Key Inclusion Criteria: * Capable of providing informed consent * Alpha1AT genotype of ZZ or Z Null * Males and females 18 years and older * Ongoing treatment with A1AT augmentation is not required, however any subject receiving A1AT augmentation therapy must be willing to washout. Washout is defined as at least 8 weeks between last augmentation therapy and pre-treatment plasma A1AT level * Willing to remain off PAT for at least 3 months following treatment * Body mass index 18 to 35 kg/m2 * Fertile men and women of childbearing potential must agree to use barrier contraception for 3 months after treatment Key Exclusion Criteria: * FEV1 \<35 percent of predicted value at the Screening visit * Receiving systemic corticosteroids or other immunosuppressive medications * Immunodeficiency disease or evidence of active infection of any type, including human immunodeficiency virus * Abnormal liver function tests * Organ transplant recipient or awaiting transplantation * Participation in another current or previous gene transfer study * AAVrh.10 neutralizing antibody titer ≥ 1:5 * Female who is pregnant or lactating * History of alcohol or drug abuse within the past 5 years * Any history of allergies that may prohibit study-specific investigations * Receiving an investigational medicinal product or participating in another investigational study within 3 months prior to consent * Cigarette smoking, or any other tobacco use, e-cigarettes or other recreational inhalant within 1 year of the Screening Visit