Sea nettle jellyfish venom targets proteoglycans to cause cell death and pain

Here we perform a systematic analysis of sea nettle venom / host interactions. The venom shows dose-dependent cytotoxic activity in human cells and this can be blocked by dual inhibition of apoptosis and necroptosis.

Using whole-genome CRISPR screening we identified human genes and pathways that modify venom action. The top gene cluster identified regulates proteoglycan biosynthesis. We show exogenous heparin, a drug used clinically as an anticoagulant, blocks venom cytotoxicity at a physiologically relevant dose.