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Gene transfection by cationic liposome with a cationic cholesterol derivative

Research Project

Project/Area Number 12557207
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Physical pharmacy
Research InstitutionNagoya City University

Principal Investigator

NAKANISHI Mamoru  Nagoya City University, Graduate School of Pharmaceutical Sciences, Professor, 大学院・薬学研究科, 教授 (90090472)

Co-Investigator(Kenkyū-buntansha) HANDA Tetsuro  Kyoto University, Graduate School of Pharmaceutical Sciences, Professor, 大学院・薬学研究科, 教授 (00025719)
HIRASHIMA Naohide  Nagoya City University, Graduate School of Pharmaceutical Sciences, Assistant Professor, 大学院・薬学研究科, 助教授 (10192296)
OHWADA Tomohiko  The University of Tokyo, Graduate School of Pharmaceutical Sciences, Professor, 大学院・薬学系研究科, 教授 (20177025)
TOKUYAMA Satoru  NOF Corporation, Researcher, 研究員
OKU Naoto  University of Shizuoka, Professor, 薬学部, 教授 (10167322)
Project Period (FY) 2000 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥8,900,000 (Direct Cost: ¥8,900,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2001: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2000: ¥4,100,000 (Direct Cost: ¥4,100,000)
KeywordsGene transfection / Cationic cholesterol / Cationic liposome / Non-viral vector / Microscopy / Endocytosis / Biosurfactant / Gene therapy / 非ウイルスベクター / 膜融合
Research Abstract

We will demonstrate interesting cationic liposomes with novel cationic cholesterol derivatives, a new strategy in gene transfection developed by our group and the presently accepted molecular mechanism of gene transfection. Use of confocal laser scanning microscopy and atomic force microscopy in elucidating the molecular mechanism of gene transfection by cationic liposomes is also showed using examples from our own work. As delineated, both the confocal laser scanning microscopic and the atomic force microscopic results advocate for the involvement of the sequential three steps in gene transfection mediated by the cationic liposomes: endocytotic internalization of the lipoplexes into the target cells, endosome-lysosome fusion whereby the DNA gets released from the liposomes and moves towards the nucleus of the target cells and microtubule organization apparently involved in trafficking the transfected foreign genes to lysosomes. Furthermore, our experiment also shows couple of important strategies in gene transfection namely, use of liposomes made from biosurfactans and harnessing efficient gene transfection by activating the membrane-bound receptor molecules.

Report

(4 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (33 results)

All Other

All Publications (33 results)

