ArticleEMBO molecular medicine2026
Targeted AAV gene therapy for neuroblastoma via direct capsid-antibody coupling.
Article in EMBO molecular medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Authors and funding
15 authors.
Funding
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.
Identifiers
42732029What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.