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Extrahepatic tissue-targeted gene therapy for phenylketonuria

Research Project

Project/Area Number 20591230
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

KUME Akihiro  Jichi Medical University, 医学部, 准教授 (10264293)

Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords小児代謝 / 栄養学 / 遺伝子治療 / フェニルケトン尿症 / 先天代謝異常 / アデノ随伴ウイルス
Research Abstract

The feasibility of muscle-directed gene transfer for the treatment of phenylketonuria (PKU) was investigated. Small-sized promoters were examined for high expression in the context of self-complementary adeno-associated virus (scAAV) vector. Intramuscular injection of a scAAV encoding phenylalanine hydroxylase (PAH) did not show a significant effect in a mouse model of PKU. Simultaneous injection of three scAAV vectors encoding PAH, GTP cyclohydrolase I and 6-pyruvoil tetrahydrobiopterine synthase resulted in a significant, still moderate decrease of blood phenylalanine in PKU mice.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (26 results)

All 2011 2010 2009 2008

All Journal Article (13 results) (of which Peer Reviewed: 13 results) Presentation (13 results)

  • [Journal Article] Complete restoration of phenylalanine oxidation in phenylketonuria mouse by a self-complementary adeno-associated virus vector.2011

    • Author(s)
      Yagi H, Ogura T, Mizukami H, Urabe M, Hamada H, Yoshikawa H, Ozawa K, Kume A
    • Journal Title

      J Gene Med 13

      Pages: 114-122

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Complete restoration of phenylalanine oxidation in phenylketonuria mouse by a self-complementary adeno-associated virus vector2011

    • Author(s)
      Yagi H, et al.
    • Journal Title

      The Journal of Gene Medicine

      Volume: 13 Pages: 114-122

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A phase I study of aromatic L-amino acid decarboxylase gene therapy for Parkinson ' s disease.2010

    • Author(s)
      Muramatsu S, Fujimoto K, Kato S, Mizukami H, Asari S, Ikeguchi K, Kawakami T, Urabe M, Kume A, Sato T, Watanabe E, Ozawa K, Nakano I
    • Journal Title

      Mol Ther 18

      Pages: 1731-1735

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] A phase I study of aromatic L-amino acid decarboxylase gene therapy for Parkinson's disease2010

    • Author(s)
      Muramatsu, S, et al.
    • Journal Title

      Molecular Therapy

      Volume: 18 Pages: 1731-1735

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Systemic delivery of IL-10 by an AAV-vector presents 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 KI, Mizukami H, Kume A, Ookawara S, Ikeda U, Katayama Y, Ozawa K
    • Journal Title

      Gene Ther 16

      Pages: 383-391

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Genomic organization of regions that regulate chicken glycine decarboxylase gene transcription: Physiological and pathological conditions.2009

    • Author(s)
      Kawaguchi H, Okamoto S, Sikdar D, Kume A, Li F, Mohafez OM, Shehata MH, Hiraga K
    • Journal Title

      Gene 432

      Pages: 7-18

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Retroviral vector-producing mesenchymal stem cells for targeted suicide cancer gene therapy.2009

    • Author(s)
      Uchibori R, Okada T, Ito T, Urabe M, Mizukami H, Kume A, Ozawa K
    • Journal Title

      J Gene Med 11

      Pages: 373-381

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Kinetics and effect of integrin expression on human CD34+ cells during MLV-derived retroviral transduction with a recombinant fibronectin for stem cell gene therapy.2009

    • Author(s)
      Horiuchi Y, Onodera M, Miyagawa Y, Sato B, Onda K, Katagiri YU, Okita H, Okada M, Otsu M, Kume A, Okuyama T, Fujimoto J, Kuratsuji T, Kiyakawa N
    • Journal Title

      Hum Gene Ther 20

      Pages: 777-783

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Retroviral vector-producing mesenchymal stem cells for targeted suicide cancer gene therapy2009

    • Author(s)
      Uchibori R, et al
    • Journal Title

      J Gene Med 11

      Pages: 373-381

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Kinetics and effect of integrin expression on human CD34+ cells during MLV-derived retroviral transduction with a recombinant fibronectin for stem cell gene therapy2009

    • Author(s)
      Horiuchi Y, et al
    • Journal Title

      Hum Gene Ther 20

      Pages: 777-783

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

    • Author(s)
      Nomoto T, et al
    • Journal Title

      Gene Therapy 16

      Pages: 383-391

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Genomic organization of regions that regulate chicken glycine decarboxylase gene transcription : physiological and pathological conditions.2009

    • Author(s)
      Kawaguchi H, et al
    • Journal Title

      Gene 432

      Pages: 718-718

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

    • Author(s)
      Nonaka-Sanikawa M, et al
    • Journal Title

      Journal of Gene Medicine 10

      Pages: 368-374

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] Choice of small-sized prpmoter for AAV-mediated factor IX expression in skeletal muscle.2010

    • Author(s)
      Kume A, Yagi H, Mizukami H, Urabe M, Tsukahara T, Ishiwata A, mimuro J, Madoiwa S, Ohmori T, Sakata Y, Ozawa K
    • Organizer
      第16回日本遺伝子治療学会
    • Place of Presentation
      宇都宮
    • Year and Date
      2010-07-01
    • Related Report
      2010 Final Research Report
  • [Presentation] Promoter selection for AAV vector-mediated factor IX expression in skeletal muscle2010

