Parasitology

Review Article

RNA interference in parasitic helminths: current situation, potential pitfalls and future prospects

P. GELDHOFa1 c1, A. VISSERa1, D. CLARKa2, G. SAUNDERSa3, C. BRITTONa3, J. GILLEARDa3, M. BERRIMANa4 and D. KNOXa2

a1 Faculty of Veterinary Medicine, Department of Virology, Parasitology and Immunology, Salisburylaan 133, B-9820 Merelbeke

a2 Moredun Research Institute, Pentlands Science Park, Bush Loan, Penicuik, EH26 0PZ, UK

a3 Faculty of Veterinary Medicine, Infection and Immunity, Bearsden Road, Glasgow, UK

a4 Pathogen Sequencing Unit, Wellcome Trust Sanger Institute Wellcome Trust Genome Campus, Hinxton, Cambridge, UK

SUMMARY

RNA interference (RNAi) has become an invaluable tool for the functional analysis of genes in a wide variety of organisms including the free-living nematode Caenorhabditis elegans. Recently, attempts have been made to apply this technology to parasitic helminths of animals and plants with variable success. Gene knockdown has been reported for Schistosoma mansoni by soaking or electroporating different life-stages in dsRNA. Similar approaches have been tested on parasitic nematodes which clearly showed that, under certain conditions, it was possible to interfere with gene expression. However, despite these successes, the current utility of this technology in parasite research is questionable. First, problems have arisen with the specificity of RNAi. Treatment of the parasites with dsRNA resulted, in many cases, in non-specific effects. Second, the current RNAi methods have a limited efficiency and effects are sometimes difficult to reproduce. This was especially the case in strongylid parasites where only a small number of genes were susceptible to RNAi-mediated gene knockdown. The future application of RNAi in parasite functional genomics will greatly depend on how we can overcome these difficulties. Optimization of the dsRNA delivery methods and in vitro culture conditions will be the major challenges.

(Received August 30 2006)

(Revised October 19 2006)

(Accepted October 25 2006)

(Online publication January 04 2007)

Correspondence:

c1 *Corresponding author: Faculty of Veterinary Medicine, Department of Virology, Parasitology and Immunology, Salisburylaan 133, B-9820 Merelbeke, Belgium. E-mail: Peter.geldhof@Ugent.be

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