Researchers fix cystic fibrosis mutation

Chuck Bednar for redOrbit.com – @BednarChuck

Researchers from Yale have successfully fixed the genetic mutation most frequently responsible for causing cystic fibrosis, a condition that primarily affects the lungs and can result in long-term breathing difficulties, frequent respiratory infections and other symptoms.

The study, published Monday in the journal Nature Communications, explains how the authors were able to correct a mutation in the cystic fibrosis gene known as F508del by using synthetic molecules similar to DNA called peptide nucleic acids (PNAs) as well as donor DNA to edit the genetic defect responsible for the inherited, incurable, life-threatening ailment.

Cystic fibrosis is typically treated through management of symptoms, and previous attempts to address the condition through gene therapy were unsuccessful. In their new approach, however, Dr. Peter Glazer, chair of therapeutic radiology, and his colleagues developed a novel approach that uses PNA to clamp the DNA close to the mutation, causing it to begin repairing itself.

Dr. Glazer, Yale biomedical engineering chair Dr. Mark Saltzman, professor Dr. Marie Egan and their fellow scientists also developed a method that delivers the PNA/DNA combination by using microscopic nanoparticles specifically designed to penetrate targeted cells in patients.

Step one in the search for a cure

“Dr. Glazer is an expert and pioneer in DNA repair and the PNA/DNA Technology. He has developed very unique and sophisticated PNA molecules that are more efficient than previous attempts,” Dr. Egan told redOrbit via email. “Dr. Saltzman has developed newer nanoparticles that are much more efficient at delivering the PNA/DNA. Together this approach has resulted in a higher percentage of cells with the corrected sequence and much lower off target effects.”

They observed corrections in the targeted genes in both human airway cells and in mouse nasal cells, and Dr. Egan explained that they were able to edit a higher percentage of cells in humans and mice than had previously been reported in gene editing technology. She also noted that their new approach had minimal unintended side-effects on the targeted cells.

While the researchers called their findings “significant,” Dr. Egan emphasized that there is far more research that needs to be done in order to refine their genetic engineering approach. She called it the first step in a long process, but added that it was a process which may one day lead to a way to fix the genetic defects responsible for causing cystic fibrosis.

“Changing things in a layer of human airway cells or in a mouse model of cystic fibrosis is a long way from a treatment for people,” she told redOrbit, adding that there are still “many steps” which still need to be done before it can be a full-blown fix for the inherited genetic disorder.

“To name a few: We would need to optimize the particles, optimize the treatment protocol to get the most correction,” the Yale professor added. “We would need to show this is safe over long periods of time in mice and then in larger animals, then would need to show this is safe in people and that it would work in people.”

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