The transfection efficacy of several vectors containing the full genomic hAAT gene with its natural promoter (pTG7101) and others containing the cDNA of hAAT gene driven by cytomegalovirus immediate-early promoter or the 0.5 kb upstream of hAAT gene sequence has been studied by hydrodynamic tail-vein injection (20 μg/mouse). pTG7101 (but not the other plasmids) results in therapeutic and stable concentration of hAAT in plasma. A dose–response study with this plasmid (0.3–320 μg/mouse) confirms that hAAT remains long-term stable in plasma, with therapeutic concentrations of hAAT (> 0.9 mg/ml). The parameters of the dose–response curve were: R: 0.98, E max 3449.0±279.7 μg/ml and EC 50 1.2× 10 12 plasmid-gene units. In addition, 4 months after transfection, the intrinsic efficacy of transgenic expression (amount of RNA/DNA) in mouse liver was 50–80% that normally expressed by the mouse gene. The important efficacy of nonviral genomic DNA opens a new avenue in the safety applications of human gene therapy.