Nucleic acid ligands to ll37

Abstract

The present invention is directed to nucleic acid ligands to LL37, methods for producing said nucleic acid ligands, and methods for utilizing said nucleic acid ligands. In one exemplary embodiment, for example, this invention relates to nucleic acid ligands exhibiting high specific binding affinity to LL37 peptides, precursors and/or portions thereof. Further, the nucleic acid ligands may bind competitively with native ligands of LL37 and may also inhibit and/or interfere with LL37 function, such as by binding to LL37.

1 . A composition comprising:
 at least one modified aptamer having a specific binding affinity to human LL37, said at least one modified aptamer comprising at least one higher-order-bond modified nucleobase; wherein said specific binding affinity substantially inhibits the function of said human LL37.   
     
     
         2 . The composition of  claim 1 , wherein said at least one higher-order-bond modified nucleobase comprises an alkyne-modified nucleobase. 
     
     
         3 . The composition of  claim 2 , wherein said alkyne-modified nucleobase is selected from the group consisting of Amino-allyl deoxyUTP, 5-Propynyl-2′-deoxycytidine-5′-Triphosphate, and C8-alkyne-dCTP. 
     
     
         4 . The composition of  claim 1 , wherein said at least one modified nucleic acid ligand comprises an aptamer substantially homologous to Sequence ID SEQ7. 
     
     
         5 . The composition of  claim 1 , further comprising a solvent, wherein said at least one modified nucleic acid ligand is substantially dissolved in said solvent. 
     
     
         6 . The composition of  claim 5 , wherein said solvent comprises DMSO. 
     
     
         7 . The composition of  claim 1 , wherein said at least one modified nucleic acid ligand comprises a multimeric aptamer comprising at least two aptamers. 
     
     
         8 . The composition of  claim 7 , wherein said multimeric aptamer comprises a chimeric aptamer. 
     
     
         9 . The composition of  claim 7 , wherein said at least two aptamers are linked by a polymeric linkage. 
     
     
         10 . The composition of  claim 9 , wherein said polymeric linkage comprises an oligonucleotide linkage. 
     
     
         11 . A method for treatment of a human comprising:
 applying a composition to a human tissue experiencing psoriasis or rosacea to prevent DNA-mediated activation of plasmacytoid dendritic cells by human LL37 peptide, said composition comprising at least one modified aptamer having a non-naturally derived single stranded DNA sequence which produces a secondary structure with a specific binding affinity to said human LL37 peptide and which is incapable of triggering said DNA-mediated activation of plasmacytoid dendritic cells by said human LL37 peptide, said at least one modified aptamer comprising at least one high-order-bond modified nucleobase;   
       wherein said at least one high-order-bond modified nucleobase increases transport of said composition into or across said human tissue. 
     
     
         12 . The method of  claim 11 , wherein said at least one modified nucleic acid ligand binds to and substantially inhibits said human LL37. 
     
     
         13 . The method of  claim 11 , wherein said increased transport comprises increased solubility of said composition in lipid-rich or proteinaceous tissue. 
     
     
         14 . The method of  claim 11 , wherein said at least one high-order-bond modified nucleobase comprises an alkyne-modified nucleobase. 
     
     
         15 . The method of  claim 14 , wherein said alkyne-modified nucleobase is selected from the group consisting of Amino-allyl deoxyUTP, 5-Propynyl-2′-deoxycytidine-5′-Triphosphate, and C8-alkyne-dCTP. 
     
     
         16 . The method of  claim 11 , further comprising applying a solvent to said human tissue. 
     
     
         17 . The method of  claim 11 , wherein said human tissue comprises skin. 
     
     
         18 . A composition comprising:
 at least one modified nucleic acid ligand substantially homologous to Sequence ID SEQ7.   
     
     
         19 . The composition of  claim 18 , wherein said at least one modified nucleic acid ligand comprises at least one alkyne-modified nucleobase. 
     
     
         20 . The composition of  claim 19 , wherein said alkyne-modified nucleobase is selected from the group consisting of Amino-allyl deoxyUTP, 5-Propynyl-2′-deoxycytidine-5′-Triphosphate, and C8-alkyne-dCTP.