Generation of a more efficient prime editor 2 by addition of the Rad51 DNA-binding domain

Myungjae Song, Jung Min Lim, Seonwoo Min, Jeong Seok Oh, Dong Young Kim, Jae Sung Woo, Hiroshi Nishimasu, Sung Rae Cho, Sungroh Yoon, Hyongbum Henry Kim

Research output: Contribution to journalArticlepeer-review

42 Citations (Scopus)

Abstract

Although prime editing is a promising genome editing method, the efficiency of prime editor 2 (PE2) is often insufficient. Here we generate a more efficient variant of PE2, named hyPE2, by adding the Rad51 DNA-binding domain. When tested at endogenous sites, hyPE2 shows a median of 1.5- or 1.4- fold (range, 0.99- to 2.6-fold) higher efficiencies than PE2; furthermore, at sites where PE2-induced prime editing is very inefficient (efficiency < 1%), hyPE2 enables prime editing with efficiencies ranging from 1.1% to 2.9% at up to 34% of target sequences, potentially facilitating prime editing applications.

Original languageEnglish
Article number5617
JournalNature communications
Volume12
Issue number1
DOIs
Publication statusPublished - 2021 Dec 1

Bibliographical note

Funding Information:
We would like to thank Sehyuk Kwon and Jinman Park for helping with computational analyses. We are grateful to Madeleine Doekyong Lee, Seonmi Park, and Younghye Kim for assisting with the experiments. We thank Hui Kwon Kim and Goosang Yu for providing primers and technical comments. This work was supported in part by the National Research Foundation of Korea (grants 2017R1A2B3004198 (H.H.K.), 2017M3A9B4062403 (H.H.K.), and 2018R1A5A2025079 (H.H.K.)), Brain Korea 21 Four Project for Medical Sciences (Yonsei University College of Medicine), and the Korean Health Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (grant HI17C0676 (H.H.K.)).

Publisher Copyright:
© 2021, The Author(s).

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry,Genetics and Molecular Biology
  • General
  • General Physics and Astronomy

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