That is, the hemizygous plants
may express a smaller amount of the intended dsRNA molecules than homozygous plants. However, UFSC researchers have argued that ‘gene-dosage’ alone does not explain the difference in susceptibility levels. For instance, in Table V.17 of Aragão and Faria (2010b) data indicate a variety of susceptibilities for hemizygotes only. These plants would all have the same number of transgenes. The UFSC researchers then proposed three hypotheses that could explain the results obtained for the F1 plants: (i) instability or truncation of the insert; (ii) environment x gene interactions; or (iii) virus-mediated transgene silencing or resistance to silencing (Noris et al., 2004 and Taliansky et al., 2004). Testing these hypotheses would have provided the regulator with the biochemical explanation selleck compound of the varying levels of resistance and informed a risk management plan. However, CTNBio did not require the developer to address the varying susceptibility levels. Interestingly, the regulator appeared unaware of this variability because they concluded that the segregation pattern was what they expected and that the
observed phenotypes were normal in all crosses made (CTNBio, 2011). Although a few products based on dsRNA-mediated silencing have been approved, the commercialization history of these products is spotty. Flavr Savr Tomato, New Leaf Potatoes and the G series of high oleic acid soybeans were Anti-infection Compound Library in vitro withdrawn from market shortly after release (FSANZ, 2009b and Monsanto, 2001). The exceptions
are papaya and pinto beans which have been consumed on a relatively small basis. Given that few people would be exposed to artificial siRNAs, and exposed in low amounts through consuming currently approved products, it is not surprising that regulators from different countries have not established common, validated assessment procedures for these molecules (ACNFP, 2012 and Lusser et al., 2011). A validation process establishes both the relevance and reliability TCL of a test. Validation usually involves establishing the test definition, assessing the within- and between-laboratory variation in the results, the transferability of the test between laboratories, the predictive capacity of the test, how applicable the test is to the situation and how well the test conforms to certain standards (Hartung et al., 2004). Regulation of traits based on dsRNA in GMOs is therefore currently based on ad hoc standards and acceptance of unpublished studies conducted by GMO developers even though the approval of the first human food based on dsRNA-mediated silencing occurred nearly 20 years ago. The regulatory community is only now actively debating how these molecules should be assessed. There are also discordant statements about expected standards appearing in the literature.