Mexico has approved the sale of the world's first fungicide that uses the principle of ribonucleic acid interference (RNA interference, RNAi). It is Oifirax, developed by U.S.-based GreenLight Biosciences. The Mexican government said on the 12th (local time) that it approved commercial sales of the product after a nine-month regulatory review involving health, agriculture and environmental authorities.
RNA interference refers to blocking gene expression with RNA strands. The genetic information in deoxyribonucleic acid (DNA) is transcribed as needed into messenger ribonucleic acid (mRNA), which produces proteins involved in various life processes. Some RNA fragments, instead of making proteins, bind to other mRNA. That, in turn, blocks the function of the genes that the mRNA transcribed.
Oifirax uses RNA molecules to kill the pathogenic fungus that causes grape powdery mildew (scientific name Erysiphe necator). When infected with powdery mildew, hyphae and spores cover the fronts and backs of leaves like flour, hindering photosynthesis. If grape berries are infected, the skin loses elasticity, cracks and eventually dries up or rots.
The gene Oifirax targets is CYP51, which makes ergosterol, a component of the cell membrane. When sprayed on grapevines infected with powdery mildew, double-stranded RNA (dsRNA) enters the fungus. The RNA is then cut into short interfering RNA (siRNA), which seeks out and degrades the mRNA that transcribed the CYP51 gene's information. The fungus cannot produce ergosterol, can no longer grow and dies.
The issue is that the CYP51 gene also exists in other fungi. In principle, that means Oifirax could be capable of killing other fungi as well. Damien Formey, a professor at the National Autonomous University of Mexico, said, "The most challenging part is ensuring that Oifirax does not affect beneficial fungal species that aid plant growth and health or decompose plants and animal waste to provide nutrients."
GreenLight said it designed RNA strands that selectively degrade only the mRNA of the powdery mildew fungus. The genetic information of DNA or RNA varies depending on the order in which the four bases are arranged. Formey said, "The mRNA that Oifirax's RNA molecules bind to includes a base sequence unique to the powdery mildew fungus."
GreenLight CEO Andrey Zarur said at a press conference hosted by the Mexican government that Oifirax removes only the powdery mildew fungus without harming other organisms essential to crops, such as butterflies, bees and earthworms. Zarur said the company submitted bioinformatics analyses showing Oifirax does not affect other soil microorganisms or vertebrates, and that Mexican regulators will continue to study the product to confirm its safety.
RNA interference was first used in medicine. The 2006 Nobel Prize in physiology or medicine went to two scientists who uncovered the RNA interference phenomenon in which short RNA regulates gene function. Since the U.S. Food and Drug Administration (FDA) first approved a new drug for a rare disease using RNA interference in 2018, six have been approved as therapies to date.
Development of RNA interference pesticides is also active. Monsanto, a seed company acquired by Germany's Bayer, bought the Israeli startup Beeologics in 2011. Beeologics developed technology that uses RNA interference to prevent parasitic infections in bees. Beeologics' RNA interference technology was transferred to GreenLight in 2021.
In 2023, GreenLight launched Calantha, a pesticide that uses RNA interference to control the Colorado potato beetle. The Colorado potato beetle is a pest that causes severe damage by chewing the leaves and stems of Solanaceae crops such as potatoes and eggplants. Calantha uses RNA molecules to block genes essential for the beetle's survival. When larvae eat leaves sprayed with the pesticide, the RNA enters the gut, where it degrades mRNA.
In Korea, Genolution developed HoneyGuard-R solution, an RNA interference therapy that prevents the sacbrood virus, a major cause of mass bee colony deaths, and received approval from the Ministry of Agriculture, Food and Rural Affairs in June 2024. Sacbrood is a viral infectious disease known as "bee AIDS" that infects larvae. In 2010, this virus spread in Korea and 90% of native bees disappeared. HoneyGuard-R solution was designated a government innovative product in April and entered the public procurement market.
References
Mexican government portal, https://www.gob.mx/se/prensa/participacion-del-secretario-de-economia-marcelo-ebrard-durante-el-evento-mexico-lider-en-biotecnologia?idiom=es-MX