NF-kappaB oligonucleotide decoy molecules

Abstract

The present invention concerns double-stranded NF-κB decoy oligodeoxynucleotide (NF-κB dsODN) molecules that contain a core sequence capable of specific binding to an NF-κB transcription factor. In a particular aspect, the invention concerns NF-κB decoy molecules that preferentially bind p50/p65 and/or cRel/p50 heterodimers over p50/p50 homodimers. In another aspect, the invention concerns NF-κB decoy molecules with improved binding affinity to p65.

1 . A method for the treatment of an inflammatory bowel disease (IBD), comprising administering to a mammalian subject in need an effective amount of an NF-κB double-stranded decoy oligodeoxynucleotide (dsODN) molecule.  
     
     
         2 . The method of  claim 1  wherein said dsODN comprises in its sense strand, in 5′ to 3′ direction, the sequence of SEQ ID NO:30.  
     
     
         3 . The method of  claim 2  wherein the antisense strand of said dsODN molecule is at least partially complementary to said sense strand.  
     
     
         4 . The method of  claim 3  wherein the dsODN molecule further comprises at least one single-stranded overhang.  
     
     
         5 . The method of  claim 3  wherein the two strands of the dsODN are linked at the 5′ and/or 3′ end by a covalent bond, other than a peptide bond.  
     
     
         6 . The method of  claim 3  wherein the dsODN molecule comprises modified nucleotides.  
     
     
         7 . The method of  claim 3  wherein the dsODN molecule has a phosphodiester backbone.  
     
     
         8 . The method of  claim 3  wherein the dsODN molecule has a phosphorothioate backbone.  
     
     
         9 . The method of  claim 3  wherein the dsODN molecule has a mixed phosphodiester-phosphorothioate backbone.  
     
     
         10 . The method of  claim 2  wherein the antisense strand of said dsODN molecule is fully complementary to said sense strand.  
     
     
         11 . The method of  claim 2  wherein said dsODN molecule has a phosphodiesterate backbone.  
     
     
         12 . The method of  claim 2  wherein said dsODN molecule has a phosphorothioate backbone.  
     
     
         13 . The method of  claim 2  wherein said dsODN molecule has a mixed phosphodiesterate-phosphorothioate backbone.  
     
     
         14 . The method of  claim 2  wherein the sense and antisense strands are connected to each other solely by Watson-Crick base pairing.  
     
     
         15 . The method of  claim 2  wherein the sense and antisense strands are connected, completely or partially, by cross-links other than Watson-Crick base pairing.  
     
     
         16 . The method of  claim 2  wherein the sense and antisense strands are covalently linked to each other at their 3′ and/or 5′ end.  
     
     
         17 . The method of  claim 2  wherein the dsODN molecule comprises modified nucleotides.  
     
     
         18 . The method of  claim 1  wherein said mammalian subject is human.  
     
     
         19 . The method of  claim 1  wherein said dsODN molecule is administered by pressure mediated transfection.  
     
     
         20 . The method of  claim 1  wherein said dsODN molecule is administered by retroviral transfection.  
     
     
         21 . The method of  claim 1  wherein said dsODN molecule is administered in liposomes.  
     
     
         22 . The method of  claim 1  wherein said dsODN molecule is administered as a topical formulation.  
     
     
         23 . The method of  claim 1  wherein said dsODN molecule is administered as an oral formulation.