An RNAi-based drug to combat varroasis?

© TOMASZ KLEJDYSZ

► Read for you

RNA interference offers a new approach to varroa control: instead of killing the mite directly, it aims to block the expression of an essential parasite gene. This article summarizes what is currently known about vadescana/Norroa, early laboratory and field trials, and the remaining questions for honey bees, non-target organisms, and beekeeping in Switzerland.

1. Key points

• RNA interference (RNAi) makes it possible to reduce the expression of a gene by blocking the corresponding messenger RNA, without modifying DNA.
• In the bee, ingested double-stranded RNAs can circulate within the colony, which makes the technique interesting against varroa but also justifies a cautious evaluation.
• Vadescana, registered in the United States under the name Norroa, targets a calmodulin gene of Varroa destructor and reduces primarily the reproduction of the foundress mites.
• The available data show a real but variable effect: strong in mini-hives, more partial in production apiaries and dependent on the colony context.
• For Swiss apiaries, RNAi should be presented as a technology to watch, not as a practical recommendation: to our knowledge, no veterinary medicine based on vadescana or Norroa is currently authorised in Switzerland.

The discovery of this mechanism, known as RNA interference, earned the two researchers the Nobel Prize in Physiology or Medicine in 2006. The same Nobel Prize in Medicine has just been awarded in 2024 to Victor Ambros and Gary Ruvkun for discovering microRNAs — small interfering RNAs that occur naturally in all living organisms and play a fundamental role in regulating gene expression. These microRNAs are part of the mechanisms that explain, for example,
why not all cells in our body are identical, even though they all start out with the same genetic material. These are major discoveries, both for the field they open up in our understanding of natural processes and for their potential applications.

2. What the study shows

This chapter summarises the article by Janine Kievits, which presents the principle of RNAi, its potential interest against varroosis, and the safety questions it raises. Fig. 2: This image illustrates the process of RNA interference (RNAi), a natural biological mechanism used by cells to regulate gene expression, often referred to as gene silencing. (Source: Wikipedia)

Question. The article raises a central question: can a medicine based on interfering RNA become a new tool against varroosis, and under what conditions can it be considered effective, targeted and safe? The issue is not only technical. It also concerns how an innovation arising from molecular biology can be evaluated before being offered to beekeepers.

Method. The article is a critical synthesis. It first recalls the basics of gene expression: DNA contains the information, messenger RNA carries a working copy of it, and the cell then produces the corresponding protein. Interfering RNA acts at this intermediate step: it binds to a targeted messenger RNA and prevents protein production. The article then traces the applications envisaged in bees, from trials against viruses or Nosema to more recent work targeting Varroa destructor (Kievits, 2025).

Results. The article first presents the bee as a special case. Ingested double-stranded RNAs can pass into the haemolymph, be found in brood food secretions and be redistributed within the colony. This circulation can become a therapeutic advantage: bees fed with a syrup containing the targeted RNA can pass the molecule on to the brood and to varroa, particularly when the mite feeds on the bee or inside the brood cell.

The article then describes a first study against varroosis, in which bees fed with RNAs targeting genes of Varroa destructor pass these RNAs on to the mite. The expression of certain targeted genes is reduced and the varroa population decreases in mini-colonies (Garbian et al., 2012, cited by Kievits, 2025).

The most concrete case is vadescana, developed by GreenLight Biosciences. It is a double-stranded RNA designed to target a calmodulin gene in Varroa destructor. In the study by McGruddy et al. (2024), as summarised by Kievits, mini-hives received a syrup containing vadescana at two concentrations. The product did not significantly reduce mite survival, but it strongly reduced their reproduction: 71% of foundresses in the control group produced offspring, compared with 6% and 9% in the two treated groups.

Kievits's article also mentions an Italian field study published by Bortolin et al. (2025). This time the product is not vadescana but a mixture of three double-stranded RNAs targeting other genes of Varroa destructor. The trial involves hives under real beekeeping conditions in Veneto. Treated colonies show a smaller increase in phoretic infestation than control colonies.

Interpretation. The article presents RNAi as a promising technology but not as a solution already stabilised for beekeeping practice. Its appeal is clear: it targets a precise biological mechanism of the parasite, with a mode of action different from classical acaricides. Its limit is just as important: perfect specificity is not guaranteed, off-target effects are documented in the literature, and the available trials remain too limited to conclude on robust safety and efficacy in all apiary contexts.

3. Critical perspective

The scientific interest is real, but transposing this to the apiary must remain cautious: the data are still recent, partial and dependent on the experimental context.

