title: 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 exogenous target firefly luciferase was capable of gene-silencing at levels greater than 80% in the absence of a carrier complex.
authors.affiliation: University of Ontario Institute of Technology , Faculty of Science, 2000 Simcoe Street North, Oshawa, Ontario L1H 7K4, Canada.
authors.forename: Brandon J
authors.initials: BJ
authors.lastname: Peel
authors.affiliation: University of Ontario Institute of Technology , Faculty of Science, 2000 Simcoe Street North, Oshawa, Ontario L1H 7K4, Canada.
authors.forename: Gordon
authors.initials: G
authors.lastname: Hagen
authors.affiliation: University of Ontario Institute of Technology , Faculty of Science, 2000 Simcoe Street North, Oshawa, Ontario L1H 7K4, Canada.
authors.forename: Kalaivani
authors.initials: K
authors.lastname: Krishnamurthy
authors.affiliation: University of Ontario Institute of Technology , Faculty of Science, 2000 Simcoe Street North, Oshawa, Ontario L1H 7K4, Canada.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Desaulniers
keywords: Short interfering RNAs; down regulation; gene expression; nucleic acid chemistry; oligonucleotides