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Development of multifunctional vectors

Research Project

Project/Area Number 17550159
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Chemistry related to living body
Research InstitutionOsaka City University

Principal Investigator

NAGASAKI Takeshi  Osaka City University, Graduate School of Engineering, Associate Professor, 大学院工学研究科, 助教授 (30237507)

Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2005: ¥2,800,000 (Direct Cost: ¥2,800,000)
KeywordsBiomaterials / Nano-biotechnology / Gene / Biotechnology / Gene delivery / Non-viral vector / Transfection / Cell biology / 非ウイルスベクター / 生体機能利用 / 細胞内動態 / エンドサイトーシス
Research Abstract

The effective gene delivery system is an essential element for successful achievement of not only the gene therapy but also exhaustive analyses of genes at post-genome era. The non-viral vector has to act as a molecular machinery like a virus infecting into host cells and amplifying efficiently in order to overcome extracellular and intracellular barriers and has to lead a smooth mRNA transcription at nuclei as a final destination. In this project, stimulus responsive gene delivery systems in which some structural factors and/or physiological properties are regulated responding extracellular signals such as light are developed as a new generation of non-viral vectors. In order to enhance the nuclear import of exogenous genes, novel plasmid DNA/importin-β conjugates, which consist of a biotinylated plasmid DNA and a recombinant streptavidin-fused importin-β, were prepared. The microinjection of plasmid DNA/importin-β conjugates into the cytoplasm of NIH3T3 cells resulted in the nuclear … More localization of conjugates and the higher expression efficiency, compared to intact plasmid DNA alone. These results indicate that plasmid DNA/importin-β conjugates would be an important tool to enhance the nuclear localization of exogenous DNA in non-viral gene delivery system. Moreover, the enhancement of internalization efficiency by dual ligands is an important factor for improving transfection efficiency. In addition, the effect of dual ligands depends on cell species; receptor-mediated and efficient internalization may be related to this enhanced transfection efficiency. Biodegradable polymeric vectors were obtained from chitosan and polylysines.
Obtained results on development of artificial multi-component vectors aimed at providing solutions to membrane crossing, endosomal escape and navigation through the nuclear pore. The combination of these nature-inspired and chemically originated approaches is bringing us continually closer to the concept of constructing an artificial virus capable of delivering viable nucleic acid-based pharmaceuticals to defined cells as molecular machines that can work even in vivo. Less

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (40 results)

All 2007 2006 2005 Other

All Journal Article (30 results) Book (4 results) Patent(Industrial Property Rights) (6 results)

  • [Journal Article] β-1,3-Glucan Schizophyllan Can Act as a One-dimensional Host to Arrange Icosahedral Carboranes2007

    • Author(s)
      M.Numata
    • Journal Title

      Chem. Lett. 36・5

      Pages: 668-669

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] β-1,3-Glucan Schizophyllan Can Act as a One-dimensional Host to Arrange Icosahedral Carboranes.2007

    • Author(s)
      M.Numata et al.
    • Journal Title

      Chem. Lett. 36(5)

      Pages: 668-669

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Sequential Chemical Modifications at the C-6 Positions of N-Phthaloyl-chitosan and Evaluation as a Gene Carrier2006

    • Author(s)
      T.Satoh
    • Journal Title

      Carbohydr. Res. 341・14

      Pages: 2406-2413

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Sequential Chemical Modifications at the C-6 Positions of N-Phthaloyl-chitosan and Evaluation as a Gene Carrier.2006

    • Author(s)
      T.Satoh et al.
    • Journal Title

      Carbohydr. Res. 341(14)

      Pages: 2406-2413

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Sequential Chemical Modifications at the C-6 Positions of N-Phthaloyl-chitosan and Evaluation as a Gene Carrier2006

    • Author(s)
      T.Satoh
    • Journal Title

      Carbohydr. Res. 341

      Pages: 2406-2413

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Enhanced nuclear import and transfection efficiency of plasmid DNA using streptavidin-fused importin-β2005

    • Author(s)
      T.Nagasaki
    • Journal Title

      J. Control. Release 103・1

      Pages: 199-207

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Reversible photoswitching in a cell-sized vesicle2005

    • Author(s)
      T.Hamada
    • Journal Title

      Langmuir 21・17

      Pages: 7626-7628

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary 2005 Annual Research Report
  • [Journal Article] Cholesterol-appended β-(1,3)-D-glucan schizophyllan for antisense oligonucleotides delivery to enhance the cellular uptake2005

