Large-scale RNAi screening uncovers new therapeutic targets in the human parasite Schistosoma mansoni

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.