Enhanced gene transfer to arthritic joints using adeno-associated virus type 5: implications for intra-articular gene therapy. Issue 12 (5th May 2005)

• Record Type: Journal Article
• Authors: Adriaansen, J; Tas, S W; Klarenbeek, P L; Bakker, A C; Apparailly, F; Firestein, G S; Jorgensen, C; Vervoordeldonk, M J B M; Tak, P P
• Is Part Of: Annals of the rheumatic diseases. Volume 64:Issue 12(2005)
• Page Start: 1677
• Page End: 1684
• Publication Date: 2005-05-05
• Subjects: AIA, adjuvant induced arthritis -- CMV, cytomegalovirus -- FLS, fibroblast-like synoviocytes -- GC, genomic copies -- gDNA, genomic DNA -- GAPDH, glyceraldehyde-3-phosphate dehydrogenase -- GFP, green fluorescent protein -- IOD, integrated optical density -- MOD, mean optical density -- PBS, phosphate buffered saline -- PCR, poymerase chain reaction -- RA, rheumatoid arthritis -- rAAV, recombinant adeno-associated virus; adeno-associated virus -- serotypes -- rheumatoid arthritis -- synovium -- gene therapy; Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/ard.2004.035063
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Background: Gene therapy of the joint has great potential as a new therapeutic approach for the treatment of rheumatoid arthritis (RA). The vector chosen is of crucial importance for clinical success. Objective: To investigate the tropism and transduction efficiency in arthritic joints in vivo, and in synovial cells in vitro, using five different serotypes of recombinant adeno-associated virus (rAAV) encoding β-galactosidase or green fluorescent protein genes. Methods: rAAV was injected into the ankle joints of rats with adjuvant arthritis after the onset of disease. Synovial tissue was examined at different time points for β-galactosidase protein and gene expression by in situ staining and polymerase chain reaction (PCR) analysis, respectively. In addition, the ability of rAAV to transduce primary human fibroblast-like synoviocytes from patients with RA was investigated in vitro. Results: Intra-articular injection of the rAAV5 serotype resulted in the highest synovial transduction, followed by much lower expression using rAAV2. Expression of the transgene was already detectable 7 days after injection and lasted for at least 4 weeks. Only background staining was seen for serotypes 1, 3, and 4. Importantly, there was a minimal humoral immune response to rAAV5 compared with rAAV2. Additionally, it was found that both rAAV2 and rAAV5 can efficiently transduce human fibroblast-like synoviocytes obtained from patients with RA. Conclusion: Intra-articular rAAV mediated gene therapy in RA might be improved by using rAAV5 rather than other serotypes.