Multiplexed screening of protein expression libraries

蛋白质表达文库的多重筛选

基本信息

批准号：
7920500
负责人：
LAWRENCE Michael KAUVAR
金额：
$ 48.05万
依托单位：
EXPERIMED BIOSCENCE, INC.
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-11 至 2010-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7920500
关键词：
Address Affinity Algorithms Antibodies Antibody Diversity Antibody-Producing Cells Antigens B-Lymphocytes Bacteriophages Binding Biological Biological Assay Bypass Cell fusion Cells Clinical Communicable Diseases Computational algorithm DNA Data Databases Detection Dimensions Disease Diversity Library Drug Delivery Systems Drug Industry Equipment and supply inventories Eukaryotic Cell Evolution Expression Library Family Family member Funding Generations Grant Human Hybridomas Image Analysis Immunoglobulin Light Chain Genes Individual Inflammatory Label Left Legal patent Libraries Life Location Malignant Neoplasms Maps Marketing Methods Microscopic Miniaturization Monoclonal Antibodies Mus Mutation Peptide Hydrolases Peptides Pharmaceutical Preparations Phase Philosophy Plasmids Predisposition Process Proliferating Property Protein Binding Protein Engineering Proteins Recombinant Antibody Recombinants Recovery Reporter Reporting Resolution Retrieval Route Screening procedure Serum Serum Proteins Source Specificity Splenocyte Spottings Synthetic Genes System T-Lymphocyte Technology Therapeutic Therapeutic antibodies Time Tissues Transfection Vaccination Work base combinatorial commercial application computerized data processing cost cytokine drug candidate drug development improved interest member novel novel strategies protein expression scaffold software systems submicron trend

项目摘要

DESCRIPTION (provided by applicant): In Phase I of this project, Trellis Bioscience, Inc. has validated a proprietary screening technology for multiplexed characterization of the secreted protein from individual live cells, enabling detection and propagation of rare favorable cells. The technology was applied to murine splenocytes and hybridomas, achieving a specificity (quality) threshold that is markedly higher than is feasible for other antibody screening technologies. The identified clones were too rare for recovery by conventional means lacking the extreme miniaturization of the Trellis approach (100,000 fold reduction). The present Phase II request for funding is to enable extension of the technology from murine hybridomas to two distinctive diversity sources: recombinant antibodies, and recombinant small peptides. Each addresses market needs not satisfied by murine hybridomas. Successful extension to recombinant antibodies will allow the recovery of human derived antibodies against infectious diseases, extending the benefits of vaccination to diseases for which a mass innoculation campaign is impractical or inappropriate. Peptides are of particular interest for targeting intracellular drug targets not amenable to antibody treatment. Extension to these uses requires a substantive increase in throughput of the screening system. Accordingly, Aim 1 is focused on increasing the multiplexing capacity of the assay and improving the efficiency and throughput of the image analysis system, while Aims 2 and 3 are focused on adapting the technology and demonstrating its capabilities in the two fields of interest. Trellis Bioscience is developing a technology that decreases the time and cost required to discover antibody therapeutics, which now represent the fastest growing segment of the pharmaceutical industry. Drugs in this class are being used to treat cancer and inflammatory diseases, as well as infectious disease. A further extension of the technology to peptide therapeutics will allow the efficient development of drugs to treat diseases that are not currently amenable to antibody based approaches.

描述（由申请人提供）：在该项目的第一阶段，Trellis Bioscience, Inc. 验证了一种专有的筛选技术，用于对单个活细胞分泌的蛋白质进行多重表征，从而能够检测和繁殖稀有的有利细胞。该技术应用于小鼠脾细胞和杂交瘤，实现了明显高于其他抗体筛选技术的特异性（质量）阈值。所鉴定的克隆太稀有，无法通过缺乏网格方法极端小型化（减少 100,000 倍）的传统方法来恢复。目前第二阶段的资金请求是将技术从鼠杂交瘤扩展到两个独特的多样性来源：重组抗体和重组小肽。每个都解决了鼠杂交瘤无法满足的市场需求。成功扩展到重组抗体将允许恢复针对传染病的人源抗体，将疫苗接种的益处扩展到大规模接种运动不切实际或不适当的疾病。肽对于靶向不适合抗体治疗的细胞内药物靶标特别感兴趣。扩展这些用途需要大幅增加筛选系统的吞吐量。因此，目标 1 的重点是增加检测的多重能力并提高图像分析系统的效率和吞吐量，而目标 2 和 3 的重点是调整该技术并展示其在两个感兴趣领域的能力。 Trellis Bioscience 正在开发一种技术，可以减少发现抗体疗法所需的时间和成本，抗体疗法目前代表了制药行业增长最快的部分。此类药物用于治疗癌症、炎症性疾病以及传染病。该技术进一步扩展到肽疗法将有助于有效开发药物来治疗目前不适用于基于抗体的方法的疾病。