RNA interference in vitro and in vivo using an arginine peptide/siRNA complex system.
Efficient delivery systems are required to exploit the enormous potential of RNA interference. We introduced an arginine peptide-based small-interference RNA (siRNA) delivery system for in vitro and in vivo RNA interference. Arginine peptides formed stable complexes with siRNA and transduced siRNA into COS-7 cells in vitro, resulting in efficient gene silencing. The intracellular path of the peptide/siRNA complex was investigated in live cells using fluorescent labeling and confocal microscopy. At 24h after transfection, most of the siRNA signals were observed in the perinuclear region, indicating that siRNA was targeted to the perinuclear region for interactions with RNA-induced silencing complex (RISC). Effective in vivo RNA interference was achieved in a mouse model bearing a subcutaneous tumor. Intratumoral administration of HER-2-specific siRNA/peptide complexes resulted in a marked reduction of tumor growth. Body weight monitoring during treatment showed that our delivery system was nontoxic. Our approach offers the potential for siRNA delivery in various in vitro and in vivo applications.
Kim
Sung Wook
SW
Department of Life Science, Sogang University, Shinsu-Dong, Mapo, Seoul 121-742, South Korea.
Kim
Na Young
NY
Choi
Yu Bin
YB
Park
Seo Hyun
SH
Yang
Jai Myung
JM
Shin
Sungho
S
D000818:Animals; D001120:Arginine / Q000737:chemistry*; D019556:COS Cells; D002522:Chlorocebus aethiops; D018734:Genes, erbB-2; D015316:Genetic Therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000628:therapy*; D010455:Peptides / Q000737:chemistry*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*
D010455:Peptides; D034741:RNA, Small Interfering; D001120:Arginine