For decades, pest control has relied heavily on the use of conventional chemical pesticides. Due to environmental concerns and the increasing emergence of resistance, crop protectors keep looking for novel and environmentally friendly control strategies. Recently, researchers demonstrated that RNA interference (RNAi), an eukaryotic gene silencing mechanism triggered by double-stranded RNA (dsRNA), can be exploited to control pests and diseases. dsRNA is a natural molecule with a short persistence in the environment and the sequence-specific mode of action could allow the design of highly species-selective pesticides, limiting harm on non-target organisms. However, there is still a great amount of uncertainty concerning these aspects, due to doubts about the necessary sequence homology for effective gene silencing, the effect of dsRNA exposure on the immune system of (beneficial) insects and the possibility for exposure through trophic chains. These aspects were also indicated in a systematic literature review the Smagghe lab recently coordinated for EFSA. In this project, we will investigate these important knowledge gaps in a fundamental and systematic way. The results of this project will provide researchers, industry and regulators with a much needed framework and tools for the development, risk assessment and regulation of these RNAi products. Furthermore, the data on dsRNA processing which will be obtained can also lead to improvements of RNAi-efficiency in insects.