Running interference: Prospects and obstacles to using small interfering RNAs as small molecule drugs

Derek M Dykxhoorn, Judy Lieberman

Research output: Contribution to journalArticlepeer-review

96 Scopus citations

Abstract

RNA interference (RNAi) is a well-conserved, ubiquitous, endogenous mechanism that uses small noncoding RNAs to silence gene expression. The endogenous small RNAs, called microRNAs, are processed from hairpin precursors and regulate important genes involved in cell death, differentiation, and development. RNAi also protects the genome from invading genetic elements, encoded by transposons and viruses. When small double-stranded RNAs, called small interfering (si)RNAs, are introduced into cells, they bind to the endogenous RNAi machinery to disrupt the expression of mRNAs containing complementary sequences with high specificity. Any disease-causing gene and any cell type or tissue can potentially be targeted. This technique has been rapidly utilized for gene-function analysis and drug-target discovery and validation. Harnessing RNAi also holds great promise for therapy, although introducing siRNAs into cells in vivo remains an important obstacle. Pilot siRNA clinical studies began just three years after the discovery that RNAi works in mammalian cells. This review discusses recent progress and obstacles to using siRNAs as small molecule drugs.

Original languageEnglish
Pages (from-to)377-402
Number of pages26
JournalAnnual Review of Biomedical Engineering
Volume8
DOIs
StatePublished - Sep 7 2006
Externally publishedYes

Keywords

  • Drug development
  • In vivo delivery
  • RNA interference
  • Therapy

ASJC Scopus subject areas

  • Biophysics
  • Biomedical Engineering

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