Gene Editing Core

项目摘要基因编辑核心 麻省理工学院和哈佛布罗德研究所的Liu实验室将作为该计划的基因编辑核心。 开发定制的编辑策略，最大限度地提高治疗性编辑，同时最大限度地减少不希望的 副产品是所有研究项目成功的重要因素。一个集中的基因编辑核心，由Liu担任工作人员 实验室成员将通过防止基因编辑分析中的瓶颈来提高该计划的效率 并确保拟议项目所用方法和材料的一致性。基因编辑核心 三个中心目标：1）评估所有研究项目中来自分离细胞系的靶向编辑活性， 2）评估处理细胞中的脱靶编辑活性; 3）优化基因编辑 治疗靶点的技术。核心将在对基因进行严格分析方面发挥重要作用。 编辑我们开拓者项目IND提交的结果，与临床前小鼠密切协调， Model Core分析来自大规模疗效研究的样本。此外，核心将促进成熟 通过继续开发最新的基础编辑和/或主要编辑技术， 代表每个追随者项目治疗目标的模型系统。核心与核心之间的协同作用 Follower Projects将共同开发新的基因组编辑工具，最大限度地提高靶向编辑 效率，最小化不期望的基因编辑副产物和脱靶编辑事件，并最大化 与潜在治疗相关性的体内递送方法的相容性。

PROJECT SUMMARY GENE EDITING CORE The Liu laboratory at the Broad Institute of MIT and Harvard will serve as the Gene Editing Core for the Program. Developing customized editing strategies that maximize therapeutic editing while minimizing undesired byproducts is important for the success of all Research Projects. A centralized Gene Editing Core staffed by Liu laboratory members will enhance the Program's efficiency by preventing bottlenecks in gene editing analyses and ensuring consistency in methods and materials used in the proposed projects. The Gene Editing Core has three central aims: 1) to assess on-target editing activity across all Research Projects from isolated cell lines and from animal tissue samples; 2) to assess off-target editing activity in treated cells; 3) to optimize gene editing technologies for therapeutic targets. The Core will play an essential role in generating rigorous analyses of gene editing outcomes for the IND submission of our trailblazer project, coordinating closely with the Preclinical Mouse Model Core analyze samples from large-scale efficacy studies. Additionally, the Core will facilitate the maturation of the Follower Projects by continuing to develop the latest base editing and/or prime editing technologies in model systems representative of each Follower Project's therapeutic target. Synergy between the Core and the Follower Projects will enable the co-development of new genome editing tools that maximize on-target editing efficiencies, minimize undesirable gene editing byproducts and off-target editing events, and maximize compatibility with in vivo delivery methods of potential therapeutic relevance.