Map of AAV human and canine FVIII heavy- and light-chain vectors (AAV-hFVIII-HC, AAV-hFVIII-LC, AAV-cFVIII-HC, and AAV-cFVIII-LC). The regulatory regions in each vector are as follows: ITR indicates AAV inverted terminal repeat; ApoE-HCR, apolipoprotein E hepatic control region, hAAT, human alpha one antitrypsin promoter; intron, CMV-β-globin chimeric intron; hGH PA, human growth hormone poly A. The human heavy chain is composed of the A1 and A2 domains preceded by the FVIII signal sequence, SS. The hFVIII-HC is followed by 5 aa (741-745) of the B-domain. The cFVIII-HC construct is identical except in addition to the regulatory and FVIII elements in the human construct, the cFVIII-HC construct is followed by 89 aa of the upstream B-domain (734-822). The human and canine light chain constructs are preceded by 86 aa of the B-domain, then the A3, C1, and C2 regions.