Abstract
Mosquito-borne pathogens place an enormous burden on human health. The existing toolkit is insufficient to support ongoing vector-control efforts towards meeting disease elimination and eradication goals. The perspective that genetic approaches can potentially add a significant set of tools toward mosquito control is not new, but the recent improvements in site-specific gene editing with CRISPR/Cas9 systems have enhanced our ability to both study mosquito biology using reverse genetics and produce genetics-based tools. Cas9-mediated gene-editing is an efficient and adaptable platform for gene drive strategies, which have advantages over innundative release strategies for introgressing desirable suppression and pathogen-blocking genotypes into wild mosquito populations; until recently, an effective gene drive has been largely out of reach. Many considerations will inform the effective use of new genetic tools, including gene drives. Here we review the lengthy history of genetic advances in mosquito biology and discuss both the impact of efficient site-specific gene editing on vector biology and the resulting potential to deploy new genetic tools for the abatement of mosquito-borne disease.
Highlights
Wolbachia does drive a set of genes into mosquito populations that was previously foreign, the endosymbiont is maternally inherited and integrations of Wolbachia genes have been identified in many Wolbachia host species which is perhaps not surprising given that the bacterial genome is heavily occupied by repeats and transposable elements, [95,96,97,98,99,100,101,102]
The Cas9/single guide RNA (sgRNA) complex and homing endonuclease genes (HEGs) have both been proposed as the basis of both reversal mechanisms including designs for synthetic constructs driven in trans by another construct, even in several iterations, in order to limit the spread of independent self-driving constructs in the case of an accidental release [75,152,274,275]
The technical innovations that have led to efficient gene drives have caused a shift of focus in the field of vector biology from tool development that might allow us to use genetics to combat disease vectors, to considerations, experimentation, and modeling of what it will look like to use these approaches effectively
Summary
Vector control is critical to the reduction vector-borne diseases [1,2]. When mosquitoes were identified as vectors of the pathogens causing diseases such as malaria and yellow fever, efforts were undertaken to eliminate mosquitoes from disease-endemic regions [3,4,5,6]. In 1939 the discovery of DDT (dichloro-diphenyl-trichlorethane) as a persistent insecticide for use against mosquitoes introduced the possibility of sustainable mosquito control and a new objective emerged: global malaria eradication. Serebrovskii, while working with Muller, who realized that X-ray-induced chromosomal translocations caused sterility in offspring heterozygous for the translocation [12,13] and by Knipling who, while working for the USDA on the screwworm, Cochliomya hominvorax, observed that the agricultural pest was monogamous and males of the species were sexually aggressive [14] These observations along with Muller’s insect X-ray sterilization procedures, led to a screwworm sterilization program that was the basis of the Sterile Insect Technique (SIT), an approach to pest control that eventually led to the elimination of the screwworm from the entire continent of North America in 1968 [14,15]. Releases of each species into the other’s regions led to local elimination in both regions [16,17,18]
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