The article's main strength is that it does not reduce RNAi to a technological promise. It explains the mechanism, shows why the bee is a particularly interesting model and places vadescana within a longer history of research on double-stranded RNAs in bees. It also avoids two common shortcuts: equating RNAi with a genetic modification of the bee, or presenting a targeted molecule as automatically free of risk.

The available studies support the idea that RNAi can disrupt varroa. But the levels of evidence are not the same. McGruddy et al. (2024) show a strong effect on foundress reproduction, but in mini-hives. Bortolin et al. (2025) provide evidence closer to field conditions, but the effect measured concerns the change in phoretic infestation over a short period, not the entire reproductive cycle of varroa within the brood.

This caution is reinforced by the size of the trials. In the Italian study, 50 colonies were planned, but only 37 were included in the final analysis after exclusions related notably to external events. The authors themselves note that the protocol, designed with the beekeepers and adapted to production constraints, did not allow direct measurement of mites in brood cells (Bortolin et al., 2025). This is a strength for feasibility in the apiary, but a limit for fine biological interpretation.

Another critical point concerns off-target effects. Earlier work in bees shows that supposedly neutral double-stranded RNAs can alter the expression of numerous genes or produce tissue- and dose-dependent effects (Jarosch & Moritz, 2012; Nunes et al., 2013). This does not mean that vadescana will necessarily have such effects under conditions of use, but it does rule out hasty conclusions about general safety.

The question of economic interests must also remain visible. In the study by McGruddy et al. (2024), some authors are affiliated with GreenLight Biosciences, the developer of vadescana, and the study received support from this company. This link does not disqualify the results, but it justifies waiting for independent confirmation. By contrast, the study by Bortolin et al. (2025) declares no conflict of interest and was funded by the Rural Development Programme of the Veneto Region.

An important merit of Kievits's article is to remind us that the question is not only technical. RNAi is a powerful tool at the interface of animal health, biotechnology and markets. For a medicine intended for bees, evaluation should therefore remain demanding, independent and long enough to detect any rare, sublethal or delayed effects at the colony level.

What cannot be concluded at this stage is essential for ApiSavoir: it cannot be said that RNAi replaces proven anti-varroa strategies; it cannot be claimed that the risk is nil; and one cannot directly extrapolate from mini-hives, from a short Italian trial or from North American trials to Swiss conditions, with their variations in altitude, nectar flows, brood management and treatment schedules.

Fig. 3: Top: the complete life cycle of an Apis mellifera worker bee, from egg to adult (21 days), with the reproductive cycle of Varroa destructor during the bee's pupation period highlighted by a rectangle whose arrow points to the image below.

Bottom: a detailed overview of the typical reproductive cycle of Varroa inside the capped cell of a worker bee, over a 12-day pupation period. The foundress mite enters the bee's larval cell one or two days before the cell is capped and the 12-day pupation period of the worker bee begins. The foundress lays her first egg about 3 days after the cell is capped and continues to lay one egg roughly every 30 hours until she has laid 5 to 6. The first egg to hatch is a male, easily identifiable because it is much smaller and rounder than the females. The male waits for the females to hatch and reach maturity before mating with them. By the time the mature worker bee emerges on day 12, one or two daughters will have reached maturity and will leave the newly emerged bee together with the foundress. The male and the remaining immature females die. We introduced vadescana into mini-hives about 3 days before the start of the pupation period, when the developing bees were third-instar larvae. The nurse bees provisioned the cells with vadescana before capping them, the point at which the mites would also have crawled into the cell. We uncapped and examined mites and bees around day 11 or 12. (Source: McGruddy et al., 2024)

4. What related studies show

Related studies confirm a real potential, but they also show that efficacy depends on the targeted gene, the route of administration, the stage of the parasite and the colony context. Fig. 4: Variation in the level of phoretic varroa infestation (post/pre-treatment ratio) between days 1 and 37 of the trial for the three treatments. (Source: Bortolin F. et al. (2025))

Direct precursor. Garbian et al. (2012) demonstrated bidirectional transfer between the bee and Varroa destructor: bees fed with RNA targeting varroa pass it on to the mites, and the mites can in turn transfer RNA to the parasitised bee. This study is a direct precursor to the principle discussed here, but it does not yet correspond to the conditions of a production apiary.

Mechanistic support. The work of Maori et al. (2019a, 2019b) is important for understanding why the bee is a special case. They describe a pathway for RNA transfer via haemolymph, royal jelly and exchanges between individuals, with a stabilising role for the MRJP-3 protein. This mechanism explains why a product administered through feeding can reach the brood and reproducing varroa, but it also stresses that exposure does not concern only the adults that consume the syrup.

