Breaking down the barriers: siRNA delivery and endosome escape

Monika Dominska, Derek M. Dykxhoorn

Research output: Contribution to journalComment/debatepeer-review

469 Scopus citations


RNA interference (RNAi)-based technologies offer an attractive strategy for the sequence-specific silencing of disease-causing genes. The application of small interfering (si)RNAs as potential therapeutic agents requires safe and effective methods for their delivery to the cytoplasm of the target cells and tissues. Recent studies have shown significant progress in the development of targeting reagents that facilitate the recognition of and siRNA delivery to specific cell types. However, most of these delivery approaches are not optimized to enable the intracellular trafficking of the siRNAs into the cytoplasm where they must associate with the RNA-induced silencing complex (RISC) to direct the cleavage of mRNAs bearing complementary binding sites. In particular, the trafficking of siRNAs from endosomes into the cytoplasm represents a major rate-limiting step for many delivery approaches. This Commentary focuses on novel strategies designed to enhance endosomal escape and thereby increase the efficacy of siRNA-mediated gene silencing.

Original languageEnglish (US)
Pages (from-to)1183-1189
Number of pages7
JournalJournal of Cell Science
Issue number8
StatePublished - Apr 15 2010


  • Gene silencing
  • RNA interference
  • siRNA delivery
  • siRNA trafficking

ASJC Scopus subject areas

  • Cell Biology


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