Trial research for practical use of the reagent for gene expression control by Decoy oligo nucleotide.
Decoy寡核苷酸基因表达调控试剂的实用化试验研究。
基本信息
- 批准号:11557020
- 负责人:
- 金额:$ 7.68万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (B).
- 财政年份:1999
- 资助国家:日本
- 起止时间:1999 至 2000
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
We inspected availability, reproducibility and stability of novel gene therapy using the combination of "suppression of disease-related gene expression by a decoy for transcription factor" and "gene transfer by hemagglutinating virus of Japan (HVJ)- liposome".Using HVJ-liposome method, we transferred Sp1 decoy into cultured cancer cells (A549 and U251 cells). The TNF-alpha-mediated expression of both VEGF and TGF betal and tissue factor (TF) by the cancer cells could be simultaneously suppressed to less than 30% by transfection of Sp1 decoy but not by mutated-Sp1 decoy. In addition, in vitro invasiveness, synthesis of mRNA for urokinase-type plasminogen activator, andcell proliferation of both cell lines were also inhibited to 40% by the transfection of only Sp1 decoy. These results suggested that the Sp1 decoy strategy would be effective for regulating tumor growth by simultaneously reducing cancer cell (a) angiogenic growth factor expression, (b) proliferation, and (c) invasiveness. In rabbit balloon injury arteria carotis intima thickening model, NF-kB decoy suppressed the degree of vasoconstriction after injury to about 50%. By using HVJ- liposome, efficiency of NF-kB decoy transfer to vascular wall becomes higher than that of naked NF-kB decoy only. Otherwise, AP-1 was effective for hypoxia stimuli. These are suggested that gene therapy by decoy transfer by HVJ-liposome was extremely effective and has a great advantage for other current ones.However, stable activity of HVJ- liposome is dependent on quality of the lipids used for liposome preparation (oxidation degrees) and conditions of lipid film. Guarantee period for relatively high efficiency of gene transfer is about 10 days under N2 gas at -20℃ in dark. Therefore, we concluded that the improvements of lipids and conservation form of product are necessary, in order to commercial supply of HVJ-liposome.
本研究采用日本血凝病毒(HVJ)-脂质体法,将Sp1诱饵基因导入体外培养的肺癌细胞(A549和U251细胞)中,考察了“转录因子诱饵抑制疾病相关基因表达”和“HVJ-脂质体基因转移”相结合的新型基因治疗方法的有效性、重复性和稳定性。肿瘤坏死因子-α介导的VEGF和TGF β 1和组织因子(TF)的表达可以同时被抑制到低于30%的转染的Sp1诱饵,但不是由突变的Sp1诱饵。此外,两种细胞系的体外侵袭力、尿激酶型纤溶酶原激活物mRNA的合成和细胞增殖也被单独转染Sp1诱饵抑制至40%。这些结果表明,Sp1诱饵策略通过同时降低癌细胞(a)血管生成生长因子表达、(B)增殖和(c)侵袭性而有效调节肿瘤生长。在兔颈动脉球囊损伤后内膜增厚模型中,NF-kB诱骗剂抑制损伤后血管收缩程度约50%。通过使用HVJ-脂质体,NF-kB诱饵转移到血管壁的效率变得高于仅裸NF-kB诱饵的效率。另外,AP-1对缺氧刺激有效。这些结果表明HVJ脂质体诱饵转移基因治疗是非常有效的,具有很大的优势,但HVJ脂质体的稳定活性取决于脂质体制备所用脂质的质量(氧化程度)和脂质膜的条件。在-20℃、N_2气氛下、黑暗条件下,基因转移效率较高的保证期为10天左右。因此,我们得出结论,脂质体的改进和产品的保存形式是必要的,以使HVJ-脂质体的商业供应。
项目成果
期刊论文数量(44)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Nakagawa K et al: "Angiogenesis and Its Regulation: Roles of Vascular Endothelial Cell Growth Factor(VEGF)" Semin Thromb Hemost. in press.
