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.
Claims20
A double stranded ribonucleic acid (dsRNA) comprising a first oligonucleotide strand and a second oligonucleotide strand wherein said second strand is annealed to said first strand to form a duplex region of 21 nucleotides in length, wherein said first strand is 23 nucleotides in length and comprises at least 18 nucleotides with a 2′-O-methyl modified sugar moiety and at least one nucleotide with a 2′-fluoro modified sugar moiety, and said second strand is 21 nucleotides in length and comprises at least 12 nucleotides with a 2′-O-methyl modified sugar moiety and at least one nucleotide with a 2′-fluoro modified sugar moiety, wherein said first strand comprises one single-stranded nucleotide at the 3′ terminus and one single-stranded nucleotide the 5′ terminus, and wherein said second oligonucleotide strand is fully complementary to a target mRNA sequence along at least 19 ribonucleotides of the second strand.
A double stranded ribonucleic acid (dsRNA) comprising a first oligonucleotide strand and a second oligonucleotide strand wherein said second strand is annealed to said first strand to form a duplex region of 21 nucleotides in length, wherein said first strand is 23 nucleotides in length and comprises at least 18 nucleotides with a 2′-O-methyl modified sugar moiety and at least one nucleotide with a 2′-fluoro modified sugar moiety, and said second strand is 21 nucleotides in length and comprises at least 12 nucleotides with a 2′-O-methyl modified sugar moiety and at least one nucleotide with a 2′-fluoro modified sugar moiety, wherein said first strand comprises one single-stranded nucleotide at the 3′ terminus and one single-stranded nucleotide at the 5′ terminus, wherein the dsRNA comprises one or more phosphorothioate linkages, and wherein said second oligonucleotide strand is fully complementary to a target mRNA sequence along at least 19 ribonucleotides of the second strand, wherein the dsRNA is attached to a non-nucleic acid moiety at the 5′ terminus of the first strand.
Dependencies are inferred from the claim text.