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High expression of human clotting factor IX cDNA in the bone marrow stroma cells of hemophilia B patient

机译:血友病B患者骨髓基质细胞中人凝血因子IX cDNA的高表达

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摘要

Hemophilia B, a serious bleeding disorder, is an inherited X chromosome-linked disease caused by the deficiency or inactiveness of human clotting factor IX (FIX). The convenr tional clinical treatment of plasma infusion is expensive and associated with a high risk of infection with HIV and herpes virus. In 1987, Anson et al. first transduced human FIX cDNA into rat and human skin fibroblasts and advanced the idea of gene therapy for hemophilia B. Recently, FIX cDNA has been expressed in skin fibroblasts, myoblasts, hepatocytes, endothelial cells and keratocytes at different expression levels (see table 1), in which the clinical trial of gene therapy for hemophilia B using autologous skin fibroblasts method by Xue et al. has achieved an efficient, safe and feasible result. In order to increase the expression level of FIX and search for an alternative new target cell, we first selected bone marrow stroma cells (BMS) of hemophilia B patient as target cells and transduced a new-constructed retroviral vector LNCIX into them, Gene-modified BMS cells can secrete active FIX proteins at the level of (5 6±0.8) mu g/10~6 cells/24h. This study provides a simple and promising way of gene therapy for hemophilia B.
机译:B型血友病是一种严重的出血性疾病,是一种由人类凝血因子IX(FIX)缺乏或缺乏活动引起的遗传性X染色体相关疾病。血浆输注的常规临床治疗是昂贵的并且与HIV和疱疹病毒感染的高风险有关。 1987年,Anson等人。首先将人类FIX cDNA转导到大鼠和人类皮肤成纤维细胞中,并提出了针对血友病B的基因疗法。最近,FIX cDNA已在皮肤成纤维细胞,成肌细胞,肝细胞,内皮细胞和角化细胞中以不同的表达水平表达(见表1)。 ,其中薛等人采用自体皮肤成纤维细胞方法进行血友病B基因治疗的临床试验。取得了高效,安全,可行的结果。为了提高FIX的表达水平并寻找其他新的靶细胞,我们首先选择了血友病B患者的骨髓基质细胞(BMS)作为靶细胞,并向其中转导了新构建的逆转录病毒载体LNCIX,进行了基因修饰BMS细胞可以以(5 6±0.8)μg / 10〜6细胞/ 24h的水平分泌活性FIX蛋白。这项研究为乙型血友病提供了一种简单而有希望的基因治疗方法。

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