{"id":"doi:10.1038/s44321-026-00520-7","kind":"article","title":"Targeted AAV gene therapy for neuroblastoma via direct capsid-antibody coupling","authors":["Luoni M","Parracino S","Giannelli SG","Morosi F","Ventura E","Di Pizio A","Muggeo S","Iannielli A","Sicardi S","Canu T","Russo T","Esposito A","Del Carro U","Pastorino F","Broccoli V"],"author_count":15,"year":2026,"published":"2026-09-12","venue":"EMBO molecular medicine","cited_by":0,"doi":"10.1038/s44321-026-00520-7","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1038/s44321-026-00520-7","archive_url":"https://space-kitty.com/papers/doi:10.1038/s44321-026-00520-7","updated":null,"pmid":"42732029","pmcid":"PMC13658805","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC13658805/pdf","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 mice with subcutaneous and pseudometastatic NB xenografts. When combined with standard-of-care chemotherapy for relapsed NB, AAV-STITCHαGD2 produced robust curative effects. Collectively, these results demonstrate the feasibility of engineering AAVs with highly specific transduction properties, providing a versatile platform for targeted tumor cell suppression and advancing the development of next-generation, precision gene therapies for cancer.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Targeted AAV gene therapy for neuroblastoma via direct capsid-antibody coupling\" by Luoni M, Parracino S, Giannelli SG et al., https://doi.org/10.1038/s44321-026-00520-7, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"gene-cell-therapy","name":"Gene & Cell Therapy","domain_slug":"medicine"}],"cited_in_dossiers":[]}