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In vivo gene therapy utilising transferrin receptor-operated transfer

Research Project

Project/Area Number 12835004
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research InstitutionTokyo Medical and Dental University

Principal Investigator

SHICHIRI Masayoshi  Tokyo Medical and Dental University, Department of Clinical and Molecular Endocrinology, Lecturer, 医学部・附属病院, 講師 (10206097)

Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2001: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2000: ¥1,900,000 (Direct Cost: ¥1,900,000)
Keywordsgene therapy / LDL receptor deficiency / balloon-injured rat / transferrin receptor / max gene / Light Cycler / 遺伝子導入 / max / transferrin受容体
Research Abstract

Cationic liposome DNA complex (CLDC) intravenous gene delivery has been shown to direct gene expression to vascular endothelial cells, monocytes, and macrophages. CLDC gene delivery avoids immune system reactions associated with viral vectors, yet the low efficiency of gene delivery using CLDC has limited the use of non-viral vectors for gene therapy. Ligand-facilitated transfer of CLDC has been shown to markedly increase in vitro gene delivery efficiency, but has not increased in vivo efficiency to the magnitude of adenoviral vectors and has remained unsuccessful in applications to systemic gene therapy. Introduction of ligands such as transferrin and asialofetuin into a CLDC has been reported to generate in vivo expression of reporter plasmids while others report low transfer efficiency. We have demonstrated that a combination of CLDC-transferrin enhanced intravenous delivery in circulating leukocytes. Transferrin-facilitated intravenous delivery of cationic liposome CDNA complexes could serve as an important adjunct therapy for the treatment of disorders, especially those in which deficiency of a single gene can be replaced by transfer of an exogenous gene into circulating cells.

Report

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

    (31 results)

All Other

All Publications (31 results)

