The method called prime editing can make fine-scale edits to DNA (artist’s illustration).Credit: Patrick Landmann/Science Photo Library
A powerful gene-editing technique has been used to edit DNA directly in a person’s body — the first known instance of such a treatment.
The milestone treatment is part of a clinical trial of prime editing, a technique that can alter DNA with more precision than standard CRISPR–Cas9 methods can. In this case, prime editing was used to treat a condition called Wilson disease by rewriting DNA in liver cells, to erase a mutation that prevents them from eliminating excess copper.
Prime Medicine, a biotechnology company in Cambridge, Massachusetts, announced that it had treated the first person in its trial earlier this month. It expects to announce the first results from the study next year.
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“I never dreamed that in my lifetime I would see this applied to my rare disease,” says Rhonda Rowland, president of the Wilson Disease Association in Atlanta, Georgia. “It’s going to be a really exciting year.”
In launching the trial, Prime Medicine joins a host of companies aiming to engineer cells directly in the body, rather than using the standard method of extracting a person’s cells, editing their DNA in a laboratory and then reinjecting the altered cells. Rewriting DNA in the body, or in vivo, is appealing because manufacturing and administering the treatment might be much cheaper and faster than making a bespoke therapy for each person from their own cells.
But in vivo approaches have their own challenges, says Krishanu Saha, a biomedical engineer at the University of Wisconsin–Madison. “It depends on what types of risks you’re willing to accept,” he says.
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Wilson disease is caused by mutations in a gene called ATP7B, which encodes a protein that transports excess copper out of the liver. If left untreated, the resulting build-up of copper can cause liver and nerve damage, as well as neurological disorders.
People with Wilson disease are eager for a one-and-done treatment for their condition, says Rowland, rather than the current, complicated regimen of copper-clearing molecules and other medicines. And gene editing could, in theory, provide a lasting solution by correcting the faulty ATP7B gene.
So far, the US Food and Drug Administration (FDA) has approved only one gene-editing therapy, called Casgevy, which is used to treat two inherited blood disorders. Casgevy relies on CRISPR–Cas9 gene editing, which is often used to disable genes rather than to rewrite their sequences.
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Another form of gene editing, called base editing, can rewrite individual DNA letters, but cannot make the particular corrections needed to fix the most common ATP7B mutations. That left prime editing, a more complex and versatile system that can insert, delete and rewrite segments of DNA. In another clinical trial, Prime Medicine used the technique to treat two people with a rare immune disorder, by rewriting DNA in each participant’s blood stem cells outside of the body and then injecting them back in.
So far, no gene-editing therapies have been approved for use in vivo. But the FDA is expected to issue a decision early next year about an in vivo CRISPR–Cas9 therapy for a condition called hereditary angioedema, which causes severe swelling.