Physiological effects of human growth hormone produced after hydrodynamic gene transfer of a plasmid vector containing the human ubiquitin promotor

Physiological effects of human growth hormone produced after hydrodynamic gene transfer of a plasmid vector containing the human ubiquitin promotor
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DOI:
10.1007/s00109-002-0371-1
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发表时间:
2002-10-01
影响因子:
4.7
通讯作者:
Jensen, TG
Jensen, TG
中科院分区:
医学2区
文献类型:
--
作者:
Dagnæs-Hansen, F;Holst, HU;Jensen, TG

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人生长激素(hGH)缺乏导致生长迟缓和身体脂肪分布和丰度,肌肉生长和骨矿化异常。而注射重组hGH可逆转或改善缺乏症症状。以hGH的体内合成为目标的治疗仍然具有相当大的临床意义。流体动力学注射的一个简单的质粒载体含有人泛素启动子和hGH基因,发现导致高和延长的表达,合成的hGH实现在NOD/SCID小鼠和三个不同的近交系的免疫活性小鼠。尽管hGH抗体在免疫活性小鼠中产生,通过体重增加、胰岛素样生长因子I的血清水平增加和内脏重量的相对增加来证明蛋白质的生理作用。非病毒基因治疗可能被视为一种潜在的未来的方式重建hGH表达缺陷的个人。
Human growth hormone (hGH) deficiency causes retarded growth and abnormalities in body fat distribution and abundance, muscle growth, and bone mineralization. While injection of recombinant hGH may reverse or ameliorate symptoms of deficiency. therapy aiming, at in vivo synthesis of hGH is still of considerable clinical interest. Hydrodynamic injection of a simple plasmid vector containing a human ubiquitin promotor and the hGH gene were found to result in high and prolonged expression, Synthesis of hGH was achieved both in NOD/SCID mice and in three different inbred strains of immune competent mice. Although hGH antibodies were produced in immunocompetent mice., physiological effects of the protein were documented by increase in body weight, increased serum levels of insulin-like growth factor I and relative increased weight of the internal organs. Nonviral gene therapy may be regarded as a potential future way of reconstituting hGH expression in deficient individuals.