SDF-1 Binding Nucleic Acids and the Use Thereof

Abstract

The present invention is related to a nucleic acid molecule binding to SDF-1, whereby the nucleic acid molecule influences migration of cells.

1 - 115 . (canceled) 
     
     
         116 . A method for the treatment of nephropathy or hypertension, wherein the method comprises administering to a subject in need of treatment, a nucleic acid that inhibits the signalling between SDF-1 and the SDF-1 receptor. 
     
     
         117 . The method according to  claim 116 , wherein said nephropathy comprises diabetic nephropathy. 
     
     
         118 . The method according to  claim 116 , wherein the nucleic acid comprises an SDF-1 binding molecule or an SDF-1 receptor binding molecule. 
     
     
         119 . The method according to  claim 118 , wherein the SDF-1 binding molecule or the SDF-1 receptor binding molecule is selected from the group consisting of an aptamer, a Spiegelmer, an antibody and a small molecule. 
     
     
         120 . The method according to  claim 118 , wherein the SDF-1 binding molecule or the SDF-1 receptor binding molecule is selected from the group consisting of a type A nucleic acid, a type B nucleic acid, a type C nucleic acid, SEQ ID NO:142, SEQ ID NO: 143 and SEQ ID NO:144,
 wherein the type A nucleic acid comprises a core nucleotide sequence:   
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 19) 
                 
                     
                   5′ AAAGYRACAHGUMAAX A UGAAAGGUARC 3′  
                 
             
                
                
               
            
           
         
         wherein X A  is either absent or is A, 
         wherein the type B nucleic acid comprises a core nucleotide sequence: 
       
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 57) 
                 
                     
                   5′ GUGUGAUCUAGAUGUADWGGCUGWUCCUAGUYAGG 3′ 
                 
             
                
                
               
            
           
         
       
       and
 wherein the type C nucleic acid comprises a core nucleotide sequence: 
 
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 90) 
                 
                     
                   5′ GGUUYAGGGCUHRX A AGUCGG 3′, 
                 
             
                
                
               
            
           
         
         wherein X A  is either absent or is A. 
       
     
     
         121 . The method according to  claim 120 , wherein the
 the type A nucleic acid comprises a nucleotide sequence according to any one of SEQ ID NOs:5 to 18, 25 to 41, 133, 137, 139, 140 or 141;   the nucleic type B acid comprises a nucleotide sequence according to any one of SEQ ID NOs:46 to 56, 61 to 72 or 132; and   the type C nucleic acid comprises a nucleotide sequence according to any one of SEQ ID NOs:79 to 89, 94 to 119, 134, 135 or 136.   
     
     
         122 . The method according to  claim 116 , wherein the nucleic acid comprises an antagonist of the SDF-1 receptor system, wherein the SDF-1 receptor of the SDF-1 receptor system comprises CXCR4 or CXCR7. 
     
     
         123 . The method according to  claim 116 , wherein the SDF-1 is a human SDF-1 or the SDF-1 receptor is a human SDF-1 receptor. 
     
     
         124 . The method according to  claim 116 , wherein the nucleic acid comprises a modification. 
     
     
         125 . The method according to  claim 124 , wherein the modification is selected from the group consisting of a HES moiety and a PEG moiety. 
     
     
         126 . The method according to  claim 124 , wherein the modification comprises a PEG moiety consisting of a straight or branched PEG, wherein the molecular weight of the PEG moiety is from about 2 to 180 kD, 60 to 140 kD or about 40 kD. 
     
     
         127 . The method according to  claim 116 , wherein the nucleic acid inhibits expression of SDF-1 or SDF-1 receptor and comprises siRNA molecules, ribozymes, antisense molecules or inhibitors of transcription factors. 
     
     
         128 . The method according to  claim 116 , wherein said hypertension comprises pulmonary hypertension. 
     
     
         129 . A method for inhibiting the migration of leukocytes, wherein the method comprises administering to a subject in need of treatment a nucleic acid that inhibits signalling between SDF-1 and the SDF-1 receptor selected from the group consisting of a type A nucleic acid, a type B nucleic acid, a type C nucleic acid, SEQ ID NO:142, SEQ ID NO: 143 and SEQ ID N:144,
 wherein the type A nucleic acid comprises a core nucleotide sequence:   
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 19) 
                 
                     
                   5′ AAAGYRACAHGUMAAX A UGAAAGGUARC 3′ 
                 
             
                
                
               
            
           
         
       
       wherein X A  is either absent or is A,
 wherein the type B nucleic acid molecule comprises a core nucleotide sequence: 
 
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 57) 
                 
                     
                   5′ GUGUGAUCUAGAUGUADWGGCUGWUCCUAGUYAGG 3′; 
                 
             
                
                
               
            
           
         
       
       and
 wherein the type C nucleic acid molecule comprises a core nucleotide sequence of 
 
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 90) 
                 
                     
                   GGUYAGGGCUHR X AAGUCGG, 
                 
             
                
                
               
            
           
         
       
       wherein X A  is either absent or is A. 
     
     
         130 . The method according to  claim 129 , wherein the
 the type A nucleic acid comprises a nucleotide sequence according to any one of SEQ ID NOs:5 to 18, 25 to 41, 133, 137, 139, 140 or 141;   the nucleic type B acid comprises a nucleotide sequence according to any one of SEQ ID NOs:46 to 56, 61 to 72 or 132; and   the type C nucleic acid comprises a nucleotide sequence according to any one of SEQ ID NOs:79 to 89, 94 to 119, 134, 135 or 136.   
     
     
         131 . The method according to  claim 129 , wherein the nucleic acid comprises an antagonist of the SDF-1 receptor system, wherein the SDF-1 receptor of the SDF-11 receptor system comprises CXCR4 or CXCR7. 
     
     
         132 . The method according to  claim 129 , wherein the SDF-1 is a human SDF-1 or the SDF-1 receptor of the SDF-1 receptor system is a human SDF-1 receptor. 
     
     
         133 . The method according to  claim 129 , wherein the nucleic acid comprises a modification. 
     
     
         134 . The method according to  claim 133 , wherein the modification is selected from the group consisting of a HES moiety and a PEG moiety. 
     
     
         135 . The method according to  claim 133 , wherein the modification comprises a PEG moiety consisting of a straight or branched PEG, wherein the molecular weight of the PEG moiety is from about 2 to 180 kD, from about 60 to 140 kD or about 40 kD.