CRISPR Corrects Cystic Fibrosis Mutation and Rescues CFTR Function

Cystic Fibrosis (CF) is a genetic disease caused by a mutation in the CFTR gene (cystic fibrosis transmembrane conductance regulator protein). This gene encodes a chloride ion membrane channel which is used to make mucus, sweat and other fluids required for digestion. The most common mutation of the CFTR gene is the ΔF508 mutation, it approximately occurs in more than 70% of CF patients.

Individuals that have a CFTR mutation, either do not produce CFTR at all or produce a dysfunctional CFTR, whereby it is shortened or misfolded, which greatly affects the CFTR channel function. The chloride ions are unable to pass through the CFTR channel, which causes damage to the lungs, sweat ducts, and pancreas. In the lungs, there's a build-up of sticky thick mucus due to the blocked CFTR channel.

Whilst there are no cures available for CF, there are some treatment options. Many CF patients are susceptible to chronic airway infections, therefore CF patients rely on regular antibiotic usage. Furthermore, medicines that loosen thick mucus are used, and there are also CFTR modulator therapies that are used to correct the dysfunctional CFTR shape making it more likely that the channel is open, but even with these treatments, in severe cases, patients may still require lung transplantation. Therefore alternative treatment options must be researched.

A study was conducted at Stanford University and was published in Cell Stem Cell.

Scientists used CRISPR-Cas9 to repair the ΔF508 mutation in airway stem cells belonging to CF patients. It was found that there was correction in more than 30% of the mutated alleles and the CRISPR edited cells had CFTR expression. Whereas, the unedited CF cells had no mature CFTR expression and only had expression of immature CFTR. Therefore, the CRISPR edited cells were capable of producing the CFTR protein.

Then the scientists wanted to determine the CFTR function of the CRISPR edited cells, it was found that 20-50% CFTR function was restored compared to the normal functioning CFTR controls. After the CFTR function was verified, the cells containing corrected CFTR were placed on a scaffold and it was found that these corrected cells were able to differentiate.

This research shows promising results for the use of CRISPR in cells. If this research translates well in future human studies, it could one day be a life-changing CF treatment.