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Base editor-mediated C-to-T base conversion obviates the re-quirements of double-strand breaks,thereby showing promise as a tool for disease modeling and gene therapy (Gaudelli et al.,2017;Rees and Liu 2018).The most actively used base editor comprises a Cas9 nickase (nCas9) with cytidine deaminase and fused uracil DNA glycosylase inhibitor at the carboxy terminus of nCas9 to inhibit uracil N-glycosylase effects (Pearl,2000;Kunz et al.,2009;Rees and Liu 2018).This Cas9-mediated base editor (nCas9-BE) has been suc-cessfully used to induce C-to-T base conversion in various organ-isms,including animals and plants (Hess et al.,2017;Rees and Liu 2018).However,the editing scope of nCas9-BE is limited by its G/C-rich protospacer adjacent motif (PAM) sequences.Catalytically inactive Cpf1 from the Lachnospiraceae bacterium (dLbCpf1) was recently used to substitute nCas9 to fuse with rat cytosine deaminase APOBEC1,thereby developing a new base editor,named dCpf1-BE(Li et al.,2018).Similar to nCas9-BEs,dCpf1-BE induces C-to-T con-version within the editing scope.Several unique features inherited from LbCpf1 distinguish dCpf1-BE from nCas9-BEs,dCpf1-BE can recognize T-rich PAM on the 5'side of the protospacer and a1lows base editing in A/T-rich regions (Zetsche et al.,2015),thereby expanding the target scope for base conversion.Moreover,dCpf1-BE uses catalytically dead LbCpf1 to bind to the genome,creating extremely low levels of indels.However,dCpf1-BE showed relatively low editing efficiency at many targets in the human genome (Li et al.,2018),indicating that its practical applications are limited.The reason for this low activity is unknown.Recent studies revealed that nucleo-somes impede the access of the CRISPR (Clustered regularly inter-spaced short palindromic repeats) effector to the target DNA(Tsompana and Buck,2014;Horlbeck et al.,2016;Yarrington et al.,2018).The binding of an orthogonal and catalytically dead Cas9(dCas9) at a proximal location of target sites could alter the local chromatin structures and make inaccessible target sites available to CRISPR effectors,thereby improving gene editing efficiency(Chen et al.,2017;Liu et al.,2019a).