Implementation of RNAi-based arthropod pest control: environmental risks, potential for resistance and regulatory considerations

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.