A confinable home and rescue gene drive for population modification
- University of California, San Diego, United States
- University of California, Berkeley, United States
Abstract
Homing based gene drives, engineered using CRISPR/Cas9, have been proposed to spread desirable genes throughout populations. However, invasion of such drives can be hindered by the accumulation of resistant alleles. To limit this obstacle, we engineer a confinable population modification Home-and-Rescue (HomeR) drive in Drosophila targeting an essential gene. In our experiments, resistant alleles that disrupt the target gene function were recessive lethal, and therefore disadvantaged. We demonstrate that HomeR can achieve an increase in frequency in population cage experiments, but that fitness costs due to the Cas9 insertion limit drive efficacy. Finally, we conduct mathematical modeling comparing HomeR to contemporary gene drive architectures for population modification over wide ranges of fitness costs, transmission rates, and release regimens. HomeR could potentially be adapted to other species, as a means for safe, confinable, modification of wild populations.
Data availability
All data are represented fully within the tables and figures. The gRNA#1PolG2, gRNA#2PolG2, HomeRPolG2, HomeR(B)PolG2, exuL-Cas9, Rcd1r-Cas9, and βTub-Cas9 plasmids and corresponding fly lines are deposited at Addgene.org (159671-159677) and the Bloomington Drosophila Stock Center (91375-91378), respectively.
Article and author information
Author details
Funding
Defense Advanced Research Projects Agency (HR0011-17-2-0047)
- Omar S Akbari
National Institutes of Health (R21RAI149161A)
- Omar S Akbari
National Institutes of Health (R01AI151004)
- Omar S Akbari
National Institutes of Health (DP2AI152071)
- Omar S Akbari
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2021, Kandul 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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