Abstract
Dengue is the most medically important arthropod-borne viral disease, with 50–100 million cases reported annually worldwide1. As no licensed vaccine or dedicated therapy exists for dengue, the most promising strategies to control the disease involve targeting the predominant mosquito vector, Aedes aegypti. However, the current methods to do this are inadequate. Various approaches involving genetically engineered mosquitoes have been proposed2,3,4, including the release of transgenic sterile males5,6,7,8,9,10. However, the ability of laboratory-reared, engineered male mosquitoes to effectively compete with wild males in terms of finding and mating with wild females, which is critical to the success of these strategies, has remained untested. We report data from the first open-field trial involving a strain of engineered mosquito. We demonstrated that genetically modified male mosquitoes, released across 10 hectares for a 4-week period, mated successfully with wild females and fertilized their eggs. These findings suggest the feasibility of this technology to control dengue by suppressing field populations of A. aegypti.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
WHO-TDR. Scientific Working Group Report on Dengue 162 (World Health Organization, Geneva, 2006).
Alphey, L. et al. Malaria control with genetically modified vectors. Science 298, 119–121 (2002).
Sinkins, S.P. & Gould, F. Gene drive systems for insect disease vectors. Nat. Rev. Genet. 7, 427–435 (2006).
Alphey, L. Natural and engineered mosquito immunity. J. Biol. 8, 40 (2009).
Alphey, L. et al. Sterile-insect methods for control of mosquito-borne diseases–an analysis. Vector Borne Zoonotic Dis. 10, 295–311 (2009).
Fu, G. et al. Female-specific flightless phenotype for mosquito control. Proc. Natl. Acad. Sci. USA 107, 4550–4554 (2010).
Phuc, H.K. et al. Late-acting dominant lethal genetic systems and mosquito control. BMC Biol. 5, 11 (2007).
Alphey, L., Nimmo, D., O'Connell, S. & Alphey, N. Insect population suppression using engineered insects. in Transgenesis and the Management of Vector-Borne Disease Vol. 627 (ed. Aksoy, S.) 93–103 (Landes Bioscience, Austin, Texas, 2008).
Atkinson, M.P. et al. Analyzing the control of mosquito-borne diseases by a dominant lethal genetic system. Proc. Natl. Acad. Sci. USA 104, 9540–9545 (2007).
Yakob, L., Alphey, L. & Bonsall, M. Aedes aegypti control: the concomitant role of competition, space and transgenic technologies. J. Appl. Ecol. 45, 1258–1265 (2008).
Dyck, V.A., Hendrichs, J. & Robinson, A.S. Sterile Insect Technique: Principles and Practice in Area-Wide Integrated Pest Management (Springer Netherlands, 2005).
Benedict, M.Q. & Robinson, A.S. The first releases of transgenic mosquitoes: an argument for the sterile insect technique. Trends Parasitol. 19, 349–355 (2003).
Helinski, M.E., Parker, A. & Knols, B.G.J. Radiation-induced sterility for pupal and adult stages of the malaria mosquito Anopheles arabiensis. Malar. J. 5, 41 (2006).
Thomas, D.D., Donnelly, C.A., Wood, R.J. & Alphey, L.S. Insect population control using a dominant, repressible, lethal genetic system. Science 287, 2474–2476 (2000).
Alphey, L. & Andreasen, M.H. Dominant lethality and insect population control. Mol. Biochem. Parasitol. 121, 173–178 (2002).
Simmons, G.S. et al. Field performance of a genetically engineered strain of pink bollworm. PLoS ONE 6, e24110 (2011).
Catteruccia, F., Godfray, H. & Crisanti, A. Impact of genetic manipulation on the fitness of Anopheles stephensi mosquitoes. Science 299, 1225–1227 (2003).
Irvin, N., Hoddle, M., O'Brochta, D., Carey, B. & Atkinson, P. Assessing fitness costs for transgenic Aedes aegypti expressing the GFP marker and transposase genes. Proc. Natl. Acad. Sci. USA 101, 891–896 (2004).
Marrelli, M.T., Li, C., Rasgon, J. & Jacobs-Lorena, M. Transgenic malaria-resistant mosquitoes have a fitness advantage when feeding on Plasmodium-infected blood. Proc. Natl. Acad. Sci. USA 104, 5580–5583 (2007).
Marrelli, M.T., Moreira, C.K., Kelly, D., Alphey, L. & Jacobs-Lorena, M. Mosquito transgenesis: what is the fitness cost? Trends Parasitol. 22, 197–202 (2006).
Lee, H., Vasan, S., Nazni, W. & Shanaz, M. Scientific Report on the Innovative Application of Aedes aegypti RIDL-Sterile Insect Technique to Combat Dengue and Chikungunya in Malaysia (Institute of Medical Research, Kuala Lumpur, Malaysia, 2008).
Lee, H.L., Joko, H., Nazni, W.A. & Vasan, S.S. Comparative life parameters of transgenic and wild strain of Aedes aegypti in the laboratory. Dengue Bull. 33, 103–114 (2009).
Nazni, W.A. et al. Susceptibility status of transgenic Aedes aegypti (L.) against insecticides. Dengue Bull. 33, 124–129 (2009).
Harris, A.F., Rajatileka, S. & Ranson, H. Pyrethroid resistance in Aedes aegypti from Grand Cayman. Am. J. Trop. Med. Hyg. 83, 277–284 (2010).
Papathanos, P.A. et al. Sex separation strategies: past experience and new approaches. Malar. J. 8, S5 (2009).
