Viral Vector and Regulatory Core

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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.