Kuku8CRISPR/Cas9-mediated TOP1 knockout in Chicken DF-1 cells reveals its critical role in apoptosis regulation and genomic stability

Abstract

Lay Summary Chick culling in poultry farming raises ethical and sustainability concerns, driving the need for humane sex-control technologies. This study used CRISPR/Cas9 to knockout the Topoisomerase I (TOP1) gene in chicken cells, discovering that TOP1 loss induces DNA damage and cell death. While not a direct sex-control method, these findings identify TOP1 as a potential target to selectively eliminate male-determining cells by using the principle of synthetic lethality. The research lays groundwork for a future approach: integrating TOP1-editing components into chicken chromosomes to generate single-sex offspring (only hens or rooster), reducing culling needs. By addressing the root problem of sex-based culling, this work advances a sustainable, ethical strategy for poultry production, providing critical insights for developing targeted gene-editing solutions in birds.