Molecular surgery: How Europe can lead the world

In February 2025, an infant named KJ Muldoon received a CRISPR gene-editing therapy built for him alone. He had been born with CPS1 deficiency, a severe urea cycle disorder that left his body unable to clear the toxic ammonia that protein produces. A team at Children’s Hospital of Philadelphia and the University of Pennsylvania designed his correction in months: an mRNA-encoded base editor, delivered to his liver inside a lipid nanoparticle and carrying a short custom guide that aimed it at his exact mutation. The therapy worked, and he is alive and developing. 

The achievement was extraordinary and unrepeatable. Every step required improvisation that no existing regulatory or reimbursement system was designed to support. That is the problem now facing genetic medicine. Thousands of children are born each year with mutations so rare that each may be the only patient who has one, and none will ever attract a commercial drug program. The science to correct many of them already exists. What does not exist is a system to deliver those corrections at scale.

The reason is structural. Regulators on both sides of the Atlantic treat every personalized gene-editing therapy as a new pharmaceutical product, each requiring its own manufacturing validation, its own clinical evidence package, its own regulatory review, and its own multi-year timeline. That model works when one medicine serves millions of patients. It breaks when one medicine serves one. The US Food and Drug Administration’s drug center clears about fifty new medicines a year, and its biologics center fewer than ten cell and gene therapies. No regulator at that throughput can review thousands of bespoke therapies as individual products. There is a better model, and medicine has relied on it for over a century. We do not regulate each surgical operation as a new product. We validate the technique once. We accredit the institutions allowed to perform it and credential the surgeons who carry it out, then trust them to adapt a proven method to the patient in front of them.

mRNA-CRISPR technology can be regulated the same way. I call it molecular surgery. The editing platform, the delivery system, the manufacturing process, and the safety profile are validated once. Only the short targeting sequence that points the editor at a particular mutation changes  from one patient to the next. In KJ’s case, every component was standard except that guide. The bespoke sequence is the molecular equivalent of where a surgeon makes the incision, and it should be authorized as a medical act under professional governance rather than resubmitted as a new drug each time.

Not every genetic therapy qualifies as molecular surgery, and one property is essential: transience. The intervention must correct its target and then clear the body rather than persist in it. The approach suits a single, well-characterized error a validated editor can reverse in a tissue the delivery system can reach, and it cannot address damage that lies beyond a single edit, such as large chromosomal rearrangements or disease spread across many genes.

This is why mRNA delivery is the genius of the approach. The mRNA instructs the cell to build the editor and then clears within days. The correction it makes is permanent, but the tool that made it is gone, leaving nothing written permanently into the genome, as a viral vector would. A treatment that erases itself can be re-dosed and avoids a whole category of long-term risk. A surgeon operates and then leaves the body to heal. mRNA does the same at molecular scale.

Building this will take more than regulators. It needs a professional body to set the technical standards and clinical guidelines, and to bring developers and regulators to the same table, the way medical societies have always governed new techniques. The Society for RNA Therapeutics and the Alliance for mRNA Medicines, two global networks of scientists and physicians on whose board I serve, were founded to provide exactly that leadership for the RNA field. Their combined missions are to set manufacturing standards and clinical guidelines, and to broker the public-private-regulatory partnerships these therapies depend on, which is the connective tissue molecular surgery will require. Under that kind of leadership, each patient’s therapy could be authorized through accredited Certified Molecular Surgery Centers that hold validated inventory and perform the procedure under long-term follow-up, reimbursed as a procedure on the model of transplantation rather than as a packaged product.

This is where Europe has an opening. The next phase of genetic medicine will be decided by who builds the system to deliver these therapies safely and at scale, and that contest is wide open. It is one Europe can win.

Europe may even be better positioned than the United States, because it has already written a version of this principle into law. Under the hospital exemption in its advanced-therapy regulation, a hospital can prepare a custom advanced therapy for a single patient, on a physician’s responsibility, without the full marketing authorization a mass-market product requires. Its weakness is that the exemption is governed country by country, with diverging standards and no shared infrastructure behind it. The opportunity is to harmonize it into a single European definition of molecular surgery, backed by a network of accredited centers held to common standards and a shared outcomes registry. Reimbursement would remain a national decision, but member states could agree to pay for the procedure rather than the product, as they already do for transplantation. Whoever builds this system first will set the standard the rest of the world adopts.

KJ Muldoon’s story has been called a miracle. The harder and more important work is to make it a model, so that the next thousand children do not need a miracle to survive. The technology is arriving. Whether it reaches patients depends on whether we are willing to redesign the system that delivers it, and Europe should choose to be the place that does.

About the author:  Jeff Coller is the Bloomberg Distinguished Professor of RNA Biology and Therapeutics and director of the RNA Innovation Center at Johns Hopkins University. He serves on the board of the Society for RNA Therapeutics and is a co-founder of the Alliance for mRNA Medicines and Tevard Biosciences.