Direct retrovirus-mediated gene transfer to the synovium of the rabbit knee: Implications for arthritis gene therapy

S. C. Ghivizzani, E. R. Lechman, C. Tio, K. M. Mule, S. Chada, J. E. McCormack, C. H. Evans, P. D. Robbins

Research output: Contribution to journalArticlepeer-review

91 Scopus citations

Abstract

We have investigated the feasibility of using high-titer murine leukemia virus-based retroviral vectors to deliver exogenous genes to naive and chronically inflamed knee joints of rabbits in vivo. Intraarticular injection of retrovirus encoding β-galactosidase (β-gal or lacZ) was found to transduce synoviocytes in both naive and inflamed joints, but a significantly higher number of lacZ+ cells were found in inflamed knees. Using a retrovirus encoding a secretable marker, human growth hormone (hGH), quantitative comparison of ex vivo gene delivery methods demonstrated that transgene expression following in vivo gene transfer was at least equivalent to that of the ex vivo method in inflamed knees. In addition, hGH transgene expression was maintained for at least 4 weeks. These experiments suggest that high-titer retroviral vector could be used for efficient in vivo gene transfer to inflamed joints in patients with rheumatoid arthritis (RA).

Original languageEnglish (US)
Pages (from-to)977-982
Number of pages6
JournalGene therapy
Volume4
Issue number9
DOIs
StatePublished - 1997
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported in part by a fellowship to SCG from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, Public Health Service Grant DK44935, and a grant from the Western Pennsylvania Chapter of the Arthritis Foundation.

Keywords

  • In vivo gene delivery
  • Retroviral vectors
  • Rheumatoid arthritis
  • Synovium

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