微小技術を用いた人工染色体の細胞内移送,発現,分配の解析と操作

2009 年度 研究成果報告書

• 研究課題/領域番号: 17076013
• 研究種目: 特定領域研究
• 配分区分: 補助金
• 審査区分: 理工系
• 研究機関: 京都府立医科大学
• 研究代表者: 松田 修 京都府立医科大学, 医学研究科, 准教授 (00271164)
• 研究分担者: 今西 二郎 京都府立医科大学, 医学研究科, 教授 (40112510) ; 伏木 信次 京都府立医科大学, 医学研究科, 教授 (80150572) ; 中屋 隆明 大阪大学, 微生物病研究所, 特任准教授 (80271633)
• 研究期間 (年度): 2005 – 2009
• キーワード: 幹細胞 / 細胞情報・動態 / 遺伝子発現 / 再生医学 / サイトカイン / アレルギー / 腫瘍免疫 / エピゲノム制御

研究概要

遺伝子導入は、細胞と生体分子の機能を解析、制御する上で必須の基盤技術である。エプスタイン・バール・ウイルスのEBNA1遺伝子とoriP配列を用いると、人工染色体様の性質が発揮され、哺乳動物細胞への遺伝子導入効率と発現を著明に向上することが可能である。本研究では、マルチスケール操作によりEBNA1/oriPシステムの細胞内での局在、相互作用、複製維持等を解析するとともに、遺伝子発現制御と再生医療等への応用を行った。

研究成果

• [雑誌論文] Comparison of anti-rheumatic effects of local RNAi-based Therapy in collagen induced arthritis rats using various cytokine genes as molecular targets. (2009)
  • 著者名/発表者名: Inoue A, Takahashi KA, Mazda O, Arai Y, Saito M, Kishida T, Shin-Ya M, Morihara T, Tonomura H, Sakao K, Imanishi J, Kubo T.
  • 雑誌名: Mod Rheumatol 19 ページ: 125-133
  • 査読あり
• [雑誌論文] Interleukin-27 activates natural killer cells and suppresses NK-resistant head and neck squamous cell carcinoma through inducing antibody-dependent cellular cytotoxicity. (2009)
  • 著者名/発表者名: Matsui M, Kishida T, Nakano H, Yoshimoto K, Shin-Ya M, Shimada T, Nakai S, Imanishi J, Yoshimoto T, Hisa Y, Mazda O.
  • 雑誌名: Cancer Res 69 ページ: 2523-2530
  • 査読あり
• [雑誌論文] Intracellular enzyme-responsive fragmentation of nonviral gene carriers leads to polyplex destabilization and enhanced transgene expression. (2009)
  • 著者名/発表者名: Hashimoto T, Tachibana Y, Nozaki H, Mazda O, Niidome T, Murakami A, Yamaoka T.
  • 雑誌名: Chem Lett 38 ページ: 718-719
  • 査読あり
• [雑誌論文] Raspberry-like assembly of cross-linked nanogels for protein delivery. (2009)
  • 著者名/発表者名: Hasegawa U, Sawada SI, Shimizu T, Kishida T, Otsuji E, Mazda O, Akiyoshi K.
  • 雑誌名: J Control Release 140 ページ: 312-317
  • 査読あり
• [雑誌論文] Effects of heat stimulation via microwave applicator on cartilage matrix gene and HSP70 expression in the rabbit knee joint. (2008)
  • 著者名/発表者名: Tonomura H, Takahashi KA, Mazda O, Arai Y, Shin-Ya M, Inoue A, Honjo K, Hojo T, Imanishi J, Kubo T.
  • 雑誌名: J Orthop Res 26 ページ: 34-41
  • 査読あり
• [雑誌論文] Pleiotrophic functions of Epstein-Barr virus nuclear antigen-1 (EBNA-1) and oriP differentially contribute to the efficacy of transfection/expression of exogenous gene in mammalian cells. (2008)
  • 著者名/発表者名: Kishida T, Asada H, Kubo K, Sato Y, Shin-Ya M, Imanishi J, Yoshikawa K, Mazda O.
  • 雑誌名: J Biotechnol 133 ページ: 201-207
  • 査読あり
• [雑誌論文] Nanogel DDS enables sustained release of IL-12 for tumor immunotherapy. (2008)
  • 著者名/発表者名: Shimizu T, Kishida T, Hasegawa U, Ueda Y, Imanishi J, Yamagishi H, Akiyoshi K, Otsuji E, Mazda O.
  • 雑誌名: Biochem Biophys Res Commun 367 ページ: 330-335
  • 査読あり
• [雑誌論文] Therapeutic RNA interference of malignant melanoma by electrotransfer of small interfering RNA targeting Mitf. (2007)
  • 著者名/発表者名: Nakai N, Kishida T, Shin-Ya M, Imanishi J, Ueda Y, Kishimoto S, Mazda O.
  • 雑誌名: Gene Ther 14 ページ: 357-365
  • 査読あり
• [雑誌論文] Sono- poration-mediated transduction of pDNA/siRNA into joint synovium in vivo. (2007)
  • 著者名/発表者名: Saito M, Mazda O, Takahashi KA, Arai Y, Kishida T, Shin-Ya M, Inoue A, Tonomura H, Sakao K, Morihara T, Imanishi J, Kawata M, Kubo T.
  • 雑誌名: J Orthop Res 25 ページ: 1308-1316
  • 査読あり
• [雑誌論文] IL-21 administration into the nostril alleviates murine allergic rhinitis. (2007)
  • 著者名/発表者名: Hiromura Y, Kishida T, Nakano H, Hama T, Imanishi J, Hisa Y, Mazda O.
  • 雑誌名: J Immunol 179 ページ: 7157-7165
  • 査読あり
• [雑誌論文] IL-21 induces inhibitor of differentiation 2 (Id2) and leads to complete abrogation of anaphylaxis in mice. (2007)
  • 著者名/発表者名: Kishida T, Hiromura Y, Shin-Ya M, Asada H, Kuriyama H, Sugai M, Shimizu A, Yokota Y, Hama T, Imanishi J, Hisa Y, Mazda O.
  • 雑誌名: J Immunol 179 ページ: 8554-8561
  • 査読あり
• [雑誌論文] Interleukin-21 triggers both cellular and humoral immune responses leading to therapeutic antitumor effects against head and neck squamous cell carcinoma. (2006)
  • 著者名/発表者名: Nakano H, Kishida T, Asada H, Shin-Ya M, Shinomiya T, Imanishi J, Shimada T, Nakai S, Takeuchi M, Hisa Y, Mazda O.
  • 雑誌名: J Gene Med 8 ページ: 90-99
  • 査読あり
• [雑誌論文] Transthoracic direct current (DC) shock facilitates intramyocardial transfection of naked plasmid DNA infused via coronary vessels in canines. (2006)
  • 著者名/発表者名: Iida Y, Oda Y, Nakamori S, Tsunoda S, Kishida T, Gojo S, Shin-Ya M, Asada H, Imanishi J, Yoshikawa T, Matsubara H, Mazda O.
  • 雑誌名: Gene Ther 13 ページ: 906-916
  • 査読あり
• [雑誌論文] In vivo gene therapy of type I diabetic mellitus using a cationic emulsion containing an Epstein Barr virus (EBV) based plasmid vector. (2006)
  • 著者名/発表者名: Yoo HS, Mazda O, Lee HY, Kim JC, Kwon SM, Lee JE, Kwon IC, Jeong H, Jeong YS, Jeong SY.
  • 雑誌名: J Control Release 112 ページ: 139-144
  • 査読あり
• [雑誌論文] Intracellular interferon triggers Jak/Stat signaling cascade and induces p53-dependent antiviral protection. (2005)
  • 著者名/発表者名: Shin-Ya M, Hirai H, Satoh E, Kishida T, Asada H, Aoki F, Tsukamoto M, Imanishi J, Mazda O.
  • 雑誌名: Biochem Biophys Res Commun 329 ページ: 1139-1146
  • 査読あり
• [雑誌論文] Yoshikawa K. Folding transition into a loosely collapsed state in plasmid DNA as revealed by single-molecule observation. (2005)
  • 著者名/発表者名: Sato YT, Hamada T, Kubo K, Yamada A, Kishida T, Mazda O
  • 雑誌名: FEBS Lett 579 ページ: 3095-3099
  • 査読あり
• [雑誌論文] Sonoporation using microbubble BR14 promotes pDNA/siRNA transduction to murine heart. (2005)
  • 著者名/発表者名: Tsunoda S, Mazda O, Oda Y, Iida Y, Akabame S, Kishida T, Shin-Ya M, Asada H, Gojo S, Imanishi J, Matsubara H, Yoshikawa T.
  • 雑誌名: Biochem Biophys Res Commun 336 ページ: 118-127
  • 査読あり
• [雑誌論文] Electrotransfer of small interfering RNA ameliorated arthritis in rats. (2005)
  • 著者名/発表者名: Inoue A, Takahashi KA, Mazda O, Terauchi R, Arai Y, Kishida T, Shin-Ya M, Asada H, Morihara T, Tonomura H, Ohashi S, Kajikawa Y, Kawahito Y, Imanishi J, Kawata M, Kubo T.
