Lentiviral vector-mediated RNA silencing in the central nervous system

Hum Gene Ther Methods. 2014 Feb;25(1):14-32. doi: 10.1089/hgtb.2013.016. Epub 2013 Nov 1.


RNA silencing is an established method for investigating gene function and has attracted particular interest because of the potential for generating RNA-based therapeutics. Using lentiviral vectors as an efficient delivery system that offers stable, long-term expression in postmitotic cells further enhances the applicability of an RNA-based gene therapy for the CNS. In this review we provide an overview of both lentiviral vectors and RNA silencing along with design considerations for generating lentiviral vectors capable of RNA silencing. We go on to describe the current preclinical data regarding lentiviral vector-mediated RNA silencing for CNS disorders and discuss the concerns of side effects associated with lentiviral vectors and small interfering RNAs and how these might be mitigated.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Central Nervous System Diseases / genetics*
  • Central Nervous System Diseases / metabolism*
  • Central Nervous System Diseases / pathology
  • Genetic Vectors / chemistry
  • Genetic Vectors / genetics
  • Genetic Vectors / metabolism*
  • Humans
  • Lentivirus / genetics*
  • RNA Interference*
  • RNA, Small Interfering / metabolism


  • RNA, Small Interfering