RNA Interference Sprays as an Alternative to Transgenic Agriculture

A current focus of agricultural research is the development of RNA interference (RNAi) technology. An article on the MIT Technology Review site titled ‘The Next Great GMO Debate‘ was recently posted and is worth reading to understand some of the basics behind the technology and what biotechnology companies are trying to do with it.

RNAi is a naturally occurring defence mechanism present in most organisms including humans and plants. The mechanism is initiated when double stranded RNA (RNA being the message copied from DNA and which will be used as the instruction to create proteins in the cell – here’s a Youtube video with an overview) is found in a cell. Many viral genomes and some internal genetic elements are dsRNA and their presence in the cell can disrupt normal cell operation. An enzyme within the cell called ‘Dicer’ processes these dsRNA, cutting them into short pieces. A second enzyme, the RNA Induced Silencing Complex (RISC) uses one strand (the antisense strand) of the cut dsRNA as a template to seek out other dsRNA with a complementary RNA sequence. If this complex binds a complementary RNA fragment it either destroys or inhibits expression of it, reducing any damage that dsRNA may cause in the cell (see figure below and this neat youtube video).

RNAi_pathway

After its discovery it was quickly noted that inserting a dsRNA into a cell with a complementary sequence to one of the cell’s own normal RNA could be used to ‘knockout’ whatever protein that RNA contained the instructions for. For example, if dsRNA was inserted with a complementary sequence to a RNA that codes a protein for flower colour, the colour of the flower could be altered.

Applying this new information to agriculture, RNAi is being tested as an alternative to traditional insecticides and transgenic (genetically modified) plants which create their own insecticides. By constructing a library of a particular pest’s genome and constructing a dsRNA peculiar to a vital gene in that pest, this mechanism can be used to eliminate it using it’s own Dicer and RISC machinery. Importantly, the gene chosen can be very specific to that pest, potentially avoiding problems of unintended effects on other species of insects.

Research is also being conducted in how to use RNAi to alter crop qualities. For example, an article in the Plant Biotechnology Journal published on 24 August 2015 tested the ability of RNAi to down-regulate the expression of gluten protein in wheat for the benefit of those with gluten intolerances. Unfortunately I couldn’t find an open source copy of the article, so the abstract is here.

Although there are methods of introducing genes into an organism which will then produce the desired dsRNA, the research described in the MIT article is focused on the idea of being able to spray dsRNA targeted to a particular pest or a particular plant trait onto crops, allowing for quick, short term treatment.

Studies (here and here for example) have shown that the dsRNA can be ingested by some insect pests orally or by topical application suggesting that its use as an insecticide able to be applied to a crop can be successful. How a topical application enters cells and which mechanisms it uses to reach target cells remains a topic of research.

What hasn’t been shown yet, and what the biotech companies are working on, is the ability to spray dsRNA onto crops and have the crops take up the genetic material, allowing alteration of cellular processes simply. Whilst it has been shown that genes can be inserted into plants to create a specific dsRNA, being able to provide the same result without adding a gene and regrowing the plant will provide quick, specific advantage to the plant to protect itself from whichever environmental pressure is on it at the time such as a particular pest or reduced water availability.

Although the potential of quickly addressing such issues in agriculture in a non-permanent way is exciting, there are some negatives that have been detailed in an article by Professor Vicki Vance (available here. I found it on the Genetic Literacy Project site here).

Evolutionary arms races produce mutations that allow some species to overcome or reduce the silencing effect of the Dicer and RISC mechanisms. Given the number of viruses that may be present in crop pastures, some viruses may provide an immunity from RNAi effects of any additional dsRNA introduced into the plant.

Professor Vance also notes the concern that dsRNA consumed with food have been shown to travel to other parts of the body and may have unintentional silencing effects on parts of the consumer (or other non-target organisms).

Others who were interviewed in the MIT article either found they could replicate the findings of RNAi spray effectiveness, others commented that the sprays do not take immediate effect, which may result in a particular pest or environmental stress causing too much damage before the RNAi can assist it, and a similar concern about unintended effects but on non-target populations was expressed.

It seems that there is a lot of potential for RNAi sprays to progress our ability to manage pests and competing plants or increasing crop yields in whichever manner is required by the particular circumstances a crop is facing. The ability to increase water retention through hot spells to save water or to alter the protein make up of crop to suit a certain end-user could be of huge potential as climate change and population growth puts more pressure on crop producers. The specificity of a particular dsRNA will need to undergo some vigorous assessment to reduce or eliminate the possibility that it will find a similar sequence in the consumer and cause unwanted side-effects, but this is surely not to great an advance given our ability to sequence specific genes and compare them to our own for possible matches.

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