Structural and Biophysical Analysis of Adeno-Associated Virus Serotype 2 Capsid Assembly Variants
Antonette Bennett, Joseph Gargas, Austin Kansol, Jordyn Lewis, Jane Hsi, Joshua A. Hull, Mario Mietzsch, Lawrence J. Tartaglia, Nicholas Muzyczka, Nilakshee Bhattacharya, Paul R. Chipman, Mavis Agbandje‐McKenna, Robert McKenna
Abstract
Adeno-associated viruses (AAVs) have been shown to be useful vectors for gene therapy applications. Consequently, AAV has been approved as a biologic for the treatment of several monogenic disorders, and many additional clinical trials are ongoing. These successes have generated significant interest in all aspects of the basic biology of AAV. However, to date, there are limited data available on the importance of the capsid viral protein (VP) symmetry-related interactions required to assemble and maintain the stability of the AAV capsids and the infectivity of the AAV capsids. Characterizing the residue type and interactions at these symmetry-driven assembly interfaces of AAV2 has provided the foundation for understanding their role in AAV vectors (serotypes and engineered chimeras) and has determined the residues or regions of the capsid that can or cannot tolerate alterations.