Targeted Delivery of Recombinant Adenovirus to Gut

Inflammatory bowel disease (IBD) is a collective term that includes Crohn's disease andulcerative colitis. Although both disorders have a distinct clinical course with characteristicpathophysiology, the destructive and progressive course of IBD probably is due to persistent elevatedexpression of interleukin-1 (IL-1) by macrophages in the bowel of affected patients. IL-1, a centralmediator of inflammation responsible for initiating a host of immunologic events, is a logical target foranti-inflammatory therapies in IBD. Current drug therapies are directed at amelio-rating the effects ofIL-1. However, the therapies are not always effective and are associated with untoward side effects.Our long term objective is to develop an alternative therapy, oral formulations of recombinant adenoviralvectors containing the transgene for interleukin-1 receptor antagonist protein (IL-1ra). This vector isbiologically active both in vitro and in vivo, and is capable of expressing therapeutic levels of IL-1ra. Thisinitial phase will examine the efficiency and duration of IL-1ra gene expression following adenoviralmediated gene transfer to normal rat ileum.