High throughput functional genomic screening methods for osteoarthritis
OwnerDale Bodian, Sherif Daouti +3inventors
InventorsDale Bodian, Sherif Daouti, Chandrika Kumar, Brian Latario, Joseph Quintavalla
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Abstract
High-throughput functional screening assays are provided that identify genes and gene products that are associated with the pathogenesis of osteoarthritis (OA) in chondrocytes. In addition, genes and gene products identified by such functional assays are also provided. The genes and gene products provided herein are useful inter alia for diagnosing OA in individuals and as drug targets for identifying drugs to treat OA.
Claims48
A method for identifying a nucleic acid associated with osteoarthritis (OA), which method comprises:
- (a) transfecting a cell with a nucleic acid so that the nucleic acid is expressed by the cell;
- and
- (b) detecting expression by the cell of one or more marker nucleic acids, each of said one or more marker nucleic acids being associated with OA
- wherein expression of the one or more marker nucleic acids by the cell identifies the nucleic acid transfected into the cell as a nucleic acid associated with OA.
A method for identifying a nucleic acid associated with osteoarthritis (OA), which method comprises:
- (a) transfecting a cell with a nucleic acid so that the nucleic acid is expressed by the cell;
- and
- (b) detecting expression by the cell of one or more marker polypeptides, each of said one or more marker nucleic acids being associated with OA
- wherein expression of the one or more marker polypeptides by the cell identifies the nucleic acid transfected into the cell as a nucleic acid associated with OA.
A method for identifying a polypeptide associated with osteoarthritis (OA), which method comprises:
- (a) transfecting a cell with a nucleic acid that encodes a polypeptide, so that the polypeptide is expressed by the cell;
- and
- (b) detecting expression by the cell of one or more marker nucleic acids, each of said one or more marker nucleic acids being associated with OA,
- wherein expression of the one or more marker nucleic acids identifies the polypeptide expressed by the nucleic acid transfected into the cell as a polypeptide that is associated with OA.
A method for identifying a polypeptide associated with osteoarthritis (OA), which method comprises:
- (a) transfecting a cell with a nucleic acid that encodes a polypeptide, so that the polypeptide is expressed by the cell;
- and
- (b) detecting expression by the cell of one or more marker polypeptides, each of said one or more marker nucleic acids being associated with OA.
- wherein expression of the one or more marker polypeptides by the cell identifies the polypeptide expressed by the nucleic acid as a polypeptide that is associated with OA.
A method for identifying a nucleic acid associated with osteoarthritis (OA), which method comprises:
- (a) transfecting a chondrocyte cell with a nucleic acid so that the nucleic acid is expressed by the chondrocyte cell;
- and
- (b) detecting proliferation of the chondrocyte cell
- wherein proliferation of the chondrocyte cell indicates that the nucleic acid is associated with OA.
A method for identifying a polypeptide associated with osteoarthritis (OA), which method comprises:
- (a) transfecting a chondrocyte cell with a nucleic acid that encodes a polypeptide, so that the polypeptide is expressed by the chondrocyte cell;
- and
- (b) detecting proliferation of the chondrocyte cell,
- wherein proliferation of the chondrocyte cell identifies the nucleic acid as a nucleic acid associated with OA.
A method for identifying an individual having osteoarthritis (OA), which method comprises:
- (a) detecting a candidate gene or gene product in cartilage or chondrocyte cells from an individual, said candidate gene or gene product being a gene or gene product set forth in Table V or VI;
- and
- (b) comparing the level of said candidate gene or gene product in the individual to levels of the candidate gene or gene product in individuals not having osteoarthritis,
- wherein elevated levels of the candidate gene or gene product in cartilage or chondrocytes derived from the individual indicates that the individual has OA.
A method for identifying a compound that may be used to treat, prevent or ameliorate osteoarthritis (OA), which method comprises:
- (a) contacting a test compound to a cell;
- (b) detecting expression by the cell of a candidate gene or gene product, said candidate gene or gene product being a gene or gene product set forth in Table V or VI;
- and
- (c) comparing the level of the candidate gene or gene product expressed by the cell contacted with the test compound to the level of expression by a cell that is not contacted with the test compound,
- wherein a decreased expression of the candidate gene or gene product by the cell contacted with the test compound indicates that the test compound may be used to treat OA.
A method to treat, prevent or ameliorate OA comprising administering to a subject in need thereof an effective amount of one or more modulators of one or more candidate genes selected from the group consisting of those disclosed in Table V and Table VI.
A method to treat, prevent or ameliorate OA comprising administering to a subject in need thereof a pharmaceutical composition comprising an effective amount of one or more modulators of any one or more candidate genes selected from the group consisting of those disclosed in Table V and Table VI.
A pharmaceutical composition comprising one or more modulators of any one or more candidate genes selected from the group consisting of those disclosed in Table V and Table VI in an amount effective to treat or ameliorate OA in a subject in need thereof.
A method to treat, prevent or ameliorate OA comprising
- (a) assaying a subject for mRNA levels for any one or more candidate genes selected from the group consisting of those disclosed in Table V and Table VI.;
- and
- (b) administering to a subject with increased levels of mRNA compared to controls a modulator of any one or more of said candidate genes in an amount sufficient to treat, prevent or ameliorate OA.
A method to treat, prevent or ameliorate OA comprising:
- (a) assaying a subject for levels of any one or more gene products encoded by a candidate gene selected from the group consisting of those disclosed in Table V and Table VI;
- and,
- (b) administering to a subject with increased levels compared to controls a modulator of any one or more of said gene products in an amount sufficient to treat, prevent or ameliorate OA.
A diagnostic kit for detecting mRNA levels or protein levels of a candidate gene or gene product selected from the group consisting of those disclosed in Table V and Table VI, said kit comprising:
- (a) a polynucleotide of said candidate gene or a fragment thereof;
- (b) a nucleotide sequence complementary to that of (a);
- (c) an expression product of said candidate gene, or a fragment thereof;
- or
- (d) an antibody to said expression product
- wherein components (a), (b), (c) or (d) may comprise a substantial component.
Dependencies are inferred from the claim text.