COMPOSITIONS COMPRISING AN RNA GUIDE TARGETING BCL11A AND USES THEREOF

SEQUENCE LISTING

The instant application contains a Sequence Listing which has been submitted electronically in ASCII format and is hereby incorporated by reference in its entirety. Said ASCII copy, created on Oct. 28, 2021, is named 51451-017WO3_Sequence_Listing_10_28_21_ST25, and is 682,314 bytes in size.

BACKGROUND

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR-associated (Cas) genes, collectively known as CRISPR-Cas or CRISPR/Cas systems, are adaptive immune systems in archaea and bacteria that defend particular species against foreign genetic elements.

SUMMARY OF THE INVENTION

It is against the above background that the present invention provides certain advantages and advancements over the prior art. Although this invention disclosed herein is not limited to specific advantages or functionalities, the invention provides a composition comprising an RNA guide, wherein the RNA guide comprises (i) a spacer sequence that is substantially complementary to a target sequence within a BCL11A gene and (ii) a direct repeat sequence; wherein the target sequence is adjacent to a protospacer adjacent motif (PAM) comprising the sequence 5′-NTTN-3′.

In one aspect of the composition, the target sequence is within exon 1, exon 2, exon 3, exon 4, or the enhancer region of the BCL11A gene.

In another aspect of the composition, the BCL11A gene comprises the sequence of SEQ ID NO: 2635, the reverse complement of SEQ ID NO: 2635, a variant of SEQ ID NO: 2635, or the reverse complement of a variant of SEQ ID NO: 2635.

In another aspect of the composition, the spacer sequence comprises: a. nucleotide 1 through nucleotide 16 of a sequence that is at least 90% identical to a sequence of any one of SEQ ID NOs: 1322-2632; b. nucleotide 1 through nucleotide 17 of a sequence that is at least 90% identical to a sequence of any one of SEQ ID NOs: 1322-2632; c. nucleotide 1 through nucleotide 18 of a sequence that is at least 90% identical to a sequence of any one of SEQ ID NOs: 1322-2632; d. nucleotide 1 through nucleotide 19 of a sequence that is at least 90% identical to a sequence of any one of SEQ ID NOs: 1322-2632; e. nucleotide 1 through nucleotide 20 of a sequence that is at least 90% identical to a sequence of any one of SEQ ID NOs: 1322-2632; f. nucleotide 1 through nucleotide 21 of a sequence that is at least 90% identical to a sequence of any one of SEQ ID NOs: 1322-2632; g. nucleotide 1 through nucleotide 22 of a sequence that is at least 90% identical to a sequence of any one of SEQ ID NOs: 1322-2632; h. nucleotide 1 through nucleotide 23 of a sequence that is at least 90% identical to a sequence of any one of SEQ ID NOs: 1322-2632; i. nucleotide 1 through nucleotide 24 of a sequence that is at least 90% identical to a sequence of any one of SEQ ID NOs: 1322-2632; j. nucleotide 1 through nucleotide 25 of a sequence that is at least 90% identical to a sequence of any one of SEQ ID NOs: 1322-2632; k. nucleotide 1 through nucleotide 26 of a sequence that is at least 90% identical to a sequence of any one of SEQ ID NOs: 1322-2632; 1. nucleotide 1 through nucleotide 27 of a sequence that is at least 90% identical to a sequence of any one of SEQ ID NOs: 1322-2632; m. nucleotide 1 through nucleotide 28 of a sequence that is at least 90% identical to a sequence of any one of SEQ ID NOs: 1322-2632; n. nucleotide 1 through nucleotide 29 of a sequence that is at least 90% identical to a sequence of any one of SEQ ID NOs: 1322-1425 and 1427-2632; or o. nucleotide 1 through nucleotide 30 of a sequence that is at least 90% identical to a sequence of any one of SEQ ID NOs: 1322-1425 and 1427-2632.

In another aspect of the composition, the spacer sequence comprises: a. nucleotide 1 through nucleotide 16 of any one of SEQ ID NOs: 1322-2632; b. nucleotide 1 through nucleotide 17 of any one of SEQ ID NOs: 1322-2632; c. nucleotide 1 through nucleotide 18 of any one of SEQ ID NOs: 1322-2632; d. nucleotide 1 through nucleotide 19 of any one of SEQ ID NOs: 1322-2632; e. nucleotide 1 through nucleotide 20 of any one of SEQ ID NOs: 1322-2632; f. nucleotide 1 through nucleotide 21 of any one of SEQ ID NOs: 1322-2632; g. nucleotide 1 through nucleotide 22 of any one of SEQ ID NOs: 1322-2632; h. nucleotide 1 through nucleotide 23 of any one of SEQ ID NOs: 1322-2632; i. nucleotide 1 through nucleotide 24 of any one of SEQ ID NOs: 1322-2632; j. nucleotide 1 through nucleotide 25 of any one of SEQ ID NOs: 1322-2632; k. nucleotide 1 through nucleotide 26 of any one of SEQ ID NOs: 1322-2632; 1. nucleotide 1 through nucleotide 27 of any one of SEQ ID NOs: 1322-2632; m. nucleotide 1 through nucleotide 28 of any one of SEQ ID NOs: 1322-2632; n. nucleotide 1 through nucleotide 29 of any one of SEQ ID NOs: 1322-1425 and 1427-2632; or o. nucleotide 1 through nucleotide 30 of any one of SEQ ID NOs: 1322-1425 and 1427-2632.

In another aspect of the composition, the direct repeat comprises: a. nucleotide 1 through nucleotide 36 of a sequence that is at least 90% identical to a sequence of any one of SEQ ID NOs: 1-8; b. nucleotide 2 through nucleotide 36 of a sequence that is at least 90% identical to a sequence of any one of SEQ ID NOs: 1-8; c. nucleotide 3 through nucleotide 36 of a sequence that is at least 90% identical to a sequence of any one of SEQ ID NOs: 1-8; d. nucleotide 4 through nucleotide 36 of a sequence that is at least 90% identical to a sequence of any one of SEQ ID NOs: 1-8; e. nucleotide 5 through nucleotide 36 of a sequence that is at least 90% identical to a sequence of any one of SEQ ID NOs: 1-8; f. nucleotide 6 through nucleotide 36 of a sequence that is at least 90% identical to a sequence of any one of SEQ ID NOs: 1-8; g. nucleotide 7 through nucleotide 36 of a sequence that is at least 90% identical to a sequence of any one of SEQ ID NOs: 1-8; h. nucleotide 8 through nucleotide 36 of a sequence that is at least 90% identical to a sequence of any one of SEQ ID NOs: 1-8; i. nucleotide 9 through nucleotide 36 of a sequence that is at least 90% identical to a sequence of any one of SEQ ID NOs: 1-8; j. nucleotide 10 through nucleotide 36 of a sequence that is at least 90% identical to a sequence of any one of SEQ ID NOs: 1-8; k. nucleotide 11 through nucleotide 36 of a sequence that is at least 90% identical to a sequence of any one of SEQ ID NOs: 1-8; 1. nucleotide 12 through nucleotide 36 of a sequence that is at least 90% identical to a sequence of any one of SEQ ID NOs: 1-8; m. nucleotide 13 through nucleotide 36 of a sequence that is at least 90% identical to a sequence of any one of SEQ ID NOs: 1-8; n. nucleotide 14 through nucleotide 36 of a sequence that is at least 90% identical to a sequence of any one of SEQ ID NOs: 1-8; o. nucleotide 1 through nucleotide 34 of a sequence that is at least 90% identical to a sequence of SEQ ID NO: 9; p. nucleotide 2 through nucleotide 34 of a sequence that is at least 90% identical to a sequence of SEQ ID NO: 9; q. nucleotide 3 through nucleotide 34 of a sequence that is at least 90% identical to a sequence of SEQ ID NO: 9; r. nucleotide 4 through nucleotide 34 of a sequence that is at least 90% identical to a sequence of SEQ ID NO: 9; s. nucleotide 5 through nucleotide 34 of a sequence that is at least 90% identical to a sequence of SEQ ID NO: 9; t. nucleotide 6 through nucleotide 34 of a sequence that is at least 90% identical to a sequence of SEQ ID NO: 9; u. nucleotide 7 through nucleotide 34 of a sequence that is at least 90% identical to a sequence of SEQ ID NO: 9; v. nucleotide 8 through nucleotide 34 of a sequence that is at least 90% identical to a sequence of SEQ ID NO: 9; w. nucleotide 9 through nucleotide 34 of a sequence that is at least 90% identical to a sequence of SEQ ID NO: 9; x. nucleotide 10 through nucleotide 34 of a sequence that is at least 90% identical to a sequence of SEQ ID NO: 9; y. nucleotide 11 through nucleotide 34 of a sequence that is at least 90% identical to a sequence of SEQ ID NO: 9; z. nucleotide 12 through nucleotide 34 of a sequence that is at least 90% identical to a sequence of SEQ ID NO: 9; or aa. a sequence that is at least 90% identical to a sequence of SEQ ID NO: 10 or a portion thereof.

In another aspect of the composition, the direct repeat comprises: a. nucleotide 1 through nucleotide 36 of any one of SEQ ID NOs: 1-8; b. nucleotide 2 through nucleotide 36 of any one of SEQ ID NOs: 1-8; c. nucleotide 3 through nucleotide 36 of any one of SEQ ID NOs: 1-8; d. nucleotide 4 through nucleotide 36 of any one of SEQ ID NOs: 1-8; e. nucleotide 5 through nucleotide 36 of any one of SEQ ID NOs: 1-8; f. nucleotide 6 through nucleotide 36 of any one of SEQ ID NOs: 1-8; g. nucleotide 7 through nucleotide 36 of any one of SEQ ID NOs: 1-8; h. nucleotide 8 through nucleotide 36 of any one of SEQ ID NOs: 1-8; i. nucleotide 9 through nucleotide 36 of any one of SEQ ID NOs: 1-8; j. nucleotide 10 through nucleotide 36 of any one of SEQ ID NOs: 1-8; k. nucleotide 11 through nucleotide 36 of any one of SEQ ID NOs: 1-8; 1. nucleotide 12 through nucleotide 36 of any one of SEQ ID NOs: 1-8; m. nucleotide 13 through nucleotide 36 of any one of SEQ ID NOs: 1-8; n. nucleotide 14 through nucleotide 36 of any one of SEQ ID NOs: 1-8; o. nucleotide 1 through nucleotide 34 of SEQ ID NO: 9; p. nucleotide 2 through nucleotide 34 of SEQ ID NO: 9; q. nucleotide 3 through nucleotide 34 of SEQ ID NO: 9; r. nucleotide 4 through nucleotide 34 of SEQ ID NO: 9; s. nucleotide 5 through nucleotide 34 of SEQ ID NO: 9; t. nucleotide 6 through nucleotide 34 of SEQ ID NO: 9; u. nucleotide 7 through nucleotide 34 of SEQ ID NO: 9; v. nucleotide 8 through nucleotide 34 of SEQ ID NO: 9; w. nucleotide 9 through nucleotide 34 of SEQ ID NO: 9; x. nucleotide 10 through nucleotide 34 of SEQ ID NO: 9; y. nucleotide 11 through nucleotide 34 of SEQ ID NO: 9; z. nucleotide 12 through nucleotide 34 of SEQ ID NO: 9; or aa. SEQ ID NO: 10 or a portion thereof.

In another aspect of the composition, the direct repeat comprises: a. nucleotide 1 through nucleotide 36 of any one of SEQ ID NOs: 2652-2669; b. nucleotide 2 through nucleotide 36 of any one of SEQ ID NOs: 2652-2669; c. nucleotide 3 through nucleotide 36 of any one of SEQ ID NOs: 2652-2669; d. nucleotide 4 through nucleotide 36 of any one of SEQ ID NOs: 2652-2669; e. nucleotide 5 through nucleotide 36 of any one of SEQ ID NOs: 2652-2669; f. nucleotide 6 through nucleotide 36 of any one of SEQ ID NOs: 2652-2669; g. nucleotide 7 through nucleotide 36 of any one of SEQ ID NOs: 2652-2669; h. nucleotide 8 through nucleotide 36 of any one of SEQ ID NOs: 2652-2669; i. nucleotide 9 through nucleotide 36 of any one of SEQ ID NOs: 2652-2669; j. nucleotide 10 through nucleotide 36 of any one of SEQ ID NOs: 2652-2669; k. nucleotide 11 through nucleotide 36 of any one of SEQ ID NOs: 2652-2669; 1. nucleotide 12 through nucleotide 36 of any one of SEQ ID NOs: 2652-2669; m. nucleotide 13 through nucleotide 36 of any one of SEQ ID NOs: 2652-2669; n. nucleotide 14 through nucleotide 36 of any one of SEQ ID NOs: 2652-2669; or o. SEQ ID NO: 2670 or a portion thereof.

In another aspect of the composition, the direct repeat comprises: a. nucleotide 1 through nucleotide 36 of a sequence that is at least 90% identical to SEQ ID NO: 2671; b. nucleotide 2 through nucleotide 36 of a sequence that is at least 90% identical to SEQ ID NO: 2671; c. nucleotide 3 through nucleotide 36 of a sequence that is at least 90% identical to SEQ ID NO: 2671; d. nucleotide 4 through nucleotide 36 of a sequence that is at least 90% identical to SEQ ID NO: 2671; e. nucleotide 5 through nucleotide 36 of a sequence that is at least 90% identical to SEQ ID NO: 2671; f. nucleotide 6 through nucleotide 36 of a sequence that is at least 90% identical to SEQ ID NO: 2671; g. nucleotide 7 through nucleotide 36 of a sequence that is at least 90% identical to SEQ ID NO: 2671; h. nucleotide 8 through nucleotide 36 of a sequence that is at least 90% identical to SEQ ID NO: 2671; i. nucleotide 9 through nucleotide 36 of a sequence that is at least 90% identical to SEQ ID NO: 2671; j. nucleotide 10 through nucleotide 36 of a sequence that is at least 90% identical to SEQ ID NO: 2671; k. nucleotide 11 through nucleotide 36 of a sequence that is at least 90% identical to SEQ ID NO: 2671; 1. nucleotide 12 through nucleotide 36 of a sequence that is at least 90% identical to SEQ ID NO: 2671; m. nucleotide 13 through nucleotide 36 of a sequence that is at least 90% identical to SEQ ID NO: 2671; n. nucleotide 14 through nucleotide 36 of a sequence that is at least 90% identical to SEQ ID NO: 2671; or o. a sequence that is at least 90% identical to a sequence of SEQ ID NO: 2672 or SEQ ID NO: 2673 or a portion thereof.

In another aspect of the composition, the direct repeat comprises: a. nucleotide 1 through nucleotide 36 of SEQ ID NO: 2671; b. nucleotide 2 through nucleotide 36 of SEQ ID NO: 2671; c. nucleotide 3 through nucleotide 36 of SEQ ID NO: 2671; d. nucleotide 4 through nucleotide 36 of SEQ ID NO: 2671; e. nucleotide 5 through nucleotide 36 of SEQ ID NO: 2671; f. nucleotide 6 through nucleotide 36 of SEQ ID NO: 2671; g. nucleotide 7 through nucleotide 36 of SEQ ID NO: 2671; h. nucleotide 8 through nucleotide 36 of SEQ ID NO: 2671; i. nucleotide 9 through nucleotide 36 of SEQ ID NO: 2671; j. nucleotide 10 through nucleotide 36 of SEQ ID NO: 2671; k. nucleotide 11 through nucleotide 36 of SEQ ID NO: 2671; 1. nucleotide 12 through nucleotide 36 of SEQ ID NO: 2671; m. nucleotide 13 through nucleotide 36 of SEQ ID NO: 2671; n. nucleotide 14 through nucleotide 36 of SEQ ID NO: 2671; or o. SEQ ID NO: 2672 or SEQ ID NO: 2673 or a portion thereof.

In another aspect of the composition, the direct repeat comprises: a. nucleotide 1 through nucleotide 36 of a sequence that is at least 90% identical to a sequence of SEQ ID NO: 2674 or SEQ ID NO: 2675; b. nucleotide 2 through nucleotide 36 of a sequence that is at least 90% identical to a sequence of SEQ ID NO: 2674 or SEQ ID NO: 2675; c. nucleotide 3 through nucleotide 36 of a sequence that is at least 90% identical to a sequence of SEQ ID NO: 2674 or SEQ ID NO: 2675; d. nucleotide 4 through nucleotide 36 of a sequence that is at least 90% identical to a sequence of SEQ ID NO: 2674 or SEQ ID NO: 2675; e. nucleotide 5 through nucleotide 36 of a sequence that is at least 90% identical to a sequence of SEQ ID NO: 2674 or SEQ ID NO: 2675; f. nucleotide 6 through nucleotide 36 of a sequence that is at least 90% identical to a sequence of SEQ ID NO: 2674 or SEQ ID NO: 2675; g. nucleotide 7 through nucleotide 36 of a sequence that is at least 90% identical to a sequence of SEQ ID NO: 2674 or SEQ ID NO: 2675; h. nucleotide 8 through nucleotide 36 of a sequence that is at least 90% identical to a sequence of SEQ ID NO: 2674 or SEQ ID NO: 2675; i. nucleotide 9 through nucleotide 36 of a sequence that is at least 90% identical to a sequence of SEQ ID NO: 2674 or SEQ ID NO: 2675; j. nucleotide 10 through nucleotide 36 of a sequence that is at least 90% identical to a sequence of SEQ ID NO: 2674 or SEQ ID NO: 2675; k. nucleotide 11 through nucleotide 36 of a sequence that is at least 90% identical to a sequence of SEQ ID NO: 2674 or SEQ ID NO: 2675; 1. nucleotide 12 through nucleotide 36 of a sequence that is at least 90% identical to a sequence of SEQ ID NO: 2674 or SEQ ID NO: 2675; m. nucleotide 13 through nucleotide 36 of a sequence that is at least 90% identical to a sequence of SEQ ID NO: 2674 or SEQ ID NO: 2675; n. nucleotide 14 through nucleotide 36 of a sequence that is at least 90% identical to a sequence of SEQ ID NO: 2674 or SEQ ID NO: 2675; o. nucleotide 15 through nucleotide 36 of a sequence that is at least 90% identical to a sequence of SEQ ID NO: 2674 or SEQ ID NO: 2675; or p. a sequence that is at least 90% identical to a sequence of SEQ ID NO: 2676 or a portion thereof.

In another aspect of the composition, the direct repeat comprises: a. nucleotide 1 through nucleotide 36 of SEQ ID NO: 2674 or SEQ ID NO: 2675; b. nucleotide 2 through nucleotide 36 of SEQ ID NO: 2674 or SEQ ID NO: 2675; c. nucleotide 3 through nucleotide 36 of SEQ ID NO: 2674 or SEQ ID NO: 2675; d. nucleotide 4 through nucleotide 36 of SEQ ID NO: 2674 or SEQ ID NO: 2675; e. nucleotide 5 through nucleotide 36 of SEQ ID NO: 2674 or SEQ ID NO: 2675; f. nucleotide 6 through nucleotide 36 of SEQ ID NO: 2674 or SEQ ID NO: 2675; g. nucleotide 7 through nucleotide 36 of SEQ ID NO: 2674 or SEQ ID NO: 2675; h. nucleotide 8 through nucleotide 36 of SEQ ID NO: 2674 or SEQ ID NO: 2675; i. nucleotide 9 through nucleotide 36 of SEQ ID NO: 2674 or SEQ ID NO: 2675; j. nucleotide 10 through nucleotide 36 of SEQ ID NO: 2674 or SEQ ID NO: 2675; k. nucleotide 11 through nucleotide 36 of SEQ ID NO: 2674 or SEQ ID NO: 2675; 1. nucleotide 12 through nucleotide 36 of SEQ ID NO: 2674 or SEQ ID NO: 2675; m. nucleotide 13 through nucleotide 36 of SEQ ID NO: 2674 or SEQ ID NO: 2675; n. nucleotide 14 through nucleotide 36 of SEQ ID NO: 2674 or SEQ ID NO: 2675; o. nucleotide 15 through nucleotide 36 of SEQ ID NO: 2674 or SEQ ID NO: 2675; or p. SEQ ID NO: 2676 or a portion thereof.

In another aspect of the composition, the spacer sequence is substantially complementary to the complement of a sequence of any one of SEQ ID NOs: 11-1321.

In another aspect of the composition, the PAM comprises the sequence 5′-ATTA-3′, 5′-ATTT-3′, 5′-ATTG-3′, 5′-ATTC-3′, 5′-TTTA-3′, 5′-TTTT-3′, 5′-TTTG-3′, 5′-TTTC-3′, 5′-GTTA-3′, 5′-GTTT-3′, 5′-GTTG-3′, 5′-GTTC-3′, 5′-CTTA-3′, 5′-CTTT-3′, 5′-CTTG-3′, or 5′-CTTC-3′.

In another aspect of the composition, the target sequence is immediately adjacent to the PAM sequence.

In another aspect of the composition, the composition further comprises a Cas12i polypeptide.

In another aspect of the composition, the Cas12i polypeptide is: a. a Cas12i2 polypeptide comprising a sequence that is at least 90% identical to the sequence of SEQ ID NO: 2634, SEQ ID NO: 2641, SEQ ID NO: 2642, SEQ ID NO: 2643, SEQ ID NO: 2644, or SEQ ID NO: 2645; b. a Cas12i4 polypeptide comprising a sequence that is at least 90% identical to the sequence of SEQ ID NO: 2647, SEQ ID NO: 2648, or SEQ ID NO: 2649; c. a Cas12i1 polypeptide comprising a sequence that is at least 90% identical to the sequence of SEQ ID NO: 2650; or d. a Cas12i3 polypeptide comprising a sequence that is at least 90% identical to the sequence of SEQ ID NO: 2651.

In another aspect of the composition, the Cas12i polypeptide is: a. a Cas12i2 polypeptide comprising a sequence of SEQ ID NO: 2634, SEQ ID NO: 2641, SEQ ID NO: 2642, SEQ ID NO: 2643, SEQ ID NO: 2644, or SEQ ID NO: 2645; b. a Cas12i4 polypeptide comprising a sequence of SEQ ID NO: 2647, SEQ ID NO: 2648, or SEQ ID NO: 2649; c. a Cas12i1 polypeptide comprising a sequence of SEQ ID NO: 2650; or d. a Cas12i3 polypeptide comprising a sequence of SEQ ID NO: 2651.

In another aspect of the composition, the RNA guide and the Cas12i polypeptide form a ribonucleoprotein complex.

In another aspect of the composition, the ribonucleoprotein complex binds a target nucleic acid.

In another aspect of the composition, the composition is present within a cell.

In another aspect of the composition, the RNA guide and the Cas12i polypeptide are encoded in a vector, e.g., expression vector. In another aspect of the composition, the RNA guide and the Cas12i polypeptide are encoded in a single vector or the RNA guide is encoded in a first vector and the Cas12i polypeptide is encoded in a second vector.

The invention further provides a vector system comprising one or more vectors encoding an RNA guide disclosed herein and a Cas12i polypeptide. In an embodiment, the vector system comprises a first vector encoding an RNA guide disclosed herein and a second vector encoding a Cas12i polypeptide. The vectors may be expression vectors.

The invention further provides a composition comprising an RNA guide and a Cas12i polypeptide, wherein the RNA guide comprises (i) a spacer sequence that is substantially complementary to a target sequence within a BCL11A gene and (ii) a direct repeat sequence.

In one aspect of the composition, the target sequence is within exon 1, exon 2, exon 3, exon 4, or the enhancer region of the BCL11A gene.

In another aspect of the composition, the spacer sequence is substantially complementary to the complement of a sequence of any one of SEQ ID NOs: 11-1321.

In another aspect of the composition, the target sequence is adjacent to a protospacer adjacent motif (PAM) comprising the sequence 5′-NTTN-3′.

In another aspect of the composition, the target sequence is immediately adjacent to the PAM sequence.

In another aspect of the composition, the target sequence is within 1, 2, 3, 4, or 5 nucleotides of the PAM sequence.

In another aspect of the composition, the RNA guide and the Cas12i polypeptide form a ribonucleoprotein complex.

In another aspect of the composition, the ribonucleoprotein complex binds a target nucleic acid.

In another aspect of the composition, the composition is present within a cell.

The invention yet further provides an RNA guide comprising (i) a spacer sequence that is substantially complementary to a target sequence within a BCL11A gene and (ii) a direct repeat sequence.

In one aspect of the RNA guide, the target sequence is within exon 1, exon 2, exon 3, exon 4, or the enhancer region of the BCL11A gene.

In another aspect of the RNA guide, the BCL11A gene comprises the sequence of SEQ ID NO: 2635, the reverse complement of SEQ ID NO: 2635, a variant of SEQ ID NO: 2635, or the reverse complement of a variant of SEQ ID NO: 2635.

In another aspect of the RNA guide, the spacer sequence comprises: a. nucleotide 1 through nucleotide 16 of a sequence that is at least 90% identical to a sequence of any one of SEQ ID NOs: 1322-2632; b. nucleotide 1 through nucleotide 17 of a sequence that is at least 90% identical to a sequence of any one of SEQ ID NOs: 1322-2632; c. nucleotide 1 through nucleotide 18 of a sequence that is at least 90% identical to a sequence of any one of SEQ ID NOs: 1322-2632; d. nucleotide 1 through nucleotide 19 of a sequence that is at least 90% identical to a sequence of any one of SEQ ID NOs: 1322-2632; e. nucleotide 1 through nucleotide 20 of a sequence that is at least 90% identical to a sequence of any one of SEQ ID NOs: 1322-2632; f. nucleotide 1 through nucleotide 21 of a sequence that is at least 90% identical to a sequence of any one of SEQ ID NOs: 1322-2632; g. nucleotide 1 through nucleotide 22 of a sequence that is at least 90% identical to a sequence of any one of SEQ ID NOs: 1322-2632; h. nucleotide 1 through nucleotide 23 of a sequence that is at least 90% identical to a sequence of any one of SEQ ID NOs: 1322-2632; i. nucleotide 1 through nucleotide 24 of a sequence that is at least 90% identical to a sequence of any one of SEQ ID NOs: 1322-2632; j. nucleotide 1 through nucleotide 25 of a sequence that is at least 90% identical to a sequence of any one of SEQ ID NOs: 1322-2632; k. nucleotide 1 through nucleotide 26 of a sequence that is at least 90% identical to a sequence of any one of SEQ ID NOs: 1322-2632; 1. nucleotide 1 through nucleotide 27 of a sequence that is at least 90% identical to a sequence of any one of SEQ ID NOs: 1322-2632; m. nucleotide 1 through nucleotide 28 of a sequence that is at least 90% identical to a sequence of any one of SEQ ID NOs: 1322-2632; n. nucleotide 1 through nucleotide 29 of a sequence that is at least 90% identical to a sequence of any one of SEQ ID NOs: 1322-1425 and 1427-2632; or o. nucleotide 1 through nucleotide 30 of a sequence that is at least 90% identical to a sequence of any one of SEQ ID NOs: 1322-1425 and 1427-2632.

In another aspect of the RNA guide, the direct repeat comprises: a. nucleotide 1 through nucleotide 36 of a sequence that is at least 90% identical to a sequence of any one of SEQ ID NOs: 1-8; b. nucleotide 2 through nucleotide 36 of a sequence that is at least 90% identical to a sequence of any one of SEQ ID NOs: 1-8; c. nucleotide 3 through nucleotide 36 of a sequence that is at least 90% identical to a sequence of any one of SEQ ID NOs: 1-8; d. nucleotide 4 through nucleotide 36 of a sequence that is at least 90% identical to a sequence of any one of SEQ ID NOs: 1-8; e. nucleotide 5 through nucleotide 36 of a sequence that is at least 90% identical to a sequence of any one of SEQ ID NOs: 1-8; f. nucleotide 6 through nucleotide 36 of a sequence that is at least 90% identical to a sequence of any one of SEQ ID NOs: 1-8; g. nucleotide 7 through nucleotide 36 of a sequence that is at least 90% identical to a sequence of any one of SEQ ID NOs: 1-8; h. nucleotide 8 through nucleotide 36 of a sequence that is at least 90% identical to a sequence of any one of SEQ ID NOs: 1-8; i. nucleotide 9 through nucleotide 36 of a sequence that is at least 90% identical to a sequence of any one of SEQ ID NOs: 1-8; j. nucleotide 10 through nucleotide 36 of a sequence that is at least 90% identical to a sequence of any one of SEQ ID NOs: 1-8; k. nucleotide 11 through nucleotide 36 of a sequence that is at least 90% identical to a sequence of any one of SEQ ID NOs: 1-8; 1. nucleotide 12 through nucleotide 36 of a sequence that is at least 90% identical to a sequence of any one of SEQ ID NOs: 1-8; m. nucleotide 13 through nucleotide 36 of a sequence that is at least 90% identical to a sequence of any one of SEQ ID NOs: 1-8; n. nucleotide 14 through nucleotide 36 of a sequence that is at least 90% identical to a sequence of any one of SEQ ID NOs: 1-8; o. nucleotide 1 through nucleotide 34 of a sequence that is at least 90% identical to a sequence of SEQ ID NO: 9; p. nucleotide 2 through nucleotide 34 of a sequence that is at least 90% identical to a sequence of SEQ ID NO: 9; q. nucleotide 3 through nucleotide 34 of a sequence that is at least 90% identical to a sequence of SEQ ID NO: 9; r. nucleotide 4 through nucleotide 34 of a sequence that is at least 90% identical to a sequence of SEQ ID NO: 9; s. nucleotide 5 through nucleotide 34 of a sequence that is at least 90% identical to a sequence of SEQ ID NO: 9; t. nucleotide 6 through nucleotide 34 of a sequence that is at least 90% identical to a sequence of SEQ ID NO: 9; u. nucleotide 7 through nucleotide 34 of a sequence that is at least 90% identical to a sequence of SEQ ID NO: 9; v. nucleotide 8 through nucleotide 34 of a sequence that is at least 90% identical to a sequence of SEQ ID NO: 9; w. nucleotide 9 through nucleotide 34 of a sequence that is at least 90% identical to a sequence of SEQ ID NO: 9; x. nucleotide 10 through nucleotide 34 of a sequence that is at least 90% identical to a sequence of SEQ ID NO: 9; y. nucleotide 11 through nucleotide 34 of a sequence that is at least 90% identical to a sequence of SEQ ID NO: 9; z. nucleotide 12 through nucleotide 34 of a sequence that is at least 90% identical to a sequence of SEQ ID NO: 9; or aa. a sequence that is at least 90% identical to a sequence of SEQ ID NO: 10 or a portion thereof.

In another aspect of the RNA guide, the direct repeat comprises: a. nucleotide 1 through nucleotide 36 of any one of SEQ ID NOs: 1-8; b. nucleotide 2 through nucleotide 36 of any one of SEQ ID NOs: 1-8; c. nucleotide 3 through nucleotide 36 of any one of SEQ ID NOs: 1-8; d. nucleotide 4 through nucleotide 36 of any one of SEQ ID NOs: 1-8; e. nucleotide 5 through nucleotide 36 of any one of SEQ ID NOs: 1-8; f. nucleotide 6 through nucleotide 36 of any one of SEQ ID NOs: 1-8; g. nucleotide 7 through nucleotide 36 of any one of SEQ ID NOs: 1-8; h. nucleotide 8 through nucleotide 36 of any one of SEQ ID NOs: 1-8; i. nucleotide 9 through nucleotide 36 of any one of SEQ ID NOs: 1-8; j. nucleotide 10 through nucleotide 36 of any one of SEQ ID NOs: 1-8; k. nucleotide 11 through nucleotide 36 of any one of SEQ ID NOs: 1-8; 1. nucleotide 12 through nucleotide 36 of any one of SEQ ID NOs: 1-8; m. nucleotide 13 through nucleotide 36 of any one of SEQ ID NOs: 1-8; n. nucleotide 14 through nucleotide 36 of any one of SEQ ID NOs: 1-8; o. nucleotide 1 through nucleotide 34 of SEQ ID NO: 9; p. nucleotide 2 through nucleotide 34 of SEQ ID NO: 9; q. nucleotide 3 through nucleotide 34 of SEQ ID NO: 9; r. nucleotide 4 through nucleotide 34 of SEQ ID NO: 9; s. nucleotide 5 through nucleotide 34 of SEQ ID NO: 9; t. nucleotide 6 through nucleotide 34 of SEQ ID NO: 9; u. nucleotide 7 through nucleotide 34 of SEQ ID NO: 9; v. nucleotide 8 through nucleotide 34 of SEQ ID NO: 9; w. nucleotide 9 through nucleotide 34 of SEQ ID NO: 9; x. nucleotide 10 through nucleotide 34 of SEQ ID NO: 9; y. nucleotide 11 through nucleotide 34 of SEQ ID NO: 9; z. nucleotide 12 through nucleotide 34 of SEQ ID NO: 9; or aa. SEQ ID NO: 10 or a portion thereof.

In another aspect of the RNA guide, the direct repeat comprises: a. nucleotide 1 through nucleotide 36 of any one of SEQ ID NOs: 2652-2669; b. nucleotide 2 through nucleotide 36 of any one of SEQ ID NOs: 2652-2669; c. nucleotide 3 through nucleotide 36 of any one of SEQ ID NOs: 2652-2669; d. nucleotide 4 through nucleotide 36 of any one of SEQ ID NOs: 2652-2669; e. nucleotide 5 through nucleotide 36 of any one of SEQ ID NOs: 2652-2669; f. nucleotide 6 through nucleotide 36 of any one of SEQ ID NOs: 2652-2669; g. nucleotide 7 through nucleotide 36 of any one of SEQ ID NOs: 2652-2669; h. nucleotide 8 through nucleotide 36 of any one of SEQ ID NOs: 2652-2669; i. nucleotide 9 through nucleotide 36 of any one of SEQ ID NOs: 2652-2669; j. nucleotide 10 through nucleotide 36 of any one of SEQ ID NOs: 2652-2669; k. nucleotide 11 through nucleotide 36 of any one of SEQ ID NOs: 2652-2669; 1. nucleotide 12 through nucleotide 36 of any one of SEQ ID NOs: 2652-2669; m. nucleotide 13 through nucleotide 36 of any one of SEQ ID NOs: 2652-2669; n. nucleotide 14 through nucleotide 36 of any one of SEQ ID NOs: 2652-2669; or o. SEQ ID NO: 2670 or a portion thereof.

In another aspect of the RNA guide, the direct repeat comprises: a. nucleotide 1 through nucleotide 36 of a sequence that is at least 90% identical to SEQ ID NO: 2671; b. nucleotide 2 through nucleotide 36 of a sequence that is at least 90% identical to SEQ ID NO: 2671; c. nucleotide 3 through nucleotide 36 of a sequence that is at least 90% identical to SEQ ID NO: 2671; d. nucleotide 4 through nucleotide 36 of a sequence that is at least 90% identical to SEQ ID NO: 2671; e. nucleotide 5 through nucleotide 36 of a sequence that is at least 90% identical to SEQ ID NO: 2671; f. nucleotide 6 through nucleotide 36 of a sequence that is at least 90% identical to SEQ ID NO: 2671; g. nucleotide 7 through nucleotide 36 of a sequence that is at least 90% identical to SEQ ID NO: 2671; h. nucleotide 8 through nucleotide 36 of a sequence that is at least 90% identical to SEQ ID NO: 2671; i. nucleotide 9 through nucleotide 36 of a sequence that is at least 90% identical to SEQ ID NO: 2671; j. nucleotide 10 through nucleotide 36 of a sequence that is at least 90% identical to SEQ ID NO: 2671; k. nucleotide 11 through nucleotide 36 of a sequence that is at least 90% identical to SEQ ID NO: 2671; 1. nucleotide 12 through nucleotide 36 of a sequence that is at least 90% identical to SEQ ID NO: 2671; m. nucleotide 13 through nucleotide 36 of a sequence that is at least 90% identical to SEQ ID NO: 2671; n. nucleotide 14 through nucleotide 36 of a sequence that is at least 90% identical to SEQ ID NO: 2671; or o. a sequence that is at least 90% identical to a sequence of SEQ ID NO: 2672 or SEQ ID NO: 2673 or a portion thereof.

In another aspect of the RNA guide, the direct repeat comprises: a. nucleotide 1 through nucleotide 36 of SEQ ID NO: 2671; b. nucleotide 2 through nucleotide 36 of SEQ ID NO: 2671; c. nucleotide 3 through nucleotide 36 of SEQ ID NO: 2671; d. nucleotide 4 through nucleotide 36 of SEQ ID NO: 2671; e. nucleotide 5 through nucleotide 36 of SEQ ID NO: 2671; f. nucleotide 6 through nucleotide 36 of SEQ ID NO: 2671; g. nucleotide 7 through nucleotide 36 of SEQ ID NO: 2671; h. nucleotide 8 through nucleotide 36 of SEQ ID NO: 2671; i. nucleotide 9 through nucleotide 36 of SEQ ID NO: 2671; j. nucleotide 10 through nucleotide 36 of SEQ ID NO: 2671; k. nucleotide 11 through nucleotide 36 of SEQ ID NO: 2671; 1. nucleotide 12 through nucleotide 36 of SEQ ID NO: 2671; m. nucleotide 13 through nucleotide 36 of SEQ ID NO: 2671; n. nucleotide 14 through nucleotide 36 of SEQ ID NO: 2671; or o. SEQ ID NO: 2672 or SEQ ID NO: 2673 or a portion thereof.

In another aspect of the RNA guide, the direct repeat comprises: a. nucleotide 1 through nucleotide 36 of a sequence that is at least 90% identical to a sequence of SEQ ID NO: 2674 or SEQ ID NO: 2675; b. nucleotide 2 through nucleotide 36 of a sequence that is at least 90% identical to a sequence of SEQ ID NO: 2674 or SEQ ID NO: 2675; c. nucleotide 3 through nucleotide 36 of a sequence that is at least 90% identical to a sequence of SEQ ID NO: 2674 or SEQ ID NO: 2675; d. nucleotide 4 through nucleotide 36 of a sequence that is at least 90% identical to a sequence of SEQ ID NO: 2674 or SEQ ID NO: 2675; e. nucleotide 5 through nucleotide 36 of a sequence that is at least 90% identical to a sequence of SEQ ID NO: 2674 or SEQ ID NO: 2675; f. nucleotide 6 through nucleotide 36 of a sequence that is at least 90% identical to a sequence of SEQ ID NO: 2674 or SEQ ID NO: 2675; g. nucleotide 7 through nucleotide 36 of a sequence that is at least 90% identical to a sequence of SEQ ID NO: 2674 or SEQ ID NO: 2675; h. nucleotide 8 through nucleotide 36 of a sequence that is at least 90% identical to a sequence of SEQ ID NO: 2674 or SEQ ID NO: 2675; i. nucleotide 9 through nucleotide 36 of a sequence that is at least 90% identical to a sequence of SEQ ID NO: 2674 or SEQ ID NO: 2675; j. nucleotide 10 through nucleotide 36 of a sequence that is at least 90% identical to a sequence of SEQ ID NO: 2674 or SEQ ID NO: 2675; k. nucleotide 11 through nucleotide 36 of a sequence that is at least 90% identical to a sequence of SEQ ID NO: 2674 or SEQ ID NO: 2675; 1. nucleotide 12 through nucleotide 36 of a sequence that is at least 90% identical to a sequence of SEQ ID NO: 2674 or SEQ ID NO: 2675; m. nucleotide 13 through nucleotide 36 of a sequence that is at least 90% identical to a sequence of SEQ ID NO: 2674 or SEQ ID NO: 2675; n. nucleotide 14 through nucleotide 36 of a sequence that is at least 90% identical to a sequence of SEQ ID NO: 2674 or SEQ ID NO: 2675; o. nucleotide 15 through nucleotide 36 of a sequence that is at least 90% identical to a sequence of SEQ ID NO: 2674 or SEQ ID NO: 2675; or p. a sequence that is at least 90% identical to a sequence of SEQ ID NO: 2676 or a portion thereof.

In another aspect of the RNA guide, the direct repeat comprises: a. nucleotide 1 through nucleotide 36 of SEQ ID NO: 2674 or SEQ ID NO: 2675; b. nucleotide 2 through nucleotide 36 of SEQ ID NO: 2674 or SEQ ID NO: 2675; c. nucleotide 3 through nucleotide 36 of SEQ ID NO: 2674 or SEQ ID NO: 2675; d. nucleotide 4 through nucleotide 36 of SEQ ID NO: 2674 or SEQ ID NO: 2675; e. nucleotide 5 through nucleotide 36 of SEQ ID NO: 2674 or SEQ ID NO: 2675; f. nucleotide 6 through nucleotide 36 of SEQ ID NO: 2674 or SEQ ID NO: 2675; g. nucleotide 7 through nucleotide 36 of SEQ ID NO: 2674 or SEQ ID NO: 2675; h. nucleotide 8 through nucleotide 36 of SEQ ID NO: 2674 or SEQ ID NO: 2675; i. nucleotide 9 through nucleotide 36 of SEQ ID NO: 2674 or SEQ ID NO: 2675; j. nucleotide 10 through nucleotide 36 of SEQ ID NO: 2674 or SEQ ID NO: 2675; k. nucleotide 11 through nucleotide 36 of SEQ ID NO: 2674 or SEQ ID NO: 2675; 1. nucleotide 12 through nucleotide 36 of SEQ ID NO: 2674 or SEQ ID NO: 2675; m. nucleotide 13 through nucleotide 36 of SEQ ID NO: 2674 or SEQ ID NO: 2675; n. nucleotide 14 through nucleotide 36 of SEQ ID NO: 2674 or SEQ ID NO: 2675; o. nucleotide 15 through nucleotide 36 of SEQ ID NO: 2674 or SEQ ID NO: 2675; or p. SEQ ID NO: 2676 or a portion thereof.

In another aspect of the RNA guide, the spacer sequence is substantially complementary to the complement of a sequence of any one of SEQ ID NOs: 11-1321.

In another aspect of the RNA guide, the target sequence is adjacent to a protospacer adjacent motif (PAM) comprising the sequence 5′-NTTN-3′, wherein N is any nucleotide.

In another aspect of the RNA guide, the PAM comprises the sequence 5′-ATTA-3′, 5′-ATTT-3′, 5′-ATTG-3′, 5′-ATTC-3′, 5′-TTTA-3′, 5′-TTTT-3′, 5′-TTTG-3′, 5′-TTTC-3′, 5′-GTTA-3′, 5′-GTTT-3′, 5′-GTTG-3′, 5′-GTTC-3′, 5′-CTTA-3′, 5′-CTTT-3′, 5′-CTTG-3′, or 5′-CTTC-3′.

In another aspect of the RNA guide, the target sequence is immediately adjacent to the PAM sequence.

In another aspect of the RNA guide, the target sequence is within 1, 2, 3, 4, or 5 nucleotides of the PAM sequence.

The invention yet further provides a nucleic acid encoding an RNA guide as described herein.

The invention yet further provides a vector comprising such an RNA guide as described herein.

The invention yet further provides a cell comprising a composition, an RNA guide, a nucleic acid, or a vector as described herein.

In one aspect of the cell, the cell is a eukaryotic cell, an animal cell, a mammalian cell, a human cell, a primary cell, a cell line, a stem cell, or a T cell.

The invention yet further provides a kit comprising a composition, an RNA guide, a nucleic acid, or a vector as described herein.

The invention yet further provides a method of editing a BCL11A sequence, the method comprising contacting a BCL11A sequence with a composition or an RNA guide as described herein. In an embodiment, the method is carried out in vitro. In an embodiment, the method is carried out ex vivo.

In one aspect of the method, the BCL11A sequence is in a cell.

In one aspect of the method, the composition or the RNA guide induces a deletion in the BCL11A sequence.

In one aspect of the method, the deletion is adjacent to a 5′-NTTN-3′ sequence, wherein N is any nucleotide.

In one aspect of the method, the deletion is downstream of the 5′-NTTN-3′ sequence.

In one aspect of the method, the deletion is up to about 40 nucleotides in length.

In one aspect of the method, the deletion is from about 4 nucleotides to 40 nucleotides in length.

In one aspect of the method, the deletion is from about 4 nucleotides to 25 nucleotides in length.

In one aspect of the method, the deletion is from about 10 nucleotides to 25 nucleotides in length.

In one aspect of the method, the deletion is from about 10 nucleotides to 15 nucleotides in length.

In one aspect of the method, the deletion starts within about 5 nucleotides to about 15 nucleotides of the 5′-NTTN-3′ sequence.

In one aspect of the method, the deletion starts within about 5 nucleotides to about 10 nucleotides of the 5′-NTTN-3′ sequence.

In one aspect of the method, the deletion starts within about 10 nucleotides to about 15 nucleotides of the 5′-NTTN-3′ sequence.

In one aspect of the method, the deletion starts within about 5 nucleotides to about 15 nucleotides downstream of the 5′-NTTN-3′ sequence.

In one aspect of the method, the deletion starts within about 5 nucleotides to about 10 nucleotides downstream of the 5′-NTTN-3′ sequence.

In one aspect of the method, the deletion starts within about 10 nucleotides to about 15 nucleotides downstream of the 5′-NTTN-3′ sequence.

In one aspect of the method, the deletion ends within about 20 nucleotides to about 30 nucleotides of the 5′-NTTN-3′ sequence.

In one aspect of the method, the deletion ends within about 20 nucleotides to about 25 nucleotides of the 5′-NTTN-3′ sequence.

In one aspect of the method, the deletion ends within about 25 nucleotides to about 30 nucleotides of the 5′-NTTN-3′ sequence.

In one aspect of the method, the deletion ends within about 20 nucleotides to about 30 nucleotides downstream of the 5′-NTTN-3′ sequence.

In one aspect of the method, the deletion ends within about 20 nucleotides to about 25 nucleotides downstream of the 5′-NTTN-3′ sequence.

In one aspect of the method, the deletion ends within about 25 nucleotides to about 30 nucleotides downstream of the 5′-NTTN-3′ sequence.

In one aspect of the method, the deletion starts within about 5 nucleotides to about 15 nucleotides downstream of the 5′-NTTN-3′ sequence and ends within about 20 nucleotides to about 30 nucleotides downstream of the 5′-NTTN-3′ sequence.

In one aspect of the method, the deletion starts within about 5 nucleotides to about 15 nucleotides downstream of the 5′-NTTN-3′ sequence and ends within about 20 nucleotides to about 25 nucleotides downstream of the 5′-NTTN-3′ sequence.

In one aspect of the method, the deletion starts within about 5 nucleotides to about 15 nucleotides downstream of the 5′-NTTN-3′ sequence and ends within about 25 nucleotides to about 30 nucleotides downstream of the 5′-NTTN-3′ sequence.

In one aspect of the method, the deletion starts within about 5 nucleotides to about 10 nucleotides downstream of the 5′-NTTN-3′ sequence and ends within about 20 nucleotides to about 30 nucleotides downstream of the 5′-NTTN-3′ sequence.

In one aspect of the method, the deletion starts within about 5 nucleotides to about 10 nucleotides downstream of the 5′-NTTN-3′ sequence and ends within about 20 nucleotides to about 25 nucleotides downstream of the 5′-NTTN-3′ sequence.

In one aspect of the method, the deletion starts within about 5 nucleotides to about 10 nucleotides downstream of the 5′-NTTN-3′ sequence and ends within about 25 nucleotides to about 30 nucleotides downstream of the 5′-NTTN-3′ sequence.

In one aspect of the method, the deletion starts within about 10 nucleotides to about 15 nucleotides downstream of the 5′-NTTN-3′ sequence and ends within about 20 nucleotides to about 30 nucleotides downstream of the 5′-NTTN-3′ sequence.

In one aspect of the method, the deletion starts within about 10 nucleotides to about 15 nucleotides downstream of the 5′-NTTN-3′ sequence and ends within about 20 nucleotides to about 25 nucleotides downstream of the 5′-NTTN-3′ sequence.

In one aspect of the method, the deletion starts within about 10 nucleotides to about 15 nucleotides 5 downstream of the 5′-NTTN-3′ sequence and ends within about 25 nucleotides to about 30 nucleotides downstream of the 5′-NTTN-3′ sequence.

In one aspect of the method, the 5′-NTTN-3′ sequence is 5′-CTTT-3′, 5′-CTTC-3′, 5′-GTTT-3′, 5′-GTTC-3′, 5′-TTTC-3′, 5′-GTTA-3′, or 5′-GTTG-3′.

In one aspect of the method, the deletion overlaps with a mutation in the gene.

In one aspect of the method, the deletion overlaps with an insertion in the gene.

In one aspect of the method, the deletion removes a repeat expansion of the gene or a portion thereof.

In one aspect of the method, the deletion disrupts one or both alleles of the gene.

In one aspect of the method, the deletion disrupts a GATAA motif of an enhancer region of the BCL11A gene.

In one aspect of the composition, RNA guide, nucleic acid, vector, cell, kit or method described herein, the composition, RNA guide, nucleic acid, vector, cell, kit or method disrupts a GATAA motif of an enhancer region of the BCL11A gene.

In one aspect of the composition, cell, kit or method described herein, the composition, cell, kit or method comprises at least two RNA guides targeting a GATAA motif of an enhancer region of the BCL11A gene.

In one aspect of the composition, cell, kit or method described herein, the at least two RNA guides comprise at least 90% identity to:

(SEQ ID NO: 2677)

AGAAAUCCGUCUUUCAUUGACGGGAAGCUAGUCUAGUGCAAGC;

(SEQ ID NO: 2678)

AGAAAUCCGUCUUUCAUUGACGGCUGGAGCCUGUGAUAAAAGC;

and/or

(SEQ ID NO: 66)

AGAAAUCCGUCUUUCAUUGACGGUACCCCACCCACGCCCCCAC.

In one aspect of the composition, cell, kit or method described herein, the at least two RNA guides comprise at least 95% identity to:

(SEQ ID NO: 2677)

AGAAAUCCGUCUUUCAUUGACGGGAAGCUAGUCUAGUGCAAGC;

(SEQ ID NO: 2678)

AGAAAUCCGUCUUUCAUUGACGGCUGGAGCCUGUGAUAAAAGC;

and/or

(SEQ ID NO: 2679)

AGAAAUCCGUCUUUCAUUGACGGUACCCCACCCACGCCCCCAC.

In one aspect of the composition, cell, kit or method described herein, the at least two RNA guides comprise at least two sequences of:

(SEQ ID NO: 2677)

AGAAAUCCGUCUUUCAUUGACGGGAAGCUAGUCUAGUGCAAGC;

(SEQ ID NO: 2678)

AGAAAUCCGUCUUUCAUUGACGGCUGGAGCCUGUGAUAAAAGC;

and

(SEQ ID NO: 2679)

AGAAAUCCGUCUUUCAUUGACGGUACCCCACCCACGCCCCCAC.

In one aspect of the composition, RNA guide, nucleic acid, vector, cell, kit or method described herein, the RNA guide consists of the sequence of:

(SEQ ID NO: 2677)

AGAAAUCCGUCUUUCAUUGACGGGAAGCUAGUCUAGUGCAAGC;

(SEQ ID NO: 2678)

AGAAAUCCGUCUUUCAUUGACGGCUGGAGCCUGUGAUAAAAGC;

or

(SEQ ID NO: 2679)

AGAAAUCCGUCUUUCAUUGACGGUACCCCACCCACGCCCCCAC.

In one aspect of the composition, RNA guide, nucleic acid, vector, cell, kit or method described herein, the RNA guide does not consist of the sequence of:

(SEQ ID NO: 2677)

AGAAAUCCGUCUUUCAUUGACGGGAAGCUAGUCUAGUGCAAGC;

(SEQ ID NO: 2678)

AGAAAUCCGUCUUUCAUUGACGGCUGGAGCCUGUGAUAAAAGC;

or

(SEQ ID NO: 2679)

AGAAAUCCGUCUUUCAUUGACGGUACCCCACCCACGCCCCCAC.

Definitions

The present invention will be described with respect to particular embodiments, but the invention is not limited thereto but only by the claims. Terms as set forth hereinafter are generally to be understood in their common sense unless indicated otherwise.

As used herein, the term “activity” refers to a biological activity. In some embodiments, activity includes enzymatic activity, e.g., catalytic ability of an effector. For example, activity can include nuclease activity.

As used herein the term “BCL11A” refers to “B-cell lymphoma/leukemia 11A.” BCL11A plays a role in hematopoietic development and may also function as a leukemia disease gene. SEQ ID NO: 2635 as set forth herein provides an example of a BCL11A gene sequence. It is understood that spacer sequences described herein can target SEQ ID NO: 2635 or the reverse complement thereof, depending upon whether they are indicated as “+” or “−” as set forth in Table 5. The target sequences listed in Table 5 are on the non-target strand of the BCL11A gene.

As used herein, the term “Cas12i polypeptide” (also referred to herein as Cas12i) refers to a polypeptide that binds to a target sequence on a target nucleic acid specified by an RNA guide, wherein the polypeptide has at least some amino acid sequence homology to a wild-type Cas12i polypeptide. In some embodiments, the Cas12i polypeptide comprises at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity with any one of SEQ ID NOs: 1-5 and 11-18 of U.S. Pat. No. 10,808,245, which is incorporated by reference herein in its entirety. In some embodiments, a Cas12i polypeptide comprises at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity with any one of SEQ ID NO: 3 (Cas12i1), SEQ ID NO: 5 (Cas12i2), SEQ ID NO: 14 (Cas12i3), or SEQ ID NO: 16 (Cas12i4) of U.S. Pat. No. 10,808,245, corresponding to SEQ ID NOs: 2650, 2634, 2651, and 2647 of the present application. In some embodiments, a Cas12i polypeptide of the disclosure is a Cas12i1 polypeptide or Cas12i2 polypeptide as described in PCT/US2021/025257. In some embodiments, the Cas12i polypeptide cleaves a target nucleic acid (e.g., as a nick or a double strand break).

As used herein, the term “complex” refers to a grouping of two or more molecules. In some embodiments, the complex comprises a polypeptide and a nucleic acid molecule interacting with (e.g., binding to, coming into contact with, adhering to) one another. As used herein, the term “complex” can refer to a grouping of an RNA guide and a polypeptide (e.g., a Cas12i polypeptide). As used herein, the term “complex” can refer to a grouping of an RNA guide, a polypeptide, and a target sequence. As used herein, the term “complex” can refer to a grouping of a BCL11A-targeting RNA guide and a Cas12i polypeptide.

As used herein, the term “protospacer adjacent motif” or “PAM” refers to a DNA sequence adjacent to a target sequence (e.g., a BCL11A target sequence) to which a complex comprising an RNA guide (e.g., a BCL11A-targeting RNA guide) and a Cas12i polypeptide binds. In the case of a double-stranded target, the RNA guide binds to a first strand of the target (e.g., the target strand or the spacer-complementary strand), and a PAM sequence as described herein is present in the second, complementary strand (e.g., the non-target strand or the non-spacer-complementary strand). As used herein, the term “adjacent” includes instances in which the RNA guide of a complex comprising an RNA guide and a Cas12i polypeptide specifically binds, interacts, or associates with a target sequence that is immediately adjacent to a PAM. In such instances, there are no nucleotides between the target sequence and the PAM. The term “adjacent” also includes instances in which there are a small number (e.g., 1, 2, 3, 4, or 5) of nucleotides between the target sequence, to which the RNA guide binds, and the PAM. In some embodiments, the PAM sequence as described herein is present in the non-target strand (e.g., the non-spacer-complementary strand). In such a case, the term “adjacent” includes a PAM sequence as described herein as being immediately adjacent to (or within a small number, e.g., 1, 2, 3, 4, or 5 nucleotides of) a sequence in the non-target strand.

As used herein, the term “RNA guide” refers to any RNA molecule that facilitates the targeting of a polypeptide (e.g., a Cas12i polypeptide) described herein to a target sequence (e.g., a sequence of a BCL11A gene). An RNA guide may be designed to include sequences that are complementary to a specific nucleic acid sequence (e.g., a BCL11A nucleic acid sequence). An RNA guide may comprise a DNA targeting sequence (i.e., a spacer sequence) and a direct repeat (DR) sequence. The term “crRNA” is also used herein to refer to an RNA guide.

In some embodiments, a spacer sequence is complementary to a target sequence. As used herein, the term “complementary” refers to the ability of nucleobases of a first nucleic acid molecule, such as an RNA guide, to base pair with nucleobases of a second nucleic acid molecule, such as a target sequence. Two complementary nucleic acid molecules are able to non-covalently bind under appropriate temperature and solution ionic strength conditions. In some embodiments, a first nucleic acid molecule (e.g., a spacer sequence of an RNA guide) comprises 100% complementarity to a second nucleic acid (e.g., a target sequence). In some embodiments, a first nucleic acid molecule (e.g., a spacer sequence of an RNA guide) is complementary to a second nucleic acid molecule (e.g., a target sequence) if the first nucleic acid molecule comprises at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% complementarity to the second nucleic acid. As used herein, the term “substantially complementary” refers to a polynucleotide (e.g., a spacer sequence of an RNA guide) that has a certain level of complementarity to a target sequence. In some embodiments, the level of complementarity is such that the polynucleotide can hybridize to the target sequence with sufficient affinity to permit an effector polypeptide (e.g., Cas12i) that is complexed with the polynucleotide to act (e.g., cleave) on the target sequence. In some embodiments, a spacer sequence that is substantially complementary to a target sequence has less than 100% complementarity to the target sequence. In some embodiments, a spacer sequence that is substantially complementary to a target sequence has at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% complementarity to the target sequence. In some embodiments, an RNA guide with a spacer sequence that is substantially complementary to a target sequence has 100% complementarity to the target sequence.

As used herein, the terms “target” and “target sequence” refer to a nucleic acid sequence to which an RNA guide specifically binds. In some embodiments, the DNA targeting sequence (e.g., spacer) of an RNA guide binds to a target sequence. In the case of a double-stranded target, the RNA guide binds to a first strand of the target (i.e., the target strand or the spacer-complementary strand), and a PAM sequence as described herein is present in the second, complementary strand (i.e., the non-target strand or the non-spacer-complementary strand). In some embodiments, the target strand (i.e., the spacer-complementary strand) comprises a 5′-NAAN-3′ sequence. In some embodiments, the target sequence is a sequence within a BCL11A gene sequence, including, but not limited, to the sequence set forth in SEQ ID NO: 2635 or the reverse complement thereof.

As used herein, the terms “upstream” and “downstream” refer to relative positions within a single nucleic acid (e.g., DNA) sequence in a nucleic acid molecule. “Upstream” and “downstream” relate to the 5′ to 3′ direction, respectively, in which RNA transcription occurs. A first sequence is upstream of a second sequence when the 3′ end of the first sequence occurs before the 5′ end of the second sequence. A first sequence is downstream of a second sequence when the 5′ end of the first sequence occurs after the 3′ end of the second sequence. In some embodiments, the 5′-NTTN-3′ sequence is upstream of an indel described herein, and a Cas12i-induced indel is downstream of the 5′-NTTN-3′ sequence.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows indel activity in CD34+ HSPC cells after targeting BCL11A intronic erythroid enhancer with different individual and multiplexed crRNAs in complex with a variant Cas12i2 of SEQ ID NO: 2642 at various RNP concentrations. Error bars represent standard deviation of the mean of two bioreplicates (two individual donors).

FIG. 2 shows viability of modified CD34+ HSPC cells 72 hours following targeting of BCL11A intronic erythroid enhancer in primary CD34+ HSPCs. Different concentrations of BCL11A intronic erythroid enhancer targeting RNPs comprising variant Cas12i2 of SEQ ID NO: 2642 and crRNAs were tested. crRNAs were tested individually and in multiplexed configuration. Error bars represent standard deviation of the mean of two bioreplicates (two individual donors).

DETAILED DESCRIPTION

The present disclosure relates to an RNA guide capable of binding to BCL11A and methods of use thereof. In some aspects, a composition comprising an RNA guide having one or more characteristics is described herein. In some aspects, a method of producing the RNA guide is described. In some aspects, a method of delivering a composition comprising the RNA guide is described.

Composition

In some aspects, the invention described herein comprises compositions comprising an RNA guide targeting a BCL11A gene or a portion of the BCL11A gene. In some embodiments, the RNA guide is comprised of a direct repeat component and a spacer component. In some embodiments, the RNA guide binds a Cas12i polypeptide. In some embodiments, the spacer component is substantially complementary to a BCL11A target sequence, wherein the BCL11A target sequence is adjacent to a 5′-NTTN-3′ PAM sequence as described herein. In the case of a double-stranded target, the RNA guide binds to a first strand of the target (i.e., the target strand or the spacer-complementary strand) and a PAM sequence as described herein is present in the second, complementary strand (i.e., the non-target strand or the non-spacer-complementary strand).

In some embodiments, the invention described herein comprises compositions comprising a complex, wherein the complex comprises an RNA guide targeting BCL11A. In some embodiments, the invention comprises a complex comprising an RNA guide and a Cas12i polypeptide. In some embodiments, the RNA guide and the Cas12i polypeptide bind to each other in a molar ratio of about 1:1. In some embodiments, a complex comprising an RNA guide and a Cas12i polypeptide binds to a BCL11A target sequence. In some embodiments, a complex comprising an RNA guide targeting BCL11A and a Cas12i polypeptide binds to a BCL11A target sequence at a molar ratio of about 1:1. In some embodiments, the complex comprises enzymatic activity, such as nuclease activity, that can cleave the BCL11A target sequence. The RNA guide, the Cas12i polypeptide, and the BCL11A target sequence, either alone or together, do not naturally occur.

Use of the compositions disclosed herein has advantages over those of other known nuclease systems. Cas12i polypeptides are smaller than other nucleases. For example, Cas12i2 is 1,054 amino acids in length, whereas S. pyogenes Cas9 (SpCas9) is 1,368 amino acids in length, S. thermophilus Cas9 (StCas9) is 1,128 amino acids in length, FnCpf1 is 1,300 amino acids in length, AsCpf1 is 1,307 amino acids in length, and LbCpf1 is 1,246 amino acids in length. Cas12i RNA guides, which do not require a trans-activating CRISPR RNA (tracrRNA), are also smaller than Cas9 RNA guides. The smaller Cas12i polypeptide and RNA guide sizes are beneficial for delivery. Compositions comprising a Cas12i polypeptide also demonstrate decreased off-target activity compared to compositions comprising an SpCas9 polypeptide. See PCT/US2021/025257, which is incorporated by reference in its entirety. Furthermore, indels induced by compositions comprising a Cas12i polypeptide differ from indels induced by compositions comprising an SpCas9 polypeptide. For example, SpCas9 polypeptides primarily induce insertions and deletions of 1 nucleotide in length. However, Cas12i polypeptides induce larger deletions, which can be beneficial in disrupting a larger portion of a gene such as BCL11A.

RNA Guide

In some embodiments, the composition described herein comprises an RNA guide targeting BCL11A. In some embodiments, the composition described herein comprises two or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or more) RNA guides targeting BCL11A.

The RNA guide may direct the Cas12i polypeptide as described herein to a BCL11A target sequence. Two or more RNA guides may target two or more separate Cas12i polypeptides (e.g., Cas12i polypeptides having the same or different sequence) as described herein to two or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or more) BCL11A target sequences.

Those skilled in the art reading the below examples of particular kinds of RNA guides will understand that, in some embodiments, an RNA guide is BCL11A target-specific. That is, in some embodiments, an RNA guide binds specifically to one or more BCL11A target sequences (e.g., within a cell) and not to non-targeted sequences (e.g., non-specific DNA or random sequences within the same cell).

In some embodiments, the RNA guide comprises a spacer sequence followed by a direct repeat sequence, referring to the sequences in the 5′ to 3′ direction. In some embodiments, the RNA guide comprises a first direct repeat sequence followed by a spacer sequence and a second direct repeat sequence, referring to the sequences in the 5′ to 3′ direction. In some embodiments, the first and second direct repeats of such an RNA guide are identical. In some embodiments, the first and second direct repeats of such an RNA guide are different.

In some embodiments, the spacer sequence and the direct repeat sequence(s) of the RNA guide are present within the same RNA molecule. In some embodiments, the spacer and direct repeat sequences are linked directly to one another. In some embodiments, a short linker is present between the spacer and direct repeat sequences, e.g., an RNA linker of 1, 2, or 3 nucleotides in length. In some embodiments, the spacer sequence and the direct repeat sequence(s) of the RNA guide are present in separate molecules, which are joined to one another by base pairing interactions.

Additional information regarding exemplary direct repeat and spacer components of RNA guides is provided as follows.

Direct Repeat

In some embodiments, the RNA guide comprises a direct repeat sequence. In some embodiments, the direct repeat sequence of the RNA guide has a length of between 12-100, 13-75, 14-50, or 15-40 nucleotides (e.g., 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, or 40 nucleotides).

In some embodiments, the direct repeat sequence is or comprises a sequence of Table 1 or a portion of a sequence of Table 1. The direct repeat sequence can comprise nucleotide 1 through nucleotide 36 of any one of SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, or 8. The direct repeat sequence can comprise nucleotide 2 through nucleotide 36 of any one of SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, or 8. The direct repeat sequence can comprise nucleotide 3 through nucleotide 36 of any one of SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, or 8. The direct repeat sequence can comprise nucleotide 4 through nucleotide 36 of any one of SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, or 8. The direct repeat sequence can comprise nucleotide 5 through nucleotide 36 of any one of SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, or 8. The direct repeat sequence can comprise nucleotide 6 through nucleotide 36 of any one of SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, or 8. The direct repeat sequence can comprise nucleotide 7 through nucleotide 36 of any one of SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, or 8. The direct repeat sequence can comprise nucleotide 8 through nucleotide 36 of any one of SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, or 8. The direct repeat sequence can comprise nucleotide 9 through nucleotide 36 of any one of SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, or 8. The direct repeat sequence can comprise nucleotide 10 through nucleotide 36 of any one of SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, or 8. The direct repeat sequence can comprise nucleotide 11 through nucleotide 36 of any one of SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, or 8. The direct repeat sequence can comprise nucleotide 12 through nucleotide 36 of any one of SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, or 8. The direct repeat sequence can comprise nucleotide 13 through nucleotide 36 of any one of SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, or 8. The direct repeat sequence can comprise nucleotide 14 through nucleotide 36 of any one of SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, or 8. The direct repeat sequence can comprise nucleotide 1 through nucleotide 34 of SEQ ID NO: 9. The direct repeat sequence can comprise nucleotide 2 through nucleotide 34 of SEQ ID NO: 9. The direct repeat sequence can comprise nucleotide 3 through nucleotide 34 of SEQ ID NO: 9. The direct repeat sequence can comprise nucleotide 4 through nucleotide 34 of SEQ ID NO: 9. The direct repeat sequence can comprise nucleotide 5 through nucleotide 34 of SEQ ID NO: 9. The direct repeat sequence can comprise nucleotide 6 through nucleotide 34 of SEQ ID NO: 9. The direct repeat sequence can comprise nucleotide 7 through nucleotide 34 of SEQ ID NO: 9. The direct repeat sequence can comprise nucleotide 8 through nucleotide 34 of SEQ ID NO: 9. The direct repeat sequence can comprise nucleotide 9 through nucleotide 34 of SEQ ID NO: 9. The direct repeat sequence can comprise nucleotide 10 through nucleotide 34 of SEQ ID NO: 9. The direct repeat sequence can comprise nucleotide 11 through nucleotide 34 of SEQ ID NO: 9. The direct repeat sequence can comprise nucleotide 12 through nucleotide 34 of SEQ ID NO: 9. In some embodiments, the direct repeat sequence is set forth in SEQ ID NO: 10. In some embodiments, the direct repeat sequence comprises a portion of the sequence set forth in SEQ ID NO: 10.

In some embodiments, the direct repeat sequence has or comprises a sequence comprising at least 90% identity (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity) to a sequence of Table 1 or a portion of a sequence of Table 1. The direct repeat sequence can have or comprise a sequence having at least 90% identity to a sequence comprising nucleotide 1 through nucleotide 36 of any one of SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, or 8. The direct repeat sequence can have or comprise a sequence having at least 90% identity to a sequence comprising 2 through nucleotide 36 of any one of SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, or 8. The direct repeat sequence can have or comprise a sequence having at least 90% identity to a sequence comprising 3 through nucleotide 36 of any one of SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, or 8. The direct repeat sequence can have or comprise a sequence having at least 90% identity to a sequence comprising 4 through nucleotide 36 of any one of SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, or 8. The direct repeat sequence can have or comprise a sequence having at least 90% identity to a sequence comprising 5 through nucleotide 36 of any one of SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, or 8. The direct repeat sequence can have or comprise a sequence having at least 90% identity to a sequence comprising 6 through nucleotide 36 of any one of SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, or 8. The direct repeat sequence can have or comprise a sequence having at least 90% identity to a sequence comprising 7 through nucleotide 36 of any one of SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, or 8. The direct repeat sequence can have or comprise a sequence having at least 90% identity to a sequence comprising 8 through nucleotide 36 of any one of SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, or 8. The direct repeat sequence can have or comprise a sequence having at least 90% identity to a sequence comprising 9 through nucleotide 36 of any one of SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, or 8. The direct repeat sequence can have or comprise a sequence having at least 90% identity to a sequence comprising 10 through nucleotide 36 of any one of SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, or 8. The direct repeat sequence can have or comprise a sequence having at least 90% identity to a sequence comprising 11 through nucleotide 36 of any one of SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, or 8. The direct repeat sequence can have or comprise a sequence having at least 90% identity to a sequence comprising 12 through nucleotide 36 of any one of SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, or 8. The direct repeat sequence can have or comprise a sequence having at least 90% identity to a sequence comprising 13 through nucleotide 36 of any one of SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, or 8. The direct repeat sequence can have or comprise a sequence having at least 90% identity to a sequence comprising 14 through nucleotide 36 of any one of SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, or 8. The direct repeat sequence can have or comprise a sequence having at least 90% identity to a sequence comprising 1 through nucleotide 34 of SEQ ID NO: 9. The direct repeat sequence can have or comprise a sequence having at least 90% identity to a sequence comprising 2 through nucleotide 34 of SEQ ID NO: 9. The direct repeat sequence can have or comprise a sequence having at least 90% identity to a sequence comprising 3 through nucleotide 34 of SEQ ID NO: 9. The direct repeat sequence can have or comprise a sequence having at least 90% identity to a sequence comprising 4 through nucleotide 34 of SEQ ID NO: 9. The direct repeat sequence can have or comprise a sequence having at least 90% identity to a sequence comprising 5 through nucleotide 34 of SEQ ID NO: 9. The direct repeat sequence can have or comprise a sequence having at least 90% identity to a sequence comprising 6 through nucleotide 34 of SEQ ID NO: 9. The direct repeat sequence can have or comprise a sequence having at least 90% identity to a sequence comprising 7 through nucleotide 34 of SEQ ID NO: 9. The direct repeat sequence can have or comprise a sequence having at least 90% identity to a sequence comprising 8 through nucleotide 34 of SEQ ID NO: 9. The direct repeat sequence can have or comprise a sequence having at least 90% identity to a sequence comprising 9 through nucleotide 34 of SEQ ID NO: 9. The direct repeat sequence can have or comprise a sequence having at least 90% identity to a sequence comprising 10 through nucleotide 34 of SEQ ID NO: 9. The direct repeat sequence can have or comprise a sequence having at least 90% identity to a sequence comprising 11 through nucleotide 34 of SEQ ID NO: 9. The direct repeat sequence can have or comprise a sequence having at least 90% identity to a sequence comprising 12 through nucleotide 34 of SEQ ID NO: 9. In some embodiments, the direct repeat sequence has at least 90% identity (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity) to SEQ ID NO: 10. In some embodiments, the direct repeat sequence has at least 90% identity to a portion of the sequence set forth in SEQ ID NO: 10.

In some embodiments, compositions comprising a Cas12i2 polypeptide and an RNA guide comprising the direct repeat of SEQ ID NO: 10 and a spacer length of 20 nucleotides are capable of introducing indels into a BCL11A target sequence. See Example 1.

In some embodiments, the direct repeat sequence is or comprises a sequence that is at least 90% identical to the reverse complement of any one of SEQ ID NOs: 1-10. In some embodiments, the direct repeat sequence is or comprises the reverse complement of any one of SEQ ID NOs: 1-10.

TABLE 1

Direct repeat sequences

Sequence

identifier
Direct Repeat Sequence

SEQ ID NO: 1
GUUGCAAAACCCAAGAAA

UCCGUCUUUCAUUGACGG

SEQ ID NO: 2
AAUAGCGGCCCUAAGAAA

UCCGUCUUUCAUUGACGG

SEQ ID NO: 3
AUUGGAACUGGCGAGAAA

UCCGUCUUUCAUUGACGG

SEQ ID NO: 4
CCAGCAACACCUAAGAAA

UCCGUCUUUCAUUGACGG

SEQ ID NO: 5
CGGCGCUCGAAUAGGAAA

UCCGUCUUUCAUUGACGG

SEQ ID NO: 6
GUGGCAACACCUAAGAAA

UCCGUCUUUCAUUGACGG

SEQ ID NO: 7
GUUGCAACACCUAAGAAA

UCCGUCUUUCAUUGACGG

SEQ ID NO: 8
GUUGCAAUGCCUAAGAAA

UCCGUCUUUCAUUGACGG

SEQ ID NO: 9
GCAACACCUAAGAAAUCC

GUCUUUCAUUGACGGG

SEQ ID NO: 10
AGAAAUCCGUCUUUCAUU

GACGG

In some embodiments, the direct repeat sequence is a sequence of Table 2 or a portion of a sequence of Table 2. The direct repeat sequence can comprise nucleotide 1 through nucleotide 36 of any one of SEQ ID NOs: 2652, 2653, 2654, 2655, 2656, 2657, 2658, 2659, 2660, 2661, 2662, 2663, 2664, 2665, 2666, 2667, 2668, or 2669. The direct repeat sequence can comprise nucleotide 2 through nucleotide 36 of any one of SEQ ID NOs: 2652, 2653, 2654, 2655, 2656, 2657, 2658, 2659, 2660, 2661, 2662, 2663, 2664, 2665, 2666, 2667, 2668, or 2669. The direct repeat sequence can comprise nucleotide 3 through nucleotide 36 of any one of SEQ ID NOs: 2652, 2653, 2654, 2655, 2656, 2657, 2658, 2659, 2660, 2661, 2662, 2663, 2664, 2665, 2666, 2667, 2668, or 2669. The direct repeat sequence can comprise nucleotide 4 through nucleotide 36 of any one of SEQ ID NOs: 2652, 2653, 2654, 2655, 2656, 2657, 2658, 2659, 2660, 2661, 2662, 2663, 2664, 2665, 2666, 2667, 2668, or 2669. The direct repeat sequence can comprise nucleotide 5 through nucleotide 36 of any one of SEQ ID NOs: 2652, 2653, 2654, 2655, 2656, 2657, 2658, 2659, 2660, 2661, 2662, 2663, 2664, 2665, 2666, 2667, 2668, or 2669. The direct repeat sequence can comprise nucleotide 6 through nucleotide 36 of any one of SEQ ID NOs: 2652, 2653, 2654, 2655, 2656, 2657, 2658, 2659, 2660, 2661, 2662, 2663, 2664, 2665, 2666, 2667, 2668, or 2669. The direct repeat sequence can comprise nucleotide 7 through nucleotide 36 of any one of SEQ ID NOs: 2652, 2653, 2654, 2655, 2656, 2657, 2658, 2659, 2660, 2661, 2662, 2663, 2664, 2665, 2666, 2667, 2668, or 2669. The direct repeat sequence can comprise nucleotide 8 through nucleotide 36 of any one of SEQ ID NOs: 2652, 2653, 2654, 2655, 2656, 2657, 2658, 2659, 2660, 2661, 2662, 2663, 2664, 2665, 2666, 2667, 2668, or 2669. The direct repeat sequence can comprise nucleotide 9 through nucleotide 36 of any one of SEQ ID NOs: 2652, 2653, 2654, 2655, 2656, 2657, 2658, 2659, 2660, 2661, 2662, 2663, 2664, 2665, 2666, 2667, 2668, or 2669. The direct repeat sequence can comprise nucleotide 10 through nucleotide 36 of any one of SEQ ID NOs: 2652, 2653, 2654, 2655, 2656, 2657, 2658, 2659, 2660, 2661, 2662, 2663, 2664, 2665, 2666, 2667, 2668, or 2669. The direct repeat sequence can comprise nucleotide 11 through nucleotide 36 of any one of SEQ ID NOs: 2652, 2653, 2654, 2655, 2656, 2657, 2658, 2659, 2660, 2661, 2662, 2663, 2664, 2665, 2666, 2667, 2668, or 2669. The direct repeat sequence can comprise nucleotide 12 through nucleotide 36 of any one of SEQ ID NOs: 2652, 2653, 2654, 2655, 2656, 2657, 2658, 2659, 2660, 2661, 2662, 2663, 2664, 2665, 2666, 2667, 2668, or 2669. The direct repeat sequence can comprise nucleotide 13 through nucleotide 36 of any one of SEQ ID NOs: 2652, 2653, 2654, 2655, 2656, 2657, 2658, 2659, 2660, 2661, 2662, 2663, 2664, 2665, 2666, 2667, 2668, or 2669. The direct repeat sequence can comprise nucleotide 14 through nucleotide 36 of any one of SEQ ID NOs: 2652, 2653, 2654, 2655, 2656, 2657, 2658, 2659, 2660, 2661, 2662, 2663, 2664, 2665, 2666, 2667, 2668, or 2669.

