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.
Similar content being viewed by others
References
Horwich, A.L. Curr. Topics Micro. Immunol. 168, 186–200 (1991).
Friedmann, T. Science 244, 1275–1281 (1989).
Wilson, J.M. and Chowdhury, J.R. Molec. biol. Med. 7, 223–232 (1990).
Miller, A.D. Blood 76, 271–278 (1990).
Ledley, F.D. J. Inher. metab. Dis. 13, 597–616 (1990).
Nicolau, C., Le Pape, A., Soriano, P., Fargette, F. & Juhel, M.-F. Proc. natn. Acad. Sci. U.S.A. 80, 1068–1072 (1983).
Soriano, P. et al. Proc. natn. Acad. Sci. U.S.A. 80, 7128–7131 (1983).
Kaneda, Y., Iwai, K. & Uchida, T. Science 243, 375–378 (1989).
Kaneda, Y., Iwai, K. & Uchida, T. J. biol. Chem. 264, 12126–12129 (1989).
Kato, K., Nakanishi, M., Kaneda, Y., Uchida, T. & Okada, Y. J. biol. Chem. 266, 3361–3364 (1991).
Wu, C.H., Wilson, J.M. & Wu, G.Y. J. biol. Chem. 264, 16985–16987 (1989).
Wu, G.Y. et al. J. biol. Chem. 266, 14338–14342 (1991).
Wilson, J.M. et al. J. biol. Chem. 267, 963–967 (1992).
Hatzoglou, M. et al. J. biol. Chem. 265, 17285–17293 (1990).
Kaleko, M., Garcia, J.V. & Miller, A.D. Hum. Gene Ther. 2, 27–32 (1991).
Demetriou, A.A. et al. Science 233, 1190–1192 (1986).
Ponder, K.P. et al. Proc. natn. Acad. Sci. U.S.A. 88, 1217–1221 (1991).
Kay, M.A. et al. Proc. natn. Acad. Sci. U.S.A. 89, 89–93 (1992).
Inagaki, M. & Ogawa, K. Cell Struct. Funct. 16, 283–288 (1991).
Wilson, J.M. et al. Proc. natn. Acad. Sci. U.S.A. 87, 8437–8441 (1990).
Chowdhury, J.R. et al. Science 254, 1802–1805 (1991).
Berkner, K.L. Biotechniques 6, 616–628 (1988).
Horwitz, M.S. Virology 2nd edn (eds Fields, B. N. & Knipe, D.M.) 1679–1721 (Raven Press, New York, 1990).
Rosenfeld, M.A. et al. Science 252, 431–434 (1991).
Rosenfeld, M.A. et al. Cell 68, 143–155 (1992).
Straus, S.E. in The Adenoviruses (ed Ginsberg, H. S.) 451–496 (Plenum Press, New York & London, 1984).
Griffiths, P.D., Ellis, D.S. & Zukerman, A.J. Brit. Med. Bull. 46, 512–532 (1990).
Allan, F.D. Essentials of Human Embryology (ed Allan, F. D.) 93–99 (Oxford University Press, New York, 1960).
Stratford-Perricaudet, L.D., Levrero, M., Chasse, J.-F., Perricaudet, M. & Briand, P. Hum. Gene Ther. 1, 241–256 (1990).
Chanock, R.M., Ludwig, W., Heubner, R.J., Cate, T.R. & Chu, L.-W. JAMA 195, 445–452 (1966).
Garver,Jr.,R.I., Chytil, A., Courtney, M. & Crystal, R.G., Science 237, 762–764 (1987).
Gilardi, P., Courtney, M., Pavirani, A. & Perricaudet, M. FEBS Lett. 267, 60–62 (1990).
Casolaro, M.A. et al. J. appl. Physiol. 63, 2015–2023 (1987).
Elbein, A.D., Ann. Rev. Biochem. 56, 497–534 (1987).
Curiel, D.T., Chytil, A., Courtney, M. & Crystal, R.G. J. biol. Chem. 264, 10477–10486 (1989).
Pearson, B., Wolf, P.L. & Vazquez, J., Lab. Invest. 12, 1249–1259 (1963).
Seglen, P.O. J. Toxicol. Environ. Health 5, 551–560 (1979).
