An EU Perspective on Biosafety Considerations for Plants Developed by Genome Editing and Other New Genetic Modification Techniques (nGMs)

Abstract

The question whether new genetic modification techniques (nGM) in plant development might result in non-negligible negative effects for the environment and/or health is significant for the discussion concerning their regulation. However, current knowledge to address this issue is limited for most nGMs, particularly for recently developed nGMs, like genome editing, and their newly emerging variations, e.g., base editing. This leads to uncertainties regarding the risk/safety-status of plants which are developed with a broad range of different nGMs, especially genome editing, and other nGMs such as cisgenesis, transgrafting, haploid induction or reverse breeding. A literature survey was conducted to identify plants developed by nGMs which are relevant for future agricultural use. Such nGM plants were analyzed for hazards associated either (i) with their developed traits and their use or (ii) with unintended changes resulting from the nGMs or other methods applied during breeding. Several traits are likely to become particularly relevant in the future for nGM plants, namely herbicide resistance (HR), resistance to different plant pathogens as well as modified composition, morphology, fitness (e.g., increased resistance to cold/frost, drought, or salinity) or modified reproductive characteristics. Some traits such as resistance to certain herbicides are already known from existing GM crops and their previous assessments identified issues of concern and/or risks, such as the development of herbicide resistant weeds. Other traits in nGM plants are novel; meaning they are not present in agricultural plants currently cultivated with a history of safe use, and their underlying physiological mechanisms are not yet sufficiently elucidated. Characteristics of some genome editing applications, e.g., the small extent of genomic sequence change and their higher targeting efficiency, i.e., precision, cannot be considered an indication of safety per se, especially in relation to novel traits created by such modifications. All nGMs considered here can result in unintended changes of different types and frequencies. However, the rapid development of nGM plants can compromise the detection and elimination of unintended effects. Thus, a case-specific premarket risk assessment should be conducted for nGM plants, including an appropriate molecular characterization to identify unintended changes and/or confirm the absence of unwanted transgenic sequences.

Broadening the GMO risk assessment in the EU for genome editing technologies in agriculture

“…FokI) at a predefined site in the genome of a target organism. These techniques have been largely outcompeted by the CRISPR/Cas system in recent years [13]. Nevertheless, some products developed by these earlier techniques are permitted to be cultivated and sold, at least in the U.S. [31], e.g.…”

“…Whilst ODM may involve changes to only small number of DNA bases, there is the possibility of off-and ontarget effects. Although there are, as yet, no published data examining the frequency of unintended effects with ODM [4,13,93], this does not mean that they do not occur. The possibility of oligonucleotide integration cannot be excluded [4].…”

“…Genome editing has also been termed "genome engineering", implying greater intervention to the genome than simply "editing" [7], and are referred to "new genomic techniques" by the European Commission [8]. In this paper, we use the terminology of genome editing to encompass techniques such as oligonucleotide-directed mutagenesis (ODM), zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), meganucleases and clustered regularly interspaced short palindromic repeats/CRISPR-associated (CRISPR/Cas) techniques [9][10][11][12] with CRISPR/Cas becoming the most widely used genome editing technology [13].…”

New Plant Breeding Techniques in Citrus for the Improvement of Important Agronomic Traits. A Review

“…This led to the conclusion that neither system can be regarded as superior. In addition, NPBTs are differentially regulated throughout the world (Eckerstorfer et al, 2019;Friedrichs et al, 2019). In the USA, NPBT crops are exempt from the strict rules and regulations of the USDA (Waltz, 2016), considering genome editing as a method of conventional breeding, only faster.…”

Current status on the modification of the scope for GMO regulation on the gene edited plants with no remnants of inserted foreign DNA fragments

“…으로 발전하고 있는 식물신육종기술들에 대하여 두려움으 로 불안함과 함께 정확한 정보의 공유를 요구하고 있다 (Araki and Ishii 2015;Panella et al 2015;Jung et al 2018;Eckerstorfer et al 2019a). 특히 유전자교정기술은 최근 몇 년 사이에 급속도로 발전 되어 제2세대 기술(TALEN), 제3세대 기술(CRISPR-Cas9)까 지 새로운 기술들이 실용화에 근접하였으며, 향후 보다 효 율적이고 정확하며, 안전성이 우수한 새로운 기술들이 개발 될 것으로 전망된다 (Hilsher et al 2017;Lee 2018 (EASAC, 2015;Jouanin et al 2018).…”