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mRNA Therapeutics for Corneal Endothelium Regeneration

A novel mRNA-based therapy that induces corneal endothelium regeneration to restore vision loss

Problem:

Corneal endothelial cells are critical for maintaining a clear cornea, mainly by pumping fluid out of the tissue. Decrease in number of these cells results in the clouding of the cornea that leads to vision loss. The standard of care for Fuchs Endothelial Corneal Dystrophy (FECD) is corneal transplantation. However, in addition to the procedure being invasive and costly, there is an immense shortage of cornea donors (approximately 1 cornea available for 70 needed).

Solution:

Induce proliferation of corneal endothelial cells to reverse loss of cells using mRNA therapeutics delivered directly into the eye.

Technology:

Cells of the corneal endothelium do not proliferate to replenish their number, which causes a decline in cell density with age. Confounding genetic factors or injury lead to further decline that results in the clouding of the cornea and loss of vision. The inventor created a combination of mRNA therapeutics that include Cdk4, Ccnd1, Myc, Sox2, and Yap. When these mRNAs were delivered directly into the eyes of aged mice, they effectively led to corneal endothelium regeneration by inducing a transient wave of cell proliferation.

Advantages:

No major surgery required – less complications.
No cornea donor required.
Cost and safety profile of mRNA therapeutics.
Easy to modulate mRNA dosage.

A) Experimental design for induced proliferation of corneal endothelial cells in vivo, via direct eye injection of mRNAs therapeutics. Cells that incorporate the mRNAs are traced by real-time live imaging to analyze efficacy. B) Quantification of change in the number of labeled cells that receive the mRNA therapeutics (CCMSY) versus Control. [N = 7 corneas, P < 0.0001; two-way ANOVA]. C) Graph showing the change in cell density in the corneal endothelium after injection with the mRNA therapeutics. The standard curve represents the normal decline in endothelial cell density with age. Note that the mRNA therapeutics reverse the effective age phenotype of one-year-old mouse to that of a three-month-old.