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The development of RNA interference (RNAi) in gastrointestinal nematodes

Published online by Cambridge University Press:  30 March 2012

MURRAY E. SELKIRK
Affiliation:
Division of Cell and Molecular Biology, Department of Life Sciences, Imperial College London, London SW7 2AZ
STANLEY C. HUANG
Affiliation:
Division of Cell and Molecular Biology, Department of Life Sciences, Imperial College London, London SW7 2AZ
DAVID P. KNOX
Affiliation:
Moredun Research Institute, Pentlands Science Park, Bush Loan, Penicuik, Midlothian EH26 0PZ
COLLETTE BRITTON*
Affiliation:
Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, G61 1QH
*
*Corresponding author: E-mail:Collette.Britton@glasgow.ac.uk

Summary

Despite the utility of RNAi for defining gene function in Caenorhabditis elegans and early successes reported in parasitic nematodes, RNAi has proven to be stubbornly inconsistent or ineffective in the animal parasitic nematodes examined to date. Here, we summarise some of our experiences with RNAi in parasitic nematodes affecting animals and discuss the available data in the context of our own unpublished work, taking account of mode of delivery, larval activation, site of gene transcription and the presence/absence of essential RNAi pathway genes as defined by comparisons to C. elegans. We discuss future directions briefly including the evaluation of nanoparticles as a means to enhance delivery of interfering RNA to the target worm tissue.

