Efficacy of AAV-mediated gene transfer of rat FVIIa in hemostatically normal rats. (A) AAV8 vector used for infusion in hemostatically normal and HA rats. Inverted terminal repeats (ITRs) flank the expression cassette consisting of a human α1 antitrypsin (hAAT)/apolipoprotein E (ApoE) promoter/enhancer, a synthetic intron, the rat FVIIa cDNA, and a polyadenylation signal (pA). (B) Transgene expression (ng/mL) from AAV-rat FVIIa infusion (4.6 E13 [●, high dose] or 4.6 E11 vg/kg [▪, low dose]; n = 8 per dose) in hemostatically normal animals (baseline subtracted). (C) A PT clotting time assay before and after AAV infusion in hemostatically normal animals. Arrow indicates time of AAV administration. ****P < .0001 vs low dose 4.6 E11 vg/kg, using a repeated measures 2-way analysis of variance (ANOVA) with Bonferroni’s multiple comparison test. Data in panels B-C are presented as mean ± SD.