Phage Display Isolation of Antibodies against Antigenically Conserved Membrane Pr

抗抗原保守膜抗体的噬菌体展示分离

• 批准号: 8309899
• 负责人: Benjamin Jacob Doranz
• 金额: $ 21.42万
• 依托单位: INTEGRAL MOLECULAR
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2014-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8309899
• 关键词: Abbreviations; Adjuvant; Antibodies; Antigens; Avidity; Bacteriophages; Binding; Biomedical Research; Cells; Cellular Membrane; Detection; Detergents; Development; Diagnostic; Drug Delivery Systems; Environment; Epitopes; G-Protein-Coupled Receptors; Immobilization; Immunoglobulin G; Integral Membrane Protein; Ion Channel; Libraries; Licensing; Lipid Bilayers; Lipids; Marketing; Membrane; Membrane Proteins; Methods; Molecular Conformation; Monoclonal Antibodies; Pathway interactions; Phage Display; Preparation; Protocols documentation; Reagent; Research; Role; Signal Transduction; Source; Specificity; Structure; Technology; Testing; TimeLine; Virus-like particle; cell type; human PHEMX protein; human disease; immunogenicity; improved; new technology; receptor; receptor density; receptor function; therapeutic development

DESCRIPTION (provided by applicant): We propose to use a novel technology, the Lipoparticle, to capture and concentrate structurally intact membrane proteins in a format amenable to phage panning for MAb isolation. The use of Lipoparticles to pan phage display libraries represents a valuable approach for obtaining antibodies against conserved membrane protein antigens because 1) Lipoparticles contain high concentrations of conformationally-intact target receptors, 2) target receptors within Lipoparticles are not exposed to adjuvants or biologically destructive environments so remain structurally intact, and 3) target receptors with high sequence conservation across species can be used as targets. PUBLIC HEALTH RELEVANCE: This proposal will result in monoclonal antibodies against important membrane protein targets for therapeutic development, diagnostics, and biomedical research. Lipoparticles optimized as panning reagents will be developed as a commercial product, and Lipoparticle-derived MAbs against biomedically important membrane protein targets will be licensed for therapeutic development or diagnostic use, or enter the commercial market as research reagents.

描述（由申请人提供）：我们建议使用一种新技术，脂质体颗粒，以适合噬菌体淘选的形式捕获和浓缩结构完整的膜蛋白，用于单克隆抗体分离。使用脂质颗粒来淘选噬菌体展示文库代表了获得针对保守膜蛋白抗原的抗体的有价值的方法，因为1）脂质颗粒含有高浓度的构象完整的靶受体，2）脂质颗粒内的靶受体不暴露于佐剂或生物破坏性环境，因此保持结构完整，和3）具有跨物种的高序列保守性的靶受体可用作靶。 公共卫生关系：该提案将导致针对重要膜蛋白靶点的单克隆抗体用于治疗开发，诊断和生物医学研究。作为淘选试剂优化的脂质颗粒将作为商业产品开发，脂质颗粒衍生的抗生物医学重要膜蛋白靶点的单克隆抗体将被许可用于治疗开发或诊断用途，或作为研究试剂进入商业市场。