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:

Mis-annotation of TnpB: case of TaRGET-ABE

Nature Chemical Biology volume 19, pages 261–262 (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

Adeno associated viruses (AAVs) are preferable delivery vehicles of genome editing tools for human therapeutic applications. However, due to their cargo packing limit, more compact genome editors are highly desirable. In a recent study published in Nature Chemical Biology, Kim et al.1 reported engineering of the AAV-compatible hypercompact base editors using the scaffold of the TnpB protein in what is the smallest genome editing platform known so far2,3. We re-analyzed the Kim et al.1 study data and argue that the hypercompact base editor described in that paper is based on the Cas12f1 protein of the type V CRISPR-Cas antiviral defense system, and not on the transposase accessory protein TnpB as is claimed in the paper. In conclusion, these results indicate that in addition to the phylogenetic analysis, the adjacent genomic context should be taken into consideration to avoid mis-annotation of miniature nucleases, which in this case lead to mis-naming of the UnCas12f1 protein of the type V CRISPR-Cas system as TnpB.

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: Genomic architectures of IS200/IS605 MGEs and CRISPR-Cas12f systems.

References

  1. 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).

  2. 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 

  3. Altae-Tran, H. et al. The widespread IS200/605 transposon family encodes diverse programmable RNA-guided endonucleases. Science https://doi.org/10.1126/science.abj6856 (2021).

  4. He, S. et al. The IS200/IS605 family and ‘peel and paste’ single-strand transposition mechanism. Microbiol. Spectr. https://doi.org/10.1128/microbiolspec.MDNA3-0039-2014 (2015).

  5. Wang, J. Y., Pausch, P. & Doudna, J. A. Structural biology of CRISPR-Cas immunity and genome editing enzymes. Nat. Rev. Microbiol. 20, 641–656 (2022).

    Article  CAS  PubMed  Google Scholar 

  6. Kim, D. Y. et al. Efficient CRISPR editing with a hypercompact Cas12f1 and engineered guide RNAs delivered by adeno-associated virus. Nat. Biotechnol. https://doi.org/10.1038/s41587-021-01009-z (2021).

  7. Wu, Z. et al. Programmed genome editing by a miniature CRISPR-Cas12f nuclease. Nat. Chem. Biol. https://doi.org/10.1038/s41589-021-00868-6 (2021).

  8. Xu, X. et al. Engineered miniature CRISPR-Cas system for mammalian genome regulation and editing. Mol. Cell https://doi.org/10.1016/j.molcel.2021.08.008 (2021).

  9. Bigelyte, G. et al. Miniature type V-F CRISPR-Cas nucleases enable targeted DNA modification in cells. Nat. Commun. 12, 6191 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  10. 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 

  11. Karvelis, T. et al. PAM recognition by miniature CRISPR–Cas12f nucleases triggers programmable double-stranded DNA target cleavage. Nucleic Acids Res. 48, 5016–5023 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Altschul, S. F. et al. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 25, 3389–3402 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Makarova, K. S. et al. Evolutionary classification of CRISPR-Cas systems: a burst of class 2 and derived variants. Nat. Rev. Microbiol. 18, 67–83 (2020).

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Biotechnology, Life Sciences Center, Vilnius University, Vilnius, Lithuania

    Tautvydas Karvelis & Virginijus Siksnys

Authors
  1. Tautvydas Karvelis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Virginijus Siksnys
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

T.K. performed the sequence analysis. T.K. and V.S. wrote the manuscript.

Corresponding authors

Correspondence to Tautvydas Karvelis or Virginijus Siksnys.

Ethics declarations

Competing interests

T.K. and V.S. are co-inventors on a patent application (PCT/IB2021/055958) filed by Vilnius University. V.S. is a chairman of and has financial interest in CasZyme.

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

Karvelis, T., Siksnys, V. Mis-annotation of TnpB: case of TaRGET-ABE. Nat Chem Biol 19, 261–262 (2023). https://doi.org/10.1038/s41589-022-01242-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41589-022-01242-w

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