
  BCL11A-10532	+	GCCCCCGGGGGAGGGGCGGGCCGA	24	12516
  BCL11A-10533	+	UGGGCAGGGCGAGCAGGA	18	12517
  BCL11A-10534	+	AUGGGCAGGGCGAGCAGGA	19	12518
  BCL11A-10535	+	CAUGGGCAGGGCGAGCAGGA	20	12519
  BCL11A-10536	+	ACAUGGGCAGGGCGAGCAGGA	21	12520
  BCL11A-10537	+	AACAUGGGCAGGGCGAGCAGGA	22	12521
  BCL11A-10538	+	AAACAUGGGCAGGGCGAGCAGGA	23	12522
  BCL11A-10539	+	AAAACAUGGGCAGGGCGAGCAGGA	24	12523
  BCL11A-10540	+	CAGGAGAGAAGGGGAGGA	18	12524
  BCL11A-10541	+	GCAGGAGAGAAGGGGAGGA	19	12525
  BCL11A-4584	+	AGCAGGAGAGAAGGGGAGGA	20	12526
  BCL11A-10542	+	GAGCAGGAGAGAAGGGGAGGA	21	12527
  BCL11A-10543	+	CGAGCAGGAGAGAAGGGGAGGA	22	12528
  BCL11A-10544	+	GCGAGCAGGAGAGAAGGGGAGGA	23	12529
  BCL11A-10545	+	GGCGAGCAGGAGAGAAGGGGAGGA	24	12530
  BCL11A-10546	+	AAAAAAAAAAAAGAGGGA	18	12531
  BCL11A-10547	+	AAAAAAAAAAAAAGAGGGA	19	12532
  BCL11A-4905	+	AAAAAAAAAAAAAAGAGGGA	20	12533
  BCL11A-10548	+	AAAAAAAAAAAAAAAGAGGGA	21	12534
  BCL11A-10549	+	AAAAAAAAAAAAAAAAGAGGGA	22	12535
  BCL11A-10550	+	AAAAAAAAAAAAAAAAAGAGGGA	23	12536
  BCL11A-10551	+	AAAAAAAAAAAAAAAAAAGAGGGA	24	12537
  BCL11A-10552	+	AGAAGAGAGAUAGAGGGA	18	12538
  BCL11A-10553	+	GAGAAGAGAGAUAGAGGGA	19	12539
  BCL11A-10554	+	AGAGAAGAGAGAUAGAGGGA	20	12540
  BCL11A-10555	+	GAGAGAAGAGAGAUAGAGGGA	21	12541
  BCL11A-10556	+	AGAGAGAAGAGAGAUAGAGGGA	22	12542
  BCL11A-10557	+	GAGAGAGAAGAGAGAUAGAGGGA	23	12543
  BCL11A-10558	+	AGAGAGAGAAGAGAGAUAGAGGGA	24	12544
  BCL11A-10559	+	AGAGAAGGGGAGGAGGGA	18	12545
  BCL11A-10560	+	GAGAGAAGGGGAGGAGGGA	19	12546
  BCL11A-4459	+	GGAGAGAAGGGGAGGAGGGA	20	12547
  BCL11A-10561	+	AGGAGAGAAGGGGAGGAGGGA	21	12548
  BCL11A-10562	+	CAGGAGAGAAGGGGAGGAGGGA	22	12549
  BCL11A-10563	+	GCAGGAGAGAAGGGGAGGAGGGA	23	12550
  BCL11A-10564	+	AGCAGGAGAGAAGGGGAGGAGGGA	24	12551
  BCL11A-10565	+	GCGGUGGCGUGGCCGGGA	18	12552
  BCL11A-10566	+	GGCGGUGGCGUGGCCGGGA	19	12553
  BCL11A-10567	+	CGGCGGUGGCGUGGCCGGGA	20	12554
  BCL11A-10568	+	GCGGCGGUGGCGUGGCCGGGA	21	12555
  BCL11A-10569	+	CGCGGCGGUGGCGUGGCCGGGA	22	12556
  BCL11A-10570	+	CCGCGGCGGUGGCGUGGCCGGGA	23	12557
  BCL11A-10571	+	GCCGCGGCGGUGGCGUGGCCGGGA	24	12558
  BCL11A-10572	+	AGGGGCGGGCCGAGGGGA	18	12559
  BCL11A-10573	+	GAGGGGCGGGCCGAGGGGA	19	12560
  BCL11A-4461	+	GGAGGGGCGGGCCGAGGGGA	20	12561
  BCL11A-10574	+	GGGAGGGGCGGGCCGAGGGGA	21	12562
  BCL11A-10575	+	GGGGAGGGGCGGGCCGAGGGGA	22	12563
  BCL11A-10576	+	GGGGGAGGGGCGGGCCGAGGGGA	23	12564
  BCL11A-10577	+	CGGGGGAGGGGCGGGCCGAGGGGA	24	12565
  BCL11A-10578	+	CAAUGGCCAGUGCGGGGA	18	12566
  BCL11A-10579	+	CCAAUGGCCAGUGCGGGGA	19	12567
  BCL11A-9558	+	GCCAAUGGCCAGUGCGGGGA	20	12568
  BCL11A-10580	+	AGCCAAUGGCCAGUGCGGGGA	21	12569
  BCL11A-10581	+	AAGCCAAUGGCCAGUGCGGGGA	22	12570
  BCL11A-10582	+	CAAGCCAAUGGCCAGUGCGGGGA	23	12571
  BCL11A-10583	+	ACAAGCCAAUGGCCAGUGCGGGGA	24	12572
  BCL11A-10584	+	GUCAGGAGUCUGGAUGGA	18	12573
  BCL11A-10585	+	CGUCAGGAGUCUGGAUGGA	19	12574
  BCL11A-10586	+	ACGUCAGGAGUCUGGAUGGA	20	12575
  BCL11A-10587	+	AACGUCAGGAGUCUGGAUGGA	21	12576
  BCL11A-10588	+	GAACGUCAGGAGUCUGGAUGGA	22	12577
  BCL11A-10589	+	UGAACGUCAGGAGUCUGGAUGGA	23	12578
  BCL11A-10590	+	UUGAACGUCAGGAGUCUGGAUGGA	24	12579
  BCL11A-10591	+	AGAGAGAGAAGAGAGAUA	18	12580
  BCL11A-10592	+	GAGAGAGAGAAGAGAGAUA	19	12581
  BCL11A-10593	+	AGAGAGAGAGAAGAGAGAUA	20	12582
  BCL11A-10594	+	GAGAGAGAGAGAAGAGAGAUA	21	12583
  BCL11A-10595	+	GGAGAGAGAGAGAAGAGAGAUA	22	12584
  BCL11A-10596	+	GGGAGAGAGAGAGAAGAGAGAUA	23	12585
  BCL11A-10597	+	AGGGAGAGAGAGAGAAGAGAGAUA	24	12586
  BCL11A-10598	+	GACAGAGACACACAAAAC	18	12587
  BCL11A-10599	+	GGACAGAGACACACAAAAC	19	12588
  BCL11A-10600	+	UGGACAGAGACACACAAAAC	20	12589
  BCL11A-10601	+	AUGGACAGAGACACACAAAAC	21	12590
  BCL11A-10602	+	GAUGGACAGAGACACACAAAAC	22	12591
  BCL11A-10603	+	GGAUGGACAGAGACACACAAAAC	23	12592
  BCL11A-10604	+	UGGAUGGACAGAGACACACAAAAC	24	12593
  BCL11A-10605	+	CGUGACGUCCCUGCGAAC	18	12594
  BCL11A-10606	+	ACGUGACGUCCCUGCGAAC	19	12595
  BCL11A-10607	+	GACGUGACGUCCCUGCGAAC	20	12596
  BCL11A-10608	+	GGACGUGACGUCCCUGCGAAC	21	12597
  BCL11A-10609	+	CGGACGUGACGUCCCUGCGAAC	22	12598
  BCL11A-10610	+	GCGGACGUGACGUCCCUGCGAAC	23	12599
  BCL11A-10611	+	UGCGGACGUGACGUCCCUGCGAAC	24	12600
  BCL11A-10612	+	CUGCUCCCCCCCACACAC	18	12601
  BCL11A-10613	+	CCUGCUCCCCCCCACACAC	19	12602
  BCL11A-10614	+	CCCUGCUCCCCCCCACACAC	20	12603
  BCL11A-10615	+	GCCCUGCUCCCCCCCACACAC	21	12604
  BCL11A-10616	+	CGCCCUGCUCCCCCCCACACAC	22	12605
  BCL11A-10617	+	GCGCCCUGCUCCCCCCCACACAC	23	12606
  BCL11A-10618	+	UGCGCCCUGCUCCCCCCCACACAC	24	12607
  BCL11A-10619	+	UGGACAUGAAAAAGAGAC	18	12608
  BCL11A-10620	+	CUGGACAUGAAAAAGAGAC	19	12609
  BCL11A-10621	+	GCUGGACAUGAAAAAGAGAC	20	12610
  BCL11A-10622	+	GGCUGGACAUGAAAAAGAGAC	21	12611
  BCL11A-10623	+	GGGCUGGACAUGAAAAAGAGAC	22	12612
  BCL11A-10624	+	GGGGCUGGACAUGAAAAAGAGAC	23	12613
  BCL11A-10625	+	AGGGGCUGGACAUGAAAAAGAGAC	24	12614
  BCL11A-10626	+	ACACAUCAGGGGCUGGAC	18	12615
  BCL11A-10627	+	CACACAUCAGGGGCUGGAC	19	12616
  BCL11A-10628	+	ACACACAUCAGGGGCUGGAC	20	12617
  BCL11A-10629	+	GACACACAUCAGGGGCUGGAC	21	12618
  BCL11A-10630	+	GGACACACAUCAGGGGCUGGAC	22	12619
  BCL11A-10631	+	UGGACACACAUCAGGGGCUGGAC	23	12620
  BCL11A-10632	+	AUGGACACACAUCAGGGGCUGGAC	24	12621
  BCL11A-6411	+	UAUUAUUGGGUUACUUAC	18	12622
  BCL11A-6412	+	CUAUUAUUGGGUUACUUAC	19	12623
  BCL11A-6413	+	ACUAUUAUUGGGUUACUUAC	20	12624
  BCL11A-6414	+	UACUAUUAUUGGGUUACUUAC	21	12625
  BCL11A-6415	+	UUACUAUUAUUGGGUUACUUAC	22	12626
  BCL11A-6416	+	AUUACUAUUAUUGGGUUACUUAC	23	12627
  BCL11A-6417	+	UAUUACUAUUAUUGGGUUACUUAC	24	12628
  BCL11A-10633	+	AAAAUGGCAAAAGCCCCC	18	12629
  BCL11A-10634	+	AAAAAUGGCAAAAGCCCCC	19	12630
  BCL11A-10635	+	AAAAAAUGGCAAAAGCCCCC	20	12631
  BCL11A-10636	+	AAAAAAAUGGCAAAAGCCCCC	21	12632
  BCL11A-10637	+	GAAAAAAAUGGCAAAAGCCCCC	22	12633
  BCL11A-10638	+	UGAAAAAAAUGGCAAAAGCCCCC	23	12634
  BCL11A-10639	+	AUGAAAAAAAUGGCAAAAGCCCCC	24	12635
  BCL11A-10640	+	ACGCCAGACGCGGCCCCC	18	12636
  BCL11A-10641	+	GACGCCAGACGCGGCCCCC	19	12637
  BCL11A-4456	+	GGACGCCAGACGCGGCCCCC	20	12638
  BCL11A-10642	+	CGGACGCCAGACGCGGCCCCC	21	12639
  BCL11A-10643	+	GCGGACGCCAGACGCGGCCCCC	22	12640
  BCL11A-10644	+	CGCGGACGCCAGACGCGGCCCCC	23	12641
  BCL11A-10645	+	CCGCGGACGCCAGACGCGGCCCCC	24	12642
  BCL11A-10646	+	GACGCCAGACGCGGCCCC	18	12643
  BCL11A-10647	+	GGACGCCAGACGCGGCCCC	19	12644
  BCL11A-4362	+	CGGACGCCAGACGCGGCCCC	20	12645
  BCL11A-10648	+	GCGGACGCCAGACGCGGCCCC	21	12646
  BCL11A-10649	+	CGCGGACGCCAGACGCGGCCCC	22	12647
  BCL11A-10650	+	CCGCGGACGCCAGACGCGGCCCC	23	12648
  BCL11A-10651	+	UCCGCGGACGCCAGACGCGGCCCC	24	12649
  BCL11A-10652	+	GGACGCCAGACGCGGCCC	18	12650
  BCL11A-10653	+	CGGACGCCAGACGCGGCCC	19	12651
  BCL11A-4825	+	GCGGACGCCAGACGCGGCCC	20	12652
  BCL11A-10654	+	CGCGGACGCCAGACGCGGCCC	21	12653
  BCL11A-10655	+	CCGCGGACGCCAGACGCGGCCC	22	12654
  BCL11A-10656	+	UCCGCGGACGCCAGACGCGGCCC	23	12655
  BCL11A-10657	+	CUCCGCGGACGCCAGACGCGGCCC	24	12656
  BCL11A-10658	+	CCGGGGGAGGGGCGGGCC	18	12657
  BCL11A-10659	+	CCCGGGGGAGGGGCGGGCC	19	12658
  BCL11A-5064	+	CCCCGGGGGAGGGGCGGGCC	20	12659
  BCL11A-10660	+	CCCCCGGGGGAGGGGCGGGCC	21	12660
  BCL11A-10661	+	GCCCCCGGGGGAGGGGCGGGCC	22	12661
  BCL11A-10662	+	GGCCCCCGGGGGAGGGGCGGGCC	23	12662
  BCL11A-10663	+	CGGCCCCCGGGGGAGGGGCGGGCC	24	12663
  BCL11A-10664	+	GGAGGGGGCGCUGGGGCC	18	12664
  BCL11A-10665	+	GGGAGGGGGCGCUGGGGCC	19	12665
  BCL11A-10666	+	GGGGAGGGGGCGCUGGGGCC	20	12666
  BCL11A-10667	+	AGGGGAGGGGGCGCUGGGGCC	21	12667
  BCL11A-10668	+	GAGGGGAGGGGGCGCUGGGGCC	22	12668
  BCL11A-10669	+	CGAGGGGAGGGGGCGCUGGGGCC	23	12669
  BCL11A-10670	+	CCGAGGGGAGGGGGCGCUGGGGCC	24	12670
  BCL11A-10671	+	CGCGGCGGUGGCGUGGCC	18	12671
  BCL11A-10672	+	CCGCGGCGGUGGCGUGGCC	19	12672
  BCL11A-9718	+	GCCGCGGCGGUGGCGUGGCC	20	12673
  BCL11A-10673	+	CGCCGCGGCGGUGGCGUGGCC	21	12674
  BCL11A-10674	+	GCGCCGCGGCGGUGGCGUGGCC	22	12675
  BCL11A-10675	+	AGCGCCGCGGCGGUGGCGUGGCC	23	12676
  BCL11A-10676	+	GAGCGCCGCGGCGGUGGCGUGGCC	24	12677
  BCL11A-10677	+	UGCGGGGCGGGGGGCUCC	18	12678
  BCL11A-10678	+	GUGCGGGGCGGGGGGCUCC	19	12679
  BCL11A-10679	+	GGUGCGGGGCGGGGGGCUCC	20	12680
  BCL11A-10680	+	AGGUGCGGGGCGGGGGGCUCC	21	12681
  BCL11A-10681	+	GAGGUGCGGGGCGGGGGGCUCC	22	12682
  BCL11A-10682	+	GGAGGUGCGGGGCGGGGGGCUCC	23	12683
  BCL11A-10683	+	GGGAGGUGCGGGGCGGGGGGCUCC	24	12684
  BCL11A-10684	+	AACAUGGGCAGGGCGAGC	18	12685
  BCL11A-10685	+	AAACAUGGGCAGGGCGAGC	19	12686
  BCL11A-9721	+	AAAACAUGGGCAGGGCGAGC	20	12687
  BCL11A-10686	+	CAAAACAUGGGCAGGGCGAGC	21	12688
  BCL11A-10687	+	ACAAAACAUGGGCAGGGCGAGC	22	12689
  BCL11A-10688	+	CACAAAACAUGGGCAGGGCGAGC	23	12690
  BCL11A-10689	+	ACACAAAACAUGGGCAGGGCGAGC	24	12691
  BCL11A-10690	+	GCCGAGGGGAGGGGGCGC	18	12692
  BCL11A-10691	+	GGCCGAGGGGAGGGGGCGC	19	12693
  BCL11A-4490	+	GGGCCGAGGGGAGGGGGCGC	20	12694
  BCL11A-10692	+	CGGGCCGAGGGGAGGGGGCGC	21	12695
  BCL11A-10693	+	GCGGGCCGAGGGGAGGGGGCGC	22	12696
  BCL11A-10694	+	GGCGGGCCGAGGGGAGGGGGCGC	23	12697
  BCL11A-10695	+	GGGCGGGCCGAGGGGAGGGGGCGC	24	12698
  BCL11A-10696	+	AUAAUACAAAGAUGGCGC	18	12699
  BCL11A-10697	+	AAUAAUACAAAGAUGGCGC	19	12700
  BCL11A-9565	+	AAAUAAUACAAAGAUGGCGC	20	12701
  BCL11A-10698	+	GAAAUAAUACAAAGAUGGCGC	21	12702
  BCL11A-10699	+	AGAAAUAAUACAAAGAUGGCGC	22	12703
  BCL11A-10700	+	UAGAAAUAAUACAAAGAUGGCGC	23	12704
  BCL11A-10701	+	UUAGAAAUAAUACAAAGAUGGCGC	24	12705
  BCL11A-10702	+	GAGGGGGAGGUGCGGGGC	18	12706
  BCL11A-10703	+	GGAGGGGGAGGUGCGGGGC	19	12707
  BCL11A-9724	+	GGGAGGGGGAGGUGCGGGGC	20	12708
  BCL11A-10704	+	GGGGAGGGGGAGGUGCGGGGC	21	12709
  BCL11A-10705	+	CGGGGAGGGGGAGGUGCGGGGC	22	12710
  BCL11A-10706	+	GCGGGGAGGGGGAGGUGCGGGGC	23	12711
  BCL11A-10707	+	UGCGGGGAGGGGGAGGUGCGGGGC	24	12712
  BCL11A-10708	+	CCGCGGCGGUGGCGUGGC	18	12713
  BCL11A-10709	+	GCCGCGGCGGUGGCGUGGC	19	12714
  BCL11A-9725	+	CGCCGCGGCGGUGGCGUGGC	20	12715
  BCL11A-10710	+	GCGCCGCGGCGGUGGCGUGGC	21	12716
  BCL11A-10711	+	AGCGCCGCGGCGGUGGCGUGGC	22	12717
  BCL11A-10712	+	GAGCGCCGCGGCGGUGGCGUGGC	23	12718
  BCL11A-10713	+	CGAGCGCCGCGGCGGUGGCGUGGC	24	12719
  BCL11A-10714	+	CAAGCCAAUGGCCAGUGC	18	12720
  BCL11A-10715	+	ACAAGCCAAUGGCCAGUGC	19	12721
  BCL11A-9727	+	GACAAGCCAAUGGCCAGUGC	20	12722
  BCL11A-10716	+	GGACAAGCCAAUGGCCAGUGC	21	12723
  BCL11A-10717	+	AGGACAAGCCAAUGGCCAGUGC	22	12724
  BCL11A-10718	+	CAGGACAAGCCAAUGGCCAGUGC	23	12725
  BCL11A-10719	+	CCAGGACAAGCCAAUGGCCAGUGC	24	12726
  BCL11A-10720	+	CACCAAUGGACACACAUC	18	12727
  BCL11A-10721	+	ACACCAAUGGACACACAUC	19	12728
  BCL11A-9729	+	CACACCAAUGGACACACAUC	20	12729
  BCL11A-10722	+	UCACACCAAUGGACACACAUC	21	12730
  BCL11A-10723	+	CUCACACCAAUGGACACACAUC	22	12731
  BCL11A-10724	+	GCUCACACCAAUGGACACACAUC	23	12732
  BCL11A-10725	+	AGCUCACACCAAUGGACACACAUC	24	12733
  BCL11A-10726	+	GACGGCUCGGUUCACAUC	18	12734
  BCL11A-10727	+	CGACGGCUCGGUUCACAUC	19	12735
  BCL11A-9568	+	ACGACGGCUCGGUUCACAUC	20	12736
  BCL11A-10728	+	GACGACGGCUCGGUUCACAUC	21	12737
  BCL11A-10729	+	GGACGACGGCUCGGUUCACAUC	22	12738
  BCL11A-10730	+	CGGACGACGGCUCGGUUCACAUC	23	12739
  BCL11A-10731	+	GCGGACGACGGCUCGGUUCACAUC	24	12740
  BCL11A-10732	+	UUAGAAAGAAGGAGACUC	18	12741
  BCL11A-10733	+	GUUAGAAAGAAGGAGACUC	19	12742
  BCL11A-10734	+	GGUUAGAAAGAAGGAGACUC	20	12743
  BCL11A-10735	+	GGGUUAGAAAGAAGGAGACUC	21	12744
  BCL11A-10736	+	CGGGUUAGAAAGAAGGAGACUC	22	12745
  BCL11A-10737	+	CCGGGUUAGAAAGAAGGAGACUC	23	12746
  BCL11A-10738	+	GCCGGGUUAGAAAGAAGGAGACUC	24	12747
  BCL11A-10739	+	UCUCUUUUACCUCGACUC	18	12748
  BCL11A-10740	+	AUCUCUUUUACCUCGACUC	19	12749
  BCL11A-10741	+	UAUCUCUUUUACCUCGACUC	20	12750
  BCL11A-10742	+	UUAUCUCUUUUACCUCGACUC	21	12751
  BCL11A-10743	+	UUUAUCUCUUUUACCUCGACUC	22	12752
  BCL11A-10744	+	CUUUAUCUCUUUUACCUCGACUC	23	12753
  BCL11A-10745	+	CCUUUAUCUCUUUUACCUCGACUC	24	12754
  BCL11A-10746	+	CUCUCGGAGGUUUUUCUC	18	12755
  BCL11A-10747	+	ACUCUCGGAGGUUUUUCUC	19	12756
  BCL11A-10748	+	GACUCUCGGAGGUUUUUCUC	20	12757
  BCL11A-10749	+	CGACUCUCGGAGGUUUUUCUC	21	12758
  BCL11A-10750	+	UCGACUCUCGGAGGUUUUUCUC	22	12759
  BCL11A-10751	+	CUCGACUCUCGGAGGUUUUUCUC	23	12760
  BCL11A-10752	+	CCUCGACUCUCGGAGGUUUUUCUC	24	12761
  BCL11A-10753	+	AAAAAAAAAAAAAAAAAG	18	12762
  BCL11A-10754	+	AAAAAAAAAAAAAAAAAAG	19	12763
  BCL11A-4526	+	AAAAAAAAAAAAAAAAAAAG	20	12764
  BCL11A-10755	+	AAAAAAAAAAAAAAAAAAAAG	21	12765
  BCL11A-10756	+	AAAAAAAAAAAAAAAAAAAAAG	22	12766
  BCL11A-10757	+	AAAAAAAAAAAAAAAAAAAAAAG	23	12767
  BCL11A-10758	+	AAAAAAAAAAAAAAAAAAAAAAAG	24	12768
  BCL11A-10759	+	GAGAGCCGGGUUAGAAAG	18	12769
  BCL11A-10760	+	GGAGAGCCGGGUUAGAAAG	19	12770
  BCL11A-10761	+	GGGAGAGCCGGGUUAGAAAG	20	12771
  BCL11A-10762	+	CGGGAGAGCCGGGUUAGAAAG	21	12772
  BCL11A-10763	+	UCGGGAGAGCCGGGUUAGAAAG	22	12773
  BCL11A-10764	+	AUCGGGAGAGCCGGGUUAGAAAG	23	12774
  BCL11A-10765	+	CAUCGGGAGAGCCGGGUUAGAAAG	24	12775
  BCL11A-10766	+	GGGCGAGCAGGAGAGAAG	18	12776
  BCL11A-10767	+	AGGGCGAGCAGGAGAGAAG	19	12777
  BCL11A-4629	+	CAGGGCGAGCAGGAGAGAAG	20	12778
  BCL11A-10768	+	GCAGGGCGAGCAGGAGAGAAG	21	12779
  BCL11A-10769	+	GGCAGGGCGAGCAGGAGAGAAG	22	12780
  BCL11A-10770	+	GGGCAGGGCGAGCAGGAGAGAAG	23	12781
  BCL11A-10771	+	UGGGCAGGGCGAGCAGGAGAGAAG	24	12782
  BCL11A-10772	+	AGAAGGGGAGGAGGGAAG	18	12783
  BCL11A-10773	+	GAGAAGGGGAGGAGGGAAG	19	12784
  BCL11A-4577	+	AGAGAAGGGGAGGAGGGAAG	20	12785
  BCL11A-10774	+	GAGAGAAGGGGAGGAGGGAAG	21	12786
  BCL11A-10775	+	GGAGAGAAGGGGAGGAGGGAAG	22	12787
  BCL11A-10776	+	AGGAGAGAAGGGGAGGAGGGAAG	23	12788
  BCL11A-10777	+	CAGGAGAGAAGGGGAGGAGGGAAG	24	12789
  BCL11A-10778	+	ACACGGCAAUGGUUCCAG	18	12790
  BCL11A-10779	+	UACACGGCAAUGGUUCCAG	19	12791
  BCL11A-10780	+	AUACACGGCAAUGGUUCCAG	20	12792
  BCL11A-10781	+	CAUACACGGCAAUGGUUCCAG	21	12793
  BCL11A-10782	+	GCAUACACGGCAAUGGUUCCAG	22	12794
  BCL11A-10783	+	UGCAUACACGGCAAUGGUUCCAG	23	12795
  BCL11A-10784	+	GUGCAUACACGGCAAUGGUUCCAG	24	12796
  BCL11A-10785	+	CAUGGGCAGGGCGAGCAG	18	12797
  BCL11A-10786	+	ACAUGGGCAGGGCGAGCAG	19	12798
  BCL11A-10787	+	AACAUGGGCAGGGCGAGCAG	20	12799
  BCL11A-10788	+	AAACAUGGGCAGGGCGAGCAG	21	12800
  BCL11A-10789	+	AAAACAUGGGCAGGGCGAGCAG	22	12801
  BCL11A-10790	+	CAAAACAUGGGCAGGGCGAGCAG	23	12802
  BCL11A-10791	+	ACAAAACAUGGGCAGGGCGAGCAG	24	12803
  BCL11A-10792	+	GGAGAGAGAGAGAGAGAG	18	12804
  BCL11A-10793	+	GGGAGAGAGAGAGAGAGAG	19	12805
  BCL11A-4999	+	AGGGAGAGAGAGAGAGAGAG	20	12806
  BCL11A-10794	+	GAGGGAGAGAGAGAGAGAGAG	21	12807
  BCL11A-10795	+	AGAGGGAGAGAGAGAGAGAGAG	22	12808
  BCL11A-10796	+	UAGAGGGAGAGAGAGAGAGAGAG	23	12809
  BCL11A-10797	+	AUAGAGGGAGAGAGAGAGAGAGAG	24	12810
  BCL11A-10798	+	AAAGAGGGAGAGAGAGAG	18	12811
  BCL11A-10799	+	AAAAGAGGGAGAGAGAGAG	19	12812
  BCL11A-4916	+	AAAAAGAGGGAGAGAGAGAG	20	12813
  BCL11A-10800	+	AAAAAAGAGGGAGAGAGAGAG	21	12814
  BCL11A-10801	+	AAAAAAAGAGGGAGAGAGAGAG	22	12815
  BCL11A-10802	+	AAAAAAAAGAGGGAGAGAGAGAG	23	12816
  BCL11A-10803	+	AAAAAAAAAGAGGGAGAGAGAGAG	24	12817
  BCL11A-10804	+	GCAGGGCGAGCAGGAGAG	18	12818
  BCL11A-10805	+	GGCAGGGCGAGCAGGAGAG	19	12819
  BCL11A-4870	+	GGGCAGGGCGAGCAGGAGAG	20	12820
  BCL11A-10806	+	UGGGCAGGGCGAGCAGGAGAG	21	12821
  BCL11A-10807	+	AUGGGCAGGGCGAGCAGGAGAG	22	12822
  BCL11A-10808	+	CAUGGGCAGGGCGAGCAGGAGAG	23	12823
  BCL11A-10809	+	ACAUGGGCAGGGCGAGCAGGAGAG	24	12824
  BCL11A-10810	+	GUGGCGUGGCCGGGAGAG	18	12825
  BCL11A-10811	+	GGUGGCGUGGCCGGGAGAG	19	12826
  BCL11A-10812	+	CGGUGGCGUGGCCGGGAGAG	20	12827
  BCL11A-10813	+	GCGGUGGCGUGGCCGGGAGAG	21	12828
  BCL11A-10814	+	GGCGGUGGCGUGGCCGGGAGAG	22	12829
  BCL11A-10815	+	CGGCGGUGGCGUGGCCGGGAGAG	23	12830
  BCL11A-10816	+	GCGGCGGUGGCGUGGCCGGGAGAG	24	12831
  BCL11A-10817	+	GGGGAGGGGCGGGCCGAG	18	12832
  BCL11A-10818	+	GGGGGAGGGGCGGGCCGAG	19	12833
  BCL11A-4677	+	CGGGGGAGGGGCGGGCCGAG	20	12834
  BCL11A-10819	+	CCGGGGGAGGGGCGGGCCGAG	21	12835
  BCL11A-10820	+	CCCGGGGGAGGGGCGGGCCGAG	22	12836
  BCL11A-10821	+	CCCCGGGGGAGGGGCGGGCCGAG	23	12837
  BCL11A-10822	+	CCCCCGGGGGAGGGGCGGGCCGAG	24	12838
  BCL11A-10823	+	AAACAUGGGCAGGGCGAG	18	12839
  BCL11A-10824	+	AAAACAUGGGCAGGGCGAG	19	12840
  BCL11A-10825	+	CAAAACAUGGGCAGGGCGAG	20	12841
  BCL11A-10826	+	ACAAAACAUGGGCAGGGCGAG	21	12842
  BCL11A-10827	+	CACAAAACAUGGGCAGGGCGAG	22	12843
  BCL11A-10828	+	ACACAAAACAUGGGCAGGGCGAG	23	12844
  BCL11A-10829	+	CACACAAAACAUGGGCAGGGCGAG	24	12845
  BCL11A-10830	+	AGCAGGAGAGAAGGGGAG	18	12846
  BCL11A-10831	+	GAGCAGGAGAGAAGGGGAG	19	12847
  BCL11A-5082	+	CGAGCAGGAGAGAAGGGGAG	20	12848
  BCL11A-10832	+	GCGAGCAGGAGAGAAGGGGAG	21	12849
  BCL11A-10833	+	GGCGAGCAGGAGAGAAGGGGAG	22	12850
  BCL11A-10834	+	GGGCGAGCAGGAGAGAAGGGGAG	23	12851
  BCL11A-10835	+	AGGGCGAGCAGGAGAGAAGGGGAG	24	12852
  BCL11A-10836	+	AAUGGCCAGUGCGGGGAG	18	12853
  BCL11A-10837	+	CAAUGGCCAGUGCGGGGAG	19	12854
  BCL11A-9572	+	CCAAUGGCCAGUGCGGGGAG	20	12855
  BCL11A-10838	+	GCCAAUGGCCAGUGCGGGGAG	21	12856
  BCL11A-10839	+	AGCCAAUGGCCAGUGCGGGGAG	22	12857
  BCL11A-10840	+	AAGCCAAUGGCCAGUGCGGGGAG	23	12858
  BCL11A-10841	+	CAAGCCAAUGGCCAGUGCGGGGAG	24	12859
  BCL11A-10842	+	GAGAGAGAAGAGAGAUAG	18	12860
  BCL11A-10843	+	AGAGAGAGAAGAGAGAUAG	19	12861
  BCL11A-9740	+	GAGAGAGAGAAGAGAGAUAG	20	12862
  BCL11A-10844	+	AGAGAGAGAGAAGAGAGAUAG	21	12863
  BCL11A-10845	+	GAGAGAGAGAGAAGAGAGAUAG	22	12864
  BCL11A-10846	+	GGAGAGAGAGAGAAGAGAGAUAG	23	12865
  BCL11A-10847	+	GGGAGAGAGAGAGAAGAGAGAUAG	24	12866
  BCL11A-10848	+	CGCCAGACGCGGCCCCCG	18	12867
  BCL11A-10849	+	ACGCCAGACGCGGCCCCCG	19	12868
  BCL11A-4351	+	GACGCCAGACGCGGCCCCCG	20	12869
  BCL11A-10850	+	GGACGCCAGACGCGGCCCCCG	21	12870
  BCL11A-10851	+	CGGACGCCAGACGCGGCCCCCG	22	12871
  BCL11A-10852	+	GCGGACGCCAGACGCGGCCCCCG	23	12872
  BCL11A-10853	+	CGCGGACGCCAGACGCGGCCCCCG	24	12873
  BCL11A-10854	+	CGGGGGAGGGGCGGGCCG	18	12874
  BCL11A-10855	+	CCGGGGGAGGGGCGGGCCG	19	12875
  BCL11A-4642	+	CCCGGGGGAGGGGCGGGCCG	20	12876
  BCL11A-10856	+	CCCCGGGGGAGGGGCGGGCCG	21	12877
  BCL11A-10857	+	CCCCCGGGGGAGGGGCGGGCCG	22	12878
  BCL11A-10858	+	GCCCCCGGGGGAGGGGCGGGCCG	23	12879
  BCL11A-10859	+	GGCCCCCGGGGGAGGGGCGGGCCG	24	12880
  BCL11A-10860	+	GCGGCGGCGGCGGCGGCG	18	12881
  BCL11A-10861	+	GGCGGCGGCGGCGGCGGCG	19	12882
  BCL11A-5097	+	CGGCGGCGGCGGCGGCGGCG	20	12883
  BCL11A-10862	+	GCGGCGGCGGCGGCGGCGGCG	21	12884
  BCL11A-10863	+	GGCGGCGGCGGCGGCGGCGGCG	22	12885
  BCL11A-10864	+	CGGCGGCGGCGGCGGCGGCGGCG	23	12886
  BCL11A-10865	+	GCGGCGGCGGCGGCGGCGGCGGCG	24	12887
  BCL11A-10866	+	AGGGGGAGGUGCGGGGCG	18	12888
  BCL11A-10867	+	GAGGGGGAGGUGCGGGGCG	19	12889
  BCL11A-9749	+	GGAGGGGGAGGUGCGGGGCG	20	12890
  BCL11A-10868	+	GGGAGGGGGAGGUGCGGGGCG	21	12891
  BCL11A-10869	+	GGGGAGGGGGAGGUGCGGGGCG	22	12892
  BCL11A-10870	+	CGGGGAGGGGGAGGUGCGGGGCG	23	12893
  BCL11A-10871	+	GCGGGGAGGGGGAGGUGCGGGGCG	24	12894
  BCL11A-10872	+	GGCCGAGGGGAGGGGGCG	18	12895
  BCL11A-10873	+	GGGCCGAGGGGAGGGGGCG	19	12896
  BCL11A-5099	+	CGGGCCGAGGGGAGGGGGCG	20	12897
  BCL11A-10874	+	GCGGGCCGAGGGGAGGGGGCG	21	12898
  BCL11A-10875	+	GGCGGGCCGAGGGGAGGGGGCG	22	12899
  BCL11A-10876	+	GGGCGGGCCGAGGGGAGGGGGCG	23	12900
  BCL11A-10877	+	GGGGCGGGCCGAGGGGAGGGGGCG	24	12901
  BCL11A-10878	+	AAUAAUACAAAGAUGGCG	18	12902
  BCL11A-10879	+	AAAUAAUACAAAGAUGGCG	19	12903
  BCL11A-10880	+	GAAAUAAUACAAAGAUGGCG	20	12904
  BCL11A-10881	+	AGAAAUAAUACAAAGAUGGCG	21	12905
  BCL11A-10882	+	UAGAAAUAAUACAAAGAUGGCG	22	12906
  BCL11A-10883	+	UUAGAAAUAAUACAAAGAUGGCG	23	12907
  BCL11A-10884	+	AUUAGAAAUAAUACAAAGAUGGCG	24	12908
  BCL11A-10885	+	AAGCCAAUGGCCAGUGCG	18	12909
  BCL11A-10886	+	CAAGCCAAUGGCCAGUGCG	19	12910
  BCL11A-9751	+	ACAAGCCAAUGGCCAGUGCG	20	12911
  BCL11A-10887	+	GACAAGCCAAUGGCCAGUGCG	21	12912
  BCL11A-10888	+	GGACAAGCCAAUGGCCAGUGCG	22	12913
  BCL11A-10889	+	AGGACAAGCCAAUGGCCAGUGCG	23	12914
  BCL11A-10890	+	CAGGACAAGCCAAUGGCCAGUGCG	24	12915
  BCL11A-6490	+	GGGUUUGCCUUGCUUGCG	18	12916
  BCL11A-6491	+	GGGGUUUGCCUUGCUUGCG	19	12917
  BCL11A-6492	+	UGGGGUUUGCCUUGCUUGCG	20	12918
  BCL11A-6493	+	CUGGGGUUUGCCUUGCUUGCG	21	12919
  BCL11A-6494	+	GCUGGGGUUUGCCUUGCUUGCG	22	12920
  BCL11A-6495	+	UGCUGGGGUUUGCCUUGCUUGCG	23	12921
  BCL11A-6496	+	GUGCUGGGGUUUGCCUUGCUUGCG	24	12922
  BCL11A-10891	+	CAGGGGUGGGAGGAAAGG	18	12923
  BCL11A-10892	+	GCAGGGGUGGGAGGAAAGG	19	12924
  BCL11A-10893	+	GGCAGGGGUGGGAGGAAAGG	20	12925
  BCL11A-10894	+	UGGCAGGGGUGGGAGGAAAGG	21	12926
  BCL11A-10895	+	GUGGCAGGGGUGGGAGGAAAGG	22	12927
  BCL11A-10896	+	GGUGGCAGGGGUGGGAGGAAAGG	23	12928
  BCL11A-10897	+	GGGUGGCAGGGGUGGGAGGAAAGG	24	12929
  BCL11A-10898	+	ACACAAAACAUGGGCAGG	18	12930
  BCL11A-10899	+	CACACAAAACAUGGGCAGG	19	12931
  BCL11A-10900	+	ACACACAAAACAUGGGCAGG	20	12932
  BCL11A-10901	+	GACACACAAAACAUGGGCAGG	21	12933
  BCL11A-10902	+	AGACACACAAAACAUGGGCAGG	22	12934
  BCL11A-10903	+	GAGACACACAAAACAUGGGCAGG	23	12935
  BCL11A-10904	+	AGAGACACACAAAACAUGGGCAGG	24	12936
  BCL11A-10905	+	AAAAAAAAAAAAAAGAGG	18	12937
  BCL11A-10906	+	AAAAAAAAAAAAAAAGAGG	19	12938
  BCL11A-4903	+	AAAAAAAAAAAAAAAAGAGG	20	12939
  BCL11A-10907	+	AAAAAAAAAAAAAAAAAGAGG	21	12940
  BCL11A-10908	+	AAAAAAAAAAAAAAAAAAGAGG	22	12941
  BCL11A-10909	+	AAAAAAAAAAAAAAAAAAAGAGG	23	12942
  BCL11A-10910	+	AAAAAAAAAAAAAAAAAAAAGAGG	24	12943
  BCL11A-10911	+	AGAGAAGAGAGAUAGAGG	18	12944
  BCL11A-10912	+	GAGAGAAGAGAGAUAGAGG	19	12945
  BCL11A-10913	+	AGAGAGAAGAGAGAUAGAGG	20	12946
  BCL11A-10914	+	GAGAGAGAAGAGAGAUAGAGG	21	12947
  BCL11A-10915	+	AGAGAGAGAAGAGAGAUAGAGG	22	12948
  BCL11A-10916	+	GAGAGAGAGAAGAGAGAUAGAGG	23	12949
  BCL11A-10917	+	AGAGAGAGAGAAGAGAGAUAGAGG	24	12950
  BCL11A-10918	+	GCAGGAGAGAAGGGGAGG	18	12951
  BCL11A-10919	+	AGCAGGAGAGAAGGGGAGG	19	12952
  BCL11A-4408	+	GAGCAGGAGAGAAGGGGAGG	20	12953
  BCL11A-10920	+	CGAGCAGGAGAGAAGGGGAGG	21	12954
  BCL11A-10921	+	GCGAGCAGGAGAGAAGGGGAGG	22	12955
  BCL11A-10922	+	GGCGAGCAGGAGAGAAGGGGAGG	23	12956
  BCL11A-10923	+	GGGCGAGCAGGAGAGAAGGGGAGG	24	12957
  BCL11A-10924	+	AUGGCCAGUGCGGGGAGG	18	12958
  BCL11A-10925	+	AAUGGCCAGUGCGGGGAGG	19	12959
  BCL11A-9756	+	CAAUGGCCAGUGCGGGGAGG	20	12960
  BCL11A-10926	+	CCAAUGGCCAGUGCGGGGAGG	21	12961
  BCL11A-10927	+	GCCAAUGGCCAGUGCGGGGAGG	22	12962
  BCL11A-10928	+	AGCCAAUGGCCAGUGCGGGGAGG	23	12963
  BCL11A-10929	+	AAGCCAAUGGCCAGUGCGGGGAGG	24	12964
  BCL11A-10930	+	GCCAGACGCGGCCCCCGG	18	12965
  BCL11A-10931	+	CGCCAGACGCGGCCCCCGG	19	12966
  BCL11A-4561	+	ACGCCAGACGCGGCCCCCGG	20	12967
  BCL11A-10932	+	GACGCCAGACGCGGCCCCCGG	21	12968
  BCL11A-10933	+	GGACGCCAGACGCGGCCCCCGG	22	12969
  BCL11A-10934	+	CGGACGCCAGACGCGGCCCCCGG	23	12970
  BCL11A-10935	+	GCGGACGCCAGACGCGGCCCCCGG	24	12971
  BCL11A-10936	+	CGGCGGUGGCGUGGCCGG	18	12972
  BCL11A-10937	+	GCGGCGGUGGCGUGGCCGG	19	12973
  BCL11A-10938	+	CGCGGCGGUGGCGUGGCCGG	20	12974
  BCL11A-10939	+	CCGCGGCGGUGGCGUGGCCGG	21	12975
  BCL11A-10940	+	GCCGCGGCGGUGGCGUGGCCGG	22	12976
  BCL11A-10941	+	CGCCGCGGCGGUGGCGUGGCCGG	23	12977
  BCL11A-10942	+	GCGCCGCGGCGGUGGCGUGGCCGG	24	12978
  BCL11A-10943	+	CGGCGGCGGCGGCGGCGG	18	12979
  BCL11A-10944	+	GCGGCGGCGGCGGCGGCGG	19	12980
  BCL11A-4479	+	GGCGGCGGCGGCGGCGGCGG	20	12981
  BCL11A-10945	+	CGGCGGCGGCGGCGGCGGCGG	21	12982
  BCL11A-10946	+	GCGGCGGCGGCGGCGGCGGCGG	22	12983
  BCL11A-10947	+	GGCGGCGGCGGCGGCGGCGGCGG	23	12984
  BCL11A-10948	+	CGGCGGCGGCGGCGGCGGCGGCGG	24	12985
  BCL11A-10949	+	CGGCUCGGUUCACAUCGG	18	12986
  BCL11A-10950	+	ACGGCUCGGUUCACAUCGG	19	12987
  BCL11A-10951	+	GACGGCUCGGUUCACAUCGG	20	12988
  BCL11A-10952	+	CGACGGCUCGGUUCACAUCGG	21	12989
  BCL11A-10953	+	ACGACGGCUCGGUUCACAUCGG	22	12990
  BCL11A-10954	+	GACGACGGCUCGGUUCACAUCGG	23	12991
  BCL11A-10955	+	GGACGACGGCUCGGUUCACAUCGG	24	12992
  BCL11A-10956	+	AGGGGUGGGAGGAAAGGG	18	12993
  BCL11A-10957	+	CAGGGGUGGGAGGAAAGGG	19	12994
  BCL11A-9759	+	GCAGGGGUGGGAGGAAAGGG	20	12995
  BCL11A-10958	+	GGCAGGGGUGGGAGGAAAGGG	21	12996
  BCL11A-10959	+	UGGCAGGGGUGGGAGGAAAGGG	22	12997
  BCL11A-10960	+	GUGGCAGGGGUGGGAGGAAAGGG	23	12998
  BCL11A-10961	+	GGUGGCAGGGGUGGGAGGAAAGGG	24	12999
  BCL11A-10962	+	GCGAGCAGGAGAGAAGGG	18	13000
  BCL11A-10963	+	GGCGAGCAGGAGAGAAGGG	19	13001
  BCL11A-4873	+	GGGCGAGCAGGAGAGAAGGG	20	13002
  BCL11A-10964	+	AGGGCGAGCAGGAGAGAAGGG	21	13003
  BCL11A-10965	+	CAGGGCGAGCAGGAGAGAAGGG	22	13004
  BCL11A-10966	+	GCAGGGCGAGCAGGAGAGAAGGG	23	13005
  BCL11A-10967	+	GGCAGGGCGAGCAGGAGAGAAGGG	24	13006
  BCL11A-10968	+	AAGAAAGGGGUGGCAGGG	18	13007
  BCL11A-10969	+	GAAGAAAGGGGUGGCAGGG	19	13008
  BCL11A-10970	+	AGAAGAAAGGGGUGGCAGGG	20	13009
  BCL11A-10971	+	GAGAAGAAAGGGGUGGCAGGG	21	13010
  BCL11A-10972	+	AGAGAAGAAAGGGGUGGCAGGG	22	13011
  BCL11A-10973	+	GAGAGAAGAAAGGGGUGGCAGGG	23	13012
  BCL11A-10974	+	GGAGAGAAGAAAGGGGUGGCAGGG	24	13013
  BCL11A-10975	+	GGAGGGGCGGGCCGAGGG	18	13014
  BCL11A-10976	+	GGGAGGGGCGGGCCGAGGG	19	13015
  BCL11A-4875	+	GGGGAGGGGCGGGCCGAGGG	20	13016
  BCL11A-10977	+	GGGGGAGGGGCGGGCCGAGGG	21	13017
  BCL11A-10978	+	CGGGGGAGGGGCGGGCCGAGGG	22	13018
  BCL11A-10979	+	CCGGGGGAGGGGCGGGCCGAGGG	23	13019
  BCL11A-10980	+	CCCGGGGGAGGGGCGGGCCGAGGG	24	13020
  BCL11A-10981	+	GAGAGAAGGGGAGGAGGG	18	13021
  BCL11A-10982	+	GGAGAGAAGGGGAGGAGGG	19	13022
  BCL11A-4998	+	AGGAGAGAAGGGGAGGAGGG	20	13023
  BCL11A-10983	+	CAGGAGAGAAGGGGAGGAGGG	21	13024
  BCL11A-10984	+	GCAGGAGAGAAGGGGAGGAGGG	22	13025
  BCL11A-10985	+	AGCAGGAGAGAAGGGGAGGAGGG	23	13026
  BCL11A-10986	+	GAGCAGGAGAGAAGGGGAGGAGGG	24	13027
  BCL11A-10987	+	GCGGCCCCCGGGGGAGGG	18	13028
  BCL11A-10988	+	CGCGGCCCCCGGGGGAGGG	19	13029
  BCL11A-4959	+	ACGCGGCCCCCGGGGGAGGG	20	13030
  BCL11A-10989	+	GACGCGGCCCCCGGGGGAGGG	21	13031
  BCL11A-10990	+	AGACGCGGCCCCCGGGGGAGGG	22	13032
  BCL11A-10991	+	CAGACGCGGCCCCCGGGGGAGGG	23	13033
  BCL11A-10992	+	CCAGACGCGGCCCCCGGGGGAGGG	24	13034
  BCL11A-10993	+	CCCCGGGGGAGGGGCGGG	18	13035
  BCL11A-10994	+	CCCCCGGGGGAGGGGCGGG	19	13036
  BCL11A-4817	+	GCCCCCGGGGGAGGGGCGGG	20	13037
  BCL11A-10995	+	GGCCCCCGGGGGAGGGGCGGG	21	13038
  BCL11A-10996	+	CGGCCCCCGGGGGAGGGGCGGG	22	13039
  BCL11A-10997	+	GCGGCCCCCGGGGGAGGGGCGGG	23	13040
  BCL11A-10998	+	CGCGGCCCCCGGGGGAGGGGCGGG	24	13041
  BCL11A-6504	+	GACAUGGUGGGCUGCGGG	18	13042
  BCL11A-6505	+	AGACAUGGUGGGCUGCGGG	19	13043
  BCL11A-6506	+	GAGACAUGGUGGGCUGCGGG	20	13044
  BCL11A-6507	+	CGAGACAUGGUGGGCUGCGGG	21	13045
  BCL11A-6508	+	GCGAGACAUGGUGGGCUGCGGG	22	13046
  BCL11A-6509	+	GGCGAGACAUGGUGGGCUGCGGG	23	13047
  BCL11A-6510	+	CGGCGAGACAUGGUGGGCUGCGGG	24	13048
  BCL11A-10999	+	GCCAAUGGCCAGUGCGGG	18	13049
  BCL11A-11000	+	AGCCAAUGGCCAGUGCGGG	19	13050
  BCL11A-11001	+	AAGCCAAUGGCCAGUGCGGG	20	13051
  BCL11A-11002	+	CAAGCCAAUGGCCAGUGCGGG	21	13052
  BCL11A-11003	+	ACAAGCCAAUGGCCAGUGCGGG	22	13053
  BCL11A-11004	+	GACAAGCCAAUGGCCAGUGCGGG	23	13054
  BCL11A-11005	+	GGACAAGCCAAUGGCCAGUGCGGG	24	13055
  BCL11A-11006	+	GGGAGGGGGAGGUGCGGG	18	13056
  BCL11A-11007	+	GGGGAGGGGGAGGUGCGGG	19	13057
  BCL11A-11008	+	CGGGGAGGGGGAGGUGCGGG	20	13058
  BCL11A-11009	+	GCGGGGAGGGGGAGGUGCGGG	21	13059
  BCL11A-11010	+	UGCGGGGAGGGGGAGGUGCGGG	22	13060
  BCL11A-11011	+	GUGCGGGGAGGGGGAGGUGCGGG	23	13061
  BCL11A-11012	+	AGUGCGGGGAGGGGGAGGUGCGGG	24	13062
  BCL11A-11013	+	CGAGCAGGAGAGAAGGGG	18	13063
  BCL11A-11014	+	GCGAGCAGGAGAGAAGGGG	19	13064
  BCL11A-4476	+	GGCGAGCAGGAGAGAAGGGG	20	13065
  BCL11A-11015	+	GGGCGAGCAGGAGAGAAGGGG	21	13066
  BCL11A-11016	+	AGGGCGAGCAGGAGAGAAGGGG	22	13067
  BCL11A-11017	+	CAGGGCGAGCAGGAGAGAAGGGG	23	13068
  BCL11A-11018	+	GCAGGGCGAGCAGGAGAGAAGGGG	24	13069
  BCL11A-11019	+	AGAAAGGGGUGGCAGGGG	18	13070
  BCL11A-11020	+	AAGAAAGGGGUGGCAGGGG	19	13071
  BCL11A-9762	+	GAAGAAAGGGGUGGCAGGGG	20	13072
  BCL11A-11021	+	AGAAGAAAGGGGUGGCAGGGG	21	13073
  BCL11A-11022	+	GAGAAGAAAGGGGUGGCAGGGG	22	13074
  BCL11A-11023	+	AGAGAAGAAAGGGGUGGCAGGGG	23	13075
  BCL11A-11024	+	GAGAGAAGAAAGGGGUGGCAGGGG	24	13076
  BCL11A-11025	+	AUGGACACACAUCAGGGG	18	13077
  BCL11A-11026	+	AAUGGACACACAUCAGGGG	19	13078
  BCL11A-11027	+	CAAUGGACACACAUCAGGGG	20	13079
  BCL11A-11028	+	CCAAUGGACACACAUCAGGGG	21	13080
  BCL11A-11029	+	ACCAAUGGACACACAUCAGGGG	22	13081
  BCL11A-11030	+	CACCAAUGGACACACAUCAGGGG	23	13082
  BCL11A-11031	+	ACACCAAUGGACACACAUCAGGGG	24	13083
  BCL11A-11032	+	GAGGGGCGGGCCGAGGGG	18	13084
  BCL11A-11033	+	GGAGGGGCGGGCCGAGGGG	19	13085
  BCL11A-4486	+	GGGAGGGGCGGGCCGAGGGG	20	13086
  BCL11A-11034	+	GGGGAGGGGCGGGCCGAGGGG	21	13087
  BCL11A-11035	+	GGGGGAGGGGCGGGCCGAGGGG	22	13088
  BCL11A-11036	+	CGGGGGAGGGGCGGGCCGAGGGG	23	13089
  BCL11A-11037	+	CCGGGGGAGGGGCGGGCCGAGGGG	24	13090
  BCL11A-11038	+	CAGACGCGGCCCCCGGGG	18	13091
  BCL11A-11039	+	CCAGACGCGGCCCCCGGGG	19	13092
  BCL11A-4816	+	GCCAGACGCGGCCCCCGGGG	20	13093
  BCL11A-11040	+	CGCCAGACGCGGCCCCCGGGG	21	13094
  BCL11A-11041	+	ACGCCAGACGCGGCCCCCGGGG	22	13095
  BCL11A-11042	+	GACGCCAGACGCGGCCCCCGGGG	23	13096
  BCL11A-11043	+	GGACGCCAGACGCGGCCCCCGGGG	24	13097
  BCL11A-11044	+	CCAAUGGCCAGUGCGGGG	18	13098
  BCL11A-11045	+	GCCAAUGGCCAGUGCGGGG	19	13099
  BCL11A-9763	+	AGCCAAUGGCCAGUGCGGGG	20	13100
  BCL11A-11046	+	AAGCCAAUGGCCAGUGCGGGG	21	13101
  BCL11A-11047	+	CAAGCCAAUGGCCAGUGCGGGG	22	13102
  BCL11A-11048	+	ACAAGCCAAUGGCCAGUGCGGGG	23	13103
  BCL11A-11049	+	GACAAGCCAAUGGCCAGUGCGGGG	24	13104
  BCL11A-11050	+	GGAGGGGGAGGUGCGGGG	18	13105
  BCL11A-11051	+	GGGAGGGGGAGGUGCGGGG	19	13106
  BCL11A-9764	+	GGGGAGGGGGAGGUGCGGGG	20	13107
  BCL11A-11052	+	CGGGGAGGGGGAGGUGCGGGG	21	13108
  BCL11A-11053	+	GCGGGGAGGGGGAGGUGCGGGG	22	13109
  BCL11A-11054	+	UGCGGGGAGGGGGAGGUGCGGGG	23	13110
  BCL11A-11055	+	GUGCGGGGAGGGGGAGGUGCGGGG	24	13111
  BCL11A-11056	+	AGACGCGGCCCCCGGGGG	18	13112
  BCL11A-11057	+	CAGACGCGGCCCCCGGGGG	19	13113
  BCL11A-4635	+	CCAGACGCGGCCCCCGGGGG	20	13114
  BCL11A-11058	+	GCCAGACGCGGCCCCCGGGGG	21	13115
  BCL11A-11059	+	CGCCAGACGCGGCCCCCGGGGG	22	13116
  BCL11A-11060	+	ACGCCAGACGCGGCCCCCGGGGG	23	13117
  BCL11A-11061	+	GACGCCAGACGCGGCCCCCGGGGG	24	13118
  BCL11A-11062	+	UGGGAGGAAAGGGUGGGG	18	13119
  BCL11A-11063	+	GUGGGAGGAAAGGGUGGGG	19	13120
  BCL11A-9766	+	GGUGGGAGGAAAGGGUGGGG	20	13121
  BCL11A-11064	+	GGGUGGGAGGAAAGGGUGGGG	21	13122
  BCL11A-11065	+	GGGGUGGGAGGAAAGGGUGGGG	22	13123
  BCL11A-11066	+	AGGGGUGGGAGGAAAGGGUGGGG	23	13124
  BCL11A-11067	+	CAGGGGUGGGAGGAAAGGGUGGGG	24	13125
  BCL11A-11068	+	AGACACACAAAACAUGGG	18	13126
  BCL11A-11069	+	GAGACACACAAAACAUGGG	19	13127
  BCL11A-11070	+	AGAGACACACAAAACAUGGG	20	13128
  BCL11A-11071	+	CAGAGACACACAAAACAUGGG	21	13129
  BCL11A-11072	+	ACAGAGACACACAAAACAUGGG	22	13130
  BCL11A-11073	+	GACAGAGACACACAAAACAUGGG	23	13131
  BCL11A-11074	+	GGACAGAGACACACAAAACAUGGG	24	13132
  BCL11A-11075	+	GCAAUGGUUCCAGAUGGG	18	13133
  BCL11A-11076	+	GGCAAUGGUUCCAGAUGGG	19	13134
  BCL11A-11077	+	CGGCAAUGGUUCCAGAUGGG	20	13135
  BCL11A-11078	+	ACGGCAAUGGUUCCAGAUGGG	21	13136
  BCL11A-11079	+	CACGGCAAUGGUUCCAGAUGGG	22	13137
  BCL11A-11080	+	ACACGGCAAUGGUUCCAGAUGGG	23	13138
  BCL11A-11081	+	UACACGGCAAUGGUUCCAGAUGGG	24	13139
  BCL11A-11082	+	GUGGGAGGAAAGGGUGGG	18	13140
  BCL11A-11083	+	GGUGGGAGGAAAGGGUGGG	19	13141
  BCL11A-9767	+	GGGUGGGAGGAAAGGGUGGG	20	13142
  BCL11A-11084	+	GGGGUGGGAGGAAAGGGUGGG	21	13143
  BCL11A-11085	+	AGGGGUGGGAGGAAAGGGUGGG	22	13144
  BCL11A-11086	+	CAGGGGUGGGAGGAAAGGGUGGG	23	13145
  BCL11A-11087	+	GCAGGGGUGGGAGGAAAGGGUGGG	24	13146
  BCL11A-11088	+	AGGGGUGGCAGGGGUGGG	18	13147
  BCL11A-11089	+	AAGGGGUGGCAGGGGUGGG	19	13148
  BCL11A-9768	+	AAAGGGGUGGCAGGGGUGGG	20	13149
  BCL11A-11090	+	GAAAGGGGUGGCAGGGGUGGG	21	13150
  BCL11A-11091	+	AGAAAGGGGUGGCAGGGGUGGG	22	13151
  BCL11A-11092	+	AAGAAAGGGGUGGCAGGGGUGGG	23	13152
  BCL11A-11093	+	GAAGAAAGGGGUGGCAGGGGUGGG	24	13153
  BCL11A-11094	+	UGAACGUCAGGAGUCUGG	18	13154
  BCL11A-11095	+	UUGAACGUCAGGAGUCUGG	19	13155
  BCL11A-11096	+	CUUGAACGUCAGGAGUCUGG	20	13156
  BCL11A-11097	+	ACUUGAACGUCAGGAGUCUGG	21	13157
  BCL11A-11098	+	AACUUGAACGUCAGGAGUCUGG	22	13158
  BCL11A-11099	+	GAACUUGAACGUCAGGAGUCUGG	23	13159
  BCL11A-11100	+	CGAACUUGAACGUCAGGAGUCUGG	24	13160
  BCL11A-11101	+	GCCGCGGCGGUGGCGUGG	18	13161
  BCL11A-11102	+	CGCCGCGGCGGUGGCGUGG	19	13162
  BCL11A-11103	+	GCGCCGCGGCGGUGGCGUGG	20	13163
  BCL11A-11104	+	AGCGCCGCGGCGGUGGCGUGG	21	13164
  BCL11A-11105	+	GAGCGCCGCGGCGGUGGCGUGG	22	13165
  BCL11A-11106	+	CGAGCGCCGCGGCGGUGGCGUGG	23	13166
  BCL11A-11107	+	GCGAGCGCCGCGGCGGUGGCGUGG	24	13167
  BCL11A-11108	+	GGUGGGAGGAAAGGGUGG	18	13168
  BCL11A-11109	+	GGGUGGGAGGAAAGGGUGG	19	13169
  BCL11A-9770	+	GGGGUGGGAGGAAAGGGUGG	20	13170
  BCL11A-11110	+	AGGGGUGGGAGGAAAGGGUGG	21	13171
  BCL11A-11111	+	CAGGGGUGGGAGGAAAGGGUGG	22	13172
  BCL11A-11112	+	GCAGGGGUGGGAGGAAAGGGUGG	23	13173
  BCL11A-11113	+	GGCAGGGGUGGGAGGAAAGGGUGG	24	13174
  BCL11A-11114	+	GAGAGAAGAAAGGGGUGG	18	13175
  BCL11A-11115	+	GGAGAGAAGAAAGGGGUGG	19	13176
  BCL11A-11116	+	GGGAGAGAAGAAAGGGGUGG	20	13177
  BCL11A-11117	+	CGGGAGAGAAGAAAGGGGUGG	21	13178
  BCL11A-11118	+	CCGGGAGAGAAGAAAGGGGUGG	22	13179
  BCL11A-11119	+	GCCGGGAGAGAAGAAAGGGGUGG	23	13180
  BCL11A-11120	+	GGCCGGGAGAGAAGAAAGGGGUGG	24	13181
  BCL11A-11121	+	AAGGGGUGGCAGGGGUGG	18	13182
  BCL11A-11122	+	AAAGGGGUGGCAGGGGUGG	19	13183
  BCL11A-11123	+	GAAAGGGGUGGCAGGGGUGG	20	13184
  BCL11A-11124	+	AGAAAGGGGUGGCAGGGGUGG	21	13185
  BCL11A-11125	+	AAGAAAGGGGUGGCAGGGGUGG	22	13186
  BCL11A-11126	+	GAAGAAAGGGGUGGCAGGGGUGG	23	13187
  BCL11A-11127	+	AGAAGAAAGGGGUGGCAGGGGUGG	24	13188
  BCL11A-11128	+	AGGGAAGAUGAAUUGUGG	18	13189
  BCL11A-11129	+	CAGGGAAGAUGAAUUGUGG	19	13190
  BCL11A-11130	+	GCAGGGAAGAUGAAUUGUGG	20	13191
  BCL11A-11131	+	CGCAGGGAAGAUGAAUUGUGG	21	13192
  BCL11A-11132	+	GCGCAGGGAAGAUGAAUUGUGG	22	13193
  BCL11A-11133	+	GGCGCAGGGAAGAUGAAUUGUGG	23	13194
  BCL11A-11134	+	UGGCGCAGGGAAGAUGAAUUGUGG	24	13195
  BCL11A-6524	+	UGCUUGCGGCGAGACAUG	18	13196
  BCL11A-6525	+	UUGCUUGCGGCGAGACAUG	19	13197
  BCL11A-6526	+	CUUGCUUGCGGCGAGACAUG	20	13198
  BCL11A-6527	+	CCUUGCUUGCGGCGAGACAUG	21	13199
  BCL11A-6528	+	GCCUUGCUUGCGGCGAGACAUG	22	13200
  BCL11A-6529	+	UGCCUUGCUUGCGGCGAGACAUG	23	13201
  BCL11A-6530	+	UUGCCUUGCUUGCGGCGAGACAUG	24	13202
  BCL11A-6544	+	GCGAGACAUGGUGGGCUG	18	13203
  BCL11A-6545	+	GGCGAGACAUGGUGGGCUG	19	13204
  BCL11A-5361	+	CGGCGAGACAUGGUGGGCUG	20	13205
  BCL11A-6546	+	GCGGCGAGACAUGGUGGGCUG	21	13206
  BCL11A-6547	+	UGCGGCGAGACAUGGUGGGCUG	22	13207
  BCL11A-6548	+	UUGCGGCGAGACAUGGUGGGCUG	23	13208
  BCL11A-6549	+	CUUGCGGCGAGACAUGGUGGGCUG	24	13209
  BCL11A-6550	+	UUCCCGUUUGCUUAAGUG	18	13210
  BCL11A-6551	+	AUUCCCGUUUGCUUAAGUG	19	13211
  BCL11A-6552	+	AAUUCCCGUUUGCUUAAGUG	20	13212
  BCL11A-6553	+	GAAUUCCCGUUUGCUUAAGUG	21	13213
  BCL11A-6554	+	AGAAUUCCCGUUUGCUUAAGUG	22	13214
  BCL11A-6555	+	GAGAAUUCCCGUUUGCUUAAGUG	23	13215
  BCL11A-6556	+	CGAGAAUUCCCGUUUGCUUAAGUG	24	13216
  BCL11A-11135	+	ACAAGCCAAUGGCCAGUG	18	13217
  BCL11A-11136	+	GACAAGCCAAUGGCCAGUG	19	13218
  BCL11A-9773	+	GGACAAGCCAAUGGCCAGUG	20	13219
  BCL11A-11137	+	AGGACAAGCCAAUGGCCAGUG	21	13220
  BCL11A-11138	+	CAGGACAAGCCAAUGGCCAGUG	22	13221
  BCL11A-11139	+	CCAGGACAAGCCAAUGGCCAGUG	23	13222
  BCL11A-11140	+	ACCAGGACAAGCCAAUGGCCAGUG	24	13223
  BCL11A-11141	+	UGCGGGGAGGGGGAGGUG	18	13224
  BCL11A-11142	+	GUGCGGGGAGGGGGAGGUG	19	13225
  BCL11A-9774	+	AGUGCGGGGAGGGGGAGGUG	20	13226
  BCL11A-11143	+	CAGUGCGGGGAGGGGGAGGUG	21	13227
  BCL11A-11144	+	CCAGUGCGGGGAGGGGGAGGUG	22	13228
  BCL11A-11145	+	GCCAGUGCGGGGAGGGGGAGGUG	23	13229
  BCL11A-11146	+	GGCCAGUGCGGGGAGGGGGAGGUG	24	13230
  BCL11A-11147	+	GGGUGGGAGGAAAGGGUG	18	13231
  BCL11A-11148	+	GGGGUGGGAGGAAAGGGUG	19	13232
  BCL11A-9775	+	AGGGGUGGGAGGAAAGGGUG	20	13233
  BCL11A-11149	+	CAGGGGUGGGAGGAAAGGGUG	21	13234
  BCL11A-11150	+	GCAGGGGUGGGAGGAAAGGGUG	22	13235
  BCL11A-11151	+	GGCAGGGGUGGGAGGAAAGGGUG	23	13236
  BCL11A-11152	+	UGGCAGGGGUGGGAGGAAAGGGUG	24	13237
  BCL11A-11153	+	CGCAGGGAAGAUGAAUUG	18	13238
  BCL11A-11154	+	GCGCAGGGAAGAUGAAUUG	19	13239
  BCL11A-9777	+	GGCGCAGGGAAGAUGAAUUG	20	13240
  BCL11A-11155	+	UGGCGCAGGGAAGAUGAAUUG	21	13241
  BCL11A-11156	+	AUGGCGCAGGGAAGAUGAAUUG	22	13242
  BCL11A-11157	+	GAUGGCGCAGGGAAGAUGAAUUG	23	13243
  BCL11A-11158	+	AGAUGGCGCAGGGAAGAUGAAUUG	24	13244
  BCL11A-11159	+	UUGACAUCCAAAAUAAAU	18	13245
  BCL11A-11160	+	UUUGACAUCCAAAAUAAAU	19	13246
  BCL11A-11161	+	UUUUGACAUCCAAAAUAAAU	20	13247
  BCL11A-11162	+	CUUUUGACAUCCAAAAUAAAU	21	13248
  BCL11A-11163	+	CCUUUUGACAUCCAAAAUAAAU	22	13249
  BCL11A-11164	+	GCCUUUUGACAUCCAAAAUAAAU	23	13250
  BCL11A-11165	+	UGCCUUUUGACAUCCAAAAUAAAU	24	13251
  BCL11A-11166	+	ACACCAAUGGACACACAU	18	13252
  BCL11A-11167	+	CACACCAAUGGACACACAU	19	13253
  BCL11A-11168	+	UCACACCAAUGGACACACAU	20	13254
  BCL11A-11169	+	CUCACACCAAUGGACACACAU	21	13255
  BCL11A-11170	+	GCUCACACCAAUGGACACACAU	22	13256
  BCL11A-11171	+	AGCUCACACCAAUGGACACACAU	23	13257
  BCL11A-11172	+	AAGCUCACACCAAUGGACACACAU	24	13258
  BCL11A-11173	+	CGACGGCUCGGUUCACAU	18	13259
  BCL11A-11174	+	ACGACGGCUCGGUUCACAU	19	13260
  BCL11A-9582	+	GACGACGGCUCGGUUCACAU	20	13261
  BCL11A-11175	+	GGACGACGGCUCGGUUCACAU	21	13262
  BCL11A-11176	+	CGGACGACGGCUCGGUUCACAU	22	13263
  BCL11A-11177	+	GCGGACGACGGCUCGGUUCACAU	23	13264
  BCL11A-11178	+	GGCGGACGACGGCUCGGUUCACAU	24	13265
  BCL11A-11179	+	UGCGGACGUGACGUCCCU	18	13266
  BCL11A-11180	+	GUGCGGACGUGACGUCCCU	19	13267
  BCL11A-11181	+	AGUGCGGACGUGACGUCCCU	20	13268
  BCL11A-11182	+	AAGUGCGGACGUGACGUCCCU	21	13269
  BCL11A-11183	+	CAAGUGCGGACGUGACGUCCCU	22	13270
  BCL11A-11184	+	UCAAGUGCGGACGUGACGUCCCU	23	13271
  BCL11A-11185	+	UUCAAGUGCGGACGUGACGUCCCU	24	13272
  BCL11A-6618	+	GGCGAGACAUGGUGGGCU	18	13273
  BCL11A-6619	+	CGGCGAGACAUGGUGGGCU	19	13274
  BCL11A-6620	+	GCGGCGAGACAUGGUGGGCU	20	13275
  BCL11A-6621	+	UGCGGCGAGACAUGGUGGGCU	21	13276
  BCL11A-6622	+	UUGCGGCGAGACAUGGUGGGCU	22	13277
  BCL11A-6623	+	CUUGCGGCGAGACAUGGUGGGCU	23	13278
  BCL11A-6624	+	GCUUGCGGCGAGACAUGGUGGGCU	24	13279
  BCL11A-11186	+	CUCUUUUACCUCGACUCU	18	13280
  BCL11A-11187	+	UCUCUUUUACCUCGACUCU	19	13281
  BCL11A-9585	+	AUCUCUUUUACCUCGACUCU	20	13282
  BCL11A-11188	+	UAUCUCUUUUACCUCGACUCU	21	13283
  BCL11A-11189	+	UUAUCUCUUUUACCUCGACUCU	22	13284
  BCL11A-11190	+	UUUAUCUCUUUUACCUCGACUCU	23	13285
  BCL11A-11191	+	CUUUAUCUCUUUUACCUCGACUCU	24	13286
  BCL11A-11192	+	UGAGCUGCAAGUUCAAGU	18	13287
  BCL11A-11193	+	CUGAGCUGCAAGUUCAAGU	19	13288
  BCL11A-11194	+	CCUGAGCUGCAAGUUCAAGU	20	13289
  BCL11A-11195	+	CCCUGAGCUGCAAGUUCAAGU	21	13290
  BCL11A-11196	+	CCCCUGAGCUGCAAGUUCAAGU	22	13291
  BCL11A-11197	+	CCCCCUGAGCUGCAAGUUCAAGU	23	13292
  BCL11A-11198	+	CCCCCCUGAGCUGCAAGUUCAAGU	24	13293
  BCL11A-11199	+	GACAAGCCAAUGGCCAGU	18	13294
  BCL11A-11200	+	GGACAAGCCAAUGGCCAGU	19	13295
  BCL11A-11201	+	AGGACAAGCCAAUGGCCAGU	20	13296
  BCL11A-11202	+	CAGGACAAGCCAAUGGCCAGU	21	13297
  BCL11A-11203	+	CCAGGACAAGCCAAUGGCCAGU	22	13298
  BCL11A-11204	+	ACCAGGACAAGCCAAUGGCCAGU	23	13299
  BCL11A-11205	+	GACCAGGACAAGCCAAUGGCCAGU	24	13300
  BCL11A-11206	+	CCCUGCGAACUUGAACGU	18	13301
  BCL11A-11207	+	UCCCUGCGAACUUGAACGU	19	13302
  BCL11A-11208	+	GUCCCUGCGAACUUGAACGU	20	13303
  BCL11A-11209	+	CGUCCCUGCGAACUUGAACGU	21	13304
  BCL11A-11210	+	ACGUCCCUGCGAACUUGAACGU	22	13305
  BCL11A-11211	+	GACGUCCCUGCGAACUUGAACGU	23	13306
  BCL11A-11212	+	UGACGUCCCUGCGAACUUGAACGU	24	13307
  BCL11A-11213	+	GUGCGGGGAGGGGGAGGU	18	13308
  BCL11A-11214	+	AGUGCGGGGAGGGGGAGGU	19	13309
  BCL11A-11215	+	CAGUGCGGGGAGGGGGAGGU	20	13310
  BCL11A-11216	+	CCAGUGCGGGGAGGGGGAGGU	21	13311
  BCL11A-11217	+	GCCAGUGCGGGGAGGGGGAGGU	22	13312
  BCL11A-11218	+	GGCCAGUGCGGGGAGGGGGAGGU	23	13313
  BCL11A-11219	+	UGGCCAGUGCGGGGAGGGGGAGGU	24	13314
  BCL11A-11220	+	GGGGUGGGAGGAAAGGGU	18	13315
  BCL11A-11221	+	AGGGGUGGGAGGAAAGGGU	19	13316
  BCL11A-9784	+	CAGGGGUGGGAGGAAAGGGU	20	13317
  BCL11A-11222	+	GCAGGGGUGGGAGGAAAGGGU	21	13318
  BCL11A-11223	+	GGCAGGGGUGGGAGGAAAGGGU	22	13319
  BCL11A-11224	+	UGGCAGGGGUGGGAGGAAAGGGU	23	13320
  BCL11A-11225	+	GUGGCAGGGGUGGGAGGAAAGGGU	24	13321
  BCL11A-11226	+	ACAUCGGGAGAGCCGGGU	18	13322
  BCL11A-11227	+	CACAUCGGGAGAGCCGGGU	19	13323
  BCL11A-11228	+	UCACAUCGGGAGAGCCGGGU	20	13324
  BCL11A-11229	+	UUCACAUCGGGAGAGCCGGGU	21	13325
  BCL11A-11230	+	GUUCACAUCGGGAGAGCCGGGU	22	13326
  BCL11A-11231	+	GGUUCACAUCGGGAGAGCCGGGU	23	13327
  BCL11A-11232	+	CGGUUCACAUCGGGAGAGCCGGGU	24	13328
  BCL11A-11233	+	GAAAGGGGUGGCAGGGGU	18	13329
  BCL11A-11234	+	AGAAAGGGGUGGCAGGGGU	19	13330
  BCL11A-9785	+	AAGAAAGGGGUGGCAGGGGU	20	13331
  BCL11A-11235	+	GAAGAAAGGGGUGGCAGGGGU	21	13332
  BCL11A-11236	+	AGAAGAAAGGGGUGGCAGGGGU	22	13333
  BCL11A-11237	+	GAGAAGAAAGGGGUGGCAGGGGU	23	13334
  BCL11A-11238	+	AGAGAAGAAAGGGGUGGCAGGGGU	24	13335
  BCL11A-11239	+	GCAGGGAAGAUGAAUUGU	18	13336
  BCL11A-11240	+	CGCAGGGAAGAUGAAUUGU	19	13337
  BCL11A-9786	+	GCGCAGGGAAGAUGAAUUGU	20	13338
  BCL11A-11241	+	GGCGCAGGGAAGAUGAAUUGU	21	13339
  BCL11A-11242	+	UGGCGCAGGGAAGAUGAAUUGU	22	13340
  BCL11A-11243	+	AUGGCGCAGGGAAGAUGAAUUGU	23	13341
  BCL11A-11244	+	GAUGGCGCAGGGAAGAUGAAUUGU	24	13342
  BCL11A-11245	+	GCGCAGGGAAGAUGAAUU	18	13343
  BCL11A-11246	+	GGCGCAGGGAAGAUGAAUU	19	13344
  BCL11A-11247	+	UGGCGCAGGGAAGAUGAAUU	20	13345
  BCL11A-11248	+	AUGGCGCAGGGAAGAUGAAUU	21	13346
  BCL11A-11249	+	GAUGGCGCAGGGAAGAUGAAUU	22	13347
  BCL11A-11250	+	AGAUGGCGCAGGGAAGAUGAAUU	23	13348
  BCL11A-11251	+	AAGAUGGCGCAGGGAAGAUGAAUU	24	13349
  BCL11A-11252	-	GCAGGACUAGAAGCAAAA	18	13350
  BCL11A-11253	-	CGCAGGACUAGAAGCAAAA	19	13351
  BCL11A-11254	-	GCGCAGGACUAGAAGCAAAA	20	13352
  BCL11A-11255	-	CGCGCAGGACUAGAAGCAAAA	21	13353
  BCL11A-11256	-	GCGCGCAGGACUAGAAGCAAAA	22	13354
  BCL11A-11257	-	AGCGCGCAGGACUAGAAGCAAAA	23	13355
  BCL11A-11258	-	GAGCGCGCAGGACUAGAAGCAAAA	24	13356
  BCL11A-6678	-	CCCCAGCACUUAAGCAAA	18	13357
  BCL11A-6679	-	ACCCCAGCACUUAAGCAAA	19	13358
  BCL11A-5443	-	AACCCCAGCACUUAAGCAAA	20	13359
  BCL11A-6680	-	AAACCCCAGCACUUAAGCAAA	21	13360
  BCL11A-6681	-	CAAACCCCAGCACUUAAGCAAA	22	13361
  BCL11A-6682	-	GCAAACCCCAGCACUUAAGCAAA	23	13362
  BCL11A-6683	-	GGCAAACCCCAGCACUUAAGCAAA	24	13363
  BCL11A-11259	-	CGAGGUAAAAGAGAUAAA	18	13364
  BCL11A-11260	-	UCGAGGUAAAAGAGAUAAA	19	13365
  BCL11A-9693	-	GUCGAGGUAAAAGAGAUAAA	20	13366
  BCL11A-11261	-	AGUCGAGGUAAAAGAGAUAAA	21	13367
  BCL11A-11262	-	GAGUCGAGGUAAAAGAGAUAAA	22	13368
  BCL11A-11263	-	AGAGUCGAGGUAAAAGAGAUAAA	23	13369
  BCL11A-11264	-	GAGAGUCGAGGUAAAAGAGAUAAA	24	13370
  BCL11A-6698	-	ACCCCAGCACUUAAGCAA	18	13371
  BCL11A-6699	-	AACCCCAGCACUUAAGCAA	19	13372
  BCL11A-6700	-	AAACCCCAGCACUUAAGCAA	20	13373
  BCL11A-6701	-	CAAACCCCAGCACUUAAGCAA	21	13374
  BCL11A-6702	-	GCAAACCCCAGCACUUAAGCAA	22	13375
  BCL11A-6703	-	GGCAAACCCCAGCACUUAAGCAA	23	13376
  BCL11A-6704	-	AGGCAAACCCCAGCACUUAAGCAA	24	13377
  BCL11A-11265	-	CGGCUCUCCCGAUGUGAA	18	13378
  BCL11A-11266	-	CCGGCUCUCCCGAUGUGAA	19	13379
  BCL11A-11267	-	CCCGGCUCUCCCGAUGUGAA	20	13380
  BCL11A-11268	-	ACCCGGCUCUCCCGAUGUGAA	21	13381
  BCL11A-11269	-	AACCCGGCUCUCCCGAUGUGAA	22	13382
  BCL11A-11270	-	UAACCCGGCUCUCCCGAUGUGAA	23	13383
  BCL11A-11271	-	CUAACCCGGCUCUCCCGAUGUGAA	24	13384
  BCL11A-11272	-	UCGAGGUAAAAGAGAUAA	18	13385
  BCL11A-11273	-	GUCGAGGUAAAAGAGAUAA	19	13386
  BCL11A-9699	-	AGUCGAGGUAAAAGAGAUAA	20	13387
  BCL11A-11274	-	GAGUCGAGGUAAAAGAGAUAA	21	13388
  BCL11A-11275	-	AGAGUCGAGGUAAAAGAGAUAA	22	13389
  BCL11A-11276	-	GAGAGUCGAGGUAAAAGAGAUAA	23	13390
  BCL11A-11277	-	CGAGAGUCGAGGUAAAAGAGAUAA	24	13391
  BCL11A-11278	-	CUCCGAGAGUCGAGGUAA	18	13392
  BCL11A-11279	-	CCUCCGAGAGUCGAGGUAA	19	13393
  BCL11A-11280	-	ACCUCCGAGAGUCGAGGUAA	20	13394
  BCL11A-11281	-	AACCUCCGAGAGUCGAGGUAA	21	13395
  BCL11A-11282	-	AAACCUCCGAGAGUCGAGGUAA	22	13396
  BCL11A-11283	-	AAAACCUCCGAGAGUCGAGGUAA	23	13397
  BCL11A-11284	-	AAAAACCUCCGAGAGUCGAGGUAA	24	13398
  BCL11A-11285	-	ACUUGAACUUGCAGCUCA	18	13399
  BCL11A-11286	-	CACUUGAACUUGCAGCUCA	19	13400
  BCL11A-9705	-	GCACUUGAACUUGCAGCUCA	20	13401
  BCL11A-11287	-	CGCACUUGAACUUGCAGCUCA	21	13402
  BCL11A-11288	-	CCGCACUUGAACUUGCAGCUCA	22	13403
  BCL11A-11289	-	UCCGCACUUGAACUUGCAGCUCA	23	13404
  BCL11A-11290	-	GUCCGCACUUGAACUUGCAGCUCA	24	13405
  BCL11A-11291	-	GCAAAAGCGAGGGGGAGA	18	13406
  BCL11A-11292	-	AGCAAAAGCGAGGGGGAGA	19	13407
  BCL11A-4934	-	AAGCAAAAGCGAGGGGGAGA	20	13408
  BCL11A-11293	-	GAAGCAAAAGCGAGGGGGAGA	21	13409
  BCL11A-11294	-	AGAAGCAAAAGCGAGGGGGAGA	22	13410
  BCL11A-11295	-	UAGAAGCAAAAGCGAGGGGGAGA	23	13411
  BCL11A-11296	-	CUAGAAGCAAAAGCGAGGGGGAGA	24	13412
  BCL11A-11297	-	GACUAGAAGCAAAAGCGA	18	13413
  BCL11A-11298	-	GGACUAGAAGCAAAAGCGA	19	13414
  BCL11A-9710	-	AGGACUAGAAGCAAAAGCGA	20	13415
  BCL11A-11299	-	CAGGACUAGAAGCAAAAGCGA	21	13416
  BCL11A-11300	-	GCAGGACUAGAAGCAAAAGCGA	22	13417
  BCL11A-11301	-	CGCAGGACUAGAAGCAAAAGCGA	23	13418
  BCL11A-11302	-	GCGCAGGACUAGAAGCAAAAGCGA	24	13419
  BCL11A-11303	-	AAGCAAAAGCGAGGGGGA	18	13420
  BCL11A-11304	-	GAAGCAAAAGCGAGGGGGA	19	13421
  BCL11A-4972	-	AGAAGCAAAAGCGAGGGGGA	20	13422
  BCL11A-11305	-	UAGAAGCAAAAGCGAGGGGGA	21	13423
  BCL11A-11306	-	CUAGAAGCAAAAGCGAGGGGGA	22	13424
  BCL11A-11307	-	ACUAGAAGCAAAAGCGAGGGGGA	23	13425
  BCL11A-11308	-	GACUAGAAGCAAAAGCGAGGGGGA	24	13426
  BCL11A-11309	-	GUCGAGGUAAAAGAGAUA	18	13427
  BCL11A-11310	-	AGUCGAGGUAAAAGAGAUA	19	13428
  BCL11A-11311	-	GAGUCGAGGUAAAAGAGAUA	20	13429
  BCL11A-11312	-	AGAGUCGAGGUAAAAGAGAUA	21	13430
  BCL11A-11313	-	GAGAGUCGAGGUAAAAGAGAUA	22	13431
  BCL11A-11314	-	CGAGAGUCGAGGUAAAAGAGAUA	23	13432
  BCL11A-11315	-	CCGAGAGUCGAGGUAAAAGAGAUA	24	13433
  BCL11A-11316	-	GGGACGUCACGUCCGCAC	18	13434
  BCL11A-11317	-	AGGGACGUCACGUCCGCAC	19	13435
  BCL11A-11318	-	CAGGGACGUCACGUCCGCAC	20	13436
  BCL11A-11319	-	GCAGGGACGUCACGUCCGCAC	21	13437
  BCL11A-11320	-	CGCAGGGACGUCACGUCCGCAC	22	13438
  BCL11A-11321	-	UCGCAGGGACGUCACGUCCGCAC	23	13439
  BCL11A-11322	-	UUCGCAGGGACGUCACGUCCGCAC	24	13440
  BCL11A-11323	-	AUAAUUAUUAAUAAUCAC	18	13441
  BCL11A-11324	-	AAUAAUUAUUAAUAAUCAC	19	13442
  BCL11A-11325	-	UAAUAAUUAUUAAUAAUCAC	20	13443
  BCL11A-11326	-	AUAAUAAUUAUUAAUAAUCAC	21	13444
  BCL11A-11327	-	AAUAAUAAUUAUUAAUAAUCAC	22	13445
  BCL11A-11328	-	UAAUAAUAAUUAUUAAUAAUCAC	23	13446
  BCL11A-11329	-	GUAAUAAUAAUUAUUAAUAAUCAC	24	13447
  BCL11A-11330	-	CAUUUUUAAAUUUUUCAC	18	13448
  BCL11A-11331	-	GCAUUUUUAAAUUUUUCAC	19	13449
  BCL11A-11332	-	UGCAUUUUUAAAUUUUUCAC	20	13450
  BCL11A-11333	-	AUGCAUUUUUAAAUUUUUCAC	21	13451
  BCL11A-11334	-	CAUGCAUUUUUAAAUUUUUCAC	22	13452
  BCL11A-11335	-	GCAUGCAUUUUUAAAUUUUUCAC	23	13453
  BCL11A-11336	-	UGCAUGCAUUUUUAAAUUUUUCAC	24	13454
  BCL11A-11337	-	CACGAGAGCGCGCAGGAC	18	13455
  BCL11A-11338	-	UCACGAGAGCGCGCAGGAC	19	13456
  BCL11A-11339	-	AUCACGAGAGCGCGCAGGAC	20	13457
  BCL11A-11340	-	AAUCACGAGAGCGCGCAGGAC	21	13458
  BCL11A-11341	-	UAAUCACGAGAGCGCGCAGGAC	22	13459
  BCL11A-11342	-	AUAAUCACGAGAGCGCGCAGGAC	23	13460
  BCL11A-11343	-	AAUAAUCACGAGAGCGCGCAGGAC	24	13461
  BCL11A-11344	-	UCGGCCCGCCCCUCCCCC	18	13462
  BCL11A-11345	-	CUCGGCCCGCCCCUCCCCC	19	13463
  BCL11A-9716	-	CCUCGGCCCGCCCCUCCCCC	20	13464
  BCL11A-11346	-	CCCUCGGCCCGCCCCUCCCCC	21	13465
  BCL11A-11347	-	CCCCUCGGCCCGCCCCUCCCCC	22	13466
  BCL11A-11348	-	UCCCCUCGGCCCGCCCCUCCCCC	23	13467
  BCL11A-11349	-	CUCCCCUCGGCCCGCCCCUCCCCC	24	13468
  BCL11A-11350	-	CUCGGCCCGCCCCUCCCC	18	13469
  BCL11A-11351	-	CCUCGGCCCGCCCCUCCCC	19	13470
  BCL11A-9717	-	CCCUCGGCCCGCCCCUCCCC	20	13471
  BCL11A-11352	-	CCCCUCGGCCCGCCCCUCCCC	21	13472
  BCL11A-11353	-	UCCCCUCGGCCCGCCCCUCCCC	22	13473
  BCL11A-11354	-	CUCCCCUCGGCCCGCCCCUCCCC	23	13474
  BCL11A-11355	-	CCUCCCCUCGGCCCGCCCCUCCCC	24	13475
  BCL11A-11356	-	CCUCGGCCCGCCCCUCCC	18	13476
  BCL11A-11357	-	CCCUCGGCCCGCCCCUCCC	19	13477
  BCL11A-11358	-	CCCCUCGGCCCGCCCCUCCC	20	13478
  BCL11A-11359	-	UCCCCUCGGCCCGCCCCUCCC	21	13479
  BCL11A-11360	-	CUCCCCUCGGCCCGCCCCUCCC	22	13480
  BCL11A-11361	-	CCUCCCCUCGGCCCGCCCCUCCC	23	13481
  BCL11A-11362	-	CCCUCCCCUCGGCCCGCCCCUCCC	24	13482
  BCL11A-11363	-	GGGCCGCGUCUGGCGUCC	18	13483
  BCL11A-11364	-	GGGGCCGCGUCUGGCGUCC	19	13484
  BCL11A-11365	-	GGGGGCCGCGUCUGGCGUCC	20	13485
  BCL11A-11366	-	CGGGGGCCGCGUCUGGCGUCC	21	13486
  BCL11A-11367	-	CCGGGGGCCGCGUCUGGCGUCC	22	13487
  BCL11A-11368	-	CCCGGGGGCCGCGUCUGGCGUCC	23	13488
  BCL11A-11369	-	CCCCGGGGGCCGCGUCUGGCGUCC	24	13489
  BCL11A-11370	-	AGGACUAGAAGCAAAAGC	18	13490
  BCL11A-11371	-	CAGGACUAGAAGCAAAAGC	19	13491
  BCL11A-11372	-	GCAGGACUAGAAGCAAAAGC	20	13492
  BCL11A-11373	-	CGCAGGACUAGAAGCAAAAGC	21	13493
  BCL11A-11374	-	GCGCAGGACUAGAAGCAAAAGC	22	13494
  BCL11A-11375	-	CGCGCAGGACUAGAAGCAAAAGC	23	13495
  BCL11A-11376	-	GCGCGCAGGACUAGAAGCAAAAGC	24	13496
  BCL11A-11377	-	CCUGACGUUCAAGUUCGC	18	13497
  BCL11A-11378	-	UCCUGACGUUCAAGUUCGC	19	13498
  BCL11A-9566	-	CUCCUGACGUUCAAGUUCGC	20	13499
  BCL11A-11379	-	ACUCCUGACGUUCAAGUUCGC	21	13500
  BCL11A-11380	-	GACUCCUGACGUUCAAGUUCGC	22	13501
  BCL11A-11381	-	AGACUCCUGACGUUCAAGUUCGC	23	13502
  BCL11A-11382	-	CAGACUCCUGACGUUCAAGUUCGC	24	13503
  BCL11A-11383	-	UAAUAAUUAUUAAUAAUC	18	13504
  BCL11A-11384	-	AUAAUAAUUAUUAAUAAUC	19	13505
  BCL11A-11385	-	AAUAAUAAUUAUUAAUAAUC	20	13506
  BCL11A-11386	-	UAAUAAUAAUUAUUAAUAAUC	21	13507
  BCL11A-11387	-	GUAAUAAUAAUUAUUAAUAAUC	22	13508
  BCL11A-11388	-	AGUAAUAAUAAUUAUUAAUAAUC	23	13509
  BCL11A-11389	-	UAGUAAUAAUAAUUAUUAAUAAUC	24	13510
  BCL11A-11390	-	AAAAACCCUCAUCCCAUC	18	13511
  BCL11A-11391	-	AAAAAACCCUCAUCCCAUC	19	13512
  BCL11A-9730	-	GAAAAAACCCUCAUCCCAUC	20	13513
  BCL11A-11392	-	GGAAAAAACCCUCAUCCCAUC	21	13514
  BCL11A-11393	-	GGGAAAAAACCCUCAUCCCAUC	22	13515
  BCL11A-11394	-	GGGGAAAAAACCCUCAUCCCAUC	23	13516
  BCL11A-11395	-	GGGGGAAAAAACCCUCAUCCCAUC	24	13517
  BCL11A-11396	-	CACUUGAACUUGCAGCUC	18	13518
  BCL11A-11397	-	GCACUUGAACUUGCAGCUC	19	13519
  BCL11A-9569	-	CGCACUUGAACUUGCAGCUC	20	13520
  BCL11A-11398	-	CCGCACUUGAACUUGCAGCUC	21	13521
  BCL11A-11399	-	UCCGCACUUGAACUUGCAGCUC	22	13522
  BCL11A-11400	-	GUCCGCACUUGAACUUGCAGCUC	23	13523
  BCL11A-11401	-	CGUCCGCACUUGAACUUGCAGCUC	24	13524
  BCL11A-11402	-	UGCAUUUUUAAAUUUUUC	18	13525
  BCL11A-11403	-	AUGCAUUUUUAAAUUUUUC	19	13526
  BCL11A-11404	-	CAUGCAUUUUUAAAUUUUUC	20	13527
  BCL11A-11405	-	GCAUGCAUUUUUAAAUUUUUC	21	13528
  BCL11A-11406	-	UGCAUGCAUUUUUAAAUUUUUC	22	13529
  BCL11A-11407	-	GUGCAUGCAUUUUUAAAUUUUUC	23	13530
  BCL11A-11408	-	UGUGCAUGCAUUUUUAAAUUUUUC	24	13531
  BCL11A-11409	-	GAGGUAAAAGAGAUAAAG	18	13532
  BCL11A-11410	-	CGAGGUAAAAGAGAUAAAG	19	13533
  BCL11A-9571	-	UCGAGGUAAAAGAGAUAAAG	20	13534
  BCL11A-11411	-	GUCGAGGUAAAAGAGAUAAAG	21	13535
  BCL11A-11412	-	AGUCGAGGUAAAAGAGAUAAAG	22	13536
  BCL11A-11413	-	GAGUCGAGGUAAAAGAGAUAAAG	23	13537
  BCL11A-11414	-	AGAGUCGAGGUAAAAGAGAUAAAG	24	13538
  BCL11A-11415	-	CUUGAACUUGCAGCUCAG	18	13539
  BCL11A-11416	-	ACUUGAACUUGCAGCUCAG	19	13540
  BCL11A-9738	-	CACUUGAACUUGCAGCUCAG	20	13541
  BCL11A-11417	-	GCACUUGAACUUGCAGCUCAG	21	13542
  BCL11A-11418	-	CGCACUUGAACUUGCAGCUCAG	22	13543
  BCL11A-11419	-	CCGCACUUGAACUUGCAGCUCAG	23	13544
  BCL11A-11420	-	UCCGCACUUGAACUUGCAGCUCAG	24	13545
  BCL11A-11421	-	GAGAAAAACCUCCGAGAG	18	13546
  BCL11A-11422	-	CGAGAAAAACCUCCGAGAG	19	13547
  BCL11A-11423	-	ACGAGAAAAACCUCCGAGAG	20	13548
  BCL11A-11424	-	CACGAGAAAAACCUCCGAGAG	21	13549
  BCL11A-11425	-	UCACGAGAAAAACCUCCGAGAG	22	13550
  BCL11A-11426	-	UUCACGAGAAAAACCUCCGAGAG	23	13551
  BCL11A-11427	-	UUUCACGAGAAAAACCUCCGAGAG	24	13552
  BCL11A-11428	-	ACUAGAAGCAAAAGCGAG	18	13553
  BCL11A-11429	-	GACUAGAAGCAAAAGCGAG	19	13554
  BCL11A-9739	-	GGACUAGAAGCAAAAGCGAG	20	13555
  BCL11A-11430	-	AGGACUAGAAGCAAAAGCGAG	21	13556
  BCL11A-11431	-	CAGGACUAGAAGCAAAAGCGAG	22	13557
  BCL11A-11432	-	GCAGGACUAGAAGCAAAAGCGAG	23	13558
  BCL11A-11433	-	CGCAGGACUAGAAGCAAAAGCGAG	24	13559
  BCL11A-11434	-	CGCGUGUGUGGGGGGGAG	18	13560
  BCL11A-11435	-	CCGCGUGUGUGGGGGGGAG	19	13561
  BCL11A-11436	-	UCCGCGUGUGUGGGGGGGAG	20	13562
  BCL11A-11437	-	GUCCGCGUGUGUGGGGGGGAG	21	13563
  BCL11A-11438	-	AGUCCGCGUGUGUGGGGGGGAG	22	13564
  BCL11A-11439	-	GAGUCCGCGUGUGUGGGGGGGAG	23	13565
  BCL11A-11440	-	AGAGUCCGCGUGUGUGGGGGGGAG	24	13566
  BCL11A-11441	-	GGCCGCGUCUGGCGUCCG	18	13567
  BCL11A-11442	-	GGGCCGCGUCUGGCGUCCG	19	13568
  BCL11A-9574	-	GGGGCCGCGUCUGGCGUCCG	20	13569
  BCL11A-11443	-	GGGGGCCGCGUCUGGCGUCCG	21	13570
  BCL11A-11444	-	CGGGGGCCGCGUCUGGCGUCCG	22	13571
  BCL11A-11445	-	CCGGGGGCCGCGUCUGGCGUCCG	23	13572
  BCL11A-11446	-	CCCGGGGGCCGCGUCUGGCGUCCG	24	13573
  BCL11A-11447	-	GGACUAGAAGCAAAAGCG	18	13574
  BCL11A-11448	-	AGGACUAGAAGCAAAAGCG	19	13575
  BCL11A-9748	-	CAGGACUAGAAGCAAAAGCG	20	13576
  BCL11A-11449	-	GCAGGACUAGAAGCAAAAGCG	21	13577
  BCL11A-11450	-	CGCAGGACUAGAAGCAAAAGCG	22	13578
  BCL11A-11451	-	GCGCAGGACUAGAAGCAAAAGCG	23	13579
  BCL11A-11452	-	CGCGCAGGACUAGAAGCAAAAGCG	24	13580
  BCL11A-11453	-	AAUAAUCACGAGAGCGCG	18	13581
  BCL11A-11454	-	UAAUAAUCACGAGAGCGCG	19	13582
  BCL11A-11455	-	UUAAUAAUCACGAGAGCGCG	20	13583
  BCL11A-11456	-	AUUAAUAAUCACGAGAGCGCG	21	13584
  BCL11A-11457	-	UAUUAAUAAUCACGAGAGCGCG	22	13585
  BCL11A-11458	-	UUAUUAAUAAUCACGAGAGCGCG	23	13586
  BCL11A-11459	-	AUUAUUAAUAAUCACGAGAGCGCG	24	13587
  BCL11A-11460	-	UCCUGACGUUCAAGUUCG	18	13588
  BCL11A-11461	-	CUCCUGACGUUCAAGUUCG	19	13589
  BCL11A-11462	-	ACUCCUGACGUUCAAGUUCG	20	13590
  BCL11A-11463	-	GACUCCUGACGUUCAAGUUCG	21	13591
  BCL11A-11464	-	AGACUCCUGACGUUCAAGUUCG	22	13592
  BCL11A-11465	-	CAGACUCCUGACGUUCAAGUUCG	23	13593
  BCL11A-11466	-	CCAGACUCCUGACGUUCAAGUUCG	24	13594
  BCL11A-11467	-	AGGUAAAAGAGAUAAAGG	18	13595
  BCL11A-11468	-	GAGGUAAAAGAGAUAAAGG	19	13596
  BCL11A-9753	-	CGAGGUAAAAGAGAUAAAGG	20	13597
  BCL11A-11469	-	UCGAGGUAAAAGAGAUAAAGG	21	13598
  BCL11A-11470	-	GUCGAGGUAAAAGAGAUAAAGG	22	13599
  BCL11A-11471	-	AGUCGAGGUAAAAGAGAUAAAGG	23	13600
  BCL11A-11472	-	GAGUCGAGGUAAAAGAGAUAAAGG	24	13601
  BCL11A-11473	-	CUAGAAGCAAAAGCGAGG	18	13602
  BCL11A-11474	-	ACUAGAAGCAAAAGCGAGG	19	13603
  BCL11A-9755	-	GACUAGAAGCAAAAGCGAGG	20	13604
  BCL11A-11475	-	GGACUAGAAGCAAAAGCGAGG	21	13605
  BCL11A-11476	-	AGGACUAGAAGCAAAAGCGAGG	22	13606
  BCL11A-11477	-	CAGGACUAGAAGCAAAAGCGAGG	23	13607
  BCL11A-11478	-	GCAGGACUAGAAGCAAAAGCGAGG	24	13608
  BCL11A-11479	-	AGAAGCAAAAGCGAGGGG	18	13609
  BCL11A-11480	-	UAGAAGCAAAAGCGAGGGG	19	13610
  BCL11A-11481	-	CUAGAAGCAAAAGCGAGGGG	20	13611
  BCL11A-11482	-	ACUAGAAGCAAAAGCGAGGGG	21	13612
  BCL11A-11483	-	GACUAGAAGCAAAAGCGAGGGG	22	13613
  BCL11A-11484	-	GGACUAGAAGCAAAAGCGAGGGG	23	13614
  BCL11A-11485	-	AGGACUAGAAGCAAAAGCGAGGGG	24	13615
  BCL11A-11486	-	GAGUCCGCGUGUGUGGGG	18	13616
  BCL11A-11487	-	AGAGUCCGCGUGUGUGGGG	19	13617
  BCL11A-9577	-	UAGAGUCCGCGUGUGUGGGG	20	13618
  BCL11A-11488	-	UUAGAGUCCGCGUGUGUGGGG	21	13619
  BCL11A-11489	-	UUUAGAGUCCGCGUGUGUGGGG	22	13620
  BCL11A-11490	-	UUUUAGAGUCCGCGUGUGUGGGG	23	13621
  BCL11A-11491	-	AUUUUAGAGUCCGCGUGUGUGGGG	24	13622
  BCL11A-11492	-	AGAGUCCGCGUGUGUGGG	18	13623
  BCL11A-11493	-	UAGAGUCCGCGUGUGUGGG	19	13624
  BCL11A-9769	-	UUAGAGUCCGCGUGUGUGGG	20	13625
  BCL11A-11494	-	UUUAGAGUCCGCGUGUGUGGG	21	13626
  BCL11A-11495	-	UUUUAGAGUCCGCGUGUGUGGG	22	13627
  BCL11A-11496	-	AUUUUAGAGUCCGCGUGUGUGGG	23	13628
  BCL11A-11497	-	CAUUUUAGAGUCCGCGUGUGUGGG	24	13629
  BCL11A-11498	-	UAGAGUCCGCGUGUGUGG	18	13630
  BCL11A-11499	-	UUAGAGUCCGCGUGUGUGG	19	13631
  BCL11A-9578	-	UUUAGAGUCCGCGUGUGUGG	20	13632
  BCL11A-11500	-	UUUUAGAGUCCGCGUGUGUGG	21	13633
  BCL11A-11501	-	AUUUUAGAGUCCGCGUGUGUGG	22	13634
  BCL11A-11502	-	CAUUUUAGAGUCCGCGUGUGUGG	23	13635
  BCL11A-11503	-	UCAUUUUAGAGUCCGCGUGUGUGG	24	13636
  BCL11A-11504	-	CGCUCGCUGCGGCCACUG	18	13637
  BCL11A-11505	-	GCGCUCGCUGCGGCCACUG	19	13638
  BCL11A-11506	-	GGCGCUCGCUGCGGCCACUG	20	13639
  BCL11A-11507	-	CGGCGCUCGCUGCGGCCACUG	21	13640
  BCL11A-11508	-	GCGGCGCUCGCUGCGGCCACUG	22	13641
  BCL11A-11509	-	CGCGGCGCUCGCUGCGGCCACUG	23	13642
  BCL11A-11510	-	CCGCGGCGCUCGCUGCGGCCACUG	24	13643
  BCL11A-11511	-	GGAUGUCAAAAGGCACUG	18	13644
  BCL11A-11512	-	UGGAUGUCAAAAGGCACUG	19	13645
  BCL11A-11513	-	UUGGAUGUCAAAAGGCACUG	20	13646
  BCL11A-11514	-	UUUGGAUGUCAAAAGGCACUG	21	13647
  BCL11A-11515	-	UUUUGGAUGUCAAAAGGCACUG	22	13648
  BCL11A-11516	-	AUUUUGGAUGUCAAAAGGCACUG	23	13649
  BCL11A-11517	-	UAUUUUGGAUGUCAAAAGGCACUG	24	13650
  BCL11A-11518	-	UUUUAGAGUCCGCGUGUG	18	13651
  BCL11A-11519	-	AUUUUAGAGUCCGCGUGUG	19	13652
  BCL11A-9581	-	CAUUUUAGAGUCCGCGUGUG	20	13653
  BCL11A-11520	-	UCAUUUUAGAGUCCGCGUGUG	21	13654
  BCL11A-11521	-	UUCAUUUUAGAGUCCGCGUGUG	22	13655
  BCL11A-11522	-	UUUCAUUUUAGAGUCCGCGUGUG	23	13656
  BCL11A-11523	-	CUUUCAUUUUAGAGUCCGCGUGUG	24	13657
  BCL11A-11524	-	UUAGAGUCCGCGUGUGUG	18	13658
  BCL11A-11525	-	UUUAGAGUCCGCGUGUGUG	19	13659
  BCL11A-9776	-	UUUUAGAGUCCGCGUGUGUG	20	13660
  BCL11A-11526	-	AUUUUAGAGUCCGCGUGUGUG	21	13661
  BCL11A-11527	-	CAUUUUAGAGUCCGCGUGUGUG	22	13662
  BCL11A-11528	-	UCAUUUUAGAGUCCGCGUGUGUG	23	13663
  BCL11A-11529	-	UUCAUUUUAGAGUCCGCGUGUGUG	24	13664
  BCL11A-11530	-	AAAAAACCCUCAUCCCAU	18	13665
  BCL11A-11531	-	GAAAAAACCCUCAUCCCAU	19	13666
  BCL11A-11532	-	GGAAAAAACCCUCAUCCCAU	20	13667
  BCL11A-11533	-	GGGAAAAAACCCUCAUCCCAU	21	13668
  BCL11A-11534	-	GGGGAAAAAACCCUCAUCCCAU	22	13669
  BCL11A-11535	-	GGGGGAAAAAACCCUCAUCCCAU	23	13670
  BCL11A-11536	-	AGGGGGAAAAAACCCUCAUCCCAU	24	13671
  BCL11A-11537	-	UAACCCGGCUCUCCCGAU	18	13672
  BCL11A-11538	-	CUAACCCGGCUCUCCCGAU	19	13673
  BCL11A-11539	-	UCUAACCCGGCUCUCCCGAU	20	13674
  BCL11A-11540	-	UUCUAACCCGGCUCUCCCGAU	21	13675
  BCL11A-11541	-	UUUCUAACCCGGCUCUCCCGAU	22	13676
  BCL11A-11542	-	CUUUCUAACCCGGCUCUCCCGAU	23	13677
  BCL11A-11543	-	UCUUUCUAACCCGGCUCUCCCGAU	24	13678
  BCL11A-11544	-	UUUUCACGAGAAAAACCU	18	13679
  BCL11A-11545	-	UUUUUCACGAGAAAAACCU	19	13680
  BCL11A-11546	-	AUUUUUCACGAGAAAAACCU	20	13681
  BCL11A-11547	-	AAUUUUUCACGAGAAAAACCU	21	13682
  BCL11A-11548	-	AAAUUUUUCACGAGAAAAACCU	22	13683
  BCL11A-11549	-	UAAAUUUUUCACGAGAAAAACCU	23	13684
  BCL11A-11550	-	UUAAAUUUUUCACGAGAAAAACCU	24	13685
  BCL11A-11551	-	GCACUUGAACUUGCAGCU	18	13686
  BCL11A-11552	-	CGCACUUGAACUUGCAGCU	19	13687
  BCL11A-11553	-	CCGCACUUGAACUUGCAGCU	20	13688
  BCL11A-11554	-	UCCGCACUUGAACUUGCAGCU	21	13689
  BCL11A-11555	-	GUCCGCACUUGAACUUGCAGCU	22	13690
  BCL11A-11556	-	CGUCCGCACUUGAACUUGCAGCU	23	13691
  BCL11A-11557	-	ACGUCCGCACUUGAACUUGCAGCU	24	13692
  BCL11A-11558	-	CUGAUGAAGAUAUUUUCU	18	13693
  BCL11A-11559	-	ACUGAUGAAGAUAUUUUCU	19	13694
  BCL11A-11560	-	CACUGAUGAAGAUAUUUUCU	20	13695
  BCL11A-11561	-	GCACUGAUGAAGAUAUUUUCU	21	13696
  BCL11A-11562	-	GGCACUGAUGAAGAUAUUUUCU	22	13697
  BCL11A-11563	-	AGGCACUGAUGAAGAUAUUUUCU	23	13698
  BCL11A-11564	-	AAGGCACUGAUGAAGAUAUUUUCU	24	13699
  BCL11A-11565	-	UGAUGUGUGUCCAUUGGU	18	13700
  BCL11A-11566	-	CUGAUGUGUGUCCAUUGGU	19	13701
  BCL11A-11567	-	CCUGAUGUGUGUCCAUUGGU	20	13702
  BCL11A-11568	-	CCCUGAUGUGUGUCCAUUGGU	21	13703
  BCL11A-11569	-	CCCCUGAUGUGUGUCCAUUGGU	22	13704
  BCL11A-11570	-	GCCCCUGAUGUGUGUCCAUUGGU	23	13705
  BCL11A-11571	-	AGCCCCUGAUGUGUGUCCAUUGGU	24	13706
  BCL11A-11572	-	AUUUUAGAGUCCGCGUGU	18	13707
  BCL11A-11573	-	CAUUUUAGAGUCCGCGUGU	19	13708
  BCL11A-11574	-	UCAUUUUAGAGUCCGCGUGU	20	13709
  BCL11A-11575	-	UUCAUUUUAGAGUCCGCGUGU	21	13710
  BCL11A-11576	-	UUUCAUUUUAGAGUCCGCGUGU	22	13711
  BCL11A-11577	-	CUUUCAUUUUAGAGUCCGCGUGU	23	13712
  BCL11A-11578	-	UCUUUCAUUUUAGAGUCCGCGUGU	24	13713
  BCL11A-11579	-	UUUAGAGUCCGCGUGUGU	18	13714
  BCL11A-11580	-	UUUUAGAGUCCGCGUGUGU	19	13715
  BCL11A-9586	-	AUUUUAGAGUCCGCGUGUGU	20	13716
  BCL11A-11581	-	CAUUUUAGAGUCCGCGUGUGU	21	13717
  BCL11A-11582	-	UCAUUUUAGAGUCCGCGUGUGU	22	13718
  BCL11A-11583	-	UUCAUUUUAGAGUCCGCGUGUGU	23	13719
  BCL11A-11584	-	UUUCAUUUUAGAGUCCGCGUGUGU	24	13720
  BCL11A-11585	-	AUUGCCGUGUAUGCACUU	18	13721
  BCL11A-11586	-	CAUUGCCGUGUAUGCACUU	19	13722
  BCL11A-11587	-	CCAUUGCCGUGUAUGCACUU	20	13723
  BCL11A-11588	-	ACCAUUGCCGUGUAUGCACUU	21	13724
  BCL11A-11589	-	AACCAUUGCCGUGUAUGCACUU	22	13725
  BCL11A-11590	-	GAACCAUUGCCGUGUAUGCACUU	23	13726
  BCL11A-11591	-	GGAACCAUUGCCGUGUAUGCACUU	24	13727