Efficacy against varroa. McGruddy et al. (2024) provide the most targeted demonstration for vadescana. The product is administered in syrup pouches placed in mini-hives with nurse bees, brood and varroa. The observed effect on reproduction is very clear: foundresses exposed to vadescana produce far fewer offspring than those in the control groups. By contrast, foundress survival is not significantly reduced. The mode of action therefore appears to be mainly anti-reproductive, at least in this setup.

The study by Bortolin et al. (2025) is important because it shifts the question towards the field. The researchers used a mixture of three double-stranded RNAs targeting acetyl-CoA carboxylase, Na+/K+ ATPase and an endochitinase of Varroa destructor. In the laboratory, silencing was significant for two of the three targets tested: acetyl-CoA carboxylase and Na+/K+ ATPase. It was not significant for the endochitinase, a reminder that the choice of target remains decisive. In the apiary, the treated colonies received seven administrations of syrup containing the double-stranded RNAs, one every three days. Between day 1 and day 37, the increase in phoretic infestation was reduced by 33% compared with the syrup control and by 42% compared with the GFP-dsRNA control. No significant effect was detected on adult bee survival or on colony strength in brood or adult bees.

The results conveyed by Consensus also point to additional trials. Muntaabski et al. (2022) show that bacterially produced double-stranded RNA administered orally to bees can reduce target gene expression in varroa and decrease its survival. Muntaabski et al. (2025) explore several genes involved in the reproductive success of the parasite and confirm that the choice of target is decisive. These studies support the mechanism but do not yet constitute practical validation comparable with already established anti-varroa treatments.

Field data subsequent to Kievits's article. A field study published in 2026 tests Norroa in Florida during a nectar flow and a dearth period. During the flow, treated colonies keep varroa levels at or below the initial level for twelve weeks, whereas control colonies increase more. During the dearth, treated colonies increase less than the controls, but the difference is not significant. Varroa from treated colonies are also less likely to lay or produce viable offspring (Rawn et al., 2026). This study is useful, but it is not an independent replication in the strict sense: several authors are affiliated with GreenLight Biosciences or the University of Florida, and the study must be read with this context in mind.

Another study published in 2026 compares colonies treated with vadescana, colonies treated with amitraz and untreated colonies, with monitoring of longevity and foraging behaviour by RFID. Under the trial conditions, bees from untreated colonies live less long; those from vadescana-treated colonies occupy an intermediate position, while those from amitraz-treated colonies show the longest longevity. The study also reports an increase in foraging activity in the vadescana group (Merk et al., 2026). This result can be read as a sign of improved health status through reduced varroa pressure, but also warrants caution, because increased foraging activity can sometimes accompany sublethal changes in behaviour. The study was funded in part by GreenLight Biosciences and includes authors affiliated with the company.

Off-target effects in the bee. Studies on off-target effects call for a balanced reading. On one hand, trials targeting varroa do not report major negative effects on bee survival under the conditions studied (McGruddy et al., 2024; Bortolin et al., 2025). On the other hand, methodological studies in bees show that some double-stranded RNAs can produce non-specific effects on gene expression or development, particularly depending on dose, sequence, route of administration and developmental stage (Jarosch & Moritz, 2012; Nunes et al., 2013).

Non-target organisms. The results conveyed by Consensus suggest a rather reassuring but still incomplete picture. Krishnan et al. (2021) do not report any concerning effect of a varroa-active dsRNA on monarch butterfly larvae under the conditions tested. Bulgarella et al. (2025) report an in silico analysis of off-target risks for a next-generation double-stranded RNA acaricide against varroa, together with trials on a bee-associated arthropod, without any signal of a major effect under the conditions studied. These works are useful, but they do not cover the full diversity of wild pollinators or all plausible exposure pathways in the apiary.

Place in integrated pest management. Reviews on the control of Varroa destructor do not yet place RNAi on the same footing as organic acids, thymol, biotechnical methods or selection strategies. They present it rather as an emerging, potentially complementary avenue, which will need to be evaluated in terms of efficacy, cost, possible resistance, off-target effects and beekeeping feasibility (Christiaens et al., 2021; Jack & Ellis, 2021; Noël et al., 2020).

5. What does this mean for the apiary?

For the Swiss beekeeper, the immediate value lies above all in understanding the technology and its limits, not in changing the current control plan.

Regulatory status and availability. In the United States, the EPA finalised the registration of vadescana and two Norroa formulations against Varroa destructor in September 2025. The agency also established a permanent exemption from tolerance for vadescana residues in honey and comb when the product is used according to the label and good practices.

