Inhibition of viral gene expression using small interfering rna

Abstract

The invention provides methods, compositions, and kits comprising small interfering RNA (shRNA or siRNA) that are useful for inhibition of viral-mediated gene expression. Small interfering RNAs as described herein can be used in methods of treatment of HCV infection. ShRNA and siRNA constructs targetING the internal ribosome entry site (IRES) sequence of HCV are described.

1 . An RNA sequence consisting of
 a. a first RNA sequence, wherein the first RNA sequence is SEQ ID NO:34, (SEQ ID NO:35), (SEQ ID NO:36), (SEQ ID NO:37), (SEQ ID NO:38), (SEQ ID NO:39), (SEQ ID NO:40), (SEQ ID NO:41), (SEQ ID NO:42), (SEQ ID NO:43), (SEQ ID NO:44), (SEQ ID NO:45), (SEQ ID NO:46), (SEQ ID NO:47), (SEQ ID NO:48), (SEQ ID NO:49), (SEQ ID NO:50), (SEQ ID NO:51); (SEQ ID NO:52), (SEQ ID NO:53), (SEQ ID NO:54), (SEQ ID NO:55), (SEQ ID NO:56), or a sequence that differs from a foregoing sequence by one, two, or three nucleotides;   b. a second RNA sequence that is a complement of the first sequence;   c. a loop sequence positioned between the first and second nucleic acid sequence, the loop sequence consisting of 4-10 nucleotides; and   d. optionally, a two nucleotide overhang.   
     
     
         2 .- 17 . (canceled) 
     
     
         18 . A method of inhibiting expression or activity of a hepatitis C virus, the method comprising
 a. providing a cell that can express a hepatitis C virus; and   b. contacting the cell with an RNA sequence of  claim 1 .   
     
     
         19 - 61 . (canceled)