Nature biotechnology

Targeted DNA modification triggers precise repair in bacteria and causes mutations in complex cells

Updated

Abstract

This approach enables the targeted addition of ADP-ribosyl moieties to DNA, leading to distinct editing outcomes in different organisms.

  • Base editors create precise genomic edits without causing DNA breaks but only explore a limited range of modifications.
  • The bacterial antiphage toxin DarT2 is used to append chemical groups to DNA, expanding the potential for genome editing.
  • In tested bacteria, the targeted addition of ADP-ribosyl moieties facilitates homologous recombination, allowing for flexible genome editing.
  • In yeast, plant, and human cells, the modifications result in the conversion of thymine to adenine or a mix of adenine and cytosine, with minimal insertions or deletions.
  • The method, termed append editing, provides new editing possibilities that current base editors cannot achieve.

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Full Text

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Funding

Competing interests

Competing interests: C.L.B. is a cofounder and officer of Leopard Biosciences, cofounder and scientific advisor to Locus Biosciences and scientific advisor to Benson Hill. S.P.C. and K.M.P. are cofounders and officers of Hoofprint Biome. C.P., D.G., H.V.B., S.P.C., K.V., C.Z., A.-E.S., J.M.A. and C.L.B. have filed related patent applications. J.E.C. is a cofounder and scientific advisory board member of Serac Biosciences and a scientific advisory board member of Relation Therapeutics, Hornet Therapeutics and Kano Therapeutics. The lab of J.E.C. has had funded collaborations with Allogene, Cimeio and Serac. A.-E.S. is a cofounder and scientific advisory board member of RNAConnect. The other authors declare no competing interests.
PubMed

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