Type
Research Article
Copyright
Copyright © Cambridge University Press 2012

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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, 4151.CrossRefGoogle ScholarPubMed
Avery, L. and Horvitz, H. R. (1990). Effects of starvation and neuroactive drugs on feeding in Caenorhabditis elegans. Journal of Experimental Zoology 253, 263270.CrossRefGoogle ScholarPubMed
Brownlee, D. J., Holden-Dye, L., Fairweather, I. and Walker, R. J. (1995). The action of serotonin and the nematode neuropeptide KSAYMRFamide on the pharyngeal muscle of the parasitic nematode, Ascaris suum. Parasitology 111, 379384.CrossRefGoogle ScholarPubMed
Chen, N., Xu, M. J., Nisbet, A. J., Huang, C. Q., Lin, R. Q., Yuan, Z. G., Song, H. Q. and Zhu, X. Q. (2011). Ascaris suum: RNAi mediated silencing of enolase gene expression in infective larvae. Experimental Parasitology 127, 142146.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, 7579.Google Scholar
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, 209215.CrossRefGoogle ScholarPubMed
Culotti, J. G., Von Ehrenstein, G., Culotti, M. R. and Russell, R. L. (1981). A second class of acetylcholinesterase-deficient mutants of the nematode Caenorhabditis elegans. Genetics 97, 281305.CrossRefGoogle ScholarPubMed
Dalzell, J. J., McVeigh, P., Warnock, N. D., Mitreva, M., Bird, D. M., Abad, P., Fleming, C. C., Day, T. A., Mousley, A., Marks, N. J. and Maule, A. G. (2011). RNAi effector diversity in nematodes. PLoS Neglected Tropical Diseases 5, (6): e1176.Google Scholar
Davis, R. E., Parra, A., LoVerde, P. T., Ribeiro, E., Glorioso, G. and Hodgson, S. (1999). Transient expression of DNA and RNA in parasitic helminths by using particle bombardment. Proceedings of the National Academy for Sciences, USA 96, 86878692.CrossRefGoogle ScholarPubMed
Feinberg, E. H. and Hunter, C. P. (2003). Transport of dsRNA into cells by the transmembrane protein SID-1. Science 301, 15451547.CrossRefGoogle ScholarPubMed
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 391, 806811.CrossRefGoogle ScholarPubMed
Fraser, A. G., Kamath, R. S., Zipperlen, P., Martinez-Campos, M., Sohrmann, M. and Ahringer, J. (2000). Functional genomic analysis of C. elegans chromosome I by systematic RNA interference. Nature 408, 325330.Google Scholar
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, 801810.CrossRefGoogle ScholarPubMed
Geldhof, P., Visser, A., Clark, D., Saunders, G., Britton, C., Gilleard, J., Berriman, M. and Knox, D. P. (2007). RNA interference in parasitic helminthes: current situation, potential pitfalls and future prospects. Parasitology 134, 609619.CrossRefGoogle ScholarPubMed
Grishok, A. (2005). RNAi mechanisms in Caenorhabditis elegans. FEBS Letters 579, 59325939.CrossRefGoogle ScholarPubMed
Habig, J. W., Aruscavage, P. J. and Bass, B. L. (2008). In C. elegans, high levels of dsRNA allow RNAi in the absence of RDE-4. PLoS One 3, e4052.CrossRefGoogle Scholar
Hieb, W. F. and Rothstein, M. (1968). Sterol requirement for reproduction of a free-living nematode. Science. 160, 778780.CrossRefGoogle ScholarPubMed
Higazi, T. B., Merriweather, A., Shu, L., Davis, R. and Unnasch, T. R. (2002). Brugia malayi: transient transfection by microinjection and particle bombardment. Experimental Parasitology 100, 95102.CrossRefGoogle ScholarPubMed
Huang, S. C. (2010). Development of RNA interference in parasitic nematodes. PhD Thesis, Imperial College London, pp. 265.Google Scholar
Huang, S. C., Chan, D. T., Smyth, D. J., Ball, G., Gounaris, K. and Selkirk, M. E. (2010). Activation of Nippostrongylus brasiliensis infective larvae is regulated by a pathway distinct from the hookworm Ancylostoma caninum. International Journal for Parasitology 40, 16191628.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, 9194.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, 935940.CrossRefGoogle ScholarPubMed
Jackstadt, P., Wilm, T. P., Zahner, H. and Hobom, G. (1999). Transformation of nematodes via ballistic DNA transfer. Molecular and Biochemical Parasitology 103, 261266.CrossRefGoogle ScholarPubMed
Johnson, N. M., Behm, C. A. and Trowell, S. C. (2005). Heritable and inducible gene knockdown in C. elegans using Wormgate and the ORFeome. Gene 359, 2634.CrossRefGoogle Scholar
Junio, A. B., Li, X., Massey, H. C. Jr., Nolan, T. J., Todd Lamitina, S., Sundaram, M. V. and Lok, J. B. (2008). Strongyloides stercoralis: cell- and tissue-specific transgene expression and co-transformation with vector constructs incorporating a common multifunctional 3′ UTR. Experimental Parasitology 118, 253265.CrossRefGoogle ScholarPubMed
Kamath, R. S., Fraser, A. G., Dong, Y., Poulin, G., Durbin, R., Gotta, M., Kanapin, A., Le Bot, N., Moreno, S., Sohrmann, M., Welchman, D. P., Zipperlen, P. and Ahringer, J. (2003). Systematic functional analysis of the Caenorhabditis elegans genome using RNAi. Nature 421, 231237.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, 10171026.CrossRefGoogle ScholarPubMed
Kotze, A. C. and Bagnall, N. H. (2006). 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.CrossRefGoogle ScholarPubMed
Kurzchalia, T. V. and Ward, S. (2003). Why do worms need cholesterol? Nature and Cell Biology 5, 684688.Google Scholar
Krautz-Peterson, G., Radwanska, M., Ndegwa, D., Shoemaker, C. B. and Skelly, P. J. (2007). Optimizing gene suppression in schistosomes using RNA interference. Molecular and Biochemical Parasitology 153, 194202.CrossRefGoogle ScholarPubMed
