1887

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Volume 88, Issue 6

Local delivery of beta interferon using an adeno-associated virus type 5 effectively inhibits adjuvant arthritis in rats Free

Abstract

Beta interferon (IFN-) is a cytokine with potent immunomodulatory properties and has been described as a promising therapeutic molecule for the treatment of rheumatoid arthritis (RA). IFN- was previously overexpressed intra-articularly using an adenoviral vector in rats with adjuvant arthritis (AA) as a model of RA. This effect was powerful, albeit transient due to the vector chosen. Therefore, in the context of pre-clinical development, a delivery vector optimized for intra-articular gene transfer, recombinant adeno-associated virus type 5 (rAAV5), was selected. To exert an optimal effect, protein production should parallel the course of the disease. For this reason, the gene for IFN- was placed under the control of an inflammation-responsive [nuclear factor (NF)-B] promoter. After intra-articular injection of the rAAV5 constructs in rats with AA, local transcription of the transgene and production of the IFN- protein was found, leading to a pronounced and sustained effect on paw swelling when the expression was under the control of the NF-B-responsive promoter. Additionally, a significant beneficial effect was observed on proteoglycan depletion and erosions. Thus, intra-articular overexpression of IFN- using a rAAV5 vector exhibits potential as an innovative therapy for the treatment of RA.

  • Received:
  • Accepted:
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2007-06-01
2024-04-20
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Local delivery of beta interferon using an adeno-associated virus type 5 effectively inhibits adjuvant arthritis in rats
J. Gen. Virol. 88, 1717 (2007); https://doi.org/10.1099/vir.0.82603-0
/content/journal/jgv/10.1099/vir.0.82603-0
/content/journal/jgv/10.1099/vir.0.82603-0
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