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

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.

Grant Number: 75N95022D00021-0-759502300003-1
NIH Institute/Center: NIH
Principal Investigator: Amanda Burnaugh