Biological Engineering Program, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
Center for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114, United States.
Biochemistry. 2023 Dec 19;62(24):3493-3499. doi: 10.1021/acs.biochem.2c00311. Epub 2022 Sep 1.
Genome editing approaches have transformed the ability to make user-defined changes to genomes in both and contexts. Despite the abundant development of technologies that permit the installation of nucleotide-level changes, until recently, larger-scale sequence edits via technologies independent of DNA double-strand breaks (DSBs) had remained less explored. Here, we review recent advances toward DSB-free technologies that enable kilobase-scale modifications including insertions, deletions, inversions, replacements, and others. These technologies provide new capabilities for users, while offering hope for the simplification of putative therapeutic strategies by moving away from small mutation-specific edits and toward more generalizable kilobase-scale approaches.
基因组编辑方法改变了在 和 两种背景下对基因组进行用户定义的改变的能力。尽管有大量技术可以实现核苷酸水平的改变,但直到最近,通过独立于 DNA 双链断裂 (DSB) 的技术进行更大规模的序列编辑仍然较少被探索。在这里,我们回顾了最近在无 DSB 技术方面的进展,这些技术可以实现千碱基级别的修饰,包括插入、缺失、倒位、替换等。这些技术为用户提供了新的功能,同时也为通过从特定小突变编辑转向更具通用性的千碱基级方法来简化潜在的治疗策略提供了希望。