Non-invasive viral gene transfer of factor IX to colonic epithelial cells in hemophilia B mice.

摘要

Gene therapy is potentially an ideal therapeutic strategy for the treatment of hemophilia B. In recent studies, hepatocytes, skeletal muscle, endothelial cells, bone marrow stroma cells, as well as other cell types, have been targeted for gene transfer [1-3]. However, the routine routes of administration of viral vectors include intravenous infusion, intramuscular injection and hypodermic embedment [4-6], which are invasive and carry the risk of both bleeding and infection. For this reason, a potentially non-invasive strategy may be to target colon-epithelial cells via an enema to deliver a recombinant adeno-associated viral vector serotype 2 (rAAV2) that encodes human factor (F) IX (hFIX). To this end we selected the gut epithelium as a target cell hFIX gene transfer, and analyzed the effects of this both in vitro and in vivo.