3rd Annual BMRP Investigator Meeting - Abstract

Colon-Directed Delivery of Viral Vectors Using Virus-Microbead Conjugates for Gene Therapy of Inflammatory Bowel Disease

Alan Jerusalmi, Mark W. Pandori, Samuel J. Farlow, Yuwadee Watanapokasin and Takeshi Sano^a

Center for Molecular Imaging Diagnosis and Therapy and Basic Science Laboratory, Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School (Boston, Massachusetts, U.S.A.)

In the last few years, we have developed a novel gene transfer technology that allows safe, efficient delivery of recombinant viral vectors to target sites of gene therapy.  In this technology, viral particles are attached stably to the surfaces of microbeads and then delivered to target sites in the form of virus-microbead conjugates.  Such conjugates can infect cells at efficiencies equivalent to or even greater than free viral vectors in solution.  In particular, the transduction of target cells, which are poorly permissive to infection by free viral vectors, can be considerably enhanced, providing the attached viral vectors with broader tropism.  This gene transfer technology is currently being used to develop a gene transfer strategy for inflammatory bowel disease (IBD).  We have constructed adenoviral vectors carrying the gene for mouse interleukin-10 (IL-10).  We have demonstrated by using in vitro systems that these viral vectors can produce encoded mouse IL-10 efficiently upon infection of cells.  Virus-microbead conjugates containing these viral vectors are being tested by using TNBS-induced mouse colitis models for their abilities to deliver the attached viral particles to colonic cells by enema and to produce and secrete IL-10 locally in the colon for the amelioration of colitis.  This effort is also being extended to include adeno-associated viral vectors carrying the mouse IL-10 gene as another viral vector species.

^aPrincipal Investigator