Lipid nanoparticle mRNA systems containing high levels of sphingomyelin engender higher protein expression in hepatic and extra-hepatic tissues
Nisha Chander, Genc Basha, Miffy H. Y. Cheng, Dominik Witzigmann, Pieter R. Cullis
Abstract
compared with systems containing 10 mol % DSPC or ESM. When injected i.v., LNP mRNAs containing 40 mol % ESM exhibit extended circulation lifetimes compared with LNP mRNA systems containing 10 mol % DSPC, resulting in improved accumulation in extrahepatic tissues. Systems containing 40 mol % ESM result in significantly improved gene expression in spleen and bone marrow as well as liver post i.v. injection compared with 10 mol % DSPC LNP mRNAs. We conclude that LNP mRNAs containing high levels of helper lipid provide a new approach for transfecting hepatic and extrahepatic tissues.
Topics & Concepts
SphingomyelinMessenger RNAProtein expressionChemistryCell biologyInternal medicineEndocrinologyBiologyBiochemistryCholesterolGeneMedicineRNA Interference and Gene DeliveryLipid Membrane Structure and BehaviorRNA Research and Splicing