Application of food and feed safety assessment principles to evaluate transgenic approaches to gene modulation in crops.

New crop varieties containing traits such as enhanced nutritional profiles, increased yield, and tolerance to drought are being developed. In some cases, these new traits are dependent on small RNAs or regulatory proteins such as transcription factors (TF) that modify the expression of endogenous plant genes. To date, the food and feed safety of genetically modified (GM) crops has been assessed by the application of a set of internationally accepted procedures for evaluating the safety of GM crops. The goal of this paper is to review the main aspects of the current safety assessment paradigm and to recommend scientifically sound principles for conducting a safety assessment for GM crops that are developed by technologies that modify endogenous plant gene expression. Key considerations for such a safety assessment include the following: (1) RNA and TF are generally recognized as safe (GRAS); (2) Genes encoding RNAi and regulatory proteins such as TFs are an important component of the plantgenome; (3) Crops engineered using RNAi modifications are not expected to produce heterologous proteins; (4) The modulation of TFs may result in quantitative differences in endogenous plant components,which can be assessed through agronomic performance and compositional analysis on a caseby-case basis.