EPA registers biopesticide containing ledprone

The U.S. Environmental Protection Agency (EPA) has registered biopesticide products containing ledprone (CAS 2433753-68-3, IRAC 35) for three years. This is a new type of pesticide, trademarked Calantha, developed by GreenLight Biosciences. As the EPA stated, "this technology replaces more toxic chemical pesticides, provides an additional tool for farmers to meet the challenges of climate change, and helps manage resistance."

Agency scientists explain that ledprone is a sprayable double-stranded ribonucleic acid (dsRNA) product that targets the Colorado potato beetle (Leptinotarsa ​​decemlineata), one of the main pests of potato crops grown in the United States. This coleoptera is an important pest of potato crops in Colorado, Idaho, Maine, Michigan, Minnesota, North Dakota, Oregon, Washington and Wisconsin.

The pesticide's active ingredient is a double-stranded ribonucleic acid (dsRNA) molecule with a gene silencing mode of action (i.e., RNA interference or RNAi). RNA is present in all living organisms, where they serve essential gene regulatory functions (e.g., transfer RNA, messenger RNA, micro RNA), and RNAi is a mechanism present in many eukaryotic organisms where it regulates gene expression and provides a defense against transposable elements and RNA-based viruses by targeting them for degradation.

ledprona exploits the RNAi machinery of Leptinotarsa ​​decemlineata to specifically regulate a protein essential for the survival of the organism. Specifically, ledprone was designed to target the mRNA sequence encoding the coleopteran Proteasome subunit type 5 beta gene (PSMB5). Once ingested by the beetle, ledprone is processed by the cellular RNAi machinery into small interfering molecules (siRNA - 21-23 nucleotides in length). These sequences are then selected and incorporated into the beetle's RNA-induced silencing complex (RISC), resulting in the downregulation of the PSMB5 protein, essential for survival.

In simpler terms, a scientific study showed that "Calantha (product with active ingredient ledprone) works by preventing the removal of damaged proteins, leading to the accumulation of poly-ubiquitinated proteins in the beetle's cells." As a consequence, unwanted proteins are not degraded and accumulate, damaging the body.

According to the EPA, this RNAi-based pesticide is the "world's first sprayable dsRNA pesticide authorized for commercial use and spraying on plants."

Leptinotarsa ​​decemlineata feeds on potato foliage. If left unchecked, it destroys the plant's leaves. If this occurs at flowering time, ultimately the plant may not produce potatoes. L. decemlineata quickly develops resistance to insecticides.

Conventional active ingredients registered and recommended for foliar use against Leptinotarsa ​​decemlineata in the United States include the neonicotinoids (e.g., thiamethoxam), the spinosyns, abamectin, novaluron (an insect growth regulator), the diamides (e.g., cyanotraniliprole), and some premixes thereof (e.g., abamectin and cyanotraniliprole). .

In May 2023, the EPA approved an experimental use permit under the Federal Insecticide, Fungicide, and Rodenticide Act for testing in 10 states (Idaho, Maine, Michigan, Minnesota, New York, North Dakota, Oregon, Virginia, Wisconsin, Washington). In September 2023, EPA opened a public comment period for this registration proposal.

The EPA said it has considered the comments received and believes it "has all the information necessary to support its decision to register this new biopesticides technology."