Lendner, M., Doligalska, M., Lucius, R. and Hartmann, S. (2008). Attempts to establish RNA interference in the parasitic nematode Heligmosomoides polygyrus. Molecular and Biochemical Parasitology 161, 2131.CrossRefGoogle ScholarPubMed
Lok, J. B. (2007). Strongyloides stercoralis: a model for translational research on parasitic nematode biology. WormBook Ed. The C. elegans Research Community, WormBook. doi: 10.1895/wormbook.1.134.1, http://www.wormbook.orgCrossRefGoogle Scholar
Maeda, I., Kohara, Y., Yamamoto, M. and Sugimoto, A. (2001). Large-scale analysis of gene function in Caenorhabditis elegans by high-throughput RNAi. Current Biology 11, 171176.CrossRefGoogle ScholarPubMed
Martin, R. E., Foster, L. A., Kester, A. S. and Donahue, M. J. (1987). Ascaris lumbricoides suum: morphological characterization of apparent cuticular pores by ionic permeability and electron microscopy. Experimental Parasitology 63, 329336.CrossRefGoogle ScholarPubMed
McGonigle, L., Mousley, A., Marks, N. J., Brennan, G. P., Dalton, J. P., Spithill, T. W., Day, T. A. and Maule, A. G. (2008). The silencing of cysteine proteases in Fasciola hepatica newly excysted juveniles using RNA interference reduces gut penetration. International Journal for Parasitology 38, 149155.CrossRefGoogle ScholarPubMed
Nakano, H., Amemiya, S., Shiokawa, K. and Taira, M. (2000). RNA interference for the organizer-specific gene Xlim-1 in Xenopus embryos. Biochemical and Biophysical Research Communications 274, 434439.CrossRefGoogle ScholarPubMed
Parrish, S. and Fire, A. (2001). Distinct roles for RDE-1 and RDE-4 during RNA interference in Caenorhabditis elegans. RNA 7, 13971402.Google ScholarPubMed
Pluskota, A., Horzowski, E., Bossinger, O. and von Mikecz, A. (2009). In Caenorhabditis elegans nanoparticle-bio-interactions become transparent: silica-nanoparticles induce reproductive senescence. PLoS One 4, e6622.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 and Plant Microbe Interactions 18, 615620.CrossRefGoogle ScholarPubMed
Saleh, M. C., van Rij, R. P., Hekele, A., Gillis, A., Foley, E., O'Farrell, P. H. and Andino, R. (2006). The endocytic pathway mediates cell entry of dsRNA to induce RNAi silencing. Nature Cell Biology 8, 793802.CrossRefGoogle ScholarPubMed
Samarasinghe, B., Knox, D. P. and Britton, C. (2011). Factors affecting susceptibility to RNA interference in Haemonchus contortus and in vivo silencing of an H11 aminopeptidase gene. International Journal for Parasitology 41, 5159.CrossRefGoogle ScholarPubMed
Selkirk, M. E., Lazari, O., Hussein, A. S. and Matthews, J. B. (2005). Nematode acetylcholinesterases are encoded by multiple genes and perform non-overlapping functions. Chemical and Biological Interactions 15, 157158, 263268.Google Scholar
Soutschek, J., Akinc, A., Bramlage, B., Charisse, K., Constien, R., Donoghue, M., Elbashir, S., Geick, A., Hadwiger, P., Harborth, J., John, M., Kesavan, V., Lavine, G., Pandey, R. K., Racie, T., Rajeev, K. G., Röhl, I., Toudjarska, I., Wang, G., Wuschko, S., Bumcrot, D., Koteliansky, V., Limmer, S., Manoharan, M. and Vornlocher, H. P. (2004). Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs. Nature 432, 173178.Google Scholar
Tabara, H., Grishok, A. and Mello, C. C. (1998). RNAi in C. elegans: soaking in the genome sequence. Science 282, 430431.CrossRefGoogle Scholar
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, 180183.Google Scholar
Tilney, L. G., Connelly, P. S., Guild, G. M., Vranich, K. A. and Artis, D. (2005). Adaptation of a nematode parasite to living within the mammalian epithelium. Journal of Experimental Zoology and Applied Comparative Experimental Biology 303, 927945.Google Scholar
Timmons, L., Court, D. L. and Fire, A. (2001). Ingestion of bacterially expressed dsRNAs can produce specific and potent genetic interference in Caenorhabditis elegans. Gene 263, 103112.CrossRefGoogle ScholarPubMed
Ullu, E., Tschudi, C. and Chakraborty, T. (2004). RNA interference in protozoan parasites. Cell Microbiology 6, 509519.Google Scholar
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 and Plant Microbe Interactions 15, 747752.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 133, 777783.CrossRefGoogle ScholarPubMed
Wilm, T., Demel, P., Koop, H. U., Schnabel, H. and Schnabel, R. (1999). Ballistic transformation of Caenorhabditis elegans. Gene 229, 3135.CrossRefGoogle ScholarPubMed
Winston, W. M., Sutherlin, M., Wright, A. J., Feinberg, E. H. and Hunter, C. P. (2007). Caenorhabditis elegans SID-2 is required for environmental RNA interference. Proceedings of the National Academy of Sciences, USA 104, 1056510570.CrossRefGoogle ScholarPubMed
Wolfrum, C., Shi, S., Jayaprakash, K. N., Jayaraman, M., Wang, G., Pandey, R. K., Rajeev, K. G., Nakayama, T., Charrise, K., Ndungo, E. M., Zimmermann, T., Koteliansky, V., Manoharan, M. and Stoffel, M. (2007). Mechanisms and optimization of in vivo delivery of lipophilic siRNAs. Nature Biotechnology 25, 11491157.Google Scholar
Zhang, X., Zhang, J. and Zhu, K. Y. (2010). Chitosan/double-stranded RNA nanoparticle-mediated RNA interference to silence chitin synthase genes through larval feeding in the African malaria mosquito (Anopheles gambiae). Insect Molecular Biology 19, 683693.CrossRefGoogle ScholarPubMed
Xu, S., Liu, C., Tzertzinis, G., Ghedin, E., Evans, C. C., Kaplan, R. and Unnasch, T. R. (2011). In vivo transfection of developmentally competent Brugia malayi infective larvae. International Journal for Parasitology 41, 355362.Google Scholar