Time course of FVIII expression in hemophiliac mice. The adenoviral vectors Av1H8101 (4 × 10¹⁰ particles/mouse) or Av3H8101 (6 × 10¹⁰ particles/mouse) were administered via tail vein injection to groups of 4 or 8 exon 17–disrupted hemophiliac mice, respectively. These vector doses yielded equal liver transduction as determined by Southern analysis (data not shown). At the indicated time points, plasma samples were collected and FVIII biological activity was quantitated. (A) Mean plasma levels of biologically active FVIII. (•) Mice that received Av1H8101. (▪) Mice that received Av3H8101. Data are plotted as a mean value and the standard error of the mean at each time point. The dotted line represents the human therapeutic level of FVIII, 50 mU/mL.33 (B) FVIII plasma levels of individual Av3 vector-treated mice. One mouse (▪) died between 34 and 40 weeks.