Does RNAi-Based Technology Fit within EU Sustainability Goals?

European Union (EU) and global sustainability policies emphasize the need to replace contentious pesticides with safe, efficient, cost-effective alternatives ensure sustainable food production. However, R&D for are lagging behind be broadened. Here, we discuss how RNAi-based technology can contribute pesticide risk reduction. Future Agriculture: Ensuring Sustainable Food Production in EUThe Farm-to-Fork (F2F) strategyi, one of pillars underneath Commission’s new Green Deal, aims a more food-secure society. Its include reduction agrochemical inputs, such as pesticides, fertilizers, antimicrobials, achieve greater health, reduce loss biodiversity while ensuring continued crop protection. It envisages various practices that promote lesser usage, integrated pest management (IPM), use precision agriculture artificial intelligence. also recommends imposing maximum levels (tolerances) residues imported commodities enforce production countries exporting EU. The F2F strategy’s measures cited by concurrent Biodiversity Strategy 2030ii, means towards reversing alarming decline farmland birds insects (especially pollinating ones). proposes IPM establishment variable landscapes hospitable natural regulators. Furthermore, it organic farming cover 25% agricultural land 2030, suggests establishing forests resilient pests, banning chemical from urban green spaces.At same time, Commission published report on experience gained its policy under so-called ‘Sustainable Use Directive’ (SUD) 2009iii. Under SUD, EU member states had develop implement national action plans volumes risk. concluded prevalent shortcoming across board was lack assessment actual implementation practices, there an upward trend non-chemical, low-risk, basic active substances, basis should Notably, biopesticide producers’ organization (European Crop Protection Association; ECPA) recently pledged support these commitments focused innovation, sustainability, including €14 billion investment development techniques targeted (hence reduced) application biopesticides favorable characteristics, complementing other pesticidesiv. Concurrent EU’s less risky United Nations Environmental Program (UNEP), international organizations, companies proactively pursuing ‘highly hazardous pesticides’.As already noted review SUD implementation, has been needs make case innovative, enabling technologies using versatile platforms agents widely applicable host different pests diseases, yielding products high specificity or disease, benign environmental health profile, requiring short time affordable costs.RNAi-Based Technology Enables Pesticide Risks Reduction GoalsRNAi is well-known biological process most eukaryotes, where double-stranded RNA (dsRNA) molecules regulate gene expression targeting specific endogenous mRNA sequence-specific manner (Figure 1). By exploiting this sequence-dependent mode action, higher selectivity better safety profiles (less mobile through soil, persistent, toxic) compared being developed [1.Wang M. et al.Bidirectional cross-kingdom RNAi fungal uptake external RNAs confer plant protection.Nat. Plants. 2016; 2: 1-10Crossref Scopus (339) Google Scholar, 2.Koch A. al.An control Fusarium graminearum infections spraying long dsRNAs involves passage controlled silencing machinery.PLoS Pathog. 12e1005901Crossref PubMed (257) 3.Mitter N. al.Clay nanosheets topical delivery sustained protection against viruses.Nat. 2017; 3: (400) 4.Jin S. al.Engineered chloroplast dsRNA silences cytochrome p450 monooxygenase, V-ATPase chitin synthase genes insect gut disrupts Helicoverpa armigera larval pupation.Plant Biotechnol. J. 15: 145Crossref (3) Scholar]. several unique features offer additional opportunities pesticides. designed target without change and, depending pest, outcomes ranging sublethal lethal effects achieved. Although selecting effective targets challenging step, combination availability silico tools increase genome databases species made possible design species-selective efficient zero negligible off-target non-target [5.Bachman P.M. al.Ecological DvSnf7 RNA: plant-incorporated protectant activity western corn rootworm.Regul. Toxicol. Pharmacol. 81: 77-88Crossref (61) Scholar,6.Taning C.N.T. al.A sequence complementarity-based approach evaluating transcript knockdown Bombus terrestris, following ingestion pest-specific dsRNA.J. Pest. Sci. 2021; 94: 487-503Crossref (12) This presents advantage over current broad spectra, usually affecting species. Additionally, molecule rapidly degraded nucleases UV radiation [7.Bachman al.Environmental fate dissipation applied aquatic systems, plants.Front. Plant 2020; 11: 21Crossref (29) Scholar,8.Parker K.M. interference pesticides: Adsorption degradation soils.Environ. Technol. 2019; 53: 3027-3036Crossref (49) Scholar], contrast some longer persistence environment.RNAi-based biocontrol two main approaches: planta genetically modified (GM) crops exogenous formulated 2). GM plants differ expressing proteins because introduced sequences give rise stable small very compounds. Moreover, expressed (s)RNAs highly vascular system, allowing horticultural acquire resistance when grafted onto transgenic rootstocks [9.Zhao D. al.Transfer between branches scions sweet cherry trees.PLoS ONE. 15e0236376PubMed type particular interest seed nursery industries, which mainly interested propagating marketing resistant high-quality varieties. Nevertheless, toward favored treated not considered organisms (GMOs) [10.Shew al.New innovations biotech: consumer acceptance rice production.Food Control. 