Development of inflammatory cell-specific gene regulation system for gene therapeutic strategy

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We proposed a novel strategy called D-RECS (drug or gene delivery system responding to cellular signals) to convert an intracellular signal to transgene expression. Here we apply this concept to inflammatory cells by using Ix-B kinase as a signal molecule that triggers the gene expression. Candidate cationic substrates of Ix-B kinase beta (IKK.(3) were synthesized and their reactivity was investigated. The results of gel shift assay showed that the polyplex was disintegrated and free DNA was released in the presence of IKKf3. The polyplex comprising CMV-GFP plasmid DNA and the polymer expressed the transgene in living cells exposed to a pro-inflammatory stimulus. Our concept of cell-specific gene expression was proved to work in inflammatory cells. This method may provide a unique strategy for gene therapy exclusively in inflammatory cells.