Methods of discovering chemicals capable of functioning as gene expression modulators

Abstract

The present invention provides a method of transcriptionally modulating the expression of a gene-of-interest. The method comprises contacting a cell which is capable of expressing the gene with an amount of a molecule effective to transcriptionally modulate expression of the gene and thereby affect the level of the protein encoded by the gene which is expressed by the cell. Molecules useful in the practice of the invention are characterized as follows (a) do not naturally occur in the cell, (b) bind to DNA or RNA or bind to a protein through a domain of such protein which is not a ligand binding domain of a receptor which naturally occurs in the cell. Additionally, this invention provides a method for determining whether a molecule known to be a modulator of protein biosynthesis is capable of transcriptionally modulating expression of a gene-of-interest.

1 - 160 . (canceled)  
     
     
         161 . A method of transcriptionally modulating the expression of a gene of interest in a cell without modulating the expression of other genes in the cell in a way which would cause an adverse effect on a multicellular organism containing the cell, which gene of interest encodes a protein, the expression of which is associated with a defined physiological or pathological effect within the multicellular organism, which comprises contacting a eukaryotic cell which expresses the gene, with a chemical at a concentration effective to specifically transcriptionally modulate expression of the gene and thereby affect the level of the protein encoded by the gene of interest which is expressed by the cell, which chemical: 
 (a) does not naturally occur in the cell,    (b) specifically and directly transcriptionally modulates expression of the gene of interest, and    (c) does not bind to a receptor ligand binding domain, the binding of ligand to which is normally associated with the defined physiological or pathological effect.    
     
     
         162 . The method of  claim 161 , wherein the cell is a cell of the multicellular organism.  
     
     
         163 . The method of claims  161 , wherein the cell is a human cell.  
     
     
         164 . The method of  claim 161 , wherein the gene of interest is a human gene.  
     
     
         165 . The method of  claim 161 , wherein the defined physiological or pathological effect is cancer.  
     
     
         166 . The method of  claim 161 , wherein the defined physiological or pathological effect is diabetes.