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Further scientific comment on new miRNA study

Details
Published: 16 September 2015
Twitter

Longstanding natural life processes are not equivalent to new GMO products, scientist says

Recently we reported on a new study (abstract below) that found that some miRNA molecules – minute fragments of plant genetic material that can silence genes – present in maternal breastmilk are not taken up into mice tissues.

These results contrast with findings published in 2012 by a Chinese team of researchers, which found that miRNA molecules from rice were taken up into the blood and organs of mice that ate the rice, where they regulated the expression of certain genes and affected the animals’ physiological processes.

This was an alarming paper for the biotech industry, which is heavily focused on developing new GMO products using miRNA and dsRNA (double-stranded RNA) molecules and wants them to be accepted as safe. These new GMO products may include insecticidal crop sprays that work by silencing the genes of insects, as well as GM crops containing engineered miRNA molecules.

Clearly the industry does not want the perception (or knowledge) to gain ground that these products could silence or interfere with the gene expression of “off-target organisms” such as human or animal consumers – as suggested by the 2012 Chinese team’s findings.

In our report on the new would-be reassuring study, we published a comment by Dr Sarah Agapito, a research scientist at Genøk, Norway. Dr Agapito said that just because two out of a possible 500 miRNAs in the diet were not taken up, it doesn’t rule out the possibility that other miRNAs could be taken up.

Now GMWatch has received a further scientific comment on the new study. Dr Michael Antoniou, a London-based molecular geneticist, emphasized that the miRNAs examined in the new study are natural miRNAs with a long history of safe use, unlike novel miRNA products engineered by the GMO industry. Dr Antoniou said of the study:

“They’ve investigated a natural process – breastfeeding of infants – which has evolved not to pose harm and to nourish the infant.

“The analysis conducted by the authors, to see whether miRNAs present in breast milk enter the tissues of the infant, does not address the concerns raised by the use of novel miRNAs that will be sprayed onto the crop as insecticides or engineered into the crop plant itself. It does not tell us whether these novel classes of miRNA in a completely different food matrix can be taken up by the organs of the animal or human consumer – or whether if they are taken up, they are safe.”

Dr Antoniou’s comment reinforces Dr Agapito’s view that we should not be reassured by the new study.
—

Uptake and function studies of maternal milk-derived microRNAs

Alexandra C. Title, Rémy Denzler and Markus Stoffel
J. Biol. Chem. 2015, Published Aug 3, 2015
http://www.jbc.org/content/early/2015/08/03/jbc.M115.676734.abstract
(open access)

Background: It is unclear whether maternal milk microRNAs are taken up by offspring.
Results: Milk microRNAs are not taken up into murine offspring tissues or blood, but are degraded by the digestive system.
Conclusion: It is unlikely that milk microRNAs function through canonical microRNA silencing.
Significance: Nutritionally derived microRNAs are unlikely to cross the intestinal barrier and influence gene expression.

ABSTRACT
MicroRNAs (miRNAs) are important regulators of cell-autonomous gene expression that influence many biological processes. They are also released from cells and are present in virtually all body fluids, including blood, urine, saliva, sweat, and milk. The functional role of nutritionally obtained extracellular miRNAs is controversial, and irrefutable demonstration of exogenous miRNA uptake by cells and canonical miRNA function is still lacking. Here we show that miRNAs are present at high levels in milk of lactating mice. To investigate intestinal uptake of miRNAs in newborn mice, we employed genetic models in which newborn miR-375 and miR-200c/141 knockout mice received milk from wildtype foster mothers. Analysis of intestinal epithelium, blood, liver and spleen revealed no evidence for miRNA uptake. miR-375 levels in hepatocytes were at the limit of detection and remained orders of magnitude below the threshold for target gene regulation (between 1000 and 10,000 copies/cell). Furthermore, our study revealed rapid degradation of milk miRNAs in the intestinal fluid. Together, our results indicate a nutritional rather than gene regulatory role of miRNAs in milk of newborn mice.

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