Hostname: page-component-cd9895bd7-lnqnp Total loading time: 0 Render date: 2024-12-31T22:53:44.389Z Has data issue: false hasContentIssue false
  • English
  • Français

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

Published online by Cambridge University Press:  04 January 2007

P. GELDHOF ,
A. VISSER ,
D. CLARK ,
G. SAUNDERS ,
C. BRITTON ,
J. GILLEARD ,
M. BERRIMAN  and
D. KNOX
P. GELDHOF*
Affiliation:
Faculty of Veterinary Medicine, Department of Virology, Parasitology and Immunology, Salisburylaan 133, B-9820 Merelbeke
A. VISSER
Affiliation:
Faculty of Veterinary Medicine, Department of Virology, Parasitology and Immunology, Salisburylaan 133, B-9820 Merelbeke
D. CLARK
Affiliation:
Moredun Research Institute, Pentlands Science Park, Bush Loan, Penicuik, EH26 0PZ, UK
G. SAUNDERS
Affiliation:
Faculty of Veterinary Medicine, Infection and Immunity, Bearsden Road, Glasgow, UK
C. BRITTON
Affiliation:
Faculty of Veterinary Medicine, Infection and Immunity, Bearsden Road, Glasgow, UK
J. GILLEARD
Affiliation:
Faculty of Veterinary Medicine, Infection and Immunity, Bearsden Road, Glasgow, UK
M. BERRIMAN
Affiliation:
Pathogen Sequencing Unit, Wellcome Trust Sanger InstituteWellcome Trust Genome Campus, Hinxton, Cambridge, UK
D. KNOX
Affiliation:
Moredun Research Institute, Pentlands Science Park, Bush Loan, Penicuik, EH26 0PZ, UK
*
*Corresponding author: Faculty of Veterinary Medicine, Department of Virology, Parasitology and Immunology, Salisburylaan 133, B-9820 Merelbeke, Belgium. E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

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.

Keywords

RNA interferenceRNAihelminthnematodetrematodegene knockdownreproducibility
Type
Review Article
Information
Parasitology , Volume 134 , Issue 5 , May 2006 , pp. 609 - 619
Copyright
Copyright © Cambridge University Press 2006

