Off-Target Effects of Plant Transgenic RNAi: Three Mechanisms Lead to Distinct Toxicological and Environmental Hazards. (Report compiled in 2010 for The Bioscience Resource by Jonathan R. Latham, PhD and Allison K. Wilson). Tables for the report can be found at: RNAi BiosafetyTables.
Recent developments in the application of RNA interference (RNAi) to plants mean that the introduction of transgenes with defined sequences can now routinely result in the inhibition of target RNAs and therefore gene activity. Consequently, there are now greatly enhanced opportunities for the use of this technology in agriculture and speciality crops. Applications demonstrated so far include the manipulation of plant metabolism and behavior, and resistance to pathogenic bacteria, viruses, insects, and other invertebrates. Realization of this potential, however, will ultimately depend on the specificity with which transgene-derived RNAs act. Specificity is important within the crop plant itself but also towards exposed non-target organisms such as beneficial insects and mammals. There has been little discussion of off-target effects (OTEs) arising from plant transgenic RNAi. This review considers three classes of potential plant RNAi OTEs: (1) OTEs leading to non-specific downregulation of plant RNAs; (2) OTEs affecting non-target invertebrates feeding on plant material and; (3) potential effects on mammals. In mammals, long (>30bp) perfectly duplexed RNAs (such as are typically produced by plant RNAi transgenes) are Pathogen Associated Molecular Patterns (PAMPS) and are consequently highly potent triggers of innate anti-viral defenses. The effects of long dsRNAs on mammalian cellular functions are typically profound and extend to complete inhibition of protein translation and cell death. Nevertheless, the implications of such molecules in the mammalian diet have yet to be tested.