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Home Science

Precise and versatile genome editing with click editors

July 22, 2024
in Science
Precise and versatile genome editing with click editors
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Research Briefing

Published: 22 July 2024

Nature Biotechnology

(2024)Cite this article

We developed click editors, comprising HUH endonucleases, DNA-dependent DNA polymerases and CRISPR–Cas9 nickases, which together enable programmable precision genome engineering from simple DNA templates.

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Fig. 1: Click editing enzymes and mechanism.

References

Halperin, S. O. et al. CRISPR-guided DNA polymerases enable diversification of all nucleotides in a tunable window. Nature 550, 248–252 (2018). This manuscript describes the fusion of an error-prone polymerase to CRISPR–Cas9 to mutagenize specified genomic regions.

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Anzalone, A. V. et al. Search-and-replace genome editing without double-strand breaks or donor DNA. Nature 576, 149–157 (2019). This paper reports the development of prime editing, a precise genome-editing approach that uses reverse transcriptases to write specific edits into a genome.

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Levesque, S., Cosentino, A., Verma, A., Genovese, P. & Bauer, D. E. Enhancing prime editing in hematopoietic stem and progenitor cells by modulating nucleotide metabolism. Nat. Biotechnol. https://doi.org/10.1038/s41587-024-02266-4 (2024). This manuscript reports the dependence of RT-based genome editing technologies, such as prime editors, on cellular dNTP levels.

Aird, E. L. et al. Increasing Cas9-mediated homology-directed repair efficiency through covalent tethering of DNA repair template. Commun. Biol. 1, 54 (2018). This study describes the use of HUHes to recruit ssDNA templates to Cas9-mediated DNA breaks to improve homology-directed repair efficiencies.

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Liu, B. et al. Targeted genome editing with a DNA-dependent DNA polymerase and exogenous DNA-containing templates. Nat. Biotechnol. https://doi.org/10.1038/s41587-023-01947-w (2023). This paper reports the development of DNA polymerase-based editors using RNA or DNA substrates for precise genome editing.

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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: Ferreira da Silva, J. et al. Click editing enables programmable genome writing using DNA polymerases and HUH endonucleases. Nat. Biotechnol. https://doi.org/10.1038/s41587-024-02324-x (2024).

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Precise and versatile genome editing with click editors.
Nat Biotechnol (2024). https://doi.org/10.1038/s41587-024-02340-x

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Published: 22 July 2024

DOI: https://doi.org/10.1038/s41587-024-02340-x

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