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Aboobaker, A. A. and Blaxter, M. L. (2003). Use of RNA interference to investigate gene function in the human filarial nematode parasite Brugia malayi. Molecular and Biochemical Parasitology 129, 41–51.CrossRefGoogle ScholarPubMed
Bakhetia, M., Charlton, W. L., Urwin, P. E., McPherson, M. J. and Atkinson, H. J. (2005 a). RNA interference and plant parasitic nematodes. Trends in Plant Science 10, 362–367.CrossRefGoogle ScholarPubMed
Bakhetia, M., Charlton, W., Atkinson, H. J. and McPherson, M. J. (2005 b). RNA interference of dual oxidase in the plant nematode Meloidogyne incognita. Molecular Plant-Microbe Interactions 18, 1099–1106.CrossRefGoogle ScholarPubMed
Bartel, D. P. (2004). MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116, 281–297.CrossRefGoogle ScholarPubMed
Boyle, J. P., Wu, X. J., Shoemaker, C. B. and Yoshino, T. P. (2003). Using RNA interference to manipulate endogenous gene expression in Schistosoma mansoni sporocysts. Molecular and Biochemical Parasitology 128, 205–215.CrossRefGoogle ScholarPubMed
Britton, C. and Murray, L. (2006). Using Caenorhabditis elegans for functional analysis of genes of parasitic nematodes. International Journal for Parasitology 36, 651–659.CrossRefGoogle ScholarPubMed
Chen, Q., Rehman, S., Smant, G. and Jones, J. T. (2005). Functional analysis of pathogenicity proteins of the potato cyst nematode Globodera rostochiensis using RNAi. Molecular Plant-Microbe Interactions 18, 621–625.CrossRefGoogle ScholarPubMed
Chitwood, D. J. (2003). Research on plant-parasitic nematode biology conducted by the United States Department of Agriculture-Agricultural Research Service. Pest Management Science 59, 748–753.CrossRefGoogle ScholarPubMed
Correnti, J. M. and Pearce, E. J. (2004). Transgene expression in Schistosoma mansoni: introduction of RNA into schistosomula by electroporation. Molecular and Biochemical Parasitology 137, 75–79.CrossRefGoogle ScholarPubMed
Correnti, J. M., Brindley, P. J. and Pearce, E. J. (2005). Long-term suppression of cathepsin B levels by RNA interference retards schistosome growth. Molecular and Biochemical Parasitology 143, 209–215.CrossRefGoogle ScholarPubMed
Dinguirard, N. and Yoshino, T. P. (2006). Potential role of a CD36-like class B scavenger receptor in the binding of modified low-density lipoprotein (acLDL) to the tegumental surface of Schistosoma mansoni sporocysts. Molecular and Biochemical Parasitology 146, 219–230.CrossRefGoogle Scholar
Djikeng, A., Shen, S., Tschudi, C. and Ullu, E. (2004). Analysis of gene function in Trypanosoma brucei using RNA interference. Methods in Molecular Biology 265, 73–83.Google ScholarPubMed
Fanelli, E., Di Vito, M., Jones, J. T. and De Giorgi, C. (2005). Analysis of chitin synthase function in a plant parasitic nematode, Meloidogyne artiellia, using RNAi. Gene 349, 87–95.CrossRefGoogle Scholar
Fire, A., Xu, S., Montgomery, M. K., Kostas, S. A., Driver, S. E. and Mello, C. C. (1998). Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature, London 408, 325–330.Google Scholar
Ford, L., Guiliano, D. B., Oksov, Y., Debnath, A. K., Liu, J., Williams, S. A., Blaxter, M. L. and Lustigman, S. (2005). Characterization of a novel filarial serine protease inhibitor, Ov-SPI-1, from Onchocerca volvulus, with potential multifunctional roles during development of the parasite. Journal of Biological Chemistry 280, 40 845–40 856.CrossRefGoogle ScholarPubMed
Geldhof, P., Murray, L., Couthier, A., Gilleard, J. S., McLauchlan, G., Knox, D. P. and Britton, C. (2006). Testing the efficacy of RNA interference in Haemonchus contortus. International Journal for Parasitology 36, 801–810.CrossRefGoogle ScholarPubMed
Ghedin, E., Wang, S., Foster, J. M. and Slatko, B. E. (2004). First sequenced genome of a parasitic nematode. Trends in Parasitology 20, 151–153.CrossRefGoogle ScholarPubMed
Grishok, A. (2005). RNAi mechanisms in Caenorhabditis elegans. FEBS Letters 579, 5932–5939.CrossRefGoogle ScholarPubMed
Hannon, G. J. (2002). RNA interference. Nature, London 418, 244–251.CrossRefGoogle Scholar
Huang, G., Allen, R., Davis, E. L., Baum, T. J. and Hussey, R. S. (2006). Engineering broad root-knot resistance in transgenic plants by RNAi silencing of a conserved and essential root-knot nematode parasitism gene. Proceedings of the National Academy of Sciences, USA 103, 14 302–14 306.CrossRefGoogle ScholarPubMed
Hussein, A. S., Kichenin, K. and Selkirk, M. E. (2002). Suppression of secreted acetylcholinesterase expression in Nippostrongylus brasiliensis by RNA interference. Molecular and Biochemical Parasitology 122, 91–94.CrossRefGoogle ScholarPubMed
Islam, M. K., Miyoshi, T., Yamada, M. and Tsuji, N. (2005). Pyrophosphatase of the roundworm Ascaris suum plays an essential role in the worm's molting and development. Infection and Immunity 73, 1995–2004.CrossRefGoogle ScholarPubMed
