Risk assessment considerations for ncRNA in agricultural products and applications

Jan Verhaert (and Jay S. Petrick), Monsanto, Belgium

The RNA interference (RNAi) pathway has been recognised in crops for over a decade. Recent advances in technology have lead to advances in agricultural applications based on the RNAi pathway. RNA-based traits are the basis for phenotypes in conventional crops, with soybean seed coat colour and maize stalk colour serving as examples of RNA-based gene regulation harnessed through selective breeding (Tuteja et al, 2004; Della Vedova et al, 2005; Koseki et al, 2005). In addition, RNA-based technologies have been successfully employed to introduce new traits in crops, such as virus resistance, altered oil composition in soybeans, and insect protection against corn rootworm. These types of traits have been risk assessed and approved by multiple regulators across the globe. RNA has an extensive history of safe consumption and humans and animals routinely consume small RNAs and longer double stranded RNAs in staple foods that have 100% sequence identity to the consuming human or animal without impact to health (Ivashuta et al, 2009; Jensen et al, 2013; Frizzi et al, 2014). This safe consumption results in part from extensive barriers to ingested RNAs, such as low gut pH, nucleases, multiple membrane barriers, and rapid renal elimination of RNA (Petrick et al, 2013). These barriers are also evidenced by drug delivery challenges faced by developers of oligonucleotide-based drugs (Juliano et al, 2009; O’Neill et al, 2011; Petrick et al, 2013). Further studies in mammals indicate that ingested double-stranded RNAs, even those targeting a gene in the test species, do not produce adverse health effects in these animals (Petrick et al, 2015). Whereas RNA-based technologies provide new tools to address agricultural challenges, the overall weight-of-evidence including historical knowledge as well as new empirical evidence shows that these technologies are safe and fall within the current safety assessment process.