Authors: Guiquan Zhang, Yao Liu, Shisheng Huang, Shiyuan Qu, Daolin Cheng, Yuan Yao, Quanjiang Ji, Xiaolong Wang, Xingxu Huang, Jianghuai Liu
Published: 2022-04-06
DOI: 10.1038/s41467-022-29507-x
Source: Full article
AbstractThe prime editors (PEs) have shown great promise for precise genome modification. However, their suboptimal efficiencies present a significant technical challenge. Here, by appending a viral exoribonuclease-resistant RNA motif (xrRNA) to the 3′-extended portion of pegRNAs for their increased resistance against degradation, we develop an upgraded PE platform (xrPE) with substantially enhanced editing efficiencies in multiple cell lines. A pan-target average enhancement of up to 3.1-, 4.5- and 2.5-fold in given cell types is observed for base conversions, small deletions, and small insertions, respectively. Additionally, xrPE exhibits comparable edit:indel ratios and similarly minimal off-target editing as the canonical PE3. Of note, parallel comparison of xrPE to the most recently developed epegRNA-based PE system shows their largely equivalent editing performances. Our study establishes a highly adaptable platform of improved PE that shall have broad implications.