SDF-1 Binding Nucleic Acids

Abstract

The present invention is related to an L nucleic acid that binds to an SDF-1.

1 . A nucleic acid molecule that binds SDF-1, selected from the group consisting of a type A nucleic acid molecule, a type B nucleic acid molecule, a type C nucleic acid molecule, SEQ ID NO:142, SEQ ID NO:143 and SEQ ID NP:144. 
     
     
         2 . The nucleic acid molecule according to  claim 1 , wherein said type A nucleic acid molecule comprises a core nucleotide sequence 5′AAAGYRACAHGUMAAX A UGAAAGGUARC 3′ (SEQ ID NO:19), wherein X A  is either absent or is A. 
     
     
         3 . The nucleic acid molecule according to  claim 2 , wherein said nucleic acid molecule comprises in 5′→3′ direction, a first stretch of nucleotides, the core nucleotide sequence, and a second stretch of nucleotides; or a second stretch of nucleotides, the core nucleotide sequence, and a first stretch of nucleotides. 
     
     
         4 . The nucleic acid molecule according to  claim 1 , wherein said type B nucleic acid molecule comprises a core nucleotide sequence: 
       
         
           
                 
               
                   (SEQ ID NO: 57) 
                 
                 
                 
               
                     
                   5′GUGUGAUCUAGAUGUADWGGCUGWUCCUAGUYAGG 3′. 
                 
             
                
               
            
             
                
               
            
           
         
       
     
     
         5 . The nucleic acid molecule according to  claim 4 , wherein said nucleic acid molecule comprises in 5′→3′ direction a first stretch of nucleotides, the core nucleotide sequence, and a second stretch of nucleotides; or a second stretch of nucleotides, the core nucleotide sequence, and a first stretch of nucleotides. 
     
     
         6 . The nucleic acid molecule according to  claim 1 , wherein said type C nucleic acid molecule comprises a core nucleotide sequence of GGUYAGGGCUHRX A AGUCGG (SEQ ID NO:90), wherein X A  is either absent or is A. 
     
     
         7 . The nucleic acid molecule according to  claim 6 , wherein said nucleic acid molecule comprises in 5′→3′ direction a first stretch of nucleotides, the core nucleotide sequence, and a second stretch of nucleotides; or a second stretch of nucleotides, the core nucleotide sequence, and a first stretch of nucleotides. 
     
     
         8 . The nucleic acid molecule according to  claim 1 , which is an antagonist of SDF-1. 
     
     
         9 . The nucleic acid molecule according to  claim 1 , wherein said SDF-1 comprises a human SDF-1. 
     
     
         10 . The nucleic acid molecule according to  claim 1 , wherein SDF-1 comprises SEQ ID NO:1. 
     
     
         11 . The nucleic acid according to  claim 1 , comprising a modification. 
     
     
         12 . The nucleic acid according to  claim 11 , wherein said modification comprises a HES moiety or a PEG moiety. 
     
     
         13 . The nucleic acid according to  claim 1 , comprising an L-nucleotide. 
     
     
         14 . A pharmaceutical composition for treating a disease comprising the nucleic acid molecule according to  claim 1  and a pharmaceutically acceptable excipient, and optionally a pharmaceutically active agent. 
     
     
         15 . The pharmaceutical composition of  claim 14 , wherein said disease is selected from the group consisting of a back-of-the-eye disease, diabetic retinopathy, age-related macular degeneration, cancer of breast, cancer of ovary, cancer of prostate, cancer of pancreas, cancer of thyroid, cancer of nasopharynx, cancer of colon, cancer of lung, cancer of stomach, osteosarcoma, melanoma, glioma, medulloblastoma, neuroblastoma, leukemia, WHIM syndrome, an immunologic deficiency syndrome, a pathologic neovascularization, an inflammation, multiple sclerosis, rheumatoid arthritis, osteoarthritis and nephritis. 
     
     
         16 . The pharmaceutical composition according to  claim 14 , wherein said disease comprises angiogenesis, neovascularization, inflammation or metastasis. 
     
     
         17 . A complex comprising SDF-1 and the nucleic acid according to  claim 1 . 
     
     
         18 . A method for screening of an SDF-1 antagonist or an SDF-1 agonist comprising the following steps:
 providing a candidate SDF-1 antagonist and/or a candidate SDF-lagonist,   providing the nucleic acid according to  claim 1 ,   providing a test system which provides a signal in the presence of an SDF-1 antagonist and/or an SDF-1 agonist, and   determining whether the candidate SDF-1 antagonist is a SDF-1 antagonist and/or whether the candidate SDF-1 agonist is a SDF-1 agonist.   
     
     
         19 . A method for the screening of an SDF-1 agonist and/or an SDF-1 antagonist comprising the following steps:
 providing SDF-1 immobilised to a phase,   providing the nucleic acid according to  claim 1 , which may be labelled,   adding a candidate SDF-1 agonist and/or a candidate SDF-1 antagonist, and   determining whether the candidate SDF-1 agonist is a SDF-1 agonist and/or whether the candidate SDF-1 antagonist is a SDF-1 antagonist.   
     
     
         20 . A kit for the detection of SDF-1, comprising the nucleic acid according to  claim 1 .