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神经科学家的 CRISPR 技术。

CRISPR for neuroscientists.

机构信息

Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, 4058 Basel, Switzerland; Novartis Institutes for BioMedical Research, 4056 Basel, Switzerland.

Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, 4058 Basel, Switzerland; Department of Chemistry, University of Basel, Petersplatz 1, 4003 Basel, Switzerland; NCCR MSE, Mattenstrasse 24a, 4058 Basel, Switzerland; Botnar Research Center for Child Health, Mattenstrasse 24a, 4058 Basel, Switzerland.

出版信息

Neuron. 2023 Aug 2;111(15):2282-2311. doi: 10.1016/j.neuron.2023.04.021. Epub 2023 May 17.

Abstract

Genome engineering technologies provide an entry point into understanding and controlling the function of genetic elements in health and disease. The discovery and development of the microbial defense system CRISPR-Cas yielded a treasure trove of genome engineering technologies and revolutionized the biomedical sciences. Comprising diverse RNA-guided enzymes and effector proteins that evolved or were engineered to manipulate nucleic acids and cellular processes, the CRISPR toolbox provides precise control over biology. Virtually all biological systems are amenable to genome engineering-from cancer cells to the brains of model organisms to human patients-galvanizing research and innovation and giving rise to fundamental insights into health and powerful strategies for detecting and correcting disease. In the field of neuroscience, these tools are being leveraged across a wide range of applications, including engineering traditional and non-traditional transgenic animal models, modeling disease, testing genomic therapies, unbiased screening, programming cell states, and recording cellular lineages and other biological processes. In this primer, we describe the development and applications of CRISPR technologies while highlighting outstanding limitations and opportunities.

摘要

基因组工程技术为理解和控制健康和疾病中遗传元件的功能提供了一个切入点。微生物防御系统 CRISPR-Cas 的发现和发展产生了丰富的基因组工程技术,并彻底改变了生物医学科学。该系统由多样化的 RNA 指导酶和效应蛋白组成,这些酶和蛋白经过进化或工程设计,可用于操纵核酸和细胞过程,为生物学提供了精确的控制。几乎所有的生物系统都可以进行基因组工程——从癌细胞到模式生物的大脑,再到人类患者——这激发了研究和创新,并为健康带来了深刻的见解和治疗疾病的强大策略。在神经科学领域,这些工具正在广泛的应用中得到利用,包括工程传统和非传统的转基因动物模型、疾病建模、测试基因组疗法、无偏筛选、编程细胞状态以及记录细胞谱系和其他生物过程。在这个简介中,我们描述了 CRISPR 技术的发展和应用,同时强调了突出的局限性和机遇。

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