Triple base editor catalyzes adenine, cytidine and guanine base conversions or transversion

Current base editors act up to two base substrate and generate limited base conversions, hindering their suitability for inducing DNA sequence diversity. Here, we engineered triple base editor (A, C&G-BEs) using a fusion of adenine base editor with high A/C catalytic activity and evolved N-methylpurine DNA glycosylase. A,C&G-BEs can efficiently simultaneously catalyze three base substrates (A, C and G) and introduce up to 9 types of base conversion or transversion (A-to-G/C/T,C-to-T/G/A and G-to-C/T/A) in mammalian cells and mouse embryos.