Synthesis of small interfering RNAs containing acetal-type nucleoside analogs at their 3′-ends and analysis of their silencing activity and their ability to bind to the Argonaute2 PAZ domain

Abstract

In this study, we aimed to create small interfering RNAs (siRNAs) with increased silencing activities and nuclease resistance properties. Therefore, we designed and synthesized five types of siRNA containing acetal-type nucleoside analogs at their 3′-dangling ends. We found that the siRNA containing 1-O-(2,2,2-trifluoroethyl)-β-D-ribofuranose at the 3′-dangling end was the most potent among the synthesized siRNAs and showed more resistance to nucleolytic degradation by a 3′ exonuclease than a natural RNA did. Thus, modification of siRNAs by addition of 1-O-(2,2,2-trifluoroethyl)-β-D-ribofuranose may hold promise as a means of improving the silencing activity and nuclease resistance of siRNAs.