Fig. 2: LNP optimization and structure-activity relationship (SAR) study of cationic lipids for mRNA delivery.
From: Reformulating lipid nanoparticles for organ-targeted mRNA accumulation and translation
a Orthogonal screening of LNP formulations with four levels. b LNP formulation table for mRNA delivery validation in vivo. c Firefly luciferase (Fluc) mRNA translation by different LNP formulations (0.25 mg kg−1 mRNA). H heart, Lu lung, Li liver, K kidney, S spleen. d 6Ac1-C12 LNPs delivered mCherry mRNA at different mRNA doses. Scale bar: 200 μm. e In vitro screening of nAcx-Cm lipids by Fluc mRNA delivery to IGROV1 cells, recorded by relative light units (RLU) (25 ng mRNA, n = 3 biologically independent samples). f The heat map of luciferase expression upon transfecting IGROV1 cells with nAcx-Cm LNPs. g Relative hit rate of nAcx-Cm lipids with different branch numbers. h Relative hit rate of nAcx-Cm lipids with a single or double hydrophobic tails per branches. i Regarding nAcx-Cm lipids with the single tail per branch, 4-6 branched lipids exhibited high relative hit rate.
