Programmable design of synthetic plant immune receptors for pathogen protein recognition.

The limited diversity and recognition scope of natural plant immune receptors impede resistance breeding against rapidly evolving pathogens. Here, we report the programmable design of synthetic plant immune receptors (SPIRs). De novo-designed binding modules targeting pathogen proteins were grafted into the integrated decoy domain of a plant immune receptor. SPIRs recognized proteins derived from viral, bacterial, fungal, and oomycete pathogens. Their performance was improved by combining artificial intelligence-guided protein design with in planta-directed evolution, enhancing immune activation while reducing autoactivation. The SPIRs exhibited high target specificity and could be stacked for multiplexed recognition of pathogen proteins. Viral-targeting SPIRs responded to infectious clones of plant viruses, and transgenic plants expressing SPIRs conferred disease resistance. This work establishes a versatile platform for the efficient engineering of plant immunity.