- Core 2 The goal of the Therapeutic Viral Vector Design and Development Core (Core2) is to guide viral vector design, produce high quality viral vectors, and support Investigator initiated product development for novel vector based biologics with the goal of moving them to an IND. Significantly, the services of the Vector D & D Core represent a fundamental necessity to the defined and developmental projects within this CORT application as well as the larger identified Research Base. The center now holds 6 INDs for AAV gene therapy in various muscular dystrophies. We have gained valuable experience through our interactions with the FDA regarding the preclinical and toxicology/biodistribution studies required for IND approval. As part of this Core, Dr. Rodino-Klapac and her team will provide guidance for each project on the proper design of viral vectors and implementation of IND enabling preclinical studies. Understanding the translational pathway facilitates coordination between the PI's research team and the Vector Core for the production and testing of rAAV and other viral vectors in a manner consistent with FDA expectations at all phases of product development. This translates into a uniform vector product as a result of using consistent processes from early pre-clinical preps, through tox vector generation and ultimately early phase clinical grade vector produced using phase appropriate cGMPs. Through the demonstrated support of the Research Base within the Center for Gene Therapy at NCH and outside external collaborations, the NCH Vector Core has garnered such experience. The infrastructure support supplied by this P50 mechanism will allow for production of pre-clinical grade vectors for the three projects as well as guidance on vector design and preclinical implementation for each project in addition to the defined Research Base. Moreover, continued refinement of critical production processes and test methods as well as feasibility testing of novel AAV vector modalities will provide greater value to research base Investigators by reducing cost and time to completion with better quality and enhanced capacity.
Our Specific Aims build upon the existing Vector Core infrastructure at NCH and will fulfill the primary goal of this CORT application - to accelerate the translation of basic science projects into genetic therapies for muscular dystrophies. In summary, direct interaction between the Core and Investigative team from each of the three projects will leverage product and regulatory experience to accelerate timelines for defined products and provide guidance where it was lacking to enable new laboratories to move proof of concept studies rapidly into translational research. The ultimate effect of this aligns perfectly with P50 CORT program mission, which includes the development of ?tangible products or deliverables? for the ?development of more effective treatments? for human disease in which case we will putting more novel biologics into the clinical trial pipeline for treatment of a host of musculoskeletal diseases.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Specialized Center (P50)
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Special Emphasis Panel (ZAR1)
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Nationwide Children's Hospital
United States
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