“I went to Fyodor and said, ‘Hey, we’re getting all these good results in the clinic with CRISPR, but why isn’t it scaled up?’ Hu says. One reason for this is that most gene-editing companies are pursuing the same few conditions, such as sickle-cell, where (as luck would have it) the same edit works for all patients. But that doesn’t leave much hope for the roughly 400 million people who have 7,000 other inherited diseases to fix their DNA, Urnov estimated in his editorial.
Then, last May, came the dramatic demonstration of the first completely “personalized” gene-editing treatment. A team in Philadelphia, with the help of Urnov and others, succeeded in correcting the DNA of a child named KJ Muldoon, who had a completely unique mutation that caused a metabolic disease. Although it did not target PKU, the project showed that gene editing could theoretically cure some inherited diseases “on demand.”
It also highlighted a bigger problem. Treating a single child requires a large team and costs millions in time, effort and materials – all to create a drug that will never be used again.
The new “umbrella” tests should detect exactly this type of situation. Kiran Musunuru, who co-led the team at the University of Pennsylvania, says he has been in discussions A study of bespoke gene editors focusing on Baby KJ’s diseases, called urea cycle disorders, will be launched this year in collaboration with the FDA. Every time a new patient comes forward, he says, they will immediately try to design a variant of their gene-editing drug that is tailored to fix that child’s particular genetic problem.
Musunuru, who is not associated with Aurora, does not think the company’s plans for PKU count as fully personalized editors. “These corporate PKU efforts have nothing to do with Baby KJ,” he says. He says his center continues to focus on the mutation “is so rare that we don’t see a scenario where a for-profit gene-editing company would consider that indication commercially viable.”
Instead, what’s happening in PKU, Musunuru says, is that researchers have realized they can assemble “a set” of the most frequently occurring mutations in a large enough group of patients to make PKU therapy commercially viable.
Although this would still miss many patients with extra-rare gene errors, Musunuru says any gene-editing treatment would still be “a vast improvement over the status quo, which is zero genetic treatments for PKU.”
