I-Corps: Heat-stable binding proteins for diverse diagnostic applications

I-Corps项目的更广泛影响/商业潜力将是使人们能够迅速开发出准确、热稳定和负担得起的新型诊断测试，从而扩大服务不足的患者群体获得医疗保健的机会。传统上，诊断性免疫分析依赖于称为抗体的结合蛋白来捕获和检测患者样本中的疾病生物标志物。高质量诊断抗体的开发和生产是缓慢而昂贵的，这类试剂经常受到热不稳定性和脱靶结合的影响，导致检测结果不准确。这个项目的重点是开发一种新型的低成本、热稳定的结合蛋白，这种蛋白可以快速开发并很容易地集成到各种诊断形式中。这些结合蛋白可以被设计成针对不同的疾病生物标志物，使该平台适合开发针对许多不同医疗条件的新型检测方法。这个I-Corps项目将探索结合蛋白在广泛诊断应用中的商业潜力。提出的模块化结合蛋白已被验证为一系列标准诊断格式和许多疾病靶点。用于开发这些新的结合蛋白的体外过程可以被很好地控制，以确保所选择的试剂具有高度的靶向特异性，并以高亲和力与感兴趣的生物标志物结合。此外，选定的试剂可以进行进一步的工程设计，以产生多功能蛋白质结构，从而实现易于制造的设备，高增益信号放大和高效的目标捕获。采用这些热稳定试剂的低成本诊断设备将能够在医疗点具有成本效益地检测疾病病例，该平台启用的新型诊断能力将解决未满足的公共卫生需求。该奖项反映了美国国家科学基金会的法定使命，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。

The broader impact/commercial potential of this I-Corps project will be to enable the rapid development of novel diagnostic tests that are accurate, thermally stable, and affordable, thereby expanding access to medical care within underserved patient populations. Diagnostic immunoassays have traditionally relied upon binding proteins called antibodies for the capture and detection of biomarkers of disease in patient samples. The development and production of high-quality diagnostic antibodies is slow and expensive, and this class of reagents is frequently subject to thermal instability and off-target binding, resulting in inaccurate test results. This project focuses on the development of a novel class of low-cost, heat-stable binding proteins that can be rapidly developed and readily integrated into various diagnostic formats. These binding proteins can be engineered to target diverse disease biomarkers, making this platform suitable for the development of novel assays addressing many different medical conditions.This I-Corps project will explore the commercial potential of using binding proteins in a broad range of diagnostic applications. The proposed modular binding proteins have been validated for a range of standard diagnostic formats and numerous disease targets. The in vitro processes used to develop these new binding proteins can be finely controlled in order to ensure that selected reagents are highly target-specific, and bind to the biomarker of interest with high affinity. In addition, selected reagents can be subjected to further engineering in order to produce multi-functional protein constructs, enabling facile device manufacturing, high-gain signal amplification, and highly efficient target capture. Low-cost diagnostic devices incorporating these heat-stable reagents will enable the cost-efficient detection of disease cases at the point-of-care, and novel diagnostic capabilities enabled by this platform will address unmet public health needs.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.