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Gene therapy for cardiovascular diseases : Development of newvector and evaluation of clinical strategy

Research Project

Project/Area Number 09357006
Research Category

Grant-in-Aid for Scientific Research (A).

Allocation TypeSingle-year Grants
Section展開研究
Research Field Circulatory organs internal medicine
Research InstitutionOSAKA University

Principal Investigator

TOSHIO Ogihara  Osaka University Graduate School of Medicine, Department of Geriatric Medicine, Professor, 医学系研究科, 教授 (60107042)

Co-Investigator(Kenkyū-buntansha) KANEDA Yasuhumi  Osaka University Graduate School of Medicine, Department of Geriatric Medicine, Professor, 医学系研究科, 教授 (10177537)
MORISHITA Ryuichi  Osaka Universitv Graduate School of Medicine, Department of Geriatric Medicine, Associate, 医学系研究科, 助教授 (40291439)
HIGAKI Jitsuo  Osaka University Graduate School of Medicine, Department of Geriatric Medicine, Associate, 医学系研究科, 助教授 (70189744)
HASEGAWA Mamoru  Osaka University Graduate School of Medicine, Department of Geriatric Medicine, 取締役研究所長
Project Period (FY) 1997 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥28,700,000 (Direct Cost: ¥28,700,000)
Fiscal Year 2000: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 1999: ¥5,200,000 (Direct Cost: ¥5,200,000)
Fiscal Year 1998: ¥5,500,000 (Direct Cost: ¥5,500,000)
Fiscal Year 1997: ¥13,000,000 (Direct Cost: ¥13,000,000)
KeywordsGene therapy / HVJ-liposome method / vector / restenosis / atherosclerosis / NFkB / decoy oligonucleotides / 血管新生 / HGF / 閉塞性動脈硬化症 / 心筋梗塞 / E2F / アンチセンス
Research Abstract

To develop gene therapy for cardiovascular diseases, we focused on HVJ-liposome method as an efficient and safe gene delivery system. We reported that HVJ-liposome method has low cytotoxicity and is a suitable system for transfection of gene or oligonucleotides into vessels and hearts.
We developed new strategies as treatments of cardiovascular diseases using this system. We showed the possibility of the therapy with gene modified grafted myocytes, and also reported that transfection of NFkB decoy oligonucleotides into hearts via coronary artery resulted in beneficial response to ischemic heart disease. Moreover, we reported the possibility of gene therapy for angiopathy after heart transplantation.
For vessel diseases, we showed the effect of transfection of P21 gene, AP-1 decoy, prostacyclin gene, or NFkB decoy on restenosis after angioplasty, using HVJ-liposome method. Also we reported the usefulness of rybozyme against apolipoprotein (a) for atherosclerosis.
Based on these results, we have already performed a clinical trial for restenosis after angioplasty using E2F decoy oligonucleotides, and now we are planning a new treatment for restenosis using NFkB decoy. To enhance the effects of these strategies, we are studying about the application of HVJ-liposome system now.

Report

(5 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (40 results)

All Other

All Publications (40 results)

