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Tissue specificity and utility of AAV vectors in hemophilia gene therapy

Research Project

Project/Area Number 19591134
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionJichi Medical University

Principal Investigator

MIZUKAMI Hiroaki  Jichi Medical University, 医学部, 講師 (20311938)

Project Period (FY) 2007 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2008: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2007: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords遺伝子治療 / AAV ベクター / 組織特異性 / 免疫応答 / トランスジェニックマウス / 中和抗体 / AAVベクター / トランスジェニックスマウス
Research Abstract

様々な血清型に由来するAAV ベクターの組織特異性に関する検討を行った結果、骨格筋に対しては1型のベクターにCMV プロモーターを用いた場合が、肝臓には8型のベクターにhAAT プロモーターを用いるのが最も有効との結論を得た。また、in vivo のベクター投与において問題となる中和抗体検出系に関して検出方法・反応方法などの関連条件を検討することで、検出感度を著明に改善させることができた。

Report

(3 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • Research Products

    (46 results)

All 2009 2008 2007

All Journal Article (16 results) (of which Peer Reviewed: 16 results) Presentation (29 results) Book (1 results)

  • [Journal Article] Systemic delivery of IL-10 by an AAV vector prevents vascular remodeling and end-organ damage in stroke-prone spontaneously hypertensive rat.2009

    • Author(s)
      Nomoto, T., Okada, T., Shimazaki, K., Yoshioka, T., Nonaka-Sarukawa, M., Ito, T., Takeuchi, K., Katsura, K., Mizukami, H., Kume, A., Ookawara, S., Ikeda, U., Katayama, Y., Ozawa, K.
    • Journal Title

      Gene Ther 16

      Pages: 383-91

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Systemic delivery of IL-10 by an AAV vector prevents vascular remodeling and end-organ damage in stroke-prone spontaneously hypertensive rat.2009

    • Author(s)
      Nomoto T
    • Journal Title

      Gene Therapy 16

      Pages: 383-391

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Overexpression of PTEN in ovarian cancer cells suppresses i.p. dissemination and extends survival in mice.2008

    • Author(s)
      Takei, Y., Saga, Y., Mizukami, H., Takayama, T., Ohwada, M., Ozawa, K., Suzuki, M.
    • Journal Title

      Mol Cancer Ther 7

      Pages: 704-11

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Adeno-associated virus vector-mediated systemic interleukin-10 expression ameliorates hypertensive organ damage in Dahl salt-sensitive rats.2008

    • Author(s)
      Nonaka-Sarukawa, M., Okada, T., Ito, T., Yamamoto, K., Yoshioka, T., Nomoto, T., Hojo, Y., Shimpo, M., Urabe, M., Mizukami, H., Kume, A., Ikeda, U., Shimada, K., Ozawa, K.
    • Journal Title

      J Gene Med 10

      Pages: 368-74

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Adeno-associated virus vector-mediated production of hepatocyte growth factor attenuates liver fibrosis in mice.2008

    • Author(s)
      Suzumura, K., Hirano, T., Son, G., Iimuro, Y., Mizukami, H., Ozawa, K., Fujimoto, J.
    • Journal Title

      Hepatol Int 2

      Pages: 80-88

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Protection Against Aminoglycoside-induced Ototoxicity by Regulated AAV Vector-mediated GDNF Gene Transfer Into the Cochlea.2008

    • Author(s)
      Liu, Y., Okada, T., Shimazaki, K., Sheykholeslami, K., Nomoto, T., Muramatsu, SI., Mizukami, H., Kume, A., Xiao, S., Ichimura, K., Ozawa, K.
    • Journal Title

      Mol Ther 16

      Pages: 474-80

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Overexpression of PTEN in ovarian cancer cells suppresses i. p. dissemination and extends survival in mice.2008

    • Author(s)
      Takei Y
    • Journal Title

      Molecular Cancer Therapy 7

      Pages: 704-11

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Adeno-associated virus vector-mediated production of hepatocyte growth factor attenuates liver fibrosis in mice.2008

    • Author(s)
      Suzumura K
    • Journal Title

      Hepatology International 2

      Pages: 80-88

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Overexpression of PTEN in ovarian cancer cells suppresses i.p. dissemination and extends survival in mice2008

