Intracellular stability of 2'-OMe-4'-thioribonucleoside modified siRNA leads to long-term RNAi effect.

ABSTRACT: Chemically modified siRNAs are expected to have resistance toward nuclease degradation and good thermal stability in duplex formation for in vivo applications. We have recently found that 2'-OMe-4'-thioRNA, a hybrid chemical modification based on 2'-OMeRNA and 4'-thioRNA, has high hybridization affinity for complementary RNA and significant resistance toward degradation in human plasma. These results prompted us to develop chemically modified siRNAs using 2'-OMe-4'-thioribonucleosides for therapeutic application. Effective modification patterns were screened with a luciferase reporter assay. The best modification pattern of siRNA, which conferred duration of the gene-silencing effect without loss of RNAi activity, was identified. Quantification of the remaining siRNA in HeLa-luc cells usin

SUBMITTER: Takahashi M 

PROVIDER: S-EPMC3384325 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature