Modified Short Interfering Nucleic Acid (siNA) Molecules and Uses Thereof
AssigneeAligos Therapeutics, Inc.
InventorsLeonid Beigelman, Vivek Kumar Rajwanshi, Markus Hossbach, Rajendra K. Pandey, Jin Hong, Laxman Eltepu, Saul Martinez Montero, N. Tilani S. De Costa
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Abstract
Disclosed herein are short interfering nucleic acid (siNA) molecules comprising modified nucleotides and uses thereof. The siNA molecules may be double stranded and comprise modified nucleotides selected from 2′-O-methyl nucleotides and 2′-fluoro nucleotides. Further disclosed herein are siNA molecules comprising (a) a phosphorylation blocker, conjugated moiety, or 5′-stabilized end cap; and (b) a short interfering nucleic acid (siNA).
Claims30
A double stranded short interfering nucleic acid (siNA) comprising:
- (a) a sense strand comprising 19-21 nucleotides in a nucleic acid sequence that is at least 80% identical to SEQ ID NO:
- 40, wherein 15 or more of the nucleotides are modified nucleotides independently selected from a 2′-O-methyl nucleotide and a 2′-fluoro nucleotide, and wherein at least one modified nucleotide is a 2′-O-methyl nucleotide and at least one modified nucleotide is a 2′-fluoro nucleotide;
- and
- (b) an antisense strand comprising 19-21 nucleotides in a nucleic acid sequence that is at least 80% complementary to SEQ ID NO:
- 40, wherein 15 or more of the nucleotides are modified nucleotides independently selected from a 2′-O-methyl nucleotide and a 2′-fluoro nucleotide, and wherein at least one modified nucleotide is a 2′-O-methyl nucleotide and at least one modified nucleotide is a 2′-fluoro nucleotide.
A double stranded short interfering nucleic acid (siNA) comprising:
- (a) a sense strand comprising 19 nucleotides, wherein 2′-fluoro nucleotides are at positions 5 and 7-9 from the 5′ end of the sense strand, and wherein 2′-O-methyl nucleotides are at positions 1-4, 6, and 10-19 from the 5′ end of the sense strand;
- and
- (b) an antisense strand comprising 21 nucleotides, wherein 2′-fluoro nucleotides are at positions 2, 6, 14, and 16 from the 5′ end of the antisense strand, and wherein 2′-O-methyl nucleotides are at positions 1, 3-5, 7-13, 15, and 17-21 from the 5′ end of the antisense strand.
A short interfering nucleic acid (siNA) molecule comprising:
- (a) a sense strand comprising SEQ ID NO:
- 438 or SEQ ID NO:
- 435, and
- (b) an antisense strand comprising a sequence selected from any one of SEQ ID NOs:
- 501-519, SEQ ID NO:
- 521, SEQ ID NO:
- 522, SEQ ID NO:
- 537, SEQ ID NO:
- 538, and SEQ ID NO:
- 539.
A double stranded short interfering nucleic acid (siNA) comprising:
- (a) a sense strand of
- (SEQ ID NO:
- 438)
- 5′-mGpsmUpsmGmGfUmGfGfAfCmUmUmCmUmCmUmCmAmAmU-p-
- ps2-GalNAc4-3′
- and an antisense strand of
- (SEQ ID NO:
- 501)
- 5′-mApsfUpsmUmGmAfGmAmGmAmAmGmUmCfCmAfCmCmAmCpsm
- GpsmA-3′;
- (b) a sense strand of
- (SEQ ID NO:
- 438)
- 5′-mGpsmUpsmGmGfUmGfGfAfCmUmUmCmUmCmUmCmAmAmU-p-
- ps2-GalNAc4-3′
- and an antisense strand of
- (SEQ ID NO:
- 521)
- 5′-mApsfUpsmUmGmAfGmAfGfAmAmGmUmCfCmAfCmCmAmCpsm
- GpsmA-3′;
- (c) a sense strand of
- (SEQ ID NO:
- 438)
- 5′-mGpsmUpsmGmGfUmGfGfAfCmUmUmCmUmCmUmCmAmAmU-p-
- ps2-GalNAc4-3′
- and an antisense strand of
- (SEQ ID NO:
- 522)
- 5′-mApsfUpsmUmGfAmGmAfGmAmAmGmUmCfCmAmCfCmAmCpsm
- GpsmA-3′;
- (d) a sense strand of
- (SEQ ID NO:
- 438)
- 5′-mGpsmUpsmGmGfUmGfGfAfCmUmUmCmUmCmUmCmAmAmU-
- p-ps2-GalNAc4-3′
- and an antisense strand of
- (SEQ ID NO:
- 537)
- 5′-mApsf4PpsmUmGmAfGmAmGmAmAmGmUmCfCmAfCmCmAmCp
- smGpsmA-3′;
- (e) a sense strand of
- (SEQ ID NO:
- 438)
- 5′-mGpsmUpsmGmGfUmGfGfAfCmUmUmCmUmCmUmCmAmAmU-
- p-ps2-GalNAc4-3′
- and an antisense strand of
- (SEQ ID NO:
- 538)
- 5′-mApsfUpsmUmGmAfGmAmGmAmAmGmUmCf2PmAfCmCmAmCp
- smGpsmA-3′;
- or
- (f) a sense strand of
- (SEQ ID NO:
- 438)
- 5′-mGpsmUpsmGmGfUmGfGfAfCmUmUmCmUmCmUmCmAmAmU-p-
- ps2-GalNAc4-3′
- and an antisense strand of
- (SEQ ID NO:
- 539)
- 5′-mApsfUpsmUmGmAfGmAmGmAmAmGmUmCfCmAfXmCmAmCpsm
- GpsmA-3′,
- wherein fX is
Dependencies are inferred from the claim text.