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Title

Highly efficient lentiviral vector-mediated transduction of nondividing, fully reimplantable primary hepatocytes
Authors
Nguyen, Tuan Huy
Oberholzer, José
Birraux, Jacques Maurice
Majno, Pietro
Morel, Philippe
Trono, Didier
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 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
Identifiers
PMID: 12161186
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Article (Published version) (369 Kb) - document accessible for UNIGE members only Limited access to UNIGE
Other version: http://www.nature.com/mt/journal/v6/n2/abs/mt2002158a.html
Structures
Faculté de médecine / Section de médecine clinique / Département de chirurgie
Research groups Hépatologie chirurgicale (327)
Chirurgie viscérale (104)
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. https://archive-ouverte.unige.ch/unige:38192

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Deposited on : 2014-06-26

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