• Table 19D provides exemplary targeting domains for knocking down the BCL13A 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 1 kb 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 BCL11A gene (e.g., reduce or eliminate BCL11A gene expression, BCL13A protein function, or the level of BCL11A protein). One or more gRNA may be used to target an eiCas9 to the promoter region of the BCL11A gene.

• TABLE 19D
  4th Tier

  	DNA		Target Site	SEQ
  gRNA Name	Strand	Targeting Domain	Length	ID NO:
  BCL11A-11592	+	CUCACCUCUUUUCUCCCC	18	13728
  BCL11A-11593	+	UCUCACCUCUUUUCUCCCC	19	13729
  BCL11A-10076	+	GUCUCACCUCUUUUCUCCCC	20	13730
  BCL11A-11594	+	AGUCUCACCUCUUUUCUCCCC	21	13731
  BCL11A-11595	+	CAGUCUCACCUCUUUUCUCCCC	22	13732
  BCL11A-11596	+	CCAGUCUCACCUCUUUUCUCCCC	23	13733
  BCL11A-11597	+	GCCAGUCUCACCUCUUUUCUCCCC	24	13734
  BCL11A-11598	+	AAAAGAAAAAAAUAGAGC	18	13735
  BCL11A-11599	+	AAAAAGAAAAAAAUAGAGC	19	13736
  BCL11A-11600	+	AAAAAAGAAAAAAAUAGAGC	20	13737
  BCL11A-11601	+	CAAAAAAGAAAAAAAUAGAGC	21	13738
  BCL11A-11602	+	UCAAAAAAGAAAAAAAUAGAGC	22	13739
  BCL11A-11603	+	UUCAAAAAAGAAAAAAAUAGAGC	23	13740
  BCL11A-11604	+	AUUCAAAAAAGAAAAAAAUAGAGC	24	13741
  BCL11A-11605	+	GGCGGGGCGGGGGGGGAG	18	13742
  BCL11A-11606	+	UGGCGGGGCGGGGGGGGAG	19	13743
  BCL11A-10153	+	CUGGCGGGGCGGGGGGGGAG	20	13744
  BCL11A-11607	+	ACUGGCGGGGCGGGGGGGGAG	21	13745
  BCL11A-11608	+	AACUGGCGGGGCGGGGGGGGAG	22	13746
  BCL11A-11609	+	AAACUGGCGGGGCGGGGGGGGAG	23	13747
  BCL11A-11610	+	AAAACUGGCGGGGCGGGGGGGGAG	24	13748
  BCL11A-11611	+	AGGGAGCGCACGGCAACG	18	13749
  BCL11A-11612	+	GAGGGAGCGCACGGCAACG	19	13750
  BCL11A-10155	+	GGAGGGAGCGCACGGCAACG	20	13751
  BCL11A-11613	+	GGGAGGGAGCGCACGGCAACG	21	13752
  BCL11A-11614	+	UGGGAGGGAGCGCACGGCAACG	22	13753
  BCL11A-11615	+	GUGGGAGGGAGCGCACGGCAACG	23	13754
  BCL11A-11616	+	GGUGGGAGGGAGCGCACGGCAACG	24	13755
  BCL11A-11617	+	CCCCCCCAUUUUCUUACG	18	13756
  BCL11A-11618	+	ACCCCCCCAUUUUCUUACG	19	13757
  BCL11A-11619	+	UACCCCCCCAUUUUCUUACG	20	13758
  BCL11A-11620	+	CUACCCCCCCAUUUUCUUACG	21	13759
  BCL11A-11621	+	CCUACCCCCCCAUUUUCUUACG	22	13760
  BCL11A-11622	+	CCCUACCCCCCCAUUUUCUUACG	23	13761
  BCL11A-11623	+	UCCCUACCCCCCCAUUUUCUUACG	24	13762
  BCL11A-11624	+	GGGCGGAGGGAAGCCAGG	18	13763
  BCL11A-11625	+	CGGGCGGAGGGAAGCCAGG	19	13764
  BCL11A-11626	+	GCGGGCGGAGGGAAGCCAGG	20	13765
  BCL11A-11627	+	CGCGGGCGGAGGGAAGCCAGG	21	13766
  BCL11A-11628	+	GCGCGGGCGGAGGGAAGCCAGG	22	13767
  BCL11A-11629	+	AGCGCGGGCGGAGGGAAGCCAGG	23	13768
  BCL11A-11630	+	AAGCGCGGGCGGAGGGAAGCCAGG	24	13769
  BCL11A-11631	+	CGGAAAGGAGGAAAGAGG	18	13770
  BCL11A-11632	+	GCGGAAAGGAGGAAAGAGG	19	13771
  BCL11A-10187	+	GGCGGAAAGGAGGAAAGAGG	20	13772
  BCL11A-11633	+	CGGCGGAAAGGAGGAAAGAGG	21	13773
  BCL11A-11634	+	GCGGCGGAAAGGAGGAAAGAGG	22	13774
  BCL11A-11635	+	AGCGGCGGAAAGGAGGAAAGAGG	23	13775
  BCL11A-11636	+	AAGCGGCGGAAAGGAGGAAAGAGG	24	13776
  BCL11A-11637	+	AAACUGGCGGGGCGGGGG	18	13777
  BCL11A-11638	+	AAAACUGGCGGGGCGGGGG	19	13778
  BCL11A-10209	+	CAAAACUGGCGGGGCGGGGG	20	13779
  BCL11A-11639	+	GCAAAACUGGCGGGGCGGGGG	21	13780
  BCL11A-11640	+	UGCAAAACUGGCGGGGCGGGGG	22	13781
  BCL11A-11641	+	UUGCAAAACUGGCGGGGCGGGGG	23	13782
  BCL11A-11642	+	UUUGCAAAACUGGCGGGGCGGGGG	24	13783
  BCL11A-11643	+	CCACCCCCAGGUUUGCAU	18	13784
  BCL11A-11644	+	CCCACCCCCAGGUUUGCAU	19	13785
  BCL11A-11645	+	UCCCACCCCCAGGUUUGCAU	20	13786
  BCL11A-11646	+	CUCCCACCCCCAGGUUUGCAU	21	13787
  BCL11A-11647	+	GCUCCCACCCCCAGGUUUGCAU	22	13788
  BCL11A-11648	+	AGCUCCCACCCCCAGGUUUGCAU	23	13789
  BCL11A-11649	+	CAGCUCCCACCCCCAGGUUUGCAU	24	13790
  BCL11A-11650	+	GCCUAAGUUUGGAGGGCU	18	13791
  BCL11A-11651	+	AGCCUAAGUUUGGAGGGCU	19	13792
  BCL11A-11652	+	CAGCCUAAGUUUGGAGGGCU	20	13793
  BCL11A-11653	+	CCAGCCUAAGUUUGGAGGGCU	21	13794
  BCL11A-11654	+	UCCAGCCUAAGUUUGGAGGGCU	22	13795
  BCL11A-11655	+	AUCCAGCCUAAGUUUGGAGGGCU	23	13796
  BCL11A-11656	+	AAUCCAGCCUAAGUUUGGAGGGCU	24	13797
  BCL11A-11657	+	CCACUUUCUCACUAUUGU	18	13798
  BCL11A-11658	+	GCCACUUUCUCACUAUUGU	19	13799
  BCL11A-10251	+	UGCCACUUUCUCACUAUUGU	20	13800
  BCL11A-11659	+	GUGCCACUUUCUCACUAUUGU	21	13801
  BCL11A-11660	+	AGUGCCACUUUCUCACUAUUGU	22	13802
  BCL11A-11661	+	CAGUGCCACUUUCUCACUAUUGU	23	13803
  BCL11A-11662	+	ACAGUGCCACUUUCUCACUAUUGU	24	13804
  BCL11A-11663	-	UUAUUUCUCUUUUCGAAA	18	13805
  BCL11A-11664	-	UUUAUUUCUCUUUUCGAAA	19	13806
  BCL11A-10027	-	CUUUAUUUCUCUUUUCGAAA	20	13807
  BCL11A-11665	-	GCUUUAUUUCUCUUUUCGAAA	21	13808
  BCL11A-11666	-	CGCUUUAUUUCUCUUUUCGAAA	22	13809
  BCL11A-11667	-	CCGCUUUAUUUCUCUUUUCGAAA	23	13810
  BCL11A-11668	-	GCCGCUUUAUUUCUCUUUUCGAAA	24	13811
  BCL11A-11669	-	CGGCGGCGGGGAGGGGAA	18	13812
  BCL11A-11670	-	GCGGCGGCGGGGAGGGGAA	19	13813
  BCL11A-11671	-	GGCGGCGGCGGGGAGGGGAA	20	13814
  BCL11A-11672	-	CGGCGGCGGCGGGGAGGGGAA	21	13815
  BCL11A-11673	-	GCGGCGGCGGCGGGGAGGGGAA	22	13816
  BCL11A-11674	-	CGCGGCGGCGGCGGGGAGGGGAA	23	13817
  BCL11A-11675	-	GCGCGGCGGCGGCGGGGAGGGGAA	24	13818
  BCL11A-11676	-	UGGGGGGGUAGGGAGGGA	18	13819
  BCL11A-11677	-	AUGGGGGGGUAGGGAGGGA	19	13820
  BCL11A-11678	-	AAUGGGGGGGUAGGGAGGGA	20	13821
  BCL11A-11679	-	AAAUGGGGGGGUAGGGAGGGA	21	13822
  BCL11A-11680	-	AAAAUGGGGGGGUAGGGAGGGA	22	13823
  BCL11A-11681	-	GAAAAUGGGGGGGUAGGGAGGGA	23	13824
  BCL11A-11682	-	AGAAAAUGGGGGGGUAGGGAGGGA	24	13825
  BCL11A-11683	-	AAAAUGGGGGGGUAGGGA	18	13826
  BCL11A-11684	-	GAAAAUGGGGGGGUAGGGA	19	13827
  BCL11A-10049	-	AGAAAAUGGGGGGGUAGGGA	20	13828
  BCL11A-11685	-	AAGAAAAUGGGGGGGUAGGGA	21	13829
  BCL11A-11686	-	UAAGAAAAUGGGGGGGUAGGGA	22	13830
  BCL11A-11687	-	GUAAGAAAAUGGGGGGGUAGGGA	23	13831
  BCL11A-11688	-	CGUAAGAAAAUGGGGGGGUAGGGA	24	13832
  BCL11A-11689	-	AAGGGGCCCCCGGCGCUC	18	13833
  BCL11A-11690	-	AAAGGGGCCCCCGGCGCUC	19	13834
  BCL11A-11691	-	GAAAGGGGCCCCCGGCGCUC	20	13835
  BCL11A-11692	-	GGAAAGGGGCCCCCGGCGCUC	21	13836
  BCL11A-11693	-	UGGAAAGGGGCCCCCGGCGCUC	22	13837
  BCL11A-11694	-	GUGGAAAGGGGCCCCCGGCGCUC	23	13838
  BCL11A-11695	-	UGUGGAAAGGGGCCCCCGGCGCUC	24	13839
  BCL11A-11696	-	CUUUUGUUCCGGCCAGAG	18	13840
  BCL11A-11697	-	CCUUUUGUUCCGGCCAGAG	19	13841
  BCL11A-11698	-	GCCUUUUGUUCCGGCCAGAG	20	13842
  BCL11A-11699	-	CGCCUUUUGUUCCGGCCAGAG	21	13843
  BCL11A-11700	-	CCGCCUUUUGUUCCGGCCAGAG	22	13844
  BCL11A-11701	-	GCCGCCUUUUGUUCCGGCCAGAG	23	13845
  BCL11A-11702	-	UGCCGCCUUUUGUUCCGGCCAGAG	24	13846
  BCL11A-11703	-	GUGGGUGUGCGUACGGAG	18	13847
  BCL11A-11704	-	AGUGGGUGUGCGUACGGAG	19	13848
  BCL11A-11705	-	AAGUGGGUGUGCGUACGGAG	20	13849
  BCL11A-11706	-	GAAGUGGGUGUGCGUACGGAG	21	13850
  BCL11A-11707	-	GGAAGUGGGUGUGCGUACGGAG	22	13851
  BCL11A-11708	-	GGGAAGUGGGUGUGCGUACGGAG	23	13852
  BCL11A-11709	-	GGGGAAGUGGGUGUGCGUACGGAG	24	13853
  BCL11A-11710	-	CCGGCGCUCCUGAGUCCG	18	13854
  BCL11A-11711	-	CCCGGCGCUCCUGAGUCCG	19	13855
  BCL11A-10172	-	CCCCGGCGCUCCUGAGUCCG	20	13856
  BCL11A-11712	-	CCCCCGGCGCUCCUGAGUCCG	21	13857
  BCL11A-11713	-	GCCCCCGGCGCUCCUGAGUCCG	22	13858
  BCL11A-11714	-	GGCCCCCGGCGCUCCUGAGUCCG	23	13859
  BCL11A-11715	-	GGGCCCCCGGCGCUCCUGAGUCCG	24	13860
  BCL11A-11716	-	CAGCCCUCCAAACUUAGG	18	13861
  BCL11A-11717	-	GCAGCCCUCCAAACUUAGG	19	13862
  BCL11A-11718	-	CGCAGCCCUCCAAACUUAGG	20	13863
  BCL11A-11719	-	CCGCAGCCCUCCAAACUUAGG	21	13864
  BCL11A-11720	-	CCCGCAGCCCUCCAAACUUAGG	22	13865
  BCL11A-11721	-	ACCCGCAGCCCUCCAAACUUAGG	23	13866
  BCL11A-11722	-	GACCCGCAGCCCUCCAAACUUAGG	24	13867
  BCL11A-11723	-	CUCACCGUAAGAAAAUGG	18	13868
  BCL11A-11724	-	ACUCACCGUAAGAAAAUGG	19	13869
  BCL11A-10214	-	CACUCACCGUAAGAAAAUGG	20	13870
  BCL11A-11725	-	CCACUCACCGUAAGAAAAUGG	21	13871
  BCL11A-11726	-	CCCACUCACCGUAAGAAAAUGG	22	13872
  BCL11A-11727	-	UCCCACUCACCGUAAGAAAAUGG	23	13873
  BCL11A-11728	-	UUCCCACUCACCGUAAGAAAAUGG	24	13874
  BCL11A-11729	-	GAGGCUCAGCUCUCAACU	18	13875
  BCL11A-11730	-	GGAGGCUCAGCUCUCAACU	19	13876
  BCL11A-11731	-	UGGAGGCUCAGCUCUCAACU	20	13877
  BCL11A-11732	-	UUGGAGGCUCAGCUCUCAACU	21	13878
  BCL11A-11733	-	CUUGGAGGCUCAGCUCUCAACU	22	13879
  BCL11A-11734	-	ACUUGGAGGCUCAGCUCUCAACU	23	13880
  BCL11A-11735	-	AACUUGGAGGCUCAGCUCUCAACU	24	13881
  BCL11A-11736	-	CAACUCACAUGCAAACCU	18	13882
  BCL11A-11737	-	ACAACUCACAUGCAAACCU	19	13883
  BCL11A-10235	-	AACAACUCACAUGCAAACCU	20	13884
  BCL11A-11738	-	GAACAACUCACAUGCAAACCU	21	13885
  BCL11A-11739	-	CGAACAACUCACAUGCAAACCU	22	13886
  BCL11A-11740	-	GCGAACAACUCACAUGCAAACCU	23	13887
  BCL11A-11741	-	UGCGAACAACUCACAUGCAAACCU	24	13888
  BCL11A-10351	-	UUGAAUAAUCUUUCAUUU	18	13889
  BCL11A-10352	-	UUUGAAUAAUCUUUCAUUU	19	13890
  BCL11A-10353	-	UUUUGAAUAAUCUUUCAUUU	20	13891
  BCL11A-10354	-	UUUUUGAAUAAUCUUUCAUUU	21	13892
  BCL11A-10355	-	UUUUUUGAAUAAUCUUUCAUUU	22	13893
  BCL11A-10356	-	CUUUUUUGAAUAAUCUUUCAUUU	23	13894
  BCL11A-10357	-	UCUUUUUUGAAUAAUCUUUCAUUU	24	13895
  BCL11A-11742	-	GCUCUAUUUUUUUCUUUU	18	13896
  BCL11A-11743	-	CGCUCUAUUUUUUUCUUUU	19	13897
  BCL11A-11744	-	UCGCUCUAUUUUUUUCUUUU	20	13898
  BCL11A-11745	-	CUCGCUCUAUUUUUUUCUUUU	21	13899
  BCL11A-11746	-	UCUCGCUCUAUUUUUUUCUUUU	22	13900
  BCL11A-11747	-	CUCUCGCUCUAUUUUUUUCUUUU	23	13901
  BCL11A-11748	-	ACUCUCGCUCUAUUUUUUUCUUUU	24	13902

• Table 19E 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 1 kb 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 BCL11A gene (e.g., reduce or eliminate BCL11A gene expression, BCL13A protein function, or the level of BCL11A protein). One or more gRNA may be used to target an eiCas9 to the promoter region of the BCL11A gene.

