| 摘要 |
<p>The present invention provides for a regulated gene expression system for growth hormone releasing hormone ('GHRH') characterized by low basal expression and high specific inducibility. The inducible-expression system includes two expression cassettes. The first expression cassette includes a promoter driving the expression of a molecular switch fusion protein which comprises a DNA binding domain, a transactivation domain and a ligand-binding domain. The fusion protein is characterized by an inability to autodimerize in the absence of an inducer. The second expression cassette includes the gene encoding GHRH controlled by an inducible promoter which is activated by the fusion protein dimerizing in the presence of the inducer and binding to the promoter. The present invention includes therapeutic methods for treating growth hormone-related deficiencies associated with the growth hormone pathway; growth hormone-related deficiencies associated with genetic disease; wasting symptoms associated with burn, trauma, cancer, AIDS, and bone loss, as in elderly, or post-fracture. By administering an exogenously supplied inducer the expression system can be activated and controlled.</p> |
