Complement Activation by Adeno-Associated Virus-Neutralizing Antibody Complexes.

ABSTRACT: Treatment of monogenetic disorders using vectors based on adeno-associated virus (AAV) is an area of intense interest. AAV is non-pathogenic human virus, and preexisting capsid antibodies are prevalent in the population posing a challenge to the safety and efficacy of AAV-mediated gene therapies. In this study, we investigated the risk of AAV-mediated complement activation when sera from a cohort of human donors were exposed to AAV9 capsid. Seropositive donor sera carrying neutralizing antibodies from a previous environmental exposure activated complement when admixed with AAV9 capsids and complement activation was associated with donors who had higher levels of anti-AAV IgG1 antibodies. These findings were consistent with mass spectrometry analysis that identified increased binding of imm

SUBMITTER: West C 

PROVIDER: S-EPMC10282828 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature