Development of a high-fidelity Cas9-dependent adenine base editor (ABE) system for genome editing with high-fidelity Cas9 variants

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.1 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.