In some embodiments, the direct repeat sequence has at least 95% identity (e.g., at least 95%, 96%, 97%, 98% or 99% identity) to a sequence of Table 2 or a portion of a sequence of Table 2. The direct repeat sequence can have at least 95% identity to a sequence comprising nucleotide 1 through nucleotide 36 of any one of SEQ ID NOs: 2652, 2653, 2654, 2655, 2656, 2657, 2658, 2659, 2660, 2661, 2662, 2663, 2664, 2665, 2666, 2667, 2668, or 2669. The direct repeat sequence can have at least 95% identity to a sequence comprising 2 through nucleotide 36 of any one of SEQ ID NOs: 2652, 2653, 2654, 2655, 2656, 2657, 2658, 2659, 2660, 2661, 2662, 2663, 2664, 2665, 2666, 2667, 2668, or 2669. The direct repeat sequence can have at least 95% identity to a sequence comprising 3 through nucleotide 36 of any one of SEQ ID NOs: 2652, 2653, 2654, 2655, 2656, 2657, 2658, 2659, 2660, 2661, 2662, 2663, 2664, 2665, 2666, 2667, 2668, or 2669. The direct repeat sequence can have at least 95% identity to a sequence comprising 4 through nucleotide 36 of any one of SEQ ID NOs: 2652, 2653, 2654, 2655, 2656, 2657, 2658, 2659, 2660, 2661, 2662, 2663, 2664, 2665, 2666, 2667, 2668, or 2669. The direct repeat sequence can have at least 95% identity to a sequence comprising 5 through nucleotide 36 of any one of SEQ ID NOs: 2652, 2653, 2654, 2655, 2656, 2657, 2658, 2659, 2660, 2661, 2662, 2663, 2664, 2665, 2666, 2667, 2668, or 2669. The direct repeat sequence can have at least 95% identity to a sequence comprising 6 through nucleotide 36 of any one of SEQ ID NOs: 2652, 2653, 2654, 2655, 2656, 2657, 2658, 2659, 2660, 2661, 2662, 2663, 2664, 2665, 2666, 2667, 2668, or 2669. The direct repeat sequence can have at least 95% identity to a sequence comprising 7 through nucleotide 36 of any one of SEQ ID NOs: 2652, 2653, 2654, 2655, 2656, 2657, 2658, 2659, 2660, 2661, 2662, 2663, 2664, 2665, 2666, 2667, 2668, or 2669. The direct repeat sequence can have at least 95% identity to a sequence comprising 8 through nucleotide 36 of any one of SEQ ID NOs: 2652, 2653, 2654, 2655, 2656, 2657, 2658, 2659, 2660, 2661, 2662, 2663, 2664, 2665, 2666, 2667, 2668, or 2669. The direct repeat sequence can have at least 95% identity to a sequence comprising 9 through nucleotide 36 of any one of SEQ ID NOs: 2652, 2653, 2654, 2655, 2656, 2657, 2658, 2659, 2660, 2661, 2662, 2663, 2664, 2665, 2666, 2667, 2668, or 2669. The direct repeat sequence can have at least 95% identity to a sequence comprising 10 through nucleotide 36 of any one of SEQ ID NOs: 2652, 2653, 2654, 2655, 2656, 2657, 2658, 2659, 2660, 2661, 2662, 2663, 2664, 2665, 2666, 2667, 2668, or 2669. The direct repeat sequence can have at least 95% identity to a sequence comprising 11 through nucleotide 36 of any one of SEQ ID NOs: 2652, 2653, 2654, 2655, 2656, 2657, 2658, 2659, 2660, 2661, 2662, 2663, 2664, 2665, 2666, 2667, 2668, or 2669. The direct repeat sequence can have at least 95% identity to a sequence comprising 12 through nucleotide 36 of any one of SEQ ID NOs: 2652, 2653, 2654, 2655, 2656, 2657, 2658, 2659, 2660, 2661, 2662, 2663, 2664, 2665, 2666, 2667, 2668, or 2669. The direct repeat sequence can have at least 95% identity to a sequence comprising 13 through nucleotide 36 of any one of SEQ ID NOs: 2652, 2653, 2654, 2655, 2656, 2657, 2658, 2659, 2660, 2661, 2662, 2663, 2664, 2665, 2666, 2667, 2668, or 2669.

In some embodiments, the direct repeat sequence has at least 90% identity (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity) to a sequence of Table 2 or a portion of a sequence of Table 2. The direct repeat sequence can have at least 90% identity to a sequence comprising nucleotide 1 through nucleotide 36 of any one of SEQ ID NOs: 2652, 2653, 2654, 2655, 2656, 2657, 2658, 2659, 2660, 2661, 2662, 2663, 2664, 2665, 2666, 2667, 2668, or 2669. The direct repeat sequence can have at least 90% identity to a sequence comprising 2 through nucleotide 36 of any one of SEQ ID NOs: 2652, 2653, 2654, 2655, 2656, 2657, 2658, 2659, 2660, 2661, 2662, 2663, 2664, 2665, 2666, 2667, 2668, or 2669. The direct repeat sequence can have at least 90% identity to a sequence comprising 3 through nucleotide 36 of any one of SEQ ID NOs: 2652, 2653, 2654, 2655, 2656, 2657, 2658, 2659, 2660, 2661, 2662, 2663, 2664, 2665, 2666, 2667, 2668, or 2669. The direct repeat sequence can have at least 90% identity to a sequence comprising 4 through nucleotide 36 of any one of SEQ ID NOs: 2652, 2653, 2654, 2655, 2656, 2657, 2658, 2659, 2660, 2661, 2662, 2663, 2664, 2665, 2666, 2667, 2668, or 2669. The direct repeat sequence can have at least 90% identity to a sequence comprising 5 through nucleotide 36 of any one of SEQ ID NOs: 2652, 2653, 2654, 2655, 2656, 2657, 2658, 2659, 2660, 2661, 2662, 2663, 2664, 2665, 2666, 2667, 2668, or 2669. The direct repeat sequence can have at least 90% identity to a sequence comprising 6 through nucleotide 36 of any one of SEQ ID NOs: 2652, 2653, 2654, 2655, 2656, 2657, 2658, 2659, 2660, 2661, 2662, 2663, 2664, 2665, 2666, 2667, 2668, or 2669. The direct repeat sequence can have at least 90% identity to a sequence comprising 7 through nucleotide 36 of any one of SEQ ID NOs: 2652, 2653, 2654, 2655, 2656, 2657, 2658, 2659, 2660, 2661, 2662, 2663, 2664, 2665, 2666, 2667, 2668, or 2669. The direct repeat sequence can have at least 90% identity to a sequence comprising 8 through nucleotide 36 of any one of SEQ ID NOs: 2652, 2653, 2654, 2655, 2656, 2657, 2658, 2659, 2660, 2661, 2662, 2663, 2664, 2665, 2666, 2667, 2668, or 2669. The direct repeat sequence can have at least 90% identity to a sequence comprising 9 through nucleotide 36 of any one of SEQ ID NOs: 2652, 2653, 2654, 2655, 2656, 2657, 2658, 2659, 2660, 2661, 2662, 2663, 2664, 2665, 2666, 2667, 2668, or 2669. The direct repeat sequence can have at least 90% identity to a sequence comprising 10 through nucleotide 36 of any one of SEQ ID NOs: 2652, 2653, 2654, 2655, 2656, 2657, 2658, 2659, 2660, 2661, 2662, 2663, 2664, 2665, 2666, 2667, 2668, or 2669. The direct repeat sequence can have at least 90% identity to a sequence comprising 11 through nucleotide 36 of any one of SEQ ID NOs: 2652, 2653, 2654, 2655, 2656, 2657, 2658, 2659, 2660, 2661, 2662, 2663, 2664, 2665, 2666, 2667, 2668, or 2669. The direct repeat sequence can have at least 90% identity to a sequence comprising 12 through nucleotide 36 of any one of SEQ ID NOs: 2652, 2653, 2654, 2655, 2656, 2657, 2658, 2659, 2660, 2661, 2662, 2663, 2664, 2665, 2666, 2667, 2668, or 2669. The direct repeat sequence can have at least 90% identity to a sequence comprising 13 through nucleotide 36 of any one of SEQ ID NOs: 2652, 2653, 2654, 2655, 2656, 2657, 2658, 2659, 2660, 2661, 2662, 2663, 2664, 2665, 2666, 2667, 2668, or 2669.

In some embodiments, the direct repeat sequence is at least 90% identical to the reverse complement of any one of SEQ ID NOs: 2652, 2653, 2654, 2655, 2656, 2657, 2658, 2659, 2660, 2661, 2662, 2663, 2664, 2665, 2666, 2667, 2668, or 2669. In some embodiments, the direct repeat sequence is at least 95% identical to the reverse complement of any one of SEQ ID NOs: 2652, 2653, 2654, 2655, 2656, 2657, 2658, 2659, 2660, 2661, 2662, 2663, 2664, 2665, 2666, 2667, 2668, or 2669. In some embodiments, the direct repeat sequence is the reverse complement of any one of SEQ ID NOs: 2652, 2653, 2654, 2655, 2656, 2657, 2658, 2659, 2660, 2661, 2662, 2663, 2664, 2665, 2666, 2667, 2668, or 2669.

In some embodiments, the direct repeat sequence is at least 90% identical to SEQ ID NO: 2670 or a portion of SEQ ID NO: 2670. In some embodiments, the direct repeat sequence is at least 95% identical to SEQ ID NO: 2670 or a portion of SEQ ID NO: 2670. In some embodiments, the direct repeat sequence is 100% identical to SEQ ID NO: 2670 or a portion of SEQ ID NO: 2670.

TABLE 2

Cas1214 direct repeat sequences.

Sequence identifier
Direct Repeat Sequence

SEQ ID NO: 2652
UCUCAACGAUAGUCAGAC

AUGUGUCCUCAGUGACAC

SEQ ID NO: 2653
UUUUAACAACACUCAGGC

AUGUGUCCACAGUGACAC

SEQ ID NO: 2654
UUGAACGGAUACUCAGAC

AUGUGUUUCCAGUGACAC

SEQ ID NO: 2655
UGCCCUCAAUAGUCAGAU

GUGUGUCCACAGUGACAC

SEQ ID NO: 2656
UCUCAAUGAUACUUAGAU

ACGUGUCCUCAGUGACAC

SEQ ID NO: 2657
UCUCAAUGAUACUCAGAC

AUGUGUCCCCAGUGACAC

SEQ ID NO: 2658
UCUCAAUGAUACUAAGAC

AUGUGUCCUCAGUGACAC

SEQ ID NO: 2659
UCUCAACUAUACUCAGAC

AUGUGUCCUCAGUGACAC

SEQ ID NO: 2660
UCUCAACGAUACUCAGAC

AUGUGUCCUCAGUGACAC

SEQ ID NO: 2661
UCUCAACGAUACUAAGAU

AUGUGUCCUCAGCGACAC

SEQ ID NO: 2662
UCUCAACGAUACUAAGAU

AUGUGUCCCCAGUGACAC

SEQ ID NO: 2663
UCUCAACGAUACUAAGAU

AUGUGUCCACAGUGACAC

SEQ ID NO: 2664
UCUCAACAAUACUCAGAC

AUGUGUCCCCAGUGACAC

SEQ ID NO: 2665
UCUCAACAAUACUAAGGC

AUGUGUCCCCAGUGACCC

SEQ ID NO: 2666
UCUCAAAGAUACUCAGAC

ACGUGUCCCCAGUGACAC

SEQ ID NO: 2667
UCUCAAAAAUACUCAGAC

AUGUGUCCUCAGUGACAC

SEQ ID NO: 2668
GCGAAACAACAGUCAGAC

AUGUGUCCCCAGUGACAC

SEQ ID NO: 2669
CCUCAACGAUAUUAAGAC

AUGUGUCCGCAGUGACAC

SEQ ID NO: 2670
AGACAUGUGUCCUCAGUG

ACAC

In some embodiments, the direct repeat sequence is a sequence of Table 3 or a portion of a sequence of Table 3. In some embodiments, the direct repeat sequence has at least 95% identity (e.g., at least 95%, 96%, 97%, 98% or 99% identity) to a sequence of Table 3 or a portion of a sequence of Table 3. In some embodiments, the direct repeat sequence has at least 90% identity (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity) to a sequence of Table 3 or a portion of a sequence of Table 3. In some embodiments, the direct repeat sequence is at least 90% identical to the reverse complement of any one of SEQ ID NOs: 2671-2673. In some embodiments, the direct repeat sequence is at least 95% identical to the reverse complement of any one of SEQ ID NOs: 2671-2673. In some embodiments, the direct repeat sequence is the reverse complement of any one of SEQ ID NOs: 2671-2673.

TABLE 3

Cas12il direct repeat sequences.

Sequence identifier
Direct Repeat Sequence

SEQ ID NO: 2671
GUUGGAAUGACUAAUUUU

UGUGCCCACCGUUGGCAC

SEQ ID NO: 2672
AAUUUUUGUGCCCAUCGU

UGGCAC

SEQ ID NO: 2673
AUUUUUGUGCCCAUCGUU

GGCAC

In some embodiments, the direct repeat sequence is a sequence of Table 4 or a portion of a sequence of Table 4. In some embodiments, the direct repeat sequence has at least 95% identity (e.g., at least 95%, 96%, 97%, 98% or 99% identity) to a sequence of Table 4 or a portion of a sequence of Table 4. In some embodiments, the direct repeat sequence has at least 90% identity (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity) to a sequence of Table 4 or a portion of a sequence of Table 4. In some embodiments, the direct repeat sequence is at least 90% identical to the reverse complement of any one of SEQ ID NOs: 2674-2676. In some embodiments, the direct repeat sequence is at least 95% identical to the reverse complement of any one of SEQ ID NOs: 2674-2676. In some embodiments, the direct repeat sequence is the reverse complement of any one of SEQ ID NOs: 2674-2676.

TABLE 4

Cas12i3 direct repeat sequences.

Sequence identifier
Direct Repeat Sequence

SEQ ID NO: 2674
CUAGCAAUGACCUAAUAG

UGUGUCCUUAGUUGACAU

SEQ ID NO: 2675
CCUACAAUACCUAAGAAA

UCCGUCCUAAGUUGACGG

SEQ ID NO: 2676
AUAGUGUGUCCUUAGUUG

ACAU

In some embodiments, a direct repeat sequence described herein comprises a uracil (U). In some embodiments, a direct repeat sequence described herein comprises a thymine (T). In some embodiments, a direct repeat sequence according to Tables 1-4 comprises a sequence comprising a thymine in one or more places indicated as uracil in Tables 1-4.

Spacer

In some embodiments, the RNA guide comprises a DNA targeting or spacer sequence. In some embodiments, the spacer sequence of the RNA guide has a length of between 12-100, 13-75, 14-50, or 15-30 nucleotides (e.g., 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 nucleotides) and is complementary a specific target sequence. In some embodiments, the spacer sequence is designed to be complementary to a specific DNA strand, e.g., of a genomic locus.

In some embodiments, the RNA guide spacer sequence is substantially identical to a complementary strand of a target sequence. In some embodiments, the RNA guide comprises a sequence having 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 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 99.5% sequence identity to a complementary strand of a reference nucleic acid sequence, e.g., target sequence. The percent identity between two such nucleic acids can be determined manually by inspection of the two optimally aligned nucleic acid sequences or by using software programs or algorithms (e.g., BLAST, ALIGN, CLUSTAL) using standard parameters.

In some embodiments, the RNA guide comprises a spacer sequence that has a length of between 12-100, 13-75, 14-50, or 15-30 nucleotides (e.g., 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 nucleotides) and at least 80%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% complementary to a target sequence. In some embodiments, the RNA guide comprises a sequence at least 80%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% complementary to a target DNA sequence. In some embodiments, the RNA guide comprises a sequence at least 80%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% complementary to a target genomic sequence.

In some embodiments, the RNA guide comprises a sequence, e.g., RNA sequence, that is a length of up to 50 and at least 80%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% complementary to a target sequence. In some embodiments, the RNA guide comprises a sequence at least 80%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% complementary to a target DNA sequence. In some embodiments, the RNA guide comprises a sequence at least 80%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% complementary to a target genomic sequence.

In some embodiments, the spacer sequence is or comprises a sequence of Table 5 or a portion of a sequence of Table 5. The target sequences listed in Table 5 are on the non-target strand of the BCL11A sequence. It should be understood that an indication of SEQ ID NOs: 1322-2632 should be considered as equivalent to a listing of SEQ ID NOs: 1322-2632, with each of the intervening numbers present in the listing, i.e., 1322, 1323, 1324, 1325, 1326, 1327, 1328, 1329, 1330, 1331, 1332, 1333, 1334, 1335, 1336, 1337, 1338, 1339, 1340, 1341, 1342, 1343, 1344, 1345, 1346, 1347, 1348, 1349, 1350, 1351, 1352, 1353, 1354, 1355, 1356, 1357, 1358, 1359, 1360, 1361, 1362, 1363, 1364, 1365, 1366, 1367, 1368, 1369, 1370, 1371, 1372, 1373, 1374, 1375, 1376, 1377, 1378, 1379, 1380, 1381, 1382, 1383, 1384, 1385, 1386, 1387, 1388, 1389, 1390, 1391, 1392, 1393, 1394, 1395, 1396, 1397, 1398, 1399, 1400, 1401, 1402, 1403, 1404, 1405, 1406, 1407, 1408, 1409, 1410, 1411, 1412, 1413, 1414, 1415, 1416, 1417, 1418, 1419, 1420, 1421, 1422, 1423, 1424, 1425, 1426, 1427, 1428, 1429, 1430, 1431, 1432, 1433, 1434, 1435, 1436, 1437, 1438, 1439, 1440, 1441, 1442, 1443, 1444, 1445, 1446, 1447, 1448, 1449, 1450, 1451, 1452, 1453, 1454, 1455, 1456, 1457, 1458, 1459, 1460, 1461, 1462, 1463, 1464, 1465, 1466, 1467, 1468, 1469, 1470, 1471, 1472, 1473, 1474, 1475, 1476, 1477, 1478, 1479, 1480, 1481, 1482, 1483, 1484, 1485, 1486, 1487, 1488, 1489, 1490, 1491, 1492, 1493, 1494, 1495, 1496, 1497, 1498, 1499, 1500, 1501, 1502, 1503, 1504, 1505, 1506, 1507, 1508, 1509, 1510, 1511, 1512, 1513, 1514, 1515, 1516, 1517, 1518, 1519, 1520, 1521, 1522, 1523, 1524, 1525, 1526, 1527, 1528, 1529, 1530, 1531, 1532, 1533, 1534, 1535, 1536, 1537, 1538, 1539, 1540, 1541, 1542, 1543, 1544, 1545, 1546, 1547, 1548, 1549, 1550, 1551, 1552, 1553, 1554, 1555, 1556, 1557, 1558, 1559, 1560, 1561, 1562, 1563, 1564, 1565, 1566, 1567, 1568, 1569, 1570, 1571, 1572, 1573, 1574, 1575, 1576, 1577, 1578, 1579, 1580, 1581, 1582, 1583, 1584, 1585, 1586, 1587, 1588, 1589, 1590, 1591, 1592, 1593, 1594, 1595, 1596, 1597, 1598, 1599, 1600, 1601, 1602, 1603, 1604, 1605, 1606, 1607, 1608, 1609, 1610, 1611, 1612, 1613, 1614, 1615, 1616, 1617, 1618, 1619, 1620, 1621, 1622, 1623, 1624, 1625, 1626, 1627, 1628, 1629, 1630, 1631, 1632, 1633, 1634, 1635, 1636, 1637, 1638, 1639, 1640, 1641, 1642, 1643, 1644, 1645, 1646, 1647, 1648, 1649, 1650, 1651, 1652, 1653, 1654, 1655, 1656, 1657, 1658, 1659, 1660, 1661, 1662, 1663, 1664, 1665, 1666, 1667, 1668, 1669, 1670, 1671, 1672, 1673, 1674, 1675, 1676, 1677, 1678, 1679, 1680, 1681, 1682, 1683, 1684, 1685, 1686, 1687, 1688, 1689, 1690, 1691, 1692, 1693, 1694, 1695, 1696, 1697, 1698, 1699, 1700, 1701, 1702, 1703, 1704, 1705, 1706, 1707, 1708, 1709, 1710, 1711, 1712, 1713, 1714, 1715, 1716, 1717, 1718, 1719, 1720, 1721, 1722, 1723, 1724, 1725, 1726, 1727, 1728, 1729, 1730, 1731, 1732, 1733, 1734, 1735, 1736, 1737, 1738, 1739, 1740, 1741, 1742, 1743, 1744, 1745, 1746, 1747, 1748, 1749, 1750, 1751, 1752, 1753, 1754, 1755, 1756, 1757, 1758, 1759, 1760, 1761, 1762, 1763, 1764, 1765, 1766, 1767, 1768, 1769, 1770, 1771, 1772, 1773, 1774, 1775, 1776, 1777, 1778, 1779, 1780, 1781, 1782, 1783, 1784, 1785, 1786, 1787, 1788, 1789, 1790, 1791, 1792, 1793, 1794, 1795, 1796, 1797, 1798, 1799, 1800, 1801, 1802, 1803, 1804, 1805, 1806, 1807, 1808, 1809, 1810, 1811, 1812, 1813, 1814, 1815, 1816, 1817, 1818, 1819, 1820, 1821, 1822, 1823, 1824, 1825, 1826, 1827, 1828, 1829, 1830, 1831, 1832, 1833, 1834, 1835, 1836, 1837, 1838, 1839, 1840, 1841, 1842, 1843, 1844, 1845, 1846, 1847, 1848, 1849, 1850, 1851, 1852, 1853, 1854, 1855, 1856, 1857, 1858, 1859, 1860, 1861, 1862, 1863, 1864, 1865, 1866, 1867, 1868, 1869, 1870, 1871, 1872, 1873, 1874, 1875, 1876, 1877, 1878, 1879, 1880, 1881, 1882, 1883, 1884, 1885, 1886, 1887, 1888, 1889, 1890, 1891, 1892, 1893, 1894, 1895, 1896, 1897, 1898, 1899, 1900, 1901, 1902, 1903, 1904, 1905, 1906, 1907, 1908, 1909, 1910, 1911, 1912, 1913, 1914, 1915, 1916, 1917, 1918, 1919, 1920, 1921, 1922, 1923, 1924, 1925, 1926, 1927, 1928, 1929, 1930, 1931, 1932, 1933, 1934, 1935, 1936, 1937, 1938, 1939, 1940, 1941, 1942, 1943, 1944, 1945, 1946, 1947, 1948, 1949, 1950, 1951, 1952, 1953, 1954, 1955, 1956, 1957, 1958, 1959, 1960, 1961, 1962, 1963, 1964, 1965, 1966, 1967, 1968, 1969, 1970, 1971, 1972, 1973, 1974, 1975, 1976, 1977, 1978, 1979, 1980, 1981, 1982, 1983, 1984, 1985, 1986, 1987, 1988, 1989, 1990, 1991, 1992, 1993, 1994, 1995, 1996, 1997, 1998, 1999, 2000, 2001, 2002, 2003, 2004, 2005, 2006, 2007, 2008, 2009, 2010, 2011, 2012, 2013, 2014, 2015, 2016, 2017, 2018, 2019, 2020, 2021, 2022, 2023, 2024, 2025, 2026, 2027, 2028, 2029, 2030, 2031, 2032, 2033, 2034, 2035, 2036, 2037, 2038, 2039, 2040, 2041, 2042, 2043, 2044, 2045, 2046, 2047, 2048, 2049, 2050, 2051, 2052, 2053, 2054, 2055, 2056, 2057, 2058, 2059, 2060, 2061, 2062, 2063, 2064, 2065, 2066, 2067, 2068, 2069, 2070, 2071, 2072, 2073, 2074, 2075, 2076, 2077, 2078, 2079, 2080, 2081, 2082, 2083, 2084, 2085, 2086, 2087, 2088, 2089, 2090, 2091, 2092, 2093, 2094, 2095, 2096, 2097, 2098, 2099, 2100, 2101, 2102, 2103, 2104, 2105, 2106, 2107, 2108, 2109, 2110, 2111, 2112, 2113, 2114, 2115, 2116, 2117, 2118, 2119, 2120, 2121, 2122, 2123, 2124, 2125, 2126, 2127, 2128, 2129, 2130, 2131, 2132, 2133, 2134, 2135, 2136, 2137, 2138, 2139, 2140, 2141, 2142, 2143, 2144, 2145, 2146, 2147, 2148, 2149, 2150, 2151, 2152, 2153, 2154, 2155, 2156, 2157, 2158, 2159, 2160, 2161, 2162, 2163, 2164, 2165, 2166, 2167, 2168, 2169, 2170, 2171, 2172, 2173, 2174, 2175, 2176, 2177, 2178, 2179, 2180, 2181, 2182, 2183, 2184, 2185, 2186, 2187, 2188, 2189, 2190, 2191, 2192, 2193, 2194, 2195, 2196, 2197, 2198, 2199, 2200, 2201, 2202, 2203, 2204, 2205, 2206, 2207, 2208, 2209, 2210, 2211, 2212, 2213, 2214, 2215, 2216, 2217, 2218, 2219, 2220, 2221, 2222, 2223, 2224, 2225, 2226, 2227, 2228, 2229, 2230, 2231, 2232, 2233, 2234, 2235, 2236, 2237, 2238, 2239, 2240, 2241, 2242, 2243, 2244, 2245, 2246, 2247, 2248, 2249, 2250, 2251, 2252, 2253, 2254, 2255, 2256, 2257, 2258, 2259, 2260, 2261, 2262, 2263, 2264, 2265, 2266, 2267, 2268, 2269, 2270, 2271, 2272, 2273, 2274, 2275, 2276, 2277, 2278, 2279, 2280, 2281, 2282, 2283, 2284, 2285, 2286, 2287, 2288, 2289, 2290, 2291, 2292, 2293, 2294, 2295, 2296, 2297, 2298, 2299, 2300, 2301, 2302, 2303, 2304, 2305, 2306, 2307, 2308, 2309, 2310, 2311, 2312, 2313, 2314, 2315, 2316, 2317, 2318, 2319, 2320, 2321, 2322, 2323, 2324, 2325, 2326, 2327, 2328, 2329, 2330, 2331, 2332, 2333, 2334, 2335, 2336, 2337, 2338, 2339, 2340, 2341, 2342, 2343, 2344, 2345, 2346, 2347, 2348, 2349, 2350, 2351, 2352, 2353, 2354, 2355, 2356, 2357, 2358, 2359, 2360, 2361, 2362, 2363, 2364, 2365, 2366, 2367, 2368, 2369, 2370, 2371, 2372, 2373, 2374, 2375, 2376, 2377, 2378, 2379, 2380, 2381, 2382, 2383, 2384, 2385, 2386, 2387, 2388, 2389, 2390, 2391, 2392, 2393, 2394, 2395, 2396, 2397, 2398, 2399, 2400, 2401, 2402, 2403, 2404, 2405, 2406, 2407, 2408, 2409, 2410, 2411, 2412, 2413, 2414, 2415, 2416, 2417, 2418, 2419, 2420, 2421, 2422, 2423, 2424, 2425, 2426, 2427, 2428, 2429, 2430, 2431, 2432, 2433, 2434, 2435, 2436, 2437, 2438, 2439, 2440, 2441, 2442, 2443, 2444, 2445, 2446, 2447, 2448, 2449, 2450, 2451, 2452, 2453, 2454, 2455, 2456, 2457, 2458, 2459, 2460, 2461, 2462, 2463, 2464, 2465, 2466, 2467, 2468, 2469, 2470, 2471, 2472, 2473, 2474, 2475, 2476, 2477, 2478, 2479, 2480, 2481, 2482, 2483, 2484, 2485, 2486, 2487, 2488, 2489, 2490, 2491, 2492, 2493, 2494, 2495, 2496, 2497, 2498, 2499, 2500, 2501, 2502, 2503, 2504, 2505, 2506, 2507, 2508, 2509, 2510, 2511, 2512, 2513, 2514, 2515, 2516, 2517, 2518, 2519, 2520, 2521, 2522, 2523, 2524, 2525, 2526, 2527, 2528, 2529, 2530, 2531, 2532, 2533, 2534, 2535, 2536, 2537, 2538, 2539, 2540, 2541, 2542, 2543, 2544, 2545, 2546, 2547, 2548, 2549, 2550, 2551, 2552, 2553, 2554, 2555, 2556, 2557, 2558, 2559, 2560, 2561, 2562, 2563, 2564, 2565, 2566, 2567, 2568, 2569, 2570, 2571, 2572, 2573, 2574, 2575, 2576, 2577, 2578, 2579, 2580, 2581, 2582, 2583, 2584, 2585, 2586, 2587, 2588, 2589, 2590, 2591, 2592, 2593, 2594, 2595, 2596, 2597, 2598, 2599, 2600, 2601, 2602, 2603, 2604, 2605, 2606, 2607, 2608, 2609, 2610, 2611, 2612, 2613, 2614, 2615, 2616, 2617, 2618, 2619, 2620, 2621, 2622, 2623, 2624, 2625, 2626, 2627, 2628, 2629, 2630, 2631, and 2632.

The spacer sequence can comprise nucleotide 1 through nucleotide 16 of any one of SEQ ID NOs: 1322-2632. The spacer sequence can comprise nucleotide 1 through nucleotide 17 of any one of SEQ ID NOs: 1322-2632. The spacer sequence can comprise nucleotide 1 through nucleotide 18 of any one of SEQ ID NOs: 1322-2632. The spacer sequence can comprise nucleotide 1 through nucleotide 19 of any one of SEQ ID NOs: 1322-2632. The spacer sequence can comprise nucleotide 1 through nucleotide 20 of any one of SEQ ID NOs: 1322-2632. The spacer sequence can comprise nucleotide 1 through nucleotide 21 of any one of SEQ ID NOs: 1322-2632. The spacer sequence can comprise nucleotide 1 through nucleotide 22 of any one of SEQ ID NOs: 1322-2632. The spacer sequence can comprise nucleotide 1 through nucleotide 23 of any one of SEQ ID NOs: 1322-2632. The spacer sequence can comprise nucleotide 1 through nucleotide 24 of any one of SEQ ID NOs: 1322-2632. The spacer sequence can comprise nucleotide 1 through nucleotide 25 of any one of SEQ ID NOs: 1322-2632. The spacer sequence can comprise nucleotide 1 through nucleotide 26 of any one of SEQ ID NOs: 1322-2632. The spacer sequence can comprise nucleotide 1 through nucleotide 27 of any one of SEQ ID NOs: 1322-2632. The spacer sequence can comprise nucleotide 1 through nucleotide 28 of any one of SEQ ID NOs: 1322-2632. The spacer sequence can comprise nucleotide 1 through nucleotide 29 of any one of SEQ ID NOs: 1322-1425 and 1427-2632. The spacer sequence can comprise nucleotide 1 through nucleotide 30 of any one of SEQ ID NOs: 1322-1425 and 1427-2632.

In some embodiments, the spacer sequence has or comprises a sequence having at least 90% identity (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity) to a sequence of Table 5 or a portion of a sequence of Table 5. The spacer sequence can have or comprise a sequence having at least 90% identity to a sequence comprising nucleotide 1 through nucleotide 16 of any one of SEQ ID NOs: 1322-2632. The spacer sequence can have or comprise a sequence having at least 90% identity to a sequence comprising nucleotide 1 through nucleotide 17 of any one of SEQ ID NOs: 1322-2632. The spacer sequence can have or comprise a sequence having at least 90% identity to a sequence comprising nucleotide 1 through nucleotide 18 of any one of SEQ ID NOs: 1322-2632. The spacer sequence can have or comprise a sequence having at least 90% identity to a sequence comprising nucleotide 1 through nucleotide 19 of any one of SEQ ID NOs: 1322-2632. The spacer sequence can have or comprise a sequence having at least 90% identity to a sequence comprising nucleotide 1 through nucleotide 20 of any one of SEQ ID NOs: 1322-2632. The spacer sequence can have or comprise a sequence having at least 90% identity to a sequence comprising nucleotide 1 through nucleotide 21 of any one of SEQ ID NOs: 1322-2632. The spacer sequence can have or comprise a sequence having at least 90% identity to a sequence comprising nucleotide 1 through nucleotide 22 of any one of SEQ ID NOs: 1322-2632. The spacer sequence can have or comprise a sequence having at least 90% identity to a sequence comprising nucleotide 1 through nucleotide 23 of any one of SEQ ID NOs: 1322-2632. The spacer sequence can have or comprise a sequence having at least 90% identity to a sequence comprising nucleotide 1 through nucleotide 24 of any one of SEQ ID NOs: 1322-2632. The spacer sequence can have or comprise a sequence having at least 90% identity to a sequence comprising nucleotide 1 through nucleotide 25 of any one of SEQ ID NOs: 1322-2632. The spacer sequence can have or comprise a sequence having at least 90% identity to a sequence comprising nucleotide 1 through nucleotide 26 of any one of SEQ ID NOs: 1322-2632. The spacer sequence can have or comprise a sequence having at least 90% identity to a sequence comprising nucleotide 1 through nucleotide 27 of any one of SEQ ID NOs: 1322-2632. The spacer sequence can have or comprise a sequence having at least 90% identity to a sequence comprising nucleotide 1 through nucleotide 28 of any one of SEQ ID NOs: 1322-2632. The spacer sequence can have or comprise a sequence having at least 90% identity to a sequence comprising nucleotide 1 through nucleotide 29 of any one of SEQ ID NOs: 1322-1425 and 1427-2632. The spacer sequence can have or comprise a sequence having at least 90% identity to a sequence comprising nucleotide 1 through nucleotide 30 of any one of SEQ ID NOs: 1322-1425 and 1427-2632.

