RNA vaccines in motion: A multidisciplinary exploration of design, delivery, and deployment

Abstract

RNA vaccines represent a major advance in prophylactic and therapeutic vaccinology, largely due to the success of nucleoside-modified mRNA vaccines encapsulated in lipid nanoparticles (LNPs) during the COVID-19 pandemic. These platforms build on long-standing progress in RNA chemistry, immunology, and nanotechnology. This review concentrates primarily on molecular design (codon/sequence optimization, chemical modifications, and data-driven antigen selection) and delivery optimization (LNPs and emerging alternatives like virus-like particles, extracellular vesicles, and ligand-targeted systems). Clinical progress is highlighted through examples from oncology, including personalized neoantigen approaches, combination therapies, and immunopeptidomics-guided validation, as well as early preclinical work on tolerance induction and localized protein replacement. Overall, continued refinement of RNA sequence engineering and delivery systems positions these platforms as flexible tools for rapid-response vaccination and therapy, especially where fast antigen adaptation and scalable production are required.