Transient activation of transgene expression by hydrodynamics-based injection may cause rapid decrease in plasmid DNA expression

Ochiai, Hiroshi; Fujimuro, Masahiro; Yokosawa, Hideyoshi; Harashima, Hideyoshi; Kamiya, Hiroyuki

Transient activation of transgene expression by hydrodynamics-based injection may cause rapid decrease in plasmid DNA expression

Ochiai, Hiroshi; Fujimuro, Masahiro; Yokosawa, Hideyoshi et al.

Gene therapy, 2007, 14(15), 1152-1159

Permalink : https://hdl.handle.net/2115/34648

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アクセス権	open access
URI	https://hdl.handle.net/2115/34648
タイトル	Transient activation of transgene expression by hydrodynamics-based injection may cause rapid decrease in plasmid DNA expression
その他のタイトル	Activation by hydrodynamics-based injection
著者	Ochiai, Hiroshi ; Fujimuro, Masahiro ; Yokosawa, Hideyoshi ; Harashima, Hideyoshi ; Kamiya, Hiroyuki
著者名 Ochiai, Hiroshi
著者名 Fujimuro, Masahiro
著者名 Yokosawa, Hideyoshi
e-Rad_Researcher 00183567 著者名 Harashima, Hideyoshi
著者名 Kamiya, Hiroyuki
言語	英語
キーワード	exogenous DNA
	histones
	intranuclear disposition
	silencing
	hydrodynamics-based injection
発行日	2007-08
出版者	Nature Publishing Group
収録物名	Gene therapy
巻(号)	14(15)
ページ	1152-1159
抄録	The intranuclear disposition of exogenous DNA is quite important for the therapeutic effects of the administered DNA. The expression efficiency from one copy of exogenous DNA delivered by hydrodynamics-based injection dramatically decreases over time, and this ‘silencing’ occurs without CpG methylation. In this study, naked luciferase-plasmid DNA was delivered into mouse liver by hydrodynamics-based injection, and modifications of the histones bound to the plasmid DNA were analyzed by a chromatin immunoprecipitation (ChIP) analysis. In addition, the effects of a second hydrodynamics-based injection on the expression from the plasmid DNA were examined. The ChIP analysis revealed that the modification status of histone H3 remained constant from 4 hr to 4 weeks. Surprisingly, the injection of saline without DNA enhanced the luciferase expression from the preexisting DNA administered 4 and 14 days previously. Our results suggest that histone modification plays no role in the silencing. Instead, our data suggest that the transgene expression is activated by the hydrodynamics-based injection manipulation, and that the return from the activated status causes the silencing.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
PISSN	0969-7128
関連情報	PMID 17525703
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1038/sj.gt.3302970