![]() G-to-T♺ base pair changes in the genomic DNA of living cells.Together with ABEs, CBE-Ts and CABE-Ts enable the programmable installation of all transition mutations using laboratory-evolved TadA variants with improved properties relative to previously reported CBEs.Ĭytosine base editors (CBEs) are gene-editing enzymes capable of programmably introducing C Additionally, we report cytosine and adenine base editors (CABEs) catalyzing both A-to-I and C-to-U editing (CABE-Ts). G to T♺ across a sequence-diverse set of genomic loci, demonstrate robust activity in primary cells and cause no detectable elevation in genome-wide mutation.Here, we report the generation and characterization of CBEs that use engineered variants of TadA (CBE-T) that enable high on-target C While improved CBEs that decrease stochastic genome-wide off-targets have subsequently been reported, these editors can suffer from suboptimal on-target performance. Previous studies have shown that CBEs utilizing naturally occurring cytidine deaminases may cause unguided, genome-wide cytosine deamination. G-to-T♺ transition mutations and typically comprise a modified CRISPR–Cas enzyme, a naturally occurring cytidine deaminase, and an inhibitor of uracil repair.Cytosine base editors (CBEs) enable programmable genomic C
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