Researchers Correct Genetic Defect Associated with Retinitis Pigmentosa Using Modified RNA Molecules

18. 06. 2026

A research team from the Institute of Molecular Genetics of the Czech Academy of Sciences, led by David Staněk, has developed an experimental RNA-based approach that corrects a genetic defect linked to retinitis pigmentosa, an inherited eye disease that progressively impairs vision. Published in Molecular Therapy, the study shows that specially designed antisense oligonucleotides can repair faulty RNA processing and restore production of a key protein in patient-derived retinal cells. The findings provide proof of principle for a mutation-targeted strategy and may open new possibilities for the future development of personalized therapies for inherited retinal diseases.

Disease that slowly takes away sight

Retinitis pigmentosa is one of the most common inherited diseases of the retina. Patients typically first experience night blindness and difficulty seeing in low light. As the disease progresses, they gradually lose peripheral vision, often developing so-called tunnel vision, and in severe cases may become blind.
Although rare, the disease has a profound impact on patients’ independence, education, employment and everyday life. Despite major advances in genetics, treatment options remain limited and, for most forms of retinitis pigmentosa, there is still no therapy that directly addresses the underlying molecular cause.
This challenge motivated researchers from the Institute of Molecular Genetics to focus on one of the genes most frequently associated with the disease, PRPF31. By understanding exactly how mutations in this gene disrupt normal cellular processes, the team hoped to identify a way not only to explain the disease mechanism but also to correct it.

Looking for the cause

The research team at the Institute of Molecular Genetics focused on a gene called PRPF31, which is one of the most frequent causes of autosomal dominant retinitis pigmentosa. This gene carries instructions for producing a protein required for a process known as RNA splicing. Splicing is an essential step in gene expression: before a gene can be translated into a protein, the cell must correctly edit its RNA copy by removing unnecessary parts and joining the meaningful sections together.

“When splicing goes wrong, the cell may produce an incorrect message and, as a result, too little of the functional protein,” explains David Staněk, head of the Laboratory of RNA Biology at the Institute of Molecular Genetics of the Czech Academy of Sciences. “Retinal cells are particularly sensitive to defects in RNA processing but we still don't fully understand why.”

In the new study, researchers identified a previously unknown mutation in the PRPF31 gene in a family affected by retinitis pigmentosa. The mutation does not lie in the part of the gene that directly encodes the protein. Instead, it is located in an intronic region — a section that is normally removed during RNA splicing and thus should not affect protein production. However, the mutation creates a false signal for the cellular splicing machinery. As a result, the cells process RNA incorrectly and produce less functional PRPF31 protein.

Recreating the disease in the laboratory

To study the disease mechanism, the scientists generated induced pluripotent stem cells from patients. These are cells that can be created from a patient’s own blood cells and then guided in the laboratory to become other cell types. In this case, the team differentiated them into retinal pigment epithelium cells, which play a crucial supporting role in the retina and are affected in retinitis pigmentosa. This patient-derived model allowed the researchers to observe how the mutation disrupts RNA processing in retinal cells and to test whether the defect could be corrected.
Repairing the genetic message
The team then designed a panel of antisense oligonucleotides, short synthetic RNA molecules that bind to cellular RNA and can influence its processing. In simple terms, they can help the cell ignore the false signal created by the mutation and encourage production of the correct RNA message. One of the tested candidates successfully rescued splicing of PRPF31 RNA. Importantly, the treatment also increased the amount of PRPF31 protein in patient-derived retinal cells.
“What is exciting is that we were not only able to describe the mutation and understand its effect, but also to design a molecule that partially corrects the defect in patient-derived cells,” says David Staněk. “This is still experimental research, not a treatment ready for patients, but it shows that the molecular defect can be targeted very precisely.”
The findings expand current knowledge in two important ways. First, they characterized a new disease-causing mutation in non-coding genomic regions, which are often overlooked in genetic mapping. Second, they demonstrate that the defect can be corrected using a targeted therapy, restoring production of the missing protein in a cellular model of the disease.

New possibilities for RNA medicine

The study also contributes to the rapidly developing field of RNA therapeutics. Antisense oligonucleotides are already used to treat several genetic diseases, and the eye is considered a promising target for this type of therapy because RNA drugs can be delivered locally to retinal tissues.
According to the authors, further research will be needed to test whether the approach is safe and effective in more advanced preclinical models. The current study is therefore an important first step rather than a clinical treatment. However, it provides a foundation for the future development of personalized therapies for patients carrying this or similar splicing mutations.

Why basic research matters

“Basic research into RNA processing may seem far removed from clinical medicine, but this study shows how understanding a fundamental cellular mechanism can open the door to new therapeutic strategies,” says David Staněk. “If we want to treat genetic diseases effectively, we first need to understand exactly what goes wrong inside the cell.”
The work was carried out by researchers from the Institute of Molecular Genetics of the Czech Academy of Sciences in collaboration with clinical and scientific partners from Charles University, General University Hospital in Prague, Masaryk University, University Hospital Brno, and University of Colorado Boulder.
The research was supported by the project RNA for Therapy, co-funded by the European Union, the Czech Science Foundation, the Ministry of Health of the Czech Republic and other national research programmes.

Publication:
https://www.sciencedirect.com/science/article/pii/S1525001626004788?ref=cra_js_challenge&fr=RR-1

Contact:

Ester Jarour, B.Sc.
Institute of Molecular Genetics of the Czech Academy of Sciences
+420 774 798 184
ester.jarour@img.cas.cz

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Researchers Correct Genetic Defect Associated with Retinitis Pigmentosa Using Modified RNA Molecules

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