mRNA-LNP vaccines: rational design, delivery optimization, and clinical translation

) to modulate immune responses and enable organ targeting; and (3) LNP surface functionalization (with small molecules, peptides, and antibodies) for precise specific cell or organ targeting. Although multiple candidate vaccines for infectious disease prevention and cancer treatment have entered clinical trials, their clinical translation is still limited by insufficient targeting accuracy, potential immunogenicity and toxicity, and the challenge of universal delivery systems. Future breakthroughs require the integration of multidisciplinary innovations, focusing on the development of degradable lipids and novel targeting ligands to improve delivery precision, the application of more biocompatible polymers (such as pSar and POx) to replace PEG to enhance safety, and the use of artificial intelligence (AI) to accelerate LNP formulation design and performance prediction. This review summarizes the key optimization strategies and clinical progress and explores future directions to overcome the existing bottlenecks and promote mRNA-LNP technology as the cornerstone of next-generation precision medicine.