Modified AAV5 capsid for improved brain biodistribution following direct injection in preclinical models.

ABSTRACT: Gene therapies based on adeno-associated virus vectors hold strong potential for the treatment of central nervous system disorders. However, systemic delivery is limited by the blood-brain barrier, off-target effects, immune responses, and vector loss. Direct intraparenchymal injections can bypass these barriers by targeting specific brain regions, but broader vector distribution is essential to reduce the need for multiple injections and to achieve widespread transgene expression. The brain biodistribution of adeno-associated virus serotype 5 is partially mediated by its interaction with sialic acid. Here, we describe a modified serotype 5 variant, AAV5neo, carrying a single amino acid substitution that alters its sialic acid-binding properties. In cultured cells, AAV5neo exhibits transdu

SUBMITTER: Kieper SN 

PROVIDER: S-EPMC12702006 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature