Multi-scale manipulation-based analyses and application of the artificial chromosome-like characteristics of the Epstein-Barr virus-based episomal vectors

2009 Fiscal Year Final Research Report

• Project/Area Number: 17076013
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Science and Engineering
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: MAZDA Osam Kyoto Prefectural University of Medicine, 医学研究科, 准教授 (00271164)
• Co-Investigator(Kenkyū-buntansha): IMANISHI Jiro 京都府立医科大学, 医学研究科, 教授 (40112510) ; FUSHIKI Shinnji 京都府立医科大学, 医学研究科, 教授 (80150572) ; NAKAYA Takaaki 大阪大学, 微生物病研究所, 特任准教授 (80271633)
• Project Period (FY): 2005 – 2009
• Keywords: 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

Research Abstract

Gene transfection provides a fundamental technology to analyze, estimate and manipulate cellular and biomolecular functions. The Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) gene and oriP sequence offer characteristics of an artificial chromosome, drastically improving transduction rate as well as expression level in mammalian cells. Using multiscale manipulation technologies, we analyzed intracellular localization, interaction, replication and maintenance of EBNA1/oriP in living cells, and applied them to regulation of gene expression as well as to regenerative medicine.

Research Products

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