Accepted: 9 April 2003 Published online: 25 June 2003 © Springer-Verlag 2003 Abstract Background: Local ex- pression of anti-inflammatory or im- munoregulatory genes may offer an alternative treatment of gastrointesti- nal inflammation. Discussion: We review the basic requirements for gene therapy, the possible routes of delivery, and the different strategies for specific targeting focusing on gastrointestinal inflammation. Keywords Gene therapy · Gastrointestinal inflammation · Retroviral vector · Interleukin-10 Int J Colorectal Dis (2004) 19:79–86 DOI 10.1007/s00384-003-0501-4 REVIEW Catherine van Montfrans Anje A. te Velde Sander J. H. van Deventer Maria Sol Rodriguez Pena Gene therapy in the treatment of intestinal inflammation Introduction Inflammation is a major feature in a vast number of gas- trointestinal (GI) diseases, such as inflammatory bowel disease, cystic fibrosis [1], familial adenomatous polypo- sis [2], ischemia/reperfusion [3], radiation enteritis [4], Barret’s esophagus [5], celiac disease [6, 7], and Helico- bacter pylori infection [8]. Although the inflammatory changes are usually confined to the gut mucosa, most medical therapies make use of the systemic administra- tion of drugs that often have severe side effects. We pro- pose an alternative approach to the delivery of specific immunomodulatory signals to the gut mucosa, using gene transfer. Although gene therapy was initially devel- oped for the treatment of monogenic diseases, nowadays most of the approved clinical protocols involve cancer patients [9]. More recently the possibility of treating in- flammatory diseases by delivery of anti-inflammatory or immunomodulatory genes has attracted significant inter- est [10]. This review summarizes the various strategies for us- ing gene therapy in the treatment of GI inflammation, fo- cusing on retroviral gene transfer (for a review of adeno- viral mediated gene transfer see [11]). Requirements for gene therapy Gene therapy is the transfer of genetic material to cells with the aim of offering therapeutic benefit. The gene of interest (transgene) is transferred to the target cell by a delivery vehicle (vector), obtaining) selective gene ex- pression at the site of interest. Gene of interest The choice of a target gene is a difficult task in inflam- matory processes such as GI inflammation. Indeed, GI inflammation involves numerous genes, some of which directly modulate the expression pattern of inflammatory cells (e.g., transcription factors) while others code for proteins required for antigen presentation, for response to costimulatory molecules, for cell recruitment via che- motaxis and cell adhesion, and for more general down- stream effector functions. Examples of potential trans- genes are provided in Table 1. Anti-inflammatory cytokines such as interleukin (IL) 10 provide potential powerful tools for therapeutic inter- vention in CD. IL-10 is an anti-inflammatory cytokine C. van Montfrans · A. A. te Velde S. J. H. van Deventer M. S. Rodriguez Pena ( ✉ ) Department of Experimental Internal Medicine, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands e-mail: m.s.rodriguezpena@wanadoo.nl Tel.: +31-20-4196848 Fax: +31-20-4196848