Repairing Mutations in Cystic Fibrosis Using CRISPR-Cas

A new approach adopted by researchers at the University of Trento opens doors for new perspectives in the treatment of cystic fibrosis, a genetic disease for which no cure is currently available. The researchers developed a genome-editing approach, which they applied to intestinal organoids. The results of the study were published today in Nature Communications.

“Instead of animal models, we have used organoids that we developed from the patients’ cells, a choice that allowed us to verify the efficacy of the molecular strategy in a context that is very similar to that of the patients with cystic fibrosis,” says first author Giulia Maule.

Cystic fibrosis is sometimes called the invisible disease because it doesn’t show on the outside, and yet it takes a huge toll on the lives of the people it affects. Most of all, individuals with cystic fibrosis suffer lung and digestive problems. In Italy, there are about 6,000 people who have cystic fibrosis, with an average of 200 new cases being diagnosed each year.

Cystic fibrosis is caused by a mutation of the gene that produces the cystic fibrosis transmembrane conductance regulator (CFTR), whose malfunctioning affects multiple organs—especially the lungs. For their study, the researchers edited at least two variations of the mutation that causes cystic fibrosis using an adapted CRISPR-Cas system. Their specific technique is called “SpliceFix” because it fixes the gene and restores the protein production mechanism at the same time.

“We have devised a genome editing strategy based on CRISPR-Cas to permanently remove two different mutations that cause the disease,” Maule explains. “CRISPR-Cas works like a genomic scalpel to cut out the mutated elements with extreme accuracy. We demonstrated that our repair strategy works on patient-derived organoids and with a high level of precision: it targets only the mutated sequences, leaving non-mutated DNA untouched.”