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

被引:0
作者
L Loubière
M Tiraby
C Cazaux
E Brisson
M Grisoni
J C Zhao-Emonet
G Tiraby
D Klatzmann
机构
[1] Laboratoire de Biologie et Thérapeutique des Pathologies Immunitaires,
[2] UPMC,undefined
[3] CNRS ESA 7087,undefined
[4] CERVI,undefined
[5] Hôpital de la Pitié,undefined
[6] Laboratoire CAYLA,undefined
[7] ZI Montaudran,undefined
[8] Institut de Pharmacologie et de Biologie Structurale,undefined
[9] CNRS UPR A9062,undefined
[10] Génopoïétic,undefined
来源
Gene Therapy | 1999年 / 6卷
关键词
nucleoside analogs; cancer; fusion proteins;
D O I
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中图分类号
学科分类号
摘要
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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页码:1638 / 1642
页数:4
相关论文
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