염증성 질환 치료를 위한 비바이러스성 TACE(Tumor necrosis factor-α converting enzyme) 간섭 유전자 전달 시스템 개발에 관한 연구

Abstract

To date, many of the inflammatory diseases such as rheumatoid arthritis and inflammatory bowel diseases have been treated by blocking soluble tumor necrosis factor-alpha(s-TNF-α). Antibodies against TNF-α such as etanercept, infliximab and adalimumab have been prescribed for the treatment of diverse inflammatory diseases. Also, several studies using knockout model and RNAi for TNF-α inhibition have been come out. In recent studies, there have been some novel approaches for blocking TNF-α. For example, immune response is alleviated by inhibiting tumor necrosis factor-alpha converting enzyme(TACE). TACE, also called ADAM 17, is an enzyme involved in shedding of membrane-bound TNF-α. Released s-TNF-α induces further inflammatory responses. Actually, TACE is overexpressed in several inflammatory diseases. So, RNAi against TACE was used in this study for the treatment of inflammatory conditions. It is reported that rPOA has low cytotoxicity with high transfection efficiency for siRNA and DNA delivery. Applying this gene delivery carrier, TACE shRNA was effectively delivered to macrophage with low cytotoxicity. Through shRNA delivery, rPOA/shTACE expressed anti-inflammatory effect in vitro. It was demonstrated that rPOA is effective carrier for shRNA and is suitable for macrophage transfection. Thus, this delivery system could be applied to powerful gene therapy for inflammatory diseases.