Portal vein and direct liver injection of AAV-hFIX permit some escape from AAV2 neutralization compared with intravenous delivery. SCID mice were reconstituted with IVIG and achieved average AAV2 neutralizing titers as indicated for each group (5-7 mice/group). Mice then received either 5 × 10¹¹ vg/mouse of AAV2-hFIX intravenously (iv) or 1 × 10¹¹ vg/mouse by portal vein (pv) or direct liver (dl) injection. Circulating human FIX levels were measured in mouse plasmas collected at 4 weeks after vector injection and presented as percent of the mean FIX level in the respective non–IVIG-treated group. Error bars indicate SD in each group.