• TABLE 19E
  5th Tier

  			Target
  	DNA		Site	SEQ
  gRNA Name	Strand	Targeting Domain	Length	ID NO:
  BCL11A-11749	+	AUUCAAAAAAGAAAAAAA	18	13903
  BCL11A-11750	+	UAUUCAAAAAAGAAAAAAA	19	13904
  BCL11A-11751	+	UUAUUCAAAAAAGAAAAAAA	20	13905
  BCL11A-11752	+	AUUAUUCAAAAAAGAAAAAAA	21	13906
  BCL11A-11753	+	GAUUAUUCAAAAAAGAAAAAAA	22	13907
  BCL11A-11754	+	AGAUUAUUCAAAAAAGAAAAAAA	23	13908
  BCL11A-11755	+	AAGAUUAUUCAAAAAAGAAAAAAA	24	13909
  BCL11A-11756	+	AUGAAAGAUUAUUCAAAA	18	13910
  BCL11A-11757	+	AAUGAAAGAUUAUUCAAAA	19	13911
  BCL11A-11758	+	AAAUGAAAGAUUAUUCAAAA	20	13912
  BCL11A-11759	+	AAAAUGAAAGAUUAUUCAAAA	21	13913
  BCL11A-11760	+	UAAAAUGAAAGAUUAUUCAAAA	22	13914
  BCL11A-11761	+	CUAAAAUGAAAGAUUAUUCAAAA	23	13915
  BCL11A-11762	+	UCUAAAAUGAAAGAUUAUUCAAAA	24	13916
  BCL11A-11763	+	UGCAUUCCUUUUCGAAAA	18	13917
  BCL11A-11764	+	UUGCAUUCCUUUUCGAAAA	19	13918
  BCL11A-11765	+	AUUGCAUUCCUUUUCGAAAA	20	13919
  BCL11A-11766	+	CAUUGCAUUCCUUUUCGAAAA	21	13920
  BCL11A-11767	+	UCAUUGCAUUCCUUUUCGAAAA	22	13921
  BCL11A-11768	+	AUCAUUGCAUUCCUUUUCGAAAA	23	13922
  BCL11A-11769	+	AAUCAUUGCAUUCCUUUUCGAAAA	24	13923
  BCL11A-11770	+	GCGGCGGAAAGGAGGAAA	18	13924
  BCL11A-11771	+	AGCGGCGGAAAGGAGGAAA	19	13925
  BCL11A-11772	+	AAGCGGCGGAAAGGAGGAAA	20	13926
  BCL11A-11773	+	AAAGCGGCGGAAAGGAGGAAA	21	13927
  BCL11A-11774	+	UAAAGCGGCGGAAAGGAGGAAA	22	13928
  BCL11A-11775	+	AUAAAGCGGCGGAAAGGAGGAAA	23	13929
  BCL11A-11776	+	AAUAAAGCGGCGGAAAGGAGGAAA	24	13930
  BCL11A-11777	+	GCCCGCGCGGCCUGGAAA	18	13931
  BCL11A-11778	+	AGCCCGCGCGGCCUGGAAA	19	13932
  BCL11A-11779	+	GAGCCCGCGCGGCCUGGAAA	20	13933
  BCL11A-11780	+	GGAGCCCGCGCGGCCUGGAAA	21	13934
  BCL11A-11781	+	AGGAGCCCGCGCGGCCUGGAAA	22	13935
  BCL11A-11782	+	CAGGAGCCCGCGCGGCCUGGAAA	23	13936
  BCL11A-11783	+	CCAGGAGCCCGCGCGGCCUGGAAA	24	13937
  BCL11A-10371	+	ACACACGCGGACUCUAAA	18	13938
  BCL11A-10372	+	CACACACGCGGACUCUAAA	19	13939
  BCL11A-10373	+	CCACACACGCGGACUCUAAA	20	13940
  BCL11A-10374	+	CCCACACACGCGGACUCUAAA	21	13941
  BCL11A-10375	+	CCCCACACACGCGGACUCUAAA	22	13942
  BCL11A-10376	+	CCCCCACACACGCGGACUCUAAA	23	13943
  BCL11A-10377	+	CCCCCCACACACGCGGACUCUAAA	24	13944
  BCL11A-11784	+	AUUGCAUUCCUUUUCGAA	18	13945
  BCL11A-11785	+	CAUUGCAUUCCUUUUCGAA	19	13946
  BCL11A-11786	+	UCAUUGCAUUCCUUUUCGAA	20	13947
  BCL11A-11787	+	AUCAUUGCAUUCCUUUUCGAA	21	13948
  BCL11A-11788	+	AAUCAUUGCAUUCCUUUUCGAA	22	13949
  BCL11A-11789	+	GAAUCAUUGCAUUCCUUUUCGAA	23	13950
  BCL11A-11790	+	GGAAUCAUUGCAUUCCUUUUCGAA	24	13951
  BCL11A-11791	+	AGAAAUAAAGCGGCGGAA	18	13952
  BCL11A-11792	+	GAGAAAUAAAGCGGCGGAA	19	13953
  BCL11A-10031	+	AGAGAAAUAAAGCGGCGGAA	20	13954
  BCL11A-11793	+	AAGAGAAAUAAAGCGGCGGAA	21	13955
  BCL11A-11794	+	AAAGAGAAAUAAAGCGGCGGAA	22	13956
  BCL11A-11795	+	AAAAGAGAAAUAAAGCGGCGGAA	23	13957
  BCL11A-11796	+	GAAAAGAGAAAUAAAGCGGCGGAA	24	13958
  BCL11A-11797	+	CCCGAGGAGAGGACAGCA	18	13959
  BCL11A-11798	+	GCCCGAGGAGAGGACAGCA	19	13960
  BCL11A-11799	+	UGCCCGAGGAGAGGACAGCA	20	13961
  BCL11A-11800	+	UUGCCCGAGGAGAGGACAGCA	21	13962
  BCL11A-11801	+	UUUGCCCGAGGAGAGGACAGCA	22	13963
  BCL11A-11802	+	CUUUGCCCGAGGAGAGGACAGCA	23	13964
  BCL11A-11803	+	ACUUUGCCCGAGGAGAGGACAGCA	24	13965
  BCL11A-11804	+	CCAAGUUACAGCUCCGCA	18	13966
  BCL11A-11805	+	UCCAAGUUACAGCUCCGCA	19	13967
  BCL11A-11806	+	CUCCAAGUUACAGCUCCGCA	20	13968
  BCL11A-11807	+	CCUCCAAGUUACAGCUCCGCA	21	13969
  BCL11A-11808	+	GCCUCCAAGUUACAGCUCCGCA	22	13970
  BCL11A-11809	+	AGCCUCCAAGUUACAGCUCCGCA	23	13971
  BCL11A-11810	+	GAGCCUCCAAGUUACAGCUCCGCA	24	13972
  BCL11A-11811	+	GAGCCGGCACAAAAGGCA	18	13973
  BCL11A-11812	+	GGAGCCGGCACAAAAGGCA	19	13974
  BCL11A-11813	+	AGGAGCCGGCACAAAAGGCA	20	13975
  BCL11A-11814	+	GAGGAGCCGGCACAAAAGGCA	21	13976
  BCL11A-11815	+	CGAGGAGCCGGCACAAAAGGCA	22	13977
  BCL11A-11816	+	GCGAGGAGCCGGCACAAAAGGCA	23	13978
  BCL11A-11817	+	CGCGAGGAGCCGGCACAAAAGGCA	24	13979
  BCL11A-11818	+	AAAUAGAGCGAGAGUGCA	18	13980
  BCL11A-11819	+	AAAAUAGAGCGAGAGUGCA	19	13981
  BCL11A-11820	+	AAAAAUAGAGCGAGAGUGCA	20	13982
  BCL11A-11821	+	AAAAAAUAGAGCGAGAGUGCA	21	13983
  BCL11A-11822	+	AAAAAAAUAGAGCGAGAGUGCA	22	13984
  BCL11A-11823	+	GAAAAAAAUAGAGCGAGAGUGCA	23	13985
  BCL11A-11824	+	AGAAAAAAAUAGAGCGAGAGUGCA	24	13986
  BCL11A-11825	+	CCGCGCGGCCUGGAAAGA	18	13987
  BCL11A-11826	+	CCCGCGCGGCCUGGAAAGA	19	13988
  BCL11A-10040	+	GCCCGCGCGGCCUGGAAAGA	20	13989
  BCL11A-11827	+	AGCCCGCGCGGCCUGGAAAGA	21	13990
  BCL11A-11828	+	GAGCCCGCGCGGCCUGGAAAGA	22	13991
  BCL11A-11829	+	GGAGCCCGCGCGGCCUGGAAAGA	23	13992
  BCL11A-11830	+	AGGAGCCCGCGCGGCCUGGAAAGA	24	13993
  BCL11A-11831	+	AAAAAAGAAAAAAAUAGA	18	13994
  BCL11A-11832	+	CAAAAAAGAAAAAAAUAGA	19	13995
  BCL11A-11833	+	UCAAAAAAGAAAAAAAUAGA	20	13996
  BCL11A-11834	+	UUCAAAAAAGAAAAAAAUAGA	21	13997
  BCL11A-11835	+	AUUCAAAAAAGAAAAAAAUAGA	22	13998
  BCL11A-11836	+	UAUUCAAAAAAGAAAAAAAUAGA	23	13999
  BCL11A-11837	+	UUAUUCAAAAAAGAAAAAAAUAGA	24	14000
  BCL11A-11838	+	CAGCUCCGCAGCGGGCGA	18	14001
  BCL11A-11839	+	ACAGCUCCGCAGCGGGCGA	19	14002
  BCL11A-10044	+	UACAGCUCCGCAGCGGGCGA	20	14003
  BCL11A-11840	+	UUACAGCUCCGCAGCGGGCGA	21	14004
  BCL11A-11841	+	GUUACAGCUCCGCAGCGGGCGA	22	14005
  BCL11A-11842	+	AGUUACAGCUCCGCAGCGGGCGA	23	14006
  BCL11A-11843	+	AAGUUACAGCUCCGCAGCGGGCGA	24	14007
  BCL11A-11844	+	GGAAACUUUGCCCGAGGA	18	14008
  BCL11A-11845	+	GGGAAACUUUGCCCGAGGA	19	14009
  BCL11A-11846	+	CGGGAAACUUUGCCCGAGGA	20	14010
  BCL11A-11847	+	UCGGGAAACUUUGCCCGAGGA	21	14011
  BCL11A-11848	+	CUCGGGAAACUUUGCCCGAGGA	22	14012
  BCL11A-11849	+	GCUCGGGAAACUUUGCCCGAGGA	23	14013
  BCL11A-11850	+	CGCUCGGGAAACUUUGCCCGAGGA	24	14014
  BCL11A-11851	+	AAGCGGCGGAAAGGAGGA	18	14015
  BCL11A-11852	+	AAAGCGGCGGAAAGGAGGA	19	14016
  BCL11A-11853	+	UAAAGCGGCGGAAAGGAGGA	20	14017
  BCL11A-11854	+	AUAAAGCGGCGGAAAGGAGGA	21	14018
  BCL11A-11855	+	AAUAAAGCGGCGGAAAGGAGGA	22	14019
  BCL11A-11856	+	AAAUAAAGCGGCGGAAAGGAGGA	23	14020
  BCL11A-11857	+	GAAAUAAAGCGGCGGAAAGGAGGA	24	14021
  BCL11A-11858	+	GAGAAAUAAAGCGGCGGA	18	14022
  BCL11A-11859	+	AGAGAAAUAAAGCGGCGGA	19	14023
  BCL11A-11860	+	AAGAGAAAUAAAGCGGCGGA	20	14024
  BCL11A-11861	+	AAAGAGAAAUAAAGCGGCGGA	21	14025
  BCL11A-11862	+	AAAAGAGAAAUAAAGCGGCGGA	22	14026
  BCL11A-11863	+	GAAAAGAGAAAUAAAGCGGCGGA	23	14027
  BCL11A-11864	+	CGAAAAGAGAAAUAAAGCGGCGGA	24	14028
  BCL11A-11865	+	UGGGGAAGCGCGGGCGGA	18	14029
  BCL11A-11866	+	CUGGGGAAGCGCGGGCGGA	19	14030
  BCL11A-10048	+	GCUGGGGAAGCGCGGGCGGA	20	14031
  BCL11A-11867	+	GGCUGGGGAAGCGCGGGCGGA	21	14032
  BCL11A-11868	+	GGGCUGGGGAAGCGCGGGCGGA	22	14033
  BCL11A-11869	+	CGGGCUGGGGAAGCGCGGGCGGA	23	14034
  BCL11A-11870	+	CCGGGCUGGGGAAGCGCGGGCGGA	24	14035
  BCL11A-11871	+	CCAAGGCCGAGCCAGGGA	18	14036
  BCL11A-11872	+	CCCAAGGCCGAGCCAGGGA	19	14037
  BCL11A-11873	+	CCCCAAGGCCGAGCCAGGGA	20	14038
  BCL11A-11874	+	CCCCCAAGGCCGAGCCAGGGA	21	14039
  BCL11A-11875	+	GCCCCCAAGGCCGAGCCAGGGA	22	14040
  BCL11A-11876	+	CGCCCCCAAGGCCGAGCCAGGGA	23	14041
  BCL11A-11877	+	GCGCCCCCAAGGCCGAGCCAGGGA	24	14042
  BCL11A-11878	+	CGGCCUGGAAAGAGGGGA	18	14043
  BCL11A-11879	+	GCGGCCUGGAAAGAGGGGA	19	14044
  BCL11A-11880	+	CGCGGCCUGGAAAGAGGGGA	20	14045
  BCL11A-11881	+	GCGCGGCCUGGAAAGAGGGGA	21	14046
  BCL11A-11882	+	CGCGCGGCCUGGAAAGAGGGGA	22	14047
  BCL11A-11883	+	CCGCGCGGCCUGGAAAGAGGGGA	23	14048
  BCL11A-11884	+	CCCGCGCGGCCUGGAAAGAGGGGA	24	14049
  BCL11A-11885	+	UGGCGGGGCGGGGGGGGA	18	14050
  BCL11A-11886	+	CUGGCGGGGCGGGGGGGGA	19	14051
  BCL11A-11887	+	ACUGGCGGGGCGGGGGGGGA	20	14052
  BCL11A-11888	+	AACUGGCGGGGCGGGGGGGGA	21	14053
  BCL11A-11889	+	AAACUGGCGGGGCGGGGGGGGA	22	14054
  BCL11A-11890	+	AAAACUGGCGGGGCGGGGGGGGA	23	14055
  BCL11A-11891	+	CAAAACUGGCGGGGCGGGGGGGGA	24	14056
  BCL11A-11892	+	GGGCGAGGGGAGGUGGGA	18	14057
  BCL11A-11893	+	CGGGCGAGGGGAGGUGGGA	19	14058
  BCL11A-10052	+	GCGGGCGAGGGGAGGUGGGA	20	14059
  BCL11A-11894	+	AGCGGGCGAGGGGAGGUGGGA	21	14060
  BCL11A-11895	+	CAGCGGGCGAGGGGAGGUGGGA	22	14061
  BCL11A-11896	+	GCAGCGGGCGAGGGGAGGUGGGA	23	14062
  BCL11A-11897	+	CGCAGCGGGCGAGGGGAGGUGGGA	24	14063
  BCL11A-11898	+	GAGCCCGCGCGGCCUGGA	18	14064
  BCL11A-11899	+	GGAGCCCGCGCGGCCUGGA	19	14065
  BCL11A-11900	+	AGGAGCCCGCGCGGCCUGGA	20	14066
  BCL11A-11901	+	CAGGAGCCCGCGCGGCCUGGA	21	14067
  BCL11A-11902	+	CCAGGAGCCCGCGCGGCCUGGA	22	14068
  BCL11A-11903	+	UCCAGGAGCCCGCGCGGCCUGGA	23	14069
  BCL11A-11904	+	CUCCAGGAGCCCGCGCGGCCUGGA	24	14070
  BCL11A-11905	+	CCCAUUUUCUUACGGUGA	18	14071
  BCL11A-11906	+	CCCCAUUUUCUUACGGUGA	19	14072
  BCL11A-11907	+	CCCCCAUUUUCUUACGGUGA	20	14073
  BCL11A-11908	+	CCCCCCAUUUUCUUACGGUGA	21	14074
  BCL11A-11909	+	CCCCCCCAUUUUCUUACGGUGA	22	14075
  BCL11A-11910	+	ACCCCCCCAUUUUCUUACGGUGA	23	14076
  BCL11A-11911	+	UACCCCCCCAUUUUCUUACGGUGA	24	14077
  BCL11A-11912	+	GAGGGAGCGCACGGCAAC	18	14078
  BCL11A-11913	+	GGAGGGAGCGCACGGCAAC	19	14079
  BCL11A-11914	+	GGGAGGGAGCGCACGGCAAC	20	14080
  BCL11A-11915	+	UGGGAGGGAGCGCACGGCAAC	21	14081
  BCL11A-11916	+	GUGGGAGGGAGCGCACGGCAAC	22	14082
  BCL11A-11917	+	GGUGGGAGGGAGCGCACGGCAAC	23	14083
  BCL11A-11918	+	AGGUGGGAGGGAGCGCACGGCAAC	24	14084
  BCL11A-10612	+	CUGCUCCCCCCCACACAC	18	14085
  BCL11A-10613	+	CCUGCUCCCCCCCACACAC	19	14086
  BCL11A-10614	+	CCCUGCUCCCCCCCACACAC	20	14087
  BCL11A-10615	+	GCCCUGCUCCCCCCCACACAC	21	14088
  BCL11A-10616	+	CGCCCUGCUCCCCCCCACACAC	22	14089
  BCL11A-10617	+	GCGCCCUGCUCCCCCCCACACAC	23	14090
  BCL11A-10618	+	UGCGCCCUGCUCCCCCCCACACAC	24	14091
  BCL11A-11919	+	AAUAGAGCGAGAGUGCAC	18	14092
  BCL11A-11920	+	AAAUAGAGCGAGAGUGCAC	19	14093
  BCL11A-10059	+	AAAAUAGAGCGAGAGUGCAC	20	14094
  BCL11A-11921	+	AAAAAUAGAGCGAGAGUGCAC	21	14095
  BCL11A-11922	+	AAAAAAUAGAGCGAGAGUGCAC	22	14096
  BCL11A-11923	+	AAAAAAAUAGAGCGAGAGUGCAC	23	14097
  BCL11A-11924	+	GAAAAAAAUAGAGCGAGAGUGCAC	24	14098
  BCL11A-11925	+	ACAGCAAAGAAAAAUCAC	18	14099
  BCL11A-11926	+	GACAGCAAAGAAAAAUCAC	19	14100
  BCL11A-11927	+	GGACAGCAAAGAAAAAUCAC	20	14101
  BCL11A-11928	+	AGGACAGCAAAGAAAAAUCAC	21	14102
  BCL11A-11929	+	GAGGACAGCAAAGAAAAAUCAC	22	14103
  BCL11A-11930	+	AGAGGACAGCAAAGAAAAAUCAC	23	14104
  BCL11A-11931	+	GAGAGGACAGCAAAGAAAAAUCAC	24	14105
  BCL11A-11932	+	CAAGGCCGAGCCAGGGAC	18	14106
  BCL11A-11933	+	CCAAGGCCGAGCCAGGGAC	19	14107
  BCL11A-10063	+	CCCAAGGCCGAGCCAGGGAC	20	14108
  BCL11A-11934	+	CCCCAAGGCCGAGCCAGGGAC	21	14109
  BCL11A-11935	+	CCCCCAAGGCCGAGCCAGGGAC	22	14110
  BCL11A-11936	+	GCCCCCAAGGCCGAGCCAGGGAC	23	14111
  BCL11A-11937	+	CGCCCCCAAGGCCGAGCCAGGGAC	24	14112
  BCL11A-11938	+	GGCCUGGAAAGAGGGGAC	18	14113
  BCL11A-11939	+	CGGCCUGGAAAGAGGGGAC	19	14114
  BCL11A-10064	+	GCGGCCUGGAAAGAGGGGAC	20	14115
  BCL11A-11940	+	CGCGGCCUGGAAAGAGGGGAC	21	14116
  BCL11A-11941	+	GCGCGGCCUGGAAAGAGGGGAC	22	14117
  BCL11A-11942	+	CGCGCGGCCUGGAAAGAGGGGAC	23	14118
  BCL11A-11943	+	CCGCGCGGCCUGGAAAGAGGGGAC	24	14119
  BCL11A-11944	+	AUAGAGCGAGAGUGCACC	18	14120
  BCL11A-11945	+	AAUAGAGCGAGAGUGCACC	19	14121
  BCL11A-10067	+	AAAUAGAGCGAGAGUGCACC	20	14122
  BCL11A-11946	+	AAAAUAGAGCGAGAGUGCACC	21	14123
  BCL11A-11947	+	AAAAAUAGAGCGAGAGUGCACC	22	14124
  BCL11A-11948	+	AAAAAAUAGAGCGAGAGUGCACC	23	14125
  BCL11A-11949	+	AAAAAAAUAGAGCGAGAGUGCACC	24	14126
  BCL11A-11950	+	AAGGCCGAGCCAGGGACC	18	14127
  BCL11A-11951	+	CAAGGCCGAGCCAGGGACC	19	14128
  BCL11A-10068	+	CCAAGGCCGAGCCAGGGACC	20	14129
  BCL11A-11952	+	CCCAAGGCCGAGCCAGGGACC	21	14130
  BCL11A-11953	+	CCCCAAGGCCGAGCCAGGGACC	22	14131
  BCL11A-11954	+	CCCCCAAGGCCGAGCCAGGGACC	23	14132
  BCL11A-11955	+	GCCCCCAAGGCCGAGCCAGGGACC	24	14133
  BCL11A-11956	+	GCCUGGAAAGAGGGGACC	18	14134
  BCL11A-11957	+	GGCCUGGAAAGAGGGGACC	19	14135
  BCL11A-10069	+	CGGCCUGGAAAGAGGGGACC	20	14136
  BCL11A-11958	+	GCGGCCUGGAAAGAGGGGACC	21	14137
  BCL11A-11959	+	CGCGGCCUGGAAAGAGGGGACC	22	14138
  BCL11A-11960	+	GCGCGGCCUGGAAAGAGGGGACC	23	14139
  BCL11A-11961	+	CGCGCGGCCUGGAAAGAGGGGACC	24	14140
  BCL11A-11962	+	CCCGCUGCACACUUGACC	18	14141
  BCL11A-11963	+	UCCCGCUGCACACUUGACC	19	14142
  BCL11A-11964	+	CUCCCGCUGCACACUUGACC	20	14143
  BCL11A-11965	+	CCUCCCGCUGCACACUUGACC	21	14144
  BCL11A-11966	+	UCCUCCCGCUGCACACUUGACC	22	14145
  BCL11A-11967	+	UUCCUCCCGCUGCACACUUGACC	23	14146
  BCL11A-11968	+	UUUCCUCCCGCUGCACACUUGACC	24	14147
  BCL11A-11969	+	CGGCGCAGGCCGGGGCCC	18	14148
  BCL11A-11970	+	GCGGCGCAGGCCGGGGCCC	19	14149
  BCL11A-11971	+	GGCGGCGCAGGCCGGGGCCC	20	14150
  BCL11A-11972	+	AGGCGGCGCAGGCCGGGGCCC	21	14151
  BCL11A-11973	+	CAGGCGGCGCAGGCCGGGGCCC	22	14152
  BCL11A-11974	+	GCAGGCGGCGCAGGCCGGGGCCC	23	14153
  BCL11A-11975	+	GGCAGGCGGCGCAGGCCGGGGCCC	24	14154
  BCL11A-11976	+	GCUCGGGAAACUUUGCCC	18	14155
  BCL11A-11977	+	CGCUCGGGAAACUUUGCCC	19	14156
  BCL11A-11978	+	GCGCUCGGGAAACUUUGCCC	20	14157
  BCL11A-11979	+	UGCGCUCGGGAAACUUUGCCC	21	14158
  BCL11A-11980	+	CUGCGCUCGGGAAACUUUGCCC	22	14159
  BCL11A-11981	+	GCUGCGCUCGGGAAACUUUGCCC	23	14160
  BCL11A-11982	+	GGCUGCGCUCGGGAAACUUUGCCC	24	14161
  BCL11A-11983	+	UCUCACCUCUUUUCUCCC	18	14162
  BCL11A-11984	+	GUCUCACCUCUUUUCUCCC	19	14163
  BCL11A-10081	+	AGUCUCACCUCUUUUCUCCC	20	14164
  BCL11A-11985	+	CAGUCUCACCUCUUUUCUCCC	21	14165
  BCL11A-11986	+	CCAGUCUCACCUCUUUUCUCCC	22	14166
  BCL11A-11987	+	GCCAGUCUCACCUCUUUUCUCCC	23	14167
  BCL11A-11988	+	AGCCAGUCUCACCUCUUUUCUCCC	24	14168
  BCL11A-11989	+	GGGGCCGAAGUAAAAGCC	18	14169
  BCL11A-11990	+	AGGGGCCGAAGUAAAAGCC	19	14170
  BCL11A-11991	+	CAGGGGCCGAAGUAAAAGCC	20	14171
  BCL11A-11992	+	CCAGGGGCCGAAGUAAAAGCC	21	14172
  BCL11A-11993	+	GCCAGGGGCCGAAGUAAAAGCC	22	14173
  BCL11A-11994	+	CGCCAGGGGCCGAAGUAAAAGCC	23	14174
  BCL11A-11995	+	ACGCCAGGGGCCGAAGUAAAAGCC	24	14175
  BCL11A-11996	+	CACCGGGAGGCUGCAGCC	18	14176
  BCL11A-11997	+	GCACCGGGAGGCUGCAGCC	19	14177
  BCL11A-11998	+	UGCACCGGGAGGCUGCAGCC	20	14178
  BCL11A-11999	+	GUGCACCGGGAGGCUGCAGCC	21	14179
  BCL11A-12000	+	AGUGCACCGGGAGGCUGCAGCC	22	14180
  BCL11A-12001	+	GAGUGCACCGGGAGGCUGCAGCC	23	14181
  BCL11A-12002	+	AGAGUGCACCGGGAGGCUGCAGCC	24	14182
  BCL11A-12003	+	CGCCCCCAAGGCCGAGCC	18	14183
  BCL11A-12004	+	GCGCCCCCAAGGCCGAGCC	19	14184
  BCL11A-10085	+	GGCGCCCCCAAGGCCGAGCC	20	14185
  BCL11A-12005	+	GGGCGCCCCCAAGGCCGAGCC	21	14186
  BCL11A-12006	+	AGGGCGCCCCCAAGGCCGAGCC	22	14187
  BCL11A-12007	+	GAGGGCGCCCCCAAGGCCGAGCC	23	14188
  BCL11A-12008	+	CGAGGGCGCCCCCAAGGCCGAGCC	24	14189
  BCL11A-12009	+	UCCCCGCGUGUGGACGCC	18	14190
  BCL11A-12010	+	CUCCCCGCGUGUGGACGCC	19	14191
  BCL11A-10086	+	GCUCCCCGCGUGUGGACGCC	20	14192
  BCL11A-12011	+	CGCUCCCCGCGUGUGGACGCC	21	14193
  BCL11A-12012	+	UCGCUCCCCGCGUGUGGACGCC	22	14194
  BCL11A-12013	+	CUCGCUCCCCGCGUGUGGACGCC	23	14195
  BCL11A-12014	+	GCUCGCUCCCCGCGUGUGGACGCC	24	14196
  BCL11A-12015	+	CGCGGACUCAGGAGCGCC	18	14197
  BCL11A-12016	+	CCGCGGACUCAGGAGCGCC	19	14198
  BCL11A-10087	+	UCCGCGGACUCAGGAGCGCC	20	14199
  BCL11A-12017	+	CUCCGCGGACUCAGGAGCGCC	21	14200
  BCL11A-12018	+	ACUCCGCGGACUCAGGAGCGCC	22	14201
  BCL11A-12019	+	GACUCCGCGGACUCAGGAGCGCC	23	14202
  BCL11A-12020	+	CGACUCCGCGGACUCAGGAGCGCC	24	14203
  BCL11A-12021	+	CCAGGAGCCCGCGCGGCC	18	14204
  BCL11A-12022	+	UCCAGGAGCCCGCGCGGCC	19	14205
  BCL11A-10089	+	CUCCAGGAGCCCGCGCGGCC	20	14206
  BCL11A-12023	+	UCUCCAGGAGCCCGCGCGGCC	21	14207
  BCL11A-12024	+	GUCUCCAGGAGCCCGCGCGGCC	22	14208
  BCL11A-12025	+	AGUCUCCAGGAGCCCGCGCGGCC	23	14209
  BCL11A-12026	+	AAGUCUCCAGGAGCCCGCGCGGCC	24	14210
  BCL11A-12027	+	GGCCCCUCUCCCGACUCC	18	14211
  BCL11A-12028	+	CGGCCCCUCUCCCGACUCC	19	14212
  BCL11A-12029	+	GCGGCCCCUCUCCCGACUCC	20	14213
  BCL11A-12030	+	CGCGGCCCCUCUCCCGACUCC	21	14214
  BCL11A-12031	+	CCGCGGCCCCUCUCCCGACUCC	22	14215
  BCL11A-12032	+	GCCGCGGCCCCUCUCCCGACUCC	23	14216
  BCL11A-12033	+	CGCCGCGGCCCCUCUCCCGACUCC	24	14217
  BCL11A-12034	+	GGCAGCGCCCAAGUCUCC	18	14218
  BCL11A-12035	+	GGGCAGCGCCCAAGUCUCC	19	14219
  BCL11A-10093	+	AGGGCAGCGCCCAAGUCUCC	20	14220
  BCL11A-12036	+	AAGGGCAGCGCCCAAGUCUCC	21	14221
  BCL11A-12037	+	GAAGGGCAGCGCCCAAGUCUCC	22	14222
  BCL11A-12038	+	GGAAGGGCAGCGCCCAAGUCUCC	23	14223
  BCL11A-12039	+	CGGAAGGGCAGCGCCCAAGUCUCC	24	14224
  BCL11A-12040	+	GUCUCACCUCUUUUCUCC	18	14225
  BCL11A-12041	+	AGUCUCACCUCUUUUCUCC	19	14226
  BCL11A-12042	+	CAGUCUCACCUCUUUUCUCC	20	14227
  BCL11A-12043	+	CCAGUCUCACCUCUUUUCUCC	21	14228
  BCL11A-12044	+	GCCAGUCUCACCUCUUUUCUCC	22	14229
  BCL11A-12045	+	AGCCAGUCUCACCUCUUUUCUCC	23	14230
  BCL11A-12046	+	AAGCCAGUCUCACCUCUUUUCUCC	24	14231
  BCL11A-12047	+	CGGCGCGGGAGGGCAAGC	18	14232
  BCL11A-12048	+	GCGGCGCGGGAGGGCAAGC	19	14233
  BCL11A-12049	+	GGCGGCGCGGGAGGGCAAGC	20	14234
  BCL11A-12050	+	GCCCCGGGCUGGGGAAGC	18	14235
  BCL11A-12051	+	AGCCCCGGGCUGGGGAAGC	19	14236
  BCL11A-12052	+	CAGCCCCGGGCUGGGGAAGC	20	14237
  BCL11A-12053	+	GCAGCCCCGGGCUGGGGAAGC	21	14238
  BCL11A-12054	+	UGCAGCCCCGGGCUGGGGAAGC	22	14239
  BCL11A-12055	+	CUGCAGCCCCGGGCUGGGGAAGC	23	14240
  BCL11A-12056	+	GCUGCAGCCCCGGGCUGGGGAAGC	24	14241
  BCL11A-12057	+	GCGCCCCCAAGGCCGAGC	18	14242
  BCL11A-12058	+	GGCGCCCCCAAGGCCGAGC	19	14243
  BCL11A-12059	+	GGGCGCCCCCAAGGCCGAGC	20	14244
  BCL11A-12060	+	AGGGCGCCCCCAAGGCCGAGC	21	14245
  BCL11A-12061	+	GAGGGCGCCCCCAAGGCCGAGC	22	14246
  BCL11A-12062	+	CGAGGGCGCCCCCAAGGCCGAGC	23	14247
  BCL11A-12063	+	CCGAGGGCGCCCCCAAGGCCGAGC	24	14248
  BCL11A-12064	+	CUCCCCGCGUGUGGACGC	18	14249
  BCL11A-12065	+	GCUCCCCGCGUGUGGACGC	19	14250
  BCL11A-12066	+	CGCUCCCCGCGUGUGGACGC	20	14251
  BCL11A-12067	+	UCGCUCCCCGCGUGUGGACGC	21	14252
  BCL11A-12068	+	CUCGCUCCCCGCGUGUGGACGC	22	14253
  BCL11A-12069	+	GCUCGCUCCCCGCGUGUGGACGC	23	14254
  BCL11A-12070	+	CGCUCGCUCCCCGCGUGUGGACGC	24	14255
  BCL11A-12071	+	GCGCGGGAGGGCAAGCGC	18	14256
  BCL11A-12072	+	GGCGCGGGAGGGCAAGCGC	19	14257
  BCL11A-12073	+	CGGCGCGGGAGGGCAAGCGC	20	14258
  BCL11A-12074	+	CCGCGGACUCAGGAGCGC	18	14259
  BCL11A-12075	+	UCCGCGGACUCAGGAGCGC	19	14260
  BCL11A-10106	+	CUCCGCGGACUCAGGAGCGC	20	14261
  BCL11A-12076	+	ACUCCGCGGACUCAGGAGCGC	21	14262
  BCL11A-12077	+	GACUCCGCGGACUCAGGAGCGC	22	14263
  BCL11A-12078	+	CGACUCCGCGGACUCAGGAGCGC	23	14264
  BCL11A-12079	+	CCGACUCCGCGGACUCAGGAGCGC	24	14265
  BCL11A-12080	+	CCGAGCCCGCGGCUGCGC	18	14266
  BCL11A-12081	+	CCCGAGCCCGCGGCUGCGC	19	14267
  BCL11A-12082	+	CCCCGAGCCCGCGGCUGCGC	20	14268
  BCL11A-12083	+	GCCCCGAGCCCGCGGCUGCGC	21	14269
  BCL11A-12084	+	AGCCCCGAGCCCGCGGCUGCGC	22	14270
  BCL11A-12085	+	AAGCCCCGAGCCCGCGGCUGCGC	23	14271
  BCL11A-12086	+	AAAGCCCCGAGCCCGCGGCUGCGC	24	14272
  BCL11A-12087	+	GAGGCAGGCGGCGCAGGC	18	14273
  BCL11A-12088	+	AGAGGCAGGCGGCGCAGGC	19	14274
  BCL11A-10110	+	GAGAGGCAGGCGGCGCAGGC	20	14275
  BCL11A-12089	+	GGAGAGGCAGGCGGCGCAGGC	21	14276
  BCL11A-12090	+	GGGAGAGGCAGGCGGCGCAGGC	22	14277
  BCL11A-12091	+	GGGGAGAGGCAGGCGGCGCAGGC	23	14278
  BCL11A-12092	+	CGGGGAGAGGCAGGCGGCGCAGGC	24	14279
  BCL11A-12093	+	UCCAGGAGCCCGCGCGGC	18	14280
  BCL11A-12094	+	CUCCAGGAGCCCGCGCGGC	19	14281
  BCL11A-12095	+	UCUCCAGGAGCCCGCGCGGC	20	14282
  BCL11A-12096	+	GUCUCCAGGAGCCCGCGCGGC	21	14283
  BCL11A-12097	+	AGUCUCCAGGAGCCCGCGCGGC	22	14284
  BCL11A-12098	+	AAGUCUCCAGGAGCCCGCGCGGC	23	14285
  BCL11A-12099	+	CAAGUCUCCAGGAGCCCGCGCGGC	24	14286
  BCL11A-12100	+	GAGGCUGCAGCCCCGGGC	18	14287
  BCL11A-12101	+	GGAGGCUGCAGCCCCGGGC	19	14288
  BCL11A-10115	+	GGGAGGCUGCAGCCCCGGGC	20	14289
  BCL11A-12102	+	CGGGAGGCUGCAGCCCCGGGC	21	14290
  BCL11A-12103	+	CCGGGAGGCUGCAGCCCCGGGC	22	14291
  BCL11A-12104	+	ACCGGGAGGCUGCAGCCCCGGGC	23	14292
  BCL11A-12105	+	CACCGGGAGGCUGCAGCCCCGGGC	24	14293
  BCL11A-12106	+	UACAGCUCCGCAGCGGGC	18	14294
  BCL11A-12107	+	UUACAGCUCCGCAGCGGGC	19	14295
  BCL11A-12108	+	GUUACAGCUCCGCAGCGGGC	20	14296
  BCL11A-12109	+	AGUUACAGCUCCGCAGCGGGC	21	14297
  BCL11A-12110	+	AAGUUACAGCUCCGCAGCGGGC	22	14298
  BCL11A-12111	+	CAAGUUACAGCUCCGCAGCGGGC	23	14299
  BCL11A-12112	+	CCAAGUUACAGCUCCGCAGCGGGC	24	14300
  BCL11A-12113	+	GGCGGCGCAGGCCGGGGC	18	14301
  BCL11A-12114	+	AGGCGGCGCAGGCCGGGGC	19	14302
  BCL11A-12115	+	CAGGCGGCGCAGGCCGGGGC	20	14303
  BCL11A-12116	+	GCAGGCGGCGCAGGCCGGGGC	21	14304
  BCL11A-12117	+	GGCAGGCGGCGCAGGCCGGGGC	22	14305
  BCL11A-12118	+	AGGCAGGCGGCGCAGGCCGGGGC	23	14306
  BCL11A-12119	+	GAGGCAGGCGGCGCAGGCCGGGGC	24	14307
  BCL11A-12120	+	UUGCAAAACUGGCGGGGC	18	14308
  BCL11A-12121	+	UUUGCAAAACUGGCGGGGC	19	14309
  BCL11A-10116	+	UUUUGCAAAACUGGCGGGGC	20	14310
  BCL11A-12122	+	AUUUUGCAAAACUGGCGGGGC	21	14311
  BCL11A-12123	+	UAUUUUGCAAAACUGGCGGGGC	22	14312
  BCL11A-12124	+	UUAUUUUGCAAAACUGGCGGGGC	23	14313
  BCL11A-12125	+	AUUAUUUUGCAAAACUGGCGGGGC	24	14314
  BCL11A-12126	+	CAAACACCCACCUCUGGC	18	14315
  BCL11A-12127	+	ACAAACACCCACCUCUGGC	19	14316
  BCL11A-10118	+	GACAAACACCCACCUCUGGC	20	14317
  BCL11A-12128	+	GGACAAACACCCACCUCUGGC	21	14318
  BCL11A-12129	+	GGGACAAACACCCACCUCUGGC	22	14319
  BCL11A-12130	+	CGGGACAAACACCCACCUCUGGC	23	14320
  BCL11A-12131	+	GCGGGACAAACACCCACCUCUGGC	24	14321
  BCL11A-12132	+	GCGCUCGGGAAACUUUGC	18	14322
  BCL11A-12133	+	UGCGCUCGGGAAACUUUGC	19	14323
  BCL11A-12134	+	CUGCGCUCGGGAAACUUUGC	20	14324
  BCL11A-12135	+	GCUGCGCUCGGGAAACUUUGC	21	14325
  BCL11A-12136	+	GGCUGCGCUCGGGAAACUUUGC	22	14326
  BCL11A-12137	+	CGGCUGCGCUCGGGAAACUUUGC	23	14327
  BCL11A-12138	+	GCGGCUGCGCUCGGGAAACUUUGC	24	14328
  BCL11A-12139	+	UCCCGACUCCGCGGACUC	18	14329
  BCL11A-12140	+	CUCCCGACUCCGCGGACUC	19	14330
  BCL11A-10122	+	UCUCCCGACUCCGCGGACUC	20	14331
  BCL11A-12141	+	CUCUCCCGACUCCGCGGACUC	21	14332
  BCL11A-12142	+	CCUCUCCCGACUCCGCGGACUC	22	14333
  BCL11A-12143	+	CCCUCUCCCGACUCCGCGGACUC	23	14334
  BCL11A-12144	+	CCCCUCUCCCGACUCCGCGGACUC	24	14335
  BCL11A-12145	+	GAGCCCGCGGCUGCGCUC	18	14336
  BCL11A-12146	+	CGAGCCCGCGGCUGCGCUC	19	14337
  BCL11A-10126	+	CCGAGCCCGCGGCUGCGCUC	20	14338
  BCL11A-12147	+	CCCGAGCCCGCGGCUGCGCUC	21	14339
  BCL11A-12148	+	CCCCGAGCCCGCGGCUGCGCUC	22	14340
  BCL11A-12149	+	GCCCCGAGCCCGCGGCUGCGCUC	23	14341
  BCL11A-12150	+	AGCCCCGAGCCCGCGGCUGCGCUC	24	14342
  BCL11A-12151	+	AGCCAGGUAGAGUUGCUC	18	14343
  BCL11A-12152	+	AAGCCAGGUAGAGUUGCUC	19	14344
  BCL11A-12153	+	GAAGCCAGGUAGAGUUGCUC	20	14345
  BCL11A-12154	+	GGAAGCCAGGUAGAGUUGCUC	21	14346
  BCL11A-12155	+	GGGAAGCCAGGUAGAGUUGCUC	22	14347
  BCL11A-12156	+	AGGGAAGCCAGGUAGAGUUGCUC	23	14348
  BCL11A-12157	+	GAGGGAAGCCAGGUAGAGUUGCUC	24	14349
  BCL11A-12158	+	GGGCAGCGCCCAAGUCUC	18	14350
  BCL11A-12159	+	AGGGCAGCGCCCAAGUCUC	19	14351
  BCL11A-12160	+	AAGGGCAGCGCCCAAGUCUC	20	14352
  BCL11A-12161	+	GAAGGGCAGCGCCCAAGUCUC	21	14353
  BCL11A-12162	+	GGAAGGGCAGCGCCCAAGUCUC	22	14354
  BCL11A-12163	+	CGGAAGGGCAGCGCCCAAGUCUC	23	14355
  BCL11A-12164	+	CCGGAAGGGCAGCGCCCAAGUCUC	24	14356
  BCL11A-12165	+	UUUGGAGGGCUGCGGGUC	18	14357
  BCL11A-12166	+	GUUUGGAGGGCUGCGGGUC	19	14358
  BCL11A-10129	+	AGUUUGGAGGGCUGCGGGUC	20	14359
  BCL11A-12167	+	AAGUUUGGAGGGCUGCGGGUC	21	14360
  BCL11A-12168	+	UAAGUUUGGAGGGCUGCGGGUC	22	14361
  BCL11A-12169	+	CUAAGUUUGGAGGGCUGCGGGUC	23	14362
  BCL11A-12170	+	CCUAAGUUUGGAGGGCUGCGGGUC	24	14363
  BCL11A-12171	+	CGGCGGAAAGGAGGAAAG	18	14364
  BCL11A-12172	+	GCGGCGGAAAGGAGGAAAG	19	14365
  BCL11A-10136	+	AGCGGCGGAAAGGAGGAAAG	20	14366
  BCL11A-12173	+	AAGCGGCGGAAAGGAGGAAAG	21	14367
  BCL11A-12174	+	AAAGCGGCGGAAAGGAGGAAAG	22	14368
  BCL11A-12175	+	UAAAGCGGCGGAAAGGAGGAAAG	23	14369
  BCL11A-12176	+	AUAAAGCGGCGGAAAGGAGGAAAG	24	14370
  BCL11A-12177	+	AAAUAAAGCGGCGGAAAG	18	14371
  BCL11A-12178	+	GAAAUAAAGCGGCGGAAAG	19	14372
  BCL11A-12179	+	AGAAAUAAAGCGGCGGAAAG	20	14373
  BCL11A-12180	+	GAGAAAUAAAGCGGCGGAAAG	21	14374
  BCL11A-12181	+	AGAGAAAUAAAGCGGCGGAAAG	22	14375
  BCL11A-12182	+	AAGAGAAAUAAAGCGGCGGAAAG	23	14376
  BCL11A-12183	+	AAAGAGAAAUAAAGCGGCGGAAAG	24	14377
  BCL11A-12184	+	CCCGCGCGGCCUGGAAAG	18	14378
  BCL11A-12185	+	GCCCGCGCGGCCUGGAAAG	19	14379
  BCL11A-10137	+	AGCCCGCGCGGCCUGGAAAG	20	14380
  BCL11A-12186	+	GAGCCCGCGCGGCCUGGAAAG	21	14381
  BCL11A-12187	+	GGAGCCCGCGCGGCCUGGAAAG	22	14382
  BCL11A-12188	+	AGGAGCCCGCGCGGCCUGGAAAG	23	14383
  BCL11A-12189	+	CAGGAGCCCGCGCGGCCUGGAAAG	24	14384
  BCL11A-12190	+	AAGAAAAAUCACCCGAAG	18	14385
  BCL11A-12191	+	AAAGAAAAAUCACCCGAAG	19	14386
  BCL11A-12192	+	CAAAGAAAAAUCACCCGAAG	20	14387
  BCL11A-12193	+	GCAAAGAAAAAUCACCCGAAG	21	14388
  BCL11A-12194	+	AGCAAAGAAAAAUCACCCGAAG	22	14389
  BCL11A-12195	+	CAGCAAAGAAAAAUCACCCGAAG	23	14390
  BCL11A-12196	+	ACAGCAAAGAAAAAUCACCCGAAG	24	14391
  BCL11A-12197	+	AGCCGGCACAAAAGGCAG	18	14392
  BCL11A-12198	+	GAGCCGGCACAAAAGGCAG	19	14393
  BCL11A-10144	+	GGAGCCGGCACAAAAGGCAG	20	14394
  BCL11A-12199	+	AGGAGCCGGCACAAAAGGCAG	21	14395
  BCL11A-12200	+	GAGGAGCCGGCACAAAAGGCAG	22	14396
  BCL11A-12201	+	CGAGGAGCCGGCACAAAAGGCAG	23	14397
  BCL11A-12202	+	GCGAGGAGCCGGCACAAAAGGCAG	24	14398
  BCL11A-12203	+	GCGGAAAGGAGGAAAGAG	18	14399
  BCL11A-12204	+	GGCGGAAAGGAGGAAAGAG	19	14400
  BCL11A-12205	+	CGGCGGAAAGGAGGAAAGAG	20	14401
  BCL11A-12206	+	GCGGCGGAAAGGAGGAAAGAG	21	14402
  BCL11A-12207	+	AGCGGCGGAAAGGAGGAAAGAG	22	14403
  BCL11A-12208	+	AAGCGGCGGAAAGGAGGAAAGAG	23	14404
  BCL11A-12209	+	AAAGCGGCGGAAAGGAGGAAAGAG	24	14405
  BCL11A-12210	+	AUCACCCGAAGUUGAGAG	18	14406
  BCL11A-12211	+	AAUCACCCGAAGUUGAGAG	19	14407
  BCL11A-12212	+	AAAUCACCCGAAGUUGAGAG	20	14408
  BCL11A-12213	+	AAAAUCACCCGAAGUUGAGAG	21	14409
  BCL11A-12214	+	AAAAAUCACCCGAAGUUGAGAG	22	14410
  BCL11A-12215	+	GAAAAAUCACCCGAAGUUGAGAG	23	14411
  BCL11A-12216	+	AGAAAAAUCACCCGAAGUUGAGAG	24	14412
  BCL11A-12217	+	CGGGAAACUUUGCCCGAG	18	14413
  BCL11A-12218	+	UCGGGAAACUUUGCCCGAG	19	14414
  BCL11A-12219	+	CUCGGGAAACUUUGCCCGAG	20	14415
  BCL11A-12220	+	GCUCGGGAAACUUUGCCCGAG	21	14416
  BCL11A-12221	+	CGCUCGGGAAACUUUGCCCGAG	22	14417
  BCL11A-12222	+	GCGCUCGGGAAACUUUGCCCGAG	23	14418
  BCL11A-12223	+	UGCGCUCGGGAAACUUUGCCCGAG	24	14419
  BCL11A-12224	+	AGCUCCGCAGCGGGCGAG	18	14420
  BCL11A-12225	+	CAGCUCCGCAGCGGGCGAG	19	14421
  BCL11A-10148	+	ACAGCUCCGCAGCGGGCGAG	20	14422
  BCL11A-12226	+	UACAGCUCCGCAGCGGGCGAG	21	14423
  BCL11A-12227	+	UUACAGCUCCGCAGCGGGCGAG	22	14424
  BCL11A-12228	+	GUUACAGCUCCGCAGCGGGCGAG	23	14425
  BCL11A-12229	+	AGUUACAGCUCCGCAGCGGGCGAG	24	14426
  BCL11A-12230	+	CGCAGCGGGCGAGGGGAG	18	14427
  BCL11A-12231	+	CCGCAGCGGGCGAGGGGAG	19	14428
  BCL11A-12232	+	UCCGCAGCGGGCGAGGGGAG	20	14429
  BCL11A-12233	+	CUCCGCAGCGGGCGAGGGGAG	21	14430
  BCL11A-12234	+	GCUCCGCAGCGGGCGAGGGGAG	22	14431
  BCL11A-12235	+	AGCUCCGCAGCGGGCGAGGGGAG	23	14432
  BCL11A-12236	+	CAGCUCCGCAGCGGGCGAGGGGAG	24	14433
  BCL11A-12237	+	CCAUUUUCUUACGGUGAG	18	14434
  BCL11A-12238	+	CCCAUUUUCUUACGGUGAG	19	14435
  BCL11A-10154	+	CCCCAUUUUCUUACGGUGAG	20	14436
  BCL11A-12239	+	CCCCCAUUUUCUUACGGUGAG	21	14437
  BCL11A-12240	+	CCCCCCAUUUUCUUACGGUGAG	22	14438
  BCL11A-12241	+	CCCCCCCAUUUUCUUACGGUGAG	23	14439
  BCL11A-12242	+	ACCCCCCCAUUUUCUUACGGUGAG	24	14440
  BCL11A-12243	+	CCUGGAAAGAGGGGACCG	18	14441
  BCL11A-12244	+	GCCUGGAAAGAGGGGACCG	19	14442
  BCL11A-10159	+	GGCCUGGAAAGAGGGGACCG	20	14443
  BCL11A-12245	+	CGGCCUGGAAAGAGGGGACCG	21	14444
  BCL11A-12246	+	GCGGCCUGGAAAGAGGGGACCG	22	14445
  BCL11A-12247	+	CGCGGCCUGGAAAGAGGGGACCG	23	14446
  BCL11A-12248	+	GCGCGGCCUGGAAAGAGGGGACCG	24	14447
  BCL11A-12249	+	CUCGGGAAACUUUGCCCG	18	14448
  BCL11A-12250	+	GCUCGGGAAACUUUGCCCG	19	14449
  BCL11A-10163	+	CGCUCGGGAAACUUUGCCCG	20	14450
  BCL11A-12251	+	GCGCUCGGGAAACUUUGCCCG	21	14451
  BCL11A-12252	+	UGCGCUCGGGAAACUUUGCCCG	22	14452
  BCL11A-12253	+	CUGCGCUCGGGAAACUUUGCCCG	23	14453
  BCL11A-12254	+	GCUGCGCUCGGGAAACUUUGCCCG	24	14454
  BCL11A-12255	+	GAAAAGAGAAAUAAAGCG	18	14455
  BCL11A-12256	+	CGAAAAGAGAAAUAAAGCG	19	14456
  BCL11A-12257	+	UCGAAAAGAGAAAUAAAGCG	20	14457
  BCL11A-12258	+	UUCGAAAAGAGAAAUAAAGCG	21	14458
  BCL11A-12259	+	UUUCGAAAAGAGAAAUAAAGCG	22	14459
  BCL11A-12260	+	UUUUCGAAAAGAGAAAUAAAGCG	23	14460
  BCL11A-12261	+	CUUUUCGAAAAGAGAAAUAAAGCG	24	14461
  BCL11A-12262	+	UCCGCGGACUCAGGAGCG	18	14462
  BCL11A-12263	+	CUCCGCGGACUCAGGAGCG	19	14463
  BCL11A-12264	+	ACUCCGCGGACUCAGGAGCG	20	14464
  BCL11A-12265	+	GACUCCGCGGACUCAGGAGCG	21	14465
  BCL11A-12266	+	CGACUCCGCGGACUCAGGAGCG	22	14466
  BCL11A-12267	+	CCGACUCCGCGGACUCAGGAGCG	23	14467
  BCL11A-12268	+	CCCGACUCCGCGGACUCAGGAGCG	24	14468
  BCL11A-12269	+	CGCGGGAGGGCAAGCGCG	18	14469
  BCL11A-12270	+	GCGCGGGAGGGCAAGCGCG	19	14470
  BCL11A-10178	+	GGCGCGGGAGGGCAAGCGCG	20	14471
  BCL11A-12271	+	ACAGCUCCGCAGCGGGCG	18	14472
  BCL11A-12272	+	UACAGCUCCGCAGCGGGCG	19	14473
  BCL11A-10180	+	UUACAGCUCCGCAGCGGGCG	20	14474
  BCL11A-12273	+	GUUACAGCUCCGCAGCGGGCG	21	14475
  BCL11A-12274	+	AGUUACAGCUCCGCAGCGGGCG	22	14476
  BCL11A-12275	+	AAGUUACAGCUCCGCAGCGGGCG	23	14477
  BCL11A-12276	+	CAAGUUACAGCUCCGCAGCGGGCG	24	14478
  BCL11A-12277	+	GCUGGGGAAGCGCGGGCG	18	14479
  BCL11A-12278	+	GGCUGGGGAAGCGCGGGCG	19	14480
  BCL11A-12279	+	GGGCUGGGGAAGCGCGGGCG	20	14481
  BCL11A-12280	+	CGGGCUGGGGAAGCGCGGGCG	21	14482
  BCL11A-12281	+	CCGGGCUGGGGAAGCGCGGGCG	22	14483
  BCL11A-12282	+	CCCGGGCUGGGGAAGCGCGGGCG	23	14484
  BCL11A-12283	+	CCCCGGGCUGGGGAAGCGCGGGCG	24	14485
  BCL11A-12284	+	UGCAAAACUGGCGGGGCG	18	14486
  BCL11A-12285	+	UUGCAAAACUGGCGGGGCG	19	14487
  BCL11A-10181	+	UUUGCAAAACUGGCGGGGCG	20	14488
  BCL11A-12286	+	UUUUGCAAAACUGGCGGGGCG	21	14489
  BCL11A-12287	+	AUUUUGCAAAACUGGCGGGGCG	22	14490
  BCL11A-12288	+	UAUUUUGCAAAACUGGCGGGGCG	23	14491
  BCL11A-12289	+	UUAUUUUGCAAAACUGGCGGGGCG	24	14492
  BCL11A-12290	+	AAUAAAGCGGCGGAAAGG	18	14493
  BCL11A-12291	+	AAAUAAAGCGGCGGAAAGG	19	14494
  BCL11A-10185	+	GAAAUAAAGCGGCGGAAAGG	20	14495
  BCL11A-12292	+	AGAAAUAAAGCGGCGGAAAGG	21	14496
  BCL11A-12293	+	GAGAAAUAAAGCGGCGGAAAGG	22	14497
  BCL11A-12294	+	AGAGAAAUAAAGCGGCGGAAAGG	23	14498
  BCL11A-12295	+	AAGAGAAAUAAAGCGGCGGAAAGG	24	14499
  BCL11A-12296	+	CCGAGGGCGCCCCCAAGG	18	14500
  BCL11A-12297	+	CCCGAGGGCGCCCCCAAGG	19	14501
  BCL11A-12298	+	GCCCGAGGGCGCCCCCAAGG	20	14502
  BCL11A-12299	+	GGCCCGAGGGCGCCCCCAAGG	21	14503
  BCL11A-12300	+	GGGCCCGAGGGCGCCCCCAAGG	22	14504
  BCL11A-12301	+	GGGGCCCGAGGGCGCCCCCAAGG	23	14505
  BCL11A-12302	+	CGGGGCCCGAGGGCGCCCCCAAGG	24	14506
  BCL11A-12303	+	AGAGGCAGGCGGCGCAGG	18	14507
  BCL11A-12304	+	GAGAGGCAGGCGGCGCAGG	19	14508
  BCL11A-12305	+	GGAGAGGCAGGCGGCGCAGG	20	14509
  BCL11A-12306	+	GGGAGAGGCAGGCGGCGCAGG	21	14510
  BCL11A-12307	+	GGGGAGAGGCAGGCGGCGCAGG	22	14511
  BCL11A-12308	+	CGGGGAGAGGCAGGCGGCGCAGG	23	14512
  BCL11A-12309	+	CCGGGGAGAGGCAGGCGGCGCAGG	24	14513
  BCL11A-12310	+	GCAGCGGGCGAGGGGAGG	18	14514
  BCL11A-12311	+	CGCAGCGGGCGAGGGGAGG	19	14515
  BCL11A-10190	+	CCGCAGCGGGCGAGGGGAGG	20	14516
  BCL11A-12312	+	UCCGCAGCGGGCGAGGGGAGG	21	14517
  BCL11A-12313	+	CUCCGCAGCGGGCGAGGGGAGG	22	14518
  BCL11A-12314	+	GCUCCGCAGCGGGCGAGGGGAGG	23	14519
  BCL11A-12315	+	AGCUCCGCAGCGGGCGAGGGGAGG	24	14520
  BCL11A-12316	+	GGAGGGCUGCGGGUCCGG	18	14521
  BCL11A-12317	+	UGGAGGGCUGCGGGUCCGG	19	14522
  BCL11A-12318	+	UUGGAGGGCUGCGGGUCCGG	20	14523
  BCL11A-12319	+	UUUGGAGGGCUGCGGGUCCGG	21	14524
  BCL11A-12320	+	GUUUGGAGGGCUGCGGGUCCGG	22	14525
  BCL11A-12321	+	AGUUUGGAGGGCUGCGGGUCCGG	23	14526
  BCL11A-12322	+	AAGUUUGGAGGGCUGCGGGUCCGG	24	14527
  BCL11A-12323	+	AAAAGAGAAAUAAAGCGG	18	14528
  BCL11A-12324	+	GAAAAGAGAAAUAAAGCGG	19	14529
  BCL11A-10193	+	CGAAAAGAGAAAUAAAGCGG	20	14530
  BCL11A-12325	+	UCGAAAAGAGAAAUAAAGCGG	21	14531
  BCL11A-12326	+	UUCGAAAAGAGAAAUAAAGCGG	22	14532
  BCL11A-12327	+	UUUCGAAAAGAGAAAUAAAGCGG	23	14533
  BCL11A-12328	+	UUUUCGAAAAGAGAAAUAAAGCGG	24	14534
  BCL11A-12329	+	GUUACAGCUCCGCAGCGG	18	14535
  BCL11A-12330	+	AGUUACAGCUCCGCAGCGG	19	14536
  BCL11A-12331	+	AAGUUACAGCUCCGCAGCGG	20	14537
  BCL11A-12332	+	CAAGUUACAGCUCCGCAGCGG	21	14538
  BCL11A-12333	+	CCAAGUUACAGCUCCGCAGCGG	22	14539
  BCL11A-12334	+	UCCAAGUUACAGCUCCGCAGCGG	23	14540
  BCL11A-12335	+	CUCCAAGUUACAGCUCCGCAGCGG	24	14541
  BCL11A-12336	+	CGGGCUGGGGAAGCGCGG	18	14542
  BCL11A-12337	+	CCGGGCUGGGGAAGCGCGG	19	14543
  BCL11A-12338	+	CCCGGGCUGGGGAAGCGCGG	20	14544
  BCL11A-12339	+	CCCCGGGCUGGGGAAGCGCGG	21	14545
  BCL11A-12340	+	GCCCCGGGCUGGGGAAGCGCGG	22	14546
  BCL11A-12341	+	AGCCCCGGGCUGGGGAAGCGCGG	23	14547
  BCL11A-12342	+	CAGCCCCGGGCUGGGGAAGCGCGG	24	14548
  BCL11A-12343	+	CUGGGGAAGCGCGGGCGG	18	14549
  BCL11A-12344	+	GCUGGGGAAGCGCGGGCGG	19	14550
  BCL11A-10197	+	GGCUGGGGAAGCGCGGGCGG	20	14551
  BCL11A-12345	+	GGGCUGGGGAAGCGCGGGCGG	21	14552
  BCL11A-12346	+	CGGGCUGGGGAAGCGCGGGCGG	22	14553
  BCL11A-12347	+	CCGGGCUGGGGAAGCGCGGGCGG	23	14554
  BCL11A-12348	+	CCCGGGCUGGGGAAGCGCGGGCGG	24	14555
  BCL11A-12349	+	GCAAAACUGGCGGGGCGG	18	14556
  BCL11A-12350	+	UGCAAAACUGGCGGGGCGG	19	14557
  BCL11A-10198	+	UUGCAAAACUGGCGGGGCGG	20	14558
  BCL11A-12351	+	UUUGCAAAACUGGCGGGGCGG	21	14559
  BCL11A-12352	+	UUUUGCAAAACUGGCGGGGCGG	22	14560
  BCL11A-12353	+	AUUUUGCAAAACUGGCGGGGCGG	23	14561
  BCL11A-12354	+	UAUUUUGCAAAACUGGCGGGGCGG	24	14562
  BCL11A-12355	+	UGGAAAGAGGGGACCGGG	18	14563
  BCL11A-12356	+	CUGGAAAGAGGGGACCGGG	19	14564
  BCL11A-12357	+	CCUGGAAAGAGGGGACCGGG	20	14565
  BCL11A-12358	+	GCCUGGAAAGAGGGGACCGGG	21	14566
  BCL11A-12359	+	GGCCUGGAAAGAGGGGACCGGG	22	14567
  BCL11A-12360	+	CGGCCUGGAAAGAGGGGACCGGG	23	14568
  BCL11A-12361	+	GCGGCCUGGAAAGAGGGGACCGGG	24	14569
  BCL11A-12362	+	GGAGGCUGCAGCCCCGGG	18	14570
  BCL11A-12363	+	GGGAGGCUGCAGCCCCGGG	19	14571
  BCL11A-12364	+	CGGGAGGCUGCAGCCCCGGG	20	14572
  BCL11A-12365	+	CCGGGAGGCUGCAGCCCCGGG	21	14573
  BCL11A-12366	+	ACCGGGAGGCUGCAGCCCCGGG	22	14574
  BCL11A-12367	+	CACCGGGAGGCUGCAGCCCCGGG	23	14575
  BCL11A-12368	+	GCACCGGGAGGCUGCAGCCCCGGG	24	14576
  BCL11A-12369	+	GGGCUGGGGAAGCGCGGG	18	14577
  BCL11A-12370	+	CGGGCUGGGGAAGCGCGGG	19	14578
  BCL11A-10203	+	CCGGGCUGGGGAAGCGCGGG	20	14579
  BCL11A-12371	+	CCCGGGCUGGGGAAGCGCGGG	21	14580
  BCL11A-12372	+	CCCCGGGCUGGGGAAGCGCGGG	22	14581
  BCL11A-12373	+	GCCCCGGGCUGGGGAAGCGCGGG	23	14582
  BCL11A-12374	+	AGCCCCGGGCUGGGGAAGCGCGGG	24	14583
  BCL11A-12375	+	CAAAACUGGCGGGGCGGG	18	14584
  BCL11A-12376	+	GCAAAACUGGCGGGGCGGG	19	14585
  BCL11A-10204	+	UGCAAAACUGGCGGGGCGGG	20	14586
  BCL11A-12377	+	UUGCAAAACUGGCGGGGCGGG	21	14587
  BCL11A-12378	+	UUUGCAAAACUGGCGGGGCGGG	22	14588
  BCL11A-12379	+	UUUUGCAAAACUGGCGGGGCGGG	23	14589
  BCL11A-12380	+	AUUUUGCAAAACUGGCGGGGCGGG	24	14590
  BCL11A-12381	+	UUUUGCAAAACUGGCGGG	18	14591
  BCL11A-12382	+	AUUUUGCAAAACUGGCGGG	19	14592
  BCL11A-12383	+	UAUUUUGCAAAACUGGCGGG	20	14593
  BCL11A-12384	+	UUAUUUUGCAAAACUGGCGGG	21	14594
  BCL11A-12385	+	AUUAUUUUGCAAAACUGGCGGG	22	14595
  BCL11A-12386	+	CAUUAUUUUGCAAAACUGGCGGG	23	14596
  BCL11A-12387	+	UCAUUAUUUUGCAAAACUGGCGGG	24	14597
  BCL11A-12388	+	GCGUGUGGACGCCAGGGG	18	14598
  BCL11A-12389	+	CGCGUGUGGACGCCAGGGG	19	14599
  BCL11A-12390	+	CCGCGUGUGGACGCCAGGGG	20	14600
  BCL11A-12391	+	CCCGCGUGUGGACGCCAGGGG	21	14601
  BCL11A-12392	+	CCCCGCGUGUGGACGCCAGGGG	22	14602
  BCL11A-12393	+	UCCCCGCGUGUGGACGCCAGGGG	23	14603
  BCL11A-12394	+	CUCCCCGCGUGUGGACGCCAGGGG	24	14604
  BCL11A-12395	+	AAAACUGGCGGGGCGGGG	18	14605
  BCL11A-12396	+	CAAAACUGGCGGGGCGGGG	19	14606
  BCL11A-10207	+	GCAAAACUGGCGGGGCGGGG	20	14607
  BCL11A-12397	+	UGCAAAACUGGCGGGGCGGGG	21	14608
  BCL11A-12398	+	UUGCAAAACUGGCGGGGCGGGG	22	14609
  BCL11A-12399	+	UUUGCAAAACUGGCGGGGCGGGG	23	14610
  BCL11A-12400	+	UUUUGCAAAACUGGCGGGGCGGGG	24	14611
  BCL11A-12401	+	UUUGCAAAACUGGCGGGG	18	14612
  BCL11A-12402	+	UUUUGCAAAACUGGCGGGG	19	14613
  BCL11A-10208	+	AUUUUGCAAAACUGGCGGGG	20	14614
  BCL11A-12403	+	UAUUUUGCAAAACUGGCGGGG	21	14615
  BCL11A-12404	+	UUAUUUUGCAAAACUGGCGGGG	22	14616
  BCL11A-12405	+	AUUAUUUUGCAAAACUGGCGGGG	23	14617
  BCL11A-12406	+	CAUUAUUUUGCAAAACUGGCGGGG	24	14618
  BCL11A-12407	+	CGGGCGAGGGGAGGUGGG	18	14619
  BCL11A-12408	+	GCGGGCGAGGGGAGGUGGG	19	14620
  BCL11A-10213	+	AGCGGGCGAGGGGAGGUGGG	20	14621
  BCL11A-12409	+	CAGCGGGCGAGGGGAGGUGGG	21	14622
  BCL11A-12410	+	GCAGCGGGCGAGGGGAGGUGGG	22	14623
  BCL11A-12411	+	CGCAGCGGGCGAGGGGAGGUGGG	23	14624
  BCL11A-12412	+	CCGCAGCGGGCGAGGGGAGGUGGG	24	14625
  BCL11A-12413	+	AUUAUUUUGCAAAACUGG	18	14626
  BCL11A-12414	+	CAUUAUUUUGCAAAACUGG	19	14627
  BCL11A-10215	+	UCAUUAUUUUGCAAAACUGG	20	14628
  BCL11A-12415	+	UUCAUUAUUUUGCAAAACUGG	21	14629
  BCL11A-12416	+	GUUCAUUAUUUUGCAAAACUGG	22	14630
  BCL11A-12417	+	UGUUCAUUAUUUUGCAAAACUGG	23	14631
  BCL11A-12418	+	UUGUUCAUUAUUUUGCAAAACUGG	24	14632
  BCL11A-12419	+	ACAAACACCCACCUCUGG	18	14633
  BCL11A-12420	+	GACAAACACCCACCUCUGG	19	14634
  BCL11A-12421	+	GGACAAACACCCACCUCUGG	20	14635
  BCL11A-12422	+	GGGACAAACACCCACCUCUGG	21	14636
  BCL11A-12423	+	CGGGACAAACACCCACCUCUGG	22	14637
  BCL11A-12424	+	GCGGGACAAACACCCACCUCUGG	23	14638
  BCL11A-12425	+	AGCGGGACAAACACCCACCUCUGG	24	14639
  BCL11A-12426	+	GCGGGCGAGGGGAGGUGG	18	14640
  BCL11A-12427	+	AGCGGGCGAGGGGAGGUGG	19	14641
  BCL11A-12428	+	CAGCGGGCGAGGGGAGGUGG	20	14642
  BCL11A-12429	+	GCAGCGGGCGAGGGGAGGUGG	21	14643
  BCL11A-12430	+	CGCAGCGGGCGAGGGGAGGUGG	22	14644
  BCL11A-12431	+	CCGCAGCGGGCGAGGGGAGGUGG	23	14645
  BCL11A-12432	+	UCCGCAGCGGGCGAGGGGAGGUGG	24	14646
  BCL11A-12433	+	CAUUAUUUUGCAAAACUG	18	14647
  BCL11A-12434	+	UCAUUAUUUUGCAAAACUG	19	14648
  BCL11A-12435	+	UUCAUUAUUUUGCAAAACUG	20	14649
  BCL11A-12436	+	GUUCAUUAUUUUGCAAAACUG	21	14650
  BCL11A-12437	+	UGUUCAUUAUUUUGCAAAACUG	22	14651
  BCL11A-12438	+	UUGUUCAUUAUUUUGCAAAACUG	23	14652
  BCL11A-12439	+	AUUGUUCAUUAUUUUGCAAAACUG	24	14653
  BCL11A-12440	+	GGCUGCAGCCCCGGGCUG	18	14654
  BCL11A-12441	+	AGGCUGCAGCCCCGGGCUG	19	14655
  BCL11A-10226	+	GAGGCUGCAGCCCCGGGCUG	20	14656
  BCL11A-12442	+	GGAGGCUGCAGCCCCGGGCUG	21	14657
  BCL11A-12443	+	GGGAGGCUGCAGCCCCGGGCUG	22	14658
  BCL11A-12444	+	CGGGAGGCUGCAGCCCCGGGCUG	23	14659
  BCL11A-12445	+	CCGGGAGGCUGCAGCCCCGGGCUG	24	14660
  BCL11A-12446	+	GCCACUUUCUCACUAUUG	18	14661
  BCL11A-12447	+	UGCCACUUUCUCACUAUUG	19	14662
  BCL11A-10230	+	GUGCCACUUUCUCACUAUUG	20	14663
  BCL11A-12448	+	AGUGCCACUUUCUCACUAUUG	21	14664
  BCL11A-12449	+	CAGUGCCACUUUCUCACUAUUG	22	14665
  BCL11A-12450	+	ACAGUGCCACUUUCUCACUAUUG	23	14666
  BCL11A-12451	+	CACAGUGCCACUUUCUCACUAUUG	24	14667
  BCL11A-12452	+	GAAUCCAGCCUAAGUUUG	18	14668
  BCL11A-12453	+	GGAAUCCAGCCUAAGUUUG	19	14669
  BCL11A-12454	+	CGGAAUCCAGCCUAAGUUUG	20	14670
  BCL11A-12455	+	GCGGAAUCCAGCCUAAGUUUG	21	14671
  BCL11A-12456	+	CGCGGAAUCCAGCCUAAGUUUG	22	14672
  BCL11A-12457	+	ACGCGGAAUCCAGCCUAAGUUUG	23	14673
  BCL11A-12458	+	AACGCGGAAUCCAGCCUAAGUUUG	24	14674
  BCL11A-12459	+	CUCCCGACUCCGCGGACU	18	14675
  BCL11A-12460	+	UCUCCCGACUCCGCGGACU	19	14676
  BCL11A-12461	+	CUCUCCCGACUCCGCGGACU	20	14677
  BCL11A-12462	+	CCUCUCCCGACUCCGCGGACU	21	14678
  BCL11A-12463	+	CCCUCUCCCGACUCCGCGGACU	22	14679
  BCL11A-12464	+	CCCCUCUCCCGACUCCGCGGACU	23	14680
  BCL11A-12465	+	GCCCCUCUCCCGACUCCGCGGACU	24	14681
  BCL11A-12466	+	CGAGCCCGCGGCUGCGCU	18	14682
  BCL11A-12467	+	CCGAGCCCGCGGCUGCGCU	19	14683
  BCL11A-10239	+	CCCGAGCCCGCGGCUGCGCU	20	14684
  BCL11A-12468	+	CCCCGAGCCCGCGGCUGCGCU	21	14685
  BCL11A-12469	+	GCCCCGAGCCCGCGGCUGCGCU	22	14686
  BCL11A-12470	+	AGCCCCGAGCCCGCGGCUGCGCU	23	14687
  BCL11A-12471	+	AAGCCCCGAGCCCGCGGCUGCGCU	24	14688
  BCL11A-12472	+	AGGCUGCAGCCCCGGGCU	18	14689
  BCL11A-12473	+	GAGGCUGCAGCCCCGGGCU	19	14690
  BCL11A-10240	+	GGAGGCUGCAGCCCCGGGCU	20	14691
  BCL11A-12474	+	GGGAGGCUGCAGCCCCGGGCU	21	14692
  BCL11A-12475	+	CGGGAGGCUGCAGCCCCGGGCU	22	14693
  BCL11A-12476	+	CCGGGAGGCUGCAGCCCCGGGCU	23	14694
  BCL11A-12477	+	ACCGGGAGGCUGCAGCCCCGGGCU	24	14695
  BCL11A-12478	+	GCGGAAUCCAGCCUAAGU	18	14696
  BCL11A-12479	+	CGCGGAAUCCAGCCUAAGU	19	14697
  BCL11A-12480	+	ACGCGGAAUCCAGCCUAAGU	20	14698
  BCL11A-12481	+	AACGCGGAAUCCAGCCUAAGU	21	14699
  BCL11A-12482	+	CAACGCGGAAUCCAGCCUAAGU	22	14700
  BCL11A-12483	+	GCAACGCGGAAUCCAGCCUAAGU	23	14701
  BCL11A-12484	+	GGCAACGCGGAAUCCAGCCUAAGU	24	14702
  BCL11A-12485	+	CAUUUUCUUACGGUGAGU	18	14703
  BCL11A-12486	+	CCAUUUUCUUACGGUGAGU	19	14704
  BCL11A-10244	+	CCCAUUUUCUUACGGUGAGU	20	14705
  BCL11A-12487	+	CCCCAUUUUCUUACGGUGAGU	21	14706
  BCL11A-12488	+	CCCCCAUUUUCUUACGGUGAGU	22	14707
  BCL11A-12489	+	CCCCCCAUUUUCUUACGGUGAGU	23	14708
  BCL11A-12490	+	CCCCCCCAUUUUCUUACGGUGAGU	24	14709
  BCL11A-12491	+	CGCGCUCGCUCCCCGCGU	18	14710
  BCL11A-12492	+	CCGCGCUCGCUCCCCGCGU	19	14711
  BCL11A-12493	+	GCCGCGCUCGCUCCCCGCGU	20	14712
  BCL11A-12494	+	CGCCGCGCUCGCUCCCCGCGU	21	14713
  BCL11A-12495	+	CCGCCGCGCUCGCUCCCCGCGU	22	14714
  BCL11A-12496	+	GCCGCCGCGCUCGCUCCCCGCGU	23	14715
  BCL11A-12497	+	CGCCGCCGCGCUCGCUCCCCGCGU	24	14716
  BCL11A-12498	+	CAGCGGGCGAGGGGAGGU	18	14717
  BCL11A-12499	+	GCAGCGGGCGAGGGGAGGU	19	14718
  BCL11A-10247	+	CGCAGCGGGCGAGGGGAGGU	20	14719
  BCL11A-12500	+	CCGCAGCGGGCGAGGGGAGGU	21	14720
  BCL11A-12501	+	UCCGCAGCGGGCGAGGGGAGGU	22	14721
  BCL11A-12502	+	CUCCGCAGCGGGCGAGGGGAGGU	23	14722
  BCL11A-12503	+	GCUCCGCAGCGGGCGAGGGGAGGU	24	14723
  BCL11A-12504	+	GUUUGGAGGGCUGCGGGU	18	14724
  BCL11A-12505	+	AGUUUGGAGGGCUGCGGGU	19	14725
  BCL11A-12506	+	AAGUUUGGAGGGCUGCGGGU	20	14726
  BCL11A-12507	+	UAAGUUUGGAGGGCUGCGGGU	21	14727
  BCL11A-12508	+	CUAAGUUUGGAGGGCUGCGGGU	22	14728
  BCL11A-12509	+	CCUAAGUUUGGAGGGCUGCGGGU	23	14729
  BCL11A-12510	+	GCCUAAGUUUGGAGGGCUGCGGGU	24	14730
  BCL11A-12511	+	UGCCACUUUCUCACUAUU	18	14731
  BCL11A-12512	+	GUGCCACUUUCUCACUAUU	19	14732
  BCL11A-12513	+	AGUGCCACUUUCUCACUAUU	20	14733
  BCL11A-12514	+	CAGUGCCACUUUCUCACUAUU	21	14734
  BCL11A-12515	+	ACAGUGCCACUUUCUCACUAUU	22	14735
  BCL11A-12516	+	CACAGUGCCACUUUCUCACUAUU	23	14736
  BCL11A-12517	+	CCACAGUGCCACUUUCUCACUAUU	24	14737
  BCL11A-12518	+	GAAAAAUCACCCGAAGUU	18	14738
  BCL11A-12519	+	AGAAAAAUCACCCGAAGUU	19	14739
  BCL11A-12520	+	AAGAAAAAUCACCCGAAGUU	20	14740
  BCL11A-12521	+	AAAGAAAAAUCACCCGAAGUU	21	14741
  BCL11A-12522	+	CAAAGAAAAAUCACCCGAAGUU	22	14742
  BCL11A-12523	+	GCAAAGAAAAAUCACCCGAAGUU	23	14743
  BCL11A-12524	+	AGCAAAGAAAAAUCACCCGAAGUU	24	14744
  BCL11A-12525	+	CGGAAUCCAGCCUAAGUU	18	14745
  BCL11A-12526	+	GCGGAAUCCAGCCUAAGUU	19	14746
  BCL11A-10257	+	CGCGGAAUCCAGCCUAAGUU	20	14747
  BCL11A-12527	+	ACGCGGAAUCCAGCCUAAGUU	21	14748
  BCL11A-12528	+	AACGCGGAAUCCAGCCUAAGUU	22	14749
  BCL11A-12529	+	CAACGCGGAAUCCAGCCUAAGUU	23	14750
  BCL11A-12530	+	GCAACGCGGAAUCCAGCCUAAGUU	24	14751
  BCL11A-12531	+	GAAUCAUUGCAUUCCUUU	18	14752
  BCL11A-12532	+	GGAAUCAUUGCAUUCCUUU	19	14753
  BCL11A-12533	+	UGGAAUCAUUGCAUUCCUUU	20	14754
  BCL11A-12534	+	GUGGAAUCAUUGCAUUCCUUU	21	14755
  BCL11A-12535	+	AGUGGAAUCAUUGCAUUCCUUU	22	14756
  BCL11A-12536	+	GAGUGGAAUCAUUGCAUUCCUUU	23	14757
  BCL11A-12537	+	GGAGUGGAAUCAUUGCAUUCCUUU	24	14758
  BCL11A-12538	-	CCACUCACCGUAAGAAAA	18	14759
  BCL11A-12539	-	CCCACUCACCGUAAGAAAA	19	14760
  BCL11A-10024	-	UCCCACUCACCGUAAGAAAA	20	14761
  BCL11A-12540	-	UUCCCACUCACCGUAAGAAAA	21	14762
  BCL11A-12541	-	CUUCCCACUCACCGUAAGAAAA	22	14763
  BCL11A-12542	-	GCUUCCCACUCACCGUAAGAAAA	23	14764
  BCL11A-12543	-	UGCUUCCCACUCACCGUAAGAAAA	24	14765
  BCL11A-12544	-	CCCACUCACCGUAAGAAA	18	14766
  BCL11A-12545	-	UCCCACUCACCGUAAGAAA	19	14767
  BCL11A-12546	-	UUCCCACUCACCGUAAGAAA	20	14768
  BCL11A-12547	-	CUUCCCACUCACCGUAAGAAA	21	14769
  BCL11A-12548	-	GCUUCCCACUCACCGUAAGAAA	22	14770
  BCL11A-12549	-	UGCUUCCCACUCACCGUAAGAAA	23	14771
  BCL11A-12550	-	UUGCUUCCCACUCACCGUAAGAAA	24	14772
  BCL11A-12551	-	UGGGAGCUGGUGGGGAAA	18	14773
  BCL11A-12552	-	GUGGGAGCUGGUGGGGAAA	19	14774
  BCL11A-10028	-	GGUGGGAGCUGGUGGGGAAA	20	14775
  BCL11A-12553	-	GGGUGGGAGCUGGUGGGGAAA	21	14776
  BCL11A-12554	-	GGGGUGGGAGCUGGUGGGGAAA	22	14777
  BCL11A-12555	-	GGGGGUGGGAGCUGGUGGGGAAA	23	14778
  BCL11A-12556	-	UGGGGGUGGGAGCUGGUGGGGAAA	24	14779
  BCL11A-12557	-	AACGAUUCCCGGGGAGAA	18	14780
  BCL11A-12558	-	AAACGAUUCCCGGGGAGAA	19	14781
  BCL11A-12559	-	AAAACGAUUCCCGGGGAGAA	20	14782
  BCL11A-12560	-	AAAAACGAUUCCCGGGGAGAA	21	14783
  BCL11A-12561	-	AAAAAACGAUUCCCGGGGAGAA	22	14784
  BCL11A-12562	-	UAAAAAACGAUUCCCGGGGAGAA	23	14785
  BCL11A-12563	-	CUAAAAAACGAUUCCCGGGGAGAA	24	14786
  BCL11A-12564	-	UUUAUUUCUCUUUUCGAA	18	14787
  BCL11A-12565	-	CUUUAUUUCUCUUUUCGAA	19	14788
  BCL11A-12566	-	GCUUUAUUUCUCUUUUCGAA	20	14789
  BCL11A-12567	-	CGCUUUAUUUCUCUUUUCGAA	21	14790
  BCL11A-12568	-	CCGCUUUAUUUCUCUUUUCGAA	22	14791
  BCL11A-12569	-	GCCGCUUUAUUUCUCUUUUCGAA	23	14792
  BCL11A-12570	-	CGCCGCUUUAUUUCUCUUUUCGAA	24	14793
  BCL11A-12571	-	GUGGGAGCUGGUGGGGAA	18	14794
  BCL11A-12572	-	GGUGGGAGCUGGUGGGGAA	19	14795
  BCL11A-10032	-	GGGUGGGAGCUGGUGGGGAA	20	14796
  BCL11A-12573	-	GGGGUGGGAGCUGGUGGGGAA	21	14797
  BCL11A-12574	-	GGGGGUGGGAGCUGGUGGGGAA	22	14798
  BCL11A-12575	-	UGGGGGUGGGAGCUGGUGGGGAA	23	14799
  BCL11A-12576	-	CUGGGGGUGGGAGCUGGUGGGGAA	24	14800
  BCL11A-12577	-	GAAAGUGGCACUGUGGAA	18	14801
  BCL11A-12578	-	AGAAAGUGGCACUGUGGAA	19	14802
  BCL11A-10033	-	GAGAAAGUGGCACUGUGGAA	20	14803
  BCL11A-12579	-	UGAGAAAGUGGCACUGUGGAA	21	14804
  BCL11A-12580	-	GUGAGAAAGUGGCACUGUGGAA	22	14805
  BCL11A-12581	-	AGUGAGAAAGUGGCACUGUGGAA	23	14806
  BCL11A-12582	-	UAGUGAGAAAGUGGCACUGUGGAA	24	14807
  BCL11A-12583	-	CUCACGGUCAAGUGUGCA	18	14808
  BCL11A-12584	-	GCUCACGGUCAAGUGUGCA	19	14809
  BCL11A-12585	-	CGCUCACGGUCAAGUGUGCA	20	14810
  BCL11A-12586	-	GCGCUCACGGUCAAGUGUGCA	21	14811
  BCL11A-12587	-	CGCGCUCACGGUCAAGUGUGCA	22	14812
  BCL11A-12588	-	GCGCGCUCACGGUCAAGUGUGCA	23	14813
  BCL11A-12589	-	AGCGCGCUCACGGUCAAGUGUGCA	24	14814
  BCL11A-12590	-	GGAGAGGGGCCGCGGCGA	18	14815
  BCL11A-12591	-	GGGAGAGGGGCCGCGGCGA	19	14816
  BCL11A-10043	-	CGGGAGAGGGGCCGCGGCGA	20	14817
  BCL11A-12592	-	UCGGGAGAGGGGCCGCGGCGA	21	14818
  BCL11A-12593	-	GUCGGGAGAGGGGCCGCGGCGA	22	14819
  BCL11A-12594	-	AGUCGGGAGAGGGGCCGCGGCGA	23	14820
  BCL11A-12595	-	GAGUCGGGAGAGGGGCCGCGGCGA	24	14821
  BCL11A-12596	-	CCGUGGGACCGGGAAGGA	18	14822
  BCL11A-12597	-	GCCGUGGGACCGGGAAGGA	19	14823
  BCL11A-10045	-	AGCCGUGGGACCGGGAAGGA	20	14824
  BCL11A-12598	-	GAGCCGUGGGACCGGGAAGGA	21	14825
  BCL11A-12599	-	AGAGCCGUGGGACCGGGAAGGA	22	14826
  BCL11A-12600	-	GAGAGCCGUGGGACCGGGAAGGA	23	14827
  BCL11A-12601	-	GGAGAGCCGUGGGACCGGGAAGGA	24	14828
  BCL11A-12602	-	GAGUCCGCGGAGUCGGGA	18	14829
  BCL11A-12603	-	UGAGUCCGCGGAGUCGGGA	19	14830
  BCL11A-12604	-	CUGAGUCCGCGGAGUCGGGA	20	14831
  BCL11A-12605	-	CCUGAGUCCGCGGAGUCGGGA	21	14832
  BCL11A-12606	-	UCCUGAGUCCGCGGAGUCGGGA	22	14833
  BCL11A-12607	-	CUCCUGAGUCCGCGGAGUCGGGA	23	14834
  BCL11A-12608	-	GCUCCUGAGUCCGCGGAGUCGGGA	24	14835
  BCL11A-12609	-	GGCGUCCACACGCGGGGA	18	14836
  BCL11A-12610	-	UGGCGUCCACACGCGGGGA	19	14837
  BCL11A-12611	-	CUGGCGUCCACACGCGGGGA	20	14838
  BCL11A-12612	-	CCUGGCGUCCACACGCGGGGA	21	14839
  BCL11A-12613	-	CCCUGGCGUCCACACGCGGGGA	22	14840
  BCL11A-12614	-	CCCCUGGCGUCCACACGCGGGGA	23	14841
  BCL11A-12615	-	GCCCCUGGCGUCCACACGCGGGGA	24	14842
  BCL11A-12616	-	GCGCGGCGGCGGCGGGGA	18	14843
  BCL11A-12617	-	AGCGCGGCGGCGGCGGGGA	19	14844
  BCL11A-10051	-	GAGCGCGGCGGCGGCGGGGA	20	14845
  BCL11A-12618	-	CGAGCGCGGCGGCGGCGGGGA	21	14846
  BCL11A-12619	-	GCGAGCGCGGCGGCGGCGGGGA	22	14847
  BCL11A-12620	-	AGCGAGCGCGGCGGCGGCGGGGA	23	14848
  BCL11A-12621	-	GAGCGAGCGCGGCGGCGGCGGGGA	24	14849
  BCL11A-12622	-	GGUGGGAGCUGGUGGGGA	18	14850
  BCL11A-12623	-	GGGUGGGAGCUGGUGGGGA	19	14851
  BCL11A-12624	-	GGGGUGGGAGCUGGUGGGGA	20	14852
  BCL11A-12625	-	GGGGGUGGGAGCUGGUGGGGA	21	14853
  BCL11A-12626	-	UGGGGGUGGGAGCUGGUGGGGA	22	14854
  BCL11A-12627	-	CUGGGGGUGGGAGCUGGUGGGGA	23	14855
  BCL11A-12628	-	CCUGGGGGUGGGAGCUGGUGGGGA	24	14856
  BCL11A-12629	-	ACGGGGAGAGCCGUGGGA	18	14857
  BCL11A-12630	-	GACGGGGAGAGCCGUGGGA	19	14858
  BCL11A-12631	-	CGACGGGGAGAGCCGUGGGA	20	14859
  BCL11A-12632	-	GCGACGGGGAGAGCCGUGGGA	21	14860
  BCL11A-12633	-	GGCGACGGGGAGAGCCGUGGGA	22	14861
  BCL11A-12634	-	CGGCGACGGGGAGAGCCGUGGGA	23	14862
  BCL11A-12635	-	GCGGCGACGGGGAGAGCCGUGGGA	24	14863
  BCL11A-12636	-	AGAAAGUGGCACUGUGGA	18	14864
  BCL11A-12637	-	GAGAAAGUGGCACUGUGGA	19	14865
  BCL11A-12638	-	UGAGAAAGUGGCACUGUGGA	20	14866
  BCL11A-12639	-	GUGAGAAAGUGGCACUGUGGA	21	14867
  BCL11A-12640	-	AGUGAGAAAGUGGCACUGUGGA	22	14868
  BCL11A-12641	-	UAGUGAGAAAGUGGCACUGUGGA	23	14869
  BCL11A-12642	-	AUAGUGAGAAAGUGGCACUGUGGA	24	14870
  BCL11A-12643	-	CGCCAGUUUUGCAAAAUA	18	14871
  BCL11A-12644	-	CCGCCAGUUUUGCAAAAUA	19	14872
  BCL11A-12645	-	CCCGCCAGUUUUGCAAAAUA	20	14873
  BCL11A-12646	-	CCCCGCCAGUUUUGCAAAAUA	21	14874
  BCL11A-12647	-	GCCCCGCCAGUUUUGCAAAAUA	22	14875
  BCL11A-12648	-	CGCCCCGCCAGUUUUGCAAAAUA	23	14876
  BCL11A-12649	-	CCGCCCCGCCAGUUUUGCAAAAUA	24	14877
  BCL11A-12650	-	GUAGUCAUCCCCACAAUA	18	14878
  BCL11A-12651	-	AGUAGUCAUCCCCACAAUA	19	14879
  BCL11A-12652	-	AAGUAGUCAUCCCCACAAUA	20	14880
  BCL11A-12653	-	AAAGUAGUCAUCCCCACAAUA	21	14881
  BCL11A-12654	-	GAAAGUAGUCAUCCCCACAAUA	22	14882
  BCL11A-12655	-	GGAAAGUAGUCAUCCCCACAAUA	23	14883
  BCL11A-12656	-	AGGAAAGUAGUCAUCCCCACAAUA	24	14884
  BCL11A-12657	-	GGGAAGUGGGUGUGCGUA	18	14885
  BCL11A-12658	-	GGGGAAGUGGGUGUGCGUA	19	14886
  BCL11A-10055	-	AGGGGAAGUGGGUGUGCGUA	20	14887
  BCL11A-12659	-	GAGGGGAAGUGGGUGUGCGUA	21	14888
  BCL11A-12660	-	GGAGGGGAAGUGGGUGUGCGUA	22	14889
  BCL11A-12661	-	GGGAGGGGAAGUGGGUGUGCGUA	23	14890
  BCL11A-12662	-	GGGGAGGGGAAGUGGGUGUGCGUA	24	14891
  BCL11A-12663	-	UAAGAAAAUGGGGGGGUA	18	14892
  BCL11A-12664	-	GUAAGAAAAUGGGGGGGUA	19	14893
  BCL11A-10056	-	CGUAAGAAAAUGGGGGGGUA	20	14894
  BCL11A-12665	-	CCGUAAGAAAAUGGGGGGGUA	21	14895
  BCL11A-12666	-	ACCGUAAGAAAAUGGGGGGGUA	22	14896
  BCL11A-12667	-	CACCGUAAGAAAAUGGGGGGGUA	23	14897
  BCL11A-12668	-	UCACCGUAAGAAAAUGGGGGGGUA	24	14898
  BCL11A-12669	-	AACAACUCACAUGCAAAC	18	14899
  BCL11A-12670	-	GAACAACUCACAUGCAAAC	19	14900
  BCL11A-12671	-	CGAACAACUCACAUGCAAAC	20	14901
  BCL11A-12672	-	GCGAACAACUCACAUGCAAAC	21	14902
  BCL11A-12673	-	UGCGAACAACUCACAUGCAAAC	22	14903
  BCL11A-12674	-	UUGCGAACAACUCACAUGCAAAC	23	14904
  BCL11A-12675	-	GUUGCGAACAACUCACAUGCAAAC	24	14905
  BCL11A-12676	-	CCGCUGCGGAGCUGUAAC	18	14906
  BCL11A-12677	-	CCCGCUGCGGAGCUGUAAC	19	14907
  BCL11A-12678	-	GCCCGCUGCGGAGCUGUAAC	20	14908
  BCL11A-12679	-	CGCCCGCUGCGGAGCUGUAAC	21	14909
  BCL11A-12680	-	UCGCCCGCUGCGGAGCUGUAAC	22	14910
  BCL11A-12681	-	CUCGCCCGCUGCGGAGCUGUAAC	23	14911
  BCL11A-12682	-	CCUCGCCCGCUGCGGAGCUGUAAC	24	14912
  BCL11A-12683	-	GGCCCCUGGCGUCCACAC	18	14913
  BCL11A-12684	-	CGGCCCCUGGCGUCCACAC	19	14914
  BCL11A-12685	-	UCGGCCCCUGGCGUCCACAC	20	14915
  BCL11A-12686	-	UUCGGCCCCUGGCGUCCACAC	21	14916
  BCL11A-12687	-	CUUCGGCCCCUGGCGUCCACAC	22	14917
  BCL11A-12688	-	ACUUCGGCCCCUGGCGUCCACAC	23	14918
  BCL11A-12689	-	UACUUCGGCCCCUGGCGUCCACAC	24	14919
  BCL11A-12690	-	GCGCGGGCUCCUGGAGAC	18	14920
  BCL11A-12691	-	CGCGCGGGCUCCUGGAGAC	19	14921
  BCL11A-12692	-	CCGCGCGGGCUCCUGGAGAC	20	14922
  BCL11A-12693	-	GCCGCGCGGGCUCCUGGAGAC	21	14923
  BCL11A-12694	-	GGCCGCGCGGGCUCCUGGAGAC	22	14924
  BCL11A-12695	-	AGGCCGCGCGGGCUCCUGGAGAC	23	14925
  BCL11A-12696	-	CAGGCCGCGCGGGCUCCUGGAGAC	24	14926
  BCL11A-12697	-	GAGAGGGGCCGCGGCGAC	18	14927
  BCL11A-12698	-	GGAGAGGGGCCGCGGCGAC	19	14928
  BCL11A-10061	-	GGGAGAGGGGCCGCGGCGAC	20	14929
  BCL11A-12699	-	CGGGAGAGGGGCCGCGGCGAC	21	14930
  BCL11A-12700	-	UCGGGAGAGGGGCCGCGGCGAC	22	14931
  BCL11A-12701	-	GUCGGGAGAGGGGCCGCGGCGAC	23	14932
  BCL11A-12702	-	AGUCGGGAGAGGGGCCGCGGCGAC	24	14933
  BCL11A-12703	-	CGUGGGACCGGGAAGGAC	18	14934
  BCL11A-12704	-	CCGUGGGACCGGGAAGGAC	19	14935
  BCL11A-10062	-	GCCGUGGGACCGGGAAGGAC	20	14936
  BCL11A-12705	-	AGCCGUGGGACCGGGAAGGAC	21	14937
  BCL11A-12706	-	GAGCCGUGGGACCGGGAAGGAC	22	14938
  BCL11A-12707	-	AGAGCCGUGGGACCGGGAAGGAC	23	14939
  BCL11A-12708	-	GAGAGCCGUGGGACCGGGAAGGAC	24	14940
  BCL11A-12709	-	CGGGGAGAGCCGUGGGAC	18	14941
  BCL11A-12710	-	ACGGGGAGAGCCGUGGGAC	19	14942
  BCL11A-10065	-	GACGGGGAGAGCCGUGGGAC	20	14943
  BCL11A-12711	-	CGACGGGGAGAGCCGUGGGAC	21	14944
  BCL11A-12712	-	GCGACGGGGAGAGCCGUGGGAC	22	14945
  BCL11A-12713	-	GGCGACGGGGAGAGCCGUGGGAC	23	14946
  BCL11A-12714	-	CGGCGACGGGGAGAGCCGUGGGAC	24	14947
  BCL11A-12715	-	ACAACUCACAUGCAAACC	18	14948
  BCL11A-12716	-	AACAACUCACAUGCAAACC	19	14949
  BCL11A-10066	-	GAACAACUCACAUGCAAACC	20	14950
  BCL11A-12717	-	CGAACAACUCACAUGCAAACC	21	14951
  BCL11A-12718	-	GCGAACAACUCACAUGCAAACC	22	14952
  BCL11A-12719	-	UGCGAACAACUCACAUGCAAACC	23	14953
  BCL11A-12720	-	UUGCGAACAACUCACAUGCAAACC	24	14954
  BCL11A-12721	-	GGGGAGAGCCGUGGGACC	18	14955
  BCL11A-12722	-	CGGGGAGAGCCGUGGGACC	19	14956
  BCL11A-10070	-	ACGGGGAGAGCCGUGGGACC	20	14957
  BCL11A-12723	-	GACGGGGAGAGCCGUGGGACC	21	14958
  BCL11A-12724	-	CGACGGGGAGAGCCGUGGGACC	22	14959
  BCL11A-12725	-	GCGACGGGGAGAGCCGUGGGACC	23	14960
  BCL11A-12726	-	GGCGACGGGGAGAGCCGUGGGACC	24	14961
  BCL11A-12727	-	UCGGCCUUGGGGGCGCCC	18	14962
  BCL11A-12728	-	CUCGGCCUUGGGGGCGCCC	19	14963
  BCL11A-12729	-	GCUCGGCCUUGGGGGCGCCC	20	14964
  BCL11A-12730	-	GGCUCGGCCUUGGGGGCGCCC	21	14965
  BCL11A-12731	-	UGGCUCGGCCUUGGGGGCGCCC	22	14966
  BCL11A-12732	-	CUGGCUCGGCCUUGGGGGCGCCC	23	14967
  BCL11A-12733	-	CCUGGCUCGGCCUUGGGGGCGCCC	24	14968
  BCL11A-12734	-	GUCUAAAAAACGAUUCCC	18	14969
  BCL11A-12735	-	AGUCUAAAAAACGAUUCCC	19	14970
  BCL11A-10082	-	AAGUCUAAAAAACGAUUCCC	20	14971
  BCL11A-12736	-	CAAGUCUAAAAAACGAUUCCC	21	14972
  BCL11A-12737	-	ACAAGUCUAAAAAACGAUUCCC	22	14973
  BCL11A-12738	-	UACAAGUCUAAAAAACGAUUCCC	23	14974
  BCL11A-12739	-	GUACAAGUCUAAAAAACGAUUCCC	24	14975
  BCL11A-12740	-	GCCCGCGCUUCCCCAGCC	18	14976
  BCL11A-12741	-	CGCCCGCGCUUCCCCAGCC	19	14977
  BCL11A-10084	-	CCGCCCGCGCUUCCCCAGCC	20	14978
  BCL11A-12742	-	UCCGCCCGCGCUUCCCCAGCC	21	14979
  BCL11A-12743	-	CUCCGCCCGCGCUUCCCCAGCC	22	14980
  BCL11A-12744	-	CCUCCGCCCGCGCUUCCCCAGCC	23	14981
  BCL11A-12745	-	CCCUCCGCCCGCGCUUCCCCAGCC	24	14982
  BCL11A-12746	-	AGUUUCCCGAGCGCAGCC	18	14983
  BCL11A-12747	-	AAGUUUCCCGAGCGCAGCC	19	14984
  BCL11A-12748	-	AAAGUUUCCCGAGCGCAGCC	20	14985
  BCL11A-12749	-	CAAAGUUUCCCGAGCGCAGCC	21	14986
  BCL11A-12750	-	GCAAAGUUUCCCGAGCGCAGCC	22	14987
  BCL11A-12751	-	GGCAAAGUUUCCCGAGCGCAGCC	23	14988
  BCL11A-12752	-	GGGCAAAGUUUCCCGAGCGCAGCC	24	14989
  BCL11A-12753	-	GCGGCGACGGGGAGAGCC	18	14990
  BCL11A-12754	-	CGCGGCGACGGGGAGAGCC	19	14991
  BCL11A-12755	-	CCGCGGCGACGGGGAGAGCC	20	14992
  BCL11A-12756	-	GCCGCGGCGACGGGGAGAGCC	21	14993
  BCL11A-12757	-	GGCCGCGGCGACGGGGAGAGCC	22	14994
  BCL11A-12758	-	GGGCCGCGGCGACGGGGAGAGCC	23	14995
  BCL11A-12759	-	GGGGCCGCGGCGACGGGGAGAGCC	24	14996
  BCL11A-12760	-	CCGGUCCCUGGCUCGGCC	18	14997
  BCL11A-12761	-	CCCGGUCCCUGGCUCGGCC	19	14998
  BCL11A-12762	-	UCCCGGUCCCUGGCUCGGCC	20	14999
  BCL11A-12763	-	CCAGGCCGCGCGGGCUCC	18	15000
  BCL11A-12764	-	UCCAGGCCGCGCGGGCUCC	19	15001
  BCL11A-10091	-	UUCCAGGCCGCGCGGGCUCC	20	15002
  BCL11A-12765	-	UUUCCAGGCCGCGCGGGCUCC	21	15003
  BCL11A-12766	-	CUUUCCAGGCCGCGCGGGCUCC	22	15004
  BCL11A-12767	-	UCUUUCCAGGCCGCGCGGGCUCC	23	15005
  BCL11A-12768	-	CUCUUUCCAGGCCGCGCGGGCUCC	24	15006
  BCL11A-12769	-	UUCUUUGCUGUCCUCUCC	18	15007
  BCL11A-12770	-	UUUCUUUGCUGUCCUCUCC	19	15008
  BCL11A-12771	-	UUUUCUUUGCUGUCCUCUCC	20	15009
  BCL11A-12772	-	UUUUUCUUUGCUGUCCUCUCC	21	15010
  BCL11A-12773	-	AUUUUUCUUUGCUGUCCUCUCC	22	15011
  BCL11A-12774	-	GAUUUUUCUUUGCUGUCCUCUCC	23	15012
  BCL11A-12775	-	UGAUUUUUCUUUGCUGUCCUCUCC	24	15013
  BCL11A-12776	-	CCCGGCGCUCCUGAGUCC	18	15014
  BCL11A-12777	-	CCCCGGCGCUCCUGAGUCC	19	15015
  BCL11A-12778	-	CCCCCGGCGCUCCUGAGUCC	20	15016
  BCL11A-12779	-	GCCCCCGGCGCUCCUGAGUCC	21	15017
  BCL11A-12780	-	GGCCCCCGGCGCUCCUGAGUCC	22	15018
  BCL11A-12781	-	GGGCCCCCGGCGCUCCUGAGUCC	23	15019
  BCL11A-12782	-	GGGGCCCCCGGCGCUCCUGAGUCC	24	15020
  BCL11A-12783	-	GUACGGAGGAGGGUGUCC	18	15021
  BCL11A-12784	-	CGUACGGAGGAGGGUGUCC	19	15022
  BCL11A-10094	-	GCGUACGGAGGAGGGUGUCC	20	15023
  BCL11A-12785	-	UGCGUACGGAGGAGGGUGUCC	21	15024
  BCL11A-12786	-	GUGCGUACGGAGGAGGGUGUCC	22	15025
  BCL11A-12787	-	UGUGCGUACGGAGGAGGGUGUCC	23	15026
  BCL11A-12788	-	GUGUGCGUACGGAGGAGGGUGUCC	24	15027
  BCL11A-12789	-	AGUCUAAAAAACGAUUCC	18	15028
  BCL11A-12790	-	AAGUCUAAAAAACGAUUCC	19	15029
  BCL11A-10095	-	CAAGUCUAAAAAACGAUUCC	20	15030
  BCL11A-12791	-	ACAAGUCUAAAAAACGAUUCC	21	15031
  BCL11A-12792	-	UACAAGUCUAAAAAACGAUUCC	22	15032
  BCL11A-12793	-	GUACAAGUCUAAAAAACGAUUCC	23	15033
  BCL11A-12794	-	AGUACAAGUCUAAAAAACGAUUCC	24	15034
  BCL11A-12795	-	CGCCCGCGCUUCCCCAGC	18	15035
  BCL11A-12796	-	CCGCCCGCGCUUCCCCAGC	19	15036
  BCL11A-12797	-	UCCGCCCGCGCUUCCCCAGC	20	15037
  BCL11A-12798	-	CUCCGCCCGCGCUUCCCCAGC	21	15038
  BCL11A-12799	-	CCUCCGCCCGCGCUUCCCCAGC	22	15039
  BCL11A-12800	-	CCCUCCGCCCGCGCUUCCCCAGC	23	15040
  BCL11A-12801	-	UCCCUCCGCCCGCGCUUCCCCAGC	24	15041
  BCL11A-12802	-	CACGGUCAAGUGUGCAGC	18	15042
  BCL11A-12803	-	UCACGGUCAAGUGUGCAGC	19	15043
  BCL11A-10100	-	CUCACGGUCAAGUGUGCAGC	20	15044
  BCL11A-12804	-	GCUCACGGUCAAGUGUGCAGC	21	15045
  BCL11A-12805	-	CGCUCACGGUCAAGUGUGCAGC	22	15046
  BCL11A-12806	-	GCGCUCACGGUCAAGUGUGCAGC	23	15047
  BCL11A-12807	-	CGCGCUCACGGUCAAGUGUGCAGC	24	15048
  BCL11A-12808	-	CCCCUGGCGUCCACACGC	18	15049
  BCL11A-12809	-	GCCCCUGGCGUCCACACGC	19	15050
  BCL11A-10103	-	GGCCCCUGGCGUCCACACGC	20	15051
  BCL11A-12810	-	CGGCCCCUGGCGUCCACACGC	21	15052
  BCL11A-12811	-	UCGGCCCCUGGCGUCCACACGC	22	15053
  BCL11A-12812	-	UUCGGCCCCUGGCGUCCACACGC	23	15054
  BCL11A-12813	-	CUUCGGCCCCUGGCGUCCACACGC	24	15055
  BCL11A-12814	-	CCCCUCUUUCCAGGCCGC	18	15056
  BCL11A-12815	-	UCCCCUCUUUCCAGGCCGC	19	15057
  BCL11A-12816	-	GUCCCCUCUUUCCAGGCCGC	20	15058
  BCL11A-12817	-	GGUCCCCUCUUUCCAGGCCGC	21	15059
  BCL11A-12818	-	CGGUCCCCUCUUUCCAGGCCGC	22	15060
  BCL11A-12819	-	CCGGUCCCCUCUUUCCAGGCCGC	23	15061
  BCL11A-12820	-	CCCGGUCCCCUCUUUCCAGGCCGC	24	15062
  BCL11A-12821	-	GCCGCCUUUUGUUCCGGC	18	15063
  BCL11A-12822	-	UGCCGCCUUUUGUUCCGGC	19	15064
  BCL11A-12823	-	CUGCCGCCUUUUGUUCCGGC	20	15065
  BCL11A-12824	-	ACUGCCGCCUUUUGUUCCGGC	21	15066
  BCL11A-12825	-	CACUGCCGCCUUUUGUUCCGGC	22	15067
  BCL11A-12826	-	GCACUGCCGCCUUUUGUUCCGGC	23	15068
  BCL11A-12827	-	GGCACUGCCGCCUUUUGUUCCGGC	24	15069
  BCL11A-12828	-	AGCGAGCGCGGCGGCGGC	18	15070
  BCL11A-12829	-	GAGCGAGCGCGGCGGCGGC	19	15071
  BCL11A-10114	-	GGAGCGAGCGCGGCGGCGGC	20	15072
  BCL11A-12830	-	GGGAGCGAGCGCGGCGGCGGC	21	15073
  BCL11A-12831	-	GGGGAGCGAGCGCGGCGGCGGC	22	15074
  BCL11A-12832	-	CGGGGAGCGAGCGCGGCGGCGGC	23	15075
  BCL11A-12833	-	GCGGGGAGCGAGCGCGGCGGCGGC	24	15076
  BCL11A-12834	-	CCGAGCGCAGCCGCGGGC	18	15077
  BCL11A-12835	-	CCCGAGCGCAGCCGCGGGC	19	15078
  BCL11A-12836	-	UCCCGAGCGCAGCCGCGGGC	20	15079
  BCL11A-12837	-	UUCCCGAGCGCAGCCGCGGGC	21	15080
  BCL11A-12838	-	UUUCCCGAGCGCAGCCGCGGGC	22	15081
  BCL11A-12839	-	GUUUCCCGAGCGCAGCCGCGGGC	23	15082
  BCL11A-12840	-	AGUUUCCCGAGCGCAGCCGCGGGC	24	15083
  BCL11A-12841	-	UCCAGGCCGCGCGGGCUC	18	15084
  BCL11A-12842	-	UUCCAGGCCGCGCGGGCUC	19	15085
  BCL11A-12843	-	UUUCCAGGCCGCGCGGGCUC	20	15086
  BCL11A-12844	-	CUUUCCAGGCCGCGCGGGCUC	21	15087
  BCL11A-12845	-	UCUUUCCAGGCCGCGCGGGCUC	22	15088
  BCL11A-12846	-	CUCUUUCCAGGCCGCGCGGGCUC	23	15089
  BCL11A-12847	-	CCUCUUUCCAGGCCGCGCGGGCUC	24	15090
  BCL11A-12848	-	UCCUGAGUCCGCGGAGUC	18	15091
  BCL11A-12849	-	CUCCUGAGUCCGCGGAGUC	19	15092
  BCL11A-10128	-	GCUCCUGAGUCCGCGGAGUC	20	15093
  BCL11A-12850	-	CGCUCCUGAGUCCGCGGAGUC	21	15094
  BCL11A-12851	-	GCGCUCCUGAGUCCGCGGAGUC	22	15095
  BCL11A-12852	-	GGCGCUCCUGAGUCCGCGGAGUC	23	15096
  BCL11A-12853	-	CGGCGCUCCUGAGUCCGCGGAGUC	24	15097
  BCL11A-12854	-	CGUACGGAGGAGGGUGUC	18	15098
  BCL11A-12855	-	GCGUACGGAGGAGGGUGUC	19	15099
  BCL11A-10130	-	UGCGUACGGAGGAGGGUGUC	20	15100
  BCL11A-12856	-	GUGCGUACGGAGGAGGGUGUC	21	15101
  BCL11A-12857	-	UGUGCGUACGGAGGAGGGUGUC	22	15102
  BCL11A-12858	-	GUGUGCGUACGGAGGAGGGUGUC	23	15103
  BCL11A-12859	-	GGUGUGCGUACGGAGGAGGGUGUC	24	15104
  BCL11A-12860	-	AAGUCUAAAAAACGAUUC	18	15105
  BCL11A-12861	-	CAAGUCUAAAAAACGAUUC	19	15106
  BCL11A-12862	-	ACAAGUCUAAAAAACGAUUC	20	15107
  BCL11A-12863	-	UACAAGUCUAAAAAACGAUUC	21	15108
  BCL11A-12864	-	GUACAAGUCUAAAAAACGAUUC	22	15109
  BCL11A-12865	-	AGUACAAGUCUAAAAAACGAUUC	23	15110
  BCL11A-12866	-	GAGUACAAGUCUAAAAAACGAUUC	24	15111
  BCL11A-12867	-	CUCCUCGGGCAAAGUUUC	18	15112
  BCL11A-12868	-	UCUCCUCGGGCAAAGUUUC	19	15113
  BCL11A-12869	-	CUCUCCUCGGGCAAAGUUUC	20	15114
  BCL11A-12870	-	CCUCUCCUCGGGCAAAGUUUC	21	15115
  BCL11A-12871	-	UCCUCUCCUCGGGCAAAGUUUC	22	15116
  BCL11A-12872	-	GUCCUCUCCUCGGGCAAAGUUUC	23	15117
  BCL11A-12873	-	UGUCCUCUCCUCGGGCAAAGUUUC	24	15118
  BCL11A-12874	-	UCACGGUCAAGUGUGCAG	18	15119
  BCL11A-12875	-	CUCACGGUCAAGUGUGCAG	19	15120
  BCL11A-10145	-	GCUCACGGUCAAGUGUGCAG	20	15121
  BCL11A-12876	-	CGCUCACGGUCAAGUGUGCAG	21	15122
  BCL11A-12877	-	GCGCUCACGGUCAAGUGUGCAG	22	15123
  BCL11A-12878	-	CGCGCUCACGGUCAAGUGUGCAG	23	15124
  BCL11A-12879	-	GCGCGCUCACGGUCAAGUGUGCAG	24	15125
  BCL11A-12880	-	UUCCCGGGGAGAAAAGAG	18	15126
  BCL11A-12881	-	AUUCCCGGGGAGAAAAGAG	19	15127
  BCL11A-12882	-	GAUUCCCGGGGAGAAAAGAG	20	15128
  BCL11A-12883	-	CGAUUCCCGGGGAGAAAAGAG	21	15129
  BCL11A-12884	-	ACGAUUCCCGGGGAGAAAAGAG	22	15130
  BCL11A-12885	-	AACGAUUCCCGGGGAGAAAAGAG	23	15131
  BCL11A-12886	-	AAACGAUUCCCGGGGAGAAAAGAG	24	15132
  BCL11A-12887	-	GCUCCUGAGUCCGCGGAG	18	15133
  BCL11A-12888	-	CGCUCCUGAGUCCGCGGAG	19	15134
  BCL11A-12889	-	GCGCUCCUGAGUCCGCGGAG	20	15135
  BCL11A-12890	-	GGCGCUCCUGAGUCCGCGGAG	21	15136
  BCL11A-12891	-	CGGCGCUCCUGAGUCCGCGGAG	22	15137
  BCL11A-12892	-	CCGGCGCUCCUGAGUCCGCGGAG	23	15138
  BCL11A-12893	-	CCCGGCGCUCCUGAGUCCGCGGAG	24	15139
  BCL11A-12894	-	AGUCCGCGGAGUCGGGAG	18	15140
  BCL11A-12895	-	GAGUCCGCGGAGUCGGGAG	19	15141
  BCL11A-10150	-	UGAGUCCGCGGAGUCGGGAG	20	15142
  BCL11A-12896	-	CUGAGUCCGCGGAGUCGGGAG	21	15143
  BCL11A-12897	-	CCUGAGUCCGCGGAGUCGGGAG	22	15144
  BCL11A-12898	-	UCCUGAGUCCGCGGAGUCGGGAG	23	15145
  BCL11A-12899	-	CUCCUGAGUCCGCGGAGUCGGGAG	24	15146
  BCL11A-12900	-	CGCGGCGGCGGCGGGGAG	18	15147
  BCL11A-12901	-	GCGCGGCGGCGGCGGGGAG	19	15148
  BCL11A-10152	-	AGCGCGGCGGCGGCGGGGAG	20	15149
  BCL11A-12902	-	GAGCGCGGCGGCGGCGGGGAG	21	15150
  BCL11A-12903	-	CGAGCGCGGCGGCGGCGGGGAG	22	15151
  BCL11A-12904	-	GCGAGCGCGGCGGCGGCGGGGAG	23	15152
  BCL11A-12905	-	AGCGAGCGCGGCGGCGGCGGGGAG	24	15153
  BCL11A-11434	-	CGCGUGUGUGGGGGGGAG	18	15154
  BCL11A-11435	-	CCGCGUGUGUGGGGGGGAG	19	15155
  BCL11A-11436	-	UCCGCGUGUGUGGGGGGGAG	20	15156
  BCL11A-11437	-	GUCCGCGUGUGUGGGGGGGAG	21	15157
  BCL11A-11438	-	AGUCCGCGUGUGUGGGGGGGAG	22	15158
  BCL11A-11439	-	GAGUCCGCGUGUGUGGGGGGGAG	23	15159
  BCL11A-11440	-	AGAGUCCGCGUGUGUGGGGGGGAG	24	15160
  BCL11A-12906	-	GCCCCUGGCGUCCACACG	18	15161
  BCL11A-12907	-	GGCCCCUGGCGUCCACACG	19	15162
  BCL11A-10156	-	CGGCCCCUGGCGUCCACACG	20	15163
  BCL11A-12908	-	UCGGCCCCUGGCGUCCACACG	21	15164
  BCL11A-12909	-	UUCGGCCCCUGGCGUCCACACG	22	15165
  BCL11A-12910	-	CUUCGGCCCCUGGCGUCCACACG	23	15166
  BCL11A-12911	-	ACUUCGGCCCCUGGCGUCCACACG	24	15167
  BCL11A-12912	-	AGAGGGGCCGCGGCGACG	18	15168
  BCL11A-12913	-	GAGAGGGGCCGCGGCGACG	19	15169
  BCL11A-10158	-	GGAGAGGGGCCGCGGCGACG	20	15170
  BCL11A-12914	-	GGGAGAGGGGCCGCGGCGACG	21	15171
  BCL11A-12915	-	CGGGAGAGGGGCCGCGGCGACG	22	15172
  BCL11A-12916	-	UCGGGAGAGGGGCCGCGGCGACG	23	15173
  BCL11A-12917	-	GUCGGGAGAGGGGCCGCGGCGACG	24	15174
  BCL11A-12918	-	GAAGUGGGUGUGCGUACG	18	15175
  BCL11A-12919	-	GGAAGUGGGUGUGCGUACG	19	15176
  BCL11A-12920	-	GGGAAGUGGGUGUGCGUACG	20	15177
  BCL11A-12921	-	GGGGAAGUGGGUGUGCGUACG	21	15178
  BCL11A-12922	-	AGGGGAAGUGGGUGUGCGUACG	22	15179
  BCL11A-12923	-	GAGGGGAAGUGGGUGUGCGUACG	23	15180
  BCL11A-12924	-	GGAGGGGAAGUGGGUGUGCGUACG	24	15181
  BCL11A-12925	-	UCUAAAAAACGAUUCCCG	18	15182
  BCL11A-12926	-	GUCUAAAAAACGAUUCCCG	19	15183
  BCL11A-10164	-	AGUCUAAAAAACGAUUCCCG	20	15184
  BCL11A-12927	-	AAGUCUAAAAAACGAUUCCCG	21	15185
  BCL11A-12928	-	CAAGUCUAAAAAACGAUUCCCG	22	15186
  BCL11A-12929	-	ACAAGUCUAAAAAACGAUUCCCG	23	15187
  BCL11A-12930	-	UACAAGUCUAAAAAACGAUUCCCG	24	15188
  BCL11A-12931	-	CGGCGACGGGGAGAGCCG	18	15189
  BCL11A-12932	-	GCGGCGACGGGGAGAGCCG	19	15190
  BCL11A-10166	-	CGCGGCGACGGGGAGAGCCG	20	15191
  BCL11A-12933	-	CCGCGGCGACGGGGAGAGCCG	21	15192
  BCL11A-12934	-	GCCGCGGCGACGGGGAGAGCCG	22	15193
  BCL11A-12935	-	GGCCGCGGCGACGGGGAGAGCCG	23	15194
  BCL11A-12936	-	GGGCCGCGGCGACGGGGAGAGCCG	24	15195
  BCL11A-12937	-	CCCUGGCGUCCACACGCG	18	15196
  BCL11A-12938	-	CCCCUGGCGUCCACACGCG	19	15197
  BCL11A-10175	-	GCCCCUGGCGUCCACACGCG	20	15198
  BCL11A-12939	-	GGCCCCUGGCGUCCACACGCG	21	15199
  BCL11A-12940	-	CGGCCCCUGGCGUCCACACGCG	22	15200
  BCL11A-12941	-	UCGGCCCCUGGCGUCCACACGCG	23	15201
  BCL11A-12942	-	UUCGGCCCCUGGCGUCCACACGCG	24	15202
  BCL11A-12943	-	GGGAGAGGGGCCGCGGCG	18	15203
  BCL11A-12944	-	CGGGAGAGGGGCCGCGGCG	19	15204
  BCL11A-12945	-	UCGGGAGAGGGGCCGCGGCG	20	15205
  BCL11A-12946	-	GUCGGGAGAGGGGCCGCGGCG	21	15206
  BCL11A-12947	-	AGUCGGGAGAGGGGCCGCGGCG	22	15207
  BCL11A-12948	-	GAGUCGGGAGAGGGGCCGCGGCG	23	15208
  BCL11A-12949	-	GGAGUCGGGAGAGGGGCCGCGGCG	24	15209
  BCL11A-12950	-	GGAGCGAGCGCGGCGGCG	18	15210
  BCL11A-12951	-	GGGAGCGAGCGCGGCGGCG	19	15211
  BCL11A-12952	-	GGGGAGCGAGCGCGGCGGCG	20	15212
  BCL11A-12953	-	CGGGGAGCGAGCGCGGCGGCG	21	15213
  BCL11A-12954	-	GCGGGGAGCGAGCGCGGCGGCG	22	15214
  BCL11A-12955	-	CGCGGGGAGCGAGCGCGGCGGCG	23	15215
  BCL11A-12956	-	ACGCGGGGAGCGAGCGCGGCGGCG	24	15216
  BCL11A-12957	-	GCGAGCGCGGCGGCGGCG	18	15217
  BCL11A-12958	-	AGCGAGCGCGGCGGCGGCG	19	15218
  BCL11A-10179	-	GAGCGAGCGCGGCGGCGGCG	20	15219
  BCL11A-12959	-	GGAGCGAGCGCGGCGGCGGCG	21	15220
  BCL11A-12960	-	GGGAGCGAGCGCGGCGGCGGCG	22	15221
  BCL11A-12961	-	GGGGAGCGAGCGCGGCGGCGGCG	23	15222
  BCL11A-12962	-	CGGGGAGCGAGCGCGGCGGCGGCG	24	15223
  BCL11A-12963	-	GCCGUGGGACCGGGAAGG	18	15224
  BCL11A-12964	-	AGCCGUGGGACCGGGAAGG	19	15225
  BCL11A-12965	-	GAGCCGUGGGACCGGGAAGG	20	15226
  BCL11A-12966	-	AGAGCCGUGGGACCGGGAAGG	21	15227
  BCL11A-12967	-	GAGAGCCGUGGGACCGGGAAGG	22	15228
  BCL11A-12968	-	GGAGAGCCGUGGGACCGGGAAGG	23	15229
  BCL11A-12969	-	GGGAGAGCCGUGGGACCGGGAAGG	24	15230
  BCL11A-12970	-	AGAAAAUGGGGGGGUAGG	18	15231
  BCL11A-12971	-	AAGAAAAUGGGGGGGUAGG	19	15232
  BCL11A-12972	-	UAAGAAAAUGGGGGGGUAGG	20	15233
  BCL11A-12973	-	GUAAGAAAAUGGGGGGGUAGG	21	15234
  BCL11A-12974	-	CGUAAGAAAAUGGGGGGGUAGG	22	15235
  BCL11A-12975	-	CCGUAAGAAAAUGGGGGGGUAGG	23	15236
  BCL11A-12976	-	ACCGUAAGAAAAUGGGGGGGUAGG	24	15237
  BCL11A-12977	-	AAGUGGGUGUGCGUACGG	18	15238
  BCL11A-12978	-	GAAGUGGGUGUGCGUACGG	19	15239
  BCL11A-10191	-	GGAAGUGGGUGUGCGUACGG	20	15240
  BCL11A-12979	-	GGGAAGUGGGUGUGCGUACGG	21	15241
  BCL11A-12980	-	GGGGAAGUGGGUGUGCGUACGG	22	15242
  BCL11A-12981	-	AGGGGAAGUGGGUGUGCGUACGG	23	15243
  BCL11A-12982	-	GAGGGGAAGUGGGUGUGCGUACGG	24	15244
  BCL11A-12983	-	CGGUCAAGUGUGCAGCGG	18	15245
  BCL11A-12984	-	ACGGUCAAGUGUGCAGCGG	19	15246
  BCL11A-12985	-	CACGGUCAAGUGUGCAGCGG	20	15247
  BCL11A-12986	-	UCACGGUCAAGUGUGCAGCGG	21	15248
  BCL11A-12987	-	CUCACGGUCAAGUGUGCAGCGG	22	15249
  BCL11A-12988	-	GCUCACGGUCAAGUGUGCAGCGG	23	15250
  BCL11A-12989	-	CGCUCACGGUCAAGUGUGCAGCGG	24	15251
  BCL11A-12990	-	GAGCGAGCGCGGCGGCGG	18	15252
  BCL11A-12991	-	GGAGCGAGCGCGGCGGCGG	19	15253
  BCL11A-10196	-	GGGAGCGAGCGCGGCGGCGG	20	15254
  BCL11A-12992	-	GGGGAGCGAGCGCGGCGGCGG	21	15255
  BCL11A-12993	-	CGGGGAGCGAGCGCGGCGGCGG	22	15256
  BCL11A-12994	-	GCGGGGAGCGAGCGCGGCGGCGG	23	15257
  BCL11A-12995	-	CGCGGGGAGCGAGCGCGGCGGCGG	24	15258
  BCL11A-12996	-	CUGAGUCCGCGGAGUCGG	18	15259
  BCL11A-12997	-	CCUGAGUCCGCGGAGUCGG	19	15260
  BCL11A-12998	-	UCCUGAGUCCGCGGAGUCGG	20	15261
  BCL11A-12999	-	CUCCUGAGUCCGCGGAGUCGG	21	15262
  BCL11A-13000	-	GCUCCUGAGUCCGCGGAGUCGG	22	15263
  BCL11A-13001	-	CGCUCCUGAGUCCGCGGAGUCGG	23	15264
  BCL11A-13002	-	GCGCUCCUGAGUCCGCGGAGUCGG	24	15265
  BCL11A-13003	-	gaaaauggggggguaggg	18	15266
  BCL11A-13004	-	AGAAAAUGGGGGGGUAGGG	19	15267
  BCL11A-10200	-	AAGAAAAUGGGGGGGUAGGG	20	15268
  BCL11A-13005	-	UAAGAAAAUGGGGGGGUAGGG	21	15269
  BCL11A-13006	-	GUAAGAAAAUGGGGGGGUAGGG	22	15270
  BCL11A-13007	-	CGUAAGAAAAUGGGGGGGUAGGG	23	15271
  BCL11A-13008	-	CCGUAAGAAAAUGGGGGGGUAGGG	24	15272
  BCL11A-13009	-	AGGGGCCGCGGCGACGGG	18	15273
  BCL11A-13010	-	GAGGGGCCGCGGCGACGGG	19	15274
  BCL11A-13011	-	AGAGGGGCCGCGGCGACGGG	20	15275
  BCL11A-13012	-	GAGAGGGGCCGCGGCGACGGG	21	15276
  BCL11A-13013	-	GGAGAGGGGCCGCGGCGACGGG	22	15277
  BCL11A-13014	-	GGGAGAGGGGCCGCGGCGACGGG	23	15278
  BCL11A-13015	-	CGGGAGAGGGGCCGCGGCGACGGG	24	15279
  BCL11A-13016	-	GAGAGCCGUGGGACCGGG	18	15280
  BCL11A-13017	-	GGAGAGCCGUGGGACCGGG	19	15281
  BCL11A-13018	-	GGGAGAGCCGUGGGACCGGG	20	15282
  BCL11A-13019	-	GGGGAGAGCCGUGGGACCGGG	21	15283
  BCL11A-13020	-	CGGGGAGAGCCGUGGGACCGGG	22	15284
  BCL11A-13021	-	ACGGGGAGAGCCGUGGGACCGGG	23	15285
  BCL11A-13022	-	GACGGGGAGAGCCGUGGGACCGGG	24	15286
  BCL11A-13023	-	UAAAAAACGAUUCCCGGG	18	15287
  BCL11A-13024	-	CUAAAAAACGAUUCCCGGG	19	15288
  BCL11A-13025	-	UCUAAAAAACGAUUCCCGGG	20	15289
  BCL11A-13026	-	GUCUAAAAAACGAUUCCCGGG	21	15290
  BCL11A-13027	-	AGUCUAAAAAACGAUUCCCGGG	22	15291
  BCL11A-13028	-	AAGUCUAAAAAACGAUUCCCGGG	23	15292
  BCL11A-13029	-	CAAGUCUAAAAAACGAUUCCCGGG	24	15293
  BCL11A-13030	-	GGUCAAGUGUGCAGCGGG	18	15294
  BCL11A-13031	-	CGGUCAAGUGUGCAGCGGG	19	15295
  BCL11A-10202	-	ACGGUCAAGUGUGCAGCGGG	20	15296
  BCL11A-13032	-	CACGGUCAAGUGUGCAGCGGG	21	15297
  BCL11A-13033	-	UCACGGUCAAGUGUGCAGCGGG	22	15298
  BCL11A-13034	-	CUCACGGUCAAGUGUGCAGCGGG	23	15299
  BCL11A-13035	-	GCUCACGGUCAAGUGUGCAGCGGG	24	15300
  BCL11A-13036	-	GAGCGCGGCGGCGGCGGG	18	15301
  BCL11A-13037	-	CGAGCGCGGCGGCGGCGGG	19	15302
  BCL11A-13038	-	GCGAGCGCGGCGGCGGCGGG	20	15303
  BCL11A-13039	-	AGCGAGCGCGGCGGCGGCGGG	21	15304
  BCL11A-13040	-	GAGCGAGCGCGGCGGCGGCGGG	22	15305
  BCL11A-13041	-	GGAGCGAGCGCGGCGGCGGCGGG	23	15306
  BCL11A-13042	-	GGGAGCGAGCGCGGCGGCGGCGGG	24	15307
  BCL11A-13043	-	AGCGCGGCGGCGGCGGGG	18	15308
  BCL11A-13044	-	GAGCGCGGCGGCGGCGGGG	19	15309
  BCL11A-10206	-	CGAGCGCGGCGGCGGCGGGG	20	15310
  BCL11A-13045	-	GCGAGCGCGGCGGCGGCGGGG	21	15311
  BCL11A-13046	-	AGCGAGCGCGGCGGCGGCGGGG	22	15312
  BCL11A-13047	-	GAGCGAGCGCGGCGGCGGCGGGG	23	15313
  BCL11A-13048	-	GGAGCGAGCGCGGCGGCGGCGGGG	24	15314
  BCL11A-13049	-	CGUAAGAAAAUGGGGGGG	18	15315
  BCL11A-13050	-	CCGUAAGAAAAUGGGGGGG	19	15316
  BCL11A-13051	-	ACCGUAAGAAAAUGGGGGGG	20	15317
  BCL11A-13052	-	CACCGUAAGAAAAUGGGGGGG	21	15318
  BCL11A-13053	-	UCACCGUAAGAAAAUGGGGGGG	22	15319
  BCL11A-13054	-	CUCACCGUAAGAAAAUGGGGGGG	23	15320
  BCL11A-13055	-	ACUCACCGUAAGAAAAUGGGGGGG	24	15321
  BCL11A-13056	-	CACAUGCAAACCUGGGGG	18	15322
  BCL11A-13057	-	UCACAUGCAAACCUGGGGG	19	15323
  BCL11A-10210	-	CUCACAUGCAAACCUGGGGG	20	15324
  BCL11A-13058	-	ACUCACAUGCAAACCUGGGGG	21	15325
  BCL11A-13059	-	AACUCACAUGCAAACCUGGGGG	22	15326
  BCL11A-13060	-	CAACUCACAUGCAAACCUGGGGG	23	15327
  BCL11A-13061	-	ACAACUCACAUGCAAACCUGGGGG	24	15328
  BCL11A-13062	-	UCACAUGCAAACCUGGGG	18	15329
  BCL11A-13063	-	CUCACAUGCAAACCUGGGG	19	15330
  BCL11A-13064	-	ACUCACAUGCAAACCUGGGG	20	15331
  BCL11A-13065	-	AACUCACAUGCAAACCUGGGG	21	15332
  BCL11A-13066	-	CAACUCACAUGCAAACCUGGGG	22	15333
  BCL11A-13067	-	ACAACUCACAUGCAAACCUGGGG	23	15334
  BCL11A-13068	-	AACAACUCACAUGCAAACCUGGGG	24	15335
  BCL11A-11486	-	GAGUCCGCGUGUGUGGGG	18	15336
  BCL11A-11487	-	AGAGUCCGCGUGUGUGGGG	19	15337
  BCL11A-9577	-	UAGAGUCCGCGUGUGUGGGG	20	15338
  BCL11A-11488	-	UUAGAGUCCGCGUGUGUGGGG	21	15339
  BCL11A-11489	-	UUUAGAGUCCGCGUGUGUGGGG	22	15340
  BCL11A-11490	-	UUUUAGAGUCCGCGUGUGUGGGG	23	15341
  BCL11A-11491	-	AUUUUAGAGUCCGCGUGUGUGGGG	24	15342
  BCL11A-11492	-	AGAGUCCGCGUGUGUGGG	18	15343
  BCL11A-11493	-	UAGAGUCCGCGUGUGUGGG	19	15344
  BCL11A-9769	-	UUAGAGUCCGCGUGUGUGGG	20	15345
  BCL11A-11494	-	UUUAGAGUCCGCGUGUGUGGG	21	15346
  BCL11A-11495	-	UUUUAGAGUCCGCGUGUGUGGG	22	15347
  BCL11A-11496	-	AUUUUAGAGUCCGCGUGUGUGGG	23	15348
  BCL11A-11497	-	CAUUUUAGAGUCCGCGUGUGUGGG	24	15349
  BCL11A-13069	-	CCUGGGGGUGGGAGCUGG	18	15350
  BCL11A-13070	-	ACCUGGGGGUGGGAGCUGG	19	15351
  BCL11A-10217	-	AACCUGGGGGUGGGAGCUGG	20	15352
  BCL11A-13071	-	AAACCUGGGGGUGGGAGCUGG	21	15353
  BCL11A-13072	-	CAAACCUGGGGGUGGGAGCUGG	22	15354
  BCL11A-13073	-	GCAAACCUGGGGGUGGGAGCUGG	23	15355
  BCL11A-13074	-	UGCAAACCUGGGGGUGGGAGCUGG	24	15356
  BCL11A-11498	-	UAGAGUCCGCGUGUGUGG	18	15357
  BCL11A-11499	-	UUAGAGUCCGCGUGUGUGG	19	15358
  BCL11A-9578	-	UUUAGAGUCCGCGUGUGUGG	20	15359
  BCL11A-11500	-	UUUUAGAGUCCGCGUGUGUGG	21	15360
  BCL11A-11501	-	AUUUUAGAGUCCGCGUGUGUGG	22	15361
  BCL11A-11502	-	CAUUUUAGAGUCCGCGUGUGUGG	23	15362
  BCL11A-11503	-	UCAUUUUAGAGUCCGCGUGUGUGG	24	15363
  BCL11A-13075	-	ACUCACCGUAAGAAAAUG	18	15364
  BCL11A-13076	-	CACUCACCGUAAGAAAAUG	19	15365
  BCL11A-10221	-	CCACUCACCGUAAGAAAAUG	20	15366
  BCL11A-13077	-	CCCACUCACCGUAAGAAAAUG	21	15367
  BCL11A-13078	-	UCCCACUCACCGUAAGAAAAUG	22	15368
  BCL11A-13079	-	UUCCCACUCACCGUAAGAAAAUG	23	15369
  BCL11A-13080	-	CUUCCCACUCACCGUAAGAAAAUG	24	15370
  BCL11A-13081	-	AGUGAGAAAGUGGCACUG	18	15371
  BCL11A-13082	-	UAGUGAGAAAGUGGCACUG	19	15372
  BCL11A-10222	-	AUAGUGAGAAAGUGGCACUG	20	15373
  BCL11A-13083	-	AAUAGUGAGAAAGUGGCACUG	21	15374
  BCL11A-13084	-	CAAUAGUGAGAAAGUGGCACUG	22	15375
  BCL11A-13085	-	ACAAUAGUGAGAAAGUGGCACUG	23	15376
  BCL11A-13086	-	CACAAUAGUGAGAAAGUGGCACUG	24	15377
  BCL11A-13087	-	ACCUGGGGGUGGGAGCUG	18	15378
  BCL11A-13088	-	AACCUGGGGGUGGGAGCUG	19	15379
  BCL11A-13089	-	AAACCUGGGGGUGGGAGCUG	20	15380
  BCL11A-13090	-	CAAACCUGGGGGUGGGAGCUG	21	15381
  BCL11A-13091	-	GCAAACCUGGGGGUGGGAGCUG	22	15382
  BCL11A-13092	-	UGCAAACCUGGGGGUGGGAGCUG	23	15383
  BCL11A-13093	-	AUGCAAACCUGGGGGUGGGAGCUG	24	15384
  BCL11A-13094	-	ACCUCCCCUCGCCCGCUG	18	15385
  BCL11A-13095	-	CACCUCCCCUCGCCCGCUG	19	15386
  BCL11A-10224	-	CCACCUCCCCUCGCCCGCUG	20	15387
  BCL11A-13096	-	CCCACCUCCCCUCGCCCGCUG	21	15388
  BCL11A-13097	-	UCCCACCUCCCCUCGCCCGCUG	22	15389
  BCL11A-13098	-	CUCCCACCUCCCCUCGCCCGCUG	23	15390
  BCL11A-13099	-	CCUCCCACCUCCCCUCGCCCGCUG	24	15391
  BCL11A-13100	-	UGGGGGUGGGAGCUGGUG	18	15392
  BCL11A-13101	-	CUGGGGGUGGGAGCUGGUG	19	15393
  BCL11A-10228	-	CCUGGGGGUGGGAGCUGGUG	20	15394
  BCL11A-13102	-	ACCUGGGGGUGGGAGCUGGUG	21	15395
  BCL11A-13103	-	AACCUGGGGGUGGGAGCUGGUG	22	15396
  BCL11A-13104	-	AAACCUGGGGGUGGGAGCUGGUG	23	15397
  BCL11A-13105	-	CAAACCUGGGGGUGGGAGCUGGUG	24	15398
  BCL11A-11518	-	UUUUAGAGUCCGCGUGUG	18	15399
  BCL11A-11519	-	AUUUUAGAGUCCGCGUGUG	19	15400
  BCL11A-9581	-	CAUUUUAGAGUCCGCGUGUG	20	15401
  BCL11A-11520	-	UCAUUUUAGAGUCCGCGUGUG	21	15402
  BCL11A-11521	-	UUCAUUUUAGAGUCCGCGUGUG	22	15403
  BCL11A-11522	-	UUUCAUUUUAGAGUCCGCGUGUG	23	15404
  BCL11A-11523	-	CUUUCAUUUUAGAGUCCGCGUGUG	24	15405
  BCL11A-11524	-	UUAGAGUCCGCGUGUGUG	18	15406
  BCL11A-11525	-	UUUAGAGUCCGCGUGUGUG	19	15407
  BCL11A-9776	-	UUUUAGAGUCCGCGUGUGUG	20	15408
  BCL11A-11526	-	AUUUUAGAGUCCGCGUGUGUG	21	15409
  BCL11A-11527	-	CAUUUUAGAGUCCGCGUGUGUG	22	15410
  BCL11A-11528	-	UCAUUUUAGAGUCCGCGUGUGUG	23	15411
  BCL11A-11529	-	UUCAUUUUAGAGUCCGCGUGUGUG	24	15412
  BCL11A-13106	-	CACUCACCGUAAGAAAAU	18	15413
  BCL11A-13107	-	CCACUCACCGUAAGAAAAU	19	15414
  BCL11A-10232	-	CCCACUCACCGUAAGAAAAU	20	15415
  BCL11A-13108	-	UCCCACUCACCGUAAGAAAAU	21	15416
  BCL11A-13109	-	UUCCCACUCACCGUAAGAAAAU	22	15417
  BCL11A-13110	-	CUUCCCACUCACCGUAAGAAAAU	23	15418
  BCL11A-13111	-	GCUUCCCACUCACCGUAAGAAAAU	24	15419
  BCL11A-13112	-	CGCUGCGGAGCUGUAACU	18	15420
  BCL11A-13113	-	CCGCUGCGGAGCUGUAACU	19	15421
  BCL11A-10233	-	CCCGCUGCGGAGCUGUAACU	20	15422
  BCL11A-13114	-	GCCCGCUGCGGAGCUGUAACU	21	15423
  BCL11A-13115	-	CGCCCGCUGCGGAGCUGUAACU	22	15424
  BCL11A-13116	-	UCGCCCGCUGCGGAGCUGUAACU	23	15425
  BCL11A-13117	-	CUCGCCCGCUGCGGAGCUGUAACU	24	15426
  BCL11A-13118	-	UAGUGAGAAAGUGGCACU	18	15427
  BCL11A-13119	-	AUAGUGAGAAAGUGGCACU	19	15428
  BCL11A-13120	-	AAUAGUGAGAAAGUGGCACU	20	15429
  BCL11A-13121	-	CAAUAGUGAGAAAGUGGCACU	21	15430
  BCL11A-13122	-	ACAAUAGUGAGAAAGUGGCACU	22	15431
  BCL11A-13123	-	CACAAUAGUGAGAAAGUGGCACU	23	15432
  BCL11A-13124	-	CCACAAUAGUGAGAAAGUGGCACU	24	15433
  BCL11A-13125	-	CGGUCCCUGGCUCGGCCU	18	15434
  BCL11A-13126	-	CCGGUCCCUGGCUCGGCCU	19	15435
  BCL11A-10237	-	CCCGGUCCCUGGCUCGGCCU	20	15436
  BCL11A-13127	-	CACCUCCCCUCGCCCGCU	18	15437
  BCL11A-13128	-	CCACCUCCCCUCGCCCGCU	19	15438
  BCL11A-13129	-	CCCACCUCCCCUCGCCCGCU	20	15439
  BCL11A-13130	-	UCCCACCUCCCCUCGCCCGCU	21	15440
  BCL11A-13131	-	CUCCCACCUCCCCUCGCCCGCU	22	15441
  BCL11A-13132	-	CCUCCCACCUCCCCUCGCCCGCU	23	15442
  BCL11A-13133	-	CCCUCCCACCUCCCCUCGCCCGCU	24	15443
  BCL11A-13134	-	CGAGCGCAGCCGCGGGCU	18	15444
  BCL11A-13135	-	CCGAGCGCAGCCGCGGGCU	19	15445
  BCL11A-10241	-	CCCGAGCGCAGCCGCGGGCU	20	15446
  BCL11A-13136	-	UCCCGAGCGCAGCCGCGGGCU	21	15447
  BCL11A-13137	-	UUCCCGAGCGCAGCCGCGGGCU	22	15448
  BCL11A-13138	-	UUUCCCGAGCGCAGCCGCGGGCU	23	15449
  BCL11A-13139	-	GUUUCCCGAGCGCAGCCGCGGGCU	24	15450
  BCL11A-13140	-	CUCCUGAGUCCGCGGAGU	18	15451
  BCL11A-13141	-	GCUCCUGAGUCCGCGGAGU	19	15452
  BCL11A-10243	-	CGCUCCUGAGUCCGCGGAGU	20	15453
  BCL11A-13142	-	GCGCUCCUGAGUCCGCGGAGU	21	15454
  BCL11A-13143	-	GGCGCUCCUGAGUCCGCGGAGU	22	15455
  BCL11A-13144	-	CGGCGCUCCUGAGUCCGCGGAGU	23	15456
  BCL11A-13145	-	CCGGCGCUCCUGAGUCCGCGGAGU	24	15457
  BCL11A-13146	-	AGUCAUCCCCACAAUAGU	18	15458
  BCL11A-13147	-	UAGUCAUCCCCACAAUAGU	19	15459
  BCL11A-13148	-	GUAGUCAUCCCCACAAUAGU	20	15460
  BCL11A-13149	-	AGUAGUCAUCCCCACAAUAGU	21	15461
  BCL11A-13150	-	AAGUAGUCAUCCCCACAAUAGU	22	15462
  BCL11A-13151	-	AAAGUAGUCAUCCCCACAAUAGU	23	15463
  BCL11A-13152	-	GAAAGUAGUCAUCCCCACAAUAGU	24	15464
  BCL11A-13153	-	UUGCUUCCCACUCACCGU	18	15465
  BCL11A-13154	-	GUUGCUUCCCACUCACCGU	19	15466
  BCL11A-13155	-	GGUUGCUUCCCACUCACCGU	20	15467
  BCL11A-13156	-	AGGUUGCUUCCCACUCACCGU	21	15468
  BCL11A-13157	-	GAGGUUGCUUCCCACUCACCGU	22	15469
  BCL11A-13158	-	GGAGGUUGCUUCCCACUCACCGU	23	15470
  BCL11A-13159	-	GGGAGGUUGCUUCCCACUCACCGU	24	15471
  BCL11A-13160	-	GGGGAAGUGGGUGUGCGU	18	15472
  BCL11A-13161	-	AGGGGAAGUGGGUGUGCGU	19	15473
  BCL11A-13162	-	GAGGGGAAGUGGGUGUGCGU	20	15474
  BCL11A-13163	-	GGAGGGGAAGUGGGUGUGCGU	21	15475
  BCL11A-13164	-	GGGAGGGGAAGUGGGUGUGCGU	22	15476
  BCL11A-13165	-	GGGGAGGGGAAGUGGGUGUGCGU	23	15477
  BCL11A-13166	-	CGGGGAGGGGAAGUGGGUGUGCGU	24	15478
  BCL11A-13167	-	GUAAGAAAAUGGGGGGGU	18	15479
  BCL11A-13168	-	CGUAAGAAAAUGGGGGGGU	19	15480
  BCL11A-10248	-	CCGUAAGAAAAUGGGGGGGU	20	15481
  BCL11A-13169	-	ACCGUAAGAAAAUGGGGGGGU	21	15482
  BCL11A-13170	-	CACCGUAAGAAAAUGGGGGGGU	22	15483
  BCL11A-13171	-	UCACCGUAAGAAAAUGGGGGGGU	23	15484
  BCL11A-13172	-	CUCACCGUAAGAAAAUGGGGGGGU	24	15485
  BCL11A-13173	-	ACAUGCAAACCUGGGGGU	18	15486
  BCL11A-13174	-	CACAUGCAAACCUGGGGGU	19	15487
  BCL11A-10249	-	UCACAUGCAAACCUGGGGGU	20	15488
  BCL11A-13175	-	CUCACAUGCAAACCUGGGGGU	21	15489
  BCL11A-13176	-	ACUCACAUGCAAACCUGGGGGU	22	15490
  BCL11A-13177	-	AACUCACAUGCAAACCUGGGGGU	23	15491
  BCL11A-13178	-	CAACUCACAUGCAAACCUGGGGGU	24	15492
  BCL11A-13179	-	CUGGGGGUGGGAGCUGGU	18	15493
  BCL11A-13180	-	CCUGGGGGUGGGAGCUGGU	19	15494
  BCL11A-10250	-	ACCUGGGGGUGGGAGCUGGU	20	15495
  BCL11A-13181	-	AACCUGGGGGUGGGAGCUGGU	21	15496
  BCL11A-13182	-	AAACCUGGGGGUGGGAGCUGGU	22	15497
  BCL11A-13183	-	CAAACCUGGGGGUGGGAGCUGGU	23	15498
  BCL11A-13184	-	GCAAACCUGGGGGUGGGAGCUGGU	24	15499
  BCL11A-11572	-	AUUUUAGAGUCCGCGUGU	18	15500
  BCL11A-11573	-	CAUUUUAGAGUCCGCGUGU	19	15501
  BCL11A-11574	-	UCAUUUUAGAGUCCGCGUGU	20	15502
  BCL11A-11575	-	UUCAUUUUAGAGUCCGCGUGU	21	15503
  BCL11A-11576	-	UUUCAUUUUAGAGUCCGCGUGU	22	15504
  BCL11A-11577	-	CUUUCAUUUUAGAGUCCGCGUGU	23	15505
  BCL11A-11578	-	UCUUUCAUUUUAGAGUCCGCGUGU	24	15506
  BCL11A-13185	-	GCGUACGGAGGAGGGUGU	18	15507
  BCL11A-13186	-	UGCGUACGGAGGAGGGUGU	19	15508
  BCL11A-13187	-	GUGCGUACGGAGGAGGGUGU	20	15509
  BCL11A-13188	-	UGUGCGUACGGAGGAGGGUGU	21	15510
  BCL11A-13189	-	GUGUGCGUACGGAGGAGGGUGU	22	15511
  BCL11A-13190	-	GGUGUGCGUACGGAGGAGGGUGU	23	15512
  BCL11A-13191	-	GGGUGUGCGUACGGAGGAGGGUGU	24	15513
  BCL11A-11579	-	UUUAGAGUCCGCGUGUGU	18	15514
  BCL11A-11580	-	UUUUAGAGUCCGCGUGUGU	19	15515
  BCL11A-9586	-	AUUUUAGAGUCCGCGUGUGU	20	15516
  BCL11A-11581	-	CAUUUUAGAGUCCGCGUGUGU	21	15517
  BCL11A-11582	-	UCAUUUUAGAGUCCGCGUGUGU	22	15518
  BCL11A-11583	-	UUCAUUUUAGAGUCCGCGUGUGU	23	15519
  BCL11A-11584	-	UUUCAUUUUAGAGUCCGCGUGUGU	24	15520
  BCL11A-13192	-	GACUUGGGCGCUGCCCUU	18	15521
  BCL11A-13193	-	AGACUUGGGCGCUGCCCUU	19	15522
  BCL11A-13194	-	GAGACUUGGGCGCUGCCCUU	20	15523
  BCL11A-13195	-	GGAGACUUGGGCGCUGCCCUU	21	15524
  BCL11A-13196	-	UGGAGACUUGGGCGCUGCCCUU	22	15525
  BCL11A-13197	-	CUGGAGACUUGGGCGCUGCCCUU	23	15526
  BCL11A-13198	-	CCUGGAGACUUGGGCGCUGCCCUU	24	15527
  BCL11A-13199	-	GGUCCCUGGCUCGGCCUU	18	15528
  BCL11A-13200	-	CGGUCCCUGGCUCGGCCUU	19	15529
  BCL11A-10256	-	CCGGUCCCUGGCUCGGCCUU	20	15530
  BCL11A-13201	-	AAGAGGUGAGACUGGCUU	18	15531
  BCL11A-13202	-	AAAGAGGUGAGACUGGCUU	19	15532
  BCL11A-13203	-	AAAAGAGGUGAGACUGGCUU	20	15533
  BCL11A-13204	-	GAAAAGAGGUGAGACUGGCUU	21	15534
  BCL11A-13205	-	AGAAAAGAGGUGAGACUGGCUU	22	15535
  BCL11A-13206	-	GAGAAAAGAGGUGAGACUGGCUU	23	15536
  BCL11A-13207	-	GGAGAAAAGAGGUGAGACUGGCUU	24	15537
  BCL11A-13208	-	AUGAACAAUGCUAAGGUU	18	15538
  BCL11A-13209	-	AAUGAACAAUGCUAAGGUU	19	15539
  BCL11A-13210	-	UAAUGAACAAUGCUAAGGUU	20	15540
  BCL11A-13211	-	AUAAUGAACAAUGCUAAGGUU	21	15541
  BCL11A-13212	-	AAUAAUGAACAAUGCUAAGGUU	22	15542
  BCL11A-13213	-	AAAUAAUGAACAAUGCUAAGGUU	23	15543
  BCL11A-13214	-	AAAAUAAUGAACAAUGCUAAGGUU	24	15544
  BCL11A-13215	-	GCCGCUUUAUUUCUCUUU	18	15545
  BCL11A-13216	-	CGCCGCUUUAUUUCUCUUU	19	15546
  BCL11A-13217	-	CCGCCGCUUUAUUUCUCUUU	20	15547
  BCL11A-13218	-	UCCGCCGCUUUAUUUCUCUUU	21	15548
  BCL11A-13219	-	UUCCGCCGCUUUAUUUCUCUUU	22	15549
  BCL11A-13220	-	UUUCCGCCGCUUUAUUUCUCUUU	23	15550
  BCL11A-13221	-	CUUUCCGCCGCUUUAUUUCUCUUU	24	15551

• Table 20A provides exemplary targeting domains for knocking down the BCL11A 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 BCL17A gene (e.g., reduce or eliminate BCL11A gene expression, BCL11A protein function, or the level of BCL15A protein). One or more gRNA may be used to target an eiCas9 to the promoter region of the BCL11A gene.

• TABLE 20A
  1st Tier

  			Target
  	DNA		Site	SEQ ID
  gRNA Name	Strand	Targeting Domain	Length	NO:
  BCL11A-13222	+	ACACACCCCUCUCUCCC	17	15552
  BCL11A-9477	+	CUUACGCGAGAAUUCCC	17	15553
  BCL11A-13223	+	CCCUCUCUCCCCCUCGC	17	15554
  BCL11A-13224	+	UCUAGUCCUGCGCGCUC	17	15555
  BCL11A-9638	-	UUGAACUUGCAGCUCAG	17	15556
  BCL11A-9482	+	UUAAGUGCUGGGGUUUG	17	15557
  BCL11A-13225	+	CACGCGGACUCUAAAAU	17	15558
  BCL11A-13226	+	AAUUGUGGGAGAGCCGU	17	15559
  BCL11A-13227	-	GAUGUGUGUCCAUUGGU	17	15560
  BCL11A-13228	+	UGCACACACCCCUCUCUCCC	20	15561
  BCL11A-9487	+	UUACUUACGCGAGAAUUCCC	20	15562
  BCL11A-13229	+	CACCCCUCUCUCCCCCUCGC	20	15563
  BCL11A-13230	+	GCUUCUAGUCCUGCGCGCUC	20	15564
  BCL11A-9738	-	CACUUGAACUUGCAGCUCAG	20	15565
  BCL11A-9491	+	UGCUUAAGUGCUGGGGUUUG	20	15566
  BCL11A-13231	+	AUGAAUUGUGGGAGAGCCGU	20	15567
  BCL11A-11567	-	CCUGAUGUGUGUCCAUUGGU	20	15568

• Table 20B provides exemplary targeting domains for knocking down the BCL11A 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 BCL11A gene (e.g., reduce or eliminate BCL11A gene expression, BCL11A protein function, or the level of BCL11A protein). One or more gRNA may be used to target an eiCas9 to the promoter region of the BCL11A gene.

• TABLE 20B
  2nd Tier

  	DNA		Target Site	SEQ
  gRNA Name	Strand	Targeting Domain	Length	ID NO:
  BCL11A-13232	-	CCCUCCCCGCACUGGCC	17	15569
  BCL11A-13233	-	UUUUUUUUUUUUUUUUU	17	15570
  BCL11A-13234	-	UCCCCCUCCCCGCACUGGCC	20	15571
  BCL11A-13235	+	ACACACGCGGACUCUAAAAU	20	15572
  BCL11A-13236	-	UUUUUUUUUUUUUUUUUUUU	20	15573

• Table 20C provides exemplary targeting domains for knocking down the BCL11A 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 1 kb 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 BCL11A gene (e.g., reduce or eliminate BCL11A gene expression, BCL15A protein function, or the level of BCL11A protein). One or more gRNA may be used to target an eiCas9 to the promoter region of the BCL11A gene.

