Tenascin-C nucleic acid ligands

Abstract

Methods are described for the identification and preparation of nucleic acid ligands to tenascin-C. Included in the invention are specific RNA ligands to tenascin-C identified by the SELEX method. Further included in the invention are methods for detecting the presence of a disease condition in a biological tissue in which tenascin-C is expressed.

1 . A method for detecting the presence of a disease in a biological tissue which may contain said disease, wherein said disease is characterized by the expression of tenascin-C in said tissue and wherein said disease is selected from the group consisting of cancer, psoriasis, and atherosclerosis, the method comprising: 
 a) attaching a marker that can be used in in vivo diagnostics to a tenascin-C nucleic acid ligand to form a marker-nucleic acid ligand complex;    b) exposing said biological tissue which may contain said disease to said marker-nucleic acid ligand complex; and    c) detecting the presence of said disease in said tissue by detecting the presence of said marker-nucleic acid ligand in said tissue.    
     
     
         2 . The method of  claim 1  wherein said marker is selected from the group consisting of radionuclides, fluorophores, magnetic compounds, and biotin.  
     
     
         3 . The method of  claim 2  wherein said radionuclide is selected from the group consisting of technetium-99m (Tc-99m), Re-188, Cu-64, Cu-67, F-18,  125 I,  131 I,  111 In,  32 P, and  186 Re.  
     
     
         4 . The method of  claim 3  wherein said marker is technetium-99m.  
     
     
         5 . The method of  claim 1  wherein said tenascin-C nucleic acid ligand comprises a linker.  
     
     
         6 . The method of  claim 5  wherein said linker is (CH 2 CH 2 O) 6 .  
     
     
         7 . The method of  claim 5  wherein said linker has the structure  
       
         
           
           
               
               
           
         
       
     
     
         8 . The method of  claim 5  wherein said technetium-99m is associated with a chelator.  
     
     
         9 . The method of  claim 1  further comprising attaching a therapeutic or diagnostic agent to said complex.  
     
     
         10 . The method of  claim 1  wherein said disease is cancer.  
     
     
         11 . The method of  claim 1  wherein said tenascin-C nucleic acid ligand is identified by: 
 i) contacting a candidate mixture of nucleic acids with tenascin-C wherein nucleic acids having an increased affinity to tenascin-C relative to the candidate mixture may be partitioned from the remainder of the candidate mixture;    ii) partitioning the increased affinity nucleic acids from the remainder of the candidate mixture;    iii) amplifying the increased affinity nucleic acids to yield a mixture of nucleic acids with relatively higher affinity and specificity for binding to tenascin-c, whereby a nucleic acid ligand of tenascin-c is identified.