双链RNA通过与二嵌段共聚物络合的有效递送和选择性杀虫活性因聚合物嵌段组成而异。

IF 3.8 1区农林科学 Q1 AGRONOMY

Pest Management Science Pub Date : 2023-09-27 DOI:10.1002/ps.7793

Charlotte E. Pugsley, R. Elwyn Isaac, Nicholas J. Warren, Martin Stacey, Calum T. J. Ferguson, Kaat Cappelle, Rosa Dominguez-Espinosa, Olivier J. Cayre

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引用次数: 0

摘要

背景：化学杀虫剂是控制有害生物侵扰的重要工具。然而，由于缺乏物种特异性、耐药性的上升以及对具有改善的生态毒性特征的生物替代品的需求，意味着需要具有新作用模式的化学品。使用双链RNA（dsRNA）作为物种特异性生物杀虫剂的基于RNA干扰（RNAi）的策略提供了解决这些问题的精细解决方案。许多物种，如果蝇，在口服dsRNA时，由于肠道核酸酶降解和细胞摄取途径缓慢，不会表现出RNAi。因此，保护和递送dsRNA的递送载体是非常需要的。结果：在这项工作中，我们证明了suzukii D.特异性dsRNA与定制的二嵌段共聚物复合降解vha26mRNA。我们研究了dsRNA对肠道酶促降解的离体保护作用，这证明了该系统的有效性。流式细胞术然后研究Cy3标记的dsRNA的细胞摄取，显示用多肽处理的细胞的平均荧光强度增加了10倍。只有当与含有长中性嵌段长度（1∶2阳离子嵌段/中性嵌段）的二嵌段共聚物形成时，聚合物/dsRNA复合物才能在口服喂养后显著降低铃木虫幼虫87%的存活几率。然而，喂食亲缘关系密切的黑腹果蝇时没有毒性。结论：因此，我们提供了证据，证明dsRNA与二嵌段共聚物复合是一种很有前途的基于RNAi的物种特异性害虫防治策略，然而，优化聚合物组成对RNAi的成功至关重要。这篇文章受版权保护。保留所有权利。

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

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

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.

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来源期刊

Pest Management Science 农林科学-昆虫学

CiteScore

7.90

自引率

9.80%

发文量

553

审稿时长

4.8 months

期刊介绍： Pest Management Science is the international journal of research and development in crop protection and pest control. Since its launch in 1970, the journal has become the premier forum for papers on the discovery, application, and impact on the environment of products and strategies designed for pest management. Published for SCI by John Wiley & Sons Ltd.