• TABLE 20C
  3rd Tier

  	DNA		Target Site	SEQ ID
  gRNA Name	Strand	Targeting Domain	Length	NO:
  BCL11A-13237	-	GUGAGUACAAGUCUAAA	17	15574
  BCL11A-13238	-	GCUGGUGGGGAAAGGGA	17	15575
  BCL11A-13239	-	GUCCGGGAGCAACUCUA	17	15576
  BCL11A-13240	-	CCUUUUGUGCCGGCUCC	17	15577
  BCL11A-13241	-	ACCUGGCUUCCCUCCGC	17	15578
  BCL11A-9896	-	GCUCAGCUCUCAACUUC	17	15579
  BCL11A-13242	-	UCCUCUUUCCUCCUUUC	17	15580
  BCL11A-13243	-	GGGAGAAAAGAGGUGAG	17	15581
  BCL11A-13244	-	CAGCCCUCCAAACUUAG	17	15582
  BCL11A-13245	-	CUUUUCGAAAAGGAAUG	17	15583
  BCL11A-13225	+	CACGCGGACUCUAAAAU	17	15584
  BCL11A-10006	-	GAGCGCAGCCGCGGGCU	17	15585
  BCL11A-13246	-	GGAGUGAGUACAAGUCUAAA	20	15586
  BCL11A-13247	-	GGAGCUGGUGGGGAAAGGGA	20	15587
  BCL11A-13248	-	GGUGUCCGGGAGCAACUCUA	20	15588
  BCL11A-13249	-	CUGCCUUUUGUGCCGGCUCC	20	15589
  BCL11A-13250	-	UCUACCUGGCUUCCCUCCGC	20	15590
  BCL11A-10131	-	GAGGCUCAGCUCUCAACUUC	20	15591
  BCL11A-13251	-	uccuccucuuuccuccuuuc	20	15592
  BCL11A-13252	-	CCGGGGAGAAAAGAGGUGAG	20	15593
  BCL11A-13253	-	CCGCAGCCCUCCAAACUUAG	20	15594
  BCL11A-13254	-	UCUCUUUUCGAAAAGGAAUG	20	15595
  BCL11A-13235	+	ACACACGCGGACUCUAAAAU	20	15596
  BCL11A-10241	-	CCCGAGCGCAGCCGCGGGCU	20	15597

• Table 21A provides exemplary targeting domains for removing (e.g., deleting) the enhancer region of the BCL11A gene selected according to the first tier parameters. The targeting domains bind within a region 5′ (51.5 to 51.7 kb downstream of TSS) or 3′ (65.1 to 65.3 kb downstream of TSS), and 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 21A
  1st Tier

  			Target
  	DNA		Site		SEQ ID
  gRNA Name	Strand	Targeting Domain	Length		5′ or 3′	NO:
  BCL11A-13255	+	GCACUAGGUGAAAUCUC	17	5′	15598
  BCL11A-13256	-	GAAAGCAGUGUAAGGCU	17	5′	15599
  BCL11A-13257	-	GUAAUUAAGAAAGCAGUGUA	20	5′	15600
  BCL11A-13258	+	GUUGCACUAGGUGAAAUCUC	20	5′	15601
  BCL11A-13259	-	GGCUGUUUUGGAAUGUAGAG	20	5′	15602
  BCL11A-13260	-	GGCUGUUUUUGGAUCUU	17	3′	15603
  BCL11A-13261	+	GUGCUACUUAUACAAUUCAC	20	3′	15604
  BCL11A-13262	+	GAAAAUACUUACUGUACUGC	20	3′	15605

• Table 21B provides exemplary targeting domains for removing (e.g., deleting) the enhancer region of the BCL11A gene selected according to the second tier parameters. The targeting domains bind within a region 5′ (51.5 to 51.7 kb downstream of TSS) or 3′ (65.1 to 65.3 kb 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 21B
  2nd Tier

  			Target
  	DNA		Site		SEQ ID
  gRNA Name	Strand	Targeting Domain	Length		5′ or 3′	NO:
  BCL11A-13263	-	AUUAAGAAAGCAGUGUA	17	5′	15606
  BCL11A-13264	+	AUUUUACUAGUGAAUUA	17	5′	15607
  BCL11A-13265	+	AUUUAAGACGGGAAAAC	17	5′	15608
  BCL11A-13266	-	AGAAAGCAGUGUAAGGC	17	5′	15609
  BCL11A-13267	-	UGUUUUGGAAUGUAGAG	17	5′	15610
  BCL11A-13268	+	ACAACUUGUGUUGCACU	17	5′	15611
  BCL11A-13269	+	UCUCACAUAAAAAUUUAAGA	20	5′	15612
  BCL11A-13270	-	UUGGAAUGUAGAGAGGCAGA	20	5′	15613
  BCL11A-13271	+	AUUAUUUUACUAGUGAAUUA	20	5′	15614
  BCL11A-13272	+	AAAAUUUAAGACGGGAAAAC	20	5′	15615
  BCL11A-13273	+	CUCACAUAAAAAUUUAAGAC	20	5′	15616
  BCL11A-13274	+	UACACAACUUGUGUUGCACU	20	5′	15617
  BCL11A-13275	-	UAAGAAAGCAGUGUAAGGCU	20	5′	15618
  BCL11A-13276	-	AUUAGAAUAAAAGGCUGUUU	20	5′	15619
  BCL11A-13277	-	UAUUUACAGCCAUAACA	17	3′	15620
  BCL11A-13278	+	AUACUUACUGUACUGCA	17	3′	15621
  BCL11A-13279	+	CACUGGAAACCCUGUUA	17	3′	15622
  BCL11A-13280	-	CUAUUUACAGCCAUAAC	17	3′	15623
  BCL11A-13281	+	CUACUUAUACAAUUCAC	17	3′	15624
  BCL11A-13282	+	AAUACUUACUGUACUGC	17	3′	15625
  BCL11A-13283	+	UACUUACUGUACUGCAG	17	3′	15626
  BCL11A-13284	+	UGUACUGCAGGGGAAUU	17	3′	15627
  BCL11A-13285	-	UGGGUAGCAGUGGCUUU	17	3′	15628
  BCL11A-13286	-	UGGCUUUAGGCUGUUUU	17	3′	15629
  BCL11A-13287	-	AACUAUUUACAGCCAUAACA	20	3′	15630
  BCL11A-13288	+	AAAAUACUUACUGUACUGCA	20	3′	15631
  BCL11A-13289	+	AUUCACUGGAAACCCUGUUA	20	3′	15632
  BCL11A-13290	-	AAACUAUUUACAGCCAUAAC	20	3′	15633
  BCL11A-13291	+	AAAUACUUACUGUACUGCAG	20	3′	15634
  BCL11A-13292	+	UACUGUACUGCAGGGGAAUU	20	3′	15635
  BCL11A-13293	-	UUAGGCUGUUUUUGGAUCUU	20	3′	15636
  BCL11A-13294	-	CAGUGGCUUUAGGCUGUUUU	20	3′	15637

• Table 21C provides exemplary targeting domains for removing (e.g., deleting) the enhancer region of the BCL11A gene selected according to the third tier parameters. The targeting domains bind within a region 5′ (51.5 to 51.7 kb downstream of TSS) or 3′ (65.1 to 65.3 kb 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 21C
  3rd Tier

  	DNA		Target Site		SEQ ID
  gRNA Name	Strand	Targeting Domain	Length		5′ or 3′	NO:
  BCL11A-13295	-	GAAUGUAGAGAGGCAGA	17	5′	15638
  BCL11A-13296	-	GGAAUGUAGAGAGGCAG	17	5′	15639
  BCL11A-13297	-	GUAUUUUCUUUCAUUGG	17	3′	15640
  BCL11A-13298	-	GUAAGUAUUUUCUUUCAUUG	20	3′	15641

• Table 21D provides exemplary targeting domains for removing (e.g., deleting) the enhancer region of the BCL11A gene selected according to the fourth tier parameters. The targeting domains bind within a region 5′ (51.5 to 51.7 kb downstream of TSS) or 3′ (65.1 to 65.3 kb 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 21D
  4th Tier

  			Target
  	DNA		Site		SEQ ID
  gRNA Name	Strand	Targeting Domain	Length		5′ or 3′	NO:
  BCL11A-13299	-	AAAAUAAUUAGAAUAAA	17	5′	15642
  BCL11A-13300	+	CACAUAAAAAUUUAAGA	17	5′	15643
  BCL11A-13301	+	ACAUAAAAAUUUAAGAC	17	5′	15644
  BCL11A-13302	-	UGUAAGGCUGGGCGCAG	17	5′	15645
  BCL11A-13303	-	AAUGUAGAGAGGCAGAG	17	5′	15646
  BCL11A-13304	-	AGAAUAAAAGGCUGUUU	17	5′	15647
  BCL11A-13305	-	AGUAAAAUAAUUAGAAUAAA	20	5′	15648
  BCL11A-13306	-	UUAAGAAAGCAGUGUAAGGC	20	5′	15649
  BCL11A-13307	-	CAGUGUAAGGCUGGGCGCAG	20	5′	15650
  BCL11A-13308	-	UUUGGAAUGUAGAGAGGCAG	20	5′	15651
  BCL11A-13309	-	UGGAAUGUAGAGAGGCAGAG	20	5′	15652
  BCL11A-13310	-	AGUAUUUUCUUUCAUUG	17	3′	15653
  BCL11A-13311	-	UAAGUAUUUUCUUUCAU	17	3′	15654
  BCL11A-13312	-	AAGUAUUUUCUUUCAUU	17	3′	15655
  BCL11A-13313	-	UAAGUAUUUUCUUUCAUUGG	20	3′	15656
  BCL11A-13314	-	CAGUAAGUAUUUUCUUUCAU	20	3′	15657
  BCL11A-13315	-	AGUAAGUAUUUUCUUUCAUU	20	3′	15658

• Table 21E provides targeting domains for removing (e.g., deleting) the enhancer region of the BCL11A 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, BCL11A-13271 or BCL11A-13264 can be combined with BCL11A-13276; or BCL11A-13262 or BCL11A-13282 can be combined with BCL11A-13290 or BCL11A-13280.

• 	TABLE 21E
  	Group A	Group B
  	BCL11A-13271, BCL11A-	BCL11A-13276
  	13264
  	Group C	Group D
  	BCL11A-13262, BCL11A-	BCL11A-13290, BCL11A-
  	13282	13280

• Table 22A provides exemplary targeting domains for removing (e.g., deleting) the enhancer region of the BCL11A gene selected according to the first tier parameters. The targeting domains bind within a region 5′ (51.5 to 51.7 kb downstream of TSS) or 3′ (65.1 to 65.3 kb 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 22A
  1st Tier

  			Target		SEQ
  	DNA		Site
  	5′	ID
  gRNA Name	Strand	Targeting Domain	Length	or 3′	NO:
  BCL11A-13316	−	GGGGCUGAUAUAACUUCU	18	5′	15659
  BCL11A-13317	−	GAGGGGCUGAUAUAACUUCU	20	5′	15660
  BCL11A-13318	−	GCAGAGGGGCUGAUAUAACUUCU	23	5′	15661
  BCL11A-13319	−	GGCAGAGGGGCUGAUAUAACUUCU	24	5′	15662
  BCL11A-13320	−	GCAAACUAUUUACAGCCAUAA	21	3′	15663
  BCL11A-13321	−	GAAGCAAACUAUUUACAGCCAUAA	24	3′	15664
  BCL11A-13322	−	GCCAUAACAGGGUUUCCA	18	3′	15665
  BCL11A-13323	−	GUGAAUUGUAUAAGUAGCA	19	3′	15666
  BCL11A-13324	−	GCAAAACUAGAAAGUUUUA	19	3′	15667
  BCL11A-13325	−	GCAGUGGCUUUAGGCUGUUU	20	3′	15668
  BCL11A-13326	−	GUAGCAGUGGCUUUAGGCUGUUU	23	3′	15669
  BCL11A-13327	−	GGUAGCAGUGGCUUUAGGCUGUUU	24	3′	15670

• Table 22B provides exemplary targeting domains for removing (e.g., deleting) the enhancer region of the BCL11A gene selected according to the second tier parameters. The targeting domains bind within a region 5′ (51.5 to 51.7 kb downstream of TSS) or 3′ (65.1 to 65.3 kb downstream of TSS), and have a high level of orthogonality. 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 22B
  2nd Tier

  			Target		SEQ
  	DNA		Site
  	5′	ID
  gRNA Name	Strand	Targeting Domain	Length	or 3′	NO:
  BCL11A-13328	+	UUUAUUCUAAUUAUUUUACUA	21	5′	15671
  BCL11A-13329	+	UUUUAUUCUAAUUAUUUUACUA	22	5′	15672
  BCL11A-13330	+	CUUUUAUUCUAAUUAUUUUACUA	23	5′	15673
  BCL11A-13331	+	CCUUUUAUUCUAAUUAUUUUACUA	24	5′	15674
  BCL11A-13332	+	UAUUUUACUAGUGAAUUA	18	5′	15675
  BCL11A-13333	+	UUAUUUUACUAGUGAAUUA	19	5′	15676
  BCL11A-13334	+	AUUAUUUUACUAGUGAAUUA	20	5′	15677
  BCL11A-13335	+	AAUUAUUUUACUAGUGAAUUA	21	5′	15678
  BCL11A-13336	+	UAAUUAUUUUACUAGUGAAUUA	22	5′	15679
  BCL11A-13337	+	CUAAUUAUUUUACUAGUGAAUUA	23	5′	15680
  BCL11A-13338	+	UCUAAUUAUUUUACUAGUGAAUUA	24	5′	15681
  BCL11A-13339	−	AUUCACUAGUAAAAUAAU	18	5′	15682
  BCL11A-13340	−	AAUUCACUAGUAAAAUAAU	19	5′	15683
  BCL11A-13341	−	UAAUUCACUAGUAAAAUAAU	20	5′	15684
  BCL11A-13342	−	AGGGGCUGAUAUAACUUCU	19	5′	15685
  BCL11A-13343	−	AGAGGGGCUGAUAUAACUUCU	21	5′	15686
  BCL11A-13344	−	CAGAGGGGCUGAUAUAACUUCU	22	5′	15687
  BCL11A-13345	−	UAGAAUAAAAGGCUGUUU	18	5′	15688
  BCL11A-13346	−	UUAGAAUAAAAGGCUGUUU	19	5′	15689
  BCL11A-13347	−	AUUAGAAUAAAAGGCUGUUU	20	5′	15690
  BCL11A-13348	−	AAUUAGAAUAAAAGGCUGUUU	21	5′	15691
  BCL11A-13349	−	UAAUUAGAAUAAAAGGCUGUUU	22	5′	15692
  BCL11A-13350	−	AUAAUUAGAAUAAAAGGCUGUUU	23	5′	15693
  BCL11A-13351	−	AAUAAUUAGAAUAAAAGGCUGUUU	24	5′	15694
  BCL11A-13352	+	AUACUUACUGUACUGCAG	18	3′	15695
  BCL11A-13353	+	AAUACUUACUGUACUGCAG	19	3′	15696
  BCL11A-13354	+	AAAUACUUACUGUACUGCAG	20	3′	15697
  BCL11A-13355	−	AACUAUUUACAGCCAUAA	18	3′	15698
  BCL11A-13356	−	AAACUAUUUACAGCCAUAA	19	3′	15699
  BCL11A-13357	−	CAAACUAUUUACAGCCAUAA	20	3′	15700
  BCL11A-13358	−	AGCAAACUAUUUACAGCCAUAA	22	3′	15701
  BCL11A-13359	−	AAGCAAACUAUUUACAGCCAUAA	23	3′	15702
  BCL11A-13360	−	AGCCAUAACAGGGUUUCCA	19	3′	15703
  BCL11A-13361	−	CAGCCAUAACAGGGUUUCCA	20	3′	15704
  BCL11A-13362	−	ACAGCCAUAACAGGGUUUCCA	21	3′	15705
  BCL11A-13363	−	UACAGCCAUAACAGGGUUUCCA	22	3′	15706
  BCL11A-13364	−	UUACAGCCAUAACAGGGUUUCCA	23	3′	15707
  BCL11A-13365	−	UUUACAGCCAUAACAGGGUUUCCA	24	3′	15708
  BCL11A-13366	−	UGAAUUGUAUAAGUAGCA	18	3′	15709
  BCL11A-13367	−	AGUGAAUUGUAUAAGUAGCA	20	3′	15710
  BCL11A-13368	−	CAGUGAAUUGUAUAAGUAGCA	21	3′	15711
  BCL11A-13369	−	CCAGUGAAUUGUAUAAGUAGCA	22	3′	15712
  BCL11A-13370	−	UCCAGUGAAUUGUAUAAGUAGCA	23	3′	15713
  BCL11A-13371	−	UUCCAGUGAAUUGUAUAAGUAGCA	24	3′	15714
  BCL11A-13372	−	CAAAACUAGAAAGUUUUA	18	3′	15715
  BCL11A-13373	−	AGCAAAACUAGAAAGUUUUA	20	3′	15716
  BCL11A-13374	−	AGUGGCUUUAGGCUGUUU	18	3′	15717
  BCL11A-13375	−	CAGUGGCUUUAGGCUGUUU	19	3′	15718
  BCL11A-13376	−	AGCAGUGGCUUUAGGCUGUUU	21	3′	15719
  BCL11A-13377	−	UAGCAGUGGCUUUAGGCUGUUU	22	3′	15720

• Table 22C provides exemplary targeting domains for removing (e.g., deleting) the enhancer region of the BCL11A gene selected according to the third tier parameters. The targeting domains bind within a region 5′ (51.5 to 51.7 kb downstream of TSS) or 3′ (65.1 to 65.3 kb 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 22C
  3rd Tier

  			Target		SEQ
  	DNA		Site
  	5′	ID
  gRNA Name	Strand	Targeting Domain	Length	or 3′	NO:
  BCL11A-13378	+	GAAAAUACUUACUGUACUGCAG	22	3′	15721
  BCL11A-13379	−	GUUAAGCAAAACUAGAAAGUUUUA	24	3′	15722

• Table 22D provides exemplary targeting domains for removing (e.g., deleting) the enhancer region of the BCL11A gene selected according to the second tier parameters. The targeting domains bind within a region 5′ (51.5 to 51.7 kb downstream of TSS) or 3′ (65.1 to 65.3 kb 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 22D
  4th Tier

  			Target		SEQ
  	DNA		Site
  	5′	ID
  gRNA Name	Strand	Targeting Domain	Length	or 3′	NO:
  BCL11A-13380	+	AUUCUAAUUAUUUUACUA	18	5′	15723
  BCL11A-13381	+	UAUUCUAAUUAUUUUACUA	19	5′	15724
  BCL11A-13382	+	UUAUUCUAAUUAUUUUACUA	20	5′	15725
  BCL11A-13383	−	AUAAUUCACUAGUAAAAUAAU	21	5′	15726
  BCL11A-13384	−	CAUAAUUCACUAGUAAAAUAAU	22	5′	15727
  BCL11A-13385	−	CCAUAAUUCACUAGUAAAAUAAU	23	5′	15728
  BCL11A-13386	−	UCCAUAAUUCACUAGUAAAAUAAU	24	5′	15729
  BCL11A-13387	+	AAAAUACUUACUGUACUGCAG	21	3′	15730
  BCL11A-13388	+	AGAAAAUACUUACUGUACUGCAG	23	3′	15731
  BCL11A-13389	+	AAGAAAAUACUUACUGUACUGCAG	24	3′	15732
  BCL11A-13390	−	AAGCAAAACUAGAAAGUUUUA	21	3′	15733
  BCL11A-13391	−	UAAGCAAAACUAGAAAGUUUUA	22	3′	15734
  BCL11A-13392	−	UUAAGCAAAACUAGAAAGUUUUA	23	3′	15735

• Table 22E provides exemplary targeting domains for removing (e.g., deleting) the enhancer region of the BCL11A gene selected according to the third tier parameters. The targeting domains bind within a region 5′ (51.5 to 51.7 kb downstream of TSS) or 3′ (65.1 to 65.3 kb 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 22E
  5th Tier

  			Target		SEQ
  	DNA		Site	5′	ID
  gRNA Name	Strand	Targeting Domain	Length	or 3′	NO:
  BCL11A-13393	+	AAAUUUAAGACGGGAAAA	18	5′	15736
  BCL11A-13394	+	AAAAUUUAAGACGGGAAAA	19	5′	15737
  BCL11A-13395	+	AAAAAUUUAAGACGGGAAAA	20	5′	15738
  BCL11A-13396	+	UAAAAAUUUAAGACGGGAAAA	21	5′	15739
  BCL11A-13397	+	AUAAAAAUUUAAGACGGGAAAA	22	5′	15740
  BCL11A-13398	+	CAUAAAAAUUUAAGACGGGAAAA	23	5′	15741
  BCL11A-13399	+	ACAUAAAAAUUUAAGACGGGAAAA	24	5′	15742
  BCL11A-13400	+	UCACAUAAAAAUUUAAGA	18	5′	15743
  BCL11A-13401	+	CUCACAUAAAAAUUUAAGA	19	5′	15744
  BCL11A-13402	+	UCUCACAUAAAAAUUUAAGA	20	5′	15745
  BCL11A-13403	+	AUCUCACAUAAAAAUUUAAGA	21	5′	15746
  BCL11A-13404	+	CAUCUCACAUAAAAAUUUAAGA	22	5′	15747
  BCL11A-13405	+	UCAUCUCACAUAAAAAUUUAAGA	23	5′	15748
  BCL11A-13406	+	CUCAUCUCACAUAAAAAUUUAAGA	24	5′	15749
  BCL11A-13407	+	AAUUUAAGACGGGAAAAC	18	5′	15750
  BCL11A-13408	+	AAAUUUAAGACGGGAAAAC	19	5′	15751
  BCL11A-13409	+	AAAAUUUAAGACGGGAAAAC	20	5′	15752
  BCL11A-13410	+	AAAAAUUUAAGACGGGAAAAC	21	5′	15753
  BCL11A-13411	+	UAAAAAUUUAAGACGGGAAAAC	22	5′	15754
  BCL11A-13412	+	AUAAAAAUUUAAGACGGGAAAAC	23	5′	15755
  BCL11A-13413	+	CAUAAAAAUUUAAGACGGGAAAAC	24	5′	15756
  BCL11A-13414	+	CACAUAAAAAUUUAAGAC	18	5′	15757
  BCL11A-13415	+	UCACAUAAAAAUUUAAGAC	19	5′	15758
  BCL11A-13416	+	CUCACAUAAAAAUUUAAGAC	20	5′	15759
  BCL11A-13417	+	UCUCACAUAAAAAUUUAAGAC	21	5′	15760
  BCL11A-13418	+	AUCUCACAUAAAAAUUUAAGAC	22	5′	15761
  BCL11A-13419	+	CAUCUCACAUAAAAAUUUAAGAC	23	5′	15762
  BCL11A-13420	+	UCAUCUCACAUAAAAAUUUAAGAC	24	5′	15763
  BCL11A-13421	+	CUCACAUAAAAAUUUAAG	18	5′	15764
  BCL11A-13422	+	UCUCACAUAAAAAUUUAAG	19	5′	15765
  BCL11A-13423	+	AUCUCACAUAAAAAUUUAAG	20	5′	15766
  BCL11A-13424	+	CAUCUCACAUAAAAAUUUAAG	21	5′	15767
  BCL11A-13425	+	UCAUCUCACAUAAAAAUUUAAG	22	5′	15768
  BCL11A-13426	+	CUCAUCUCACAUAAAAAUUUAAG	23	5′	15769
  BCL11A-13427	+	GCUCAUCUCACAUAAAAAUUUAAG	24	5′	15770
  BCL11A-13428	+	CAACUUGUGUUGCACUAG	18	5′	15771
  BCL11A-13429	+	ACAACUUGUGUUGCACUAG	19	5′	15772
  BCL11A-13430	+	CACAACUUGUGUUGCACUAG	20	5′	15773
  BCL11A-13431	+	ACACAACUUGUGUUGCACUAG	21	5′	15774
  BCL11A-13432	+	UACACAACUUGUGUUGCACUAG	22	5′	15775
  BCL11A-13433	+	CUACACAACUUGUGUUGCACUAG	23	5′	15776
  BCL11A-13434	+	UCUACACAACUUGUGUUGCACUAG	24	5′	15777
  BCL11A-13435	+	AACAGGAAGAUGCAUUCU	18	5′	15778
  BCL11A-13436	+	AAACAGGAAGAUGCAUUCU	19	5′	15779
  BCL11A-13437	+	AAAACAGGAAGAUGCAUUCU	20	5′	15780
  BCL11A-13438	+	GAAAACAGGAAGAUGCAUUCU	21	5′	15781
  BCL11A-13439	+	GGAAAACAGGAAGAUGCAUUCU	22	5′	15782
  BCL11A-13440	+	GGGAAAACAGGAAGAUGCAUUCU	23	5′	15783
  BCL11A-13441	+	CGGGAAAACAGGAAGAUGCAUUCU	24	5′	15784
  BCL11A-13442	+	UUAUUUUACUAGUGAAUU	18	5′	15785
  BCL11A-13443	+	AUUAUUUUACUAGUGAAUU	19	5′	15786
  BCL11A-13444	+	AAUUAUUUUACUAGUGAAUU	20	5′	15787
  BCL11A-13445	+	UAAUUAUUUUACUAGUGAAUU	21	5′	15788
  BCL11A-13446	+	CUAAUUAUUUUACUAGUGAAUU	22	5′	15789
  BCL11A-13447	+	UCUAAUUAUUUUACUAGUGAAUU	23	5′	15790
  BCL11A-13448	+	UUCUAAUUAUUUUACUAGUGAAUU	24	5′	15791
  BCL11A-13449	+	AAAACAGGAAGAUGCAUU	18	5′	15792
  BCL11A-13450	+	GAAAACAGGAAGAUGCAUU	19	5′	15793
  BCL11A-13451	+	GGAAAACAGGAAGAUGCAUU	20	5′	15794
  BCL11A-13452	+	GGGAAAACAGGAAGAUGCAUU	21	5′	15795
  BCL11A-13453	+	CGGGAAAACAGGAAGAUGCAUU	22	5′	15796
  BCL11A-13454	+	ACGGGAAAACAGGAAGAUGCAUU	23	5′	15797
  BCL11A-13455	+	GACGGGAAAACAGGAAGAUGCAUU	24	5′	15798
  BCL11A-13456	−	UUGGAAUGUAGAGAGGCA	18	5′	15799
  BCL11A-13457	−	UUUGGAAUGUAGAGAGGCA	19	5′	15800
  BCL11A-13458	−	UUUUGGAAUGUAGAGAGGCA	20	5′	15801
  BCL11A-13459	−	GUUUUGGAAUGUAGAGAGGCA	21	5′	15802
  BCL11A-13460	−	UGUUUUGGAAUGUAGAGAGGCA	22	5′	15803
  BCL11A-13461	−	CUGUUUUGGAAUGUAGAGAGGCA	23	5′	15804
  BCL11A-13462	−	GCUGUUUUGGAAUGUAGAGAGGCA	24	5′	15805
  BCL11A-13463	−	CAACACAAGUUGUGUAGA	18	5′	15806
  BCL11A-13464	−	GCAACACAAGUUGUGUAGA	19	5′	15807
  BCL11A-13465	−	UGCAACACAAGUUGUGUAGA	20	5′	15808
  BCL11A-13466	−	GUGCAACACAAGUUGUGUAGA	21	5′	15809
  BCL11A-13467	−	AGUGCAACACAAGUUGUGUAGA	22	5′	15810
  BCL11A-13468	−	UAGUGCAACACAAGUUGUGUAGA	23	5′	15811
  BCL11A-13469	−	CUAGUGCAACACAAGUUGUGUAGA	24	5′	15812
  BCL11A-13470	−	AGGCUGUUUUGGAAUGUA	18	5′	15813
  BCL11A-13471	−	AAGGCUGUUUUGGAAUGUA	19	5′	15814
  BCL11A-13472	−	AAAGGCUGUUUUGGAAUGUA	20	5′	15815
  BCL11A-13473	−	AAAAGGCUGUUUUGGAAUGUA	21	5′	15816
  BCL11A-13474	−	UAAAAGGCUGUUUUGGAAUGUA	22	5′	15817
  BCL11A-13475	−	AUAAAAGGCUGUUUUGGAAUGUA	23	5′	15818
  BCL11A-13476	−	AAUAAAAGGCUGUUUUGGAAUGUA	24	5′	15819
  BCL11A-13477	−	UGGAAUGUAGAGAGGCAG	18	5′	15820
  BCL11A-13478	−	UUGGAAUGUAGAGAGGCAG	19	5′	15821
  BCL11A-13479	−	UUUGGAAUGUAGAGAGGCAG	20	5′	15822
  BCL11A-13480	−	UUUUGGAAUGUAGAGAGGCAG	21	5′	15823
  BCL11A-13481	−	GUUUUGGAAUGUAGAGAGGCAG	22	5′	15824
  BCL11A-13482	−	UGUUUUGGAAUGUAGAGAGGCAG	23	5′	15825
  BCL11A-13483	−	CUGUUUUGGAAUGUAGAGAGGCAG	24	5′	15826
  BCL11A-13484	−	CUUAAAUUUUUAUGUGAG	18	5′	15827
  BCL11A-13485	−	UCUUAAAUUUUUAUGUGAG	19	5′	15828
  BCL11A-13486	−	GUCUUAAAUUUUUAUGUGAG	20	5′	15829
  BCL11A-13487	−	CGUCUUAAAUUUUUAUGUGAG	21	5′	15830
  BCL11A-13488	−	CCGUCUUAAAUUUUUAUGUGAG	22	5′	15831
  BCL11A-13489	−	CCCGUCUUAAAUUUUUAUGUGAG	23	5′	15832
  BCL11A-13490	−	UCCCGUCUUAAAUUUUUAUGUGAG	24	5′	15833
  BCL11A-13491	−	UAAGAAAGCAGUGUAAGG	18	5′	15834
  BCL11A-13492	−	UUAAGAAAGCAGUGUAAGG	19	5′	15835
  BCL11A-13493	−	AUUAAGAAAGCAGUGUAAGG	20	5′	15836
  BCL11A-13494	−	AAUUAAGAAAGCAGUGUAAGG	21	5′	15837
  BCL11A-13495	−	UAAUUAAGAAAGCAGUGUAAGG	22	5′	15838
  BCL11A-13496	−	GUAAUUAAGAAAGCAGUGUAAGG	23	5′	15839
  BCL11A-13497	−	UGUAAUUAAGAAAGCAGUGUAAGG	24	5′	15840
  BCL11A-13498	−	UUUUGGAAUGUAGAGAGG	18	5′	15841
  BCL11A-13499	−	GUUUUGGAAUGUAGAGAGG	19	5′	15842
  BCL11A-13500	−	UGUUUUGGAAUGUAGAGAGG	20	5′	15843
  BCL11A-13501	−	CUGUUUUGGAAUGUAGAGAGG	21	5′	15844
  BCL11A-13502	−	GCUGUUUUGGAAUGUAGAGAGG	22	5′	15845
  BCL11A-13503	−	GGCUGUUUUGGAAUGUAGAGAGG	23	5′	15846
  BCL11A-13504	−	AGGCUGUUUUGGAAUGUAGAGAGG	24	5′	15847
  BCL11A-13505	−	AAAGGCUGUUUUGGAAUG	18	5′	15848
  BCL11A-13506	−	AAAAGGCUGUUUUGGAAUG	19	5′	15849
  BCL11A-13507	−	UAAAAGGCUGUUUUGGAAUG	20	5′	15850
  BCL11A-13508	−	AUAAAAGGCUGUUUUGGAAUG	21	5′	15851
  BCL11A-13509	−	AAUAAAAGGCUGUUUUGGAAUG	22	5′	15852
  BCL11A-13510	−	GAAUAAAAGGCUGUUUUGGAAUG	23	5′	15853
  BCL11A-13511	−	AGAAUAAAAGGCUGUUUUGGAAUG	24	5′	15854
  BCL11A-13512	−	AGUGCAACACAAGUUGUG	18	5′	15855
  BCL11A-13513	−	UAGUGCAACACAAGUUGUG	19	5′	15856
  BCL11A-13514	−	CUAGUGCAACACAAGUUGUG	20	5′	15857
  BCL11A-13515	−	CCUAGUGCAACACAAGUUGUG	21	5′	15858
  BCL11A-13516	−	ACCUAGUGCAACACAAGUUGUG	22	5′	15859
  BCL11A-13517	−	CACCUAGUGCAACACAAGUUGUG	23	5′	15860
  BCL11A-13518	−	UCACCUAGUGCAACACAAGUUGUG	24	5′	15861
  BCL11A-13519	−	CCCGUCUUAAAUUUUUAU	18	5′	15862
  BCL11A-13520	−	UCCCGUCUUAAAUUUUUAU	19	5′	15863
  BCL11A-13521	−	UUCCCGUCUUAAAUUUUUAU	20	5′	15864
  BCL11A-13522	−	UUUCCCGUCUUAAAUUUUUAU	21	5′	15865
  BCL11A-13523	−	UUUUCCCGUCUUAAAUUUUUAU	22	5′	15866
  BCL11A-13524	−	GUUUUCCCGUCUUAAAUUUUUAU	23	5′	15867
  BCL11A-13525	−	UGUUUUCCCGUCUUAAAUUUUUAU	24	5′	15868
  BCL11A-13526	−	GAGCACACUGCUGUAAUU	18	5′	15869
  BCL11A-13527	−	UGAGCACACUGCUGUAAUU	19	5′	15870
  BCL11A-13528	−	AUGAGCACACUGCUGUAAUU	20	5′	15871
  BCL11A-13529	−	GAUGAGCACACUGCUGUAAUU	21	5′	15872
  BCL11A-13530	−	AGAUGAGCACACUGCUGUAAUU	22	5′	15873
  BCL11A-13531	−	GAGAUGAGCACACUGCUGUAAUU	23	5′	15874
  BCL11A-13532	−	UGAGAUGAGCACACUGCUGUAAUU	24	5′	15875
  BCL11A-13533	−	UUAGAAUAAAAGGCUGUU	18	5′	15876
  BCL11A-13534	−	AUUAGAAUAAAAGGCUGUU	19	5′	15877
  BCL11A-13535	−	AAUUAGAAUAAAAGGCUGUU	20	5′	15878
  BCL11A-13536	−	UAAUUAGAAUAAAAGGCUGUU	21	5′	15879
  BCL11A-13537	−	AUAAUUAGAAUAAAAGGCUGUU	22	5′	15880
  BCL11A-13538	−	AAUAAUUAGAAUAAAAGGCUGUU	23	5′	15881
  BCL11A-13539	−	AAAUAAUUAGAAUAAAAGGCUGUU	24	5′	15882
  BCL11A-13540	+	UUUCAUUUUUUGCUGACA	18	3′	15883
  BCL11A-13541	+	GUUUCAUUUUUUGCUGACA	19	3′	15884
  BCL11A-13542	+	UGUUUCAUUUUUUGCUGACA	20	3′	15885
  BCL11A-13543	+	UUGUUUCAUUUUUUGCUGACA	21	3′	15886
  BCL11A-13544	+	UUUGUUUCAUUUUUUGCUGACA	22	3′	15887
  BCL11A-13545	+	UUUUGUUUCAUUUUUUGCUGACA	23	3′	15888
  BCL11A-13546	+	UUUUUGUUUCAUUUUUUGCUGACA	24	3′	15889
  BCL11A-13547	+	AAUAGUUUGCUUCCCCCA	18	3′	15890
  BCL11A-13548	+	AAAUAGUUUGCUUCCCCCA	19	3′	15891
  BCL11A-13549	+	UAAAUAGUUUGCUUCCCCCA	20	3′	15892
  BCL11A-13550	+	GUAAAUAGUUUGCUUCCCCCA	21	3′	15893
  BCL11A-13551	+	UGUAAAUAGUUUGCUUCCCCCA	22	3′	15894
  BCL11A-13552	+	CUGUAAAUAGUUUGCUUCCCCCA	23	3′	15895
  BCL11A-13553	+	GCUGUAAAUAGUUUGCUUCCCCCA	24	3′	15896
  BCL11A-13554	+	AAUACUUACUGUACUGCA	18	3′	15897
  BCL11A-13555	+	AAAUACUUACUGUACUGCA	19	3′	15898
  BCL11A-13556	+	AAAAUACUUACUGUACUGCA	20	3′	15899
  BCL11A-13557	+	GAAAAUACUUACUGUACUGCA	21	3′	15900
  BCL11A-13558	+	AGAAAAUACUUACUGUACUGCA	22	3′	15901
  BCL11A-13559	+	AAGAAAAUACUUACUGUACUGCA	23	3′	15902
  BCL11A-13560	+	AAAGAAAAUACUUACUGUACUGCA	24	3′	15903
  BCL11A-13561	+	UGCUACUUAUACAAUUCA	18	3′	15904
  BCL11A-13562	+	GUGCUACUUAUACAAUUCA	19	3′	15905
  BCL11A-13563	+	AGUGCUACUUAUACAAUUCA	20	3′	15906
  BCL11A-13564	+	CAGUGCUACUUAUACAAUUCA	21	3′	15907
  BCL11A-13565	+	UCAGUGCUACUUAUACAAUUCA	22	3′	15908
  BCL11A-13566	+	CUCAGUGCUACUUAUACAAUUCA	23	3′	15909
  BCL11A-13567	+	ACUCAGUGCUACUUAUACAAUUCA	24	3′	15910
  BCL11A-13568	+	GUUUGCUUCCCCCAAUGA	18	3′	15911
  BCL11A-13569	+	AGUUUGCUUCCCCCAAUGA	19	3′	15912
  BCL11A-13570	+	UAGUUUGCUUCCCCCAAUGA	20	3′	15913
  BCL11A-13571	+	AUAGUUUGCUUCCCCCAAUGA	21	3′	15914
  BCL11A-13572	+	AAUAGUUUGCUUCCCCCAAUGA	22	3′	15915
  BCL11A-13573	+	AAAUAGUUUGCUUCCCCCAAUGA	23	3′	15916
  BCL11A-13574	+	UAAAUAGUUUGCUUCCCCCAAUGA	24	3′	15917
  BCL11A-13575	+	UUUCUAGUUUUGCUUAAC	18	3′	15918
  BCL11A-13576	+	CUUUCUAGUUUUGCUUAAC	19	3′	15919
  BCL11A-13577	+	ACUUUCUAGUUUUGCUUAAC	20	3′	15920
  BCL11A-13578	+	AACUUUCUAGUUUUGCUUAAC	21	3′	15921
  BCL11A-13579	+	AAACUUUCUAGUUUUGCUUAAC	22	3′	15922
  BCL11A-13580	+	AAAACUUUCUAGUUUUGCUUAAC	23	3′	15923
  BCL11A-13581	+	UAAAACUUUCUAGUUUUGCUUAAC	24	3′	15924
  BCL11A-13582	+	GCUACUUAUACAAUUCAC	18	3′	15925
  BCL11A-13583	+	UGCUACUUAUACAAUUCAC	19	3′	15926
  BCL11A-13584	+	GUGCUACUUAUACAAUUCAC	20	3′	15927
  BCL11A-13585	+	AGUGCUACUUAUACAAUUCAC	21	3′	15928
  BCL11A-13586	+	CAGUGCUACUUAUACAAUUCAC	22	3′	15929
  BCL11A-13587	+	UCAGUGCUACUUAUACAAUUCAC	23	3′	15930
  BCL11A-13588	+	CUCAGUGCUACUUAUACAAUUCAC	24	3′	15931
  BCL11A-13589	+	AAAUACUUACUGUACUGC	18	3′	15932
  BCL11A-13590	+	AAAAUACUUACUGUACUGC	19	3′	15933
  BCL11A-13591	+	GAAAAUACUUACUGUACUGC	20	3′	15934
  BCL11A-13592	+	AGAAAAUACUUACUGUACUGC	21	3′	15935
  BCL11A-13593	+	AAGAAAAUACUUACUGUACUGC	22	3′	15936
  BCL11A-13594	+	AAAGAAAAUACUUACUGUACUGC	23	3′	15937
  BCL11A-13595	+	GAAAGAAAAUACUUACUGUACUGC	24	3′	15938
  BCL11A-13596	+	AAAAUACUUACUGUACUG	18	3′	15939
  BCL11A-13597	+	GAAAAUACUUACUGUACUG	19	3′	15940
  BCL11A-13598	+	AGAAAAUACUUACUGUACUG	20	3′	15941
  BCL11A-13599	+	AAGAAAAUACUUACUGUACUG	21	3′	15942
  BCL11A-13600	+	AAAGAAAAUACUUACUGUACUG	22	3′	15943
  BCL11A-13601	+	GAAAGAAAAUACUUACUGUACUG	23	3′	15944
  BCL11A-13602	+	UGAAAGAAAAUACUUACUGUACUG	24	3′	15945
  BCL11A-13603	−	GUUCUGUGUCAGCAAAAA	18	3′	15946
  BCL11A-13604	−	AGUUCUGUGUCAGCAAAAA	19	3′	15947
  BCL11A-13605	−	GAGUUCUGUGUCAGCAAAAA	20	3′	15948
  BCL11A-13606	−	UGAGUUCUGUGUCAGCAAAAA	21	3′	15949
  BCL11A-13607	−	CUGAGUUCUGUGUCAGCAAAAA	22	3′	15950
  BCL11A-13608	−	ACUGAGUUCUGUGUCAGCAAAAA	23	3′	15951
  BCL11A-13609	−	CACUGAGUUCUGUGUCAGCAAAAA	24	3′	15952
  BCL11A-13610	−	AGUAAGUAUUUUCUUUCA	18	3′	15953
  BCL11A-13611	−	CAGUAAGUAUUUUCUUUCA	19	3′	15954
  BCL11A-13612	−	ACAGUAAGUAUUUUCUUUCA	20	3′	15955
  BCL11A-13613	−	UACAGUAAGUAUUUUCUUUCA	21	3′	15956
  BCL11A-13614	−	GUACAGUAAGUAUUUUCUUUCA	22	3′	15957
  BCL11A-13615	−	AGUACAGUAAGUAUUUUCUUUCA	23	3′	15958
  BCL11A-13616	−	CAGUACAGUAAGUAUUUUCUUUCA	24	3′	15959
  BCL11A-13617	−	UUUCAUGUUAAGCAAAAC	18	3′	15960
  BCL11A-13618	−	UUUUCAUGUUAAGCAAAAC	19	3′	15961
  BCL11A-13619	−	AUUUUCAUGUUAAGCAAAAC	20	3′	15962
  BCL11A-13620	−	UAUUUUCAUGUUAAGCAAAAC	21	3′	15963
  BCL11A-13621	−	UUAUUUUCAUGUUAAGCAAAAC	22	3′	15964
  BCL11A-13622	−	AUUAUUUUCAUGUUAAGCAAAAC	23	3′	15965
  BCL11A-13623	−	UAUUAUUUUCAUGUUAAGCAAAAC	24	3′	15966
  BCL11A-13624	−	AGUAUUUUCUUUCAUUGG	18	3′	15967
  BCL11A-13625	−	AAGUAUUUUCUUUCAUUGG	19	3′	15968
  BCL11A-13626	−	UAAGUAUUUUCUUUCAUUGG	20	3′	15969
  BCL11A-13627	−	GUAAGUAUUUUCUUUCAUUGG	21	3′	15970
  BCL11A-13628	−	AGUAAGUAUUUUCUUUCAUUGG	22	3′	15971
  BCL11A-13629	−	CAGUAAGUAUUUUCUUUCAUUGG	23	3′	15972
  BCL11A-13630	−	ACAGUAAGUAUUUUCUUUCAUUGG	24	3′	15973
  BCL11A-13631	−	AAGUAUUUUCUUUCAUUG	18	3′	15974
  BCL11A-13632	−	UAAGUAUUUUCUUUCAUUG	19	3′	15975
  BCL11A-13633	−	GUAAGUAUUUUCUUUCAUUG	20	3′	15976
  BCL11A-13634	−	AGUAAGUAUUUUCUUUCAUUG	21	3′	15977
  BCL11A-13635	−	CAGUAAGUAUUUUCUUUCAUUG	22	3′	15978
  BCL11A-13636	−	ACAGUAAGUAUUUUCUUUCAUUG	23	3′	15979
  BCL11A-13637	−	UACAGUAAGUAUUUUCUUUCAUUG	24	3′	15980
  BCL11A-13638	−	GUAAGUAUUUUCUUUCAU	18	3′	15981
  BCL11A-13639	−	AGUAAGUAUUUUCUUUCAU	19	3′	15982
  BCL11A-13640	−	CAGUAAGUAUUUUCUUUCAU	20	3′	15983
  BCL11A-13641	−	ACAGUAAGUAUUUUCUUUCAU	21	3′	15984
  BCL11A-13642	−	UACAGUAAGUAUUUUCUUUCAU	22	3′	15985
  BCL11A-13643	−	GUACAGUAAGUAUUUUCUUUCAU	23	3′	15986
  BCL11A-13644	−	AGUACAGUAAGUAUUUUCUUUCAU	24	3′	15987
  BCL11A-13645	−	UUGGCUAUUGAUACUGAU	18	3′	15988
  BCL11A-13646	−	UUUGGCUAUUGAUACUGAU	19	3′	15989
  BCL11A-13647	−	CUUUGGCUAUUGAUACUGAU	20	3′	15990
  BCL11A-13648	−	UCUUUGGCUAUUGAUACUGAU	21	3′	15991
  BCL11A-13649	−	AUCUUUGGCUAUUGAUACUGAU	22	3′	15992
  BCL11A-13650	−	GAUCUUUGGCUAUUGAUACUGAU	23	3′	15993
  BCL11A-13651	−	GGAUCUUUGGCUAUUGAUACUGAU	24	3′	15994
  BCL11A-13652	−	UAAGUAUUUUCUUUCAUU	18	3′	15995
  BCL11A-13653	−	GUAAGUAUUUUCUUUCAUU	19	3′	15996
  BCL11A-13654	−	AGUAAGUAUUUUCUUUCAUU	20	3′	15997
  BCL11A-13655	−	CAGUAAGUAUUUUCUUUCAUU	21	3′	15998
  BCL11A-13656	−	ACAGUAAGUAUUUUCUUUCAUU	22	3′	15999
  BCL11A-13657	−	UACAGUAAGUAUUUUCUUUCAUU	23	3′	16000
  BCL11A-13658	−	GUACAGUAAGUAUUUUCUUUCAUU	24	3′	16001

• Table 23A provides exemplary targeting domains for removing (e.g., deleting) the enhancer region of the BCL11A gene selected according to the first tier parameters. The targeting domains bind within a region 5′ (51.5 to 51.7 kb downstream of TSS) or 3′ (65.1 to 65.3 kb 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 23A
  1st Tier

  			Target		SEQ
  	DNA		Site
  	5′	ID
  gRNA Name	Strand	Targeting Domain	Length	or 3′	NO:
  BCL11A-13659	−	GGAUCUUUGGCUAUUGA	17	3′	16002

• Table 23B provides exemplary targeting domains for removing (e.g., deleting) the enhancer region of the BCL11A gene selected according to the second tier parameters. The targeting domains bind within a region 5′ (51.5 to 51.7 kb downstream of TSS) or 3′ (65.1 to 65.3 kb 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 23B
  2nd Tier

  			Target		SEQ
  	DNA		Site
  	5′	ID
  gRNA Name	Strand	Targeting Domain	Length	or 3′	NO:
  BCL11A-13660	+	UCGGUAAAACUUUCUAG		17	3′	16003
  BCL11A-13661	−	UUUGGAUCUUUGGCUAUUGA	20	3′	16004
  BCL11A-13662	+	CCCUGUUAUGGCUGUAAAUA		20	3′	16005
  BCL11A-13663	+	AAUUCGGUAAAACUUUCUAG		20	3′	16006

• Table 23C provides exemplary targeting domains for removing (e.g., deleting) the enhancer region of the BCL11A gene selected according to the fourth tier parameters. The targeting domains bind within a region 5′ (51.5 to 51.7 kb downstream of TSS) or 3′ (65.1 to 65.3 kb 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 23C
  4th Tier

  			Target		SEQ
  	DNA		Site
  	5′	ID
  gRNA Name	Strand	Targeting Domain	Length	or 3′	NO:
  BCL11A-13664	+	CACUGCGCCCAGCCUUA		17	5′	16007
  BCL11A-13665	+	AGCCACUGCGCCCAGCCUUA		20	5′	16008
  BCL11A-13666	+	UGUUAUGGCUGUAAAUA		17	3′	16009

• Table 24A provides exemplary targeting domains for correcting a mutation (e.g., E6V) in the HBB gene selected according to the first tier parameters. The targeting domains bind within 200 bp to a mutation (e.g., E6V) and have a high level of orthogonality. 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 24A
  1st Tier

  			Target	SEQ
  gRNA	DNA		Site	ID
  Name	Strand	Targeting Domain	Length	NO:
  HBB-19	+	GUUCACCUUGCCCCACA	17	16010
  HBB-5	+	AGGAGUCAGGUGCACCA	17	16011
  HBB-40	−	UACUGCCCUGUGGGGCA	17	16012
  HBB-70	−	GCUGGGCAUAAAAGUCA	17	16013
  HBB-71	−	GUUACAAGACAGGUUUA	17	16014
  HBB-72	−	AGGAGACCAAUAGAAAC	17	16015
  HBB-37	+	CGUUCACCUUGCCCCAC	17	16016
  HBB-3	+	ACGGCAGACUUCUCCAC	17	16017
  HBB-41	−	UAUCAAGGUUACAAGAC	17	16018
  HBB-73	+	ACUUUUAUGCCCAGCCC	17	16019
  HBB-74	−	GGCUGGGCAUAAAAGUC	17	16020
  HBB-4	+	ACUUCUCCACAGGAGUC	17	16021
  HBB-75	−	AAUAGAAACUGGGCAUG	17	16022
  HBB-38	−	CUGCCGUUACUGCCCUG	17	16023
  HBB-13	−	GGAUGAAGUUGGUGGUG	17	16024
  HBB-12	−	GCCGUUACUGCCCUGUG	17	16025
  HBB-76	+	ACAUGCCCAGUUUCUAU	17	16026
  HBB-77	−	GGAGACCAAUAGAAACU	17	16027
  HBB-15	−	GUGAACGUGGAUGAAGU	17	16028
  HBB-47	−	UGCCGUUACUGCCCUGU	17	16029
  HBB-39	+	CUUGCCCCACAGGGCAGUAA	20	16030
  HBB-30	+	CACGUUCACCUUGCCCCACA	20	16031
  HBB-7	+	CACAGGAGUCAGGUGCACCA	20	16032
  HBB-78	−	AGCAGGGAGGGCAGGAGCCA	20	16033
  HBB-36	−	CGUUACUGCCCUGUGGGGCA	20	16034
  HBB-79	−	AGGGCUGGGCAUAAAAGUCA	20	16035
  HBB-22	+	AAGCAAAUGUAAGCAAUAGA	20	16036
  HBB-80	−	AAGGUUACAAGACAGGUUUA	20	16037
  HBB-81	−	UUAAGGAGACCAAUAGAAAC	20	16038
  HBB-2	+	GUAACGGCAGACUUCUCCAC	20	16039
  HBB-49	−	UGGUAUCAAGGUUACAAGAC	20	16040
  HBB-82	+	CUGACUUUUAUGCCCAGCCC	20	16041
  HBB-43	−	UGAAGUUGGUGGUGAGGCCC	20	16042
  HBB-83	−	GAGCAGGGAGGGCAGGAGCC	20	16043
  HBB-84	−	CAGGGCUGGGCAUAAAAGUC	20	16044
  HBB-8	+	CAGACUUCUCCACAGGAGUC	20	16045
  HBB-16	−	GUGAACGUGGAUGAAGUUGG	20	16046
  HBB-85	−	ACCAAUAGAAACUGGGCAUG	20	16047
  HBB-27	−	AGUCUGCCGUUACUGCCCUG	20	16048
  HBB-35	−	CGUGGAUGAAGUUGGUGGUG	20	16049
  HBB-42	−	UCUGCCGUUACUGCCCUGUG	20	16050
  HBB-86	−	UAAGGAGACCAAUAGAAACU	20	16051
  HBB-9	−	GAAGUUGGUGGUGAGGCCCU	20	16052
  HBB-87	−	GGAGGGCAGGAGCCAGGGCU	20	16053
  HBB-23	−	AAGGUGAACGUGGAUGAAGU	20	16054
  HBB-14	−	GUCUGCCGUUACUGCCCUGU	20	16055

• Table 24B provides exemplary targeting domains for correcting a mutation (e.g., E6V) in the HBB gene selected according to the second tier parameters. The targeting domains bind within 200 bp to a mutation (e.g., E6V) and start with 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).

• TABLE 24B
  2nd Tier

  			Target	SEQ
  gRNA	DNA		Site	ID
  Name	Strand	Targeting Domain	Length	NO:
  HBB-11	+	GCCCCACAGGGCAGUAA		17	16056
  HBB-18	−	GUGGUGAGGCCCUGGGC	17	16057
  HBB-17	−	GUGGGGCAAGGUGAACG	17	16058
  HBB-1	−	GGUGCACCUGACUCCUG	17	16059
  HBB-20	−	GUUGGUGGUGAGGCCCU	17	16060
  HBB-88	−	GGGCAGGAGCCAGGGCU	17	16061
  HBB-10	−	GCAACCUCAAACAGACACCA	20	16062
  HBB-89	−	GGGAGGGCAGGAGCCAGGGC	20	16063

• Table 24C provides exemplary targeting domains for correcting a mutation (e.g., E6V) in the HBB gene selected according to the third tier parameters. The targeting domains bind within 200 bp to a mutation (e.g., E6V). 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 24C
  3rd Tier

  			Target	SEQ
  gRNA	DNA		Site	ID
  Name	Strand	Targeting Domain	Length	NO:
  HBB-25	−	ACCUCAAACAGACACCA	17	16064
  HBB-45	+	UGAUACCAACCUGCCCA		17	16065
  HBB-90	−	AGGGAGGGCAGGAGCCA	17	16066
  HBB-48	−	UGGGCAGGUUGGUAUCA	17	16067
  HBB-29	+	CAAAUGUAAGCAAUAGA		17	16068
  HBB-28	−	AGUUGGUGGUGAGGCCC	17	16069
  HBB-51	+	UUGAUACCAACCUGCCC		17	16070
  HBB-91	−	CAGGGAGGGCAGGAGCC	17	16071
  HBB-92	−	AGGGCAGGAGCCAGGGC	17	16072
  HBB-21	−	AACGUGGAUGAAGUUGG	17	16073
  HBB-24	+	ACCAUGGUGUCUGUUUG		17	16074
  HBB-44	−	UGAGGCCCUGGGCAGGU	17	16075
  HBB-34	+	CCUUGAUACCAACCUGCCCA		20	16076
  HBB-32	−	CCCUGGGCAGGUUGGUAUCA	20	16077
  HBB-31	+	CCACGUUCACCUUGCCCCAC		20	16078
  HBB-26	+	ACCUUGAUACCAACCUGCCC		20	16079
  HBB-52	−	UUGGUGGUGAGGCCCUGGGC	20	16080
  HBB-33	−	CCUGUGGGGCAAGGUGAACG	20	16081
  HBB-6	−	CAUGGUGCACCUGACUCCUG	20	16082
  HBB-46	+	UGCACCAUGGUGUCUGUUUG		20	16083
  HBB-50	−	UGGUGAGGCCCUGGGCAGGU	20	16084

• Table 24D provides targeting domains for correcting a mutation (e.g., E6V) in the HBB 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 0-50 bp. Exemplary nickase pairs include a targeting domain from Group A and a second targeting domain from Group B in Table 24D (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 Table 24D (for S. pyogenes). For example, HBB-9 or HBB-20 can be combined with HBB-11 or HBB-39.

• 	TABLE 24D
  	Group A	Group B
  	HBB-9, HBB-20	HBB-11, HBB-39

• Table 25A provides exemplary targeting domains for correcting a mutation (e.g., E6V) in the HBB gene selected according to the first tier parameters. The targeting domains bind within 200 bp to a mutation (e.g., E6V), and have a high level of orthogonality. The PAM is NNGRRT. 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 25A
  1st Tier

  			Target	SEQ
  gRNA	DNA		Site	ID
  Name	Strand	Targeting Domain	Length	NO:
  HBB-93	+	AACGGCAGACUUCUCCAC		18	16085
  HBB-94	+	UAACGGCAGACUUCUCCAC		19	16086
  HBB-2	+	GUAACGGCAGACUUCUCCAC		20	16087
  HBB-95	+	AGUAACGGCAGACUUCUCCAC		21	16088
  HBB-96	+	CAGUAACGGCAGACUUCUCCAC		22	16089
  HBB-97	+	GCAGUAACGGCAGACUUCUCCAC		23	16090
  HBB-98	+	GGCAGUAACGGCAGACUUCUCCAC		24	16091
  HBB-99	−	CUGUGGGGCAAGGUGAAC	18	16092
  HBB-100	−	CCUGUGGGGCAAGGUGAAC	19	16093
  HBB-101	−	CCCUGUGGGGCAAGGUGAAC	20	16094
  HBB-102	−	GCCCUGUGGGGCAAGGUGAAC	21	16095
  HBB-103	−	UGCCCUGUGGGGCAAGGUGAAC	22	16096
  HBB-104	−	CUGCCCUGUGGGGCAAGGUGAAC	23	16097
  HBB-105	−	ACUGCCCUGUGGGGCAAGGUGAAC	24	16098

• Table 25B provides exemplary targeting domains for correcting a mutation (e.g., E6V) in the HBB gene selected according to the fourth tier parameters. The targeting domains bind within 200 bp to a mutation (e.g., E6V), and the PAM is NNGRRV. 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 25B
  4th Tier

  			Target	SEQ
  gRNA	DNA		Site	ID
  Name	Strand	Targeting Domain	Length	NO:
  HBB-106	+	CACGUUCACCUUGCCCCA	18	16099
  HBB-107	+	CCACGUUCACCUUGCCCCA	19	16100
  HBB-58	+	UCCACGUUCACCUUGCCCCA	20	16101
  HBB-108	+	AUCCACGUUCACCUUGCCCCA	21	16102
  HBB-109	+	CAUCCACGUUCACCUUGCCCCA	22	16103
  HBB-110	+	UCAUCCACGUUCACCUUGCCCCA	23	16104
  HBB-111	+	UUCAUCCACGUUCACCUUGCCCCA	24	16105
  HBB-112	+	UAACGGCAGACUUCUCCA	18	16106
  HBB-113	+	GUAACGGCAGACUUCUCCA	19	16107
  HBB-69	+	AGUAACGGCAGACUUCUCCA	20	16108
  HBB-114	+	CAGUAACGGCAGACUUCUCCA	21	16109
  HBB-115	+	GCAGUAACGGCAGACUUCUCCA	22	16110
  HBB-116	+	GGCAGUAACGGCAGACUUCUCCA	23	16111
  HBB-117	+	GGGCAGUAACGGCAGACUUCUCCA	24	16112
  HBB-118	+	GUCUGUUUGAGGUUGCUA	18	16113
  HBB-119	+	UGUCUGUUUGAGGUUGCUA	19	16114
  HBB-66	+	GUGUCUGUUUGAGGUUGCUA	20	16115
  HBB-120	+	GGUGUCUGUUUGAGGUUGCUA	21	16116
  HBB-121	+	UGGUGUCUGUUUGAGGUUGCUA	22	16117
  HBB-122	+	AUGGUGUCUGUUUGAGGUUGCUA	23	16118
  HBB-123	+	CAUGGUGUCUGUUUGAGGUUGCUA	24	16119
  HBB-124	+	CCUUGAUACCAACCUGCC	18	16120
  HBB-125	+	ACCUUGAUACCAACCUGCC	19	16121
  HBB-57	+	AACCUUGAUACCAACCUGCC	20	16122
  HBB-126	+	UAACCUUGAUACCAACCUGCC	21	16123
  HBB-127	+	GUAACCUUGAUACCAACCUGCC	22	16124
  HBB-128	+	UGUAACCUUGAUACCAACCUGCC	23	16125
  HBB-129	+	UUGUAACCUUGAUACCAACCUGCC	24	16126
  HBB-130	+	GUGCACCAUGGUGUCUGU	18	16127
  HBB-131	+	GGUGCACCAUGGUGUCUGU	19	16128
  HBB-62	+	AGGUGCACCAUGGUGUCUGU	20	16129
  HBB-132	+	CAGGUGCACCAUGGUGUCUGU	21	16130
  HBB-133	+	UCAGGUGCACCAUGGUGUCUGU	22	16131
  HBB-134	+	GUCAGGUGCACCAUGGUGUCUGU	23	16132
  HBB-135	+	AGUCAGGUGCACCAUGGUGUCUGU	24	16133
  HBB-136	+	UAGUGAACACAGUUGUGU	18	16134
  HBB-137	+	CUAGUGAACACAGUUGUGU	19	16135
  HBB-59	+	GCUAGUGAACACAGUUGUGU	20	16136
  HBB-138	+	UGCUAGUGAACACAGUUGUGU	21	16137
  HBB-139	+	UUGCUAGUGAACACAGUUGUGU	22	16138
  HBB-140	+	GUUGCUAGUGAACACAGUUGUGU	23	16139
  HBB-141	+	GGUUGCUAGUGAACACAGUUGUGU	24	16140
  HBB-142	−	UAAGGAGACCAAUAGAAA	18	16141
  HBB-143	−	UUAAGGAGACCAAUAGAAA	19	16142
  HBB-144	−	UUUAAGGAGACCAAUAGAAA	20	16143
  HBB-145	−	GUUUAAGGAGACCAAUAGAAA	21	16144
  HBB-146	−	GGUUUAAGGAGACCAAUAGAAA	22	16145
  HBB-147	−	AGGUUUAAGGAGACCAAUAGAAA	23	16146
  HBB-148	−	CAGGUUUAAGGAGACCAAUAGAAA	24	16147
  HBB-149	−	CAGGUUUAAGGAGACCAA	18	16148
  HBB-150	−	ACAGGUUUAAGGAGACCAA	19	16149
  HBB-151	−	GACAGGUUUAAGGAGACCAA	20	16150
  HBB-152	−	AGACAGGUUUAAGGAGACCAA	21	16151
  HBB-153	−	AAGACAGGUUUAAGGAGACCAA	22	16152
  HBB-154	−	CAAGACAGGUUUAAGGAGACCAA	23	16153
  HBB-155	−	ACAAGACAGGUUUAAGGAGACCAA	24	16154
  HBB-156	−	GGUUACAAGACAGGUUUA	18	16155
  HBB-157	−	AGGUUACAAGACAGGUUUA	19	16156
  HBB-80	−	AAGGUUACAAGACAGGUUUA	20	16157
  HBB-158	−	CAAGGUUACAAGACAGGUUUA	21	16158
  HBB-159	−	UCAAGGUUACAAGACAGGUUUA	22	16159
  HBB-160	−	AUCAAGGUUACAAGACAGGUUUA	23	16160
  HBB-161	−	UAUCAAGGUUACAAGACAGGUUUA	24	16161
  HBB-162	−	GAAGUUGGUGGUGAGGCC	18	16162
  HBB-163	−	UGAAGUUGGUGGUGAGGCC	19	16163
  HBB-68	−	AUGAAGUUGGUGGUGAGGCC	20	16164
  HBB-164	−	GAUGAAGUUGGUGGUGAGGCC	21	16165
  HBB-165	−	GGAUGAAGUUGGUGGUGAGGCC	22	16166
  HBB-166	−	UGGAUGAAGUUGGUGGUGAGGCC	23	16167
  HBB-167	−	GUGGAUGAAGUUGGUGGUGAGGCC	24	16168
  HBB-168	−	ACUGCCCUGUGGGGCAAG	18	16169
  HBB-169	−	UACUGCCCUGUGGGGCAAG	19	16170
  HBB-65	−	UUACUGCCCUGUGGGGCAAG	20	16171
  HBB-170	−	GUUACUGCCCUGUGGGGCAAG	21	16172
  HBB-171	−	CGUUACUGCCCUGUGGGGCAAG	22	16173
  HBB-172	−	CCGUUACUGCCCUGUGGGGCAAG	23	16174
  HBB-173	−	GCCGUUACUGCCCUGUGGGGCAAG	24	16175
  HBB-174	−	GGAGGGCAGGAGCCAGGG	18	16176
  HBB-175	−	GGGAGGGCAGGAGCCAGGG	19	16177
  HBB-176	−	AGGGAGGGCAGGAGCCAGGG	20	16178
  HBB-177	−	CAGGGAGGGCAGGAGCCAGGG	21	16179
  HBB-178	−	GCAGGGAGGGCAGGAGCCAGGG	22	16180
  HBB-179	−	AGCAGGGAGGGCAGGAGCCAGGG	23	16181
  HBB-180	−	GAGCAGGGAGGGCAGGAGCCAGGG	24	16182
  HBB-181	−	UGGGCAUAAAAGUCAGGG	18	16183
  HBB-182	−	CUGGGCAUAAAAGUCAGGG	19	16184
  HBB-183	−	GCUGGGCAUAAAAGUCAGGG	20	16185
  HBB-184	−	GGCUGGGCAUAAAAGUCAGGG	21	16186
  HBB-185	−	GGGCUGGGCAUAAAAGUCAGGG	22	16187
  HBB-186	−	AGGGCUGGGCAUAAAAGUCAGGG	23	16188
  HBB-187	−	CAGGGCUGGGCAUAAAAGUCAGGG	24	16189
  HBB-188	−	GGGGCAAGGUGAACGUGG	18	16190
  HBB-189	−	UGGGGCAAGGUGAACGUGG	19	16191
  HBB-67	−	GUGGGGCAAGGUGAACGUGG	20	16192
  HBB-190	−	UGUGGGGCAAGGUGAACGUGG	21	16193
  HBB-191	−	CUGUGGGGCAAGGUGAACGUGG	22	16194
  HBB-192	−	CCUGUGGGGCAAGGUGAACGUGG	23	16195
  HBB-193	−	CCCUGUGGGGCAAGGUGAACGUGG	24	16196
  HBB-194	−	UCUGCCGUUACUGCCCUG	18	16197
  HBB-195	−	GUCUGCCGUUACUGCCCUG	19	16198
  HBB-27	−	AGUCUGCCGUUACUGCCCUG	20	16199
  HBB-196	−	AAGUCUGCCGUUACUGCCCUG	21	16200
  HBB-197	−	GAAGUCUGCCGUUACUGCCCUG	22	16201
  HBB-198	−	AGAAGUCUGCCGUUACUGCCCUG	23	16202
  HBB-199	−	GAGAAGUCUGCCGUUACUGCCCUG	24	16203
  HBB-200	−	UGGUGCACCUGACUCCUG	18	16204
  HBB-201	−	AUGGUGCACCUGACUCCUG	19	16205
  HBB-6	−	CAUGGUGCACCUGACUCCUG	20	16206
  HBB-202	−	CCAUGGUGCACCUGACUCCUG	21	16207
  HBB-203	−	ACCAUGGUGCACCUGACUCCUG	22	16208
  HBB-204	−	CACCAUGGUGCACCUGACUCCUG	23	16209
  HBB-205	−	ACACCAUGGUGCACCUGACUCCUG	24	16210
  HBB-206	−	ACGUGGAUGAAGUUGGUG	18	16211
  HBB-207	−	AACGUGGAUGAAGUUGGUG	19	16212
  HBB-64	−	GAACGUGGAUGAAGUUGGUG	20	16213
  HBB-208	−	UGAACGUGGAUGAAGUUGGUG	21	16214
  HBB-209	−	GUGAACGUGGAUGAAGUUGGUG	22	16215
  HBB-210	−	GGUGAACGUGGAUGAAGUUGGUG	23	16216
  HBB-211	−	AGGUGAACGUGGAUGAAGUUGGUG	24	16217
  HBB-212	−	GUGCACCUGACUCCUGUG	18	16218
  HBB-213	−	GGUGCACCUGACUCCUGUG	19	16219
  HBB-63	−	UGGUGCACCUGACUCCUGUG	20	16220
  HBB-214	−	AUGGUGCACCUGACUCCUGUG	21	16221
  HBB-215	−	CAUGGUGCACCUGACUCCUGUG	22	16222
  HBB-216	−	CCAUGGUGCACCUGACUCCUGUG	23	16223
  HBB-217	−	ACCAUGGUGCACCUGACUCCUGUG	24	16224
  HBB-218	−	GUCUGCCGUUACUGCCCU	18	16225
  HBB-219	−	AGUCUGCCGUUACUGCCCU	19	16226
  HBB-56	−	AAGUCUGCCGUUACUGCCCU	20	16227
  HBB-220	−	GAAGUCUGCCGUUACUGCCCU	21	16228
  HBB-221	−	AGAAGUCUGCCGUUACUGCCCU	22	16229
  HBB-222	−	GAGAAGUCUGCCGUUACUGCCCU	23	16230
  HBB-223	−	GGAGAAGUCUGCCGUUACUGCCCU	24	16231
  HBB-224	−	AUGGUGCACCUGACUCCU	18	16232
  HBB-225	−	CAUGGUGCACCUGACUCCU	19	16233
  HBB-60	−	CCAUGGUGCACCUGACUCCU	20	16234
  HBB-226	−	ACCAUGGUGCACCUGACUCCU	21	16235
  HBB-227	−	CACCAUGGUGCACCUGACUCCU	22	16236
  HBB-228	−	ACACCAUGGUGCACCUGACUCCU	23	16237
  HBB-229	−	GACACCAUGGUGCACCUGACUCCU	24	16238
  HBB-230	−	AGGGCUGGGCAUAAAAGU	18	16239
  HBB-231	−	CAGGGCUGGGCAUAAAAGU	19	16240
  HBB-232	−	CCAGGGCUGGGCAUAAAAGU	20	16241
  HBB-233	−	GCCAGGGCUGGGCAUAAAAGU	21	16242
  HBB-234	−	AGCCAGGGCUGGGCAUAAAAGU	22	16243
  HBB-235	−	GAGCCAGGGCUGGGCAUAAAAGU	23	16244
  HBB-236	−	GGAGCCAGGGCUGGGCAUAAAAGU	24	16245
  HBB-237	−	AGGUUACAAGACAGGUUU	18	16246
  HBB-238	−	AAGGUUACAAGACAGGUUU	19	16247
  HBB-239	−	CAAGGUUACAAGACAGGUUU	20	16248
  HBB-240	−	UCAAGGUUACAAGACAGGUUU	21	16249
  HBB-241	−	AUCAAGGUUACAAGACAGGUUU	22	16250
  HBB-242	−	UAUCAAGGUUACAAGACAGGUUU	23	16251
  HBB-243	−	GUAUCAAGGUUACAAGACAGGUUU	24	16252

• Table 26 provides exemplary targeting domains for correcting a mutation (e.g., E6V) in the HBB gene selected according to the first tier parameters. The targeting domains bind within 200 bp to a mutation (e.g., E6V) and have a high level of orthogonality. 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).

• TABLE 26
  1st Tier

  			Target	SEQ
  gRNA	DNA		Site	ID
  Name	Strand	Targeting Domain	Length	NO:
  HBB-244	−	AGCCAUCUAUUGCUUAC	17	16253
  HBB-245	−	GUCAGGGCAGAGCCAUC	17	16254
  HBB-246	−	CAGAGCCAUCUAUUGCUUAC	20	16255
  HBB-247	−	AAAGUCAGGGCAGAGCCAUC	20	16256

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, Pasteurella multocida, Phascolarctobacterium succinatutens, Ralstonia syzygii, Rhodopseudomonas palustris, Rhodovulum sp., Simonsiella muelleri, Sphingomonas sp., Sporolactobacillus vineae, Staphylococcus lugdunensis, Streptococcus sp., Subdoligranulum sp., Tistrella mobilis, Treponema sp., or Verminephrobacter eiseniae.
• A Cas9 molecule, or Cas9 polypeptide, as that term is used herein, refers to a molecule or 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 28.
• 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/nature13579).
• 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 REC1 domain, and the REC2 domain. The REC lobe does not share structural similarity with other known proteins, indicating that it is a Cas9-specific functional domain. The BH domain is a long c helix and arginine rich region and comprises amino acids 60-93 of the sequence of S. pyogenes Cas9. The REC1 domain is important for recognition of the repeat:anti-repeat duplex, e.g., of a gRNA or a tracrRNA, and is therefore critical for Cas9 activity by recognizing the target sequence. The REC1 domain comprises two REC1 motifs at amino acids 94 to 179 and 308 to 717 of the sequence of S. pyogenes Cas9. These two REC1 domains, though separated by the REC2 domain in the linear primary structure, assemble in the tertiary structure to form the REC1 domain. The REC2 domain, or parts thereof, may also play a role in the recognition of the repeat:anti-repeat duplex. The REC2 domain comprises amino acids 180-307 of the sequence of S. pyogenes Cas9.
• The NUC lobe comprises the RuvC domain, 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:

• 	(SEQ ID NO: 8)
  	D-X1-G-X2-X3-X4-X5-G-X6-X7-X8-X9,

• wherein,
• X1 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 A).
• 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:

• 	(SEQ ID NO: 9)
  	D-X1-G-X2-X3-S-X5-G-X6-X7-X8-X9,,

• wherein
• X1 is selected from I, V, M, L and T (e.g., selected from I, V, and L);
• X2 is selected from T, I, V, S, N, Y, E and L (e.g., selected from T, V, and I);
• X3 is selected from N, S, G, A, D, T, R, M and F (e.g., A or N);
• X5 is selected from V, I, L, C, T and F (e.g., selected from V, I and L);
• X6 is selected from W, F, V, Y, S and L (e.g., W);
• X7 is selected from A, S, C, V and G (e.g., selected from A and S);
• X8 is selected from V, I, L, A, M and H (e.g., selected from V, I, M and L); and
• X9 is selected from any amino acid or is absent (e.g., selected from T, V, I, L, Δ, F, S, A,
• Y, M and R or selected from e.g., T, V, I, L and A).
• 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:

• 	(SEQ ID NO: 10)
  	D-I-G-X2-X3-S-V-G-W-A-X8-X9,

• wherein
• X2 is selected from T, I, V, S, N, Y, E and L (e.g., selected from T, V, and I);
• X3 is selected from N, S, G, A, D, T, R, M and F (e.g., A or N);
• X8 is selected from V, I, L, A, M and H (e.g., selected from V, I, M and L); and
• X9 is selected from any amino acid or is absent (e.g., selected from T, V, I, L, Δ, F, S, A, Y, M and R or selected from e.g., T, V, I, L and Δ).
• In an embodiment, the N-terminal RuvC-like domain differs from a sequence of SEQ ID NO:10 by as many as 1 but no more than, 2, 3, 4, or 5 residues.
• In an embodiment, the N-terminal RuvC-like domain comprises an amino acid sequence of formula III:

• 	(SEQ ID NO: 11)
  	D-I-G-T-N-S-V-G-W-A-V-X,

• 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:

• 	(SEQ ID NO: 12)
  	I-X1-X2-E-X3-A-R-E,

  
  wherein
• X1 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:

• 	(SEQ ID NO: 13)
  	I-V-X2-E-M-A-R-E,

  
  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:

• 	(SEQ ID NO: 14)
  	H-H-A-X1-D-A-X2-X3,

  
  wherein
• X1 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:

• 	(SEQ ID NO: 15)
  	H-H-A-H-D-A-Y-L.

• 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:

• 	(SEQ ID NO: 16)
  	K-X1′-Y-X2′-X3′-X4′-Z-T-D-X9′-Y,.

• wherein
• X1′ 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:

• (SEQ ID NO: 17)

  X1-X2-X3-H-X4-X5-P-X6-X7-X8-X9-X10-X11-X12-X13-

  X14-X15-N-X16-X17-X18-X19-X20-X21-X22-X23-N,

  
  wherein
• X1 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;
• X11 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:

• (SEQ ID NO: 18)

  X1-X2-X3-H-X4-X5-P-X6-S-X8-X9-X10-D-D-S-X14-X15-

  N-K-V-L-X19-X20-X21-X22-X23-N,

• wherein
• X1 is selected from D and E;
• X2 is selected from L, I, R, Q, V, M and K;
• X3 is selected from D and E;
• X4 is selected from I, V, T, A and L (e.g., A, I and V);
• X5 is selected from V, Y, I, L, F and W (e.g., V, I and L);
• X6 is selected from Q, H, R, K, Y, I, L, F and W;
• X8 is selected from F, L, V, K, Y, M, I, R, A, E, D and Q (e.g., F);
• X9 is selected from L, R, T, I, V, S, C, Y, K, F and G;
• X10 is selected from K, Q, Y, T, F, L, W, M, A, E, G, and S;
• X14 is selected from I, L, F, S, R, Y, Q, W, D, K and H (e.g., I, L and F);
• X15 is selected from D, S, I, N, E, A, H, F, L, Q, M, G, Y and V;
• X19 is selected from T, V, C, E, S and A (e.g., T and V);
• X20 is selected from R, F, T, W, E, L, N, C, K, V, S, Q, I, Y, H and A;
• X21 is selected from S, P, R, K, N, A, H, Q, G and L;
• X22 is selected from D, G, T, N, S, K, A, I, E, L, Q, R and Y; and
• X23 is selected from K, V, A, E, Y, I, C, L, S, T, G, K, M, D and F.
• In an embodiment, the HNH-like domain differs from a sequence of SEQ ID NO: 18 by 1, 2, 3, 4, or 5 residues.
• In an embodiment, an eaCas9 molecule or eaCas9 polypeptide comprises an HNH-like domain comprising an amino acid sequence of formula VII:

• (SEQ ID NO: 19)

  X1-V-X3-H-I-V-P-X6-S-X8-X9-X10-D-D-S-X14-X15-N-K-

  V-L-T-X20-X21-X22-X23-N,

• wherein
• X1 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:

• (SEQ ID NO: 20)

  D-X2-D-H-I-X5-P-Q-X7-F-X9-X10-D-X12-S-I-D-N-X16-

  V-L-X19-X20-S-X22-X23-N,

• 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:

• (SEQ ID NO: 21)

  L-Y-Y-L-Q-N-G-X1’-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,

• wherein
• X1′ 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;
• X7′ 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;
• X11′ 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 polypeptide 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 eaCas9 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 al., 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 (SEQ ID NO.: 94) or NNNGCTT (R=A or G) (SEQ ID NO: 95) 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. equines (e.g., strain ATCC 9812, MGCS 124), S. dysdalactiae (e.g., strain GGS 124), S. bovis (e.g., strain ATCC 700338), S. anginosus (e.g., strain F0211), S. agalactiae (e.g., strain NEM316, A909), Listeria monocytogenes (e.g., strain F6854), Listeria innocua (L. innocua, e.g., strain Clip11262), 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 (residues1 to 180, or in the case of region 1'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 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.
• 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 wildtype, 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 fixed sequence of the consensus sequence disclosed in FIGS. 2A-2G differs at no more than 1, 2, 3, 4, 5, 10, 15, or 20% of the fixed residues in the consensus sequence disclosed in FIGS. 2A-2G;
• the sequence corresponding to the residues identified by “*” in the consensus sequence disclosed in FIGS. 2A-2G differ at no more than 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, or 40% of the “*” residues from the corresponding sequence of naturally occurring Cas9 molecule, e.g., an S. thermophilus Cas9 molecule; and,
• the sequence corresponding to the residues identified by “-” in the consensus sequence disclosed in FIGS. 2A-2G differ at no more than 5, 10, 15, 20, 25, 30, 35, 40, 45, 55, or 60% of the “-” residues from the corresponding sequence of naturally occurring Cas9 molecule, e.g., an S. thermophilus Cas9 molecule.
• In an embodiment, the altered Cas9 molecule or Cas9 polypeptide is an eaCas9 molecule or eaCas9 polypeptide comprising the fixed amino acid residues of S. mutans shown in the consensus sequence disclosed in FIGS. 2A-2G, and has one or more amino acids that differ from the amino acid sequence of S. mutans (e.g., has a substitution) at one or more residue (e.g., 2, 3, 5, 10, 15, 20, 30, 50, 70, 80, 90, 100, 200 amino acid residues) represented by an “-” in the consensus sequence disclosed in FIGS. 2A-2G.
• In an embodiment, the altered Cas9 molecule or Cas9 polypeptide comprises a sequence in which:
• the sequence corresponding to the fixed sequence of the consensus sequence disclosed in FIGS. 2A-2G differs at no more than 1, 2, 3, 4, 5, 10, 15, or 20% of the fixed residues in the consensus sequence disclosed in FIGS. 2A-2G;
• the sequence corresponding to the residues identified by “*” in the consensus sequence disclosed in FIGS. 2A-2G differ at no more than 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, or 40% of the “*” residues from the corresponding sequence of naturally occurring Cas9 molecule, e.g., an S. mutans Cas9 molecule; and,
• the sequence corresponding to the residues identified by “-” in the consensus sequence disclosed in FIGS. 2A-2G differ at no more than 5, 10, 15, 20, 25, 30, 35, 40, 45, 55, or 60% of the “-” residues from the corresponding sequence of naturally occurring Cas9 molecule, e.g., an S. mutans Cas9 molecule.
• In an embodiment, the altered Cas9 molecule or Cas9 polypeptide is an eaCas9 molecule or eaCas9 polypeptide comprising the fixed amino acid residues of L. innocula shown in the consensus sequence disclosed in FIGS. 2A-2G, and has one or more amino acids that differ from the amino acid sequence of L. innocula (e.g., has a substitution) at one or more residue (e.g., 2, 3, 5, 10, 15, 20, 30, 50, 70, 80, 90, 100, 200 amino acid residues) represented by an “-” in the consensus sequence disclosed in FIGS. 2A-2G.
• In an embodiment, the altered Cas9 molecule or Cas9 polypeptide comprises a sequence in which:
• the sequence corresponding to the fixed sequence of the consensus sequence disclosed in FIGS. 2A-2G differs at no more than 1, 2, 3, 4, 5, 10, 15, or 20% of the fixed residues in the consensus sequence disclosed in FIGS. 2A-2G;
• the sequence corresponding to the residues identified by “*” in the consensus sequence disclosed in FIGS. 2A-2G differ at no more than 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, or 40% of the “*” residues from the corresponding sequence of naturally occurring Cas9 molecule, e.g., an L. innocula Cas9 molecule; and,
• the sequence corresponding to the residues identified by “-” in the consensus sequence disclosed in FIGS. 2A-2G differ at no more than 5, 10, 15, 20, 25, 30, 35, 40, 45, 55, or 60% of the “-” residues from the corresponding sequence of naturally occurring Cas9 molecule, e.g., an L. innocula Cas9 molecule.
• In an embodiment, the altered Cas9 molecule or Cas9 polypeptide, e.g., an eaCas9 molecule or eaCas9 polypeptide, can be a fusion, e.g., of two of more different Cas9 molecules, e.g., of two or more naturally occurring Cas9 molecules of different species. For example, a fragment of a naturally occurring Cas9 molecule of one species can be fused to a fragment of a Cas9 molecule of a second species. As an example, a fragment of a Cas9 molecule of S. pyogenes comprising an N-terminal RuvC-like domain can be fused to a fragment of 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 polypeptide that comprises a Cas9 core domain from one bacterial species and a functional altered PI domain, i.e., a PI domain other than that naturally associated with the Cas9 core domain, e.g., from a different bacterial species.
• In an embodiment, the altered PI domain recognizes a PAM sequence that is different from the PAM sequence recognized by the naturally-occurring Cas9 from which the Cas9 core domain is derived. In an embodiment, the altered PI domain recognizes the same PAM sequence recognized by the naturally-occurring Cas9 from which the Cas9 core domain is derived, but with different affinity or specificity. A Syn-Cas9 molecule or Syn-Cas9 polypetide can be, respectively, a Syn-eaCas9 molecule or Syn-eaCas9 polypeptide or a Syn-eiCas9 molecule Syn-eiCas9 polypeptide.
• An exemplary Syn-Cas9 molecule Syn-Cas9 polypetide comprises:
• a) a Cas9 core domain, e.g., a Cas9 core domain from Table 28 or 29, 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 31 and 32.
• 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 28 and said altered PI domain comprises a PI domain from a species Y Cas9 from Table 28.
• 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 28.
• 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 28.
• 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 32.
• 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 32.
• 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 32.
• 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 31 and 32. The sequences for the 83 Cas9 orthologs referenced in Tables 31 and 32 are provided in Table 28. Table 30 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 a Cas9 molecule or Cas9 polypeptide comprising a deletion that reduces the size of the molecule while still retaining desired Cas9 properties, e.g., essentially native conformation, Cas9 nuclease activity, and/or target nucleic acid molecule recognition. Provided herein are Cas9 molecules or Cas9 polypeptides comprising one or more deletions and optionally one or more linkers, wherein a linker is disposed between the amino acid residues that flank the deletion. Methods for identifying suitable deletions in a reference Cas9 molecule, methods for generating Cas9 molecules with a deletion and a linker, and methods for using such Cas9 molecules will be apparent to one of ordinary skill in the art upon review of this document.
• A Cas9 molecule, e.g., a S. aureus, S. pyogenes, or C. jejuni, Cas9 molecule, having a deletion is smaller, e.g., has reduced number of amino acids, than the corresponding naturally-occurring Cas9 molecule. The smaller size of the Cas9 molecules allows increased flexibility for 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 28, 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 REC1_CT deletion; or
  • iii) a REC1_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 REC1C_T deletion. A Cas9 molecule can comprise a REC2 deletion and a REC1_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 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 28, 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 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 28, 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 28, 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, Wis.), 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 28.
• The amino acid sequences of exemplary Cas9 molecules from different bacterial species are shown below.

• TABLE 28
  Amino Add Sequence of Cas9 Orthologs

  REC2

  REC1CT

  Recsub

  		start	stop		start	stop		start	stop
  	Amino acid	(AA	(AA	# AA	(AA	(AA	# AA	(AA	(AA	# AA
  Species/Composite ID	sequence	pos)	pos)	deleted (n)	pos)	pos)	deleted (n)	pos)	pos)	deleted (n)

  Staphylococcus Aureus	SEQ ID NO:	126	166	41	296	352	57	296	352	57
  tr|J7RUA5|J7RUA5_STAAU	304
  Streptococcus Pyogenes	SEQ ID NO:	176	314	139	511	592	82	511	592	82
  sp|Q99ZW2|CAS9_STRP1	305
  Campylobacter jejuni NCTC	SEQ ID NO:	137	181	45	316	360	45	316	360	45
  11168	306
  gi|218563121|ref|YP_002344900.1
  Bacteroides fragilis NCTC 9343	SEQ ID NO:	148	339	192	524	617	84	524	617	84
  gi|60683389|ref|YP_213533.1|	307
  Bifidobacterium bifidum S17	SEQ ID NO:	173	335	163	516	607	87	516	607	87
  gi|310286728|ref|YP_003937986.	308
  Veillonella atypica ACS-134-V-	SEQ ID NO:	185	339	155	574	663	79	574	663	79
  Col7a	309
  gi|303229466|ref|ZP_07316256.1
  Lactobacillus rhamnosus GG	SEQ ID NO:	169	320	152	559	645	78	559	645	78
  gi|258509199|ref|YP_003171950.1	310
  Filifactor alocis ATCC 35896	SEQ ID NO:	166	314	149	508	592	76	508	592	76
  gi|374307738|ref|YP_005054169.1	311
  Oenococcus kitaharae DSM	SEQ ID NO:	169	317	149	555	639	80	555	639	80
  17330	312
  gi|366983953|gb|EHN59352.1|
  Fructobacillus fructosus KCTC	SEQ ID NO:	168	314	147	488	571	76	488	571	76
  3544	313
  gi|339625081|ref|ZP_08660870.1
  Catenibacterium mitsuokai DSM	SEQ ID NO:	173	318	146	511	594	78	511	594	78
  15897	314
  gi|224543312|ref|ZP_03683851.1
  Finegoldia magna ATCC 29328	SEQ ID NO:	168	313	146	452	534	77	452	534	77
  gi|169823755|ref|YP_001691366.1	315
  Coriobacterium glomerans PW2	SEQ ID NO:	175	318	144	511	592	82	511	592	82
  gi|328956315|ref|YP_004373648.1	316
  Eubacterium yurii ATCC 43715	SEQ ID NO:	169	310	142	552	633	76	552	633	76
  gi|306821691|ref|ZP_07455288.1	317
  Peptoniphilus duerdenii ATCC	SEQ ID NO:	171	311	141	535	615	76	535	615	76
  BAA-1640	318
  gi|304438954|ref|ZP_07398877.1
  Acidaminococcus sp. D21	SEQ ID NO:	167	306	140	511	591	75	511	591	75
  gi|227824983|ref|ZP_03989815.1	319
  Lactobacillus farciminis KCTC	SEQ ID NO:	171	310	140	542	621	85	542	621	85
  3681	320
  gi|336394882|ref|ZP_08576281.1
  Streptococcus sanguinis SK49	SEQ ID NO:	185	324	140	411	490	85	411	490	85
  gi|422884106|ref|ZP_16930555.1	321
  Coprococcus catus GD-7	SEQ ID NO:	172	310	139	556	634	76	556	634	76
  gi|291520705|emb|CBK78998.11	322
  Streptococcus mutans UA159	SEQ ID NO:	176	314	139	392	470	84	392	470	84
  gi|24379809|ref|NP_721764.1|	323
  Streptococcus pyogenes M1 GAS	SEQ ID NO:	176	314	139	523	600	82	523	600	82
  gi|13622193|gb|AAK33936.1|	324
  Streptococcus thermophilus	SEQ ID NO:	176	314	139	481	558	81	481	558	81
  LMD-9	325
  gi|116628213|ref|YP_820832.1|
  Fusobacterium nucleatum	SEQ ID NO:	171	308	138	537	614	76	537	614	76
  ATCC49256	326
  gi|34762592|ref|ZP_00143587.1|
  Pianococcus antarcticus DSM	SEQ ID NO:	162	299	138	538	614	94	538	614	94
  14505	327
  gi|389815359|ref|ZP_10206685.1
  Treponema denticola ATCC	SEQ ID NO:	169	305	137	524	600	81	524	600	81
  35405	328
  gi|42525843|ref|NP_970941.1|
  Solobacterium moorei F0204	SEQ ID NO:	179	314	136	544	619	77	544	619	77
  gi|320528778|ref|ZP_08029929.1	329
  Staphylococcus	SEQ ID NO:	164	299	136	531	606	92	531	606	92
  pseudintermedius ED99	330
  gb|323463801|gb|ADX75954.1|
  Flavobacterium branchiophilum	SEQ ID NO:	162	286	125	538	613	63	538	613	63
  FL-15	331
  gi|347536497|ref|YP_004843922.1
  Ignavibacterium album JCM	SEQ ID NO:	223	329	107	357	432	90	357	432	90
  16511	332
  gi|385811609|ref|YP_005848005.1
  Bergeyella zoohelcum ATCC	SEQ ID NO:	165	261	97	529	604	56	529	604	56
  43767	333
  gi|423317190|ref|ZP_17295095.1
  Nitrobacter hamburgensis X14	SEQ ID NO:	169	253	85	536	611	48	536	611	48
  gi|92109262|ref|YP_571550.1|	334
  Odoribacter laneus YIT 12061	SEQ ID NO:	164	242	79	535	610	63	535	610	63
  gi|374384763|ref|ZP_09642280.1	335
  Legionella pneumophila str.	SEQ ID NO:	164	239	76	402	476	67	402	476	67
  Paris	336
  gi|54296138|ref|YP_122507.1|
  Bacteroides sp. 20 3	SEQ ID NO:	198	269	72	530	604	83	530	604	83
  gi|301311869|ref|ZP_07217791.1	337
  Akkermansia muciniphila ATCC	SEQ ID NO:	136	202	67	348	418	62	348	418	62
  BAA-835	338
  gi|187736489|ref|YP_001878601
  Prevotella sp. C561	SEQ ID NO:	184	250	67	357	425	78	357	425	78
  gi|345885718|ref|ZP_08837074.1	339
  Wolinella succinogenes DSM	SEQ ID NO:	157	218	36	401	468	60	401	468	60
  1740	340
  gi|34557932|ref|NP_907747.1|
  Alicyclobacillus hesperidum	SEQ ID NO:	142	196	55	416	482	61	416	482	61
  URH17-3-68	341
  gi|403744858|ref|ZP_10953934.1
  Caenispirillum salinarum AK4	SEQ ID NO:	161	214	54	330	393	68	330	393	68
  gi|427429481|ref|ZP_18919511.1	342
  Eubacterium rectale ATCC	SEQ ID NO:	133	185	53	322	384	60	322	384	60
  33656	343
  gi|238924075|ref|YP_002937591.1
  Mycoplasma synoviae 53	SEQ ID NO:	187	239	53	319	381	80	319	381	80
  gi|71894592|ref|YP_278700.1|	344
  Porphyromonas sp. oral taxon	SEQ ID NO:	150	202	53	309	371	60	309	371	60
  279 str. F0450	345
  gi|402847315|ref|ZP_10895610.1
  Streptococcus thermophilus	SEQ ID NO:	127	178	139	424	486	81	424	486	81
  LMD-9	346
  gi|116627542|ref|YP_820161.1|
  Roseburia inulinivorans DSM	SEQ ID NO:	154	204	51	318	380	69	318	380	69
  16841	347
  gi|225377804|ref|ZP_03755025.1
  Methylosinus trichosporium	SEQ ID NO:	144	193	50	426	488	64	426	488	64
  OB3b	348
  gi|296446027|ref|ZP_06887976.1
  Ruminococcus albus 8	SEQ ID NO:	139	187	49	351	412	55	351	412	55
  gi|325677756|ref|ZP_08157403.1	349
  Bifidobacterium longum	SEQ ID NO:	183	230	48	370	431	44	370	431	44
  DJO10A	350
  gi|189440764|ref|YP_001955845
  Enterococcus faecalis TX0012	SEQ ID NO:	123	170	48	327	387	60	327	387	60
  gi|315149830|gb|EFT93846.1|	351
  Mycoplasma mobile 163K	SEQ ID NO:	179	226	48	314	374	79	314	374	79
  gi|47458868|ref|YP_015730.1|	352
  Actinomyces coleocanis DSM	SEQ ID NO:	147	193	47	358	418	40	358	418	40
  15436	353
  gi|227494853|ref|ZP_03925169.1
  Dinoroseobacter shibae DFL 12	SEQ ID NO:	138	184	47	338	398	48	338	398	48
  gi|159042956|ref|YP_001531750.1	354
  Actinomyces sp. oral taxon 180	SEQ ID NO:	183	228	46	349	409	40	349	409	40
  str. F0310	355
  gi|315605738|ref|ZP_07880770.1
  Alcanivorax sp. W11-5	SEQ ID NO:	139	183	45	344	404	61	344	404	61
  gi|407803669|ref|ZP_11150502.1	356
  Aminomonas paucivorans DSM	SEQ ID NO:	134	178	45	341	401	63	341	401	63
  12260	357
  gi|312879015|ref|ZP_07738815.1
  Mycoplasma cams PG 14	SEQ ID NO:	139	183	45	319	379	76	319	379	76
  gi|384393286|gb|EIE39736.1|	358
  Lactobacillus coryniformis	SEQ ID NO:	141	184	44	328	387	61	328	387	61
  KCTC 3535	359
  gi|336393381|ref|ZP_08574780.1
  Elusimicrobium minutum Pei191	SEQ ID NO:	177	219	43	322	381	47	322	381	47
  gi|187250660|ref|YP_001875142.1	360
  Neisseria meningitidis Z2491	SEQ ID NO:	147	189	43	360	419	61	360	419	61
  gi|218767588|ref|YP_002342100.1	361
  Pasteurella multocida str. Pm70	SEQ ID NO:	139	181	43	319	378	61	319	378	61
  gi|15602992|ref|NP_246064.1|	362
  Rhodovulum sp. PH10	SEQ ID NO:	141	183	43	319	378	48	319	378	48
  gi|402849997|ref|ZP_10898214.1	363
  Eubacterium dolichum DSM	SEQ ID NO:	131	172	42	303	361	59	303	361	59
  3991	364
  gi|160915782|ref|ZP_02077990.1
  Nitratifractor salsuginis DSM	SEQ ID NO:	143	184	42	347	404	61	347	404	61
  16511	365
  gi|319957206|ref|YP_004168469.1
  Rhodospirillum rubrum ATCC	SEQ ID NO:	139	180	42	314	371	55	314	371	55
  11170	366
  gi|83591793|ref|YP_425545.1|
  Clostridium cellulolyticum H10	SEQ ID NO:	137	176	40	320	376	61	320	376	61
  gi|220930482|ref|YP_002507391.1	367
  Helicobacter mustelae 12198	SEQ ID NO:	148	187	40	298	354	48	298	354	48
  gi|291276265|ref|YP_003516037.1	368
  Ilyobacter polytropus DSM 2926	SEQ ID NO:	134	173	40	462	517	63	462	517	63
  gi|310780384|ref|YP_003968716.1	369
  Sphaerochaeta globus str. Buddy	SEQ ID NO:	163	202	40	335	389	45	335	389	45
  gi|325972003|ref|YP_004248194.1	370
  Staphylococcus lugdunensis	SEQ ID NO:	128	167	40	337	391	57	337	391	57
  M23590	371
  gi|315659848|ref|ZP_07912707.1
  Treponema sp. JC4	SEQ ID NO:	144	183	40	328	382	63	328	382	63
  gi|384109266|ref|ZP_10010146.1	372
  uncultured delta proteobacterium	SEQ ID NO:	154	193	40	313	365	55	313	365	55
  HF0070 07E19	373
  gi|297182908|gb|ADI19058.1|
  Alicycliphilus denitrificans K601	SEQ ID NO:	140	178	39	317	366	48	317	366	48
  gi|330822845|ref|YP_004386148.1	374
  Azospirillum sp. B510	SEQ ID NO:	205	243	39	342	389	46	342	389	46
  gi|288957741|ref|YP_003448082.1	375
  Bradyrhizobium sp. BTAi1	SEQ ID NO:	143	181	39	323	370	48	323	370	48
  gi|148255343|ref|YP_001239928.1	376
  Parvibaculum lavamentivorans	SEQ ID NO:	138	176	39	327	374	58	327	374	58
  DS-1	377
  gi|154250555|ref|YP_001411379.1
  Prevotella timonensis CRIS 5C-	SEQ ID NO:	170	208	39	328	375	61	328	375	61
  B1	378
  gi|282880052|ref|ZP_06288774.1
  Bacillus smithii 7 3 47FAA	SEQ ID NO:	134	171	38	401	448	63	401	448	63
  gi|365156657|ref|ZP_09352959.1	379
  Cand. Puniceispirillum marinum	SEQ ID NO:	135	172	38	344	391	53	344	391	53
  IMCC1322	380
  gi|294086111|ref|YP_003552871.1
  Barnesiella intestinihominis YIT	SEQ ID NO:	140	176	37	371	417	60	371	417	60
  11860	381
  gi|404487228|ref|ZP_11022414.1
  Ralstonia syzygii R24	SEQ ID NO:	140	176	37	395	440	50	395	440	50
  gi|344171927|emb|CCA84553.1|	382
  Wolinella succinogenes DSM	SEQ ID NO:	145	180	36	348	392	60	348	392	60
  1740	383
  gi|34557790|ref|NP_907605.1|
  Mycoplasma gallisepticumstr. F	SEQ ID NO:	144	177	34	373	416	71	373	416	71
  gi|284931710|gb|ADC31648.1|	384
  Acidothermus cellulolyticus 11B	SEQ ID NO:	150	182	33	341	380	58	341	380	58
  gi|117929158|ref|YP_873709.1|	385
  Mycoplasma ovipneumoniae	SEQ ID NO:	156	184	29	381	420	62	381	420	62
  SC01	386
  gi|363542550|ref|ZP_09312133.1

• TABLE 29
  Amino Acid Sequence of Cas9 Core Domains

  		Cas9 Start (AA	Cas9 Stop (AA
  	Strain Name	pos)	pos)

  		Start and Stop numbers refer to the
  		sequence in Table 28

  	Staphylococcus Aureus	1	772
  	Streptococcus Pyogenes	1	1099
  	Campulobacter Jejuni	1	741

• TABLE 30
  Identified PAM sequences and corresponding RKR motifs.

