Construction of a stimulation-responsive gene regulation system and its application for gene therapy

我们已经建立了一个逆转录病毒载体系统，以稳定地导入由构建的辐射响应启动子和目的基因组成的基因盒。在一个表达荧光素酶基因的细胞系中，我们证明了荧光素酶基因在辐射中的表达是可能的。此外，利用已建立的表达自杀基因FCY：：Fur基因的细胞系，可以在辐射照射时增强细胞杀伤效果，显示出辐射依赖的自杀基因治疗的体外模拟。此外，使用另一组顺式元件，我们成功地获得了在前列腺癌细胞系中有效工作的辐射反应启动子。此外，我们发现超声波改变了可能参与细胞对超声波反应的microRNAs的表达。此外，我们还表明，通过超声作用降低其表达的microRNAs的靶序列与超声反应启动子结合时，可能是一个更微调的超声介导的基因调控系统。

We have established a retrovirus vector system to stably introduce a gene cassette consisting of a constructed radiation responsive promoter and a gene of interest. In a cell line expressing the luciferase gene, we showed expression of the luciferase gene was possible with radiation. In addition, with an established cell line expressing the fcy :: fur gene, a suicide gene, it was possible to enhance cell killing effect when radiation was delivered, showing radiation dependent suicide gene therapy simulation in vitro. Furthermore, using another set of cis-elements, we successfully obtained radiation responsive promoters effectively working in a prostate cancer cell line. Moreover, we found that sonication changed expressions of microRNAs that could be involved in response of a cell to ultrasound. In addition, we showed that target sequences of microRNAs that decrease their expressions by sonication could be a more fine-tuned ultrasound mediated gene regulation system when combined with an ultrasound responsive promoter.