Nucleic Acid-Mediated Treatment of Diseases or Conditions Related to Levels of Vascular Endothelial Growth Factor Receptor (VEGF-R)

Abstract

The present invention relates to nucleic acid molecules such as ribozymes, DNAzymes, short interfering RNA (siRNA), short interfering nucleic acid (siNA), and antisense which modulate the synthesis, expression and/or stability of an mRNA encoding one or more receptors of vascular endothelial growth factor, such as flt-1 (VEGFR1) and/or KDR (VEGFR2). Nucleic acid molecules and methods for the inhibition of angiogenesis and treatment of cancer and other conditions associated with VEGF-R are provided, optionally in conjunction with other therapeutic agents such as interferons.

1 . A method for down regulating expression of vascular endothelial growth factor receptors (VEGFRs) in an endothelial cell in vitro comprising contacting the cell with an enzymatic nucleic acid molecule that down regulates expression of VEGFR1 and an enzymatic nucleic acid molecule that down regulates expression of VEGFR2 under conditions suitable for down regulating expression of VEGFRs in the endothelial cell in vitro, wherein each of the enzymatic nucleic acid molecules contact the cell in the presence of a delivery reagent and wherein each of the enzymatic nucleic acid molecules have sufficient complementarity to VEGFR1 or VEGFR2 RNA for each of the enzymatic nucleic acid molecules to direct cleavage of the VEGFR1 or VEGFR2 RNA, wherein said VEGFR1 RNA comprises SEQ ID NO: 20823 and said VEGFR2 RNA comprises SEQ ID NO: 20824. 
     
     
         2 . The method of  claim 1 , wherein said endothelial cell is a mammalian cell. 
     
     
         3 . The method of  claim 1 , wherein said endothelial cell is a human cell. 
     
     
         4 . The method of  claim 1 , wherein said delivery reagent is a lipid. 
     
     
         5 . The method of  claim 4 , wherein said lipid is a cationic lipid. 
     
     
         6 . The method of  claim 1 , wherein said delivery reagent is a liposome.