Sprayable RNA biopesticides

In plain language

Many insects, plants and animals already use a natural process called RNA interference to control which genes are active. Scientists can design a short piece of double-stranded RNA that matches a gene in a pest, so that when the pest takes it in, the matching gene message is broken down and the protein it makes is not produced. Unlike a genetically modified crop, the change is not carried in the plant's own genome. The RNA is simply applied to the leaves like a spray.

The approach is attractive because it can, in principle, be aimed at one pest species using a gene that other animals do not share. The US Environmental Protection Agency (EPA) registered Ledprona in December 2023 as a spray against Colorado potato beetle, which it says works by silencing a beetle gene needed to make a protein called PSMB5. The main open questions are practical ones: how long the RNA stays active on leaves, how cheaply it can be made in large amounts, and whether pests will evolve resistance to it.

Technical explanation

A dsRNA biopesticide is a synthetic double-stranded RNA molecule whose sequence matches a target gene in the pest. After ingestion or uptake, the pest's RNA interference machinery processes the dsRNA into short fragments that guide the degradation of matching messenger RNA. Sprayed products avoid the transgene route, which Kadoić Balaško and colleagues (2020) say has faced public acceptance problems, especially in the EU. Sprayed dsRNA, however, sits on the leaf surface, and the same review lists dsRNA degradation and the lack of practical delivery methods as obstacles. Hough and colleagues (2022) state that commercial dsRNA biocontrols need economical large-scale production and suitable delivery methods.

The registered product Ledprona was reviewed by EPA under the Federal Insecticide, Fungicide, and Rodenticide Act. EPA's public materials describe an experimental use permit in May 2023 covering testing in ten states, a proposal released on 29 September 2023 with a comment period that EPA describes as 15 days, and a three-year registration announced on 22 December 2023. The EPA announcement does not describe the active ingredient's environmental degradation, persistence or efficacy trial data, so those details must be checked in the docket and decision documents. The company, GreenLight Biosciences, states that the product degrades within three days and does not affect tested non-target species at 100 times the field rate. These statements are company claims and were not checked against independent field data for this profile.

Resistance is a separate issue. Kadoić Balaško and colleagues (2020) list the evolution of resistance to RNAi among the factors that have limited its practical use, and they describe spray-induced gene silencing as a more realistic option than transgenic plants for Colorado potato beetle. Because a single-gene target may give a pest a route to resistance, the pest's population genetics and the rotation of modes of action matter. EPA states that the product aids resistance management, but the announcement lists no required resistance-management measures for growers.

What the evidence says

Each statement is typed by the strength of its evidence and linked to the source that supports it.

Limitations and open problems

• The EPA registration announcement does not report field efficacy data, environmental persistence or degradation rates for Ledprona, so the strongest persistence claims in the public record come from the manufacturer.
• Production cost per gram of dsRNA at commercial scale is not stated in this profile. Hough and colleagues (2022) give earlier production cost estimates in their Discussion, which are not commercial prices for Ledprona.
• Resistance risk is largely untested in the field. Kadoić Balaško and colleagues (2020) name resistance to RNAi as a challenge, and the EPA registration lists no required resistance-management measures for users.
• Non-target safety rests heavily on the manufacturer's own testing. EPA reports no risk of concern to human health and the environment and no effects on listed species under the Endangered Species Act, but the announcement does not describe other non-target organism testing.
• The registration covers one pest on potato crops for three years, so it does not show that the approach works across other pests, crops or climates.
• The sources reviewed for this profile were a mix of government announcements, one company press release and two review articles. Peer-reviewed field trial papers on Ledprona were not opened, so efficacy claims are limited to what the review articles and regulator state.

Possible future uses

Timeline

1. 1 Sept 2020Kadoić Balaško and colleagues publish a review of Colorado potato beetle control and resistance management, arguing that spray-induced gene silencing is a more realistic option than transgenic plants. Sources: [5]
2. 10 Oct 2022Hough and colleagues publish a review of dsRNA biocontrol production, stating that commercialisation requires economical production of large quantities of dsRNA and suitable delivery methods. Sources: [4]
3. May 2023EPA approves an experimental use permit for Ledprona under FIFRA, for testing in 10 states. Sources: [1]
4. 29 Sept 2023EPA releases its proposal to register Ledprona for potato crops and opens a public comment period that EPA describes as 15 days, closing 13 October 2023. Sources: [1]
5. 22 Dec 2023EPA registers Ledprona-based biopesticides for three years for use against Colorado potato beetle. Sources: [2]
6. 4 Jan 2024GreenLight Biosciences announces the registration of Calantha, stating that it degrades within three days, a company claim not independently verified in this profile. Sources: [3]

Futures this could help bring about

How far away?

Farming with far fewer chemical pesticides

Pilots · 4 of 8 steps done

Glossary

dsRNA

Double-stranded RNA, a two-stranded form of RNA that cells use to switch off matching genes.

RNA interference (RNAi)

A natural process in which double-stranded RNA guides the breakdown of messenger RNA that matches it, reducing the protein made from that gene.

Ledprona

The active ingredient in Calantha, a sprayable dsRNA that EPA registered to silence a Colorado potato beetle gene.

Experimental use permit (EUP)

A limited permit under US pesticide law that allows a product to be tested in the field before full registration.

Sources

1. government report
   EPA Opens Public Comment Period on Proposal to Register Novel Pesticide Technology for Potato Crops
   US Environmental Protection Agency, 29 Sept 2023. Accessed 21 Oct 2026.
2. government report
   EPA Registers Novel Pesticide Technology for Potato Crops
   US Environmental Protection Agency, 22 Dec 2023. Accessed 21 Oct 2026.
3. company announcement
   GreenLight Biosciences Secures EPA Registration for New Bioinsecticide, Calantha, Historic Step Towards A Safer and More Sustainable Food System
   PR Newswire (reposted on BioSpace), 4 Jan 2024. Accessed 21 Oct 2026.
4. review article
   Strategies for the production of dsRNA biocontrols as alternatives to chemical pesticides
   J. Hough, J.D. Howard, S. Brown et al.. Frontiers in Bioengineering and Biotechnology, 10 Oct 2022. DOI: 10.3389/fbioe.2022.980592. Accessed 21 Oct 2026.
5. review article
   Modern Techniques in Colorado Potato Beetle (Leptinotarsa decemlineata Say) Control and Resistance Management: History Review and Future Perspectives
   Martina Kadoić Balaško, Katarina M. Mikac, Renata Bažok et al.. Insects (MDPI), 1 Sept 2020. DOI: 10.3390/insects11090581. Accessed 21 Oct 2026.

Revision history

3 changes since this profile was created.