First Baby in the World Cured with Personalized Gene Editing

Little KJ can finally live at home with his parents and siblings, after spending the first nine months of his life hospitalized, on a diet and under close observation, due to a serious, incurable and potentially lethal metabolic disease. Everything changed when he became the first patient in the world to experience a new therapy based on personalized gene editing with Crispr technology: between February and April he underwent three infusions and after a few weeks he already showed some signs of improvement, without serious side effects. The result, which opens up new scenarios for rare genetic diseases, was published in the New England Journal of Medicine by a team from the Children's Hospital of Philadelphia and the University of Pennsylvania.

Technique already used for sickle cell anemia

"This is an important step forward that will allow us to cure diseases that were incurable until now," says geneticist Giuseppe Novelli of the University of Rome Tor Vergata. "Gene editing with Crispr is already used clinically today on patients with sickle cell anemia and beta-thalassemia, diseases caused by fairly frequent mutations that affect hundreds or thousands of people. In this case, however, we have a personalized approach based on a technological platform that will make editing easier on diseases linked to rarer genetic variants."

A road that seemed difficult to travel

Little KJ, who led the way, was born with a rare metabolic disease due to a deficiency of a liver enzyme, carbamoyl phosphate synthase 1 (CPS1): this condition causes ammonia to accumulate in the blood to toxic levels, with serious consequences for crucial organs such as the brain. "Treating this disease with gene editing seemed very complicated until now for two reasons," explains Novelli. "First, the liver is not easy to reach, unlike other organs such as the eye or blood. Second, its cells proliferate enormously during growth and, if you don't have a highly efficient technique for delivering the correct gene, you risk it not being transmitted to all the daughter cells."

The solution at the moment

The only solution at the moment is to reduce the protein in the diet while waiting for the liver transplant, which however can only be accessed by clinically stable patients who are old enough to undergo such a major procedure. And while waiting there is always the risk that hyperammonemia could cause permanent neurological damage or even lead to death.

The therapy was developed in six months

Given KJ’s tender age, researchers attempted to help him by developing a personalized gene-editing therapy that targeted the specific CPS1 gene variant identified in the baby shortly after birth. Drawing on years of preclinical research on similar diseases, the therapy was developed in just six months and administered via lipid nanoparticles infused in three doses, in February, March, and April 2025. In the short time since the treatment, KJ tolerated increased protein in his diet and required fewer medications to treat ammonia buildup. He also recovered from some common childhood illnesses, such as rhinovirus, without ammonia building up in his body.

The results look promising

“Although KJ will need to be monitored closely for the rest of his life, our initial results are quite promising,” says Rebecca Ahrens-Nicklas , director of the Gene Therapy for Inherited Metabolic Disorders Frontier Program at Children’s Hospital of Philadelphia and associate professor of pediatrics at the University of Pennsylvania. “We hope other researchers will replicate this approach for many rare diseases, giving many patients a real chance at living healthy lives,” adds Kiran Musunuru , a translational medicine expert at the University of Pennsylvania. “The promise of gene therapy that we’ve been hearing about for decades is coming to fruition, and it will fundamentally transform our approach to medicine.”