In vivo gene marking of rhesus macaque long-term repopulating hematopoietic cells using a VSV-G pseudotyped versus amphotropic oncoretroviral vector Journal Article


Authors: Shi, P. A.; De Angioletti, M.; Donahue, R. E.; Notaro, R.; Luzzatto, L.; Dunbar, C. E.
Article Title: In vivo gene marking of rhesus macaque long-term repopulating hematopoietic cells using a VSV-G pseudotyped versus amphotropic oncoretroviral vector
Abstract: Background. Gene transfer efficiency into primitive hematopoietic cells may be limited by their expression of surface receptors allowing vector entry. Vectors pseudotyped with the vesicular stomatitis virus (VSV-G) envelope do not need receptors to enter cells, and therefore may provide superior transduction efficiency. Methods. Using a competitive repopulation model in the rhesus macaque, we examined in vivo gene marking levels of blood cells transduced with two vectors: (i) a VSV-G pseudotyped retrovirus and (ii) a conventional amphotropic retrovirus. The VSV-G vector, containing the human glucose-6-phosphate dehydrogenase (G6PD) gene, was constructed for treatment of severe hemolytic anemia caused by G6PD deficiency. Three myeloablated animals were transplanted with peripheral blood CD34+ cells, half of which were transduced with the VSV-G vector and the other half with the amphotropic vector. Results. In all animals post-transplantation, levels of in vivo marking in circulating granulocytes and mononuclear cells were similar: 1% or less with both vectors. In one animal, the human G6PD enzyme transferred by the VSV-G vector was expressed in erythrocytes, early after transplantation, at a level of 45% of the endogenous rhesus G6PD protein. Conclusions. In a clinically relevant animal model, we found similar in vivo marking with a VSV-G pseudotyped and a standard amphotropic oncoretroviral vector. Amphotropic receptor expression may not be a limiting factor in transduction efficiency, but VSV-G pseudotypes possess other practical advantages that may make them advantageous for clinical use. Copyright © 2004 John Wiley & Sons, Ltd.
Keywords: controlled study; protein expression; nonhuman; animal cell; animals; cells, cultured; cd34 antigen; animal experiment; animal model; hematopoietic stem cell transplantation; in vivo study; gene transfer; viral gene delivery system; animalia; genetic vectors; transduction, genetic; disease severity; mononuclear cell; retrovirus vector; hematopoietic cell; hemolytic anemia; hematopoietic stem cells; cell count; genes, reporter; macaca mulatta; population dynamics; antigens, cd34; granulocyte; genetic markers; retroviridae; gene transfer techniques; rhesus monkey; vesicular stomatitis virus; glucose 6 phosphate dehydrogenase; glucosephosphate dehydrogenase; unidentified retrovirus; humans; priority journal; article; glucose-6-phosphate dehydrogenase deficiency; vsv-g protein; vesicular stomatitis-indiana virus
Journal Title: Journal of Gene Medicine
Volume: 6
Issue: 4
ISSN: 1099-498X
Publisher: John Wiley & Sons  
Date Published: 2004-04-01
Start Page: 367
End Page: 373
Language: English
DOI: 10.1002/jgm.514
PROVIDER: scopus
PUBMED: 15079811
DOI/URL:
Notes: J. Gene Med. -- Cited By (since 1996):8 -- Export Date: 16 June 2014 -- CODEN: JGMEF -- Source: Scopus
Altmetric Score
MSK Authors
  1. Lucio Luzzatto
    104 Luzzatto