Development of the next generation antibody technologies and their applications

项目摘要/摘要 抗体(免疫球蛋白)是生命科学研究中使用最广泛的生物制剂之一，并具有 是疾病诊断和治疗的主要推动力。尽管过去付出了巨大的努力， 高质量的研究抗体仍然稀少，这导致了许多 科学研究论文和与误导性文献相关的巨大成本。重大挑战 包括抗体质量差(例如，低亲和力和特异性)、批次到批次的差异以及 生产、生物工程、制造和储存。迫切需要开发新的技术 应对这些挑战并在生物医学研究和药物领域提供新应用的平台 治疗学。 骆驼单链VHH抗体或纳米抗体(NBS)是一类引人注目的新抗体 具有极高的溶解度和热稳定性的特点。我们最近开发了一种强大的 发现和鉴定高质量的抗原特异性NB曲目的流水线。这条管道有 对十几种不同结构和免疫反应的抗原进行了广泛的测试和优化。 使用这种方法，可以识别大量高质量的构象Nb结合体。 在这里，我们建议开发创新的集成技术，以彻底改变Nb的发现和 人物刻画。同时，我们热衷于应用这些方法和试剂来实现新的生物医学 发现和治疗。 下一代NB平台技术的开发将在以下方面提供许多令人兴奋的新可能性 生物医学研究、疾病诊断和治疗。

PROJECT SUMMARY/ABSTRACT Antibodies (immunoglobulins) are among the most widely used biologics for life science research and have been the major driving force for disease diagnosis and therapeutics. Despite enormous efforts in the past, high-quality research antibodies remain sparse, which have led to the poor reproducibility of numerous scientific research papers and the immense costs associated with misleading literature. Major challenges include poor quality of antibodies (e.g., low affinity and specificity), batch-to-batch variations, and difficulties in production, bioengineering, manufacturing and storage. There is a pressing need to develop new technological platforms to address these challenges and to provide new applications in biomedical research and drug therapeutics. Camelid single-chain VHH antibodies or Nanobodies (Nbs) are a compelling new class of antibodies characterized by exceptionally high solubility and thermostability. We have recently developed a robust pipeline for the discovery and characterization of high-quality antigen-specific Nb repertoires. This pipeline has been extensively tested and optimized for a dozen of antigens with different structures and immune responses. With this approach, a large cohort of high-quality conformational Nb binders can be identified. Here we propose to developing innovative integrative technologies to revolutionize Nb discovery and characterization. In parallel, we are keen to apply these methods and reagents to enable new biomedical discoveries and therapeutics. Development of the next generation Nb platform technologies will offer numerous exciting new possibilities in biomedical research, disease diagnosis and therapeutics.