Myoediting of Duchenne Muscular Dystrophy

杜氏肌营养不良症的肌编辑

• 批准号: 10684149
• 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/10684149
• 关键词: Address; Animal Model; Awareness; Basic Science; Becker Muscular Dystrophy; Biological Markers; Biology; Biotechnology; Blood; Boston; CRISPR/Cas technology; Cardiac; Cardiomyopathies; Caregivers; Cell Line; Child; Clinic; Clinical; Clinical Data; Clinical Research; Clinical Services; Coin; Collaborations; Communication; Communities; Community Outreach; Complement; DNA Sequence Alteration; Dedications; Development; Discipline; Disease; Duchenne muscular dystrophy; Dystrophin; Education; Ensure; Family; Foundations; Generations; Genetic; Genome; Goals; Guide RNA; Human; Institution; Knowledge; Mediating; Medical center; Medicine; Mission; Modality; Modeling; Muscle; Muscular Dystrophies; Neuromuscular Diseases; Patient Education; Patients; Phenotype; Publications; Research; Research Personnel; Research Project Grants; Resources; Sampling; Science; Scientist; Series; Source; System; Technology; Therapeutic; Training; Translating; Translational Research; University Hospitals; Vision; Work; bench to bedside; biobank; biomedical scientist; clinical care; clinical translation; clinically relevant; collaborative environment; commercialization; design; dystrophinopathy; education resources; educational atmosphere; exon skipping; genome editing; graduate school; improved; induced pluripotent stem cell; induced pluripotent stem cell derived cardiomyocytes; 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.

整个组件的项目摘要/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 来自患者血液样本的细胞（iPSC）使医学处于我们能力革命的边缘 治疗甚至治愈多种基于基因组的疾病 UT 的总体目标。 西南威尔斯通肌营养不良症专业研究中心正在改善提供的治疗 通过开发一种名为“myoediting”的新治疗策略来治疗杜氏肌营养不良症（DMD）患者。 该中心围绕五个组成部分建立，其中包括：两个相互关联的研究项目。 (1) 一种将致力于优化 CRISPR/Cas9 介导的 DMD 外显子跳跃应用工具的工具 永久恢复肌营养不良蛋白功能，另一个 (2) 将识别遗传和生物标志物关联 肌营养不良症 [即 DMD 和贝克尔肌营养不良 (BMD)] 患者的心脏表型 并作为人类 iPSC 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) 行政核心，也将指导患者外展和教育，(B) Myoediting Scientific 研究资源核心，将从 DMD/BMD 患者中生成 DMD/BMD iPSC 并区分它们 转化为 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 数据以及每个基因突变的经过验证的指导 RNA，以及 (C) 训练核心，这将增强 教育环境，以招募、培训和维持下一代变革性调查人员 我们坚信肌营养不良症将提供一个解决方案。 创新的治疗方式为成千上万的 DMD 患者提供了期待已久的治疗 希望这些被 DMD 摧毁的患者及其家人。

项目成果

The histone reader PHF7 cooperates with the SWI/SNF complex at cardiac super enhancers to promote direct reprogramming.

组蛋白阅读器 PHF7 与心脏超级增强子处的 SWI/SNF 复合物合作，促进直接重编程。

• 发表时间: 2021
• 影响因子: 21.3
• 作者: Garry, Glynnis A;Bezprozvannaya, Svetlana;Chen, Kenian;Zhou, Huanyu;Hashimoto, Hisayuki;Morales, Maria Gabriela;Liu, Ning;Bassel;Olson, Eric N
• 通讯作者: Olson, Eric N

Cardiac Myoediting Attenuates Cardiac Abnormalities in Human and Mouse Models of Duchenne Muscular Dystrophy.

心脏肌编辑可减轻杜氏肌营养不良症的人类和小鼠模型中的心脏异常。

• 发表时间: 2021-09-03
• 影响因子: 20.1
• 作者: Atmanli, Ayhan;Chai, Andreas C;Cui, Miao;Wang, Zhaoning;Nishiyama, Takahiko;Bassel;Olson, Eric N
• 通讯作者: Olson, Eric N

MOXI Is a Mitochondrial Micropeptide That Enhances Fatty Acid β-Oxidation.

MOXI 是一种线粒体微肽，可增强脂肪酸β 氧化。

• 发表时间: 2018
• 影响因子: 8.8
• 作者: Makarewich, Catherine A;Baskin, Kedryn K;Munir, Amir Z;Bezprozvannaya, Svetlana;Sharma, Gaurav;Khemtong, Chalermchai;Shah, Akansha M;McAnally, John R;Malloy, Craig R;Szweda, Luke I;Bassel;Olson, Eric N
• 通讯作者: Olson, Eric N

Trout myomaker contains 14 minisatellites and two sequence extensions but retains fusogenic function.

鳟鱼 myomaker 包含 14 个小卫星和两个序列延伸，但保留融合功能。

• 发表时间: 2019
• 作者: Landemaine, Aurélie;Ramirez;Monestier, Olivier;Sabin, Nathalie;Rescan, Pierre;Olson, Eric N;Gabillard, Jean
• 通讯作者: Gabillard, Jean

Drug treatment for spinal muscular atrophy types II and III.

II型和III型脊髓性肌萎缩症的药物治疗。

• 发表时间: 2020
• 作者: Wadman, Renske I;van der Pol, W Ludo;Bosboom, Wendy Mj;Asselman, Fay;van den Berg, Leonard H;Iannaccone, Susan T;Vrancken, Alexander Fje
• 通讯作者: Vrancken, Alexander Fje