Engineering plant immune receptors for programmable and broad-spectrum disease resistance

Plants rely on immune receptors to perceive pathogens and activate defense responses, yet naturally evolved receptors are often constrained by limited recognition spectra, pathogen adaptation, and fitness trade-offs. Recent advances in structural biology, protein engineering, and synthetic biology have enabled the rational redesign of plant immune receptors beyond their evolutionary constraints. Here, we review engineering strategies for two major immune receptor classes, nucleotide-binding leucine-rich repeat receptors (NLRs) and pattern recognition receptors (PRRs). NLR engineering has expanded effector recognition through modification of recognition domains, integrated decoy redesign, artificial binder incorporation, and conditional activation switches, whereas PRR engineering has broadened pathogen perception through receptor transfer, domain recombination, ligand optimization, and synthetic receptor discovery. Beyond receptor recognition, engineering immune signaling components provides additional opportunities to optimize immune outputs and improve resistance durability. We further discuss how exogenous chemical inputs can provide an external layer for conditional activation of engineered immune receptors, enabling immune responses to be tuned while potentially reducing growth costs associated with constitutive defense. Integrating receptor engineering with chemical control and computational design may ultimately enable broad-spectrum, precisely controlled and agronomically relevant disease resistance.