RNAi: the next wave of green agriculture, challenges, and bridging the translational gap

Agriculture must achieve substantial yield gains while drastically reducing its environmental footprint to meet the food demands of a growing global population by 2050. Current crop losses to pests and pathogens account for 20-40% of annual production, a challenge predominantly addressed by chemical pesticides, which impose high ecological and health costs. RNA interference (RNAi) has emerged as a transformative, species-specific solution, demonstrating high efficacy (> 90%) against susceptible target pests under controlled laboratory conditions, though responsiveness varies considerably across taxa. However, the transition of RNAi to widespread field application has been slow. The first commercial RNAi-based crop trait targeting corn rootworm, MON 87411, was introduced as part of SmartStax PRO^® in 2022, followed by additional RNAi-enabled traits, such as Bayer's VT4PRO™, while spray-induced RNAi products have only recently entered the market, with Calantha becoming the first foliar-applied RNA-based biopesticide registered by the U.S. EPA in 2023. This review, synthesizing insights from over 250 studies, identifies three primary barriers limiting this translational transition: variable RNAi efficiency across species, the rapid environmental degradation of double-stranded RNA (dsRNA), and a fragmented regulatory landscape where products are variably classified as biochemical pesticides, plant-incorporated protectants, or novel active substances across jurisdictions. We highlight how emerging technological advances, including nanoparticle formulations for enhanced stability, microbial delivery systems, and cost-effective cell-free dsRNA production, are poised to overcome these hurdles. Furthermore, we position RNAi as a key tool for advancing sustainable food production and ecosystem health, aligning with multiple UN Sustainable Development Goals. By analyzing advances in molecular biology, formulation science, and environmental stability, this work provides a strategic framework for bridging the gap between laboratory promise and field-scale implementation, paving the way for RNAi to become a cornerstone of next-generation agriculture.