Location: Children's Nutrition Research CenterTitle: Bioavailability of transgenic microRNAs in genetically modified plants Author
|Yang, Jian - Children's Nutrition Research Center (CNRC)|
|Primo, Cecilia - Children's Nutrition Research Center (CNRC)|
|Elbaz-younes, Ismail - Children's Nutrition Research Center (CNRC)|
|Hirschi, Kendal - Children's Nutrition Research Center (CNRC)|
Submitted to: Genes and Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/18/2017
Publication Date: 7/7/2017
Citation: Yang, J., Primo, C., Elbaz-Younes, I., Hirschi, K.D. 2017. Bioavailability of transgenic microRNAs in genetically modified plants. Genes and Nutrition. doi:10.1186/s12263-017-0563-5.
Interpretive Summary: Genetically modified (GM) crops are subject to an environmental risk-assessment process designed to evaluate their safety. Expression of small nucleic acids is now a popular approach in agbiotechnology for the global enhancement of foods. However, expression of these small nucleic acids is not currently regulated. Here we characterize the bioavailability of some transgenic small nucleic acids in mouse feeding studies. We used genomic and pharmacological methods to rigorously show that these transgenic nucleic acids are not bioavailable. This work informs regulatory agencies about the safety of consuming transgenic plant foods expressing engineered small nucleic acids.
Technical Abstract: Transgenic expression of small RNAs is a prevalent approach in agrobiotechnology for the global enhancement of plant foods. Meanwhile, emerging studies have, on the one hand, emphasized the potential of transgenic microRNAs (miRNAs) as novel dietary therapeutics and, on the other, suggested potential food safety issues if harmful miRNAs are absorbed and bioactive. For these reasons, it is necessary to evaluate the bioavailability of transgenic miRNAs in genetically modified crops. As a pilot study, two transgenic Arabidopsis lines ectopically expressing unique miRNAs were compared and contrasted with the plant bioavailable small RNA MIR2911 for digestive stability and serum bioavailability. The expression levels of these transgenic miRNAs in Arabidopsis were found to be comparable to that of MIR2911 in fresh tissues. Assays of digestive stability in vitro and in vivo suggested the transgenic miRNAs and MIR2911 had comparable resistance to degradation. Healthy mice consuming diets rich in Arabidopsis lines expressing these miRNAs displayed MIR2911 in the bloodstream but no detectable levels of the transgenic miRNAs. In conclusions, these preliminary results imply digestive stability and high expression levels of miRNAs in plants do not readily equate to bioavailability. This initial work suggests novel engineering strategies be employed to enhance miRNA bioavailability when attempting to use transgenic foods as a delivery platform.