Silencing resistance: RNAi as a next-generation strategy for combating insecticide resistance

Insecticides play a pivotal role in safeguarding global agricultural productivity and food security. However, decades of intensive and indiscriminate use led to the rapid evolution of insecticide resistance. Its development is driven by diverse mechanisms, including target-site insensitivity, metabolic detoxification, reduced penetration, sequestration, behavioural resistance, etc., which often act synergistically. Conventional insecticide resistance management strategies, such as rotation of different insecticides and refugia strategies, have shown limited, long-term success against agriculturally important insect pests. In this scenario, RNA interference (RNAi), a sequence-specific, gene silencing mechanism, has emerged as a powerful molecular tool for functional genomics, pest management, including its potential in combating resistance to insecticides. Recent advancements in delivering double-stranded RNA targeting insecticide resistance genes, such as cytochrome P450 monooxygenases, glutathione S-transferases and carboxylesterases, aimed at restoring susceptibility to insecticides, brings about a paradigm shift in insecticide resistance management. This review provides a new line of synthesis on the current knowledge on insecticide resistance mechanisms and critically examines RNAi-based strategies in resistance management suppression. It also discusses the delivery platforms, integrating suitable insecticides, biosafety considerations and prospects for RNAi-assisted resistance management for sustainable agriculture.