Bio‐lethal effect of BAPCs‐dsRNA formulations for genetics‐based pest management

Abstract

The use of RNA interference (RNAi) or double‐stranded RNA (dsRNA)‐mediated gene silencing has become one of the most promising tools on the field of pest management. One of the barriers for RNAi efficiency, however, has being the fact that it needs to be rapidly taken up by cells before being degraded by nucleases. In this context, the nanoscale delivery system formed by Branched Amphiphilic Peptides Capsules (BAPCs™) are proposed as a solution for a safer and more efficient cellular uptake of lethal dsRNA constructs. BAPCs can be synthesized in a varied diameters ranging from 10 to 500 nm. BAPCs act as cationic nucleation centers for nucleic acids, generating peptide‐DNA or dsRNA complexes that are readily taken up by eukaryotic cells, escape late endosomes, and lead to the release of the surface‐bound nucleic acids that alter protein expression. Recently, we described the use of BAPCs for suppressing the translation of genes transcripts related to the unfolded protein response (UPR) in Tribolium castaneum and Acyrthosiphon pisum, which led to a premature death with a 50% increase in lethality when compared to dsRNA alone. For this study, BAPCs were combined with 3 different concentrations of a dsRNA supplied by GreenLight Biosciences™. The test sequence contained ~600 bp. Its lethal bio‐efficacy was compared to the dsRNA by itself on Colorado potato beetle. The tests using unformulated dsRNA at 0.00005, 0.0001 and 0.001, mg/mL exhibited a lethal effect of 10%, 30% and 50% lethality after 8 days by contrast of 30%, 60% and 90% of BAPCs‐dsRNA formulations, followed by approximately 40% reduction on leaf consumption in comparison to the unformulated material. The present results have shown that BAPCs‐dsRNA formulations offer a considerable increase in lethality bio‐efficacy over unformulated dsRNA indicating an additive effect in dsRNA delivery over using dsRNA by itself.Support or Funding InformationThis project is a result of a collaboration between GreenLight Biosciences&[trade], Inc. and Phoreus Biotechnology, Inc.