Methods of identifying compounds that inhibit nonstop degradation of mRNA
OwnerHarry C. Dietz, Pamela A. Frischmeyer +2inventors
InventorsHarry C. Dietz, Pamela A. Frischmeyer, Roy Robert Parker, Ambrosius Theodorus Cornelis Van Hoof
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Abstract
The invention provides screening methods for the identification of compounds that inhibit nonstop degradation of mRNA, including compounds that inhibit the exosome. The invention further provides methods of treatment for genetic disorders caused by premature termination codons.
Claims34
A method of identifying a compound capable of inhibiting nonstop degradation of mRNA comprising:
- a) contacting a cell comprising a reporter gene lacking a termination codon with a test compound;
- b) measuring the level of expression or activity of the polypeptide encoded by the reporter gene;
- and
- c) comparing the level of expression or activity of the polypeptide encoded by the reporter gene to the level of expression or activity of the polypeptide encoded by the reporter gene in control cells;
- wherein a compound that upregulates the expression or activity of the polypeptide encoded by the reporter gene, as compared to the level of expression or activity of the polypeptide encoded by the reporter gene in control cells, is identified as a compound capable of inhibiting nonstop degradation of mRNA.
A method of identifying a compound capable of inhibiting nonstop degradation of mRNA comprising:
- a) contacting a cell comprising a reporter gene that has a premature termination codon with a test compound;
- b) contacting the cell with an agent that induces readthrough of premature termination codons;
- c) measuring the level of expression or activity of the polypeptide encoded by the reporter gene;
- and
- d) comparing the level of expression or activity of the polypeptide encoded by the reporter gene to the level of expression or activity of the polypeptide encoded by the reporter gene in control cells;
- wherein a compound that upregulates the expression or activity of the polypeptide encoded by the reporter gene, as compared to the level of expression or activity of the polypeptide encoded by the reporter gene in control cells, is identified as a compound capable of inhibiting nonstop degradation of mRNA.
A method of treating a genetic disorder in a subject caused by a premature termination codon comprising administering to the subject a therapeutically effective amount of compound that induces readthrough of premature termination codons and a therapeutically effective amount of a compound that inhibits nonstop degradation of mRNA, thereby treating the genetic disorder in the subject.
Dependencies are inferred from the claim text.