Compositions and methods for inhibiting expression of the ALAS1 gene
AssigneesAlnylam Pharmaceuticals, Inc., Icahn School of Medicine at Mount Sinai
InventorsBrian Bettencourt, Kevin Fitzgerald, William Querbes, Makiko Yasuda, Robert J. Desnick
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Abstract
The invention relates to double-stranded ribonucleic acid (dsRNA) compositions targeting the ALAS1 gene, and methods of using such dsRNA compositions to alter (e.g., inhibit) expression of ALAS1.
Claims45
A method of treating a disorder related to ALAS1 expression, comprising administering to a subject in need of such treatment a therapeutically effective amount of a double-stranded ribonucleic acid (dsRNA), wherein said dsRNA comprises a sense strand and an antisense strand, each of which are 15-30 nucleotides in length, wherein the antisense strand comprises a region of complementarity to an ALAS1 RNA and comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from SEQ ID NO:
- 1296, and wherein the antisense strand is complementary to at least nucleotides 871-889 of SEQ ID NO:
- 1.
A method of treating a porphyria comprising administering to a subject in need of such treatment a double-stranded ribonucleic acid (dsRNA), wherein said dsRNA comprises a sense strand and an antisense strand each of which are 15-30 nucleotides in length, and wherein the antisense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from SEQ ID NO:
- 1296.
A method of treating a subject with an elevated level of ALA, PBG, or both ALA and PBG, the method comprising administering to the subject a double-stranded ribonucleic acid (dsRNA), wherein said dsRNA comprises a sense strand and an antisense strand each of which are 15-30 nucleotides in length and the antisense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from SEQ ID NO:
- 1296.
A method of treating a subject having a porphyria, the method comprising administering to the subject a double-stranded ribonucleic acid (dsRNA), wherein said dsRNA comprises a sense strand and an antisense strand each of which are 19-24 nucleotides in length, wherein
- (i) the antisense strand comprises at least 15 contiguous nucleotides of SEQ ID NO:
- 1296,
- (ii) the sense strand comprises at least 15 contiguous nucleotides of SEQ ID NO:1295,
- (iii) the dsRNA comprises a ligand attached to the 3′ end of the sense strand and having the structure
- (iv) the nucleotides of the dsRNA are modified on the entire length of the sense strand and the antisense strand with 2′-O-methyl and 2′-fluoro modifications, and
- (v) the antisense strand comprises a 3′-overhang of two nucleotides.
Dependencies are inferred from the claim text.