CUADb-based oligonucleotide insecticides and RNA biocontrols: molecular bases and potential in plant protection

Recent advances in molecular genetics, nucleic acid synthesis, and bioinformatics have pro-vided novel opportunities for plant 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: DNA containment (DNAc), employing oligonucleotide insecticides based on contact unmodified antisense DNA biotechnology (CUADb), also known as genetic zipper technology, and 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 function of RNA in gene silencing through interference (RNAi) has been documented in the late1990s as an antiviral immune response in nematodes, the CUADb antisense approach initially emerged as a powerful strategy for pest control against lepidopterans in 2008. CUADb approach relies on disrupting rRNA biogenesis and ribosome production, a process entirely distinct from RNAi. The efficacy of these approaches appears to be species dependent: while CUADb demonstrates optimal activity against Sternorrhyncha (e.g., aphids, mealybugs, psyllids, scale insects), thrips, and mites, 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 mechanism of action and the current challenges facing their adoption.