A team of researchers developed adenine base editors (ABEs) that can convert A•T to G•C base pairs in genomic DNA without DNA cleavage. These ABEs are based on a tRNA adenosine deaminase that is fused to a catalytically impaired CRISPR-Cas9. Through extensive directed evolution and protein engineering, the researchers created seventh-generation ABEs (e.g., ABE7.10) that efficiently convert A•T to G•C base pairs in human cells with high product purity and low rates of indels. ABEs are more efficient and cleaner than current Cas9-based methods and can install disease-correcting or disease-suppressing mutations in human cells. Together with previous base editors, ABEs enable the direct, programmable introduction of all four transition mutations without double-stranded DNA cleavage. The spontaneous deamination of cytosine and 5-methylcytosine leads to C•G to T•A mutations, which account for half of known human pathogenic point mutations. The ability to convert A•T to G•C base pairs at target loci in genomic DNA of unmodified cells could enable the correction of a substantial fraction of human SNPs associated with disease. Base editing is a form of genome editing that enables direct, irreversible conversion of one base pair to another at a target genomic locus without requiring double-stranded DNA breaks, homology-directed repair, or donor DNA templates. Compared with standard genome editing methods, base editing can proceed more efficiently and with far fewer undesired products such as stochastic insertions or deletions. The most commonly used base editors are third-generation designs (BE3) comprising a catalytically impaired CRISPR-Cas9 mutant, a single-strand-specific cytidine deaminase, a uracil glycosylase inhibitor, and a nickase activity. These components enable efficient and permanent C•G to T•A base pair conversion in various organisms. Fourth-generation base editors (BE4 and BE4-Gam) further improve editing efficiency and product purity. However, all reported base editors mediate C•G to T•A conversion. In this study, the researchers used protein evolution and engineering to develop a new class of adenine base editors (ABEs) that convert A•T to G•C base pairs in DNA in bacteria and human cells. Seventh-generation ABEs efficiently convert A•T to G•C at a wide range of target genomic loci in human cells with a very high degree of product purity, exceeding the typical performance characteristics of BE3. ABEs greatly expand the scope of base editing and, together with previously described base editors, enable programmable installation of all four transitions (C to T, A to G, T to C, and G to A) in genomic DNA. The researchers evolved an adenine deaminase that processes DNA by creating defective antibioticA team of researchers developed adenine base editors (ABEs) that can convert A•T to G•C base pairs in genomic DNA without DNA cleavage. These ABEs are based on a tRNA adenosine deaminase that is fused to a catalytically impaired CRISPR-Cas9. Through extensive directed evolution and protein engineering, the researchers created seventh-generation ABEs (e.g., ABE7.10) that efficiently convert A•T to G•C base pairs in human cells with high product purity and low rates of indels. ABEs are more efficient and cleaner than current Cas9-based methods and can install disease-correcting or disease-suppressing mutations in human cells. Together with previous base editors, ABEs enable the direct, programmable introduction of all four transition mutations without double-stranded DNA cleavage. The spontaneous deamination of cytosine and 5-methylcytosine leads to C•G to T•A mutations, which account for half of known human pathogenic point mutations. The ability to convert A•T to G•C base pairs at target loci in genomic DNA of unmodified cells could enable the correction of a substantial fraction of human SNPs associated with disease. Base editing is a form of genome editing that enables direct, irreversible conversion of one base pair to another at a target genomic locus without requiring double-stranded DNA breaks, homology-directed repair, or donor DNA templates. Compared with standard genome editing methods, base editing can proceed more efficiently and with far fewer undesired products such as stochastic insertions or deletions. The most commonly used base editors are third-generation designs (BE3) comprising a catalytically impaired CRISPR-Cas9 mutant, a single-strand-specific cytidine deaminase, a uracil glycosylase inhibitor, and a nickase activity. These components enable efficient and permanent C•G to T•A base pair conversion in various organisms. Fourth-generation base editors (BE4 and BE4-Gam) further improve editing efficiency and product purity. However, all reported base editors mediate C•G to T•A conversion. In this study, the researchers used protein evolution and engineering to develop a new class of adenine base editors (ABEs) that convert A•T to G•C base pairs in DNA in bacteria and human cells. Seventh-generation ABEs efficiently convert A•T to G•C at a wide range of target genomic loci in human cells with a very high degree of product purity, exceeding the typical performance characteristics of BE3. ABEs greatly expand the scope of base editing and, together with previously described base editors, enable programmable installation of all four transitions (C to T, A to G, T to C, and G to A) in genomic DNA. The researchers evolved an adenine deaminase that processes DNA by creating defective antibiotic