Targeted protein and protein-condensate degradation in plant science research and crop breeding.

Abstract

Gene expression can be modulated at DNA, RNA, or protein levels, with targeted protein degradation (TPD) representing a well-established and effective strategy for manipulating protein function. TPD enables the selective elimination of proteins, protein condensates, or organelles via cellular degradation pathways, such as the ubiquitin-proteasome system, autophagy, or endocytosis, through induced proximity mechanisms. While TPD has had a transformative impact in biomedical research over the past two decades, its applications in plant science research has lagged behind. This gap stems from the dominance of RNA interference and CRISPR technologies, as well as the complexity and cost of 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 offer a plant-adaptable, precise, tunable, and conditional means for controlling 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 plant biology research and agricultural applications. 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, especially GE-CPDs, in advancing plant science. We argue that the field is well-positioned to harness the full potential of TPD for next-generation crop improvement.