Recombinant adeno-associated virus for muscle directed gene therapy.


Journal Article

Although gene transfer with adeno-associated virus (AAV) vectors has typically been low, transduction can be enhanced in the presence of adenovirus gene products through the formation of double stranded, non-integrated AAV genomes. We describe the unexpected finding of high level and stable transgene expression in mice following intramuscular injection of purified recombinant AAV (rAAV). The rAAV genome is efficiently incorporated into nuclei of differentiated muscle fibers where it persists as head-to-tail concatamers. Fluorescent in situ hybridization of muscle tissue suggests single integration sites. Neutralizing antibody against AAV capsid proteins does not prevent readministration of vector. Remarkably, no humoral or cellular immune responses are elicited to the neoantigenic transgene product E. coli beta-galactosidase. The favorable biology of rAAV in muscle-directed gene therapy described in this study expands the potential of this vector for the treatment of inherited and acquired diseases.

Full Text

Cited Authors

  • Fisher, KJ; Jooss, K; Alston, J; Yang, Y; Haecker, SE; High, K; Pathak, R; Raper, SE; Wilson, JM

Published Date

  • March 1997

Published In

Volume / Issue

  • 3 / 3

Start / End Page

  • 306 - 312

PubMed ID

  • 9055858

Pubmed Central ID

  • 9055858

Electronic International Standard Serial Number (EISSN)

  • 1546-170X

International Standard Serial Number (ISSN)

  • 1078-8956

Digital Object Identifier (DOI)

  • 10.1038/nm0397-306


  • eng