Mosquitoes and Zika: time to harness genetic modification?BMJ 2016; 353 doi: https://doi.org/10.1136/bmj.i2548 (Published 09 May 2016) Cite this as: BMJ 2016;353:i2548
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In the past, a major obstacle to the establishment of genetic methods of vector-borne disease control has been the negative fitness consequences that such methods impose on vectors.
Transgenic techniques usually involve inserting a transgene into a vector with the aim of causing sterility or making them resistant to a disease . The problem with this is that inserting a transgene into an organism tends to cause deleterious mutations, compromising its fitness . Additionally, inbreeding and crowding during mass-rearing processes reduce a vector’s competitive fitness relative to that of wild individuals [3,4]. Fitness costs associated with transgenes make them unstable in the genome, and will lead to their rapid disappearance in a population .
Moreover, these fitness costs mean that genetically modified males will be outcompeted by males from the wild population . Thus, a transgene coding for, say, early death of offspring, will not spread throughout a population without some kind of mechanism to facilitate its dissemination .
A relatively new technique, known as paratransgenesis, differs from transgenic approaches because it involves genetically modifying endosymbiotic bacteria within a vector’s gut, rather than modifying the vector itself. The bacteria are engineered to secrete molecules that stop a pathogen from developing, thus making the vector resistant to the disease . This avoids the fitness costs associated with other approaches .
Furthermore, Wolbachia, a common endosymbiotic bacterium, can be harnessed in order to drive modified bacteria throughout a population . Essentially, Wolbachia infection in a population generates a reproductive fitness advantage for infected females, meaning that it can rapidly spread to fixation in a population (see Figure 1). Because Wolbachia and many endosymbiotic bacteria are maternally inherited, Wolbachia could spread modified bacteria with it . Wolachia infection could also potentially stop reinvasion of populations where a disease has been eliminated, and may even facilitate invasion to nearby areas .
Paratransgenesis has been in development for tsetse flies [11,12], assassin bugs [13,14], and sandflies [15,16], the vectors for trypanosomiasis, Chagas disease, and leishmaniasis, respectively.
The bacterial genus Asaia has been a primary target for paratransgenesis in mosquitoes. Asaia can stably colonise tissues in many mosquito hosts, including Anopheles (the major malaria vector), and Aedes mosquitoes (vectors for dengue and Zika virus). Asaia has also been modified to secrete anti-malaria molecules , and has been shown to rapidly spread throughout populations in semi-field trials .
Some mosquito species such as Aedes albopictus naturally possess Wolbachia, whilst others, such as Anopheles gambiae and Anopheles stephensi, which have microorganisms that prevent Wolbachia infection, can be provided with antibiotics that allow Wolbachia to colonise them .
Transformed bacteria could be introduced to mosquito populations by planting infected sucrose sources in mosquito habitats: females are known to consume plant nectars as part of their diet . Bacteria could also be introduced to larvae via their aquatic habitat . Both methods likely represent simple and inexpensive methods of control, and avoid the fitness costs associated with mass-rearing vectors. Furthermore, it is relatively inexpensive to mass-produce engineered bacteria, providing a further advantage for paratransgenesis over other approaches .
Whilst genetically modifying vectors means that transgenes can only be spread vertically from parent to progeny, paratransgenesis allows for horizontal spread of modified bacteria throughout a population. Bacteria can spread via mating  and co-feeding , and can cross-colonise between species . This means that paratransgenesis can bypass reproductive isolation barriers in order to control diseases that are spread by multiple vectors, such as malaria and trypanosomiasis.
Despite its many significant advantages over other approaches of vector-borne disease control, paratransgenesis has been very much limited to laboratory-based and semi-field studies. Its application in field trials will be necessary to assess its true potential. Furthermore, its application against the Zika virus has not yet been investigated. Nonetheless, as a method of vector control it should be seriously considered, particularly in the face of the growing disease risk in the developing world.
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Competing interests: No competing interests
It is very interesting to see new technologies for the prevention of infectious diseases, such as genetic modification used in mosquitoes. Zika virus is a relatively new issue and it is of vital importance to implement techniques that prevent this virus being transmitted. This disease has devastating effects on those infected and, as discussed, in some cases the effects on fetuses are not at all favorable. Although the proposed techniques have made great progress, I believe that genetic modification can be dangerous for the species, as in the distant future populations of unmodified mosquitoes would be liquidated and tests are time-consuming and very expensive. Equally it is important to take into account the determining factors for the reproduction of this type of mosquito that transmits Zika virus and the other effects of this disease in the populations of different geographical areas to prevent a high incidence of zika around the world.
Competing interests: No competing interests
NGOs and activists who are deliberately overselling benefits from naturalistic approaches, and keep sabotaging the salvatory release of genetically modified vectors, thus perpetuating annual morbidity from mosquito transmitted diseases for hundreds of millions, and resulting annual mortality for hundreds of thousands, should be retained responsible for scientific criminal fraud/offence, and punished accordingly.
Competing interests: No competing interests