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Genetic engineering

Novel recombinases for large DNA insertions

Nature Biotechnology (2022)Cite this article

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Bioinformatic mining and engineering of serine recombinases yields improved genome editing tools.

Despite the surge of genome engineering tools reported in the past decade, researchers still lack reliable methods for precise insertion of large DNA sequences. Editing strategies that employ CRISPR RNA-guided nucleases to cause DNA double-strand breaks rely on complex cellular DNA repair pathways, cause heterogeneity in editing byproducts, and trigger aberrant chromosomal deletions and translocations1,2. Base editors and prime editors achieve higher product purity without double-strand break intermediates, but are largely restricted to insertions smaller than 50 base pairs. New reports in Nature Biotechnology by Durrant et al.3 and Yarnall et al.4 address this gap using phage-derived large serine recombinases (LSRs) for predictable genomic insertion of large DNA cargoes, highlighting the engineering opportunities afforded by an expert combination of bioinformatics and experimental approaches.

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Fig. 1: Improved tools for large-scale DNA insertions using large serine recombinases (LSRs).

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY, USA

    George D. Lampe & Samuel H. Sternberg

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  1. George D. Lampe
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  2. Samuel H. Sternberg
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Correspondence to Samuel H. Sternberg.

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Competing interests

S.H.S. is a co-founder and scientific advisor to Dahlia Biosciences, a scientific advisor to Prime Medicine and CrisprBits, and an equity holder in Dahlia Biosciences and CrisprBits.

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Lampe, G.D., Sternberg, S.H. Novel recombinases for large DNA insertions. Nat Biotechnol (2022). https://doi.org/10.1038/s41587-022-01600-y

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