Our ability to edit genomes lags behind our capacity to sequence them, but the growing understanding of CRISPR biology and its application to genome, epigenome and transcriptome engineering is narrowing this gap. In this Review, we discuss recent developments of various CRISPR-based systems that can transiently or permanently modify the genome and the transcriptome. The discovery of further CRISPR enzymes and systems through functional metagenomics has meaningfully broadened the applicability of CRISPR-based editing. Engineered Cas variants offer diverse capabilities such as base editing, prime editing, gene insertion and gene regulation, thereby providing a panoply of tools for the scientific community. We highlight the strengths and weaknesses of current CRISPR tools, considering their efficiency, precision, specificity, reliance on cellular DNA repair mechanisms and their applications in both fundamental biology and therapeutics. Finally, we discuss ongoing clinical trials that illustrate the potential impact of CRISPR systems on human health.

我们编辑基因组的能力落后于我们对基因组进行测序的能力，但对 CRISPR 生物学及其在基因组、表观基因组和转录组工程中的应用的日益了解正在缩小这一差距。在这篇综述中，我们讨论了各种基于 CRISPR 的系统的最新发展，这些系统可以暂时或永久地修改基因组和转录组。通过功能宏基因组学发现更多 CRISPR 酶和系统，有意义地拓宽了基于 CRISPR 的编辑的适用性。工程化的 Cas 变体提供了多种功能，例如碱基编辑、引物编辑、基因插入和基因调控，从而为科学界提供了一整套工具。我们强调了当前 CRISPR 工具的优点和缺点，考虑到它们的效率、精确度、特异性、对细胞 DNA 修复机制的依赖及其在基础生物学和治疗学中的应用。最后，我们讨论正在进行的临床试验，这些试验说明了 CRISPR 系统对人类健康的潜在影响。