Fig. 1

CRISPR/Cas9-HDR and ABE gene targeting strategies for correction of the LRRK2 p.G2019S mutation in iPSCs from a PD patient. a Sequences of the sgRNAs for the HDR and ABE strategies and the ssODN donor template for HDR. Two silent mutations were introduced by the donor ssODN as cutting sites for the restriction enzyme. b Whole genome sequencing analysis of select clones revealed that the c.G6055A (p.G2019S) mutation in LRRK2 was corrected to wild type and did not have indels or off-target editing in exon 41. The existence of the pre-designed silent variants as cutting sites for restriction enzymes in HDR-edited clones confirmed that the targeted region was replaced by HDR. c Sanger sequencing of exon 41 from the three isogenic iPSCs with mutations corrected by HDR. The designed silent variants confirmed that the targeted region was replaced by HDR. d Sanger sequencing of exon 41 from the isogenic iPSC clones with mutations corrected by ABE