Effective delivery and selective insecticidal activity of double-stranded RNA via complexation with diblock copolymer varies with polymer block composition.
Effective delivery and selective insecticidal activity of double-stranded RNA via complexation with diblock copolymer varies with polymer block composition.
复制标题
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随聚合物嵌段组成而变化。
DOI：
10.1002/ps.7793
复制
发表时间：
2023
影响因子：
4.1
通讯作者：
Pugsley CE
中科院分区：
文献类型：
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作者：
Pugsley CE
化学杀虫剂是控制有害虫害的重要工具。然而，缺乏物种特异性、抗药性的增加以及对具有更好生态毒性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致解决方案。许多物种，如水果害虫Drosophila suzukii，当口服dsRNA时，由于肠道核酸酶的降解和缓慢的细胞摄取途径，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。Suzukii-特异性dsRNA用于用定制的二嵌段共聚物降解vha 26 mRNA。我们研究了离体保护dsRNA免受肠道酶的酶降解，这证明了该系统的有效性。然后流式细胞术研究Cy 3标记的dsRNA的细胞摄取，显示用复合物处理的细胞的平均荧光强度增加10倍。聚合物/dsRNA复合物诱导D.仅当用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，才能在经口喂养后产生Suzukiilarbazole。然而，没有毒性时，喂养密切相关的果蝇melanogaster. CONCLUSION我们提供的证据表明，dsRNA复合物与二嵌段共聚物是一个有前途的策略，为RNAi的物种特异性害虫控制，但优化的聚合物组合物是必不可少的RNAi的成功。© 2023 The Authors.Pest Management Sciencepublished by John Wiley & Sons Ltd代表化学工业协会。
BACKGROUNDChemical 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 pestDrosophila 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.RESULTSIn this work, we demonstrate the complexation ofD. suzukii‐specific dsRNA for degradation ofvha26mRNA with bespoke diblock copolymers. We study theex vivoprotection 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 ofD. suzukiilarvae 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 relatedDrosophila melanogaster.CONCLUSIONWe 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 Sciencepublished by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.