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A confinable female-lethal population suppression system in the malaria vector, Anopheles gambiae .

Andrea L Smidler, James J Pai, Reema A Apte, Héctor M Sánchez C, Rodrigo M Corder, Eileen Jeffrey Gutiérrez, Neha Thakre, Igor Antoshechkin, John M Marshall, Omar S Akbari

Science advances · 2023-Jul-07 · PMID 37406109 · DOI 10.1126/sciadv.ade8903

Abstract

Malaria is among the world's deadliest diseases, predominantly affecting Sub-Saharan Africa and killing over half a million people annually. Controlling the principal vector, the mosquito Anopheles gambiae , as well as other anophelines, is among the most effective methods to control disease spread. Here, we develop a genetic population suppression system termed Ifegenia (inherited female elimination by genetically encoded nucleases to interrupt alleles) in this deadly vector. In this bicomponent CRISPR-based approach, we disrupt a female-essential gene, femaleless ( fle ), demonstrating complete genetic sexing via heritable daughter gynecide. Moreover, we demonstrate that Ifegenia males remain reproductively viable and can load both fle mutations and CRISPR machinery to induce fle mutations in subsequent generations, resulting in sustained population suppression. Through modeling, we demonstrate that iterative releases of nonbiting Ifegenia males can act as an effective, confinable, controllable, and safe population suppression and elimination system.

Evidence profile

Study type
modeling
Text reviewed by the copilot
Full text is available
Publication status
published
Corrections or retractions
none
Conflict statement
Not supplied in the PubMed record

Topics and methods

Sex determinationVector controlAnophelesMosquitoesCRISPR

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