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The equine herpes virus 4 thymidine kinase is a better suicide gene than the human herpes virus 1 thymidine kinase

Gene Therapy volume 6, pages 1638–1642 (1999)Cite this article

Abstract

The herpes simplex virus type 1 thymidine kinase suicide gene (HSV1tk) together with ganciclovir (GCV) have been successfully used for in vivo treatment of various experimental tumors, and many clinical trials using this system have been launched. With the aim to improve this therapeutic system, we compared the potential efficacy of different herpes virus derived thymidine kinases (HSV1, varicella-zoster virus, equine herpes virus type-4 and Epstein–Barr virus) as suicide genes in association with the nucleoside analogs acyclovir, ganciclovir and bromovinyldeoxyur- idine. Using various murine and human cell lines expressing these viral tk, we show that HSV1- and EHV4tk are the more efficient suicide genes for the different nucleoside analogs tested. Moreover, EHV4tk expressing murine and human cells were three- to 12-fold more sensitive to GCV than HSV1tk expressing cells. This was correlated with the presence of five-fold higher amounts of the toxic triphosphated-GCV in EHV4- versus HSV1tk expressing cells. Altogether, these experiments underline the potential advantages of the EHV4tk as a suicide gene.

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Acknowledgements

This work was supported in part by the Agence Nationale de Recherche sur le SIDA, the Université Pierre et Marie Curie, the Centre National de la Recherche Scientifique and the Assistance Publique – Hôpitaux de Paris. Laurence Loubière was a fellow of the Association pour la Recherche sur le Cancer.

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Authors and Affiliations

  1. Laboratoire de Biologie et Thérapeutique des Pathologies Immunitaires, UPMC, CNRS ESA 7087, CERVI, Hôpital de la Pitié, 83, Boulevard de l’Hôpital, Paris, 75651, Cedex 13, France

    L Loubière, M Tiraby, E Brisson, J C Zhao-Emonet & D Klatzmann

  2. Laboratoire CAYLA, ZI Montaudran, Toulouse, France

    M Tiraby & G Tiraby

  3. Institut de Pharmacologie et de Biologie Structurale, CNRS UPR A9062, Toulouse, France

    C Cazaux

  4. Génopoïétic, Paris, France

    M Grisoni

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  1. L Loubière
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  2. M Tiraby
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  4. E Brisson
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  6. J C Zhao-Emonet
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Loubière, L., Tiraby, M., Cazaux, C. et al. The equine herpes virus 4 thymidine kinase is a better suicide gene than the human herpes virus 1 thymidine kinase. Gene Ther 6, 1638–1642 (1999). https://doi.org/10.1038/sj.gt.3300993

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  • DOI: https://doi.org/10.1038/sj.gt.3300993

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