Ex vivo serotype-specific transduction of equine joint tissue by self-complementary adeno-associated viral vectors.
Cell transplantation for the treatment of joint disease is an important clinical tool. Genetic modification of cells before transplantation has shown enhanced healing. Ex vivo genetic modification of joint tissue cells with various adeno-associated virus (AAV) serotypes has not been investigated. The transduction efficiencies of self-complementary AAV serotypes (1-6 and 8) were determined in joint tissue containing chondrocytes and synoviocytes isolated from equine models. When comparing scAAV serotypes for efficient transduction ex vivo, in chondrocytes versus synoviocytes, serotypes 6 and 2, and serotypes 3 and 2, respectively, appeared superior for gene expression. Unlike adenoviral vectors, no upregulation of inflammatory markers, such as matrix metalloproteinases and aggrecanase, was seen on treatment of joint tissue with AAV vectors ex vivo. Our findings also corroborate that ex vivo transduction of joint tissue can result in high transgene protein levels over time, and transplantation modalities might be feasible using AAV vectors in the treatment of joint-related diseases.
Goodrich
L R
LR
Orthopaedic Research Center, College of Veterinary Medicine, Colorado State University, Fort Collins, CO 80523, USA.
Choi
V W
VW
Carbone
B A Duda
BA
McIlwraith
C W
CW
Samulski
R J
RJ
D000818:Animals; D019902:Chondrocytes / Q000166:cytology* / Q000637:transplantation; D000229:Dependovirus / Q000145:classification* / Q000235:genetics; D005822:Genetic Vectors / Q000145:classification* / Q000235:genetics; D006736:Horses; D012703:Serotyping; D013583:Synovial Membrane / Q000166:cytology* / Q000637:transplantation; D014161:Transduction, Genetic / Q000379:methods*