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Gene therapy with an improved doxycycline-regulated plasmid encoding a tumour necrosis factor-alpha inhibitor in experimental arthritis

Gene therapy with an improved doxycycline-regulated plasmid encoding a tumour necrosis factor-alpha inhibitor in experimental arthritis David Gould, Nasim Yousaf, Rewas Fatah, Maria Cristina Subang and Yuti Chernajovsky Bone and Joint Research Unit, Barts and The London, Queen Mary's School of Medicine and Dentistry, Charterhouse Square, University of London, London, EC1M 6BQ, UK Corresponding author: David Gould, d.j.gould@qmul.ac.uk Received: 25 Sep 2006 Revisions requested: 26 Oct 2006 Revisions received: 20 Dec 2006 Accepted: 25 Jan 2007 Published: 25 Jan 2007 Arthritis Research & Therapy 2007, 9:R7 (doi:10.1186/ar2113) This article is online at: http://arthritis-research.com/content/9/1/R7 © 2007 Gould et al.; licensee BioMed Central Ltd | Available online http arthritis-research.eom content 9 1 R7 Research article Gene therapy with an improved doxycycline-regulated plasmid encoding a tumour necrosis factor-alpha inhibitor in experimental arthritis David Gould Nasim Yousaf Rewas Fatah Maria Cristina Subang and Yuti Chernajovsky Bone and Joint Research Unit Barts and The London Queen Mary s School of Medicine and Dentistry Charterhouse Square University of London London EC1M 6BQ UK Corresponding author David Gould d.j.gould@qmul.ac.uk Received 25 Sep 2006 Revisions requested 26 Oct 2006 Revisions received 20 Dec 2006 Accepted 25 Jan 2007 Published 25 Jan 2007 Arthritis Research Therapy 2007 9 R7 doi 10.1186 ar2113 This article is online at http arthritis-research.com content 9 1 R7 2007 Gould et al. licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License http creativecommons.org licenses by 2.0 which permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited. Open Access Abstract Inhibition of tumour necrosis factor TNF -alpha with biological molecules has proven an effective treatment for rheumatoid arthritis achieving a 20 improvement in American College of Rheumatology score in up to 65 of patients. The main drawback to these and many other biological treatments has been their expense which has precluded their widespread application. Biological molecules could alternatively be delivered by gene therapy as the encoding DNA. We have developed novel plasmid vectors termed pGTLMIK and pGTTMIK from which luciferase and a dimeric TNF receptor II dTNFR are respectively expressed in a doxycycline Dox -regulated manner. Regulated expression of luciferase from the self-contained plasmid pGTLMIK was examined in vitro in a variety of cell lines and in vivo following intramuscular delivery with electroporation in DBA 1 mice. Dox-regulated expression of luciferase from pGTLMIK of .