High-throughput base editing KO screening of cellular factors for enhanced GBE.

Base editor techniques have been developed as a means of pre-cisely converting bases without the need for double-stranded DNA breaks(DSBs)or editing templates.Currently,these techniques can be used for cytosine(C)to thymine(T)conversions(cytosine base editors,CBEs)(Komor et al.,2016;Nishida et al.,2016),adenine(A)to guanine(G)conversions(adenine base editors,ABEs)(Gaudelli et al.,2017),and cytosine(C)to guanine(G)conversions(glycosylase base editors,GBEs)(Zhao et al.,2021)in mammalian cells.GBE,in particular,is a promising base editing technique capable of correct-ing up to 11％of the 32,044 pathogenic single nucleotide polymor-phisms(SNPs)known to date(Gaudelli et al.,2017).Despite its potential,the performance of GBE is still not optimal,and its editing outcomes exhibit a wider variation range than those of CBEs due to the dependence on cellular DNA repair systems(Jiang et al.,2021),which implies that efficient GBE performance remains a challenge.