Oligonucleotide insecticides and RNA-based insecticides: 16 years of experience in contact using of the next generation pest control agents
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Cited by 3 publications
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rRNA-specific antisense DNA and dsDNA trigger rRNA biogenesis and cause potent insecticidal effect on insect pestCoccus hesperidumL.
As a completely new principle and new active substance for plant protection, unmodified DNA was shown to function as contact insecticide in 2008. CUAD (contact unmodified antisense DNA) biotechnology is built on the use of short antisense DNA oligonucleotides for insect pest control. Being a novel class of insecticides, oligonucleotide insecticides target pest rRNAs and/or pre-rRNAs and recently showed high insecticidal potential against sap-feeding insect pests, main vectors of plant DNA viruses and one of the most economically-damaging groups of herbivorous insects. In order to use all possible opportunities of CUAD biotechnology, in this article we investigated insecticidal potential of short 11-mer antisense DNA oligos in comparison with long 56-mer single-stranded and double-stranded DNA sequences for Coccus hesperidum control and found lower efficiency of the latter. Also in this article we show that DNA containment (DNAc) mechanism, found on sternorrhynchans, represents interesting and important for insect cell life interplay between rRNAs and different types of DNA oligos. In the course of DNAc, hypercompensation of target rRNA is triggered by all highly and all somewhat complementary DNA oligos but more pronounced later degradation of target rRNA and significant insect pest mortality is seen only in the case of perfect complementarity of oligonucleotides to target rRNA. Oligonucleotide insecticides are effective and safe control agents against sternorrhynchans and other groups of pests, easy to ″tune″ to particular crops with pests, and also flexible to instantly re-create new oligonucleotide insecticides in the case of target-site resistance. Minimalist approach, short antisense DNA dissolved in water, is so potent and selective eco-friendly innovation against sternorrhynchans and other pests, and reveals entirely new dimension to plant protection — DNA–programmable insect pest control. Fundamentally important, this surprising results reveal completely new principle of regulation of rRNA expression in the cell via complementary interaction between rRNAs and unmodified antisense sequences of cell and viral DNA.
rRNA-specific antisense DNA and dsDNA trigger rRNA biogenesis and cause potent insecticidal effect on insect pestCoccus hesperidumL.
As a completely new principle and new active substance for plant protection, unmodified DNA was shown to function as contact insecticide in 2008. CUAD (contact unmodified antisense DNA) biotechnology is built on the use of short antisense DNA oligonucleotides for insect pest control. Being a novel class of insecticides, oligonucleotide insecticides target pest rRNAs and/or pre-rRNAs and recently showed high insecticidal potential against sap-feeding insect pests, main vectors of plant DNA viruses and one of the most economically-damaging groups of herbivorous insects. In order to use all possible opportunities of CUAD biotechnology, in this article we investigated insecticidal potential of short 11-mer antisense DNA oligos in comparison with long 56-mer single-stranded and double-stranded DNA sequences for Coccus hesperidum control and found lower efficiency of the latter. Also in this article we show that DNA containment (DNAc) mechanism, found on sternorrhynchans, represents interesting and important for insect cell life interplay between rRNAs and different types of DNA oligos. In the course of DNAc, hypercompensation of target rRNA is triggered by all highly and all somewhat complementary DNA oligos but more pronounced later degradation of target rRNA and significant insect pest mortality is seen only in the case of perfect complementarity of oligonucleotides to target rRNA. Oligonucleotide insecticides are effective and safe control agents against sternorrhynchans and other groups of pests, easy to ″tune″ to particular crops with pests, and also flexible to instantly re-create new oligonucleotide insecticides in the case of target-site resistance. Minimalist approach, short antisense DNA dissolved in water, is so potent and selective eco-friendly innovation against sternorrhynchans and other pests, and reveals entirely new dimension to plant protection — DNA–programmable insect pest control. Fundamentally important, this surprising results reveal completely new principle of regulation of rRNA expression in the cell via complementary interaction between rRNAs and unmodified antisense sequences of cell and viral DNA.
