Abstract

Since the discovery of RNA interference (RNAi) in the nematode wormCaenorhabditis elegansin 1998 by Fire and Mello et al., strides have been made in exploiting RNAi for therapeutic applications and more recently for highly selective insect pest control. Although triggering mRNA degradation in insects through RNAi offers significant opportunities in crop protection, the application of environmental naked dsRNA is often ineffective in eliciting a RNAi response that results in pest lethality. There are many possible reasons for the failed or weak induction of RNAi, with predominant causes being the degradation of dsRNA in the formulated pesticide, in the field or in the insect once ingested, poor cuticular and oral uptake of the nucleic acid and sometimes the lack of an innate strong systemic RNAi response. Therefore, in the last 10 years significant research effort has focused on developing methods for the protection and delivery of environmental dsRNA to enable RNAi-induced insect control. This review focuses on the design and synthesis of vectors (vehicles that are capable of carrying and protecting dsRNA) that successfully enhance mRNA degradation via the RNAi machinery. The majority of solutions exploit the ability of charged polymers, both synthetic and natural, to complex with dsRNA, but alternative nanocarriers such as clay nanosheets and liposomal vesicles have also been developed. The various challenges of dsRNA delivery and the obstacles in the development of well-designed nanoparticles that act to protect the nucleic acid are highlighted. In addition, future research directions for improving the efficacy of RNA-mediated crop protection are anticipated with inspiration taken from polymeric architectures constructed for RNA-based therapeutic applications.

Highlights

  • The Urgent Need for Pesticides With Novel Modes of ActionThe world population is increasing rapidly, and food supply must rise to meet demand

  • Future research must focus on specific management strategies to slow the development of this resistance, in species that are already refractory to RNA interference (RNAi)

  • Many novel nanoparticle delivery vehicles for double stranded-RNA (dsRNA) have been developed, including self-assembled block and branched copolymer nanoparticles, dendrimers, inorganic nanoparticles, and natural product-based nanoparticles, see Figure 3. It is worth noting at this stage that the majority of dsRNA delivery solutions utilise the electrostatic interaction between the anionic phosphate backbone of dsRNA and some cationic character expressed on the nanoparticle vector to assemble a system capable of protecting and transporting the dsRNA

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Summary

Introduction

The Urgent Need for Pesticides With Novel Modes of ActionThe world population is increasing rapidly, and food supply must rise to meet demand. A variety of biological-based insecticides, such as the bacterial toxins of Bacillus thuringiensis (Bt) and Saccharopolyspora spinosa, have been developed as alternatives to the synthetic chemical pesticides. These have modes of action quite distinct from the traditional synthetic chemicals, and whilst this minimises the risk of cross-resistance, field resistance has been widely reported for both biologicals (McGaughey, 1994; Scott, 2008; Bravo et al, 2011; Borel, 2017; Abbas, 2018; Santos and Pereira, 2020). Future research must focus on specific management strategies to slow the development of this resistance, in species that are already refractory to RNAi

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