In vivo retrovirus-mediated gene transfer to the liver of dogs results in transient expression and induction of a cytotoxic immune response

Hum Gene Ther. 1999 Dec 10;10(18):2917-25. doi: 10.1089/10430349950016339.


Gene transfer in regenerating dog liver using high-titer recombinant retroviral vectors carrying the E. coli beta-galactosidase gene was studied. Supernatants containing amphotropic or gibbon ape pseudotyped recombinant retroviruses were infused into a peripheral vein in beagle dogs after partial hepatectomy. The kinetics of liver regeneration were determined in the animals and daily infusions were carried out for 4 or 5 days during the regeneration period. Up to 2.8% of hepatocytes were beta-galactosidase positive at the end of the procedure. However, the number of positive cells declined rapidly and few positive hepatocytes were detected after 3 weeks. PCR demonstrated the disappearance of the provirus. Histologically, inflammatory lesions were observed in the transduced livers. Finally, we demonstrated the presence of a cytotoxic T lymphocyte immune response directed against beta-galactosidase-expressing cells, which could explain the disappearance of the transgene. This work suggests that the efficiency of in vivo gene delivery using high-titer retroviral vectors directly infused into the circulation may be hampered by a cytotoxic immune response against the infected cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cytotoxicity, Immunologic / genetics*
  • DNA Primers
  • Dogs
  • Escherichia coli / genetics
  • Female
  • Gene Transfer Techniques*
  • Liver / enzymology*
  • Liver Regeneration / genetics
  • Retroviridae / genetics*
  • T-Lymphocytes, Cytotoxic / immunology
  • Transduction, Genetic
  • beta-Galactosidase / genetics


  • DNA Primers
  • beta-Galactosidase