Cats are wonderful. My favourites are the really large ones on the savannah, whose predawn roar signals a new day in Africa. Smaller cats are friendlier, but for the ten to twenty percent of us with cat allergies, come with a different set of challenges. Sneezing, watery eyes and in some cases asthma can quickly ruin a social event – all it takes is for Mr Whiskers to enter the room. Luckily for myself and my fellow sufferers, science may have a solution – and it all begins with a hypoallergenic cat named Alsik. That’s right, he’s allergen-free.
A team of scientists has produced the world’s first genetically modified house cat that doesn’t trigger an allergic reaction in humans. The group, based at Gyeongsang National University in South Korea, published their findings in Scientific Reports in 2024 1. The team used gene-editing technology to delete both copies of the CH2 gene from a domestic cat. CH2 is one of two genes that encode the Fel d 1 protein, the allergen found in feline saliva and skin responsible for 90% of cat allergies in humans.
The cat glitter problem
The Fel d 1 protein is just like glitter – it gets everywhere and is virtually impossible to get rid of. It floats around in the air and can lurk on household surfaces for months. Scientists aren’t sure of its exact role in cats, but it may serve as a pheromone-like communication system between individuals – the business card of the cat world. Breeders have attempted to reduce cat glitter through selective breeding, and breeders claim to have produced several lines of hypoallergenic cats. Siberians, Balinese and Russian Blue breeds have lower levels of the protein, but no one has yet eliminated it.
The researchers, led by Professor Il-Keun Kong, used CRISPR-Cas9 gene-editing technology to delete one of the two genes that encode the Fel d 1 protein. CRISPR, the Nobel-Prize winning technology, acts as molecular scissors to edit the great big encyclopedia that is an entire genome. Scientists can adapt it to fix “typos” in the DNA, or add or delete whole “words” from the code. In this case, Professor Kong’s team deleted an entire paragraph from the cat genome.
Dim the lights, put on soft music
The group treated twenty feline embryos with the gene-editing technology and implanted them back into surrogate cat mothers. Two kittens were born, a female named Haemi, and a male named Heavy. Haemi was a heterozygote – she had the gene deletion on one of her chromosomes and a normal copy on the second. Heavy was a little more complicated – he was a mosaic. The gene edit must have occurred in him as a multicellular embryo as some of his tissues showed the gene deletion whilst others were normal. The question was: would he be able to pass the genetically altered form of himself on to his offspring?
Time passed, and feline feelings being what they are, Haemi found herself pregnant courtesy of Heavy. She produced a litter of four kittens, and the team analyzed the newborns’ genetic makeup to see if at least one of them had inherited the gene deletion on both chromosomes. Under normal conditions, there would be a 1 in 4 chance that a kitten would have inherited two deleted gene copies, one from each parent – but Heavy’s mosaicism had lowered the odds of that. Fortunately, Heavy had passed on his gene deletion to one of the offspring, as had the female Haemi. They had produced a single homozygous double mutant missing both copies of the CH2 gene – they called him Alsik.
Soap suds and science
The team set out to see whether Alsik could produce Fel d 1 protein in his saliva – but first they had to deglitter him. To howls of feline fury, Alsik received a bath, with hypoallergenic soap. Cats are meticulous groomers, not just of themselves but of others too. The team needed to remove any trace of his mother’s protein from him before proceeding. Domestic cats typically have 16 µg/ml of Fel d 1 on them, while Alsik before the scrub had just 5 µg/ml. Once the suds had subsided, his glitter was down to less than 1% of the typical cat load. After several weeks of solitary living, Alsik had almost undetectable levels of the protein in his saliva and on his skin – he could not produce the allergen. Alsik was the world’s first glitter-free, truly hypoallergenic cat.
Copy cat
The scientists cloned Alsik to see if an identical twin would share the same features as he did. In due course, Alsik C was born to a surrogate mother and, once grown, subjected to the same tub scrub. Like his older twin, Alsik C showed dramatically reduced levels of Fel d 1, an encouraging sign that the new double-mutation was stable in the cat lineage.
CRISPR-Cas9 technology is a precision technology, but occasionally it can go awry. The results can lead to unwanted editing in the far-flung regions of the genome and occasionally cause chromosomal rearrangements. To eliminate this possibility of influencing the results, Alsik and Alsik C had their complete genomes sequenced. Results confirmed both cats were genetically identical and that no off-target effects had occurred.
Are Hypoallergenic Cats The Way Forward?
This research is not about the novelty of designer pets in our homes. For some folk, cat allergies are more than an inconvenience- they rank second only to dust mites as a cause of respiratory allergies and can trigger severe, even life-threatening, asthma attacks.
The ultimate goal of the research is to develop a gene deletion therapy that could be given to any domestic cat who chooses to live with a sensitized human. Future work includes clinical trials to ensure the safety and well-being of the gene-edited animals. Developing glitter-free female felines will be central to increasing the trial population. Not all cats would need gene therapy – but given the prevalence of cat allergies, there should be a significant market for people who want to enjoy the benefits of pet ownership without the side effects.
One member of the cat population who might pass on gene-editing stares impassively back at me in the cool African dawn. We are separated by twenty feet and the camp’s electric fence. I wonder, does the king of the savannah have cat glitter too? I decided not to find out.
Reference
Lee, S.R., Lee, KL., Song, SH. et al.Generation of Fel d 1 chain 2 genome-edited cats by CRISPR-Cas9 system. Sci Rep 14, 4987 (2024).
