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Researchers Genetically Alter Hens To Produce Allergy-free Eggs

  • Egg allergies are common and are often difficult to deal with, leading to a range of unpleasant symptoms.
  • One area of interest is how to alter the genetics of hens to remove proteins from eggs that cause allergies.
  • A​ recent study found that removing the allergen protein ovomucoid from eggs made them appear safe for consumption, though further testing is needed.
  • Allergies occur when the body has a negative or abnormal reaction to a foreign substance.

    Egg allergies are common and may develop during early childhood, resulting in unpleasant symptoms and leading to negative health outcomes.

    The allergen protein ovomucoid is responsible for many of the allergic responses people with egg allergies experience. Now, genetic specialists may be able to eliminate an egg allergy at its source.

    A​ recent study published in Food and Chemical Toxicology explored the possibility of altering the genetics of hens to remove ovomucoid from eggs.

    The researchers found the method they used produced eggs that may be safe for specific uses among people with egg allergies.

    People with egg allergies can experience a variety of reactions, including vomiting, diarrhea, or rash. Severe egg allergies may even trigger life threatening anaphylactic reactions.

    A​ person with an egg allergy should try to avoid consuming eggs, but this can be challenging. Many products contain eggs, so parents and people of all ages must carefully read food labels and be extra vigilant to ensure that foods don't have eggs in them.

    Egg allergies could be stressful for anyone — and some children may worry about being different from their peers. In some cases, children may grow out of egg allergies as they age.

    N​on-study author and general practitioner Dr. Blen Tesfu, a medical advisor at Welzo, explained to Medical News Today:

    "Egg allergies are relatively common, particularly in children. They are most often caused by an allergic reaction to proteins found in egg whites, such as ovalbumin or ovomucoid. The impact of egg allergies can extend beyond dietary restrictions. Eggs are widely used in various food products, including baked goods, sauces, dressings, and processed foods, making it necessary for individuals with egg allergies to carefully read ingredient labels and avoid foods that contain eggs or egg-derived ingredients."

    Researchers of the current study sought to help people with egg allergies. They hypothesized that by removing the protein that causes the allergic reaction, you could create an allergy-free egg. These eggs could, therefore, be safer for people with egg allergies to consume.

    The particular protein they were studying was ovomucoid, which is responsible for many egg allergies. Researchers investigated how genetically edited hens could produce ovomucoid-free eggs.

    Their method utilized transcription activator-like effector nucleases (TALENs). These proteins aid in the cutting and, thus, alteration of DNA. Researchers removed the ovomucoid gene in two chicken strains. They then tested the produced eggs for safety.

    Researchers found that the eggs from genetically altered hens did not have ovomucoid or mutations of ovomucoid. Their findings indicate the safety of these eggs as a creation that removes major allergy concerns.

    Study author Ryo Ezaki, assistant professor at the Graduate School of Integrated Sciences for Life at Hiroshima University, Japan, explained in a news release:

    "These results indicate the importance of safety evaluation and reveal that the eggs laid by this OVM [ovomucoid] knockout chicken solve the allergy problem in food and vaccines. The next phase of research will be to evaluate the physical properties and processing suitability of OVM [ovomucoid] knockout eggs and to confirm their efficacy through clinical trials."

    D​r. Tesfu noted what the new research could mean for people with egg allergies:

    "For individuals with severe egg allergies, even trace amounts of egg in food or vaccines can trigger severe allergic reactions. With the development of OVM-knockout chickens, these individuals may be able to consume eggs and egg-derived products without fear of an allergic reaction. This could dramatically expand their dietary options and reduce anxiety around food. Moreover, since eggs are used in the production of certain vaccines (such as some types of flu vaccines), this development could potentially make these vaccines safer for people with egg allergies."

    W​e likely won't see allergy-free egg-containing products on grocery store shelves yet. Experts may need to do further testing in this area to ensure safety.

    The researchers acknowledge that based on the full analysis, people who experience an allergic reaction to small amounts of ovomucoid could still experience a reaction or problems.

    But researchers think these ovomucoid-null eggs could be safely used in heat-processed foods among people with egg allergies.

    Agencies would also have to decide how to warn consumers about genetically altered products. Dr. Tesfu explained:

    "The introduction of these eggs into the food supply would need to be carefully managed, given potential consumer concerns about genetically modified organisms (GMOs). Thorough and transparent safety evaluations, as noted in the study, would be crucial in gaining public acceptance. Finally, while these results are promising, more research is likely needed to understand the full implications and potential side effects of this genetic modification on the chickens themselves and the broader ecosystem."

    However, the results demonstrate another practical application of gene editing that may ultimately lead to the public reaping significant benefits.

    Non-study author Eric Kmiec, PhD, executive director and chief scientific officer of ChristianaCare's Gene Editing Institute told MNT:

    "This study represents a step forward in the clinical application of gene editing. Using a gene editing tool, TALENs, the less well-known cousin of the famous CRISPR complex, Ezaki et al demonstrate that deletion of a key allergen can be carried out with a high degree of safety. What I find most refreshing about the study is that the work is carried out with great care presenting foundational data upon which a clinical application can no doubt be built."


    Egg-Citing Breakthrough: Scientists Develop Allergy-Free Eggs

    Brown Eggs

    Researchers have created a genetically modified chicken egg, known as the OVM-knockout, which lacks the ovomucoid protein that causes egg white allergies, using genome-editing tools called TALENs. Initial safety evaluations of these eggs show no off-target mutations in protein-coding regions and no evidence of the allergy-causing protein, paving the way for further research and potential use in food and vaccines for individuals with egg allergies.

