Preprint / Version 1

The Applications of RNAi and CRISPR Gene Editing Technologies to Decrease Immunodominant Allergens in Foods

##article.authors##

  • Asher Boorstein High School Student

DOI:

https://doi.org/10.58445/rars.926

Keywords:

RNAi, CRISPR, Immunodominant Allergens, Food allergies

Abstract

Food allergies have become a critical health problem worldwide. This disease state can be associated with potential mortality from anaphylactic reactions. The economic cost for individuals living with food allergies and their caregivers is significant and increasing. The most common approaches to manage food allergies are the avoidance of the food trigger(s) and use of epinephrine for anaphylactic reactions. Overall, there are limited therapeutic interventions available for this population. A new field in food allergy management has emerged based upon gene editing (CRISPR) and gene silencing (RNAi) technologies. These technologies could potentially reduce allergenicity of a food by altering the specific food’s major allergen genes or interfering with the transcription of those genes. This review paper summarizes 7 primary research papers that utilized either CRISPR or RNAi to reduce the allergenicity of foods reported to cause allergic reactions. For all studies presented in this review, there was a significant decrease in the immunodominant allergen gene products for the transgenic plants compared to wild type varieties. Some of the studies were able to compare the difference in allergenicity of the altered food product compared to control, noticing similarities and differences in the phenotypes of both groups as well as major decrease in immunodominant allergen genes. One of the 7 studies performed an in vivo skin prick test showing decreased reactivity with the transgenic plant sample compared to wild type varieties. This review discusses the immune mechanisms underlying food allergies, the functions of the gene editing and silencing technologies, the implication of the technologies on food allergies, and future steps for treating food allergy with gene editing/silencing technologies.

References

Ahammer L, Grutsch S, Kamenik AS, Liedl KR, Tollinger M. Structure of the Major Apple Allergen Mal d 1, 2017. J Agric Food Chem. 65(8): 1606-1612. doi: 10.1021/acs.jafc.6b05752.

Calvani M, Anania C, Cuomo B, D'Auria E, Decimo F, Indirli GC, Marseglia G, Mastrorilli V, Sartorio MUA, Santoro A, Veronelli E, 2021. Non-IgE- or Mixed IgE/Non-IgE-Mediated Gastrointestinal Food Allergies in the First Years of Life: Old and New Tools for Diagnosis. Nutrients. 13(1): 226. doi: 10.3390/nu13010226.

Camerlengo F, Fritelli A, Sparks C, Doherty A, Martignago D, Larré C, Lupi R, Sestilli F, Masci S, 2020. CRISPR-Cas9 Multiplex Editing of the a-Amylase/Trypsin Inhibitor Genes to Reduce Allergen Proteins in Durum Wheat. Front. Sustain. Food Syst. 4: 104. doi: 10.3389/fsufs.2020.00104

Cardona V, Ansotegui IJ, Ebisawa M, El-Gamal Y, Fernandez Rivas M, Fineman S, Geller M, Gonzalez-Estrada A, Greenberger PA, Sanchez Borges M, Senna G, Sheikh A, Tanno LK,

Thong BY, Turner PJ, Worm M, 2020. World allergy organization anaphylaxis guidance. World Allergy Organ J. 13(10): 100472. doi: 10.1016/j.waojou.2020.100472

Cianferoni A, 2020. Non-IgE Mediated Food Allergy. Curr Pediatr Rev. 16(2): 95-105. doi: 10.2174/1573396315666191031103714.

Dodo HW, Konan KN, Chen FC, Egnin M, Viquez OM, 2008. 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. 6(2): 135-145. doi: 10.1111/j.1467-7652.2007.00292.x.

Epstein-Rigbi N, Goldberg MR, Levy MB, Nachshon L, Elizur A, 2019. Quality of Life of Food-Allergic Patients Before, During, and After Oral Immunotherapy. J Allergy Clin Immunol Pract. 7(2): 429-436.e2. doi: 10.1016/j.jaip.2018.06.016.

Epstein-Rigbi N, Levy MB, Nachshon L, Koren Y, Katz Y, Goldberg MR, Elizur A, 2023. Efficacy and safety of food allergy oral immunotherapy in adults. Allergy. 78(3): 803-811. doi: 10.1111/all.15537.

Fire A, Xu S, Montgomery MK, Kostas SA, Driver SE, Mello CC, 1998. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature. 391(6669): 806-811. doi: 10.1038/35888.

Geisslitz S, Weegels P, Shewry P, Zevallos V, Masci S, Sorrells M, Gregorini A, Colomba M, Jonkers D, Huang X, De Giorgio R, Caio GP, D'Amico S, Larré C, Brouns F, 2022. Wheat amylase/trypsin inhibitors (ATIs): occurrence, function and health aspects. Eur J Nutr. 61(6): 2873-2880. doi: 10.1007/s00394-022-02841-y.

