CRISPR-Guided RNA Nanostructures for Targeted mRNA Delivery in Solid Tumors

Messenger RNA therapeutics require efficient and selective delivery systems to overcome tumor heterogeneity and immunosuppressive microenvironments. We engineer CRISPR-guided RNA nanostructures (CRISPR-RNPs) that exploit guide RNA-target complementarity for tumor-selective mRNA delivery. CRISPR-RNPs achieve 94% transfection efficiency in MCF-7 breast cancer cells with minimal off-target effects (<3% in co-cultured normal cells). Cargo mRNA encoding proapoptotic BAX protein induces 78% tumor cell apoptosis in vitro. In vivo mouse xenograft experiments demonstrate 78% tumor volume reduction versus untargeted controls (p<0.001), with favorable pharmacokinetics and no systemic toxicity at therapeutic doses. These results establish CRISPR-guided RNA nanostructures as a promising platform for precision cancer mRNA therapy.