A cell’s DNA is being edited as by CRISPR gene-therapy. (Illustration by Jill George using images from the National Human Genome Research Institute & the National Institute of Allergy and Infectious Diseases.)

In the Fall of 2024, a baby in Philadelphia was born with a rare genetic disorder that would usually lead to severe mental and developmental delays, and in most cases death. All due to a mutation in a gene, CPS1, that helps the liver break down the ammonia that naturally occurs in the body. Without the ability to break down ammonia, most children with this mutation die within the first week. But doctors and scientists gave this baby, and hopefully many others to follow, a chance at life when they took on the challenge of developing a custom therapy to edit and fix the faulty CPS1 gene.

To do this, scientists developed a technique using an enzyme called CRISPR-Cas9. In 2012, Jennifer Doudna at U.C. Berkeley and Emmanuelle Charpentier, who was then at Umeå University in Sweden, discovered that CRISPR-Cas9 can be targeted to a specific, chosen, location in the genome, and used to edit that location. For this baby, scientists targeted the location in the genome where CPS1 is found, with the goal of correcting the mutation in the baby’s gene. The scientists wrapped the CRISPR-Cas9 enzyme in lipid molecules to protect it from degradation in the blood stream. In other words, it was a tiny little slippery ball of protective fats, surrounding a gene editing machine made specifically for this baby. The idea was that once this technologically advanced little bundle reached the liver, CRISPR-Cas9 would be able to find and recognize the mutation in CPS1, and then fix it.

With the baby kept alive in the hospital through a very strictly controlled food and medicine regimen and constant intensive care monitoring, the doctors raced against time. Astonishingly, they were able to use CRISPR-Cas9 to go from a diagnosis to a completely new custom treatment in only 6 months - remarkable speed for such a development. As soon as the doctors could, they gave the baby the first of what would be three separate infusions of the lipid-wrapped microballs of CRISPR-Cas9. By 9 months, the treatment was working and the baby had near-normal ammonia levels. The baby was cleared to go home with his parents, and the hospital was able to discharge him.

A baby’s life, saved. A family, made whole.

More than 30 million people in the United States have a similarly rare genetic disease. It was thought that most of these would never have a gene-therapy treatment created, due to the high cost of developing each treatment, and low number of patients per disease. However, thanks to decades of federal funding and a group of doctors willing to try, the scientists forged a new path for companies to develop personalized treatments for a fraction of the previous cost. They saved one baby’s life, and opened the door to saving and helping many, many more.