  • [Publications] Shichiri M, Yokokura M, Marumo F, Hirata Y: "Endothelin-1 inhibits apoptosis of vascular smooth muscle cells induced by nitric oxide and serum deprivation via MAP kinase pathway"Arteriosclerosis Throm Vasc Biol. 20. 989-997 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ohta K, Shichiri M, Kameya T, Matsubara O, Imai T, Marumo F, Hirata Y: "Thymic hyperplasia as a source of ectopic ACTH production"Endocrine Journal. 47. 487-492 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Doi M, Shichiri M, Yoshida Y, Marumo F, Hirata Y: "Suppression of integrin αV expression by endothelin-1 in vascular smooth muscle cells"Hypertension Research. 23. 643-649 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Doi M, Shichiri M, Katsuyama K, Marumo F, Hirata Y: "Cytokine-activated p42/p44 MAP kinase is involved in inducible nitric oxide synthase gene expression independent from NF-κB activation in vascular smooth muscle cells"Hypertension Research. 23. 659-667 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Iwasaki H, Shichiri M, Marumo F, Hirata Y: "Adrenomedullin stimulates proline-rich tyrosine kinase 2 in vascular smooth muscle cells"Endocrinology. 142. 564-572 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shiigai T, Shichiri M: "Late escape from the anti-proteinuric effect of ACE inhibitors in non-diabetic renal disease"American Journal of Kidney Diseases. 37. 477-483 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ishimaru S, Shichiri M, Mineshita S, Hirata Y: "Role of endothelin-1/endothelin receptor system in endotoxic shock rats"Hypertension Research. 24. 119-126 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shichiri M, Hirata Y: "Anti-angiogenesis signals by endostatin"FASEB Journal. 15. 1044-1053 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Iwasaki H, Sato R, Shichiri M, Hirata Y: "A patient with type 1 diabetes mellitus and cerebellar ataxia associated with high titer of circulating anti-glutamic acid decarboxylase antibodies"Endocrine Journal. 48. 261-268 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Matsushita M, Shichiri M, Imai T, Iwashina M, et al.: "Co-expression of urotensin II and its receptor (GPR14) in human cardiovascular and renal tissues"Journal of Hypertension. 19. 2185-2190 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Doi M, Shichiri M, Katsuyama K, Ishimaru S, Hirata Y: "Cytokane-activated Jak-2 is involved in inducible nitric oxide synthase expression independent from NF-κB activation in vascular smooth muscle cells"Atherosclerosis. 160. 123-132 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shichiri M, Yoshinaga K, Hisatomi H, Sugihara K, Hirata Y: "Genetic and epigenetic inactivation of mitotic checkpoint genes hBUB1 and hBUBR1 and their relationship to survival"Cancer Research. 62. 13-17 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shichiri M, Yokokura M, Marumo F, Hirata Y: "Endothelin-1 inhibits apoptosis of vascular smooth muscle cells induced by nitric oxide and serum deprivation via MAP kinase pathway"Arteriosclerosis Throm Vasc Biol. 20. 989-997 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ohta K, Shichiri M, Kameya T, Matsubara O, Imai T, Marumo F, Hirata Y: "Thymic hyperplasia as a source of ectopic ACTH production"Endocrine. 47. 487-492 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Doi M, Shichiri M, Yoshida Y, Marumo F, Hirata Y: "Suppression of integrin av expression by endothelin-1 in vascular smooth muscle cells"Hypertension Res. 23. 643-649 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Doi M, Shichiri M, Katsuyama K, Marumo F, Hirata Y: "Cytokine-activated p42/p44 MAP kinase is involved in inducible nitric oxide synthase gene expression independent from NF-kB activation in vascular smooth muscle cells"Hypertension Res. 23. 659-667 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Iwasaki H, Shichiri M, Marumo T, Hirata Y: "Adrenomedullin stimulates proline-rich tyrosine kinase 2 in vascular smooth muscle cells"Endocrinology. 142 : 564. 572 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shiigai T, Shichiri M: "Late escape from the anti-proteinuric effect of ACE inhibitors in non-diabetic renal disease"Am J Kidney Dis. 37. 477-483 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ishimaru S, Shichiri M, Mineshita S, Hirata Y: "Role of endothelin-1 /endothelin receptor system in endotoxic shock rats"Hypertension Res. 24. 119-126 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shichiri M, Hirata Y: "Anti-angtogenesis signals by endostatin"FASEB J. 15. 1044-1053 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Iwasaki H, Sato R, Shichiri M, Hirata Y: "A. patient with type 1 diabetes mellitus and cerebellar ataxia associated with high titer of circulating anti-glutamic acid decarboxylase antibodies"Endocrine J. 48. 261-268 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] M, Shichiri M, Imai T, Iwashina M, Tanaka H, Takasu N, Hirata Y: "Co-expression of urotensin II and its receptor (GPR14) in human cardiovascular and renal tissues"J Hypertens. 19. 2185-2190 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] . Doi M, Shichiri M, Katsuyama K, Ishimaru S, Hirata Y: "Cytokine activated Jak-2 is involved in inducible nitric oxide synthase expression independent from NF-kB activation in vascular smooth muscle cells"Atherosclerosis. 160. 123-132 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shichiri M, Yoshinaga K, Hisatomi H, Sugihara K, Hirata Y: "Genetic and epigenetic inactivation of mitotic checkpoint genes hBUB1 and hBUBR1 and their relationship to survival"Cancer Res. 62. 13-17 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shichiri M, Yokokura M, Marumo F, Hirata Y: "Endothelin-1 inhibits apoptosis of vascular smooth muscle cells induced by nitric oxide and serum deprivation via MAP kinase pathway"Arteriosclerosis Throm Vasc Biol. 20. 989-997 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Iwasaki H, Shichiri M, Marumo F, Hirata Y: "Adrenomedullin stimulates proline-rich tyrosine kinase 2 in vascular smooth muscle cells"Endocrinology. 142. 564-572 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Shichiri M, Hirata Y: "Anti-angiogenesis signals by endostatin"FASEB Journal. 15. 1044-1053 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Matsushita M, Shichiri M, Imai T, Iwashina M, et al.: "Co-expression of urotensin II and its receptor (GPR14) in human cardiovascular and renal tissues"Journal of Hypertension. 19. 2185-2190 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Doi M, Shichiri M, Katsuyama K, Ishimaru S, Hirata Y: "Cytokine-activated Jak-2 is involved in inducible nitric oxide synthase expression independent from NF-_KB activation in vascular smooth muscle cells"Atherosclerosis. 160. 123-133 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Shichiri M, Yoshinaga K, Hisatomi H, Sugihara K, Hirata Y: "Genetic and epigenetic inactivation of mitotic checkpoint genes hBUB1 and hBUBR1 and their relationship to survival"Cancer Research. 62. 13-17 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] SHICHIRIM,HIRATA Y: "Anti-angiogenesis signals by endostatin"FASEB Journal. (in press). (2001)

    • Related Report
      2000 Annual Research Report

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

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