Production of human CD39 as an antithrombotic agent

生产人 CD39 作为抗血栓剂

• 批准号: 6741312
• 负责人: SOONSEOG JEONG
• 金额: $ 9.88万
• 依托单位: APT THERAPEUTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-01-16 至 2004-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6741312
• 关键词: CHO cells; acid anhydride hydrolase; adenosinetriphosphatase; anticoagulants; biotechnology; drug design /synthesis /production; enzyme activity; fibrinolytic agents; protein purification; transfection /expression vector

DESCRIPTION (provided by applicant): Production of a human apyrase protein as an antithrombotic agent is proposed. Thrombotic vascular occlusion due to abnormal platelet aggregation can lead to many diseases, including ischemic stroke, myocardial infarction, and restenosis after angioplasty or bypass surgery. Many of the current anti-platelet or fibrinolytic agents are undesirable due to the lack of specificity, narrow time window of administration, or severe adverse effects. Human ecto-apyrase has recently emerged as a critical endothelial thromboregulator with outstanding premise as an anti-platelet drug. The apyrase metabolizes extracellular ADP released by activated platelets, thereby inhibiting platelet aggregation and recruitment. We have cloned the human apyrase and expressed its extracellular domain in mammalian cells. Our recombinant apyrase exhibits an outstanding ADPase activity in vitro. We plan to integrate cutting edge technologies to create a robust CHO-cell based expression system suitable for large-scale production and efficient purification of biologically active recombinant proteins. We expect this research to provide an advanced system for producing the apyrase, and other proteins of therapeutic importance, at a substantially reduced cost, thus creating a reliable source of protein necessary for pre-clinical/clinical studies.

描述（由申请方提供）：拟生产人腺苷三磷酸双磷酸酶蛋白作为抗血栓形成剂。由于血小板聚集异常引起的血栓性血管闭塞可导致许多疾病，包括缺血性中风、心肌梗死以及血管成形术或旁路手术后的再狭窄。目前的许多抗血小板或纤维蛋白溶解剂由于缺乏特异性、给药时间窗窄或严重的不良反应而不受欢迎。人胞外腺苷三磷酸双磷酸酶是一种重要的内皮血栓调节剂，具有抗血小板药物的作用。腺苷三磷酸双磷酸酶代谢活化血小板释放的细胞外ADP，从而抑制血小板聚集和募集。我们克隆了人腺苷三磷酸双磷酸酶，并在哺乳动物细胞中表达了其胞外区。我们的重组腺苷三磷酸双磷酸酶在体外表现出突出的腺苷三磷酸酶活性。我们计划整合尖端技术，以创建一个强大的CHO细胞为基础的表达系统，适用于大规模生产和有效纯化的生物活性重组蛋白。我们希望这项研究能够提供一种先进的系统，用于以大幅降低的成本生产腺苷三磷酸双磷酸酶和其他具有治疗重要性的蛋白质，从而为临床前/临床研究提供可靠的蛋白质来源。