• Coleopteran vs. lepidopteran RNAi disparities linked to SID-1 polymorphism and dsRNase evolution. • Microbial dsRNA vs regulatory fragmentation (EPA/EFSA) limits access. • Nano-encapsulation extends dsRNA half-life overcoming instability barriers for topical dsRNA. • RNAi-Bt combos delay but dsRNase/SID-1 adaptations risk sustainability. • CRISPR + pheromone delivery for ecology-sensitive smallholder solutions. Global food security faces unprecedented challenges from population growth, climate change, and pest-related crop losses. Conventional pest management strategies, reliant on synthetic pesticides and Bacillus thuringiensis (Bt) toxins, are undermined by widespread resistance evolution and ecological collateral damage. RNA interference (RNAi) has emerged as a transformative biotechnology, exploiting sequence-specific gene silencing to target pest vulnerabilities while minimizing non-target impacts. This review synthesizes advances in RNAi-based pest control, focusing on molecular mechanisms, delivery modalities, and translational challenges. Mechanistically, RNAi operates through enzyme-processed small RNAs that guide protein complexes to complementary mRNAs, inducing degradation or translational repression. We critically analyze taxonomic variability in RNAi efficacy, where coleopterans show high sensitivity (LC 50: 0. 1 ng/cm 2) but lepidopterans require 100–1000 × higher doses due to dsRNase activity and limited systemic spread. Commercial milestones include SmartStax® PRO maize (>95% root protection) and Ledprona™ spray (80–90% efficacy against Colorado potato beetle). Key barriers persist as production economics (1. 2/g microbial vs. 50/g synthetic dsRNA), environmental stability (14d nano-encapsulated dsRNA), regulatory heterogeneity (EPA vs. EFSA frameworks), and evolving resistance. Future integration with CRISPR-mediated gene drives and pheromone attractants could establish RNAi as the cornerstone of precision pest management within sustainable agriculture frameworks.
Hussain et al. (Wed,) studied this question.