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，以识别和应对特定的病原体，包括细菌和病毒。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。合成抗体在商业试剂盒中的使用持续增长。因此，抗体的处理和纯化对于治疗剂的商业制造至关重要。目前的技术使用与抗体结合的细菌衍生蛋白作为捕获和纯化抗体的手段。然而，这些蛋白质是昂贵的，并且该过程通常需要苛刻的化学溶剂。在某些情况下，刺激性化学品导致所需抗体产物的不可逆损伤。 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），但不损害抗体的治疗功能，并采用环境友好的加工步骤。该项目致力于识别和实现基于抗生物素肽的抗体捕获配体。该项目的学员将采用跨工程学，生物学和免疫学的多学科方法，以（i）筛选和鉴定不影响抗体质量的有效抗体结合配体，以及（ii）发现配体-抗体系统中的结构结合关系，从而为筛选工作提供信息。这些免疫球蛋白的配体或亲和试剂的成功鉴定和实施解决了对鉴定新的、稳健的、具有成本效益的和可持续的技术方法的日益增长的需求。此外，这些基于多核苷酸的配体可以潜在地缩短新的多克隆、单克隆和修饰抗体不断扩大的供应的上市时间。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。