A suppression-modification gene drive for malaria control targeting the ultra-conserved RNA gene mir-184
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 ho...
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Nature Portfolio
2025-04-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-58954-5 |
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| author | Sebald A. N. Verkuijl Giuseppe Del 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 Nikolai Windbichler |
| author_facet | Sebald A. N. Verkuijl Giuseppe Del 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 Nikolai Windbichler |
| author_sort | Sebald A. N. Verkuijl |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-2a470ff1f15a49b6bdc9143b9f4b7721 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-2a470ff1f15a49b6bdc9143b9f4b77212025-08-20T03:53:32ZengNature PortfolioNature Communications2041-17232025-04-0116111410.1038/s41467-025-58954-5A suppression-modification gene drive for malaria control targeting the ultra-conserved RNA gene mir-184Sebald A. N. Verkuijl0Giuseppe Del Corsano1Paolo Capriotti2Pei-Shi Yen3Maria Grazia Inghilterra4Prashanth Selvaraj5Astrid Hoermann6Aida Martinez-Sanchez7Chiamaka Valerie Ukegbu8Temesgen M. Kebede9Dina Vlachou10George K. Christophides11Nikolai Windbichler12Department of Life Sciences, Faculty of Natural Sciences, Imperial College LondonDepartment of Life Sciences, Faculty of Natural Sciences, Imperial College LondonDepartment of Life Sciences, Faculty of Natural Sciences, Imperial College LondonDepartment of Life Sciences, Faculty of Natural Sciences, Imperial College LondonDepartment of Life Sciences, Faculty of Natural Sciences, Imperial College LondonInstitute for Disease Modeling, Bill and Melinda Gates FoundationDepartment of Life Sciences, Faculty of Natural Sciences, Imperial College LondonSection of Cell Biology and Functional Genomics, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College LondonDepartment of Life Sciences, Faculty of Natural Sciences, Imperial College LondonDepartment of Life Sciences, Faculty of Natural Sciences, Imperial College LondonDepartment of Life Sciences, Faculty of Natural Sciences, Imperial College LondonDepartment of Life Sciences, Faculty of Natural Sciences, Imperial College LondonDepartment of Life Sciences, Faculty of Natural Sciences, Imperial College LondonAbstract 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.https://doi.org/10.1038/s41467-025-58954-5 |
| spellingShingle | Sebald A. N. Verkuijl Giuseppe Del 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 Nikolai Windbichler A suppression-modification gene drive for malaria control targeting the ultra-conserved RNA gene mir-184 Nature Communications |
| title | A suppression-modification gene drive for malaria control targeting the ultra-conserved RNA gene mir-184 |
| title_full | A suppression-modification gene drive for malaria control targeting the ultra-conserved RNA gene mir-184 |
| title_fullStr | A suppression-modification gene drive for malaria control targeting the ultra-conserved RNA gene mir-184 |
| title_full_unstemmed | A suppression-modification gene drive for malaria control targeting the ultra-conserved RNA gene mir-184 |
| title_short | A suppression-modification gene drive for malaria control targeting the ultra-conserved RNA gene mir-184 |
| title_sort | suppression modification gene drive for malaria control targeting the ultra conserved rna gene mir 184 |
| url | https://doi.org/10.1038/s41467-025-58954-5 |
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