Transient activation of transgene expression by hydrodynamics-based injection may cause rapid decrease in plasmid DNA expression
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概要
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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.
- Nature Publishing Groupの論文
著者
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Kiwada Hiroshi
Department Of Pharmacokinetics And Biopharmaceutics Faculty Of Pharmaceutical Sciences The Universit
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Kamiya Hiroyuki
Lab. For Molecular Design Of Pharmaceutics Fac. Of Pharmaceutical Sciences Hokkaido Univ.
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Murata-kamiya Naoko
Inst. Indust. Ecolog. Sci. Univ. Occup. Environ. Hith.
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Kamiya Hiroyuki
Faculty Of Pharmaceutical Sciences Hokkaido University:crest Japan Science And Technology
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Ochiai Hiroshi
Faculty Of Pharmaceutical Sciences Hokkaido University
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