Prime Medicine has unveiled a preclinical gene editing program targeting alpha-1 antitrypsin deficiency (AATD), demonstrating promising efficacy data that could address a significant unmet medical need for approximately 200,000 patients in the United States and European Union. The biotechnology company announced plans to file an investigational new drug (IND) and/or clinical trial application (CTA) in mid-2026.
Breakthrough Preclinical Results
The company's Prime Editing platform achieved up to 72% precise correction of the SERPINA1 gene in hepatocytes of fully humanized mice. This correction targeted the E342K (Pi*Z) mutation, the most prevalent disease-causing mutation in AATD. Importantly, the gene editing restored over 95% of serum alpha-1 antitrypsin (AAT) to the corrected isoform, with healthy M-AAT protein levels reaching well above 20µM in the serum.
"We are also pleased to share the first in vivo preclinical data for our AATD program," said Keith Gottesdiener, M.D., President and Chief Executive Officer of Prime Medicine. "These data reinforce the potential of Prime Editing to restore the disease-causing mutation back to wild-type and address the underlying pathology of both lung and liver manifestations of AATD, without the risk of bystander edits or detectable off-target edits."
Proprietary Delivery Technology
Prime Medicine's approach leverages the company's universal liver lipid nanoparticle (LNP) containing a GalNAc-targeting ligand (GalNAc-LNP) for liver-specific delivery. In preclinical studies, this delivery system demonstrated increased potency and improved safety profile compared to other LNPs that have entered clinical trials. Studies using unoptimized surrogate Prime Editors in non-human primate models showed greater than 50% editing with an excellent safety profile and no detectable off-target edits.
The program represents the second high-value initiative to emerge from Prime Medicine's liver franchise, following their Wilson's Disease program. "This program exemplifies our strategy of using our proprietary, modular liver LNP to accelerate the development of new Prime Editors," Gottesdiener explained.
Addressing Critical Medical Need
AATD is a progressive genetic disorder caused by mutations in the SERPINA1 gene, leading to decreased levels of circulating AAT protein and toxic mutant protein buildup in the liver. The condition affects both lungs and liver, causing symptoms including shortness of breath, wheezing, chronic cough, jaundice, ascites, and cirrhosis. Currently, no disease-modifying or curative treatments are approved for AATD, and many patients progress to liver failure or severe lung disease, potentially resulting in premature death.
Clinical Development Timeline
Prime Medicine is advancing the AATD program through final stages of lead optimization, with IND/CTA filing expected in mid-2026. The company anticipates clinical data for both AATD and Wilson's Disease programs in 2027, aiming to demonstrate Prime Editing's potential across two major genetic liver diseases.
The Prime Editing platform is designed to make precise genetic corrections while minimizing unwanted DNA modifications, with potential applications across thousands of genetic conditions. The technology's versatility allows it to repair various types of genetic mutations across different tissues, organs, and cell types.
