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

Abstract

Lipid nanoparticles (LNPs) have shown great potential in the field of gene therapy for retinal diseases. To expand on this application, we investigated LNP-mediated mRNA delivery to the anterior chamber of the eye via the intracameral (IC) route of administration. Here, we show that IC injections of LNPs facilitated protein expression and gene editing in the trabecular meshwork (TM). Administration of Cre-mRNA LNPs to Ai9 mice resulted in robust tdTomato expression in the angle and corneal endothelium. In C57BL/6 mice, mCherry-mRNA LNPs demonstrated localized protein expression in the TM, which peaked at 72 h and subsequently declined over 120 h. Additionally, LNPs encapsulating Cas9 mRNA with sgAi9 enabled in vivo gene editing in Ai9 mice, with up to 14.3 % editing efficiency. This induced tdTomato expression in the iridocorneal angle, validating the potential of LNPs for gene editing applications. Importantly, no ocular toxicity was observed, indicating the safety of the IC LNP administration. Our findings highlight the use of LNPs for targeted gene therapy and editing, paving the path for the treatment of diseases such as glaucoma in the anterior eye.

Keywords: Gene editing; Intracameral administration; Lipid nanoparticles; Ocular gene therapy; Trabecular meshwork; mRNA delivery.