Lentiviral delivery of RNAs to effect robust gene silencing in parasitic nematodes

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Nematode parasites (roundworms) cause severe disease in farm animals, in particular sheep and cattle, and are responsible for significant economic losses both in the UK and worldwide. Infection is controlled by treating the animals with drugs, but the roundworms are quickly becoming resistant to all available products, a phenomenon known as multidrug resistance. There is an urgent need to design new drugs or develop other means of disease control such as vaccination to protect and intensify livestock production. This aim is hampered by the inability to genetically manipulate nematode parasites in order to define proteins essential for survival or suppression of the immune system. We have developed a new method to manipulate roundworms using viruses to deliver triggers in order to silence gene expression. In this project, we aim to investigate how this works, define the pathways involved, and optimise the system to achieve long-term stable silencing of genes throughout the parasites. We will use the two most commonly used and easily manipulated laboratory models of gastrointestinal roundworm infection. Refinement of this system will enable others in the field to easily adapt and apply it to their species of choice, and will provide a means of defining new targets for control of nematode infection.