    • Author(s)
      Takei Y, et. al.
    • Journal Title

      Mol Cancer Ther 7

      Pages: 704-11

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Interleukin-10 expression mediated by an adeno-associated virus vector prevents monocrotaline-induced pulmonary arterial hypertension in rats.2007

    • Author(s)
      Ito, T., Okada, T., Miyashita, H., Nomoto, T., Nonaka-Sarukawa, M., Uchibori, R., Maeda, Y., Urabe, M., Mizukami, H., Kume, A., Takahashi, M., Ikeda, U., Shimada, K., Ozawa, K.
    • Journal Title

      Circ Res 101

      Pages: 734-41

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Adenoassociated virus-mediated prostacyclin synthase expression prevents pulmonary arterial hypertension in rats.2007

    • Author(s)
      Ito, T., Okada, T., Mimuro, J., Miyashita, H., Uchibori, R., Urabe, M., Mizukami, H., Kume, A., Takahashi, M., Ikeda, U., Sakata, Y., Shimada, K., Ozawa, K.
    • Journal Title

      Hypertension 50

      Pages: 531-6

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Prevention of diabetic retinopathy by intraocular soluble flt-1 gene transfer in a spontaneously diabetic rat model.2007

    • Author(s)
      Ideno, J., Mizukami, H., Kakehashi, A., Saito, Y., Okada, T., Urabe, M., Kume, A., Kuroki, M., Kawakami, M., Ishibashi, S., and Ozawa, K.
    • Journal Title

      Int J Mol Med 19

      Pages: 75-9

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Suppression of ovarian cancer by muscle-mediated expression of soluble VEGFR-1/Flt-1 using adeno-associated virus serotype 1-derived vector.2007

    • Author(s)
      Takei, Y., Mizukami, H., Saga, Y., Yoshimura, I., Hasumi, Y., Takayama, T., Kohno, T., Matsushita, T., Okada, T., Kume, A., Suzuki, M., Ozawa, K.
    • Journal Title

      Int J Cancer 120

      Pages: 27-84

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Tendon healing in vitro: Adeno-associated virus-2 effectively transduces intrasynovial tenocytes with persistent expression of the transgene, but other serotypes do not.2007

    • Author(s)
      Wang, X.T., Liu, P.Y., Tang, J.B., Mizukami, H., Xin, KQ., Ozawa, K., Ushijima, H.
    • Journal Title

      Plast Reconstr Surg 119

      Pages: 227-34

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Interleukin-10 expression mediated by an adeno-associated virus vector prevents monocrotaline-induced pulmonary arterial hypertension in rats.2007

    • Author(s)
      Ito T, et. al.
    • Journal Title

      Circulation Research 101

      Pages: 734-41

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Adenoassociated virus-mediated prostacyclin synthase expression prevents pulmonary arterial hypertension in rats 50:,2007.2007

    • Author(s)
      Ito T, et. al.
    • Journal Title

      Hypertension 50

      Pages: 531-6

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] 遺伝子治療の現状と課題2008

    • Author(s)
      水上浩明、小澤敬也
    • Organizer
      第28 回 医療情報学連合大会
    • Place of Presentation
      オーガナイズドセッション「ゲノムインフォマティクス」横浜
    • Year and Date
      2008-11-23
    • Related Report
      2008 Final Research Report
  • [Presentation] Therapeutic efficacy of AAV vectors encoding sflt-4 against endometrial cancer model with lymph node metastasis.2008

    • Author(s)
      Takahashi K, Mizukami H, Saga Y, Takei Y, Urabe M, Kume A, Suzuki M, Ozawa K
    • Organizer
      The 67^<th> annual meeting of the Japanese Cancer Association(EW11-2, Abstract p495)
    • Place of Presentation
      Nagoya
    • Year and Date
      2008-10-28
    • Related Report
      2008 Final Research Report
  • [Presentation] Role of inflammatory cytokines in tumor tropism of mesenchimal stromal cells.2008

    • Author(s)
      Uchibori R, Ito T, Mizuguchi H, Urabe M, Mizukami H, Kume A, Ozawa K
    • Organizer
      The 67^<th> annual meeting of the Japanese Cancer Association(O-369, Abstract p300)
    • Place of Presentation
      Nagoya
    • Year and Date
      2008-10-27
    • Related Report
      2008 Final Research Report
  • [Presentation] Inhibitory actions of very low titer neutralizing antibody against AAV8 capsid upon transgene expression in monkey.2008

