A Baby Receives the First Customized CRISPR Treatment
- N1C Moderator
- 4 days ago
- 2 min read
Alice Park (TIME)
May 15, 2025
Gene therapy has always held enormous promise to correct genetic diseases, but turning that potential into treatments has been challenging.
In a study published May 15 in the New England Journal of Medicine and presented at the American Society of Gene and Cell Therapy, researchers led by teams at Children’s Hospital of Philadelphia and University of Pennsylvania report on the first use of the gene-editing technology CRISPR in a customized therapy designed to treat one patient with a rare disease. CRISPR is already approvedby the U.S. Food and Drug Administration (FDA) to treat sickle-cell anemia and beta thalassemia, in which patients receive the same gene therapy to treat an abnormality in their red blood cells.
In the latest case, the scientists developed a CRISPR treatment for a boy named KJ, who was born with genetic mutations in his liver cells that prevent him from breaking down proteins properly. As a result, ammonia builds up in his body, which can be toxic to the brain, potentially leading to developmental delays. Led by professor of medicine Dr. Kiran Musunuru at University of Pennsylvania, and Dr. Rebecca Ahrens-Nicklas, director of the Gene Therapy for the Inherited Metabolic Disorders Frontier Program at Children’s Hospital of Philadelphia, the scientists designed a CRISPR gene therapy to specifically address one of KJ’s mutations. “This drug was designed and made for KJ, so in reality this drug will probably never be used again,” says Ahrens-Nicklas of the bespoke nature of the therapy.
While the therapy was created for him, the team is hopeful that the process can be made more universal and applied to other genetic mutations, for which they can plug in the appropriate genetic change to correct a disease.
KJ’s treatment also differs in a few important ways from the approved CRISPR gene-editing treatment for sickle-cell anemia and beta thalassemia. That treatment involves removing cells responsible for generating blood cells from a patient, then genetically editing them using CRISPR to turn on a gene that makes fetal hemoglobin, which is normally turned off in adults. Once the blood stem cells are edited, they are then re-infused back into the patient. The idea is that these cells would start to make more copies of themselves and eventually generate enough healthy red blood cells to minimize or even eliminate the painful symptoms that patients experience.
In KJ’s case, CRISPR was moved from the lab into his own body. The work built on research Musunuru has been conducting to fix a genetic mutation in the PCSK9 gene responsible for increasing LDL cholesterol in some people. The mutation prevents their liver from pulling LDL cholesterol from the blood, which increases the risk of heart events for these patients. He and his team have been developing a therapy to not just turn on or turn off a gene using CRISPR, but to correct that gene by switching out one base pair in its DNA sequence, which is faulty, and replacing it with another base pair to restore the gene back to a normal state. In animals and early studies in people, the CRISPR therapy is successfully lowering cholesterol.