TABLE 5

Target and spacer sequences

SEQ

SEQ

ID

ID

BCL11A
strand
PAM
NO
target sequence
NO
spacer sequence

BCL11A_
−
CTTA
11
GACATAACACACCAGGG
1322
GACAUAACACACCAGGGUC

enhancer_

TCAATACAACTTT

AAUACAACUUU

region

BCL11A_
−
CTTT
12
GAAGCTAGTCTAGTGCA
1323
GAAGCUAGUCUAGUGCAAG

enhancer_

AGCTAACAGTTGC

CUAACAGUUGC

region

BCL11A_
−
TTTG
13
AAGCTAGTCTAGTGCAA
1324
AAGCUAGUCUAGUGCAAGC

enhancer_

GCTAACAGTTGCT

UAACAGUUGCU

region

BCL11A_
−
GTTG
14
CTTTTATCACAGGCTCC
1325
CUUUUAUCACAGGCUCCAG

enhancer_

AGGAAGGGTTTGG

GAAGGGUUUGG

region

BCL11A_
−
CTTT
15
TATCACAGGCTCCAGGA
1326
UAUCACAGGCUCCAGGAAG

enhancer_

AGGGTTTGGCCTC

GGUUUGGCCUC

region

BCL11A_
−
TTTA
16
TCACAGGCTCCAGGAAG
1327
UCACAGGCUCCAGGAAGGG

enhancer_

GGTTTGGCCTCTG

UUUGGCCUCUG

region

BCL11A_
−
GTTT
17
GGCCTCTGATTAGGGTG
1328
GGCCUCUGAUUAGGGUGGG

enhancer_

GGGGCGTGGGTGG

GGCGUGGGUGG

region

BCL11A_
−
TTTG
18
GCCTCTGATTAGGGTGG
1329
GCCUCUGAUUAGGGUGGGG

enhancer_

GGGCGTGGGTGGG

GCGUGGGUGGG

region

BCL11A_
−
TTTT
19
ATCACAGGCTCCAGGAA
1330
AUCACAGGCUCCAGGAAGG

enhancer_

GGGTTTGGCCTCT

GUUUGGCCUCU

region

BCL11A_
+
CTTC
20
TACCCCACCCACGCCCC
1331
UACCCCACCCACGCCCCCA

enhancer_

CACCCTAATCAGA

CCCUAAUCAGA

region

BCL11A_
+
CTTC
21
CTGGAGCCTGTGATAAA
1332
CUGGAGCCUGUGAUAAAAG

enhancer_

AGCAACTGTTAGC

CAACUGUUAGC

region

BCL11A_
+
GTTA
22
GCTTGCACTAGACTAGC
1333
GCUUGCACUAGACUAGCUU

enhancer_

TTCAAAGTTGTAT

CAAAGUUGUAU

region

BCL11A_
+
CTTG
23
CACTAGACTAGCTTCAA
1334
CACUAGACUAGCUUCAAAG

enhancer_

AGTTGTATTGACC

UUGUAUUGACC

region

BCL11A_
+
CTTC
24
AAAGTTGTATTGACCCT
1335
AAAGUUGUAUUGACCCUGG

enhancer_

GGTGTGTTATGTC

UGUGUUAUGUC

region

BCL11A_
+
GTTG
25
TATTGACCCTGGTGTGT
1336
UAUUGACCCUGGUGUGUUA

enhancer_

TATGTCTAAGAGT

UGUCUAAGAGU

region

BCL11A_
+
ATTG
26
ACCCTGGTGTGTTATGT
1337
ACCCUGGUGUGUUAUGUCU

enhancer_

CTAAGAGTAGATG

AAGAGUAGAUG

region

BCL11A_
−
ATTA
27
GGGTGGGGGCGTGGGTG
1338
GGGUGGGGGCGUGGGUGGG

enhancer_

GGGTAGAAGAGGA

GUAGAAGAGGA

region

BCL11A_
−
TTTT
28
TTTGCTTAAAAAAAAGC
1339
UUUGCUUAAAAAAAAGCCA

exon_1

CATGACGGCTCTC

UGACGGCUCUC

BCL11A_
−
TTTT
29
TTTTTTTTTGCTTAAAA
1340
UUUUUUUUUGCUUAAAAAA

exon 1

AAAAGCCATGACG

AAGCCAUGACG

BCL11A_
−
TTTT
30
TTTTTTTTGCTTAAAAA
1341
UUUUUUUUGCUUAAAAAAA

exon_1

AAAGCCATGACGG

AGCCAUGACGG

BCL11A_
−
TTTT
31
TTTTTTTGCTTAAAAAA
1342
UUUUUUUGCUUAAAAAAAA

exon_1

AAGCCATGACGGC

GCCAUGACGGC

BCL11A_
−
TTTT
32
TTTTTTGCTTAAAAAAA
1343
UUUUUUGCUUAAAAAAAAG

exon_1

AGCCATGACGGCT

CCAUGACGGCU

BCL11A_
−
TTTT
33
TTTTTGCTTAAAAAAAA
1344
UUUUUGCUUAAAAAAAAGC

exon_1

GCCATGACGGCTC

CAUGACGGCUC

BCL11A_
−
TTTT
34
TTTTGCTTAAAAAAAAG
1345
UUUUGCUUAAAAAAAAGCC

exon_1

CCATGACGGCTCT

AUGACGGCUCU

BCL11A_
−
TTTT
35
TTGCTTAAAAAAAAGCC
1346
UUGCUUAAAAAAAAGCCAU

exon_1

ATGACGGCTCTCC

GACGGCUCUCC

BCL11A_
+
CTTT
36
TGACATCCAAAATAAAT
1347
UGACAUCCAAAAUAAAUUA

exon_1

TAGAAATAATACA

GAAAUAAUACA

BCL11A_
−
TTTT
37
GCTTAAAAAAAAGCCAT
1348
GCUUAAAAAAAAGCCAUGA

exon_1

GACGGCTCTCCCA

CGGCUCUCCCA

BCL11A_
−
TTTG
38
CTTAAAAAAAAGCCATG
1349
CUUAAAAAAAAGCCAUGAC

exon_1

ACGGCTCTCCCAC

GGCUCUCCCAC

BCL11A_
−
CTTA
39
AAAAAAAGCCATGACGG
1350
AAAAAAAGCCAUGACGGCU

exon_1

CTCTCCCACAATT

CUCCCACAAUU

BCL11A_
−
ATTC
40
ATCTTCCCTGCGCCATC
135
AUCUUCCCUGCGCCAUCUU

exon_1

TTTGTATTATTTC

UGUAUUAUUUC

BCL11A_
−
CTTC
41
CCTGCGCCATCTTTGTA
1352
CCUGCGCCAUCUUUGUAUU

exon_1

TTATTTCTAATTT

AUUUCUAAUUU

BCL11A_
−
CTTT
42
GTATTATTTCTAATTTA
1353
GUAUUAUUUCUAAUUUAUU

exon_1

TTTTGGATGTCAA

UUGGAUGUCAA

BCL11A_
−
TTTT
43
TTTTTTTTTTGCTTAAA
1354
UUUUUUUUUUGCUUAAAAA

exon_1

AAAAAGCCATGAC

AAAGCCAUGAC

BCL11A_
−
TTTT
44
TGCTTAAAAAAAAGCCA
1355
UGCUUAAAAAAAAGCCAUG

exon 1

TGACGGCTCTCCC

ACGGCUCUCCC

BCL11A_
−
TTTT
45
TTTTTTTTTTTGCTTAA
1356
UUUUUUUUUUUGCUUAAAA

exon_1

AAAAAAGCCATGA

AAAAGCCAUGA

BCL11A_
−
TTTT
46
TTTTTTTTTTTTTTTTT
1357
UUUUUUUUUUUUUUUUUUU

exon 1

TTTTTGCTTAAAA

UUUGCUUAAAA

BCL11A_
−
TTTT
47
TTTTTTTTTTTTTGCTT
1358
UUUUUUUUUUUUUGCUUAA

exon_1

AAAAAAAAGCCAT

AAAAAAGCCAU

BCL11A_
−
TTTG
48
CCATTTTTTTCATCTCT
1359
CCAUUUUUUUCAUCUCUCU

exon_1

CTCTCTCTCTCTC

CUCUCUCUCUC

BCL11A_
−
ATTT
49
TTTTCATCTCTCTCTCT
1360
UUUUCAUCUCUCUCUCUCU

exon_1

CTCTCTCCCTCTA

CUCUCCCUCUA

BCL11A_
−
TTTT
50
TTTCATCTCTCTCTCTC
1361
UUUCAUCUCUCUCUCUCUC

exon_1

TCTCTCCCTCTAT

UCUCCCUCUAU

BCL11A_
−
TTTT
51
TTCATCTCTCTCTCTCT
1362
UUCAUCUCUCUCUCUCUCU

exon_1

CTCTCCCTCTATC

CUCCCUCUAUC

BCL11A_
−
TTTT
52
TCATCTCTCTCTCTCTC
1363
UCAUCUCUCUCUCUCUCUC

exon_1

TCTCCCTCTATCT

UCCCUCUAUCU

BCL11A_
−
TTTT
53
CATCTCTCTCTCTCTCT
1364
CAUCUCUCUCUCUCUCUCU

exon_1

CTCCCTCTATCTC

CCCUCUAUCUC

BCL11A_
−
TTTC
54
ATCTCTCTCTCTCTCTC
1365
AUCUCUCUCUCUCUCUCUC

exon_1

TCCCTCTATCTCT

CCUCUAUCUCU

BCL11A_
−
CTTC
55
TCTCTCTCTCCCTCTTT
1366
UCUCUCUCUCCCUCUUUUU

exon_1

TTTTTTTTTTTTT

UUUUUUUUUUU

BCL11A_
−
TTTG
56
TATTATTTCTAATTTAT
1367
UAUUAUUUCUAAUUUAUUU

exon_1

TTTGGATGTCAAA

UGGAUGUCAAA

BCL11A_
−
TTTT
57
TTTTTTTTTTTTTTTTT
1368
UUUUUUUUUUUUUUUUUUU

exon_1

TTGCTTAAAAAAA

GCUUAAAAAAA

BCL11A_
−
TTTT
58
TTTTTTTTTTTTTTTTT
1369
UUUUUUUUUUUUUUUUUUG

exon 1

TGCTTAAAAAAAA

CUUAAAAAAAA

BCL11A_
−
TTTT
59
TTTTTTTTTTTTTTTTT
1370
UUUUUUUUUUUUUUUUUGC

exon_1

GCTTAAAAAAAAG

UUAAAAAAAAG

BCL11A_
−
TTTT
60
TTTTTTTTTTTTTTTTG
1371
UUUUUUUUUUUUUUUUGCU

exon_1

CTTAAAAAAAAGC

UAAAAAAAAGC

BCL11A_
−
TTTT
61
TTTTTTTTTTTTTTTGC
1372
UUUUUUUUUUUUUUUGCUU

exon_1

TTAAAAAAAAGCC

AAAAAAAAGCC

BCL11A_
−
TTTT
62
TTTTTTTTTTTTTTGCT
1373
UUUUUUUUUUUUUUGCUUA

exon_1

TAAAAAAAAGCCA

AAAAAAAGCCA

BCL11A_
−
TTTT
63
TTTTTTTTTTTTGCTTA
1374
UUUUUUUUUUUUGCUUAAA

exon_1

AAAAAAAGCCATG

AAAAAGCCAUG

BCL11A_
−
ATTA
64
TTTCTAATTTATTTTGG
1375
UUUCUAAUUUAUUUUGGAU

exon_1

ATGTCAAAAGGCA

GUCAAAAGGCA

BCL11A_
−
TTTT
65
CTCTGGAGTCTCCTTCT
1376
CUCUGGAGUCUCCUUCUUU

exon_1

TTCTAACCCGGCT

CUAACCCGGCU

BCL11A_
−
TTTC
66
TAATTTATTTTGGATGT
1377
UAAUUUAUUUUGGAUGUCA

exon_1

CAAAAGGCACTGA

AAAGGCACUGA

BCL11A_
+
GTTA
67
CTTACGCGAGAATTCCC
1378
CUUACGCGAGAAUUCCCGU

exon_1

GTTTGCTTAAGTG

UUGCUUAAGUG

BCL11A_
+
CTTA
68
CGCGAGAATTCCCGTTT
1379
CGCGAGAAUUCCCGUUUGC

exon_1

GCTTAAGTGCTGG

UUAAGUGCUGG

BCL11A_
+
ATTC
69
CCGTTTGCTTAAGTGCT
1380
CCGUUUGCUUAAGUGCUGG

exon_1

GGGGTTTGCCTTG

GGUUUGCCUUG

BCL11A_
+
GTTT
70
GCTTAAGTGCTGGGGTT
1381
GCUUAAGUGCUGGGGUUUG

exon_1

TGCCTTGCTTGCG

CCUUGCUUGCG

BCL11A_
+
TTTG
71
CTTAAGTGCTGGGGTTT
1382
CUUAAGUGCUGGGGUUUGC

exon_1

GCCTTGCTTGCGG

CUUGCUUGCGG

BCL11A_
+
CTTA
72
AGTGCTGGGGTTTGCCT
1383
AGUGCUGGGGUUUGCCUUG

exon_1

TGCTTGCGGCGAG

CUUGCGGCGAG

BCL11A_
+
GTTT
73
GCCTTGCTTGCGGCGAG
1384
GCCUUGCUUGCGGCGAGAC

exon_1

ACATGGTGGGCTG

AUGGUGGGCUG

BCL11A_
+
TTTG
74
CCTTGCTTGCGGCGAGA
1385
CCUUGCUUGCGGCGAGACA

exon_1

CATGGTGGGCTGC

UGGUGGGCUGC

BCL11A_
+
CTTG
75
CTTGCGGCGAGACATGG
1386
CUUGCGGCGAGACAUGGUG

exon_1

TGGGCTGCGGGGC

GGCUGCGGGGC

BCL11A_
+
CTTG
76
CGGCGAGACATGGTGGG
1387
CGGCGAGACAUGGUGGGCU

exon_1

CTGCGGGGCGGGC

GCGGGGCGGGC

BCL11A_
+
GTTC
77
ACATCGGGAGAGCCGGG
1388
ACAUCGGGAGAGCCGGGUU

exon_1

TTAGAAAGAAGGA

AGAAAGAAGGA

BCL11A_
+
GTTA
78
GAAAGAAGGAGACTCCA
1389
GAAAGAAGGAGACUCCAGA

exon_1

GAGAAAATATCTT

GAAAAUAUCUU

BCL11A_
+
CTTC
79
ATCAGTGCCTTTTGACA
1390
AUCAGUGCCUUUUGACAUC

exon_1

TCCAAAATAAATT

CAAAAUAAAUU

BCL11A_
+
ATTG
80
TGGGAGAGCCGTCATGG
1391
UGGGAGAGCCGUCAUGGCU

exon_1

CTTTTTTTTAAGC

UUUUUUUAAGC

BCL11A_
+
TTTT
81
GACATCCAAAATAAATT
1392
GACAUCCAAAAUAAAUUAG

exon_1

AGAAATAATACAA

AAAUAAUACAA

BCL11A_
+
ATTG
82
GGTTACTTACGCGAGAA
1393
GGUUACUUACGCGAGAAUU

exon_1

TTCCCGTTTGCTT

CCCGUUUGCUU

BCL11A_
+
ATTA
83
TTGGGTTACTTACGCGA
1394
UUGGGUUACUUACGCGAGA

exon_1

GAATTCCCGTTTG

AUUCCCGUUUG

BCL11A_
+
ATTA
84
CTATTATTGGGTTACTT
1395
CUAUUAUUGGGUUACUUAC

exon_1

ACGCGAGAATTCC

GCGAGAAUUCC

BCL11A_
+
ATTA
85
TTACTATTATTGGGTTA
1396
UUACUAUUAUUGGGUUACU

exon_1

CTTACGCGAGAAT

UACGCGAGAAU

BCL11A_
−
ATTT
86
ATTTTGGATGTCAAAAG
1397
AUUUUGGAUGUCAAAAGGC

exon_1

GCACTGATGAAGA

ACUGAUGAAGA

BCL11A_
−
TTTA
87
TTTTGGATGTCAAAAGG
1398
UUUUGGAUGUCAAAAGGCA

exon 1

CACTGATGAAGAT

CUGAUGAAGAU

BCL11A_
−
ATTT
88
TGGATGTCAAAAGGCAC
1399
UGGAUGUCAAAAGGCACUG

exon_1

TGATGAAGATATT

AUGAAGAUAUU

BCL11A_
−
TTTT
89
GGATGTCAAAAGGCACT
1400
GGAUGUCAAAAGGCACUGA

exon_1

GATGAAGATATTT

UGAAGAUAUUU

BCL11A_
−
TTTG
90
GATGTCAAAAGGCACTG
1401
GAUGUCAAAAGGCACUGAU

exon_1

ATGAAGATATTTT

GAAGAUAUUUU

BCL11A_
−
ATTT
91
TCTCTGGAGTCTCCTTC
1402
UCUCUGGAGUCUCCUUCUU

exon_1

TTTCTAACCCGGC

UCUAACCCGGC

BCL11A_
−
TTTT
92
GCCATTTTTTTCATCTC
1403
GCCAUUUUUUUCAUCUCUC

exon_1

TCTCTCTCTCTCT

UCUCUCUCUCU

BCL11A_
−
ATTT
93
CTAATTTATTTTGGATG
1404
CUAAUUUAUUUUGGAUGUC

exon_1

TCAAAAGGCACTG

AAAAGGCACUG

BCL11A_
−
TTTC
94
TCTGGAGTCTCCTTCTT
1405
UCUGGAGUCUCCUUCUUUC

exon_1

TCTAACCCGGCTC

UAACCCGGCUC

BCL11A_
−
CTTT
95
CTAACCCGGCTCTCCCG
1406
CUAACCCGGCUCUCCCGAU

exon_1

ATGTGAACCGAGC

GUGAACCGAGC

BCL11A_
−
TTTC
96
TAACCCGGCTCTCCCGA
1407
UAACCCGGCUCUCCCGAUG

exon_1

TGTGAACCGAGCC

UGAACCGAGCC

BCL11A_
−
CTTA
97
AGCAAACGGGAATTCTC
1408
AGCAAACGGGAAUUCUCGC

exon_1

GCGTAAGTAACCC

GUAAGUAACCC

BCL11A_
−
ATTC
98
TCGCGTAAGTAACCCAA
1409
UCGCGUAAGUAACCCAAUA

exon_1

TAATAGTAATAAT

AUAGUAAUAAU

BCL11A_
+
ATTA
99
TTAATAATTATTATTAC
1410
UUAAUAAUUAUUAUUACUA

exon_1

TATTATTGGGTTA

UUAUUGGGUUA

BCL11A_
+
ATTA
100
ATAATTATTATTACTAT
1411
AUAAUUAUUAUUACUAUUA

exon_1

TATTGGGTTACTT

UUGGGUUACUU

BCL11A_
+
ATTA
101
TTATTACTATTATTGGG
1412
UUAUUACUAUUAUUGGGUU

exon_1

TTACTTACGCGAG

ACUUACGCGAG

BCL11A_
−
CTTC
102
TTTCTAACCCGGCTCTC
1413
UUUCUAACCCGGCUCUCCC

exon_1

CCGATGTGAACCG

GAUGUGAACCG

BCL11A_
−
CTTT
103
TGCCATTTTTTTCATCT
1414
UGCCAUUUUUUUCAUCUCU

exon_1

CTCTCTCTCTCTC

CUCUCUCUCUC

BCL11A_
+
ATTA
104
GAAATAATACAAAGATG
1415
GAAAUAAUACAAAGAUGGC

exon_1

GCGCAGGGAAGAT

GCAGGGAAGAU

BCL11A_
−
CTTG
105
AACTTGCAGCTCAGGGG
1416
AACUUGCAGCUCAGGGGGG

exon_1

GGCTTTTGCCATT

CUUUUGCCAUU

BCL11A_
−
CTTG
106
CAGCTCAGGGGGGCTTT
1417
CAGCUCAGGGGGGCUUUUG

exon_1

TGCCATTTTTTTC

CCAUUUUUUUC

BCL11A_
+
TTTT
107
TTTTAAGCAAAAAAAAA
1418
UUUUAAGCAAAAAAAAAAA

exon_1

AAAAAAAAAAAAA

AAAAAAAAAAA

BCL11A_
+
TTTT
108
TTTAAGCAAAAAAAAAA
1419
UUUAAGCAAAAAAAAAAAA

exon_1

AAAAAAAAAAAAA

AAAAAAAAAAA

BCL11A_
+
TTTT
109
TTAAGCAAAAAAAAAAA
1420
UUAAGCAAAAAAAAAAAAA

exon_1

AAAAAAAAAAAAA

AAAAAAAAAAA

BCL11A_
+
TTTT
110
TAAGCAAAAAAAAAAAA
1421
UAAGCAAAAAAAAAAAAAA

exon_1

AAAAAAAAAAAAA

AAAAAAAAAAA

BCL11A_
+
TTTG
111
ACATCCAAAATAAATTA
1422
ACAUCCAAAAUAAAUUAGA

exon_1

GAAATAATACAAA

AAUAAUACAAA

BCL11A_
+
CTTT
112
TTTTTAAGCAAAAAAAA
1423
UUUUUAAGCAAAAAAAAAA

exon_1

AAAAAAAAAAAAA

AAAAAAAAAAA

BCL11A_
+
TTTA
113
AGCAAAAAAAAAAAAAA
1424
AGCAAAAAAAAAAAAAAAA

exon_1

AAAAAAAAAAAAA

AAAAAAAAAAA

BCL11A_
+
GTTC
114
AAGTGCGGACGTGACGT
1425
AAGUGCGGACGUGACGUCC

exon_1

CCCTGCGAACTTG

CUGCGAACUUG

BCL11A_
+
CTTG
115
AACGTCAGGAGTCTGGA
1426
AACGUCAGGAGUCUGGAUG

exon_1

TGGACAGAGAC

GACAGAGAC

BCL11A_
−
GTTC
116
AAGTTCGCAGGGACGTC
1427
AAGUUCGCAGGGACGUCAC

exon_1

ACGTCCGCACTTG

GUCCGCACUUG

BCL11A_
+
TTTT
117
AAGCAAAAAAAAAAAAA
1428
AAGCAAAAAAAAAAAAAAA

exon_1

AAAAAAAAAAAAA

AAAAAAAAAAA

BCL11A_
−
GTTC
118
GCAGGGACGTCACGTCC
1429
GCAGGGACGUCACGUCCGC

exon_1

GCACTTGAACTTG

ACUUGAACUUG

BCL11A_
−
TTTT
119
TATCGAGCACAAACGGA
1430
UAUCGAGCACAAACGGAAA

exon_2

AACAATGCAATGG

CAAUGCAAUGG

BCL11A_
−
TTTT
120
ATCGAGCACAAACGGAA
1431
AUCGAGCACAAACGGAAAC

exon 2

ACAATGCAATGGC

AAUGCAAUGGC

BCL11A_
−
TTTA
121
TCGAGCACAAACGGAAA
1432
UCGAGCACAAACGGAAACA

exon_2

CAATGCAATGGCA

AUGCAAUGGCA

BCL11A_
−
CTTA
122
GAAAAAGCTGTGGATAA
1433
GAAAAAGCUGUGGAUAAGC

exon_2

GCCACCTTCCCCT

CACCUUCCCCU

BCL11A_
−
GTTG
123
GCATCCAGGTCACGCCA
1434
GCAUCCAGGUCACGCCAGA

exon 2

GAGGATGACGATT

GGAUGACGAUU

BCL11A_
−
CTTC
124
ACCAATCGAGATGAAAA
1435
ACCAAUCGAGAUGAAAAAA

exon 2

AAGCATCCAATCC

GCAUCCAAUCC

BCL11A_
−
ATTG
125
TTTATCAACGTCATCTA
1436
UUUAUCAACGUCAUCUAGA

exon_2

GAGGAATTTGCCC

GGAAUUUGCCC

BCL11A_
−
GTTT
126
ATCAACGTCATCTAGAG
1437
AUCAACGUCAUCUAGAGGA

exon_2

GAATTTGCCCCAA

AUUUGCCCCAA

BCL11A_
−
TTTA
127
TCAACGTCATCTAGAGG
1438
UCAACGUCAUCUAGAGGAA

exon_2

AATTTGCCCCAAA

UUUGCCCCAAA

BCL11A_
−
ATTT
128
TTATCGAGCACAAACGG
1439
UUAUCGAGCACAAACGGAA

exon_2

AAACAATGCAATG

ACAAUGCAAUG

BCL11A_
−
CTTC
129
CCCTTCACCAATCGAGA
1440
CCCUUCACCAAUCGAGAUG

exon_2

TGAAAAAAGCATC

AAAAAAGCAUC

BCL11A_
−
CTTA
130
TTTTTATCGAGCACAAA
1441
UUUUUAUCGAGCACAAACG

exon_2

CGGAAACAATGCA

GAAACAAUGCA

BCL11A_
−
CTTG
131
AAGCCATTCTTACAGAT
1442
AAGCCAUUCUUACAGAUGA

exon_2

GATGAACCAGACC

UGAACCAGACC

BCL11A_
−
ATTG
132
GGGGACATTCTTATTTT
1443
GGGGACAUUCUUAUUUUUA

exon_2

TATCGAGCACAAA

UCGAGCACAAA

BCL11A_
−
CTTC
133
CCATTGGGGGACATTCT
1444
CCAUUGGGGGACAUUCUUA

exon 2

TATTTTTATCGAG

UUUUUAUCGAG

BCL11A_
−
GTTG
134
GGAGCTCCAGAAGGGGA
1445
GGAGCUCCAGAAGGGGAUC

exon 2

TCATGACCTCCTC

AUGACCUCCUC

BCL11A_
−
CTTA
135
CAGATGATGAACCAGAC
1446
CAGAUGAUGAACCAGACCA

exon 2

CACGGCCCGTTGG

CGGCCCGUUGG

BCL11A_
−
ATTC
136
TTACAGATGATGAACCA
1447
UUACAGAUGAUGAACCAGA

exon 2

GACCACGGCCCGT

CCACGGCCCGU

BCL11A_
−
TTTC
137
TCCAACCACAGCCGAGC
1448
UCCAACCACAGCCGAGCCU

exon 2

CTCTTGAAGCCAT

CUUGAAGCCAU

BCL11A_
−
GTTT
138
CTCCAACCACAGCCGAG
1449
CUCCAACCACAGCCGAGCC

exon_2

CCTCTTGAAGCCA

UCUUGAAGCCA

BCL11A_
−
TTTG
139
TTTCTCCAACCACAGCC
1450
UUUCUCCAACCACAGCCGA

exon 2

GAGCCTCTTGAAG

GCCUCUUGAAG

BCL11A_
−
TTTT
140
GTTTCTCCAACCACAGC
1451
GUUUCUCCAACCACAGCCG

exon_2

CGAGCCTCTTGAA

AGCCUCUUGAA

BCL11A_
−
CTTT
141
TGTTTCTCCAACCACAG
1452
UGUUUCUCCAACCACAGCC

exon_2

CCGAGCCTCTTGA

GAGCCUCUUGA

BCL11A_
−
ATTG
142
TGCTTTTGTTTCTCCAA
1453
UGCUUUUGUUUCUCCAACC

exon_2

CCACAGCCGAGCC

ACAGCCGAGCC

BCL11A_
−
ATTC
143
TTATTTTTATCGAGCAC
1454
UUAUUUUUAUCGAGCACAA

exon_2

AAACGGAAACAAT

ACGGAAACAAU

BCL11A_
−
ATTT
144
GCCCCAAACAGGAACAC
1455
GCCCCAAACAGGAACACAU

exon_2

ATAGCAGGTAAAT

AGCAGGUAAAU

BCL11A_
+
CTTT
145
TCTCCTTGCTTCTCATT
1456
UCUCCUUGCUUCUCAUUUA

exon 2

TACCTGCTATGTG

CCUGCUAUGUG

BCL11A_
+
TTTT
146
CTCCTTGCTTCTCATTT
1457
CUCCUUGCUUCUCAUUUAC

exon_2

ACCTGCTATGTGT

CUGCUAUGUGU

BCL11A_
+
TTTT
147
TCTAAGCAGAGGCTGCC
1458
UCUAAGCAGAGGCUGCCAU

exon 2

ATTGCATTGTTTC

UGCAUUGUUUC

BCL11A_
+
TTTT
148
CTAAGCAGAGGCTGCCA
1459
CUAAGCAGAGGCUGCCAUU

exon_2

TTGCATTGTTTCC

GCAUUGUUUCC

BCL11A_
+
TTTC
149
TAAGCAGAGGCTGCCAT
1460
UAAGCAGAGGCUGCCAUUG

exon 2

TGCATTGTTTCCG

CAUUGUUUCCG

BCL11A_
+
ATTG
150
CATTGTTTCCGTTTGTG
1461
CAUUGUUUCCGUUUGUGCU

exon_2

CTCGATAAAAATA

CGAUAAAAAUA

BCL11A_
+
ATTG
151
TTTCCGTTTGTGCTCGA
1462
UUUCCGUUUGUGCUCGAUA

exon 2

TAAAAATAAGAAT

AAAAUAAGAAU

BCL11A_
+
GTTT
152
CCGTTTGTGCTCGATAA
1463
CCGUUUGUGCUCGAUAAAA

exon_2

AAATAAGAATGTC

AUAAGAAUGUC

BCL11A_
+
CTTT
153
TTCTAAGCAGAGGCTGC
1464
UUCUAAGCAGAGGCUGCCA

exon_2

CATTGCATTGTTT

UUGCAUUGUUU

BCL11A_
+
TTTC
154
CGTTTGTGCTCGATAAA
1465
CGUUUGUGCUCGAUAAAAA

exon_2

AATAAGAATGTCC

UAAGAAUGUCC

BCL11A_
+
TTTG
155
TGCTCGATAAAAATAAG
1466
UGCUCGAUAAAAAUAAGAA

exon 2

AATGTCCCCCAAT

UGUCCCCCAAU

BCL11A_
+
GTTC
156
ATCTGGCACTGCCCACA
1467
AUCUGGCACUGCCCACAGG

exon_2

GGTGAGGAGGTCA

UGAGGAGGUCA

BCL11A_
+
GTTC
157
ATCATCTGTAAGAATGG
1468
AUCAUCUGUAAGAAUGGCU

exon 2

CTTCAAGAGGCTC

UCAAGAGGCUC

BCL11A_
+
CTTC
158
AAGAGGCTCGGCTGTGG
1469
AAGAGGCUCGGCUGUGGUU

exon_2

TTGGAGAAACAAA

GGAGAAACAAA

BCL11A_
+
GTTG
159
GAGAAACAAAAGCACAA
1470
GAGAAACAAAAGCACAAUU

exon 2

TTATTAGAGTGCC

AUUAGAGUGCC

BCL11A_
+
ATTA
160
TTAGAGTGCCAGAGAGG
1471
UUAGAGUGCCAGAGAGGAC

exon_2

ACAGAAAGGGGAG

AGAAAGGGGAG

BCL11A_
+
GTTT
161
GTGCTCGATAAAAATAA
1472
GUGCUCGAUAAAAAUAAGA

exon_2

GAATGTCCCCCAA

AUGUCCCCCAA

BCL11A_
+
CTTA
162
TCCACAGCTTTTTCTAA
1473
UCCACAGCUUUUUCUAAGC

exon_2

GCAGAGGCTGCCA

AGAGGCUGCCA

BCL11A_
+
ATTG
163
GTGAAGGGGAAGGTGGC
1474
GUGAAGGGGAAGGUGGCUU

exon 2

TTATCCACAGCTT

AUCCACAGCUU

BCL11A_
+
TTTC
164
ATCTCGATTGGTGAAGG
1475
AUCUCGAUUGGUGAAGGGG

exon_2

GGAAGGTGGCTTA

AAGGUGGCUUA

BCL11A_
+
TTTC
165
TCCTTGCTTCTCATTTA
1476
UCCUUGCUUCUCAUUUACC

exon_2

CCTGCTATGTGTT

UGCUAUGUGUU

BCL11A_
+
CTTG
166
CTTCTCATTTACCTGCT
1477
CUUCUCAUUUACCUGCUAU

exon 2

ATGTGTTCCTGTT

GUGUUCCUGUU

BCL11A_
+
CTTC
167
TCATTTACCTGCTATGT
1478
UCAUUUACCUGCUAUGUGU

exon 2

GTTCCTGTTTGGG

UCCUGUUUGGG

BCL11A_
+
ATTT
168
ACCTGCTATGTGTTCCT
1479
ACCUGCUAUGUGUUCCUGU

exon_2

GTTTGGGGCAAAT

UUGGGGCAAAU

BCL11A_
+
TTTA
169
CCTGCTATGTGTTCCTG
1480
CCUGCUAUGUGUUCCUGUU

exon_2

TTTGGGGCAAATT

UGGGGCAAAUU

BCL11A_
+
GTTC
170
CTGTTTGGGGCAAATTC
1481
CUGUUUGGGGCAAAUUCCU

exon_2

CTCTAGATGACGT

CUAGAUGACGU

BCL11A_
+
GTTT
171
GGGGCAAATTCCTCTAG
1482
GGGGCAAAUUCCUCUAGAU

exon 2

ATGACGTTGATAA

GACGUUGAUAA

BCL11A_
+
TTTG
172
GGGCAAATTCCTCTAGA
1483
GGGCAAAUUCCUCUAGAUG

exon_2

TGACGTTGATAAA

ACGUUGAUAAA

BCL11A_
+
ATTC
173
CTCTAGATGACGTTGAT
1484
CUCUAGAUGACGUUGAUAA

exon_2

AAACAATCGTCAT

ACAAUCGUCAU

BCL11A_
+
GTTG
174
ATAAACAATCGTCATCC
1485
AUAAACAAUCGUCAUCCUC

exon 2

TCTGGCGTGACCT

UGGCGUGACCU

BCL11A_
+
ATTG
175
GATGCTTTTTTCATCTC
1486
GAUGCUUUUUUCAUCUCGA

exon 2

GATTGGTGAAGGG

UUGGUGAAGGG

BCL11A_
+
CTTT
176
TTTCATCTCGATTGGTG
1487
UUUCAUCUCGAUUGGUGAA

exon_2

AAGGGGAAGGTGG

GGGGAAGGUGG

BCL11A_
+
TTTT
177
TTCATCTCGATTGGTGA
1488
UUCAUCUCGAUUGGUGAAG

exon_2

AGGGGAAGGTGGC

GGGAAGGUGGC

BCL11A_
+
TTTT
178
TCATCTCGATTGGTGAA
1489
UCAUCUCGAUUGGUGAAGG

exon 2

GGGGAAGGTGGCT

GGAAGGUGGCU

BCL11A_
+
TTTT
179
CATCTCGATTGGTGAAG
1490
CAUCUCGAUUGGUGAAGGG

exon_2

GGGAAGGTGGCTT

GAAGGUGGCUU

BCL11A_
−
TTTG
180
CCCCAAACAGGAACACA
1491
CCCCAAACAGGAACACAUA

exon 2

TAGCAGGTAAATG

GCAGGUAAAUG

BCL11A_
+
CTTC
181
TGGAGCTCCCAACGGGC
1492
UGGAGCUCCCAACGGGCCG

exon_2

CGTGGTCTGGTTC

UGGUCUGGUUC

BCL11A_
−
GTTG
182
TTTGTAGCTGTAGTGCT
1493
UUUGUAGCUGUAGUGCUUG

exon_3

TGATTTTGGGTTT

AUUUUGGGUUU

BCL11A_
+
TTTA
183
TCTGTGAAAGAAACCCA
1494
UCUGUGAAAGAAACCCAAA

exon_3

AAATCAAGCACTA

AUCAAGCACUA

BCL11A_
−
GTTT
184
GTAGCTGTAGTGCTTGA
1495
GUAGCUGUAGUGCUUGAUU

exon_3

TTTTGGGTTTCTT

UUGGGUUUCUU

BCL11A_
−
TTTG
185
TAGCTGTAGTGCTTGAT
1496
UAGCUGUAGUGCUUGAUUU

exon_3

TTTGGGTTTCTTT

UGGGUUUCUUU

BCL11A_
−
CTTG
186
ATTTTGGGTTTCTTTCA
1497
AUUUUGGGUUUCUUUCACA

exon_3

CAGATAAACTTCT

GAUAAACUUCU

BCL11A_
−
ATTT
187
TGGGTTTCTTTCACAGA
1498
UGGGUUUCUUUCACAGAUA

exon_3

TAAACTTCTGCAC

AACUUCUGCAC

BCL11A_
−
TTTT
188
GGGTTTCTTTCACAGAT
1499
GGGUUUCUUUCACAGAUAA

exon_3

AAACTTCTGCACT

ACUUCUGCACU

BCL11A_
−
GTTT
189
CTTTCACAGATAAACTT
1500
CUUUCACAGAUAAACUUCU

exon_3

CTGCACTGGAGGG

GCACUGGAGGG

BCL11A_
−
TTTC
190
TTTCACAGATAAACTTC
1501
UUUCACAGAUAAACUUCUG

exon_3

TGCACTGGAGGGG

CACUGGAGGGG

BCL11A_
−
CTTT
191
CACAGATAAACTTCTGC
1502
CACAGAUAAACUUCUGCAC

exon_3

ACTGGAGGGGCCT

UGGAGGGGCCU

BCL11A_
−
TTTC
192
ACAGATAAACTTCTGCA
1503
ACAGAUAAACUUCUGCACU

exon_3

CTGGAGGGGCCTC

GGAGGGGCCUC

BCL11A_
−
CTTC
193
TGCACTGGAGGGGCCTC
1504
UGCACUGGAGGGGCCUCUC

exon_3

TCCTCCCCTCGTT

CUCCCCUCGUU

BCL11A_
−
GTTC
194
TGCACATGGAGCTCTAA
1505
UGCACAUGGAGCUCUAAUC

exon_3

TCCCCACGCCTGG

CCCACGCCUGG

BCL11A_
−
ATTT
195
GTAAGTTGAGCCTTATT
1506
GUAAGUUGAGCCUUAUUUC

exon_3

TCTTCTACAAATG

UUCUACAAAUG

BCL11A_
−
TTTG
196
GGTTTCTTTCACAGATA
1507
GGUUUCUUUCACAGAUAAA

exon_3

AACTTCTGCACTG

CUUCUGCACUG

BCL11A_
−
GTTG
197
AGCCTTATTTCTTCTAC
1508
AGCCUUAUUUCUUCUACAA

exon_3

AAATGTCCATGTG

AUGUCCAUGUG

BCL11A_
−
TTTG
198
TAAGTTGAGCCTTATTT
1509
UAAGUUGAGCCUUAUUUCU

exon_3

CTTCTACAAATGT

UCUACAAAUGU

BCL11A_
+
GTTT
199
ATCTGTGAAAGAAACCC
1510
AUCUGUGAAAGAAACCCAA

exon_3

AAAATCAAGCACT

AAUCAAGCACU

BCL11A_
+
ATTA
200
GAGCTCCATGTGCAGAA
1511
GAGCUCCAUGUGCAGAACG

exon_3

CGAGGGGAGGAGA

AGGGGAGGAGA

BCL11A_
+
ATTC
201
TGCACTCATCCCAGGCG
1512
UGCACUCAUCCCAGGCGUG

exon_3

TGGGGATTAGAGC

GGGAUUAGAGC

BCL11A_
+
TTTG
202
TAGAAGAAATAAGGCTC
1513
UAGAAGAAAUAAGGCUCAA

exon_3

AACTTACAAATAC

CUUACAAAUAC

BCL11A_
+
CTTA
203
CAAATACCCTGCGGGGC
1514
CAAAUACCCUGCGGGGCAU

exon 3

ATATTCTGCACTC

AUUCUGCACUC

BCL11A_
+
ATTT
204
GTAGAAGAAATAAGGCT
1515
GUAGAAGAAAUAAGGCUCA

exon_3

CAACTTACAAATA

ACUUACAAAUA

BCL11A_
−
CTTC
205
TACAAATGTCCATGTGT
1516
UACAAAUGUCCAUGUGUAU

exon_3

ATAGAGATGAGAA

AGAGAUGAGAA

BCL11A_
−
TTTC
206
TTCTACAAATGTCCATG
1517
UUCUACAAAUGUCCAUGUG

exon_3

TGTATAGAGATGA

UAUAGAGAUGA

BCL11A_
−
ATTT
207
CTTCTACAAATGTCCAT
1518
CUUCUACAAAUGUCCAUGU

exon_3

GTGTATAGAGATG

GUAUAGAGAUG

BCL11A_
−
CTTA
208
TTTCTTCTACAAATGTC
1519
UUUCUUCUACAAAUGUCCA

exon_3

CATGTGTATAGAG

UGUGUAUAGAG

BCL11A_
+
GTTT
209
TTTAAAAAAAATTTTTC
1520
UUUAAAAAAAAUUUUUCUU

exon_4

TTAACATTTATAT

AACAUUUAUAU

BCL11A_
+
TTTT
210
AAAAAAAATTTTTCTTA
1521
AAAAAAAAUUUUUCUUAAC

exon_4

ACATTTATATTTA

AUUUAUAUUUA

BCL11A_
+
TTTT
211
TAAAAAAAATTTTTCTT
1522
UAAAAAAAAUUUUUCUUAA

exon_4

AACATTTATATTT

CAUUUAUAUUU

BCL11A_
+
TTTT
212
TTAAAAAAAATTTTTCT
1523
UUAAAAAAAAUUUUUCUUA

exon_4

TAACATTTATATT

ACAUUUAUAUU

BCL11A_
+
TTTA
213
AAAAAAATTTTTCTTAA
1524
AAAAAAAUUUUUCUUAACA

exon_4

CATTTATATTTAA

UUUAUAUUUAA

BCL11A_
+
GTTC
214
CCCCCTAAACATAATGA
1525
CCCCCUAAACAUAAUGAAG

exon_4

AGTGTTTTTTAAA

UGUUUUUUAAA

BCL11A_
+
TTTC
215
CACTACCATTTTTAAAT
1526
CACUACCAUUUUUAAAUGG

exon_4

GGATAACAAGTCT

AUAACAAGUCU

BCL11A_
+
TTTA
216
AATGGATAACAAGTCTT
1527
AAUGGAUAACAAGUCUUGU

exon_4

GTAACACCACCAA

AACACCACCAA

BCL11A_
+
TTTT
217
AAATGGATAACAAGTCT
1528
AAAUGGAUAACAAGUCUUG

exon_4

TGTAACACCACCA

UAACACCACCA

BCL11A_
+
TTTT
218
TAAATGGATAACAAGTC
1529
UAAAUGGAUAACAAGUCUU

exon_4

TTGTAACACCACC

GUAACACCACC

BCL11A_
+
ATTT
219
TTAAATGGATAACAAGT
1530
UUAAAUGGAUAACAAGUCU

exon_4

CTTGTAACACCAC

UGUAACACCAC

BCL11A_
+
ATTT
220
CCACTACCATTTTTAAA
1531
CCACUACCAUUUUUAAAUG

exon_4

TGGATAACAAGTC

GAUAACAAGUC

BCL11A_
+
ATTT
221
TTCTTAACATTTATATT
1532
UUCUUAACAUUUAUAUUUA

exon_4

TAAAAAAGTTTTG

AAAAAGUUUUG

BCL11A_
+
CTTG
222
TAACACCACCAAGACAA
1533
UAACACCACCAAGACAAUG

exon 4

TGGAACCCTAAAA

GAACCCUAAAA

BCL11A_
+
TTTT
223
TCTTAACATTTATATTT
1534
UCUUAACAUUUAUAUUUAA

exon_4

AAAAAAGTTTTGT

AAAAGUUUUGU

BCL11A_
+
ATTT
224
CTATGTTAAGTGTATTC
1535
CUAUGUUAAGUGUAUUCUG

exon_4

TGTTTCCATTCAC

UUUCCAUUCAC

BCL11A_
+
TTTC
225
TTAACATTTATATTTAA
1536
UUAACAUUUAUAUUUAAAA

exon_4

AAAAGTTTTGTAC

AAGUUUUGUAC

BCL11A_
+
CTTA
226
ACATTTATATTTAAAAA
1537
ACAUUUAUAUUUAAAAAAG

exon_4

AGTTTTGTACAAA

UUUUGUACAAA

BCL11A_
+
ATTT
227
ATATTTAAAAAAGTTTT
1538
AUAUUUAAAAAAGUUUUGU

exon_4

GTACAAAAAAATC

ACAAAAAAAUC

BCL11A_
+
TTTA
228
TATTTAAAAAAGTTTTG
1539
UAUUUAAAAAAGUUUUGUA

exon_4

TACAAAAAAATCC

CAAAAAAAUCC

BCL11A_
+
ATTT
229
AAAAAAGTTTTGTACAA
1540
AAAAAAGUUUUGUACAAAA

exon_4

AAAAATCCTTGCA

AAAUCCUUGCA

BCL11A_
+
TTTA
230
AAAAAGTTTTGTACAAA
1541
AAAAAGUUUUGUACAAAAA

exon 4

AAAATCCTTGCAC

AAUCCUUGCAC

BCL11A_
+
GTTT
231
TGTACAAAAAAATCCTT
1542
UGUACAAAAAAAUCCUUGC

exon 4

GCACTGTAGAAGC

ACUGUAGAAGC

BCL11A_
+
TTTT
232
GTACAAAAAAATCCTTG
1543
GUACAAAAAAAUCCUUGCA

exon 4

CACTGTAGAAGCG

CUGUAGAAGCG

BCL11A_
+
TTTG
233
TACAAAAAAATCCTTGC
1544
UACAAAAAAAUCCUUGCAC

exon 4

ACTGTAGAAGCGA

UGUAGAAGCGA

BCL11A_
+
CTTG
234
CACTGTAGAAGCGAAAG
1545
CACUGUAGAAGCGAAAGCA

exon_4

CAATCATTCATTT

AUCAUUCAUUU

BCL11A_
+
ATTC
235
ATTTCTATGTTAAGTGT
1546
AUUUCUAUGUUAAGUGUAU

exon_4

ATTCTGTTTCCAT

UCUGUUUCCAU

BCL11A_
+
TTTA
236
CAACCTGAAGAGCGGTG
1547
CAACCUGAAGAGCGGUGUG

exon_4

TGTATCCAAGGCA

UAUCCAAGGCA

BCL11A_
+
TTTC
237
TATGTTAAGTGTATTCT
1548
UAUGUUAAGUGUAUUCUGU

exon_4

GTTTCCATTCACA

UUCCAUUCACA

BCL11A_
+
GTTA
238
AGTGTATTCTGTTTCCA
1549
AGUGUAUUCUGUUUCCAUU

exon_4

TTCACAGCGCTTG

CACAGCGCUUG

BCL11A_
+
TTTT
239
CTTAACATTTATATTTA
1550
CUUAACAUUUAUAUUUAAA

exon_4

AAAAAGTTTTGTA

AAAGUUUUGUA

BCL11A_
+
TTTT
240
ACAACCTGAAGAGCGGT
1551
ACAACCUGAAGAGCGGUGU

exon_4

GTGTATCCAAGGC

GUAUCCAAGGC

BCL11A_
+
TTTA
241
AGTACTATATAATCTTA
1552
AGUACUAUAUAAUCUUAAA

exon_4

AACCTTTCCCCAA

CCUUUCCCCAA

BCL11A_
+
TTTT
242
TTACAACCTGAAGAGCG
1553
UUACAACCUGAAGAGCGGU

exon_4

GTGTGTATCCAAG

GUGUAUCCAAG

BCL11A_
+
TTTT
243
TCCACTACCAAAAAAGG
1554
UCCACUACCAAAAAAGGUA

exon_4

TACATTGATACCT

CAUUGAUACCU

BCL11A_
+
TTTT
244
CCACTACCAAAAAAGGT
1555
CCACUACCAAAAAAGGUAC

exon_4

ACATTGATACCTT

AUUGAUACCUU

BCL11A_
+
TTTC
245
CACTACCAAAAAAGGTA
1556
CACUACCAAAAAAGGUACA

exon_4

CATTGATACCTTT

UUGAUACCUUU

BCL11A_
+
ATTG
246
ATACCTTTTAAGAGAAC
1557
AUACCUUUUAAGAGAACAA

exon_4

AAGCAACAGTTAA

GCAACAGUUAA

BCL11A_
+
CTTT
247
TAAGAGAACAAGCAACA
1558
UAAGAGAACAAGCAACAGU

exon_4

GTTAAAAATACAA

UAAAAAUACAA

BCL11A_
+
TTTT
248
AAGAGAACAAGCAACAG
1559
AAGAGAACAAGCAACAGUU

exon_4

TTAAAAATACAAG

AAAAAUACAAG

BCL11A_
+
TTTA
249
AGAGAACAAGCAACAGT
1560
AGAGAACAAGCAACAGUUA

exon_4

TAAAAATACAAGC

AAAAUACAAGC

BCL11A_
+
GTTA
250
AAAATACAAGCTTCAAT
1561
AAAAUACAAGCUUCAAUAU

exon_4

ATAAATACTATAG

AAAUACUAUAG

BCL11A_
+
CTTC
251
AATATAAATACTATAGT
1562
AAUAUAAAUACUAUAGUGC

exon_4

GCCTAACACTAGA

CUAACACUAGA

BCL11A_
+
ATTT
252
AATTCAAATACCATTCT
1563
AAUUCAAAUACCAUUCUAG

exon_4

AGAAATACAGAAA

AAAUACAGAAA

BCL11A_
+
TTTA
253
ATTCAAATACCATTCTA
1564
AUUCAAAUACCAUUCUAGA

exon 4

GAAATACAGAAAA

AAUACAGAAAA

BCL11A_
+
ATTC
254
AAATACCATTCTAGAAA
1565
AAAUACCAUUCUAGAAAUA

exon_4

TACAGAAAAAAGA

CAGAAAAAAGA

BCL11A_
+
ATTC
255
TAGAAATACAGAAAAAA
1566
UAGAAAUACAGAAAAAAGA

exon_4

GACCATAAATGTA

CCAUAAAUGUA

BCL11A_
+
ATTT
256
TAGCATAGGAATCAACA
1567
UAGCAUAGGAAUCAACAUG

exon_4

TGAGTGTGCATTT

AGUGUGCAUUU

BCL11A_
+
TTTT
257
AGCATAGGAATCAACAT
1568
AGCAUAGGAAUCAACAUGA

exon_4

GAGTGTGCATTTT

GUGUGCAUUUU

BCL11A_
+
TTTA
258
GCATAGGAATCAACATG
1569
GCAUAGGAAUCAACAUGAG

exon_4

AGTGTGCATTTTC

UGUGCAUUUUC

BCL11A_
+
ATTT
259
TCCTATATTTAAGTACT
1570
UCCUAUAUUUAAGUACUAU

exon_4

ATATAATCTTAAA

AUAAUCUUAAA

BCL11A_
+
TTTT
260
TTTACAACCTGAAGAGC
1571
UUUACAACCUGAAGAGCGG

exon_4

GGTGTGTATCCAA

UGUGUAUCCAA

BCL11A_
+
TTTT
261
TTTTACAACCTGAAGAG
1572
UUUUACAACCUGAAGAGCG

exon 4

CGGTGTGTATCCA

GUGUGUAUCCA

BCL11A_
+
TTTT
262
TTTTTACAACCTGAAGA
1573
UUUUUACAACCUGAAGAGC

exon_4

GCGGTGTGTATCC

GGUGUGUAUCC

BCL11A_
+
TTTT
263
TTTTTTACAACCTGAAG
1574
UUUUUUACAACCUGAAGAG

exon_4

AGCGGTGTGTATC

CGGUGUGUAUC

BCL11A_
+
TTTT
264
TTTTTTTACAACCTGAA
1575
UUUUUUUACAACCUGAAGA

exon_4

GAGCGGTGTGTAT

GCGGUGUGUAU

BCL11A_
+
TTTT
265
TTTTTTTTACAACCTGA
1576
UUUUUUUUACAACCUGAAG

exon_4

AGAGCGGTGTGTA

AGCGGUGUGUA

BCL11A_
+
TTTT
266
TACAACCTGAAGAGCGG
1577
UACAACCUGAAGAGCGGUG

exon_4

TGTGTATCCAAGG

UGUAUCCAAGG

BCL11A_
+
GTTT
267
TTTTTTTTTACAACCTG
1578
UUUUUUUUUACAACCUGAA

exon_4

AAGAGCGGTGTGT

GAGCGGUGUGU

BCL11A_
+
CTTT
268
CCCCAATGTATGTTTTT
1579
CCCCAAUGUAUGUUUUUUU

exon_4

TTTTTTTACAACC

UUUUUACAACC

BCL11A_
+
CTTA
269
AACCTTTCCCCAATGTA
1580
AACCUUUCCCCAAUGUAUG

exon_4

TGTTTTTTTTTTT

UUUUUUUUUUU

BCL11A_
+
ATTC
270
TGTTTCCATTCACAGCG
1581
UGUUUCCAUUCACAGCGCU

exon_4

CTTGCAATGTTGC

UGCAAUGUUGC

BCL11A_
+
ATTT
271
AAGTACTATATAATCTT
1582
AAGUACUAUAUAAUCUUAA

exon_4

AAACCTTTCCCCA

ACCUUUCCCCA

BCL11A_
+
TTTC
272
CTATATTTAAGTACTAT
1583
CUAUAUUUAAGUACUAUAU

exon_4

ATAATCTTAAACC

AAUCUUAAACC

BCL11A_
+
TTTT
273
CCTATATTTAAGTACTA
1584
CCUAUAUUUAAGUACUAUA

exon_4

TATAATCTTAAAC

UAAUCUUAAAC

BCL11A_
+
TTTC
274
CCCAATGTATGTTTTTT
1585
CCCAAUGUAUGUUUUUUUU

exon_4

TTTTTTACAACCT

UUUUACAACCU

BCL11A_
+
GTTT
275
CCATTCACAGCGCTTGC
1586
CCAUUCACAGCGCUUGCAA

exon_4

AATGTTGCGTCCA

UGUUGCGUCCA

BCL11A_
+
TTTT
276
TTAGTTTTTAAAAAATG
1587
UUAGUUUUUAAAAAAUGCU

exon_4

CTCCTCAATGAGA

CCUCAAUGAGA

BCL11A_
+
ATTC
277
ACAGCGCTTGCAATGTT
1588
ACAGCGCUUGCAAUGUUGC

exon_4

GCGTCCAAGTAAG

GUCCAAGUAAG

BCL11A_
+
ATTG
278
TCCTATCTGAGCAGGTT
1589
UCCUAUCUGAGCAGGUUUA

exon_4

TATTTTATACTCA

UUUUAUACUCA

BCL11A_
+
GTTT
279
ATTTTATACTCAACCTC
1590
AUUUUAUACUCAACCUCUG

exon_4

TGTATCTCTGATT

UAUCUCUGAUU

BCL11A_
+
TTTA
280
TTTTATACTCAACCTCT
1591
UUUUAUACUCAACCUCUGU

exon 4

GTATCTCTGATTA

AUCUCUGAUUA

BCL11A_
+
ATTT
281
TATACTCAACCTCTGTA
1592
UAUACUCAACCUCUGUAUC

exon_4

TCTCTGATTAGAG

UCUGAUUAGAG

BCL11A_
+
TTTT
282
ATACTCAACCTCTGTAT
1593
AUACUCAACCUCUGUAUCU

exon 4

CTCTGATTAGAGA

CUGAUUAGAGA

BCL11A_
+
TTTA
283
TACTCAACCTCTGTATC
1594
UACUCAACCUCUGUAUCUC

exon_4

TCTGATTAGAGAA

UGAUUAGAGAA

BCL11A_
+
ATTA
284
GAGAAAAGATACAGATA
1595
GAGAAAAGAUACAGAUAUC

exon_4

TCACAGGCAGAGT

ACAGGCAGAGU

BCL11A_
+
ATTT
285
GAACACCAACTGGGGCA
1596
GAACACCAACUGGGGCAGA

exon 4

GATGCTAGCTTAA

UGCUAGCUUAA

BCL11A_
+
TTTG
286
AACACCAACTGGGGCAG
1597
AACACCAACUGGGGCAGAU

exon_4

ATGCTAGCTTAAT

GCUAGCUUAAU

BCL11A_
+
CTTA
287
ATAAAAAAGAAAAAATT
1598
AUAAAAAAGAAAAAAUUAA

exon_4

AAAAAAATAAAAA

AAAAAUAAAAA

BCL11A_
+
ATTA
288
AAAAAATAAAAATAAAA
1599
AAAAAAUAAAAAUAAAAAC

exon 4

ACAATGAATCCTC

AAUGAAUCCUC

BCL11A_
+
CTTC
289
CATGTTAACACAAATAG
1600
CAUGUUAACACAAAUAGCA

exon 4

CACACAGTGTATG

CACAGUGUAUG

BCL11A_
+
GTTA
290
ACACAAATAGCACACAG
1601
ACACAAAUAGCACACAGUG

exon 4

TGTATGGAAAAGA

UAUGGAAAAGA

BCL11A_
+
CTTT
291
TAGGGAGCACAGACATA
1602
UAGGGAGCACAGACAUAUA

exon_4

TATACTGCTACTC

UACUGCUACUC

BCL11A_
+
TTTT
292
AGGGAGCACAGACATAT
1603
AGGGAGCACAGACAUAUAU

exon_4

ATACTGCTACTCT

ACUGCUACUCU

BCL11A_
+
TTTA
293
GGGAGCACAGACATATA
1604
GGGAGCACAGACAUAUAUA

exon_4

TACTGCTACTCTT

CUGCUACUCUU

BCL11A_
+
CTTA
294
AAATTCTTTCTCTTCTT
1605
AAAUUCUUUCUCUUCUUUU

exon_4

TTTTTAAGAATGT

UUUAAGAAUGU

BCL11A_
+
ATTC
295
ATAGTTAATCATCATTG
1606
AUAGUUAAUCAUCAUUGUA

exon_4

TATCAATATTAGC

UCAAUAUUAGC

BCL11A_
+
CTTA
296
AGAATTCATAGTTAATC
1607
AGAAUUCAUAGUUAAUCAU

exon_4

ATCATTGTATCAA

CAUUGUAUCAA

BCL11A_
+
TTTA
297
AATGCAAGTCTTAAGAA
1608
AAUGCAAGUCUUAAGAAUU

exon 4

TTCATAGTTAATC

CAUAGUUAAUC

BCL11A_
+
ATTT
298
AAATGCAAGTCTTAAGA
1609
AAAUGCAAGUCUUAAGAAU

exon 4

ATTCATAGTTAAT

UCAUAGUUAAU

BCL11A_
+
TTTA
299
AGAATGTCACATTTAAA
1610
AGAAUGUCACAUUUAAAUG

exon 4

TGCAAGTCTTAAG

CAAGUCUUAAG

BCL11A_
+
TTTT
300
AAGAATGTCACATTTAA
1611
AAGAAUGUCACAUUUAAAU

exon 4

ATGCAAGTCTTAA

GCAAGUCUUAA

BCL11A_
+
CTTA
301
ATTGTCCTATCTGAGCA
1612
AUUGUCCUAUCUGAGCAGG

exon 4

GGTTTATTTTATA

UUUAUUUUAUA

BCL11A_
+
TTTT
302
TAAGAATGTCACATTTA
1613
UAAGAAUGUCACAUUUAAA

exon_4

AATGCAAGTCTTA

UGCAAGUCUUA

BCL11A_
+
TTTT
303
TTTAAGAATGTCACATT
1614
UUUAAGAAUGUCACAUUUA

exon_4

TAAATGCAAGTCT

AAUGCAAGUCU

BCL11A_
+
CTTT
304
TTTTAAGAATGTCACAT
1615
UUUUAAGAAUGUCACAUUU

exon 4

TTAAATGCAAGTC

AAAUGCAAGUC

BCL11A_
+
CTTC
305
TTTTTTTAAGAATGTCA
1616
UUUUUUUAAGAAUGUCACA

exon 4

CATTTAAATGCAA

UUUAAAUGCAA

BCL11A_
+
TTTC
306
TCTTCTTTTTTTAAGAA
1617
UCUUCUUUUUUUAAGAAUG

exon_4

TGTCACATTTAAA

UCACAUUUAAA

BCL11A_
+
CTTT
307
CTCTTCTTTTTTTAAGA
1618
CUCUUCUUUUUUUAAGAAU

exon_4

ATGTCACATTTAA

GUCACAUUUAA

BCL11A_
+
ATTC
308
TTTCTCTTCTTTTTTTA
1619
UUUCUCUUCUUUUUUUAAG

exon_4

AGAATGTCACATT

AAUGUCACAUU

BCL11A_
+
TTTT
309
TTAAGAATGTCACATTT
1620
UUAAGAAUGUCACAUUUAA

exon_4

AAATGCAAGTCTT

AUGCAAGUCUU

BCL11A_
+
TTTC
310
CATTCACAGCGCTTGCA
1621
CAUUCACAGCGCUUGCAAU

exon_4

ATGTTGCGTCCAA

GUUGCGUCCAA

BCL11A_
+
ATTG
311
TACAGTGCACTTAATTG
1622
UACAGUGCACUUAAUUGUC

exon_4

TCCTATCTGAGCA

CUAUCUGAGCA

BCL11A_
+
TTTC
312
CCTTAAGTATAGACCTG
1623
CCUUAAGUAUAGACCUGUA

exon_4

TAAACTGGGAAAA

AACUGGGAAAA

BCL11A_
+
CTTG
313
CAATGTTGCGTCCAAGT
1624
CAAUGUUGCGUCCAAGUAA

exon_4

AAGTAAGCTCAAT

GUAAGCUCAAU

BCL11A_
+
GTTG
314
CGTCCAAGTAAGTAAGC
1625
CGUCCAAGUAAGUAAGCUC

exon_4

TCAATAGTCAAGT

AAUAGUCAAGU

BCL11A_
+
GTTT
315
TTTTTTTTTTAGTTTTT
1626
UUUUUUUUUUAGUUUUUAA

exon_4

AAAAAATGCTCCT

AAAAUGCUCCU

BCL11A_
+
TTTT
316
TTTTTTTTTAGTTTTTA
1627
UUUUUUUUUAGUUUUUAAA

exon_4

AAAAATGCTCCTC

AAAUGCUCCUC

BCL11A_
+
TTTT
317
TTTTTTTTAGTTTTTAA
1628
UUUUUUUUAGUUUUUAAAA

exon_4

AAAATGCTCCTCA

AAUGCUCCUCA

BCL11A_
+
TTTT
318
TTTTTTTAGTTTTTAAA
1629
UUUUUUUAGUUUUUAAAAA

exon_4

AAATGCTCCTCAA

AUGCUCCUCAA

BCL11A_
+
TTTT
319
TTTTTTAGTTTTTAAAA
1630
UUUUUUAGUUUUUAAAAAA

exon 4

AATGCTCCTCAAT

UGCUCCUCAAU

BCL11A_
+
TTTT
320
TTTTTAGTTTTTAAAAA
1631
UUUUUAGUUUUUAAAAAAU

exon_4

ATGCTCCTCAATG

GCUCCUCAAUG

BCL11A_
+
TTTT
321
TTTTAGTTTTTAAAAAA
1632
UUUUAGUUUUUAAAAAAUG

exon_4

TGCTCCTCAATGA

CUCCUCAAUGA

BCL11A_
+
TTTT
322
TTTAGTTTTTAAAAAAT
1633
UUUAGUUUUUAAAAAAUGC

exon_4

GCTCCTCAATGAG

UCCUCAAUGAG

BCL11A_
+
TTTT
323
TTCCACTACCAAAAAAG
1634
UUCCACUACCAAAAAAGGU

exon 4

GTACATTGATACC

ACAUUGAUACC

BCL11A_
+
TTTT
324
TAGTTTTTAAAAAATGC
1635
UAGUUUUUAAAAAAUGCUC

exon_4

TCCTCAATGAGAT

CUCAAUGAGAU

BCL11A_
+
TTTT
325
AGTTTTTAAAAAATGCT
1636
AGUUUUUAAAAAAUGCUCC

exon 4

CCTCAATGAGATT

UCAAUGAGAUU

BCL11A_
+
TTTA
326
GTTTTTAAAAAATGCTC
1637
GUUUUUAAAAAAUGCUCCU

exon_4

CTCAATGAGATTG

CAAUGAGAUUG

BCL11A_
+
GTTT
327
TTAAAAAATGCTCCTCA
1638
UUAAAAAAUGCUCCUCAAU

exon_4

ATGAGATTGTGTT

GAGAUUGUGUU

BCL11A_
+
TTTT
328
TAAAAAATGCTCCTCAA
1639
UAAAAAAUGCUCCUCAAUG

exon 4

TGAGATTGTGTTC

AGAUUGUGUUC

BCL11A_
+
TTTT
329
AAAAAATGCTCCTCAAT
1640
AAAAAAUGCUCCUCAAUGA

exon 4

GAGATTGTGTTCA

GAUUGUGUUCA

BCL11A_
+
TTTT
330
CCCTTAAGTATAGACCT
1641
CCCUUAAGUAUAGACCUGU

exon 4

GTAAACTGGGAAA

AAACUGGGAAA

BCL11A_
+
CTTT
331
TCCCTTAAGTATAGACC
1642
UCCCUUAAGUAUAGACCUG

exon 4

TGTAAACTGGGAA

UAAACUGGGAA

BCL11A_
+
CTTG
332
CAACTTTTCCCTTAAGT
1643
CAACUUUUCCCUUAAGUAU

exon 4

ATAGACCTGTAAA

AGACCUGUAAA

BCL11A_
+
ATTC
333
TTGCAACTTTTCCCTTA
1644
UUGCAACUUUUCCCUUAAG

exon 4

AGTATAGACCTGT

UAUAGACCUGU

BCL11A_
+
TTTC
334
AGCATTCTTGCAACTTT
1645
AGCAUUCUUGCAACUUUUC

exon_4

TCCCTTAAGTATA

CCUUAAGUAUA

BCL11A_
+
TTTT
335
CAGCATTCTTGCAACTT
1646
CAGCAUUCUUGCAACUUUU

exon_4

TTCCCTTAAGTAT

CCCUUAAGUAU

BCL11A_
+
CTTA
336
AGTATAGACCTGTAAAC
1647
AGUAUAGACCUGUAAACUG

exon_4

TGGGAAAATTGTA

GGAAAAUUGUA

BCL11A_
+
TTTT
337
TCAGCATTCTTGCAACT
1648
UCAGCAUUCUUGCAACUUU

exon_4

TTTCCCTTAAGTA

UCCCUUAAGUA

BCL11A_
+
TTTT
338
TTTCAGCATTCTTGCAA
1649
UUUCAGCAUUCUUGCAACU

exon_4

CTTTTCCCTTAAG

UUUCCCUUAAG

BCL11A_
+
TTTT
339
TTTTCAGCATTCTTGCA
1650
UUUUCAGCAUUCUUGCAAC

exon 4

ACTTTTCCCTTAA

UUUUCCCUUAA

BCL11A_
+
ATTT
340
TTTTTCAGCATTCTTGC
1651
UUUUUCAGCAUUCUUGCAA

exon_4

AACTTTTCCCTTA

CUUUUCCCUUA

BCL11A_
+
GTTC
341
AATTTTTTTTCAGCATT
1652
AAUUUUUUUUCAGCAUUCU

exon_4

CTTGCAACTTTTC

UGCAACUUUUC

BCL11A_
+
ATTG
342
TGTTCAATTTTTTTTCA
1653
UGUUCAAUUUUUUUUCAGC

exon_4

GCATTCTTGCAAC

AUUCUUGCAAC

BCL11A_
+
TTTA
343
AAAAATGCTCCTCAATG
1654
AAAAAUGCUCCUCAAUGAG

exon_4

AGATTGTGTTCAA

AUUGUGUUCAA

BCL11A_
+
TTTT
344
TTCAGCATTCTTGCAAC
1655
UUCAGCAUUCUUGCAACUU

exon 4

TTTTCCCTTAAGT

UUCCCUUAAGU

BCL11A_
+
TTTT
345
TTTCCACTACCAAAAAA
1656
UUUCCACUACCAAAAAAGG

exon 4

GGTACATTGATAC

UACAUUGAUAC

BCL11A_
+
TTTC
346
CAATAGAACTTAACAAA
1657
CAAUAGAACUUAACAAAGA

exon 4

GACCAGAAACAAA

CCAGAAACAAA

BCL11A_
+
TTTT
347
TTTTTCCACTACCAAAA
1658
UUUUUCCACUACCAAAAAA

exon 4

AAGGTACATTGAT

GGUACAUUGAU

BCL11A_
+
GTTT
348
TTCCAATAGAACTTAAC
1659
UUCCAAUAGAACUUAACAA

exon 4

AAAGACCAGAAAC

AGACCAGAAAC

BCL11A_
+
TTTT
349
TCCAATAGAACTTAACA
1660
UCCAAUAGAACUUAACAAA

exon_4

AAGACCAGAAACA

GACCAGAAACA

BCL11A_
+
TTTT
350
CCAATAGAACTTAACAA
1661
CCAAUAGAACUUAACAAAG

exon_4

AGACCAGAAACAA

ACCAGAAACAA

BCL11A_
+
GTTA
351
ATCATCATTGTATCAAT
1662
AUCAUCAUUGUAUCAAUAU

exon_4

ATTAGCTTATATA

UAGCUUAUAUA

BCL11A_
+
CTTA
352
ACAAAGACCAGAAACAA
1663
ACAAAGACCAGAAACAAAU

exon_4

ATACAATAAAAAG

ACAAUAAAAAG

BCL11A_
+
GTTG
353
TAATGACCTTTGGTCAT
1664
UAAUGACCUUUGGUCAUCU

exon_4

CTAAATAAAAAAA

AAAUAAAAAAA

BCL11A_
+
CTTT
354
GGTCATCTAAATAAAAA
1665
GGUCAUCUAAAUAAAAAAA

exon_4

AAAAAATAAAAAC

AAAAUAAAAAC

BCL11A_
+
TTTG
355
GTCATCTAAATAAAAAA
1666
GUCAUCUAAAUAAAAAAAA

exon_4

AAAAATAAAAACA

AAAAAAAACA

BCL11A_
+
ATTA
356
AGTGCCTCTGTTTTGAA
1667
AGUGCCUCUGUUUUGAACA

exon_4

CAGGGCACATAAG

GGGCACAUAAG

BCL11A_
+
GTTT
357
TGAACAGGGCACATAAG
1668
UGAACAGGGCACAUAAGCA

exon_4

CAATAATAAATAG

AUAAUAAAUAG

BCL11A_
+
TTTT
358
GAACAGGGCACATAAGC
1669
GAACAGGGCACAUAAGCAA

exon 4

AATAATAAATAGT

UAAUAAAUAGU

BCL11A_
+
TTTG
359
AACAGGGCACATAAGCA
1670
AACAGGGCACAUAAGCAAU

exon_4

ATAATAAATAGTG

AAUAAAUAGUG

BCL11A_
+
ATTT
360
CAAGTTACGACAAACAG
1671
CAAGUUACGACAAACAGCU

exon_4

CTTTCATTACAGG

UUCAUUACAGG

BCL11A_
+
TTTC
361
AAGTTACGACAAACAGC
1672
AAGUUACGACAAACAGCUU

exon_4

TTTCATTACAGGA

UCAUUACAGGA

BCL11A_
+
GTTA
362
ATGCAGACAACTGCCAA
1673
AUGCAGACAACUGCCAAAA

exon_4

AAAAACACAGACA

AAACACAGACA

BCL11A_
+
GTTA
363
CGACAAACAGCTTTCAT
1674
CGACAAACAGCUUUCAUUA

exon_4

TACAGGAATAGAA

CAGGAAUAGAA

BCL11A_
+
TTTC
364
ATTACAGGAATAGAAAA
1675
AUUACAGGAAUAGAAAAGG

exon_4

GGCCAATAACAAA

CCAAUAACAAA

BCL11A_
+
ATTA
365
CAGGAATAGAAAAGGCC
1676
CAGGAAUAGAAAAGGCCAA

exon_4

AATAACAAAATAT

UAACAAAAUAU

BCL11A_
+
ATTC
366
TGCATTGCCATTTACAA
1677
UGCAUUGCCAUUUACAAAA

exon 4

AAAAGTATTGACT

AAGUAUUGACU

BCL11A_
+
ATTG
367
CCATTTACAAAAAAGTA
1678
CCAUUUACAAAAAAGUAUU

exon 4

TTGACTAAAGCGG

GACUAAAGCGG

BCL11A_
+
ATTT
368
ACAAAAAAGTATTGACT
1679
ACAAAAAAGUAUUGACUAA

exon_4

AAAGCGGGCTTTC

AGCGGGCUUUC

BCL11A_
+
TTTA
369
CAAAAAAGTATTGACTA
1680
CAAAAAAGUAUUGACUAAA

exon_4

AAGCGGGCTTTCT

GCGGGCUUUCU

BCL11A_
+
ATTG
370
ACTAAAGCGGGCTTTCT
1681
ACUAAAGCGGGCUUUCUCU

exon 4

CTTTAATATGCTT

UUAAUAUGCUU

BCL11A_
+
CTTT
371
CTCTTTAATATGCTTTG
1682
CUCUUUAAUAUGCUUUGCA

exon_4

CATATGAAATTCT

UAUGAAAUUCU

BCL11A_
+
TTTC
372
TCTTTAATATGCTTTGC
1683
UCUUUAAUAUGCUUUGCAU

exon_4

ATATGAAATTCTT

AUGAAAUUCUU

BCL11A_
+
CTTT
373
AATATGCTTTGCATATG
1684
AAUAUGCUUUGCAUAUGAA

exon_4

AAATTCTTTCCAA

AUUCUUUCCAA

BCL11A_
+
TTTA
374
ATATGCTTTGCATATGA
1685
AUAUGCUUUGCAUAUGAAA

exon 4

AATTCTTTCCAAT

UUCUUUCCAAU

BCL11A_
+
CTTT
375
GCATATGAAATTCTTTC
1686
GCAUAUGAAAUUCUUUCCA

exon_4

CAATCTAAATATA

AUCUAAAUAUA

BCL11A_
+
TTTG
376
CATATGAAATTCTTTCC
1687
CAUAUGAAAUUCUUUCCAA

exon_4

AATCTAAATATAA

UCUAAAUAUAA

BCL11A_
+
ATTC
377
TTTCCAATCTAAATATA
1688
UUUCCAAUCUAAAUAUAAA

exon 4

AAGCACCATTTAG

GCACCAUUUAG

BCL11A_
+
CTTT
378
CATTACAGGAATAGAAA
1689
CAUUACAGGAAUAGAAAAG

exon_4

AGGCCAATAACAA

GCCAAUAACAA

BCL11A_
+
TTTC
379
AATAAAGGGACAAAATG
1690
AAUAAAGGGACAAAAUGGG

exon_4

GGTGTATGAACAG

UGUAUGAACAG

BCL11A_
+
TTTT
380
CAATAAAGGGACAAAAT
1691
CAAUAAAGGGACAAAAUGG

exon_4

GGGTGTATGAACA

GUGUAUGAACA

BCL11A_
+
TTTT
381
TCAATAAAGGGACAAAA
1692
UCAAUAAAGGGACAAAAUG

exon_4

TGGGTGTATGAAC

GGUGUAUGAAC

BCL11A_
−
TTTT
382
GGCAGTTGTCTGCATTA
1693
GGCAGUUGUCUGCAUUAAC

exon_4

ACCTGTTCATACA

CUGUUCAUACA

BCL11A_
−
TTTG
383
GCAGTTGTCTGCATTAA
1694
GCAGUUGUCUGCAUUAACC

exon 4

CCTGTTCATACAC

UGUUCAUACAC

BCL11A_
−
GTTG
384
TCTGCATTAACCTGTTC
1695
UCUGCAUUAACCUGUUCAU

exon 4

ATACACCCATTTT

ACACCCAUUUU

BCL11A_
−
ATTA
385
ACCTGTTCATACACCCA
1696
ACCUGUUCAUACACCCAUU

exon 4

TTTTGTCCCTTTA

UUGUCCCUUUA

BCL11A_
−
GTTC
386
ATACACCCATTTTGTCC
1697
AUACACCCAUUUUGUCCCU

exon 4

CTTTATTGAAAAA

UUAUUGAAAAA

BCL11A_
−
ATTT
387
TGTCCCTTTATTGAAAA
1698
UGUCCCUUUAUUGAAAAAA

exon 4

AATAAAAAAAATT

UAAAAAAAAUU

BCL11A_
−
TTTT
388
GTCCCTTTATTGAAAAA
1699
GUCCCUUUAUUGAAAAAAU

exon 4

ATAAAAAAAATTA

AAAAAAAAUUA

BCL11A_
−
TTTG
389
TCCCTTTATTGAAAAAA
1700
UCCCUUUAUUGAAAAAAUA

exon_4

TAAAAAAAATTAA

AAAAAAAUUAA

BCL11A_
−
CTTT
390
ATTGAAAAAATAAAAAA
1701
AUUGAAAAAAUAAAAAAAA

exon_4

AATTAAAGTACAC

UUAAAGUACAC

BCL11A_
−
TTTA
391
TTGAAAAAATAAAAAAA
1702
UUGAAAAAAUAAAAAAAAU

exon_4

ATTAAAGTACACA

UAAAGUACACA

BCL11A_
−
ATTG
392
AAAAAATAAAAAAAATT
1703
AAAAAAUAAAAAAAAUUAA

exon_4

AAAGTACACATTG

AGUACACAUUG

BCL11A_
−
ATTA
393
AAGTACACATTGTAAGC
1704
AAGUACACAUUGUAAGCUU

exon_4

TTCTTGTGTCCTC

CUUGUGUCCUC

BCL11A_
−
ATTG
394
TAAGCTTCTTGTGTCCT
1705
UAAGCUUCUUGUGUCCUCA

exon_4

CATTTGACACACT

UUUGACACACU

BCL11A_
−
CTTC
395
TTGTGTCCTCATTTGAC
1706
UUGUGUCCUCAUUUGACAC

exon_4

ACACTCTGTAAAT

ACUCUGUAAAU

BCL11A_
−
CTTG
396
TGTCCTCATTTGACACA
1707
UGUCCUCAUUUGACACACU

exon_4

CTCTGTAAATTAC

CUGUAAAUUAC

BCL11A_
−
ATTT
397
GACACACTCTGTAAATT
1708
GACACACUCUGUAAAUUAC

exon_4

ACTTGCAAGAAAA

UUGCAAGAAAA

BCL11A_
−
TTTG
398
ACACACTCTGTAAATTA
1709
ACACACUCUGUAAAUUACU

exon_4

CTTGCAAGAAAAT

UGCAAGAAAAU

BCL11A_
+
TTTT
399
TTCAATAAAGGGACAAA
1710
UUCAAUAAAGGGACAAAAU

exon_4

ATGGGTGTATGAA

GGGUGUAUGAA

BCL11A_
+
ATTT
400
TTTCAATAAAGGGACAA
1711
UUUCAAUAAAGGGACAAAA

exon_4

AATGGGTGTATGA

UGGGUGUAUGA

BCL11A_
+
TTTA
401
TTTTTTCAATAAAGGGA
1712
UUUUUUCAAUAAAGGGACA

exon_4

CAAAATGGGTGTA

AAAUGGGUGUA

BCL11A_
+
TTTT
402
ATTTTTTCAATAAAGGG
1713
AUUUUUUCAAUAAAGGGAC

exon_4

ACAAAATGGGTGT

AAAAUGGGUGU

BCL11A_
+
TTTT
403
TATTTTTTCAATAAAGG
1714
UAUUUUUUCAAUAAAGGGA

exon_4

GACAAAATGGGTG

CAAAAUGGGUG

BCL11A_
+
TTTT
404
TTATTTTTTCAATAAAG
1715
UUAUUUUUUCAAUAAAGGG

exon 4

GGACAAAATGGGT

ACAAAAUGGGU

BCL11A_
+
CTTT
405
CCAATCTAAATATAAAG
1716
CCAAUCUAAAUAUAAAGCA

exon 4

CACCATTTAGTTT

CCAUUUAGUUU

BCL11A_
+
TTTT
406
TTTATTTTTTCAATAAA
1717
UUUAUUUUUUCAAUAAAGG

exon 4

GGGACAAAATGGG

GACAAAAUGGG

BCL11A_
+
ATTT
407
TTTTTATTTTTTCAATA
1718
UUUUUAUUUUUUCAAUAAA

exon_4

AAGGGACAAAATG

GGGACAAAAUG

BCL11A_
+
TTTA
408
ATTTTTTTTATTTTTTC
1719
AUUUUUUUUAUUUUUUCAA

exon_4

AATAAAGGGACAA

UAAAGGGACAA

BCL11A_
+
CTTT
409
AATTTTTTTTATTTTTT
1720
AAUUUUUUUUAUUUUUUCA

exon_4

CAATAAAGGGACA

AUAAAGGGACA

BCL11A_
+
CTTA
410
CAATGTGTACTTTAATT
1721
CAAUGUGUACUUUAAUUUU

exon_4

TTTTTTATTTTTT

UUUUAUUUUUU

BCL11A_
+
TTTA
411
CAGAGTGTGTCAAATGA
1722
CAGAGUGUGUCAAAUGAGG

exon_4

GGACACAAGAAGC

ACACAAGAAGC

BCL11A_
+
ATTT
412
ACAGAGTGTGTCAAATG
1723
ACAGAGUGUGUCAAAUGAG

exon_4

AGGACACAAGAAG

GACACAAGAAG

BCL11A_
+
TTTT
413
TTTTATTTTTTCAATAA
1724
UUUUAUUUUUUCAAUAAAG

exon_4

AGGGACAAAATGG

GGACAAAAUGG

BCL11A_
+
TTTC
414
CAATCTAAATATAAAGC
1725
CAAUCUAAAUAUAAAGCAC

exon_4

ACCATTTAGTTTT

CAUUUAGUUUU

BCL11A_
+
ATTT
415
AGTTTTTGGCAATGAAA
1726
AGUUUUUGGCAAUGAAAAA

exon_4

AAAACTGCAAAAC

AACUGCAAAAC

BCL11A_
+
TTTA
416
GTTTTTGGCAATGAAAA
1727
GUUUUUGGCAAUGAAAAAA

exon 4

AAACTGCAAAACA

ACUGCAAAACA

BCL11A_
+
ATTA
417
GCTTGCAGTACTGCATA
1728
GCUUGCAGUACUGCAUACA

exon_4

CAGTATGGCAGCA

GUAUGGCAGCA

BCL11A_
+
CTTG
418
CAGTACTGCATACAGTA
1729
CAGUACUGCAUACAGUAUG

exon_4

TGGCAGCAGGAAA

GCAGCAGGAAA

BCL11A_
+
ATTC
419
TAGCAGGCTCCCCCAAA
1730
UAGCAGGCUCCCCCAAACC

exon_4

CCGCCATTATATG

GCCAUUAUAUG

BCL11A_
+
ATTA
420
TATGGCTTCTCATCTGT
1731
UAUGGCUUCUCAUCUGUAA

exon_4

AATGTCACACTTT

UGUCACACUUU

BCL11A_
+
CTTC
421
TCATCTGTAATGTCACA
1732
UCAUCUGUAAUGUCACACU

exon_4

CTTTTTTGTTTCT

UUUUUGUUUCU

BCL11A_
+
CTTT
422
TTTGTTTCTCTCTTTTT
1733
UUUGUUUCUCUCUUUUUUU

exon_4

TTTTTTTTTGAAG

UUUUUUUGAAG

BCL11A_
+
TTTT
423
TTGTTTCTCTCTTTTTT
1734
UUGUUUCUCUCUUUUUUUU

exon_4

TTTTTTTTGAAGC

UUUUUUGAAGC

BCL11A_
+
TTTT
424
TGTTTCTCTCTTTTTTT
1735
UGUUUCUCUCUUUUUUUUU

exon 4

TTTTTTTGAAGCA

UUUUUGAAGCA

BCL11A_
+
TTTT
425
GTTTCTCTCTTTTTTTT
1736
GUUUCUCUCUUUUUUUUUU

exon_4

TTTTTTGAAGCAT

UUUUGAAGCAU

BCL11A_
+
TTTG
426
TTTCTCTCTTTTTTTTT
1737
UUUCUCUCUUUUUUUUUUU

exon_4

TTTTTGAAGCATA

UUUGAAGCAUA

BCL11A_
+
GTTT
427
CTCTCTTTTTTTTTTTT
1738
CUCUCUUUUUUUUUUUUUU

exon_4

TTGAAGCATACAA

GAAGCAUACAA

BCL11A_
+
TTTC
428
TCTCTTTTTTTTTTTTT
1739
UCUCUUUUUUUUUUUUUUG

exon_4

TGAAGCATACAAA

AAGCAUACAAA

BCL11A_
+
CTTT
429
TTTTTTTTTTTGAAGCA
1740
UUUUUUUUUUUGAAGCAUA

exon_4

TACAAATAATTTG

CAAAUAAUUUG

BCL11A_
+
TTTT
430
TTTTTTTTTTGAAGCAT
1741
UUUUUUUUUUGAAGCAUAC

exon_4

ACAAATAATTTGC

AAAUAAUUUGC

BCL11A_
+
TTTT
431
TTTTTTTTTGAAGCATA
1742
UUUUUUUUUGAAGCAUACA

exon_4

CAAATAATTTGCA

AAUAAUUUGCA

BCL11A_
+
TTTT
432
TTTTTTTTGAAGCATAC
1743
UUUUUUUUGAAGCAUACAA

exon_4

AAATAATTTGCAC

AUAAUUUGCAC

BCL11A_
+
TTTT
433
TTTTTTTGAAGCATACA
1744
UUUUUUUGAAGCAUACAAA

exon_4

AATAATTTGCACT

UAAUUUGCACU

BCL11A_
+
TTTT
434
TTTTTTCCACTACCAAA
1745
UUUUUUCCACUACCAAAAA

exon_4

AAAGGTACATTGA

AGGUACAUUGA

BCL11A_
+
CTTT
435
TTTTTTTCCACTACCAA
1746
UUUUUUUCCACUACCAAAA

exon 4

AAAAGGTACATTG

AAGGUACAUUG

BCL11A_
+
ATTA
436
AAAAAATATACTGTGGC
1747
AAAAAAUAUACUGUGGCAG

exon_4

AGCCTGTCTTTTT

CCUGUCUUUUU

BCL11A_
+
ATTA
437
TCCTGCCAAATTAAAAA
1748
UCCUGCCAAAUUAAAAAAA

exon 4

AATATACTGTGGC

UAUACUGUGGC

BCL11A_
+
TTTG
438
CACTATATTATCCTGCC
1749
CACUAUAUUAUCCUGCCAA

exon 4

AAATTAAAAAAAT

AUUAAAAAAAU

BCL11A_
+
ATTT
439
GCACTATATTATCCTGC
1750
GCACUAUAUUAUCCUGCCA

exon 4

CAAATTAAAAAAA

AAUUAAAAAAA

BCL11A_
+
GTTA
440
TTAGCTTGCAGTACTGC
1751
UUAGCUUGCAGUACUGCAU

exon_4

ATACAGTATGGCA

ACAGUAUGGCA

BCL11A_
+
TTTG
441
AAGCATACAAATAATTT
1752
AAGCAUACAAAUAAUUUGC

exon 4

GCACTATATTATC

ACUAUAUUAUC

BCL11A_
+
TTTT
442
TGAAGCATACAAATAAT
1753
UGAAGCAUACAAAUAAUUU

exon_4

TTGCACTATATTA

GCACUAUAUUA

BCL11A_
+
TTTT
443
TTGAAGCATACAAATAA
1754
UUGAAGCAUACAAAUAAUU

exon_4

TTTGCACTATATT

UGCACUAUAUU

BCL11A_
+
TTTT
444
TTTGAAGCATACAAATA
1755
UUUGAAGCAUACAAAUAAU

exon_4

ATTTGCACTATAT

UUGCACUAUAU

BCL11A_
+
TTTT
445
TTTTGAAGCATACAAAT
1756
UUUUGAAGCAUACAAAUAA

exon_4

AATTTGCACTATA

UUUGCACUAUA

BCL11A_
+
TTTT
446
TTTTTGAAGCATACAAA
1757
UUUUUGAAGCAUACAAAUA

exon_4

TAATTTGCACTAT

AUUUGCACUAU

BCL11A_
+
TTTT
447
TTTTTTGAAGCATACAA
1758
UUUUUUGAAGCAUACAAAU

exon_4

ATAATTTGCACTA

AAUUUGCACUA

BCL11A_
+
