Until now, genetic medicine faced a logistical barrier: there are over 8,000 known genetic diseases affecting hundreds of millions of people, but developing a specific drug for each of the over 200,000 possible mutations is nearly impossible. However, a new study published in the journal Nature could change the game.
A team led by the laboratory of David R. Liu has developed a strategy called PERT (Prime Editing-mediated Readthrough of premature Termination codons), an "agnostic" technique that does not need to be custom-designed for each disease but serves to treat a vast variety of them with a single chemical composition.
The problem: a premature "Stop" signal
To understand this breakthrough, one must visualize DNA as a set of instructions for making proteins. Approximately 24% of genetic diseases are due to what scientists call "nonsense mutations".
Imagine reading a sentence and suddenly encountering a period in the middle of it... The sentence loses its meaning. That is exactly what happens in these diseases: a mutation introduces a premature "stop signal" (premature termination codon). The cell's machinery stops reading the instructions halfway, and the resulting protein remains incomplete and nonfunctional.
The solution: change the driver, not the road
Most current gene therapies attempt to erase that erroneous period in the patient's DNA. The issue is that a specific "eraser" must be designed for each patient. The PERT strategy is different. Instead of fixing the broken gene (the road), scientists have modified the vehicle that reads the instructions: transfer RNA (tRNA).
tRNAs are responsible for transporting the building blocks (amino acids) to construct proteins. Liu's team used the Prime Editing technique to permanently modify one of the cell's tRNAs, turning it into a "suppressor tRNA".
This modified tRNA acts as an expert driver that, upon seeing the erroneous stop signal, ignores it, places the missing building block, and allows the protein construction to continue to completion. The revolutionary aspect is that a single type of editing can work for any disease caused by that type of stop signal, regardless of the affected gene.
Promising results in mice and human cells
The researchers tested this technique on human cells with mutations responsible for severe diseases like Batten disease, Tay-Sachs disease, and cystic fibrosis. In all cases, the treatment successfully restored the production of complete and functional proteins.
The most significant step was taken in animal trials. They used mice with Hurler syndrome, a disease that prevents the breakdown of certain sugars, causing severe damage to organs and the brain. After a single injection of the PERT therapy, the mice regained enzymatic activity, and most remarkably, they were cured of the pathology: the harmful accumulation of substances in the liver, heart, and brain almost completely disappeared.
Is it safe to ignore stop signals?
One of the major concerns was whether these "rebellious drivers" (suppressor tRNAs) would also skip real stop signals marking the natural end of proteins, which could be toxic.
The study demonstrates that the technique is surprisingly safe. Natural stop signals have a different "context" that protects them, so the treatment did not affect the normal termination of healthy proteins or alter the overall cell function. Additionally, by editing a cell's own gene instead of injecting foreign copies, long-term toxicity issues are avoided.
A future with fewer drugs, but more cures
This breakthrough opens the door to treating entire groups of patients with a single drug. As the authors explain, diseases like Duchenne muscular dystrophy, cystic fibrosis, or phenylketonuria could benefit from the same genetic "master key".
"The breadth of the global crisis of genetic diseases demands new approaches," write the researchers. With PERT, science takes a giant step towards a medicine that is not only precise but also scalable to reach millions of people.