Methods and compositions for the specific inhibition of KRAS by asymmetric double-stranded RNA
AssigneeDicerna Pharmaceuticals, Inc.
InventorBob D. Brown
Life of this patent
Estimating the term…
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.
Claims31
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 has a length which is at least 25 and at most 35 nucleotides, wherein said second nucleic acid strand is sufficiently complementary to a target KRAS cDNA sequence selected from the group consisting of SEQ ID NOs:
- 161, 164, 4909, 4938, 4952, 6863, and 8340 along at least 19 nucleotides of said second nucleic acid strand length to reduce KRAS target gene expression when said dsNA is introduced into a mammalian cell.
A composition possessing KRAS inhibitory activity consisting essentially of 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, wherein said second nucleic acid strand of said dsNA comprises 1-5 single-stranded nucleotides at its 3′ terminus, wherein said second nucleic acid strand is complementary to a target KRAS cDNA sequence selected from the group consisting of SEQ ID NOs:
- 161, 164, 4909, 4938, 4952, 6863, and 8340 along at least 19 nucleotides of said second nucleic acid strand length and said dsNA reduces KRAS target gene expression when said dsNA is introduced into a mammalian cell.
An isolated double stranded nucleic acid (dsNA) comprising first and second nucleic acid strands, wherein said second nucleic acid strand is 21 to 35 nucleotides in length, wherein at least 19 consecutive nucleotide residues of the first nucleic acid strand are complementary to residues of the second nucleic acid strand, wherein the second nucleic acid strand comprises a nucleotide sequence that is perfectly complementary to at least 21 contiguous nucleotides of SEQ ID NO:
- 4952 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.