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Transient activation of transgene expression by hydrodynamics-based injection may cause rapid decrease in plasmid DNA expression
| 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)
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Submitter: 紙谷 浩之
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