base editing — papers · Status Papers

BiologyNature · Oct 2017 Open access

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

Nicole M. Gaudelli, Alexis C. Komor, Holly A. Rees and David R. Liu

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.

base editing adenine base editor crispr genome editing

BiologyNature · Apr 2016 Open access

Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage

Alexis C. Komor, Yongjoo B. Kim, Michael S. Packer, John A. Zuris and David R. Liu

This paper introduced cytosine base editing (CBE), a strategy that fuses a catalytically impaired Cas9 to a cytidine deaminase to directly convert C-G base pairs to T-A in genomic DNA without inducing double-strand breaks or requiring a donor template. The authors showed that within a programmable target window the deaminase converts cytosine to uracil, which is then read as thymine, and that inhibiting base-excision repair markedly improves editing efficiency. The approach achieved precise single-base correction in human and other mammalian cells.

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