Transduction in rhesus macaques following liver-targeted delivery of scAAV2/8 and scAAV2/5-LP1-hFIXco. (A) Human FIX concentration in rhesus plasma was determined at the indicated time points after administration of 1 × 10¹² vg/kg (M1-sc [□], M2-sc [○]) scAAV2/8-LP1-hFIXco into the mesenteric vein of 2 rhesus macaques. Treatment of M1-sc with rituximab (Rit × 2 doses) and oral cyclosporine (CyA) is shown. (B) Graphic representation of the reactivity profile of the anti-hFIX antibody in M1-sc, as determined using a panel of hFIX/X chimeras with domain or surface loop substitutions derived from FX. Antibody binding to chimeras was expressed as percentage of binding to wild-type FIX. (C) Transgene expression after mesenteric-vein administration of 4 × 10¹¹ vg/kg scAAV2/8-LP1-hFIXco in 2 macaques (M3-sc [⋄] and M4-sc [▿]). M4-sc additionally received 1 × 10¹² vg/kg scAAV2/5-LP1-hFIXco at 56 days after initial exposure to scAAV2/8. Each sample was independently evaluated on at least 3 separate occasions, and the results are depicted as an average together with the standard error of the mean.