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.

Abstract: Antisense constructs ditrected against viral cis-acting post-transcriptional regulatory sequences ("PREs") are disclosed. In one embodiment, the antisense construct is an expression plasmid encoding one or more antisense transcripts which hybridize under intracellular conditions to all or a portion of a viral PRE within a viral transcript, the PRE having the function of directing export of the viral transcript from the nucleus to the cytoplasm of a cell. The antisense constructs can be used to inhibit viral production, such as HBV production.

Abstract: Expression vectors are disclosed comprising intronless genes containing one or more near consensus splice sequences and one or more copies of a viral cis-acting post-transcriptional regulatory element which is transcribed along with the gene and causes export of the gene transcript from the nucleus into the cytoplasm of the cell. In a preferred embodiment, the vectors are targeted for delivery to specific cells in the form of a molecular complex made up of the plasmid releasably linked to a nucleic acid binding agent and a ligand which binds to a component on the surface of a cell. Use of viral cis-acting post-transcriptional regulatory elements as disclosed can increase expression of intronless genes with near-consensus splice sites.