Abstract

BACKGROUND Tribolium castaneum is a major pest that affects stored grains globally. RNA insecticides present a promising strategy for the management of insect pests; however, they encounter challenges in target gene discovery, cost and efficiency. The paramyosin ( PM ) gene has shown potential as a target for RNAi-based insecticides. This study aims to explore the potential of ZIF-8@ds TcPM complexes as an RNA insecticide, assessing their effectiveness in targeting the TcPM gene while ensuring stability and protection of dsRNA. RESULTS This study discovered that the PM gene exists throughoutthe life cycle of T. castaneum and is predominantly located in adult muscle tissues. The ds TcPM notably downregulated TcPM gene expression, causing high mortalities in larvae and adults. The PM gene was highly conserved across diverse insect orders but absent in vertebrates, suggesting that the RNA insecticides targeting this gene may offer broad-spectrum control of insect pests with mammalian safety. The L4440-HT115 produced functional ds TcPM efficiently (2.15 μg mL −1 ) via fermentation under optimized conditions (0.8 m m IPTG at 37 °C for 6 h). ZIF-8 can spontaneously form stable complexes with ds TcPM with an average particle size of 125.64 nm to effectively protect ds TcPM from nuclease and hemolymph degradation. ZIF-8@ds TcPM not only exhibited safety for HEK293T cells, but also demonstrated significant toxicity to adult T. castaneum via the feeding method, with a mortality of 62.22% on the ninth day post-treatment. CONCLUSION This work demonstrates that the ZIF-8@ds TcPM offers a promising option for the effective prevention and sustainable control of T. castaneum . © 2026 Society of Chemical Industry.