Gehrke, J. M. et al. Nat. Biotechnol. https://doi.org/10.1038/nbt.4199 (2018).
Wang, X. et al. Nat. Biotechnol. https://doi.org/10.1038/nbt.4198 (2018).
With their ability to introduce single-base changes without cutting both strands of the DNA base, editors are the rising stars in the CRISPR portfolio. The past two years have seen advances in on-target activity, but targeting editors to a specific base while leaving those in the vicinity unchanged is still a challenge. For a C-to-T edit, a Cas9 nickase is fused to a cytidine deaminase, most commonly rat APOBEC1, and a uracil DNA glycosylase inhibitor that prevents repair of the edited base. To narrow the specificity of the base editor to a single C within the editing window, Gehrke et al. used human APOBEC3A, which requires a TCA/G motif for editing and hardly edits Cs in other sequence contexts. Independently, Wang et al. also found that human APOBEC3A has a narrower editing window and efficiently converts Cs to Ts in regions with high DNA methylation levels.