Importantly and with some relevance to the context of decreasing the immunogenicity of rFVIII for better treatment of hemophilia A patients, we demonstrated that the treatment with the bioengineered rhFVIII-H6A (compared to plasma-derived and recombinant reference products) corrected the hemophilic phenotype in vivo, inducing very low levels of antibody formation and especially low FVIII neutralizing activity. This evidence concerns the gene F8 and hemophilia A.