Just over 20 years since the RNA interference (RNAi) mechanism was unraveled in the nematode Caenorhabditis elegans, the first RNAi-based pest control applications are close to commercialization. One of the most alluring aspects of this technology is its predicted minimal impact on the environment, due to high target selectivity and the short persistence of the active molecules in the environment. However, gaps of knowledge on the RNAi mechanism in many species and their implications for biosafety still exist. In this review, we present a comprehensive overview of the research conducted in this field. We discuss potential in planta and topical application methods in the field and their consequences regarding potential exposure in different non-target organisms (NTOs). While RNAi is assumed to be highly species selective, due to its sequence-guided mode of action, dsRNA design will determine how selective a product is. We also discuss molecular and cellular mechanisms affecting RNAi efficacy and how these could become a basis for the emergence of resistance against RNAi-based control products and highlight the need for resistance management. Finally, we briefly discuss recommendations for environmental risk assessment (ERA), such as the value of bioinformatics and the development of properly designed bioassays to predict effects in NTOs or to select NTOs for informing ERA.

自从在线虫秀丽隐杆线虫 中的 RNA 干扰 (RNAi) 机制被解开 20 多年以来，第一个基于 RNAi 的害虫控制应用已接近商业化。该技术最吸引人的方面之一是它预计对环境的影响最小，因为它具有高目标选择性和活性分子在环境中的短暂持久性。然而，关于许多物种的 RNAi 机制及其对生物安全的影响的知识差距仍然存在。在这篇综述中，我们全面概述了在该领域进行的研究。我们讨论植物的潜力和该领域的局部应用方法及其对不同非靶标生物 (NTO) 潜在暴露的影响。虽然 RNAi 被认为具有高度的物种选择性，但由于其序列引导的作用模式，dsRNA 设计将决定产品的选择性。我们还讨论了影响 RNAi 功效的分子和细胞机制，以及这些机制如何成为对基于 RNAi 的对照产品产生抗性的基础，并强调抗性管理的必要性。最后，我们简要讨论了环境风险评估 (ERA) 的建议，例如生物信息学的价值以及开发适当设计的生物测定以预测 NTO 的影响或选择 NTO 以告知 ERA。