Structural characterization of antibody-responses following Zolgensma treatment for AAV capsid engineering to expand patient cohorts.

ABSTRACT: Monoclonal antibodies are useful tools to dissect the neutralizing antibody response against the adeno-associated virus (AAV) capsids that are used as gene therapy delivery vectors. The presence of pre-existing neutralizing antibodies in large portions of the human population poses a significant challenge for AAV-mediated gene therapy, primarily targeting the capsid leading to vector inactivation and loss of treatment efficacy. This study structurally characterizes the interactions of 21 human-derived neutralizing antibodies from three patients treated with the AAV9 vector, Zolgensma®, utilizing high-resolution cryo-electron microscopy. The antibodies bound to the 2-fold depression or the 3-fold protrusions do not conform to the icosahedral symmetry of the capsid, thus requiring localized

SUBMITTER: Mietzsch M 

PROVIDER: S-EPMC12009303 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature