Summary of Discussions From the 2019 OECD Conference on RNAi Based Pesticides

Abstract

RNA interference (RNAi) is a biological process in which double-stranded ribonucleic acid (dsRNA) molecules inhibit protein expression. In recent years, the application of dsRNA has been used in the development of agricultural products for pest control. The 2019 Organisation for Economic Cooperation and Development (OECD) Conference on RNAi Based Pesticides ("the Conference") brought together academic, industry, and government experts in various aspects of RNAi to discuss the current state of knowledge and topics to help in developing considerations for risk assessment. The Conference focused on environment, with some discussion of human health. Along with presentations on the use of dsRNA-based products in agriculture, government regulation, risk assessment, and a background on the Draft OECD Working Paper on "Considerations for the Environmental Risk Assessment of the Application of Sprayed or Externally Applied dsRNA-Based Pesticides" ("OECD Working Paper"), the Conference included panel discussions from presenters at the end of each session and a larger discussion session with Conference participants on the environmental fate of dsRNA, non-target organism (NTO) risk assessment, and human health risk assessment. This paper summarizes input from presenters and Conference participants during these discussions. Key considerations from these discussions have already been incorporated into the OECD Working Paper, that once finalized and published, will facilitate regulators in evaluating externally applied dsRNA-based products for potential environmental risks.

Advances and Challenges in RNA Interference Technology for Citrus Huanglongbing Vector Control

“…To date, however, there are methods to quantify the reliability of these bioinformatic software in assessing such off-target effects. Given the variability in environmental exposure, barriers to systemic exposure, and differences in RNAi machinery among organisms, the bioinformatic software as the sole tool is not recommended [74,76,77]. Specialists from the academic, industrial, and government sectors have discussed several aspects of RNAi, with particular focus on furthering our knowledge of the technology for risk assessment [18,78].…”

“…The conference held by the Organization for Economic Cooperation and Development covered multiple perspectives related to RNAi-based pesticides. The potential exposure of NTOs and responsiveness to environmental RNAi have been discussed as the main parameters to be considered in the risk assessment of exogenous dsRNA application, and appropriate legislation involving risk assessment procedures in science-based topical RNAi-based applications must be enacted (Figure 2) [76].…”

Emerald Ash Borer Specific Gene Silencing Has No Effect on Non-target Organisms

“…Pan et al (2016) identified six 21nt long matches between dsRNA targeting the vATPase A in D. virgifera and the springtail Sinella curviseta (Collembola: Entomobryidae), yet the springtail was not adversely affected in laboratory feeding assays. In our study, silencing genes other than the target indicates that the RNAi response was not a sequence-specific event, but a generalized immune response to dsRNA, leading Mendelsohn et al (2020) to suggest that the use of bioinformatics may have limited value in assessing off-target effects due to interspecific variation in RNAi machinery and variability in environmental exposure across different organisms.…”

“…To move a biopesticide using RNAi technology toward commercialization, its risk to the environment and possible adverse effects on non-target organisms must be evaluated (Vélez et al, 2016;Haller et al, 2019). Given the novel mode of action of dsRNA-based products, the regulatory requirements for their deployment have been discussed internationally (USEPA, 2014;Mendelsohn et al, 2020;Romeis and Widmer, 2020). The risk assessment framework currently in use for genetically engineered plants expressing insecticidal proteins, such as those expressing Cry proteins from Bacillus thuringiensis, has been suggested as a starting point to evaluate the potential hazards for RNAi products (Romeis et al, 2013;Romeis and Widmer, 2020).…”

Advances in the Development of Microbial Double-Stranded RNA Production Systems for Application of RNA Interference in Agricultural Pest Control

“…Moreover, the engineered microbes may spread into the environment, and lead to sustainable expression of dsRNA, which might affect non-target species in the environment. Besides, plasmid-based expression elements may be transferred inter-species, resulting in biological contamination problems ( Mendelsohn et al, 2020 ). dsRNA produced in engineered bacteria cannot be secreted directly outside the cell.…”