PKD2 and autosomal dominant polycystic kidney disease: To demonstrate the versatility of our genome editing approach, we have established multiple novel cell lines for the study of ADPKD by introducing targeted mutations into PKD1 and PKD2 (Supplementary Table 1–4): (1) deletions of PKD genes (Fig. 3a–d); (2) rescues of polycystin expression (Fig. 4a, b); (3) generation of cell lines incorporating multiple allelic features (Fig. 4c, d); and (4) introduction of epitope tags into the Pkd1 genomic locus by homologous recombination (Fig. 5a–d).