Scientific opinion addressing the safety assessment of plants developed using Zinc Finger Nuclease 3 and other Site‐Directed Nucleases with similar function

Abstract

The European Commission requested that the EFSA Panel on Genetically Modified Organisms deliver a scientific opinion related to risk assessment of plants developed using the zinc finger nuclease 3 technique (ZFN-3) which allows the integration of gene(s) in a predefined insertion site in the genome of the recipient species. Since other nucleases with a similar function to ZFN are considered in this opinion the term site-directed nuclease 3 (SDN-3) is used to describe the technique rather than ZFN-3 specifically. The EFSA GMO Panel considers that its guidance documents are applicable for the evaluation of food and feed products derived from plants developed using the SDN-3 technique and for performing an environmental risk assessment. However, on a case-by-case basis lesser amounts of event specific data may be needed for the risk assessment of plants developed using the SDN-3 technique. The EFSA GMO Panel compared the hazards associated with plants produced by the SDN-3 technique with those obtained by conventional plant breeding techniques and by currently used transgenesis. With respect to the genes introduced, the SDN-3 technique does not differ from transgenesis or from the other genetic modification techniques currently used, and can be used to introduce transgenes, intragenes or cisgenes. The main difference between the SDN-3 technique and transgenesis is that the insertion of DNA is targeted to a predefined region of the genome. Therefore, the SDN-3 technique can minimise hazards associated with the disruption of genes and/or regulatory elements in the recipient genome. Whilst the SDN-3 technique can induce off-target changes in the genome of the recipient plant these would be fewer than those occurring with most mutagenesis techniques. Furthermore, where such changes occur they would be of the same types as those produced by conventional breeding techniques. ABSTRACTThe European Commission requested that the EFSA Panel on Genetically Modified Organisms deliver a scientific opinion related to risk assessment of plants developed using the zinc finger nuclease 3 technique (ZFN-3) which allows the integration of gene(s) in a predefined insertion site in the genome of the recipient species. Since other nucleases with a similar function to ZFN are considered in this opinion the term sitedirected nuclease 3 (SDN-3) is used to describe the technique rather than ZFN-3 specifically. The EFSA GMO Panel considers that its guidance documents are applicable for the evaluation of food and feed products derived from plants developed using the SDN-3 technique and for performing an environmental risk assessment. However, on a case-by-case basis lesser amounts of event specific data may be needed for the risk assessment of plants developed using the SDN-3 technique. The EFSA GMO Panel compared the hazards associated with plants produced by the SDN-3 technique with those obtained by conventional plant breeding techniques and by currently used transgenesis. With respect to the genes introduced, the SDN-3 technique...

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

“…EFSA's opinion on SDN-3 from 2012 [26] considers that genome editing can "minimize hazards" or that offtarget changes would be "fewer than those occurring with most mutagenesis techniques" and be "of the same types as those produced by conventional breeding techniques". However, as described above, a large number of publications since 2012 demonstrate that several types of genomic irregularities can often be generated using SDN-1, SDN-2 and SDN-3 applications.…”

“…Therefore, risk assessment guidelines will have to be examined, and potentially revised to ensure they capture unintended effects caused by the genome editing process. EFSA has issued an opinion on the risk assessment for the genome editing of plants where genes are inserted using site directed nuclease-3 (SDN-3) techniques [26] and has received a mandate from the Commission to produce an opinion on whether these risks are applicable to genome-edited plants not carrying novel genes, i.e. using site-directed nuclease-1 (SDN-1) and site-directed nuclease-2 techniques (SDN-2).…”

Revisiting Risk Governance of GM Plants: The Need to Consider New and Emerging Gene-Editing Techniques

“…The EFSA GMO Panel opinion addressing the safety assessment of plants developed using Zinc Finger Nuclease and other Site-Directed Nucleases with similar function (EFSA Panel on Genetically modified organisms (GMO), 2012) and the Institute for Prospective Technological Studies and Institute for Health and Consumer Protection (both from the Joint Research Centre at the European Commission) (Lusser et al, 2011) have set forth three major categories of new and emerging gene-editing techniques (Box 1).…”

“…Products of new and emerging techniques, according to the ECJ ruling, are all classified as GMOs, thus, raising a question of how the framework will be implemented. In particularly, an open question remains how to adapt guidance to support assessment of products arising from new and emerging gene-editing techniques (Lusser et al, 2011; EFSA Panel on Genetically modified organisms (GMO), 2012; Jones, 2015a; The Norwegian Biotechnology Advisory Board, 2018).…”

Biotechnological and Digital Revolution for Climate-Smart Plant Breeding

“…The use of transgene-free methods can lead to genome-edited plants (SDN1 and SDN2 on case-by-case), which are indistinguishable by spontaneously mutated crops or mutants obtained by classical mutagenesis approaches (i.e., ethyl methanesulfonate, ionizing radiation) [115]. Therefore, in the European Union, a distinction in the legislation supporting the approval route toward commercialization of the edited plants deriving by SDN1, SDN2, and SDN3 methods was proposed [127,128]. However, the latest ruling by the European Court of Justice [129] requires that crops generated by using gene-editing techniques such as CRISPR must go through the same lengthy approval process as conventional genetically modified (GM) plants [130].…”