Problem Formulation for Off-Target Effects of Externally Applied Double-Stranded RNA-Based Products for Pest Control.

Externally applied dsRNA-based biocontrol products may lead to off-target degradation of messenger RNA in target and non-target organisms. For the purposes of regulatory risk assessment of such products, producing a comprehensive catalog of any off-target effects using profiling methods is unnecessary and would be ineffective in supporting decision-making. Instead, problem formulation should derive criteria that indicate acceptable risk and devise a plan to test the hypothesis that the product meets those criteria. The key to effective risk assessment of dsRNA-based biocontrols is determining whether their properties indicate acceptable or unacceptable risk, not whether they arise from on- or off-target effects of dsRNA.