SHERIDAN, WYOMING – July 1, 2025 – A groundbreaking collaboration that delivered a custom-made CRISPR therapy to a nine-month-old patient with CPS1 deficiency has ignited optimism that ultrarare diseases could soon be addressed on a broader scale, thanks to advances in delivery systems, precision gene editing, and regulatory pathways.
KJ’s treatment—the first of its kind—was made possible through contributions from Acuitas Therapeutics, Aldevron, and Integrated DNA Technologies (IDT), which manufactured and shipped the key components free of charge. The success has prompted key industry figures to ask: can this model be repeated to address the thousands of ultrarare conditions affecting patients worldwide?
The Case for Platform Technologies
Tom Madden, president and CEO of Acuitas Therapeutics, told BioSpace, “But there’s a wide range of errors in factor VII [that cause hemophilia]. How do you serve a wide population with a single product? Realistically, you cannot do that.”
Madden recalled hearing former Center for Biologics Evaluation and Research (CBER) chief Peter Marks speak about platform technologies where the structural components of a therapy—like the delivery system—could be approved, while allowing for one part to be switched out. A genetic medicine approach could have a vector like an AAV or LNP, a guide molecule and a therapeutic payload approved as a platform. To treat a patient with a unique, so-called “n of 1” disease, a custom guide could be created and plugged into an already approved platform technology.
Madden explained that Marks was “quite fulsome” about the possibilities of facilitating treatments for rare and genetic conditions. At the time BioSpace spoke with Madden, May 23, it was not clear whether Marks’ successor, Vinay Prasad, would deviate from this vision.
So far, he hasn’t: two weeks later, the FDA granted the first ever Platform Technology Designation to Sarepta Therapeutics for a viral vector called rAAVrh74 that the company uses with a variety of the treatments it is developing. The designation, developed under the Biden administration, is seemingly the first step toward fulfilling recent promises by new CBER Director Vinay Prasad, FDA Commissioner Marty Makary and HHS Secretary Robert F. Kennedy Jr. to make treatments for genetic and rare diseases easier to develop.
Precision Gene Editors Enable Tailored Therapies
John Evans, CEO of genetic medicines company Beam Therapeutics, told BioSpace, “It’s not surprising to me that we haven’t been able to do this before. We need certain capabilities and we’re just now getting to the point where [treating ultrarare diseases] is plausible.”
Evans described the limitations of older technologies: “Older tools could go anywhere, but all they could do is make a cut, including in CPS1,” he said. “In CPS1, just cutting it isn’t going to help; the gene is broken.”
He explained how new precision editors made KJ’s treatment possible: “The original Cas9 wasn’t versatile.” And, highlighting the advantage of the new approach, Evans said, “It’s like a pencil and eraser. It’s known as gene editing 2.0 for a reason.”
Strategic Advantages of Lipid Nanoparticles
Isaac Hilton, a bioengineer at Rice University, emphasized the advantage of treating liver-based diseases: “Liver-based conditions are advantageous in these kinds of rare diseases.”
Evans also discussed challenges: “Cas9 is a large protein. It’s not trivial to get it to the right place.”
He noted why KJ’s treatment used lipid nanoparticles: “I’m not surprised [KJ’s treatment] used LNPs, they’re much more straightforward and easier to manufacture,” Evans said.
Challenges and the Regulatory Landscape
While KJ’s treatment got fast-tracked through the FDA with interventions from organizations like the Innovative Genomics Institute and Danaher, Evans expressed optimism for the future: “We are thinking about getting involved in these n of 1 cases,” Evans said of Beam. “It should absolutely be achievable to get people in a clinic, as long as it’s in an organ we can target. Start in the liver, maybe go to the blood. It’s not that hard to do anymore.”
These developments suggest a turning point in the quest to deliver life-changing treatments to patients with ultrarare diseases, as technology, manufacturing strategies, and regulatory support converge.
Learn more at BioSpace.com.