Protection of double-stranded RNA for delivery through complexation with block copolymers: optimising polymer architecture for Drosophila suzukii-specific control

Chemical insecticides are a typical tool used by growers to control pest insect species, such as the invasive fruit fly Drosophila suzukii. However, the rise of resistance to common chemical pesticides and widespread concerns of eco-toxicity has led to an increasing demand for biological alternatives with new modes-of-action and improved biosafety profiles.

RNA interference, discovered in 1998 by Fire and Mello et al., can be exploited as a species-specific method of pest control. The application of exogenous double-stranded RNA to cells can induce the degradation of pre-determined mRNA transcripts, which can result in enhanced mortality of an insect pest if specific transcripts are targeted.

Induction of systemic RNAi can be generated in select insect species through oral administration of dsRNA. However, many insect species such as dipterans or lepidopterans are recalcitrant to RNAi through oral feeding of dsRNA. This is due to degradation of the orally delivered dsRNA by RNases in the haemolymph, saliva and intestines of the insect, or within the environment prior to ingestion. Drosophila in particular show low cellular uptake of dsRNA, due to the lack the SID-1-like transporter protein that ordinarily provides a faster cellular uptake pathway in comparison to endocytosis.

Polymeric delivery vehicles can therefore be developed to protect dsRNA against enzymatic degradation, and to enhance cellular uptake to induce insect mortality and thus pest management through RNAi-based control. This thesis describes the design, synthesis, characterisation, and ex vivo, in vitro and in vivo biological assessment of novel block copolymers, to act as protective vehicles for dsRNA for species-specific bio-insecticidal activity in Drosophila suzukii.