One of the main reasons that hinders the application of base editors in the clinic is the trade-off between editing efficiency and editing fidelity. The off-target base editing includes Cas9-independent and Cas9-dependent manners. The Cas9-independent off-target results from the intrinsic deamination activity of the deaminase domain of a base editor, which affects random RNA or DNA molecules. Meanwhile, the Cas9-dependent off-target results from the binding of Cas9 domain to DNA sequences that show strong similarity to the target sequence. Compared to Cas9-indepedentoff-targetthathasbeenextensively studied, Cas9-dependentoff-targetbaseeditinghas received much less attention. In principle, Cas9-dependent off-target base editing could be avoided by using a high-fidelity Cas9 in the base editor. Quite a few high-f idelity Cas9 variants have been reported. Among them, several have been tested as a component of a base editor in mammalian cells. However, all these studies focused on cytosine base editor (CBE) with one recent exception in which Sniper-Cas9 is used in an adenosine base editor (Sniper ABE7.10) to reduce off-target editing. Hence, it is still unclear how high-fidelity Cas9 variants could improve the performance of ABE.