Cellular immunity to viral antigens limits E1-deleted adenoviruses for gene therapy.

Published

Journal Article

An important limitation that has emerged in the use of adenoviruses for gene therapy has been loss of recombinant gene expression that occurs concurrent with the development of pathology in the organ expressing the transgene. We have used liver-directed approaches to gene therapy in mice to study mechanisms that underlie the problems with transient expression and pathology that have characterized in vivo applications of first-generation recombinant adenoviruses (i.e., those deleted of E1a and E1b). Our data are consistent with the following hypothesis. Cells harboring the recombinant viral genome express the transgene as desired; however, low-level expression of viral genes also occurs. A virus-specific cellular immune response is stimulated that leads to destruction of the genetically modified hepatocytes, massive hepatitis, and repopulation of the liver with nontransgene-containing hepatocytes. These findings suggest approaches for improving recombinant adenoviruses that are based on further crippling the virus to limit expression of nondeleted viral genes.

Full Text

Duke Authors

Cited Authors

  • Yang, Y; Nunes, FA; Berencsi, K; Furth, EE; Gönczöl, E; Wilson, JM

Published Date

  • May 10, 1994

Published In

Volume / Issue

  • 91 / 10

Start / End Page

  • 4407 - 4411

PubMed ID

  • 8183921

Pubmed Central ID

  • 8183921

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.91.10.4407

Language

  • eng

Conference Location

  • United States