SfCYP6AN4-Mediated Spinetoram Resistance and RNA Pesticide Application in Spodoptera frugiperda

Globally, the invasive fall armyworm (Spodoptera frugiperda, FAW) has been characterized by the widespread development of tolerance to multiple insecticides, a process facilitated by extensive and prolonged exposure to these compounds. This study utilized RNA interference (RNAi) to explore the potential association of cytochrome P450 genes to spinetoram resistance in S. frugiperda, with the parallel aim of investigating nanocarrier-based P450-targeting formulations as synergistic agents for improved pest management. Bioassay results from Guangdong S. frugiperda populations revealed the highest tolerance in the Meizhou population (LC₅₀ = 0.673 µg/mL). Spinetoram exposure induced a 6.5 U/mL increase in larval P450 activity and triggered marked upregulation of CYP6AN4 (4.98-fold versus control), which exhibited concentration-dependent induction (2.52-fold under tested conditions). The LDH-dsCYP6AN4 + spinetoram formulation achieved 62.87% mortality, representing an 11.31% enhancement over the LDH + spinetoram group, and maintained robust synergy across diverse field populations. These phenotypic and molecular observations indicate that CYP6AN4 upregulation is closely correlated with the spinetoram response and may potentially contribute to altered insecticide susceptibility in field populations.