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Converting endogenous genes of the malaria mosquito into simple non-autonomous gene drives for population replacement

Astrid Hoermann, Sofia Tapanelli, Paolo Capriotti, Ellen K. G. Masters, Tibebu Habtewold, George K. Christophides, View ORCID ProfileNikolai Windbichler
doi: https://doi.org/10.1101/2020.05.09.086157
Astrid Hoermann
1Department of Life Sciences, Imperial College London, London, United Kingdom
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Sofia Tapanelli
1Department of Life Sciences, Imperial College London, London, United Kingdom
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Paolo Capriotti
1Department of Life Sciences, Imperial College London, London, United Kingdom
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Ellen K. G. Masters
1Department of Life Sciences, Imperial College London, London, United Kingdom
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Tibebu Habtewold
1Department of Life Sciences, Imperial College London, London, United Kingdom
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George K. Christophides
1Department of Life Sciences, Imperial College London, London, United Kingdom
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Nikolai Windbichler
1Department of Life Sciences, Imperial College London, London, United Kingdom
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  • ORCID record for Nikolai Windbichler
  • For correspondence: n.windbichler@imperial.ac.uk
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Abstract

Gene drives for mosquito population replacement are promising tools for malaria control. However, there is currently no clear pathway for safely testing such tools in endemic countries. The lack of well-characterized promoters for infection-relevant tissues and regulatory hurdles are further obstacles for their design and use. Here we explore how minimal genetic modifications of endogenous mosquito genes can convert them directly into non-autonomous gene drives without disrupting their expression. We co-opted the native regulatory sequences of three midgut-specific loci of the malaria vector Anopheles gambiae to host a prototypical antimalarial molecule and guide-RNAs encoded within artificial introns, that support efficient gene drive. We assess the propensity of these modifications to interfere with the development of Plasmodium falciparum and their effect on fitness. Because of their inherent simplicity and passive mode of drive such traits could form part of an accepted testing pathway of gene drives for malaria eradication.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted May 10, 2020.
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Converting endogenous genes of the malaria mosquito into simple non-autonomous gene drives for population replacement
Astrid Hoermann, Sofia Tapanelli, Paolo Capriotti, Ellen K. G. Masters, Tibebu Habtewold, George K. Christophides, Nikolai Windbichler
bioRxiv 2020.05.09.086157; doi: https://doi.org/10.1101/2020.05.09.086157
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Converting endogenous genes of the malaria mosquito into simple non-autonomous gene drives for population replacement
Astrid Hoermann, Sofia Tapanelli, Paolo Capriotti, Ellen K. G. Masters, Tibebu Habtewold, George K. Christophides, Nikolai Windbichler
bioRxiv 2020.05.09.086157; doi: https://doi.org/10.1101/2020.05.09.086157

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