Daisy-chain gene drives for the alteration of local populations
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-exha...
| Main Authors: | , , , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
| Published: |
National Academy of Sciences
2020
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| Online Access: | https://hdl.handle.net/1721.1/128226 |
| _version_ | 1811072408085331968 |
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| author | Noble, Charleston Min, John Olejarz, Jason Buchthal, Joanna Chavez, Alejandro Smidler, Andrea L. DeBenedictis, Erika A. Church, George M. Nowak, Martin A. Esvelt, Kevin Michael |
| author2 | Massachusetts Institute of Technology. Media Laboratory |
| author_facet | Massachusetts Institute of Technology. Media Laboratory Noble, Charleston Min, John Olejarz, Jason Buchthal, Joanna Chavez, Alejandro Smidler, Andrea L. DeBenedictis, Erika A. Church, George M. Nowak, Martin A. Esvelt, Kevin Michael |
| author_sort | Noble, Charleston |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T09:05:33Z |
| format | Article |
| id | mit-1721.1/128226 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T09:05:33Z |
| publishDate | 2020 |
| publisher | National Academy of Sciences |
| record_format | dspace |
| spelling | mit-1721.1/1282262022-09-30T13:23:09Z Daisy-chain gene drives for the alteration of local populations Noble, Charleston Min, John Olejarz, Jason Buchthal, Joanna Chavez, Alejandro Smidler, Andrea L. DeBenedictis, Erika A. Church, George M. Nowak, Martin A. Esvelt, Kevin Michael Massachusetts Institute of Technology. Media Laboratory 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. Burroughs Wellcome Fund (Grant IRSA 1016432) National Institute of Diabetes and Digestive and Kidney Diseases (Grant R00-DK102669-03) 2020-10-27T23:02:03Z 2020-10-27T23:02:03Z 2019-04 2017-09 2019-07-18T18:35:52Z Article http://purl.org/eprint/type/JournalArticle 0027-8424 1091-6490 https://hdl.handle.net/1721.1/128226 Noble, Charleston et al. "Daisy-chain gene drives for the alteration of local populations." Proceedings of the National Academy of Sciences 116, 17 (April 2019): 8275-8282 © 2019 National Academy of Sciences en http://dx.doi.org/10.1073/pnas.1716358116 Proceedings of the National Academy of Sciences Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf National Academy of Sciences PNAS |
| spellingShingle | Noble, Charleston Min, John Olejarz, Jason Buchthal, Joanna Chavez, Alejandro Smidler, Andrea L. DeBenedictis, Erika A. Church, George M. Nowak, Martin A. Esvelt, Kevin Michael Daisy-chain gene drives for the alteration of local populations |
| title | Daisy-chain gene drives for the alteration of local populations |
| title_full | Daisy-chain gene drives for the alteration of local populations |
| title_fullStr | Daisy-chain gene drives for the alteration of local populations |
| title_full_unstemmed | Daisy-chain gene drives for the alteration of local populations |
| title_short | Daisy-chain gene drives for the alteration of local populations |
| title_sort | daisy chain gene drives for the alteration of local populations |
| url | https://hdl.handle.net/1721.1/128226 |
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