Synthetic Biology and AI to Remove Food Allergy

Allergies are increasingly common pathologies in human society. In the past, it was believed that they were due to an exaggerated reaction of the immune system to a specific antigen or a hypersensitive reaction. Today we know that it is actually the harmlessness of the external agent that leads to pathogenesis, paradoxically. In fact, there is no failure of the immune system, apart from attacking a harmless substance. This ends up damaging the adventitious tissues by a multitude of molecular mechanisms including cytotoxicity. There are many types of allergies and ways of developing them, but in general, we can establish some general guidelines. Repeated overexposure to certain protein regions and the lack of a particular enzyme that hydrolyzes that region usually results in allergy over time. Sometimes it is avoidable, sometimes not, because it has a high genetic component. For example, in areas where olive trees are cultivated, many olive pollen allergy sufferers arise.

The fact that these ailments are becoming more and more frequent is mainly due to the contamination of water, the atmosphere, and the food industry. While many additives are harmless or even beneficial to health (such as ascorbic acid, a great preservative) there are other molecules that can interact with our health in a negative way, and sometimes end up developing an allergy.

Current Strategies

Of course, there are several current treatments to treat allergies. Antihistamines have saved many lives. However, treating food allergies is more difficult. Synthetic biology can help solve the root of the problem. This is the thinking of Ukko, a start-up founded in Israel that adopts two main strategies: designing foods that are normally allergic (such as wheat products that contain gluten) so that they are no longer allergic and designing edible drugs that prevent the immune reaction to the antigen that causes the allergy.

The fact is that to accomplish this feat, one can make use of the new technologies available to them. In this case, the difficulty lies in being able to identify the amino acid sequence of the allergens and their three-dimensional structure. A field of artificial intelligence, deep learning, can test millions of structural combinations that make it possible to study the effectiveness of the immune response to the protein. This protein can then be modified in the food-producing organism to make it hypoallergenic, once we have this information.

Other strategies are as striking as the construction of a biological microsensor based on mammalian cells. Or put another way, a human cell designed to quantify a circuit of synthetic signaling reactions for histamine release triggered by allergens. This is also a breakthrough in personalized medicine.

What is clear is that the pull of artificial intelligence will lead to large outlays by investors in increasingly innovative healthcare strategies. The ability to screen drugs and their respective targets open the door to another model of in silico research. Vaxine is a veteran example of an Australian startup using artificial intelligence to discriminate compounds as adjuvants in vaccines, focusing on treatment for communicable diseases, allergies, and cancer.

It should be noted that there are four types of allergy, being the one we are dealing with in the group of anaphylactic allergies. Within food allergies there is a group that affects 1 to 10% of the population in developing countries, although it depends greatly on geographical location and age; it has its origin in an abnormal interaction between immunoglobulin E (IgE) and the epitope of the allergen, i.e. the amino acid surface that is recognized by the hypervariable region of the antibody. This type of allergy is as serious as it is avoidable, since, as mentioned above, it would be sufficient to delete this protein region of the product by means of genetic engineering. A peanut allergy sufferer could eat peanuts again without any problem, as is the case with gluten-free foods. However, the case of gluten is different, since it is not so sophisticated and detracts from the nutritional quality of the food - it is a series of denaturing chemical reactions - and so we are already studying how to eliminate this gluten using synthetic biology. It should be noted that many of these proteins can be substituted for nutritional value, but not for the function they perform. For example, the baking of gluten-free flours is much more costly in terms of energy, since it does not generate these three-dimensional networks together with the arabidoxylans and its kneading is of poorer quality. All these things must be taken into account when designing a hypoallergenic protein substitute, so that it is also able to perform its function relatively normally or even improve the natural functionality (nutritional capacity, higher performance...).

The Future

New strategies targeting transient genetic modification of T lymphocytes are under study. With a clear understanding that the problem lies in that misguided immune system response, and not in an overreaction as previously thought, we now hold the key to taming food allergy outbreaks once and for all, even predicting future allergies by overexposure to an antigen, whether in food or in another source of contact. Systems biology will play a key role in the coming years, connecting biological circuits with feedback from each iteration studied and driven by AI.

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