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Electro-transfer of small interfering RNA ameliorated arthritis in rats |
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| Authors: | Inoue Atsuo Takahashi Kenji A Mazda Osam Terauchi Ryu Arai Yuji Kishida Tsunao Shin-Ya Masaharu Asada Hidetsugu Morihara Toru Tonomura Hitoshi Ohashi Suzuyo Kajikawa Yoshiteru Kawahito Yutaka Imanishi Jiro Kawata Mitsuhiro Kubo Toshikazu |
| Affiliation: | Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan. |
| Abstract: | RNA interference provides the powerful means of sequence-specific gene silencing. Particularly, small interfering RNA (siRNA) duplexes may be potentially useful for therapeutic molecular targeting of human diseases, although novel delivery systems should be devised to achieve efficient and organ-specific transduction of siRNA. In the present study, we demonstrated that electro-transfer of a siRNA-polyamine complex made efficient and specific gene knockdown possible in the articular synovium. Targeted suppression of the tumor necrosis factor-alpha gene through this procedure significantly ameliorated collagen-induced arthritis in rats. Our results suggest the potential feasibility of therapeutic intervention with RNA medicines for treatment of rheumatoid and other locomotor diseases. |
| Keywords: | Arthritis Gene therapy Cytokine siRNA RNA interference Collagen-induced arthritis rat Synovial tissue Intra-articular injection In vivo electroporation Polyamine |
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