Influence of genomic configuration and capsid proteins on transduction efficiency. (A) Plasma hFIX levels at 6 weeks after tail-vein administration of varying doses of ssAAV2/8-HCR-hAAT-FIX (▵, n = 4/dose) and scAAV2/8-LP1-hFIXco (□, n = 4/dose). Results are depicted as average together with the standard error of the mean (error bars are not visible at some time points because of the log scale). (B) Representative results of immunohistochemical staining for hFIX at 7 days and 42 days (middle 2 panels) after tail-vein administration of 1 × 10¹¹ scAAV2/8-LP1-hFIXco compared with naive liver (far-left panel) from a control animal. The far-right panel shows hFIX expression in hepatocytes at 42 days after tail-vein administration of 1 × 10¹¹ ssAAV2/8 vector. Magnification is × 40. (C) Influence of AAV capsid proteins on scAAV-LP1-hFIXco–mediated-hFIX expression. Plasma hFIX levels assessed at 4 weeks after tail-vein administration of 1 × 10¹¹ vg of either scAAV2/8-LP1-hFIXco (n = 4) or scAAV2/5-LP1-hFIXco (n = 4). Results are depicted as the average together with the standard error of the mean.