I read with interest Eugene Russo's article on regulated gene therapy.1 For the past six years, I have been developing a system to target genes to specific tissues and regulate their expression using hypoxia response enhancer elements. By combining tissue-specific promoter elements and strategically placed hypoxia responsive enhancers, we can now target genes to almost any organ and have the expression of the target gene limited quite tightly to periods during and immediately following ischemia. I propose that this method will be applicable for therapeutic gene targeting to a number of ischemia-related diseases, including myocardial ischemia, stroke, retinopathies associated with diabetes, and possibly solid tumors where hypoxia-regulated antiangiogenic genes may be delivered to the vascular endothelium to prevent tumor neovascularization. I also contend that this type of regulated gene therapy will be preferable in many circumstances to that described by Russo, because the transgenes in our method are regulated...

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