CRISPR biofortified foods

Nutritional improvement of crops is one of the fields set to gain from the advent of genome editing. Let’s take vitamin D3. People suffering from its deficiency in the world number about one billion. Plants do not contain it naturally, but some of them (solanaceae) are able to produce its precursor (cholesterol) within a biosynthetic pathway that leads to the synthesis of certain secondary metabolites (glycoalkaloids). Luckily, they can be induced to accumulate provitamin D3 by switching off the gene responsible for this reaction.

A targeted genetic intervention similar to a spontaneous mutation can do the trick, as shown in a paper published in 2022 in Nature Plants by researchers at the CNR Institute of Sciences of Food Production in Lecce, Italy, and the John Innes Center in Norwich, UK.
The study has attracted international media attention because provitamin D3-enriched tomatoes represent the vanguard of future products: foods modified to meet real health needs, with an eye to the trend of personalized nutrition.

“The result of editing and subsequent crosses is that the biofortified tomato differs only in a few bases from the parental plants. According to initial calculations, a couple of tomatoes a day should be enough to meet a person’s needs,” said Angelo Santino, from the CNR, when I interviewed him for the website AgriScienza. In short, these tomatoes have good hopes of not being penalized from the regulatory point of view in many countries and of receiving a warm welcome from consumers.

The human body needs this vitamin for calcium regulation, and thus for bone growth and health. Rickets and osteoporosis, moreover, are not the only risk to consider: cancer, Parkinson’s, dementia, and other diseases are also associated with vitamin D3 deficiency. To get enough of it, it is necessary to consume foods of animal origin – such as fish, eggs and liver – and then rely on the sun to convert the precursor into the active form.

Some mushrooms can produce provitamin D2, but it is less stable and effective. Ultimately, many people would be in need of targeted supplements (risk factos include veganism, high latitudes, dar skin, age). In Europe, however, supplements are less popular than in the US; in fact, as many as 40 percent of Europeans are deficient versus 20 percent of Americans.

The trick used by Santino and colleagues was to knock-out the gene coding for the target enzyme (Sl7-DR2). Because the metabolic pathway for glycoalkaloid synthesis is not essential for tomato growth, the mutant lines were unaffected by the change, according to early results from the first field trial in UK. Provitamin D3 accumulated in the fruits and even more in the leaves, and laboratory tests showed that about 30% is converted into the active form by UV light .

“By growing these plants in southern Italy, where solar radiation is much stronger than in Britain, and perhaps drying the fruits in the sun, the level could increase even more,” Santino argues. The leaves also could be used to make supplements, which today are based on a substance excreted by sheep and purified from wool (lanolin).

Animal studies are needed to prove the health effects of fortified foods, but CNR and the John Innes Center have gained experience in this area as well. A few years ago, they developed tomato lines enriched in polyphenols using a classical genetic engineering approach (trangenesis). Experiments with mice fed tomatoes identical in all but the desired substances proved that a line enriched with different classes of polyphenols (flavonols, stilbenes, anthocyanins) may reduce bowel inflammation and is good for the gut microbiota.

Why are tomatoes the food of choice? “This plant offers many advantages: it is one of the most cultivated in the world, it grows well in greenhouse conditions, and its fruits can be eaten raw, without damaging the thermolabile substances,” says the CNR researcher. Typically, researchers use a cultivar called moneymaker, but the same approaches can be applied to local varieties and even other species such as peppers, provided that efficient transformation and regeneration protocols are devised.

Widening the focus to nutritional security as a whole, we must consider that consumers have different dietary deficiencies, in terms of vitamins, secondary metabolites, and other micronutrients, which vary according to age, gender, disease, and lifestyle. “In a future that is not yet at hand, we will be hopefully able to match each person to the most suitable foods. For example, those having Crohn’s disease or colitis, cardiovascular or neurovegetative disorders.”

Getting closer to this goal will probably require a range of metabolic engineering approaches, and also the development of rapid tests able to verify product-by-product the real potential for preventing human diseases.

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