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Atelocollagen-mediated synthetic small interfering RNA delivery for effective gene silencing in vitro and in vivo
Authors:Minakuchi Yoshiko  Takeshita Fumitaka  Kosaka Nobuyoshi  Sasaki Hideo  Yamamoto Yusuke  Kouno Makiko  Honma Kimi  Nagahara Shunji  Hanai Koji  Sano Akihiko  Kato Takashi  Terada Masaaki  Ochiya Takahiro
Institution:Formulation Research Laboratories, Sumitomo Pharmaceuticals Co. Ltd, Osaka 567-0878, Japan.
Abstract:Silencing gene expression by siRNAs is rapidly becoming a powerful tool for the genetic analysis of mammalian cells. However, the rapid degradation of siRNA and the limited duration of its action call for an efficient delivery technology. Accordingly, we describe here that Atelocollagen complexed with siRNA is resistant to nucleases and is efficiently transduced into cells, thereby allowing long-term gene silencing. Site-specific in vivo administration of an anti-luciferase siRNA/Atelocollagen complex reduced luciferase expression in a xenografted tumor. Furthermore, Atelocollagen-mediated transfer of siRNA in vivo showed efficient inhibition of tumor growth in an orthotopic xenograft model of a human non-seminomatous germ cell tumor. Thus, for clinical applications of siRNA, an Atelocollagen-based non-viral delivery method could be a reliable approach to achieve maximal function of siRNA in vivo.
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