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    • 8. 发明申请
    • Context Specific Genetic Screen Platform to Aid in Gene Discovery and Target Validation
    • 背景特异性基因筛选平台,用于基因发现和目标验证
    • US20130040853A1
    • 2013-02-14
    • US13521882
    • 2011-01-21
    • Lynda ChinTimothy P. HeffernanRonald A. DePinho
    • Lynda ChinTimothy P. HeffernanRonald A. DePinho
    • C40B30/06
    • C12N15/1079
    • The present invention relates to a context-specific forward genetic screen designed to systematically assign relative weight of biological evidence to a library of high-probability driver genetic elements in a genetically defined cancer-sensitized model system whose constellation of engineered mutations reflects a particular clinically relevant genetic subclass of a given tumor type. The screen may be formed in vivo or ex vivo. The screen allows for the formulation of clinical path hypotheses for targeting driver genetic elements and, in parallel, the rapid functional validation of the role of the driver genetic element(s) in the cancer. In this manner, the context-specific genetic screen can systematically assign the biological relevance of a library of genetic elements to a clinically-definable genetic and disease context, as well as inform combinations of drugs in the clinic such one uses one drug that targets the newly discovered genetic element or its protein and another drug that targets those genetic elements or its associated proteins which have been engineered into the primary cell model.
    • 本发明涉及一种上下文特异性前向遗传屏幕,其设计用于系统地将生物学证据的相对权重分配给遗传定义的癌症致敏模型系统中的高概率驱动因子遗传图谱库,其中所设计突变的星座反映特定的临床相关性 给定肿瘤类型的遗传亚类。 屏幕可以在体内或离体形成。 屏幕允许制定针对驾驶员遗传元件的临床路径假设,并且同时,快速功能验证驾驶员遗传元件在癌症中的作用。 以这种方式,上下文特异性遗传屏幕可以系统地将遗传元件库的生物相关性分配给临床上可定义的遗传和疾病背景,并且通知临床中药物的组合,例如使用一种靶向 新发现的遗传元件或其蛋白质和另一种靶向已被设计成原代细胞模型的遗传元件或其相关蛋白质的药物。