Development of Gene Editing as a Permanent Cure for Wet Age-related Macular Degeneration

Project Summary

The purpose of our study is to test a new gene-editing technology called "CRISPR" to treat wet age-related macular degeneration (AMD). Unlike current wet AMD treatments, which require frequent eye injections that are invasive, costly, and a burden to patients, gene editing allows us to manipulate the genome and suppress the abnormal blood vessels that causes blindness in wet AMD. We will first design a virus that can safely and effectively deliver the CRISPR gene editing enzymes into the eye to inactivate the growth factor that leads to abnormal vessel growth in mice. Next, we will test the effectiveness of this approach in monkeys by injecting the virus into their eyes, then performing laser injury to simulate abnormal vessel growth similar to wet AMD in humans, to see if CRISPR-based gene editing can suppress these abnormal vessels and permanently eliminate the need for eye injections. Finally, we will also carefully study the safety of gene editing by evaluating the risk of collateral damage from off-target mutations, as well as potential host immune responses which can inactivate the gene editing system. Together, our studies demonstrate a true “bench to benchside” adaptation of CRISPR-based gene editing from experiments in a test tube, to animal testing in mice, and to pre-clinical testing in primates. Importantly, the ability to permanently suppress these abnormal vessel growth factors will provide not just a treatment, but a true cure for wet AMD and similar retinal conditions that require eye injections. Once complete, our studies will provide a better understanding of using gene editing technology to eliminate need for eye injections, and a framework for human testing and clinical trials for curing wet AMD.