Using a new experimental technique to fix faulty eye cells, a United States team has been able to repair a gene mutation that causes Leber congenital amaurosis (LCA), one form of childhood blindness.
The scientists showed that their approach worked in lab-grown cells derived from a patient with LCA, a currently untreatable inherited disease, and a mouse model that mimics the disease.
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.
“Our goal is to design a package that will carry CRISPR base editors to the retina,” said Associate Professor Bikash Pattnaik, from the University of Wisconsin-Madison (UW-Madison), who led the study, published in the Journal of Clinical Investigation.1
“It will be able to introduce nanoparticles in the eye, and those nanoparticles will be designed to target the cell types identified for therapy.”
…the research team… expects the nanoparticle-packaged CRISPR technology will be able to treat other inherited eye diseases
Extended Applications
The researchers are seeking to develop treatments for LCA and Best disease, two forms of childhood blindness caused by retinal gene mutations.
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 colour perception.
While these diseases are relatively rare, the research team, which included scientists and engineers from UW–Madison, Harvard, and Massachusetts Institute of Technology, expects the nanoparticle-packaged CRISPR technology will be able to treat other inherited eye diseases.
An innovative technique distinguishes the work from a more typical method used in gene editing. The team said their method lowers the risk of problematic and unpredictable immune system responses. Another advantage of the technique is its specificity.
“Typically, drug development can take more than 30 years,” Assoc Prof Pattnaik said. “But with a multidisciplinary approach that brings together people with different expertise, we can cut this timeline significantly.”
Reference
- Kabra, M., Shahi, P.K., Pattnaik, B.R., et al., Nonviral base editing of KCNJ13 mutation preserves vision in a model of inherited retinal channelopathy. J Clin Invest. 2023 Oct 2;133(19):e171356. doi: 1172/JCI171356. PMID: 37561581; PMCID: PMC10541187.
