title: Efficient synthesis and cell-based silencing activity of siRNAS that contain triazole backbone linkages.
abstract: An efficient synthesis of siRNAs modified at the backbone with a triazole functionality is reported. Through the use of 4,4'-dimethoxytrityl (DMT) phosphoramidite chemistry, triazole backbone dimers were site-specifically incorporated throughout various siRNAs targeting both firefly luciferase and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene transcripts as representatives of an exogenous and endogenous gene, respectively. Following the successful silencing of the firefly luciferase reporter gene, triazole-modified siRNAs were also found to be capable of silencing GAPDH in a dose-dependent manner. Backbone modifications approaching the 3'-end on the sense strand were tolerated without compromising siRNA potency. This study highlights the compatibility of triazole-modified siRNAs within the RNAi pathway, and the modification's potential to impart favorable properties to siRNAs designed to target other endogenous genes.
authors.affiliation: Faculty of Science, University of Ontario Institute of Technology, Oshawa, Ontario, Canada.
authors.forename: Tim C
authors.initials: TC
authors.lastname: Efthymiou
authors.forename: Vanthi
authors.initials: V
authors.lastname: Huynh
authors.forename: Jaymie
authors.initials: J
authors.lastname: Oentoro
authors.forename: Brandon
authors.initials: B
authors.lastname: Peel
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Desaulniers
mesh_terms: D001386:Azides / Q000737:chemistry; D001483:Base Sequence; D057930:Click Chemistry; D020868:Gene Silencing / Q000187:drug effects*; D008156:Luciferases / Q000037:antagonists & inhibitors; D008969:Molecular Sequence Data; D015394:Molecular Structure; D034741:RNA, Small Interfering / Q000138:chemical synthesis* / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D014230:Triazoles / Q000138:chemical synthesis / Q000494:pharmacology; D014320:Triphenylmethyl Compounds / Q000737:chemistry
chemical_list: D001386:Azides; D034741:RNA, Small Interfering; D014230:Triazoles; D014320:Triphenylmethyl Compounds; C060949:4,4'-dimethoxytrityl cation; D008156:Luciferases