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Will Plant Genome Editing Benefit Us? – Hopes and Challenges of Genome-Edited Crops as Seen in Review Papers from Around the World –

2024.05.03

The Birth of the Genome-Edited Tomato

Japan’s inaugural genome-edited food is a tomato, a high-value-added crop resulting from collaborative research between the University of Tsukuba and Sanatech Seed Co. Ltd., a startup affiliated with the university. Dubbed “Sicilian Rouge High Gaba,” this tomato received notification approval from the Ministry of Health, Labor, and Welfare in December 2020 [1].

One reason genome-edited foods have garnered attention is the implementation of the notification system [2], initiated in October 2019. Unlike genetically modified foods, which integrate genes from foreign species, genome-edited foods target trait alterations by selectively knocking out specific genes within the genome.

The Ministry of Health, Labor and Welfare suggests the following. ‘If the level of edited off-target genetic mutation is difficult to judge compared to mutations that could also occur stochastically in nature, and if the transgene does not remain, it is reasonable to treat it differently from GM food.’

Starting with Sanatech Seed tomatoes, the future of genome-edited foods on our tables is not far off. Eventually, we may be eating genome-edited foods as a matter of course (or even without knowing that they are genome-edited).

Issues in Plant Genome Editing as Seen in Review Papers

① The need to reconsider regulations

We commence with a review paper entitled “Gene Editing in Plants: Progress and Challenges” authored by Yanfeni Mao and co-authors [3], which was submitted to the National Science Review in January 2019. Yanfeni et al observe that genome editing research in plants is steadily advancing, thanks to the emergence of CRISPR/Cas9 and CRISPR/Cas12a.

Simultaneously, several obstacles hinder the utilization of genome editing in crop breeding. Foremost among these is the ongoing discourse regarding the classification of genome-edited crops as genetically modified organisms (GMOs). In Japan, as previously noted, regulatory measures have been established since October 2019, delineating standards for genome-edited crops and GMOs, thereby distinguishing between the two. Similar determinations have been made in the United States, where genomic research is flourishing. Conversely, in Europe, genome-edited crops face stringent regulations as they are equated with GMOs. Furthermore, disparities in regional attitudes frequently result in import and export limitations, posing research impediments. Given that numerous crops are traded internationally, these restrictions can wield considerable influence.

Yanfeni argues that concerns about treating genome-edited crops are unfounded and that regulations should be re-examined. This is because most genetic mutations induced by CRISPR are small insertions or deletions (indels), rather than large insertions or rearrangements of gene fragments. These mutations are often found in plants grown under natural conditions. They argue that genome-edited crops should be treated like conventional crops because they are common in plants and can be induced on a large scale using radiation or chemical mutagens, just as Japan has done.

Another important issue to consider, in addition to regulatory concerns, is whether society will accept genome-edited crops. Despite the legality of genome editing, the mere mention of it often evokes unfounded fears of science fiction scenarios. While genome-edited foods are a technical revolution, their acceptance by the general public is crucial for their success. Communicating the benefits of genome-edited foods to non-scientific audiences will be a key challenge in the future.

②Off-target Effects

The following technical challenge concerns off-target effects. These effects occur when the gRNA sequence mismatch tolerance in CRISPR/Cas9 and other factors cause cleavage of a different target than intended, resulting in irreversible genetic mutations. In recent years, machine learning and deep learning tools have emerged to predict the target gRNA more accurately. However, these tools still face many challenges, and the off-target effect has not been fully resolved.

However, Yanfeni et al claim that off-target effects do not necessarily hurt crops; some off-target effects may lead to mutations that are desirable to us or may not pose any particular problems. In other words, such reproductive stocks should be retained, and only those individuals who have developed undesirable mutations should be eliminated.

The same is detailed in the 2020 paper ‘Plant Genome Editing and the Relevance of Off-Target Changes'[6] by Nathaniel Graham et al.

According to Nathaniel and his colleagues, many plants develop multiple independent reproductive organs within a single organism and thus have a smaller impact on the entire population than the off-target effects that occur in animals. Therefore, it is suggested that selecting individual plants with useful phenotypes through proper management can minimize the impact of off-target effects.

However, this claim may be sophistry the issue as these mutations are not always visible. Efforts will continue to develop sequence-finding tools without off-target effects and appropriate CRISPR/Cas vectors.

③ Impact of genome editing on surrounding plants

Finally, let’s consider new problems that may arise from genome editing. Finally, let’s consider new problems that may arise from genome editing. In the article ‘Herbicide Resistance: Another Hot Agronomic Trait for Plant Genome Editing’ by Amjad Hussain and colleagues [7], published in Plants in 2021, The authors suggest that the rise of genome-edited crops using CRISPR/Cas could lead to changes in surrounding weeds during cultivation.

Weeds compete with crops for water and nutrients, which can negatively impact production. Additionally, weeds can serve as parasitic sites for pathogens and insects, which can infect crops and harm native ecosystems. Herbicides are often used to control weeds when cultivating crops. However, non-selective herbicides such as glyphosate and paraquat can also harm the crop.

To address this issue, genome-edited crops that are tolerant to herbicides have been developed in recent years. Research has already been published on the development of herbicide-tolerant crops in over 10 species, including rice, wheat, and watermelon, according to Amjad Hussain. If genome editing of crops can result in herbicide tolerance as a side effect, it may seem like a reasonable approach.

However, the development of herbicide-tolerant crops may lead to increased herbicide use, which can raise costs and reduce effectiveness as weeds become resistant. This creates an ironic situation where genome editing research on herbicide resistance may lead to increased herbicide use and decreased effectiveness.

Although genome editing technology is revolutionary, it poses many challenges. Focusing solely on the advantages can cause problems and may even exacerbate the situation. Therefore, careful consideration and attention are needed to make beneficial use of this technology.

This time based on three review articles, We have introduced three points worth paying attention to. Furthermore, ongoing research on plant genome editing highlights many other issues that need to be resolved as the technology progresses. It is important to maintain interest and discussion on genome-edited foods to improve our lives in the future.

References

[1] 日本経済新聞 「「ゲノム編集食品」国が初承認 トマト流通へ」
[2] 薬事・食品衛生審議会食品衛生分科会 新開発食品調査部会 報告書 「ゲノム編集技術を利用して得られた食品等の食品衛生上の取扱いについて 平成31年3月27日 」
[3] Yanfei Mao, Jose Ramon Botella, Yaoguang Liu, Jian-Kang Zhu, Gene editing in plants: progress and challenges, National Science Review, Volume 6, Issue 3, May 2019, Pages 421–437, https://doi.org/10.1093/nsr/nwz005
[4] Pallarès Masmitjà M, Knödlseder N, Güell M. CRISPR-gRNA Design. Methods Mol Biol. 2019;1961:3-11. doi:10.1007/978-1-4939-9170-9_1
[5] Lin Y, Cradick TJ, Brown MT, et al. CRISPR/Cas9 systems have off-target activity with insertions or deletions between target DNA and guide RNA sequences. Nucleic Acids Res. 2014;42(11):7473-7485. doi:10.1093/nar/gku402
[6] Graham N, Patil GB, Bubeck DM, et al. Plant Genome Editing and the Relevance of Off-Target Changes. Plant Physiol. 2020;183(4):1453-1471. doi:10.1104/pp.19.01194
[7] Zhang, R.; Liu, J.; Chai, Z.; Chen, S.; Bai, Y.; Zong, Y.; Chen, K.; Li, J.; Jiang, L.; Gao, C. Generation of herbicide tolerance traits and a new selectable marker in wheat using base editing. Nat. Plants 2019, 5, 480–485.