Joint research team develops new treatment for congenital retinal disease

Researchers from three university hospitals have developed a technology to synthesize RNA protein suitable for treating congenital retinal diseases.

A joint research team has developed a new treatment method for congenital retinal disease. They are, from left, Professor Kim Jeong-hun at Seoul National University Hospital, Professor Bae Sang-su at Hanyang University, and Professor Woo Jae-sung at Korea University.

Congenital retinal disease, caused by a genetic mutation, is the leading cause of blindness in children inflicting about two million patients worldwide, according to the Seoul National University Hospital (SNUH).

As a treatment, CRISPR (clustered regularly interspaced short palindromic repeats), or gene editing, which removes or replaces genes in units of bases, has received attention as a solution to this disease. Notably, the base corrector method, which does not cut DNA and has fewer side effects, has received spotlight, the hospital added.

The joint research team -- led by Professor Kim Jeong-hun of the Department of Ophthalmology at SNUH -- secured a base corrector ribonucleic acid protein with a purity of 99 percent or more, meeting international standards from the fetal cell line HEK293E.

Professor Bae Sang-su at Hanyang University and Professor Woo Jae-sung at Korea University also participated in the trial.

Afterward, the team administered the protein into rd12 mice, a mouse model suffering from congenital retinal disease due to inability to produce normal RPE65 protein, confirming the excellent therapeutic effect.

The researchers administered the obtained base corrector ribonucleic acid protein to mice, they confirmed normal DNA correction and RPE65 protein expression, the hospital said. The base corrector protein synthesis technology was also superior in stability, speed, and cost compared to the widely used virus method. The method also has fewer side effects and faster efficacy.

In the protein method, the off-target effect, which is a side effect of gene expression at a site other than the original target, was significantly less than the base corrector's expression using a plasmid. The speed of the treatment was also excellent as the team achieved DNA editing and expression in a shorter time.

The hospital added that the method could lower the economic burden on patients.

The cost of ribonucleic acid protein synthesis is lower than that of viruses, so the treatment price is relatively low. As an example, the cost of one treatment for Luxturna, a virus-based treatment for congenital retinal disease, is about 500 million won ($427,642), while Eylea, a protein-based therapy for macular degeneration, costs about 2 million won per treatment.

A simple comparison is difficult. However, in general, protein-based therapeutics form a more reasonable price range than virus-based therapeutics.

The hospital expected that the new method would alleviate some of the concerns about gene-editing therapeutics.

“Safety is as important as effectiveness in the treatment of children with congenital retinal disease,” Professor Kim said. “The base corrector ribonucleic acid protein will be an innovative treatment strategy that can prevent blindness due to congenital retinal disease by safely correcting genetic mutations in desired areas.”

Professor Bae also said, “Since the base corrector does not cause DNA double helix breaks, it is a safer gene-editing method compared to the existing CRISPR gene scissors.”