Adenovirus-mediated gene transfer into rat cardiac allografts. Comparison of direct injection and perfusion.

Published

Journal Article

With the ultimate goal of modulating the host immune response in organ transplantation, gene therapy studies have demonstrated that direct plasmid DNA injection into transplanted myocardium can result in detectable levels of transgene expression. However, the restricted distribution and low level of transgene expression evident in these studies have limited its application. Recently, replication-defective adenovirus vectors have been shown to be an efficient gene-transfer vehicle in vivo whose infection does not require target-cell proliferation. In the present study, adenovirus vectors encoding reporter genes were delivered into transplanted hearts by either direct injection into the myocardium or perfusion via aorta of the donor hearts. The efficacy and stability of the transgene expression by perfusion and by direct injection were examined and compared. Using the adenovirus vector encoding the firefly luciferase gene, we found that a higher level of transgene expression was achieved by direct injection, but that more evenly distributed transgene expression was observed in hearts perfused with viral vector. These results were further confirmed by 5-bromo-4-chloro-3-indolyl-beta-d-galactoside histochemical staining of another adenoviral vector encoding beta-galactosidase. The transgene expression was not stable and decreased within 1 month with either delivery method. Nevertheless, these results indicate that adenovirus-mediated gene transfer can result in short-term expression of the gene throughout the heart and may be useful as a gene vector in organ transplantation.

Full Text

Duke Authors

Cited Authors

  • Wang, J; Ma, Y; Knechtle, SJ

Published Date

  • June 27, 1996

Published In

Volume / Issue

  • 61 / 12

Start / End Page

  • 1726 - 1729

PubMed ID

  • 8685951

Pubmed Central ID

  • 8685951

International Standard Serial Number (ISSN)

  • 0041-1337

Digital Object Identifier (DOI)

  • 10.1097/00007890-199606270-00011

Language

  • eng

Conference Location

  • United States