The broader impact of this I-Corps program is the development of bioluminescence tools that may be applied to drug discovery and optimization, particularly for the non-invasive imaging of animals. To date, bioluminescence imaging in the pharmaceutical industry has been limited due to poor light penetrance and enzyme instability. Fundamental research has contributed to the advancement of bioluminescence imaging. The goal is to bridge the gap and expand the use of bioluminescent reporters. Specifically, the proposed technology will use biosensors for rapidly evaluating drug candidates in laboratory animals, in addition to cell cultured cells. This technology may have a significant impact on central nervous system (CNS) drug development and accelerate the optimization of drugs for brain malignancies. This tool may lead to improved compounds with better blood brain barrier (BBB) penetrance and better activity in the brain, while also preventing the testing of suboptimal compounds in human volunteers and patients.
This I-Corps project is based on the development of new drug screening platforms that enable non-invasive detection of drug activity and efficacy in living animals. Recently, bioluminescent reporters have been engineered to be brighter and red-shifted, thereby allowing deep tissue imaging of biological events. These molecular tools enable the detection of drug activity in an approach that is label-free, non-invasive, and pathway-specific. In addition, these biosensors may be used to monitor drug activity in living animals, thus circumventing the numerous limitations of terminal analyses. By evaluating targeted drug candidates in vivo, without termination, the performance and efficacy of the compounds can be more accurately appraised. This is especially valuable for optimizing molecules penetrating the central nervous system (CNS), in which the blood-brain barrier (BBB) has presented significant challenges in CNS drug development. The goal of this project is to determine the ways in which these biosensors could facilitate the rapid assessment of CNS compounds, and when these tools may have the most impact in the drug development pipeline.
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.