Animal Model Production Section

动物模型制作科

• 批准号: 10450129
• 负责人: Stephen A Murray
• 金额: $ 4.43万
• 依托单位: JACKSON LABORATORY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-18 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10450129
• 关键词: Acute; Alleles; Alzheimer' s Disease; Alzheimer' s disease model; Animal Model; CRISPR/Cas technology; Cells; Clinic; Collaborations; Credentialing; Development; Disease; Engineering; Evaluation; Event; Foundations; Future; Generations; Genes; Genetic Engineering; Goals; In Situ; Knockout Mice; Laboratories; Light; Mediating; Modeling; Modification; Molecular; Molecular Analysis; Mus; Nature; Nonhomologous DNA End Joining; Outcome; Phenotype; Process; Production; Reporter; Research; Research Personnel; Resolution; Science; Services; Somatic Cell; Specificity; System; Technology; Testing; The Jackson Laboratory; Tissues; Translations; United States National Institutes of Health; Visualization; Work; base; base editing; cell type; clinical application; design; experience; gene therapy; genetic resource; genome editing; homologous recombination; human disease; improved; in vivo; insertion/deletion mutation; member; model design; mouse model; next generation; novel; precision genetics; programs; recombinase-mediated cassette exchange; serial imaging; somatic cell gene editing; tool

PROJECT SUMMARY ANIMAL MODEL PRODUCTION CORE The overall goal of the Somatic Cell Editing Consortium (SCGE) is to create a novel, integrated set of genome editing tools to accelerate translation of these approaches to the clinic. The goal of the JAX Gene Editing Mouse Testing Center (JAX-GEMTC) is to provide a robust, scalable platform for the optimization and credentialing of new editing machinery. Reporter models designed to detect different types of specific and non- specific genome-editing activity are essential for the systematic and efficient evaluation of a variety of novel delivery approaches designed to target a diverse array of disease-relevant cells and tissues. The specific goals of the Animal Model Production component of this Center are to generate and validate a suite of genome- editing reporter mouse lines that will illustrate the efficiency, specificity, and nature of editing modifications with single-cell resolution, and to develop a platform for future reporter line development to serve the goals of SCGE consortium members. Building on our existing reporter model, we will create a panel of reporter lines that support analysis of multiple editors, editing outcomes, and off-target activity. Through the colony management and distribution effort of the RESOURCE CORE, these models will serve to support the goals of the TESTING CORE. Our goals will be achieved through three Specific Aims: 1) We will generate mouse reporter lines designed to test somatic cell editing efficiency and specificity for multiple types of editing activity, including NHEJ-mediated indels, HR, base editing, and off-target activity; We will assess the function of each reporter line in vivo to assure its utility as a test platform for new delivery technologies; 3) To develop and deploy platforms and models to support future collaborations with the SCGE consortium. To accomplish this, we will validate and implement a novel recombinase-mediated cassette exchange (RMCE) platform to improve the efficiency of targeting of large reporter constructs, and will work with the SCGE to develop reporter models that assess novel editor functions not captured by the panel of lines produced in Aim 1.

项目摘要动物模型生产核心 体细胞编辑联盟（SCGE）的总体目标是创建一个新颖的，集成的基因组集 编辑工具以加速这些方法到诊所的翻译。 JAX基因编辑的目标 鼠标测试中心（JAX-GEMTC）是为优化提供一个可靠的可扩展平台 新编辑机械的证书。旨在检测不同类型的特定和非 - 的记者模型 特定的基因组编辑活动对于对各种新型的系统和有效评估至关重要 旨在针对各种与疾病相关的细胞和组织的递送方法。具体目标 该中心的动物模型生产成分的生成和验证一套基因组 - 编辑记者鼠标线条，以说明使用编辑修改的效率，特异性和性质 单细胞解决方案，并为未来的记者线开发开发一个平台，以实现 SCGE财团会员。在现有的记者模型的基础上，我们将创建一个记者线的小组 支持对多个编辑者，编辑结果和脱离目标活动的分析。通过殖民地 资源核心的管理和分配工作，这些模型将有助于支持目标 测试核心。我们的目标将通过三个特定目标实现：1）我们将生成鼠标 旨在测试多种类型编辑活动的体细胞编辑效率和特异性的记者线条， 包括NHEJ介导的Indels，人力资源，基础编辑和非目标活动；我们将评估每个功能 在Vivo中，记者线确保其用作新交付技术的测试平台； 3）发展和 部署平台和模型，以支持与SCGE财团的未来合作。为此， 我们将验证并实施一种新型的重组酶介导的盒式盒式交易所（RMCE）平台，以改善 针对大型记者结构的效率，并将与SCGE合作开发记者模型 该评估的新编辑器功能未由AIM 1中产生的线条小组捕获。