Lentiviral vectors pseudotyped with baculovirus gp64 efficiently transduce mouse cells in vivo and show tropism restriction against hematopoietic cell types in vitro.
The envelope glycoprotein from vesicular stomatitis virus (VSV-G) has been used extensively to pseudotype lentiviral vectors, but has several drawbacks including cytotoxicity, potential for priming of immune responses against transgene products through efficient transduction of antigen-presenting cells (APCs) and sensitivity to inactivation by human complement. As an alternative to VSV-G, we extensively characterized lentiviral vectors pseudotyped with the gp64 envelope glycoprotein from baculovirus both in vitro and in vivo. We demonstrated for the first time that gp64-pseudotyped vectors could be delivered efficiently in vivo in mice via portal vein injection. Following delivery, the efficiency of mouse cell transduction and the transgene expression is comparable to VSV-G-pseudotyped vectors. In addition, we found that gp64-pseudotyped lentiviral vectors could efficiently transduce a variety of cell lines in vitro, although gp64 showed a more restricted tropism than VSV-G, with especially poor ability to transduce hematopoietic cell types including dendritic cells (DCs). Although we found that gp64-pseudotyped vectors are also sensitive to inactivation by human complement, gp64 nevertheless has advantages over VSV-G, because of its lack of cytotoxicity and narrower tropism. Consequently, gp64 is an attractive alternative to VSV-G because it can efficiently transduce cells in vivo and may reduce immune responses against the transgene product or viral vector by avoiding transduction of APCs such as DCs.
Schauber
C A
CA
Cell Genesys Inc., South San Francisco, CA 94080, USA.
Tuerk
M J
MJ
Pacheco
C D
CD
Escarpe
P A
PA
Veres
G
G
D000818:Animals; D016367:Baculoviridae / Q000235:genetics; D002460:Cell Line; D003165:Complement System Proteins / Q000276:immunology; D003713:Dendritic Cells / Q000378:metabolism / Q000821:virology; D005164:Factor IX / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D005822:Genetic Vectors; D015497:HIV-1 / Q000235:genetics; D006413:Hematopoietic System / Q000378:metabolism / Q000821:virology; D006801:Humans; D016086:Lentivirus / Q000235:genetics* / Q000472:pathogenicity; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D051381:Rats; D014161:Transduction, Genetic / Q000379:methods*; D018523:Tropism; D014760:Viral Fusion Proteins / Q000235:genetics*
D014760:Viral Fusion Proteins; D005164:Factor IX; D003165:Complement System Proteins