In mid-2024, little KJ arrived in the world, and Nicole and Kyle were thrilled until routine tests showed something was terribly wrong. His blood also was carrying dangerously high ammonia levels. KJ was very nearly taken from his first breath by a rare inherited disorder that could have meant his death. The cause: A single gene with an error so minuscule it wasn’t found until ahead of those first screenings. Carbamoyl phosphate synthetase 1 deficiency, or CPS1 deficiency, means standard treatments for babies who are born with this problem often only eventually provide a break. Only a liver transplant will keep them alive, and even that comes with a life of complications when things are really bad.
What is CRISPR?
CRISPR, or Clustered Regularly Interspaced Short Palindromic Repeats, is a bit of a mouthful, but essentially it’s a brilliant system pilfered from bacteria. Microbes use CRISPR to identify invading viruses: they cut out viral DNA and keep bits in their own genetic makeup, essentially a “most-wanted” list. If the same virus attempts to invade again, the bacteria rapidly mobilize molecular scissors (driven by the cached snippets) to slash the invader’s DNA to bits. Scientists leveraged this defense strategy to create a gene-editing toolkit. By crafting a bespoke RNA guide, scientists can instruct the system to target nearly any sequence in the genome. A specialized enzyme—in most cases Cas9 or one of its variants—then slices the DNA at that exact location. There, the cell’s own repair mechanism can be tricked into repairing the break, either shutting down a gene or replacing it with a corrected copy. In the past decade, CRISPR has revolutionized genetics research, turning once-formidable experiments into routine—and even sparking talk of cures once deemed impossible.
What is CPS1 deficiency?
Imagine your body as a factory processing nutrients. Part of that job involves converting harmful waste—ammonia—into urea, which our bodies excrete safely. The enzyme CPS1 kick-starts this process. Ammonia levels build up in the bloodstream when CPS1 is missing or doesn’t work properly because of a genetic defect, and it poisons the brain to different degrees, depending on the severity of the defect. Symptoms in infants include lethargy, poor feeding, and seizures that begin in the first days of life. Without treatment, infants with untreated CPS1 deficiency are often fated to endure permanent brain injury or death. Pure diet (low-protein diet), medications that bind ammonia, and dialysis offer some benefits but do not replace the missing enzyme. A liver transplant is a definitive cure, but it comes with surgical risk, life-long immunosuppression, and donor availability concerns. Families such as KJ’s often endure a sense of forever waiting for a viable liver.
The Search for a Solution
Faced with these daunting facts, KJ’s medical team at the Children’s Hospital of Philadelphia refused to settle for good enough. Led by Dr. Rebecca Ahrens-Nicklas and geneticist Dr. Kiran Musunuru, the researchers proposed a bold plan: create a one-of-a-kind gene-editing treatment tailored just to KJ’s DNA. Rather than shutting down a gene broadly, they aimed to correct the precise mutation at fault in his CPS1 gene. This was uncharted territory—no human had ever received a bespoke CRISPR therapy designed solely for their unique genetic code.
Developing a Personalized Therapy
Turning this vision into reality took hundreds of painstaking steps. First, scientists sequenced KJ’s entire genome to pinpoint the exact letter in his DNA that was wrong. Next came the design of a “base editor,” a gentler cousin of the original CRISPR/Cas9 system. Instead of chopping both strands of DNA, the base editor chemically converts one nucleotide to another—like changing a single letter in an instruction manual without tearing the page. Armed with this precision tool, the team packaged the editor into tiny fat-bubble carriers called lipid nanoparticles. These particles would ferry the base editor through KJ’s bloodstream and deposit it directly into his liver cells, where CPS1 normally resides.
Administering the Treatment
In February 2025, at just six months old, KJ became the first infant ever to receive a tailored gene-editing infusion. For safety, doctors started with a low dose, watching his vital signs around the clock. Within days, blood tests showed a dramatic shift: ammonia levels steadied, no longer soaring to the rogue peaks that had put him at risk of brain injury. Encouraged, the team followed up with two higher-dose infusions to reinforce the correction. Through every step, KJ’s parents were by his side, marveling as his color improved, his energy returned, and his tiny body began to thrive.
Monitoring Progress
Since his initial treatment, KJ’s development has been nothing short of astonishing. He’s hitting milestones on track—rolling over, babbling with newfound gusto, and even testing the limits of his newfound strength by pulling himself to stand. Hospital visits are now rare check-ins rather than emergency interventions. While he still takes a few supportive medications and undergoes periodic blood work, the specter of impending liver transplant surgery has lifted. For the first time, his family can envision a future unshadowed by constant medical crises.
Implications for Personalized Medicine
KJ’s success is more than a single triumph; it marks the dawn of a new era in medicine. Rather than one-size-fits-all therapies, we can now imagine treatments custom-crafted for each patient’s genetic quirks. Rare diseases—once dismissed as hopeless—could be squarely in the crosshairs of science. Although this approach will not replace standard care for common conditions anytime soon, it opens doors for families grappling with pediatric disorders inherited from birth. In clinics around the world, researchers are already identifying other candidates whose mutations might be amenable to similar fixes.
A Collaborative Effort
Behind every milestone lies a vast network of coordination. Laboratory scientists synthesized the base editors. Preclinical teams verified safety in animal models. Under every milestone are all the supports, trade-offs, and coordination. The base editors were synthesized by laboratory scientists. Safety was confirmed in animal models by preclinical teams. But biomanufacturing experts scaled up production, and each batch had to meet stringent quality standards. Food and Drug Administration regulatory advisors took it a step further and worked hand in hand with them to adapt existing pathways and expedite review, but with the tightest safety benchmarks. Nurses, pharmacists, ethicists, and a million support staff rose around KJ and his family, showing the power of a team in a life-or-death situation.
Looking Ahead
While KJ’s story is extraordinary, he is not unique. Genetic sequencing now uncovers the roots of countless rare diseases. As the cost of personalized therapies comes down and manufacturing processes become more streamlined, dozens of infants each year may benefit from treatments once confined to the realm of science fiction. Challenges remain—long-term safety, equitable access, and ethical considerations will demand careful navigation—but KJ’s shining example shows us what’s possible when innovation and compassion combine.
From the first anxious days after birth to his latest delighted giggles, KJ’s journey illuminates a powerful truth: by rewriting a single letter in a life’s instruction manual, we can change a destiny once thought sealed. In doing so, we’ve opened the door to hope for countless others who await their own shot at a healthy future.
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