GoKawiilIn February, the US Food and Drug Administration (FDA) proposed a radical rethink of how scientists, physicians and manufacturers develop personalized genetic therapies. The regulator’s suggested introduction of a ‘plausible mechanism pathway’ should increase incentives for drug companies to develop personalized treatments, including gene-editing therapies for rare disorders (see go.nature.com/4mnmgzq).
The baby whose life was saved by the first personalized CRISPR therapy
Some 350 million people worldwide live with one of more than 5,000 genetic diseases1. Many of these conditions could, in theory, be treated with personalized therapies, which correct a single genetic mutation in a person’s DNA using the CRISPR gene-editing tool. In February 2025, KJ Muldoon, a baby born in the United States with a life-threatening metabolic disorder, became the first person to receive this type of personalized treatment2.
Yet, so far, the bespoke nature of such therapies has posed a huge obstacle to their spread. Much as a letter needs to be labelled with the right address, so CRISPR needs to be programmed to find and repair a mutation using a tiny string of nucleic acids called a guide RNA, which can be unique to each person. Under conventional rules, each guide RNA is therefore classed as a new drug, requiring stringent safety and efficacy testing and its own clinical trial.
In our work, we have found that it typically takes about four years to perform all the tests needed to get FDA approval for a tailored therapy. This lengthy period might be acceptable for a genetic treatment for a condition such as haemophilia or sickle-cell disease, for which existing medications can keep a person alive for many years. But it is much too long for a newborn who has been diagnosed with a severe genetic disease of metabolism, immune system, lungs or skin, for which treatment in the first year of life is crucial.
Worse, the full set of studies needed to secure approval to start a clinical trial is expensive, typically costing more than US$25 million. That’s too much for drug developers, for a product that will treat just one child.
Encouragingly, under the FDA’s proposed pathway, drug companies would be able to treat many people with different mutations as part of a single clinical trial — as long as participants have the same clinical symptoms, such as a disease of a specific metabolic pathway, or severe combined immune deficiencies. As a result, we foresee that the timeline to get CRISPR therapies into the clinic could drop to as little as three months, at a cost of less than $250,000 per patient.
Personalized gene editing helped one baby: can it be rolled out widely?
Only the first CRISPR therapy of the trial would need the full gamut of tests. Subsequent CRISPR gene editors, requiring only small changes from the first, would need just a few simple experiments to confirm that they did their job3,4. And if the first few editors in a trial worked well, the FDA could approve that type of CRISPR therapy to be made on demand, meaning that physicians could prescribe it to their patients5.
The regulator has shown the world the way forwards. Now, four key aspects of the drug development and approval process need updating, to make the most of this streamlined approval pathway.
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