Nakakawa K 等人:“血管生成及其调节:血管内皮细胞生长因子 (VEGF) 的作用”Semin Thromb Hemost。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Nakagawa K, et al: "Angiogenesis and its regulation : Roles of vascular endothelial cell growth factor (VEGF)."Thromb Hemost. 26(1). 61-66 (2000)
Nakakawa K 等人:“血管生成及其调节:血管内皮细胞生长因子 (VEGF) 的作用。”Thromb Hemost。
- DOI:
- 发表时间:
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- 影响因子:0
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- 通讯作者:
Kitamoto S, Egashira K, Kataoka C, Koyanagi M, Katoh M, Shimokawa H, Morishita R, Kaneda Y, Sueishi K, Takeshita A.: "Increased activity of nuclear factor-kappaB participates in cardiovascular remodeling induced by chronic inhibition of nitric oxide synth
Kitamoto S、Egashira K、Kataoka C、Koyanagi M、Katoh M、Shimokawa H、Morishita R、Kaneda Y、Sueishi K、Takeshita A.:“核因子-kappaB 活性增加参与一氧化氮慢性抑制诱导的心血管重塑
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Egashira K. et al.: "Anti-monocyte chemoattractant protein-1 gene therapy inhibits vascular remodeling in rats: blockade of MCP-1 activity after intramuscular transfer of a mutant gene inhibits vascular remodeling induced by chronic blockade of NO synthes
Egashira K.等人:“抗单核细胞趋化蛋白-1基因疗法抑制大鼠血管重塑:肌肉内转移突变基因后阻断MCP-1活性可抑制慢性阻断NO合成诱导的血管重塑
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Nakagawa K, Chen YX, Ishibashi H, Yonemitsu Y, Murata T, Hata Y, Nakashima Y, Sueishi K.: "Angiogenesis and its regulation : roles of vascular endothelial cell growth factor."Semin Thromb Hemost. 26(1). 61-66 (2000)
Nakakawa K、Chen YX、Ishibashi H、Yonemitsu Y、Murata T、Hata Y、Nakashima Y、Sueishi K.:“血管生成及其调节:血管内皮细胞生长因子的作用。”Semin Thromb Hemost。
- DOI:
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- 影响因子:0
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NAKAGAWA Kazunori其他文献
NAKAGAWA Kazunori的其他文献
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{{ truncateString('NAKAGAWA Kazunori', 18)}}的其他基金
Pathological studies on molecular basis of failure of vascular homeostasis and pathological vascular remodeling.
血管稳态失败和病理性血管重塑的分子基础的病理学研究。
- 批准号:
22590315 - 财政年份:2010
- 资助金额:
$ 7.68万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Moleculo-Pathological studies on intracellular cross-talk signal in angiogenic and lymphoangiogenic process
血管生成和淋巴管生成过程中细胞内串扰信号的分子病理学研究
- 批准号:
19590352 - 财政年份:2007
- 资助金额:
$ 7.68万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Moleculo-Pathological studies on intracellular cross-talk signal in angiogenic process.
血管生成过程中细胞内串扰信号的分子病理学研究。
- 批准号:
14370078 - 财政年份:2002
- 资助金额:
$ 7.68万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Patho-physiological studies on cellular interaction in vascular injury and vascular remodeling
血管损伤和血管重塑中细胞相互作用的病理生理学研究
- 批准号:
11470059 - 财政年份:1999
- 资助金额:
$ 7.68万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Molecular pathological studies on physiological function of VEGF in atherosclerotic Vessels
VEGF在动脉粥样硬化血管中生理功能的分子病理学研究
- 批准号:
09470064 - 财政年份:1997
- 资助金额:
$ 7.68万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Molecular pathological studies on physiological function of VEGF in atherosclerotic Vessels
VEGF在动脉粥样硬化血管中生理功能的分子病理学研究
- 批准号:
07670252 - 财政年份:1995
- 资助金额:
$ 7.68万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
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