Assay for identifying compounds which affect stability of mrna

Details Assay for identifying compounds which affect stability of mrna Assay for identifying compounds which affect stability of mrna

C - Chemistry, Metallurgy

12

N

C12N 15/85 (2006.01) A61K 35/00 (2006.01) C12N 5/10 (2006.01) C12Q 1/68 (2006.01)

Patent

CA 2356621

A method is provided for the identification of a compound which affects mRNA stability, in particular induces mRNA degradation, in which a DNA expression system which in the absence of test compound is capable of expressing a protein having a detectable signal, wherein the mRNA which codes for the protein and which is transcribed from the expression system comprises at least one copy of a mRNA instability sequence, is contacted with a test compound and the detectable signal is measured in the presence of the test compound and compared with a control. The method may be used to identify compounds which induce degradation of mRNA, e.g. cytokine (e.g. IL-1.beta.) mRNA, which when inappropriately stabilised can give rise to diseases or medical conditions, e.g. cytokine induced inflammatory disease.

L'invention concerne une technique permettant d'identifier un composé qui affecte la stabilité de l'ARNm, notamment par induction de la dégradation de l'ARNm, dans laquelle un système d'expression de l'ADN peut, en l'absence d'un composé d'essai, exprimer une protéine qui possède un signal détectable. L'ARNm codant pour la protéine et transcrit à partir dudit système d'expression, comprend au moins une copie d'une séquence d'instabilité de l'ARNm, est mis en contact avec un composé d'essai, et le signal détectable est mesuré en présence dudit composé d'essai, et comparé à une référence. On peut utiliser cette technique pour identifier des composés induisant la dégradation de l'ARNm, par exemple l'ARNm d'une cytokine (par exemple IL-1.beta.), qui lorsqu'elle est stabilisée de manière anormale peut induire des maladies ou des troubles, par exemple une maladie inflammatoire induite par la cytokine.

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