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Hepatoma cell-specific ganciclovir-mediated toxicity of a lentivirally transduced HSV-TkEGFP fusion protein gene placed under the control of rat alpha-fetoprotein gene regulatory sequences

Cancer Gene Therapy volume 10, pages 689–695 (2003)Cite this article

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.

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Authors and Affiliations

  1. Département de thérapie cellulaire et génique, Etablissement Français du Sang Alpes-Méditerranée, Marseille, France

    Rathviro Uch, René Gérolami, Patrice Mannoni & Claude Bagnis

  2. INSERM U559, Faculté de Médecine de la Timone, Marseille, France

    Rathviro Uch, René Gérolami & Sylvie Mathieu

  3. INSERM U 370, Faculté Necker, Paris, France

    Jamila Faivre

  4. Service de transplantation hépatique, Hôpital de La Conception, Marseille, France

    Jean Hardwigsen

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  1. Rathviro Uch
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  2. René Gérolami
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  3. Jamila Faivre
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  4. Jean Hardwigsen
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  5. Sylvie Mathieu
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  7. Claude Bagnis
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Correspondence to Claude Bagnis.

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Uch, R., Gérolami, R., Faivre, J. et al. Hepatoma cell-specific ganciclovir-mediated toxicity of a lentivirally transduced HSV-TkEGFP fusion protein gene placed under the control of rat alpha-fetoprotein gene regulatory sequences. Cancer Gene Ther 10, 689–695 (2003). https://doi.org/10.1038/sj.cgt.7700621

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  • DOI: https://doi.org/10.1038/sj.cgt.7700621

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