Gene editing may enable allergen-free cats for allergic pet owners

PHOENIX — Sensitized pet lovers may see respiratory relief as scientists have targeted an allergenic protein to delete from cat DNA, according to a study presented at the American Academy of Allergy, Asthma & Immunology Annual Meeting.

“We’re trying to use CRISPR gene editing to edit out the major allergen from cats, so that means you could have an allergen-free cat,” Nicole F. Brackett, PhD, senior scientist at INDOOR Biotechnologies told Healio.

By examining 136 publicly available exotic cat genomes across 38 species in the National Center for Biotechnology Information’s sequence read archive database, the researchers performed a bioinformatics analysis to determine the evolution and functional significance of the major cat allergen Fel d 1.

“The exotic cats I looked at ranged from cats in the same genus as domestic cats all the way to lions, tigers and the Panthera species that diverge from domestic cats up to 11 million years ago,” Brackett said.

Two chains, chain 1 and chain 2, code for Fel d 1. Chain 2 is more variable than chain 1.

“But interestingly, the protein sequences were more variable than the DNA sequences, which was surprising. Normally, you would expect the protein to be more conserved than the DNA. We saw the exact opposite,” Brackett said.

The researchers also found up to 90 different unique amino acid substitutions across all the different cats they examined and mapped them on to the recombinant structure of Fel d 1.

“Oftentimes we’re asked the question, ‘Is the allergen conserved?’ And if it’s conserved, that could mean it’s essential to cats. If we’re trying to eventually use CRISPR to map out the major allergen in cats, if it were something that’s essential, that could be detrimental to the cat,” Brackett said.

“The nice thing about this study is it’s showing us it doesn’t look like the allergen is conserved. There’s a lot of variability and a lot more than what we would expect per a traditionally conserved protein,” she continued.

Because Fel d 1 does not appear to be essential, the researchers concluded, it is a viable and appropriate target that could be deleted with gene editing.

“It could mean an allergen-free cat, which would be amazing for a cat-allergic patient who wants a cat,” Brackett said.

Ideally, the researchers said the treatment would be applied to adult cats.

“From an ethics standpoint, and even from a marketing standpoint, I think that’s what most people would prefer,” she said.

Scientifically, however, Brackett said it would be easier to perform this editing at the germline level during the embryo stage. Once these cats are born and grown, they could be bred, passing on their nonallergenic properties to the next generation.

“Ideally, that’s not what we would like to do. But I think the limiting factors right now, which are the limiting factors in CRISPR in general, are delivery mechanisms for delivering CRISPR reagents to adult animals outside of things like the blood, liver or eye, which are relatively easier to target,” Brackett said.

The researchers now are compiling their data and expect to publish it soon.

“The next step for the science is then going to be trying to do the knockout potentially at the embryo stage,” Brackett said. “We’ve shown proof of principle of the knockout in vitro at the cellular stage, and that paper is going to be published in April.”