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