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. 2011 Mar 22;108(12):4772-5.
doi: 10.1073/pnas.1019295108. Epub 2011 Mar 7.

Genetic elimination of dengue vector mosquitoes

Megan R Wise de Valdez  1 , Derric Nimmo, John Betz, Hong-Fei Gong, Anthony A James, Luke Alphey, William C Black 4th
Affiliations

Genetic elimination of dengue vector mosquitoes

Megan R Wise de Valdez et al. Proc Natl Acad Sci U S A. .

Abstract

An approach based on mosquitoes carrying a conditional dominant lethal gene (release of insects carrying a dominant lethal, RIDL) is being developed to control the transmission of dengue viruses by vector population suppression. A transgenic strain, designated OX3604C, of the major dengue vector, Aedes aegypti, was engineered to have a repressible female-specific flightless phenotype. This strain circumvents the need for radiation-induced sterilization, allows genetic sexing resulting in male-only releases, and permits the release of eggs instead of adult mosquitoes. OX3604C males introduced weekly into large laboratory cages containing stable target mosquito populations at initial ratios of 8.5-101 OX3604Ctarget eliminated the populations within 10-20 weeks. These data support the further testing of this strain in contained or confined field trials to evaluate mating competitiveness and environmental and other effects. Successful completion of the field trials should facilitate incorporation of this approach into area-wide dengue control or elimination efforts as a component of an integrated vector management strategy.

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Conflict of interest statement

Conflict of interest statement: The authors declare a conflict of interest (such as defined by PNAS policy). Those authors affiliated to Oxitec Ltd. (D.N., H.-F.G., and L.A.) are employees of this company, which therefore provided salary and other support for the research program. Also, such employees have shares or share options in Oxitec Ltd. Both Oxitec Ltd. and Oxford University have one or more patents or patent applications related to the subject of this paper. M.R.W.d.V., J.B., A.A.J., and W.C.B. have no patent interests, shares, or share options in Oxitec or any other entity for this technology.

Figures

Fig. 1.
Fig. 1.
Egg production in treatment and control cages. Weekly egg production is shown for each control and treatment cage. Production numbers were stable in all cages by Week 4 after population establishment. After OX3604C male release was initiated (vertical dashed line) in the treatment cages (Week 13; Week 0 PR, top time axis), egg production in the control cages continued to be stable but gradually declined in the treatment cages, with a clear reduction relative to controls by Week 5 PR. The populations in the treatment cages became extinct (defined as two consecutive weeks with no egg production) by weeks 10, 15, and 20 PR (arrows).
Fig. 2.
Fig. 2.
Adult female populations in treatment and control cages. Adult female populations were sampled weekly with BGS-Traps for one hour (no lure). The numbers of trapped females are shown. Populations had declined in all treatment cages by eight weeks PR while the populations in the control cages continued at the prerelease levels. In all treatment cages, numbers of trapped females reached zero prior to extinction (defined as two consecutive weeks without eggs; Fig. 1 and text). The mosquitoes in the control cages were collected and counted at the end of the experiment. Six hundred eighteen adult females were recovered (222, 185, and 211 from cages 1, 2, and 3, respectively). Compared with the Week 33 BGS-Trap catch of 31, 35, and 59 females, this indicates a trapping efficiency in the weekly monitoring of approximately 20%.
Fig. 3.
Fig. 3.
Progeny genotypes in the treatment cages. Random samples of eggs from each weekly collection were hatched and the larvae screened for DsRed. Two hundred larvae were screened unless otherwise marked. The percentage of DsRed larvae reached 100% in two of the three treatment cages prior to extinction. The percentage of larvae positive for the OX3604C construct in the third cage varied over time and never reached 100%. The missing data from Cage A, Week 19, was due to the eggs collected not hatching. As expected, the frequency of the transgene in the larvae from collected eggs increased before adult female numbers or egg production decreased.
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