Novel genetic approaches for the management of the yellow fever mosquito, Aedes aegypti, have been developed in recent years and genetically engineered mosquitoes have been field-released for testing. There are two higher-level objectives to the use of genetic pest management in Ae. aegypti: population suppression, and population replacement. Population suppression approaches are aimed at reducing the population sizes of the vector so that they no longer efficiently spread arboviruses, and/or are no longer nuisance biters. In contrast, population replacement approaches have the goal of either replacing a wild vector-competent population with a refractory one, or to push alleles (such as anti-pathogen effectors) through the mosquito population in order to confer arboviral refractoriness. Population replacement approaches require a mechanism with which to drive the anti-pathogen through the population at super-Mendelian levels, which is referred to as a gene drive. One such form of gene drive is the use of a homing endonuclease (HEG) that can cut and paste into the genome along with any associated cargo such that hemizygous animals pass on the HEG/cargo as if they were homozygotes. The ease of programming of the CRISPR/Cas9 system has allowed for the development of gene drives in multiple mosquito species, however in Ae. aegypti the system still requires further fine tuning for the purposes of population replacement. Factors including the selection of the regulatory elements that control gene expression, HEG target site selection, and genomic insertion locus, all contribute to both the success and limitations of CRISPR/Cas9-based gene drives in Ae. aegypti. Taken together, these factors represent several of the hurdles that must be cleared in order to achieve a highly-efficient gene drive system in Ae. aegypti.

Gene drive and anti-viral effectors in the yellow fever mosquito Aedes aegypti

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