Cross-species RNAi: Selected Ascaris summ dsRNAs can sterilize Caenorhabditis elegans [abstract]

Abstract

Studies have shown that nematode infections in pigs and humans by Ascaris worms are steadily increasing, and there is a growing concern in the scientific community about drug-resistant nematodes. Cross-species RNAinterference (RNAi), a gene silencing mechanism found in many eukaryotes, has been used in attempt sterilize Ascaris with the long-term aim of developing RNAi as an anti-parasitic agent. RNAi results in the specific degradation of targeted cellular transcripts when the organism is exposed to dsRNAs corresponding to the cognate mRNA. Four Ascaris suum genes have been successfully used for cross-species RNAi with Caenorhabiditis elegans (C. elegans) used as a “tester” species. Cultured worms were injected with the gene's corresponding dsRNA and have shown that Ascaris dsRNAs can knock out gene function. This demonstrates that dsRNA from one nematode species is able to effectively commandeer the RNAi machinery of another species to knock down an essential endogenous mRNA resulting in sterility. The success with cross-species RNAi suggests that by using nematode-specific dsRNAs, it may be possible to target multiple parasitic nematodes infecting a singe host with one or more consensus dsRNAs. The Ascaris dsRNAs that sterilize C. elegans will be tested in Ascaris suum for their ability to sterilize these parasitic worms. Also, RNAs that have proved successful in sterilizing Ascaris worms will be tested in Ascaris-infected pigs to determine whether or not they work to sterilize worms in the mammalian host.