Schematic presentation of the various gene therapeutic approaches that are used in experimental models of rheumatoid arthritis. We discriminate cytokine targeting and cell targeting as the two main gene therapeutic approaches to arthritis. In cytokine targeting, the objective is to restore the (local) cytokine balance in arthritis in order to silence the inflammatory process and/or to stop the destruction of cartilage and bone. Cell targeting is the elimination of cells from the inflamed joint in order to silence the disease. Genetic synovectomy is the strategy of killing transformed synovial fibroblasts with a connective tissue aggressive phenotype. Selective cell targeting of antigen-specific lymphocytes has major consequences for the inflammatory process, and inhibition of angiogenesis results in reduced pannus formation and synovial hyperplasia. The numbers in brackets indicate reference numbers. CTLA4, cytotoxic lymphocyte antigen 4; FasL, Fas ligand; HSV, herpes simplex virus; IKKβ, IκB kinase-β; IκBαDN, IκBα dominant negative; IL-1R, interleukin-1 receptor; IL-1Ra, IL-1 receptor antagonist; IL-1RAcP, IL-1 receptor accessory protein; IL-18BPc, IL-18 binding protein c; NFκB, nuclear factor-κB; ODN, oligonucleotides; SOCS, suppressor of cytokine signalling; TACI, transmembrane activator and calcium modulator and cyclophilin ligand interactor; TK, thymidine kinase; TNF, tumour necrosis factor; TRAIL, TNF-related apoptosis inducing ligand; VEGFR, vascular endothelial growth factor receptor; vIL-10, viral IL-10; TGF, transforming growth factor. The strategy to protect cartilage and chondrocytes in arthritis given in this illustration are reviewed in detail by van der Kraan and coworkers  and by Evans and coworkers .
van de Loo et al. Arthritis Res Ther 2004 6:183-196 doi:10.1186/ar1214