Editing away a genetic disorder

The genetic disease cystic fibrosis is caused by a mutation in the cystic fibrosis gene CFTR, normally involved in the production of digestive fluids and mucus. Patients can have difficulty breathing, frequent lung infections, and other complications, and while symptoms can be managed, the disorder has no known cure.

New research reported April 27 in Nature Communications by Yale scientists suggests that inhaling a nasal spray containing tiny nanoparticles, specially engineered to carry genetic information, might be the next big treatment for cystic fibrosis.

The team, led by Marie E. Egan, M.D., professor of pediatrics and of cellular and molecular physiology, Peter M. Glazer, M.D., Ph.D., chair and professor of therapeutic radiology, and W. Mark Saltzman, Ph.D., the Goizueta Foundation Professor of Biomedical Engineering, designed bits of DNA that cause cells to turn on their gene-editing program and repair the CFTR mutation. When they implanted these molecules inside nanoparticles and applied the nanoparticles to the noses of mice, close to 10 percent of the animals’ airway cells became mutation-free—enough to change airway function.

“The technology could be used as a way to fix the basic genetic defect in cystic fibrosis,” Egan said.