BCM/RICE GENOME EDITING TESTING CENTER

1.摘要--总体 体细胞基因组编辑有望成为治疗人类最严重疾病的潜在方法 疾病。然而，由于临床前数据不足，许多新技术没有进展到人类身上 在动物模型中。小鼠在临床前开发管道的早期特别重要，因为它们 在发育、生理、新陈代谢和疾病方面与人类的遗传可控性和相似性。荧光 报告鼠是评估跨多个器官系统的基因组编辑效率的强大工具，并使 可以将编辑事件量化到单个单元格分辨率。藏毒致病的小鼠疾病模型 突变可用于确定可能发生的目标上和目标外编辑事件的性质、 基因组编辑方法，以及改善疾病所需的基因组编辑阈值。解决 体细胞基因组编辑的挑战是一项艰巨的跨学科工作，需要不同的专业知识 从分子生物学和生物工程到病理学和免疫学。因此，拥有资源是至关重要的 用于动物模型测试，可以将这些组件聚集在一个地方。我们将利用这些专业知识 以及我们现有的以鼠标建模为中心的NIH资助的大型项目的资源，包括我们的 目前BCM-水稻小动物检测中心(SATC)的体细胞基因组编辑(SCGE)计划， 组建BCM/水稻基因组编辑检测中心(GETC)。GETC的愿景是提供高质量的 小鼠资源和强大的体细胞基因组编辑测试管道，可以支持研究人员开发 新的基因组编辑技术，并使用这些新工具进行临床前测试。我们的目标是利用野性- 类型、基因组编辑报告和人类疾病模型小鼠品系的评价(1)疗效、组织 基因组编辑技术和传递系统的特异性和安全性以及(2)疾病基因编辑 改善特定疾病所需的方法和基因组编辑阈值。通过将鼠标集中在一起 资源和测试费-在支持和经验丰富的研究的环境中提供服务 作为一支专业团队，GETC可以确保最高的实验标准、严密性和重复性。我们期待着GETC 将产生广泛和持续的影响，支持新的基因组编辑技术和 加速将其有效和安全地部署到诊所。

1. ABSTRACT – OVERALL Somatic cell genome editing holds tremendous promise as a potential cure for the most severe of human diseases. However, many new technologies do not progress into humans because of insufficient preclinical data in animal models. Mice are particularly important early in the preclinical development pipeline because of their genetic tractability and similarities to humans in development, physiology, metabolism and disease. Fluorescent reporter mice are a powerful tool for assessing genome editing efficacy across multiple organ systems and make it possible to quantify editing events down to single cell resolution. Mouse disease models harboring pathogenic mutations can be used to determine the nature of on- and off-target editing events that may occur, the safety of a genome editing approach, and the genome editing threshold required for disease amelioration. Solving the challenges of somatic genome editing is a formidable interdisciplinary effort requiring diverse expertise ranging from molecular biology and bioengineering to pathology and immunology. Thus, it is critical to have resources for animal model testing that can bring these components together in one place. We will leverage the expertise and resources of our existing large-scale, NIH-funded projects centered around mouse modeling, including our current BCM-Rice Small Animal Testing Center (SATC) of the Somatic Cell Genome Editing (SCGE) program, to form the BCM/Rice Genome Editing Testing Center (GETC). The vision of the GETC is to offer high-quality mouse resources and robust somatic genome editing testing pipelines that can support researchers developing new genome editing technologies and conducting preclinical tests with these novel tools. Our goal is to use wild- type, genome editing reporter, and human disease model mouse lines to evaluate (1) the efficacy, tissue specificity, and safety of genome editing technologies and delivery systems and (2) disease gene editing approaches and genome editing thresholds required to ameliorate specific diseases. By centralizing mouse resources and testing fee-for-services within an environment harboring a supportive and experienced research team, the GETC can ensure the highest experimental standards, rigor, and reproducibility. We expect the GETC will make a broad and sustained impact by supporting the development of new genome editing technologies and accelerating their effective and safe deployment to the clinic.