Effective delivery and selective insecticidal activity of double-stranded RNA via complexation with diblock copolymer varies with polymer block composition.

Autor: Pugsley CE; School of Chemical and Process Engineering, University of Leeds, Leeds, UK.; School of Biology, Faculty of Biological Sciences, University of Leeds, Leeds, UK., Isaac RE; School of Biology, Faculty of Biological Sciences, University of Leeds, Leeds, UK., Warren NJ; School of Chemical and Process Engineering, University of Leeds, Leeds, UK., Stacey M; School of Biology, Faculty of Biological Sciences, University of Leeds, Leeds, UK., Ferguson CTJ; School of Chemical and Process Engineering, University of Leeds, Leeds, UK.; School of Biology, Faculty of Biological Sciences, University of Leeds, Leeds, UK., Cappelle K; Syngenta Ghent Innovation Center, Gent-Zwijnaarde, Belgium., Dominguez-Espinosa R; Syngenta Jealott's Hill International Research Centre, Bracknell, UK., Cayre OJ; School of Chemical and Process Engineering, University of Leeds, Leeds, UK.
Jazyk: angličtina
Zdroj: Pest management science [Pest Manag Sci] 2024 Feb; Vol. 80 (2), pp. 669-677. Date of Electronic Publication: 2023 Oct 25.
DOI: 10.1002/ps.7793
Abstrakt: Background: Chemical insecticides are an important tool to control damaging pest infestations. However, lack of species specificity, the rise of resistance and the demand for biological alternatives with improved ecotoxicity profiles means that chemicals with new modes of action are required. RNA interference (RNAi)-based strategies using double-stranded RNA (dsRNA) as a species-specific bio-insecticide offer an exquisite solution that addresses these issues. Many species, such as the fruit pest Drosophila suzukii, do not exhibit RNAi when dsRNA is orally administered due to degradation by gut nucleases and slow cellular uptake pathways. Thus, delivery vehicles that protect and deliver dsRNA are highly desirable.
Results: In this work, we demonstrate the complexation of D. suzukii-specific dsRNA for degradation of vha26 mRNA with bespoke diblock copolymers. We study the ex vivo protection of dsRNA against enzymatic degradation by gut enzymes, which demonstrates the efficiency of this system. Flow cytometry then investigates the cellular uptake of Cy3-labelled dsRNA, showing a 10-fold increase in the mean fluorescence intensity of cells treated with polyplexes. The polymer/dsRNA polyplexes induced a significant 87% decrease in the odds of survival of D. suzukii larvae following oral feeding only when formed with a diblock copolymer containing a long neutral block length (1:2 cationic block/neutral block). However, there was no toxicity when fed to the closely related Drosophila melanogaster.
Conclusion: We provide evidence that dsRNA complexation with diblock copolymers is a promising strategy for RNAi-based species-specific pest control, but optimisation of polymer composition is essential for RNAi success. © 2023 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
(© 2023 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.)
Databáze: MEDLINE
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