Base editors can modify a DNA sequence (shown here in a coloured autoradiogram) at specific target sites, allowing disease-causing mutations to be corrected.Credit: Hank Morgan/Science Photo Library
Late last year, dozens of researchers spanning thousands of miles banded together in a race to save one baby boy’s life. The result was a world first: a cutting-edge, gene-editing therapy fashioned for a single person, and produced in a record-breaking six months1.
Now, baby KJ Muldoon’s doctors are gearing up to do it all over again, at least five times over. And faster.
The groundbreaking clinical trial, described on 31 October in the American Journal of Human Genetics2, will deploy an offshoot of the CRISPR–Cas9 gene-editing technique called base editing, which allows scientists to make precise, single-letter changes to DNA sequences. The study is expected to begin next year, after its organizers spent months negotiating with US regulators over ways to simplify the convoluted path a gene-editing therapy normally has to take before it can enter trials.
Developing KJ’s treatment was “a pretty hectic and intense six months”, says Kiran Musunuru, a cardiologist at the Perelman School of Medicine at the University of Pennsylvania in Philadelphia, and one of KJ’s doctors. “But I think we can get it shorter.”
CRISPR genome-editing grows up: advanced therapies head for the clinic
The trial is also the next step towards answering a question that has hung over many families of children with rare diseases since the news broke of KJ’s successful treatment: when will it be our turn? “There is no ‘one size fits all’ in this space,” says Ryan Maple, executive director of the Global Foundation for Peroxisomal Disorders in Tulsa, Oklahoma.
Momentum seems to be building. In addition to the planned clinical trial in Philadelphia, the Center for Pediatric CRISPR Cures, which launched in July at the University of California, Berkeley and the University of California, San Francisco, also aims to develop personalized gene-editing therapies. And in September, the US government’s Advanced Research Projects Agency for Health announced two programmes to fund research into the development and manufacturing of “precision genetic medicine”.
“I’m more optimistic now than I have been in the past,” says Joseph Hacia, a medical geneticist at the Keck School of Medicine at the University of Southern California in Los Angeles.
Therapy for one
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