Codon-optimized hFVIII to induce tolerance and correction.

Abstract

<p>BALB/c-HA and BL/6-129/sv-HA mice were injected with 10¹¹vg/mouse of an AAV8 vector expressing codon-optimized hFVIII. <b>A.</b> Coagulation times (aPTT in sec) and <b>B.</b> HFVIIII activity were measured as a function of time after vector administration. Data are averages ±SD for n = 4/group. Mice were challenged (starting at week 10 after gene transfer) with hFVIII at the same dose and schedule as in previous experiments. Anti-hFVIII formation was measured <b>C.</b> as HFVIIII-specific IgG1 titers, and <b>D.</b> by Bethesda assay. Values in panels C and D are shown for individual animals and as averages ± SD and plotted on the same scale as in Fig. 2 to compare magnitude of responses.</p