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Using a new experimental technique to fix faulty eye cells, a team led by University of Wisconsin researchers was able to repair a gene mutation that causes one form of childhood blindness.
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October 5, 2023
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<a href="/about/news-and-events/news?topic=401" hreflang="en">Gene Therapy</a>
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<a href="/about/news-and-events/news?topic=55" hreflang="en">Leber Congenital Amaurosis</a>
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<a href="/about/news-and-events/news?topic=56" hreflang="en">Rare Diseases</a>
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<p>Using a new experimental technique to fix faulty eye cells, a team led by University of Wisconsin researchers was able to repair a gene mutation that causes one form of childhood blindness. The scientists showed that their approach worked in lab-grown cells derived from a patient with the currently untreatable inherited disease Leber congenital amaurosis (LCA) and a mouse model that mimics the disease.</p>
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<p>The method hinges on delivering gene-editing tool CRISPR base editor to retinal cells using silica nanocapsules. The proof-of-concept study restored the function of a protein that controls the flow of potassium ions in retinal tissue, which allows light-detecting cells to work properly.</p>
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<p>“Our goal is to design a package that will carry CRISPR base editors to the retina,” said Bikash Pattnaik, co-investigator and associate professor of pediatrics at the UW School of Medicine and Public Health. “It will be able to introduce nanoparticles in the eye, and those nanoparticles will be designed to target the cell types identified for therapy.”</p>
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<p>Pattnaik, affiliated with the Department of Ophthalmology and Visual Sciences, led a team including scientists and engineers from UW–Madison, Harvard, and MIT that published the study in the Journal of Clinical Investigation. The researchers are seeking to develop treatments for two forms of childhood blindness caused by retinal gene mutations, LCA and Best disease, which is also known as Best vitelliform macular dystrophy. LCA begins in infancy and causes extreme farsightedness, sensitivity to light, and involuntary eye movements. Best disease, usually diagnosed in childhood, causes macular degeneration and loss of central vision, visual acuity, and color perception.</p>
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<p>The team reasoned that silica nanocapsules do not interact with the body, lowering the risk of problematic and unpredictable immune system responses that viral methods may elicit. Another advantage of the technique is its specificity. “The rapid pace of genetic diagnosis development has enabled accuracy in identifying disease-causing mutations, and we used base editing to correct a specific error in the DNA sequence of patients, overcoming several challenges through the collaborative team science approach,” said research associate Meha Kabra.</p>
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