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Genome Editing

Genome editing, also called gene editing, techniques are a type of genetic engineering, resulting in the creation of genetically modified organisms (GMOs). Genome editing is a collection of techniques that alter the genetic material of genetic material of plants, animals and microbes. The aim is to insert, delete or otherwise change a DNA sequence at a specific, targeted site or sites in the genome. These new genetic engineering techniques raise many of the same risk questions as earlier techniques of genetic engineering, and raise the same environmental, social, economic and ethical concerns.report cover

The new techniques can make it easier and faster to genetically engineer a wider range of organisms, for more purposes. They are powerful research tools that are being used to better understand gene function and, in particular, to genetically modify mice and other research animals to study human diseases. They are also being used to experiment with creating new GM crop plants and farm animals. The biotechnology industry argues that genome editing should not be classified as genetic modification, and should not be regulated or labelled.

CBAN Report: Genome Editing in Food and Farming: Risks and Unexpected Consequences, July 2020

Updates

June 2020: A suite of new studies has found large, unwanted changes to the genome at or near the target site (on-target effects). See CRISPR gene editing in human embryos wreaks chromosomal mayhem: Three studies showing large DNA deletions and reshuffling heighten safety concerns about heritable genome editing, Heidi Ledford, June 25, 2020, Nature (news) 583: 17-18.

June 2020: CBAN’s Letter to the Editor, “Non-GMO claims cause confusion” in The Western Producer, in response to the article “Transgenic crops: end of an era,” (June 4).

Introduction

Genome editing, also called gene editing, is a term used to describe a collection of new techniques that alter the genetic material (usually DNA) of plants, animals and microbes. In general, these techniques consist of different types of DNA “editing” systems that aim to insert, delete or otherwise change a DNA sequence at specific, targeted sites in the genome. The organism’s genetic material is changed, not through the breeding process, but directly and artificially by humans, making these techniques a type of genetic engineering, resulting in the creation of genetically modified organisms (GMOs).

Genome editing systems are comprised of molecular components that are programmed to make changes (perform “edits”) at a target location in the genome. The most frequently used genome editing technique is CRISPR-Cas9 or CRISPR, but other techniques follow similar principles

Claims that these technologies are safer than other GM techniques are unproven. Each gene editing technique each bring their own set of risks and uncertainties. Whilst many of these are the same as with older genetic engineering techniques, there are also serious additional concerns. There is a strong scientific case for classifying all these techniques as genetic engineering (genetic modification or GM) and regulating their use with as much rigour as previous and current GM techniques.

The term “editing” implies a level of precision that is not currently, and may never be possible. It suggests the ability to rewrite the genetic code and to simply cut and paste DNA but, in reality, the results are still determined by processes in the organism that we neither fully understand nor control.

Gene editing can more efficiently target sites in the genome but the enzymes used in gene editing have been shown to cut DNA in the wrong spots and create off-target mutations. After a cut is made, the cell’s DNA repair mechanisms are in control of what happens next for the organism. The results can be alterations – such as deletions, insertions, and rearrangements – at the intended site, but also at unintended, off-target sites.

Precise edits, even if possible, do not necessarily yield precise outcomes. Even a simple genetic “tweak” can have wide-ranging effects on an organism’s genome.

“In general, greater precision at the molecular level does not directly result in greater safety or higher success rates in plant development.” – Testbiotech (2020), Overview of genome editing applications using SDN-1 and SDN-2 in regard to EU regulatory issues

Click here to download CBAN’s Introduction to Genome Editing in Food and Farming, July 2020.

Unexpected effects

Any attempt to engineer genomes with such invasive methods can cause unexpected and unpredictable effects. Genome editing can cause genetic errors, including “off-target” effects in the genome, unintended “on-target” effects, interference with gene regulation, and intended and unintended insertion of DNA. These genetic errors are important because they can lead to unexpected and unpredictable effects in the resultant genome-edited organisms, that could be important for food and environmental safety.

Unexpected large deletions or rearrangements of DNA can take place at the intended editing site or elsewhere, and can disrupt the function of non-target genes. Unwanted changes may slip by undetected. Even the intended alteration can inadvertently alter other important genes, causing changes in chemistry or protein production that can be important for food and environmental safety. Genome editing may also have unintended impacts on an organism’s ability to express or suppress other genes. The orchestration of gene function in an organism is part of a complex regulatory network that is poorly understood.

For an overview of the genetic errors that can be caused by genome editing processes, see CBAN’s report Genome Editing in Food and Farming: Risks and Unexpected Consequences, July 2020.

Case Study: Genome-Edited Hornless Cows

In 2020, scientists at the US Food and Drug Administration (FDA) reported errors in the genome of cows that were genetically engineered to not grow horns. The genome edited hornless cows had been held up as a positive example of the power and ease of genome editing, and discussed as a demonstration of why genome-edited animals do not need to be regulated. However, the case of the hornless cows shows the potential for errors in the genome editing process, and the need for independent safety assessment.

The dairy cows were genome-edited to be hornless (polled), to eliminate the practice of manually dehorning cows. Two cows were developed by university researchers in collaboration with the U.S. company Recombinetics. The developers reported that they were created without foreign genes and “our animals are free of off-target effects”. However, in 2019, researchers at the U.S. Food and Drug Administration (FDA) found unexpected foreign DNA in the cows (on-target effects).

Read the full story (page 12-13) in CBAN’s new report: Genome Editing in Food and Farming: Risks and Unexpected Consequences.

  • Read the paper Template plasmid integration in germline genome-edited cattle, Alexis L. Norris et al, July 2019: “We analyzed publicly available whole genome sequencing data from cattle which were germline genome-edited to introduce polledness. Our analysis discovered the unintended heterozygous integration of the plasmid and a second copy of the repair template sequence, at the target site. Our finding underscores the importance of employing screening methods suited to reliably detect the unintended integration of plasmids and multiple template copies.”
  • “No matter how “precise” the initial gene-editing event is in terms of location, undesirable outcomes can occur at the intended site stemming from the DNA repair processes that follow the cutting of the DNA by the editing tool. The findings described in the paper by the US FDA scientists are yet another illustration that looking only for off-target effects from a gene-editing procedure is not enough to identify the full spectrum of undesirable outcomes, which can occur even at the intended gene-editing site.” – from Gene-edited hornless cattle: Flaws in the genome overlooked, GMWatch, August 9, 2019.
  • “...the new FDA finding demonstrates is that the Recombinetics gene-edited cattle do contain DNA unnatural to cattle, despite the claims of their developers to the contrary. Thus FDA does have the authority to regulate.” – from FDA Finds Unexpected Antibiotic Resistance Genes in ‘Gene-Edited’ Dehorned Cattle Independent Science News, August 12, 2019.
  • Background on the company Recombinetics from Testbiotech.

Regulation

The biotechnology industry argues that gene editing should not be classified as genetic modification and that the products should be exempt from regulation. Regulation is commonly argued as an expensive and time-consuming obstacle to innovation.

Canada assesses the risks of genetically engineered organisms under regulations for “Novel Foods” and “Plants with Novel Traits”. Most, but not necessarily all, gene edited products will be covered by these regulations because the Canadian government regulates products if they have a “novel” trait, regardless of the process used to make them. The U.S. government is excluding some genome edited products from risk assessment. European regulations for genetically modified organisms cover genome editing: In July 2018, the European Court of Justice ruled that genome-edited organisms (obtained by directed mutagenesis techniques) are genetically modified organisms (GMOs) and therefore subject to existing EU GMO regulations.

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