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Gene Therapy Strategies for Uveal Melanoma: Adeno-associated Virus Delivery Challenges and Translational Opportunities
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DOI：10.1007/s40259-026-00794-w.png)
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Abstract
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Uveal melanoma is the most common primary intraocular malignancy in adults and remains associated with poor outcomes once metastatic disease develops. Despite advances in local tumour control and molecular prognostication, effective systemic therapies capable of delivering durable benefit are limited. A range of gene-based therapeutic strategies have been explored in uveal melanoma, including immune-based approaches, gene-modified cell therapies and direct gene delivery. While these strategies have yielded important biological insights and modest clinical advances, their broader impact has been constrained by challenges related to delivery, tumour specificity, durability of effect and translational feasibility. This review surveys the current landscape of gene-based therapies investigated in uveal melanoma and synthesises lessons learned from these approaches, with a particular emphasis on the delivery platform as a determinant of therapeutic success. We examine the emerging potential of adeno-associated virus vectors as gene-delivery platforms for uveal melanoma, drawing on their safety profile and capacity for sustained transgene expression. We highlight the need for adaptation beyond native adeno-associated virus serotypes and discuss advances in capsid engineering, targeting strategies and control mechanisms that enable tumour-selective gene delivery. Finally, we consider translational challenges and future directions for integrating targeted adeno-associated virus-based approaches into therapeutic strategies for uveal melanoma.
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