Cocal-pseudotyped lentiviral vectors resist inactivation by human serum and efficiently transduce primate hematopoietic repopulating cells.

Publication Type:

Journal Article

Source:

Molecular therapy : the journal of the American Society of Gene Therapy, Volume 18, Issue 4, p.725-33 (2010)

Keywords:

2010, Animals, Antigens, CD34, Cats, Center-Authored Paper, Clinical Research Division, Gene Therapy, Genetic Vectors, Hematopoietic Stem Cells, Humans, Lentivirus, Macaca, Membrane Glycoproteins, MICE, Mice, SCID, Sensory Receptor Cells, Transduction, Genetic, Viral Envelope Proteins

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.