Authors
Mirko Luoni, Stefano Parracino, Serena G Giannelli, Francesca Morosi, Elisa Ventura, Agostina Di Pizio, Sharon Muggeo, Angelo Iannielli, Silvia Sicardi, Tamara Canu, Tommaso Russo, Antonio Esposito, Ubaldo Del Carro, Fabio Pastorino, Vania Broccoli
Published in
EMBO molecular medicine. Sep 12, 2026. Epub Sep 12, 2026.
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.
PMID:
42732029
Bibliographic data and abstract were imported from PubMed on 13 Sep 2026.
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