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

Auburn University, Auburn AL

Investigators

Abstract

NON-TECHNICAL SUMMARY New 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 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 SUMMARY Adopting 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.