Literature review of baseline information on non‐coding RNA (ncRNA) to support the risk assessment of ncRNA‐based genetically modified plants for food and feed

This report is the outcome of an EFSA procurement (NP/EFSA/GMO/2016/01) reviewing relevant scientific information on ncRNA and on RNA interference(RNAi) that could support the food and feed risk assessment of ncRNA‐based genetically modified (GM) plants. Information was retrieved through key words and key questions covering the stability and degradation of ncRNAs after oral ingestion, the passage of ncRNAs from food and feed to human and animal organs and tissues via the gastrointestinal tract and other barriers, as well as the potential effects on the gastrointestinal tract, the immune system or the entire organism.Full description of the strategy used for the literature search and for studies selectionis provided and the number of retrieved publications is reported. This report is divided into four partsdiscussing the kinetics of exogenous ncRNAs in humans and animals, with focus on ingested ncRNAs (Part 1); the possible effects of ncRNAs on the gastrointestinal tract (Part 2), systemically(Part 3)and on the immune system (Part 4). This report suggests that some plant ncRNAs (e.g miRNAs and siRNAs) show higher stability as compared to other ncRNAs due to peculiar chemical characteristics (2’‐O‐methylation at 3’ end).However, ingested or administered ncRNA must overcome many extracellular and cellular barriers to reach the intended target tissue or functional location in sufficient amount to exert any biological effect. Literature data indicate that chemically unmodified and unformulated ncRNAs exhibit very low stability in the gastrointestinal tract and in biological fluids and, in general, do not elicit major biological effects.This report also provides an overview of the RNA content in plant‐derived foods and diets and discusses the controversies on the presence of dietary exogenous RNAs in the biological fluids of humans and animals and their effects. Finally, gaps in the scientific literature are highlighted and recommendations provided