Advances in identifying GM plants: toward the routine detection of ‘hidden’ and ‘new’ GMOs

Bertheau, Yves

doi:10.19103/as.2021.0097.22

Cited by 4 publications

(8 citation statements)

References 388 publications

(580 reference statements)

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“…The first is the asymmetry problem that arises when trading partners take different approaches. Based on Table 4 , when genome-edited food is exported from countries that adopt Approach 3 (confirmation is required) but do not disclose notification results (e.g., Argentina) or from countries that adopt Approach 4 (companies are allowed to make their own decisions) to countries that adopt Approach 1 or 2, if the exporters do not actively provide information, concerns regarding GM food being distributed under cover (“hidden GMOs”) may spread which disrupts the market ( Bertheau, 2021 ). Some consumer groups are demanding that developers of genome-edited products should develop tracking methods and ensure consumers’ right to choose 28 .…”

Section: Discussion: Cross-regulatory Considerationsmentioning

confidence: 99%

Divergence and convergence in international regulatory policies regarding genome-edited food: How to find a middle ground

Tachikawa

Matsuo

2023

Front. Plant Sci.

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Regulations for organisms and products to which genome-editing technologies are applied are increasing in diversity, with the path-dependent effect of previous regulations for genetically modified organisms. Regulations for genome-editing technologies are a patchwork of international regulations that are difficult to harmonize. However, if the approaches are arranged in chronological order and the overall trend is examined, the regulation of genome-edited organisms and GM food products has recently been trending toward a middle ground which can be characterized as “limited convergence.” There is a trend toward the adoption of two approaches: one that considers GMOs but tries to apply simplified regulations and another that excludes them from the scope of regulations as non-GMOs but requires confirmation. In this paper, we discuss why there is a tendency toward convergence of these two approaches and examine the challenges and implications of these two approaches for the governance of the agricultural and food sectors.

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Section: Discussion: Cross-regulatory Considerationsmentioning

confidence: 99%

Divergence and convergence in international regulatory policies regarding genome-edited food: How to find a middle ground

Tachikawa

Matsuo

2023

Front. Plant Sci.

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“…Methylation status (a change in the physical make-up of the DNA whilst it still retains the same DNA sequence) has been postulated as another way to detect GMOs (16). However, a lack of information regarding the methylation mechanism precludes this, and more research in this area is needed prior to any conclusions being drawn.…”

Section: Other Untargeted Methodsmentioning

confidence: 99%

“…Methods for detection of off-target mutations are subject to the same limitations as any "on-target" mutation: prerequisites being a priori knowledge of the sequence and evidence that the mutation is unique. If evidence is presented that a number of off-target mutations afforded by a genome edit have occurred, some scientists have speculated that there is potential to use these to provide a unique genetic signature/foot-print for a particular PBO (16). However, as off-target mutations are often unlinked to the intended mutation, they may typically segregate out in subsequent generations and their utility as an additional tool for traceability would be lost.…”

Section: Monitoring Off-target Effectsmentioning

confidence: 99%

Literature review on analytical methods for the detection of precision bred products

