Abstract: Disclosed is a liver specific expression vector designed for expression of blood coagulation factor proteins. The expression vector comprises a DNA coding sequence for a blood coagulation factor operably linked to a liver-specific promoter and a liver-specific enhancer, wherein the promoter and enhancer are derived from different genes. In a particular embodiment, the liver-specific promoter is the human thyroid binding globulin promoter and the liver-specific enhancer is the alpha-1 microglobulin/bikunin enhancer. The expression vector may further contain modifications for optimal liver-specific expression.

Abstract: Novel genes and vectors exhibiting increased expression and novel splicing patterns are disclosed. The gene can comprise one or more consensus or near consensus splice sites which have been corrected. The gene can alternatively or additionally comprise one or more introns within coding or noncoding sequences. The gene can still further comprise modified 5′ and/or 3′ untranslated regions optimized to provide high levels and duration of tissue-specific expression. In one embodiment, the gene comprises the coding region of a full-length Factor VIII gene modified by adding an intron within the portion of the gene encoding the &bgr;-domain, so that the gene is expressed as a &bgr;-domain deleted Factor VIII protein. The novel Factor VIII gene can also be modified to correct one or more consensus or near consensus splice sites within or outside of the coding region.