Breeding a nonallergenic peanut

By Peter Beetham,CEO of CIBUS, an agricultural biotech that specializes in non-transgenic gene editing.

Peanut butter has been a beloved staple of school lunches for what seems like forever. But peanut allergy is a serious condition that can cause fatal reactions when not immediately treated. Peanut allergy afflicts 2–3 percent of children and teenagers in the United States, which amounts to approximately 1.6 million people across the country. Various therapies are under investigation for peanut allergy—including Aimmune’s immunotherapy that’s being reviewed by the Food and Drug Administration (FDA) — yet these don’t target the root problem: the peanut itself.

But what if farmers could grow a peanut that doesn’t cause an allergic reaction in the first place?

While researchers have understood the genetics behind the allergy for quite some time, there’s been a holdup on developing a peanut that doesn’t contain these genes. Plant breeders have lacked the tools needed to make the precise genetic changes required to neutralize the triggers for an allergic response.

Until now.

It’s important to understand how peanut allergies came to exist in the first place. Over millennia, genetic changes in peanuts have happened either randomly or been selected by farmers for different breeding techniques. This long and laborious process has meant that certain unfavorable characteristics—such as proteins that trigger life-threatening allergies—have persisted in peanuts and other commercial crops.

But recent advances in gene-editing tools can make changes at the precise place in an organism’s DNA that cause these allergic reactions. During an allergic response, the peanuts’ storage proteins can trigger a massive overproduction of histamines (chemicals that kick the immune system into overdrive), throwing the body into shock. It’s a harmful analogue to what happens when we’re frightened and the body produces a flood of adrenaline to turbocharge our system.

Using “molecular scissors” (CRISPRs or TALENs) to knock out the entire genes that produce protein storage won’t work, however, because then you wouldn’t have a peanut at all. Instead, we need to edit the surface of the protein, so no allergic response is triggered, and we need to do that without changing the function of the genes controlling the storage proteins.

This is a delicate task. If we can envision the relationship between the trigger and the allergic response as a lock and key (respectively), we’re trying to change the lock so that the key won’t fit. In other words, we’re eliminating an undesirable function of a protein while preserving its original structure.

For this, we need a far more precise set of tools than those available in the early years of gene editing. Molecular scissors allow one to eliminate a part or all of a gene, but they don’t allow researchers to alter the gene itself. That requires an additional gene editing tool.

Think of a gene as a word constructed out of letters. In genetics, these letters are called nucleotides. A tool known as GRON (Gene Repair OligoNucleotide) functions as a spellchecker that the cell recognizes as a guide to correct its DNA. When guided to the precise letter(s) of DNA involved in triggering the allergic reaction, this guide will harness the plant’s own repair mechanisms to change the spelling of the gene so that the key no longer fits the lock, so to speak. The GRON is the technological advance that, in combination with molecular scissors, enables researchers to precisely edit a gene to changes its function without altering it structure.

In some cases, this can be a complex task because the allergic reaction involves more than one gene, and changing the trigger that causes the allergic response requires multiple spelling changes. This can be accomplished only with technology that can edit rather than simply knock out genes. This is why we refer to the combination of the GRON with molecular scissors as “precision gene editing.”

However daunting the task of making these spelling changes might be, once accomplished, they will yield benefits far beyond their immediate application to peanut allergy. Nature tends towards efficiency, and a number of the genes and genetic pathways involved in peanut allergy are also involved in other allergies. It also means that in dealing with peanut allergy, we also get a head start in dealing with other plant-related allergic responses ranging from gluten intolerance to reactions to grass.

We have the tools to tackle various allergies, and we know the tools work. The combination of GRON and molecular scissors has already produced a canola that resists plant diseases, as well as crops (including canola, flax and rice) that can tolerate herbicides. By applying this to an allergy-safe peanut, we can foresee a day when parents won’t live in fear of allergic exposure when sending their child off to a friend’s house for a playdate.