CAREER: Branched Amphiphilic Peptide Capsules (BAPCs) for the delivery of lethal dsRNA into invasive organisms

事业：分支两亲肽胶囊 (BAPC) 用于将致命的 dsRNA 传递到入侵生物体中

• 批准号: 2340070
• 负责人: Adriana Avila-Flores
• 金额: $ 63万
• 依托单位: Auburn University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2024
• 资助国家: 美国
• 起止时间: 2024-09-01 至 2029-08-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2340070&HistoricalAwards=false
• 关键词: CAREER; Branched; Amphiphilic; Peptide; Capsules

NON-TECHNICAL SUMMARYNew and innovative pesticides are urgently needed to address several challenges including resistance to current treatments, unintended harm to important species like pollinators, and environmental damage. One promising approach involves using double-stranded RNA (dsRNA) to disrupt essential genes in insects specifically targeting harmful species while sparing beneficial ones. Recent studies have revealed that when dsRNA is combined with nanomaterials, its effectiveness significantly increases. This combination prevents premature degradation of dsRNA and helps it get absorbed into the cells of insect guts. This project aims to explore how specific properties of nanomaterials influence the performance of dsRNA-based biopesticides. Researchers will work with a unique nanomaterial made of peptides and study how variations in size, charge, and composition impact dsRNA absorption, insect survival, and stability in different environmental conditions. The outcomes of this study are significant as they advance our understanding of designing biomaterials for agricultural use, potentially leading to the creation of new safe pesticides. Additionally, the project aims to involve students in science, especially those from historically excluded groups through hands-on experiences. The research team will educate students in Alabama about the potential of nanomaterials as pesticides through programs at Auburn University. High school students participating in these experiments will improve their understanding and interest in science contributing to their engagement in STEM fields.This project is jointly funded by the Biomaterials Program and the Established Program to Stimulate Competitive Research (EPSCoR).TECHNICAL SUMMARYAdopting alternative strategies for insect pest management is critical to counter challenges posed by pesticide resistance, off-target effects, and environmental harm. Utilizing double-stranded RNA (dsRNA) to knockdown essential genes in insects has emerged as a promising alternative to conventional pesticides. This method targets harmful species without affecting beneficial ones and lacks known insect resistance mechanisms. Recent discoveries demonstrated that association of dsRNA with nanomaterials enhances its efficacy by preventing premature degradation and facilitating uptake by gut cells. The primary objective of this research proposal is to explore how nanomaterial properties influence the lethal effects of dsRNA-based biopesticides. Specifically, this project involves using Branched Amphiphilic Peptide Capsules (BAPCs) combined with dsRNA. BAPCs are a new class of biomaterial developed by the PI that stand out in the crowded field of nanoparticle delivery systems owing to two important factors: 1) BAPCs are assembled exclusively in water, and 2) BAPCs contain four free lysine Ɛ-amino groups with pKa values between 9 and 10.5, which makes them stable in neutral and alkaline insect guts. Previous data demonstrated that BAPC-dsRNA complexes target essential genes in Tribolium castaneum and Acyrthosiphon pisum, leading to high mortality rates in both species. The proposal hypothesizes that by manipulating the size, charge, and composition of BAPCs, it's possible to regulate: 1) the cellular uptake and distribution of dsRNA, as well as its transport across midgut cells, 2) insect survival, and 3) stability against environmental elements. The fall armyworm (Spodoptera frugiperda) and the cotton aphid (Aphis gossypii) will serve as pest models for testing the hypothesis. Beyond the scientific exploration, the proposal also has educational objectives. It seeks to educate Alabama students about the potential of nanomaterials in pest control through K-12 outreach initiatives. Students will actively participate in research-related activities, promoting engagement in STEM fields. Additionally, this proposal aims to contribute to the fundamental understanding of biomaterial design for agricultural purposes and bridge knowledge gaps regarding the role of transcytosis in nanomaterial transport across insect midguts.This project is jointly funded by the Biomaterials Program and the Established Program to Stimulate Competitive Research (EPSCoR).This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

非技术摘要 迫切需要新型创新农药来应对多项挑战，包括对现有治疗方法的耐药性、对授粉媒介等重要物种的意外伤害以及环境破坏，一种有前途的方法是使用双链 RNA (dsRNA) 来破坏昆虫的必需基因。最近的研究表明，当 dsRNA 与纳米材料结合时，其有效性显着提高，可防止 dsRNA 过早降解并帮助其被吸收。该项目旨在探索纳米材料的特定特性如何影响基于 dsRNA 的生物农药的性能，研究人员将使用由肽制成的独特纳米材料，并研究尺寸、电荷和成分的变化如何影响 dsRNA 吸收、昆虫。这项研究的结果意义重大，因为它们增进了我们对设计农业用生物材料的理解，有可能创造出新的安全农药。此外，该项目旨在让学生参与科学、尤其研究小组将通过奥本大学的项目向阿拉巴马州的学生介绍纳米材料作为杀虫剂的潜力，提高他们对科学的理解和兴趣，为他们的生活做出贡献。 STEM 领域的参与。该项目由生物材料计划和刺激竞争研究既定计划 (EPSCoR) 联合资助。技术摘要采用害虫管理的替代策略对于应对农药带来的挑战至关重要利用双链 RNA (dsRNA) 敲低昆虫的必需基因已成为传统杀虫剂的一种有前景的替代方案，这种方法可以针对有害物种，而不影响有益物种，并且缺乏已知的昆虫抗性机制。最近的发现表明，dsRNA 与纳米材料的结合可以通过防止过早降解和促进肠道细胞的吸收来增强其功效。本研究计划的主要目的是探索纳米材料特性如何影响基于 dsRNA 的致死效应。具体来说，该项目涉及使用与 dsRNA 结合的分支两亲肽胶囊（BAPC），BAPC 是 PI 开发的一类新型生物材料，由于两个重要因素，它在众多的纳米颗粒递送系统领域中脱颖而出：1）BAPC。仅在水中组装，2) BAPC 含有四个游离赖氨酸Ɛ-氨基，pKa 值在 9 至 10.5 之间，其中先前的数据表明，BAPC-dsRNA 复合物以赤拟谷盗和豌豆蚜中的必需基因为目标，通过控制大小、电荷和成分，导致这两个物种的高死亡率。 BAPC 可以调节：1) dsRNA 的细胞摄取和分布，及其跨中肠细胞的运输，2) 昆虫存活，3) 稳定性秋粘虫（Spodoptera frugiperda）和棉蚜（Aphis gossypii）将作为测试这一假设的害虫模型，除了科学探索之外，该提案还旨在教育阿拉巴马州的学生了解其潜力。通过 K-12 推广计划，学生将积极参与研究相关活动，促进对 STEM 领域的参与。此外，该提案旨在促进对农业用途和桥梁生物材料设计的基本理解。关于转胞吞作用在纳米材料跨昆虫中肠运输中的作用的知识差距。该项目由生物材料计划和刺激竞争性研究既定计划（EPSCoR）联合资助。该奖项反映了 NSF 的法定使命，并通过评估被认为值得支持利用基金会的智力优势和更广泛的影响审查标准。