Field Cage Studies and Progressive Evaluation of Genetically-Engineered Mosquitoes
Open Access
- 17 January 2013
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLoS Neglected Tropical Diseases
- Vol. 7 (1), e2001
- https://doi.org/10.1371/journal.pntd.0002001
Abstract
A genetically-engineered strain of the dengue mosquito vector Aedes aegypti, designated OX3604C, was evaluated in large outdoor cage trials for its potential to improve dengue prevention efforts by inducing population suppression. OX3604C is engineered with a repressible genetic construct that causes a female-specific flightless phenotype. Wild-type females that mate with homozygous OX3604C males will not produce reproductive female offspring. Weekly introductions of OX3604C males eliminated all three targeted Ae. aegypti populations after 10–20 weeks in a previous laboratory cage experiment. As part of the phased, progressive evaluation of this technology, we carried out an assessment in large outdoor field enclosures in dengue endemic southern Mexico. OX3604C males were introduced weekly into field cages containing stable target populations, initially at 10∶1 ratios. Statistically significant target population decreases were detected in 4 of 5 treatment cages after 17 weeks, but none of the treatment populations were eliminated. Mating competitiveness experiments, carried out to explore the discrepancy between lab and field cage results revealed a maximum mating disadvantage of up 59.1% for OX3604C males, which accounted for a significant part of the 97% fitness cost predicted by a mathematical model to be necessary to produce the field cage results. Our results indicate that OX3604C may not be effective in large-scale releases. A strain with the same transgene that is not encumbered by a large mating disadvantage, however, could have improved prospects for dengue prevention. Insights from large outdoor cage experiments may provide an important part of the progressive, stepwise evaluation of genetically-engineered mosquitoes. The absence of a commercially-available dengue vaccine or anti-viral drug makes control of Aedes aegypti, the principal dengue mosquito vector, the only available method to prevent this disease. Sustained, effective application of vector control, however, has been difficult and this led to the call for innovative strategies, including genetic approaches. Here, the authors investigated the ability of a genetically-engineered strain of Ae. aegypti to eliminate wild mosquito populations in large outdoor cages. Females of the engineered strain cannot fly and, therefore, cannot mate or take blood meals necessary to lay viable eggs. Wild females that mate with genetically-engineered males, therefore, will not produce reproductive female offspring. In this study, although population reductions were detected in 4 of 5 field cages, none of the wild mosquito populations were eliminated. A mating disadvantage for genetically-engineered males appeared to account for a significant part of their fitness disadvantage. Results suggest that this specific strain may not be effective in a large-scale release and that new strains with the same or similar transgene, but improved mating performance, may be more effective for preventing dengue. Results also indicate that large outdoor cage experiments may provide valuable insights into the progressive, stepwise assessment of genetically-engineered mosquitoes.Keywords
This publication has 28 references indexed in Scilit:
- Development of a Semi-Field System for Contained Field Trials with Aedes aegypti in Southern MexicoThe American Journal of Tropical Medicine and Hygiene, 2011
- Comparison of Life History Characteristics of the Genetically Modified OX513A Line and a Wild Type Strain of Aedes aegyptiPLOS ONE, 2011
- Genetic elimination of dengue vector mosquitoesProceedings of the National Academy of Sciences of the United States of America, 2011
- Consequences of the Expanding Global Distribution of Aedes albopictus for Dengue Virus TransmissionPLoS Neglected Tropical Diseases, 2010
- Sterile-Insect Methods for Control of Mosquito-Borne Diseases: An AnalysisVector-Borne and Zoonotic Diseases, 2010
- Female-specific flightless phenotype for mosquito controlProceedings of the National Academy of Sciences of the United States of America, 2010
- Conceptual framework and rationaleMalaria Journal, 2009
- Skeeter Buster: A Stochastic, Spatially Explicit Modeling Tool for Studying Aedes aegypti Population Replacement and Population Suppression StrategiesPLoS Neglected Tropical Diseases, 2009
- Defining Challenges and Proposing Solutions for Control of the Virus Vector Aedes aegyptiPLoS Medicine, 2008
- Engineering RNA interference-based resistance to dengue virus type 2 in genetically modified Aedes aegyptiProceedings of the National Academy of Sciences of the United States of America, 2006