このアイテムのアクセス数: 123

このアイテムのファイル:
ファイル 記述 サイズフォーマット 
pharmaceutics7030199.pdf976 kBAdobe PDF見る/開く
タイトル: Contribution of Epigenetic Modifications to the Decline in Transgene Expression from Plasmid DNA in Mouse Liver.
著者: Zang, Lei
Nishikawa, Makiya
Ando, Mitsuru
Takahashi, Yuki  kyouindb  KAKEN_id
Takakura, Yoshinobu  kyouindb  KAKEN_id
著者名の別形: 西川, 元也
キーワード: transgene expression
CpG
DNA methylation
histone deacetylation
hydrodynamic injection
発行日: 7-Aug-2015
出版者: MDPI
誌名: Pharmaceutics
巻: 7
号: 3
開始ページ: 199
終了ページ: 212
抄録: Short-term expression of transgenes is one of the problems frequently associated with non-viral in vivo gene transfer. To obtain experimental evidence for the design of sustainable transgene expression systems, the contribution of epigenetic modifications to the decline in transgene expression needs to be investigated. Bisulfite sequencing and reactivation by hydrodynamic injection of isotonic solution were employed to investigate methylation statues of CpG in transiently expressing plasmid, pCMV-Luc, in mouse liver after hydrodynamic delivery. The cytosines of CpGs in the promoter region of pCMV-Luc were methylated in mouse liver, but the methylation was much later than the decline in the expression. The expression from pre-methylated pCMV-Luc was insensitive to reactivation. Neither an inhibitor of DNA methylation nor an inhibitor of histone deacetylation had significant effects on transgene expression after hydrodynamic injection of pCMV-Luc. Partial hepatectomy, which reduces the transgene expression from the non-integrated vector into the genome, significantly reduced the transgene expression of human interferon γ from a long-term expressing plasmid pCpG-Huγ, suggesting that the CpG-reduced plasmid was not significantly integrated into the genomic DNA. These results indicate that the CpG-reduced plasmids achieve prolonged transgene expression without integration into the host genome, although the methylation status of CpG sequences in plasmids will not be associated with the prolonged expression.
著作権等: This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
URI: http://hdl.handle.net/2433/202025
DOI(出版社版): 10.3390/pharmaceutics7030199
PubMed ID: 26262639
出現コレクション:学術雑誌掲載論文等

アイテムの詳細レコードを表示する

Export to RefWorks


出力フォーマット 


このリポジトリに保管されているアイテムはすべて著作権により保護されています。