New Strategy Could Correct Genetic Mutation Responsible For Cystic Fibrosis

Researchers at Yale University and Yale School of Medicine in Connecticut recently published in the journal Nature Communications that they were able to successfully correct the most common mutation in the gene responsible for cystic fibrosis (CF). The study is entitled “Nanoparticles that deliver triplex-forming peptide nucleic acid molecules correct F508del CFTR in airway epithelium.”

CF is a life-threatening genetic disease in which a defective gene, called cystic fibrosis transmembrane conductance regulator (CFTR), causes the body to form unusually thick, sticky mucus that can result in serious respiratory and gastrointestinal manifestations. There is no cure for CF and the therapies available aim at the management of disease symptoms. CF is, in the majority of cases, caused by a specific CFTR mutation – F508del. Previous treatment attempts based on gene therapy have, however, failed.

A collaborative team of Yale researchers were able to correct the F508del mutation in the CFTR gene with a new approach that utilizes donor DNA and synthetic triplex-forming molecules similar to DNA, known as peptide nucleic acids (PNAs). “What the PNA does is clamp to the DNA close to the mutation, triggering DNA repair and recombination pathways in cells,” explained the study’s senior author Dr. Marie Egan in a news release.

The research team also developed a new delivery approach of the PNA/DNA through intranasal delivery of biodegradable microscopic nanoparticles, which have been specifically designed to penetrate in the target cells.

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By using this technique, researchers found that the repair mechanism was efficient in both human airway cells and mouse nasal cells. “The percentage of cells in humans and in mice that we were able to edit was higher than has been previously reported in gene editing technology,” noted Dr. Egan. Researchers also found that this therapeutic strategy based on gene editing had minimal unintended or off target effects on the treated cells.

“This is step one in a long process. The technology could be used as a way to fix the basic genetic defect in cystic fibrosis,” concluded Dr. Egan. The research team suggests that further studies should be conducted to improve this promising genetic engineering strategy.