CRISPR-Cas 介导的转录调控：CRISPRa 和 CRISPRi 的治疗潜力。
CRISPR-Cas-mediated transcriptional modulation: The therapeutic promises of CRISPRa and CRISPRi.
机构信息
Department of Biomedicine, Aarhus University, 8000 Aarhus C, Denmark.
Department of Biomedicine, Aarhus University, 8000 Aarhus C, Denmark.
出版信息
Mol Ther. 2023 Jul 5;31(7):1920-1937. doi: 10.1016/j.ymthe.2023.03.024. Epub 2023 Mar 24.
The CRISPR-Cas system is commonly known for its ability to cleave DNA in a programmable manner, which has democratized gene editing and facilitated recent breakthroughs in gene therapy. However, newer iterations of the technology using nuclease-disabled Cas enzymes have spurred a variety of different types of genetic engineering platforms such as transcriptional modulation using the CRISPR activation (CRISPRa) and CRISPR interference (CRISPRi) systems. This review introduces the creation of these programmable transcriptional modulators, various methods of delivery utilized for these systems, and recent technological developments. CRISPRa and CRISPRi have also been implemented in genetic screens for interrogating gene function and discovering genes involved in various biological pathways. We describe recent compelling examples of how these tools have become powerful means to unravel genetic networks and uncovering important information about devastating diseases. Finally, we provide an overview of preclinical studies in which transcriptional modulation has been used therapeutically, and we discuss potential future directions of these novel modalities.
CRISPR-Cas 系统以其可编程切割 DNA 的能力而广为人知，这使得基因编辑民主化，并促进了基因治疗的最新突破。然而，使用核酸酶失活 Cas 酶的新技术催生了各种不同类型的基因工程平台，如使用 CRISPR 激活（CRISPRa）和 CRISPR 干扰（CRISPRi）系统的转录调节。本综述介绍了这些可编程转录调节剂的创建、用于这些系统的各种递送方法以及最近的技术发展。CRISPRa 和 CRISPRi 也已用于遗传筛选，以研究基因功能并发现涉及各种生物途径的基因。我们描述了最近引人注目的例子，说明这些工具如何成为揭示遗传网络和发现关于毁灭性疾病的重要信息的有力手段。最后，我们概述了转录调节在治疗中的临床前研究，并讨论了这些新型模式的潜在未来方向。
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