Explore the dominant factor in prime editing via a view of DNA processing

Zhimeng Xu; Dacheng Ma; Houzhen Su; Xiaodong Jia; Yinqing Li; Yinying Lu; Zhen Xie

doi:10.1016/j.synbio.2023.05.007

Explore the dominant factor in prime editing via a view of DNA processing

Synth Syst Biotechnol. 2023 Jun 3;8(3):371-377. doi: 10.1016/j.synbio.2023.05.007. eCollection 2023 Sep.

Authors

Zhimeng Xu¹, Dacheng Ma², Houzhen Su¹, Xiaodong Jia³, Yinqing Li⁴, Yinying Lu³, Zhen Xie¹

Affiliations

¹ MOE Key Laboratory of Bioinformatics and Bioinformatics Division, Center for Synthetic and System Biology, Department of Automation, Beijing National Research Center for Information Science and Technology, Tsinghua University, Beijing, 100084, China.
² Research Center for Biological Computation, Zhejiang Laboratory, Hangzhou, 311100, China.
³ Comprehensive Liver Cancer Centre, The Fifth Medical Center of PLA General Hospital, Beijing, China.
⁴ School of Pharmaceutical Sciences, IDG/McGovern Institute for Brain Research, Tsinghua University, Beijing, China.

Abstract

Prime editing is a revolutionary gene-editing method that is capable of introducing insertions, deletions and base substitutions into the genome. However, the editing efficiency of Prime Editor (PE) is limited by the DNA repair process. Here, we show that overexpression of the flap structure-specific endonuclease 1 (FEN1) and the DNA ligase 1 (LIG1) increases the efficiency of prime editing, which is similar to the dominant negative mutL homolog 1 (MLH1dn). In addition, MLH1 is still the dominant factor over FEN1 and LIG1 in prime editing. Our results help to further understand the relationship of proteins involved in prime editing and envisage future directions for the development of PE.