How Gene Editing Saved A Baby, And A Baby Saved Gene Editing
In early 2025, the world watched as a baby named KJ became the first person ever treated with a fully personalized CRISPR gene-editing therapy. Born with CPS1 deficiency (a rare, life-threatening disorder that prevents the body from breaking down ammonia), KJ’s story is now a beacon of hope for families facing rare genetic diseases. But what really makes this moment historic isn’t just the science: it’s the promise of hope, of being able to make such treatments available and affordable for many more children in the years ahead.
KJ’s Story And Therapy
KJ’s treatment wasn’t a standard, off-the-shelf drug. Instead, it was a one-of-a-kind therapy designed specifically for his unique genetic mutation, and for him. After genetic testing at birth, scientists at Children’s Hospital of Philadelphia in the US, and the Innovative Genomics Institute (IGI) identified the exact DNA change causing his disease. In just six months they did something that usually takes years, they designed, manufactured, and delivered a custom CRISPR base-editing therapy.
But what about the cost? Traditionally, developing a gene-editing therapy for a single patient would be prohibitively expensive, around perhaps $15 million, plus three years of work. In KJ’s case, the cost was dramatically reduced because much of the work was done as a research collaboration, with companies contributing resources pro bono and regulatory agencies fast-tracking approval due to the urgent need. While an exact figure hasn’t been published, experts agree that as methods improve and more cases are treated, costs will drop significantly.
An In Depth Look At The Science
So how does all the science come together to save a child's life? Researchers mix the required components: an mRNA that encodes a "base editor" protein, the CRISPR component, and a guide RNA, responsible of getting the base editor to the right spot of KJ's DNA within his cells. Then, the components are mixed in a specific way with a lipid solution, which forms lipid nanoparticles (LNPs) containing the mRNA and guide RNA. The solution is treated to remove any leftovers of RNA and lipids not forming particles.
This LNP mix is then injected into KJ. While KJ's genetic disorder is in all of his cells, only the liver uses the protein encoded by the affected gene. The blood of KJ recognizes the lipids in the nanoparticles, and take them to the liver to be broken down, as if he had eaten a fatty meal. The liver cells absorb the LNPs, and break down the fatty components, releasing the RNAs into the cells.
There, the mRNA is expressed into a base editor protein. KJ's disease is caused by a single incorrect base in his DNA. Only 1 out of the 6.000.000.000 bases in his cells will cause the baby's death. But the base editor protein finds the exact place to be thanks to the guide RNA, an RNA strand complementary to the region of the gene with the mutation that acts as a GPS and chauffeur for the protein. Once in the right place, the base editor changes the wrong base for the correct one.
Suddenly, KJ's cells can now make the right protein, CPS1 enzyme, to break down ammonia! The leftover proteins and RNAs in his liver cells are eventually removed by the cells as they age, and KJ is now healthy and with no leftover damage from the treatment.
The scientists have now saved a life by changing a 2 nanometer building block inside his cells.
The $20 Million Bet: Making Personalized CRISPR Available for More Kids
Inspired by KJ’s success, the Innovative Genomics Institute (IGI) and the Chan Zuckerberg Initiative have launched a $20 million center dedicated to bringing custom gene-editing treatments to children with rare diseases. The goal is to create a pipeline that can rapidly design, test, and deliver therapies for “N-of-1” cases. These are patients with unique mutations that big pharmaceutical companies have little financial incentive to address, such as KJ.
This center isn’t just about treating a handful of children. The idea is to create a pipeline for therapies where the core components, like the mRNA backbone and delivery system, remain the same, and only the guide RNA is customized for each patient. This process can be streamlined and costs can be reduced further. Over time, this could make personalized gene-editing therapies accessible for thousands of rare diseases, most of which affect children and have no effective treatments today.
Why Lipid Nanoparticles Were Chosen Over AAVs
A key technical detail in KJ’s therapy was the use of lipid nanoparticles (LNPs) to deliver the CRISPR base editor to his liver cells. Why not use adeno-associated viruses (AAVs), which are common in other gene therapies?
LNPs are tiny fat bubbles that carry genetic material directly into cells. They are already used in mRNA vaccines and have a strong safety record. LNPs don’t integrate into the genome and are less likely to trigger immune reactions, making them a safer choice for in vivo (inside the body) gene editing, especially in children.
AAVs, on the other hand, are viral vectors that can efficiently deliver genes but have been linked to safety concerns, including immune responses and rare cases of cancer due to random integration into the host genome. These risks have led to regulatory caution, particularly for therapies intended for young or vulnerable patients.
By choosing LNPs, the team minimized potential long-term risks and set a precedent for future in vivo gene-editing therapies.
The Platform Approach: A Blueprint for the Future
Historically, regulatory agencies have required new approvals for each gene-editing therapy, even if only a small part of the treatment (like the guide RNA) changes. This made personalized therapies slow and costly. But now, there’s a shift toward a platform model: if the core technology is proven safe, only the targeting component needs to be customized and tested for each patient. This regulatory evolution is crucial for scaling up personalized medicine.
What’s Next?
KJ’s story is not just a one-off miracle. It’s the beginning of a new era where we get to target the smallest building blocks of life to rewrite the lives and stories of people. We can tackle rare genetic diseases one patient at a time, with therapies designed and delivered in months, not years. But, as impressive as that sounds, we are human. KJ's success story was all over the internet, and flew around the world to reach many scientists, researchers, and people involved in healthcare and innovation. Gene editing has been of interest for the last few decades, but the success of this one therapy might have done more to promote new therapies than many outreach campaigns, funding rounds, and so on. So, as much as gene therapies saved KJ, KJ might have saved gene therapies.
