Design of Lipopeptides and dsRNA-Lipopeptide Complexes for Sprayable RNAi-Based Plant Protection

Broad-spectrum insecticides persist in the environment, affecting non-target organisms and selecting for resistant pest populations. In contrast, RNA interference (RNAi) achieves species-targeted pest control triggered by the delivery of exogenous double-stranded RNA (dsRNA), which is biodegradable and broken down into harmless components by nucleases. Sprayable applications require suitable formulation strategies for dsRNA protection during delivery. Here, we describe the preparation of dsRNA-lipopeptide complexes (LPCs) composed of non-toxic short-chain lipopeptide surfactants by microfluidic mixing, yielding positively charged dispersions of LPCs < 200 nm in diameter, which encapsulate and protect dsRNA from enzymatic degradation. Some lipopeptides were found to undergo thermo-reversible gelation, self-assembling to fibrillar nanostructures, but remained effective for dsRNA delivery to induce mortality in Colorado potato beetle larvae feeding on sprayed plants. Our results show that lipopeptide surfactants are suitable for the formulation of dsRNA to enable effective delivery to pest insects.