One year ago, on May 15, 2025, the New England Journal of Medicine published "Patient-Specific In Vivo Gene Editing to Treat a Rare Genetic Disease." The DOI is 10.1056/NEJMoa2504747. The paper described a customized lipid-nanoparticle-delivered base-editing therapy — named k-abe — designed and administered to a single infant patient, KJ, with severe carbamoyl phosphate synthetase 1 deficiency, a urea-cycle disorder with an estimated 50 per cent mortality in early infancy. The patient received the first infusion at approximately seven months of age and a second infusion three weeks later. In the seven weeks after the initial infusion, the patient tolerated increased dietary protein and a halved dose of his nitrogen-scavenger medication, without serious adverse events. [1]

The Children's Hospital of Philadelphia and Penn Medicine team — led by Rebecca Ahrens-Nicklas, MD, PhD, director of CHOP's Gene Therapy for Inherited Metabolic Disorders Frontier Program, and Kiran Musunuru, MD, PhD, of Penn — accomplished what had not been attempted before: a single-patient designer therapy, manufactured and approved within six months of diagnosis. The case was selected as one of the most notable NEJM papers of 2025. [2]

CHOP marked the one-year anniversary of KJ's first dose on February 24, 2026 — not May 15, but the February treatment date — with a public statement noting that KJ "has achieved meaningful clinical improvements, such as walking and talking," and continues to grow. Ahrens-Nicklas characterised the outcome: "He's able to handle more dietary protein, requires less nitrogen-scavenging medication, and we're seeing better control of ammonia levels during colds and similar childhood illnesses." [3] No formal follow-up dataset has been published. No second peer-reviewed paper has appeared. The May 15 NEJM-publication anniversary closes Thursday on the one-year window for the kind of safety-and-efficacy follow-up data the field needs to gauge durability.

What the field would learn from a one-year follow-up: whether nitrogen-scavenger reduction held, whether ammonia control stayed stable through the childhood illnesses that previously put CPS1-deficient infants at risk of fatal hyperammonemia, and — most importantly — whether base-editing in the liver via lipid nanoparticles produces durable correction or whether re-dosing is required. The platform's promise depends on the durability question. The team has not publicly addressed the follow-up dataset. Ahrens-Nicklas's frontier program continues recruiting candidate patients with similar single-nucleotide variants in urea-cycle disorders. The publication record is what is one year on and quiet.

-- KENJI NAKAMURA, Tokyo