RNA interference using boranophosphate siRNAs: structure-activity relationships.

Published online

Journal Article

In RNA interference (RNAi), short double-stranded RNA (known as siRNA) inhibits expression from homologous genes. Clinical or pre-clinical use of siRNAs is likely to require stabilizing modifications because of the prevalence of intracellular and extracellular nucleases. In order to examine the effect of modification on siRNA efficacy and stability, we developed a new method for synthesizing stereoregular boranophosphate siRNAs. This work demonstrates that boranophosphate siRNAs are consistently more effective than siRNAs with the widely used phosphorothioate modification. Furthermore, boranophosphate siRNAs are frequently more active than native siRNA if the center of the antisense strand is not modified. Boranophosphate modification also increases siRNA potency. The finding that boranophosphate siRNAs are at least ten times more nuclease resistant than unmodified siRNAs may explain some of the positive effects of boranophosphate modification. The biochemical properties of boranophosphate siRNAs make them promising candidates for an RNAi-based therapeutic.

Full Text

Duke Authors

Cited Authors

  • Hall, AHS; Wan, J; Shaughnessy, EE; Ramsay Shaw, B; Alexander, KA

Published Date

  • 2004

Published In

Volume / Issue

  • 32 / 20

Start / End Page

  • 5991 - 6000

PubMed ID

  • 15545637

Pubmed Central ID

  • 15545637

Electronic International Standard Serial Number (EISSN)

  • 1362-4962

Digital Object Identifier (DOI)

  • 10.1093/nar/gkh936

Language

  • eng

Conference Location

  • England