Generation and characterisation G-protein-coupled receptor monoclonal antibodies utilising detergent-free solubilisation

近年来，抗体作为治疗剂的发展有了显著的增长。特别的好处是它们精致的特异性，即使在密切相关的受体亚型之间也是如此，这些受体亚型共享天然激动剂的保守配体结合部位。该项目旨在与领先的制药/生物技术公司UCB合作，利用一个新的抗体生成平台来培育针对G蛋白偶联受体(GPCRs)的单抗并对其进行药理学鉴定。GPCRs是最大的膜受体家族，具有重要的药理学意义，目前约有30%-40%的药物针对这些受体；对更有效的药物的需求巨大。到目前为止，我们已经成功地针对一种A类GPCR成功地培育了抗体，并致力于从其他类型和不同类型的GPCR中提取抗体。在这个项目中，还将探索替代受体表达系统和增溶方法，涉及新型聚合物，利用最新的免洗涤剂方法。根据抗体的鉴定结果，也有可能进入活细胞的鉴定，将免疫组织化学结合到该项目中。

In recent years, there has been significant growth in the development of antibodies as therapeutic agents. Of particular benefit is their exquisite specificity, even between closely-related receptor subtypes sharing a conserved ligand binding site for the natural agonist. This project aims to utilise a novel antibody generation platform in collaboration with leading pharmaceutical/bio-technology company, UCB, to raise and pharmacologically characterise monoclonal antibodies targeting G-Protein-Coupled receptors (GPCRs). GPCRs are the largest family of membrane receptors and are of great pharmacological significance, with around 30-40% of current drugs targeting these receptors; and a huge demand for more effective medicines. We have successfully raised putative antibodies for one class A GPCR so far, and aim to raise antibodies from other classes and different types of GPCRs. Alternative receptor expression systems and solubilisation methods will also be explored during this project, involving novel polymers, utilising the latest, detergent free methods. Dependent upon characterisation outcomes of the antibodies there is also potential to move into characterisation in live cells, incorporating immunohistochemistry into the project.