Dutch scientists have cracked the gene code to make ‘gluten-safe’ wheat

Researchers from Wageningen University in The Netherlands are using CRISPR-Cas9 to target and destroy the toxic antigens in gluten, called epitopes, without damaging the unique baking characteristics that gluten gives baked goods.

However, it is a highly complicated process.

For starters, modern bread wheat has 16 billion DNA letters, five times the size of the human genetic code.

The gluten genes are located within this complex wheat genome as a repeat of multiple genes – sometimes up to 50 genes in one chromosome.

“Not all of these genes have the toxic epitopes and [with this new CRISPR-Ca9 technique] it’s possible to remove part of them and leave the non-toxic ones,” said Jan Schaart, a researcher at Wageningen Plant Research.

Benefits for gluten intolerant population

The approach is entirely new and will have an enormous impact for the gluten intolerant community, which is estimated to be 1%-2% of the global population and growing.

Another one in five Americans, according to a Gallup Poll, say they actively try to include gluten-free foods in their diet.

However, following an entirely gluten-free diet is not easy, as wheat gluten is often added to processed foods for its viscoelastic properties.

Recent research has suggested that celiac disease could be caused by the bacterial enzyme, microbial transglutaminase – heavily used as a food binder in industrial processing of baked goods, meat, dairy and other food products – which is unlabeled.

The idea of using gene editing in this field was derived from the Ph.D. thesis of Wageningen University doctoral candidate Aurélie Jouanin.

“It sounds very simple, but so far, the group has managed to mutate wheat strains to lack particular gluten epitopes,” said Schaart.

“The researchers have also established new methods for checking which genes have been modified, and which need removing.”

GM regulations

Though the CRISPR-Cas9 system was discovered back in the 90s, it has only recently taken the scientific world by storm.

CRISPR-Cas9 – which denoted Clustered Regularly Interspaced Palindromic Repeats/CRISPR-associated genes & proteins – is a revolutionary, albeit controversial, technology that enables genetic material of viruses, bacteria, cells, plants and animals to be changed relatively simply, very accurately and efficiently.

This is achieved by making genetic changes that result in altered properties, or by adding entirely new genetic information.

However, the regulation of genetic modification (GM) in Europe is currently a hot topic, precisely because of its role in editing the genes of plants, animals and even humans.

In 2018, the higher court of the EU decided mutagenesis techniques such as CRISPR/Cas9 should fall under GMO law, which requires ‘gluten-safe’ wheat lines to undergo extensive food safety and environmental tests.

Researchers have hit back arguing that new plant breeding techniques (NPBTs) developed over the past two decades have provided ample possibilities for efficient plant research and trait development.

In an article published in Trends in Biotechnology, the authors list a raft of examples conducted by research facilities around the EU that may be affected by the proposal if it were adopted into EU legislation.

Gamma irradiation

For her thesis, Jouanin also investigated the effect of gamma irradiation, which does not fall under EU restrictions.

However, this technique potentially removes a number of other genes from the wheat genome, not just the toxic ones.

“It is less precise,” said Schaart.

“That's the advantage of this novel, new technique [using CRISPR-Cas9] – you can direct it to the genes you want to target.

“We say it is safer than transitional techniques for this reason. But, the EU says it's a new technology with no history of use, so it needs strict regulation.”

Regulations elsewhere are not as strict, possibly providing a loophole.

For example, noted Schaart, GM wheat lines could be commercialized in the US and then imported into EU, labeled not as ‘being made with a new technique’, but just as a safe food.

“This is an interesting theme and something that will happen in the near future. Products made via new technologies will come to Europe. This is a potential opening.”

However, this is currently a moot point. The wheat gluten project has been ongoing for five years, yet the discovery is still five to 10 years away from commercialization.

The team at Wageningen University are now seeking further funding, as well as collaboration partners.