Genome Editing and Biological Effects Testing Section

基因组编辑及生物效应检测组

基本信息

批准号：
10773478
负责人：
William Raymond Lagor
金额：
$ 47.07万
依托单位：
BAYLOR COLLEGE OF MEDICINE
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：
2023-12-01 至 2028-11-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10773478
关键词：
Acceleration Adverse effects Alleles Animal Testing Animals Biodistribution Biological Cells Chemistry Chromosomal translocation Communities Consult Data Development Disease Disease model Enzyme-Linked Immunosorbent Assay Event Excision Fee-for-Service Plans Flow Cytometry Germ Cells Goals Health Histologic Histopathology Immune response Immunophenotyping Knockout Mice Medicine Methods Modeling Monitor Mus Mutation Organ Pathogenicity Phase Phenotype Preclinical Testing Procedures Protein Secretion Reagent Reporter Reporting Research Research Personnel Resources Rice Safety Serum Specificity System Testing Time Tissue Harvesting Tissues Toxic effect United States National Institutes of Health Universities Western Blotting Work automated image analysis base editing cell type central database college experience experimental study gene product genome editing insertion/deletion mutation interest mouse model next generation sequencing novel strategies novel therapeutic intervention novel therapeutics precision medicine prime editing programs repaired restoration somatic cell gene editing tool vector genome

Acceleration Adverse effects Alleles Animal Testing Animals Biodistribution Biological Cells Chemistry Chromosomal translocation Communities Consult Data Development Disease Disease model Enzyme-Linked Immunosorbent Assay Event Excision Fee-for-Service Plans Flow Cytometry Germ Cells Goals Health Histologic Histopathology Immune response Immunophenotyping Knockout Mice Medicine Methods Modeling Monitor Mus Mutation Organ Pathogenicity Phase Phenotype Preclinical Testing Procedures Protein Secretion Reagent Reporter Reporting Research Research Personnel Resources Rice Safety Serum Specificity System Testing Time Tissue Harvesting Tissues Toxic effect United States National Institutes of Health Universities Western Blotting Work automated image analysis base editing cell type central database college experience experimental study gene product genome editing insertion/deletion mutation interest mouse model next generation sequencing novel strategies novel therapeutic intervention novel therapeutics precision medicine prime editing programs repaired restoration somatic cell gene editing tool vector genome

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项目摘要

3. ABSTRACT – GENOME EDITING AND BIOLOGICAL EFFECTS TESTING SECTION The goal of the Genome Editing and Biological Effects Testing Section (GE-BETS) of the BCM/Rice Genome Editing Testing Section is to provide to the research community a centralized, broadly accessible, fee-for-service resource for testing genome editing delivery reagents and genome editing tools in mouse models. The GE-BETS will develop new approaches and standard operating procedures (SOPs), as well as customize analyses based on research needs. GE-BETS capitalizes on extensive local genome editing and testing experience within Baylor College of Medicine (BCM) and Rice University, originating from the BCM Knockout Mouse Phenotyping Project, Center for Precision Medicine Models, and the BCM-Rice Small Animal Testing Center of the NIH Somatic Cell Genome Editing program. In this project, GE-BETS will develop pipelines for testing of genome editing reagents in genome editing reporter and disease models and perform testing for external research partners. In Aim 1, we will perform testing of somatic genome editing systems in fluorescent reporter mice. Major deliverables include biodistribution, editing efficiency across tissues, cell type identification, and changes in health or toxicity arising from genome editing and delivery systems. In Aim 2, we will determine the efficiency, specificity, and safety of genome editing reagents in relevant disease models. We will assess on- and off-target editing by next generation sequencing in the target tissue to precisely quantify the efficiency of genome editing in the context of a pathogenic mutation. Editing efficiency will be correlated with restoration or removal of the intended gene product. These studies will inform the feasibility of new therapeutic approaches, as well as identify unintended adverse effects of genome editing. Consolidating state of the art mouse models and expertise under a fee-for- service core, will broaden access to high quality testing data and accelerate the development of new therapeutics.

3。摘要 - 基因组编辑和生物学效应测试部分 BCM/水稻基因组的基因组编辑和生物效应测试部分（GE-BET）的目标编辑测试部分是为研究社区提供集中式，可访问的，费用的服务测试基因组编辑输送试剂和基因组编辑工具的资源。 Ge-Bets 将开发新方法和标准操作程序（SOP），并自定义基于分析的关于研究需求。 Ge-Bets利用Baylor的广泛的本地基因组编辑和测试经验来利用医学院（BCM）和赖斯大学，起源于BCM敲除老鼠表型项目，精密医学模型中心和NIH体细胞的BCM-RICE小动物测试中心基因组编辑程序。在这个项目中，Ge-Bets将开发用于测试基因组编辑试剂的管道在AIM 1中，我们将对荧光记者小鼠中的体细胞编辑系统进行测试。主要可交付成果包括生物分布，组织之间的编辑效率，细胞类型识别以及健康或毒性的变化来自基因组编辑和输送系统。在AIM 2中，我们将确定的效率，特异性和安全性相关疾病模型中的基因组编辑试剂。我们将评估下一代的内在和脱靶编辑在目标组织中进行测序以精确量化A的基因组编辑效率致病突变。编辑效率将与恢复或去除预期基因相关产品。这些研究将为新的治疗方法的可行性提供信息，并确定意外基因组编辑的不利影响。在收费下合并最先进的鼠标模型和专业知识服务核心，将扩大对高质量测试数据的访问，并加速新的开发疗法。