Genome editing in vascular endothelial cells made possible with a powerful new delivery system

Northwestern Medicine scientists developed a unique nanoparticle to deliver genome editing technology, including CRISPR/Cas9, to endothelial cells, which line blood vessel walls.

Published in Cell Reports, this is the first time that vascular endothelial cells could be reached for genome editing, since the usual way to deliver CRISPR/Cas9 - through a virus - does not work for this cell type, according to YouYang Zhao, PhD, professor of Pediatrics in the Division of Critical Care and senior author of the study.

The nanoparticle we developed is a powerful new delivery system for genome editing in vascular endothelial cells, and could be used to treat many diseases, including acute respiratory distress syndrome from severe COVID-19. With this nanoparticle we can introduce genes to inhibit vascular injury or promote vascular repair, correct gene mutations and turn genes on or off to restore normal function. It also allows us to edit multiple genes at the same time. This is an important advance for treating any disease caused by endothelial dysfunction."

YouYang Zhao, PhD, member of the Stanley Manne Children's Research Institute at Ann & Robert H. Lurie Children's Hospital of Chicago

Endothelial dysfunction is at the root of many diseases, such as coronary artery disease, stroke, bronchopulmonary dysplasia and pulmonary artery hypertension. Zhao explained that genome editing in endothelial cells could even treat cancers by cutting off the blood supply to the tumor or blocking cancer metastasis.

At this stage, Dr. Zhao and colleagues achieved excellent results in a mouse model. The nanoparticle carrying CRISPR/Cas9 plasmid DNA was introduced via a one-time IV injection and required a few days to be effective. Preclinical testing will be necessary before clinical trials can begin.

"Our nanoparticle delivery system for genome editing and transgene expression also is a huge advance for cardiovascular research," Zhao added.