mRNA Lipid Nanoparticles for Cell Engineering in Vivo and in Vitro: Current Applications and Future Directions

ABSTRACT Messenger RNA‐lipid nanoparticles (mRNA‐LNPs) serve as a revolutionary platform, enabling precise and transient protein expression for both in vivo and in vitro cell engineering without genomic integration. Recent breakthroughs in mRNA design and LNP formulation have expanded their applications across immunotherapy, regenerative medicine, and genome editing. However, challenges such as off‐target delivery, immunogenicity, and inadequate organ‐specific targeting limit their broader therapeutic utility. This review systematically elaborates the design principles of mRNA‐LNPs, including mRNA structural elements and functional lipid components that facilitate endosomal escape. It summarizes recent advances in their applications for cell engineering, both ex vivo and in vivo. Key challenges related to delivery precision and immunogenicity are thoroughly analyzed, alongside strategies to improve targeting through administration routes, surface modifications, and endogenous targeting mechanisms. The article also outlines main directions for developing next‐generation mRNA‐LNPs. Overall, this review will support further research on mRNA‐LNPs and promote their clinical translation in the field of cell engineering.