4.8 Article

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

Journal

NATURE COMMUNICATIONS
Volume 12, Issue 1, Pages -

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41467-021-25928-2

Keywords

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Funding

  1. National Research Foundation of Korea [2017R1A2B3004198, 2017M3A9B4062403, 2018R1A5A2025079]
  2. Brain Korea 21 Four Project for Medical Sciences (Yonsei University College of Medicine)
  3. Korean Health Technology RAMP
  4. D Project, Ministry of Health and Welfare, Republic of Korea [HI17C0676]
  5. National Research Foundation of Korea [2017M3A9B4062403, 2017R1A2B3004198, 2018R1A5A2025079] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)

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By fusing a Rad51 DNA-binding domain, researchers have created hyPE2 with improved editing efficiency compared to PE2.
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. While prime editing is a promising technology, PE2 systems often have low efficiency. Here the authors fuse a Rad51 DNA-binding domain to create hyPE2 with improved editing efficiency.

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