Using mRNA to deliver gene editing that reverses eye pressure in myocilin glaucoma by targeting fluid drainage tissue

Mutations in the myocilin gene are the leading genetic cause of primary open angle glaucoma.

• Mutations in the myocilin gene lead to a toxic gain-of-function phenotype associated with the accumulation of misfolded MYOC protein.
• This accumulation causes endoplasmic reticulum stress and contributes to the death of trabecular meshwork cells.
• The resulting cell death is linked to an elevation of intraocular pressure.
• Delivery of Cas9 mRNA via a cationic lipid polymer effectively targets the trabecular meshwork and edits the myocilin gene.
• In a mouse model, this approach reduced the intracellular accumulation of mutant MYOC and alleviated endoplasmic reticulum stress.

Simplified