A multidisciplinary team of researchers from UW–Madison recently received a grant from the National Institutes of Health to develop and test a nonviral gene editing drug therapy to treat two hereditary eye diseases. Bikash Pattnaik, PhD, associate professor, Division of Neonatology and Newborn Nursery, is a co-investigator on the project “The CRISPR Vision Program: Nonviral Genome Editing Platforms to Treat Inherited Retinal Channelopathies.” The grant is expected to total $29 million over five years.
The study team will focus on developing treatments for two eye diseases that affect children. Best Disease (BD) is an inherited retinal disease that causes macular degeneration and loss of central vision, visual acuity, and color perception. The onset of Best disease varies, but it is usually diagnosed during childhood or adolescence. Leber Congenital Amaurosis (LCA) is another retinal eye disease that begins in infancy. It causes extreme farsightedness, sensitivity to light, and involuntary eye movements.
Pattnaik has studied the proteins that cause BD and LCA since the early 2000s. Since joining the Department of Pediatrics in 2008, his research has turned to learning how these proteins lead to disease and how to mitigate it. His work helped identify the genes that cause BD and LCA.
Gene editing technology, like CRISPR, is a recent scientific tool that can eliminate or replace mutated DNA sequencing one cell at a time. It holds great promise in the medical field, but its use has not been widespread as scientists look for ways to change the many cells that must be edited to make therapeutic improvements. The work that will take place through the CRISPR Vision Program will help close this gap, creating a means to edit genes on a mass scale.
“Our goal is to design a package that will carry CRISPR to the retina,” Pattnaik explained. “It will be able to squirt nanoparticles in the eye, and those nanoparticles will be designed to target the cell types identified for therapy.”
The study team aims to reach an Investigational New Drug (IND) within five years. And while BD and LCA are rare diseases, the technology developed will be able to treat other eye diseases. The aims for the project are ambitious, but the NIH set a clear goal for teams in this highly competitive grant competition: Achieve drug development faster through collaboration.
“Typically, drug development can take 30 to 35 years,” Pattnaik said. “But with a multidisciplinary approach that brings together people with different expertise, we can cut this timeline in half.”
The NIH award is a U19 through the National Institute of Neurological Disorders and Stroke. Krishanu Saha, PhD, associate professor of biomedical engineering, is the overall program leader. Pattnaik is a co-investigator of the Human Cell Assay Core along with David Gamm, MD, PhD, professor of ophthalmology and director of the McPherson Eye Research Institution; Project 2, “Develop an engineered Cas effector for in vivo cell-targeted delivery in the eye to treat autosomal dominant BEST disease,” also with Gamm; and Project 3, “Streamlined development of an IND with the silica nanocapsule loaded with Cas9 genome editors to disrupt the dominant BEST1 mutant allele,” with Saha. Pattnaik is the co-lead of Project 1, “Silica Nanocapsule-Mediated Nonviral Delivery of CRISPR Base Editor mRNA and Allele Specific sgRNA for Gene Correction in Leber Congenital Amaurosis,” with Shaoquin Gong, PhD, professor of ophthalmology and biomedical engineering.
You can read more about this research in the article “UW researchers will develop gene editing therapy to treat blindness,” published on June 6, 2023, by University Communications.