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Arthritis
Volume 2012 (2012), Article ID 735472, 8 pages
http://dx.doi.org/10.1155/2012/735472
Research Article

Inflammation and Immune Response of Intra-Articular Serotype 2 Adeno-Associated Virus or Adenovirus Vectors in a Large Animal Model

1Comparative Orthopedic Research Laboratories, Department of Veterinary Clinical Sciences, The Ohio State University, 1900 Coffey Road, Columbus, OH 43210, USA
2Gene Therapy Center, The Research Institute at Nationwide Children's Hospital, Columbus, OH 43205, USA
3Department of Pediatrics, The Ohio State University, Columbus, OH 43205, USA

Received 23 August 2011; Accepted 5 October 2011

Academic Editor: Peter M. van der Kraan

Copyright © 2012 Akikazu Ishihara et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Intra-articular gene therapy has potential for the treatment of osteoarthritis and rheumatoid arthritis. To quantify in vitro relative gene transduction, equine chondrocytes and synovial cells were treated with adenovirus vectors (Ad), serotype 2 adeno-associated virus vectors (rAAV2), or self-complementary (sc) AAV2 vectors carrying green fluorescent protein (GFP). Using 6 horses, bilateral metacarpophalangeal joints were injected with Ad, rAAV2, or scAAV2 vectors carrying GFP genes to assess the in vivo joint inflammation and neutralizing antibody (NAb) titer in serum and joint fluid. In vitro, the greater transduction efficiency and sustained gene expression were achieved by scAAV2 compared to rAAV2 in equine chondrocytes and synovial cells. In vivo, AAV2 demonstrated less joint inflammation than Ad, but similar NAb titer. The scAAV2 vectors can induce superior gene transduction than rAAV2 in articular cells, and both rAAV2 and scAAV2 vectors were showed to be safer for intra-articular use than Ad vectors.