Lipid nanoparticle-mediated CRISPR/Cas9 delivery enables efficient trabecular meshwork gene editing in mice

Dec 4, 2025Journal of controlled release : official journal of the Controlled Release Society

Using lipid nanoparticles to deliver CRISPR for efficient gene editing in the eye's fluid drainage system in mice

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Abstract

SM102-based lipid nanoparticles achieved the highest transfection efficiency for gene delivery to ocular tissues, particularly in the trabecular meshwork.

  • Transfection efficiency of SM102-GFP was superior among three tested formulations in cultured ocular cells.
  • After intravitreal injection in mice, GFP expression peaked in the trabecular meshwork one week later and could be re-induced with a second dose.
  • SM102-GFP demonstrated better specificity for the trabecular meshwork and reduced retinal inflammation compared to adeno-associated viral and adenoviral vectors.
  • Co-delivery of CRISPR components via SM102-based lipid nanoparticles enabled knockout of Matrix Gla Protein, influencing intraocular pressure and anterior chamber dynamics.
  • Mgp knockout resulted in elevated intraocular pressure and signs of retinal stress, consistent with features of primary open-angle glaucoma.

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