Electro-transfer of small interfering RNA ameliorated arthritis in rats

被引:57
作者
Inoue, A
Takahashi, KA [1 ]
Mazda, O
Terauchi, R
Arai, Y
Kishida, T
Shin-Ya, M
Asada, H
Morihara, T
Tonomura, H
Ohashi, S
Kajikawa, Y
Kawahito, Y
Imanishi, J
Kawata, M
Kubo, T
机构
[1] Kyoto Prefectural Univ Med, Dept Orthopaed, Grad Sch Med Sci, Kamikyo Ku, Kyoto 6028566, Japan
[2] Kyoto Prefectural Univ Med, Dept Microbiol, Grad Sch Med Sci, Kamikyo Ku, Kyoto 6028566, Japan
[3] Kyoto Prefectural Univ Med, Dept Inflaammat & Immunol, Grad Sch Med Sci, Kamikyo Ku, Kyoto 6028566, Japan
[4] Kyoto Prefectural Univ Med, Dept Anat & Neurobiol, Grad Sch Med Sci, Kamikyo Ku, Kyoto 6028566, Japan
[5] Louis Pasteur Ctr Med Res, Kyoto 6068225, Japan
关键词
arthritis; gene therapy; cytokine; siRNA; RNA interference; collagen-induced arthritis rat; synovial tissue; intra-articular injection; in vivo electroporation; polyamine;
D O I
10.1016/j.bbrc.2005.08.198
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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. sigma 2005 Elsevier Inc. All rights reserved.
引用
收藏
页码:903 / 908
页数:6
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