Scientific References

References about the unintended consequences of gene editing

References about the unintended consequences of gene editing

MUTATIONS CAN AFFECT THE FUNCTIONING OF MANY GENES

UNINTENDED MUTATIONS

Mutations can affect the functioning of many genes, with unknown consequences for biochemical composition and function. In the case of plants, this can result in altered levels of allergens and toxins. Most of the DNA damage described below is outside the control of genetic engineers, as it is a consequence of the cell’s DNA repair machinery (after the gene-editing tool creates cuts in the...
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Jun 04, 2022

UNINTENDED MUTATIONS

Mutations can affect the functioning of many genes, with unknown consequences for biochemical composition and function. In the case of plants, this can result in altered levels of allergens and toxins. Most of the DNA damage described below is outside the control of genetic engineers, as it is a consequence of the cell’s DNA repair machinery (after the gene-editing tool creates cuts in the...
Jun 04, 2022
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CHROMOSOMAL

An article in Nature entitled, “CRISPR gene editing in human embryos wreaks chromosomal mayhem,” describes three separate studies, which showed that t here were “DNA rearrangements and large deletions of several thousand DNA letters,” and “large segments of the chromosome — and sometimes the entire chromosome,” were lost. Nature reported that many of the findings “can be missed by standard assessment methods,” and that the results “heighten safety concerns about heritable genome editing.”

OFF-TARGET

Gene-editing tools, especially CRISPR, are prone to causing mutations (damage) to the organism’s DNA at locations other than the intended edit site (off-target mutations.)

Wolt JD et al (2016). The Plant Genome 9(3):10.3835/plantgenome2016.05.0047.
https://pubmed.ncbi.nlm.nih.gov/28712498/

Zhu C et al (2017). Trends in Plant Science 22(1):38–52.
https://pubmed.ncbi.nlm.nih.gov/27645899/

Genomic rearrangement resulting from shattering of chromosomes (chromothripsis) at on-target gene editing sites

Michael Leibowitz talks about CRISPR gene editing for gene therapy applications can cause massive damage to chromosomes. The phenomenon is known as chromothripsis. The fact that the damage occurs “on-target” – at the intended edit site – means that any attempts to target the CRISPR gene editing more precisely will not solve this problem. Leibowitz ML et al (2021). Chromothripsis as an on-target...
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Large DNA deletions and rearrangements at both off-target and on-target sites

Large deletions and rearrangements of the plant’s genome, which can involve thousands of base units of DNA, have been observed following CRISPR gene editing. Biswas S et al (2020). Investigation of CRISPR/Cas9-induced SD1 rice mutants highlights the importance of molecular characterization in plant molecular breeding. Journal of Genetics and Genomics. May 21. doi:10.1016/j.jgg.2020.04.004....
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Gene-editing process-induced mutations

The action of the gene editing tools is not the only cause of genome disruption. The gene editing process, taken as a whole (including plant tissue culture and GM transformation procedure), induces hundreds of unintended mutations throughout the genome of the plant. This can affect multiple gene functions with unknown consequences to protein biochemistry and metabolic activity. Tang X Tang X et...
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Creation of new gene sequences leads to new RNA and protein products

Alteration of the genetic code of the targeted gene can produce mutant forms of the protein it encodes for, new RNA, and new protein products. These outcomes can lead to changes in the plant’s biochemistry and the possible production of novel allergens and toxins. Mou H. This study in human cells unexpectedly found large deletions resulting from single CRISPR-induced cuts, in some cases in...
LEARN MORE HERE

Insertion of foreign and contaminating DNA into genome at editing sites

Following creation of a double-strand DNA break by the CRISPR gene-editing tool, the repair can unexpectedly include the insertion and rejoining of the broken DNA ends of the recombination template DNA used, or the insertion of contaminating DNA present in materials used in the plant tissue culture. This insertion of extraneous DNA in the genome of the plant, which can take place at off-target...
LEARN MORE HERE

Genomic rearrangement resulting from shattering of chromosomes (chromothripsis) at on-target gene editing sites

Michael Leibowitz talks about CRISPR gene editing for gene therapy applications can cause massive damage to chromosomes. The phenomenon is known as chromothripsis. The fact that the damage occurs “on-target” – at the intended edit site – means that any attempts to target the CRISPR gene editing more precisely will not solve this problem. Leibowitz ML et al (2021). Chromothripsis as an on-target...
LEARN MORE HERE

Large DNA deletions and rearrangements at both off-target and on-target sites

Large deletions and rearrangements of the plant’s genome, which can involve thousands of base units of DNA, have been observed following CRISPR gene editing. Biswas S et al (2020). Investigation of CRISPR/Cas9-induced SD1 rice mutants highlights the importance of molecular characterization in plant molecular breeding. Journal of Genetics and Genomics. May 21. doi:10.1016/j.jgg.2020.04.004....
LEARN MORE HERE

Gene-editing process-induced mutations

The action of the gene editing tools is not the only cause of genome disruption. The gene editing process, taken as a whole (including plant tissue culture and GM transformation procedure), induces hundreds of unintended mutations throughout the genome of the plant. This can affect multiple gene functions with unknown consequences to protein biochemistry and metabolic activity. Tang X Tang X et...
LEARN MORE HERE

Creation of new gene sequences leads to new RNA and protein products

Alteration of the genetic code of the targeted gene can produce mutant forms of the protein it encodes for, new RNA, and new protein products. These outcomes can lead to changes in the plant’s biochemistry and the possible production of novel allergens and toxins. Mou H. This study in human cells unexpectedly found large deletions resulting from single CRISPR-induced cuts, in some cases in...
LEARN MORE HERE

Insertion of foreign and contaminating DNA into genome at editing sites

Following creation of a double-strand DNA break by the CRISPR gene-editing tool, the repair can unexpectedly include the insertion and rejoining of the broken DNA ends of the recombination template DNA used, or the insertion of contaminating DNA present in materials used in the plant tissue culture. This insertion of extraneous DNA in the genome of the plant, which can take place at off-target...
LEARN MORE HERE

NEED FOR REGULATIONS

Unintended genomic outcomes in current and next generation GM techniques

Third World Network summarises the findings of an important new study

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.

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New GM plants do not have a history of safe use and should not be exempted from biosafety assessments

Eckerstorfer MF et al (2021). Biosafety of genome editing applications in plant breeding: Considerations for a focused case-specific risk assessment in the EU. BioTech 2021, 10(3), 10 https://doi.org/10.3390/biotech10030010 This important review of the safety of gene-edited GM plants for health and the environment was authored by a group of scientists working for national government regulatory agencies in EU member states and Switzerland. The review discusses how to assess the risk and safety of gene-edited GM plants in light of the European Food Safety Authority (EFSA) opinions on this topic. It challenges EFSA to improve its guidance on the risk assessment of gene-edited GM plants and points out some misconceptions on the part of EFSA, certain scientists, and lobbyists who want to weaken regulations on gene-edited plants.

Other reports on the need for regulation of gene editing include:

Not enough is known about the off-target modifications brought about by some forms of gene-editing to assume safety

If gene-edited plants can, as claimed, be developed at greater speed, that can mean HIGHER risk.

Kawall K: The generic risks and the potential of SDN-1 applications in crop plants. https://www.mdpi.com/2223-7747/10/11/2259/htm

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