Extended Dicer Substrate Agents and Methods for the Specific Inhibition of Gene Expression

摘要

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.

主权项

1. A nucleic acid molecule capable of reducing expression of a target gene comprising:
a first oligonucleotide strand of between 20 and 60 nucleotides in length comprising RNA, a 3′ terminus and a 5′ terminus, and a second oligonucleotide strand at least 19 nucleotides in length, comprising RNA, 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 comprises at least one single-stranded nucleotide; wherein said second oligonucleotide strand is sufficiently complementary to a target mRNA encoded by said target gene to reduce expression of said target gene when said nucleic acid molecule is introduced to a mammalian cell; and wherein said nucleic acid molecule reduces expression of said target gene.