Based on engineered or bacterial nucleases, the development of genome editing technologies has opened up the possibility of directly targeting and modifying genomic sequences in almost all eukaryotic cells. Genome editing has extended our ability to elucidate the contribution of genetics to disease by promoting the creation of more accurate cellular and animal models of pathological processes and has begun to show extraordinary potential in a variety of fields, ranging from basic research to applied biotechnology and biomedical research. Recent progress in developing programmable nucleases, such as zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeat (CRISPR)-Cas-associated nucleases, has greatly expedited the progress of gene editing from concept to clinical practice. Here, we review recent advances of the three major genome editing technologies (ZFNs, TALENs, and CRISPR/Cas9) and discuss the applications of their derivative reagents as gene editing tools in various human diseases and potential future therapies, focusing on eukaryotic cells and animal models. Finally, we provide an overview of the clinical trials applying genome editing platforms for disease treatment and some of the challenges in the implementation of this technology.

中文翻译：

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基因组编辑技术在人类疾病靶向治疗中的应用：机制、进展与展望。

基于工程核酸酶或细菌核酸酶，基因组编辑技术的发展开辟了直接靶向和修改几乎所有真核细胞基因组序列的可能性。基因组编辑通过促进创建更准确的病理过程细胞和动物模型，扩展了我们阐明遗传学对疾病的贡献的能力，并开始在基础研究、应用生物技术和生物医学等各个领域显示出非凡的潜力。研究。最近在开发可编程核酸酶方面取得的进展，例如锌指核酸酶（ZFN）、类转录激活因子效应核酸酶（TALEN）和成簇规则间隔短回文重复序列（CRISPR）-Cas相关核酸酶，极大地加快了基因编辑的进展从概念到临床实践。在此，我们回顾了三大基因组编辑技术（ZFN、TALEN和CRISPR/Cas9）的最新进展，并讨论了它们的衍生试剂作为基因编辑工具在各种人类疾病和潜在的未来治疗中的应用，重点关注真核细胞和动物楷模。最后，我们概述了应用基因组编辑平台进行疾病治疗的临床试验以及实施该技术的一些挑战。