MANUFACTURING OF PLASMID AND VECTOR AND GLP DOSE-ESCALATION TOXICOLOGY STUDIES IN NORMAL RATS AND NORMAL NHPS

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Currently, the National Institute of Neurological Disorders and Stroke (NINDS), via its URGenT network, is funding a cooperative agreement for the manufacturing of an AAV9/AGA vector, plasmids, and GLP dose-escalating studies as a potential therapy the severe and progressive genetic neurological disorder, Aspartylglucosaminuria (AGU). The goals of the URGenT cooperative agreement are to manufacture the AAV9/AGA vector, the vector ITR plasmid containing the AGA gene, and the packaging/helper plasmids pAAV9 and pALD-X80 (which provide the AAV and Adenoviral helper functions needed for AAV vector production in mammalian cell culture, respectively). For the AAV9/AGA vector manufacturing, the URGenT network will manufacture the vector using a manufacturing process similar to that utilized by the Translational Gene Therapy Core that produces AAV9/AGA with comparable quality attributes. Specifics of the process will come during the tech transfer described in the base task. The final product qualification and characterization testing will include assays of sterility, endotoxin, purity, identity, activity/potency, vector genome titer, capsid particle titer, appearance, and genomic structure. Upon establishment of the vectors, and optimal characterization, this project will progress to IND-enabling rat and NHP toxicology studies to support the IND.