Abstract

Engineered gene drives based on a homing mechanism could rapidly spread genetic alterations through a population. However, such drives face a major obstacle in the form of resistance against the drive. In addition, they are expected to be highly invasive. Here, we introduce the Toxin-Antidote Recessive Embryo (TARE) drive. It functions by disrupting a target gene, forming recessive lethal alleles, while rescuing drive-carrying individuals with a recoded version of the target. Modeling shows that such drives will have threshold-dependent invasion dynamics, spreading only when introduced above a fitness-dependent frequency. We demonstrate a TARE drive in Drosophila with 88-95% transmission by female heterozygotes. This drive was able to spread through a large cage population in just six generations following introduction at 24% frequency without any apparent evolution of resistance. Our results suggest that TARE drives constitute promising candidates for the development of effective, flexible, and regionally confinable drives for population modification.

CRISPR homing gene drives are highly invasive and can fail due to the rapid evolution of resistance. Here the authors present TARE drive, inspired by naturally occurring selfish genetic elements, which is less vulnerable to resistance and can potentially be confined to a target population.

Details

Title
A toxin-antidote CRISPR gene drive system for regional population modification
Author
Jackson, Champer 1   VIAFID ORCID Logo  ; Lee, Esther 1 ; Yang, Emily 1 ; Liu, Chen 1 ; Clark, Andrew G 1   VIAFID ORCID Logo  ; Messer, Philipp W 2   VIAFID ORCID Logo 

1  Cornell University, Department of Computational Biology, Ithaca, USA (GRID:grid.5386.8) (ISNI:000000041936877X); Cornell University, Department of Molecular Biology and Genetics, Ithaca, USA (GRID:grid.5386.8) (ISNI:000000041936877X) 
2  Cornell University, Department of Computational Biology, Ithaca, USA (GRID:grid.5386.8) (ISNI:000000041936877X) 
Publication year
2020
Publication date
2020
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-020-14960-3
ProQuest document ID
2366606712
Copyright
This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.