    • Author(s)
      Mizukami H, Urabe M, Kume A, Ozawa K
    • Organizer
      The 67^<th> annual meeting of the Japanese Cancer Association(O-162, Abstract p91)
    • Place of Presentation
      Nagoya
    • Year and Date
      2008-10-26
    • Related Report
      2008 Final Research Report
  • [Presentation] AAV に対する中和抗体の遺伝子導入に及ぼす影響・カニクイザルにおける検討2008

    • Author(s)
      水上浩明、八木洋也、卜部匡司、久米晃啓、小澤敬也
    • Organizer
      第56 回日本ウイルス学会学術集会(抄録集p229)
    • Place of Presentation
      岡山
    • Year and Date
      2008-10-26
    • Related Report
      2008 Final Research Report
  • [Presentation] AAVベクターを用いた遺伝子導入法と免疫反応-血友病Bに関する検討を中心に2008

    • Author(s)
      水上浩明
    • Organizer
      第70回日本血液学会総会
    • Place of Presentation
      京都
    • Year and Date
      2008-10-10
    • Related Report
      2008 Annual Research Report
  • [Presentation] Inhibitory actions of very low titer neutralizing antibody against AAV8 capsid upon liver-mediated factor IX expression in non-human primates2008

    • Author(s)
      Mizukami H, Mimuro J, Ishiwata A, Ono F, Yagi H, Urabe M, Ito T, Kume A, Terao K, Yasutomi Y, Sakata Y, Ozawa K.
    • Organizer
      The 14^<th> Annual Meeting of Japan Society of Gene Therapy(Abstract #65)
    • Place of Presentation
      Sapporo
    • Year and Date
      2008-06-14
    • Related Report
      2008 Final Research Report
  • [Presentation] Full reconstitution of in vivo oxidative activity for phenylalanine in self-complementary AAV vector-treated phenylketonuria mice.2008

    • Author(s)
      Kume A, Yagi H, Mizukami H, Urabe M, Ito T, Ozawa, K.
    • Organizer
      The 14^<th> Annual Meeting of Japan Society of Gene Therapy(Abstract #70)
    • Place of Presentation
      Sapporo
    • Year and Date
      2008-06-14
    • Related Report
      2008 Final Research Report
  • [Presentation] Establishment of a lymph node metastasis model with endometrial cancer and therapeutic efficacy of AAV vectors encoding sflt-4.2008

    • Author(s)
      Takahashi, T., Mizukami, H., Saga, Y., Takei, Y., Urabe, M., Kume, A., Suzuki, M., Ozawa, K.
    • Organizer
      The 14^<th> Annual Meeting of Japan Society of Gene Therapy(Abstract #74)
    • Place of Presentation
      Sapporo
    • Year and Date
      2008-06-14
    • Related Report
      2008 Final Research Report
  • [Presentation] Immune responses in gene herapy using adeno-associated vectors2008

    • Author(s)
      Mizukami, H.
    • Organizer
      Educational seminar IV "AAV vectors" The 14^<th> Annual Meeting of Japan Society of Gene Therapy
    • Place of Presentation
      Sapporo
    • Year and Date
      2008-06-13
    • Related Report
      2008 Final Research Report
  • [Presentation] Unexpected silencing of transgene integrated at AAVS1 locus using AAV machinary.2008

    • Author(s)
      Obara Y, Urabe M, Ito T, Mizukami H, Kume A, Ozawa K.
    • Organizer
      The 14^<th> Annual Meeting of Japan Society of Gene Therapy(Abstract #11)
    • Place of Presentation
      Sapporo
    • Year and Date
      2008-06-13
    • Related Report
      2008 Final Research Report
  • [Presentation] AAV vector-mediated systemic interleukin-10 expression ameliorates the metabolic syndrome in Zucker fatty rats.2008

