2000 Fiscal Year Final Research Report Summary
Gene therapy for cardiovascular diseases : Development of newvector and evaluation of clinical strategy
| Project/Area Number |
09357006
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| Research Category |
Grant-in-Aid for Scientific Research (A).
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | OSAKA University |
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Principal Investigator |
TOSHIO Ogihara Osaka University Graduate School of Medicine, Department of Geriatric Medicine, Professor, 医学系研究科, 教授 (60107042)
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| 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
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| Project Period (FY) |
1997 – 2000
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| Keywords | Gene therapy / HVJ-liposome method / vector / restenosis / atherosclerosis / NFkB / decoy oligonucleotides |
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| 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.
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[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)
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「研究成果報告書概要(欧文)」より
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[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)
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「研究成果報告書概要(欧文)」より
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[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)
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[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)
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「研究成果報告書概要(欧文)」より
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[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)
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「研究成果報告書概要(欧文)」より
