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GENOME EDITING

Base editing goes into hyperdrive

Nature Cell Biology volume 22, pages 617–618 (2020)Cite this article

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CRISPR base editors can induce single-base-pair changes in the genome, although they are often inefficient. A study now shows that fusion of the DNA-binding domain of RAD51 to base editors enhances both the efficiency and the targeting range of optimized enzymes. These ‘hyper-editors’ offer effective tools for disease modeling and gene therapy.

Base editing is a relatively new genome-engineering technology that generates targeted single-base-pair changes without inducing double-strand breaks1,2. Base editors (BEs) consist of a DNA-modifying enzyme fused to a partially disabled Cas9 nuclease, thus facilitating chemical modifications of the nucleobases within a restricted targeting window of the Cas9-binding site. Numerous efforts have been made to optimize or expand this system, including modifications to (1) the deaminase enzyme, to increase expression and nuclear targeting, and increase or decrease the window of editing; (2) the Cas protein, to expand the range of recognized DNA motifs and restrict off-target events; or (3) the single guide RNA (sgRNA) sequence, to improve specificity and editing efficiency3,4.

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Fig. 1: Enhanced efficiency and expanded editing range of hyper-base-editing enzymes engineered to include a non-specific ssDNA-binding domain of the human RAD51 protein.

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Authors and Affiliations

  1. Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA

    Alyna Katti & Lukas E. Dow

  2. Graduate School of Medical Sciences, Weill Cornell Medicine, New York, NY, USA

    Alyna Katti & Lukas E. Dow

  3. Department of Medicine, Weill Cornell Medicine, New York, NY, USA

    Lukas E. Dow

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  1. Alyna Katti
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  2. Lukas E. Dow
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Correspondence to Lukas E. Dow.

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Competing interests

L.E.D. is an inventor on a patent that describes base-editing enzymes with increased efficiency and editing range: patent application PCT/US2019/040358 (filed 2 July 2019), international publication number WO2020/033083 (publication date 13 February 2020).

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Katti, A., Dow, L.E. Base editing goes into hyperdrive. Nat Cell Biol 22, 617–618 (2020). https://doi.org/10.1038/s41556-020-0521-0

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