A NOVEL LUCIFERASE REPORTER SYSTEM FOR NON-INVASIVE MONITORING OF NFkB ACTIVITY IN VITRO AND IN VIVO

摘要

The present invention relates to assays, methods and cells to monitor the effect of agents on cell signalling pathways. In particular, the present invention relates to an assay for real-time, non-invasive monitoring of the effect of an agent which modulates (i.e. increases or decreases) a cell signalling pathway which is regulated by transcription factors which bind to transcription response elements (TREs) to regulate gene expression. In particular in some embodiments, the assay comprises a cell which comprises the nucleic acid encoding a secretable luciferase protein, such as Gaussia luciferase which is operatively linked to numerous tandem repeats of transcription response elements (TRE), and where the cell is contacted with an agent and an increase or decrease in the expression of the secretable luciferase identifies an agent which increase or decreases the cell signalling pathway respectively. In some embodiments, the assay is useful for identifying agents which increase or decrease the NF- B pathway. In some embodiments, the assay is useful to identify agents which increase or decrease the NF- B pathway in immune or inflammatory cells.