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RNA-guided gene drives can efficiently and reversibly bias inheritance in wild yeast

View ORCID ProfileJames E. DiCarlo, View ORCID ProfileAlejandro Chavez, View ORCID ProfileSven L. Dietz, View ORCID ProfileKevin M. Esvelt, View ORCID ProfileGeorge M. Church
doi: https://doi.org/10.1101/013896
James E. DiCarlo
1 Department of Genetics,
2 Harvard Medical School, Boston, Massachusetts, USA.
3 Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA
7 These authors contributed equally to this work.
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  • ORCID record for James E. DiCarlo
Alejandro Chavez
1 Department of Genetics,
2 Harvard Medical School, Boston, Massachusetts, USA.
4 Wyss Institute for Biologically Inspired Engineering, Boston, Massachusetts, USA.
5 Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA.
7 These authors contributed equally to this work.
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Sven L. Dietz
1 Department of Genetics,
2 Harvard Medical School, Boston, Massachusetts, USA.
4 Wyss Institute for Biologically Inspired Engineering, Boston, Massachusetts, USA.
6 Department for Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland.
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Kevin M. Esvelt
2 Harvard Medical School, Boston, Massachusetts, USA.
4 Wyss Institute for Biologically Inspired Engineering, Boston, Massachusetts, USA.
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  • For correspondence: esvelt@sculptingevolution.org gmc@harvard.edu
George M. Church
1 Department of Genetics,
2 Harvard Medical School, Boston, Massachusetts, USA.
4 Wyss Institute for Biologically Inspired Engineering, Boston, Massachusetts, USA.
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  • For correspondence: esvelt@sculptingevolution.org gmc@harvard.edu
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Abstract

Inheritance-biasing “gene drives” may be capable of spreading genomic alterations made in laboratory organisms through wild populations. We previously considered the potential for RNA-guided gene drives based on the versatile CRISPR/Cas9 genome editing system to serve as a general method of altering populations1. Here we report molecularly contained gene drive constructs in the yeast Saccharomyces cerevisiae that are typically copied at rates above 99% when mated to wild yeast. We successfully targeted both non-essential and essential genes, showed that the inheritance of an unrelated “cargo” gene could be biased by an adjacent drive, and constructed a drive capable of overwriting and reversing changes made by a previous drive. Our results demonstrate that RNA-guided gene drives are capable of efficiently biasing inheritance when mated to wild-type organisms over successive generations.

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Posted March 19, 2015.
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RNA-guided gene drives can efficiently and reversibly bias inheritance in wild yeast
James E. DiCarlo, Alejandro Chavez, Sven L. Dietz, Kevin M. Esvelt, George M. Church
bioRxiv 013896; doi: https://doi.org/10.1101/013896
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RNA-guided gene drives can efficiently and reversibly bias inheritance in wild yeast
James E. DiCarlo, Alejandro Chavez, Sven L. Dietz, Kevin M. Esvelt, George M. Church
bioRxiv 013896; doi: https://doi.org/10.1101/013896

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