Researchers “create” hypoallergenic cats using CRISPR

What is “Fel d 1”, the main allergenic protein in cats?

Cat hair allergy is an inflammatory immune reaction that occurs when a susceptible person is in the presence of a cat. This allergic reaction can occur immediately or several times, a few hours after contact with the feline. The allergic person then experiences various symptoms such as coughing, breathing problems that can lead to asthma attacks, sneezing, itching, nasal congestion and a feeling of conjunctivitis in the eyes. Not everyone with a cat hair allergy reacts the same way. Sensitivity is different and is a function of environmental and genetic factors.

>> Read also: Cat Allergy: A New Therapeutic Approach?

When the allergic subject comes in contact with a cat, its immune system will produce antibodies called immunoglobulins E whose function is to detect and destroy allergens. These antibodies then trigger an essential immune response, but it is too excessive in people with allergies. A molecule, called histamine, is synthesized in large quantities by certain cell types such as basophilic granulocytes and mast cells. Histamine will cause dilation of small blood vessels called capillaries, increase bronchial contraction, and speed up heart rate. It is also responsible for itching or itching of the skin.

In fact, it is not the cat that causes the allergy, but a particular protein produced in the saliva and tears of the animal that it deposits in its fur when the fur is cleaned by licking. A certain amount is also produced by the skin of the feline at the level of its sebaceous glands. This allergenic protein called Fel d 1 is encoded by the cat’s CH1 and CH2 genes. Other proteins such as Fel d 4, Fel d 3 and Fel d 2 are also allergenic, but appear to be less “active”.

Researchers have “deleted” a region encoding genetic modification

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The method of making hypoallergenics in cats seems simple. Delete the DNA region encoding the “Fel d 1” protein!

The “Fel d 1” protein produced by cats is therefore found in the fur of cats and clings to the hair, so it spreads in the house when the animal loses its hair. Therefore, sensitive people can experience allergy symptoms even if a cat is not in a room by simply touching their hair.

Researchers behind their work analyzed the DNA of about 50 domestic cats and discovered particular regions in the CH1 and CH2 genes encoding the Fel d 1 protein. wild, that these particular regions show great value. variation between species.

This interesting finding allows scientists to determine that the genes encoding the Fel d 1 protein have not been preserved during the evolution of cats. Therefore, this suggests that Fel d 1 is not an essential protein for cat life. which, therefore, can be suppressed without causing harmful effects.

Although a protein close to Fel d 1 has been discovered in mice, it is not present in any other animal. This observation reinforces the researchers’ idea that this protein is not essential. To remove the genes responsible for the synthesis of the Fel d 1 protein, the researchers used the gene editing technique.

>> Read also: Allergies: this is transmitted from mother to child during pregnancy

CRIPR: the gene editing technique

It is a molecular biology technique that cuts DNA using enzymes called restriction endonucleases or, more simply, restriction enzymes. These molecules function as “molecular scissors” by cutting DNA in specific places.

DNA cutting is not done randomly, but in very specific places called specific places. In the case of the CH1 and CH2 genes encoding the “Fel d 1” protein, the principle is to remove the piece of DNA containing these genes and re-solder the whole by homologous recombination. To perform DNA cleavage, different restriction endonucleases are available and can be used. Each restriction endonuclease is specific to a very specific area of ​​the DNA strand and only “cuts” at that location. There are also synthetic restriction endonucleases such as the TALEN system (transcription activator-like effector nucleases).

As part of this research work on hypoallergenic cats, American scientists used CRISPR gene editing technology to remove the coding regions of the “Fel d 1” protein from the cat’s DNA.

What is CRISPR-Cas9?

Called CRISPR-Cas9, this technique was developed by two French researchers, Emmanuelle Charopentier and Jennifer Doudna, who also received the 2020 Nobel Prize in Chemistry for this discovery.

CRISPR means Short palindromic repetitions grouped regularly between spaces and Cas9 is the name of a protein. In this fast-paced, easy-to-use system, RNA (ribonucleic acid) guides the Cas9 protein to the location of the DNA to be cut. Cas9 is an amazing protein that is capable of cutting any part of DNA anywhere. To achieve this, you simply need to be properly guided by attaching an RNA strand corresponding to the DNA to be cut.

This amazing technique works in less than a week, while before it sometimes took several months, regardless of the animal, plant or bacterial species.

>> Read also: CRISPR / Cas9: the lethal weapon of gene therapy

Research into the removal of the Fel 1 d protein is still in its infancy, and scientists have yet to perfect the technique, but are convinced that cats will be completely hypoallergenic.

>> Read also: How the cat conquered the world … and domesticated us

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Source: Nicole F. Brackett, Brian W. Davis, Mazhar Adli, Anna Pomés and Martin D. Chapman, “Evolutionary Biology and Gene Editing of Cat Allergen, Fel d 1”, The CRISPR magazinePublished online: March 28, 2022, https://doi.org/10.1089/crispr.2021.0101

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