A CELL LINE FOR ANTIASTHMA DRUG DISCOVERY

用于发现抗哮喘药物的细胞系

• 批准号: 6742891
• 负责人: WEIHUA YUAN
• 金额: $ 13.2万
• 依托单位: BIOTECHPLEX CORPORATION
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-03-11 至 2004-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6742891
• 关键词: SDS polyacrylamide gel electrophoresis; asthma; bioassay; biological signal transduction; biotechnology; cell line; drug discovery /isolation; genetic manipulation; high throughput technology; interleukin 13; interleukin 4; intermolecular interaction; northern blottings; plasmids; polymerase chain reaction; reporter genes; respiratory epithelium; tissue /cell preparation; transfection /expression vector; western blottings

DESCRIPTION (provided by applicant): BioTechPlex Corporation (BioTechPlex) proposes to develop a stable, genetically engineered human bronchial epithelial cell line that can produce a measurable signal when an "asthma specific" regulatory protein in a selected signal transduction pathway is activated. As activation of this selected regulatory protein appears to be specific or at least markedly enhanced in allergic airways, and this signal transduction pathway plays a central role in the inflammation and remodeling in airways in patients with asthma, an immortalized cell line with an enhanced "asthma-specific" signal transduction mechanism would provide a new assay suitable for high throughput screening for anti-asthmatic drugs. In Phase I, we will construct the necessary plasmids and vectors for the transfection of a stable epithelial cell line to enhance the presence of this regulatory protein. We will evaluate the success of this transfection using receptor-induced activation of a luminescent reportable moiety. In Phase II, BioTechPlex will further develop the capabilities of this cell line. This project will broadly impact drug discovery research in asthma, allergy and inflammation. It fulfills the needs and missions of the SBIR solicitations by several institutes of the NIH including: 1) the Asthma, Allergy and Inflammation program at the National Institutes of Allergy and Infectious Diseases (NIAID), 2) the understanding and treatment of COPD and asthma at NHLBI; and 3) the development of new assays based on molecular targets that interact with signal transduction at the National Cancer Institute, NCI.

描述(由申请人提供)：BioTechPlex公司(BioTechPlex)建议开发一种稳定的、经基因工程处理的人类支气管上皮细胞系，当选定信号转导途径中的“哮喘特异性”调节蛋白被激活时，该细胞系可以产生可测量的信号。由于这种被选择的调节蛋白的激活在过敏性呼吸道中似乎是特异的或至少是显著增强的，并且这一信号转导途径在哮喘患者的气道炎症和重塑中发挥着核心作用，因此具有增强的“哮喘特异性”信号转导机制的永生化细胞系将为高通量筛选抗哮喘药物提供一种新的检测方法。在第一阶段，我们将构建必要的质粒和载体，以转染稳定的上皮细胞系，以增强这种调节蛋白的存在。我们将使用受体诱导的发光可报告部分的激活来评估这种转基因的成功。在第二阶段，BioTechPlex将进一步开发该细胞系的能力。该项目将广泛影响哮喘、过敏和炎症方面的药物发现研究。它满足了NIH多个研究所的SBIR征集的需求和使命，包括：1)国家过敏和传染病研究所(NIAID)的哮喘、过敏和炎症计划；2)NHLBI对COPD和哮喘的理解和治疗；以及3)基于与NCI国家癌症研究所信号转导相互作用的分子靶标开发新的分析方法。