Title

Scaav-Mediated Gene Transfer Of Interleukin-1-Receptor Antagonist To Synovium And Articular Cartilage In Large Mammalian Joints

Keywords

Cartilage; Equine; Interleukin-1-receptor antagonist; Osteoarthritis; Self-complementary adeno-associated virus; Synovium

Abstract

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. © 2013 Macmillan Publishers Limited All rights reserved.

Publication Date

6-1-2013

Publication Title

Gene Therapy

Volume

20

Issue

6

Number of Pages

670-677

Document Type

Article

Personal Identifier

scopus

DOI Link

https://doi.org/10.1038/gt.2012.81

Socpus ID

84882288958 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/84882288958

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