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Recombinant betasub2/sub-adrenergic receptor delivery and use in treating airway and vascular diseases

机译:重组β 2 -肾上腺素能受体的递送及其在治疗气道和血管疾病中的用途

摘要

A method of treating a human subject having airway or vascular disease is disclosed that comprises administering to at least one cell type selected from the group consisting of airway epithelial cells, airway smooth muscle cells, blood vessel endothelial cells, and blood vessel smooth muscle cells, a first composition comprising a vector comprising a DNA sequence encoding a beta2AR (p2-adrenergic receptor) or a mutant thereof, operably linked to a promoter that is functional in at least one of said cells said subject, under conditions whereby the DNA sequence encoding the beta2AR is expressed in at least one of the cells; and optionally administering a second composition comprising at least one beta2-adrenergic agonist into the cells of said subject. A further pharmaceutical composition may be administered comprising a hormone or pharmacological agent that induces the promoter to express the beta2AR in at least one of the target cells. Pharmaceutical compositions comprising the vector comprising a DNA sequence encoding a beta2AR or a mutant thereof, operably linked to a promoter that is functional in at least one of the cells of the subject and kits containing these compositions are also disclosed. An in vitro method of expressing the beta2AR gene in mammalian cells and a method of evaluating the effect of pharmacological compounds on the expression of the beta2AR gene is disclosed.
机译:公开了一种治疗患有气道或血管疾病的人类受试者的方法,该方法包括对选自气道上皮细胞,气道平滑肌细胞,血管内皮细胞和血管平滑肌细胞的至少一种细胞类型给药,第一组合物,其包含载体,所述载体包含编码β2AR(p2-肾上腺素能受体)或其突变体的DNA序列,所述DNA序列在可编码所述β2AR(p2-肾上腺素能受体)的DNA序列的条件下可操作地连接至在所述受试者的至少一个所述细胞中起作用的启动子。 beta2AR在至少一种细胞中表达;以及任选地将包含至少一种β2-肾上腺素激动剂的第二组合物施用到所述受试者的细胞中。可以施用包含激素或药理剂的另一种药物组合物,所述激素或药理剂诱导启动子在至少一个靶细胞中表达β2AR。还公开了药物组合物和包含这些组合物的试剂盒,所述药物组合物包括与包含在受试者的至少一种细胞中起作用的启动子可操作地连接的,编码β2AR或其突变体的DNA序列的载体。公开了在哺乳动物细胞中表达β2AR基因的体外方法和评价药理化合物对β2AR基因表达的影响的方法。

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