The method called master 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 case of such a treatment. This landmark treatment is part of a clinical trial of primary editing, a technique that can alter DNA more precisely than standard CRISPR-Cas9 methods. In this case, master editing was used to treat a condition called Wilson’s disease by rewriting the DNA in liver cells to erase a mutation that prevents them from removing excess copper. Prime Medicine, a biotechnology company in Cambridge, Massachusetts, announced that it had treated the first person in its trial earlier this month. He hopes to announce the first results of the study next year. Bigger than CRISPR? A guide for the latest genome editors“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.” By launching the trial, Prime Medicine joins a number of companies that aim to engineer cells directly into the body, rather than using the standard method of removing a person’s cells, editing their DNA in a lab, and then reinjecting the altered cells. Rewriting DNA in the body, or in vivo, is attractive because manufacturing and administering the treatment could be much cheaper and faster than making a personalized 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 the type of risks you are willing to accept,” he says. Prime Time Wilson’s 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 copper buildup can cause liver and nerve damage, as well as neurological disorders. People with Wilson’s disease are eager for a single treatment for their condition, Rowland says, rather than the current complicated regimen of copper-cleansing molecules and other medications. And gene editing could, in theory, provide a lasting solution by correcting the defective ATP7B gene. So far, the U.S. Food and Drug Administration (FDA) has approved only one gene-editing therapy, called Casgevy, which is used to treat two inherited blood disorders. Casgevy is based on CRISPR-Cas9 gene editing, which is often used to disable genes rather than rewrite their sequences. A rare CRISPR enzyme kills cancer cells by shredding their DNA. Another form of gene editing, called base editing, can rewrite individual letters of DNA, but it cannot make the particular corrections needed to correct the most common ATP7B mutations. That left core 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, rewriting the DNA in each participant’s blood stem cells outside the body and then injecting them back inside. 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 on an in vivo CRISPR-Cas9 therapy for a condition called hereditary angioedema, which causes severe inflammation.
