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AssigneeSetagon, Inc.
InventorsGary K. Owens, Christopher Mack, Randall Blank
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The present invention relates to promoters, enhancers and other regulatory elements that direct expression within SMC, comprising nucleotide sequences from the 5′ regulatory region and the first intron, and transcriptionally active fragments thereof, that control expression of an SM α-A. Specifically provided are expression vectors, host cells and transgenic animals wherein an SM α-A regulatory region is capable of controlling expression of a heterologous gene, over-expressing an endogenous SMC gene or an inhibitor of a pathological process or knocking out expression of a specific gene believed to be important for an SM-related disease in SMC. The invention also relates to methods for using said vectors, cells and animals for screening candidate molecules for agonists and antagonists of disorders involving SMC. The invention further relates to compositions and methods for modulating expression of compounds within SMC, and to screening compounds that modulate expression within SMC. Methods for using the molecules and compounds identified by the screening assays for therapeutic treatments also are provided.
An isolated polynucleotide comprising nucleotides 3331-3656, 3495-3599 or 3421-3548 of SEQ ID NO:
An isolated polynucleotide comprising a smooth muscle (SM) α-A promoter/enhancer in operable association with a heterologous polynucleotide, wherein the promoter/enhancer comprises sufficient sequence from the first intron of the SM α-A gene to confer smooth muscle cell-specific expression in vivo and wherein the promoter/enhancer comprises a nucleic acid that hybridizes to the complement of SEQ ID NO:1 when DNA comprising the complement of SEQ ID NO:1 is hybridized in 0.5 M NaHPO4, 7% sodium dodecyl sulfate (SDS), 1 mM EDTA at 65° C., and washed in 0.1×SSC/0.1% SDS at 68° C.
An isolated genetically-engineered host cell comprising a polynucleotide comprising a SM α-A promoter/enhancer in operable association with a heterologous polynucleotide, wherein the promoter/enhancer comprises sufficient sequence from the first intron of the SM α-A gene to confer smooth muscle cell-specific expression in vivo and wherein the promoter/enhancer comprises a nucleic acid that hybridizes to the complement of SEQ ID NO:1 when DNA comprising the complement of SEQ m NO:1 is hybridized in 0.5 M NaHPO4, 7% sodium dodecyl sulfate (SDS), 1 mM EDTA at 65° C., and washed in 0.1×SSC/0.1% SDS at 68° C.
Dependencies are inferred from the claim text.