Full protection against phenobarbital-induced attacks of porphyria in AIP mice injected with therapeutic rAAV2/5 or rAAV2/8 vectors. (a) Porphyrin precursor excretion in 24-hour urine samples before and after an acute attack induced with phenobarbital 3 months after the rAAV injection. (b) PBGD activity measured in the livers of female mice 3 months after the (separate) administration of two different rAAV vector serotypes. (c) Hepatic PBGD activity in male AIP animals obtained 1, 2, and 3 months after the administration of different therapeutic vectors. The Wilcoxon signed-rank test was used for comparison of porphyrin excretion before and after phenobarbital inductions. **P < 0.01 versus baseline values in each group. The nonparametric Mann–Whitney test was used for comparison of hepatic PBGD activity. ALA, δ-aminolevulinic acid; AIP, acute intermittent porphyria; cohpbgd, codon-optimized cDNA of human PBGD protein; Luc, luciferase; rAAV, recombinant adeno-associated virus; PBG, porphobilinogen; URO, uroporphyrin; WT, wild type.