Lipid stereochemistry of lipid nanoparticles significantly influences mRNA expression levels in vivo

Introduction: Lipid nanoparticles (LNPs) are self-assembled by microfluidic mixing using four different lipids to encapsulate and deliver RNA into cells to treat diseases on the genetic level (1). Their RNA delivery potency depends on many factors, such as physicochemical properties and ionizable lipid choice. However, the influence of lipid stereochemistry on RNA delivery has rarely been studied (2). To investigate how stereoisomers alter the performance of LNP formulations, we selected three lipids with two isomers and investigated their influence on mRNA expression levels in vitro and in vivo.