Methods for identifying and validating potential drug targets
OwnerTsvika Greener, Avishai Levy +3inventors
InventorsTsvika Greener, Avishai Levy, Yuval Reiss, Danny Ben-Avraham, Iris Alroy
Life of this patent
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Abstract
This application provides methods for identifying and validating potential drug targets. In one aspect, the application provides a systematic method of creating a database of related protein or nucleic acid sequences with annotations of the potential disease associations of the sequences; and a method for testing the potential disease associations by means of a biological assay and validating the disease association by either decreasing expression of the sequence of interest or increasing expression of the sequence of interest.
Claims78
A method of identifying a potential drug target, comprising:
- providing a database comprising nucleic acid or protein sequences, wherein said sequences are annotated with potential disease-associations of said sequences;
- providing an assay for measuring the disease characteristic of a disease potentially associated to any one of said sequences;
- decreasing expression or activity of at least one of the nucleic acid or protein sequences provided in the database;
- and
- determining whether the decreased expression or activity results in a change in said assay wherein a change in said assay is indicative that said nucleic acid or protein sequence is a potential drug target for the associated disease.
A method of identifying a potential drug target comprising:
- providing a database comprising nucleic acid or protein sequences, wherein said sequences are annotated with potential disease-associations of said sequences;
- providing an assay for measuring the disease characteristic of a disease potentially associated to any one of said sequences;
- increasing expression or activity of at least one of the nucleic acid or protein sequences provided in the database;
- and
- determining whether the increased expression or activity results in a change in said assay wherein a change in said assay is indicative that said nucleic acid or protein sequence is a potential drug target for the associated disease.
A method of identifying a potential drug target comprising:
- providing a database comprising nucleic acid or protein sequences, wherein said sequences are annotated with potential disease-associations of said sequences;
- determining differential expression or activity of said nucleic acid or protein sequences in a cell exhibiting a disease characteristic of a potential associated disease and a corresponding normal cell;
- decreasing expression or activity of said nucleic acid or protein sequences;
- and
- determining the effect of decreased expression or activity on said cell exhibiting disease characteristics of the associated disease, wherein a change in said disease characteristics is indicative that said nucleic acid or protein sequence is a potential drug target for said associated disease.
A method of identifying a potential drug target comprising:
- providing a database comprising nucleic acid or protein sequences, wherein said sequences are annotated with potential disease-associations of said sequences;
- determining differential expression of said nucleic acid or protein sequences in a cell exhibiting disease characteristics of a potential associated disease and a corresponding normal cell;
- increasing expression or activity of said nucleic acid or protein sequence;
- and
- determining the effect of increased expression or activity on said cell exhibiting disease characteristics of the associated disease, wherein a change in said disease characteristics is indicative that said nucleic acid or protein sequence is a potential drug target for said associated disease.
A method for determining whether a test sequence is a potential drug target, comprising:
- providing a database comprising nucleic acid or protein sequences, wherein said sequences are annotated with potential disease-associations of said sequences;
- comparing said test sequence to the sequences provided in said database and predicting potential disease associations;
- validating the predicted disease association by decreasing the activity of said nucleic acid or protein sequences;
- and
- updating the database to include the test sequence and associated annotations.
A method of identifying a therapeutic ribozyme for treating viral infections comprising:
- (a) providing an E3 drug target for treating viral infections;
- (b) administering a ribozyme to decrease expression of said E3 in an infected cell;
- (c) determining the release of virus like particles from said infected cell;
- and
- wherein a decrease in the release of virus like particles is indicative that said ribozyme is a therapeutic ribozyme for treating said viral infections.
A method of identifying a therapeutic ribozyme for treating cancer comprising:
- (a) providing an E3 drug target for treating cancer;
- (b) administering a ribozyme to decrease expression of said E3 in a tumor cell;
- (c) determining the rate of proliferation of said tumor cell;
- wherein a decrease in the rate of proliferation is indicative that said ribozyme is a therapeutic ribozyme for treating said proliferative diseases.
A method of identifying a therapeutic RNAi construct for treating cancer comprising:
- (a) providing an E3 drug target for treating cancer;
- (b) administering a RNAi construct to decrease expression of said E3 in a tumor cell;
- (c) determining the rate of proliferation of said tumor cell;
- wherein a decrease in the rate of proliferation is indicative that said RNAi construct is a therapeutic ribozyme for treating said proliferative diseases.
A method of identifying a therapeutic RNAi construct for treating viral infections comprising:
- (a) providing an E3 drug target for treating viral infections;
- (b) administering a RNAi construct to decrease expression of said E3 in an infected cell;
- (c) determining the release of virus like particles from said infected cell;
- and
- wherein a decrease in the release of virus like particles is indicative that said RNAi construct is a therapeutic RNAi construct for treating said viral infections.
A method of screening E3 proteins as potential drug targets, comprising:
- selecting an E3 protein;
- decreasing expression or activity of said E3 protein in an viral-infected cell;
- determining the release of virus like particles upon decreasing the expression or activity of said E3;
- wherein a decrease the release of the virus like particles is indicative that said E3 protein is a potential drug target.
A method of creating a database of E3 proteins or nucleic acids, comprising:
- receiving a first set of information corresponding to a protein or nucleic acid;
- receiving a second set of information identifying a characteristic of said nucleic acid or protein sequence;
- and
- conducting a clustering analysis to determine how said protein or nucleic acid sequences should be clustered based on the first and second sets of information.
A method of creating a database of proteins or nucleic acid sequences containing the RING domain, comprising:
- receiving a first set of information corresponding to a protein or nucleic acid;
- receiving a second set of information identifying a characteristic of said nucleic acid or protein sequence;
- and
- conducting a clustering analysis to determine how said protein or nucleic acid sequences should be clustered based on the first and second sets of information.
A method of screening an E3 protein as potential drug target, comprising:
- selecting an E3 protein;
- decreasing expression or activity of said E3 protein in a tumor cell;
- determining the rate of proliferation of said tumor cell upon decreasing the expression or activity of said E3;
- wherein a decrease in the rate of proliferation is indicative that said E3 protein is a potential drug target.
A method of screening an E3 protein as a potential drug targets, comprising:
- selecting an E3 protein;
- decreasing expression or activity of said E3 protein in a diseased cell;
- determining the effect of decreasing the expression or activity of said E3 on a Ubiquitin-mediated disorder;
- wherein a change is indicative that said E3 protein is a potential drug target.
A method of identifying a potential drug target for an associated disease comprising:
- (a) conducting a structure-function analysis to determine domain information and/or structural information involved in disease associations;
- (b) providing a database comprising nucleic acid or protein sequence;
- (c) selecting sequences containing the domains and/or structural information relevant to disease associations;
- (d) providing an assay for measuring the disease characteristic;
- (e) decreasing the expression or activity of the nucleic acid or protein sequence selected in step (c);
- and
- (f) determining whether the decreased expression or activity results in change in said assay;
- wherein a change in the disease characteristic is indicative of a potential drug target.
A method of identifying a potential drug target for an associated disease comprising:
- (a) conducting a structure-function analysis to determine domain information and/or structural information involved in disease associations;
- (b) providing a database comprising nucleic acid or protein sequence;
- (c) selecting sequences containing the domains and/or structural information relevant to disease associations;
- (d) providing an assay for measuring the disease characteristic;
- (e) increasing the expression or activity of the nucleic acid or protein sequence selected in step (c);
- and
- (f) determining whether the increased expression or activity results in change in said assay;
- wherein a change in the disease characteristic is indicative of a potential drug target.
Dependencies are inferred from the claim text.