ByDerek Norman,
Contributor.
Forbes contributors publish independent expert analyses and insights.
Derek Norman is VP of Agriculture Venture Investments, Leaps by Bayer.
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Summary
Food allergies impact over 22 million Americans, with current options often limited to avoidance or risky immunotherapy. New research reveals the immune system actively learns food tolerance, rather than allergies being a default. Concurrently, biotech companies are innovating with AI and gene editing to potentially transform allergy treatment and enable genetically engineered hypoallergenic crops.
Researchers are testing new ways to expose patients to allergens in a way that builds their immune tolerance without triggering a severe allergic reaction. getty
More than 22 million people in the U.S. have food allergies, and that number is growing every year. The resulting economic burden amounts to $370.8 billion annually. Despite the high cost to the healthcare system, there is no broadly effective cure for food allergies, and the only option for many is to simply avoid the dangerous foods, a burden often d with the families of those with food allergies.
As any person with a food allergy will tell you, they do everything they can to avoid exposure. But despite their best efforts, approximately two hundred thousand people end up in the emergency room each year with severe allergic reactions.
The good news is that people can sometimes outgrow their food allergies. Exposure immunotherapy is a promising therapeutic approach designed to help patients develop tolerance to the allergen. However, it is expensive and time-consuming, requiring regular doctor’s office visits over the course of months, and patients can sometimes experience anaphylactic shock—a traumatic experience that causes some to stop treatment.
Outsmarting the Immune System
The fact that people can develop tolerance to foods they were previously allergic to suggests that allergies are not necessarily an inherent property of a person’s immune system. While it was previously thought that not developing a food allergy was simply a default response, scientists are now discovering that our immune system has to proactively learn to recognize food as safe.
Beth Sattely, an Associate Professor of Chemical Engineering at Stanford University who studies how plant molecules affect human health, has been investigating the mechanisms by which we develop tolerance to common food allergens.
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“We do know that once an individual becomes tolerant to a food, it’s much less ly that they’re ever going to develop food allergy,” says Sattely. Her research focus is understanding which specific components in plants promote tolerance and leveraging that knowledge to prevent allergies from developing in the first place.
A recent study from the Sattely lab, published in Science Immunology, investigated oral tolerance to corn, wheat, and soybeans in mice. The results suggest that rather than responding to entire proteins, the immune system recognizes certain protein fragments as signals of safe dietary exposure.
“There’s a whole language of [plant protein] signals that we’re just starting to decode and understand, especially in the context of your immune system,” says Sattely.
Identifying those proteins may hold a key to developing safe exposure methods and ultimately lead to new therapeutics.
“I think that if we really understand how tolerance works, there could be a way where we can essentially have a food tolerance vaccine. By exposing people to food under the right conditions and at the right time, we could get them programmed down the right path for tolerance rather than allergy,” says Sattely.
A natural question to ask is: Why do some plants trigger an allergic response in the first place? Many of the top plant-based allergens are found in seeds, and the reaction some people have to them may be inextricably linked to their function.
“One possibility is that it’s just a byproduct of their natural function,” says Sattely. “These proteins are very stable and they protect seeds [from degradation], and that renders them perhaps more immunogenic than another protein that might be degraded more easily.”
Mapping Plant Allergens
Researchers have made attempts to create hypoallergenic peanut and wheat varieties. For example, an agricultural startup IngateyGen is using CRISPR to delete the genes responsible for causing peanut allergy as part of an NSF-sponsored Small Business Innovation Research (SBIR) grant. Another research team, headed by Professor Eduard Akhunov at Kansas State University, is working on gene-edited wheat with fewer immunogenic gluten proteins.
However, deleting entire proteins from the plant’s genome may have unintended consequences. After all, these proteins, often in seeds, may play an important functional role. For example, gluten is essential for baking—it is what makes bread rise and gives bagels their delectably dense texture. Without gluten, many of our favorite foods might not be the same.
To overcome this issue, a biotech company called Ukko has developed an AI-driven computational approach to figure out how to make problematic food proteins less allergenic without compromising their function. (Disclosure: I have served on the Board of Directors at Ukko since Leaps by Bayer first invested in the company in 2020.) They combine this computational approach with gene editing to redesign proteins, with the ultimate goal of creating safer allergy immunotherapies.
“We can study what exactly it is on these proteins that the immune system recognizes, and very precisely blur those elements, so that the immune system no longer recognizes them,” explains Yanay Ofran, Chairman and Co-founder of Ukko.
To accomplish this, Ukko has built one of the largest clinically validated molecular maps of food allergies, comprising hundreds of blood and tissue samples. By comparing the samples from patients who have an allergic reaction to those who do not, Ukko can learn what parts of the protein are responsible for causing allergies and selectively alter those parts.
The result is a protein that is almost identical to the original one but lacking the elements that cause sensitivity. That edited version is tested on patient immune cells in the lab to ensure that they elicit the appropriate therapeutic response without causing harm.
“Our core innovation is studying the individual protein that causes the problem and making a safe and efficacious version of that protein,” says Ofran. “We’re testing it in patients [with peanut allergies], where we try to keep all the elements that can reeducate the immune system to tolerate peanuts, but we’ve removed the elements that can trigger allergy.”
Ukko’s peanut allergy treatment, UKK-0018, recently entered clinical studies. The first safety, tolerability, and preliminary efficacy data are expected in 2027.
Hypoallergenic Foods – Why Not?
The quest to understand the nature of food allergies reaches far beyond designing new therapeutics. It opens the possibility that future breeding and plant engineering efforts could optimize crops not only for yield and food quality, but also for immune tolerance.
Perhaps we could use biotechnology to create crop varieties that do not cause allergies in the first place, for example by genetically engineering hypoallergenic peanut seeds and making all the peanuts in the world safe.
“Technically, we’re very close to the point, or maybe even past the point where this is scientifically and technically possible,” says Ofran. “Now the question becomes: Is it viable financially and business-wise to do this?”
Thank you to Katia Tarasava for additional research and reporting on this article.
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