Animal Model Production Section

项目概要动物模型制作核心 体细胞编辑联盟（SCGE）的总体目标是创建一个新的，整合的基因组 编辑工具，以加速这些方法的临床翻译。JAX基因编辑的目标 鼠标测试中心（JAX-GEMTC）是提供一个强大的，可扩展的平台的优化和 新编辑机器的资格认证。报告模型旨在检测不同类型的特异性和非特异性 特定的基因组编辑活动对于系统和有效地评价各种新的生物学特性是必不可少的。 设计用于靶向多种疾病相关细胞和组织的递送方法。的具体目标 该中心的动物模型生产组件的目的是生成和验证一套基因组- 编辑报告物小鼠线，其将说明用以下方法编辑修饰的效率、特异性和性质： 单细胞分辨率，并开发一个平台，为未来的报告线发展，以服务于目标 SCGE联盟成员。在我们现有的报告者模型的基础上，我们将创建一个报告者行面板 支持多个编辑器、编辑结果和脱靶活动的分析。穿过殖民地 管理和分配的努力，这些模型将有助于支持的目标， 测试的核心。我们的目标将通过三个具体目标实现：1）我们将产生鼠标 设计用于测试体细胞编辑效率和对多种类型编辑活性的特异性的报告细胞系， 包括NHEJ介导的indel，HR，碱基编辑和脱靶活性;我们将评估每一个的功能。 体内报告基因线，以确保其作为新递送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联盟的合作。为了实现这一点， 我们将验证和实施一种新的重组酶介导的盒式交换（RMCE）平台， 大型报告基因构建体的靶向效率，并将与SCGE合作开发报告基因模型 评估Aim 1中生成的行面板未捕获的新编辑器功能。

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.