As vaccination of sheep with the H11 protein gives rise to protection and/or a reduction in worm burden after challenge infection (126), the authors investigated whether gene knock-down would have an effect on

worm development within the sheep host. Sheep infected with RNAi-treated larvae showed a 57% reduction in faecal egg count and 40% reduction in worm burden compared Cobimetinib to control dsRNA-treated larvae, providing evidence that the knock-down of a protective antigen mirrors the effect of vaccination (121). Thus, RNAi can potentially be utilized to elucidate gene function in vivo during actual infection, leading to the identification of crucial genes in parasite development and survival and parasite–host interaction. In conclusion, the susceptibility of parasitic nematodes to RNAi seems to be

dependent on how the trigger is delivered, the target gene, the life stage of the specific parasite and the presence of the RNAi machinery. Therefore, large-scale analysis and screening protocols might not be easily realized in nematodes but targeting genes at dsRNA accessible sites can be utilized to elucidate gene function in vivo. Therefore, RNAi has the potential to become a useful tool for the identification of vaccine candidates and drug targets. Transgenesis and RNAi have already made a tremendous impact on helminth research. Although the transgenesis techniques available today thus far have mainly been used to over-express reporter genes such as GFP and luciferase, they have also allowed analysis of the tissue-specific expression of parasite genes. In nematodes, we now see the emergence of functional

CP-673451 in vitro studies using constructs to interfere with the corresponding endogenous genes to study signal transduction pathways. Heritable transgenesis is within our grasp, and once achieved, it will open the door to the study of the effect of transgenes on infections. It will, for example, enable the examination MG-132 mouse of the activation of host immune responses, and to understand where, when and how such responses are initiated. Likewise, the development of gene trap vectors will give us a better understanding of the sets of genes that are active in particular life cycle stages. Gene silencing using RNAi is now well established in many parasitic helminths and has for the first time allowed the direct study of parasite gene function. Nevertheless, there is still an urgent need for the development of more robust transgenic technologies for use in parasitic helminths in the post-genomic era. The wealth of information made available from genome sequencing projects will undoubtedly translate into functional genomic studies in these organisms. Such studies will not only provide a deep understanding of the molecular biology of the parasite, but could ultimately be used for the identification of proteins that could be targeted with drugs or vaccines.