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    • 1. 发明申请
    • A Lac REPRESSOR-HSV VP16 CHIMERIC TRANSCRIPTIONAL ACTIVATOR PROTEIN SYSTEM FUNCTIONING IN TRANSFECTED MAMMALIAN CELLS
    • 转基因哺乳动物细胞中的Lac REPRESSOR-HSV VP16基因转录激活蛋白系统功能
    • WO1991019784A1
    • 1991-12-26
    • PCT/US1991004180
    • 1991-06-12
    • THE TRUSTEES OF PRINCETON UNIVERSITY
    • THE TRUSTEES OF PRINCETON UNIVERSITYBAIM, Steven, B.LABOW, Mark, A.SHENK, Thomas, E.LEVINE, Arnold, J.
    • C12N05/06
    • C12N15/85C07K14/005C12N2710/16622C12N2800/108C12N2830/00C12N2830/002C12N2830/15C12N2830/55C12N2830/60C12N2830/85C12N2840/44
    • The present invention relates to novel chimeric transactivating proteins comprising a functional portion of a DNA binding protein and a functional portion of a transcriptional activator protein. The chimeric transactivating proteins of the invention offer a variety of advantages, including the specific activation of expression of genes engineered to comprise transactivator responsive elements, thereby achieving exceptionally high levels of gene expression. Furthermore, in various embodiments of the invention, the transactivator proteins may be used to increase expression of some genes while repressing the expression of others, thus permitting a greater degree of control of gene expression patterns than other currently available systems. In preferred embodiments of the invention, the function of the chimeric lac repressor-HSVVP16 tansactivator proteins may be induced, for example, by chemical agents such as IPTG or changes in temperature. In a preferred specific embodiment of the invention, the ability to switch transactivator function on and off may be utilized in the context of transgenic animals and to develop cell lines capable of differentiation.
    • 本发明涉及包含DNA结合蛋白的功能部分和转录激活蛋白的功能部分的新型嵌合反式激活蛋白。 本发明的嵌合反式激活蛋白提供多种优点,包括工程改造成包含反式激活因子反应元件的基因的表达的特异性激活,从而获得异常高水平的基因表达。 此外,在本发明的各种实施方案中,反式激活蛋白可用于增加某些基因的表达,同时抑制其他基因的表达,从而允许比其它目前可用的系统更大程度地控制基因表达模式。 在本发明的优选实施方案中,可以例如通过化学试剂例如IPTG或温度变化来诱导嵌合lac阻遏物-HSVVP16灭活蛋白的功能。 在本发明的优选具体实施方案中,可以在转基因动物的上下文中使用切换反式激活因子功能的能力,并开发能够分化的细胞系。