The evolving landscape of mRNA-LNP medicine: advances, challenges and future perspectives

Messenger RNA lipid nanoparticle (mRNA-LNP) technology has developed from a successful pandemic vaccine platform into a versatile therapeutic approach applicable to infectious diseases, oncology, autoimmune disorders, rare genetic diseases, tissue regeneration, and beyond. This review focuses on the conceptual evolution of mRNA-LNP systems, highlighting their transition from vaccine delivery vehicles toward in vivo cell reprogramming tools that support in situ chimeric antigen receptor T-cell (CAR-T) generation and targeted immune regulation. Advances in rational LNP design and RNA engineering have improved tissue-specific delivery and extended protein expression, broadening the clinical potential of this technology. Notably, a series of mRNA-LNP medicines have been approved or advanced to Phase III clinical trials, demonstrating substantial translational progress. However, challenges remain, including immunogenicity, repeat-dose safety, manufacturing scalability, and off-target effects. The future development of mRNA-LNP medicine is expected to be driven by artificial intelligence (AI)-guided molecular design, controllable expression systems, and personalized therapeutic applications. This article presents a unified view of the progress and trajectory of mRNA-LNP technology as a transformative therapeutic platform.