A triple suicide gene strategy that improves therapeutic effects and incorporates multimodality molecular imaging for monitoring gene functions
A triple suicide gene strategy that improves therapeutic effects and incorporates multimodality molecular imaging for monitoring gene functions
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DOI：
10.1038/cgt.2013.28
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发表时间：
2013-06-01
影响因子：
6.4
通讯作者：
Li, G. C.
中科院分区：
文献类型：
--
作者：
Xing, L.;Sun, X.;Li, G. C.
基因导向酶药物前治疗（GDEPT），或称自杀基因治疗，已在临床试验中显示出前景。在这项使用稳定细胞系和异种移植肿瘤模型的临床前研究中，我们表明三重自杀基因GDEPT方法比以前的方法产生更高的治疗效果。重要的是，所有三个基因（胸苷激酶，胞嘧啶脱氨酶和尿嘧啶磷酸核糖基转移酶）同时作为GDEPT的效应器和多模态分子成像（MMI）的标记，使用正电子发射断层扫描，磁共振波谱和光学（荧光和生物发光）技术。结果表明，MMI可以评估三重自杀基因的分布和功能/活性。这些基因的同时表达显著增强了体外和体内的前药细胞毒性和放射敏感性。
Gene-directed enzyme prodrug therapy (GDEPT), or suicide gene therapy, has shown promise in clinical trials. In this preclinical study using stable cell lines and xenograft tumor models, we show that a triple-suicide-gene GDEPT approach produce enhanced therapeutic efficacy over previous methods. Importantly, all the three genes (thymidine kinase, cytosine deaminase and uracil phosphoribosyltransferase) function simultaneously as effectors for GDEPT and markers for multimodality molecular imaging (MMI), using positron emission tomography, magnetic resonance spectroscopy and optical (fluorescent and bioluminescent) techniques. It was demonstrated that MMI can evaluate the distribution and function/activity of the triple suicide gene. The concomitant expression of these genes significantly enhances prodrug cytotoxicity and radiosensitivity in vitro and in vivo.