2023/07/05 by Andrea L. Smidler, James J. Pai, Reema A. Apte +7 · 1 voice
Agricultural and Biological Sciences · Biochemistry, Genetics and Molecular Biology · Medicine · #CRISPR and Genetic Engineering #Insect symbiosis and bacterial influences #Malaria Research and Control
paper · pdf · doi:10.1126/sciadv.ade8903
openalex publication_date 2023/07/05 · openalex created_date 2023/07/06 · openalex updated_date 2026/06/24
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.