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

H. A. Jaffe, C. Danel, G. Longenecker, M. Metzger, Y. Setoguchi, M. A. Rosenfeld, T. W. Gant, S. S. Thorgeirsson, L. D. Stratford-Perricaudet, M. Perricaudet, A. Pavirani, J. P. Lecocq, Ronald Crystal

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)372-378
Number of pages7
JournalNature Genetics
Volume1
Issue number5
DOIs
Publication statusPublished - 1 Jan 1992
Externally publishedYes

Fingerprint

Adenoviridae
Gene Expression
Hepatocytes
Liver
Genetic Therapy
Galactosidases
Lac Operon
Complementary DNA
Escherichia coli
Infection
Serum

ASJC Scopus subject areas

  • Genetics

Cite this

Jaffe, H. A., Danel, C., Longenecker, G., Metzger, M., Setoguchi, Y., Rosenfeld, M. A., ... Crystal, R. (1992). Adenovirus–mediated in vivo gene transfer and expression in normal rat liver. Nature Genetics, 1(5), 372-378. https://doi.org/10.1038/ng0892-372

Adenovirus–mediated in vivo gene transfer and expression in normal rat liver. / Jaffe, H. A.; Danel, C.; Longenecker, G.; Metzger, M.; Setoguchi, Y.; Rosenfeld, M. A.; Gant, T. W.; Thorgeirsson, S. S.; Stratford-Perricaudet, L. D.; Perricaudet, M.; Pavirani, A.; Lecocq, J. P.; Crystal, Ronald.

In: Nature Genetics, Vol. 1, No. 5, 01.01.1992, p. 372-378.

Research output: Contribution to journalArticle

Jaffe, HA, Danel, C, Longenecker, G, Metzger, M, Setoguchi, Y, Rosenfeld, MA, Gant, TW, Thorgeirsson, SS, Stratford-Perricaudet, LD, Perricaudet, M, Pavirani, A, Lecocq, JP & Crystal, R 1992, 'Adenovirus–mediated in vivo gene transfer and expression in normal rat liver', Nature Genetics, vol. 1, no. 5, pp. 372-378. https://doi.org/10.1038/ng0892-372
Jaffe HA, Danel C, Longenecker G, Metzger M, Setoguchi Y, Rosenfeld MA et al. Adenovirus–mediated in vivo gene transfer and expression in normal rat liver. Nature Genetics. 1992 Jan 1;1(5):372-378. https://doi.org/10.1038/ng0892-372
Jaffe, H. A. ; Danel, C. ; Longenecker, G. ; Metzger, M. ; Setoguchi, Y. ; Rosenfeld, M. A. ; Gant, T. W. ; Thorgeirsson, S. S. ; Stratford-Perricaudet, L. D. ; Perricaudet, M. ; Pavirani, A. ; Lecocq, J. P. ; Crystal, Ronald. / Adenovirus–mediated in vivo gene transfer and expression in normal rat liver. In: Nature Genetics. 1992 ; Vol. 1, No. 5. pp. 372-378.
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