Alpha-1 antitrypsin messenger RNA (AAT mRNA)

Alpha-1 antitrypsin messenger RNA (AAT mRNA) is the transcript of the SERPINA1 gene, which encodes the alpha-1 antitrypsin protein, a member of the serpin superfamily (Source: UniProt P01009). This protein is primarily synthesized in the liver and acts as a critical inhibitor of neutrophil elastase, protecting lung tissue from proteolytic damage (Source: American Thoracic Society). In Alpha-1 antitrypsin deficiency (AATD), mutations such as the PiZ allele result in an mRNA that produces a misfolded protein; this protein polymerizes and accumulates in the liver, causing cirrhosis and hepatocellular carcinoma (Source: NIH StatPearls). Therapeutic strategies targeting AAT mRNA include RNA interference (siRNA) to degrade the mutant transcript and reduce toxic protein accumulation, such as Fazirsiran (Source: N Engl J Med 2022). Additionally, mRNA replacement therapies like mRNA-0639 are being developed to provide a template for functional AAT protein synthesis (Source: Moderna). These approaches aim to address the dual pathology of liver disease and lung destruction associated with AATD by either silencing toxic gain-of-function or restoring loss-of-function.

Other names

SERPINA1 mRNAAlpha-1-proteinase inhibitor mRNAA1AT mRNAAlpha-1 antitrypsin transcript

RNA interference (siRNA) mediated degradation of mRNA to reduce production of mutant Z-AAT protein; or mRNA replacement therapy to restore functional AAT protein levels.