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Arthritis2012; 2012; 735472; doi: 10.1155/2012/735472

Inflammation and immune response of intra-articular serotype 2 adeno-associated virus or adenovirus vectors in a large animal model.

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.
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Publication Date: 2012-01-11 PubMed ID: 22288012PubMed Central: PMC3263587DOI: 10.1155/2012/735472Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This study explores the potential of intra-articular gene therapy for the treatment of osteoarthritis and rheumatoid arthritis. Specifically, the researchers compared the effects of adenovirus vectors, serotype 2 adeno-associated virus vectors, and self-complementary AAV2 vectors on equine cells. They found that scAAV2 demonstrated greater efficiency and persistence, and produced less inflammation than the other vectors, making them a promising avenue for therapeutic use.

Introduction

  • The research is centered around testing different methods of intra-articular gene therapy, which is a potential treatment for osteoarthritis and rheumatoid arthritis.
  • Intra-articular gene therapy involves injecting genetic material, delivered via a vector like a virus, into the joints affected by the disease.
  • The vectors assessed in this study include adenovirus vectors (Ad), serotype 2 adeno-associated virus vectors (rAAV2), and self-complementary (sc) AAV2 vectors – all containing the gene for green fluorescent protein (GFP).

Methods

  • The scientists conducted experiments both in vitro (on cells in a controlled laboratory setting) and in vivo (on live horses).
  • In the in vitro experiment, equine chondrocytes (cartilage cells) and synovial cells (cells that produce joint fluid) were exposed to the different vectors.
  • In the in vivo experiment, the joints of six horses were injected with the three types of vectors.
  • The results were analyzed based on the efficiency of gene transduction (how well the GFP gene was taken up and expressed by the cells) and any inflammation or immune response (as measured by neutralizing antibody (NAb) titer in horse’s serum and joint fluid).

Results

  • The in vitro experiment showed that the scAAV2 vectors performed the best, achieving more efficient transduction and sustained gene expression.
  • Pin vivo, the Ad vectors caused more joint inflammation than the AAV2 vectors. However, the levels of neutralizing antibodies, indicative of an immune response, were similar for the Ad and AAV2 vectors.

Conclusion

  • Based on their findings, the researchers concluded that scAAV2 vectors could potentially be superior for intra-articular gene therapy. This is mainly due to their high transduction rates and low inflammation.
  • Both rAAV2 and scAAV2 vectors were demonstrated to be safer for intra-articular use than Ad vectors due to causing less inflammation. Hence, using these AAV2-derived vectors could be a more effective approach when developing gene therapies for osteoarthritis and rheumatoid arthritis.

Cite This Article

APA
Ishihara A, Bartlett JS, Bertone AL. (2012). Inflammation and immune response of intra-articular serotype 2 adeno-associated virus or adenovirus vectors in a large animal model. Arthritis, 2012, 735472. https://doi.org/10.1155/2012/735472

Publication

Arthritis
ISSN: 2090-1992
NlmUniqueID: 101566207
Country: United States
Language: English
Volume: 2012
Pages: 735472
PII: 735472

Researcher Affiliations

Ishihara, Akikazu
  • Comparative Orthopedic Research Laboratories, Department of Veterinary Clinical Sciences, The Ohio State University, 1900 Coffey Road, Columbus, OH 43210, USA.
Bartlett, Jeffrey S
    Bertone, Alicia L

      Grant Funding

      • K08 AR049201 / NIAMS NIH HHS

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