Efficient expression of retroviral vector-transduced human low density lipoprotein (LDL) receptor in LDL receptor-deficient rabbit fibroblasts in vitro.
Efficient expression of retroviral vector-transduced human low density lipoprotein (LDL) receptor in LDL receptor-deficient rabbit fibroblasts in vitro.
复制标题
逆转录病毒载体转导的人低密度脂蛋白 (LDL) 受体在 LDL 受体缺陷的兔成纤维细胞中的体外高效表达。
DOI：
10.1073/pnas.85.17.6538
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发表时间：
1988
影响因子：
11.1
通讯作者：
Friedmann,T
中科院分区：
文献类型：
--
作者：
Miyanohara,A;Sharkey,MF;Witztum,JL;Steinberg,D;Friedmann,T
家族性高胆固醇血症是由低密度脂蛋白（LDL）受体遗传缺陷引起的。渡边遗传性高脂血症 (WHHL) 兔也存在 LDL 受体活性缺陷，为纯合子家族性高胆固醇血症提供了极好的动物模型。作为开发家族性高胆固醇血症有效基因疗法的一步，我们构建了一种可传播的逆转录病毒载体，其中含有 LDL 受体的全长人类 cDNA。 RNA 和配体印迹研究表明，体外感染的 WHHL 成纤维细胞有效表达人类受体。受感染的成纤维细胞结合并降解人类 LDL 受体 (IgGC7) 特异性的单克隆抗体，其方式与正常人类成纤维细胞类似。人类 LDL 也会被受感染的 WHHL 细胞降解，并促进胆固醇酯化，其程度与正常人成纤维细胞中所见的程度相同。尽管技术问题仍有待解决，但这些研究表明，原则上，基因治疗对于家族性高胆固醇血症患者是可能的。
Familial hypercholesterolemia is caused by a genetic deficiency of the low density lipoprotein (LDL) receptor. The Watanabe heritable hyperlipidemic (WHHL) rabbit, which is also defective in LDL receptor activity, provides an excellent animal model of homozygous familial hypercholesterolemia. As a step toward development of effective gene therapy for familial hypercholesterolemia, we have constructed a transmissible retroviral vector containing a full-length human cDNA for the LDL receptor. WHHL fibroblasts infected in vitro expressed the human receptor efficiently, as indicated by RNA and ligand blotting studies. Infected fibroblasts bound and degraded a monoclonal antibody specific for the human LDL receptor (IgGC7) in a manner comparable to that seen with normal human fibroblasts. Human LDL was also degraded by infected WHHL cells and promoted cholesterol esterification to the same degree as seen in normal human fibroblasts. Although technical problems remain to be solved, these studies show that, in principle, gene therapy may be possible for familial hypercholesterolemia patients.
影响因子：
4.3
作者：
H. Sambrook
通讯作者：
H. Sambrook