Lipid nanoparticle-mediated intracameral mRNA delivery facilitates gene expression and editing in the anterior chamber of the eye

Jan 28, 2025Journal of controlled release : official journal of the Controlled Release Society

Gene delivery and editing in the front part of the eye using lipid nanoparticles carrying mRNA

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Abstract

IC injections of lipid nanoparticles (LNPs) resulted in robust protein expression and gene editing in the trabecular meshwork.

  • LNP-mediated delivery of Cre-mRNA led to significant tdTomato expression in the angle and corneal endothelium of Ai9 mice.
  • Localized protein expression from mCherry-mRNA LNPs in C57BL/6 mice peaked at 72 hours and declined over 120 hours.
  • LNPs encapsulating Cas9 mRNA with sgAi9 achieved up to 14.3% editing efficiency for in vivo gene editing in Ai9 mice.
  • tdTomato expression was induced in the iridocorneal angle, demonstrating the potential for LNPs in gene editing applications.
  • No ocular toxicity was observed with the intracameral administration of LNPs, suggesting safety for this delivery method.

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