Key Physiological Phenomena Governing Transgene Expression Based on Tissue Pressure-Mediated Transfection in Mice
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概要
- 論文の詳細を見る
It is generally recognized that in vivo gene transfection is one of the most important techniques used in the post-genome era. Above all, naked plasmid DNA transfection has attracted much attention because of its advantages including convenience of preparation and handling and lack of toxicity associated with the transfection agents. We have investigated tissue pressure-mediated transfection performed by light and controlled pressure of the target tissue after normal intravenous injection of plasmid DNA. So far, we have demonstrated that plasmid DNA and small-interfering RNA (siRNA) are very efficiently transfected into murine kidney, liver and spleen without causing marked tissue damage. In this study, in order to understand the key physiological phenomena affecting transgene expression, we performed a set of experiments involving tissue pressure-mediated transfection, including the biodistribution and cellular transport of plasmid DNA and activation of transcriptional factors and obtained the following results: i) plasmid DNA transfer to the target tissue and its cells increased although the transferred fraction was small compared to the total administered plasmid DNA, ii) a transient increase in cellular translocation of plasmid DNA was induced, and iii) transcriptional factors were activated. Taking all these results into consideration, it would appear that tissue pressure-mediated transfection enhances plasmid DNA transfer to the target tissue and its cells and also activation of the transcriptional process. This information will allow a better understanding of in vivo transgene expression based on naked plasmid DNA transfection involving tissue pressure-mediated transfection.
- 日本薬学会の論文
著者
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Yamashita Fumiyoshi
Department Of Drug Delivery Research Graduate School Of Pharmaceutical Sciences Kyoto University
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Hashida Mitsuru
Department Of Basic Pharmaceutics Faculty Of Pharmaceutical Sciences Kyoto University
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Kawakami Shigeru
京都大学 薬学研究科
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Kawakami Shigeru
Dep. Of Drug Delivery Res. Graduate School Of Pharmaceutical Sciences Kyoto Univ.
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Sugahara Yazuyuki
長崎大学 医歯薬学総合研究科臨床検査医学講座
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Sugahara Yazuyuki
Dep. Of Lab. Medicine Nagasaki Univ. Graduate School Of Biomedical Sciences Nagasaki Univ. Hospital
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Kawakami Shigeru
Department Of Drug Delivery Research Graduate School Of Pharmaceutical Sciences Kyoto University
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Kohno Shigeru
長崎大学 第二内科
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Kanazawa Shigeo
公立みつぎ総合病院
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Hara Shintaro
長崎大学 医学部第二内科
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Mukai Hidefumi
Department Of Molecular Engineering Graduate School Of Engineering Kyoto University
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Sakanaka Koji
参天製薬奈良研究開発センター
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TAKAHASHI Haruyuki
Department of Physics,Faculty of Science,Niigata University
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SATAKE Kyosuke
Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University
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Kashiwagi Satsuki
School Of Pharmaceutical Sciences Nagasaki University
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Sakanaka Koji
Department Of Hospital Pharmacy Nagasaki University Hospital Of Medicine And Dentistry:santen Pharma
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Takahashi Haruyuki
Department Of Geology Ibaraki University
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Kawakami Shigeru
Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University
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Satake Kyosuke
Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University
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Takahashi Haruyuki
Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University
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