Cellular immunity to viral antigens limits E1-deleted adenoviruses for gene therapy - PubMed (original) (raw)
Comparative Study
Cellular immunity to viral antigens limits E1-deleted adenoviruses for gene therapy
Y Yang et al. Proc Natl Acad Sci U S A. 1994.
Abstract
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.
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References
- J Gen Virol. 1977 Jul;36(1):59-74 - PubMed
- Hum Gene Ther. 1993 Dec;4(6):771-80 - PubMed
- Virology. 1983 Jul 30;128(2):480-4 - PubMed
- Mol Cell Biol. 1984 May;4(5):867-74 - PubMed
- Anal Biochem. 1987 Apr;162(1):156-9 - PubMed
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