Burns,

Nixon

2023

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The Genetic Technology (Precision Breeding) Act (England) aims to develop a science-based process for the regulation and authorisation of precision bred organisms (PBOs). PBOs are created by genetic technologies but exhibit changes which could have occurred through traditional processes. This current review, commissioned by the Food Standards Agency (FSA), aims to clarify existing terminologies, explore viable methods for the detection, identification, and quantification of products of precision breeding techniques, address and identify potential solutions to the analytical challenges presented, and provide recommendations for working towards an infrastructure to support detection of precision bred products in the future. The review includes a summary of the terminology in relation to analytical approaches for detection of precision bred products. A harmonised set of terminology contributes towards promoting further understanding of the common terms used in genome editing. A review of the current state of the art of potential methods for the detection, identification and quantification of precision bred products in the UK, has been provided. Parallels are drawn with the evolution of synergistic analytical approaches for the detection of Genetically Modified Organisms (GMOs), where molecular biology techniques are used to detect DNA sequence changes in an organism’s genome. The scope and limitations of targeted and untargeted methods are summarised. Current scientific opinion supports that modern molecular biology techniques (i.e., quantitative real-time Polymerase Chain Reaction (qPCR), digital PCR (dPCR) and Next Generation Sequencing (NGS)) have the technical capability to detect small alterations in an organism’s genome, given specific prerequisites of a priori information on the DNA sequence of interest and of the associated flanking regions. These techniques also provide the best infra-structure for developing potential approaches for detection of PBOs. Should sufficient information be known regarding a sequence alteration and confidence can be attributed to this being specific to a PBO line, then detection, identification and quantification can potentially be achieved. Genome editing and new mutagenesis techniques are umbrella terms, incorporating a plethora of approaches with diverse modes of action and resultant mutational changes. Generalisations regarding techniques and methods for detection for all PBO products are not appropriate, and each genome edited product may have to be assessed on a case-by-case basis. The application of modern molecular biology techniques, in isolation and by targeting just a single alteration, are unlikely to provide unequivocal evidence to the source of that variation, be that as a result of precision breeding or as a result of traditional processes. In specific instances, detection and identification may be technically possible, if enough additional information is available in order to prove that a DNA sequence or sequences are unique to a specific genome edited line (e.g., following certain types of Site-Directed Nucelase-3 (SDN-3) based approaches). The scope, gaps, and limitations associated with traceability of PBO products were examined, to identify current and future challenges. Alongside these, recommendations were made to provide the infrastructure for working towards a toolkit for the design, development and implementation of analytical methods for detection of PBO products. Recognition is given that fully effective methods for PBO detection have yet to be realised, so these recommendations have been made as a tool for progressing the current state-of-the-art for research into such methods. Recommendations for the following five main challenges were identified. Firstly, PBOs submitted for authorisation should be assessed on a case-by-case basis in terms of the extent, type and number of genetic changes, to make an informed decision on the likelihood of a molecular biology method being developed for unequivocal identification of that specific PBO. The second recommendation is that a specialist review be conducted, potentially informed by UK and EU governmental departments, to monitor those PBOs destined for the authorisation process, and actively assess the extent of the genetic variability and mutations, to make an informed decision on the type and complexity of detection methods that need to be developed. This could be further informed as part of the authorisation process and augmented via a publicly available register or database. Thirdly, further specialist research and development, allied with laboratory-based evidence, is required to evaluate the potential of using a weight of evidence approach for the design and development of detection methods for PBOs. This concept centres on using other indicators, aside from the single mutation of interest, to increase the likelihood of providing a unique signature or footprint. This includes consideration of the genetic background, flanking regions, off-target mutations, potential CRISPR/Cas activity, feasibility of heritable epigenetic and epitranscriptomic changes, as well as supplementary material from supplier, origin, pedigree and other documentation. Fourthly, additional work is recommended, evaluating the extent/type/nature of the genetic changes, and assessing the feasibility of applying threshold limits associated with these genetic changes to make any distinction on how they may have occurred. Such a probabilistic approach, supported with bioinformatics, to determine the likelihood of particular changes occurring through genome editing or traditional processes, could facilitate rapid classification and pragmatic labelling of products and organisms containing specific mutations more readily. Finally, several scientific publications on detection of genome edited products have been based on theoretical principles. It is recommended to further qualify these using evidenced based practical experimental work in the laboratory environment. Additional challenges and recommendations regarding the design, development and implementation of potential detection methods were also identified. Modern molecular biology-based techniques, inclusive of qPCR, dPCR, and NGS, in combination with appropriate bioinformatics pipelines, continue to offer the best analytical potential for developing methods for detecting PBOs. dPCR and NGS may offer the best technical potential, but qPCR remains the most practicable option as it is embedded in most analytical laboratories. Traditional screening approaches, similar to those for conventional transgenic GMOs, cannot easily be used for PBOs due to the deficit in common control elements incorporated into the host genome. However, some limited screening may be appropriate for PBOs as part of a triage system, should a priori information be known regarding the sequences of interest. The current deficit of suitable methods to detect and identify PBOs precludes accurate PBO quantification. Development of suitable reference materials to aid in the traceability of PBOs remains an issue, particularly for those PBOs which house on- and off-target mutations which can segregate. Off-target mutations may provide an additional tool to augment methods for detection, but unless these exhibit complete genetic linkage to the sequence of interest, these can also segregate out in resulting generations. Further research should be conducted regarding the likelihood of multiple mutations segregating out in a PBO, to help inform the development of appropriate PBO reference materials, as well as the potential of using off-target mutations as an additional tool for PBO traceability. Whilst recognising the technical challenges of developing and maintaining pan-genomic databases, this report recommends that the UK continues to consider development of such a resource, either as a UK centric version, or ideally through engagement in parallel EU and international activities to better achieve harmonisation and shared responsibilities. Such databases would be an invaluable resource in the design of reliable detection methods, as well as for confirming that a mutation is as a result of genome editing. PBOs and their products show great potential within the agri-food sector, necessitating a science-based analytical framework to support UK legislation, business and consumers. Differentiating between PBOs generated through genome editing compared to organisms which exhibit the same mutational change through traditional processes remains analytically challenging, but a broad set of diagnostic technologies (e.g., qPCR, NGS, dPCR) coupled with pan-genomic databases and bioinformatics approaches may help contribute to filling this analytical gap, and support the safety, transparency, proportionality, traceability and consumer confidence associated with the UK food chain.

