| Autor: |
Watson RS; Department of Orthopaedics and Rehabilitation, University of Florida, Gainesville, FL 32608-0137, USA., Broome TA, Levings PP, Rice BL, Kay JD, Smith AD, Gouze E, Gouze JN, Dacanay EA, Hauswirth WW, Nickerson DM, Dark MJ, Colahan PT, Ghivizzani SC |
| Jazyk: |
angličtina |
| Zdroj: |
Gene therapy [Gene Ther] 2013 Jun; Vol. 20 (6), pp. 670-7. Date of Electronic Publication: 2012 Nov 15. |
| DOI: |
10.1038/gt.2012.81 |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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