Baby becomes pioneer in personalized gene editing treatment for rare disorder

A baby born with a rare and life-threatening genetic disorder is now growing and thriving after receiving a groundbreaking, experimental gene editing therapy tailored specifically for him.

US scientists detailed the case in a newly published study, calling it one of the first successful uses of a personalized gene-editing approach. The technology was used to repair a small but deadly flaw in the baby’s DNA—one that typically causes half of affected infants to die. While widespread use of such treatments remains far off, an article published by CNN captures the doctors' hope that this innovation could eventually benefit millions who’ve been overlooked by advances in genetic medicine due to the rarity of their conditions.

“This marks a crucial first step toward applying gene editing therapies to a broad range of rare genetic diseases that currently lack effective medical options,” said Dr. Kiran Musunuru, a gene editing expert at the US University of Pennsylvania and co-author of the study published in the New England Journal of Medicine. The child, KJ Muldoon of Clifton Heights, Pennsylvania, is among the estimated 350 million people globally affected by rare diseases, the vast majority of which have genetic origins. 

Diagnosed soon after birth with severe CPS1 deficiency—a condition believed to affect about one in a million newborns—KJ’s body couldn’t produce an essential enzyme that helps eliminate ammonia. Without it, ammonia builds up in the bloodstream and becomes toxic. Some patients are eligible for liver transplants as a treatment. In just six months, scientists at Children’s Hospital of Philadelphia and Penn Medicine, working with collaborators, engineered a gene therapy specifically to fix KJ’s defective gene. 

They turned to CRISPR, the gene editing tool that earned its creators the Nobel Prize in 2020. But instead of the original CRISPR method, which slices DNA strands, they used a technique called “base editing,” which swaps a single incorrect DNA base for the correct one—minimizing the chance of unwanted mutations. In February, KJ was given his first intravenous dose of the gene editing therapy, delivered via lipid nanoparticles—microscopic fat droplets that travel to and are absorbed by the liver’s cells. 

Researchers believe the insights gained from KJ’s treatment could pave the way for future therapies for other rare diseases. Because gene therapies are often costly to produce, they tend to focus on more prevalent conditions for economic reasons: a larger patient base increases the likelihood of recouping development costs and earning a profit. The first CRISPR therapy approved by the US Food and Drug Administration, for instance, treats sickle cell disease—a painful, inherited blood disorder affecting millions. 

However, Musunuru noted that their project—partially funded by the National Institutes of Health—demonstrates that developing custom gene therapies doesn’t have to be financially unfeasible. He estimated the cost was comparable to, and possibly less than, the $800,000 or more typically spent on a liver transplant and related care. 

“As we refine the process and shorten development times further, we’ll start seeing economies of scale,” Musunuru said. “That should help bring down the overall cost.” 

By Nazrin Sadigova