French, T. in The Clinical Chemistry of Laboratory Animals 1st edn(eds Loeb, W. F. & Quimby, F. W.) 213, (Pergamon Press, New York, 1989).
Lonberg-Holm, K. & Philipson, L.J. J. Virol. 4, 323–338 (1969).
Philipson, L., Lonberg-Holm, K. & Pettersson, U. J. Virol. 2, 1064–1075 (1968).
Pastan, I., Seth, P., FitzGerald, D. & Willingham, M. in Concepts in Viral Pathogenesis II (eds Notkins, A.L. & Oldstone, M.B.A.) 141–146 (Springer-Verlag, New York, 1986).
Stratford-Perricaudet, L.D., Makeh, I., Perricaudet, M. & Briand, P.J. J. clin. Invest. 90, 626–630 (1992).
Jones, S.N. et al. J. biol. Chem. 265, 14684–14690 (1990).
Shimada, T. et al. FEBS Lett. 279, 198–200 (1991).
Seglen, P.O., Exptl. Cell. Res. 82, 391–398 (1973).
Graham, F.L., Smiley, J., Russell, W.C. & Nairn, R.J. J. gen. Virol. 36, 59–74 (1977).
Vehar, G.A., Lawn, R.M., Tuddenham, E.G.D. & Wood, W.I. in The Metabolic Basis of Inherited Disease 6th edn(eds Scriver, C.R., Beaudet, A.L, Sly, W.S. & Valle, D.) 2107–2122, 2155–2182, (McGraw-Hill, New York, 1989).
Brusilow, S.W. & Horwich, A.L. in The Metabolic Basis of Inherited Disease 6th edn(eds Scriver, C. R., Beaudet, A.L, Sly, W.S. & Valle, D.) 399–491, 495–774, 1305–1408 (McGraw-Hill, New York, 1989).
Goldstein, J.L. & Brown, M.S. in The Metabolic Basis of Inherited Disease 6th edn(eds Scriver, C. R., Beaudet, A.L, Sly, W.S. & Valle, D.) 1215–1250 (McGraw-Hill, New York, 1989).
Arn, P.H. et al. New Engl. J. Med. 322, 1652–1655 (1990).
Brues, A.M. & Marble, B.B. J. exp. Med. 65, 15–27 (1937).
Palmer, T.D., Rosman, G.J., Osborne, W.R.A. & Miller, A.D. Proc. natn. Acad. Sci. U.S.A. 88, 1330–1334 (1991).
Graham, F.L. & Van Der Eb, A.J. Virology 52, 456–467 (1973).
Yamamoto, T., de Crombrugghe, B., & Pastan, I. Cell 22, 787–797 (1980).
Kalderon, D., Roberts, B.L., Richardson, W.D. & Smith, A.E. Cell 39, 499–509 (1984).
Price, J., Turner, D. & Cepko, C. Proc. natn. Acad. Sci. U.S.A. 84, 156–160 (1987).
Jones, N. & Shenk, T. Cell 17, 683–689 (1979).
Harper, M.E., Marselle, L.M., Gallo, R.C. & Wong-Staal, F. Proc. natn. Acad. Sci. U.S.A. 83, 772–776 (1986).
Bernaudin, J.-F. et al. J. Immunol. 140, 3822–3829 (1988).
Dannenberg, Jr., A.M. & Suga, M. in Methods for Studying Mononuclear Phagocytes (eds Adams, D.O., Edelson P.J. & Koren, H.S.) 375–395 (Academic Press, New York, 1981).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/ng0892-372
- Springer Nature America, Inc.
This article is cited by
-
Adenoviral vectors for cardiovascular gene therapy applications: a clinical and industry perspective
Journal of Molecular Medicine (2022)
-
Suppression of PPARγ-mediated monoacylglycerol O-acyltransferase 1 expression ameliorates alcoholic hepatic steatosis
Scientific Reports (2016)
-
Alpha-1 Antitrypsin Deficiency: New Developments in Augmentation and Other Therapies
BioDrugs (2013)
-
Long-term effects of hepatocyte growth factor gene therapy in rat myocardial infarct model
Gene Therapy (2012)
-
Coagulation factor X mediates adenovirus type 5 liver gene transfer in non-human primates (Microcebus murinus)
Gene Therapy (2012)