Raf protein kinase therapeutics

Abstract

It is a general object of this invention to provide a DNA segment comprising a Raf gene in an antisense orientation downstream of a promoter. It is a specific object of this invention to provide a method of inhibiting Raf expression comprising expressing an antisense Raf gene in a cell such that said Raf expression is inhibited. It is a further object of the invention to provide a method of inhibiting Raf kinase activity comprising replacement of a serine or threonine amino acid within the Raf gene for a non-phosphorylated amino acid.

What is claimed is:  
     
         1 . A construct comprising a DNA segment comprising a Raf gene in an antisense orientation downstream of a promoter.  
     
     
         2 . The construct according to  claim 1  wherein said Raf gene is Raf-1.  
     
     
         3 . A method of inhibiting Raf expression comprising expressing an antisense Raf gene in a cell under conditions such that said Raf expression is inhibited.  
     
     
         4 . The method according to  claim 3 , wherein said Raf gene is Raf-1.  
     
     
         5 . A method of inhibiting Raf kinase activity comprising: 
 replacing a codon within the Raf gene encoding a serine or threonine amino acid for a codon encoding an amino acid not suceptable to phosphorylation and    transforming said gene into a cell such that said Raf activity is inhibited.    
     
     
         6 . The method according to  claim 5 , wherein said amino acid not suceptable to phosphorylation is alanine.  
     
     
         7 . A method of inhibiting Raf kinase activity comprising: 
 modifying Raf by replacing a serine or threonine amino acid within Raf for an amino acid not suceptable to phosphorylation and    delivering said modified Raf to a cell such that said Raf expression is inhibited.    
     
     
         8 . The method according to  claim 7 , wherein said amino acid not suceptable to phosphorylation is alanine.