A novel Drug Delivery System Using HBV Envelop Protein Particles

使用 HBV 包膜蛋白颗粒的新型药物递送系统

基本信息

  • 批准号:
    13470243
  • 负责人:
  • 金额:
    $ 3.07万
  • 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:
    2001
  • 资助国家:
    日本
  • 起止时间:
    2001 至 2002
  • 项目状态:
    已结题

项目摘要

There are many hepatopathies that may be candidates for gene therapy. Gene therapy needs a vector that is carried together with its genes into a target cell or organ. Desirable vectors should be extremely safe, have good transfection efficiency, and demonstrate a high specificity for their target. In 1992, Kuroda et al. reported on the large amount of HBsAg envelope L particles that could be synthesized in yeast cells. HBV envelope L particles overproduced by yeast are hollow nanoparticles(average diameter 80nm) displaying the pre-S1 peptide indispensable for human liver-specific infection. Either a GFP(green fluorescence protein)-expression plasmid or a fluorescent dye(calcein) was incorporated into L particles by electroporation, and directly used for the transfection of various cells in vitro. Either GFP- or calcein-derived fluorescence was observed only in human liver-derived cells such as NuE and HepG2 not but WiDr and A431. We transplanted human hepatocellular carcinoma cells and human colon cancer cells subcutaneously in nude rats or nude mice. L particles with. GFP-expression plasmide or carcein were infected into the tumor-bearing nude rats or mice through tail vein. After 7 days, fluorescence was observed specifically in the subcutaneous heptocellular carcinoma, but not was observed in the subcutaneous colon cancer, brain, heart, lung, liver, spleen, kidney, adrenal gland, intestine, or muscle of rats or mice. When the human clotting factor IX gene, a therapeutic gene for hemophilia B, was transferred into the xenograft model by the L particles, therapeutic factor IX levels were obtained in the plasma for at least 1 month. In conclusion, HBsAg L particles showed a specific recognition ability for human-derived liver tissue and demonstrated a transgenie ability in an in vivo system.
有许多肝病可能是基因治疗的候选者。基因治疗需要一种载体,它与基因一起被携带到靶细胞或器官中。理想的载体应该是非常安全的,具有良好的转染效率,并表现出对它们的靶标的高特异性。1992年,黑田等人报道了可在酵母细胞中合成的大量HBsAg包膜L颗粒。由酵母菌过量产生的HBV包膜L颗粒是中空纳米颗粒(平均直径80nm),其展示人类肝脏特异性感染所必需的前S1肽。通过电穿孔将GFP(绿色荧光蛋白)表达质粒或荧光染料(钙黄绿素)掺入L颗粒中,并直接用于体外转染各种细胞。GFP或钙黄绿素衍生的荧光仅在人肝衍生的细胞如NuE和HepG2中观察到,但WiDr和A431没有。我们将人肝癌细胞和人结肠癌细胞分别移植到裸鼠和大鼠皮下。粒子与。将GFP表达质粒或癌黄素经尾静脉分别感染荷瘤裸鼠或裸鼠。7天后,在皮下肝细胞癌中特异性地观察到荧光,但在大鼠或小鼠的皮下结肠癌、脑、心脏、肺、肝、脾、肾、肾上腺、肠或肌肉中未观察到荧光。当通过L颗粒将人凝血因子IX基因(血友病B的治疗基因)转移到异种移植物模型中时,在血浆中获得治疗因子IX水平至少1个月。总之,HBsAg L颗粒显示出对人源性肝组织的特异性识别能力,并在体内系统中证明了转基因能力。