Biodegradation of insecticides: oligonucleotide insecticides and double-stranded RNA biocontrols paving the way for eco-innovation
Each new class of insecticides that emerged during the development of plant protection gradually found the most suitable group of insect pests for application. At the same time, for each individual insecticide, a balance was sought between its effectiveness, on the one hand, and its safety for non-target organisms and the ecosystem as a whole, on the other hand. Neonicotinoids, diamides and pyrethroids, as effective control agents, dominate the insecticide market, but do not have outstanding performance in selectivity and biodegradation. The biodegradation of insecticides is one of the most important indicators, representing what will be said about the hidden costs for the resulting harvest paid by the environment and human health. Oligonucleotide insecticides (contact unmodified antisense DNA (CUAD) biotechnology, or ‘genetic zipper’ method) and RNA biocontrols (double-stranded RNA technology) as natural polymers and the next-generation classes of insecticides possess unique characteristics in fast biodegradation and high selectivity in action. While current chemical insecticides require days, months and even years for biodegradation by bacteria and fungi, oligonucleotide insecticides and RNA biocontrols are substantially biodegraded within hours in the presence of nucleases. Nucleic acid-based insecticides have the potential to complement the existing insecticide market and set an eco-precedent for crop protection products where the effectiveness of the insecticide will be determined by its safety for non-target organisms, and other factors being equal, the choice of a particular control agent will be determined by its biodegradability. It should be noted that not a single class of insecticides that once appeared has completely disappeared; rather, it has occupied its niche, gradually declining under the pressure of new classes of insecticides. At the same time, the common trend in plant protection is towards use of insecticides with higher biodegradability, which gives hope for a safer future of the planet.
The 'genetic zipper' method offers a cost-effective solution for aphid control
Twenty years ago, it was difficult to imagine the use of nucleic acids in plant protection as insecticides, but today it is a reality. New technologies often work inefficiently and are very expensive; however, qualitative changes occur during their development, making them more accessible and work effectively. Invented in 2008, contact oligonucleotide insecticides (olinscides, or DNA insecticides) based on the CUAD (contact unmodified antisense DNA) platform have been substantially improved and rethought. The main paradigm shift was demonstrating that unmodified antisense DNA can act as a contact insecticide. Key breakthroughs included identifying convenient target genes (rRNA genes), mechanism of action (DNA containment), and discovering insect pests (sternorrhynchans) with high susceptibility to olinscides. Today, the CUAD platform possesses impressive characteristics: low carbon footprint, high safety for non-target organisms, rapid biodegradability, and avoidance of target-site resistance. This next-generation class of insecticides creates opportunities for developing products tailored for specific insect pest populations. The ‘genetic zipper’ method, based on CUAD biotechnology, integrates molecular genetics, bioinformatics, and in vitro nucleic acid synthesis. It serves as a simple and flexible tool for DNA-programmable plant protection using unmodified antisense oligonucleotides targeting pest rRNAs. Aphids, key pests of important agricultural crops, can be effectively controlled by oligonucleotide insecticides at an affordable price, ensuring efficient control with minimal environmental risks. In this article, a low-dose concentration (0.1 ng/µL; 20 mg per hectare in 200 L of water) of the 11 nt long oligonucleotide insecticide Schip-11 shows effectiveness against the aphid Schizolachnus pineti, causing mortality rate of 76.06 ± 7.68 on the 12th day (p<0.05). At a consumption rate of 200 L per hectare, the cost of the required oligonucleotide insecticide is about 0.5 USD/ha using liquid-phase DNA synthesis making them competitive in the market and very affordable for lab investigations. We also show that non-canonical base pairing Golinscide: UrRNA is well tolerated in aphids. Thus, non-canonical base-pairing should be considered not to harm non-target organisms and can be easily solved during the design of oligonucleotide insecticides. The ‘genetic zipper’ method, based on CUAD biotechnology, helps quickly create a plethora of efficient oligonucleotide pesticides against aphids and other pests. Already today, according to our estimations, the ‘genetic zipper’ is potentially capable of effectively controlling 10-15% of all insect pests using a simple and flexible algorithm.
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