The therapy, dubbed RUNX1-Trap, reduced excess scar tissue and the formation of new scar tissue in cultured cells and animal models.
Surgery—and blindness—from proliferative vitreoretinopathy (PVR) following retinal detachment may soon become a thing of the past.
Researchers at Massachusetts Eye and Ear (United States) have engineered a novel mRNA therapy, dubbed RUNX1-Trap, that has shown success in preclinical studies with animal and cell models at preventing the formation of scar tissue and abnormal blood vessels in eyes with PVR—two significant contributors to vision loss from the condition.
The results of the study were published on November 27 in Science Translational Medicine.1
The novel therapeutic strategy involves using mRNA to directly target the molecular pathways involved in scar tissue formation. Their results indicate that this could provide a safer, non-surgical option to prevent PVR and possibly a variety of other sight-threatening retinal conditions.
“This therapy is the first to deliver mRNA-based treatments inside the eye,” said Dr. Leo A. Kim, an investigator in the study and Monte J. Wallace Ophthalmology Chair in Retina at Mass Eye and Ear.
The study included testing in disease-induced rabbit, mouse and human ex vivo explant models. And while the therapy is still in the early stages of research and hasn’t been tested on humans yet, these preliminary results offer promising insights into the future of retinal disease treatment.
The treatment, according to Dr. Kim, also showed off some unexpected properties.
“We were pleasantly surprised that we could even use this approach inside the eye without causing excessive inflammation. We hope that these early findings can usher in new treatment options for PVR and other eye diseases.”
In the meantime, expectations surrounding the potential impact of the experimental treatment remain high. PVR patients currently have limited options beyond high-risk surgeries, and this new mRNA therapy could represent a major breakthrough for managing fibrosis and avoiding the operating table—eliminating a major potential downside to retinal detachment surgery.
How RUNX1-Trap mRNA therapy works
In the study, researchers explored the use of mRNA as a therapeutic tool for eye diseases, focusing on proliferative vitreoretinopathy (PVR) and abnormal blood vessel growth. mRNA is a critical molecule that acts as a messenger in cells, carrying genetic instructions from DNA to ribosomes, where it directs the synthesis of proteins. By introducing synthetic mRNA into cells, researchers were able to lead them to produce specific proteins, even ones not naturally present in the cell’s genome.¹
In the case of PVR, the researchers developed mRNAs encoding proteins involved in scar tissue formation, aiming to regulate this process in the eye. One key target was RUNX1, a protein that controls the expression of genes responsible for turning eye cells into scar tissue. Using cell-based, tissue-based and preclinical models, the team demonstrated that mRNA-based therapeutics could be safely applied to treat eye conditions, offering promising potential for targeted treatments in retinal diseases.
To block RUNX1’s activity, the team developed an mRNA-based treatment called RUNX1-Trap. This therapy “traps” the protein in the cell’s cytoplasm, preventing it from entering the nucleus, where it would normally initiate the gene expression responsible for scar tissue and abnormal blood vessel formation. Remarkably, in preclinical models, this approach successfully halted both processes.
Looking ahead: Expanding mRNA’s reach in ophthalmology
The study’s implications extend far beyond PVR. The research team aims to utilize the RUNX1-Trap therapy to address other retinal disorders where abnormal blood vessel growth and scar tissue formation play significant roles in vision loss.
However, as with any new therapeutic approach, there are challenges ahead. One key issue is the relatively short lifespan of mRNA inside the cell, which means that multiple doses may be required to maintain therapeutic effects. Researchers are now working to extend the duration of mRNA activity in the eye, as well as to identify the best timing for treatment to optimize outcomes.
“This work is the result of substantial effort put forth by our team, encompassing multiple experts across several different fields. It demonstrates novel applications of mRNA technology in ophthalmology and has implications for other aspects of medicine as well,” said Dr. William Miller, a co-first author of the study.
Dr. Miller wasn’t the only scientist in the research that noticed its transformative potential in applications beyond PVA.
“We believe targeting RUNX1 could lead to new therapies for sight-threatening conditions,” Dr. Arboleda-Velasquez, associate scientist at Mass Eye and Ear, said.
“The same idea of making dominant negative molecules produced using mRNA could result in the generation of potentially effective treatments for other conditions, greatly expanding the potential uses for mRNA.”
As the research progresses, the team plans to refine the treatment and test it further in animal models and, eventually, in human clinical trials. For now, the findings represent a promising proof of concept, offering a glimpse into a future where mRNA technology could dramatically improve outcomes for patients with eye diseases and beyond.
With continued investment and innovation, we may soon see mRNA-based therapies become a mainstay in the fight against blindness, reshaping the landscape of ophthalmology and advancing our understanding of how to treat complex, vision-threatening conditions.
Reference
- O’Hare M, Miller WP, Arevalo-Alquichire S, et al. An mRNA-encoded dominant-negative inhibitor of transcription factor RUNX1 suppresses vitreoretinal disease in experimental models. Sci Transl Med. 2024;16(775):eadh0994.
