I-Corps: DNA-based kinase activity detection platform

I-Corps项目的广泛影响是改善患者的治疗效果，降低医疗保健成本，帮助制药科学家开发新疗法，并支持正在进行的阐明激酶作用机制的工作。激酶参与体内葡萄糖（糖）的代谢。目前可用的激酶活性测定系统缺乏高灵敏度，成本效益，以及在复杂介质中精确和准确地进行测量的能力。疾病的过度诊断和过度治疗是一个严重问题，导致许多患者忍受不必要的副作用，如活检引起的感染和高昂的医疗费用。提出的方法可能提供一个急需的创新，将克服现有激酶测定面临的多重障碍，更好地装备临床医生和制药科学家在治疗和开发下一代疗法。这个I-Corps项目将解决当前激酶活性测定的缺点。该项目的目标是利用创新的基于dna的蛋白质活性检测系统开发高灵敏度和多路激酶检测。基于dna的活性分析比目前的分析显示出多种优势，包括成本效益、多路复用能力、高灵敏度和特异性。由于DNA合成成本低，这种检测方法将比目前的检测方法便宜10到100倍。所提出的方法能够在临床相关生物样品中检测低至100飞摩尔（fM）的蛋白质活性。最终，这个创新的基于dna的激酶检测平台将解决当前激酶检测系统面临的局限性，提供一种新的解决方案，在疾病诊断和/或监测各种癌症的激酶靶向药物反应性方面提供高特异性、敏感性和准确性。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 of this I-Corps project is to improve patient outcomes, lower healthcare costs, aid pharmaceutical scientists in the development of new therapies, and support ongoing efforts to elucidate kinase mechanisms of action. Kinase enzymes are involved in the metabolism of glucose(sugar) in the body. Currently available kinase activity assay systems lack high sensitivity, cost-effectiveness, and the ability to make measurements in a complex media precisely and accurately. Overdiagnosis and overtreatment of disease is a critical problem that causes many patients to endure unnecessary side effects, such as infections from biopsies and high healthcare costs. The proposed approach may offer a critically needed innovation that will overcome multiple barriers facing existing kinase assays and better equip clinicians and pharmaceutical scientists in the treatment and development of next generation therapies.This I-Corps project will address drawbacks of current kinase activity assays. The goal of this project is to develop highly sensitive and multiplexed kinase assays using an innovative DNA-based protein activity detection system. DNA-based activity assays display multiple advantages over current assays, including cost effectiveness, multiplexing ability, high sensitivity, and specificity. This assay will be 10- to 100-fold cheaper than current assays due to the low cost of DNA synthesis. The proposed approach enables the detection of protein activities as low as 100 femtomolar (fM) in proteins in clinically-relevant biological samples. Ultimately, this innovative DNA-based kinase assay platform will address the limitations facing current kinase assay systems with a new solution that offers high specificity, sensitivity, and accuracy in terms of disease diagnostics and/or monitoring the kinase targeted drug responsiveness of various cancers.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.