Investigation for safe and efficient gene therapy for glioblastomas using radiation inducible promoters.

组织或肿瘤特异性启动子为肿瘤基因治疗的选择性靶向提供了一种很有前途的方法，因为这些启动子能够以细胞类型特异性的方式表达靶基因。然而，细胞型特异性启动子的活性普遍较低，限制了分子肿瘤靶向的临床应用。因此，为了建立针对胶质母细胞瘤的辐射诱导的肿瘤细胞特异性基因治疗，我们开发了基于cre-loxP的载体系统。Cre载体含有Egr-1启动子和cre基因，转录产物与携带loxP基因的另一载体的loxP位点相连，该载体表达由CMV启动子驱动的单纯疱疹病毒胸苷激酶(HSV-TK)基因。我们认为这些结果是由于这个cre-loxP系统的复杂性，使用了两个相同的载体系统。因此，我们现在正在研究更有效的基因治疗系统，使用辐射诱导的Egr-1启动子驱动的简单载体系统。

Tissue- or tumor-specific promoters offer a promising approach to the selective targeting of cancer gene therapy because such promoters are able to express a target gene in a cell-type specific manner. However, the activity of cell-type specific promoter is generally low, being the limitation of clinical usefulness for molecular tumor targeting. To, therefore, establish radiation inducible tumor cell-specific gene therapy for glioblastomas, we developed cre-loxP based vector system. The cre vector harbors Egr-1 promoter and cre gene, which transcriptant splices the loxP site of the other vector, which harbors the loxP gene, and this vector expresses herpes simplex virus thymidine kinase (HSV-TK) gene driven by CMV promoter.To date, we could reach significant results neither in vitro gene therapy nor in vivo experiment. We think these results were due to complexity of this cre-loxP system, using two identical vector systems.So, we are now investigating more effective gene therapy system, using simple vector system driven by the radiation inducible Egr-1 promoter.