Lenhart, A.E., Walle, M., Cedillo, H. & Kroeger, A. Building a better ovitrap for detecting Aedes aegypti oviposition. Acta Trop. 96, 56–59 (2005).
Polson, K.A. et al. The use of ovitraps baited with hay infusion as a surveillance tool for Aedes aegypti mosquitoes in Cambodia. Dengue Bull. 26, 178–184 (2002).
Maciel-de-Freitas, R., Eiras, Á.E. & Lourenço-de-Oliveira, R. Field evaluation of effectiveness of the BG-Sentinel, a new trap for capturing adult Aedes aegypti (Diptera: Culicidae). Mem. Inst. Oswaldo Cruz 101, 321–325 (2006).
Mayer, D.G., Atzeni, M.G., Stuart, M.A., Anaman, K.A. & Butler, D.G. Mating competitiveness of irradiated flies for screwworm fly eradication campaigns. Prev. Vet. Med. 36, 1–9 (1998).
Vreysen, M.J.B. Monitoring sterile and wild insects in area-wide integrated pest management programmes. in Sterile Insect Technique. Principles and Practice in Area-Wide Integrated Pest Management (eds. Dyck, V.A., Hendrichs, J. & Robinson, A.S.) 325–361 (Springer, the Netherlands, 2005).
Shelly, T.E., McInnis, D.O., Rodd, C., Edu, J. & Pahio, E. Sterile insect technique and Mediterranean fruit fly (Diptera: Tephritidae): assessing the utility of aromatherapy in a hawaiian coffee field. J. Econ. Entomol. 100, 273–282 (2007).
Rendón, P., McInnis, D., Lance, D. & Stewart, J. Medfly (Diptera:Tephritidae) genetic sexing: large-scale field comparison of males-only and bisexual sterile fly releases in Guatemala. J. Econ. Entomol. 97, 1547–1553 (2004).
McKemey, A., Beech, C.J. & Vasan, S.S. Principles of field studies on Aedes mosquitoes. in Proceedings of the 2nd Intensive Workshop on Wild Type and Genetically Sterile Aedes Mosquitoes (eds. Vasan, S.S. & Lee, H.L.) (World Health Organization Collaborating Centre for Ecology, Taxonomy and Control of Vectors of Malaria, Filariasis and Dengue, Kuala Lumpur, 2008).
Anonymous. Risk analysis—OX513A Aedes aegypti mosquito for potential release on the Cayman Islands (Grand Cayman). (UK Parliament, deposited October 2009) 〈http://www.parliament.uk/deposits/depositedpapers/2011/DEP2011-0053.pdf.
Ansari, M.A., Singh, K., Brooks, G., Malhotra, P. & Vaidyanathan, V. The development of procedures and techniques for mass rearing of Aedes aegypti. Indian J. Med. Res. 65 (Suppl.), 91–99 (1977).
Focks, D.A. An improved separator for the developmental stages, sexes, and species of mosquitoes (Diptera: Culicidae). J. Med. Entomol. 17, 567–568 (1980).
Lukyanov, K.A. et al. Natural animal coloration can be determined by a nonfluorescent green fluorescent protein homolog. J. Biol. Chem. 275, 25879–25882 (2000).
Matz, M.V. et al. Fluorescent proteins from nonbioluminescent Anthozoa species. Nat. Biotechnol. 17, 969–973 (1999).
Acknowledgements
We thank Z. Ebanks, I. Black, Z. Curtis, C. Phillips, A. Miles and T. Matthews for technical and logistical assistance, G. Labbé and P. Gray for strain development, and G. Labbé and N. Morrison for manuscript review. We are grateful to the Lands & Survey Department of the Cayman Islands Government for permission to use imagery and data. A.F.H. thanks Adapco, Bayer and Central Life Sciences for supporting her PhD studentship. C.A.D. thanks the UK Medical Research Council for Centre funding.
Author information
Authors and Affiliations
Contributions
L.A., A.R.M., C.B., A.F.H., D.N. and W.D.P. conceived and supervised the project. A.F.H., D.N., N.K. and S.S. conducted the experiments. A.R.M., C.A.D. and L.A. analyzed the data and wrote the paper. All authors discussed the results and commented on the manuscript.
Corresponding author
Ethics declarations
Competing interests
D.N., A.R.M. S.S., C.B. and L.A. are employees of Oxitec Ltd. and have employment and/or equity interest in Oxitec. All other authors declare no competing financial interests. Oxitec and Oxford University hold patents and/or other intellectual property rights in areas related to the subject matter of this paper.
Supplementary information
Supplementary Text and Figures
Supplementary Figure 1 (PDF 225 kb)
Rights and permissions
About this article
Cite this article
Harris, A., Nimmo, D., McKemey, A. et al. Field performance of engineered male mosquitoes. Nat Biotechnol 29, 1034–1037 (2011). https://doi.org/10.1038/nbt.2019
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/nbt.2019
This article is cited by
-
Leucine aminopeptidase1 controls egg deposition and hatchability in male Aedes aegypti mosquitoes
Nature Communications (2024)
-
Versatile generation of precise gene edits in bovines using SEGCPN
BMC Biology (2023)
-
Enhancing the scalability of Wolbachia-based vector-borne disease management: time and temperature limits for storage and transport of Wolbachia-infected Aedes aegypti eggs for field releases
Parasites & Vectors (2023)
-
Arbovirus vectors insects: are botanical insecticides an alternative for its management?
Journal of Pest Science (2023)
-
Population replacement gene drive characteristics for malaria elimination in a range of seasonal transmission settings: a modelling study
Malaria Journal (2022)