Yan Zhang, Ph.D., Shahzad Mian, M.D., Lev Prasov, M.D., Ph.D.
Editing Genes to Treat Corneal Dystrophies
initiative at the U-M Medical School Office of Research, was the perfect opportunity to develop this project. The program empowers a team of U-M researchers (‘scouts’) to identify bold early-stage ideas and spark the needed connections across the medical campus to Gene editing therapy—making changes to the DNA of make them happen. cells to correct mutations—is a promising avenue to The idea caught the attention of ‘scout’ Ivo Dinov, treat inherited ocular defects and blinding disorders. Ph.D., who introduced Drs. Prasov and Mian to Yan Much research is devoted to applying gene editing Zhang, Ph.D., a researcher in the Department of Biologito conditions of the retina. Yet, as ophthalmic genetical Chemistry. Dr. Zhang is an expert in developing and cist Lev Prasov, M.D., Ph.D., and cornea specialist applying CRISPR-based technologies to tackle diverse Shahzad Mian, M.D., note, far less attention has been biological challenges. paid to how gene editing might be With funding from a Research used to treat corneal dystrophies, Scouts grant, their collaboration IT’S A TESTAMENT TO WHAT’S which impact about one in 2,000 will focus on two types of genetiPOSSIBLE IN AN INSTITUTION Americans. cally linked corneal dystrophies THAT FOSTERS COLLABORATION “Corneal dystrophies are good both linked to disruption of the AND PRIORITIZES BOLD SCIENCE. therapeutic candidates for gene same protein (TGFBI): lattice and editing,” says Dr. Prasov. “Specific granular. — Shahzad Mian, M.D. genetic mutations common to Mining data from electronic several dystrophies have already been identified. Moremedical records, Drs. Prasov and Mian will identify over, those genes have been shown to be amenable to Kellogg patients with those corneal dystrophies for manipulation with editing tools like CRISPR-Cas9 base genetic testing. Separately, they will use donor corneal editing.” tissue to test different methods of delivering a treatDr. Mian sees two promising paths for using gene ment into the cornea to modify the gene. Dr. Zhang will editing to treat inherited corneal dystrophies. The apply the latest CRISPR technology to design various first is early intervention. “This could prove a sightgene editing reagents, evaluating them first in corneal saving approach for a patient identified as carrying cell lines, then in corneal tissue samples to identify the a mutation whose disease has not yet progressed to reagent that produces the optimal editing change. a completely opaque cornea.” They hope the project will generate enough data The second is treating dystrophies that recur in to apply for larger NIH and/or foundation funding. “We corneal grafts. “Recurrence is all too common in corneal could not have pursued this idea without Dr. Zhang, and transplants,” Dr. Mian says. “If we could ‘edit out’ the we would likely never have connected with her had it genetic culprit, it would save many patients from neednot been for the Scout program,” says Dr. Mian. “It’s ing multiple transplants.” a testament to what’s possible in an institution that The Research Scouts Program, a new funding fosters collaboration and prioritizes bold science.”
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