Chemical modification of short small hairpin RNAs for inhibition of gene expression

摘要

Aspects of the present invention include the production and use of chemically modified RNAi agents (e.g., shRNAs) in gene silencing applications. The chemically modified RNAi agents disclosed herein have reduced immunostimulatory activity, increased serum stability, or both, as compared to a corresponding RNAi agent not having the chemical modification. Compositions containing chemically modified RNAi agents according to aspects of the present invention (including pharmaceutical compositions) and kits containing the same are also provided.

主权项

1. A small hairpin RNA (shRNA) consisting of:
an antisense sequence consisting of about 16 to about 19 nucleotides; a sense sequence consisting of about 11 to about 19 nucleotides, wherein the sense sequence is substantially complementary to the antisense sequence; a loop region connecting the antisense and sense sequences; and optionally, an overhang region, a conjugate moiety, and/or a detectable label, wherein the loop region comprises at least one of the following chemical modifications: 2′-H, 2′-O-alkyl, or 2′-halo modification of one or more nucleotides or one or more phosphorothioate modifications of the backbone; wherein the at least one chemical modification confers reduced immunostimulatory activity, increased serum stability, or both, as compared to a corresponding shRNA not having the chemical modification.