Gold MS, Sainsbury R, 2000. First aid anaphylaxis management in children who were prescribed an epinephrine auto injector device (EpiPen). J Allergy Clin Immunol. 106(1 Pt 1): 171-176. doi: 10.1067/mai.2000.106041.

Gupta R, Holdford D, Bilaver L, Dyer A, Holl JL, Meltzer D, 2013. The Economic Impact of Childhood Food Allergy in the United States. JAMA Pediatr. 167(11): 1026–1031. doi:10.1001/jamapediatrics.2013.2376

Gupta RS, Warren CM, Smith BM, Jiang J, Blumenstock JA, Davis MM, Schleimer RP, Nadeau KC, 2019. Prevalence and Severity of Food Allergies Among US Adults. JAMA Netw Open. 2(1): e185630. doi: 10.1001/jamanetworkopen.2018.5630.

Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA, Charpentier EA, 2012 programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science. 337(6096): 816-821. doi: 10.1126/science.1225829.

Kalunke RM, Tundo S, Sestili F, Camerlengo F, Lafiandra D, Lupi R, Larré C, Denery-Papini S, Islam S, Ma W, D'Amico S, Masci S, 2020. Reduction of Allergenic Potential in Bread Wheat RNAi Transgenic Lines Silenced for CM3, CM16 and 0.28ATI Genes. Int J Mol Sci. 21(16): 5817. doi: 10.3390/ijms21165817.

Keet CA, Berin MC, 2022. The year in food allergy. J Allergy Clin Immunol. 149(3): 867-873. doi: 10.1016/j.jaci.2021.12.785.

Knott GJ, Doudna JA, 2018. CRISPR-Cas guides the future of genetic engineering. Science. 361(6405): 866-869. doi: 10.1126/science.aat5011.

Liu S, Chen G, Yang L, Gai J, Zhu Y, 2013. Production of Transgenic Soybean to Eliminate the Major Allergen Gly m Bd 30K by RNA Interference-mediated Gene

Moreno FJ, Clemente A, 2008. 2S Albumin Storage Proteins: What Makes them Food Allergens? Open Biochem J. 2: 16-28. doi: 10.2174/1874091X00802010016.

Motosue MS, Bellolio MF, Van Houten HK, Shah ND, Campbell RL, 2017. Increasing Emergency Department Visits for Anaphylaxis, 2005-2014. J Allergy Clin Immunol Pract. 5(1): 171-175.e3. doi: 10.1016/j.jaip.2016.08.013.

Mulalapele TL, Xi J, 2021. Detection and inactivation of allergens in soybeans: A brief review of recent research advances. Grain Oil Sci Technol. 4(4): 191-200. doi: https://doi.org/10.1016/j.gaost.2021.11.001.

Nowak-Węgrzyn A, Katz Y, Mehr SS, Koletzko S, 2015. Non-IgE-mediated gastrointestinal food allergy. J Allergy Clin Immunol. 135(5): 1114-1124. doi: 10.1016/j.jaci.2015.03.025.

Ontiveros N, Flores-Mendoza LK, Canizalez-Román VA and Cabrera-Chavez F, 2014. Food Allergy: Prevalence and Food Technology Approaches for the Control of IgE-mediated Food Allergy. Austin J Nutri Food Sci. 2(5): 1029. ISSN: 2381-8980.

Osborne NJ, Koplin JJ, Martin PE, Gurrin LC, Lowe AJ, Matheson MC, Ponsonby AL, Wake M, Tang ML, Dharmage SC, Allen KJ; HealthNuts Investigators, 2011. Prevalence of challenge-proven IgE-mediated food allergy using population-based sampling and predetermined challenge criteria in infants. J Allergy Clin Immunol. 127(3): 668-676.e1-2. doi: 10.1016/j.jaci.2011.01.039.

PALISADE Group of Clinical Investigators; Vickery BP, Vereda A, Casale TB, Beyer K, du Toit G, Hourihane JO, Jones SM, Shreffler WG, Marcantonio A, Zawadzki R, Sher L, Carr WW, Fineman S, Greos L, Rachid R, Ibáñez MD, Tilles S, Assa’ad AH, Nilsson C, Rupp N, Welch MJ, Sussman G, Chinthrajah S, Blumchen K, Sher E, Spergel JM, Leickly FE, Zielen S, Wang J, Sanders GM, Wood RA, Cheema A, Bindslev-Jensen C, Leonard S, Kachru R, Johnston DT, Hampel FC Jr, Kim EH, Anagnostou A, Pongracic JA, Ben-Shoshan M, Sharma HP, Stillerman A, Windom HH, Yang WH, Muraro A, Zubeldia JM, Sharma V, Dorsey MJ, Chong HJ, Ohayon J, Bird JA, Carr TF, Siri D, Fernández-Rivas M, Jeong DK, Fleischer DM, Lieberman JA,

Dubois AEJ, Tsoumani M, Ciaccio CE, Portnoy JM, Mansfield LE, Fritz SB, Lanser BJ, Matz J, Oude Elberink HNG, Varshney P, Dilly SG, Adelman DC, Burks AW, 2018. AR101 Oral Immunotherapy for Peanut Allergy. N Engl J Med. 379(21): 1991-2001. doi: 10.1056/NEJMoa1812856.

