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

Here we develop an adenine transversion base editor, AYBE, for A-to-C and A-to-T transversion editing in mammalian cells by fusing an adenine base editor (ABE) with hypoxanthine excision protein N-methylpurine DNA glycosylase (MPG). We also engineer AYBE variants enabling targeted editing at genomic loci with higher transversion editing activity (up to 72% for A-to-C or A-to-T editing).