1. ¹Division of Medical Genetics, Philadelphia, Pennsylvania 19104, USA
2. ²The Wistar Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
3. ³Department of Microbiology, Philadelphia, Pennsylvania 19104, USA
4. ⁴Department of Medicine, University of California at San Diego, La Jolla, California 92093, USA

Correspondence: James M. Wilson, 204 Wistar, 3601 Spruce Street, Philadelphia, PA 19104, USA. Fax: (215) 898-6588. E-mail: wilsonjm@mail.med.upenn.edu

Received 25 June 2003; Accepted 14 July 2003.

Abstract

A human immunodeficiency virus (HIV)-based vector pseudotyped with the Ebola Zaire (EboZ) viral envelope glycoprotein (GP) was recently shown to transduce murine airway epithelia cells in vivo. In this study, the vector was further redesigned to improve gene transfer and also to increase safety. We used mutant EboZ envelopes for pseudotyping, which resulted in higher titers and increased transduction of airway cells in vivo compared to vectors pseudotyped with wild-type EboZ GP. As these envelopes lack regions associated with toxicity of the wild-type EboZ GP, they should also be safer to use for pseudotyping of lentiviral vectors. In addition, lentiviral vectors were created based on feline immunodeficiency virus and shown to have similar efficiency of transduction compared to HIV-based vectors. The creation of lentiviral vectors with highly engineered EboZ envelopes improved the performance of the system and should also increase its safety since only minimal regions of the EboZ envelope, which lack the toxic domain, are used.