Structural Study of Aavrh.10 Receptor and Antibody Interactions
Mario Mietzsch, Jennifer C. Yu, Jane Hsi, Paul Chipman, Felix Broecker, Zhang Fuming, Robert J. Linhardt, Peter H. Seeberger, Regine Heilbronn, Robert McKenna, Mavis Agbandje-McKenna
Abstract
Gene therapy vectors based on adeno-associated virus rhesus isolate 10 (AAVrh.10) have been used in several clinical trials to treat monogenetic diseases. However, compared to other AAV serotypes little is known about receptor binding and antigenicity of the AAVrh.10 capsid. Particularly, preexisting neutralizing antibodies against capsids are an important challenge that can hamper treatment efficiency. This study addresses both topics and identifies critical regions of the AAVrh.10 capsid for receptor and antibody binding. The insights gained were utilized to generate AAVrh.10 variants capable of evading known neutralizing antibodies. The findings of this study could further aid the utilization of AAVrh.10 vectors in clinical trials and help the approval of the subsequent biologics.