ArticleNature communications2025
Ocular delivery of lipid nanoparticles-formulated mRNA encoding lanosterol synthase ameliorates cataract in rats.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- In situ bioactive nanocoating enables transocular delivery of permeable drug for dual-location intervention of ocular surface and fundus disorders.Bioactive materials · 2027Article
- Advancing Treatment of Degenerative Eye Diseases at the Nanoscale.Smart medicine · 2026Review
- Checkpoint inhibition and beyond: Precision immune engineering for the immune-privileged landscape of ocular malignancies.BioImpacts : BI · 2026Review
- Lens epithelial cells senescence in cataract pathogenesis and emerging therapeutic opportunities.Frontiers in cell and developmental biology · 2026Review
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7 authors.
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Abstract
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 show more than seven-fold higher mRNA delivery potency in rats upon intracameral injection, without inducing significant ocular lesions. Furthermore, ocular delivery of hLSS mRNA-loaded formulations leads to elevated levels of hLSS proteins and lanosterol within the lens and a remarkable improvement in cataract symptoms in two rat models of cataract. Collectively, topical delivery of hLSS mRNA-LNPs to the eyes offers a potential strategy to reduce intracellular aggregation of crystallins and ameliorate cataract development.
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