LONG-TERM IMPROVEMENT OF HYPERCHOLESTEROLEMIA AFTER EXVIVO GENE-THERAPY IN LDLR-DEFICIENT RABBITS
LONG-TERM IMPROVEMENT OF HYPERCHOLESTEROLEMIA AFTER EXVIVO GENE-THERAPY IN LDLR-DEFICIENT RABBITS
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DOI：
10.1126/science.1722351
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发表时间：
1991-12-20
期刊：
影响因子：
56.9
通讯作者：
WILSON, JM
中科院分区：
文献类型：
--
作者：
CHOWDHURY, JR;GROSSMAN, M;WILSON, JM
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 动物模型（渡边遗传性高脂血症兔）被用来开发一种基于自体肝细胞移植的肝脏定向基因治疗方法，这些肝细胞在体外用重组逆转录病毒进行了基因校正。移植了 LDLR 转导的自体肝细胞的动物表现出血清总胆固醇下降了 30% 至 50%，这种下降在实验期间（122 天）持续存在。从移植后长达 6.5 个月内没有减少的组织中收获重组衍生的 LDLR RNA。
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.