REDUCTION OF OFF-TARGET RNA INTERFERENCE TOXICITY

摘要

The present invention is directed to RNA interference (RNAi) molecules targeted against a nucleic acid sequence, and methods of using these RNAi molecules to reduce off-target toxicity.

主权项

1. A nucleic acid encoding an artificial primary miRNA transcript (pri-miRNA) consisting of, in order of position, a 5′-flanking region, a first siRNA region, a loop region, a second siRNA region, and a 3′-flanking region, wherein the 5′-flanking region comprises:
(a) a 5′-joining sequence contiguously linked to the first siRNA region; (b) a 5′-bulge sequence positioned upstream from the 5′ joining sequence; and (c) a 5′-spacer sequence positioned upstream from the 5′-bulge sequence.