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Title: Safeguarding CRISPR-Cas9 gene drives in yeast

Abstract

RNA-guided gene drives capable of spreading genomic alterations made in laboratory organisms through wild populations could be used to address environmental and public health problems. However, the possibility of unintended genome editing occurring through the escape of strains from laboratories, coupled with the prospect of unanticipated ecological change, demands caution. In this, we report the efficacy of CRISPR-Cas9 gene drive systems in wild and laboratory strains of the yeast Saccharomyces cerevisiae. Furthermore, we address concerns surrounding accidental genome editing by developing and validating methods of molecular confinement that minimize the risk of unwanted genome editing. We also present a drive system capable of overwriting the changes introduced by an earlier gene drive. These molecular safeguards should enable the development of safe CRISPR gene drives for diverse organisms.

Authors:
 [1];  [2];  [3]; ORCiD logo [4];  [5]
+ Show Author Affiliations
  1. Harvard Medical School, Boston, MA (United States). Dept. of Genetics; Boston Univ., MA (United States). Dept. of Biomedical Engineering
  2. Harvard Medical School, Boston, MA (United States). Dept. of Genetics; Wyss Inst. for Biologically Inspired Engineering, Boston, MA (United States); Massachusetts General Hospital, Boston, MA (United States). Dept. of Pathology
  3. Harvard Medical School, Boston, MA (United States). Dept. of Genetics; Wyss Inst. for Biologically Inspired Engineering, Boston, MA (United States); ETH Zurich, Basel (Switzerland). Dept. of Biosystems Science and Engineering
  4. Harvard Medical School, Boston, MA (United States); Wyss Inst. for Biologically Inspired Engineering, Boston, MA (United States)
  5. Harvard Medical School, Boston, MA (United States). Dept. of Genetics; Wyss Inst. for Biologically Inspired Engineering, Boston, MA (United States)
Publication Date:
Research Org.:
Harvard Univ., Cambridge, MA (United States)
Sponsoring Org.:
USDOE; National Science Foundation (NSF); National Institutes of Health (NIH)
OSTI Identifier:
1466972
Grant/Contract Number:  
FG02-02ER63445; SynBERC SA5283-11210; MCB-1330914; 5T32CA009216-34; 1K99DK102669-01
Resource Type:
Accepted Manuscript
Journal Name:
Nature Biotechnology
Additional Journal Information:
Journal Volume: 33; Journal Issue: 12; Journal ID: ISSN 1087-0156
Publisher:
Springer Nature
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

DiCarlo, James E., Chavez, Alejandro, Dietz, Sven L., Esvelt, Kevin M., and Church, George M. Safeguarding CRISPR-Cas9 gene drives in yeast. United States: N. p., 2015. Web. doi:10.1038/nbt.3412.
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DiCarlo, James E., Chavez, Alejandro, Dietz, Sven L., Esvelt, Kevin M., & Church, George M. Safeguarding CRISPR-Cas9 gene drives in yeast. United States. doi:10.1038/nbt.3412.
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DiCarlo, James E., Chavez, Alejandro, Dietz, Sven L., Esvelt, Kevin M., and Church, George M. Mon . "Safeguarding CRISPR-Cas9 gene drives in yeast". United States. doi:10.1038/nbt.3412. https://www.osti.gov/servlets/purl/1466972.
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@article{osti_1466972,
title = {Safeguarding CRISPR-Cas9 gene drives in yeast},
author = {DiCarlo, James E. and Chavez, Alejandro and Dietz, Sven L. and Esvelt, Kevin M. and Church, George M.},
abstractNote = {RNA-guided gene drives capable of spreading genomic alterations made in laboratory organisms through wild populations could be used to address environmental and public health problems. However, the possibility of unintended genome editing occurring through the escape of strains from laboratories, coupled with the prospect of unanticipated ecological change, demands caution. In this, we report the efficacy of CRISPR-Cas9 gene drive systems in wild and laboratory strains of the yeast Saccharomyces cerevisiae. Furthermore, we address concerns surrounding accidental genome editing by developing and validating methods of molecular confinement that minimize the risk of unwanted genome editing. We also present a drive system capable of overwriting the changes introduced by an earlier gene drive. These molecular safeguards should enable the development of safe CRISPR gene drives for diverse organisms.},
doi = {10.1038/nbt.3412},
journal = {Nature Biotechnology},
number = 12,
volume = 33,
place = {United States},
year = {2015},
month = {11}
}
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Journal Article:
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Publisher's Version of Record
DOI:  10.1038/nbt.3412
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Cited by: 53 works
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Works referenced in this record:

Genome engineering in Saccharomyces cerevisiae using CRISPR-Cas systems
journal, March 2013

  • DiCarlo, James E.; Norville, Julie E.; Mali, Prashant
  • Nucleic Acids Research, Vol. 41, Issue 7, p. 4336-4343
  • DOI: 10.1093/nar/gkt135

One-Step Generation of Mice Carrying Mutations in Multiple Genes by CRISPR/Cas-Mediated Genome Engineering
journal, May 2013

RNA-Guided Human Genome Engineering via Cas9
journal, January 2013

Multiplex Genome Engineering Using CRISPR/Cas Systems
journal, January 2013

RNA-programmed genome editing in human cells
journal, January 2013

  • Jinek, Martin; East, Alexandra; Cheng, Aaron
  • eLife, Vol. 2, Article No. e00471
  • DOI: 10.7554/eLife.00471
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