Extended dicer substrate agents and methods for the specific inhibition of gene expression
AssigneeDicerna Pharmaceuticals, Inc.
InventorBob Dale Brown
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Abstract
The invention provides compositions and methods for reducing expression of a target gene in a cell, involving contacting a cell with an isolated double stranded nucleic acid (dsNA) in an amount effective to reduce expression of a target gene in a cell. The dsNAs of the invention possess a single stranded extension (in most embodiments, the single stranded extension comprises at least one modified nucleotide and/or phosphate back bone modification). Such single stranded extended Dicer-substrate siRNAs (DsiRNAs) were demonstrated to be effective RNA inhibitory agents compared to corresponding double stranded DsiRNAs.
Claims63
A double stranded nucleic acid capable of reducing expression of a target gene comprising:
- a first oligonucleotide strand of 33 to 49 nucleotides in length comprising a 3′ terminus and a 5 terminus, and
- a second oligonucleotide strand of 19-39 nucleotides in length, comprising a 3′ terminus and a 5′ terminus,
- wherein said second strand is annealed to said first strand to form a duplex region of 18 to 30 nucleotides in length,
- wherein the 3′ terminus of said first strand consists of 10-30 unpaired nucleotides that overhang the 5′ terminus of the second strand, wherein at least one of the 10-30 unpaired nucleotides is a modified nucleotide, wherein the modified nucleotide comprises a 2′-O-methyl and/or a 2′-fluoro modified sugar moiety;
- and
- wherein said second strand is sufficiently complementary to a target RNA along at least 19 nucleotides of said second strand length to reduce target gene expression when said double stranded nucleic acid is introduced into a mammalian cell.
Dependencies are inferred from the claim text.