Gene Therapy for Urea Cycle Disorders

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DESCRIPTION (provided by applicant): The goal of this application is to develop an effective gene therapy for ornithine transcarbamylase (OTC) deficiency. Studies begin with the development of an optimal AAV vector called the "clinical candidate" in Project I. Additional studies will be performed in this project to evaluate potential immunologic barriers to successful liver directed gene therapy. The clinical candidate will be evaluated for safety and efficacy in OTC deficient mice and nonhuman primates in Project II. The molecular state of the vector genome and its potential oncogenicity will be studied in Project III. Cores for vector production, cell morphology, animal models, and administration will provide support to the projects. An External Scientific Advisory Committee and an Ethics Advisory Board will be convened to provide advice to the program leadership. At the completion of this four year program, the investigators hope to provide an AAV vector with preclinical data to support its translation into humans.