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介导的基因组编辑技术及其诱导多能干细胞的产生能力 病人血液样本中的细胞(IPSCs)将医学置于我们能力革命的边缘 来治疗，甚至治愈一系列基于基因组的疾病。UT的总体目标 西南韦尔斯通肌营养不良专科研究中心是为提高治疗水平提供的 Duchenne肌营养不良症(DMD)患者通过开发一种名为“肌肉编辑”的新治疗策略。 该中心围绕五个组成部分而建。其中包括：两个相互关联的研究项目 (1)致力于优化CRISPR/Cas9介导的DMD外显子跳过应用的工具 永久性地恢复营养不良蛋白的功能，以及其他(2)将确定遗传和生物标记物关联的 营养不良症患者的心脏表型[即DMD和Becker肌营养不良症(BMD)] 是人类IPSCs的主要来源。这些项目将得到三个项目的补充和支持 核心(A)管理核心，还将指导患者外展和教育，(B)Myoediting Science 研究资源核心，它将从DMD/BMD患者中生成DMD/BMD IPSCs并将其区分开来 转化为IPSC来源的心肌细胞以及容纳DMD/BMD生物库，该生物库将存储相关的临床 数据以及每个基因突变的有效指南RNA，以及(C)训练核心，这将增强 教育环境，以招募、培训和保持下一代变革性调查人员 专注于解决肌营养不良症的挑战。我们坚信MyoEditing将提供一种 用于治疗数千名DMD患者的创新治疗模式，并提供了期待已久的 希望这些被DMD摧毁的患者和他们的家人。