A designed curved DNA sequence remarkably enhances transgene expression from plasmid DNA in mouse liver

S. Fukunaga, G. Kanda, J. Tanase, H. Harashima, T. Ohyama*, H. Kamiya

*この研究の対応する著者

研究成果: Article査読

12 被引用数 (Scopus)

抄録

The intranuclear disposition of plasmid DNA is extremely important for transgene expression. The interactions between the plasmid DNA and the histone proteins are one of the keys for controlling the disposition. In this study, the effects of a left-handedly curved sequence (20-40 repeated AT tracts) on transgene expression from a plasmid were examined in vivo. A naked luciferase plasmid with the curved sequence was delivered into mouse liver by a hydrodynamics-based injection, and the luciferase activities were quantitated at various time points. Interestingly, transgene expression was markedly increased by the addition of the curved sequence. An analysis of the nucleosome positions near the left-handedly curved sequence suggested that the sequence functions as an acceptor of the histone core and allows nucleosome sliding, resulting in transcriptional activation. These results suggested that the designed curved DNA sequences could control transgene expression from plasmid DNAs in vivo.

本文言語English
ページ(範囲)828-835
ページ数8
ジャーナルGene Therapy
19
8
DOI
出版ステータスPublished - 2012 8

ASJC Scopus subject areas

  • 分子医療
  • 分子生物学
  • 遺伝学

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