    • Author(s)
      Ito T, Nakata M, Uchibori R, Urabe M, Mizukami H, Kume A, Yada T, Shimada K, Ozawa K.
    • Organizer
      The 14^<th> Annual Meeting of Japan Society of Gene Therapy(Abstract #32)
    • Place of Presentation
      Sapporo
    • Year and Date
      2008-06-13
    • Related Report
      2008 Final Research Report
  • [Presentation] “Immune responses in gene therapy using adeno-associated vectors"Educational seminar IV, “AAV vectors".2008

    • Author(s)
      Mizukami H
    • Organizer
      The 14^<th> Annual Meeting of Japan Society of Gene Therapy
    • Place of Presentation
      札幌
    • Year and Date
      2008-06-13
    • Related Report
      2008 Annual Research Report
  • [Presentation] Aromatic L-amino acid decarboxylase gene transfer for parkinson's disease: preliminary results of an open-label safety study.2008

    • Author(s)
      Muramatsu S, Fujimoto K, Kato S, Mizukami H, Ikeguchi K, Kawakami T, Urabe M, Kume A, Sato T, Watanabe E, Ozawa K, Nakano I.
    • Organizer
      The 14^<th> Annual Meeting of Japan Society of Gene Therapy(Abstract #4)
    • Place of Presentation
      Sapporo
    • Year and Date
      2008-06-12
    • Related Report
      2008 Final Research Report
  • [Presentation] Liver-mediated factor IX expression and neutralizing antibody in non-human primates.2008

    • Author(s)
      Mizukami H
    • Organizer
      The 11^<th> Annual Meeting of American Society of Gene Therapy
    • Place of Presentation
      Boston, USA
    • Year and Date
      2008-05-29
    • Related Report
      2008 Annual Research Report
  • [Presentation] 「AAV ベクターを用いた遺伝子治療の現状と展望」自治医科大学21 世紀COE プログラム2008

    • Author(s)
      水上浩明、小澤敬也
    • Organizer
      第5回合同シンポジウム
    • Place of Presentation
      自治医科大学
    • Year and Date
      2008-02-02
    • Related Report
      2008 Final Research Report
  • [Presentation] 間葉系幹細胞と造血幹細胞の相互作用の分子メカニズム2008

    • Author(s)
      菊池裕二、久米晃啓、卜部匡司、水上浩明、鈴木隆浩、尾崎勝俊、小澤敬也
    • Organizer
      第6回幹細胞シンポジウム
    • Place of Presentation
      東京
    • Related Report
      2008 Final Research Report
  • [Presentation] カニクイザルを用いたAAV ベクターの有効性評価2007

    • Author(s)
      水上浩明
    • Organizer
      第3回霊長類医科学フォーラム
    • Place of Presentation
      つくば
    • Year and Date
      2007-12-06
    • Related Report
      2008 Final Research Report
  • [Presentation] Low seropositivity against AAV serotypes 1,8 and 9 in specific pathogen-free cynomolgus monkey colony2007

    • Author(s)
      Mizukami H, et. al.
    • Organizer
      European Society for Gene and Cell Therapy
    • Place of Presentation
      Rotterdam,Netherland
    • Year and Date
      2007-10-29
    • Related Report
      2007 Annual Research Report
  • [Presentation] "AAV-mediated gene transfer: current status and future perspectives" The department of Microbiology2007

    • Author(s)
      Mizukami, H.
    • Organizer
      Molecular Genetics and Immunology Seminar Series
    • Place of Presentation
      The University of Kansas Medical Center, Kansas City (USA)
    • Year and Date
      2007-05-29
    • Related Report
      2008 Final Research Report
  • [Presentation] 肝臓特異的にFVIII を高発現するAAV8 ベクターを用いた血友病A マウスへのFVIII 遺伝子導入2007

    • Author(s)
      石渡彰、三室淳、柏倉裕志、大森司、諏合輝子、窓岩清治、水上浩明、久米晃啓、小澤敬也、坂田洋一
    • Organizer
      第30 回日本血栓止血学会総会(抄録集p462)
    • Place of Presentation
      志摩
    • Related Report
      2008 Final Research Report
  • [Presentation] 血友病B 遺伝子治療の非ヒト霊長類モデルにおける基礎的検討2007

