Prime Medicine announced a preclinical program for alpha-1 antitrypsin deficiency (AATD), using its prime editing technology delivered via a proprietary liver-targeted lipid nanoparticle (LNP). Preclinical studies showed up to 72% gene correction in humanized mice, restoring circulating wild-type AAT protein to normal human levels. The company expects to file an IND/CTA by mid-2026.
This development is notable because AATD currently lacks curative treatments. Prime Medicine’s approach addresses the underlying genetic defect, potentially offering a one-time treatment for both lung and liver manifestations of the disease. The high editing efficiency and restoration of normal AAT protein levels in preclinical models suggest this therapy could significantly improve patient outcomes. This is the second liver-directed program for Prime Medicine, leveraging their proprietary LNP technology and building on existing regulatory and manufacturing infrastructure, demonstrating a focused approach to drug development.
Technically, Prime Editing corrects the common E342K (Pi•Z) mutation in the SERPINA1 gene. The company’s GalNAc-targeted LNP has shown promising preclinical safety and efficacy data, including greater than 50% editing in non-human primates with no detectable off-target effects. This specific delivery system offers advantages over other LNPs in terms of potency, safety, and biodistribution. The program is currently in late-stage lead optimization.
This program’s advancement positions Prime Medicine as a contender in the genetic medicine space, specifically for liver diseases. Successful clinical translation of this preclinical data could establish prime editing as a leading gene editing technology and provide a much-needed curative option for AATD patients. The anticipated 2026 IND/CTA filing will be a key milestone to watch.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
