Animal Model Production Section

项目总结动物模型制作核心 体细胞编辑联盟(SCGE)的总体目标是创建一组新的、完整的基因组 编辑工具，以加速将这些方法转换到临床。JAX基因编辑的目标 鼠标测试中心(JAX-GEMTC)是为了提供一个健壮、可扩展的平台进行优化和 新编辑机构的认证。报警器型号专为检测不同类型的特定和非 特定的基因组编辑活动对于系统和有效地评价各种小说是必不可少的 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 该中心的动物模型制作部分将生成并验证一套基因组- 编辑报告鼠标行，以说明使用编辑修改的效率、特异性和性质 单细胞分辨率，并为未来的记者线发展开发一个平台，以服务于 SCGE联盟成员。在我们现有的记者模型的基础上，我们将创建一组记者专线 支持多个编辑者的分析、编辑结果和脱离目标的活动。通过蜂群 资源核心的管理和分配工作，这些模型将用于支持以下目标 测试核心。我们的目标将通过三个具体目标来实现：1)我们将生成鼠标 设计用于测试多种类型编辑活动的体细胞编辑效率和特异性的报道线， 包括NHEJ中介的INDELS、HR、基础编辑和非目标活动；我们将评估每一个的功能 在体内进行记者专线，以确保其作为新交付技术的测试平台的实用性；3)开发和 部署平台和模型以支持未来与SCGE联盟的协作。要做到这一点， 我们将验证并实现一个新的重组酶介导的盒式磁带交换(RMCE)平台，以改进 大型记者的目标定位效率构建，并将与SCGE合作开发记者模式 评估未被目标1中产生的线条面板捕获的新颖的编辑功能。

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.