Methods of inhibiting VEGF-C

Abstract

The present invention provides RNA molecules (e.g., antisense, RNAi, or siRNA) specific for VEGF-C, and further provides methods of reducing expression of VEGF-C in cells (e.g., cancer cells).

1 . An isolated nucleic acid molecule comprising a first portion, wherein the first portion is no more than 30 nucleotides in length, wherein the first portion comprises 5′-AAG ATC TGG AGG AGC AGT TAC-3′ (SEQ ID NO:1), 5′-AAA GGA GGC TGG CAA CAT AAC-3′ (SEQ ID NO:2), 5′-AAC CTC CAT GTT GTG TCC GTC-3′ (SEQ ID NO:3), or 5′-AAG AAG TGT GTC GTT GTG TCC-3′ (SEQ ID NO:5).  
     
     
         2 . The nucleic acid molecule of  claim 1 , further comprising a second portion, wherein the second portion has a sequence that is complementary to the first portion.  
     
     
         3 . The nucleic acid molecule of  claim 2 , further comprising a linking sequence that joins the first portion and the second portion.  
     
     
         4 . The nucleic acid molecule of  claim 3 , wherein the linking sequence forms a loop of a hairpin.  
     
     
         5 . The nucleic acid molecule of  claim 4 , wherein the linking sequence is about 4 to about 10 nucleotides in length.  
     
     
         6 . The nucleic acid molecule of  claim 1 , wherein the first portion is from about 19 to about 23 nucleotides in length.  
     
     
         7 . A vector comprising the nucleic acid molecule of  claim 1 .  
     
     
         8 . A host cell comprising the vector of  claim 7 .  
     
     
         9 . A method of reducing the expression of VEGF-C in a cell, comprising the step of introducing the isolated nucleic acid molecule of  claim 1  or the vector of  claim 7  in to the cell in an amount sufficient to reduce the expression of VEGF-C in the cell.  
     
     
         10 . The method of  claim 9 , wherein expression of VEGF-C is reduced by at least 10%.  
     
     
         11 . The method of  claim 9 , wherein the cell is a cancer cell.  
     
     
         12 . The method of  claim 11 , wherein the cancer cell is an epithelially-derived cancer cell.  
     
     
         13 . The method of  claim 12 , wherein the epithelially-derived cancer cell is a head and neck cancer cell, a breast cancer cell, a colon cancer cell, or a prostate cancer cell.  
     
     
         14 . The method of  claim 11 , wherein the cancer cell is in vivo.  
     
     
         15 . The method of  claim 11 , wherein the cancer cell is in a mammal.  
     
     
         16 . The method of  claim 15 , wherein the mammal is a human.  
     
     
         17 . The method of  claim 11 , wherein proliferation of the cancer cell is inhibited.  
     
     
         18 . A pharmaceutical composition comprising the isolated nucleic acid molecule of  claim 1  or the vector of  claim 7.