TTTT
448
GAAGCATACAAATAATT
1759
GAAGCAUACAAAUAAUUUG

exon_4

TGCACTATATTAT

CACUAUAUUAU

BCL11A_
+
TTTT
449
TTTTCCACTACCAAAAA
1760
UUUUCCACUACCAAAAAAG

exon_4

AGGTACATTGATA

GUACAUUGAUA

BCL11A_
+
TTTA
450
CTGCATATGAAGGTAAG
1761
CUGCAUAUGAAGGUAAGAU

exon_4

ATGCTGGAATGTA

GCUGGAAUGUA

BCL11A_
+
CTTT
451
TACTGCATATGAAGGTA
1762
UACUGCAUAUGAAGGUAAG

exon_4

AGATGCTGGAATG

AUGCUGGAAUG

BCL11A_
+
GTTT
452
TTGGCAATGAAAAAAAC
1763
UUGGCAAUGAAAAAAACUG

exon_4

TGCAAAACATTGG

CAAAACAUUGG

BCL11A_
+
TTTT
453
TGGCAATGAAAAAAACT
1764
UGGCAAUGAAAAAAACUGC

exon_4

GCAAAACATTGGT

AAAACAUUGGU

BCL11A_
+
TTTT
454
GGCAATGAAAAAAACTG
1765
GGCAAUGAAAAAAACUGCA

exon_4

CAAAACATTGGTT

AAACAUUGGUU

BCL11A_
+
TTTG
455
GCAATGAAAAAAACTGC
1766
GCAAUGAAAAAAACUGCAA

exon_4

AAAACATTGGTTT

AACAUUGGUUU

BCL11A_
+
ATTG
456
GTTTTTTTTTTTTTTTC
1767
GUUUUUUUUUUUCCUUUUU

exon_4

CTTTTTTTTTCTT

UUUUUUUUCUU

BCL11A_
+
GTTT
457
TTTTTTTTTTTTCCTTT
1768
UUUUUUUUUUUUCCUUUUU

exon_4

TTTTTTCTTTCTT

UUUUCUUUCUU

BCL11A_
+
TTTT
458
TTTTTTTTTTTCCTTTT
1769
UUUUUUUUUUUCCUUUUUU

exon_4

TTTTTCTTTCTTT

UUUCUUUCUUU

BCL11A_
+
TTTT
459
TTTTTTTTTTCCTTTTT
1770
UUUUUUUUUUCCUUUUUUU

exon_4

TTTTCTTTCTTTC

UUCUUUCUUUC

BCL11A_
+
TTTT
460
TTTTTTTTTCCTTTTTT
1771
UUUUUUUUUCCUUUUUUUU

exon_4

TTTCTTTCTTTCT

UCUUUCUUUCU

BCL11A_
+
TTTT
461
TTTTTTTTCCTTTTTTT
1772
UUUUUUUUUUUUCCUUUUU

exon_4

TTCTTTCTTTCTT

CUUUCUUUCUU

BCL11A_
+
TTTT
462
TTTTTTTCCTTTTTTTT
1773
UUUUUUUCCUUUUUUUUUC

exon_4

TCTTTCTTTCTTT

UUUCUUUCUUU

BCL11A_
+
TTTT
463
TTTTTTCCTTTTTTTTT
1774
UUUUUUCCUUUUUUUUUCU

exon_4

CTTTCTTTCTTTT

UUCUUUCUUUU

BCL11A_
+
TTTT
464
TTTTTCCTTTTTTTTTC
1775
UUUUUCCUUUUUUUUUCUU

exon 4

TTTCTTTCTTTTA

UCUUUCUUUUA

BCL11A_
+
TTTT
465
TTTTCCTTTTTTTTTCT
1776
UUUUCCUUUUUUUUUCUUU

exon_4

TTCTTTCTTTTAC

CUUUCUUUUAC

BCL11A_
+
TTTT
466
TTTCCTTTTTTTTTCTT
1777
UUUCCUUUUUUUUUCUUUC

exon_4

TCTTTCTTTTACT

UUUCUUUUACU

BCL11A_
+
TTTT
467
TTCCTTTTTTTTTCTTT
1778
UUCCUUUUUUUUUCUUUCU

exon_4

CTTTCTTTTACTG

UUCUUUUACUG

BCL11A_
+
TTTT
468
TCCTTTTTTTTTCTTTC
1779
UCCUUUUUUUUUCUUUCUU

exon_4

TTTCTTTTACTGC

UCUUUUACUGC

BCL11A_
+
TTTC
469
TTTTACTGCATATGAAG
1780
UUUUACUGCAUAUGAAGGU

exon_4

GTAAGATGCTGGA

AAGAUGCUGGA

BCL11A_
+
CTTT
470
CTTTTACTGCATATGAA
1781
CUUUUACUGCAUAUGAAGG

exon 4

GGTAAGATGCTGG

UAAGAUGCUGG

BCL11A_
+
TTTC
471
TTTCTTTTACTGCATAT
1782
UUUCUUUUACUGCAUAUGA

exon_4

GAAGGTAAGATGC

AGGUAAGAUGC

BCL11A_
+
CTTT
472
CTTTCTTTTACTGCATA
1783
CUUUCUUUUACUGCAUAUG

exon_4

TGAAGGTAAGATG

AAGGUAAGAUG

BCL11A_
+
TTTC
473
TTTCTTTCTTTTACTGC
1784
UUUCUUUCUUUUACUGCAU

exon_4

ATATGAAGGTAAG

AUGAAGGUAAG

BCL11A_
+
TTTT
474
CTTTCTTTCTTTTACTG
1785
CUUUCUUUCUUUUACUGCA

exon 4

CATATGAAGGTAA

UAUGAAGGUAA

BCL11A_
+
TTTT
475
ACTGCATATGAAGGTAA
1786
ACUGCAUAUGAAGGUAAGA

exon_4

GATGCTGGAATGT

UGCUGGAAUGU

BCL11A_
+
TTTT
476
TCTTTCTTTCTTTTACT
1787
UCUUUCUUUCUUUUACUGC

exon_4

GCATATGAAGGTA

AUAUGAAGGUA

BCL11A_
+
TTTT
477
TTTCTTTCTTTCTTTTA
1788
UUUCUUUCUUUCUUUUACU

exon_4

CTGCATATGAAGG

GCAUAUGAAGG

BCL11A_
+
TTTT
478
TTTTCTTTCTTTCTTTT
1789
UUUUCUUUCUUUCUUUUAC

exon_4

ACTGCATATGAAG

UGCAUAUGAAG

BCL11A_
+
TTTT
479
TTTTTCTTTCTTTCTTT
1790
UUUUUCUUUCUUUCUUUUA

exon_4

TACTGCATATGAA

CUGCAUAUGAA

BCL11A_
+
CTTT
480
TTTTTTCTTTCTTTCTT
1791
UUUUUUUUUCUUUCUUUU

exon_4

TTACTGCATATGA

ACUGCAUAUGA

BCL11A_
+
TTTC
481
CTTTTTTTTTCTTTCTT
1792
CUUUUUUUUUCUUUCUUUC

exon_4

TCTTTTACTGCAT

UUUUACUGCAU

BCL11A_
+
TTTT
482
CCTTTTTTTTTCTTTCT
1793
CCUUUUUUUUUCUUUCUUU

exon 4

TTCTTTTACTGCA

CUUUUACUGCA

BCL11A_
+
TTTT
483
TTCTTTCTTTCTTTTAC
1794
UUCUUUCUUUCUUUUACUG

exon 4

TGCATATGAAGGT

CAUAUGAAGGU

BCL11A_
+
ATTG
484
TATCAATATTAGCTTAT
1795
UAUCAAUAUUAGCUUAUAU

exon 4

ATACCTGTTCTAG

ACCUGUUCUAG

BCL11A_
+
ATTC
485
AAGGCCTTTTTTCTTCC
1796
AAGGCCUUUUUUCUUCCUU

exon 4

TTTCCAATTGATA

UCCAAUUGAUA

BCL11A_
+
CTTA
486
TATACCTGTTCTAGTTT
1797
UAUACCUGUUCUAGUUUUA

exon_4

TAAATGGCAAATA

AAUGGCAAAUA

BCL11A_
+
TTTC
487
ATGTGTTTCTCCAGGGT
1798
AUGUGUUUCUCCAGGGUAC

exon_4

ACTGTACACGCTA

UGUACACGCUA

BCL11A_
+
GTTT
488
CTCCAGGGTACTGTACA
1799
CUCCAGGGUACUGUACACG

exon_4

CGCTAAAAGGCAT

CUAAAAGGCAU

BCL11A_
+
TTTC
489
TCCAGGGTACTGTACAC
1800
UCCAGGGUACUGUACACGC

exon_4

GCTAAAAGGCATC

UAAAAGGCAUC

BCL11A_
+
CTTA
490
CAAATTTCACATTTGTA
1801
CAAAUUUCACAUUUGUAAA

exon_4

AACGTCCTTCCCC

CGUCCUUCCCC

BCL11A_
+
ATTT
491
CACATTTGTAAACGTCC
1802
CACAUUUGUAAACGUCCUU

exon_4

TTCCCCACCTGGC

CCCCACCUGGC

BCL11A_
+
TTTC
492
ACATTTGTAAACGTCCT
1803
ACAUUUGUAAACGUCCUUC

exon_4

TCCCCACCTGGCC

CCCACCUGGCC

BCL11A_
+
ATTT
493
GTAAACGTCCTTCCCCA
1804
GUAAACGUCCUUCCCCACC

exon 4

CCTGGCCATGCGT

UGGCCAUGCGU

BCL11A_
+
TTTG
494
TAAACGTCCTTCCCCAC
1805
UAAACGUCCUUCCCCACCU

exon_4

CTGGCCATGCGTT

GGCCAUGCGUU

BCL11A_
+
CTTC
495
CCCACCTGGCCATGCGT
1806
CCCACCUGGCCAUGCGUUU

exon 4

TTTCATGTGCCTG

UCAUGUGCCUG

BCL11A_
+
GTTT
496
TCATGTGCCTGGTGAGC
1807
UCAUGUGCCUGGUGAGCUU

exon_4

TTGCTACTCTGGG

GCUACUCUGGG

BCL11A_
+
TTTT
497
CATGTGCCTGGTGAGCT
1808
CAUGUGCCUGGUGAGCUUG

exon_4

TGCTACTCTGGGC

CUACUCUGGGC

BCL11A_
+
TTTC
498
ATGTGCCTGGTGAGCTT
1809
AUGUGCCUGGUGAGCUUGC

exon_4

GCTACTCTGGGCA

UACUCUGGGCA

BCL11A_
+
CTTG
499
CTACTCTGGGCACAGGC
1810
CUACUCUGGGCACAGGCAU

exon 4

ATAGTTGCACAGC

AGUUGCACAGC

BCL11A_
+
GTTG
500
CACAGCTCGCATTTATA
1811
CACAGCUCGCAUUUAUAAG

exon_4

AGGCCTTTCGCCC

GCCUUUCGCCC

BCL11A_
+
TTTT
501
CATGTGTTTCTCCAGGG
1812
CAUGUGUUUCUCCAGGGUA

exon_4

TACTGTACACGCT

CUGUACACGCU

BCL11A_
+
ATTT
502
ATAAGGCCTTTCGCCCG
1813
AUAAGGCCUUUCGCCCGUG

exon_4

TGTGGCTTCTCCT

UGGCUUCUCCU

BCL11A_
+
CTTT
503
CGCCCGTGTGGCTTCTC
1814
CGCCCGUGUGGCUUCUCCU

exon_4

CTGTGGACAGTGA

GUGGACAGUGA

BCL11A_
+
TTTC
504
GCCCGTGTGGCTTCTCC
1815
GCCCGUGUGGCUUCUCCUG

exon 4

TGTGGACAGTGAG

UGGACAGUGAG

BCL11A_
+
CTTC
505
TCCTGTGGACAGTGAGA
1816
UCCUGUGGACAGUGAGAUU

exon_4

TTGCTACAGTTCT

GCUACAGUUCU

BCL11A_
+
ATTG
506
CTACAGTTCTTGAAGAC
1817
CUACAGUUCUUGAAGACUU

exon_4

TTTCCCACAGTAC

UCCCACAGUAC

BCL11A_
+
GTTC
507
TTGAAGACTTTCCCACA
1818
UUGAAGACUUUCCCACAGU

exon_4

GTACTCACAAGTG

ACUCACAAGUG

BCL11A_
+
CTTG
508
AAGACTTTCCCACAGTA
1819
AAGACUUUCCCACAGUACU

exon 4

CTCACAAGTGTCG

CACAAGUGUCG

BCL11A_
+
CTTT
509
CCCACAGTACTCACAAG
1820
CCCACAGUACUCACAAGUG

exon_4

TGTCGCTGCGTCT

UCGCUGCGUCU

BCL11A_
+
TTTC
510
CCACAGTACTCACAAGT
1821
CCACAGUACUCACAAGUGU

exon_4

GTCGCTGCGTCTG

CGCUGCGUCUG

BCL11A_
+
CTTT
511
TGAGCTGGGCCTGCCCG
1822
UGAGCUGGGCCUGCCCGGG

exon_4

GGCCCGGACCACT

CCCGGACCACU

BCL11A_
+
TTTT
512
GAGCTGGGCCTGCCCGG
1823
GAGCUGGGCCUGCCCGGGC

exon_4

GCCCGGACCACTA

CCGGACCACUA

BCL11A_
+
TTTG
513
AGCTGGGCCTGCCCGGG
1824
AGCUGGGCCUGCCCGGGCC

exon 4

CCCGGACCACTAA

CGGACCACUAA

BCL11A_
+
CTTC
514
CCGTGCCGCTGCGCCCC
1825
CCGUGCCGCUGCGCCCCGA

exon 4

GAGATCCCTCCGT

GAUCCCUCCGU

BCL11A_
+
GTTC
515
TCCGAGGAGTGCTCCGA
1826
UCCGAGGAGUGCUCCGACG

exon_4

CGAGGAGGCAAAA

AGGAGGCAAAA

BCL11A_
+
ATTG
516
TCTGGAGTCTCCGAAGC
1827
UCUGGAGUCUCCGAAGCUA

exon_4

TAAGGAAGGGATC

AGGAAGGGAUC

BCL11A_
+
TTTA
517
TAAGGCCTTTCGCCCGT
1828
UAAGGCCUUUCGCCCGUGU

exon_4

GTGGCTTCTCCTG

GGCUUCUCCUG

BCL11A_
+
TTTT
518
TCATGTGTTTCTCCAGG
1829
UCAUGUGUUUCUCCAGGGU

exon_4

GTACTGTACACGC

ACUGUACACGC

BCL11A_
+
TTTT
519
TTCATGTGTTTCTCCAG
1830
UUCAUGUGUUUCUCCAGGG

exon_4

GGTACTGTACACG

UACUGUACACG

BCL11A_
+
ATTT
520
TTTCATGTGTTTCTCCA
1831
UUUCAUGUGUUUCUCCAGG

exon_4

GGGTACTGTACAC

GUACUGUACAC

BCL11A_
+
GTTT
521
AAAAAAAAACATACACA
1832
AAAAAAAAACAUACACAAC

exon_4

ACATGTAAATTAT

AUGUAAAUUAU

BCL11A_
+
TTTA
522
AAAAAAAACATACACAA
1833
AAAAAAAACAUACACAACA

exon 4

CATGTAAATTATT

UGUAAAUUAUU

BCL11A_
+
ATTA
523
TTGCACAAGAGAAAGGC
1834
UUGCACAAGAGAAAGGCUC

exon_4

TCAAAGTTTGCGT

AAAGUUUGCGU

BCL11A_
+
ATTG
524
CACAAGAGAAAGGCTCA
1835
CACAAGAGAAAGGCUCAAA

exon_4

AAGTTTGCGTAAA

GUUUGCGUAAA

BCL11A_
+
GTTT
525
GCGTAAAATGCAATAGT
1836
GCGUAAAAUGCAAUAGUAU

exon_4

ATTGCCCCATACA

UGCCCCAUACA

BCL11A_
+
TTTG
526
CGTAAAATGCAATAGTA
1837
CGUAAAAUGCAAUAGUAUU

exon_4

TTGCCCCATACAG

GCCCCAUACAG

BCL11A_
+
ATTG
527
CCCCATACAGATCATGC
1838
CCCCAUACAGAUCAUGCAU

exon 4

ATTCAAACGGTGA

UCAAACGGUGA

BCL11A_
+
ATTC
528
AAACGGTGAGAACATAA
1839
AAACGGUGAGAACAUAAAG

exon_4

AGGAAAAAAAAAA

GAAAAAAAAAA

BCL11A_
+
ATTC
529
TTAGCTTCGTTACTTCT
1840
UUAGCUUCGUUACUUCUGU

exon_4

GTTTGTTTGTTTG

UUGUUUGUUUG

BCL11A_
+
CTTA
530
GCTTCGTTACTTCTGTT
1841
GCUUCGUUACUUCUGUUUG

exon_4

TGTTTGTTTGTTT

UUUGUUUGUUU

BCL11A_
+
CTTC
531
GTTACTTCTGTTTGTTT
1842
GUUACUUCUGUUUGUUUGU

exon_4

GTTTGTTTGTTTA

UUGUUUGUUUA

BCL11A_
+
GTTA
532
CTTCTGTTTGTTTGTTT
1843
CUUCUGUUUGUUUGUUUGU

exon_4

GTTTGTTTAAATC

UUGUUUAAAUC

BCL11A_
+
CTTC
533
TGTTTGTTTGTTTGTTT
1844
UGUUUGUUUGUUUGUUUGU

exon_4

GTTTAAATCACAT

UUAAAUCACAU

BCL11A_
+
GTTT
534
GTTTGTTTGTTTGTTTA
1845
GUUUGUUUGUUUGUUUAAA

exon_4

AATCACATGGGAC

UCACAUGGGAC

BCL11A_
+
TTTG
535
TTTGTTTGTTTGTTTAA
1846
UUUGUUUGUUUGUUUAAAU

exon_4

ATCACATGGGACT

CACAUGGGACU

BCL11A_
+
GTTT
536
GTTTGTTTGTTTAAATC
1847
GUUUGUUUGUUUAAAUCAC

exon_4

ACATGGGACTAGA

AUGGGACUAGA

BCL11A_
+
TTTG
537
TTTGTTTGTTTAAATCA
1848
UUUGUUUGUUUAAAUCACA

exon_4

CATGGGACTAGAA

UGGGACUAGAA

BCL11A_
+
ATTC
538
AACACTCGATCACTGTG
1849
AACACUCGAUCACUGUGCC

exon_4

CCATTTTTTCATG

AUUUUUUCAUG

BCL11A_
+
ATTA
539
TTCAACACTCGATCACT
1850
UUCAACACUCGAUCACUGU

exon_4

GTGCCATTTTTTC

GCCAUUUUUUC

BCL11A_
+
TTTA
540
TATCATTATTCAACACT
1851
UAUCAUUAUUCAACACUCG

exon_4

CGATCACTGTGCC

AUCACUGUGCC

BCL11A_
+
TTTT
541
ATATCATTATTCAACAC
1852
AUAUCAUUAUUCAACACUC

exon 4

TCGATCACTGTGC

GAUCACUGUGC

BCL11A_
+
TTTT
542
TATATCATTATTCAACA
1853
UAUAUCAUUAUUCAACACU

exon_4

CTCGATCACTGTG

CGAUCACUGUG

BCL11A_
+
GTTT
543
TTATATCATTATTCAAC
1854
UUAUAUCAUUAUUCAACAC

exon 4

ACTCGATCACTGT

UCGAUCACUGU

BCL11A_
+
CTTT
544
GAGCTGCCTGGAGGCCG
1855
GAGCUGCCUGGAGGCCGCG

exon_4

CGTAGCCGGCGAG

UAGCCGGCGAG

BCL11A_
+
ATTC
545
AGTTTTTATATCATTAT
1856
AGUUUUUAUAUCAUUAUUC

exon_4

TCAACACTCGATC

AACACUCGAUC

BCL11A_
+
TTTA
546
AATCACATGGGACTAGA
1857
AAUCACAUGGGACUAGAAA

exon_4

AAAAAATCCTACA

AAAAUCCUACA

BCL11A_
+
GTTT
547
AAATCACATGGGACTAG
1858
AAAUCACAUGGGACUAGAA

exon_4

AAAAAAATCCTAC

AAAAAUCCUAC

BCL11A_
+
TTTG
548
TTTAAATCACATGGGAC
1859
UUUAAAUCACAUGGGACUA

exon_4

TAGAAAAAAATCC

GAAAAAAAUCC

BCL11A_
−
GTTT
549
GTTTAAATCACATGGGA
1860
GUUUAAAUCACAUGGGACU

exon_4

CTAGAAAAAAATC

AGAAAAAAAUC

BCL11A_
+
TTTG
550
TTTGTTTAAATCACATG
1861
UUUGUUUAAAUCACAUGGG

exon 4

GGACTAGAAAAAA

ACUAGAAAAAA

BCL11A_
+
GTTT
551
GTTTGTTTAAATCACAT
1862
GUUUGUUUAAAUCACAUGG

exon 4

GGGACTAGAAAAA

GACUAGAAAAA

BCL11A_
+
ATTA
552
ATATACCTCTATTCAGT
1863
AUAUACCUCUAUUCAGUUU

exon_4

TTTTATATCATTA

UUAUAUCAUUA

BCL11A_
+
TTTG
553
AGCTGCCTGGAGGCCGC
1864
AGCUGCCUGGAGGCCGCGU

exon 4

GTAGCCGGCGAGC

AGCCGGCGAGC

BCL11A_
+
GTTC
554
TCCGTGTTGGGCATCGC
1865
UCCGUGUUGGGCAUCGCGG

exon_4

GGCCGGGGGCAGG

CCGGGGGCAGG

BCL11A_
+
GTTG
555
GGCATCGCGGCCGGGGG
1866
GGCAUCGCGGCCGGGGGCA

exon_4

CAGGTCGAACTCC

GGUCGAACUCC

BCL11A_
+
TTTG
556
AACGTCTTGCCGCAGAA
1867
AACGUCUUGCCGCAGAACU

exon_4

CTCGCATGACTTG

CGCAUGACUUG

BCL11A_
+
CTTG
557
CCGCAGAACTCGCATGA
1868
CCGCAGAACUCGCAUGACU

exon_4

CTTGGACTTGACC

UGGACUUGACC

BCL11A_
+
CTTG
558
GACTTGACCGGGGGCTG
1869
GACUUGACCGGGGGCUGGG

exon_4

GGAGGGAGGAGGG

AGGGAGGAGGG

BCL11A_
+
CTTG
559
ACCGGGGGCTGGGAGGG
1870
ACCGGGGGCUGGGAGGGAG

exon 4

AGGAGGGGCGGAT

GAGGGGCGGAU

BCL11A_
+
ATTG
560
CAGAGGAGGGAGGGGGG
1871
CAGAGGAGGGAGGGGGGGC

exon 4

GCGTCGCCAGGAA

GUCGCCAGGAA

BCL11A_
+
CTTG
561
CTACCTGGCTGGAATGG
1872
CUACCUGGCUGGAAUGGUU

exon 4

TTGCAGTAACCTT

GCAGUAACCUU

BCL11A_
+
GTTG
562
CAGTAACCTTTGCATAG
1873
CAGUAACCUUUGCAUAGGG

exon_4

GGCTGGGCCGGCC

CUGGGCCGGCC

BCL11A_
+
CTTT
563
GCATAGGGCTGGGCCGG
1874
GCAUAGGGCUGGGCCGGCC

exon_4

CCTGGGGACAGCG

UGGGGACAGCG

BCL11A_
+
TTTG
564
CATAGGGCTGGGCCGGC
1875
CAUAGGGCUGGGCCGGCCU

exon_4

CTGGGGACAGCGG

GGGGACAGCGG

BCL11A_
+
GTTC
565
CCTGCCAGCTCTCTAAG
1876
CCUGCCAGCUCUCUAAGUC

exon_4

TCTCCTAGAGAAA

UCCUAGAGAAA

BCL11A_
+
ATTG
566
GATTCAACCGCAGCACC
1877
GAUUCAACCGCAGCACCCU

exon_4

CTGTCAAAGGCAC

GUCAAAGGCAC

BCL11A_
+
ATTC
567
AACCGCAGCACCCTGTC
1878
AACCGCAGCACCCUGUCAA

exon_4

AAAGGCACTCGGG

AGGCACUCGGG

BCL11A_
+
CTTC
568
CGCCCCCAGGCGCTCTA
1879
CGCCCCCAGGCGCUCUAUG

exon_4

TGCGGTGGGGGTC

CGGUGGGGGUC

BCL11A_
+
CTTC
569
TGCCAGGCCGGAAGCCT
1880
UGCCAGGCCGGAAGCCUCU

exon_4

CTCTCGATACTGA

CUCGAUACUGA

BCL11A_
+
ATTC
570
TTAGCAGGTTAAAGGGG
1881
UUAGCAGGUUAAAGGGGUU

exon_4

TTATTGTCTGCAA

AUUGUCUGCAA

BCL11A_
+
CTTA
571
GCAGGTTAAAGGGGTTA
1882
GCAGGUUAAAGGGGUUAUU

exon_4

TTGTCTGCAATAT

GUCUGCAAUAU

BCL11A_
+
GTTA
572
AAGGGGTTATTGTCTGC
1883
AAGGGGUUAUUGUCUGCAA

exon 4

AATATGAATCCCA

UAUGAAUCCCA

BCL11A_
+
GTTG
573
TACATGTGTAGCTGCTG
1884
UACAUGUGUAGCUGCUGGG

exon_4

GGCTCATCTTTAC

CUCAUCUUUAC

BCL11A_
+
TTTG
574
CAAGTTGTACATGTGTA
1885
CAAGUUGUACAUGUGUAGC

exon_4

GCTGCTGGGCTCA

UGCUGGGCUCA

BCL11A_
+
GTTT
575
GCAAGTTGTACATGTGT
1886
GCAAGUUGUACAUGUGUAG

exon_4

AGCTGCTGGGCTC

CUGCUGGGCUC

BCL11A_
+
GTTG
576
CAAGAGAAACCATGCAC
1887
CAAGAGAAACCAUGCACUG

exon 4

TGGTGAATGGCTG

GUGAAUGGCUG

BCL11A_
+
GTTC
577
TGTGCGTGTTGCAAGAG
1888
UGUGCGUGUUGCAAGAGAA

exon_4

AAACCATGCACTG

ACCAUGCACUG

BCL11A_
+
CTTA
578
ATCCATGAGTGTTCTGT
1889
AUCCAUGAGUGUUCUGUGC

exon_4

GCGTGTTGCAAGA

GUGUUGCAAGA

BCL11A_
+
ATTT
579
GAACGTCTTGCCGCAGA
1890
GAACGUCUUGCCGCAGAAC

exon_4

ACTCGCATGACTT

UCGCAUGACUU

BCL11A_
+
ATTC
580
TTAATCCATGAGTGTTC
1891
UUAAUCCAUGAGUGUUCUG

exon 4

TGTGCGTGTTGCA

UGCGUGUUGCA

BCL11A_
+
CTTT
581
CTAAGTAGATTCTTAAT
1892
CUAAGUAGAUUCUUAAUCC

exon 4

CCATGAGTGTTCT

AUGAGUGUUCU

BCL11A_
+
GTTC
582
GCTTTCTAAGTAGATTC
1893
GCUUUCUAAGUAGAUUCUU

exon_4

TTAATCCATGAGT

AAUCCAUGAGU

BCL11A_
+
CTTC
583
CGTGTTCGCTTTCTAAG
1894
CGUGUUCGCUUUCUAAGUA

exon_4

TAGATTCTTAATC

GAUUCUUAAUC

BCL11A_
+
ATTC
584
TGCACCTAGTCCTGAAG
1895
UGCACCUAGUCCUGAAGGG

exon_4

GGATACCAACCCG

AUACCAACCCG

BCL11A_
+
ATTG
585
TCTGCAATATGAATCCC
1896
UCUGCAAUAUGAAUCCCAU

exon_4

ATGGAGAGGTGGC

GGAGAGGUGGC

BCL11A_
+
GTTA
586
TTGTCTGCAATATGAAT
1897
UUGUCUGCAAUAUGAAUCC

exon_4

CCCATGGAGAGGT

CAUGGAGAGGU

BCL11A_
+
TTTC
587
TAAGTAGATTCTTAATC
1898
UAAGUAGAUUCUUAAUCCA

exon_4

CATGAGTGTTCTG

UGAGUGUUCUG

BCL11A_
+
TTTA
588
AAATAGCCATAACATAC
1899
AAAUAGCCAUAACAUACCA

exon_4

CATACATGCTGTC

UACAUGCUGUC

BCL11A_
+
GTTG
589
CTCTGAAATTTGAACGT
1900
CUCUGAAAUUUGAACGUCU

exon_4

CTTGCCGCAGAAC

UGCCGCAGAAC

BCL11A_
+
CTTG
590
TAGGGCTTCTCGCCCGT
1901
UAGGGCUUCUCGCCCGUGU

exon_4

GTGGCTGCGCCGG

GGCUGCGCCGG

BCL11A_
+
CTTC
591
TCGAGCTTGATGCGCTT
1902
UCGAGCUUGAUGCGCUUAG

exon_4

AGAGAAGGGGCTC

AGAAGGGGCUC

BCL11A_
+
CTTG
592
ATGCGCTTAGAGAAGGG
1903
AUGCGCUUAGAGAAGGGGC

exon_4

GCTCAGCGAGCTG

UCAGCGAGCUG

BCL11A_
+
CTTA
593
GAGAAGGGGCTCAGCGA
1904
GAGAAGGGGCUCAGCGAGC

exon_4

GCTGGGGCTGCCC

UGGGGCUGCCC

BCL11A_
+
CTTT
594
TTGGACAGGCCCCCCGA
1905
UUGGACAGGCCCCCCGAGG

exon_4

GGCCGACTCGCCC

CCGACUCGCCC

BCL11A_
+
TTTT
595
TGGACAGGCCCCCCGAG
1906
UGGACAGGCCCCCCGAGGC

exon_4

GCCGACTCGCCCG

CGACUCGCCCG

BCL11A_
+
TTTT
596
GGACAGGCCCCCCGAGG
1907
GGACAGGCCCCCCGAGGCC

exon 4

CCGACTCGCCCGG

GACUCGCCCGG

BCL11A_
+
TTTG
597
GACAGGCCCCCCGAGGC
1908
GACAGGCCCCCCGAGGCCG

exon_4

CGACTCGCCCGGG

ACUCGCCCGGG

BCL11A_
+
ATTA
598
ACAGTGCCATCGTCTAT
1909
ACAGUGCCAUCGUCUAUGC

exon 4

GCGGTCCGACTCG

GGUCCGACUCG

BCL11A_
+
CTTC
599
GTCGCAAGTGTCCCTGT
1910
GUCGCAAGUGUCCCUGUGG

exon_4

GGCCCTCGGCCTC

CCCUCGGCCUC

BCL11A_
+
CTTA
600
TGCTTCTCGCCCAGGAC
1911
UGCUUCUCGCCCAGGACCU

exon_4

CTGGTGGAAGGCC

GGUGGAAGGCC

BCL11A_
+
CTTC
601
TCGCCCAGGACCTGGTG
1912
UCGCCCAGGACCUGGUGGA

exon_4

GAAGGCCTCGCTG

AGGCCUCGCUG

BCL11A_
+
GTTC
602
TCGTGGTGGCGCGCCGC
1913
UCGUGGUGGCGCGCCGCCU

exon_4

CTCCAGGCTCAGC

CCAGGCUCAGC

BCL11A_
+
CTTC
603
CTCCTCTTCTTCCTCTT
1914
CUCCUCUUCUUCCUCUUCC

exon_4

CCTCGTCGTCCTC

UCGUCGUCCUC

BCL11A_
+
CTTC
604
TTCCTCTTCCTCGTCGT
1915
UUCCUCUUCCUCGUCGUCC

exon_4

CCTCCTCTTCCTC

UCCUCUUCCUC

BCL11A_
+
CTTC
605
CTCTTCCTCGTCGTCCT
1916
CUCUUCCUCGUCGUCCUCC

exon_4

CCTCTTCCTCCTC

UCUUCCUCCUC

BCL11A_
+
CTTC
606
CTCGTCGTCCTCCTCTT
1917
CUCGUCGUCCUCCUCUUCC

exon_4

CCTCCTCGTCCCC

UCCUCGUCCCC

BCL11A_
+
CTTC
607
CTCCTCGTCCCCGTTCT
1918
CUCCUCGUCCCCGUUCUCC

exon_4

CCGGGATCAGGTT

GGGAUCAGGUU

BCL11A_
+
GTTG
608
CACTTGTAGGGCTTCTC
1919
CACUUGUAGGGCUUCUCGC

exon_4

GCCCGTGTGGCTG

CCGUGUGGCUG

BCL11A_
+
CTTG
609
CTGGCCTGGGTGCACGC
1920
CUGGCCUGGGUGCACGCGU

exon 4

GTGGTCGCACAGG

GGUCGCACAGG

BCL11A_
+
CTTC
610
AGCTTGCTGGCCTGGGT
1921
AGCUUGCUGGCCUGGGUGC

exon_4

GCACGCGTGGTCG

ACGCGUGGUCG

BCL11A_
+
CTTC
611
ATGTGGCGCTTCAGCTT
1922
AUGUGGCGCUUCAGCUUGC

exon_4

GCTGGCCTGGGTG

UGGCCUGGGUG

BCL11A_
+
TTTG
612
TGCATGTGCGTCTTCAT
1923
UGCAUGUGCGUCUUCAUGU

exon_4

GTGGCGCTTCAGC

GGCGCUUCAGC

BCL11A_
+
ATTT
613
GTGCATGTGCGTCTTCA
1924
GUGCAUGUGCGUCUUCAUG

exon_4

TGTGGCGCTTCAG

UGGCGCUUCAG

BCL11A_
+
CTTC
614
TCGCCCGTGTGGCTGCG
1925
UCGCCCGUGUGGCUGCGCC

exon_4

CCGGTGCACCACC

GGUGCACCACC

BCL11A_
+
CTTG
615
ACCGTCATGGGGGACGA
1926
ACCGUCAUGGGGGACGAUU

exon_4

TTTGTGCATGTGC

UGUGCAUGUGC

BCL11A_
+
CTTG
616
AGCGCGCTGCTGGCGCT
1927
AGCGCGCUGCUGGCGCUGC

exon_4

GCCCACCAAGTCG

CCACCAAGUCG

BCL11A_
+
CTTG
617
GCCACCACGGACTTGAG
1928
GCCACCACGGACUUGAGCG

exon_4

CGCGCTGCTGGCG

CGCUGCUGGCG

BCL11A_
+
CTTG
618
AACTTGGCCACCACGGA
1929
AACUUGGCCACCACGGACU

exon_4

CTTGAGCGCGCTG

UGAGCGCGCUG

BCL11A_
+
GTTC
619
TCGCTCTTGAACTTGGC
1930
UCGCUCUUGAACUUGGCCA

exon_4

CACCACGGACTTG

CCACGGACUUG

BCL11A_
+
GTTG
620
GGGTCGTTCTCGCTCTT
1931
GGGUCGUUCUCGCUCUUGA

exon_4

GAACTTGGCCACC

ACUUGGCCACC

BCL11A_
+
GTTC
621
TCCGGGATCAGGTTGGG
1932
UCCGGGAUCAGGUUGGGGU

exon_4

GTCGTTCTCGCTC

CGUUCUCGCUC

BCL11A_
+
GTTC
622
CGGGGAGCTGGCGGTGG
1933
CGGGGAGCUGGCGGUGGAG

exon_4

AGAGACCGTCGTC

AGACCGUCGUC

BCL11A_
+
ATTT
623
AAAATAGCCATAACATA
1934
AAAAUAGCCAUAACAUACC

exon_4

CCATACATGCTGT

AUACAUGCUGU

BCL11A_
+
ATTA
624
GGGACAATTTAAAATAG
1935
GGGACAAUUUAAAAUAGCC

exon_4

CCATAACATACCA

AUAACAUACCA

BCL11A_
+
TTTG
625
CTCAGCAACGAATTAGG
1936
CUCAGCAACGAAUUAGGGA

exon_4

GACAATTTAAAAT

CAAUUUAAAAU

BCL11A_
+
CTTA
626
CTAGTGTATTTAATTGC
1937
CUAGUGUAUUUAAUUGCGU

exon_4

GTTCCAGGGCTTT

UCCAGGGCUUU

BCL11A_
+
ATTT
627
AATTGCGTTCCAGGGCT
1938
AAUUGCGUUCCAGGGCUUU

exon_4

TTTGCACATTACA

UGCACAUUACA

BCL11A_
+
TTTA
628
ATTGCGTTCCAGGGCTT
1939
AUUGCGUUCCAGGGCUUUU

exon_4

TTGCACATTACAC

GCACAUUACAC

BCL11A_
+
ATTG
629
CGTTCCAGGGCTTTTGC
1940
CGUUCCAGGGCUUUUGCAC

exon_4

ACATTACACATTC

AUUACACAUUC

BCL11A_
+
GTTC
630
CAGGGCTTTTGCACATT
1941
CAGGGCUUUUGCACAUUAC

exon_4

ACACATTCAATTT

ACAUUCAAUUU

BCL11A_
+
CTTT
631
TGCACATTACACATTCA
1942
UGCACAUUACACAUUCAAU

exon_4

ATTTAATCATTGT

UUAAUCAUUGU

BCL11A_
+
TTTT
632
GCACATTACACATTCAA
1943
GCACAUUACACAUUCAAUU

exon_4

TTTAATCATTGTT

UAAUCAUUGUU

BCL11A_
+
TTTG
633
CACATTACACATTCAAT
1944
CACAUUACACAUUCAAUUU

exon_4

TTAATCATTGTTT

AAUCAUUGUUU

BCL11A_
+
ATTA
634
CACATTCAATTTAATCA
1945
CACAUUCAAUUUAAUCAUU

exon_4

TTGTTTAAAAAAA

GUUUAAAAAAA

BCL11A_
+
ATTC
635
AATTTAATCATTGTTTA
1946
AAUUUAAUCAUUGUUUAAA

exon_4

AAAAAAATAAAAC

AAAAAAAAAC

BCL11A_
+
ATTT
636
AATCATTGTTTAAAAAA
1947
AAUCAUUGUUUAAAAAAAA

exon_4

AATAAAACTTTGG

UAAAACUUUGG

BCL11A_
+
TTTA
637
ATCATTGTTTAAAAAAA
1948
AUCAUUGUUUAAAAAAAAU

exon_4

ATAAAACTTTGGG

AAAACUUUGGG

BCL11A_
+
ATTG
638
TTTAAAAAAAATAAAAC
1949
UUUAAAAAAAAUAAAACUU

exon 4

TTTGGGCAAAACA

UGGGCAAAACA

BCL11A_
+
GTTT
639
AAAAAAAATAAAACTTT
1950
AAAAAAAAUAAAACUUUGG

exon_4

GGGCAAAACAGCC

GCAAAACAGCC

BCL11A_
+
TTTA
640
AAAAAAATAAAACTTTG
1951
AAAAAAAUAAAACUUUGGG

exon_4

GGCAAAACAGCCC

CAAAACAGCCC

BCL11A_
+
CTTT
641
GGGCAAAACAGCCCATT
1952
GGGCAAAACAGCCCAUUUC

exon_4

TCTTTTAAGCTCT

UUUUAAGCUCU

BCL11A_
+
TTTG
642
GGCAAAACAGCCCATTT
1953
GGCAAAACAGCCCAUUUCU

exon_4

CTTTTAAGCTCTC

UUUAAGCUCUC

BCL11A_
+
ATTA
643
AACTAAAGGAAAAATGA
1954
AACUAAAGGAAAAAUGAUG

exon_4

TGATTAACTAGGA

AUUAACUAGGA

BCL11A_
+
TTTA
644
TAAAATTAAACTAAAGG
1955
UAAAAUUAAACUAAAGGAA

exon_4

AAAAATGATGATT

AAAUGAUGAUU

BCL11A_
+
GTTT
645
ATAAAATTAAACTAAAG
1956
AUAAAAUUAAACUAAAGGA

exon_4

GAAAAATGATGAT

AAAAUGAUGAU

BCL11A_
+
TTTG
646
TTTATAAAATTAAACTA
1957
UUUAUAAAAUUAAACUAAA

exon_4

AAGGAAAAATGAT

GGAAAAAUGAU

BCL11A_
+
TTTT
647
GTTTATAAAATTAAACT
1958
GUUUAUAAAAUUAAACUAA

exon_4

AAAGGAAAAATGA

AGGAAAAAUGA

BCL11A_
+
GTTT
648
TGTTTATAAAATTAAAC
1959
UGUUUAUAAAAUUAAACUA

exon_4

TAAAGGAAAAATG

AAGGAAAAAUG

BCL11A_
+
CTTC
649
ATAAAATGAACTCCTTA
1960
AUAAAAUGAACUCCUUACU

exon_4

CTAGTGTATTTAA

AGUGUAUUUAA

BCL11A_
+
TTTA
650
TACTGGTATAATCAGTT
1961
UACUGGUAUAAUCAGUUUU

exon_4

TTGTTTATAAAAT

GUUUAUAAAAU

BCL11A_
+
CTTT
651
TATACTGGTATAATCAG
1962
UAUACUGGUAUAAUCAGUU

exon_4

TTTTGTTTATAAA

UUGUUUAUAAA

BCL11A_
+
TTTA
652
AGCTCTCACCAGGAGCA
1963
AGCUCUCACCAGGAGCAAA

exon_4

AAGTAGCTTTTAT

GUAGCUUUUAU

BCL11A_
+
TTTT
653
AAGCTCTCACCAGGAGC
1964
AAGCUCUCACCAGGAGCAA

exon_4

AAAGTAGCTTTTA

AGUAGCUUUUA

BCL11A_
+
CTTT
654
TAAGCTCTCACCAGGAG
1965
UAAGCUCUCACCAGGAGCA

exon_4

CAAAGTAGCTTTT

AAGUAGCUUUU

BCL11A_
+
TTTC
655
TTTTAAGCTCTCACCAG
1966
UUUUAAGCUCUCACCAGGA

exon_4

GAGCAAAGTAGCT

GCAAAGUAGCU

BCL11A_
+
ATTT
656
CTTTTAAGCTCTCACCA
1967
CUUUUAAGCUCUCACCAGG

exon_4

GGAGCAAAGTAGC

AGCAAAGUAGC

BCL11A_
+
TTTT
657
ATACTGGTATAATCAGT
1968
AUACUGGUAUAAUCAGUUU

exon 4

TTTGTTTATAAAA

UGUUUAUAAAA

BCL11A_
+
ATTA
658
ACTAGGACATAATGGGT
1969
ACUAGGACAUAAUGGGUCA

exon_4

CATCTTTTTAGGT

UCUUUUUAGGU

BCL11A_
+
ATTA
659
AAGCAAATATCTTCATA
1970
AAGCAAAUAUCUUCAUAAA

exon_4

AAATGAACTCCTT

AUGAACUCCUU

BCL11A_
+
TTTA
660
AAAAGACATTATTAAAG
1971
AAAAGACAUUAUUAAAGCA

exon_4

CAAATATCTTCAT

AAUAUCUUCAU

BCL11A_
+
GTTC
661
TAGTTTTAAATGGCAAA
1972
UAGUUUUAAAUGGCAAAUA

exon_4

TAGTACCACGTTG

GUACCACGUUG

BCL11A_
+
GTTT
662
TAAATGGCAAATAGTAC
1973
UAAAUGGCAAAUAGUACCA

exon_4

CACGTTGTGCTAA

CGUUGUGCUAA

BCL11A_
+
TTTT
663
AAATGGCAAATAGTACC
1974
AAAUGGCAAAUAGUACCAC

exon_4

ACGTTGTGCTAAT

GUUGUGCUAAU

BCL11A_
+
TTTA
664
AATGGCAAATAGTACCA
1975
AAUGGCAAAUAGUACCACG

exon_4

CGTTGTGCTAATA

UUGUGCUAAUA

BCL11A_
+
GTTG
665
TGCTAATAAATCATATT
1976
UGCUAAUAAAUCAUAUUAU

exon 4

ATTTTCTTCTGTT

UUUCUUCUGUU

BCL11A_
+
ATTA
666
TTTTCTTCTGTTCCCCT
1977
UUUUCUUCUGUUCCCCUCU

exon 4

CTGTCAAACCTTA

GUCAAACCUUA

BCL11A_
+
ATTT
667
TCTTCTGTTCCCCTCTG
1978
UCUUCUGUUCCCCUCUGUC

exon 4

TCAAACCTTATTG

AAACCUUAUUG

BCL11A_
+
TTTT
668
CTTCTGTTCCCCTCTGT
1979
CUUCUGUUCCCCUCUGUCA

exon_4

CAAACCTTATTGT

AACCUUAUUGU

BCL11A_
+
TTTC
669
TTCTGTTCCCCTCTGTC
1980
UUCUGUUCCCCUCUGUCAA

exon_4

AAACCTTATTGTC

ACCUUAUUGUC

BCL11A_
+
CTTC
670
TGTTCCCCTCTGTCAAA
1981
UGUUCCCCUCUGUCAAACC

exon_4

CCTTATTGTCAGC

UUAUUGUCAGC

BCL11A_
+
GTTC
671
CCCTCTGTCAAACCTTA
1982
CCCUCUGUCAAACCUUAUU

exon_4

TTGTCAGCCTCTT

GUCAGCCUCUU

BCL11A_
+
CTTA
672
TTGTCAGCCTCTTCCTT
1983
UUGUCAGCCUCUUCCUUUC

exon 4

TCAATATGGTATA

AAUAUGGUAUA

BCL11A_
+
ATTG
673
TCAGCCTCTTCCTTTCA
1984
UCAGCCUCUUCCUUUCAAU

exon 4

ATATGGTATACAA

AUGGUAUACAA

BCL11A_
+
CTTC
674
CTTTCAATATGGTATAC
1985
CUUUCAAUAUGGUAUACAA

exon 4

AAGGTCTTAAAGT

GGUCUUAAAGU

BCL11A_
+
CTTT
675
CAATATGGTATACAAGG
1986
CAAUAUGGUAUACAAGGUC

exon 4

TCTTAAAGTTTAT

UUAAAGUUUAU

BCL11A_
−
TTTC
676
AATATGGTATACAAGGT
1987
AAUAUGGUAUACAAGGUCU

exon_4

CTTAAAGTTTATC

UAAAGUUUAUC

BCL11A_
+
CTTA
677
AAGTTTATCATTTGATT
1988
AAGUUUAUCAUUUGAUUGU

exon_4

GTCCACTTGACAA

CCACUUGACAA

BCL11A_
+
TTTT
678
AAAAAGACATTATTAAA
1989
AAAAAGACAUUAUUAAAGC

exon_4

GCAAATATCTTCA

AAAUAUCUUCA

BCL11A_
+
TTTT
679
TAAAAAGACATTATTAA
1990
UAAAAAGACAUUAUUAAAG

exon_4

AGCAAATATCTTC

CAAAUAUCUUC

BCL11A_
+
ATTT
680
TTAAAAAGACATTATTA
199
UUAAAAAGACAUUAUUAAA

exon 4

AAGCAAATATCTT

GCAAAUAUCUU

BCL11A_
+
TTTG
681
GTGCCAGTATTTTTAAA
1992
GUGCCAGUAUUUUUAAAAA

exon_4

AAGACATTATTAA

GACAUUAUUAA

BCL11A_
+
TTTT
682
GGTGCCAGTATTTTTAA
1993
GGUGCCAGUAUUUUUAAAA

exon 4

AAAGACATTATTA

AGACAUUAUUA

BCL11A_
+
CTTT
683
TGGTGCCAGTATTTTTA
1994
UGGUGCCAGUAUUUUUAAA

exon_4

AAAAGACATTATT

AAGACAUUAUU

BCL11A_
+
ATTA
684
TTAAAGCAAATATCTTC
1995
UUAAAGCAAAUAUCUUCAU

exon 4

ATAAAATGAACTC

AAAAUGAACUC

BCL11A_
+
TTTC
685
TTTTGGTGCCAGTATTT
1996
UUUUGGUGCCAGUAUUUUU

exon_4

TTAAAAAGACATT

AAAAAGACAUU

BCL11A_
+
CTTG
686
ACAACCAAGTAGATCTG
1997
ACAACCAAGUAGAUCUGGA

exon_4

GATCTATTTCTTT

UCUAUUUCUUU

BCL11A_
+
ATTG
687
TCCACTTGACAACCAAG
1998
UCCACUUGACAACCAAGUA

exon_4

TAGATCTGGATCT

GAUCUGGAUCU

BCL11A_
+
TTTG
688
ATTGTCCACTTGACAAC
1999
AUUGUCCACUUGACAACCA

exon_4

CAAGTAGATCTGG

AGUAGAUCUGG

BCL11A_
+
ATTT
689
GATTGTCCACTTGACAA
2000
GAUUGUCCACUUGACAACC

exon 4

CCAAGTAGATCTG

AAGUAGAUCUG

BCL11A_
+
TTTA
690
TCATTTGATTGTCCACT
2001
UCAUUUGAUUGUCCACUUG

exon 4

TGACAACCAAGTA

ACAACCAAGUA

BCL11A_
+
GTTT
691
ATCATTTGATTGTCCAC
2002
AUCAUUUGAUUGUCCACUU

exon_4

TTGACAACCAAGT

GACAACCAAGU

BCL11A_
+
ATTT
692
CTTTTGGTGCCAGTATT
2003
CUUUUGGUGCCAGUAUUUU

exon_4

TTTAAAAAGACAT

UAAAAAGACAU

BCL11A_
+
ATTA
693
GCTTATATACCTGTTCT
2004
GCUUAUAUACCUGUUCUAG

exon_4

AGTTTTAAATGGC

UUUUAAAUGGC

BCL11A_
+
CTTT
694
TTAGGTAGCCATTGTTG
2005
UUAGGUAGCCAUUGUUGUG

exon_4

TGAGAAATACAAT

AGAAAUACAAU

BCL11A_
+
TTTT
695
AGGTAGCCATTGTTGTG
2006
AGGUAGCCAUUGUUGUGAG

exon_4

AGAAATACAATAT

AAAUACAAUAU

BCL11A_
+
ATTG
696
ATACATTTAACCCTTTA
2007
AUACAUUUAACCCUUUAGA

exon 4

GAGACAGACATTT

GACAGACAUUU

BCL11A_
+
ATTT
697
AACCCTTTAGAGACAGA
2008
AACCCUUUAGAGACAGACA

exon_4

CATTTAGCTCATA

UUUAGCUCAUA

BCL11A_
+
TTTA
698
ACCCTTTAGAGACAGAC
2009
ACCCUUUAGAGACAGACAU

exon_4

ATTTAGCTCATAG

UUAGCUCAUAG

BCL11A_
+
CTTT
699
AGAGACAGACATTTAGC
2010
AGAGACAGACAUUUAGCUC

exon_4

TCATAGAGATTTT

AUAGAGAUUUU

BCL11A_
+
TTTA
700
GAGACAGACATTTAGCT
2011
GAGACAGACAUUUAGCUCA

exon_4

CATAGAGATTTTT

UAGAGAUUUUU

BCL11A_
+
ATTT
701
AGCTCATAGAGATTTTT
2012
AGCUCAUAGAGAUUUUUUU

exon_4

TTTCAGTGCTATC

UCAGUGCUAUC

BCL11A_
+
TTTA
702
GCTCATAGAGATTTTTT
2013
GCUCAUAGAGAUUUUUUUU

exon 4

TTCAGTGCTATCT

CAGUGCUAUCU

BCL11A_
+
ATTT
703
TTTTTCAGTGCTATCTA
2014
UUUUUCAGUGCUAUCUAUU

exon 4

TTCTGTCTATAGA

CUGUCUAUAGA

BCL11A_
+
TTTT
704
TTTTCAGTGCTATCTAT
2015
UUUUCAGUGCUAUCUAUUC

exon 4

TCTGTCTATAGAG

UGUCUAUAGAG

BCL11A_
+
TTTT
705
TTTCAGTGCTATCTATT
2016
UUUCAGUGCUAUCUAUUCU

exon_4

CTGTCTATAGAGG

GUCUAUAGAGG

BCL11A_
+
TTTT
706
TTCAGTGCTATCTATTC
2017
UUCAGUGCUAUCUAUUCUG

exon 4

TGTCTATAGAGGG

UCUAUAGAGGG

BCL11A_
+
TTTT
707
TCAGTGCTATCTATTCT
2018
UCAGUGCUAUCUAUUCUGU

exon_4

GTCTATAGAGGGT

CUAUAGAGGGU

BCL11A_
+
TTTT
708
CAGTGCTATCTATTCTG
2019
CAGUGCUAUCUAUUCUGUC

exon 4

TCTATAGAGGGTT

UAUAGAGGGUU

BCL11A_
+
TTTC
709
AGTGCTATCTATTCTGT
2020
AGUGCUAUCUAUUCUGUCU

exon_4

CTATAGAGGGTTA

AUAGAGGGUUA

BCL11A_
+
ATTC
710
TGTCTATAGAGGGTTAA
2021
UGUCUAUAGAGGGUUAAUC

exon 4

TCCAAAGACTGTT

CAAAGACUGUU

BCL11A_
+
GTTA
711
ATCCAAAGACTGTTTTT
2022
AUCCAAAGACUGUUUUUCC

exon 4

CCTCCTCACGTTA

UCCUCACGUUA

BCL11A_
+
GTTT
712
TTCCTCCTCACGTTATA
2023
UUCCUCCUCACGUUAUAAA

exon_4

AAATAAAACTGTA

AUAAAACUGUA

BCL11A_
+
GTTT
713
GCTCAGCAACGAATTAG
2024
GCUCAGCAACGAAUUAGGG

exon_4

GGACAATTTAAAA

ACAAUUUAAAA

BCL11A_
+
TTTC
714
TCTCAGAACGGAACTGG
2025
UCUCAGAACGGAACUGGAA

exon 4

AAACAGCAACATG

ACAGCAACAUG

BCL11A_
+
TTTT
715
CTCTCAGAACGGAACTG
2026
CUCUCAGAACGGAACUGGA

exon 4

GAAACAGCAACAT

AACAGCAACAU

BCL11A_
+
TTTT
716
TCTCTCAGAACGGAACT
2027
UCUCUCAGAACGGAACUGG

exon 4

GGAAACAGCAACA

AAACAGCAACA

BCL11A_
+
CTTT
717
TTCTCTCAGAACGGAAC
2028
UUCUCUCAGAACGGAACUG

exon 4

TGGAAACAGCAAC

GAAACAGCAAC

BCL11A_
+
TTTC
718
TCTCTCTCTCTCTTTTT
2029
UCUCUCUCUCUCUUUUUCU

exon_4

CTCTCAGAACGGA

CUCAGAACGGA

BCL11A_
+
TTTC
719
CAATTGATACATTTAAC
2030
CAAUUGAUACAUUUAACCC

exon_4

CCTTTAGAGACAG

UUUAGAGACAG

BCL11A_
+
TTTT
720
CTCTCTCTCTCTCTTTT
2031
CUCUCUCUCUCUCUUUUUC

exon_4

TCTCTCAGAACGG

UCUCAGAACGG

BCL11A_
+
CTTT
721
TTCTCTCTCTCTCTCTT
2032
UUCUCUCUCUCUCUCUUUU

exon_4

TTTCTCTCAGAAC

UCUCUCAGAAC

BCL11A_
+
ATTA
722
CAGAATGTATGCAGCAT
2033
CAGAAUGUAUGCAGCAUGG

exon_4

GGTCTTTTTCTCT

UCUUUUUCUCU

BCL11A_
+
GTTA
723
TAAAATAAAACTGTACA
2034
UAAAAUAAAACUGUACAUG

exon_4

TGATATGTATTAC

AUAUGUAUUAC

BCL11A_
+
TTTC
724
CTCCTCACGTTATAAAA
2035
CUCCUCACGUUAUAAAAUA

exon_4

TAAAACTGTACAT

AAACUGUACAU

BCL11A_
+
TTTT
725
CCTCCTCACGTTATAAA
2036
CCUCCUCACGUUAUAAAAU

exon 4

ATAAAACTGTACA

AAAACUGUACA

BCL11A_
+
TTTT
726
TCCTCCTCACGTTATAA
2037
UCCUCCUCACGUUAUAAAA

exon_4

AATAAAACTGTAC

UAAAACUGUAC

BCL11A_
+
TTTT
727
TCTCTCTCTCTCTCTTT
2038
UCUCUCUCUCUCUCUUUUU

exon_4

TTCTCTCAGAACG

CUCUCAGAACG

BCL11A_
+
TTTT
728
TAGGTAGCCATTGTTGT
2039
UAGGUAGCCAUUGUUGUGA

exon_4

GAGAAATACAATA

GAAAUACAAUA

BCL11A_
+
CTTT
729
CCAATTGATACATTTAA
2040
CCAAUUGAUACAUUUAACC

exon_4

CCCTTTAGAGACA

CUUUAGAGACA

BCL11A_
+
TTTC
730
TTCCTTTCCAATTGATA
2041
UUCCUUUCCAAUUGAUACA

exon_4

CATTTAACCCTTT

UUUAACCCUUU

BCL11A_
+
TTTA
731
GGTAGCCATTGTTGTGA
2042
GGUAGCCAUUGUUGUGAGA

exon 4

GAAATACAATATA

AAUACAAUAUA

BCL11A_
+
ATTG
732
TTGTGAGAAATACAATA
2043
UUGUGAGAAAUACAAUAUA

exon 4

TAGAATTATATGC

GAAUUAUAUGC

BCL11A_
+
GTTG
733
TGAGAAATACAATATAG
2044
UGAGAAAUACAAUAUAGAA

exon 4

AATTATATGCTAG

UUAUAUGCUAG

BCL11A_
+
ATTA
734
TATGCTAGTTCCTAAGG
2045
UAUGCUAGUUCCUAAGGUU

exon 4

TTTATTACCTCAC

UAUUACCUCAC

BCL11A_
+
GTTC
735
CTAAGGTTTATTACCTC
2046
CUAAGGUUUAUUACCUCAC

exon 4

ACCCAATGCTGAA

CCAAUGCUGAA

BCL11A_
+
GTTT
736
ATTACCTCACCCAATGC
2047
AUUACCUCACCCAAUGCUG

exon 4

TGAATTAAGCTAC

AAUUAAGCUAC

BCL11A_
+
TTTA
737
TTACCTCACCCAATGCT
2048
UUACCUCACCCAAUGCUGA

exon_4

GAATTAAGCTACA

AUUAAGCUACA

BCL11A_
+
ATTA
738
CCTCACCCAATGCTGAA
2049
CCUCACCCAAUGCUGAAUU

exon_4

TTAAGCTACAAGT

AAGCUACAAGU

BCL11A_
+
ATTA
739
AGCTACAAGTTTATAAC
2050
AGCUACAAGUUUAUAACAA

exon_4

AAGTAGAAAGAAC

GUAGAAAGAAC

BCL11A_
+
GTTT
740
ATAACAAGTAGAAAGAA
2051
AUAACAAGUAGAAAGAACC

exon_4

CCATCGATGTGGT

AUCGAUGUGGU

BCL11A_
+
TTTA
741
TAACAAGTAGAAAGAAC
2052
UAACAAGUAGAAAGAACCA

exon_4

CATCGATGTGGTT

UCGAUGUGGUU

BCL11A_
+
GTTT
742
TAATAGATCCAAGGCAC
2053
UAAUAGAUCCAAGGCACUC

exon_4

TCATATTTTAAAA

AUAUUUUAAAA

BCL11A_
+
TTTT
743
AATAGATCCAAGGCACT
2054
AAUAGAUCCAAGGCACUCA

exon 4

CATATTTTAAAAC

UAUUUUAAAAC

BCL11A_
+
TTTA
744
ATAGATCCAAGGCACTC
2055
AUAGAUCCAAGGCACUCAU

exon 4

ATATTTTAAAACC

AUUUUAAAACC

BCL11A_
+
ATTT
745
TAAAACCAAATGATAGA
2056
UAAAACCAAAUGAUAGAAU

exon 4

ATAAACTTGTTCT

AAACUUGUUCU

BCL11A_
+
TTTT
746
AAAACCAAATGATAGAA
2057
AAAACCAAAUGAUAGAAUA

exon 4

TAAACTTGTTCTG

AACUUGUUCUG

BCL11A_
+
TTTA
747
AAACCAAATGATAGAAT
2058
AAACCAAAUGAUAGAAUAA

exon_4

AAACTTGTTCTGT

ACUUGUUCUGU

BCL11A_
+
TTTT
748
CTTCCTTTCCAATTGAT
2059
CUUCCUUUCCAAUUGAUAC

exon_4

ACATTTAACCCTT

AUUUAACCCUU

BCL11A_
+
TTTT
749
TCTTCCTTTCCAATTGA
2060
UCUUCCUUUCCAAUUGAUA

exon_4

TACATTTAACCCT

CAUUUAACCCU

BCL11A_
+
TTTT
750
TTCTTCCTTTCCAATTG
2061
UUCUUCCUUUCCAAUUGAU

exon_4

ATACATTTAACCC

ACAUUUAACCC

BCL11A_
+
CTTT
751
TTTCTTCCTTTCCAATT
2062
UUUCUUCCUUUCCAAUUGA

exon_4

GATACATTTAACC

UACAUUUAACC

BCL11A_
−
TTTT
752
TGGCAGTTGTCTGCATT
2063
UGGCAGUUGUCUGCAUUAA

exon_4

AACCTGTTCATAC

CCUGUUCAUAC

BCL11A_
+
TTTG
753
TCAATTCAAGGCCTTTT
2064
UCAAUUCAAGGCCUUUUUU

exon 4

TTCTTCCTTTCCA

CUUCCUUUCCA

BCL11A_
+
CTTC
754
CTTTCCAATTGATACAT
2065
CUUUCCAAUUGAUACAUUU

exon 4

TTAACCCTTTAGA

AACCCUUUAGA

BCL11A_
+
ATTT
755
GTCAATTCAAGGCCTTT
2066
GUCAAUUCAAGGCCUUUUU

exon 4

TTTCTTCCTTTCC

UCUUCCUUUCC

BCL11A_
+
TTTC
756
TGTTAATTTGTCAATTC
2067
UGUUAAUUUGUCAAUUCAA

exon_4

AAGGCCTTTTTTC

GGCCUUUUUUC

BCL11A_
+
TTTT
757
CTGTTAATTTGTCAATT
2068
CUGUUAAUUUGUCAAUUCA

exon_4

CAAGGCCTTTTTT

AGGCCUUUUUU

BCL11A_
+
TTTT
758
TCTGTTAATTTGTCAAT
2069
UCUGUUAAUUUGUCAAUUC

exon_4

TCAAGGCCTTTTT

AAGGCCUUUUU

BCL11A_
+
GTTT
759
TTCTGTTAATTTGTCAA
2070
UUCUGUUAAUUUGUCAAUU

exon_4

TTCAAGGCCTTTT

CAAGGCCUUUU

BCL11A_
+
GTTC
760
TGTTTTTCTGTTAATTT
2071
UGUUUUUCUGUUAAUUUGU

exon_4

GTCAATTCAAGGC

CAAUUCAAGGC

BCL11A_
+
CTTG
761
TTCTGTTTTTCTGTTAA
2072
UUCUGUUUUUCUGUUAAUU

exon_4

TTTGTCAATTCAA

UGUCAAUUCAA

BCL11A_
+
GTTA
762
ATTTGTCAATTCAAGGC
2073
AUUUGUCAAUUCAAGGCCU

exon 4

CTTTTTTCTTCCT

UUUUUCUUCCU

BCL11A_
−
TTTT
763
TTGGCAGTTGTCTGCAT
2074
UUGGCAGUUGUCUGCAUUA

exon 4

TAACCTGTTCATA

ACCUGUUCAUA

BCL11A_
−
TTTC
764
CTTCTATCACCCTACAT
2075
CUUCUAUCACCCUACAUUC

exon 4

TCCAGCATCTTAC

CAGCAUCUUAC

BCL11A_
−
GTTT
765
TTTTGGCAGTTGTCTGC
2076
UUUUGGCAGUUGUCUGCAU

exon_4

ATTAACCTGTTCA

UAACCUGUUCA

BCL11A_
−
ATTA
766
ACAGAAAAACAGAACAA
2077
ACAGAAAAACAGAACAAGU

exon_4

GTTTATTCTATCA

UUAUUCUAUCA

BCL11A_
−
GTTT
767
ATTCTATCATTTGGTTT
2078
AUUCUAUCAUUUGGUUUUA

exon_4

TAAAATATGAGTG

AAAUAUGAGUG

BCL11A_
−
TTTA
768
TTCTATCATTTGGTTTT
2079
UUCUAUCAUUUGGUUUUAA

exon_4

AAAATATGAGTGC

AAUAUGAGUGC

BCL11A_
−
ATTC
769
TATCATTTGGTTTTAAA
2080
UAUCAUUUGGUUUUAAAAU

exon_4

ATATGAGTGCCTT

AUGAGUGCCUU

BCL11A_
−
ATTT
770
GGTTTTAAAATATGAGT
2081
GGUUUUAAAAUAUGAGUGC

exon_4

GCCTTGGATCTAT

CUUGGAUCUAU

BCL11A_
−
TTTG
771
GTTTTAAAATATGAGTG
2082
GUUUUAAAAUAUGAGUGCC

exon_4

CCTTGGATCTATT

UUGGAUCUAUU

BCL11A_
−
GTTT
772
TAAAATATGAGTGCCTT
2083
UAAAAUAUGAGUGCCUUGG

exon 4

GGATCTATTAAAA

AUCUAUUAAAA

BCL11A_
−
TTTT
773
AAAATATGAGTGCCTTG
2084
AAAAUAUGAGUGCCUUGGA

exon 4

GATCTATTAAAAC

UCUAUUAAAAC

BCL11A_
−
TTTA
774
AAATATGAGTGCCTTGG
2085
AAAUAUGAGUGCCUUGGAU

exon_4

ATCTATTAAAACC

CUAUUAAAACC

BCL11A_
−
CTTG
775
GATCTATTAAAACCACA
2086
GAUCUAUUAAAACCACAUC

exon 4

TCGATGGTTCTTT

GAUGGUUCUUU

BCL11A_
−
ATTA
776
AAACCACATCGATGGTT
2087
AAACCACAUCGAUGGUUCU

exon_4

CTTTCTACTTGTT

UUCUACUUGUU

BCL11A_
−
GTTC
777
TTTCTACTTGTTATAAA
2088
UUUCUACUUGUUAUAAACU

exon_4

CTTGTAGCTTAAT

UGUAGCUUAAU

BCL11A_
−
CTTT
778
CTACTTGTTATAAACTT
2089
CUACUUGUUAUAAACUUGU

exon_4

GTAGCTTAATTCA

AGCUUAAUUCA

BCL11A_
−
TTTC
779
TACTTGTTATAAACTTG
2090
UACUUGUUAUAAACUUGUA

exon_4

TAGCTTAATTCAG

GCUUAAUUCAG

BCL11A_
−
ATTG
780
ACAAATTAACAGAAAAA
2091
ACAAAUUAACAGAAAAACA

exon_4

CAGAACAAGTTTA

GAACAAGUUUA

BCL11A_
−
CTTG
781
TTATAAACTTGTAGCTT
2092
UUAUAAACUUGUAGCUUAA

exon_4

AATTCAGCATTGG

UUCAGCAUUGG

BCL11A_
−
CTTG
782
TAGCTTAATTCAGCATT
2093
UAGCUUAAUUCAGCAUUGG

exon 4

GGGTGAGGTAATA

GUGAGGUAAUA

BCL11A_
−
CTTA
783
ATTCAGCATTGGGTGAG
2094
AUUCAGCAUUGGGUGAGGU

exon 4

GTAATAAACCTTA

AAUAAACCUUA

BCL11A_
−
ATTC
784
AGCATTGGGTGAGGTAA
2095
AGCAUUGGGUGAGGUAAUA

exon_4

TAAACCTTAGGAA

AACCUUAGGAA

BCL11A_
−
ATTG
785
GGTGAGGTAATAAACCT
2096
GGUGAGGUAAUAAACCUUA

exon_4

TAGGAACTAGCAT

GGAACUAGCAU

BCL11A_
−
CTTA
786
GGAACTAGCATATAATT
2097
GGAACUAGCAUAUAAUUCU

exon_4

CTATATTGTATTT

AUAUUGUAUUU

BCL11A_
−
ATTC
787
TATATTGTATTTCTCAC
2098
UAUAUUGUAUUUCUCACAA

exon_4

AACAATGGCTACC

CAAUGGCUACC

BCL11A_
−
ATTG
788
TATTTCTCACAACAATG
2099
UAUUUCUCACAACAAUGGC

exon_4

GCTACCTAAAAAG

UACCUAAAAAG

BCL11A_
−
ATTT
789
CTCACAACAATGGCTAC
2100
CUCACAACAAUGGCUACCU

exon_4

CTAAAAAGATGAC

AAAAAGAUGAC

BCL11A_
−
TTTC
790
TCACAACAATGGCTACC
2101
UCACAACAAUGGCUACCUA

exon_4

TAAAAAGATGACC

AAAAGAUGACC

BCL11A_
−
ATTA
791
TGTCCTAGTTAATCATC
2102
UGUCCUAGUUAAUCAUCAU

exon_4

ATTTTTCCTTTAG

UUUUCCUUUAG

BCL11A_
−
GTTA
792
ATCATCATTTTTCCTTT
2103
AUCAUCAUUUUUCCUUUAG

exon_4

AGTTTAATTTTAT

UUUAAUUUUAU

BCL11A_
−
ATTT
793
TTCCTTTAGTTTAATTT
2104
UUCCUUUAGUUUAAUUUUA

exon_4

TATAAACAAAACT

UAAACAAAACU

BCL11A_
−
TTTT
794
TCCTTTAGTTTAATTTT
2105
UCCUUUAGUUUAAUUUUAU

exon_4

ATAAACAAAACTG

AAACAAAACUG

BCL11A_
−
TTTT
795
CCTTTAGTTTAATTTTA
2106
CCUUUAGUUUAAUUUUAUA

exon_4

TAAACAAAACTGA

AACAAAACUGA

BCL11A_
−
GTTA
796
TAAACTTGTAGCTTAAT
2107
UAAACUUGUAGCUUAAUUC

exon_4

TCAGCATTGGGTG

AGCAUUGGGUG

BCL11A_
−
CTTG
797
AATTGACAAATTAACAG
2108
AAUUGACAAAUUAACAGAA

exon_4

AAAAACAGAACAA

AAACAGAACAA

BCL11A_
−
ATTG
798
GAAAGGAAGAAAAAAGG
2109
GAAAGGAAGAAAAAAGGCC

exon_4

CCTTGAATTGACA

UUGAAUUGACA

BCL11A_
−
GTTA
799
AATGTATCAATTGGAAA
2110
AAUGUAUCAAUUGGAAAGG

exon_4

GGAAGAAAAAAGG

AAGAAAAAAGG

BCL11A_
−
GTTT
800
TTTTTTAAACTTAGACA
2111
UUUUUUAAACUUAGACAGC

exon_4

GCATGTATGGTAT

AUGUAUGGUAU

BCL11A_
−
TTTT
801
TTTTTAAACTTAGACAG
2112
UUUUUAAACUUAGACAGCA

exon_4

CATGTATGGTATG

UGUAUGGUAUG

BCL11A_
−
TTTT
802
TTTTAAACTTAGACAGC
2113
UUUUAAACUUAGACAGCAU

exon_4

ATGTATGGTATGT

GUAUGGUAUGU

BCL11A_
−
TTTT
803
TTTAAACTTAGACAGCA
2114
UUUAAACUUAGACAGCAUG

exon_4

TGTATGGTATGTT

UAUGGUAUGUU

BCL11A_
−
TTTT
804
TTAAACTTAGACAGCAT
2115
UUAAACUUAGACAGCAUGU

exon_4

GTATGGTATGTTA

AUGGUAUGUUA

BCL11A_
−
TTTT
805
TAAACTTAGACAGCATG
2116
UAAACUUAGACAGCAUGUA

exon_4

TATGGTATGTTAT

UGGUAUGUUAU

BCL11A_
−
TTTT
806
AAACTTAGACAGCATGT
2117
AAACUUAGACAGCAUGUAU

exon_4

ATGGTATGTTATG

GGUAUGUUAUG

BCL11A_
−
TTTA
807
AACTTAGACAGCATGTA
2118
AACUUAGACAGCAUGUAUG

exon 4

TGGTATGTTATGG

GUAUGUUAUGG

BCL11A_
−
CTTA
808
GACAGCATGTATGGTAT
2119
GACAGCAUGUAUGGUAUGU

exon_4

GTTATGGCTATTT

UAUGGCUAUUU

BCL11A_
−
GTTA
809
TGGCTATTTTAAATTGT
2120
UGGCUAUUUUAAAUUGUCC

exon_4

CCCTAATTCGTTG

CUAAUUCGUUG

BCL11A_
−
ATTT
810
TAAATTGTCCCTAATTC
2121
UAAAUUGUCCCUAAUUCGU

exon_4

GTTGCTGAGCAAA

UGCUGAGCAAA

BCL11A_
−
TTTT
811
AAATTGTCCCTAATTCG
2122
AAAUUGUCCCUAAUUCGUU

exon 4

TTGCTGAGCAAAC

GCUGAGCAAAC

BCL11A_
−
TTTA
812
AATTGTCCCTAATTCGT
2123
AAUUGUCCCUAAUUCGUUG

exon 4

TGCTGAGCAAACA

CUGAGCAAACA

BCL11A_
−
ATTG
813
TCCCTAATTCGTTGCTG
2124
UCCCUAAUUCGUUGCUGAG

exon_4

AGCAAACATGTTG

CAAACAUGUUG

BCL11A_
−
ATTC
814
GTTGCTGAGCAAACATG
2125
GUUGCUGAGCAAACAUGUU

exon_4

TTGCTGTTTCCAG

GCUGUUUCCAG

BCL11A_
−
GTTG
815
CTGAGCAAACATGTTGC
2126
CUGAGCAAACAUGUUGCUG

exon_4

TGTTTCCAGTTCC

UUUCCAGUUCC

BCL11A_
−
GTTG
816
CTGTTTCCAGTTCCGTT
2127
CUGUUUCCAGUUCCGUUCU

exon_4

CTGAGAGAAAAAG

GAGAGAAAAAG

BCL11A_
−
ATTA
817
ACCCTCTATAGACAGAA
2128
ACCCUCUAUAGACAGAAUA

exon_4

TAGATAGCACTGA

GAUAGCACUGA

BCL11A_
−
TTTG
818
GATTAACCCTCTATAGA
2129
GAUUAACCCUCUAUAGACA

exon 4

CAGAATAGATAGC

GAAUAGAUAGC

BCL11A_
−
CTTT
819
GGATTAACCCTCTATAG
2130
GGAUUAACCCUCUAUAGAC

exon 4

ACAGAATAGATAG

AGAAUAGAUAG

BCL11A_
−
TTTA
820
TAACGTGAGGAGGAAAA
2131
UAACGUGAGGAGGAAAAAC

exon 4

ACAGTCTTTGGAT

AGUCUUUGGAU

BCL11A_
−
TTTT
821
ATAACGTGAGGAGGAAA
2132
AUAACGUGAGGAGGAAAAA

exon_4

AACAGTCTTTGGA

CAGUCUUUGGA

BCL11A_
−
ATTT
822
TATAACGTGAGGAGGAA
2133
UAUAACGUGAGGAGGAAAA

exon_4

AAACAGTCTTTGG

ACAGUCUUUGG

BCL11A_
−
TTTC
823
CTTTAGTTTAATTTTAT
2134
CUUUAGUUUAAUUUUAUAA

exon 4

AAACAAAACTGAT

ACAAAACUGAU

BCL11A_
−
TTTA
824
TTTTATAACGTGAGGAG
2135
UUUUAUAACGUGAGGAGGA

exon 4

GAAAAACAGTCTT

AAAACAGUCUU

BCL11A_
−
GTTT
825
TATTTTATAACGTGAGG
2136
UAUUUUAUAACGUGAGGAG

exon_4

AGGAAAAACAGTC

GAAAAACAGUC

BCL11A_
−
ATTC
826
TGTAATACATATCATGT
2137
UGUAAUACAUAUCAUGUAC

exon_4

ACAGTTTTATTTT

AGUUUUAUUUU

BCL11A_
−
GTTC
827
TGAGAGAAAAAGAGAGA
2138
UGAGAGAAAAAGAGAGAGA

exon_4

GAGAGAGAAAAAG

GAGAGAAAAAG

BCL11A_
−
GTTC
828
CGTTCTGAGAGAAAAAG
2139
CGUUCUGAGAGAAAAAGAG

exon_4

AGAGAGAGAGAGA

AGAGAGAGAGA

BCL11A_
−
TTTC
829
CAGTTCCGTTCTGAGAG
2140
CAGUUCCGUUCUGAGAGAA

exon_4

AAAAAGAGAGAGA

AAAGAGAGAGA

BCL11A_
−
GTTT
830
CCAGTTCCGTTCTGAGA
2141
CCAGUUCCGUUCUGAGAGA

exon_4

GAAAAAGAGAGAG

AAAAGAGAGAG

BCL11A_
−
TTTT
831
ATTTTATAACGTGAGGA
2142
AUUUUAUAACGUGAGGAGG

exon_4

GGAAAAACAGTCT

AAAAACAGUCU

BCL11A_
−
CTTT
832
AGTTTAATTTTATAAAC
2143
AGUUUAAUUUUAUAAACAA

exon_4

AAAACTGATTATA

AACUGAUUAUA

BCL11A_
−
TTTA
833
GTTTAATTTTATAAACA
2144
GUUUAAUUUUAUAAACAAA

exon_4

AAACTGATTATAC

ACUGAUUAUAC

BCL11A_
−
GTTT
834
AATTTTATAAACAAAAC
2145
AAUUUUAUAAACAAAACUG

exon_4

TGATTATACCAGT

AUUAUACCAGU

BCL11A_
−
TTTA
835
AAAATACTGGCACCAAA
2146
AAAAUACUGGCACCAAAAG

exon_4

AGAAATAGATCCA

AAAUAGAUCCA

BCL11A_
−
CTTG
836
GTTGTCAAGTGGACAAT
2147
GUUGUCAAGUGGACAAUCA

exon_4

CAAATGATAAACT

AAUGAUAAACU

BCL11A_
−
GTTG
837
TCAAGTGGACAATCAAA
2148
UCAAGUGGACAAUCAAAUG

exon_4

TGATAAACTTTAA

AUAAACUUUAA

BCL11A_
−
CTTT
838
AAGACCTTGTATACCAT
2149
AAGACCUUGUAUACCAUAU

exon_4

ATTGAAAGGAAGA

UGAAAGGAAGA

BCL11A_
−
TTTA
839
AGACCTTGTATACCATA
2150
AGACCUUGUAUACCAUAUU

exon_4

TTGAAAGGAAGAG

GAAAGGAAGAG

BCL11A_
−
CTTG
840
TATACCATATTGAAAGG
2151
UAUACCAUAUUGAAAGGAA

exon_4

AAGAGGCTGACAA

GAGGCUGACAA

BCL11A_
−
ATTG
841
AAAGGAAGAGGCTGACA
2152
AAAGGAAGAGGCUGACAAU

exon 4

ATAAGGTTTGACA

AAGGUUUGACA

BCL11A_
−
GTTT
842
GACAGAGGGGAACAGAA
2153
GACAGAGGGGAACAGAAGA

exon_4

GAAAATAATATGA

AAAUAAUAUGA

BCL11A_
−
TTTG
843
ACAGAGGGGAACAGAAG
2154
ACAGAGGGGAACAGAAGAA

exon_4

AAAATAATATGAT

AAUAAUAUGAU

BCL11A_
−
ATTT
844
ATTAGCACAACGTGGTA
2155
AUUAGCACAACGUGGUACU

exon 4

CTATTTGCCATTT

AUUUGCCAUUU

BCL11A_
−
TTTA
845
TTAGCACAACGTGGTAC
2156
UUAGCACAACGUGGUACUA

exon 4

TATTTGCCATTTA

UUUGCCAUUUA

BCL11A_
−
ATTA
846
GCACAACGTGGTACTAT
2157
GCACAACGUGGUACUAUUU

exon 4

TTGCCATTTAAAA

GCCAUUUAAAA

BCL11A_
−
ATTT
847
GCCATTTAAAACTAGAA
2158
GCCAUUUAAAACUAGAACA

exon 4

CAGGTATATAAGC

GGUAUAUAAGC

BCL11A_
−
TTTG
848
CCATTTAAAACTAGAAC
2159
CCAUUUAAAACUAGAACAG

exon 4

AGGTATATAAGCT

GUAUAUAAGCU

BCL11A_
−
ATTT
849
AAAACTAGAACAGGTAT
2160
AAAACUAGAACAGGUAUAU

exon 4

ATAAGCTAATATT

AAGCUAAUAUU

BCL11A_
−
TTTA
850
AAACTAGAACAGGTATA
2161
AAACUAGAACAGGUAUAUA

exon 4

TAAGCTAATATTG

AGCUAAUAUUG

BCL11A_
−
ATTG
851
ATACAATGATGATTAAC
2162
AUACAAUGAUGAUUAACUA

exon 4

TATGAATTCTTAA

UGAAUUCUUAA

BCL11A_
−
ATTT
852
CTTTTCCATACACTGTG
2163
CUUUUCCAUACACUGUGUG

exon_4

TGCTATTTGTGTT

CUAUUUGUGUU

BCL11A_
−
CTTC
853
ATTTCTTTTCCATACAC
2164
AUUUCUUUUCCAUACACUG

exon_4

TGTGTGCTATTTG

UGUGCUAUUUG

BCL11A_
−
GTTG
854
TACTTCATTTCTTTTCC
2165
UACUUCAUUUCUUUUCCAU

exon_4

ATACACTGTGTGC

ACACUGUGUGC

BCL11A_
−
TTTA
855
AGAGTAGCAGTATATAT
2166
AGAGUAGCAGUAUAUAUGU

exon_4

GTCTGTGCTCCCT

CUGUGCUCCCU

BCL11A_
−
TTTT
856
AAGAGTAGCAGTATATA
2167
AAGAGUAGCAGUAUAUAUG

exon_4

TGTCTGTGCTCCC

UCUGUGCUCCC

BCL11A_
−
ATTT
857
TAAGAGTAGCAGTATAT
2168
UAAGAGUAGCAGUAUAUAU

exon_4

ATGTCTGTGCTCC

GUCUGUGCUCC

BCL11A_
−
TTTT
858
AAAAATACTGGCACCAA
2169
AAAAAUACUGGCACCAAAA

exon_4

AAGAAATAGATCC

GAAAUAGAUCC

BCL11A_
−
CTTA
859
AAAAAAGAAGAGAAAGA
2170
AAAAAAGAAGAGAAAGAAU

exon_4

ATTTTAAGAGTAG

UUUAAGAGUAG

BCL11A_
−
TTTA
860
AATGTGACATTCTTAAA
2171
AAUGUGACAUUCUUAAAAA

exon 4

AAAAGAAGAGAAA

AAGAAGAGAAA

BCL11A_
−
ATTT
861
AAATGTGACATTCTTAA
2172
AAAUGUGACAUUCUUAAAA

exon_4

AAAAAGAAGAGAA

AAAGAAGAGAA

BCL11A_
−
CTTG
862
CATTTAAATGTGACATT
2173
CAUUUAAAUGUGACAUUCU

exon 4

CTTAAAAAAAGAA

UAAAAAAAGAA

BCL11A_
−
CTTA
863
AGACTTGCATTTAAATG
2174
AGACUUGCAUUUAAAUGUG

exon_4

TGACATTCTTAAA

ACAUUCUUAAA

BCL11A_
−
ATTC
864
TTAAGACTTGCATTTAA
2175
UUAAGACUUGCAUUUAAAU

exon_4

ATGTGACATTCTT

GUGACAUUCUU

BCL11A_
−
ATTA
865
ACTATGAATTCTTAAGA
2176
ACUAUGAAUUCUUAAGACU

exon_4

CTTGCATTTAAAT

UGCAUUUAAAU

BCL11A_
−
ATTC
866
TTAAAAAAAGAAGAGAA
2177
UUAAAAAAAGAAGAGAAAG

exon_4

AGAATTTTAAGAG

AAUUUUAAGAG

BCL11A_
−
GTTG
867
TGTATGTTTTTTTTTAA
2178
UGUAUGUUUUUUUUUAAAC

exon_4

ACTTAGACAGCAT

UUAGACAGCAU

BCL11A_
−
TTTT
868
TAAAAATACTGGCACCA
2179
UAAAAAUACUGGCACCAAA

exon_4

AAAGAAATAGATC

AGAAAUAGAUC

BCL11A_
−
TTTA
869
ATAATGTCTTTTTAAAA
2180
AUAAUGUCUUUUUAAAAAU

exon_4

ATACTGGCACCAA

ACUGGCACCAA

BCL11A_
−
TTTA
870
ATTTTATAAACAAAACT
2181
AUUUUAUAAACAAAACUGA

exon 4

GATTATACCAGTA

UUAUACCAGUA

BCL11A_
−
ATTT
871
TATAAACAAAACTGATT
2182
UAUAAACAAAACUGAUUAU

exon_4

ATACCAGTATAAA

ACCAGUAUAAA

BCL11A_
−
TTTT
872
ATAAACAAAACTGATTA
2183
AUAAACAAAACUGAUUAUA

exon_4

TACCAGTATAAAA

CCAGUAUAAAA

BCL11A_
−
TTTA
873
TAAACAAAACTGATTAT
2184
UAAACAAAACUGAUUAUAC

exon_4

ACCAGTATAAAAG

CAGUAUAAAAG

BCL11A_
−
ATTA
874
TACCAGTATAAAAGCTA
2185
UACCAGUAUAAAAGCUACU

exon_4

CTTTGCTCCTGGT

UUGCUCCUGGU

BCL11A_
−
CTTT
875
GCTCCTGGTGAGAGCTT
2186
GCUCCUGGUGAGAGCUUAA

exon_4

AAAAGAAATGGGC

AAGAAAUGGGC

BCL11A_
−
TTTG
876
CTCCTGGTGAGAGCTTA
2187
CUCCUGGUGAGAGCUUAAA

exon_4

AAAGAAATGGGCT

AGAAAUGGGCU

BCL11A_
−
CTTA
877
AAAGAAATGGGCTGTTT
2188
AAAGAAAUGGGCUGUUUUG

exon_4

TGCCCAAAGTTTT

CCCAAAGUUUU

BCL11A_
−
GTTT
878
TGCCCAAAGTTTTATTT
2189
UGCCCAAAGUUUUAUUUUU

exon_4

TTTTTAAACAATG

UUUAAACAAUG

BCL11A_
−
TTTT
879
GCCCAAAGTTTTATTTT
2190
GCCCAAAGUUUUAUUUUUU

exon_4

TTTTAAACAATGA

UUAAACAAUGA

BCL11A_
−
TTTG
880
CCCAAAGTTTTATTTTT
2191
CCCAAAGUUUUAUUUUUUU

exon_4

TTTAAACAATGAT

UAAACAAUGAU

BCL11A_
−
GTTT
881
TATTTTTTTTAAACAAT
2192
UAUUUUUUUUAAACAAUGA

exon_4

GATTAAATTGAAT

UUAAAUUGAAU

BCL11A_
−
TTTT
882
ATTTTTTTTAAACAATG
2193
AUUUUUUUUAAACAAUGAU

exon_4

ATTAAATTGAATG

UAAAUUGAAUG

BCL11A_
−
TTTA
883
TTTTTTTTAAACAATGA
2194
UUUUUUUUAAACAAUGAUU

exon_4

TTAAATTGAATGT

AAAUUGAAUGU

BCL11A_
−
ATTT
884
TTTTTAAACAATGATTA
2195
UUUUUAAACAAUGAUUAAA

exon 4

AATTGAATGTGTA

UUGAAUGUGUA

BCL11A_
−
TTTT
885
TTTTAAACAATGATTAA
2196
UUUUAAACAAUGAUUAAAU

exon_4

ATTGAATGTGTAA

UGAAUGUGUAA

BCL11A_
−
TTTT
886
TTTAAACAATGATTAAA
2197
UUUAAACAAUGAUUAAAUU

exon_4

TTGAATGTGTAAT

GAAUGUGUAAU

BCL11A_
−
CTTT
887
AATAATGTCTTTTTAAA
2198
AAUAAUGUCUUUUUAAAAA

exon_4

AATACTGGCACCA

UACUGGCACCA

BCL11A_
−
TTTG
888
CTTTAATAATGTCTTTT
2199
CUUUAAUAAUGUCUUUUUA

exon 4

TAAAAATACTGGC

AAAAUACUGGC

BCL11A_
−
ATTT
889
GCTTTAATAATGTCTTT
2200
GCUUUAAUAAUGUCUUUUU

exon 4

TTAAAAATACTGG

AAAAAUACUGG

BCL11A_
−
TTTA
890
TGAAGATATTTGCTTTA
2201
UGAAGAUAUUUGCUUUAAU

exon_4

ATAATGTCTTTTT

AAUGUCUUUUU

BCL11A_
−
TTTT
891
ATGAAGATATTTGCTTT
2202
AUGAAGAUAUUUGCUUUAA

exon_4

AATAATGTCTTTT

UAAUGUCUUUU

BCL11A_
−
ATTT
892
TATGAAGATATTTGCTT
2203
UAUGAAGAUAUUUGCUUUA

exon_4

TAATAATGTCTTT

AUAAUGUCUUU

BCL11A_
−
CTTT
893
TTAAAAATACTGGCACC
2204
UUAAAAAUACUGGCACCAA

exon_4

AAAAGAAATAGAT

AAGAAAUAGAU

BCL11A_
−
GTTC
894
ATTTTATGAAGATATTT
2205
AUUUUAUGAAGAUAUUUGC

exon_4

GCTTTAATAATGT

UUUAAUAAUGU

BCL11A_
−
ATTG
895
AATGTGTAATGTGCAAA
2206
AAUGUGUAAUGUGCAAAAG

exon_4

AGCCCTGGAACGC

CCCUGGAACGC

BCL11A_
−
ATTA
896
AATTGAATGTGTAATGT
2207
AAUUGAAUGUGUAAUGUGC

exon_4

GCAAAAGCCCTGG

AAAAGCCCUGG

BCL11A_
−
TTTA
897
AACAATGATTAAATTGA
2208
AACAAUGAUUAAAUUGAAU

exon_4

ATGTGTAATGTGC

GUGUAAUGUGC

BCL11A_
−
TTTT
898
AAACAATGATTAAATTG
2209
AAACAAUGAUUAAAUUGAA

exon_4

AATGTGTAATGTG

UGUGUAAUGUG

BCL11A_
−
TTTT
899
TAAACAATGATTAAATT
2210
UAAACAAUGAUUAAAUUGA

exon 4

GAATGTGTAATGT

AUGUGUAAUGU

BCL11A_
−
TTTT
900
TTAAACAATGATTAAAT
2211
UUAAACAAUGAUUAAAUUG

exon 4

TGAATGTGTAATG

AAUGUGUAAUG

BCL11A_
−
ATTA
901
AATACACTAGTAAGGAG
2212
AAUACACUAGUAAGGAGUU

exon_4

TTCATTTTATGAA

CAUUUUAUGAA

BCL11A_
−
TTTA
902
CATGTTGTGTATGTTTT
2213
CAUGUUGUGUAUGUUUUUU

exon_4

TTTTTAAACTTAG

UUUAAACUUAG

BCL11A_
−
ATTT
903
ACATGTTGTGTATGTTT
2214
ACAUGUUGUGUAUGUUUUU

exon_4

TTTTTTAAACTTA

UUUUAAACUUA

BCL11A_
−
CTTG
904
TGCAATAATTTACATGT
2215
UGCAAUAAUUUACAUGUUG

exon_4

TGTGTATGTTTTT

UGUAUGUUUUU

BCL11A_
−
ATTC
905
CAGCCAGGTAGCAAGCC
2216
CAGCCAGGUAGCAAGCCGC

exon_4

GCCCTTCCTGGCG

CCUUCCUGGCG

BCL11A_
−
CTTC
906
CTGGCGACGCCCCCCCT
2217
CUGGCGACGCCCCCCCUCC

exon_4

CCCTCCTCTGCAA

CUCCUCUGCAA

BCL11A_
−
GTTC
907
TGCGGCAAGACGTTCAA
2218
UGCGGCAAGACGUUCAAAU

exon_4

ATTTCAGAGCAAC

UUCAGAGCAAC

BCL11A_
−
GTTC
908
AAATTTCAGAGCAACCT
2219
AAAUUUCAGAGCAACCUGG

exon_4

GGTGGTGCACCGG

UGGUGCACCGG

BCL11A_
−
ATTT
909
CAGAGCAACCTGGTGGT
2220
CAGAGCAACCUGGUGGUGC

exon_4

GCACCGGCGCAGC

ACCGGCGCAGC

BCL11A_
−
TTTC
910
AGAGCAACCTGGTGGTG
2221
AGAGCAACCUGGUGGUGCA

exon_4

CACCGGCGCAGCC

CCGGCGCAGCC

BCL11A_
−
CTTG
911
GTGGGCAGCGCCAGCAG
2222
GUGGGCAGCGCCAGCAGCG

exon_4

CGCGCTCAAGTCC

CGCUCAAGUCC

BCL11A_
−
GTTC
912
AAGAGCGAGAACGACCC
2223
AAGAGCGAGAACGACCCCA

exon_4

CAACCTGATCCCG

ACCUGAUCCCG

BCL11A_
−
CTTC
913
GGGCTGAGCCTGGAGGC
2224
GGGCUGAGCCUGGAGGCGG

exon_4

GGCGCGCCACCAC

CGCGCCACCAC

BCL11A_
−
CTTC
914
AGCGAGGCCTTCCACCA
2225
AGCGAGGCCUUCCACCAGG

exon_4

GGTCCTGGGCGAG

UCCUGGGCGAG

BCL11A_
−
CTTC
915
CACCAGGTCCTGGGCGA
2226
CACCAGGUCCUGGGCGAGA

exon_4

GAAGCATAAGCGC

AGCAUAAGCGC

BCL11A_
−
CTTG
916
CGACGAAGACTCGGTGG
2227
CGACGAAGACUCGGUGGCC

exon_4

CCGGCGAGTCGGA

GGCGAGUCGGA

BCL11A_
−
GTTA
917
ATGGCCGCGGCTGCTCC
2228
AUGGCCGCGGCUGCUCCCC

exon_4

CCGGGCGAGTCGG

GGGCGAGUCGG

BCL11A_
−
CTTC
918
TCTAAGCGCATCAAGCT
2229
UCUAAGCGCAUCAAGCUCG

exon_4

CGAGAAGGAGTTC

AGAAGGAGUUC

BCL11A_
−
GTTC
919
GACCTGCCCCCGGCCGC
2230
GACCUGCCCCCGGCCGCGA

exon_4

GATGCCCAACACG

UGCCCAACACG

BCL11A_
−
CTTC
920
CTTAGCTTCGGAGACTC
2231
CUUAGCUUCGGAGACUCCA

exon_4

CAGACAATCGCCT

GACAAUCGCCU

BCL11A_
−
CTTA
921
GCTTCGGAGACTCCAGA
2232
GCUUCGGAGACUCCAGACA

exon 4

CAATCGCCTTTTG

AUCGCCUUUUG

BCL11A_
−
ATTT
922
GTAAGATGCCTTTTAGC
2233
GUAAGAUGCCUUUUAGCGU

exon_4

GTGTACAGTACCC

GUACAGUACCC

BCL11A_
−
TTTA
923
CAAATGTGAAATTTGTA
2234
CAAAUGUGAAAUUUGUAAG

exon 4

AGATGCCTTTTAG

AUGCCUUUUAG

BCL11A_
−
GTTT
924
ACAAATGTGAAATTTGT
2235
ACAAAUGUGAAAUUUGUAA

exon_4

AAGATGCCTTTTA

GAUGCCUUUUA

BCL11A_
−
CTTA
925
TAAATGCGAGCTGTGCA
2236
UAAAUGCGAGCUGUGCAAC

exon 4

ACTATGCCTGTGC

UAUGCCUGUGC

BCL11A_
−
CTTC
926
AAGAACTGTAGCAATCT
2237
AAGAACUGUAGCAAUCUCA

exon_4

CACTGTCCACAGG

CUGUCCACAGG

BCL11A_
−
CTTG
927
TGAGTACTGTGGGAAAG
2238
UGAGUACUGUGGGAAAGUC

exon 4

TCTTCAAGAACTG

UUCAAGAACUG

BCL11A_
−
GTTA
928
CTGCAACCATTCCAGCC
2239
CUGCAACCAUUCCAGCCAG

exon 4

AGGTAGCAAGCCG

GUAGCAAGCCG

BCL11A_
−
ATTA
929
GTGGTCCGGGCCCGGGC
2240
GUGGUCCGGGCCCGGGCAG

exon_4

AGGCCCAGCTCAA

GCCCAGCUCAA

BCL11A_
−
TTTG
930
CGCTTCTCCACACCGCC
2241
CGCUUCUCCACACCGCCCG

exon_4

CGGGGAGCTGGAC

GGGAGCUGGAC

BCL11A_
−
GTTT
931
GCGCTTCTCCACACCGC
2242
GCGCUUCUCCACACCGCCC

exon_4

CCGGGGAGCTGGA

GGGGAGCUGGA

BCL11A_
−
TTTG
932
CCTCCTCGTCGGAGCAC
2243
CCUCCUCGUCGGAGCACUC

exon_4

TCCTCGGAGAACG

CUCGGAGAACG

BCL11A_
−
TTTT
933
GCCTCCTCGTCGGAGCA
2244
GCCUCCUCGUCGGAGCACU

exon_4

CTCCTCGGAGAAC

CCUCGGAGAAC

BCL11A_
−
CTTT
934
TGCCTCCTCGTCGGAGC
2245
UGCCUCCUCGUCGGAGCAC

exon_4

ACTCCTCGGAGAA

UCCUCGGAGAA

BCL11A_
−
CTTC
935
GGAGACTCCAGACAATC
2246
GGAGACUCCAGACAAUCGC

exon_4

GCCTTTTGCCTCC

CUUUUGCCUCC

BCL11A_
−
CTTC
936
TCCACACCGCCCGGGGA
2247
UCCACACCGCCCGGGGAGC

exon 4

GCTGGACGGAGGG

UGGACGGAGGG

BCL11A_
−
TTTG
937
TAAGATGCCTTTTAGCG
2248
UAAGAUGCCUUUUAGCGUG

exon_4

TGTACAGTACCCT

UACAGUACCCU

BCL11A_
−
CTTA
938
GAGAGCTGGCAGGGAAC
2249
GAGAGCUGGCAGGGAACAC

exon_4

ACGTCTAGCCCAC

GUCUAGCCCAC

BCL11A_
−
ATTT
939
CTCTAGGAGACTTAGAG
2250
CUCUAGGAGACUUAGAGAG

exon_4

AGCTGGCAGGGAA

CUGGCAGGGAA

BCL11A_
−
ATTA
940
AACATTGATGTTGGTGT
2251
AACAUUGAUGUUGGUGUUG

exon 4

TGTATTATTTTGC

UAUUAUUUUGC

BCL11A_
−
ATTG
941
ATGTTGGTGTTGTATTA
2252
AUGUUGGUGUUGUAUUAUU

exon 4

TTTTGCAGGTAAA

UUGCAGGUAAA

BCL11A_
−
GTTG
942
GTGTTGTATTATTTTGC
2253
GUGUUGUAUUAUUUUGCAG

exon_4

AGGTAAAGATGAG

GUAAAGAUGAG

BCL11A_
−
GTTG
943
TATTATTTTGCAGGTAA
2254
UAUUAUUUUGCAGGUAAAG

exon_4

AGATGAGCCCAGC

AUGAGCCCAGC

BCL11A_
−
ATTA
944
TTTTGCAGGTAAAGATG
2255
UUUUGCAGGUAAAGAUGAG

exon_4

AGCCCAGCAGCTA

CCCAGCAGCUA

BCL11A_
−
ATTT
945
TGCAGGTAAAGATGAGC
2256
UGCAGGUAAAGAUGAGCCC

exon_4

CCAGCAGCTACAC

AGCAGCUACAC

BCL11A_
−
TTTT
946
GCAGGTAAAGATGAGCC
2257
GCAGGUAAAGAUGAGCCCA

exon_4

CAGCAGCTACACA

GCAGCUACACA

BCL11A_
−
TTTG
947
CAGGTAAAGATGAGCCC
2258
CAGGUAAAGAUGAGCCCAG

exon_4

AGCAGCTACACAT

CAGCUACACAU

BCL11A_
−
CTTG
948
CAAACAGCCATTCACCA
2259
CAAACAGCCAUUCACCAGU

exon 4

GTGCATGGTTTCT

GCAUGGUUUCU

BCL11A_
−
ATTC
949
ACCAGTGCATGGTTTCT
2260
ACCAGUGCAUGGUUUCUCU

exon_4

CTTGCAACACGCA

UGCAACACGCA

BCL11A_
−
GTTT
950
CTCTTGCAACACGCACA
2261
CUCUUGCAACACGCACAGA

exon_4

GAACACTCATGGA

ACACUCAUGGA

BCL11A_
−
TTTC
951
TCTTGCAACACGCACAG
2262
UCUUGCAACACGCACAGAA

exon_4

AACACTCATGGAT

CACUCAUGGAU

BCL11A_
−
CTTG
952
CAACACGCACAGAACAC
2263
CAACACGCACAGAACACUC

exon_4

TCATGGATTAAGA

AUGGAUUAAGA

BCL11A_
−
ATTA
953
AGAATCTACTTAGAAAG
2264
AGAAUCUACUUAGAAAGCG

exon_4

CGAACACGGAAGT

AACACGGAAGU

BCL11A_
−
CTTA
954
GAAAGCGAACACGGAAG
2265
GAAAGCGAACACGGAAGUC

exon 4

TCCCCTGACCCCG

CCCUGACCCCG

BCL11A_
−
GTTG
955
GTATCCCTTCAGGACTA
2266
GUAUCCCUUCAGGACUAGG

exon 4

GGTGCAGAATGTC

UGCAGAAUGUC

BCL11A_
−
CTTC
956
AGGACTAGGTGCAGAAT
2267
AGGACUAGGUGCAGAAUGU

exon_4

GTCCTTCCCAGCC

CCUUCCCAGCC

BCL11A_
−
GTTG
957
AATCCAATGGCTATGGA
2268
AAUCCAAUGGCUAUGGAGC

exon_4

GCCTCCCGCCATG

CUCCCGCCAUG

BCL11A_
−
TTTG
958
ACAGGGTGCTGCGGTTG
2269
ACAGGGUGCUGCGGUUGAA

exon_4

AATCCAATGGCTA

UCCAAUGGCUA

BCL11A_
−
CTTT
959
GACAGGGTGCTGCGGTT
2270
GACAGGGUGCUGCGGUUGA

exon_4

GAATCCAATGGCT

AUCCAAUGGCU

BCL11A_
−
CTTG
960
GACCCCCACCGCATAGA
2271
GACCCCCACCGCAUAGAGC

exon_4

GCGCCTGGGGGCG

GCCUGGGGGCG

BCL11A_
−
TTTA
961
GTCCACCACCGAGACAT
2272
GUCCACCACCGAGACAUCA

exon_4

CACTTGGACCCCC

CUUGGACCCCC

BCL11A_
−
GTTT
962
AGTCCACCACCGAGACA
2273
AGUCCACCACCGAGACAUC

exon_4

TCACTTGGACCCC

ACUUGGACCCC

BCL11A_
−
TTTC
963
TCTAGGAGACTTAGAGA
2274
UCUAGGAGACUUAGAGAGC

exon_4

GCTGGCAGGGAAC

UGGCAGGGAAC

BCL11A_
−
TTTC
964
CACCCACTCCCCCCCTG
2275
CACCCACUCCCCCCCUGUU

exon_4

TTTAGTCCACCAC

UAGUCCACCAC

BCL11A_
−
CTTC
965
CGGCCTGGCAGAAGGGC
2276
CGGCCUGGCAGAAGGGCGC

exon_4

GCTTTCCACCCAC

UUUCCACCCAC

BCL11A_
−
TTTA
966
ACCTGCTAAGAATACCA
2277
ACCUGCUAAGAAUACCAGG

exon 4

GGATCAGTATCGA

AUCAGUAUCGA

BCL11A_
−
CTTT
967
AACCTGCTAAGAATACC
2278
AACCUGCUAAGAAUACCAG

exon 4

AGGATCAGTATCG

GAUCAGUAUCG

BCL11A_
−
ATTG
968
CAGACAATAACCCCTTT
2279
CAGACAAUAACCCCUUUAA

exon 4

AACCTGCTAAGAA

CCUGCUAAGAA

BCL11A_
−
ATTC
969
ATATTGCAGACAATAAC
2280
AUAUUGCAGACAAUAACCC

exon 4

CCCTTTAACCTGC

CUUUAACCUGC

BCL11A_
−
CTTC
970
CCAGCCACCTCTCCATG
2281
CCAGCCACCUCUCCAUGGG

exon 4

GGATTCATATTGC

AUUCAUAUUGC

BCL11A_
−
CTTT
971
CCACCCACTCCCCCCCT
2282
CCACCCACUCCCCCCCUGU

exon_4

GTTTAGTCCACCA

UUAGUCCACCA

BCL11A_
−
TTTC
972
TTTTCCATACACTGTGT
2283
UUUUCCAUACACUGUGUGC

exon_4

GCTATTTGTGTTA

UAUUUGUGUUA

BCL11A_
−
CTTT
973
TAGCGTGTACAGTACCC
2284
UAGCGUGUACAGUACCCUG

exon_4

TGGAGAAACACAT

GAGAAACACAU

BCL11A_
−
TTTA
974
GCGTGTACAGTACCCTG
2285
GCGUGUACAGUACCCUGGA

exon_4

GAGAAACACATGA

GAAACACAUGA

BCL11A_
−
TTTC
975
TTTTTCCTTTTTTTTTT
2286
UUUUUCCUUUUUUUUUUUU

exon_4

TTTTCCTTTATGT

UUCCUUUAUGU

BCL11A_
−
CTTT
976
TTCCTTTTTTTTTTTTT
2287
UUCCUUUUUUUUUUUUUUC

exon_4

TCCTTTATGTTCT

CUUUAUGUUCU

BCL11A_
−
TTTT
977
TCCTTTTTTTTTTTTTT
2288
UCCUUUUUUUUUUUUUUCC

exon_4

CCTTTATGTTCTC

UUUAUGUUCUC

BCL11A_
−
TTTT
978
CCTTTTTTTTTTTTTTC
2289
CCUUUUUUUUUUUUUUCCU

exon_4

CTTTATGTTCTCA

UUAUGUUCUCA

BCL11A_
−
TTTC
979
CTTTTTTTTTTTTTTCC
2290
CUUUUUUUUUUUUUUCCUU

exon_4

TTTATGTTCTCAC

UAUGUUCUCAC

BCL11A_
−
CTTT
980
TTTTTTTTTTTCCTTTA
2291
UUUUUUUUUUUCCUUUAUG

exon 4

TGTTCTCACCGTT

UUCUCACCGUU

BCL11A_
−
TTTT
981
TTTTTTTTTTCCTTTAT
2292
UUUUUUUUUUCCUUUAUGU

exon 4

GTTCTCACCGTTT

UCUCACCGUUU

BCL11A_
−
TTTT
982
TTTTTTTTTCCTTTATG
2293
UUUUUUUUUCCUUUAUGUU

exon_4

TTCTCACCGTTTG

CUCACCGUUUG

BCL11A_
−
TTTT
983
TTTTTTTTCCTTTATGT
2294
UUUUUUUUCCUUUAUGUUC

exon 4

TCTCACCGTTTGA

UCACCGUUUGA

BCL11A_
−
TTTT
984
TTTTTTTCCTTTATGTT
2295
UUUUUUUCCUUUAUGUUCU

exon 4

CTCACCGTTTGAA

CACCGUUUGAA

BCL11A_
−
TTTT
985
TTTTTTCCTTTATGTTC
2296
UUUUUUCCUUUAUGUUCUC

exon_4

TCACCGTTTGAAT

ACCGUUUGAAU

BCL11A_
−
TTTT
986
TTTTTCCTTTATGTTCT
2297
UUUUUCCUUUAUGUUCUCA

exon 4

CACCGTTTGAATG

CCGUUUGAAUG

BCL11A_
−
TTTT
987
TTTTCCTTTATGTTCTC
2298
UUUUCCUUUAUGUUCUCAC

exon_4

ACCGTTTGAATGC

CGUUUGAAUGC

BCL11A_
−
TTTT
988
TTTCCTTTATGTTCTCA
2299
UUUCCUUUAUGUUCUCACC

exon_4

CCGTTTGAATGCA

GUUUGAAUGCA

BCL11A_
−
TTTT
989
TTCCTTTATGTTCTCAC
2300
UUCCUUUAUGUUCUCACCG

exon 4

CGTTTGAATGCAT

UUUGAAUGCAU

BCL11A_
−
TTTT
990
TCCTTTATGTTCTCACC
2301
UCCUUUAUGUUCUCACCGU

exon 4

GTTTGAATGCATG

UUGAAUGCAUG

BCL11A_
−
TTTT
991
CCTTTATGTTCTCACCG
2302
CCUUUAUGUUCUCACCGUU

exon_4

TTTGAATGCATGA

UGAAUGCAUGA

BCL11A_
−
TTTC
992
TCTTGTGCAATAATTTA
2303
UCUUGUGCAAUAAUUUACA

exon_4

CATGTTGTGTATG

UGUUGUGUAUG

BCL11A_
−
CTTT
993
CTCTTGTGCAATAATTT
2304
CUCUUGUGCAAUAAUUUAC

exon 4

ACATGTTGTGTAT

AUGUUGUGUAU

BCL11A_
−
TTTG
994
AGCCTTTCTCTTGTGCA
2305
AGCCUUUCUCUUGUGCAAU

exon_4

ATAATTTACATGT

AAUUUACAUGU

BCL11A_
−
CTTT
995
GAGCCTTTCTCTTGTGC
2306
GAGCCUUUCUCUUGUGCAA

exon_4

AATAATTTACATG

UAAUUUACAUG

BCL11A_
−
TTTA
996
CGCAAACTTTGAGCCTT
2307
CGCAAACUUUGAGCCUUUC

exon_4

TCTCTTGTGCAAT

UCUUGUGCAAU

BCL11A_
−
TTTT
997
ACGCAAACTTTGAGCCT
2308
ACGCAAACUUUGAGCCUUU

exon_4

TTCTCTTGTGCAA

CUCUUGUGCAA

BCL11A_
−
TTTT
998
CTTTTTCCTTTTTTTTT
2309
CUUUUUCCUUUUUUUUUUU

exon_4

TTTTTCCTTTATG

UUUCCUUUAUG

BCL11A_
−
ATTT
999
TACGCAAACTTTGAGCC
2310
UACGCAAACUUUGAGCCUU

exon_4

TTTCTCTTGTGCA

UCUCUUGUGCA

BCL11A_
−
TTTG
1000
AATGCATGATCTGTATG
2311
AAUGCAUGAUCUGUAUGGG

exon_4

GGGCAATACTATT

GCAAUACUAUU

BCL11A_
−
GTTT
1001
GAATGCATGATCTGTAT
2312
GAAUGCAUGAUCUGUAUGG

exon_4

GGGGCAATACTAT

GGCAAUACUAU

BCL11A_
−
GTTC
1002
TCACCGTTTGAATGCAT
2313
UCACCGUUUGAAUGCAUGA

exon_4

GATCTGTATGGGG

UCUGUAUGGGG

BCL11A_
−
TTTA
1003
TGTTCTCACCGTTTGAA
2314
UGUUCUCACCGUUUGAAUG

exon_4

TGCATGATCTGTA

CAUGAUCUGUA

BCL11A_
−
CTTT
1004
ATGTTCTCACCGTTTGA
2315
AUGUUCUCACCGUUUGAAU

exon_4

ATGCATGATCTGT

GCAUGAUCUGU

BCL11A_
−
TTTC
1005
CTTTATGTTCTCACCGT
2316
CUUUAUGUUCUCACCGUUU

exon_4

TTGAATGCATGAT

GAAUGCAUGAU

BCL11A_
−
ATTG
1006
CATTTTACGCAAACTTT
2317
CAUUUUACGCAAACUUUGA

exon_4

GAGCCTTTCTCTT

GCCUUUCUCUU

BCL11A_
−
TTTT
1007
AGCGTGTACAGTACCCT
2318
AGCGUGUACAGUACCCUGG

exon_4

GGAGAAACACATG

AGAAACACAUG

BCL11A_
−
TTTT
1008
TCTTTTTCCTTTTTTTT
2319
UCUUUUUCCUUUUUUUUUU

exon_4

TTTTTTCCTTTAT

UUUUCCUUUAU

BCL11A_
−
CTTT
1009
TTTCTTTTTCCTTTTTT
2320
UUUCUUUUUCCUUUUUUUU

exon_4

TTTTTTTTCCTTT

UUUUUUCCUUU

BCL11A_
−
GTTG
1010
AATAATGATATAAAAAC
2321
AAUAAUGAUAUAAAAACUG

exon_4

TGAATAGAGGTAT

AAUAGAGGUAU

BCL11A_
−
ATTA
1011
ATACCCCTCCCTCACTC
2322
AUACCCCUCCCUCACUCCC

exon_4

CCACCTGACACCC

ACCUGACACCC

BCL11A_
−
CTTT
1012
TTCACCACTCCCCTTCC
2323
UUCACCACUCCCCUUCCCC

exon_4

CCATCGCCCTCCA

AUCGCCCUCCA

BCL11A_
−
TTTT
1013
TCACCACTCCCCTTCCC
2324
UCACCACUCCCCUUCCCCA

exon 4

CATCGCCCTCCAG

UCGCCCUCCAG

BCL11A_
−
TTTT
1014
CACCACTCCCCTTCCCC
2325
CACCACUCCCCUUCCCCAU

exon_4

ATCGCCCTCCAGC

CGCCCUCCAGC

BCL11A_
−
TTTC
1015
ACCACTCCCCTTCCCCA
2326
ACCACUCCCCUUCCCCAUC

exon 4

TCGCCCTCCAGCC

GCCCUCCAGCC

BCL11A_
−
CTTC
1016
CCCATCGCCCTCCAGCC
2327
CCCAUCGCCCUCCAGCCCC

exon_4

CCACTCCCTGTAG

ACUCCCUGUAG

BCL11A_
−
ATTT
1017
TTTTCTAGTCCCATGTG
2328
UUUUCUAGUCCCAUGUGAU

exon_4

ATTTAAACAAACA

UUAAACAAACA

BCL11A_
−
TTTT
1018
TTTCTAGTCCCATGTGA
2329
UUUCUAGUCCCAUGUGAUU

exon_4

TTTAAACAAACAA

UAAACAAACAA

BCL11A_
−
TTTT
1019
TTCTAGTCCCATGTGAT
2330
UUCUAGUCCCAUGUGAUUU

exon_4

TTAAACAAACAAA

AAACAAACAAA

BCL11A_
−
TTTT
1020
TCTAGTCCCATGTGATT
2331
UCUAGUCCCAUGUGAUUUA

exon_4

TAAACAAACAAAC

AACAAACAAAC

BCL11A_
−
TTTT
1021
CTAGTCCCATGTGATTT
2332
CUAGUCCCAUGUGAUUUAA

exon_4

AAACAAACAAACA

ACAAACAAACA

BCL11A_
−
TTTC
1022
TAGTCCCATGTGATTTA
2333
UAGUCCCAUGUGAUUUAAA

exon_4

AACAAACAAACAA

CAAACAAACAA

BCL11A_
−
ATTT
1023
AAACAAACAAACAAACA
2334
AAACAAACAAACAAACAAA

exon_4

AACAGAAGTAACG

CAGAAGUAACG

BCL11A_
−
TTTA
1024
AACAAACAAACAAACAA
2335
AACAAACAAACAAACAAAC

exon 4

ACAGAAGTAACGA

AGAAGUAACGA

BCL11A_
−
CTTG
1025
TCACCAGCACACCTGTT
2336
UCACCAGCACACCUGUUUU

exon 4

TTTTTTCTTTTTC

UUUUCUUUUUC

BCL11A_
−
GTTT
1026
TTTTTCTTTTTCTTTTT
2337
UUUUUCUUUUUCUUUUUCU

exon 4

CTTTTTTCTTTTT

UUUUUCUUUUU

BCL11A_
−
TTTC
1027
TTTTTTCTTTTTCCTTT
2338
UUUUUUCUUUUUCCUUUUU

exon_4

TTTTTTTTTTTCC

UUUUUUUUUCC

BCL11A_
−
TTTT
1028
CTTTTTTCTTTTTCCTT
2339
CUUUUUUCUUUUUCCUUUU

exon_4

TTTTTTTTTTTTC

UUUUUUUUUUC

BCL11A_
−
TTTT
1029
TCTTTTTTCTTTTTCCT
2340
UCUUUUUUCUUUUUCCUUU

exon_4

TTTTTTTTTTTTT

UUUUUUUUUUU

BCL11A_
−
CTTT
1030
TTCTTTTTTCTTTTTCC
2341
UUCUUUUUUCUUUUUCCUU

exon_4

TTTTTTTTTTTTT

UUUUUUUUUUU

BCL11A_
−
TTTC
1031
TTTTTCTTTTTTCTTTT
2342
UUUUUCUUUUUUUUUUUC

exon_4

TCCTTTTTTTTTT

CUUUUUUUUUU

BCL11A_
−
TTTT
1032
CTTTTTCTTTTTTCTTT
2343
CUUUUUCUUUUUUCUUUUU

exon_4

TTCCTTTTTTTTT

CCUUUUUUUUU

BCL11A_
−
TTTT
1033
TTCTTTTTCCTTTTTTT
2344
UUCUUUUUCCUUUUUUUUU

exon_4

TTTTTTTCCTTTA

UUUUUCCUUUA

BCL11A_
−
TTTT
1034
TCTTTTTCTTTTTTCTT
2345
UCUUUUUCUUUUUUUUUU

exon_4

TTTCCTTTTTTTT

UCCUUUUUUUU

BCL11A_
−
TTTC
1035
TTTTTCTTTTTCTTTTT
2346
UUUUUCUUUUUCUUUUUUC

exon_4

TCTTTTTCCTTTT

UUUUUCCUUUU

BCL11A_
−
TTTT
1036
CTTTTTCTTTTTCTTTT
2347
CUUUUUCUUUUUCUUUUUU

exon_4

TTCTTTTTCCTTT

CUUUUUCCUUU

BCL11A_
−
TTTT
1037
TCTTTTTCTTTTTCTTT
2348
UCUUUUUCUUUUUCUUUUU

exon_4

TTTCTTTTTCCTT

UCUUUUUCCUU

BCL11A_
−
TTTT
1038
TTCTTTTTCTTTTTCTT
2349
UUCUUUUUCUUUUUCUUUU

exon_4

TTTTCTTTTTCCT

UUCUUUUUCCU

BCL11A_
−
TTTT
1039
TTTCTTTTTCTTTTTCT
2350
UUUCUUUUUCUUUUUCUUU

exon_4

TTTTTCTTTTTCC

UUUCUUUUUCC

BCL11A_
−
TTTT
1040
TTTTCTTTTTCTTTTTC
2351
UUUUCUUUUUCUUUUUCUU

exon 4

TTTTTTCTTTTTC

UUUUCUUUUUC

BCL11A_
−
CTTT
1041
TTCTTTTTCTTTTTTCT
2352
UUCUUUUUCUUUUUUCUUU

exon_4

TTTTCCTTTTTTT

UUCCUUUUUUU

BCL11A_
−
TTTT
1042
TTTGGCAGTTGTCTGCA
2353
UUUGGCAGUUGUCUGCAUU

exon 4

TTAACCTGTTCAT

AACCUGUUCAU

BCL11A_
−
CTTT
1043
TCCATACACTGTGTGCT
2354
UCCAUACACUGUGUGCUAU

exon_4

ATTTGTGTTAACA

UUGUGUUAACA

BCL11A_
−
TTTC
1044
CATACACTGTGTGCTAT
2355
CAUACACUGUGUGCUAUUU

exon 4

TTGTGTTAACATG

GUGUUAACAUG

BCL11A_
−
TTTT
1045
GTCCCTTTCCTTCTATC
2356
GUCCCUUUCCUUCUAUCAC

exon_4

ACCCTACATTCCA

CCUACAUUCCA

BCL11A_
−
TTTG
1046
TCCCTTTCCTTCTATCA
2357
UCCCUUUCCUUCUAUCACC

exon_4

CCCTACATTCCAG

CUACAUUCCAG

BCL11A_
−
CTTT
1047
CCTTCTATCACCCTACA
2358
CCUUCUAUCACCCUACAUU

exon_4

TTCCAGCATCTTA

CCAGCAUCUUA

BCL11A_
+
CTTT
1048
ACCTGCAAAATAATACA
2359
ACCUGCAAAAUAAUACAAC

exon_4

ACACCAACATCAA

ACCAACAUCAA

BCL11A_
−
CTTC
1049
TATCACCCTACATTCCA
2360
UAUCACCCUACAUUCCAGC

exon_4

GCATCTTACCTTC

AUCUUACCUUC

BCL11A_
−
ATTC
1050
CAGCATCTTACCTTCAT
2361
CAGCAUCUUACCUUCAUAU

exon_4

ATGCAGTAAAAGA

GCAGUAAAAGA

BCL11A_
−
CTTA
1051
CCTTCATATGCAGTAAA
2362
CCUUCAUAUGCAGUAAAAG

exon_4

AGAAAGAAAGAAA

AAAGAAAGAAA

BCL11A_
−
CTTC
1052
ATATGCAGTAAAAGAAA
2363
AUAUGCAGUAAAAGAAAGA

exon_4

GAAAGAAAAAAAA

AAGAAAAAAAA

BCL11A_
−
GTTT
1053
TGCAGTTTTTTTCATTG
2364
UGCAGUUUUUUUCAUUGCC

exon_4

CCAAAAACTAAAT

AAAAACUAAAU

BCL11A_
−
TTTT
1054
GCAGTTTTTTTCATTGC
2365
GCAGUUUUUUUCAUUGCCA

exon_4

CAAAAACTAAATG

AAAACUAAAUG

BCL11A_
−
TTTG
1055
CAGTTTTTTTCATTGCC
2366
CAGUUUUUUUCAUUGCCAA

exon_4

AAAAACTAAATGG

AAACUAAAUGG

BCL11A_
−
GTTT
1056
TTTTCATTGCCAAAAAC
2367
UUUUCAUUGCCAAAAACUA

exon_4

TAAATGGTGCTTT

AAUGGUGCUUU

BCL11A_
−
TTTT
1057
TTTCATTGCCAAAAACT
2368
UUUCAUUGCCAAAAACUAA

exon_4

AAATGGTGCTTTA

AUGGUGCUUUA

BCL11A_
−
TTTT
1058
TTCATTGCCAAAAACTA
2369
UUCAUUGCCAAAAACUAAA

exon_4

AATGGTGCTTTAT

UGGUGCUUUAU

BCL11A_
−
TTTT
1059
TGTCCCTTTCCTTCTAT
2370
UGUCCCUUUCCUUCUAUCA

exon_4

CACCCTACATTCC

CCCUACAUUCC

BCL11A_
−
TTTT
1060
TCATTGCCAAAAACTAA
2371
UCAUUGCCAAAAACUAAAU

exon_4

ATGGTGCTTTATA

GGUGCUUUAUA

BCL11A_
−
TTTC
1061
ATTGCCAAAAACTAAAT
2372
AUUGCCAAAAACUAAAUGG

exon_4

GGTGCTTTATATT

UGCUUUAUAUU

BCL11A_
−
ATTG
1062
CCAAAAACTAAATGGTG
2373
CCAAAAACUAAAUGGUGCU

exon_4

CTTTATATTTAGA

UUAUAUUUAGA

BCL11A_
−
CTTT
1063
ATATTTAGATTGGAAAG
2374
AUAUUUAGAUUGGAAAGAA

exon_4

AATTTCATATGCA

UUUCAUAUGCA

BCL11A_
−
TTTA
1064
TATTTAGATTGGAAAGA
2375
UAUUUAGAUUGGAAAGAAU

exon_4

ATTTCATATGCAA

UUCAUAUGCAA

BCL11A_
−
ATTT
1065
AGATTGGAAAGAATTTC
2376
AGAUUGGAAAGAAUUUCAU

exon_4

ATATGCAAAGCAT

AUGCAAAGCAU

BCL11A_
−
TTTA
1066
GATTGGAAAGAATTTCA
2377
GAUUGGAAAGAAUUUCAUA

exon_4

TATGCAAAGCATA

UGCAAAGCAUA

BCL11A_
−
ATTG
1067
GAAAGAATTTCATATGC
2378
GAAAGAAUUUCAUAUGCAA

exon_4

AAAGCATATTAAA

AGCAUAUUAAA

BCL11A_
−
ATTT
1068
CATATGCAAAGCATATT
2379
CAUAUGCAAAGCAUAUUAA

exon_4

AAAGAGAAAGCCC

AGAGAAAGCCC

BCL11A_
−
TTTC
1069
ATATGCAAAGCATATTA
2380
AUAUGCAAAGCAUAUUAAA

exon_4

AAGAGAAAGCCCG

GAGAAAGCCCG

BCL11A_
−
ATTA
1070
AAGAGAAAGCCCGCTTT
2381
AAGAGAAAGCCCGCUUUAG

exon_4

AGTCAATACTTTT

UCAAUACUUUU

BCL11A_
−
CTTT
1071
AGTCAATACTTTTTTGT
2382
AGUCAAUACUUUUUUGUAA

exon_4

AAATGGCAATGCA

AUGGCAAUGCA

BCL11A_
−
TTTA
1072
GTCAATACTTTTTTGTA
2383
GUCAAUACUUUUUUGUAAA

exon_4

AATGGCAATGCAG

UGGCAAUGCAG

BCL11A_
−
CTTT
1073
TTTGTAAATGGCAATGC
2384
UUUGUAAAUGGCAAUGCAG

exon 4

AGAATATTTTGTT

AAUAUUUUGUU

BCL11A_
−
TTTT
1074
TTGTAAATGGCAATGCA
2385
UUGUAAAUGGCAAUGCAGA

exon_4

GAATATTTTGTTA

AUAUUUUGUUA

BCL11A_
−
TTTT
1075
CATTGCCAAAAACTAAA
2386
CAUUGCCAAAAACUAAAUG

exon_4

TGGTGCTTTATAT

GUGCUUUAUAU

BCL11A_
−
CTTT
1076
TTGTCCCTTTCCTTCTA
2387
UUGUCCCUUUCCUUCUAUC

exon_4

TCACCCTACATTC

ACCCUACAUUC

BCL11A_
−
GTTA
1077
TGTAGTGTGCTTTTTGT
2388
UGUAGUGUGCUUUUUGUCC

exon_4

CCCTTTCCTTCTA

CUUUCCUUCUA

BCL11A_
−
TTTG
1078
TTATGTAGTGTGCTTTT
2389
UUAUGUAGUGUGCUUUUUG

exon_4

TGTCCCTTTCCTT

UCCCUUUCCUU

BCL11A_
−
TTTT
1079
TGGTAGTGGAAAAAAAA
2390
UGGUAGUGGAAAAAAAAAA

exon_4

AAGACAGGCTGCC

GACAGGCUGCC

BCL11A_
−
TTTT
1080
GGTAGTGGAAAAAAAAA
2391
GGUAGUGGAAAAAAAAAAG

exon_4

AGACAGGCTGCCA

ACAGGCUGCCA

BCL11A_
−
TTTG
1081
GTAGTGGAAAAAAAAAA
2392
GUAGUGGAAAAAAAAAAGA

exon_4

GACAGGCTGCCAC

CAGGCUGCCAC

BCL11A_
−
ATTT
1082
TTTTAATTTGGCAGGAT
2393
UUUUAAUUUGGCAGGAUAA

exon_4

AATATAGTGCAAA

UAUAGUGCAAA

BCL11A_
−
TTTT
1083
TTTAATTTGGCAGGATA
2394
UUUAAUUUGGCAGGAUAAU

exon_4

ATATAGTGCAAAT

AUAGUGCAAAU

BCL11A_
−
TTTT
1084
TTAATTTGGCAGGATAA
2395
UUAAUUUGGCAGGAUAAUA

exon_4

TATAGTGCAAATT

UAGUGCAAAUU

BCL11A_
−
TTTT
1085
TAATTTGGCAGGATAAT
2396
UAAUUUGGCAGGAUAAUAU

exon_4

ATAGTGCAAATTA

AGUGCAAAUUA

BCL11A_
−
TTTT
1086
AATTTGGCAGGATAATA
2397
AAUUUGGCAGGAUAAUAUA

exon_4

TAGTGCAAATTAT

GUGCAAAUUAU

BCL11A_
−
TTTA
1087
ATTTGGCAGGATAATAT
2398
AUUUGGCAGGAUAAUAUAG

exon_4

AGTGCAAATTATT

UGCAAAUUAUU

BCL11A_
−
ATTT
1088
GGCAGGATAATATAGTG
2399
GGCAGGAUAAUAUAGUGCA

exon_4

CAAATTATTTGTA

AAUUAUUUGUA

BCL11A_
−
TTTG
1089
GCAGGATAATATAGTGC
2400
GCAGGAUAAUAUAGUGCAA

exon_4

AAATTATTTGTAT

AUUAUUUGUAU

BCL11A_
−
ATTA
1090
TTTGTATGCTTCAAAAA
2401
UUUGUAUGCUUCAAAAAAA

exon 4

AAAAAAAAAGAGA

AAAAAAAGAGA

BCL11A_
−
ATTT
1091
GTATGCTTCAAAAAAAA
2402
GUAUGCUUCAAAAAAAAAA

exon 4

AAAAAAGAGAGAA

AAAAGAGAGAA

BCL11A_
−
TTTG
1092
TATGCTTCAAAAAAAAA
2403
UAUGCUUCAAAAAAAAAAA

exon_4

AAAAAGAGAGAAA

AAAGAGAGAAA

BCL11A_
−
CTTC
1093
AAAAAAAAAAAAAAGAG
2404
AAAAAAAAAAAAAAGAGAG

exon_4

AGAAACAAAAAAG

AAACAAAAAAG

BCL11A_
−
ATTA
1094
CAGATGAGAAGCCATAT
2405
CAGAUGAGAAGCCAUAUAA

exon_4

AATGGCGGTTTGG

UGGCGGUUUGG

BCL11A_
−
GTTT
1095
GGGGGAGCCTGCTAGAA
2406
GGGGGAGCCUGCUAGAAUG

exon_4

TGTCACATGGATG

UCACAUGGAUG

BCL11A_
−
GTTT
1096
GTTATGTAGTGTGCTTT
2407
GUUAUGUAGUGUGCUUUUU

exon_4

TTGTCCCTTTCCT

GUCCCUUUCCU

BCL11A_
−
GTTG
1097
GTTTGTTATGTAGTGTG
2408
GUUUGUUAUGUAGUGUGCU

exon_4

CTTTTTGTCCCTT

UUUUGUCCCUU

BCL11A_
−
TTTC
1098
CTGCTGCCATACTGTAT
2409
CUGCUGCCAUACUGUAUGC

exon_4

GCAGTACTGCAAG

AGUACUGCAAG

BCL11A_
−
TTTT
1099
CCTGCTGCCATACTGTA
2410
CCUGCUGCCAUACUGUAUG

exon_4

TGCAGTACTGCAA

CAGUACUGCAA

BCL11A_
−
TTTT
1100
TCCTGCTGCCATACTGT
2411
UCCUGCUGCCAUACUGUAU

exon_4

ATGCAGTACTGCA

GCAGUACUGCA

BCL11A_
−
CTTT
1101
TTCCTGCTGCCATACTG
2412
UUCCUGCUGCCAUACUGUA

exon_4

TATGCAGTACTGC

UGCAGUACUGC

BCL11A_
−
TTTT
1102
TGTAAATGGCAATGCAG
2413
UGUAAAUGGCAAUGCAGAA

exon_4

AATATTTTGTTAT

UAUUUUGUUAU

BCL11A_
−
GTTC
1103
CTTTTTCCTGCTGCCAT
2414
CUUUUUCCUGCUGCCAUAC

exon_4

ACTGTATGCAGTA

UGUAUGCAGUA

BCL11A_
−
TTTT
1104
GTTCCTTTTTCCTGCTG
2415
GUUCCUUUUUCCUGCUGCC

exon_4

CCATACTGTATGC

AUACUGUAUGC

BCL11A_
−
TTTT
1105
TGTTCCTTTTTCCTGCT
2416
UGUUCCUUUUUCCUGCUGC

exon_4

GCCATACTGTATG

CAUACUGUAUG

BCL11A_
−
TTTT
1106
TTGTTCCTTTTTCCTGC
2417
UUGUUCCUUUUUCCUGCUG

exon_4

TGCCATACTGTAT

CCAUACUGUAU

BCL11A_
−
CTTT
1107
TTTGTTCCTTTTTCCTG
2418
UUUGUUCCUUUUUCCUGCU

exon_4

CTGCCATACTGTA

GCCAUACUGUA

BCL11A_
−
GTTG
1108
TACATATCCTTTTTTGT
2419
UACAUAUCCUUUUUUGUUC

exon_4

TCCTTTTTCCTGC

CUUUUUCCUGC

BCL11A_
−
TTTG
1109
GGGGAGCCTGCTAGAAT
2420
GGGGAGCCUGCUAGAAUGU

exon_4

GTCACATGGATGG

CACAUGGAUGG

BCL11A_
−
TTTG
1110
TTCCTTTTTCCTGCTGC
2421
UUCCUUUUUCCUGCUGCCA

exon 4

CATACTGTATGCA

UACUGUAUGCA

BCL11A_
−
TTTT
1111
GTAAATGGCAATGCAGA
2422
GUAAAUGGCAAUGCAGAAU

exon 4

ATATTTTGTTATT

AUUUUGUUAUU

BCL11A_
−
TTTG
1112
TAAATGGCAATGCAGAA
2423
UAAAUGGCAAUGCAGAAUA

exon_4

TATTTTGTTATTG

UUUUGUUAUUG

BCL11A_
−
ATTT
1113
TGTTATTGGCCTTTTCT
2424
UGUUAUUGGCCUUUUCUAU

exon_4

ATTCCTGTAATGA

UCCUGUAAUGA

BCL11A_
−
GTTT
1114
TTATTTTTTTTTTTATT
2425
UUAUUUUUUUUUUUAUUUA

exon_4

TAGATGACCAAAG

GAUGACCAAAG

BCL11A_
−
TTTT
1115
TATTTTTTTTTTTATTT
2426
UAUUUUUUUUUUUAUUUAG

exon_4

AGATGACCAAAGG

AUGACCAAAGG

BCL11A_
−
TTTT
1116
ATTTTTTTTTTTATTTA
2427
AUUUUUUUUUUUAUUUAGA

exon_4

GATGACCAAAGGT

UGACCAAAGGU

BCL11A_
−
TTTA
1117
TTTTTTTTTTTATTTAG
2428
UUUUUUUUUUUAUUUAGAU

exon_4

ATGACCAAAGGTC

GACCAAAGGUC

BCL11A_
−
ATTT
1118
TTTTTTTTATTTAGATG
2429
UUUUUUUUAUUUAGAUGAC

exon_4

ACCAAAGGTCATT

CAAAGGUCAUU

BCL11A_
−
TTTT
1119
TTTTTTTATTTAGATGA
2430
UUUUUUUAUUUAGAUGACC

exon_4

CCAAAGGTCATTA

AAAGGUCAUUA

BCL11A_
−
TTTT
1120
TTTTTTATTTAGATGAC
2431
UUUUUUAUUUAGAUGACCA

exon_4

CAAAGGTCATTAC

AAGGUCAUUAC

BCL11A_
−
TTTT
1121
TTTTTATTTAGATGACC
2432
UUUUUAUUUAGAUGACCAA

exon_4

AAAGGTCATTACA

AGGUCAUUACA

BCL11A_
−
TTTT
1122
TTTTATTTAGATGACCA
2433
UUUUAUUUAGAUGACCAAA

exon 4

AAGGTCATTACAA

GGUCAUUACAA

BCL11A_
−
TTTT
1123
TTTATTTAGATGACCAA
2434
UUUAUUUAGAUGACCAAAG

exon_4

AGGTCATTACAAC

GUCAUUACAAC

BCL11A_
−
TTTT
1124
TTATTTAGATGACCAAA
2435
UUAUUUAGAUGACCAAAGG

exon_4

GGTCATTACAACC

UCAUUACAACC

BCL11A_
−
TTTT
1125
TATTTAGATGACCAAAG
2436
UAUUUAGAUGACCAAAGGU

exon_4

GTCATTACAACCT

CAUUACAACCU

BCL11A_
−
TTTT
1126
ATTTAGATGACCAAAGG
2437
AUUUAGAUGACCAAAGGUC

exon_4

TCATTACAACCTG

AUUACAACCUG

BCL11A_
−
TTTA
1127
TTTAGATGACCAAAGGT
2438
UUUAGAUGACCAAAGGUCA

exon_4

CATTACAACCTGG

UUACAACCUGG

BCL11A_
−
ATTT
1128
AGATGACCAAAGGTCAT
2439
AGAUGACCAAAGGUCAUUA

exon_4

TACAACCTGGCTT

CAACCUGGCUU

BCL11A_
−
TTTA
1129
GATGACCAAAGGTCATT
2440
GAUGACCAAAGGUCAUUAC

exon_4

ACAACCTGGCTTT

AACCUGGCUUU

BCL11A_
−
ATTA
1130
CAACCTGGCTTTTTATT
2441
CAACCUGGCUUUUUAUUGU

exon 4

GTATTTGTTTCTG

AUUUGUUUCUG

BCL11A_
−
ATTG
1131
GAAAAACCACTGTCTGT
2442
GAAAAACCACUGUCUGUGU

exon 4

GTTTTTTTGGCAG

UUUUUUGGCAG

BCL11A_
−
GTTC
1132
TATTGGAAAAACCACTG
2443
UAUUGGAAAAACCACUGUC

exon_4

TCTGTGTTTTTTT

UGUGUUUUUUU

BCL11A_
−
GTTA
1133
AGTTCTATTGGAAAAAC
2444
AGUUCUAUUGGAAAAACCA

exon_4

CACTGTCTGTGTT

CUGUCUGUGUU

BCL11A_
−
TTTG
1134
TTAAGTTCTATTGGAAA
2445
UUAAGUUCUAUUGGAAAAA

exon_4

AACCACTGTCTGT

CCACUGUCUGU

BCL11A_
−
CTTT
1135
GTTAAGTTCTATTGGAA
2446
GUUAAGUUCUAUUGGAAAA

exon_4

AAACCACTGTCTG

ACCACUGUCUG

BCL11A_
−
TTTC
1136
TGGTCTTTGTTAAGTTC
2447
UGGUCUUUGUUAAGUUCUA

exon_4

TATTGGAAAAACC

UUGGAAAAACC

BCL11A_
−
TTTG
1137
TTTTTATTTTTTTTTTT
2448
UUUUUAUUUUUUUUUUUAU

exon_4

ATTTAGATGACCA

UUAGAUGACCA

BCL11A_
−
GTTT
1138
CTGGTCTTTGTTAAGTT
2449
CUGGUCUUUGUUAAGUUCU

exon 4

CTATTGGAAAAAC

AUUGGAAAAAC

BCL11A_
−
ATTT
1139
GTTTCTGGTCTTTGTTA
2450
GUUUCUGGUCUUUGUUAAG

exon_4

AGTTCTATTGGAA

UUCUAUUGGAA

BCL11A_
−
ATTG
1140
TATTTGTTTCTGGTCTT
2451
UAUUUGUUUCUGGUCUUUG

exon 4

TGTTAAGTTCTAT

UUAAGUUCUAU

BCL11A_
−
TTTA
1141
TTGTATTTGTTTCTGGT
2452
UUGUAUUUGUUUCUGGUCU

exon 4

CTTTGTTAAGTTC

UUGUUAAGUUC

BCL11A_
−
TTTT
1142
ATTGTATTTGTTTCTGG
2453
AUUGUAUUUGUUUCUGGUC

exon 4

TCTTTGTTAAGTT

UUUGUUAAGUU

BCL11A_
−
TTTT
1143
TATTGTATTTGTTTCTG
2454
UAUUGUAUUUGUUUCUGGU

exon_4

GTCTTTGTTAAGT

CUUUGUUAAGU

BCL11A_
−
CTTT
1144
TTATTGTATTTGTTTCT
2455
UUAUUGUAUUUGUUUCUGG

exon_4

GGTCTTTGTTAAG

UCUUUGUUAAG

BCL11A_
−
TTTG
1145
TTTCTGGTCTTTGTTAA
2456
UUUCUGGUCUUUGUUAAGU

exon_4

GTTCTATTGGAAA

UCUAUUGGAAA

BCL11A_
−
TTTT
1146
TTGGTAGTGGAAAAAAA
2457
UUGGUAGUGGAAAAAAAAA

exon_4

AAAGACAGGCTGC

AGACAGGCUGC

BCL11A_
−
CTTT
1147
GTTTTTATTTTTTTTTT
2458
GUUUUUAUUUUUUUUUUUA

exon_4

TATTTAGATGACC

UUUAGAUGACC

BCL11A_
−
TTTT
1148
CTTTGTTTTTATTTTTT
2459
CUUUGUUUUUAUUUUUUUU

exon 4

TTTTTATTTAGAT

UUUAUUUAGAU

BCL11A_
−
TTTT
1149
GTTATTGGCCTTTTCTA
2460
GUUAUUGGCCUUUUCUAUU

exon 4

TTCCTGTAATGAA

CCUGUAAUGAA

BCL11A_
−
TTTG
1150
TTATTGGCCTTTTCTAT
2461
UUAUUGGCCUUUUCUAUUC

exon 4

TCCTGTAATGAAA

CUGUAAUGAAA

BCL11A_
−
GTTA
1151
TTGGCCTTTTCTATTCC
2462
UUGGCCUUUUCUAUUCCUG

exon_4

TGTAATGAAAGCT

UAAUGAAAGCU

BCL11A_
−
ATTG
1152
GCCTTTTCTATTCCTGT
2463
GCCUUUUCUAUUCCUGUAA

exon 4

AATGAAAGCTGTT

UGAAAGCUGUU

BCL11A_
−
CTTT
1153
TCTATTCCTGTAATGAA
2464
UCUAUUCCUGUAAUGAAAG

exon 4

AGCTGTTTGTCGT

CUGUUUGUCGU

BCL11A_
−
TTTT
1154
CTATTCCTGTAATGAAA
2465
CUAUUCCUGUAAUGAAAGC

exon_4

GCTGTTTGTCGTA

UGUUUGUCGUA

BCL11A_
−
TTTC
1155
TATTCCTGTAATGAAAG
2466
UAUUCCUGUAAUGAAAGCU

exon_4

CTGTTTGTCGTAA

GUUUGUCGUAA

BCL11A_
−
ATTC
1156
CTGTAATGAAAGCTGTT
2467
CUGUAAUGAAAGCUGUUUG

exon 4

TGTCGTAACTTGA

UCGUAACUUGA

BCL11A_
−
GTTT
1157
GTCGTAACTTGAAATTT
2468
GUCGUAACUUGAAAUUUUA

exon_4

TATCTTTTACTAT

UCUUUUACUAU

BCL11A_
−
TTTG
1158
TCGTAACTTGAAATTTT
2469
UCGUAACUUGAAAUUUUAU

exon_4

ATCTTTTACTATG

CUUUUACUAUG

BCL11A_
−
CTTG
1159
AAATTTTATCTTTTACT
2470
AAAUUUUAUCUUUUACUAU

exon_4

ATGGGAGTCACTA

GGGAGUCACUA

BCL11A_
−
ATTT
1160
TATCTTTTACTATGGGA
2471
UAUCUUUUACUAUGGGAGU

exon 4

GTCACTATTTATT

CACUAUUUAUU

BCL11A_
−
TTTT
1161
ATCTTTTACTATGGGAG
2472
AUCUUUUACUAUGGGAGUC

exon_4

TCACTATTTATTA

ACUAUUUAUUA

BCL11A_
−
TTTA
1162
TCTTTTACTATGGGAGT
2473
UCUUUUACUAUGGGAGUCA

exon_4

CACTATTTATTAT

CUAUUUAUUAU

BCL11A_
−
CTTT
1163
TACTATGGGAGTCACTA
2474
UACUAUGGGAGUCACUAUU

exon 4

TTTATTATTGCTT

UAUUAUUGCUU

BCL11A_
−
TTTT
1164
ACTATGGGAGTCACTAT
2475
ACUAUGGGAGUCACUAUUU

exon 4

TTATTATTGCTTA

AUUAUUGCUUA

BCL11A_
−
TTTA
1165
CTATGGGAGTCACTATT
2476
CUAUGGGAGUCACUAUUUA

exon_4

TATTATTGCTTAT

UUAUUGCUUAU

BCL11A_
−
TTTT
1166
TCTTTGTTTTTATTTTT
2477
UCUUUGUUUUUAUUUUUUU

exon 4

TTTTTTATTTAGA

UUUUAUUUAGA

BCL11A_
−
ATTT
1167
TTCTTTGTTTTTATTTT
2478
UUCUUUGUUUUUAUUUUUU

exon_4

TTTTTTTATTTAG

UUUUUAUUUAG

BCL11A_
−
TTTA
1168
TTTTTCTTTGTTTTTAT
2479
UUUUUCUUUGUUUUUAUUU

exon_4

TTTTTTTTTTATT

UUUUUUUUAUU

BCL11A_
−
TTTT
1169
ATTTTTCTTTGTTTTTA
2480
AUUUUUCUUUGUUUUUAUU

exon_4

TTTTTTTTTTTAT

UUUUUUUUUAU

BCL11A_
−
CTTT
1170
TATTTTTCTTTGTTTTT
2481
UAUUUUUCUUUGUUUUUAU

exon_4

ATTTTTTTTTTTA

UUUUUUUUUUA

BCL11A_
−
TTTG
1171
ATCTTTTATTTTTCTTT
2482
AUCUUUUAUUUUUCUUUGU

exon 4

GTTTTTATTTTTT

UUUUAUUUUUU

BCL11A_
−
TTTC
1172
TTTGTTTTTATTTTTTT
2483
UUUGUUUUUAUUUUUUUUU

exon_4

TTTTATTTAGATG

UUAUUUAGAUG

BCL11A_
−
ATTT
1173
GATCTTTTATTTTTCTT
2484
GAUCUUUUAUUUUUCUUUG

exon_4

TGTTTTTATTTTT

UUUUUAUUUUU

BCL11A_
−
GTTC
1174
AAAACAGAGGCACTTAA
2485
AAAACAGAGGCACUUAAUU

exon 4

TTTGATCTTTTAT

UGAUCUUUUAU

BCL11A_
−
CTTA
1175
TGTGCCCTGTTCAAAAC
2486
UGUGCCCUGUUCAAAACAG

exon_4

AGAGGCACTTAAT

AGGCACUUAAU

BCL11A_
−
ATTG
1176
CTTATGTGCCCTGTTCA
2487
CUUAUGUGCCCUGUUCAAA

exon_4

AAACAGAGGCACT

ACAGAGGCACU

BCL11A_
−
ATTA
1177
TTGCTTATGTGCCCTGT
2488
UUGCUUAUGUGCCCUGUUC

exon_4

TCAAAACAGAGGC

AAAACAGAGGC

BCL11A_
−
TTTA
1178
TTATTGCTTATGTGCCC
2489
UUAUUGCUUAUGUGCCCUG

exon 4

TGTTCAAAACAGA

UUCAAAACAGA

BCL11A_
−
ATTT
1179
ATTATTGCTTATGTGCC
2490
AUUAUUGCUUAUGUGCCCU

exon 4

CTGTTCAAAACAG

GUUCAAAACAG

BCL11A_
−
CTTA
1180
ATTTGATCTTTTATTTT
2491
AUUUGAUCUUUUAUUUUUC

exon 4

TCTTTGTTTTTAT

UUUGUUUUUAU

BCL11A_
−
CTTT
1181
TTTGGTAGTGGAAAAAA
2492
UUUGGUAGUGGAAAAAAAA

exon_4

AAAAGACAGGCTG

AAGACAGGCUG

BCL11A_
−
CTTA
1182
AAAGGTATCAATGTACC
2493
AAAGGUAUCAAUGUACCUU

exon_4

TTTTTTGGTAGTG

UUUUGGUAGUG

BCL11A_
−
GTTC
1183
TCTTAAAAGGTATCAAT
2494
UCUUAAAAGGUAUCAAUGU

exon_4

GTACCTTTTTTGG

ACCUUUUUUGG

BCL11A_
−
TTTC
1184
TCTAATCAGAGATACAG
2495
UCUAAUCAGAGAUACAGAG

exon_4

AGGTTGAGTATAA

GUUGAGUAUAA

BCL11A_
−
GTTG
1185
AGTATAAAATAAACCTG
2496
AGUAUAAAAUAAACCUGCU

exon_4

CTCAGATAGGACA

CAGAUAGGACA

BCL11A_
−
ATTA
1186
AGTGCACTGTACAATTT
2497
AGUGCACUGUACAAUUUUC

exon 4

TCCCAGTTTACAG

CCAGUUUACAG

BCL11A_
−
ATTT
1187
TCCCAGTTTACAGGTCT
2498
UCCCAGUUUACAGGUCUAU

exon 4

ATACTTAAGGGAA

ACUUAAGGGAA

BCL11A_
−
TTTT
1188
CCCAGTTTACAGGTCTA
2499
CCCAGUUUACAGGUCUAUA

exon_4

TACTTAAGGGAAA

CUUAAGGGAAA

BCL11A_
−
TTTC
1189
CCAGTTTACAGGTCTAT
2500
CCAGUUUACAGGUCUAUAC

exon 4

ACTTAAGGGAAAA

UUAAGGGAAAA

BCL11A_
−
GTTT
1190
ACAGGTCTATACTTAAG
2501
ACAGGUCUAUACUUAAGGG

exon_4

GGAAAAGTTGCAA

AAAAGUUGCAA

BCL11A_
−
TTTA
1191
CAGGTCTATACTTAAGG
2502
CAGGUCUAUACUUAAGGGA

exon_4

GAAAAGTTGCAAG

AAAGUUGCAAG

BCL11A_
−
CTTA
1192
AGGGAAAAGTTGCAAGA
2503
AGGGAAAAGUUGCAAGAAU

exon_4

ATGCTGAAAAAAA

GCUGAAAAAAA

BCL11A_
−
GTTG
1193
CAAGAATGCTGAAAAAA
2504
CAAGAAUGCUGAAAAAAAA

exon 4

AATTGAACACAAT

UUGAACACAAU

BCL11A_
−
ATTG
1194
AACACAATCTCATTGAG
2505
AACACAAUCUCAUUGAGGA

exon 4

GAGCATTTTTTAA

GCAUUUUUUAA

BCL11A_
−
ATTG
1195
AGGAGCATTTTTTAAAA
2506
AGGAGCAUUUUUUAAAAAC

exon_4

ACTAAAAAAAAAA

UAAAAAAAAAA

BCL11A_
−
ATTT
1196
TTTAAAAACTAAAAAAA
2507
UUUAAAAACUAAAAAAAAA

exon 4

AAAAAACTTTGCC

AAAACUUUGCC

BCL11A_
−
TTTT
1197
TTAAAAACTAAAAAAAA
2508
UUAAAAACUAAAAAAAAAA

exon_4

AAAAACTTTGCCA

AAACUUUGCCA

BCL11A_
−
TTTT
1198
TAAAAACTAAAAAAAAA
2509
UAAAAACUAAAAAAAAAAA

exon_4

AAAACTTTGCCAG

AACUUUGCCAG

BCL11A_
−
TTTT
1199
AAAAACTAAAAAAAAAA
2510
AAAAACUAAAAAAAAAAAA

exon_4

AAACTTTGCCAGC

ACUUUGCCAGC

BCL11A_
−
TTTA
1200
AAAACTAAAAAAAAAAA
2511
AAAACUAAAAAAAAAAAAA

exon_4

AACTTTGCCAGCC

CUUUGCCAGCC

BCL11A_
−
TTTC
1201
GCTTCTACAGTGCAAGG
2512
GCUUCUACAGUGCAAGGAU

exon_4

ATTTTTTTGTACA

UUUUUUGUACA

BCL11A_
−
CTTT
1202
CGCTTCTACAGTGCAAG
2513
CGCUUCUACAGUGCAAGGA

exon_4

GATTTTTTTGTAC

UUUUUUUGUAC

BCL11A_
−
ATTG
1203
CTTTCGCTTCTACAGTG
2514
CUUUCGCUUCUACAGUGCA

exon_4

CAAGGATTTTTTT

AGGAUUUUUUU

BCL11A_
−
CTTA
1204
ACATAGAAATGAATGAT
2515
ACAUAGAAAUGAAUGAUUG

exon_4

TGCTTTCGCTTCT

CUUUCGCUUCU

BCL11A_
−
ATTG
1205
CAAGCGCTGTGAATGGA
2516
CAAGCGCUGUGAAUGGAAA

exon_4

AACAGAATACACT

CAGAAUACACU

BCL11A_
−
CTTG
1206
GACGCAACATTGCAAGC
2517
GACGCAACAUUGCAAGCGC

exon_4

GCTGTGAATGGAA

UGUGAAUGGAA

BCL11A_
−
TTTT
1207
CTCTAATCAGAGATACA
2518
CUCUAAUCAGAGAUACAGA

exon 4

GAGGTTGAGTATA

GGUUGAGUAUA

BCL11A_
−
CTTA
1208
CTTGGACGCAACATTGC
2519
CUUGGACGCAACAUUGCAA

exon 4

AAGCGCTGTGAAT

GCGCUGUGAAU

BCL11A_
−
ATTG
1209
AGCTTACTTACTTGGAC
2520
AGCUUACUUACUUGGACGC

exon 4

GCAACATTGCAAG

AACAUUGCAAG

BCL11A_
−
CTTG
1210
ACTATTGAGCTTACTTA
2521
ACUAUUGAGCUUACUUACU

exon_4

CTTGGACGCAACA

UGGACGCAACA

BCL11A_
−
TTTA
1211
CTTGACTATTGAGCTTA
2522
CUUGACUAUUGAGCUUACU

exon_4

CTTACTTGGACGC

UACUUGGACGC

BCL11A_
−
ATTT
1212
ACTTGACTATTGAGCTT
2523
ACUUGACUAUUGAGCUUAC

exon_4

ACTTACTTGGACG

UUACUUGGACG

BCL11A_
−
TTTG
1213
CCAGCCATTTACTTGAC
2524
CCAGCCAUUUACUUGACUA

exon_4

TATTGAGCTTACT

UUGAGCUUACU

BCL11A_
−
CTTT
1214
GCCAGCCATTTACTTGA
2525
GCCAGCCAUUUACUUGACU

exon_4

CTATTGAGCTTAC

AUUGAGCUUAC

BCL11A_
−
CTTA
1215
CTTACTTGGACGCAACA
2526
CUUACUUGGACGCAACAUU

exon_4

TTGCAAGCGCTGT

GCAAGCGCUGU

BCL11A_
−
CTTC
1216
TACAGTGCAAGGATTTT
2527
UACAGUGCAAGGAUUUUUU

exon_4

TTTGTACAAAACT

UGUACAAAACU

BCL11A_
−
CTTT
1217
TCTCTAATCAGAGATAC
2528
UCUCUAAUCAGAGAUACAG

exon_4

AGAGGTTGAGTAT

AGGUUGAGUAU

BCL11A_
−
GTTC
1218
AAATAGCACTTGACTCT
2529
AAAUAGCACUUGACUCUGC

exon 4

GCCTGTGATATCT

CUGUGAUAUCU

BCL11A_
−
ATTT
1219
GTGTTAACATGGAAGAG
2530
GUGUUAACAUGGAAGAGGA

exon_4

GATTCATTGTTTT

UUCAUUGUUUU

BCL11A_
−
TTTG
1220
TGTTAACATGGAAGAGG
2531
UGUUAACAUGGAAGAGGAU

exon_4

ATTCATTGTTTTT

UCAUUGUUUUU

BCL11A_
−
GTTA
1221
ACATGGAAGAGGATTCA
2532
ACAUGGAAGAGGAUUCAUU

exon_4

TTGTTTTTATTTT

GUUUUUAUUUU

BCL11A_
−
ATTC
1222
ATTGTTTTTATTTTTAT
2533
AUUGUUUUUAUUUUUAUUU

exon_4

TTTTTTAATTTTT

UUUUAAUUUUU

BCL11A_
−
ATTG
1223
TTTTTATTTTTATTTTT
2534
UUUUUAUUUUUAUUUUUUU

exon_4

TTAATTTTTTCTT

AAUUUUUUCUU

BCL11A_
−
GTTT
1224
TTATTTTTATTTTTTTA
2535
UUAUUUUUAUUUUUUUAAU

exon_4

ATTTTTTCTTTTT

UUUUUUUUUU

BCL11A_
−
TTTT
1225
TATTTTTATTTTTTTAA
2536
UAUUUUUAUUUUUUUAAUU

exon 4

TTTTTTCTTTTTT

UUUUCUUUUUU

BCL11A_
−
TTTT
1226
ATTTTTATTTTTTTAAT
2537
AUUUUUAUUUUUUUAAUUU

exon 4

TTTTTCTTTTTTA

UUUCUUUUUUA

BCL11A_
−
TTTA
1227
TTTTTATTTTTTTAATT
2538
UUUUUAUUUUUUUAAUUUU

exon_4

TTTTCTTTTTTAT

UUCUUUUUUAU

BCL11A_
−
ATTT
1228
TTATTTTTTTAATTTTT
2539
UUAUUUUUUUAAUUUUUUC

exon 4

TCTTTTTTATTAA

UUUUUUAUUAA

BCL11A_
−
TTTT
1229
TATTTTTTTAATTTTTT
2540
UAUUUUUUUAAUUUUUUCU

exon 4

CTTTTTTATTAAG

UUUUUAUUAAG

BCL11A_
−
TTTT
1230
ATTTTTTTAATTTTTTC
2541
AUUUUUUUAAUUUUUUCUU

exon 4

TTTTTTATTAAGC

UUUUAUUAAGC

BCL11A_
−
TTTA
1231
TTTTTTTAATTTTTTCT
2542
UUUUUUUAAUUUUUUCUUU

exon_4

TTTTTATTAAGCT

UUUAUUAAGCU

BCL11A_
−
ATTT
1232
TTTTAATTTTTTCTTTT
2543
UUUUAAUUUUUUCUUUUUU

exon 4

TTATTAAGCTAGC

AUUAAGCUAGC

BCL11A_
−
TTTT
1233
TTTAATTTTTTCTTTTT
2544
UUUAAUUUUUUCUUUUUUA

exon 4

TATTAAGCTAGCA

UUAAGCUAGCA

BCL11A_
−
TTTT
1234
TTAATTTTTTCTTTTTT
2545
UUAAUUUUUUCUUUUUUAU

exon_4

ATTAAGCTAGCAT

UAAGCUAGCAU

BCL11A_
−
TTTT
1235
TAATTTTTTCTTTTTTA
2546
UAAUUUUUUCUUUUUUAUU

exon_4

TTAAGCTAGCATC

AAGCUAGCAUC

BCL11A_
−
GTTG
1236
GTGTTCAAATAGCACTT
2547
GUGUUCAAAUAGCACUUGA

exon 4

GACTCTGCCTGTG

CUCUGCCUGUG

BCL11A_
−
ATTA
1237
AGCTAGCATCTGCCCCA
2548
AGCUAGCAUCUGCCCCAGU

exon 4

GTTGGTGTTCAAA

UGGUGUUCAAA

BCL11A_
−
TTTA
1238
TTAAGCTAGCATCTGCC
2549
UUAAGCUAGCAUCUGCCCC

exon 4

CCAGTTGGTGTTC

AGUUGGUGUUC

BCL11A_
−
TTTT
1239
ATTAAGCTAGCATCTGC
2550
AUUAAGCUAGCAUCUGCCC

exon 4

CCCAGTTGGTGTT

CAGUUGGUGUU

BCL11A_
−
TTTT
1240
TATTAAGCTAGCATCTG
2551
UAUUAAGCUAGCAUCUGCC

exon_4

CCCCAGTTGGTGT

CCAGUUGGUGU

BCL11A_
−
TTTT
1241
TTATTAAGCTAGCATCT
2552
UUAUUAAGCUAGCAUCUGC

exon_4

GCCCCAGTTGGTG

CCCAGUUGGUG

BCL11A_
−
CTTG
1242
ACTCTGCCTGTGATATC
2553
ACUCUGCCUGUGAUAUCUG

exon_4

TGTATCTTTTCTC

UAUCUUUUCUC

BCL11A_
−
CTTT
1243
TTTATTAAGCTAGCATC
2554
UUUAUUAAGCUAGCAUCUG

exon_4

TGCCCCAGTTGGT

CCCCAGUUGGU

BCL11A_
−
TTTT
1244
CTTTTTTATTAAGCTAG
2555
CUUUUUUAUUAAGCUAGCA

exon_4

CATCTGCCCCAGT

UCUGCCCCAGU

BCL11A_
−
TTTT
1245
TCTTTTTTATTAAGCTA
2556
UCUUUUUUAUUAAGCUAGC

exon_4

GCATCTGCCCCAG

AUCUGCCCCAG

BCL11A_
−
TTTT
1246
TTCTTTTTTATTAAGCT
2557
UUCUUUUUUAUUAAGCUAG

exon_4

AGCATCTGCCCCA

CAUCUGCCCCA

BCL11A_
−
ATTT
1247
TTTCTTTTTTATTAAGC
2558
UUUUUUUUUAUUAAGCUA

exon 4

TAGCATCTGCCCC

GCAUCUGCCCC

BCL11A_
−
TTTA
1248
ATTTTTTCTTTTTTATT
2559
AUUUUUUCUUUUUUAUUAA

exon_4

AAGCTAGCATCTG

GCUAGCAUCUG

BCL11A_
−
TTTT
1249
AATTTTTTCTTTTTTAT
2560
AAUUUUUUCUUUUUUAUUA

exon 4

TAAGCTAGCATCT

AGCUAGCAUCU

BCL11A_
−
TTTC
1250
TTTTTTATTAAGCTAGC
2561
UUUUUUAUUAAGCUAGCAU

exon 4

ATCTGCCCCAGTT

CUGCCCCAGUU

BCL11A_
−
TTTT
1251
CCATACACTGTGTGCTA
2562
CCAUACACUGUGUGCUAUU

exon 4

TTTGTGTTAACAT

UGUGUUAACAU

BCL11A_
−
ATTT
1252
TTTTGTACAAAACTTTT
2563
UUUUGUACAAAACUUUUUU

exon_4

TTAAATATAAATG

AAAUAUAAAUG

BCL11A_
−
TTTT
1253
TTGTACAAAACTTTTTT
2564
UUGUACAAAACUUUUUUAA

exon 4

AAATATAAATGTT

AUAUAAAUGUU

BCL11A_
−
ATTG
1254
GGGAAAGGTTTAAGATT
2565
GGGAAAGGUUUAAGAUUAU

exon 4

ATATAGTACTTAA

AUAGUACUUAA

BCL11A_
−
GTTT
1255
AAGATTATATAGTACTT
2566
AAGAUUAUAUAGUACUUAA

exon 4

AAATATAGGAAAA

AUAUAGGAAAA

BCL11A_
−
TTTA
1256
AGATTATATAGTACTTA
2567
AGAUUAUAUAGUACUUAAA

exon 4

AATATAGGAAAAT

UAUAGGAAAAU

BCL11A_
−
ATTA
1257
TATAGTACTTAAATATA
2568
UAUAGUACUUAAAUAUAGG

exon 4

GGAAAATGCACAC

AAAAUGCACAC

BCL11A_
−
CTTA
1258
AATATAGGAAAATGCAC
2569
AAUAUAGGAAAAUGCACAC

exon 4

ACTCATGTTGATT

UCAUGUUGAUU

BCL11A_
−
GTTG
1259
ATTCCTATGCTAAAATA
2570
AUUCCUAUGCUAAAAUACA

exon_4

CATTTATGGTCTT

UUUAUGGUCUU

BCL11A_
−
ATTC
1260
CTATGCTAAAATACATT
2571
CUAUGCUAAAAUACAUUUA

exon_4

TATGGTCTTTTTT

UGGUCUUUUUU

BCL11A_
−
ATTT
1261
ATGGTCTTTTTTCTGTA
2572
AUGGUCUUUUUUCUGUAUU

exon_4

TTTCTAGAATGGT

UCUAGAAUGGU

BCL11A_
−
TTTA
1262
TGGTCTTTTTTCTGTAT
2573
UGGUCUUUUUUCUGUAUUU

exon_4

TTCTAGAATGGTA

CUAGAAUGGUA

BCL11A_
−
CTTT
1263
TTTCTGTATTTCTAGAA
2574
UUUCUGUAUUUCUAGAAUG

exon_4

TGGTATTTGAATT

GUAUUUGAAUU

BCL11A_
−
TTTT
1264
TTCTGTATTTCTAGAAT
2575
UUCUGUAUUUCUAGAAUGG

exon_4

GGTATTTGAATTA

UAUUUGAAUUA

BCL11A_
−
TTTT
1265
TCTGTATTTCTAGAATG
2576
UCUGUAUUUCUAGAAUGGU

exon_4

GTATTTGAATTAA

AUUUGAAUUAA

BCL11A_
−
TTTT
1266
CTGTATTTCTAGAATGG
2577
CUGUAUUUCUAGAAUGGUA

exon_4

TATTTGAATTAAA

UUUGAAUUAAA

BCL11A_
−
TTTC
1267
TGTATTTCTAGAATGGT
2578
UGUAUUUCUAGAAUGGUAU

exon_4

ATTTGAATTAAAT

UUGAAUUAAAU

BCL11A_
−
ATTT
1268
CTAGAATGGTATTTGAA
2579
CUAGAAUGGUAUUUGAAUU

exon_4

TTAAATGTTCATC

AAAUGUUCAUC

BCL11A_
−
TTTC
1269
TAGAATGGTATTTGAAT
2580
UAGAAUGGUAUUUGAAUUA

exon_4

TAAATGTTCATCT

AAUGUUCAUCU

BCL11A_
−
ATTT
1270
GAATTAAATGTTCATCT
2581
GAAUUAAAUGUUCAUCUAG

exon_4

AGTGTTAGGCACT

UGUUAGGCACU

BCL11A_
−
CTTG
1271
TTCTCTTAAAAGGTATC
2582
UUCUCUUAAAAGGUAUCAA

exon_4

AATGTACCTTTTT

UGUACCUUUUU

BCL11A_
−
GTTG
1272
CTTGTTCTCTTAAAAGG
2583
CUUGUUCUCUUAAAAGGUA

exon_4

TATCAATGTACCT

UCAAUGUACCU

BCL11A_
−
TTTA
1273
ACTGTTGCTTGTTCTCT
2584
ACUGUUGCUUGUUCUCUUA

exon_4

TAAAAGGTATCAA

AAAGGUAUCAA

BCL11A_
−
TTTT
1274
AACTGTTGCTTGTTCTC
2585
AACUGUUGCUUGUUCUCUU

exon 4

TTAAAAGGTATCA

AAAAGGUAUCA

BCL11A_
−
TTTT
1275
TAACTGTTGCTTGTTCT
2586
UAACUGUUGCUUGUUCUCU

exon 4

CTTAAAAGGTATC

UAAAAGGUAUC

BCL11A_
−
ATTT
1276
TTAACTGTTGCTTGTTC
2587
UUAACUGUUGCUUGUUCUC

exon 4

TCTTAAAAGGTAT

UUAAAAGGUAU

BCL11A_
−
GTTG
1277
TAAAAAAAAAAAACATA
2588
UAAAAAAAAAAAACAUACA

exon_4

CATTGGGGAAAGG

UUGGGGAAAGG

BCL11A_
−
CTTG
1278
TATTTTTAACTGTTGCT
2589
UAUUUUUAACUGUUGCUUG

exon 4

TGTTCTCTTAAAA

UUCUCUUAAAA

BCL11A_
−
TTTA
1279
TATTGAAGCTTGTATTT
2590
UAUUGAAGCUUGUAUUUUU

exon_4

TTAACTGTTGCTT

AACUGUUGCUU

BCL11A_
−
ATTT
1280
ATATTGAAGCTTGTATT
2591
AUAUUGAAGCUUGUAUUUU

exon_4

TTTAACTGTTGCT

UAACUGUUGCU

BCL11A_
−
GTTA
1281
GGCACTATAGTATTTAT
2592
GGCACUAUAGUAUUUAUAU

exon_4

ATTGAAGCTTGTA

UGAAGCUUGUA

BCL11A_
−
GTTC
1282
ATCTAGTGTTAGGCACT
2593
AUCUAGUGUUAGGCACUAU

exon_4

ATAGTATTTATAT

AGUAUUUAUAU

BCL11A_
−
ATTA
1283
AATGTTCATCTAGTGTT
2594
AAUGUUCAUCUAGUGUUAG

exon_4

AGGCACTATAGTA

GCACUAUAGUA

BCL11A_
−
TTTG
1284
AATTAAATGTTCATCTA
2595
AAUUAAAUGUUCAUCUAGU

exon_4

GTGTTAGGCACTA

GUUAGGCACUA

BCL11A_
−
ATTG
1285
AAGCTTGTATTTTTAAC
2596
AAGCUUGUAUUUUUAACUG

exon 4

TGTTGCTTGTTCT

UUGCUUGUUCU

BCL11A_
−
TTTT
1286
TTTGTACAAAACTTTTT
2597
UUUGUACAAAACUUUUUUA

exon 4

TAAATATAAATGT

AAUAUAAAUGU

BCL11A_
−
CTTC
1287
AGGTTGTAAAAAAAAAA
2598
AGGUUGUAAAAAAAAAAAA

exon 4

AACATACATTGGG

CAUACAUUGGG

BCL11A_
−
ATTC
1288
TATGCCTTGGATACACA
2599
UAUGCCUUGGAUACACACC

exon 4

CCGCTCTTCAGGT

GCUCUUCAGGU

BCL11A_
−
TTTT
1289
TGTACAAAACTTTTTTA
2600
UGUACAAAACUUUUUUAAA

exon_4

AATATAAATGTTA

UAUAAAUGUUA

BCL11A_
−
TTTT
1290
GTACAAAACTTTTTTAA
2601
GUACAAAACUUUUUUAAAU

exon_4

ATATAAATGTTAA

AUAAAUGUUAA

BCL11A_
−
TTTG
1291
TACAAAACTTTTTTAAA
2602
UACAAAACUUUUUUAAAUA

exon_4

TATAAATGTTAAG

UAAAUGUUAAG

BCL11A_
−
CTTT
1292
TTTAAATATAAATGTTA
2603
UUUAAAUAUAAAUGUUAAG

exon_4

AGAAAAATTTTTT

AAAAAUUUUUU

BCL11A_
−
TTTT
1293
TTAAATATAAATGTTAA
2604
UUAAAUAUAAAUGUUAAGA

exon_4

GAAAAATTTTTTT

AAAAUUUUUUU

BCL11A_
−
TTTT
1294
TAAATATAAATGTTAAG
2605
UAAAUAUAAAUGUUAAGAA

exon_4

AAAAATTTTTTTT

AAAUUUUUUUU

BCL11A_
−
TTTT
1295
AAATATAAATGTTAAGA
2606
AAAUAUAAAUGUUAAGAAA

exon 4

AAAATTTTTTTTA

AAUUUUUUUUA

BCL11A_
−
TTTA
1296
AATATAAATGTTAAGAA
2607
AAUAUAAAUGUUAAGAAAA

exon_4

AAATTTTTTTTAA

AUUUUUUUUAA

BCL11A_
−
GTTA
1297
AGAAAAATTTTTTTTAA
2608
AGAAAAAUUUUUUUUAAAA

exon_4

AAAACACTTCATT

AACACUUCAUU

BCL11A_
−
ATTT
1298
TTTTTAAAAAACACTTC
2609
UUUUUAAAAAACACUUCAU

exon_4

ATTATGTTTAGGG

UAUGUUUAGGG

BCL11A_
−
TTTT
1299
TTTTAAAAAACACTTCA
2610
UUUUAAAAAACACUUCAUU

exon_4

TTATGTTTAGGGG

AUGUUUAGGGG

BCL11A_
−
TTTT
1300
TTTAAAAAACACTTCAT
2611
UUUAAAAAACACUUCAUUA

exon 4

TATGTTTAGGGGG

UGUUUAGGGGG

BCL11A_
−
TTTT
1301
TTAAAAAACACTTCATT
2612
UUAAAAAACACUUCAUUAU

exon_4

ATGTTTAGGGGGG

GUUUAGGGGGG

BCL11A_
−
TTTT
1302
TAAAAAACACTTCATTA
2613
UAAAAAACACUUCAUUAUG

exon 4

TGTTTAGGGGGGA

UUUAGGGGGGA

BCL11A_
−
TTTT
1303
AAAAAACACTTCATTAT
2614
AAAAAACACUUCAUUAUGU

exon_4

GTTTAGGGGGGAA

UUAGGGGGGAA

BCL11A_
−
TTTA
1304
AAAAACACTTCATTATG
2615
AAAAACACUUCAUUAUGUU

exon 4

TTTAGGGGGGAAC

UAGGGGGGAAC

BCL11A_
−
CTTC
1305
ATTATGTTTAGGGGGGA
2616
AUUAUGUUUAGGGGGGAAC

exon 4

ACTGCATTTTAGG

UGCAUUUUAGG

BCL11A_
−
TTTA
1306
AAAATGGTAGTGGAAAT
2617
AAAAUGGUAGUGGAAAUUC

exon_4

TCTATGCCTTGGA

UAUGCCUUGGA

BCL11A_
−
ATTT
1307
AAAAATGGTAGTGGAAA
2618
AAAAAUGGUAGUGGAAAUU

exon_4

TTCTATGCCTTGG

CUAUGCCUUGG

BCL11A_
−
GTTA
1308
TCCATTTAAAAATGGTA
2619
UCCAUUUAAAAAUGGUAGU

exon_4

GTGGAAATTCTAT

GGAAAUUCUAU

BCL11A_
−
CTTG
1309
TTATCCATTTAAAAATG
2620
UUAUCCAUUUAAAAAUGGU

exon_4

GTAGTGGAAATTC

AGUGGAAAUUC

BCL11A_
−
GTTA
1310
CAAGACTTGTTATCCAT
2621
CAAGACUUGUUAUCCAUUU

exon_4

TTAAAAATGGTAG

AAAAAUGGUAG

BCL11A_
−
CTTG
1311
GTGGTGTTACAAGACTT
2622
GUGGUGUUACAAGACUUGU

exon_4

GTTATCCATTTAA

UAUCCAUUUAA

BCL11A_
−
CTTG
1312
GATACACACCGCTCTTC
2623
GAUACACACCGCUCUUCAG

exon_4

AGGTTGTAAAAAA

GUUGUAAAAAA

BCL11A_
−
ATTG
1313
TCTTGGTGGTGTTACAA
2624
UCUUGGUGGUGUUACAAGA

exon_4

GACTTGTTATCCA

CUUGUUAUCCA

BCL11A_
−
TTTA
1314
GGGTTCCATTGTCTTGG
2625
GGGUUCCAUUGUCUUGGUG

exon_4

TGGTGTTACAAGA

GUGUUACAAGA

BCL11A_
−
TTTT
1315
AGGGTTCCATTGTCTTG
2626
AGGGUUCCAUUGUCUUGGU

exon_4

GTGGTGTTACAAG

GGUGUUACAAG

BCL11A_
−
ATTT
1316
TAGGGTTCCATTGTCTT
2627
UAGGGUUCCAUUGUCUUGG

exon_4

GGTGGTGTTACAA

UGGUGUUACAA

BCL11A_
−
TTTA
1317
GGGGGGAACTGCATTTT
2628
GGGGGGAACUGCAUUUUAG

exon_4

AGGGTTCCATTGT

GGUUCCAUUGU

BCL11A_
−
GTTT
1318
AGGGGGGAACTGCATTT
2629
AGGGGGGAACUGCAUUUUA

exon_4

TAGGGTTCCATTG

GGGUUCCAUUG

BCL11A_
−
ATTA
1319
TGTTTAGGGGGGAACTG
2630
UGUUUAGGGGGGAACUGCA

exon_4

CATTTTAGGGTTC

UUUUAGGGUUC

BCL11A_
−
GTTC
1320
CATTGTCTTGGTGGTGT
2631
CAUUGUCUUGGUGGUGUUA

exon_4

TACAAGACTTGTT

CAAGACUUGUU

BCL11A_
+
TTTA
1321
CCTGCAAAATAATACAA
2632
CCUGCAAAAUAAUACAACA

exon_4

CACCAACATCAAT

CCAACAUCAAU

The invention includes all combinations of the direct repeats and spacers listed above, consistent with the disclosure herein.

