Chemical modification patterns compatible with high potency dicer-substrate small interfering RNAs

Michael A. Collingwood, Scott D. Rose, Lingyan Huang, Chris Hillier, Mohammad Amarzguioui, Merete T. Wiiger, Harris S. Soifer, John J. Rossi, Mark A. Behlke

Research output: Contribution to journalArticlepeer-review

84 Citations (Scopus)

Abstract

Dicer-substrate small interfering RNAs (DsiRNAs) are synthetic RNA duplexes that are processed by Dicer into 21-mer species and show improved potency as triggers of RNA interference, particularly when used at low dose. Chemical modification patterns that are compatible with high potency 21-mer small interfering RNAs have been reported by several groups. However, modification patterns have not been studied for Dicer-substrate duplexes. We therefore synthesized a series of chemically modified 27-mer DsiRNAs and correlated modification patterns with functional potency. Some modification patterns profoundly reduced function although other patterns maintained high potency. Effects of sequence context were observed, where the relative potency of modification patterns varied between sites.

Original languageEnglish
Pages (from-to)187-200
Number of pages14
JournalOligonucleotides
Volume18
Issue number2
DOIs
Publication statusPublished - 1 Jun 2008

Keywords

  • DsiRNAs
  • RNA
  • modification patterns

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