189-195Crossref (23) These directly spray application, trunk injection tree species, soaking, root drenching hydroponic systems greenhouses. possibility developing exogenously profile stimulated creation start-up (albeit at moment mostly non-European) exploit available biotechnology field-scale applicationsv,vi.Figure 2Two Main Delivery Approaches RNAi-Based Control Pests Diseases.Show full captionRNAi-based typically starts designing (ds)RNA essential pathogen, remaining safe organisms. genome/transcriptome sophisticated high-throughput approaches, RNA-seq digital tag (DGE-tag) technologies, significantly improved selection potential targets. help pathogen-specific molecules, empirical evidence bioassays required effectiveness pest/pathogen adverse There approaches control; constructs pests/pathogens, second dsRNA. choice method depends interaction pest/pathogen, feasibility pest/pathogen. follow separate paths during product pipeline, falling organism (GMO) regulation, expected fall (PPP) regulation. challenged technological modify cost registration GMO, public opposition GMOs. producing large-scale field appropriate formulation improve efficiency recalcitrant pests/pathogens. Despite challenges, both have successfully led products, reducing pesticides.View Large Image Figure ViewerDownload Hi-res image Download (PPT)As spin-off severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) pandemic, existing capacity may ramped up exponentially near future provide community RNA-based vaccines, owing substantive private investments running into hundreds millions dollarsvii. could converted (with stringent quality requirements than biomedicines) purposes. would further manufacture sizable needed applications. significant improvements pathogens [3.Mitter Formulations generally either stability and/or pathogens, thereby improving efficiency. Developing right pathogens. As such, performed case-by-case basis. At strategy directed interests agribusinesses invest biosafety [11.Mat Jalaluddin N.S. al.Global trends research commercialization crops.Crit. Rev. 39: 67-78Crossref (30) coupled stimulation development, indicate goal strategy.Societal Perception Acceptance BiocontrolAlternatives address increased acknowledged science [12.Kates R.W. al.Sustainability science.Science. 2001; 292: 641-642Crossref (1967) Scholar] term used media but still complex concept public. Consumer perceptions often studied perception linked [13.Remoundou K. al.Pesticide perceptions, knowledge, attitudes operators, workers, residents: literature.Hum. Ecol. Risk. Assess. 2014; 20: 1113-1138Crossref (36) important explicitly risks benefits capture trade-offs consumers willing accept generations Perceived alone might decisive factor societal relevant factors, extent perceived necessary, unimportant, shape [14.Gupta al.Ethics, associated applications nanotechnology: comparison expert drivers acceptance.NanoEthics. 2015; 9: 93-108Crossref (60) Therefore, fundamental importance dialog stakeholders ethical social concerns addressed early strategies. If attitude remains uncrystallized, constant re-evaluation what think advised [15.Fischer A.R. al.Attitudes attitudinal ambivalence nanotechnology production.Public Underst. 2013; 22: 817-831Crossref (37) unlikely fixed rather influenced events, order entry market. Findings evaluations communication strategies drive strategies.Concluding Remarks PerspectivesThe makes them conventional agrochemicals promising solution substitute reliance general. enable society key tasks will accomplished. co-creation new, effective, collaboration responsible innovation paradigm promoted EU, foster knowledge technology. advancement understanding consumers’ facilitate successful market introduction RNAi-based, costs. spaces. pesticides’. applicationsv,vi.As strategy. environment. applicationsv,vi. Societal Alternatives Concluding article based upon work COST Action CA 15223 iPLANTA, supported Cooperation Science Technology), www.cost.eu. B.M. received funding MIUR-PRIN2017 program via Grant No. 20173LBZM2 -Micromolecule, C.N.T.T. G.S. Special Research Fund Ghent University (BOF) Foundation—Flanders (FWO), G.K. Netherlands Ministry Agriculture, Nature Quality International Pure Applied Chemistry . Resourcesihttps://ec.europa.eu/food/sites/food/files/safety/docs/f2f_action-plan_2020_strategy-info_en.pdfiihttps://eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX:52011DC0244iiihttps://ec.europa.eu/food/plant/pesticides/sustainable_use_pesticides_enivwww.ecpa.eu/commitments/2030-commitments/innovation-investmentvwww.agrorna.com/sub_05.htmlviwww.greenlightbiosciences.com/markets/plant-sciences/viiwww.greenlightbiosciences.com/covid19/ ihttps://ec.europa.eu/food/sites/food/files/safety/docs/f2f_action-plan_2020_strategy-info_en.pdf iihttps://eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX:52011DC0244 iiihttps://ec.europa.eu/food/plant/pesticides/sustainable_use_pesticides_en ivwww.ecpa.eu/commitments/2030-commitments/innovation-investment vwww.agrorna.com/sub_05.html viwww.greenlightbiosciences.com/markets/plant-sciences/ viiwww.greenlightbiosciences.com/covid19/