Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Research Briefing
  • Published:

Capturing prime editor off-target sites within the genome

Prime editing systems hold tremendous promise for the precise correction of pathogenic mutations. We developed a method to tag sequences modified by a prime editor to evaluate its genome-wide precision for therapeutic applications.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Schematic overview of in vitro PE-tag.


  1. Anzalone, A. V. et al. Search-and-replace genome editing without double-strand breaks or donor DNA. Nature 576, 149–157 (2019). This paper is the original description of a Cas9-based prime editing system.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Giannoukos, G. et al. UDiTaS, a genome editing detection method for indels and genome rearrangements. BMC Genomics 19, 212 (2018). This paper reports the UMI-based Tn5 tagmentation methodology.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Tsai, S. Q. et al. GUIDE-seq enables genome-wide profiling of off-target cleavage by CRISPR-Cas nucleases. Nat. Biotechnol. 33, 187–197 (2015). This paper reports the GUIDE-seq method to capture Cas9 nuclease-based off-target sites genome-wide.

    Article  CAS  PubMed  Google Scholar 

  4. Kim, D. Y., Moon, S. B., Ko, J. H., Kim, Y. S. & Kim, D. Unbiased investigation of specificities of prime editing systems in human cells. Nucleic Acids Res 48, 10576–10589 (2020). This paper reports a nickase-based Digenome-seq (nDigenome-seq) approach to identify single-strand breaks induced by Cas9 H840A nickase.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Petri, K. et al. CRISPR prime editing with ribonucleoprotein complexes in zebrafish and primary human cells. Nat. Biotechnol. 40, 189–193 (2021). This paper reports prime editing with purified prime editor protein.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This is a summary of: Liang, S.-Q. et al. Genome-wide profiling of prime editor off-target sites in vitro and in vivo using PE-tag. Nat. Methods (2023)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Capturing prime editor off-target sites within the genome. Nat Methods 20, 801–802 (2023).

Download citation

  • Published:

  • Issue Date:

  • DOI:


Quick links

Nature Briefing: Translational Research

Sign up for the Nature Briefing: Translational Research newsletter — top stories in biotechnology, drug discovery and pharma.

Get what matters in translational research, free to your inbox weekly. Sign up for Nature Briefing: Translational Research