The Potential of NGTs to Overcome Constraints in Plant Breeding and the Regulatory Implications

Conventional plant breeding relies on the occurrence of chromosomal crossover as well as spontaneous or non-targeted mutations in the genome induced by physical or chemical stressors. However, constraints exist concerning the number and variation of genotypes that can be achieved in this way as the occurrence and combination of mutations are not equally distributed across the genome. The underlying mechanisms and causes of reproductive constraints can be considered the result of evolution to maintain the genomic stability of a species, while at the same time allowing necessary adaptions. A continuous horizon scan was carried out to identify plants derived from new genomic techniques (NGTs) which show that CRISPR/Cas is able to circumvent at least some of these mechanisms and constraints. The reason for this is the specific mode of action: While physico-chemical mutagens such as radiation or chemicals merely cause a break of DNA, recombinant enzymatic mutagens (REMs) such as CRISPR/Cas additionally interfere with the cellular repair mechanisms. More recently developed REMs even expand the capabilities of NGTs to introduce new genetic variations within the target sequences. Thus, NGTs allow to introduce genetic changes and combinations that are unknown in the current breeding pool, and that are also unlikely to occur from any previously used breeding methods. The resulting genotypes may need to be considered as ‘new to the environment’. The reasons for the above can be identified in the mode of action of the REMs. CRISPR/Cas catalysed reactions in particular can interfere with and overcome 1) cytogenic features such as repair mechanisms; 2) factors influencing recombination and stability of the genome such as crossovers; 3) gene copies with and without proximity and 4) certain regulatory elements. The technical potential of NGTs should also be taken into account in regulatory provisions. Previously unknown genotypes and phenotypes may negatively impact plant health, ecosystems, biodiversity and plant breeding. It must further be acknowledged that the different outcomes of NGTs and conventional breeding are not always evident at first sight. As a starting point, within a process-oriented approval process, molecular characterisation can inform the following steps in risk assessment and guide requests for further data.