Wilson J M, Grossman M, Wu C H, Chowdhury N R, Wu G Y, Chowdhury J R
Department of Internal Medicine, Howard Hughes Medical Institute, University of Michigan Medical School, Ann Arbor 48109-0650.
J Biol Chem. 1992 Jan 15;267(2):963-7.
Familial hypercholesterolemia is an inherited disease in humans, caused by a deficiency of low density lipoprotein (LDL) receptors, that we have used as a model for developing liver-directed gene therapies. Our strategy is to reconstitute hepatic LDL receptor expression in vivo by administering a DNA-protein complex that is capable of targeting the delivery of functional LDL receptor genes to hepatocytes. Infusion of this DNA-protein complex into the peripheral circulation of a rabbit animal model for familial hypercholesterolemia resulted in hepatocyte-specific gene transfer and a temporary amelioration of hypercholesterolemia. This noninvasive approach to gene therapy should have applications in the treatment of a wide spectrum of human diseases.
家族性高胆固醇血症是一种人类遗传性疾病，由低密度脂蛋白（LDL）受体缺乏引起，我们已将其用作开发肝脏定向基因治疗的模型。我们的策略是通过给予一种能够将功能性LDL受体基因靶向递送至肝细胞的DNA-蛋白质复合物，在体内重建肝脏LDL受体表达。将这种DNA-蛋白质复合物注入家族性高胆固醇血症兔动物模型的外周循环中，导致了肝细胞特异性基因转移以及高胆固醇血症的暂时改善。这种非侵入性基因治疗方法应可应用于多种人类疾病的治疗。
