USDA, KEITH WELLERGenome-editing technologies—including zinc finger nuclease (ZFN), transcription activator-like effector nuclease (TALEN), and CRISPR/Cas tools—have facilitated various gene modifications even in higher organisms. Meanwhile, advanced genetic engineering raises a worldwide regulatory issue by creating indistinct boundaries in genetically modified organism (GMO) regulations because, without introducing new genetic material, genome editing can be used to make modifications similar to naturally occurring mutations. To encourage public discussion on the regulatory issue, my colleagues and I last year presented a general drawing of the complicated regulatory issue in Trends in Biotechnology. Now, in an article published in Trends in Plant Science this week (February 25), Motoko Araki and I focus on genome-edited crops in the context of global GMO regulation.
First, we analyzed 13 research articles of genetically modified varieties of barley, rice, sweet orange, wheat, soybean, corn, and tomato. We found that rice was the most frequently modified of all major crops. The most common modification types of all crops studied were mutations with a few bases deleted or inserted (indels), resulting in modified crops that resemble naturally occurring mutants. The genes targeted for mutation had been selected for the purposes such as introducing herbicide resistance, increasing nutritional value, and changing flavor. Although gene modification efficiency varies between target genes, in some cases, it can reach up to 40 percent. Genome editing may induce off-target mutations in plant genomes, which might be associated with health and environmental risks. However, less than half of the articles we studied (five of 13) investigated the occurrence of off-target mutations. Although genome-editing technologies are rapidly advancing in terms of the specificity and efficiency, off-target effects should be more comprehensively investigated in each plant.
Although genome editing can be applied to crop breeding for various purposes, indel mutants, which are not captured by most GMO regulations, were frequently produced in the research we analyzed. Appropriate regulatory response is essential to plant breeding by genome editing.
We further developed regulatory models linking with current GMO regulations. We categorized various plant mutants produced by genome editing according to gene modification methods and functional changes, and then mapped them in order of relevance to the current product-based GMO regulations. Thus, a regulatory concept with four potential regulatory lines was developed (see figure below).
To achieve social acceptance of genome-edited crops, it is also important to consider how to label food containing ingredients derived from them. Recently, the civil movement “Right to Know” has demanded the labelling of GMOs. A regulatory agency is likely to encounter difficulties in identifying an indel crop mutant when inspecting foods containing such crops. If consumers want to know whether food contains ingredients of genome-edited crops, one possible solution is the introduction of an additional DNA tag in such plants. This solution can be an option to enhance the social acceptance as long as the DNA tag is found to incur no health and environmental risks.
Most of the plant mutants in the analyzed reports may be outside the current GMO regulations. Although the selection of a regulatory line may vary from country to country, we propose that the most stringent regulation should be initially adopted and gradually relaxed for cautious integration of genome-edited crops into society. We also urge careful consideration of labelling of food containing genome-edited crops.
Worldwide, regulatory response to genome editing have been delayed. We hope that our analysis provides a basis for discussion on global regulations and stimulates public discussion on foods containing genome-edited crops.
TRENDS IN PLANT SCIENCE, ARAKI AND ISHII
Tetsuya Ishii is an associate professor at Hokkaido University’s Office of Health and Safety.