Targeted AAV gene therapy for neuroblastoma via direct capsid-antibody coupling

ABSTRACT: Adeno-associated viral (AAV) vectors are widely used in gene therapy for their versatility and safety, but their broad tropism limits cell-specific applications such as targeting primary or metastatic tumor cells. To address this, we developed AAV-STITCH, a strategy using SpyTag technology to covalently attach polypeptides to the AAV capsid. This allows precise, dose-dependent coupling of an anti-GD2 scFv to a galactose-binding-deficient AAV9-W503A capsid, redirecting tropism specifically to GD2-expressing neuroblastoma (NB) cells. In pseudometastatic xenograft mouse models, AAV-STITCHαGD2 selectively transduced NB tumor cells without transduction of healthy liver tissue. Furthermore, delivery of a suicide gene via AAV-STITCHαGD2 significantly slowed tumor growth and extended survival in m

SUBMITTER: Vania Broccoli 

PROVIDER: S-SCDT-10_1038-S44321-026-00520-7 | biostudies-other |

REPOSITORIES: biostudies-other