In some embodiments, one or more RNA guides disrupt the GATAA motif of the enhancer region of the BCL11A gene. In some embodiments, two RNA guides disrupt the GATAA motif of the enhancer region of the BCL11A gene. For example, in some embodiments, the RNA guide of SEQ ID NO: 2677 (or an RNA guide with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 2677) and the RNA guide of SEQ ID NO: 2678 (or an RNA guide with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 2678) disrupt the GATAA motif. In other embodiments, the RNA guide of SEQ ID NO: 2677 (or an RNA guide with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 2677) and the RNA guide of SEQ ID NO: 2679 (or an RNA guide with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 2679) disrupt the GATAA motif. In yet other embodiments, the RNA guide of SEQ ID NO: 2678 (or an RNA guide with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 2678) and the RNA guide of SEQ ID NO: 2679 (or an RNA guide with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 2679) disrupt the GATAA motif.

In embodiments, the RNA guide does not consist of the sequence of

(SEQ ID NO: 2677)

AGAAAUCCGUCUUUCAUUGACGGGAAGCUAGUCUAGUGCAAGC;

(SEQ ID NO: 2678)

AGAAAUCCGUCUUUCAUUGACGGCUGGAGCCUGUGAUAAAAGC;

or

(SEQ ID NO: 2679)

AGAAAUCCGUCUUUCAUUGACGGUACCCCACCCACGCCCCCAC.

In some embodiments, a spacer sequence described herein comprises a uracil (U). In some embodiments, a spacer sequence described herein comprises a thymine (T). In some embodiments, a spacer sequence according to Table 5 comprises a sequence comprising a thymine in one or more places indicated as uracil in Table 5.

Modifications

The RNA guide may include one or more covalent modifications with respect to a reference sequence, in particular the parent polyribonucleotide, which are included within the scope of this invention.

Exemplary modifications can include any modification to the sugar, the nucleobase, the internucleoside linkage (e.g. to a linking phosphate/to a phosphodiester linkage/to the phosphodiester backbone), and any combination thereof. Some of the exemplary modifications provided herein are described in detail below.

The RNA guide may include any useful modification, such as to the sugar, the nucleobase, or the internucleoside linkage (e.g. to a linking phosphate/to a phosphodiester linkage/to the phosphodiester backbone). One or more atoms of a pyrimidine nucleobase may be replaced or substituted with optionally substituted amino, optionally substituted thiol, optionally substituted alkyl (e.g., methyl or ethyl), or halo (e.g., chloro or fluoro). In certain embodiments, modifications (e.g., one or more modifications) are present in each of the sugar and the internucleoside linkage. Modifications may be modifications of ribonucleic acids (RNAs) to deoxyribonucleic acids (DNAs), threose nucleic acids (TNAs), glycol nucleic acids (GNAs), peptide nucleic acids (PNAs), locked nucleic acids (LNAs) or hybrids thereof). Additional modifications are described herein.

In some embodiments, the modification may include a chemical or cellular induced modification. For example, some nonlimiting examples of intracellular RNA modifications are described by Lewis and Pan in “RNA modifications and structures cooperate to guide RNA-protein interactions” from Nat Reviews Mol Cell Biol, 2017, 18:202-210.

Different sugar modifications, nucleotide modifications, and/or internucleoside linkages (e.g., backbone structures) may exist at various positions in the sequence. One of ordinary skill in the art will appreciate that the nucleotide analogs or other modification(s) may be located at any position(s) of the sequence, such that the function of the sequence is not substantially decreased. The sequence may include from about 1% to about 100% modified nucleotides (either in relation to overall nucleotide content, or in relation to one or more types of nucleotide, i.e. any one or more of A, G, U or C) or any intervening percentage (e.g., from 1% to 20%>, from 1% to 25%, from 1% to 50%, from 1% to 60%, from 1% to 70%, from 1% to 80%, from 1% to 90%, from 1% to 95%, from 10% to 20%, from 10% to 25%, from 10% to 50%, from 10% to 60%, from 10% to 70%, from 10% to 80%, from 10% to 90%, from 10% to 95%, from 10% to 100%, from 20% to 25%, from 20% to 50%, from 20% to 60%, from 20% to 70%, from 20% to 80%, from 20% to 90%, from 20% to 95%, from 20% to 100%, from 50% to 60%, from 50% to 70%, from 50% to 80%, from 50% to 90%, from 50% to 95%, from 50% to 100%, from 70% to 80%, from 70% to 90%, from 70% to 95%, from 70% to 100%, from 80% to 90%, from 80% to 95%, from 80% to 100%, from 90% to 95%, from 90% to 100%, and from 95% to 100%).

In some embodiments, sugar modifications (e.g., at the 2′ position or 4′ position) or replacement of the sugar at one or more ribonucleotides of the sequence may, as well as backbone modifications, include modification or replacement of the phosphodiester linkages. Specific examples of a sequence include, but are not limited to, sequences including modified backbones or no natural internucleoside linkages such as internucleoside modifications, including modification or replacement of the phosphodiester linkages. Sequences having modified backbones include, among others, those that do not have a phosphorus atom in the backbone. For the purposes of this application, and as sometimes referenced in the art, modified RNAs that do not have a phosphorus atom in their internucleoside backbone can also be considered to be oligonucleosides. In particular embodiments, a sequence will include ribonucleotides with a phosphorus atom in its internucleoside backbone.

Modified sequence backbones may include, for example, phosphorothioates, chiral phosphorothioates, phosphorodithioates, phosphotriesters, aminoalkylphosphotriesters, methyl and other alkyl phosphonates such as 3′-alkylene phosphonates and chiral phosphonates, phosphinates, phosphoramidates such as 3′-amino phosphoramidate and aminoalkylphosphoramidates, thionophosphoramidates, thionoalkylphosphonates, thionoalkylphosphotriesters, and boranophosphates having normal 3′-5′ linkages, 2′-5′ linked analogs of these, and those having inverted polarity wherein the adjacent pairs of nucleoside units are linked 3′-5′ to 5′-3′ or 2′-5′ to 5′-2′. Various salts, mixed salts and free acid forms are also included. In some embodiments, the sequence may be negatively or positively charged.

The modified nucleotides, which may be incorporated into the sequence, can be modified on the internucleoside linkage (e.g., phosphate backbone). Herein, in the context of the polynucleotide backbone, the phrases “phosphate” and “phosphodiester” are used interchangeably. Backbone phosphate groups can be modified by replacing one or more of the oxygen atoms with a different substituent. Further, the modified nucleosides and nucleotides can include the wholesale replacement of an unmodified phosphate moiety with another internucleoside linkage as described herein. Examples of modified phosphate groups include, but are not limited to, phosphorothioate, phosphoroselenates, boranophosphates, boranophosphate esters, hydrogen phosphonates, phosphoramidates, phosphorodiamidates, alkyl or aryl phosphonates, and phosphotriesters. Phosphorodithioates have both non-linking oxygens replaced by sulfur. The phosphate linker can also be modified by the replacement of a linking oxygen with nitrogen (bridged phosphoramidates), sulfur (bridged phosphorothioates), and carbon (bridged methylene-phosphonates).

The α-thio substituted phosphate moiety is provided to confer stability to RNA and DNA polymers through the unnatural phosphorothioate backbone linkages. Phosphorothioate DNA and RNA have increased nuclease resistance and subsequently a longer half-life in a cellular environment.

In specific embodiments, a modified nucleoside includes an alpha-thio-nucleoside (e.g., 5′-O-(1-thiophosphate)-adenosine, 5′-O-(1-thiophosphate)-cytidine (α-thio-cytidine), 5′-O-(1-thiophosphate)-guanosine, 5′-O-(1-thiophosphate)-uridine, or 5′-O-(1-thiophosphate)-pseudouridine).

Other internucleoside linkages that may be employed according to the present invention, including internucleoside linkages which do not contain a phosphorous atom, are described herein.

In some embodiments, the sequence may include one or more cytotoxic nucleosides. For example, cytotoxic nucleosides may be incorporated into sequence, such as bifunctional modification. Cytotoxic nucleoside may include, but are not limited to, adenosine arabinoside, 5-azacytidine, 4′-thio-aracytidine, cyclopentenylcytosine, cladribine, clofarabine, cytarabine, cytosine arabinoside, 1-(2-C-cyano-2-deoxy-beta-D-arabino-pentofuranosyl)-cytosine, decitabine, 5-fluorouracil, fludarabine, floxuridine, gemcitabine, a combination of tegafur and uracil, tegafur ((RS)-5-fluoro-1-(tetrahydrofuran-2-yl)pyrimidine-2,4(1H,3H)-dione), troxacitabine, tezacitabine, 2′-deoxy-2′-methylidenecytidine (DMDC), and 6-mercaptopurine. Additional examples include fludarabine phosphate, N4-behenoyl-1-beta-D-arabinofuranosylcytosine, N4-octadecyl-1-beta-D-arabinofuranosylcytosine, N4-palmitoyl-1-(2-C-cyano-2-deoxy-beta-D-arabino-pentofuranosyl) cytosine, and P-4055 (cytarabine 5′-elaidic acid ester).

In some embodiments, the sequence includes one or more post-transcriptional modifications (e.g., capping, cleavage, polyadenylation, splicing, poly-A sequence, methylation, acylation, phosphorylation, methylation of lysine and arginine residues, acetylation, and nitrosylation of thiol groups and tyrosine residues, etc). The one or more post-transcriptional modifications can be any post-transcriptional modification, such as any of the more than one hundred different nucleoside modifications that have been identified in RNA (Rozenski, J, Crain, P, and McCloskey, J. (1999). The RNA Modification Database: 1999 update. Nucl Acids Res 27: 196-197) In some embodiments, the first isolated nucleic acid comprises messenger RNA (mRNA). In some embodiments, the mRNA comprises at least one nucleoside selected from the group consisting of pyridin-4-one ribonucleoside, 5-aza-uridine, 2-thio-5-aza-uridine, 2-thiouridine, 4-thio-pseudouridine, 2-thio-pseudouridine, 5-hydroxyuridine, 3-methyluridine, 5-carboxymethyl-uridine, 1-carboxymethyl-pseudouridine, 5-propynyl-uridine, 1-propynyl-pseudouridine, 5-taurinomethyluridine, 1-taurinomethyl-pseudouridine, 5-taurinomethyl-2-thio-uridine, 1-taurinomethyl-4-thio-uridine, 5-methyl-uridine, 1-methyl-pseudouridine, 4-thio-1-methyl-pseudouridine, 2-thio-1-methyl-pseudouridine, 1-methyl-1-deaza-pseudouridine, 2-thio-1-methyl-1-deaza-pseudouridine, dihydrouridine, dihydropseudouridine, 2-thio-dihydrouridine, 2-thio-dihydropseudouridine, 2-methoxyuridine, 2-methoxy-4-thio-uridine, 4-methoxy-pseudouridine, and 4-methoxy-2-thio-pseudouridine. In some embodiments, the mRNA comprises at least one nucleoside selected from the group consisting of 5-aza-cytidine, pseudoisocytidine, 3-methyl-cytidine, N4-acetylcytidine, 5-formylcytidine, N4-methylcytidine, 5-hydroxymethylcytidine, 1-methyl-pseudoisocytidine, pyrrolo-cytidine, pyrrolo-pseudoisocytidine, 2-thio-cytidine, 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, and 4-methoxy-1-methyl-pseudoisocytidine. In some embodiments, the mRNA comprises at least one nucleoside selected from the group consisting of 2-aminopurine, 2, 6-diaminopurine, 7-deaza-adenine, 7-deaza-8-aza-adenine, 7-deaza-2-aminopurine, 7-deaza-8-aza-2-aminopurine, 7-deaza-2,6-diaminopurine, 7-deaza-8-aza-2,6-diaminopurine, 1-methyladenosine, N6-methyladenosine, N6-isopentenyladenosine, N6-(cis-hydroxyisopentenyl)adenosine, 2-methylthio-N6-(cis-hydroxyisopentenyl) adenosine, N6-glycinylcarbamoyladenosine, N6-threonylcarbamoyladenosine, 2-methylthio-N6-threonyl carbamoyladenosine, N6,N6-dimethyladenosine, 7-methyladenine, 2-methylthio-adenine, and 2-methoxy-adenine. In some embodiments, mRNA comprises at least one nucleoside selected from the group consisting of inosine, 1-methyl-inosine, wyosine, wybutosine, 7-deaza-guanosine, 7-deaza-8-aza-guanosine, 6-thio-guanosine, 6-thio-7-deaza-guanosine, 6-thio-7-deaza-8-aza-guanosine, 7-methyl-guanosine, 6-thio-7-methyl-guanosine, 7-methylinosine, 6-methoxy-guanosine, 1-methylguanosine, N2-methylguanosine, N2,N2-dimethylguanosine, 8-oxo-guanosine, 7-methyl-8-oxo-guanosine, 1-methyl-6-thio-guanosine, N2-methyl-6-thio-guanosine, and N2,N2-dimethyl-6-thio-guanosine.

The sequence may or may not be uniformly modified along the entire length of the molecule. For example, one or more or all types of nucleotide (e.g., naturally-occurring nucleotides, purine or pyrimidine, or any one or more or all of A, G, U, C, I, pU) may or may not be uniformly modified in the sequence, or in a given predetermined sequence region thereof. In some embodiments, the sequence includes a pseudouridine. In some embodiments, the sequence includes an inosine, which may aid in the immune system characterizing the sequence as endogenous versus viral RNAs. The incorporation of inosine may also mediate improved RNA stability/reduced degradation. See for example, Yu, Z. et al. (2015) RNA editing by ADAR1 marks dsRNA as “self”. Cell Res. 25, 1283-1284, which is incorporated by reference in its entirety.

Cas12i Polypeptide

In some embodiments, the composition of the present invention includes a Cas12i polypeptide as described in PCT/US2019/022375.

In some embodiments, the composition of the present invention includes a Cas12i2 polypeptide described herein (e.g., a polypeptide comprising SEQ ID NO: 2634 and/or encoded by SEQ ID NO: 2633). In some embodiments, the Cas12i2 polypeptide comprises at least one RuvC domain.

A nucleic acid sequence encoding the Cas12i2 polypeptide described herein may be substantially identical to a reference nucleic acid sequence, e.g., SEQ ID NO: 2633. In some embodiments, the Cas12i2 polypeptide is encoded by a nucleic acid comprising a sequence having 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 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 99.5% sequence identity to the reference nucleic acid sequence, e.g., SEQ ID NO: 2633. The percent identity between two such nucleic acids can be determined manually by inspection of the two optimally aligned nucleic acid sequences or by using software programs or algorithms (e.g., BLAST, ALIGN, CLUSTAL) using standard parameters. One indication that two nucleic acid sequences are substantially identical is that the nucleic acid molecules hybridize to the complementary sequence of the other under stringent conditions of temperature and ionic strength (e.g., within a range of medium to high stringency). See, e.g., Tijssen, “Hybridization with Nucleic Acid Probes. Part I. Theory and Nucleic Acid Preparation” (Laboratory Techniques in Biochemistry and Molecular Biology, Vol 24).

In some embodiments, the Cas12i2 polypeptide is encoded by a nucleic acid sequence having 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 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or more sequence identity, but not 100% sequence identity, to a reference nucleic acid sequence, e.g., SEQ ID NO: 2633.

In some embodiments, the present invention describes a Cas12i2 polypeptide having a specified degree of amino acid sequence identity to one or more reference polypeptides, e.g., at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or even at least 99%, but not 100%, sequence identity to the amino acid sequence of SEQ ID NO: 2634. Homology or identity can be determined by amino acid sequence alignment, e.g., using a program such as BLAST, ALIGN, or CLUSTAL, as described herein.

Also provided is a Cas12i2 polypeptide of the present invention having enzymatic activity, e.g., nuclease or endonuclease activity, and comprising an amino acid sequence which differs from the amino acid sequences of SEQ ID NO: 2634 by 50, 40, 35, 30, 25, 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, 1, or 0 amino acid residue(s), when aligned using any of the previously described alignment methods.

In some embodiments, the Cas12i2 polypeptide comprises a polypeptide having a sequence of SEQ ID NO: 2641, SEQ ID NO: 2642, SEQ ID NO: 2643, SEQ ID NO: 2644, or SEQ ID NO: 2645.

In some embodiments, the Cas12i2 polypeptide of the present invention comprises a polypeptide sequence having at least 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 2641, SEQ ID NO: 2642, SEQ ID NO: 2643, SEQ ID NO: 2644, or SEQ ID NO: 2645. In some embodiments, a Cas12i2 polypeptide having at least 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 2641, SEQ ID NO: 2642, SEQ ID NO: 2643, SEQ ID NO: 2644, or SEQ ID NO: 2645 maintains the amino acid changes (or at least 1, 2, 3 etc. of these changes) that differentiate it from its respective parent/reference sequence.

In some embodiments, the present invention describes a Cas12i2 polypeptide having a specified degree of amino acid sequence identity to one or more reference polypeptides, e.g., at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or even at least 99%, but not 100%, sequence identity to the amino acid sequence of SEQ ID NO: 2641, SEQ ID NO: 2642, SEQ ID NO: 2643, SEQ ID NO: 2644, or SEQ ID NO: 2645. Homology or identity can be determined by amino acid sequence alignment, e.g., using a program such as BLAST, ALIGN, or CLUSTAL, as described herein.

Also provided is a Cas12i2 polypeptide of the present invention having enzymatic activity, e.g., nuclease or endonuclease activity, and comprising an amino acid sequence which differs from the amino acid sequences of SEQ ID NO: 2641, SEQ ID NO: 2642, SEQ ID NO: 2643, SEQ ID NO: 2644, or SEQ ID NO: 2645 by 50, 40, 35, 30, 25, 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, 1, or 0 amino acid residue(s), when aligned using any of the previously described alignment methods.

In some embodiments, the composition of the present invention includes a Cas12i4 polypeptide described herein (e.g., a polypeptide comprising SEQ ID NO: 2647 and/or encoded by SEQ ID NO: 2646). In some embodiments, the Cas12i4 polypeptide comprises at least one RuvC domain.

A nucleic acid sequence encoding the Cas12i4 polypeptide described herein may be substantially identical to a reference nucleic acid sequence, e.g., SEQ ID NO: 2646. In some embodiments, the Cas12i4 polypeptide is encoded by a nucleic acid comprising a sequence having 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 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 99.5% sequence identity to the reference nucleic acid sequence, e.g., SEQ ID NO: 2646. The percent identity between two such nucleic acids can be determined manually by inspection of the two optimally aligned nucleic acid sequences or by using software programs or algorithms (e.g., BLAST, ALIGN, CLUSTAL) using standard parameters. One indication that two nucleic acid sequences are substantially identical is that the nucleic acid molecules hybridize to the complementary sequence of the other under stringent conditions of temperature and ionic strength (e.g., within a range of medium to high stringency).

In some embodiments, the Cas12i4 polypeptide is encoded by a nucleic acid sequence having 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 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or more sequence identity, but not 100% sequence identity, to a reference nucleic acid sequence, e.g., SEQ ID NO: 2646.

In some embodiments, the present invention describes a Cas12i4 polypeptide having a specified degree of amino acid sequence identity to one or more reference polypeptides, e.g., at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or even at least 99%, but not 100%, sequence identity to the amino acid sequence of SEQ ID NO: 2647. Homology or identity can be determined by amino acid sequence alignment, e.g., using a program such as BLAST, ALIGN, or CLUSTAL, as described herein.

Also provided is a Cas12i4 polypeptide of the present invention having enzymatic activity, e.g., nuclease or endonuclease activity, and comprising an amino acid sequence which differs from the amino acid sequences of SEQ ID NO: 2647 by 50, 40, 35, 30, 25, 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, 1, or 0 amino acid residue(s), when aligned using any of the previously described alignment methods.

In some embodiments, the Cas12i4 polypeptide comprises a polypeptide having a sequence of SEQ ID NO: 2648 or SEQ ID NO: 2649.

In some embodiments, the Cas12i4 polypeptide of the present invention comprises a polypeptide sequence having at least 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 2648 or SEQ ID NO: 2649. In some embodiments, a Cas12i4 polypeptide having at least 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 2648 or SEQ ID NO: 2649 maintains the amino acid changes (or at least 1, 2, 3 etc, of these changes) that differentiate it from its respective parent/reference sequence.

In some embodiments, the present invention describes a Cas12i4 polypeptide having a specified degree of amino acid sequence identity to one or more reference polypeptides, e.g., at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or even at least 99%, but not 100%, sequence identity to the amino acid sequence of SEQ ID NO: 2648 or SEQ ID NO: 2649. Homology or identity can be determined by amino acid sequence alignment, e.g., using a program such as BLAST, ALIGN, or CLUSTAL, as described herein.

Also provided is a Cas12i4 polypeptide of the present invention having enzymatic activity, e.g., nuclease or endonuclease activity, and comprising an amino acid sequence which differs from the amino acid sequences of SEQ ID NO: 2648 or SEQ ID NO: 2649 by 50, 40, 35, 30, 25, 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, 1, or 0 amino acid residue(s), when aligned using any of the previously described alignment methods.

In some embodiments, the composition of the present invention includes a Cas12i1 polypeptide described herein (e.g., a polypeptide comprising SEQ ID NO: 2650). In some embodiments, the Cas12i4 polypeptide comprises at least one RuvC domain.

In some embodiments, the Cas12i1 polypeptide of the present invention comprises a polypeptide sequence having at least 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 2650.

In some embodiments, the present invention describes a Cas12i1 polypeptide having a specified degree of amino acid sequence identity to one or more reference polypeptides, e.g., at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or even at least 99%, but not 100%, sequence identity to the amino acid sequence of SEQ ID NO: 2650. Homology or identity can be determined by amino acid sequence alignment, e.g., using a program such as BLAST, ALIGN, or CLUSTAL, as described herein.

Also provided is a Cas12i1 polypeptide of the present invention having enzymatic activity, e.g., nuclease or endonuclease activity, and comprising an amino acid sequence which differs from the amino acid sequences of SEQ ID NO: 2650 by 50, 40, 35, 30, 25, 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, 1, or 0 amino acid residue(s), when aligned using any of the previously described alignment methods.

In some embodiments, the composition of the present invention includes a Cas12i3 polypeptide described herein (e.g., a polypeptide comprising SEQ ID NO: 2651). In some embodiments, the Cas12i4 polypeptide comprises at least one RuvC domain.

In some embodiments, the Cas12i3 polypeptide of the present invention comprises a polypeptide sequence having at least 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 2651.

In some embodiments, the present invention describes a Cas12i3 polypeptide having a specified degree of amino acid sequence identity to one or more reference polypeptides, e.g., at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or even at least 99%, but not 100%, sequence identity to the amino acid sequence of SEQ ID NO: 2651. Homology or identity can be determined by amino acid sequence alignment, e.g., using a program such as BLAST, ALIGN, or CLUSTAL, as described herein.

Also provided is a Cas12i3 polypeptide of the present invention having enzymatic activity, e.g., nuclease or endonuclease activity, and comprising an amino acid sequence which differs from the amino acid sequences of SEQ ID NO: 2651 by 50, 40, 35, 30, 25, 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, 1, or 0 amino acid residue(s), when aligned using any of the previously described alignment methods.

Although the changes described herein may be one or more amino acid changes, changes to the Cas12i polypeptide may also be of a substantive nature, such as fusion of polypeptides as amino- and/or carboxyl-terminal extensions. For example, the Cas12i polypeptide may contain additional peptides, e.g., one or more peptides. Examples of additional peptides may include epitope peptides for labelling, such as a polyhistidine tag (His-tag), Myc, and FLAG. In some embodiments, the Cas12i polypeptide described herein can be fused to a detectable moiety such as a fluorescent protein (e.g., green fluorescent protein (GFP) or yellow fluorescent protein (YFP)).

In some embodiments, the Cas12i polypeptide comprises at least one (e.g., two, three, four, five, six, or more) nuclear localization signal (NLS). In some embodiments, the Cas12i polypeptide comprises at least one (e.g., two, three, four, five, six, or more) nuclear export signal (NES). In some embodiments, the Cas12i polypeptide comprises at least one (e.g., two, three, four, five, six, or more) NLS and at least one (e.g., two, three, four, five, six, or more) NES.

In some embodiments, the Cas12i polypeptide described herein can be self-inactivating. See, Epstein et al., “Engineering a Self-Inactivating CRISPR System for AAV Vectors,” Mol. Ther., 24 (2016): S50, which is incorporated by reference in its entirety.

In some embodiments, the nucleotide sequence encoding the Cas12i polypeptide described herein can be codon-optimized for use in a particular host cell or organism. For example, the nucleic acid can be codon-optimized for any non-human eukaryote including mice, rats, rabbits, dogs, livestock, or non-human primates. Codon usage tables are readily available, for example, at the “Codon Usage Database” available at www.kazusa.orjp/codon/and these tables can be adapted in a number of ways. See Nakamura et al. Nucl. Acids Res. 28:292 (2000), which is incorporated herein by reference in its entirety. Computer algorithms for codon optimizing a particular sequence for expression in a particular host cell are also available, such as Gene Forge (Aptagen; Jacobus, PA).

Target Sequence

In some embodiments, the target sequence is within a BCL11A gene or a locus of a BCL11A gene. In some embodiments, the BCL11A gene is a mammalian gene. In some embodiments, the BCL11A gene is a human gene. For example, in some embodiments, the target sequence is within the sequence of SEQ ID NO: 2635 or the reverse complement thereof. In some embodiments, the target sequence is within an exon or enhancer region of the BCL11A gene set forth in SEQ ID NO: 2635 (or the reverse complement thereof), e.g., within a sequence of SEQ ID NO: 2636, 2637, 2638, 2639, or 2640 (or a reverse complement thereof). Target sequences within an exon or enhancer region of the BCL11A gene of SEQ ID NO: 2635 (and the reverse complement thereof) are set forth in Table 5. In some embodiments, the target sequence is within an intron of the BCL11A gene set forth in SEQ ID NO: 2635 or the reverse complement thereof. In some embodiments, the target sequence is within a variant (e.g., a polymorphic variant) of the BCL11A gene sequence set forth in SEQ ID NO: 2635 or the reverse complement thereof. In some embodiments, the BCL11A gene sequence is a homolog of the sequence set forth in SEQ ID NO: 2635 or the reverse complement thereof. For examples, in some embodiments, the BCL11A gene sequence is a non-human BCL11A sequence.

In some embodiments, the target sequence is adjacent to a 5′-NTTN-3′ PAM sequence, wherein N is any nucleotide. The 5′-NTTN-3′ sequence may be immediately adjacent to the target sequence or, for example, within a small number (e.g., 1, 2, 3, 4, or 5) of nucleotides of the target sequence. In some embodiments the 5′-NTTN-3′ sequence is 5′-NTTY-3′, 5′-NTTC-3′, 5′-NTTT-3′, 5′-NTTA-3′, 5′-NTTB-3′, 5′-NTTG-3′, 5′-CTTY-3′, 5‘-DTTR’3′, 5′-CTTR-3′, 5′-DTTT-3′, 5′-ATTN-3′, or 5′-GTTN-3′, wherein Y is C or T, B is any nucleotide except for A, D is any nucleotide except for C, and R is A or G. In some embodiments, the 5′-NTTN-3′ sequence is 5′-ATTA-3′, 5′-ATTT-3′, 5′-ATTG-3′, 5′-ATTC-3′, 5′-TTTA-3′, 5′-TTTT-3′, 5′-TTTG-3′, 5′-TTTC-3′, 5′-GTTA-3′, 5′-GTTT-3′, 5′-GTTG-3′, 5′-GTTC-3′, 5′-CTTA-3′, 5′-CTTT-3′, 5′-CTTG-3′, or 5′-CTTC-3′.

In some embodiments, the target sequence is single-stranded (e.g., single-stranded DNA). In some embodiments, the target sequence is double-stranded (e.g., double-stranded DNA). In some embodiments, the target sequence comprises both single-stranded and double-stranded regions. In some embodiments, the target sequence is linear. In some embodiments, the target sequence is circular. In some embodiments, the target sequence comprises one or more modified nucleotides, such as methylated nucleotides, damaged nucleotides, or nucleotides analogs. In some embodiments, the target sequence is not modified. In some embodiments, the RNA guide binds to a first strand of a double-stranded target sequence (e.g., the target strand or the spacer-complementary strand), and the 5′-NTTN-3′ PAM sequence is present in the second, complementary strand (e.g., the non-target strand or the non-spacer-complementary strand). In some embodiments, the RNA guide binds adjacent to a 5′-NAAN-3′ sequence on the target strand (e.g., the spacer-complementary strand).

In some embodiments, the target sequence is present in a cell. In some embodiments, the target sequence is present in the nucleus of the cell. In some embodiments, the target sequence is endogenous to the cell. In some embodiments, the target sequence is a genomic DNA. In some embodiments, the target sequence is a chromosomal DNA. In some embodiments, the target sequence is a protein-coding gene or a functional region thereof, such as a coding region, or a regulatory element, such as a promoter, enhancer, a 5′ or 3′ untranslated region, etc. In some embodiments, the target sequence is a plasmid.

In some embodiments, the target sequence is present in a readily accessible region of the target sequence. In some embodiments, the target sequence is in an exon of a target gene. In some embodiments, the target sequence is across an exon-intron junction of a target gene. In some embodiments, the target sequence is present in a non-coding region, such as a regulatory region of a gene. In some embodiments, wherein the target sequence is exogenous to a cell, the target sequence comprises a sequence that is not found in the genome of the cell.

In some embodiments, the target sequence is exogenous to a cell. In some embodiments, the target sequence is a horizontally transferred plasmid. In some embodiments, the target sequence is integrated in the genome of the cell. In some embodiments, the target sequence is not integrated in the genome of the cell. In some embodiments, the target sequence is a plasmid in the cell. In some embodiments, the target sequence is present in an extrachromosomal array.

In some embodiments, the target sequence is an isolated nucleic acid, such as an isolated DNA or an isolated RNA. In some embodiments, the target sequence is present in a cell-free environment. In some embodiments, the target sequence is an isolated vector, such as a plasmid. In some embodiments, the target sequence is an ultrapure plasmid.

The target sequence is a locus of the BCL11A gene that hybridizes to the RNA guide. In some embodiments, a cell has only one copy of the target sequence. In some embodiments, a cell has more than one copy, such as at least about any one of 2, 3, 4, 5, 10, 100, or more copies of the target sequence.

In some embodiments, a BCL11A target sequence is selected to be edited by a Cas12i polypeptide and an RNA guide using one or more of the following criteria. First, in some embodiments, a target sequence near the 5′ end of the BCL11A coding sequence is selected. For example, in some embodiments, an RNA guide is designed to target a sequence in exon 1 (SEQ ID NO: 2636), exon 2 (SEQ ID NO: 2637), or the enhancer region (SEQ ID NO: 2640). Second, in some embodiments, a target sequence adjacent to a 5′-CTTY-3′ PAM sequence is selected. For example, in some embodiments, an RNA guide is designed to target a sequence adjacent to a 5′-CTTT-3′ or 5′-CTTC-3′ sequence. Third, in some embodiments, a target sequence having low sequence similarity to other genomic sequences is selected. For example, for each target sequence, potential non-target sites can be identified by searching for other genomic sequences adjacent to a PAM sequence and calculating the Levenshtein distance between the target sequence and the PAM-adjacent sequences. The Levenshtein distance (e.g., edit distance) corresponds to the minimum number of edits (e.g., insertions, deletions, or substitutions) required to change one sequence into another (e.g., to change the sequence of a potential non-target locus into the sequence of the on-target locus). Following this analysis, RNA guides are designed for target sequences that do not have potential off-target sequences with a Levenshtein distance of 0 or 1.

Production

The present invention includes methods for production of the RNA guide, methods for production of the Cas12i polypeptide, and methods for complexing the RNA guide and Cas12i polypeptide.

RNA Guide

In some embodiments, the RNA guide is made by in vitro transcription of a DNA template. Thus, for example, in some embodiments, the RNA guide is generated by in vitro transcription of a DNA template encoding the RNA guide using an upstream promoter sequence (e.g., a T7 polymerase promoter sequence). In some embodiments, the DNA template encodes multiple RNA guides or the in vitro transcription reaction includes multiple different DNA templates, each encoding a different RNA guide. In some embodiments, the RNA guide is made using chemical synthetic methods. In some embodiments, the RNA guide is made by expressing the RNA guide sequence in cells transfected with a plasmid including sequences that encode the RNA guide. In some embodiments, the plasmid encodes multiple different RNA guides. In some embodiments, multiple different plasmids, each encoding a different RNA guide, are transfected into the cells. In some embodiments, the RNA guide is expressed from a plasmid that encodes the RNA guide and also encodes a Cas12i polypeptide. In some embodiments, the RNA guide is expressed from a plasmid that expresses the RNA guide but not a Cas12i polypeptide. In some embodiments, the RNA guide is purchased from a commercial vendor. In some embodiments, the RNA guide is synthesized using one or more modified nucleotide, e.g., as described above.

Cas12i Polypeptide

In some embodiments, the Cas12i polypeptide of the present invention can be prepared by (a) culturing bacteria which produce the Cas12i polypeptide of the present invention, isolating the Cas12i polypeptide, optionally, purifying the Cas12i polypeptide, and complexing the Cas12i polypeptide with an RNA guide. The Cas12i polypeptide can be also prepared by (b) a known genetic engineering technique, specifically, by isolating a gene encoding the Cas12i polypeptide of the present invention from bacteria, constructing a recombinant expression vector, and then transferring the vector into an appropriate host cell that expresses the RNA guide for expression of a recombinant protein that complexes with the RNA guide in the host cell. Alternatively, the Cas12i polypeptide can be prepared by (c) an in vitro coupled transcription-translation system and then complexing with an RNA guide.

In some embodiments, a host cell is used to express the Cas12i polypeptide. The host cell is not particularly limited, and various known cells can be preferably used. Specific examples of the host cell include bacteria such as E. coli, yeasts (budding yeast, Saccharomyces cerevisiae, and fission yeast, Schizosaccharomyces pombe), nematodes (Caenorhabditis elegans), Xenopus laevis oocytes, and animal cells (for example, CHO cells, COS cells and HEK293 cells). The method for transferring the expression vector described above into host cells, i.e., the transformation method, is not particularly limited, and known methods such as electroporation, the calcium phosphate method, the liposome method and the DEAE dextran method can be used.

After a host is transformed with the expression vector, the host cells may be cultured, cultivated or bred, for production of the Cas12i polypeptide. After expression of the Cas12i polypeptide, the host cells can be collected and Cas12i polypeptide purified from the cultures etc. according to conventional methods (for example, filtration, centrifugation, cell disruption, gel filtration chromatography, ion exchange chromatography, etc.).

In some embodiments, the methods for Cas12i polypeptide expression comprises translation of at least 5 amino acids, at least 10 amino acids, at least 15 amino acids, at least 20 amino acids, at least 50 amino acids, at least 100 amino acids, at least 150 amino acids, at least 200 amino acids, at least 250 amino acids, at least 300 amino acids, at least 400 amino acids, at least 500 amino acids, at least 600 amino acids, at least 700 amino acids, at least 800 amino acids, at least 900 amino acids, or at least 1000 amino acids of the Cas12i polypeptide.

In some embodiments, the methods for protein expression comprises translation of about 5 amino acids, about 10 amino acids, about 15 amino acids, about 20 amino acids, about 50 amino acids, about 100 amino acids, about 150 amino acids, about 200 amino acids, about 250 amino acids, about 300 amino acids, about 400 amino acids, about 500 amino acids, about 600 amino acids, about 700 amino acids, about 800 amino acids, about 900 amino acids, about 1000 amino acids or more of the Cas12i polypeptide.

A variety of methods can be used to determine the level of production of a Cas12i polypeptide in a host cell. Such methods include, but are not limited to, for example, methods that utilize either polyclonal or monoclonal antibodies specific for the Cas12i polypeptide or a labeling tag as described elsewhere herein. Exemplary methods include, but are not limited to, enzyme-linked immunosorbent assays (ELISA), radioimmunoassays (MA), fluorescent immunoassays (FIA), and fluorescent activated cell sorting (FACS). These and other assays are well known in the art (See, e.g., Maddox et al., J. Exp. Med. 158:1211 [1983]).

The present disclosure provides methods of in vivo expression of the Cas12i polypeptide in a cell, comprising providing a polyribonucleotide encoding the Cas12i polypeptide to a host cell wherein the polyribonucleotide encodes the Cas12i polypeptide, expressing the Cas12i polypeptide in the cell, and obtaining the Cas12i polypeptide from the cell.

Complexing

In some embodiments, an RNA guide targeting BCL11A is complexed with a Cas12i polypeptide to form a ribonucleoprotein. In some embodiments, complexation of the RNA guide and Cas12i polypeptide occurs at a temperature lower than about any one of 20° C., 21° C., 22° C., 23° C., 24° C., 25° C., 26° C., 27° C., 28° C., 29° C., 30° C., 31° C., 32° C., 33° C., 34° C., 35° C., 36° C., 37° C., 38° C., 39° C., 40° C., 41° C., 42° C., 43° C., 44° C., 45° C., 50° C., or 55° C. In some embodiments, the RNA guide does not dissociate from the Cas12i polypeptide at about 37° C. over an incubation period of at least about any one of 10 mins, 15 mins, 20 mins, 25 mins, 30 mins, 35 mins, 40 mins, 45 mins, 50 mins, 55 mins, 1 hr, 2 hr, 3 hr, 4 hr, or more hours.

In some embodiments, the RNA guide and Cas12i polypeptide are complexed in a complexation buffer. In some embodiments, the Cas12i polypeptide is stored in a buffer that is replaced with a complexation buffer to form a complex with the RNA guide. In some embodiments, the Cas12i polypeptide is stored in a complexation buffer.

In some embodiments, the complexation buffer has a pH in a range of about 7.3 to 8.6. In one embodiment, the pH of the complexation buffer is about 7.3. In one embodiment, the pH of the complexation buffer is about 7.4. In one embodiment, the pH of the complexation buffer is about 7.5. In one embodiment, the pH of the complexation buffer is about 7.6. In one embodiment, the pH of the complexation buffer is about 7.7. In one embodiment, the pH of the complexation buffer is about 7.8. In one embodiment, the pH of the complexation buffer is about 7.9. In one embodiment, the pH of the complexation buffer is about 8.0. In one embodiment, the pH of the complexation buffer is about 8.1. In one embodiment, the pH of the complexation buffer is about 8.2. In one embodiment, the pH of the complexation buffer is about 8.3. In one embodiment, the pH of the complexation buffer is about 8.4. In one embodiment, the pH of the complexation buffer is about 8.5. In one embodiment, the pH of the complexation buffer is about 8.6.

In some embodiments, the Cas12i polypeptide can be overexpressed and complexed with the RNA guide in a host cell prior to purification as described herein. In some embodiments, mRNA or DNA encoding the Cas12i polypeptide is introduced into a cell so that the Cas12i polypeptide is expressed in the cell. In some embodiments, the RNA guide is also introduced into the cell, whether simultaneously, separately, or sequentially from a single mRNA or DNA construct, such that the ribonucleoprotein complex is formed in the cell.

Delivery

Compositions or complexes described herein may be formulated, for example, including a carrier, such as a carrier and/or a polymeric carrier, e.g., a liposome, and delivered by known methods to a cell (e.g., a prokaryotic, eukaryotic, plant, mammalian, etc.). Such methods include, but not limited to, transfection (e.g., lipid-mediated, cationic polymers, calcium phosphate, dendrimers); electroporation or other methods of membrane disruption (e.g., nucleofection), viral delivery (e.g., lentivirus, retrovirus, adenovirus, AAV), microinjection, microprojectile bombardment (“gene gun”), fugene, direct sonic loading, cell squeezing, optical transfection, protoplast fusion, impalefection, magnetofection, exosome-mediated transfer, lipid nanoparticle-mediated transfer, and any combination thereof.

In some embodiments, the method comprises delivering one or more nucleic acids (e.g., nucleic acids encoding the Cas12i polypeptide, RNA guide, donor DNA, etc.), one or more transcripts thereof, and/or a pre-formed RNA guide/Cas12i polypeptide complex to a cell, where a ternary complex is formed. Exemplary intracellular delivery methods, include, but are not limited to: viruses or virus-like agents; chemical-based transfection methods, such as those using calcium phosphate, dendrimers, liposomes, or cationic polymers (e.g., DEAE-dextran or polyethylenimine); non-chemical methods, such as microinjection, electroporation, cell squeezing, sonoporation, optical transfection, impalefection, protoplast fusion, bacterial conjugation, delivery of plasmids or transposons; particle-based methods, such as using a gene gun, magnectofection or magnet assisted transfection, particle bombardment; and hybrid methods, such as nucleofection. In some embodiments, the present application further provides cells produced by such methods, and organisms (such as animals, plants, or fungi) comprising or produced from such cells.

In some embodiments, the Cas12i component and the RNA guide component are delivered together. For example, in some embodiments, the Cas12i component and the RNA guide component are packaged together in a single AAV particle. In another example, in some embodiments, the Cas12i component and the RNA guide component are delivered together via lipid nanoparticles (LNPs). In some embodiments, the Cas12i component and the RNA guide component are delivered separately. For example, in some embodiments, the Cas12i component and the RNA guide are packaged into separate AAV particles. In another example, in some embodiments, the Cas12i component is delivered by a first delivery mechanism and the RNA guide is delivered by a second delivery mechanism.

Cells

Compositions or complexes described herein can be delivered to a variety of cells. In some embodiments, the cell is an isolated cell. In some embodiments, the cell is in cell culture or a co-culture of two or more cell types. In some embodiments, the cell is ex vivo. In some embodiments, the cell is obtained from a living organism and maintained in a cell culture. In some embodiments, the cell is a single-cellular organism.

In some embodiments, the cell is a prokaryotic cell. In some embodiments, the cell is a bacterial cell or derived from a bacterial cell. In some embodiments, the cell is an archaeal cell or derived from an archaeal cell.

In some embodiments, the cell is a eukaryotic cell. In some embodiments, the cell is a plant cell or derived from a plant cell. In some embodiments, the cell is a fungal cell or derived from a fungal cell. In some embodiments, the cell is an animal cell or derived from an animal cell. In some embodiments, the cell is an invertebrate cell or derived from an invertebrate cell. In some embodiments, the cell is a vertebrate cell or derived from a vertebrate cell. In some embodiments, the cell is a mammalian cell or derived from a mammalian cell. In some embodiments, the cell is a human cell. In some embodiments, the cell is a zebra fish cell. In some embodiments, the cell is a rodent cell. In some embodiments, the cell is synthetically made, sometimes termed an artificial cell.

In some embodiments, the cell is derived from a cell line. A wide variety of cell lines for tissue culture are known in the art. Examples of cell lines include, but are not limited to, 293T, MF7, K562, HeLa, CHO, and transgenic varieties thereof. Cell lines are available from a variety of sources known to those with skill in the art (see, e.g., the American Type Culture Collection (ATCC) (Manassas, Va.)). In some embodiments, the cell is an immortal or immortalized cell.

In some embodiments, the cell is a primary cell. In some embodiments, the cell is a stem cell such as a totipotent stem cell (e.g., omnipotent), a pluripotent stem cell, a multipotent stem cell, an oligopotent stem cell, or an unipotent stem cell. In some embodiments, the cell is an induced pluripotent stem cell (iPSC) or derived from an iPSC. In some embodiments, the cell is a differentiated cell. For example, in some embodiments, the differentiated cell is a muscle cell (e.g., a myocyte), a fat cell (e.g., an adipocyte), a bone cell (e.g., an osteoblast, osteocyte, osteoclast), a blood cell (e.g., a monocyte, a lymphocyte, a neutrophil, an eosinophil, a basophil, a macrophage, a erythrocyte, or a platelet), a nerve cell (e.g., a neuron), an epithelial cell, an immune cell (e.g., a lymphocyte, a neutrophil, a monocyte, or a macrophage), a liver cell (e.g., a hepatocyte), a fibroblast, or a sex cell. In some embodiments, the cell is a terminally differentiated cell. For example, in some embodiments, the terminally differentiated cell is a neuronal cell, an adipocyte, a cardiomyocyte, a skeletal muscle cell, an epidermal cell, or a gut cell. In some embodiments, the cell is an immune cell. In some embodiments, the immune cell is a T cell. In some embodiments, the immune cell is a B cell. In some embodiments, the immune cell is a Natural Killer (NK) cell. In some embodiments, the immune cell is a Tumor Infiltrating Lymphocyte (TIL). In some embodiments, the cell is a mammalian cell, e.g., a human cell or a murine cell. In some embodiments, the murine cell is derived from a wild-type mouse, an immunosuppressed mouse, or a disease-specific mouse model. In some embodiments, the cell is a cell within a living tissue, organ, or organism.

Methods

The disclosure also provides methods of modifying a target sequence within the BCL11A gene. In some embodiments, the methods comprise introducing a BCL11A-targeting RNA guide and a Cas12i polypeptide into a cell. The BCL11A-targeting RNA guide and Cas12i polypeptide can be introduced as a ribonucleoprotein complex into a cell. The BCL11A-targeting RNA guide and Cas12i polypeptide can be introduced on a nucleic acid vector. The Cas12i polypeptide can be introduced as an mRNA. The RNA guide can be introduced directly into the cell.

In some embodiments, the sequence of the BCL11A gene is set forth in SEQ ID NO: 2635 or the reverse complement thereof. In some embodiments, the target sequence is in an exon of a BCL11A gene, such as an exon having a sequence set forth in any one of SEQ ID NO: 2636, SEQ ID NO: 2637, SEQ ID NO: 2638, or SEQ ID NO: 2639, or a reverse complement thereof, or in an enhancer region of the BCL11A gene, such as an enhancer region having a sequence set forth in SEQ ID NO: 2640, or the reverse complement thereof. In some embodiments, the target sequence is in an intron of a BCL11A gene (e.g., an intron of the sequence set forth in SEQ ID NO: 2635 or the reverse complement thereof). In other embodiments, the sequence of the BCL11A gene is a variant of the sequence set forth in SEQ ID NO: 2635 (or the reverse complement thereof) or a homolog of the sequence set forth in SEQ ID NO: 2635 (or the reverse complement thereof). For example, in some embodiments, the target sequence is polymorphic variant of the BCL11A sequence set forth in SEQ ID NO: 2635 (or the reverse complement thereof) or a non-human form of the BCL11A gene.

In some embodiments, an RNA guide as disclosed herein is designed to be complementary to a target sequence that is adjacent to a 5′-NTTN-3′ PAM sequence. The 5′-NTTN-3′ sequence may be immediately adjacent to the target sequence or, for example, within a small number (e.g., 1, 2, 3, 4, or 5) of nucleotides of the target sequence. In some embodiments the 5′-NTTN-3′ sequence is 5′-NTTY-3′, 5′-NTTC-3′, 5′-NTTT-3′, 5′-NTTA-3′, 5′-NTTB-3′, 5′-NTTG-3′, 5′-CTTY-3′, 5‘-DTTR’3′, 5′-CTTR-3′, 5′-DTTT-3′, 5′-ATTN-3′, or 5′-GTTN-3′, wherein Y is C or T, B is any nucleotide except for A, D is any nucleotide except for C, and R is A or G. In some embodiments, the 5′-NTTN-3′ sequence is 5′-ATTA-3′, 5′-ATTT-3′, 5′-ATTG-3′, 5′-ATTC-3′, 5′-TTTA-3′, 5′-TTTT-3′, 5′-TTTG-3′, 5′-TTTC-3′, 5′-GTTA-3′, 5′-GTTT-3′, 5′-GTTG-3′, 5′-GTTC-3′, 5′-CTTA-3′, 5′-CTTT-3′, 5′-CTTG-3′, or 5′-CTTC-3′. In some embodiments, the RNA guide is designed to bind to a first strand of a double-stranded target sequence (e.g., the target strand or the spacer-complementary strand), and the 5′-NTTN-3′ PAM sequence is present in the second, complementary strand (e.g., the non-target strand or the non-spacer-complementary strand). In some embodiments, the RNA guide binds adjacent to a 5′-NAAN-3′ sequence on the target strand (e.g., the spacer-complementary strand).

In some embodiments, the Cas12i polypeptide has enzymatic activity (e.g., nuclease activity). In some embodiments, the Cas12i polypeptide induces one or more DNA double-stranded breaks in the cell. In some embodiments, the Cas12i polypeptide induces one or more DNA single-stranded breaks in the cell. In some embodiments, the Cas12i polypeptide induces one or more DNA nicks in the cell. In some embodiments, DNA breaks and/or nicks result in formation of one or more indels (e.g., one or more deletions).

In some embodiments, an RNA guide disclosed herein forms a complex with the Cas12i polypeptide and directs the Cas12i polypeptide to a target sequence adjacent to a 5′-NTTN-3′ sequence. In some embodiments, the complex induces a deletion (e.g., a nucleotide deletion or DNA deletion) adjacent to the 5′-NTTN-3′ sequence. In some embodiments, the complex induces a deletion adjacent to a 5′-ATTA-3′, 5′-ATTT-3′, 5′-ATTG-3′, 5′-ATTC-3′, 5′-TTTA-3′, 5′-TTTT-3′, 5′-TTTG-3′, 5′-TTTC-3′, 5′-GTTA-3′, 5′-GTTT-3′, 5′-GTTG-3′, 5′-GTTC-3′, 5′-CTTA-3′, 5′-CTTT-3′, 5′-CTTG-3′, or 5′-CTTC-3′ sequence. In some embodiments, the complex induces a deletion adjacent to a T/C-rich sequence.

In some embodiments, the deletion is downstream of a 5′-NTTN-3′ sequence. In some embodiments, the deletion is downstream of a 5′-ATTA-3′, 5′-ATTT-3′, 5′-ATTG-3′, 5′-ATTC-3′, 5′-TTTA-3′, 5′-TTTT-3′, 5′-TTTG-3′, 5′-TTTC-3′, 5′-GTTA-3′, 5′-GTTT-3′, 5′-GTTG-3′, 5′-GTTC-3′, 5′-CTTA-3′, 5′-CTTT-3′, 5′-CTTG-3′, or 5′-CTTC-3′ sequence. In some embodiments, the deletion is downstream of a T/C-rich sequence.

In some embodiments, the deletion alters expression of the BCL11A gene. In some embodiments, the deletion alters function of the BCL11A gene. In some embodiments, the deletion inactivates the BCL11A gene. In some embodiments, the deletion is a frameshifting deletion. In some embodiments, the deletion is a non-frameshifting deletion. In some embodiments, the deletion leads to cell toxicity or cell death (e.g., apoptosis).

In some embodiments, the deletion starts within about 5 to about 15 nucleotides (e.g., about 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 nucleotides) of the 5′-NTTN-3′ sequence. In some embodiments, the deletion starts within about 5 to about 15 nucleotides (e.g., about 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 nucleotides) of a 5′-ATTA-3′, 5′-ATTT-3′, 5′-ATTG-3′, 5′-ATTC-3′, 5′-TTTA-3′, 5′-TTTT-3′, 5′-TTTG-3′, 5′-TTTC-3′, 5′-GTTA-3′, 5′-GTTT-3′, 5′-GTTG-3′, 5′-GTTC-3′, 5′-CTTA-3′, 5′-CTTT-3′, 5′-CTTG-3′, or 5′-CTTC-3′ sequence. In some embodiments, the deletion starts within about 5 to about 15 nucleotides (e.g., about 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 nucleotides) of a T/C-rich sequence.

In some embodiments, the deletion starts within about 5 to about 15 nucleotides (e.g., about 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 nucleotides) downstream of the 5′-NTTN-3′ sequence. In some embodiments, the deletion starts within about 5 to about 15 nucleotides (e.g., about 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 nucleotides) downstream of a 5′-ATTA-3′, 5′-ATTT-3′, 5′-ATTG-3′, 5′-ATTC-3′, 5′-TTTA-3′, 5′-TTTT-3′, 5′-TTTG-3′, 5′-TTTC-3′, 5′-GTTA-3′, 5′-GTTT-3′, 5′-GTTG-3′, 5′-GTTC-3′, 5′-CTTA-3′, 5′-CTTT-3′, 5′-CTTG-3′, or 5′-CTTC-3′ sequence. In some embodiments, the deletion starts within about 5 to about 15 nucleotides (e.g., about 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 nucleotides) downstream of a T/C-rich sequence.

In some embodiments, the deletion starts within about 5 to about 10 nucleotides (e.g., about 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 nucleotides) of the 5′-NTTN-3′ sequence. In some embodiments, the deletion starts within about 5 to about 10 nucleotides (e.g., about 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 nucleotides) of a 5′-ATTA-3′, 5′-ATTT-3′, 5′-ATTG-3′, 5′-ATTC-3′, 5′-TTTA-3′, 5′-TTTT-3′, 5′-TTTG-3′, 5′-TTTC-3′, 5′-GTTA-3′, 5′-GTTT-3′, 5′-GTTG-3′, 5′-GTTC-3′, 5′-CTTA-3′, 5′-CTTT-3′, 5′-CTTG-3′, or 5′-CTTC-3′ sequence. In some embodiments, the deletion starts within about 5 to about 10 nucleotides (e.g., about 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 nucleotides) of a T/C-rich sequence.

In some embodiments, the deletion starts within about 5 to about 10 nucleotides (e.g., about 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 nucleotides) downstream of the 5′-NTTN-3′ sequence. In some embodiments, the deletion starts within about 5 to about 10 nucleotides (e.g., about 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 nucleotides) downstream of a 5′-ATTA-3′, 5′-ATTT-3′, 5′-ATTG-3′, 5′-ATTC-3′, 5′-TTTA-3′, 5′-TTTT-3′, 5′-TTTG-3′, 5′-TTTC-3′, 5′-GTTA-3′, 5′-GTTT-3′, 5′-GTTG-3′, 5′-GTTC-3′, 5′-CTTA-3′, 5′-CTTT-3′, 5′-CTTG-3′, or 5′-CTTC-3′ sequence. In some embodiments, the deletion starts within about 5 to about 10 nucleotides (e.g., about 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 nucleotides) downstream of a T/C-rich sequence.

In some embodiments, the deletion starts within about 10 to about 15 nucleotides (e.g., about 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 nucleotides) of the 5′-NTTN-3′ sequence. In some embodiments, the deletion starts within about 10 to about 15 nucleotides (e.g., about 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 nucleotides) of a 5′-ATTA-3′, 5′-ATTT-3′, 5′-ATTG-3′, 5′-ATTC-3′, 5′-TTTA-3′, 5′-TTTT-3′, 5′-TTTG-3′, 5′-TTTC-3′, 5′-GTTA-3′, 5′-GTTT-3′, 5′-GTTG-3′, 5′-GTTC-3′, 5′-CTTA-3′, 5′-CTTT-3′, 5′-CTTG-3′, or 5′-CTTC-3′ sequence. In some embodiments, the deletion starts within about 10 to about 15 nucleotides (e.g., about 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 nucleotides) of a T/C-rich sequence.

In some embodiments, the deletion starts within about 10 to about 15 nucleotides (e.g., about 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 nucleotides) downstream of the 5′-NTTN-3′ sequence. In some embodiments, the deletion starts within about 10 to about 15 nucleotides (e.g., about 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 nucleotides) downstream of a 5′-ATTA-3′, 5′-ATTT-3′, 5′-ATTG-3′, 5′-ATTC-3′, 5′-TTTA-3′, 5′-TTTT-3′, 5′-TTTG-3′, 5′-TTTC-3′, 5′-GTTA-3′, 5′-GTTT-3′, 5′-GTTG-3′, 5′-GTTC-3′, 5′-CTTA-3′, 5′-CTTT-3′, 5′-CTTG-3′, or 5′-CTTC-3′ sequence. In some embodiments, the deletion starts within about 10 to about 15 nucleotides (e.g., about 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 nucleotides) downstream of a T/C-rich sequence.

In some embodiments, the deletion ends within about 20 to about 30 nucleotides (e.g., about 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, or 33 nucleotides) of the 5′-NTTN-3′ sequence. In some embodiments, the deletion ends within about 20 to about 30 nucleotides (e.g., about 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, or 33 nucleotides) of a 5′-ATTA-3′, 5′-ATTT-3′, 5′-ATTG-3′, 5′-ATTC-3′, 5′-TTTA-3′, 5′-TTTT-3′, 5′-TTTG-3′, 5′-TTTC-3′, 5′-GTTA-3′, 5′-GTTT-3′, 5′-GTTG-3′, 5′-GTTC-3′, 5′-CTTA-3′, 5′-CTTT-3′, 5′-CTTG-3′, or 5′-CTTC-3′ sequence. In some embodiments, the deletion ends within about 20 to about 30 nucleotides (e.g., about 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, or 33 nucleotides) of a T/C-rich sequence.

In some embodiments, the deletion ends within about 20 to about 30 nucleotides (e.g., about 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, or 33 nucleotides) downstream of the 5′-NTTN-3′ sequence. In some embodiments, the deletion ends within about 20 to about 30 nucleotides (e.g., about 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, or 33 nucleotides) downstream of a 5′-ATTA-3′, 5′-ATTT-3′, 5′-ATTG-3′, 5′-ATTC-3′, 5′-TTTA-3′, 5′-TTTT-3′, 5′-TTTG-3′, 5′-TTTC-3′, 5′-GTTA-3′, 5′-GTTT-3′, 5′-GTTG-3′, 5′-GTTC-3′, 5′-CTTA-3′, 5′-CTTT-3′, 5′-CTTG-3′, or 5′-CTTC-3′ sequence. In some embodiments, the deletion ends within about 20 to about 30 nucleotides (e.g., about 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, or 33 nucleotides) downstream of a T/C-rich sequence.

In some embodiments, the deletion ends within about 20 to about 25 nucleotides (e.g., about 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, or 28 nucleotides) of the 5′-NTTN-3′ sequence. In some embodiments, the deletion ends within about 20 to about 25 nucleotides (e.g., about 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, or 28 nucleotides) of a 5′-ATTA-3′, 5′-ATTT-3′, 5′-ATTG-3′, 5′-ATTC-3′, 5′-TTTA-3′, 5′-TTTT-3′, 5′-TTTG-3′, 5′-TTTC-3′, 5′-GTTA-3′, 5′-GTTT-3′, 5′-GTTG-3′, 5′-GTTC-3′, 5′-CTTA-3′, 5′-CTTT-3′, 5′-CTTG-3′, or 5′-CTTC-3′ sequence. In some embodiments, the deletion ends within about 20 to about 25 nucleotides (e.g., about 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, or 28 nucleotides) of a T/C-rich sequence.

In some embodiments, the deletion ends within about 20 to about 25 nucleotides (e.g., about 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, or 28 nucleotides) downstream of the 5′-NTTN-3′ sequence. In some embodiments, the deletion ends within about 20 to about 25 nucleotides (e.g., about 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, or 28 nucleotides) downstream of a 5′-ATTA-3′, 5′-ATTT-3′, 5′-ATTG-3′, 5′-ATTC-3′, 5′-TTTA-3′, 5′-TTTT-3′, 5′-TTTG-3′, 5′-TTTC-3′, 5′-GTTA-3′, 5′-GTTT-3′, 5′-GTTG-3′, 5′-GTTC-3′, 5′-CTTA-3′, 5′-CTTT-3′, 5′-CTTG-3′, or 5′-CTTC-3′ sequence. In some embodiments, the deletion ends within about 20 to about 25 nucleotides (e.g., about 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, or 28 nucleotides) downstream of a T/C-rich sequence.

In some embodiments, the deletion ends within about 25 to about 30 nucleotides (e.g., about 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, or 33 nucleotides) of the 5′-NTTN-3′ sequence. In some embodiments, the deletion ends within about 25 to about 30 nucleotides (e.g., about 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, or 33 nucleotides) of a 5′-ATTA-3′, 5′-ATTT-3′, 5′-ATTG-3′, 5′-ATTC-3′, 5′-TTTA-3′, 5′-TTTT-3′, 5′-TTTG-3′, 5′-TTTC-3′, 5′-GTTA-3′, 5′-GTTT-3′, 5′-GTTG-3′, 5′-GTTC-3′, 5′-CTTA-3′, 5′-CTTT-3′, 5′-CTTG-3′, or 5′-CTTC-3′ sequence. In some embodiments, the deletion ends within about 25 to about 30 nucleotides (e.g., about 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, or 33 nucleotides) of a T/C-rich sequence.

In some embodiments, the deletion ends within about 25 to about 30 nucleotides (e.g., about 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, or 33 nucleotides) downstream of the 5′-NTTN-3′ sequence. In some embodiments, the deletion ends within about 25 to about 30 nucleotides (e.g., about 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, or 33 nucleotides) downstream of a 5′-ATTA-3′, 5′-ATTT-3′, 5′-ATTG-3′, 5′-ATTC-3′, 5′-TTTA-3′, 5′-TTTT-3′, 5′-TTTG-3′, 5′-TTTC-3′, 5′-GTTA-3′, 5′-GTTT-3′, 5′-GTTG-3′, 5′-GTTC-3′, 5′-CTTA-3′, 5′-CTTT-3′, 5′-CTTG-3′, or 5′-CTTC-3′ sequence. In some embodiments, the deletion ends within about 25 to about 30 nucleotides (e.g., about 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, or 33 nucleotides) downstream of a T/C-rich sequence.

In some embodiments, the deletion starts within about 5 to about 15 nucleotides (e.g., about 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 nucleotides) and ends within about 20 to about 30 nucleotides (e.g., about 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, or 33 nucleotides) of the 5′-NTTN-3′ sequence. In some embodiments, the deletion starts within about 5 to about 15 nucleotides (e.g., about 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 nucleotides) and ends within about 20 to about 30 nucleotides (e.g., about 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, or 33 nucleotides) of a 5′-ATTA-3′, 5′-ATTT-3′, 5′-ATTG-3′, 5′-ATTC-3′, 5′-TTTA-3′, 5′-TTTT-3′, 5′-TTTG-3′, 5′-TTTC-3′, 5′-GTTA-3′, 5′-GTTT-3′, 5′-GTTG-3′, 5′-GTTC-3′, 5′-CTTA-3′, 5′-CTTT-3′, 5′-CTTG-3′, or 5′-CTTC-3′ sequence. In some embodiments, the deletion starts within about 5 to about 15 nucleotides (e.g., about 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 nucleotides) and ends within about 20 to about 30 nucleotides (e.g., about 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, or 33 nucleotides) of a T/C-rich sequence.

In some embodiments, the deletion starts within about 5 to about 15 nucleotides (e.g., about 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 nucleotides) downstream of the 5′-NTTN-3′ sequence and ends within about 20 to about 30 nucleotides (e.g., about 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, or 33 nucleotides) downstream of the 5′-NTTN-3′ sequence. In some embodiments, the deletion starts within about 5 to about 15 nucleotides (e.g., about 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 nucleotides) downstream of a 5′-ATTA-3′, 5′-ATTT-3′, 5′-ATTG-3′, 5′-ATTC-3′, 5′-TTTA-3′, 5′-TTTT-3′, 5′-TTTG-3′, 5′-TTTC-3′, 5′-GTTA-3′, 5′-GTTT-3′, 5′-GTTG-3′, 5′-GTTC-3′, 5′-CTTA-3′, 5′-CTTT-3′, 5′-CTTG-3′, or 5′-CTTC-3′ sequence and ends within about 20 to about 30 nucleotides (e.g., about 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, or 33 nucleotides) downstream of the 5′-ATTA-3′, 5′-ATTT-3′, 5′-ATTG-3′, 5′-ATTC-3′, 5′-TTTA-3′, 5′-TTTT-3′, 5′-TTTG-3′, 5′-TTTC-3′, 5′-GTTA-3′, 5′-GTTT-3′, 5′-GTTG-3′, 5′-GTTC-3′, 5′-CTTA-3′, 5′-CTTT-3′, 5′-CTTG-3′, or 5′-CTTC-3′ sequence. In some embodiments, the deletion starts within about 5 to about 15 nucleotides (e.g., about 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 nucleotides) downstream of a T/C-rich sequence and ends within about 20 to about 30 nucleotides (e.g., about 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, or 33 nucleotides) downstream of the T/C-rich sequence.

In some embodiments, the deletion starts within about 5 to about 15 nucleotides (e.g., about 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 nucleotides) and ends within about 20 to about 25 nucleotides (e.g., about 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, or 28 nucleotides) of the 5′-NTTN-3′ sequence. In some embodiments, the deletion starts within about 5 to about 15 nucleotides (e.g., about 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 nucleotides) and ends within about 20 to about 25 nucleotides (e.g., about 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, or 28 nucleotides) of a 5′-ATTA-3′, 5′-ATTT-3′, 5′-ATTG-3′, 5′-ATTC-3′, 5′-TTTA-3′, 5′-TTTT-3′, 5′-TTTG-3′, 5′-TTTC-3′, 5′-GTTA-3′, 5′-GTTT-3′, 5′-GTTG-3′, 5′-GTTC-3′, 5′-CTTA-3′, 5′-CTTT-3′, 5′-CTTG-3′, or 5′-CTTC-3′ sequence. In some embodiments, the deletion starts within about 5 to about 15 nucleotides (e.g., about 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 nucleotides) and ends within about 20 to about 25 nucleotides (e.g., about 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, or 28 nucleotides) of a T/C-rich sequence.

In some embodiments, the deletion starts within about 5 to about 15 nucleotides (e.g., about 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 nucleotides) downstream of the 5′-NTTN-3′ sequence and ends within about 20 to about 25 nucleotides (e.g., about 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, or 28 nucleotides) downstream of the 5′-NTTN-3′ sequence. In some embodiments, the deletion starts within about 5 to about 15 nucleotides (e.g., about 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 nucleotides) downstream of a 5′-ATTA-3′, 5′-ATTT-3′, 5′-ATTG-3′, 5′-ATTC-3′, 5′-TTTA-3′, 5′-TTTT-3′, 5′-TTTG-3′, 5′-TTTC-3′, 5′-GTTA-3′, 5′-GTTT-3′, 5′-GTTG-3′, 5′-GTTC-3′, 5′-CTTA-3′, 5′-CTTT-3′, 5′-CTTG-3′, or 5′-CTTC-3′ sequence and ends within about 20 to about 25 nucleotides (e.g., about 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, or 28 nucleotides) downstream of the 5′-ATTA-3′, 5′-ATTT-3′, 5′-ATTG-3′, 5′-ATTC-3′, 5′-TTTA-3′, 5′-TTTT-3′, 5′-TTTG-3′, 5′-TTTC-3′, 5′-GTTA-3′, 5′-GTTT-3′, 5′-GTTG-3′, 5′-GTTC-3′, 5′-CTTA-3′, 5′-CTTT-3′, 5′-CTTG-3′, or 5′-CTTC-3′ sequence. In some embodiments, the deletion starts within about 5 to about 15 nucleotides (e.g., about 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 nucleotides) downstream of a T/C-rich sequence and ends within about 20 to about 25 nucleotides (e.g., about 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, or 28 nucleotides) downstream of the T/C-rich sequence.

In some embodiments, the deletion starts within about 5 to about 15 nucleotides (e.g., about 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 nucleotides) and ends within about 25 to about 30 nucleotides (e.g., about 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, or 33 nucleotides) of the 5′-NTTN-3′ sequence. In some embodiments, the deletion starts within about 5 to about 15 nucleotides (e.g., about 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 nucleotides) and ends within about 25 to about 30 nucleotides (e.g., about 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, or 33 nucleotides) of a 5′-ATTA-3′, 5′-ATTT-3′, 5′-ATTG-3′, 5′-ATTC-3′, 5′-TTTA-3′, 5′-TTTT-3′, 5′-TTTG-3′, 5′-TTTC-3′, 5′-GTTA-3′, 5′-GTTT-3′, 5′-GTTG-3′, 5′-GTTC-3′, 5′-CTTA-3′, 5′-CTTT-3′, 5′-CTTG-3′, or 5′-CTTC-3′ sequence. In some embodiments, the deletion starts within about 5 to about 15 nucleotides (e.g., about 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 nucleotides) and ends within about 25 to about 30 nucleotides (e.g., about 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, or 33 nucleotides) of a T/C-rich sequence.

In some embodiments, the deletion starts within about 5 to about 15 nucleotides (e.g., about 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 nucleotides) downstream of the 5′-NTTN-3′ sequence and ends within about 25 to about 30 nucleotides (e.g., about 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, or 33 nucleotides) downstream of the 5′-NTTN-3′ sequence. In some embodiments, the deletion starts within about 5 to about 15 nucleotides (e.g., about 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 nucleotides) downstream of a 5′-ATTA-3′, 5′-ATTT-3′, 5′-ATTG-3′, 5′-ATTC-3′, 5′-TTTA-3′, 5′-TTTT-3′, 5′-TTTG-3′, 5′-TTTC-3′, 5′-GTTA-3′, 5′-GTTT-3′, 5′-GTTG-3′, 5′-GTTC-3′, 5′-CTTA-3′, 5′-CTTT-3′, 5′-CTTG-3′, or 5′-CTTC-3′ sequence and ends within about 25 to about 30 nucleotides (e.g., about 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, or 33 nucleotides) downstream of the 5′-ATTA-3′, 5′-ATTT-3′, 5′-ATTG-3′, 5′-ATTC-3′, 5′-TTTA-3′, 5′-TTTT-3′, 5′-TTTG-3′, 5′-TTTC-3′, 5′-GTTA-3′, 5′-GTTT-3′, 5′-GTTG-3′, 5′-GTTC-3′, 5′-CTTA-3′, 5′-CTTT-3′, 5′-CTTG-3′, or 5′-CTTC-3′ sequence. In some embodiments, the deletion starts within about 5 to about 15 nucleotides (e.g., about 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 nucleotides) downstream of a T/C-rich sequence and ends within about 25 to about 30 nucleotides (e.g., about 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, or 33 nucleotides) downstream of the T/C-rich sequence.

In some embodiments, the deletion starts within about 5 to about 10 nucleotides (e.g., about 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 nucleotides) and ends within about 20 to about 30 nucleotides (e.g., about 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, or 33 nucleotides) of the 5′-NTTN-3′ sequence. In some embodiments, the deletion starts within about 5 to about 10 nucleotides (e.g., about 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 nucleotides) and ends within about 20 to about 30 nucleotides (e.g., about 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, or 33 nucleotides) of a 5′-ATTA-3′, 5′-ATTT-3′, 5′-ATTG-3′, 5′-ATTC-3′, 5′-TTTA-3′, 5′-TTTT-3′, 5′-TTTG-3′, 5′-TTTC-3′, 5′-GTTA-3′, 5′-GTTT-3′, 5′-GTTG-3′, 5′-GTTC-3′, 5′-CTTA-3′, 5′-CTTT-3′, 5′-CTTG-3′, or 5′-CTTC-3′ sequence. In some embodiments, the deletion starts within about 5 to about 10 nucleotides (e.g., about 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 nucleotides) and ends within about 20 to about 30 nucleotides (e.g., about 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, or 33 nucleotides) of a T/C-rich sequence.

In some embodiments, the deletion starts within about 5 to about 10 nucleotides (e.g., about 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 nucleotides) downstream of the 5′-NTTN-3′ sequence and ends within about 20 to about 30 nucleotides (e.g., about 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, or 33 nucleotides) downstream of the 5′-NTTN-3′ sequence. In some embodiments, the deletion starts within about 5 to about 10 nucleotides (e.g., about 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 nucleotides) downstream of a 5′-ATTA-3′, 5′-ATTT-3′, 5′-ATTG-3′, 5′-ATTC-3′, 5′-TTTA-3′, 5′-TTTT-3′, 5′-TTTG-3′, 5′-TTTC-3′, 5′-GTTA-3′, 5′-GTTT-3′, 5′-GTTG-3′, 5′-GTTC-3′, 5′-CTTA-3′, 5′-CTTT-3′, 5′-CTTG-3′, or 5′-CTTC-3′ sequence and ends within about 20 to about 30 nucleotides (e.g., about 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, or 33 nucleotides) downstream of the 5′-ATTA-3′, 5′-ATTT-3′, 5′-ATTG-3′, 5′-ATTC-3′, 5′-TTTA-3′, 5′-TTTT-3′, 5′-TTTG-3′, 5′-TTTC-3′, 5′-GTTA-3′, 5′-GTTT-3′, 5′-GTTG-3′, 5′-GTTC-3′, 5′-CTTA-3′, 5′-CTTT-3′, 5′-CTTG-3′, or 5′-CTTC-3′ sequence. In some embodiments, the deletion starts within about 5 to about 10 nucleotides (e.g., about 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 nucleotides) downstream of a T/C-rich sequence and ends within about 20 to about 30 nucleotides (e.g., about 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, or 33 nucleotides) downstream of the T/C-rich sequence.

In some embodiments, the deletion starts within about 5 to about 10 nucleotides (e.g., about 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 nucleotides) and ends within about 20 to about 25 nucleotides (e.g., about 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, or 28 nucleotides) of the 5′-NTTN-3′ sequence. In some embodiments, the deletion starts within about 5 to about 10 nucleotides (e.g., about 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 nucleotides) and ends within about 20 to about 25 nucleotides (e.g., about 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, or 28 nucleotides) of a 5′-ATTA-3′, 5′-ATTT-3′, 5′-ATTG-3′, 5′-ATTC-3′, 5′-TTTA-3′, 5′-TTTT-3′, 5′-TTTG-3′, 5′-TTTC-3′, 5′-GTTA-3′, 5′-GTTT-3′, 5′-GTTG-3′, 5′-GTTC-3′, 5′-CTTA-3′, 5′-CTTT-3′, 5′-CTTG-3′, or 5′-CTTC-3′ sequence. In some embodiments, the deletion starts within about 5 to about 10 nucleotides and ends within about 20 to about 25 nucleotides (e.g., about 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, or 28 nucleotides) (e.g., about 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 nucleotides) of a T/C-rich sequence.

In some embodiments, the deletion starts within about 5 to about 10 nucleotides (e.g., about 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 nucleotides) downstream of the 5′-NTTN-3′ sequence and ends within about 20 to about 25 nucleotides (e.g., about 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, or 28 nucleotides) downstream of the 5′-NTTN-3′ sequence. In some embodiments, the deletion starts within about 5 to about 10 nucleotides (e.g., about 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 nucleotides) downstream of a 5′-ATTA-3′, 5′-ATTT-3′, 5′-ATTG-3′, 5′-ATTC-3′, 5′-TTTA-3′, 5′-TTTT-3′, 5′-TTTG-3′, 5′-TTTC-3′, 5′-GTTA-3′, 5′-GTTT-3′, 5′-GTTG-3′, 5′-GTTC-3′, 5′-CTTA-3′, 5′-CTTT-3′, 5′-CTTG-3′, or 5′-CTTC-3′ sequence and ends within about 20 to about 25 nucleotides (e.g., about 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, or 28 nucleotides) downstream of the 5′-ATTA-3′, 5′-ATTT-3′, 5′-ATTG-3′, 5′-ATTC-3′, 5′-TTTA-3′, 5′-TTTT-3′, 5′-TTTG-3′, 5′-TTTC-3′, 5′-GTTA-3′, 5′-GTTT-3′, 5′-GTTG-3′, 5′-GTTC-3′, 5′-CTTA-3′, 5′-CTTT-3′, 5′-CTTG-3′, or 5′-CTTC-3′ sequence. In some embodiments, the deletion starts within about 5 to about 10 nucleotides (e.g., about 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 nucleotides) downstream of a T/C-rich sequence and ends within about 20 to about 25 nucleotides (e.g., about 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, or 28 nucleotides) downstream of the T/C-rich sequence.

