Grape growers in Mexico have a new tool to fight powdery mildew, a common fungal disease, after the country became the first in the world to approve the commercial sale of an RNA-based biofungicide.
Oifirax, developed by the U.S. company GreenLight Biosciences, uses RNA molecules to silence a gene essential for the survival of the disease-causing fungus Erysiphe necator. The Mexican government announced the product’s commercial approval on 12 August, following a 9-month regulatory process involving the country’s health, agricultural, and environmental authorities.
“It was a surprise,” says agronomist Mario Serrano of the National Autonomous University of Mexico (UNAM), who, like many experts in the field, was not aware that the Mexican government was considering approving this new technology for agricultural use. The decision, he says, “is scientifically and economically positive for the country.”
Scientists have spent more than a decade developing products to control pests and diseases using a process called RNA interference. First off the block were pesticides: In 2023 GreenLight released Calantha, which targets the Colorado potato beetle. The spray uses RNA molecules to block a specific gene that encodes a key protein in the beetle. When the larvae eat leaves that have been sprayed, the RNA makes it into their gut, where cellular machinery destroys the matching messenger RNA (mRNA) that contains the instructions for creating the protein, killing the beetle.
The company’s new fungicide works in a similar way. It targets CYP51, a gene conserved among various fungal species that is involved in producing a crucial compound called ergosterol. When sprayed on grapes affected by powdery mildew, it prevents E. necator from producing ergosterol, causing its cell membranes to break down. This prevents the fungus from growing and ultimately leads to its death.
Oifirax has proved effective in eliminating E. necator without harming species such as monarch butterflies, honey bees, and earthworms, GreenLight CEO Andrey Zarur said during the press conference announcing the approval. He said the company submitted a bioinformatics analysis showing Oifirax doesn’t affect other soil organisms or vertebrates, and that Mexico’s regulatory agency will continue to conduct rigorous studies to ensure its safety.
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Preventing Oifirax from affecting other beneficial fungus species such as Trichoderma, endophytes, and decomposer fungi is “the complicated part,” says geneticist Damien Formey of UNAM. Although the CYP51 gene is widely conserved among fungi, the mRNA sequences targeted by Oifirax’s RNA molecules contain regions that are likely unique to E. necator. “That is the key to the specificity of RNA fungicides,” he says. However, without knowing the genomic sequences of every species and strain where the product will be applied, “we cannot be 100% sure that it will not affect other organisms,” he says. “The probability is low, but not zero.”
At the company’s press conference, GreenLight announced it also plans to invest between $50 million and $100 million in a plant in Mexico City to mass-produce Oifirax. Production is one of the main obstacles for RNA-based products worldwide, Serrano says, because of the complexity of producing and purifying specific RNA sequences consistently, as well as the high production costs compared with chemical fungicides. The fungicide’s mass production in Mexico is the company’s “real novelty,” he says.
In recent years, the Mexican government has promoted a shift toward more sustainable agriculture and the use of alternatives to chemical pesticides. Oifirax’s approval “is a very good sign,” says biotechnologist Jorge Humberto Ramírez-Prado of the Center for Scientific Research of Yucatán. “It means that they [the government] are open to working with more new technologies,” he says.
Serrano hopes to see the country invest more in fungicide research. “These are very powerful tools, but this is not the end of the story,” he says, “but rather a step forward in improving RNA-based technology.”