Journal article
In Vivo Gene Transfer Using a Nonprimate Lentiviral Vector Pseudotyped with Ross River Virus Glycoproteins
Journal of virology, Vol.76(18), pp.9378-9388
09/2002
DOI: 10.1128/JVI.76.18.9378-9388.2002
PMCID: PMC136422
PMID: 12186920
Abstract
Vectors derived from lentiviruses provide a promising gene delivery system. We examined the in vivo gene transfer efficiency and tissue or cell tropism of a feline immunodeficiency virus (FIV)-based lentiviral vector pseudotyped with the glycoproteins from Ross River Virus (RRV). RRV glycoproteins were efficiently incorporated into FIV virions, generating preparations of FIV vector, which after concentration attain titers up to 1.5 × 10
8
TU/ml. After systemic administration, RRV-pseudotyped FIV vectors (RRV/FIV) predominantly transduced the liver of recipient mice. Transduction efficiency in the liver with the RRV/FIV was ca. 20-fold higher than that achieved with the vesicular stomatitis virus G protein (VSV-G) pseudotype. Moreover, in comparison to VSV-G, the RRV glycoproteins caused less cytotoxicity, as determined from the levels of glutamic pyruvic transaminase and glutamic oxalacetic transaminase in serum. Although hepatocytes were the main liver cell type transduced, nonhepatocytes (mainly Kupffer cells) were also transduced. The percentages of the transduced nonhepatocytes were comparable between RRV and VSV-G pseudotypes and did not correlate with the production of antibody against the transgene product. After injection into brain, RRV/FIV preferentially transduced neuroglial cells (astrocytes and oligodendrocytes). In contrast to the VSV-G protein that targets predominantly neurons, <10% of the brain cells transduced with the RRV pseudotyped vector were neurons. Finally, the gene transfer efficiencies of RRV/FIV after direct application to skeletal muscle or airway were also examined and, although transgene-expressing cells were detected, their proportions were low. Our data support the utility of RRV glycoprotein-pseudotyped FIV lentiviral vectors for hepatocyte- and neuroglia-related disease applications.
Details
- Title: Subtitle
- In Vivo Gene Transfer Using a Nonprimate Lentiviral Vector Pseudotyped with Ross River Virus Glycoproteins
- Creators
- Yubin Kang - Program in Gene Therapy, Department of PediatricsColleen S Stein - Program in Gene Therapy, Department of PediatricsJason A Heth - Program in Gene Therapy, Department of PediatricsPatrick L Sinn - Program in Gene Therapy, Department of PediatricsAndrea K Penisten - Program in Gene Therapy, Department of PediatricsPatrick D Staber - Program in Gene Therapy, Department of PediatricsKenneth L Ratliff - Program in Gene Therapy, Department of PediatricsHong Shen - Program in Gene Therapy, Department of PediatricsCarrie K Barker - Program in Gene Therapy, Department of PediatricsInês Martins - Program in Gene Therapy, Department of PediatricsC. Matthew Sharkey - Program in Gene Therapy, Department of PediatricsDavid Avram Sanders - Program in Gene Therapy, Department of PediatricsPaul B McCray - Program in Gene Therapy, Department of PediatricsBeverly L Davidson - Program in Gene Therapy, Department of Pediatrics
- Resource Type
- Journal article
- Publication Details
- Journal of virology, Vol.76(18), pp.9378-9388
- Publisher
- American Society for Microbiology
- DOI
- 10.1128/JVI.76.18.9378-9388.2002
- PMID
- 12186920
- PMCID
- PMC136422
- ISSN
- 0022-538X
- eISSN
- 1098-5514
- Language
- English
- Date published
- 09/2002
- Academic Unit
- Microbiology and Immunology; Pulmonary Medicine; Stead Family Department of Pediatrics; Internal Medicine
- Record Identifier
- 9984093604302771
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