Knocking down disease: a progress report on siRNA therapeutics

Nat Rev Genet. 2015 Sep;16(9):543-52. doi: 10.1038/nrg3978.


Small interfering RNAs (siRNAs), which downregulate gene expression guided by sequence complementarity, can be used therapeutically to block the synthesis of disease-causing proteins. The main obstacle to siRNA drugs - their delivery into the target cell cytosol - has been overcome to allow suppression of liver gene expression. Here, we review the results of recent clinical trials of siRNA therapeutics, which show efficient and durable gene knockdown in the liver, with signs of promising clinical outcomes and little toxicity. We also discuss the barriers to more widespread applications that target tissues besides the liver and the most promising avenues to overcome them.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Genetic Therapy / methods*
  • Humans
  • Liver Diseases* / genetics
  • Liver Diseases* / metabolism
  • Liver Diseases* / pathology
  • Liver Diseases* / therapy
  • Liver* / metabolism
  • Liver* / pathology
  • RNA, Small Interfering* / genetics
  • RNA, Small Interfering* / therapeutic use


  • RNA, Small Interfering