Zebrafish, an In Vivo Platform to Screen Drugs and Proteins for Biomedical Use

Abstract

The nearly simultaneous convergence of human genetics and advanced molecular technologies has led to an improved understanding of human diseases. At the same time, the demand for drug screening and gene function identification has also increased, albeit time- and labor-intensive. However, bridging the gap between in vitro evidence from cell lines and in vivo evidence, the lower vertebrate zebrafish possesses many advantages over higher vertebrates, such as low maintenance, high fecundity, light-induced spawning, transparent embryos, short generation interval, rapid embryonic development, fully sequenced genome, and some phenotypes similar to human diseases. Such merits have popularized the zebrafish as a model system for biomedical and pharmaceutical studies, including drug screening. Here, we reviewed the various ways in which zebrafish serve as an in vivo platform to perform drug and protein screening in the fields of rare human diseases, social behavior and cancer studies. Since zebrafish mutations faithfully phenocopy many human disorders, many compounds identified from zebrafish screening systems have advanced to early clinical trials, such as those for Adenoid cystic carcinoma, Dravet syndrome and Diamond–Blackfan anemia. We also reviewed and described how zebrafish are used to carry out environmental pollutant detection and assessment of nanoparticle biosafety and QT prolongation.

Discovery of 1-benzhydryl piperazine-based HDAC inhibitors with anticancer and antimetastatic properties against human breast cancer: synthesis, molecular modeling, in vitro and in vivo biological evaluation

“…The zebrafish has emerged as a universal biotechnological platform for effective and safe drug discovery owing to their genetic, molecular, and immunological similarity to humans, and highly correlated response to pharmaceuticals including anticancer compounds [68][69][70] . The use of this model system simplifies the path of novel bioactive compounds to clinical trials and reduce the failure of potential therapeutics at later stages of testing [71,72] . Herein, we found that none of two novel HDAC inhibitors caused lethal effect at the doses up to 100 µM after the 5-day treatment (LC 50 > 100 µM) (Fig.…”

Discovery of 1-benzhydryl piperazine-based HDAC inhibitors with anti-cancer and anti-metastatic properties against human breast cancer: synthesis, molecular modeling, in vitro and in vivo biological evaluation

“…The zebrafish has emerged as a universal biotechnological platform for effective and safe drug discovery owing to their genetic, molecular, and immunological similarity to humans, and highly correlated response to pharmaceuticals including anti-cancer compounds [51][52][53] . The use of this model system simplifies the path of novel bioactive compounds to clinical trials and reduce the failure of potential therapeutics at later stages of testing [54,55] .…”

Quantification of Idua Enzymatic Activity Combined with Observation of Phenotypic Change in Zebrafish Embryos Provide a Preliminary Assessment of Mutated idua Correlated with Mucopolysaccharidosis Type I

“…The lower vertebrate zebrafish possesses many advantages over higher vertebrates, such as low maintenance, high fecundity, light-induced spawning, transparent embryos, short generation interval, rapid embryonic development, fully sequenced genome, and some phenotypes similar to human diseases [ 14 ]. Such merits have popularized the zebrafish as a model system for biomedical and pharmaceutical studies, including drug screening [ 15 , 16 ]. Additionally, zebrafish are regarded as an important research tool for studying LSD [ 17 , 18 ].…”