おとり型核酸医薬による慢性関節リウマチに対する遺伝子治療

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  • <I>Application of NFκB decoy oligonucleotides for arthritis as a gene therapy</I>

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Rheumatoid arthritis (RA) and collagen-induced arthritis (CIA) are characterized by hyperplasia of the synovium and progressive joint destruction. The transcription factor-κB (NFκB) plays apivotal role in the coordinated transactivation of cytokine and adhesion molecule genes, whose activation has been postulated to be involved in destructive changes of articular cartilage and bone in arthritic joints. In particular, interleukin-1 (IL-1) and tumor necrosis factory α (TNFα) are important cytokines which perpetuate arthritis and induce joint destruction in both rheumatoid arthritis and collagen-induced arthritis. We hypothesized that synthetic double-stranded DNA high affinity for NFκB could be introduced in vivo as“decoy” cis elements to bind the transcription factor and to block the activation of proinflammatory cytokine genes such as IL-1 and TNFα. We reported here that in vivo transfection of NFκB decoy ODN by intraarticular injection into collagen-induced arthritis in rats improved paw swelling. Histologic and radiographic studies showed a marked suppression of joint destruction in ankles treated by NFκB decoy ODN transfection. NFκB decoy ODN also suppressed the production of IL-1 and TNFα by synovium in the arthritic joints. Results demonstrated that administration of NFκB decoy ODN in arthritic joints of collagen-induced arthritis in rats led to amelioration of arthritis. These findings suggest that intraarticular transfection of NFκB decoy ODN may provide a useful therapeutic strategy for inflammatory arthritis.

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  • 炎症・再生

    炎症・再生 21 (2), 101-108, 2001

    一般社団法人 日本炎症・再生医学会

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