CFTR gene regulator

Abstract

The invention relates to a novel CFTR gene regulatory element capable of increasing the activity of the CFTR gene promoter, and to nucleic acid constructs comprising the element together with the CFTR gene coding region. The element and constructs containing it are useful in gene therapy for treating cystic fibrosis.

1 . The oligonucleotide GTCACTTAT and complementary oligonucleotides.  
     
     
         2 . The oligonucleotide ACAATGTGATCTT and complementary oligonucleotides.  
     
     
         3 . An oligonucleotide which is one of the following sequences, or a fragment of one of the following sequences including one or both of the underlined sequences; and oligonucleotides complementary thereto:  
       
         
           
                 
                 
                 
               
                     
                 
                   [SEQ ID NO:1] 
                     
                     
                 
                 
                 
               
                   AATCCTAACTCT GTCACTTAT   
                     
                 
                     
                 
                 
                 
                 
               
                   [SEQ ID NO:2] 
                     
                     
                 
                 
                 
               
                   TA ACAATGTGATCTT AGGCAATTTACTT 
                     
                 
                     
                 
                 
                 
                 
               
                   [SEQ ID NO:3] 
                     
                     
                 
                 
                 
               
                   AATCCTAACTCT GTCACTTAT TA ACAATGTGATCTT AGGCAATTTACTT 
                     
                 
                     
                 
             
                
                
               
            
             
                
                
               
            
             
                
               
            
             
                
                
               
            
             
                
               
            
             
                
                
               
            
           
         
       
     
     
         4 . A nucleic acid element containing up to 200 nucleotide residues including the oligonucleotide of any one of  claims 1  to  3  and having at least 70% homology with the sequence shown in FIG. 1C or a fragment thereof.  
     
     
         5 . A nucleic acid element that is capable of controlling expression of the CFTR gene, which nucleic acid element has at least 70% homology with the sequence shown in FIG. 1C or a fragment thereof.  
     
     
         6 . A nucleic acid element that is a functional CFTR gene regulatory sequence, which nucleic acid element includes one or both of the underlined sequences in  claim 3 , which element is not the sequence TGTCACTTATCTTGC.  
     
     
         7 . A nucleic acid element that is a functional CFTR gene regulatory sequence, which nucleic acid element is derived from intron 1 of the CFTR gene, and which is not the sequence TGTCACTTATCTTGC.  
     
     
         8 . A nucleic acid element as claimed in  claim 7 , which nucleic acid element is derived from the 850 bp intron 1 sequence in GenBank/EMBL DataBank under accession number U47863.  
     
     
         9 . A nucleic acid element as claimed in  claim 8 , up to-200 nucleotide residues long.  
     
     
         10 . A nucleic acid construct up to 50 k bp in length comprising the coding sequence of the CFTR gene together with a nucleic acid element according to any one of  claims 4  to  9 .  
     
     
         11 . A nucleic acid construct as claimed in  claim 10 , wherein the nucleic acid element is present between exon 1 and exon 2 of the coding sequence of the CFTR gene.  
     
     
         12 . A nucleic acid construct as claimed in  claim 10  or  claim 11 , wherein a CFTR gene promoter sequence is present.  
     
     
         13 . A vector containing a nucleic acid construct according to any one of  claims 10  to  12 .  
     
     
         14 . A method of preparing an agent for treating cystic fibrosis by gene therapy, which method comprises bringing a nucleic acid construct according to any one of  claims 10  to  12  into a form suitable for administration.  
     
     
         15 . A method of treating by gene therapy a patient suffering from cystic fibrosis, which method comprises administering to the patient a vector according to  claim 13.