In some embodiments, the deletion starts within about 5 to about 10 nucleotides (e.g., about 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 nucleotides) and ends within about 25 to about 30 nucleotides (e.g., about 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, or 33 nucleotides) of the 5′-NTTN-3′ sequence. In some embodiments, the deletion starts within about 5 to about 10 nucleotides (e.g., about 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 nucleotides) and ends within about 25 to about 30 nucleotides (e.g., about 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, or 33 nucleotides) of a T/C-rich sequence.

In some embodiments, the deletion starts within about 5 to about 10 nucleotides (e.g., about 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 nucleotides) downstream of the 5′-NTTN-3′ sequence and ends within about 25 to about 30 nucleotides (e.g., about 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, or 33 nucleotides) downstream of the 5′-NTTN-3′ sequence. In some embodiments, the deletion starts within about 5 to about 10 nucleotides (e.g., about 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 nucleotides) downstream of a 5′-ATTA-3′, 5′-ATTT-3′, 5′-ATTG-3′, 5′-ATTC-3′, 5′-TTTA-3′, 5′-TTTT-3′, 5′-TTTG-3′, 5′-TTTC-3′, 5′-GTTA-3′, 5′-GTTT-3′, 5′-GTTG-3′, 5′-GTTC-3′, 5′-CTTA-3′, 5′-CTTT-3′, 5′-CTTG-3′, or 5′-CTTC-3′ sequence and ends within about 25 to about 30 nucleotides (e.g., about 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, or 33 nucleotides) downstream of the 5′-ATTA-3′, 5′-ATTT-3′, 5′-ATTG-3′, 5′-ATTC-3′, 5′-TTTA-3′, 5′-TTTT-3′, 5′-TTTG-3′, 5′-TTTC-3′, 5′-GTTA-3′, 5′-GTTT-3′, 5′-GTTG-3′, 5′-GTTC-3′, 5′-CTTA-3′, 5′-CTTT-3′, 5′-CTTG-3′, or 5′-CTTC-3′ sequence. In some embodiments, the deletion starts within about 5 to about 10 nucleotides (e.g., about 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 nucleotides) downstream of a T/C-rich sequence and ends within about 25 to about 30 nucleotides (e.g., about 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, or 33 nucleotides) downstream of the T/C-rich sequence.

In some embodiments, the deletion starts within about 10 to about 15 nucleotides (e.g., about 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 nucleotides) and ends within about 20 to about 30 nucleotides (e.g., about 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, or 33 nucleotides) of the 5′-NTTN-3′ sequence. In some embodiments, the deletion starts within about 10 to about 15 nucleotides (e.g., about 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 nucleotides) and ends within about 20 to about 30 nucleotides (e.g., about 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, or 33 nucleotides) of a 5′-ATTA-3′, 5′-ATTT-3′, 5′-ATTG-3′, 5′-ATTC-3′, 5′-TTTA-3′, 5′-TTTT-3′, 5′-TTTG-3′, 5′-TTTC-3′, 5′-GTTA-3′, 5′-GTTT-3′, 5′-GTTG-3′, 5′-GTTC-3′, 5′-CTTA-3′, 5′-CTTT-3′, 5′-CTTG-3′, or 5′-CTTC-3′ sequence. In some embodiments, the deletion starts within about 10 to about 15 nucleotides (e.g., about 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 nucleotides) and ends within about 20 to about 30 nucleotides (e.g., about 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, or 33 nucleotides) of a T/C-rich sequence.

In some embodiments, the deletion starts within about 10 to about 15 nucleotides (e.g., about 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 nucleotides) downstream of the 5′-NTTN-3′ sequence and ends within about 20 to about 30 nucleotides (e.g., about 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, or 33 nucleotides) downstream of the 5′-NTTN-3′ sequence. In some embodiments, the deletion starts within about 10 to about 15 nucleotides (e.g., about 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 nucleotides) downstream of a 5′-ATTA-3′, 5′-ATTT-3′, 5′-ATTG-3′, 5′-ATTC-3′, 5′-TTTA-3′, 5′-TTTT-3′, 5′-TTTG-3′, 5′-TTTC-3′, 5′-GTTA-3′, 5′-GTTT-3′, 5′-GTTG-3′, 5′-GTTC-3′, 5′-CTTA-3′, 5′-CTTT-3′, 5′-CTTG-3′, or 5′-CTTC-3′ sequence and ends within about 20 to about 30 nucleotides (e.g., about 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, or 33 nucleotides) downstream of the 5′-ATTA-3′, 5′-ATTT-3′, 5′-ATTG-3′, 5′-ATTC-3′, 5′-TTTA-3′, 5′-TTTT-3′, 5′-TTTG-3′, 5′-TTTC-3′, 5′-GTTA-3′, 5′-GTTT-3′, 5′-GTTG-3′, 5′-GTTC-3′, 5′-CTTA-3′, 5′-CTTT-3′, 5′-CTTG-3′, or 5′-CTTC-3′ sequence. In some embodiments, the deletion starts within about 10 to about 15 nucleotides (e.g., about 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 nucleotides) downstream of a T/C-rich sequence and ends within about 20 to about 30 nucleotides (e.g., about 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, or 33 nucleotides) downstream of the T/C-rich sequence.

In some embodiments, the deletion starts within about 10 to about 15 nucleotides (e.g., about 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 nucleotides) and ends within about 20 to about 25 nucleotides (e.g., about 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, or 28 nucleotides) of the 5′-NTTN-3′ sequence. In some embodiments, the deletion starts within about 10 to about 15 nucleotides (e.g., about 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 nucleotides) and ends within about 20 to about 25 nucleotides (e.g., about 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, or 28 nucleotides) of a 5′-ATTA-3′, 5′-ATTT-3′, 5′-ATTG-3′, 5′-ATTC-3′, 5′-TTTA-3′, 5′-TTTT-3′, 5′-TTTG-3′, 5′-TTTC-3′, 5′-GTTA-3′, 5′-GTTT-3′, 5′-GTTG-3′, 5′-GTTC-3′, 5′-CTTA-3′, 5′-CTTT-3′, 5′-CTTG-3′, or 5′-CTTC-3′ sequence. In some embodiments, the deletion starts within about 10 to about 15 nucleotides (e.g., about 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 nucleotides) and ends within about 20 to about 25 nucleotides (e.g., about 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, or 28 nucleotides) of a T/C-rich sequence.

In some embodiments, the deletion starts within about 10 to about 15 nucleotides (e.g., about 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 nucleotides) downstream of the 5′-NTTN-3′ sequence and ends within about 20 to about 25 nucleotides (e.g., about 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, or 28 nucleotides) downstream of the 5′-NTTN-3′ sequence. In some embodiments, the deletion starts within about 10 to about 15 nucleotides (e.g., about 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 nucleotides) downstream of a 5′-ATTA-3′, 5′-ATTT-3′, 5′-ATTG-3′, 5′-ATTC-3′, 5′-TTTA-3′, 5′-TTTT-3′, 5′-TTTG-3′, 5′-TTTC-3′, 5′-GTTA-3′, 5′-GTTT-3′, 5′-GTTG-3′, 5′-GTTC-3′, 5′-CTTA-3′, 5′-CTTT-3′, 5′-CTTG-3′, or 5′-CTTC-3′ sequence and ends within about 20 to about 25 nucleotides (e.g., about 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, or 28 nucleotides) downstream of the 5′-ATTA-3′, 5′-ATTT-3′, 5′-ATTG-3′, 5′-ATTC-3′, 5′-TTTA-3′, 5′-TTTT-3′, 5′-TTTG-3′, 5′-TTTC-3′, 5′-GTTA-3′, 5′-GTTT-3′, 5′-GTTG-3′, 5′-GTTC-3′, 5′-CTTA-3′, 5′-CTTT-3′, 5′-CTTG-3′, or 5′-CTTC-3′ sequence. In some embodiments, the deletion starts within about 10 to about 15 nucleotides (e.g., about 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 nucleotides) downstream of a T/C-rich sequence and ends within about 20 to about 25 nucleotides (e.g., about 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, or 28 nucleotides) downstream of the T/C-rich sequence.

In some embodiments, the deletion starts within about 10 to about 15 nucleotides (e.g., about 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 nucleotides) and ends within about 25 to about 30 nucleotides (e.g., about 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, or 33 nucleotides) of the 5′-NTTN-3′ sequence. In some embodiments, the deletion starts within about 10 to about 15 nucleotides (e.g., about 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 nucleotides) and ends within about 25 to about 30 nucleotides (e.g., about 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, or 33 nucleotides) of a 5′-ATTA-3′, 5′-ATTT-3′, 5′-ATTG-3′, 5′-ATTC-3′, 5′-TTTA-3′, 5′-TTTT-3′, 5′-TTTG-3′, 5′-TTTC-3′, 5′-GTTA-3′, 5′-GTTT-3′, 5′-GTTG-3′, 5′-GTTC-3′, 5′-CTTA-3′, 5′-CTTT-3′, 5′-CTTG-3′, or 5′-CTTC-3′ sequence. In some embodiments, the deletion starts within about 10 to about 15 nucleotides (e.g., about 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 nucleotides) and ends within about 25 to about 30 nucleotides (e.g., about 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, or 33 nucleotides) of a T/C-rich sequence.

In some embodiments, the deletion starts within about 10 to about 15 nucleotides (e.g., about 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 nucleotides) downstream of the 5′-NTTN-3′ sequence and ends within about 25 to about 30 nucleotides (e.g., about 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, or 33 nucleotides) downstream of the 5′-NTTN-3′ sequence. In some embodiments, the deletion starts within about 10 to about 15 nucleotides (e.g., about 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 nucleotides) downstream of a 5′-ATTA-3′, 5′-ATTT-3′, 5′-ATTG-3′, 5′-ATTC-3′, 5′-TTTA-3′, 5′-TTTT-3′, 5′-TTTG-3′, 5′-TTTC-3′, 5′-GTTA-3′, 5′-GTTT-3′, 5′-GTTG-3′, 5′-GTTC-3′, 5′-CTTA-3′, 5′-CTTT-3′, 5′-CTTG-3′, or 5′-CTTC-3′ sequence and ends within about 25 to about 30 nucleotides (e.g., about 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, or 33 nucleotides) downstream of the 5′-ATTA-3′, 5′-ATTT-3′, 5′-ATTG-3′, 5′-ATTC-3′, 5′-TTTA-3′, 5′-TTTT-3′, 5′-TTTG-3′, 5′-TTTC-3′, 5′-GTTA-3′, 5′-GTTT-3′, 5′-GTTG-3′, 5′-GTTC-3′, 5′-CTTA-3′, 5′-CTTT-3′, 5′-CTTG-3′, or 5′-CTTC-3′ sequence. In some embodiments, the deletion starts within about 10 to about 15 nucleotides (e.g., about 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 nucleotides) downstream of a T/C-rich sequence and ends within about 25 to about 30 nucleotides (e.g., about 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, or 33 nucleotides) downstream of the T/C-rich sequence.

In some embodiments, the deletion is up to about 50 nucleotides in length (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50 nucleotides). In some embodiments, the deletion is up to about 40 nucleotides in length (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, or 45 nucleotides). In some embodiments, the deletion is between about 4 nucleotides and about 40 nucleotides in length (e.g., about 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, or 45 nucleotides). In some embodiments, the deletion is between about 4 nucleotides and about 25 nucleotides in length (e.g., about 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, or 28 nucleotides). In some embodiments, the deletion is between about 10 nucleotides and about 25 nucleotides in length (e.g., about 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, or 28 nucleotides). In some embodiments, the deletion is between about 10 nucleotides and about 15 nucleotides in length (e.g., about 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 nucleotides).

In some embodiments, the methods described herein are used to engineer a cell comprising a deletion as described herein in a BCL11A gene.

Compositions, vectors, nucleic acids, RNA guides and cells disclosed herein may be used in therapy. Compositions, vectors, nucleic acids, RNA guides and cells disclosed herein may be used in methods of treating a disease or condition in a subject. Any suitable delivery or administration method known in the art may be used to deliver compositions, vectors, nucleic acids, RNA guides and cells disclosed herein. Such methods may involve contacting a target sequence with a composition, vector, nucleic acid, or RNA guide disclosed herein. Such methods may involve a method of editing a BCL11A sequence as disclosed herein. In some embodiments, a cell engineered using an RNA guide disclosed herein is used for ex vivo gene therapy. In some embodiments, the compositions, vectors, nucleic acids, RNA guides and cells disclosed herein are used in the treatment of sickle cell anemia. In some embodiments, the compositions, vectors, nucleic acids, RNA guides and cells disclosed herein are used in the treatment of beta-thalassemia. In some embodiments, wherein one or more RNA guides targets the enhancer region of BCL11A (SEQ ID NO: 2640), the one or more RNA guides are used in the treatment of sickle cell anemia or beta-thalassemia.

Kits

The invention also provides kits or systems that can be used, for example, to carry out a method described herein. In some embodiments, the kits or systems include an RNA guide and a Cas12i polypeptide. In some embodiments, the kits or systems include a polynucleotide that encodes such a Cas12i polypeptide, and optionally the polynucleotide is comprised within a vector, e.g., as described herein. In some embodiments, the kits or systems include a polynucleotide that encodes an RNA guide disclosed herein. The Cas12i polypeptide and the RNA guide (e.g., as a ribonucleoprotein) can be packaged within the same or other vessel within a kit or system or can be packaged in separate vials or other vessels, the contents of which can be mixed prior to use. The kits or systems can additionally include, optionally, a buffer and/or instructions for use of the RNA guide and Cas12i polypeptide.

All references and publications cited herein are hereby incorporated by reference.

EXAMPLES

The following examples are provided to further illustrate some embodiments of the present invention but are not intended to limit the scope of the invention; it will be understood by their exemplary nature that other procedures, methodologies, or techniques known to those skilled in the art may alternatively be used.

Example 1—Editing of BCL11A in a Mammalian Cell

This example describes generation of modified CD34+ hematopoietic stem/progenitor cells (HSPC) with variant Cas12i2. For this study, human primary CD34+ HSPCs were transfected with BCL11A intronic erythroid enhancer-targeting RNPs comprising variant Cas12i2 of SEQ ID NO: 2642 and RNA guide. The modified CD34+ HSPCs were analyzed by FACS staining and indel assessment at the BCL11A intronic erythroid enhancer target.

Two frozen human bone marrow CD34+ cell vials per cell lot were thawed (Day 0), washed and assessed for cell number and viability by acridine orange/propidium iodide (AO/PI) staining using a cell counter. CD34+ cells were cultured in serum-free expansion media (from StemCell Technologies) with the appropriate supplement for approximately 48 hours.

RNP Complexation Reactions:

Variant Cas12i2 RNP complexes were prepared by mixing purified variant Cas12i2 of SEQ ID NO: 2642 (400 μM) with different RNA guides (1 mM in 250 mM NaCl) at a 1:1 Cas12i2 effector:RNA guide volume ratio (corresponding to 2.5:1 RNA guide:Cas12i2 effector molar ratio). SpCas9 RNP complexes were prepared by mixing purified SpCas9 (62 μM) with single guide RNA (sgRNA) (1 mM in water) at a 6.45:1 SpCas9 effector: sgRNA volume ratio (corresponding to 2.5:1 sgRNA: SpCas9 effector molar ratio). SpCas9 protein was purchased from Aldevron. Sequences of RNA guides and sgRNA are shown in Table 6.

TABLE 6

Sequences of BCL11A intronic erythroid enhancer-targeting RNA guides (for variant

Cas12i2) and sgRNA (for SpCas9) used for RNP complexes

DNA

Guide Name
Gene
Effector
PAM
Strand
RNA guide

Cas12i2_BCL11A_
BCL11A
Cas12i2
CTTT
Antise
AGAAAUCCGUCUUUCAUUGACGGG

enh_T1
enhancer

nse
AAGCUAGUCUAGUGCAAGC (SEQ ID

NO: 2677)

Cas12i2_BCL11A_
BCL11A
Cas12i2
CTTC
Sense
AGAAAUCCGUCUUUCAUUGACGGC

enh_T4
enhancer

UGGAGCCUGUGAUAAAAGC (SEQ ID

NO: 2678)

Cas12i2_BCL11A_
BCL11A
Cas1212
CTTC
Sense
AGAAAUCCGUCUUUCAUUGACGGU

enh_T5
enhancer

ACCCCACCCACGCCCCCAC (SEQ ID

NO: 2679)

SpCas9_BCL11A_
BCL11A
SpCas9
AGG
Antise
mC*mU*mA*ACAGUUGCUUUUAUCA

enh_T1
enhancer

nse
CGUUUUAGAGCUAGAAAUAGCAAG

UUAAAAUAAGGCUAGUCCGUUAUC

AACUUGAAAAAGUGGCACCGAGUC

GGUGCmU*mU*mU*U (SEQ ID NO:

2680)

*-phosphorothioated

m-2′ O-methyl

For effector only controls, variant Cas12i2 or SpCas9 were mixed with protein storage buffer (25 mM Tris, pH 7.5, 250 mM NaCl, 1 mM TCEP, 50% glycerol) at the same volume ratio as the RNA guide or sgRNA, respectively. Complexations were incubated at 37 degrees Celsius for 30-60 minutes. Following incubation, RNPs were diluted to 18.75 μM, 50 μM, 100 μM, or 160 μM effector concentration for variant Cas12i2 and 18.75 μM or 50 μM for SpCas9. For multiplexing, separate RNPs were mixed together prior to electroporation.

On Day 2, approximately 1e5 cells per electroporation reaction, plus 20% extra, were harvested and counted. Cells were washed once with PBS and resuspended in buffer+supplement (from Lonza #VXP-3032)+1 mM transfection enhancer oligo (to bring concentration to 4.28 μM in P3 buffer). Concentration of resuspended cells was approximately 5,555 cells/μL. 18 μL of resuspended cells (˜1e5 cells) were mixed with 2 μL of individual or multiplexed RNP complexes to bring final concentration of variant Cas12i2 RNPs to 1.875 PM, 5 PM, 10 μM or 16 PM. Final concentration of SpCas9 RNPs was 1.875 μM or 5 μM. The following controls were set up: unelectroporated cells only, cells in protein storage buffer only. The plate was electroporated using an electroporation device, excluding the unelectroporated conditions. Each electroporation reaction was transferred into 24-well culture plate well containing pre-warmed serum-free media and the appropriate supplement. Cultures were incubated at 37 degrees Celsius, 5% CO₂for 3 days.

A portion of cell samples (approximately 20 μL) from each test condition was collected at 24, 48, and 72 h post electroporation. Viability was evaluated using AO/PI stain on a cell counter.

On Day 3, cell pellets were prepared from cells remaining after viability testing. Approximately 5e4 cells from each sample were harvested and transferred to a microcentrifuge tube. Cells were pelleted at 1500 rpm for 5 min. Supernatants were removed and pellets were frozen at −80° C.

For genomic DNA extraction, pellets were thawed to room temperature and resuspended in appropriate volume of DNA extraction buffer (from Lucigen) to give final concentration of 1000 cells/μL. Samples were then cycled in PCR machine at 65° C. for 15 min, 68° C. for 15 min, 98° C. for 10 min. Samples were then frozen at −20° C.

Samples for Next Generation Sequencing (NGS) were prepared by rounds of PCR. The first round (PCR I) was used to amplify the genomic regions flanking the target site and add NGS adapters. The second round (PCR II) was used to add NGS indexes. Reactions were then pooled, purified by column purification, and quantified on a fluorometer (Qubit). Sequencing runs were done using a 300 or 150 cycle NGS instrument (NextSeq v2.5) mid or high output kit and run on an NGS instrument (NextSeq 550).

For NGS analysis, the indel mapping function used a sample's fastq file, the amplicon reference sequence, and the forward primer sequence. For each read, a kmer-scanning algorithm was used to calculate the edit operations (match, mismatch, insertion, deletion) between the read and the reference sequence. In order to remove small amounts of primer dimer present in some samples, the first 30 nucleotides of each read were required to match the reference and reads where over half of the mapping nucleotides are mismatches were filtered out as well. Up to 50,000 reads passing those filters were used for analysis, and reads were counted as an indel read if they contained an insertion or deletion. The indel % was calculated as the number of indel-containing reads divided by the number of reads analyzed (reads passing filters up to 50,000). The QC standard for the minimum number of reads passing filters was 10,000. Indels were further assessed for disruption of the GATAA motif sequence by searching for TTATC (reverse complement of GATAA sequence, on the forward strand) sequence in each indel.

FIG. 1 and FIG. 2 demonstrate the results of this example. As shown in FIG. 1, BCL11A intronic erythroid enhancer-targeting RNP complexes comprising variant Cas12i2 and RNA guide resulted in indel activity in primary CD34+ HSPCs. The data showed that at least 50% of variant Cas12i2-induced indels partially or fully disrupted the GATAA motif of BCL11A intronic erythroid enhancer region.

FIG. 2 illustrates that modified CD34+ HSPCs generated with variant Cas12i2 editing of BCL11A intronic erythroid enhance were viable at least 72 hours after treatment of primary CD34+ HSPCs with variant Cas12i2 RNP complexes.

This example demonstrated that Cas12i2 complexed with the tested RNA guides comprised robust indel activity. Variant Cas12i2 RNPs that targeted BCL11A intronic erythroid enhancer region-targeting were used to generate modified CD34+ HSPCs and resulted in at least about 50% partial or complete disruption of the GATAA motif in the modified cells. The results also show that more than one RNA guide (e.g., multiplexed RNA guides) can be used to introduce indels into BCL11A.

