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【编译】一个新的自杀基因
Development of an inducible suicide gene system based on human caspase 8
来源
Cancer Gene Therapy advance online publication 4 March 2005;
doi:10.1038/sj.cgt.7700825
摘要原文
Suicide gene-therapy strategies are promising approaches in treating various diseases such as cancers, atherosclerosis, and graft-versus-host-disease. Here, we describe the development of a new effector gene based on inducing functional caspase 8, the initiator caspase in the death-receptor pathway. We constructed vectors encoding a constitutively active form of human caspase 8 (CC8), and demonstrated the efficient killing of a variety of cell types in transfection and lentivirus-transduction assays. We then analyzed the ability to control the apoptotic activity of a caspase 8-derived construct through the ARIADÔ homodimerization system (FKC8), a system shown to be extremely effective in several cellular models upon retroviral and lentiviral gene transfer. Similarly, two transcription-regulation systems, muristerone-regulated and Tet-On, were tested to control the expression of CC8. The homodimerization-regulated system FKC8 was shown to be the most efficient system with low background activity in noninduced conditions. In the presence of a dimerizer, it was as active as the activated Tet-On system. From our data, we conclude that the dimerizer-dependent human caspase 8 represents a highly inducible and very powerful system to eradicate transduced cell populations. In addition to its application in experimental gene therapy, this variant may be highly useful for mechanistic research related to apoptosis.
原文链接
http://www.nature.com/cgi-taf/dynapage.taf?file=/cgt/journal/vaop/ncurrent/abs/7700825a.html
编译
自杀基因疗法治疗各种疾病（如癌，动脉硬化和移植物抗宿主病）是很有前途的。这里，描述了一个基于诱导功能性凋亡蛋白酶8的新受动基因的研究。科学家构建了人凋亡蛋白酶8的编码组成活性载体（CC8），并且证明其在转染和慢病毒转导分析中可以有效杀死各种细胞。然后，研究者分析了通过ARIADÔ同种类接收器系统（FKC8）——一个被证明作用在逆转录和慢病毒属基因转移的极为有效的细胞模型系统——控制凋亡蛋白酶8起源的模型的凋亡活性能力。相似地，两个转录控制系统（幕黎甾酮调节和Tet-on）用来控制CC8表达。同种类接受调节体系FKC8被证明是在非诱导情况下只需很低的活性的最有效系统。呈现接受的情况下，它可以象活化的Tet-on系统一样活跃。我们总结出接受依赖的人凋亡蛋白酶8是一个高度可诱导的，并且除去转导细胞种群的有力体系。另外，它应用在实验基因治疗中，这种变异体可能对凋亡相关的机制研究极为有用。
注：Saitoh等选择了一个用四环素(tetracycline,Tet)衍生物来控制转基因产物表达量的方法，即将注射强力霉素后诱导的一个启动子结合到POMC基因上，此称之为Tet-on基因表达系统。 qq6108 站友辛苦，感谢一如既往的对于国外期刊的编译工作！ 也感谢丁香园给我提供了锻炼自己的专业英语翻译的机会，同时学习专业知识，并和大家共同学习。 [标签:content1][标签:content2]
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作者:admin@医学,生命科学 2011-04-23 05:14
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