In vivo activity of nuclease-resistant siRNAs.

Journal Article (Journal Article)

Chemical modifications have been incorporated into short interfering RNAs (siRNAs) without reducing their ability to inhibit gene expression in mammalian cells grown in vitro. In this study, we begin to assess the potential utility of 2'-modified siRNAs in mammals. We demonstrate that siRNA modified with 2'-fluoro (2'-F) pyrimidines are functional in cell culture and have a greatly increased stability and a prolonged half-life in human plasma as compared to 2'-OH containing siRNAs. Moreover, we show that the 2'-F containing siRNAs are functional in mice and can inhibit the expression of a target gene in vivo. However, even though the modified siRNAs have greatly increased resistance to nuclease degradation in plasma, this increase in stability did not translate into enhanced or prolonged inhibitory activity of target gene reduction in mice following tail vein injection. Thus, this study shows that 2'-F modified siRNAs are functional in vivo, but that they are not necessarily more potent than unmodified siRNAs in animals.

Full Text

Duke Authors

Cited Authors

  • Layzer, JM; McCaffrey, AP; Tanner, AK; Huang, Z; Kay, MA; Sullenger, BA

Published Date

  • May 2004

Published In

Volume / Issue

  • 10 / 5

Start / End Page

  • 766 - 771

PubMed ID

  • 15100431

Pubmed Central ID

  • PMC1370566

International Standard Serial Number (ISSN)

  • 1355-8382

Digital Object Identifier (DOI)

  • 10.1261/rna.5239604


  • eng

Conference Location

  • United States