en
Scientific article
English

Highly efficient lentiviral vector-mediated transduction of nondividing, fully reimplantable primary hepatocytes

Published inMolecular therapy, vol. 6, no. 2, p. 199-209
Publication date2002
Abstract

Gene therapy is an attractive approach for the treatment of liver disease. We demonstrate that a so-called third-generation human immunodeficiency virus (HIV)-derived vector system can govern the efficient delivery, integration, and stable expression of a transgene into primary human hepatocytes in the complete absence of cell division. We also show that rodent hepatocytes exhibit a significant degree of resistance to HIV vector-mediated transduction, a phenotype that is particularly pronounced in murine hepatocytes and that results from a block in the immediate-early phase of infection. We finally describe a methodology, that allows very high rates of transduction through minimal in vitro manipulation, in which hepatocytes are kept in suspension and reimplanted within a few hours of harvest with a fully preserved engraftment potential. These results have immediate implications for the treatment of liver diseases by the transplantation of genetically modified hepatocytes, an approach that could be applied to a number of hereditary and acquired hepatic disorders.

Keywords
  • Animals
  • Cell Division
  • Cell Line
  • Gene Transfer Techniques
  • Genetic Therapy/methods
  • Genetic Vectors
  • HIV/genetics
  • HeLa Cells
  • Hepatocytes/cytology/transplantation
  • Humans
  • Lentivirus/genetics
  • Liver Diseases/therapy
  • Male
  • Mice
  • Rats
  • Rats, Sprague-Dawley
  • Transduction, Genetic
Citation (ISO format)
NGUYEN, Tuan Huy et al. Highly efficient lentiviral vector-mediated transduction of nondividing, fully reimplantable primary hepatocytes. In: Molecular therapy, 2002, vol. 6, n° 2, p. 199–209. doi: 10.1006/mthe.2002.0653
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Article (Published version)
accessLevelRestricted
Identifiers
ISSN of the journal1525-0016
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