  	PAM sequence	RKR motif
  Strain Name	(NA)	(AA)
  Streptococcus pyogenes	NGG	RKR
  Streptococcus mutans	NGG	RKR
  Streptococcus thermophilus A	NGGNG	RYR
  Treponema denticola	NAAAAN	VAK
  Streptococcus thermophilus B	NNAAAAW	IYK
  Campylobacter jejuni	NNNNACA	NLK
  Pasteurella multocida	GNNNCNNA	KDG
  Neisseria meningitidis	NNNNGATT or	IGK
  Staphylococcus aureus	NNGRRV (R = A or G; V = A. G	NDK
  	or C)
  	NNGRRT (R = A or G)

  
  PI domains are provided in Tables 31 and 32.

• TABLE 31
  Altered PI Domains

  	PI Start	PI Stop (AA	Length of	RKR
  Strain Name	(AA pos)	pos)	PI (AA)	motif (AA)

  	Start and Stop numbers
  	refer to the sequences in
  	Table 28

  Alicycliphilus denitrificans K601	837	1029	193	--Y
  Campylobacter jejuni NCTC 11168	741	984	244	-NG
  Helicobacter mustelae 12198	771	1024	254	-NQ

• TABLE 32
  Other Altered PI Domains

  	PI Start	PI Stop	Length	RKR
  	(AA	(AA	of PI	motif
  Strain Name	pos)	pos)	(AA)	(AA)

  	Start and Stop numbers
  	refer to the sequences in
  	Table 28

  Akkermansia muciniphila ATCC BAA-835	871	1101	231	ALK
  Ralstonia syzygii R24	821	1062	242	APY
  Cand. Puniceispirillum marinum IMCC1322	815	1035	221	AYK
  Fructobacillus fructosus KCTC 3544	1074	1323	250	DGN
  Eubacterium yurii ATCC 43715	1107	1391	285	DGY
  Eubacterium dolichum DSM 3991	779	1096	318	DKK
  Dinoroseobacter shibae DFL 12	851	1079	229	DPI
  Clostridium cellulolyticum H10	767	1021	255	EGK
  Pasteurella multocida str. Pm70	815	1056	242	ENN
  Mycoplasma canis PG 14	907	1233	327	EPK
  Porphyromonas sp. oral taxon 279 str. F0450	935	1197	263	EPT
  Filifactor alocis ATCC 35896	1094	1365	272	EVD
  Aminomonas paucivorans DSM 12260	801	1052	252	EVY
  Wolinella succinogenes DSM 1740	1034	1409	376	EYK
  Oenococcus kitaharae DSM 17330	1119	1389	271	GAL
  CoriobacteriumglomeransPW2	1126	1384	259	GDR
  Peptoniphilus duerdenii ATCC BAA-1640	1091	1364	274	GDS
  Bifidobacterium bifidum S17	1138	1420	283	GGL
  Alicyclobacillus hesperidum URH17-3-68	876	1146	271	GGR
  Roseburia inulinivorans DSM 16841	895	1152	258	GGT
  Actinomyces coleocanis DSM 15436	843	1105	263	GKK
  Odoribacter laneus YIT 12061	1103	1498	396	GKV
  Coprococcus catus GD-7	1063	1338	276	GNQ
  Enterococcus faecalis TX0012	829	1150	322	GRK
  Bacillus smithii 7 3 47FAA	809	1088	280	GSK
  Legionella pneumophila str. Paris	1021	1372	352	GTM
  Bacteroides fragilis NCTC 9343	1140	1436	297	IPV
  Mycoplasma ovipneumoniae SC01	923	1265	343	IRI
  Actinomyces sp. oral taxon 180 str. F0310	895	1181	287	KEK
  Treponema sp. JC4	832	1062	231	KIS
  Fusobacteriumnucleatum ATCC49256	1073	1374	302	KKV
  Lactobacillus farciminis KCTC 3681	1101	1356	256	KKV
  Nitratifractor salsuginis DSM 16511	840	1132	293	KMR
  Lactobacillus coryniformis KCTC 3535	850	1119	270	KNK
  Mycoplasma mobile 163K	916	1236	321	KNY
  Flavobacterium branchiophilum FL-15	1182	1473	292	KQK
  Prevotella timonensis CRIS 5C-B1	957	1218	262	KQQ
  Methylosinus trichosporium OB3b	830	1082	253	KRP
  Prevotella sp. C561	1099	1424	326	KRY
  Mycoplasma gallisepticum str. F	911	1269	359	KTA
  Lactobacillus rhamnosus GG	1077	1363	287	KYG
  Wolinella succinogenes DSM 1740	811	1059	249	LPN
  Streptococcus thermophilus LMD-9	1099	1388	290	MLA
  Treponema denticola ATCC 35405	1092	1395	304	NDS
  Bergeyella zoohelcum ATCC 43767	1098	1415	318	NEK
  Veillonella atypica ACS-134-V-Col7a	1107	1398	292	NGF
  Neisseria meningitidis Z2491	835	1082	248	NHN
  Ignavibacterium album JCM 16511	1296	1688	393	NKK
  Ruminococcus albus 8	853	1156	304	NNF
  Streptococcus thermophilus LMD-9	811	1121	311	NNK
  Barnesiella intestinihominis YIT 11860	871	1153	283	NPV
  Azospirillum sp. B510	911	1168	258	PFH
  Rhodospirillum rubrum ATCC 11170	863	1173	311	PRG
  Pianococcus antarcticus DSM 14505	1087	1333	247	PYY
  Staphylococcus pseudintermedius ED99	1073	1334	262	QIV
  Alcanivorax sp. W11-5	843	1113	271	RIE
  Bradyrhizobium sp. BTAi1	811	1064	254	RIY
  Streptococcus pyogenes M1 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 Pei191	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. PH 10	821	1059	239	VPY
  Bifidobacterium longum DJO10A	904	1187	284	VRK

