Field Cage Studies and Progressive Evaluation of Genetically-Engineered Mosquitoes

Abstract

BackgroundA 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.Methodology/Principal FindingsOX3604C 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.Conclusions/SignificanceOur 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.

Stimulating Anopheles gambiae swarms in the laboratory: application for behavioural and fitness studies

“…Short-term mating competitiveness experiments assess an important component of fitness and conducting them in large cages provides important preliminary information on the performance of GMM [26]. Considering only large cages in this study, neither the insectary used nor swarm stimuli affected the proportion of matings by transgenic males in large cages (Figure 3, Table 3).…”

Wolbachia-Based Population Control Strategy Targeting Culex quinquefasciatus Mosquitoes Proves Efficient under Semi-Field Conditions

“…So, intermediate tests under semi-field conditions are necessary to identify potential problems before proceeding to field implementation [46]. LR[ w Pip(Is)] males exhibit mating competitiveness that is indistinguishable from field collected Cx .…”

Criteria for Identifying and Evaluating Candidate Sites for Open-Field Trials of Genetically Engineered Mosquitoes

“…Release of nonsexed fsRIDL pupae into target populations at an approximately nine fsRIDL males to one wild-type male ratio eliminated those populations in 10-20 weeks. A recent trial of the same fsRIDL strain in large field cages revealed a mating competitiveness deficiency that necessitates refinements of the approach (Facchinelli et al 2013). However, these combined data support the further evaluation of fsRIDL technology as part of overall population suppression control efforts.…”

“…The Phase II field-cage trials were conducted to evaluate influences such as exposure to a wide variety of indigenous microbial flora and fluctuations in temperature, humidity, wind, and light not found in laboratory conditions (Facchinelli et al 2011, Facchinelli et al 2013. Stakeholder assessments of risks and benefits guide the decisionmaking process that determines whether product testing occurs in contained-field trials (i.e., large cages in an outdoor setting) or in confined-field trials (sites that offer geographical, environmental, or biological confinement) (World Health Organization/Tropical Disease Research 2010).…”