Prime Medicine has dosed the first patient in a global trial of PM577a, an investigational therapy that delivers DNA-editing machinery directly into liver cells, marking the first known use of prime editing inside a living person.
A patient with Wilson disease received an intravenous infusion of PM577a in October 2026, becoming the first reported person to receive an in vivo prime-editing therapy. Prime Medicine, the company behind the treatment, expects initial clinical data from the trial in 2027.
Wilson disease is a rare inherited condition caused by mutations in the gene ATP7B, which disrupts the liver’s ability to clear excess copper. Left untreated, copper accumulates and damages the liver and nervous system; most patients currently manage the condition with lifelong copper-clearing medication.
What Prime Editing Is, and Why It Matters Here
Prime editing offers a more targeted approach to DNA correction than conventional gene-cutting tools, and that precision makes it a candidate for diseases where switching a gene off is not enough.
Standard CRISPR-Cas9 works largely by cutting DNA to disable a gene. Prime editing is designed to make more controlled sequence changes, rewriting specific DNA letters rather than simply breaking the strand.
That distinction matters for Wilson disease, where the goal is correcting a mutation rather than switching a gene off. Base editing, another precision approach, can change individual DNA letters but may not cover every correction required for particular ATP7B variants.
Casgevy is the only CRISPR therapy currently approved by the U.S. Food and Drug Administration, and it treats two inherited blood disorders by editing cells outside the body before reinfusing them. PM577a takes a different path: the editing components travel to the patient’s liver cells without any extraction step, a method known as in vivo editing.
Prime Medicine previously applied prime editing outside the body in a clinical trial for a rare immune disorder. The Wilson disease program is the company’s first clinical study to deliver the editing system directly into a patient.
How the Trial Works
PM577a is an investigational one-time infusion designed to correct the most common Wilson-disease-causing mutation in North America and Europe, with safety as the trial’s primary focus.
PM577a targets the H1069Q mutation in ATP7B, which Prime Medicine describes as the most prevalent Wilson-disease-causing variant in North America and Europe. Lipid nanoparticles carry the prime-editing components intravenously to hepatocytes, the liver cells that handle copper processing.
The open-label Phase 1/2 trial enrolls adults and adolescents across ascending dose groups, with safety and tolerability as its primary focus. The FDA cleared Prime Medicine’s investigational application; New Zealand’s Medsafe also authorized the program, enabling the global study. FDA clearance of an investigational application is not the same as product approval.
The Questions That 2027 Data Must Answer
No efficacy or safety results are available yet, and the first dosing confirms only that the therapy can be administered.
No copper-level, liver-function, or long-term safety results had been publicly reported as of the announcement. The first patient being dosed confirms the therapy can be administered; it does not establish that it works.
Delivery remains a central challenge for in vivo approaches, according to biomedical engineer Krishanu Saha, who has noted that the risks depend on what types of risks researchers and patients are willing to accept. Lipid nanoparticles must reach enough liver cells to produce a clinically meaningful effect while limiting exposure to unintended tissues.
Because the editing happens inside the body, researchers cannot inspect individual cells before treatment the way they can with laboratory-modified cells. Whether unintended edits or immune reactions emerge will be among the most closely watched signals in the trial.
A Field Moving Fast
Prime Medicine is part of a broader push to deliver precision DNA medicines directly into patients, with several other companies running parallel in vivo programs.
Prime Medicine is not alone in advancing this approach. Tessera Therapeutics is running an in vivo trial for alpha-1 antitrypsin deficiency using a related editing approach, and other programs in development include a base-editing therapy for a disorder associated with extremely high cholesterol and an in vivo CRISPR-Cas9 therapy for hereditary angioedema.
For Wilson disease patients who take copper-clearing drugs every day, the 2027 data may provide the first clinical evidence of whether PM577a can produce meaningful biological activity. Whether a single infusion could eventually replace long-term medication will require substantially more evidence.
