Scientists in the US have attempted to edit a person’s DNA inside his own body, permanently altering his genetic code, according to The Associated Press. It will take at least a month, and as long as three, to know if the edit took. If it works, that may boost the development of gene therapies, which tinker with genes in order to treat or prevent diseases.
The patient, 44-year-old Brian Madeux, has a genetic disorder called Hunter syndrome: he lacks a key gene in his liver cells that breaks down complex molecules, which can then build up, causing damage to his body. The condition triggers infections, trouble breathing, as well as heart and brain problems. The therapy, part of a clinical trial run by Sangamo Therapeutics, involved giving Madeux a concoction that will eventually cut his DNA and insert the gene he's missing.
“We cut your DNA, open it up, insert a gene, stitch it back up. Invisible mending,” Sandy Macrae, president of Sangamo, told the AP. “It becomes part of your DNA and is there for the rest of your life.” The edit is permanent — which means permanent mistakes are a real risk — but Madeux, who’s already had 26 operations because of the debilitating disorder, says he’s willing to take the risk. “Hopefully it will help me and other people,” he told the AP.
This isn’t the first gene-therapy trial, but its method is different from previous attempts. In China, doctors took immune cells from a patient with aggressive lung cancer, edited them, and then injected the cells back into the patient to help defeat the disease. In that case, though, the editing happened outside the body, and used a gene-editing tool called CRISPR. Gene therapy has also been used to treat “bubble boy disease,” a severe immune system disorder that can cause an ordinary cold to become life-threatening. That used a virus to insert the genes, and sometimes resulted in leukemia.
The clinical trial taking place in California involves editing a person’s DNA inside their body. It also uses a different gene-editing tool called zinc finger nucleases. Like CRISPR, this tool can cut DNA, so that a corrective gene can be inserted into a specific spot in the genetic code. The same editing tool has already been used by Sangamo to edit the immune cells of HIV patients, though that editing was done outside the body.
The therapy is risky: patients who’ve had genes inserted into their DNA have died before. Editing mistakes might affect other genes or other parts of genome, causing cancer, for instance. “When you stick a chunk of DNA in randomly, sometimes it works well, sometimes it does nothing and sometimes it causes harm,” Hank Greely, a Stanford University bioethicist, told the AP. “The advantage with gene editing is you can put the gene in where you want it.”
For the treatment to succeed, only 1 percent of liver cells in Madeux’s body need to be edited with the new gene, according to the AP. If it’s successful, Madeux won’t need weekly enzyme infusions that cost between $100,000 to $400,000 he’s been taking to stave off the disease’s effects. A successful edit won’t completely cure him, but should prevent any further progression.
Sangamo hopes to eventually enroll nine to 12 other patients to test the treatment and see if it’s safe, says Edward Conner, Sangamo’s chief medical officer and senior vice president. If it works with Hunter syndrome, a similar therapy could be used for hundreds of other disorders caused by a mutation in a single gene, such as hemophilia B and PKU, Conner tells The Verge. “It’s really a transformational moment in my view,” Conner says.
The therapy holds the potential to change Madeux’s life forever — and that of thousands of other people. “I’m nervous and excited,” Madeux told the AP. “I’ve been waiting for this my whole life, something that can potentially cure me.”
Update November 15th, 2017 5:16PM ET: The story has been updated to include more information about the clinical trial and a quote from Edward Conner, Sangamo’s chief medical officer and senior vice president.