Abstract
Gene drives are being used to enhance a DNA sequence’s likelihood of passing between generations via sexual reproduction. Gene drives can manipulate natural populations. They can be used to suppress populations by reducing the number of individuals in a population. Some of the more than 3 000 mosquito species in the world are vectors of diseases. Malaria is a typical disease whose vectors are mosquitoes. It affects mostly tropical countries. It kills many people annually many of whom are children. Interventions currently in use such as indoor residual spraying and mosquito nets are insufficient. Gene drives can be used in different ways to control mosquito populations or to eliminate mosquito species thereby reducing malaria cases and deaths. This can be through population replacement or suppression. However, before the elimination of any mosquito species for malaria control it is necessary to consider the effects of such an action. Additionally, there is a need to review the options available for the control of mosquitoes and to create awareness on the benefits and risks of such an action. This paper, therefore, looks at the role of mosquitoes in the environment, methods of controlling mosquitoes and malaria and necessary considerations when using gene drives inter alia.
 Keywords: gene-drive, malaria, mosquito control
Introduction
The current increase in genetic modification techniques and their applications require us to carefully advance science while navigating uncertainty and aligning our research with public values. There is a need to understand the science behind these new technologies to cover knowledge gaps, be ethical, and manage the risks pertaining to their applications. An example of such technologies is the ‘gene drives. These are a genetic engineering technology that propagates a particular set of genes throughout a population. Gene drives ensure biased inheritance and enhance a DNA sequence’s likelihood of passing between generations via sexual reproduction by more than the natural 50% (Noble et al., 2018). They bias the inheritance of desired traits by cutting a wild-type allele and copying the drive system in its place (Esvelt et al., 2014). Gene drives can be used to suppress populations by reducing numbers of individuals in a population thereby resulting in changes in gene frequencies within a population. Global gene drives will spread throughout all populations of a species connected by gene flow and persist (Beaghton et al., 2016).
 
The principle of gene drives is not a new phenomenon as there are cases of the mechanism occurring naturally. For example, a gene can produce multiple copies of itself in a genome, or a gene disabling other genes to increase inheritance odds. Gene drive-modified organisms hold the potential of either yielding great benefits or harmful ecological changes. For example, gene drives have the potential to offer a high-impact, cost-effective, and durable method of controlling mosquito populations (James et al., 2018). The common gene drive systems include the maternal effect dominant embryonic arrest system, homing-based drives using homing endonuclease genes, under-dominance or heterozygote inferiority drives, sex-linked meiotic drives, and heritable microorganisms. Homing for gene knock-outs is a particularly simple mechanism of achieving drive based on the activity of endonucleases. A homing-based RNA-guided drive may be removed from a population by designing a reversal drive encoding a gRNA that targets the previous generation's drive. A homing drive may be utilized to suppress a population by homing into a critical gene, the disruption of which induces recessive sterility or lethality (Marshall et al., 2017).
 
The novelty of recent gene drives resides in the use of the CRISPR technique, which not only allows gene editing with precision, speed, and economy but also has the potential of ensuring that alterations made in wild organisms will persist in nature.CRISPR-Cas9 systems can be precisely used to alter DNA regions in order to yield a gene drive (Champer et al., 2016). CRISPR gene drives make use of CRISPR’s DNA revision mechanism by copying engineered nucleotide sequences into homologous chromosomes, thereby guaranteeing the inheritance of edited genes in all offspring (Tuna et al., 2019). CRISPR based gene drives can spread genes particularly rapidly because their components can be tailored to replace alternative copies of a targeted gene. This will ensure that only desired versions of genes are passed on to offspring. Self-propagating gene drives are designed so that they can always spread as long as there are wild organisms around while self-exhausting gene drives lose their ability to spread over time. Self-propagating CRISPR based gene drives can spread if a few organisms with the gene drive elements are released into the wild (Noble et al., 2018). 
In this paper, we discuss the methods that are used in mosquito control in malaria programs and how gene drives can be used to aid them in the control of mosquito populations. We also discuss the benefits of mosquitoes and their negative impacts on the environment.
  
Role of mosquitoes in the ecosystem and to human health
There are currently more than 3000 mosquito species in the world grouped into 39 genera and 135 subgenera (Crans, 2004). Mosquitoes exist at the bottom of the food chain and have a role in the aquatic food chain necessary in maintaining a natural balance. Mosquito larvae filter feeder which feeds on unicellular algae and other tiny organic particles thus clearing the water body of debris (Waldbauer, 1998). The larvae, in turn, serve as food for the aquatic community for fish, frogs, and tadpoles. Their role on the bottom of the food chain passes the larval stage. They serve as prey for birds, bats, and spiders, salamanders, spiders, lizards, turtles, dragonflies, swallows, and bats. The mosquito eggs are robust and survive the harsh weather, hatching when the snow melts thus providing food for migratory birds especially in Arctic tundra (Lundkvist et al., 2003). Mosquitoes depend on nectar for energy and thus act as pollinators thus ensuring, mainly aquatic plants to thrive. An example is the swamp orchids such as Habenaria obtusata to which genus Aedes have specialized as pollinators
 
Mosquitoes are known to be a vector for the transmission of several diseases known as mosquito-borne viruses (moboviruses). These moboviruses include yellow fever, West Nile virus (Hubálek and Halouzka, 1999), dengue fever (Rueda, 2004), filariasis, Zika flavivirus (Kindhauser et al., 2016), Chikungunya (Weaver and Lecuit, 2015) and other arboviruses (Gubler, 2001). They also carry malaria-causing parasites such as Plasmodium vivax and P. falciparum. Malaria has ravaged the Sub-Saharan region for over 300 000 years causing about 438 000 deaths each year (Cartolovni, 2017). Despite their well-documented role in disease transmission, mosquitoes have important direct roles to humans. Mosquito saliva has been explored for medicinal properties in cardiovascular disease and was found to produce anticoagulant factors (Stark and James, 1998). There is thus the potential for the development of anticlotting drugs, such as clotting inhibitors and capillary dilators from the molecules found in the insect's saliva. (Derbie, 2019). Also, mosquito bites have been associated with the modulation of host immune response(Schneider and Higgs, 2008). However, despite their potential usefulness to human health, there is still debate about their ultimate importance. Part of the scientific world suggests an eradication of certain species of mosquito responsible for the transmission of diseases with the hope that there will be no significant negative effect on the environment.