Successful ex vivo gene therapy directed to liver in a patient with familial hypercholesterolaemia
Successful ex vivo gene therapy directed to liver in a patient with familial hypercholesterolaemia
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成功针对家族性高胆固醇血症患者肝脏进行离体基因治疗
作者：
M. Grossman;S. Raper;Karen Kozarsky;E. Stein;J. Engelhardt;D. Muller;P. Lupien;James M. Wilson
已经开发了一种用于家族性高胆固醇血症（FH）的基因治疗的离体方法，其中受体移植有用携带LDL受体的重组逆转录病毒遗传校正的自体肝细胞。我们描述了一个29岁的纯合子FH女性的治疗，通过体外基因治疗直接到肝脏。她对这些程序耐受良好，治疗后4个月肝组织的原位杂交显示了转基因表达细胞植入的证据。患者的LDL/HDL比率从基因治疗前的10-13下降到基因治疗后的5-8，这种改善在治疗期间（18个月）保持稳定。这代表了人类基因治疗的第一份报告，其中已经实现了治疗终点的稳定校正。
An ex vivo approach to gene therapy for familial hypercholesterolaemia (FH) has been developed in which the recipient is transplanted with autologous hepatocytes that are genetically corrected with recombinant retroviruses carrying the LDL receptor. We describe the treatment of a 29 year old woman with homozygous FH by ex vivo gene therapy directed to liver. She tolerated the procedures well and in situ hybridization of liver tissue four months after therapy revealed evidence for engraftment of transgene expressing cells. The patient's LDL/HDL ratio declined from 10–13 before gene therapy to 5–8 following gene therapy, improvements which have remained stable for the duration of the treatment (18 months). This represents the first report of human gene therapy in which stable correction of a therapeutic endpoint has been achieved.
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影响因子：
56.9
作者：
BROWN, MS;GOLDSTEIN, JL
通讯作者：
GOLDSTEIN, JL
逆转录病毒载体转导的低密度脂蛋白受体活性的转录后调节。
影响因子：
6.5
作者：
Sharkey,MF;Miyanohara,A;Elam,RL;Friedmann,T;Witztum,JL
通讯作者：
Witztum,JL
影响因子：
56.9
作者：
CHOWDHURY, JR;GROSSMAN, M;WILSON, JM
通讯作者：
WILSON, JM
通过逆转录病毒介导的基因转移在兔肝细胞中表达人因子 IX：血友病 B 基因治疗的潜力。
DOI：
10.1073/pnas.87.16.6141
发表时间：
1990
影响因子：
11.1
作者：
Armentano,D;Thompson,AR;Darlington,G;Woo,SL
通讯作者：
Woo,SL