The article reports the development of adenine base editors (ABEs) that can convert A•T base pairs to G•C in genomic DNA without cleaving the DNA. The authors evolved a tRNA adenosine deaminase to function on DNA when fused to a catalytically impaired CRISPR-Cas9. Through extensive directed evolution and protein engineering, they developed seventh-generation ABEs (e.g., ABEM.10) that efficiently convert target A•T to G•C base pairs in human cells with high product purity and low rates of indels. ABEs introduce point mutations more efficiently and cleanly than current Cas9 nuclease-based methods and can install disease-correcting or disease-suppressing mutations in human cells. This advancement in genome editing enables the direct, programmable introduction of all four transition mutations (C•G to T•A, T•C to A•G, G•C to A•T, and C•G to G•C) without double-stranded DNA cleavage.The article reports the development of adenine base editors (ABEs) that can convert A•T base pairs to G•C in genomic DNA without cleaving the DNA. The authors evolved a tRNA adenosine deaminase to function on DNA when fused to a catalytically impaired CRISPR-Cas9. Through extensive directed evolution and protein engineering, they developed seventh-generation ABEs (e.g., ABEM.10) that efficiently convert target A•T to G•C base pairs in human cells with high product purity and low rates of indels. ABEs introduce point mutations more efficiently and cleanly than current Cas9 nuclease-based methods and can install disease-correcting or disease-suppressing mutations in human cells. This advancement in genome editing enables the direct, programmable introduction of all four transition mutations (C•G to T•A, T•C to A•G, G•C to A•T, and C•G to G•C) without double-stranded DNA cleavage.