Exploiting a Y chromosome-linked Cas9 for sex selection and gene drive

Author:

Gamez StephanieORCID,Chaverra-Rodriguez DuverneyORCID,Buchman AnnaORCID,Kandul Nikolay P.,Mendez-Sanchez Stelia C.ORCID,Bennett Jared B.ORCID,Sánchez C. Héctor M.ORCID,Yang TingORCID,Antoshechkin IgorORCID,Duque Jonny E.ORCID,Papathanos Philippos A.,Marshall John M.ORCID,Akbari Omar S.ORCID

Abstract

AbstractCRISPR-based genetic engineering tools aimed to bias sex ratios, or drive effector genes into animal populations, often integrate the transgenes into autosomal chromosomes. However, in species with heterogametic sex chromsomes (e.g. XY, ZW), sex linkage of endonucleases could be beneficial to drive the expression in a sex-specific manner to produce genetic sexing systems, sex ratio distorters, or even sex-specific gene drives, for example. To explore this possibility, here we develop a transgenic line of Drosophila melanogaster expressing Cas9 from the Y chromosome. We functionally characterize the utility of this strain for both sex selection and gene drive finding it to be quite effective. To explore its utility for population control, we built mathematical models illustrating its dynamics as compared to other state-of-the-art systems designed for both population modification and suppression. Taken together, our results contribute to the development of current CRISPR genetic control tools and demonstrate the utility of using sex-linked Cas9 strains for genetic control of animals.

Funder

United States Department of Defense | Defense Advanced Research Projects Agency

Division of Intramural Research, National Institute of Allergy and Infectious Diseases

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry

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