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

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

Author information

1
Gene Therapy Center, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
2
Department of Genetics, Stanford University School of Medicine, Stanford, California, USA.
3
1] Gene Therapy Center, University of Massachusetts Medical School, Worcester, Massachusetts, USA [2] Department of Pediatrics, University of Massachusetts Medical School, Worcester, Massachusetts, USA.

Abstract

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.

PMID:
24352214
PMCID:
PMC3982504
DOI:
10.1038/mt.2013.285
[Indexed for MEDLINE]
Free PMC Article

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