Therapeutical studies of the disrupted CFTR gene in affected sheep and rabbit models produced by genome editor CRISPR/Cas9

Cystic Fibrosis (CF) is a life-threatening, autosomal recessive disorder caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. Patients with CF have a decreased lifespan due to complications with lung infections/disease, decreased airway function, and persistent cough with phlegm. Over the past few decades, scientists have contributed to CF research by using animal models to understand the pathology of the disease. The models selected have similar pathogenesis to humans, so they are key insights for understanding the effects of CFTR gene malfunctions. More recently, animal models, such as CRISPR generated sheep and rabbits used in the two current studies, have been successful in providing scientists with insights for promising therapeutical advances that could be used in humans with CF. In the first study, sheep have been generated using CRISPR technology and somatic cell nuclear transfer techniques. The models used for the study had a disruption in the CFTR gene to produce CFTR heterozygous and homozygous offspring. Newborn homozygous sheep developed phenotypes consistent with CF pathology seen in humans. The second study used the same CRISPR technology technique to generate CF rabbits with a disrupted CFTR gene. CF rabbits receiving an oral osmotic laxative survived an average of 40 days and 100% died due to gastrointestinal disease. The rabbits also mimicked phenotypes shown in humans with CF such as decreased respiratory function and gastrointestinal obstruction. Here, we explain how the use of sheep and rabbit models help to test the effects of a mutated CFTR gene and provide further therapeutical advances that could be helpful for individuals living with Cystic Fibrosis. These two models have been successful in understanding CF pathology and suggest that there is hope for finding a cure for Cystic Fibrosis is the near future