Synergistic RNA interference in pest management: Targets, synergistic mechanisms, and integrated design strategies

RNA interference (RNAi) is a specific pest-control technology, yet its standalone application is limited by issues of low efficiency, instability, and high cost. This review aims to build a framework for "RNAi synergistic enhancement" to overcome these hurdles, with a core strategy of combining RNAi with synergistic agents. In this context, five key target pathways amenable to RNAi intervention-neural transmission, energy metabolism, cuticle synthesis, immunity, and detoxification networks-are summarized, and some categories of synergistic agents (such as chemical/botanical pesticides, insect growth regulators, and biocontrol microorganisms) are proposed to achieve a "1 + 1 > 2" effect. Subsequently, a synergistic RNAi paradigm is introduced, from a simple mixture to nano-fusion co-assembly, encompassing the screening of synergistic factors, assembly mechanisms, and their control efficacy. Finally, the transformation from pursuing isolated efficacy to designing programmable "synergistic systems" is discussed, which requires addressing integrated challenges, including temporal action coordination, carrier biocompatibility, comprehensive risk assessment, and the establishment of tailored regulatory standards. This review provides a systematic blueprint for developing the next generation of efficient and sustainable RNA-based synergistic pesticides.