Homing reaction can also be used to spread (‘knock-in’) a novel ‘cargo’ gene through a population. The cargo could be an effector gene that disrupts parasite transmission through the mosquito. More than 28 effector genes can interfere to some extent with malaria parasite transmission (Wang and Jacobs-Lorena 2013), including antimicrobial peptides, single-chain antibodies, immune system activators, and peptides that bind to mosquito proteins in the midgut or salivary glands. Because malaria is transmitted only by female mosquitoes, a population-wide distortion of the sex ratio towards males would have a direct impact in reducing malaria transmission. In Aedes mosquitoes, there is a naturally occurring driving Y chromosome that in some crosses leads to more than 90% male progeny. Proof-of-principle demonstration of this route to drive in A. gambiae was reported by Galizi et al. (2014), who showed that expression of an engineered variant of the PpoI nuclease from a slime mold, expressed during spermatogenesis using the B2-tubulin promoter sequences, led in some lines to males producing 95% male offspring. Other sorts of gene drive systems have been proposed for spreading an effector through pest populations, including chromosomal rearrangements that display under-dominance, and various combinations of toxins and antidotes that mimic under-dominance systems, maternal effect dominant embryonic arrest (MEDEA) systems, or variants thereof (Marshall and Akbari 2016). In a MEDEA system, the progeny of heterozygous females dies unless they inherit the MEDEA element. These sorts of drivers are ‘weaker’ than those based on homing or driving sex chromosomes (Burt et al., 2017). However, when a single mosquito species that transmit malaria parasites is eliminated there is a possibility of a successor species arising to take its place. This species will start transmitting the malaria parasites.
 
Transposons should not be used to control mosquito populations. They are linked to a genetic payload which would increase the frequency of the transposable element and genetic payload in the genome of a target organism, and eventually in the population. However, transposable elements often have transposition rates that are too low to be usable. They are unpredictable owing to lack of control over their integration sites and have proven to be difficult to mobilize after integration (Tu and Li, 2013).
 
Sex-linked meiotic drives have a low resistance allele generation rate. They can be reversed and cannot be removed with wild-type. They can suppress or eliminate populations. This can bring about unanticipated ecological ramifications. They have a moderate rate of spread and can result in the extinction of some species. They can thus be used to suppress or eliminate mosquito species that transmit the malaria parasites.
 
Supernumerary B-chromosomes have been suggested as vehicles to carry payload genes. This is because they are inherited at rates that are greater than Mendelian rates and can express transcripts. However, they are poorly understood making their engineering difficult. This makes them unfavorable for mosquito control.
 
The Killer–Rescue system uses a toxin and an antidote gene that are at separate loci. It is a hypothetical threshold-dependent gene drive system. The inverse MEDEAsystem relies on a toxin that takes effect in the zygote unless it receives a maternally delivered antidote. The Merea system functions similarly to MEDEA, but the antidote to the maternal toxin is recessive. The Semele system, conversely, uses a paternal semen-based toxin and a maternally delivered antidote. TheMedusa system induces a population crash by utilizing a pair of sex-linked toxins and antidotes. In the future, RNA-guided nucleases may contribute to the development of each of these systems in mosquito species (Raul, 2018).
 
These various genetic approaches to vector control have the potential to provide several desirable features. They act to reduce disease transmission and thus can contribute to the goals of disease elimination and eradication. They are widely applicable, able to act in diverse settings, whether hypo- or holo-endemic, urban or rural, against mosquitoes that feed indoors or outdoors, during daytime or night-time, and can control mosquito populations that are otherwise difficult to access. They provide area-wide control, and therefore protection without obvious biases relating to a person’s age, wealth, or education; they should be compatible with and complementary to other disease control measures, both current and underdevelopment; and they can be relatively easy to deliver and deploy, with little or no change required in how people behave, and as a result have the potential to be highly cost-effective. It is these key features that motivate the continued development of gene drive approaches to malaria control (Burt et al., 2017).
 
Conclusion
 
Although gene drives can be useful in malaria control there is a need to employ strategies to control the spread of genetically modified mosquitoes after release. This will help prevent unintended ecological effects and keep trust in scientists (Marshall et al., 2017). This is because experiments and deterministic models have shown that drive resistance can result from mutations that block cutting by the CRISPR nuclease. The effects of this phenomenon are not always certain. However, this is not a major impediment to the invasion of unintended populations. Genetically modified mosquitoes can, however, cross international borders, even from isolated islands. Thus, there is a need to develop ‘local’, sensitive methods of monitoring population genetics, intrinsically self-exhausting gene drive systems and strategies for countering self-propagating drive systems as well as removing all engineered genes from wild populations (Noble et al., 2018). Several other promising gene drive systems have thus far only been advanced at the theoretical level.
 
There is an unknown likelihood of unauthorized releases of self-propagating gene drive systems. This is affected by species, application, containment strategies, economic motivations, drive development stages, geography and the caution of the scientists. However, the possibility of consequently having serious negative ecological consequences given the high likelihood of spread to most populations of the target species is reduced. This is because gene drive systems are typically predicted to be transient and are not designed to alter traits of the host organism or other species. Thus, there is no need for social backlash from the unauthorized spread of self-propagating gene drives (Noble et al., 2018; Funk and Rainie, 2015). However, there is a need to develop local capacity on gene drives in areas where they are to be used. This will help improve their acceptance and uptake.
 
 
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