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Scientists Explore New Molecular Tool to Treat Retinal Degenerative Diseases

Scientists Explore New Molecular Tool to Treat Retinal Degenerative Diseases

December 18, 2023

Millions in the U.S. grappling with reduced eyesight due to retinal degenerative diseases may soon find hope. Researchers at the University at Albany's RNA Institute, collaborating with the University of Buffalo's Jacobs School of Medicine, secured a $1.8 million grant from the National Eye Institute. The four-year study focuses on a novel molecular tool for treating retinal degenerative diseases.

At the core of the project is the "hammerhead ribozyme," an engineered RNA molecule designed to catalyze a precise chemical reaction, cutting a messenger RNA (mRNA) strand at a specific location. By targeting the genetic code contributing to vision impairment, this innovative approach could potentially slow down or halt the progression of various sight-affecting diseases, preserving retinal function and mitigating vision loss.

Co-investigator Ken Halvorsen, a senior research scientist at the RNA Institute, said: "What makes this particular hammerhead ribozyme special is its speed. It is unusually adept at binding and cutting target mRNA sequences quickly, compared to other ribozymes embedded in restrictive scaffolds, which are used for similar applications yet operate at a slower rate.”

"My lab will use a combination of biophysical approaches to determine the thermodynamics, kinetics and mechanistic changes involved in ribozyme binding, substrate cleavage and ribozyme release — to help us understand how this type of hammerhead ribozyme is able to operate so quickly. Our ultimate goal is to improve the efficiency of the ribozyme as it moves along the path toward clinical use.”

The study also seeks to establish rules for designing improved ribozymes. By manipulating RNA in retinal cells, the team hopes to apply these rules to treat various diseases affecting different body systems.

Co-investigator Jia Sheng, an associate professor at the RNA Institute, emphasizes the project's goal to provide new therapeutics for retinal degenerations, including autosomal dominant retinitis pigmentosa. Using expertise in RNA chemical biology, the team plans to design and synthesize new hammerhead ribozymes to block pathogenic mRNA expressions.

Research Scientist Sweta Vangaveti, another co-investigator, will employ molecular modeling and simulations to illustrate atomic-level structural changes between hammerhead ribozymes and target genetic sequences. The study, a collaboration between science and real-world health outcomes, holds great promise for advancing biomedical applications.

“This is one of the most ‘translational’ projects our lab has ever worked on, so I’m excited about the possibility that our work in understanding the activity of the hammerhead ribozyme could directly lead to improvements in a therapeutic that may be brought to clinical use,” said Halvorsen. “It’s also interesting to work with Dr. Jack Sullivan at Buffalo, a practicing ophthalmologist, because the science and technology we are working on will directly connect with real-world health outcomes."