biostudies-literatureUnknown16(1)Song RCataract caused by crystallin aggregation is the leading cause of vision impairment and blindness globally. The only available treatment option so far is surgery. In this study, we leverage lipid nanoparticles (LNPs)-formulated mRNA encoding human lanosterol synthase (hLSS) to elevate lanosterol levels in the lens as a potential anti-cataract therapy. hLSS mRNA delivered with aromatized LNPs can be avidly taken up and translated into hLSS proteins in mammalian cells. mRNA formulations administered via intravitreal, subconjunctival, intracameral, or subretinal injection in rats display distinct kinetics and bio-distribution profiles, among which intracameral injection achieves sustained and selective protein expression in the lens. In comparison to clinically used LNPs, aromatized LNPs showNature communications8522https://www.ebi.ac.uk/biostudies/studies/S-EPMC12474983biostudies-literatureOcular delivery of lipid nanoparticles-formulated mRNA encoding lanosterol synthase ameliorates cataract in rats.PMC12474983Liu ZSong RLin YZhang MLi BZhang RZhao JfalseOcular delivery of lipid nanoparticles-formulated mRNA encoding lanosterol synthase ameliorates cataract in rats.Cataract caused by crystallin aggregation is the leading cause of vision impairment and blindness globally. The only available treatment option so far is surgery. In this study, we leverage lipid nanoparticles (LNPs)-formulated mRNA encoding human lanosterol synthase (hLSS) to elevate lanosterol levels in the lens as a potential anti-cataract therapy. hLSS mRNA delivered with aromatized LNPs can be avidly taken up and translated into hLSS proteins in mammalian cells. mRNA formulations administered via intravitreal, subconjunctival, intracameral, or subretinal injection in rats display distinct kinetics and bio-distribution profiles, among which intracameral injection achieves sustained and selective protein expression in the lens. In comparison to clinically used LNPs, aromatized LNPs show2025-01-01T00:00:00Z2025 Sep2026-06-03T22:49:01.362Z2026-05-02T03:11:47.112ZS-EPMC124749834100630110.1038/s41467-025-63553-5