CRISPR/Cas9 Genome Editing of the Human Topoisomerase IIα Intron-19 5′ Splice Site Circumvents Etoposide Resistance in Human Leukemia K562 Cells

Results indicate that CRISPR/Cas9 gene editing of a suboptimal E19/I19 5′ splice site in the TOP2α gene results in circumvention of acquired drug resistance to etoposide and other TOP2-targeted drugs in a clonal K562 cell line by enhancing removal of intron 19 thereby decreasing formation of a truncated TOP2α/90 isoform and increasing expression of full-length TOP2α/170 in these resistant cells.