Scientists and researchers hope to use gene editing to find cures and management methods for common diseases. While gene editing has many potential uses for dogs, it also presents great biomedical possibilities for humans, as well.
Dogs have a disease phenotype very similar to humans, in addition to sharing many of the same metabolic, physiological, and anatomical characteristics. This makes dogs one of the most valuable disease-modeling large mammals available. Of the available gene editing methods, clustered regularly interspaced short palindromic repeat (CRISPR) has produced the best results.
1. Enhancing Specific Traits in Dogs
In 2015, a team of researchers was able to successfully combine the CRISPR-associated (Cas) 9 (“Cas9”) system and an auto-embryo transfer strategy to develop “gene knockout” dog breeds. The team targeted the myostatin (MSTN) gene in beagles, which regulates musculature. Suppressing or removing this gene can cause muscle hypertrophy without severe adverse side effects. Essentially, this study proved that specific genes in dogs can be targeted for removal, suppression, or enhancement.
The researchers themselves stated that the purpose of their work is twofold. The first is to create dogs specifically designed for biomedical research. The second is to create “new strains of dogs with favorable traits for other purposes.” For non-medical applications, this would mean enhancing traits that make certain breeds suited to specific fields such as herding livestock, aiding police and rescue work, and servicing disabled individuals.
A study in 2017 expanded this work. The researchers combined embryo microinjection of CRISPR/Cas9 with somatic cell nuclear transfer (SCNT). This marked the first time that gene targeted dogs were efficiently bred using SCNT, specifically with gene knockouts, gene knock ins, and point mutations. The study was intended to serve as a “general platform” to create gene edited dog breeds more quickly, in a more cost-effective manner.
As a side note, beagles were used in both studies. In addition to being great family dogs, beagles are also one of the most popular breeds for biomedical research.
2. Correcting Genetic Defects in Dogs
There are many dog breeds that suffer from specific genetic diseases. A primary argument in the debate surrounding benefits of mutts over purebreds is that purebreds have so many genetic diseases. Of these, canine hip dysplasia is a common disease in medium and large breeds (limping is one of the main signs). Previously, the only solution was to remove dogs affected by hip dysplasia from breeding lines and surgically correct the disease. However, a 2022 study successfully corrected a genetic mutation related to hip dysplasia in a Labrador Retriever.
This study used prime editing, which is a novel genome editing tool based on the CRISPR method and Cas9 system. The researchers collected cells from a dog with hip dysplasia, used prime editing to correct the mutation, and then bred dogs from the corrected cells using SCNT. Their success provides tentative hope that prime editing can be used to correct genetic defects in dogs, although further research is needed.
The drive to create healthier breeds and solve some of the most pressing genetic diseases is not limited to researchers and scientists, however. Self-described “biohacker” breeders believe that gene editing can be used to remove genetic diseases from purebred lines more quickly than overhauling current breeding practices. For example, in 2017 a kennel operator from Mississippi was attempting to solve hyperuricemia in Dalmatians. He was ultimately shut down by the Food and Drug Administration (FDA), which was in the process of developing regulatory legislation on gene editing for animals.
The FDA formally released legislation on “Intentional Genomic Alternations (IGAs) in Animals” in May 2024. The legislation covers the risk-based regulatory approach and approval process for developing IGAs in animals like dogs. The legislation purportedly supports developing IGAs in animals related to animal health. However, only time will tell whether breeders and enthusiasts seeking to create genetically healthier domestic pets will be approved.
3. Treating Duchenne Muscular Dystrophy in Humans and Dogs
Duchenne Muscular Dystrophy (DMD) is a neuromuscular disease that causes progressive skeletal and muscle weakness. DMD primarily affects males and symptoms often appear during youth aged two to six. Although there is no cure for DMD, a 2018 study proved that genetic editing may be a viable method for managing DMD symptoms in the future.
Researchers used the CRISPR genetic editing method to further damage genes in four dogs with a canine variant of DMD. Although this approach was unusual, it proved initially promising: the further-mutated genes were able to begin producing key muscle proteins. Though subjects did not regain lost muscle function, this method could be useful for preventing symptoms from progressing.
4. Studying Proteins and Protein Deficiencies in Humans and Dogs
More recently in 2022, researchers were able to successfully target the canine DJ-1 gene using SCNT and Cas9. The DJ-1 gene is a protein in most cells. Protein deficiencies can lead to neurodegenerative diseases such as Parkinson’s and Alzheimer’s. Instead of solving the DJ-1 deficiency, this study actually partially and completely repressed the DJ-1 gene in two dogs.
This study has interesting implications because the methods can be used to either continue repressing the DJ-1 gene in dogs or correct the DJ-1 deficiencies. Either approach could provide valuable insight into the functions DJ-1 plays. While DJ-1 has been edited in rats and mice, this is the first time such methods have been successfully used in dogs. Additionally, this study provides tentative hope that other specific proteins could be targeted using gene editing and therapy.
