Viral Vector and Regulatory Core

项目摘要病毒载体和调控核心 将实验室发现转化为临床试验会产生许多管理和监管挑战。 基因编辑带来了更多的安全问题，例如非目标编辑的不利后果， 这需要创造力和经验，以便根据需要进行适当的调查、量化和缓解。病毒载体 而Regulatory Core将U19团队成员的必要专业知识和协作历史带到 为该U19提供两项关键服务：规模化生产所有AAV载体，以确保始终如一的高质量 这些生物试剂用于项目中的治疗测试；以及实际指导和支持，以帮助 项目通过监管途径提交IND。主要创新包括访问可扩展的 AAV9的制造系统可通过UTSW的翻译基因治疗核心获得，这是 由病毒载体和监管核心导演史蒂文·格雷执导。AAV产品质量和质量的连续性 通过翻译基因治疗核心提供的效力将简化监管过程并避免 昂贵且耗时的搭桥研究。核心团队开发的第二项创新是临床前 以及用于传递非自身转基因的临床免疫管理方案。因为任何基于基因编辑的 通过此计划开发的治疗方案应被接受者的免疫系统视为非我 系统，这些策略的结合可能是临床前和临床成功的关键。关 与基因组编辑核心就基因组编辑结果的载体设计和解释进行接触，以及 以临床前小鼠模型为核心进行研究设计，以确保所有评估与IND保持一致 要求，将彻底编织进管道，优化效率。实现病毒传播的途径 向量和监管核心的目标将利用基于核心领导经验的最佳实践， 支持工作人员和顾问，已成功提交了许多预审和IND申请 以AAV为基础的疗法。核心的意义在于它将确保项目中的所有活动和 其他核心符合FDA的质量预期，并将主动工作，以避免不必要的延迟或工作 重复以满足这些期望。这对该U19计划的总体目标至关重要， 特别是对于没有经过翻译过程的研究实验室。具体目标是：1) 通过提供AAV载体支持U19项目；2)召开InterAct会议以了解FDA 对牵头项目治疗实体的临床前概念验证数据的期望；3)进行B型 参加IND前会议并协调支持IND的研究；以及4)协调缔约方汇编和提交 允许的增量。

PROJECT SUMMARY VIRAL VECTOR AND REGULATORY CORE Translation of a laboratory discovery to a clinical trial generates many management and regulatory challenges. Gene editing brings additional safety issues to the fore, such as the adverse consequences of off-target editing, that require creativity and experience to properly investigate, quantify, and mitigate as needed. The Viral Vector and Regulatory Core brings the necessary expertise and history of collaboration across U19 team members to offer two critical services to this U19: scaled production of all AAV vectors to ensure consistently high quality of these biological reagents for therapeutic testing in the projects; and practical guidance and support to help the projects navigate the regulatory path to an IND submission. Key innovations include access to a scalable manufacturing system for AAV9 available through the Translational Gene Therapy Core at UTSW, which is directed by the Viral Vector and Regulatory Core Lead Steven Gray. The continuity of AAV product quality and potency offered through the Translational Gene Therapy Core will streamline the regulatory process and avoid costly and time-consuming bridging studies. A second innovation developed by the Core team are preclinical and clinical immune-management protocols for delivery of non-self transgenes. Since any gene editing–based treatment developed through this Program is expected to be viewed as non-self by the recipient's immune system, incorporation of these strategies is likely to be critical for the preclinical and clinical success. Close engagement with the Genome Editing Core on vector design and interpretation of genome editing results, and with the Preclinical Mouse Model Core on study design to assure all assessments are aligned with IND requirements, will be thoroughly woven into the pipeline to optimize efficiency. The approach to achieve the Viral Vector and Regulatory Core's goals will leverage best practices based on the experience of the Core Lead, supporting staff and consultants that have resulted in numerous successful pre-IND and IND submissions for AAV-based therapeutics. The significance of the Core is that it will ensure that all activities in the projects and other cores meet FDA quality expectations, and will work proactively to avoid unnecessary delays or work repetition to meet those expectations. This is central to the overall aims of this U19 Program and is critical, particularly for research labs that have not gone through the translational process. The Specific Aims are: 1) To support the U19 projects by supplying AAV vectors; 2) To conduct an INTERACT meeting to understand FDA expectations for pre-clinical proof of concept data of the lead project therapeutic entity; 3) To conduct a type B pre-IND meeting and coordinate IND-enabling studies; and 4) To coordinate parties to assemble and submit an allowable IND.