Dual-vector nanoengineered mRNA-CRISPR delivery systems for precision gene therapy in choroidal melanoma

Choroidal melanoma is the most common primary intraocular malignancy, and effective gene therapy remains limited by ocular barriers, tumor heterogeneity, and inefficient nucleic acid delivery. This review critically analyses the molecular rationale, engineering principles, emerging nanoarchitectures, biological validation, and translational prospects of dual-vector nanoengineered mRNA-CRISPR delivery systems for precision gene therapy in choroidal melanoma. The manuscript also highlights key challenges and future strategies for clinical implementation. Current evidence indicates that dual-vector platforms enable independent optimization of mRNA and CRISPR cargos while maintaining coordinated spatiotemporal therapeutic activity. We conducted a literature search in PubMed, Scopus, and Web of Science for relevant studies published from January 2015 to September 2026. Functional cargo partitioning, vector modularity, programmable intracellular trafficking, and ocular-targeted nanoengineering improve delivery precision and reduce biological compromise associated with co-encapsulation. Lipid, polymeric, hybrid, biomimetic, and viral-nonviral architectures each provide distinct engineering advantages depending on therapeutic objectives. Preclinical studies support enhanced genome editing, transient protein restoration, improved tumor suppression, and reduced off-target effects. Nevertheless, manufacturing scalability, regulatory standardization, long-term safety, and clinical validation remain major barriers to translation. Dual-vector nanoengineered mRNA-CRISPR systems represent a promising next-generation platform for precision gene therapy in choroidal melanoma by enabling coordinated and programmable therapeutic delivery. Continued advances in modular nanoengineering, personalized cargo selection, and clinically scalable manufacturing will be essential for successful translation into precision ocular oncology.