In the European Union, document EMA/CVMP/EWP/459883/2008 Rev.1 remains the adopted guideline for the evaluation of veterinary medicines against varroosis. A Rev.2 revision is in public consultation from 23.01.2026 to 31.05.2026; it explicitly mentions new modes of action, including RNAi, but it is a draft guideline, not yet an adopted text.

In Switzerland, Norroa or vadescana must not be presented as available at the apiary as long as they do not appear in the relevant official sources. To our knowledge, they do not appear in the current list of Swissmedic-authorised veterinary medicines. Before publication or any later update, this point should be re-verified directly in the Swissmedic lists, the Veterinary Medicines Compendium and, where applicable, FSVO or cantonal implementation information.

Conditions of use. The US information describes Norroa as a syrup pouch containing vadescana, intended to be consumed by the bees and transferred to the brood nest. The points to retain are mainly biological: the presence of open brood is important, the expected effect concerns primarily varroa reproduction, and efficacy appears less suited to situations where infestation is already very high. The precise conditions of use with or without supers, the application periods, the number of applications and any withdrawal periods must not be transposed to Switzerland without local authorisation and a Swiss label.

• RNAi against varroa deserves attention but does not, today, replace the Swiss framework for the control of varroosis. As long as a product is not authorised and integrated into the official recommendations, the practical reference remains Practical Guide 1.1: Varroa management concept, with infestation monitoring, authorised treatments and well-timed interventions.
• If an RNAi medicine becomes available in Switzerland one day, it will probably need to be judged differently from a shock treatment. The available data point above all to an effect on varroa reproduction, that is, an ability to slow the increase in infestation rather than to cause a massive and immediate drop in mites.
• The term "targeted" must be understood with caution. A well-designed sequence may reduce the risk to the bee and to non-target organisms, but it is not enough to prove the absence of sublethal effects on brood, nurse bees, the queen, behaviour or overwintering.
• For a Swiss or temperate European apiary, the decisive question will be the treatment schedule. A technology that acts on varroa reproduction will need to be evaluated in relation to brood dynamics, the production of winter bees, local nectar flows and treatment thresholds — not solely on an average efficacy measured in a trial.
• Before any future adoption, it will be necessary to verify the authorisation status, the conditions of use, the restrictions related to honey, any withdrawal periods, the number of applications, independent data and possible interactions with other control methods. Without these elements, RNAi remains a promising lead, not a beekeeping directive.

Read the original article

Kievits, J. (2025). Un médicament à base d'ARNi pour lutter contre la varroose? La Santé de l'Abeille, No. 328, July–August 2025.

See also:

• Practical Guide 1.1: Varroa management concept
• From the varroa cycle to assessment methods
• Practical Guide: Recommended beekeeping preparations
• Practical Guide 1.6.6: Infestation-based varroa treatment
• The colony facing varroa: resistance, resilience and the limits of selection
• Medicines / preparations authorised in Switzerland
• The bee genome


•  

Bibliography

Bortolin, F., Rigato, E., Perandin, S., Granato, A., Zulian, L., Millino, C., Pacchioni, B., Mutinelli, F., & Fusco, G. (2025). First evidence of the effectiveness of a field application of RNAi technology in reducing infestation of the mite Varroa destructor in the western honey bee (Apis mellifera). Parasites & Vectors, 18, 28. https://doi.org/10.1186/s13071-025-06673-7

Bulgarella, M., Reason, A., Baty, J., McGruddy, R., Gordon, E., Devisetty, U., & Lester, P. (2025). In silico analysis of potential off-target effects of a next-generation dsRNA acaricide for varroa mites (Varroa destructor) and lack of effect on a bee-associated arthropod. Insects, 16. https://doi.org/10.3390/insects16030317

Chen, J., Peng, Y., Zhang, H., Wang, K., Zhao, C., Zhu, G., Palli, S., & Han, Z. (2021). Off-target effects of RNAi correlate with the mismatch rate between dsRNA and non-target mRNA. RNA Biology, 18, 1747–1759. https://doi.org/10.1080/15476286.2020.1868680

Christiaens, O., Sweet, J., Dzhambazova, T., Urru, I., Smagghe, G., Kostov, K., & Arpaia, S. (2021). Implementation of RNAi-based arthropod pest control: Environmental risks, potential for resistance and regulatory considerations. Journal of Pest Science, 95, 1–15. https://doi.org/10.1007/s10340-021-01439-3

European Medicines Agency. (2021). Guideline on veterinary medicinal products controlling Varroa destructor parasitosis in bees. EMA/CVMP/EWP/459883/2008-Rev.1. Legal effective date: 28.01.2022.

