Principles of lipid nanoparticle design for mRNA delivery

Abstract mRNA therapeutics have significantly evolved within the life sciences, particularly in applications such as vaccines, tumor immunotherapy, protein replacement, gene editing, and monoclonal antibody therapy. To fully realize the potential of mRNA drugs and mitigate the adverse effects, substantial vector materials have been developed for delivery of these pharmaceutical agents. Lipid nanoparticles (LNPs) represent the most clinically advanced mRNA carriers, recognized by U.S. Food and Drug Administration approved mRNA vaccines and numerous clinical trials. Diverse therapeutic applications necessitate tailored design of LNPs. Herein, we outline the principles of LNP design for mRNA delivery, focusing specifically on their effectiveness, targeting capabilities, safety profiles, and nanoparticle stability. Additionally, we present the latest advancements in mRNA‐LNP technology. This review aims to elucidate the benefits and design principles of LNP delivery systems for mRNA therapeutics, providing insights into breakthroughs and innovative ideas for further enhancing these advantages. These summaries are dedicated to promoting the broader applications of LNP‐mRNA drugs, aiming to advance the treatment of serious diseases in an effective and safe manner.