SBIR Phase I: Development of a DNA-linked Kinase Assay

The broader impact of this small business innovation research (SBIR) Phase I project is the development of a highly specific and sensitive kinase assay that can be used as a research tool to discover new therapeutic targets or a clinical diagnostic test. Kinases are involved in the dysregulation of multiple cellular processes that drive the pathogenesis of various diseases, such as cancers, diabetes, and Alzheimer’s disease. Measuring kinase activities in the early stages of various kinase-driven diseases including cancers could improve patient outcomes and reduce healthcare costs. Herein, kinase activity assays will be developed in an innovative, low-cost, high-sensitivity, and multiplexed format to improve kinase activity detection and quantification for cancer-related kinases. This approach offers a critically needed innovation that could overcome multiple barriers facing existing kinase assays and better arm scientists and clinicians to understand kinase function and for personalized treatment. The development of this assay has the potential to drive new discoveries and improve clinical care across many disease areas by enabling researchers and clinicians to detect kinase activities precisely. The proposed project addresses the unmet need for sensitive, accurate, and cost-effective methods to quantify kinase activity in disease. Current kinase assay systems lack key features required for precise measurement of disease-related kinase activities. This Phase I project aims to develop a novel DNA-based kinase assay platform that enables multiplexed quantification of kinase activities with superior sensitivity and specificity compared to existing assays. DNA-based activity assays offer advantages, including cost-effectiveness, high multiplexing ability, and sensitivity. The assay is estimated to be 10- to 100-fold cheaper than current assays due to the low cost of DNA synthesis and multiplexing capability. Successful completion of Phase I will demonstrate the feasibility of utilizing this DNA-based approach for measuring kinase activities in cancer cell lysates. Subsequent Phase II studies will validate the assay with clinical samples such as patient blood, urine, and tissues. Ultimately, this DNA-based kinase assay platform aims to enable highly sensitive kinase activity profiling that is currently unattainable. This will pave the way for assay-guided patient stratification and therapeutic development by overcoming the limitations of current kinase assays. 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.