Combining Zebrafish and CRISPR/Cas9: Toward a More Efficient Drug Discovery Pipeline

The use of zebrafish larvae in basic and applied research has grown exponentially during the last 20 years. The reasons for this success lay in its specific experimental advantages: on the one hand, the small size, the large number of progeny and the fast life cycle greatly facilitate large-scale ap...

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Main Authors: Carles Cornet, Vincenzo Di Donato, Javier Terriente
Format: Article
Language:English
Published: Frontiers Media S.A. 2018-07-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fphar.2018.00703/full
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author Carles Cornet
Vincenzo Di Donato
Javier Terriente
author_facet Carles Cornet
Vincenzo Di Donato
Javier Terriente
author_sort Carles Cornet
collection DOAJ
description The use of zebrafish larvae in basic and applied research has grown exponentially during the last 20 years. The reasons for this success lay in its specific experimental advantages: on the one hand, the small size, the large number of progeny and the fast life cycle greatly facilitate large-scale approaches while maintaining 3Rs amenability; on the other hand, high genetic and physiological homology with humans and ease of genetic manipulation make zebrafish larvae a highly robust model for understanding human disease. Together, these advantages allow using zebrafish larvae for performing high-throughput research, both in terms of chemical and genetic phenotypic screenings. Therefore, the zebrafish larva as an animal model is placed between more reductionist in vitro high-throughput screenings and informative but low-throughput preclinical assays using mammals. However, despite its biological advantages and growing translational validation, zebrafish remains scarcely used in current drug discovery pipelines. In a context in which the pharmaceutical industry is facing a productivity crisis in bringing new drugs to the market, the combined advantages of zebrafish and the CRISPR/Cas9 system, the most powerful technology for genomic editing to date, has the potential to become a valuable tool for streamlining the generation of models mimicking human disease, the validation of novel drug targets and the discovery of new therapeutics. This review will focus on the most recent advances on CRISPR/Cas9 implementation in zebrafish and all their potential uses in biomedical research and drug discovery.
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spelling doaj.art-fb9ae8a1ef6e4c25be96eb2b2c925cf12022-12-21T20:28:36ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122018-07-01910.3389/fphar.2018.00703384372Combining Zebrafish and CRISPR/Cas9: Toward a More Efficient Drug Discovery PipelineCarles CornetVincenzo Di DonatoJavier TerrienteThe use of zebrafish larvae in basic and applied research has grown exponentially during the last 20 years. The reasons for this success lay in its specific experimental advantages: on the one hand, the small size, the large number of progeny and the fast life cycle greatly facilitate large-scale approaches while maintaining 3Rs amenability; on the other hand, high genetic and physiological homology with humans and ease of genetic manipulation make zebrafish larvae a highly robust model for understanding human disease. Together, these advantages allow using zebrafish larvae for performing high-throughput research, both in terms of chemical and genetic phenotypic screenings. Therefore, the zebrafish larva as an animal model is placed between more reductionist in vitro high-throughput screenings and informative but low-throughput preclinical assays using mammals. However, despite its biological advantages and growing translational validation, zebrafish remains scarcely used in current drug discovery pipelines. In a context in which the pharmaceutical industry is facing a productivity crisis in bringing new drugs to the market, the combined advantages of zebrafish and the CRISPR/Cas9 system, the most powerful technology for genomic editing to date, has the potential to become a valuable tool for streamlining the generation of models mimicking human disease, the validation of novel drug targets and the discovery of new therapeutics. This review will focus on the most recent advances on CRISPR/Cas9 implementation in zebrafish and all their potential uses in biomedical research and drug discovery.https://www.frontiersin.org/article/10.3389/fphar.2018.00703/fullCRISPR/Cas9drug discoveryzebrafishdisease modelphenotypic drug screeningfunctional genomics
spellingShingle Carles Cornet
Vincenzo Di Donato
Javier Terriente
Combining Zebrafish and CRISPR/Cas9: Toward a More Efficient Drug Discovery Pipeline
Frontiers in Pharmacology
CRISPR/Cas9
drug discovery
zebrafish
disease model
phenotypic drug screening
functional genomics
title Combining Zebrafish and CRISPR/Cas9: Toward a More Efficient Drug Discovery Pipeline
title_full Combining Zebrafish and CRISPR/Cas9: Toward a More Efficient Drug Discovery Pipeline
title_fullStr Combining Zebrafish and CRISPR/Cas9: Toward a More Efficient Drug Discovery Pipeline
title_full_unstemmed Combining Zebrafish and CRISPR/Cas9: Toward a More Efficient Drug Discovery Pipeline
title_short Combining Zebrafish and CRISPR/Cas9: Toward a More Efficient Drug Discovery Pipeline
title_sort combining zebrafish and crispr cas9 toward a more efficient drug discovery pipeline
topic CRISPR/Cas9
drug discovery
zebrafish
disease model
phenotypic drug screening
functional genomics
url https://www.frontiersin.org/article/10.3389/fphar.2018.00703/full
work_keys_str_mv AT carlescornet combiningzebrafishandcrisprcas9towardamoreefficientdrugdiscoverypipeline
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AT javierterriente combiningzebrafishandcrisprcas9towardamoreefficientdrugdiscoverypipeline