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Gene-edited dogs created from cloned skin cells for the first time

New gene-editing approach could be used to eliminate disease-causing mutations from pedigree dog breeds or even from clones of individual dogs
Two beagle puppies
Gene-edited beagle puppies
MKbiotech/Chungnam National University

Two beagle dogs have been born in South Korea from cloned skin cells altered by CRISPR gene editing. CRISPR-edited dogs have previously been created by altering fertilised eggs, but this is the first time they have been created by cloning.

Many pure-bred pedigree dogs have disease-causing mutations. Gene editing could be used to eliminate these without affecting other traits. So, for this purpose, the cloning approach has advantages over the editing-eggs approach, says Okjae Koo at biotech company ToolGen.”[It] is more reliable for generating various pure-bred genome-edited dogs,” says Koo.

To create the cloned puppies, Koo and his colleagues first gene-edited skin cells to mutate a gene called DJ-1 and prevent the protein it codes for from being made. Mutations in DJ-1 are associated with diseases such as ʲ쾱ԲDz’s, so studying dogs that lack the DJ-1 protein could help develop treatments for these conditions.

In addition to knocking out DJ-1, the team added several genes, including one for a fluorescent green protein called GFP. This was done to make it easier to detect which cells had been successfully edited, but the team doesn’t plan to add these genes in future studies, says Koo.

The team then placed these cells next to egg cells whose DNA had been removed. Each skin cell and empty egg cell were fused together by short pulses of electricity, and the resulting embryos implanted in a surrogate mother.

At the age of 22 months, the two dogs are healthy and don’t have any abnormalities – though their skin does glow green in ultraviolet light. Since diseases linked to DJ-1 are age-related, the dogs might develop issues as they get older.

Altogether, 68 embryos were transferred into six dogs, resulting in two puppies. That is a success rate of around 3 per cent – similar to that achieved by  at the Guangzhou Institutes of Biomedicine and ҹ1000 in China when his team , a feat they revealed in 2015.

Those dogs, called Tiangou and Hercules, are beagles that have more muscle mass than normal due to a gene deletion. “Both Tiangou and Hercules are fine,” says Lai. His team has since created several other dogs using the same method, he says.

Two beagles
The cloned dogs are healthy at 14 months
MKbiotech/Chungnam National University

Lai agrees that the cloning technique used by the team in South Korea does have advantages. When fertilised eggs are gene edited, the resulting animals are usually chimeras, meaning some of their cells are gene edited but others aren’t. That means further breeding is needed to create dogs whose cells all have the desired change, says Lai. With the cloning technique, no further breeding is necessary.

Both Lai and Koo’s teams are creating dogs for medical research. However, cloning is also increasingly being used to create copies of beloved pets that have died, using tissue samples taken soon afterwards.

In the US, a company called has so far created about 1000 “cloned companion animals”, a spokesperson told New Scientist. ViaGen charges $50,000 for cloning a dog and $38,000 for a cat.

Cloning could be combined with gene editing to make these animals healthier. ViaGen doesn’t currently offer any kind of genetic modification or editing, but hasn’t ruled out doing so in the future. “We are willing to consider all proven options that are approved by necessary regulatory agencies, good for animals and meet a need for society,” the spokesperson said.

BMC Biotechnology

Topics: CRISPR / Dogs / Genetics