Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 89 (1), 89-93

Expression of Human Alpha 1-antitrypsin in Dogs After Autologous Transplantation of Retroviral Transduced Hepatocytes

Affiliations

Expression of Human Alpha 1-antitrypsin in Dogs After Autologous Transplantation of Retroviral Transduced Hepatocytes

M A Kay et al. Proc Natl Acad Sci U S A.

Abstract

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 10(9) 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 alpha 1-antitrypsin cDNA under transcriptional control of the cytomegalovirus promoter. Both animals had significant human alpha 1-antitrypsin in the serum for 1 month. Although the serum levels of human alpha 1-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.

Similar articles

See all similar articles

Cited by 43 PubMed Central articles

See all "Cited by" articles

References

    1. Hum Gene Ther. 1990 Summer;1(2):135-49 - PubMed
    1. Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4626-30 - PubMed
    1. Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1217-21 - PubMed
    1. Hepatology. 1991 Jul;14(1):144-9 - PubMed
    1. Proc Natl Acad Sci U S A. 1990 Nov;87(21):8437-41 - PubMed

Publication types

LinkOut - more resources

Feedback