Retroviral-mediated gene transfer into hepatocytes in vivo

Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8377-81. doi: 10.1073/pnas.88.19.8377.

Abstract

Stable gene transfer into hepatocytes might be used to compensate for a genetic deficiency affecting liver function or to deliver diffusible factors into the blood stream. In rats, we have combined retroviral-mediated gene transfer with a surgical procedure in which the liver is temporarily excluded from the circulation and infected in vivo. Partial hepatectomy was performed 24-48 hr before perfusion with virus to induce hepatocyte division and facilitate viral integration. A helper-free recombinant retrovirus coding for beta-galactosidase with nuclear localization was used to score cells that expressed the transgene. For at least 3 months after gene transfer, up to 5% of hepatocytes expressed nuclear beta-galactosidase. Whereas in vitro reimplantation of genetically modified hepatocytes has proved to be inefficient in stably transferring genes into the liver, our approach provides a feasible alternative.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cell Compartmentation
  • Gene Expression
  • Genetic Vectors
  • Leukemia Virus, Murine / genetics*
  • Liver / physiology*
  • Liver Regeneration
  • Molecular Sequence Data
  • Oligonucleotides / chemistry
  • Perfusion
  • Polymerase Chain Reaction
  • Rats
  • Rats, Inbred Lew
  • Recombinant Fusion Proteins
  • Regulatory Sequences, Nucleic Acid
  • Transfection*
  • beta-Galactosidase / genetics

Substances

  • Oligonucleotides
  • Recombinant Fusion Proteins
  • beta-Galactosidase