Deficiency of α–1–antitrypsin (AAT) protein is responsible for approximately 3% of all early deaths due to pulmonary disease. Gene therapy has been suggested as a possible treatment, but it has not been clear whether AAT can be delivered at therapeutic levels. Now, Terence Flotte and colleagues at the University of Florida, Gainesville have reported the development of a recombinant adeno–associated virus (rAAV) that is capable of expressing human AAT at therapeutic levels in mice (Proc Natl Acad. Sci. USA 95:14384–14388, 1998). Injection of the rAAV–hAAT virus into the muscles of two different strains of mice resulted in greater than 800 μg hAAT per milliliter of serum. The human AAT protein was expressed at consistently high levels for three months. High serum levels of AAT are crucial to the success of any gene therapy approach for AAT deficiency, as protein replacement therapy requires weekly intravenous infusions to maintain high enough serum levels to combat the onset of pulmonary disease. Scaling up expression to account for the size difference between mice and humans is the next step, says Flotte.