Inhibitors of dek protein and related methods

Abstract

The present invention provides methods of treatment using inhibitors of DEK protein and DEK activity. Such methods include, but are not limited to, methods of preventing, treating, and/or ameliorating inflammatory diseases, infections, autoimmune diseases, malignant diseases, and other diseases or conditions in which DEK has been implicated. Such inhibitors of DEK protein include, but are not limited to, pharmaceutical compositions including single stranded DNA or RNA aptamers capable of binding to DEK. In some embodiments, such aptamers are useful for diagnosing DEK related diseases or conditions. Related kits and compositions are further provided.

We claim: 
     
         1 . A method of treating or ameliorating an inflammatory condition in a patient, comprising administering to said patient a therapeutically effective amount of a single-stranded anti-DEK DNA aptamer and a pharmaceutically acceptable carrier, wherein said anti-DEK DNA aptamer comprises 4 or less nucleotide substitutions, deletions, and/or insertions relative to a sequence of any one of SEQ ID NOs: 1, 2 and 6, wherein said anti-DEK DNA aptamer specifically binds DEK with an affinity (K d ) of less than 20 nM, and/or has DEK antagonist activity (IC 50 ) of less than 10 nM (10 −8 M). 
     
     
         2 . The method of  claim 1 , wherein said inflammatory condition is one or more conditions selected from arthritis, rheumatoid arthritis, juvenile rheumatoid arthritis, and inflammatory disease or an autoimmune disease. 
     
     
         3 . The method of  claim 1 , wherein said patient is a human patient and the DEK is human DEK. 
     
     
         4 . The method of  claim 1 , further comprising administering to said patient one or more anti-inflammatory agents. 
     
     
         5 . A kit comprising a pharmaceutical composition comprising a therapeutically effective amount of a single-stranded anti-DEK DNA aptamer, wherein said anti-DEK DNA aptamer comprises 4 or less nucleotide substitutions, deletions, and/or insertions relative to a sequence of any one of SEQ ID NOs: 1, 2 and 6, wherein said anti-DEK DNA aptamer specifically binds DEK with an affinity (K d ) of less than 20 nM, and/or has DEK antagonist activity (IC 50 ) of less than 10 nM (10 −8 M), optionally one or more anti-inflammatory agents, and instructions for administering said pharmaceutical composition to a patient diagnosed with arthritis, rheumatoid arthritis, juvenile rheumatoid arthritis, or uveitis. 
     
     
         6 . A composition comprising a therapeutically effective amount of a single-stranded anti-DEK DNA aptamer that specifically binds to DEK, wherein said anti-DEK DNA aptamer comprises 4 or less nucleotide substitutions, deletions, and/or insertions relative to a sequence of any one of SEQ ID NOs: 1, 2 and 6, wherein said anti-DEK DNA aptamer specifically binds DEK with an affinity (K d ) of less than 20 nM, and/or has DEK antagonist activity (IC 50 ) of less than 10 nM (10 −8 M).