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- κ B is an intensively studied transcription factor well known for its role in stimulating the production of inflammatory cytokines. Recently, NF- κ B decoy nucleic acids have gained considerable attention as potential therapeutics for inflammatory disease due to their ability to inhibit NF- κ B-mediated production of inflammatory cytokines, by preventing NF- κ B from binding to its native DNA binding sites. Preliminary studies with NF- κ B decoys indicate efficacy in reducing both pain and itch.
First generation NF- κ 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- κ B decoy was developed with improved nuclease resistance and significantly longer half-life.