Gene editing methods, systems, and compositions for treating spinal muscular atrophy
AssigneesThe Broad Institute, Inc., President and Fellows of Harvard College
InventorsDavid R. Liu, Mandana Arbab, Zaneta Matuszek
Life of this patent
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Abstract
Provided are compositions and methods for delivering biological moieties such as modified nucleic acids into cells to kill or reduce the growth of microorganisms. Such compositions and methods include the use of modified messenger RNAs, and are useful to treat or prevent microbial infection, or to improve a subject's heath or wellbeing.
Claims36
A method for deaminating a nucleobase in an SMN2 gene, the method comprising contacting the SMN2 gene with a base editor in association with a guide RNA (gRNA), wherein the gRNA comprises a spacer sequence selected from the group consisting of:
- (SEQ ID NO:
- 1)
- 5′-UUUCCUGCAAAUGAGAAAUU-3′;
- (SEQ ID NO:
- 2)
- 5′-GAUUUUGUCUAAAACCCUGUA-3′;
- (SEQ ID NO:
- 3)
- 5′-CUUAAUUUAAGGAAUGUGAG-3′;
- (SEQ ID NO:
- 4)
- 5′-UCCUUAAUUUAAGGAAUGUG-3′;
- (SEQ ID NO:
- 5)
- 5′-UUACUCCUUAAUUUAAGGAA-3′;
- (SEQ ID NO:
- 6)
- 5′-AAGGAGUAAGUCUGCCAGCA-3′;
- and
- (SEQ ID NO:
- 7)
- 5′-UUAAGGAGUAAGUCUGCCAG-3′.
2-3. (canceled)
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13-26. (canceled)
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A method for editing an SMN2 gene, the method comprising contacting the SMN2 gene with a nuclease in association with a guide RNA (gRNA), wherein the gRNA comprises a spacer sequence selected from the group consisting of:
- (SEQ ID NO:
- 8)
- 5′-AGUCUGCCAGCAUUAUGAAA-3′;
- (SEQ ID NO:
- 9)
- 5′-UCUGCCAGCAUUAUGAAAGU-3′;
- (SEQ ID NO:
- 10)
- 5′-CUGCCAGCAUUAUGAAAGUG-3′;
- (SEQ ID NO:
- 11)
- 5′-UGCCAGCAUUAUGAAAGUGA-3′;
- (SEQ ID NO:
- 12)
- 5′-AAAGUAAGAUUCACUUUCAU-3′;
- (SEQ ID NO:
- 13)
- 5′-AAAAGUAAGAUUCACUUUCA-3′;
- (SEQ ID NO:
- 14)
- 5′-CAAAAGUAAGAUUCACUUUC-3′;
- (SEQ ID NO:
- 15)
- 5′-UCUCAUUUGCAGGAAAUGCU-3′;
- (SEQ ID NO:
- 16)
- 5′-UGCAGGAAAUGCUGGCAUAG-3′;
- (SEQ ID NO:
- 17)
- 5′-AUUUAGUGCUGCUCUAUGCC-3′;
- (SEQ ID NO:
- 18)
- 5′-GCUCUAUGCCAGCAUUUCCUG-3′;
- and
- (SEQ ID NO:
- 19)
- 5′-AGTCTGCCAGCATTATGAAA-3.
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A guide RNA (gRNA) comprising a spacer sequence selected from the group consisting of:
- (SEQ ID NO:
- 1)
- 5′-UUUCCUGCAAAUGAGAAAUU-3′;
- (SEQ ID NO:
- 2)
- 5′-GAUUUUGUCUAAAACCCUGUA-3′;
- (SEQ ID NO:
- 3)
- 5′-CUUAAUUUAAGGAAUGUGAG-3′;
- (SEQ ID NO:
- 4)
- 5′-UCCUUAAUUUAAGGAAUGUG-3′;
- (SEQ ID NO:
- 5)
- 5′-UUACUCCUUAAUUUAAGGAA-3′;
- (SEQ ID NO:
- 6)
- 5′-AAGGAGUAAGUCUGCCAGCA-3′;
- (SEQ ID NO:
- 7)
- 5′-UUAAGGAGUAAGUCUGCCAG-3′;
- (SEQ ID NO:
- 19)
- 5′-AGTCTGCCAGCATTATGAAA-3′;
- (SEQ ID NO:
- 8)
- 5′-AGUCUGCCAGCAUUAUGAAA-3′;
- (SEQ ID NO:
- 9)
- 5′-UCUGCCAGCAUUAUGAAAGU-3′;
- (SEQ ID NO:
- 10)
- 5′-CUGCCAGCAUUAUGAAAGUG-3′;
- (SEQ ID NO:
- 11)
- 5′-UGCCAGCAUUAUGAAAGUGA-3′;
- (SEQ ID NO:
- 12)
- 5′-AAAGUAAGAUUCACUUUCAU-3′;
- (SEQ ID NO:
- 13)
- 5′-AAAAGUAAGAUUCACUUUCA-3′;
- (SEQ ID NO:
- 14)
- 5′-CAAAAGUAAGAUUCACUUUC-3′;
- (SEQ ID NO:
- 15)
- 5′-UCUCAUUUGCAGGAAAUGCU-3′;
- (SEQ ID NO:
- 16)
- 5′-UGCAGGAAAUGCUGGCAUAG-3′;
- (SEQ ID NO:
- 17)
- 5′-AUUUAGUGCUGCUCUAUGCC-3′;
- and
- (SEQ ID NO:
- 18)
- 5′-GCUCUAUGCCAGCAUUUCCUG-3′.
84-91. (canceled)
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Dependencies are inferred from the claim text.