Genome-wide CRISPR activation screen for the identification of novel ferroptosis regulators

MYCN-amplified neuroblastoma represent tumour entities that still defy currently available treatment options, but show a marked sensitivity to ferroptosis. In order to identify the molecular determinants of this hypersensitive state, we performed genome-wide CRISPR activation (CRISPRa) screens in a representative MYCN-amplified neuroblastoma cell line (SK-N-DZ) during which we induced ferroptosis via GPX4 (RSL3) and system Xc- (Erastin) inhibition. Hits identified as negative regulators of ferroptosis were validated using a focused CRISPRa guide RNA library.