Petrova Irina O, Smirnikhina Svetlana A
Laboratory of Genome Editing, Research Center for Medical Genetics, Moskvorechye 1, 115478 Moscow, Russia.
Int J Mol Sci. 2025 Apr 11;26(8):3596. doi: 10.3390/ijms26083596.
Prime editing is a method of genome editing based on reverse transcription. Recent results have shown its elevated efficiency in dividing cells, which raises some questions regarding the mechanism of this effect, because prime editing does not employ homology-driven repair. This mini review aims to identify the reason for this phenomenon and find a possible solution to the problems that it poses. In dividing cells, prime editing takes advantage of high levels of dNTPs and active endonuclease and ligase machinery, such as FEN1 endonuclease and LIG1 ligase, but DNA mismatch repair, which is closely associated with replication, works against prime editing. Prime editing is a method which relies on retroviral reverse transcription, so mechanisms of intrinsic anti-retroviral defense should also work against editing. One of the factors which drastically reduce the efficiency of reverse translation is SAMHD1, which maintains low levels of dNTPs in non-dividing cells. Recent works aimed at the mitigation of SAMHD1 function demonstrated a significant increase in prime editing efficiency.
碱基编辑是一种基于逆转录的基因组编辑方法。最近的研究结果表明，它在分裂细胞中的效率有所提高，这引发了一些关于这种效应机制的问题，因为碱基编辑并不采用同源驱动修复。本综述旨在找出这一现象的原因，并找到解决其带来问题的可能方案。在分裂细胞中，碱基编辑利用了高水平的脱氧核糖核苷酸三磷酸（dNTPs）以及活跃的核酸内切酶和连接酶机制，如FEN1核酸内切酶和LIG1连接酶，但与复制密切相关的DNA错配修复却对碱基编辑起反作用。碱基编辑是一种依赖逆转录病毒逆转录的方法，因此内在的抗逆转录病毒防御机制也应对编辑起作用。大幅降低逆转录效率的因素之一是SAMHD1，它在非分裂细胞中维持低水平的dNTPs。最近旨在减轻SAMHD1功能的研究表明，碱基编辑效率显著提高。
