On July 5th, 2024, Liu Shuai, Professor Zhen Gu and Professor Yuan Ping from CPS-ZJU jointly studied the Reformulating lipid nanoparticles for organ-targeted mRNA accumulation and accumulation The latest research results of translation were published in the internationally renowned journal Nature Communications. In this study, the authors achieved comprehensive organ-targeted mRNA delivery through the dual innovation of lipid structure and LNP formulation, which is expected to be applied to mRNA precision therapy.

Comprehensive targeted mRNA delivery requires both targeted mRNA distribution and targeted translation. Traditional LNP consists of ionizable cationic lipids, phospholipids, cholesterol and pegylated lipids. The presence of cholesterol helps LNP to adsorb lipoproteins in the blood and further bind to lipoprotein receptors in hepatocytes, thereby aggregating LNP in the liver. Therefore, it is difficult for current organ-targeted LNP to achieve targeted accumulation of extrahepatic mRNA. In this study, the fixed components (cholesterol and phospholipids) of LNP were removed, and the newly designed degradable cationic lipids were combined with quaternary ammonium lipids and pegylated lipids to form a three-component LNP, which successfully realized the lung targeted mRNA distribution and translation. Then, with the newly designed degradable cationic lipid as the core, traditional four-component LNP was constructed to realize the distribution and translation of hepato-targeted mRNA. This organ-targeting strategy can be extended to other cationic lipids and LNP systems. These results provide a new idea and a new standard for comprehensive organ-targeted mRNA delivery.