Methods and compositions for the specific inhibition of KRAS by asymmetric double-stranded RNA
AssigneeDicerna Pharmaceuticals, Inc.
InventorBob D. Brown
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Abstract
This invention relates to compounds, compositions, and methods useful for reducing KRAS target RNA and protein levels via use of Dicer substrate siRNA (DsiRNA) agents possessing asymmetric end structures.
Claims57
An isolated double stranded nucleic acid (dsNA) comprising first and second nucleic acid strands and a duplex region of at least 25 base pairs, wherein each of said first and second nucleic acid strands comprises RNA and has a length which is at least 25 and at most 35 nucleotides, wherein said second oligonucleotide strand is sufficiently complementary to SEQ ID NO:
- 161 along at least 19 nucleotides of said second oligonucleotide strand length to reduce KRAS target gene expression when said double stranded nucleic acid is introduced into a mammalian cell.
A composition possessing KRAS inhibitory activity consisting essentially of an isolated double stranded ribonucleic acid (dsNA) comprising first and second nucleic acid strands and a duplex region of at least 25 base pairs, wherein said second strand of said dsNA comprises 1-5 single-stranded nucleotides at its 3′ terminus, wherein said second oligonucleotide strand is sufficiently complementary to SEQ ID NO:
- 161 along at least 19 nucleotides of said second oligonucleotide strand length to reduce KRAS target gene expression when said double stranded nucleic acid is introduced into a mammalian cell.
An isolated double stranded nucleic acid (dsNA) comprising first and second nucleic acid strands, wherein each of said first and second nucleic acid strands comprises RNA, wherein said second oligonucleotide strand is 19 to 35 nucleotides in length and comprises a sequence that is completely complementary to SEQ ID NO:
- 6863 and wherein said dsNA reduces KRAS target gene expression when said double stranded nucleic acid is introduced into a mammalian cell.
Dependencies are inferred from the claim text.