 Haemophilia A is an x-linked, life threatening bleeding disorder arising from defects in the coagulation factor VIII FVIII gene. Current treatment for haemophilia A, the commonest inherited bleeding disorder prevalence of 1 in 5000 individuals consists of life-long, 2-3Xweek, intravenous injection of clotting factor concentrates, which is demanding, exceedingly expensive not widely available nor curative. In contrast, gene therapy offers the potential of a cure for haemophilia A as illustrated by our first unequivocal success in a related condition, haemophilia B. In that study the investigators showed that a single intravenous administration of a serotype 8 based adeno-associated virus, AAV8 vector encoding the factor IX FIX gene resulted in stable 6 years therapeutic expression of FIX without long-lasting toxicity. The investigators plan to use the same AAV8 platform to evaluate a novel FVIII expression cassette, AAV28-HLP-FVIII-V3, in patient with haemophilia A. Extensive preclinical studies demonstrate that AAV28-HLP-FVIII-V3 leads to long-term, endogenous expression of FVIII in mouse and non-human primate models without toxicity even when fifty-fold higher doses than the proposed starting clinical trial dose were used. Therefore, an open label, Phase III dose escalation study entailing a single systemic administration of AAV28-HLP-FVIII-V3 in adults 18 years of age with severe haemophilia A who have baseline factor FVIII levels of 1 of normal has been designed to establish safety and efficacy of our approach. Dosing will begin at 6x1011 vector genome vgkg progressing sequentially to 2x1012vgkg and ultimately 6x1012vgkg in the absence of toxicity. A minimum of 2 patients will be recruited at each dose with a possibility of expanding the dose cohort to a maximum of 6 patients based on safety and efficacy. The study duration for each patient will be 15 years after vector infusion. 