Fig. 1

Inlaying TadA8e into the Nme2Cas9 domain can enhance on-target DNA editing in HEK293T cells. a Cartoon representations of the structure Nme1Cas9/sgRNA/DNA ternary complex structure (PDB: 6KC7), SaCas9/sgRNA/DNA ternary complex (PDB:7VW3) and alignment of Nme1Cas9/SaCas9 complex. Nme2Cas9 is 98% identical to Nme2Cas9 outside the WED and PAM-interacting domains. Deaminase domain insertion sites (Nme2Cas9 aa numbers) are shown as red spheres. b Comparison of A-to-G editing efficiency produced by Nme2ABE8e and four inlaid NmeABE8es using Sanger sequencing at 2 endogenous human genomic loci. Bars represent mean values, and error bars represent the s.d. values of three independent biological replicates, with * and **representing P < 0.05 and 0.01, respectively (two-tailed unpaired t test). c Comparison of A-to-G editing efficiency produced by Nme2ABE8e and Nme2ABE8e-797 using next-generation sequencing at 15 endogenous human genomic loci. Bars represent mean values, and error bars represent the s.d. of three independent biological replicates, with *, ** and *** representing P < 0.05, 0.01 and 0.001, respectively (two-tailed unpaired t test). d Heatmap showing the average editing efficiency of and editing windows of Nme2ABE8e and Nme2ABE8e-797 at each position across 26 sites, each of which was independently repeated three times