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Gene-edited CRISPy Critters for alcohol research

机译:用于酒精研究的基因编辑脆皮

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Genetically engineered animals are powerful tools that have provided invaluable insights into mechanisms of alcohol action and alcohol-use disorder. Traditionally, production of gene-targeted animals was a tremendously expensive, time consuming, and technically demanding undertaking. However, the recent advent of facile methods for editing the genome at very high efficiency is revolutionizing how these animals are made. While pioneering approaches to create gene-edited animals first used zinc finger nucleases and subsequently used transcription activator-like effector nucleases, these approaches have been largely supplanted in an extremely short period of time with the recent discovery and precocious maturation of the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) system. CRISPR uses a short RNA sequence to guide a non-specific CRISPR-associated nuclease (Cas) to a precise, single location in the genome. Because the CRISPR/Cas system can be cheaply, rapidly, and easily reprogrammed to target nearly any genomic locus of interest simply by recoding the sequence of the guide RNA, this gene-editing system has been rapidly adopted by numerous labs around the world. With CRISPR/Cas, it is now possible to perform gene editing directly in early embryos from every species of animals that is of interest to the alcohol field. Techniques have been developed that enable the rapid production of animals in which a gene has been inactivated (knockout) or modified to harbor specific nucleotide changes (knockins). This system has also been used to insert specific DNA sequences such as reporter or recombinase genes into specific loci of interest. Genetically engineered animals created with the CRISPR/Cas system (CRISPy Critters) are being produced at an astounding pace. Animal production is no longer a significant bottleneck to new discoveries. CRISPy animal studies are just beginning to appear in the alcohol literature, but their use is expected to explode in the near future. CRISPy mice, rats, and other model organisms are sure to facilitate advances in our understanding of alcohol-use disorder. (C) 2018 Elsevier Inc. All rights reserved.
机译:基因工程动物是强大的工具,提供了酗酒和酒精使用障碍机制的宝贵洞察力。传统上,基因靶向动物的生产是昂贵的,耗时,耗时,技术苛刻的承诺。然而,最近以非常高的效率编辑基因组的容易方法的出现正在彻底改变这些动物的制造方式。虽然创造基因编辑动物的先锋方法首先使用锌指核糖酶并随后使用转录活化剂样的效应核酸酶,但这些方法在很短的时间内被近期的群体定期发现和预先成熟的群体定期分开了很短的时间回文重复(CRISPR)系统。 CRISPR使用短的RNA序列将非特异性CRISPR相关的核酸酶(CAS)引导到基因组中的精确单个位置。由于CRISPR / CAS系统可以廉价,迅速,并且易于重新编程以仅通过重新识别引导RNA的序列来靶向几乎任何基因组轨迹,因此该基因编辑系统已被世界各地的许多实验室迅速采用。使用CRISPR / CAS,现在可以从醇田感兴趣的每种动物中直接在早期胚胎中进行基因编辑。已经开发出技术,使得能够快速生产,其中基因已灭活(敲除)或修饰以涉及特定核苷酸的变化(敲扣)。该系统也已被用于将特定的DNA序列(例如报告或重组酶基因)插入特定的目标基因座。用CRISPR / CAS系统(脆皮细菌)产生的基因工程动物正在以惊人的速度产生。动物生产不再是新发现的重要瓶颈。脆弱的动物研究刚刚开始出现在酒精文献中,但预计他们的使用将在不久的将来爆炸。脆皮老鼠,大鼠和其他模型生物肯定会促进我们对酒精使用障碍的理解的进步。 (c)2018年Elsevier Inc.保留所有权利。

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