Ex vivo gene transfer in the years to come.docVIP

Available online /content/4/1/010 Commentary Ex vivo gene transfer in the years to come Thomas Pap*?, Renate E Gay?, Ulf Müller-Ladner? and Steffen Gay? *Division of Experimental Rheumatology, Center of Internal Medicine, University Hospital Magdeburg, Germany ?Center of Experimental Rheumatology, Department of Rheumatology, University Hospital Zurich, Switzerland ?Department of Internal Medicine I, University Hospital Regensburg, Germany Correspondence: Thomas Pap, MD, Division of Experimental Rheumatology, Center of Internal Medicine, University Hospital Magdeburg, Leipziger Str. 44, D-39120 Magdeburg. Tel: +49 (0)391 6713314; fax: +49 (0)391 6715447; e-mail: thomas.pap@medizin.uni-magdeburg.de Received: 14 August 2001 Accepted: 19 September 2001 Published: 9 October 2001 Arthritis Res 2002, 4:10-12 ? 2002 BioMed Central Ltd (Print ISSN 1465-9905; Online ISSN 1465-9913) Abstract Synovial fibroblasts (SFs) have become a major target for ex vivo gene transfer in rheumatoid arthritis (RA), but efficient transduction of RA-SFs still is a major problem. The low proliferation rate and heterogeneity of RA-SFs, together with their lack of highly specific surface receptors, have hampered a more extensive application of this technique. Improving transduction protocols with conventional viral vectors, therefore, as well as developing novel strategies, such as alternative target cells, and novel delivery systems constitute a major challenge. Recent progress in this field will lead to the achievement of high transgene expression, and will facilitate the use of gene transfer in human trials. Keywords: ex vivo approach, gene therapy, rheumatoid arthritis, viral vector Introduction exceed it when constructs are used that result in integra- tion into the genome. It is now well established that successful approaches to gene transfer in rheumatoid arthritis (RA) require three main questions to be answered. What genes or gene con-