Lentiviral delivery of short hairpin RNAs

Adv Drug Deliv Rev. 2009 Jul 25;61(9):732-45. doi: 10.1016/j.addr.2009.03.004. Epub 2009 Mar 31.


In less than a decade after discovery, RNA interference-mediated gene silencing is already being tested as potential therapy in clinical trials for a number of diseases. Lentiviral vectors provide a means to express short hairpin RNA (shRNA) to induce stable and long-term gene silencing in both dividing and non-dividing cells and thus, are being intensively investigated for this purpose. However, induction of long-term shRNA expression can also cause toxicities by inducing off-target effects and interference with the endogenous micro-RNA (miRNA) pathway that regulates cellular gene expression. Recently, several advances have been made in the shRNA vector design to mimic cellular miRNA processing and to express multiplex siRNAs in a tightly regulated and reversible manner to overcome toxicities. In this review we describe some of these advances, focusing on the progress made in the development of lentiviral shRNA delivery strategies to combat viral infections.

Publication types

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

MeSH terms

  • Gene Transfer Techniques*
  • Genetic Vectors / genetics
  • HIV-1 / genetics
  • Hepatitis Viruses / genetics
  • Lentivirus / genetics*
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics
  • RNA Interference
  • RNA, Small Interfering / genetics*
  • Virus Assembly


  • MicroRNAs
  • RNA, Small Interfering