Eliminating Mosquitoes with Precision Guided Sterile Males

Abstract

The mosquito Aedes aegypti is the principal vector for arboviruses including dengue/yellow fever, chikungunya, and zika, infecting hundreds of millions of people annually. Unfortunately, traditional control methodologies are insufficient, so innovative control methods are needed. To complement existing measures, here we develop a molecular genetic control system termed precision guided sterile insect technique (pgSIT) in Aedes aegypti. PgSIT uses a simple CRISPR-based approach to generate sterile males that are deployable at any life stage. Supported by mathematical models, we empirically demonstrate that released pgSIT males can compete, suppress, and eliminate mosquitoes in multigenerational population cages. This platform technology could be used in the field, and adapted to many vectors, for controlling wild populations to curtail disease in a safe, confinable, and reversible manner.

Genetically engineered insects with sex-selection and genetic incompatibility enable population suppression

“…Release of insects with dominant lethality (RIDL), has been successfully demonstrated to suppress target mosquito populations in field trials in the Caribbean islands and South America (Harris et al, 2012). Precision-guided SIT (pgSIT) utilizes expression of Cas9 nuclease to knock out female survival and male fertility genes prior to generate potential biocontrol agents (Li et al, 2021;Kandul et al, 2019).…”

California Residents’ Perceptions of Gene Drive Systems to Control Mosquito-Borne Disease

“…Prior to any gene drive field release, these commitments include fair partnership and transparency, testing of product efficacy and safety, regulatory evaluation and risk/benefit analysis, and developing monitoring and mitigation strategies. Additionally, given the concerns related to non-confinable gene drive technologies observed in this study, the Akbari lab is prioritizing research on confineable technologies for controlling populations such as self-limiting drives ( Li et al, 2020 ) and GE-SIT systems ( Li et al, 2021 ). This is an example of how this work on community and stakeholder engagement has directly informed research and development within Team California.…”

Genetic Technologies for Sustainable Management of Insect Pests and Disease Vectors

“…Moreover, inducing lethality at an early developmental phase, such as at the embryonic stage [56][57][58][59][60], further reduces rearing costs, therefore enhancing sustainability of this approach. An example is the CRISPR-based precision guided SIT (pgSIT), initially developed in the Drosophila model, which envisages simultaneous sex sorting and sterilization of males without significant reduction in fitness [61,62]. gene or a female-specific dominant lethal (fsRIDL) gene and mass reared in the presence of tetracycline, which represses the expression of the lethal genes during rearing stages.…”