The favorable acute toxicity profile observed, combined with therapeutic-range LV dose-dependent FVIII activity, provide a comfortable therapeutic window and encourage further development of LV-mediated liver gene therapy for hemophilia A. Because of the high immunogenicity of the FVIII protein, anti-human FVIII immune responses are expected in NHP and have been previously observed in pre-clinical studies of both FVIII protein and AAV-vector mediated gene replacement25,29. The gene discussed is F8; the disease is hemophilia A.