Gene transfer: from concept to therapy

In the last few years, several novel strategies have been proposed for the treatment of rheumatoid arthritis (RA). Among them, gene therapy is conside red a promising concept bearing the potential of highly specific targeting of relevant pathomechanisms. Early studies using gene transfer focused main ly on studying disease mechanisms, whereas recent research has put potentia l clinical applications to the forefront of attention. This has provided ne w answers to the question of how to deliver genes into the rheumatoid synov ium as well as which pathways to target. Thus, significant progress has bee n made in the continued development of viral systems, including retro- and adenoviruses, as well as in the exploration of novel tools such as herpes v irus-based systems or liposomes in combination with viral fusion proteins. When potential targets for gene transfer in RA are considered, two strategi es have emerged: the first focuses on the delivery of secreted proteins, ma inly cytokines and cytokine receptors, to inhibit inflammation in arthritic joints. Based on our growing knowledge about the pathogenesis of RA, howev er, there has also been substantial progress in exploring approaches that a im at interfering specifically with signaling pathways involved in the acti vation and apoptosis of synovial cells. The data from recent studies indica te the ability to selectively target specific disease processes by the diff erential expression of therapeutic genes in varying cell types and at diffe rent stages of disease, thus demonstrating the potential of gene transfer a s an arthritis therapy. Curr Opin Rheumatol 2000, 12:205-210 (C) 2000 Lippi ncott Williams & Wilkins, Inc.