    • Author(s)
      K.Koumoto
    • Journal Title

      Bull. Chem. Soc. Jpn. 78・10

      Pages: 1821-1830

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Linear double-stranded DNA that mimics an infective tail of virus genome to enhance transfection2005

    • Author(s)
      T.Anada
    • Journal Title

      J. Control. Release 108・2-3

      Pages: 529-539

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Enhanced nuclear import and transfection efficiency of plasmid DNA using streptavidin-fused importin-β.2005

    • Author(s)
      T.Nagasaki et al.
    • Journal Title

      J. Control. Release 103(1)

      Pages: 199-207

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Active DNA release from complexes"chapter for Non-viral gene therapy, edited by K. Taira, K. Kataoka, and T. Niidome, Springer-Verlag, Tokyo2005

    • Author(s)
      T.Nagasaki
    • Journal Title

      Chapter for Non-viral gene therapy

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Active transport of exogenous genes into the nucleus"chapter for Non-viral gene therapy, edited by K. Taira, K. Kataoka, and T. Niidome, Springer-Verlag, Tokyo.2005

    • Author(s)
      T.Kawazu
    • Journal Title

      Chapter for Non-viral gene therapy

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Reversible photoswitching in a cell-sized vesicle2005

    • Author(s)
      T.Hamada et al.
    • Journal Title

      Langmuir 21(17)

      Pages: 7626-7628

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Cholesterol-appended β-(1,3)-D-glucan schizophyllan for antisense oligonucleotides delivery to enhance the cellular uptake2005

    • Author(s)
      K.Koumoto et al.
    • Journal Title

      Bull Chem Soc. Jpn. 78(10)

      Pages: 1821-1830

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Linear double-stranded DNA that mimics an infective tail of virus genome to enhance transfection.2005

    • Author(s)
      T.Anada et al.
    • Journal Title

      J. Control. Release 108(2-3)

      Pages: 529-539

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Enhanced nuclear import and transfection efficiency of plasmid DNA using streptavidin-fused importin-β2005

    • Author(s)
      T.Nagasaki
    • Journal Title

      J.Control.Release 103・1

      Pages: 199-207

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Cholesterol-appended β-(1,3)-D-glucan schizophyllan for antisense oligonucleotides delivery to enhance the cellular uptake2005

    • Author(s)
      K.Koumoto
    • Journal Title

      Bull.Chem.Soc.Jpn. 78・10

      Pages: 1821-1830

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Linear duble-stranded DNA that mimics an infective tail of virus genome to enhance transfection2005

    • Author(s)
      T.Anada
    • Journal Title

      J.Control.Release 108・2-3

      Pages: 529-539

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Delivery of Antisense Oligonucleotides to Nuclear Telomere RNA by use of a Complex between Polysaccharide and Polynucleotide

    • Author(s)
      J.Minari
    • Journal Title

      Bull. Chem. Soc. Jpn. (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] The Concept of Molecular Machinery Is Useful for Design of Stimuli-Responsive Gene Delivery Systems in the Mammalian Cell

    • Author(s)
      T.Nagasaki
    • Journal Title

      J. Incl. Phenom. Macrocycl. Chem. (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] In vitro gene delivery HepG2 cells using a galactosylated 6-amino-6-deoxychitosan as a DNA carrier

    • Author(s)
      T.Satoh
    • Journal Title

      Carbohydr. Res. (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Dual-ligand effect of transferrin and transforming growth factor alpha on polyethyleneimine-mediated gene delivery

    • Author(s)
      S.Kakimoto
    • Journal Title

      J. Control. Release (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Delivery of Antisense Oligonucleotides to Nuclear Telomere RNA by use of a Complex between Polysaccharide and Polynucleotide.

    • Author(s)
      J.Minari et al.
    • Journal Title

      Bull Chem Soc. Jpn. (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] The Concept of Molecular Machinery Is Useful for Design of Stimuli-Responsive Gene Delivery Systems in the Mammalian Cell.

    • Author(s)
      T.Nagasaki et al.
    • Journal Title

      J. Incl. Phenom. Macrocycl. Chem. (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] In vitro gene delivery HepG2 cells using a galactosylated 6-amino-6-deoxychitosan as a DNA carrier.

    • Author(s)
      T.Satoh et al.
    • Journal Title

      Carbohydr. Res. (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Dual-ligand effect of transferrin and transforming growth factor alpha on polyethyleneimine-mediated gene delivery.

