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Updated: Aug 18, 2026
Subconjunctival Administration of Adeno-associated Virus Vectors in Small Animal Models
Published on: March 16, 2022
Enhanced gene transfer to arthritic joints using adeno-associated virus type 5: implications for intra-articular gene
J Adriaansen1, S W Tas, P L Klarenbeek
1Division of Clinical Immunology and Rheumatology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
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 beta-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 beta-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.
