DOI: 10.1111/rda.70286 ISSN: 0936-6768

Precision Genome Editing in Domestic Animals: A New Era for Agriculture and Medicine

Mariana Sponchiado, Paula Mangiavacchi, Bethany K. Redel, Kiho Lee

ABSTRACT

Precision genome editing technologies have transformed the generation and application of genetically engineered livestock, positioning domestic animals as powerful models for agriculture, biomedicine, and basic research. Historically, genetic engineering in livestock was constrained by the absence of embryonic stem cells, low efficiency of homologous recombination, long gestation periods, and extended generation intervals. The advent of programmable nucleases, including zinc finger nucleases, transcription activator‐like effector nucleases, and CRISPR–Cas systems, has overcome many of these barriers by enabling efficient targeted genome modification. This review focuses on the application of genome editing technologies in mammalian livestock species, with pigs highlighted as a representative model. We discuss the historical development of livestock genetic engineering and summarise two main routes used to establish genome edited livestock models. Key technical considerations unique to domestic animals are also presented. Genome editing has accelerated the production of livestock models for human disease, xenotransplantation, reproductive biology, and agricultural improvement, including disease resistance, altered growth traits, and enhanced product composition. Emerging epigenome editing strategies further expand the toolkit by allowing locus‐specific gene regulation without permanent DNA modification. Despite rapid technological progress, challenges remain, including mosaicism, off‐target effects, limited ability to segregate unintended edits, and ethical and regulatory concerns surrounding food and biomedical applications. Continued refinement of genome editing strategies will be essential for maximizing the utility and responsible implementation of genome‐edited livestock. Overall, precision genome editing represents a transformative platform with broad implications for sustainable agriculture, translational research, and global food security.