| 초록 |
Lipidnanoparticles (LNPs) are one of the efficient methods for delivering RNAtherapeutics to hepatocyte. Gene regulation potency of RNA therapeutics arehighly dependent on LNP formulations. Generally, various formulations of LNPshave been focused on targeting primary hepatocytes. However, LNPs mediatedliver cell type specific delivery for RNA therapeutics has not been studiedwell. In this study, we prepared amine-epoxide based ionizable lipids. Usingnewly synthesized ionizable lipid, we prepared mRNA encapsulated LNPs. A singleintravenous injection into LSL-tdTomato miceinduced >80% transfection efficiency of hepatocytes. Also, we were able todeliver RNA therapeutics to the liver sinusoidal endothelial cells (LSECs) byaddition of specific ligand to LNPs when higher PEG-lipid content was enough toprevent ApoEadsorption. This strategy may enable liver cell type specific delivery of RNAtherapeutics in clinical setting. |