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“…(ii) The development of methods for the analytical detection of both new GMOs and genomeedited plants is a dynamic process. Based on sufficient molecular information for genomeedited products, new methods are and will be developed, which may eventually offer the same reliability to detect and identify emerging genome-edited products as the analytical detection methods available for established GMOs [40,41]. (iii) The complexity of many modified genome-edited products (45% of SDN-1, according to Kawall [35]) may simplify the development of analytical methods for the detection and identification of the respective products.…”

Section: Generalized Conclusion Regarding the Detection And Identific...mentioning

confidence: 99%

Recommendations for the Assessment of Potential Environmental Effects of Genome-Editing Applications in Plants in the EU

Eckerstorfer

Dolezel

Engelhard

et al. 2023

Plants

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The current initiative of the European Commission (EC) concerning plants produced using certain new genomic techniques, in particular, targeted mutagenesis and cisgenesis, underlines that a high level of protection for human and animal health and the environment needs to be maintained when using such applications. The current EU biosafety regulation framework ensures a high level of protection with a mandatory environmental risk assessment (ERA) of genetically modified (GM) products prior to the authorization of individual GMOs for environmental release or marketing. However, the guidance available from the European Food Safety Authority (EFSA) for conducting such an ERA is not specific enough regarding the techniques under discussion and needs to be further developed to support the policy goals towards ERA, i.e., a case-by-case assessment approach proportionate to the respective risks, currently put forward by the EC. This review identifies important elements for the case-by-case approach for the ERA that need to be taken into account in the framework for a risk-oriented regulatory approach. We also discuss that the comparison of genome-edited plants with plants developed using conventional breeding methods should be conducted at the level of a scientific case-by-case assessment of individual applications rather than at a general, technology-based level. Our considerations aim to support the development of further specific guidance for the ERA of genome-edited plants.

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Advances in identifying GM plants: toward the routine detection of ‘hidden’ and ‘new’ GMOs

Cited by 4 publications

References 388 publications

Divergence and convergence in international regulatory policies regarding genome-edited food: How to find a middle ground

Divergence and convergence in international regulatory policies regarding genome-edited food: How to find a middle ground

Literature review on analytical methods for the detection of precision bred products

Recommendations for the Assessment of Potential Environmental Effects of Genome-Editing Applications in Plants in the EU

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