Ebola virus glycoproteins: guidance devices for targeting gene therapy vectors

Abstract

Replacing the native viral envelope protein on the surface of a retrovirus or lentivirus with the glycoprotein of a foreign enveloped virus, a process called pseudotyping, can expand the set of potential target cells for a viral vector or can restrict entry to specific cells. The Ebola virus glycoprotein, because of its evolutionary origins and the route of viral entry promoted by it, possesses distinct advantages in forming the outer shell of such pseudotyped retroviruses for gene therapy applications. Studies of the transduction of human airway epithelia by lentivirus pseudotyped with a modified Ebola virus glycoprotein from which the region of O-glycosylation has been removed have demonstrated that such recombinant viruses possess particular promise for the treatment of cystic fibrosis. This result highlights the synergism between basic studies of virus entry and gene therapy advances.