Effectiveness and safety of hydrodynamic gene delivery in animals with fibrotic liver

作者: Tian Zhou

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摘要: Hydrodynamic gene delivery (HGD) has emerged as an effective and safe method for transfecting liver hepatocytes in vivo, potential therapy of fibrosis. The objective this study was to evaluate the effectiveness safety HGD using CCl4 induced fibrotic rats a model. I demonstrated that there is progressive reduction efficiency with increasing severity Using reporter plasmid containing luciferase gene, we showed over 2,000-fold decrease activity advanced fibrosis compared control animals. Reduction expression correlated lower copy number DNA less amount mRNA liver. Microscopy analysis revealed significant accumulation collagen fibers boundary lobules thickened hepatic sinusoidal endothelium. morphological changes are associated restriction flow-through across solution hydrodynamically injected responsible reduced hydrodynamic procedure. Results from electrocardiogram serum biochemistry show no difference between animals undergone HGD. These results suggest transfer but decreases increase Future work should focus on adjustment injection parameters (DNA dose, volume, speed) optimal

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