A 10-month-old boy suffering from a rare genetic disease is recovering after receiving the world's first personalized gene editing therapy. The doctor in charge at the Children's Hospital of Philadelphia noted, "Although it's still in the early stages, the child's condition is improving beyond expectations."
Dr. Rebecca Ahrens-Nicklas and her research team at the Children's Hospital of Philadelphia announced on the 15th (local time) that the CRISPR gene editing therapy developed for a single patient has been successful, as published in the international journal New England Journal of Medicine.
CRISPR gene editing is not an actual pair of scissors, but an enzyme complex that cuts the desired genes. When the guide RNA recognizes and binds to the DNA (deoxyribonucleic acid) portion that needs to be cut, the Cas9 protein binds to the DNA and cuts it.
KJ Meldun, who received gene therapy, has been unable to produce 'carbamoyl phosphate synthetase 1 (CPS-1)', an enzyme essential for protein metabolism, since birth. Without this enzyme, the body cannot eliminate nitrogen waste such as ammonia, which is a product of protein breakdown.
Ammonia causes lethal toxicity to the brain, known as hyperammonemia. Currently, liver transplantation is the only fundamental treatment, but it is reported that half of the infants with severe CPS-1 deficiency die before receiving a liver transplant.
The treatment received by Meldun is based on cutting-edge gene editing technology known as CRISPR gene editing, which is a technique that precisely changes only one of the four bases constituting the DNA—A, T, C, or G—rather than cutting out a portion of the DNA as typical gene editing does. In other words, while existing gene editing scissors cut sentences, base editing changes only individual letters.
After the first dose of gene therapy, Meldun was able to safely consume the recommended proteins for peers, but he still needed medication to manage ammonia levels. Following the second dose, the amount of medication was successfully reduced, and recently he completed the third and final dose. Currently, the medical staff is closely monitoring Meldun's response while gradually reducing medication use.
The therapy was developed in just six months. The research team identified the precise editing location based on Meldun's genetic information, tested it in mouse and monkey models, and received expedited approval from the U.S. Food and Drug Administration (FDA). With active support from corporations and government agencies, the process that typically takes years was completed in half a year.
Experts evaluated that this gene therapy developed for just one individual succeeded in being applied to an actual patient. However, whether ultra-personalized therapies can be applied to more patients remains uncertain. Given that existing gene therapies face commercialization challenges due to high costs, a personalized treatment for just one person presents even greater financial barriers.
New England Journal of Medicine (2025), DOI: https://doi.org/10.1056/NEJMoa2504747