mRNA therapeutics in cancer: from molecular design to clinical translation

Messenger RNA (mRNA) therapeutics have evolved from a technically constrained modality into a clinically validated platform for vaccination that is increasingly being explored in oncology. The field is no longer defined by whether mRNA can encode therapeutic proteins, but by how RNA expression can be controlled across spatial, dose, duration, and immune context to achieve therapeutic benefit. This review frames mRNA cancer therapeutics as integrated programmable systems that link RNA architecture, delivery technologies, payload pharmacology, immune interactions, manufacturing and clinical translation. We discuss major mRNA modalities and examine lipid nanoparticles together with emerging delivery platforms, with particular attention to extrahepatic targeting, endosomal escape, repeat dosing, and cell-type specificity. We then summarize the clinical landscape of mRNA-based cancer therapies, including universal and personalized vaccines, encoded antibodies and bispecifics, cytokines and immune modulators, and ex vivo and in vivo cell-engineering strategies. Across these applications, key design constraints include balancing transgene expression with immune activation, controlling local versus systemic activity, ensuring targeting specificity, and optimizing antigen selection and presentation. We propose that mRNA cancer therapeutics are diverging into modality-specific solutions in which clinical efficacy depends on coordinated optimization of RNA engineering, productive delivery, payload pharmacology, and tumor-immune biology.