Fig. 1

CC-PE enables precise genome editing at multiple endogenous sites in HEK293T cells. a Schematic diagrams of PE2, CC-PE, and direct split PE. PE2 consists of nCas9 (H840A), M-MLV RT and a pegRNA. CC-PE is expressed from two separate vectors with coiled-coil heterodimer. b Schematics of PE2, CC-PE, and direct split PE. c-h Comparison of the efficiencies of prime edits and indel byproducts generated by unsplit PE, sPE-P3P4, sPE-N5N6, sPE-ctrl, Intein-PE, MS2-PE, and SunTag-PE at NF1 (c), EMX1 (d), ERCC2 (e), B2M (f), HBB (g), and DNMT1 (h) loci in HEK293T cells. i Precise base deletion and undesired indel efficiencies of sPE-P3P4, sPE-N5N6, sPE-ctrl, and PE2 revealed by high-throughput sequencing among 4 tested loci. j Precise base substitution and undesired indel efficiencies of sPE-P3P4, sPE-N5N6, sPE-ctrl, and PE2 among 4 tested loci. k Precise base insertion and undesired indel efficiencies of sPE-P3P4, sPE-N5N6, sPE-ctrl, and PE2 among 4 tested loci. l The heatmap generated by high-throughput sequencing shows average precise editing efficiencies of sPE-P3P4, sPE-N5N6, sPE-ctrl, and PE2 among 32 tested loci. Statistical significance in c-k was determined via unpaired t-tests (*P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001, ns indicating not significant). Error bars indicated the mean ± standard deviation of at least three independent biological replicates