title: Cocal-pseudotyped lentiviral vectors resist inactivation by human serum and efficiently transduce primate hematopoietic repopulating cells.
abstract: 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.
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, USA.
authors.forename: Grant D
authors.initials: GD
authors.lastname: Trobridge
authors.forename: Robert A
authors.initials: RA
authors.lastname: Wu
authors.forename: Michael
authors.initials: M
authors.lastname: Hansen
authors.forename: Christina
authors.initials: C
authors.lastname: Ironside
authors.forename: Korashon L
authors.initials: KL
authors.lastname: Watts
authors.forename: Philip
authors.initials: P
authors.lastname: Olsen
authors.forename: Brian C
authors.initials: BC
authors.lastname: Beard
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Kiem
mesh_terms: 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
chemical_list: D018952:Antigens, CD34; D008562:Membrane Glycoproteins; D014759:Viral Envelope Proteins; C114950:glycoprotein G, Cocal virus