Hepatocyte-based gene therapy

Chandan Guha, Namita Roy-Chowdhury, Hugo Jauregui, Jayanta Roy-Chowdhury

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Hepatocyte-based gene therapy may be used to replace a missing gene product, confer proliferating ability to cultured hepatocytes, prevent allograft rejection, massively repopulate the host liver, or grow xenogeneic hepatocytes in mammalian liver. Gene transfer into isolated hepatocytes can be accomplished via nonviral or viral vectors, the viral vectors being more useful at this time. Common recombinant viruses that integrate into the host genome include murine leukemia retroviruses and lentiviruses, adenoassociated virus, and the T-antigen-deleted SV40 virus. Episomal viruses, such as adenoviruses, permit efficient gene transfer, but the transgene is lost upon proliferation of the transplanted hepatocyte in the host. Hybrid viruses that combine the high transduction efficiency of adenoviral vectors and the integrative capacity of other vectors, such as adenoassociated viruses, have been designed. Massive repopulation of the liver by transplanted hepatocytes can be achieved if a mitotic stimulus to the transplanted cells is combined with prevention of proliferation of the host hepatocytes. Treatment with a plant alkaloid or retrorsine, or preparative irradiation of the liver can be used to inhibit host hepatocellular proliferation, while partial hepatectomy, expression of Fas ligand, or thyroid hormone administration can be used as a mitotic stimulus to the transplanted cells.

Original languageEnglish (US)
Pages (from-to)51-57
Number of pages7
JournalJournal of Hepato-Biliary-Pancreatic Surgery
Volume8
Issue number1
DOIs
StatePublished - 2001

Fingerprint

Genetic Therapy
Hepatocytes
Viruses
Liver
Genes
Lentivirus
Fas Ligand Protein
Simian virus 40
Viral Tumor Antigens
Hepatectomy
Retroviridae
Transgenes
Thyroid Hormones
Alkaloids
Adenoviridae
Allografts
Leukemia
Genome

Keywords

  • Gene therapy
  • Hepatocyle transplantation
  • Immortalization of hepatocytes
  • Liver diseases
  • Nonviral
  • Vectors
  • Viral

ASJC Scopus subject areas

  • Surgery

Cite this

Hepatocyte-based gene therapy. / Guha, Chandan; Roy-Chowdhury, Namita; Jauregui, Hugo; Roy-Chowdhury, Jayanta.

In: Journal of Hepato-Biliary-Pancreatic Surgery, Vol. 8, No. 1, 2001, p. 51-57.

Research output: Contribution to journalArticle

Guha, Chandan ; Roy-Chowdhury, Namita ; Jauregui, Hugo ; Roy-Chowdhury, Jayanta. / Hepatocyte-based gene therapy. In: Journal of Hepato-Biliary-Pancreatic Surgery. 2001 ; Vol. 8, No. 1. pp. 51-57.
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