Issa, Z., Grant, W. N., Stasiuk, S. and Shoemaker, C. B. (2005). Development of methods for RNA interference in the sheep gastrointestinal parasite, Trichostrongylus colubriformis. International Journal for Parasitology 35, 935–940.CrossRefGoogle ScholarPubMed
Jaubert, S., Ledger, T. N., Laffaire, J. B., Abad, P. and Rosso, M. (2002). Direct identification of stylet proteins from root nematodes by a proteomic approach. Molecular and Biochemical Parasitology 121, 205–211.CrossRefGoogle ScholarPubMed
Kennerdell, J. R. and Carthew, R. W. (1998). Use of dsRNA-mediated genetic interference to demonstrate that frizzled and frizzled 2 act in the wingless pathway. Cell 95, 1017–1026.CrossRefGoogle ScholarPubMed
Kotze, A. C. and Bagnall, N. H. (2005). RNA interference in Haemonchus contortus: suppression of beta-tubulin gene expression in L3, L4 and adult worms in vitro. Molecular and Biochemical Parasitology 145, 101–110.CrossRefGoogle ScholarPubMed
Lander, E. S. and Waterman, M. S. (1988). Genomic mapping by fingerprinting random clones: a mathematical analysis. Genomics 2, 231–239.CrossRefGoogle ScholarPubMed
Lilley, C. J., Goodchild, S. A., Atkinson, H. J. and Urwin, P. E. (2005). Cloning and characterisation of a Heterodera glycines aminopeptidase cDNA. International Journal for Parasitology 35, 1577–1585.CrossRefGoogle ScholarPubMed
Lustigman, S., Zhang, J., Liu, J., Oksov, Y. and Hashmi, S. (2004). RNA interference targeting cathepsin L and Z-like cysteine proteases of Onchocerca volvulus confirmed their essential function during L3 molting. Molecular and Biochemical Parasitology 138, 165–170.CrossRefGoogle ScholarPubMed
Oelgeschlager, M., Larrain, J., Geissert, D. and De Robertis, E. M. (2000). The evolutionarily conserved BMP-binding protein Twisted gastrulation promotes BMP signaling. Nature, London 405, 757–763.CrossRefGoogle Scholar
Parrish, S. and Fire, A. (2001). Distinct roles for RDE-1 and RDE-4 during RNA interference in Caenorhabditis elegans. RNA 7, 1397–1402.Google ScholarPubMed
Pfarr, K., Heider, U. and Hoerauf, A. (2006). RNAi mediated silencing of actin expression in adult Litomosoides sigmodontis is specific, persistent and results in a phenotype. International Journal for Parasitology 36, 661–669.CrossRefGoogle ScholarPubMed
Rosso, M. N., Dubrana, M. P., Cimbolini, N., Jaubert, S. and Abad, P. (2005). Application of RNA interference to root-knot nematode genes encoding esophageal gland proteins. Molecular Plant-Microbe Interactions 18, 615–620.CrossRefGoogle ScholarPubMed
Scacheri, P. C., Rozenblatt-Rosen, O., Caplen, N. J., Wolfsberg, T. G., Umayam, L., Lee, J. C., Hughes, C. M., Shanmugam, K. S., Bhattacharjee, A., Meyerson, M. and Collins, F. S. (2004). Short interfering RNAs can induce unexpected and divergent changes in the levels of untargeted proteins in mammalian cells. Proceedings of the National Academy of Sciences, USA 101, 1892–1897.CrossRefGoogle ScholarPubMed
Shingles, J., Lilley, C. J., Atkinson, H. J. and Urwin, P. E. (2006). Meloidogyne incognita: Molecular and biochemical characterisation of a cathepsin L cysteine proteinase and the effect on parasitism following RNAi. Experimental Parasitology [Epub ahead of print].Google ScholarPubMed
Skelly, P. J., Da'dara, A. and Harn, D. A. (2003). Suppression of cathepsin B expression in Schistosoma mansoni by RNA interference. International Journal for Parasitology 33, 363–369.CrossRefGoogle ScholarPubMed
Tabara, H., Sarkissian, M., Kelly, W. G., Fleenor, J., Grishok, A., Timmons, L., Fire, A. and Mello, C. C. (1999). The rde-1 gene, RNA interference and transposon silencing in C. elegans. Cell 99, 123–132.CrossRefGoogle ScholarPubMed
Tavernarakis, N., Wang, S. L., Dorovkov, M., Ryazanov, A. and Driscoll, M. (2000). Heritable and inducible genetic interference by double-stranded RNA encoded by transgenes. Nature Genetics 24, 180–183.CrossRefGoogle ScholarPubMed
Ullu, E., Tshudi, C. and Chakraborty, T. (2004). RNA interference in protozoan parasites. Cell Microbiology 6, 509–519.CrossRefGoogle ScholarPubMed
Urwin, P. E., Lilley, C. J. and Atkinson, H. J. (2002). Ingestion of double-stranded RNA by preparasitic juvenile cyst nematodes leads to RNA interference. Molecular Plant-Microbe Interactions 15, 747–752.CrossRefGoogle ScholarPubMed
Visser, A., Geldhof, P., De Maere, V., Knox, D. P., Vercruysse, J. and Claerebout, E. (2006). Efficacy and specificity of RNA interference in larval life-stages of Ostertagia ostertagi. Parasitology 31, 1–7.Google Scholar
Yadav, B. C., Veluthambi, K. and Subramaniam, K. (2006). Host-generated double stranded RNA induces RNAi in plant-parasitic nematodes and protects the host from infection. Molecular and Biochemical Parasitology 148, 219–222.CrossRefGoogle ScholarPubMed