Infrared-activated promoter for gene therapy of arthritis.

用于关节炎基因治疗的红外线激活启动子。

• 批准号: 8906120
• 负责人: Max Myakishev-Rempel
• 金额: $ 22.35万
• 依托单位: LOCALIZED THERAPEUTICS, LLC
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8906120
• 关键词: Adverse effects; Arthritis; Behavior Therapy; Biological Assay; Cell Culture Techniques; China; Chronic; DNA; Disease; Europe; FDA approved; Feedback; Gene Chips; Gene Expression; Genes; Home environment; Injection of therapeutic agent; Institution; Intra-Articular Injections; Joints; Light; Local Therapy; Luciferases; Medicine; Methods; Modeling; Mus; Organ; Pain; Patients; Performance; Pharmaceutical Preparations; Pharmacologic Substance; Phototherapy; Physical therapy; Reporter; Reporting; Research Personnel; Safety; Small Business Innovation Research Grant; Stem cells; Structure; Technology; Testing; Time; Tissues; Toxic effect; Transgenes; Treatment Cost; Ultraviolet A radiation; adeno-associated viral vector; arthritis therapy; base; cell transformation; dosage; gene therapy; gene therapy clinical trial; improved; irradiation; pill; promoter; public health relevance; research study; small molecule; success; therapeutic transgene; vector

 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.

 描述（申请人提供）：用于关节炎基因治疗的激活启动子。公平地说，不幸的是，目前有更多的患者死于 药物治疗比疾病。虽然基因治疗是一种有前途的替代小分子药物，允许在体内产生生物制剂并降低治疗成本，但由于缺乏控制转基因活性的手段，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。对转基因活性的有效控制将提供安全性并提高功效。我们已经确定了一个启动子序列，这是间接激活的红外光，并建议使用它来控制基因治疗中的转基因。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的近红外启动子激活;（2）在小鼠中测试优化的近红外启动子。本计画将作为近红外光诱导基因治疗可行性的原理证明。这种控制手段的添加将允许通过使转基因在大部分时间处于休眠状态并且在需要时用非燃烧红外辐射激活它们来使基因治疗更安全，从而有效地用重复的光治疗代替小分子药物。这将允许 减少关节炎治疗中的毒副作用， 从而使身体免受全身不良副作用。

项目成果

Optogenetic regulation of transcription.

• DOI: 10.1186/s12868-018-0411-6
• 发表时间: 2018-04-19
• 期刊: BMC neuroscience
• 影响因子: 2.4
• 作者: Polesskaya O;Baranova A;Bui S;Kondratev N;Kananykhina E;Nazarenko O;Shapiro T;Nardia FB;Kornienko V;Chandhoke V;Stadler I;Lanzafame R;Myakishev-Rempel M
• 通讯作者: Myakishev-Rempel M

On possible role of DNA electrodynamics in chromatin regulation.

• DOI: 10.1016/j.pbiomolbio.2017.12.006
• 发表时间: 2017-12
• 期刊: Progress in biophysics and molecular biology
• 影响因子: 3.8
• 作者: O. Polesskaya;Vadim V. Guschin;N. Kondratev;Irina A. Garanina;O. Nazarenko;N. Zyryanova;A. Tovmash;Abraham Mara;Tatiana Shapiro;E. Erdyneeva;Yue Zhao;Eugenia Y Kananykhina;Max Myakishev-Rempel