When KJ Muldoon was born in the summer of 2024, his parents were told he had a disease so rare, it strikes about one in 1.3 million newborns. His condition, a severe deficiency of an enzyme known as CPS1, left his tiny body unable to properly break down protein, flooding his blood with toxins that could cause brain damage or death. A liver transplant could correct the problem, but KJ was too young and too fragile to undergo one. With each passing day, the risk of irreversible neurological damage grew.
What happened next may become the most important medical story of the decade. In just six months, a team at Children’s Hospital of Philadelphia and Penn Medicine designed a personalized therapy that could correct the single misspelled letter in KJ’s DNA using a gene editing technology known as CRISPR. To get the therapy inside KJ’s cells, doctors relied on the same kind of mRNA technology that powered the Covid-19 vaccines. He received his first dose at 6 months old. One year later, KJ is walking, talking and thriving at home with his family.
We call them rare diseases, but there is nothing rare about the suffering they cause. Some 25 million Americans, nearly one in 13, live with rare genetic diseases. More than half are children, many of whom will not live to see their fifth birthdays. Families spend years searching for accurate diagnoses, cycling through misdiagnoses and facing financial ruin and isolation. And even though the direct medical costs of rare diseases are estimated at $400 billion a year, rivaling those for cancer and Alzheimer’s disease, fewer than five percent of them have Food and Drug Administration-approved treatments.
Why so few? Because the economics of drug development work against small patient populations. When a disease affects only a few hundred or a few thousand people, it’s hard to put together a clinical trial, and there is usually insufficient return on investment. Rare disease, in aggregate, is one of the largest unmet medical needs on earth.
What makes this moment different is that the technology to do something about it finally exists. Recent advances in mRNA science and CRISPR gene editing mean that the approach that helped KJ could be used for other children. The technology can be reprogrammed for different diseases by inputting a short stretch of genetic code that tells the molecular machinery exactly where to make its correction. Build the system once, and you can redirect it to a new disease by changing that one piece.
KJ’s doctors went to extraordinary, even heroic lengths to save him. They assembled a team across multiple institutions, compressed years of treatment development into months and secured authorization to administer the experimental therapy to KJ one week after the application was submitted to the F.D.A. But no health care system can rely on heroics for every patient. Even though the technology exists, there is no established pathway to do for the next child what was done for KJ, let alone for the thousands of other children who could benefit from this approach.
It is important to be honest about what this technology can and cannot do today. We know how to package mRNA in tiny fat bubbles and get it to the liver, which is where KJ’s cells were failing. Reaching other organs — the brain, the heart, the lungs — remains a significant scientific challenge. And for conditions caused by complex genetics rather than a single misspelled letter, the path forward is longer and harder.
I believe that the biggest obstacle, however, is structural. Our regulatory and commercial infrastructure was built for blockbuster drugs that treat millions of patients with the same pill. It was never designed for diseases for which each patient may need a bespoke correction to a unique mutation. But we already have a model for individualized, high-stakes interventions that correct specific defects in specific patients. We call it surgery. Consider a surgeon who performs a heart valve repair. No one asks that surgeon to run a clinical trial before operating on the next patient with a slightly different anatomy. The technique is validated, the facility is accredited, and each procedure is tailored to the individual. What if we started thinking of mRNA-CRISPR gene editing the same way — as molecular surgery, not as a pharmaceutical product?
There are promising signs that regulators and scientists recognize the problem. The F.D.A. recently proposed a new framework that would speed up the approval of individualized treatments for rare diseases by allowing regulators to evaluate these therapies based on evidence of how they work rather than requiring traditional large-scale clinical trials. Scientists are also working to build the infrastructure that could take advantage of these regulatory changes. The Children’s Hospital of Philadelphia and Penn Medicine plan to begin a trial that would repurpose the type of gene editor used for KJ to treat other patients. Johns Hopkins, where I work, has partnered with scientists at the Mayo Clinic and other collaborators to help found a group that aims to standardize manufacturing, share regulatory science and support clinical centers to deliver personalized therapies at scale.
But none of this is guaranteed. A key question is how the F.D.A. would enforce manufacturing standards for individualized treatments. If the standards are too onerous for each customized treatment, then the platform won’t be able to scale up. Even with the right regulatory framework, there would still need to be a commercial infrastructure to use it. No pharmaceutical company is going to build a manufacturing line for a disease that affects 12 people. Someone has to build the bridge between a one-off academic breakthrough and a repeatable clinical service, and right now there is little funding for that.
Radically new science demands radically new thinking about how we regulate, manufacture, pay for and deliver treatments. Ten years from now, if children are still dying of conditions we know how to correct, it will not be because the science wasn’t ready. It will be because we lacked the imagination to build a system worthy of it. KJ’s story is a miracle. But it should not remain a miracle. It should become a model.
Jeff Coller is a founder of the Alliance for mRNA Medicines and Rare RepairX, a consortium focused on personalized gene-editing technology for rare diseases. He also founded Tevard Biosciences, a company that develops RNA-based treatments for Duchenne muscular dystrophy using a different technology from the one described in this essay.
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