August 1, 1993Journal of Clinical Investigation185 citationsOpen Access
Adenoviral-mediated gene transfer to rabbit synovium in vivo.
Key Result
Intraarticular injection of a recombinant adenoviral vector resulted in high-efficiency gene transfer and continued expression of beta-galactosidase in rabbit synoviocytes for up to 8 weeks.
Structured PICO
Does intraarticular injection of recombinant adenoviral vectors result in efficient gene transfer and expression in rabbit synovium in vivo?
P
Population
7 male New Zealand white rabbits used as an in vivo model to evaluate adenoviral-mediated gene transfer to synovial tissues over 8 weeks.
I
Intervention
Intraarticular injection of 1 ml of purified recombinant adenoviral vector containing the gene for E. coli beta-galactosidase (AdCMVlacZ) into the right hind knee
C
Comparator
Left knee either left uninjected (n=3) or injected with control vector AdCSV (n=4)
O
Outcome
Transgenic lacZ expression in synovial tissues assessed by in situ staining, immunohistochemistry, and transmission electron microscopysurrogate
Recombinant adenoviral vectors can efficiently transduce synovial lining cells in vivo, suggesting a potential method for gene therapy in inflammatory arthropathies.
Limitations
- Small number of animals examined
- Progressive decline in lacZ expression observed in vivo over time
- Development of a systemic humoral immune response against adenoviral structural proteins and the transgene
Abstract
Currently, treatment for rheumatoid arthritis and other inflammatory arthropathies is often ineffective in ameliorating the progression of the disease, particularly the invasive destruction of cartilage and bone by rheumatoid synovium. Multiple aspects of this inflammatory process are mediated by the synovial lining cells (synoviocytes). Genetic modification of these cells in vivo represents a potential method for the treatment of these conditions. In this report, we describe a novel technique for the genetic transduction of synovial lining cells in vivo using recombinant adenoviral vectors and intraarticular injection techniques. Purified high titer suspensions of a recombinant adenoviral vector containing the gene for Escherichia coli beta-galactosidase (AdCMVlacZ) were directly injected into the hind knees of New Zealand white rabbits. Synovial tissues were then examined for transgenic lacZ expression using a combination of in situ staining for beta-galactosidase activity, immunohistochemical staining, and transmission electron microscopy. High efficiency gene transfer and lacZ expression was observed in both type A and type B synoviocytes throughout the articular and periarticular synovium of the rabbit knee, with continued expression of transgenic lacZ detected for > or = 8 wk after infection.
Cite This Study
Roessler et al. (Sun,) conducted a other in Normal synovial tissue (model for gene therapy in inflammatory arthropathies) (n=7). AdCMVlacZ (recombinant adenoviral vector) vs. Uninjected or AdCSV (control vector) was evaluated on Transgenic lacZ expression in synovial lining cells. Intraarticular injection of a recombinant adenoviral vector resulted in high-efficiency gene transfer and continued expression of beta-galactosidase in rabbit synoviocytes for up to 8 weeks.