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

Published in Molecular therapy. 2002, vol. 6, no. 2, p. 199-209
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 AnimalsCell DivisionCell LineGene Transfer TechniquesGenetic Therapy/methodsGenetic VectorsHIV/geneticsHeLa CellsHepatocytes/cytology/transplantationHumansLentivirus/geneticsLiver Diseases/therapyMaleMiceRatsRats, Sprague-DawleyTransduction, Genetic
PMID: 12161186
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Research groups Chirurgie viscérale (104)
Chirurgie viscérale (HUG)
Hépatologie chirurgicale (327)
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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 https://archive-ouverte.unige.ch/unige:38192

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Deposited on : 2014-06-26

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