Silencing of csn5 gene expression using interfering rna

Abstract

The present invention provides compositions comprising nucleic acids that target CSN5 gene expression and methods of using such compositions to silence CSN5 gene expression. More particularly, the present invention provides unmodified and chemically modified interfering RNA molecules which silence CSN5 gene expression and methods of use thereof, e.g., for treating cell proliferative disorders such as cancer. The present invention also provides nucleic acid-lipid particles that target CSN5 gene expression comprising an interfering RNA molecule, a cationic lipid, a non-cationic lipid, and optionally a conjugated lipid that inhibits aggregation of particles.

1 . An siRNA molecule comprising a double-stranded region of about 15 to about 60 nucleotides in length, wherein the siRNA molecule is capable of silencing COP9 signalsome subunit 5 (CSN5) gene expression. 
     
     
         2 - 12 . (canceled) 
     
     
         13 . The siRNA molecule of  claim 1 , wherein the siRNA molecule comprises at least one of the sequences set forth in Table 1. 
     
     
         14 . The siRNA molecule of  claim 1 , wherein the siRNA molecule comprises at least one of the sequences set forth in Table 2. 
     
     
         15 . The siRNA molecule of  claim 1 , further comprising a carrier system. 
     
     
         16 . The siRNA molecule of  claim 15 , wherein the carrier system comprises a nucleic acid-lipid particle. 
     
     
         17 . A pharmaceutical composition comprising an siRNA molecule of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         18 . A nucleic acid-lipid particle comprising:
 (a) an siRNA molecule of  claim 1 ;   (b) a cationic lipid; and   (c) a non-cationic lipid.   
     
     
         19 - 31 . (canceled) 
     
     
         32 . The nucleic acid-lipid particle of  claim 18 , further comprising a conjugated lipid that inhibits aggregation of particles. 
     
     
         33 - 41 . (canceled) 
     
     
         42 . A pharmaceutical composition comprising a nucleic acid-lipid particle of  claim 18  and a pharmaceutically acceptable carrier. 
     
     
         43 . A method for introducing an siRNA that silences CSN5 gene expression into a cell, the method comprising:
 contacting the cell with an siRNA molecule of  claim 1 .   
     
     
         44 . (canceled) 
     
     
         45 . (canceled) 
     
     
         46 . (canceled) 
     
     
         47 . A method for the in vivo delivery of an siRNA that silences CSN5 gene expression, the method comprising:
 administering to a mammalian subject an siRNA molecule of  claim 1 .   
     
     
         48 . (canceled) 
     
     
         49 . (canceled) 
     
     
         50 . (canceled) 
     
     
         51 . A method for treating cancer in a mammalian subject in need thereof, the method comprising:
 administering to the mammalian subject a therapeutically effective amount of an siRNA molecule of  claim 1 .   
     
     
         52 . (canceled) 
     
     
         53 . (canceled) 
     
     
         54 . (canceled) 
     
     
         55 . A method for introducing an siRNA that silences CSN5 gene expression into a cell, the method comprising:
 contacting the cell with a nucleic acid-lipid particle of  claim 18 .   
     
     
         56 . A method for the in vivo delivery of an siRNA that silences CSN5 gene expression, the method comprising:
 administering to a mammalian subject a nucleic acid-lipid particle of  claim 18 .   
     
     
         56 . A method for treating cancer in a mammalian subject in need thereof, the method comprising:
 administering to the mammalian subject a therapeutically effective amount of a nucleic acid-lipid particle of  claim 18 .