Genetic pharmacology: progresses in siRNA delivery and therapeutic applications

Gene Ther. 2017 Mar;24(3):151-156. doi: 10.1038/gt.2017.6. Epub 2017 Jan 25.


In the RNA interference process, the catalytic degradation of an endogenous mRNA results from the Watson-Crick complementary recognition by either a small silencing synthetic double-stranded ribonucleotide (siRNA) or by a small hairpin RNA (shRNA) produced in the cell by transcription from a DNA template. This interference process ideally results in an exquisitely specific mRNA suppression. The present review is dedicated to siRNAs. It describes the mechanism of RNA silencing and the main siRNA delivery techniques, with a focus on siRNA self-complexing to cationic lipids to form nanoparticles, which are called lipoplexes. The addition to lipoplexes of an anionic polymer leads to the ternary formulation APIRL (Anionic-Polymer-Interfering-RNA-Lipoplexes) with increased in vivo stability and biological efficacy. In terms of clinical development, the review focuses on therapeutic applications by intravenous delivery to the liver and inflammatory joints, and to localized siRNA delivery to the ocular sphere.

Publication types

  • Review

MeSH terms

  • Animals
  • Clinical Trials as Topic
  • Humans
  • Nanoparticles / adverse effects
  • Nanoparticles / chemistry*
  • RNA, Small Interfering / administration & dosage*
  • RNA, Small Interfering / therapeutic use
  • RNAi Therapeutics / adverse effects
  • RNAi Therapeutics / methods*


  • RNA, Small Interfering