Peptides to deliver gene editing tools to airway cells

Peptides to deliver gene editing tools to airway cells

News of advances in gene-editing technology raises the prospect of actually using this approach to treat disease in patients. But one of the hurdles that remains is how to deliver these tools to the right cells in the patients safely and efficiently.

Scientists are using simple peptides to deliver gene-editing tools into notoriously hard-to-access lung and airway cells with the goal of creating new treatments for people with diseases like cystic fibrosis, COPD, and asthma.

In a new study published in Nature Communications, the team showed that these cell-penetrating, "shuttle" peptides can carry gene-editing proteins into airway cells without causing harm to the cells or the animal model being tested, and achieve gene editing at levels that might be useful clinically.

"There is a lot of excitement about the possibility of using gene editing in medicine to treat diseases by repairing or modifying disease-causing mutations," says the senior author. "But the issue is that we have to be able to safely deliver the materials. This research is one step in that path."

The peptides use sequences borrowed from nature that allow them to rapidly pass through cell membranes and escape cell mechanisms designed to remove foreign DNA or proteins. In the new study, the researchers were able to deliver proteins and gene-editing ribonucleoproteins to human airway cells and mouse lungs. The process resulted in gene editing in the airway cells at a level that was high enough to be potentially useful for therapies, but was well-tolerated and did not persist or produce "off-target" editing.

The senior author says one of the next steps is to screen about 100 new peptides in an effort to identify ones that are even more efficient at delivering biological cargoes.