Alpha-1 antitrypsin (SERPINA1) (A1AT)

Alpha-1 antitrypsin (A1AT), encoded by the SERPINA1 gene, is a critical serine protease inhibitor primarily synthesized in the liver and secreted into the blood. Its primary physiological role is to protect lung parenchyma from proteolytic damage by neutrophil elastase, an enzyme released during inflammatory responses. In individuals with Alpha-1 Antitrypsin Deficiency (AATD), mutations such as the PiZ allele lead to protein misfolding and low circulating levels, resulting in early-onset emphysema and potential liver cirrhosis due to intracellular protein aggregation. The therapeutic normal A1AT transgene is a gene therapy approach designed to deliver a functional copy of the SERPINA1 gene to a patient's cells, typically using adeno-associated virus (AAV) vectors. This strategy aims to restore sustained, therapeutic levels of the A1AT protein in the plasma and lungs, thereby halting the progression of lung disease and reducing the need for lifelong weekly intravenous protein augmentation therapy.

Other names

Alpha-1-proteinase inhibitorSerpin A1AATAlpha-1-antiproteaseProtease inhibitor 1PI1

The therapeutic transgene provides a functional genetic template for the endogenous production of normal alpha-1 antitrypsin protein, which circulates to the lungs to inhibit neutrophil elastase and prevent proteolytic degradation of alveolar elastin.