Self-replicating gene drives that modify sex ratios or infer a fitness cost could be used to control populations of invasive alien species. The targeted deletion of Y sex chromosomes using CRISPR technology offers a new approach for sex bias that could be incorporated within gene-drive designs. We introduce a novel gene-drive strategy termed Y-CHromosome deletion using Orthogonal Programmable Endonucleases (Y-CHOPE), incorporating a programmable endonuclease that ‘shreds’ the Y chromosome, thereby converting XY males into fertile XO females. Firstly, we demonstrate that the CRISPR/Cas12a system can eliminate the Y chromosome in embryonic stem cells with high efficiency (c. 90%). Next, using stochastic, individual-based models of a pest mouse population, we show that a Y-shredding drive that progressively depletes the pool of XY males could effect population eradication through mate limitation. Our molecular and modeling data suggest that a Y-CHOPE gene drive could be a viable tool for vertebrate pest control.
https://www.geneconvenevi.org/wp-content/uploads/2020/04/eLife-1.png300300Academic Web Pages/wp-content/uploads/2019/10/GC-color-logo-for-header-3277-x-827-1030x260.pngAcademic Web Pages2019-01-16 00:00:002020-04-22 16:33:40A Y-chromosome shredding gene drive for controlling pest vertebrate populations