Cats are wonderful. My favourites are the really large ones on the savannah, whose predawn roar signals a new day in Africa. Smaller cats are friendlier, but for the ten to twenty percent of us with cat allergies, come with a different set of challenges. Sneezing, watery eyes and in some cases asthma can quickly ruin a social event – all it takes is for Mr Whiskers to enter the room. Luckily for myself and my fellow sufferers, science may have a solution – and it all begins with a hypoallergenic cat named Alsik. That’s right, he’s allergen-free.
A team of scientists has produced the world’s first genetically modified house cat that doesn’t trigger an allergic reaction in humans. The group, based at Gyeongsang National University in South Korea, published their findings in Scientific Reports in 2024 1. The team used gene-editing technology to delete both copies of the CH2 gene from a domestic cat. CH2 is one of two genes that encode the Fel d 1 protein, the allergen found in feline saliva and skin responsible for 90% of cat allergies in humans.
The cat glitter problem
The Fel d 1 protein is just like glitter – it gets everywhere and is virtually impossible to get rid of. It floats around in the air and can lurk on household surfaces for months. Scientists aren’t sure of its exact role in cats, but it may serve as a pheromone-like communication system between individuals – the business card of the cat world. Breeders have attempted to reduce cat glitter through selective breeding, and breeders claim to have produced several lines of hypoallergenic cats. Siberians, Balinese and Russian Blue breeds have lower levels of the protein, but no one has yet eliminated it.
The researchers, led by Professor Il-Keun Kong, used CRISPR-Cas9 gene-editing technology to delete one of the two genes that encode the Fel d 1 protein. CRISPR, the Nobel-Prize winning technology, acts as molecular scissors to edit the great big encyclopedia that is an entire genome. Scientists can adapt it to fix “typos” in the DNA, or add or delete whole “words” from the code. In this case, Professor Kong’s team deleted an entire paragraph from the cat genome.
Dim the lights, put on soft music
The group treated twenty feline embryos with the gene-editing technology and implanted them back into surrogate cat mothers. Two kittens were born, a female named Haemi, and a male named Heavy. Haemi was a heterozygote – she had the gene deletion on one of her chromosomes and a normal copy on the second. Heavy was a little more complicated – he was a mosaic. The gene edit must have occurred in him as a multicellular embryo as some of his tissues showed the gene deletion whilst others were normal. The question was: would he be able to pass the genetically altered form of himself on to his offspring?
Time passed, and feline feelings being what they are, Haemi found herself pregnant courtesy of Heavy. She produced a litter of four kittens, and the team analyzed the newborns’ genetic makeup to see if at least one of them had inherited the gene deletion on both chromosomes. Under normal conditions, there would be a 1 in 4 chance that a kitten would have inherited two deleted gene copies, one from each parent – but Heavy’s mosaicism had lowered the odds of that. Fortunately, Heavy had passed on his gene deletion to one of the offspring, as had the female Haemi. They had produced a single homozygous double mutant missing both copies of the CH2 gene – they called him Alsik.
Soap suds and science
The team set out to see whether Alsik could produce Fel d 1 protein in his saliva – but first they had to deglitter him. To howls of feline fury, Alsik received a bath, with hypoallergenic soap. Cats are meticulous groomers, not just of themselves but of others too. The team needed to remove any trace of his mother’s protein from him before proceeding. Domestic cats typically have 16 µg/ml of Fel d 1 on them, while Alsik before the scrub had just 5 µg/ml. Once the suds had subsided, his glitter was down to less than 1% of the typical cat load. After several weeks of solitary living, Alsik had almost undetectable levels of the protein in his saliva and on his skin – he could not produce the allergen. Alsik was the world’s first glitter-free, truly hypoallergenic cat.
Copy cat
The scientists cloned Alsik to see if an identical twin would share the same features as he did. In due course, Alsik C was born to a surrogate mother and, once grown, subjected to the same tub scrub. Like his older twin, Alsik C showed dramatically reduced levels of Fel d 1, an encouraging sign that the new double-mutation was stable in the cat lineage.
CRISPR-Cas9 technology is a precision technology, but occasionally it can go awry. The results can lead to unwanted editing in the far-flung regions of the genome and occasionally cause chromosomal rearrangements. To eliminate this possibility of influencing the results, Alsik and Alsik C had their complete genomes sequenced. Results confirmed both cats were genetically identical and that no off-target effects had occurred.
Are Hypoallergenic Cats The Way Forward?
This research is not about the novelty of designer pets in our homes. For some folk, cat allergies are more than an inconvenience- they rank second only to dust mites as a cause of respiratory allergies and can trigger severe, even life-threatening, asthma attacks.
The ultimate goal of the research is to develop a gene deletion therapy that could be given to any domestic cat who chooses to live with a sensitized human. Future work includes clinical trials to ensure the safety and well-being of the gene-edited animals. Developing glitter-free female felines will be central to increasing the trial population. Not all cats would need gene therapy – but given the prevalence of cat allergies, there should be a significant market for people who want to enjoy the benefits of pet ownership without the side effects.
One member of the cat population who might pass on gene-editing stares impassively back at me in the cool African dawn. We are separated by twenty feet and the camp’s electric fence. I wonder, does the king of the savannah have cat glitter too? I decided not to find out.
Reference
Lee, S.R., Lee, KL., Song, SH. et al.Generation of Fel d 1 chain 2 genome-edited cats by CRISPR-Cas9 system. Sci Rep 14, 4987 (2024).
