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Methods for identifying functionally related genes and drug targetsMethods for identifying functionally related genes and drug targets description/claimsThe Patent Description & Claims data below is from USPTO Patent Application 20090263790, Methods for identifying functionally related genes and drug targets. Brief Patent Description - Full Patent Description - Patent Application Claims
This application is a continuation of U.S. patent application Ser. No. 10/309,788, filed on Dec. 4, 2002, which is a continuation-in-part of U.S. patent application Ser. No. 09/750,401, filed on Dec. 28, 2000, now issued as U.S. Pat. No. 6,635,422, which claims the benefit of U.S. Provisional Application Ser. No. 60/173,338, filed Dec. 28, 1999, all of which are hereby incorporated by reference in their entirety. This invention was made with government support under grant number R01 CA79907 from the National Institutes of Health. The United States Government has certain rights in this invention The invention provides methods and compositions for identifying and characterizing functionally related gene products that are associated with mRNA-protein (mRNP) complexes and for characterizing cellular gene expression. The invention also provides methods and compositions for identifying and characterizing therapeutic targets and therapeutics. Most genes are regulated by a complex array of interactions, resulting in unique gene expression patterns. Such gene expression patterns vary between different cell types, cells at different developmental stages or differentiation states, and cells exposed to signaling molecules, stress, infection, or other cellular condition or disorder. Efforts to understand the processes that regulate variant gene expression patterns have concentrated on early events in transcription regulation and in events surrounding translation. In contrast, much less attention has been paid to the role of mRNA-protein complexes (mRNP complexes) in post-transcriptional regulatory processes, such as the regulation of stability, localization, and translation efficiency of mRNAs. Still less is known about the post-transcriptional processes that coordinate the expression of functionally related genes (e.g., genes that share or participate in a certain function or pathway), which are often co-localized to particular mRNP complexes and bound to the same RNA binding protein (RBP). Post-transcriptional gene regulation of some mRNAs is mediated by regulatory elements or sequences that reside in both the introns and exons of pre-mRNAs, and the coding and noncoding regions of mature transcripts. One example of such a regulatory element is the AU-rich instability element (ARE) present in the 3′-untranslated regions (UTRs) of early-response gene mRNAs, many of which encode proteins essential for growth and differentiation. RNA binding proteins associated with mRNP complexes bind to AREs in vitro and mediate post-transcriptional mRNA stability and translation in vivo. However, not all mRNAs that bind to an RNA binding protein possess an ARE or other common regulatory element. Moreover, the mechanism(s) by which an RNA binding protein recognizes mRNAs that do not contain an ARE is not known. In vitro binding assays using RNA binding proteins have shown that the mRNAs that are associated with a particular RNA binding protein are often structurally or functionally related. However, these in vitro methods do not reflect the dynamic nature of mRNA association with mRNP complexes in vivo, which changes in response to intra- and inter- cellular signaling events. A need therefore exists for reliable methods for monitoring RNA binding protein-mRNA interactions, as well as the association of mRNAs and proteins with mRNP complexes in vivo. The use of such methods will allow for the characterization of mRNA-protein interactions and their functional implications, will elucidate biological pathways, and will further allow for the identification of therapeutic targets and therapeutics. The invention provides methods and compositions that are used to identify, utilize, and characterize mRNP complexes to identify functionally related gene products that are coordinately expressed and associated with a particular mRNP complex. The gene products associated with a particular mRNP complex are classified into biologically relevant subsets on the basis of structural and/or functional relationships. These gene products, including mRNAs, RNA binding proteins, other mRNP complex-associated proteins, may participate in a particular biological pathway, such as an enzyme pathway, or may participate in other cellular event or pathology, such as tumor growth, apoptosis, differentiation, aging, or cell toxicity, for example. The functionally and structurally related gene products that are identified and quantified create a ribonomic profile for the cell or population of cells. This ribonomic profile provides a snapshot of the flow of genetic information at a given time in the life of the cell or cell population, in a normal or diseased state, or in response to an environmental influence or drug. The ribonomic profile is used as a diagnostic marker for disease or other cellular event and to rapidly identify therapeutic targets and therapeutics that alter the expression of one or more of the mRNP complex-associated gene products. The identified gene products themselves are also used as diagnostic and therapeutic indicators. For example, the invention provides methods for diagnosing a disease or risk of disease, as well as monitoring a disease state, by identifying and monitoring changes in the expression of mRNP complex-associated gene products in a subject\'s cell sample and comparing the gene expression to that of a normal subject or other non-diseased cell sample. For example, the invention is useful for assessing the cell types present in a population of cells, such as in a tumor, biopsy, or body fluid, by comparing the ribonomic profile of a cell sample to signature RNP profiles characteristic of certain cell types. The identification of certain cell types is useful for diagnosing a tumor or other cellular pathology and for indicating a treatment regimen. The invention provides useful methods for identifying a therapeutic target by contacting a cell sample with a test compound, isolating mRNP complexes, and identifying an mRNP complex component whose expression is altered in response to the compound. The therapeutic target may be any component of the RNP complex or a gene or RNA encoding the component. For example, the RNAs isolated from an RNP complex may be used to probe nucleic acid arrays to identify which genes are affected by the test compound. The invention also provides methods for assessing the efficacy of a test compound as a therapeutic. A cell sample is contacted with a test compound and the mRNP complexes of the cell sample are used to prepare a ribonomic profile that demonstrates changes in expression of gene products associated with the mRNP complexes. A difference in the level of expression of the gene products in the treated cell sample compared to the levels in an untreated cell sample is indicative that the test compound is a candidate therapeutic. The invention may also be used to determine the toxicity of a test compound and to identify genes that participate in cell death. Toxicity can be determined by treating a cell sample with different doses of a test compound, as described above. An array containing nucleic acids that encode regulatory molecules, such as transcription factors, is probed using the RNA isolated from a particular RNP complex, in order to identify the transcription factors, RNA binding proteins, or any other transcriptional, post-transcriptional, translational, or post-translational regulator whose expression is altered in the presence of specific toxicants, in order to identify downstream genes affected by changes in these regulators. 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The method comprises identifying a subject suffering from or at risk for developing cancer, obtaining a body fluid sample from the subject, and determining the sequence integrity of circulating DNA in the sample, wherein the circulating DNA is not purified ... 20090280479 - Use of free circulating dna for diagnosis, prognosis, and treatment of cancer funding - A method of detecting circulating DNA in a body fluid. The method comprises identifying a subject suffering from or at risk for developing cancer, obtaining a body fluid sample from the subject, and determining the sequence integrity of circulating DNA in the sample, wherein the circulating DNA is not purified ... ###  How KEYWORD MONITOR works... a FREE service from FreshPatents1. Sign up (takes 30 seconds). 2. Fill in the keywords to be monitored. 3. Each week you receive an email with patent applications related to your keywords. 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