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

S. Fukunaga, G. Kanda, J. Tanase, H. Harashima, Takashi 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

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    Keywords

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

    ASJC Scopus subject areas

    • Molecular Medicine
    • Molecular Biology
    • Genetics

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