Exploiting hypoxia for targeted gene therapy

Abstract

The ability to deliver a therapeutic gene to the correct disease location and achieve expression at a relevant therapeutic level is important for the development of safe and potent gene-based therapies. Tissue-specific promoters restrict gene expression spatially in a cell-specific manner whereas pharmacologically responsive promoters can be controlled temporally through the administration of chemical repressors or activators. In some disease conditions such as cancer, it may be beneficial to restrict gene expression to a particular subset of diseased cells whilst preventing gene expression in the healthy portions of the tissue. This review focuses on the in vitro and in vivo studies which have fuelled the emergence of physiological regulation as an attractive means of spatially and temporally targeting gene expression. This review will centre on exploiting the physiological feature of hypoxia to target and control gene expression highlighting the recent success of hypoxia regulated gene therapy vectors in models of chronic anaemia and cancer.