Transient immune suppression to enhance phenotypic correction in HemA mice after IO infusion of G-F8/N6-LV. HemA mice were pretreated with combined drugs (Dex 4 times + anti-CD8α mAb 5 times) and then given an IO infusion of self-inactivating LVs encoding hFVIII variant with the proximal 226–amino acid region of the B domain (F8/N6) under the control of GP1Bα promoter (G-F8/N6-LV; 2.2 × 106 ifu per animal) on day 0. (A) HemA phenotypic correction in mice treated with G-F8/N6-LV or G-F8/N6-LV plus drugs was evaluated by tail clip assay on day 70 (n = 6-8 per group). The average blood loss of untreated HemA mice was set as 100%. Wild-type C57BL/6 mice were used as positive controls. (B) HemA phenotypic correction in mice treated with G-F8/N6-LV plus drugs or G-F8/N6-LV was also evaluated by measuring carotid artery blood flow rate on day 84. (C) Plasma samples were collected from mice treated with G-F8/N6-LV plus drugs or G-F8/N6-LV on day 84. hFVIII activity and anti-FVIII antibodies were measured by activated partial thromboplastin time and Bethesda assays, respectively. Each symbol represented an individual animal. Data were expressed as mean ± standard deviation of the mean.