Lentiviral vectors pseudotyped with minimal filovirus envelopes increased gene transfer in murine lung.
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.
Medina
Maria Fe
MF
Division of Medical Genetics, Philadelphia, Pennsylvania 19104, USA.
Kobinger
Gary P
GP
Rux
John
J
Gasmi
Mehdi
M
Looney
David J
DJ
Bates
Paul
P
Wilson
James M
JM
D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D003550:Cystic Fibrosis / Q000235:genetics; D029043:Ebolavirus / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel; D016563:Filoviridae / Q000235:genetics*; D017353:Gene Deletion; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006678:HIV / Q000235:genetics; D006801:Humans; D016086:Lentivirus / Q000235:genetics*; D008168:Lung / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009154:Mutation; D010957:Plasmids / Q000378:metabolism; D017434:Protein Structure, Tertiary; D014162:Transfection; D014759:Viral Envelope Proteins / Q000235:genetics*
D014759:Viral Envelope Proteins