Highlighted paper selected by editor-in-chief: Intranuclear DNA release is a determinant of transfection activity for a non-viral vector: biocleavable polyrotaxane as a supramolecularly dissociative condenser for efficient intranuclear DNA release

  • Yamada Yuma
    Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido University
  • Nomura Taku
    Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido University
  • Harashima Hideyoshi
    Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido University
  • Yamashita Atsushi
    School of Materials Science, Japan Advanced Institute of Science and Technology
  • Katoono Ryo
    School of Materials Science, Japan Advanced Institute of Science and Technology
  • Yui Nobuhiko
    School of Materials Science, Japan Advanced Institute of Science and Technology

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  • Intranuclear DNA Release Is a Determinant of Transfection Activity for a Non-viral Vector: Biocleavable Polyrotaxane as a Supramolecularly Dissociative Condenser for Efficient Intranuclear DNA Release

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It has been believed that nuclear gene delivery is the most important process for gene expression, and various non-viral vectors are currently being developed with this assumption. However, some of our earlier studies revealed a surprising difference in transfection activity between viral and non-viral vectors: this difference is largely due to the result of the intranuclear disposition of DNA rather than its delivery to the nucleus (Hama S. et al. (2006), Quantitative comparison of intracellular trafficking and nuclear transcription between adenoviral and lipoplex systems. Mol. Ther., 13, 786—794). Here, we report on some direct evidence that demonstrates the importance of the release of intranuclear DNA on transfection activity. The data show that transfection activity can be substantially enhanced by integrating a multifunctional envelope-type nano device (MEND) and a biocleavable polyrotaxane (DMAE-SS-PRX) as an artificial condenser. Our integration system showed significantly higher transfection activity compared to conventional gene delivery system. Moreover, this system provides a strong support for our hypothesis that intranuclear DNA disposition plays a critical role in gene expression for non-viral vectors.

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