Thursday, 11 June 2026 edition — The Vital Record

Alpha-1 antitrypsin deficiency (AATD), one of the most common serious genetic diseases of the liver and lungs, affects an estimated 100,000 Americans with its most severe form — most of them carrying two copies of the PIZZ allele, a single-nucleotide substitution that causes misfolding and aggregation of the SERPINA1 protein in liver cells. A medRxiv preprint posted this week reports that a single patient in a Phase I/Ia trial received an intravenous infusion of an investigational base editor, YOLT-202, and ten weeks later underwent a liver biopsy. The histological result: 54% on-target correction of the PIZZ allele by Sanger sequencing and 57% by Illumina next-generation sequencing, with no off-target edits detected.

The case report, which has not yet been peer reviewed, is the first published histological evidence that base editing can correct a disease-causing point mutation at therapeutically relevant efficiency in a living human organ.