Afsane Radmand, Hyejin Kim, Jared Beyersdorf, Curtis N Dobrowolski, Ryan Zenhausern, Kalina Paunovska, Sebastian G Huayamares, Xuanwen Hua, Keyi Han, David Loughrey, Marine Z C Hatit, Ada Del Cid, Huanzhen Ni, Aram Shajii, Andrea Li, Abinaya Muralidharan, Hannah E Peck, Karen E Tiegreen, Shu Jia, Philip J Santangelo, James E Dahlman
Adding a cationic helper lipid to a lipid nanoparticle (LNP) can increase lung delivery and decrease liver delivery. However, it remains unclear whether charge-dependent tropism is universal or, alternatively, whether it depends on the component that is charged. Here, we report evidence that cationic cholesterol-dependent tropism can differ from cationic helper lipid-dependent tropism. By testing how 196 LNPs delivered mRNA to 22 cell types, we found that charged cholesterols led to a different lung:liver delivery ratio than charged helper lipids...
March 12, 2024: Proceedings of the National Academy of Sciences of the United States of America