Current studentsExisting staffContact us
 

G-CSF-lentivirus administration in rats provided sustained elevated neutrophil counts and subsequent EPO-lentivirus administration increased hematocrits

Simple item page
dc.contributor.authorBrzezinski, M.
dc.contributor.authorYanay, O.
dc.contributor.authorWaldron, L.
dc.contributor.authorBarry, S.
dc.contributor.authorOsborne, W.
dc.date.issued2007
dc.description.abstract<h4>Background</h4>Towards gene therapy treatment of patients with neutropenia, characterized by neutrophil counts < 500 cells/microl, we investigated the ability of lentivirus vectors to provide sustained granulocyte colony-stimulating factor (G-CSF) delivery and to permit transgene expression from a second virus administration in a preclinical rat model.<h4>Methods</h4>Rats were injected intramuscularly (IM) with 24 x 10(6) and 9 x 10(6) infectious units (IU) of a VSV-G-pseudotyped self-inactivating (SIN) lentivirus encoding rat G-CSF cDNA and containing cPPT and PRE elements. To determine the effectiveness of a second virus administration treated rats and a naïve rat received erythropoietin (EPO)-lentivirus IM. Rats were monitored for neutrophil and red blood cell production. Lentivirus antibodies were assayed by virus-neutralizing assay and ELISA.<h4>Results</h4>High and low dose virus administration increased neutrophil counts to 5660 +/- 930 cells/microl (mean +/- SD) and 4010 +/- 850 cells/microl, respectively, that were sustained for > 17 months and were significantly higher than controls counts of 1890 +/- 570 cells/microl (p< or =0.0002). Rats treated with EPO-virus produced significantly increased hematocrits (HCT) (63.1 +/- 4.3% vs. 46.0 +/- 3.2%, p < 0.0001) without effect on G-CSF-virus-mediated neutrophil production. Antivirus antibodies were not detectable at serum dilutions > or =1:10 by virus neutralization or ELISA. Lymphocytes and platelets were not significantly different between control and treated animals (p > 0.1). Only genomic DNA from muscle at injection sites was positive for provirus suggesting lack of virus spread.<h4>Conclusions</h4>G-CSF-lentivirus administered IM provided elevated, sustained neutrophil counts that were unchanged by subsequent EPO-lentivirus administration. Significantly increased hematocrits were obtained following EPO-lentivirus delivery. These data support the treatment of patients with severe chronic neutropenia by dosed lentivirus delivery IM.
dc.description.statementofresponsibilityMargaret Brzezinski, Ofer Yanay, Lanaya Waldron, Simon C. Barry, William R. A. Osborne
dc.identifier.citationJournal of Gene Medicine, 2007; 9(7):571-578
dc.identifier.doi10.1002/jgm.1050
dc.identifier.issn1099-498X
dc.identifier.issn1521-2254
dc.identifier.orcidBarry, S. [0000-0002-0597-7609]
dc.identifier.urihttp://hdl.handle.net/2440/41981
dc.language.isoen
dc.publisherJohn Wiley & Sons Ltd
dc.source.urihttps://doi.org/10.1002/jgm.1050
dc.subjectNeutrophils
dc.subjectHela Cells
dc.subjectAnimals
dc.subjectRats, Inbred F344
dc.subjectHumans
dc.subjectRats
dc.subjectProviruses
dc.subjectLentivirus
dc.subjectErythropoietin
dc.subjectGranulocyte Colony-Stimulating Factor
dc.subjectDNA
dc.subjectAntibodies, Viral
dc.subjectBlood Cell Count
dc.subjectHematocrit
dc.subjectGenome
dc.subjectMale
dc.subjectGenetic Therapy
dc.titleG-CSF-lentivirus administration in rats provided sustained elevated neutrophil counts and subsequent EPO-lentivirus administration increased hematocrits
dc.typeJournal article
pubs.publication-statusPublished

Files

Collections

Paediatrics publications