Precise nucleic acid editing technologies have facilitated the research of cellular function and the development of novel therapeutics, especially the current programmable nucleases-based editing tools, such as the prokaryotic clustered regularly interspaced short palindromic repeats (CRISPR)-associated nucleases (Cas). As CRISPR-based therapies are advancing toward human clinical trials, it is important to understand how natural genetic variation in the human population may affect the results of these trials and even patient safety. The development of "base-editing" technique allows the direct, stable transformation of target DNA base into an alternative in a programmable way, without DNA double strand cleavage or a donor template. Genome-editing techniques hold promises for the treatment of genetic disease at the DNA level by blocking the sequences associated with disease from producing disease-causing proteins. Currently, scientists can select the gene they want to modify, use the Cas9 as a "molecular cutter" to cut it out, and transform it into a more desirable version. In this review, we focus on the recent advances of CRISPR/Cas system by outlining the evolutionary and biotechnological implications of current strategies for improving the specificity and accuracy of these genome-editing technologies.

中文翻译：

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基于 CRISPR 的基因组编辑回顾：生存、进化和挑战。

精确的核酸编辑技术促进了细胞功能的研究和新疗法的开发，特别是当前基于可编程核酸酶的编辑工具，例如原核成簇的规则间隔短回文重复序列（CRISPR）相关的核酸酶（Cas）。随着基于 CRISPR 的疗法向人体临床试验推进，了解人群中的自然遗传变异如何影响这些试验的结果甚至患者安全非常重要。“碱基编辑”技术的发展允许以可编程方式将目标 DNA 碱基直接、稳定地转化为替代物，而无需 DNA 双链切割或供体模板。基因组编辑技术有望通过阻断与疾病相关的序列产生致病蛋白来治疗 DNA 水平的遗传疾病。目前，科学家可以选择他们想要修改的基因，将Cas9作为“分子切割器”将其切割出来，并将其转化为更理想的版本。在这篇综述中，我们通过概述当前提高这些基因组编辑技术的特异性和准确性的策略的进化和生物技术影响，重点关注 CRISPR/Cas 系统的最新进展。