Block copolymer-dsRNA complexes for crop protection

用于作物保护的嵌段共聚物-dsRNA 复合物

• 批准号: 2746546
• 金额: --
• 依托单位: University of Leeds
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2746546
• 关键词: Block; copolymer; dsRNA; complexes; crop

The use of pesticides has allowed crop production to more than double over the last 60 years, reaching 9 billion tonnes in 2018 and keeping up with increasing food and plant-derived products demand due to population growth [1]. However, their excessive use has led to negative impacts on the environment and to human health and off-target species [1]. This has contributed to the development of alternative pest control measures that target only specific species while minimising off-target toxicity effects.One such alternative is RNAi-based biopesticides that can be tuned to match specific pest genes and reduce the possibility of non-target damage. In this method, a double-stranded RNA molecule (dsRNA) is delivered to pests, stunting their growth or potentially causing pest death by selective gene silencing. Delivery vectors have been developed to protect RNA from degradation in the many environments it encounters before reaching the target sites within the pests. Recently a hydrophilic di-block copolymer has been synthesised for this purpose, where the cationic PQDMAEMA block binds to the negatively charged dsRNA and the neutral PDMA block provides steric stabilisation to prevent aggregation of the resulting polymer-dsRNA complexes, which were shown to effectively bind to and protect dsRNA [2].In addition to protecting dsRNA, complexes should allow dsRNA release once within the pest's cells. To this end, this project will build upon the previously synthesised copolymer to include pH-responsiveness into polymer design. More specifically, both permanently quaternised (QDMAEMA) and pH-dependently quaternised (DMAEMA) monomers will be used to synthesise the cationic block. This block will then have a variable positive charge depending on the pH of its environment, which is expected to induce the triggered release of dsRNA under targeted conditions. Anticipated results include reproducing synthesis and characterisation techniques of previous polymers and complexes and testing a machine learning algorithm to relate polymer properties to complexes' performance based on collaborator data.

农药的使用使作物产量在过去60年中翻了一番以上，2018年达到90亿吨，并跟上了人口增长导致的粮食和植物衍生产品需求的增长[1]。然而，它们的过度使用导致了对环境、人类健康和非目标物种的负面影响[1]。这有助于开发仅针对特定物种的替代害虫控制措施，同时最大限度地减少脱靶毒性效应。其中一种替代方法是基于RNAi的生物农药，其可以调整以匹配特定害虫基因并减少非靶标损害的可能性。在这种方法中，双链RNA分子（dsRNA）被递送到害虫，通过选择性基因沉默抑制它们的生长或潜在地导致害虫死亡。已经开发了递送载体以保护RNA在到达害虫内的靶位点之前在其遇到的许多环境中免于降解。最近已经合成了一种亲水性二嵌段共聚物用于此目的，其中阳离子PQDMAEMA嵌段结合带负电荷的dsRNA，中性PDMA嵌段提供空间稳定性以防止所得聚合物-dsRNA复合物的聚集，所述复合物显示出有效地结合并保护dsRNA [2]。除了保护dsRNA之外，复合物应该允许dsRNA一旦在害虫细胞内释放。为此，该项目将建立在以前合成的共聚物，包括pH响应到聚合物设计。更具体地，永久季铵化（QDMAEMA）和pH依赖性季铵化（DMAEMA）单体将用于合成阳离子嵌段。然后，该嵌段将具有可变的正电荷，这取决于其环境的pH，预期其在靶向条件下诱导dsRNA的触发释放。预期结果包括再现先前聚合物和复合物的合成和表征技术，并测试机器学习算法，以基于合作者数据将聚合物特性与复合物的性能相关联。