Gene transfer: from concept to therapy.

摘要

In the last few years, several novel strategies have been proposed for the treatment of rheumatoid arthritis (RA). Among them, gene therapy is considered a promising concept bearing the potential of highly specific targeting of relevant pathomechanisms. Early studies using gene transfer focused mainly on studying disease mechanisms, whereas recent research has put potential clinical applications to the forefront of attention. This has provided new answers to the question of how to deliver genes into the rheumatoid synovium as well as which pathways to target. Thus, significant progress has been made in the continued development of viral systems, including retro- and adenoviruses, as well as in the exploration of novel tools such as herpes virus-based systems or liposomes in combination with viral fusion proteins. When potential targets for gene transfer in RA are considered, two strategies have emerged: the first focuses on the delivery of secreted proteins, mainly cytokines and cytokine receptors, to inhibit inflammation in arthritic joints. Based on our growing knowledge about the pathogenesis of RA, however, there has also been substantial progress in exploring approaches that aim at interfering specifically with signaling pathways involved in the activation and apoptosis of synovial cells. The data from recent studies indicate the ability to selectively target specific disease processes by the differential expression of therapeutic genes in varying cell types and at different stages of disease, thus demonstrating the potential of gene transfer as an arthritis therapy.