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 wi...

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Bibliographic Details
Published in:	Nucleic acids research Vol. 32; no. 13; p. e109
Main 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
Format:	Journal Article
Language:	English
Published:	England Oxford University Press 01-01-2004 Oxford Publishing Limited (England)
Subjects:	Animals Cell Division Cell Line, Tumor Collagen - administration & dosage Collagen - chemistry Humans Injections Male Mice Mice, Nude NAR Methods Online RNA Interference RNA Stability RNA, Small Interfering - biosynthesis RNA, Small Interfering - genetics RNA, Small Interfering - metabolism Testicular Neoplasms - pathology Testicular Neoplasms - therapy Transduction, Genetic - methods Xenograft Model Antitumor Assays
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Summary:	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.
Bibliography:	To whom correspondence should be addressed. Tel: +81 3 3542 2511; Fax: +81 3 3541 2685; Email: tochiya@ncc.go.jp ark:/67375/HXZ-6PHMQ0T5-L local:gnh093 Received April 8, 2004; Revised May 26, 2004; Accepted June 7, 2004 istex:C5041BACB4272AA4777F16CABE3311BA0C78F624 ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	0305-1048 1362-4962 1362-4962
DOI:	10.1093/nar/gnh093