Doctors have for the first time administered a drug designed to edit DNA directly inside a human body using "prime editing," a more precise and safer version of the well-known CRISPR system. The first patient was a person with Wilson's disease, an inherited disorder of copper metabolism that, left untreated, destroys the liver and the brain. The clinical trial is being conducted by the biotechnology company Prime Medicine, based in Cambridge, Massachusetts.
CRISPR technology makes it possible to alter genes. Its first version, CRISPR-Cas9, cuts both strands of DNA in order to switch off a defective gene. It is an effective but rather crude tool: sometimes, when the cut DNA is "repaired," the cell makes errors that can lead to the loss of entire segments of a chromosome. In 2024, the first therapy based on this method was approved, for the treatment of inherited blood diseases.
To avoid damaging the genome, scientists have developed gentler methods. First came "base editing," which replaces individual "letters" of the genetic code without breaking the DNA double helix. In 2019, "prime editing" was introduced. It nicks only one strand of DNA and uses a special guide molecule that carries a template for the required correction. This system can not only change individual DNA "letters" but also insert or delete short fragments of the genetic code. According to its creators, it is capable of correcting up to 89% of known disease-causing mutations.
The new technology has already proven its effectiveness in the laboratory. Previously, researchers from Prime Medicine used it to correct a defect in blood stem cells taken from patients with a rare immune disease. However, this approach requires individual work with each person's cells outside the body, which is very expensive.
In the current trial, the drug, called PM577a, is administered into the bloodstream. It is encased in fat nanoparticles, which deliver it to liver cells. There, it is supposed to correct a mutation in the gene responsible for removing copper from the body. According to the company's estimates, repairing 20 to 30% of liver cells is enough for a therapeutic effect. In experiments on monkeys, a single injection corrected about half of the liver cells without causing any noticeable side effects.
The first results of human trials, which will show the safety and effectiveness of the method, are expected next year. If they are successful, prime editing could become the basis for treating other genetic diseases as well.
We created prime editing five and a half years ago as a universal and precise technology that in principle could correct nearly all mutations known to cause genetic diseases. Today's data is a milestone in medicine.
— David Liu, co-founder of Prime Medicine
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