Exploiting a Y chromosome-linked Cas9 for sex selection and gene drive.
Stephanie Gamez, Duverney Chaverra-Rodriguez, Anna Buchman, Nikolay P Kandul, Stelia C Mendez-Sanchez, Jared B Bennett, Héctor M Sánchez C, Ting Yang, Igor Antoshechkin, Jonny E Duque, Philippos A Papathanos, John M Marshall, Omar S Akbari
Nature communications · 2021-Dec-10 · PMID 34893590 · DOI 10.1038/s41467-021-27333-1Abstract
CRISPR-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.
Evidence profile
- Study type
- modeling
- Text reviewed by the copilot
- Full text is available
- Publication status
- published
- Corrections or retractions
- none
- Conflict statement
- O.S.A. is a founder of Agragene, Inc., and has an equity interest. The terms of this arrangement have been reviewed and approved by the University of California, San Diego in accordance with its conflict of interest policies. S.G. is currently affiliated with Agragene Inc. A.B. is currently affiliated with Verily Life Sciences. All other authors declare no competing interests.