4.8 Article

Gene drive mosquitoes can aid malaria elimination by retarding Plasmodium sporogonic development

Journal

SCIENCE ADVANCES
Volume 8, Issue 38, Pages -

Publisher

AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abo1733

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Funding

  1. Bill and Melinda Gates Foundation [OPP1158151]
  2. Wellcome Trust Investigator Award [107983/Z/15/Z]
  3. Wellcome Trust [107983/Z/15/Z] Funding Source: Wellcome Trust
  4. Bill and Melinda Gates Foundation [OPP1158151] Funding Source: Bill and Melinda Gates Foundation

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Gene drives offer a promising approach for controlling malaria vectors by impeding parasite development in transgenic mosquitoes. By modifying a midgut gene in Anopheles gambiae, researchers were able to secrete antimicrobial peptides and delay oocyst development, reducing the release of infectious sporozoites. Modeling the spread of this modification revealed its potential to break the cycle of disease transmission.
Gene drives hold promise for the genetic control of malaria vectors. The development of vector population modification strategies hinges on the availability of effector mechanisms impeding parasite development in transgenic mosquitoes. We augmented a midgut gene of the malaria mosquito Anopheles gambiae to secrete two exogenous antimicrobial peptides, magainin 2 and melittin. This small genetic modification, capable of efficient nonautonomous gene drive, hampers oocyst development in both Plasmodium falciparum and Plasmodium berghei. It delays the release of infectious sporozoites, while it simultaneously reduces the life span of homozygous female transgenic mosquitoes. Modeling the spread of this modification using a large-scale agent-based model of malaria epidemiology reveals that it can break the cycle of disease transmission across a range of transmission intensities.

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