Structurally Mapping Antigenic Epitopes of Adeno-associated Virus 9: Development of Antibody Escape Variants.

ABSTRACT: Adeno-associated viruses (AAV) serve as vectors for therapeutic gene delivery. AAV9 vectors have been FDA approved, as Zolgensma, for the treatment of spinal muscular atrophy and are being evaluated in clinical trials for the treatment of neurotropic and musculotropic diseases. A major hurdle for AAV-mediated gene delivery is the presence of preexisting neutralizing antibodies in 40 to 80% of the general population. These preexisting antibodies can reduce therapeutic efficacy through viral neutralization and the size of the patient cohort eligible for treatment. In this study, cryo-electron microscopy and image reconstruction were used to define the epitopes of five anti-AAV9 monoclonal antibodies (MAbs), ADK9, HL2368, HL2370, HL2372, and HL2374, on the capsid surface. Three of these, ADK9

SUBMITTER: Emmanuel SN 

PROVIDER: S-EPMC8827038 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature