As cell and gene therapy leaders gathered in Maryland to discuss accelerating clinical trials in children, one “cutting edge” session focused on the need to expedite more bespoke gene editing treatments like the one that saved young KJ Muldoon.
Nearly a year after Baby KJ Muldoon received the first-ever personalized CRISPR treatment, scientists are gearing up to do it again. A team at the Innovative Genomics Institute, founded by CRISPR pioneer Jennifer Doudna, hopes to soon embark on a trial to treat a child born with another disease caused by an inborn error of immunity, according to a recent talk by Fyodor Urnov, the institute’s director of Therapeutic R&D.
“They’re trying to make CRISPR, in this case, base editing RNAs, customized to each patient, in real time almost,” Robert Sikorski, chief medical officer at Immusoft who spoke at an April 9 gathering of cell and gene therapy leaders at FDA headquarters, told BioSpace. Of all the sessions at the workshop, Sikorski continued, Urnov’s presentation on N of 1 trials for personalized therapies was “the cutting edge of the cutting edge of the cutting edge,” he said.
By now, most people in the scientific community—and many outside of it—know the story of KJ Muldoon, a nine-month-old boy suffering from CPS1 deficiency, an extremely rare and potentially fatal genetic condition. Last May, he was treated with a CRISPR treatment designed just for him, and today, KJ “is thriving,” Jeff Coller, director of the RNA Innovation Center at Johns Hopkins University, wrote in a recent opinion piece in The New York Times. He’s also become a poster child for bespoke gene editing therapies.
A November 2025 article by FDA Commissioner Marty Makary and Center for Biologics Evaluation and Research (CBER) head Vinay Prasad introducing the agency’s plausible mechanism pathway cited KJ as an example of what this program could make possible. The pathway seeks to accelerate gene and gene editing therapies for diseases affecting exceedingly small patient populations where a randomized trial would not be feasible.
Biopharma is all in too. In January, a group of CRISPR pioneers, including Doudna, debuted Aurora Therapeutics. Its goal: to develop the industry’s first platform technology that can reliably and repeatedly produce gene therapies to address rare disease-causing mutations.
But it’s early days. The landscape is untested; so, largely, are the rules and regulations, and Aurora seeks to succeed where another bespoke startup failed earlier this year.
Not far enough
In March, EveryONE Medicines announced it would close its doors, with an anonymous source telling Endpoints News the decision was due to shortcomings in the plausible mechanism pathway.
The biotech’s decision was somewhat surprising, in that it came just a week after the FDA offered new details on that pathway. But according to a person familiar with the matter who spoke to Endpoints, the much-anticipated draft policy did not go far enough to enable feasible commercialization of bespoke therapies. The company had been hoping for a process-level approach, similar to that of the U.K. pilot, which allows for easier regulatory submissions for different drugs that use the same processes. EveryONE received approval for its drug testing and manufacturing processes under this program. Conversely, under the plausible mechanism pathway, each drug will require a discrete application, with a submission package built from the ground up.
“Under classic paradigms, you have one mutation, one gene, one disease, one drug product, one IND,” Urnov said during his presentation, but such regulatory redundancy can become burdensome, especially when targeting diseases that can be caused by more than one mutation.
Urnov and his team are planning to initiate a trial at the University of San Francisco California (UCSF) by the end of this year for a child with familial hemophagocytic lymphohistiocytosis (HLH), a rare genetic disorder triggered by a genetic error that affects immunity. HLH is caused by mutations in one of six genes in the granzyme relief pathway, Urnov explained. “We need to be able to have multiple guide RNAs, multiple editors on the same IND,” he explained.
Furthermore, “if this is a clinical syndrome where we have six different genes that cause the same disease, could we not have a master clinical protocol? Yes, we can.”
The right direction
The FDA has made strides toward such a framework for certain gene therapy platforms. In June 2025, Sarepta Therapeutics won the agency’s first Platform Technology Designation for the viral vector, rAAVrh74, which it uses in its gene therapies. Companies that obtain this designation can use a “platform technology” to make more than one drug or biologic, with the aim of streamlining reviews and creating predictability for new drug applications based on the same technologies, according to draft guidance issued in 2024.
The FDA pulled Sarepta’s designation after three patients taking therapies containing rAAVrh74 died last year. The agency awarded a second platform technology designation in October to Krystal Biotech for the company’s non-replicating HSV-1 viral vector.
Coller in his NYT piece suggested another potential model to expedite and expand the number of personalized gene editing treatments. “We already have a model for individualized, high-stakes interventions that correct specific defects in specific patients,” he wrote. “We call it surgery.”
Coller offered the example of a surgeon who performs heart valve repairs on two different patients. “No one asks that surgeon to run a clinical trial before operating on the next patient with a slightly different anatomy,” he wrote. “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, he proposed.
One in 10 Americans lives with a rare disease, according to the National Organization for Rare Disorders. Half of these patients are children. Many gene therapies in development are intended for these indications.
“I think it’s critical that we address drug development for children, always attending to science and clinical unmet need,” Neurogene regulatory chief Andrew Mulberg said on April 9 during his presentation on Rett Syndrome.
On this note, the call for increased data sharing in cell and gene therapy has gained traction in recent months, both with the plausible mechanism pathway and the FDA’s first-ever public town hall on the issue last Fall.
“In the world of gene therapy, we need to do a better job about sharing information across our sector,” Mulberg told attendees at the pediatric CGT meeting. “I really wish and ask the agency to take a more proactive role in generating a pathway to be able to share those data.”
