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, Robert J. Desnick, Makiko Yasuda
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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.
Claims34
A double-stranded ribonucleic acid (dsRNA) for inhibiting expression of ALAS1, wherein said dsRNA comprises a sense strand and an antisense strand 15-30 base pairs in length and the antisense strand is complementary to at least 15 contiguous nucleotides of SEQ ID NO:
- 1 or 382.
A double-stranded ribonucleic acid (dsRNA) for inhibiting expression of ALAS1, wherein said dsRNA comprises a sense strand and an antisense strand, the antisense strand comprising a region of complementarity to an ALAS1 RNA transcript, which antisense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the antisense sequence of AD-58882 (SEQ ID NO:
- 3434) or one of the antisense sequences listed in any one of Tables 2, 3, 6, 7, 8, 9, 14, 15, 18, or 20.
(canceled)
-8. (canceled)
(canceled)
-14. (canceled)
(canceled)
-31. (canceled)
-41. (canceled)
(canceled)
-58. (canceled)
-61. (canceled)
-68. (canceled)
-72. (canceled)
-77. (canceled)
A double stranded RNAi (dsRNA) comprising a sense strand complementary to an antisense strand, wherein said antisense strand comprises a region of complementarity to an ALAS1 RNA transcript, wherein each strand has about 14 to about 30 nucleotides, wherein said dsRNA is represented by formula (III):
- sense:5′np-Na-(XXX)i-Nb-YYY-Nb-(ZZZ)j-Na-nq3′
- antisense:3′np′-Na′-(X′X′X′)k-Nb′-Y′Y′Y′-Nb′-(Z′Z′Z′)l-Na′-nq′5′ (III)
- wherein:
- i, j, k, and 1 are each independently 0 or 1;
- p, p′, q, and q′ are each independently 0-6;
- each Na and Na′ independently represents an oligonucleotide sequence comprising 0-25 nucleotides which are either modified or unmodified or combinations thereof, each sequence comprising at least two differently modified nucleotides;
- each Nb and Nb′ independently represents an oligonucleotide sequence comprising 0-10 nucleotides which are either modified or unmodified or combinations thereof;
- each np, np′, nq, and nq′ independently represents an overhang nucleotide;
- XXX, YYY, ZZZ, X′X′X′, Y′Y′Y′, and Z′Z′Z′ each independently represent one motif of three identical modifications on three consecutive nucleotides;
- modifications on Nb differ from the modification on Y and modifications on Nb′ differ from the modification on Y′.
-154. (canceled)
Dependencies are inferred from the claim text.