  • [Publications] Higaki J,Ogihara T,: "Survival of grafts of genetically modified cardiac myocytes transfected with FITC-labeled oligodeoxynucleotides and β-galactosidase gene in non-infarcted srea, but not myocardial infarcted area."Gene Therapy. 4. 120-127 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Morishita R,Ogihara T,: "In Vivo Transfection of cis element "decoy" against NFkB binding site prevented myocardial infarction as gene therapy."Nature Medicine. 3. 894-899 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kaneda Y,Ogihara T,: "Inhibition of growth of human vascular smooth muscle cells by over-expression of p21 gene through Inductio of apoptosis."Hypertension. 31. 493-498 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Morishita R,Ogihara T,: "Dzau VJ.Role of AP-1 complex in angiotensin II-mediated transforming growth factor-β expression and growth of smooth muscle cells : using decoy approach against AP-1 binding site."Biochemical Biophysics Research Communication. 43. 361-367 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Morishita R,Ogihara T,: "Novel therapeutic strategy for atherosclerosis : ribozyme oligonucleotides against apolipoprotein (a) selectively inhibit apolipoprotein (a), but not plasminogen, gene expression."Circulation. 98. 1898-1904 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nishii T,Ogihara T,: "Angiotensinogen gene activating elements regulate blood pressure in the brain."Circulation Research. 85. 257-263 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Aoki M, Morishita R, Higaki J, Moriguchi A, Hayashi S, Matsushita H, Kida I, Tomita N, Sawa Y, Kaneda Y, Ogihara T.: "Survival of grafts of genetically modified cardiac myocytes transfected with FITC-labeled oligodeoxynucleotides and β-galactosidase gene in non-infarcted srea, but not myocardial infarcted area."Gene Therapy. 4. 120-127 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Morishita R, Sugimoto T, Aoki M, Kida I, Tomita N, Moriguchi A, Maeda K, Sawa Y, Kaneda Y, Higaki J, Ogihara T.: "In Vivo Transfection of cis element "decoy" against NFkB binding site prevented myocardial infarction as gene therapy."Nature Medicine. 3. 894-899 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Matsushita H, Morishita R, Kida I, Aoki M, Hayashi S, Tomita N, Yamamoto K, Moriguchi A, Noda A, Kaneda Y, Higaki J, Ogihara T.: "Inhibition of growth of human vascular smooth muscle cells by over-expression of p21 gene through induction of apoptosis."Hypertension. 31. 493-498 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Morishita R, Gibbons GH, Horiuchi M, Kaneda Y, Ogihara T, Dzau VJ.: "Role of AP-1 complex in angiotensin II-mediated transforming growth factor-β expression and growth of smooth muscle cells : using decoy approach against AP-1 binding site."Biochemical Biophysics Research Communication. 243. 361-367 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Morishita R, Yamada S, Yamamoto K, Tomita N, Kida I, Sakurabayashi I, Kikuchi A, Kaneda Y, Lawn R, Higaki J, Ogihara T.: "Novel therapeutic strategy for atherosclerosis : ribozyme oligonucleotides against apolipoprotein (a) selectively inhibit apolipoprotein (a), but not plasminogen, gene expression."Circulation. 98. 1898-1904 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nishii T, Moriguchi A, Morishita R, Yamada K, Nakamura S, Tomita N, Kaneda Y, Fukamizu A, Mikami H, Higaki J, Ogihara T.: "Angiotensinogen gene activating elements regulate blood pressure in the brain."Circulation Research. 85. 257-263 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Higaki J,Ogihara T,: "Survival of grafts of genetically modified cardiac myocytes transfected with FITC-labeled oligodeoxynucleotides and β-galactosidase gene in non-infarcted srea. but not myocardial infarcted ar"Gene Therapy. 4. 120-127 (1997)

    • Related Report
      2000 Annual Research Report
  • [Publications] Morishita R,Ogihara T,: "In Vivo Transfection of cis element "decoy" against NFkB binding site prevented myocardial infarction as gene therapy."Nature Medicine. 3. 894-899 (1997)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kaneda Y,Ogihara T,: "Inhibition of growth of human vascular smooth muscle cells by over-expression of p21 gene through Inductio of apoptosis."Hypertension. 31. 493-498 (1998)

    • Related Report
      2000 Annual Research Report
  • [Publications] Morishita R,Ogihara T,: "Dzau VJ.Role of AP-1 complex in angiotensin II-mediated transforming growth factor-β expression and growth of smooth muscle cells : using decoy approach against AP-1 binding site."Biochemical Biophysics Research Communication. 43. 361-367 (1998)

