In vitro gene transfer to chondrocytes and synovial fibroblasts by adenoviral vectors.
The major requirement of a successful gene transfer is the efficient delivery of an exogenous therapeutic gene to the appropriate cell type with subsequent high or regulated levels of expression. In this context, viral systems are more efficient than nonviral systems, giving higher levels of gene expression for longer periods. For the application of osteoarthritis (OA), gene products triggering anti-inflammatory or chondroprotective effects are of obvious therapeutic utility. Thus, their cognate genes are candidates for use in the gene therapy of OA. In this chapter, we describe the preparation, the use, and the effect of the transduction of chondrocytes or synovial fibroblasts with an adenoviral vector encoding the cDNA for glutamine: fructose-6-phosphate amidotransferase (GFAT). This is intended to serve as an example of a technology that can be used to evaluate the biological effects of overexpression of other cDNAs.
Center for Molecular Orthopaedics, Harvard Medical School, Boston, MA, USA.
Jean-Noel
JN
Gouze
Martin J
MJ
Stoddart
Elvire
E
Gouze
Glyn D
GD
Palmer
Steven C
SC
Ghivizzani
Alan J
AJ
Grodzinsky
Christopher H
CH
Evans
D000256:Adenoviridae / Q000737:chemistry / Q000235:genetics*; D002358:Cartilage, Articular / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D019902:Chondrocytes / Q000737:chemistry / Q000378:metabolism*; D004274:DNA, Recombinant / Q000737:chemistry / Q000235:genetics; D005347:Fibroblasts / Q000737:chemistry / Q000378:metabolism*; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000737:chemistry / Q000235:genetics*; D005945:Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing) / Q000235:genetics; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis; D010003:Osteoarthritis / Q000235:genetics / Q000628:therapy; D010957:Plasmids / Q000737:chemistry / Q000235:genetics; D013583:Synovial Membrane / Q000166:cytology*; D014161:Transduction, Genetic / Q000379:methods*
D004274:DNA, Recombinant; D007375:Interleukin-1; D009569:Nitric Oxide; D005945:Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing)