Skip to main content
×
Home
    • Aa
    • Aa

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

  • P. GELDHOF (a1), A. VISSER (a1), D. CLARK (a2), G. SAUNDERS (a3), C. BRITTON (a3), J. GILLEARD (a3), M. BERRIMAN (a4) and D. KNOX (a2)...
Abstract
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.

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

This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

A. A. Aboobaker and M. L. Blaxter (2003). Use of RNA interference to investigate gene function in the human filarial nematode parasite Brugia malayi. Molecular and Biochemical Parasitology 129, 4151.

M. Bakhetia , W. L. Charlton , P. E. Urwin , M. J. McPherson and H. J. Atkinson (2005 a). RNA interference and plant parasitic nematodes. Trends in Plant Science 10, 362367.

M. Bakhetia , W. Charlton , H. J. Atkinson and M. J. McPherson (2005 b). RNA interference of dual oxidase in the plant nematode Meloidogyne incognita. Molecular Plant-Microbe Interactions 18, 10991106.

D. P. Bartel (2004). MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116, 281297.

J. P. Boyle , X. J. Wu , C. B. Shoemaker and T. P. Yoshino (2003). Using RNA interference to manipulate endogenous gene expression in Schistosoma mansoni sporocysts. Molecular and Biochemical Parasitology 128, 205215.

C. Britton and L. Murray (2006). Using Caenorhabditis elegans for functional analysis of genes of parasitic nematodes. International Journal for Parasitology 36, 651659.

Q. Chen , S. Rehman , G. Smant and J. T. Jones (2005). Functional analysis of pathogenicity proteins of the potato cyst nematode Globodera rostochiensis using RNAi. Molecular Plant-Microbe Interactions 18, 621625.

D. J. Chitwood (2003). Research on plant-parasitic nematode biology conducted by the United States Department of Agriculture-Agricultural Research Service. Pest Management Science 59, 748753.

J. M. Correnti and E. J. Pearce (2004). Transgene expression in Schistosoma mansoni: introduction of RNA into schistosomula by electroporation. Molecular and Biochemical Parasitology 137, 7579.

J. M. Correnti , P. J. Brindley and E. J. Pearce (2005). Long-term suppression of cathepsin B levels by RNA interference retards schistosome growth. Molecular and Biochemical Parasitology 143, 209215.

N. Dinguirard and T. P. Yoshino (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, 219230.

E. Fanelli , M. Di Vito , J. T. Jones and C. De Giorgi (2005). Analysis of chitin synthase function in a plant parasitic nematode, Meloidogyne artiellia, using RNAi. Gene 349, 8795.

L. Ford , D. B. Guiliano , Y. Oksov , A. K. Debnath , J. Liu , S. A. Williams , M. L. Blaxter and S. Lustigman (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 84540 856.

P. Geldhof , L. Murray , A. Couthier , J. S. Gilleard , G. McLauchlan , D. P. Knox and C. Britton (2006). Testing the efficacy of RNA interference in Haemonchus contortus. International Journal for Parasitology 36, 801810.

E. Ghedin , S. Wang , J. M. Foster and B. E. Slatko (2004). First sequenced genome of a parasitic nematode. Trends in Parasitology 20, 151153.

A. Grishok (2005). RNAi mechanisms in Caenorhabditis elegans. FEBS Letters 579, 59325939.

G. J. Hannon (2002). RNA interference. Nature, London 418, 244251.

G. Huang , R. Allen , E. L. Davis , T. J. Baum and R. S. Hussey (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 30214 306.

A. S. Hussein , K. Kichenin and M. E. Selkirk (2002). Suppression of secreted acetylcholinesterase expression in Nippostrongylus brasiliensis by RNA interference. Molecular and Biochemical Parasitology 122, 9194.

M. K. Islam , T. Miyoshi , M. Yamada and N. Tsuji (2005). Pyrophosphatase of the roundworm Ascaris suum plays an essential role in the worm's molting and development. Infection and Immunity 73, 19952004.

Z. Issa , W. N. Grant , S. Stasiuk and C. B. Shoemaker (2005). Development of methods for RNA interference in the sheep gastrointestinal parasite, Trichostrongylus colubriformis. International Journal for Parasitology 35, 935940.

S. Jaubert , T. N. Ledger , J. B. Laffaire , P. Abad and M. Rosso (2002). Direct identification of stylet proteins from root nematodes by a proteomic approach. Molecular and Biochemical Parasitology 121, 205211.

J. R. Kennerdell and R. W. Carthew (1998). Use of dsRNA-mediated genetic interference to demonstrate that frizzled and frizzled 2 act in the wingless pathway. Cell 95, 10171026.

A. C. Kotze and N. H. Bagnall (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, 101110.

E. S. Lander and M. S. Waterman (1988). Genomic mapping by fingerprinting random clones: a mathematical analysis. Genomics 2, 231239.

C. J. Lilley , S. A. Goodchild , H. J. Atkinson and P. E. Urwin (2005). Cloning and characterisation of a Heterodera glycines aminopeptidase cDNA. International Journal for Parasitology 35, 15771585.

S. Lustigman , J. Zhang , J. Liu , Y. Oksov and S. Hashmi (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, 165170.

K. Pfarr , U. Heider and A. Hoerauf (2006). RNAi mediated silencing of actin expression in adult Litomosoides sigmodontis is specific, persistent and results in a phenotype. International Journal for Parasitology 36, 661669.

M. N. Rosso , M. P. Dubrana , N. Cimbolini , S. Jaubert and P. Abad (2005). Application of RNA interference to root-knot nematode genes encoding esophageal gland proteins. Molecular Plant-Microbe Interactions 18, 615620.

P. C. Scacheri , O. Rozenblatt-Rosen , N. J. Caplen , T. G. Wolfsberg , L. Umayam , J. C. Lee , C. M. Hughes , K. S. Shanmugam , A. Bhattacharjee , M. Meyerson and F. S. Collins (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, 18921897.

P. J. Skelly , A. Da'dara and D. A. Harn (2003). Suppression of cathepsin B expression in Schistosoma mansoni by RNA interference. International Journal for Parasitology 33, 363369.

H. Tabara , M. Sarkissian , W. G. Kelly , J. Fleenor , A. Grishok , L. Timmons , A. Fire and C. C. Mello (1999). The rde-1 gene, RNA interference and transposon silencing in C. elegans. Cell 99, 123132.

N. Tavernarakis , S. L. Wang , M. Dorovkov , A. Ryazanov and M. Driscoll (2000). Heritable and inducible genetic interference by double-stranded RNA encoded by transgenes. Nature Genetics 24, 180183.

E. Ullu , C. Tshudi and T. Chakraborty (2004). RNA interference in protozoan parasites. Cell Microbiology 6, 509519.

P. E. Urwin , C. J. Lilley and H. J. Atkinson (2002). Ingestion of double-stranded RNA by preparasitic juvenile cyst nematodes leads to RNA interference. Molecular Plant-Microbe Interactions 15, 747752.

B. C. Yadav , K. Veluthambi and K. Subramaniam (2006). Host-generated double stranded RNA induces RNAi in plant-parasitic nematodes and protects the host from infection. Molecular and Biochemical Parasitology 148, 219222.

Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Parasitology
  • ISSN: 0031-1820
  • EISSN: 1469-8161
  • URL: /core/journals/parasitology
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×

Keywords: