Interfering with disease: a progress report on siRNA-based therapeutics

Nat Rev Drug Discov. 2007 Jun;6(6):443-53. doi: 10.1038/nrd2310.


RNA interference (RNAi) quietly crept into biological research in the 1990s when unexpected gene-silencing phenomena in plants and flatworms first perplexed scientists. Following the demonstration of RNAi in mammalian cells in 2001, it was quickly realized that this highly specific mechanism of sequence-specific gene silencing might be harnessed to develop a new class of drugs that interfere with disease-causing or disease-promoting genes. Here we discuss the considerations that go into developing RNAi-based therapeutics starting from in vitro lead design and identification, to in vivo pre-clinical drug delivery and testing. We conclude by reviewing the latest clinical experience with RNAi therapeutics.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Clinical Trials as Topic
  • Drug Delivery Systems
  • Drug Stability
  • Humans
  • Liposomes
  • Polyethyleneimine / administration & dosage
  • Polymers / administration & dosage
  • RNA Interference
  • RNA, Small Interfering / therapeutic use*


  • Liposomes
  • Polymers
  • RNA, Small Interfering
  • Polyethyleneimine