Targeted Protein Degradation and Protein-condensate Degradation for Plant Science and Crop Breeding.

Abstract

Gene expression can be modulated at the DNA, RNA, or protein level, with targeted protein degradation (TPD) representing a well-established and effective strategy for directly manipulating protein function. TPD enables selective elimination of proteins, protein condensates or organelles by co-opting cellular degradation pathways-such as the ubiquitin-proteasome system, autophagy, or endocytosis-via induced proximity mechanisms. While TPD has had transformative impacts in biomedical research over the past two decades, its application in plant science has lagged behind. This gap stems from the sequential dominance of RNA interference and CRISPR technologies, as well as the complexity and cost of implementing chemical, macromolecular, and recombinant degrader platforms in plants. The recent development of genetically encoded chimeric protein degraders (GE-CPDs) offers a timely and promising alternative. These transgene-based systems provide a plant-adaptable, precise, tunable, and conditional means to control endogenous protein levels, opening new avenues for studying dynamic biological processes and engineering complex traits in crops. As genome engineering technologies continue to advance, GE-CPDs are poised to become a versatile and scalable platform for both basic plant biology and agricultural innovation. In this review, we highlight five key opportunities-Selective-Targeting, Co-Targeting, Organelle-Targeting, Conditional-Targeting, and Synthetic-Engineering (SCOCS)-that illustrate the emerging importance of TPD technologies, particularly GE-CPDs, in advancing plant science. We argue that the field is now well-positioned to harness the full potential of TPD for next-generation crop improvement.