Palladino C, Breiteneder H, 2018. Peanut allergens. Mol Immunol. 100: 58-70. doi: 10.1016/j.molimm.2018.04.005.

Patel N, Chong KW, Yip AYG, Ierodiakonou D, Bartra J, Boyle RJ, Turner PJ, 2021. Use of multiple epinephrine doses in anaphylaxis: A systematic review and meta-analysis. J Allergy Clin Immunol. 148(5): 1307-1315. doi: 10.1016/j.jaci.2021.03.042.

Pouessel G, Lezmi G, 2023. Oral immunotherapy for food allergy: Translation from studies to clinical practice? World Allergy Organ J. 16(2): 100747. doi: 10.1016/j.waojou.2023.100747.

Sampson HA, Muñoz-Furlong A, Bock SA, Schmitt C, Bass R, Chowdhury BA, Decker WW, Furlong TJ, Galli SJ, Golden DB, Gruchalla RS, Harlor AD Jr, Hepner DL, Howarth M, Kaplan AP, Levy JH, Lewis LM, Lieberman PL, Metcalfe DD, Murphy R, Pollart SM, Pumphrey RS, Rosenwasser LJ, Simons FE, Wood JP, Camargo CA Jr, 2005. Symposium on the definition and management of anaphylaxis: summary report. J Allergy Clin Immunol. 115(3): 584-591. doi: 10.1016/j.jaci.2005.01.009

Sicherer SH, Warren CM, Dant C, Gupta RS, Nadeau KC, 2020. Food Allergy from Infancy Through Adulthood. J Allergy Clin Immunol Pract. 8(6): 1854-1864. doi: 10.1016/j.jaip.2020.02.010.

Stone KD, Prussin C, Metcalfe DD, 2010. IgE, mast cells, basophils, and eosinophils. J Allergy Clin Immunol. 125(2 Suppl 2): S73-80. doi: 10.1016/j.jaci.2009.11.017.

Sugano S, Hirose A, Kanazashi Y, Adachi K, Hibara M, Itoh T, Mikami M, Endo M, Hirose S, Maruyama N, Abe J, Yamada T, 2020. Simultaneous induction of mutant alleles of two allergenic genes in soybean by using site-directed mutagenesis. BMC Plant Biol. 20(1): 513. doi: 10.1186/s12870-020-02708-6.

Tundo S, Lupi R, Lafond M, Giardina T, Larré C, Denery-Papini S, Morisset M, Kalunke R, Sestili F, Masci S, 2018. Wheat ATI CM3, CM16 and 0.28 Allergens Produced in Pichia Pastoris Display a Different Eliciting Potential in Food Allergy to Wheat. Plants (Basel). 7(4): 101. doi: 10.3390/plants7040101.

Turner PJ, Jerschow E, Umasunthar T, Lin R, Campbell DE, Boyle RJ, 2017. Fatal Anaphylaxis: Mortality Rate and Risk Factors. J Allergy Clin Immunol Pract. 5(5): 1169-1178. doi: 10.1016/j.jaip.2017.06.031.

Vazquez-Ortiz M, Turner PJ, 2016. Improving the safety of oral immunotherapy for food allergy. Pediatr Allergy Immunol. 27(2): 117-125. doi: 10.1111/pai.12510.

Warren CM, Jiang J, Gupta RS. 2020. Epidemiology and Burden of Food Allergy. Curr Allergy Asthma Rep. 20(2): 6. doi: 10.1007/s11882-020-0898-7.

Wood RA, Camargo CA, Lieberman P, Sampson HA, Schwartz LB, Zitt M, Collins C, Tringale M, Wilkinson M, Boyle J, Simons FER, 2014. Anaphylaxis in America: The prevalence and characteristics of anaphylaxis in the United States. J Allergy Clin Immunol. 133(2): 461-467. doi: https://doi.org/10.1016/j.jaci.2013.08.016

Yu W, Freeland DMH, Nadeau KC, 2016. Food allergy: immune mechanisms, diagnosis and immunotherapy. Nat Rev Immunol. 16(12): 751-765. doi: 10.1038/nri.2016.111.

Zablotsky B, Black LI, Akinbami LJ. 2023. Diagnosed Allergic Conditions in Children Aged 0-17 Years: United States, 2021. NCHS Data Brief. 2023(459): 1-8. doi: https://dx.doi.org/10.15620/ cdc:122809.

Zhang S, Sicherer S, Berin MC, Agyemang A, 2021. Pathophysiology of Non-IgE-Mediated Food Allergy. Immunotargets Ther. 10: 431-446. doi: 10.2147/ITT.S284821.

Downloads

Posted

2024-01-27

Categories