Innovative Translational Imaging Technologies to Monitor Genome Edited Cells in Vivo

项目摘要/摘要 本申请是根据RFA-RM-18-025号文件提交的，该文件的重点是开发新的 非侵入性标记和监测体内基因组编辑细胞的技术。我们提交的材料符合 目的通过建立全身正电子发射断层扫描(PET)成像的新领域来实现RFA的目的 体细胞基因组编辑，以及支持翻译所需的定量方法。这 应用程序以经过验证的创新工具、技术和资源的基础设施为基础，并且高度 经验丰富的多学科调查团队。研究将达到顶峰，为体外翻译工具 用于监测基因组编辑细胞的设计(模体、定量测量)和体内方法 为未来治疗人类疾病的器官系统的临床研究提供信息。UH2相 将重点放在用原型模型中编辑的细胞进行体外和体内定量测试(具体目标1)。这个 这些研究中的活动可以适应任何细胞类型或器官系统。UH3阶段将解决 体内检测效率和安全性评估，包括动物免疫反应的可能性 采用定量成像分析和相关工具进行翻译的模型(具体目标2)。总的来说， 这些研究将建立一个用于监测安全性和有效性的全身PET成像的新领域 并将贡献新的知识，导致未来精心设计的临床前 研究和人体临床试验。

PROJECT SUMMARY / ABSTRACT This application is submitted in response to RFA-RM-18-025, which is focused on the development of new technologies to noninvasively label and monitor genome-edited cells in vivo. Our submission meets the objective of the RFA by establishing a new field of total-body positron emission tomography (PET) imaging for somatic cell genome editing, and with quantitative methodologies needed to support translation. This application is grounded in a proven infrastructure of innovative tools, technologies, and resources, and a highly accomplished multidisciplinary team of investigators. Studies will culminate in translational tools for the in vitro design (phantoms, quantitative measures) and in vivo methods for monitoring genome-edited cells that will inform future clinical investigations across organ systems for the treatment of human disease. The UH2 phase will focus on in vitro and in vivo quantitative testing with edited cells in prototype models (Specific Aim 1). The activities in these studies can be adapted to any cell type or organ system. The UH3 phase will address detection efficiency and safety assessments in vivo, including the potential for immune responses in an animal model that employs quantitative imaging analysis and related tools for translation (Specific Aim 2). Overall, these investigations will establish a new field of total-body PET imaging for monitoring the safety and efficiency of somatic cell genome editing and will contribute new knowledge that leads to future well-designed preclinical studies and human clinical trials.