Tissue-specific enhancer active in prostate

Abstract

The invention provides a human prostate-specific transcriptional regulatory sequence, polynucleotide comprising such regulatory regions, toxin gene constructs wherein a toxin gene is expressed under the transcriptional control of a human prostate-specific transcriptional regulatory sequence, and methods for treating prostate disease using such toxin gene constructs.

What is claimed is:  
     
         1 . A nucleic acid comprising a region consisting essentially of a transcriptional unit comprising (1) a human transcriptional regulatory element which initiates transcription in cells that express prostate-specific antigen (“PSA”) and is substantially inactive in cells not expressing PSA; and (2) a DNA sequence other than the sequence encoding PSA under the transcriptional initiation regulatory control of said transcriptional regulatory element.  
     
     
         2 . A nucleic acid according to  claim 1 , wherein said transcriptional regulatory element comprises a sequence encompassed within −5322 and −2851 of FIG. 1.  
     
     
         3 . A nucleic acid according to  claim 2 , wherein said transcriptional regulatory element comprises an androgen response element.  
     
     
         4 . A nucleic acid according to  claim 1 , wherein said transcriptional regulatory element comprises an androgen response element.  
     
     
         5 . A nucleic acid according to  claim 1 , wherein said DNA sequence encodes a protein which inhibits proliferation of a cell in which said protein is expressed.  
     
     
         6 . A nucleic acid according to  claim 5 , wherein said protein is a toxin.  
     
     
         7 . A nucleic acid according to  claim 1 , wherein said DNA sequence encodes a surface membrane protein which initiates an immune response upon expression in a human host.  
     
     
         8 . A nucleic acid according to  claim 1 , wherein said transcriptional regulatory element is encompassed within the region 0 to −5322 of FIG. 1.  
     
     
         9 . A viral vector for transfection of human cells comprising a nucleic acid according to any of  claims 1  to  8 .  
     
     
         10 . A viral vector according to  claim 9 , wherein said viral vector is an adenovirus vector.  
     
     
         11 . A composition for introduction of DNA into a viable human cell comprising a nucleic acid according to  claim 1  in a lipofection complex or liposome.  
     
     
         12 . A method for expressing a protein in human prostate cells expressing PSA, said method comprising: 
 maintaining human prostate cells in a medium for maintaining viability, wherein said prostate cells are characterized by comprising a nucleic acid according to  claim 1  as a result of introduction of said nucleic acid into a human prostate cell.    
     
     
         13 . A method according to  claim 12 , wherein said nucleic acid wherein said transcriptional regulatory element comprises a sequence encompassed within about −5300 and −2800 of FIG. 1.  
     
     
         14 . A method according to  claim 12 , wherein said nucleic acid is joined to a viral vector.  
     
     
         15 . A method according to  claim 14 , wherein said viral vector is an adenovirus vector.  
     
     
         16 . A composition for treatment of prostate hypertophy or prostatic neoplasia, said composition comprising: 
 a sterile physiologically acceptable carrier in which is dispersed a nucleic acid comprising a region consisting essentially of a transcriptional unit comprising (1) a human transcriptional regulatory element which initiates transcription in cells that express prostate-specific antigen (“PSA”) and is substantially inactive in cells not expressing PSA; and (2) a DNA sequence which encodes a protein or an antisense sequence which inhibits proliferation of a cell in which said protein is expressed, under the transcriptional initiation regulatory control of said transcriptional regulatory element.    
     
     
         17 . A composition according to  claim 16 , wherein said nucleic acid is in a lipofection complex or liposome.  
     
     
         18 . A composition according to  claim 16 , wherein said nucleic acid is part of a viral vector.  
     
     
         19 . A DNA of not more than about 10 kbp comprising nucleotides of from 0 to −6000 bp of the human PSA, consisting of at least nucleotides from about −2800 to −5300 and free of codons of PSA.  
     
     
         20 . A DNA according to  claim 19 , wherein said nucleotides from about −2800 to −5300 have the sequence of nucleotides −2800 to −5300 of the sequence of FIG. 1.