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

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.