Research progress on lipid nanoparticle messenger RNA delivery system.

Abstract

mRNA therapeutic is a biotechnology that involves delivering in vitro transcribed mRNA into specific cells to produce target proteins for the treatment or prevention of diseases. However, the development of mRNA therapeutics relies largely on mRNA delivery systems, and lipid nanoparticles (LNPs) represent the most widely used mRNA carriers in clinical applications. Composed of ionizable lipids, phospholipids, cholesterol, and polyethylene glycol-lipids, LNPs can address critical challenges in mRNA drug development, such as poor in vivo stability and the difficulty in crossing biological barriers. Ultimately, LNPs enable safe, efficient, and targeted mRNA delivery to the liver, lung, spleen, and so on. This review outlines the roles of the four lipid components in LNPs for mRNA delivery. Then it introduces targeted mRNA delivery to various organs/tissues such as the liver, lung, spleen, pancreas, bone marrow, and placenta, using strategies of antibody modification, lipid structure alteration, and specialized administration routes. Additionally, this review discusses the applications and challenges of LNP-based mRNA therapeutics in disease treatment, aiming to provide insights for the clinical translation of mRNA therapies and the further innovation of LNP delivery systems.