Selective killing of Leishmania amastigotes expressing a thymidine kinase suicide gene.
Selective killing of Leishmania amastigotes expressing a thymidine kinase suicide gene.
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DOI：
10.1006/expr.1996.4115
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发表时间：
1997
影响因子：
2.1
通讯作者：
Anthony Muyombwe;Martin Olivier;Marc Ouellette;Barbara Papadopoulou
中科院分区：
文献类型：
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作者：
Anthony Muyombwe;Martin Olivier;Marc Ouellette;Barbara Papadopoulou
将单纯疱疹1型病毒的胸苷激酶基因转染到几种利什曼原虫中以产生药物敏感突变体。胸苷激酶基因的表达本身对利什曼原虫细胞无害，但它能够将核苷类似物更昔洛韦磷酸化为高毒性产物。除了产生对更昔洛韦高度敏感的利什曼原虫前鞭毛体外，胸苷激酶基因在被鼠或人巨噬细胞吞噬的无鞭毛体中表达相似。表达胸苷激酶的主要利什曼原虫无鞭毛体用更昔洛韦治疗时消除了85%。在感染阶段选择性杀死表达自杀基因的寄生虫可能为控制寄生虫感染提出新的策略。
The thymidine kinase gene of Herpes simplex type-1 virus was transfected into several Leishmania species to create drug-sensitive mutants. Expression of the thymidine kinase gene is not by itself harmful to Leishmania cells but it is capable of phosphorylating ganciclovir, a nucleoside analog, into a highly toxic product. In addition to the generation of Leishmania promastigotes highly sensitive to ganciclovir, the thymidine kinase gene was expressed similarly by amastigotes engulfed either by murine or by human macrophages. Leishmania major amastigotes expressing thymidine kinase were eliminated by 85% when treated with ganciclovir. Selective killing of parasites expressing suicide genes at their infective stage could suggest novel strategies for controlling parasitic infections.