European Medicines Agency. (2026). Draft guideline on veterinary medicinal products controlling Varroa destructor parasitosis in bees — Revision 2. EMA/CVMP/EWP/459883/2008-Rev.2. Draft: consultation open 23.01.2026–31.05.2026.

Garbian, Y., Maori, E., Kalev, H., Shafir, S., & Sela, I. (2012). Bidirectional transfer of RNAi between honey bee and Varroa destructor: Varroa gene silencing reduces varroa population. PLoS Pathogens, 8. https://doi.org/10.1371/journal.ppat.1003035

Jack, C., & Ellis, J. (2021). Integrated pest management control of Varroa destructor, the most damaging pest of Apis mellifera colonies. Journal of Insect Science, 21. https://doi.org/10.1093/jisesa/ieab058

Jarosch, A., & Moritz, R. F. A. (2012). RNA interference in honeybees: Off-target effects caused by dsRNA. Apidologie, 43, 128–138. https://doi.org/10.1007/s13592-011-0092-y

Krishnan, N., Hall, M. J., Hellmich, R. L., Coats, J. R., & Bradbury, S. P. (2021). Evaluating toxicity of Varroa destructor-active dsRNA to monarch butterfly (Danaus plexippus) larvae. PLoS ONE, 16. https://doi.org/10.1371/journal.pone.0251884

Maori, E., Garbian, Y., Kunik, V., Mozes-Koch, R., Malka, O., Kalev, H., Sabath, N., Sela, I., & Shafir, S. (2019a). A transmissible RNA pathway in honey bees. Cell Reports, 27, 1949–1959.

Maori, E., Navarro, I. C., Boncristiani, H., Seilly, D. J., Rudolph, K. L. M., Sapetschnig, A., et al. (2019b). A secreted RNA binding protein forms RNA-stabilizing granules in the honeybee royal jelly. Molecular Cell, 74, 598–608.

McGruddy, R. A., Smeele, Z. E., Manley, B., Masucci, J. D., Haywood, J., & Lester, P. J. (2024). RNA interference as a next-generation control method for suppressing Varroa destructor reproduction in honey bee (Apis mellifera) hives. Pest Management Science, 80, 4770–4778. https://doi.org/10.1002/ps.8193

Merk, J., Anastasi, M., McGruddy, R., Manley, B., Felden, A., & Lester, P. J. (2026). Longevity and foraging performance of honey bees treated with an RNAi-based Varroa destructor biopesticide. Scientific Reports, 16, 8208. https://doi.org/10.1038/s41598-026-38557-w

Muntaabski, I., Scannapieco, A., Liendo, M., Niz, J., Russo, R., & Salvador, R. (2022). Bacterially expressed dsRNA induces Varroa destructor gene knockdown by honey bee-mediated oral administration. Journal of Apicultural Research, 61, 511–518. https://doi.org/10.1080/00218839.2022.2028967

Muntaabski, I., Salvador, R., Russo, R., Wulff, J., Landi, L., Liendo, M., Lanzavecchia, S., & Scannapieco, A. (2025). Assessing the role of key genes involved in the reproductive success of the honey bee parasite Varroa destructor. BMC Genomics, 26. https://doi.org/10.1186/s12864-025-11805-5

Noël, A., Le Conte, Y., & Mondet, F. (2020). Varroa destructor: How does it harm Apis mellifera honey bees and what can be done about it? Emerging Topics in Life Sciences, 4, 45–57. https://doi.org/10.1042/ETLS20190125

Nunes, F. M. F., Aleixo, A. C., Barchuk, A. R., Bomtorin, A. D., Grozinger, C. M., & Simões, Z. L. P. (2013). Non-target effects of green fluorescent protein-derived double-stranded RNA used in honey bee RNA interference assays. Insects, 4, 90–103. https://doi.org/10.3390/insects4010090

Rawn, D. R., Prouty, C., Gautam, A. G., Jamison, M., Talton, W., Youngs, K., Narva, K., Manley, B., & Jack, C. J. (2026). Evaluating the new product Norroa™ against Varroa destructor in managed honey bee (Apis mellifera) colonies. Frontiers in Insect Science, 6, 1751606. https://doi.org/10.3389/finsc.2026.1751606

Swissmedic. (2026). Lists and tables — Authorised veterinary medicines. Lists available at www.swissmedic.ch.

U.S. Environmental Protection Agency. (2025). Registration decision for the new active ingredient Vadescana dsRNA and the two associated end-use products Norroa and Norroa EZ. Docket EPA-HQ-OPP-2023-0558.

U.S. Environmental Protection Agency. (2025). Vadescana double-stranded RNA; exemption from the requirement of a tolerance. Federal Register, 90, 25155.