RNAi MEDIATED KNOCKDOWN OF NUMA FOR CANCER THERAPY

Abstract

This invention relates to the use of short interfering nucleic acid molecules (siRNA) to inhibit Nuclear Mitotic Apparatus Protein (NuMA) gene expression and their use in treatment of disease, including cancer.

1 . A siRNA which targets NuMA mRNA of Genbank Accession number NM-006185. 
     
     
         2 . The siRNA of  claim 1  which targets NuMA mRNA at nucleotides 20-40, 578-598, or 905-928 of Genbank Accession Number NM — 006185, and SNPs thereof. 
     
     
         3 . The siRNA of  claim 1 , targeting a sequence selected from the group consisting of SEQ ID NO:1; SEQ ID NO:2; and SEQ ID NO:3. 
     
     
         4 . The siRNA of  claim 1 , wherein at least one strand consists of a nucleotide strand between 19 and 30 nucleotides in length. 
     
     
         5 . The siRNA of  claim 1 , wherein the siRNA has a structure selected from the group consisting of:
 SEQ ID NO: 4 and SEQ ID NO: 5;   SEQ ID NO: 6 and SEQ ID NO: 7;   SEQ ID NO: 8 and SEQ ID NO: 9; and   SEQ ID NO: 10 and SEQ ID NO: 11.   
     
     
         6 . A method of reducing NuMA expression in a target cell by administering the siRNA of  claim 1 . 
     
     
         7 . A method of reducing NuMA expression in a target cell by administering the siRNA of  claim 4 . 
     
     
         8 . A method of treating cancer by administering to a subject in need thereof a siRNA which targets NuMA at nucleotides 20-40, 578-598, or 905-928 of Genbank Accession Number NM — 006185, and SNPs thereof. 
     
     
         9 . The method of  claim 8 , wherein the siRNA targets a sequence selected from the group consisting of SEQ ID NO:1; SEQ ID NO:2; and SEQ ID NO:3. 
     
     
         10 . The method of  claim 8 , wherein the siRNA consists of a nucleotide strand between 19 and 30 nucleotides. 
     
     
         11 . The method of  claim 8 , wherein the siRNA has a structure selected from the group consisting of:
 SEQ ID NO:4 and SEQ ID NO: 5;   SEQ ID NO: 6 and SEQ ID NO: 7;   SEQ ID NO: 8 and SEQ ID NO: 9; and   SEQ ID NO: 10 and SEQ ID NO: 11.   
     
     
         12 . The method of  claim 8 , wherein said cancer is selected from the group consisting of cervical cancer, epidermoid cancer, oral cancer, glioma, leukemia, brain cancer, esophageal cancer, stomach cancer, bladder cancer, pancreatic cancer, cervical cancer, head and neck cancer, ovarian cancer, melanoma, lymphoma, and multidrug resistant cancer 
     
     
         13 . The method of  claim 8 , wherein said cancer is selected from the group consisting of colorectal cancer, breast cancer, lung cancer, and prostrate cancer. 
     
     
         14 . A composition for the treatment of cancer, comprising the siRNA of  claim 1  and a pharmaceutically acceptable excipient. 
     
     
         15 . The composition of  claim 14 , wherein said cancer is selected from the group consisting of cervical cancer, epidermoid cancer, oral cancer, glioma, leukemia, brain cancer, esophageal cancer, stomach cancer, bladder cancer, pancreatic cancer, cervical cancer, head and neck cancer, ovarian cancer, melanoma, lymphoma, and multidrug resistant cancer. 
     
     
         16 . The composition of  claim 14 , wherein said cancer is selected from the group consisting of colorectal cancer, breast cancer, lung cancer, and prostrate cancer. 
     
     
         17 . A method of treating cancer, comprising administration to a subject in need thereof of an siRNA which inhibits NuMA expression. 
     
     
         18 . A composition for treating cancer, comprising an siRNA which inhibits NuMA expression, and a pharmaceutically acceptable excipient.