Expression of human α1-antitrypsin in dogs after autologous transplantation of retroviral transduced hepatocytes

M. A. Kay, P. Baley, S. Rothenberg, F. Leland, L. Fleming, K. P. Ponder, T. J. Liu -, M. Finegold, G. Darlington, W. Pokorny, S. L.C. Woo

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214 Scopus citations


The liver represents an excellent organ for gene therapy since many genetic disorders result from the deficiency of liver-specific gene products. We have previously demonstrated that transgenic mouse hepatocytes can be heterologously transplanted into congenic recipients where they survived indefinitely and continued to function as hepatocytes. Here we demonstrate the autologous transplantation of retrovirally transduced canine hepatocytes. At least 1 x 109 hepatocytes or 5% of the liver mass can be transplanted by the portal vasculature. In two animals we have transplanted hepatocytes transduced with a retroviral vector containing the human α1-antitrypsin cDNA under transcriptional control of the cytomegalovirus promoter. Both animals had significant human α1-antitrypsin in the serum for 1 month. Although the serum levels of human α1-antitrypsin eventually fell due to inactivation of the cytomegalovirus promoter, PCR analysis demonstrated that a significant fraction of transduced hepatocytes migrated to the liver and continued to survive in vivo. The results suggest that gene therapy of hepatic deficiencies may be achieved by hepatocellular transplantation after genetic reconstitution with the use of promoters of cellular genes that are active in the normal liver.

Original languageEnglish
Pages (from-to)89-93
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number1
StatePublished - 1992


  • autologous transplantation
  • canine hepatocyte
  • cytomegalovirus promoter
  • gene therapy


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