    • Author(s)
      Kume A, et al.
    • Organizer
      The 13th Annual Meeting of the American Society of Gene and Cell Therapy
    • Place of Presentation
      Washington DC, USA
    • Year and Date
      2010-05-21
    • Related Report
      2010 Annual Research Report
  • [Presentation] Liver-targeted gene therapy with a self-complementary AAV ameliorates brain aminergic deficit in phenylketonuria mice.2009

    • Author(s)
      Kume A, Yagi H, Sanechika S, Ichinose H, Mizukami H, Urabe M, Ozawa K
    • Organizer
      XVIIth Annual Congress of the European Society of Gene and Cell Therapy
    • Place of Presentation
      Hannover, Germ any
    • Year and Date
      2009-11-22
    • Related Report
      2010 Final Research Report
  • [Presentation] Liver-targeted gene therapy with a self-complementary AAV ameliorates brain aminergic deficit in phenylketonuria mice2009

    • Author(s)
      Kume A, et al
    • Organizer
      XVIIth Annual Congress of the European Society of Gene and Cell Therapy
    • Place of Presentation
      Hannover, Germany
    • Year and Date
      2009-11-22
    • Related Report
      2009 Annual Research Report
  • [Presentation] Promoter selection for muscle-directed self-complementary AAV toward hemophilia B gene thearapy.2009

    • Author(s)
      Kume A, Yagi H, Mizukami H, Urabe M, Tsukahara T, Ishiwata A, Mimuro J, Madoiwa S, Ohmori T, Sakata Y, Ozawa K
    • Organizer
      第71回日本血液学会学術集会
    • Place of Presentation
      京都
    • Year and Date
      2009-10-23
    • Related Report
      2010 Final Research Report
  • [Presentation] Kinetics and defect of integrin expression on human CD34+ cells during MLV-derived retroviral transduction with a recombinant fibronectin for stem cell gene therapy.2009

    • Author(s)
      Horiuchi Y, Onodera M, Miyagawa Y, Sato B, Onda K, Katagiri YU, Okita H, Okada M, Otsu M, Kume A, Okuyaka T, Fujimoto J, Kuratsuji T, Kiyokawa N
    • Organizer
      第15回日本遺伝子治療学会
    • Place of Presentation
      吹田
    • Year and Date
      2009-07-11
    • Related Report
      2010 Final Research Report
  • [Presentation] liver-targeted gene therapy with a self-complementary AAV ameliorated brain aminergic deficit in phenylketonuria mice.2009

    • Author(s)
      Yagi H, Sanechika S, Ichinose H, Mizukami H, Ogura T, Urabe M, Hamada H, Yoshikawa K, Ozawa K, Kume A
    • Organizer
      第15回日本遺伝子治療学会
    • Place of Presentation
      吹田
    • Year and Date
      2009-07-11
    • Related Report
      2010 Final Research Report
  • [Presentation] Improvement of monoamine metabolism in phenylketonuria mouse brain treated with a self-complementary adeno-associated vector.2009

    • Author(s)
      Yagi H, Sanechika S, Ichinose H, Mizukami H, Ogura T, Urabe M, Hamada H, Yoshikawa H, Ozawa K, Kume A
    • Organizer
      American Society of Gene Therapy's 12th Annual Meeting
    • Place of Presentation
      San Diego, CA, USA
    • Year and Date
      2009-05-27
    • Related Report
      2010 Final Research Report
  • [Presentation] Promoter selection for AAV vector-mediated factor IX expression in skeletal muscle.2009

    • Author(s)
      Kume A, Yagi H, Mizukami H, Urabe M, Tsukahara T, Ishiwata A, Mimuro J, Madoiwa S, Ohmori T, Sakata Y, Ozawa K
    • Organizer
      American Society of Gene Therapy's 13th Annual Meeting
    • Place of Presentation
      Washington, DC, USA
    • Year and Date
      2009-05-21
    • Related Report
      2010 Final Research Report
  • [Presentation] 改良型アデノ随伴ウイルスベクターによるフェニルケトン尿症遺伝子治療2009

    • Author(s)
      久米晃啓、八木洋也、小倉剛、水上浩明、卜部匡司、小澤敬也
    • Organizer
      第112回日本小児科学会小児科学会学術集会
    • Place of Presentation
      奈良
    • Year and Date
      2009-04-18
    • Related Report
      2010 Final Research Report
  • [Presentation] 自己相補型アデノ随伴ウイルスベクターによるフェニルケトン尿症の遺伝子治療 ? maternal PKUの予防に向けて2009

    • Author(s)
      八木洋也、水上浩明、小倉剛、濱田洋実、吉川裕之、小澤敬也、久米晃啓
    • Organizer
      第61回日本産婦人科学会学術講演会
    • Place of Presentation
      京都
    • Year and Date
      2009-04-05
    • Related Report
      2010 Final Research Report
  • [Presentation] 筋組織を標的とするAAV ベクターを用いた「フェニルケトン尿症」に対する新生仔遺伝子治療の長期的効果2009

    • Author(s)
      小倉剛、水上浩明、八木洋也、濱田洋実、吉川裕之、小澤敬也、久米晃啓
    • Organizer
      第61回日本産婦人科学会学術講演会
    • Place of Presentation
      京都
    • Year and Date
      2009-04-05
    • Related Report
      2010 Final Research Report
  • [Presentation] Complete retoration of in vivo oxidative capacity for phenylalanine in self-complementary AAV vector-treated phenylketonuria mice.2008

    • Author(s)
      Kume A., et al
    • Organizer
      American Society of Gene Therapy 11th Annual Meeting
    • Place of Presentation
      Boston, MA, USA
    • Year and Date
      2008-05-31
    • Related Report
      2008 Annual Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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