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

使用辐射诱导启动子研究胶质母细胞瘤安全有效的基因治疗。

• 批准号: 13671443
• 负责人: TOKUNAGA Yoshiharu
• 金额: $ 2.24万
• 依托单位: Nagasaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671443/
• 关键词: gliobastoma; radiation; suicide gene therapy; cre-loxP; HSV-TK; radiation inducible; 遺伝子治療; Cre; loxP; 放射線治療; Egr-1; 自殺遺伝子; HVJ-liposome

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.

组织或肿瘤特异性启动子为癌症基因治疗的选择性靶向提供了一种有前途的方法，因为此类启动子能够以细胞类型特异性方式表达靶基因。然而，细胞类型特异性启动子的活性普遍较低，限制了其作为肿瘤分子靶向的临床应用。因此，为了建立放射诱导的肿瘤细胞特异性基因治疗胶质母细胞瘤，我们开发了基于cre-loxP的载体系统。cre载体携带Egr-1启动子和cre基因，cre基因转录体与另一个载体的loxP位点拼接，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使用两个相同的载体系统的cre-loxP系统的复杂性造成的。因此，我们现在正在研究更有效的基因治疗系统，使用由辐射诱导型Egr-1启动子驱动的简单载体系统。