Design of HC-Ad vectors.

(A-B) The Ad-AAT-cFVIII and Ad-AAT-hFVIII vectors carry the human α1-antitrypsin promoter (AAT) to direct the expression of the canine or human B-domain–deleted FVIII cDNA, respectively. AnHPRT stuffer fragment was used to optimize vector size and to avoid vector rearrangements. (C) In the Ad-Apo-cFVIII vector, the B-domain–deleted FVIII cDNA was expressed from the hepatocyte-specific chimeric ApoE/ApoCII promoter (Apo). An additional stuffer sequence derived from the C346cosmid fragment was used in the Ad-Apo-cFVIII vector.