A tropism-modified adenoviral vector increased the effectiveness of gene therapy for arthritis

A. C. Bakker, F. A.J. Van De Loo, L. A.B. Joosten, M. B. Bennink, O. J. Arntz, I. P. Dmitriev, E. A. Kashentsera, D. T. Curiel, W. B. Van Den Berg

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Adenoviral vectors (AdV) are used for anti-inflammatory cytokine therapy in experimental arthritis. Cell entry of AdV is dependent on the initial recognition of the coxsackie-adenovirus receptor (CAR) on cells. Recently, an Arg-Gly-Asp (RGD) motif was introduced in the HI loop of the fiber knob, this enables the adenovirus to bypass CAR and mediate cell entry via RGD binding integrins. In this study, we explored the transduction efficiency of the RGD-modified adenovirus in synovium and compared the RGD-modified with the conventional adenoviral vector for their effectiveness to modulate the murine collagen-induced arthritis (CIA) model when used to overexpress mlL-1Ra in the knee joint. Twenty-four hours after intra-articular injection of 107 fluorescent forming units (ffu) virus, luciferase (luc) activity in Ad5LucRGD-injected joints was up to 38 times higher than in AdCMVLuc-injected joints, and in arthritic joints the transduction efficiency was up to 69 times higher for the Ad5LucRGD viruses. Transduction of the synovial lining by the RGD-modified adenovirus containing the mlL-1Ra transgene, markedly improved the inhibition of CIA compared with the conventional virus in both a prophylactic and therapeutic treatment protocol. These results show that targeting integrins with the RGD-modified AdV improved the outcome of gene therapy for arthritis.

Original languageEnglish
Pages (from-to)1785-1793
Number of pages9
JournalGene therapy
Volume8
Issue number23
DOIs
StatePublished - Jan 1 2001
Externally publishedYes

Keywords

  • Adenovirus
  • Arthritis
  • CIA
  • RGD
  • Synovium
  • mCAR

Fingerprint Dive into the research topics of 'A tropism-modified adenoviral vector increased the effectiveness of gene therapy for arthritis'. Together they form a unique fingerprint.

  • Cite this

    Bakker, A. C., Van De Loo, F. A. J., Joosten, L. A. B., Bennink, M. B., Arntz, O. J., Dmitriev, I. P., Kashentsera, E. A., Curiel, D. T., & Van Den Berg, W. B. (2001). A tropism-modified adenoviral vector increased the effectiveness of gene therapy for arthritis. Gene therapy, 8(23), 1785-1793. https://doi.org/10.1038/sj.gt.3301612