Cell-based assays for determining drug action

G - Physics – 01 – N

Patent

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G01N 33/53 (2006.01) G01N 33/567 (2006.01)

Patent

CA 2576406

Compositions and methods are provided for the classification of biologically active agents according to their effect on human biology, through the use of complex, primary human cell-based disease models in scalable assay formats. The systems of the invention utilize the simultaneous activation of multiple signaling pathways to generate and identify patterns of expression of physiologically important cell surface and secreted molecules. Combinations of multiple cell types may be utilized. Systems encompassing multiple cell types not only respond to perturbations of each cell type's intracellular signaling networks, but also to inhibition of pathways of communication between cells. Readout information may be combined in multi-system analysis, where the profiles obtained from multiple systems are combined in order to provide enhanced resolution for agent classification.

L'invention concerne des compositions et des méthodes permettant de classer des agents bioactifs en fonction de leur effet sur les processus biologiques humains, au moyen de modèles pathologiques complexes à base de cellules humaines primaires dans des formats d'essai variables. Les systèmes selon l'invention utilisent l'activation simultanée de multiples voies de signalisation afin de générer et d'identifier des motifs d'expression de molécules de surface et de molécules sécrétées importantes sur le plan physiologique. Des combinaisons de multiples types cellulaires peuvent être utilisées. Les systèmes comprenant de multiples types cellulaires répondent non seulement aux perturbations de réseaux de signalisation intracellulaire de chaque type cellulaire, mais encore à l'inhibition de voies de communication entre cellules. Des informations de lecture peuvent être combinées dans une analyse multisystème, dans laquelle les profils obtenus de multiples systèmes sont combinés afin d'obtenir une meilleure résolution pour la classification d'agents.

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