Oligonucleotide Insecticides for Green Agriculture: Regulatory Role of Contact DNA in Plant–Insect Interactions

Abstract

Insects vastly outnumber us in terms of species and total biomass, and are among the most efficient and voracious consumers of plants on the planet. As a result, to preserve crops, one of the primary tasks in agriculture has always been the need to control and reduce the number of insect pests. The current use of chemical insecticides leads to the accumulation of xenobiotics in ecosystems and a decreased number of species in those ecosystems, including insects. Sustainable development of human society is impossible without useful insects, so the control of insect pests must be effective and selective at the same time. In this article, we show for the first time a natural way to regulate the number of insect pests based on the use of extracellular double-stranded DNA secreted by the plant Pittosporum tobira. Using a principle similar to one found in nature, we show that the topical application of artificially synthesized short antisense oligonucleotide insecticides (olinscides, DNA insecticides) is an effective and selective way to control the insect Coccus hesperidum. Using contact oligonucleotide insecticide Coccus-11 at a concentration of 100 ng/μL on C. hesperidum larvae resulted in a mortality of 95.59 ± 1.63% within 12 days. Green oligonucleotide insecticides, created by nature and later discovered by humans, demonstrate a new method to control insect pests that is beneficial and safe for macromolecular insect pest management.

CUAD biotechnology offers 0.5 USD per hectare for aphid control: innovative platform for low-cost plant protection

“…Moreover, ITS regions of rRNA genes are moderately variable (Figure 4) in comparison with regions of 18S, 5.8S, and 28S rRNAs [35] allowing the creation of unique sequences of oligonucleotide insecticides. The length of an oligonucle-otide insecticide ∼ 11 nt makes it possible to create selective oligonucleotide insecticides with a uniqueness frequency equal to 1/4.19·10 6 and is obviously enough to be used in most agrocenoses [36].…”

Oligonucleotide insecticides (contact unmodified antisense DNA biotechnology) and RNA biocontrols (double-stranded RNA technology): newly born fraternal twins in plant protection

“…Due to the ribose residues, double-stranded RNA fragments are more susceptible to hydrolysis in nature than DNA (Williams et al, 2017), and the large length of the fragment makes the selectivity of such insecticides less controllable and additionally forces one to calculate possible risks for non-target organisms (Roberts et al, 2015; Christiaens et al, 2021). For RNA biocontrols to be effective more different insect pest RNAs (Liu et al, 2020) can be chosen for degradation than with oligonucleotide insecticides (Oberemok et al, 2022). Both classes of new generation insecticides have cost-effective methods for their synthesis: liquid-phase phosphoramidite synthesis of DNA (Gal’chinsky et al, 2023) and cell-free production of RNA (Taning et al, 2020).…”

“…Due to the development of genetic resistance, this process never stops (Sparks et al, 2021; Mogilicherla and Roy, 2023) and it is possible to improve duration of operational life, selectivity in action, increased biodegradability, and low carbon footprint of current insecticides. Obviously, biomolecules are most likely to have such characteristics (Christiaens et al, 2020; Oberemok et al, 2022; Palli, 2023; Gal’chinsky et al, 2024). Technologies in plant protection evolved and created opportunity of development of insecticides based on natural polymers, DNA and RNA, having the characteristics which past generations of chemical insecticides have never had (Oberemok et al, 2018a; Rank and Koch, 2021; Oberemok et al, 2023; Koeppe et al, 2023).…”

“…In addition, it was assumed that rRNA is resistant to degradation by antisense DNA oligonucleotides (Will and Luhrmann, 2001; Bachellerie et al, 2002). Oligonucleotide insecticides (briefly, olinscides, or DNA insecticides) have shifted the old paradigm and marked the formation of a new paradigm in which unmodified oligodeoxyribonucleotides are capable of causing both, down-regulation and up-regulation of target genes during DNA containment mechanism (Oberemok et al, 2022; Gal’chinsky et al, 2024). DNA containment mechanism is comprised of 2 steps.…”

“…Ribosomal RNA makes it possible, on the one hand, to use itself as an advantageous because it comprises majority of cell RNA, whereas, on the other hand, it is sufficiently variable among organisms to create well-tailored insecticides (Gal’chinsky et al, 2024). The length of an oligonucleotide insecticide ∽ 11 nt makes it possible to create selective oligonucleotide insecticides with a uniqueness frequency equal to 1/4.19·10 6 , obviously enough to be used in most agrocenoses (Oberemok et al, 2022). We believe that contact delivery of unmodified antisense DNA (CUADs) is much more efficient than oral delivery of unmodified antisense DNA (ODUADs) because of active DNases present in digestive tract.…”