期刊
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
卷 22, 期 17, 页码 5590-5594出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2012.07.006
关键词
Short interfering RNA; Alkyl linker; Gene silencing; RNA; Destabilization
资金
- National Sciences and Engineering Research Council
- Canada Foundation for Innovation
The most widely accepted mechanism of RNAi-silencing involves the RNA-induced silencing complex (RISC) liberating the active antisense strand from the sense strand of an siRNA duplex to form an active RISC-antisense complex. This involves cleaving the sense strand between positions 9 and 10 from the 50 end of the strand prior to dissociation. Destabilizing modifications near the center of the duplex in some cases can enhance the efficacy of the resultant construct and may trigger an alternative mechanism through which the sense strand is removed. By introducing alkyl spacers of varying lengths near or within the sense strand's cleavage site, this study illustrates that siRNAs, in most cases, retained potent RNAi-silencing activity. Our results highlight that by substituting the scissile phosphodiester linkage on the sense strand with non-cleavable alkyl chains provides a novel and alternative method to destabilize the central region of siRNAs. Crown Copyright (C) 2012 Published by Elsevier Ltd. All rights reserved.
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