Creating a bioluminescent mouse model for fast screening of drugs

Abstract We propose an easy way to quickly generate reporter mice without genetic manipulation of animals for the application in the drug development The generated reporter mice performs like transgenic mice which have ubiquitously embedded reporters that are needed to monitor a particular cellular or molecular process over an extended time frame Also the attachment of reporters to mice don t interfere with naturally occurring processes This proposal aims to examine a reporter system consisting of our reporter mice and a newly discovered imaging biomarker to address the challenges in creating a universal biomarker imaging for monitoring efficacy and safety of drugs By using the new reporter system we have successfully detected dynamic cellular responses to drugs in toxicological models We expect to establish a general imaging protocol for quick assessing efficacy and toxicity of drugs through the study of this proposal Public Health Relevance The success of this proposal would bring a simple way of generating reporter mice and its related imaging technology into drug discovery to accelerate the development process The new reporter system will make it possible to fast screening of drugs in animals It will break the limitation of cell based drug testing in which the simplified cellular system hardly recapitulate the actual physiological environment and is difficult to screen against targets in the cellular microenvironment The ability to direct screening drugs in animals would significantly expend drugable targets and create more efficient therapeutics