    • Author(s)
      S.Kakimoto et al.
    • Journal Title

      J. Control. Release (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Delivery of Antisense Oligonucleotides to Nuclear Telomere RNA by use of a Complex between Polysaccharide and Polynucleotide

    • Author(s)
      J.Minari
    • Journal Title

      Bull Chem. Soc. Jpn. (in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] The Concept of Molecular Machinery Is Useful for Design of Stimuli-Responsive Gene Delivery Systems in the Mammalian Cell

    • Author(s)
      T.Nagasaki
    • Journal Title

      J. Incl. Phenom, Macrocycl. Chem. (in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] β-1,3-Glucan Schizophyllan Can Act as a One-dimensional Host to Arrange Icosahedral Carboranes

    • Author(s)
      M.Numata
    • Journal Title

      Chem. Lett. (in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] In vitro gene delivery HepG2 cells using a galactosylated 6-amino-6-deoxychitosan as a DNA carrier

    • Author(s)
      T.Satoh
    • Journal Title

      Carbohydr. Res. (in press)

    • Related Report
      2006 Annual Research Report
  • [Book] "Active DNA release from complexes"chapter for Non-viral gene therapy (edited by K. Taira, K. Kataoka, and T. Niidome)2005

    • Author(s)
      T.Nagasaki
    • Publisher
      Springer-Verlag, Tokyo
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Book] "Active transport of exogenous genes into the nucleus"chapter for Non-viral gene therapy (edited by K. Taira, K. Kataoka, and T. Niidome)2005

    • Author(s)
      T.Kawazu
    • Publisher
      Springer-Verlag, Tokyo
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Book] "Active DNA release from complexes" chapter for Non-viral gene therapy, edited by K.Taira, K.Kataoka, and T.Niidome2005

    • Author(s)
      T.Nagasaki
    • Publisher
      Springer-Verlag, Tokyo
    • Related Report
      2005 Annual Research Report
  • [Book] "Active transport of exogenous genes into the nucleus" chapter for Non-viral gene therapy, edited by K.Taira, K.Kataoka, and T.Niidome2005

    • Author(s)
      T.Kawazu
    • Publisher
      Springer-Verlag, Tokyo
    • Related Report
      2005 Annual Research Report
  • [Patent(Industrial Property Rights)] β-1, 3-グルカン/カルボラン複合体2007

    • Inventor(s)
      新海征治, 為末真吾, 広瀬良治, 櫻井和朗, 長崎健, 沼田宗典
    • Industrial Property Rights Holder
      JST
    • Industrial Property Number
      2007-059771
    • Filing Date
      2007-03-09
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 輸造小胞脱出性核酸構造体2007

    • Inventor(s)
      新海征治, 長崎健, 柿本真司
    • Industrial Property Rights Holder
      JST
    • Industrial Property Number
      2007-131387
    • Filing Date
      2007-05-17
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Patent(Industrial Property Rights)] β-1,3-グルカン/カルボラン複合体2007

    • Inventor(s)
      新海征治, 為末真吾, 広瀬良治, 櫻井和朗, 長崎 健, 沼田宗典
    • Industrial Property Rights Holder
      JST
    • Industrial Property Number
      2007-059771
    • Filing Date
      2007-03-09
    • Related Report
      2006 Annual Research Report
  • [Patent(Industrial Property Rights)] ゲル形成用組成物2006

    • Inventor(s)
      横山昌幸, 村上義彦, 西田博, 長崎健
    • Industrial Property Rights Holder
      神奈川科学技術アカデミー・JST
    • Industrial Property Number
      2006-279565
    • Filing Date
      2006-10-13
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 6-アミノー6-デオキシキトサン誘導体から成る核酸導入剤2005

    • Inventor(s)
      新海征治, 長崎健, 佐藤琢, 狩野弘志
    • Industrial Property Rights Holder
      JST
    • Industrial Property Number
      2005-194612
    • Filing Date
      2005-07-04
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 6-アミノ-6-デオキシキトサン誘導体から成る核酸導入剤2005

    • Inventor(s)
      新海 征治, 長崎 健, 佐藤 琢, 狩野 弘志
    • Industrial Property Rights Holder
      JST
    • Industrial Property Number
      2005-194612
    • Filing Date
      2005-07-04
    • Related Report
      2005 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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