K-562 cells cultured in RPMI medium with 10% FBS and 100 µg ml−1 penicillin–streptomycin. hTERT RPE-1 cells in DMEM with similar supplements. RPE-1 p53−/− from Stephen Jackson. CD34+ HSPCs for scRNA-seq in StemSpan SFEM II media. Editing experiments with CD34+ HSPCs in StemSpan SFEM II medium with growth factors. Human upper airway organoids cultured in BME droplets. FIRE reporter cell line generated by lentiviral transduction of K-562 cells. Editing reagents summarized in Supplementary Table 1. Electroporation and DNA repair inhibition detailed. Flow cytometry, gDNA extraction, amplicon sequencing, nanopore sequencing, scRNA-seq, ddPCR, Sanger sequencing, and CAST-seq methods described. Statistical analysis with GraphPad Prism 10.