Intra-articular delivery of a herpes simplex virus IL-1Ra gene vector reduces inflammation in a rabbit model of arthritis

T. Oligino, S. C. Ghivizzani, D. Wolfe, E. R. Lechman, D. Krisky, Z. Mi, Christopher H Evans, P. D. Robbins, J. C. Glorioso

Research output: Contribution to journalArticle

96 Citations (Scopus)

Abstract

To evaluate the use of HSV-based vectors for arthritis gene therapy we have constructed a first-generation, ICP4 deficient, replication defective herpes simplex virus (HSV) vector (S/O-) and a second-generation HSV vector derivative (T/O-) deficient for the immediate-early genes ICP4, 22 and 27, each carrying a soluble TNF receptor or IL-1 receptor antagonist transgene cassette. A rabbit synovial-fibroblast line in culture, infected by either vector enabled high-level expression of the transgene product. However, following a single intra-articular injection of the vectors into rabbit knee joints, only the second-generation, HSV T/O- vector expressed detectable levels of soluble TNFR in synovial fluid. Synovial lavage fluid from inoculated joints contained up to 12 ng/ml of soluble receptor that persisted at detectable, but reduced levels for at least 7 days. When tested in an experimental model of arthritis generated by intra-articular overexpression of interleukin-1β using retrovirus transduced synovial cells, the HSV T/O- vector expressing the interleukin-1 receptor antagonist was found to inhibit leukocytosis and synovitis significantly. The improved levels and duration of intra-articular transgene expression achieved via HSV-mediated gene delivery suggest that an HSV vector system could be used for therapeutic applications in patients with rheumatoid arthritis (RA) and other joint-related inflammatory diseases.

Original languageEnglish (US)
Pages (from-to)1713-1720
Number of pages8
JournalGene Therapy
Volume6
Issue number10
DOIs
StatePublished - Oct 1999
Externally publishedYes

Fingerprint

Interleukin 1 Receptor Antagonist Protein
Simplexvirus
Arthritis
Joints
Rabbits
Inflammation
Genes
Transgenes
Interleukin-1 Receptors
Synovial Fluid
Defective Viruses
Intra-Articular Injections
Immediate-Early Genes
Experimental Arthritis
Synovitis
Tumor Necrosis Factor Receptors
Therapeutic Irrigation
Leukocytosis
Retroviridae
Knee Joint

Keywords

  • Arthritis
  • HSV
  • IL-1Ra
  • sTNFR

ASJC Scopus subject areas

  • Genetics

Cite this

Oligino, T., Ghivizzani, S. C., Wolfe, D., Lechman, E. R., Krisky, D., Mi, Z., ... Glorioso, J. C. (1999). Intra-articular delivery of a herpes simplex virus IL-1Ra gene vector reduces inflammation in a rabbit model of arthritis. Gene Therapy, 6(10), 1713-1720. https://doi.org/10.1038/sj.gt.3301014

Intra-articular delivery of a herpes simplex virus IL-1Ra gene vector reduces inflammation in a rabbit model of arthritis. / Oligino, T.; Ghivizzani, S. C.; Wolfe, D.; Lechman, E. R.; Krisky, D.; Mi, Z.; Evans, Christopher H; Robbins, P. D.; Glorioso, J. C.

In: Gene Therapy, Vol. 6, No. 10, 10.1999, p. 1713-1720.

Research output: Contribution to journalArticle

Oligino, T, Ghivizzani, SC, Wolfe, D, Lechman, ER, Krisky, D, Mi, Z, Evans, CH, Robbins, PD & Glorioso, JC 1999, 'Intra-articular delivery of a herpes simplex virus IL-1Ra gene vector reduces inflammation in a rabbit model of arthritis', Gene Therapy, vol. 6, no. 10, pp. 1713-1720. https://doi.org/10.1038/sj.gt.3301014
Oligino, T. ; Ghivizzani, S. C. ; Wolfe, D. ; Lechman, E. R. ; Krisky, D. ; Mi, Z. ; Evans, Christopher H ; Robbins, P. D. ; Glorioso, J. C. / Intra-articular delivery of a herpes simplex virus IL-1Ra gene vector reduces inflammation in a rabbit model of arthritis. In: Gene Therapy. 1999 ; Vol. 6, No. 10. pp. 1713-1720.
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