  • 雑誌名: Biochem Biophys Res Commun 336 ページ: 903-908
  • 査読あり
• [雑誌論文] Mitf silencing cooperates with IL-12 gene transfer to inhibit melanoma in mice.
  • 著者名/発表者名: Nakai N, Kishida T, Hartmann G, Katoh N, Imanishi J, Kishimoto S, Mazda O.
  • 雑誌名: Int Immunopharmacol (in press)
  • 査読あり
• [学会発表] The Epstein-Barr virus-based episomal vectors may provide efficient means of genetic transduction in vitro and in vivo. (2009)
  • 著者名/発表者名: Mazda O, Kishida T, Imanishi J.
  • 学会等名: 2nd World Congress of Regenerative Medicine & Stem Cell-2009 (RMSC-2009)/4th China Medical Biotech Forum (CMBF)
  • 発表場所: Dalian, China
  • 年月日: 20090808-20090810
• [学会発表] A strain of unicellular alga that may provide a novel functional food to decelerate senescence. (2009)
  • 著者名/発表者名: Kishida T, Imanishi J, Mazda O.
  • 学会等名: 3rd FEMS Congress of European Microbiologists.
  • 発表場所: Gothenberg, Sweden
  • 年月日: 20090628-20090702
• [学会発表] Infectious capability of HSV-1 is drastically reduced by high pressure-based procedures to attenuate virus. (2009)
  • 著者名/発表者名: Cui FD, Kishida T, Imanishi J, Hayakawa K, Mazda O.
  • 学会等名: 3rd FEMS Congress of European Microbiologists.
  • 発表場所: Gothenberg, Sweden
  • 年月日: 20090628-20090702
• [学会発表] Multiple functions and subcellular localization of EBV nuclear antigen-1 (EBNA-1) contributes to transfection/ 6 expression efficiencies of EBV episomal vectors in mammalian cells. (2009)
  • 著者名/発表者名: Mazda O, Kishida T, Asada H, Yoshimura SH, Imanishi J.
  • 学会等名: 3rd FEMS Congress of European Microbiologists.
  • 発表場所: Gothenberg, Sweden
  • 年月日: 20090628-20090702
• [学会発表] Local administration of IL-21 suppresses nasal allergic reaction in a murine model. (2009)
  • 著者名/発表者名: Hiromura Y, Mazda O, Kishida T, Hama T, Hisa Y.
  • 学会等名: The 29th Annual Midwinter Research Meeting of the Association for Research in Otolaryngology (ARO)
  • 発表場所: Baltimore, MD, USA
  • 年月日: 2009-02-05
• [学会発表] IL-21 administration into the nostril alleviates murine allergic rhinitis. (2008)
  • 著者名/発表者名: Hiromura Y, Kishida T, Nakano H, Hama T, Mazda O, Hisa Y.
  • 学会等名: The 12th Japan-Korean joint meeting of Otorhinolaryngology-Head and Neck Surgery.
  • 発表場所: Nara
  • 年月日: 2008-04-05
• [学会発表] Cationic silica nanoparticles efficiently transfer into mammalian cells. (2007)
  • 著者名/発表者名: Li L, Takenaka T, Zinchenko AA, Chen N, Inagaki S, Asada H, Kishida T, Mazda O, Murata S, Yoshikawa K.
  • 学会等名: 2007 International Symposium on Micro-NanoMechatronics and Human Science
  • 発表場所: Nagoya
  • 年月日: 20071112-20071113
• [学会発表] IL-27 induced antitumor effects against HNSCC in mice. (2007)
  • 著者名/発表者名: Matsui M, Kishida T, Asada H, Nakano H, Imanishi J, Mazda O, Hisa Y.
  • 学会等名: AAO-HNSF 2007 Annual Meeting & OTO EXPO.
  • 発表場所: Washington DC, USA
  • 年月日: 20070916-20070919
• [学会発表] The therapeutic effects of inflammatory cytokine-specific small interfering RNA transduction into joints on rat arthritis. (2007)
  • 著者名/発表者名: Inoue A, Takahashi KA, Arai Y, Saito M, Tonomura H, Sakao K, Mazda O, Imanishi J, Kubo T.
  • 学会等名: 53rd Annual Meeting of the Orthopaedic Research Society.
  • 発表場所: San Diego, CA, USA
  • 年月日: 20070211-20070214
• [学会発表] Synergistic effect of both TRAIL gene and a low dose of anti-cancer drugs on liver metastasis. (2007)
  • 著者名/発表者名: Iwai M, Ishii M, Harada Y, Mori T, Itoh Y, Okanoue T, Kishida T, Mazda O, Imanishi J.
