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

Gene Therapy volume 19, pages 828–835 (2012)Cite this article

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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 A•T 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.

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Acknowledgements

This work was supported in part by Grants-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and the Japan Society for the Promotion of Science.

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Author notes

  1. S Fukunaga, G Kanda and J Tanase: These authors contributed equally to this work.

Authors and Affiliations

  1. Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan

    S Fukunaga, G Kanda, H Harashima & H Kamiya

  2. CREST, Japan Science and Technology, Japan

    G Kanda, H Harashima & H Kamiya

  3. Faculty of Education and Integrated Arts and Sciences, Major in Integrative Bioscience and Biomedical Engineering, Graduate School of Science and Engineering, Waseda University, Tokyo, Japan

    J Tanase & T Ohyama

  4. Graduate School of Science and Engineering, Ehime University, Matsuyama, Japan

    H Kamiya

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  1. S Fukunaga
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  2. G Kanda
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  4. H Harashima
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  5. T Ohyama
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  6. H Kamiya
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Correspondence to T Ohyama or H Kamiya.

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Fukunaga, S., Kanda, G., Tanase, J. et al. A designed curved DNA sequence remarkably enhances transgene expression from plasmid DNA in mouse liver. Gene Ther 19, 828–835 (2012). https://doi.org/10.1038/gt.2011.127

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  • DOI: https://doi.org/10.1038/gt.2011.127

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