NOVEL INTERFERON STIMULATED AND REPRESSED GENES

摘要

Methods and model systems for identifying and characterizing new therapeutic agents, particularly proteins, which mimic the activity of all interferons, Type I interferons, IFN- alpha , IFN- beta , or IFN- gamma . The method comprises administering an interferon selected from the group consisting of IFN- alpha , IFN- beta , IFN- tau , IFN- omega , IFN- gamma , and combinations thereof to cultured cells, administering the candidate agent to a duplicate culture of cells; and measuring the effect of the candidate agent and the interferon on the transcription or translation of one or, preferably, a plurality of the interferon stimulated genes or the interferon repressed genes (hereinafter referred to as "ISGs" and "IRGs", respectively). The model system is an array with gene probes that hybridize with from about 100 to about 5000 ISG and IRG transcripts. Methods for identifying and characterizing new therapeutic agents which block the activity of all interferons, Type I interferons, select Type I interferons, or IFN- gamma are also provided. The method comprises administering an interferon selected from the group consisting of IFN- alpha , IFN- beta , IFN- tau , IFN- omega , IFN- gamma , and combinations thereof to cultured cells, administering the interferon and the candidate agent to a duplicate cell culture; and assaying for changes in the levels of transcription of one or, preferably, a plurality of ISGs and IRGs. A method for monitoring the efficacy of interferon therapy in a patient and a method for determining the sensitivity of a subject to treatment with an interferon are provided. The present invention also relates to a method of identifying new ISGs and IRGs. The method comprises administering interferon to cultured cells for a period of time, measuring the levels of gene transcripts from untreated control cells and in cells treated with the interferon using arrays which comprise probes that are known to hybridize with transcripts of known ISGs and IRGs and with transcripts of genes whose products are not known to be ISGs or IRGs; and comparing the levels of transcripts for each gene in the control and interferon-treated cell cultures.