Tesis

Genetic elimination of dengue vector mosquitoes
Megan R. Wise de Valdeza,1, Derric Nimmob, John Betza, Hong-Fei Gongb, Anthony A. Jamesc,2,
Luke Alpheyb,d,2, and William C. Black IVa
a
Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO 80523-1682; bOxitec Ltd., 71 Milton Park,
Abingdon, Oxfordshire, OX14 4RX, United Kingdom; cDepartment ofMicrobiology and Molecular Genetics and Department of Molecular Biology and
Biochemistry, University of California, Irvine, CA 92697-3900; and dDepartment of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS,
United Kingdom

Contributed by Anthony A. James, January 10, 2011 (sent for review September 29, 2010)

An approach based on mosquitoes carrying a conditional dominant
lethalgene (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, allowsgenetic 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 8.5–10∶1
OX3604C∶target eliminated the populations within 10–20 weeks.
These data support the further testing of this strain in contained
or confined fieldtrials to evaluate mating competitiveness and
environmental and other effects. Successful completion of the field
trials should facilitate incorporation of this approach into areawide dengue control or elimination efforts as a component of
an integrated vector management strategy.
genetic control ∣ sterile insect technique ∣ cage trial

D

engue fever is a rapidly emerging arthropod-borneviral
disease threatening one-third of the world’s population (1).
In the absence of effective drugs and vaccines, mitigation efforts
focus on controlling the primary mosquito vector, Aedes aegypti.
However, current control methods are inadequate and new methods are needed urgently (2, 3). A key challenge in the control of
Ae. aegypti is finding and treating each of the many breeding sites
ofthis mosquito, which oviposits in diverse natural and artificial
containers (4–6). Chemical control is increasingly restricted due
to potential human toxicity, mortality in nontarget organisms,
insecticide resistance, and other environmental impacts (7–9).
Release of insects carrying a dominant lethal (RIDL) is a genetic
control strategy derived from classical sterile insect technique
(SIT)that provides a new solution to the challenges facing
current control efforts (10–14).
SIT is a species-specific, environmentally friendly control
method that involves the rearing, sterilization, and release of
large numbers of disabled insects (15, 16). These sterile insects
mate with wild insects in the target population, thereby reducing
the reproductive potential of the target and, ifsufficient numbers
of sexually competitive insects can be released, achieving local
control or even elimination. Large-scale SIT programs have suppressed or eliminated a number of major agricultural pests (15).
SITapproaches for mosquito control have been tried (17–19) and
continue to be proposed (20, 21). Factors that may have limited
the success of these initial mosquito SIT programs and thatare
of continued concern in proposed SIT applications include reduced mating competitiveness and residual fertility of irradiated
males (22, 23), the need to release exclusively males (male
mosquitoes do not take blood meals) (20, 24), and reduction
of density-dependent larval mortality due to early acting lethality
(22, 25, 26). These limitations may be overcome using recombinant DNA...