TWN Info Service on Biosafety
2 February 2023
Third World Network
www.twn.my
Dear Friends and Colleagues
Unintended Genomic Outcomes in Current and Next Generation GM Techniques
Classical genetic engineering and new genome editing techniques, especially the CRISPR/Cas technology, increase the possibilities for modifying the genetic material in organisms. Legitimate safety concerns arise from the unintended genetic modifications that have been reported as side-effects of such techniques.
A recent paper systematically reviewed the scientific literature for studies that have investigated unintended genomic alterations in plants modified. It showed a range of impacts of such techniques in host genomes, varying from small nucleotide polymorphisms to large genomic variation. It also revealed a clear lack of detailed information on experimental designs in the publications examined. As unintended outcomes are directly correlated to the type of analytical method used to investigate DNA sequence alterations, most papers might underestimate these effects, due to lack of dedicated testing.
The authors conclude that there is a need to develop frameworks related to proper reporting and dedicated experimental setups as well as for the definition of biological relevance of the generated data. New tools such as third generation sequencing are further needed to enable a comprehensive risk assessment. As new technologies are constantly evolving, a more thorough examination of prospective analytical methods should be conducted in the future. This will provide regulators working in the field of genetically modified and gene-edited organisms with valuable information on the ability to detect and identify genomic interventions.
We reproduce below the Abstract and Conclusions of the paper.
With best wishes,
Third World Network
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UNINTENDED GENOMIC OUTCOMES IN CURRENT AND NEXT GENERATION GM TECHNIQUES: A SYSTEMATIC REVIEW
Chu, P., & Agapito-Tenfen, S. Z. (2022).
Plants, 11(21), 2997
https://doi.org/10.3390/plants11212997
https://www.mdpi.com/2223-7747/11/21/2997
7 November 2022
Abstract
Classical genetic engineering and new genome editing techniques, especially the CRISPR/Cas technology, increase the possibilities for modifying the genetic material in organisms. These technologies have the potential to provide novel agricultural traits, including modified microorganisms and environmental applications. However, legitimate safety concerns arise from the unintended genetic modifications (GM) that have been reported as side-effects of such techniques. Here, we systematically review the scientific literature for studies that have investigated unintended genomic alterations in plants modified by the following GM techniques: Agrobacterium tumefaciens-mediated gene transfer, biolistic bombardment, and CRISPR-Cas9 delivered via Agrobacterium-mediated gene transfer (DNA-based), biolistic bombardment (DNA-based) and as ribonucleoprotein complexes (RNPs). The results of our literature review show that the impact of such techniques in host genomes varies from small nucleotide polymorphisms to large genomic variation, such as segmental duplication, chromosome truncation, trisomy, chromothripsis, breakage fusion bridge, including large rearrangements of DNA vector-backbone sequences. We have also reviewed the type of analytical method applied to investigate the genomic alterations and found that only five articles used whole genome sequencing in their analysis methods. In addition, larger structural variations detected in some studies would not be possible without long-read sequencing strategies, which shows a potential underestimation of such effects in the literature. As new technologies are constantly evolving, a more thorough examination of prospective analytical methods should be conducted in the future. This will provide regulators working in the field of genetically modified and gene-edited organisms with valuable information on the ability to detect and identify genomic interventions.
Conclusions, and Future Directions
This systematic review revealed a clear lack of detailed information on experimental designs in the publications examined, which posed a limitation to our meta-analysis. In the context of unintended DNA alterations, we found a range of different sequence rearrangements ranging from the introduction of small INDELs to long sequence chromosomal duplications. The literature shows that the unintended outcomes are directly correlated to the type of analytical method used to investigate DNA sequence alterations and that most papers might have an underestimation of these effects due to lack of dedicated testing.
We found no guidelines or methodological trends regarding experimental design, choice of analytical method and statistical analysis. Therefore, for efficient regulatory implementation of such testing, there is a need to develop frameworks related to proper reporting and dedicated experimental setups. Most importantly, there is a need for a framework for the definition of biological relevance of the generated data. We have observed the same pattern when we investigated alterations in the proteomic and metabolomic profile analyses of GM plants. Nevertheless, the lack of harmonized methods seems to be due to the rapid progress of omics technologies rather than inconsistent reporting. This can be observed even from the short window of five years-old papers analyzed in this study.
In summary, we conclude that new genomic techniques, such as sequencing techniques, are suitable tools to comprehensively screen for alterations in genetically modified plants due to their high throughput and untargeted nature. In light of the speed of development of new GMOs, new tools such as third generation sequencing are needed to enable a comprehensive risk assessment.