A team of scientists from Chungnam National University in Korea recently used a system based on CRISPR gene editing to correct a mutation related to canine hip dysplasia in Labrador retriever dogs. Two dogs were cloned from another dog who had the disease. The experiment was a success, and the dogs were born with the mutation corrected.
Canine hip dysplasia is a common and extremely painful disease that is difficult to treat. It’s caused by an interaction between environmental and genetic factors. The disease is usually found in large- and medium-sized dogs. Purebred dogs, in particular, are susceptible to genetic disorders because of the many years of inbreeding.
The scientists used prime editing, which is a new form of genomic editing that is more precise, simpler, and efficient than traditional CRISPR gene editing. Prime editing has been used in human cells and also used to develop genetically altered plants, mice, and fruit flies, but this is the first time, as far as the scientists are aware, that the technique has been used in dogs.
Unlike traditional CRISPR gene editing, which has to be performed at a certain stage in the cell division cycle, prime editing can be done at any stage. Also, unlike CRISPR editing, prime editing does not require a donor DNA template.
Prime editing makes a nick in a single strand of DNA, in contrast to traditional CRISPR gene editing, which uses an enzyme to cut through both strands. Prime editing then uses reverse transcriptase to create accurate changes in the target sequence.
The scientists collected somatic (non-reproductive) cells from a dog that had been diagnosed with hip dysplasia. They used prime editing to correct a single mutation in the cells. Then, they used somatic cell nuclear transfer (SCNT) to fuse the genetically edited DNA from the somatic cells with oocytes in the lab.
The resulting embryos were transferred into dogs that served as surrogate mothers. Two puppies were born. The experiment was successful in changing the targeted mutation and not creating any additional unwanted mutations. The dogs are still puppies, so it’s too early to tell how well the genetic alterations will prevent them from developing hip dysplasia.
In this study, a single mutation was genetically altered. However, there are multiple mutations that are associated with canine hip dysplasia. The scientists involved in this study consider it a starting point and plan to do more studies that will correct other mutations. In this way, they hope to better understand the relationship of each individual mutation to the disease by testing the effect that each change has on the symptoms of hip dysplasia, including the dogs’ behavior, gait, and mobility.
These studies are likely to have applications to human disease. Human hip dysplasia is very similar to canine hip dysplasia. What scientists learn from these gene editing studies in dogs may be very helpful in increasing our understanding of the disease as it occurs in humans.
The applications may also go beyond this specific disease. Prime editing may be a useful tool for creating dog models that can be used to study other human diseases as well.
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