Rational design leads to more potent RNA interference against hepatitis B virus: factors effecting silencing efficiency.

ABSTRACT: RNA interference (RNAi) can be an effective antiviral agent; however, overexpression of RNAi can be toxic through competition with the endogenous microRNA (miRNA) machinery. We used rational design to identify highly potent RNAi that is effective at nontoxic doses. A statistical analysis was conducted to pinpoint thermodynamic characteristics correlated with activity. Sequences were selected that conformed to a consensus internal stability profile (ISP) associated with active RNAi, and RNAi triggers were expressed in the context of an endogenous miRNA. These approaches yielded highly active hepatitis B virus (HBV) RNAi. A statistical analysis found a correlation between activity and nucleation by binding within the seed sequence to accessible regions in the target RNA. Guide strands were s

SUBMITTER: Keck K 

PROVIDER: S-EPMC2770508 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature