The baby whose life was saved by the first personalized CRISPR therapy

"To the research team working to save him, KJ Muldoon was first known only as Patient Eta. But within months, KJ's name - and megawatt, chubby-cheeked smile - would be splashed across newspapers and broadcasts around the world as the first known person to receive a personalized CRISPR-based genome-editing therapy. Soon after KJ was born in August 2024, doctors noticed that he was sleeping too much and eating too little."

"When the body breaks down proteins, it produces ammonia - a toxic substance that is usually processed by enzymes in the liver and excreted in urine. CPS1 deficiency compromises one of these enzymes, causing ammonia to accumulate in the blood, which can eventually damage the brain. The condition can be treated with a liver transplant, but about half of all babies with CPS1 deficiency die in early infancy."

"Previous gene-editing therapies were designed to treat many people. The first approved CRISPR therapy, called Casgevy, could potentially treat tens of thousands of people with one of two blood disorders. By contrast, KJ's therapy would work only for him. The team used an offshoot of CRISPR genome editing, called base editing, to target the problematic mutation - one faulty DNA letter out of the three billion in the human genome - and correct it ( K. Musunuru et al. N. Engl. J."

KJ Muldoon was born in August 2024 and presented with excessive sleepiness and poor feeding. Diagnostic testing revealed carbamoyl-phosphate synthetase 1 (CPS1) deficiency, a rare disorder that impairs ammonia processing and can cause brain damage. About half of infants with CPS1 deficiency die in early infancy; liver transplant is a treatment option. A clinical team pursued a personalized genomic approach using CRISPR base editing to correct the single-letter mutation in KJ's liver cells. Earlier CRISPR therapies targeted larger patient populations, while KJ's therapy was uniquely tailored to his DNA sequence.

Read at Nature