Eyeworld

I SEPTEMBER 2020 | EYEWORLD | 35 by Ellen Stodola Editorial Co-Director to deliver the material, as well as assessing the safety and toxicity of these treatments." Dr. Jun added that so far, results in animal testing have been promising. Personalized allele-specific CRISPR gene editing to treat autosomal dominant disorders Dr. Jun is working actively on CRISPR treat- ments for corneal dystrophies. He noted that the two dystrophies he's "most excited" about applying it to are Fuchs dystrophy and TGFBI disorders. Fuchs dystrophy is a common disorder and the leading cause of corneal transplants world- wide, Dr. Jun said. There are a lot of patients who have issues and have lost vision but haven't gotten to the point of needing a transplant, he said, adding that in some parts of the world, there is also limited access to transplant tissue. T here have been a number of recent advances in the field of gene editing. Two experts discussed this progress, highlighting the development of clus- tered regularly interspaced short palin- dromic repeats (CRISPR)/CRISPR- associated protein 9 (Cas9) systems. Tara Moore, PhD, said that CRISPR/Cas9 is finally progressing into clinical trials, with pre- liminary results showing evidence of the tech- nique being safe and feasible to treat diseases. 1 She added that there is currently a clini- cal trial in recruitment stage, sponsored and organized by Allergan and Editas, that evaluates safety and efficacy of CRISPR treatment for Leber congenital amaurosis 10, an eye disorder affecting the retina. It is only one of few clinical trials that is being done in vivo, she said. This treatment was the first one to edit human genes within the body, with the first pa- tients being treated at Oregon Health & Science University. Due to a number of unique features of the eye, Dr. Moore said that there are several factors that could help genetic treatments for genetic eye disease to be successful. For cor- neal disease, some of these factors include the exterior element—the location of the eye and cornea—the small size and area to be treated, the ease of viewing pathology and assessing disease regression without invasive technologies, the thinking that there is some immune privi- lege, and no need for IV treatment or exposure to other organs. More in vivo trials will follow, she added. Using CRISPR/Cas9 simplifies the basic ways of altering genes and cells, said Albert Jun, MD, PhD. "The process used to be much more involved and to generate even a single method to change genes was much more cumbersome," he said. The CRISPR approach simplifies gene ther- apy design, he said, adding that "it's theoretically easy to create a genetic treatment for a mutation that's relatively uncommon." "There's so much excitement because you dial in the treatment," Dr. Jun said. "The practicalities will come into play when trying Exploring corneal genetics and gene editing continued on page 36 At a glance • With options for CRISPR gene editing in the works, experts are excited about its potential application to Fuchs dystrophy, TGFBI disorders, retinitis pigmentosa, inherited retinal dystrophies, and Huntington's disease and hemophilia disor- ders. • In order to get this treatment onto the tissue or into a cell, chemicals or a virus may be used. • CRISPR's allele specificity can be exploited in therapeutic treatments where only the dis- ease-causing allele is targeted and disrupted and healthy allele remains and minimizes adverse effects.

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