项目成果

期刊论文数量(38)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Maeda T., et al.: "Growth inhibition of mammalian cells by eosinophil cationic protein"Eur J Biochem. 269. 307-316 (2002)
Maeda T.等人:“嗜酸性粒细胞阳离子蛋白对哺乳动物细胞的生长抑制”Eur J Biochem。
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    0
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  • 通讯作者:
Shimizu S, et al.: "Detection of IL-2 receptor gene expression in peripheral blood of renal transplant patients"Surgery Today. (in press).
Shimizu S 等人:“肾移植患者外周血中 IL-2 受体基因表达的检测”《今日外科》。
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    0
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Yamamura T, et al.: "Immunosuppresire and anticancer effect of a mammalian ribonuclease targeting high-affinity interleukin-2 receptors"Eur J Surgery. (in press).
Yamamura T 等人:“针对高亲和力白细胞介素 2 受体的哺乳动物核糖核酸酶的免疫抑制和抗癌作用”Eur J 外科杂志。
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
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  • 通讯作者:
Yasui K., Arii S., Zhao C., Imoto I., Ueda M., Nagai H., Emi M., Inazawa J.: "TFDP1, CUL4A, and CDC16 identified as targets for amplification at 13q34 in hepatocellular carcinomas"Hepatology. 35. 1476-1484 (2002)
Yasui K.、Arii S.、Zhao C.、Imoto I.、Ueda M.、Nagai H.、Emi M.、Inazawa J.:“TFDP1、CUL4A 和 CDC16 被确定为肝细胞癌 13q34 扩增的靶标”
  • DOI:
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  • 期刊:
  • 影响因子:
    0
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Morise Z, et al.: "Reactive oygln species and vascular celladhesion moleaclar-1 in clistant organ frilure following hile duct obstruction in mice"Digestive Deseases and Sciences. (in press).
Morise Z 等人:“小鼠肝管阻塞后粘膜器官中的反应性 oygln 种类和血管细胞粘附 molecularaclar-1”《消化疾病与科学》。
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    0
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UEDA Masakazu其他文献

UEDA Masakazu的其他文献

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{{ truncateString('UEDA Masakazu', 18)}}的其他基金

Development of novel drugs for the surgical field by intelligent bionanocapsule
智能生物纳米胶囊开发外科领域新药
  • 批准号:
    18390352
  • 财政年份:
    2006
  • 资助金额:
    $ 3.07万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Tissue specific and safety pinpoint targeting by bionano-capusele
通过生物纳米胶囊进行组织特异性和安全精确定位
  • 批准号:
    15390383
  • 财政年份:
    2003
  • 资助金额:
    $ 3.07万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Molecular targeting against growth factor receptors by a novel drug compord of human fusion proteins
人类融合蛋白的新型药物组合物针对生长因子受体的分子靶向
  • 批准号:
    09470258
  • 财政年份:
    1997
  • 资助金额:
    $ 3.07万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Novel Anti-Cancer Drug Composed of Human Proteins
由人类蛋白质组成的新型抗癌药物
  • 批准号:
    07457262
  • 财政年份:
    1995
  • 资助金额:
    $ 3.07万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Molecular biological approach for a dignasis and me chanism of sepsis
脓毒症诊断和机制的分子生物学方法
  • 批准号:
    05454364
  • 财政年份:
    1993
  • 资助金额:
    $ 3.07万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (B)
Pathophysiology of water. electrolyte balance on surgical stress and application of therapy
水的病理生理学。
  • 批准号:
    63570611
  • 财政年份:
    1988
  • 资助金额:
    $ 3.07万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (C)

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Development of cancer missile therapy targeting amino acid transporter LAT1 by alpha emitting nuclide
通过α发射核素开发针对氨基酸转运蛋白LAT1的癌症导弹疗法
  • 批准号:
    18K07323
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使用外泌体开发针对口腔癌细胞的 siRNA/导弹疗法
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    17H04402
  • 财政年份:
    2017
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Creation of cell-internalizing antibody for novel tumor endothelial missile therapy
为新型肿瘤内皮导弹疗法创建细胞内化抗体
  • 批准号:
    20790134
  • 财政年份:
    2008
  • 资助金额:
    $ 3.07万
  • 项目类别:
    Grant-in-Aid for Young Scientists (B)
Development of the Gene-missile therapy against human malignant gliomas using monocyte as a carrier.
使用单核细胞作为载体开发针对人类恶性胶质瘤的基因导弹疗法。
  • 批准号:
    09671431
  • 财政年份:
    1997
  • 资助金额:
    $ 3.07万
  • 项目类别:
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Studies for clinical application of missile therapy for cancer.
癌症导弹治疗的临床应用研究。
  • 批准号:
    02454318
  • 财政年份:
    1990
  • 资助金额:
    $ 3.07万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (B)
Adjuvant therapy for lung cancer. - a missile therapy using monoclonal antibody
肺癌的辅助治疗。
  • 批准号:
    61480296
  • 财政年份:
    1986
  • 资助金额:
    $ 3.07万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (B)
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