A novel endothelial cell-based gene therapy platform for the in vivo delivery of apolipoprotein E

A major focus in gene therapy has been the use of recombinant viruses to de liver genes in vivo. Although this approach shows much promise, there are m any safety concerns associated with the use of viral materials in the treat ment of human diseases. Our alternative cell-based gene therapy approach ut ilizes endothelial cells (Pro 175) isolated from the murine embryonic yolk sac. These endothelial cells were evaluated for their potential use in gene therapy as a gene delivery platform. As a test model, we used these cells to deliver apolipoprotein E (apoE) in the murine apoE knockout atherosclero sis model. The lack of apoE protein in these animals results in high levels of serum cholesterol and formation of severe aortic plaques and lesions at a young age. After transplantation of the apoE secreting Pro 175 endotheli al cells into apoE-deficient mice, serum cholesterol levels were measured a t 2 week intervals. During the 3 months after the initiation of these exper iments, levels of cholesterol in the animals having received the apoE secre ting endothelial cells were statistically lower compared with the levels of age-matched controls having received non-secreting endothelial cells. Conc omitant with cholesterol reduction, atherosclerotic aortic plaques were not iceably reduced in the experimental apoE+ animals. These results highlight the potential of these unique endothelial cells as an efficient delivery pl atform for somatic gene therapy.