Goal 3: Advance Translational Research

Advanced Models for Translational Cardiovascular Research and Drug Development

Although the study of the cardiovascular (CV) system has benefited significantly from the use of gene-targeted and transgenic mouse models, small rodents do not always accurately reflect human cardiovascular physiology. Many discoveries using mouse CVD models failed to translate into human applications.

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Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Compelling Question (CQ)

Details on the impact of addressing this CQ or CC :

Outcomes from large animal studies are likely to translate into more favorable results in human studies. Historically, some of the most significant advances in modern CV medicine are indebted to large animals.

Feasibility and challenges of addressing this CQ or CC :

Recent advances in mammalian genome projects and gene targeting technologies enable the production of large animal models. Genome information is now available for many animal species including pigs, rabbits, dogs, cats, horses and cows. Customizable nucleases, such as Zinc Finger Nuclease (ZFN), Transcription Activator-Like Effector Nuclease (TALEN), CRISPRs (clustered regularly interspaced short palindromic repeats) associated protein-9 nuclease (Cas9) has enabled the production of gene targeted animals in many of these species lacking germline transmitting embryonic stem (ES) cells, with satisfactory results. Integration of these novel knowledge and technologies in non-primate large animals will lead to production of an array of novel models of human CVD. Research in these models will help identify and establish suitable animal models that faithfully predict the outcomes in human clinical trials of new medicines and treatments. This is believed to have a major impact in the medical research field in general and significantly move cardiovascular research and drug development forward.

Name of idea submitter and other team members who worked on this idea : Eugene Chen from University of Michigan

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Idea No. 829