Essential function of femaleless in female gametogenesis controls gene drive spread in Anopheles gambiae
Insecticide resistance in mosquito vectors and antimalarial drug resistance in parasites threaten progress towards malaria elimination, prompting the development of alternative control strategies such as CRISPR-Cas9 gene drives. The sex determination gene femaleless (fle, AGAP013051), which is required for female development in Anopheles gambiae, is a promising target for population-suppression…
The sex determination gene femaleless (fle), crucial for female development in Anopheles gambiae mosquitoes, is a potential target for gene drives aimed at suppressing populations. However, its functions beyond sex determination are still unclear. Researchers engineered gene drives targeting fle and used germline promoters with varying temporal expression profiles.
The zpg-driven system achieved near-perfect transmission through males but resulted in complete sterility in hemizygous females due to early disruption of fle during germline development. When cas9 expression was delayed with the spo11 promoter, female fertility was partially restored, though transmission remained close to Mendelian levels.
According to population modeling, releasing zpg-drive males at 16.9% of the wild-type population could reduce female abundance by 95% within 36 generations. These findings reveal an essential reproductive role for fle beyond its established function in sex determination, limiting gene-drive spread and offering insights for designing vector-control strategies targeting genes with essential germline functions.
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