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

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Please use this identifier to cite or link to this item:http://hdl.handle.net/2115/34648

Title: Transient activation of transgene expression by hydrodynamics-based injection may cause rapid decrease in plasmid DNA expression
Other Titles: Activation by hydrodynamics-based injection
Authors: Ochiai, Hiroshi Browse this author
Fujimuro, Masahiro Browse this author
Yokosawa, Hideyoshi Browse this author
Harashima, Hideyoshi Browse this author →KAKEN DB
Kamiya, Hiroyuki Browse this author
Keywords: exogenous DNA
histones
intranuclear disposition
silencing
hydrodynamics-based injection
Issue Date: Aug-2007
Publisher: Nature Publishing Group
Journal Title: Gene therapy
Volume: 14
Issue: 15
Start Page: 1152
End Page: 1159
Publisher DOI: 10.1038/sj.gt.3302970
PMID: 17525703
Abstract: 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.
Type: article (author version)
URI: http://hdl.handle.net/2115/34648
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 紙谷 浩之

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