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Species-specific crop protection

RNA interference provides a new method of pest control, using tools so precise they hit only the target insect or disease

“We like to call sclerotinia the bully,” says Mark Belmonte. And stopping a bully is not easy. The pathogen attacks fast, it moves quickly through the plant and it can do heavy yield damage right away.

“Because it acts with brute force and involves multiple genes, sclerotinia is difficult to study and get a good understanding for control,” says Belmonte, researcher and associate professor at the University of Manitoba. “Sclerotinia is a complex infection that is good at eluding current fungicides, so we have to be more creative.”

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Belmonte’s lab focuses on developing new crop-protection tools using big data and next-generation genetic sequencing. He’s working on one particular method that will provide new solutions: RNA interference (RNAi).

Deoxyribonucleic acid (DNA), the long double-helix molecules repeated in all cells, contains the genetic codes for growth and function of an organism. Ribonucleic acid (RNA) picks up those codes and sends code-containing messages throughout the organism. DNA is the instruction book. RNA is the engineer who reads the instruction book and assigns the work that will build the proteins to keep the organism alive. If we sidetrack these critical assignments, we can stop the work (in the case of pests) or enhance the work (in the case of plant defence response). This sidetracking is the gist of RNAi.

Using algorithms

For his sclerotinia work, Belmonte profiles the genes expressed in the fungus and the response-genes activated within canola plants at the time of infection. “We have literally trillions of data points,” he says, “but within that huge haystack are needles that will work as targets for RNAi.”

It takes a certain amount of luck to find potential targets, but Belmonte and his team use algorithms to predict where the targets are within those numerous data points. It works.

They have found an RNAi-suitable target gene that controls a function necessary for sclerotinia survival. With that discovery, they then made an RNAi molecular fungicide that stops that function and kills the fungus.

So now what?

There are two choices. One, the RNAi molecule can be made into a foliar spray. Or two, a gene can be introduced into canola so the plant makes the RNAi molecule itself, using it to stop the fungus when it infects.

With a transgenic trait, the plant expresses the trait all the time so it’s ready to go when sclerotinia infects. That means no timing issues or “should I spray?” questions that farmers face every year with any foliar fungicide to prevent sclerotinia stem rot. A key disadvantage is the regulatory approval required to grow and sell a transgenic trait.

Advantages to the foliar spray are that it can be developed and marketed for use on a number of different crops and in various markets; new spray molecules can be screened within weeks to see if they work, and foliar spray is not transgenic. But while this is a new highly targeted mode of action, it presents many of the same timing issues and “should I spray?” questions that growers have with current fungicides. And, though transgenic approval is probably more difficult, RNAi sprays are also regulated and require approval from Health Canada and from key markets.

Regulations

André Gagnon, media relations officer with Health Canada’s Pest Management Regulatory Agency (PMRA), provides this statement:

“In Canada, pesticides are stringently regulated by Health Canada’s Pest Management Regulatory Agency (PMRA). Before a pest control product is approved for use in Canada, it must undergo a thorough science-based risk assessment and meet strict health and environmental standards. This includes the examination of both short- and long-term health effects. To reach its decisions, the PMRA applies modern, rigorous risk-assessment methods and policies.”

RNAi-based pest control products for use on crops are subject to these requirements, but Gagnon says they “may require different types of studies and may have conditions of use (e.g. restrictions) which differ from those of other pest control products.”

So far, no products using RNAi technology have been proposed to Health Canada for registration as pesticides in Canada.

Since Belmonte’s lab is one of many working on the technology, this is likely to change fairly soon.

Flea beetles

Monsanto has an RNAi-based foliar spray for flea beetles. “It builds on the flea beetle’s natural system of viral defence,” says Jim Baum, insect control mode-of-action strategy lead with Monsanto in St. Louis, Missouri. “Cells in the flea beetle’s mid-gut take it up, and this triggers a defence response that dials down production of essential proteins for life.”

Monsanto has seen success with this approach for various key pests within the coleoptera family. This includes corn rootworm, Colorado potato beetle and flea beetles. “RNAi molecules can be tailored to be specific to species within the same family, so one molecule can control flea beetles, but not corn rootworm or Colorado potato beetle,” Baum says. “There is no insecticide with that degree of specificity.”

Baum adds: “This is an entirely different mode of action that you don’t find with synthetic chemistry. We’re taking a naturally occurring molecule and directing it to the purpose.”

For flea beetles, death is not instant with the Monsanto RNAi spray. “It occurs within days of ingestion, but flea beetles do stop feeding well before they die,” Baum says. All of this will be part of the education as these products roll out.

Monsanto plans to introduce a corn rootworm product first, and follow with a flea beetle product. Because a lot of regulatory approvals are required in the meantime, the rough timeline, Baum says, is for commercial launch by the middle of the next decade.

Other companies are also on track with RNAi tools. Syngenta, to give another example, is focused on above-ground pests, which also includes foliar applications for flea beetles in canola.

Interestingly, the Syngenta approach is to be open with their early-stage data. “By sharing data on how RNA-based biocontrols are developed, we are encouraging and engaging in dialogue with scientists and researchers and looking to maximize the potential benefits for people generally, farmers and the environment,” says Chris Davison, head of corporate affairs for Syngenta Canada.

As research continues to demonstrate the environmental and economic value of biodiversity, including beneficial insects and beneficial fungi, next-generation RNAi molecules that affect only the target pest could represent a positive advance for agriculture.

“There is nothing random about RNAi,” says Mark Belmonte, “and there is no damage to off-target pests.”

About the author

Contributor

Jay Whetter is communications manager for the Canola Council of Canada.

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