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Evolutionary dynamics of CRISPR gene drives

Charleston Noble, Jason Olejarz, Kevin M. Esvelt, George M. Church, Martin A. Nowak
doi: https://doi.org/10.1101/057281
Charleston Noble
1Program for Evolutionary Dynamics, Harvard University
2Wyss Institute for Biologically Inspired Engineering
3Department of Genetics, Harvard Medical School
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Jason Olejarz
1Program for Evolutionary Dynamics, Harvard University
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Kevin M. Esvelt
4Media Laboratory, Massachusetts Institute of Technology
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George M. Church
2Wyss Institute for Biologically Inspired Engineering
3Department of Genetics, Harvard Medical School
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Martin A. Nowak
1Program for Evolutionary Dynamics, Harvard University
5Department of Mathematics, Harvard University
6Department of Organismic and Evolutionary Biology, Harvard University, Cambridge MA 02138 USA
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  • For correspondence: martin_nowak@harvard.edu
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Abstract

The alteration of wild populations has been discussed as a solution to a number of humanity’s most pressing ecological and public health concerns. Enabled by the recent revolution in genome editing, CRISPR gene drives, selfish genetic elements which can spread through populations even if they confer no advantage to their host organism, are rapidly emerging as the most promising approach. But before real-world applications are considered, it is imperative to develop a clear understanding of the outcomes of drive release in nature. Toward this aim, we mathematically study the evolutionary dynamics of CRISPR gene drives. We demonstrate that the emergence of drive-resistant alleles presents a major challenge to previously reported constructs, and we show that an alternative design which selects against resistant alleles greatly improves evolutionary stability. We discuss all results in the context of CRISPR technology and provide insights which inform the engineering of practical gene drive systems.

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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-NC-ND 4.0 International license.
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Posted June 07, 2016.
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Evolutionary dynamics of CRISPR gene drives
Charleston Noble, Jason Olejarz, Kevin M. Esvelt, George M. Church, Martin A. Nowak
bioRxiv 057281; doi: https://doi.org/10.1101/057281
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Evolutionary dynamics of CRISPR gene drives
Charleston Noble, Jason Olejarz, Kevin M. Esvelt, George M. Church, Martin A. Nowak
bioRxiv 057281; doi: https://doi.org/10.1101/057281

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