Atelocollagen-mediated synthetic small interfering RNA delivery for effective gene silencing in vitro and in vivo.
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.
Minakuchi
Yoshiko
Y
Formulation Research Laboratories, Sumitomo Pharmaceuticals Co. Ltd, Osaka 567-0878, Japan.
Takeshita
Fumitaka
F
Kosaka
Nobuyoshi
N
Sasaki
Hideo
H
Yamamoto
Yusuke
Y
Kouno
Makiko
M
Honma
Kimi
K
Nagahara
Shunji
S
Hanai
Koji
K
Sano
Akihiko
A
Kato
Takashi
T
Terada
Masaaki
M
Ochiya
Takahiro
T
D000818:Animals; D002455:Cell Division; D045744:Cell Line, Tumor; D003094:Collagen / Q000008:administration & dosage / Q000737:chemistry*; D006801:Humans; D007267:Injections; D008297:Male; D051379:Mice; D008819:Mice, Nude; D034622:RNA Interference; D020871:RNA Stability; D034741:RNA, Small Interfering / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D013736:Testicular Neoplasms / Q000473:pathology / Q000628:therapy; D014161:Transduction, Genetic / Q000379:methods*; D023041:Xenograft Model Antitumor Assays
D034741:RNA, Small Interfering; C059821:atelocollagen; D003094:Collagen