On the mechanism of tissue-specific mRNA delivery by selective organ targeting nanoparticles

作者：Sean A. Dilliard, Qiang Cheng, Daniel J. Siegwart · 发表于：Proceedings of the National Academy of Sciences · 年份：2021 · DOI：10.1073/pnas.2109256118 · 被引用次数：993 · 研究领域：RNA Interference and Gene Delivery、SARS-CoV-2 and COVID-19 Research、Lipid Membrane Structure and Behavior

, and serum protein interactions of SORT nanoparticles. Additionally, we provide evidence for an endogenous targeting mechanism whereby organ targeting occurs via 1) desorption of poly(ethylene glycol) lipids from the LNP surface, 2) binding of distinct proteins to the nanoparticle surface because of recognition of exposed SORT molecules, and 3) subsequent interactions between surface-bound proteins and cognate receptors highly expressed in specific tissues. These findings establish a crucial link between the molecular composition of SORT nanoparticles and their unique and precise organ-targeting properties and suggest that the recruitment of specific proteins to a nanoparticle's surface can enable drug delivery beyond the liver.