CRISPR screen reveals genes with differential fitness with polyamines

Polyamine depletion using DFMO or sardomozide, inhibitors of the polyamine biosynthesis enzymes ODC1 and AMD1, respectively, exerts cytostatic effects without inducing substantial cell death. To identify genetic dependencies under varying polyamine levels, we conducted a genome-wide CRISPR-Cas9 knockout screen across conditions with differing intracellular polyamine concentrations. K562 cells were transduced with a CRISPR sgRNA library targeting ~20,000 protein-coding genes (5 sgRNAs per gene). Following 14 days of treatment with DFMO, sgRNA abundance was compared between DFMO-treated and control cells.