Fig. 1: Schematic illustration of hLSS mRNA-loaded pB-UC18 LNPs as an anti-cataract agent.

Three types of lipids, including pB-UC18 (ionizable lipids), DOPE (helper lipids), and DMG-PEG2k (PEGylated lipids), dissolved in ethanol self-assemble into aromatized LNPs in the presence of aqueous mRNA payloads via electrostatic interactions. Exogenous hLSS mRNA delivered by aromatized LNPs can be transported across cell membranes through multiple endocytic pathways and translated into hLSS proteins. mRNA-encoded hLSS proteins facilitate cyclization of (S)−2,3-oxidosqualene to lanosterol, thereby diminishing crystallin aggregation in rat cataract models. pB-UC18, (9Z,9’Z)-N,N’-(1,4-phenylenebis(methylene))bis(octadec-9-en-1-amine). DOPE, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine. DMG-PEG2k, 1,2-dimyristoyl-rac-glycero-3-methoxypolyethylene glycol-2000.