# Contact Unmodified Antisense DNA Biotechnology (CUADb)-Based Oligonucleotide Insecticides and RNA Biocontrols: Molecular Bases and Potential in Plant Protection

## TL;DR

This paper reviews two nucleic acid-based technologies, CUADb and RNAi, for controlling insect pests in plants, highlighting their mechanisms and effectiveness against different insect species.

## Contribution

The paper provides a comparative analysis of CUADb and RNAi technologies, emphasizing their distinct molecular mechanisms and species-specific efficacy in pest control.

## Key findings

- CUADb disrupts rRNA biogenesis and is effective against Sternorrhyncha insects like aphids and mites.
- RNAi degrades mRNA and is most effective against beetles from Tenebrionidae and Chrysomelidae families.
- Both technologies show species-dependent efficacy and face challenges in adoption.

## Abstract

Recent advances in molecular genetics, nucleic acid synthesis, and bioinformatics have provided novel opportunities for plants’ protection against insect pests. Currently, both DNA and RNA serve as active insecticidal ingredients, transcending their traditional role as carriers of genetic information. This novel activity is achieved through two fundamentally distinct mechanisms. The first one is DNA containment (DNAc), employing oligonucleotide insecticides based on contact unmodified antisense DNA biotechnology (CUADb), also known as ’genetic zipper’ technology. The second one is RNA interference (RNAi), employing RNA biocontrols based on double-stranded RNA (dsRNA) technology. The investigation of the molecular mechanism underlying the antisense activity of nucleic acids emerged in the early 1960s. While the antisense effects of RNA in gene silencing through interference (RNAi) was documented in the late 1990s as antiviral immune responses in nematodes, the CUADb antisense approach initially emerged as a powerful strategy for pest control against lepidopterans in 2008. The CUADb approach relies on disrupting rRNA biogenesis and ribosome production, while RNAi shows the best results in mRNA degradation and no efficient result is known for rRNA. The efficacy of these approaches appears to be species dependent. For example, CUADb demonstrates optimal activity against Sternorrhyncha (e.g., aphids, mealybugs, psyllids, and scale insects), thrips, and mites. In turn, the RNAi strategy shows a strong insecticidal potential against beetles from the Tenebrionidae and Chrysomelidae families. Here, we will review the differences between the two technologies, their mechanisms of action and the current challenges facing their adoption.