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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概要
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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.
- 公益社団法人 日本薬学会の論文
著者
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Yamada Yuma
Laboratory For Molecular Design Of Pharmaceutics Faculty Of Pharmaceutical Sciences Hokkaido Univers
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HARASHIMA Hideyoshi
Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido Unive
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Harashima Hideyoshi
Laboratory For Molecular Design Of Pharmaceutics Faculty Of Pharmaceutical Sciences Hokkaido Univers
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KATOONO Ryo
School of Materials Science, Japan Advanced Institute of Science and Technology
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YUI Nobuhiko
School of Materials Science, Japan Advanced Institute of Science and Technology
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Katoono Ryo
School Of Materials Science Japan Advanced Institute Of Science And Technology
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Yui Nobuhiko
School Of Materials Science 21st Century Coe Program Japan Advanced Institute Of Science And Technol
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Nomura Taku
Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido Unive
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Yamashita Atsushi
School of Materials Science, Japan Advanced Institute of Science and Technology
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Yamashita Atsushi
School Of Materials Science Japan Advanced Institute Of Science And Technology
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Nomura Taku
Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido University
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