• Amino acid sequences described in Table 28:
  SEQ ID NO: 304
  MKRNYILGLDIGITSVGYGIIDYETRDVIDAGVRLFKEANVENNEGRRSKRGARRLKRRRRHRI
  QRVKKLLFDYNLLTDHSELSGINPYEARVKGLSQKLSEEEFSAALLHLAKRRGVHNVNEVEEDT
  GNELSTKEQISRNSKALEEKYVAELQLERLKKDGEVRGSINRFKTSDYVKEAKQLLKVQKAYHQ
  LDQSFIDTYIDLLETRRTYYEGPGEGSPFGWKDIKEWYEMLMGHCTYFPEELRSVKYAYNADLY
  NALNDLNNLVITRDENEKLEYYEKFQIIENVFKQKKKPTLKQIAKEILVNEEDIKGYRVTSTGK
  PEFTNLKVYHDIKDITARKEIIENAELLDQIAKILTIYQSSEDIQEELTNLNSELTQEEIEQIS
  NLKGYTGTHNLSLKAINLILDELWHTNDNQIAIFNRLKLVPKKVDLSQQKEIPTTLVDDFILSP
  VVKRSFIQSIKVINAIIKKYGLPNDIIIELAREKNSKDAQKMINEMQKRNRQTNERIEEIIRTT
  GKENAKYLIEKIKLHDMQEGKCLYSLEAIPLEDLLNNPFNYEVDHIIPRSVSFDNSFNNKVLVK
  QEENSKKGNRTPFQYLSSSDSKISYETFKKHILNLAKGKGRISKTKKEYLLEERDINRFSVQKD
  FINRNLVDTRYATRGLMNLLRSYFRVNNLDVKVKSINGGFTSFLRRKWKFKKERNKGYKHHAED
  ALIIANADFIFKEWKKLDKAKKVMENQMFEEKQAESMPEIETEQEYKEIFITPHQIKHIKDFKD
  YKYSHRVDKKPNRELINDTLYSTRKDDKGNTLIVNNLNGLYDKDNDKLKKLINKSPEKLLMYHH
  DPQTYQKLKLIMEQYGDEKNPLYKYYEETGNYLTKYSKKDNGPVIKKIKYYGNKLNAHLDITDD
  YPNSRNKVVKLSLKPYRFDVYLDNGVYKFVTVKNLDVIKKENYYEVNSKCYEEAKKLKKISNQA
  EFIASFYNNDLIKINGELYRVIGVNNDLLNRIEVNMIDITYREYLENMNDKRPPRIIKTIASKT
  QSIKKYSTDILGNLYEVKSKKHPQIIKKG
  SEQ ID NO: 305
  MDKKYSIGLDIGTNSVGWAVITDEYKVPSKKFKVLGNTDRHSIKKNLIGALLFDSGETAEATRL
  KRTARRRYTRRKNRICYLQEIFSNEMAKVDDSFFHRLEESFLVEEDKKHERHPIFGNIVDEVAY
  HEKYPTIYHLRKKLVDSTDKADLRLIYLALAHMIKFRGHFLIEGDLNPDNSDVDKLFIQLVQTY
  NQLFEENPINASGVDAKAILSARLSKSRRLENLIAQLPGEKKNGLFGNLIALSLGLTPNFKSNF
  DLAEDAKLQLSKDTYDDDLDNLLAQIGDQYADLFLAAKNLSDAILLSDILRVNTEITKAPLSAS
  MIKRYDEHHQDLTLLKALVRQQLPEKYKEIFFDQSKNGYAGYIDGGASQEEFYKFIKPILEKMD
  GTEELLVKLNREDLLRKQRTFDNGSIPHQIHLGELHAILRRQEDFYPFLKDNREKIEKILTFRI
  PYYVGPLARGNSRFAWMTRKSEETITPWNFEEVVDKGASAQSFIERMTNFDKNLPNEKVLPKHS
  LLYEYFTVYNELTKVKYVTEGMRKPAFLSGEQKKAIVDLLFKTNRKVTVKQLKEDYFKKIECFD
  SVEISGVEDRFNASLGTYHDLLKIIKDKDFLDNEENEDILEDIVLTLTLFEDREMIEERLKTYA
  HLFDDKVMKQLKRRRYTGWGRLSRKLINGIRDKQSGKTILDFLKSDGFANRNFMQLIHDDSLTF
  KEDIQKAQVSGQGDSLHEHIANLAGSPAIKKGILQTVKVVDELVKVMGRHKPENIVIEMARENQ
  TTQKGQKNSRERMKRIEEGIKELGSQILKEHPVENTQLQNEKLYLYYLQNGRDMYVDQELDINR
  LSDYDVDHIVPQSFLKDDSIDNKVLTRSDKNRGKSDNVPSEEVVKKMKNYWRQLLNAKLITQRK
  FDNLTKAERGGLSELDKAGFIKRQLVETRQITKHVAQILDSRMNTKYDENDKLIREVKVITLKS
  KLVSDFRKDFQFYKVREINNYHHAHDAYLNAVVGTALIKKYPKLESEFVYGDYKVYDVRKMIAK
  SEQEIGKATAKYFEYSNIMNEFKTEITLANGEIRKRPLIETNGETGEIVWDKGRDFATVRKVLS
  MPQVNIVKKTEVQTGGFSKESILPKRNSDKLIARKKDWDPKKYGGFDSPTVAYSVLVVAKVEKG
  KSKKLKSVKELLGITIMERSSFEKNPIDFLEAKGYKEVKKDLIIKLPKYSLFELENGRKRMLAS
  AGELQKGNELALPSKYVNFLYLASHYEKLKGSPEDNEQKQLFVEQHKHYLDEIIEQISEFSKRV
  ILADANLDKVLSAYNKHRDKPIREQAENIIHLFTLTNLGAPAAFKYFDTTIDRKRYTSTKEVLD
  ATLIHQSITGLYETRIDLSQLGGD
  SEQ ID NO: 306
  MARILAFDIGISSIGWAFSENDELKDCGVRIFTKVENPKTGESLALPRRLARSARKRLARRKAR
  LNHLKHLIANEFKLNYEDYQSFDESLAKAYKGSLISPYELRFRALNELLSKQDFARVILHIAKR
  RGYDDIKNSDDKEKGAILKAIKQNEEKLANYQSVGEYLYKEYFQKFKENSKEFTNVRNKKESYE
  RCIAQSFLKDELKLIFKKQREFGFSFSKKFEEEVLSVAFYKRALKDFSHLVGNCSFFTDEKRAP
  KNSPLAFMEVALTRIINLLNNLKNTEGILYTKDDLNALLNEVLKNGTLTYKQTKKLLGLSDDYE
  FKGEKGTYFIEFKKYKEFIKALGEHNLSQDDLNEIAKDITLIKDEIKLKKALAKYDLNQNQIDS
  LSKLEFKDHLNISFKALKLVTPLMLEGKKYDEACNELNLKVAINEDKKDFLPAFNETYYKDEVT
  NPVVLRAIKEYRKVLNALLKKYGKVHKINIELAREVGKNHSQRAKIEKEQNENYKAKKDAELEC
  EKLGLKINSKNILKLRLFKEQKEFCAYSGEKIKISDLQDEKMLEIDHIYPYSRSFDDSYMNKVL
  VFTKQNQEKLNQTPFEAFGNDSAKWQKIEVLAKNLPTKKQKRILDKNYKDKEQKNFKDRNLNDT
  RYIARLVLNYTKDYLDFLPLSDDENTKLNDTQKGSKVHVEAKSGMLTSALRHTWGFSAKDRNNH
  LHHAIDAVIIAYANNSIVKAFSDFKKEQESNSAELYAKKISELDYKNKRKFFEPFSGFRQKVLD
  KIDEIFVSKPERKKPSGALHEETFRKEEEFYQSYGGKEGVLKALELGKIRKVNGKIVKNGDMFR
  VDIFKHKKTNKFYAVPIYTMDFALKVLPNKAVARSKKGEIKDWILMDENYEFCESLYKDSLILI
  QTKDMQEPEFVYYNAFTSSTVSLIVSKHDNKFETLSKNQKILFKNANEKEVIAKSIGIQNLKVF
  EKYIVSALGEVTKAEFRQREDFKK
  SEQ ID NO: 307
  MKRILGLDLGTNSIGWALVNEAENKDERSSIVKLGVRVNPLTVDELTNFEKGKSITTNADRTLK
  RGMRRNLQRYKLRRETLTEVLKEHKLITEDTILSENGNRTTFETYRLRAKAVTEEISLEEFARV
  LLMINKKRGYKSSRKAKGVEEGTLIDGMDIARELYNNNLTPGELCLQLLDAGKKFLPDFYRSDL
  QNELDRIWEKQKEYYPEILTDVLKEELRGKKRDAVWAICAKYFVWKENYTEWNKEKGKTEQQER
  EHKLEGIYSKRKRDEAKRENLQWRVNGLKEKLSLEQLVIVFQEMNTQINNSSGYLGAISDRSKE
  LYFNKQTVGQYQMEMLDKNPNASLRNMVFYRQDYLDEFNMLWEKQAVYHKELTEELKKEIRDII
  IFYQRRLKSQKGLIGFCEFESRQIEVDIDGKKKIKTVGNRVISRSSPLFQEFKIWQILNNIEVT
  VVGKKRKRRKLKENYSALFEELNDAEQLELNGSRRLCQEEKELLAQELFIRDKMTKSEVLKLLF
  DNPQELDLNFKTIDGNKTGYALFQAYSKMIEMSGHEPVDFKKPVEKVVEYIKAVFDLLNWNTDI
  LGFNSNEELDNQPYYKLWHLLYSFEGDNTPTGNGRLIQKMTELYGFEKEYATILANVSFQDDYG
  SLSAKAIHKILPHLKEGNRYDVACVYAGYRHSESSLTREEIANKVLKDRLMLLPKNSLHNPVVE
  KILNQMVNVINVIIDIYGKPDEIRVELARELKKNAKEREELTKSIAQTTKAHEEYKTLLQTEFG
  LTNVSRTDILRYKLYKELESCGYKTLYSNTYISREKLFSKEFDIEHIIPQARLFDDSFSNKTLE
  ARSVNIEKGNKTAYDFVKEKFGESGADNSLEHYLNNIEDLFKSGKISKTKYNKLKMAEQDIPDG
  FIERDLRNTQYIAKKALSMLNEISHRVVATSGSVTDKLREDWQLIDVMKELNWEKYKALGLVEY
  FEDRDGRQIGRIKDWTKRNDHRHHAMDALTVAFTKDVFIQYFNNKNASLDPNANEHAIKNKYFQ
  NGRAIAPMPLREFRAEAKKHLENTLISIKAKNKVITGNINKTRKKGGVNKNMQQTPRGQLHLET
  IYGSGKQYLTKEEKVNASFDMRKIGTVSKSAYRDALLKRLYENDNDPKKAFAGKNSLDKQPIWL
  DKEQMRKVPEKVKIVTLEAIYTIRKEISPDLKVDKVIDVGVRKILIDRLNEYGNDAKKAFSNLD
  KNPIWLNKEKGISIKRVTISGISNAQSLHVKKDKDGKPILDENGRNIPVDFVNTGNNHHVAVYY
  RPVIDKRGQLVVDEAGNPKYELEEVVVSFFEAVTRANLGLPIIDKDYKTTEGWQFLFSMKQNEY
  FVFPNEKTGFNPKEIDLLDVENYGLISPNLFRVQKFSLKNYVFRHHLETTIKDTSSILRGITWI
  DFRSSKGLDTIVKVRVNHIGQIVSVGEY
  SEQ ID NO: 308
  MSRKNYVDDYAISLDIGNASVGWSAFTPNYRLVRAKGHELIGVRLFDPADTAESRRMARTTRRR
  YSRRRWRLRLLDALFDQALSEIDPSFLARRKYSWVHPDDENNADCWYGSVLFDSNEQDKRFYEK
  YPTIYHLRKALMEDDSQHDIREIYLAIHHMVKYRGNFLVEGTLESSNAFKEDELLKLLGRITRY
  EMSEGEQNSDIEQDDENKLVAPANGQLADALCATRGSRSMRVDNALEALSAVNDLSREQRAIVK
  AIFAGLEGNKLDLAKIFVSKEFSSENKKILGIYFNKSDYEEKCVQIVDSGLLDDEEREFLDRMQ
  GQYNAIALKQLLGRSTSVSDSKCASYDAHRANWNLIKLQLRTKENEKDINENYGILVGWKIDSG
  QRKSVRGESAYENMRKKANVFFKKMIETSDLSETDKNRLIHDIEEDKLFPIQRDSDNGVIPHQL
  HQNELKQIIKKQGKYYPFLLDAFEKDGKQINKIEGLLTFRVPYFVGPLVVPEDLQKSDNSENHW
  MVRKKKGEITPWNFDEMVDKDASGRKFIERLVGTDSYLLGEPTLPKNSLLYQEYEVLNELNNVR
  LSVRTGNHWNDKRRMRLGREEKTLLCQRLFMKGQTVTKRTAENLLRKEYGRTYELSGLSDESKF
  TSSLSTYGKMCRIFGEKYVNEHRDLMEKIVELQTVFEDKETLLHQLRQLEGISEADCALLVNTH
  YTGWGRLSRKLLTTKAGECKISDDFAPRKHSIIEIMRAEDRNLMEIITDKQLGFSDWIEQENLG
  AENGSSLMEVVDDLRVSPKVKRGIIQSIRLIDDISKAVGKRPSRIFLELADDIQPSGRTISRKS
  RLQDLYRNANLGKEFKGIADELNACSDKDLQDDRLFLYYTQLGKDMYTGEELDLDRLSSAYDID
  HIIPQAVTQNDSIDNRVLVARAENARKTDSFTYMPQIADRMRNFWQILLDNGLISRVKFERLTR
  QNEFSEREKERFVQRSLVETRQIMKNVATLMRQRYGNSAAVIGLNAELTKEMHRYLGFSHKNRD
  INDYHHAQDALCVGIAGQFAANRGFFADGEVSDGAQNSYNQYLRDYLRGYREKLSAEDRKQGRA
  FGFIVGSMRSQDEQKRVNPRTGEVVWSEEDKDYLRKVMNYRKMLVTQKVGDDFGALYDETRYAA
  TDPKGIKGIPFDGAKQDTSLYGGFSSAKPAYAVLIESKGKTRLVNVTMQEYSLLGDRPSDDELR
  KVLAKKKSEYAKANILLRHVPKMQLIRYGGGLMVIKSAGELNNAQQLWLPYEEYCYFDDLSQGK
  GSLEKDDLKKLLDSILGSVQCLYPWHRFTEEELADLHVAFDKLPEDEKKNVITGIVSALHADAK
  TANLSIVGMTGSWRRMNNKSGYTFSDEDEFIFQSPSGLFEKRVTVGELKRKAKKEVNSKYRTNE
  KRLPTLSGASQP
  SEQ ID NO: 309
  METQTSNQLITSHLKDYPKQDYFVGLDIGTNSVGWAVTNTSYELLKFHSHKMWGSRLFEEGESA
  VTRRGFRSMRRRLERRKLRLKLLEELFADAMAQVDSTFFIRLHESKYHYEDKTTGHSSKHILFI
  DEDYTDQDYFTEYPTIYHLRKDLMENGTDDIRKLFLAVHHILKYRGNFLYEGATFNSNAFTFED
  VLKQALVNITFNCFDTNSAISSISNILMESGKTKSDKAKAIERLVDTYTVFDEVNTPDKPQKEQ
  VKEDKKTLKAFANLVLGLSANLIDLFGSVEDIDDDLKKLQIVGDTYDEKRDELAKVWGDEIHII
  DDCKSVYDAIILMSIKEPGLTISQSKVKAFDKHKEDLVILKSLLKLDRNVYNEMFKSDKKGLHN
  YVHYIKQGRTEETSCSREDFYKYTKKIVEGLADSKDKEYILNEIELQTLLPLQRIKDNGVIPYQ
  LHLEELKVILDKCGPKFPFLHTVSDGFSVTEKLIKMLEFRIPYYVGPLNTHHNIDNGGFSWAVR
  KQAGRVTPWNFEEKIDREKSAAAFIKNLTNKCTYLFGEDVLPKSSLLYSEFMLLNELNNVRIDG
  KALAQGVKQHLIDSIFKQDHKKMTKNRIELFLKDNNYITKKHKPEITGLDGEIKNDLTSYRDMV
  RILGNNFDVSMAEDIITDITIFGESKKMLRQTLRNKFGSQLNDETIKKLSKLRYRDWGRLSKKL
  LKGIDGCDKAGNGAPKTIIELMRNDSYNLMEILGDKFSFMECIEEENAKLAQGQVVNPHDIIDE
  LALSPAVKRAVWQALRIVDEVAHIKKALPSRIFVEVARTNKSEKKKKDSRQKRLSDLYSAIKKD
  DVLQSGLQDKEFGALKSGLANYDDAALRSKKLYLYYTQMGRCAYTGNIIDLNQLNTDNYDIDHI
  YPRSLTKDDSFDNLVLCERTANAKKSDIYPIDNRIQTKQKPFWAFLKHQGLISERKYERLTRIA
  PLTADDLSGFIARQLVETNQSVKATTTLLRRLYPDIDVVFVKAENVSDFRHNNNFIKVRSLNHH
  HHAKDAYLNIVVGNVYHEKFTRNFRLFFKKNGANRTYNLAKMFNYDVICTNAQDGKAWDVKTSM
  NTVKKMMASNDVRVTRRLLEQSGALADATIYKASVAAKAKDGAYIGMKTKYSVFADVTKYGGMT
  KIKNAYSIIVQYTGKKGEEIKEIVPLPIYLINRNATDIELIDYVKSVIPKAKDISIKYRKLCIN
  QLVKVNGFYYYLGGKTNDKIYIDNAIELVVPHDIATYIKLLDKYDLLRKENKTLKASSITTSIY
  NINTSTVVSLNKVGIDVFDYFMSKLRTPLYMKMKGNKVDELSSTGRSKFIKMTLEEQSIYLLEV
  LNLLTNSKTTFDVKPLGITGSRSTIGVKIHNLDEFKIINESITGLYSNEVTIV
  SEQ ID NO: 310
  MTKLNQPYGIGLDIGSNSIGFAVVDANSHLLRLKGETAIGARLFREGQSAADRRGSRTTRRRLS
  RTRWRLSFLRDFFAPHITKIDPDFFLRQKYSEISPKDKDRFKYEKRLFNDRTDAEFYEDYPSMY
  HLRLHLMTHTHKADPREIFLAIHHILKSRGHFLTPGAAKDFNTDKVDLEDIFPALTEAYAQVYP
  DLELTFDLAKADDFKAKLLDEQATPSDTQKALVNLLLSSDGEKEIVKKRKQVLTEFAKAITGLK
  TKFNLALGTEVDEADASNWQFSMGQLDDKWSNIETSMTDQGTEIFEQIQELYRARLLNGIVPAG
  MSLSQAKVADYGQHKEDLELFKTYLKKLNDHELAKTIRGLYDRYINGDDAKPFLREDFVKALTK
  EVTAHPNEVSEQLLNRMGQANFMLKQRTKANGAIPIQLQQRELDQIIANQSKYYDWLAAPNPVE
  AHRWKMPYQLDELLNFHIPYYVGPLITPKQQAESGENVFAWMVRKDPSGNITPYNFDEKVDREA
  SANTFIQRMKTTDTYLIGEDVLPKQSLLYQKYEVLNELNNVRINNECLGTDQKQRLIREVFERH
  SSVTIKQVADNLVAHGDFARRPEIRGLADEKRFLSSLSTYHQLKEILHEAIDDPTKLLDIENII
  TWSTVFEDHTIFETKLAEIEWLDPKKINELSGIRYRGWGQFSRKLLDGLKLGNGHTVIQELMLS
  NHNLMQILADETLKETMTELNQDKLKTDDIEDVINDAYTSPSNKKALRQVLRVVEDIKHAANGQ
  DPSWLFIETADGTGTAGKRTQSRQKQIQTVYANAAQELIDSAVRGELEDKIADKASFTDRLVLY
  FMQGGRDIYTGAPLNIDQLSHYDIDHILPQSLIKDDSLDNRVLVNATINREKNNVFASTLFAGK
  MKATWRKWHEAGLISGRKLRNLMLRPDEIDKFAKGFVARQLVETRQIIKLTEQIAAAQYPNTKI
  IAVKAGLSHQLREELDFPKNRDVNHYHHAFDAFLAARIGTYLLKRYPKLAPFFTYGEFAKVDVK
  KEREFNFIGALTHAKKNIIAKDTGEIVWDKERDIRELDRIYNFKRMLITHEVYFETADLFKQTI
  YAAKDSKERGGSKQLIPKKQGYPTQVYGGYTQESGSYNALVRVAEADTTAYQVIKISAQNASKI
  ASANLKSREKGKQLLNEIVVKQLAKRRKNWKPSANSFKIVIPRFGMGTLFQNAKYGLFMVNSDT
  YYRNYQELWLSRENQKLLKKLFSIKYEKTQMNHDALQVYKAIIDQVEKFFKLYDINQFRAKLSD
  AIERFEKLPINTDGNKIGKTETLRQILIGLQANGTRSNVKNLGIKTDLGLLQVGSGIKLDKDTQ
  IVYQSPSGLFKRRIPLADL
  SEQ ID NO: 311
  MTKEYYLGLDVGTNSVGWAVTDSQYNLCKFKKKDMWGIRLFESANTAKDRRLQRGNRRRLERKK
  QRIDLLQEIFSPEICKIDPTFFIRLNESRLHLEDKSNDFKYPLFIEKDYSDIEYYKEFPTIFHL
  RKHLIESEEKQDIRLIYLALHNIIKTRGHFLIDGDLQSAKQLRPILDTFLLSLQEEQNLSVSLS
  ENQKDEYEEILKNRSIAKSEKVKKLKNLFEISDELEKEEKKAQSAVIENFCKFIVGNKGDVCKF
  LRVSKEELEIDSFSFSEGKYEDDIVKNLEEKVPEKVYLFEQMKAMYDWNILVDILETEEYISFA
  KVKQYEKHKTNLRLLRDIILKYCTKDEYNRMFNDEKEAGSYTAYVGKLKKNNKKYWIEKKRNPE
  EFYKSLGKLLDKIEPLKEDLEVLTMMIEECKNHTLLPIQKNKDNGVIPHQVHEVELKKILENAK
  KYYSFLTETDKDGYSVVQKIESIFRFRIPYYVGPLSTRHQEKGSNVWMVRKPGREDRIYPWNME
  EIIDFEKSNENFITRMTNKCTYLIGEDVLPKHSLLYSKYMVLNELNNVKVRGKKLPTSLKQKVF
  EDLFENKSKVTGKNLLEYLQIQDKDIQIDDLSGFDKDFKTSLKSYLDFKKQIFGEEIEKESIQN
  MIEDIIKWITIYGNDKEMLKRVIRANYSNQLTEEQMKKITGFQYSGWGNFSKMFLKGISGSDVS
  TGETEDIITAMWETDNNLMQILSKKETFMDNVEDENSGKVGKIDKITYDSTVKEMELSPENKRA
  VWQTIQVAEEIKKVMGCEPKKIFIEMARGGEKVKKRTKSRKAQLLELYAACEEDCRELIKEIED
  RDERDFNSMKLFLYYTQFGKCMYSGDDIDINELIRGNSKWDRDHIYPQSKIKDDSIDNLVLVNK
  TYNAKKSNELLSEDIQKKMHSFWLSLLNKKLITKSKYDRLTRKGDFTDEELSGFIARQLVETRQ
  STKAIADIFKQIYSSEVVYVKSSLVSDFRKKPLNYLKSRRVNDYHHAKDAYLNIVVGNVYNKKF
  TSNPIQWMKKNRDTNYSLNKVFEHDVVINGEVIWEKCTYHEDTNTYDGGTLDRIRKIVERDNIL
  YTEYAYCEKGELENATIQNKNGNSTVSLKKGLDVKKYGGYFSANTSYFSLIEFEDKKGDRARHI
  IGVPIYIANMLEHSPSAFLEYCEQKGYQNVRILVEKIKKNSLLIINGYPLRIRGENEVDTSFKR
  AIQLKLDQKNYELVRNIEKFLEKYVEKKGNYPIDENRDHITHEKMNQLYEVLLSKMKKFNKKGM
  ADPSDRIEKSKPKFIKLEDLIDKINVINKMLNLLRCDNDTKADLSLIELPKNAGSFVVKKNTIG
  KSKIILVNQSVTGLYENRREL
  SEQ ID NO: 312
  MARDYSVGLDIGTSSVGWAAIDNKYHLIRAKSKNLIGVRLFDSAVTAEKRRGYRTTRRRLSRRH
  WRLRLLNDIFAGPLTDFGDENFLARLKYSWVHPQDQSNQAHFAAGLLFDSKEQDKDFYRKYPTI
  YHLRLALMNDDQKHDLREVYLAIHHLVKYRGHFLIEGDVKADSAFDVHTFADAIQRYAESNNSD
  ENLLGKIDEKKLSAALTDKHGSKSQRAETAETAFDILDLQSKKQIQAILKSVVGNQANLMAIFG
  LDSSAISKDEQKNYKFSFDDADIDEKIADSEALLSDTEFEFLCDLKAAFDGLTLKMLLGDDKTV
  SAAMVRRFNEHQKDWEYIKSHIRNAKNAGNGLYEKSKKFDGINAAYLALQSDNEDDRKKAKKIF
  QDEISSADIPDDVKADFLKKIDDDQFLPIQRTKNNGTIPHQLHRNELEQIIEKQGIYYPFLKDT
  YQENSHELNKITALINFRVPYYVGPLVEEEQKIADDGKNIPDPTNHWMVRKSNDTITPWNLSQV
  VDLDKSGRRFIERLTGTDTYLIGEPTLPKNSLLYQKFDVLQELNNIRVSGRRLDIRAKQDAFEH
  LFKVQKTVSATNLKDFLVQAGYISEDTQIEGLADVNGKNFNNALTTYNYLVSVLGREFVENPSN
  EELLEEITELQTVFEDKKVLRRQLDQLDGLSDHNREKLSRKHYTGWGRISKKLLTTKIVQNADK
  IDNQTFDVPRMNQSIIDTLYNTKMNLMEIINNAEDDFGVRAWIDKQNTTDGDEQDVYSLIDELA
  GPKEIKRGIVQSFRILDDITKAVGYAPKRVYLEFARKTQESHLTNSRKNQLSTLLKNAGLSELV
  TQVSQYDAAALQNDRLYLYFLQQGKDMYSGEKLNLDNLSNYDIDHIIPQAYTKDNSLDNRVLVS
  NITNRRKSDSSNYLPALIDKMRPFWSVLSKQGLLSKHKFANLTRTRDFDDMEKERFIARSLVET
  RQIIKNVASLIDSHFGGETKAVAIRSSLTADMRRYVDIPKNRDINDYHHAFDALLESTVGQYTE
  NSGLMKKGQLSDSAGNQYNRYIKEWIHAARLNAQSQRVNPFGFVVGSMRNAAPGKLNPETGEIT
  PEENADWSIADLDYLHKVMNFRKITVTRRLKDQKGQLYDESRYPSVLHDAKSKASINFDKHKPV
  DLYGGFSSAKPAYAALIKFKNKFRLVNVLRQWTYSDKNSEDYILEQIRGKYPKAEMVLSHIPYG
  QLVKKDGALVTISSATELHNFEQLWLPLADYKLINTLLKTKEDNLVDILHNRLDLPEMTIESAF
  YKAFDSILSFAFNRYALHQNALVKLQAHRDDFNALNYEDKQQTLERILDALHASPASSDLKKIN
  LSSGFGRLFSPSHFTLADTDEFIFQSVTGLFSTQKTVAQLYQETK
  SEQ ID NO: 313
  MVYDVGLDIGTGSVGWVALDENGKLARAKGKNLVGVRLFDTAQTAADRRGFRTTRRRLSRRKWR
  LRLLDELFSAEINEIDSSFFQRLKYSYVHPKDEENKAHYYGGYLFPTEEETKKFHRSYPTIYHL
  RQELMAQPNKRFDIREIYLAIHHLVKYRGHFLSSQEKITIGSTYNPEDLANAIEVYADEKGLSW
  ELNNPEQLTEIISGEAGYGLNKSMKADEALKLFEFDNNQDKVAIKTLLAGLTGNQIDFAKLFGK
  DISDKDEAKLWKLKLDDEALEEKSQTILSQLTDEEIELFHAVVQAYDGFVLIGLLNGADSVSAA
  MVQLYDQHREDRKLLKSLAQKAGLKHKRFSEIYEQLALATDEATIKNGISTARELVEESNLSKE
  VKEDTLRRLDENEFLPKQRTKANSVIPHQLHLAELQKILQNQGQYYPFLLDTFEKEDGQDNKIE
  ELLRFRIPYYVGPLVTKKDVEHAGGDADNHWVERNEGFEKSRVTPWNFDKVFNRDKAARDFIER
  LTGNDTYLIGEKTLPQNSLRYQLFTVLNELNNVRVNGKKFDSKTKADLINDLFKARKTVSLSAL
  KDYLKAQGKGDVTITGLADESKFNSSLSSYNDLKKTFDAEYLENEDNQETLEKIIEIQTVFEDS
  KIASRELSKLPLDDDQVKKLSQTHYTGWGRLSEKLLDSKIIDERGQKVSILDKLKSTSQNFMSI
  INNDKYGVQAWITEQNTGSSKLTFDEKVNELTTSPANKRGIKQSFAVLNDIKKAMKEEPRRVYL
  EFAREDQTSVRSVPRYNQLKEKYQSKSLSEEAKVLKKTLDGNKNKMSDDRYFLYFQQQGKDMYT
  GRPINFERLSQDYDIDHIIPQAFTKDDSLDNRVLVSRPENARKSDSFAYTDEVQKQDGSLWTSL
  LKSGFINRKKYERLTKAGKYLDGQKTGFIARQLVETRQIIKNVASLIEGEYENSKAVAIRSEIT
  ADMRLLVGIKKHREINSFHHAFDALLITAAGQYMQNRYPDRDSTNVYNEFDRYTNDYLKNLRQL
  SSRDEVRRLKSFGEVVGTMRKGNEDWSEENTSYLRKVMMFKNILTTKKTEKDRGPLNKETIFSP
  KSGKKLIPLNSKRSDTALYGGYSNVYSAYMTLVRANGKNLLIKIPISIANQIEVGNLKINDYIV
  NNPAIKKFEKILISKLPLGQLVNEDGNLIYLASNEYRHNAKQLWLSTTDADKIASISENSSDEE
  LLEAYDILTSENVKNRFPFFKKDIDKLSQVRDEFLDSDKRIAVIQTILRGLQIDAAYQAPVKII
  SKKVSDWHKLQQSGGIKLSDNSEMIYQSATGIFETRVKISDLL
  SEQ ID NO: 314
  IVDYCIGLDLGTGSVGWAVVDMNHRLMKRNGKHLWGSRLFSNAETAANRRASRSIRRRYNKRRE
  RIRLLRAILQDMVLEKDPTFFIRLEHTSFLDEEDKAKYLGTDYKDNYNLFIDEDFNDYTYYHKY
  PTIYHLRKALCESTEKADPRLIYLALHHIVKYRGNFLYEGQKFNMDASNIEDKLSDIFTQFTSF
  NNIPYEDDEKKNLEILEILKKPLSKKAKVDEVMTLIAPEKDYKSAFKELVTGIAGNKMNVTKMI
  LCEPIKQGDSEIKLKFSDSNYDDQFSEVEKDLGEYVEFVDALHNVYSWVELQTIMGATHTDNAS
  ISEAMVSRYNKHHDDLKLLKDCIKNNVPNKYFDMFRNDSEKSKGYYNYINRPSKAPVDEFYKYV
  KKCIEKVDTPEAKQILNDIELENFLLKQNSRTNGSVPYQMQLDEMIKIIDNQAEYYPILKEKRE
  QLLSILTFRIPYYFGPLNETSEHAWIKRLEGKENQRILPWNYQDIVDVDATAEGFIKRMRSYCT
  YFPDEEVLPKNSLIVSKYEVYNELNKIRVDDKLLEVDVKNDIYNELFMKNKTVTEKKLKNWLVN
  NQCCSKDAEIKGFQKENQFSTSLTPWIDFTNIFGKIDQSNFDLIENIIYDLTVFEDKKIMKRRL
  KKKYALPDDKVKQILKLKYKDWSRLSKKLLDGIVADNRFGSSVTVLDVLEMSRLNLMEIINDKD
  LGYAQMIEEATSCPEDGKFTYEEVERLAGSPALKRGIWQSLQIVEEITKVMKCRPKYIYIEFER
  SEEAKERTESKIKKLENVYKDLDEQTKKEYKSVLEELKGFDNTKKISSDSLFLYFTQLGKCMYS
  GKKLDIDSLDKYQIDHIVPQSLVKDDSFDNRVLVVPSENQRKLDDLVVPFDIRDKMYRFWKLLF
  DHELISPKKFYSLIKTEYTERDEERFINRQLVETRQITKNVTQIIEDHYSTTKVAAIRANLSHE
  FRVKNHIYKNRDINDYHHAHDAYIVALIGGFMRDRYPNMHDSKAVYSEYMKMFRKNKNDQKRWK
  DGFVINSMNYPYEVDGKLIWNPDLINEIKKCFYYKDCYCTTKLDQKSGQLFNLTVLSNDAHADK
  GVTKAVVPVNKNRSDVHKYGGFSGLQYTIVAIEGQKKKGKKTELVKKISGVPLHLKAASINEKI
  NYIEEKEGLSDVRIIKDNIPVNQMIEMDGGEYLLTSPTEYVNARQLVLNEKQCALIADIYNAIY
  KQDYDNLDDILMIQLYIELTNKMKVLYPAYRGIAEKFESMNENYVVISKEEKANIIKQMLIVMH
  RGPQNGNIVYDDFKISDRIGRLKTKNHNLNNIVFISQSPTGIYTKKYKL
  SEQ ID NO: 315
  MKSEKKYYIGLDVGTNSVGWAVTDEFYNILRAKGKDLWGVRLFEKADTAANTRIFRSGRRRNDR
  KGMRLQILREIFEDEIKKVDKDFYDRLDESKFWAEDKKVSGKYSLFNDKNFSDKQYFEKFPTIF
  HLRKYLMEEHGKVDIRYYFLAINQMMKRRGHFLIDGQISHVTDDKPLKEQLILLINDLLKIELE
  EELMDSIEEILADVNEKRTDKKNNLKELIKGQDFNKQEGNILNSIEESIVTGKAKIKNIISDED
  ILEKIKEDNKEDFVLTGDSYEENLQYFEEVLQENITLFNTLKSTYDFLILQSILKGKSTLSDAQ
  VERYDEHKKDLEILKKVIKKYDEDGKLFKQVFKEDNGNGYVSYIGYYLNKNKKITAKKKISNIE
  FTKYVKGILEKQCDCEDEDVKYLLGKIEQENFLLKQISSINSVIPHQIHLFELDKILENLAKNY
  PSFNNKKEEFTKIEKIRKTFTFRIPYYVGPLNDYHKNNGGNAWIFRNKGEKIRPWNFEKIVDLH
  KSEEEFIKRMLNQCTYLPEETVLPKSSILYSEYMVLNELNNLRINGKPLDTDVKLKLIEELFKK
  KTKVTLKSIRDYMVRNNFADKEDFDNSEKNLEIASNMKSYIDFNNILEDKFDVEMVEDLIEKIT
  IHTGNKKLLKKYIEETYPDLSSSQIQKIINLKYKDWGRLSRKLLDGIKGTKKETEKTDTVINFL
  RNSSDNLMQIIGSQNYSFNEYIDKLRKKYIPQEISYEVVENLYVSPSVKKMIWQVIRVTEEITK
  VMGYDPDKIFIEMAKSEEEKKTTISRKNKLLDLYKAIKKDERDSQYEKLLTGLNKLDDSDLRSR
  KLYLYYTQMGRDMYTGEKIDLDKLFDSTHYDKDHIIPQSMKKDDSIINNLVLVNKNANQTTKGN
  IYPVPSSIRNNPKIYNYWKYLMEKEFISKEKYNRLIRNTPLTNEELGGFINRQLVETRQSTKAI
  KELFEKFYQKSKIIPVKASLASDLRKDMNTLKSREVNDLHHAHDAFLNIVAGDVWNREFTSNPI
  NYVKENREGDKVKYSLSKDFTRPRKSKGKVIWTPEKGRKLIVDTLNKPSVLISNESHVKKGELF
  NATIAGKKDYKKGKIYLPLKKDDRLQDVSKYGGYKAINGAFFFLVEHTKSKKRIRSIELEPLHL
  LSKFYEDKNTVLDYAINVLQLQDPKIIIDKINYRTEIIIDNFSYLISTKSNDGSITVKPNEQMY
  WRVDEISNLKKIENKYKKDAILTEEDRKIMESYIDKIYQQFKAGKYKNRRTTDTIIEKYEIIDL
  DTLDNKQLYQLLVAFISLSYKTSNNAVDFTVIGLGTECGKPRITNLPDNTYLVYKSITGIYEKR
  IRIK
  SEQ ID NO: 316
  MKLRGIEDDYSIGLDMGTSSVGWAVTDERGTLAHFKRKPTWGSRLFREAQTAAVARMPRGQRRR
  YVRRRWRLDLLQKLFEQQMEQADPDFFIRLRQSRLLRDDRAEEHADYRWPLFNDCKFTERDYYQ
  RFPTIYHVRSWLMETDEQADIRLIYLALHNIVKHRGNFLREGQSLSAKSARPDEALNHLRETLR
  VWSSERGFECSIADNGSILAMLTHPDLSPSDRRKKIAPLFDVKSDDAAADKKLGIALAGAVIGL
  KTEFKNIFGDFPCEDSSIYLSNDEAVDAVRSACPDDCAELFDRLCEVYSAYVLQGLLSYAPGQT
  ISANMVEKYRRYGEDLALLKKLVKIYAPDQYRMFFSGATYPGTGIYDAAQARGYTKYNLGPKKS
  EYKPSESMQYDDFRKAVEKLFAKTDARADERYRMMMDRFDKQQFLRRLKTSDNGSIYHQLHLEE
  LKAIVENQGRFYPFLKRDADKLVSLVSFRIPYYVGPLSTRNARTDQHGENRFAWSERKPGMQDE
  PIFPWNWESIIDRSKSAEKFILRMTGMCTYLQQEPVLPKSSLLYEEFCVLNELNGAHWSIDGDD
  EHRFDAADREGIIEELFRRKRTVSYGDVAGWMERERNQIGAHVCGGQGEKGFESKLGSYIFECK
  DVFKVERLEQSDYPMIERIILWNTLFEDRKILSQRLKEEYGSRLSAEQIKTICKKRFTGWGRLS
  EKFLTGITVQVDEDSVSIMDVLREGCPVSGKRGRAMVMMEILRDEELGFQKKVDDFNRAFFAEN
  AQALGVNELPGSPAVRRSLNQSIRIVDEIASIAGKAPANIFIEVTRDEDPKKKGRRTKRRYNDL
  KDALEAFKKEDPELWRELCETAPNDMDERLSLYFMQRGKCLYSGRAIDIHQLSNAGIYEVDHII
  PRTYVKDDSLENKALVYREENQRKTDMLLIDPEIRRRMSGYWRMLHEAKLIGDKKFRNLLRSRI
  DDKALKGFIARQLVETGQMVKLVRSLLEARYPETNIISVKASISHDLRTAAELVKCREANDFHH
  AHDAFLACRVGLFIQKRHPCVYENPIGLSQVVRNYVRQQADIFKRCRTIPGSSGFIVNSFMTSG
  FDKETGEIFKDDWDAEAEVEGIRRSLNFRQCFISRMPFEDHGVFWDATIYSPRAKKTAALPLKQ
  GLNPSRYGSFSREQFAYFFIYKARNPRKEQTLFEFAQVPVRLSAQIRQDENALERYARELAKDQ
  GLEFIRIERSKILKNQLIEIDGDRLCITGKEEVRNACELAFAQDEMRVIRMLVSEKPVSRECVI
  SLFNRILLHGDQASRRLSKQLKLALLSEAFSEASDNVQRNVVLGLIAIFNGSTNMVNLSDIGGS
  KFAGNVRIKYKKELASPKVNVHLIDQSVTGMFERRTKIGL
  SEQ ID NO: 317
  MENKQYYIGLDVGTNSVGWAVTDTSYNLLRAKGKDMWGARLFEKANTAAERRTKRTSRRRSERE
  KARKAMLKELFADEINRVDPSFFIRLEESKFFLDDRSENNRQRYTLFNDATFTDKDYYEKYKTI
  FHLRSALINSDEKFDVRLVFLAILNLFSHRGHFLNASLKGDGDIQGMDVFYNDLVESCEYFEIE
  LPRITNIDNFEKILSQKGKSRTKILEELSEELSISKKDKSKYNLIKLISGLEASVVELYNIEDI
  QDENKKIKIGFRESDYEESSLKVKEIIGDEYFDLVERAKSVHDMGLLSNIIGNSKYLCEARVEA
  YENHHKDLLKIKELLKKYDKKAYNDMFRKMTDKNYSAYVGSVNSNIAKERRSVDKRKIEDLYKY
  IEDTALKNIPDDNKDKIEILEKIKLGEFLKKQLTASNGVIPNQLQSRELRAILKKAENYLPFLK
  EKGEKNLTVSEMIIQLFEFQIPYYVGPLDKNPKKDNKANSWAKIKQGGRILPWNFEDKVDVKGS
  RKEFIEKMVRKCTYISDEHTLPKQSLLYEKFMVLNEINNIKIDGEKISVEAKQKIYNDLFVKGK
  KVSQKDIKKELISLNIMDKDSVLSGTDTVCNAYLSSIGKFTGVFKEEINKQSIVDMIEDIIFLK
  TVYGDEKRFVKEEIVEKYGDEIDKDKIKRILGFKFSNWGNLSKSFLELEGADVGTGEVRSIIQS
  LWETNFNLMELLSSRFTYMDELEKRVKKLEKPLSEWTIEDLDDMYLSSPVKRMIWQSMKIVDEI
  QTVIGYAPKRIFVEMTRSEGEKVRTKSRKDRLKELYNGIKEDSKQWVKELDSKDESYFRSKKMY
  LYYLQKGRCMYSGEVIELDKLMDDNLYDIDHIYPRSFVKDDSLDNLVLVKKEINNRKQNDPITP
  QIQASCQGFWKILHDQGFMSNEKYSRLTRKTQEFSDEEKLSFINRQIVETGQATKCMAQILQKS
  MGEDVDVVFSKARLVSEFRHKFELFKSRLINDFHHANDAYLNIVVGNSYFVKFTRNPANFIKDA
  RKNPDNPVYKYHMDRFFERDVKSKSEVAWIGQSEGNSGTIVIVKKTMAKNSPLITKKVEEGHGS
  ITKETIVGVKEIKFGRNKVEKADKTPKKPNLQAYRPIKTSDERLCNILRYGGRTSISISGYCLV
  EYVKKRKTIRSLEAIPVYLGRKDSLSEEKLLNYFRYNLNDGGKDSVSDIRLCLPFISTNSLVKI
  DGYLYYLGGKNDDRIQLYNAYQLKMKKEEVEYIRKIEKAVSMSKFDEIDREKNPVLTEEKNIEL
  YNKIQDKFENTVFSKRMSLVKYNKKDLSFGDFLKNKKSKFEEIDLEKQCKVLYNIIFNLSNLKE
  VDLSDIGGSKSTGKCRCKKNITNYKEFKLIQQSITGLYSCEKDLMTI
  SEQ ID NO: 318
  MKNLKEYYIGLDIGTASVGWAVTDESYNIPKFNGKKMWGVRLFDDAKTAEERRTQRGSRRRLNR
  RKERINLLQDLFATEISKVDPNFFLRLDNSDLYREDKDEKLKSKYTLFNDKDFKDRDYHKKYPT
  IHHLIMDLIEDEGKKDIRLLYLACHYLLKNRGHFIFEGQKFDTKNSFDKSINDLKIHLRDEYNI
  DLEFNNEDLIEIITDTTLNKTNKKKELKNIVGDTKFLKAISAIMIGSSQKLVDLFEDGEFEETT
  VKSVDFSTTAFDDKYSEYEEALGDTISLLNILKSIYDSSILENLLKDADKSKDGNKYISKAFVK
  KFNKHGKDLKTLKRIIKKYLPSEYANIFRNKSINDNYVAYTKSNITSNKRTKASKFTKQEDFYK
  FIKKHLDTIKETKLNSSENEDLKLIDEMLTDIEFKTFIPKLKSSDNGVIPYQLKLMELKKILDN
  QSKYYDFLNESDEYGTVKDKVESIMEFRIPYYVGPLNPDSKYAWIKRENTKITPWNFKDIVDLD
  SSREEFIDRLIGRCTYLKEEKVLPKASLIYNEFMVLNELNNLKLNEFLITEEMKKAIFEELFKT
  KKKVTLKAVSNLLKKEFNLTGDILLSGTDGDFKQGLNSYIDFKNIIGDKVDRDDYRIKIEEIIK
  LIVLYEDDKTYLKKKIKSAYKNDFTDDEIKKIAALNYKDWGRLSKRFLTGIEGVDKTTGEKGSI
  IYFMREYNLNLMELMSGHYTFTEEVEKLNPVENRELCYEMVDELYLSPSVKRMLWQSLRVVDEI
  KRIIGKDPKKIFIEMARAKEAKNSRKESRKNKLLEFYKFGKKAFINEIGEERYNYLLNEINSEE
  ESKFRWDNLYLYYTQLGRCMYSLEPIDLADLKSNNIYDQDHIYPKSKIYDDSLENRVLVKKNLN
  HEKGNQYPIPEKVLNKNAYGFWKILFDKGLIGQKKYTRLTRRTPFEERELAEFIERQIVETRQA
  TKETANLLKNICQDSEIVYSKAENASRFRQEFDIIKCRTVNDLHHMHDAYLNIVVGNVYNTKFT
  KNPLNFIKDKDNVRSYNLENMFKYDVVRGSYTAWIADDSEGNVKAATIKKVKRELEGKNYRFTR
  MSYIGTGGLYDQNLMRKGKGQIPQKENTNKSNIEKYGGYNKASSAYFALIESDGKAGRERTLET
  IPIMVYNQEKYGNTEAVDKYLKDNLELQDPKILKDKIKINSLIKLDGFLYNIKGKTGDSLSIAG
  SVQLIVNKEEQKLIKKMDKFLVKKKDNKDIKVTSFDNIKEEELIKLYKTLSDKLNNGIYSNKRN
  NQAKNISEALDKFKEISIEEKIDVLNQIILLFQSYNNGCNLKSIGLSAKTGVVFIPKKLNYKEC
  KLINQSITGLFENEVDLLNL
  SEQ ID NO: 319
  MGKMYYLGLDIGTNSVGYAVTDPSYHLLKFKGEPMWGAHVFAAGNQSAERRSFRTSRRRLDRRQ
  QRVKLVQEIFAPVISPIDPRFFIRLHESALWRDDVAETDKHIFFNDPTYTDKEYYSDYPTIHHL
  IVDLMESSEKHDPRLVYLAVAWLVAHRGHFLNEVDKDNIGDVLSFDAFYPEFLAFLSDNGVSPW
  VCESKALQATLLSRNSVNDKYKALKSLIFGSQKPEDNFDANISEDGLIQLLAGKKVKVNKLFPQ
  ESNDASFTLNDKEDAIEEILGTLTPDECEWIAHIRRLFDWAIMKHALKDGRTISESKVKLYEQH
  HHDLTQLKYFVKTYLAKEYDDIFRNVDSETTKNYVAYSYHVKEVKGTLPKNKATQEEFCKYVLG
  KVKNIECSEADKVDFDEMIQRLTDNSFMPKQVSGENRVIPYQLYYYELKTILNKAASYLPFLTQ
  CGKDAISNQDKLLSIMTFRIPYFVGPLRKDNSEHAWLERKAGKIYPWNFNDKVDLDKSEEAFIR
  RMTNTCTYYPGEDVLPLDSLIYEKFMILNEINNIRIDGYPISVDVKQQVFGLFEKKRRVTVKDI
  QNLLLSLGALDKHGKLTGIDTTIHSNYNTYHHFKSLMERGVLTRDDVERIVERMTYSDDTKRVR
  LWLNNNYGTLTADDVKHISRLRKHDFGRLSKMFLTGLKGVHKETGERASILDFMWNTNDNLMQL
  LSECYTFSDEITKLQEAYYAKAQLSLNDFLDSMYISNAVKRPIYRTLAVVNDIRKACGTAPKRI
  FIEMARDGESKKKRSVTRREQIKNLYRSIRKDFQQEVDFLEKILENKSDGQLQSDALYLYFAQL
  GRDMYTGDPIKLEHIKDQSFYNIDHIYPQSMVKDDSLDNKVLVQSEINGEKSSRYPLDAAIRNK
  MKPLWDAYYNHGLISLKKYQRLTRSTPFTDDEKWDFINRQLVETRQSTKALAILLKRKFPDTEI
  VYSKAGLSSDFRHEFGLVKSRNINDLHHAKDAFLAIVTGNVYHERFNRRWEMVNQPYSVKTKTL
  FTHSIKNGNFVAWNGEEDLGRIVKMLKQNKNTIHFTRFSFDRKEGLFDIQPLKASTGLVPRKAG
  LDVVKYGGYDKSTAAYYLLVRFTLEDKKTQHKLMMIPVEGLYKARIDHDKEFLTDYAQTTISEI
  LQKDKQKVINIMFPMGTRHIKLNSMISIDGFYLSIGGKSSKGKSVLCHAMVPLIVPHKIECYIK
  AMESFARKFKENNKLRIVEKFDKITVEDNLNLYELFLQKLQHNPYNKFFSTQFDVLTNGRSTFT
  KLSPEEQVQTLLNILSIFKTCRSSGCDLKSINGSAQAARIMISADLTGLSKKYSDIRLVEQSAS
  GLFVSKSQNLLEYL
  SEQ ID NO: 320
  MTKKEQPYNIGLDIGTSSVGWAVTNDNYDLLNIKKKNLWGVRLFEEAQTAKETRLNRSTRRRYR
  RRKNRINWLNEIFSEELAKTDPSFLIRLQNSWVSKKDPDRKRDKYNLFIDGPYTDKEYYREFPT
  IFHLRKELILNKDKADIRLIYLALHNILKYRGNFTYEHQKFNISNLNNNLSKELIELNQQLIKY
  DISFPDDCDWNHISDILIGRGNATQKSSNILKDFTLDKETKKLLKEVINLILGNVAHLNTIFKT
  SLTKDEEKLNFSGKDIESKLDDLDSILDDDQFTVLDAANRIYSTITLNEILNGESYFSMAKVNQ
  YENHAIDLCKLRDMWHTTKNEEAVEQSRQAYDDYINKPKYGTKELYTSLKKFLKVALPTNLAKE
  AEEKISKGTYLVKPRNSENGVVPYQLNKIEMEKIIDNQSQYYPFLKENKEKLLSILSFRIPYYV
  GPLQSAEKNPFAWMERKSNGHARPWNFDEIVDREKSSNKFIRRMTVTDSYLVGEPVLPKNSLIY
  QRYEVLNELNNIRITENLKTNPIGSRLTVETKQRIYNELFKKYKKVTVKKLTKWLIAQGYYKNP
  ILIGLSQKDEFNSTLTTYLDMKKIFGSSFMEDNKNYDQIEELIEWLTIFEDKQILNEKLHSSKY
  SYTPDQIKKISNMRYKGWGRLSKKILMDITTETNTPQLLQLSNYSILDLMWATNNNFISIMSND
  KYDFKNYIENHNLNKNEDQNISDLVNDIHVSPALKRGITQSIKIVQEIVKFMGHAPKHIFIEVT
  RETKKSEITTSREKRIKRLQSKLLNKANDFKPQLREYLVPNKKIQEELKKHKNDLSSERIMLYF
  LQNGKSLYSEESLNINKLSDYQVDHILPRTYIPDDSLENKALVLAKENQRKADDLLLNSNVIDR
  NLERWTYMLNNNMIGLKKFKNLTRRVITDKDKLGFIHRQLVQTSQMVKGVANILDNMYKNQGTT
  CIQARANLSTAFRKALSGQDDTYHFKHPELVKNRNVNDFHHAQDAYLASFLGTYRLRRFPTNEM
  LLMNGEYNKFYGQVKELYSKKKKLPDSRKNGFIISPLVNGTTQYDRNTGEIIWNVGFRDKILKI
  FNYHQCNVTRKTEIKTGQFYDQTIYSPKNPKYKKLIAQKKDMDPNIYGGFSGDNKSSITIVKID
  NNKIKPVAIPIRLINDLKDKKTLQNWLEENVKHKKSIQIIKNNVPIGQIIYSKKVGLLSLNSDR
  EVANRQQLILPPEHSALLRLLQIPDEDLDQILAFYDKNILVEILQELITKMKKFYPFYKGEREF
  LIANIENFNQATTSEKVNSLEELITLLHANSTSAHLIFNNIEKKAFGRKTHGLTLNNTDFIYQS
  VTGLYETRIHIE
  SEQ ID NO: 321
  MTKFNKNYSIGLDIGVSSVGYAVVTEDYRVPAFKFKVLGNTEKEKIKKNLIGSTTFVSAQPAKG
  TRVFRVNRRRIDRRNHRITYLRDIFQKEIEKVDKNFYRRLDESFRVLGDKSEDLQIKQPFFGDK
  ELETAYHKKYPTIYHLRKHLADADKNSPVADIREVYMAISHILKYRGHFLTLDKINPNNINMQN
  SWIDFIESCQEVFDLEISDESKNIADIFKSSENRQEKVKKILPYFQQELLKKDKSIFKQLLQLL
  FGLKTKFKDCFELEEEPDLNFSKENYDENLENFLGSLEEDFSDVFAKLKVLRDTILLSGMLTYT
  GATHARFSATMVERYEEHRKDLQRFKFFIKQNLSEQDYLDIFGRKTQNGFDVDKETKGYVGYIT
  NKMVLTNPQKQKTIQQNFYDYISGKITGIEGAEYFLNKISDGTFLRKLRTSDNGAIPNQIHAYE
  LEKIIERQGKDYPFLLENKDKLLSILTFKIPYYVGPLAKGSNSRFAWIKRATSSDILDDNDEDT
  RNGKIRPWNYQKLINMDETRDAFITNLIGNDIILLNEKVLPKRSLIYEEVMLQNELTRVKYKDK
  YGKAHEFDSELRQNIINGLFKNNSKRVNAKSLIKYLSDNHKDLNAIEIVSGVEKGKSFNSTLKT
  YNDLKTIFSEELLDSEIYQKELEEIIKVITVFDDKKSIKNYLTKFFGHLEILDEEKINQLSKLR
  YSGWGRYSAKLLLDIRDEDTGFNLLQFLRNDEENRNLTKLISDNTLSFEPKIKDIQSKSTIEDD
  IFDEIKKLAGSPAIKRGILNSIKIVDELVQIIGYPPHNIVIEMARENMTTEEGQKKAKTRKTKL
  ESALKNIENSLLENGKVPHSDEQLQSEKLYLYYLQNGKDMYTLDKTGSPAPLYLDQLDQYEVDH
  IIPYSFLPIDSIDNKVLTHRENNQQKLNNIPDKETVANMKPFWEKLYNAKLISQTKYQRLTTSE
  RTPDGVLTESMKAGFIERQLVETRQIIKHVARILDNRFSDTKIITLKSQLITNFRNTFHIAKIR
  ELNDYHHAHDAYLAVVVGQTLLKVYPKLAPELIYGHHAHFNRHEENKATLRKHLYSNIMRFFNN
  PDSKVSKDIWDCNRDLPIIKDVIYNSQINFVKRTMIKKGAFYNQNPVGKFNKQLAANNRYPLKT
  KALCLDTSIYGGYGPMNSALSIIIIAERFNEKKGKIETVKEFHDIFIIDYEKFNNNPFQFLNDT
  SENGFLKKNNINRVLGFYRIPKYSLMQKIDGTRMLFESKSNLHKATQFKLTKTQNELFFHMKRL
  LTKSNLMDLKSKSAIKESQNFILKHKEEFDNISNQLSAFSQKMLGNTTSLKNLIKGYNERKIKE
  IDIRDETIKYFYDNFIKMFSFVKSGAPKDINDFFDNKCTVARMRPKPDKKLLNATLIHQSITGL
  YETRIDLSKLGED
  SEQ ID NO: 322
  MKQEYFLGLDMGTGSLGWAVTDSTYQVMRKHGKALWGTRLFESASTAEERRMFRTARRRLDRRN
  WRIQVLQEIFSEEISKVDPGFFLRMKESKYYPEDKRDAEGNCPELPYALFVDDNYTDKNYHKDY
  PTIYHLRKMLMETTEIPDIRLVYLVLHHMMKHRGHFLLSGDISQIKEFKSTFEQLIQNIQDEEL
  EWHISLDDAAIQFVEHVLKDRNLTRSTKKSRLIKQLNAKSACEKAILNLLSGGTVKLSDIFNNK
  ELDESERPKVSFADSGYDDYIGIVEAELAEQYYIIASAKAVYDWSVLVEILGNSVSISEAKIKV
  YQKHQADLKTLKKIVRQYMTKEDYKRVFVDTEEKLNNYSAYIGMTKKNGKKVDLKSKQCTQADF
  YDFLKKNVIKVIDHKEITQEIESEIEKENFLPKQVTKDNGVIPYQVHDYELKKILDNLGTRMPF
  IKENAEKIQQLFEFRIPYYVGPLNRVDDGKDGKFTWSVRKSDARIYPWNFTEVIDVEASAEKFI
  RRMTNKCTYLVGEDVLPKDSLVYSKFMVLNELNNLRLNGEKISVELKQRIYEELFCKYRKVTRK
  KLERYLVIEGIAKKGVEITGIDGDFKASLTAYHDFKERLTDVQLSQRAKEAIVLNVVLFGDDKK
  LLKQRLSKMYPNLTTGQLKGICSLSYQGWGRLSKTFLEEITVPAPGTGEVWNIMTALWQTNDNL
  MQLLSRNYGFTNEVEEFNTLKKETDLSYKTVDELYVSPAVKRQIWQTLKVVKEIQKVMGNAPKR
  VFVEMAREKQEGKRSDSRKKQLVELYRACKNEERDWITELNAQSDQQLRSDKLFLYYIQKGRCM
  YSGETIQLDELWDNTKYDIDHIYPQSKTMDDSLNNRVLVKKNYNAIKSDTYPLSLDIQKKMMSF
  WKMLQQQGFITKEKYVRLVRSDELSADELAGFIERQIVETRQSTKAVATILKEALPDTEIVYVK
  AGNVSNFRQTYELLKVREMNDLHHAKDAYLNIVVGNAYFVKFTKNAAWFIRNNPGRSYNLKRMF
  EEDIERSGEIAWKAGNKGSIVTVKKVMQKNNILVTRKAYEVKGGLFDQQIMKKGKGQVPIKGND
  ERLADIEKYGGYNKAAGTYFMLVKSLDKKGKEIRTIEFVPLYLKNQIEINHESAIQYLAQERGL
  NSPEILLSKIKIDTLFKVDGFKMWLSGRTGNQLIFKGANQLILSHQEAAILKGVVKYVNRKNEN
  KDAKLSERDGMTEEKLLQLYDTFLDKLSNTVYSIRLSAQIKTLTEKRAKFIGLSNEDQCIVLNE
  ILHMFQCQSGSANLKLIGGPGSAGILVMNNNITACKQISVINQSPTGIYEKEIDLIKL
  SEQ ID NO: 323
  MKKPYSIGLDIGTNSVGWAVVTDDYKVPAKKMKVLGNTDKSHIEKNLLGALLFDSGNTAEDRRL
  KRTARRRYTRRRNRILYLQEIFSEEMGKVDDSFFHRLEDSFLVTEDKRGERHPIFGNLEEEVKY
  HENFPTIYHLRQYLADNPEKVDLRLVYLALAHIIKFRGHFLIEGKFDTRNNDVQRLFQEFLAVY
  DNTFENSSLQEQNVQVEEILTDKISKSAKKDRVLKLFPNEKSNGRFAEFLKLIVGNQADFKKHF
  ELEEKAPLQFSKDTYEEELEVLLAQIGDNYAELFLSAKKLYDSILLSGILTVTDVGTKAPLSAS
  MIQRYNEHQMDLAQLKQFIRQKLSDKYNEVFSDVSKDGYAGYIDGKTNQEAFYKYLKGLLNKIE
  GSGYFLDKIEREDFLRKQRTFDNGSIPHQIHLQEMRAIIRRQAEFYPFLADNQDRIEKLLTFRI
  PYYVGPLARGKSDFAWLSRKSADKITPWNFDEIVDKESSAEAFINRMTNYDLYLPNQKVLPKHS
  LLYEKFTVYNELTKVKYKTEQGKTAFFDANMKQEIFDGVFKVYRKVTKDKLMDFLEKEFDEFRI
  VDLTGLDKENKVFNASYGTYHDLCKILDKDFLDNSKNEKILEDIVLTLTLFEDREMIRKRLENY
  SDLLTKEQVKKLERRHYTGWGRLSAELIHGIRNKESRKTILDYLIDDGNSNRNFMQLINDDALS
  FKEEIAKAQVIGETDNLNQVVSDIAGSPAIKKGILQSLKIVDELVKIMGHQPENIVVEMARENQ
  FTNQGRRNSQQRLKGLTDSIKEFGSQILKEHPVENSQLQNDRLFLYYLQNGRDMYTGEELDIDY
  LSQYDIDHIIPQAFIKDNSIDNRVLTSSKENRGKSDDVPSKDVVRKMKSYWSKLLSAKLITQRK
  FDNLTKAERGGLTDDDKAGFIKRQLVETRQITKHVARILDERFNTETDENNKKIRQVKIVTLKS
  NLVSNFRKEFELYKVREINDYHHAHDAYLNAVIGKALLGVYPQLEPEFVYGDYPHFHGHKENKA
  TAKKFFYSNIMNFFKKDDVRTDKNGEIIWKKDEHISNIKKVLSYPQVNIVKKVEEQTGGFSKES
  ILPKGNSDKLIPRKTKKFYWDTKKYGGFDSPIVAYSILVIADIEKGKSKKLKTVKALVGVTIME
  KMTFERDPVAFLERKGYRNVQEENIIKLPKYSLFKLENGRKRLLASARELQKGNEIVLPNHLGT
  LLYHAKNIHKVDEPKHLDYVDKHKDEFKELLDVVSNFSKKYTLAEGNLEKIKELYAQNNGEDLK
  ELASSFINLLTFTAIGAPATFKFFDKNIDRKRYTSTTEILNATLIHQSITGLYETRIDLNKLGG
  D
  SEQ ID NO: 324
  MDKKYSIGLDIGTNSVGWAVITDEYKVPSKKFKVLGNTDRHSIKKNLIGALLFDSGETAEATRL
  KRTARRRYTRRKNRICYLQEIFSNEMAKVDDSFFHRLEESFLVEEDKKHERHPIFGNIVDEVAY
  HEKYPTIYHLRKKLVDSTDKADLRLIYLALAHMIKFRGHFLIEGDLNPDNSDVDKLFIQLVQTY
  NQLFEENPINASGVDAKAILSARLSKSRRLENLIAQLPGEKKNGLFGNLIALSLGLTPNFKSNF
  DLAEDAKLQLSKDTYDDDLDNLLAQIGDQYADLFLAAKNLSDAILLSDILRVNTEITKAPLSAS
  MIKRYDEHHQDLTLLKALVRQQLPEKYKEIFFDQSKNGYAGYIDGGASQEEFYKFIKPILEKMD
  GTEELLVKLNREDLLRKQRTFDNGSIPHQIHLGELHAILRRQEDFYPFLKDNREKIEKILTFRI
  PYYVGPLARGNSRFAWMTRKSEETITPWNFEEVVDKGASAQSFIERMTNFDKNLPNEKVLPKHS
  LLYEYFTVYNELTKVKYVTEGMRKPAFLSGEQKKAIVDLLFKTNRKVTVKQLKEDYFKKIECFD
  SVEISGVEDRFNASLGTYHDLLKIIKDKDFLDNEENEDILEDIVLTLTLFEDREMIEERLKTYA
  HLFDDKVMKQLKRRRYTGWGRLSRKLINGIRDKQSGKTILDFLKSDGFANRNFMQLIHDDSLTF
  KEDIQKAQVSGQGDSLHEHIANLAGSPAIKKGILQTVKVVDELVKVMGRHKPENIVIEMARENQ
  TTQKGQKNSRERMKRIEEGIKELGSQILKEHPVENTQLQNEKLYLYYLQNGRDMYVDQELDINR
  LSDYDVDHIVPQSFLKDDSIDNKVLTRSDKNRGKSDNVPSEEVVKKMKNYWRQLLNAKLITQRK
  FDNLTKAERGGLSELDKAGFIKRQLVETRQITKHVAQILDSRMNTKYDENDKLIREVKVITLKS
  KLVSDFRKDFQFYKVREINNYHHAHDAYLNAVVGTALIKKYPKLESEFVYGDYKVYDVRKMIAK
  SEQEIGKATAKYFFYSNIMNFFKTEITLANGEIRKRPLIETNGETGEIVWDKGRDFATVRKVLS
  MPQVNIVKKTEVQTGGFSKESILPKRNSDKLIARKKDWDPKKYGGFDSPTVAYSVLVVAKVEKG
  KSKKLKSVKELLGITIMERSSFEKNPIDFLEAKGYKEVKKDLIIKLPKYSLFELENGRKRMLAS
  AGELQKGNELALPSKYVNFLYLASHYEKLKGSPEDNEQKQLFVEQHKHYLDEIIEQISEFSKRV
  ILADANLDKVLSAYNKHRDKPIREQAENIIHLFTLTNLGAPAAFKYFDTTIDRKRYTSTKEVLD
  ATLIHQSITGLYETRIDLSQLGGD
  SEQ ID NO: 325
  MTKPYSIGLDIGTNSVGWAVTTDNYKVPSKKMKVLGNTSKKYIKKNLLGVLLFDSGITAEGRRL
  KRTARRRYTRRRNRILYLQEIFSTEMATLDDAFFQRLDDSFLVPDDKRDSKYPIFGNLVEEKAY
  HDEFPTIYHLRKYLADSTKKADLRLVYLALAHMIKYRGHFLIEGEFNSKNNDIQKNFQDFLDTY
  NAIFESDLSLENSKQLEEIVKDKISKLEKKDRILKLFPGEKNSGIFSEFLKLIVGNQADFRKCF
  NLDEKASLHFSKESYDEDLETLLGYIGDDYSDVFLKAKKLYDAILLSGFLTVTDNETEAPLSSA
  MIKRYNEHKEDLALLKEYIRNISLKTYNEVFKDDTKNGYAGYIDGKTNQEDFYVYLKKLLAEFE
  GADYFLEKIDREDFLRKQRTFDNGSIPYQIHLQEMRAILDKQAKFYPFLAKNKERIEKILTFRI
  PYYVGPLARGNSDFAWSIRKRNEKITPWNFEDVIDKESSAEAFINRMTSFDLYLPEEKVLPKHS
  LLYETFNVYNELTKVRFIAESMRDYQFLDSKQKKDIVRLYFKDKRKVTDKDIIEYLHAIYGYDG
  IELKGIEKQFNSSLSTYHDLLNIINDKEFLDDSSNEAIIEEIIHTLTIFEDREMIKQRLSKFEN
  IFDKSVLKKLSRRHYTGWGKLSAKLINGIRDEKSGNTILDYLIDDGISNRNFMQLIHDDALSFK
  KKIQKAQIIGDEDKGNIKEVVKSLPGSPAIKKGILQSIKIVDELVKVMGGRKPESIVVEMAREN
  QYTNQGKSNSQQRLKRLEKSLKELGSKILKENIPAKLSKIDNNALQNDRLYLYYLQNGKDMYTG
  DDLDIDRLSNYDIDHIIPQAFLKDNSIDNKVLVSSASNRGKSDDVPSLEVVKKRKTFWYQLLKS
  KLISQRKFDNLTKAERGGLSPEDKAGFIQRQLVETRQITKHVARLLDEKFNNKKDENNRAVRTV
  KIITLKSTLVSQFRKDFELYKVREINDFHHAHDAYLNAVVASALLKKYPKLEPEFVYGDYPKYN
  SFRERKSATEKVYFYSNIMNIFKKSISLADGRVIERPLIEVNEETGESVWNKESDLATVRRVLS
  YPQVNVVKKVEEQNHGLDRGKPKGLFNANLSSKPKPNSNENLVGAKEYLDPKKYGGYAGISNSF
  TVLVKGTIEKGAKKKITNVLEFQGISILDRINYRKDKLNFLLEKGYKDIELIIELPKYSLFELS
  DGSRRMLASILSTNNKRGEIHKGNQIFLSQKFVKLLYHAKRISNTINENHRKYVENHKKEFEEL
  FYYILEFNENYVGAKKNGKLLNSAFQSWQNHSIDELCSSFIGPTGSERKGLFELTSRGSAADFE
  FLGVKIPRYRDYTPSSLLKDATLIHQSVTGLYETRIDLAKLGEG
  SEQ ID NO: 326
  MKKQKFSDYYLGFDIGTNSVGWCVTDLDYNVLRFNKKDMWGSRLFDEAKTAAERRVQRNSRRRL
  KRRKWRLNLLEEIFSDEIMKIDSNFFRRLKESSLWLEDKNSKEKFTLFNDDNYKDYDFYKQYPT
  IFHLRDELIKNPEKKDIRLIYLALHSIFKSRGHFLFEGQNLKEIKNFETLYNNLISFLEDNGIN
  KSIDKDNIEKLEKIICDSGKGLKDKEKEFKGIFNSDKQLVAIFKLSVGSSVSLNDLFDTDEYKK
  EEVEKEKISFREQIYEDDKPIYYSILGEKIELLDIAKSFYDFMVLNNILSDSNYISEAKVKLYE
  EHKKDLKNLKYIIRKYNKENYDKLFKDKNENNYPAYIGLNKEKDKKEVVEKSRLKIDDLIKVIK
  GYLPKPERIEEKDKTIFNEILNKIELKTILPKQRISDNGTLPYQIHEVELEKILENQSKYYDFL
  NYEENGVSTKDKLLKTFKFRIPYYVGPLNSYHKDKGGNSWIVRKEEGKILPWNFEQKVDIEKSA
  EEFIKRMTNKCTYLNGEDVIPKDSFLYSEYIILNELNKVQVNDEFLNEENKRKIIDELFKENKK
  VSEKKFKEYLLVNQIANRTVELKGIKDSFNSNYVSYIKFKDIFGEKLNLDIYKEISEKSILWKC
  LYGDDKKIFEKKIKNEYGDILNKDEIKKINSFKFNTWGRLSEKLLTGIEFINLETGECYSSVME
  ALRRTNYNLMELLSSKFTLQESIDNENKEMNEVSYRDLIEESYVSPSLKRAILQTLKIYEEIKK
  ITGRVPKKVFIEMARGGDESMKNKKIPARQEQLKKLYDSCGNDIANFSIDIKEMKNSLSSYDNN
  SLRQKKLYLYYLQFGKCMYTGREIDLDRLLQNNDTYDIDHIYPRSKVIKDDSFDNLVLVLKNEN
  AEKSNEYPVKKEIQEKMKSFWRFLKEKNFISDEKYKRLTGKDDFELRGFMARQLVNVRQTTKEV
  GKILQQIEPEIKIVYSKAEIASSFREMFDFIKVRELNDTHHAKDAYLNIVAGNVYNTKFTEKPY
  RYLQEIKENYDVKKIYNYDIKNAWDKENSLEIVKKNMEKNTVNITRFIKEEKGELFNLNPIKKG
  ETSNEIISIKPKLYDGKDNKLNEKYGYYTSLKAAYFIYVEHEKKNKKVKTFERITRIDSTLIKN
  EKNLIKYLVSQKKLLNPKIIKKIYKEQTLIIDSYPYTFTGVDSNKKVELKNKKQLYLEKKYEQI
  LKNALKFVEDNQGETEENYKFIYLKKRNNNEKNETIDAVKERYNIEFNEMYDKFLEKLSSKDYK
  NYINNKLYTNFLNSKEKFKKLKLWEKSLILREFLKIFNKNTYGKYEIKDSQTKEKLFSFPEDTG
  RIRLGQSSLGNNKELLEESVTGLFVKKIKL
  SEQ ID NO: 327
  MKNYTIGLDIGVASVGWVCIDENYKILNYNNRHAFGVHEEESAESAAGRRLKRGMRRRYNRRKK
  RLQLLQSLFDSYITDSGFFSKTDSQHFWKNNNEFENRSLTEVLSSLRISSRKYPTIYHLRSDLI
  ESNKKMDLRLVYLALHNLVKYRGHFLQEGNWSEAASAEGMDDQLLELVTRYAELENLSPLDLSE
  SQWKAAETLLLNRNLTKTDQSKELTAMFGKEYEPFCKLVAGLGVSLHQLFPSSEQALAYKETKT
  KVQLSNENVEEVMELLLEEESALLEAVQPFYQQVVLYELLKGETYVAKAKVSAFKQYQKDMASL
  KNLLDKTFGEKVYRSYFISDKNSQREYQKSHKVEVLCKLDQFNKEAKFAETFYKDLKKLLEDKS
  KTSIGTTEKDEMLRIIKAIDSNQFLQKQKGIQNAAIPHQNSLYEAEKILRNQQAHYPFITTEWI
  EKVKQILAFRIPYYIGPLVKDTTQSPFSWVERKGDAPITPWNFDEQIDKAASAEAFISRMRKTC
  TYLKGQEVLPKSSLTYERFEVLNELNGIQLRTTGAESDFRHRLSYEMKCWIIDNVFKQYKTVST
  KRLLQELKKSPYADELYDEHTGEIKEVFGTQKENAFATSLSGYISMKSILGAVVDDNPAMTEEL
  IYWIAVFEDREILHLKIQEKYPSITDVQRQKLALVKLPGWGRFSRLLIDGLPLDEQGQSVLDHM
  EQYSSVFMEVLKNKGFGLEKKIQKMNQHQVDGTKKIRYEDIEELAGSPALKRGIWRSVKIVEEL
  VSIFGEPANIVLEVAREDGEKKRTKSRKDQWEELTKTTLKNDPDLKSFIGEIKSQGDORFNEQR
  FWLYVTQQGKCLYTGKALDIQNLSMYEVDHILPQNFVKDDSLDNLALVMPEANQRKNQVGQNKM
  PLEIIEANQQYAMRTLWERLHELKLISSGKLGRLKKPSFDEVDKDKFIARQLVETRQIIKHVRD
  LLDERFSKSDIHLVKAGIVSKFRRFSEIPKIRDYNNKHHAMDALFAAALIQSILGKYGKNFLAF
  DLSKKDRQKQWRSVKGSNKEFFLFKNFGNLRLQSPVTGEEVSGVEYMKHVYFELPWQTTKMTQT
  GDGMFYKESIFSPKVKQAKYVSPKTEKFVHDEVKNHSICLVEFTFMKKEKEVQETKEIDLKVIE
  HHQFLKEPESQLAKFLAEKETNSPIIHARIIRTIPKYQKIWIEHFPYYFISTRELHNARQFEIS
  YELMEKVKQLSERSSVEELKIVFGLLIDQMNDNYPIYTKSSIQDRVQKFVDTQLYDFKSFEIGF
  EELKKAVAANAQRSDTFGSRISKKPKPEEVAIGYESITGLKYRKPRSVVGTKR
  SEQ ID NO: 328
  MKKEIKDYFLGLDVGTGSVGWAVTDTDYKLLKANRKDLWGMRCFETAETAEVRRLHRGARRRIE
  RRKKRIKLLQELFSQEIAKTDEGFFQRMKESPFYAEDKTILQENTLFNDKDFADKTYHKAYPTI
  NHLIKAWIENKVKPDPRLLYLACHNIIKKRGHFLFEGDFDSENQFDTSIQALFEYLREDMEVDI
  DADSQKVKEILKDSSLKNSEKQSRLNKILGLKPSDKQKKAITNLISGNKINFADLYDNPDLKDA
  EKNSISFSKDDFDALSDDLASILGDSFELLLKAKAVYNCSVLSKVIGDEQYLSFAKVKIYEKHK
  TDLTKLKNVIKKHFPKDYKKVFGYNKNEKNNNNYSGYVGVCKTKSKKLIINNSVNQEDFYKFLK
  TILSAKSEIKEVNDILTEIETGTFLPKQISKSNAEIPYQLRKMELEKILSNAEKHFSFLKQKDE
  KGLSHSEKIIMLLTFKIPYYIGPINDNHKKFFPDRCWVVKKEKSPSGKTTPWNFFDHIDKEKTA
  EAFITSRTNFCTYLVGESVLPKSSLLYSEYTVLNEINNLQIIIDGKNICDIKLKQKIYEDLFKK
  YKKITQKQISTFIKHEGICNKTDEVIILGIDKECTSSLKSYIELKNIFGKQVDEISTKNMLEEI
  IRWATIYDEGEGKTILKTKIKAEYGKYCSDEQIKKILNLKFSGWGRLSRKFLETVTSEMPGFSE
  PVNIITAMRETQNNLMELLSSEFTFTENIKKINSGFEDAEKQFSYDGLVKPLFLSPSVKKMLWQ
  TLKLVKEISHITQAPPKKIFIEMAKGAELEPARTKTRLKILQDLYNNCKNDADAFSSEIKDLSG
  KIENEDNLRLRSDKLYLYYTQLGKCMYCGKPIEIGHVFDTSNYDIDHIYPQSKIKDDSISNRVL
  VCSSCNKNKEDKYPLKSEIQSKQRGFWNFLQRNNFISLEKLNRLTRATPISDDETAKFIARQLV
  ETRQATKVAAKVLEKMFPETKIVYSKAETVSMFRNKFDIVKCREINDFHHAHDAYLNIVVGNVY
  NTKFTNNPWNFIKEKRDNPKIADTYNYYKVFDYDVKRNNITAWEKGKTIITVKDMLKRNTPIYT
  RQAACKKGELFNQTIMKKGLGQHPLKKEGPFSNISKYGGYNKVSAAYYTLIEYEEKGNKIRSLE
  TIPLYLVKDIQKDQDVLKSYLTDLLGKKEFKILVPKIKINSLLKINGFPCHITGKTNDSFLLRP
  AVQFCCSNNEVLYFKKIIRFSEIRSQREKIGKTISPYEDLSFRSYIKENLWKKTKNDEIGEKEF
  YDLLQKKNLEIYDMLLTKHKDTIYKKRPNSATIDILVKGKEKFKSLIIENQFEVILEILKLFSA
  TRNVSDLQHIGGSKYSGVAKIGNKISSLDNCILIYQSITGIFEKRIDLLKV
  SEQ ID NO: 329
  MEGQMKNNGNNLQQGNYYLGLDVGTSSVGWAVTDTDYNVLKFRGKSMWGARLFDEASTAEERRT
  HRGNRRRLARRKYRLLLLEQLFEKEIRKIDDNFFVRLHESNLWADDKSKPSKFLLFNDTNFTDK
  DYLKKYPTIYHLRSDLIHNSTEHDIRLVFLALHHLIKYRGHFIYDNSANGDVKTLDEAVSDFEE
  YLNENDIEFNIENKKEFINVLSDKHLTKKEKKISLKKLYGDITDSENINISVLIEMLSGSSISL
  SNLFKDIEFDGKQNLSLDSDIEETLNDVVDILGDNIDLLIHAKEVYDIAVLTSSLGKHKYLCDA
  KVELFEKNKKDLMILKKYIKKNHPEDYKKIFSSPTEKKNYAAYSQTNSKNVCSQEEFCLFIKPY
  IRDMVKSENEDEVRIAKEVEDKSFLTKLKGTNNSVVPYQIHERELNQILKNIVAYLPFMNDEQE
  DISVVDKIKLIFKFKIPYYVGPLNTKSTRSWVYRSDEKIYPWNFSNVIDLDKTAHEFMNRLIGR
  CTYTNDPVLPMDSLLYSKYNVLNEINPIKVNGKAIPVEVKQAIYTDLFENSKKKVTRKSIYIYL
  LKNGYIEKEDIVSGIDIEIKSKLKSHHDFTQIVQENKCTPEEIERIIKGILVYSDDKSMLRRWL
  KNNIKGLSENDVKYLAKLNYKEWGRLSKTLLTDIYTINPEDGEACSILDIMWNTNATLMEILSN
  EKYQFKQNIENYKAENYDEKQNLHEELDDMYISPAARRSIWQALRIVDEIVDIKKSAPKKIFIE
  MAREKKSAMKKKRTESRKDTLLELYKSCKSQADGFYDEELFEKLSNESNSRLRRDQLYLYYTOM
  GRSMYTGKRIDFDKLINDKNTYDIDHIYPRSKIKDDSITNRVLVEKDINGEKTDIYPISEDIRQ
  KMQPFWKILKEKGLINEEKYKRLTRNYELTDEELSSFVARQLVETQQSTKALATLLKKEYPSAK
  IVYSKAGNVSEFRNRKDKELPKFREINDLHHAKDAYLNIVVGNVYDTKFTEKFFNNIRNENYSL
  KRVFDFSVPGAWDAKGSTFNTIKKYMAKNNPIIAFAPYEVKGELFDQQIVPKGKGQFPIKQGKD
  IEKYGGYNKLSSAFLFAVEYKGKKARERSLETVYIKDVELYLQDPIKYCESVLGLKEPQIIKPK
  ILMGSLFSINNKKLVVTGRSGKQYVCHHIYQLSINDEDSQYLKNIAKYLQEEPDGNIERQNILN
  ITSVNNIKLFDVLCTKFNSNTYEIILNSLKNDVNEGREKFSELDILEQCNILLQLLKAFKCNRE
  SSNLEKLNNKKQAGVIVIPHLFTKCSVFKVIHQSITGLFEKEMDLLK
  SEQ ID NO: 330
  MGRKPYILSLDIGTGSVGYACMDKGFNVLKYHDKDALGVYLFDGALTAQERRQFRTSRRRKNRR
  IKRLGLLQELLAPLVQNPNFYQFQRQFAWKNDNMDFKNKSLSEVLSFLGYESKKYPTIYHLQEA
  LLLKDEKFDPELIYMALYHLVKYRGHFLFDHLKIENLTNNDNMHDFVELIETYENLNNIKLNLD
  YEKTKVIYEILKDNEMTKNDRAKRVKNMEKKLEQFSIMLLGLKFNEGKLFNHADNAEELKGANQ
  SHTFADNYEENLTPFLTVEQSEFIERANKIYLSLTLQDILKGKKSMAMSKVAAYDKFRNELKQV
  KDIVYKADSTRTQFKKIFVSSKKSLKQYDATPNDQTFSSLCLFDQYLIRPKKQYSLLIKELKKI
  IPQDSELYFEAENDTLLKVLNTTDNASIPMQINLYEAETILRNQQKYHAEITDEMIEKVLSLIQ
  FRIPYYVGPLVNDHTASKFGWMERKSNESIKPWNFDEVVDRSKSATQFIRRMTNKCSYLINEDV
  LPKNSLLYQEMEVLNELNATQIRLQTDPKNRKYRMMPQIKLFAVEHIFKKYKTVSHSKFLEIML
  NSNHRENFMNHGEKLSIFGTQDDKKFASKLSSYQDMTKIFGDIEGKRAQIEEIIQWITIFEDKK
  ILVQKLKECYPELTSKQINQLKKLNYSGWGRLSEKLLTHAYQGHSIIELLRHSDENFMEILTND
  VYGFQNFIKEENQVQSNKIQHQDIANLTTSPALKKGIWSTIKLVRELTSIFGEPEKIIMEFATE
  DQQKGKKQKSRKQLWDDNIKKNKLKSVDEYKYIIDVANKLNNEQLQQEKLWLYLSQNGKCMYSG
  QSIDLDALLSPNATKHYEVDHIFPRSFIKDDSIDNKVLVIKKMNQTKGDQVPLQFIQQPYERIA
  YWKSLNKAGLISDSKLHKLMKPEFTAMDKEGFIQRQLVETRQISVHVRDFLKEEYPNTKVIPMK
  AKMVSEFRKKFDIPKIRQMNDAHHAIDAYLNGVVYHGAQLAYPNVDLFDFNFKWEKVREKWKAL
  GEFNTKQKSRELFFFKKLEKMEVSQGERLISKIKLDMNHFKINYSRKLANIPQQFYNQTAVSPK
  TAELKYESNKSNEVVYKGLTPYQTYVVAIKSVNKKGKEKMEYQMIDHYVFDFYKFQNGNEKELA
  LYLAQRENKDEVLDAQIVYSLNKGDLLYINNHPCYFVSRKEVINAKQFELTVEQQLSLYNVMNN
  KETNVEKLLIEYDFIAEKVINEYHHYLNSKLKEKRVRTFFSESNQTHEDFIKALDELFKVVTAS
  ATRSDKIGSRKNSMTHRAFLGKGKDVKIAYTSISGLKTTKPKSLFKLAESRNEL
  SEQ ID NO: 331
  MAKILGLDLGTNSIGWAVVERENIDFSLIDKGVRIFSEGVKSEKGIESSRAAERTGYRSARKIK
  YRRKLRKYETLKVLSLNRMCPLSIEEVEEWKKSGFKDYPLNPEFLKWLSTDEESNVNPYFFRDR
  ASKHKVSLFELGRAFYHIAQRRGFLSNRLDQSAEGILEEHCPKIEAIVEDLISIDEISTNITDY
  FFETGILDSNEKNGYAKDLDEGDKKLVSLYKSLLAILKKNESDFENCKSEIIERLNKKDVLGKV
  KGKIKDISQAMLDGNYKTLGQYFYSLYSKEKIRNQYTSREEHYLSEFITICKVQGIDQINEEEK
  INEKKFDGLAKDLYKAIFFQRPLKSQKGLIGKCSFEKSKSRCAISHPDFEEYRMWTYLNTIKIG
  TQSDKKLRFLTQDEKLKLVPKFYRKNDFNFDVLAKELIEKGSSFGFYKSSKKNDFFYWFNYKPT
  DTVAACQVAASLKNAIGEDWKTKSFKYQTINSNKEQVSRTVDYKDLWHLLTVATSDVYLYEFAI
  DKLGLDEKNAKAFSKTKLKKDFASLSLSAINKILPYLKEGLLYSHAVFVANIENIVDENIWKDE
  KQRDYIKTQISEIIENYTLEKSRFEIINGLLKEYKSENEDGKRVYYSKEAEQSFENDLKKKLVL
  FYKSNEIENKEQQETIFNELLPIFIQQLKDYEFIKIQRLDQKVLIFLKGKNETGQIFCTEEKGT
  AEEKEKKIKNRLKKLYHPSDIEKFKKKIIKDEFGNEKIVLGSPLTPSIKNPMAMRALHQLRKVL
  NALILEGQIDEKTIIHIEMARELNDANKRKGIQDYQNDNKKFREDAIKEIKKLYFEDCKKEVEP
  TEDDILRYQLWMEQNRSEIYEEGKNISICDIIGSNPAYDIEHTIPRSRSQDNSQMNKTLCSQRF
  NREVKKQSMPIELNNHLEILPRIAHWKEEADNLTREIEIISRSIKAAATKEIKDKKIRRRHYLT
  LKRDYLQGKYDRFIWEEPKVGFKNSQIPDTGIITKYAQAYLKSYFKKVESVKGGMVAEFRKIWG
  IQESFIDENGMKHYKVKDRSKHTHHTIDAITIACMTKEKYDVLAHAWTLEDQQNKKEARSIIEA
  SKPWKTFKEDLLKIEEEILVSHYTPDNVKKQAKKIVRVRGKKQFVAEVERDVNGKAVPKKAASG
  KTIYKLDGEGKKLPRLQQGDTIRGSLHQDSIYGAIKNPLNTDEIKYVIRKDLESIKGSDVESIV
  DEVVKEKIKEAIANKVLLLSSNAQQKNKLVGTVWMNEEKRIAINKVRIYANSVKNPLHIKEHSL
  LSKSKHVHKQKVYGQNDENYAMAIYELDGKRDFELINIFNLAKLIKQGQGFYPLHKKKEIKGKI
  VFVPIEKRNKRDVVLKRGQQVVFYDKEVENPKDISEIVDFKGRIYIIEGLSIQRIVRPSGKVDE
  YGVIMLRYFKEARKADDIKQDNFKPDGVFKLGENKPTRKMNHQFTAFVEGIDFKVLPSGKFEKI
  SEQ ID NO: 332
  MEFKKVLGLDIGTNSIGCALLSLPKSIQDYGKGGRLEWLTSRVIPLDADYMKAFIDGKNGLPQV
  ITPAGKRRQKRGSRRLKHRYKLRRSRLIRVFKTLNWLPEDFPLDNPKRIKETISTEGKESERIS
  DYVPISDESYREFYREFGYPENEIEQVIEEINFRRKTKGKNKNPMIKLLPEDWVVYYLRKKALI
  KPTTKEELIRIIYLFNQRRGFKSSRKDLTETAILDYDEFAKRLAEKEKYSAENYETKFVSITKV
  KEVVELKTDGRKGKKRFKVILEDSRIEPYEIERKEKPDWEGKEYTFLVTQKLEKGKFKQNKPDL
  PKEEDWALCTTALDNRMGSKHPGEFFFDELLKAFKEKRGYKIRQYPVNRWRYKKELEFIWTKQC
  QLNPELNNLNINKEILRKLATVLYPSQSKFFGPKIKEFENSDVLHIISEDIIYYQRDLKSQKSL
  ISECRYEKRKGIDGEIYGLKCIPKSSPLYQEFRIWQDIHNIKVIRKESEVNGKKKINIDETQLY
  INENIKEKLFELFNSKDSLSEKDILELISLNIINSGIKISKKEEETTHRINLFANRKELKGNET
  KSRYRKVFKKLGFDGEYILNHPSKLNRLWHSDYSNDYADKEKTEKSILSSLGWKNRNGKWEKSK
  NYDVFNLPLEVAKAIANLPPLKKEYGSYSALAIRKMLVVMRDGKYWQHPDQIAKDQENTSLMLE
  DKNLIQLTNNQRKVLNKYLLTLAEVQKRSTLIKQKLNEIEHNPYKLELVSDQDLEKQVLKSFLE
  KKNESDYLKGLKTYQAGYLIYGKHSEKDVPIVNSPDELGEYIRKKLPNNSLRNPIVEQVIRETI
  FIVRDVWKSFGIIDEIHIELGRELKNNSEERKKTSESQEKNFQEKERARKLLKELLNSSNFEHY
  DENGNKIFSSFTVNPNPDSPLDIEKFRIWKNQSGLTDEELNKKLKDEKIPTEIEVKKYILWLTQ
  KCRSPYTGKIIPLSKLFDSNVYEIEHIIPRSKMKNDSTNNLVICELGVNKAKGDRLAANFISES
  NGKCKFGEVEYTLLKYGDYLQYCKDTFKYQKAKYKNLLATEPPEDFIERQINDTRYIGRKLAEL
  LTPVVKDSKNIIFTIGSITSELKITWGLNGVWKDILRPRFKRLESIINKKLIFQDEDDPNKYHF
  DLSINPQLDKEGLKRLDHRHHALDATIIAATTREHVRYLNSLNAADNDEEKREYFLSLCNHKIR
  DFKLPWENFTSEVKSKLLSCVVSYKESKPILSDPFNKYLKWEYKNGKWQKVFAIQIKNDRWKAV
  RRSMFKEPIGTVWIKKIKEVSLKEAIKIQAIWEEVKNDPVRKKKEKYIYDDYAQKVIAKIVQEL
  GLSSSMRKQDDEKLNKFINEAKVSAGVNKNLNTTNKTIYNLEGRFYEKIKVAEYVLYKAKRMPL
  NKKEYIEKLSLQKMFNDLPNFILEKSILDNYPEILKELESDNKYIIEPHKKNNPVNRLLLEHIL
  EYHNNPKEAFSTEGLEKLNKKAINKIGKPIKYITRLDGDINEEEIFRGAVFETDKGSNVYFVMY
  ENNQTKDREFLKPNPSISVLKAIEHKNKIDFFAPNRLGFSRIILSPGDLVYVPTNDQYVLIKDN
  SSNETIINWDDNEFISNRIYQVKKFTGNSCYFLKNDIASLILSYSASNGVGEFGSQNISEYSVD
  DPPIRIKDVCIKIRVDRLGNVRPL
  SEQ ID NO: 333
  MKHILGLDLGTNSIGWALIERNIEEKYGKIIGMGSRIVPMGAELSKFEQGQAQTKNADRRTNRG
  ARRLNKRYKQRRNKLIYILQKLDMLPSQIKLKEDFSDPNKIDKITILPISKKQEQLTAFDLVSL
  RVKALTEKVGLEDLGKIIYKYNQLRGYAGGSLEPEKEDIFDEEQSKDKKNKSFIAFSKIVFLGE
  PQEEIFKNKKLNRRAIIVETEEGNFEGSTFLENIKVGDSLELLINISASKSGDTITIKLPNKTN
  WRKKMENIENQLKEKSKEMGREFYISEFLLELLKENRWAKIRNNTILRARYESEFEAIWNEQVK
  HYPFLENLDKKTLIEIVSFIFPGEKESQKKYRELGLEKGLKYIIKNQVVFYQRELKDQSHLISD
  CRYEPNEKAIAKSHPVFQEYKVWEQINKLIVNTKIEAGTNRKGEKKYKYIDRPIPTALKEWIFE
  ELQNKKEITFSAIFKKLKAEFDLREGIDFLNGMSPKDKLKGNETKLQLQKSLGELWDVLGLDSI
  NRQIELWNILYNEKGNEYDLTSDRTSKVLEFINKYGNNIVDDNAEETAIRISKIKFARAYSSLS
  LKAVERILPLVRAGKYFNNDFSQQLQSKILKLLNENVEDPFAKAAQTYLDNNQSVLSEGGVGNS
  IATILVYDKHTAKEYSHDELYKSYKEINLLKQGDLRNPLVEQIINEALVLIRDIWKNYGIKPNE
  IRVELARDLKNSAKERATIHKRNKDNQTINNKIKETLVKNKKELSLANIEKVKLWEAQRHLSPY
  TGQPIPLSDLFDKEKYDVDHIIPISRYEDDSFTNKVISEKSVNQEKANRTAMEYFEVGSLKYSI
  FTKEQFIAHVNEYFSGVKRKNLLATSIPEDPVQRQIKDTQYIAIRVKEELNKIVGNENVKTTTG
  SITDYLRNHWGLTDKFKLLLKERYEALLESEKFLEAEYDNYKKDFDSRKKEYEEKEVLFEEQEL
  TREEFIKEYKENYIRYKKNKLIIKGWSKRIDHRHHAIDALIVACTEPAHIKRLNDLNKVLQDWL
  VEHKSEFMPNFEGSNSELLEEILSLPENERTEIFTQIEKFRAIEMPWKGFPEQVEQKLKEIIIS
  HKPKDKLLLQYNKAGDRQIKLRGQLHEGTLYGISQGKEAYRIPLTKFGGSKFATEKNIQKIVSP
  FLSGFIANHLKEYNNKKEEAFSAEGIMDLNNKLAQYRNEKGELKPHTPISTVKIYYKDPSKNKK
  KKDEEDLSLQKLDREKAFNEKLYVKTGDNYLFAVLEGEIKTKKTSQIKRLYDIISFFDATNFLK
  EEFRNAPDKKTFDKDLLFRQYFEERNKAKLLFTLKQGDFVYLPNENEEVILDKESPLYNQYWGD
  LKERGKNIYVVQKFSKKQIYFIKHTIADIIKKDVEFGSQNCYETVEGRSIKENCFKLEIDRLGN
  IVKVIKR
  SEQ ID NO: 334
  MHVEIDFPHFSRGDSHLAMNKNEILRGSSVLYRLGLDLGSNSLGWFVTHLEKRGDRHEPVALGP
  GGVRIFPDGRDPQSGTSNAVDRRMARGARKRRDRFVERRKELIAALIKYNLLPDDARERRALEV
  LDPYALRKTALTDTLPAHHVGRALFHLNQRRGFQSNRKTDSKQSEDGAIKQAASRLATDKGNET
  LGVFFADMHLRKSYEDRQTAIRAELVRLGKDHLTGNARKKIWAKVRKRLFGDEVLPRADAPHGV
  RARATITGTKASYDYYPTRDMLRDEFNAIWAGQSAHHATITDEARTEIEHIIFYQRPLKPAIVG
  KCTLDPATRPFKEDPEGYRAPWSHPLAQRFRILSEARNLEIRDTGKGSRRLTKEQSDLVVAALL
  ANREVKFDKLRTLLKLPAEARFNLESDRRAALDGDQTAARLSDKKGFNKAWRGFPPERQIAIVA
  RLEETEDENELIAWLEKECALDGAAAARVANTTLPDGHCRLGLRAIKKIVPIMQDGLDEDGVAG
  AGYHIAAKRAGYDHAKLPTGEQLGRLPYYGQWLQDAVVGSGDARDQKEKQYGQFPNPTVHIGLG
  QLRRVVNDLIDKYGPPTEISIEFTRALKLSEQQKAERQREQRRNQDKNKARAEELAKFGRPANP
  RNLLKMRLWEELAHDPLDRKCVYTGEQISIERLLSDEVDIDHILPVAMTLDDSPANKIICMRYA
  NRHKRKQTPSEAFGSSPTLQGHRYNWDDIAARATGLPRNKRWRFDANAREEFDKRGGFLARQLN
  ETGWLARLAKQYLGAVTDPNQIWVVPGRLTSMLRGKWGLNGLLPSDNYAGVQDKAEEFLASTDD
  MEFSGVKNRADHRHHAIDGLVTALTDRSLLWKMANAYDEEHEKFVIEPPWPTMRDDLKAALEKM
  VVSHKPDHGIEGKLHEDSAYGFVKPLDATGLKEEEAGNLVYRKAIESLNENEVDRIRDIQLRTI
  VRDHVNVEKTKGVALADALRQLQAPSDDYPQFKHGLRHVRILKKEKGDYLVPIANRASGVAYKA
  YSAGENFCVEVFETAGGKWDGEAVRRFDANKKNAGPKIAHAPQWRDANEGAKLVMRIHKGDLIR
  LDHEGRARIMVVHRLDAAAGRFKLADHNETGNLDKRHATNNDIDPFRWLMASYNTLKKLAAVPV
  RVDELGRVWRVMPN
  SEQ ID NO: 335
  METTLGIDLGTNSIGLALVDQEEHQILYSGVRIFPEGINKDTIGLGEKEESRNATRRAKRQMRR
  QYFRKKLRKAKLLELLIAYDMCPLKPEDVRRWKNWDKQQKSTVRQFPDTPAFREWLKQNPYELR
  KQAVTEDVTRPELGRILYQMIQRRGFLSSRKGKEEGKIFTGKDRMVGIDETRKNLQKQTLGAYL
  YDIAPKNGEKYRFRTERVRARYTLRDMYIREFEIIWQRQAGHLGLAHEQATRKKNIFLEGSATN
  VRNSKLITHLQAKYGRGHVLIEDTRITVTFQLPLKEVLGGKIEIEEEQLKFKSNESVLFWQRPL
  RSQKSLLSKCVFEGRNFYDPVHQKWIIAGPTPAPLSHPEFEEFRAYQFINNIIYGKNEHLTAIQ
  REAVFELMCTESKDFNFEKIPKHLKLFEKFNFDDTTKVPACTTISQLRKLFPHPVWEEKREEIW
  HCFYFYDDNTLLFEKLQKDYALQTNDLEKIKKIRLSESYGNVSLKAIRRINPYLKKGYAYSTAV
  LLGGIRNSFGKRFEYFKEYEPEIEKAVCRILKEKNAEGEVIRKIKDYLVHNRFGFAKNDRAFQK
  LYHHSQAITTQAQKERLPETGNLRNPIVQQGLNELRRTVNKLLATCREKYGPSFKFDHIHVEMG
  RELRSSKTEREKQSRQIRENEKKNEAAKVKLAEYGLKAYRDNIQKYLLYKEIEEKGGTVCCPYT
  GKTLNISHTLGSDNSVQIEHIIPYSISLDDSLANKTLCDATFNREKGELTPYDFYQKDPSPEKW
  GASSWEEIEDRAFRLLPYAKAQRFIRRKPQESNEFISRQLNDTRYISKKAVEYLSAICSDVKAF
  PGQLTAELRHLWGLNNILQSAPDITFPLPVSATENHREYYVITNEQNEVIRLFPKQGETPRTEK
  GELLLTGEVERKVFRCKGMQEFQTDVSDGKYWRRIKLSSSVTWSPLFAPKPISADGQIVLKGRI
  EKGVFVCNQLKQKLKTGLPDGSYWISLPVISQTFKEGESVNNSKLTSQQVQLFGRVREGIFRCH
  NYQCPASGADGNFWCTLDTDTAQPAFTPIKNAPPGVGGGQIILTGDVDDKGIFHADDDLHYELP
  ASLPKGKYYGIFTVESCDPTLIPIELSAPKTSKGENLIEGNIWVDEHTGEVRFDPKKNREDQRH
  HAIDAIVIALSSQSLFQRLSTYNARRENKKRGLDSTEHFPSPWPGFAQDVRQSVVPLLVSYKQN
  PKTLCKISKTLYKDGKKIHSCGNAVRGQLHKETVYGQRTAPGATEKSYHIRKDIRELKTSKHIG
  KVVDITIRQMLLKHLQENYHIDITQEFNIPSNAFFKEGVYRIFLPNKHGEPVPIKKIRMKEELG
  NAERLKDNINQYVNPRNNHHVMIYQDADGNLKEEIVSFWSVIERQNQGQPIYQLPREGRNIVSI
  LQINDTFLIGLKEEEPEVYRNDLSTLSKHLYRVQKLSGMYYTFRHHLASTLNNEREEFRIQSLE
  AWKRANPVKVQIDEIGRITFLNGPLC
  SEQ ID NO: 336
  MESSQILSPIGIDLGGKFTGVCLSHLEAFAELPNHANTKYSVILIDHNNFQLSQAQRRATRHRV
  RNKKRNQFVKRVALQLFQHILSRDLNAKEETALCHYLNNRGYTYVDTDLDEYIKDETTINLLKE
  LLPSESEHNFIDWFLQKMQSSEFRKILVSKVEEKKDDKELKNAVKNIKNFITGFEKNSVEGHRH
  RKVYFENIKSDITKDNQLDSIKKKIPSVCLSNLLGHLSNLQWKNLHRYLAKNPKQFDEQTFGNE
  FLRMLKNFRHLKGSQESLAVRNLIQQLEQSQDYISILEKTPPEITIPPYEARTNTGMEKDQSLL
  LNPEKLNNLYPNWRNLIPGIIDAHPFLEKDLEHTKLRDRKRIISPSKQDEKRDSYILQRYLDLN
  KKIDKFKIKKQLSFLGQGKQLPANLIETQKEMETHFNSSLVSVLIQIASAYNKEREDAAQGIWF
  DNAFSLCELSNINPPRKQKILPLLVGAILSEDFINNKDKWAKFKIFWNTHKIGRTSLKSKCKEI
  EEARKNSGNAFKIDYEEALNHPEHSNNKALIKIIQTIPDIIQAIQSHLGHNDSQALIYHNPFSL
  SQLYTILETKRDGFHKNCVAVTCENYWRSQKTEIDPEISYASRLPADSVRPFDGVLARMMQRLA
  YEIAMAKWEQIKHIPDNSSLLIPIYLEQNRFEFEESFKKIKGSSSDKTLEQAIEKQNIQWEEKF
  QRIINASMNICPYKGASIGGQGEIDHIYPRSLSKKHFGVIFNSEVNLIYCSSQGNREKKEEHYL
  LEHLSPLYLKHQFGTDNVSDIKNFISQNVANIKKYISFHLLTPEQQKAARHALFLDYDDEAFKT
  ITKFLMSQQKARVNGTQKFLGKQIMEFLSTLADSKQLQLEFSIKQITAEEVHDHRELLSKQEPK
  LVKSRQQSFPSHAIDATLTMSIGLKEFPQFSQELDNSWFINHLMPDEVHLNPVRSKEKYNKPNI
  SSTPLFKDSLYAERFIPVWVKGETFAIGFSEKDLFEIKPSNKEKLFTLLKTYSTKNPGESLQEL
  QAKSKAKWLYFPINKTLALEFLHHYFHKEIVTPDDTTVCHFINSLRYYTKKESITVKILKEPMP
  VLSVKFESSKKNVLGSFKHTIALPATKDWERLFNHPNFLALKANPAPNPKEFNEFIRKYFLSDN
  NPNSDIPNNGHNIKPQKHKAVRKVFSLPVIPGNAGTMMRIRRKDNKGQPLYQLQTIDDTPSMGI
  QINEDRLVKQEVLMDAYKTRNLSTIDGINNSEGQAYATFDNWLTLPVSTFKPEIIKLEMKPHSK
  TRRYIRITQSLADFIKTIDEALMIKPSDSIDDPLNMPNEIVCKNKLFGNELKPRDGKMKIVSTG
  KIVTYEFESDSTPQWIQTLYVTQLKKQP
  SEQ ID NO: 337
  MKKIVGLDLGTNSIGWALINAYINKEHLYGIEACGSRIIPMDAAILGNFDKGNSISQTADRTSY
  RGIRRLRERHLLRRERLHRILDLLGFLPKHYSDSLNRYGKFLNDIECKLPWVKDETGSYKFIFQ
  ESFKEMLANFTEHHPILIANNKKVPYDWTIYYLRKKALTQKISKEELAWILLNFNQKRGYYQLR
  GEEEETPNKLVEYYSLKVEKVEDSGERKGKDTWYNVHLENGMIYRRTSNIPLDWEGKTKEFIVT
  TDLEADGSPKKDKEGNIKRSFRAPKDDDWTLIKKKTEADIDKIKMTVGAYIYDTLLQKPDQKIR
  GKLVRTIERKYYKNELYQILKTQSEFHEELRDKQLYIACLNELYPNNEPRRNSISTRDFCHLFI
  EDIIFYQRPLKSKKSLIDNCPYEENRYIDKESGEIKHASIKCIAKSHPLYQEFRLWQFIVNLRI
  YRKETDVDVTQELLPTEADYVTLFEWLNEKKEIDQKAFFKYPPFGFKKTTSNYRWNYVEDKPYP
  CNETHAQIIARLGKAHIPKAFLSKEKEETLWHILYSIEDKQEIEKALHSFANKNNLSEEFIEQF
  KNEPPEKKEYGSYSAKAIKKLLPLMRMGKYWSIENIDNGTRIRINKIIDGEYDENIRERVRQKA
  INLTDITHFRALPLWLACYLVYDRHSEVKDIVKWKTPKDIDLYLKSFKQHSLRNPIVEQVITET
  LRTVRDIWQQVGHIDEIHIELGREMKNPADKRARMSQQMIKNENTNLRIKALLTEFLNPEFGIE
  NVRPYSPSQQDLLRIYEEGVLNSILELPEDIGIILGKFNQTDTLKRPTRSEILRYKLWLEQKYR
  SPYTGEMIPLSKLFTPAYEIEHIIPQSRYFDDSLSNKVICESEINKLKDRSLGYEFIKNHHGEK
  VELAFDKPVEVLSVEAYEKLVHESYSHNRSKMKKLLMEDIPDQFIERQLNDSRYISKVVKSLLS
  NIVREENEQEAISKNVIPCTGGITDRLKKDWGINDVWNKIVLPRFIRLNELTESTRFTSINTNN
  TMIPSMPLELQKGFNKKRIDHRHHAMDAIIIACANRNIVNYLNNVSASKNTKITRRDLQTLLCH
  KDKTDNNGNYKWVIDKPWETFTQDTLTALQKITVSFKQNLRVINKTTNHYQHYENGKKIVSNQS
  KGDSWAIRKSMHKETVHGEVNLRMIKTVSFNEALKKPQAIVEMDLKKKILAMLELGYDTKRIKN
  YFEENKDTWQDINPSKIKVYYFTKETKDRYFAVRKPIDTSFDKKKIKESITDTGIQQIMLRHLE
  TKDNDPTLAFSPDGIDEMNRNILILNKGKKHQPIYKVRVYEKAEKFTVGQKGNKRTKFVEAAKG
  TNLFFAIYETEEIDKDTKKVIRKRSYSTIPLNVVIERQKQGLSSAPEDENGNLPKYILSPNDLV
  YVPTQEEINKGEVVMPIDRDRIYKMVDSSGITANFIPASTANLIFALPKATAEIYCNGENCIQN
  EYGIGSPQSKNQKAITGEMVKEICFPIKVDRLGNIIQVGSCILTN
  SEQ ID NO: 338
  MSRSLTFSFDIGYASIGWAVIASASHDDADPSVCGCGTVLFPKDDCQAFKRREYRRLRRNIRSR
  RVRIERIGRLLVQAQIITPEMKETSGHPAPFYLASEALKGHRTLAPIELWHVLRWYAHNRGYDN
  NASWSNSLSEDGGNGEDTERVKHAQDLMDKHGTATMAETICRELKLEEGKADAPMEVSTPAYKN
  LNTAFPRLIVEKEVRRILELSAPLIPGLTAEIIELIAQHHPLTTEQRGVLLQHGIKLARRYRGS
  LLFGQLIPRFDNRIISRCPVTWAQVYEAELKKGNSEQSARERAEKLSKVPTANCPEFYEYRMAR
  ILCNIRADGEPLSAEIRRELMNQARQEGKLTKASLEKAISSRLGKETETNVSNYFTLHPDSEEA
  LYLNPAVEVLQRSGIGQILSPSVYRIAANRLRRGKSVTPNYLLNLLKSRGESGEALEKKIEKES
  KKKEADYADTPLKPKYATGRAPYARTVLKKVVEEILDGEDPTRPARGEAHPDGELKAHDGCLYC
  LLDTDSSVNQHQKERRLDTMTNNHLVRHRMLILDRLLKDLIQDFADGQKDRISRVCVEVGKELT
  TFSAMDSKKIQRELTLRQKSHTDAVNRLKRKLPGKALSANLIRKCRIAMDMNWTCPFTGATYGD
  HELENLELEHIVPHSFRQSNALSSLVLTWPGVNRMKGQRTGYDFVEQEQENPVPDKPNLHICSL
  NNYRELVEKLDDKKGHEDDRRRKKKRKALLMVRGLSHKHQSQNHEAMKEIGMTEGMMTQSSHLM
  KLACKSIKTSLPDAHIDMIPGAVTAEVRKAWDVFGVFKELCPEAADPDSGKILKENLRSLTHLH
  HALDACVLGLIPYIIPAHHNGLLRRVLAMRRIPEKLIPQVRPVANQRHYVLNDDGRMMLRDLSA
  SLKENIREQLMEQRVIQHVPADMGGALLKETMQRVLSVDGSGEDAMVSLSKKKDGKKEKNQVKA
  SKLVGVFPEGPSKLKALKAAIEIDGNYGVALDPKPVVIRHIKVFKRIMALKEQNGGKPVRILKK
  GMLIHLTSSKDPKHAGVWRIESIQDSKGGVKLDLQRAHCAVPKNKTHECNWREVDLISLLKKYQ
  MKRYPTSYTGTPR
  SEQ ID NO: 339
  MTQKVLGLDLGTNSIGSAVRNLDLSDDLQWQLEFFSSDIFRSSVNKESNGREYSLAAQRSAHRR
  SRGLNEVRRRRLWATLNLLIKHGFCPMSSESLMRWCTYDKRKGLFREYPIDDKDFNAWILLDFN
  GDGRPDYSSPYQLRRELVTRQFDFEQPIERYKLGRALYHIAQHRGFKSSKGETLSQQETNSKPS
  STDEIPDVAGAMKASEEKLSKGLSTYMKEHNLLTVGAAFAQLEDEGVRVRNNNDYRAIRSQFQH
  EIETIFKFQQGLSVESELYERLISEKKNVGTIFYKRPLRSQRGNVGKCTLERSKPRCAIGHPLF
  EKFRAWTLINNIKVRMSVDTLDEQLPMKLRLDLYNECFLAFVRTEFKFEDIRKYLEKRLGIHFS
  YNDKTINYKDSTSVAGCPITARFRKMLGEEWESFRVEGQKERQAHSKNNISFHRVSYSIEDIWH
  FCYDAEEPEAVLAFAQETLRLERKKAEELVRIWSAMPQGYAMLSQKAIRNINKILMLGLKYSDA
  VILAKVPELVDVSDEELLSIAKDYYLVEAQVNYDKRINSIVNGLIAKYKSVSEEYRFADHNYEY
  LLDESDEKDIIRQIENSLGARRWSLMDANEQTDILQKVRDRYQDFFRSHERKFVESPKLGESFE
  NYLTKKFPMVEREQWKKLYHPSQITIYRPVSVGKDRSVLRLGNPDIGAIKNPTVLRVLNTLRRR
  VNQLLDDGVISPDETRVVVETARELNDANRKWALDTYNRIRHDENEKIKKILEEFYPKRDGIST
  DDIDKARYVIDQREVDYFTGSKTYNKDIKKYKFWLEQGGQCMYTGRTINLSNLFDPNAFDIEHT
  IPESLSFDSSDMNLTLCDAHYNRFIKKNHIPTDMPNYDKAITIDGKEYPAITSQLQRWVERVER
  LNRNVEYWKGQARRAQNKDRKDQCMREMHLWKMELEYWKKKLERFTVTEVTDGFKNSQLVDTRV
  ITRHAVLYLKSIFPHVDVQRGDVTAKFRKILGIQSVDEKKDRSLHSHHAIDATTLTIIPVSAKR
  DRMLELFAKIEEINKMLSFSGSEDRTGLIQELEGLKNKLQMEVKVCRIGHNVSEIGTFINDNII
  VNHHIKNQALTPVRRRLRKKGYIVGGVDNPRWQTGDALRGEIHKASYYGAITQFAKDDEGKVLM
  KEGRPQVNPTIKFVIRRELKYKKSAADSGFASWDDLGKAIVDKELFALMKGQFPAETSFKDACE
  QGIYMIKKGKNGMPDIKLHHIRHVRCEAPQSGLKIKEQTYKSEKEYKRYFYAAVGDLYAMCCYT
  NGKIREFRIYSLYDVSCHRKSDIEDIPEFITDKKGNRLMLDYKLRTGDMILLYKDNPAELYDLD
  NVNLSRRLYKINRFESQSNLVLMTHHLSTSKERGRSLGKTVDYQNLPESIRSSVKSLNFLIMGE
  NRDFVIKNGKIIFNHR
  SEQ ID NO: 340
  MLVSPISVDLGGKNTGFFSFTDSLDNSQSGTVIYDESFVLSQVGRRSKRHSKRNNLRNKLVKRL
  FLLILQEHHGLSIDVLPDEIRGLFNKRGYTYAGFELDEKKKDALESDTLKEFLSEKLQSIDRDS
  DVEDFLNQIASNAESFKDYKKGFEAVFASATHSPNKKLELKDELKSEYGENAKELLAGLRVTKE
  ILDEFDKQENQGNLPRAKYFEELGEYIATNEKVKSFFDSNSLKLTDMTKLIGNISNYQLKELRR
  YFNDKEMEKGDIWIPNKLHKITERFVRSWHPKNDADRQRRAELMKDLKSKEIMELLTTTEPVMT
  IPPYDDMNNRGAVKCQTLRLNEEYLDKHLPNWRDIAKRLNHGKFNDDLADSTVKGYSEDSTLLH
  RLLDTSKEIDIYELRGKKPNELLVKTLGQSDANRLYGFAQNYYELIRQKVRAGIWVPVKNKDDS
  LNLEDNSNMLKRCNHNPPHKKNQIHNLVAGILGVKLDEAKFAEFEKELWSAKVGNKKLSAYCKN
  IEELRKTHGNTFKIDIEELRKKDPAELSKEEKAKLRLTDDVILNEWSQKIANFFDIDDKHRQRF
  NNLFSMAQLHTVIDTPRSGFSSTCKRCTAENRFRSETAFYNDETGEFHKKATATCQRLPADTQR
  PFSGKIERYIDKLGYELAKIKAKELEGMEAKEIKVPIILEQNAFEYEESLRKSKTGSNDRVINS
  KKDRDGKKLAKAKENAEDRLKDKDKRIKAFSSGICPYCGDTIGDDGEIDHILPRSHTLKIYGTV
  FNPEGNLIYVHQKCNQAKADSIYKLSDIKAGVSAQWIEEQVANIKGYKTFSVLSAEQQKAFRYA
  LFLQNDNEAYKKVVDWLRTDQSARVNGTQKYLAKKIQEKLTKMLPNKHLSFEFILADATEVSEL
  RRQYARQNPLLAKAEKQAPSSHAIDAVMAFVARYQKVFKDGTPPNADEVAKLAMLDSWNPASNE
  PLTKGLSTNQKIEKMIKSGDYGQKNMREVFGKSIFGENAIGERYKPIVVQEGGYYIGYPATVKK
  GYELKNCKVVTSKNDIAKLEKIIKNQDLISLKENQYIKIFSINKQTISELSNRYFNMNYKNLVE
  RDKEIVGLLEFIVENCRYYTKKVDVKFAPKYIHETKYPFYDDWRRFDEAWRYLQENQNKTSSKD
  RFVIDKSSLNEYYQPDKNEYKLDVDTQPIWDDFCRWYFLDRYKTANDKKSIRIKARKTFSLLAE
  SGVQGKVFRAKRKIPTGYAYQALPMDNNVIAGDYANILLEANSKTLSLVPKSGISIEKQLDKKL
  DVIKKTDVRGLAIDNNSFFNADFDTHGIRLIVENTSVKVGNFPISAIDKSAKRMIFRALFEKEK
  GKRKKKTTISFKESGPVQDYLKVFLKKIVKIQLRTDGSISNIVVRKNAADFTLSFRSEHIQKLL
  K
  SEQ ID NO: 341
  MAYRLGLDIGITSVGWAVVALEKDESGLKPVRIQDLGVRIFDKAEDSKTGASLALPRREARSAR
  RRTRRRRHRLWRVKRLLEQHGILSMEQIEALYAQRTSSPDVYALRVAGLDRCLIAEEIARVLIH
  IAHRRGFQSNRKSEIKDSDAGKLLKAVQENENLMQSKGYRTVAEMLVSEATKTDAEGKLVHGKK
  HGYVSNVRNKAGEYRHTVSRQAIVDEVRKIFAAQRALGNDVMSEELEDSYLKILCSQRNFDDGP
  GGDSPYGHGSVSPDGVRQSIYERMVGSCTFETGEKRAPRSSYSFERFQLLTKVVNLRIYRQQED
  GGRYPCELTQTERARVIDCAYEQTKITYGKLRKLLDMKDTESFAGLTYGLNRSRNKTEDTVFVE
  MKFYHEVRKALQRAGVFIQDLSIETLDQIGWILSVWKSDDNRRKKLSTLGLSDNVIEELLPLNG
  SKFGHLSLKAIRKILPFLEDGYSYDVACELAGYQFQGKTEYVKQRLLPPLGEGEVTNPVVRRAL
  SQAIKVVNAVIRKHGSPESIHIELARELSKNLDERRKIEKAQKENQKNNEQIKDEIREILGSAH
  VTGRDIVKYKLFKQQQEFCMYSGEKLDVTRLFEPGYAEVDHIIPYGISFDDSYDNKVLVKTEQN
  RQKGNRTPLEYLRDKPEQKAKFIALVESIPLSQKKKNHLLMDKRAIDLEQEGFRERNLSDTRYI
  TRALMNHIQAWLLFDETASTRSKRVVCVNGAVTAYMRARWGLTKDRDAGDKHHAADAVVVACIG
  DSLIQRVTKYDKFKRNALADRNRYVQQVSKSEGITQYVDKETGEVFTWESFDERKFLPNEPLEP
  WPFFRDELLARLSDDPSKNIRAIGLLTYSETEQIDPIFVSRMPTRKVTGAAHKETIRSPRIVKV
  DDNKGTEIQVVVSKVALTELKLTKDGEIKDYFRPEDDPRLYNTLRERLVQFGGDAKAAFKEPVY
  KISKDGSVRTPVRKVKIQEKLTLGVPVHGGRGIAENGGMVRIDVFAKGGKYYFVPIYVADVLKR
  ELPNRLATAHKPYSEWRVVDDSYQFKFSLYPNDAVMIKPSREVDITYKDRKEPVGCRIMYFVSA
  NIASASISLRTHDNSGELEGLGIQGLEVFEKYVVGPLGDTHPVYKERRMPFRVERKMN
  SEQ ID NO: 342
  MPVLSPLSPNAAQGRRRWSLALDIGEGSIGWAVAEVDAEGRVLQLTGTGVTLFPSAWSNENGTY
  VAHGAADRAVRGQQQRHDSRRRRLAGLARLCAPVLERSPEDLKDLTRTPPKADPRAIFFLRADA
  ARRPLDGPELFRVLHHMAAHRGIRLAELQEVDPPPESDADDAAPAATEDEDGTRRAAADERAFR
  RLMAEHMHRHGTQPTCGEIMAGRLRETPAGAQPVTRARDGLRVGGGVAVPTRALIEQEFDAIRA
  IQAPRHPDLPWDSLRRLVLDQAPIAVPPATPCLFLEELRRRGETFQGRTITREAIDRGLTVDPL
  IQALRIRETVGNLRLHERITEPDGRQRYVPRAMPELGLSHGELTAPERDTLVRALMHDPDGLAA
  KDGRIPYTRLRKLIGYDNSPVCFAQERDTSGGGITVNPTDPLMARWIDGWVDLPLKARSLYVRD
  VVARGADSAALARLLAEGAHGVPPVAAAAVPAATAAILESDIMQPGRYSVCPWAAEAILDAWAN
  APTEGFYDVTRGLFGFAPGEIVLEDLRRARGALLAHLPRTMAAARTPNRAAQQRGPLPAYESVI
  PSQLITSLRRAHKGRAADWSAADPEERNPFLRTWTGNAATDHILNQVRKTANEVITKYGNRRGW
  DPLPSRITVELAREAKHGVIRRNEIAKENRENEGRRKKESAALDTFCQDNTVSWQAGGLPKERA
  ALRLRLAQRQEFFCPYCAERPKLRATDLFSPAETEIDHVIERRMGGDGPDNLVLAHKDCNNAKG
  KKTPHEHAGDLLDSPALAALWQGWRKENADRLKGKGHKARTPREDKDFMDRVGWRFEEDARAKA
  EENQERRGRRMLHDTARATRLARLYLAAAVMPEDPAEIGAPPVETPPSPEDPTGYTAIYRTISR
  VQPVNGSVTHMLRQRLLQRDKNRDYQTHHAEDACLLLLAGPAVVQAFNTEAAQHGADAPDDRPV
  DLMPTSDAYHQQRRARALGRVPLATVDAALADIVMPESDRQDPETGRVHWRLTRAGRGLKRRID
  DLTRNCVILSRPRRPSETGTPGALHNATHYGRREITVDGRTDTVVTQRMNARDLVALLDNAKIV
  PAARLDAAAPGDTILKEIGTEIADRHDRVVDPEGTHARRWISARLAALVPAHAEAVARDIAELA
  DLDALADADRTPEQEARRSALRQSPYLGRAISAKKADGRARAREQEILTRALLDPHWGPRGLRH
  LIMREARAPSLVRIRANKTDAFGRPVPDAAVWVKTDGNAVSQLWRLTSVVTDDGRRIPLPKPIE
  KRIEISNLEYARLNGLDEGAGVTGNNAPPRPLRQDIDRLTPLWRDHGTAPGGYLGTAVGELEDK
  ARSALRGKAMRQTLTDAGITAEAGWRLDSEGAVCDLEVAKGDTVKKDGKTYKVGVITQGIFGMP
  VDAAGSAPRTPEDCEKFEEQYGIKPWKAKGIPLA
  SEQ ID NO: 343
  MNYTEKEKLFMKYILALDIGIASVGWAILDKESETVIEAGSNIFPEASAADNQLRRDMRGAKRN
  NRRLKTRINDFIKLWENNNLSIPQFKSTEIVGLKVRAITEEITLDELYLILYSYLKHRGISYLE
  DALDDTVSGSSAYANGLKLNAKELETHYPCEIQQERLNTIGKYRGQSQIINENGEVLDLSNVFT
  IGAYRKEIQRVFEIQKKYHPELTDEFCDGYMLIFNRKRKYYEGPGNEKSRTDYGRFTTKLDANG
  NYITEDNIFEKLIGKCSVYPDELRAAAASYTAQEYNVLNDLNNLTINGRKLEENEKHEIVERIK
  SSNTINMRKIISDCMGENIDDFAGARIDKSGKEIFHKFEVYNKMRKALLEIGIDISNYSREELD
  EIGYIMTINTDKEAMMEAFQKSWIDLSDDVKQCLINMRKTNGALFNKWQSFSLKIMNELIPEMY
  AQPKEQMTLLTEMGVTKGTQEEFAGLKYIPVDVVSEDIFNPVVRRSVRISFKILNAVLKKYKAL
  DTIVIEMPRDRNSEEQKKRINDSQKLNEKEMEYIEKKLAVTYGIKLSPSDFSSQKQLSLKLKLW
  NEQDGICLYSGKTIDPNDIINNPQLFEIDHIIPRSISFDDARSNKVLVYRSENQKKGNQTPYYY
  LTHSHSEWSFEQYKATVMNLSKKKEYAISRKKIQNLLYSEDITKMDVLKGFINRNINDTSYASR
  LVLNTIQNFFMANEADTKVKVIKGSYTHQMRCNLKLDKNRDESYSHHAVDAMLIGYSELGYEAY
  HKLQGEFIDFETGEILRKDMWDENMSDEVYADYLYGKKWANIRNEVVKAEKNVKYWHYVMRKSN
  RGLCNQTIRGTREYDGKQYKINKLDIRTKEGIKVFAKLAFSKKDSDRERLLVYLNDRRTFDDLC
  KIYEDYSDAANPFVQYEKETGDIIRKYSKKHNGPRIDKLKYKDGEVGACIDISHKYGFEKGSKK
  VILESLVPYRMDVYYKEENHSYYLVGVKQSDIKFEKGRNVIDEEAYARILVNEKMIQPGQSRAD
  LENLGFKFKLSFYKNDIIEYEKDGKIYTERLVSRTMPKQRNYIETKPIDKAKFEKQNLVGLGKT
  KFIKKYRYDILGNKYSCSEEKFTSFC
  SEQ ID NO: 344
  MLRLYCANNLVLNNVQNLWKYLLLLIFDKKIIFLFKIKVILIRRYMENNNKEKIVIGFDLGVAS
  VGWSIVNAETKEVIDLGVRLFSEPEKADYRRAKRTTRRLLRRKKFKREKFHKLILKNAEIFGLQ
  SRNEILNVYKDQSSKYRNILKLKINALKEEIKPSELVWILRDYLQNRGYFYKNEKLTDEFVSNS
  FPSKKLHEHYEKYGFFRGSVKLDNKLDNKKDKAKEKDEEEESDAKKESEELIFSNKQWINEIVK
  VFENQSYLTESFKEEYLKLFNYVRPFNKGPGSKNSRTAYGVFSTDIDPETNKFKDYSNIWDKTI
  GKCSLFEEEIRAPKNLPSALIFNLQNEICTIKNEFTEFKNWWLNAEQKSEILKFVFTELFNWKD
  KKYSDKKFNKNLQDKIKKYLLNFALENFNLNEEILKNRDLENDTVLGLKGVKYYEKSNATADAA
  LEFSSLKPLYVFIKFLKEKKLDLNYLLGLENTEILYFLDSIYLAISYSSDLKERNEWFKKLLKE
  LYPKIKNNNLEIIENVEDIFEITDQEKFESFSKTHSLSREAFNHIIPLLLSNNEGKNYESLKHS
  NEELKKRTEKAELKAQQNQKYLKDNFLKEALVPLSVKTSVLQAIKIFNQIIKNFGKKYEISQVV
  IEMARELTKPNLEKLLNNATNSNIKILKEKLDQTEKFDDFTKKKFIDKIENSVVFRNKLFLWFE
  QDRKDPYTQLDIKINEIEDETEIDHVIPYSKSADDSWFNKLLVKKSTNQLKKNKTVWEYYQNES
  DPEAKWNKFVAWAKRIYLVQKSDKESKDNSEKNSIFKNKKPNLKFKNITKKLFDPYKDLGFLAR
  NLNDTRYATKVFRDQLNNYSKHHSKDDENKLFKVVCMNGSITSFLRKSMWRKNEEQVYRFNFWK
  KDRDQFFHHAVDASIIAIFSLLTKTLYNKLRVYESYDVQRREDGVYLINKETGEVKKADKDYWK
  DQHNFLKIRENAIEIKNVLNNVDFQNQVRYSRKANTKLNTQLFNETLYGVKEFENNFYKLEKVN
  LFSRKDLRKFILEDLNEESEKNKKNENGSRKRILTEKYIVDEILQILENEEFKDSKSDINALNK
  YMDSLPSKFSEFFSQDFINKCKKENSLILTFDAIKHNDPKKVIKIKNLKFFREDATLKNKQAVH
  KDSKNQIKSFYESYKCVGFIWLKNKNDLEESIFVPINSRVIHFGDKDKDIFDEDSYNKEKLLNE
  INLKRPENKKFNSINEIEFVKFVKPGALLLNFENQQIYYISTLESSSLRAKIKLLNKMDKGKAV
  SMKKITNPDEYKIIEHVNPLGINLNWTKKLENNN
  SEQ ID NO: 345
  MLMSKHVLGLDLGVGSIGWCLIALDAQGDPAEILGMGSRVVPLNNATKAIEAFNAGAAFTASQE
  RTARRTMRRGFARYQLRRYRLRRELEKVGMLPDAALIQLPLLELWELRERAATAGRRLTLPELG
  RVLCHINQKRGYRHVKSDAAAIVGDEGEKKKDSNSAYLAGIRANDEKLQAEHKTVGQYFAEQLR
  QNQSESPTGGISYRIKDQIFSRQCYIDEYDQIMAVQRVHYPDILTDEFIRMLRDEVIEMQRPLK
  SCKHLVSLCEFEKQERVMRVQQDDGKGGWQLVERRVKFGPKVAPKSSPLFQLCCIYEAVNNIRL
  TRPNGSPCDITPEERAKIVAHLQSSASLSFAALKKLLKEKALIADQLTSKSGLKGNSTRVALAS
  ALQPYPQYHHLLDMELETRMMTVQLTDEETGEVTEREVAVVTDSYVRKPLYRLWHILYSIEERE
  AMRRALITQLGMKEEDLDGGLLDQLYRLDFVKPGYGNKSAKFICKLLPQLQQGLGYSEACAAVG
  YRHSNSPTSEEITERTLLEKIPLLQRNELRQPLVEKILNQMINLVNALKAEYGIDEVRVELARE
  LKMSREERERMARNNKDREERNKGVAAKIRECGLYPTKPRIQKYMLWKEAGRQCLYCGRSIEEE
  QCLREGGMEVEHIIPKSVLYDDSYGNKTCACRRCNKEKGNRTALEYIRAKGREAEYMKRINDLL
  KEKKISYSKHQRLRWLKEDIPSDFLERQLRLTQYISRQAMAILQQGIRRVSASEGGVTARLRSL
  WGYGKILHTLNLDRYDSMGETERVSREGEATEELHITNWSKRMDHRHHAIDALVVACTRQSYIQ
  RLNRLSSEFGREDKKKEDQEAQEQQATETGRLSNLERWLTQRPHFSVRTVSDKVAEILISYRPG
  QRVVTRGRNIYRKKMADGREVSCVQRGVLVPRGELMEASFYGKILSQGRVRIVKRYPLHDLKGE
  VVDPHLRELITTYNQELKSREKGAPIPPLCLDKDKKQEVRSVRCYAKTLSLDKAIPMCFDEKGE
  PTAFVKSASNHHLALYRTPKGKLVESIVTFWDAVDRARYGIPLVITHPREVMEQVLQRGDIPEQ
  VLSLLPPSDWVFVDSLQQDEMVVIGLSDEELQRALEAQNYRKISEHLYRVQKMSSSYYVFRYHL
  ETSVADDKNTSGRIPKFHRVQSLKAYEERNIRKVRVDLLGRISLL
  SEQ ID NO: 346
  MSDLVLGLDIGIGSVGVGILNKVTGEIIHKNSRIFPAAQAENNLVRRTNRQGRRLARRKKHRRV
  RLNRLFEESGLITDFTKISINLNPYQLRVKGLTDELSNEELFIALKNMVKHRGISYLDDASDDG
  NSSVGDYAQIVKENSKQLETKTPGQIQLERYQTYGQLRGDFTVEKDGKKHRLINVFPTSAYRSE
  ALRILQTQQEFNPQITDEFINRYLEILTGKRKYYHGPGNEKSRTDYGRYRTSGETLDNIFGILI
  GKCTFYPDEFRAAKASYTAQEFNLLNDLNNLTVPTETKKLSKEQKNQIINYVKNEKAMGPAKLF
  KYIAKLLSCDVADIKGYRIDKSGKAEIHTFEAYRKMKTLETLDIEQMDRETLDKLAYVLTLNTE
  REGIQEALEHEFADGSFSQKQVDELVQFRKANSSIFGKGWHNFSVKLMMELIPELYETSEEQMT
  ILTRLGKQKTTSSSNKTKYIDEKLLTEEIYNPVVAKSVRQAIKIVNAAIKEYGDFDNIVIEMAR
  ETNEDDEKKAIQKIQKANKDEKDAAMLKAANQYNGKAELPHSVFHGHKQLATKIRLWHQQGERC
  LYTGKTISIHDLINNSNQFEVDHILPLSITFDDSLANKVLVYATANQEKGQRTPYQALDSMDDA
  WSFRELKAFVRESKTLSNKKKEYLLTEEDISKFDVRKKFIERNLVDTRYASRVVLNALQEHFRA
  HKIDTKVSVVRGQFTSQLRRHWGIEKTRDTYHHHAVDALIIAASSQLNLWKKQKNTLVSYSEDQ
  LLDIETGELISDDEYKESVFKAPYQHFVDTLKSKEFEDSILFSYQVDSKFNRKISDATIYATRQ
  AKVGKDKADETYVLGKIKDIYTQDGYDAFMKIYKKDKSKFLMYRHDPQTFEKVIEPILENYPNK
  QINEKGKEVPCNPFLKYKEEHGYIRKYSKKGNGPEIKSLKYYDSKLGNHIDITPKDSNNKVVLQ
  SVSPWRADVYFNKTTGKYEILGLKYADLQFEKGTGTYKISQEKYNDIKKKEGVDSDSEFKFTLY
  KNDLLLVKDTETKEQQLFRFLSRTMPKQKHYVELKPYDKQKFEGGEALIKVLGNVANSGQCKKG
  LGKSNISIYKVRTDVLGNQHIIKNEGDKPKLDF
  SEQ ID NO: 347
  MNAEHGKEGLLIMEENFQYRIGLDIGITSVGWAVLQNNSQDEPVRITDLGVRIFDVAENPKNGD
  ALAAPRRDARTTRRRLRRRRHRLERIKFLLQENGLIEMDSFMERYYKGNLPDVYQLRYEGLDRK
  LKDEELAQVLIHIAKHRGFRSTRKAETKEKEGGAVLKATTENQKIMQEKGYRTVGEMLYLDEAF
  HTECLWNEKGYVLTPRNRPDDYKHTILRSMLVEEVHAIFAAQRAHGNQKATEGLEEAYVEIMTS
  QRSFDMGPGLQPDGKPSPYAMEGFGDRVGKCTFEKDEYRAPKATYTAELFVALQKINHTKLIDE
  FGTGRFFSEEERKTIIGLLLSSKELKYGTIRKKLNIDPSLKFNSLNYSAKKEGETEEERVLDTE
  KAKFASMFWTYEYSKCLKDRTEEMPVGEKADLFDRIGEILTAYKNDDSRSSRLKELGLSGEEID
  GLLDLSPAKYQRVSLKAMRKMQPYLEDGLIYDKACEAAGYDFRALNDGNKKHLLKGEEINAIVN
  DITNPVVKRSVSQTIKVINAIIQKYGSPOAVNIELAREMSKNFODRTNLEKEMKKROQENERAK
  QQIIELGKQNPTGQDILKYRLWNDQGGYCLYSGKKIPLEELFDGGYDIDHILPYSITFDDSYRN
  KVLVTAQENRQKGNRTPYEYFGADEKRWEDYEASVRLLVRDYKKQQKLLKKNFTEEERKEFKER
  NLNDTKYITRVVYNMIRQNLELEPFNHPEKKKQVWAVNGAVTSYLRKRWGLMQKDRSTDRHHAM
  DAVVIACCTDGMIHKISRYMQGRELAYSRNFKFPDEETGEILNRDNFTREQWDEKFGVKVPLPW
  NSFRDELDIRLLNEDPKNFLLTHADVQRELDYPGWMYGEEESPIEEGRYINYIRPLFVSRMPNH
  KVTGSAHDATIRSARDYETRGVVITKVPLTDLKLNKDNEIEGYYDKDSDRLLYQALVRQLLLHG
  NDGKKAFAEDFHKPKADGTEGPVVRKVKIEKKQTSGVMVRGGTGIAANGEMVRIDVFRENGKYY
  FVPVYTADVVRKVLPNRAATHTKPYSEWRVMDDANFVFSLYSRDLIHVKSKKDIKTNLVNGGLL
  LQKEIFAYYTGADIATASIAGFANDSNFKFRGLGIQSLEIFEKCQVDILGNISVVRHENRQEFH
  SEQ ID NO: 348
  MRVLGLDAGIASLGWALIEIEESNRGELSQGTIIGAGTWMFDAPEEKTQAGAKLKSEQRRTFRG
  QRRVVRRRRQRMNEVRRILHSHGLLPSSDRDALKQPGLDPWRIRAEALDRLLGPVELAVALGHI
  ARHRGFKSNSKGAKTNDPADDTSKMKRAVNETREKLARFGSAAKMLVEDESFVLRQTPTKNGAS
  EIVRRFRNREGDYSRSLLRDDLAAEMRALFTAQARFQSAIATADLQTAFTKAAFFQRPLQDSEK
  LVGPCPFEVDEKRAPKRGYSFELFRFLSRLNHVTLRDGKQERTLTRDELALAAADFGAAAKVSF
  TALRKKLKLPETTVFVGVKADEESKLDVVARSGKAAEGTARLRSVIVDALGELAWGALLCSPEK
  LDKIAEVISFRSDIGRISEGLAQAGCNAPLVDALTAAASDGRFDPFTGAGHISSKAARNILSGL
  RQGMTYDKACCAADYDHTASRERGAFDVGGHGREALKRILQEERISRELVGSPTARKALIESIK
  QVKAIVERYGVPDRIHVELARDVGKSIEEREEITRGIEKRNRQKDKLRGLFEKEVGRPPQDGAR
  GKEELLRFELWSEQMGRCLYTDDYISPSQLVATDDAVQVDHILPWSRFADDSYANKTLCMAKAN
  QDKKGRTPYEWFKAEKTDTEWDAFIVRVEALADMKGFKKRNYKLRNAEEAAAKFRNRNLNDTRW
  ACRLLAEALKQLYPKGEKDKDGKERRRVFSRPGALTDRLRRAWGLQWMKKSTKGDRIPDDRHHA
  LDAIVIAATTESLLQRATREVQEIEDKGLHYDLVKNVTPPWPGFREQAVEAVEKVFVARAERRR
  ARGKAHDATIRHIAVREGEQRVYERRKVAELKLADLDRVKDAERNARLIEKLRNWIEAGSPKDD
  PPLSPKGDPIFKVRLVTKSKVNIALDTGNPKRPGTVDRGEMARVDVFRKASKKGKYEYYLVPIY
  PHDIATMKTPPIRAVQAYKPEDEWPEMDSSYEFCWSLVPMTYLQVISSKGEIFEGYYRGMNRSV
  GAIQLSAHSNSSDVVQGIGARTLTEFKKFNVDRFGRKHEVERELRTWRGETWRGKAYI
  SEQ ID NO: 349
  MGNYYLGLDVGIGSIGWAVINIEKKRIEDFNVRIFKSGEIQEKNRNSRASQQCRRSRGLRRLYR
  RKSHRKLRLKNYLSIIGLTTSEKIDYYYETADNNVIQLRNKGLSEKLTPEEIAACLIHICNNRG
  YKDFYEVNVEDIEDPDERNEYKEEHDSIVLISNLMNEGGYCTPAEMICNCREFDEPNSVYRKFH
  NSAASKNHYLITRHMLVKEVDLILENQSKYYGILDDKTIAKIKDIIFAQRDFEIGPGKNERFRR
  FTGYLDSIGKCQFFKDQERGSRFTVIADIYAFVNVLSQYTYTNNRGESVFDTSFANDLINSALK
  NGSMDKRELKAIAKSYHIDISDKNSDTSLTKCFKYIKVVKPLFEKYGYDWDKLIENYTDTDNNV
  LNRIGIVLSQAQTPKRRREKLKALNIGLDDGLINELTKLKLSGTANVSYKYMQGSIEAFCEGDL
  YGKYQAKFNKEIPDIDENAKPQKLPPFKNEDDCEFFKNPVVFRSINETRKLINAIIDKYGYPAA
  VNIETADELNKTFEDRAIDTKRNNDNQKENDRIVKEIIECIKCDEVHARHLIEKYKLWEAQEGK
  CLYSGETITKEDMLRDKDKLFEVDHIVPYSLILDNTINNKALVYAEENQKKGQRTPLMYMNEAQ
  AADYRVRVNTMFKSKKCSKKKYQYLMLPDLNDQELLGGWRSRNLNDTRYICKYLVNYLRKNLRF
  DRSYESSDEDDLKIRDHYRVFPVKSRFTSMFRRWWLNEKTWGRYDKAELKKLTYLDHAADAIII
  ANCRPEYVVLAGEKLKLNKMYHQAGKRITPEYEQSKKACIDNLYKLFRMDRRTAEKLLSGHGRL
  TPIIPNLSEEVDKRLWDKNIYEQFWKDDKDKKSCEELYRENVASLYKGDPKFASSLSMPVISLK
  PDHKYRGTITGEEAIRVKEIDGKLIKLKRKSISEITAESINSIYTDDKILIDSLKTIFEQADYK
  DVGDYLKKTNQHFFTTSSGKRVNKVTVIEKVPSRWLRKEIDDNNFSLLNDSSYYCIELYKDSKG
  DNNLQGIAMSDIVHDRKTKKLYLKPDFNYPDDYYTHVMYIFPGDYLRIKSTSKKSGEQLKFEGY
  FISVKNVNENSFRFISDNKPCAKDKRVSITKKDIVIKLAVDLMGKVQGENNGKGISCGEPLSLL
  KEKN
  SEQ ID NO: 350
  MLSRQLLGASHLARPVSYSYNVQDNDVHCSYGERCFMRGKRYRIGIDVGLNSVGLAAVEVSDEN
  SPVRLLNAQSVIHDGGVDPQKNKEAITRKNMSGVARRTRRMRRRKRERLHKLDMLLGKFGYPVI
  EPESLDKPFEEWHVRAELATRYIEDDELRRESISIALRHMARHRGWRNPYRQVDSLISDNPYSK
  QYGELKEKAKAYNDDATAAEEESTPAQLVVAMLDAGYAEAPRLRWRTGSKKPDAEGYLPVRLMQ
  EDNANELKQIFRVQRVPADEWKPLFRSVFYAVSPKGSAEQRVGQDPLAPEQARALKASLAFQEY
  RIANVITNLRIKDASAELRKLTVDEKQSIYDQLVSPSSEDITWSDLCDFLGFKRSQLKGVGSLT
  EDGEERISSRPPRLTSVQRIYESDNKIRKPLVAWWKSASDNEHEAMIRLLSNTVDIDKVREDVA
  YASAIEFIDGLDDDALTKLDSVDLPSGRAAYSVETLQKLTRQMLTTDDDLHEARKTLFNVTDSW
  RPPADPIGEPLGNPSVDRVLKNVNRYLMNCQQRWGNPVSVNIEHVRSSFSSVAFARKDKREYEK
  NNEKRSIFRSSLSEQLRADEQMEKVRESDLRRLEAIQRQNGQCLYCGRTITFRTCEMDHIVPRK
  GVGSTNTRTNFAAVCAECNRMKSNTPFAIWARSEDAQTRGVSLAEAKKRVTMFTFNPKSYAPRE
  VKAFKQAVIARLQQTEDDAAIDNRSIESVAWMADELHRRIDWYFNAKQYVNSASIDDAEAETMK
  TTVSVFQGRVTASARRAAGIEGKIHFIGQQSKTRLDRRHHAVDASVIAMMNTAAAQTLMERESL
  RESQRLIGLMPGERSWKEYPYEGTSRYESFHLWLDNMDVLLELLNDALDNDRIAVMQSQRYVLG
  NSIAHDATIHPLEKVPLGSAMSADLIRRASTPALWCALTRLPDYDEKEGLPEDSHREIRVHDTR
  YSADDEMGFFASQAAQIAVQEGSADIGSAIHHARVYRCWKTNAKGVRKYFYGMIRVFQTDLLRA
  CHDDLFTVPLPPQSISMRYGEPRVVQALQSGNAQYLGSLVVGDEIEMDFSSLDVDGQIGEYLQF
  FSQFSGGNLAWKHWVVDGFFNQTQLRIRPRYLAAEGLAKAFSDDVVPDGVQKIVTKQGWLPPVN
  TASKTAVRIVRRNAFGEPRLSSAHHMPCSWQWRHE
  SEQ ID NO: 351
  MYSIGLDLGISSVGWSVIDERTGNVIDLGVRLFSAKNSEKNLERRTNRGGRRLIRRKTNRLKDA
  KKILAAVGFYEDKSLKNSCPYQLRVKGLTEPLSRGEIYKVTLHILKKRGISYLDEVDTEAAKES
  QDYKEQVRKNAQLLTKYTPGQIQLQRLKENNRVKTGINAQGNYQLNVFKVSAYANELATILKTQ
  QAFYPNELTDDWIALFVQPGIAEEAGLIYRKRPYYHGPGNEANNSPYGRWSDFQKTGEPATNIF
  DKLIGKDFQGELRASGLSLSAQQYNLLNDLTNLKIDGEVPLSSEQKEYILTELMTKEFTRFGVN
  DVVKLLGVKKERLSGWRLDKKGKPEIHTLKGYRNWRKIFAEAGIDLATLPTETIDCLAKVLTLN
  TEREGIENTLAFELPELSESVKLLVLDRYKELSQSISTQSWHRFSLKTLHLLIPELMNATSEQN
  TLLEQFQLKSDVRKRYSEYKKLPTKDVLAEIYNPTVNKTVSQAFKVIDALLVKYGKEQIRYITI
  EMPRDDNEEDEKKRIKELHAKNSQRKNDSQSYFMQKSGWSQEKFQTTIQKNRRFLAKLLYYYEQ
  DGICAYTGLPISPELLVSDSTEIDHIIPISISLDDSINNKVLVLSKANQVKGQQTPYDAWMDGS
  FKKINGKFSNWDDYQKWVESRHFSHKKENNLLETRNIFDSEQVEKFLARNLNDTRYASRLVLNT
  LQSFFTNQETKVRVVNGSFTHTLRKKWGADLDKTRETHHHHAVDATLCAVTSFVKVSRYHYAVK
  EETGEKVMREIDFETGEIVNEMSYWEFKKSKKYERKTYQVKWPNFREQLKPVNLHPRIKFSHQV
  DRKANRKLSDATIYSVREKTEVKTLKSGKQKITTDEYTIGKIKDIYTLDGWEAFKKKQDKLLMK
  DLDEKTYERLLSIAETTPDFQEVEEKNGKVKRVKRSPFAVYCEENDIPAIQKYAKKNNGPLIRS
  LKYYDGKLNKHINITKDSQGRPVEKTKNGRKVTLQSLKPYRYDIYQDLETKAYYTVQLYYSDLR
  FVEGKYGITEKEYMKKVAEQTKGQVVRFCFSLQKNDGLEIEWKDSQRYDVRFYNFQSANSINFK
  GLEQEMMPAENQFKQKPYNNGAINLNIAKYGKEGKKLRKFNTDILGKKHYLFYEKEPKNIIK
  SEQ ID NO: 352
  MYFYKNKENKLNKKVVLGLDLGIASVGWCLTDISQKEDNKFPIILHGVRLFETVDDSDDKLLNE
  TRRKKRGQRRRNRRLFTRKRDFIKYLIDNNIIELEFDKNPKILVRNFIEKYINPFSKNLELKYK
  SVTNLPIGFHNLRKAAINEKYKLDKSELIVLLYEYLSLRGAFFDNPEDTKSKEMNKNEIEIEDK
  NESIKNAEFPIDKIIEFYKISGKIRSTINLKFGHQDYLKEIKQVFEKQNIDFMNYEKFAMEEKS
  FFSRIRNYSEGPGNEKSFSKYGLYANENGNPELIINEKGQKIYTKIFKTLWESKIGKCSYDKKL
  YRAPKNSFSAKVFDITNKLTDWKHKNEYISERLKRKILLSRFLNKDSKSAVEKILKEENIKFEN
  LSEIAYNKDDNKINLPIINAYHSLTTIFKKHLINFENYLISNENDLSKLMSFYKQQSEKLFVPN
  EKGSYEINQNNNVLHIFDAISNILNKFSTIQDRIRILEGYFEFSNLKKDVKSSEIYSEIAKLRE
  FSGTSSLSFGAYYKFIPNLISEGSKNYSTISYEEKALQNQKNNFSHSNLFEKTWVEDLIASPTV
  KRSLRQTMNLLKEIFKYSEKNNLEIEKIVVEVTRSSNNKHERKKIEGINKYRKEKYEELKKVYD
  LPNENTTLLKKLWLLRQQQGYDAYSLRKIEANDVINKPWNYDIDHIVPRSISFDDSFSNLVIVN
  KLDNAKKSNDLSAKQFIEKIYGIEKLKEAKENWGNWYLRNANGKAFNDKGKFIKLYTIDNLDEF
  DNSDFINRNLSDTSYITNALVNHLTFSNSKYKYSVVSVNGKQTSNLRNQIAFVGIKNNKETERE
  WKRPEGFKSINSNDFLIREEGKNDVKDDVLIKDRSFNGHHAEDAYFITIISQYFRSFKRIERLN
  VNYRKETRELDDLEKNNIKFKEKASFDNFLLINALDELNEKLNQMRFSRMVITKKNTQLFNETL
  YSGKYDKGKNTIKKVEKLNLLDNRTDKIKKIEEFFDEDKLKENELTKLHIFNHDKNLYETLKII
  WNEVKIEIKNKNLNEKNYFKYFVNKKLQEGKISFNEWVPILDNDFKIIRKIRYIKFSSEEKETD
  EIIFSQSNFLKIDQRQNFSFHNTLYWVQIWVYKNQKDQYCFISIDARNSKFEKDEIKINYEKLK
  TQKEKLQIINEEPILKINKGDLFENEEKELFYIVGRDEKPQKLEIKYILGKKIKDQKQIQKPVK
  KYFPNWKKVNLTYMGEIFKK
  SEQ ID NO: 353
  MDNKNYRIGIDVGLNSIGFCAVEVDQHDTPLGFLNLSVYRHDAGIDPNGKKTNTTRLAMSGVAR
  RTRRLFRKRKRRLAALDRFIEAQGWTLPDHADYKDPYTPWLVRAELAQTPIRDENDLHEKLAIA
  VRHIARHRGWRSPWVPVRSLHVEQPPSDQYLALKERVEAKTLLQMPEGATPAEMVVALDLSVDV
  NLRPKNREKTDTRPENKKPGFLGGKLMQSDNANELRKIAKIQGLDDALLRELIELVFAADSPKG
  ASGELVGYDVLPGQHGKRRAEKAHPAFQRYRIASIVSNLRIRHLGSGADERLDVETQKRVFEYL
  LNAKPTADITWSDVAEEIGVERNLLMGTATQTADGERASAKPPVDVTNVAFATCKIKPLKEWWL
  NADYEARCVMVSALSHAEKLTEGTAAEVEVAEFLQNLSDEDNEKLDSFSLPIGRAAYSVDSLER
  LTKRMIENGEDLFEARVNEFGVSEDWRPPAEPIGARVGNPAVDRVLKAVNRYLMAAEAEWGAPL
  SVNIEHVREGFISKRQAVEIDRENQKRYQRNQAVRSQIADHINATSGVRGSDVTRYLAIQRQNG
  ECLYCGTAITFVNSEMDHIVPRAGLGSTNTRDNLVATCERCNKSKSNKPFAVWAAECGIPGVSV
  AEALKRVDFWIADGFASSKEHRELQKGVKDRLKRKVSDPEIDNRSMESVAWMARELAHRVQYYF
  DEKHTGTKVRVFRGSLTSAARKASGFESRVNFIGGNGKTRLDRRHHAMDAATVAMLRNSVAKTL
  VLRGNIRASERAIGAAETWKSFRGENVADRQIEESWSENMRVLVEKFNLALYNDEVSIESSLRL
  QLGNGKAHDDTITKLQMHKVGDAWSLTEIDRASTPALWCALTRQPDFTWKDGLPANEDRTIIVN
  GTHYGPLDKVGIFGKAAASLLVRGGSVDIGSAIHHARIYRIAGKKPTYGMVRVFAPDLLRYRNE
  DLFNVELPPQSVSMRYAEPKVREAIREGKAEYLGWLVVGDELLLDLSSETSGQIAELQQDFPGT
  THWTVAGFFSPSRLRLRPVYLAQEGLGEDVSEGSKSIIAGQGWRPAVNKVFGSAMPEVIRRDGL
  GRKRRFSYSGLPVSWQG
  SEQ ID NO: 354
  MRLGLDIGTSSIGWWLYETDGAGSDARITGVVDGGVRIFSDGRDPKSGASLAVDRRAARAMRRR
  RDRYLRRRATLMKVLAETGLMPADPAEAKALEALDPFALRAAGLDEPLPLPHLGRALFHLNQRR
  GFKSNRKTDRGDNESGKIKDATARLDMEMMANGARTYGEFLHKRRQKATDPRHVPSVRTRLSIA
  NRGGPDGKEEAGYDFYPDRRHLEEEFHKLWAAQGAHHPELTETLRDLLFEKIFFQRPLKEPEVG
  LCLFSGHHGVPPKDPRLPKAHPLTQRRVLYETVNQLRVTADGREARPLTREERDQVIHALDNKK
  PTKSLSSMVLKLPALAKVLKLRDGERFTLETGVRDAIACDPLRASPAHPDRFGPRWSILDADAQ
  WEVISRIRRVQSDAEHAALVDWLTEAHGLDRAHAEATAHAPLPDGYGRLGLTATTRILYQLTAD
  VVTYADAVKACGWHHSDGRTGECFDRLPYYGEVLERHVIPGSYHPDDDDITRFGRITNPTVHIG
  LNQLRRLVNRIIETHGKPHQIVVELARDLKKSEEQKRADIKRIRDTTEAAKKRSEKLEELEIED
  NGRNRMLLRLWEDLNPDDAMRRFCPYTGTRISAAMIFDGSCDVDHILPYSRTLDDSFPNRTLCL
  REANRQKRNQTPWQAWGDTPHWHAIAANLKNLPENKRWRFAPDAMTRFEGENGFLDRALKDTQY
  LARISRSYLDTLFTKGGHVWVVPGRFTEMLRRHWGLNSLLSDAGRGAVKAKNRTDHRHHAIDAA
  VIAATDPGLLNRISRAAGQGEAAGQSAELIARDTPPPWEGFRDDLRVRLDRIIVSHRADHGRID
  HAARKQGRDSTAGQLHQETAYSIVDDIHVASRTDLLSLKPAQLLDEPGRSGQVRDPQLRKALRV
  ATGGKTGKDFENALRYFASKPGPYQAIRRVRIIKPLQAQARVPVPAQDPIKAYQGGSNHLFEIW
  RLPDGEIEAQVITSFEAHTLEGEKRPHPAAKRLLRVHKGDMVALERDGRRVVGHVQKMDIANGL
  FIVPHNEANADTRNNDKSDPFKWIQIGARPAIASGIRRVSVDEIGRLRDGGTRPI
  SEQ ID NO: 355
  MLHCIAVIRVPPSEEPGFFETHADSCALCHHGCMTYAANDKAIRYRVGIDVGLRSIGFCAVEVD
  DEDHPIRILNSVVHVHDAGTGGPGETESLRKRSGVAARARRRGRAEKQRLKKLDVLLEELGWGV
  SSNELLDSHAPWHIRKRLVSEYIEDETERRQCLSVAMAHIARHRGWRNSFSKVDTLLLEQAPSD
  RMQGLKERVEDRTGLQFSEEVTQGELVATLLEHDGDVTIRGFVRKGGKATKVHGVLEGKYMQSD
  LVAELRQICRTQRVSETTFEKLVLSIFHSKEPAPSAARQRERVGLDELQLALDPAAKQPRAERA
  HPAFQKFKVVATLANMRIREQSAGERSLTSEELNRVARYLLNHTESESPTWDDVARKLEVPRHR
  LRGSSRASLETGGGLTYPPVDDTTVRVMSAEVDWLADWWDCANDESRGHMIDAISNGCGSEPDD
  VEDEEVNELISSATAEDMLKLELLAKKLPSGRVAYSLKTLREVTAAILETGDDLSQAITRLYGV
  DPGWVPTPAPIEAPVGNPSVDRVLKQVARWLKFASKRWGVPQTVNIEHTREGLKSASLLEEERE
  RWERFEARREIRQKEMYKRLGISGPFRRSDQVRYEILDLQDCACLYCGNEINFQTFEVDHIIPR
  VDASSDSRRTNLAAVCHSCNSAKGGLAFGQWVKRGDCPSGVSLENAIKRVRSWSKDRLGLTEKA
  MGKRKSEVISRLKTEMPYEEFDGRSMESVAWMAIELKKRIEGYFNSDRPEGCAAVQVNAYSGRL
  TACARRAAHVDKRVRLIRLKGDDGHHKNRFDRRNHAMDALVIALMTPAIARTIAVREDRREAQQ
  LTRAFESWKNFLGSEERMQDRWESWIGDVEYACDRLNELIDADKIPVTENLRLRNSGKLHADQP
  ESLKKARRGSKRPRPQRYVLGDALPADVINRVTDPGLWTALVRAPGFDSQLGLPADLNRGLKLR
  GKRISADFPIDYFPTDSPALAVQGGYVGLEFHHARLYRIIGPKEKVKYALLRVCAIDLCGIDCD
  DLFEVELKPSSISMRTADAKLKEAMGNGSAKQIGWLVLGDEIQIDPTKFPKQSIGKELKECGPV
  SSWRVSALDTPSKITLKPRLLSNEPLLKTSRVGGHESDLVVAECVEKIMKKTGWWEINALCQS
  GLIRVIRRNALGEVRTSPKSGLPISLNLR
  SEQ ID NO: 356
  MRYRVGLDLGTASVGAAVFSMDEQGNPMELIWHYERLFSEPLVPDMGQLKPKKAARRLARQQRR
  QIDRRASRLRRIAIVSRRLGIAPGRNDSGVHGNDVPTLRAMAVNERIELGQLRAVLLRMGKKRG
  YGGTFKAVRKVGEAGEVASGASRLEEEMVALASVQNKDSVTVGEYLAARVEHGLPSKLKVAANN
  EYYAPEYALFRQYLGLPAIKGRPDCLPNMYALRHQIEHEFERIWATQSQFHDVMKDHGVKEEIR
  NAIFFQRPLKSPADKVGRCSLQTNLPRAPRAQIAAQNFRIEKQMADLRWGMGRRAEMLNDHQKA
  VIRELLNQQKELSFRKIYKELERAGCPGPEGKGLNMDRAALGGRDDLSGNTTLAAWRKLGLEDR
  WQELDEVTQIQVINFLADLGSPEQLDTDDWSCRFMGKNGRPRNFSDEFVAFMNELRMTDGFDRL
  SKMGFEGGRSSYSIKALKALTEWMIAPHWRETPETHRVDEEAAIRECYPESLATPAQGGRQSKL
  EPPPLTGNEVVDVALRQVRHTINMMIDDLGSVPAQIVVEMAREMKGGVTRRNDIEKQNKRFASE
  RKKAAQSIEENGKTPTPARILRYQLWIEQGHQCPYCESNISLEQALSGAYTNFEHILPRTLTQI
  GRKRSELVLAHRECNDEKGNRTPYQAFGHDDRRWRIVEQRANALPKKSSRKTRLLLLKDFEGEA
  LTDESIDEFADRQLHESSWLAKVTTQWLSSLGSDVYVSRGSLTAELRRRWGLDTVIPQVRFESG
  MPVVDEEGAEITPEEFEKFRLQWEGHRVTREMRTDRRPDKRIDHRHHLVDAIVTALTSRSLYQQ
  YAKAWKVADEKQRHGRVDVKVELPMPILTIRDIALEAVRSVRISHKPDRYPDGRFFEATAYGIA
  QRLDERSGEKVDWLVSRKSLTDLAPEKKSIDVDKVRANISRIVGEAIRLHISNIFEKRVSKGMT
  PQQALREPIEFQGNILRKVRCFYSKADDCVRIEHSSRRGHHYKMLLNDGFAYMEVPCKEGILYG
  VPNLVRPSEAVGIKRAPESGDFIRFYKGDTVKNIKTGRVYTIKQILGDGGGKLILTPVTETKPA
  DLLSAKWGRLKVGGRNIHLLRLCAE
  SEQ ID NO: 357
  MIGEHVRGGCLFDDHWTPNWGAFRLPNTVRTFTKAENPKDGSSLAEPRRQARGLRRRLRRKTQR
  LEDLRRLLAKEGVLSLSDLETLFRETPAKDPYQLRAEGLDRPLSFPEWVRVLYHITKHRGFQSN
  RRNPVEDGQERSRQEEEGKLLSGVGENERLLREGGYRTAGEMLARDPKFQDHRRNRAGDYSHTL
  SRSLLLEEARRLFQSQRTLGNPHASSNLEEAFLHLVAFQNPFASGEDIRNKAGHCSLEPDQIRA
  PRRSASAETFMLLQKTGNLRLIHRRTGEERPLTDKEREQIHLLAWKQEKVTHKTLRRHLEIPEE
  WLFTGLPYHRSGDKAEEKLFVHLAGIHEIRKALDKGPDPAVWDTLRSRRDLLDSIADTLTFYKN
  EDEILPRLESLGLSPENARALAPLSFSGTAHLSLSALGKLLPHLEEGKSYTQARADAGYAAPPP
  DRHPKLPPLEEADWRNPVVFRALTQTRKVVNALVRRYGPPWCIHLETARELSQPAKVRRRIETE
  QQANEKKKQQAEREFLDIVGTAPGPGDLLKMRLWREQGGFCPYCEEYLNPTRLAEPGYAEMDHI
  LPYSRSLDNGWHNRVLVHGKDNRDKGNRTPFEAFGGDTARWDRLVAWVQASHLSAPKKRNLLRE
  DFGEEAERELKDRNLTDTRFITKTAATLLRDRLTFHPEAPKDPVMTLNGRLTAFLRKQWGLHKN
  RKNGDLHHALDAAVLAVASRSFVYRLSSHNAAWGELPRGREAENGFSLPYPAFRSEVLARLCPT
  REEILLRLDQGGVGYDEAFRNGLRPVFVSRAPSRRLRGKAHMETLRSPKWKDHPEGPRTASRIP
  LKDLNLEKLERMVGKDRDRKLYEALRERLAAFGGNGKKAFVAPFRKPCRSGEGPLVRSLRIFDS
  GYSGVELRDGGEVYAVADHESMVRVDVYAKKNRFYLVPVYVADVARGIVKNRAIVAHKSEEEWD
  LVDGSFDFRFSLFPGDLVEIEKKDGAYLGYYKSCHRGDGRLLLDRHDRMPRESDCGTFYVSTRK
  DVLSMSKYQVDPLGEIRLVGSEKPPFVL
  SEQ ID NO: 358
  MEKKRKVTLGFDLGIASVGWAIVDSETNQVYKLGSRLFDAPDTNLERRTQRGTRRLLRRRKYRN
  QKFYNLVKRTEVFGLSSREAIENRFRELSIKYPNIIELKTKALSQEVCPDEIAWILHDYLKNRG
  YFYDEKETKEDFDQQTVESMPSYKLNEFYKKYGYFKGALSQPTESEMKDNKDLKEAFFFDFSNK
  EWLKEINYFFNVQKNILSETFIEEFKKIFSFTRDISKGPGSDNMPSPYGIFGEFGDNGQGGRYE
  HIWDKNIGKCSIFTNEQRAPKYLPSALIFNFLNELANIRLYSTDKKNIQPLWKLSSVDKLNILL
  NLFNLPISEKKKKLTSTNINDIVKKESIKSIMISVEDIDMIKDEWAGKEPNVYGVGLSGLNIEE
  SAKENKFKFQDLKILNVLINLLDNVGIKFEFKDRNDIIKNLELLDNLYLFLIYQKESNNKDSSI
  DLEIAKNESLNIENLKLKLKEFLLGAGNEFENHNSKTHSLSKKAIDEILPKLLDNNEGWNLEAI
  KNYDEEIKSQIEDNSSLMAKQDKKYLNDNFLKDAILPPNVKVTFQQAILIFNKIIQKFSKDFEI
  DKVVIELAREMTQDQENDALKGIAKAQKSKKSLVEERLEANNIDKSVFNDKYEKLIYKIFLWIS
  QDFKDPYTGAQISVNEIVNNKVEIDHIIPYSLCFDDSSANKVLVHKQSNQEKSNSLPYEYIKQG
  HSGWNWDEFTKYVKRVFVNNVDSILSKKERLKKSENLLTASYDGYDKLGFLARNLNDTRYATIL
  FRDQLNNYAEHHLIDNKKMFKVIAMNGAVTSFIRKNMSYDNKLRLKDRSDFSHHAYDAAIIALF
  SNKTKTLYNLIDPSLNGIISKRSEGYWVIEDRYTGEIKELKKEDWTSIKNNVQARKIAKEIEEY
  LIDLDDEVFFSRKTKRKTNRQLYNETIYGIATKTDEDGITNYYKKEKFSILDDKDIYLRLLRER
  EKFVINQSNPEVIDQIIEIIESYGKENNIPSRDEAINIKYTKNKINYNLYLKQYMRSLTKSLDQ
  FSEEFINQMIANKTFVLYNPTKNTTRKIKFLRLVNDVKINDIRKNQVINKFNGKNNEPKAFYEN
  INSLGAIVFKNSANNFKTLSINTQIAIFGDKNWDIEDFKTYNMEKIEKYKEIYGIDKTYNFHSF
  IFPGTILLDKQNKEFYYISSIQTVRDIIEIKFLNKIEFKDENKNQDTSKTPKRLMFGIKSIMNN
  YEQVDISPFGINKKIFE
  SEQ ID NO: 359
  MGYRIGLDVGITSTGYAVLKTDKNGLPYKILTLDSVIYPRAENPQTGASLAEPRRIKRGLRRRT
  RRTKFRKQRTQQLFIHSGLLSKPEIEQILATPQAKYSVYELRVAGLDRRLTNSELFRVLYFFIG
  HRGFKSNRKAELNPENEADKKQMGQLLNSIEEIRKAIAEKGYRTVGELYLKDPKYNDHKRNKGY
  IDGYLSTPNRQMLVDEIKQILDKQRELGNEKLTDEFYATYLLGDENRAGIFQAQRDFDEGPGAG
  PYAGDQIKKMVGKDIFEPTEDRAAKATYTFQYFNLLQKMTSLNYQNTTGDTWHTLNGLDRQAII
  DAVFAKAEKPTKTYKPTDFGELRKLLKLPDDARFNLVNYGSLQTQKEIETVEKKTRFVDFKAYH
  DLVKVLPEEMWQSRQLLDHIGTALTLYSSDKRRRRYFAEELNLPAELIEKLLPLNFSKFGHLSI
  KSMQNIIPYLEMGQVYSEATTNTGYDFRKKQISKDTIREEITNPVVRRAVTKTIKIVEQIIRRY
  GKPDGINIELARELGRNFKERGDIQKRQDKNRQTNDKIAAELTELGIPVNGQNIIRYKLHKEQN
  GVDPYTGDQIPFERAFSEGYEVDHIIPYSISWDDSYTNKVLTSAKCNREKGNRIPMVYLANNEQ
  RLNALTNIADNIIRNSRKRQKLLKQKLSDEELKDWKQRNINDTRFITRVLYNYFRQAIEFNPEL
  EKKQRVLPLNGEVTSKIRSRWGFLKVREDGDLHHAIDATVIAAITPKFIQQVTKYSQHQEVKNN
  QALWHDAEIKDAEYAAEAQRMDADLFNKIFNGFPLPWPEFLDELLARISDNPVEMMKSRSWNTY
  TPIEIAKLKPVFVVRLANHKISGPAHLDTIRSAKLFDEKGIVLSRVSITKLKINKKGQVATGDG
  IYDPENSNNGDKVVYSAIRQALEAHNGSGELAFPDGYLEYVDHGTKKLVRKVRVAKKVSLPVRL
  KNKAAADNGSMVRIDVFNTGKKFVFVPIYIKDTVEQVLPNKAIARGKSLWYQITESDQFCFSLY
  PGDMVHIESKTGIKPKYSNKENNTSVVPIKNFYGYFDGADIATASILVRAHDSSYTARSIGIAG
  LLKFEKYQVDYFGRYHKVHEKKRQLFVKRDE
  SEQ ID NO: 360
  MQKNINTKQNHIYIKQAQKIKEKLGDKPYRIGLDLGVGSIGFAIVSMEENDGNVLLPKEIIMVG
  SRIFKASAGAADRKLSRGQRNNHRHTRERMRYLWKVLAEQKLALPVPADLDRKENSSEGETSAK
  RFLGDVLQKDIYELRVKSLDERLSLQELGYVLYHIAGHRGSSAIRTFENDSEEAQKENTENKKI
  AGNIKRLMAKKNYRTYGEYLYKEFFENKEKHKREKISNAANNHKFSPTRDLVIKEAEAILKKQA
  GKDGFHKELTEEYIEKLTKAIGYESEKLIPESGFCPYLKDEKRLPASHKLNEERRLWETLNNAR
  YSDPIVDIVTGEITGYYEKQFTKEQKQKLFDYLLTGSELTPAQTKKLLGLKNTNFEDIILQGRD
  KKAQKIKGYKLIKLESMPFWARLSEAQQDSFLYDWNSCPDEKLLTEKLSNEYHLTEEEIDNAFN
  EIVLSSSYAPLGKSAMLIILEKIKNDLSYTEAVEEALKEGKLTKEKQAIKDRLPYYGAVLQEST
  QKIIAKGFSPQFKDKGYKTPHTNKYELEYGRIANPVVHQTLNELRKLVNEIIDILGKKPCEIGL
  ETARELKKSAEDRSKLSREQNDNESNRNRIYEIYIRPQQQVIITRRENPRNYILKFELLEEQKS
  QCPFCGGQISPNDIINNQADIEHLFPIAESEDNGRNNLVISHSACNADKAKRSPWAAFASAAKD
  SKYDYNRILSNVKENIPHKAWRFNQGAFEKFIENKPMAARFKTDNSYISKVAHKYLACLFEKPN
  IICVKGSLTAQLRMAWGLQGLMIPFAKQLITEKESESFNKDVNSNKKIRLDNRHHALDAIVIAY
  ASRGYGNLLNKMAGKDYKINYSERNWLSKILLPPNNIVWENIDADLESFESSVKTALKNAFISV
  KHDHSDNGELVKGTMYKIFYSERGYTLTTYKKLSALKLTDPQKKKTPKDFLETALLKFKGRESE
  MKNEKIKSAIENNKRLFDVIQDNLEKAKKLLEEENEKSKAEGKKEKNINDASIYQKAISLSGDK
  YVQLSKKEPGKFFAISKPTPTTTGYGYDTGDSLCVDLYYDNKGKLCGEIIRKIDAQQKNPLKYK
  EQGFTLFERIYGGDILEVDFDIHSDKNSFRNNTGSAPENRVFIKVGTFTEITNNNIQIWFGNII
  KSTGGQDDSFTINSMQQYNPRKLILSSCGFIKYRSPILKNKEG
  SEQ ID NO: 361
  MAAFKPNPINYILGLDIGIASVGWAMVEIDEDENPICLIDLGVRVFERAEVPKTGDSLAMARRL
  ARSVRRLTRRRAHRLLRARRLLKREGVLQAADFDENGLIKSLPNTPWQLRAAALDRKLTPLEWS
  AVLLHLIKHRGYLSQRKNEGETADKELGALLKGVADNAHALQTGDFRTPAELALNKFEKESGHI
  RNQRGDYSHTFSRKDLQAELILLFEKQKEFGNPHVSGGLKEGIETLLMTQRPALSGDAVQKMLG
  HCTFEPAEPKAAKNTYTAERFIWLTKLNNLRILEQGSERPLTDTERATLMDEPYRKSKLTYAQA
  RKLLGLEDTAFFKGLRYGKDNAEASTLMEMKAYHAISRALEKEGLKDKKSPLNLSPELQDEIGT
  AFSLFKTDEDITGRLKDRIQPEILEALLKHISFDKFVQISLKALRRIVPLMEQGKRYDEACAEI
  YGDHYGKKNTEEKIYLPPIPADEIRNPVVLRALSQARKVINGVVRRYGSPARIHIETAREVGKS
  FKDRKEIEKRQEENRKDREKAAAKFREYFPNFVGEPKSKDILKLRLYEQQHGKCLYSGKEINLG
  RLNEKGYVEIDHALPFSRTWDDSFNNKVLVLGSENQNKGNQTPYEYFNGKDNSREWQEFKARVE
  TSRFPRSKKQRILLQKFDEDGFKERNLNDTRYVNRFLCQFVADRMRLTGKGKKRVFASNGQITN
  LLRGFWGLRKVRAENDRHHALDAVVVACSTVAMQQKITRFVRYKEMNAFDGKTIDKETGEVLHQ
  KTHFPQPWEFFAQEVMIRVFGKPDGKPEFEEADTPEKLRTLLAEKLSSRPEAVHEYVTPLFVSR
  APNRKMSGQGHMETVKSAKRLDEGVSVLRVPLTQLKLKDLEKMVNREREPKLYEALKARLEAHK
  DDPAKAFAEPFYKYDKAGNRTQQVKAVRVEQVQKTGVWVRNHNGIADNATMVRVDVFEKGDKYY
  LVPIYSWQVAKGILPDRAVVQGKDEEDWQLIDDSFNFKFSLHPNDLVEVITKKARMFGYFASCH
  RGTGNINIRIHDLDHKIGKNGILEGIGVKTALSFQKYQIDELGKEIRPCRLKKRPPVR
  SEQ ID NO: 362
  MQTTNLSYILGLDLGIASVGWAVVEINENEDPIGLIDVGVRIFERAEVPKTGESLALSRRLARS
  TRRLIRRRAHRLLLAKRFLKREGILSTIDLEKGLPNQAWELRVAGLERRLSAIEWGAVLLHLIK
  HRGYLSKRKNESQTNNKELGALLSGVAQNHQLLQSDDYRTPAELALKKFAKEEGHIRNQRGAYT
  HTFNRLDLLAELNLLFAQQHQFGNPHCKEHIQQYMTELLMWQKPALSGEAILKMLGKCTHEKNE
  FKAAKHTYSAERFVWLTKLNNLRILEDGAERALNEEERQLLINHPYEKSKLTYAQVRKLLGLSE
  QAIFKHLRYSKENAESATFMELKAWHAIRKALENQGLKDTWQDLAKKPDLLDEIGTAFSLYKTD
  EDIQQYLTNKVPNSVINALLVSLNFDKFIELSLKSLRKILPLMEQGKRYDQACREIYGHHYGEA
  NQKTSQLLPAIPAQEIRNPVVLRTLSQARKVINAIIRQYGSPARVHIETGRELGKSFKERREIQ
  KQQEDNRTKRESAVQKFKELFSDFSSEPKSKDILKFRLYEQQHGKCLYSGKEINIHRLNEKGYV
  EIDHALPFSRTWDDSFNNKVLVLASENQNKGNQTPYEWLQGKINSERWKNFVALVLGSQCSAAK
  KQRLLTQVIDDNKFIDRNLNDTRYIARFLSNYIQENLLLVGKNKKNVFTPNGQITALLRSRWGL
  IKARENNNRHHALDAIVVACATPSMQQKITRFIRFKEVHPYKIENRYEMVDQESGEIISPHFPE
  PWAYFRQEVNIRVFDNHPDTVLKEMLPDRPQANHQFVQPLFVSRAPTRKMSGQGHMETIKSAKR
  LAEGISVLRIPLTQLKPNLLENMVNKEREPALYAGLKARLAEFNQDPAKAFATPFYKQGGQQVK
  AIRVEQVQKSGVLVRENNGVADNASIVRTDVFIKNNKFFLVPIYTWQVAKGILPNKAIVAHKNE
  DEWEEMDEGAKFKFSLFPNDLVELKTKKEYFFGYYIGLDRATGNISLKEHDGEISKGKDGVYRV
  GVKLALSFEKYQVDELGKNRQICRPQQRQPVR
  SEQ ID NO: 363
  MGIRFAFDLGTNSIGWAVWRTGPGVFGEDTAASLDGSGVLIFKDGRNPKDGQSLATMRRVPRQS
  RKRRDRFVLRRRDLLAALRKAGLFPVDVEEGRRLAATDPYHLRAKALDESLTPHEMGRVIFHLN
  QRRGFRSNRKADRQDREKGKIAEGSKRLAETLAATNCRTLGEFLWSRHRGTPRTRSPTRIRMEG
  EGAKALYAFYPTREMVRAEFERLWTAQSRFAPDLLTPERHEEIAGILFRQRDLAPPKIGCCTFE
  PSERRLPRALPSVEARGIYERLAHLRITTGPVSDRGLTRPERDVLASALLAGKSLTFKAVRKTL
  KILPHALVNFEEAGEKGLDGALTAKLLSKPDHYGAAWHGLSFAEKDTFVGKLLDEADEERLIRR
  LVTENRLSEDAARRCASIPLADGYGRLGRTANTEILAALVEETDETGTVVTYAEAVRRAGERTG
  RNWHHSDERDGVILDRLPYYGEILQRHVVPGSGEPEEKNEAARWGRLANPTVHIGLNQLRKVVN
  RLIAAHGRPDQIVVELARELKLNREQKERLDRENRKNREENERRTAILAEHGQRDTAENKIRLR
  LFEEQARANAGIALCPYTGRAIGIAELFTSEVEIDHILPVSLTLDDSLANRVLCRREANREKRR
  QTPFQAFGATPAWNDIVARAAKLPPNKRWRFDPAALERFEREGGFLGRQLNETKYLSRLAKIYL
  GKICDPDRVYVTPGTLTGLLRARWGLNSILSDSNFKNRSDHRHHAVDAVVIGVLTRGMIQRIAH
  DAARAEDQDLDRVFRDVPVPFEDFRDHVRERVSTITVAVKPEHGKGGALHEDTSYGLVPDTDPN
  AALGNLVVRKPIRSLTAGEVDRVRDRALRARLGALAAPFRDESGRVRDAKGLAQALEAFGAENG
  IRRVRILKPDASVVTIADRRTGVPYRAVAPGENHHVDIVQMRDGSWRGFAASVFEVNRPGWRPE
  WEVKKLGGKLVMRLHKGDMVELSDKDGQRRVKVVQQIEISANRVRLSPHNDGGKLQDRHADADD
  PFRWDLATIPLLKDRGCVAVRVDPIGWTLRRSNV
  SEQ ID NO: 364
  MMEVFMGRLVLGLDIGITSVGFGIIDLDESEIVDYGVRLFKEGTAAENETRRTKRGGRRLKRRR
  VTRREDMLHLLKQAGIISTSFHPLNNPYDVRVKGLNERLNGEELATALLHLCKHRGSSVETIED
  DEAKAKEAGETKKVLSMNDQLLKSGKYVCEIQKERLRTNGHIRGHENNFKTRAYVDEAFQILSH
  QDLSNELKSAIITIISRKRMYYDGPGGPLSPTPYGRYTYFGQKEPIDLIEKMRGKCSLFPNEPR
  APKLAYSAELFNLLNDLNNLSIEGEKLTSEQKAMILKIVHEKGKITPKQLAKEVGVSLEQIRGF
  RIDTKGSPLLSELTGYKMIREVLEKSNDEHLEDHVFYDEIAEILTKTKDIEGRKKQISELSSDL
  NEESVHQLAGLTKFTAYHSLSFKALRLINEEMLKTELNQMQSITLFGLKQNNELSVKGMKNIQA
  DDTAILSPVAKRAQRETFKVVNRLREIYGEEDSIVVEMAREKNSEEQRKAIRERQKFFEMRNKQ
  VADIIGDDRKINAKLREKLVLYQEQDGKTAYSLEPIDLKLLIDDPNAYEVDHIIPISISLDDSI
  TNKVLVTHRENQEKGNLTPISAFVKGRFTKGSLAQYKAYCLKLKEKNIKTNKGYRKKVEQYLLN
  ENDIYKYDIQKEFINRNLVDTSYASRVVLNTLTTYFKQNEIPTKVFTVKGSLTNAFRRKINLKK
  DRDEDYGHHAIDALIIASMPKMRLLSTIFSRYKIEDIYDESTGEVFSSGDDSMYYDDRYFAFIA
  SLKAIKVRKFSHKIDTKPNRSVADETIYSTRVIDGKEKVVKKYKDIYDPKFTALAEDILNNAYQ
  EKYLMALHDPQTFDQIVKVVNYYFEEMSKSEKYFTKDKKGRIKISGMNPLSLYRDEHGMLKKYS
  KKGDGPAITQMKYFDGVLGNHIDISAHYQVRDKKVVLQQISPYRTDFYYSKENGYKFVTIRYKD
  VRWSEKKKKYVIDQQDYAMKKAEKKIDDTYEFQFSMHRDELIGITKAEGEALIYPDETWHNFNF
  FFHAGETPEILKFTATNNDKSNKIEVKPIHCYCKMRLMPTISKKIVRIDKYATDVVGNLYKVKK
  NTLKFEFD
  SEQ ID NO: 365
  MKKILGVDLGITSFGYAILQETGKDLYRCLDNSVVMRNNPYDEKSGESSQSIRSTQKSMRRLIE
  KRKKRIRCVAQTMERYGILDYSETMKINDPKNNPIKNRWQLRAVDAWKRPLSPQELFAIFAHMA
  KHRGYKSIATEDLIYELELELGLNDPEKESEKKADERRQVYNALRHLEELRKKYGGETIAQTIH
  RAVEAGDLRSYRNHDDYEKMIRREDIEEEIEKVLLRQAELGALGLPEEQVSELIDELKACITDQ
  EMPTIDESLFGKCTFYKDELAAPAYSYLYDLYRLYKKLADLNIDGYEVTQEDREKVIEWVEKKI
  AQGKNLKKITHKDLRKILGLAPEQKIFGVEDERIVKGKKEPRTFVPFFFLADIAKFKELFASIQ
  KHPDALQIFRELAEILQRSKTPQEALDRLRALMAGKGIDTDDRELLELFKNKRSGTRELSHRYI
  LEALPLFLEGYDEKEVQRILGFDDREDYSRYPKSLRHLHLREGNLFEKEENPINNHAVKSLASW
  ALGLIADLSWRYGPFDEIILETTRDALPEKIRKEIDKAMREREKALDKIIGKYKKEFPSIDKRL
  ARKIQLWERQKGLDLYSGKVINLSQLLDGSADIEHIVPQSLGGLSTDYNTIVTLKSVNAAKGNR
  LPGDWLAGNPDYRERIGMLSEKGLIDWKKRKNLLAQSLDEIYTENTHSKGIRATSYLEALVAQV
  LKRYYPFPDPELRKNGIGVRMIPGKVTSKTRSLLGIKSKSRETNFHHAEDALILSTLTRGWQNR
  LHRMLRDNYGKSEAELKELWKKYMPHIEGLTLADYIDEAFRRFMSKGEESLFYRDMFDTIRSIS
  YWVDKKPLSASSHKETVYSSRHEVPTLRKNILEAFDSLNVIKDRHKLTTEEFMKRYDKEIRQKL
  WLHRIGNTNDESYRAVEERATQIAQILTRYQLMDAQNDKEIDEKFQQALKELITSPIEVTGKLL
  RKMRFVYDKLNAMQIDRGLVETDKNMLGIHISKGPNEKLIFRRMDVNNAHELQKERSGILCYLN
  EMLFIFNKKGLIHYGCLRSYLEKGQGSKYIALFNPRFPANPKAQPSKFTSDSKIKQVGIGSATG
  IIKAHLDLDGHVRSYEVFGTLPEGSIEWFKEESGYGRVEDDPHH
  SEQ ID NO: 366
  MRPIEPWILGLDIGTDSLGWAVFSCEEKGPPTAKELLGGGVRLFDSGRDAKDHTSRQAERGAFR
  RARRQTRTWPWRRDRLIALFQAAGLTPPAAETRQIALALRREAVSRPLAPDALWAALLHLAHHR
  GFRSNRIDKRERAAAKALAKAKPAKATAKATAPAKEADDEAGEWEGAEAALRQRMAASGAPTVG
  ALLADDLDRGQPVRMRYNQSDRDGVVAPTRALIAEELAEIVARQSSAYPGLDWPAVTRLVLDQR
  PLRSKGAGPCAFLPGEDRALRALPTVQDFIIRQTLANLRLPSTSADEPRPLTDEEHAKALALLS
  TARFVEWPALRRALGLKRGVKFTAETERNGAKQAARGTAGNLTEAILAPLIPGWSGWDLDRKDR
  VFSDLWAARQDRSALLALIGDPRGPTRVTEDETAEAVADAIQIVLPTGRASLSAKAARAIAQAM
  APGIGYDEAVTLALGLHHSHRPRQERLARLPYYAAALPDVGLDGDPVGPPPAEDDGAAAEAYYG
  RIGNISVHIALNETRKIVNALLHRHGPILRLVMVETTRELKAGADERKRMIAEQAERERENAEI
  DVELRKSDRWMANARERRQRVRLARRQNNLCPYTSTPIGHADLLGDAYDIDHVIPLARGGRDSL
  DNMVLCQSDANKTKGDKTPWEAFHDKPGWIAQRDDFLARLDPQTAKALAWRFADDAGERVARKS
  AEDEDQGFLPRQLTDTGYIARVALRYLSLVTNEPNAVVATNGRLTGLLRLAWDITPGPAPRDLL
  PTPRDALRDDTAARRFLDGLTPPPLAKAVEGAVQARLAALGRSRVADAGLADALGLTLASLGGG
  GKNRADHRHHFIDAAMIAVTTRGLINQINQASGAGRILDLRKWPRTNFEPPYPTFRAEVMKQWD
  HIHPSIRPAHRDGGSLHAATVFGVRNRPDARVLVQRKPVEKLFLDANAKPLPADKIAEIIDGFA
  SPRMAKRFKALLARYQAAHPEVPPALAALAVARDPAFGPRGMTANTVIAGRSDGDGEDAGLITP
  FRANPKAAVRTMGNAVYEVWEIQVKGRPRWTHRVLTRFDRTQPAPPPPPENARLVMRLRRGDLV
  YWPLESGDRLFLVKKMAVDGRLALWPARLATGKATALYAQLSCPNINLNGDQGYCVQSAEGIRK
  EKIRTTSCTALGRLRLSKKAT
  SEQ ID NO: 367
  MKYTLGLDVGIASVGWAVIDKDNNKIIDLGVRCFDKAEESKTGESLATARRIARGMRRRISRRS
  QRLRLVKKLFVQYEIIKDSSEFNRIFDTSRDGWKDPWELRYNALSRILKPYELVQVLTHITKRR
  GFKSNRKEDLSTTKEGVVITSIKNNSEMLRTKNYRTIGEMIFMETPENSNKRNKVDEYIHTIAR
  EDLLNEIKYIFSIQRKLGSPFVTEKLEHDFLNIWEFQRPFASGDSILSKVGKCTLLKEELRAPT
  SCYTSEYFGLLQSINNLVLVEDNNTLTLNNDQRAKIIEYAHFKNEIKYSEIRKLLDIEPEILFK
  AHNLTHKNPSGNNESKKFYEMKSYHKLKSTLPTDIWGKLHSNKESLDNLFYCLTVYKNDNEIKD
  YLQANNLDYLIEYIAKLPTFNKFKHLSLVAMKRIIPFMEKGYKYSDACNMAELDFTGSSKLEKC
  NKLTVEPIIENVTNPVVIRALTQARKVINAIIQKYGLPYMVNIELAREAGMTRQDRDNLKKEHE
  NNRKAREKISDLIRQNGRVASGLDILKWRLWEDQGGRCAYSGKPIPVCDLLNDSLTQIDHIYPY
  SRSMDDSYMNKVLVLTDENQNKRSYTPYEVWGSTEKWEDFEARIYSMHLPQSKEKRLLNRNFIT
  KDLDSFISRNLNDTRYISRFLKNYIESYLQFSNDSPKSCVVCVNGQCTAQLRSRWGLNKNREES
  DLHHALDAAVIACADRKIIKEITNYYNERENHNYKVKYPLPWHSFRQDLMETLAGVFISRAPRR
  KITGPAHDETIRSPKHFNKGLTSVKIPLTTVTLEKLETMVKNTKGGISDKAVYNVLKNRLIEHN
  NKPLKAFAEKIYKPLKNGTNGAIIRSIRVETPSYTGVFRNEGKGISDNSLMVRVDVFKKKDKYY
  LVPIYVAHMIKKELPSKAIVPLKPESQWELIDSTHEFLFSLYQNDYLVIKTKKGITEGYYRSCH
  RGTGSLSLMPHFANNKNVKIDIGVRTAISIEKYNVDILGNKSIVKGEPRRGMEKYNSFKSN
  SEQ ID NO: 368
  MIRTLGIDIGIASIGWAVIEGEYTDKGLENKEIVASGVRVFTKAENPKNKESLALPRTLARSAR
  RRNARKKGRIQQVKHYLSKALGLDLECFVQGEKLATLFQTSKDFLSPWELRERALYRVLDKEEL
  ARVILHIAKRRGYDDITYGVEDNDSGKIKKAIAENSKRIKEEQCKTIGEMMYKLYFQKSLNVRN
  KKESYNRCVGRSELREELKTIFQIQQELKSPWVNEELIYKLLGNPDAQSKQEREGLIFYQRPLK
  GFGDKIGKCSHIKKGENSPYRACKHAPSAEEFVALTKSINFLKNLTNRHGLCFSQEDMCVYLGK
  ILQEAQKNEKGLTYSKLKLLLDLPSDFEFLGLDYSGKNPEKAVFLSLPSTFKLNKITQDRKTQD
  KIANILGANKDWEAILKELESLQLSKEQIQTIKDAKLNFSKHINLSLEALYHLLPLMREGKRYD
  EGVEILQERGIFSKPQPKNRQLLPPLSELAKEESYFDIPNPVLRRALSEFRKVVNALLEKYGGF
  HYFHIELTRDVCKAKSARMQLEKINKKNKSENDAASQLLEVLGLPNTYNNRLKCKLWKQQEEYC
  LYSGEKITIDHLKDQRALQIDHAFPLSRSLDDSQSNKVLCLTSSNQEKSNKTPYEWLGSDEKKW
  DMYVGRVYSSNFSPSKKRKLTQKNFKERNEEDFLARNLVDTGYIGRVTKEYIKHSLSFLPLPDG
  KKEHIRIISGSMTSTMRSFWGVQEKNRDHHLHHAQDAIIIACIEPSMIQKYTTYLKDKETHRLK
  SHQKAQILREGDHKLSLRWPMSNFKDKIQESIQNIIPSHHVSHKVTGELHQETVRTKEFYYQAF
  GGEEGVKKALKFGKIREINQGIVDNGAMVRVDIFKSKDKGKFYAVPIYTYDFAIGKLPNKAIVQ
  GKKNGIIKDWLEMDENYEFCFSLFKNDCIKIQTKEMQEAVLAIYKSTNSAKATIELEHLSKYAL
  KNEDEEKMFTDTDKEKNKTMTRESCGIQGLKVFQKVKLSVLGEVLEHKPRNRQNIALKTTPKHV
  SEQ ID NO: 369
  MKYSIGLDIGIASVGWSVINKDKERIEDMGVRIFQKAENPKDGSSLASSRREKRGSRRRNRRKK
  HRLDRIKNILCESGLVKKNEIEKIYKNAYLKSPWELRAKSLEAKISNKEIAQILLHIAKRRGFK
  SFRKTDRNADDTGKLLSGIQENKKIMEEKGYLTIGDMVAKDPKFNTHVRNKAGSYLFSFSRKLL
  EDEVRKIQAKQKELGNTHFTDDVLEKYIEVFNSQRNFDEGPSKPSPYYSEIGQIAKMIGNCTFE
  SSEKRTAKNTWSGERFVFLQKLNNFRIVGLSGKRPLTEEERDIVEKEVYLKKEVRYEKLRKILY
  LKEEERFGDLNYSKDEKQDKKTEKTKFISLIGNYTIKKLNLSEKLKSEIEEDKSKLDKIIEILT
  FNKSDKTIESNLKKLELSREDIEILLSEEFSGTLNLSLKAIKKILPYLEKGLSYNEACEKADYD
  YKNNGIKFKRGELLPVVDKDLIANPVVLRAISQTRKVVNAIIRKYGTPHTIHVEVARDLAKSYD
  DRQTIIKENKKRELENEKTKKFISEEFGIKNVKGKLLLKYRLYQEQEGRCAYSRKELSLSEVIL
  DESMTDIDHIIPYSRSMDDSYSNKVLVLSGENRKKSNLLPKEYFDRQGRDWDTFVLNVKAMKIH
  PRKKSNLLKEKFTREDNKDWKSRALNDTRYISRFVANYLENALEYRDDSPKKRVFMIPGQLTAQ
  LRARWRLNKVRENGDLHHALDAAVVAVTDQKAINNISNISRYKELKNCKDVIPSIEYHADEETG
  EVYFEEVKDTRFPMPWSGFDLELQKRLESENPREEFYNLLSDKRYLGWFNYEEGFIEKLRPVFV
  SRMPNRGVKGQAHQETIRSSKKISNQIAVSKKPLNSIKLKDLEKMQGRDTDRKLYEALKNRLEE
  YDDKPEKAFAEPFYKPTNSGKRGPLVRGIKVEEKQNVGVYVNGGQASNGSMVRIDVFRKNGKFY
  TVPIYVHQTLLKELPNRAINGKPYKDWDLIDGSFEFLYSFYPNDLIEIEFGKSKSIKNDNKLTK
  TEIPEVNLSEVLGYYRGMDTSTGAATIDTQDGKIQMRIGIKTVKNIKKYQVDVLGNVYKVKREK
  RQTF
  SEQ ID NO: 370
  MSKKVSRRYEEQAQEICQRLGSRPYSIGLDLGVGSIGVAVAAYDPIKKQPSDLVFVSSRIFIPS
  TGAAERRQKRGQRNSLRHRANRLKFLWKLLAERNLMLSYSEQDVPDPARLRFEDAVVRANPYEL
  RLKGLNEQLTLSELGYALYHIANHRGSSSVRTFLDEEKSSDDKKLEEQQAMTEQLAKEKGISTF
  IEVLTAFNTNGLIGYRNSESVKSKGVPVPTRDIISNEIDVLLQTQKQFYQEILSDEYCDRIVSA
  ILFENEKIVPEAGCCPYFPDEKKLPRCHFLNEERRLWEAINNARIKMPMQEGAAKRYQSASFSD
  EQRHILFHIARSGTDITPKLVQKEFPALKTSIIVLQGKEKAIQKIAGFRFRRLEEKSFWKRLSE
  EQKDDFFSAWTNTPDDKRLSKYLMKHLLLTENEVVDALKTVSLIGDYGPIGKTATQLLMKHLED
  GLTYTEALERGMETGEFQELSVWEQQSLLPYYGQILTGSTQALMGKYWHSAFKEKRDSEGFFKP
  NTNSDEEKYGRIANPVVHQTLNELRKLMNELITILGAKPQEITVELARELKVGAEKREDIIKQQ
  TKQEKEAVLAYSKYCEPNNLDKRYIERFRLLEDQAFVCPYCLEHISVADIAAGRADVDHIFPRD
  DTADNSYGNKVVAHRQCNDIKGKRTPYAAFSNTSAWGPIMHYLDETPGMWRKRRKFETNEEEYA
  KYLQSKGFVSRFESDNSYIAKAAKEYLRCLFNPNNVTAVGSLKGMETSILRKAWNLQGIDDLLG
  SRHWSKDADTSPTMRKNRDDNRHHGLDAIVALYCSRSLVQMINTMSEQGKRAVEIEAMIPIPGY
  ASEPNLSFEAQRELFRKKILEFMDLHAFVSMKTDNDANGALLKDTVYSILGADTQGEDLVFVVK
  KKIKDIGVKIGDYEEVASAIRGRITDKQPKWYPMEMKDKIEQLQSKNEAALQKYKESLVQAAAV
  LEESNRKLIESGKKPIQLSEKTISKKALELVGGYYYLISNNKRTKTFVVKEPSNEVKGFAFDTG
  SNLCLDFYHDAQGKLCGEIIRKIQAMNPSYKPAYMKQGYSLYVRLYQGDVCELRASDLTEAESN
  LAKTTHVRLPNAKPGRTFVIIITFTEMGSGYQIYFSNLAKSKKGQDTSFTLTTIKNYDVRKVQL
  SSAGLVRYVSPLLVDKIEKDEVALCGE
  SEQ ID NO: 371
  MNQKFILGLDIGITSVGYGLIDYETKNIIDAGVRLFPEANVENNEGRRSKRGSRRLKRRRIHRL
  ERVKKLLEDYNLLDQSQIPQSTNPYAIRVKGLSEALSKDELVIALLHIAKRRGIHKIDVIDSND
  DVGNELSTKEQLNKNSKLLKDKFVCQIQLERMNEGQVRGEKNRFKTADIIKEIIQLLNVQKNFH
  QLDENFINKYIELVEMRREYFEGPGKGSPYGWEGDPKAWYETLMGHCTYFPDELRSVKYAYSAD
  LFNALNDLNNLVIQRDGLSKLEYHEKYHIIENVFKQKKKPTLKQIANEINVNPEDIKGYRITKS
  GKPQFTEFKLYHDLKSVLFDQSILENEDVLDQIAEILTIYQDKDSIKSKLTELDILLNEEDKEN
  IAQLTGYTGTHRLSLKCIRLVLEEQWYSSRNQMEIFTHLNIKPKKINLTAANKIPKAMIDEFIL
  SPVVKRTFGQAINLINKIIEKYGVPEDIIIELARENNSKDKQKFINEMQKKNENTRKRINEIIG
  KYGNQNAKRLVEKIRLHDEQEGKCLYSLESIPLEDLLNNPNHYEVDHIIPRSVSFDNSYHNKVL
  VKQSENSKKSNLTPYQYFNSGKSKLSYNQFKQHILNLSKSQDRISKKKKEYLLEERDINKFEVQ
  KEFINRNLVDTRYATRELTNYLKAYFSANNMNVKVKTINGSFTDYLRKVWKFKKERNHGYKHHA
  EDALIIANADFLFKENKKLKAVNSVLEKPEIESKQLDIQVDSEDNYSEMFIIPKQVQDIKDFRN
  FKYSHRVDKKPNRQLINDTLYSTRKKDNSTYIVQTIKDIYAKDNTTLKKQFDKSPEKFLMYQHD
  PRTFEKLEVIMKQYANEKNPLAKYHEETGEYLTKYSKKNNGPIVKSLKYIGNKLGSHLDVTHQF
  KSSTKKLVKLSIKPYRFDVYLTDKGYKFITISYLDVLKKDNYYYIPEQKYDKLKLGKAIDKNAK
  FIASFYKNDLIKLDGEIYKIIGVNSDTRNMIELDLPDIRYKEYCELNNIKGEPRIKKTIGKKVN
  SIEKLTTDVLGNVFTNTQYTKPQLLFKRGN
  SEQ ID NO: 372
  MIMKLEKWRLGLDLGTNSIGWSVFSLDKDNSVQDLIDMGVRIFSDGRDPKTKEPLAVARRTARS
  QRKLIYRRKLRRKQVFKFLQEQGLFPKTKEECMTLKSLNPYELRIKALDEKLEPYELGRALFNL
  AVRRGFKSNRKDGSREEVSEKKSPDEIKTQADMQTHLEKAIKENGCRTITEFLYKNQGENGGIR
  FAPGRMTYYPTRKMYEEEFNLIRSKQEKYYPQVDWDDIYKAIFYQRPLKPQQRGYCIYENDKER
  TFKAMPCSQKLRILQDIGNLAYYEGGSKKRVELNDNQDKVLYELLNSKDKVTFDQMRKALCLAD
  SNSFNLEENRDFLIGNPTAVKMRSKNRFGKLWDEIPLEEQDLIIETIITADEDDAVYEVIKKYD
  LTQEQRDFIVKNTILQSGTSMLCKEVSEKLVKRLEEIADLKYHEAVESLGYKFADQTVEKYDLL
  PYYGKVLPGSTMEIDLSAPETNPEKHYGKISNPTVHVALNQTRVVVNALIKEYGKPSQIAIELS
  RDLKNNVEKKAEIARKQNQRAKENIAINDTISALYHTAFPGKSFYPNRNDRMKYRLWSELGLGN
  KCIYCGKGISGAELFTKEIEIEHILPFSRTLLDAESNLTVAHSSCNAFKAERSPFEAFGTNPSG
  YSWQEIIQRANQLKNTSKKNKFSPNAMDSFEKDSSFIARQLSDNQYIAKAALRYLKCLVENPSD
  VWTTNGSMTKLLRDKWEMDSILCRKFTEKEVALLGLKPEQIGNYKKNRFDHRHHAIDAVVIGLT
  DRSMVQKLATKNSHKGNRIEIPEFPILRSDLIEKVKNIVVSFKPDHGAEGKLSKETLLGKIKLH
  GKETFVCRENIVSLSEKNLDDIVDEIKSKVKDYVAKHKGQKIEAVLSDFSKENGIKKVRCVNRV
  QTPIEITSGKISRYLSPEDYFAAVIWEIPGEKKTFKAQYIRRNEVEKNSKGLNVVKPAVLENGK
  PHPAAKQVCLLHKDDYLEFSDKGKMYFCRIAGYAATNNKLDIRPVYAVSYCADWINSTNETMLT
  GYWKPTPTQNWVSVNVLFDKQKARLVTVSPIGRVFRK
  SEQ ID NO: 373
  MSSKAIDSLEQLDLFKPQEYTLGLDLGIKSIGWAILSGERIANAGVYLFETAEELNSTGNKLIS
  KAAERGRKRRIRRMLDRKARRGRHIRYLLEREGLPTDELEEVVVHQSNRTLWDVRAEAVERKLT
  KQELAAVLFHLVRHRGYFPNTKKLPPDDESDSADEEQGKINRATSRLREELKASDCKTIGQFLA
  QNRDRQRNREGDYSNLMARKLVFEEALQILAFQRKQGHELSKDFEKTYLDVLMGQRSGRSPKLG
  NCSLIPSELRAPSSAPSTEWFKFLQNLGNLQISNAYREEWSIDAPRRAQIIDACSQRSTSSYWQ
  IRRDFQIPDEYRFNLVNYERRDPDVDLQEYLQQQERKTLANFRNWKQLEKIIGTGHPIQTLDEA
  ARLITLIKDDEKLSDQLADLLPEASDKAITQLCELDFTTAAKISLEAMYRILPHMNOGMGFFDA
  CQQESLPEIGVPPAGDRVPPFDEMYNPVVNRVLSQSRKLINAVIDEYGMPAKIRVELARDLGKG
  RELRERIKLDQLDKSKONDQRAEDFRAEFQQAPRGDQSLRYRLWKEQNCTCPYSGRMIPVNSVL
  SEDTQIDHILPISQSFDNSLSNKVLCFTEENAQKSNRTPFEYLDAADFQRLEAISGNWPEAKRN
  KLLHKSFGKVAEEWKSRALNDTRYLTSALADHLRHHLPDSKIQTVNGRITGYLRKQWGLEKDRD
  KHTHHAVDAIVVACTTPAIVQQVTLYHQDIRRYKKLGEKRPTPWPETFRQDVLDVEEEIFITRQ
  PKKVSGGIQTKDTLRKHRSKPDRQRVALTKVKLADLERLVEKDASNRNLYEHLKQCLEESGDQP
  TKAFKAPFYMPSGPEAKQRPILSKVTLLREKPEPPKQLTELSGGRRYDSMAQGRLDIYRYKPGG
  KRKDEYRVVLQRMIDLMRGEENVHVFQKGVPYDQGPEIEQNYTFLFSLYFDDLVEFQRSADSEV
  IRGYYRTFNIANGQLKISTYLEGRQDFDFFGANRLAHFAKVQVNLLGKVIK
  SEQ ID NO: 374
  MRSLRYRLALDLGSTSLGWALFRLDACNRPTAVIKAGVRIFSDGRNPKDGSSLAVTRRAARAMR
  RRRDRLLKRKTRMQAKLVEHGFFPADAGKRKALEQLNPYALRAKGLQEALLPGEFARALFHINQ
  RRGFKSNRKTDKKDNDSGVLKKAIGQLRQQMAEQGSRTVGEYLWTRLQQGQGVRARYREKPYTT
  EEGKKRIDKSYDLYIDRAMIEQEFDALWAAQAAFNPTLFHEAARADLKDTLLHQRPLRPVKPGR
  CTLLPEEERAPLALPSTORFRIHQEVNHLRLLDENLREVALTLAQRDAVVTALETKAKLSFEQI
  RKLLKLSGSVQFNLEDAKRTELKGNATSAALARKELFGAAWSGFDEALQDEIVWQLVTEEGEGA
  LIAWLQTHTGVDEARAQAIVDVSLPEGYGNLSRKALARIVPALRAAVITYDKAVQAAGFDHHSQ
  LGFEYDASEVEDLVHPETGEIRSVFKQLPYYGKALQRHVAFGSGKPEDPDEKRYGKIANPTVHI
  GLNQVRMVVNALIRRYGRPTEVVIELARDLKQSREQKVEAQRRQADNQRRNARIRRSIAEVLGI
  GEERVRGSDIQKWICWEELSFDAADRRCPYSGVQISAAMLLSDEVEVEHILPFSKTLDDSLNNR
  TVAMRQANRIKRNRTPWDARAEFEAQGWSYEDILQRAERMPLRKRYRFAPDGYERWLGDDKDFL
  ARALNDTRYLSRVAAEYLRLVCPGTRVIPGQLTALLRGKFGLNDVLGLDGEKNRNDHRHHAVDA
  CVIGVTDQGLMQRFATASAQARGDGLTRLVDGMPMPWPTYRDHVERAVRHIWVSHRPDHGFEGA
  MMEETSYGIRKDGSIKQRRKADGSAGREISNLIRIHEATQPLRHGVSADGQPLAYKGYVGGSNY
  CIEITVNDKGKWEGEVISTFRAYGVVRAGGMGRLRNPHEGQNGRKLIMRLVIGDSVRLEVDGAE
  RTMRIVKISGSNGQIFMAPIHEANVDARNTDKQDAFTYTSKYAGSLQKAKTRRVTISPIGEVRD
  PGFKG
  SEQ ID NO: 375
  MARPAFRAPRREHVNGWTPDPHRISKPFFILVSWHLLSRVVIDSSSGCFPGTSRDHTDKFAEWE
  CAVQPYRLSFDLGTNSIGWGLLNLDRQGKPREIRALGSRIFSDGRDPQDKASLAVARRLARQMR
  RRRDRYLTRRTRLMGALVRFGLMPADPAARKRLEVAVDPYLARERATRERLEPFEIGRALFHLN
  QRRGYKPVRTATKPDEEAGKVKEAVERLEAAIAAAGAPTLGAWFAWRKTRGETLRARLAGKGKE
  AAYPFYPARRMLEAEFDTLWAEQARHHPDLLTAEAREILRHRIFHQRPLKPPPVGRCTLYPDDG
  RAPRALPSAQRLRLFQELASLRVIHLDLSERPLTPAERDRIVAFVQGRPPKAGRKPGKVQKSVP
  FEKLRGLLELPPGTGFSLESDKRPELLGDETGARIAPAFGPGWTALPLEEQDALVELLLTEAEP
  ERAIAALTARWALDEATAAKLAGATLPDFHGRYGRRAVAELLPVLERETRGDPDGRVRPIRLDE
  AVKLLRGGKDHSDFSREGALLDALPYYGAVLERHVAFGTGNPADPEEKRVGRVANPTVHIALNQ
  LRHLVNAILARHGRPEEIVIELARDLKRSAEDRRREDKRQADNQKRNEERKRLILSLGERPTPR
  NLLKLRLWEEQGPVENRRCPYSGETISMRMLLSEQVDIDHILPFSVSLDDSAANKVVCLREANR
  IKRNRSPWEAFGHDSERWAGILARAEALPKNKRWRFAPDALEKLEGEGGLRARHLNDTRHLSRL
  AVEYLRCVCPKVRVSPGRLTALLRRRWGIDAILAEADGPPPEVPAETLDPSPAEKNRADHRHHA
  LDAVVIGCIDRSMVQRVQLAAASAEREAAAREDNIRRVLEGFKEEPWDGFRAELERRARTIVVS
  HRPEHGIGGALHKETAYGPVDPPEEGFNLVVRKPIDGLSKDEINSVRDPRLRRALIDRLAIRRR
  DANDPATALAKAAEDLAAQPASRGIRRVRVLKKESNPIRVEHGGNPSGPRSGGPFHKLLLAGEV
  HHVDVALRADGRRWVGHWVTLFEAHGGRGADGAAAPPRLGDGERFLMRLHKGDCLKLEHKGRVR
  VMQVVKLEPSSNSVVVVEPHQVKTDRSKHVKISCDQLRARGARRVTVDPLGRVRVHAPGARVGI
  GGDAGRTAMEPAEDIS
  SEQ ID NO: 376
  MKRTSLRAYRLGVDLGANSLGWFVVWLDDHGQPEGLGPGGVRIFPDGRNPQSKQSNAAGRRLAR
  SARRRRDRYLQRRGKLMGLLVKHGLMPADEPARKRLECLDPYGLRAKALDEVLPLHHVGRALFH
  LNQRRGLFANRAIEQGDKDASAIKAAAGRLQTSMQACGARTLGEFLNRRHQLRATVRARSPVGG
  DVQARYEFYPTRAMVDAEFEAIWAAQAPHHPTMTAEAHDTIREAIFSQRAMKRPSIGKCSLDPA
  TSQDDVDGFRCAWSHPLAQRFRIWQDVRNLAVVETGPTSSRLGKEDQDKVARALLQTDQLSFDE
  IRGLLGLPSDARFNLESDRRDHLKGDATGAILSARRHFGPAWHDRSLDRQIDIVALLESALDEA
  AIIASLGTTHSLDEAAAQRALSALLPDGYCRLGLRAIKRVLPLMEAGRTYAEAASAAGYDHALL
  PGGKLSPTGYLPYYGQWLQNDVVGSDDERDTNERRWGRLPNPTVHIGIGQLRRVVNELIRWHGP
  PAEITVELTRDLKLSPRRLAELEREQAENQRKNDKRTSLLRKLGLPASTHNLLKLRLWDEQGDV
  ASECPYTGEAIGLERLVSDDVDIDHLIPFSISWDDSAANKVVCMRYANREKGNRTPFEAFGHRQ
  GRPYDWADIAERAARLPRGKRWRFGPGARAQFEELGDFQARLLNETSWLARVAKQYLAAVTHPH
  RIHVLPGRLTALLRATWELNDLLPGSDDRAAKSRKDHRHHAIDALVAALTDQALLRRMANAHDD
  TRRKIEVLLPWPTFRIDLETRLKAMLVSHKPDHGLQARLHEDTAYGTVEHPETEDGANLVYRKT
  FVDISEKEIDRIRDRRLRDLVRAHVAGERQQGKTLKAAVLSFAQRRDIAGHPNGIRHVRLTKSI
  KPDYLVPIRDKAGRIYKSYNAGENAFVDILQAESGRWIARATTVFQANQANESHDAPAAQPIMR
  VFKGDMLRIDHAGAEKFVKIVRLSPSNNLLYLVEHHQAGVFQTRHDDPEDSFRWLFASFDKLRE
  WNAELVRIDTLGQPWRRKRGLETGSEDATRIGWTRPKKWP
  SEQ ID NO: 377
  MERIFGFDIGTTSIGFSVIDYSSTQSAGNIQRLGVRIFPEARDPDGTPLNQQRRQKRMMRRQLR
  RRRIRRKALNETLHEAGFLPAYGSADWPVVMADEPYELRRRGLEEGLSAYEFGRAIYHLAQHRH
  FKGRELEESDTPDPDVDDEKEAANERAATLKALKNEQTTLGAWLARRPPSDRKRGIHAHRNVVA
  EEFERLWEVQSKFHPALKSEEMRARISDTIFAQRPVFWRKNTLGECRFMPGEPLCPKGSWLSQQ
  RRMLEKLNNLAIAGGNARPLDAEERDAILSKLQQQASMSWPGVRSALKALYKQRGEPGAEKSLK
  FNLELGGESKLLGNALEAKLADMFGPDWPAHPRKQEIRHAVHERLWAADYGETPDKKRVIILSE
  KDRKAHREAAANSFVADFGITGEQAAQLQALKLPTGWEPYSIPALNLFLAELEKGERFGALVNG
  PDWEGWRRTNFPHRNQPTGEILDKLPSPASKEERERISQLRNPTVVRTQNELRKVVNNLIGLYG
  KPDRIRIEVGRDVGKSKREREEIQSGIRRNEKQRKKATEDLIKNGIANPSRDDVEKWILWKEGQ
  ERCPYTGDQIGFNALFREGRYEVEHIWPRSRSFDNSPRNKTLCRKDVNIEKGNRMPFEAFGHDE
  DRWSAIQIRLQGMVSAKGGTGMSPGKVKRFLAKTMPEDFAARQLNDTRYAAKQILAQLKRLWPD
  MGPEAPVKVEAVTGQVTAQLRKLWTLNNILADDGEKTRADHRHHAIDALTVACTHPGMTNKLSR
  YWQLRDDPRAEKPALTPPWDTIRADAEKAVSEIVVSHRVRKKVSGPLHKETTYGDTGTDIKTKS
  GTYRQFVTRKKIESLSKGELDEIRDPRIKEIVAAHVAGRGGDPKKAFPPYPCVSPGGPEIRKVR
  LTSKQQLNLMAQTGNGYADLGSNHHIAIYRLPDGKADFEIVSLFDASRRLAQRNPIVQRTRADG
  ASFVMSLAAGEAIMIPEGSKKGIWIVQGVWASGQVVLERDTDADHSTTTRPMPNPILKDDAKKV
  SIDPIGRVRPSND
  SEQ ID NO: 378
  MNKRILGLDTGTNSLGWAVVDWDEHAQSYELIKYGDVIFQEGVKIEKGIESSKAAERSGYKAIR
  KQYFRRRLRKIQVLKVLVKYHLCPYLSDDDLRQWHLQKQYPKSDELMLWQRTSDEEGKNPYYDR
  HRCLHEKLDLTVEADRYTLGRALYHLTQRRGFLSNRLDTSADNKEDGVVKSGISQLSTEMEEAG
  CEYLGDYFYKLYDAQGNKVRIRQRYTDRNKHYQHEFDAICEKQELSSELIEDLQRAIFFQLPLK
  SQRHGVGRCTFERGKPRCADSHPDYEEFRMLCFVNNIQVKGPHDLELRPLTYEEREKIEPLFFR
  KSKPNFDFEDIAKALAGKKNYAWIHDKEERAYKENYRMTQGVPGCPTIAQLKSIFGDDWKTGIA
  ETYTLIQKKNGSKSLQEMVDDVWNVLYSFSSVEKLKEFAHHKLQLDEESAEKFAKIKLSHSFAA
  LSLKAIRKFLPFLRKGMYYTHASFFANIPTIVGKEIWNKEQNRKYIMENVGELVFNYQPKHREV
  QGTIEMLIKDFLANNFELPAGATDKLYHPSMIETYPNAQRNEFGILQLGSPRTNAIRNPMAMRS
  LHILRRVVNQLLKESIIDENTEVHVEYARELNDANKRRAIADRQKEQDKQHKKYGDEIRKLYKE
  ETGKDIEPTQTDVLKFQLWEEQNHHCLYTGEQIGITDFIGSNPKFDIEHTIPQSVGGDSTQMNL
  TLCDNRFNREVKKAKLPTELANHEEILTRIEPWKNKYEQLVKERDKQRTFAGMDKAVKDIRIQK
  RHKLQMEIDYWRGKYERFTMTEVPEGFSRRQGTGIGLISRYAGLYLKSLFHQADSRNKSNVYVV
  KGVATAEFRKMWGLQSEYEKKCRDNHSHHCMDAITIACIGKREYDLMAEYYRMEETFKQGRGSK
  PKFSKPWATFTEDVLNIYKNLLVVHDTPNNMPKHTKKYVQTSIGKVLAQGDTARGSLHLDTYYG
  AIERDGEIRYVVRRPLSSFTKPEELENIVDETVKRTIKEAIADKNFKQAIAEPIYMNEEKGILI
  KKVRCFAKSVKQPINIRQHRDLSKKEYKQQYHVMNENNYLLAIYEGLVKNKVVREFEIVSYIEA
  AKYYKRSQDRNIFSSIVPTHSTKYGLPLKTKLLMGQLVLMFEENPDEIQVDNTKDLVKRLYKVV
  GIEKDGRIKFKYHQEARKEGLPIFSTPYKNNDDYAPIFRQSINNINILVDGIDFTIDILGKVTL
  KE
  SEQ ID NO: 379
  MNYKMGLDIGIASVGWAVINLDLKRIEDLGVRIFDKAEHPQNGESLALPRRIARSARRRLRRRK
  HRLERIRRLLVSENVLTKEEMNLLFKQKKQIDVWQLRVDALERKLNNDELARVLLHLAKRRGFK
  SNRKSERNSKESSEFLKNIEENQSILAQYRSVGEMIVKDSKFAYHKRNKLDSYSNMIARDDLER
  EIKLIFEKQREFNNPVCTERLEEKYLNIWSSQRPFASKEDIEKKVGFCTFEPKEKRAPKATYTF
  QSFIVWEHINKLRLVSPDETRALTEIERNLLYKQAFSKNKMTYYDIRKLLNLSDDIHFKGLLYD
  PKSSLKQIENIRFLELDSYHKIRKCIENVYGKDGIRMFNETDIDTFGYALTIFKDDEDIVAYLQ
  NEYITKNGKRVSNLANKVYDKSLIDELLNLSFSKFAHLSMKAIRNILPYMEQGEIYSKACELAG
  YNFTGPKKKEKALLLPVIPNIANPVVMRALTQSRKVVNAIIKKYGSPVSIHIELARDLSHSFDE
  RKKIQKDQTENRKKNETAIKQLIEYELTKNPTGLDIVKFKLWSEQQGRCMYSLKPIELERLLEP
  GYVEVDHILPYSRSLDDSYANKVLVLTKENREKGNHTPVEYLGLGSERWKKFEKFVLANKQFSK
  KKKQNLLRLRYEETEEKEFKERNLNDTRYISKFFANFIKEHLKFADGDGGQKVYTINGKITAHL
  RSRWDFNKNREESDLHHAVDAVIVACATQGMIKKITEFYKAREQNKESAKKKEPIFPQPWPHFA
  DELKARLSKFPQESIEAFALGNYDRKKLESLRPVFVSRMPKRSVTGAAHQETLRRCVGIDEQSG
  KIQTAVKTKLSDIKLDKDGHFPMYQKESDPRTYEAIRQRLLEHNNDPKKAFQEPLYKPKKNGEP
  GPVIRTVKIIDTKNKVVHLDGSKTVAYNSNIVRTDVFEKDGKYYCVPVYTMDIMKGTLPNKAIE
  ANKPYSEWKEMTEEYTFQFSLFPNDLVRIVLPREKTIKTSTNEEIIIKDIFAYYKTIDSATGGL
  ELISHDRNFSLRGVGSKTLKRFEKYQVDVLGNIHKVKGEKRVGLAAPTNQKKGKTVDSLQSVSD
  SEQ ID NO: 380
  MRRLGLDLGTNSIGWCLLDLGDDGEPVSIFRTGARIFSDGRDPKSLGSLKATRREARLTRRRRD
  REIQRQKNLINALVKYGLMPADEIQRQALAYKDPYPIRKKALDEAIDPYEMGRAIFHINQRRGF
  KSNRKSADNEAGVVKQSIADLEMKLGEAGARTIGEFLADRQATNDTVRARRLSGTNALYEFYPD
  RYMLEQEFDTLWAKQAAFNPSLYIEAARERLKEIVFFQRKLKPQEVGRCIFLSDEDRISKALPS
  FQRFRIYQELSNLAWIDHDGVAHRITASLALRDHLFDELEHKKKLTFKAMRAILRKQGVVDYPV
  GFNLESDNRDHLIGNLTSCIMRDAKKMIGSAWDRLDEEEQDSFILMLQDDQKGDDEVRSILTQQ
  YGLSDDVAEDCLDVRLPDGHGSLSKKAIDRILPVLRDQGLIYYDAVKEAGLGEANLYDPYAALS
  DKLDYYGKALAGHVMGASGKFEDSDEKRYGTISNPTVHIALNQVRAVVNELIRLHGKPDEVVIE
  IGRDLPMGADGKRELERFQKEGRAKNERARDELKKLGHIDSRESRQKFQLWEQLAKEPVDRCCP
  FTGKMMSISDLFSDKVEIEHLLPFSLTLDDSMANKTVCFRQANRDKGNRAPFDAFGNSPAGYDW
  QEILGRSQNLPYAKRWRFLPDAMKRFEADGGFLERQLNDTRYISRYTTEYISTIIPKNKIWVVT
  GRLTSLLRGFWGLNSILRGHNTDDGTPAKKSRDDHRHHAIDAIVVGMTSRGLLQKVSKAARRSE
  DLDLTRLFEGRIDPWDGFRDEVKKHIDAIIVSHRPRKKSQGALHNDTAYGIVEHAENGASTVVH
  RVPITSLGKQSDIEKVRDPLIKSALLNETAGLSGKSFENAVQKWCADNSIKSLRIVETVSIIPI
  TDKEGVAYKGYKGDGNAYMDIYQDPTSSKWKGEIVSRFDANQKGFIPSWQSQFPTARLIMRLRI
  NDLLKLQDGEIEEIYRVQRLSGSKILMAPHTEANVDARDRDKNDTFKLTSKSPGKLQSASARKV
  HISPTGLIREG
  SEQ ID NO: 381
  MKNILGLDLGLSSIGWSVIRENSEEQELVAMGSRVVSLTAAELSSFTQGNGVSINSQRTQKRTQ
  RKGYDRYQLRRTLLRNKLDTLGMLPDDSLSYLPKLQLWGLRAKAVTQRIELNELGRVLLHLNQK
  RGYKSIKSDFSGDKKITDYVKTVKTRYDELKEMRLTIGELFFRRLTENAFFRCKEQVYPRQAYV
  EEFDCIMNCQRKFYPDILTDETIRCIRDEIIYYQRPLKSCKYLVSRCEFEKRFYLNAAGKKTEA
  GPKVSPRTSPLFQVCRLWESINNIVVKDRRNEIVFISAEQRAALFDFLNTHEKLKGSDLLKLLG
  LSKTYGYRLGEQFKTGIQGNKTRVEIERALGNYPDKKRLLQFNLQEESSSMVNTETGEIIPMIS
  LSFEQEPLYRLWHVLYSIDDREQLQSVLRQKFGIDDDEVLERLSAIDLVKAGFGNKSSKAIRRI
  LPFLQLGMNYAEACEAAGYNHSNNYTKAENEARALLDRLPAIKKNELRQPVVEKILNQMVNVVN
  ALMEKYGRFDEIRVELARELKQSKEERSNTYKSINKNQRENEQIAKRIVEYGVPTRSRIQKYKM
  WEESKHCCIYCGQPVDVGDFLRGFDVEVEHIIPKSLYFDDSFANKVCSCRSCNKEKNNRTAYDY
  MKSKGEKALSDYVERVNTMYTNNQISKTKWQNLLTPVDKISIDFIDRQLRESQYIARKAKEILT
  SICYNVTATSGSVTSFLRHVWGWDTVLHDLNFDRYKKVGLTEVIEVNHRGSVIRREQIKDWSKR
  FDHRHHAIDALTIACTKQAYIQRLNNLRAEEGPDFNKMSLERYIQSQPHFSVAQVREAVDRILV
  SFRAGKRAVTPGKRYIRKNRKRISVQSVLIPRGALSEESVYGVIHVWEKDEQGHVIQKQRAVMK
  YPITSINREMLDKEKVVDKRIHRILSGRLAQYNDNPKEAFAKPVYIDKECRIPIRTVRCFAKPA
  INTLVPLKKDDKGNPVAWVNPGNNHHVAIYRDEDGKYKERTVTFWEAVDRCRVGIPAIVTQPDT
  IWDNILQRNDISENVLESLPDVKWQFVLSLQQNEMFILGMNEEDYRYAMDQQDYALLNKYLYRV
  QKLSKSDYSFRYHTETSVEDKYDGKPNLKLSMQMGKLKRVSIKSLLGLNPHKVHISVLGEIKEI
  S
  SEQ ID NO: 382
  MAEKQHRWGLDIGTNSIGWAVIALIEGRPAGLVATGSRIFSDGRNPKDGSSLAVERRGPRQMRR
  RRDRYLRRRDRFMQALINVGLMPGDAAARKALVTENPYVLRQRGLDQALTLPEFGRALFHLNQR
  RGFQSNRKTDRATAKESGKVKNAIAAFRAGMGNARTVGEALARRLEDGRPVRARMVGQGKDEHY
  ELYIAREWIAQEFDALWASQQRFHAEVLADAARDRLRAILLFQRKLLPVPVGKCELEPNQPRVA
  AALPSAQRFRLMQELNHLRVMTLADKRERPLSFQERNDLLAQLVARPKCGFDMLRKIVFGANKE
  AYRFTIESERRKELKGCDTAAKLAKVNALGTRWQALSLDEQDRLVCLLLDGENDAVLADALREH
  YGLTDAQIDTLLGLSFEDGHMRLGRSALLRVLDALESGRDEQGLPLSYDKAVVAAGYPAHTADL
  ENGERDALPYYGELLWRYTQDAPTAKNDAERKFGKIANPTVHIGLNQLRKLVNALIQRYGKPAQ
  IVVELARNLKAGLEEKERIKKQQTANLERNERIRQKLQDAGVPDNRENRLRMRLFEELGQGNGL
  GTPCIYSGRQISLQRLFSNDVQVDHILPFSKTLDDSFANKVLAQHDANRYKGNRGPFEAFGANR
  DGYAWDDIRARAAVLPRNKRNRFAETAMQDWLHNETDFLARQLTDTAYLSRVARQYLTAICSKD
  DVYVSPGRLTAMLRAKWGLNRVLDGVMEEQGRPAVKNRDDHRHHAIDAVVIGATDRAMLQQVAT
  LAARAREQDAERLIGDMPTPWPNFLEDVRAAVARCVVSHKPDHGPEGGLHNDTAYGIVAGPFED
  GRYRVRHRVSLFDLKPGDLSNVRCDAPLQAELEPIFEQDDARAREVALTALAERYRQRKVWLEE
  LMSVLPIRPRGEDGKTLPDSAPYKAYKGDSNYCYELFINERGRWDGELISTFRANQAAYRRFRN
  DPARFRRYTAGGRPLLMRLCINDYIAVGTAAERTIFRVVKMSENKITLAEHFEGGTLKQRDADK
  DDPFKYLTKSPGALRDLGARRIFVDLIGRVLDPGIKGD
  SEQ ID NO: 383
  MIERILGVDLGISSLGWAIVEYDKDDEAANRIIDCGVRLFTAAETPKKKESPNKARREARGIRR
  VLNRRRVRMNMIKKLFLRAGLIQDVDLDGEGGMFYSKANRADVWELRHDGLYRLLKGDELARVL
  IHIAKHRGYKFIGDDEADEESGKVKKAGVVLRQNFEAAGCRTVGEWLWRERGANGKKRNKHGDY
  EISIHRDLLVEEVEAIFVAQQEMRSTIATDALKAAYREIAFFVRPMQRIEKMVGHCTYFPEERR
  APKSAPTAEKFIAISKFFSTVIIDNEGWEQKIIERKTLEELLDFAVSREKVEFRHLRKFLDLSD
  NEIFKGLHYKGKPKTAKKREATLFDPNEPTELEFDKVEAEKKAWISLRGAAKLREALGNEFYGR
  FVALGKHADEATKILTYYKDEGQKRRELTKLPLEAEMVERLVKIGFSDFLKLSLKAIRDILPAM
  ESGARYDEAVLMLGVPHKEKSAILPPLNKTDIDILNPTVIRAFAQFRKVANALVRKYGAFDRVH
  FELAREINTKGEIEDIKESQRKNEKERKEAADWIAETSFQVPLTRKNILKKRLYIQQDGRCAYT
  GDVIELERLFDEGYCEIDHILPRSRSADDSFANKVLCLARANQQKTDRTPYEWFGHDAARWNAF
  ETRTSAPSNRVRTGKGKIDRLLKKNFDENSEMAFKDRNLNDTRYMARAIKTYCEQYWVFKNSHT
  KAPVQVRSGKLTSVLRYQWGLESKDRESHTHHAVDAIIIAFSTQGMVQKLSEYYRFKETHREKE
  RPKLAVPLANFRDAVEEATRIENTETVKEGVEVKRLLISRPPRARVTGQAHEQTAKPYPRIKQV
  KNKKKWRLAPIDEEKFESFKADRVASANQKNFYETSTIPRVDVYHKKGKFHLVPIYLHEMVLNE
  LPNLSLGTNPEAMDENFFKFSIFKDDLISIQTQGTPKKPAKIIMGYFKNMHGANMVLSSINNSP
  CEGFTCTPVSMDKKHKDKCKLCPEENRIAGRCLQGFLDYWSQEGLRPPRKEFECDQGVKFALDV
  KKYQIDPLGYYYEVKQEKRLGTIPQMRSAKKLVKK
  SEQ ID NO: 384
  MNNSIKSKPEVTIGLDLGVGSVGWAIVDNETNIIHHLGSRLFSQAKTAEDRRSFRGVRRLIRRR
  KYKLKRFVNLIWKYNSYFGFKNKEDILNNYQEQQKLHNTVLNLKSEALNAKIDPKALSWILHDY
  LKNRGHFYEDNRDFNVYPTKELAKYFDKYGYYKGIIDSKEDNDNKLEEELTKYKFSNKHWLEEV
  KKVLSNQTGLPEKFKEEYESLFSYVRNYSEGPGSINSVSPYGIYHLDEKEGKVVQKYNNIWDKT
  IGKCNIFPDEYRAPKNSPIAMIFNEINELSTIRSYSIYLTGWFINQEFKKAYLNKLLDLLIKTN
  GEKPIDARQFKKLREETIAESIGKETLKDVENEEKLEKEDHKWKLKGLKLNTNGKIQYNDLSSL
  AKFVHKLKQHLKLDFLLEDQYATLDKINFLQSLFVYLGKHLRYSNRVDSANLKEFSDSNKLFER
  ILQKQKDGLFKLFEQTDKDDEKILAQTHSLSTKAMLLAITRMTNLDNDEDNQKNNDKGWNFEAI
  KNFDQKFIDITKKNNNLSLKQNKRYLDDRFINDAILSPGVKRILREATKVFNAILKQFSEEYDV
  TKVVIELARELSEEKELENTKNYKKLIKKNGDKISEGLKALGISEDEIKDILKSPTKSYKFLLW
  LQQDHIDPYSLKEIAFDDIFTKTEKFEIDHIIPYSISFDDSSSNKLLVLAESNQAKSNQTPYEF
  ISSGNAGIKWEDYEAYCRKFKDGDSSLLDSTQRSKKFAKMMKTDTSSKYDIGFLARNLNDTRYA
  TIVFRDALEDYANNHLVEDKPMFKVVCINGSVTSFLRKNFDDSSYAKKDRDKNIHHAVDASIIS
  IFSNETKTLFNQLTQFADYKLFKNTDGSWKKIDPKTGVVTEVTDENWKQIRVRNQVSEIAKVIE
  KYIQDSNIERKARYSRKIENKTNISLFNDTVYSAKKVGYEDQIKRKNLKTLDIHESAKENKNSK
  VKRQFVYRKLVNVSLLNNDKLADLFAEKEDILMYRANPWVINLAEQIFNEYTENKKIKSQNVFE
  KYMLDLTKEFPEKFSEFLVKSMLRNKTAIIYDDKKNIVHRIKRLKMLSSELKENKLSNVIIRSK
  NQSGTKLSYQDTINSLALMIMRSIDPTAKKQYIRVPLNTLNLHLGDHDFDLHNMDAYLKKPKFV
  KYLKANEIGDEYKPWRVLTSGTLLIHKKDKKLMYISSFQNLNDVIEIKNLIETEYKENDDSDSK
  KKKKANRFLMTLSTILNDYILLDAKDNFDILGLSKNRIDEILNSKLGLDKIVK
  SEQ ID NO: 385
  MGGSEVGTVPVTWRLGVDVGERSIGLAAVSYEEDKPKEILAAVSWIHDGGVGDERSGASRLALR
  GMARRARRLRRFRRARLRDLDMLLSELGWTPLPDKNVSPVDAWLARKRLAEEYVVDETERRRLL
  GYAVSHMARHRGWRNPWTTIKDLKNLPQPSDSWERTRESLEARYSVSLEPGTVGQWAGYLLQRA
  PGIRLNPTQQSAGRRAELSNATAFETRLRQEDVLWELRCIADVQGLPEDVVSNVIDAVFCQKRP
  SVPAERIGRDPLDPSQLRASRACLEFQEYRIVAAVANLRIRDGSGSRPLSLEERNAVIEALLAQ
  TERSLTWSDIALEILKLPNESDLTSVPEEDGPSSLAYSQFAPFDETSARIAEFIAKNRRKIPTF
  AQWWQEQDRTSRSDLVAALADNSIAGEEEQELLVHLPDAELEALEGLALPSGRVAYSRLTLSGL
  TRVMRDDGVDVHNARKTCFGVDDNWRPPLPALHEATGHPVVDRNLAILRKFLSSATMRWGPPQS
  IVVELARGASESRERQAEEEAARRAHRKANDRIRAELRASGLSDPSPADLVRARLLELYDCHCM
  YCGAPISWENSELDHIVPRTDGGSNRHENLAITCGACNKEKGRRPFASWAETSNRVQLRDVIDR
  VQKLKYSGNMYWTRDEFSRYKKSVVARLKRRTSDPEVIQSIESTGYAAVALRDRLLSYGEKNGV
  AQVAVFRGGVTAEARRWLDISIERLFSRVAIFAQSTSTKRLDRRHHAVDAVVLTTLTPGVAKTL
  ADARSRRVSAEFWRRPSDVNRHSTEEPQSPAYRQWKESCSGLGDLLISTAARDSIAVAAPLRLR
  PTGALHEETLRAFSEHTVGAAWKGAELRRIVEPEVYAAFLALTDPGGRFLKVSPSEDVLPADEN
  RHIVLSDRVLGPRDRVKLFPDDRGSIRVRGGAAYIASFHHARVFRWGSSHSPSFALLRVSLADL
  AVAGLLRDGVDVFTAELPPWTPAWRYASIALVKAVESGDAKQVGWLVPGDELDFGPEGVTTAAG
  DLSMFLKYFPERHWVVTGFEDDKRINLKPAFLSAEQAEVLRTERSDRPDTLTEAGEILAQFFPR
  CWRATVAKVLCHPGLTVIRRTALGQPRWRRGHLPYSWRPWSADPWSGGTP
  SEQ ID NO: 386
  MHNKKNITIGFDLGIASIGWAIIDSTTSKILDWGTRTFEERKTANERRAFRSTRRNIRRKAYRN
  QRFINLILKYKDLFELKNISDIQRANKKDTENYEKIISFFTEIYKKCAAKHSNILEVKVKALDS
  KIEKLDLIWILHDYLENRGFFYDLEEENVADKYEGIEHPSILLYDFFKKNGFFKSNSSIPKDLG
  GYSFSNLQWVNEIKKLFEVQEINPEFSEKFLNLFTSVRDYAKGPGSEHSASEYGIFQKDEKGKV
  FKKYDNIWDKTIGKCSFFVEENRSPVNYPSYEIFNLLNQLINLSTDLKTTNKKIWQLSSNDRNE
  LLDELLKVKEKAKIISISLKKNEIKKIILKDFGFEKSDIDDQDTIEGRKIIKEEPTTKLEVTKH
  LLATIYSHSSDSNWININNILEFLPYLDAICIILDREKSRGQDEVLKKLTEKNIFEVLKIDREK
  QLDFVKSIFSNTKFNFKKIGNFSLKAIREFLPKMFEQNKNSEYLKWKDEEIRRKWEEQKSKLGK
  TDKKTKYLNPRIFQDEIISPGTKNTFEQAVLVLNQIIKKYSKENIIDAIIIESPREKNDKKTIE
  EIKKRNKKGKGKTLEKLFQILNLENKGYKLSDLETKPAKLLDRLRFYHQQDGIDLYTLDKINID
  QLINGSQKYEIEHIIPYSMSYDNSQANKILTEKAENLKKGKLIASEYIKRNGDEFYNKYYEKAK
  ELFINKYKKNKKLDSYVDLDEDSAKNRFRFLTLQDYDEFQVEFLARNLNDTRYSTKLFYHALVE
  HFENNEFFTYIDENSSKHKVKISTIKGHVTKYFRAKPVQKNNGPNENLNNNKPEKIEKNRENNE
  HHAVDAAIVAIIGNKNPQIANLLTLADNKTDKKFLLHDENYKENIETGELVKIPKFEVDKLAKV
  EDLKKIIQEKYEEAKKHTAIKFSRKTRTILNGGLSDETLYGFKYDEKEDKYFKIIKKKLVTSKN
  EELKKYFENPFGKKADGKSEYTVLMAQSHLSEFNKLKEIFEKYNGFSNKTGNAFVEYMNDLALK
  EPTLKAEIESAKSVEKLLYYNFKPSDQFTYHDNINNKSFKRFYKNIRIIEYKSIPIKFKILSKH
  DGGKSFKDTLFSLYSLVYKVYENGKESYKSIPVTSQMRNFGIDEFDFLDENLYNKEKLDIYKSD
  FAKPIPVNCKPVFVLKKGSILKKKSLDIDDFKETKETEEGNYYFISTISKRFNRDTAYGLKPLK
  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.

