In vivo gene delivery to synovium by lentiviral vectors

Elvire Gouze, Robert Pawliuk, Carmencita Pilapil, Jean Noel Gouze, Christina Fleet, Glyn D. Palmer, Christopher H Evans, Philippe Leboulch, Steven C. Ghivizzani

Research output: Contribution to journalArticle

94 Scopus citations

Abstract

The delivery of anti-arthritic genes to the synovial lining of joints is being explored as a strategy for the treatment of rheumatoid arthritis. In this study, we have investigated the use of VSV-G pseudotyped, HIV-1-based lentiviral vectors for gene delivery to articular tissues. Recombinant lentivirus containing a β-galactosidase/neomycin resistance fusion gene under control of the elongation factor (EF) 1α promoter efficiently transduced human and rat synoviocytes and chondrocytes in cell culture. When directly injected into the knees of rats, this vector transduced synovial lining cells, but not other articular tissues such as cartilage. We also constructed a lentiviral vector containing the human interleukin-1 receptor antagonist (IL1RA) cDNA and examined transgene expression in vitro and in vivo following injection into the knee joints of rats. In immunocompetent animals, intra-articular IL1RA expression was high and persisted, at a sharply declining rate, for approximately 20 days. In immunocompromised rats, however, lentivirus-mediated intra-articular expression of human IL1RA was found to persist for at least 6 weeks. Extra-articular expression of the transgene was minimal. These results indicate that lentiviral vectors are capable of efficient in vivo gene transfer to synovium and merit further investigation as a means of providing long-term expression for gene-based treatments of arthritis.

Original languageEnglish (US)
Pages (from-to)397-404
Number of pages8
JournalMolecular Therapy
Volume5
Issue number4
DOIs
StatePublished - 2002
Externally publishedYes

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Keywords

  • Arthritis
  • Gene therapy
  • IL1RA
  • Lentivirus

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Gouze, E., Pawliuk, R., Pilapil, C., Gouze, J. N., Fleet, C., Palmer, G. D., Evans, C. H., Leboulch, P., & Ghivizzani, S. C. (2002). In vivo gene delivery to synovium by lentiviral vectors. Molecular Therapy, 5(4), 397-404. https://doi.org/10.1006/mthe.2002.0562