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Daisy-chain gene drives for the alteration of local populations.


ABSTRACT: If they are able to spread in wild populations, CRISPR-based gene-drive elements would provide new ways to address ecological problems by altering the traits of wild organisms, but the potential for uncontrolled spread tremendously complicates ethical development and use. Here, we detail a self-exhausting form of CRISPR-based drive system comprising genetic elements arranged in a daisy chain such that each drives the next. "Daisy-drive" systems can locally duplicate any effect achievable by using an equivalent self-propagating drive system, but their capacity to spread is limited by the successive loss of nondriving elements from one end of the chain. Releasing daisy-drive organisms constituting a small fraction of the local wild population can drive a useful genetic element nearly to local fixation for a wide range of fitness parameters without self-propagating spread. We additionally report numerous highly active guide RNA sequences sharing minimal homology that may enable evolutionarily stable daisy drive as well as self-propagating CRISPR-based gene drive. Especially when combined with threshold dependence, daisy drives could simplify decision-making and promote ethical use by enabling local communities to decide whether, when, and how to alter local ecosystems.

SUBMITTER: Noble C 

PROVIDER: S-EPMC6486765 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Daisy-chain gene drives for the alteration of local populations.

Noble Charleston C   Min John J   Olejarz Jason J   Buchthal Joanna J   Chavez Alejandro A   Smidler Andrea L AL   DeBenedictis Erika A EA   Church George M GM   Church George M GM   Nowak Martin A MA   Esvelt Kevin M KM  

Proceedings of the National Academy of Sciences of the United States of America 20190402 17


If they are able to spread in wild populations, CRISPR-based gene-drive elements would provide new ways to address ecological problems by altering the traits of wild organisms, but the potential for uncontrolled spread tremendously complicates ethical development and use. Here, we detail a self-exhausting form of CRISPR-based drive system comprising genetic elements arranged in a daisy chain such that each drives the next. "Daisy-drive" systems can locally duplicate any effect achievable by usin  ...[more]

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