A suppression-modification gene drive for malaria control targeting the ultra-conserved RNA gene mir-184

Sebald A. N. Verkuijl, Giuseppe Corsano, Paolo Capriotti, Pei-Shi Yen, Maria Grazia Inghilterra, Prashanth Selvaraj, Astrid Hoermann, Aida Martinez-Sanchez, Chiamaka Valerie Ukegbu, Temesgen M. Kebede, Dina Vlachou, George K. Christophides and Nikolai Windbichler ()
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Sebald A. N. Verkuijl: Imperial College London
Giuseppe Corsano: Imperial College London
Paolo Capriotti: Imperial College London
Pei-Shi Yen: Imperial College London
Maria Grazia Inghilterra: Imperial College London
Prashanth Selvaraj: Bill and Melinda Gates Foundation
Astrid Hoermann: Imperial College London
Aida Martinez-Sanchez: Imperial College London
Chiamaka Valerie Ukegbu: Imperial College London
Temesgen M. Kebede: Imperial College London
Dina Vlachou: Imperial College London
George K. Christophides: Imperial College London
Nikolai Windbichler: Imperial College London

Nature Communications, 2025, vol. 16, issue 1, 1-14

Abstract: Abstract Gene drive technology presents a promising approach to controlling malaria vector populations. Suppression drives are intended to disrupt essential mosquito genes whereas modification drives aim to reduce the individual vectorial capacity of mosquitoes. Here we present a highly efficient homing gene drive in the African malaria vector Anopheles gambiae that targets the microRNA gene mir-184 and combines suppression with modification. Homozygous gene drive (miR-184D) individuals incur significant fitness costs, including high mortality following a blood meal, that curtail their propensity for malaria transmission. We attribute this to a role of miR-184 in regulating solute transport in the mosquito gut. However, females remain fully fertile, and pure-breeding miR-184D populations suitable for large-scale releases can be reared under laboratory conditions. Cage invasion experiments show that miR-184D can spread to fixation thereby reducing population fitness, while being able to propagate a separate antimalarial effector gene at the same time. Modelling indicates that the miR-184D drive integrates aspects of population suppression and population replacement strategies into a candidate strain that should be evaluated further as a tool for malaria eradication.

Date: 2025
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DOI: 10.1038/s41467-025-58954-5

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