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转录激活样效应因子核酸酶(TALENs)和规律成簇间隔短回文重复序列/CRISPR相关蛋白9(CRISPR/Cas9)助力构建具有临床相关性的非洲爪蟾基因工程肿瘤模型。

TALENs and CRISPR/Cas9 fuel genetically engineered clinically relevant Xenopus tropicalis tumor models.

作者信息

Naert Thomas, Van Nieuwenhuysen Tom, Vleminckx Kris

机构信息

Developmental Biology Unit, Department of Biomedical Molecular Biology, Ghent University, Belgium.

Center for Medical Genetics, Ghent University and Ghent University Hospital, Belgium.

出版信息

Genesis. 2017 Jan;55(1-2). doi: 10.1002/dvg.23005.

Abstract

The targeted nuclease revolution (TALENs, CRISPR/Cas9) now allows Xenopus researchers to rapidly generate custom on-demand genetic knockout models. These novel methods to perform reverse genetics are unprecedented and are fueling a wide array of human disease models within the aquatic diploid model organism Xenopus tropicalis (X. tropicalis). This emerging technology review focuses on the tools to rapidly generate genetically engineered X. tropicalis models (GEXM), with a focus on establishment of genuine genetic and clinically relevant cancer models. We believe that due to particular advantageous characteristics, outlined within this review, GEXM will become a valuable alternative animal model for modeling human cancer. Furthermore, we provide perspectives of how GEXM will be used as a platform for elucidation of novel therapeutic targets and for preclinical drug validation. Finally, we also discuss some future prospects on how the recent expansions and adaptations of the CRISPR/Cas9 toolbox might influence and push forward X. tropicalis cancer research.

摘要

靶向核酸酶革命(转录激活样效应因子核酸酶、规律成簇间隔短回文重复序列/CRISPR相关蛋白9)现在使非洲爪蟾研究人员能够快速生成定制的按需基因敲除模型。这些进行反向遗传学研究的新方法是前所未有的,正在推动水生二倍体模式生物热带爪蟾(X. tropicalis)中广泛的人类疾病模型的建立。这篇新兴技术综述聚焦于快速生成基因工程热带爪蟾模型(GEXM)的工具,重点是建立真正的遗传和临床相关癌症模型。我们认为,由于本综述中概述的特殊优势特征,GEXM将成为用于模拟人类癌症的有价值的替代动物模型。此外,我们阐述了GEXM将如何用作阐明新治疗靶点和进行临床前药物验证的平台。最后,我们还讨论了CRISPR/Cas9工具箱最近的扩展和改编可能如何影响和推动热带爪蟾癌症研究的一些未来前景。

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