Overview of polymeric polyplexes for dsRNA delivery in insects: complexation, stability, and design considerations

Polymer-based delivery systems for double-stranded RNA (dsRNA) have gained attention as a promising strategy for RNA interference (RNAi)-mediated insect pest control. Despite encouraging <i>in vitro</i> results, their practical application remains limited by methodological inconsistencies and species-specific challenges. Variability in experimental parameters, such as nitrogen/phosphorous (N/P) ratios, dsRNA lengths, and buffer systems, complicates reproducibility and cross-study comparisons. Moreover, <i>in vitro</i> stability and transfection efficiency often fail to predict <i>in vivo</i> RNAi outcomes, highlighting the need for more physiologically relevant models. Variation in RNAi efficiency across insect orders, such as Lepidoptera and Hemiptera, continues to challenge the generalizability of polymer-based delivery systems. To advance the field, future research should focus on species-tailored polymer design, improved predictive assays, and comprehensive environmental safety evaluations. Interdisciplinary collaboration will be essential to develop RNAi delivery platforms that are efficient, scalable, and ecologically sustainable.