权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Optogenetic control over transgene expression for the therapy of brain and spine

光遗传学控制转基因表达用于治疗大脑和脊柱

基本信息

批准号：
9255405
负责人：
Max Myakishev-Rempel
金额：
$ 22.01万
依托单位：
LOCALIZED THERAPEUTICS, LLC
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-08-01 至 2019-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9255405
关键词：
AP 1903 reagent Adverse effects Alpha Cell Alzheimer&apos s Disease Anti-Inflammatory Agents Anti-inflammatory Antibodies Automobile Driving Benchmarking Biological Bipolar Disorder Blood - brain barrier anatomy Bone Marrow Stem Cell Brain Brain Injuries CASP9 gene Cell Culture Techniques Cell Cycle Kinetics Cell Therapy Cell Transplants Cells Central Nervous System Diseases Cerebrospinal Fluid Cerebrum Characteristics Chronic Crohn&apos s disease Disease Disease model Drug Delivery Systems Epilepsy Etanercept Evaluation Flow Cytometry Gene-Modified Genetic Transcription Helmet Human Humira Immunity Infection Injectable Injury Intrathecal Injections Kinetics Light Major Depressive Disorder Measures Mediating Mental disorders Messenger RNA Methods Microscopy Multiple Sclerosis Mus Neuraxis Parkinson Disease Patients Performance Peripheral Pharmaceutical Preparations Phase Procedures Production Proteins Psoriasis Quality of life Regulation Reporter Rheumatoid Arthritis Risk Safety Self Administration Spinal Cord Diseases Stem cells Stroke Suicide Surface System TNF gene Technology Testing Transcriptional Regulation Transgenes Transplantation Vertebral column accomplished suicide dosage genetically modified cells hybrid antibody improved in vivo in vivo imaging innovation irradiation mouse model neuroinflammation neuropsychiatric disorder neuropsychiatry novel novel strategies optogenetics response small molecule suicide gene synthetic biology therapeutic protein tool transgene expression

项目摘要

Optogenetic control over transgene expression for the therapy of brain and spine Abstract Gene modified stem cells are a powerful tool for the production of secretable therapeutic proteins in the body. Yet, there is a valid concern over their safety since there is no way to control them once they have been transplanted. We propose to utilize optogenetic control of transcription (ORT) to externally control secretion of the therapeutic protein using red light. ORT would improve the efficacy and safety of the therapy by repeated remote activation of transgene synthesis with red light delivered noninvasively. For a specific disease application, we propose to use intrathecally delivered ORTdriven stem cells to produce antiinflammatory antiTNF hybrid antibodies in the subarachnoid cavity for the therapy of neuroinflammation in the brain. The ORT option would allow us to externally induce production of the antiinflammatory antibody using red light as needed. At this initial phase of the project, we propose the conceptual evaluation of the ORT system genetically embedded into bone marrow stem cells. This testing is proposed in cell culture (Aim 1) and the mouse cerebral subarachnoid cavity (Aim 2). The proposed method aims to improve the safety and efficiency of the therapy of chronic CNS disorders with episodic neuroinflammatory components by providing the benefit of remote control of the timing and dosage of the therapy.

光遗传学控制转基因表达用于脑和脊柱治疗抽象的基因修饰干细胞是在体内产生可分泌的治疗性蛋白质的强大工具。然而，人们对它们的安全存在合理的担忧，因为一旦它们被移植就无法控制它们。我们建议利用转录的光遗传学控制 (ORT) 从外部控制治疗性蛋白质的分泌使用红光。 ORT 将通过重复远程激活转基因来提高治疗的功效和安全性使用红光进行非侵入性合成。对于特定疾病的应用，我们建议鞘内使用递送 ORT 驱动的干细胞，在蛛网膜下腔中产生抗炎抗 TNF 混合抗体用于治疗大脑神经炎症。 ORT 选项将使我们能够从外部诱导生产根据需要使用红光来检测抗炎抗体。在该项目的初始阶段，我们建议对基因嵌入骨髓干细胞的 ORT 系统进行概念评估。建议进行此测试在细胞培养（目标 1）和小鼠大脑蛛网膜下腔（目标 2）中。所提出的方法旨在改善具有偶发性神经炎症成分的慢性中枢神经系统疾病治疗的安全性和有效性提供远程控制治疗时间和剂量的好处。