Recent progress in the use of zebrafish for novel cardiac drug discovery

Mirjam Ke├čler, Wolfgang Rottbauer, Steffen Just
Expert Opinion on Drug Discovery 2015, 10 (11): 1231-41

INTRODUCTION: Cardiovascular disease is the leading cause of morbidity and mortality worldwide, thereby putting a large burden on our healthcare costs. Using both human genetic approaches, as well as forward and reverse genetic strategies in animal models, significant progress has been made to unravel the genetic and molecular etiology of human cardiovascular disease that is crucial to define novel therapeutic targets. In this context, the zebrafish has emerged as an important in vivo vertebrate animal system to study and to model human cardiovascular diseases as well as for in vivo cardiovascular drug discovery.

AREAS COVERED: This review describes the rationale for using the in vivo model system zebrafish in whole-organism-based drug discovery strategies. It also highlights recent developments in the fields of drug target identification, disease modeling, and automation of high-throughput small compound screening.

EXPERT OPINION: Novel genome-editing techniques such as the clustered regularly interspaced short palindromic repeat/Cas9 (CRISPR/Cas9) and transcription activator-like effector nuclease (TALEN) technologies allow highly efficient and reliable disease modeling in the in vivo system zebrafish. The ambition of developing personalized therapeutic options will clearly be fostered by the establishment of animal disease models that accurately simulate the patient's situation and the use of these disease models in 'next-generation' high-throughput small compound screens to define treatment options tailored to individual needs. To define suitable targets for therapeutic modulation, systems biology approaches that study complex biological systems as an integrated whole will pave the way to successful in vivo disease modeling and future drug discovery.

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