High affinity oligonucleotide ligands to growth factors

Abstract

Methods are described for the identification and preparation of high-affinity nucleic acid ligands to TGFβ, PDGF and hKGF. Included in the invention are specific RNA and ssDNA ligands to TGFβ1 and PDGF identified by the SELEX method. Also included in the invention are specific RNA ligands to hKGF identified by the SELEX method. Further included are RNA ligands that inhibit the interaction of TGFβ1 and hKGF with their receptors and DNA ligands that inhibit the interaction of PDGF with its receptor.

1 . A method of inhibiting a platelet derived growth factor (PDGF) comprising contacting said PDGF with a nucleic acid ligand of PDGF.  
     
     
         2 . The method of  claim 1 , wherein the nucleic acid ligand of PDGF comprises a ligand selected from the group of sequences consisting of SEQ ID NOS:93-124 and 128-176.  
     
     
         3 . A method for treating a PDGF mediated disease or medical condition comprising administering to a patient in need thereof a pharmaceutically effective amount of a nucleic acid ligand capable of binding to PDGF.  
     
     
         4 . The method of  claim 3 , wherein the nucleic acid ligand of PDGF comprises a ligand selected from the group of sequences consisting of SEQ ID NOS:93-124 and 128-176.  
     
     
         5 . The method of  claim 3 , wherein said PDGF mediated disease or medical condition is a proliferative disease.  
     
     
         6 . The method of  claim 5 , wherein said proliferative disease is a tumor expressing PDGF or PDGF receptors.  
     
     
         7 . A method of inhibiting a human keratinocyte growth factor (hKGF) comprising contacting said hKGF with a nucleic acid ligand of hKGF.  
     
     
         8 . The method of  claim 7 , wherein the nucleic acid ligand of hKGF comprises a ligand selected from the group of sequences consisting of SEQ ID NOS:189-264 and 268-304.  
     
     
         9 . A method for treating a hKGF mediated disease or medical condition comprising administering to a patient in need thereof a pharmaceutically effective amount of a nucleic acid ligand capable of binding to hKGF.  
     
     
         10 . The method of  claim 9 , wherein the nucleic acid ligand of hKGF comprises a ligand selected from the group of sequences consisting of SEQ ID NOS: 189-264 and 268-304.  
     
     
         11 . The method of  claim 9 , wherein said hKGF mediated disease or medical condition is select.