First-in-human clinical case published in the Journal of Hepatology demonstrates precise liver-targeted base editing without detectable off-target alterations
Key Highlights:
- First peer-reviewed publication of a successfully treated PiZZ AATD patient with in vivo gene therapy
- High correction efficiency, precise editing, and promising safety profile
- Conversion of homozygous to heterozygous genotype – a major therapeutic achievement
- Potential to treat numerous hereditary liver diseases and rare variants
Hannover, Germany, November 2, 2026 — In a landmark achievement in the field of genetic medicine, researchers have reported the very first published case in a peer-reviewed journal of a successful clinical treatment of a patient with alpha-1 antitrypsin deficiency (PiZZ) using
in vivo gene therapy. The study, titled
"Liver Biopsy Confirms Precise and Efficient Correction of SERPINA1 After in vivo Base Editing in a Patient with Alpha-1 Antitrypsin Deficiency," is published in the
Journal of Hepatology.
Alpha-1 antitrypsin deficiency is a potentially serious disease that affects both the liver and the lungs. While therapeutic options are available for the pulmonary manifestations, liver transplantation remains the only definitive treatment for the liver damage associated with this genetic disorder.
An alpha-1 antitrypsin deficiency patient, treated with a novel
in vivo base editing therapy, showed stable and clinically meaningful levels of functional alpha-1 antitrypsin (AAT) in the blood. Most notably, a liver biopsy revealed high correction efficiency at the lowest planned dose, with no detectable bystander edits or off-target. This is the first published liver biopsy analysis from a patient treated with
in vivo base editing, offering unprecedented insight into the genomic safety and precision of the therapy.
“This is a transformative moment,” said Prof. Dr. Michael Ott, from Hannover Medical School, and Ren Ji Hospital (Shanghai), one of the investigators. “We are now a step closer to offering permanent, minimally invasive therapies to many patients with hereditary liver diseases.”
Dr. Simon Krooss, MD/PhD, from Hannover Medical School, added: “The high correction efficiency and remarkable precision at such a low dose were truly surprising – and highly encouraging for future applications.”
The therapy effectively converted the patient’s homozygous PiZZ genotype into a mosaic of PiMM (fully corrected), PiMZ (partially corrected), and PiZZ (unedited) cells. This shift from a disease-causing homozygous state to a heterozygous one – which is typically not associated with severe disease – holds immense therapeutic potential, as correcting more than 50% of alleles could significantly reduce risks of lung and liver damage.
“The findings open the door to treating a wide range of hereditary liver disorders, including coagulation diseases and lay the foundation for future therapies targeting rare “n=1” variants,” explained Prof. Heiner Wedemeyer, Chair of the Department of Gastroenterology at Hannover Medical School, and one of the co-authors. With rapid advances in non-viral delivery and editing technologies, the approach may soon extend beyond the liver to other organs and even infectious diseases.
This study underscores the importance of liver biopsy as a critical tool for monitoring genomic safety – a practice the team aims to streamline into a broader clinical pipeline.