Schistosomes kill 250,000 people every year. Treatment of schistosomiasis relies on a single drug (praziquantel). Unfortunately, a scarcity of molecular tools has hindered the discovery of new drug targets. Here, we describe a large-scale RNA interference screen in adult Schistosoma mansoni examining the function of 2,216 genes. We discovered 250 genes with phenotypes affecting neuromuscular function, tissue integrity, stem cell maintenance, and parasite survival. Leveraging these data, we prioritize compounds with activity against the parasites and uncover a pair of protein kinases (TAO and STK25) that cooperate to maintain muscle-specific mRNA transcription. Loss of either of these kinases results in paralysis and worm death in a mammalian host. These studies will expedite therapeutic development and invigorate studies of these neglected parasites. Large-scale RNAi screening uncovers new therapeutic targets in the human parasite Schistosoma mansoni.

RNAi was performed on worms and videos were collected when a visable phenotype was observed.