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Targeted and efficient AAV therapy for neuroblastoma via direct capsid-antibody coupling

Luoni, M.; Giannelli, S. G.; Parracino, S.; Morosi, F.; Ventura, E.; Di Pizio, A.; Muggeo, S.; Iannielli, A.; Canu, T.; Russo, T.; Antonio, E.; Pastorino, F.; Broccoli, V.

2025-11-13 bioengineering
10.1101/2025.11.12.687993 bioRxiv
Show 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-STITCHGD2 selectively transduced NB tumor cells without transduction of healthy tissues. Furthermore, delivery of a suicide gene via AAV-STITCHGD2 suppressed tumor growth and extended survival in mice with subcutaneous and pseudometastatic NB xenografts. These findings establish the feasibility of engineering AAVs with cell-type-specific transduction properties, providing a powerful and adaptable platform for the selective elimination of NB tumor cells. This technology marks a meaningful advance toward next-generation, targeted cancer therapies with strong clinical potential.

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"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.