Infrared-activated promoter for gene therapy of arthritis.

 描述(申请人提供)：用于关节炎基因治疗的红外激活启动子。不幸的是，目前有更多的患者死于 药物而不是疾病。虽然基因治疗是一种很有前途的小分子药物的替代方案，允许在体内产生生物制品并降低治疗成本，但由于缺乏控制转基因活动的手段，其进展一直停滞不前。由于转基因在体内长期活跃，目前的基因治疗缺乏安全性。对转基因活动的有效控制将提供安全和提高疗效。我们已经确定了一个被红外光间接激活的启动子序列，并建议将其用于基因治疗中的转基因控制。在这里，我们建议(1)通过优化启动子序列和辐射参数来优化细胞培养中近红外启动子的激活；(2)在小鼠身上测试优化的近红外启动子。该项目将为近红外光诱导基因治疗的可行性提供原理证明。除了这种控制手段，还可以通过在大部分时间保持转基因休眠，并在需要时用非燃烧红外辐射激活转基因，从而使基因治疗变得更安全，从而有效地用重复的光治疗取代小分子药物。这将允许 减少关节炎治疗中的毒副作用以及局部治疗仅选择 关节从而使身体免受全身的不良副作用。

 DESCRIPTION (provided by applicant): Infrared-activated promoter for gene therapy of arthritis. It is fair to generalize that unfortunately more patients currently die from toxicity of medications than from disease. Although gene therapy is a promising alternative to small molecule drugs allowing to produce biologics inside the body and to reduce costs of treatment, its progress has been stalled due to the lack of a means of control over the transgene activity. Since transgenes are active in the body for a long time, current gene therapy lacks safety. Effective control over transgene activity would offer safety and improve efficacy. We have identified a promoter sequence which is indirectly activated by infrared light and propose to use it to control transgenes in gene therapy. Here, we propose to (1) optimize near infrared promoter activation in cell culture by optimizing the promoter sequence and irradiation parameters; and (2) test the optimized near infrared promoter in mice. This project will serve as a proof of principle for the feasibility of near infrared light- inducible gene therapy. Addition o this means of control will allow making gene therapy safer by keeping transgenes dormant most of the time and activating them with non-burning infrared irradiation when needed thus effectively replacing small molecule medications with repeated light treatments. This will allow to reduce toxicity and side effects in arthritis therapy as well as to localize therapy only to select joints thus sparing the body from the systemic adverse side effects.