    • Author(s)
      石渡彰、三室淳、水上浩明、小野文子、柏倉裕志、大森司、諏合輝子、窓岩清治、寺尾恵治、小澤敬也、坂田洋一
    • Organizer
      第69 回日本血液学会総会・第49 回日本臨床血液学会合同総会(抄録集p190)
    • Place of Presentation
      横浜
    • Related Report
      2008 Final Research Report
  • [Presentation] Sustained expression of prostacyclin synthase by an intramuscular injection of an AAV vector attenuates obesity in Zucker fatty rats.2007

    • Author(s)
      Ito, T., Okada, T., Mimuro, J., Nakata, M., Uchibori, R., Urabe, M., Mizukami, H., Kume, A., Sakata, Y., Yada, T., Shimada, K., Ozawa, K.
    • Organizer
      The 13th Annual Meeting of Japan Society of Gene Therapy(Abstract #092)
    • Place of Presentation
      Nagoya
    • Related Report
      2008 Final Research Report
  • [Presentation] Efficient and stable liver transduction by a self-complementary adeno-associated virus vector for phenylketonuria gene therapy.2007

    • Author(s)
      Kume, A., Matsushita, T., Mizukami, H., Urabe, M., Okada T., Ozawa, K.
    • Organizer
      The 13th Annual Meeting of Japan Society of Gene Therapy(J Gene Med 10:443-444, 2008)
    • Place of Presentation
      Nagoya
    • Related Report
      2008 Final Research Report
  • [Presentation] Prevalence of neutralizing antibody against AAV serotypes 1, 8 and 9 in cynomolgus monkey colonies.2007

    • Author(s)
      Mizukami, H., Ishiwata, A., Ono, F., Takano, J., Fujimoto, K., Mimuro, J., Urabe, M., Kume, A., Terao, K., Sakata, Y., Ozawa, K.
    • Organizer
      The 13th Annual Meeting of Japan Society of Gene Therapy(J Gene Med 10:453, 2008)
    • Place of Presentation
      Nagoya
    • Related Report
      2008 Final Research Report
  • [Presentation] Safety of intracranial AAV vector injection in cynomolgus monkeys.2007

    • Author(s)
      Mizukami, H., Muramatsu, S., Ono, F., Mimuro, J., Sakata, Y., Urabe, M., Kume, A., Tera,o K., Nakano, I., Ozawa, K.
    • Organizer
      The 13th Annual Meeting of Japan Society of Gene Therapy(J Gene Med 10:454, 2008)
    • Place of Presentation
      Nagoya
    • Related Report
      2008 Final Research Report
  • [Presentation] Overexpression of PTEN in ovarian cancer cells suppresses peritoneal dissemination and extends survival in mice.2007

    • Author(s)
      Takei, Y., Saga, Y., Mizukami, H., Ozawa, K., Suzuki, M.
    • Organizer
      The 66th Annual Meeting of the Japanese Cancer Association2007.(Proceedings of the 66th Annual Meeting of the Japanese Cancer Association, p245)
    • Place of Presentation
      Yokohama
    • Related Report
      2008 Final Research Report
  • [Presentation] Tumor tracking and therapeutic gene amplification by using retroviral vector-producing Mesenchymal stem cells for reinforcement of suicide cancer gene therapy.2007

    • Author(s)
      Uchibori, R., Okada, T., Ito, T., Matsushita, T., Urabe, M., Mizukami, H., Kume, A., Ozawa, K.
    • Organizer
      The 13th Annual Meeting of Japan Society of Gene Therapy(J Gene Med 10:478-479, 2008)
    • Place of Presentation
      Nagoya
    • Related Report
      2008 Final Research Report
  • [Presentation] Production of more potent type 1 adeno-associated virus vectors in insect cells.2007

    • Author(s)
      Urabe, M., Mizukami, H., Bakker, A., Kume, A., Hermens, W., Ozawa, K.
    • Organizer
      The 13th Annual Meeting of Japan Society of Gene Therapy(Abstract #010)
    • Place of Presentation
      Nagoya
    • Related Report
      2008 Final Research Report
  • [Book] 『糖尿病学-基礎と臨床』2007

    • Author(s)
      水上 浩明(分担執筆)
    • Total Pages
      1200
    • Publisher
      西村書店
    • Related Report
      2007 Annual Research Report

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Published: 2007-04-01   Modified: 2016-04-21  

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