Advancing herbicide safeners: Integrating structure-guided design, pathway mechanism elucidation, and smart delivery

Weeds threaten crop production, and while essential for control, they commonly cause crop damage. Herbicide safeners safeguard crops by selectively enhancing their detoxification pathways, without affecting herbicide efficacy. However, the rational design of safeners still remains a significant challenge. This review focuses on three core strategies for developing novel safeners: (i) structure-guided design, including the structural optimization of commercial and natural safeners; (ii) mechanism-driven design through integrated multi-omics and detoxification pathway analysis; (iii) enabling efficient delivery via advanced smart delivery systems. By integrating recent progress, this review proposes a strategic framework for developing effective, environmentally friendly safeners for current and future herbicides.