Similarly to CRISPR–Cas systems, TnpB proteins from bacterial transposons can be employed as RNA-guided endonucleases for genome editing. By combining rational protein design and machine learning, ISDra2 TnpB variants with enhanced editing efficiency and a broader targeting range were developed, along with a prediction tool to design effective guiding RNAs.
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References
Meers, C. et al. Transposon-encoded nucleases use guide RNAs to promote their selfish spread. Nature 622, 863–871 (2023). This paper describes the role of TnpA and TnpB in transposition and regulation.
Altae-Tran, H. et al. The widespread IS200/IS605 transposon family encodes diverse programmable RNA-guided endonucleases. Science 374, 57–65 (2021). This paper showcases the evolutionary relationship between TnpB and CRISPR–Cas and biochemically characterizes some of these ultracompact RNA-guided systems.
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Sasnauskas, G., Tamulaitiene, G. & Druteika, G. et al. TnpB structure reveals minimal functional core of Cas12 nuclease family. Nature 616, 384–389 (2023). Refs. 5 and 6 show the structure of the ISDra2 TnpB complex.
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This is a summary of: Marquart, K. F. et al. Effective genome editing with an enhanced ISDra2 TnpB system and deep learning-predicted ωRNAs. Nat. Methods https://doi.org/10.1038/s41592-024-02418-z (2024).
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Expanding the genome editing toolbox with designer CRISPR–Cas-like transposons. Nat Methods (2024). https://doi.org/10.1038/s41592-024-02460-x
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DOI: https://doi.org/10.1038/s41592-024-02460-x
