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 dont 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 Statement: 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.
Project Terms: Acute; Address; Animal Model; Animals; base; Biological Markers; Biological Process; Cells; Development; dosage; Dose; drug development; drug discovery; Drug effect disorder; Drug Targeting; drug testing; Drug toxicity; efficacy evaluation; Environment; experimental study; Extracellular Matrix; Frequencies; genetic manipulation; Image; imaging biomarker; Imaging technology; Intervention; Luminescent Proteins; Modeling; Molecular; Monitor; mouse model; Mus; Pharmaceutical Preparations; Pharmacotherapy; Physiological; Preclinical Drug Evaluation; Process; Protocols documentation; public health relevance; Reporter; response; Safety; success; System; Testing; Therapeutic; Time; tool; Toxic effect; Toxicology; Transgenic Mice
