College of Life Science, Nankai University, Tianjin, China.
Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China.
Nat Commun. 2023 Jan 17;14(1):257. doi: 10.1038/s41467-023-35919-0.
Prime editing is a versatile gene editing tool that enables precise sequence changes of all types in the genome, but its application is rather limited by the editing efficiency. Here, we first apply the Suntag system to recruit the transcription factor P65 and enhance the desired editing outcomes in the prime editing system. Next, MS2 hairpins are used to recruit MS2-fused P65 and confirmed that the recruitment of the P65 protein could effectively improve the prime editing efficiency in both the PE3 and PE5 systems. Moreover, this suggests the increased editing efficiency is most likely associated with the induction of chromatin accessibility change by P65. In conclusion, we apply different systems to recruit P65 and enhance the prime editing efficiency of various PE systems. Furthermore, our work provides a variety of methods to work as protein scaffolds for screening target factors and thus supports further optimization of prime editing systems.
先导编辑是一种多功能的基因编辑工具，可实现基因组中所有类型的精确序列变化，但由于编辑效率的限制，其应用受到了限制。在这里，我们首先应用 Suntag 系统招募转录因子 P65，并增强先导编辑系统中所需的编辑效果。接下来，使用 MS2 发夹结构招募 MS2 融合的 P65，并证实 P65 蛋白的募集可以有效地提高 PE3 和 PE5 系统中的先导编辑效率。此外，这表明编辑效率的提高很可能与 P65 诱导染色质可及性改变有关。总之，我们应用不同的系统来招募 P65，并提高各种 PE 系统的先导编辑效率。此外，我们的工作为筛选靶因子提供了多种方法作为蛋白质支架，从而支持进一步优化先导编辑系统。
