Skip to Main content Skip to Navigation
Journal articles

No tumour-initiating risk associated with scAAV transduction in newborn rat liver

Abstract : Delivery of recombinant adeno-associated virus (rAAV) vectors to the newborn liver is followed by a rapid loss of episomal vector copies because of hepatocyte proliferation. In selected hepatocytes, integration of rAAV genomes can lead to a sustained expression of the transgene. The safety of in vivo gene therapy with single-stranded AAV vectors has been questioned in a study reporting a high incidence of hepatocellular carcinoma, associated with provirus integration events in mice that receive an single-stranded AAV injection at birth. To investigate the tumour-initiating potential of the newly established self-complementary AAV (scAAV) vectors in the liver, groups of newborn rats received intravenous injection of a scAAV vector encoding the green fluorescent protein (GFP), or were injected with phosphate-buffered saline (PBS) or diethylnitrosamine (DEN), a well-known liver tumour initiator. The rats were fed on a diet containing 2-acetylaminofluorene, a potent liver tumour-promoting agent to accelerate the carcinogenic process. After 2 months, the animals were killed and their livers analysed. Preneoplastic nodules were identified by glutathion S-transferase-p (GSTp) staining, and GFP expression was detected by immunohistochemistry. Vector genome integration events were analysed. The numbers of GSTp-positive foci were comparable in the PBS and the scAAV-GFP groups and significantly higher in the DEN group. The proportion of GSTp-positive foci that also expressed GFP was low and in the range expected for random occurrence. No specific integration hot spots were detected by linear amplification-mediated-PCR in transduced liver. In conclusion, scAAV transduction of newborn rat liver does not trigger preneoplastic lesions suggesting an absence of liver tumourigenesis.
Document type :
Journal articles
Complete list of metadata

Cited literature [25 references]  Display  Hide  Download
Contributor : Sylvie Le Bihan Connect in order to contact the contributor
Submitted on : Wednesday, June 26, 2019 - 10:39:26 AM
Last modification on : Wednesday, April 27, 2022 - 3:46:26 AM


 Restricted access
To satisfy the distribution rights of the publisher, the document is embargoed until : jamais

Please log in to resquest access to the document




V Gauttier, V Pichard, D. Aubert, C Kaeppel, M Schmidt, et al.. No tumour-initiating risk associated with scAAV transduction in newborn rat liver. Gene Therapy, Nature Publishing Group, 2013, 20 (7), pp.779-784. ⟨10.1038/gt.2013.7⟩. ⟨inserm-02165748⟩



Record views