UNIGE document Scientific Article
previous document  unige:19682  next document
add to browser collection
Title

A step toward liver gene therapy: efficient correction of the genetic defect of hepatocytes isolated from a patient with Crigler-Najjar syndrome type 1 with lentiviral vectors

Authors
Birraux, Jacques
Published in Transplantation. 2009, vol. 87, no. 7, p. 1006-1012
Abstract BACKGROUND: Ex vivo liver gene therapy may be a future alternative to orthotopic liver transplantation for the treatment of some liver diseases. We previously described the transduction in suspension with lentiviral vectors and immediate hepatocyte transplantation (SLIT) protocol and its high transduction rate with normal human hepatocytes. We also reported SLIT efficiency in the animal model of Crigler-Najjar type 1 syndrome (CN-1), the Gunn rat. Here, we evaluated SLIT efficiency with diseased human hepatocytes. METHODS: Hepatocytes of the liver from a 4-year-old patient presenting CN-1 were isolated. They were transduced with liver-specific lentiviral vectors expressing uridine-diphosphate-glucuronosyltransferase (hUGT1A1) or green fluorescent protein, and then analyzed in vitro for transduction efficiency and hUGT1A1 expression, or transplanted in nonobese diabetic/severe combined immunodeficiency (SCID) mice to evaluate long-term survival of transplanted cells. RESULTS: More than 90% of CN-1 hepatocytes were transduced. Hepatocytes produced hUGT1A1 protein after lentiviral transduction. After having been subjected to the SLIT, lentivirally transduced CN-1 hepatocytes engrafted long term (up to 26 weeks posttransplantation) in recipient livers and expressed green fluorescent protein or hUGT1A1 vector. CONCLUSION: The SLIT protocol allowed for a high transduction of CN-1 hepatocytes and restoration of the expression of the deficient protein. Furthermore, long-term survival of lentivirally transduced CN-1 hepatocytes in the liver of immunodeficient mice was demonstrated. This study is therefore an important step toward human application of lentiviral gene therapy.
Keywords AnimalsChild, PreschoolCrigler-Najjar Syndrome/*geneticsCryopreservation/methodsFemale*Gene TherapyGenetic VectorsGlucuronosyltransferase/*geneticsHepatectomyHepatocytes/cytology/*physiology/*transplantationHumansLentivirus/*geneticsMiceMice, Inbred NODMice, SCID
Identifiers
PMID: 19352119
Full text
Article - document accessible for UNIGE members only Limited access to UNIGE
Structures
Research group Groupe Wildhaber Barbara (chirurgie pédiatrique) (886)
Citation
(ISO format)
BIRRAUX, Jacques et al. A step toward liver gene therapy: efficient correction of the genetic defect of hepatocytes isolated from a patient with Crigler-Najjar syndrome type 1 with lentiviral vectors. In: Transplantation, 2009, vol. 87, n° 7, p. 1006-1012. https://archive-ouverte.unige.ch/unige:19682

247 hits

0 download

Update

Deposited on : 2012-04-23

Export document
Format :
Citation style :