Antisense oligonucleotide modulation of raf gene expression

Abstract

Oligonucleotides are provided which are targeted to nucleic acids encoding human raf and capable of inhibiting raf expression. The oligonucleotides may have chemical modifications at one or more positions and may be chimeric oligonucleotides. Methods of inhibiting the expression of human raf using oligonucleotides of the invention are also provided. The present invention further comprises methods of inhibiting hyperproliferation of cells and methods of treating or preventing conditions, including hyperproliferative conditions, associated with raf expression.

1 . A method of preventing or treating tumor metastasis in an animal, comprising administering to said animal an oligonucleotide 8 to 50 nucleotides in length which is targeted to mRNA encoding human raf and which is capable of inhibiting raf expression. 
     
     
         2 . The method of  claim 1  which is targeted to mRNA encoding human A-raf. 
     
     
         3 . The method of  claim 1  which is targeted to mRNA encoding human B-raf. 
     
     
         4 . The method of  claim 1  which is targeted to mRNA encoding human c-raf. 
     
     
         5 . The method of  claim 4  which is targeted to a translation initiation site, 3′ untranslated region or 5′ untranslated region of mRNA encoding human c-raf. 
     
     
         6 . The method of  claim 1  which has at least one phosphorothioate linkage. 
     
     
         7 . The method of  claim 1  wherein at least one of the nucleotide units of the oligonucleotide is modified at the 2′ position of the sugar moiety. 
     
     
         8 . The method of  claim 7  wherein said modification at the 2′ position of the sugar moiety is a 2′-O-alkyl, a 2′-β-alkyl-O-alkyl or a 2′-fluoro modification. 
     
     
         9 . The method of  claim 1 , wherein said oligonucleotide is a chimeric oligonucleotide. 
     
     
         10 . The method of  claim 1 , wherein said metastasis is a liver metastasis.