A Y-chromosome shredding gene drive for controlling pest vertebrate populations.

Thomas AA Prowse,Fatwa Adikusuma,Joshua V Ross,Paul Thomas,Phillip Cassey

doi:10.7554/elife.41873

Thomas AA Prowse, Fatwa Adikusuma + Show 3 more

Open Access

https://doi.org/10.7554/elife.41873

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Abstract

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.

Highlights

The engineering of ‘selfish’ gene drives, with biased inheritance (Burt, 2003), has become increasingly feasible since the advent of the CRISPR/Cas9 genome-editing system (Esvelt et al, 2014; Gantz and Bier, 2015; Champer et al, 2016; Galizi et al, 2016; Hammond et al, 2016; Kyrou et al, 2018)
Expression of Cas12a and each of the guide RNA (gRNA) in XY mouse embryonic stem cells resulted in deletion of the Y-chromosome with high efficiency compared to cells transfected with empty vector (EV) (Figure 2)
We show for the first time that the CRISPR/Cas12a system can be utilized to delete the Y chromosome in cultured cells derived from the early murine embryo

Summary

Introduction

The engineering of ‘selfish’ gene drives, with biased inheritance (Burt, 2003), has become increasingly feasible since the advent of the CRISPR/Cas genome-editing system (Esvelt et al, 2014; Gantz and Bier, 2015; Champer et al, 2016; Galizi et al, 2016; Hammond et al, 2016; Kyrou et al, 2018). By spreading genetic elements through the genomes of wild populations, this technology could be used to address a range of environmental problems, including the control of invasive (or overabundant) sexually reproducing animal populations (Prowse et al, 2017; McFarlane et al, 2018).

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