Conjugation and Evaluation of Small Hydrophobic Molecules to Triazole-Linked siRNAs.

ABSTRACT: Short interfering RNAs (siRNAs) have tremendous potential as a new class of next-generation therapeutics; however, their progress is lagging due to issues related to stability, biodistribution, and cell-membrane permeability. To overcome these issues, there is widespread interest in chemically modifying siRNAs. In this study, siRNAs that contain a triazole-backbone unit with pyrimidine-modified hydrophobic substituents were synthesized and examined for their gene-silencing activity. In our study, we generated a library of siRNAs that target both a plasmid reporter system and an endogenous gene target, bcl-2. Our results indicate that these unique modifications are well tolerated within the RNA interference pathway. In addition, a cholesterol-modified triazole-linked siRNA targeting the exo

SUBMITTER: Peel BJ 

PROVIDER: S-EPMC4329592 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature