| scAAV-mediated gene transfer of interleukin-1-receptor antagonist to synovium and articular cartilage in large mammalian joints. | |
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MedLine Citation:
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PMID: 23151520 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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With the long-term goal of developing a gene-based treatment for osteoarthritis (OA), we performed studies to evaluate the equine joint as a model for adeno-associated virus (AAV)-mediated gene transfer to large, weight-bearing human joints. A self-complementary AAV2 vector containing the coding regions for human interleukin-1-receptor antagonist (hIL-1Ra) or green fluorescent protein was packaged in AAV capsid serotypes 1, 2, 5, 8 and 9. Following infection of human and equine synovial fibroblasts in culture, we found that both were only receptive to transduction with AAV1, 2 and 5. For these serotypes, however, transgene expression from the equine cells was consistently at least 10-fold higher. Analyses of AAV surface receptor molecules and intracellular trafficking of vector genomes implicate enhanced viral uptake by the equine cells. Following delivery of 1 × 10(11) vector genomes of serotypes 2, 5 and 8 into the forelimb joints of the horse, all three enabled hIL-1Ra expression at biologically relevant levels and effectively transduced the same cell types, primarily synovial fibroblasts and, to a lesser degree, chondrocytes in articular cartilage. These results provide optimism that AAV vectors can be effectively adapted for gene delivery to large human joints affected by OA.Gene Therapy advance online publication, 15 November 2012; doi:10.1038/gt.2012.81. |
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Authors:
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R S Watson; T A Broome; P P Levings; B L Rice; J D Kay; A D Smith; E Gouze; J-N Gouze; E A Dacanay; W W Hauswirth; D M Nickerson; M J Dark; P T Colahan; S C Ghivizzani |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-11-15 |
Journal Detail:
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Title: Gene therapy Volume: - ISSN: 1476-5462 ISO Abbreviation: Gene Ther. Publication Date: 2012 Nov |
Date Detail:
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Created Date: 2012-11-15 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9421525 Medline TA: Gene Ther Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Orthopaedics and Rehabilitation, University of Florida, Gainesville, FL, USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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