Novel Gene Editing Platform to Correct Multi-organ Cystic Fibrosis

An interdisciplinary team of Yale researchers has developed a novel gene editing platform that has the potential to correct cystic fibrosis (CF), a potentially debilitating and deadly disease.

Cystic fibrosis is caused by a mutation in a gene called the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR). It is often thought of as a lung disease because some of the most severe implications occur in the airways, but it can also affect multiple organs in the body, including the pancreas, small and large intestines, and colon.

In a new study, published in Science Advances, researchers from the Department of Pediatrics (Egan Research Group), the Department of Therapeutic Radiology (Glazer Research Group), both at Yale School of Medicine, and the Saltzman Research Group at the Yale School of Engineering & Applied Science, described the intravenous administration of a set of gene editing reagents encapsulated in polymeric nanoparticles. The gene editing approach was tested in CF mice. The researchers discovered that the treatment resulted in a partial gain of CFTR function.

The data suggest that this treatment can ameliorate CF in multiple affected organs, with implications for how the disease may eventually be treated in humans.

“This is the first study looking at treating multiple organs affected by CF with a single gene editing treatment administered intravenously,” said lead author Alexandra Piotrowski-Daspit, PhD, a postdoctoral fellow in the Saltzman, Egan, and Glazer research groups. “The power of gene editing is that you can correct the underlying cause, so that you’re not necessarily looking at lifelong treatments. If you can optimize the delivery to the specific organs, you’re looking at a one-time cure.”

This treatment and technology could potentially address all of the more than 1,700 different mutations that cause CF, as well as any genetic disorder, with wide-ranging implications. Gene-editing is a therapy that can be used at any stage of life.

Other authors on the study include Christina Barone, Chun-Yu Lin, Yanxiang Deng, Douglas Wu, Thomas C. Binns, Emily Xu, Adele S. Ricciardi, Rachael Putman, Alannah Garrison, Richard Nguyen, Anisha Gupta, Rong Fan, Peter M. Glazer, W. Mark Saltzman, and Marie. E. Egan. All of these authors were at Yale at the time of the study.

This study was funded by the National Institutes of Health and the Cystic Fibrosis Foundation.

More information, including a copy of the paper, can be found online at Science Advances.