Recombinant AAV as a platform for translating the therapeutic potential of RNA interference

Mol Ther. 2014 Apr;22(4):692-701. doi: 10.1038/mt.2013.285. Epub 2013 Dec 19.


RNA interference has become a ubiquitous biological tool, and is being harnessed for therapeutic purposes as well. Therapeutic posttranscriptional gene silencing takes advantage of the endogenous RNAi pathway through delivery of either chemically synthesized siRNAs, or transgenes expressing hairpin-based inhibitory RNAs (e.g., shRNAs and artificial miRNAs). RNAi has expanded the field of viral gene therapy from gene replacement to gene knockdown. Here, we review various noncoding RNAs such as shRNAs, miRNAs, and miRNA decoys which can be utilized for therapeutic applications when expressed from recombinant adeno-associated vectors (AAV), and present examples of their basic design. In addition the basis of exploiting cellular miRNA profiles for detargeting AAV expression from specific cells is described. Finally, an overview of AAV-mediated RNAi preclinical studies is presented, and current RNAi-based clinical trials are reviewed.

Publication types

  • Review

MeSH terms

  • Dependovirus / genetics
  • Gene Expression Regulation
  • Gene Silencing
  • Genetic Therapy*
  • Genetic Vectors
  • Humans
  • MicroRNAs / genetics*
  • RNA Interference*
  • RNA, Small Interfering / genetics*


  • MicroRNAs
  • RNA, Small Interfering