Smith R M, Wu G Y
Department of Medicine, University of Connecticut School of Medicine, Farmington, USA.
Semin Liver Dis. 1999;19(1):83-92. doi: 10.1055/s-2007-1007100.
The application of gene therapy to liver disease is contingent on the development of an effective gene delivery vehicle. Receptor-mediated endocytosis can be exploited as a means of selective and efficient targeting of gene therapy vectors to hepatocytes. DNA-binding conjugates have been directed to the liver by the attachment of asialoglycoproteins or other ligands for receptors expressed on hepatocytes. Recent studies suggest refinements in this approach through which high transduction rates in vitro may be reproduced in vivo. The intrinsic liver tropism of viral vectors and liposomes can be augmented by the addition of targeting features, as demonstrated in animal models. With further modification, such as the incorporation of hepatotropic elements of the hepatitis viruses or lipoproteins, the next generation of delivery systems may achieve efficient, persistent expression of therapeutic genes in a safe and cell type-specific manner.
基因疗法在肝脏疾病中的应用取决于有效的基因传递载体的开发。受体介导的内吞作用可被用作将基因治疗载体选择性且高效地靶向肝细胞的一种手段。通过连接去唾液酸糖蛋白或其他针对肝细胞上表达的受体的配体，DNA结合偶联物已被导向肝脏。最近的研究表明，这种方法有所改进，体外的高转导率可以在体内重现。如在动物模型中所示，通过添加靶向特征可以增强病毒载体和脂质体固有的肝脏嗜性。通过进一步修饰，例如并入肝炎病毒或脂蛋白的嗜肝元件，下一代递送系统可能以安全且细胞类型特异性的方式实现治疗性基因的高效、持续表达。
