THIRD WORLD NETWORK BIOSAFETY INFORMATION SERVICE
Dear Friends and Colleagues
Genome Editing Found to Cause Numerous Genomic Irregularities
Genome editing techniques, especially CRISPR/Cas, are increasingly being used to achieve agriculturally relevant novel traits and/or genetic combinations in both plants and animals, with commercial growing or rearing so far limited to the U.S. and Canada. However, there are numerous reports of unintended effects arising from genome editing, summarised under the term ‘genomic irregularities’.
A recent scientific paper (Item 1) shows that genome editing can cause genomic irregularities in the resultant GMOs, even if genes are not inserted, or inserted only transiently. The paper provides a systematic overview of such unintended effects, including risks associated with the intended biological characteristics generated through genome editing. Errors triggered by the process are found ‘off-target’ at sites in the genome other than the target site, and also in the region of the target site, ‘on target’ (Item 2). These effects include, for example, the misreading of DNA which can lead to changes in protein composition, unintended insertion of DNA sequences, deletions and rearrangements of DNA. Moreover, as genome-editing of plants frequently makes use of older genetic engineering techniques, any genetic errors resulting from the application of such techniques also need be taken into account.
The authors underscore the need for a process-oriented risk assessment. They recommend expansion of the molecular characterisation element of the risk assessment that enables analysis for off-target effects, unintended on-target effects and effects on genomic regulation. Furthermore, detection of any downstream effects and genomic irregularities will require development and standardisation of ‘omics’ technologies. The application of such technologies would also improve the risk assessment of first-generation GMOs.
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Third World Network
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Item 1
BROADENING THE GMO RISK ASSESSMENT IN THE EU FOR GENOME EDITING TECHNOLOGIES IN AGRICULTURE
Kawall, K., Cotter, J. & Then, C.
Environ Sci Eur 32, 106 (2020)
11 August 2020
https://doi.org/10.1186/s12302-020-00361-2
https://enveurope.springeropen.com/articles/10.1186/s12302-020-00361-2#citeas
Abstract
Genome editing techniques, especially the CRISPR/Cas technology, increase the possibilities and the speed of altering genetic material in organisms. So-called genome editing is increasingly being used to achieve agriculturally relevant novel traits and/or genetic combinations in both plants and animals, although predominantly as proof of concept studies, with commercial growing or rearing so far limited to the U.S. and Canada. However, there are numerous reports of unintended effects such as off-target effects, unintended on-target effects and other unintended consequences arising from genome editing, summarised under the term genomic irregularities. Despite this, the searching for genomic irregularities is far from routine in these studies and protocols vary widely, particularly for off-target effects, leading to differences in the efficacy of detection of off-target effects. Here, we describe the range of specific unintended effects associated with genome editing. We examine the considerable possibilities to change the genome of plants and animals with SDN-1 and SDN-2 genome editing (i.e. without the insertion of genes conferring the novel trait) and show that genome editing techniques are able to produce a broad spectrum of novel traits that, thus far, were not possible to be obtained using conventional breeding techniques. We consider that the current EU risk assessment guidance for GMOs requires revision and broadening to capture all potential genomic irregularities arising from genome editing and suggest additional tools to assist the risk assessment of genome-edited plants and animals for the environment and food/animal feed in the EU.
Conclusions
We have shown here that genome editing can cause genomic irregularities in the resultant GMOs, even if genes are not inserted, or inserted only transiently. Whilst molecular characterisation requirements in the current EU risk assessment guidelines for GMOs may capture many of these irregularities, some may be specific to genome editing, e.g. unintentional integration of plasmid components or large deletions at genomic locations distant to the target side and elude detection under current guidelines.
Therefore, the current EU risk assessment guidance for GMOs requires revision and expansion. Expansion of the molecular characterisation element of the risk assessment that enables analysis for off-target effects, unintended on-target effects and effects on genomic regulation is needed. Detection of any downstream effects and genomic irregularities will require development and standardisation of ‘omics technologies. Applications of such technologies would also improve the risk assessment of first-generation GMOs. The EU risk assessment for genome-edited organisms will also require consideration of a broader range of crop traits than first-generation GMOs. For some traits of genome-edited crops and animals there may be a complete lack of experience in assessing risks to the environment, food and animal feed. Further developments in technologies to assist detection of off-target effects and unintended on-target effects caused by genome editing are needed, as are developments in technologies to detect the resultant GMOs. However, the technological problems are not insurmountable, and techniques can be developed if there is political will to do so.
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Item 2
NEW GENETIC ENGINEERING TECHNIQUES ASSOCIATED WITH NUMEROUS RISKS
New scientific paper demonstrates the need for process-oriented risk assessment
Media Release
Testbiotech
12 August 2020
https://www.testbiotech.org/sites/default/files/Risk%20of%20genome%20editing.pdf
A new scientific paper published in the Environmental Sciences Europe journal gives an overview of the risks associated with genome editing procedures (new genetic engineering) for plants and animals. The risks are not only restricted to a wide range of unintended effects that can be triggered by the process of genome editing. There are also risks associated with the intended biological characteristics generated through genome editing.
Genome editing techniques, in particular those using the CRISPR/Cas ‘gene scissors’, increase the possibilities and speed with which the genomes of plants and animals can be altered. It does not matter whether additional genes are introduced into the genome or not. Small genetic modifications are often performed in combination and can cause significant changes in metabolic pathways and plant composition. The study concludes that the novel, intended properties must be thoroughly tested, even if no additional genes are inserted.
Furthermore, the study provides a systematic overview of unintended effects that are specific to the use of genome editing. Errors triggered by the process are found ‘off-target’ at sites in the genome other than the target site, and also in the region of the target site, ‘on target’. These effects include, for example, the misreading of DNA which can lead to changes in protein composition, unintended insertion of DNA sequences, deletions and rearrangements of DNA. Again, all these genetic errors can arise whether or not genes are inserted.
The new study found that genome-editing of plants frequently makes use of older genetic engineering techniques, and argues that any genetic errors resulting from the application of these older techniques also need be taken into account. The background: in order to be able to use the new ‘gene scissors’, they often need to be introduced into the cells using old genetic engineering techniques in a first step (e.g. by using the so-called ‘gene gun’).
The results published in the paper are in stark contrast to the European Food Safety Authority (EFSA) assessments, which were recently published and put up for public consultation. Similarly to the biotech industry, EFSA comes to the conclusion that the new genetic engineering processes are not associated with new risks. This paper shows that the opinion of EFSA is not consistent with the facts.
Contact: Christoph Then, Tel +49 151 54638040, info@testbiotech.org
Further information:
The publication: https://enveurope.springeropen.com/articles/10.1186/s12302-020-00361-2
EFSA consultation: http://www.efsa.europa.eu/en/consultations/call/public-consultation-applicability-efsa-opinion-site-directedTestbiotech comment on EFSA consultation: https://www.testbiotech.org/node/2593