Therapeutic application of RNAi: is mRNA targeting finally ready for prime time?

J Clin Invest. 2007 Dec;117(12):3633-41. doi: 10.1172/JCI34129.


With unprecedented speed, RNA interference (RNAi) has advanced from its basic discovery in lower organisms to becoming a powerful genetic tool and perhaps our single most promising biotherapeutic for a wide array of diseases. Numerous studies document RNAi efficacy in laboratory animals, and the first clinical trials are underway and thus far suggest that RNAi is safe to use in humans. Yet substantial hurdles have also surfaced and must be surmounted before therapeutic RNAi applications can become a standard therapy. Here we review the most critical roadblocks and concerns for clinical RNAi transition, delivery, and safety. We highlight emerging solutions and concurrently discuss novel therapeutic RNAi-based concepts. The current rapid advances create realistic optimism that the establishment of RNAi as a new and potent clinical modality in humans is near.

Publication types

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

MeSH terms

  • Animals
  • Clinical Trials as Topic
  • Drug Delivery Systems*
  • Drug-Related Side Effects and Adverse Reactions
  • Humans
  • RNA Interference / drug effects*
  • RNA, Messenger / antagonists & inhibitors*
  • RNA, Small Interfering / adverse effects
  • RNA, Small Interfering / chemistry
  • RNA, Small Interfering / therapeutic use*


  • RNA, Messenger
  • RNA, Small Interfering