THE ROLE OF CRISPR/Cas9 IN THE STUDY OF GENETIC DISEASE: CYSTIC FIBROSIS

Abstract

Cystic Fibrosis (CF) is considered the most common lethal genetic disease in Caucasian populations, which is characterized by chronic and recurrent infections of the lung, pancreatic insufficiency and high levels of chlorine in sweat. This autosomal recessive inheritance disease is caused by the mutation in the Cystic Fibrosis Transmembrane Conductance Regulator gene, which induces the body to produce thick, viscous secretions that obstruct the lungs, pancreas and bile duct. Many patients manifest pancreatic insufficiency, the consequences of which are: malabsorption of nutrients, especially proteins and lipids, as well as gastrointestinal complications. CF is usually diagnosed during childhood, through neonatal screening programs, sweat testing and genetic analysis. Due to the various systems involved and the variability and chronicity of the disease, a multidisciplinary approach is essential to assist the patient and his family. Current CF therapy includes maintaining nutritional status, using antibiotics to prevent and treat infections, removing airway secretions with physiotherapy and mucolytics, indicating energy supplements and diets, although the treatment is only palliative. Gene therapy is a treatment based on the transfer of copies of genetic material without mutation to the organism of interest, enabling the correction of the phenotype of disorders caused by genetic mutations. With technological advances and discoveries, regarding the function of genes and genetic material, several methodologies capable of correcting the human genome have been developed. The CRISPR / Cas9 system (clustered regularly short palindromic repeats-CRISPR associated nucleases) has stood out due to its versatility, ability to perform the desired change and simplicity of handling in the laboratory. In view of the above, CF has been the target of studies with the use of gene therapy.