Genome Editing Core

核心5 -基因组编辑核心：摘要 研究糖尿病及其并发症的潜在机制需要相关的实验模型。 近年来，诱导多能干细胞（iPS）为研究疾病相关性提供了独特的手段。 患者特异性细胞中的分子途径。基因组编辑工具的发展，如CRISPR- Cas9系统使精确工程细胞成为可能，并使用iPS进一步完善疾病建模 细胞iPS衍生细胞的研究对于人类细胞缺陷的建模是非常宝贵的。但是，细胞- 基础实验不能充分反映与糖尿病相关的全身变化。动物模型是 同样重要和必要的是补充体外实验。基因组编辑技术 也使得快速有效地产生新的糖尿病相关小鼠模型成为可能， 探究疾病机制。 基因组编辑核心（GEC）将为研究人员创造新颖独特的人类基因组提供一个平台。 细胞模型和小鼠模型来研究糖尿病及其并发症。GEC将使用最先进的 本发明提供了一种方法，以1）产生患者特异性iPS细胞系，2）编辑iPS和iPS衍生细胞的基因组， 探测单个基因或基因变体，和3）通过基因敲低，敲入， 淘汰或替换。除了提供这些服务外，GEC还将提供咨询、试剂和工具 用于实验模型的基因组编辑，并为iPS细胞的生成和操作提供培训 线与新提议的临床转化研究核心合作，GEC还将为 作为来自1型糖尿病、2型糖尿病和2型糖尿病的大量独特iPS细胞系的储存库， MODY患者来源于Joslin的广泛患者人群。总而言之，GEC将构成一个 通过促进相关模型的定制生成，为糖尿病研究的各个方面提供宝贵的资源 系统.

CORE 5 - GENOME EDITING CORE: ABSTRACT Investigating mechanisms that underlie diabetes and its complications requires relevant experimental models. In recent years, induced pluripotent stem (iPS) cells have provided a unique means to study disease-relevant molecular pathways in patient-specific cells. The development of genome editing tools such as the CRISPR- Cas9 system has made it possible to accurately engineer cells and further refine disease modeling using iPS cells. Studies of iPS-derived cells are invaluable to the modeling of human cellular defects. However, cell- based experiments do not adequately reflect systemic changes associated with diabetes. Animal models are equally important and necessary to complement in vitro experimentation. Genome editing techniques have also made it possible to very quickly and efficiently generate new diabetes-relevant mouse models to interrogate mechanisms of disease. The Genome Editing Core (GEC) will provide a platform for investigators to create novel and unique human cellular models and mouse models to study diabetes and its complications. The GEC will use state-of-the-art methodology to 1) generate patient-specific iPS cell lines, 2) edit the genome of iPS and iPS-derived cells to probe individual genes or gene variants and 3) generate custom mouse models by gene knockdown, knock-in, knock-out or replacement. In addition to providing these services, the GEC will offer advice, reagents and tools for genome editing of experimental models and offer training for the generation and manipulation of iPS cell lines. In collaboration with the newly proposed Clinical Translational Research Core, the GEC will also serve as a repository for a large collection of unique iPS cell lines derived from type 1 diabetes, type 2 diabetes and MODY patients sourced from Joslin's extensive patient population. In sum, the GEC will constitute an invaluable resource for all aspects of diabetes research by facilitating the custom generation of relevant model systems.