OFF-TARGET RESOURCE CORE

项目总结 非目标编辑分析对于我们的治疗线索的发展将是如此基础，无论 已治疗的疾病--苯丙酮尿症(主导项目1)、遗传性酪氨酸血症1型(项目2)或 粘多糖病I型(项目3)--这是最终出现的任何IND应用所不可或缺的 这些项目，我们正在提出一个脱离目标的资源核心，将服务于所有三个研究项目。 该资源核心将提供与临床前研究直接一致的服务，这些研究是 由美国食品和药物管理局(FDA)推荐的人类基因产业指南草案 结合人类基因组编辑的治疗产品，即：(1)靶上和靶外的识别 编辑活动，包括所有非目标编辑事件的类型、频率和位置，考虑到 人类遗传变异；(2)基因组完整性评估，包括染色体重排，大 插入或大量删除；以及(3)评估与非目标编辑相关的生物学后果。

PROJECT SUMMARY Off-target editing analyses will be so fundamental to the development of our therapeutic leads, regardless of the disease treated—whether phenylketonuria (Lead Project 1), hereditary tyrosinemia type 1 (Project 2), or mucopolysaccharidosis type I (Project 3)—and so integral to any IND applications that ultimately emerge from the Projects, that we are proposing an Off-Target Resource Core that will serve all three Research Projects. This Resource Core will provide services that are directly aligned with the preclinical studies that are recommended by the U.S. Food and Drug Administration (FDA) Draft Guidance for Industry on Human Gene Therapy Products Incorporating Human Genome Editing, namely: (1) identification of on-target and off-target editing activity, including the type, frequency, and location of all off-target editing events, taking into account human genetic variation; (2) assessment of genomic integrity, including chromosomal rearrangements, large insertions, or large deletions; and (3) evaluation of the biological consequences associated with off-target editing.