Programmable base editing of A•T to G•C in genomic DNA without DNA cleavage

Nicole M. Gaudelli, Alexis C. Komor, Holly A. Rees, David R. Liu · Full author list: Nicole M. Gaudelli, Alexis C. Komor, Holly A. Rees, Michael S. Packer, Ahmed H. Badran, David I. Bryson, David R. Liu.

Published 25 October 2017 · Nature · Journal article

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Summary

This work developed adenine base editors (ABEs) by evolving a transfer RNA adenosine deaminase to act on DNA, enabling direct conversion of A-T base pairs to G-C in genomic DNA without double-strand breaks. Because no natural DNA adenosine deaminase was available, the authors used directed evolution to create the enzyme, then fused it to Cas9 nickase. ABEs corrected target adenines efficiently and with high product purity and low indel formation in human cells.

Key findings

Engineered, via directed evolution, a DNA-acting adenosine deaminase since none exists naturally
Created adenine base editors converting A-T to G-C without double-strand breaks or a donor template
Achieved high editing efficiency, high product purity, and very low indel rates in human cells

Subjects & keywords

Biology & Genetics base editing adenine base editor crispr genome editing deaminase

Cite this paper

APA

Nicole M. Gaudelli, Alexis C. Komor, Holly A. Rees, & David R. Liu [Full author list: Nicole M. Gaudelli, Alexis C. Komor, Holly A. Rees, Michael S. Packer, Ahmed H. Badran, David I. Bryson, David R. Liu.] (2017). Programmable base editing of A•T to G•C in genomic DNA without DNA cleavage. Nature. https://doi.org/10.1038/nature24644

BibTeX

@article{gaudelli2017programmable,
  author    = {Nicole M. Gaudelli and Alexis C. Komor and Holly A. Rees and David R. Liu and {Full author list: Nicole M. Gaudelli, Alexis C. Komor, Holly A. Rees, Michael S. Packer, Ahmed H. Badran, David I. Bryson, David R. Liu.}},
  title     = {Programmable base editing of A•T to G•C in genomic DNA without DNA cleavage},
  journal   = {Nature},
  year      = {2017},
  doi       = {10.1038/nature24644},
  url       = {https://doi.org/10.1038/nature24644}
}

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