    • Related Report
      2000 Annual Research Report
  • [Publications] Morishita R,Ogihara T,: "Novel therapeutic strategy for atherosclerosis : ribozyme oligonucleotides against apolipoprotein (a) selectively inhibit apolipoprotein (a), but not plasminogen, gene expression."Circulation. 98. 1898-1904 (1998)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nishii T,Ogihara T,: "Angiotensinogen gene activating elements regulate blood pressure in the brain."Circulation Research. 85. 257-263 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Morishita R, Nakarnura S,: "Therapeutic angiogenesis induced by human recombinant hepatocyte growth factor in rabbit hind limb ischemia model as "cytokine supplement therapy""Hypertention. 33. 1379-1384 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Morishita R, Nishii T,: "Angiotensinogen gene activating elements regulate blood pressure in the brain"Circulation Research. 85. 257-263 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Morishita R, Aoki M,: "Inhibition of the p53 tumor suppressor gene resulted in growth of human aortic vascular smooth muscle cells (VSMC) : potential role of p53 in regulation of VSMC growth"Hypertension. 34. 192-200 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Morishita R, Nakamura S: "Activation of the brain angiotensin system by in vivo human angiotensin converting enzyme gene transfer in rats"Hypertension. 34. 302-308 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Morishita R, Hayashi S,: "Potential role of hepatocyte growth factor, a novel angiogenic growth factor, in peripheral arterial disease : down-regulation of HGF in response to hypoxia in vascular cells"Circulasion. 100. II301-II308 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Morishita R, Higaki J,: "In vivo evidence of importance of cardiac angiotensin converting enzyme in the pathogenesis of cardiac hypertrophy"Arteriosclerosis, Thrombosis&Vascular Biology. 20. 428-434 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yamada K,Moriguchi A,: "Efficient oligonucleotides delivery using HVJ-liposome method in the central nervous system" Hypertension. 28. 409-413 (1996)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hayashi S,Morishita R,: "In vivo transfer of gene and oligodeoxynucleotides into skin of fetal rats by incubation in amniotic fluid" Gene Therapy. 3. 878-885 (1996)

    • Related Report
      1998 Annual Research Report
  • [Publications] Morishita R,Gibbons GH,: "Molecular delivery system for antisense olgonucleotides;enhanced effectiveness of antisenseoligonucleotides by HVJ-liposome mediated transfer" Journal of Cardiovascular Pharmacology & Therapeutics. 2. 213-222 (1996)

    • Related Report
      1998 Annual Research Report
  • [Publications] Aoki M,Morishita R,: "Survival of genetically modified cardiac myocytes transfected with FITC-labeled oligodeoxynucleotides and β-galactosidase gene in non-infarcted area,but not myocardial infarcted area" Gene Therapy. 4. 120-127 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Aoki M,Morishita R,: "Efficient in vivo gene transfer into heart in rat myocardial infarction model using HVJ(Hemagglutinating Virus of Japan)liposome method" J Mol Cell Cardiol. 29. 949-959 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Morishita R,Sugimoto T,: "In vivo transfection of cis element “decoy"against NFkB binding site prevented myocardial infarction as gene therapy" Nature Medicine. 3. 894-899 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Morishita R,Aoki M,: "Kluwer Academic publisyers" Gene therapy for myocardial infarction, 531-550 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Morishita R,Aoki M,: "Kluwer Academic Publishers(in press)" Function analysis of tissue renin-angiotensin System using “Gain and Loss of Function“Approaches;In vivo test of in vitro hypothesis.in “Angiotensin II reseptor blockade;physiological, (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Aoki M: "Survival of grafts of genetically modified cardiac myocytes transfected with FITC-labeled oligodeoxynucleotides and B-galactosidase gene in non-infarcted area,but not myocardial infarcted area." Gene Therapy. 4. 120-127 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Aoki M: "In vivo transfer efficiency of antisense oligonucleotides into the myocardium using HVJ-liposome method." Biochemical Biophysics Research Communications. 231. 540-545 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Aoki M: "Efficient in vivo gene transfer into heart in rat myocardial infarction model using HVJ (Hemagglutinating Virus of Japan)-liposome method." J Mol Cell Cardiol. 29. 949-959 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Morishita R: "In Vivo Transfection of cis element "decoy" against NFkB binding site prevented myocardial infarction as gone therapy." Nature Medicine. 3. 894-899 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Suzuki J: "Prevention of graft coronary arteriosclerosis by anti sense cdk 2 kinase oligonucleatide." Natre Medicine. 3. 894-899 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Bai HZ: "In hibition of intimal hyperplasia after vein grafting by in vivo transfer of human senescent cell-derived inhibitor-1 gene." Gene Therapy. (in press).

    • Related Report
      1997 Annual Research Report
  • [Publications] Morishita R: "Ischemic Heart (in press)" Kluwer Academic Publishers,

    • Related Report
      1997 Annual Research Report
  • [Publications] Morishita R: "Angiotensin II receptor blockade : physiological and clinical implications" Kluwer Academic Publishers (in press),

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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