Molecular safeguarding of CRISPR gene drive experiments
- Cornell University, United States
Abstract
CRISPR-based homing gene drives have sparked both enthusiasm and deep concerns due to their potential for genetically altering entire species. This raises the question about our ability to prevent the unintended spread of such drives from the laboratory into a natural population. Here, we experimentally demonstrate the suitability of synthetic target site drives as well as split drives as flexible safeguarding strategies for gene drive experiments by showing that their performance closely resembles that of standard homing drives in Drosophila melanogaster. Using our split drive system, we further find that maternal deposition of both Cas9 and gRNA is required to form resistance alleles in the early embryo and that maternally-deposited Cas9 alone can power germline drive conversion in individuals that lack a genomic source of Cas9.
Data availability
All data generated are available in Supplementary file 2.
Article and author information
Author details
Funding
National Institutes of Health (R21AI130635)
- Jackson Champer
- Andrew G Clark
- Philipp W Messer
National Institutes of Health (F32AI138476)
- Jackson Champer
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Kevin M Esvelt, Massachusetts Institute of Technology, United States
Version history
- Received: August 25, 2018
- Accepted: January 9, 2019
- Accepted Manuscript published: January 22, 2019 (version 1)
- Version of Record published: February 1, 2019 (version 2)
Copyright
© 2019, Champer et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Molecular safeguarding of CRISPR gene drive experiments
eLife 8:e41439.
https://doi.org/10.7554/eLife.41439
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