Recent advances in base editing technology and its applications in disease therapy

Base editors (BEs) are transformative genome engineering tools that enable precise nucleotide substitutions without inducing double-strand breaks (DSBs) or requiring donor DNA templates. Since the first cytosine base editor (CBE) was developed in 2016, the field has advanced rapidly, with the creation of diverse BE variants that incorporate distinct deaminases and glycosylases. These engineered editors have significantly expanded the scope of genome editing by generating deaminated bases or apurinic/apyrimidinic (AP) site lesions, thereby harnessing endogenous DNA repair or replication mechanisms to produce base transitions and transversions. Among these endogenous pathways, trans-lesion synthesis (TLS) plays a particularly critical role in converting AP sites into specific base substitutions. TLS polymerases insert nucleotides opposite AP lesions, and the final editing outcome is dictated by the unique nucleotide preferences of individual TLS polymerases. This review focuses on the action mode of different base editors, highlights their interplays with the TLS, summarizes their potential therapeutic applications and discusses perspective strategies to improve precision and expand targeting scope.