Antisense Oligonucleotides Targeting Parasite Inositol 1,4,5-Trisphosphate Receptor Inhibits Mammalian Host Cell Invasion by Trypanosoma cruzi

Chagas disease is caused by an intracellular parasitic protist, Trypanosoma cruzi. As there are no highly effective drugs against this agent that also demonstrate low toxicity, there is an urgent need for development of new drugs to treat Chagas disease. We have previously demonstrated that the parasite inositol 1,4,5-trisphosphate receptor (TcIP(3)R) is crucial for invasion of the mammalian host cell by T. cruzi. Here, we report that TcIP(3)R is a short-lived protein and that its expression is significantly suppressed in trypomastigotes. Treatment of trypomastigotes, an infective stage of T. cruzi, with antisense oligonucleotides specific to TcIP(3)R deceased TcIP(3)R protein levels and impaired trypomastigote invasion of host cells. Due to the resulting instability and very low expression level of TcIP(3)R in trypomastigotes indicates that TcIP(3)R is a promising target for antisense therapy in Chagas disease.