Researchers reported directed-evolution and guide-RNA engineering strategies that materially improved the precision of adenine base editors, reducing unwanted bystander edits and widening the editors’ clinical relevance. The work combined enzyme evolution with 3′-extended guide RNAs to sharpen target selectivity and was published in Nature Biotechnology on Jan. 2, 2026. The paper presents biochemical characterization, cellular assays and follow-up validations showing smaller off-target windows and higher product purity. The study directly addresses a key translational bottleneck for base-editing therapies — collateral edits at nearby adenines — and outlines a practical path for upgrading existing editor platforms. Methods included iterative library screening, in vitro activity profiling and cellular testing across clinically relevant loci. The authors highlight applications for pathogenic single-nucleotide variants where bystander edits have previously blocked clinical progress. A companion technical advance in the same issue introduced CHANGE-seq-BE, a genome-wide, high-sensitivity assay to map base-editor-induced off-target activity, enabling the community to quantify how much the new directed-evolution variants reduce off-target footprints.