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Split-gene drive system provides flexible application for safe laboratory investigation and potential field deployment

View ORCID ProfileVíctor López Del Amo, Alena L. Bishop, View ORCID ProfileHéctor M. Sánchez C., Jared B. Bennett, Xuechun Feng, John M. Marshall, View ORCID ProfileEthan Bier, View ORCID ProfileValentino M. Gantz
doi: https://doi.org/10.1101/684597
Víctor López Del Amo
1Section of Cell and Developmental Biology, University of California San Diego, La Jolla, CA 92093, USA
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Alena L. Bishop
1Section of Cell and Developmental Biology, University of California San Diego, La Jolla, CA 92093, USA
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Héctor M. Sánchez C.
2Division of Biostatistics and Epidemiology, School of Public Health, University of California, Berkeley CA 94720, USA
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Jared B. Bennett
3Biophysics Graduate Group, University of California, Berkeley CA 94720, USA
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Xuechun Feng
1Section of Cell and Developmental Biology, University of California San Diego, La Jolla, CA 92093, USA
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John M. Marshall
2Division of Biostatistics and Epidemiology, School of Public Health, University of California, Berkeley CA 94720, USA
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Ethan Bier
1Section of Cell and Developmental Biology, University of California San Diego, La Jolla, CA 92093, USA
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Valentino M. Gantz
1Section of Cell and Developmental Biology, University of California San Diego, La Jolla, CA 92093, USA
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  • For correspondence: vgantz@ucsd.edu
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ABSTRACT

CRISPR-based gene drives spread through populations bypassing the dictates of Mendelian genetics, offering a population-engineering tool for tackling vector-borne diseases, managing crop pests, and helping island conservation efforts; unfortunately, current technologies raise safety concerns for unintended gene propagation. Herein, we address this by splitting the two drive components, Cas9 and gRNAs, into separate alleles to form a novel trans-complementing split–gene-drive (tGD) and demonstrate its ability to promote super-Mendelian inheritance of the separate transgenes. This bi-component nature allows for individual transgene optimization and increases safety by restricting escape concerns to experimentation windows. We employ the tGD and a small– molecule-controlled version to investigate the biology of component inheritance and use our system to study the maternal effects on CRISPR inheritance, impaired homology on efficiency, and resistant allele formation. Lastly, mathematical modeling of tGD spread in a population shows potential advantages for improving current gene-drive technologies for field population modification.

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Posted June 27, 2019.
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Split-gene drive system provides flexible application for safe laboratory investigation and potential field deployment
Víctor López Del Amo, Alena L. Bishop, Héctor M. Sánchez C., Jared B. Bennett, Xuechun Feng, John M. Marshall, Ethan Bier, Valentino M. Gantz
bioRxiv 684597; doi: https://doi.org/10.1101/684597
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Split-gene drive system provides flexible application for safe laboratory investigation and potential field deployment
Víctor López Del Amo, Alena L. Bishop, Héctor M. Sánchez C., Jared B. Bennett, Xuechun Feng, John M. Marshall, Ethan Bier, Valentino M. Gantz
bioRxiv 684597; doi: https://doi.org/10.1101/684597

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