• 	(SEQ ID NO: 22)
  	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
  	ATGATTAAAT 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 AGATTGTCAA 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 CAGTAGCAAA GAGGTCCTCG ATGCCACCCT
  	CATCCACCAG TCAATTACTG GCCTGTACGA AACACGGATC
  	GACCTCTCTC AACTGGGCGG CGAGTAG

• Provided below is the corresponding amino acid sequence of a S. pyogenes Cas9 molecule.

• (SEQ ID NO: 23)
  MDKKYSIGLDIGTNSVGWAVITDEYKVPSKKFKVLGNTDRHSIKKNLIGALLFDSGETAEATRL
  KRTARRRYTRRKNRICYLQEIFSNEMAKVDDSFFHRLEESFLVEEDKKHERHPIFGNIVDEVAY
  HEKYPTIYHLRKKLVDSTDKADLRLIYLALAHMIKFRGHFLIEGDLNPDNSDVDKLFIQLVQTY
  NQLFEENPINASGVDAKAILSARLSKSRRLENLIAQLPGEKKNGLFGNLIALSLGLTPNFKSNF
  DLAEDAKLQLSKDTYDDDLDNLLAQIGDQYADLFLAAKNLSDAILLSDILRVNTEITKAPLSAS
  MIKRYDEHHQDLTLLKALVRQQLPEKYKEIFFDQSKNGYAGYIDGGASQEEFYKFIKPILEKMD
  GTEELLVKLNREDLLRKQRTFDNGSIPHQIHLGELHAILRRQEDFYPFLKDNREKIEKILTFRI
  PYYVGPLARGNSRFAWMTRKSEETITPWNFEEVVDKGASAQSFIERMTNFDKNLPNEKVLPKHS
  LLYEYFTVYNELTKVKYVTEGMRKPAFLSGEQKKAIVDLLFKTNRKVTVKQLKEDYFKKIECFD
  SVEISGVEDRFNASLGTYHDLLKIIKDKDFLDNEENEDILEDIVLTLTLFEDREMIEERLKTYA
  HLFDDKVMKQLKRRRYTGWGRLSRKLINGIRDKQSGKTILDFLKSDGFANRNFMQLIHDDSLTF
  KEDIQKAQVSGQGDSLHEHIANLAGSPAIKKGILQTVKVVDELVKVMGRHKPENIVIEMARENQ
  TTQKGQKNSRERMKRIEEGIKELGSQILKEHPVENTQLQNEKLYLYYLQNGRDMYVDQELDINR
  LSDYDVDHIVPQSFLKDDSIDNKVLTRSDKNRGKSDNVPSEEVVKKMKNYWRQLLNAKLITQRK
  FDNLTKAERGGLSELDKAGFIKRQLVETRQITKHVAQILDSRMNTKYDENDKLIREVKVITLKS
  KLVSDFRKDFQFYKVREINNYHHAHDAYLNAVVGTALIKKYPKLESEFVYGDYKVYDVRKMIAK
  SEQEIGKATAKYFFYSNIMNFFKTEITLANGEIRKRPLIETNGETGEIVWDKGRDFATVRKVLS
  MPQVNIVKKTEVQTGGFSKESILPKRNSDKLIARKKDWDPKKYGGFDSPTVAYSVLVVAKVEKG
  KSKKLKSVKELLGITIMERSSFEKNPIDFLEAKGYKEVKKDLIIKLPKYSLFELENGRKRMLAS
  AGELQKGNELALPSKYVNFLYLASHYEKLKGSPEDNEQKQLFVEQHKHYLDEIIEQISEFSKRV
  ILADANLDKVLSAYNKHRDKPIREQAENIIHLFTLTNLGAPAAFKYFDTTIDRKRYTSTKEVLD
  ATLIHQSITGLYETRIDLSQLGGD*

• Provided below is an exemplary codon optimized nucleic acid sequence encoding a Cas9 molecule of N. meningitidis.

• (SEQ ID NO: 24)
  ATGGCCGCCTTCAAGCCCAACCCCATCAACTACATCCTGGGCCTGGACATCGGCATCGCCAGCG
  TGGGCTGGGCCATGGTGGAGATCGACGAGGACGAGAACCCCATCTGCCTGATCGACCTGGGTGT
  GCGCGTGTTCGAGCGCGCTGAGGTGCCCAAGACTGGTGACAGTCTGGCTATGGCTCGCCGGCTT
  GCTCGCTCTGTTCGGCGCCTTACTCGCCGGCGCGCTCACCGCCTTCTGCGCGCTCGCCGCCTGC
  TGAAGCGCGAGGGTGTGCTGCAGGCTGCCGACTTCGACGAGAACGGCCTGATCAAGAGCCTGCC
  CAACACTCCTTGGCAGCTGCGCGCTGCCGCTCTGGACCGCAAGCTGACTCCTCTGGAGTGGAGC
  GCCGTGCTGCTGCACCTGATCAAGCACCGCGGCTACCTGAGCCAGCGCAAGAACGAGGGCGAGA
  CCGCCGACAAGGAGCTGGGTGCTCTGCTGAAGGGCGTGGCCGACAACGCCCACGCCCTGCAGAC
  TGGTGACTTCCGCACTCCTGCTGAGCTGGCCCTGAACAAGTTCGAGAAGGAGAGCGGCCACATC
  CGCAACCAGCGCGGCGACTACAGCCACACCTTCAGCCGCAAGGACCTGCAGGCCGAGCTGATCC
  TGCTGTTCGAGAAGCAGAAGGAGTTCGGCAACCCCCACGTGAGCGGCGGCCTGAAGGAGGGCAT
  CGAGACCCTGCTGATGACCCAGCGCCCCGCCCTGAGCGGCGACGCCGTGCAGAAGATGCTGGGC
  CACTGCACCTTCGAGCCAGCCGAGCCCAAGGCCGCCAAGAACACCTACACCGCCGAGCGCTTCA
  TCTGGCTGACCAAGCTGAACAACCTGCGCATCCTGGAGCAGGGCAGCGAGCGCCCCCTGACCGA
  CACCGAGCGCGCCACCCTGATGGACGAGCCCTACCGCAAGAGCAAGCTGACCTACGCCCAGGCC
  CGCAAGCTGCTGGGTCTGGAGGACACCGCCTTCTTCAAGGGCCTGCGCTACGGCAAGGACAACG
  CCGAGGCCAGCACCCTGATGGAGATGAAGGCCTACCACGCCATCAGCCGCGCCCTGGAGAAGGA
  GGGCCTGAAGGACAAGAAGAGTCCTCTGAACCTGAGCCCCGAGCTGCAGGACGAGATCGGCACC
  GCCTTCAGCCTGTTCAAGACCGACGAGGACATCACCGGCCGCCTGAAGGACCGCATCCAGCCCG
  AGATCCTGGAGGCCCTGCTGAAGCACATCAGCTTCGACAAGTTCGTGCAGATCAGCCTGAAGGC
  CCTGCGCCGCATCGTGCCCCTGATGGAGCAGGGCAAGCGCTACGACGAGGCCTGCGCCGAGATC
  TACGGCGACCACTACGGCAAGAAGAACACCGAGGAGAAGATCTACCTGCCTCCTATCCCCGCCG
  ACGAGATCCGCAACCCCGTGGTGCTGCGCGCCCTGAGCCAGGCCCGCAAGGTGATCAACGGCGT
  GGTGCGCCGCTACGGCAGCCCCGCCCGCATCCACATCGAGACCGCCCGCGAGGTGGGCAAGAGC
  TTCAAGGACCGCAAGGAGATCGAGAAGCGCCAGGAGGAGAACCGCAAGGACCGCGAGAAGGCCG
  CCGCCAAGTTCCGCGAGTACTTCCCCAACTTCGTGGGCGAGCCCAAGAGCAAGGACATCCTGAA
  GCTGCGCCTGTACGAGCAGCAGCACGGCAAGTGCCTGTACAGCGGCAAGGAGATCAACCTGGGC
  CGCCTGAACGAGAAGGGCTACGTGGAGATCGACCACGCCCTGCCCTTCAGCCGCACCTGGGACG
  ACAGCTTCAACAACAAGGTGCTGGTGCTGGGCAGCGAGAACCAGAACAAGGGCAACCAGACCCC
  CTACGAGTACTTCAACGGCAAGGACAACAGCCGCGAGTGGCAGGAGTTCAAGGCCCGCGTGGAG
  ACCAGCCGCTTCCCCCGCAGCAAGAAGCAGCGCATCCTGCTGCAGAAGTTCGACGAGGACGGCT
  TCAAGGAGCGCAACCTGAACGACACCCGCTACGTGAACCGCTTCCTGTGCCAGTTCGTGGCCGA
  CCGCATGCGCCTGACCGGCAAGGGCAAGAAGCGCGTGTTCGCCAGCAACGGCCAGATCACCAAC
  CTGCTGCGCGGCTTCTGGGGCCTGCGCAAGGTGCGCGCCGAGAACGACCGCCACCACGCCCTGG
  ACGCCGTGGTGGTGGCCTGCAGCACCGTGGCCATGCAGCAGAAGATCACCCGCTTCGTGCGCTA
  CAAGGAGATGAACGCCTTCGACGGTAAAACCATCGACAAGGAGACCGGCGAGGTGCTGCACCAG
  AAGACCCACTTCCCCCAGCCCTGGGAGTTCTTCGCCCAGGAGGTGATGATCCGCGTGTTCGGCA
  AGCCCGACGGCAAGCCCGAGTTCGAGGAGGCCGACACCCCCGAGAAGCTGCGCACCCTGCTGGC
  CGAGAAGCTGAGCAGCCGCCCTGAGGCCGTGCACGAGTACGTGACTCCTCTGTTCGTGAGCCGC
  GCCCCCAACCGCAAGATGAGCGGTCAGGGTCACATGGAGACCGTGAAGAGCGCCAAGCGCCTGG
  ACGAGGGCGTGAGCGTGCTGCGCGTGCCCCTGACCCAGCTGAAGCTGAAGGACCTGGAGAAGAT
  GGTGAACCGCGAGCGCGAGCCCAAGCTGTACGAGGCCCTGAAGGCCCGCCTGGAGGCCCACAAG
  GACGACCCCGCCAAGGCCTTCGCCGAGCCCTTCTACAAGTACGACAAGGCCGGCAACCGCACCC
  AGCAGGTGAAGGCCGTGCGCGTGGAGCAGGTGCAGAAGACCGGCGTGTGGGTGCGCAACCACAA
  CGGCATCGCCGACAACGCCACCATGGTGCGCGTGGACGTGTTCGAGAAGGGCGACAAGTACTAC
  CTGGTGCCCATCTACAGCTGGCAGGTGGCCAAGGGCATCCTGCCCGACCGCGCCGTGGTGCAGG
  GCAAGGACGAGGAGGACTGGCAGCTGATCGACGACAGCTTCAACTTCAAGTTCAGCCTGCACCC
  CAACGACCTGGTGGAGGTGATCACCAAGAAGGCCCGCATGTTCGGCTACTTCGCCAGCTGCCAC
  CGCGGCACCGGCAACATCAACATCCGCATCCACGACCTGGACCACAAGATCGGCAAGAACGGCA
  TCCTGGAGGGCATCGGCGTGAAGACCGCCCTGAGCTTCCAGAAGTACCAGATCGACGAGCTGGG
  CAAGGAGATCCGCCCCTGCCGCCTGAAGAAGCGCCCTCCTGTGCGCTAA

• Provided below is the corresponding amino acid sequence of a N. meningitidis Cas9 molecule.

• (SEQ ID NO: 25)
  MAAFKPNPINYILGLDIGIASVGWAMVEIDEDENPICLIDLGVRVFERAEVPKTGDSLAMARRL
  ARSVRRLTRRRAHRLLRARRLLKREGVLQAADFDENGLIKSLPNTPWQLRAAALDRKLTPLEWS
  AVLLHLIKHRGYLSQRKNEGETADKELGALLKGVADNAHALQTGDFRTPAELALNKFEKESGHI
  RNQRGDYSHTFSRKDLQAELILLFEKQKEFGNPHVSGGLKEGIETLLMTQRPALSGDAVQKMLG
  HCTFEPAEPKAAKNTYTAERFIWLTKLNNLRILEQGSERPLTDTERATLMDEPYRKSKLTYAQA
  RKLLGLEDTAFFKGLRYGKDNAEASTLMEMKAYHAISRALEKEGLKDKKSPLNLSPELQDEIGT
  AFSLFKTDEDITGRLKDRIQPEILEALLKHISFDKFVQISLKALRRIVPLMEQGKRYDEACAEI
  YGDHYGKKNTEEKIYLPPIPADEIRNPVVLRALSQARKVINGVVRRYGSPARIHIETAREVGKS
  FKDRKEIEKRQEENRKDREKAAAKFREYFPNFVGEPKSKDILKLRLYEQQHGKCLYSGKEINLG
  RLNEKGYVEIDHALPFSRTWDDSFNNKVLVLGSENQNKGNQTPYEYFNGKDNSREWQEFKARVE
  TSRFPRSKKQRILLQKFDEDGFKERNLNDTRYVNRFLCQFVADRMRLTGKGKKRVFASNGQITN
  LLRGFWGLRKVRAENDRHHALDAVVVACSTVAMQQKITRFVRYKEMNAFDGKTIDKETGEVLHQ
  KTHFPQPWEFFAQEVMIRVFGKPDGKPEFEEADTPEKLRTLLAEKLSSRPEAVHEYVTPLFVSR
  APNRKMSGQGHMETVKSAKRLDEGVSVLRVPLTQLKLKDLEKMVNREREPKLYEALKARLEAHK
  DDPAKAFAEPFYKYDKAGNRTQQVKAVRVEQVQKTGVWVRNHNGIADNATMVRVDVFEKGDKYY
  LVPIYSWQVAKGILPDRAVVQGKDEEDWQLIDDSFNFKFSLHPNDLVEVITKKARMFGYFASCH
  RGTGNINIRIHDLDHKIGKNGILEGIGVKTALSFQKYQIDELGKEIRPCRLKKRPPVR*

• Provided below is an amino acid sequence of a S. aureus Cas9 molecule.

• (SEQ ID NO: 26)
  MKRNYILGLDIGITSVGYGIIDYETRDVIDAGVRLFKEANVENNEGRRSKRGARRLKRRRRHRI
  QRVKKLLFDYNLLTDHSELSGINPYEARVKGLSQKLSEEEFSAALLHLAKRRGVHNVNEVEEDT
  GNELSTKEQISRNSKALEEKYVAELQLERLKKDGEVRGSINRFKTSDYVKEAKQLLKVQKAYHQ
  LDQSFIDTYIDLLETRRTYYEGPGEGSPFGWKDIKEWYEMLMGHCTYFPEELRSVKYAYNADLY
  NALNDLNNLVITRDENEKLEYYEKFQIIENVFKQKKKPTLKQIAKEILVNEEDIKGYRVTSTGK
  PEFTNLKVYHDIKDITARKEIIENAELLDQIAKILTIYQSSEDIQEELTNLNSELTQEEIEQIS
  NLKGYTGTHNLSLKAINLILDELWHTNDNQIAIFNRLKLVPKKVDLSQQKEIPTTLVDDFILSP
  VVKRSFIQSIKVINAIIKKYGLPNDIIIELAREKNSKDAQKMINEMQKRNRQTNERIEEIIRTT
  GKENAKYLIEKIKLHDMQEGKCLYSLEAIPLEDLLNNPFNYEVDHIIPRSVSFDNSFNNKVLVK
  QEENSKKGNRTPFQYLSSSDSKISYETFKKHILNLAKGKGRISKTKKEYLLEERDINRFSVQKD
  FINRNLVDTRYATRGLMNLLRSYFRVNNLDVKVKSINGGFTSFLRRKWKFKKERNKGYKHHAED
  ALIIANADFIFKEWKKLDKAKKVMENQMFEEKQAESMPEIETEQEYKEIFITPHQIKHIKDFKD
  YKYSHRVDKKPNRELINDTLYSTRKDDKGNTLIVNNLNGLYDKDNDKLKKLINKSPEKLLMYHH
  DPQTYQKLKLIMEQYGDEKNPLYKYYEETGNYLTKYSKKDNGPVIKKIKYYGNKLNAHLDITDD
  YPNSRNKVVKLSLKPYRFDVYLDNGVYKFVTVKNLDVIKKENYYEVNSKCYEEAKKLKKISNOA
  EFIASEYNNDLIKINGELYRVIGVNNDLLNRIEVNMIDITYREYLENMNDKRPPRIIKTIASKT
  QSIKKYSTDILGNLYEVKSKKHPQIIKKG*

• Provided below is an exemplary codon optimized nucleic acid sequence encoding a Cas9 molecule of S. aureus Cas9.

• (SEQ ID NO: 39)
  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

• 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 33.

• TABLE 33
  Cas Systems

  			Structure of	Families (and
  			encoded	superfamily)
  			protein	of
  Gene	System type	Name from	(PDB	encoded
  name‡	or subtype	Haft et al.§	accessions)¶	protein#**	Representatives
  cas1	Type I	cas1	3GOD, 3LFX	COG1518	SERP2463, SPy1047
  	Type II		and 2YZS		and ygbT
  	Type III
  cas2	Type I	cas2	2IVY, 2I8E and	COG1343 and	SERP2462, SPy1048,
  	Type II		3EXC	COG3512	SPy1723 (N-terminal
  	Type III				domain) and ygbF
  cas3′	Type I‡‡	cas3	NA	COG1203	APE1232 and ygcB
  cas3″	Subtype I-A	NA	NA	COG2254	APE1231 and BH0336
  	Subtype I-B
  cas4	Subtype I-A	cas4 and csa1	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 ygcI
  	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-A
  	Subtype
  	III-B
  cas6e	Subtype I-E	cse3	1WJ9	(RAMP)	ygcH
  cas6f	Subtype I-F	csy4	2XLJ	(RAMP)	y1727
  cas7	Subtype I-A	csa2, csd2,	NA	COG1857 and	devR and ygcJ
  	Subtype I-B	cse4, csh2,		COG3649
  	Subtype I-C	csp1 and cst2		(RAMP)
  	Subtype I-E
  cas8a1	Subtype I-	cmx1, cst1,	NA	BH0338-like	LA3191§§ and
  	A‡‡	csx8, csx13			PG2018§§
  		and CXXC-
  		CXXC
  cas8a2	Subtype I-	csa4 and csx9	NA	PH0918	AF0070, AF1873,
  	A‡‡				MJ0385, PF0637,
  					PH0918 and SSO1401
  cas8b	Subtype I-	csh1 and	NA	BH0338-like	MTH1090 and
  	B‡‡	TM1802			TM1802
  cas8c	Subtype I-	csd1 and csp2	NA	BH0338-like	BH0338
  	C‡‡
  cas9	Type II‡‡	csn1 and csx12	NA	COG3513	FTN_0757 and
  					SPy1046
  cas10	Type III‡‡	cmr2, csm1	NA	COG1353	MTH326, Rv2823c§§
  		and csx111			and TM1794§§
  cas10d	Subtype I-	csc3	NA	COG1353	slr7011
  	D‡‡
  csy1	Subtype I-	csy1	NA	y1724-like	y1724
  	F‡‡
  csy2	Subtype I-F	csy2	NA	(RAMP)	y1725
  csy3	Subtype I-F	csy3	NA	(RAMP)	y1726
  cse1	Subtype I-	cse1	NA	YgcL-like	ygcL
  	E‡‡
  cse2	Subtype I-E	cse2	2ZCA	YgcK-like	ygcK
  csc1	Subtype I-D	csc1	NA	alr1563-like	alr1563
  				(RAMP)
  csc2	Subtype I-D	csc1 and csc2	NA	COG1337	slr7012
  				(RAMP)
  csa5	Subtype I-A	csa5	NA	AF1870	AF1870, MJ0380,
  					PF0643 and SSO1398
  csn2	Subtype II-	csn2	NA	SPy1049-like	SPy1049
  	A
  csm2	Subtype III-	csm2	NA	COG1421	MTH1081 and
  	A‡‡				SERP2460
  csm3	Subtype III-	csc2 and csm3	NA	COG1337	MTH1080 and
  	A			(RAMP)	SERP2459
  csm4	Subtype III-	csm4	NA	COG1567	MTH1079 and
  	A			(RAMP)	SERP2458
  csm5	Subtype III-	csm5	NA	COG1332	MTH1078 and
  	A			(RAMP)	SERP2457
  csm6	Subtype III-	APE2256 and	2WTE	COG1517	APE2256 and
  	A	csm6			SSO1445
  cmr1	Subtype III-	cmr1	NA	COG1367	PF1130
  	B			(RAMP)
  cmr3	Subtype III-	cmr3	NA	COG1769	PF1128
  	B			(RAMP)
  cmr4	Subtype III-	cmr4	NA	COG1336	PF1126
  	B			(RAMP)
  cmr5	Subtype III-	cmr5	2ZOP and 2OEB	COG3337	MTH324 and PF1125
  	B‡‡
  cmr6	Subtype III-	cmr6	NA	COG1604	PF1124
  	B			(RAMP)
  csb1	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§§
  csx17	Subtype I-U	NA	NA	NA	Btus_2683
  csx14	Subtype I-U	NA	NA	NA	GSU0052
  csx10	Subtype I-U	csx10	NA	(RAMP)	Caur_2274
  csx16	Subtype III-	VVA1548	NA	NA	VVA1548
  	U
  csaX	Subtype III-	csaX	NA	NA	SSO1438
  	U
  csx3	Subtype III-	csx3	NA	NA	AF1864
  	U
  csx1	Subtype III-	csa3, csx1,	1XMX and 2171	COG1517 and	MJ1666, NE0113,
  	U	csx2, DXTHG,		COG4006	PF1127 andTM1812
  		NE0113 and
  		TIGR02710
  csx15	Unknown	NA	NA	TTE2665	TTE2665
  csf1	Type U	csf1	NA	NA	AFE_1038
  csf2	Type U	csf2	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 KCl, 0.5 mM DTT, 0.1 mM EDTA) with or without 10 mM MgCl₂. The reactions are stopped with 5×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-32P]-ATP in 1×T4 polynucleotide kinase reaction buffer at 37° C. for 30 min, in a 50 μL 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 KCl, 5 mM MgCl₂, 1 mM DTT, 5% glycerol) in a total volume of 9 μl. Reactions are initiated by the addition of 1 μl target DNA (10 nM) and incubated for 1 h at 37° C. Reactions are quenched by the addition of 20 μl 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 1×TBE. DNA bands are visualized by UV shadowing, excised, and eluted by soaking gel pieces in DEPC-treated H₂O. Eluted DNA is ethanol precipitated and dissolved in DEPC-treated H₂O. DNA samples are 5′ end labeled with [7-32P]-ATP 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 KCl, 5 mM MgCl₂, 1 mM DTT and 10% glycerol in a total volume of 10 μl. Cas9 protein molecule is programmed with equimolar amounts of pre-annealed gRNA molecule and titrated from 100 pM to 1 μM. 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 1×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 2 uM solution of Cas9 in water+10×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 10′ and brief centrifugation to remove any bubbles, a Bio-Rad CFX384™ Real-Time System C1000 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 2 uM 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+10×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 C1000 Touch™ Thermal Cycler with the Bio-Rad CFX Manager software is used to run a gradient from 20° C. to 90° C. with a 1° increase in temperature every 10 seconds.
V. Genome Editing Approaches
• Mutations in the HBB gene may be corrected using one of the approaches discussed herein. In an embodiment, a mutation in the HBB gene is corrected by homology directed repair (HDR) using an exogenously provided template nucleic acid (see Section V.1). In another embodiment, a mutation in the HBB gene is corrected by homology directed repair without using an exogenously provided template nucleic acid (see Section V.1).
• Also described herein are methods for targeted knockout of one or both alleles of the BCL11A gene using NHEJ (see Section V.2). In another embodiment, methods are provided for targeted knockdown of the BCL11A gene (see Section V.3).
V.1 HDR Repair and Template Nucleic Acids
• As described herein, nuclease-induced homology directed repair (HDR) can be used to alter a target sequence and correct (e.g., repair or edit) a mutation in the genome. While not wishing to be bound by theory, it is believed that alteration of the target sequence occurs by homology-directed repair (HDR) with an exogenously provided donor template or template nucleic acid. For example, the donor template or the template nucleic acid provides for alteration of the target sequence. It is contemplated that a plasmid donor can be used as a template for homologous recombination. It is further contemplated that a single stranded donor template can be used as a template for alteration of the target sequence by alternate methods of homology directed repair (e.g., single strand annealing) between the target sequence and the donor template. Donor template-effected alteration of a target sequence depends on cleavage by a Cas9 molecule. Cleavage by Cas9 can comprise a double strand break or two single strand breaks. As described herein, nuclease-induced homology directed repair (HDR) can be used to alter a target sequence and correct (e.g., repair or edit) a mutation in the genome without the use of an exogenously provided donor template or template nucleic acid. While not wishing to be bound by theory, it is believed that alteration of the target sequence occurs by homology-directed repair (HDR) with endogenous genomic donor sequence. For example, the endogenous genomic donor sequence provides for alteration of the target sequence. It is contemplated that in an embodiment the endogenous genomic donor sequence is located on the same chromosome as the target sequence. It is further contemplated that in another embodiment the endogenous genomic donor sequence is located on a different chromosome from the target sequence. In an embodiment, the endogenous genomic donor sequence comprises one or more nucleotides derived from the HBD gene. Alteration of a target sequence by endogenous genomic donor sequence depends on cleavage by a Cas9 molecule. Cleavage by Cas9 can comprise a double strand break or two single strand breaks.
• Mutations that can be corrected by HDR using a template nucleic acid, or using endogenous genomic donor sequence, include point mutations. In an embodiment, a point mutation can be corrected by either a single double-strand break or two single strand breaks. In an embodiment, a point mutation can be corrected by (1) a single double-strand break, (2) two single strand breaks, (3) two double stranded breaks with a break occurring on each side of the target position, (4) one double stranded break and two single strand breaks with the double strand break and two single strand breaks occurring on each side of the target position (5) four single stranded breaks with a pair of single stranded breaks occurring on each side of the target position, or (6) one single stranded break.
• In an embodiment where a single-stranded template nucleic acid is used, the target position can be altered by alternative HDR.
• Donor template-effected alteration of a target position depends on cleavage by a Cas9 molecule. Cleavage by Cas9 can comprise a nick, a double strand break, or two single strand breaks, e.g., one on each strand of the target nucleic acid. After introduction of the breaks on the target nucleic acid, resection occurs at the break ends resulting in single stranded overhanging DNA regions.
• In canonical HDR, a double-stranded donor template is introduced, comprising homologous sequence to the target nucleic acid that will either be directly incorporated into the target nucleic acid or used as a template to correct the sequence of the target nucleic acid. After resection at the break, repair can progress by different pathways, e.g., by the double Holliday junction model (or double strand break repair, DSBR, pathway) or the synthesis-dependent strand annealing (SDSA) pathway. In the double Holliday junction model, strand invasion by the two single stranded overhangs of the target nucleic acid to the homologous sequences in the donor template occurs, resulting in the formation of an intermediate with two Holliday junctions. The junctions migrate as new DNA is synthesized from the ends of the invading strand to fill the gap resulting from the resection. The end of the newly synthesized DNA is ligated to the resected end, and the junctions are resolved, resulting in the correction of the target nucleic acid, e.g., incorporation of the correct sequence of the donor template at the corresponding target position. Crossover with the donor template may occur upon resolution of the junctions. In the SDSA pathway, only one single stranded overhang invades the donor template and new DNA is synthesized from the end of the invading strand to fill the gap resulting from resection. The newly synthesized DNA then anneals to the remaining single stranded overhang, new DNA is synthesized to fill in the gap, and the strands are ligated to produce the corrected DNA duplex.
• In alternative HDR, a single strand donor template, e.g., template nucleic acid, is introduced. A nick, single strand break, or double strand break at the target nucleic acid, for altering a desired target position, is mediated by a Cas9 molecule, e.g., described herein, and resection at the break occurs to reveal single stranded overhangs. Incorporation of the sequence of the template nucleic acid to correct or alter the target position of the target nucleic acid typically occurs by the SDSA pathway, as described above.
• Methods of promoting HDR pathways, e.g., canonical HDR or alt-HDR, are described herein in Section VI.
• Additional details on template nucleic acids are provided in Section IV entitled “Template nucleic acids” in International Application PCT/US2014/057905.
• Mutations in the HBB gene that can be corrected (e.g., altered) by HDR with a template nucleic acid or with endogenous genomic donor sequence include, e.g., point mutation at E6, e.g., E6V.
• Double Strand Break Mediated Correction
• In an embodiment, double strand cleavage is effected by a Cas9 molecule having cleavage activity associated with an HNH-like domain and cleavage activity associated with a RuvC-like domain, e.g., an N-terminal RuvC-like domain, e.g., a wild type Cas9. Such embodiments require only a single gRNA.
• Single Strand Break Mediated Correction
• In some embodiments, one single strand break, or nick, is effected by a Cas9 molecule having nickase activity, e.g., a Cas9 nickase as described herein. A nicked target nucleic acid can be a substrate for alt-HDR.
• In other embodiments, two single strand breaks, or nicks, are effected by a Cas9 molecule having nickase activity, e.g., cleavage activity associated with an HNH-like domain or cleavage activity associated with an N-terminal RuvC-like domain. Such embodiments usually require two gRNAs, one for placement of each single strand break. In an embodiment, the Cas9 molecule having nickase activity cleaves the strand to which the gRNA hybridizes, but not the strand that is complementary to the strand to which the gRNA hybridizes. In an embodiment, the Cas9 molecule having nickase activity does not cleave the strand to which the gRNA hybridizes, but rather cleaves the strand that is complementary to the strand to which the gRNA hybridizes.
• In an embodiment, the nickase has HNH activity, e.g., a Cas9 molecule having the RuvC activity inactivated, e.g., a Cas9 molecule having a mutation at D10, e.g., the D10A mutation. D10A inactivates RuvC; therefore, the Cas9 nickase has (only) HNH activity and will cut on the strand to which the gRNA hybridizes (e.g., the complementary strand, which does not have the NGG PAM on it). In other embodiments, a Cas9 molecule having an H840, e.g., an H840A, mutation can be used as a nickase. H840A inactivates HNH; therefore, the Cas9 nickase has (only) RuvC activity and cuts on the non-complementary strand (e.g., the strand that has the NGG PAM and whose sequence is identical to the gRNA). In other embodiments, a Cas9 molecule having an N863 mutation, e.g., the N863A mutation, mutation can be used as a nickase. N863A inactivates HNH therefore the Cas9 nickase has (only) RuvC activity and cuts on the non-complementary strand (the strand that has the NGG PAM and whose sequence is identical to the gRNA).
• In an embodiment, in which a nickase and two gRNAs are used to position two single strand nicks, one nick is on the + strand and one nick is on the − strand of the target nucleic acid. The PAMs can be outwardly facing. The gRNAs can be selected such that the gRNAs are separated by, from about 0-50, 0-100, or 0-200 nucleotides. In an embodiment, there is no overlap between the target sequences that are complementary to the targeting domains of the two gRNAs. In an embodiment, the gRNAs do not overlap and are separated by as much as 50, 100, or 200 nucleotides. In an embodiment, the use of two gRNAs can increase specificity, e.g., by decreasing off-target binding (Ran et al., Cell 2013; 154(6):1380-1389).
• In an embodiment, a single nick can be used to induce HDR, e.g., alt-HDR. It is contemplated herein that a single nick can be used to increase the ratio of HR to NHEJ at a given cleavage site. 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.
• Placement of Double Strand or Single Strand Breaks Relative to the Target Position
• The double strand break or single strand break in one of the strands should be sufficiently close to target position such that an alteration is produced in the desired region, e.g., correction of a mutation occurs. In an embodiment, the distance is not more than 50, 100, 200, 300, 350 or 400 nucleotides. While not wishing to be bound by theory, in some embodiments, it is believed that the break should be sufficiently close to target position such that the target position is within the region that is subject to exonuclease-mediated removal during end resection. If the distance between the target position and a break is too great, the mutation or other sequence desired to be altered may not be included in the end resection and, therefore, may not be corrected, as donor sequence, either exogenously provided donor sequence or endogenous genomic donor sequence, in some embodiments is only used to correct sequence within the end resection region.
• In an embodiment, the targeting domain is configured such that a cleavage event, e.g., a double strand or single strand break, is positioned within 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150 or 200 nucleotides of the region desired to be altered, e.g., a mutation. The break, e.g., a double strand or single strand break, can be positioned upstream or downstream of the region desired to be altered, e.g., a mutation. In some embodiments, a break is positioned within the region desired to be altered, e.g., within a region defined by at least two mutant nucleotides. In some embodiments, a break is positioned immediately adjacent to the region desired to be altered, e.g., immediately upstream or downstream of a mutation. 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 bind configured such that a cleavage event, e.g., the two single strand breaks, are positioned within 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150 or 200 nucleotides of a target position. 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 desired region. 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, in which a gRNA (unimolecular (or chimeric) or modular gRNA) and Cas9 nuclease induce a double strand break for the purpose of inducing HDR-mediated correction, the cleavage site is between 0-200 bp (e.g., 0-175, 0 to 150, 0 to 125, 0 to 100, 0 to 75, 0 to 50, 0 to 25, 25 to 200, 25 to 175, 25 to 150, 25 to 125, 25 to 100, 25 to 75, 25 to 50, 50 to 200, 50 to 175, 50 to 150, 50 to 125, 50 to 100, 50 to 75, 75 to 200, 75 to 175, 75 to 150, 75 to 125, 75 to 100 bp) away from the target position. In an embodiment, the cleavage site is between 0-100 bp (e.g., 0 to 75, 0 to 50, 0 to 25, 25 to 100, 25 to 75, 25 to 50, 50 to 100, 50 to 75 or 75 to 100 bp) away from the target position.
• In embodiments, one can promote HDR by using nickases to generate a break with overhangs. While not wishing to be bound by theory, the single stranded nature of the overhangs can enhance the cell's likelihood of repairing the break by HDR as opposed to, e.g., NHEJ. Specifically, in some embodiments, HDR is promoted by selecting a first gRNA that targets a first nickase to a first target sequence, and a second gRNA that targets a second nickase to a second target sequence which is on the opposite DNA strand from the first target sequence and offset from the first nick.
• 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.
• Placement of a First Break and a Second Break Relative to Each Other
• 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.
• 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.
• 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.
• 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 stranded breaks, a single Cas9 nuclease may be used to create both double stranded breaks. When two or more gRNAs are used to position two or more single stranded breaks (nicks), a single Cas9 nickase may be used to create the two or more nicks. When two or more gRNAs are used to position at least one double stranded break and at least one single stranded break, two Cas9 proteins may be used, e.g., one Cas9 nuclease and one Cas9 nickase. It is contemplated that when two or more Cas9 proteins are used that the two or more Cas9 proteins may be delivered sequentially to control specificity of a double stranded versus a single stranded break at the desired position in the target nucleic acid.
• In some embodiments, the targeting domain of the first gRNA molecule and the targeting domain of the second gRNA molecules are complementary to opposite strands of the target nucleic acid molecule. In some embodiments, the gRNA molecule and the second gRNA molecule are configured such that the PAMs are oriented outward.
• In certain embodiments, two gRNA are selected to direct Cas9-mediated cleavage at two positions that are a preselected distance from each other. In embodiments, the two points of cleavage are on opposite strands of the target nucleic acid. In some embodiments, the two cleavage points form a blunt ended break, and in other embodiments, they are offset so that the DNA ends comprise one or two overhangs (e.g., one or more 5′ overhangs and/or one or more 3′ overhangs). In some embodiments, each cleavage event is a nick. In embodiments, the nicks are close enough together that they form a break that is recognized by the double stranded break machinery (as opposed to being recognized by, e.g., the SSBr machinery). In embodiments, the nicks are far enough apart that they create an overhang that is a substrate for HDR, i.e., the placement of the breaks mimics a DNA substrate that has experienced some resection. For instance, in some embodiments the nicks are spaced to create an overhang that is a substrate for processive resection. In some embodiments, the two breaks are spaced within 25-65 nucleotides of each other. The two breaks may be, e.g., about 25, 30, 35, 40, 45, 50, 55, 60 or 65 nucleotides of each other. The two breaks may be, e.g., at least about 25, 30, 35, 40, 45, 50, 55, 60 or 65 nucleotides of each other. The two breaks may be, e.g., at most about 30, 35, 40, 45, 50, 55, 60 or 65 nucleotides of each other. In embodiments, the two breaks are about 25-30, 30-35, 35-40, 40-45, 45-50, 50-55, 55-60, or 60-65 nucleotides of each other.
• In some embodiments, the break that mimics a resected break comprises a 3′ overhang (e.g., generated by a DSB and a nick, where the nick leaves a 3′ overhang), a 5′ overhang (e.g., generated by a DSB and a nick, where the nick leaves a 5′ overhang), a 3′ and a 5′ overhang (e.g., generated by three cuts), two 3′ overhangs (e.g., generated by two nicks that are offset from each other), or two 5′ overhangs (e.g., generated by two nicks that are offset from each other).
• In an embodiment, in which two gRNAs (independently, unimolecular (or chimeric) or modular gRNA) complexing with Cas9 nickases induce two single strand breaks for the purpose of inducing HDR-mediated correction, the closer nick is between 0-200 bp (e.g., 0-175, 0 to 150, 0 to 125, 0 to 100, 0 to 75, 0 to 50, 0 to 25, 25 to 200, 25 to 175, 25 to 150, 25 to 125, 25 to 100, 25 to 75, 25 to 50, 50 to 200, 50 to 175, 50 to 150, 50 to 125, 50 to 100, 50 to 75, 75 to 200, 75 to 175, 75 to 150, 75 to 125, 75 to 100 bp) away from the target position and the two nicks will ideally be within 25-65 bp of each other (e.g., 25 to 50, 25 to 45, 25 to 40, 25 to 35, 25 to 30, 30 to 55, 30 to 50, 30 to 45, 30 to 40, 30 to 35, 35 to 55, 35 to 50, 35 to 45, 35 to 40, 40 to 55, 40 to 50, 40 to 45 bp, 45 to 50 bp, 50 to 55 bp, 55 to 60 bp, 60 to 65 bp) and no more than 100 bp away from each other (e.g., no more than 90, 80, 70, 60, 50, 40, 30, 20, 10 or 5 bp away from each other). In an embodiment, the cleavage site is between 0-100 bp (e.g., 0 to 75, 0 to 50, 0 to 25, 25 to 100, 25 to 75, 25 to 50, 50 to 100, 50 to 75 or 75 to 100 bp) away from the target position.
• In one embodiment, two gRNAs, e.g., independently, unimolecular (or chimeric) or modular gRNA, are configured to position a double-strand break on both sides of a target position. In an alternate embodiment, three gRNAs, e.g., independently, unimolecular (or chimeric) or modular gRNA, are configured to position a double strand break (i.e., one gRNA complexes with a cas9 nuclease) and two single strand breaks or paired single stranded breaks (i.e., two gRNAs complex with Cas9 nickases) on either side of the target position. In another embodiment, four gRNAs, e.g., independently, unimolecular (or chimeric) or modular gRNA, are configured to generate two pairs of single stranded breaks (i.e., two pairs of two gRNAs complex with Cas9 nickases) on either side of the target position. The double strand break(s) or the closer of the two single strand nicks in a pair will ideally be within 0-500 bp of the target position (e.g., no more than 450, 400, 350, 300, 250, 200, 150, 100, 50 or 25 bp from the target position). When nickases are used, the two nicks in a pair are, in embodiments, within 25-65 bp of each other (e.g., between 25 to 55, 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, 40 to 45 bp, 45 to 50 bp, 50 to 55 bp, 55 to 60 bp, or 60 to 65 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).
• When two gRNAs are used to target Cas9 molecules to breaks, different combinations of Cas9 molecules are envisioned. In some embodiments, a first gRNA is used to target a first Cas9 molecule to a first target position, and a second gRNA is used to target a second Cas9 molecule to a second target position. In some embodiments, the first Cas9 molecule creates a nick on the first strand of the target nucleic acid, and the second Cas9 molecule creates a nick on the opposite strand, resulting in a double stranded break (e.g., a blunt ended cut or a cut with overhangs).
• Different combinations of nickases can be chosen to target one single stranded break to one strand and a second single stranded break to the opposite strand. When choosing a combination, one can take into account that there are nickases having one active RuvC-like domain, and nickases having one active HNH domain. In an embodiment, a RuvC-like domain cleaves the non-complementary strand of the target nucleic acid molecule. 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. Generally, if both Cas9 molecules have the same active domain (e.g., both have an active RuvC domain or both have an active HNH domain), one will choose two gRNAs that bind to opposite strands of the target. In more detail, in some embodiments, a first gRNA is complementary with a first strand of the target nucleic acid and binds a nickase having an active RuvC-like domain and causes that nickase to cleave the strand that is non-complementary to that first gRNA, i.e., a second strand of the target nucleic acid; and a second gRNA is complementary with a second strand of the target nucleic acid and binds a nickase having an active RuvC-like domain and causes that nickase to cleave the strand that is non-complementary to that second gRNA, i.e., the first strand of the target nucleic acid. Conversely, in some embodiments, a first gRNA is complementary with a first strand of the target nucleic acid and binds a nickase having an active HNH domain and causes that nickase to cleave the strand that is complementary to that first gRNA, i.e., a first strand of the target nucleic acid; and a second gRNA is complementary with a second strand of the target nucleic acid and binds a nickase having an active HNH domain and causes that nickase to cleave the strand that is complementary to that second gRNA, i.e., the second strand of the target nucleic acid. In another arrangement, if one Cas9 molecule has an active RuvC-like domain and the other Cas9 molecule has an active HNH domain, the gRNAs for both Cas9 molecules can be complementary to the same strand of the target nucleic acid, so that the Cas9 molecule with the active RuvC-like domain will cleave the non-complementary strand and the Cas9 molecule with the HNH domain will cleave the complementary strand, resulting in a double stranded break.
Length of the Homology Arms of the Donor Template
• The homology arm should extend at least as far as the region in which end resection may occur, e.g., in order to allow the resected single stranded overhang to find a complementary region within the donor template. The overall length could be limited by parameters such as plasmid size or viral packaging limits. In an embodiment, a homology arm does not extend into repeated elements, e.g., Alu repeats or LINE repeats.
• Exemplary homology arm lengths include at least 50, 100, 250, 500, 750, 1000, 2000, 3000, 4000, or 5000 nucleotides. In some embodiments, the homology arm length is 50-100, 100-250, 250-500, 500-750, 750-1000, 1000-2000, 2000-3000, 3000-4000, or 4000-5000 nucleotides.
• Target position, as used herein, refers to a site on a target nucleic acid (e.g., the chromosome) that is modified by a Cas9 molecule-dependent process. For example, the target position can be a modified Cas9 molecule cleavage of the target nucleic acid and template nucleic acid directed modification, e.g., correction, of the target position. In an embodiment, a target position can be a site between two nucleotides, e.g., adjacent nucleotides, on the target nucleic acid into which one or more nucleotides is added. The target position may comprise one or more nucleotides that are altered, e.g., corrected, by a template nucleic acid. In an embodiment, the target position is within a target sequence (e.g., the sequence to which the gRNA binds). In an embodiment, a target position is upstream or downstream of a target sequence (e.g., the sequence to which the gRNA binds).
• A template nucleic acid, as that term is used herein, refers to a nucleic acid sequence which can be used in conjunction with a Cas9 molecule and a gRNA molecule to alter the structure of a target position. In an embodiment, the target nucleic acid is modified to have the some or all of the sequence of the template nucleic acid, typically at or near cleavage site(s). In an embodiment, the template nucleic acid is single stranded. In an alternate embodiment, the template nucleic acid is double stranded. In an embodiment, the template nucleic acid is DNA, e.g., double stranded DNA. In an alternate embodiment, the template nucleic acid is single stranded DNA. In an embodiment, the template nucleic acid is encoded on the same vector backbone, e.g. AAV genome, plasmid DNA, as the Cas9 and gRNA. In an embodiment, the template nucleic acid is excised from a vector backbone in vivo, e.g., it is flanked by gRNA recognition sequences. In an embodiment, the template nucleic acid comprises endogenous genomic sequence
• In an embodiment, the template nucleic acid alters the structure of the target position by participating in a homology directed repair event. In an embodiment, the template nucleic acid alters the sequence of the target position. In an embodiment, the template nucleic acid results in the incorporation of a modified, or non-naturally occurring base into the target nucleic acid.
• Typically, the template sequence undergoes a breakage mediated or catalyzed recombination with the target sequence. In an embodiment, the template nucleic acid includes sequence that corresponds to a site on the target sequence that is cleaved by an eaCas9 mediated cleavage event. In an embodiment, the template nucleic acid includes sequence that corresponds to both, a first site on the target sequence that is cleaved in a first Cas9 mediated event, and a second site on the target sequence that is cleaved in a second Cas9 mediated event.
• In an embodiment, the template nucleic acid can include sequence which results in an alteration in the coding sequence of a translated sequence, e.g., one which results in the substitution of one amino acid for another in a protein product, e.g., transforming a mutant allele into a wild type allele, transforming a wild type allele into a mutant allele, and/or introducing a stop codon, insertion of an amino acid residue, deletion of an amino acid residue, or a nonsense mutation.
• In other embodiments, the template nucleic acid can include sequence which results in an alteration in a non-coding sequence, e.g., an alteration in an exon or in a 5′ or 3′ non-translated or non-transcribed region. Such alterations include an alteration in a control element, e.g., a promoter, enhancer, and an alteration in a cis-acting or trans-acting control element.
• A template nucleic acid having homology with a target position in the HBB gene can be used to alter the structure of a target sequence. The template sequence can be used to alter an unwanted structure, e.g., an unwanted or mutant nucleotide.
• A template nucleic acid typically comprises the following components:
• [5′ homology arm]-[replacement sequence]-[3′ homology arm].
• The homology arms provide for recombination into the chromosome, thus replacing the undesired element, e.g., a mutation or signature, with the replacement sequence. In an embodiment, the homology arms flank the most distal cleavage sites.
• In an embodiment, the 3′ end of the 5′ homology arm is the position next to the 5′ end of the replacement sequence. In an embodiment, the 5′ homology arm can extend at least 10, 20, 30, 40, 50, 100, 200, 300, 400, 500, 600, 700, 800, 900, 1000, 1500, 2000, 3000, 4000, or 5000 nucleotides 5′ from the 5′ end of the replacement sequence.
• In an embodiment, the 5′ end of the 3′ homology arm is the position next to the 3′ end of the replacement sequence. In an embodiment, the 3′ homology arm can extend at least 10, 20, 30, 40, 50, 100, 200, 300, 400, 500, 600, 700, 800, 900, 1000, 1500, 2000, 3000, 4000, or 5000 nucleotides 3′ from the 3′ end of the replacement sequence.
• In an embodiment, to correct a mutation, the homology arms, e.g., the 5′ and 3′ homology arms, may each comprise about 1000 base pairs (bp) of sequence flanking the most distal gRNAs (e.g., 1000 bp of sequence on either side of the mutation).
• It is contemplated herein that one or both homology arms may be shortened to avoid including certain sequence repeat elements, e.g., Alu repeats or LINE elements. For example, a 5′ homology arm may be shortened to avoid a sequence repeat element. In other embodiments, a 3′ homology arm may be shortened to avoid a sequence repeat element. In some embodiments, both the 5′ and the 3′ homology arms may be shortened to avoid including certain sequence repeat elements.
• It is contemplated herein that template nucleic acids for correcting a mutation may be designed for use as a single-stranded oligonucleotide, e.g., a single-stranded oligodeoxynucleotide (ssODN). When using a ssODN, 5′ and 3′ homology arms may range up to about 200 base pairs (bp) in length, e.g., at least 25, 50, 75, 100, 125, 150, 175, or 200 bp in length. Longer homology arms are also contemplated for ssODNs as improvements in oligonucleotide synthesis continue to be made. In some embodiments, a longer homology arm is made by a method other than chemical synthesis, e.g., by denaturing a long double stranded nucleic acid and purifying one of the strands, e.g., by affinity for a strand-specific sequence anchored to a solid substrate.
• While not wishing to be bound by theory, in some embodiments alt-HDR proceeds more efficiently when the template nucleic acid has extended homology 5′ to the nick (i.e., in the 5′ direction of the nicked strand). Accordingly, in some embodiments, the template nucleic acid has a longer homology arm and a shorter homology arm, wherein the longer homology arm can anneal 5′ of the nick. In some embodiments, the arm that can anneal 5′ to the nick is at least 25, 50, 75, 100, 125, 150, 175, or 200, 300, 400, 500, 600, 700, 800, 900, 1000, 1500, 2000, 3000, 4000, or 5000 nucleotides from the nick or the 5′ or 3′ end of the replacement sequence. In some embodiments, the arm that can anneal 5′ to the nick is at least 10%, 20%, 30%, 40%, or 50% longer than the arm that can anneal 3′ to the nick. In some embodiments, the arm that can anneal 5′ to the nick is at least 2×, 3×, 4×, or 5× longer than the arm that can anneal 3′ to the nick. Depending on whether a ssDNA template can anneal to the intact strand or the nicked strand, the homology arm that anneals 5′ to the nick may be at the 5′ end of the ssDNA template or the 3′ end of the ssDNA template, respectively.
• Similarly, in some embodiments, the template nucleic acid has a 5′ homology arm, a replacement sequence, and a 3′ homology arm, such that the template nucleic acid has extended homology to the 5′ of the nick. For example, the 5′ homology arm and 3′ homology arm may be substantially the same length, but the replacement sequence may extend farther 5′ of the nick than 3′ of the nick. In some embodiments, the replacement sequence extends at least 10%, 20%, 30%, 40%, 50%, 2×, 3×, 4×, or 5× further to the 5′ end of the nick than the 3′ end of the nick. While not wishing to be bound by theory, in some embodiments alt-HDR proceeds more efficiently when the template nucleic acid is centered on the nick. Accordingly, in some embodiments, the template nucleic acid has two homology arms that are essentially the same size. For instance, the first homology arm of a template nucleic acid may have a length that is within 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, or 1% of the second homology arm of the template nucleic acid.
• Similarly, in some embodiments, the template nucleic acid has a 5′ homology arm, a replacement sequence, and a 3′ homology arm, such that the template nucleic acid extends substantially the same distance on either side of the nick. For example, the homology arms may have different lengths, but the replacement sequence may be selected to compensate for this. For example, the replacement sequence may extend further 5′ from the nick than it does 3′ of the nick, but the homology arm 5′ of the nick is shorter than the homology arm 3′ of the nick, to compensate. The converse is also possible, e.g., that the replacement sequence may extend further 3′ from the nick than it does 5′ of the nick, but the homology arm 3′ of the nick is shorter than the homology arm 5′ of the nick, to compensate.
• Exemplary Arrangements of Linear Nucleic Acid Template Systems
• In an embodiment, the nucleic acid template system is double stranded. In an embodiment, the nucleic acid template system is single stranded. In an embodiment, the nucleic acid template system comprises a single stranded portion and a double stranded portion. In an embodiment, the template nucleic acid comprises about 50 to 100, e.g., 55 to 95, 60 to 90, 65 to 85, or 70 to 80, base pairs, homology on either side of the nick and/or replacement sequence. In an embodiment, the template nucleic acid comprises about 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or 100 base pairs homology 5′ of the nick or replacement sequence, 3′ of the nick or replacement sequence, or both 5′ and 3′ of the nick or replacement sequences.
• In an embodiment, the template nucleic acid comprises about 150 to 200, e.g., 155 to 195, 160 to 190, 165 to 185, or 170 to 180, base pairs homology 3′ of the nick and/or replacement sequence. In an embodiment, the template nucleic acid comprises about 150, 155, 160, 165, 170, 175, 180, 185, 190, 195, or 200 base pairs homology 3′ of the nick or replacement sequence. In an embodiment, the template nucleic acid comprises less than about 100, 90, 80, 70, 60, 50, 40, 30, 20, 15, or 10 base pairs homology 5′ of the nick or replacement sequence.
• In an embodiment, the template nucleic acid comprises about 150 to 200, e.g., 155 to 195, 160 to 190, 165 to 185, or 170 to 180, base pairs homology 5′ of the nick and/or replacement sequence. In an embodiment, the template nucleic acid comprises about 150, 155, 160, 165, 170, 175, 180, 185, 190, 195, or 200 base pairs homology 5′ of the nick or replacement sequence. In an embodiment, the template nucleic acid comprises less than about 100, 90, 80, 70, 60, 50, 40, 30, 20, 15, or 10 base pairs homology 3′ of the nick or replacement sequence.
• Exemplary Template Nucleic Acids
• In an embodiment, the template nucleic acid is a single stranded nucleic acid. In another embodiment, the template nucleic acid is a double stranded nucleic acid. In some embodiments, the template nucleic acid comprises a nucleotide sequence, e.g., of one or more nucleotides, that will be added to or will template a change in the target nucleic acid. In other embodiments, the template nucleic acid comprises a nucleotide sequence that may be used to modify the target position. In other embodiments, the template nucleic acid comprises a nucleotide sequence, e.g., of one or more nucleotides, that corresponds to wild type sequence of the target nucleic acid, e.g., of the target position.
• The template nucleic acid may comprise a replacement sequence. In some embodiments, the template nucleic acid comprises a 5′ homology arm. In other embodiments, the template nucleic acid comprises a 3′ homology arm.
• In embodiments, the template nucleic acid is linear double stranded DNA. The length may be, e.g., about 150-200 base pairs, e.g., about 150, 160, 170, 180, 190, or 200 base pairs. The length may be, e.g., at least 150, 160, 170, 180, 190, or 200 base pairs. In some embodiments, the length is no greater than 150, 160, 170, 180, 190, or 200 base pairs. In some embodiments, a double stranded template nucleic acid has a length of about 160 base pairs, e.g., about 155-165, 150-170, 140-180, 130-190, 120-200, 110-210, 100-220, 90-230, or 80-240 base pairs.
• The template nucleic acid can be linear single stranded DNA. In embodiments, the template nucleic acid is (i) linear single stranded DNA that can anneal to the nicked strand of the target nucleic acid, (ii) linear single stranded DNA that can anneal to the intact strand of the target nucleic acid, (iii) linear single stranded DNA that can anneal to the transcribed strand of the target nucleic acid, (iv) linear single stranded DNA that can anneal to the non-transcribed strand of the target nucleic acid, or more than one of the preceding. The length may be, e.g., about 150-200 nucleotides, e.g., about 150, 160, 170, 180, 190, or 200 nucleotides. The length may be, e.g., at least 150, 160, 170, 180, 190, or 200 nucleotides. In some embodiments, the length is no greater than 150, 160, 170, 180, 190, or 200 nucleotides. In some embodiments, a single stranded template nucleic acid has a length of about 160 nucleotides, e.g., about 155-165, 150-170, 140-180, 130-190, 120-200, 110-210, 100-220, 90-230, or 80-240 nucleotides.
• In some embodiments, the template nucleic acid is circular double stranded DNA, e.g., a plasmid. In some embodiments, the template nucleic acid comprises about 500 to 1000 base pairs of homology on either side of the replacement sequence and/or the nick. In some embodiments, the template nucleic acid comprises about 300, 400, 500, 600, 700, 800, 900, 1000, 1500, or 2000 base pairs of homology 5′ of the nick or replacement sequence, 3′ of the nick or replacement sequence, or both 5′ and 3′ of the nick or replacement sequence. In some embodiments, the template nucleic acid comprises at least 300, 400, 500, 600, 700, 800, 900, 1000, 1500, or 2000 base pairs of homology 5′ of the nick or replacement sequence, 3′ of the nick or replacement sequence, or both 5′ and 3′ of the nick or replacement sequence. In some embodiments, the template nucleic acid comprises no more than 300, 400, 500, 600, 700, 800, 900, 1000, 1500, or 2000 base pairs of homology 5′ of the nick or replacement sequence, 3′ of the nick or replacement sequence, or both 5′ and 3′ of the nick or replacement sequence.
• In some embodiments, the template nucleic acid is an adenovirus vector, e.g., an AAV vector, e.g., a ssDNA molecule of a length and sequence that allows it to be packaged in an AAV capsid. The vector may be, e.g., less than 5 kb and may contain an ITR sequence that promotes packaging into the capsid. The vector may be integration-deficient. In some embodiments, the template nucleic acid comprises about 150 to 1000 nucleotides of homology on either side of the replacement sequence and/or the nick. In some embodiments, the template nucleic acid comprises about 100, 150, 200, 300, 400, 500, 600, 700, 800, 900, 1000, 1500, or 2000 nucleotides 5′ of the nick or replacement sequence, 3′ of the nick or replacement sequence, or both 5′ and 3′ of the nick or replacement sequence. In some embodiments, the template nucleic acid comprises at least 100, 150, 200, 300, 400, 500, 600, 700, 800, 900, 1000, 1500, or 2000 nucleotides 5′ of the nick or replacement sequence, 3′ of the nick or replacement sequence, or both 5′ and 3′ of the nick or replacement sequence. In some embodiments, the template nucleic acid comprises at most 100, 150, 200, 300, 400, 500, 600, 700, 800, 900, 1000, 1500, or 2000 nucleotides 5′ of the nick or replacement sequence, 3′ of the nick or replacement sequence, or both 5′ and 3′ of the nick or replacement sequence.
• In some embodiments, the template nucleic acid is a lentiviral vector, e.g., an IDLV (integration deficiency lentivirus). In some embodiments, the template nucleic acid comprises about 500 to 1000 base pairs of homology on either side of the replacement sequence and/or the nick. In some embodiments, the template nucleic acid comprises about 300, 400, 500, 600, 700, 800, 900, 1000, 1500, or 2000 base pairs of homology 5′ of the nick or replacement sequence, 3′ of the nick or replacement sequence, or both 5′ and 3′ of the nick or replacement sequence. In some embodiments, the template nucleic acid comprises at least 300, 400, 500, 600, 700, 800, 900, 1000, 1500, or 2000 base pairs of homology 5′ of the nick or replacement sequence, 3′ of the nick or replacement sequence, or both 5′ and 3′ of the nick or replacement sequence. In some embodiments, the template nucleic acid comprises no more than 300, 400, 500, 600, 700, 800, 900, 1000, 1500, or 2000 base pairs of homology 5′ of the nick or replacement sequence, 3′ of the nick or replacement sequence, or both 5′ and 3′ of the nick or replacement sequence.
• In many embodiments, the template nucleic acid comprises one or more mutations, e.g., silent mutations, that prevent Cas9 from recognizing and cleaving the template nucleic acid. The template nucleic acid may comprise, e.g., at least 1, 2, 3, 4, 5, 10, 20, or 30 silent mutations relative to the corresponding sequence in the genome of the cell to be altered. In embodiments, the template nucleic acid comprises at most 2, 3, 4, 5, 10, 20, 30, or 50 silent mutations relative to the corresponding sequence in the genome of the cell to be altered.
• In an embodiment, the template nucleic acid alters the structure of the target position by participating in a homology directed repair event. In an embodiment, the template nucleic acid alters the sequence of the target position. In an embodiment, the template nucleic acid results in the incorporation of a modified, or non-naturally occurring base into the target nucleic acid.
• Typically, the template sequence undergoes a breakage mediated or catalyzed recombination with the target sequence. In an embodiment, the template nucleic acid includes sequence that corresponds to a site on the target sequence that is cleaved by an eaCas9 mediated cleavage event. In an embodiment, the template nucleic acid includes sequence that corresponds to both, a first site on the target sequence that is cleaved in a first Cas9 mediated event, and a second site on the target sequence that is cleaved in a second Cas9 mediated event.
• In an embodiment, the template nucleic acid can include sequence which results in an alteration in the coding sequence of a translated sequence, e.g., one which results in the substitution of one amino acid for another in a protein product, e.g., transforming a mutant allele into a wild type allele, transforming a wild type allele into a mutant allele, and/or introducing a stop codon, insertion of an amino acid residue, deletion of an amino acid residue, or a nonsense mutation.
• In other embodiments, the template nucleic acid can include sequence which results in an alteration in a non-coding sequence, e.g., an alteration in an exon or in a 5′ or 3′ non-translated or non-transcribed region. Such alterations include an alteration in a control element, e.g., a promoter, enhancer, and an alteration in a cis-acting or trans-acting control element. A template nucleic acid having homology with a target position can be used to alter the structure of a target sequence. The template sequence can be used to alter an unwanted structure, e.g., an unwanted or mutant nucleotide.
• Exemplary template nucleic acids (also referred to herein as donor constructs) to correction a mutation, e.g., at E6, e.g., E6V, in the HBB gene, are provided.
• Suitable sequence for the 5′ homology arm can be selected from (e.g., includes a portion of) or include the following sequence:

