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 treatment of a patient with an inflammatory condition, comprising:
 a) generating a high affinity aptamer specific for a DEK target sequence by the steps of:
 1) identifying a DEK target molecule; 
 2) generating a high affinity aptamer specific for said DEK target molecule by systematic evolution of ligands by exponential enrichment (SELEX), comprising:
 i) preparing a mixture of nucleotides comprising random sequence; 
 ii) binding said mixture of nucleotides comprising random sequence to the said DEK target molecule to form an affinity complex; 
 iii) separating said affinity complex from unbound nucleotides comprising random sequence; 
 iv) separating and isolating at least one bound nucleotide comprising random sequence from said affinity complex; 
 v) purifying said at least one separated and isolated nucleotide comprising random sequence thereby generating a high affinity aptamer specific for said DEK molecule; and 
 
   b) treating said patient with said inflammatory condition with a therapeutically effective amount said high affinity aptamer specific for said DEK target molecule to treat said patient with said inflammatory condition.   
     
     
         2 . The method of  claim 1 , wherein said patient is a mammal, a human, a cat, a dot, a horse, a pig, a domestic animal, a wild animal, livestock or cattle. 
     
     
         3 . The method of  claim 1 , wherein said inflammatory condition is an acute inflammatory condition, a chronic inflammatory condition, rheumatoid arthritis, juvenile idiopathic arthritis, systemic-onset juvenile idiopathic arthritis, or osteoarthritis. 
     
     
         4 . The method of  claim 1 , wherein said nucleotides are DNA nucleotides. 
     
     
         5 . The method of  claim 1 , wherein said nucleotides are single-stranded nucleotides. 
     
     
         6 . The method of  claim 1 , comprising one or more amplification steps between steps i) to v). 
     
     
         7 . The method of  claim 1 , wherein said high affinity aptamer specific for said DEK target molecule is covalently bound to said DEK target molecule. 
     
     
         7 . The method of  claim 1 , wherein said high affinity aptamer specific for said DEK target molecule comprises one or more modified nucleotides. 
     
     
         8 . The method of  claim 7 , wherein said one or more modified nucleotides comprise one or more substitutions at the ribose and/or phosphate base positions. 
     
     
         9 . The method of  claim 7 , wherein said one more modified nucleotides comprise at least one modified pyrimidine. 
     
     
         10 . The method of  claim 9 , wherein said one more modified nucleotides comprise at least one aromatic modified pyrimidine. 
     
     
         11 . The method of  claim 1 , wherein said high affinity aptamer specific for said DEK target molecule is administered with an anti-inflammatory agent. 
     
     
         12 . The method of  claim 1 , wherein said high affinity aptamer specific for said DEK target molecule is administered with a pharmaceutically acceptable carrier.