SERPINA1 and pulmonary emphysema: Evidence shows the response of gene therapy depends on multiple factors, e.g., what vector is used, route of therapy administration, duration of therapy, etc. The AAV8-CASI-luc vector, delivered intratracheally (IT), achieved sustained lung transgene expression for at least 52 weeks, but 29% of mice had persistent expression up to 72 weeks, providing therapeutic AAT protein levels, reducing experimental emphysema severity in mice.