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Adenovirus–mediated in vivo gene transfer and expression in normal rat liver

Nature Genetics volume 1, pages 372–378 (1992)Cite this article

Abstract

Replication deficient, recombinant adenovirus (Ad) vectors do not require target cell replication for transfer and expression of exogenous genes and thus may be useful for in vivo gene therapy in hepatocytes. In vitro, primary cultures of rat hepatocytes infected with a recombinant Ad containing a human α1–antitrypsin cDNA (Ad–α1AT) synthesized and secreted human α1 AT for 4 weeks. In rats, in vivo intraportal administration of a recombinant Ad containing the E. coli lacZ gene, was followed by expression of β–galactosidase in hepatocytes 3 days after infection. Intraportal infusion of Ad–α1AT produced detectable serum levels of human α1AT for 4 weeks. Thus, targeted gene expression has been achieved in the liver, albeit at low levels, suggesting that adenovirus vectors may be a useful means for in vivo gene therapy in liver disorders.

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Authors and Affiliations

  1. Pulmonary Branch, National Heart, Lung, and Blood Institute, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, 20892, USA

    H. A. Jaffe, C. Danel, G. Longenecker, M. Metzger, Y. Setoguchi, M. A. Rosenfeld & R. G. Crystal

  2. Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, 20892, USA

    T. W. Gant & S. S. Thorgeirsson

  3. Institute Gustave Roussy, Centre National de la Recherche Scientifique Unité Associée 1301, 94805, Villejuif Cedex, France

    L. D. Stratford-Perricaudet & M. Perricaudet

  4. Transgene SA, 11 rue de Molsheim, 67082, Strasbourg, France

    A. Pavirani & J.-P. Lecocq

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  1. H. A. Jaffe
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  2. C. Danel
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Jaffe, H., Danel, C., Longenecker, G. et al. Adenovirus–mediated in vivo gene transfer and expression in normal rat liver. Nat Genet 1, 372–378 (1992). https://doi.org/10.1038/ng0892-372

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