Method of screening test substances for treating or preventing a disease mediated by plasma cells
AssigneeNew York University
InventorsDavid Ron, Marcella Calfon, Heather Harding, Yuhong Zhang
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Abstract
The present invention relates to a method of screening a compound for potential effectiveness in treating or preventing a mammalian disease mediated by plasma cells or a mammalian disease caused by virus infection of mammalian cells. Compounds are tested for their ability to inhibit IRE1-mediated processing of untranslatable XBP-1 mRNA into translatable XBP-1 mRNA. Drugs that are useful in treating or preventing a mammalian disease mediated by plasma cells and a method for detecting XBP-1 activity in living cells are also described.
Claims42
A method of screening a compound for potential effectiveness in treating or preventing a mammalian disease mediated by plasma cells, said method comprising:
- providing a test compound;
- subjecting the test compound to an assay system suitable for evaluating the test compound's ability to inhibit processing of untranslatable XBP-1 mRNA to translatable XBP-1 mRNA;
- and
- identifying test compounds that inhibit processing of untranslatable XBP-1 mRNA to translatable XBP-1 mRNA as having potential effectiveness in treating or preventing a mammalian disease mediated by plasma cells.
A method of screening a compound for potential effectiveness in treating or preventing a mammalian disease caused by virus infection of mammalian cells, said method comprising:
- providing a test compound;
- subjecting the test compound to an assay system suitable for evaluating the test compound's ability to inhibit processing of untranslatable XBP-1 mRNA to translatable XBP-1 mRNA;
- and
- identifying test compounds that inhibit processing of untranslatable XBP-1 mRNA to translatable XBP-1 mRNA as having potential effectiveness in treating or preventing a mammalian disease caused by virus infection of mammalian cells.
A drug useful in treating or preventing a mammalian disease caused by plasma cells comprising:
- a therapeutic compound that inhibits the processing of untranslatable XBP-1 mRNA to translatable XBP-1 mRNA.
A method of detecting the activity of XBP-1 in living cells, said method comprising:
- providing a living cell transfected with an artificial XBP-1/reporter gene, wherein said XBP-1/reporter gene comprises a coding region for untranslatable XBP-1 and a reporter gene, under conditions effective to allow the reporter gene to express a reporter protein or polypeptide product only when the untranslatable XBP-1 is processed into translatable XBP-1;
- contacting the cell with an endoplasmic reticulum stress-inducing agent under conditions to activate processing of untranslatable XBP-1 mRNA to translatable mRNA;
- and
- detecting the presence of the protein or polypeptide product of the reporter gene in the living cells using an assay system, wherein the presence of said protein or polypeptide product indicates activity of XBP-1 in the living cells.
Dependencies are inferred from the claim text.