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Spraying RNAi To Silence Target Genes In Crops (And Insect Pests)…

Many object to GMO crop plants, at least in part, because they contain foreign genes artificially – and permanently – inserted into the plant’s genome.

But what if you could TEMPORARILY modifY plants (and even their insect pests) by simply spraying little bits of genetic material on the leaves?

These aren’t really GMO crop plants….are they? If they aren’t, then one of the main reasons that governments and the public object to GMO’s would be eliminated. And this may be why such technology has recently attracted the attention of the plant biotech community, especially Monsanto.

According to Dr. Robert Fraley, Monsanto Chief Technology Officer, Monsanto’s so-called BioDirect™ technology (see Ref. 1 below) “…has the potential to be one of the most exciting advancements for agriculture that I’ve seen in my career”. And since Fraley has been at Monsanto for over 30 years, if what he says is true, then this is a pretty big deal, and we should understand how it works.

A good place to start is a recent article published in the MIT Technology Review (please see Ref. 2 below). And several other excellent articles that’ll help bring you up to speed on the subject are Refs. 3, 4 & 5 below.

But if you don’t want to wade in so deep right now, please allow me to present the basic story…

…very simply put, the idea is to spray on plants relatively small bits of genetic material (in this case, small, distinct strands of RNA) that very specifically turn off the production of certain gene products (mainly, proteins). This may be potentially lethal in some cases, for example, if a critical enzyme is turned off in insect pests on the plants (for example, see YouTube video below), or if an enzyme that confers herbicide tolerance is turned off in noxious weeds.

This technology is based on a number of genetic discoveries that were first made about 20 years ago, now collectively referred to as “RNA interference”.

RNA interference (RNAi) is a biological process in which RNA molecules inhibit gene expression, typically by causing the destruction of specific mRNA molecules. Historically, it was known by other names, including co-suppression, post transcriptional gene silencing (PTGS), and quelling. Only after these apparently unrelated processes were fully understood did it become clear that they all described the RNAi phenomenon. Andrew Fire and Craig C. Mello shared the 2006 Nobel Prize in Physiology or Medicine for their work on RNA interference in the nematode worm Caenorhabditis elegans, which they published in 1998.” (from Wikipedia)

Brief aside: Some felt that the Nobel committee ignored vital groundwork on RNAi in plants and that at least one plant biologist should have shared the 2006 Nobel. (Please see previous post on why few plant scientists have won the Nobel Prize.)

Anyway, back to the subject at hand… spraying RNA on plants…

To me (and others), it’s quite remarkable that this actually works, for several reasons. The first reason has to do with the fact that RNA is very unstable. Chemically and biologically, RNA is significantly more labile than DNA. And RNA is very expensive to synthesize in the quantities that would be required for this proposed technology.

Another reason, as pointed out by Monsanto’s Dr. Fraley “…no one yet understands exactly how to get RNA inside a plant’s cells using a field sprayer—at least not with the sort of inexpensive, works-every-time efficiency farmers would be looking for. Many insects are also not easily affected. Monsanto has been spending millions to crack these problems, collaborating with biotech companies specializing in drug delivery. “We’re still a few breakthroughs away,” he says.” (from Ref. 2 below)

One such drug delivery company is Apse, Inc. (see Ref. 6 below), which, according to their website, “…has developed technology that will allow the cost efficient production of RNA for broad acre topical RNAi uses in agriculture.

But overcoming these technological issues is not the only problem faced by spraying RNA on plants.

…And Praying That This Technology Is Approved (And Accepted By The Public)

In the past couple of years, both the US Environmental Protection Agency (EPA) and the European Food Safety Authority (EFSA) have published reports dealing with the possible risks to the environment and human health from agricultural RNAi technology.

“The EPA’s advisors, in their report last year, agreed that there was little evidence of a risk to people from eating RNA. But is there some kind of ecological risk? This question they found harder to answer. Monsanto paints RNA as safe and quick to disappear, yet the aim is to make it lethal to insects and weeds, and the company wants to develop longer-lasting formulations. How long? In Hunter’s trees [see YouTube video below] the molecules persisted for months. What’s more, Monsanto’s own discoveries have underscored the surprising ways in which double-stranded RNA can move between species.
These unfolding discoveries suggest that complex biology is at work, leading the EPA’s advisors to say that the “potential scale” of RNA used in agriculture “warrants exploration of the potential for unintended ecological effects.” RNA may be natural. But introducing large amounts of targeted RNA molecules into the environment is not. The advisory panel concluded that “knowledge gaps make it difficult to predict” exactly what problems might arise.”
(from Ref. 2 below)

From the 2014 EFSA workshop report: “Genetically modified plants intended for market release can be designed to induce silencing of target genes in planta or in insect pests through RNA interference. As part of the pre-market risk assessment, the European Food Safety Authority evaluates any risks that genetically modified plants may pose to animal and human health and the environment. To discuss potential risks associated with RNA interference-based genetically modified plants and to identify issues unique to their risk assessment, the European Food Safety Authority organised an international scientific workshop on 4-5 June 2014 in Brussels (Belgium), bringing together experts from academia, risk assessment bodies, non- governmental organisations and the private sector. The workshop considered the molecular biology underlying the RNA interference mechanism, current and future applications of RNA interference- based genetically modified plants, and risk assessment aspects. During the workshop, risk assessment aspects were discussed in three separate break-out sessions, each focusing on one of the three main areas of genetically modified plant risk assessment: molecular characterisation; food/feed safety assessment; and environmental risk assessment. The objective of the workshop was to solicit scientific expertise for the problem formulation phase of the risk assessment of RNA interference-based genetically modified plants. An overview of the presentations given, remarks made and discussion points put forward during the workshop are presented and summarised in this report.” (Please see Ref. 7 below)

A lot of money is resting on the approval and acceptance of this technology: “Both Monsanto and Syngenta have invested heavily in RNAi technology over the last couple years. Monsanto acquired an Israeli company that uses RNAi to improve plant traits, as well as a pharmaceutical company with major intellectual property in RNAi research. Meanwhile, Syngenta purchased Devgen, a leader in RNAi crop protection.” (from Ref. 3 below)

Bottom Line: Agricultural spraying of RNAi has many significant challenges to overcome, not the least of which is governmental and public acceptance.

Online References

1. BioDirect™ – Monsanto

2. Antonio Regalad, “The Next Great GMO Debate.” MIT Technology Review (online) August 11, 2015. (Full Text)

3. Jackie Robin “RNA interference: Big potential for agriculture.” Ag-WestBio (online) April 17, 2015. (Full Text)

4. Narender Nehra and Nigel Taylor “Improving Crops with RNAi.” The Scientist (online) June 1, 2015. (Full Text)

5. Andrew Pollack “Genetic Weapon Against Insects Raises Hope and Fear in Farming.” The New York Times (online) January 27, 2014. (Full Text)

6. Apse

7. European Food Safety Authority (2014) “International scientific workshop ‘Risk assessment considerations for RNAi-
based GM plants
’.” Full Text (PDF)

YouTube Video of Dr. Wayne Hunter briefly explaining how RNAi technology can be manipulated to kill psyllids in citrus groves.

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