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Daisy-chain gene drives for the alteration of local populations

View ORCID ProfileCharleston Noble, John Min, Jason Olejarz, Joanna Buchthal, Alejandro Chavez, View ORCID ProfileAndrea L. Smidler, Erika A. DeBenedictis, George M. Church, Martin A. Nowak, Kevin M. Esvelt
doi: https://doi.org/10.1101/057307
Charleston Noble
1Department of Genetics, Harvard Medical School
2Program for Evolutionary Dynamics, Harvard University
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  • For correspondence: esvelt@mit.edu
John Min
1Department of Genetics, Harvard Medical School
3Media Laboratory, Massachusetts Institute of Technology
4Wyss Institute for Biologically Inspired Engineering, Harvard University
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  • For correspondence: esvelt@mit.edu
Jason Olejarz
2Program for Evolutionary Dynamics, Harvard University
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Joanna Buchthal
3Media Laboratory, Massachusetts Institute of Technology
4Wyss Institute for Biologically Inspired Engineering, Harvard University
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Alejandro Chavez
1Department of Genetics, Harvard Medical School
4Wyss Institute for Biologically Inspired Engineering, Harvard University
5Department of Pathology, Massachusetts General Hospital
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Andrea L. Smidler
6Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts
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  • ORCID record for Andrea L. Smidler
Erika A. DeBenedictis
3Media Laboratory, Massachusetts Institute of Technology
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George M. Church
1Department of Genetics, Harvard Medical School
4Wyss Institute for Biologically Inspired Engineering, Harvard University
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Martin A. Nowak
2Program for Evolutionary Dynamics, Harvard University
7Department of Mathematics
8Department of Organismic and Evolutionary Biology, Harvard University, USA
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Kevin M. Esvelt
3Media Laboratory, Massachusetts Institute of Technology
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Abstract

RNA-guided gene drive elements could address many ecological problems by altering the traits of wild organisms, but the likelihood of global spread tremendously complicates ethical development and use. Here we detail a localized form of CRISPR-based gene drive composed of genetic elements arranged in a daisy-chain such that each element drives the next. “Daisy drive” systems can duplicate any effect achievable using an equivalent global drive system, but their capacity to spread is limited by the successive loss of non-driving elements from the base of the chain. Releasing daisy drive organisms constituting a small fraction of the local wild population can drive a useful genetic element to local fixation for a wide range of fitness parameters without resulting in global spread. We additionally report numerous highly active guide RNA sequences sharing minimal homology that may enable evolutionary stable daisy drive as well as global CRISPR-based gene drive. Daisy drives could simplify decision-making and promote ethical use by enabling local communities to decide whether, when, and how to alter local ecosystems.

Author’s Summary ‘Global’ gene drive systems based on CRISPR are likely to spread to every population of the target species, hampering safe and ethical use. ‘Daisy drive’ systems offer a way to alter the traits of only local populations in a temporary manner. Because they can exactly duplicate the activity of any global CRISPR-based drive at a local level, daisy drives may enable safe field trials and empower local communities to make decisions concerning their own shared environments.

For more details and an animation intended for a general audience, see the summary at Sculpting Evolution.

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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-ND 4.0 International license.
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Posted June 07, 2016.
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Daisy-chain gene drives for the alteration of local populations
Charleston Noble, John Min, Jason Olejarz, Joanna Buchthal, Alejandro Chavez, Andrea L. Smidler, Erika A. DeBenedictis, George M. Church, Martin A. Nowak, Kevin M. Esvelt
bioRxiv 057307; doi: https://doi.org/10.1101/057307
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Daisy-chain gene drives for the alteration of local populations
Charleston Noble, John Min, Jason Olejarz, Joanna Buchthal, Alejandro Chavez, Andrea L. Smidler, Erika A. DeBenedictis, George M. Church, Martin A. Nowak, Kevin M. Esvelt
bioRxiv 057307; doi: https://doi.org/10.1101/057307

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