• SEQ ID NO: 16257

  ATAGGAACTTGAATCAAGGAAATGATTTTAAAACGCAGTATTCTTAGTG

  GACTAGAGGAAAAAAATAATCTGAGCCAAGTAGAAGACCTTTTCCCCTC

  CTACCCCTACTTTCTAAGTCACAGAGGCTTTTTGTTCCCCCAGACACTC

  TTGCAGATTAGTCCAGGCAGAAACAGTTAGATGTCCCCAGTTAACCTCC

  TATTTGACACCACTGATTACCCCATTGATAGTCACACTTTGGGTTGTAA

  GTGACTTTTTATTTATTTGTATTTTTGACTGCATTAAGAGGTCTCTAGT

  TTTTTATCTCTTGTTTCCCAAAACCTAATAAGTAACTAATGCACAGAGC

  ACATTGATTTGTATTTATTCTATTTTTAGACATAATTTATTAGCATGCA

  TGAGCAAATTAAGAAAAACAACAACAAATGAATGCATATATATGTATAT

  GTATGTGTGTATATATACACACATATATATATATATTTTTTCTTTTCTT

  ACCAGAAGGTTTTAATCCAAATAAGGAGAAGATATGCTTAGAACCGAGG

  TAGAGTTTTCATCCATTCTGTCCTGTAAGTATTTTGCATATTCTGGAGA

  CGCAGGAAGAGATCCATCTACATATCCCAAAGCTGAATTATGGTAGACA

  AAACTCTTCCACTTTTAGTGCATCAACTTCTTATTTGTGTAATAAGAAA

  ATTGGGAAAACGATCTTCAATATGCTTACCAAGCTGTGATTCCAAATAT

  TACGTAAATACACTTGCAAAGGAGGATGTTTTTAGTAGCAATTTGTACT

  GATGGTATGGGGCCAAGAGATATATCTTAGAGGGAGGGCTGAGGGTTTG

  AAGTCCAACTCCTAAGCCAGTGCCAGAAGAGCCAAGGACAGGTACGGCT

  GTCATCACTTAGACCTCACCCTGTGGAGCCACACCCTAGGGTTGGCCAA

  TCTACTCCCAGGAGCAGGGAGGGCAGGAGCCAGGGCTGGGCATAAAAGT

  CAGGGCAGAGCCATCTATTGCTTACATTTGCTTCTGACACAACTGTGTT

  CACTAGCAACCTCAAACAGACACCATGGTGCATCTGACTCCTG

  (5′H arm)

• Suitable sequence for the 3′ homology arm can be selected from (e.g., includes a portion of) or include the following sequence:

• SEQ ID NO: 16258

  GGAGAAGTCTGCCGTTACTGCCCTGTGGGGCAAGGTGAACGTGGATGAA

  GTTGGTGGTGAGGCCCTGGGCAGGTTGGTATCAAGGTTACAAGACAGGT

  TTAAGGAGACCAATAGAAACTGGGCATGTGGAGACAGAGAAGACTCTTG

  GGTTTCTGATAGGCACTGACTCTCTCTGCCTATTGGTCTATTTTCCCAC

  CCTTAGGCTGCTGGTGGTCTACCCTTGGACCCAGAGGTTCTTTGAGTCC

  TTTGGGGATCTGTCCACTCCTGATGCTGTTATGGGCAACCCTAAGGTGA

  AGGCTCATGGCAAGAAAGTGCTCGGTGCCTTTAGTGATGGCCTGGCTCA

  CCTGGACAACCTCAAGGGCACCTTTGCCACACTGAGTGAGCTGCACTGT

  GACAAGCTGCACGTGGATCCTGAGAACTTCAGGGTGAGTCTATGGGACG

  CTTGATGTTTTCTTTCCCCTTCTTTTCTATGGTTAAGTTCATGTCATAG

  GAAGGGGATAAGTAACAGGGTACAGTTTAGAATGGGAAACAGACGAATG

  ATTGCATCAGTGTGGAAGTCTCAGGATCGTTTTAGTTTCTTTTATTTGC

  TGTTCATAACAATTGTTTTCTTTTGTTTAATTCTTGCTTTCTTTTTTTT

  TCTTCTCCGCAATTTTTACTATTATACTTAATGCCTTAACATTGTGTAT

  AACAAAAGGAAATATCTCTGAGATACATTAAGTAACTTAAAAAAAAACT

  TTACACAGTCTGCCTAGTACATTACTATTTGGAATATATGTGTGCTTAT

  TTGCATATTCATAATCTCCCTACTTTATTTTCTTTTATTTTTAATTGAT

  ACATAATCATTATACATATTTATGGGTTAAAGTGTAATGTTTTAATATG

  TGTACACATATTGACCAAATCAGGGTAATTTTGCATTTGTAATTTTAAA

  AAATGCTTTCTTCTTTTAATATACTTTTTTGTTTATCTTATTTCTAATA

  CTTTCCCTAATCTCTTTCTTTCAGGGCAATAATGATACAATGTATCATG

  CCTCTTTGCACCATTCTAAAGAATAACAGTGATAATTTCTGGGTTAAGG

  CAATAGCAATATCTCTGCATATAAATATTTCTGCATATAAATTGTAACT

  G (3′H arm)

• In an embodiment, the replacement sequence comprises or consists of an adenine (A) residue to correct the amino acid sequence to a glutamic acid (E) residue.
• In an embodiment, to correct a mutation, e.g., at E6, e.g., E6V, in the HBB gene, the homology arms, e.g., the 5′ and 3′ homology arms, may each comprise about 1000 base pairs (bp) of sequence flanking the most distal gRNAs (e.g., 1100 bp of sequence on either side of the mutation). The 5′ homology arm is shown as bold sequence, codon 6 is shown as underlined sequence, the inserted base to correct the mutation at E6, e.g., E6V, is shown as boxed sequence, and the 3′ homology arm is shown as no emphasis sequence.

• ATAGGAACTTGAATCAAGGAAATGATTTTAAAACGCAGTATTCTTAGTGGACTA
  GAGGAAAAAAATAATCTGAGCCAAGTAGAAGACCTTTTCCCCTCCTACCCCTAC
  TTTCTAAGTCACAGAGGCTTTTTGTTCCCCCAGACACTCTTGCAGATTAGTCCA
  GGCAGAAACAGTTAGATGTCCCCAGTTAACCTCCTATTTGACACCACTGATTAC
  CCCATTGATAGTCACACTTTGGGTTGTAAGTGACTTTTTATTTATTTGTATTTTT
  GACTGCATTAAGAGGTCTCTAGTTTTTTATCTCTTGTTTCCCAAAACCTAATAA
  GTAACTAATGCACAGAGCACATTGATTTGTATTTATTCTATTTTTAGACATAATT
  TATTAGCATGCATGAGCAAATTAAGAAAAACAACAACAAATGAATGCATATATA
  TGTATATGTATGTGTGTATATATACACACATATATATATATATTTTTTCTTTTCT
  TACCAGAAGGTTTTAATCCAAATAAGGAGAAGATATGCTTAGAACCGAGGTAG
  AGTTTTCATCCATTCTGTCCTGTAAGTATTTTGCATATTCTGGAGACGCAGGAA
  GAGATCCATCTACATATCCCAAAGCTGAATTATGGTAGACAAAACTCTTCCACT
  TTTAGTGCATCAACTTCTTATTTGTGTAATAAGAAAATTGGGAAAACGATCTTC
  AATATGCTTACCAAGCTGTGATTCCAAATATTACGTAAATACACTTGCAAAGGA
  GGATGTTTTTAGTAGCAATTTGTACTGATGGTATGGGGCCAAGAGATATATCTT
  AGAGGGAGGGCTGAGGGTTTGAAGTCCAACTCCTAAGCCAGTGCCAGAAGAGC
  CAAGGACAGGTACGGCTGTCATCACTTAGACCTCACCCTGTGGAGCCACACCC
  TAGGGTTGGCCAATCTACTCCCAGGAGCAGGGAGGGCAGGAGCCAGGGCTGG
  GCATAAAAGTCAGGGCAGAGCCATCTATTGCTTACATTTGCTTCTGACACAACT
  AGTCTGCCGTTACTGCCCTGTGGGGCAAGGTGAACGTGGATGAAGTTGGTGGTGAG
  GCCCTGGGCAGGTTGGTATCAAGGTTACAAGACAGGTTTAAGGAGACCAATAGAAA
  CTGGGCATGTGGAGACAGAGAAGACTCTTGGGTTTCTGATAGGCACTGACTCTCTCT
  GCCTATTGGTCTATTTTCCCACCCTTAGGCTGCTGGTGGTCTACCCTTGGACCCAGAG
  GTTCTTTGAGTCCTTTGGGGATCTGTCCACTCCTGATGCTGTTATGGGCAACCCTAAG
  GTGAAGGCTCATGGCAAGAAAGTGCTCGGTGCCTTTAGTGATGGCCTGGCTCACCTG
  GACAACCTCAAGGGCACCTTTGCCACACTGAGTGAGCTGCACTGTGACAAGCTGCA
  CGTGGATCCTGAGAACTTCAGGGTGAGTCTATGGGACGCTTGATGTTTTCTTTCCCCT
  TCTTTTCTATGGTTAAGTTCATGTCATAGGAAGGGGATAAGTAACAGGGTACAGTTT
  AGAATGGGAAACAGACGAATGATTGCATCAGTGTGGAAGTCTCAGGATCGTTTTAG
  TTTCTTTTATTTGCTGTTCATAACAATTGTTTTCTTTTGTTTAATTCTTGCTTTCTTTTT
  TTTTCTTCTCCGCAATTTTTACTATTATACTTAATGCCTTAACATTGTGTATAACAAA
  AGGAAATATCTCTGAGATACATTAAGTAACTTAAAAAAAAACTTTACACAGTCTGCC
  TAGTACATTACTATTTGGAATATATGTGTGCTTATTTGCATATTCATAATCTCCCTAC
  TTTATTTTCTTTTATTTTTAATTGATACATAATCATTATACATATTTATGGGTTAAAGT
  GTAATGTTTTAATATGTGTACACATATTGACCAAATCAGGGTAATTTTGCATTTGTAA
  TTTTAAAAAATGCTTTCTTCTTTTAATATACTTTTTTGTTTATCTTATTTCTAATACTTT
  CCCTAATCTCTTTCTTTCAGGGCAATAATGATACAATGTATCATGCCTCTTTGCACCA
  TTCTAAAGAATAACAGTGATAATTTCTGGGTTAAGGCAATAGCAATATCTCTGCATA
  TAAATATTTCTGCATATAAATTGTAACTG
  (Template Construct 1; SEQ ID NO: 16259)

• As described below in Table 27, shorter homology arms, e.g., 5′ and/or 3′ homology arms may be used.
• It is contemplated herein that one or both homology arms may be shortened to avoid including certain sequence repeat elements, e.g., Alu repeats, LINE elements. For example, a 5′ homology arm may be shortened to avoid a sequence repeat element. In another embodiment, a 3′ homology arm may be shortened to avoid a sequence repeat element. In an embodiment, both the 5′ and the 3′ homology arms may be shortened to avoid including certain sequence repeat elements.
• It is contemplated herein that template nucleic acids for correcting a mutation may designed for use as a single-stranded oligonucleotide (ssODN). When using a ssODN, 5′ and 3′ homology arms may range up to about 200 base pairs (bp) in length, e.g., at least 25, 50, 75, 100, 125, 150, 175, or 200 bp in length. Longer homology arms are also contemplated for ssODNs as improvements in oligonucleotide synthesis continue to be made.
• In an embodiment, an ssODN may be used to correct a mutation, e.g., E6V in the HBB gene. For example, the ssODN may include 50 bp 5′ and 3′ homology arms as shown below. The 5′ homology arm is shown as bold sequence, codon 6 is shown as underlined sequence, the inserted base to correct the E6V mutation is shown as boxed sequence, and the 3′ homology arm is shown as no emphasis sequence.

• ACTGTGTTCACTAGCAACCTCAAACAGACACCATGGTGCATCTGACTCCT
  GAAGT
  (Template Construct 2; SEQ ID NO: 16260)

• Silent Mutations in Donor Construct
• It is contemplated herein that Cas9 could potentially cleave donor constructs either prior to or following homology directed repair (e.g., homologous recombination), resulting in a possible non-homologous-end-joining event and further DNA sequence mutation at the chromosomal locus of interest. Therefore, to avoid cleavage of the donor sequence before and/or after Cas9-mediated homology directed repair, alternate versions of the donor sequence may be used where silent mutations are introduced. These silent mutations may disrupt Cas9 binding and cleavage, but not disrupt the amino acid sequence of the repaired gene. For example, mutations may include those made to a donor sequence to repair the HBB gene, the mutant form of which can cause Sickle Cell Disease. If gRNA HBB-6 with the 20-base target sequence CGUUACUGCCCUGUGGGGCA is used to insert a donor sequence including

• (SEQ ID NO: 16297)
  TGGATGAAGT,

  
  where the italic A is the base being corrected and the bracketed bases are those that match the guide RNA, the donor sequence may be changed to

• (SEQ ID NO: 16298)
  TGGATGAAGT,

  
  where the lowercase a has been changed from a G (lower case g in sequence ID xxx) at that position so that codon 15 still codes for the amino acid Arginine but the PAM sequence AGG has been modified to AGA to reduce or eliminate Cas9 cleavage at that locus.
• Table 27 below provides exemplary template nucleic acids. In an embodiment, the template nucleic acid includes the 5′ homology arm and the 3′ homology arm of a row from Table 27. In another embodiment, a 5′ homology arm from the first column can be combined with a 3′ homology arm from Table 27. In each embodiment, a combination of the 5′ and 3′ homology arms include a replacement sequence, e.g., an adenine (A) residue.

• TABLE 27
  5’ homology arm (the number of		3’ homology arm (the number of
  nucleotides from SEQ ID NO: 5’H,		nucleotides from SEQ ID NO: 3’H,
  beginning at the 3’ end of SEQ ID	Replacement	beginning at the 5’ end of SEQ ID
  NO: 5’H)	Sequence = A	NO: 3’H)
  10 or more		10 or more
  20 or more		20 or more
  50 or more		50 or more
  100 or more		100 or more
  150 or more		150 or more
  200 or more		200 or more
  250 or more		250 or more
  300 or more		300 or more
  350 or more		350 or more
  400 or more		400 or more
  450 or more		450 or more
  500 or more		500 or more
  550 or more		550 or more
  600 or more		600 or more
  650 or more		650 or more
  700 or more		700 or more
  750 or more		750 or more
  800 or more		800 or more
  850 or more		850 or more
  900 or more		900 or more
  1000 or more		1000 or more
  1100 or more		1100 or more
  1200 or more		1200 or more
  1300 or more		1300 or more
  1400 or more		1400 or more
  1500 or more		1500 or more
  1600 or more		1600 or more
  1700 or more		1700 or more
  1800 or more		1800 or more
  1900 or more		1900 or more
  1200 or more		1200 or more
  At least 50 but not long enough to		At least 50 but not long enough to
  include a repeated element.		include a repeated element.
  At least 100 but not long enough to		At least 100 but not long enough to
  include a repeated element.		include a repeated element.
  At least 150 but not long enough to		At least 150 but not long enough to
  include a repeated element.		include a repeated element.
  5 to 100 nucleotides		5 to 100 nucleotides
  10 to 150 nucleotides		10 to 150 nucleotides
  20 to 150 nucleotides		20 to 150 nucleotides
  Template Construct No. 1
  Template Construct No. 2

V.2 NHEJ Approaches for Gene Targeting
• As described herein, nuclease-induced non-homologous end-joining (NHEJ) can be used to target gene-specific knockouts. Nuclease-induced NHEJ can also be used to remove (e.g., delete) 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 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.3 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 D10A 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 enxymatically 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 1000 bp 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 DNAseI 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.4 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. 5 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 XRCC1, 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, XRCC1 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, XRCC1, 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, LIG1, PNK, PNKP, APE1, APTX, APLF, TDP1, LIG3, FEN1, CtIP, MRN, and ERCC1.
• 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.
• hMLH1 heterodimerizes with hPMS2 to form hMutL a 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 EXO1. (EXO1 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: EXO1, 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 R that adds a new complementary nucleotide into the repair gap and in the final step XRCC1/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 5′-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 6/c, 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, APE 1, 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 6, DNA Pol F or DNA Pol x, and DNA ligase I or XRCC1/Ligase III. Replicating cells tend to use DNA pol F and DNA ligase I, while non-replicating cells tend to use DNA Pol 6, DNA Pol K, and the XRCC1/Ligase III complex to perform the ligation step.
• NER can involve the following factors: XPA-G, POLH, XPF, ERCC1, XPA-G, and LIG1. Transcription-coupled NER (TC-NER) can involve the following factors: CSA, CSB, XPB, XPD, XPG, ERCC1, and TTDA. Additional factors that may promote the NER repair pathway include XPA-G, POLH, XPF, ERCC1, XPA-G, LIG1, CSA, CSB, XPA, XPB, XPC, XPD, XPF, XPG, TTDA, UVSSA, USP7, CETN2, RAD23B, UV-DDB, CAK subcomplex, RPA, and PCNA.
• Interstrand Crosslink (ICL)
• A dedicated pathway called the ICL repair pathway repairs interstrand crosslinks. Interstrand crosslinks, or covalent crosslinks between bases in different DNA strand, can occur during replication or transcription. ICL repair involves the coordination of multiple repair processes, in particular, nucleolytic activity, translesion synthesis (TLS), and HDR. Nucleases are recruited to excise the ICL on either side of the crosslinked bases, while TLS and HDR are coordinated to repair the cut strands. ICL repair can involve the following factors: endonucleases, e.g., XPF and RAD51C, endonucleases such as RAD51, translesion polymerases, e.g., DNA polymerase zeta and Rev1), 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 Rev1.
• Error-free postreplication repair (PRR) is another pathway for repairing a single stranded break left after a defective replication event.
V.6 Examples of gRNAs in Genome Editing Methods
• gRNA molecules as described herein can be used with Cas9 molecules that generate a double strand break or a single strand break to alter the sequence of a target nucleic acid, e.g., a target position or target genetic signature. gRNA molecules useful in these methods are described below.
• In an embodiment, the gRNA, e.g., a chimeric gRNA, is configured such that it comprises one or more of the following properties;
• a) it can position, e.g., when targeting a Cas9 molecule that makes double strand breaks, a double strand break (i) within 50, 100, 150, 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.
• 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), and c(i).
• In 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), and c(i).
• In an embodiment, the gRNA is configured such that in comprises properties: a(i), b(iii), and c(ii).
• In an embodiment, the gRNA is configured such that in comprises properties: a(i), b(iv), and c(i).
• In an embodiment, the gRNA is configured such that in comprises properties: a(i), b(iv), and c(ii).
• In an embodiment, the gRNA is configured such that in comprises properties: a(i), b(v), and c(i).
• In an embodiment, the gRNA is configured such that in comprises properties: a(i), b(v), and c(ii).
• In an embodiment, the gRNA is configured such that in comprises properties: a(i), b(vi), and c(i).
• In an embodiment, the gRNA is configured such that in comprises properties: a(i), b(vi), and c(ii).
• In an embodiment, the gRNA is configured such that in comprises properties: a(i), b(vii), and c(i).
• In an embodiment, the gRNA is configured such that in comprises properties: a(i), b(vii), and c(ii).
• In an embodiment, the gRNA is configured such that in comprises properties: a(i), b(viii), and c(i).
• In an embodiment, the gRNA is configured such that in comprises properties: a(i), b(viii), and c(ii).
• In an embodiment, the gRNA is configured such that in comprises properties: a(i), b(ix), and c(i).
• 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 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).
• In an embodiment, the gRNA, e.g., a chimeric gRNA, is configured such that it comprises one or more of the following properties;
• a) one or both of the gRNAs can position, e.g., when targeting a Cas9 molecule that makes single strand breaks, a single strand break within (i) 50, 100, 150, 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)
• • (i) the proximal and tail domain, when taken together, comprise at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides, e.g., at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides from a naturally occurring S. pyogenes, S. thermophilus, S. aureus, or N. meningitidis tail and proximal domain, or a sequence that differs by no more than 1, 2, 3, 4, 5; 6, 7, 8, 9 or 10 nucleotides therefrom;
  • (ii) there are at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides 3′ to the last nucleotide of the second complementarity domain, e.g., at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides from the corresponding sequence of a naturally occurring S. pyogenes, S. thermophilus, S. aureus, or N. meningitidis gRNA, or a sequence that differs by no more than 1, 2, 3, 4, 5; 6, 7, 8, 9 or 10 nucleotides therefrom;
  • (iii) there are at least 16, 19, 21, 26, 31, 32, 36, 41, 46, 50, 51, or 54 nucleotides 3′ to the last nucleotide of the second complementarity domain that is complementary to its corresponding nucleotide of the first complementarity domain, e.g., at least 16, 19, 21, 26, 31, 32, 36, 41, 46, 50, 51, or 54 nucleotides from the corresponding sequence of a naturally occurring S. pyogenes, S. thermophilus, S. aureus, or N. meningitidis gRNA, or a sequence that differs by no more than 1, 2, 3, 4, 5; 6, 7, 8, 9 or 10 nucleotides therefrom;
  • (iv) the tail domain is at least 10, 15, 20, 25, 30, 35 or 40 nucleotides in length, e.g., it comprises at least 10, 15, 20, 25, 30, 35 or 40 nucleotides from a naturally occurring S. pyogenes, S. thermophilus, S. aureus, or N. meningitidis tail domain, or a sequence that differs by no more than 1, 2, 3, 4, 5; 6, 7, 8, 9 or 10 nucleotides therefrom; or
  • (v) the tail domain comprises 15, 20, 25, 30, 35, 40 nucleotides or all of the corresponding portions of a naturally occurring tail domain, e.g., a naturally occurring S. pyogenes, S. thermophilus, S. aureus, or N. meningitidis tail domain.
• In an embodiment, the gRNA is configured such that it comprises properties: a and b(i).
• In an embodiment, the gRNA is configured such that it comprises properties: a and b(ii).
• In an embodiment, the gRNA is configured such that it comprises properties: a and b(iii).
• In an embodiment, the gRNA is configured such that it comprises properties: a and 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), and c(i).
• In 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), and c(i).
• In an embodiment, the gRNA is configured such that in comprises properties: a(i), b(iii), and c(ii).
• In an embodiment, the gRNA is configured such that in comprises properties: a(i), b(iv), and c(i).
• In an embodiment, the gRNA is configured such that in comprises properties: a(i), b(iv), and c(ii).
• In an embodiment, the gRNA is configured such that in comprises properties: a(i), b(v), and c(i).
• In an embodiment, the gRNA is configured such that in comprises properties: a(i), b(v), and c(ii).
• In an embodiment, the gRNA is configured such that in comprises properties: a(i), b(vi), and c(i).
• In an embodiment, the gRNA is configured such that in comprises properties: a(i), b(vi), and c(ii).
• In an embodiment, the gRNA is configured such that in comprises properties: a(i), b(vii), and c(i).
• In an embodiment, the gRNA is configured such that in comprises properties: a(i), b(vii), and c(ii).
• In an embodiment, the gRNA is configured such that in comprises properties: a(i), b(viii), and c(i).
• In an embodiment, the gRNA is configured such that in comprises properties: a(i), b(viii), and c(ii).
• In an embodiment, the gRNA is configured such that in comprises properties: a(i), b(ix), and c(i).
• 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 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).
• 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 840, e.g., the H840A.
• In an embodiment, the gRNAs are used with a Cas9 nickase molecule having RuvC activity, e.g., a Cas9 molecule having the HNH activity inactivated, e.g., a Cas9 molecule having a mutation at N863, e.g., the N863A mutation.
• In an embodiment, a pair of gRNAs, e.g., a pair of chimeric gRNAs, comprising a first and a second gRNA, is configured such that they comprises one or more of the following properties;
• a) one or both of the gRNAs can position, e.g., when targeting a Cas9 molecule that makes single strand breaks, a single strand break within (i) 50, 100, 150, 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;
• c) for one or both:
• • (i) the proximal and tail domain, when taken together, comprise at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides, e.g., at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides from a naturally occurring S. pyogenes, S. thermophilus, S. aureus, or N. meningitidis tail and proximal domain, or a sequence that differs by no more than 1, 2, 3, 4, 5; 6, 7, 8, 9 or 10 nucleotides therefrom;
  • (ii) there are at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides 3′ to the last nucleotide of the second complementarity domain, e.g., at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides from the corresponding sequence of a naturally occurring S. pyogenes, S. thermophilus, S. aureus, or N. meningitidis gRNA, or a sequence that differs by no more than 1, 2, 3, 4, 5; 6, 7, 8, 9 or 10 nucleotides therefrom;
  • (iii) there are at least 16, 19, 21, 26, 31, 32, 36, 41, 46, 50, 51, or 54 nucleotides 3′ to the last nucleotide of the second complementarity domain that is complementary to its corresponding nucleotide of the first complementarity domain, e.g., at least 16, 19, 21, 26, 31, 32, 36, 41, 46, 50, 51, or 54 nucleotides from the corresponding sequence of a naturally occurring S. pyogenes, S. thermophilus, S. aureus, or N. meningitidis gRNA, or a sequence that differs by no more than 1, 2, 3, 4, 5; 6, 7, 8, 9 or 10 nucleotides therefrom;
  • (iv) the tail domain is at least 10, 15, 20, 25, 30, 35 or 40 nucleotides in length, e.g., it comprises at least 10, 15, 20, 25, 30, 35 or 40 nucleotides from a naturally occurring S. pyogenes, S. thermophilus, S. aureus, or N. meningitidis tail domain; or, or a sequence that differs by no more than 1, 2, 3, 4, 5; 6, 7, 8, 9 or 10 nucleotides therefrom; or
  • (v) the tail domain comprises 15, 20, 25, 30, 35, 40 nucleotides or all of the corresponding portions of a naturally occurring tail domain, e.g., a naturally occurring S. pyogenes, S. thermophilus, S. aureus, or N. meningitidis tail domain;
• d) the gRNAs are configured such that, when hybridized to target nucleic acid, they are separated by 0-50, 0-100, 0-200, at least 10, at least 20, at least 30 or at least 50 nucleotides;
• e) the breaks made by the first gRNA and second gRNA are on different strands; and
• f) the PAMs are facing outwards.
• In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a and b(i).
• In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a and b(ii).
• In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a and b(iii).
• In an embodiment, one or both of the gRNAs 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., inducing a mutation in) the HBB and/or BCL11A target genes, e.g., as described herein. In an embodiment, the expression of the HBB and/or BCL11A target genes is modulated, e.g., in vivo. In another embodiment, the expression of the HBB and/or BCL11A target genes 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., inducing a mutation in) the HBB and/or BCL11A target genes and/or modulating the expression of the HBB and/or BCL11A target genes, 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 (e.g., a Cas9 molecule/gRNA molecule complex), and a donor template nucleic acid, can be delivered or formulated in a variety of forms, see, e.g., Tables 34-35. 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-1a, 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 H1, 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 34 provides examples of how the components can be formulated, delivered, or administered.

• TABLE 34
  Elements

  		Donor
  Cas9	gRNA	Template
  Molecule(s)	Molecule(s)	Nucleic Acid	Comments

  DNA	DNA	DNA	In this embodiment, a Cas9 molecule, typically
  			an eaCas9 molecule, and a gRNA are transcribed
  			from DNA. In this embodiment, they are
  			encoded on separate molecules. In this
  			embodiment, the donor template is provided as a
  			separate DNA molecule.

  DNA	DNA	In this embodiment, a Cas9 molecule, typically
  		an eaCas9 molecule, and a gRNA are transcribed
  		from DNA. In this embodiment, they are
  		encoded on separate molecules. In this
  		embodiment, the donor template is provided on
  		the same DNA molecule that encodes the gRNA.

  DNA	DNA	In this embodiment, a Cas9 molecule, typically
  		an eaCas9 molecule, and a gRNA are transcribed
  		from DNA, here from a single molecule. In this
  		embodiment, the donor template is provided as a
  		separate DNA molecule.

  DNA	DNA	DNA	In this embodiment, a Cas9 molecule, typically
  			an eaCas9 molecule, and a gRNA are transcribed
  			from DNA. In this embodiment, they are
  			encoded on separate molecules. In this
  			embodiment, the donor template is provided on
  			the same DNA molecule that encodes the Cas9.
  DNA	RNA	DNA	In this embodiment, a Cas9 molecule, typically
  			an eaCas9 molecule, is transcribed from DNA,
  			and a gRNA is provided as in vitro transcribed or
  			synthesized RNA. In this embodiment, the donor
  			template is provided as a separate DNA molecule.
  DNA	RNA	DNA	In this embodiment, a Cas9 molecule, typically
  			an eaCas9 molecule, is transcribed from DNA,
  			and a gRNA is provided as in vitro transcribed or

  	synthesized RNA. In this embodiment, the donor
  	template is provided on the same DNA molecule
  	that encodes the Cas9.

  mRNA	RNA	DNA	In this embodiment, a Cas9 molecule, typically
  			an eaCas9 molecule, is translated from in vitro
  			transcribed mRNA, and a gRNA is provided as in
  			vitro transcribed or synthesized RNA. In this
  			embodiment, the donor template is provided as a
  			DNA molecule.
  mRNA	DNA	DNA	In this embodiment, a Cas9 molecule, typically
  			an eaCas9 molecule, is translated from in vitro
  			transcribed mRNA, and a gRNA is transcribed
  			from DNA. In this embodiment, the donor
  			template is provided as a separate DNA molecule.

  mRNA	DNA	In this embodiment, a Cas9 molecule, typically
  		an eaCas9 molecule, is translated from in vitro
  		transcribed mRNA, and a gRNA is transcribed
  		from DNA. In this embodiment, the donor
  		template is provided on the same DNA molecule
  		that encodes the gRNA.

  Protein	DNA	DNA	In this embodiment, a Cas9 molecule, typically
  			an eaCas9 molecule, is provided as a protein, and
  			a gRNA is transcribed from DNA. In this
  			embodiment, the donor template is provided as a
  			separate DNA molecule.

  Protein	DNA	In this embodiment, a Cas9 molecule, typically
  		an eaCas9 molecule, is provided as a protein, and
  		a gRNA is transcribed from DNA. In this
  		embodiment, the donor template is provided on
  		the same DNA molecule that encodes the gRNA.

  Protein	RNA	DNA	In this embodiment, an eaCas9 molecule is
  			provided as a protein, and a gRNA is provided as
  			transcribed or synthesized RNA. In this
  			embodiment, the donor template is provided as a
  			DNA molecule.

• Table 35 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 35
  	Delivery	Duration
  	into Non-	of	Genome	Type of
  	Dividing	Expres-	Inte-	Molecule
  Delivery Vector/Mode	Cells	sion	gration	Delivered
  Physical (eg,	YES	Transient	NO	Nucleic
  electroporation,				Acids
  particle gun, Calcium				and
  Phosphate transfection)				Proteins

  Viral	Retrovirus	NO	Stable	YES	RNA
  	Lentivirus	YES	Stable	YES/NO	RNA
  				with
  				modi-
  				fications
  	Adenovirus	YES	Transient	NO	DNA
  	Adeno-	YES	Stable	NO	DNA
  	Associated
  	Virus (AAV)
  	Vaccinia	YES	Very	NO	DNA
  	Virus		Transient
  	Herpes	YES	Stable	NO	DNA
  	Simplex
  	Virus
  Non-	Cationic	YES	Transient	Depends	Nucleic
  Viral	Liposomes			on	Acids
  				what is	and
  				delivered	Proteins
  	Polymeric	YES	Transient	Depends	Nucleic
  	Nano-			on	Acids
  	particles			what is	and
  				delivered	Proteins
  Bio-	Attenuated	YES	Transient	NO	Nucleic
  logical	Bacteria				Acids
  Non-	Engineered	YES	Transient	NO	Nucleic
  Viral	Bacteriophages				Acids
  Delivery	Mammalian	YES	Transient	NO	Nucleic
  Vehicles	Virus-like				Acids
  	Particles
  	Biological	YES	Transient	NO	Nucleic
  	liposomes:				Acids
  	Erythrocyte
  	Ghosts and
  	Exosomes

  
  DNA-Based Delivery of a Cas9 Molecule and/or One or More gRNA Molecule and/or a Donor Template
• Nucleic acids (e.g., DNA) encoding a Cas9 molecule (e.g., an eaCas9 molecule), a gRNA molecule, a donor template nucleic acid, or any combination (e.g., two or all) thereof, can be administered to subjects or delivered into cells by art-known methods or as described herein. For example, Cas9-encoding and/or gRNA-encoding DNA, as well as donor template nucleic acids, can be delivered, e.g., by vectors (e.g., viral or non-viral vectors), non-vector based methods (e.g., using naked DNA or DNA complexes), or a combination thereof. Donor template molecules can be administered to subjects or delivered into cells by art-known methods or as described herein. For example, donor template molecules 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.
• Nucleic acids (e.g., DNA) encoding Cas9 molecules (e.g., eaCas9 molecules) and/or gRNA molecules can be conjugated to molecules to promote uptake by the target cells (e.g., the target cells describe herein). Donor template molecules can be conjugated to molecules to promote uptake by the target cells (e.g., the target cells describe 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 nucleic acid sequence is delivered by a recombinant retrovirus. In an embodiment, the donor template nucleic acid 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 nucleic acid sequence is delivered by a recombinant lentivirus. In an embodiment, the donor template nucleic acid is delivered by a recombinant lentivirus. For example, the lentivirus is replication-defective, e.g., does not comprise one or more genes required for viral replication.
• In an embodiment, the Cas9- and/or gRNA-encoding DNA is delivered by a recombinant adenovirus. In an embodiment, the donor template nucleic acid 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 an embodiment, the donor template nucleic acid is delivered by a recombinant AAV. In some embodiments, the AAV does not incorporate its genome into that of a host cell, e.g., a target cell as describe herein. In an embodiment, the AAV can incorporate 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 l0, 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.rh10, AAV.rh32/33, AAV.rh43, AAV.rh64R1, 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.rh10, AAV.rh32/33, AAV.rh43, or AAV.rh64R1.
• In an embodiment, the Cas9- and/or gRNA-encoding DNA is delivered by a chimeric AAV capsid. In an embodiment, the donor template nucleic acid is delivered by a chimeric AAV capsid. Exemplary chimeric AAV capsids include, but are not limited to, AAV9i1, 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 E1A and/or E1B genes from adenovirus. The cell line is also infected with adenovirus as a helper. The helper virus (e.g., adenovirus or HSV) or helper plasmid promotes replication of the AAV vector and expression of AAV genes from the helper plasmid with ITRs. The helper plasmid is not packaged in significant amounts due to a lack of ITR sequences. Contamination with adenovirus can be reduced by, e.g., heat treatment to which adenovirus is more sensitive than AAV.
• In an embodiment, the viral vector has the ability of cell type and/or tissue type recognition. For example, the viral vector can be pseudotyped with a different/alternative viral envelope glycoprotein; engineered with a cell type-specific receptor (e.g., geneticmodification of the viral envelope glycoproteins to incorporate targeting ligands such as a peptide ligand, a single chain antibodie, a growth factor); and/or engineered to have a molecular bridge with dual specificities with one end recognizing a viral glycoprotein and the other end recognizing a moiety of the target cell surface (e.g., ligand-receptor, monoclonal antibody, avidin-biotin and chemical conjugation).
• In an embodiment, the viral vector achieves cell type specific expression. For example, a tissue-specific promoter can be constructed to restrict expression of the transgene (Cas 9 and gRNA) in only the target cell. The specificity of the vector can also be mediated by microRNA-dependent control of transgene expression. In an embodiment, the viral vector has increased efficiency of fusion of the viral vector and a target cell membrane. For example, a fusion protein such as fusion-competent hemagglutin (HA) can be incorporated to increase viral uptake into cells. In an embodiment, the viral vector has the ability of nuclear localization. For example, aviruse that requires the breakdown of the nuclear envelope (during cell division) and therefore will not infect a non-diving cell can be altered to incorporate a nuclear localization peptide in the matrix protein of the virus thereby enabling the transduction of non-proliferating cells.
• In some embodiments, the Cas9- and/or gRNA-encoding DNA is delivered by a non-vector based method (e.g., using naked DNA or DNA complexes). For example, the DNA can be delivered, e.g., by organically modified silica or silicate (Ormosil), electroporation, transient cell compression or squeezing (e.g., as described in Lee, et al., Nano Lett 12: 6322-27), gene gun, sonoporation, magnetofection, lipid-mediated transfection, dendrimers, inorganic nanoparticles, calcium phosphates, or a combination thereof.
• In an embodiment, delivery via electroporation comprises mixing the cells with the Cas9- and/or gRNA-encoding DNA in a cartridge, chamber or cuvette and applying one or more electrical impulses of defined duration and amplitude. In an embodiment, delivery via electroporation is performed using a system in which cells are mixed with the Cas9- and/or gRNA-encoding DNA in a vessel connected to a device (eg, a pump) which feeds the mixture into a cartridge, chamber or cuvette wherein one or more electrical impulses of defined duration and amplitude are applied, after which the cells are delivered to a second vessel.
• In an embodiment, the Cas9- and/or gRNA-encoding DNA is delivered by a combination of a vector and a non-vector based method. In an embodiment, the donor template nucleic acid is delivered by a combination of a vector and a non-vector based method. For example, a virosome comprises a liposome combined with an inactivated virus (e.g., HIV or influenza virus), which can result in more efficient gene transfer, e.g., in a respiratory epithelial cell than either a viral or a liposomal method alone.
• In an embodiment, the delivery vehicle is a non-viral vector. In an embodiment, the non-viral vector is an inorganic nanoparticle. Exemplary inorganic nanoparticles include, e.g., magnetic nanoparticles (e.g., Fe₃MnO₂) or silica. The outer surface of the nanoparticle can be conjugated with a positively charged polymer (e.g., polyethylenimine, polylysine, polyserine) which allows for attachment (e.g., conjugation or entrapment) of payload. In an embodiment, the non-viral vector is an organic nanoparticle (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 36.

• TABLE 36
  Lipids Used for Gene Transfer

  Lipid	Abbreviation	Feature
  1,2-Dioleoyl-sn-glycero-3-phosphatidylcholine	DOPC	Helper
  1,2-Dioleoyl-sn-glycero-3- phosphatidylethanolamine	DOPE	Helper
  Cholesterol		Helper
  N-[1-(2,3-Dioleyloxy)prophyl]N,N,N- trimethylammonium	DOTMA	Cationic
  chloride
  l,2-Dioleoyloxy-3-trimethylammonium-propane	DOTAP	Cationic
  Dioctadecylamidoglycylspermine	DOGS	Cationic
  N-(3-Aminopropyl)-N,N-dimethyl- 2,3-bis(dodecyloxy)-1-	GAP-DLRIE	Cationic
  propanaminium bromide
  Cetyltrimethylammonium bromide	CTAB	Cationic
  6-Lauroxyhexyl ornithinate	LHON	Cationic
  1-(2,3-Dioleoyloxypropyl)-2,4,6- trimethylpyridinium	2Oc	Cationic
  2,3-Dioleyloxy-N-[2(sperminecarboxamido- ethyl]-N,N-dimethyl-	DOSPA	Cationic
  1-propanaminium trifluoroacetate
  1,2-Dioleyl-3-trimethylammonium-propane	DOPA	Cationic
  N-(2-Hydroxyethyl)-N,N-dimethyl- 2,3-bis(tetradecyloxy)-1-	MDRIE	Cationic
  propanaminium bromide
  Dimyristooxypropyl dimethyl hydroxyethyl ammonium bromide	DMRI	Cationic
  3β-[N-(N’,N’-Dimethylaminoethane)- carbamoyl]cholesterol	DC-Chol	Cationic
  Bis-guanidium-tren-cholesterol	BGTC	Cationic
  1,3-Diodeoxy-2-(6-carboxy- spermyl)-propylamide	DOSPER	Cationic
  Dimethyloctadecylammonium bromide	DDAB	Cationic
  Dioctadecylamidoglicylspermidin	DSL	Cationic
  rac-[(2,3-Dioctadecyloxypropyl)(2- hydroxyethyl)]-	CLIP-1	Cationic
  dimethylammonium chloride
  rac-[2(2,3-Dihexadecyloxypropyl-	CLIP-6	Cationic
  oxymethyloxy)ethyl]trimethylammonium bromide
  Ethyldimyristoylphosphatidylcholine	EDMPC	Cationic
  1,2-Distearyloxy-N,N-dimethyl- 3-aminopropane	DSDMA	Cationic
  1,2-Dimyristoyl-trimethylammonium propane	DMTAP	Cationic
  O,O’-Dimyristyl-N-lysyl aspartate	DMKE	Cationic
  1,2-Distearoyl-sn-glycero-3- ethylphosphocholine	DSEPC	Cationic
  N-Palmitoyl D-erythro-sphingosyl carbamoyl-spermine	CCS	Cationic
  N-t-Butyl-N0-tetradecyl-3- tetradecylaminopropionamidine	diC14-amidine	Cationic
  Octadecenolyoxy[ethyl-2- heptadecenyl-3 hydroxyethyl]	DOTIM	Cationic
  imidazolinium chloride
  N1-Cholesteryloxycarbonyl-3,7- diazanonane-1,9-diamine	CDAN	Cationic
  2-(3-[Bis(3-amino-propyl)- amino]propylamino)-N-	RPR209120	Cationic
  ditetradecylcarbamoylme-ethyl-acetamide

• Exemplary polymers for gene transfer are shown below in Table 37.

• TABLE 37
  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(β-aminoester)
  	Poly(4-hydroxy-L-proline ester)	PHP
  	Poly(allylamine)
  	Poly (α-[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 (eg, 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) promoting uptake by the target cells (e.g., target cells described herein).
• In an embodiment, delivery via electroporation comprises mixing the cells with the RNA encoding Cas9 molecules (e.g., eaCas9 molecules, eiCas9 molecules or eiCas9 fusion proteins) and/or gRNA molecules, with or without donor template nucleic acid molecules, in a cartridge, chamber or cuvette and applying one or more electrical impulses of defined duration and amplitude. In an embodiment, delivery via electroporation is performed using a system in which cells are mixed with the RNA encoding Cas9 molecules (e.g., eaCas9 molecules, eiCas9 molecules or eiCas9 fusion proteins) and/or gRNA molecules, with or without donor template nucleic acid molecules in a vessel connected to a device (eg, a pump) which feeds the mixture into a cartridge, chamber or cuvette wherein one or more electrical impulses of defined duration and amplitude are applied, after which the cells are delivered to a second vessel. 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).
• 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 (eg, 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 proteins) and/or gRNA molecules, with or without donor nucleic acid, in a cartridge, chamber or cuvette and applying one or more electrical impulses of defined duration and amplitude. In an embodiment, delivery via electroporation is performed using a system in which cells are mixed with the Cas9 molecules (e.g., eaCas9 molecules, eiCas9 molecules or eiCas9 fusion proteins) and/or gRNA molecules, with or without donor nucleic acid in a vessel connected to a device (eg, a pump) which feeds the mixture into a cartridge, chamber or cuvette wherein one or more electrical impulses of defined duration and amplitude are applied, after which the cells are delivered to a second vessel. 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).
• 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, gRNA molecule, or template nucleic acid. For example, the modes of delivery can result in different tissue distribution, different half-life, or different temporal distribution, e.g., in a selected compartment, tissue, or organ.
• Some modes of delivery, e.g., delivery by a nucleic acid vector that persists in a cell, or in progeny of a cell, e.g., by autonomous replication or insertion into cellular nucleic acid, result in more persistent expression of and presence of a component. Examples include viral, e.g., adeno-associated virus or lentivirus, delivery.
• By way of example, the components, e.g., a Cas9 molecule and a gRNA molecule, can be delivered by modes that differ in terms of resulting half-life or persistent of the delivered component the body, or in a particular compartment, tissue or organ. In an embodiment, a gRNA molecule can be delivered by such modes. The Cas9 molecule component can be delivered by a mode which results in less persistence or less exposure to the body or a particular compartment or tissue or organ.
• More generally, in an embodiment, a first mode of delivery is used to deliver a first component and a second mode of delivery is used to deliver a second component. The first mode of delivery confers a first pharmacodynamic or pharmacokinetic property. The first pharmacodynamic property can be, e.g., distribution, persistence, or exposure, of the component, or of a nucleic acid that encodes the component, in the body, a compartment, tissue or organ. The second mode of delivery confers a second pharmacodynamic or pharmacokinetic property. The second pharmacodynamic property can be, e.g., distribution, persistence, or exposure, of the component, or of a nucleic acid that encodes the component, in the body, a compartment, tissue or organ.
• In an embodiment, the first pharmacodynamic or pharmacokinetic property, e.g., distribution, persistence or exposure, is more limited than the second pharmacodynamic or pharmacokinetic property.
• In an embodiment, the first mode of delivery is selected to optimize, e.g., minimize, a pharmacodynamic or pharmacokinetic property, e.g., distribution, persistence or exposure.
• In an embodiment, the second mode of delivery is selected to optimize, e.g., maximize, a pharmacodynamic or pharmcokinetic property, e.g., distribution, persistence or exposure.
• In an embodiment, the first mode of delivery comprises the use of a relatively persistent element, e.g., a nucleic acid, e.g., a plasmid or viral vector, e.g., an AAV or lentivirus. As such vectors are relatively persistent product transcribed from them would be relatively persistent.
• In an embodiment, the second mode of delivery comprises a relatively transient element, e.g., an RNA or protein.
• In an embodiment, the first component comprises gRNA, and the delivery mode is relatively persistent, e.g., the gRNA is transcribed from a plasmid or viral vector, e.g., an AAV or lentivirus. Transcription of these genes would be of little physiological consequence because the genes do not encode for a protein product, and the gRNAs are incapable of acting in isolation. The second component, a Cas9 molecule, is delivered in a transient manner, for example as mRNA or as protein, ensuring that the full Cas9 molecule/gRNA molecule complex is only present and active for a short period of time.
• Furthermore, the components can be delivered in different molecular form or with different delivery vectors that complement one another to enhance safety and tissue specificity.
• Use of differential delivery modes can enhance performance, safety and efficacy. E.g., the likelihood of an eventual off-target modification can be reduced. Delivery of immunogenic components, e.g., Cas9 molecules, by less persistent modes can reduce immunogenicity, as peptides from the bacterially-derived Cas enzyme are displayed on the surface of the cell by MHC molecules. A two-part delivery system can alleviate these drawbacks.
• Differential delivery modes can be used to deliver components to different, but overlapping target regions. The formation active complex is minimized outside the overlap of the target regions. Thus, in an embodiment, a first component, e.g., a gRNA molecule is delivered by a first delivery mode that results in a first spatial, e.g., tissue, distribution. A second component, e.g., a Cas9 molecule is delivered by a second delivery mode that results in a second spatial, e.g., tissue, distribution. In an embodiment, the first mode comprises a first element selected from a liposome, nanoparticle, e.g., polymeric nanoparticle, and a nucleic acid, e.g., viral vector. The second mode comprises a second element selected from the group. In an embodiment, the first mode of delivery comprises a first targeting element, e.g., a cell specific receptor or an antibody, and the second mode of delivery does not include that element. In embodiment, the second mode of delivery comprises a second targeting element, e.g., a second cell specific receptor or second antibody.
• When the Cas9 molecule is delivered in a virus delivery vector, a liposome, or polymeric nanoparticle, there is the potential for delivery to and therapeutic activity in multiple tissues, when it may be desirable to only target a single tissue. A two-part delivery system can resolve this challenge and enhance tissue specificity. If the gRNA molecule and the Cas9 molecule are packaged in separated delivery vehicles with distinct but overlapping tissue tropism, the fully functional complex is only be formed in the tissue that is targeted by both vectors.
Ex Vivo Delivery
• In an embodiment, components described in Table 34 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 35.
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), O(CH₂CH₂O)_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 C_1-6 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, O(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(O)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 1′ position on the sugar, e.g., alpha-nucleosides. The modified nucleic acids can also include “abasic” sugars, which lack a nucleobase at C-1′. 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 α-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 (m³U), 5-methoxy-uridine (mo⁵U), uridine 5-oxyacetic acid (cmo⁵U), uridine 5-oxyacetic acid methyl ester (memo⁵U), 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-uridine (mnm⁵se²U), 5-carbamoylmethyl-uridine (ncm⁵U), 5-carboxymethylaminomethyl-uridine (cmnm⁵U), 5-carboxymethylaminomethyl-2-thio-uridine (cmnm⁵s2U), 5-propynyl-uridine, 1-propynyl-pseudouridine, 5-taurinomethyl-uridine (τCm⁵U), 1-taurinomethyl-pseudouridine, 5-taurinomethyl-2-thio-uridine(τm⁵s2U), 1-taurinomethyl-4-thio-pseudouridine, 5-methyl-uridine (m⁵U, i.e., having the nucleobase deoxythymine), 1-methyl-pseudouridine (m¹ψ), 5-methyl-2-thio-uridine (m⁵s2U), 1-methyl-4-thio-pseudouridine (m¹s⁴ψ), 4-thio-1-methyl-pseudouridine, 3-methyl-pseudouridine (m³ψ), 2-thio-1-methyl-pseudouridine, 1-methyl-1-deaza-pseudouridine, 2-thio-1-methyl-1-deaza-pseudouridine, dihydrouridine (D), dihydropseudouridine, 5,6-dihydrouridine, 5-methyl-dihydrouridine (m⁵D), 2-thio-dihydrouridine, 2-thio-dihydropseudouridine, 2-methoxy-uridine, 2-methoxy-4-thio-uridine, 4-methoxy-pseudouridine, 4-methoxy-2-thio-pseudouridine, N1-methyl-pseudouridine, 3-(3-amino-3-carboxypropyl)uridine (acp³U), 1-methyl-3-(3-amino-3-carboxypropyl)pseudouridine (acp³ψ), 5-(isopentenylaminomethyl)uridine (inm⁵U), 5-(isopentenylaminomethyl)-2-thio-uridine (inm⁵s2U), α-thio-uridine, 2′-O-methyl-uridine (Um), 5,2′-O-dimethyl-uridine (m⁵Um), 2′-O-methyl-pseudouridine (Wm), 2-thio-2′-O-methyl-uridine (s2Um), 5-methoxycarbonylmethyl-2′-O-methyl-uridine (mcm⁵Um), 5-carbamoylmethyl-2′-O-methyl-uridine (ncm ⁵Um), 5-carboxymethylaminomethyl-2′-O-methyl-uridine (cmnm ⁵Um), 3,2′-O-dimethyl-uridine (m³Um), 5-(isopentenylaminomethyl)-2′-O-methyl-uridine (inm⁵Um), 1-thio-uridine, deoxythymidine, 2′-F-ara-uridine, 2′-F-uridine, 2′-OH-ara-uridine, 5-(2-carbomethoxyvinyl) uridine, 5-[3-(1-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 (m³C), 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-1-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 (k²C), α-thio-cytidine, 2′-O-methyl-cytidine (Cm), 5,2′-O-dimethyl-cytidine (m⁵Cm), N4-acetyl-2′-O-methyl-cytidine (ac⁴Cm), N4,2′-O-dimethyl-cytidine (m⁴Cm), 5-formyl-2′-O-methyl-cytidine (f ⁵Cm), N4,N4,2′-O-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 (m¹A), 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, α-thio-adenosine, 2′-O-methyl-adenosine (Am), N⁶,2′-O-dimethyl-adenosine (m⁶Am), N⁶-Methyl-2′-deoxyadenosine, N6,N6,2′-O-trimethyl-adenosine (m⁶ ₂Am), 1,2′-O-dimethyl-adenosine (m¹Am), 2′-O-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)-adenosine.
• 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 (m¹I), wyosine (imG), methylwyosine (mimG), 4-demethyl-wyosine (imG-14), isowyosine (imG2), wybutosine (yW), peroxywybutosine (o₂yW), hydroxywybutosine (OHyW), undermodified hydroxywybutosine (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 (preQ₁), 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 (m⁷G), 6-thio-7-methyl-guanosine, 7-methyl-inosine, 6-methoxy-guanosine, 1-methyl-guanosine (m′G), N2-methyl-guanosine (m²G), N2,N2-dimethyl-guanosine (m² 2G), N2,7-dimethyl-guanosine (m²,7G), N2, N2,7-dimethyl-guanosine (m²,2,7G), 8-oxo-guanosine, 7-methyl-8-oxo-guanosine, 1-methyl-6- thio-guanosine, N2-methyl-6-thio-guanosine, N2,N2-dimethyl-6-thio-guanosine, α-thio-guanosine, 2′-O-methyl-guanosine (Gm), N2-methyl-2′-O-methyl-guanosine (m²Gm), N2,N2-dimethyl-2′-O-methyl-guanosine (m² 2Gm), 1-methyl-2′-O-methyl-guanosine (m′Gm), N2,7-dimethyl-2′-O-methyl-guanosine (m²,7Gm), 2′-O-methyl-inosine (Im), 1,2′-O-dimethyl-inosine (m′Im), O⁶-phenyl-2′-deoxyinosine, 2′-O-ribosylguanosine (phosphate) (Gr(p)), 1-thio-guanosine, O⁶-methyl-guanosine, O⁶-Methyl-2′-deoxyguanosine, 2′-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-1D, 2A-2F, 3A-3C, 4A-4E, 5A-5E, 6A-6B, 7A-7D, 8A-8D, 9, 10A-10D, 11A-11D, 12, 13A-13D, 14A-14C, 15A-15D, 16A-16E, 17A-17B, 18A-18C, 19A-19E, 20A-20C, 21A-21E, 22A-22E, 23A-23C, 24A-24D, 25A-25B, 26, 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′-O-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′-O-methyl, 2′-O-methoxyethyl, or 2′-Fluoro modified including, e.g., 2′-F or 2′-O-methyl, adenosine (A), 2′-F or 2′-O-methyl, cytidine (C), 2′-F or 2′-O-methyl, uridine (U), 2′-F or 2′-O-methyl, thymidine (T), 2′-F or 2′-O-methyl, guanosine (G), 2′-O-methoxyethyl-5-methyluridine (Teo), 2′-O-methoxyethyladenosine (Aeo), 2′-O-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 C1-6 alkylene or C1-6 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 O(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 α-L-threofuranosyl-(3′→2′)).
• Generally, gRNA molecules include the sugar group ribose, which is a 5-membered ring having an oxygen. Exemplary modified gRNAs can include, without limitation, replacement of the oxygen in ribose (e.g., with sulfur (S), selenium (Se), or alkylene, such as, e.g., methylene or ethylene); addition of a double bond (e.g., to replace ribose with cyclopentenyl or cyclohexenyl); ring contraction of ribose (e.g., to form a 4-membered ring of cyclobutane or oxetane); ring expansion of ribose (e.g., to form a 6- or 7-membered ring having an additional carbon or heteroatom, such as for example, anhydrohexitol, altritol, mannitol, cyclohexanyl, cyclohexenyl, and morpholino that also has a phosphoramidate backbone). Although the majority of sugar analog alterations are localized to the 2′ position, other sites are amenable to modification, including the 4′ position. In an embodiment, a gRNA comprises a 4′-S, 4′-Se or a 4′-C-aminomethyl-2′-O-Me modification.
• In some embodiments, deaza nucleotides, e.g., 7-deaza-adenosine, can be incorporated into the gRNA. In some embodiments, O- and N-alkylated nucleotides, e.g., N6-methyl adenosine, can be incorporated into the gRNA. In some embodiments, one or more or all of the nucleotides in a gRNA molecule are deoxynucleotides.
• miRNA Binding Sites
• microRNAs (or miRNAs) are naturally occurring cellular 19-25 nucleotide long noncoding RNAs. They bind to nucleic acid molecules having an appropriate miRNA binding site, e.g., in the 3′ UTR of an mRNA, and down-regulate gene expression. While not wishing to be bound by theory it is believed that the down regulation is either by reducing nucleic acid molecule stability or by inhibiting translation. An RNA species disclosed herein, e.g., an mRNA encoding Cas9 can comprise an miRNA binding site, e.g., in its 3′UTR. The miRNA binding site can be selected to promote down regulation of expression is a selected cell type. By way of example, the incorporation of a binding site for miR-122, a microRNA abundant in liver, can inhibit the expression of the gene of interest in the liver.
EXAMPLES
• The following Examples are merely illustrative and are not intended to limit the scope or content of the invention in any way.
Example 1: 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. H1 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., H1 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 U2OS. 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 T7E1-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 500-700 bp 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)½). 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 300-500 bp with the intended cut site placed asymmetrically. Following PCR, next generation sequencing adapters and barcodes (for example Illumina multiplex adapters and indexes) may be added to the ends of the amplicon, e.g., for use in high throughput sequencing (for example on an Illumina MiSeq). This method allows for detection of very low NHEJ rates.
Example 2: Assessment of Gene Targeting by NHEJ
• The gRNAs that induce the greatest levels of NHEJ in initial tests can be selected for further evaluation of gene targeting efficiency. In this case, cells are derived from disease subjects and, therefore, harbor the relevant mutation.
• Following transfection (usually 2-3 days post-transfection,) genomic DNA may be isolated from a bulk population of transfected cells and PCR may be used to amplify the target region. Following PCR, gene targeting efficiency to generate the desired mutations (either knockout of a target gene or removal of a target sequence motif) may be determined by sequencing. For Sanger sequencing, PCR amplicons may be 500-700 bp long. For next generation sequencing, PCR amplicons may be 300-500 bp long. If the goal is to knockout gene function, sequencing may be used to assess what percent of alleles have undergone NHEJ-induced indels that result in a frameshift or large deletion or insertion that would be expected to destroy gene function. If the goal is to remove a specific sequence motif, sequencing may be used to assess what percent of alleles have undergone NHEJ-induced deletions that span this sequence.
Example 3: Assessment of Gene Targeting by HDR
• The gRNAs that induce the greatest levels of NHEJ in initial tests can be selected for further evaluation of gene targeting efficiency. In this case, cells are derived from disease subjects and, therefore, harbor the relevant mutation.
• Following transfection (usually 2-3 days post-transfection,) genomic DNA may be isolated from a bulk population of transfected cells and PCR may be used to amplify the target region. Following PCR, gene targeting efficiency can be determined by several methods.
• Determination of gene targeting frequency involves measuring the percentage of alleles that have undergone homologous directed repair (HDR) with the exogenously provided donor template or endogenous genomic donor sequence and which therefore have incorporated the desired correction. If the desired HDR event creates or destroys a restriction enzyme site, the frequency of gene targeting may be determined by a RFLP assay. If no restriction site is created or destroyed, sequencing may be used to determine gene targeting frequency. If a RFLP assay is used, sequencing may still be used to verify the desired HDR event and ensure that no other mutations are present. If an exogenously provided donor template is employed, at least one of the primers is placed in the endogenous gene sequence outside of the region included in the homology arms, which prevents amplification of donor template still present in the cells. Therefore, the length of the homology arms present in the donor template may affect the length of the PCR amplicon. PCR amplicons can either span the entire donor region (both primers placed outside the homology arms) or they can span only part of the donor region and a single junction between donor and endogenous DNA (one internal and one external primer). If the amplicons span less than the entire donor region, two different PCRs should be used to amplify and sequence both the 5′ and the 3′ junction.
• If the PCR amplicon is short (less than 600 bp) it is possible to use next generation sequencing. Following PCR, next generation sequencing adapters and barcodes (for example Illumina multiplex adapters and indexes) may be added to the ends of the amplicon, e.g., for use in high throughput sequencing (for example on an Illumina MiSeq). This method allows for detection of very low gene targeting rates.
• If the PCR amplicon is too long for next generation sequencing, Sanger sequencing can be performed. For Sanger sequencing, purified PCR amplicons will be cloned into a plasmid backbone (for example, TOPO cloned using the LifeTech Zero Blunt® TOPO® cloning kit), transformed, miniprepped and sequenced.
• The same or similar assays described above can be used to measure the percentage of alleles that have undergone HDR with endogenous genomic donor sequence and which therefore have incorporated the desired correction.
Example 4: 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 BCL11A 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
  gRNA Name	Targeting Sequence	Size	Gene Region	SEQ ID NO
  BCL11A-2981W	GUGCUACUUAUACAAUUCAC	20	3′ of enhancer	16261
  BCL11A-2982W	GAAAAUACUUACUGUACUGC	20	3′ of enhancer	16262
  BCL11A-2983W	GGCUGUUUUGGAAUGUAGAG	20	5′ of enhancer	16263
  BCL11A-2984W	AUUCACUGGAAACCCUGUUA	20	3′ of enhancer	16264
  BCL11A-2985W	UACUGUACUGCAGGGGAAUU	20	3′ of enhancer	16265
  BCL11A-2986W	AAACUAUUUACAGCCAUAAC	20	3′ of enhancer	16266
  BCL11A-2987W	AAAUACUUACUGUACUGCAG	20	3′ of enhancer	16267
  BCL11A-2988W	CUAUUUACAGCCAUAAC	17	3′ of enhancer	16268
  BCL11A-2989W	CUACUUAUACAAUUCAC	17	3′ of enhancer	16269
  BCL11A-2990W	CACUGGAAACCCUGUUA	17	3′ of enhancer	16270
  BCL11A-2991W	UACUUACUGUACUGCAG	17	3′ of enhancer	16271
  BCL11A-2992W	UGUACUGCAGGGGAAUU	17	3′ of enhancer	16272
  BCL11A-2993W	AAUACUUACUGUACUGC	17	3′of enhancer	16273
  BCL11A-2994W	AUACUUACUGUACUGCA	17	3′ of enhancer	16274
  BCL11A-2995W	GAAUGUAGAGAGGCAGA	17	5′ of enhancer	16275
  BCL11A-2996W	GGAAUGUAGAGAGGCAG	17	5′ of enhancer	16276
  BCL11A-2997W	GUAAGUAUUUUCUUUCAUUG	20	3′ of enhancer	16277
  BCL11A-2998W	GUAAUUAAGAAAGCAGUGUA	20	5′ of enhancer	16278
  BCL11A-2999W	GUAUUUUCUUUCAUUGG	17	3′ of enhancer	16279
  BCL11A-32W	UGGCAUCCAGGUCACGCCAG	20	Exon 2	16280
  BCL11A-40W	GAUGCUUUUUUCAUCUCGAU	20	Exon 2	16281
  BCL11A-30W	GCAUCCAAUCCCGUGGAGGU	20	Exon 2	16282
  BCL11A-42W	UUUUCAUCUCGAUUGGUGAA	20	Exon 2	16283
  BCL11A-24W	CCAGAUGAACUUCCCAUUGG	20	Exon 2	16284
  BCL11A-53W	AGGAGGUCAUGAUCCCCUUC	20	Exon 2	16285
  BCL11A-79W	CAUCCAGGUCACGCCAG	17	Exon 2	16286
  BCL11A-90W	GCUUUUUUCAUCUCGAU	17	Exon 2	16287
  BCL11A-77W	UCCAAUCCCGUGGAGGU	17	Exon 2	16288
  BCL11A-92W	UCAUCUCGAUUGGUGAA	17	Exon 2	16289
  BCL11A-71W	GAUGAACUUCCCAUUGG	17	Exon 2	16290

• 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
  Primer Sequence	Exon
  TGCCTACATCTGATTCAGTGAGG (SEQ ID NO: 16291)	BCL11A exon 2 5′ primer
  TGCCTCATTGACAAATTTGCTC (SEQ ID NO: 16292)	BCL11A exon 2 3′ primer
  AGACCGTCTCTTTGGTGCAG (SEQ ID NO: 16293)	BCL11A 5′ enhancer 5′ primer
  GCAGTGGCTTTAGGCTGTTT (SEQ ID NO: 16294)	BCL11A 5′ enhancer 3′ primer
  GTGTGATCTCGGCTCACCAC (SEQ ID NO: 16295)	BCL11A 3′ enhancer 5′ primer
  CCCTGACTTTGGAGCTCAGC (SEQ ID NO: 16296)	BCL11A 3′ enhancer 3′ primer

• 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*(1-(1-(fraction cleaved)){circumflex over ( )}0.5). The results of this analysis are shown in FIG. 11 . The top performing gRNAs in this assay were BCL11A-2981, BCL11A-2983, BCL11A-2995, BCL11A-32, BCL11A-30, and BCL11A-71.
Example 5: 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 gRNAs were tested in 293 cells. Pair number 1 comprised BCL11A-2983W and BCL11A-2981W while Pair number 2 comprised BCL11A-2995W and BCL11A-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 BCL11A, 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.
Example 6: Gene Targeting of the HBB Locus by CRISPR/Cas9 to Investigate Repair Pathway Choice in Response to Different Types of DNA Lesions
• The CRISPR/Cas9 system was used to target the human HBB gene in the region of the sickle cell anemia-causing mutation.
• To examine how the nature of the targeted break affects the frequency of different DNA repair outcomes, blunt double-strand breaks, single-strand nicks, and dual-nicks in which the nicks are placed on opposite strands and leave either 3′ or 5′ overhangs of varying lengths, were introduced by utilizing the wild type Cas9 nuclease, as well as two different Cas9 nickases. Several different DNA repair outcomes including indel mutations resulting from non-homologous end-joining, homology-dependent repair (HDR) using the donor as a template, and HDR using the closely related HBD gene as an endogenous template, were characterized using either single-strand oligonucleotide (ssODN) or plasmid DNA donors. The frequency of these various repair outcomes under different conditions offer insight into the mechanisms of DNA repair and how it is impacted by the nature of the DNA break. The data also indicates a therapeutic approach in which correction of the sickle-cell mutation is efficiently mediated through HDR with either a donor template or with the HBD gene.
• In this study different gRNA for the HBB region that surrounds the nucleotides encoding the amino acid most commonly mutated in sickle cell disease had been tested in 293T cells with wild type Cas9 molecule. The gRNAs that induced similar high rates of NHEJ and had PAMs facing in opposite orientations were selected to test as pairs with Cas9 D10A and Cas9 N863A nickases.
• As shown in FIG. 14 , the gRNA pair 8/15 (“8gRNA”/“15gRNA” pair) was selected as one of the best pairs of gRNA. “8gRNA” has the targeting domain sequence of GUAACGGCAGACUUCUCCUC (SEQ ID NO: 388) and “15gRNA” has the targeting domain sequence of AAGGUGAACGUGGAUGAAGU (SEQ ID NO: 387). This pair of gRNAs in combination with the mutant Cas9 D10A would generate a 5′ overhang of 47 bp, and in combination with the mutant N863A would generate a 3′ overhang of 47 bp.
• In this Example, U20S cells were electroporated with 200 ng of each gRNA and 750 ng of plasmid that encodes wild type Cas9 or mutant Cas9. Cells were collected 6 days after electroporation and genomic DNA was extracted. PCR amplification of the HBB locus was performed and subcloned into a Topo Blunt Vector. For each condition in each experiment 96 colonies were sequenced with Sanger sequencing. In the experiments assessing HDR efficacy, cells were electroporated with 2.5 ug of single stranded oligo or double stranded oligo in addition to the gRNA and the Cas9-encoding plasmid.
• As shown in FIG. 15 , the total percentages of all editing events detected by Sanger sequencing of the HBB locus were similar using wild type Cas9 or Cas9 nickases (D10A, N863A).
• FIGS. 16A-16B show that a majority of the total gene editing events (about 3/4 of the total) were small deletions (<10 bp). This is consistent with the notion that wildtype Cas9 generates a blunt end which are preferentially repaired by canonical NHEJ. In contrast, deletions represented only about a quarter of the total events using either nickase (D10A or N863A). Moreover, larger deletions of ˜50 bp that can be mapped to the region between the two nickase sites were observed (FIG. 16A or 16C). The remaining gene-editing events were substantially different between the two nickases.
• As shown in FIG. 17A, in the case of Cas9 D10A nickase which leaves a 5′ protruding end, the lesion is mostly repaired through a mechanism defined as gene conversion. In gene conversion, the HBD locus will serve as a template to repair the HBB gene. HBD is a highly similar gene (92% identity with HBB) that does not carry the sickle-cell mutation (FIG. 17B). FIG. 18 shows that the majority of the HBD sequence that got incorporated in the HBB locus was in the region between the nickase cuts. In contrast, a low frequency of gene conversion was observed when the N863 nicase was used (FIG. 17A). In the case of Cas9 N863A nickase, a majority of the gene editing events were insertions in which the inserted part was a duplication of the overhangs (FIGS. 19A-19B).
• To test the effect that different lesions had on the engagement of HDR, a donor template was provided as a single strand oligo or as ds DNA donor. In both cases the length of the donor is approximately 170 bp with 60 bp of homology outside the nicks and with 8 mismatches (FIG. 20A). As shown in FIG. 20B, the Cas9 D10A nickase that resulted in a 5′ overhang gave a significantly higher rate of HDR, especially when using the upper stand as a single-strand oligo donor. FIG. 20C shows different forms of donors (dsDNA, upper stand, and lower strand) and there contribution to HDR.
• In summary, Cas9 nickases (D10A and N863A) showed comparable levels of efficacy compared to wildtype Cas9. Different DNA ends engage different repair pathways. The use of a wildtype Cas9 generates a blunt end, which are preferentially repaired by canonical NHEJ. Use of a Cas9 nickase with two gRNAs generates either 3′ or 5′ overhangs, which are not suitable substrates to be repaired by canonical NHEJ but can be repaired by alternative pathways.
• The 5′ protruding end was mostly repaired through a mechanism called gene conversion in which the HBB gene is repaired by using the HBD locus as a template. Use of nickase is advantageous to promote HDR. In the experiments in which a donor was provided, a significantly higher rate of HDR was observed using a nickase compared to the wildtype Cas9. The nature of the donor template also influences the outcome as HDR was preferentially observed when an SS Oligo was used.
Example 7: Assessment of Gene Targeting in Hematopoietic Stem Cells
• Transplantation of autologous CD34+ hematopoietic stem cells (HSCs, also known as hematopoietic stem/progenitor cells or HSPCs) genetically modified to correct the Sickle Cell Disease (SCD) mutation in the human β-hemoglobin gene (HBB) would prevent deformability (sickling) after deoxygenation in the erythrocyte progeny of corrected HSCs which could ameliorate symptoms associated with SCD. Genome editing with the CRISPR/Cas9 platform precisely alters endogenous gene targets by creating an indel at the targeted cut site that can lead to knock down of gene expression at the edited locus. In this Example, genome editing in the human K562 bone marrow erythroleukemia cell line, which serve as a proxy for HSCs and which can be predictive of genome editing in HSCs, were electroporated with Cas9 mRNA and gRNA HBB-8 and gRNA HBB-15 to induce gene editing at the human HBB locus.
• K562 cells were grown in RPMI media (Life Technologies) containing 10% fetal bovine serum (FBS). For the RNA electroporation, the Maxcyte GT device (maxcyte.com/) was used. S. pyogenes Cas9 mRNA and gRNA HBB-15 and gRNA HBB-8 were prepared by in vitro transcription using linearized plasmid DNA as templates and the Ambion mMessage mMachine® T7 Ultra Transcription kit (Life Technologies) according to the manufacturer's instructions. In this embodiment, both the Cas9 and gRNA were in vitro transcribed using a T7 polymerase. For example, a 5′ ARCA cap was added to both RNA species simultaneous to transcription while a polyA tail was added after transcription to the 3′ end of the RNA species by an E. coli polyA polymerase. Capped and tailed gRNA HBB-8 and gRNA HBB-15 were complexed at room temperature with S. pyogenes H-NLS-Cas9 protein at a molar ratio of ˜25:1 (gRNA:Cas9 protein) in a total of 30 pg RNP. Briefly, three million K562 cells were suspended in 100 μL Maxcyte EP buffer and transferred to the RNP solution (13 μL). In addition, K562 cells were electroporated with S. pyogenes Cas9 mRNA and each of the gRNA HBB-8 and gRNA HBB-15. For the mRNA/gRNA electroporation with the Maxcyte device, 10 μg of gRNA HBB-8 (or 10 μg of HBB gRNA HBB-15) were mixed with 10 μg of Cas9 mRNA. Four million K562 cells were suspended in 100 μL Maxcyte EP buffer and then transferred to the mRNA/gRNA solution (13 μL). K562 cells mixed with either RNP or RNA were electroporated with the Maxcyte GT device. At 48 hours after electroporation, K562 cells were enumerated by trypan blue exclusion and were determined to have >88% viability in the electroporated cell populations. Genomic DNA was extracted from K562 cells 48 hours after electroporation and HBB locus-specific PCR reactions were performed.
• In order to detect indels at the HBB locus, T7E1 assays were performed on HBB locus-specific PCR products that were amplified from genomic DNA samples from electroporated K562 cells and the percentage of indels detected at the HBB locus was calculated (FIG. 21 ).
• Co-delivery of 10 μg RNP which contains wild-type S. pyogenes Cas9 protein with HBB gRNA 8 or HBB gRNA 15 resulted in 26.8% and 16.1% indels, respectively, at the HBB locus in gDNA from K562 cells (molar ratio protein: gRNA 24:1). Co-delivery of Cas9 mRNA with gRNA HBB-8 or HBB-15 led to 66.9% and 29.5% indels at the HBB locus in gDNA from K562 cells (10 μg of each RNA/4 million cells). This example shows that delivery of Cas9 mRNA/gRNA and Cas9 RNPs leads to editing of the HBB locus in a relevant bone marrow derived hematopoietic cell line (K562 cells). Clinically, transplantation of autologous HSCs in which the HBB locus has been edited to correct the genetic mutation that causes red blood cell sickling could be used to ameliorate symptoms of SCD.
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 (21)

1-189. (canceled)

190. A gRNA molecule comprising a targeting domain which is complementary with a target domain from the HBB or BCL11A gene.

191. The gRNA molecule of claim 190, 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 an SCD target point position or an SCD target knockout position.

192. The gRNA molecule of claim 190, wherein said targeting domain is configured to target an early coding region or an enhancer region of the BCL11A gene.

193. The gRNA molecule of claim 190, wherein said targeting domain is configured to target a mutation in the HBB gene.

194. The gRNA molecule of claim 190, wherein said targeting domain is configured to target the promoter region of the BCL11A gene.

195. The gRNA molecule of claim 190, 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-1D, 2A-2F, 3A-3C, 4A-4E, 5A-5E, 6A-6B, 7A-7D, 8A-8D, 9, 10A-10D, 11A-11D, 12, 13A-13D, 14A-14C, 15A-15D, 16A-16E, 17A-17B, 18A-18C, 19A-19E, 20A-20C, 21A-21E, 22A-22E, 23A-23C, 24A-24D, 25A-25B, 26, or 31.

196. A nucleic acid that comprises a nucleotide sequence that encodes a gRNA molecule comprising a targeting domain that is complementary with an SCD target domain in the HBB gene or BCL11A gene.

197. The nucleic acid of claim 196 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 SCD target point position or the SCD target knockout position.

198. The nucleic acid of claim 196, wherein said targeting domain is configured to target an early coding region or an enhancer region of the BCL11A gene.

199. The nucleic acid of claim 196, wherein said targeting domain is configured to target a mutation in the HBB gene.

200. The nucleic acid of claim 196, wherein said targeting domain is configured to target the promoter region of the BCL11A gene.

201. The nucleic acid of claim 196, 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-1D, 2A-2F, 3A-3C, 4A-4E, 5A-5E, 6A-6B, 7A-7D, 8A-8D, 9, 10A-10D, 11A-11D, 12, 13A-13D, 14A-14C, 15A-15D, 16A-16E, 17A-17B, 18A-18C, 19A-19E, 20A-20C, 21A-21E, 22A-22E, 23A-23C, 24A-24D, 25A-25B, 26, or 31.

202. The nucleic acid of claim 196, further comprising a sequence that encodes a Cas9 molecule.

203. A method of altering a cell comprising contacting said cell with:

(a) a gRNA molecule comprising a targeting domain which is complementary with a target domain from the HBB or BCL11A gene; and

(b) a Cas9 molecule.

204. The method of claim 203, wherein said targeting domain is configured to target an early coding region or an enhancer region of the BCL11A gene.

205. The method of claim 203, wherein said targeting domain is configured to target a mutation in the HBB gene.

206. The method of claim 203, wherein said targeting domain is configured to target the promoter region of the BCL11A gene.

207. The method of claim 203, 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-1D, 2A-2F, 3A-3C, 4A-4E, 5A-5E, 6A-6B, 7A-7D, 8A-8D, 9, 10A-10D, 11A-11D, 12, 13A-13D, 14A-14C, 15A-15D, 16A-16E, 17A-17B, 18A-18C, 19A-19E, 20A-20C, 21A-21E, 22A-22E, 23A-23C, 24A-24D, 25A-25B, 26, or 31.

208. The method of claim 203, wherein said cell is selected from the group consisting of an erythroid cell, a bone marrow cell, and a stem cell.

209. The method of claim 203, wherein said contacting step is performed ex vivo.

Images