Electro-transfer of small interfering RNA ameliorated arthritis in rats.
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.
Inoue
Atsuo
A
Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
Takahashi
Kenji A
KA
Mazda
Osam
O
Terauchi
Ryu
R
Arai
Yuji
Y
Kishida
Tsunao
T
Shin-Ya
Masaharu
M
Asada
Hidetsugu
H
Morihara
Toru
T
Tonomura
Hitoshi
H
Ohashi
Suzuyo
S
Kajikawa
Yoshiteru
Y
Kawahito
Yutaka
Y
Imanishi
Jiro
J
Kawata
Mitsuhiro
M
Kubo
Toshikazu
T
D000818:Animals; D001169:Arthritis, Experimental / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D018274:Electroporation; D049452:Green Fluorescent Proteins / Q000032:analysis / Q000235:genetics; D007719:Knee Joint / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics*; D051381:Rats; D013583:Synovial Membrane / Q000378:metabolism; D014161:Transduction, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha; D049452:Green Fluorescent Proteins