Screening and implementing universal ligands for immunoglobulins

免疫球蛋白通用配体的筛选和实施

• 批准号: 1829137
• 负责人: Valeria Milam
• 金额: $ 34.5万
• 依托单位: Georgia Tech Research Corporation
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1829137&HistoricalAwards=false
• 关键词: Screening; implementing; universal; ligands; immunoglobulins

The human body produces antibodies, also known as immunoglobulins, to recognize and respond to specific pathogens, including bacteria and viruses. Synthetic production of high quality antibodies is a means to treat disease via immunotherapy. The use of synthetic antibodies in commercial kits continues to grow. The handling and purification of antibodies is thus crucial to commercial manufacturing of therapeutics. Current technology uses bacteria-derived proteins that bind to the antibodies as a means to capture and purify the antibody. However, these proteins are costly and the process typically requires harsh chemical solvents. In certain cases, the harsh chemicals lead to irreversible damage of the desired antibody product. This project seeks to develop DNA-derived molecules (oligonucleotides) that have programmable antibody capture and release, yet do not compromise the therapeutic function of the antibodies, and employ environmentally-friendly processing steps. This project strives to identify and implement oligonucleotide-based ligands for antibody capture. Trainees on this project will employ a multidisciplinary approach spanning engineering, biology, and immunology to both (i) screen and identify effective antibody-binding ligands that do not compromise antibody quality and (ii) discover structure-binding relationships in the ligand-antibody systems that can, in turn, inform screening efforts. Successful identification and implementation of these ligands or affinity reagents for immunologlobulins address a growing demand for identifying new, robust, cost-effective and sustainable technological approaches. Moreover, these oligonucleotide-based ligands can potentially shorten the time-to-market for the ever expanding supply of new polyclonal, monoclonal, and modified antibodies.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

人体产生抗体，也称为免疫球蛋白，以识别并应对包括细菌和病毒在内的特定病原体。高质量抗体的合成生产是通过免疫疗法治疗疾病的一种手段。在商业套件中使用合成抗体的使用继续增长。因此，抗体的处理和纯化对于治疗剂的商业制造至关重要。当前的技术使用细菌衍生的蛋白质与抗体结合的蛋白质作为捕获和纯化抗体的一种手段。但是，这些蛋白质成本很高，通常需要严格的化学溶剂。在某些情况下，苛刻的化学物质会导致所需抗体产物的不可逆损害。 该项目旨在开发具有可编程抗体捕获和释放的DNA衍生分子（寡核苷酸），但不会损害抗体的治疗功能，并采用环保的处理步骤。该项目努力识别和实施基于寡核苷酸的配体以捕获抗体。该项目的受训者将采用跨越工程，生物学和免疫学的多学科方法（i）筛选并识别不损害抗体质量的有效抗体结合配体，并且（ii）发现配体抗体系统中的结构结合关系反过来，这可以为筛查工作提供信息。成功识别和实施这些配体或亲和力试剂的免疫球蛋白解决了人们对识别新的，健壮，成本效益和可持续技术方法的日益增长的需求。此外，这些基于寡核苷酸的配体可能会缩短新的多克隆，单克隆和修改的抗体的不断扩大的市场时间。该奖项反映了NSF的法定任务，并通过使用该基金会的智力来支持NSF的法定任务。优点和更广泛的影响审查标准。