    Scientists have successfully engineered a chicken egg that could potentially be safe for consumption by individuals with egg white allergies. Allergies to chicken eggs are among the most prevalent allergies in children. While the majority of children tend to outgrow this allergy by the age of 16, some continue to be allergic to eggs into adulthood. Symptoms of egg white allergies range from vomiting and stomach cramps to breathing difficulties, hives, and swelling. This allergy can also prevent some individuals from getting certain flu vaccinations.

    Leveraging genome editing technology, the scientists were able to create an egg devoid of the protein responsible for triggering egg white allergies. This protein, known as ovomucoid, makes up about 11% of all protein found in egg whites.

    Research detailing the food safety profile of this modified egg, called the OVM-knockout, was detailed in a paper published in Food and Chemical Toxicology in April 2023.

    "To use OVM-knockout chicken eggs as food, it is important to evaluate their safety as food. In this study, we examined the presence or absence of mutant protein expression, vector sequence insertion, and off-target effects in chickens knocked out with OVM by platinum transcription activator-like effector nucleases (TALENs)," said Ryo Ezaki, an assistant professor at the Graduate School of Integrated Sciences for Life at Hiroshima University in Hiroshima, Japan.

    TALENs are restriction enzymes that recognize specific DNA sequences and break or cut them.

    OVM Knocked Out Chickens

    Scientists from Hiroshima University produced OVM knocked out chickens using genome editing tools. (Colored chickens are knockout chickens.) Credit: Ezaki et al. 2023, Food and Chemical Toxicology

    In order to develop the OVM-knockout eggs, researchers needed to detect and eliminate the ovomucoid protein in the egg whites. TALENs were engineered to target a piece of RNA called exon 1, which codes for specific proteins. The eggs produced from this technique were then tested to ensure there was no ovomucoid protein, mutant ovomucoid protein, or other off-target effects.

    The eggs had the desired frameshift mutation, which is a mutation created by inserting or deleting nucleotide bases in a gene, and none of them expressed mature ovomucoid proteins. Anti-ovomucoid and anti-mutant ovomucoid antibodies were used to detect any traces of the protein, but there was no evidence of ovomucoid in the eggs. This means that mutant ovomucoids could not create new allergens. This is an important step in determining the safety profile of the eggs.

    Other gene editing tools, such as CRISPR, tend to have off-target mutagenesis effects. This means that new mutations are prompted by the gene editing process. However, whole genome sequencing of the altered egg whites showed mutations, which were possibly off-target effects, were not localized to the protein-coding regions.

    "The eggs laid by homozygous OVM-knockout hens showed no evident abnormalities. The albumen contained neither the mature OVM nor the OVM-truncated variant," said Ezaki. "The potential TALEN-induced off-target effects in OVM-knockout chickens were localized in the intergenic and intron regions. Plasmid vectors used for genome editing were only transiently present and did not integrate into the genome of edited chickens. These results indicate the importance of safety evaluations and reveal that the eggs laid by this OVM knockout chicken solve the allergy problem in food and vaccines."

    Looking ahead, researchers will continue to verify the safety profile of the OVM-knockout eggs. Because some people are highly allergic to this specific protein, even small amounts of ovomucoid can cause a reaction. Researchers will need to perform additional immunological and clinical studies to determine the safety of the OVM-knockout eggs. At this time, researchers have determined that OVM-knockout eggs are less allergenic than standard eggs and can be safely used in heat-processed foods that patients with egg allergies can eat.

    "The next phase of research will be to evaluate the physical properties and processing suitability of OVM-knockout eggs, and to confirm their efficacy through clinical trials," said Ezaki. "We will continue to conduct further research toward the practical application of allergy-reduced eggs."

    Reference: "Transcription activator-like effector nuclease-mediated deletion safely eliminates the major egg allergen ovomucoid in chickens" by Ryo Ezaki, Tetsushi Sakuma, Daisuke Kodama, Ryou Sasahara, Taichi Shiraogawa, Kennosuke Ichikawa, Mei Matsuzaki, Akihiro Handa, Takashi Yamamoto, and Hiroyuki Horiuchi, 6 March 2023, Food and Chemical Toxicology.DOI: 10.1016/j.Fct.2023.113703

    The study was funded by the Japan Society for the Promotion of Science and the Japan Science and Technology Agency.


    Scientists Create OVM-knockout Egg, Allergy-free And Safe For All

    The eggs produced were then tested for the absence of ovomucoid protein, its mutant proteins, and other off-target effects.

    The team observed that these engineered eggs exhibited frameshift mutation – mutation created by inserting or deleting nucleotide bases in a gene as desired.

    Further testing using anti-ovomucoid and anti-mutant ovomucoid antibodies confirmed the lack of any traces of the allergen protein, confirming the eggs to be safe.

    "The eggs laid by homozygous OVM-knockout hens showed no evident abnormalities. The albumen contained neither the mature OVM nor the OVM-truncated variant," Ezaki said. "The potential TALEN-induced off-target effects in OVM-knockout chickens were localized in the intergenic and intron regions. Plasmid vectors used for genome editing were only transiently present and did not integrate into the genome of edited chickens. These results indicate the importance of safety evaluations and reveal that the eggs laid by this OVM knockout chicken solve the allergy problem in food and vaccines."

    The research, supported by the Japan Society for the Promotion of Science KAKENHI, will continue to verify the safety profile of allergy-free eggs. Ovomucoid is potent, with tiny traces setting off reactions. Although it is determined at this phase that OVM-knockout eggs are less allergenic than standard eggs and are safe for use in heat-processed foods without any threat of triggering allergies, the team will further analyze their physical properties and processing suitability and confirm efficacy through clinical trials.






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