  • [Publications] Hasagawa, S., Hirashima, N., Nakanishi, M.: "Comparative Study of Transfection Efficiency of Cationic Cholesterols Mediated by Liposomes-Based Gene Delivery"Bioorg. Med. Chem. Lett.. 12. 1299-1302 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kato, N., Nakanishi, M., Hirashima, N.: "Transbilayer Asymmetry of Phospholipids in the Plasma Membrane Regulates Exocytotic Release in Mast Cells"Biochem.. 41. 8068-8074 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Noguchi, A., Hirashima, N., Furuno, T., Nakanishi, M.: "Activation of Receptor Tyrosine Kinases Promotes Gene Transfection in Rat Neuronal PC12 Cells by Cationic Liposomes"Neurosci. Lett.. 325. 29-32 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Noguchi, A., Hirashima, N,.Nakanishi, M.: "Cationic Choresterol Promotes Gene Transfection Using the Nuclear Localization Signal in Protamine"Phamaceut. Res.. 19. 933-938 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mori, N., Suzuki, R., Furuno, T., McKay, DM.Wada, M., Teshima, R., Bienenstock, J., Nakanishi, M.: "Nerve-mast cell (RBL) interaction : RBL membrane ruffling occurs at the contact site with an activated neurite"Am J Physiol Cell Physiol.. 283. C1738-C1744 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Noguchi, S., Hirashima, N., Furuno, T., Nakanishi, M.: "Remarkable induction of apoptsis in cancer cells by a novel cationic liposome complexed with bcl-2 antisense oligonucleotide"J Control Release. 7. 313-320 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 中西 守他: "免疫学辞典"東京化学同人. 450 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hasegawa,S., Hirashima,N., Nakanishi,M.: "Comparative Study of Transfection Efficiency of Cationic Cholesterols Mediated by Liposomes-Based Gene Delevery"Bioorg. Med. Chem. Lett.. 12. 1299-1302 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kato,N., Nakanishi,M., Hirashima,N.: "Transbilayer Asymmetry of Phospholipids in the Plasma Membrane Regulates Exocytotic Release in Mast Cells"Biochem.. 41. 8068-8074 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Noguchi,A., Hirashima,N., Furuno,T., Nakanishi,M.: "Activation of Receptor Tyrosine Kinases Promotes Gene Transfection in Rat Neuronal PC12 Cells by Cationic Liposomes"Neurosci. Lett.. 325. 29-32 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Noguchi,A., Hirashima,N., Nakanishi,M.: "Cationic Cholesterol Promotes Gene Transfection Using the Nuclear Localization Signal in Protamine"Pharmaceut. Res.. 19. 933-938 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mori,N., Suzuki,R., Furuno,T., McKay,DM., Wada,M., Teshima,R., Bienenstock,J., Nakanishi,M.: "Nerve-mast cell (RBL) interaction: RBL membrane ruffling occurs at the contact site with an activated neurite"Am J Physiol Cell Physiol. 283. C1738-1744 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Noguchi,S., Hirashima,N., Furuno,T., Nakanishi,M.: "Remarkable induction of apoptosis in cancer cells by a novel cationic liposome conplexed with a bcl-2 antisense oligonucleotide"J Control Release. 7. 313-320 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hasegawa, S., Hirashima, N., Nakanishi, M.: "Comparative Study of Transfection Efficiency of Cationic Cholesterols Mediated by Liposomes-Based Gene Delivery"Bioorg. Med. Chem. Lett.. 12. 1299-1302 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kato, N., Nakanishi, M., Hirashima, N.: "Transbilayer Asymmetry of Phospholipids in the Plasma Membrane Regulates Exocytotic Release in Mast Cells"Biochem.. 41. 8068-8074 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Noguchi, A., Hirashima, N., Furuno, T., Nakanishi, M.: "Activation of Receptor Tyrosine Kinases Promotes Gene Transfection in Rat Neuronal PC12 Cells by Cationic Liposomes"Neurosci. Lett.. 325. 29-32 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Noguchi, A, Hirashima, N., Nakanishi, M.: "Cationic Choresterol Promotes Gene Transfection Using the Nuclear Localization Signal in Protamine"Pharmaceut. Res.. 19. 933-938 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Mori, N., Suzuki, R., Furuno, T., McKay, DM., Wada, M., Teshima, R., Bienenstock, J., Nakanishi, M.: "Nerve-mast cell (RBL) interaction : RBL membrane ruffling occurs at the contact site with an activated neurite"Am J Physiol Cell Physiol.. 283. C1738-C1744 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Noguchi, S., Hirashima, N., Furuno, T., Nakanishi, M.: "Remarkable induction of apoptsis in cancer cells by a novel cationic liposome complexed with a bcl-2 antisense oligonucleotide"J Control Release. 7. 313-320 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 中西 守他: "免疫学辞典"東京化学同人. 450 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Furuno, T., Hirashima, N., Onizawa, S., Sagiya, N., Nakanishi, M.: "Nuclear shuttling of mitogen-activated protein (MAP) kinase (extracellular signal-regulated kinase (ERK) 2) was dyuamically controlled by MAP/ERK kinase after antigen stimulation in RBL-2H3 cells"J. Immunol.. 166. 4416-4421 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nakanishi, M., Noguchi, A.: "Confocal and probe microscopy to study gene transfectionmediated by cationic Liposomes with a cationic cholesterol derivative"Adv. Drug Delivery Rev.. 52. 197-207 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hasegawa, S., Hirashima, N., Nakanishi, M.: "Microtubule involvements in the intracellular dynamics for gene transfection mediated by cationic liposomes"Gene Therapy. 8. 1669-1673 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Inoh, Y., Kitamoto, D., Hirashima, N., Nakanishi, M.: "Biosurfactants of MEL-A increase gene transfection mediated by cationic liposomes"Biochem. Biophys. Res. Commun.. 289. 57-61 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Noguchi, A., Hirashima, N., Furuno, T., Nakanishi, M.: "Activation of receptor tyrosine kineses promotes gene transfection in the neuronal PC12 cells by cationic liposomes"Neurosci. Lett.. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Noguchi, A., Hirashima, N., Nakanishi, M.: "A cationic cholesterol promote recognition of protamine having NLS in gene transfection"Pharmaceut. Res.. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] 中西 守 他: "免疫学辞典"東京化学同人. 450 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Dace,A.,Zhao,L.,Park,K.S.,Furuno,T.,Takamura,N.,Nakanishi,M.,West,B., et al.: "Hormone binding induces rapid proteasome-mediated degradation of thyroid hormone receptors."Proc.Natl.Acad.Sci.USA.. 97. 8985-8990 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ohshiro,H.,Suzuki,R.,Furuno,T.,Nakanishi,M.: "Atomic force microscopy to study direct neurite-mest cell (RBL) communication in vitro."Immunol.Lett.. 74. 211-214 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Suzuki,R.,Furuno,T.,Teshima,R.,Nakanishi,M.: "Bi-directional flow of in vitro mast cell-nerve communication observed by confocal laser scanning microscopy."Biol.Pharm.Bull.. 24. 291-294 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Furuno,T.,Hirashima,N.,Onizawa,S.,Sagiya,N.,Nakanishi,M.: "Nuclear shuttling of mitogen-activated protein (MAP) kinase (extracellular signal-regulated kinase (ERK) 2) was dynamically controlled by MAP/ERK kinase after antigen stimulation in RBL-2H3 cells."J.Immunol.. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Amano,T.,Furuno,T.,Hirashima,N.,Ohyama,N.,Nakanishi,M.: "Dynamics of intracellular granules with CD63-GFP in rat basophilic leukemia cells."J.Biochem.. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Fujiwara,T.,Hasegawa,S.,Hirashima,N,Nakanishi,M,Owada,T.: "Gene transfection activities of novel amphiphilic cholestane-polyamine conjugates"Biochim.Biophys.Acta. 1468. 396-402 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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