Fraunhofer Institute for Molecular Biology and Applied Ecology IME
A new era in plant protection: how the first RNAi spray on the market works against Colorado potato beetles
Climate change and intensive agriculture are promoting the spread of insect pests. At the same time, conventional insecticides are coming under pressure due to environmental and health risks and increasing resistance. With Calantha® (active ingredient: ledprona), GreenLight Biosciences has obtained approval in the USA in 2023 for the world's first RNAi spray. A recent study by GreenLight Biosciences, the Fraunhofer Institute for Molecular Biology and Applied Ecology IME (Bioresources Division) and Justus Liebig University Giessen explains the mechanism of action. The spray specifically switches off a vital gene in the Colorado potato beetle and also triggers a previously undescribed secondary effect, which leads to a lethal accumulation of proteins in the insect's body. The study demonstrates the specificity of the dsRNA and identifies the subsequent proteasome malfunction caused by the downregulation as the mechanism of action of ledprona.
An overview of the most important facts:
- Technology: RNA interference (RNAi) uses double-stranded RNA (dsRNA) to specifically inhibit the formation of selected proteins in insect pests. Andrew Fire and Craig Mello were awarded the Nobel Prize in Physiology and Medicine in 2006 for their discovery of this mechanism.
- Product: Calantha® (ledprona) is a dsRNA spray that was recently approved in the USA and is effective against Colorado potato beetle larvae (Leptinotarsa decemlineata), a globally significant pest in potato cultivation.
- Mode of action: The dsRNA targets the gene for the proteasome subunit beta-type 5 (PSMB5). Its inhibition disrupts the assembly of the cellular protein recycling system (26S proteasome), resulting in an accumulation of damaged proteins, which ultimately kills the larvae.
- Specificity and environment: The dsRNA is designed so that its sequence specifically targets only the target insect organism; additional advantages are that the dsRNA is biodegradable and leaves no toxic pesticide residues.
This is how RNAi works in the field:
RNAi sprays are applied to crops in a similar way to conventional pesticides. When a pest insect feeds on the treated leaves, it ingests the dsRNA. This specifically switches off the activity of previously selected genes in the insect's cells that are essential for survival. Ledprona inhibits the synthesis of the catalytic proteasome subunit PSMB5 in the Colorado potato beetle. This prevents the correct proteasome assembly and the cell's own protein recycling, which is a key reason for the death of the larvae. The GreenLight Biosciences platform enables the cost-effective biochemical production of dsRNA without the use of genetically modified organisms. GreenLight Biosciences has submitted further RNAi sprays for approval, including one against the Varroa mite.
Looking toward Europe and next steps:
In Germany and other EU countries, field studies with Calantha® confirm its effectiveness against the Colorado potato beetle larvae. However, for farmers to benefit from such highly targeted, environmentally friendly options, an appropriate regulatory approval pathway for RNAi sprays is needed in the EU. At the Bioresources branch of the Fraunhofer IME, RNA sprays against aphids as well as against the reed glass-winged planthopper (Pentastiridius leporinus), a new major pest in sugar beet cultivation, are currently being developed. This work is partially funded by the EU Horizon project NextGenBioPest. A key factor in effective RNAi in these species is the formulation, which must be tailored to each pest, and must also be biologically degradable and non-toxic.
Publication:
Graser L, Gordon ER, Jamison M, Talton W, Chen Y, Knorr E, Windfelder A, Narva K & Vilcinskas A.
Targeting the proteasome subunit PSMB5 by RNA interference induces proteasome dysfunction and mortality in the Colorado potato beetle (Leptinotarsa decemlineata).
Sci Rep 15, 41183 (2025). https://www.nature.com/articles/s41598-025-28793-x
More information:
