RNAi biopesticides

01Overview and value chain

Markers: [EC: Farm to Fork & Sustainable Use Regulation | OECD: Agricultural Biotechnology | Regulator: EPA (USA), EFSA (EU), MoA (China)]

RNAi biopesticides exploit RNA interference: a topically applied double-stranded RNA (dsRNA) matching an essential pest gene is taken up by the insect, processed into small interfering RNAs, and silences that gene, killing the pest with high species specificity. The first sprayable dsRNA insecticide reached the market only at the end of 2023, yet within roughly two years the category spans 5 milestone products across insecticide, miticide and fungicide use. Unlike transgenic plant-incorporated RNAi, sprayable dsRNA leaves no genetic modification in the crop and degrades in days to weeks, which underpins its favorable environmental profile. The central challenges are dsRNA cost, environmental stability and delivery.

Key directions of RNAi biopesticides are:

1. Sprayable dsRNA insecticides (Sprayable dsRNA Insecticides): foliar dsRNA targeting chewing pests such as the Colorado potato beetle, now EPA-registered.
2. dsRNA miticides and fungicides (dsRNA Miticides & Fungicides): the first RNA varroa-mite treatment is registered, and RNAi fungicides have advanced toward US, EU and Brazil submissions.
3. Nanoparticle-protected delivery (Nanoparticle-Protected Delivery): lipid and clay nanocarriers protect dsRNA against degradation and improve cellular uptake.
4. Computational target design (Computational Target Design): AI/bioinformatic platforms select pest-specific, off-target-safe gene sequences before synthesis.

Sectoral value chain

[target design] ──> [dsRNA synthesis] ──> [formulation] ──> [field spray]
                                  │
                          (gene silencing)
                                  │
                                  ▼
[pest mortality] <─── [insect uptake] <─────┘

Value chain levels

Cross-cutting technologies of the sector:

• Cell-free dsRNA synthesis (Cell-Free dsRNA Synthesis): enzymatic production decoupling cost from fermentation scale.
• Nanoparticle delivery (Nanoparticle Delivery): lipid/clay carriers extending field half-life.
• dsRNA design platforms (dsRNA Design Platforms): software such as dsRNAEngineer for target selection.

02US

The US leads on regulatory firsts: the first sprayable dsRNA insecticide and the first RNA bee-mite treatment were both registered here.

first sprayable approval, non-target safety, cell-free production

• EPA registration of Calantha: ledprona, the first sprayable dsRNA insecticide, registered for the Colorado potato beetle in December 2023; it silences the pest’s PSMB5 proteasome-subunit gene, halting larval feeding.
• Non-target arthropod review: published field studies assess effects of dsRNA bioinsecticides on non-target arthropods, underpinning the EPA biopesticide review track.
• Cell-free dsRNA manufacturing: US platforms scale T7-polymerase-driven cell-free enzymatic synthesis of dsRNA, collapsing the per-gram cost ceiling that had kept the field academic.

03CN

China couples strong academic RNAi research with fast-growing domestic interest in dsRNA crop protection.

design platforms, target screening, fermentation scale-up, market forecasts

• dsRNAEngineer platform: Southwest University (Wang Jinjun lab) published an intelligent dsRNA design tool in Trends in Biotechnology.
• Key-gene RNAi for orchard pests: national R&D sub-projects screen and silence pest genes for fruit-tree protection.
• Academic SIGS targets: the CAS State Key Lab of Plant Genomics (Institute of Genetics and Developmental Biology, Beijing) maps essential-gene silencing targets in fungal pathogens such as the wheat scab pathogen Fusarium.
• Low-cost fermentation scale-up: Chinese groups produce bulk dsRNA through microbial fermentation in RNase-III-deficient Escherichia coli HT115 strains, the low-cost route most Asian programmes rely on.
• Domestic market outlook: Chinese industry reports forecast rapid growth of the RNAi-pesticide market to 2031.

04EU

The EU emphasizes biocontrol policy and rigorous environmental risk assessment of RNA-based products.

biocontrol policy, EFSA risk assessment, nano-formulation research

• Farm to Fork biocontrol push: the EU Farm to Fork strategy targets a 50% cut in chemical pesticide use by 2030, framing species-specific RNAi biocontrol as a key substitute.
• EFSA environmental risk assessment: dedicated frameworks evaluate environmental fate and non-target effects of dsRNA, requiring applicants to screen the sequence against non-target genomes to exclude homology stretches that could drive off-target silencing.
• Nano-enabled RNAi research: EU groups advance nanoparticle delivery for lepidopteran-pest management.

05Leading companies and research institutes

06Tech stack and innovations

The stack combines low-cost dsRNA production, protective delivery and computational design.

1. Cell-free dsRNA synthesis (Cell-Free dsRNA Synthesis):
   • T7-RNA-polymerase-driven enzymatic in-vitro transcription decouples output from fermentation capacity.
   • drives down cost per gram, the main barrier to field-scale RNAi.
2. Nanoparticle delivery (Nanoparticle Delivery):
   • the BioClay platform — layered double hydroxide (LDH, Mg/Al) nanoclay developed at the University of Queensland — electrostatically binds dsRNA, shielding it from nucleases and UV.
   • lipid and clay nanocarriers improve cuticular and gut uptake to extend field efficacy.
3. Computational target design (Computational Target Design):
   • platforms such as dsRNAEngineer pick essential, species-specific genes.
   • multi-target stacking — dsRNAs aimed at several essential genes at once — lowers resistance risk; sequences are screened against non-target genomes to limit off-target effects.

07Value chains and production pipelines

Industrial pipeline of a sprayable dsRNA product (EPA FIFRA registration)

┌───────────────────────────┐      ┌───────────────────────────┐
│ 1. Target gene discovery  │ ───> │ 2. dsRNA sequence design  │
└───────────────────────────┘      └───────────────────────────┘
                                                 │
                                                 ▼
┌───────────────────────────┐      ┌───────────────────────────┐
│ 4. Formulation & delivery │ <─── │ 3. dsRNA production        │
└───────────────────────────┘      └───────────────────────────┘
              │
              ▼
┌───────────────────────────┐      ┌───────────────────────────┐
│ 5. Regulatory & safety    │ ───> │ 6. Field application       │
└───────────────────────────┘      └───────────────────────────┘

Stage 1: Target gene discovery

Pest genomes and functional screens identify essential genes whose silencing is lethal to the target insect.

Stage 2: dsRNA sequence design

Bioinformatic platforms design a dsRNA matching the target gene while screening against non-target species to limit off-target effects.

Stage 3: dsRNA production

Cell-free enzymatic synthesis or fermentation produces bulk dsRNA, where cost per gram is the key economic constraint.

Stage 4: Formulation and delivery

dsRNA is combined with nanoparticle carriers and adjuvants to resist degradation and improve uptake into the pest.

Stage 5: Regulatory and safety review

Agencies assess environmental fate and non-target arthropod safety; EPA registered the first such product (Calantha) in December 2023.

Stage 6: Field application

The formulated product is sprayed on the crop, taken up by feeding insects, and silences the target gene to suppress the pest population.