How Can Gene Editing Solve Food Allergies

Commonly encountered allergic conditions include Asthma, Allergic Rhinitis, Atopic Dermatitis, Urticaria, Conjunctivitis, and different food allergies. These are caused by a trigger of immune response in the body, which results in eosinophilic inflammation and skewing of the immune responses towards the type 2 helper cells. Moreover, allergic conditions like food allergies also involve the release of certain cytokines like Interleukin 4, Interleukin 5, and Interleukin 13, which cause the production of IgE in the body. This is accompanied by differentiation of mast cells, growth of eosinophils, and migration and activation of multiple pathological abnormalities. Despite the high numbers of allergic reactions experienced by thousands across the world towards multiple food sources, there is no definite treatment for them. Multiple management remedies may be used, which include medicines like antihistamines, corticosteroids, bronchodilators, and other immune therapy measures; however, these are costly and need to be consumed life long. Gene Editing has emerged as a convenient and effective treatment for food allergies by editing the allergen, which is triggering the reaction and allow the individuals to consume these foods without life-threatening allergic reactions. (1)

What is the CRISPR/CAS system?

Even since the development of the CRISPR/CAS system, new doors have been opened for the development of gene modification and using these not only allows researchers to carry out their studies more efficiently but also makes people’s lives easier every day. This system was originally found in the Bacteria and Archae; however, it was quickly developed to allow gene editing and modification of unique DNA sequences via the help of a protein known as Cas9. A combination of the CRISPR-Cas system allows for the breaking of the double strand of the target DNA and addition or deletion of a particular gene, which will provide favorable results. This system has been previously used to edit and manipulate the genome of multiple types of organisms and species, which include plants, Zebrafish, Drosophila, along with animals like vertebrates and even humans. The ability of this system to be able to make pinpoint changes in the genome has given it a lot of importance, especially when it comes to research purposes intended to improve the quality of life of humans and find cures and preventative measures for diseases.

The constant development and studies conducted on this system have allowed for some important modifications to be made for this system which includes single site-directed gene editing, which may allow point mutations, translocations, insertion, and deletions to be made at the target site. This system may also be used for the purpose of high throughput genetic screening. Modifications have also been made in some of the CAS proteins like the Cas9, which is edited to lower its off-target cleavage and may nick one strand at a time. (2)

CRISPR/CAS system for Food Allergies

CRISPR/Cas system has recently been used increasingly to study allergic diseases, the type of genes that cause them, and how these may be altered to facilitate humans. Amongst the various studies, a majority have been conducted to investigate the role of specific genes in causing allergic reactions, particularly those that lead to food allergies. An important example of one such gene is the MUC18, which was investigated by Chu et al. The CRISPR system was used to remove this gene from the primary nasal airway in the human, which resulted in a reduction of the Interleukin 8 response, in turn proving the role of this gene in promotion of inflammation. (3)

This system is also gaining popularity for its role in forming mutant mouse models, which may be used to study allergic and immunologic diseases and, in turn, find more definite and precise treatments for such conditions. Moreover, CRISPR/Cas is rapidly becoming the primary tool to create mutant mouse models of diseases, including allergic and immunologic diseases, due to the ease, precision, and flexibility of this technique. (4)

Examples of Common Food Allergies and Role of CRISPR System

Peanut Allergy

Peanut allergy is amongst the most common food-caused allergies and can prove to be deadly if not managed immediately. This allergic reaction is mediated by the IgE antibodies, which leads to an intense hypersensitivity reaction. However, despite the severity of this allergic reaction, there was no definite cure for the condition until the CRISPR system came along. Reports have shown that the Ps-transcriptional gene silencing methods can be used successfully to eliminate the allergen production in the peanuts by targeted degradation of the RNA endogenous to them. (5)

Cow Milk

Cow Milk is another food source that has been popularly linked to causing food allergies due to the intolerance in some individuals to certain contents. Even though it is a very popular food ingredient that is consumed by a majority around the world, it may not be suitable for everyone. Cow Milk Allergy is a condition in which people may be diagnosed from a very young age and is found to prevail in 0.3 to 0.5% of the worldwide population. This condition involves the inability of the individuals to absorb and utilize the cow milk ingredient and causes significant negative digestive symptoms like diarrhea and flatulence. Using Gene editing technologies like CRISPR can efficiently remove the gene that may be causing the allergy in the individual, which in turn significantly reduces its allergic potential and increases its possible consumption in young children. (6)

Gluten-Free Wheat

Coeliac Disease is autoimmune in nature and is associated with food sources such as wheat. And is found to prevail in at least 1 to 2% of the population worldwide. This may be mainly caused by certain immunogenic epitopes like α-, γ-, and ω-gliadins, which lead to a chronic inflammatory reaction in certain parts of the digestive tract like the small intestine. However, gene-editing technologies like the CRISPR-Cas9 system may allow the removal of these immunogenic epitopes and gluten genes from the wheat, which in turn leads to better tolerability of this food source in the affected population. (7)

References:

1. Chuang YH, Yang YH, Wu SJ, Chiang BL. Gene therapy for allergic diseases. Curr Gene Ther. 2009 Jun;9(3):185-91. doi: 10.2174/156652309788488604. PMID: 19519363.
2. Naeem M, Majeed S, Hoque MZ, Ahmad I. Latest Developed Strategies to Minimize the Off-Target Effects in CRISPR-Cas-Mediated Genome Editing. Cells. 2020;9(7):1608. Published 2020 Jul 2. doi:10.3390/cells9071608
3. Chu HW, Rios C, Huang C, Wesolowska-Andersen A, Burchard EG, O’Connor BP, Fingerlin TE, Nichols D, Reynolds SD, Seibold MA. CRISPR-Cas9-mediated gene knockout in primary human airway epithelial cells reveals a proinflammatory role for MUC18. Gene Ther. 2015 Oct;22(10):822-9. doi: 10.1038/gt.2015.53. Epub 2015 Jul 2. PMID: 26043872; PMCID: PMC4600011.
4. Goodman MA, Moradi Manesh D, Malik P, Rothenberg ME. CRISPR/Cas9 in allergic and immunologic diseases. Expert Rev Clin Immunol. 2017;13(1):5-9. doi:10.1080/1744666X.2017.1241711
5. Dodo HW, Konan KN, Chen FC, Egnin M, Viquez OM. Alleviating peanut allergy using genetic engineering: the silencing of the immunodominant allergen Ara h 2 leads to its significant reduction and a decrease in peanut allergenicity. Plant Biotechnol J. 2008 Feb;6(2):135-45. doi: 10.1111/j.1467-7652.2007.00292.x. Epub 2007 Sep 3. PMID: 17784907.
6. Sun Z, Wang M, Han S, et al. Production of hypoallergenic milk from DNA-free beta-lactoglobulin (BLG) gene knockout cow using zinc-finger nucleases mRNA. Sci Rep. 2018;8(1):15430. Published 2018 Oct 18. doi:10.1038/s41598-018-32024-x
7. Jouanin A, Gilissen LJWJ, Schaart JG, et al. CRISPR/Cas9 Gene Editing of Gluten in Wheat to Reduce Gluten Content and Exposure-Reviewing Methods to Screen for Coeliac Safety. Front Nutr. 2020;7:51. Published 2020 Apr 24. doi:10.3389/fnut.2020.00051