Potential for germ line transmission after intramyocardial gene delivery by adeno-associated virus.

Journal Article (Journal Article)

Intramyocardial injection of adeno-associated virus (AAV) has been shown to be an effective strategy for cardiac gene delivery. This approach leads to long-term gene expression in the heart, offering the possibility of chronic gene therapy. However, the long-term safety of this approach with regard to vector bio-distribution and extracardiac transgene expression has not been evaluated. To examine these issues, 8-week-old male Sprague-Dawley rats were injected intramyocardially with either 4x10(11) particles of AAV-2-lacZ or saline at five locations in the anterioposterior apical region of the left ventricle. Animals were sacrificed at 3 and 6 months after gene transfer, tissues were harvested and analyzed for lacZ expression by semi-quantitative RT-PCR and beta-galactosidase activity using X-gal staining. We observed high level of transgene expression in the myocardium at 3 months after gene transfer, which persisted up to 6 months of follow-up. Also, significantly we detected lacZ expression and beta-galactosidase activity in extracardiac tissues such as liver, kidney, and testes at 6 months. More significantly, late transgene expression was detected in cellular elements of the seminiferous tubule, including Sertoli cells and spermatogonia like cells. These data demonstrate the efficacy of AAV-2 delivery for long-term myocardial gene therapy, but raise concerns about the possibility of ectopic transgene expression and germ cell line infection.

Full Text

Duke Authors

Cited Authors

  • Pachori, AS; Melo, LG; Zhang, L; Loda, M; Pratt, RE; Dzau, VJ

Published Date

  • January 16, 2004

Published In

Volume / Issue

  • 313 / 3

Start / End Page

  • 528 - 533

PubMed ID

  • 14697221

International Standard Serial Number (ISSN)

  • 0006-291X

Digital Object Identifier (DOI)

  • 10.1016/j.bbrc.2003.11.140


  • eng

Conference Location

  • United States