Lay Summary

Proposal No. IBD-0078
Principal Investigator:  Takeshi Sano, Ph.D.
Applicant Organization:  Beth Israel Deaconess Medical Center (Boston, Massachusetts, U.S.A.)
Project Title:  A colon-directed gene transfer technology for gene therapy of inflammatory bowel disease
Period of Award:  November 1, 2003 - October 31, 2005

An intense, local immune response is involved in the initiation and progression of inflammatory bowel disease (IBD). Thus, one potential therapeutic strategy for IBD is to repress inflammation by using anti-inflammatory cytokines. Although daily administration of certain anti-inflammatory cytokines has shown some therapeutic benefit in Crohn's disease, a few critical problems with this strategy make its application to the therapy of IBD unrealistic.

Gene therapy approaches are attractive as therapeutic strategies for IBD, since localized, longterm expression of anti-inflammatory cytokines at inflamed lesions in the colon is potentially achievable. In fact, a few recent studies have demonstrated the potential efficacy of the local delivery of the genes for anti-inflammatory cytokines to the colon as a therapeutic strategy for IBD. One genuine concern in an effort to bring this and other gene therapy approaches to the clinical stage is with the safety in using viral vectors of cytokines in human subjects. The need for a much greater attention to safety than previously considered has now become apparent for any gene therapy protocol prior to its implementation in human subjects.

This project aims to develop strategies for safe, focused virus-mediated delivery of therapeutic transgenes to inflamed lesions in the colon toward the realization of gene therapy of IBD. Particular emphasis will be placed on the safety of virus-mediated gene transfer. We have recently developed a novel gene transfer technology, which can offer enhancements of both safety and efficacy to virus-mediated gene transfer strategies. We propose to investigate the potential of this gene transfer technology for the safe, efficient, and focused delivery of the genes for anti-inflammatory factors to the colon as a therapeutic strategy for IBD. Successful completion of this proposed project should provide considerable advancements toward the realization of the gene therapy in persons suffering from IBD.