Chowdhury J R, Grossman M, Gupta S, Chowdhury N R, Baker J R, Wilson J M
Department of Internal Medicine, Albert Einstein College of Medicine, Bronx, NY 10461.
Science. 1991 Dec 20;254(5039):1802-5. doi: 10.1126/science.1722351.
Familial hypercholesterolemia (FH) is an inherited disorder in humans that is caused by a deficiency of low density lipoprotein receptors (LDLRs). An animal model for FH, the Watanabe Heritable Hyperlipidemic rabbit, was used to develop an approach for liver-directed gene therapy based on transplantation of autologous hepatocytes that were genetically corrected ex vivo with recombinant retroviruses. Animals transplanted with LDLR-transduced autologous hepatocytes demonstrated a 30 to 50 percent decrease in total serum cholesterol that persisted for the duration of the experiment (122 days). Recombinant-derived LDLR RNA was harvested from tissues with no diminution for up to 6.5 months after transplantation.
家族性高胆固醇血症（FH）是一种人类遗传性疾病，由低密度脂蛋白受体（LDLR）缺乏引起。FH的动物模型——渡边遗传性高脂血症兔，被用于开发一种基于自体肝细胞移植的肝脏定向基因治疗方法，这些自体肝细胞在体外经重组逆转录病毒基因校正。移植了转导LDLR的自体肝细胞的动物，其血清总胆固醇降低了30%至50%，且在实验持续时间（122天）内一直保持。移植后长达6.5个月，从组织中收获的重组衍生LDLR RNA没有减少。
