Risk Assessment Considerations for Genetically Modified RNAi Plants: EFSA’s Activities and Perspective

Papadopoulou, Nikoletta; Devos, Yann; Álvarez‐Alfageme, Fernando; Lanzoni, Anna; Waigmann, Elisabeth

doi:10.3389/fpls.2020.00445

Cited by 39 publications

(33 citation statements)

References 45 publications

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“…This study adds to the conclusions from prior research on various insects that these effects tend to be mediated by high dsRNA concentrations [3,5,25], and it also demonstrates that dsRNA formulations can have significant antifeedant effects for orallydelivered RNAi. Second, there is a need to extend research on the relationship between the number of matching siRNA sequences and RNAi efficacy of dsRNA molecules [16,61,62], so that effective dsRNAs can be designed against single or closely-related pest species that vary in sequence identity with the target gene. Attention to these issues will facilitate the development and deployment of RNAi-based solutions for the management of plant sap-feeding and other insect pests.…”

Section: Discussionmentioning

confidence: 99%

Non-Target Effects of dsRNA Molecules in Hemipteran Insects

Arora

Chung

Douglas

2021

Genes

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Insect pest control by RNA interference (RNAi)-mediated gene expression knockdown can be undermined by many factors, including small sequence differences between double-stranded RNA (dsRNA) and the target gene. It can also be compromised by effects that are independent of the dsRNA sequence on non-target organisms (known as sequence-non-specific effects). This study investigated the species-specificity of RNAi in plant sap-feeding hemipteran pests. We first demonstrated sequence-non-specific suppression of aphid feeding by dsRNA at dietary concentrations ≥0.5 µg µL−1. Then we quantified the expression of NUC (nuclease) genes in insects administered homologous dsRNA (with perfect sequence identity to the target species) or heterologous dsRNA (generated against a related gene of non-identical sequence in a different insect species). For the aphids Acyrthosiphon pisum and Myzus persicae, significantly reduced NUC expression was obtained with the homologous but not heterologous dsRNA at 0.2 µg µL−1, despite high dsNUC sequence identity. Follow-up experiments demonstrated significantly reduced expression of NUC genes in the whitefly Bemisia tabaci and mealybug Planococcus maritimus administered homologous dsNUCs, but not heterologous aphid dsNUCs. Our demonstration of inefficient expression knockdown by heterologous dsRNA in these insects suggests that maximal dsRNA sequence identity is required for RNAi targeting of related pest species, and that heterologous dsRNAs at appropriate concentrations may not be a major risk to non-target sap-feeding hemipterans.

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Section: Discussionmentioning

confidence: 99%

Non-Target Effects of dsRNA Molecules in Hemipteran Insects

Arora

Chung

Douglas

2021

Genes

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“…Since RNAi is a sequence-based mechanism, any dsRNA with sufficient homology to an arthropod mRNA may trigger RNAi in a non-targeted manner. Therefore, dsRNA-mediated approaches under development should be accompanied with ecotoxicological studies to identify any effects in non-target organisms [27][28][29][30]. Castellanos et al [31] reported that the combined use of RNAi-mediated gene silencing against the Neotropical brown stink bug Euschistus heros (F.) (Hemiptera, Pentatomidae), together with eggs of the parasitoid Telenomus podisi Ashmead (Hymenoptera, Scelionidae), proved to be a feasible approach.…”

Section: Introductionmentioning

confidence: 99%

dsRNA-Mediated Pest Management of Tuta absoluta Is Compatible with Its Biological Control Agent Nesidiocoris tenuis