Nucleotide
atgagcagcg cgatcaaaag ctacaagagc gttctgcgtc cgaacgagcg taagaaccaa
60

sequence
ctgctgaaaa gcaccattca gtgcctggaa gacggtagcg cgttcttttt caagatgctg
120

encoding
caaggcctgt ttggtggcat caccccggag attgttcgtt tcagcaccga acaggagaaa
180

Cas12i2-
cagcaacagg atatcgcgct gtggtgcgcg gttaactggt tccgtccggt gagccaagac
240

SEQ ID NO:
agcctgaccc acaccattgc gagcgataac ctggtggaga agtttgagga atactatggt
300

2633
ggcaccgcga gcgacgcgat caaacagtac ttcagcgcga gcattggcga aagctactat
360

tggaacgact gccgtcaaca gtactatgat ctgtgccgtg agctgggtgt tgaggtgagc
420

gacctgaccc atgatctgga gatcctgtgc cgtgaaaagt gcctggcggt tgcgaccgag
480

agcaaccaga acaacagcat cattagcgtt ctgtttggca ccggcgaaaa agaggaccgt
540

agcgtgaaac tgcgtatcac caagaaaatt ctggaggcga tcagcaacct gaaagaaatc
600

ccgaagaacg ttgcgccgat tcaagagatc attctgaacg tggcgaaagc gaccaaggaa
660

accttccgtc aggtgtatgc gggtaacctg ggtgcgccga gcaccctgga gaaatttatc
720

gcgaaggacg gccaaaaaga gttcgatctg aagaaactgc agaccgacct gaagaaagtt
780

attcgtggta aaagcaagga gcgtgattgg tgctgccagg aagagctgcg tagctacgtg
840

gagcaaaaca ccatccagta tgacctgtgg gcgtggggcg aaatgttcaa caaagcgcac
900

accgcgctga aaatcaagag cacccgtaac tacaactttg cgaagcaacg tctggaacag
960

ttcaaagaga ttcagagcct gaacaacctg ctggttgtga agaagctgaa cgactttttc
1020

gatagcgaat ttttcagcgg cgaggaaacc tacaccatct gcgttcacca tctgggggc
1080

aaggacctga gcaaactgta taaggcgtgg gaggatgatc cggcggaccc ggaaaacgcg
1140

attgtggttc tgtgcgacga tctgaaaaac aactttaaga aagagccgat ccgtaacatt
1200

ctgcgttaca tcttcaccat tcgtcaagaa tgcagcgcgc aggacatcct ggcggcggcg
1260

aagtacaacc aacagctgga tcgttataaa agccaaaagg cgaacccgag cgttctgggt
1320

aaccagggct ttacctggac caacgcggtg atcctgccgg agaaggcgca gcgtaacgac
1380

cgtccgaaca gcctggatct gcgtatttgg ctgtacctga aactgcgtca cccggacggt
1440

cgttggaaga aacaccatat cccgttctac gatacccgtt tcttccaaga aatttatgcg
1500

gcgggcaaca gcccggttga cacctgccag tttcgtaccc cgcgtttcgg ttatcacctg
1560

ccgaaactga ccgatcagac cgcgatccgt gttaacaaga aacatgtgaa agcggcgaag
1620

accgaggcgc gtattcgtct ggcgatccaa cagggcaccc tgccggtgag caacctgaag
1680

atcaccgaaa ttagcgcgac catcaacagc aaaggtcaag tgcgtattcc ggttaagttt
1740

gacgtgggtc gtcaaaaagg caccctgcag atcggtgacc gtttctgcgg ctacgatcaa
1800

aaccagaccg cgagccacgc gtatagcctg tgggaagtgg ttaaagaggg tcaataccat
1860

aaagagctgg gctgctttgt tcgtttcatc agcagcggtg acatcgtgag cattaccgag
1920

aaccgtggca accaatttga tcagctgagc tatgaaggtc tggcgtaccc gcaatatgcg
1980

gactggcgta agaaagcgag caagttcgtg agcctgtggc agatcaccaa gaaaaacaag
2040

aaaaaggaaa tcgtgaccgt tgaagcgaaa gagaagtttg acgcgatctg caagtaccag
2100

ccgcgtctgt ataaattcaa caaggagtac gcgtatctgc tgcgtgatat tgttcgtggc
2160

aaaagcctgg tggaactgca acagattcgt caagagatct ttcgtttcat tgaacaggac
2220

tgcggtgtta cccgtctggg cagcctgagc ctgagcaccc tggaaaccgt gaaagcggtt
2280

aagggtatca tttacagcta ttttagcacc gcgctgaacg cgagcaagaa caacccgatc
2340

agcgacgaac agcgtaaaga gtttgatccg gaactgttcg cgctgctgga aaagctggag
2400

ctgattcgta cccgtaaaaa gaaacaaaaa gtggaacgta tcgcgaacag cctgattcag
2460

acctgcctgg agaacaacat caagttcatt cgtggtgaag gcgacctgag caccaccaac
2520

aacgcgacca agaaaaaggc gaacagccgt agcatggatt ggttggcgcg tggtgttttt
2680

aacaaaatcc gtcaactggc gccgatgcac aacattaccc tgttcggttg cggcagcctg
2640

tacaccagcc accaggaccc gctggtgcat cgtaacccgg ataaagcgat gaagtgccgt
2700

tgggcggcga tcccggttaa ggacattggc gattgggtgc tgcgtaagct gagccaaaac
2760

ctgcgtgcga aaaacatcgg caccggcgag tactatcacc aaggtgttaa agagttcctg
2820

agccattatg aactgcagga cctggaggaa gagctgctga agtggcgtag cgatcgtaaa
2880

agcaacattc cgtgctgggt gctgcagaac cgtctggcgg agaagctggg caacaaagaa
2940

gcggtggttt acatcccggt tcgtggtggc cgtatttatt ttgcgaccca caaggtggcg
3000

accggtgcgg tgagcatcgt tttcgaccaa aaacaagtgt gggtttgcaa cgcggatcat
3060

gttgcggcgg cgaacatcgc gctgaccgtg aagggtattg gcgaacaaag cagcgacgaa
3120

gagaacccgg atggtagccg tatcaaactg cagctgacca gc
3162

Cas12i2
MSSAIKSYKSVLRPNERKNQLLKSTIQCLEDGSAFFFKMLQGLEGGITPEIVRESTEQEK

amino acid
QQQDIALWCAVNWFRPVSQDSLTHTIASDNLVEKFEEYYGGTASDAIKQYFSASIGESYY

sequence-
WNDCRQQYYDLCRELGVEVSDLTHDLEILCREKCLAVATESNQNNSIISVLFGTGEKEDR

SEQ ID NO:
SVKLRITKKILEAISNLKEIPKNVAPIQEIILNVAKATKETFRQVYAGNLGAPSTLEKFI

2634
AKDGQKEFDLKKLQTDLKKVIRGKSKERDWCCQEELRSYVEQNTIQYDLWAWGEMENKAH

TALKIKSTRNYNFAKQRLEQFKEIQSLNNLLVVKKLNDFFDSEFFSGEETYTICVHHLGG

KDLSKLYKAWEDDPADPENAIVVLCDDLKNNFKKEPIRNILRYIFTIRQECSAQDILAAA

KYNQQLDRYKSQKANPSVLGNQGFTWTNAVILPEKAQRNDRPNSLDLRIWLYLKLRHPDG

RWKKHHIPFYDTRFFQEIYAAGNSPVDTCQFRTPRFGYHLPKLTDQTAIRVNKKHVKAAK

TEARIRLAIQQGTLPVSNLKITEISATINSKGQVRIPVKFDVGRQKGTLQIGDRFCGYDQ

NQTASHAYSLWEVVKEGQYHKELGCFVRFISSGDIVSITENRGNQFDQLSYEGLAYPQYA

DWRKKASKFVSLWQITKKNKKKEIVTVEAKEKFDAICKYQPRLYKENKEYAYLLRDIVRG

KSLVELQQIRQEIFRFIEQDCGVTRLGSLSLSTLETVKAVKGIIYSYFSTALNASKNNPI

SDEQRKEFDPELFALLEKLELIRTRKKKQKVERIANSLIQTCLENNIKFIRGEGDLSTIN

NATKKKANSRSMDWLARGVFNKIRQLAPMHNITLFGCGSLYTSHQDPLVHRNPDKAMKCR

WAAIPVKDIGDWVLRKLSQNLRAKNIGTGEYYHQGVKEFLSHYELQDLEEELLKWRSDRK

SNIPCWVLQNRLAEKLGNKEAVVYIPVRGGRIYFATHKVATGAVSIVFDQKQVWVCNADH

VAAANIALTVKGIGEQSSDEENPDGSRIKLQLTS

BCL11A-
GTCTCTGTCCATCCAGACTCCTGACGTTCAAGTTCGCAGGGACGTCACGTCCGCACTTGAACTTG

SEQ ID NO:
CAGCTCAGGGGGGCTTTTGCCATTTTTTTCATCTCTCTCTCTCTCTCTCCCTCTATCTCTCTTCT

2635
CTCTCTCTCCCTCTTTTTTTTTTTTTTTTTTTTTTTTTTTTTGCTTAAAAAAAAGCCATGACGGC

TCTCCCACAATTCATCTTCCCTGCGCCATCTTTGTATTATTTCTAATTTATTTTGGATGTCAAAA

GGCACTGATGAAGATATTTTCTCTGGAGTCTCCTTCTTTCTAACCCGGCTCTCCCGATGTGAACC

GAGCCGTCGTCCGCCCGCCGCCGCCGCCGCCGCCGCCGCCGCCCGCCCCGCAGCCCACCATGTCT

CGCCGCAAGCAAGGCAAACCCCAGCACTTAAGCAAACGGGAATTCTCGCGTAAGTAACCCAATAA

TAGTAATAATAATTATTAATAATCACGAGAGCGCGCAGGACTAGAAGCAAAAGCGAGGGGGAGAG

AGGGGTGTGTGCATGCATTTTTAAATTTTTCACGAGAAAAACCTCCGAGAGTCGAGGTAAAAGAG

ATAAAGGGGGAAAAAACCCTCATCCCATCTGGAACCATTGCCGTGTATGCACTTTTGAGACAGCA

CGCACCTTTTAATTTTATTTAATTTTACAAAAATTTGACTCCTCCTCTTTCCTCCTTTCCGCCGC

TTTATTTCTCTTTTCGAAAAGGAATGCAATGATTCCACTCCCCCCCCGCCCCGCCAGTTTTGCAA

AATAATGAACAATGCTAAGGTTGCGAACAACTCACATGCAAACCTGGGGGTGGGAGCTGGTGGGG

AAAGGGAGGTTGCTTCCCACTCACCGTAAGAAAATGGGGGGGTAGGGAGGGAGTGAGTACAAGTC

TAAAAAACGATTCCCGGGGAGAAAAGAGGTGAGACTGGCTTTTGGACACCAGCGCGCTCACGGTC

AAGTGTGCAGCGGGAGGAAAGTAGTCATCCCCACAATAGTGAGAAAGTGGCACTGTGGAAAGGGG

CCCCCGGCGCTCCTGAGTCCGCGGAGTCGGGAGAGGGGCCGCGGCGACGGGGAGAGCCGTGGGAC

CGGGAAGGACGGGAGACGCGGCCGGCACTGCCGCCTTTTGTTCCGGCCAGAGGTGGGTGTTTGTC

CCGCTGCCTTTTGTGCCGGCTCCTCGCGCTTGCCCTCCCGCGCCGCCGCCGCCGCCGCCGCCGAA

GGGCAGGAGCTAGGGCCGGGGGAGGAGGCGGCCGGGGGCACGCGGGAGAGGGAGGGAGGGAGCCC

GGACTGCTGCCTCCTGGGTTGCCGCTGCCCTCCCCTCCCGACCGAACCTCAGAGGCAGCAAGGAG

AAGACTGGCACATAAATAAATAAATACATAAAAATAAAATAAATAAAACAAGGCAAGAGAATGTA

CAATTTCTTGCCCCCAAACCGAAGCCAAACGCTCTGCCAACCCTTTTCTGTGACGGCCTTCTCTT

TGACTCCCCCACCAGCCCCCCTGCAAAAATCTCACAATCTCTCATCTAGAAAAAAATTTACAATC

ACCCTCTTCCCCCAAACCCCTTCAGTTGCAAACTTAGGGCGCCGACGGCACGGAGAGGGAGAGAG

GAACTCCCTCCTCTTACTATTTTTTGGAAGATTTTCAAAAAAAGTGGAAGTGGATTTTGATTGGG

AAAAATCTCGTGTCTGAATGTTTACAAGCACCGCGTGTGCGGGAGCCTCCTGCCAACAAACAGAC

AGAGGACCGAGCGCGGCGCGGCAGCCCCGGAGCAGGCGGCGGCGGCGGCCTGGCCTCGCCCGGGC

CTTGCCCGACCTCGCCGCGCCCCAGCCCAGCCCCGGATCGCCCACCCGGCGCCCGGCGCCCACCC

GCCAGGCACGGCGGCAGGCCACGCAGTGTCTCCGCGCCAGCCTGGCCCGTGGTCCTGGTCCGCCC

CCAGCACAATGCCGAGACCTCTTCTCGACCTCCCAGACTGCGAAATCGGCTGGGTGAAACTCGGC

TTTGCAAAGCATTTTTATTTTGCAGGGCAACTGTAAAAGCGCGTTCTGCGCCTCCCCTCCCCTCC

GCCCTGGGTACTTTCTCAGACGTCTCTTGTCCACAGCTCGGGACCGCGAGGAGGTCACCACGTGC

TTTCCCTGCCCACCCCCCACCCCGCCCGGTCTGGTCACCAGTCCCCCTGCGCCCCGAGCACGACT

AGGCCAGGTGGCGGGGTTGCCGGGGAAGGGCAGGGGAGAAGTGTGTTTGAGTGTGCATTTTAAGG

GCGCTGGATCCTGGGACCCCGAGCACTTCACCCTTTGGGTCTTGCCCTCTTCCCCAGGCCTGGCT

TGGTCTGAGGTTCTTGTGAGTCTGTATAAGAGCTGGTGGTGGTGGCTGTCTCCCGCTGACTGCGC

CTGGAAAGGCGGGCGGTGGGCACTTAGGAAAGTTTGGCAGCAAGGGAAAGAAAGGCGTGAGGGCC

CACATTCCCCCCCTACTCAATTTATGATTCTTACTTTAAATTTTTGATGCAGTTTTAAAGGACCA

CCTATACTTGGTTCTGTGTTTTTTTAAAGGGGTGGTGGTGGGGGGTGCGCACAGGGAATTTAATT

TTTCACTGGGCCCTGGAACTTGTCACACACTTCGGAAGCTCCCCCACCCCGGCACGTTGCGCGGC

CCTCCCTCTCCCCACCCCCTCGCATCCCTCCCTCGCCGCTCTCCCCCGCCCCCAACTCCCCCGGC

CGCGCCGGATGCGGATCAGACGCGGCGCGCGGCGGTGTGAAGTTACAGCCCGGCCAGGTACCGGC

GGGAAGGAAGGGCAGTGTTCGCAGGACTCGGGAAAGTCAGGCCCTTCTTCGGAAGGATGCAGTGG

GGGCTCAAAGGACAGACCGGGGCGCGCAGTCCAGGCTGCTCCCTCGTACCCCTCTCCCTCCTGGG

TCCATCTTGGGACACTCTAGGCTGGGAGGGTTAGTACCCCCTCCTCCTGTCCCGGGGTTAAAGGG

CCAGTTTGGGAGGGGGTGAGGGGGCCACTTCTTTCTGTCCTCATTTTCTGGGTGCTCAGAGGGGG

CAGGAGCCATCCCGGTCCTCAGTACCACCCCCCCGCCCCCCGCCTCTGCTATGTGGGCTGAATGA

GCCATTCGGTCGCTAGGAGGCAGAACAAGATCAAGAAAGCTCAGCGAACTTGAACCTGTACCAGA

GCCTCCCCCACCTCCTGCCCGGCGATTCTCGTCCGGGGAGGAACGAGCTTTGCGAGGGTGGGGGT

GGGGGGAAAGAACGGTTAGGCAGAATTCCCTTTCTCTCCCCCATCACCCCGTATGTCTTTGTTCT

TCATTTTGACTTTAAAAATGCTTCTGGCCGGGGCCGCGGAGAAGCGACCGGGCGCGCGGCCGACA

CCCCCGTGCGCGAGCTGAGACCAGCGCGCGCCGGGCTCGGAGCACGGTGCAGTTTTCGCTTTCTT

TCGGGGCCGGCATTTTTGGTAGGGAGGAACCGGGAGTGCGCGCTCTAGGGCTTCGGGGCATGGCC

GAAGAGGGGGATATGGCAAGTTTGCACTTGGTCTCCAGCCTCACTTCTTCCACCCCCTCACCCCC

ATGCAAAGCACAGACCTCGGTGGCCTCGGCTGGCTTGCTGGGCGGCTCTGCAGCCCGACACCCCC

CCTCTCGCCTCGGAGCTCGGAATCACAACAATAGTAATAGTTATCATCATAATGATGCGGGCAGG

CAGCGTCATTAATAATGAATAACCGCAGCCGCCGCCGCGCACACCCAGTGCCCAGAATTGCGGGG

GAAATGCATTTGCAGAGATCCCCCAAAGTAAAAAGTGTAAGCTTGTGGACACAGAATGAATCTCA

GGACCCGCGCTTGAGGTGTGTGCGGAGATACTGAGACTGCACCAGGTTAACCAGCCGGGTTTTCC

AAACCTCACTTCCTTTTTCACCAACTGGCAGGCCCAGGGAACCGTCACCCCGCGGCCGAGCTGGC

CGAGCTGGACGGGCATGGAGGCAGCAGTCAGGGCCCCTGGCTGCCCTCCGTCTCCGGGCCCCCGG

GCCCCAAGGCCCCGCGGCCGCTGCTGCACGTGTTCGCAGCAAGCGCGGCGGGAGCCTGCAGCCAG

CACGCTGCTCGCTTTGTGCCTCAGAGTCCCCGCGCCCAACTTCACTTTCTGCACGGTCCACCCTT

GCCGGGGCCCCTGCCCCGGGCCTGTAGCCCCCGGCTTTGCTTTTGTTTCTTTGCTTTTCCTCTCT

GAATTTCAGCCTCCGTTTGCTTCTTTACCCTGTTAAGACAATCAAGGAGAAGGACTTGGAAAGCA

AACTTGAAGACACATCTCCCTTTCCCCCTCCCCCTCCGCTCCCCGGCAGCTCTCGTTTTGCTCGC

TCCTTACCAACATTTCCTATAAGGATTATTTTTTTCCCTTAAATTTATTCTTTTGCAACTACACA

GAGAGGAAAGAGATCTCAGTCTGTCACTGAGACATTGAGACGTTCCAGGCTGTCTTGCTGTTTGA

ACGTAGAAGCATTTTATTTTCTATTTCTTCCTCCCCTCGTAGAGAGAATTCGCGGCTAATTATTA

TGATTATTTGCCCACTCCCTTCCACTTCAATCGAGGACTCCCTGCTTTGTAGCCGGAGTTTAGGC

CGGAGCTTAGAAATGTTGGTATTGTTGGGGCGAAGGAGGATGGAGTTGAATTGAGGGAGGGGGTA

AATGGCTGAGGGTTAGGAAGGTTTTTAGGGAAAGGGGAATTTGCATTAAAATGCAGAGAAATTAT

CAGATGCCCAGAAAGGAAATGTTGATTGCCACTGAGAAAAGATGTCAATGCAAATCAGTAGACTA

CACCATGAGAATTGTATTTTCATATTTTCTTTGTGTCCCACTTTGTCTGATTTTTAATAATATAC

CAGCAATGATAAAAACACGTTTTGGTATTTCTCTGAACACCACTAGCCAAATGTTTTGCAAGGAG

ACCGATGTTAAACGTATTTCATACATTAGAATATAATTCTTGTTAATTAGCAATAATTTACGTTA

AGAGCATAGAAAATGTTGAGGTTACAGGTTTTATATCTGTACATTTGATCATCTTGTTATTTTCA

AGAACTTTGCCTCCTATAAAATTAATTAGGTGAAATGTGGAGGTGTAATCAGCAACCTCTGAATT

ACCACTTCATTTCCCGGTTTTGATTGTAAATCAGTTCAGTCACTACATTTAGAAGACTTTAACCA

AGTCTGTTTTGAACCACATTACCTTTAACTATTTGATACCTAGGAGAATATTTCCTTTTGCACCT

AAATAATATTCCCACTTTTAGAAATGTGTCAGACCTTGGGAACAAAAAAAAAAAAAAAAGAATCT

TAACGGTGGAAATAAAAAATTTTTTTTTTTGCAAAGGTTCTATGTACTAGTAAGTTTGATAAAAT

ATTTTCCTAAGTCTTCCTTCAGTCTGTAAACCTCAGAACTTGTAGCTAATGCTAAACAAAAAAGC

CACATTTATCAATGTGTACTTAAAATCCTTAATTCAGACAACAGGAATATTTTGAGAATGAGTTC

CCTATTCCTCACTTGGTCAAAATGGAAGCAAATGTAAGAGAAGAATGACATTAAGGCACAATGCA

GAGGCACTTCTGTTTGTCTTCTTTTATTTGAAAAGTATGCATATGTATTCTGTATTTATCTTTTG

GCCAGTATGTTGGGCAAAGAAACATAAGTGCTTACTTTACTGTCTTTATTAGTAGGAATATAACC

TTCATATTCCTGTGGTGACCTTATGTTAAATTAGGAGGAGTACCAGAGGCTAGAAATTATGAGAT

GTCCTACTTGAGCACAGGTGCAGCTAGGCAGGGCTCTCTCAATATTATTTCACCTAGCACATCTG

GGAGTTACTCCAGATCTTCCCCCTCAATATTCAGCCTGGGTAGGGTTGAAATAAATTTAACCTGA

GTTCACTGGATTTTTGCACTTTATCAAAATCTGTTCCAATATTCTACACTCAAATTAAAATCTAT

TTTTTGATTCTCTGTGGCTTTAAGTTCATTAAATGTAAAATTGGCAGCTTGCTAAAGAAGGTCAG

ACTGATTAACTGTTTAAGACTTGTACATTTTCTGCTTCAGTTTTATTAACTGGCAGCATCCTGGA

TGTTTTGTATTTTGTGATTTTTTTTTTTTTTTTGATAGAGCAAGCATAAGATTTCACAAGCAGAG

ACTTACCAACTCTCTTTTCCCCTTTGGAAGCTTAAAAAATGATAGAAGCTGGTAAAGTAGATGCT

GGAGTATTTTAGTACAAAGTTAAAAAAAAAAGCAAACAGGAAAGAAAGACATGTCTACCTTGTTA

TACCATCCGCTGGTGATTATGTGTGCAGAAATAGTCTCATAATGAAGCATTTTGGAGCTCATTCA

GAAAATTAGTCCACTTTGACAACATTAGGCGAAGTATTTCAAGTCTAAAGAAAGGACTTCTCAGC

CTTGCTCTGAAATGTGGTGTTTGCTTGACCATTCTGATTTTTATATCATAGATGCCACCAAGTGC

AAACATGTTTAGAATATTATAGGCATTCCATTTCTCAGAATAAAAAAAAAATGACTAATTGGCTT

ATTTTCTTAAGTACTCAAAAGTATCCCATTTAGCTAATGTGTCTGAGAAATACTGCCCGTGCATT

TGGTATTTCTTTGATTTTGTGGCACTGCTGAGAGTGAGAGCAGAAAGGTTTTTGGCAGTGTGAAT

TATGCTGCGACATGATTATTATTTAGATCCGTTTCATAGGTGCATGCAGTCGTTTTCTTATTACA

GCAGTGTAAATGTGGCACATTTTTCATGTGACATAGTAGCTTTCTAATTTATGAAGCCATGTCTG

TTTACTTAGGAGTATATACATTCACACACAAAGGGTGTGTGTGTTTATTCACCTCTCCTTTCATT

CTTTGGCACAATGGACAACTTGGTGTATAGGAAAAAAGAAACAAATTTGGTTTCTATCCACTTTT

TTTTTTAACCAGTTTTTCTTGTAGTTATTATTTAAGCTTTCTTTATGTTCCCTGTGTTAACTATT

TAAGTAGCATTCTTTCTAAACTTACAAACCAGACACATTTGTTGCTGTGGGTGTGTGCATGGGTA

TATGTGTGTGTGTGTGTTCTCTGGAGTTATGCAAGGAAGACTGTTTTCTTTACATATGTGATGAT

TTGCCTCATTGACAAATTTGCTCTCTGGTTGATAACCTTCACATCCTTGTACTTTTTGTATGCTC

ACATTTTCTGGGTATTATATAGAGAAGCCTAGAAACACTTTACATGATGTGGTGGGATGGCATGG

GGTTGAGATGTGCTTCTCCCCTTTCTGTCCTCTCTGGCACTCTAATAATTGTGCTTTTGTTTCTC

CAACCACAGCCGAGCCTCTTGAAGCCATTCTTACAGATGATGAACCAGACCACGGCCCGTTGGGA

GCTCCAGAAGGGGATCATGACCTCCTCACCTGTGGGCAGTGCCAGATGAACTTCCCATTGGGGGA

CATTCTTATTTTTATCGAGCACAAACGGAAACAATGCAATGGCAGCCTCTGCTTAGAAAAAGCTG

TGGATAAGCCACCTTCCCCTTCACCAATCGAGATGAAAAAAGCATCCAATCCCGTGGAGGTTGGC

ATCCAGGTCACGCCAGAGGATGACGATTGTTTATCAACGTCATCTAGAGGAATTTGCCCCAAACA

GGAACACATAGCAGGTAAATGAGAAGCAAGGAGAAAAGCTGTTTGCATGTTTTCTTTTCATTTTC

AGAGGTGCTGTAGCCAAGCAGTAAGGAGTTGTGAAGTGCTTTCTCTATTACTCTATGTGACTGTC

CATGACAGCCCTGTAATGTTAAAATAATCATTTCTGTTGCTTACGTCCAGAACACAGAAAAATAA

ATATTTTCCACCTCACTGAATCAGATGTAGGCAGGATAGGTACACACATCAGACACCTTCTCTCT

GGATCTGTCGATTTTGGATTTCTTTTCTTCCCCATCCCCACCTTCTCATTTTGAAGTATTGAGCT

TTACTACACCTAGTCCAGCTTCCATTGTCCATTTCCAGCCTTGGTGACGTGTCAGAGGCAAAGTG

GCCATATAGGCATTTGCAGTTCAGCCAATGACTTGTTTGACTCAGAACATCTGGCCAGGCCTCCT

TAGGGGTTCAGCTCGTTCTCAAGGCTTCCCTGAAGTAGAGTGGGCTGGCAGGGTAGTTGGAGGTG

GTGGAAAGAGTTAACTGAGCTTCAGGGCTAGCCTTGGATCCATATTGGCTGTCAGCCCGGATGGG

GCTGTAATTAAACACAGCCCCGTGGTGGGATGACACCATGACCTTGACTTTAAGATGCCATTTTC

GACTGGCCAGGCCAGAGTAGAGAGGGCAGTTGCTGAAGCGCACAGACATGCTTACTCGAAAAGTT

TAAGGGCATGTTGGAAATTTCAAAAGGTTGGTTTGACAGGAACGGCTGCTCCCTGCAGCCTGCCT

CCTCAGCTAAATGATAAATGCTTCTCTGTGCTCTCTCTTGTCTCTGATGTGGTTTTGACAGATGT

ATCTTGATTTTGTTTGTGGTTTACACAGCCACATGTCACCCTTACAAATGTCCAGTCCAGACTCC

ACTGTTTCTGCTATAACACAATGTAAAAATTTTCTTGGAAAAATACACACACGTATTCAACAGCC

CTCCCTCCTTTGGTTAATTTTAGCAGGGAGGCAGCTAGGTGTGTGGGTTTCTCGGCAGCTCAAGG

GAAAAGGAATTAAAGGCTAGCAGTGGGACTTAAATTCCCTTCTCTAAGTGATAAACAGTAACACT

ATATAGTGACCCTCAAAACATTTTTTGCTTGAGCATGTTAGACAAAAGTCAATGCAGATTCTGTG

ATGACAGACATGCCATGCCTGTTGGTGGATCGCTTTCTTCCATCTACCTACCACCCAGCTCCCGA

AAGGCAAGAGGTTTGTTCAGTTTTAGGAAAGGTAGTGCATATCATGAATTGATTCACTGGAACTT

GTCTCTCCGACCTAGTTTGACCACAAAGTTGAACCATAATAGGTCAGTGGTCTAGAGGGGATTAA

ATGTCATATTATTTCTCCTCTCCCCCTCTAGAATTTGATCATTAAAACCAAACATGGCATTTTCT

TTCTTTTTTTAGTGCTTTCTGTGATAGCACTCAGATACTTTCCCTTTAGTGAAATGGGAAATCTG

CTGCTAGGGAAGCTGCATTTGTGGAGTGTATTTCTTGAATCCACCACATTTACCTTATGTGACAT

GTAGGTGAAGATTTTATCTCCCCTACCCCCCAGCAGGATGTGGGAATGACCATTTCCATGTGTTG

TCTTGTGACTGGAAGGAAAATGAACAGAAGTGTAAGGCATGATTAATGAAGCAAGAGCAGGCGGA

AGGGGATTTGTCGTCTTCGGAGATCCAAAGCCTTGCTAAATCACCAAATATGGAGTAACACTTGC

GTGATGTAACATCGTATTTACATATCGAGCTGCTCGTTTAAAAGACAAAACACAGTGTCTGTCAA

GCAAGAATTAAAACCACACTTCTTACTGAGGTCCCAAATAGGTTATTCAGTCTTAGATTAACCAG

CTCAAAAATTCTGTGCCTCTGTATTTAGAGGAGGAATCTAAATGCTGGGGGGAAGGCCTTACATA

TAGTTAAGACTTTTACTGCTATAGITGTGAATCTATGTAGGGAAATAAGAGATATTTGCTTGAAC

TCCCTGGTTGTCTAAAGGTTCTGTTATTATTTTTTTAAAGAACAAGTATAATAGCAGAGCCTAGA

GAAGCCAAAACCAAAAGCAAATTTAAAATATATTTTATAGCGCTAATAATCAATCATTTAACTGA

GACGAAAAGCTCTCTAAGATGTCTAAGATATTCAATGGGCGCACAACAAGTGCTGTGACCCAGGT

GAGGTAAACCTTTCGTGCATGAATAATTACAAAGTCTTGATTTCTTTCATTGTGTTTAATCACCT

GTTCCCACCCTGGAACTGGCTGAACATAAATAGTGTGGTCACATCTCAAAGTGAGATGTCAGTAA

CTAGAATCACGACTTCTCATAATTCACAGTAATGAATTAAGAGTTTCCTATGGTGAAGTTAACAT

TCTACCATTGCACATAAATTCCGACGCTCTGGCCCTCAGGTGCCCCTGAAGCGAAGTTCTGGAAG

ACGGCTGTGTGTGTACCCCCAGCCCATTTCTCTAAAGCACGTCTGCACAATTCCAAGTCTGCTTT

TCTTTTTATGATGAGGAAGGAAACAATAACAGTAATCATTCAGTAGATATTTGAATTGTGTCACA

AAAAGAAAGGAGAAGCAATGCCTTGTATTAAGGAAAGAGATATATTGATGAATCTCTAGAAGAAT

GTGTTTGGCAACCACATAAAAGGTAGTCATTTAAGCGTGCTGGGTAGGAAAGGCTTTATTAAAGT

GATGTAAGTTGGATTTGAGTTCACTGTGAGCCTGTACTATTTTATAGGCAGGAAGCAAGAATAAA

ACAGTGACAGATCTTCTTCCTAAGATAAATAAAGCTTAGAATTCGGGACTTTCAGATAGGAGAAT

AAGGCAGAGTTCTTTAAATCTTGAGTAAAATGGTATGCATTTTCACTGTACTCAGGCCTCTCCAA

GCTGAGTTTTTTTTTTTTTTTTTTTTTTTTAGACAGAGTTTTGCTCTTGTTGCCCAGGCTGGAGT

GCAGTGGCATGATTTTGGCTCACTGCAACCTCTGCCTCCTAGGTTCAAGCGATTCTCCTGCCTCA

GCCTCCCAAGTAGCTGGGATTACAGGCGTGTGCCACTACGCCCAGCTAGTTTTTTGTATTTTCAG

TAGAGGCAGGGTTTCACCATGTTGGCCAGGCTGGTCTTGAACTCCTGACCTCAGGTGATCCACCT

GGCTTGGCCTCCCAAAGTGCTGGGATTACAGGCTTGAGCGACCGCACCTGGCCCAAACTGAGTAT

TTTTTAGAGGATTCTTTTTACCTGGTGAATAGATGGGTATGTGCTCCCCCACTTCATCCACGTAC

ACATATGAGCTGTACACATAGATGTTAATCAGGTTGCTTTTTTCATTTTATTTAAATATTCAAAA

TATTGTGTGATTGTGATCCATTGAGATCATTGAAGTAGTATTAATTTAGCTGGGAATTAGCAGCT

TATGTTGTGTGGGCCCAGTTCATCAATATGTGTGTCAAATATCCACCCTCAGATATCAGCAGCCT

TTGACTTGCAGTCAGAGCTTTCAATAGGGGTTTTGTTTTGTTTTGTTTTCTTTTTTTTTAGTCTC

ATATTTTATGATGGGGGGAAATATTCATGGAAGATTACTGAATGTGAAACTGCTGTTCCCTTATA

GAAAAGACCCAAACATTATCCCATCATGTCAGATTTGAGGTTTTGGCTTATTGCACATAGGAATC

TTTAAATTAGGTTTGGGCTGTCATAAAGTTAGCTTTTTGAGAGACTAGAGAAAAAATATGACAAG

TCCTATAAAATGTAGTAAAGTCTGCTCCTGTTGATATATAACATTTTTTCTCTTTAAAATCATGA

ACATAGACATTTATATCAGGGTATTTAAAATTATTTGCCTAGACAGTATAGCTGGTATTTAGATA

ATGATATATCAGACAGATACTCTAAAGAAGGGAGATATAGTAATTCAAAATGGAAATACATTAGC

ATGCTCTTAAAAGTAAATCAAATACAATATGCTTTTCAGAATTTAGAAAATGAACTTACCTTTTC

TTTTTGTATCCATTCTGATTCTCTCCTAGCTCAGACTGAACTGGAGGATGTATTTGTGTACCTTA

TGGTGTAATTGTAAATGAGACTATAAATTATAGTATGCTATTATGACTACTTATTTTTCTTTTCT

CTTTATTTATGTGATTCTGAATAAAAACGACTGACTTCTGAAGTGAATTTTCAGCATGGCAGTTA

AAACAAAAAAACACCACTACCACAAAAAACAATATACTGGTGAACATTTTACTTACCTTCAAAAT

CCAGAGAGTAGAGAATATTGTTTTCTAATAAGTACCTAGGATTTTCATAGGGAGCCTATGTTTGT

GAGGCCACTATCCAAAGACTAATGTTCATGAAACTGGGAGTCCTATATACAAGCTGTATTTGTAA

ATAAGACAGAGAAAGGTTGTGAACTGGCAGCTTGGATGTTTTGTCAAAGTACAATGTCAGAGAAA

CTCTTTCTAAGACAAATTGTAAATAGAACTGTCACAGTGATTGCATGATTGAGCCGCAGAAGTGT

CCTACAATTGTTGGCATTGTCAGGACTTTTGAAAGCTTAATTAAACACAGTGGCCCGCATGGCTG

CTAAACTTACTAAGGAAAGCCAAAAGGAAAAAAAAAATATATCTAAAATGTAGAAGATCCTAAAG

ATCCCAAACTTCTTCAGACATTACCCTTGTGGTGACACAGAAAAGATGCATTGTGCATTTTCCTA

GTCATCTTTTATAAATAATGTTTTGAGAATAGGTCCACGTGATATGAAGATCATCCTGTGTGTGA

TGTGGAGATTGTGTTAGTTTTTCTGTCTCCTGCTGTTACAGACAGTTAATGTAAAAATGGCCTTT

TATTGGAAACACAAATATGTATTCACTTCAAGAACAGGAGCAGAGGGGGACAAAGTTTCCCTCCC

GTTCTCTGTGTTTATTCTGTGAAAGCTTAAAAAAACAAAAAAACAAAATAACCACACACACACAC

ACACACACACACACACACACACACACACACACAAAACCAGTGCTGTAATTTCTTAAATCACCCCA

TTCCTTGTTGTGTTGCAAGTIGTGCCTTTACTATAAAGGATCTGAAATATGTTTTGCACACCTTT

CTCTTAGTGAATGTGGCATATAATTGTGGAGCTGCACATGGGCTGGAAAATGCAACTGGGTGTAG

AAACGTGCAGGCAGGGTCAGGACAGGCAACCTTCAGCTCAGGGAGGAGGCGAGTTGGATGCTTAT

TAATGGCATCTTTTAGAGTCCTGGAAAATCATTAATTTCACACTGCAGCTTCCATGTAGTTTGGC

TAATGTGGGAGTACTAAATTGGGGTACATAAAAAACATGCAAATCCTAGGGAAACATTTTTTAGA

TTTTTGTGATTTCTCAATGAAAATGTTTAATAAAGGAGAATAGGTGAATGGTGGCTTTGCGTGCT

GGTCAGTAAGAAAGGAAACAAATTTTGGCTTTCCTTTGGGGGGAAATATTAAATTTAACCGAAGT

AGAAAGCACAGCTAGGGAGATGCACCAAGATTGCGTCACTGGATGTTAATTTAATCTACTTTGGT

TGGTCTGTTCACACCCTTTATTGCACAAAGAAGTCATTTGACAAAATTTACCCCAAGCCCAAGTC

TGTTTTTACATACAGTAGTACCAGCTTTGTGCAATAAAAAGCACTTAGCATCAAGCTGGACCCAG

CCTGGCACCTTGCCACTTTTTTAGCATGAGATTTAATCACCAAGCATCTTTAGTACCTTTCTGCT

TGTTCAGATTTCATTTGGGTCATGGCTATGTCAGCAGTGTTGTTATTTCAAGGATTAAAAAAAAA

GATTCTAACTTAGAGCCCACTTTTAACATTATTTCAAATCAAGCAGGTTTTTATGTTATGTATCA

ATTTGGATGACATTAATGAAGTTCATAAAATATGTTCAGACTATATAATTTAATGGATAATGACT

ACTATTTTTATTTGTAATACAAATAGGAAATTGACTGTTGTCTCCCTCCCTCCTTGGTTCTTTTC

TCCTACCTAGGTAAATGGGCATCCTTAAACAGCTTCTCCCCTTTACGACCAGGGTATAGAGCACT

GGCCAATATCAGTAAATTTACCTTTGTAATTTGCCACGTAGTTTTTACAACATGACCTAATTAAT

TTGAGCACGAACCATATTATTGCTACTGGAGTCATTTTCTGTCACAAACTTAATTTCCAGGAAAT

GTAACCTGACAAATAAGAATTCTTTAGCTCTCTACATGTGCTCCTAGAGACCAAAGGCAGATTTA

AAATAATAATAATTTTAAAAGTGCCAGCATTATTAAAGCCAGTATACTTGATGCCAAACTCAATT

TGAAGCCAGTAAACATCAGACTGTATTTCTAATCAGTTTTAAAATGTAACTTATTCCATATTGGG

TTCATTGGAATTTGTCTCCCTGCTTTTTACTGGCCAGCTGCACTCCCTATGCATTTTTAAAACAT

TTCAGCAAAGGCTTTTGCTGTTCTTAGCAGGGTTAGTAACTTGGGGTCTATTTCTGAGCTCATTC

GTCATTCTGCAATGGCATTGAGTTAGGTTGGCAAGGGAAGGATTTGAGGCATGGGGGGTGGTGAG

GTCACTTCTGATCCCAGCAGGGAATAGGTGAGCTTCATTTGCCTTTACAATAGGCGCACAGTTAC

TGCACCTTGGAGGAGCTCTCAGGTGCCGCTCAGATGGGCGCATGTAAATGCCCTGTCAGATGCGG

AGCTGGAATATTAATGCTTCTTCCACCACCACACCATAATAAAGCTGTACACAGCAAGCTTAATA

TGCAGCTAGTCTGGGGAATTGTATAAACTTAGATAGCCCAGTGTGAAAGACAGCAATGGAAAAAT

GCTCGATATGCCACAGTTTCCATTCTTGTTCTCCTTTGATCTATAGCGAAATGAAAACATCATCC

TTTTCTTCTCTTGGAGTTGTCTCCCCAACTCTGCCACCTCCCAATTCACCACCAGAATTTTTTTG

CATGTGCTGGTATGGAGAAATGCAACATAATTTGTTTCATATGGTTAATTACAGGCGTTTGAATA

TTTAAAATTTTAAATAGCCACAGTTCCAGCTTTTCCCGTTAAAAGTATGTGATTTGAACAAAGGG

AGTACAGTGTAAATATTTGTGGTGATTTGCAACACCCCTCTTTCCCCATTACACACACACACACA

CACACACACACACACACACACACACACACAGAGAGAGAGAGAGAGAGAGACATTCAGTTTAAATC

TAGTACTGATCTAAAGGACTTCTGTACCTTCATTTGTACTTTTTTTAAAAAACAACTTTCAACTG

GAATTCCATTAAAATATTTCACCATTATATTTTTGAGTCCACATTGCTTGAGGTTTTAAAGAAGA

TTTTTATAATGTGTTCCTTTAACAGAATCAACAGCTGTCAGAAGCAGTTGTGGTAGATCCACAAA

ACGTATAAAGAAAAATACACGTTTCCTGAAACAAAACACTTGGAAAAATAAGCTGCTAAGAACTG

GCGAATTAGAAGTTTGCAGACAGGGAACTGAAGTGTCATCTCTTGGTTCACCCTGGAGACTGATG

TGAGTGGATCTGATGCAATGCTGCTGGAAGATTTACCTGCACAGGTTGCTCCTCTAAGGCAACGC

GCAGTGCACGATTGACGTATGCACCAGAGCTAGGCTGGGCCTCAGCTCGCTCCATCTTTTGCCCT

TTTTGATCTCTTTAGATAGATAAAATACCAAGTTCTCAGAGTGCTAAACAACAAATTATATATAC

CTAAAGGTGAGATGATCAGGTTTAAACTTCCTGTAAAAGAGGCGAGAAGGCGCCTTGCACACCCT

TTTCCAGATAGGGCTGGCAGCATGTTATTCAGAACTGAATCAGTCTCTGCCAGAGAATTCCCAGT

GGGAACCTGGAGCAGGTATGTTGATGAAGGGGATACCTGGGGACCTTTGGTCACTCACAATGAGT

TTTTGTTTGTATTCTCACTGTTGTTAGCATTGCCAATGAACAATTGCACCTACAATTTGATTTTA

GTTTTAGATAGAGGCGAATCCACTGATTAAAAACTCCCATTAAAATAAAGAATGGAATTATTGTG

AAACCTGCAAGGGTGCCTTCAAAAAGAAAACCAGTGCTGTTGTATACCTACCTCGCCTTTCTATT

TGCTTTTTGAACTTTCTAAAAAACACAAGGAAGCTTTTTGCTAAGCATCAGGGCATTTAAATTTA

TATTCATCAGTTGTTCATTTTCTTAATATGTAATGATGCATAAAAAGGCTGCAAGGAAATCACAT

CTGTTAATTTTTAGGGAAATAAAGTGTAGCTTGGATTCTTATGTTGGAGCACAAAGCACTATGTG

CCAAGTCTGTTCCTGTACATTTTAAATATAGAGTTTTAATATTTGGCCAATCCCTGCACCTCCTC

AAACAAAAACAAACCTCAAAAAACTAAGAGAACCAAACCTGAAGTATTCTCCTTCACCAACTCAA

GGTATACCATGATTTTATGATTTATTTACATTTAGGGGGGAACCCCTCAGTGAACCATTTACTCC

CCATTTTAACTCCCCTGCCCCGATCCTTTCAGTTTCCAGTTAAAACAATGCATTAACCAATGTTA

AATCTTAAATCTCGTGAGTTTCTCTCCATCACACCCTAATATTTTAAAAAAATTATTCCTTTACA

TTTAAAACTGAACATTGGCTACTGAAGAATGATTTAAAGGCTGAAAAAAATTTTAATAATAAATC

GTAACCTTCTCATGTTATGTTTTTGTTATGTTAAGGAGAAAAAAATCAATAAGGAAAAATTTAAT

TCTGATAAAGATACTCTTGGATCTTTGAAAACAACTGCTGTCCTTTTAACTAAAACATTTGAGCA

GCTTCAAAGACTATGTATTTCTTCTGATCTTGGAGCTGTGTGACTGGTAGCAAGAAAGAAAAAAA

ATCTTATTCTACATACAAGTGGATTGCTTAACAAGTCAGCACAGACACGTACTTGTTTGTACAAT

AGAGATAAAAATTCCTGTATAAAAATAATTCAGCTGCTGACAGCAGGCATTGTTGTTGGACCTGT

CTTTTGTGCTTGTCCCAGCTCTGGGTCCCCCTCCCCTCCTATCTGCTTGGGGCAGCCTGCTGCCT

GCACACTGCTGACCAGAAGTTAATTGCTATATATTAAGTATATAGGTATTGTATTTAAAGAGGAA

TATCTCAAGGCTTCCTATATGCATTCCACTTTACTTTCTGATGTGATTGCGGTGTTGCCAGCAGG

GGGGTGGCAGGCAAACGCTCTAATAGGGAAAATCACTTGAAGGCAGTTAGGGGAAATTTGGCCTT

CAAGTCCCATTTGCTCTGTAGTGTAGCATTGGTTTCTAAACTTTTGTTTTTAATCTAATTCTGAT

TTGCCCTGTCACATCCCATATCAACCCTCATTGAACTCTACTCATGTAGAGTAACATTAGTGTCA

AACGGAATTGGTCAGGACTGTGGACCTGTGGCTCATACAGATGGTTGTGGATGTGGGTTCCATGC

AGCTCTGCATCCTATCCTTTCTAATAAATGTTAAAATGTGGCACATTTCTGAGCAGGGCCCAAGG

ATAAGAGAGTTAAGAAATCAGGGGGTAGTACCTGAGATTTTTCTCCCTTCTCTTTCCGATTTCCT

TGATAACATCCACATTTCCGGTAAGATCAACTCTAGGAGAAAGTCTGAGGCTGGGGGAGAGAGGG

GGAGAAGGGTGCGGAGAGAGGTTCTTGGAATATTCTTCGATAGCAGTTCAAATGAAATCCCCACA

GCAGAGAGCTTTTGGGTCTAGCAGTGGAGCGGTAAGCTGGGACACGTGGCCTTTCGAAGCTGTTA

TTCTCAGTCTGACTTGCACACCAGCTGAGATAGGACTTAACATATACTTTCTTGCTTTCACCTGG

GTTGGAGAGGTTGGGGTTGGGAGGAAGAGGAGGAGTTCATTGGGAATTCTGTCACTAGAATTTTT

TAAATGTCAGGAGGTTAGCAAGGTGTGAGTTAGCATTCAAGCAAAGGATTCTTCTCCAGACTAGT

AATTGGAAAGCCTGCAAATCCAGGTTCCCACGATACTCTCTAATAACTGGGGTGGGATGGTGGTG

GTGGGTGGACACCACAACTTTCTGAATGTCAGCTGATGTCTGCATGACCCGTTCACCATGGATTA

AATGCGGCTGGTGCCGAATGGAGGAAATCAGAAAGGCAAATCTCAAGCAACAGGATTTGCACTCC

TCAGAAGTAAACCAGACCTTGCTCCTCTCCCTCCTGTGCTTCTCCTTTCTTGCTGGTTTCCCTTT

GGAAGCAGAAACTTCTAAAATTAATGCCACTCCAAGCCAATGAAAAAGCTGTTTTTATACCACAG

TGGATGTTTACACAGGAGAGACAACTTGAGGGGGAAAAGGCTTTTTGGAAGGGTGGAGGGACTCG

TGTTAATCTGTTCTGTTGGAGGACTATGCAGTATTGCCTATGAGCGACTCTGGGCTGTTTTTGAT

AAATTACCATGTTTAGAGATAGGTTTGGCTCTTAAGGGCTTAGTTTTATGAACAAAGTCCGTGAC

GATGTTTGCAGCCTCTGTTTGTATCTTAGCCCCTTTGGCTTGACTAGAAGCTCTATGTTTAGTTT

AAGCTCAGTCTGGAAGATATTACAATTTTGCATTAAAAAAATGAGGAAATCATAGGAAGAAAAAC

CCTTTGCTTTTTGGATGAATCTTACTGATAATTTGCTAAAGCTCATTTGAATTTTAAGCACTTCT

TTAATCTTCAAAGGCTAAATTGCTTTATGAATATGCATGGTGTGGGCAGACTTCAGTTCATTACC

TAGTTGTAAATTCTAATGACCATTAGGTCCTTCCAGTAATTGCGAATTGTTTTGCATTTTTGATT

GGCCTATTAACATGTACATTCGGTGCACATCAGGCTGGCCTGTCAGCCTGCTGAAGGAGAAAAAA

AAGGTGAAAATTGTTTATAGCACCAAGATTCTTAGATTTTCAATCTTGCAAAATTGATGATGTAA

AAAAATTAAAGCAGTGTTTTTTCTTCTCAAGATTAAAAGTTCACCAAGAGATTTGACATATTTAA

TTTACATGATGACTTTGCACTCCTTCATTAATGTAATTTGCATATGAAGCTGTTGTTAATCACTT

TTGATCATGTTTTGTGTATTAGCTGCCTCAGTGGCTCTCCTCCTCAGATGCCCCAGTAGAAAGGA

GCAAAATGATGCATCTTCTTGCCAAGTTTCCTTTAGTGAATTGAGGAATTAGAAGTCTAACCTTG

AGTAATTACATATGTTTTATCCGTTTTCTTTTAACGTTAAGTACAGTTTGTGAACGTGTTGGCTG

GAAATCGTTCTCATTTGGGGAGAAGACTGTAAAATTTAAGTATATGATTGAGGCACTTCCAGATA

CATAGAGAAATATGTATTGCCTGTTTCTGTTCCCCACGAACATTGCAGGGCAGTTTTATTGTTAG

CAGTTTGATGGCAGGAAGCCTTGGCTATTATAGTGTATTAAGACATCAGGTTCCTCCTTTGGAGG

AGGGAAGGCTACAGAACTACAAACCTTTCTAACAATGCTTTAGGTTTCTTCTTTAGATAGATGGC

TGGCACCTAAAGGACTTGGGCCTGGGTTTGGCTGACTCTTTTATCTTTTAGATCAAGTAAGTTTT

CTCATTCAGCTGCTGCTCTGAGCTACAATGTGTCCTCCCCTCATCACCAAAGTATATCCTGGTCT

CCAGGCTCCCTGGGCTCCCAGTGTCTCCCTCAAGGTACACGAGTGCCCTGGTGGTGAAAACAAGG

TGCTAACTAACGGTTTCCGATTTTTGAGAGCCTGTGATTTTGGTGTTTGCCTTTGCTGTTGAATA

ACCTGTGCTGTATTATTGATGTTCATCTTTGGTTTATGAGTTTATCACTGGTTAACAAGCAGAAT

CAGAACAGTGTAACTGATATTCTGATTAAAACGAATGTTTAATGAAAGAAAATAAATTGTGATGG

AAAATGAACAGTGTGTAAGAAACATAACTATAATTTTAACCTCCGAGGGACCTAGCACTGCCCTA

CCGTGACTTCCATCCATACCATGCTAAAAGCATGCTTCAGTTTAAAGTTGTTAATATTCAGCTGG

GAAACAGTATCCAGAACACAAATAAATTATTAAGTGCATGAACTTTTTAGGCAGTAAGATGAACT

GATGGGGTCCATCTGTGAGATCCAGGGGCTTTTTATTTGTGTGTGTCGAGCGATTCTGCCCTCTC

CGACTTCACAGCCTTTGGTCTCCGGCCAACTGCATGCATAATTGATTCCACACGCACTATCATTT

TCTTGATGTAATTGCTTTACTAAGATATGATGAAATCTAATGGATAATTTGCTATTTGAAAATGG

TCAAAAAAAATCTTCATACTTTATGTGGGGCTGAGTGGGCAGTGGAGAAAGGGGTATTCAGCTGA

CCCGGTATTTAAGAAAACAAAACAAGCAACACTAACTTATGCATGCTGCTTCAGTCGCGTTGGCT

GTGGATAGGAAGGTCTTTGTGACATATGGAAGCCAGTGTATAAATCTCTCTCCTTCTATCTTGCA

TCACCCCCTTCATTCCTTCTCTCTTTCTCTCCTCTCTCTCTCCCCCAAACTTTACAAGAAAGGGA

TCCTAACAAGGTAAAAAGTAAACAATTTAGTCATCACAAGCCTTATTATTCAGTCTATCCAGGAG

TTTTGCCATGTCGGTTTATTTAACTTCCAGGAATGTAAACACTGACACAGCCCTAGAAGCAGCAA

GAAAGATTACAGTATTAGAGTTAAAAACGTGAGCATGGAGGAGCTGTGCTTTATACTCTGCTATA

ATAACACTTTACATTGAAACATAATGGTAAGTCAAAAGTGACTGGAAACTTCTGCTTATATGGAG

TACAAATTTCATTCTAATAGATTGGCATAATCTAGTGTACCCAGGGTAGATTGTTATATAATGGA

GAAACTGTATAAATGTCAAGTACACAAATAATTCTACAGGAAGTAAATAAAAAGTATTAGAATTT

CTTAAGTCACCATTAAATTTTGGTGGTGGGACAATCTCATTAGCTCCTTCAAAATCATGTGGCTT

TGCATAAGTCTTTTGAAAATGTATTTTCAGGGAATTTACAGATGGTGAAACATTGTTTTAATCCA

AACCAGTTAATGCTTTAAATCTACCTTTAAAAAAATTGTACTGTTTTTCGAAGTACTTAAAGGGA

GTGGAGGGGTAGAAAGCATATAAGTGAATCCATCTCACTGTGGCAAACTGTTTTTCAAGTAAAGT

CATAATAATGAACAACACATGATCTGAAATTTGATCAGCAAACATATCCTTATGCCAAGGAATTT

TCTTTTTTTCTTTCCTTTTTTTTCTTTTTCGCCATTCACATACCAAGGTTCTGTAAATCAGTAAA

CCAGGCAGAGAGTAACTATTGTAAGGGGGAAACCAAATCATAATACCCAGAGTGGCCCAGAAGCT

GTCTTTCTGAAGAAACATTAACGCCACCACCACCAAAAAAAGAAAAACAAAAAAACAAAAAACAA

AGCAAAACAAAACAAAACCTTTTTAAAAAACTGGAAATGACAGAATAGTTTTAAAAGGAAAAAAA

AAAAAACCCAAAAACCAAAAAGCAACAACCACCTTCTGACGCTCAAAACTTCAAACTATTAATAG

ACCACCAGTGAGATAGACTGTCTTTGTGCCTTGAAATGCAAAATGAGGGAAATAATTAGCAGAGG

AACAAAATTCTCAAAATTTGAAGAACTTCTGTGATTACTGGGGGTACAGTGAAAAGAAAATGCAA

ATTTCTTCCTGATCTTAATTAGATTCGATTGTGCGGTGGGTGTGTTGGATTTGGGGGGAGGGGCA

GAGGCAGGGAGTGCTGGGGTGAGGCGTGAGGCTGAGTGTTGTGGAGACAGGTTAGCAGGGGCCCG

GCGGTGTGGCAGGAACAAAGGCAGCTTCCAACGCTGGTGCAGGATTCCGAGCCTTAACCCAGATG

CTCATGGTGCCCTAGTCTTGAGTTCTTCATTTAGGTGGGCTTATTTCCCACTGGGTCTGGGGGAT

TTCATTTGTCCTTTGAGGGGCAGGGTGGACACTGACAGAACAGCTGCGGCCGGCAGAGAGGGTGG

TTAGGAAGAGGGAAGCAGCCTGTGGGTAACTTCCCGACCACATGGAAAGGCTGAATAAGACGTTA

TGGACCCTGCCTTGGGTACTGGGGTCAGCGTCTCCTGGTGGTGTCTGCACAGGGCCCCCCAATGC

CAGGGCACTGCCAAAACACGCTCTTGAGTTTAATGGTAGTGGTTGGTCTGAGTCCTGCCAAAGTG

TATGGAGCAAGTTTCATTGGCTGGACTTTCCCCTTGCATGAAATAATAAAAGCCCTGGCCAAGGC

TTATGAATCTATTTTTGTTTCATTAATATTATTTATTATGTATTTTATTAATATTTTTTGGAGGG

ACCTTGCTCTCATTTGACCATTTGTAGTTATAATTAATGCATTCCGTACTGGTTGTAAAAAGTGT

GCTTGCATTTAATTGCAAGTCAGGGTAAATTAATGGATATGATTTAAAACAAAACTCACTTAAAA

TATTCTTGCAGAACGCAAAGGAGGGGGCAGTCCCAGTATTTAATTTATTTTCTGGTTTAGTGTTA

GTGTGAGAGGGTCGAAAAGATTCTGTGGGTCCAACGGGATTTGTGTCTGTGTGTGCAGGACCGTC

GGGCAACACAGAGGGAGGAGAAAAACCTGGACCGGAGTAGGGTAGCCAGGAGCTCTTTTTTTTTT

TTTCTCTAATTTCTGAGGTTGCCAGGAGGGGCTTAAGCAAAGTGGTCAAGTCCATCTGCTCCGGA

GAAGGTGGTAAAGAAAAGAGGTTAGTGGCAAGAGGGAAGGAGCACAAAGGGAAAATTGTACATTG

GGAGCGTTACTCTCCCTGGCCATGGTGTAGCCAGACTGGTTTAGCAGACAGAATGATAGATTGTT

TTGTCAGGGGTCCCAGGGTGCGCCCTGAACTTGAAGCACTTTGTTTATCTTGAATAGAAAGGGAA

AAGCGCAGACATAATCGATGTCTAGTTTTTAGGAGCTCGAAAGAGGTAGGAGAACAGAGAAGACT

CAGGAGGGGTAGTGGGAGGTGGGGGAGGTGCAGGCCCTGGTTGTGGTTGTCCATTAACAGATGAA

CTTGGCCGAGGGCCAGGCTTTAGATGAGAGCGTGTCAGGGCCCCAGTGCAGCCAAGCCTTTTCAG

TGTTTTTTTTTTCCTTTTTCTTTCTTTCTTTTTTAAATACCTGCTGACTGTACATCAAATGCTCC

CTGGTCTTTTGGCTAAAGGCAAAAAAATAAAAAATAAAAAAAAAAAGAGACGCACAGCTCAATTT

TTTCCCTCCTCTGAACCAGTTGAGGCCAGTCTTTTGGCTACATATGCGGGTTCTATCATCTTTCC

TGGCTTGCCGTTGGGAAAAAAAGTTGTGATAACGCCAGTAACCCGAGGGCCAGATGGGAAGGGTT

TGGTTGTGTTCAGGCGACCAGGTGTGAGAGCTCGTGGTGCAGTGGGGTGGGGCGTGGCCGGCGTG

CCTGCGTGTGCAGGTAAGAAATCAGTGGAAACTCTTTTTTTTTTTTTTTTTTAAATGGCTGAAGT

TTAACTTGTTGGAAGGGCCTGTGAATTAAGCTGTCGGTGGCTGAGAACGATAATATGCAAGGAAG

GCTCAAGGAAGGCTCAAGAAAGGCCAGGGGTGGGGAAAAGGTGCTCTTGTTAGAGGCGCAGCCTT

TCCTGGGCAGGACCCAGGACCGATGGCAAACCCATGTGTTTGGGCTTGTTTTGTTCTCGATTTTC

TTATCTTCTTGGCCTCTTCCTGTGTTTTTTAGTTTATTGTGACATTATGCATTCATATATGAATG

TTGGCAAGCAGGAGTCATCATCCCAATAACTTCCTGACATTTTTAGCTCTTTTAATGTGCAGTCT

TTGCCCTCCTGCCACAAGTGGCGAAGTAATTGAATTTCCCTGTTACTAACTGGCAGGAGGCATGT

TCTAGTTCCCACCAGAGGAGCTGCTGGGGCTAAAGCTGGGTTCATAGAATCCCACCTAGGGGACA

CCAGGGCTTTCAAGTGGTTTGGGGACCTGTCTGAAATGATATTCACACAATAAAAAATATTTTTC

CCATCATAGACTTGAAAAGGCACCATTGTGCACATCTATATAAAATGTGATAAAATCACATTTAC

TTCCCCTGGCTAGGCCTCATAAGGGAGGCAGGATTTCCTTCTCCTTTTCTAGTAGCAAATAAAAA

CTGGGAAAATTTGGGGGCCTCTGGGTTTATCCCATGGATACCTGCCCCCGCTCCCGCCCGCCAAC

TCAGCCAAGCCCTTAGAGGCAGTCTTCTCTCCCACCTAGATGTCTTTGTAACCTGAGCTGGTAAG

AAAGGGAGGAGGGACAGAAAGAGGGGAAATATGCCCTTGACATATGATGTATCTTCTTTCTTTTC

TTCTTCTCTTTGATTACACGAAATAAAATGGTTTAGGCTGAGGGTAAAGAAGTAATACCATTTCT

AGTTGTGCAACCTTGGGCAGATTTCATTCCCTAAGCCTCCGCTTCCTCAATCTGTAAAGTGGGGA

GAATCACGGGGCTTGCCTCATAGGGCCTTTGAGCATCCTATGAGAGCATGTGGGGGCGCTGGGCT

CAGTGCTGGGCACATGGTAAAACATGTCACAAAAGCTCATTACTATTACGGTTATGACTCATGGC

TTGGAACTGTGTGCTCCTGGGGTCTCAAAGTAGTTCCCCCATTATGGGGTGAGCAGGTTGGGATG

AGAGAAGAGCAGGGCAGGTGGGGGTCTAAAGAGCTCAGGGTCTCATTATGTTTCTGGTGGCAGCT

CCCTCGTGGGTGGGAGTCCCCTCTCCCCATAGACGTGTGTTGCCTTACGAGAGGCTTGTGCCTGC

CTGGGTGTGTGACACAGTTACTCTGGGTTCAGATTTCTATGTTACTGCTAGCTGGTTGGGAGAGT

CTGAGGGAATCATTTCACCTCTCTGTGAAATGGAGATAACTCAAGGTCCCTTACCTCATAGAGTC

CATGTGAGAAGTAAATGAGGGAAAGCACAGACATTACTCGCTCCGGGGGCTGCACCTCCAGAATT

GCTGTTGTCATTATTACCATGTGTCTGACACATTGATATTCCATCCCACAACAACCTCGGAAAGG

AAACACTCCCATTAGCCTCATTTGGTAGAGGAGGAAATTGGGGTTCATCAAGGGTTAAATGACTT

CCCTGAGGGTCCACAGTTGTTCAATCCTTTGGCCTGCGGCCGCCACCCTCTGCTACCTCTTCAGT

ACGTTTGCAGCTTTCTTCAGCGGTGCCAGGCAACAACTGGGCAGGAAGCTCTGGTGCTGGACAGT

TGTCCCTCCCATGGGTTCTGTGGTCAAGTTTTTCAATCTTCTGGGAAAGAGAAGAATGTTCCCCT

CCAGTTCTGGGCATATTGAAGGAGCACGGAGCTGTTGGGAAAAGTTGCAATGTAAGGAATCCTGC

TTTGCAAGTAGTCATTTCCCCATCTGTCCAGAATGAGCCTGAAATCAAGTGAGGGTCCTGAGAAA

CAGAGGGAGGAGGTTTTACTGTTTGTGTGTGGCTTGGTCAGGAGACTGCAGTGGGCTGAATGAGA

AACTAAGCTCGGACTTTTAAGAAGTGGTGAGGCTTGGCCTGCAGCAGTTCTGTGTGTTGTCTCTG

TGGCATTTACTTCTCGGATCGTACCTTCAAAGGCTGGGGAGAATCAGAATTATACAGGGAGGGAG

AGACTGAGTGTGAGTGAGTGTGCGTGGCAGTGGTGTTTCTTAGGACGATGGGTTCTGGGGGGTCA

TAATCTGCTTCGAGGAGGTTTTCATTTCTGGCTGAACAAGGCTGTGGTAAGGCAAGTCCGGAAGG

CATGCTGGAAACTTGAGGGAAGTTTTGAATGGAAACTGCAGTCAACAGCTCCATATGATCCGCAT

GTGGCTTCCCCAGAGGCAAGTTTTCAGCTGCGTGGTGGCCTCTCCCAGTCACTCCACAGGCTGCC

CTGACGCTATTAATATTTGCTGAAGCAAGACCTGAGGTTCGTTGCAGATGGATTACACAATGTAT

TCCAAAACCAAATGTTACTGTTTTCCTGTATTCTCCATCCTTTCAAATTGGCCAGGCTAACATAG

ACCTCCACTGAGAGAATTTCAGAATCATTTGGTAGTTGAGAAGCGCCTACTTCATGCGGAGGCCC

CGTGGGAGGAGTGGAAGAGTTGGCCTCAGCACTGGCGAGTATCGGATGGGAGCTCTGCTCACTTG

GTAAGTCCTTCTGCTAGAACCAAGGGAGGCTGTTCAGATCCATCACAAAGAAGTTGTCGGTCACA

TCCAGGTTGTCTTCTGAGTTTGAGGTGGGATGGAGGTGGCTGCTGAGAATCCATGTGGGTCAAGA

GCTCCAAAGCTTCACTTTTACTTCGCACTCTGTCCCGGGGCATGGACGTCCTCAATGGAGGTCAT

GCAAGCCCTTCCCCCTCACCCCTTCTCTTGGCCCTCTTCATTGTCTCTACATACCCTTGGGTCAA

GAGTGTAGTGGTTCTCCCTTGTCACCCTGGAAGAGAAGCTCTTAGTTTTATTTGCTGGGTCTCCT

AGACTGAAATGATAAAGCTGAAATGATAAAAGGCGTATCATGGCTTTAGAACCCTTCTTATTTCC

CTCGCTCGCACCCCCTAGTTTTCCTTCTCTTCCCTTGAAAATCAGTGAAAATCAGGCCACATCTC

TGATGATGGCCTTTTGTTTCTTTTTCTTTTTCTGTTTCTGCCTTCGTTAGGTAAGCACAAATTTG

ATGTCCCAAGAGGCAGGCCGGTGACCCTTCAGGCCAAGTGCCTGGATGTGGCAAAGCTACAATAA

ATATCGAATGGTGAGAGCAATGGAAATTTAGCAAAGCCATAACCGGGGAGACCTCAGAGGGGCAG

TGGACTGGTTAAGAGGCTGTTGGATGAGCCGGGTAGTATTTCTACTTCAACCTGATTGAAATGTC

GACTAAAAATCAATGCTGTTGACTAGTGATAATTTACAACGTTCCTGGTGCTAAGTAGTTCCCCG

CTTAAGAATGCGTTGGCTGGGCAGAGATTAGCGCAGGGAGTTGTGTGTGTCACAATGAATCAGAC

GCATTATAGGTCAGCCCTTTATTTGTTTCATCATGACTTTTACACAGTTGTCATGTAATTTATGG

CTGCTTTCACGTTGTCAAACATTTTCATTGCATCTTCTTCTTTAACACCCTCCTGACATAGACAC

ACTGCACTTGAAGGCTTGGTATTGTTTCATAATCCGAGAGGAGGCCTATAAACCATCAAATTACA

CTATCTTTGGGCTAATCTAAATGCGCTGCAGATTAAAATCAGAGCTCATTTGTCCCTGATGCAAA

TTATTAAGTTCTAATTATAAATACCCATTTAATTACCCGACACATTTTTATTTTGCGGACCCTTT

TGAGCACTGCTGTCTGCGATGCAGAGGGGGTGGGGGGAGATGCATAGGAGACAATCTGCAGTAAT

TAATGTACACTTCCCAAATGGTAAAGGATAAACATATGCTGCTTTGTTTGTCTTATTTATTTATT

GATTAGATGTATAGAGACTTTGGCGTGGGCACAATCTGAAGTTGAAATCCTTTTAAAGATGAAAA

CTATTTAAAAATCTTTTGGGGAAGAAAGAGCAAAATATAGCCAACCAATAGCTTTCTGCTAGAAC

ACATCATCCCAAAATATGGGATTCTGAATTTGATCAAATCACCAGTTTCTGAATTTGATCAAATC

TAGATTTTGCAGAAGTTCAGGGTGAGAGAAACCATGCCTGTTTTATATCTAGAAAGTGAAATCAT

TGTTATAGAAAAAACCTACTGTGGTTAGAAAAAAACCACATTCTTTTTTCCCAGCCCTGCTGCCA

TCCTCTACCAGAAAATAACAGTATCTGCCTGTAGTATGAAGACCTTCCAATTGAGAGCATTATGA

TAAACTATTTTTGATTACCAAACACGAATGAAGGAAGAAGATAACATAAAAATTAGTAAAGGCCT

TCCAAGTAGACATTTACCCTTCTGTGAAAGCCATGGAGAAATTACCAAGACTGGTTTGGGGGGAG

GGCATTTAAGGTCTTTTGGGCATTACAGATTTTCCAGAACCAAACTTTGACTTTTAGTGTTAACA

GAGAGACACTGATCTGAAAACCAGGACACCTGGGTTCTGACCCTTATTGTATCATGCTGTGAGAT

TTTGGGCTCCCTTCACCTGTTAGCATTTGTTTCCTTGTCTTGTAAAGTAGGTAAAATAGATAGTT

TGGACTGGGTGGGTCTCTAAGTCCCCATGATGTTCTAGCATAGTATGAACACCACTGACCAGTTT

TCTCCCTGCTATTTTTTGGAATCTAGTTGCTGAATGGGGCTCACCTGCAAAGACAGCAGAATATT

ATTTTCTTGATTTGCCTCAAAGATGGAAGCTATGGTGGAGATTAAGGCTTGGATTCGTGATTCCC

CAACAGAAAGCTTAAAGGCATCTTTCAAATTGCTGGAAGCAAAATTGAAGTGCAGTATAATGGAA

TGGTGATAATTCACAGAAGTTTCCAGCCTTATAAGATTTCTCCATCTTTTAATTGTTGCAAGCTG

TTTTTTTTGAAAAACTCCAAAGAATGTAATGTGTATTTTCTCCAAGTTTGCTTTTTTGGGCAAAT

GTAACTACATCAAAATAGAAGTACGTTTTTGAAAAAGAAATAGTTGAATTCAAACAACCAGGTAT

TTTAAATTCAATTAACTGACTGAATTCAGTGATATTTTCCTCCTTCCTCCTCCCAAAAGCTGGTT

TCTCTGTATGGACATAGCCTACATATGCTGAGTCCCTGGAGTTAGGAATTTTTGCTTGTTAAAGG

CATCCGATGCAACATGTTTAGAAGAACTCTCCCTCTGTTAGTGTTGAAGACAGCATAAATTGAGG

GAAAATGTTCTTTTTTTATTCATCATGTAGGTAAAAGCATATGGCCTGTTCTGGGACATGCGATC

TTTGCAATCCATTTTTTAAACTTGGTGTTTACCATTGGCTTTTAGCACGGATGTTTCTGTTTTCC

ACACTGTCCAGCAAATACCATTTATATGTGGCATTGAATGAGATATGAAATGTTTTCAGAAGCAT

GCTGAAAAAGGGCATTCAAAGTTATCCTTTGGATAATGATGATCTAAAACTTTCTTTTATTATCC

CATGTGCTCAGAGTAAGGGGCAAATGAATCAGTTGTGAAATATGTGTTCCTTGTAGGACACAGGC

ACTCTTGAGATCTATAGCTTCAATAAAAAGGTAATTTATTTAAATTACTGCCTCTTTAATTTATA

ATGTTTTGGGGATTTTTAATAGGCATGCTCTGTAAGGGCACTGGTAATCAGCTGTTTCTGATTTT

GCATGCTCTTCTATCTCTGGTAACAAAATAAAATCTTAAAAAACAAGAAAAAAGAAAAAAAAACA

AAAACAAAAACAAGGAACATAAAGTTTAGCCCTAACCCAACCCAAAAGCAAATAACAGGCCGAAT

GAATGGCAGCCCCCCAGAGGCTCTACTTTCCCCTTCCATTATTACCTGAAATAAAAGCATGATAA

CATTCATGCCAGAGATAGGTGACAAAATTATGTATTCAGACATGAAGTTTAGGATTTCATAGCCC

AATGTTCTCTCTTCTCCCCCACCTCTTATTGTGTTGTGCAAATGTATCAGCCGTTGTATTGTTAA

TGCATGATAGGAAGCTGCCGCTAGGACAGTCTTGGCTCACTAATGCGGTCAGCTGTGTCACAATG

TGATATATAGATTATATTTACCATGGCATATTTTGTTTGCGAAATGGGAGCGGATGATAAATGAA

GATACCCTCCAGTTTTCACACTAGITCCTGTGGTCCGGAGTCTCTCAAACAATAAAGCACCCCTG

ATAATGGAGAGGTATTTATGGGAACATAATTGACTTCAAAGTTTTAGATCTCTGGCTGAAGTTTA

AGATGGGATAGTCCATTACATTAATGTCTGTGCTTAAAGCTCCTATTTGGCTTAAATAAATTATT

TAGGGTTTACTGCTTAAACCTTGGTCAATTCTTGAACGTTTGGGCTAGTTAAGTAATTTTCCAGT

GACTTTCTGTGCCTTGGTGATTCATTTACTTGATTGAGCTCCTGTGTGCTCGTATGATTTCTAAA

TGTATTTCTCAAGTTTTGCCTGGCAATGAATGATTTTGCTTACTGGAGTCTTGTGTGGTACACCT

ATAAAAGGCTTATTAACTCTTTTTGAAAAAAAAAAAAATCCCCAAACACATCAACACTGTCATCA

TAAGATAAAGCATATATACATATGCATCTATATACACACATACATATGTACATACTACATATATA

CATACGTATATGCATGTATGAATATATATATAGTTGTGTGCCTGTGTGTGTGTAGAAAGGGAGAG

AGAGAGAATAGGAAAGTCTTTAGAATTCACCATGATTCCATCAAATCAATATAGAAGTTTTTGAA

AGCTATCCATGTAGAAACCACTTTTCATCAAAATCTGACTTAAGCAAATTATCTCCATACTATTT

ATCTGAAAGTCTGTTGTTCACATAGCGCTGGATTGAGGATCATAGTGGCAAATTTAGGAGCAACA

GTCCCAAGCAGGAATCCTGGATGGCAGGCTGTCCTTTGTGCCTCCCCTGAGTTGAGAAGACTGGT

GTTTATTCTTTCTCTAGGTTGCAACACGTGTTGCCTTGAAATCTCCCTTCTTTACGGTTCTGCCA

TGAGTGTATTTTCTGTGACCTGCCTCTGCATCTGGTTAAATGGACTTCAGTAATCTGTACACAGT

TACTTCTTACTTATTTTATATCCTGAAAGATATTAAGTCCAACAAGCTTTTACCCACAGAGTCTA

CAGAGAAAACGGCCAGGCAATTTTTGTTTCAATCTCTGTGTCTCTCTGGAGCACTAGTTCCAGAG

GCTGATCAATAGGTTTTATTGTAGACCTCACTGTCTCTAAAAGCATTTTGACCTTATCCTGTCTA

AAAATAGTATTTGCTCTTGCCTGCAGAACCTTGACCTGTGAAAACCCATTTGGAACATAACTGAC

ATATCTAGTCAGCTGTATATCCAAGACATGCTCTGTGAATGAATTCTGTGCAGAACCGTCCAGGA

GAACACTTTCTTCCAAGACAAATGAATTCCAGTTCTGAACACTGGGAGTGCACCTGCTTGTCGGA

TGTGGTGATGGGCCACATGGTGGGGAGTGAGGGAGACTCAGGGCCTGTGGGGCAGTCGATGTGGG

AGGACTGTCACAGAGACTCTCAGAGGGTGCATTCAGCCCTGAACAGGGCAAAGGACTGCAAGGGG

CAGGAGCTTGGGCTGACATGCAAGGTGGCTTTACACAAGGCCCTTTTTAGAGAGTGTGATTCTCT

GAAGCTTTTCTTGGCAGCTTCAGTCTTGAACCTCACTGGAAGGGATCCTCCAAAACATGACCCAG

ATGGAAAGAAGTATTTCTGAGTTTAAAATAACTCCCCTATTTGGTAATACGGGACTTTATTTGTG

ACTTTATTATTTTTAGGTGTGATAATGGTTTTGCAGTTGTATTTAAAAGAAAAAAAACGAGTTCC

TATGTTTAAAAAATACATACAGAGGTGTTTACTGATGAAATGATATGACGTCTGGGATCAACTTA

AATAATAAAATGGGCTAGGGAGGCGATAGGGTTACAGAAGACAAGAATGACTGTGAGCTGTGGTG

GTTGGAGCTGGAAGATGTGGACTTGGGGACTGATTTATAACATTCTCTCTACTTTTGTAGTATTT

GAGATTTTTCCAGAAAATAAAGGTATTGCCTGACTGGTGGAGAGCAGTATGGCCTTGTTTAGTCG

GTGTTGTTTCTTCACCAAGGGTTTGGCTCAGAGGTAGCAAGGGGACAAGTGTCCTATGGGCAAGA

AAGTACCTGTGAGCTCAAGTCTTGTATCTGGGAAGTTCATTGTGAAGGGGTCATTTAAGGGTCTG

TACTGTGCACTGTCCCCCATTCTCCTGGAAGAACAGAGATCCCTTGTCTTTTTCAGTGCATGAGG

CAGAGTCAGATGTGGCGTTTGCTTGAGTTTCAGCACAGGTGCCTCTGTGCCTCGTGGTGAGGGTC

AGGAAGAAGCAGCTGGGACGTGCTCACGTGGCTGGTAGTGTTATGAAGACAAGGCTTTGGGACCT

TTCTTTGGCCATTTGAGCCCTGGCTATTAGAGAAAGATGATTTGCCTGAGAGGAGATTGACCACA

CTCTCAGAAAGAAGGGGACAAAGAACACGTCAAGGGTTAAGCAGCCTTCCCTTTAAGGGAGGACT

GGGGCACAAGATGGAAGATGAAAGGGAGCAGAGTGGCAATTGCAGAGCTGGAAAGGGGAATTTTG

TTCTTCTAGATAGCAAAAGCCAGGACTGTCGCTGTGTGACTTGAAAGCTAGGTCACTGGTGGGCT

TCGTGCAGCCCGTCACAGGGGAGCCATGGTGGGCCTCGTCTCTGCCGTATCTGCTGCCTGGAAGC

TGAGACTGGCCTAACCACATCACACCATTCCCAGACCCAGGCCCAGGCCCAGGCCCGGGTCCCTC

TGGTTTTACAAAATGTCCGCTCTCTCTCGCTTCACACAGAGGCTATTATTAGCAAGTGTCACTCA

GTTATCTGAGAGTGGCGCTTTTAGCTGCCATCTAAGTGCCTGATACTTGGGTTTACAGCAGATTA

AATTAAATTTTAGGCTGGTTTGGCTTCACTGGCAGTAGACAATGGAAGGCAGCTGTTGTAGAAAT

GTAACCTGGCACCCTCAAGGATTTGTGTGAGTGTGTGTGTGTGTGTGTGTGTGAGTGTGTGTGTG

TGTGTGTGTGTGTGTGTGTGTGCTGACCACTAGGCTACACTTCCTTTTCCTTTCCTCTCCATTTC

ATCCCTTTCCAAAAAGTGTTTAGACAAATAGTTTCCCAGACTTGGTTTTATCATGCTGGGTTGAC

AAAGGTTGTGTACAGAGCTGGAATAATTTTTTCTTCTTTCTACTGTTGGCACATCAATATCTTTT

TTTCTGC

BCL11A-
GTCTCTGTCCATCCAGACTCCTGACGTTCAAGTTCGCAGGGACGTCACGTCCGCACTTGAACTTG

Exon 1-
CAGCTCAGGGGGGCTTTTGCCATTTTTTTCATCTCTCTCTCTCTCTCTCCCTCTATCTCTCTTCT

SEQ ID NO:
CTCTCTCTCCCTCTTTTTTTTTTTTTTTTTTTTTTTTTTTTTGCTTAAAAAAAAGCCATGACGGC

2636
TCTCCCACAATTCATCTTCCCTGCGCCATCTTTGTATTATTTCTAATTTATTTTGGATGTCAAAA

GGCACTGATGAAGATATTTTCTCTGGAGTCTCCTTCTTTCTAACCCGGCTCTCCCGATGTGAACC

GAGCCGTCGTCCGCCCGCCGCCGCCGCCGCCGCCGCCGCCGCCCGCCCCGCAGCCCACCATGTCT

CGCCGCAAGCAAGGCAAACCCCAGCACTTAAGCAAACGGGAATTCTCGCGTAAGTAACCCAATAA

TAGTAATAATAATTATTAATAATCACGAGAGCGC

BCL11A-
CTGTCCTCTCTGGCACTCTAATAATTGTGCTTTTGTTTCTCCAACCACAGCCGAGCCTCTTGAAG

Exon 2-
CCATTCTTACAGATGATGAACCAGACCACGGCCCGTTGGGAGCTCCAGAAGGGGATCATGACCTC

SEQ ID NO:
CTCACCTGTGGGCAGTGCCAGATGAACTTCCCATTGGGGGACATTCTTATTTTTATCGAGCACAA

2637
ACGGAAACAATGCAATGGCAGCCTCTGCTTAGAAAAAGCTGTGGATAAGCCACCTTCCCCTTCAC

CAATCGAGATGAAAAAAGCATCCAATCCCGTGGAGGTTGGCATCCAGGTCACGCCAGAGGATGAC

GATTGTTTATCAACGTCATCTAGAGGAATTTGCCCCAAACAGGAACACATAGCAGGTAAATGAGA

AGCAAGGAGAAAAGCTGTTTGCATGTTTTCTTTTCATTTT

BCL11A-
GATGCACGTTGTTTGTAGCTGTAGTGCTTGATTTTGGGTTTCTTTCACAGATAAACTTCTGCACT

Exon 3-
GGAGGGGCCTCTCCTCCCCTCGTTCTGCACATGGAGCTCTAATCCCCACGCCTGGGATGAGTGCA

SEQ ID NO:
GAATATGCCCCGCAGGGTATTTGTAAGTTGAGCCTTATTTCTTCTACAAATGTCCATGTGTATAG

2638
AGATGAG

BCL11A
TGCCCGCCTCAGTGATTAAACATTGATGTTGGTGTTGTATTATTTTGCAGGTAAAGATGAGCCCA

Exon 4-
GCAGCTACACATGTACAACTTGCAAACAGCCATTCACCAGTGCATGGTTTCTCTTGCAACACGCA

SEQ ID NO:
CAGAACACTCATGGATTAAGAATCTACTTAGAAAGCGAACACGGAAGTCCCCTGACCCCGCGGGT

2639
TGGTATCCCTTCAGGACTAGGTGCAGAATGTCCTTCCCAGCCACCTCTCCATGGGATTCATATTG

CAGACAATAACCCCTTTAACCTGCTAAGAATACCAGGATCAGTATCGAGAGAGGCTTCCGGCCTG

GCAGAAGGGCGCTTTCCACCCACTCCCCCCCTGTTTAGTCCACCACCGAGACATCACTTGGACCC

CCACCGCATAGAGCGCCTGGGGGCGGAAGAGATGGCCCTGGCCACCCATCACCCGAGTGCCTTTG

ACAGGGTGCTGCGGTTGAATCCAATGGCTATGGAGCCTCCCGCCATGGATTTCTCTAGGAGACTT

AGAGAGCTGGCAGGGAACACGTCTAGCCCACCGCTGTCCCCAGGCCGGCCCAGCCCTATGCAAAG

GTTACTGCAACCATTCCAGCCAGGTAGCAAGCCGCCCTTCCTGGCGACGCCCCCCCTCCCTCCTC

TGCAATCCGCCCCTCCTCCCTCCCAGCCCCCGGTCAAGTCCAAGTCATGCGAGTTCTGCGGCAAG

ACGTTCAAATTTCAGAGCAACCTGGTGGTGCACCGGCGCAGCCACACGGGCGAGAAGCCCTACAA

GTGCAACCTGTGCGACCACGCGTGCACCCAGGCCAGCAAGCTGAAGCGCCACATGAAGACGCACA

TGCACAAATCGTCCCCCATGACGGTCAAGTCCGACGACGGTCTCTCCACCGCCAGCTCCCCGGAA

CCCGGCACCAGCGACTTGGTGGGCAGCGCCAGCAGCGCGCTCAAGTCCGTGGTGGCCAAGTTCAA

GAGCGAGAACGACCCCAACCTGATCCCGGAGAACGGGGACGAGGAGGAAGAGGAGGACGACGAGG

AAGAGGAAGAAGAGGAGGAAGAGGAGGAGGAGGAGCTGACGGAGAGCGAGAGGGTGGACTACGGC

TTCGGGCTGAGCCTGGAGGCGGCGCGCCACCACGAGAACAGCTCGCGGGGCGCGGTCGTGGGCGT

GGGCGACGAGAGCCGCGCCCTGCCCGACGTCATGCAGGGCATGGTGCTCAGCTCCATGCAGCACT

TCAGCGAGGCCTTCCACCAGGTCCTGGGCGAGAAGCATAAGCGCGGCCACCTGGCCGAGGCCGAG

GGCCACAGGGACACTTGCGACGAAGACTCGGTGGCCGGCGAGTCGGACCGCATAGACGATGGCAC

TGTTAATGGCCGCGGCTGCTCCCCGGGCGAGTCGGCCTCGGGGGGCCTGTCCAAAAAGCTGCTGC

TGGGCAGCCCCAGCTCGCTGAGCCCCTTCTCTAAGCGCATCAAGCTCGAGAAGGAGTTCGACCTG

CCCCCGGCCGCGATGCCCAACACGGAGAACGTGTACTCGCAGTGGCTCGCCGGCTACGCGGCCTC

CAGGCAGCTCAAAGATCCCTTCCTTAGCTTCGGAGACTCCAGACAATCGCCTTTTGCCTCCTCGT

CGGAGCACTCCTCGGAGAACGGGAGTTTGCGCTTCTCCACACCGCCCGGGGAGCTGGACGGAGGG

ATCTCGGGGCGCAGCGGCACGGGAAGTGGAGGGAGCACGCCCCATATTAGTGGTCCGGGCCCGGG

CAGGCCCAGCTCAAAAGAGGGCAGACGCAGCGACACTTGTGAGTACTGTGGGAAAGTCTTCAAGA

ACTGTAGCAATCTCACTGTCCACAGGAGAAGCCACACGGGCGAAAGGCCTTATAAATGCGAGCTG

TGCAACTATGCCTGTGCCCAGAGTAGCAAGCTCACCAGGCACATGAAAACGCATGGCCAGGTGGG

GAAGGACGTTTACAAATGTGAAATTTGTAAGATGCCTTTTAGCGTGTACAGTACCCTGGAGAAAC

ACATGAAAAAATGGCACAGTGATCGAGTGTTGAATAATGATATAAAAACTGAATAGAGGTATATT

AATACCCCTCCCTCACTCCCACCTGACACCCCCTTTTTCACCACTCCCCTTCCCCATCGCCCTCC

AGCCCCACTCCCTGTAGGATTTTTTTCTAGTCCCATGTGATTTAAACAAACAAACAAACAAACAG

AAGTAACGAAGCTAAGAATATGAGAGTGCTTGTCACCAGCACACCTGTTTTTTTTCTTTTTCTTT

TTCTTTTTTCTTTTTCCTTTTTTTTTTTTTTCCTTTATGTTCTCACCGTTTGAATGCATGATCTG

TATGGGGCAATACTATTGCATTTTACGCAAACTTTGAGCCTTTCTCTTGTGCAATAATTTACATG

TTGTGTATGTTTTTTTTTAAACTTAGACAGCATGTATGGTATGTTATGGCTATTTTAAATTGTCC

CTAATTCGTTGCTGAGCAAACATGTTGCTGTTTCCAGTTCCGTTCTGAGAGAAAAAGAGAGAGAG

AGAGAAAAAGACCATGCTGCATACATTCTGTAATACATATCATGTACAGTTTTATTTTATAACGT

GAGGAGGAAAAACAGTCTTTGGATTAACCCTCTATAGACAGAATAGATAGCACTGAAAAAAAATC

TCTATGAGCTAAATGTCTGTCTCTAAAGGGTTAAATGTATCAATTGGAAAGGAAGAAAAAAGGCC

TTGAATTGACAAATTAACAGAAAAACAGAACAAGTTTATTCTATCATTTGGTTTTAAAATATGAG

TGCCTTGGATCTATTAAAACCACATCGATGGTTCTTTCTACTTGTTATAAACTTGTAGCTTAATT

CAGCATTGGGTGAGGTAATAAACCTTAGGAACTAGCATATAATTCTATATTGTATTTCTCACAAC

AATGGCTACCTAAAAAGATGACCCATTATGTCCTAGTTAATCATCATTTTTCCTTTAGTTTAATT

TTATAAACAAAACTGATTATACCAGTATAAAAGCTACTTTGCTCCTGGTGAGAGCTTAAAAGAAA

TGGGCTGTTTTGCCCAAAGTTTTATTTTTTTTAAACAATGATTAAATTGAATGTGTAATGTGCAA

AAGCCCTGGAACGCAATTAAATACACTAGTAAGGAGTTCATTTTATGAAGATATTTGCTTTAATA

ATGTCTTTTTAAAAATACTGGCACCAAAAGAAATAGATCCAGATCTACTTGGTTGTCAAGTGGAC

AATCAAATGATAAACTTTAAGACCTTGTATACCATATTGAAAGGAAGAGGCTGACAATAAGGTTT

GACAGAGGGGAACAGAAGAAAATAATATGATTTATTAGCACAACGTGGTACTATTTGCCATTTAA

AACTAGAACAGGTATATAAGCTAATATTGATACAATGATGATTAACTATGAATTCTTAAGACTTG

CATTTAAATGTGACATTCTTAAAAAAAGAAGAGAAAGAATTTTAAGAGTAGCAGTATATATGTCT

GTGCTCCCTAAAAGTTGTACTTCATTTCTTTTCCATACACTGTGTGCTATTTGTGTTAACATGGA

AGAGGATTCATTGTTTTTATTTTTATTTTTTTAATTTTTTCTTTTTTATTAAGCTAGCATCTGCC

CCAGTTGGTGTTCAAATAGCACTTGACTCTGCCTGTGATATCTGTATCTTTTCTCTAATCAGAGA

TACAGAGGTTGAGTATAAAATAAACCTGCTCAGATAGGACAATTAAGTGCACTGTACAATTTTCC

CAGTTTACAGGTCTATACTTAAGGGAAAAGTTGCAAGAATGCTGAAAAAAAATTGAACACAATCT

CATTGAGGAGCATTTTTTAAAAACTAAAAAAAAAAAAACTTTGCCAGCCATTTACTTGACTATTG

AGCTTACTTACTTGGACGCAACATTGCAAGCGCTGTGAATGGAAACAGAATACACTTAACATAGA

AATGAATGATTGCTTTCGCTTCTACAGTGCAAGGATTTTTTTGTACAAAACTTTTTTAAATATAA

ATGTTAAGAAAAATTTTTTTTAAAAAACACTTCATTATGTTTAGGGGGGAACTGCATTTTAGGGT

TCCATTGTCTTGGTGGTGTTACAAGACTTGTTATCCATTTAAAAATGGTAGTGGAAATTCTATGC

CTTGGATACACACCGCTCTTCAGGTTGTAAAAAAAAAAAACATACATTGGGGAAAGGTTTAAGAT

TATATAGTACTTAAATATAGGAAAATGCACACTCATGTTGATTCCTATGCTAAAATACATTTATG

GTCTTTTTTCTGTATTTCTAGAATGGTATTTGAATTAAATGTTCATCTAGTGTTAGGCACTATAG

TATTTATATTGAAGCTTGTATTTTTAACTGTTGCTTGTTCTCTTAAAAGGTATCAATGTACCTTT

TTTGGTAGTGGAAAAAAAAAAGACAGGCTGCCACAGTATATTTTTTTAATTTGGCAGGATAATAT

AGTGCAAATTATTTGTATGCTTCAAAAAAAAAAAAAAGAGAGAAACAAAAAAGTGTGACATTACA

GATGAGAAGCCATATAATGGCGGTTTGGGGGAGCCTGCTAGAATGTCACATGGATGGCTGTCATA

GGGGTTGTACATATCCTTTTTTGTTCCTTTTTCCTGCTGCCATACTGTATGCAGTACTGCAAGCT

AATAACGTTGGTTTGTTATGTAGTGTGCTTTTTGTCCCTTTCCTTCTATCACCCTACATTCCAGC

ATCTTACCTTCATATGCAGTAAAAGAAAGAAAGAAAAAAAAAGGAAAAAAAAAAAAAAACCAATG

TTTTGCAGTTTTTTTCATTGCCAAAAACTAAATGGTGCTTTATATTTAGATTGGAAAGAATTTCA

TATGCAAAGCATATTAAAGAGAAAGCCCGCTTTAGTCAATACTTTTTTGTAAATGGCAATGCAGA

ATATTTTGTTATTGGCCTTTTCTATTCCTGTAATGAAAGCTGTTTGTCGTAACTTGAAATTTTAT

CTTTTACTATGGGAGTCACTATTTATTATTGCTTATGTGCCCTGTTCAAAACAGAGGCACTTAAT

TTGATCTTTTATTTTTCTTTGTTTTTATTTTTTTTTTTATTTAGATGACCAAAGGTCATTACAAC

CTGGCTTTTTATTGTATTTGTTTCTGGTCTTTGTTAAGTTCTATTGGAAAAACCACTGTCTGTGT

TTTTTTGGCAGTTGTCTGCATTAACCTGTTCATACACCCATTTTGTCCCTTTATTGAAAAAATAA

AAAAAATTAAAGTACACATTGTAAGCTTCTTGTGTCCTCATTTGACACACTCTGTAAATTACTTG

C

BCL11A-
CATCTACTCTTAGACATAACACACCAGGGTCAATACAACTTTGAAGCTAGTCTAGTGCAAGCTAA

Enhancer
CAGTTGCTTTTATCACAGGCTCCAGGAAGGGTTTGGCCTCTGATTAGGGTGGGGGCGTGGGTGGG

region-
GTAGAAGAGGACTGGCAGA

SEQ ID NO:

2640

SEQ ID NO:
MSSAIKSYKS VLRPNERKNQ LLKSTIQCLE DGSAFFFKML QGLEGGITPE IVRFSTEQEK

2641
QQQDIALWCA VNWFRPVSQD SLTHTIASDN LVEKFEEYYG GTASDAIKQY FSASIGESYY

(Variant
WNDCRQQYYD LCRELGVEVS DLTHDLEILC REKCLAVATE SNQNNSIISV LFGTGEKEDR

Cas12i2 of
SVKLRITKKI LEAISNLKEI PKNVAPIQEI ILNVAKATKE TFRQVYAGNL GAPSTLEKFI

SEQ ID NO: 3
AKDGQKEFDL KKLQTDLKKV IRGKSKERDW CCQEELRSYV EQNTIQYDLW AWGEMENKAH

of
TALKIKSTRN YNFAKQRLEQ FKEIQSLNNL LVVKKLNDFF DSEFFSGEET YTICVHHLGG

PCT/US2021/
KDLSKLYKAW EDDPADPENA IVVLCDDLKN NFKKEPIRNI LRYIFTIRQE CSAQDILAAA

025257)
KYNQQLDRYK SQKANPSVLG NQGETWTNAV ILPEKAQRND RPNSLDLRIW LYLKLRHPDG

RWKKHHIPFY DTRFFQEIYA AGNSPVDTCQ FRTPRFGYHL PKLTDQTAIR VNKKHVKAAK

TEARIRLAIQ QGTLPVSNLK ITEISATINS KGQVRIPVKF RVGRQKGTLQ IGDRFCGYDQ

NQTASHAYSL WEVVKEGQYH KELGCFVRFI SSGDIVSITE NRGNQFDQLS YEGLAYPQYA

DWRKKASKFV SLWQITKKNK KKEIVTVEAK EKFDAICKYQ PRLYKENKEY AYLLRDIVRG

KSLVELQQIR QEIFRFIEQD CGVTRLGSLS LSTLETVKAV KGIIYSYFST ALNASKNNPI

SDEQRKEFDP ELFALLEKLE LIRTRKKKQK VERIANSLIQ TCLENNIKFI RGEGDLSTIN

NATKKKANSR SMDWLARGVF NKIRQLAPMH NITLFGCGSL YTSHQDPLVH RNPDKAMKCR

WAAIPVKDIG RWVLRKLSQN LRAKNRGTGE YYHQGVKEFL SHYELQDLEE ELLKWRSDRK

SNIPCWVLQN RLAEKLGNKE AVVYIPVRGG RIYFATHKVA TGAVSIVEDQ KQVWVCNADH

VAAANIALTG KGIGEQSSDE ENPDGSRIKL QLTS

SEQ ID NO:
MSSAIKSYKS VLRPNERKNQ LLKSTIQCLE DGSAFFFKML QGLEGGITPE IVRESTEQEK

2642
QQQDIALWCA VNWFRPVSQD SLTHTIASDN LVEKFEEYYG GTASDAIKQY FSASIGESYY

(Variant
WNDCRQQYYD LCRELGVEVS DLTHDLEILC REKCLAVATE SNQNNSIISV LFGTGEKEDR

Cas12i2 of
SVKLRITKKI LEAISNLKEI PKNVAPIQEI ILNVAKATKE TFRQVYAGNL GAPSTLEKFI

SEQ ID NO: 4
AKDGQKEFDL KKLQTDLKKV IRGKSKERDW CCQEELRSYV EQNTIQYDLW AWGEMENKAH

of
TALKIKSTRN YNFAKQRLEQ FKEIQSLNNL LVVKKLNDFF DSEFFSGEET YTICVHHLGG

PCT/US2021/
KDLSKLYKAW EDDPADPENA IVVLCDDLKN NFKKEPIRNI LRYIFTIRQE CSAQDILAAA

025257)
KYNQQLDRYK SQKANPSVLG NQGFTWTNAV ILPEKAQRND RPNSLDLRIW LYLKLRHPDG

RWKKHHIPFY DTRFFQEIYA AGNSPVDTCQ FRTPRFGYHL PKLTDQTAIR VNKKHVKAAK

TEARIRLAIQ QGTLPVSNLK ITEISATINS KGQVRIPVKF RVGRQKGTLQ IGDRFCGYDQ

NQTASHAYSL WEVVKEGQYH KELGCFVRFI SSGDIVSITE NRGNQFDQLS YEGLAYPQYA

DWRKKASKFV SLWQITKKNK KKEIVTVEAK EKFDAICKYQ PRLYKENKEY AYLLRDIVRG

KSLVELQQIR QEIFRFIEQD CGVTRLGSLS LSTLETVKAV KGIIYSYFST ALNASKNNPI

SDEQRKEFDP ELFALLEKLE LIRTRKKKQK VERIANSLIQ TCLENNIKFI RGEGDLSTTN

NATKKKANSR SMDWLARGVF NKIRQLAPMH NITLFGCGSL YTSHQDPLVH RNPDKAMKCR

WAAIPVKDIG DWVLRKLSQN LRAKNRGTGE YYHQGVKEFL SHYELQDLEE ELLKWRSDRK

SNIPCWVLQN RLAEKLGNKE AVVYIPVRGG RIYFATHKVA TGAVSIVEDQ KQVWVCNADH

VAAANIALTG KGIGEQSSDE ENPDGSRIKL QLTS

SEQ ID NO:
MSSAIKSYKS VLRPNERKNQ LLKSTIQCLE DGSAFFFKML QGLEGGITPE IVRESTEQEK

2643
QQQDIALWCA VNWFRPVSQD SLTHTIASDN LVEKFEEYYG GTASDAIKQY FSASIGESYY

(Variant
WNDCRQQYYD LCRELGVEVS DLTHDLEILC REKCLAVATE SNQNNSIISV LFGTGEKEDR

Cas12i2 of
SVKLRITKKI LEAISNLKEI PKNVAPIQEI ILNVAKATKE TFRQVYAGNL GAPSTLEKFI

SEQ ID NO: 5
AKDGQKEFDL KKLQTDLKKV IRGKSKERDW CCQEELRSYV EQNTIQYDLW AWGEMENKAH

of
TALKIKSTRN YNFAKQRLEQ FKEIQSLNNL LVVKKLNDFF DSEFFSGEET YTICVHHLGG

PCT/US2021/
KDLSKLYKAW EDDPADPENA IVVLCDDLKN NFKKEPIRNI LRYIFTIRQE CSAQDILAAA

025257)
KYNQQLDRYK SQKANPSVLG NQGFTWTNAV ILPEKAQRND RPNSLDLRIW LYLKLRHPDG

RWKKHHIPFY DTRFFQEIYA AGNSPVDTCQ FRTPRFGYHL PKLTDQTAIR VNKKHVKAAK

TEARIRLAIQ QGTLPVSNLK ITEISATINS KGQVRIPVKF RVGRQKGTLQ IGDRFCGYDQ

NQTASHAYSL WEVVKEGQYH KELGCFVRFI SSGDIVSITE NRGNQFDQLS YEGLAYPQYA

DWRKKASKFV SLWQITKKNK KKEIVTVEAK EKFDAICKYQ PRLYKENKEY AYLLRDIVRG

KSLVELQQIR QEIFRFIEQD CGVTRLGSLS LSTLETVKAV KGIIYSYFST ALNASKNNPI

SDEQRKEFDP ELFALLEKLE LIRTRKKKQK VERIANSLIQ TCLENNIKFI RGEGDLSTIN

NATKKKANSR SMDWLARGVF NKIRQLAPMH NITLFGCGSL YTSHQDPLVH RNPDKAMKCR

WAAIPVKDIG DWVLRKLSQN LRAKNRGTGE YYHQGVKEFL SHYELQDLEE ELLKWRSDRK

SNIPCWVLQN RLAEKLGNKE AVVYIPVRGG RIYFATHKVA TGAVSIVEDQ KQVWVCNADH

VAAANIALTG KGIGEQSSDE ENPDGGRIKL QLTS

SEQ ID NO:
MSSAIKSYKS VLRPNERKNQ LLKSTIQCLE DGSAFFFKML QGLFGGITPE IVRESTEQEK

2644
QQQDIALWCA VNWFRPVSQD SLTHTIASDN LVEKFEEYYG GTASDAIKQY FSASIGESYY

(Variant
WNDCRQQYYD LCRELGVEVS DLTHDLEILC REKCLAVATE SNQNNSIISV LFGTGEKEDR

Cas12i2 of
SVKLRITKKI LEAISNLKEI PKNVAPIQEI ILNVAKATKE TFRQVYAGNL GAPSTLEKFI

SEQ ID NO:
AKDGQKEFDL KKLQTDLKKV IRGKSKERDW CCQEELRSYV EQNTIQYDLW AWGEMENKAH

495 of
TALKIKSTRN YNFAKQRLEQ FKEIQSLNNL LVVKKLNDFF DSEFFSGEET YTICVHHLGG

PCT/US2021/
KDLSKLYKAW EDDPADPENA IVVLCDDLKN NFKKEPIRNI LRYIFTIRQE CSAQDILAAA

025257)
KYNQQLDRYK SQKANPSVLG NQGFTWTNAV ILPEKAQRND RPNSLDLRIW LYLKLRHPDG

RWKKHHIPFY DTRFFQEIYA AGNSPVDTCQ FRTPRFGYHL PKLTDQTAIR VNKKHVKAAK

TEARIRLAIQ QGTLPVSNLK ITEISATINS KGQVRIPVKF RVGRQKGTLQ IGDRFCGYDQ

NQTASHAYSL WEVVKEGQYH KELRCRVRFI SSGDIVSITE NRGNQFDQLS YEGLAYPQYA

DWRKKASKFV SLWQITKKNK KKEIVTVEAK EKFDAICKYQ PRLYKENKEY AYLLRDIVRG

KSLVELQQIR QEIFRFIEQD CGVTRLGSLS LSTLETVKAV KGIIYSYFST ALNASKNNPI

SDEQRKEFDP ELFALLEKLE LIRTRKKKQK VERIANSLIQ TCLENNIKFI RGEGDLSTIN

NATKKKANSR SMDWLARGVF NKIRQLAPMH NITLFGCGSL YTSHQDPLVH RNPDKAMKCR

WAAIPVKDIG DWVLRKLSQN LRAKNRGIGE YYHQGVKEFL SHYELQDLEE ELLKWRSDRK

SNIPCWVLQN RLAEKLGNKE AVVYIPVRGG RIYFATHKVA TGAVSIVEDQ KQVWVCNADH

VAAANIALTG KGIGRQSSDE ENPDGGRIKL QLTS

SEQ ID NO:
MSSAIKSYKS VLRPNERKNQ LLKSTIQCLE DGSAFFFKML QGLFGGITPE IVRESTEQEK

2645
QQQDIALWCA VNWFRPVSQD SLTHTIASDN LVEKFEEYYG GTASDAIKQY FSASIGESYY

(Variant
WNDCRQQYYD LCRELGVEVS DLTHDLEILC REKCLAVATE SNQNNSIISV LFGTGEKEDR

Cas12i2 of
SVKLRITKKI LEAISNLKEI PKNVAPIQEI ILNVAKATKE TFRQVYAGNL GAPSTLEKFI

SEQ ID NO:
AKDGQKEFDL KKLQTDLKKV IRGKSKERDW CCQEELRSYV EQNTIQYDLW AWGEMENKAH

496 of
TALKIKSTRN YNFAKQRLEQ FKEIQSLNNL LVVKKLNDFF DSEFFSGEET YTICVHHLGG

PCT/US2021/
KDLSKLYKAW EDDPADPENA IVVLCDDLKN NFKKEPIRNI LRYIFTIRQE CSAQDILAAA

025257)
KYNQQLDRYK SQKANPSVLG NQGFTWTNAV ILPEKAQRND RPNSLDLRIW LYLKLRHPDG

RWKKHHIPFY DTRFFQEIYA AGNSPVDTCQ FRTPRFGYHL PKLTDQTAIR VNKKHVKAAK

TEARIRLAIQ QGTLPVSNLK ITEISATINS KGQVRIPVKF RVGRQKGTLQ IGDRFCGYDQ

NQTASHAYSL WEVVKEGQYH KELRCRVRFI SSGDIVSITE NRGNQFDQLS YEGLAYPQYA

DWRKKASKFV SLWQITKKNK KKEIVTVEAK EKFDAICKYQ PRLYKENKEY AYLLRDIVRG

KSLVELQQIR QEIFRFIEQD CGVTRLGSLS LSTLETVKAV KGIIYSYFST ALNASKNNPI

SDEQRKEFDP ELFALLEKLE LIRTRKKKQK VERIANSLIQ TCLENNIKFI RGEGDLSTIN

NATKKKANSR SMDWLARGVF NKIRQLATMH NITLFGCGSL YTSHQDPLVH RNPDKAMKCR

WAAIPVKDIG DWVLRKLSQN LRAKNRGTGE YYHQGVKEFL SHYELQDLEE ELLKWRSDRK

SNIPCWVLQN RLAEKLGNKE AVVYIPVRGG RIYFATHKVA TGAVSIVEDQ KQVWVCNADH

VAAANIALTG KGIGRQSSDE ENPDGGRIKL QLTS

SEQ ID NO:
ATGGCTTCCATCTCTAGGCCATACGGCACCAAGCTGCGACCGGACGCACGGAAGAAGGAGATGCT

2646
CGATAAGTTCTTTAATACACTGACTAAGGGTCAGCGCGTGTTCGCAGACCTGGCCCTGTGCATCT

(Nucleotide
ATGGCTCCCTGACCCTGGAGATGGCCAAGTCTCTGGAGCCAGAAAGTGATTCAGAACTGGTGTGC

sequence
ACAGCCCCAGCTCCGACAAGTACGTGTGGATCGATTGCAGGCAGAAATTCCTGAGGTTTCAGCGC

encoding
GCTATTGGGTGGTTTCGGCTGGTGGACAAGACCATCTGGTCCAAGGATGGCATCAAGCAGGAGAA

Cas12i4)
TCTGGTGAAACAGTACGAAGCCTATTCCGGAAAGGAGGCTTCTGAAGTGGTCAAAACATACCTGA

GAGCTCGGCACTCGCAACCTGTCCGAGGACTTCGAATGTATGCTCTTTGAACAGTACATTAGACT

GACCAAGGGCGAGATCGAAGGGTATGCCGCTATTTCAAATATGTTCGGAAACGGCGAGAAGGAAG

ACCGGAGCAAGAAAAGAATGTACGCTACACGGATGAAAGATTGGCTGGAGGCAAACGAAAATATC

ACTTGGGAGCAGTATAGAGAGGCCCTGAAGAACCAGCTGAATGCTAAAAACCTGGAGCAGGTTGT

GGCCAATTACAAGGGGAACGCTGGCGGGGCAGACCCCTTCTTTAAGTATAGCTTCTCCAAAGAGG

GAATGGTGAGCAAGAAAGAACATGCACAGCAGCTCGACAAGTTCAAAACCGTCCTGAAGAACAAA

GCCCGGGACCTGAATTTTCCAAACAAGGAGAAGCTGAAGCAGTACCTGGAGGCCGAAATCGGCAT

TCCGGTCGACGCTAACGTGTACTCCCAGATGTTCTCTAACGGGGTGAGTGAGGTCCAGCCTAAGA

CCACACGGAATATGTCTTTTAGTAACGAGAAACTGGATCTGCTCACTGAACTGAAGGACCTGAAC

AAGGGCGATGGGTTCGAGTACGCCAGAGAAGTGCTGAACGGGTTCTTTGACTCCGAGCTCCACAC

TACCGAGGATAAGTTTAATATCACCTCTAGGTACCTGGGAGGCGACAAATCAAACCGCCTGAGCA

AACTCTATAAGATCTGGAAGAAAGAGGGTGTGGACTGCGAGGAAGGCATTCAGCAGTTCTGTGAA

GCCGTCAAAGATAAGATGGGCCAGATCCCCATTCGAAATGTGCTGAAGTACCTGTGGCAGTTCCG

GGAGACAGTCAGTGCCGAGGATTTTGAAGCAGCCGCTAAGGCTAACCATCTGGAGGAAAAGATCA

GCCGGGTGAAAGCCCACCCAATCGTGATTAGCAATAGGTACTGGGCTTTTGGGACTTCCGCACTG

GTGGGAAACATTATGCCCGCAGACAAGAGGCATCAGGGAGAGTATGCCGGTCAGAATTTCAAAAT

GTGGCTGGAGGCTGAACTGCACTACGATGGCAAGAAAGCAAAGCACCATCTGCCTTTTTATAACG

CCCGCTTCTTTGAGGAAGTGTACTGCTATCACCCCTCTGTCGCCGAGATCACTCCTTTCAAAACC

AAGCAGTTTGGCTGTGAAATCGGGAAGGACATTCCAGATTACGTGAGCGTCGCTCTGAAGGACAA

TCCGTATAAGAAAGCAACCAAACGAATCCTGCGTGCAATCTACAATCCCGTCGCCAACACAACTG

GCGTTGATAAGACCACAAACTGCAGCTTCATGATCAAACGCGAGAATGACGAATATAAGCTGGTC

ATCAACCGAAAAATTTCCGTGGATCGGCCTAAGAGAATCGAAGTGGGCAGGACAATTATGGGGTA

CGACCGCAATCAGACAGCTAGCGATACTTATTGGATTGGCCGGCTGGTGCCACCTGGAACCCGGG

GCGCATACCGCATCGGAGAGTGGAGCGTCCAGTATATTAAGTCCGGGCCTGTCCTGTCTAGTACT

CAGGGAGTTAACAATTCCACTACCGACCAGCTGGTGTACAACGGCATGCCATCAAGCTCCGAGCG

GTTCAAGGCCTGGAAGAAAGCCAGAATGGCTTTTATCCGAAAACTCATTCGTCAGCTGAATGACG

AGGGACTGGAATCTAAGGGTCAGGATTATATCCCCGAGAACCCTTCTAGTTTCGATGTGCGGGGC

GAAACCCTGTACGTCTTTAACAGTAATTATCTGAAGGCCCTGGTGAGCAAACACAGAAAGGCCAA

GAAACCTGTTGAGGGGATCCTGGACGAGATTGAAGCCTGGACATCTAAAGACAAGGATTCATGCA

GCCTGATGCGGCTGAGCAGCCTGAGCGATGCTTCCATGCAGGGAATCGCCAGCCTGAAGAGTCTG

ATTAACAGCTACTTCAACAAGAATGGCTGTAAAACCATCGAGGACAAAGAAAAGTTTAATCCCGT

GCTGTATGCCAAGCTGGTTGAGGTGGAACAGCGGAGAACAAACAAGCGGTCTGAGAAAGTGGGAA

GAATCGCAGGTAGTCTGGAGCAGCTGGCCCTGCTGAACGGGGTTGAGGTGGTCATCGGCGAAGCT

GACCTGGGGGAGGTCGAAAAAGGAAAGAGTAAGAAACAGAATTCACGGAACATGGATTGGTGCGC

AAAGCAGGTGGCACAGCGGCTGGAGTACAAACTGGCCTTCCATGGAATCGGTTACTTTGGAGTGA

ACCCCATGTATACCAGCCACCAGGACCCTTTCGAACATAGGCGCGTGGCTGATCACATCGTCATG

CGAGCACGTTTTGAGGAAGTCAACGTGGAGAACATTGCCGAATGGCACGTGCGAAATTTCTCAAA

CTACCTGCGTGCAGACAGCGGCACTGGGCTGTACTATAAGCAGGCCACCATGGACTTCCTGAAAC

ATTACGGTCTGGAGGAACACGCTGAGGGCCTGGAAAATAAGAAAATCAAGTTCTATGACTTTAGA

AAGATCCTGGAGGATAAAAACCTGACAAGCGTGATCATTCCAAAGAGGGGGGGGCGCATCTACAT

GGCCACCAACCCAGTGACATCCGACTCTACCCCGATTACATACGCCGGCAAGACTTATAATAGGT

GTAACGCTGATGAGGTGGCAGCCGCTAATATCGTTATTTCTGTGCTGGCTCCCCGCAGTAAGAAA

AACGAGGAACAGGACGATATCCCTCTGATTACCAAGAAAGCCGAGAGTAAGTCACCACCGAAAGA

CCGGAAGAGATCAAAAACAAGCCAGCTGCCTCAGAAA

SEQ ID NO:
MASISRPYGTKLRPDARKKEMLDKFFNTLTKGQRVFADLALCIYGSLTLEMAKSLEPESDSELVC

2647
AIGWFRLVDKTIWSKDGIKQENLVKQYEAYSGKEASEVVKTYLNSPSSDKYVWIDCRQKFLRFQR

Cas12i4 amino
ELGTRNLSEDFECMLFEQYIRLTKGEIEGYAAISNMFGNGEKEDRSKKRMYATRMKDWLEANENI

acid sequence
TWEQYREALKNQLNAKNLEQVVANYKGNAGGADPFFKYSFSKEGMVSKKEHAQQLDKFKTVLKNK

of SEQ ID
ARDLNFPNKEKLKQYLEAEIGIPVDANVYSQMFSNGVSEVQPKTTRNMSFSNEKLDLLTELKDLN

NO: 14 of
KGDGFEYAREVLNGFFDSELHTTEDKFNITSRYLGGDKSNRLSKLYKIWKKEGVDCEEGIQQFCE

U.S. Pat. No.
AVKDKMGQIPIRNVLKYLWQFRETVSAEDFEAAAKANHLEEKISRVKAHPIVISNRYWAFGTSAL

10,808,245)
VGNIMPADKRHQGEYAGQNFKMWLEAELHYDGKKAKHHLPFYNARFFEEVYCYHPSVAEITPFKT

KQFGCEIGKDIPDYVSVALKDNPYKKATKRILRAIYNPVANTTGVDKTTNCSFMIKRENDEYKLV

INRKISVDRPKRIEVGRTIMGYDRNQTASDTYWIGRLVPPGTRGAYRIGEWSVQYIKSGPVLSST

QGVNNSTTDQLVYNGMPSSSERFKAWKKARMAFIRKLIRQLNDEGLESKGQDYIPENPSSFDVRG

ETLYVENSNYLKALVSKHRKAKKPVEGILDEIEAWTSKDKDSCSLMRLSSLSDASMQGIASLKSL

INSYFNKNGCKTIEDKEKFNPVLYAKLVEVEQRRTNKRSEKVGRIAGSLEQLALLNGVEVVIGEA

DLGEVEKGKSKKQNSRNMDWCAKQVAQRLEYKLAFHGIGYFGVNPMYTSHQDPFEHRRVADHIVM

RARFEEVNVENIAEWHVRNFSNYLRADSGTGLYYKQATMDFLKHYGLEEHAEGLENKKIKFYDER

KILEDKNLTSVIIPKRGGRIYMATNPVTSDSTPITYAGKTYNRCNADEVAAANIVISVLAPRSKK

NEEQDDIPLITKKAESKSPPKDRKRSKTSQLPQK

SEQ ID NO:
MASISRPYGT KLRPDARKKE MLDKFFNTLT KGQRVFADLA LCIYGSLTLE MAKSLEPESD

2648
SELVCAIGWF RLVDKTIWSK DGIKQENLVK QYEAYSGKEA SEVVKTYLNS PSSDKYVWID

(Variant
CRQKFLRFQR ELGTRNLSED FECMLFEQYI RLTKGEIEGY AAISNMFGNG EKEDRSKKRM

Cas12i4)
YATRMKDWLE ANENITWEQY REALKNQLNA KNLEQVVANY KGNAGGADPF FKYSFSKEGM

VSKKEHAQQL DKFKTVLKNK ARDLNFPNKE KLKQYLEAEI GIPVDANVYS QMFSNGVSEV

QPKTTRNMSF SNEKLDLLTE LKDLNKGDGF EYAREVLNGF FDSELHTTED KFNITSRYLG

GDKSNRLSKL YKIWKKEGVD CEEGIQQFCE AVKDKMGQIP IRNVLKYLWQ FRETVSAEDF

EAAAKANHLE EKISRVKAHP IVISNRYWAF GTSALVGNIM PADKRHQGEY AGQNFKMWLE

AELHYDGKKA KHHLPFYNAR FFEEVYCYHP SVAEITPFKT KQFGCEIGKD IPDYVSVALK

DNPYKKATKR ILRAIYNPVA NTTGVDKTTN CSFMIKREND EYKLVINRKI SRDRPKRIEV

GRTIMGYDRN QTASDTYWIG RLVPPGTRGA YRIGEWSVQY IKSGPVLSST QGVNNSTTDQ

LVYNGMPSSS ERFKAWKKAR MAFIRKLIRQ LNDEGLESKG QDYIPENPSS FDVRGETLYV

FNSNYLKALV SKHRKAKKPV EGILDEIEAW TSKDKDSCSL MRLSSLSDAS MQGIASLKSL

INSYFNKNGC KTIEDKEKEN PVLYAKLVEV EQRRINKRSE KVGRIAGSLE QLALLNGVEV

VIGEADLGEV EKGKSKKQNS RNMDWCAKQV AQRLEYKLAF HGIGYFGVNP MYTSHQDPFE

HRRVADHIVM RARFEEVNVE NIAEWHVRNF SNYLRADSGT GLYYKQATMD FLKHYGLEEH

AEGLENKKIK FYDFRKILED KNLTSVIIPK RGGRIYMATN PVTSDSTPIT YAGKTYNRCN

ADEVAAANIV ISVLAPRSKK NREQDDIPLI TKKAESKSPP KDRKRSKTSQ LPQK

SEQ ID NO:
MASISRPYGT KLRPDARKKE MLDKFENTLT KGQRVFADLA LVIYHDLYLR MAKSLEPESD

2649
SELVCAIGWF RLVDKTIWSK DGIKQENLVK QYEAYSGKEA SEVVKTYLNS PSSDKYVWID

(Variant
CRQKFLRFQR ELGTRNLSED FECMLFEQYI RLTKGEIEGY AAISNMFGNG EKEDRSKKRM

Cas12i4)
YATRMKDWLE ANENITWEQY REALKNQLNA KNLEQVVANY KGNAGGADPF FKYSFSKEGM

VSKKEHAQQL DKFKTVLKNK ARDLNFPNKE KLKQYLEAEI GIPVDANVYS QMFSNGVSEV

QPKTTRNMSF SNEKLDLLTE LKDLNKGDGF EYAREVLNGF FDSELHTTED KFNITSRYLG

GDKSNRLSKL YKIWKKEGVD CEEGIQQFCE AVKDKMGQIP IRNVLKYLWQ FRETVSAEDF

EAAAKANHLE EKISRVKAHP IVISNRYWAF GTSALVGNIM PADKRHQGEY AGQNFKMWLR

AELHYDGKKA KHHLPFYNAR FFEEVYCYHP SVAEITPFKT KQFGCEIGKD IPDYVSVALK

DNPYKKATKR ILRAIYNPVA NTTRVDKTIN CSFMIKREND EYKLVINRKI SRDPRKRIEV

GRTIMGYDRN QTASDTYWIG RLVPPGTRGA YRIGEWSVQY IKSGPVLSST QGVNNSTTDQ

LVYNGMPSSS ERFKAWKKAR MAFIRKLIRQ LNDEGLESKG QDYIPENPSS FDVRGETLYV

FNSNYLKALV SKHRKAKKPV EGILDEIEAW TSKDKDSCSL MRLSSLSDAS MQGIASLKSL

INSYFNKNGC KTIEDKEKEN PVLYAKLVEV EQRRINKRSE KVGRIAGSLE QLALLNGVEV

VIGEADLGEV EKGKSKKQNS RNMDWCAKQV AQRLEYKLAF HGIGYFGVNP MYTSHQDPFE

HRRVADHIVM RARFEEVNVE NIAEWHVRNF SNYLRADSGT GLYYKQATMD FLKHYGLEEH

AEGLENKKIK FYDERKILED KNLTSVIIPK RGGRIYMATN PVTSDSTPIT YAGKTYNRCN

ADEVAAANIV ISVLAPRSKK NREQDDIPLI TKKAESKSPP KDRKRSKTSQ LPQK

SEQ ID NO:
MSNKEKNASETRKAYTTKMIPRSHDRMKLLGNFMDYLMDGTPIFFELWNQFGGGIDRDI

2650
ISGTANKDKISDDLLLAVNWFKVMPINSKPQGVSPSNLANLFQQYSGSEPDIQAQEYFA

(Cas12i1 of
SNFDTEKHQWKDMRVEYERLLAELQLSRSDMHHDLKLMYKEKCIGLSLSTAHYITSVMF

SEQ ID NO: 3
GTGAKNNRQTKHQFYSKVIQLLEESTQINSVEQLASIILKAGDCDSYRKLRIRCSRKGA

of U.S. Pat.
TPSILKIVQDYELGINHDDEVNVPSLIANLKEKLGRFEYECEWKCMEKIKAFLASKVGP

No.
YYLGSYSAMLENALSPIKGMTTKNCKFVLKQIDAKNDIKYENEPFGKIVEGFFDSPYFE

10,808,245)
SDTNVKWVLHPHHIGESNIKTLWEDLNAIHSKYEEDIASLSEDKKEKRIKVYQGDVCQT

INTYCEEVGKEAKTPLVQLLRYLYSRKDDIAVDKIIDGITFLSKKHKVEKQKINPVIQK

YPSFNFGNNSKLLGKIISPKDKLKHNLKCNRNQVDNYIWIEIKVLNTKTMRWEKHHYAL

SSTRFLEEVYYPATSENPPDALAARFRTKINGYEGKPALSAEQIEQIRSAPVGLRKVKK

RQMRLEAARQQNLLPRYTWGKDFNINICKRGNNFEVTLATKVKKKKEKNYKVVLGYDAN

IVRKNTYAAIEAHANGDGVIDYNDLPVKPIESGFVTVESQVRDKSYDQLSYNGVKLLYC

KPHVESRRSFLEKYRNGTMKDNRGNNIQIDFMKDFEAIADDETSLYYFNMKYCKLLQSS

IRNHSSQAKEYREEIFELLRDGKLSVLKLSSLSNLSFVMFKVAKSLIGTYFGHLLKKPK

NSKSDVKAPPITDEDKQKADPEMFALRLALEEKRLNKVKSKKEVIANKIVAKALELRDK

YGPVLIKGENISDTTKKGKKSSTNSFLMDWLARGVANKVKEMVMMHQGLEFVEVNPNFT

SHQDPFVHKNPENTFRARYSRCTPSELTEKNRKEILSFLSDKPSKRPTNAYYNEGAMAF

LATYGLKKNDVLGVSLEKFKQIMANILHQRSEDQLLFPSRGGMFYLATYKLDADATSVN

WNGKQFWVCNADLVAAYNVGLVDIQKDFKKK

SEQ ID NO:
MSISNNNILPYNPKLLPDDRKHKMLVDTFNQLDLIRNNLHDMIIALYGALKYDNIKQFA

2651
SKEKPHISADALCSINWFRLVKTNERKPAIESNQIISKFIQYSGHTPDKYALSHITGNH

(Cas12i3 of
EPSHKWIDCREYAINYARIMHLSFSQFQDLATACLNCKILILNGTLTSSWAWGANSALF

SEQ ID NO:
GGSDKENFSVKAKILNSFIENLKDEMNTTKFQVVEKVCQQIGSSDAADLFDLYRSTVKD

14 of U.S.
GNRGPATGRNPKVMNLFSQDGEISSEQREDFIESFQKVMQEKNSKQIIPHLDKLKYHLV

Pat. No.
KQSGLYDIYSWAAAIKNANSTIVASNSSNLNTILNKTEKQQTFEELRKDEKIVACSKIL

10,808,245)
LSVNDTLPEDLHYNPSTSNLGKNLDVFFDLLNENSVHTIENKEEKNKIVKECVNQYMEE

CKGLNKPPMPVLLTFISDYAHKHQAQDFLSAAKMNFIDLKIKSIKVVPTVHGSSPYTWI

SNLSKKNKDGKMIRTPNSSLIGWIIPPEEIHDQKFAGQNPIIWAVLRVYCNNKWEMHHF

PFSDSRFFTEVYAYKPNLPYLPGGENRSKRFGYRHSTNLSNESRQILLDKSKYAKANKS

VLRCMENMTHNVVFDPKTSLNIRIKTDKNNSPVLDDKGRITFVMQINHRILEKYNNTKI

EIGDRILAYDQNQSENHTYAILQRTEEGSHAHQFNGWYVRVLETGKVTSIVQGLSGPID

QLNYDGMPVTSHKFNCWQADRSAFVSQFASLKISETETFDEAYQAINAQGAYTWNLFYL

RILRKALRVCHMENINQFREEILAISKNRLSPMSLGSLSQNSLKMIRAFKSIINCYMSR

MSFVDELQKKEGDLELHTIMRLTDNKLNDKRVEKINRASSELTNKAHSMGCKMIVGESD

LPVADSKTSKKQNVDRMDWCARALSHKVEYACKLMGLAYRGIPAYMSSHQDPLVHLVES

KRSVLRPRFVVADKSDVKQHHLDNLRRMLNSKTKVGTAVYYREAVELMCEELGIHKTDM

AKGKVSLSDFVDKFIGEKAIFPQRGGRFYMSTKRLTTGAKLICYSGSDVWLSDADEIAA

INIGMFVVCDQTGAFKKKKKEKLDDEECDILPFRPM

	Number	Date	Country
	63252832	Oct 2021	US
	63108110	Oct 2020	US

COMPOSITIONS COMPRISING AN RNA GUIDE TARGETING BCL11A AND USES THEREOF

Information

Publication Number

Date Filed

Date Published

Inventors

Original Assignees

CPC

International Classifications

Abstract

Description

Claims

PCT Information

Provisional Applications (2)