Development of the next generation antibody technologies and their applications

下一代抗体技术开发及其应用

• 批准号: 10026996
• 负责人: Yi Shi
• 金额: $ 39.13万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-10 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10026996
• 关键词: Address; Affinity; Antibodies; Antigens; Biological; Biological Sciences; Biomedical Engineering; Biomedical Research; Development; Hybrids; Immune response; Immunoglobulins; Literature; Methods; Molecular Conformation; Paper; Pharmaceutical Preparations; Production; Proteomics; Reagent; Reproducibility; Research; Solubility; Specificity; Structure; Technology; Testing; Therapeutic; Variant; cohort; cost; disease diagnosis; driving force; innovation; nanobodies; next generation; thermostability

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.

项目总结/摘要 抗体（免疫球蛋白）是用于生命科学研究的最广泛使用的生物制剂之一， 是疾病诊断和治疗的主要驱动力。尽管过去付出了巨大的努力， 高质量的研究抗体仍然稀少，这导致许多抗体的重现性差。 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）、批次间的差异以及 生产、生物工程、制造和储存。迫切需要开发新的技术 平台，以应对这些挑战，并提供新的应用，在生物医学研究和药物 治疗学 骆驼科动物单链VHH抗体或纳米抗体（Nbs）是引人注目的新型抗体 其特征在于特别高的溶解度和热稳定性。我们最近开发了一个强大的 用于发现和表征高质量抗原特异性Nb库的管道。这条管道有 经过广泛的测试和优化，针对十几种具有不同结构和免疫反应的抗原。 通过这种方法，可以鉴定大量高质量构象Nb结合剂。 在这里，我们建议开发创新的综合技术，以彻底改变铌的发现， 特征化同时，我们热衷于应用这些方法和试剂，使新的生物医学 发现和治疗。 下一代Nb平台技术的开发将为未来的发展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。