Myoediting of Duchenne Muscular Dystrophy

杜氏肌营养不良症的肌编辑

• 批准号: 10261402
• 负责人: RHONDA BASSEL-DUBY
• 金额: $ 160.58万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-15 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10261402
• 关键词: Address; Animal Model; Awareness; Basic Science; Becker Muscular Dystrophy; Biology; Biotechnology; Blood; Boston; CRISPR/Cas technology; Cardiac; Cardiac Myocytes; Cardiomyopathies; Caregivers; Cell Line; Child; Clinic; Clinical; Clinical Data; Clinical Research; Clinical Services; Coin; Communities; Community Outreach; Complement; DNA Sequence Alteration; Dedications; Development; Discipline; Disease; Duchenne muscular dystrophy; Dystrophin; Education; Education and Outreach; Ensure; Family; Foundations; Generations; Genetic Markers; Genome; Goals; Guide RNA; Human; Institution; Knowledge; Mediating; Medical center; Medicine; Mission; Modality; Modeling; Muscle; Muscular Dystrophies; Neuromuscular Diseases; Patients; Phenotype; Publications; Research; Research Personnel; Research Project Grants; Resources; Sampling; Schools; Science; Scientist; Series; Source; System; Technology; Therapeutic; Training; Translating; Translational Research; University Hospitals; Vision; Work; base; bench to bedside; biobank; biomedical scientist; clinical care; clinically relevant; collaborative environment; design; dystrophinopathy; education resources; educational atmosphere; exon skipping; genome editing; improved; induced pluripotent stem cell; innovation; insight; lectures; member; neuromuscular; new technology; next generation; novel therapeutic intervention; novel therapeutics; patient advocacy group; patient outreach; preclinical study; programs; recruit; regenerative; research study; standard of care; tool; translational study

Project Summary/Abstract for the Overall Component The techniques of CRISPR/Cas9-mediated genomic editing and the ability to generate induced pluripotent stem cells (iPSCs) from a sample of a patient’s blood have placed medicine on the brink of a revolution in our ability to treat, and perhaps even cure, a broad range of genome-based diseases. The overall goal of the UT Southwestern Wellstone Muscular Dystrophy Specialized Research Center is to improve the treatment provided to Duchenne muscular dystrophy (DMD) patients by developing a new therapeutic strategy called “myoediting”. The Center has been built around five integral components. These include: two inter-related research projects (1) one that will work to optimize the tools for application of CRISPR/Cas9-mediated DMD exon skipping to permanently restore dystrophin function, and the other (2) that will identify genetic and biomarker associations with cardiac phenotypes in patients with dystrophinopathies [i.e. DMD and Becker muscular dystrophy (BMD)] and serve as a primary source for human iPSCs. These projects will be complemented and supported by three Cores (A) an Administrative Core, that will also direct patient outreach and education, (B) a Myoediting Scientific Research Resource Core, which will generate DMD/BMD iPSCs from DMD/BMD patients and differentiate them into iPSC-derived cardiomyocytes as well as house the DMD/BMD Biobank, which will store relevant clinical data as well as validated guide RNAs for each genetic mutation, and (C) a Training Core, which will enhance the educational environment in order to recruit, train, and maintain the next generation of transformative investigators focused on addressing the challenges of muscular dystrophy. We firmly believe myoediting will offer an innovative therapeutic modality for the treatment of many thousands of DMD patients and offer a long awaited hope to these patients and their families devastated by DMD.

整体组件的项目摘要/摘要 CRISPR/CAS9介导的基因组编辑的技术和产生诱导多能茎的能力 患者血液样本中的细胞（IPSC）已将药物放在我们能力的革命眨眼之间 治疗甚至可以治愈各种基于基因组的疾病。 UT的总体目标 西南井石肌肉营养不良专业研究中心是改善所提供的治疗 通过制定一种称为“ Myoediting”的新治疗策略，以Duchenne肌肉营养不良（DMD）患者。 该中心已建成五个整体组件。其中包括：两个相互关联的研究项目 （1）将有助于优化应用CRISPR/CAS9介导的DMD外显子的工具 永久恢复肌营养不良蛋白的功能，另一个（2）将识别遗传和生物标志物关联 患有肌营养不良患者的心脏表型[即DMD和Becker肌肉营养不良（BMD）] 并作为人IPSC的主要来源。这些项目将由三个项目完成和支持 核心（a）行政核心，还将指导患者的外展和教育，（b）肌组织科学 研究资源核心将生成来自DMD/BMD患者的DMD/BMD IPSC并区分它们 进入IPSC衍生的心肌细胞以及HOUSE DMD/BMD生物库，它将存储相关的临床 数据以及验证的每个遗传突变的指南RNA，以及（c）训练核心，这将增强 教育环境以招募，培训和维护下一代变革性研究人员 专注于应对肌肉营养不良的挑战。我们首先相信Myoediting会提供 用于治疗数千名DMD患者的创新治疗方式，并提供了期待已久的 希望这些患者及其家人被DMD毁灭。