A confinable home-and-rescue gene drive for population modification
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Mar 05, 2021
- Source ID
- 10.7554/elife.65939
Entities
People
- Jared B. Bennett
- John M Marshall
- Junru Liu
- Nikolay P. Kandul
- Omar S. Akbari
Organizations
- Defense Advanced Research Projects Agency
- National Institutes of Health
- University of California