Cocal-pseudotyped lentiviral vectors resist inactivation by human serum and efficiently transduce primate hematopoietic repopulating cells.
Lentiviral vectors are established as efficient and convenient vehicles for gene transfer. They are almost always pseudotyped with the envelope glycoprotein of vesicular stomatitis virus (VSV-G) due to the high titers that can be achieved, their stability, and broad tropism. We generated a novel cocal vesiculovirus envelope glycoprotein plasmid and compared the properties of lentiviral vectors pseudotyped with cocal, VSV-G, and a modified feline endogenous retrovirus envelope glycoprotein (RD114/TR). Cocal-pseudotyped lentiviral vectors can be produced at titers as high as with VSV-G, have a broad tropism, and are stable, allowing for efficient concentration by centrifugation. Additionally, cocal vectors are more resistant to inactivation by human serum than VSV-G-pseudotyped vectors, and efficiently transduce human CD34(+) nonobese diabetic/severe combined immunodeficient (NOD/SCID) mouse-repopulating cells (SRCs), and long-term primate hematopoietic repopulating cells. These studies establish the potential of cocal-pseudotyped lentiviral vectors for a variety of scientific and therapeutic gene transfer applications, including in vivo gene delivery and hematopoietic stem cell (HSC) gene therapy.
Trobridge
Grant D
GD
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, USA.
Wu
Robert A
RA
Hansen
Michael
M
Ironside
Christina
C
Watts
Korashon L
KL
Olsen
Philip
P
Beard
Brian C
BC
Kiem
Hans-Peter
HP
D000818:Animals; D018952:Antigens, CD34 / Q000235:genetics; D002415:Cats; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics / Q000276:immunology*; D006412:Hematopoietic Stem Cells; D006801:Humans; D016086:Lentivirus / Q000235:genetics / Q000276:immunology*; D008251:Macaca; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D016513:Mice, SCID; D011984:Sensory Receptor Cells; D014161:Transduction, Genetic; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology
D018952:Antigens, CD34; D008562:Membrane Glycoproteins; D014759:Viral Envelope Proteins; C114950:glycoprotein G, Cocal virus