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Betting on RNAi as the new Wave of Crop Protection Solutions

Betting on RNAi as the new Wave of Crop Protection Solutions

By Emily Harwitz

 

The spotted bronze head and shiny black-and-yellow-striped wings of the Colorado potato beetle are an unwelcome sight for farmers. Though larvae and adults feed primarily on potato plants, the Colorado potato beetle also eats other plants in the Solanaceae family, otherwise known as the nightshades, famed for the potent alkaloid content in their leaves.

To cope with eating the toxic leaves of these plants, the beetle has evolved mechanisms to metabolize toxins, including chemical pesticides. This ability has helped it become the world’s biggest potato pest since spreading from the Southwest US in the 1850s.

Russ Groves, a professor and extension specialist in the University of Wisconsin–Madison’s Entomology Department, has been studying insecticide resistance in agricultural systems for decades and says the potato growers he works with are all too familiar with the beetle’s special ability. “So if your question is, ‘Do Colorado potato beetles generate resistance?’ ” he says, the answer is, “Oh my God, yes.”

To overcome insecticide resistance, some in the agriculture industry are now betting on a new class of chemicals called RNA interference (RNAi) pesticides. One of the companies working on them is GreenLight Biosciences, which is poised to go public in the next few months in a deal that could value it at $1.2 billion. Scientists have been working on RNAi pesticides for over a decade. Many in the industry think the pesticides are now ready to move agriculture to a kind of crop protection that is more effective and less harmful to the environment.

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Some sources say the first successful application of an agrochemical occurred in the 1860s when farmers managed to kill the potato beetleby spraying Paris green, or cuprous acetoarsenite, onto their fields. But the beetle is legendary for its ability to develop resistance to insecticides. That includes more modern chemicals such as the neonicotinoid imidacloprid, which has been making news for its devastating impact on pollinators.

Mechanical methods, like plowing a deep trench between last season’s potato crop and the new one, can thwart the potato beetle. When the beetle larvae emerge in the spring from the old field, some of them will fall into the trench and get trapped. Growers can also flame their fields using propane-powered jets of fire that heat the plants up hot enough to annihilate beetles without killing the more heat-resistant potato plants. But these methods can be inefficient and don’t easily scale up.

The beauty of RNAi, proponents say, is that it’s very specific and less likely to harm other insects, plants, and animals than conventional broad-spectrum pesticides are. It also leaves little environmental impact since RNA degrades easily into amino acids.

RNAi technology is based on an evolutionary response to viruses. In living organisms, single-stranded messenger RNA (mRNA) translates genetic code into proteins. Viruses have double-stranded RNA (dsRNA) that they inject into host cells to replicate, a process which includes making mRNA. When a cell encounters the dsRNA of a virus, the cell initiates a defense by chopping it up into tiny pieces. Other organelles in the cell then search for any strands of mRNA that match the pieces of dsRNA and chop them up as well, thus preventing viral proteins from being made.

Around 2006, when the discovery of the process won two scientists the Nobel Prize in Physiology or Medicine, researchers began working on ways to harness this natural response to target pathogens or pests. They figured that introducing the right dsRNA into a target pest would cause the pest to chop up its own mRNA. The sequence must be unique to that pest and code for a protein that’s necessary for the organism’s survival. The most common formulation being developed is a dsRNA-containing spray meant to coat the leaves of plants the pest is going to ingest.

Determining which unique nucleotide sequence to encode in the dsRNA is “something that can be done partially bioinformatically” by comparing the genomes of the insect with other organisms in the same ecosystem, says Marko Petek, who researches transcriptomics, or gene expression, at the National Institute of Biology in Slovenia. The next step is testing the dsRNA in the lab to see how the pest processes it after ingestion, Petek explains, and to ensure that no nontarget organisms are affected.

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