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    • 4. 发明授权
    • Compositions and methods for modulating expression within smooth muscle cells
    • 调节平滑肌细胞内表达的组成和方法
    • US06825035B1
    • 2004-11-30
    • US09807757
    • 2001-04-17
    • Gary K. OwensChristopher MackRandall Blank
    • Gary K. OwensChristopher MackRandall Blank
    • C12N510
    • A01K67/0275A01K2217/05A01K2217/075A01K2227/105A01K2267/0331A01K2267/0375A61K48/00C07K14/4716C12N15/8509
    • 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 &agr;-A. Specifically provided are expression vectors, host cells and transgenic animals wherein an SM &agr;-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.
    • 本发明涉及在SMC内直接表达的启动子,增强子和其它调控元件,其包含控制SMα-A表达的来自5'调控区和第一内含子的转录活性片段。 具体提供的是表达载体,宿主细胞和转基因动物,其中SMα-A调节区能够控制异源基因的表达,过表达内源性SMC基因或病理过程的抑制剂或敲除特异性 基因被认为对SMC中SM相关疾病很重要。 本发明还涉及使用所述载体,细胞和动物筛选用于激动剂的候选分子和涉及SMC的病症拮抗剂的方法。 本发明还涉及用于调节SMC内化合物表达的组合物和方法,以及筛选调节SMC内的表达的化合物。 还提供了通过筛选测定法鉴定的分子和化合物用于治疗性治疗的方法。