Programmable A-to-Y base editing by fusing adenine base editor with N-methylpurine DNA glycosylase

Base editing is a powerful technology for precise conversion of pathogenetic base changes. Here we developed adenine transversion base editor (AYBE) to fulfill the unmet demand for A-to-C and A-to-T transversion editing in mammalian cells, by fusing adenine base editor (ABE) with hypoxanthine excision protein N-methylpurine DNA glycosylase (MPG). We further engineered AYBE variants enabling targeted editing at genomic loci with robust transversion editing activity.