Gene-Editing Breakthrough Saves an Infant with a Rare Disease

Gene-Editing Breakthrough Saves an Infant with a Rare Disease

I have written several times about the gene-editing technology called CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats), which allows scientists to precisely modify the DNA of living organisms.

Originally discovered as part of a natural immune system in bacteria, CRISPR has been adapted as a powerful tool for genetic engineering across a wide range of species. My more recent articles have focused on the creation of Argentinian “super-horses” and the hyped-up accounts of “extinct” dire wolves returning to life.

The technology can also be applied to humans and, if done with circumspection, can be a powerful tool to achieve miraculous cures. A perfect example of the possibilities of CRISPR came to light when news of a historic medical breakthrough was made after a nine-month-old baby became the first person in the world to be successfully treated with a personalized gene-editing therapy for a rare and life-threatening genetic disorder.

K.J. lacked an enzyme in his liver that normally converts ammonia—produced when proteins break down in the body—to urea that the body excretes. Ammonia builds up in the body and damages organs, particularly the brain and liver. Without this treatment, he would have needed a liver transplant.

“He was a very sick baby,” said Dr. Rebecca Ahrens-Nicklas, K.J.’s physician and director of an inherited metabolic disorders program at Children’s Hospital of Philadelphia.

K.J. was also lucky. Ahrens-Nicklas and colleague Dr. Kiran Musunuru, professor for translational research at Penn Medicine, had been working on ways to correct genetic mutations in young children with ultrarare diseases.

Their research helped them create and win regulatory approval for a custom Crispr therapy for K.J. in six months—a process that can otherwise take years. Between February and April, K.J. received three doses of the therapy, delivered by lipid nanoparticles to the liver to correct his disease-causing mutation.

The initial results look promising.

As of April 2025, KJ had received three doses of the therapy with no serious side effects. In the short time since treatment, he has tolerated increased dietary protein and needed less nitrogen scavenger medication.

He also has been able to recover from certain typical childhood illnesses like rhinovirus without ammonia building up in his body. Longer follow-up is needed to fully evaluate the benefits of the therapy.

“While KJ will need to be monitored carefully for the rest of his life, our initial findings are quite promising,” Ahrens-Nicklas said.

CRISPR therapies are moving from proof-of-concept to real-world treatments for a growing list of diseases, with the potential to revolutionize the management of both common and ultra-rare genetic disorders. For example, the technology is being used to treat sickle cell anemia.

[David Altshuler, executive vice president and chief scientific officer at Vertex] oversaw further research and development of the experimental therapy through a plethora of preclinical and clinical studies led by CRISPR Therapeutics and Vertex.

In clinical trials, the therapy eliminated small-vessel blockages, known as vaso-occlusive or sickle cell crises, for virtually all patients.

Today, CASGEVY is approved for use in patients with sickle cell disease in the United States and multiple countries in Europe and the Middle East.

“It’s an amazing gift to have been able to play a role in such a thing,” said Altshuler.

Casgevy, a cure for sickle cell disease (SCD) and transfusion-dependent beta-thalassemia (TDT), has had some amazing results and has been approved in the US for the treatment of TDT.

These approvals come following data from a phase 3 trial in both adults and children with severe SCD or TDT. CRISPR Therapeutics and Vertex have shared data from 17 patients with SCD and 27 patients with TDT: the results are dramatic and durable.

25 of 27 individuals with TDT were no longer transfusion dependent following the treatment, some for longer than three years. The other two patients had significant reductions in transfusion frequency (80%, 96%). 16 of 17 SCD patients are free of the vaso-occlusive crises that characterize the illness following treatment. The other patient has been free of hospitalizations related to vaso-occlusive crises.

There is a wide array of other inheritable and metabolic diseases for which CRISPR technologies are being pursued to provide treatment and cure options. Its use as part of treatments for some forms of cancer is also being explored.

Prayers for KJ that he leads a healthy, normal life. As cute as dire wolf cubs are, babies are cuter.

Donations tax deductible
to the full extent allowed by law.