Ledprona

Ledprone is an innovative molecule in the field of crop protection, classified as a double-stranded RNA (dsRNA)-based biopesticide.

It represents a breakthrough in sustainable agriculture, especially for pest control in potato crops, acting highly specifically against the Colorado potato beetle (Leptinotarsa ​​decemlineata, or CPB), one of the main pests that causes significant losses in Solanaceae crops.

Unlike traditional chemical insecticides, ledprone utilizes natural biological mechanisms, such as RNA interference (RNAi), minimizing impacts on non-target organisms and the environment.

Common name (ISO): Ledprona

Synonyms:

• RNA (Leptinotarsa ​​decemlineata-specific recombinant double-stranded interfering GS2)

• GS2 (development code)

• Calantha (trade name)

Gross formula: As a double-stranded RNA (dsRNA) molecule with 490 base pairs, ledprone has specific formulas for the sense and antisense strands:

Sense tape: C₄₄₀₉H₅₃₉₈N₁₇₉₄O₃₂₀₈P₄₆₀

Antisense tape: C₄₃₃₁H₅₃₈₅N₁₆₂₅O₃₂₃₄P₄₆₀

This structure is a recombinant oligonucleotide designed to interfere with specific CPB genes, with base sequences (adenine - A, cytosine - C, guanine - G and uracil - U) optimized for stability and efficacy.

Number CAS: 2433753-68-3

Chemical class: Biochemical biopesticide based on dsRNA (recombinant double-stranded RNA). It belongs to the RNAi (RNA interference) class of insecticides, differing from traditional chemical classes in that it is a large biological molecule that is not persistent in the environment.

Release year: Although registered by the United States Environmental Protection Agency (EPA) on December 22, 2023, commercial launch took place in 2024.

Development history: Ledprone was developed by GreenLight Biosciences, Inc., a biotechnology company based in Medford, Massachusetts (USA), focused on cell-free manufacturing platforms for the scale production of RNA molecules. Development began in the 2010s, driven by the need for alternatives to chemical insecticides to combat CPB resistance, which affects more than 80% of potato crops in the USA. Initial efficacy and mode-of-action studies were published in 2021, demonstrating larval mortality exceeding 90% in laboratory and field bioassays. In 2022, it was validated as a new action group (IRAC 35) by the Insecticide Resistance Action Committee (IRAC). The EPA granted an experimental permit in May 2023 for testing in 10 potato-producing states, followed by full registration in December 2023, with a waiver of tolerance for residues in potatoes. The Calantha product was approved in several states in January 2024, integrating into integrated pest management (IPM) programs for rotation with other insecticides.

Mode of action: Ledprone acts via RNA interference (RNAi), a natural defense mechanism used by plants and insects to silence unwanted genes. Specifically, it binds to the PSMB5 gene (proteasome beta-5 subunit) in the CPB, inhibiting the production of an enzyme essential for protein degradation. This leads to the accumulation of toxic metabolic waste in the beetle cells, causing paralysis, cessation of feeding, and mortality within 3–6 days. The process is highly specific: the dsRNA is ingested by the larvae, processed into small interfering RNAs (siRNAs) in the insect's gut, and does not affect vertebrates or other arthropods due to physiological barriers and rapid degradation (half-life <1 hour in simulated gastric fluids). Classified in IRAC group 35 (RNAi-mediated targeted suppressors), it is effective against populations resistant to chemical insecticides and promotes agricultural sustainability by degrading rapidly in the environment (with no detectable residues in soil, water or food).

Patent numbers: US 20200149044, WO 2020097414A1 and others.

Efficacy in field trials

Ledprone demonstrated high performance in several tests, exceeding expectations for a biopesticide. In laboratory bioassays, exposure to low doses (equivalent to 7–9 g of active ingredient per hectare) resulted in larval mortality exceeding 90% in all instances of the Colorado potato beetle (CPB), with a significant reduction in leaf consumption and mobility of adult insects.

In greenhouse trials on whole plants, ledprone performed equivalently to the chemical insecticide spinosad, a gold standard in pest control. Field trials conducted between 2019 and 2023, including tests by the University of Minnesota, confirmed that it limits potato defoliation in a manner comparable to conventional insecticides, with consistent protection against late-stage larvae.

In 2024-2025, additional studies validated its effectiveness under real-world growing conditions, including chemical-resistant populations, reinforcing its role in integrated pest management (IPM).

Security profile

One of ledprone's greatest attractions is its exceptional safety profile, aligned with regenerative agriculture. It is highly selective, with no detectable effects on non-target arthropods such as ladybugs (beneficial predators), pollinators, birds, fish, or humans—classified as Category IV toxicity by the EPA (low oral toxicity).

A 2025 study analyzed responses of non-target arthropods in Calantha-treated fields and found no impacts on abundance or diversity of beneficial species.

Environmentally, the molecule degrades rapidly: a half-life of less than 1 hour under aerobic and aquatic conditions, no persistence in soil or water, and no detectable residues in potato crops. This contrasts with persistent chemical insecticides, reducing contamination risks and promoting biodiversity.

Despite initial criticism from groups like the Center for Food Safety about ecological assessments, the EPA confirmed in 2023-2024 that the risks are negligible, with exemptions from residue tolerances.