Description
NF-(KAPPA)B decoy oligodeoxynucleotides Painful inflammatory diseases such as rheumatoid arthritis and atopic dermatitis are currently treated primarily symptomatically, through the use of analgesics. Thus, there is a great need for novel therapeutics targeting the underlying inflammatory mechanisms. NF-(KAPPA)B is an intensively studied transcription factor well known for its role in stimulating the production of inflammatory cytokines. Recently, NF-(KAPPA)B decoy nucleic acids have gained considerable attention as potential therapeutics for inflammatory disease due to their ability to inhibit NF-(KAPPA)B-mediated production of inflammatory cytokines, by preventing NF-(KAPPA)B from binding to its native DNA binding sites. Preliminary studies with NF-(KAPPA)B decoys indicate efficacy in reducing both pain and itch.
First generation NF-(KAPPA)B decoy nucleic acid drugs were linear DNA duplexes. Such drugs suffered not only from poor cellular uptake, but also from serum half-life due to poor resistance to nucleases. Subsequently, a circular (ribbon) form of NF-(KAPPA)B decoy was developed with improved nuclease resistance and significantly longer half-life.
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First generation NF-(KAPPA)B decoy nucleic acid drugs were linear DNA duplexes. Such drugs suffered not only from poor cellular uptake, but also from serum half-life due to poor resistance to nucleases. Subsequently, a circular (ribbon) form of NF-(KAPPA)B decoy was developed with improved nuclease resistance and significantly longer half-life.
