A Novel, Bio-Reducible Gene Vector Containing Arginine and Histidine Enhances Gene Transfection and Expression of Plasmid DNA
スポンサーリンク
概要
- 論文の詳細を見る
We have engineered a novel, non-viral, multifunctional gene vector (STR-CH2R4H2C) that contained stearoyl (STR) and a block peptide consisting of Cys (C), His (H), and Arg (R). STR-CH2R4H2C can form a stable nano-complex with plasmid DNA (pDNA) based on electronic interactions and disulfide cross linkages. In this study, we evaluated the efficacy of STR-CH2R4H2C as a gene vector. We first determined the optimal weight ratio for STR-CH2R4H2C/pDNA complexes. The complexes with a weight ratio of 50 showed the highest transfection efficacy. We also examined the transfection efficacy of STR-CH2R4H2C/pDNA complexes with or without serum and compared STR-CH2R4H2C/pDNA transfection efficacy with that of Lipofectamine. Even in the presence of serum, STR-CH2R4H2C showed higher transfection efficacy than did Lipofectamine. In addition, we determined the mechanism of transfection of the STR-CH2R4H2C/pDNA complexes using various cellular uptake inhibitors and evaluated its endosomal escape ability using chloroquine. Macropinocytosis was main cellular uptake pathway of STR-CH2R4H2C/pDNA complexes. Our results suggested that STR-CH2R4H2C is a promising gene delivery system.
著者
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Kanazawa Takanori
Pharmaceutics And Drug Delivery School Of Pharmacy Tokyo University Of Pharmacy And Life Science
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FUKUDA Tsunehiko
Nagahama Institute of Bio-Science and Technology
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Kanazawa Takanori
Laboratory of Pharmaceutics and Drug Delivery, Department of Pharmaceutical Science, School of Pharm
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Takashima Yuuki
Laboratory of Pharmaceutics and Drug Delivery, Department of Pharmaceutical Science, School of Pharm
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Okada Hiroaki
Laboratory of Pharmaceutics and Drug Delivery, Department of Pharmaceutical Science, School of Pharm
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Tanaka Ko
Laboratory of Pharmaceutics and Drug Delivery, Department of Pharmaceutical Science, School of Pharm
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Ogawa Takaya
Laboratory of Pharmaceutics and Drug Delivery, Department of Pharmaceutical Science, School of Pharm
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Suda Yumiko
Laboratory of Pharmaceutics and Drug Delivery, Department of Pharmaceutical Science, School of Pharm
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Fukuda Tsunehiko
Nagahama Inst. Of Bio-science And Technol.
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Okada Hiroaki
Laboratory of Pharmaceutics and Drug Delivery, Department of Pharmaceutical Science, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences
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OKADA Hiroaki
Laboratory of Applied Entomology, Faculty of Agriculture, Okayama University:(Present address)Upland Crop Pest Research Laboratory, Tohoku National Agricultural Experiment Station
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Suda Yumiko
Laboratory of Pharmaceutics and Drug Delivery, Department of Pharmaceutical Science, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences
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Kanazawa Takanori
Laboratory of Pharmaceutics and Drug Delivery, Department of Pharmaceutical Science, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences
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Takashima Yuuki
Laboratory of Pharmaceutics and Drug Delivery, Department of Pharmaceutical Science, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences
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Ogawa Takaya
Laboratory of Pharmaceutics and Drug Delivery, Department of Pharmaceutical Science, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences
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