Vascular endothelial growth factor D (VEGF-D) antibodies and vectors, and methods of use

Abstract

Isolated nucleic acid molecule comprising an antisense nucleic acid sequence which is antisense to a polynucleotide that encodes a VEGF-D polypeptide, vectors and host cells including the same. Also disclosed are methods of inhibiting VEGF-D function or expression in a mammal, for example, in treating cancer, comprising administering to the mammal in need thereof a vector of the present invention.

1 . An isolated nucleic acid molecule comprising an antisense nucleic acid sequence which is antisense to a polynucleotide that encodes a polypeptide comprising a sequence of amino acids of SEQ ID NOs:3, 5,8 or 9.  
     
     
         2 . The nucleic acid molecule according to  claim 1 , wherein the polynucleotide is genomic DNA.  
     
     
         3 . The nucleic acid molecule according to  claim 1 , wherein the polynucleotide is cDNA.  
     
     
         4 . The nucleic acid molecule according to  claim 1 , wherein the polynucleotide comprises a nucleic acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:7, and sequences complimentary to SEQ ID NO:1, SEQ ID NO:4, SEQ ID NO:6, or SEQ ID NO:7.  
     
     
         5 . The nucleic acid molecule according to  claim 4 , wherein the polynucleotide comprises the nucleic acid sequence of SEQ ID NO: 4.  
     
     
         6 . The nucleic acid molecule according to  claim 1 , wherein the polynucleotide encodes polypeptide comprising amino acid residues 64 through 172 of SEQ ID NO:3.  
     
     
         7 . The nucleic acid molecule according to  claim 1 , wherein the polynucleotide encodes VEGF-DΔNΔC.  
     
     
         8 . A vector comprising a nucleic acid molecule according to  claim 1 , operatively linked to an suitable control sequence.  
     
     
         9 . The vector according to  claim 8 , wherein the control sequence is a promoter.  
     
     
         10 . A host cell comprising a vector according to  claim 8 .  
     
     
         11 . A method of inhibiting VEGF-D function or expression in a mammal, comprising administering to the mammal in need thereof a vector according to  claim 8 .  
     
     
         12 . The method according to  claim 11 , wherein the vector is introduced to the mammal via transformation or transfection of target cells expressing VEGF-D.  
     
     
         13 . The method according to  claim 11 , wherein the mammal is human.  
     
     
         14 . The method according to  claim 11 , wherein the polynucleotide is a human DNA.  
     
     
         15 . A method for inhibiting vascular permeability, proliferation of endothelial cells and endothelial cell differentiation in a mammal, the method comprising administering to the mammal in need thereof a vector according to  claim 8 .  
     
     
         16 . The method according to  claim 15 , wherein the vector is introduced to the mammal via transformation or transfection of target cells expressing VEGF-D.  
     
     
         17 . The method according to  claim 15 , wherein the mammal is human.  
     
     
         18 . The method according to  claim 15 , wherein the polynucleotide is a human DNA.  
     
     
         19 . The method according to  claim 15 , wherein the mammal has cancer.