Abstract

Lipid nanoparticles (LNP) have demonstrated high efficiency delivering RNA therapeutics in vivo. However, the properties of such nanoparticles obtained with conventional ionizable lipids are often hard to modulate,and especially their biodistribution profile. Such ionizable lipid-based nanoparticles often predominantly end up targeting the liver. One of the current challenges in the field consists of adjusting the particle chemical composition to the targeted application. Here, we have characterized a library of 10 innovative imidazolium-based cationic lipids as key component of cationic LNPs (cLNP). We disclose their chemical structures and demonstrate their efficacy generating LNPs through characterization of their hydrodynamic diameters, Zeta potentials and encapsulation efficiencies. The resulting particles display high transfection efficiencies and have little to no impact on cell viability in vitro, on HEK-293 and CaCo-2 cell lines. In vivo, the biodistribution of the cLNP highly depends on the cationic lipid chemical structures, targeting mainly lungs and spleen. Among this library, we have identified one cationic lipid as a potent additive in Moderna‘s Spikevax formulation.