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ABSTRACT
Introduction: In the last decade, our armamentarium of cardiovascular drug therapy has expanded significantly. Using innovative functional genomics strategies such as genome editing by CRISPR/Cas9 as well as high-throughput assays to identify bioactive small chemical compounds has significantly facilitated elaboration of the underlying pathomechanism in various cardiovascular diseases. However, despite scientific progress approvals for cardiovascular drugs has stagnated significantly compared to other fields of drug discovery and therapy during the past years.
Areas covered: In this review, the authors discuss the aspects and pitfalls during the early phase of cardiovascular drug discovery and describe the advantages of zebrafish as an in vivo organism to model human cardiovascular diseases (CVD) as well as an in vivo platform for high-throughput chemical compound screening. They also highlight the emerging, promising techniques of automated read-out systems during high-throughput screening (HTS) for the evaluation of important cardiac functional parameters in zebrafish with the potential to streamline CVD drug discovery.
Expert opinion: The successful identification of novel drugs to treat CVD is a major challenge in modern biomedical and clinical research. In this context, the definition of the etiologic fundamentals of human cardiovascular diseases is the prerequisite for an efficient and straightforward drug discovery.
Article highlights
Innovative functional genomics strategies such as genome editing by CRISPR/Cas9 have significantly facilitated elaboration of the underlying pathomechanism in various cardiovascular diseases.
The zebrafish is amenable for a broad range of forward and reverse functional genomic tools allowing to model various cardiovascular diseases.
Due to its easy handling, short reproduction cycle and uncomplex phenotypical assessment the zebrafish has emerged as a suitable tool for high-throughput in vivo drug screening.
The zebrafish combines the advantages of in vitro screens such as easy handling, cost-effectiveness and high-throughput with the holism of an entire and living organism
Computer-/robotics-assisted automated high-throughput small compound screening on zebrafish disease models will further foster the identification of disease-modifying therapeutics.
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Declaration of interest
The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Reviewer Disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.
