title: A new surgical approach to improve gene transfer in liver using lentiviral vectors.
abstract: OBJECTIVE
  Metabolic inherited liver diseases are attractive targets for gene therapy. Recombinant lentiviruses are very powerful viral vectors able to infect nonmitotic cells. We wanted to develop a new surgical approach to improve gene transfer in adult liver using low viral doses.
  
  
  METHODS
  Adult rats were injected with 2.108 infectious particles of lentiviral vectors encoding the green fluorescent protein marker gene under control of a liver-specific promoter transthyretin. In the control group (n = 5), gene delivery was performed by inflow intraportal injection. In the surgical group (n = 5), liver was completely excluded from systemic circulation before viral injection in infrahepatic vena cava with high pressure.
  
  
  RESULTS
  At day 9, transduction efficiency was 14.35% in the surgical group 3 and 0.39% in the control group (P = .016). At month 2, the number of transduced hepatocytes decreased in the most part of rats, except in half of rats in the surgical group. Antibodies against green fluorescent protein were detected in all rats at month 2, except one in the surgical group.
  
  
  CONCLUSIONS
  We developed a new surgical approach allowing an efficient transduction of hepatocytes in adult rats using lentivirus at low viral doses. We have now to control the immune response to permit long-term expression of transgene.
authors.affiliation: Pediatric Surgery Department, University Hospital, 44093 Nantes, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Dariel
authors.forename: Tuan Huy
authors.initials: TH
authors.lastname: Nguyen
authors.forename: Virginie
authors.initials: V
authors.lastname: Pichard
authors.forename: Françoise
authors.initials: F
authors.lastname: Schmitt
authors.forename: Dominique
authors.initials: D
authors.lastname: Aubert
authors.forename: Nicolas
authors.initials: N
authors.lastname: Ferry
authors.forename: Guillaume
authors.initials: G
authors.lastname: Podevin
mesh_terms: D000818:Animals; D002452:Cell Count; D002478:Cells, Cultured; D005260:Female; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000235:genetics; D022781:Hepatocytes / Q000378:metabolism; D007150:Immunohistochemistry; D016086:Lentivirus / Q000235:genetics*; D008099:Liver / Q000098:blood supply; D008102:Liver Circulation; D008297:Male; D010957:Plasmids; D051381:Rats; D011911:Rats, Gunn; D014161:Transduction, Genetic; D014684:Venae Cavae
chemical_list: D049452:Green Fluorescent Proteins