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Current CRISPR gene drive systems are likely to be highly invasive in wild populations

View ORCID ProfileCharleston Noble, Ben Adlam, George M. Church, View ORCID ProfileKevin M. Esvelt, Martin A. Nowak
doi: https://doi.org/10.1101/219022
Charleston Noble
1Program for Evolutionary Dynamics, Harvard University, Cambridge, MA
2Department of Genetics, Harvard Medical School, Harvard University, Boston, MA
3Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston MA
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  • ORCID record for Charleston Noble
Ben Adlam
1Program for Evolutionary Dynamics, Harvard University, Cambridge, MA
4School of Engineering and Applied Science, Harvard University, Cambridge MA
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George M. Church
2Department of Genetics, Harvard Medical School, Harvard University, Boston, MA
3Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston MA
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Kevin M. Esvelt
5Massachusetts Institute of Technology Media Lab, Cambridge, MA
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  • For correspondence: martin_nowak@harvard.edu esvelt@mit.edu
Martin A. Nowak
1Program for Evolutionary Dynamics, Harvard University, Cambridge, MA
6Department of Mathematics, Harvard University, Cambridge, MA
7Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA
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  • For correspondence: martin_nowak@harvard.edu esvelt@mit.edu
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Abstract

Recent reports have suggested that CRISPR-based gene drives are unlikely to invade wild populations due to drive-resistant alleles that prevent cutting. Here we develop mathematical models based on existing empirical data to explicitly test this assumption. We show that although resistance prevents drive systems from spreading to fixation in large populations, even the least effective systems reported to date are highly invasive. Releasing a small number of organisms often causes invasion of the local population, followed by invasion of additional populations connected by very low gene flow rates. Examining the effects of mitigating factors including standing variation, inbreeding, and family size revealed that none of these prevent invasion in realistic scenarios. Highly effective drive systems are predicted to be even more invasive. Contrary to the National Academies report on gene drive, our results suggest that standard drive systems should not be developed nor field-tested in regions harboring the host organism.

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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-ND 4.0 International license.
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Posted November 16, 2017.
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Current CRISPR gene drive systems are likely to be highly invasive in wild populations
Charleston Noble, Ben Adlam, George M. Church, Kevin M. Esvelt, Martin A. Nowak
bioRxiv 219022; doi: https://doi.org/10.1101/219022
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Current CRISPR gene drive systems are likely to be highly invasive in wild populations
Charleston Noble, Ben Adlam, George M. Church, Kevin M. Esvelt, Martin A. Nowak
bioRxiv 219022; doi: https://doi.org/10.1101/219022

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