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Development of zygotic and germline gene drives in mice

View ORCID ProfileChandran Pfitzner, James Hughes, View ORCID ProfileMelissa White, View ORCID ProfileMichaela Scherer, Sandra Piltz, View ORCID ProfilePaul Thomas
doi: https://doi.org/10.1101/2020.06.21.162594
Chandran Pfitzner
1School of Biological Sciences, The University of Adelaide, Adelaide, South Australia, Australia, 5005
2Precision Medicine, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia, 5000
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  • ORCID record for Chandran Pfitzner
James Hughes
1School of Biological Sciences, The University of Adelaide, Adelaide, South Australia, Australia, 5005
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Melissa White
2Precision Medicine, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia, 5000
3School of Medicine, The University of Adelaide, Adelaide, South Australia, Australia, 5005
4Robinson Research Institute, The University of Adelaide, Adelaide, South Australia, Australia, 5005
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Michaela Scherer
2Precision Medicine, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia, 5000
3School of Medicine, The University of Adelaide, Adelaide, South Australia, Australia, 5005
4Robinson Research Institute, The University of Adelaide, Adelaide, South Australia, Australia, 5005
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Sandra Piltz
2Precision Medicine, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia, 5000
3School of Medicine, The University of Adelaide, Adelaide, South Australia, Australia, 5005
4Robinson Research Institute, The University of Adelaide, Adelaide, South Australia, Australia, 5005
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Paul Thomas
2Precision Medicine, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia, 5000
3School of Medicine, The University of Adelaide, Adelaide, South Australia, Australia, 5005
4Robinson Research Institute, The University of Adelaide, Adelaide, South Australia, Australia, 5005
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  • For correspondence: paul.thomas@adelaide.edu.au
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Abstract

CRISPR-based synthetic gene drives have the potential to deliver a more effective and humane method of invasive vertebrate pest control than current strategies. Relatively efficient CRISPR gene drives have been developed in insects and yeast but not in mammals. Here we investigated the efficiency of CRISPR/Cas9-based gene drives in Mus musculus by constructing “split drive” systems with Cas9 under the control of zygotic (CAG) or germline (Vasa) promoters. While both systems generated double stranded breaks at their intended target site in vivo, no homing was detectable. Our data indicate that robust and specific Cas9 expression during meiosis is a critical requirement for the generation of efficient CRISPR-based synthetic gene drives in rodents.

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-ND 4.0 International license.
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Posted June 21, 2020.
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Development of zygotic and germline gene drives in mice
Chandran Pfitzner, James Hughes, Melissa White, Michaela Scherer, Sandra Piltz, Paul Thomas
bioRxiv 2020.06.21.162594; doi: https://doi.org/10.1101/2020.06.21.162594
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Development of zygotic and germline gene drives in mice
Chandran Pfitzner, James Hughes, Melissa White, Michaela Scherer, Sandra Piltz, Paul Thomas
bioRxiv 2020.06.21.162594; doi: https://doi.org/10.1101/2020.06.21.162594

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