Sarmah

Kaldis

Taning

et al. 2021

Insects

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RNAi-mediated insect pest management has recently shown promising results against the most serious pest of tomato, the tomato leafminer, Tuta absoluta. This study aimed to investigate whether dsRNA (dsTa-αCOP) designed to target the T. absoluta-αCOP gene could cause adverse effects to its biocontrol agent, the mirid predator, Nesidiocoris tenuis. Oral exposure of N. tenuis to dsRNA (dsNt-αCOP) designed to target N. tenuis-αCOP resulted in a 61%, 67% and 55% reduction in its transcript level in comparison to the sucrose, dsGFP and dsTa-αCOP treatments, respectively. In addition, significantly higher mortality of 57% was recorded in dsNt-αCOP-treated N. tenuis when compared to the sucrose (7%), dsGFP (10%) and dsTa-αCOP (10%) treatments. Moreover, the predation rate of ~33–39 Ephestia kuehniella eggs per N. tenuis adult dramatically reduced to almost half in the surviving dsNt-αCOP-treated N. tenuis. This worst-case exposure scenario confirmed for the first time that the RNAi machinery is functional in this species and that the risk of exposure through the oral route is possible. In contrast, dsTa-αCOP did not cause any sub-lethal effects to N. tenuis upon oral exposure. Oral exposure of T. absoluta to dsTa-αCOP resulted in 50% mortality. In the context of a biosafety risk assessment of RNAi-mediated insect management, investigating the effects on non-target organisms is essential in order to include this method as part of an integrated pest management strategy. Based on our laboratory assays, RNAi-mediated control is compatible with the biological control of T. absoluta by its natural enemy N. tenuis, adding the RNAi approach in the armoire of integrated pest management of T. absoluta.

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“…The assessment of the scientific arguments provided in TB-134 does not provide sufficient justification to support the re-examination of the EFSA GMO Panel conclusions Papadopoulou et al (2020) and summarised in EFSA (2020a). To EFSA's knowledge, at the international level, no dedicated guidelines have been developed for the risk assessment and regulation of RNAi-based GMPs, confirming that existing science-based risk assessment approaches for GMPs are generally considered also suitable for RNAi-based GMPs.…”

Section: Efsa Conclusion On Tb-134mentioning

confidence: 93%

Scientific assistance on the internal review under Regulation (EC) No 1367/2006 of the Commission Implementing Decisions on genetically modified soybean MON 87751 x MON 87701 × MON 87708 x MON 89788, maize MON 87427 × MON 87460 × MON 89034 × MIR162 × NK603 and subcombinations and maize MON 87427 × MON 89034 × MIR162 × MON 87411 and subcombinations

Neri¹,

Afonso²,

Sanctis³

et al. 2021

EFSA Supporting Publications

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Following a request of the European Commission, the European Food Safety Authority (EFSA) reviewed the scientific arguments raised by the non-governmental organisation Testbiotech requesting the review of Commission Implementing Decisions (EU) No 2021/66, 2021/61 and 2021/65 , authorising the placing on the market of products containing, consisting of or produced from the four-event stack soybean MON 87751 × MON 87701 × MON 87708 × MON 89788 (application EFSA-GMO-NL-2016-128), the five-event stack maize MON 87427 × MON 87460 × MON 89034 × MIR162 × NK603 and its subcombinations (application EFSA-GMO-NL-2016-134) and the four-event stack maize MON 87427 × MON 89034 × MIR162 × MON 87411 and its subcombinations (application EFSA- GMO-NL-2017-144). In relation to the four-event stack soybean and the five-event stack maize, Testbiotech argued that the risk assessment performed by the EFSA Scientific Panel on Genetically Modified Organisms (EFSA GMO Panel) is insufficient as regards molecular characterisation, comparative analyses, toxicological and allergenicity assessment and environmental assessment. For the four-event stack maize, Testbiotech claims that the risk assessment performed by the EFSA GMO Panel is inadequate considering the general knowledge gaps in the assessment of RNAi-based GM plants. EFSA's assessment focuses on scientific elements and does not cover legal aspects, as they are not in EFSA's remit and not in the frame of the mandate received from the EC. The assessment of the scientific arguments provided in the technical background of the three requests does not give enough justification to support the re-examination of the EFSA GMO Panel risk assessment conclusions and risk management recommendations.

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Risk Assessment Considerations for Genetically Modified RNAi Plants: EFSA’s Activities and Perspective

Cited by 39 publications

References 45 publications

Non-Target Effects of dsRNA Molecules in Hemipteran Insects

Non-Target Effects of dsRNA Molecules in Hemipteran Insects

dsRNA-Mediated Pest Management of Tuta absoluta Is Compatible with Its Biological Control Agent Nesidiocoris tenuis

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