Phage Display Isolation of Antibodies against Antigenically Conserved Membrane Pr

描述(由申请人提供)：我们建议使用一种新的技术，脂肪制品，来捕获和浓缩结构完整的膜蛋白，并以一种适合于噬菌体淘洗的形式进行单抗分离。利用脂质体展示文库来获得针对保守的膜蛋白抗原的抗体是一种有价值的方法，因为1)脂质体含有高度构象完整的靶受体，2)脂粒内的靶受体不暴露于佐剂或生物破坏性环境中，因此保持结构完整，以及3)跨物种具有高度序列保守性的靶受体可以被用作靶标。 公共卫生相关性：这项提议将产生针对重要膜蛋白靶标的单抗，用于治疗开发、诊断和生物医学研究。被优化为平底锅试剂的脂肪制品将被开发为商业产品，而针对生物医学上重要的膜蛋白靶标的脂肪制品衍生的单抗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。

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.