ZeGenesis: an innovative CRISPR/Cas9-based platform to boost target and drug discovery in zebrafish

Flavia De Santis, Vincenzo Di Donato, Javier Terriente. ZeClinics - IGTP research centre, Barcelona (SPAIN).

ABSTRACT

In the past few years, the use of zebrafish in preclinical research has grown exponentially. The reasons for the constantly increasing success of this model lay on its intrinsic characteristics. Being a vertebrate, it shows high genetic, anatomical and physiological homology with humans. In addition, it has a very fast life cycle and quickly provides scientists a large amount of biological material. In the first phase of their extra-uterine development, zebrafish larvae are optically transparent, making them ideally suited for the in-vivo imaging of various biological processes. More recently, the implementation of CRISPR/Cas9-based techniques for targeted gene manipulation reinforced even further the use of this model in biomedical research.

By combining innovative genome editing strategies with a high-throughput imaging system, we have developed ZeGenesis, a powerful platform to support the pharmaceutical industry in their drug-discovery pipelines.

On one hand, in the phase of target validation, we can employ highly efficient gene-inactivation approaches to test and prioritize candidate genes; on the other, we can use different editing strategies to generate a disease model and screen drug libraries to evaluate, simultaneously, their safety and efficacy. The versatility of zebrafish, allows us to model a broad spectrum of pathological conditions (including cardiovascular diseases, disorders of the nervous system, metabolic diseases and oncological pathologies).

Here, we describe how zebrafish can boost the drug discovery process, allowing, at the same time, effective and reliable disease modeling and fast target validation.

ZeGenesis: an innovative CRISPR/Cas9-based platform to boost target and drug discovery in zebrafish

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