Formulation problem or Problem formulation?

Explainer by PhD fellow Kornelia Serwatowska, University of Copenhagen
Kornelia Serwatowska

Making dsRNA Work Better May Also Change Its Risk

When we talk about insecticides, we often focus on the chemicals or the active ingredient that kills the intended insect. But for biopesticides, such as double-stranded RNA-based plant protection products, the “packaging” may be just as important as the molecule itself.

Over the years, the safety and the public awareness have grown, and the harmful pesticides are being slowly phased out of agriculture. In addition to that, due to repetitive usage and/or incorrect application of traditional pesticides, some pests have developed resistance. In response to this challenging situation, research laboratories, biotech companies and the pesticide industries have started working on developing a new generation of "biopesticides". Those are the agents that incorporate natural methods for pest control. Nowadays, the techniques of molecular biology have allowed scientists to develop more sophisticated versions of the mechanisms already provided by solutions present in nature.

RNA-based biopesticides are one of those new developments which give a promise of targeting a harmful pest "precisely". In theory, this might be one of the most exciting aspects of double-stranded RNA, or dsRNA: it can be designed to target genes in a specific pest species while keeping other species safe.

But in practice, the active dsRNA molecule is only part of the story. A major challenge for dsRNA-based plant protection products is delivery. Naked dsRNA can be unstable. It may degrade in the environment, on plant surfaces, or inside the gut of an insect before it reaches the cells where it needs to act. To solve this, researchers are developing different ways to overcome those challenges by protecting the dsRNA by encapsulating it with delivery agents – formulations. Examples of commonly used materials for these formulations are: chitosan, liposomes, clay or peptides. Those materials could protect dsRNA and improve its uptake.

Problem formulation

= critical foundational step in a risk assessment. This step defines the risk question: what could cause harm, which organisms may be exposed, and what evidence is needed. In my PhD, it helps me decide which questions I need to answer to know how dsRNA may affect non-target species.

This is where my PhD project begins. I am interested in what could be called “the formulation problem”: the same packaging that makes dsRNA more effective against a pest may also change how it behaves in the environment and how non-target organisms are exposed. An encapsulation type may increase uptake of the dsRNA, prolong its persistence, improve movement through the plant, or affect transfer through food chains. These are useful properties if the goal is pest control, but it is also important to investigate them from an environmental safety perspective. In my research, I will focus on whether the enclosure type of the dsRNA changes the effects on the target species (those meant to be eliminated by the pesticide) and non-target species (those that should stay unharmed by the pesticide).

In short, the formulation may be more than just “packaging” for the dsRNA. It can affect how long the dsRNA stays active, how easily it enters plants or organisms, and which species may be exposed to it. This is important for risk assessment. Before we can judge whether a dsRNA-based pesticide is safe, we first need to ask the right questions. This process in the risk assessment is called Problem formulation. It means clearly defining what we need to assess: where the product goes in the environment, which organisms might come into contact with it, and what effects it could have.

Agrochemical formulations

= precise combinations of active ingredients and inert formulants (adjuvants, solvents, and carriers, nanomaterials) designed to make crop protection products safe, stable, and easy to apply. Because raw active ingredients are rarely usable on their own, the right formulation (e.g. chitosan, liposomes, clay or peptides) dictates efficacy, application method, and environmental safety.

Therefore, the aim of my PhD is not only to ask whether dsRNA has an effect, but to understand why and how the formulation changes exposure, uptake and biological responses. This work contributes to the broader ENSAFE goal of supporting the development of a regulatory framework for new bio-based plant protection products. In conclusion, perhaps dsRNA-based pesticides, safety assessment (Problem formulation) may need to consider not only the active ingredient, but also the carrier (Formulation) that delivers it.