  • 学会等名: 17th Asian Pacific Association for the Study of the Liver (APASL)
  • 発表場所: Kyoto, Japan
  • 年月日: 2007-03-29
• [学会発表] Local administration of IL-21 suppresses nasal allergic reaction in a murine model. (2006)
  • 著者名/発表者名: Hiromura Y, Mazda O, Kishida T, Hama T, Hisa Y.
  • 学会等名: 1st Joint Meeting of European National Societies of Immunology and 16th European Congress of Immunology.
  • 発表場所: Paris, France
  • 年月日: 2006-02-07
• [学会発表] EBV-based artificial chromosome provides an efficient tool for gene delivery into mammalian cells. (2005)
  • 著者名/発表者名: Kishida T, Imanishi J, Mazda O.
  • 学会等名: NanoBio Europe 2005
  • 発表場所: Muenster, Germany.
  • 年月日: 20050922-20050924
• [図書] Front Biosci(Molecular therapeutics of cancer by means of electroporation-based transfer of siRNAs and EBV-based expression vectors.) (2009)
  • 著者名/発表者名: Mazda O, Kishida T.
  • 総ページ数: 316-331
• [図書] Nonviral gene administration by means of the EBV-based episomal vectors and it application to gene therapy and regenerative medicine.(Summarized Report of Symposium on"System Cell Engineering by Multi-scale manipulation" at 20th Anniversary MHS2009 & Micro-Nano Global) (2009)
  • 著者名/発表者名: Mazda O, Kishida T, Matsui M, Nakano H, Yoshimoto K, Shimada T, Nakai S, Imanishi J, Hisa Y.
  • 総ページ数: 21-26
  • 出版者: COE
• [図書] Subcellular localization of EBNA1 and oriP that may support the high rate of exogenous gene transfer achieved using the EBV genetic elements.(Proceedings of the 2008 International Symposium on Micro-Nano Mechatronics and Human Science,) (2008)
  • 著者名/発表者名: Asada H, Yoshimura SH, Kishida T, Imanishi J, Mazda O.
  • 総ページ数: 54-59
  • 出版者: MHS
• [図書] Cationic silica nanoparticles are efficiently transferred into mammalian cells.(2007 International Symposium on Micro-Nano Mechatronics and Human Science,) (2007)
  • 著者名/発表者名: Liu L, Takenaka T, Zinchenko AA, Chen N, Inagaki S, Asada H, Kishida T, Mazda O, Murata S, Yoshikawa, K.
  • 総ページ数: 281-285
  • 出版者: MHS
• [図書] Interleukin-21 as an effective suppressant for IgE-mediated allergic hypersensitivity reactions.(2007 International Symposium on Micro-Nano Mechatronics and Human Science,) (2007)
  • 著者名/発表者名: Kishida T, Hiromura Y, Hama T, Imanishi J, Hisa Y, Mazda O.
  • 総ページ数: 304-309
  • 出版者: MHS
• [図書] Gene Therapy 2007.(Ochiai T, Shimada H, Tagawa M, editors., Electroporation-mediated molecular therapeutics of cancer using short interfering RNA and EBV-based DNA construct with properties of an artificial chromosome.) (2007)
  • 著者名/発表者名: Mazda O, Kishida T.
  • 総ページ数: 34-55
  • 出版者: Medical View
• [図書] Novel gene transduction procedures in vivo using the Epstein-Barr virus-based artificial chromosomes.(2006 IEEE International Symposium on Micro-Nano Mechatronics and Human Science,) (2006)
  • 著者名/発表者名: Mazda O, Kishida T, Asada H, Iida Y, Tsunoda S, Oda Y, Shin-Ya M, Yoshikawa T, Matsubara H, Imanishi J.
  • 総ページ数: 22-27
  • 出版者: MHS
• [図書] Non-viral gene therapy: gene design and delivery.(Taira K, Kataoka K, Niidome T, editors., Functional Nucleotide sequences capable of promoting nonviral genetic transfer.) (2005)
  • 著者名/発表者名: Mazda O, Kishida T.
  • 総ページ数: 198-210
  • 出版者: Springer-Verlag
• [図書] Application of EBV-based artificial chromosome to genetic engineering of mammalian cells and tissues.(Proceedings of the 2005 International Symposium on Micro-NanoMechatronics and Human Science, Eighth Symposium on Micro- and Nano-Mechatronics for Information-Based Society - The 21st Century) (2005)
  • 著者名/発表者名: Kishida T, Shin-Ya M, Imanishi J, Mazda O.
  • 総ページ数: 124-129
  • 出版者: COE Progr