Hepatoma cell-specific ganciclovir-mediated toxicity of a lentivirally transduced HSV-TkEGFP fusion protein gene placed under the control of rat alpha-fetoprotein gene ... View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2003-09

AUTHORS

Claude Bagnis, Jamila Faivre, Jean Hardwigsen, Patrice Mannoni, Rathviro Uch, René Gérolami, Sylvie Mathieu

ABSTRACT

Suicide gene therapy combining herpes simplex virus thymidine kinase gene transfer and ganciclovir administration can be envisioned as a powerful therapeutical approach in the treatment of hepatocellular carcinoma; however, safety issues regarding transgene expression in parenchyma cells have to be addressed. In this study, we constructed LATKW, a lentiviral vector expressing the HSV-TkEGFP gene placed under the control of the promoter elements that control the expression of the rat alpha-fetoprotein, and assayed its specific expression in vitro in hepatocarcinoma and nonhepatocarcinoma human cell lines, and in epidermal growth factor stimulated human primary hepatocytes. Using LATKW, a strong expression of the transgene was found in transduced hepatocarcinoma cells compared to a very low expression in nonhepatocarcinoma human cell lines, as assessed by Northern blot, RT-PCR, FACS analysis and ganciclovir-mediated toxicity assay, and no expression was found in lentivirally transduced normal human hepatocytes. Altogether, these results demonstrate the possibility to use a lentivirally transduced expression unit containing the rat alpha-fetoprotein promoter to restrict the HSV-TK-mediated induced GCV sensitivity to human hepatocarcinoma cells. More... »

PAGES

689

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.cgt.7700621

DOI

http://dx.doi.org/10.1038/sj.cgt.7700621

DIMENSIONS

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PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/12944988


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