Gene Editing of Wheat to Reduce Coeliac Disease Epitopes in Gluten

Abstract

By using gene editing technologies such as CRISPR/Cas, precise modifications can be made in the genome. CRISPR/Cas is especially valuable for targeted mutagenesis in polyploids, as it can induce mutations of multiple alleles simultaneously, to obtain regenerants that are homozygous for the desired mutation. A range of gene-edited traits have been developed in hexaploid bread wheat, including various nutrition and health-related traits, plant architecture, pest and disease resistance, tolerance to abiotic stress, and traits that enable more efficient breeding. Wheat is also known as a cause of some human diseases, particularly coeliac disease (CD), with a prevalence of 1–2% of the population. In the EU alone, at least 4.5 million people suffer from it. CD is a chronic inflammation of the small intestine, induced and maintained in genetically predisposed individuals by the consumption of gluten proteins from wheat, barley and rye. As there is no cure, patients must follow a life-long gluten-free diet. The dominant epitopes in gluten proteins that trigger the disease, have been characterized, but they cannot be removed by classical breeding without affecting baking quality, as it concerns over 100 gluten genes that occur partly as blocks of genes in the genome of wheat. Using gene editing, two studies have shown that it is possible to modify the epitopes in several alpha- and gamma-gliadins simultaneously, while deleting some of the genes completely. In some lines more than 80% of the alpha-gliadin genes were modified. These proof-of-principle studies show that it is feasible to use gene editing, along with other breeding approaches, to completely remove the CD epitopes from bread wheat. Gene-edited coeliac-safe wheat will have economic, social and environmental impact on food security, nutrition and public health, but the realisation will (partially) depend on new European legislation for plants produced by gene editing.