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

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)828-835
Number of pages8
JournalGene Therapy
Volume19
Issue number8
DOIs
Publication statusPublished - 2012 Aug

Keywords

  • exogenous DNA
  • histones
  • intranuclear disposition
  • left-handedly curved DNA
  • nucleosome

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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