Title

scAAV-mediated gene transfer of interleukin-1-receptor antagonist to synovium and articular cartilage in large mammalian joints

Authors

Authors

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

Comments

Authors: contact us about adding a copy of your work at STARS@ucf.edu

Abbreviated Journal Title

Gene Ther.

Keywords

osteoarthritis; self-complementary adeno-associated virus; interleukin-1-receptor antagonist; synovium; cartilage; equine; ADENOASSOCIATED VIRUS AAV; LAMININ RECEPTOR; IN-VIVO; ARTHRITIS; VECTORS; DELIVERY; THERAPY; TRANSDUCTION; EXPRESSION; OSTEOARTHRITIS; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental

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 x 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.

Journal Title

Gene Therapy

Volume

20

Issue/Number

6

Publication Date

1-1-2013

Document Type

Article

DOI Link

http://dx.doi.org/10.1038/gt.2012.81

Language

English

First Page

670

Last Page

677

WOS Identifier

WOS:000319976600010

ISSN

0969-7128

Recommended Citation

"scAAV-mediated gene transfer of interleukin-1-receptor antagonist to synovium and articular cartilage in large mammalian joints" (2013). Faculty Bibliography 2010s. 4847.
https://stars.library.ucf.edu/facultybib2010/4847