Myoediting of Duchenne Muscular Dystrophy

总体组件的项目总结/摘要 CRISPR/Cas9介导的基因组编辑技术和产生诱导多能干细胞的能力 从病人血液样本中提取的多能干细胞（iPSC）使医学处于一场革命的边缘， 来治疗，甚至治愈，一系列基因疾病。UT的总体目标 西南威尔斯通肌营养不良专科研究中心是为提高治疗提供 通过开发一种名为“myoediting”的新治疗策略，对杜氏肌营养不良症（DMD）患者进行治疗。 该中心是围绕五个组成部分建立的。其中包括：两个相互关联的研究项目 (1)一个将致力于优化应用CRISPR/Cas9介导的DMD外显子跳跃的工具， 永久恢复肌营养不良蛋白功能，另一个（2）将确定遗传和生物标志物关联 肌营养不良症患者的心脏表型[即DMD和Becker肌营养不良症（BMD）] 并作为人类iPSC的主要来源。这些项目将得到以下三个方面的补充和支持： 核心（A）管理核心，也将指导患者外展和教育，（B）Myoediting科学 研究资源核心，将从DMD/BMD患者中产生DMD/BMD iPSCs，并将其分化为 植入iPSC衍生的心肌细胞，并容纳DMD/BMD生物库，该生物库将存储相关的临床 数据以及每种基因突变的经验证的指导RNA，以及（C）训练核心，其将增强 教育环境，以招募，培训和维护下一代变革调查员 专注于应对肌肉萎缩症的挑战。我们坚信myoediting将提供一个 创新的治疗模式，用于治疗成千上万的DMD患者，并提供期待已久的 希望这些患者和他们的家庭受到DMD的打击。

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.