Skip to main content

Thank you for visiting nature.com. 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.

  • Matters Arising
  • Published:

To TnpB or not TnpB? Cas12 is the answer

Nature Chemical Biology volume 19, pages 263–264 (2023)Cite this article

Subjects

An Author Correction to this article was published on 16 February 2023

The Original Article was published on 01 August 2022

arising from: Kim, D. Y. et al. ‘Hypercompact adenine base editors based on transposase B guided by engineered RNA’, Nat. Chem. Biol. 18, 1005–1013 (2022); https://doi.org/10.1038/s41589-022-01077-5

Investigation into the evolutionary history of class II CRISPR systems revealed that RNA-guided endonucleases Cas9 and Cas12 evolved from IscB and TnpB proteins, which possess surprisingly similar function to their Cas orthologs1,2,3. Kim et al. claim to have discovered and engineered one such ortholog, TnpB, for base editing applications. However, we raise an issue with this claim: their engineering efforts were applied to a bona fide Cas12f1 and not TnpB. Although TnpB proteins hold biotechnological potential as RNA-guided endonucleases, it is critical to delineate which proteins are indeed TnpB and which are Cas12 to avoid confusion in the field.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Fig. 1: Candidatus woesearchaeota-derived ‘TnpB’ is a bona fide Cas12f protein.

Data availability

All nucleotide and protein sequences presented here come from publicly available Genbank accession nos. MK005734, CP050120, CP014749 and DUFM01000066.

References

  1. Chylinski, K., Makarova, K. S., Charpentier, E. & Koonin, E. V. Classification and evolution of type II CRISPR-Cas systems. Nucleic Acids Res. 42, 6091–6105 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Altae-Tran, H. et al. The widespread IS200/IS605 transposon family encodes diverse programmable RNA-guided endonucleases. Science 374, 57–65 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Karvelis, T. et al. Transposon-associated TnpB is a programmable RNA-guided DNA endonuclease. Nature 599, 692–696 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Kim, D. Y. et al. Hypercompact adenine base editors based on transposase B guided by engineered RNA. Nat. Chem. Biol. https://doi.org/10.1038/s41589-022-01077-5 (2022).

  5. Kim, D. Y. et al. Efficient CRISPR editing with a hypercompact Cas12f1 and engineered guide RNAs delivered by adeno-associated virus. Nat. Biotechnol. 40, 94–102 (2022).

    Article  CAS  PubMed  Google Scholar 

  6. Harrington, L. B. et al. Programmed DNA destruction by miniature CRISPR-Cas14 enzymes. Science 362, 839–842 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA

    Peter H. Yoon & Jennifer A. Doudna

  2. Innovative Genomics Institute, University of California, Berkeley, CA, USA

    Peter H. Yoon, Benjamin A. Adler & Jennifer A. Doudna

  3. California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, CA, USA

    Benjamin A. Adler & Jennifer A. Doudna

  4. Environmental Genomics and Systems Biology Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA

    Benjamin A. Adler & Jennifer A. Doudna

  5. Howard Hughes Medical Institute, University of California, Berkeley, CA, USA

    Jennifer A. Doudna

  6. Department of Chemistry, University of California, Berkeley, CA, USA

    Jennifer A. Doudna

  7. MBIB Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA

    Jennifer A. Doudna

Authors
  1. Peter H. Yoon
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Benjamin A. Adler
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jennifer A. Doudna
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

P.Y., B.A.A. and J.A.D. conceived of the critique, performed the analyses and wrote the manuscript.

Corresponding author

Correspondence to Jennifer A. Doudna.

Ethics declarations

Competing interests

J.A.D. is a cofounder of Caribou Biosciences, Editas Medicine, Scribe Therapeutics, Intellia Therapeutics and Mammoth Biosciences. J.A.D. is a scientific advisory board member of Vertex, Caribou Biosciences, Intellia Therapeutics, Scribe Therapeutics, Mammoth Biosciences, Algen Biotechnologies, Felix Biosciences, The Column Group, Sixth Street and Inari. J.A.D. is a Director at Johnson & Johnson, Altos and Tempus and has research projects sponsored by AppleTree Partners and Roche. All other authors declare no competing interests.

Peer review

Peer review information

Nature Chemical Biology thanks the anonymous reviewers for their contribution to the peer review of this work.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yoon, P.H., Adler, B.A. & Doudna, J.A. To TnpB or not TnpB? Cas12 is the answer. Nat Chem Biol 19, 263–264 (2023). https://doi.org/10.1038/s41589-022-01243-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41589-022-01243-9

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing