open access

https://hdl.handle.net/2115/49693

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

英語

2012-07

Oxford University Press

Nucleic Acids Research

40(12)

5787-5793

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 genesilencing effect without loss of RNAi activity, was identified. Quantification of the remaining siRNA in HeLa-luc cells using a Heat-in-Triton (HIT) qRT-PCR revealed that the intracellular stability of the siRNA modified with 2'-OMe-4'-thioribonucleosides contributed significantly to the duration of its RNAi activity.

学術雑誌論文

Version of Record

0305-1048