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.”
