Disease-inducible transgene expression from a recombinant adeno- associated virus vector in a rat arthritis model

Ru Yu Pan, Xiao Xiao, Show Li Chen, Juan Li, Leou Chyr Lin, Hsian-Jenn Wang, Yeou Ping Tsao

Research output: Contribution to journalArticle

95 Citations (Scopus)

Abstract

Rheumatoid arthritis (RA) is a systemic autoimmune disease affecting 1% of the world's population, with significant morbidity and mortality. In this study, we investigated a recombinant adeno-associated virus (rAAV) vector for its potential application in RA gene therapy. rAAV encoding Escherichia coli β-galactosidase was injected into rat joints which had already been induced into acute arthritis after local lipopolysaccharides (LPS) administration, and the efficiency of in vivo transduction was evaluated. We observed a striking correlation between vector transgene expression and disease severity in arthritic joints. The inflammatory reaction peaked at 3 to 7 days after LPS treatment, and, at the same time, 95% of the synoviocytes had high-level transgene expression. Gene expression diminished to the basal level (5%) when the inflammation subsided at 30 days after LPS treatment. More importantly, the diminished transgene expression could be efficiently reactivated by a repeated insult. The transgene expression in normal joints transduced with rAAV remained low for a long period of time (30 days) but could still be induced to high levels (95%) at 3 to 7 days after LPS treatment. This is the first demonstration of disease state-regulated transgene expression. These findings strongly support the feasibility of therapeutic as well as preventative gene transfer approaches for RA with rAAV vectors containing therapeutic genes, which are expected to respond primarily to the disease state of the target tissue.

Original languageEnglish
Pages (from-to)3410-3417
Number of pages8
JournalJournal of Virology
Volume73
Issue number4
Publication statusPublished - Apr 1 1999
Externally publishedYes

Fingerprint

Dependovirus
arthritis
Transgenes
transgenes
Arthritis
lipopolysaccharides
rheumatoid arthritis
Lipopolysaccharides
rats
Rheumatoid Arthritis
Joints
Galactosidases
galactosidases
Therapeutics
vector competence
therapeutics
gene therapy
autoimmune diseases
gene transfer
Genetic Therapy

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Pan, R. Y., Xiao, X., Chen, S. L., Li, J., Lin, L. C., Wang, H-J., & Tsao, Y. P. (1999). Disease-inducible transgene expression from a recombinant adeno- associated virus vector in a rat arthritis model. Journal of Virology, 73(4), 3410-3417.

Disease-inducible transgene expression from a recombinant adeno- associated virus vector in a rat arthritis model. / Pan, Ru Yu; Xiao, Xiao; Chen, Show Li; Li, Juan; Lin, Leou Chyr; Wang, Hsian-Jenn; Tsao, Yeou Ping.

In: Journal of Virology, Vol. 73, No. 4, 01.04.1999, p. 3410-3417.

Research output: Contribution to journalArticle

Pan, RY, Xiao, X, Chen, SL, Li, J, Lin, LC, Wang, H-J & Tsao, YP 1999, 'Disease-inducible transgene expression from a recombinant adeno- associated virus vector in a rat arthritis model', Journal of Virology, vol. 73, no. 4, pp. 3410-3417.
Pan, Ru Yu ; Xiao, Xiao ; Chen, Show Li ; Li, Juan ; Lin, Leou Chyr ; Wang, Hsian-Jenn ; Tsao, Yeou Ping. / Disease-inducible transgene expression from a recombinant adeno- associated virus vector in a rat arthritis model. In: Journal of Virology. 1999 ; Vol. 73, No. 4. pp. 3410-3417.
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