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In Vivo Gene Transfer Using a Nonprimate Lentiviral Vector Pseudotyped with Ross River Virus Glycoproteins

Publication ,  Journal Article
Kang, Y; Stein, CS; Heth, JA; Sinn, PL; Penisten, AK; Staber, PD; Ratliff, KL; Shen, H; Barker, CK; Martins, I; Sharkey, CM; Sanders, DA ...
Published in: Journal of Virology
September 15, 2002

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 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.

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Published In

Journal of Virology

DOI

EISSN

1098-5514

ISSN

0022-538X

Publication Date

September 15, 2002

Volume

76

Issue

18

Start / End Page

9378 / 9388

Publisher

American Society for Microbiology

Related Subject Headings

  • Virology
  • 32 Biomedical and clinical sciences
  • 31 Biological sciences
  • 30 Agricultural, veterinary and food sciences
  • 11 Medical and Health Sciences
  • 07 Agricultural and Veterinary Sciences
  • 06 Biological Sciences
 

Citation

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Kang, Y., Stein, C. S., Heth, J. A., Sinn, P. L., Penisten, A. K., Staber, P. D., … Davidson, B. L. (2002). In Vivo Gene Transfer Using a Nonprimate Lentiviral Vector Pseudotyped with Ross River Virus Glycoproteins. Journal of Virology, 76(18), 9378–9388. https://doi.org/10.1128/jvi.76.18.9378-9388.2002
Kang, Yubin, Colleen S. Stein, Jason A. Heth, Patrick L. Sinn, Andrea K. Penisten, Patrick D. Staber, Kenneth L. Ratliff, et al. “In Vivo Gene Transfer Using a Nonprimate Lentiviral Vector Pseudotyped with Ross River Virus Glycoproteins.” Journal of Virology 76, no. 18 (September 15, 2002): 9378–88. https://doi.org/10.1128/jvi.76.18.9378-9388.2002.
Kang Y, Stein CS, Heth JA, Sinn PL, Penisten AK, Staber PD, et al. In Vivo Gene Transfer Using a Nonprimate Lentiviral Vector Pseudotyped with Ross River Virus Glycoproteins. Journal of Virology. 2002 Sep 15;76(18):9378–88.
Kang, Yubin, et al. “In Vivo Gene Transfer Using a Nonprimate Lentiviral Vector Pseudotyped with Ross River Virus Glycoproteins.” Journal of Virology, vol. 76, no. 18, American Society for Microbiology, Sept. 2002, pp. 9378–88. Crossref, doi:10.1128/jvi.76.18.9378-9388.2002.
Kang Y, Stein CS, Heth JA, Sinn PL, Penisten AK, Staber PD, Ratliff KL, Shen H, Barker CK, Martins I, Sharkey CM, Sanders DA, McCray PB, Davidson BL. In Vivo Gene Transfer Using a Nonprimate Lentiviral Vector Pseudotyped with Ross River Virus Glycoproteins. Journal of Virology. American Society for Microbiology; 2002 Sep 15;76(18):9378–9388.

Published In

Journal of Virology

DOI

EISSN

1098-5514

ISSN

0022-538X

Publication Date

September 15, 2002

Volume

76

Issue

18

Start / End Page

9378 / 9388

Publisher

American Society for Microbiology

Related Subject Headings

  • Virology
  • 32 Biomedical and clinical sciences
  • 31 Biological sciences
  • 30 Agricultural, veterinary and food sciences
  • 11 Medical and Health Sciences
  • 07 Agricultural and Veterinary Sciences
  • 06 Biological Sciences