What was long considered a vision of the future has become reality: a gene therapy developed for a single person. The case of little KJ from Philadelphia has changed the debate about rare diseases – and prompted the US Food and Drug Administration (FDA) to create a new approval pathway.
The case of KJ
KJ was born with severe CPS1 deficiency, an extremely rare metabolic disorder in which toxic ammonia accumulates in the blood. Many affected children do not survive the first months of life or require a liver transplant. Within around six months, a team in Philadelphia developed a CRISPR therapy tailored to KJ’s individual mutation, which was delivered directly to the liver in lipid nanoparticles. The FDA approved its use in an expedited procedure. The case was published in the New England Journal of Medicine in May 2025. KJ received a total of three doses, was able to go home and is developing well.
The problem: approval for a single patient
Conventional approvals are based on large, controlled trials. For diseases that affect only a handful of people worldwide – or for mutations carried by only one person – this is impossible. So far, such therapies have therefore remained individual cases with special authorisation.
The FDA’s answer: the “Plausible Mechanism Framework”
In February 2026, the FDA published draft guidance for individualised therapies for rare genetic diseases. The idea: a platform – such as a particular CRISPR technology with a fixed delivery system – is tested in a single trial, while the “target sequence” is adapted for each patient. Prerequisites include:
- a known genetic cause of the disease,
- a well-described natural course of the disease without treatment,
- proof that the target gene has actually been modified,
- and a measurable clinical improvement.
The UK regulator MHRA has also announced similar plans for platform technologies.
Opportunities and open questions
For families with ultra-rare diseases, the new pathway could mean the difference between “no treatment” and “timely treatment”. Critics point out, however, that less trial data also means less knowledge about rare side effects. There are also unresolved questions of funding: who pays for a therapy that is manufactured only once? And what structures are needed so that it is not just children at a few top centres who benefit?
Further headwinds come from research funding: in the USA, thousands of grant projects of the National Institutes of Health (NIH) and the National Science Foundation (NSF) were halted in 2025, and many biotech companies have cut staff.
Conclusion
The case of KJ shows how fast modern gene editing can be. Whether this becomes a reliable route to care now depends on regulation, funding and the long-term data of the first patients.
Note: This article is for general information only and does not replace medical advice.
