TSRA-196

TSRA-196 is an investigational in vivo gene writing therapy being developed as a one-time, durable treatment for alpha-1 antitrypsin deficiency (AATD), an inherited monogenic disease caused primarily by pathogenic variants in the SERPINA1 gene that impair production of functional alpha-1 antitrypsin protein and lead to progressive lung and liver disease.[1][3][5][9][12] The therapy consists of a genome-editing payload formulated in lipid nanoparticles and is designed to precisely correct the SERPINA1 mutation at the hepatocyte genome locus, thereby restoring endogenous production of functional alpha-1 antitrypsin and addressing the root genetic cause of AATD rather than merely augmenting circulating protein levels.[1][3][5][9][12] In preclinical models, TSRA-196 has shown durable, high-fidelity editing of the Serpina1 locus in mice and non-human primates with high liver specificity and no detectable off‑target or germline editing, supporting its advancement into first‑in‑human trials in adults with PiZZ AATD.[1][3][9][12]