Doctors say they constructed a bespoke gene-editing treatment in less than seven months and used it to treat a baby with a deadly metabolic condition.

The rapid-fire attempt to rewrite the child’s DNA marks the first time gene editing has been tailored to treat a single individual, according to a report published in the New England Journal of Medicine.

The baby who was treated, Kyle “KJ” Muldoon Jr., suffers from a rare metabolic condition caused by a particularly unusual gene misspelling.

Researchers say their attempt to correct the error demonstrates the high level of precision new types of gene editors offer. 

“I don’t think I’m exaggerating when I say that this is the future of medicine,” says Kiran Musunuru, an expert in gene editing at the University of Pennsylvania whose team designed the drug. “My hope is that someday no rare disease patients will die prematurely from misspellings in their genes, because we’ll be able to correct them.”

The project also highlights what some experts are calling a growing crisis in gene-editing technology. That’s because even though the technology could cure thousands of genetic conditions, most are so rare that companies could never recoup the costs of developing a treatment for them. 

In KJ’s case, the treatment was programmed to correct a single letter of DNA in his cells.

“In reality, this drug will probably never be used again,” says Rebecca Ahrens-Nicklas, a physician at the Children’s Hospital of Philadelphia who treats metabolic diseases in children and who led the overall effort to treat the child.

That effort involved more than 45 scientists and doctors as well as pro bono assistance from several biotechnology companies. Musunuru says he cannot estimate how much it had cost in time and effort.

Eventually, he says, the cost of custom gene-editing treatments might be similar to that of liver transplants, which is around $800,000, not including lifelong medical care and drugs.

The researchers used a new version of CRISPR technology, called base editing, that can replace a single letter of DNA at a specific location. 

Previous versions of CRISPR have generally been used to delete genes, not rewrite them to restore their function.

The researchers say they were looking for a patient to treat when they learned about KJ. After he was born in August, a doctor noted that the infant was lethargic. Tests found he had a metabolic disorder that leads to the buildup of ammonia, a condition that’s frequently fatal without a liver transplant.

In KJ’s case, gene sequencing showed that the cause was a misspelled letter in the gene CPS1 that stopped it from making a vital enzyme.

The researchers approached KJ’s parents, Nicole and Kyle Muldoon, with the idea of using gene editing to try to correct their baby’s DNA. After they agreed, a race ensued to design the editing drug, test it in animals, and get permission from the US Food and Drug Administration to treat KJ in a one-off experiment.

The team says the boy, who hasn’t turned one yet, received three doses of the gene-editing treatment, of gradually increasing strength. They can’t yet determine exactly how well the gene editor worked because they don’t want to take a liver biopsy, which would be needed to check if KJ’s genes have really been corrected.

But Ahrens-Nicklas says that because the child is “growing and thriving,” she thinks the editing has been at least partly successful and that he may now have “a milder form of this horrific disease.”

“He’s received three doses of the therapy without any complications, and is showing some early signs of benefit,” she says. “It’s really important to say that it’s still very early, so we will need to continue to watch KJ closely to fully understand the full effects of this therapy.”

The case suggests a future in which parents will take sick children to a clinic where their DNA will be sequenced, and then they will rapidly receive individualized treatments. Currently, this would only work for liver diseases, for which it’s easier to deliver gene-editing instructions, but eventually it might also become a possible approach for treating brain diseases and conditions like muscular dystrophy.

The experiment is drawing attention to a gap between what gene editing can do and what treatments are likely to become available to people who need them.

So far, biotechnology companies testing gene editing are working only on fairly common gene conditions, like sickle cell disease, leaving hundreds of ultra-rare conditions aside. One-off treatments, like the one helping KJ, are too expensive to create and get approved without some way to recoup the costs.

The apparent success in treating KJ, however, is making it even more urgent to figure out a way forward. Researchers acknowledge that they don’t yet know how to scale up personalized treatment, although Musunuru says initial steps to standardize the process are underway at his university and in Europe.