Gene Editing Core

基因编辑核心

基本信息

批准号：
10668765
负责人：
DAVID R LIU
金额：
$ 40.85万
依托单位：
JACKSON LABORATORY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-05-16 至 2028-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10668765
关键词：
Animals Archives Biological Biological Assay Biological Models Cell Line Cell Separation Cells Clinic Complex Custom DNA DNA Double Strand Break Data Deaminase Ensure Enzymes Equipment Event Future Genes Genome Genomic DNA Genomics Goals High-Throughput Nucleotide Sequencing In Vitro Individual Laboratories Libraries Mammalian Cell Methods Monitor Outcome Play Process Program Efficiency Recording of previous events Reporting Research Project Grants Ribonucleoproteins Role Running Sampling Site Technology Therapeutic Tissue Sample Tissues Validation Viral Vector analysis pipeline animal tissue base editing candidate identification cell type data analysis pipeline design detection method efficacy study genome editing genome-wide human DNA in vivo member mouse model nervous system disorder off-target site pre-clinical prevent prime editing programs success synergism therapeutic candidate therapeutic genome editing therapeutic target tool vector

项目摘要

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.

项目概要基因编辑核心麻省理工学院和哈佛大学博德研究所的刘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需要的编辑副产品对于所有研究项目的成功都很重要。由刘领导的集中式基因编辑核心实验室成员将通过防止基因编辑分析的瓶颈来提高该计划的效率确保拟议项目中使用的方法和材料的一致性。基因编辑核心有三个中心目标：1）评估所有研究项目中分离细胞系的靶向编辑活性，来自动物组织样本； 2) 评估处理细胞中的脱靶编辑活性； 3）优化基因编辑治疗目标的技术。核心将在进行严格的基因分析方面发挥重要作用与临床前小鼠密切协调，编辑我们开拓者项目 IND 提交的结果核心模型分析来自大规模功效研究的样本。此外，核心将促进成熟通过继续开发最新的碱基编辑和/或主要编辑技术来实现追随者项目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追随者项目将共同开发新的基因组编辑工具，以最大限度地实现目标编辑效率，最大限度地减少不需要的基因编辑副产品和脱靶编辑事件，并最大限度地提高与潜在治疗相关的体内递送方法的兼容性。